PMID- 11979211
TI  - An exploration of district nurses' perception of occupational stress.
AB  - Many studies in nurse occupational stress have been carried out on high
      dependency areas in general nursing, while community nursing has been neglected.
      District nurses, however, appear to be under increasing pressure, especially in
      the light of recent NHS reforms. This study aimed to explore district nurses'
      experiences in relation to the range and severity of stressful work-related
      events encountered in district nursing practice. The study was undertaken in a
      Yorkshire community healthcare NHS trust, with a convenience sample of 50
      qualified district nurses, of which 38 successfully completed the questionnaire.
      The sample included F, G and H grade levels working both full-time and part-time.
      The research design adopted was a descriptive, non-experimental cross-sectional
      survey, integrating quantitative and qualitative approaches. Data were collected
      using the Community Health Nurses' Perceptions of Work-Related Stressors
      Questionnaire (Walcott-McQuigg and Ervin, 1992). Results revealed that the most
      stressful aspects of work for this group of district nurses were: work overload;
      climate of change; nursing patients with complex care needs; lack of teamwork
      with other departments, and family responsibilities (home/work interface).
      Results were consistent with much of the evidence reported in the literature,
      demonstrating that district nurses are a comparatively stressed group of
      healthcare professionals.

PMID- 11979212
TI  - Hospitals are to be given standards of cleanliness.

PMID- 11979213
TI  - Good employment practice will make nurses feel valued.

PMID- 11979214
TI  - The role of nurses with regard to health and safety at work.

PMID- 11979215
TI  - School nurse who formed sexual relationships with boys.

PMID- 11979216
TI  - Nursing care of patients with nasogastric feeding tubes.
AB  - Nasogastric tubes are commonly used for patients as a short-term method of
      providing continuous, pre-packed liquid feed. In order to explore how evidence
      based practice is being incorporated into care, we conducted a survey
      investigating the views and practices of nutrition specialist nurses in acute
      trusts across the UK. A postal questionnaire comprising 35 questions considered
      the role of the nutrition specialist nurse, care of patients with nasogastric
      tubes, and training and education of nurses in the care of these patients.
      Results of this small study indicate differences in the education and practice of
      nursing care for patients with nasogastric tubes. Therefore, it is vital that
      evidence and good practice is disseminated both locally and nationally by
      benchmarking practice and by sharing knowledge and experiences in both journals
      and conferences. Nurses also need support in practising their skills to ensure
      they feel confident in caring for patients with nasogastric tubes.

PMID- 11979217
TI  - Development of a screening tool to assess risk of tardive dyskinesia.
AB  - This article gives an overview of antipsychotic medication and of tardive
      dyskinesia (TD). It examines the research available on TD as it relates to people
      with a learning disability (PWLD). The evidence identifies that specific groups
      of people are at an increased risk of developing TD. It also shows that 45-50% of
      PWLD who are treated with antipsychotic medication will be affected by TD. The
      evidence is used in the formulation of an assessment tool designed for use by the
      community learning disability nurse to identify an individual's risk of
      developing TD before commencing medication. Litigation in the USA has led to a
      $6.7 m award for sound, clinically effective practice and evidence-based
      interventions requires that practitioners are accountable for their practice, but
      are also seen to transform existing services in a way which improves the delivery
      of quality interventions and care.

PMID- 11979218
TI  - The treatment and diagnosis of non-epileptic attack disorder.
AB  - Epilepsy is the most common serious neurological condition in the UK with a
      lifetime prevalence of 2-5% of the population. Epilepsy is also common in the
      learning disability population. As many as 36% of patients diagnosed with
      epilepsy may have 'pseudoepileptic' episodes instead of, or as well as, true
      epileptic attacks. This article explains how the diagnosis of non-epileptic
      attack disorder is made and identifies some of the difficulties inherent in
      diagnosing and treating this disorder. The costs of failing to recognize the
      condition are illustrated in a case study that also demonstrates the
      effectiveness of the interventions of a specialist epilepsy nurse in terms of
      health and economic gains and is an example of the benefits of effective
      multidisciplinary teamwork.

PMID- 11979219
TI  - Lymphoedema 2: classification, signs, symptoms and diagnosis.
AB  - The second article in this series describes the different types of lymphoedema
      and the signs and symptoms associated with the condition. In the preceding
      article (Vol 11(5): 304-9) we examined the anatomy, physiology and functions of
      the lympathic system in relation to the condition of lymphoedema, and
      demonstrated how, by acting as a one-way drainage system, the lympathics maintain
      tissue homeostasis through the removal of excess fluid from the interstitial
      spaces. Failure or dysfunction of the system can result in lymphoedema, a
      condition characterized by the accumulation of fluid in the soft tissues.
      Lymphoedema is classified into two main groups - primary and secondary. Defining
      the causative factors and pathogenesis of both conditions and other forms of
      chronic oedema will assist the reader in the clarification of the condition. The
      article concludes with an overview of assessment criteria for diagnosis, which
      should assist all healthcare professionals in appropriate referral. The third
      article in this series will look at the treatment of lymphoedema.

PMID- 11979220
TI  - Statutory provisions of the Health and Safety at Work Act 1974.
AB  - Case Scenario: Rose is working as a staff nurse in the operating theatre of Roger
      Park Hospital when there is an explosion. She is severely burnt. Following an
      inspection by the Health and Safety Inspectorate, the Roger Park NHS Trust is
      informed that it will be prosecuted. It appears that the cause of the explosions
      was the result of gases igniting because of an electrical fault in a patient
      monitor.

PMID- 11979221
TI  - Actico: a short-stretch bandage in venous leg ulcer management.
AB  - Actico compression bandage system (Activa Healthcare) completes the prevention
      and treatment regime of venous leg ulcer management. Actico gives the patient
      comfort by being a simple two-layer compression bandage system that is also
      effective and which stays in place because of its cohesive nature. This product
      focus looks at the impact of venous leg ulcers, the use of compression and
      focuses on short-stretch bandages and the Actico bandage system.

PMID- 11979222
TI  - Patient comfort rounds: a new initiative in nursing.

PMID- 11979223
TI  - [Diagnosis of thrombo-embolic disorders: is there a clear and effective strategy
      available?].

PMID- 11979224
TI  - [When the pituitary swells up a little].

PMID- 11979225
TI  - [Prenatal diagnosis of isolated posterior fossa anomalies: attempt at a
      simplified approach].
AB  - The authors suggest, after some embryological, anatomical and nosological
      reviews, a simplified approach mainly based on the appearance of the pons,
      cerebellar hemispheres and vermis, independently from an associated cystic
      dilatation of the posterior fossa. Pontocerebellar hypoplasias and partial or
      total vermian agenesis are detailed because they can be diagnosed with a prenatal
      MRI. This classification based on our experience and on the literature data
      should be of value to evaluate the neurological prognosis.

PMID- 11979226
TI  - [Pituitary adenomas and pregnancy: morphological MRI features].
AB  - The authors present the clinical aspects and changes of the pituitary gland and
      adenomas in pregnant women by MRI. A number of physiological morphologic changes
      are seen during pregnancy. Moreover, the hormonal milieu affects patients with
      adenomas which could evolve leading to severe complications as hypertrophy,
      necrosis, and hemorrhage. An increase in the volume and T1 hyperintensity of the
      anterior pituitary, is normally seen. These changes are explained by an increase
      in lactotrops and prolactin production. Tumoral complications are more frequent
      with macroadenomas, and are suggestive of a sellar mass or apoplexy.
      Nevertheless, other differential diagnoses must be suggested in pregnancy and
      post-partum including hypophysitis and Sheehan syndrome.

PMID- 11979227
TI  - [D-Dimer determination combined with clinical probability for the diagnosis of
      leg venous thrombosis].
AB  - OBJECTIVE: To evaluate the results of combination of D-Dimer test and simple
      clinical model for the diagnosis of deep vein thrombosis (DVT). MATERIALS AND
      METHODS: Inclusion: clinical suspicion of DVT. Non inclusion criteria were
      Clinical model performed by the referring physician included probability varying
      from high to low. D-Dimer test was performed by five different rapid techniques.
      Standard of reference was Doppler ultrasonography (DU) performed by a senior
      radiologist. RESULTS: Eight hundred and fifty-four DU were performed on a 14
      months time period, including 206 suspicion of pulmonary embolism, 109
      postoperative time period, 120 non-included or excluded patients, 278 incomplete
      observations, 141 complete observations. DVT was present in 33 cases and absent
      in the other 108 cases (prevalence 23%). Sensitivity and negative predictive
      value of the five tests were between 82 and 97% and 90 et 97%. The most sensitive
      test had a specificity of 36% and a positive predictive value of 32%. Combination
      of clinical model and D-Dimer test did not improve the diagnostic accuracy.
      CONCLUSION: None of the test evaluated in the present study, even when combined
      with the clinical model results, did allow the exclusion of DVT.

PMID- 11979228
TI  - [MRI of portal cavernoma with biliary involvement].
AB  - PURPOSE: To assess the value of MRI in the diagnosis of portal cavernoma with
      biliary obstruction. MATERIAL: and methods: six patients referred for clinical
      suspicion of biliary obstruction and portal cavernoma were explored with MRI. all
      patients were explored using a signa 1.5 t GE MR unit, with high gradient field
      strength and torso phased array coil. Biliary ducts were explored with ss-fse
      sequences of MR-cholangiopancreatography (MRCP), coronal and oblique coronal 20mm
      thick slices. Then, coronal T2w with shorter TE eff, MR-angiography and delayed
      T1w sequences were performed. CT scan and sonographic examinations of the liver
      were performed in all patients. Two patients were operated on and 2 underwent
      endoscopic retrograde cholangiography. RESULTS: Three different types of biliary
      involvement were found: in 3 cases findings that mimic cholangiocarcinoma
      spreading along the common bile duct and in 3 other cases multiple smooth
      extrinsic impressions along the common bile duct; in one patient MRCP
      demonstrated an irregular narrowing of the common bile duct mimicking chronic
      cholangitis. In all cases, the bile duct varices appeared of low T2W signal; in
      three cases, fibrosis was identified on delayed sequences. CONCLUSION: MRCP and
      MR-angiography can be proposed as a first imaging study in patients with portal
      cavernoma and cholestasis or bile duct dilatation.

PMID- 11979229
TI  - [Infection control in interventional radiology: good practice guideline].
AB  - PURPOSE: In 1997, two studies were performed in interventional radiology units,
      one of them by the CCLIN Paris-Nord and the other, by the staff of the vascular
      radiology department of Hautepierre Hospital of Strasbourg in collaboration with
      the CCLIN Est. The results have shown poor compliance with recommended infection
      control guidelines and standard precautions. A working group was set up by the
      CCLIN Paris-Nord, with radiologists, radiology technicians, nurses and infection
      control practitioners to elaborate guidelines for infection control practices in
      interventional radiology. Materials and methods. These guidelines were compiled
      using legislation, consensus or expert conferences, evaluations or studies which
      had demonstrated a benefit to prevent infectious risk. The working group also
      formulated its own recommendations when no pre-existing document was available.
      These recommendations have been categorized according to evidence of benefit in
      infectious risk prevention. RESULTS: Guidelines are divided in two parts. The
      first part describes rooms and optimal architecture of the interventional
      radiology unit, flows (patients, staff, material, linen and waste), type of floor
      and furniture surfaces, and environment of the interventional unit (air, water,
      room and device cleaning). The second part details staff garments, hand washing
      procedures according to tasks, and protection against accident for the staff
      (accidental blood exposure, antimitotic drugs). Recommendations have been
      elaborated for patients'skin preparation and equipment handling (contrast
      product, automatic injector, US, scanner). A proposal for work organization is
      made regarding nursing protocols, documents of maintenance, surveillance of
      medical devices.

PMID- 11979230
TI  - [Features of hysterosalpingography performed in Burkina Faso].
AB  - PURPOSE: The goal of this study was to describe the distinctive
      hysterosalpingographic features of women with infertility in Burkina Faso.
      MATERIALS AND METHODS: We performed a retrospective study of 1019 women who were
      referred for infertility between January 1996 to June 1997 at the National
      Hospital Centre of Ouagadougou. Clinical and radiological features were reviewed
      and statistical data analysed on the software EPI Info 5.0. RESULTS: The mean age
      of the patients was 28+/-0,3 years. Primary infertility was found in 34.4% and
      secondary infertility in 65.6%. Abnormalities on plain film were present in 6.9%
      of the cases. Hysterosalpingography was abnormal in 62.1% of the cases. Tubal
      abnormalities were found in 62% and uterine lesions in 38.3%. The main
      hysterosalpingographic abnormalities were tubal obstructions, hydrosalpinx,
      uterine fibromas, and trauma sequelae in 25,9%, 25,3%, 16,5% and 10% of cases
      respectively. Seventy one percent of tubal and uterine lesions represent outcomes
      of chronic infections and underground abortions. CONCLUSION: In Burkina Faso,
      hysterosalpingographic abnormalities are characterized by the predominance of
      infectious and traumatic sequelae. Such a frequency could be reduced by active
      politics against underground abortion and information about genital infections.

PMID- 11979231
TI  - [Tuberculous meningitis: value of neuro-imaging for early diagnosis].
AB  - The authors report a case of tuberculous meningoencephalitis diagnosed in a 20
      month-old boy with severe neurological sequelae. Most cases of the tuberculous
      meningitis occur in children less than 3 years old. The mortality rate and
      incidence of sequelae are greater without early treatment. Imaging has a great
      impact in the early diagnosis of this disease. In Europe, the increasing
      incidence of tuberculosis underscores the need to diagnose tuberculous meningitis
      without delay in children in order to provide a prompt and appropriate treatment.

PMID- 11979232
TI  - [Miliary induced by intravesical BCG immunotherapy for carcinoma of the bladder:
      CT Findings].
AB  - The authors describe the case of a patient presenting miliary involvement of the
      lung due to mycobacterium bovis after intravesical BCG administration. After
      initial transurethral resection, the patient was treated with immunotherapy by
      intravesical instillation of BCG and received 9 treatments without any problem.
      After the 10th treatment, the patient presented with cough and signs of urinary
      infection. At admission the chest radiograph showed a miliary pattern, better
      seen at high resolution CT, and using helical technique with the maximum
      intensity projection (MIP) reconstructions. MIP demonstrated to better advantage
      the well defined contours of the nodules, distributed evenly and randomly in the
      whole lung. After anti-TB treatment, the patient had regained full activity with
      persistence of the miliary pattern but a decreased number and size of nodules and
      calcification in some of them. This case illustrates a rare complication of
      intravesical immunotherapy, and points out the superiority of Sliding Thin Slab
      MIP (STS-MIP) compared with standard HRCT which allows a better detection of
      extent and follow-up of a military pattern, notably in moderate forms, by
      improvement of the anatomical resolution.

PMID- 11979233
TI  - [Giant hydropic fibroma: a case report].
AB  - Hydropic degeneration of a uterine leiomyoma is common. Giant forms are uncommon.
      Positive diagnosis may be challenging because the differential diagnosis includes
      other rare uterine tumors such as leiomyosarcoma. Uterine localization, the
      leiomyoma volume, margins with adjacent structures are best evaluated at MRI.
      Final diagnosis requires gross and microscopic examination. We describe such a
      diagnostic challenge in a 46-year-old woman with a giant hydropic leiomyoma.

PMID- 11979234
TI  - [An asymptomatic aneurysm of the popliteal artery treated with endoprosthesis].
AB  - Stent-graft is considered as a possible alternative to traditional surgery in the
      correction of popliteal aneurysms but only a few cases have been reported and
      these are difficult to compare. This new case highlights the feasibility and
      problems of an endovascular approach. The size of the stent was determined on the
      basis of preliminary arterial scanning and a measurement guide wire. Strong
      recommendations to the patient to avoid posture-related kinking of the artery
      and/or the stent (during occupation-related or other activities) could prevent
      delayed thrombosis of the stent. The lifetime of the stent can be prolonged by a
      simple radiosurgical clearance procedure.

PMID- 11979235
TI  - [Quid? Retroperitoneal duodenal traumatic perforation].

PMID- 11979236
TI  - Differential expression of cone opsin mRNA levels following experimental retinal
      detachment and reattachment.
AB  - PURPOSE: To identify changes in S- and M-sensitive cone opsin gene expression
      following retinal detachment (RD) and reattachment. METHODS: Cat retinas were
      detached for 1, 3, 7, or 28 days, or reattached after 1 h, 1 day, or 3 days of RD
      and fixed in 4% paraformaldehyde. Pieces of mid-peripheral retina were removed
      from the same region of each detached, normal (attached), and reattached retina
      and embedded in paraffin. Paraffin sections (8 mm) were processed for in situ
      hybridization using S- or M-cone opsins, rod opsin, or phosducin riboprobes in
      vitro transcribed from cat partial cDNAs. Labeled cells were counted to obtain
      the number of labeled cells/mm retina. RESULTS: The number of cells labeled with
      the anti-sense cone opsin riboprobes, and the intensity of this label, decreased
      after RD. The number of cones labeled with the anti-sense S-opsin riboprobe
      decreased to 42% of normal at 3 days of RD. The number of M-opsin mRNA-positive
      cones decreased to 4% of normal at 3 days of RD. The number of cells positive for
      M-opsin or S-opsin mRNA recovered to near normal levels after reattachment.
      Phosducin and rod opsin mRNA labeling was near normal in surviving rod
      photoreceptors after RD. CONCLUSIONS: Cones and rods behave differently after
      detachment. There are significant obstacles to overcome in order to study the
      responses of cones after RD because surviving cells no longer label with
      antibodies used as cone markers in normal retina. The results of this study show
      that: (1) After RD, surviving cones decrease their expression of opsin mRNA while
      rods do not; (2) Upon reattachment of the retina, the cones once again begin to
      express their opsins; (3) Most cones survive short-term detachments; and (4)
      Defects in cone-based vision after reattachment may not be based mainly on the
      loss of cones but due to other changes in these cells, for example, reduced
      phototransduction and/or changes in synaptic connectivity to second order
      neurons.

PMID- 11979238
TI  - Tricuspid valve disease: tricuspid valve complex perspective.

PMID- 11979237
TI  - Macrophage and retinal pigment epithelium expression of angiogenic cytokines in
      choroidal neovascularization.
AB  - PURPOSE: To determine the expression of angiogenic cytokines in macrophages and
      retinal pigment epithelium cells in choroidal neovascularization (CNV). METHODS:
      Ten surgically-excised subfoveal CNV specimens and ten eye bank eyes with
      subfoveal CNV were routinely processed, serially sectioned, and immunostained for
      factor VIII (F8), CD68 (KP1), cytokeratin 18 (CK18), vascular endothelial growth
      factor (VEGF), tissue factor (TF), and monocyte chemotactic protein (MCP). The
      CNV was classified as "inflammatory active" (more inflammation than fibrosis) or
      "inflammatory inactive" (morefibrosis than inflammation). The immunostaining was
      graded as none, mild (+), moderate (++), or heavy (+++). Five additional
      surgically-excised CNV specimens were dual labeled with CK18/MCP or CD68/TF and
      confocal scanning laser microscopy was performed. RESULTS: Vascular endothelium,
      macrophages, and RPE expressed F8, KP1, and CK18 respectively. Macrophages
      expressed + to ++ VEGF and ++ to +++ TF; RPE expressed ++ to +++ VEGF and ++ to
      +++ MCP. Staining for angiogenic cytokines was stronger in inflammatory active
      versus inflammatory inactive CNV. RPE dual labeled for CK18/MCP and macrophages
      dual labeled for CD68/TF. CONCLUSIONS: This study shows that RPE cells express
      MCP, a cytokine involved with macrophage recruitment, and that macrophages
      express TF in CNV. Macrophages and RPE express VEGF, thus perpetuating
      angiogenesis. TF is involved with fibrin formation and provides a scaffold effect
      for growth of the CNV complex. CNV likely represents a dynamic process with
      inflammatory active and inflammatory inactive (involutional) stages.

PMID- 11979239
TI  - A prospective, randomized trial of large- versus small-volume endoscopic
      injection of epinephrine for peptic ulcer bleeding.
AB  - BACKGROUND: Endoscopic injection of epinephrine in the treatment of bleeding
      peptic ulcer is considered highly effective, safe, inexpensive, and easy to use.
      However, bleeding recurs in 6% to 36% of patients. The aim of this study was to
      determine the optimal dose of epinephrine for endoscopic injection in the
      treatment of patients with bleeding peptic ulcer. METHODS: One hundred fifty-six
      patients with active bleeding or nonbleeding visible vessels were randomized to
      receive small- (5-10 mL) or large-volume (13-20 mL) injections of a 1:10,000
      solution of epinephrine. RESULTS: The mean volume of epinephrine injected was
      16.5 mL (95% CI [15.7, 17.3 mL]) in the large-volume group and 8.0 mL (95% CI
      [7.5, 8.4 mL]) in the small-volume group. Initial hemostasis was achieved in all
      patients studied. The number of episodes of recurrent bleeding was smaller in the
      large-volume group (12/78, 15.4%) compared with the small-volume group (24/78,
      30.8%, p = 0.037). The volume of blood transfused after entry into the study,
      duration of hospital stay, numbers of patients requiring urgent surgery, and
      mortality rates were not statistically different between the 2 groups.
      CONCLUSIONS: Injection of a large volume (>13 mL) of epinephrine can reduce the
      rate of recurrent bleeding in patients with high-risk peptic ulcer and is
      superior to injection of lesser volumes of epinephrine when used to achieve
      sustained hemostasis.

PMID- 11979240
TI  - Patient tolerance and acceptance of unsedated ultrathin esophagoscopy.
AB  - BACKGROUND: Unsedated endoscopy has not gained wide acceptance in the United
      States. Factors that may predict tolerance and acceptance of unsedated endoscopy
      are ill defined. METHODS: Outpatients referred for standard EGD were recruited to
      undergo unsedated ultrathin esophagoscopy (UUE) with a new 3.1-mm battery-powered
      esophagoscope before sedated EGD. They rated preprocedure and postprocedure
      anxiety levels with the Profile of Mood States Tension/Anxiety subscale (POMS-SF
      T/A). They also rated symptoms and overall acceptability and listed procedural
      preference between EGD and UUE. Patients who refused UUE noted a reason for
      refusal and also completed the anxiety questionnaire. RESULTS: Fifty-two of 98
      patients recruited agreed to participate, and underwent both UUE and EGD.
      Patients who refused UUE were significantly more anxious (mean anxiety score, 8.2
      vs. 4.5, p < 0.005). Participants reported no significant difference between
      preprocedural (4.6 vs. 5.3) or postprocedural (3.5 vs. 2.6) anxiety for UUE
      versus standard EGD. After undergoing both procedures, only 46% stated they would
      prefer UUE to EGD in the future. Patients who chose the peroral approach were
      more likely to prefer UUE than those who chose the transnasal approach (58% vs.
      23%, p = 0.02). CONCLUSIONS: Patient acceptance of unsedated endoscopy even with
      an ultrathin instrument is limited. Anxiety assessment by the POMS-SF T/A can
      identify patients willing to undergo UUE. Patients who choose transoral UUE may
      be more willing to repeat the procedure.

PMID- 11979241
TI  - Unsedated upper endoscopy in children.
AB  - BACKGROUND: EGD is essential to the investigation and treatment of GI disorders
      in children. Although safe, EGD has the potential for complications, in
      particular cardiopulmonary abnormalities associated with intravenous sedation.
      EGD is often performed in adults without sedation. Unsedated EGD is occasionally
      performed in children but has not been subjected to study. This study assessed
      the safety, efficacy, and feasibility of unsedated EGD in children. METHODS:
      Selected, highly motivated children requiring EGD were offered the choice of
      sedation or no sedation for the procedure. Children recorded scores for pain
      (face scale) and anxiety (vertical visual analogue scale) before and after EGD.
      In addition, the times required to prepare the patient, perform the EGD, and
      recover the patient were recorded. RESULTS: There was no difference in age,
      gender, or pre-EGD pain scores between children selecting sedation or no
      sedation. However, children selecting sedation had significantly higher pre-EGD
      anxiety scores than those who chose no sedation. Successful completion of EGD was
      similar for sedated (96.3%) and unsedated (95.2%) children. Post-EGD scores for
      anxiety were significantly decreased in those receiving sedation and unchanged in
      children who received no sedation. There was no significant change in post-EGD
      pain score in either group. Nearly 80% of children undergoing unsedated EGD would
      elect to forego sedation if EGD was needed again. Total procedure time was
      significantly longer in sedated versus unsedated children, reflecting longer
      preparation and recovery. CONCLUSIONS: Unsedated EGD can be performed safely and
      successfully in children with good patient tolerance. There was a significant
      decrease in total procedure time for children who have unsedated EGD. Unsedated
      EGD should be considered a viable option for motivated children.

PMID- 11979242
TI  - In vivo characterization of colonic thermal injury caused by argon plasma
      coagulation.
AB  - BACKGROUND: Argon plasma coagulation has been rapidly accepted for endoscopic
      obliteration of vascular lesions and superficial tumors. Depth of injury is
      thought to be limited through preferential discharge of energy to nondesiccated
      tissue. However, argon plasma coagulation-induced injury has not been well
      characterized. The aim of this study was to characterize argon plasma coagulation
      induced colonic injury by using a porcine model. METHODS: Laparotomy was
      performed in 6 female swine and the colon exteriorized with the subjects under
      general anesthesia. Lesions were made with an argon plasma coagulation probe held
      perpendicular and 2 mm from the mucosa. Variables studied were as follows: power
      (45 W, 60 W, and 75 W) and duration (1, 2, or 3 seconds; n = 11 for each
      power/duration combination). Injury was graded as either superficial or deep,
      involving the muscularis propria. RESULTS: Circular muscle layer injury
      correlated closely with power (p = 0.02), duration (p = 0.001), and total energy
      delivered (r = 0.977). Longitudinal muscle damage was associated with duration of
      burn (p = 0.001) and total energy delivered (r = 0.855), but correlated poorly
      with power (p = 0.40). No perforations occurred. Submucosal injection of saline
      solution had a protective effect with reductions in circular (90% to 10%, p =
      0.002) and longitudinal muscle injury (50% to 0%, p = 0.1). CONCLUSIONS: Injury
      to the muscularis propria occurs at recommended settings for argon plasma
      coagulation. Injury correlates with power setting, duration of burn, and total
      energy delivery. Protective arcing to nondesiccated tissue does not appear to be
      significant in vivo. Submucosal injection of saline solution protects against
      deep injury.

PMID- 11979243
TI  - A controlled study of the effect of midazolam on abnormal sphincter of Oddi
      motility.
AB  - BACKGROUND: The effect of a medication on sphincter of Oddi motility should be
      characterized if it is to be used during sphincter of Oddi manometry. Controversy
      exists as to whether midazolam influences sphincter of Oddi motility. This study
      assessed the effect of midazolam on the hypertensive sphincter of Oddi. METHODS:
      The study population consisted of 36 patients who presented with recurrent
      abdominal pain resulting from sphincter of Oddi dysfunction. The study was
      nonrandomized, prospective, and placebo controlled. Patient allocation was
      consecutive. Sphincter of Oddi manometry was performed in standard fashion.
      Manometric tracings were interpreted while the investigator was blinded to
      treatment allocation. Eighteen patients in the test group received 2 mg of
      midazolam intravenously whereas the 18 patients in the control group received
      saline solution intravenously. Manometric parameters were measured before and 3
      minutes after the intravenous infusion. Changes in manometric findings before and
      after the administration of saline solution and midazolam were compared. RESULTS:
      Midazolam caused a significant reduction in basal sphincter of Oddi pressure (24
      mm Hg) as compared with saline solution (p < 0.001). Diagnostic concordance
      (normal vs. abnormal) between the basal sphincter pressure before and after
      midazolam was seen in only 77% of patients. CONCLUSIONS: Midazolam significantly
      altered sphincter of Oddi motility. The decrease in sphincteric pressures would
      have altered diagnosis and management in 4 of 18 patients. Midazolam should not
      be used during sphincter of Oddi manometry.

PMID- 11979244
TI  - Classification of Barrett's epithelium by magnifying endoscopy.
AB  - BACKGROUND: The specialized columnar epithelium of Barrett's esophagus can be
      detected by obtaining random or 4 quadrant biopsy specimens at conventional
      endoscopy. However, little is known about the fine mucosal structure of
      specialized columnar epithelium. METHODS: Thirty patients with Barrett's
      esophagus were studied by magnifying endoscopy. The fine mucosal pattern (pit
      pattern) of 67 regions in Barrett's mucosa was recorded and compared with
      methylene blue staining. Histologic, mucin immunohistologic, and cell
      proliferation analyses of biopsy specimens were performed in relation to the pit
      patterns determined by magnifying endoscopy. RESULTS: Pit pattern was classified
      into 5 types. Tubular and villous pit patterns were not only characteristics of
      both specialized columnar epithelium and methylene blue absorption, but also
      possessed an intestinal mucin phenotype with a high Ki-labeling index, whereas
      other pit patterns (dot and straight) did not have specialized columnar
      epithelium and were categorized as the gastric phenotype. The long oval pit
      pattern had an intermediate phenotype between gastric and intestinal.
      CONCLUSIONS: The classification of the superficial mucosal appearance of
      Barrett's epithelium by magnifying endoscopy reflects not only histologic
      features but also mucin phenotypes.

PMID- 11979246
TI  - Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy
      response in esophageal carcinoma.
AB  - BACKGROUND: EUS-measured reduction in tumor size after neoadjuvant therapy has
      previously been correlated with downstaging and improved survival in patients
      with esophageal cancer. The aim of this study was to determine whether tumor
      changes measured by EUS correspond to pathologically assessed chemoradiotherapy
      induced tumor regression. METHODS: Forty-one patients with esophageal cancer
      treated with combined modality treatment were studied. After initial EUS,
      patients completed a cisplatin/carboplatinum, 5-fluorouracil, and radiotherapy
      regimen and underwent repeat EUS before resection. A positive response on EUS was
      defined as a 50% reduction in maximal tumor cross-sectional area.
      Chemoradiotherapy-induced tumor regression was assessed in resection specimens by
      using a previously defined pathologic scoring system based on the extent of tumor
      proliferation into adjacent fibrosis. RESULTS: Pathologic tumor regression was
      present in 23, indeterminate in 5, and minimal or absent in 13 patients. EUS
      measured a positive response in 20 of 23 (87%) patients with CRT-induced tumor
      regression and a negative response in 10 of 13 (77%) patients with absent tumor
      regression (p < 0.001). EUS had a positive predictive value of 80% for pathologic
      tumor regression. CONCLUSIONS: Measurement of tumor size by EUS is a reliable
      clinical method for assessing pathologic tumor regression before surgery.

PMID- 11979245
TI  - Helical CT versus EUS with fine needle aspiration for celiac nodal assessment in
      patients with esophageal cancer.
AB  - BACKGROUND: Conventional CT is insensitive for detection of metastatic
      involvement of celiac lymph nodes in esophageal cancer. Helical CT has
      theoretical advantages over "slice" CT in this regard, but its performance has
      not yet been prospectively studied. METHODS: Consecutive patients with untreated
      esophageal cancer were recruited after obtaining informed consent. Helical CT was
      performed on all patients and TNM staging was performed by a single radiologist.
      Subsequently, all patients underwent esophageal radial and, as needed,
      curvilinear array EUS with fine needle aspiration (FNA), for evaluation of celiac
      lymph nodes and TNM staging. Test performance characteristics with 95% confidence
      intervals were calculated, assuming EUS with FNA as the reference standard.
      RESULTS: Forty-eight patients were recruited, of whom 37 (77%) were men. The mean
      (SD) age was 63.6 (10) years. Excluding 5 patients in whom a confirmatory FNA was
      not available (n = 43), helical CT identified celiac lymph nodes in 12 (28%)
      patients. The reference standard of EUS with FNA identified 15 (35%) patients
      with metastatic celiac lymph nodes, giving a sensitivity, specificity, and
      positive and negative predictive values for helical CT of 53% (95% CI [28%,
      79%]), 86% (95% CI [73%, 99%]), 67% (95% CI [40%, 93%]), and 77% (95% CI [63%,
      92%]), respectively, for assessing celiac lymph nodal involvement. The
      sensitivity and specificity of helical CT in detecting T4 disease were 25% (95%
      CI [3.8%, 46%]) and 94% (95% CI [85%, 100%]), respectively. There were 12
      patients (25%; 95% CI [13%, 37%]) who were felt to have resectable disease by
      helical CT but had either metastatic involvement of celiac lymph nodes or T4
      disease by EUS/FNA. CONCLUSIONS: Despite technological advances, helical CT still
      appears unreliable, mainly because of insensitivity, for the identification of
      inoperable T4 or metastatic involvement of celiac lymph node disease in
      esophageal cancer.

PMID- 11979247
TI  - Interobserver agreement in staging gastric malt lymphoma by EUS.
AB  - BACKGROUND: EUS is highly accurate for staging gastric lymphoma. Because stage
      correlates to outcome, interobserver agreement is mandatory. However, previous
      studies suggest that interobserver agreement might vary according to T-stage. A
      multicenter evaluation of observer agreement with respect to endosonographic
      staging of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was
      therefore conducted. METHODS: Fifty-four patients were studied; 42 were also
      evaluated after eradication of Helicobacter pylori infection. EUS was performed
      at different institutions by 10 experienced endosonographers who collected the
      best photographs for each examination. Interobserver agreement was estimated with
      kappa statistics. RESULTS: Overall interobserver agreement for T-stage was fair,
      both before and after treatment (kappa = 0.38 and kappa = 0.37, respectively).
      Overall interobserver agreement for N-stage was substantial before treatment, but
      only fair after treatment (kappa = 0.63 and kappa = 0.34, respectively). The
      lowest values of agreement occurred with T1sm (submucosa) and T2 stage lesions.
      CONCLUSIONS: Interobserver agreement for staging of gastric MALT lymphoma by EUS
      is suboptimal before as well as after treatment of H pylori infection. This
      evidence suggests that gastric EUS may be more difficult technically compared
      with EUS of other organs. Lack of agreement is crucial because it influences the
      choice of therapy and assessment of response to treatment. Good interobserver
      agreement would permit better communication concerning the clinical status of
      patients, comparison of the results of different studies, and stratification of
      patients within clinical trials.

PMID- 11979248
TI  - Influence of EUS training and pathology interpretation on accuracy of EUS-guided
      fine needle aspiration of pancreatic masses.
AB  - BACKGROUND: Identification, staging, and fine needle aspiration of pancreatic
      mass lesions are probably the most technically demanding EUS skills. This study
      evaluated the effect of formal training on the diagnostic accuracy of EUS-guided
      fine needle aspiration (EUS-FNA) of pancreatic masses and the source of the
      variability in diagnostic accuracy between initial and later procedures. METHODS:
      Sixty-five patients with pancreatic masses underwent EUS-FNA between April 1998
      (introduction of EUS-FNA) and August 1999, 20 of whom were examined by 3
      endosonographers without prior experience with EUS-FNA. The initial experience of
      these 3 endosonographers (April to December 1998; group A patients), which
      included a formal training period of 2 months, and their later experience
      (January to August 1999; group B patients) were evaluated. Final diagnoses were
      determined by surgical pathology or clinical follow-up. All EUS-FNA samples were
      reviewed by 4 blinded pathologists to determine the contribution of pathologist
      interpretation to varying EUS-FNA accuracy. RESULTS: After a short training
      period, there was a significant improvement in EUS-FNA accuracy (33% vs. 91%; p =
      0.004). After pathology review, good agreement was identified between original
      FNA interpretation and that on review (kappa = 0.78; 95% CI [0.5, 1.0]). There
      were differences between the mean cellularity score (2.8 vs. 1.8, p = 0.01) and
      mean number of passes (5.1 vs. 2.8, not significant) for correct versus incorrect
      FNA specimens. CONCLUSION: Significant improvements in EUS-FNA accuracy can be
      achieved with a short period of mentored training. EUS-FNA errors during the
      initial learning phase are primarily due to inadequate specimens. Interpretation
      of pancreatic EUS-FNA specimens remained consistent before and after training.

PMID- 11979249
TI  - Endoscopic Nd:YAG laser with aggressive multimodality therapy for locally
      advanced esophageal cancer.
AB  - BACKGROUND: Laser therapy of esophageal carcinoma has been limited to management
      of malignant dysphagia. To investigate its cytoreductive potential, Nd:YAG laser
      tumor debulking was added to multimodality therapy. METHODS: From 1994-1998, 29
      patients with advanced locoregional esophageal carcinoma were enrolled in a
      prospective experimental study of high-dose neoadjuvant chemoradiotherapy
      together with endoscopic Nd:YAG laser photoablation. Comparisons were made to a
      retrospective cohort of 31 patients treated from 1990 to 1994 who underwent
      similar neoadjuvant chemoradiotherapy without laser debulking. RESULTS: Laser
      dosage ranged from 3457 to 67,443 J (mean 21,832 [SD 16,999]) delivered in 1 to 6
      (mean 2.6 [1.4]) treatment sessions. Actuarial analysis showed improved survival
      in the laser-treated group versus the reference group (30.1 months vs. 16.5
      months; p = 0.047). Multivariable analysis of the impact of age, T-stage, N
      stage, completion of neoadjuvant therapy, and laser debulking that included all
      patients in both treatment groups showed completion of therapy to be the most
      significant variable associated with survival. There were 3 complications related
      to laser therapy. Relief of dysphagia was achieved in 19 of 29 patients (66%) in
      the laser group versus 13 of 31 (42%) in the reference group. CONCLUSIONS:
      Malignant dysphagia may be more effectively treated by the addition of Nd:YAG
      laser therapy to aggressive multimodality therapy. Improved survival with the
      addition of laser debulking warrants longer follow-up and a prospective
      comparative trial.

PMID- 11979250
TI  - Long-term outcome in patients with benign biliary strictures treated
      endoscopically with multiple stents.
AB  - BACKGROUND: The long-term efficacy of sequential insertion of multiple plastic
      stents for benign biliary strictures is poorly defined. The aims of this study
      were to evaluate the long-term outcome (bile duct patency, complications) of this
      therapy and to identify predictors of a good outcome. METHODS: Retrospective
      review of 29 cases of benign biliary strictures treated with sequential plastic
      stent insertion in progressively increasing numbers and/or of increasing
      diameter. RESULTS: Stricture etiology was as follows: postoperative 19 (66%),
      chronic pancreatitis 9 (31%), and idiopathic 1 (3%). Therapy succeeded in 18
      patients (62%) (mean follow-up 48.0 [11.56] months after stent removal). Therapy
      failed in 11 patients (38%) (mean interval to failure 11.59 [9.79] months after
      stent removal). The 2 groups of patients in which therapy failed had either a
      hilar stricture (n = 4, 25% success) or distal common bile duct stricture caused
      by chronic pancreatitis (n = 9, 44% success). In the remaining cases, therapy
      succeeded in 13 of 16 (81% success). The observed differences in success rate
      among subgroups were not statistically significant. There were no ERCP-related
      deaths. One episode of mild pancreatitis and 2 episodes of cholangitis developed
      during 126 ERCPs over a period of stent insertion of 36 patient years.
      CONCLUSIONS: In selected patients with benign biliary strictures, sequential
      endoscopic insertion of multiple biliary stents may lead to long-term success
      that could be equal to or superior to surgery with minimal morbidity. Hilar
      strictures and those caused by chronic pancreatitis appear to respond poorly to
      this therapy.

PMID- 11979251
TI  - High-resolution chromoendoscopy for classifying colonic polyps: a multicenter
      study.
AB  - BACKGROUND: Chromoendoscopy may reliably separate adenomatous from nonadenomatous
      polyps. The aim of this multicenter trial was to determine the accuracy of high
      resolution chromoendoscopy for the determination of colonic polyp histology.
      METHODS: This multicenter trial included 4 academic centers and a primary care
      practice. In 299 patients referred for routine colonoscopy or sigmoidoscopy, 520
      polyps 10 mm in size were sprayed with indigo carmine dye. Using a high
      resolution endoscope, the endoscopist predicted the histology of each polyp based
      on its surface characteristics. Hyperplastic polyps had a "pitted" surface
      pattern of orderly arranged "dots" that resembled surrounding normal mucosa.
      Adenomatous polyps had at least one surface "groove" or "sulcus." Each polyp was
      subsequently resected for histopathologic evaluation. RESULTS: The resected
      polyps were comprised by 193 adenomas (37%), 225 hyperplastic polyps (43%), and
      102 "other" types (20%). Forty polyps (7.7%) could not be classified by high
      resolution chromoendoscopy with indigo carmine dye. For the remaining polyps, the
      sensitivity, specificity, and negative predictive value of indigo carmine dye
      staining for adenomatous polyps were, respectively, 82%, 82%, and 88%. The
      results were consistent among the academic centers and the primary care practice.
      CONCLUSIONS: High-resolution chromoendoscopy with indigo carmine dye demonstrates
      morphologic detail of diminutive colorectal polyps that can reliably be used to
      separate adenomatous from nonadenomatous polyps.

PMID- 11979252
TI  - Pressure dye-spray: a simple and reliable method for differentiating adenomas
      from hyperplastic polyps in the colon.
AB  - BACKGROUND: Based on 10 years of experience with chromoendoscopy, our hypothesis
      was that colonic adenomas can be differentiated from hyperplastic polyps by use
      of a high-pressure spray-jet of dye (pressure dye-spray). To test the accuracy of
      pressure dye-spray, classification of colonic polyps as adenomas and hyperplastic
      polyps by pressure dye-spray and ordinary colonoscopic findings (shape, size, and
      color surface appearance) were compared. METHODS: Pressure dye-spray
      chromoendoscopy was performed by using 0.035% indigo carmine, a spray-type
      cannula, and a water pump. Polyps were first classified as adenomas or
      hyperplastic polyps by ordinary colonoscopic findings. One or more pressure dye
      spray bursts were then focused on the polyp from a distance of 1 to 2 cm. Polyps
      were classified as adenomas only if oozing of blood was evident; otherwise, they
      were classified as hyperplastic polyps. A histologic diagnosis was obtained for
      all polyps, and the results of ordinary colonoscopic findings and pressure dye
      spray were compared. RESULTS: This study examined 1468 polyps (1201 adenomas, 267
      hyperplastic polyps; mean diameter 4 mm). The sensitivities for polyp
      differentiation with pressure dye-spray and ordinary colonoscopic findings were,
      respectively, 97.9% and 73.4% (p < 0.0001); specificities were, respectively,
      96.6% and 92.1% (p = 0.077). CONCLUSIONS: Pressure dye-spray was found to be a
      reliable technique for differentiation between adenomas and hyperplastic polyps.

PMID- 11979253
TI  - Intraductal papillary mucinous tumor of the pancreas.

PMID- 11979254
TI  - Cecal intussusception.

PMID- 11979255
TI  - Acute graft-versus-host disease in the small intestine.

PMID- 11979256
TI  - Metastatic carcinoma simulating stromal tumor.

PMID- 11979257
TI  - Multiple colonic granular cell tumors.

PMID- 11979258
TI  - Biliary sphincter scissor for pre-cut access: preliminary experience.
AB  - BACKGROUND: Needle-knife papillotomy is often used when selective biliary access
      cannot be achieved. It is difficult to perform and is associated with an
      increased risk of complications. Initial experience with a new device for pre-cut
      access is presented. This device may be easier to use and its use may be
      associated with a lesser risk for complications compared with other methods.
      METHODS: The device is a miniature scissor mounted on a flexible shaft. It is
      used to cut the common channel and a short segment of the intrasphincteric common
      bile duct. The device was used if at least 4 attempts to cannulate the common
      duct with standard methods were unsuccessful in patients requiring biliary
      decompression. Data on outcomes and complications were collected. RESULTS: In 8
      of 12 patients, scissor pre-cut clearly facilitated common bile duct cannulation.
      No complications were encountered. CONCLUSIONS: In this small case series,
      scissor pre-cut papillotomy was safe and effective. Common bile duct access was
      facilitated in the majority of patients studied.

PMID- 11979259
TI  - A novel 3-dimensional EUS technique for real-time visualization of the volume
      data reconstruction process.
AB  - BACKGROUND: Three-dimensional EUS (3D-EUS) technology has facilitated spatial
      interpretation of US images. However, acquisition of consecutive US scans is time
      consuming and difficult. A new 3D-EUS system was developed that negates this
      problem by allowing rapid image renewal and the efficient production of
      consecutive US scans. METHODS: Three-dimensional images were reconstructed from a
      series of 2-dimensional images corresponding to the rotation angle of the
      echoendoscope as measured with an electromagnetic tracking system. To evaluate
      the technical feasibility of the system, 3-dimensional images of splenic veins in
      2 patients and an esophageal submucosal tumor in a third patient were generated.
      RESULTS: The 3D-EUS system acquired image data at a rate of 30 frames per second
      and allowed visualization of these data in real-time. The area of interest was
      clearly and rapidly portrayed in all 3 patients. CONCLUSION: This study
      demonstrates the efficiency of the new 3D-EUS system described in this report.
      Further development of this novel 3D-EUS system may lead to new applications of
      this technology.

PMID- 11979260
TI  - EUS guidance in gastric pacemaker implantation.
AB  - BACKGROUND: EUS provides excellent imaging of the gastric wall. The utility of
      EUS imaging in guiding the placement of a gastric pacemaker was investigated.
      METHODS: Fourteen patients underwent gastric pacemaker implantation for
      refractory gastroparesis at laparotomy. Placement of the lead into the muscle
      layer of the antrum of the stomach was imaged by intraoperative surface
      ultrasonography in the first 8 patients and by EUS in the subsequent 6 patients.
      RESULTS: Surface US examination of the lead placement revealed reverberation
      artifacts. The images were uniformly unsatisfactory and the position of the lead
      in the gastric wall could not be visualized in any patient. In contrast, the lead
      was clearly and easily identified by EUS as a bright linear echo in the gastric
      wall. This was observed uniformly in all of the patients evaluated by EUS.
      Compared with surface US, EUS provided better images of the gastric lead
      placement as well as less abdominal distension and thus easier closure of the
      incision. CONCLUSIONS: EUS is useful in confirming the accurate placement of
      pacemaker leads within the muscular coat of the stomach.

PMID- 11979261
TI  - Biliary drainage by endoscopic choledochoduodenal fistulotomy in patients with
      papillary carcinoma.
AB  - BACKGROUND: There are few reports of endoscopic choledochoduodenal fistulotomy
      (endoscopic fistulotomy) in patients with papillary carcinoma by using a needle
      knife. METHODS: Among 35 patients with papillary carcinoma requiring biliary
      drainage, 14 with a suprapapillary bulge underwent endoscopic fistulotomy alone
      or with widening of the fistula by using a standard sphincterotome or dilation
      balloon catheter. OBSERVATIONS: Transfistula bile duct cannulation was successful
      on the first attempt in 13 of 14 patients (93%) and temporary biliary drainage
      through the fistula was successfully established in all 13 patients. The single
      complication was minor bleeding (7%) in 1 patient. In 6 patients with biliary
      obstruction who were not operative candidates, endoscopic fistulotomy was used
      for palliation, and all remained asymptomatic for a mean period of 3.2 months.
      CONCLUSIONS: Endoscopic fistulotomy is an effective, relatively safe biliary
      drainage procedure. It should be considered in selected patients with bile duct
      obstruction caused by papillary carcinoma and a suprapapillary bulge caused by
      the dilated bile duct.

PMID- 11979262
TI  - A novel method to control severe upper GI bleeding from metastatic cancer with a
      hemostatic sealant: the CoStasis surgical hemostat.

PMID- 11979263
TI  - A new application for therapeutic EUS: main pancreatic duct drainage with a
      "pancreatic rendezvous technique".

PMID- 11979264
TI  - Colonic aphthoid erosions as the only manifestation of tuberculosis: case report.

PMID- 11979265
TI  - Colonoscopic diagnosis of unsuspected diverticulosis.

PMID- 11979266
TI  - Angiolipoma of the colon diagnosed after endoscopic resection.

PMID- 11979267
TI  - A novel duodenal elevated lesion mimicking an intraluminal protrusion.

PMID- 11979268
TI  - Primary duodenal and jejunal tuberculosis: report of two cases.

PMID- 11979269
TI  - Prospects for the worldwide control of colorectal cancer through screening.

PMID- 11979270
TI  - Chromoscopy and zoom colonoscopy.

PMID- 11979271
TI  - African Institute of Digestive Diseases.

PMID- 11979272
TI  - Bile collected from the bile duct without cholecystokinin stimulation may be
      inadequate for the detection of microcrystals.

PMID- 11979273
TI  - Untreatable chest pain after esophageal insertion of self-expanding metal stents.

PMID- 11979274
TI  - Urgent endoscopic sphincterotomy for acute gallstone pancreatitis.

PMID- 11979275
TI  - False negative ERCP in biliary leak.

PMID- 11979276
TI  - Meta-analysis, Part II.

PMID- 11979277
TI  - TREX is a conserved complex coupling transcription with messenger RNA export.
AB  - The essential yeast proteins Yra1 and Sub2 are messenger RNA export factors that
      have conserved counterparts in metazoans, designated Aly and UAP56, respectively.
      These factors couple the machineries that function in splicing and export of
      mRNA. Here we show that both Yra1 and Sub2 are stoichiometrically associated with
      the heterotetrameric THO complex, which functions in transcription in yeast. We
      also show that Sub2 and Yra1 interact genetically with all four components of the
      THO complex (Tho2, Hpr1, Mft1 and Thp2). Moreover, these components operate in
      the export of bulk poly(A)(+) RNA as well as of mRNA derived from intronless
      genes. Both Aly and UAP56 associate with human counterparts of the THO complex.
      Together, these data define a conserved complex, designated the TREX
      ('transcription/export') complex. The TREX complex is specifically recruited to
      activated genes during transcription and travels the entire length of the gene
      with RNA polymerase II. Our data indicate that the TREX complex has a conserved
      role in coupling transcription to mRNA export.

PMID- 11979278
TI  - Understanding protein hydrogen bond formation with kinetic H/D amide isotope
      effects.
AB  - Through the development of a procedure to measure when hydrogen bonds form under
      two-state folding conditions, alpha-helices have been determined to form
      proportionally to denaturant-sensitive surface area buried in the transition
      state. Previous experiments assessing H/D isotope effects are applied to various
      model proteins, including lambda and Arc repressor variants, a coiled coil
      domain, cytochrome c, colicin immunity protein 7, proteins L and G,
      acylphosphatase, chymotrypsin inhibitor II and a Src SH3 domain. The change in
      free energy accompanied by backbone deuteration is highly correlated to secondary
      structure composition when hydrogen bonds are divided into two classes. The
      number of helical hydrogen bonds correlates with an average equilibrium isotope
      effect of 8.6 +/- 0.9 cal x mol(-1) x site(-1). However, beta-sheet and long
      range hydrogen bonds have little isotope effect. The kinetic isotope effects
      support our hypothesis that, for helical proteins, hydrophobic association cannot
      be separated from helix formation in the transition state. Therefore, folding
      models that describe an incremental build-up of structure in which hydrophobic
      burial and hydrogen bond formation occur commensurately are more consistent with
      the data than are models that posit the extensive formation of one quantity
      before the other.

PMID- 11979279
TI  - Designing a 20-residue protein.
AB  - Truncation and mutation of a poorly folded 39-residue peptide has produced 20
      residue constructs that are >95% folded in water at physiological pH. These
      constructs optimize a novel fold, designated as the 'Trp-cage' motif, and are
      significantly more stable than any other miniprotein reported to date. Folding is
      cooperative and hydrophobically driven by the encapsulation of a Trp side chain
      in a sheath of Pro rings. As the smallest protein-like construct, Trp-cage
      miniproteins should provide a testing ground for both experimental studies and
      computational simulations of protein folding and unfolding pathways. Pro Trp
      interactions may be a particularly effective strategy for the a priori design of
      self-folding peptides.

PMID- 11979280
TI  - What's a girl to do?

PMID- 11979281
TI  - Year 2000 Oncology Nursing Society Research Priorities Survey.
AB  - PURPOSE/OBJECTIVES: To determine the Oncology Nursing Society's (ONS's) research
      priorities for 2001-2005 for oncology nursing across the entire scope of cancer
      care, including prevention, detection, treatment, and palliative care. DESIGN: A
      cross-sectional, mailed survey. SAMPLE: Stratified by the general member group
      (i.e., a random sample of 1,850 ONS members) and researcher group (i.e., census
      of 150 ONS researchers). 788 responded for an overall response rate of 39%. MAIN
      RESARCH VARIABLES: 113 topics that were identified from the 1994 ONS Research
      Priority Survey questionnaire and earlier ONS Research Priority Surveys, with the
      addition of 20 new items to existing questionnaire categories and one new
      category area: health services research. FINDINGS: Top 20 research priorities
      were distributed across six of eight questionnaire categories, and the number of
      top 20 priorities within categories differs. Compared to the 1994 survey, 9
      topics were common to both top 20 lists; 8 were new to the top 20, and 11 dropped
      out of the top 20. When the researcher group and adjusted total sample group top
      20 priority ratings were compared, nine topics were common to both groups.
      CONCLUSIONS: Examining research priorities affords different perspectives to
      guide practice, education, research, management, and administration. IMPLICATIONS
      FOR NURSING: ONS Research Priority Survey results provide an important foundation
      for developing future research across the entire scope of oncology nursing.

PMID- 11979282
TI  - Prognostication in advance cancer: nurses' perceptions of the dying process.
AB  - PURPOSE/OBJECTIVES: To determine how experienced nurses describe the dying
      process of patients with advanced cancer. SAMPLE/SETTING: Fifteen nurses,
      experienced in the care of patients with advanced cancer, employed by a midsize
      midwestern hospice or academic inpatient oncology unit. METHODS: Individual
      interviews using structured and semi-structured questions. Responses were content
      analyzed using Krippendorff's techniques. MAIN RESEARCH VARIABLE: Dying process
      in cancer. FINDINGS: Nurses view the dying process as a weeks-to-months-long,
      multidimensional process that encompasses physical, psychosocial, and
      spiritual/existential domains. Impending death is recognized and monitored.
      Common clinical signs include declining interest in life, increased weakness,
      somnolence, and changes in respiratory, circulatory, and cognitive status.
      CONCLUSIONS: Active (or acute) dying processes are recognized and monitored by
      nurses; the complexities and patterns of the phenomenon remain unarticulated.
      IMPLICATIONS FOR NURSING: Future research could explore both empirical and
      contextual aspects of acute dying processes. Nurses are in a position to develop
      useful knowledge about acute dying processes in cancer.

PMID- 11979283
TI  - Direct-to-consumer advertising of prescription medications: implications for
      patients with cancer.
AB  - PURPOSE/OBJECTIVES: To review the phenomenon of direct-to-consumer (DTC)
      advertising of prescription medications in the media, with an overview of
      pertinent studies in the literature regarding patients' and healthcare
      professionals' perspectives on DTC advertising. DATA SOURCES: Journal articles,
      media, and clinical experience. DATA SYNTHESIS: DTC advertising of prescription
      medications is extremely prevalent in U.S. society. Advertising of medications is
      an expensive business; yearly spending is expected to reach $7.5 billion by 2005.
      Although opinions vary regarding DTC advertising, healthcare professionals,
      including oncology nurses, must be prepared to discuss DTC-advertised medications
      and treatments with their patients. CONCLUSIONS: Communication is the key to
      helping patients decipher the deluge of DTC advertisements in the media and
      determine the accuracy of this ever-increasing source of medical information.
      IMPLICATIONS FOR NURSING: Oncology nurses need to be aware of the increases in
      DTC advertising of prescription medications and the importance of guiding
      patients through appropriate medication choices by education.

PMID- 11979284
TI  - A systematic review of the evidence on symptom management of cancer-related
      anorexia and cachexia.
AB  - PURPOSE/OBJECTIVES: To evaluate and synthesize the evidence regarding cancer
      related anorexia and cachexia symptom management and make recommendations for
      future directions. DATA SOURCES: Cochrane Library, MEDLINE, CANCERLIT, CINAHL,
      Dissertation Abstracts, EBM Reviews--Best Evidence, EMBASE, and the Computer
      Retrieval of Information on Scientific Projects. Current overviews, clinical
      trials, systematic research reviews, and meta-analyses. DATA SYNTHESIS: All
      studies focused on increasing food intake. Nonpharmacologic clinical trials
      increased caloric and protein intake but resulted in no improvement in
      nutritional status, weight, tumor response, survival, or quality of life. Weight,
      appetite, and well-being were improved with megestrol acetate, but nutritional
      status was not improved. Some exercise studies demonstrated improvements in
      nutrition-related outcomes, but these were not primary research outcomes.
      CONCLUSIONS: Symptom management of anorexia and cachexia should focus on
      decreasing energy expenditure or minimizing factors creating a negative energy
      balance, as well as improving food intake. Increased measurement sensitivity also
      is needed. IMPLICATIONS FOR NURSING: Improved nutritional assessment skills are
      needed with an emphasis on anticipated problems and current status.

PMID- 11979285
TI  - Fatigue in patients with cancer.
AB  - PURPOSE/OBJECTIVES: To provide a historic perspective on knowledge about fatigue
      in patients with cancer, review what is known, define gaps, and recommend future
      approaches. DATA SOURCES: Published research reports, clinical papers, review
      articles, and practice guidelines. DATA SYNTHESIS: Two tested interventions show
      consistent positive effects: treatment of chemotherapy-induced anemia and aerobic
      exercise. Other frequently suggested interventions, such as adequate nutrition,
      energy conservation, psychostimulants, antidepressants, and increased sleep and
      rest, either have not been tested or studies underway are not yet complete.
      Current practice guidelines are based on a combination of research and expert
      clinical judgment. CONCLUSIONS: The knowledge base on fatigue continues to
      expand. Information about the mechanisms underlying fatigue is needed to develop
      innovative approaches to prevent and treat fatigue. IMPLICATIONS FOR NURSING:
      Current practice guidelines should be used to guide care with the expectation
      that guidelines will evolve to incorporate the results of studies currently
      underway. Although specific gaps in knowledge need to be addressed to guide
      future practice, clinicians need to use existing knowledge in the care they are
      delivering today. All of the interventions proposed for managing cancer treatment
      related fatigue are health policy challenges because they represent additions to
      usual care rather than replacements of existing components of care.

PMID- 11979286
TI  - Quality of life after postmastectomy breast reconstruction.
AB  - PURPOSE/OBJECTIVES: To explore women's expectations about postmastectomy
      reconstruction and factors affecting their quality of life after reconstruction.
      DESIGN: Qualitative focus group study. SETTING: Integrated healthcare system in a
      midwestern suburban community. SAMPLE: 17 women who had undergone mastectomies
      with immediate reconstruction between 1.4 and 5 years previously and had
      participated in a study of women newly diagnosed with breast cancer. METHODS: An
      experienced focus group moderator conducted two focus group sessions. Comments
      from the sessions were audiotaped and transcribed verbatim. The sessions involved
      semistructured, open-ended questions about perceptions of preparation,
      experience, and satisfaction regarding postmastectomy reconstruction. Thematic
      content analysis began with open coding at the level of individual comments and
      proceeded through two levels of higher-order categorization. FINDINGS: Although
      women felt well informed about breast surgery, they wished they had been more
      informed about some issues. Ratings of satisfaction generally were high despite
      some concerns about cosmetic outcome and persistent anxiety about recurrence.
      CONCLUSIONS: Reconstruction allows women to feel comfortable in clothing, but
      recovery can be difficult, and reconstruction does not neutralize the biggest
      emotional challenge of breast cancer: fear of recurrence. IMPLICATIONS FOR
      PRACTICE: Women appreciate thorough information to prepare them for
      reconstruction and recovery. For aspects of recovery in which substantial
      variation exists, the range of experiences should be provided.

PMID- 11979287
TI  - Understanding hope and factors that enhance hope in women with breast cancer.
AB  - PURPOSE/OBJECTIVES: To examine the extent to which antecedent variables and
      appraisals differentiate levels of hope in women during treatment for breast
      cancer. DESIGN: Descriptive, correlational. SETTING: Two large midwestern urban
      areas. SAMPLE: 73 Caucasian women between the ages of 20-73 with first-time
      diagnosis of breast cancer; recruited through five physician offices; within
      three months after surgical intervention with planned chemotherapy, radiation
      therapy, or tamoxifen; and able to read English. METHODS: Identical surveys
      mailed to participants 3 and 12 months after surgery. Instruments included
      Lazarus' Appraisal Components and Themes Scales, Herth Hope Index, Rosenberg's
      Self-Esteem Scale, Personal Resource Questionnaire 85-Part 2, Helpfulness of
      Religious Beliefs Scale, and demographics questionnaire. MAIN RESEARCH VARIABLES:
      Appraisal, hope, self-esteem, social support, and helpfulness of religious
      beliefs. FINDINGS: Variables influencing appraisals during breast cancer
      treatment on both surveys were self-esteem and helpfulness of religious beliefs.
      Potential for coping appraisals and self-esteem contributed to variation in hope
      at both time points. Social support was a significant contributor to hope in the
      12-month survey. Appraisal themes reflected challenge but not fear. CONCLUSIONS:
      Self-esteem and helpfulness of religious beliefs influence women's appraisals
      regarding the potential for coping; appraisals and antecedent variables relevant
      for differentiating hope are beliefs about the potential for coping, self-esteem,
      and social support. IMPLICATIONS FOR NURSING: Care of women with breast cancer
      during the first year of treatment should include assessment of beliefs regarding
      the potential for coping. Results suggest that support for interventions related
      to self-esteem, social support, and helpfulness of religious beliefs increase
      confidence in coping abilities and hope.

PMID- 11979288
TI  - Creating a CD-ROM program for cancer-related patient education.
AB  - PURPOSE/OBJECTIVES: To describe the process of developing a cancer-related
      patient and family education CD-ROM program and initial evaluation results. DATA
      SOURCES: Published research, theory, practice, and personal experience. DATA
      SYNTHESIS: CD-ROM programs can be far more comprehensive than the booklets and
      videotapes used more commonly in patient education. Developing CD-ROM programs
      requires funding, organizational skills, access to content experts, and a team
      composed of people who have the varied skills required for a finished multimedia
      product. The time frame for CD-ROM production is often longer than that of other
      patient-education formats. Published reports and this institution's experience
      confirm that patients accept this medium. Evaluation to date suggests that CD
      ROMs may be more useful to patients and their families than any other single
      information source. CONCLUSIONS: CD-ROM technology is more expensive than
      videotapes and booklets, but it allows for greater depth of content and may
      satisfy a broader range of educational needs than other media. Funding often can
      be obtained through foundations and with unrestricted educational grants from
      pharmaceutical companies. IMPLICATIONS FOR NURSING: Nurses can lead
      multidisciplinary teams to produce CD-ROMs for their patient populations. These
      programs can be used before a patient has a first consultation to introduce a
      cancer or treatment and anytime during cancer diagnosis and treatment. They can
      reinforce one-on-one teaching or provide greater depth of content than ever could
      be provided in individualized teaching sessions. They can facilitate patients'
      self-directed learning and may allow nurses and doctors to teach on a different
      level. These programs also can complement patients' Internet searches either by
      creating a solid foundation for further investigation or by confirming the
      reliability of information gained through a variety of Internet sources.

PMID- 11979289
TI  - Challenges of identifying asian women for breast cancer screening.
AB  - PURPOSE/OBJECTIVES: To emphasize the need for multiple data sources to develop a
      comprehensive list of potential respondents for a study of breast cancer
      screening behavior among Asian American women. DESIGN: Descriptive, pilot.
      SETTING: An urban Michigan county. SAMPLE: 616 Chinese women age 40 and older.
      METHODS: Comparison of multiple data sources, including lists from membership
      directories of local Chinese organizations, a commercial survey company, health
      promotion events, and brief telephone interviews. FINDINGS: Of the 616 eligible
      women, 32% were identified through the membership directories of local Chinese
      organizations, 28% from a list obtained from the survey company, 22% from
      telephone directories, 10% from the attendance lists of health promotion events,
      and 8% from more than one source. CONCLUSIONS: Multiple sources are required to
      obtain a comprehensive list for specialized populations. Every data source has
      its advantages and disadvantages. The use of diverse sources helps to offset the
      limitations of each individual one. IMPLICATIONS FOR NURSING: Identifying
      potential participants from specialized populations represents a major issue for
      clinicians and researchers in nursing and other health-related disciplines.
      Strategies exist to facilitate the process.

PMID- 11979290
TI  - Hot flashes and related outcomes in breast cancer survivors and matched
      comparison women.
AB  - PURPOSE/OBJECTIVES: To compare the hot flash symptom experience and related
      outcomes between breast cancer survivors and healthy women. DESIGN: Descriptive,
      cross-sectional, comparative study. SETTING: Southeastern university medical
      center. SAMPLE: 69 of 207 breast cancer survivors contacted via a tumor registry
      and 63 age-matched healthy female volunteers. Survivors were a mean of 57 years
      and a mean of 39 months postdiagnosis. METHODS: Mailed survey included a
      demographic, disease, and treatment information form; a gynecologic history form;
      a two-day, prospective, hot flash diary; a detailed hot flash questionnaire; mood
      and affect scales; and the Hot Flash-Related Daily Interference Scale. MAIN
      RESEARCH VARIABLES: Hot flashes, mood, affect, interference with daily
      activities, and overall quality of life. FINDINGS: Breast cancer survivors had
      hot flashes that were significantly more frequent, severe, distressing, and of
      greater duration. Breast cancer survivors were less likely to be using hormone
      replacement and more likely to have tried nonhormonal prescription interventions
      in the past, but reported significantly less effectiveness from hot flash
      treatments. Breast cancer survivors with severe hot flashes reported
      significantly greater mood disturbance; higher negative affect; more interference
      with daily activities, including sleep, concentration, and sexuality; and poorer
      overall quality of life in comparison to breast cancer survivors with no hot
      flashes to mild hot flashes. Hot flash quality and triggers were not
      significantly different between groups. No clear temporal pattern of hot flashes
      emerged. CONCLUSIONS: Hot flashes are a significant problem for breast cancer
      survivors, even for those who are naturally postmenopausal (i.e., did not undergo
      menopause as a result of surgery or the effects of chemotherapy). Hot flashes
      remained fairly stable over time and did not diminish in frequency, severity, or
      associated distress. IMPLICATIONS FOR NURSING: The findings guide the assessment
      of the uniqueness of the problem of hot flashes experienced by breast cancer
      survivors and help define outcomes to address in clinical practice or include in
      future hot flash intervention research.

PMID- 11979291
TI  - Comparing the results of coagulation tests on blood drawn by venipuncture and
      through heparinized tunneled venous access devices in pediatric patients with
      cancer.
AB  - PURPOSE/OBJECTIVES: To compare the accuracy of three coagulation tests
      (prothrombin time [PT], activated partial thromboplastin time [aPTT], and
      fibrinogen [FBG]) performed on blood samples collected through heparinized
      tunneled venous access devices (TVADs) with those from venipuncture. DESIGN:
      Descriptive comparative with patients serving as their own controls. SETTING:
      Pediatric comprehensive care setting for children and adolescents experiencing
      catastrophic diseases. SAMPLE: 53 patients who had TVADs, had not received
      asparaginase during the previous 14 days, and had coagulation studies ordered.
      Patients ranged in age from 2-20 years (mean = 9.2 years, SD = 5). The most
      common diagnoses were neuroblastoma and acute myelocytic leukemia. METHODS: Blood
      was collected through TVADs within seconds of collection of the venipuncture
      sample. The first 3 ml of blood from a TVAD was discarded; the research nurse
      then drew three sequential samples of 3 ml each. Laboratory personnel were
      blinded to the source of all four samples until all analyses had been completed.
      MAIN RESEARCH VARIABLES: PT, aPTT, and FBG. FINDINGS: For all patients, results
      of PT, aPTT, and FBG tests on each of the three blood samples obtained through
      the TVAD differed significantly from results of the same tests on blood obtained
      by venipuncture. CONCLUSIONS: These findings indicate that neither a 6 ml, 9 ml,
      nor 12 ml discard from a heparinized TVAD is sufficient to yield clinically
      trustworthy PT, aPTT, or FBG values. IMPLICATIONS FOR NURSING: Nurses who have
      been persuaded by patients or parents to withdraw blood samples for coagulation
      indicators from a TVAD rather than from a venipuncture should have access to this
      research-based information that the three indicators, particularly aPTT, differ
      significantly from each other as to make it unreliable and potentially unsafe to
      sample blood from a TVAD to assess coagulation.

PMID- 11979292
TI  - Therapeutic effects of massage therapy and handling touch on caregivers of
      patients undergoing autologous hematopoietic stem cell transplant.
AB  - PURPOSE/OBJECTIVES: To examine the effect of massage therapy and Healing Touch on
      anxiety, depression, subjective caregiver burden, and fatigue experienced by
      caregivers of patients undergoing autologous hematopoietic stem cell transplant.
      DESIGN: Quasi-experimental repeated measures. SETTING: Oncology/hematology
      outpatient clinic in a large midwestern city. SAMPLE: 36 caregivers: 13 in the
      control group, 13 in the massage therapy group, and 10 in the Healing Touch
      group. Average age was 51.5 years; most participants were Caucasian. METHODS: All
      caregivers completed the Beck Anxiety Inventory, the Center for Epidemiologic
      Studies Depression Scale, the Subjective Burden Scale, and the Multidimensional
      Fatigue Inventory-20 before and after treatment consisting of two 30-minute
      massages or Healing Touch treatments per week for three weeks. Caregivers in the
      control group received usual nursing care and a 10-minute supportive visit from
      one of the researchers. MAIN RESEARCH VARIABLES: Anxiety, depression, subjective
      burden, fatigue, Healing Touch, massage therapy. FINDINGS: Results showed
      significant declines in anxiety scores, depression, general fatigue, reduced
      motivation fatigue, and emotional fatigue for individuals in the massage therapy
      group only. In the Healing Touch group, anxiety and depression scores decreased,
      and fatigue and subjective burden increased, but these changes did not achieve
      statistical significance. CONCLUSIONS: Caregivers can benefit from massage
      therapy in the clinic setting. IMPLICATIONS FOR NURSING: Oncology nurses care for
      both patients and their caregivers. Although some transplant programs provide
      services to support lay caregivers, studies indicate that these individuals
      continue to feel stressed by their situation. Massage might be one intervention
      that can be used by nurses to decrease feelings of stress in patients'
      caregivers.

PMID- 11979301
TI  - Second hematopoietic stem cell transplantation for the treatment of graft
      failure, graft rejection or relapse after allogeneic transplantation.
AB  - Failure to engraft after hematopoietic stem cell transplantation (graft
      dysfunction) or to sustain engraftment (graft rejection) is a formidable
      complication due to many possible factors. These include inadequate stem cell
      numbers, infections, graft-versus-host disease and immunological mediated
      processes. Fortunately, this complication is uncommon and can be overcome by
      additional hematopoietic stem cell infusions. Multiple treatment alternatives
      have been explored including hematopoietic growth factors, additional infusions
      of stem cells alone, with augmented immunosuppression or with additional
      cytotoxic therapy. Various sources of the additional stem cells are feasible
      including the original donor, using another donor, using stem cells collected
      from the marrow or after cytokine mobilization from the peripheral blood. This
      report will overview this complication and review the various studies that have
      attempted to define both cause and therapy. However, a lack of well-designed
      prospective studies has made definitive recommendations difficult although basic
      principles have been established.

PMID- 11979302
TI  - Antibody and pre- plus post-transplant prednisone treatments support T cell
      depleted stem cell engraftment without drug-induced morbidity.
AB  - Rigorous T cell depletion methods can now be used to reduce the risk of graft
      versus-host disease (GVHD) associated with allogeneic, hematopoietic stem cell
      transplantation (HSCT). However, full T cell depletion is also associated with a
      significant risk of graft failure. Here we hypothesize that engraftment failures
      after T cell-depleted HSCT may be due, in part, to the absence of GVHD
      prophylaxis. To test this hypothesis, we used a haploidentical mouse model to
      systematically measure the effects of immunosuppressive drug treatments and anti
      T cell antibodies on engraftment. Results showed that engraftment was supported
      in all animals when hosts were pre-treated with anti-T cell antibodies, but donor
      chimerism was significantly improved when hosts were also treated with
      prednisone. Interestingly, when hosts received only pre-HSCT prednisone
      treatments, engraftment was not improved; when hosts received only post-HSCT
      prednisone (initiated near the time of irradiation), the animals became extremely
      ill. Results therefore demonstrated the need for both pre- and post-HSCT
      prednisone treatments as a means to ensure engraftment without morbidity in all
      host animals.

PMID- 11979303
TI  - Persistent decrease in proliferative potential of marrow CD34(+)cells exposed to
      early-acting growth factors after autologous bone marrow transplantation.
AB  - Post-graft hematopoiesis is characterized by long-term quantitative deficiency in
      marrow progenitor cells in both autologous and allogenic settings. In order to
      evaluate the function of post-graft progenitor cells, the proliferative capacity
      of marrow CD34(+) cells was evaluated in 10 patients 6 months after autologous
      bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma and compared to
      that of 10 patients before ABMT and 10 normal controls. Immuno-selected CD34(+)
      cells were cultured for 7 days in liquid serum-free medium with a combination of
      early-acting GF consisting of stem cell factor, IL-3 and IL-1beta. Clonogenic
      efficiency of unselected cells for CFU-GM and BFU-E was decreased in post-graft
      patients compared to pre-graft and control patients. However, clonogenic
      efficiency of selected CD34(+) cells for CFU-GM was not different in post-graft,
      pre-graft and control patients but BFU-E values of post-graft patients remained
      lower than those of control patients. Decreased percentages of CD34(+) CD38(-)
      cells were observed in both post-graft and pre-graft patients while those of
      CD34(+) c-kit(+) cells were similar in all three patient groups. After 7-day
      liquid culture, expansion yields of total progenitor cells were significantly
      lower in post-graft patients (147 +/- 28%) than in pre-graft (255 +/- 27%) and
      control patients (246 +/- 23%). Post-graft deficiency in progenitor cell
      expansion was particularly marked for BFU-E (61 +/- 24%) compared to pre-graft
      patients (220 +/- 82%) and to controls (349 +/- 82%). These results indicate
      impaired proliferative potential of marrow CD34(+) cells several months after
      ABMT involving erythroid progenitor cells and/or commitment towards erythroid
      lineage from a more immature stage (pre-CFU).

PMID- 11979304
TI  - Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic
      stem cells.
AB  - One hundred and seventy-seven stem cell apheresis procedures performed on 91
      patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed
      on 37 patients using the Cobe Spectra cell separator were studied to compare the
      CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+)
      cell content in the blood volumes processed that is harvested) of the two
      machines. The absolute peripheral blood CD34(+) cell count was comparable for the
      two groups (P = 0.27). A strong correlation was seen between the blood CD34(+)
      cell count and the total number of CD34(+) cells collected for the Spectra (r(2)
      = 0.59; P < 10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P < 10(-6)). No
      significant correlation emerged between the peripheral blood CD34(+) cell count
      and the CE of either machine. The total number of CD34(+) cells collected per
      procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and
      median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra
      (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7
      89.3%; P < 0.00001). We conclude that the CD34(+) cell CE of the Spectra is
      superior to that of the CS 3000 Plus. Therefore, under the usual clinical
      conditions, Cobe Spectra should be used preferentially for peripheral blood
      progentor cell collection to maximize the number of hematopoietic stem cells
      collected.

PMID- 11979305
TI  - Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow
      transplantation.
AB  - Effects of polymorphisms in TNFA and TNFR2 on the outcome of 462 cases of
      unrelated bone marrow transplantation (uBMT) were studied retrospectively. Four
      alleles of TNFA (U01-U04) distinguished by polymorphism in the upstream region, 
      1031 (T/C), -863 (C/A) and -857 (C/T), and two alleles of TNFR2 (196M/196R)
      distinguished by polymorphism at codon 196 were determined. Transplantation
      involving TNFA-U02- and/or U03-positive donors and/or recipients resulted in a
      higher incidence of graft-versus-host disease (GVHD) of grade III-IV (P < 0.05
      for donor type, P < 0.01 for recipient type) and a lower relapse rate than that
      involving TNFA-U01 homozygous recipients and/or donors (P < 0.025 for donor type,
      P < 0.01 for recipient type). These results include the HLA mismatching effect
      due to linkage disequilibirium of TNFA with HLA loci. However, the effects were
      also observed in HLA-A, -B and -DRB1 allele-matched transplantation.
      Transplantation from TNFR2-196R-positive donors exhibited a higher incidence of
      severe GVHD (P < 0.05) and tendency for a lower relapse rate than that from TNFR2
      196M homozygous donors. TNFR2-196R of recipient origin had no effect on GVHD but
      increased the relapse rate (P < 0.025). These results suggest that TNFA and TNFR2
      typings are helpful for predicting uBMT outcome and for preventing severe
      complications at an early stage.

PMID- 11979306
TI  - Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to
      autologous PBSCT.
AB  - Several trials have shown the activity of thalidomide (THAL) in relapsed multiple
      myeloma (MM) patients failing PBSCT or conventional chemotherapy. PBSCT is
      considered standard treatment for most patients requiring therapy for MM;
      however, patients with VAD-resistant disease may not be able to receive PBSCT due
      to rapidly advancing disease. We report four cases of VAD-refractory MM salvaged
      with THAL + VAD followed by PBSCT. All patients underwent stem cell mobilization
      with cyclophosphamide (Cy) (4.5 g/m(2)) and GMCSF. Melphalan (140-200 mg/m(2))
      was given as conditioning. All patients engrafted within 12-16 days after PBSCT.
      Day +100 evaluation showed the following: very good partial response (n = 1) and
      complete response (n = 3). After a median follow-up to 153 days, two patients
      continue to take THAL with no signs of disease progression. One patient developed
      CHF and was taken off THAL while another patient has died of progressive disease
      while on THAL (MTD 50 mg). In conclusion, VAD-refractory patients were salvaged
      with the addition of THAL to VAD. They were subsequently able to undergo
      autologous PBSCT for MM, which will likely improve their overall survival. This
      suggests that THAL and other related immunomodulatory drugs may prove useful for
      initial MM therapy in combination with standard chemotherapy followed by PBSCT.

PMID- 11979307
TI  - The role of molecular monitoring in autotransplantation for non-Hodgkin's
      lymphoma.
AB  - Seventy-two patients with non-Hodgkin's lymphoma were evaluated for the presence
      of molecular markers (IgH, bcl-1, bcl-2 rearrangement) on bone marrow, at
      diagnosis and after PBSCT, and on harvests in order to find a possible predictive
      role of minimal residual disease on treatment outcome. At diagnosis, 41 (59%) out
      of 69 available bone marrows showed molecular involvement. Fifty-six percent of
      leukaphereses were involved, mainly indolent lymphoma (P = 0.001) or advanced
      disease (P = 0.01). Ex vivo purging cleared only one stem collection out of 31
      PCR-positive leukaphereses. Aggressive lymphomas showed both a longer overall
      survival (OS) (P = 0.03) and relapse-free survival RFS (P = 0.02) when
      transplanted with unpurged stem cells, whereas indolent NHL survival was not
      influenced by ex vivo purging. Twenty out of 26 samples taken during follow-up
      had bone marrow involvement at diagnosis. Of these, 15 cleared their bone marrow;
      both OS and RFS were significantly longer in the PCR-negative cases (P = 0.05 and
      P = 0.005). At 1 year after PBSCT, 75% of patients were PCR negative, with 50%
      molecular remissions; the relapse rate was 55% for patients still PCR positive vs
      29% for those who were PCR negative. Thus, after high-dose chemotherapy, close
      molecular monitoring of MRD using qualitative PCR techniques seems to represent a
      reliable prognostic indicator.

PMID- 11979308
TI  - Changing pattern of bacterial susceptibility to antibiotics in hematopoietic stem
      cell transplant recipients.
AB  - Adequate infection prophylaxis and empirical antibiotic therapy are of critical
      importance after hematopoietic stem cell transplantation (HSCT). We examined the
      evolution of bacterial susceptibility to antibiotics in 492 patients (198
      allografts and 294 autografts) transplanted between 1982 and 1999 and evaluated
      whether ciprofloxacin prophylaxis and an empirical antibiotic regimen
      (glycopeptide + third-generation cephalosporin) were still valid. We collected
      all susceptibility tests performed during the initial hospitalization on blood
      cultures as well as routine surveillance cultures and analyzed susceptibility to
      ciprofloxacin and to major antibiotics used in our unit. Gram-positive cocci
      rapidly became resistant to ciprofloxacin (susceptibility around 70% in 1990 to
      less than 20% in 1998) but sensitivity to glycopeptides remained unaltered. There
      was a rapid decline in the number of patients colonized with Gram-negative
      bacilli in the early years of ciprofloxacin prophylaxis. However, susceptibility
      to ciprofloxacin fell sharply from around 90% in 1990 to around 30% in 1999. In
      parallel, susceptibility to ceftazidime also decreased to less than 80% in recent
      years. Piperacillin (+/- tazobactam) did not show any variation over time and its
      efficacy remained too low (about 60%). Imipenem as well as recently introduced
      cefepim and meropenem showed stable and excellent profiles (>90% susceptibility).
      IN CONCLUSION: (1) quinolone prophylaxis has now lost most of its value; (2) the
      choice of a third-generation cephalosporin for empirical antibiotic therapy may
      no longer be the best because of the emergence of Gram-negative strains resistant
      to beta-lactamases, such as Enterobacter sp. More appropriate regimens of
      empirical antibiotic therapy in HSCT recipients may be based on the use of a
      carbapenem or fourth-generation cephalosporin.

PMID- 11979309
TI  - Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in
      allogeneic stem cell transplantation.
AB  - Human herpesvirus 6 (HHV-6) infection and disease are serious complications of
      allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV)
      is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has
      not been well characterized in vivo. We retrospectively compared the HHV-6
      reactivation rate in pediatric allo-SCT recipients with and without GCV
      prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients
      without prophylactic GCV administration was significantly higher than that in
      those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients
      without prophylactic GCV showed clinical manifestations including skin rash,
      interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and
      thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed
      in one of the 13 patients receiving prophylactic GCV. This patient showed fever,
      diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA
      copy number. Patients who received GCV for treatment of HHV-6 infection showed an
      improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is
      effective for treating HHV-6 disease after allo-SCT in vivo.

PMID- 11979310
TI  - Monitoring of cytomegalovirus reactivation after allogeneic stem cell
      transplantation: comparison of an antigenemia assay and quantitative real-time
      polymerase chain reaction.
AB  - Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain
      reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic
      stem cell transplantation. The number of CMV antigen-positive cells by the
      antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The
      sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%,
      respectively, using real-time PCR as the reference standard. The probability of
      positive antigenemia at day 100 was 76.5%, with a median of first detection at
      day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33,
      respectively. When HLA-identical sibling donor transplant recipients and other
      donor transplant recipients were analyzed separately, there was no difference
      between the two tests. However, temporal patterns of first detection of CMV
      antigen-positive cells and CMV DNA differed between HLA-identical and alternative
      recipients; patients without CMV (29%) or with sporadic positive PCR results
      (14%) were more common in HLA-identical sibling transplants, whereas patients
      with simultaneous antigenemia and positive PCR occurred more in alternative
      transplants (48%). Two of 51 patients (4%) developed CMV colitis despite
      antigenemia-guided prophylaxis, but both were successfully treated with
      ganciclovir. Although PCR is more sensitive than antigenemia, both tests are
      useful in the early detection of CMV after allogeneic stem cell transplantation.

PMID- 11979311
TI  - Management of erectile dysfunction by combination therapy with testosterone and
      sildenafil in recipients of high-dose therapy for haematological malignancies.
AB  - Erectile dysfunction (ED) is a well recognised complication of bone marrow
      transplantation, which affects quality of life in adult patients. Although the
      major contributory factors include hypogonadism and psychogenic factors, the best
      treatment still remains to be established due to the complex aetiopathology of
      the condition. Here, we report our preliminary results in eight patients treated
      with testosterone replacement therapy and sildenafil. We studied eight male
      recipients of BMT aged 22-58 years, presenting with clinical features of
      hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed
      clinically and by colour flow Doppler studies of the cavernosal vessels.
      Testicular function was assessed by testicular volume, FSH, LH and testosterone
      (T) measurements. Erectile performance, libido and ejaculatory function were
      determined by a structured interview. Patients had severe primary hypogonadism as
      evidenced by low mean testicular volume, elevated gonadotrophins and low normal
      mean testosterone levels compared with controls. All had Leydig cell
      insufficiency (LCI) with or without frank serum testosterone insufficiency. All
      except one had cavernosal arterial insufficiency. All patients received
      intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months
      and 50-100 mg of sildenafil orally, one to two times per week. All patients
      responded favourably as substantiated from the NIH consensus criteria. Our
      preliminary results suggest that this combined therapy is a safe and effective
      therapeutic approach in recipients of high-dose therapy presenting with ED after
      transplant.

PMID- 11979312
TI  - Osteochondroma after pediatric hematopoietic stem cell transplantation: report of
      eight cases.
AB  - Eight children developed osteochondroma (OS) at a mean of 88 months after
      hematopoietic stem cell transplantation (HSCT). The mean age at HSCT was 56
      months (12-84). This represents a cumulative incidence of 20% among patients less
      than 18 years of age transplanted from 1981 to 1997. These eight patients
      underwent allogeneic (n = 2) or autologous (n = 6) transplantation for either
      acute leukemia (n = 6) or neuroblastoma (n = 2) after a conditioning regimen
      including TBI (n = 7) or a combination of Bu and CY. OS was multiple in seven
      patients and solitary in one. Eight lesions were resected and all were benign.
      Four children received growth hormone before diagnosis of OS, but there was no
      clinical, radiological or histological difference between those who did not.
      Univariate analysis showed an increased rate associated only with autologous
      HSCT, with a 31.7% probability of a new OS at 12 years after HSCT. Osteochondroma
      should be added to the other adverse effects of HSCT in children.

PMID- 11979313
TI  - Prophylactic T cell infusion after T cell-depleted bone marrow transplantation in
      patients with refractory lymphoma.
AB  - Fifty-two patients with refractory lymphoma were prospectively treated with
      prophylactic T lymphocyte infusion after T cell-depleted allogeneic bone marrow
      transplantation, to induce graft-versus-lymphoma effect. Thirty-three patients
      had related donors; 19 had unrelated donors. After transplantation with marrow
      that had 0.8 +/- 0.4 x 10(5)CD3(+) cells/kg, T cells up to 1.75 x 10(6) CD3(+)
      cells/kg were given over 3 months provided > or = grade II acute graft-versus
      host disease (GVHD) was not seen. The cumulative incidence of grades II-IV acute
      GVHD was 69%. Twenty of 32 evaluable patients (63%) developed chronic GVHD. Ten
      patients (19%) died of GVHD. The Kaplan-Meier 5-year overall survival of all
      patients was 34%. On multivariate analyses, chronic GVHD was significant for
      relapse (hazard ratio of 1.7, P < 0.05), and for overall survival (hazard ratio
      1.4, P < 0.001). Chemosensitivity was significant for relapse only on univariate
      analysis. Patients who developed chronic GVHD had 4 years median survival,
      compared with 9 months in patients without chronic GVHD, P < 0.001. The study
      shows that patients with chronic GVHD have superior survivals, most probably
      related to a graft-versus-lymphoma effect, which could be modulated by
      prophylactic T cell infusion.

PMID- 11979314
TI  - Stable mixed chimerism after T cell-depleted allogeneic hematopoietic stem cell
      transplantation using conditioning with low-dose total body irradiation and
      fludarabine.
AB  - Although reduced intensity conditioning (RIC) before allografting is associated
      with low treatment-related morbidity and mortality, graft-versus-host disease
      (GVHD) remains a significant complication of hematopoietic stem cell
      transplantation (HSCT). T cell depletion (TCD) has been successfully used in
      conventional allotransplantation to reduce the incidence of GVHD, but was
      associated with an increased rate of engraftment failure. In a small cohort of
      six patients at high risk of developing GVHD we have determined whether sustained
      engraftment could be achieved using reduced intensity conditioning and T cell
      depletion in combination. All patients engrafted and 5/6 developed high levels
      (i.e. > or =95%) of donor chimerism, even though mismatched related or matched
      unrelated donors were used. Only one patient developed acute GVHD, as he received
      donor lymphocyte infusions (DLI) for relapse. In summary, TCD might be a useful
      prophylactic tool in RIC allogeneic HSCT. Although TCD after RIC might be
      associated with high relapse rate, as 5/6 patients are not in remission, this
      combined strategy might be appropriate for patients with less aggressive
      malignant or non-malignant diseases in which high transplant-related morbidity
      and mortality is not acceptable.

PMID- 11979316
TI  - Human parainfluenza type 4 virus (hPIV4) infection provoking many questions
      regarding the role of this virus as the causative agent of respiratory tract
      infections in the post-transplant setting.

PMID- 11979315
TI  - B cell function after haploidentical in utero bone marrow transplantation in a
      patient with severe combined immunodeficiency.
AB  - An in utero paternal CD34(+) cell transplant was performed in a T-B+NK+ SCID
      fetus. We report here the results of the 3-year humoral immune reconstitution
      study. The methods used were ApoB VNTR typing, flow cytometry, nephelometry,
      hemagglutination, ELISA, ELISPOT and lymphoproliferative assays. The T cells were
      of donor origin whereas monocytes, B and NK cells were of host origin. Peripheral
      B cell counts and IgM levels were normal since birth. IVIG therapy was required
      at 5 months of age until 2 years old. IgA levels > or =20 mg/dl were detected
      from month 17 post transplantation. Isohemagglutinins were present since month 8
      post transplantation, the highest titers (anti-A:1/128, anti-B:1/32) were
      obtained at month 33 post-transplantation. After immunization with rHBsAg,
      circulating anti-HBsAg IgG secreting cells and a 7.8-fold increase in serum anti
      HBsAg Ab were detected. We conclude that split chimerism following in utero
      haploidentical BMT allows complete humoral immune reconstitution in a T-B+NK+
      SCID patient.

PMID- 11979317
TI  - Allogeneic BMT for infantile acute leukemia: what is the optimal conditioning
      regimen?

PMID- 11979318
TI  - Clearance of erythrocyte allo-antibodies using Rituximab.

PMID- 11979319
TI  - Erectile dysfunction: prevalence and associated variables in patients with
      chronic renal failure.
AB  - Patients with chronic renal failure (CRF) experience a significant decrease in
      quality of life, due both to the limitations imposed by the disease as well as
      the demands of the treatment that they receive. Some side effects of both illness
      and treatment contribute to increase the morbidity of these patients. Among them,
      erectile dysfunction (ED) is notable. One hundred and nineteen patients received
      clinical and laboratory evaluation. The following clinical data were observed:
      age, education, income, race, period of dialysis, period of complaints of ED,
      etiology of ED, use of erythropoietin, presence of arterial hypertension and/or
      diabetes mellitus, use of antihypertensive drugs, use of cigarettes, and psycho
      emotional state of the patients. Assessment of complaints of ED was achieved
      using the International Index of Erectile Function (IIEF). The following
      laboratory data were analyzed: hemoglobin, hematocrit, free testosterone,
      gonadotrophin levels (FSH and LH), HDL-cholesterol, total cholesterol, prolactin,
      and parathyroid hormone. Statistical analysis of the means of continuous
      variables was performed through use of the Student's t-test. Analysis of
      significance of category variables was performed using the chi(2) test.
      Descriptive analysis was obtained through use of the clinical and socio
      demographic data. A multivariate model was created and the odds ratio calculated.
      The average age of the patients was 47.3+/-15.9 y. The mean duration of erectile
      dysfunction complaints was 4 y. The average duration of dialysis was 66.2+/-58.9
      months. Prevalence of erectile dysfunction in this population was 57.9%. The main
      known etiology of chronic renal failure was glomerulonephritis. The main
      variables associated with erectile dysfunction were age, psycho-emotional state,
      and levels of HDL-cholesterol. This study showed a high prevalence of erectile
      dysfunction in the group of patients examined. Factors such as age, anxiety and
      depressive complaints, and dyslipidemy seem to play an important role in the
      origin of erectile dysfunction in such patients.

PMID- 11979321
TI  - Distal penile prosthesis extrusion: treatment with distal corporoplasty or Gortex
      windsock reinforcement.
AB  - Subcutaneous extrusion of penile prosthesis cylinders beneath the glans penis is
      an unusual but difficult complication of penile prosthesis. Without surgical
      repair, extrusion, infection, and corporeal fibrosis may ensue. Twenty-eight
      patients with distal corporeal extrusion were reviewed to identify the optimum
      treatment outcome for these penile prosthesis complications. Records of 28 men
      with subcutaneous distal penile prosthesis cylinder extrusion were reviewed. Mean
      age was 56.2 y. Etiology of erectile dysfunction was diabetes mellitus in 11,
      vasculogenic in 10, Peyronie's disease in five, radical pelvic surgery in five.
      Duration of penile prosthesis was 8-72 months (mean 42.6). No patient had penile
      prosthesis infection or device exposure through the skin. Distal corporoplasty
      was treated on 18/28 men using cylinder repositioning and direct tunica albuginea
      repair. Ten men underwent repair using a Gortex windsock. 8/18 corporoplasty and
      6/10 windsock patients required glans fixation for treatment of hypermobile glans
      following cylinder relocation. In two patients with windsock repair, extrusion
      recurrence occurred 6 and 18 months following surgery and 1/6 had post operative
      infection requiring prosthesis removal. Mean surgical time for corporoplasty was
      52.8 minutes while windsock reconstruction was 89.6 minutes. Distal subcutaneous
      penile prosthesis cylinder extrusion produces coital pain and predisposes to
      cylinder exposure and infection. Early repair with or without additional
      prosthetic materials will return penile prostheses to a normal functioning state.
      Distal corporoplasty with cylinder repositioning appears to be a simple, low
      morbidity solution to this difficult dilemma. Outcomes with distal corporoplasty
      result in better function, less pain, and fewer recurrences than Gortex windsock
      repair.

PMID- 11979320
TI  - Comparison of effects of angiotensin peptides in the regulation of clitoral
      cavernosum smooth muscle tone.
AB  - The isometric tension measurement and in vitro autoradiography were used in
      clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and
      ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced
      contraction was five times less active than ANG II, whereas ANG IV-induced
      contraction was 1181-fold less potent than ANG II. Contractile responses to ANG
      III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT
      1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist
      PD 123,319. Pre-treatment with Nomega-nitro-L-arginine methyl ester, nitric oxide
      (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG
      IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG
      IV-induced contractions. Specific binding sites for 125I-ANG II were found in the
      clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG
      peptides. This study suggests that the contractile responses to all four peptides
      of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further,
      the rank order of potency of contraction was as follows, ANG II> ANG I>ANG
      III>ANG IV. It is also suggested that peptides of the ANG family have a cross
      talk with the NO system and aminopeptidase is involved in the modulation of the
      tone of clitoral CSM by ANG III and ANG IV.

PMID- 11979322
TI  - Contractile response of horse deep dorsal penile vein to histamine.
AB  - The present investigation was designed to evaluate the effect of histamine on
      isolated rings of horse deep dorsal penile vein. Under precontracted or basal
      conditions, histamine evoked an endothelium-independent contraction.
      Preincubation of the vein rings with the selective H1 receptor antagonist,
      mepyramine, shifted the concentration-response curve for histamine and to the H1
      receptor agonist 2-pyridylethylamine to the right in a competitive manner.
      Pretreatment with cimetidine, a specific H2 receptor antagonist, did not modify
      the pEC50 and maximal contraction of the histamine response. Cimetidine and
      propranolol failed to induce a change in the relaxation caused by dimaprit, the
      H2 receptor agonist. Histamine contraction was unaffected by thioperamide, the
      specific H3 receptor antagonist. (R)-alpha-methylhistamine, the H3 receptor
      agonist, also induced contractions which persisted in the presence of either
      thioperamide or tetrodotoxin. These data indicate that horse deep dorsal penile
      vein shows an endothelium-independent contraction response to histamine, mainly
      mediated by H1 receptors.

PMID- 11979323
TI  - Sexual inactivity results in reversible reduction of LH bioavailability.
AB  - We have recently documented significantly reduced serum testosterone (T) levels
      in patients with erectile dysfunction (ED). To understand the mechanism of this
      hypotestosteronemia, which was independent of the etiology of ED, and its
      reversibility only in patients in whom a variety of nonhormonal therapies
      restored sexual activity, we measured serum luteinizing hormone (LH) in the same
      cohort of ED patients (n=83; 70% organic, 30% nonorganic). Both immunoreactive LH
      (I-LH) and bioactive LH (B-LH) were measured at entry and 3 months after therapy.
      Based on outcome (ie number of successful attempts of intercourse per month),
      patients were categorized as full responders (namely, at least eight attempts;
      n=51), partial responders (at least one attempt; n=20) and non-responders (n=16).
      Compared to 30 healthy men with no ED, baseline B-LH (mean+/-s.d.) in the 83
      patients was decreased (13.6+/-5.5 vs 31.7+/-6.9 IU/L, P<0.001), in the face of a
      slightly increased, but in the normal range, I-LH (5.3+/-1.8 vs 3.4+/-0.9 IU/L,
      P<0.001); consequently, the B/I LH ratio was decreased (3.6+/-3.9 vs 9.7+/-3.3,
      P<0.001). Similar to our previous observation for serum T, the three outcome
      groups did not differ significantly for any of these three parameters at
      baseline. However, outcome groups differed after therapy. Bioactivity of LH
      increased markedly in full responders (pre-therapy=13.7+/-5.3, post
      therapy=22.6+/-5.4, P<0.001), modestly in partial responders (14.8+/-6.9 vs
      17.2+/-7.0, P<0.05) but remained unchanged in non-responders (11.2+/-2.2 vs
      12.2+/-5.1). The corresponding changes went in the opposite direction for I-LH
      (5.2+/-1.7 vs 2.6+/-5.4, P<0.001; 5.4+/-2.2 vs 4.0+/-1.7, P<0.05; 5.6+/-1.2 vs
      5.0+/-1.2, respectively), and in the same direction as B-LH for the B/I ratio
      (3.7+/-4.1 vs 11.8+/-7.8, P<0.001; 4.2+/-4.3 vs 5.8+/-4.2, P<0.05; 2.1+/-0.7 vs
      2.6+/-1.3, respectively). We hypothesize that the hypotestosteronemia of ED
      patients is due to impaired bioactivity of LH. This reduced bioactivity is
      reversible, provided that resumption of sexual activity is achieved regardless of
      the therapeutic modality. Because biopotency of pituitary hormones is controlled
      by the hypothalamus, LH hypoactivity should be due to the hypothalamic functional
      damage associated to the psychological disturbances which unavoidably follow
      sexual inactivity.

PMID- 11979325
TI  - Causes of sexual decline in aging married men: Germany and America.
AB  - Married men in Germany (n=48) and America (n=50) between 50 and 80 years old,
      none in poor health, provided comparable information on sexual behavior and
      attitudes, and gave saliva samples from which testosterone was assayed. Sexuality
      declines with age, as expected. Neither testosterone nor psychological depression
      explain levels of sexuality. In both nations, wife's desire for intercourse,
      subject's ability to maintain an erection, and subject's imagination about other
      women, explain certain aspects of sexuality. Subject's health and marital
      satisfaction are related to sexuality among Americans but not among Germans.
      Behavioral models for the two nations are compared.

PMID- 11979326
TI  - Development of a rat model of sexual performance anxiety: effect of behavioural
      and pharmacological hyperadrenergic stimulation on APO-induced erections.
AB  - As part of the multifactorial nature of erectile dysfunction, anxiety associated
      with sexual performance (SPA) remains a major contributing factor to its
      progression. In fact, the heightened sympathetic activity associated with sexual
      performance anxiety may be a key early component of this disruption of normal
      erectile responses. We are not aware that any animal models have been developed
      to assess this phenomenon. Using apomorphine (APO, 80 microg/kg s.c.)-induced
      erections in rats we characterised the effects of behavioural or pharmacological
      hyperadrenergic stimulation (that is, anxiety) on erections and hemodynamics. We
      developed an experimental SPA paradigm by exposing male rats to the stress of
      being observed by a larger, older male rat placed in close proximity to test rats
      during APO testing. In a separate group, adrenergic stress was simulated using a
      sympathomimetic, methoxamine (MXA) given prior to APO testing. In a third group,
      the changes in circulatory parameters (mean arterial pressure, heart rate) were
      determined following instrumentation with radiotelemetric transducers for each
      scenario. APO-induced erections were significantly lower in both the behavioural
      (1.25+/-0.8) and pharmacological (0.33+/-0.5) stressor paradigms compared to
      controls (2.81+/-0.9). Further, erections in MXA-treated rats were significantly
      lower than in the observed scenario. Despite the differences in erections
      hemodynamic assessments showed no differences in MAP or HR changes between the
      different experimental conditions. Thus, both the behavioural and pharmacological
      paradigms of SPA decreased erections, but did not affect the circulation. This
      suggests that the level of hyperadrenergic input required to induce erectile
      dysfunction can be subtle, and target only erectogenic pathways.

PMID- 11979327
TI  - Validation of a continuous penile blood-flow measurement by pulse-volume
      plethysmography.
AB  - Today, in the assessment of cavernous artery blood-flow, the most commonly used
      technique is Doppler ultrasound velocimetry (continuous, pulsed, color-coded or
      power), which is often considered as the gold standard. Plethysmographic
      techniques and radioactive tracers have been widely used for the assessment of
      global penis flow variations but are not adequate for continuous blood-flow
      measurement. A new pulse-volume plethysmographic (PVP) device using a water
      filled penile cuff was employed to assess continuous blood-flow measurement in
      the penis. Simultaneously Doppler velocity was recorded and served as a gold
      standard. A penile water-cuff is connected through a pressure tube to a three-way
      tap. The pulse-volume changes in the penile water-cuff are measured by means of a
      latex membrane placed over one of the three-way taps. The displacements of the
      latex are recorded by a photoplethysmograph. The third tap is connected to a 5 l
      perfusion bag placed 30 cm above the penis so as to maintain constant pressure in
      the whole device whatever the penis volume. Twenty-four volunteers were tested.
      The Doppler velocity signal and pulse volume of cavernous arteries were measured
      simultaneously after PGE1 intra-cavernous injection. Blood-flow variations were
      induced by increasing penis artery compression with a second penile water-cuff
      used as a tourniquet fitted onto the penis root, and the pressure of which could
      be modified by a water-filled syringe. The amplitude of the plethysmographic
      pulse-volume signal and the area under the Doppler velocity signal were
      correlated. The inter-patient (n=24) correlation ranged from 0.455 to 0.904, with
      a mean correlation of 0.704 and P<0.0001. PVP measurement by a water-filled cuff
      was validated by ultrasound velocimetry. This new continuous, non-invasive and
      easy-to-use technique enables physiological and physiopathological flow
      measurement during sleep, under visual sexual stimulation (VSS), or following
      artificial erection. Simultaneous recording of penile blood-flow by PVP and intra
      cavernous pressure (ICP) measured by a non-invasive device will provide
      fundamental inflow and outflow information in both physiological and
      pathophysiological conditions, and further enable venous leakage to be assessed
      by a mathematical model.

PMID- 11979328
TI  - Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum
      tissue: synergism of nitric oxide and YC-1.
AB  - Nitric oxide (NO) activates corpus cavernosum smooth muscle soluble guanylate
      cyclase (sGC) and increases the synthesis of cGMP that results in smooth muscle
      relaxation and ultimately, penile erection. To characterize sGC and define the
      potential synergy between NO and the allosteric activator YC-1 in corpus
      cavernosum, rat sGC was activated by either sodium nitroprusside (SNP) or YC-1,
      and YC-1 potentiated the effects of SNP with a 200-fold activation of sGC. Both
      SNP and YC-1 decreased the Km and increased the Vmax. ODQ significantly inhibited
      sGC activated by SNP with IC50 of 0.5 nM, but did not affect the sGC activated by
      YC-1 as well as basal sGC activity. SNP and YC-1 synergistically increased
      intracellular cGMP levels in rabbit corpus cavernosum smooth muscle cell
      cultures. YC-1 significantly relaxed rabbit cavernosum tissue strips in organ
      baths with an EC50 of 8.4 microM. In the presence of L-nitroarginine methyl ester
      to block endogenous NO production, co-administration of SNP shifted the dose
      response of YC-1 to the left, showing the synergism of SNP and YC-1 in tissue
      strips. In view of the clinical efficacy of phosphodiesterase-5 inhibitors,
      activation of sGC may provide an alternative means for enhancing the activity of
      neurally derived NO during sexual stimulation in the corpus cavernosum,
      representing a novel approach for the treatment of erectile dysfunction.

PMID- 11979329
TI  - Effect of apomorphine on intracavernous pressure and blood pressure in conscious,
      spinalized rats.
AB  - Apomorphine, given subcutaneously (s.c.), induces erection and bladder
      overactivity in rats through stimulation of dopamine (D1- and D2-like) receptors
      in the central nervous system. In paraplegic patients, apomorphine was reported
      to cause bladder overactivity. This suggests that apomorphine may have a spinal
      site of action also for stimulation of erection. The present study was initiated
      to evaluate the effect of apomorphine on erectile function in spinalized rats.
      Apomorphine (100 microg/kg, s.c.) was given to awake, unrestrained male Sprague
      Dawley rats (300 g) with or without spinal cord injury, made at the Th 8 level 2
      weeks before the experiment. Intracavernous pressure changes from baseline were
      evaluated as time to first response to apomorphine (TFR; sec), number of phasic
      pressure changes in the first 30 min (PP30), duration (D; sec) of the phasic
      pressure changes, the amount of increase in tonic peak pressure (TPP; cmH2O), and
      burst peak pressure (BPP; cmH2O). Blood pressure (cmH2O) was recorded via an
      intra-arterial catheter. Apomorphine, 100 microg/kg, caused no significant
      differences in TFR (217.8 vs 271.2), PP30 (6.4 vs 6.5), D (38.9 vs 37.6.), TPP
      (51.0 vs 54.0) and BPP (128.9 vs 160.4) between normal (n=8) and spinalized rats
      (n=6). However, blood pressure decreased significantly more in spinalized than in
      normal animals (17.7 vs 43.3; P<0.05). The results suggest that both in normal
      rats, and in rats with spinal cord injury, apomorphine given s.c., can produce
      erection. This finding supports the use of apomorphine for treatment of erectile
      dysfunction in paraplegia patients. However, due consideration should be given to
      possible decreases in blood pressure.

PMID- 11979330
TI  - Absence of orgasm-induced prolactin secretion in a healthy multi-orgasmic male
      subject.
AB  - In several studies we have recently demonstrated that orgasm induces prolactin
      secretion in healthy males and females. This suggests that prolactin may form a
      feedback regulator of the refractory period following orgasm. To examine this
      position we investigated the prolactin response of a healthy multi-orgasmic male
      subject. Blood was drawn continuously during masturbation-induced orgasm. The
      prolactin response of the case-subject was compared with that of nine healthy
      adult men with a normal refractory period. The case-subject showed no prolactin
      response to three orgasms. Data from this multi-orgasmic subject support the
      hypothesized role of plasma prolactin in contributing to sexual-satiation
      mechanisms.

PMID- 11979331
TI  - 'Sildenafil and pharmaco-penile duplex ultrasonography' by Speel et al:
      inconclusive results.

PMID- 11979333
TI  - Goodpasture syndrome during the course of a Schonlein-Henoch purpura.
AB  - Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old
      patient presented with Schonlein-Henoch purpura with kidney involvement followed
      by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney
      biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA
      antibodies led to the diagnosis of Goodpasture syndrome, which implies the
      possibility that the well-known pulmonary involvement during the course of
      Schonlein-Henoch purpura could be caused by Goodpasture syndrome in certain
      cases. In cases of glomerulonephropathy with lung involvement, clinicians should
      not limit their investigations to anti-GBM IgG.

PMID- 11979334
TI  - Renal handling of albumin: a critical review of basic concepts and perspective.
AB  - Biochemical and physiological processes that underlie the mechanism of
      albuminuria are completely reassessed in this article in view of recent
      discoveries that filtered proteins undergo rapid degradation during renal passage
      and the resulting excreted peptide fragments are not detected by conventional
      urine protein assays. This means that filtered protein and/or albumin levels in
      urine have been seriously underestimated. The concept that albuminuria is a
      result of changes in glomerular permeability is questioned in light of these
      findings and also in terms of a critical examination of charge selectivity,
      shunts, or large-pore formation and hemodynamic effects. The glomerulus appears
      to function merely in terms of size selectivity alone, and for albumin, this does
      not change significantly in disease states. Intensive albumin processing by a
      living kidney occurs through cellular processes distal to the glomerular basement
      membrane. Failure of this cellular processing primarily leads to albuminuria.
      This review brings together recent data about urinary albumin clearance and
      current knowledge of receptors known to process albumin in both health and
      disease states. We conclude with a discussion of topical and controversial issues
      associated with the proposed new understanding of renal handling of albumin.

PMID- 11979335
TI  - Calibration and random variation of the serum creatinine assay as critical
      elements of using equations to estimate glomerular filtration rate.
AB  - Equations using serum creatinine level, age, sex, and other patient
      characteristics often are used to estimate glomerular filtration rate (GFR) in
      both clinical practice and research studies. However, the critical dependence of
      these equations on serum creatinine assay calibration often is overlooked, and
      the reproducibility of estimated GFR is rarely discussed. We address these issues
      in frozen samples from 212 Modification of Diet in Renal Disease (MDRD) study
      participants and 342 Third National Health and Nutrition Examination Survey
      (NHANES III) participants assayed for serum creatinine level a second time during
      November 2000. Variation in serum creatinine level was assessed in 1,919 NHANES
      III participants who had serum creatinine measured on two visits a median of 17
      days apart. Linear regression was used to compare estimates. Calibration of serum
      creatinine varied substantially across laboratories and time. Data indicate that
      serum creatinine assays on the same samples were 0.23 mg/dL higher in the NHANES
      III than MDRD study. Data from the College of American Pathologists suggest that
      a difference of this magnitude across laboratories is not unusual. Conversely,
      serum creatinine assays an average of 2 weeks apart have better precision (SD of
      percentage of difference in estimated GFR, 15%; 90% of estimates within 21%).
      Errors in calibration make little difference in estimating severely decreased GFR
      (<30 mL/min/1.73 m2), but result in progressively larger differences at higher
      GFRs. Both clinical and research use of serum creatinine or equations to estimate
      GFR require knowledge of the calibration of the serum creatinine assay.

PMID- 11979336
TI  - Hospital-acquired renal insufficiency.
AB  - Despite myriad improvements in the care of hospitalized patients, a decline in
      renal function remains a common event. Renal function in 4,622 consecutive
      patients admitted to the medical and surgical services of an urban tertiary care
      hospital was followed up prospectively from the time of admission. Some degree of
      renal insufficiency developed in 7.2% of patients. Decreased renal perfusion,
      medications, surgery, and radiographic contrast media were the most common causes
      of hospital-acquired renal insufficiency (HARI). The overall mortality rate was
      19.4% and was similar among patients for all causes of renal insufficiency,
      except sepsis. For patients with a greater than 3.0-mg/dL increase in serum
      creatinine level, the mortality rate was 37.8%. As shown by previous
      investigators, age and preexisting renal insufficiency were risk factors for
      HARI. Women and blacks had less hospital-acquired renal failure. The increasing
      acuity of hospital admissions has been accompanied by a greater incidence of
      acute renal insufficiency in patients admitted to hospitals. There is a trend
      toward better survival in patients with a severe deterioration in renal function.

PMID- 11979337
TI  - Endotoxin removal by direct hemoperfusion with an adsorbent column using
      polymyxin B-immobilized fiber ameliorates systemic circulatory disturbance in
      patients with septic shock.
AB  - Direct hemoperfusion (DHP) with an adsorbent column using polymyxin B-immobilized
      fiber (PMX-F) has been shown to improve the state of shock in patients with
      septic shock. However, no evidence has been presented for a direct link between
      endotoxin removal by DHP with PMX-F and improvement in septic shock. We
      retrospectively analyzed clinical profiles of 24 patients with septic shock (16
      patients, gram-negative; 8 patients, non-gram-negative septic shock) who
      underwent DHP with PMX-F. Patients with gram-negative septic shock were
      characterized by hyperdynamic circulation. DHP with PMX-F reduced blood endotoxin
      concentrations and ameliorated shock, with an improvement in hyperdynamic
      circulation in patients with gram-negative septic shock. Mean arterial pressure
      also was elevated after therapy in patients with non-gram-negative septic shock,
      but systemic hemodynamics were unaffected. Regardless of the causative
      microorganism, patients with endotoxemia (blood endotoxin level > 10 pg/mL)
      showed hyperdynamic shock, and DHP with PMX-F reduced blood endotoxin levels and
      ameliorated hyperdynamic circulation, whereas patients without endotoxemia showed
      features of shock without hyperdynamic circulation, and DHP with PMX-F
      ameliorated shock without affecting cardiac performance. In patients with gram
      negative septic shock, blood endotoxin concentration correlated positively with
      cardiac output and negatively with systemic vascular resistance before DHP
      therapy. Reduction in blood endotoxin concentration by DHP therapy positively
      correlated with the reduction in cardiac output. Our findings indicate that the
      improvement in hyperdynamic circulation was related directly to endotoxin removal
      by the PMX-F column, and endotoxin has an important role in the development of
      hyperdynamic circulation in patients with gram-negative septic shock.

PMID- 11979338
TI  - Quantitative analyses of osteopontin mRNA expression in human proximal tubules
      isolated from renal biopsy tissue sections of minimal change nephrotic syndrome
      and IgA glomerulonephropathy patients.
AB  - Osteopontin (OPN), a secreted phosphoprotein and chemotactic to
      monocytes/macrophages, is upregulated in renal cortical tubules in a variety of
      rodent models of renal injury and is believed to possibly have a role in
      tubulointerstitial injury. We previously reported the establishment of a system
      for the quantification of messenger RNA (mRNA) expression in isolated rat
      glomeruli using laser-manipulated microdissection and real-time polymerase chain
      reaction. This system was applied to human renal biopsy specimens. We quantified
      OPN mRNA expression in proximal tubules of 5 patients with minimal change
      nephrotic syndrome (MCNS) and 11 patients with mild immunoglobulin A (IgA)
      glomerulonephritis. We also examined the correlation between OPN mRNA expression
      in proximal tubules and clinical data and pathological findings in glomeruli and
      tubulointerstitial regions. Patients with MCNS showed a positive correlation
      between OPN mRNA expression in proximal tubules and urinary protein excretion (r
      = 0.93; P < 0.05), whereas for patients with IgA glomerulonephritis, logarithmic
      values of OPN mRNA expression in proximal tubules positively correlated with low
      urinary protein levels (r = 0.72; P < 0.05). Pathological changes, ranging from
      nonexistent to minor, in glomeruli and tubulointerstitium of these patients with
      mild IgA glomerulonephritis did not significantly correlate with OPN mRNA
      expression in proximal tubules. In patients with mild IgA glomerulonephritis, OPN
      mRNA expression in proximal tubules increased exponentially in response to a
      small amount of urinary protein (<1.2 g/d).

PMID- 11979339
TI  - T-lymphocyte populations and cytokines in childhood nephrotic syndrome.
AB  - We investigated lymphocyte subpopulations and the production of cytokines by T
      helper cell subtype 1 (Th1), Th2, and monocytes/macrophages (tumor necrosis
      factor-alpha [TNF-alpha]) in peripheral-blood mononuclear cells of 18 children
      with steroid-sensitive (SS) nephrotic syndrome (NS) and 10 children with steroid
      resistant (SR) NS. Mean age was 10.9 +/- 5.7 years, with a mean follow-up before
      the study of 6 +/- 5 years. To evaluate the possible relationship between
      cytokine levels and response to treatment, patients with SS and SR NS were
      assessed during relapse/marked proteinuria (group A), total/partial remission
      (group B), and off treatment (group C). In children with SS and SR NS, we found
      no significant difference in CD3 counts compared with controls. The proportion of
      CD4 cells decreased significantly in relapse and off therapy compared with
      controls in children with SS NS, whereas in those with SR NS, there was a
      concomitant reduction in all groups. B-Lymphocyte counts were significantly
      increased in either group versus controls. In SR NS, CD8 and natural killer cell
      levels increased during relapse versus controls. The CD4+/CD8+ ratio was reduced
      to the same degree in those with SS and SR NS. In patients with SR NS, we
      observed increased levels of soluble interleukin-2 (IL-2) receptor (sIL-2R) from
      corresponding control values (P < 0.01). A significant increase in TNF-alpha
      levels was found in patients with SS and SR NS versus controls. High levels of IL
      2, sIL-2R, and interferon-gamma during relapse in patients with SS NS give
      further evidence for a Th1 pattern that might be involved in the pathogenesis of
      NS, and monitoring the Th1/Th2 balance would be useful in evaluating the response
      to therapy.

PMID- 11979340
TI  - Reduction of postembolization syndrome after ablation of renal angiomyolipoma.
AB  - Approximately 75% of patients with tuberous sclerosis complex develop renal
      angiomyolipomas. These hamartomatous lesions distort and damage renal parenchyma
      and can lead to hemorrhage. To reduce the risk of hemorrhage, transarterial
      embolization is used to necrose the angiomyolipoma while sparing normal renal
      tissue. Although an effective renal-sparing procedure, embolization most often is
      associated with an inflammatory response that causes significant fever and pain
      that can last for several days despite the use of acetaminophen. Reported cases
      show that 49 of 55 patients who underwent embolization developed this syndrome.
      The use of such nonsteroidal anti-inflammatory drugs as aspirin is
      contraindicated because of their adverse effects on platelet function. To reduce
      pain and fever associated with postembolization syndrome (PES), we changed our
      clinical management of patients postembolization to include a tapering dose of
      prednisone over a 2-week period. Nine patients underwent this pharmacological
      intervention, and one patient abstained. All patients were monitored for pain and
      fever. Only two patients treated with steroids developed fever, which was
      assuaged with acetaminophen, and no patient reported pain. The tapering dose of
      prednisone was well tolerated, and there were no postprocedure infections. The
      use of a short-term tapering dose of prednisone appeared to reduce PES compared
      with the reported literature and improved patient comfort.

PMID- 11979341
TI  - Small-sized low-density lipoproteins of subclass B from patients with end-stage
      renal disease effectively augment tumor necrosis factor-alpha-induced adhesive
      properties in human endothelial cells.
AB  - Increased prevalence of small-sized low-density lipoprotein (LDL) subclass B
      (diameter < 25.5 nm) possibly is involved in the multifactorial process of
      cardiovascular disease in patients with end-stage renal disease. Given these
      epidemiological observations, mechanisms underlying the combined effect of a
      proinflammatory insult and LDL of different subclasses (subclass A, diameter >
      25.5 nm, and subclass B) in a cellular model were investigated. For this, human
      umbilical vein endothelial cells were preexposed to LDL, then stimulated with
      tumor necrosis factor-alpha (TNF-alpha). Modulatory effects of LDL phenotypes on
      the activation of adhesion molecules, monocyte adherence, and transcriptional
      activity of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) were
      investigated. Our data show that subclass B LDLs were metabolized through
      nonspecific scavenger receptors and specific LDL-receptor pathways in endothelial
      cells. Furthermore, LDL subclass B in comparison to subclass A more effectively
      enhanced monocyte recruitment and adhesive properties of endothelial cells in
      response to TNF-alpha. These effects appeared not to be mediated by oxidative
      stress-responsive NF-kappaB because modulation of this transcription factor by
      LDL was moderate and similar for both LDL phenotypes. Conversely, effects of LDL
      subclass B were considered to be caused by augmented AP-1 binding activity. In
      conclusion, the present model provides new clues in atherogenic mechanisms of
      small-sized LDLs, which sensitize vascular cells to inflammatory signals more
      effectively than normal-sized LDLs.

PMID- 11979342
TI  - Goto-Kakizaki rat is protected from proteinuria after induction of anti-Thy1
      nephritis.
AB  - Hyperglycemia, although necessary, alone is insufficient for the development of
      progressive diabetic nephropathy. Two factors implicated in its pathogenesis are
      mesangial cell activation and/or proliferation and monocyte/macrophage influx. We
      have shown that prolonged hyperglycemia in the Goto-Kakizaki (GK) rat is
      associated with renal structural changes similar to those in patients with
      diabetes before the onset of progressive nephropathy. The aim of the current
      study is to examine the role of mesangial cell injury and macrophage influx on
      renal structure and function. After induction of nephritis in either
      hyperglycemic GK rats or normoglycemic Wistar rats by the administration of Ox-7
      antibody, the degree of mesangiolysis and subsequent mesangial proliferation was
      no different between GK and Wistar rats. Similarly, macrophage influx and
      mesangial cell activation (assessed by alpha-smooth actin expression) was no
      different between the two groups. Wistar rats developed marked albuminuria;
      conversely, no significant proteinuria or albuminuria was seen in GK rats.
      Analysis of glomerular proteoglycans (PGs) showed an increase in (35)S
      incorporation into heparan sulfate PGs of GK compared with Wistar rats, with no
      alteration in glycosaminoglycan chain size or charge density. These changes were
      kidney specific and not seen in spleen, lung, or heart tissue. Western blot
      analysis showed increased agrin core protein expression in whole-kidney
      homogenates of untreated GK rats. Induction of Thy1.1 nephritis was associated
      with reduced expression of agrin in both GK and Wistar rats. However, agrin
      expression was greater in GK rats at all times. In summary, acute mesangial cell
      injury associated with a macrophage influx did not initiate progressive diabetic
      nephropathy in GK rats. Despite a similar magnitude of glomerular/mesangial
      injury, GK rats, in contrast to normoglycemic Wistar rats, did not develop
      proteinuria after the administration of anti-Thy1 antibody. We postulate that
      altered expression of agrin in this model accounts for the lack of proteinuria
      and thus may protect against progressive nephropathy.

PMID- 11979343
TI  - Glucocorticoid diminishes vascular endothelial growth factor and exacerbates
      proteinuria in rats with mesangial proliferative glomerulonephritis.
AB  - Glucocorticoids are widely prescribed for renal diseases. It is believed that
      glucocorticoids attenuate immune-mediated renal diseases by suppressing the cell
      mediated immune system. However, there is evidence that glucocorticoids influence
      the expression of such growth factors as vascular endothelial growth factor
      (VEGF), transforming growth factor-beta1 (TGF-beta1), and connective tissue
      growth factor (CTGF), which are known to influence the development or progression
      of renal diseases. Therefore, we undertook this study to determine whether
      glucocorticoids regulate proteinuria or extracellular matrix (ECM) production by
      altering these growth factors. Mesangial proliferative glomerulonephritis was
      induced in rats by intravenous injection of monoclonal antibody (OX-7), and
      dexamethasone (20 mg/kg) was administered intraperitoneally from the third to
      seventh disease day. Glomerular expression of VEGF, TGF-beta1, and CTGF, the
      amount of urinary protein, and glomerular ECM were measured on the seventh
      disease day. The nephritic group showed proteinuria and greater VEGF, TGF-beta1,
      and ECM production. Dexamethasone aggravated proteinuria (protein, 0.4 +/- 0.1
      mg/mg creatinine in the NC group, 6.3 +/- 2.0 mg/mg creatinine in the DC group,
      and 21.1 +/- 1.9 mg/mg creatinine in the D-Dex group; P < 0.05) and diminished
      VEGF release (22 +/- 3 pg/mg total protein in the NC group, 292 +/- 26 pg/mg
      total protein in the DC group, and 198 +/- 23 pg/mg total protein in the D-Dex
      group; P < 0.05). Expression of TGF-beta1, CTGF, and ECM was not altered
      significantly by dexamethasone treatment. We found that glucocorticoid diminishes
      VEGF release and at the same time exacerbates proteinuria in rats with this type
      of glomerulonephritis.

PMID- 11979344
TI  - Chronic dialysis patients have high risk for pulmonary embolism.
AB  - Pulmonary embolism has been considered uncommon in chronic dialysis patients, but
      has not been adequately studied in a large population. In the US Renal Data
      System (USRDS), 76,718 patients presenting with end-stage renal disease (ESRD)
      between January 1, 1996, and December 31, 1996, were analyzed in an historical
      cohort study. The outcome was hospitalizations with a primary discharge diagnosis
      of pulmonary embolism (International Classification of Diseases, Ninth Revision
      code 415.1x) occurring within 1 year of the first ESRD treatment and excluding
      those occurring after renal transplantation. For dialysis patients,
      hospitalization rates for pulmonary embolism were obtained from the
      hospitalization section of the 1999 USRDS. For the general population,
      hospitalization rates for pulmonary embolism were obtained from the National
      Hospital Discharge Survey for 1996. Comorbidities from the Medical Evidence Form
      (Centers for Medicare and Medicaid Services, previously known as the Health Care
      Financing Administration; form 2728) were used to generate approximated
      stratified models of adjusted incidence ratios for pulmonary embolism
      (comorbidities could not be stratified for the general population). In 1996, the
      overall incidence rate of pulmonary embolism was 149.90/100,000 dialysis patients
      compared with 24.62/100,000 persons in the US population, with an age-adjusted
      incidence ratio of 2.34 in dialysis patients. Younger dialysis patients had the
      greatest relative risk for pulmonary embolism. The age-adjusted incidence ratio
      of pulmonary embolism after excluding dialysis patients with known risk factors
      for pulmonary embolism was 2.11. Ninety-five percent confidence intervals for all
      age categories in both models were statistically significant. Chronic dialysis
      patients have high risk for pulmonary embolism, independent of comorbidity.

PMID- 11979345
TI  - Association of fish intake and survival in a cohort of incident dialysis
      patients.
AB  - Multiple studies in the general population have shown cardioprotective and
      survival benefits associated with dietary fish intake, but little is known about
      outcomes associated with dietary fish intake in patients with chronic renal
      failure. We investigated fish consumption and survival in 216 incident dialysis
      patients. Fish consumption was identified in a 24-hour dietary recall and a 3-day
      food diary collected at baseline (near treatment start) and a 3-day food diary
      collected 1 year later. Patients who reported fish intake had higher average
      serum albumin levels at baseline than patients who did not report fish intake.
      Patient survival was followed up for an average of 3 years from baseline. In
      univariate Cox regression models, younger age, black race, peritoneal dialysis
      rather than hemodialysis as initial treatment modality, absence of cardiovascular
      comorbidity, higher self-assessed physical functioning, and fish consumption were
      significantly associated with patient survival. A multivariable Cox proportional
      hazards regression analysis showed that dietary fish consumption independently
      predicted patient survival, controlling for all other variables in the model. In
      multivariable analysis, patients who were younger, black, and had higher mental
      health scores at baseline also had a significantly decreased mortality risk.
      Patients who reported fish consumption were approximately 50% less likely to die
      during the study interval. Health outcomes associated with fish consumption merit
      continued study in patients with chronic renal failure.

PMID- 11979346
TI  - Skeletal muscle mitochondrial function is preserved in young patients with
      chronic renal failure.
AB  - Patients with chronic renal failure (CRF) show limited exercise tolerance,
      classically attributed to anemia. However, persistence of abnormally low peak
      oxygen consumption, even after restoration of hemoglobin concentration with
      recombinant erythropoietin therapy and studies of muscle bioenergetics, suggests
      that the problem is located beyond hemoglobin oxygen transport. The present study
      is designed to assess mitochondrial respiratory chain (MRC) function from
      skeletal muscle of patients with CRF to determine whether there is impairment in
      mitochondrial oxidative capacity. We studied six young patients with CRF on
      regular hemodialysis and erythropoietin therapy and six healthy controls matched
      by age, sex, anthropometric characteristics, and physical activity. Muscle biopsy
      of the quadriceps was performed, and mitochondria were isolated. Mitochondrial
      content was estimated by means of mitochondrial yield and citrate synthase
      activity. Maximal capacity for oxygen consumption was measured polarographically
      using complex I, II, III, and IV substrates of the MRC. Individual enzyme
      activities of MRC complexes I to V were determined spectrophotometrically.
      Membrane lipid peroxidation was estimated by cis-parinaric fluorescence. Compared
      with controls, patients with CRF showed preserved mitochondrial content,
      conserved respiratory activity, intact enzyme activity of MRC complexes, and no
      increase in lipid peroxidation. We therefore conclude that mitochondrial function
      is preserved in young patients with CRF.

PMID- 11979347
TI  - Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence
      plasma homocysteine in hemodialysis patients.
AB  - Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent
      in hemodialysis (HD) patients. A common polymorphism in the 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at
      nucleotide 677, is associated with homocysteine (Hcy) level elevation. We
      examined whether three factors involved in the methionine cycle could influence
      plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an
      essential cofactor; and folate, the substrate. In a cross-sectional study, serum
      vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was
      performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate
      on plasma Hcy levels were examined in 450 HD patients not administered vitamin
      B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations,
      we compared plasma Hcy concentrations in HD patients with and without vitamin B12
      supplementation. To examine whether functional vitamin B12 deficiency exists even
      in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum
      vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12
      (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid
      (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels
      were lower in patients with the TT and CT genotypes compared with patients with
      the CC genotype. Analysis of covariance to determine independent predictors of
      high Hcy levels identified low serum vitamin B12 and folate levels and high
      albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb
      levels in CT-genotype patients, and low folate levels in TT-genotype patients.
      Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12
      supplementation than in those without supplementation. Vitamin B12
      supplementation for 8 weeks significantly reduced MMA concentrations in HD
      patients with normal serum vitamin B12 concentrations. These results indicate
      that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and
      folate levels in HD patients. Functional vitamin B12 deficiency may exist, even
      in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin
      B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

PMID- 11979348
TI  - Useful markers for detecting decreased serum antioxidant activity in hemodialysis
      patients.
AB  - This study evaluates a novel application of a method for measuring serum
      antioxidant activity, based on the detection of erythrocyte membrane lipid
      peroxidation in cases of uremia. A human erythrocyte ghost membrane in Tris-HCl
      was mixed with adenosine 5'-diphosphate and iron chloride (FeCl3; ADP/Fe3+)
      solution (at a molar ratio of 17:1), and the mixture was incubated under aerobic
      conditions at 37 degrees C for 2 hours. The concentration of erythrocyte membrane
      thiobarbituric acid-reactive substances increased proportionally with respect to
      ADP/Fe3+ concentration, and this increase was inhibited by serum albumin in a
      dose-dependent manner. In patients undergoing chronic hemodialysis therapy,
      predialytic sera contained in this reaction mixture were weaker than postdialytic
      sera in terms of inhibitory effect against erythrocyte membrane lipid
      peroxidation, whereas serum albumin contents remained at levels equivalent to
      those of the normal control. A gradual increase in human mercaptalbumin
      nonmercaptalbumin ratio during hemodialysis treatment might be one of the major
      factors that leads to the recovery of decreased serum antioxidant activity. We
      clearly showed that the serum scavenging activity against erythrocyte membrane
      lipid peroxidation in hemodialysis patients decreases markedly, and this
      pathological condition is improved by hemodialysis.

PMID- 11979349
TI  - Dialyzer fiber bundle volume and kinetics of solute removal in continuous
      venovenous hemodialysis.
AB  - The relationship between dialyzer fiber bundle volume (FBV), dialyzer life span,
      and small-solute clearance has yet to be clearly defined in continuous venovenous
      hemodialysis (CVVHD). This study sought to define this relationship using novel
      ultrasound dilution technology. We studied 55 sessions in 31 intensive care unit
      patients on CVVHD therapy. A session was defined as the life span of a single
      dialyzer. The following variables were assessed every 6 hours throughout each
      session, starting within 1 hour of initiation of that session: FBV, access
      recirculation, extracorporeal blood flow rate, effluent (EUN) to blood urea
      nitrogen (BUN) concentration ratio, effluent creatinine to blood creatinine
      concentration ratio, and urea nitrogen and creatinine clearances. Data were
      analyzed using random-effects linear models to estimate trends. Several dialysis
      related and solute-removal parameters were analyzed for association with each
      other. Systemic or dialysis circuit heparin was administered in 28 of 55
      sessions. One hundred seventy sets of FBV, 101 sets of urea clearance, and 102
      sets of creatinine clearance measurements were performed. There was a declining
      trend for FBV (0.8 mL/h), heart rate (0.25 beats/min/h), and measured blood flow
      (0.33 mL/min/h; P < 0.05). Apart from dialysate inflow rate (P = 0.044), there
      was no significant correlation with EUN-BUN ratio. Session duration was
      associated with dialysis access site; the femoral access provided longer dialysis
      sessions than subclavian and internal jugular accesses (P = 0.029). We conclude
      that small-solute removal remains stable over the course of our CVVHD system life
      spans despite significant loss of hemodialyzer FBV.

PMID- 11979350
TI  - Prognostic role of serum ACE activity on outcome of type 2 diabetic patients on
      chronic ambulatory peritoneal dialysis.
AB  - Overexpression of the renin-angiotensin system is important in the pathogenesis
      of macroangiopathy (MA). Patients with diabetes with end-stage renal failure have
      elevated serum angiotensin-converting enzyme (ACE) activity compared with their
      nonuremic counterparts. Because their major cause of death is MA, the
      significance of serum ACE activity on outcome of this group of patients is
      studied. We performed a prospective cohort study of 49 patients with type 2
      diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Baseline
      serum ACE activity was determined by a modified spectrophotometric method and
      followed up at a median of 34 months. The prevalence of MA (defined as ischemic
      heart disease, sudden cardiac arrest, stroke, or peripheral vascular disease) and
      all-cause mortality rates were studied. Risk for MA is associated with serum ACE
      activity (median with MA, 69.0 U/L [range, 46.0 to 100.1 U/L] versus without MA,
      57.2 U/L [range, 36.3 to 81.0 U/L]; P = 0.02). At the end of follow-up, 48% of
      patients (24 of 49 patients) died, 70% of MA. The group that died had increased
      baseline serum ACE activity (nonsurvivors, 65.0 U/L [range, 33.5 to 100.0 U/L]
      versus survivors, 49.4 U/L [range, 36.4 to 86.5 U/L]; P < 0.05) and MA rates
      (nonsurvivors, 77% versus survivors, 36%; P < 0.01). Cox regression analysis
      performed with age, sex, mean blood pressure, body mass index, metabolic control,
      Kt/V, residual renal function, serum albumin level, and ACE activity showed that
      baseline serum ACE activity (P = 0.033) is an independent predictor for mortality
      in patients with type 2 diabetes on CAPD therapy. Among patients with type 2
      diabetes on CAPD therapy, serum ACE activity is associated with risk for MA and
      is an independent predictor for mortality. Whether ACE inhibition will have a
      beneficial effect on the outcome of these patients needs further investigation.

PMID- 11979351
TI  - Plasminogen activator inhibitor-1 4G/5G genetic polymorphism does not affect
      peritoneal transport characteristic.
AB  - There is evidence that type 1 plasminogen activator inhibitor (PAI-1) may have an
      important role in peritoneal function. We studied the effect of physiologically
      relevant PAI-1 promotor polymorphisms on peritoneal permeability. We performed a
      standard peritoneal equilibration test (PET) in 100 new continuous ambulatory
      peritoneal dialysis (CAPD) patients. We studied another 48 prevalent CAPD
      patients who had a baseline PET performed 2 years before; a standard PET was
      repeated on enrollment. The PAI-1 promotor polymorphism was examined. All
      patients then were followed up for 16.7 +/- 15.0 months. Prevalences of 4G/4G,
      4G/5G, and 5G/5G genotypes were 31.8%, 46.6%, and 21.6%, respectively. Of the 100
      new CAPD patients, there was no difference in net ultrafiltration (UF), dialysate
      plasma (D/P) creatinine ratio at 4 hours, or mass transfer area coefficient
      (MTAC) of creatinine among the three genotype groups. D/P creatinine ratios at 4
      hours were 0.595 +/- 0.133, 0.607 +/- 0.137, and 0.627 +/- 0.142 for the 4G/4G,
      4G/5G, and 5G/5G groups, respectively (one way analysis of variance, P = 0.715).
      Of the 48 prevalent patients, PAI-1 genotype did not affect the longitudinal
      change in net UF, D/P creatinine ratio at 4 hours, or MTAC of creatinine. During
      follow-up, 16 patients developed peritonitis episodes that required Tenckhoff
      catheter removal. One patient died, 8 patients returned to long-term CAPD therapy
      after peritonitis resolved, and the other 7 patients developed peritoneal failure
      and were switched to long-term hemodialysis therapy. PAI-1 promotor genotype did
      not predict peritoneal failure after an episode of severe peritonitis (chi-square
      test, P = 0.328). We conclude that PAI-1 promotor polymorphism is not associated
      with peritoneal transport characteristics in stable peritoneal dialysis patients,
      longitudinal change in peritoneal transport, or development of peritoneal failure
      after an episode of severe peritonitis.

PMID- 11979352
TI  - Weight deficit in patients on continuous ambulatory peritoneal dialysis.
AB  - Small solute clearances were compared between two groups of patients on
      continuous ambulatory peritoneal dialysis (CAPD), an underweight group with a
      ratio of actual-to-ideal weight (W/IW) less than 0.9 and a normal-weight group
      with W/IW between 0.9 and 1.2 at the first clearance study after initiation of
      CAPD. Adequate clearance levels were set according to the K/DOQI guidelines.
      Duration of follow-up during CAPD and time on CAPD until the first clearance
      study was similar in the two groups. Initial weekly Kt/V urea and creatinine
      clearance also were similar. Kt/V urea values were adequate in 41.8% of the
      underweight subjects and 41.0% of the normal-weight subjects (not significant).
      Corresponding percentages for creatinine clearance were 36.4% and 39.7% (not
      significant). Serum creatinine and albumin concentration, creatinine excretion,
      and lean body mass estimated from creatinine kinetics were lower in the
      underweight group. Weight measurements from initiation of CAPD were available in
      37 underweight patients. At initiation of CAPD, 31 subjects had W/IW less than
      0.9, and 6 subjects had W/IW greater than 0.9. Chronic catabolic illness was
      present at CAPD initiation in 19 patients. Among the 37 patients, 17 lost weight
      and 6 gained weight during the course of CAPD. Compared with patients who lost
      weight, those who gained weight were younger (35.6 +/- 9.3 years old versus 58.4
      +/- 15.0 years old; P = 0.0069) and had a higher percent of women (80.0% versus
      11.8%; P = 0.0093), higher initial weekly Kt/V urea (2.58 +/- 0.50 versus 1.91 +/
      0.24; P = 0.0087), and a higher percent of adequate Kt/V urea (80.0% versus
      11.8%; P = 0.0093). Small solute clearances do not differ between underweight
      CAPD patients and normal-weight CAPD patients. Underweight CAPD patients usually
      start CAPD with a weight deficit and have associated catabolic illnesses.
      Catabolic illness is the sole cause of weight deficit in 40% of the underweight
      CAPD patients and is present in the remaining 60%. The role of inadequate
      clearances in the development of weight deficit in CAPD populations is difficult
      to assess. It seems, however, that adequate Kt/V urea may be necessary for weight
      gain in underweight CAPD patients.

PMID- 11979353
TI  - Metabolic replacement of kidney function in uremic animals with a bioartificial
      kidney containing human cells.
AB  - Current renal substitution therapy with hemodialysis or hemofiltration has been
      an important life-sustaining technology, but it still has suboptimal clinical
      outcomes in patients with end-stage renal disease or acute renal failure. This
      therapy replaces the small solute clearance function of the glomerulus but does
      not replace the metabolic and endocrinologic functions of the tubular cells. This
      article shows that the combination of a synthetic hemofiltration cartridge and a
      renal tubule cell assist device (RAD) containing human cells in an extracorporeal
      circuit replaces filtration, metabolic, and endocrinologic functions in acutely
      uremic dogs. The RAD maintained excellent performance and durability
      characteristics for 24 hours of continuous use in the uremic animals. The RAD
      increased ammonia excretion, glutathione metabolism, and 1,25-dihydroxyvitamin D3
      production. Cardiovascular stability in the animals was documented in these
      studies during this extracorporeal treatment. With these results, clinical
      evaluation of this device in the treatment of severely ill patients with acute
      renal failure in an intensive care unit has been initiated.

PMID- 11979354
TI  - Reassessing the impact of cytomegalovirus infection in kidney and kidney-pancreas
      transplantation.
AB  - New antiviral agents and practice guidelines have been implemented to address
      cytomegalovirus (CMV) infection in organ transplantation. We hypothesized that
      such measures would reduce rates of symptomatic CMV infection, CMV disease, and
      CMV seroconversion and associated complications in renal transplant and
      simultaneous pancreas-kidney transplant recipients. We analyzed the impact of CMV
      in 1,424 renal transplant and simultaneous pancreas-kidney transplant recipients,
      transplanted at our center between January 1, 1994 and June 30, 1999. Most
      patients received quadruple sequential immunosuppression with high-dose acyclovir
      (800 mg four times daily) for 12 weeks as prophylaxis. High-risk patients (donor
      CMV-positive/recipient CMV-negative) received ganciclovir (500 to 1,000 mg three
      times daily) beginning in 1998, again for 12 weeks. One hundred and one renal
      transplant (9.0%) and 40 simultaneous pancreas-kidney transplant (13.4%)
      recipients experienced symptomatic CMV infection or CMV disease. Donor CMV
      positive/recipient CMV-negative patients had the greatest rates of CMV infection
      or CMV disease (25.2%; P = 0.0001 versus all other categories). The impact of CMV
      on outcomes was evaluated in a proportional hazards model. Symptomatic CMV
      infection or CMV disease increased the risk for subsequent rejection (relative
      risk, 2.11; P = 0.003) and non-CMV infection (relative risk, 2.24; P = 0.001). To
      determine if the effects of ganciclovir were masked by pre-1998 data, CMV
      infection and CMV disease rates for ganciclovir-treated patients (n = 62) were
      censored at 1 year and compared with acyclovir-treated patients (n = 287).
      Ganciclovir was associated with trends toward lower rates of infection and
      disease. It also delayed the time to infection or disease. Serologic testing in
      high-risk patients also showed late seroconversion, with 20% of patients
      seroconverting by 6 months, 12 weeks after the prophylaxis period. These data
      suggest that despite better prophylaxis strategies, CMV remains an important
      pathogen in renal transplant and simultaneous pancreas-kidney transplant
      recipients. This finding may require reassessment of prophylaxis strategies and
      the development of alternative or novel anti-CMV regimens.

PMID- 11979355
TI  - Pretransplant serum C-reactive protein and the risk of chronic allograft
      nephropathy in renal transplant recipients: a pilot case-control study.
AB  - Multiple factors contribute to the development of chronic allograft nephropathy
      (CAN) in renal transplant recipients, and atherogenesis is considered to be an
      important pathologic process contributing to the development of this disease.
      There is growing acknowledgment of the role of inflammation in the pathogenesis
      of atherosclerosis, and markers of inflammation, such as C-reactive protein
      (CRP), have been shown to predict atherosclerotic vascular disease in the general
      and end-stage renal disease populations. In this pilot study, we hypothesized
      that elevations in pretransplant concentrations of CRP predict an increased
      incidence of CAN after renal transplantation. This case-control study compared
      pretransplant CRP levels in patients with allograft dysfunction and biopsy-proven
      CAN (n = 15) with a control group of transplant recipients with normal allograft
      function (n = 43). The median concentration of serum CRP was significantly higher
      in the CAN versus the control patients (13.1 +/- 3.9 mg/L versus 3.5 +/- 2.5
      mg/L; P = 0.01). This difference was sustained when restricting to patients who
      did not experience acute rejection. When dividing the patients into tertiles
      based on CRP concentration, the adjusted risk of CAN increased more than
      threefold with each increment in CRP by tertile (adjusted odds ratio, 3.16; P =
      0.03). The findings of our pilot study show an association between pretransplant
      elevations of CRP and CAN in end-stage renal disease patients who go on to
      receive a renal transplant. Cohort studies in larger groups of transplant
      patients are needed to confirm a causal pathway between pretransplant
      inflammation, atherogenesis, and CAN.

PMID- 11979356
TI  - BK virus regulatory region rearrangements in brain and cerebrospinal fluid from a
      leukemia patient with tubulointerstitial nephritis and meningoencephalitis.
AB  - BK virus (BKV) was recovered by polymerase chain reaction (PCR) from brain,
      kidney, lung, urine, and cerebrospinal fluid (CSF) of a fatal case of BKV
      tubulointerstitial nephritis with dissemination to lung and brain. Viral
      regulatory regions in PCR-amplified urine and the lung samples were identical to
      the archetypal structure, WWT. In the brain and CSF, a rearranged sequence
      predominated, however. A 94-bp deletion preceded a 71-bp tandem duplication
      because the same 94-bp segment was deleted from both copies. PCR-amplified
      regulatory region products were cloned and sequenced to define further the extent
      of the rearranged structures. Two kidney clones were archetypal, whereas two
      others were rearranged differently from the brain and from each other. In
      contrast to the brain clones, the kidney rearrangements seemed to involve
      deletion after duplication. Three of four brain clones sequenced were identical
      to the rearrangement found to dominate in the PCR product. A fourth clone showed
      two short deletions without any duplication. The four CSF clones all showed
      rearrangements identical to that which was amplified by PCR from CSF and brain.
      This represents the first molecular analysis of a BKV strain obtained from a
      central nervous system infection, and it reveals regulatory region rearrangements
      reminiscent of those described in JC virus from brains with progressive
      multifocal leukoencephalopathy. We suggest that the presence in the CSF of BKV
      with a dominant rearranged regulatory region may be useful in the diagnosis of
      BKV meningoencephalitis secondary to BKV nephritis.

PMID- 11979357
TI  - Spontaneous and protracted partial remission of microscopic polyangiitis.
AB  - Microscopic polyangiitis (MPA), or microscopic polyarteritis, is an idiopathic
      small vessel vasculitis that frequently causes glomerular damage and renal
      failure and skin and lung damage in many cases. The renal lesions include focal
      necrotizing glomerulonephritis, extracapillary proliferative (crescentic)
      glomerulonephritis, and tubulointerstitial infiltration with polymorphonuclear
      leukocytes and lymphocytes. MPA often is associated with the presence of
      antineutrophil cytoplasmic autoantibody (ANCA) (myeloperoxidase positive) as a
      diagnostic marker. MPA commonly is regarded as a serious condition that places
      the survival of the kidneys and the patient at risk. Typically, there is a
      prodrome of some weeks to months, with rapid decline in renal function and
      dialysis as a potential outcome if intensive immunosuppressive treatment is not
      given or is delayed. We describe an otherwise typical case of MPA occurring in a
      52-year-old woman presenting with multisystem disease, antimyeloperoxidase ANCA
      antibodies, renal impairment, and necrotizing crescentic glomerulonephritis in
      whom this usual sequence of events was not followed because the patient refused
      steadfastly to have any treatment for nearly a decade. Renal function remained
      stable for nearly 10 years, although there were persistent proteinuria,
      microscopic hematuria, and antimyeloperoxidase ANCA antibodies. A late renal
      pulmonary relapse occurred, and immunosuppression was permitted only briefly.
      Prolonged renal and patient survival in the absence of immunosuppressive
      treatment has been reported rarely in this context.

PMID- 11979358
TI  - Nephrotic syndrome after treatment with pamidronate.

PMID- 11979360
TI  - Storage of full blood count samples causes a factitious increase in percentage of
      hypochromic cells.

PMID- 11979362
TI  - Use of base in the treatment of severe acidemia.

PMID- 11979364
TI  - 2001 Annual Report: ESRD Clinical Performance Measures Project.

PMID- 11979365
TI  - Endothelium in hepatic cavernous hemangiomas does not express the hyaluronan
      receptor for endocytosis.
AB  - The liver contains two distinct endothelial cell types: vascular and sinusoidal.
      Although cavernous hemangioma is the most common benign tumor of the liver,
      vascular or sinusoidal endothelial cell differentiation has not been described.
      An endocytic receptor responsible for the uptake and degradation of hyaluronan is
      present in the sinusoidal endothelium of the liver. The hyaluronan receptor for
      endocytosis (HARE) may therefore be a useful marker for sinusoidal endothelial
      cell differentiation. Using monoclonal antibodies specific for HARE, CD31, and
      factor VIII, we completed an immunohistochemical study of the endothelial cells
      of both hepatic cavernous hemangiomas and of nonneoplastic human liver. The anti
      HARE monoclonal antibodies showed diffuse strong staining of nonneoplastic liver
      sinusoidal endothelium. No staining of nonsinusoidal endothelium or the
      endothelial lining of the hemangiomas was seen with anti-HARE. In contrast,
      diffuse strong staining for factor VIII and CD31 was present in nonsinusoidal
      endothelium and cavernous hemangioma endothelium. Neither factor VIII nor CD31
      staining was present in the sinusoidal endothelium. In conclusion, the
      endothelium of hepatic cavernous hemangiomas demonstrates vascular but not
      sinusoidal differentiation based on the absence of HARE and presence of CD31 and
      factor VIII.

PMID- 11979366
TI  - Centrilobular histopathologic changes in liver transplant biopsies.
AB  - We evaluated centrilobular histologic changes seen on post-orthotopic liver
      transplantation (OLT) biopsies to refine the pathologic diagnosis by systematic
      study of morphologic and clinical data with possible identification of prognostic
      criteria. A total of 110 biopsies with zone 3 pathology from 59 patients were
      reviewed and correlated with clinical findings. Within the first 6 months post
      OLT (group I), 39 of 47 patients had combinations of centrilobular hepatocytic
      dropout, ballooning, and cholestasis on single or multiple biopsies attributed to
      perioperative ischemic/perfusion injury; 12 of 39 patients with all 3 features
      present had increased incidence of biliary complications and sepsis and decreased
      1-year patient and graft survival; 17 of 39 patients with 2 of the 3 features had
      increased biliary complications but not decreased 1-year survival; and the
      remaining 8 of 47 patients had central venulitis associated with acute cellular
      rejection. After 6 months post-OLT (group II), 14 patients, including 2 from
      group I, had biopsies with centrilobular pathology; 8 of 14 had central venulitis
      related to rejection (acute, 4; chronic, 4), and fibrosis was seen in 8
      (rejection, 6; cardiac problems, 2). In conclusion, combinations of centrilobular
      hepatocytic ballooning, dropout, and cholestasis are seen in association with
      reversible or irreversible ischemic/perfusion damage in the early post-OLT
      period. The presence of all 3 features is associated with a poor outcome. Central
      venulitis as a feature of acute/chronic rejection is seen at any time post-OLT
      and is not a predictor of poor graft/patient survival.

PMID- 11979367
TI  - Correlation of histology, viral load, and in situ viral detection in hepatic
      biopsies from patients with liver transplants secondary to hepatitis C infection.
AB  - The diagnosis of hepatitis C infection in the setting of liver transplantation in
      based on several variables, including histopathologic changes and the presence of
      viral RNA in the serum. It may be difficult to differentiate acute rejection from
      recurrent viral hepatitis in liver biopsies from patients who received liver
      transplants for end-stage hepatitis C infection. The purpose of this study was to
      analyzed the histologic features, viral load, and in situ viral detection in 37
      biopsies taken from 25 people who underwent liver transplant for end-stage
      hepatitis C infection. Hepatitis C antigen was detected in 9 of 37 (24%) biopsies
      using immunohistochemistry; the detection rate increased to 19 of 37 (51%) using
      reverse transcriptase in situ polymerase chain reaction for viral cDNA. Hepatitis
      E cDNA was detected in 4 of 37 (11%) cases, hepatitis G cDNA in 3 of 37 (8%)
      cases and in 1 case cytomegalovirus was noted; with several cases of dual
      infection, 22 of 37 (59%) of tissues were positive for at least 1 virus.
      Histologic parameters that significantly correlated with in situ viral detection
      included single-cell hepatocyte necrosis (P = 0.02), bile duct damage (P = 0.03),
      lymphoid aggregates (P = 0.02), and cholestasis (P = 0.01). Further, a serum
      viral load exceeding 1,250,000 viral equivalents/ml was strongly correlated with
      in situ viral detection in the liver (P = 0.01). We conclude that certain
      histologic features and an increased viral load are highly correlated with the in
      situ detection of viral RNA in the liver, which is consistent with recurrent
      viral infection.

PMID- 11979368
TI  - Utility of immunostaining for S-100 protein subunits in gonadal sex cord-stromal
      tumors, with emphasis on the large-cell calcifying Sertoli cell tumor of the
      testis.
AB  - This study concerns the immunohistochemical localization of S-100 alpha, S-100
      beta, and whole brain S-100 (wbS-100) in testicular large-cell calcifying Sertoli
      cell tumor (LCCSCT). We examined 8 LCCSCTs (7 benign and 1 malignant), 6 Sertoli
      cell tumors not otherwise specified (SCTs-NOS), 6 Leydig cell tumors (LCTs), 5
      ovarian Sertoli-Leydig cell tumors (SLCTs), and 7 gonadoblastomas (GBLs). The 8
      LCCSCTs showed immunoreactivity for S-100 alpha, S-100 beta, and wbS-100. Five of
      the 6 LCTs and the Leydig cell components in the ovarian SLCTs stained positively
      for S-100 alpha and wbS-100 but were negative for S-100 beta. SCTs-NOS and the
      Sertoli cell components in the SLCTs occasionally showed focal and weak/moderate
      positivity for S-100 alpha, S-100 beta, and wbS-100. Sex cord cells of the GBLs
      were positive for S-100 beta and wbS-100 and negative for S-100 alpha. Germ cell
      elements of the GBLs were negative for S-100 alpha, S-100 beta, and wbS-100. In
      nonneoplastic testicular parenchyma adjacent to the above-mentioned tumors, there
      was S-100 alpha reactivity in Leydig cells, rete testis, and a few Sertoli cells.
      S-100 beta reactivity was seen in a few Sertoli cells, Schwann cells, and some
      endothelial cells. WbS-100 reactivity was present in Leydig cells, a few Sertoli
      cells, rete testis, Schwann cells, and some endothelial cells. The results
      indicate that S-100 alpha and S-100 beta can potentially be used as
      immunohistochemical markers for LCCSCT, especially when differentiating it from
      LCT, which may mimic LCCSCT on routine histopathology. Although the biological
      significance of both S-100 subunits expression in LCCSCT remains unknown, these
      notable calcium-binding proteins may be associated with the characteristic
      calcification in LCCSCT through regulation of calcium levels in the tumor cells.

PMID- 11979369
TI  - Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of
      cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition.
AB  - Many cancers have altered expression of various cell adhesion molecules. One of
      these is CEACAM1, which has been found to be downregulated in several carcinomas,
      including prostate cancer. We explored its immunohistochemical expression in a
      set of 64 total prostatectomy specimens and compared it with that of the
      epithelial cell adhesion molecule E-cadherin and occludin, a tight junction
      associated molecule. The luminal surface of the epithelial cells of normal
      prostate glands and ducts showed a dense expression of CEACAM1. This pattern
      prevailed in prostate cancer of Gleason grades 1 to 3 as long as the cells
      maintained their polarity and formed individual glands. With "fusion" of glands
      (ie, in the transition to Gleason grade 4), the expression of CEACAM1 was lost in
      polygonal nonpolar cells and was lost or focally very weak in cells lining a
      lumen in the cribriform complexes. E-cadherin, which outlined the basolateral
      cell membranes of contacting neighboring epithelial cells was also downregulated
      in prostate carcinomas. However, the loss of E-cadherin expression in higher
      grades was gradual and not related to the Gleason 3 to >4 transition. Occludin
      was also lost in polygonal (ie, unpolarized) cells of Gleason grades 4 and 5, but
      remained expressed in all cells facing a lumen in all grades of cancer, which
      CEACAM1 was not. In conclusion, downregulation of CEACAM1 as well as that of
      occludin in prostate cancer is associated with loss of cell polarity. It
      coincides with the formation of the complex glandular architecture of Gleason
      grade 4 pattern or complete loss thereof in Gleason grade 5 patterns. The
      proliferative activity, measured as Ki67 labeling index, showed a fourfold
      increase in the carcinoma cells with lost CEACAM1 expression, supporting previous
      observations that CEACAM1 regulates cell proliferation. Immunohistochemical
      analysis of CEACAM1 expression patterns may be useful in assessment of the
      malignant potential of prostate carcinoma.

PMID- 11979370
TI  - Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein
      kinases in normal, hyperplastic, and carcinomatous human prostate.
AB  - This study investigate the expression of the mitogen-activated protein kinases
      (MAPKs) in normal prostate, benign prostatic hyperplasia (BPH), and prostatic
      cancer (PC), and also the possible relationship between the activity of these
      MAPKs and the apoptosis/proliferation index. Immunochemical techniques were
      carried out using 2 mouse monoclonal antibodies against human extracellular
      signal-regulated protein kinase (ERK) and Jun N-terminal kinase (JNK), and 1 goat
      polyclonal antibody against mouse p38. To compare the results obtained in the 3
      specimens, the average percentages of both epithelial and stromal immunostained
      cells were calculated on immunostained sections. For each of the 3 kinases
      studied, the percentage of immunostained stromal cells did not change with
      prostatic alterations. For both ERK and p38, the percentage of immunostained
      epithelial cells increased significantly in BPH and even more so in PC. For JNK,
      the percentage of immunostained epithelial cells increased significantly only in
      PC. These results suggest that ERK could be involved in the elevated
      proliferation indexes reported in BPH and PC, whereas p38 might contribute to the
      increased apoptotic index reported in PC. The most probable action of JNK in PC
      would be cell proliferation stimulation. Overexpression of MAPKs, involved in the
      development of prostatic hyperplasia and neoplasia, might be secondary to the
      overexpression of several growth factors.

PMID- 11979371
TI  - Inflammatory myofibroblastic tumors (inflammatory pseudotumors) of the
      gastrointestinal tract: how closely are they related to inflammatory fibroid
      polyps?
AB  - Inflammatory myofibroblastic tumors (inflammatory pseudotumors) and inflammatory
      fibroid polyps of the gastrointestinal tract both feature prominent inflammatory
      infiltrates admixed with spindle-shaped fibroblasts/myofibroblasts set in a
      collagenous, fibrovascular, or myxoid stroma. Erroneously, some have considered
      inflammatory fibroid polyps to be intraluminal manifestations of inflammatory
      myofibroblastic tumors. In this study, we have characterized the histopathology
      of inflammatory myofibroblastic tumors, tumors that have only rarely been
      reported in the gastrointestinal tract, and have focused on whether inflammatory
      myofibroblastic tumors and inflammatory fibroid polyps in the gastrointestinal
      tract are distinct or similar. Clinical, histopathologic, and immunohistochemical
      features of 38 inflammatory myofibroblastic tumors limited to the wall of the
      gastrointestinal tract were compared with those of 45 inflammatory fibroid
      polyps. Compared to patients with inflammatory fibroid polyps, those with
      inflammatory myofibroblastic tumors were younger (mean age 41 years vs. 53
      years); had larger tumors (mean 8 +/- 5.2 cm vs. 3.6 +/- 4.6 cm); presented with
      abdominal pain, fever, and weight loss more frequently and less frequently had
      bowel obstruction. Inflammatory fibroid polyps had more eosinophils and fibrosis
      and fewer lymphoid cell infiltrates than inflammatory myofibroblastic tumors. A
      regular vascular pattern was a feature of inflammatory fibroid polyps but not of
      inflammatory myofibroblastic tumors. Most (82%) inflammatory fibroid polyps were
      positive for CD34 versus none of the inflammatory myofibroblastic tumors. Smooth
      muscle actin was more frequently positive in inflammatory myofibroblastic tumors
      than in inflammatory fibroid polyps (86% versus 13%). Inflammatory
      myofibroblastic tumors were much less frequent and were more evenly distributed
      in the gastrointestinal tract than inflammatory fibroid polyps. Both appear to be
      benign processes. Inflammatory myofibroblastic tumors, but not inflammatory
      fibroid polyps, had a tendency to recur. In conclusion, inflammatory
      myofibroblastic tumors of the gastrointestinal tract are extremely rare and
      differ clinically, histologically, and immunohistochemically from inflammatory
      fibroid polyps.

PMID- 11979372
TI  - Biological and clinical significance of cytogenetic abnormalities in low-risk and
      high-risk gastrointestinal stromal tumors.
AB  - We report cytogenetic findings in 19 c-Kit-positive gastrointestinal stromal
      tumors (GISTs) that represent a heterogenous group of mesenchymal neoplasms with
      respect to site, histology, and biologic behavior. All of the GISTs (5 low-risk,
      11 high-risk, 3 recurrences) displayed clonal chromosomal aberrations; 15 were
      hypo- to near-diploid, and 4 were near-triploid and hypotetraploid. The most
      common abnormalities were loss of chromosomes 14 and/or 22, demonstrated in 14
      GISTs irrespective of site or predominant phenotype. Ten cases (2 low-risk, 5
      high-risk, 3 recurrences) were characterized by loss of both chromosomes 14 and
      22, 2 cases (1 low-risk, 1 high- risk), by loss of chromosome 14; and 2 high-risk
      cases, by loss of chromosome 22. Additional chromosomal aberrations occurred
      preferentially in high-risk and recurrent GISTs, including loss of 9p and 1p in 8
      cases each, loss of 15 in 6 cases, loss of 3p in 5 cases, loss of 13q and 10q in
      4 cases each, loss of 19 in 3 cases, and complete or partial gains of chromosomes
      5 and 4 in 2 cases each. More significantly, 5 of 6 patients with clinically
      aggressive GISTs, including 2 recurrences and 3 metastasing GISTs, were
      additionally characterized by loss of 9p; four of these had additional loss of
      chromosomes 1p and 15. The presented results herein indicate that loss of
      chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of
      site or differentiation, whereas malignant transformation and progression of
      GISTs appear to be associated with an increasing incidence of additional
      secondary aberrations.

PMID- 11979373
TI  - Different patterns of 11q allelic losses in digestive endocrine tumors.
AB  - Most foregut digestive endocrine neoplasms may be associated with the multiple
      endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never
      show such association. To investigate the pathogenetic involvement of the MEN-1
      gene and of putative additional oncosuppressor gene(s) distal to it, a
      comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to
      11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23
      midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at
      the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4
      MEN-1-associated PETs and was found to consistently and continuously span to the
      most distal marker investigated at 11qter. In contrast, only occasional,
      discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal
      (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and
      rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1
      region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via
      chromosomal breakage and complete loss of chromosome 11q; furthermore, these
      results expand beyond the 11q13 region the search for additional oncosuppressor
      gene(s) potentially involved in the genesis of these neoplasms. The low
      frequency, limited extension, and discontinuous distribution of 11q deletions in
      midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the
      pathogenesis of these tumors.

PMID- 11979374
TI  - CD69 expression correlates with expression of other markers of Th1 T cell
      differentiation in peripheral T cell lymphomas.
AB  - CD69, a marker of early T cell activation, is associated with Th1 T cell
      differentiation. Previously we found that peripheral T cell lymphomas could be
      subdivided based on the expression of markers of Th1 versus Th2 differentiation,
      including CXCR3, CD134/OX40, CCR4, and CD30. Here we report immunohistochemical
      staining for CD69 in frozen and paraffin sections of peripheral T cell lymphomas
      that exhibit immunoreactivity for markers of Th1 or Th2 differentiation. CD69
      expression correlated with immunoreactivity for other Th1 differentiation markers
      in 18 of 19 frozen specimens of peripheral T cell lymphomas (P = 0.0005). In 10
      of these cases in which paraffin-embedded tissue was available for study, CD69
      immunohistochemical staining of paraffin sections correlated with frozen section
      expression. CD69 immunostaining was performed on paraffin sections from 53
      additional cases of peripheral T cell lymphoma and correlated with
      immunoreactivity for other Th1 differentiation markers (P < 0.0001) and was
      associated with specific subtypes of peripheral T cell lymphoma, including
      angioimmunoblastic lymphoma, Lennert's lymphoma, and mycosis fungoides/Sezary
      syndrome, previously noted to express Th1 differentiation-associated markers.
      Anaplastic large cell lymphoma, both systemic and cutaneous, which typically
      exhibits immunoreactivity for markers of Th2 expression, was negative for CD69
      immunostaining in 22 of 24 cases. CD69 immunostaining results support previous
      findings that a subset of T cell lymphomas exhibits immunophenotypic features of
      either Th1 or Th2 T cell differentiation. In addition, CD69 is a useful
      immunohistochemical marker for specific T cell lymphomas in frozen and paraffin
      embedded tissue.

PMID- 11979375
TI  - Umbilical vein interleukin-6 levels correlate with the severity of placental
      inflammation and gestational age.
AB  - Interleukin-6 (IL6) and suppurating placental inflammation are markers of
      neonatal sepsis. The purpose of this study was to define a relationship between
      IL6 and acute chorioamnionitis and funisitis of the placenta, and to compare IL6
      levels in term and preterm neonates. Umbilical venous IL6 was measured in 137
      term and 110 preterm neonates. Acute chorioamnionitis was graded as none, mild,
      moderate, severe, and necrotizing. Funisitis was graded as none, 1 vessel, 2
      vessels, 3 vessels, or necrotizing. A 2-way analysis of variance with interaction
      was used to compare the IL6 levels. There was a stepwise progression of IL6
      levels with increasing severity of acute chorioamnionitis and funisitis. Term
      neonates showed an IL6 elevation with mild acute chorioamnionitis and single
      vessel vasculitis, which increased progressively until the inflammation became
      severe. In contrast, IL6 levels in preterm neonates did not increase
      significantly until severe acute chorioamnionitis or 3-vessel vasculitis was
      seen. Statistically significant differences in IL6 levels were seen in term
      versus preterm infants when the acute chorioamnionitis was mild or moderate or
      when the funisitis involved either 1 or 2 vessels (P < 0.05). The difference may
      be related to the relative immaturity of the preterm immune system, as has been
      demonstrated in vivo and in vitro. However, differences in management could be
      confounding factors. In conclusion, umbilical venous IL6 levels correlate with
      the severity of acute placental inflammation, with greater IL6 elevations in term
      infants compared to preterm infants until the inflammation becomes severe.

PMID- 11979376
TI  - Apoptosis and apoptosis-associated parameters in relation to tamoxifen exposure
      in postmenopausal endometrium.
AB  - Tamoxifen increases endometrial cell proliferation and the incidence of
      endometrial cancer in postmenopausal women. The purpose of this study was to
      evaluate apoptosis and apoptosis-related factors in endometrium in relation to
      tamoxifen exposure. We analyzed benign postmenopausal endometrium from breast
      cancer patients receiving tamoxifen (n = 35) and from controls (n = 24), and
      endometrial cancer tissue from tamoxifen-treated breast cancer patients (n = 15)
      and endometrial cancer from women without tamoxifen exposure (n = 51). Apoptosis
      was examined morphologically, and the percentage of apoptotic epithelial cells
      was defined as the apoptotic index. In the benign samples, the presence of
      apoptotic cells was also evaluated immunohistochemically by the expression of
      caspase-3 and the monoclonal antibody M30. The expression of Fas, FasL, and Bcl-2
      was analyzed in all tissue samples. No differences were observed in the mean
      apoptotic index in benign endometrium in tamoxifen users (0.17%) versus controls
      (0.08%), or in tamoxifen-exposed (2.46%) versus nonexposed endometrial cancer
      (2.28%). However, the ratio of the apoptotic index with the previously reported
      proliferation index was lower in benign endometrium from tamoxifen users than in
      controls (0.02 +/- 0.026 vs. 0.05 +/- 0.03, Mann-Whitney U <0.005). In benign
      endometrium FasL was more frequently expressed in tamoxifen-users than in
      controls (chi(2) <0.05). We conclude that the apoptosis/proliferation ratio in
      benign endometrium from tamoxifen users is lower than in controls, indicating
      that the tamoxifen-induced higher proliferation is not compensated for by
      increased apoptosis. An imbalance between cell proliferation and apoptosis, and
      possibly suppression of the antitumor immune response by FasL overexpression in
      tamoxifen-exposed endometrium might play a role in the development of endometrial
      cancer in tamoxifen users.

PMID- 11979377
TI  - Microsatellite instability, loss of heterozygosity, and loss of hMLH1 and hMSH2
      protein expression in endometrial carcinoma.
AB  - Microsatellite instability (MSI) due to replication errors occurs frequently in
      hereditary tumors. Association with functional inactivation of the mismatch
      repair (MMR) genes and lack of protein expression has been described. In
      endometrial carcinoma (EC), the prevalence and clinical significance of these
      phenomena are not well known. Therefore, DNA samples from 89 EC and 5
      metachronous tumors were analyzed with polymerase chain reaction, using 5
      microsatellite markers and a DNA sequencer for amplicon detection. The results
      were correlated with immunohistochemistry of hMLH1 and hMSH2. MSI at >or=2 loci
      (MSI-H) was detected in 10/89 EC (11%); 1 of 10 showed loss of both hMLH1 and
      hMSH2, and 5 of 10 showed loss of hMLH1 (P < 0.0001). MSI-H was observed
      frequently in tumors with mucinous differentiation (P = 0.048), >10% of solid
      cribriform pattern (P = 0.037), International Federation of Obstetrics and
      Gynecology (FIGO) stage III to IV (4 of 13; P = 0.016), and necrosis >5% (P =
      0.07). Loss of heterozygosity (LOH) in >or=1 loci was found in 17 of 156 (11%).
      Survival (Kaplan-Meier) was longer for patients with endometrioid tumors with
      predominant glandular pattern, <5% necrosis, low FIGO stage and grade,
      superficial myometrial infiltration, no lymph-vascular invasion (LVI), and loss
      of hMLH1 expression (all P <or= 0.04). Cox analysis showed independent value for
      stage, grade, histologic type and pattern, LVI, and hMLH1 expression (all P <
      0.05). Age, MSI status, LOH, peritumoral inflammatory reaction, hMSH2, and
      development of metachronous tumors did not influence survival. In conclusion, MSI
      phenotype was observed in a small subset of mainly advanced-stage EC, frequently
      showing mucinous differentiation, areas of solid-cribriform pattern, and
      necrosis. It is often associated with loss of hMLH1 expression, which may be a
      prognostic marker, but only rarely with defects of hMSH2.

PMID- 11979378
TI  - Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds.
AB  - It has been hypothesized that excessive activity of matrix metalloproteinases
      (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor
      healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin
      biopsies of standardized acute partial-thickness wounds in healthy volunteers (n
      = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of
      different etiologies (n = 34) by a combination of specific analyses of activity
      and protein localization. We also studied MMP-14 by immunohistochemistry and in
      situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742)
      endogenous activities differed significantly between acute and chronic wound
      tissues. Acute wound healing was characterized by induction of MMP-9 in the
      advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen
      in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was
      detected in wound edge keratinocytes. MMP-2 was increased and activated with
      acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial
      cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA
      or protein was detected solely in the stroma of both acute and chronic wounds. In
      conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased
      in chronic wounds compared to normally healing wound tissues. Chronic nonhealing
      wounds may not be caused by excessive gelatinase activity, but are distinguished
      from healing wounds by an unfavorable distribution and persistance of MMP-9.

PMID- 11979379
TI  - Implications of pathologist concordance for breast cancer assessments in
      mammography screening from age 40 years.
AB  - Three pathologists reviewed slides and reports of cancers arising in both the
      study and control populations of the U.K. trial of annual mammography screening
      from age 40 years. A total of 875 cases were scored independently as noninvasive,
      microinvasive, or invasive cancer, with the last also evaluated for histology
      grade, type, and lymphatic vascular invasion. Of these, 870 (99.2%) were
      confirmed malignant, 1 case had cytology only, and 5 were judged by all reviewers
      as benign. Reviewer complete concordance for the three classes of malignancy was
      achieved in 826 (95%) and majority agreement in 31 (3.6%) of 870 with complete
      data. All three readers recorded grade in 736 cancers, giving a kappa statistic
      of 0.69, 0.52, and 0.66 for grades I, II, and III, respectively, and 0.61
      overall. Agreement that the cancer was special type or not was obtained in 671
      (89.0%) with complete concordance in the nature of the type in 504 and majority
      view in 167; another 58 (7.7%) were characterised as "part special" pattern, with
      type disagreement in 23 (3%). The kappa statistic for single type subcategories
      in those cancers was substantial, at 0.68 overall. This improved to 0.76 for the
      last 230 invasive cancers after the pathologists agreed more explicit criteria
      for type discrimination. There was almost perfect agreement between original and
      review diagnosis of breast malignancy for both noninvasive/microinvasive and
      invasive cancer (kappa 0.84 and 0.91, respectively), justifying confidence in the
      diagnosis of breast cancer by U.K. pathologists. The specialists agreed
      substantially on qualitative histology features of type and grade of cancers, and
      improved further for typing by defining criteria. These consensus data, along
      with invasive size and node status, are reliable for use as surrogate measures of
      outcome, and to enhance interpretation of effect, when the trial case population
      sources are disclosed.

PMID- 11979380
TI  - Invasive papillary adenocarcinoma of the colon.
AB  - Colonic adenocarcinomas are among the most common type of tumors. In this report,
      we present the morphologic, immunohistochemical, and microsatellite findings of 2
      cases with a distinct invasive papillary component. Both tumors arose from polyps
      in middle-aged patients, followed an aggressive course, and showed a superficial
      adenomatous component. The immunohistochemical stains showed that the tumor cells
      were negative for p27 and p53; both tumors were microsatellite stable, that is,
      with no microsatellite instability in the 6 markers studied, and there was no
      loss of the mismatch repair proteins hMSH2 or hMLH1. These findings suggest that
      these tumors follow the tumor-suppressor pathway and represent an aggressive
      subtype of colonic adenocarcinoma.

PMID- 11979381
TI  - Loss of chromosome 22 and absence of NF2 gene mutation in a case of multiple
      meningiomas.
AB  - Multiple meningiomas are rare, and only 13 cases have been subjected to molecular
      genetic analysis to detect mutations of the tumor-suppressor gene
      neurofibromatosis type 2 (NF2) located on chromosome 22. Most of these cases
      display NF2 gene mutations parallel to loss of the chromosome 22 homolog,
      indicating that inactivation of this gene may represent an early event in the
      development of multiple meningiomas. We report a case of a 61-year-old woman who
      developed multiple (dorsal and intracranial) meningiomas. Cytogenetic and
      molecular genetic studies demonstrated the loss of a copy of chromosome 22 in the
      5 meningiomas studied and the absence of NF2 gene mutations in 4 of those
      available for this molecular analysis. These findings, together with similar data
      from 2 previously reported cases, suggest the participation of a tumor-suppressor
      gene other than NF2 on chromosome 22 in the pathogenesis of a subgroup of
      multiple meningiomas.

PMID- 11979382
TI  - Ultrasonographically assessed carotid atherosclerosis in Japanese type 2 diabetic
      patients: Role of nonesterified fatty acids.
AB  - The aim of the present study was to evaluate the association of carotid
      atherosclerosis (intimal-medial thickness [IMT] in plaque-free segments and
      carotid stenosis in plaque segments) with serum nonesterified fatty acids (NEFA)
      in diabetic and nondiabetic patients. Fifty-one nonobese nonhypertensive Japanese
      type 2 diabetic patients aged 38 to 83 years (60.0 +/- 1.5 years, mean +/- SEM)
      and 23 age-matched (60.4 +/- 2.2 years, P =.439; range, 36 to 74 years) and sex
      matched nondiabetic subjects were examined. The duration of diabetes was 9.6 +/-
      1.0 years. Body mass index (BMI), blood pressure (systolic pressure, diastolic
      pressure), glycosylated hemoglobin (HbA(1c)), and fasting concentrations of
      plasma glucose, serum lipids (triglycerides, total, and high-density lipoprotein
      [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) and serum NEFA were
      measured. Using high-resolution B-mode ultrasound scan, we measured IMT in plaque
      free segments of bilateral common carotid arteries, and the mean of IMT in 2
      vessels was used for the analysis. Furthermore, we calculated the degree of
      stenosis in plaque segments of bilateral common carotid arteries. The degree of
      carotid stenosis was expressed as a percentage ratio between the area of plaque
      and that of the lumen using the formula (Lumen Area - Residual Lumen) x 100. Both
      the areas were automatically measured by the system on a frozen transverse
      scanning plane at the site of maximal narrowing. When 2 or more plaques were
      present in the vessel, only that causing the greatest degree of stenosis was
      considered for analysis. Univariate regression analyses showed that mean IMT in
      plaque-free segments was positively correlated with age (r =.498, P =.0004) and
      NEFA (r =.354, P =.0188) in type 2 diabetic patients. The degree of stenosis was
      positively correlated to age (r =.422, P =.0028), duration of diabetes (r =.313,
      P =.0268) and NEFA (r =.540, P =.0003) in diabetic patients. Other variables,
      including BMI and lipid profile, were not associated both with mean IMT in plaque
      free segments and the degree of stenosis in plaque segments in our diabetic
      patients. Multiple regression analyses showed that mean IMT in plaque-free
      segments was independently associated with age (P =.0003, F = 15.2), which
      explained 26.1% of the variability of IMT in our diabetic patients. The degree of
      stenosis was independently predicted by NEFA (P =.0047, F = 8.9), which explained
      17.2% of the variability of the carotid stenosis in our diabetic patients. In
      contrast, mean IMT in plaque-free segments was positively correlated to age in
      nondiabetic subjects (r =.450, P =.0347). There was, however, no relationship
      between the degree of stenosis and the variables, including age and NEFA, in
      nondiabetic subjects. These results indicate that the factors contributing to IMT
      in plaque-free segments and the degree of carotid stenosis in plaque segments are
      different in nonobese nonhypertensive Japanese type 2 diabetic patients. IMT in
      plaque-free segments was independently associated with age both in nondiabetic
      and diabetic subjects, whereas the serum NEFA level independently predicted the
      degree of stenosis in plaque segments in our diabetic patients, while not in
      nondiabetic subjects. Thus, NEFA is considered to be one of the new risk factors
      responsible for the progression of carotid atherosclerosis in nonobese
      nonhypertensive Japanese type 2 diabetic patients.

PMID- 11979383
TI  - Relationship of regional adiposity to insulin resistance and serum triglyceride
      levels in nonobese Japanese type 2 diabetic patients.
AB  - The aim of this study was to investigate the relationships between insulin
      resistance and regional abdominal fat area, body mass index (BMI), and serum
      lipid profile in nonobese Japanese type 2 diabetic patients. A total of 63
      nonobese Japanese type 2 diabetic patients aged 45 to 83 years were examined. The
      duration of diabetes was 8.4 +/- 0.8 years. BMI, glycosylated hemoglobin
      (HbA(1c)) levels, and fasting concentrations of plasma glucose, serum lipids
      (total cholesterol, high-density lipoprotein [HDL] cholesterol, and
      triglycerides), and serum insulin were measured. The low-density lipoprotein
      (LDL) cholesterol level was calculated using the Friedewald formula (LDL
      cholesterol = total cholesterol - HDL cholesterol - 1/5 triglycerides). Insulin
      resistance was estimated by the homeostasis model assessment (HOMA-IR). Computed
      tomography (CT) was used to measure cross-sectional abdominal subcutaneous and
      visceral fat areas in all the patients. Adipose tissue areas were determined at
      the umbilical level. Subcutaneous and visceral abdominal fat areas were 136.5 +/-
      6.0 and 86.0 +/- 4.1 cm(2), respectively. Univariate regression analysis showed
      that insulin resistance was positively correlated with subcutaneous (r =.544, P
      <.001) and visceral (r =.408, P =.001) fat areas, BMI (r =.324, P =.009), HbA(1c)
      (r =.254, P =.001), serum triglycerides (r =.419, P <.001), and serum LDL
      cholesterol (r =.290, P =.019) levels and was negatively correlated with serum
      HDL cholesterol level (r =.254, P =.041). Multiple regression analyses showed
      that insulin resistance was independently predicted by the areas of subcutaneous
      (F = 6.76, P <.001) and visceral (F = 4.61, P <.001) abdominal fat and serum
      triglycerides (F = 8.88, P <.001) level, which explained 36.9% of the variability
      of insulin resistance. Moreover, the present study demonstrated that whereas BMI
      was positively correlated with visceral (r =.510, P <.001) and subcutaneous (r
      =.553, P <.001) fat areas, serum triglyceride level was positively associated
      with visceral (r =.302, P =.015), but not with subcutaneous (r =.222, P =.074)
      fat area. From these results, it can be suggested that (1) both subcutaneous and
      visceral abdominal fat areas are independently associated with insulin resistance
      and (2) visceral fat area, but not the subcutaneous one, is associated with serum
      triglyceride levels in our nonobese Japanese type 2 diabetic patients.

PMID- 11979384
TI  - Progressive defect of insulin action on glycogen synthase in obesity and
      diabetes.
AB  - The purpose of the present work was to have a closer view on the changes in the
      regulation of glycogen synthase (GS) activity by insulin in relationship with the
      impairment of nonoxidative glucose disposal in human obesity. Obese patients with
      normal glucose tolerance (12), impaired glucose tolerance (11), diabetes (10),
      and lean control subjects (15) participated to the study. A euglycemic,
      hyperinsulinemic clamp was performed and associated with indirect calorimetry.
      Muscle needle biopsies were taken before and at the end of the 2-hour clamp for
      measurements of glycogen synthase fractional velocity and total activity. Total
      GS activity was significantly decreased (P <.05), while its percent activation by
      insulin was still normal in the obese glucose-tolerant group, and nonoxidative
      glucose disposal was decreased by 56% (P <.001) and glucose oxidation still
      normal. Total GS activity was decreased by about 50% (P <.01) and GS was
      unresponsive to insulin in the glucose-intolerant and diabetic groups. In
      conclusion, our data show that insulin-stimulated nonoxidative glucose disposal
      and total glycogen synthase are very early defects observed in obese patients.

PMID- 11979385
TI  - Evaluation of assays available to measure free testosterone.
AB  - This study compared the results of various testosterone assays in a cross
      sectional study of 50 male subjects age 28 to 90 years. The purpose of the study
      was to determine the relationship of the various testosterone assays to one
      another. In addition, we determined week-to-week variability in testosterone and
      bioavailable testosterone in 16 subjects. The following assays were undertaken:
      total testosterone (T), free testosterone by equilibrium dialysis (FT(D)),
      bioavailable testosterone (BT), free testosterone by ultracentrifugation (FT(U)),
      and direct estimation of serum free T by an analog ligand radioimmunoassay
      (FT(A)). In addition, using total T and sex hormone-binding globulin (SHBG), we
      calculated the free androgen index (FAI = T/SHBG) and the free testosterone index
      (FTI) using the method of Vermeulen. In a second study, we measured the week-to
      week variation in T and BT in a group of older males. Lastly, we demonstrated
      excellent stability of serum stored at -70 degrees C for up to 7 years for T and
      BT. Correlations of the various assays to increasing age were significant for all
      assays except total T (r = -.126). The best correlation was found with BT (r = 
      .744, P <.001). All measures were statistically significantly correlated with FT.
      The best correlations were FTI (r =.807, P <.007) and BT (r =.670, P <.001). If T
      was used to classify hypogonadism in comparison to BT, it resulted in
      misclassification in 42% of cases. In addition, we demonstrated a marked week-to
      week variability in T and BT in older men with the T and BT being in the
      eugonadal range some weeks and hypogonadal on other occasions. This occurred in 8
      of 16 men for T and 10 of 16 men for BT. Based on these data, we suggest that the
      FTI or BT are the most practical methods to determine hypogonadism. There is a
      need for increased awareness that marked week-to-week variability within a single
      individual can occur for measurements of both T and BT.

PMID- 11979386
TI  - Apolipoprotein B and A-I distribution in Mexican urban adults: results of a
      nationwide survey.
AB  - The apolipoprotein (apo) B and A-I distribution found in a survey performed in
      417 Mexican cities is described. Information was obtained from 15,607 subjects
      aged 20 to 69 years. In this report, only samples obtained after a 9- to 12-hour
      fast were included (1,674 cases, 652 men and 1,022 women). The population is
      representative of the Mexican urban adults. Mean lipid concentrations were:
      cholesterol,182.7 mg/dL; triglycerides, 213 mg/dL; high-density lipoprotein (HDL)
      cholesterol, 38.3 mg/dL; and low-density lipoprotein (LDL) cholesterol, 116
      mg/dL. The mean concentration of apo B was 77.8 +/- 25.9 mg/dL and 71 +/- 22.8 in
      men and women, respectively. A continuous increase of apo B was observed as
      subjects got older. A tendency to decrease after age 60 was observed in men, but
      not in women. The body mass index (BMI) is a major determinant for the apo B
      concentrations. The 90th percentile of the apo B concentration identifies a
      similar proportion of abnormal subjects than the LDL cholesterol concentration of
      160 mg/dL. The 120 mg/dL concentration, upper normal limit level used in other
      populations, identified as abnormal only 3.8% of the cases. Regardless of the
      lipid abnormality, an apo B above the 90th percentile was associated with higher
      levels of glucose, cholesterol, triglycerides, and non-HDL cholesterol, despite a
      similar age and BMI. The overall mean concentration of apo A-I was 122.3 +/- 31
      mg/dL and 129 +/- 34 in men and women, respectively. In conclusion, our data show
      that the apo B and apo A-I concentrations in Mexican urban adults are lower
      compared with the levels reported in other ethnic groups. Previously used
      reference ranges are not useful in the population report herein. These
      observations strengthen the need for obtaining data in population-based studies
      worldwide.

PMID- 11979387
TI  - Protein-free diets do not protect high-incidence diabetes-prone BioBreeding rats
      from diabetes.
AB  - Dietary factors have been reported to affect the development of spontaneous
      diabetes in various colonies of inbred and outbred diabetes-prone (DP)
      BioBreeding (BB) rats. Several studies have attributed a protective effect to a
      diet omitting crude protein mixtures in favor of purified casein, hydrolyzed
      casein, or free amino acids. We have used inbred BB rats, all of which become
      diabetic in specific pathogen-free (SPF) conditions when fed ordinary rat chow,
      to test the capacity of 2 different protein-free diets to modulate BB rat
      diabetes in 2 distinct pathogen-free environments. BB rats known to all develop
      diabetes by 100 days of age were fed from birth with 1 of 3 diets. By 120 days of
      age, 100% of the animals on a standard diabetogenic chow diet, 83% of animals on
      an amino acid-based protein-free diet, and 100% of animals on a hydrolyzed casein
      based diet had developed diabetes (P >.05). A slight delay in the age of onset
      was observed among rats fed the amino acid-based diet, but this delay coincided
      with a reduction in weight gain among these animals compared with the rats on a
      standard diet. Histology showed insulitis in all rats at either diabetes onset or
      120 days of age. We conclude that our unique strain of specific pathogen-free BB
      rats are not protected from diabetes when fed an amino acid-based diet and
      suggest that their insensitivity to dietary manipulation may be due to an as yet
      unknown factor present in the diabetes-resistant (DR), but not the DP BB rat
      genetic background.

PMID- 11979388
TI  - Comparison of insulinotrophic actions of nateglinide with glibenclamide
      dissociated from absorption in conscious dogs.
AB  - Nateglinide is more rapidly absorbed than glibenclamide. Therefore, the different
      absorption kinetics of both drugs were eliminated by intraportal administration
      in conscious fasted dogs. The plasma insulin profiles were compared under similar
      kinetic changes in plasma drug concentrations. After a priming dose of
      nateglinide (1 mg/kg. 5 min) or glibenclamide (40 microg/kg. 5 min), plasma drug
      concentrations reached a peak at 4 minutes (nateglinide, 80 +/- 5 micromol/L, n =
      6 and glibenclamide, 263 +/- 60 nmol/L, n = 6) followed by a sustained level at
      approximately 30% of the peak concentration at 30 minutes. Nateglinide led to a
      rapid and constant reduction in arterial glucose of approximately 30% basal,
      while glibenclamide promoted a gradual decrease to approximately 50% basal at 120
      minutes. An increase in plasma insulin level by nateglinide of 4 times basal (218
      +/- 58 pmol/L v 47 +/- 3 pmol/L, P <.05, n = 6) occurred at 6 to 10 minutes
      followed by sustained release of 1.4 times basal (67 +/- 15 pmol/L, n = 6). The
      insulin surge was more than doubled (484 +/- 209 pmol/L, n = 6) under a
      euglycemic clamp. Insulin release by glibenclamide increased gradually reaching
      10-fold basal (449 +/- 166 pmol/L, n = 6) at 60 minutes. This was not enhanced
      during a euglycemic clamp. Lowering the primed doses of nateglinide resulted in a
      diminished peak plasma insulin concentration. In contrast, glibenclamide caused
      only a slower increase, but eventually reaching a similar peak. By increasing the
      continuous infusion of nateglinide, the sustained insulin release was not
      altered. Glibenclamide, but not nateglinide, evoked prompt and sustained insulin
      release in the continuing presence of the other. These results are consistent
      with the concept that nateglinide produces a quick, but very short-lived,
      interaction with sulfonylurea (SU)-receptors on plasma membrane by free access of
      the drug from the cell exterior. In contrast, glibenclamide promotes a slow and
      longer interaction with the receptor by distribution of the drug into the cell
      inferior. We conclude, therefore, that not only the different kinetics of
      gastrointestinal (GI) absorption, but also the inherent difference in the
      interaction with beta cells is attributed to the different insulin release
      characteristics between nateglinide and glibenclamide in vivo.

PMID- 11979389
TI  - Intact negative feedback of four cardiac hormones in congestive heart failure.
AB  - In 30 individuals with class III congestive heart failure (CHF), negative
      feedback of 4 cardiac peptide hormones, ie, long-acting natriuretic peptide
      (LANP), vessel dilator, kaliuretic peptide, and atrial natriuretic factor (ANF)
      from the same 126-amino acid (aa) prohormone were studied with the infusion of
      100 ng/kg body weight (BW) for 60 minutes of each of the 4 cardiac hormones and a
      saline control (n = 6 for each). LANP decreased the circulating concentrations of
      vessel dilator, kaliuretic peptide, and ANF by 24%, 55%, and 30%, respectively.
      Vessel dilator decreased the circulating concentrations of ANF, kaliuretic
      peptide, and LANP 27%, 12%, and 62%, respectively. Kaliuretic peptide decreased
      the circulating concentrations of LANP, ANF, and vessel dilator 89%, 67%, and
      70%, respectively. ANF decreased the circulating concentrations of LANP, vessel
      dilator, and kaliuretic peptide 88%, 59%, and 98%, respectively. Infusion of each
      of these 4 cardiac hormones decreased the excretion of the other 3 hormones into
      the urine by 11% to 92%. These results suggest that the respective cardiac
      hormones inhibit the release of each other rather than their breakdown, which
      would have increased their urinary concentrations. The feedback regulation of
      these hormones found previously in healthy humans is, thus, preserved in persons
      with CHF despite their increased endogenous circulating concentrations.

PMID- 11979390
TI  - Effects of chromium picolinate supplementation on insulin sensitivity, serum
      lipids, and body weight in dexamethasone-treated rats.
AB  - Chromium (Cr) is essential for the regulation of insulin action, and Cr
      supplementation has been studied as a potential therapy of insulin resistance and
      lipid abnormalities. Corticosteroid treatment is well known to cause the
      abnormality of carbohydrate metabolism. Recently, it has been reported that
      corticosteroid increases urinary loss of Cr, and Cr supplementation recovers
      steroid-induced diabetes mellitus. In this experiment, rats were treated daily
      with dexamethasone (DEX) (0.2 mg/kg, intraperitoneal [IP]) for the first 7 days
      and were further treated with DEX plus either chromium picolinate (CrP, 30
      mg/kg/d) orally or a placebo for a period of 14 days. At the end of experiment
      (D21), the control rats, which were treated only with DEX weighed 320 g (80% of
      initial weight) on average, but CrP-treated rats weighed 364 g (91% of initial
      weight. P <.05). Glucose tolerance tests (GTTs) and insulin sensitivity tests
      were conducted. During insulin sensitivity tests, the area under the curve (AUC(0
      ->120)) of the time-glucose concentrations curves in CrP-treated group were
      decreased compared with those in the control group (271.4 +/- 74.9 v 1,097.4 +/-
      722.2 mmol/L/min, P <.01). Fasting serum insulin levels in CrP-treated rats were
      clearly decreased by 46.9% compared with those in the control group (0.52 +/-
      0.19 v 0.98 +/- 0.36 nmol/L, P <.05). During the GTTs, the AUC(0-->120) for time
      glucose concentrations curves in CrP-treated group was not significantly
      different from the control group, but the AUC(0-->120) of serum insulin
      concentrations in the CrP-treated group were 55.8% lower than those in the
      control group (123.1 +/- 42.5 v 278.2 +/- 59.1 nmol/L/min, P <.01). The mean
      AUC(0-->120) of time-cholesterol concentration curves during GTTs did not
      significantly differ between the 2 groups (867.6 +/- 155.2 v 827.7 +/- 94.3
      mmol/L/h, P = not significant [NS]). In contrast, 1-hour and 2-hour plasma
      triglycerides were significantly lower in the CrP-treated group, and the mean AUC
      of the time-triglyceride curve was significantly lower in CrP-treated group than
      in the control group (3.4 +/- 0.5 v 5.9 +/- 1.3 mmol/L/h, P <.05). We suggest
      that Cr supplementation in DEX-treated rats can relatively reverse a catabolic
      state and increase insulin sensitivity. Our results support the hypothesis that
      Cr supplementation can be considered to improve carbohydrate and lipid metabolism
      in patients receiving corticosteroid treatment.

PMID- 11979391
TI  - Metabolic responses in a model of insulin resistance: comparison between oral
      glucose and meal tolerance tests.
AB  - The purpose of this investigation was to compare the benefits of a meal tolerance
      test (MTT) against those of an oral glucose tolerance test (OGTT) in one of the
      most commonly used models of insulin resistance, the Zucker fatty rat. Comparison
      of these two oral challenges will facilitate determination of the most effective
      means of inducing both glucose and insulin responses in this particular model and
      allow for possible therapeutic benefits to be examined more effectively. Eight
      week-old Zucker fatty rats (n = 7 or 8) were used to perform either an OGTT or a
      MTT following an overnight fast. The OGTT contained a final amount of
      carbohydrate (CHO) of 1.2 g/kg body weight (BW). The MTT (commercially available
      liquid meal), in addition to having fat and protein, included a final amount of
      available CHO and volume to match the OGTT. A saline-treated group served as
      control. A greater glucose excursion was observed following the OGTT compared to
      the MTT. The maximal change in glucose from baseline was 140 +/- 10 mg/dL (a 2.1
      fold rise) for the OGTT compared to 86.3 +/- 6.1 mg/dL (a 1.7-fold rise) for the
      MTT (P <.05). The MTT induced a greater change from baseline in insulin response
      compared to the OGTT (7.5 +/- 1.1 v 3.9 +/- 0.5 ng/mL, MTT v OGTT, respectively;
      P <.05). The saline challenge induced only minimal glucose and insulin responses
      in comparison to the other treatments. These results suggest that, in a model of
      insulin resistance, the MTT is a more potent insulin stimulator than glucose
      alone. A mixed meal, such as a MTT, provides a complete nutrient challenge (CHO,
      fat, and protein) that will induce both glucose and insulin responses, enabling a
      better capacity to detect differences in one of the most often used models of
      insulin resistance, the Zucker fatty rat.

PMID- 11979392
TI  - Enhancement of cholesteryl ester transfer in plasma by hormone-replacement
      therapy.
AB  - To study possible mechanisms for the suggested protective effect of hormone
      replacement therapy (HRT) with respect to cardiovascular disease we investigated
      lipoprotein parameters, mass and activity of lipoprotein-metabolizing enzymes,
      magnitude of postprandial lipemia, and vascular endothelial function in 13
      postmenopausal women. All patients were examined before and 3 months after
      implementation of HRT with estrogen alone (group A, n = 6) or estrogen plus
      gestagen (group B, n = 7). HRT (groups A and B) resulted in enhanced total
      transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to
      apolipoprotein B (apoB)-containing lipoproteins (56% +/- 11.45% v 50.82% +/-
      13.68%, P <.05) and increased apoA-I plasma concentration (171 +/- 30 v 147 +/-
      22 mg/dL, P <.05). Fasting triglycerides (TG) were increased (134 +/- 40 v 115 +/
      39 mg/dL, P <.05). In group A patients the magnitude of postprandial lipemia
      increased significantly (1,737 +/- 756 v 1,475 +/- 930 mg TG/dL plasma/8 h, P
      <.05) without any change in lipoprotein lipase (LPL) activity, but with a
      concomitant decrease in low-density lipoprotein (LDL) size. In both groups flow
      mediated dilation (FMD) reflecting vascular endothelial function was not
      influenced, suggesting that HRT may not directly affect vascular function but
      rather alters lipoprotein metabolism. The increase of apoA-I was not accompanied
      by an equivalent rise of HDL cholesterol. Based on the present data this finding
      can be readily explained by an increase in CE transfer from HDL to TG-rich
      lipoproteins, which is not due to increased cholesteryl ester transfer protein
      (CETP) plasma levels, but rather reflects an increase in fasting and postprandial
      TG. In conclusion, the net effect of accelerated CE transfer due to HRT depends
      on the balance of proatherogenic aspects, like the generation of small dense LDL,
      and antiatherogenic aspects, like the stimulation of reverse cholesterol
      transport.

PMID- 11979393
TI  - Sialic acid content in erythrocyte membranes from pregnant women affected by
      gestational diabetes.
AB  - Sialic acid (SA) content, membrane fluidity, and Na(+)/K(+)-adenosine
      triphosphatase (ATPase) activity were determined in erythrocyte membrane from 10
      nonpregnant women (HNPW), 16 pregnant women affected by gestational diabetes
      mellitus (GDM), and 25 healthy pregnant women (HPW). In GDM patients the membrane
      erythrocyte SA content was significantly increased compared with HNPW and
      membrane fluidity was significantly increased in comparison with HPW. Erythrocyte
      membrane Na(+)/K(+)-ATPase activity was significantly reduced in GDM patients
      compared both to HNPW and to HPW subjects. A significant inverse correlation was
      found between 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH)
      anisotropy and erythrocyte membrane SA content in HNPW and in HPW, while this
      significant correlation was not observed in GDM. The present results indicate
      that in comparison with normal pregnancy GDM is characterized by deep alterations
      of the erythrocyte plasma membrane physicochemical properties (increased
      fluidity) and functional activities (reduced Na(+)/K(+)-ATPase activity). These
      modifications might be at the basis of the altered blood viscosity and placental
      perfusion observed under such conditions. Moreover, these results show that in
      physiological pregnancy and in the nonpregnant state, the erythrocyte surface
      membrane fluidity is inversely correlated with SA content, while in GDM there is
      an unbalance of this relation, which might be associated with the
      microcirculatory abnormality present in this disease.

PMID- 11979394
TI  - Impaired vitamin E status in patients with parenchymal liver cirrhosis:
      relationships with lipoprotein compositional alterations, nutritional factors,
      and oxidative susceptibility of plasma.
AB  - Vitamin E is a lipid-soluble vitamin and an important antioxidant that protects
      lipoproteins and cell membranes from lipid peroxidation. The aims of the present
      study were to investigate, in patients with parenchymal liver cirrhosis, the
      following: (1) nutritional and vitamin E status in relation to compositional
      changes in lipoproteins; and (2) the effects of these alterations on the
      patients' plasma susceptibility to copper-mediated oxidation. Patients (n = 55)
      with liver cirrhosis and 25 healthy volunteers had vitamin E in serum and in
      isolated lipoprotein fractions analyzed by high-performance liquid chromatography
      (HPLC). Plasma susceptibility to peroxidation was measured by incubation with
      Cu(2+). Nutritional status was assessed by anthropometry. Vitamin E concentration
      was significantly decreased (P <.001) in the serum and in very-low-density
      lipoprotein (VLDL) and high-density lipoprotein (HDL) in cirrhotic patients. The
      decrease was related to the degree of liver impairment. There were significant
      correlations between cholesterol and vitamin E concentrations in serum and in all
      the lipoprotein fractions (r between 0.72 and 0.89; P <.001) in cirrhotic
      patients, but there were no significant relationships between vitamin E and any
      of the anthropometric indices of nutritional status. The plasma maximal oxidation
      rate was significantly increased in cirrhotic patients (P <.01) and was inversely
      related to the serum concentration of vitamin E (P <.05). We conclude that
      lipoprotein alterations and not nutritional factors should be regarded as major
      factors explaining serum vitamin E reduction in patients with parenchymal liver
      cirrhosis, and that vitamin E depletion is associated with an increased plasma
      susceptibility to oxidation.

PMID- 11979395
TI  - Preoperative growth hormone response to thyrotropin-releasing hormone and oral
      glucose tolerance test in acromegaly: a retrospective evaluation of 50 patients.
AB  - The objective of this study was to investigate the relationship between growth
      hormone (GH) dynamic tests (thyrotropin-releasing hormone [TRH] test and oral
      glucose tolerance test [OGTT]), insulin-like growth factor-I (IGF-I) plasma
      values, tumor size, and clinical outcome in patients with GH-secreting pituitary
      adenomas. Furthermore, we investigated the potential prognostic utility of the
      above biochemical parameters in the follow-up of patients with acromegaly. We
      studied 50 acromegalic patients (18 males and 32 females; mean age, 40 years;
      range, 16 to 69) who underwent trans-sphenoidal removal of a GH-secreting
      pituitary adenoma from 1990 to 1994. Preoperatively, we evaluated (1) GH
      plasmatic levels after an oral glucose load (OGTT) (blood samples were drawn at 
      15, 0, 30, 60, 90, 120, 150, and 180 minutes after oral administration of 0.75
      g/kg body weight [BW] of glucose), (2) GH plasma levels after a TRH test (200
      microg as an intravenous [IV] bolus), and (3) basal IGF-I plasma levels after an
      overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma
      values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT(3)),
      free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and urinary free
      cortisol. The same tests were performed every year for 5 years. All of the
      patients were classified into 4 subgroups according to the system of Hardy and
      Vezina. Preoperatively, "controlled" patients (n = 29) had a GH paradoxical
      response to TRH (n = 28) and an unresponsiveness to OGTT (n = 29); 23 of them
      belonged to the I and II classes. Only 5 poorly controlled patients (n = 21)
      showed a preoperative paradoxical response to TRH and 9 had a preoperative GH
      partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our
      data suggest that in the preoperative period in acromegalic patients the
      simultaneous presence of a GH paradoxical response to TRH and lack of GH
      inhibition after OGTT is inversely related to the tumor size and therefore more
      likely to be restored to normal by surgical treatment.

PMID- 11979396
TI  - Effects of treatment by laser-assisted uvuloplasty on sleep energy expenditure in
      obstructive sleep apnea patients.
AB  - The purpose of this study was to evaluate the effect of successful laser-assisted
      uvulopalatoplasty (LAUP) on sleep energy expenditure (EE) in obstructive sleep
      apnea syndrome (OSAS) patients. Fifteen healthy subjects (group I) and 25
      patients with moderately severe or severe OSAS (group II) proven by overnight
      sleep study and who wanted LAUP were enrolled. During the night of the sleep
      studies, EE was measured with a metabolic cart (indirect calorimetry with
      canopy), including basal metabolic rate (BMR), mean sleep EE, lowest sleep EE,
      ratios of mean sleep EE/BMR, and lowest sleep EE/BMR. For the OSAS patients, a
      second sleep study with EE measurement was performed 3 months after LAUP. Based
      on this assessment of their sleep architecture, they were divided into 2 groups:
      responders (group IIa) and nonresponders (group IIb). The mean sleep EE, the
      ratio of mean sleep EE/BMR and lowest EE/BMR were significantly higher in group
      II than group I. After LAUP in group II, 6 patients were found to be responders
      (group IIa) and 19 patients were nonresponders (group IIb). Group IIa had
      decreased mean sleep EE, ratios of mean sleep EE/BMR, and lowest sleeping EE/BMR
      after LAUP than before LAUP compared with no significant changes in group IIb
      after LAUP. In conclusion, there is increased sleep EE in moderately severe OSAS
      patients when compared with normal controls. LAUP, when effective in reversing
      the sleep abnormalities, also normalizes the sleep EE. If it does not adequately
      treat the OSAS, however, the sleep EE remains abnormal.

PMID- 11979397
TI  - Does enteral glutamine modulate whole-body leucine kinetics in hypercatabolic
      dogs in a fed state?
AB  - To determine whether enteral glutamine alters whole-body leucine metabolism in a
      state of hypercatabolism, 6 dogs adapted to a normocaloric, low-protein diet
      received intramuscular dexamethasone (0.44 mg. kg(-1). d(-1)) for 1 week, during
      2 separate study periods. On the last day of each period, intravenous infusions
      of L-[1-(13)C]leucine and L-[2-(15)N]glutamine were performed to assess whole
      body leucine and glutamine metabolism, and duodenal biopsies were obtained to
      determine gut protein fractional synthesis rate (FSR), while dogs were receiving
      enteral nutrition. The nutrient mixture supplied 6.2 kcal. h(-1) nonprotein
      energy per kg(0.75) of body weight (84% glucose, 16% fat) and 0.2 g amino acid
      per kg(-0.75). h(-1); the nutrient mixture was glutamine-free on the "control
      day," and supplemented with 1,150 micromol. kg(-1). h(-1) natural L-glutamine on
      the "glutamine day." Glutamine supplementation induced an approximately 56% rise
      in plasma glutamine appearance rate (P <.05), and was associated with an
      approximately 26% reduction in leucine oxidation (P <.05) with no change in
      leucine release from protein breakdown or nonoxidative leucine disposal, an index
      of whole-body protein synthesis. Glutamine supplementation improved net leucine
      balance (protein synthesis-protein breakdown) (-26 +/- 4 v -48 +/- 11 micromol.
      kg(-1). h(-1); P <.05). In addition, glutamine enhanced intestinal protein FSR by
      approximately 22% in the 4 dogs where it was assessed. We conclude that, in
      hypercatabolic adult dogs in the fed state, enteral glutamine supplementation
      acutely decreases leucine oxidation and improves net leucine balance, and may
      thus preserve body protein.

PMID- 11979398
TI  - The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in
      patients with type 1 diabetes.
AB  - Mealtime amylin replacement with the human amylin analog pramlintide as an
      adjunct to insulin therapy improves postprandial glycemia and long-term glycemic
      control in type 1 diabetes. Preclinical animal studies indicate that these
      complementary effects may result from at least 2 independent mechanisms: a
      slowing of nutrient delivery to the small intestine and a suppression of nutrient
      stimulated glucagon secretion. The former effect of pramlintide has previously
      been demonstrated in patients with type 1 diabetes. The present studies
      characterize the effect of pramlintide on postprandial glucagon secretion in this
      patient population. Plasma glucagon and glucose concentrations were measured
      before and after a standardized liquid meal in 2 separate randomized, double
      blind, placebo-controlled studies of pramlintide administration to patients with
      type 1 diabetes. In a 2-day crossover study, 18 patients received a 5-hour
      intravenous infusion of pramlintide (25 microg/h or 50 microg/h) or placebo in
      addition to subcutaneous (SC) insulin injections. In a 14-day parallel-group
      study, 84 patients received SC injections of 30, 100, or 300 microg of
      pramlintide or placebo 3 times daily in addition to SC injections of insulin. In
      both studies plasma glucagon concentrations increased in response to the meal in
      the placebo-plus-insulin group but not in any of the pramlintide-treated groups
      (all pramlintide treatment arms v placebo, P <.05). We conclude that mealtime
      amylin replacement with pramlintide prevents the abnormal meal-related rise in
      glucagonemia in insulin-treated patients with type 1 diabetes, an effect that
      likely contributes to its ability to improve postprandial glucose homeostasis and
      long-term glycemic control.

PMID- 11979399
TI  - Polymorphisms in exon 3 of the proopiomelanocortin gene in relation to serum
      leptin, salivary cortisol, and obesity in Swedish men.
AB  - The objective of the current study was to examine the potential impact of a
      cryptic trinucleotide repeat polymorphism in exon 3 of proopiomelanocortin (POMC)
      on serum leptin levels and salivary cortisol, as well as obesity and estimates of
      insulin, glucose, and lipid metabolism in 284 unrelated Swedish men born in 1944.
      Moreover, we examined if a single nucleotide polymorphism (SNP) (C-->T) in exon 3
      was associated with these characteristics. The amplification of the
      microsatellite locus yielded a 155-bp fragment and a fragment with one additional
      copy of the 9-bp repeat unit GGCAGCAGC (164 bp). The allelic frequencies were
      0.96 and 0.04, respectively. Tests for differences in phenotype showed that
      subjects with the longer polymerase chain reaction (PCR) repeat product (n = 21)
      had significantly higher serum leptin concentrations (P =.024) compared with
      subjects with the shorter PCR product (n = 230). Salivary cortisol levels, as
      well as obesity and its related metabolic perturbations, were the same across the
      POMC genotypes. In conclusion, a microsatellite polymorphism in exon 3 of POMC is
      associated with elevated serum leptin levels. This association might reflect
      variations in melanocortin expression and/or activity, because exon 3 contains,
      among others, the coding sequences for melanocortins.

PMID- 11979400
TI  - Lipid peroxidation and protein modification in a mouse model of chronic iron
      overload.
AB  - Iron-storage diseases are believed to cause organ damage through generation of
      reactive oxygen species. Using a murine model of iron overload, we found that
      hepatic iron stores increased logarithmically during 3 weeks of chronic
      intraperitoneal administration of iron dextran, while hepatic glutathione
      peroxidase activity declined linearly by approximately 50% during the same
      period. Plasma concentrations of aliphatic aldehydes increased by 2- to 3-fold,
      and plasma malondialdehyde (MDA) by 6-fold. Modification of total liver protein
      by products of lipid peroxidation, including MDA-lysine, 4-hydroxynonenal-lysine,
      and N(epsilon)-(carboxymethyl)lysine (CML), increased by approximately 3-fold,
      while levels of the protein oxidation marker, methionine sulfoxide (MetSO), were
      unchanged. Skin collagen was resistant to modification until the third week, when
      2- to 3-fold increases in both CML and MetSO were observed. Our results document
      that iron overload increases lipid peroxidation, with concomitant increases in
      reactive aldehydes in plasma and chemical modification of tissue proteins. CML
      was a sensitive indicator of hepatocellular oxidative stress, compared to MetSO,
      while extensive modification of extracellular skin collagen was not observed
      until the late stages of iron overload and oxidative stress. These observations
      provide direct evidence for the contribution of reactive oxygen species, lipid
      peroxidation, and reactive carbonyl intermediates to the pathogenesis of iron
      overload diseases.

PMID- 11979401
TI  - No changes in serum fat-soluble vitamin and carotenoid concentrations with the
      intake of plant sterol/stanol esters in the context of a controlled diet.
AB  - Spreads enriched with plant sterol and stanol esters have been shown to possess
      similar cholesterol-lowering properties; however, their comparative capacity to
      alter circulating levels of other fat-soluble compounds has not been fully
      assessed. To compare actions of sterol and stanol ester consumption on serum fat
      soluble vitamin and carotenoid concentrations, 15 hypercholesterolemic subjects
      were fed each of 3 fixed foods treatment diets over 21 days using a randomized
      crossover controlled design. Diets contained either (1) margarine (M), (2)
      margarine with sterol esters (MSE; 1.92 g/d), or (3) margarine with stanol esters
      (MSA; 1.76 g/d). No significant differences were found in initial or final serum
      fat-soluble vitamin and carotenoid concentrations among the 3 phases. Serum
      retinol and alpha- and gamma-tocopherol concentrations at baseline and endpoint
      and percentage changes relative to baseline for MSE and MSA were not
      significantly different from those of the M diet. After adjusting for total
      cholesterol reduction, no changes for alpha- and gamma-tocopherol were found.
      Serum vitamins D and K, lycopene, and lutein concentrations and percentage
      changes did not differ across diets. Serum concentrations at baseline and
      endpoint and percentage changes for alpha- and beta-cryptoxanthin and alpha- and
      gamma-carotene were not different among the diets, nor did serum alpha- and gamma
      carotene concentrations to total cholesterol ratios differ. Serum lutein, beta
      cryptoxanthin, and alpha-carotene concentrations increased over time. In
      conclusion, our results show no effect of consumption of esterified plant sterols
      or stanols on serum fat-soluble vitamin or carotenoid concentrations compared
      with a control diet.

PMID- 11979402
TI  - Glucoregulatory endocrine responses to intermittent exercise of different
      intensities: plasma changes in a pancreatic beta-cell peptide, amylin.
AB  - Amylin, a peptide hormone released from the beta cells of the pancreas and
      cosecreted with insulin, is reported to inhibit the release of postprandial
      glucagon and insulin and to modulate gastric emptying. Changes in insulin and
      glucagon are important for controlling blood glucose levels under conditions in
      which metabolic rate is elevated, such as during and following exercise. Amylin
      may participate in the regulation of blood glucose levels in response to
      exercise, although the role of amylin has not been investigated. The purpose of
      the study was to determine the effects of a progressive, intermittent exercise
      protocol on amylin concentrations and to compare its response to circulating
      levels of insulin, glucagon, cortisol, and glucose. Seven well-trained males
      completed an intermittent exercise trial on a treadmill at four progressive
      exercise intensities: 60%, 75%, 90%, and 100% of maximum oxygen consumption
      (.VO(2)max). Blood samples were collected before exercise, after each exercise
      intensity, and for 1 hour following the exercise protocol. Subjects also
      completed a control trial with no exercise. Amylin and insulin rose from baseline
      (5.79 +/-.78 pmol/L and 4.76 +/-.88 microIU/mL) to peak after 100% .VO(2)max
      (9.16 +/- 1.35 pmol/L and 14.37 +/- microIU/ml), respectively and remained
      elevated during much of recovery. Thus, a progressive intermittent exercise
      protocol of moderate to maximum exercise intensities stimulates increases in
      amylin levels in well-trained individuals in a similar fashion to that of
      insulin, whereas glucagon concentrations only increase after the greatest
      exercise intensity, then quickly decline. Future studies should examine the
      effects of higher amylin concentrations in exercise recovery on glucoregulation.

PMID- 11979403
TI  - C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor
      gamma expression in adipose tissue of familial combined hyperlipidemia patients.
AB  - This study aimed to assess the role of complement C3, hormone-sensitive lipase
      (HSL), and peroxisome proliferator-activated receptor gamma (PPARgamma) gene
      expression in familial combined hyperlipidemia (FCHL). mRNA expression of these 3
      determinants of adipose tissue fatty acid (FA) metabolism was quantified in
      subcutaneous adipose tissue of 41 Finnish FCHL patients and 14 normolipidemic
      control subjects. No difference in steady-state mRNA expression level of C3, HSL,
      or PPARgamma mRNA was detected between the FCHL patients and the control
      subjects. Adipose tissue C3 mRNA expression level correlated with the area under
      the curve (AUC) for glucose and for insulin in FCHL patients and control
      subjects. HSL mRNA level was positively correlated with waist-to-hip ratio in
      patients, whereas the correlation was negative in control subjects. A significant
      correlation was observed for PPARgamma with free FA (FFA)-AUC in the FCHL group,
      and an inverse correlation with serum triglycerides (TG) in the control subjects.
      Although no difference in adipose tissue gene expression of C3, HSL, or PPARgamma
      was observed between the FCHL patients and the control subjects, several
      significant correlations were observed between the mRNA levels and FCHL-related
      metabolic parameters. Thus, the genes of C3, HSL, and PPARgamma may exert a
      modifying effect on lipid and glucose metabolism in FCHL. However, defects in
      adipose tissue expression of these genes are not likely to play a primarily role
      in the pathogenesis of FCHL in Finnish FCHL families.

PMID- 11979405
TI  - Imaging modalities for acute abdominal pain.
AB  - The diagnosis of acute abdominal pain remains hinged on the performance of a
      careful history and physical exam. Five to ten million emergency department
      visits occur each year for acute abdominal pain, creating a need to achieve
      improved diagnostic accuracy in an expedient fashion. Technologies such as
      ultrasound, computed tomography, magnetic resonance imaging, and diagnostic
      laparoscopy are helping achieve this goal. Of these, computed tomography appears
      to be the work horse of diagnostic imaging in the setting of acute abdominal
      pain. In this review, we examine each of these modalities, discussing their
      strengths and weaknesses. As well, we have reproduced an excellent algorithmic
      approach published by Martin and Rossi that shows the reader some basic
      diagnostic strategies for the evaluation of acute abdominal pain.

PMID- 11979406
TI  - Diagnostic laparoscopy.
AB  - Diagnostic laparoscopy is a powerful tool in the surgeon's armamentarium when
      used appropriately. There is a low complication rate and high diagnostic
      sensitivity. In addition to conventional operating room procedures, this
      technique can be applied in a variety of other settings, often without general
      anesthesia. Many patients can be spared invasive nontherapeutic laparotomies
      particularly in the area of trauma and cancer diagnosis. The surgeon must become
      a superior visual anatomist in order to be able to take maximum advantage of this
      technique.

PMID- 11979407
TI  - Laparoscopic cholecystectomy for acute cholecystitis: technical considerations
      and outcome.
AB  - Laparoscopic cholecystectomy (LC) is the preferred method of treatment for
      patients with gallbladder disease in the elective setting. Despite being
      technically more difficult, LC performed during the early course of acute
      cholecystitis can be safe and cost-effective. The current review discusses the
      diagnostic and therapeutic strategies that may help promote the safe and
      successful laparoscopic treatment of patients with acute cholecystitis.

PMID- 11979408
TI  - Laparoscopic appendectomy: indications and controversies.
AB  - The introduction of laparoscopic appendectomy has been more controversial than
      that of laparoscopic cholecystectomy. Randomized trials have been performed, as
      well as meta-analysis, with equivocal results regarding effectiveness. The
      further expansion of the technique for interval appendectomy and in cases of
      complicated appendicitis has introduced new controversies and success stories. We
      hope to review the current application of laparoscopic appendectomy in adults
      based on the available literature and discuss some current controversies.

PMID- 11979409
TI  - Laparoscopic approach to small bowel obstruction.
AB  - Historically, laparotomy and open adhesiolysis have been the treatment of choice
      for patients requiring surgery with small bowel obstruction (SBO), although
      laparotomy itself is an independent risk factor for bowel obstruction.
      Laparoscopy is known to create fewer intra-abdominal adhesions than open
      laparotomy. The observation that many patients with SBO have isolated adhesive
      bands has led to the use of laparoscopy as primary treatment of SBO by some
      authors. Although the laparoscopic approach to SBO has been described, the
      outcomes and indications are not well established. We will review the available
      literature regarding the laparoscopic approach to SBO. Additionally, we will
      describe the technique and make recommendations regarding which patients may be
      best suited for a trial of laparoscopy for adhesiolysis.

PMID- 11979410
TI  - Laparoscopic management of the perforated viscus.
AB  - Perforation of a hollow viscus is an emergency which should prompt a rapid and
      effective treatment. Open surgery has been considered the standard approach, but
      the use of laparoscopy for diagnostic purposes and treatment in favorable
      circumstances and locations appears to be a safe alternative with a number of
      advantages. Indications and contraindications, which depend on the nature of the
      disease, the duration of the perforation and the location, are discussed in
      detail.

PMID- 11979411
TI  - Pancreatic necrosis: pathogenesis and endoscopic management.
AB  - This review outlines advances in our understanding of the pathogenesis of severe
      acute pancreatitis. It reviews the current general management of these patient
      and the various advances in the endoscopic treatment approaches for patients with
      infected pancreatic necrosis and those who do not improve on conservative
      management. The technique of laparoscopic infracolic pancreatic necrosectomy and
      irrigation of the lesser sac is described in detail.

PMID- 11979412
TI  - Laparoscopy in gynecologic emergencies.
AB  - Laparoscopy is ideal for the diagnosis of acute pelvic pain and the treatment of
      gynecologic emergencies. It is as safe and effective as laparotomy for the
      treatment of ectopic pregnancy, ovarian cysts, dermoid cysts, and adnexal
      torsion. Treatment with laparoscopy results in shorter hospital stay and faster
      recovery. Future fertility is not compromised and in some cases may be improved
      with laparoscopic treatment. There are also studies suggesting that laparoscopy
      can be used safely for the diagnosis and treatment of gynecologic emergencies in
      the first and second trimester of pregnancy.

PMID- 11979413
TI  - The epidemiology of gastric cancer.
AB  - The epidemiology of gastric cancer is remarkable for both its dramatic decline in
      incidence over the past century and its continuing presence as the second leading
      cause of cancer deaths worldwide despite this decline. Factors including
      increased consumption of fruits and vegetables, and decreased intake of salty
      foods have largely been credited for the decline. Epidemiologic studies continue
      to provide data on other gastric cancer risk factors, including associations with
      Helicobacter pylori infection, as well as dietary factors, tobacco, and alcohol
      intake. In response to the opposing trends of decreasing distal gastric cancer
      and increasing gastric cardia adenocarcinoma, studies are beginning to identify
      gastric cancer risk factors separately by tumor subsite. Future epidemiologic
      studies that include information on site of origin as well as molecular markers
      promise to yield more homogeneous classification of case groups, which will
      enhance identification of underlying disease processes.

PMID- 11979414
TI  - Molecular biology of gastric cancer.
AB  - Gastric cancer is one of the leading causes of cancer mortality in the world.
      Gastric adenocarcinomas account for more than 95% of gastric tumors, whereas
      gastrointestinal stromal tumors (GISTs) are the most common neoplasms of the rare
      gastric mesenchymal tumors. Although the incidence of mid-distal gastric
      adenocarcinomas is decreasing, the incidence of gastroesophageal junctional
      tumors and Barrett's adenocarcinomas is increasing for unknown reasons. The
      majority of gastric tumors are sporadic in nature. However, there are rare,
      inherited gastric cancer predisposition traits, such as germline p53 (Li-Fraumeni
      syndrome) as well as E-cadherin (CDH1) alterations in familial diffuse gastric
      cancers. Gastric cancer has been observed to be part of the spectrum of neoplasms
      associated with germline mismatch repair gene (MMR) alterations that give rise to
      the hereditary nonpolyposis colorectal cancer (HNPCC) entity. Comparative genomic
      hybridization analyses have identified several amplifications and losses of DNA
      copy numbers in gastric cancers. Loss of heterozygosity (LOH) studies have shown
      several chromosomal loci with significant allelic loss, thus indicating the
      possibility of harboring a tumor suppressor gene important in gastric
      tumorigenesis. Microsatellite instability (MIS) and associated alteration of the
      TGF-bIIR, IGFRII, BAX, E2F-4, hMSH3, and hMSH6 genes are found in a subset of
      gastric carcinomas. Cell adhesion molecule abnormalities such as those involving
      CDH1 may play an important role in diffuse-type gastric cancer development.
      Although, multiple somatic alterations have been described in gastric carcinomas
      at the molecular level, the significance of these changes in gastric
      tumorigenesis remains to be established in most instances. The critical molecular
      alterations in gastric cancers that may lead to advances in our armamentarium to
      combat this lethal disease remain to be fully characterized.

PMID- 11979415
TI  - Staging, stage migration, and patterns of spread in gastric cancer.
AB  - Background concerning tumor node metastasis (TNM) staging of gastric cancer is
      presented, with special attention to the issue of stage migration. Patterns of
      spread are also reviewed and current problems in local-regional control are
      emphasized.

PMID- 11979416
TI  - Gastric cancer--patterns of relapse after surgical resection.
AB  - A knowledge of patterns of relapse after initial treatment with surgery alone is
      essential to determining the relative importance of both local (irradiation) and
      systemic adjuvants (chemotherapy, other) to surgery. A presentation of anatomic
      factors and pathways of tumor spread provides a basis for understanding the
      subsequent patterns of relapse data found in clinical, autopsy, and reoperative
      series. Implications for adjuvant therapy are summarized.

PMID- 11979417
TI  - Surgical approaches and outcomes in the treatment of gastric cancer.
AB  - Resection with extended lymphadenectomy in obtaining local-regional control with
      negative margins remains the only potentially curative modality in the treatment
      of gastric cancer. Complete (R0) resections, along with depth of invasion and
      adequate nodal staging, remain the most important prognostic factors. Because
      current chemotherapy regimens have limited benefit in advanced disease, the
      effectiveness of local-regional modalities takes on greater significance. The
      extent of surgical resection varies with the size, depth, location of the primary
      tumor, and the stage of disease. Studying patterns of recurrent disease and
      elucidating the impact of positive margins have led to insights into the biology
      of the disease and the limitations of local-regional therapies. Considerable
      controversy surrounds the notion of what defines an adequate lymph node
      dissection (LND). The recommendation of routine extended (D2) lymphadenectomy
      (ELND) is difficult to justify based on available randomized studies, but ELND
      may benefit selected patients when performed by surgeons who can accomplish the
      dissection with acceptable morbidity/mortality rates. An extended LND results in
      improved staging, allowing standardization of prognostic factors and survival
      data worldwide. Patient selection remains critical, limiting the role of surgery
      in advanced disease and reserving aggressive surgical resection for patients with
      high curative potential.

PMID- 11979418
TI  - Results of radiation therapy in gastric cancer.
AB  - Radiation therapy has been used in the treatment of patients with gastric cancer
      in two clinical settings: definitive therapy for locally advanced, unresectable
      tumors and adjuvant therapy following surgery for high-risk disease. For patients
      with locally advanced, unresectable or subtotally resected gastric carcinoma,
      radiotherapeutic approaches with and without chemotherapy have been employed,
      because these tumors appear localized, without clinically detectable metastases.
      Combined treatment with radiation therapy and chemotherapy appears to prolong
      survival but rarely results in long-term cure. Although only a modest effect was
      seen on survival, importantly, these studies established the foundation of
      contemporary combined-modality therapy and have served to stimulate further
      clinical investigation in gastric cancer as well as other gastrointestinal
      disease sites. For patients undergoing resection and lymphadenectomy with
      curative intent, the development of local or regional failure is common,
      occurring in 40% to 65% of patients. Sites of local and regional failure
      following resection include the gastric/tumor bed in 20% to 55%, the anastomosis
      in 25% to 50%, and the regional nodes in 40% to 50% of patients. Intergroup Trial
      0116 (INT 0116), a phase III trial, has recently demonstrated that adjuvant
      radiation therapy with concurrent and maintenance 5-fluorouracil (5-FU) and
      leucovorin (LV) reduces local failure and improves survival. Adjuvant therapy is
      now routinely administered to patients undergoing resection of gastric cancer for
      high-risk disease. Ongoing trials are now investigating new systemic agents with
      radiation therapy to establish efficacy compared to 5-FU and LV, as well as
      evaluating neoadjuvant approaches prior to resection.

PMID- 11979419
TI  - Chemotherapy options for gastric cancer.
AB  - Most patients diagnosed with gastric cancer in the United States and the Western
      World will either present with advanced disease or have recurrence after surgery,
      requiring discussions of chemotherapy. The evolution of chemotherapy for gastric
      cancer has been mixed with excitement and disappointment. Multiple single-agent
      chemotherapies have been shown to be only modestly effective in advanced disease,
      and the search for the best combination of therapy has been difficult.
      Contemporary combination therapies for advanced gastric cancer, usually
      containing 5-fluorouracil (5-FU) and/or cisplatin, demonstrate response rates in
      the 20% to 40% range, with median survivals between 6 and 12 months. While newer,
      standard chemotherapeutics, including the taxanes and irinotecan, may offer
      modest additional benefits, each requires further examination in phase III
      trials. Among patients with curatively resected disease, postoperative
      chemoradiotherapy appears to improve overall survival significantly. As a greater
      understanding of the molecular basis of gastric cancer is gained, the inclusion
      of biologic-based therapies will hopefully advance our ability to treat patients
      with gastric cancer more effectively.

PMID- 11979420
TI  - Radiation treatment parameters in the adjuvant postoperative therapy of gastric
      cancer.
AB  - Radiation therapy will be used much more commonly in the treatment of
      adenocarcinoma of the stomach because of the results of the Intergroup Trial
      demonstrating an advantage to adjuvant postoperative chemoradiation therapy.
      Previous descriptions of radiation fields have not emphasized the variation in
      local spread patterns between tumors located in different portions of the stomach
      and the varying extent of the primary tumor and lymph node spread. Based on data
      obtained from surgical and pathologic series, we have recommended a variation in
      the radiation fields from those routinely applied at the present time. Tumors
      located primarily in the region of the gastric cardia have the highest risk of
      nodal involvement in the pericardial region and along the lesser and greater
      curvature, as well as risk of spread into the periesophageal tissue. However,
      there is a lower risk of involvement in the distally located nodes, especially in
      the gastric antrum, periduodenal, and porta hepatis regions. For a patient who
      has been well evaluated both surgically and pathologically, and found to be node
      negative, it may not be necessary to treat the nodes in these lower risk sites.
      Similarly, tumors that originate in the distal stomach, in the region of the
      gastric antrum, have a high likelihood of spread to the periduodenal,
      peripancreatic, and porta hepatis nodes, and a lower likelihood of spread to the
      nodes near the cardia of the stomach, the periesophageal and mediastinal nodes,
      or to the splenic hilar nodes. Any tumor originating in the stomach has a high
      propensity of spread to nodes along the greater and lesser curvature, although
      they are most likely to spread to those sites in close anatomic proximity to the
      primary tumor mass. Based on such information, we have described the nodal and
      primary sites that should be treated for different T- and N-stage tumors located
      in the cardia, body, or antrum of the stomach. These should be used as guides for
      defining appropriate field arrangements for the adjuvant postoperative therapy of
      gastric cancer.

PMID- 11979421
TI  - TCDD-mediated oxidative stress in male rat pups following perinatal exposure.
AB  - 2,3,7,8-tetrachlorododibenzo-p-dioxin (TCDD) is a highly persistent trace
      environmental contaminant and is one of the most potent toxicants known. Exposure
      to TCDD has been shown to cause oxidative stress in a variety of animal models.
      In this study, pregnant Long Evans rats were dosed with 1 microg TCDD/kg on
      gestational day (GD) 15 so as to investigate oxidative stress in the liver of
      male pups following gestational exposure to TCDD. Lipid peroxidation (TBARS),
      production of reactive oxygen species (ROS), and total glutathione (GSH) were
      assayed to identify changes in oxidative stress parameters in the pup liver at GD
      21 and postnatal days (PND) 4, 25, 32, 49, and 63. Mean ROS levels in pups were
      elevated at all time points tested with a significant elevation at PND 4 and PND
      25. However, pup hepatic lipid peroxidation was unchanged throughout the time
      course. In addition, hepatic total GSH levels were not significantly changed
      although the means for the TCDD-treated groups were less than those of the
      controls at all time points except PND 49. The results indicate that although the
      levels of ROS are increased following gestational/lactational exposure, this
      increase does not translate to direct oxidative damage or significant changes to
      endogenous antioxidant defense mechanisms. Further investigation into the effect
      of gestational/lactational exposure in pups should include additional endpoints
      for further characterization of the time course of the response, the effect upon
      extrahepatic tissues, and investigation of differences between male and female
      offspring.

PMID- 11979422
TI  - Chromium(VI) interaction with plant and animal mitochondrial bioenergetics: a
      comparative study.
AB  - The mechanism of Cr(VI)-induced toxicity in plants and animals has been assessed
      for mitochondrial bioenergetics and membrane damage in turnip root and rat liver
      mitochondria. By using succinate as the respiratory substrate, ADP/O and
      respiratory control ratio (RCR) were depressed as a function of Cr(VI)
      concentration. State 3 and uncoupled respiration were also depressed by Cr(VI).
      Rat mitochondria revealed a higher sensitivity to Cr(VI), as compared to turnip
      mitochondria. Rat mitochondrial state 4 respiration rate triplicated in contrast
      to negligible stimulation of turnip state 4 respiration. Chromium(VI) inhibited
      the activity of the NADH-ubiquinone oxidoreductase (complex I) from rat liver
      mitochondria and succinate-dehydrogenases (complex II) from plant and animal
      mitochondria. In rat liver mitochondria, complex I was more sensitive to Cr(VI)
      than complex II. The activity of cytochrome c oxidase (complex IV) was not
      sensitive to Cr(VI). Unique for plant mitochondria, exogenous NADH uncoupled
      respiration was unaffected by Cr(VI), indicating that the NADH dehydrogenase of
      the outer leaflet of the plant inner membrane, in addition to complexes III and
      IV, were insensitive to Cr(VI). The ATPase activity (complex V) was stimulated in
      rat liver mitochondria, but inhibited in turnip root mitochondria. In both,
      turnip and rat mitochondria, Cr(VI) depressed mitochondrial succinate-dependent
      transmembrane potential (Deltapsi) and phosphorylation efficiency, but it neither
      affected mitochondrial membrane permeabilization to protons (H+) nor induced
      membrane lipid peroxidation. However, Cr(VI) induced mitochondrial membrane
      permeabilization to K+, an effect that was more pronounced in turnip root than in
      rat liver mitochondria. In conclusion, Cr(VI)-induced perturbations of
      mitochondrial bioenergetics compromises energy-dependent biochemical processes
      and, therefore, may contribute to the basal mechanism underlying its toxic
      effects in plant and animal cells.

PMID- 11979423
TI  - Inhibition of acetylcholinesterase by physostigmine analogs: conformational
      mobility of cysteine loop due to the steric effect of the alkyl chain.
AB  - The effect of a series of physostigmine analogs on acetylcholinesterase activity
      was investigated. The second-order rate constant k(on) of the enzyme-inhibitor
      complex correlates with the conformational positioning of aromatic residues,
      especially Trp84, in the transition state complex. The van der Waals interactions
      are an important structural element of this conformational change. A transient
      mobility of the cysteine loop (Cys67-Cys94) was confined only to the presence of
      a significant steric effect. Even with this limitation, however, the steric
      effect seems to be an appropriate model for future tests on the "back door"
      hypothesis involving facilitated opening for faster product clearance.

PMID- 11979424
TI  - Correlation between the high expression of C/EBPbeta protein in F442A cells and
      their relative resistance to antiadipogenic action of TCDD in comparison to 3T3
      L1 cells.
AB  - We compared the ability of two clonally derived murine preadipocyte cell lines,
      3T3-L1(L1) and 3T3-F442A (F442A), to differentiate after treatment by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), and found that the former cell line was
      clearly suppressed by TCDD but the latter was not. It was initially postulated
      that the easiest way to explain the lack of response to TCDD in F442A cells could
      be an alteration in aryl hydrocarbon receptor (AhR) functionality. This
      hypothesis was tested first, but no differences were found in the levels or
      functions of AhR. To find an alternate explanation for such a differential effect
      of TCDD, we tested the action of several diagnostic agents on the process of
      adipocyte differentiation of these two cells. No differences were found between
      these two lines of cells in the susceptibility to the antiadipogenic action of 12
      0-tetradecanoylphorbol-13-acetate (TPA), or to TNFalpha, indicating that the
      basic biochemical components engaged in the antiadipogenic actions of these
      agents in these two cell lines are similar. In contrast, F442A cells were found
      to be more resistant to the antiadipogenic action of EGF or TGFbeta than L1 cells
      which were tested side by side. Based on the knowledge that TNFalpha
      preferentially affects C/EBPalpha and that TGFbeta specifically controls
      C/EBPbeta and delta in their antiadipogenic action, we hypothesized that the
      major cause for the differential response of these two similar cell lines could
      be the insensitivity of C/EBPbeta and/or delta of F442A cells to the action of
      TCDD. We could obtain supporting data for this hypothesis, showing that in F442A
      cells, the level of C/EBPbeta is already high even before the addition of
      adipocyte differentiation factors and that TCDD did not cause any significant
      changes in the titer of C/EBPbeta.

PMID- 11979425
TI  - Acute sodium arsenite administration induces pulmonary CYP1A1 mRNA, protein and
      activity in the rat.
AB  - Modulation of the cytochrome P450 (CYP) monooxygenase system (P450) by arsenite
      was investigated in male, adult Sprague-Dawley rats treated with a single dose
      (75 micromol/kg, sc) of sodium arsenite (As3+). Total CYP content and P450
      dependent 7-pentoxyresorufin O-pentylation (PROD) and 7-ethoxyresorufin O
      deethylation (EROD) activities of liver microsomes decreased maximally (33, 35,
      and 50% of control, respectively) 1 day after As3+ treatment. Maximum decreases
      of CYP content and P450 catalytic activities corresponded with maximum increases
      of microsomal heme oxygenase (HO) activity and with increased total plasma
      bilirubin concentrations. EROD activity increased maximally in lung (300%) 5 days
      after a single dose of As3+. Lung CYP1A1 mRNA and protein levels also increased
      maximally 5 days after treatment. A small but significant increase in EROD
      activity (65%) was observed in lung microsomes 24 h following a 1 h infusion of
      bilirubin (7.5 mg/kg) into rats. However, administration of bilirubin to the lung
      via intratracheal injection (0.25 and 2.5 mg/kg) did not increase CYP1A1
      monooxygenase activity or mRNA. This study demonstrates that P450 is modulated in
      an isozyme (CYP1A1 vs CYP2B1/2) selective manner in rat lung after acute As3+
      administration. Administration of bilirubin, a potential aryl hydrocarbon
      receptor (AHR) ligand, by infusion or intratracheal instillation did not
      upregulate pulmonary CYP1A1 at the mRNA level under our treatment conditions.

PMID- 11979426
TI  - Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6
      mouse in a tissue (kidney) selective manner.
AB  - Modulation of hepatic and extrahepatic detoxication enzymes Cyp1a1, Cyp2a5,
      glutathione S-transferse Ya (GSTYa) and NAD(P)H:quinone oxidoreductase (QOR)
      dependent catalytic activity and mRNA levels were investigated at 1, 2, or 4 days
      in liver, lung, or kidney of male, adult CD57 Bl/6 mice treated sc with a single
      dose (85 micromol/kg) of sodium arsenite (As3+). Maximum decreases of total
      hepatic cytochrome P450 (CYP) monooxygenase content and catalytic activities,
      occurring at 24 h, corresponded with maximum increases of heme oxygenase (HO-1)
      in all tissues, as well as maximum plasma total bilirubin. Extrahepatic increases
      in CYP were observed only in non-AHR dependent isozymes in the kidney, where both
      Cyp2a5 mRNA and catalytic activity increased maximally 24 h after treatment. In
      contrast, no significant changes in Cyp2b1/2-dependent PROD or mRNA activity and
      decreases in Cyp1a1-dependent-EROD activity were noted 1, 2, or 4 days after
      treatment. Increases in QOR catalytic activities were observed in all tissues
      examined with increased mRNA in kidney. On the other hand, GSTYa catalytic
      activity and mRNA increases were only detected in kidney. This study demonstrates
      the differential modulation of CYP, QOR, and GST-Ya, important drug metabolizing
      enzymes after acute As3+ administration. The induction of Cyp2a5, QOR, and GSTYa
      catalytic activity and gene expression occurred primarily in kidney during or
      shortly after conditions of oxidant stress.

PMID- 11979428
TI  - Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets.
AB  - Degradation of extracellular matrix is crucial for malignant tumour growth,
      invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a
      family of zinc-dependent neutral endopeptidases collectively capable of degrading
      essentially all matrix components. Elevated levels of distinct MMPs can be
      detected in tumour tissue or serum of patients with advanced cancer and their
      role as prognostic indicators in cancer is studied. In addition, therapeutic
      intervention of tumour growth and invasion based on inhibition of MMP activity is
      under intensive investigation and several MMP inhibitors are in clinical trials
      in cancer. In this review, we discuss the current view on the feasibility of MMPs
      as prognostic markers and as targets for therapeutic intervention in cancer.

PMID- 11979429
TI  - Clinical implications of serum C-reactive protein levels in malignant fibrous
      histiocytoma.
AB  - Paraneoplastic syndromes (PNSs) associated with mesenchymal tumors are uncommon.
      Previous reports sporadically described inflammatory PNSs with elevated serum C
      reactive protein (CRP) levels and leukocytosis in patients with inflammatory
      malignant fibrous histiocytoma (MFH) of soft tissue; however, the relationship
      between other subtypes of MFH and PNS has not been extensively investigated.
      Forty-six patients with primary MFH of soft tissues who underwent radical surgery
      were retrospectively analyzed. These patients were divided into 2 groups
      according to preoperative serum CRP level: normal (<1.0 mg/dl) and elevated (> or
      = 1.0 mg/dl). The correlation between serum CRP level and several
      clinicopathologic factors was analyzed. Correlation between preoperative serum
      CRP level and metastasis-free and overall survival was also investigated by
      univariate and multivariate analyses. Elevated preoperative serum CRP levels were
      found in 65% of patients with a mean of 3.7 mg/dl. There were statistically
      significant relationships regarding tumor size, depth, histologic subtypes,
      grade, stage and metastatic rate among normal and elevated CRP groups (p < 0.001,
      p < 0.02, p < 0.005, p < 0.001, p < 0.001 and p < 0.05, respectively). When the
      tumor was removed, the elevated CRP level subsided into the normal range and
      other abnormal laboratory findings diminished in all cases. In 11/14 relapsed
      cases that showed elevated CRP preoperatively, the serum CRP level re-elevated
      with tumor relapse. The normal CRP group showed significantly more favorable
      prognosis than the elevated CRP group in metastasis-free and overall survival on
      univariate analysis (p < 0.02, p < 0.05, respectively). Patients with MFH
      frequently present with an inflammatory PNS, such as elevated serum CRP level,
      which can be a useful marker of disease activity and a valuable prognostic
      indicator.

PMID- 11979430
TI  - Nicotine modulates the effects of retinoids on growth inhibition and RAR beta
      expression in lung cancer cells.
AB  - Epidemiological and animal studies have demonstrated that vitamin A and its
      natural and synthetic derivatives, retinoids, are effective agents in preventing
      the development of tobacco-associated cancers. Unfortunately, clinical trials of
      retinoids on cigarette smokers have shown lack of efficacy in preventing lung
      cancer. In our study, we investigated the effect of nicotine on the anti-cancer
      activity of all trans-retinoic acid (trans-RA) in human lung cancer cells. Our
      results demonstrated that nicotine could abrogate the growth inhibitory effect of
      trans-RA by suppressing its ability to induce the expression of RA receptor beta
      (RAR beta), a tumor suppressor. The inhibitory effect of nicotine was accompanied
      with induction of orphan receptor TR3. Inhibition of TR3 expression by
      overexpression of TR3 anti-sense RNA in H460 lung cancer cells strongly prevented
      the suppressive effect of nicotine on trans-RA activity. Treatment with nicotine
      or the cotransfection of TR3 expression vector inhibited the induction of RAR
      beta promoter activity by trans-RA in transient transfection assays. The
      inhibition of RAR beta promoter activity was due to the interaction of TR3 with
      orphan receptor COUP-TF, resulting in inhibition of COUP-TF DNA binding and
      transactivation on the RAR beta promoter. Furthermore, we found that nicotine
      failed to suppress the effect of a retinoid X receptor (RXR)-selective retinoid
      SR11237 on inducing both growth inhibition and RAR beta promoter activity, due to
      the ability of SR11237 to activate the RAR beta promoter through the RXR/TR3
      heterodimer. Together, our results demonstrate that nicotine suppresses the
      growth inhibitory effects of trans-RA by inhibiting RAR beta expression through
      its induction of TR3 expression and suggest that RXR-selective retinoids may be
      more effective than classical retinoids for preventing and treating tobacco
      associated cancers.

PMID- 11979431
TI  - Heparin-derived disaccharides modulate proliferation and Erb-B2-mediated signal
      transduction in colon cancer cell lines.
AB  - Organ-specific extracellular matrix (ECM) determines metastasis formation by
      regulating tumor cell proliferation. Hepatocyte-derived ECM enhances
      proliferation of colon cancer cell lines by increasing expression of tyrosine
      kinase receptors of the erb-B family. The active components in the ECM are the
      heparan sulfates, which are highly heterogeneous in their chemistry and size. We
      determined the effect of heparan sulfate disaccharides, of defined chemistry and
      present in high amounts in the liver heparan sulfate chains, on the proliferation
      of colon cancer cell lines and investigated the mechanism involved. The low
      metastatic cell line KM12 was stimulated to proliferate by a highly sulfated
      disaccharide, found in the highest amounts in hepatocyte-derived heparan sulfate.
      Growth of the highly metastatic cell line KM12SM was inhibited by the second most
      common disaccharide in hepatocyte-derived heparan sulfate. The effect of both
      disaccharides was not accompanied by changes in the expression of erb-B1, erb-B2,
      erb-B3 or heregulin-alpha. We determined whether the disaccharides modified the
      signal-transduction pathways mediated by the erb-B receptors. The erb-B2-specific
      tyrosine kinase inhibitor AG825 abolished the enhancement of KM12 cell
      proliferation by the stimulatory disaccharide. This disaccharide increased
      tyrosine phosphorylation of erb-B1 and erb-B2 receptors, effects that were
      abolished by AG825. Moreover, the disaccharide caused increased expression of
      cyclin D1 and of activated MAP kinase, again reduced in the presence of the
      inhibitor AG825. The growth-inhibitory disaccharide reduced phosphorylation of
      erb-B1, but not of erb-B2, receptors in KM12SM cells. In conclusion, not only
      hepatocyte-derived heparan sulfate but also disaccharide molecules derived from
      heparan sulfate can affect colon cancer cell proliferation. Their effect is
      mediated by modulation of the erb-B signal transduction.

PMID- 11979432
TI  - OVCA2 is downregulated and degraded during retinoid-induced apoptosis.
AB  - Retinoids, the natural and synthetic derivatives of vitamin A, have been shown to
      regulate the growth and differentiation of a wide variety of cell types and
      consequently have enormous potential as chemotherapeutic agents. We have
      previously identified 2 genes, termed OVCA1 and OVCA2, which are located in a
      small region showing a high frequency of allelic loss in breast and ovarian
      tumors and share a common exon. Recent studies have suggested that expression of
      OVCA1 may be influenced by retinoids. Therefore, we analyzed the expression of
      OVCA1 and OVCA2 in cells in response to treatment with all-trans retinoic acid
      (RA) and N-(4-hydroxyphenyl)retinamide (4HPR), or under conditions of low serum
      and confluence, to determine further the roles of OVCA1 and OVCA2 in cell growth,
      apoptosis and differentiation. We show that OVCA2 mRNA and protein are
      ubiquitously expressed and that they are downregulated in the lung cancer cell
      line Calu-6 after treatment with RA and 4HPR. In addition, we observed that OVCA2
      protein is proteolytically degraded in response to RA and 4HPR treatment in a
      time- and dose-dependent manner in the promyelocytic leukemia cell line HL60. In
      contrast, expression of the candidate tumor suppressor OVCA1 was not
      downregulated by these treatments. Furthermore, we demonstrate that OVCA2 is
      evolutionarily conserved and shows regional homology with dihydrofolate
      reductases (DHFRs), specifically with hydrolase folds found in alpha-beta
      hydrolases. Our results are in contrast to a previous report and show that OVCA2,
      not OVCA1 mRNA and protein, is downregulated in response to RA and 4HPR.

PMID- 11979433
TI  - Assessment of genomic instability in breast cancer and uveal melanoma by random
      amplified polymorphic DNA analysis.
AB  - Some types of cancer have been associated with abnormal DNA fingerprinting. We
      used random amplified polymorphic DNA (RAPD) to generate fingerprints that detect
      genomic alterations in human breast cancer. Primers were designed by choosing
      sequences involved in the development of DNA mutations. Seventeen primers in 44
      different combinations were used to screen a total of 6 breast cancer DNA/normal
      DNA pairs and 6 uveal melanoma DNA/normal DNA pairs. Forty-five percent of these
      combinations reliably detected quantitative differences in the breast cancer
      pairs, while only 18% of these combinations detected differences in the uveal
      melanoma pairs. Fourteen (32%) and 12 (27%) primers generated a smear or did not
      produce any band patterns in the first and second cases, respectively. Taking
      into account the ability of RAPD to screen the whole genome, our results suggest
      that the genomic damage in breast cancer is significantly higher than in uveal
      melanoma. Our study confirms other reports that the molecular karyotypes produced
      with random priming, called amplotypes, are very useful for assessing genomic
      damage in cancer.

PMID- 11979434
TI  - Testing mouse mammary tumor virus superantigen as adjuvant in cytotoxic T
      lymphocyte responses against a melanoma tumor antigen.
AB  - Cytotoxic T cells represent a powerful strategy for antitumor treatment.
      Depending on the route of injection, an important role for CD4 T cell-mediated
      help was observed in the induction of this response. For this reason, we
      investigated whether induction of a CTL response to the HLA-A2-restricted
      immunodominant peptide melanoma antigen Melan-A was improved by using rVVs
      expressing the CTL-defined epitope alone or in combination with an SAg. In the
      latter case, the few infected dendritic cells simultaneously presented an SAg and
      an antigen, i.e., peptide. Here, we show that the anti-Melan-A response was
      efficiently induced but not significantly improved by coexpression of the SAg.

PMID- 11979435
TI  - Constructing an adenocarcinoma vaccine: immunization of mice with synthetic KH-1
      nonasaccharide stimulates anti-KH-1 and anti-Le(y) antibodies.
AB  - There is mounting evidence to suggest that immunization-based strategies can be
      used to mobilize the human immune system against specific carbohydrate antigens
      displayed on the surface of cancer cells. Following isolation and identification,
      such antigens can be administered as conjugate vaccines. The tumor-associated
      carbohydrate antigen KH-1 is 1 such antigen and may serve as a potential target
      for immunization against adenocarcinoma. However, a serious impediment to the
      application of a vaccine-based approach involving this antigen is that its
      availability from natural sources is severely limited. In order to overcome this
      limitation, we have developed an efficient total synthesis of this complex
      glycolipid. We have extended our synthesis to reach a structurally related analog
      in which the ceramide portion of KH-1 is replaced with an allyl substituent.
      These synthetic advances have led to the preparation of 2 potential vaccine
      constructs, each based on the conjugation of the KH-1 nonasaccharide and the
      carrier protein keyhole limpet hemocyanin (KLH). In 1 construct (KH-1-Et-KLH),
      the nonasaccharide is conjugated to KLH via a simple ethyl linkage, while in the
      other (KH-1-MMCCH-KLH), conjugation is mediated by a 4-(4-N
      maleimidomethyl)cyclohexane-1-carboxyl hydrazide (MMCCH) cross-linker. We report
      here the immunological properties of these 2 constructs. Mice were immunized with
      either of the 2 KH-1-KLH vaccine candidates or the KH-1 ceramide, along with the
      immunological adjuvant QS-21. Immunization with the ceramide served as a negative
      control and, as expected, failed to stimulate the production of antibodies
      against the KH-1 glycolipid. The construct in which the KH-1 nonasaccharide is
      linked to KLH via a simple alkyl chain stimulated significant quantities of IgM
      antibodies, whereas the construct linked to KLH by MMCCH induced high titers of
      both IgM and IgG antibodies. Inhibition data demonstrated that antibodies
      generated in response to immunization with the KH-1-KLH constructs recognize not
      only the KH-1 antigen but also the Lewis(y) (Le(y)) antigen, which, from a
      structural perspective, is similar to the 4 residues located at the non-reducing
      end of the KH-1 nonasaccharide. Thus, the KH-1-KLH constructs elicit an immune
      response that successfully targets 2 adenocarcinoma markers. As assessed by FACS
      analysis, the antibodies raised were strongly reactive with the KH-1/Le(y)
      positive cell line MCF-7 but not with KH-1 and Le(y) negative melanoma cell
      lines. Based on the results of our study, a KH-1-KLH plus QS-21 vaccine is being
      prepared for clinical evaluation.

PMID- 11979436
TI  - Peripheral gamma delta T-cell deficit in nasopharyngeal carcinoma.
AB  - Previous studies identified CD56(+) and CD56(-) subsets of peripheral gamma delta
      T cells from healthy donors. Both subsets responded to stimulation by a myeloma
      cell line, XG-7 and undergo vigorous ex vivo expansion in the presence of
      exogenous IL-2. They are cytotoxic for different tumor targets including
      nasopharyngeal carcinoma, but they differ from one another in that the CD56(-)
      subset has an additional growth requirement for IL-7 and exhibited greater
      cytotoxicity against nasopharyngeal carcinoma (NPC) targets. These immune cells
      were further shown to retard tumor growth in a nude mice NPC model. To assess if
      these immune cells might contribute to host defense against NPC, we compared
      gamma delta T-cell status of NPC patients with healthy donors and survivors who
      had been in clinical remission of the cancer. It was found that peripheral gamma
      delta T cells of patients were impaired in their response to the stimulatory
      effects of XG-7 and exhibited weak or essentially no cytotoxicity for the NPC
      targets. The deficits were present in early and advanced stages of the cancer but
      were restored among survivors after successful treatment of the cancer. These
      findings support a role for peripheral gamma delta T cells in host defense
      against NPC. It was noted that these immune cells comprise less than 5% of
      peripheral blood monocytic cells and hence it was not surprising that this
      component of host defense was breached early in the development of the cancer.

PMID- 11979437
TI  - Cancer risks in first-generation immigrants to Sweden.
AB  - We used the nationwide Swedish Family-Cancer Database to analyse cancer risks in
      613,000 adult immigrants to Sweden. All the immigrants had become parents in
      Sweden and their median age at immigration was 24 years for men and 22 years for
      women. We calculated standardized incidence ratios (SIRs) and 95% confidence
      intervals (CIs) for 18 cancer sites using native Swedes as a reference. Data were
      also available from compatriot marriages. All cancer was decreased by 5% and 8%
      for immigrant men and women, respectively. However, most of the male increase was
      due to lung cancer for which male immigrants showed a 41% excess. Among
      individual cancer sites and immigrant countries, 110 comparisons were
      significant, 62 showing protection and 48 an increased risk. Most of the
      differences between the rates in immigrants and Swedes could be ascribed to the
      variation of cancer incidence in the indigenous populations. Some high immigrant
      SIRs were 5.05 (n = 6, 95% CI 1.82-11.06) for stomach cancer in Rumanian women
      and 2.41 (41, 1.73-3.27) for lung cancer in Dutch men. At some sites, such as
      testis, prostate, skin (melanoma), kidney, cervix and nervous system, the SIRs
      for immigrants were decreased; in some groups of immigrants SIRs were about 0.20.
      The highest rates for testicular cancer were noted for Danes and Chileans. Women
      from Yugoslavia and Turkey had an excess of thyroid tumours. All immigrant groups
      showed breast, endometrial and ovarian cancers at or below the Swedish level but
      the differences were no more than 2-fold.

PMID- 11979438
TI  - Cancer risks in second-generation immigrants to Sweden.
AB  - We used the nationwide Swedish Family-Cancer Database to analyze cancer risks in
      Sweden-born descendants of immigrants from European and North American countries.
      Our study included close to 600,000 0-66-year-old descendants of an immigrant
      father or mother. We calculated standardized incidence ratios (SIRs) and 95%
      confidence intervals (CIs) for 17 cancer sites using native Swedes as a
      reference. All cancer was marginally below the Swedish incidence in offspring of
      immigrant origin. Decreased SIRs were observed for breast cancer among Norwegian
      descendants, melanoma among descendants of Hungarian fathers and ovarian and
      bladder cancer among descendents of Finnish mothers, all consistent with the
      difference in cancer incidence between Swedes and the indigenous populations.
      Cervical cancer was increased in daughters of Danish men, whereas thyroid cancer
      and non-Hodgkin's lymphoma were in excess in offspring of parents of Yugoslav and
      Asian descent. Even these results agreed with the high incidence rates in parents
      compared to Swedes, except that for non-Hodgkin's lymphoma other explanations are
      needed; these may be related to immune malfunction. Comparison of the results
      between the first- and the second-generation immigrants suggest that the first 2
      decades of life are important in setting the pattern for cancer development in
      subsequent life. Birth in Sweden sets the Swedish pattern for cancer incidence,
      irrespective of the nationality of descent, while entering Sweden in the 20s is
      already too late to influence the environmentally imprinted program for the
      cancer destiny.

PMID- 11979439
TI  - Lifelong vegetarianism and risk of breast cancer: a population-based case-control
      study among South Asian migrant women living in England.
AB  - To investigate the role of lifelong vegetarianism on the aetiology of female
      breast cancer, we conducted a population-based case-control study among South
      Asian migrant women from the Indian subcontinent resident in England. A total of
      240 South Asian breast cancer cases were identified from 2 cancer registries
      during 1995-1999. For each case, 2 age-matched South Asian controls were randomly
      selected from the age-sex register of the case practice. Lifelong vegetarians had
      a slight reduction, although not statistically significant, in the odds of breast
      cancer relative to lifelong meat-eaters, which persisted after adjustment for
      socio-demographic and reproductive variables [odds ratio (OR)=0.77; 95%
      confidence interval (CI)=0.50-1.18]. Analysis by food group revealed no linear
      trend in the odds of breast cancer with increasing consumption of meat (p=0.10)
      but the odds were higher for women in the top 75%. In contrast, there were strong
      inverse trends in the odds of breast cancer with increasing intake of vegetables
      (p=0.005), pulses (p=0.007) and fibre [non-starch polysaccharides, NSP (p=0.02)],
      with women in the highest 25% of intake of these foods having about 50% of the
      odds of those in the lowest ones. Adjustment for intake of vegetables and pulses
      reverted the odds of breast cancer in lifelong vegetarians relative to lifelong
      meat-eaters (OR=1.04; 95% CI=0.65-1.68) and attenuated the quartile-specific
      estimates for meat intake, whereas the inverse trends in the odds of breast
      cancer with intake of vegetables and pulses remained after adjustment for type of
      diet or meat intake. These findings suggest that lifelong vegetarianism may be
      associated with a reduction in the risk of breast cancer through its association
      with a higher intake of vegetables and pulses. Although it is not possible to
      exclude the possibility that lifelong meat abstention may also play a role, the
      findings provide evidence that a diet rich in vegetables and pulses, such as
      those typically found in South Asian diets, may be protective against this
      cancer.

PMID- 11979440
TI  - Cigarette smoking and subsequent risk of lung cancer by histologic type in middle
      aged Japanese men and women: the JPHC study.
AB  - In order to update the findings of relative risk associated with cigarette
      smoking for lung cancer by histologic type in Japan, the data from a population
      based cohort study of 91,738 men and women were analyzed. During 1990-1999, 422
      lung cancer incident cases were identified. The relative risk for all incident
      cases associated with current smokers versus non-smokers was 4.5 [95% confidence
      interval (CI): 3.0-6.8] and 4.2 (95% CI: 2.4-7.2), for men and women,
      respectively. When divided by histologic type, relative risk for squamous cell
      carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7-34.7) and 17.5 (95% CI:
      4.9-62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6-4.9) and 2.0 (95% CI:
      0.8-5.0) for men and women, respectively. We confirmed that the lung cancer risk
      in men rose with increasing cigarette smoking, especially the duration of smoking
      among current smokers and decreased after the cessation of smoking among former
      smokers. Unlike the US or European countries, the relative risk did not increase
      in this updated study, compared with previous studies in 1960s to 1990s in Japan
      either for all incident cases or for specific histologic types and the magnitude
      of relative risks was substantially lower than that observed in the US or
      European countries, especially for adenocarcinoma.

PMID- 11979441
TI  - History of allergies and autoimmune diseases and risk of brain tumors in adults.
AB  - To explore a possible influence of the immune system in the development of brain
      tumors, we evaluated the relationship between history of allergies and autoimmune
      diseases and risk of brain tumors within a large, hospital-based case-control
      study. Cases (n = 782) were patients recently diagnosed with glioma (n = 489),
      meningioma (n = 197) or acoustic neuroma (n = 96) at hospitals in Boston, Phoenix
      and Pittsburgh (USA). Controls (n =799) were patients hospitalized for a variety
      of nonmalignant conditions and frequency-matched to cases by hospital, age, sex,
      race/ethnicity and distance of residence from hospital. Research nurses collected
      data by personal interview of patients. Odds ratios (OR) and 95% confidence
      intervals (CI) were calculated using unconditional logistic regression. There was
      a significant inverse association between glioma and history of any allergies (OR
      = 0.67, 95% CI = 0.52-0.86) or autoimmune diseases (OR = 0.49, 95% CI = 0.35
      0.69). No significant associations were evident for meningioma or acoustic
      neuroma with history of any allergies. An inverse association was observed
      between meningioma and history of autoimmune diseases (OR = 0.59, 95% CI = 0.38
      0.92). There was a suggestion of interaction between allergies and autoimmune
      diseases on risk of glioma (p = 0.06), with subjects having both conditions being
      at lowest risk (OR = 0.24, 95% CI = 0.14-0.42). Among the specific conditions,
      asthma and diabetes showed the most consistent associations (OR = 0.63, 95% CI =
      0.43-0.92 and OR = 0.44, 95% CI = 0.27-0.70, respectively). Our results add to
      evidence that persons with allergies or autoimmune diseases are at reduced risk
      of glioma. The basis of the associations is not clear, but they might imply a
      role of immunologic factors in the development of brain tumors. Published 2002
      Wiley-Liss, Inc.

PMID- 11979442
TI  - Environmental and heritable causes of cancer among 9.6 million individuals in the
      Swedish Family-Cancer Database.
AB  - The genetic and environmental components in 15 common cancers were estimated
      using the nationwide Swedish Family-Cancer Database. Tetrachoric correlations
      were used to describe similarity in cancer liability among family members.
      Structural equation modeling was used to derive estimates of the importance of
      genetic and environmental effects. Statistically significant estimates of
      proportion of cancer susceptibility, accounted for by genetic effects, were
      obtained for all studied cancers except for leukemia. The estimate was highest in
      thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%),
      breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%),
      rectum (12%), non-Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder
      (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental
      effects ranged from 0% (cervix) to 15% (stomach). The childhood shared
      environmental effects were most important in testicular cancer (17%), stomach
      cancer (13%) and cervix in situ (13%). Our results indicate that environment has
      a principal causative role in cancer at all studied sites except for thyroid. The
      relatively large effect of heritability in cancer at some sites, on the other
      hand, indicates that even though susceptibility genes have been described at many
      cancer sites, they are likely to explain only part of the genetic effects.

PMID- 11979443
TI  - Dietary risk factors for upper aerodigestive tract cancers.
AB  - We examined the association between whole-grain intake and incident upper
      aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer
      free women. We also studied established risk factors for upper aerodigestive
      cancers, including fruit and vegetable intake, smoking and alcohol intake. A
      mailed questionnaire at baseline in 1986 included a food-frequency questionnaire
      and assessment of other cancer risk factors. During the 14-year follow-up period,
      169 women developed cancer of the upper aerodigestive tract. For all upper
      aerodigestive cancers together, significant inverse associations were observed
      for the highest compared to the lowest tertile of whole grains [relative risk
      (RR) = 0.53, 95% confidence interval (CI) 0.34-0.81] and yellow/orange vegetables
      (RR = 0.58, 95% CI 0.39-0.87). In addition, those in the highest compared to
      lowest tertile of fiber intake from whole grain were less likely to develop upper
      aerodigestive tract cancer (RR = 0.56, 95% CI 0.37-0.84); fiber intake from
      refined grain was not significantly associated with upper aerodigestive tract
      cancer. Findings were generally similar for oropharyngeal (n = 53), laryngeal (n
      = 21), nasopharyngeal/salivary (n = 18), esophageal (n = 21) and gastric (n = 56)
      cancers, though numbers of cases were too small for statistical testing within
      individual cancers. These findings confirm previous observations that high intake
      of fruits and vegetables and that intake of whole grains and the fiber derived
      from them may reduce risk of upper aerodigestive tract cancers.

PMID- 11979444
TI  - Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene,
      droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1
      breast tumors in nude mice.
AB  - EM-652 exerts pure antiestrogenic activity in the mammary gland and endometrium,
      while tamoxifen, the antiestrogen most widely used for the treatment of breast
      cancer, exerts mixed antiestrogenic-estrogenic activity in these tissues. Our
      objective was to compare the agonistic and antagonistic effects of EM-652 with
      tamoxifen and 5 other antiestrogens on the growth of ZR-75-1 human breast
      xenografts in ovariectomized nude mice. During the 23 weeks of treatment at a
      daily oral dose of 50 microg, EM-652 was the only compound that decreased tumor
      size relative to pretreatment values, whereas the 6 other antiestrogens only
      decreased to various extents the progression rate stimulated by estrone. Under
      estrone stimulation, all groups of animals had more than 60% of their tumors in
      the progression category except for the EM-652-treated group, where only 7% of
      the tumors progressed. In the absence of estrone stimulation, progression was
      seen in 60%, 33%, 21% and 12% of tumors in the tamoxifen-, idoxifene-, toremifene
      and raloxifene-treated groups, respectively, while only 4% of tumors progressed
      in the EM-652-treated group. The agonistic and antagonistic actions of each
      antiestrogen were also measured on endometrial epithelial cell thickness. Our
      present findings indicate that EM-652, in addition to being the most potent
      antiestrogen on human breast tumor growth, has no agonistic effect in breast and
      endometrial tissues. Since previous data have shown benefits of EM-652 on bone
      density and lipid profile, this compound could be an ideal candidate for
      chemoprevention of breast and uterine cancers, while protecting against
      osteoporosis and cardiovascular disease.

PMID- 11979445
TI  - Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd
      bacteriopheophorbide leads to decreased metastases and increase of animal cure
      compared with surgery.
AB  - Photodynamic therapy (PDT), locally applied to solid C6 rat glioma tumors in the
      foot of CD1 nude mice, eradicated the primary tumor and also decreased the rate
      of groin and lung metastases. Pd-Bacteriopheophorbide (Pd-Bpheid), a novel
      photosensitizer synthesized in our laboratory, was used in our study. The primary
      lesion in the hind leg was treated by an i.v. injection of 5 mg/kg of Pd-Bpheid
      and immediate illumination (650-800 nm, 360 J/cm(2)). This protocol and the
      surgical amputation of the leg were compared for local and metastasis responses.
      Following PDT, hemorrhage, inflammation with tumor necrosis and flattening were
      observed and histologically verified in the photodynamically treated tumor.
      Whereas local tumor control rates were up to 64% following PDT, in surgically
      treated animals, local tumor control was absolute. The rates of metastases in the
      groin and the lungs were at least 12-fold lower in the photodynamically treated
      animals compared with untreated or surgery-treated groups. The overall cure rates
      after PDT or surgery were 36% and 6%, respectively, at 8 weeks. These findings
      suggest that local PDT with Pd-Bpheid, which acts primarily on the tumor
      vasculature, efficiently eradicates the solid C6 tumors. In addition, the local
      PDT of the primary lesion has beneficial therapeutic effects on remote C6
      metastasis, which is not obtained with surgery. It is therefore suggested, that
      although surgery is highly efficient for the immediate removal of the primary
      tumor, it lacks such systemic, therapeutic effects on distant metastases. Pd
      Bpheid-PDT may thus offer a potentially superior curative therapy for C6 glioma
      tumors in the limb by eradicating the target tumor and by reducing the rate of
      metastasis in the groin and lung, possibly due to innate immunity.

PMID- 11979446
TI  - Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice
      bearing colon 26/clone 20 adenocarcinoma.
AB  - We previously showed that the natural herb Coptidis rhizoma has an anticachectic
      effect in nude mice bearing human esophageal cancer cells. We further
      investigated this phenomenon by examining the anticachectic effect of C. rhizoma
      in syngeneic mice bearing colon 26/clone 20 carcinoma cells, which cause IL-6
      related cachexia after cell injection. We evaluated nutritional parameters such
      as serum glucose level and wasting of adipose tissue and muscle in tumor-bearing
      and non-tumor-bearing mice treated with C. rhizoma (CR) supplement or a normal
      diet. IL-6 levels in those mice were quantified by ELISA and real-time RT-PCR. CR
      supplementation significantly attenuated weight loss in tumor-bearing mice
      without changing food intake or tumor growth. Furthermore, these mice maintained
      good nutritional status. IL-6 mRNA levels in tumors and spleens and IL-6 protein
      levels in tumors and sera were significantly lower in tumor-bearing mice treated
      with CR supplement than in those treated with a normal diet. CR supplementation
      did not affect food intake, body weight, nutritional parameters and IL-6 levels
      in non-tumor-bearing mice. An in vitro study showed that C. rhizoma and its major
      component, berberine, inhibited IL-1-induced IL-6 mRNA expression in a dose
      dependent manner in colon 26/clone 20 cells. Our results showed that C. rhizoma
      exerts an anticachectic effect on colon 26/clone 20-transplanted mice and that
      its effect is associated with tumor IL-6 production. We also suggest that its
      effect might be due to berberine.

PMID- 11979447
TI  - Suberoylanilide hydroxamic acid (SAHA) overcomes multidrug resistance and induces
      cell death in P-glycoprotein-expressing cells.
AB  - Multidrug resistance (MDR) mediated by the ATP-dependent efflux protein P
      glycoprotein (P-gp) is a major obstacle to the successful treatment of many
      cancers. In addition to effluxing toxins, P-gp has been shown to protect tumor
      cells against caspase-dependent apoptosis mediated by Fas and tumor necrosis
      factor receptor (TNFR) ligation, serum starvation and ultraviolet (UV)
      irradiation. However, P-gp does not protect against caspase-independent cell
      death mediated by granzyme B or pore-forming proteins (perforin, pneumolysin and
      activated complement). We examined the effects of the chemotherapeutic hybrid
      polar compound suberoylanilide hydroxamic acid (SAHA) on P-gp-expressing MDR
      human tumor cell lines. In the CEM T-cell line, SAHA, a histone deacetylase
      inhibitor, induced equivalent death in P-gp-positive cells compared with P-gp
      negative cells. Cell death was marked by the caspase-independent release of
      cytochrome c, reactive oxygen species (ROS) production and Bid cleavage that was
      not affected by P-gp expression. However, consistent with our previous findings,
      SAHA-induced caspase activation was inhibited in P-gp-expressing cells. These
      data provide evidence that P-gp inhibits caspase activation after
      chemotherapeutic drug treatment and demonstrates that SAHA may be of value for
      the treatment of P-gp-expressing MDR cancers.

PMID- 11979448
TI  - Genetic analysis of RET, GFR alpha 1 and GDNF genes in Spanish families with
      multiple endocrine neoplasia type 2A.
AB  - Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific
      germline missense mutations in the RET proto-oncogene. This locus encodes a
      receptor tyrosine kinase whose activation requires the formation of a multimeric
      receptor complex including GDNF as a ligand and GFR alpha 1 as a coreceptor. In
      order to explore the role of RET, GFR alpha 1 and GDNF genes in the variation of
      phenotypes observed in MEN2A families, we analysed germline mutations of these
      genes in 4 unrelated Spanish MEN2A families (23 cases studied). We found 2 novel
      variants corresponding to a single change in position + 47 (intron 12) of RET and
      position +22 (intron 7) of GFR alpha 1. Furthermore, we observed strong co
      segregation between 2 polymorphisms of RET [G691S (exon 11) and S904S (TCC-TCG,
      exon 15) (100%, Fisher's exact test, p< 0.001)]. More interestingly, we found
      that these polymorphisms occurred at a significantly high frequency in patients
      with age at onset < 20 years old (Kruskal-Wallis's and Fisher's exact test, p =
      0.007). These findings suggest that the G691S and S904S variants of RET may
      somehow play a role on the age of onset of MEN 2A.

PMID- 11979449
TI  - Loss of heterozygosity analysis at the BRCA loci in tumor samples from patients
      with familial breast cancer.
AB  - The BRCA1 and BRCA2 genes are responsible for a high proportion of familial
      breast cancer; germline mutations in these genes confer a lifetime risk of about
      70% for developing breast cancer. Most of the described deleterious mutations are
      small deletions or insertions that originate a truncated protein; however, in
      many cases, they are amino acid changes whose significance is unknown. In these
      cases, there are some tests that can analyze the meaning of these variants, but
      most remain unclassified. The BRCA genes are tumor suppressors and it is believed
      that complete loss of the wild-type allele is a common mechanism of inactivation
      in tumors from patients carrying a germline deleterious mutation in these genes;
      if this is true, loss of heterozygosity (LOH) analysis in the tumor sample could
      help to distinguish if a rare variant is either a deleterious mutation or a
      common polymorphism. In the present study, we performed LOH analysis at the BRCA
      loci in 47 tumors from patients who belonged to high-risk breast cancer families
      and were carriers of any type of alteration in these genes. Our results suggest
      that (i) loss of the wild-type allele is the most common mechanism of
      inactivation in tumors from patients who carry a deleterious mutation in any of
      the genes, (ii) this loss is not common when we analyze familial tumors not
      associated with mutations in BRCA and (iii) LOH can be used to clarify variants
      of unknown significance in the BRCA genes.

PMID- 11979450
TI  - Expression of endoglin (CD105) in tumor blood vessels.

PMID- 11979453
TI  - Biology and treatment of familial hemophagocytic lymphohistiocytosis: importance
      of perforin in lymphocyte-mediated cytotoxicity and triggering of apoptosis.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is, without treatment, an
      invariably fatal disease of infancy and early childhood characterized by fever,
      hepatosplenomegaly, pancytopenia, and a widespread accumulation of T-lymphocytes
      and macrophages. During recent years, the diagnosis and the survival as well as
      the understanding of the disease have improved dramatically. Recent studies
      suggest that FHL is caused by impaired lymphocyte-mediated cytotoxicity and
      defective triggering of apoptosis, and that the symptoms are mediated by a pro
      inflammatory hypercytokinemia. Moreover, specific genetic alterations, mutations
      in the perforin gene, have been revealed in FHL patients. Perforin, which
      normally is secreted from cytotoxic T-lymphocytes and natural killer (NK) cells
      upon conjugation between effector and target cells, is able to insert into the
      membrane of the target cell. It there polymerizes to form a cell death-inducing
      pore through which toxic granzymes may enter the cell and trigger apoptosis. The
      establishment of perforin deficiency as a cause of the rapidly fatal disease FHL
      has demonstrated the essential role of perforin in human immune homeostasis.

PMID- 11979454
TI  - Antibody formation during intravenous and intramuscular therapy with Erwinia
      asparaginase.
AB  - BACKGROUND: Determination of the frequency of antibody formation during first and
      second exposure to Erwinia asparaginase after i.v. and i.m. administration.
      PROCEDURE: Thirty-nine children with newly diagnosed acute lymphoblastic leukemia
      (ALL) were included in this prospective study. Antibodies were determined (ELISA
      method) in plasma from these patients on specific days during and after therapy
      with 30,000 IU/m(2) i.v. or i.m. every day for ten days during the induction
      phase (first exposure). For 19 children, antibodies were measured in plasma
      during and after the re-induction phase (second exposure) following treatment
      with 30,000 IU/m(2) i.v. or i.m. twice a week for two weeks (Mondays and
      Thursdays). On the same days of therapy, enzyme activity (spectrophotometric
      method) and the concentration of asparagine (HPLC) was determined. RESULTS:
      During the first exposure, none of the patients developed anti-Erwinia
      asparaginase antibodies. During the second exposure, one patient (1 of 8
      patients) treated intravenously developed antibodies, which were associated with
      disappearance of enzyme activity and reappearance of asparagine. Three of eleven
      patients developed antibodies of pharmacokinetic importance after i.m. therapy.
      None of the children had any clinical symptoms of hypersensitivity. CONCLUSIONS:
      The formation of antibodies and subsequently altered pharmacokinetics of Erwinia
      asparaginase seemed to be of importance only during a second period of
      asparaginase therapy.

PMID- 11979455
TI  - Implications of cancer for school attendance and behavior.

PMID- 11979456
TI  - CNS late-effects after ALL therapy in childhood. Part III: neuropsychological
      performance in long-term survivors of childhood ALL: impairments of
      concentration, attention, and memory.
AB  - PURPOSE: To date, the event free survival (EFS) after treatment of childhood
      acute lymphoblastic leukemia (ALL) attains 80%. The survivor group is growing
      steadily. Therefore, the primary purpose of our study is to define the
      neuropsychological function and to describe which central nervous system (CNS)
      functions are impaired following the German ALL-BFM and COALL protocols for CNS
      negative patients. PATIENTS AND METHODS: In a cross-sectional multicenter study
      121 subjects, long-term survivors of childhood ALL in first continuous complete
      remission were investigated. Seven years ago, the subjects were treated as
      standard or medium risk patients according to ALL-BFM 81, ALL-BFM 83, or COALL 82
      protocols, receiving comparable treatments. According to different CNS
      prophylaxes, two subgroups were compared in the study: the non-cranially
      irradiated MTX-group (methotrexate-group) (n = 38) and the cranially irradiated
      RT-group (radiotherapy-group) (with MTX i.th.) (n = 83). Intellectual and
      cognitive abilities of these groups were evaluated using standardized
      psychometric techniques. The Kaufman factors Verbal Comprehension, Perceptual
      Organisation and Freedom from Distractibility were calculated. Demographical and
      clinical data collected at the time of the diagnosis were compared between both
      groups. The different prognoses for patients within both groups were taken into
      account using a defined risk factor. Analysis of variance was conducted to relate
      intellectual performance to age, gender, and CNS-treatment. RESULTS: The RT-group
      exhibited a lower Full Scale IQ than the MTX-group (101.2 +/- 15.9 vs. 109.9 +/-
      14.9, P = 0.031). Particularly for the Kaufman factor Freedom from
      Distractibility the RT-group showed the lower scores (96.9 +/- 14.1 vs. 105.5 +/-
      12.6, P = 0.037). Significant interactions between gender and CNS prophylactic
      treatment were observed for Full Scale IQ (P = 0.008), Verbal IQ (P = 0.012),
      Performance IQ (P = 0.024), Verbal Comprehension (P = 0.004), and Perceptual
      Organisation (P = 0.032). CONCLUSIONS: Cranial irradiation in combination with
      MTX therapy was associated with deficits in attention, concentration, and the
      ability of sequencing and processing, measured by the Kaufman factor Freedom from
      Distractibility. Our results support the strategy of avoiding prophylactic CNS
      irradiation in low risk patients.

PMID- 11979457
TI  - Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia:
      multi-institutional collaborative study.
AB  - BACKGROUND: In adults, it has been shown that the pharmacokinetics of doxorubicin
      are highly variable, despite standardization of the dose based on body surface
      area (BSA). The purpose of this study was to determine the plasma concentrations
      of doxorubicin and its active metabolite doxorubicinol in children treated for
      acute lymphoblastic leukemia (ALL). PROCEDURE: Children, 107 in number, aged 1.3
      17.3 years, were studied at Day 1 of induction therapy according to the current
      Nordic protocol. Five infants, 3-9 months old, were also included. Plasma samples
      were drawn 23 hr after the start of a 24-hr infusion of doxorubicin 40 mg/m(2),
      and analyzed by reversed-phase liquid chromatography. RESULTS: There was a more
      than 10-fold difference between patients in dose normalized plasma concentration
      of doxorubicin, median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin
      concentrations differed significantly between age groups (P = 0.003). Children
      aged 4-6 years had the highest doxorubicin concentrations, median 77.9 ng/ml,
      followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and older
      children had median values of about 50 ng/ml. Patients with white blood cell
      (WBC) count > 50 x 10(9)/L at diagnosis had significantly lower doxorubicin
      concentrations, median 55.3 ng/ml, than those with WBC count < 10 x 10(9)/L,
      median 64.4 ng/ml (P = 0.015). There was no difference in doxorubicin
      concentration between boys and girls. No correlation was found between
      doxorubicin levels and serum aminotransferases or serum creatinine. The
      concentration of doxorubicinol was 13% (median value) of that of doxorubicin.
      Four infants, 7-9 months old, had plasma clearance between 350-431 ml/min/m(2),
      which is in the same range as in older children. A 3-month-old infant had a
      clearance of 181 ml/min/m(2). CONCLUSIONS: The age groups who had the highest
      doxorubicin concentrations, (2-) 4-6-year-old children, are known to make up a
      large proportion of standard risk ALL cases with good prognosis. The correlation
      between doxorubicin plasma levels and clinical effect needs further study. The
      influence of age, body composition, and tumor burden on the pharmacokinetics of
      antineoplastic drugs should also be further explored, aiming at improvements in
      the current dosing regimen based on BSA.

PMID- 11979458
TI  - Epidemiologic studies in a population-based childhood cancer registry in
      Northeast Hungary.
AB  - BACKGROUND: Reports on the patterns of childhood cancer incidence are rare in
      Eastern Europe. To compare incidence rates and trends with international data, we
      processed records of the regional childhood cancer registry of Northeast Hungary.
      PROCEDURE: Our computerized database contains population-based information on
      childhood cancer cases (<15 years) diagnosed in residents of two counties of
      Hungary: leukaemias from 1973, non-CNS solid tumours from 1978, and CNS tumours
      from 1984. After a retrospective evaluation of completeness of ascertainment,
      descriptive epidemiologic analyses were performed for the years of operation of
      the registry. Age-standardized annual incidence rates and age-specific incidences
      were calculated. Trends were evaluated in linear regression analysis. RESULTS:
      The distribution of major histologic groups was similar to those observed in the
      Western countries with the exception that central nervous system tumours account
      for a higher percentage (27.3%). Average age-standardized annual incidence rates
      were as follows: all types of cancer: 120.7 per million; leukaemia: 37.3; CNS
      tumours: 31.6; lymphomas: 12.2; sympathetic nervous system tumours: 12.5; kidney
      tumours: 8.8. Significant increases were observed in incidence of leukaemia
      (average annual percent change AAPC: 0.7%), acute lymphoblastic leukaemia (AAPC:
      1.9%), and all cancer groups (AAPC: 2.6%), but not in acute non-lymphocytic
      leukaemia or in CNS tumours. The strongest increases in cancer incidence were
      detected in the age group of 10-14 years (AAPC: 4.4%) and in infants (AAPC:
      12.9%). CONCLUSIONS: Incidences and trends are in accordance with the data in the
      latest literature, however, the contribution of CNS tumours and the rate of
      increase in total cancer incidence proved to be higher. Further detailed genetic
      and environmental studies of cancer registries may shed light on the etiology of
      the observed differences whether they represent a pattern specific for this
      region.

PMID- 11979459
TI  - Epstein Barr virus associated pediatric nasopharyngeal carcinoma: its correlation
      with p53 and bcl-2 expression.
AB  - BACKGROUND: Pediatric nasopharyngeal carcinoma (NPC) is relatively rare. The
      Epstein Barr virus (EBV) association with the oncogenesis of NPC is well
      established. Apoptosis-related proteins, p53 and bcl-2, have also been described
      in adult NPC pathogenesis. PROCEDURE: From 1988 to 1998, 16 patients with NPC
      were treated at R. Gutierrez Children's Hospital and the National J.P. Garrahan
      Pediatric Hospital. Their median age was 12 years (range 8-20), 2 females and 14
      males. The presence of p53, bcl-2 and latent membrane protein-1 (LMP-1) of EBV
      expression was studied by immunohistochemistry and Epstein Barr encoded RNAs
      (EBERs) by in situ hybridization in tissue sections from formalin-fixed, paraffin
      embedded NPC biopsies RESULTS: EBV presence and LMP-1 expression in epithelial
      tumor cells were detected in all the biopsies studied. p53 was expressed in 13/16
      NPCs, but the frequency of positive malignant cells differed from case to case,
      ranging from less than 25 to 100% with heterogeneous staining intensity. Bcl-2
      positive staining in tumor epithelial cells was detected in 2/16; whereas 10/16
      cases showed bcl-2 positivity in infiltrating lymphocytes. CONCLUSIONS: Although
      our series is small, we conclude that the pathogenesis of pediatric NPC as a
      multistep process may well involve EBV infection. This leads to LMP-1 expression
      and p53 overexpression in epithelial tumor cells, whereas bc-2 seems unrelated to
      the development of this disorder.

PMID- 11979460
TI  - Topical topic: accidental cisplatin overdose in a child: reversal of acute renal
      failure with sodium thiosulfate.

PMID- 11979461
TI  - Editorial: chemotherapy errors in oncology.

PMID- 11979462
TI  - Misleading leads: don't assume an alpha-fetoprotein secreting tumour is of germ
      cell or hepatic origin.

PMID- 11979463
TI  - Issues concerning the treatment of a child with a craniopharyngioma.

PMID- 11979464
TI  - Third joint meeting of Rumanian and Hungarian pediatric
      hematologists/oncologists.

PMID- 11979465
TI  - Topical topics: pitfalls of "long-distance pharmacokinetics." Shipment of
      biologic samples to reference laboratories.

PMID- 11979466
TI  - Brief report: successful therapy of a patient with infantile generalized
      myofibromatosis.

PMID- 11979467
TI  - Brief report: biliary emesis as the presenting sign in a neonate with Wilms
      tumor.

PMID- 11979488
TI  - Fractional factorial designs for legal psychology.
AB  - Researchers considering novel or exploratory psycholegal research are often able
      to easily generate a sizable list of independent variables (IVs) that might
      influence a measure of interest. Where the research question is novel and the
      literature is not developed, however, choosing from among a long list of
      potential variables those worthy of empirical investigation often presents a
      formidable task. Many researchers may feel compelled by legal psychology's heavy
      reliance on full-factorial designs to narrow the IVs under investigation to two
      or three in order to avoid an expensive and unwieldy design involving numerous
      high-order interactions. This article suggests that fractional factorial designs
      provide a reasonable alternative to full-factorial designs in such circumstances
      because they allow the psycholegal researcher to examine the main effects of a
      large number of factors while disregarding high-order interactions. An
      introduction to the logic of fractional factorial designs is provided and several
      examples from the social sciences are presented.

PMID- 11979489
TI  - How psychiatrists and judges assess the dangerousness of persons with mental
      illness: an 'expertise bias".
AB  - When assessing dangerousness of mentally ill persons with the objective of making
      a decision on civil commitment, medical and legal experts use information
      typically belonging to their professional frame of reference. This is
      investigated in two studies of the commitment decision. It is hypothesized that
      an 'expertise bias' may explain differences between the medical and the legal
      expert in defining the dangerousness concept (study 1), and in assessing the
      seriousness of the danger (study 2). Judges define dangerousness more often as
      harming others, whereas psychiatrists more often include harm to self in the
      definition. In assessing the seriousness of the danger, experts tend to be more
      tolerant with regard to false negatives, as the type of behavior is more familiar
      to them. The theoretical and practical implications of the results are discussed.

PMID- 11979490
TI  - Murderers' and sexual offenders' experiences of police interviews and their
      inclination to admit or deny crimes.
AB  - This research concerns murderers' and sexual offenders' experiences of Swedish
      police interviews and their attitudes towards allegations of these serious
      crimes. The explorative study is based on a questionnaire answered by 83 men
      convicted of murder or sexual offences. Results show that when police officers
      interview murderers and sexual offenders, the individuals perceive attitudes that
      are characterized by either dominance or humanity. Logistic regression shows that
      police interviews marked by dominance are mainly associated with a higher
      proportion of denials, whereas an approach marked by humanity is associated with
      admissions. When suspects feel that they are respected and acknowledged, they
      probably gain more confidence and mental space, allowing them to admit criminal
      behaviour.

PMID- 11979491
TI  - The defense of extreme emotional disturbance in New York County: pleas and
      outcomes.
AB  - A number of studies have investigated the use of the insanity defense; however,
      there are few reports on the use of other types of psychiatric defenses. This
      study explored the use of the affirmative psychiatric defense of extreme
      emotional disturbance (EED) in New York County (one of the five counties which
      comprise New York City). The results of the study indicate that, as in the case
      of the insanity defense, EED is rarely proffered by criminal defendants (plea
      rate 0.84%). The defense only prevailed on one occasion at a jury trial. While
      the EED defense was successful 39% of the time that it was entered, this was
      usually only when the prosecutor accepted the argument that was offered by the
      defense.

PMID- 11979492
TI  - Attorney-client trust among convicted criminal defendants: preliminary
      examination of the attorney-client trust scale.
AB  - The current study describes the development of the Attorney-Client Trust Scale
      (ACTS), a measure designed to assess a client's trust in his or her attorney. A
      sample of 307 male inmates completed the ACTS and provided information about
      their most recent case and attorney. Low ACTS scores were associated with having
      a court-appointed attorney, going to trial, and receiving a lengthy prison
      sentence. High ACTS scores were related to satisfaction with sentences and
      attorneys. In addition, findings suggest that perceptions about attorneys'
      interpersonal skills were as important as perceptions about legal skills in
      forming opinions about overall lawyering ability. It is recommended that
      attorneys employ a well rounded assortment of interpersonal skills to foster
      their clients' trust and to make better use of the limited amount of time they
      have to spend with clients.

PMID- 11979493
TI  - Trust and understanding in the attorney-juvenile relationship.
AB  - This study investigated whether court-experienced juveniles differ from court
      experienced adults in their understanding of the defense counsel role and their
      trust in attorneys. Court-experienced juveniles and young adults, ages 12 to 20,
      were compared on measures of trust, attitudes toward authority, understanding
      about the role of defense counsel, trial-related knowledge, and the Trust in My
      Lawyer Scale. The findings showed that court-related knowledge is associated with
      both level of intellectual functioning and age and that court-related
      misunderstandings are associated with mistrust in attorneys. The findings did not
      support the assertion that there are significant differences between juveniles
      and young adults in their trust of their attorneys. Results regarding parental
      involvement, attorney characteristics, and interaction effects of race and
      intellectual functioning in relation to trust are also discussed.

PMID- 11979494
TI  - Predicting the home location of serial offenders: a preliminary comparison of the
      accuracy of human judges with a geographic profiling system.
AB  - The accuracy with which human judges, before and after 'training', could predict
      the likely home location of serial offenders was compared with predictions
      produced by a geographic profiling system known as Dragnet. All predictions were
      derived from ten spatial displays, one for each of ten different U.S. serial
      murderers, indicating five crime locations. In all conditions participants were
      asked to place an 'X' on each spatial display corresponding to where they thought
      the offender lived. In the control condition, a comparison was made between the
      accuracy of these predictions for 21 participants on two separate occasions a few
      minutes apart. In the experimental condition, between their first and second
      predictions the 21 participants were given two heuristics to follow--distance
      decay and circle hypothesis. Results showed that participants with no previous
      knowledge of geographic profiling were able to use the two heuristics to improve
      the accuracy of their predictions. The overall accuracy of the second set of
      predictions for the experimental group was also not significantly different from
      the accuracy of predictions generated by Dragnet.

PMID- 11979495
TI  - The psychology of telling murder stories: do we think in scripts, exemplars, or
      prototypes?
AB  - According to the story model of Pennington and Hastie, jurors collect information
      at trial and modify it with general knowledge to create case stories. Schank and
      Ableson argue that human memory is organized to tell and understand stories.
      However, Finkel and Groscup questioned the use of manipulated, experimenter
      constructed narratives to demonstrate the existence of multiple prototypical
      crime stories. We interviewed 76 jury eligible, death qualified citizens and
      asked them to imagine a first-degree murder scenario, describing the events that
      led to the killing. We coded the presence of dichotomous variables in the
      resulting stories and identified at least three shared story prototypes using
      cluster and profile analysis. We conclude that people do not store crime stories
      as simple prototypes and comment on the implications of this finding for legal
      decision-making.

PMID- 11979496
TI  - Equality in hiring permanent resident foreign nationals in the United States:
      when loyalty is the question, but not the issue.
AB  - Permanent resident foreign nationals, who have been legally admitted to the
      United States, have the right to work. However, when deciding the
      constitutionality of a state statute that requires citizenship for a public
      domain job, the rights of permanent residents to seek gainful employment are
      balanced against the rights of state governments to ensure that important
      sovereign functions are entrusted only to their citizens. Several important
      Supreme Court decisions have been 5/4 split decisions because of this tension and
      dissenting judges have countered that the majority rulings were based on
      presumptions, and not facts, that citizens are more loyal than permanent
      residents. The judges have also disagreed about the level, within a civil service
      hierarchy, below which a citizenship requirement is unconstitutional. This
      article reviews United States court decisions for relevant issues and solutions,
      and shows how empirical studies in the area of human resource management can help
      resolve the issues that have caused the dissent. The analysis will be useful to
      legal and human resource professionals in the U.S. and other countries affected
      by surging global migration.

PMID- 11979497
TI  - What do we really know about witness preparation?
AB  - Witnesses often meet with an attorney or witness preparation specialist before
      trial to review, discuss, and sometimes modify the substance and delivery of
      their anticipated testimony. This process is commonly referred to as witness
      preparation. During witness preparation, witnesses are taught to use effective
      testimony delivery skills (e.g., verbal and nonverbal communication skills) so
      that they will be perceived as being credible and persuasive in the courtroom.
      Although social scientists know much about communication skills, credibility, and
      persuasion, few published studies have attempted to determine whether or not
      these factors can be modified through witness preparation training. The present
      article reviews the psychological literature pertaining to witness preparation
      and makes recommendations for needed witness preparation research.

PMID- 11979498
TI  - Death row inmate characteristics, adjustment, and confinement: a critical review
      of the literature.
AB  - This article reviews and summarizes research on death row inmates. The
      contributions and weaknesses of death row demographic data, clinical studies, and
      research based on institutional records are critiqued. Our analysis shows that
      death row inmates are overwhelmingly male and disproportionately Southern. Racial
      representation remains controversial. Frequently death row inmates are
      intellectually limited and academically deficient. Histories of significant
      neurological insult are common, as are developmental histories of trauma, family
      disruption, and substance abuse. Rates of psychological disorder among death row
      inmates are high, with conditions of confinement appearing to precipitate or
      aggravate these disorders. Contrary to expectation, the extant research indicates
      that the majority of death row inmates do not exhibit violence in prison even in
      more open institutional settings. These findings have implications for forensic
      mental health sentencing evaluations, competent attorney representation,
      provision of mental health services, racial disparity in death sentences, death
      row security and confinement policies, and moral culpability considerations.
      Future research directions on death row populations are suggested.

PMID- 11979500
TI  - Effects of vitamin A and insulin on the antioxidative state of diabetic rat
      heart: a comparison study with combination treatment.
AB  - Because elevated oxidative stress may exacerbate cardiovascular complications of
      diabetes mellitus, the current study aimed to investigate the effects of
      treatment with either vitamin A, an antioxidant, or with insulin on lipid
      peroxidation products and antioxidant enzyme activities of diabetic rat heart.
      Also to evaluate whether a combination of vitamin A and insulin exerts more
      beneficial effects than treatment with each agent alone. Rats were made diabetic
      with a single injection of streptozotocin (STZ, 55 mg kg(-1) i.p.). Two days
      after STZ-injection, one group of diabetic rats was treated with vitamin A
      (retinol acetate, 30 mg kg(-1) day(-1) i.o.) for 12 weeks. A second group of
      diabetic rats was untreated for 6 weeks and then treated for another 6 weeks with
      insulin (8-10 IU rat(-1) day(-1) s.c.). Both therapies were applied to another
      group of diabetic rats for assessment of combined therapy with vitamin A plus
      insulin. Hearts from 12-week untreated diabetic animals showed about a four-fold
      increase in the level of thiobarbituric acid reactive substances (TBARS),
      indicative of increased lipid peroxidation. This was accompanied by approximately
      100% increase in both catalase and glutathione peroxidase (GSHPx) enzyme
      activities. Therapy with insulin alone caused a small but significant improvement
      in plasma TBARS as well as GSHPx activities, but no significant change in plasma
      catalase in diabetic animals. Diabetes-induced disturbance in TBARS was almost
      completely prevented by vitamin A therapy. Although, a similar degree of
      activities for GSHPx was determined in diabetic animals treated with each agent
      alone, combination therapy was found to be more effective than single therapies
      in the recovery of GSHPx of diabetic heart. In contrast to insulin single
      therapy, vitamin A alone significantly prevented an increase in catalase activity
      of diabetic heart, and a combination of these agents did not supply any further
      benefit. Superoxide dismutase (SOD) activity was not found significantly
      different among the experimental groups. STZ-diabetes also resulted in less
      plasma retinol and retinol-binding protein (RBP), which was significantly
      improved by insulin single therapy while vitamin A used alone, failed to increase
      plasma retinol and RBP levels of diabetic animals. Our findings suggest that
      single therapy with insulin is unable to preclude oxidative reactions in diabetic
      heart to the same extent as obtained by vitamin A therapy alone, in spite of
      allowing recovery of normal growth rate and improved vitamin A metabolism in
      diabetic rats. A combination of insulin with vitamin A may provide more benefits
      than use of either agent alone in the treatment of general characteristics of
      diabetes and the maintenance of antioxidant defence of diabetic heart and thus in
      the reduction of peroxidative stress-induced cardiac injury.

PMID- 11979501
TI  - Evidence that glutamine is involved in neutrophil function.
AB  - Phosphate-dependent glutaminase (PDG) activity, a key enzyme of glutamine
      metabolism, was determined in neutrophils obtained from the intra-peritoneal
      cavity (PC) or bronchoalveolar space (BAS) after administration of 1 ml or 100
      microl, respectively of saline, glycogen solution (1%) or lipopolysaccharide (LPS
      0.1 mg (100 microl)(-1)). Neutrophils were obtained by lavage of both sites with
      20 ml saline 24 h after the administration of the stimuli. Glycogen and LPS,
      depending on the site the cells were obtained from, differently modulated PDG
      activity. Cells from BAS stimulated by glycogen or LPS had raised PDG activity to
      30.5 +/- 5.2 and 42.7 +/- 12.1 nmol min(-1) mg(-1) protein, respectively, when
      compared with saline (9.1 +/- 0.9 nmol min(-1) mg(-1) protein); mean +/- SEM. On
      the other hand, cells from PC showed different PDG activity: 52.0 +/- 12.6 nmol
      min(-1) mg(-1) for saline, 36.5 +/- 9.5 nmol min(-1) mg(-1) for glycogen, and
      76.6 +/- 11.2 nmol min(-1) mg(-1) for LPS; mean +/- SEM. Therefore, PDG activity
      varies with the site from which neutrophils are obtained and the stimulus
      imposed. The effect of glutamine on nitric oxide (NO) and tumour necrosis factor
      (TNF) production by peritoneal neutrophils, obtained after glycogen
      administration, cultured in the presence of LPS (0.5 microg ml(-1)) was also
      examined. The addition of glutamine at concentrations varying from 2 to 20 mM did
      not markedly affect NO production. Glutamine alone at 2 mM did not modify the
      production of TNF but in the presence of LPS caused a significant decrease. So,
      glutamine may preserve the function of neutrophils during infections and
      injuries.

PMID- 11979502
TI  - Monoamine oxidase A and B activities in embryonic chick hepatocytes: differential
      regulation by retinoic acid.
AB  - Monoamine oxidases (MAOs) A and B are two isoenzymes involved in the degradation
      of many biological amines in the nervous system and in peripheral organs. In the
      present work hepatocytes isolated from 14-day-old chick embryos were used as a
      model system to determine whether retinoic acid (RA) is capable of modulating the
      activity of the two MAO forms. RA is a retinoid that, by binding with nuclear
      receptors, interferes with the expression of specific genes in many
      differentiation processes. Enzymic activity was measured with a radiochemical
      method using serotonin and beta-phenylethylamine as preferential substrates for
      MAO A and MAO B, respectively. The specific activity of the two forms was
      measured in hepatocytes cultured for 24, 48 and 72 h in the presence and the
      absence of serum. RA stimulated MAO B but not MAO A activity, in a dose- and time
      dependent way, and only in the presence of serum. Maximum stimulation (about 3.5
      fold) was obtained after treatment with 5 microM RA for 72 h. Kinetic analysis of
      MAO B activity showed an increase in V(max) in treated hepatocytes (5 microM RA
      for 72 h) with no change in K(m). In conclusion, the present work shows that RA
      selectively elicits MAO B activity in cultured chick embryonic hepatocytes, this
      stimulation requires the presence of some factors present in the serum and is
      probably due to an increase in the number of enzyme molecules.

PMID- 11979503
TI  - Effect of vitamin C and zinc on osmotic fragility and lipid peroxidation in zinc
      deficient haemodialysis patients.
AB  - Peroxidation of the membrane lipid structure of red blood cell leads to
      haemolysis and anaemia in haemodialysis patients. Dietary constituents of
      antioxidant vitamins and trace elements may play an important role in protecting
      against oxidant damage. In this study, the effects of supplementation of vitamin
      C and zinc on osmotic fragility and lipid peroxidation of erythrocytes were
      investigated in 34 zinc-deficient haemodialysis patients. Sixteen sex- and age
      matched normal volunteers acted as controls. Patients were randomized to receive
      vitamin C (250 mg day(-1)), zinc (20 mg day(-1)) or a placebo treatment for 3
      months. The levels of vitamin C, zinc, malondialdehyde (MDA) and osmotic
      fragility were measured initially and 3 months after supplementation. Mean serum
      concentration of vitamin C and zinc increased significantly in the groups at the
      end of the respective study periods. Supplementation with vitamin C and zinc
      improved osmotic fragility, and decreased the level of MDA in the groups, but
      some side-effects (i.e. nausea, vomiting, fever, muscle pain, weakness) were
      observed during the zinc treatment. The results showed that the supplementation
      of both treatments decreased osmotic fragilty and MDA in zinc-deficient
      haemodialysis patients. However, vitamin C treatment was found to be safer than
      zinc supplementation.

PMID- 11979504
TI  - Sulphydryl groups involved in Na+-Li+ exchange in human erythrocytes.
AB  - Oxidative stress causes cellular injury that is thought to be due to increased
      cytosolic cation levels. Disturbances of a variety of mechanisms which normally
      maintain intracellular anion/cation homeostasis, occur during oxidative stress.
      Reactivity of the SH- groups essential for oubain-resistant Na(+)-Li(+) exchange
      by N-ethylmaleimide (NEM) and selenite was studied in human erythrocytes. In
      addition, the reactivity of the substances on SH- groups and Li(+) influx have
      been studied as a function of pH of the medium. The results show that NEM induces
      an irreversible inhibition of Li(+) influx. It diminishes progressively with the
      increasing pH of the medium. Whereas we obtain increasing intracellular Li(+)
      concentration with the rising selenite concentration in the medium. The maximum
      effect with this substance is reached at about pH 8.0. We can state that the -SH
      reagents (NEM and selenite) studied behave differently: NEM inhibits Li(+) influx
      by modifying the essential SH-groups of the membrane proteins in such a way that
      the exchange is reduced, whereas it maintains the Na(+) permeability almost
      unaltered. The slight increase in intracellular Na(+) induced by selenite
      suggests that the oxidative changes in the intracellular sulphydryl groups may
      constitute an important mechanism for the regulation of the intracellular
      cations.

PMID- 11979505
TI  - The effect of calcitonin treatment on plasma nitric oxide levels in post
      menopausal osteoporotic patients.
AB  - Several recent studies have revealed a wide role for nitric oxide (NO) in bone
      metabolism. Low doses of NO cause bone resorption, but higher doses of NO inhibit
      bone resorbing activity. Cytokines are potent stimulators of NO production. NO is
      a very short-lived molecules. It exists for only 6-10 s only before it is
      converted by oxygen and water into the end-products nitrates and nitrites.
      Osteoporosis is a metabolic bone disease, characterized by a decreased amount of
      bone and increased susceptibility to fracture. NO may be involved as a mediator
      of bone disease such as post-menopausal osteoporosis. Calcitonin is a peptide
      hormone that inhibits bone resorption. The function of calcitonin in some cells
      is often unclear. In this study 30 post-menopausal osteoporotic women of ages
      ranging between 55 and 59 years without systemic diseases and free of any drug
      therapy were included. Twenty of them, randomly chosen, were treated with calcium
      (500 mg day(-1))+calcitonin (nasal spray 100 U day(-1)) and the other 10 women
      (control group) were treated with calcium only. This treatment was applied for 6
      months and NO values were measured in each of the two groups before and after
      treatment. Our findings demonstrate that NO regulates osteoclastic bone
      resorption activity in association with calcitonin.

PMID- 11979506
TI  - Walker 256 tumour growth causes marked changes of glutamine metabolism in rat
      small intestine.
AB  - The effect of Walker 256 tumour growth on the metabolism of glucose and glutamine
      in the small intestine of rats was examined. Walker 256 tumour has been
      extensively used as an experimental model to induce cancer cachexia in rats.
      Walker 256 tumour growth decreased body weight and small intestine weight and
      length. The activities of glucose-6-phosphate dehydrogenase and phosphate
      dependent glutaminase were reduced in the proximal, median and distal portions of
      the intestine. Glutamine oxidation was reduced in the proximal portion only. The
      decrease in glutaminase activity was not due to a low synthesis of the protein as
      indicated by Western blotting analysis. Hexokinase and citrate synthase
      activities were not changed by the tumour. These findings led us to postulate
      that tumour growth impairs glutamine metabolism of small intestine but the
      mechanism involved remains to be elucidated.

PMID- 11979507
TI  - Comparison of the selenium level with GSH-Px activity in the liver of mice
      treated with 7,12 DMBA.
AB  - In this study, the relationship between selenium (Se) and glutathione peroxidase
      (GSHPx) levels was investigated in 7,12-dimethylbenz(a)anthracene (7,12-DMBA)
      treated mouse liver. The potential mammary carcinogen 7,12-DMBA, was injected
      intraperitoneally (20 mg kg(-1) day(-1)) into 10-12 month old female mice. After
      21 days of application the mice were sacrificed and GSHPx and Se levels of liver
      homogenates were measured. Se and GSHPx levels in 7,12-DMBA-treated mice were
      significantly lower than those of controls (p < 0.05). The control group
      exhibited 0.9 +/- 0.066 U mg(-1) protein and 0.86 +/- 0.058 p.p.m. levels of
      GSHPx and Se respectively. The 7,12-DMBA-treated group had significantly (p <
      0.05) decreased GSHPx and Se levels (0.42 +/- 0.062 U mg(-1) protein and 0.69 +/-
      0.034 p.p.m. respectively). The results show a direct relationship between Se and
      GSHPx activity and a negative correlation between antioxidant capacity and
      existence of a carcinogen in metabolism.

PMID- 11979508
TI  - dELL, a drosophila homologue of transcription elongation factor ELL (Eleven
      nineteen Lysine rich Leukemia), is required for early development.
AB  - ELL (Eleven-nineteen Lysine rich Leukemia) is known to be an elongation factor
      resembling elongin for RNA polymerase II transcription. A homologue of human ELL
      (hELL) was identified in Drosophila melanogaster (dELL) and several cDNA clones
      were isolated from the embryonic cDNA library. We showed that dELL is expressed
      mainly in the ovaries and early embryonic stages by developmental Northern blot.
      dELL encodes a protein of 912 amino acids which is substantially longer than the
      hELL (612 aa). Immunostaining revealed that dELL was localized to nuclei in early
      embryos and to nuclei of nurse cells and follicle cells in the ovary suggesting
      its important role in early development of drosophila. To elucidate the function
      of this gene in drosophila, P-element mobilization was performed by utilizing a P
      element inserted upstream of dELL. Southern analysis showed that isolated mutants
      are internal P-element deletions. These P-element deletions can now be used to
      isolate dELL mutations by EMS mutagenesis.

PMID- 11979509
TI  - Characterization of the living skin equivalent as a model of cutaneous re
      epithelialization.
AB  - The living skin equivalent, a three-dimensional organotypic model, has been
      widely used to investigate many aspects of cutaneous biology. However, there are
      relatively few studies assessing how faithfully the skin equivalent reproduces
      normal skin biology. The skin equivalent was fabricated by seeding human
      epidermal keratinocytes onto the upper surface of a hydrated collagen lattice
      populated with human dermal fibroblasts and subsequently raised to the air-liquid
      interface where keratinocyte stratification and differentiation led to the
      formation of a tissue which showed many common morphological features to that of
      normal skin. Histology and immunohistochemical detection of keratinocyte
      integrins and matrix metalloproteinases (MMPs) were used as cytological markers
      to assess the accuracy of the model during cutaneous re-epithelialization.
      Analysis of expression of keratinocyte integrins revealed that whilst there were
      a number of similarities to normal skin, skin equivalent keratinocytes appeared
      to be 'activated' and hyper-proliferating. Wounding of the skin equivalent, by
      complete bisection, induced re-epithelialization from both wound edges within 8
      12 h, which completely restored the epidermis within 4 days. This migration, like
      that in vivo, was associated with nascent expression of MMPs and upregulation of
      certain integrins. However, whilst integrin expression, was similar to in vivo re
      epithelialization, there were subtle differences in the level of expression and
      distribution of certain integrins.

PMID- 11979510
TI  - Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and
      DT-diaphorase in different tissues of mice: a possible mechanism of action.
AB  - The present investigation focused, firstly, on the effects of oral administration
      of thymoquinone (TQ) on antioxidant enzyme activities, lipid peroxidation and DT
      diaphorase activity in hepatic, cardiac and kidney tissues of normal mice.
      Superoxide dismutase (SOD; E.C:1.15.1.1), catalase (CAT; E.C:1.11.1.6),
      glutathione peroxidase (GSH-Px; E.C:1.11.1.9), glutathione-S-transferase (GST;
      E.C:2.5.1.18), and DT-diaphorase (E.C:1.6.99.2) enzyme activities in each tissue
      type were determined. Treatment of mice with the different doses of TQ (25, 50
      and 100 mg kg(-1) day(-1) orally) for 5 successive days, produced significant
      reductions in hepatic SOD, CAT and GSH-Px activities. In addition cardiac SOD
      activity was markedly inhibited with the higher doses of TQ, (namely 50 and 100
      mg kg(-1)). Moreover, TQ (100 mg kg(-1)) significantly reduced hepatic and
      cardiac lipid peroxidation as compared with the respective control group.
      Conversely, TQ (50,100 mg kg(-1)) and TQ (100 mg kg(-1)) enhanced cardiac and
      renal DT-diaphorase activity respectively. However, the selected doses of TQ
      neither produced any change in GST activity nor influenced reduced glutathione
      content in all tissues studied. TQ was tested, secondly, as a substrate for
      hepatic, cardiac and renal DT-diaphorase of normal mice in the presence of NADPH.
      Kinetic parameters for the reduction of TQ to dihydrothymoquinone (DHTQ)
      indicated that DT-diaphorase of different tissues can efficiently reduce TQ to
      DHTQ. K(m) and V(max) values revealed that hepatic DT-diaphorase exhibited the
      higher values, while the lower values were associated with renal DT-diaphorase.
      TQ and DHTQ were tested, thirdly, as specific scavengers for superoxide anion
      (generated biochemically) or as general scavengers for free radicals (generated
      photochemically). The results revealed that TQ and DHTQ acted not only as
      superoxide anion scavengers but also as general free radical scavengers. The
      IC(50) for TQ and DHTQ in biochemical and photochemical assays were in the
      nanomolar and micromolar range respectively. Our data may explain at least partly
      the reported beneficial in vivo protective effects of TQ through the combined
      antioxidant properties of TQ and its metabolite DHTQ.

PMID- 11979511
TI  - Separation and purification of Echis coloratus venom and some biological and
      biochemical effects of the proteins.
AB  - Crude venom of Echis coloratus was separated into seven protein fractions using
      7% preparative native polyacrylamide gel electrophoresis. The effect of crude
      venom and seven venom protein fractions (F1-F7) from Echis coloratus on key
      metabolic activities of fibroblast cultures was investigated. Confluent cultures
      were incubated with the venom proteins for 3 h at 37 degrees C. The specific
      activity of phosphofructokinase, was significantly lowered upon incubation with
      the crude venom and with fractions 2, 3, 4 and 6. Citrate synthase activity was
      significantly lowered by the crude venom and by fractions 2 and 3. Glycogen
      phosphorylase activity was significantly increased by the crude venom and by
      fractions 2, 3, 4 and 6 leading to a significant concurrent drop in glycogen
      content. Creatine kinase activity was significantly increased by the crude venom
      and by fractions 3, 4, 5 and 6. Cellular ATP levels rose significantly upon
      incubation with the crude venom and with fractions 3, 4, 5 and 6. Incubation of
      cell sonicates with all the venom proteins did not significantly alter the
      activity or content of any of the studied parameters.

PMID- 11979512
TI  - Functional characterization of the 5' flanking region of human ubiquitin fusion
      degradation 1 like gene (UFD1L).
AB  - UFD1L (Ubiquitin Fusion Degradation 1 Like) gene encodes for a component of a
      multi-complex involved in the degradation of ubiquitin fusion proteins. The gene
      maps on chromosome 22q11, in a region commonly deleted in severe congenital
      disorders such as DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. UFD1L
      is a single copy gene ubiquitously expressed in high levels in the pharyngeal
      pouches and fourth branchial arch artery during development. To understand the
      regulation of UFD1L expression we performed a functional analysis of its 5'
      regulatory region. 5'-RACE and primer extension analyses revealed the presence of
      different transcription start sites in adult and fetal tissues. UFD1L 5' flanking
      region contains a TATA-box motif and is also very GC-rich with a CpG island
      encompassing exon 1. Transcriptional activity of this region was examined by
      transfection experiments of promoter-GFP reporter gene constructs in a human
      epithelial cell line. These experiments revealed the importance of the region
      between -17 and -463 nt which contains the TATA-box. EMSA assay resulted in the
      detection of five functional consensus sequences respectively for the
      transcription complex TFIID and for the transcription factors AP-1 (one site), AP
      2 (one) and Sp1 (two).

PMID- 11979513
TI  - Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia
      and bipolar disorder.
AB  - Recent data from several reports indicate that free radicals are involved in
      aetiopathogenesis of many human pathologies including neuropsychiatric disorders
      such as schizophrenia, bipolar disorder etc. In the present study, we aimed at
      determining and evaluating levels of malondialdehyde (MDA), a product of lipid
      peroxidation, and antioxidant enzyme superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) activity levels in patients diagnosed with schizophrenia (n =
      25) and bipolar disorder (n = 23). The control group was composed of 20 healthy
      subjects. There was a significant increase in MDA levels of patients with
      schizophrenia and bipolar disorder compared with controls. SOD and GSH-Px
      activity levels were significantly higher in the schizophrenic group compared
      with controls. SOD activity levels in bipolar the group were significantly higher
      than controls whereas there were no significant changes in GSH-Px activity levels
      in the bipolar group and controls. Significant differences between lipid
      peroxidation product and antioxidant enzyme (SOD and GSH-Px) activity levels in
      schizophrenic and bipolar disorder patients compared with controls leads us to
      believe that these differences are related to the heterogenities in aetiologies
      of these disorders.

PMID- 11979514
TI  - Effect of cerebrocrast on the function of human platelets and release of the
      arachidonic acid from plasma membrane.
AB  - Diabetes mellitus (DM) is accompanied by several cardiovascular complications
      such as coronary artery disease, atherosclerosis, hypertension, cerebral and
      myocardial infarction, etc. DM induces the alteration of platelet functions
      including activation, hyperaggregation, adhesiveness, and formation of thrombi.
      Release of AA from phospholipids of the PM, synthesis of TxA(2),PGE(2), activity
      of PLA(2), and PLC are increased in the platelets of the DM patients. Stimulation
      of PLA(2) activity and accumulation of bioactive metabolites such as AA, its
      oxygenated derivatives, prostaglandins and PAF can evoke glucose production,
      also. In this study we explored the effect of the 1,4-dihydropyridine compound
      cerebrocrast at a low concentration (10(-6)-10(-8)M) on the level of
      intracellular calcium in unstimulated human platelets and those stimulated with
      thrombin as well as release of [(3)H] AA from phospholipids of platelet PM.
      Cerebrocrast at a concentration of 10(-6) M decreased the basal level of
      intracellular calcium concentration (platelets were loaded with Fura-2) in
      unstimulated as well as in thrombin stimulated platelets. Cerebrocrast at
      concentrations of 10(-6), 10(-7), 10(-8) M inhibited release of [(3)H] AA from
      phospholipids of platelet PM. We conclude that blockade of human platelet
      activation with cerebrocrast can prevent aggregation, adhesion and formation of
      thrombi. The inhibition of [(3)H] AA release from phospholipids of platelet PM
      can prevent formation of eicosanoids such as TxA(2), PGG(2), and PGH(2) plus AA
      oxygenated derivatives. These effects of cerebrocrast are very significant in the
      treatment of DM-evoked cardiovascular complications.

PMID- 11979515
TI  - Excluded volume effects in gene stretching.
AB  - We investigate the effects excluded volume on the stretching of a single DNA in
      solution. We find that for small force F, the extension h is not linear in F but
      proportion to F(gamma), with gamma = (1 - nu)/nu, where nu is the well-known
      universal correlation length exponent. A freely joint chain model with the
      segment length chosen to reproduce the small extension behavior gives excellent
      fit to the experimental data of lambda-phage DNA over the whole experimental
      range. We show that excluded volume effects are stronger in two dimensions and
      derive results in two dimensions that are different from the three-dimensional
      results. This suggests experiments to be performed in these lower dimensions.

PMID- 11979516
TI  - Conformational preferences of substituted prolines in the collagen triple helix.
AB  - Researchers have recently questioned the role hydroxylated prolines play in
      stabilizing the collagen triple helix. To address these issues, we have developed
      new molecular mechanics parameters for the simulation of peptides containing 4(R)
      fluoroproline (Flp), 4(R)-hydroxyproline (Hyp), and 4(R)-aminoproline (Amp).
      Simulations of peptides based on these parameters can be used to determine the
      components that stabilize hydroxyproline over proline in the triple helix. The
      dihedrals F-C-C-N, O-C-C-N, and N-C-C-N were built using a N-beta-ethyl amide
      model. One nanosecond simulations were performed on the trimers [(Pro-Pro
      Gly)(10)](3), [(Pro-Hyp-Gly)(10)](3), [(Pro-Amp-Gly)(10)](3), [(Pro-Amp(1+)
      Gly)(10)](3), and [(Pro-Flp-Gly)(10)](3) in explicit solvent. The results of our
      simulations suggest that pyrrolidine ring conformation is mediated by the
      strength of the gauche effect and classical electrostatic interactions.

PMID- 11979517
TI  - Monte Carlo study of cycloamylose: chain conformation, radius of gyration, and
      diffusion coefficient.
AB  - Cyclic (1 --> 4)-alpha-D-glucan chains with or without excluded volume have been
      collected from a huge number (about 10(7)) of linear amylosic chains generated by
      the Monte Carlo method with a conformational energy map for maltose, and their
      mean-square radii of gyration <S(2)> and translational diffusion coefficients D
      (based on the Kirkwood formula) have been computed as functions of x (the number
      of glucose residues in a range from 7 to 300) and the excluded-volume strength
      represented by the effective hard-core radius. Both <S(2)>/x and D in the
      unperturbed state weakly oscillate for x < 30 and the helical nature of amylose
      appears more pronouncedly in cyclic chains than in linear chains. As x increases,
      these properties approach the values expected for Gaussian rings. Though excluded
      volume effects on them are always larger in cycloamylose than in the
      corresponding linear amylose, the ratios of <S(2)> and the hydrodynamic radius of
      the former to the respective properties of the latter in good solvents can be
      slightly lower than or comparable to the (asymptotic) Gaussian-chain values when
      x is not sufficiently large. An interpolation expression is constructed for the
      relation between the gyration-radius expansion factors for linear and cyclic
      chains from the present Monte Carlo data and the early proposed asymptotic
      relation with the aid of the first-order perturbation theories.

PMID- 11979518
TI  - Determination of intermolecular distance for a model peptide of Bombyx mori silk
      fibroin, GAGAG, with rotational echo double resonance.
AB  - Rotational echo double resonance NMR spectroscopy is applied for the
      determination of the distance of intermolecular chains of pentapeptide, GAGAG (G:
      Gly, A: Ala), a model typical of the crystalline domain in Bombyx mori silk
      fibroin. 1:4 mixture of G[1-(13)C]AGAG and GAG[(15)N]AG with antiparallel beta
      sheet structure was used to determine the distance of intermolecular hydrogen
      bonding between adjacent molecules within pleated sheet and the (13)C-(15)N
      interatomic distance was determined to be 4.3 A. On the other hand, 1:4 mixture
      of GAG[1-(13)C]AG and GAG[(15)N]AG gave information on the interpleated sheet
      arrangement. When we assumed the same distances between two interpleated sheets,
      the distance was calculated to be 5.3 A and the angle (15)N-(13)C-(15)N was 180
      degrees.

PMID- 11979519
TI  - New cross-linked and sulfated derivatives of partially deacetylated hyaluronan:
      synthesis and preliminary characterization.
AB  - Partial chemical deacetylation of hyaluronan (HA) has been carried out using
      known procedures and carefully controlled experimental conditions in order to
      minimize chain degradation. The sample described herein (deHA) has a degree of
      deacetylation of about 17%, which corresponds to what required for its further
      use, but a molecular weight of about 1/25 with respect to the native, starting
      material. Chemical gels have been prepared with different degrees of cross
      linking by means of a Ugi multicomponent condensation reaction involving aqueous
      deHA, formaldehyde, and cyclohexylisocyanide: the gels are mechanically stable
      and exhibit good water uptake strongly dependent on the extent of cross-linking,
      as expected. deHA samples have also been selectively N-sulfated or O-sulfated:
      the former exhibit anticoagulant properties well exceeding those of the latter
      and not too inferior to heparin.

PMID- 11979520
TI  - Surveying a local fitness landscape of a protein with epistatic sites for the
      study of directed evolution.
AB  - We present a method for analysis of a fitness landscape of a biopolymer with
      significantly epistatic sites. The analysis is based on a quasi-additive fitness
      model. The fitness model is constructed with additive terms conducted by "site
      fitness" and epistatic terms conducted by "pair-fitness," where the site-fitness
      is a fitness contribution from an independent residue and the pair-fitness is a
      fitness contribution from a pair of epistatic residues. As a case study, we
      analyzed the sequence-fitness data for 45 clones of thermostable prolyl
      endopeptidase mutants. They were generated by a mutation scrambling method, which
      can accumulate advantageous mutations. The fitness contributions from 14 single
      point mutations including E67Q and Q656R were identified by the analysis. As a
      result, we found that the fitness model with a significant epistatic term by a
      pair of the 67th site and 656th site was in good agreement with the experimental
      data and that the explored landscape in the binary 14-dimensional sequence space
      is still a mountainous landscape with twin peaks. The validity was supported by
      the analysis of mutant fitness distributions derived from another mutation
      scrambling experiment and by (3D) structural data.

PMID- 11979521
TI  - A metal binding in the polypeptide chain improves the folding efficiency of a
      denatured and reduced protein.
AB  - In order to examine the effect of a metal binding to the polypeptide chain on the
      aggregation of a protein in the refolding process, we prepared a mutant hen
      lysozyme possessing the same Ca(2+) binding site as in human alpha-lactalbumin by
      Escherichia coli expression system (Ser(-1) CaB lysozyme). In the presence of 2
      mM CaCl(2), the refolding yield of Ser(-1) CaB lysozyme at a low protein
      concentration (25 microg/mL) was similar to that of the wild-type lysozyme (80%),
      but that at high protein concentration (200 microg/mL) decreased (15%) due to
      aggregation comparing to that of the wild-type lysozyme (45%). However, the
      refolding yield of Ser(-1) CaB lysozyme in the presence of 100 mM CaCl(2) even at
      a protein concentration of 200 microg/mL was 80% and was higher than that of the
      wild-type lysozyme. From analysis of chemical shift changes of the cross peaks in
      the backbone region of total correlated spectroscopy (TOCSY) spectra of a
      decapeptide possessing the same calcium binding site as in Ser(-1) CaB lysozyme
      in the presence of various concentrations of Ca(2+), it was suggested that the
      dissociation constant of Ca(2+)-peptide complex was estimated to be 20-36 mM.
      Moreover, the solubility of the denatured Ser(-1) CaB lysozyme in the presence of
      100 mM CaCl(2) was higher than that in the presence of 2 mM CaCl(2) whereas the
      solubility of the denatured Ser(-1) lysozyme in the presence of 100 mM CaCl(2)
      was not higher than that in the presence of 2 mM CaCl(2). Therefore, it was
      concluded that the reduced lysozyme possessing the Ca(2+) binding site was
      efficiently folded in the presence of high concentration of Ca(2+) (100 mM) even
      at high protein concentration due to depression of aggregation by the binding of
      Ca(2+) to the polypeptide chain in Ser(-1) CaB lysozyme.

PMID- 11979522
TI  - Rheolytic thrombectomy with Angiojet in thrombus-containing lesions.
AB  - The AngioJet thrombectomy device removes thrombus by creating a negative pressure
      and causing fragmentation of the thrombus. The objective was to study the safety
      and efficacy of this thrombectomy device during coronary interventions and to
      report the results of our experience. We studied 72 patients (mean age, 64.9 +/-
      12.6 years; 79% males) who had an AngioJet procedure during coronary
      intervention; 33 (46%) had vein graft intervention. All patients had angiographic
      thrombus. Most patients presented either with unstable angina (54%) or acute
      myocardial infarction (32%) within 24 hr. The procedural success was high with
      AngioJet (93%). TIMI grade 3 flow was achieved in 79% of lesions treated with
      AngioJet. In-hospital mortality was 1.4%, death/Q-wave myocardial infarction was
      4.2%, and the composite endpoint of death and Q-wave myocardial
      infarction/revascularization was 5.6% for patients undergoing AngioJet. Subgroup
      analysis of patients with vein graft intervention demonstrated high procedural
      success in those undergoing AngioJet (91%). At 1-year follow-up of the successful
      percutaneous interventions with AngioJet, the mortality, death/Q-myocardial
      infarction, and composite endpoint rates were 10%, 13.3%, and 35.5%,
      respectively. Long-term event-free survival was worse in vein graft
      interventions. The incidence of death, death/myocardial infarction, or composite
      endpoints at 1 year was 16%, 19%, and 46%, respectively. High procedural success
      can be achieved with the AngioJet thrombectomy device in lesions containing
      thrombus. It is effective in both native coronary arteries and vein graft
      interventions. However, the long-term outcome of patients with vein graft
      intervention was worse.

PMID- 11979523
TI  - Percutaneous coronary intervention of thrombotic lesions: still challenging!

PMID- 11979524
TI  - Same-day transradial outpatient stenting with a 6-hr course of glycoprotein
      IIb/IIIa receptor blockade: a feasibility study.
AB  - The aim of the study was to explore the feasibility of same-day outpatient stent
      placement using a short course of intravenous antiplatelet therapy. Patients (n =
      26) had stent placement and 6 hr of eptifibatide therapy. Demographics,
      procedural information, CPK data, and length of stay were recorded along with
      postdischarge outcomes. Twenty-one men and five women with median age of 60 years
      (49, 69) underwent transradial stenting. Baseline characteristics included
      diabetes 62%, hyperlipidemia 77%, prior coronary bypass surgery 19%, and unstable
      angina 35%. There were no CPK elevations (> 2 x normal) or ECG changes. Discharge
      occurred after 6.5 hr (5.8, 7.0). Neither vascular site complications nor
      readmission for procedure-related problems occurred. One patient later expressed
      concerns about discharge education. Outpatient stent placement with 6-hr infusion
      of GP IIb/IIIa inhibitor appears feasible and efficient in select patients. There
      may be challenges to meet with regard to patient education. Further studies with
      larger populations are needed to evaluate and optimize this approach.

PMID- 11979525
TI  - Impatient for outpatient?

PMID- 11979526
TI  - Stenting for coronary artery spasm.
AB  - We evaluated coronary stenting in nine patients with clinically severe,
      angiographically documented spasm refractory to aggressive pharmacologic
      management. No patient subsequently developed unstable ischemia requiring
      hospitalization as a consequence of recurrent spasm within the stent. Mechanisms
      of therapeutic failure included both persistent spasm and spasm in a different
      artery in one patient. Restenosis occurred in three patients who subsequently
      underwent repeat revascularization. In the rare, carefully selected patient,
      stents may represent an adjunct in the management of focal coronary artery spasm,
      although currently medical therapy remains the standard initial approach.

PMID- 11979527
TI  - Percutaneous coronary intervention for variant angina: balloon vs. stent.

PMID- 11979528
TI  - Short- and long-term results of emergency and elective percutaneous interventions
      on left main coronary artery stenoses.
AB  - In this prospective study, we analyzed the short- and long-term outcomes of
      percutaneous interventions on significant left main coronary artery (LM)
      stenoses. Between January 1998 and June 2000, 18 patients underwent emergency
      interventions on unprotected LM stenoses (group 1), while 15 patients had
      elective interventions on protected LM stenoses (group 2). Despite a procedural
      success of 88.9% in group 1, event-free in-hospital and mortality rates were
      50.0% and 38.9%. After 6.4 +/- 4.4 months of follow-up, late event-free survival
      and mortality rates were 33.3% and 38.9%. In group 2, procedural success was
      100%, with 100% event-free in-hospital survival; late event-free survival and
      mortality rates were 93.3% and 0% after 6.7 +/- 4.1 months of follow-up.
      Emergency interventions on LM stenoses remain a procedure with high acute and mid
      term mortality. In spite of the high rate of major adverse cardiac events, an
      acceptable long-term survival can be achieved.

PMID- 11979529
TI  - Left main percutaneous intervention: the saga continues.

PMID- 11979530
TI  - Percutaneous reperfusion of left main coronary disease complicated by acute
      myocardial infarction.
AB  - Previous studies have shown a benefit of a strategy of direct angioplasty and
      stenting in patients with acute myocardial infarction (AMI) complicated by early
      cardiogenic shock. However, few data exist for the subset of patients with left
      main trunk disease complicated by AMI and cardiogenic shock. We performed an
      analysis of patients with AMI who underwent mechanical intervention between
      January 1995 and December 2000. Out of 1,433 patients with ST segment elevation
      AMI treated with primary coronary angioplasty (PTCA), 22 patients (1.5%) had left
      main disease (LMD) as the culprit lesion. Baseline characteristics were age, 66
      +/- 11 years; female gender, 9%; diabetes, 14%; previous myocardial infarction,
      14%; mean systolic blood pressure, 77 +/- 24 mm Hg; time to treatment, 4.8 +/-
      2.2 hr; TIMI 0-1, 77%; collateral flow (Rentrop grade >or= 2) 9%. The primary
      success rate was 91%. Primary stenting was performed in 17 patients (77%). The in
      hospital mortality rate was 50%. All deaths were due to refractory shock. The 6
      month survival rate was 41% +/- 1%, while the event-free survival rate was 27% +/
      10%. At 6-month follow-up, the mortality rate increased to 59%; the target
      vessel revascularization rate was 14%. A percutaneous mechanical intervention
      strategy in patients with left main disease complicated by AMI is feasible and
      effective, and patients discharged alive have a good mid-term prognosis.

PMID- 11979531
TI  - Long-term clinical outcome after implantation of medium Palmaz (biliary) stents
      in very large native coronary arteries.
AB  - Intracoronary stenting has been shown to improve acute and long-term clinical
      results compared with coronary angioplasty. However, clinical outcome after
      medium Palmaz biliary (PB) stent implantation in very large native coronary
      arteries (> 4 mm in diameter) is unknown. This study evaluated restenosis and
      long-term clinical outcome after PB stenting in large native coronary arteries.
      Between June 1993 and December 1998, 55 patients with 56 lesions were treated
      with PB stents. Intracoronary stent deployment was successful in all 56 vessels
      attempted (100%). The mean stenosis was reduced from 65% +/- 10% to 4% +/- 14%.
      In 48 of the 56 vessels (86%), vessel size was greater than 4.0 mm in diameter
      and the mean reference vessel diameter was 4.73 +/- 0.7 mm after stenting.
      Angiographic success was achieved in 100%. Five patients had postprocedural
      cardiac enzyme elevation. There was no periprocedural death, emergency coronary
      artery bypass surgery, repeat target lesion revascularization, or acute stent
      thrombosis. Long-term clinical follow-up at mean of 28 +/- 15 months was obtained
      in 96% of the patients. Clinical restenosis rate occurred in 18% of ostial (6/34)
      and 0% of nonostial (0/22) lesions (P < 0.0001) with an overall clinical
      restenosis rate of 11%. Repeat angioplasty were performed in these six patients.
      There were three cardiac and three noncardiac deaths. The overall event-free
      survival at 1 and 3 years was 92% +/- 4% and 80% +/- 6%, respectively. PB stent
      implantation in very large native coronary arteries can be performed with a high
      degree of procedural success and low in-hospital complications. The long-term
      clinical outcome of patients undergoing PB stenting is associated with excellent
      event-free survival. However, stenting of ostial lesions remains as an important
      factor for restenosis even in very large coronary artery stenting.

PMID- 11979532
TI  - Comparison of the self-expanding Radius stent and the balloon-expandable
      Multilink stent for elective treatment of coronary stenoses: a serial analysis by
      intravascular ultrasound.
AB  - We compared the outcome of the self-expanding Radius stent and the balloon
      expandable Multilink stent serially by angiography and intravascular ultrasound.
      Successful stent deployment was achieved in 66 lesions of 56 stable angina
      patients (34 lesions with Radius stents and 32 lesions with Multilink stents). At
      follow-up, there were no significant differences in minimal lumen diameter or
      percent diameter stenosis between the groups, nor in restenosis rates, although
      the Radius stent group rate was slightly lower (23.5% vs. 31.3%). In the Radius
      stent group, stent cross-sectional area (CSA) increased gradually after
      implantation until the 6-month follow-up (8.37 +/- 1.83 to 10.16 +/- 2.59 mm(2);
      n = 15), giving a larger CSA (P = 0.03) than the Multilink stent group, which
      decreased (9.00 +/- 2.05 to 8.27 +/- 2.15 mm(2); n = 17). The lumen CSA was also
      slightly larger (6.82 +/- 3.06 vs. 5.84 +/- 1.85 mm(2); P = 0.29) in the Radius
      stent group. These findings indicated that the Radius stent enlarged
      progressively after implantation, which might be useful for prevention of
      restenosis.

PMID- 11979533
TI  - A prospective single-center registry for the use of intracoronary gamma radiation
      in patients with diffuse in-stent restenosis.
AB  - Based on single-center prospective registry data, the study evaluates short- and
      long-term results of intracoronary gamma radiation in patients with diffuse in
      stent restenosis in the reality of routine clinical practice. Percutaneous
      coronary intervention and subsequent catheter-based irradiation with iridium-192
      was performed in 84 vessels (81 patients) with diffuse in-stent restenosis.
      Repeat coronary angiography was performed in 35 patients with clinical
      restenosis. With a mean follow-up of 12.0 +/- 0.5 months, major adverse cardiac
      events were observed in 29 (34.5%) patients, including 2 cases of cardiac death,
      3 myocardial infarctions, 21 target lesion revascularizations, and 4 target
      vessel revascularizations. Five of six patients with total occlusion of the
      target vessel at baseline developed target lesion restenosis. Late total
      occlusion of the target vessel was observed in four patients. The 1-year event
      free survival rate was 69.8%. Total occlusion of the target vessel at baseline
      was the single independent predictor of cardiac events at 1-year follow-up (P <
      0.001). In patients with a target lesion in the left anterior descending artery,
      predictors of cardiac events also included female sex (P = 0.014), current
      smoking (P = 0.014), stenting during brachytherapy session (P = 0.02), and
      smaller reference vessel diameter at baseline (P = 0.01). The results of our
      registry are similar to those of randomized trials. As applied in routine
      clinical practice, intracoronary gamma radiation is a feasible, safe, and
      effective tool in the treatment of diffuse in-stent restenosis. Late events in
      the entire group were predicted by total occlusion at baseline.

PMID- 11979534
TI  - Nondominant right coronary artery occlusion and ventricular tachyarrythmias.
AB  - It is usually considered that occlusion of a nondominant right coronary artery is
      not associated with significant consequences. We report two cases of nondominant
      right coronary artery occlusion that presented with sudden cardiac death. Timely
      intervention resulted in complete resolution of the ventricular arrhythmias. This
      highlights the need for greater vigilance in the recognition and treatment of
      these lesions.

PMID- 11979535
TI  - Systolic compression of the left anterior descending coronary artery: a case
      series, review of the literature, and therapeutic options including stenting.
AB  - Six cases in our institution of various presentations of left anterior descending
      (LAD) myocardial bridging were found on coronary angiography. Generally a benign
      condition, this finding can result in ischemia or infarction as seen in some of
      our cases. We found one case in which the bridge resulted in an anterior
      myocardial infarction in an elderly patient, one case with fixed stenoses at the
      entry and exit point of the bridge causing ischemia, another with vasospasm
      within the bridged segment, one case in which the patient was referred for
      intervention of a fixed stenosis which after intracoronary nitroglycerin (NTG)
      was found to be an LAD bridge, another case in which the thallium myocardial
      perfusion scan revealed a reversible anterior defect, and finally one case with
      anginal chest pain despite a normal coronary flow reserve proximal and distal to
      the bridged segment. Our treatments varied from stenting in three patients to
      medical therapy in the remaining patients. We concluded that a thorough
      evaluation in this population should include functional testing for ischemia,
      intravascular ultrasound to assess wall thickness, and coronary flow reserve
      measurements in order to determine the significance of the these bridges.
      Stenting may have a role in select patients. However, additional studies are
      needed.

PMID- 11979536
TI  - Stented bridge: another golden gate for the interventional cardiologist.

PMID- 11979537
TI  - Acute renal artery thrombosis treated by percutaneous rheolytic thrombectomy.
AB  - Renal artery thrombosis or embolus is a rare condition that may lead to
      hypertension and renal failure. Treatment options in the past have had limited
      success. We present a case which demonstrates the use of percutaneous rheolytic
      therapy with the Angiojet atherectomy catheter to treat this condition in the
      acute setting.

PMID- 11979538
TI  - Meralgia paresthetica: an unusual complication of cardiac catheterization via the
      femoral artery.
AB  - Nerve complications following cardiac catheterization via the femoral route are
      rare. We report a case of meralgia paresthetica, a mononeuropathy affecting the
      lateral cutaneous nerve of the thigh following uncomplicated cardiac
      catheterization and percutaneous intervention via this route.

PMID- 11979539
TI  - Radiofrequency perforation in the treatment of congenital heart disease.
AB  - Catheter-directed perforation of cardiac tissue with radiofrequency (RF) energy
      has expanded the horizon of the interventional cardiologist dealing with
      congenital heart disorders. The focus of the following discussion will be to
      detail the biophysical basis behind RF perforation and review its application in
      the management of congenital heart lesions.

PMID- 11979540
TI  - Coronary artery stenting.

PMID- 11979541
TI  - Not congenital atresia of the aortic isthmus, but acquired complete occlusion in
      congenital aortic coarctation.

PMID- 11979542
TI  - Percutaneous endocardial transfer and expression of genes to the myocardium
      utilizing fluoroscopic guidance.

PMID- 11979548
TI  - Spectral karyotyping in patients with acute myeloid leukemia and a complex
      karyotype shows hidden aberrations, including recurrent overrepresentation of
      21q, 11q, and 22q.
AB  - We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia
      and a complex karyotype containing one to nine abnormalities that were not fully
      identifiable by G-banding. SKY showed the origin of rings and unidentified
      material in unbalanced translocations in all cases and the origin of markers in
      most, allowing reinterpretation of 136 aberrations and discovery of three
      aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the
      interpretation of three balanced aberrations recognized by G-banding and
      identified another nine balanced aberrations, including a novel translocation
      involving the RUNX1 gene. Eleven of 32 deletions found by G-banding were shown to
      be cryptic translocations or insertions, including three of four chromosome 3
      deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes
      deemed lost entirely by G-banding, 63 (68%) were shown to be involved in
      structural aberrations. This was especially true for -21 (eight of eight
      patients), -5 (five of six patients), -20 (seven of nine patients), and -18 (six
      of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of
      segments from at least one chromosome in 21 patients. The most frequently
      overrepresented was 21q, found in eight patients, including four with high-level
      21q amplification. Fluorescence in situ hybridization showed that the RUNX1 gene
      was not the target of amplification in seven of these patients. Also frequently
      gained were 11q (in seven patients, including three with high-level MLL gene
      amplification) and 22q (in seven patients). We conclude that SKY considerably
      enhances the accuracy of karyotype interpretation, and that amplification of
      chromosomal material may play a greater role in leukemogenesis than has been
      recognized.

PMID- 11979549
TI  - The common fragile site FRA16D and its associated gene WWOX are highly conserved
      in the mouse at Fra8E1.
AB  - Recently, several common fragile sites (CFSs) have been cloned and characterized,
      including the two most frequently observed in the human population, FRA3B and
      FRA16D. In addition to their high frequency of breakage, FRA3B and FRA16D
      colocalize with genes crossing large regions of breakage. At FRA3B, the fragile
      histidine triad (FHIT) gene spans more than 1 Mb, and at FRA16D, the WWOX gene
      spans more than 750 kb. It has also been shown that in Mus musculus, a CFS
      Fra14A2 and the mouse Fhit gene are conserved in the orthologous region of the
      genome. In this study, we positioned the ortholog to WWOX (Wox1) at chromosome
      band 8E1 in the mouse genome. To determine whether, like Fra14A2 and Fhit, Fra8E1
      and Wox1 colocalized in the mouse, we prepared bacterial and yeast artificial
      chromosome probes, and we hybridized them to aphidicolin-treated mouse metaphase
      chromosomes. Our data demonstrate that Wox1 colocalizes with Fra8E1. Furthermore,
      the sequence from this region, including introns, is highly conserved over at
      least a 100-kb region. This evolutionary conservation suggests that the two most
      active CFSs share many features, and that CFSs and their associated genes may be
      necessary for cell survival.

PMID- 11979550
TI  - Genome profiles of familial/bilateral and sporadic testicular germ cell tumors.
AB  - In order to investigate the genetics of testicular germ cell tumors (TGCTs), we
      examined 33 TGCTs, including 15 familial/bilateral and 18 sporadic tumors, using
      comparative genomic hybridization. The frequencies of the histological subtypes
      were comparable between the two groups. Gains of the whole or parts of chromosome
      12 were found in 30 tumors (91%). Furthermore, increased copy number of the whole
      or parts of chromosomes 7, 8, 17, and X, and decreased copy number of the whole
      or parts of chromosomes 4, 11, 13, and 18 were observed in > or = 50% of the
      tumors. Sixteen smallest regions of overlapping changes were delineated on 12
      different chromosomes. The chromosomal copy numbers of familial/bilateral and
      sporadic TGCTs were comparable, suggesting similar genetic pathways to disease in
      both groups. However, significant differences were observed between the two main
      histological subgroups. Gains from 15q and 22q were associated with seminomas (P
      = 0.005 and P = 0.02, respectively), whereas gain of the proximal 17q (17q11.2
      21) and high-level amplification from chromosome arm 12p, and losses from 10q
      were associated with nonseminomas (P < 0.001, P = 0.04, and P = 0.03,
      respectively).

PMID- 11979551
TI  - Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell
      lymphoma/leukemia cell lines.
AB  - Chromosome band 6q21 is reported to be one of the most frequent target regions in
      T-cell lymphoma for both translocations and deletions. To explore whether the
      breakpoint clustering in T-cell malignancy indicates the presence of a common
      breakpoint region in 6q, we employed fluorescence in situ hybridization analysis
      using various YAC, BAC, and PAC clones aligned at 6q21-22. We identified two T
      cell lymphoma/leukemia cell lines with different differentiation stages that had
      breakpoints within the same novel gene, TCBA1 (T-cell lymphoma breakpoint
      associated target 1). In a T-cell lymphoblastic lymphoma cell line, HT-1, the
      TCBA1 fused to SUSP1 (SUMO-1-specific protease), creating a SUSP1-TCBA1 chimeric
      gene. However, in an adult T-cell leukemia cell line, ATN-1, no chimeric gene was
      detected, although aberrant TCBA1 transcripts were produced. We conclude that
      TCBA1 is a possible target gene for T-cell lineage-specific chromosome
      aberrations at 6q21.

PMID- 11979552
TI  - t(1;3)(p36;p21) is a recurring therapy-related translocation.
AB  - Chromosome bands 1p36 and 3p21 are known to be recurring breakpoints in therapy
      related (t-) leukemia. We identified a recurring translocation, t(1;3)(p36;p21),
      in eight patients with various hematologic malignancies: three patients with ALL,
      one with chronic myelogenous leukemia (CML) in accelerated phase (AP), two with
      MDS, and two with AML(M3). Five of the eight patients had a history of
      chemotherapy, including alkylating agents in three, before the translocation was
      detected. In two of these five patients, the t(1;3)(p36;p21) emerged only at
      relapse or in the accelerated phase of CML. The karyotypes of the patients were
      complex, including -7 and structural abnormalities of 5q, 6q, 7q, 9p, and 11q23.
      Survival time varied among patients (25 days to more than 16 years). Using FISH
      with 13 1p35-36 cosmid probes (tel-FB12-CA5-G7-FD2-CB1-ED8-FD9-G32-AE3-G50-AD8
      GG4-G43-cen), we delineated the 1p36 breakpoint in two patients with MDS and ALL
      as lying between FB12 and FD2 (between BAC47P3 and PAC963K15), with a small
      deletion near the breakpoint in both cases. In the patient with MDS, there was
      also a deletion at 3p21.3, as detected with the cosmid probe cosNRL9. The results
      of the present study suggest that t(1;3)(p36;p21) in hematologic diseases is
      associated with prior exposure to mutagens, including alkylating agents.

PMID- 11979553
TI  - Heterogenic molecular basis for loss of ABL1-BCR transcription: deletions in
      der(9)t(9;22) and variants of standard t(9;22) in BCR-ABL1-positive chronic
      myeloid leukemia.
AB  - The objective of this study was to characterize the ABL1-BCR fusion gene in 76
      BCR-ABL1-positive chronic myeloid leukemia (CML) patients regarding expression as
      well as genomic status, to assess the frequency of ABL1-BCR gene deletion in
      these patients, which has been reported to be an adverse prognostic factor in
      Philadelphia chromosome-positive CML. Patients were analyzed for ABL1-BCR 1b-b3
      and/or 1b-b4 transcription by RT-PCR analysis. ABL1-BCR gene status was analyzed
      by FISH in 16 CML patients with no ABL1-BCR transcript. FISH revealed a partial
      or total deletion of the ABL1-BCR gene in 9/16 and localized the 5' portion of
      ABL1 and the 3' portion of BCR at separated loci in 5/16 patients. The latter
      FISH pattern resulted from a nonreciprocal translocation in two and a complex
      translocation in three individuals. In 2/16 patients, FISH could not exclude an
      intact ABL1-BCR fusion gene. Thus, most CML patients without ABL1-BCR transcript
      could be characterized cytogenetically to belong to two major subgroups: a silent
      ABL1-BCR gene was attributed to a deletion in der(9)t(9;22) in 56% of the
      investigated patients or to variants of a standard t(9;22) (approximately 31%).
      Conversely, none of the 50 patients with an ABL1-BCR transcript exhibited a
      variant t(9;22) in GTG-banding analysis. Thus, genomic aberrations such as
      deletions or complex genomic rearrangements are the basic and most frequent cause
      for ABL1-BCR RNA negativity in CML. The heterogeneity of the underlying molecular
      mechanisms may explain divergent clinical implications described for patients
      with an ABL1-BCR deletion and those with no ABL1-BCR transcript.

PMID- 11979554
TI  - Uncovering novel inter- and intrachromosomal chromosome 1 aberrations in
      follicular lymphomas by using an innovative multicolor banding technique.
AB  - Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21), which is the
      initial genetic perturbation in this disease. Additional genetic mutations are
      required to generate a fully malignant phenotype. Secondary chromosomal
      alterations seen in FL include prominent involvement of chromosome 1 in the form
      of balanced or unbalanced translocations, insertions, deletions, and duplications
      involving both the p and q arms. We investigated a diagnostically well defined
      set of 55 t(14;18)-positive FL cases with complex karyotypes by means of
      multicolor karyotyping. Sixteen cases showed involvement of chromosome 1 and were
      analyzed in further detail by a novel multicolor banding technique for this
      chromosome. We defined three groups showing varying complexity of chromosome 1
      alterations. The first group revealed simple translocations, such as t(1;2),
      t(1;6), t(1;8), and t(1;17), involving breakpoints on either the p or the q arm
      of chromosome 1. The second group showed more complex rearrangements with
      translocations, insertions, regional duplications, and involvement of more than
      one partner chromosome with either the p or the q arm of chromosome 1. The third
      group was defined by highly complex rearrangements involving translocations,
      regional duplications, amplifications, and intrachromosomal band relocations
      affecting the entire chromosome 1. All three groups shared interchromosomal
      rearrangements of chromosome 1 with chromosome 8, often involving the MYC
      protooncogene site, amplification involving region 1q21-q31, and deletion
      involving region 1p36. Thus, the use of sophisticated multicolor molecular
      cytogenetic assays in the investigation of malignant lymphoma allows precise
      characterization of chromosomal alterations and will provide a better
      understanding of their biology.

PMID- 11979555
TI  - Detailed genomic mapping and expression analyses of 12p amplifications in
      pancreatic carcinomas reveal a 3.5-Mb target region for amplification.
AB  - Previous cytogenetic and comparative genomic hybridization (CGH) analyses have
      shown that the gain of chromosome arm 12p is frequent in pancreatic carcinomas.
      We investigated 15 pancreatic carcinoma cell lines using CGH, fluorescence in
      situ hybridization (FISH), and semiquantitative polymerase chain reaction (PCR)
      to characterize 12p amplifications in detail. The CGH analysis revealed gains of
      12p in four of the cell lines and local amplification within 12p11-12 in six cell
      lines. By FISH analysis, using precisely mapped YAC clones, the commonly
      amplified region was found to be approximately 5 Mb. The amplified segment
      extended from YAC 753f12, covering the KRAS2 locus, to YAC 891f1, close to the
      centromere. A semiquantitative PCR methodology was used to estimate genomic copy
      numbers of 14 precisely mapped expressed sequence tags (ESTs) and sequence-tagged
      sites, located within this interval. The level of amplification ranged from two-
      to 12-fold. The produced gene copy profiles revealed a 3.5-Mb segment with
      various local amplifications. This region includes KRAS2 and ranges from D12S1617
      to sts-N38796. Two of the cell lines (primary and metastatic tumor from the same
      patient) showed amplification peaks within the distal region of this segment, two
      had peaks within the proximal region, one showed subpeaks in both regions, and
      one displayed amplification of the entire region. Chromosome segment-specific
      cDNA array analysis of 29 expressed sequences within the whole interval between
      D12S1617 and sts-N38796 indicated overexpression of four ESTs, two corresponding
      to DEC2 and PPFIBP1, and two to ESTs with unknown function. Expression analysis
      of these and of KRAS2 showed specific overexpression in the six cell lines with
      local 12p amplifications. These findings indicate two target regions within the
      3.5-Mb segment in 12p11-12, one proximal including PPFIBP1, and one distal
      including KRAS2.

PMID- 11979556
TI  - Genetic differences detected by comparative genomic hybridization in head and
      neck squamous cell carcinomas from different tumor sites: construction of
      oncogenetic trees for tumor progression.
AB  - For a better understanding of genetic alterations in head and neck squamous cell
      carcinoma (HNSCC), we applied comparative genomic hybridization (CGH) in the
      analysis of 75 HNSCCs, comprised of 18 pharyngeal squamous cell carcinomas
      (PSCCs), 23 laryngeal squamous cell carcinomas (LSCCs), and 34 oral squamous cell
      carcinomas (OSCCs). The three subgroups of HNSCC showed significant differences
      in genetic alteration patterns. Overall, PSCC and LSCC had more copy number
      aberrations (CNAs) per tumor than did OSCC. Apparent differing patterns of high
      level amplification were also observed. The smallest recurrent chromosomal
      regions of high-level amplification (> or = 15% of cases) were 7q22, 8q24.1, and
      11q12-13 in PSCC and 3q26.1-29 in OSCC. According to single frequency and
      combined frequencies of CNAs, we concluded that the most important chromosomal
      events for progression of head and neck cancer were +3q, +5p, +8q, and -3p for
      all subgroups of HNSCC; additionally, +7q, +17q, -9p, and -13q for PSCC; +7p,
      +9q, +11q12-13, +14q, and +17q for LSCC; and +1p and +11q12-13 for OSCC. To
      identify further important genetic alterations and the relationships among the
      alterations, we constructed oncogenetic tree models for tumor progression of
      HNSCC from CGH data using branching and distance-based tree models. The tree
      models predicted that: (1) +3q21-29 was the most important early chromosomal
      event, and -3p, which occurred after +3q21-29, was also an important chromosomal
      event for all subsites of HNSCC; (2) +8q is the second most important early
      chromosomal event; (3) there may be at least three subgroups of HNSCC: one
      characterized by -3p, -9p, +7p, and -13q; another by +5p, +9qter, and +17p; and
      the other by +8q and +18p. These results suggest that different chromosomal
      aberrations may play a role in the initiation and/or progression of different
      subgroups of HNSCC.

PMID- 11979557
TI  - Suppression of the tumorigenic phenotype by chromosome 18 transfer into
      pancreatic cancer cell lines.
AB  - A number of lines of evidence have suggested that the long arm of chromosome 18
      apart from SMAD4 may carry a tumor-suppressor gene(s) that plays a role in the
      early stage of pancreatic ductal carcinogenesis. Thus, adenovirus-mediated
      introduction of SMAD4 does not suppress in vitro growth in cells with completely
      inactivated SMAD4, and frequent loss of 18q at the SMAD4 locus is observed in
      pancreatic cancers but no abnormalities of the normal SMAD4 homolog have been
      detected. In this study, we introduced a normal copy of chromosome 18 into some
      pancreatic ductal carcinoma cells with and without a complete inactivation of
      SMAD4. Both anchorage-dependent and -independent proliferation as well as
      invasiveness were significantly suppressed in the hybrid clones compared with
      that of their parental cells. Moreover, significant suppression of tumorigenesis
      was observed after inoculation in nude mice, irrespective of the SMAD4 status.
      Our present study provides the first functional evidence of the existence of an
      additional tumor-suppressor gene(s), other than SMAD4 and DCC, that is
      responsible for the pathogenesis in the early stage of pancreatic ductal
      carcinogenesis.

PMID- 11979558
TI  - Defective DNA-mismatch repair: a potential mediator of leukemogenic
      susceptibility in therapy-related myelodysplasia and leukemia.
AB  - We investigated the potential role of defective DNA-mismatch repair (MMR) as a
      mediator of leukemogenic susceptibility in patients with therapy-related
      myelodysplasia (t-MDS) and leukemia (t-leuk). Thirty-seven individuals with t
      MDS/t-leuk were analyzed for microsatellite instability (MSI), the hallmark of
      defective DNA-MMR. Using standardized international criteria, 5/37 (14%) patients
      displayed high MSI, whereas 3 other patients had low MSI (8%). To determine the
      stage at which MSI had developed, we analyzed the primary tumors of 12 patients.
      Three of 4 patients with high MSI t-MDS/t-leuk also had microsatellite unstable
      primary tumors. Conversely, MSI was not detected in any primary malignancy of
      patients with low MSI or microsatellite stable t-MDS/t-leuk (P = 0.0182). In the
      high MSI group, we further investigated genes targeted by defective DNA-MMR (BAX,
      TGFBRII, IGFIIR, Caspase-5, APC, PTEN, E2F4, MBD4, MSH6, and MSH3) in both
      primary tumor and t-MDS/t-leuk. However, no mutation was found in any gene. The
      significant association of MSI in t-MDS/t-leuk and corresponding primary tumors
      suggests that defective DNA-MMR confers leukemogenic susceptibility to this
      cohort of patients.

PMID- 11979559
TI  - Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related
      myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).
AB  - The t(11;20)(p15;q11) is a rare but recurrent translocation that so far has been
      described in only four acute myeloid leukemias (AMLs), two treatment-related
      myelodysplastic syndromes (t-MDSs), and one case of polycythemia vera. Recently,
      the t(11;20) was shown to result in a fusion of the NUP98 and TOP1 genes, with
      expression of the NUP98/TOP1 chimera encoded by the der(11)t(11;20), but not of
      the reciprocal TOP1/NUP98 on the der(20)t(11;20). The genomic breakpoints were
      subsequently mapped to introns 13 and 7 of NUP98 and TOP1, respectively. We
      present here a t-MDS with a three-way variant translocation,
      t(10;20;11)(q24;q11;p15), that generates a der(11)t(11;20) but not a
      der(20)t(11;20), strongly suggesting that the der(11) harbors the critical
      genetic rearrangement. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      revealed a NUP98/TOP1 fusion in which exon 13 of NUP98 was fused in-frame with
      exon 8 of TOP1. Extra long (XL) genomic PCR and subsequent sequence analyses
      showed that the breakpoint in NUP98 occurred at nucleotide (nt) 3461 of intron
      13, close to a MER (medium reiteration frequency interspersed repetitive element)
      repeat, and that the breakpoint in TOP1 was at nt 1436 of intron 7, downstream of
      a MIR (mammalian-wide interspersed repeats) repetitive element. Genomic XL PCR
      did not amplify the reciprocal TOP1/NUP98, nor was this chimera expressed, as
      expected from the cytogenetic finding. The present results provide further
      support for the involvement of the NUP98/TOP1 transcript, but not of the
      reciprocal one, in the development of MDS/AML. Furthermore, the three cases
      genomically characterized to date have all been treatment-related and have all
      harbored breakpoints in intron 13 of NUP98 and intron 7 of TOP1, suggesting that
      these introns are susceptible to chemotherapy-induced breakage.

PMID- 11979560
TI  - High-resolution 1H NMR spectroscopy in rat liver using magic angle turning at a 1
      Hz spinning rate.
AB  - It is demonstrated that a high-resolution (1)H NMR spectrum of excised rat liver
      can be obtained using the technique of magic angle turning (MAT) at a sample
      spinning rate of 1 Hz. A variant of the phase-corrected MAT (PHORMAT) pulse
      sequence that includes a water suppression segment was developed for the
      investigation. The spectral resolution achieved with PHORMAT approaches that
      obtained from a standard magic angle spinning (MAS) experiment at a spinning rate
      of several kHz. With such ultra-slow spinning, tissue and cell damage associated
      with the standard MAS experiment is minimized or eliminated. The technique is
      potentially useful for obtaining high-resolution (1)H spectra in live animals.

PMID- 11979561
TI  - High-resolution isotropic 3D diffusion tensor imaging of the human brain.
AB  - High-resolution cardiac-gated 3D diffusion tensor imaging (3D-DTI) is
      demonstrated in vivo for several areas of the human brain. Anatomical mapping of
      subcortical white matter (WM), as well as definition and identification of major
      WM bundles from the brainstem were performed in humans for the first time using
      this technique. Improved intrinsic signal-to-noise ratio (SNR) and relatively
      reduced sensitivity to physiological motion (e.g., brain pulsations) with respect
      to cardiac-gated multislice acquisition are demonstrated. The advantages and
      weaknesses of this approach are discussed.

PMID- 11979562
TI  - Rapid cine MRI of the human heart using reconstruction by estimation of lines and
      inhibition of fold-in.
AB  - A fast imaging method is described that yields an approximately six-fold
      acquisition time reduction relative to conventional techniques. The method
      involves: 1) acquisition of every sixth k-space line; 2) shifting of acquired k
      space lines between odd and even frames; and 3) a single-frame correction image.
      Reconstruction is achieved by temporal interpolation for k-space lines not
      acquired combined with subtraction of stationary fold-in artifacts. Seven
      patients with heart disease and one volunteer were evaluated. SNR was measured in
      myocardium and the ventricular cavity for both the conventional and new
      technique. The method is best suited for fast imaging of moving objects confined
      to a small region within a larger stationary object, such as the heart within the
      thoracic cavity. It can be implemented in cine and functional imaging sequences
      and, in principle, in perfusion sequences.

PMID- 11979563
TI  - Four-angle saturation transfer (FAST) method for measuring creatine kinase
      reaction rates in vivo.
AB  - A new fast method of measuring kinetic reaction rates for two-site chemical
      exchange is described. The method employs saturation transfer magnetic resonance
      spectroscopy (MRS) and acquisition of only four spectra under partially
      saturated, high signal-to-noise ratio (SNR) conditions. In two acquisitions one
      of the exchanging species is saturated; the other two employ a control
      saturation. Each pair of acquisitions is applied with two different flip angles,
      and the equilibrium magnetization, relaxation times, and reaction rates are
      calculated therefrom. This four-angle saturation transfer (FAST) method is
      validated theoretically using the Bloch equations modified for two-state chemical
      exchange. Potential errors in the rate measurements due to the effects of
      exchange are evaluated for creatine kinase (CK) metabolism modeled for skeletal
      and heart muscle, and are found to be < 5% for forward CK flux rates of 0.05 < or
      = k(f) < or = 1.0 s(-1), and up to a 90% depletion of phosphocreatine (PCr). The
      effect of too much or too little saturating irradiation on FAST appears to be
      comparable to that of the conventional saturation transfer method, although the
      relative performance deteriorates when spillover irradiation cuts the PCr signal
      by 50% or more. "FASTer" and " FASTest" protocols are introduced for dynamic CK
      studies wherein [PCr] and/or k(f) changes. These protocols permit the omission of
      one or two of the four acquisitions in repeat experiments, and the missing
      information is recreated from initial data via a new iterative algorithm. The
      FAST method is validated empirically in phosphorus ((31)P) MRS studies of human
      calf muscle at 1.5 T. FAST measurements of 10 normal volunteers yielded the same
      CK reaction rates measured by the conventional method (0.29 +/- 0.06 s(-1)) in
      the same subjects, but an average of seven times faster. Application of the
      FASTer algorithm to these data correctly restored missing information within
      seven iterations. Finally, the FAST method was combined with 1D spatially
      localized (31)P MRS in a study of six volunteers, yielding the same k(f) values
      independent of depth, in total acquisition times of 17-39 min. These timesaving
      FAST methods are enabling because they permit localized measurements of metabolic
      flux, which were previously impractical due to intolerably long scan times.

PMID- 11979564
TI  - Differential fMRI-BOLD signal response to apnea in humans and anesthetized rats.
AB  - Blood oxygenation level dependent (BOLD) signal intensity (SI) and regional
      cerebral blood flow (CBF) during a 20-s apnea stimulus in awake humans and
      pentobarbital-anesthetized rats were measured to assess the usefulness of apnea
      in estimating cerebral vasodilatory capacity for functional MRI (fMRI)
      experiments. Rats were ventilated with either room air or 100% O(2.) While
      breathing room air, apnea for 20 s increased the BOLD SI in humans but decreased
      it in rats. However, in rats ventilated with 100% O(2), BOLD SI increased upon
      apnea for 20 s. CBF measurements in rats using laser Doppler flowmetry (LDF)
      showed a 45% +/- 8% increase during apnea with room air ventilation, and a 10% +/
      3% increase with 100% O(2). Arterial blood oxygen saturation fell from 96% +/-
      1% to 29% +/- 5%, and cerebral tissue PO(2) decreased from 15 +/- 3 mmHg to 6 +/-
      2 mmHg by the end of 20-s apnea in rats breathing room air. However, with 100%
      O(2) respiration, apnea produced no change in the arterial blood oxygen
      saturation, which remained at 99%, but increased tissue PO(2) from 35 +/- 9 mmHg
      to 39 +/- 10 mmHg. From the results obtained in rats ventilated with room air, it
      is concluded that apnea induces hypoxia that results in a decrease in fMRI-BOLD
      signal. The signal decrease occurred despite an increase in P(a)CO(2) and CBF.
      This BOLD response is the opposite of that observed in humans, who presumably do
      not develop hypoxia within the applied apnea period. These studies highlight the
      importance of the choice of ventilating gas mixture on the outcome of BOLD
      experiments during systemic perturbations.

PMID- 11979565
TI  - Mapping the absolute value of M0 using dipolar field effects.
AB  - The ability to map the spatial variation of the absolute, rather than the
      relative value of the equilibrium magnetization could be advantageous in many
      areas of NMR. However, direct measurement of M(0) is usually difficult because of
      the multiparametric dependence of the NMR signal. Here we propose a technique for
      mapping the spatial variation of the absolute value of M(0), independent of
      relaxation weighting and flip angle calibration. This method, which works best at
      high field strengths, is based on the effect of the dipolar field due to the
      nuclear magnetization that is normally neglected in liquid-state NMR. The
      experimental implementation of this sequence at 3.0 T is described, and its
      initial application to the measurement of the water content of brain tissue is
      outlined.

PMID- 11979566
TI  - Proton magnetization transfer effect in rat liver lactate.
AB  - Off-resonance lactate magnetization transfer (MT) experiments were performed on
      the in situ rat liver under perfused and ischemic conditions. A significant MT
      effect for lactate methyl protons was observed. The effect was larger for the
      ischemic condition than for the perfused condition, and was largest in the blood
      filled ischemic livers. The size of the motionally restricted lactate pool,
      determined using a two-pool model fit, was estimated to be about 1% in perfused
      livers and about 1.8-2.5% after more than 1 hr of onset of ischemia, suggesting
      that lactate in liver is almost fully NMR-visible. The MT data for both the
      perfused and the ischemic condition appeared to be better approximated when
      assuming a superLorentzian lineshape for the immobile pool rather than a Gaussian
      lineshape. Finally, the experiments demonstrated a coupling between the lactate
      methyl and water protons, which may be mediated by macromolecules.

PMID- 11979567
TI  - Respiration-induced B0 fluctuations and their spatial distribution in the human
      brain at 7 Tesla.
AB  - In functional magnetic resonance imaging (fMRI), it is known that physiological
      influences such as cardiac pulsation, respiration, and brain motion can induce
      fluctuations in signal intensity and phase. Some of the mechanisms potentially
      involved in those phenomena are expected to be amplified at higher magnetic
      fields. This study addresses the issue of B(0) fluctuations induced by
      susceptibility changes during respiration attributed to movements of chest and
      diaphragm, and variations in the oxygen concentration. It is demonstrated that
      respiration-induced resonance offsets (RIROs) are significant at 7T. Data were
      acquired with an RF pulse (no gradients), multislice echo-planar imaging (EPI),
      and dynamic 3D fast low-angle shot (3D- FLASH) imaging. Three main observations
      summarize the experimental findings. First, in FIDs measured after a single RF
      pulse, a RIRO with a large amplitude was consistently detected, although the
      average amplitude varied between subjects from 1.45 Hz to 4 Hz. Second, in
      transverse EPI images obtained in the occipital lobe, the RIRO amplitude showed a
      monotonic increase along the z axis toward the lungs. Third, a more detailed
      spatial analysis with 3D-FLASH phase maps revealed that a previously published
      analytical model can accurately describe the spatial distribution of RIRO.
      Consequential apparent motions in the EPI series, as well as the implications of
      slice orientation for correction strategies are discussed.

PMID- 11979568
TI  - Blood pool contrast-enhanced MRI detects suppression of microvascular
      permeability in early postinfarction reperfusion after nicorandil therapy.
AB  - Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with a
      nitrate-like effect. It is approved for clinical use in Europe and Japan as an
      antianginal drug. The purpose of this investigation was to assess the acute
      effects of nicorandil therapy on microvascular injury using the blood pool MR
      contrast medium, NC100150 injection (Clariscan). Microvascular injury was
      produced in 24 rats using 45 min of coronary occlusion / 3 hr reperfusion.
      Nicorandil was infused at 15 min of occlusion and during reperfusion. Control
      animals received a saline solution. MR imaging was used to characterize
      microvascular permeability, quantify the extent of microvascular injury, LV
      volume, and wall thickness. Hyperenhancement at 30 min after administration of
      0.05 mmol/kg Clariscan mapped the extent of ischemia-induced loss of
      microvascular integrity. The accumulation of Clariscan in the injured region was
      significantly suppressed in nicorandil compared to control rats. Nicorandil
      reduced the extent of microvascular injury from 44 +/- 2% to 18 +/- 2% (P < 0.01)
      and true infarction size from 29 +/- 2% to 12 +/- 1%. The extent of the
      hyperenhanced region correlated with the true size of area at risk at autopsy. On
      spin-echo MRI during end-diastole, nicorandil reduced LV end-diastolic volume and
      preserved wall thickness in remote myocardium; both parameters are markers of LV
      dilatation caused by acute infarction (remodeling). In conclusion, blood pool
      contrast-enhanced MRI has the potential to depict and quantify the extent of
      microvascular permeability and injury. Nicorandil suppressed microvascular
      permeability, reduced infarction size, and improved LV function in early
      postinfarction reperfusion.

PMID- 11979569
TI  - Perfusion-based high-resolution functional imaging in the human brain at 7 Tesla.
AB  - Perfusion-based MRI measures cerebral blood flow (CBF) at the capillary level and
      can be used for functional studies based on the tight spatial coupling between
      brain activity and blood flow. Obtaining functional CBF maps with high spatial
      resolution is a major challenge because the CBF signal is intrinsically low and
      the SNR is critical. In the present work, CBF-based functional imaging was
      performed at a considerably smaller voxel size than previously reported in
      humans. High-resolution CBF maps were obtained with voxel sizes as small as 0.9 x
      0.9 x 1.5 mm(3) in the human brain. High sensitivity was made possible by signal
      to-noise gains at the high magnetic field of 7 T and by using a novel RF
      combination coil design. In addition, a reduction of the field-of-view was
      critical to achieve 0.9-mm in-plane resolution with gradient-echo echo-planar
      imaging in a single shot. Functional CBF data were compared with functional BOLD
      data to reveal that, for CBF, large contrast- to-noise gains were obtained at
      high spatial resolution, indicating that the functional CBF response was more
      localized. High-resolution functional CBF imaging is significant for neuroscience
      research because it provides better localization and more specific information
      than BOLD for monitoring brain function.

PMID- 11979570
TI  - Quantitative MRI assessment of leukoencephalopathy.
AB  - Quantitative MRI assessment of leukoencephalopathy is difficult because the MRI
      properties of leukoencephalopathy significantly overlap those of normal tissue.
      This report describes the use of an automated procedure for longitudinal
      measurement of tissue volume and relaxation times to quantify
      leukoencephalopathy. Images derived by using this procedure in patients
      undergoing therapy for acute lymphoblastic leukemia (ALL) are presented. Five
      examinations from each of five volunteers (25 examinations) were used to test the
      reproducibility of quantitated baseline and subsequent, normal-appearing images;
      the coefficients of variation were less than 2% for gray and white matter.
      Regions of leukoencephalopathy in patients were assessed by comparison with
      manual segmentation. Two radiologists manually segmented images from 15 randomly
      chosen MRI examinations that exhibited leukoencephalopathy. Kappa analyses showed
      that the two radiologists' interpretations were concordant (kappa = 0.70) and
      that each radiologist's interpretations agreed with the results of the automated
      procedure (kappa = 0.57 and 0.55). The clinical application of this method was
      illustrated by analysis of images from sequential MR examinations of two patients
      who developed leukoencephalopathy during treatment for ALL. The ultimate goal is
      to use these quantitative MR imaging measures to better understand therapy
      induced neurotoxicity, which can be limited or even reversed with some
      combination of therapy adjustments and pharmacological and neurobehavioral
      interventions.

PMID- 11979571
TI  - Test-retest reproducibility of quantitative CBF measurements using FAIR perfusion
      MRI and acetazolamide challenge.
AB  - The reproducibility of quantitative cerebral blood flow (CBF) measurements using
      MRI with arterial spin labeling and acetazolamide challenge was assessed in 12
      normal subjects, each undergoing the identical experimental procedure on two
      separate days. CBF was measured on a 1.5T scanner using a flow-sensitive
      alternating inversion recovery (FAIR) pulse sequence, performed both at baseline
      and 12 min after intravenous administration of acetazolamide. T(1) was measured
      in conjunction with the FAIR scan in order to calculate quantitative CBF. The CBF
      maps were segmented to separate gray matter (GM) from white matter (WM) for
      region-of-interest (ROI) analyses. Post- acetazolamide CBF values (ml/100 g/min,
      mean +/- SD) of 87.5 +/- 12.5 (GM) and 46.1 +/- 10.8 (WM) represented percent
      increases of 37.7% +/- 24.4% (GM) and 40.1% +/- 24.4% (WM). Day-to-day
      differences in baseline CBF were -1.7 +/- 6.9 (GM) and -1.4 +/- 4.7 (WM) or,
      relative to the mean CBF over both days for each subject, -2.5% +/- 11.7% (GM)
      and -3.8% +/- 13.6% (WM) Day- to-day differences in absolute post-ACZ CBF
      increase were -2.5 +/- 6.8 (GM) and 2.7 +/- 9.4 (WM) or, relative to the mean CBF
      increase over both days for each subject, -4.7% +/- 13.3% (GM) and 9.1% +/- 26.2%
      (WM). Thus, FAIR- based CBF measurements show satisfactory reproducibility from
      day to day, but with sufficient variation to warrant caution in interpreting
      longitudinal data. The hemispheric asymmetry of baseline CBF and post
      acetazolamide CBF increases varied within a narrower range and should be
      sensitive to small changes related to disease or treatment.

PMID- 11979572
TI  - Pulsed Z-spectroscopic imaging of cross-relaxation parameters in tissues for
      human MRI: theory and clinical applications.
AB  - A new method of pulsed Z-spectroscopic imaging is proposed for in vivo
      visualization and quantification of the parameters describing cross-relaxation
      between protons with liquid-like and solid-like relaxation properties in tissues.
      The method is based on analysis of the magnetization transfer (MT) effect as a
      function of the offset frequency and amplitude of a pulsed off- resonance
      saturation incorporated in a spoiled gradient-echo MRI pulse sequence. The
      theoretical concept of the method relies on an approximated analytical model of
      pulsed MT that provides a simple three-parameter equation for a pulsed steady
      state Z-spectrum taken far from resonance. Using this model, the parametric
      images of cross-relaxation rate constant, content, and T(2) of the semisolid
      proton fraction can be reconstructed from a series of MT-weighted images and a
      coregistered T(1) map. The method was implemented on a 0.5 T clinical MRI
      scanner, and it provided high-quality 3D parametric maps within an acceptable
      scanning time. The estimates of cross-relaxation parameters in brain tissues were
      shown to be quantitatively consistent with the literature data. Clinical examples
      of the parametric images of human brain pathologies (multiple sclerosis and
      glioma) demonstrated high tissue contrast and clear visualization of the lesions.

PMID- 11979573
TI  - MR temperature measurement in liver tissue at 0.23 T with a steady-state free
      precession sequence.
AB  - MRI can be used for monitoring temperature during a thermocoagulation treatment
      of tumors. The aim of this study was to demonstrate the suitability of a 3D
      steady-state free precession sequence (3D Fast Imaging with Steady-State
      Precession, 3D TrueFISP) for MR temperature measurement at 0.23 T, and to compare
      it to the spin-echo (SE) and spoiled 3D gradient-echo (3D GRE) sequences. The
      optimal flip angle for the TrueFISP sequence was calculated for the best
      temperature sensitivity in the image signal from liver tissue, and verified from
      the images acquired during the thermocoagulation of excised pig liver. Factors
      influencing the accuracy of the measured temperatures are discussed. The TrueFISP
      results are compared to the calculated values of optimized SE and 3D GRE
      sequences. The accuracy of TrueFISP in the liver at 0.23 T, in imaging conditions
      used during thermocoagulation procedures, is estimated to be +/-3.3 degrees C for
      a voxel of 2.5 x 2.5 x 6 mm(3) and acquisition time of 18 s. For the SE and GRE
      sequences, with similar resolution and somewhat longer imaging time, the
      uncertainty in the temperature is estimated to be larger by a factor of 2 and
      1.2, respectively.

PMID- 11979574
TI  - Subvoxel processing: a method for reducing partial volume blurring with
      application to in vivo MR images of trabecular bone.
AB  - Partial volume blurring precludes accurate measurement of structural dimensions
      in the limited-resolution regime in which image voxel size is larger than the
      typical structural element to be resolved. Since acquiring images at increased
      resolution often exacts an unacceptable signal-to-noise ratio (SNR) penalty,
      methods to alleviate the adverse effects of partial volume blurring are
      instrumental for the accurate measurement of architectural parameters in
      applications such as predicting the mechanical competence of trabecular bone
      networks. In the current work, a novel post-processing method, referred to as
      "subvoxel processing," is described for increasing apparent image resolution. The
      method is applicable to volumes of interest containing material phases of two
      discrete signal intensities. The principal strategy consists of subdividing
      voxels and assigning voxel intensities to each subvoxel on the basis of local
      neighborhood criteria and strict mass conservation. In the current work, the
      method's accuracy has been evaluated using microcomputed tomography images (22 x
      22 x 22 microm(3) voxel size) of human trabecular bone. The results demonstrate
      that subvoxel processing is significantly more accurate than trilinear
      interpolation in decreasing apparent voxel size, especially in the presence of
      noise. In addition, the method's effectiveness is illustrated with MR images of
      human trabecular bone acquired in vivo at 137 x 137 x 350 microm(3) voxel size.
      The subvoxel-processed images are shown to have architectural features
      characteristic of images acquired at higher spatial resolution.

PMID- 11979575
TI  - Cerebral oxygen extraction fraction and cerebral venous blood volume measurements
      using MRI: effects of magnetic field variation.
AB  - The presence of magnetic background field inhomogeneity (DeltaB) may confound
      quantitative measures of cerebral venous blood volume (vCBV) and cerebral oxygen
      extraction fraction (MR_OEF) with T2*-based methods. The goal of this study was
      to correct its effect and obtain more accurate estimates of vCBV and MR_OEF. A 3D
      high-resolution gradient echo sequence was employed to obtain DeltaB maps by two
      algorithms. The DeltaB maps were then used to recover the signal loss in images
      acquired by a 2D multiecho gradient echo / spin echo sequence. Finally, both
      quantitative estimates of MR_OEF and vCBV were obtained from the DeltaB-
      corrected 2D multiecho gradient echo / spin echo images. A total of 12 normal
      subjects were studied. An overestimated vCBV was observed in the brain (4.29 +/-
      0.78%) prior to DeltaB correction, while the measured vCBV was substantially
      reduced after DeltaB correction. Whole brain vCBV of 2.97 +/- 0.44% and 2.68 +/-
      0.47% were obtained by the two different DeltaB correction methods, in excellent
      agreement with the reported results in the literature. Furthermore, when MR_OEF
      was compared with and without DeltaB correction, no significant differences (P =
      0.467) were observed. The ability to simultaneously obtain vCBV and MR_OEF
      noninvasively may have profound clinical implications for the studies of
      cerebrovascular disease.

PMID- 11979576
TI  - White matter mapping using diffusion tensor MRI.
AB  - Diffusion tensor MRI is used to define trajectories that reflect the long-range
      order of in vivo white matter (WM) fiber tracts. Fiber tracking is particularly
      prone to cumulative error from noise and partial volume along the length of the
      trajectory paths, but the overall shape of each path is anatomically meaningful.
      By considering only the long-range similarity of path shapes, a method of
      constructing 3D maps of specific WM structures has been developed. A trajectory
      is first computed from an operator-selected seed voxel, located within the
      anatomical structure of interest (SOI). Voxels from the same structure are then
      automatically identified based on the similarity of trajectory path shapes,
      assessed using Pearson's correlation coefficient. The corpus callosum and
      pyramidal tracts in 14 patients with multiple sclerosis, and in 10 healthy
      controls were mapped by this method, and the apparent diffusion coefficient (ADC)
      was measured. The ADC was significantly higher in patients than in controls, and
      higher in the corpus callosum than in the pyramidal tracts for both groups. Using
      this method the different functional structures in the WM may be identified and
      mapped. Within these maps, MRI parameters can be measured for subsequent
      comparison with relevant clinical data.

PMID- 11979577
TI  - Evaluation of four postprocessing methods for determination of cerebral blood
      volume and mean transit time by dynamic susceptibility contrast imaging.
AB  - Four different postprocessing methods to determine cerebral blood volume (CBV)
      and contrast agent mean transit time (MTT) by dynamic susceptibility contrast
      (DSC) MRI were compared. CBV was determined by two different methods that
      integrate tracer concentration-time curves numerically and by two other methods
      that take recirculation into account. For the two methods that use numerical
      integration, one method cuts the integration after the first pass while the other
      method integrates over the whole time series. For the two methods that account
      for recirculation, one method uses a gamma-variate fit, whereas the other method
      utilizes tissue impulse response. All four methods determine MTT as the ratio of
      CBV and cerebral blood flow (CBF). In each case, CBF was obtained as the height
      of the impulse response obtained by deconvolving the tissue concentration-time
      curves with a noninvasively determined arterial input function. Monte Carlo
      simulations were performed to determine the reliability of the methods and the
      validity of the simulations was supported by observation of similar trends in 13
      acute stroke patients. The method of determining CBV and subsequently MTT was
      found to affect the measured value especially in areas where MTT is prolonged,
      but had no apparent effect on the visually determined hypoperfusion volumes.

PMID- 11979578
TI  - Analysis of wave behavior in lossy dielectric samples at high field.
AB  - Radiofrequency (RF) field wave behavior and associated nonuniform image intensity
      at high magnetic field strengths are examined experimentally and numerically. The
      RF field produced by a 10-cm-diameter surface coil at 300 MHz is evaluated in a
      16-cm-diameter spherical phantom with variable salinity, and in the human head.
      Temporal progression of the RF field indicates that the standing wave and
      associated dielectric resonance occurring in a pure water phantom near 300 MHz is
      greatly dampened in the human head due to the strong decay of the electromagnetic
      wave. The characteristic image intensity distribution in the human head is the
      result of spatial phase distribution and amplitude modulation by the interference
      of the RF traveling waves determined by a given sample-coil configuration. The
      numerical calculation method is validated with experimental results. The general
      behavior of the RF field with respect to the average brain electrical properties
      in a frequency range of 42-350 MHz is also analyzed.

PMID- 11979579
TI  - Detunable transverse electromagnetic (TEM) volume coil for high-field NMR.
AB  - Most high-field MRI systems do not have the actively detuned body coils that are
      integral to clinical systems operating at 1.5T and lower field strengths.
      Therefore, many clinical applications requiring homogeneous volume excitation in
      combination with local surface coil reception are not easily implemented at high
      fields. To solve this problem for neuroimaging applications, actively detunable
      transverse electromagnetic (TEM) head coils were developed to be used with
      receive-only surface coils for signal-to-noise ratio (SNR) gains and improved
      spatial coverage from homogeneously excited regions. These SNR and field of view
      (FOV) gains were achieved by application of a detunable TEM volume coil to human
      brain imaging at 4T.

PMID- 11979580
TI  - Noninvasive in vivo oximetric imaging by radiofrequency FT EPR.
AB  - A novel method, called relaxo-oximetry, for rapid spatially resolved in vivo
      measurements of oxygen concentration using time-domain radiofrequency (RF)
      electron paramagnetic resonance (EPR) is described. Time-domain data from triaryl
      methyl (TAM)-based single-electron contrast agents were processed by systematic
      deletion of the initial time points to arrive at T2*-weighted discrimination of
      signal amplitudes. In experiments involving phantoms, the line widths [
      approximately (T2*)(-1)] increased as a function of oxygen, and the slope (line
      width/pO(2)) was the same for both absorption- and magnitude-mode line shapes.
      Line widths derived from T2* weighting and the computed pO(2) values agreed
      favorably with the measured ones from phantoms of known oxygen tension. In vivo
      relaxo-oximetry was performed on C3H mice, and it was found that the liver was
      more hypoxic than the kidneys. For tumors, 2D oxygen maps were generated while
      the animal breathed room air or Carbogen(R) (95% O(2)/5% CO(2)). Carbogen(R)
      enhanced oxygen concentration within the tumor, and the pO(2) histograms showed
      considerable heterogeneity. Clark electrode oxygen measurements on organs and
      tumors were in good agreement with tissue oxygen measurements done by relaxo
      oximetry. Thus, from a single spatial image data set, pO(2) measurements can be
      done noninvasively by relaxo-oximetry, and 3D imaging can be performed in less
      than 3 min.

PMID- 11979581
TI  - Direct in vivo measurement of human cerebral GABA concentration using MEGA
      editing at 7 Tesla.
AB  - Spectral editing of the GABA spin system is hampered by coediting of
      macromolecule (MM) coherences. To reduce contamination arising from MMs in
      spectra edited for GABA, the highest field strength currently available for human
      experimentation (7 Tesla) and MEGA-based editing were used. Despite judicious
      choice of experimental parameters, MM contamination was found to arise from field
      drifts. When the MM contribution was accounted for, [GABA] = 0.75 +/- 0.14
      micromol/g (mean +/- SD, N = 16) relative to 8 micromol/g creatine (Cr), whereas
      without accounting for the MM signal [GABA*] = 0.88 +/- 0.23 micromol/g (mean +/-
      SD, N = 16). Incorporating the direct experimental assessment of MM contamination
      to the edited GABA signal substantially reduced the variance of the measurement,
      resulting in concentrations that were in excellent agreement with previous (13)C
      labeling experiments.

PMID- 11979582
TI  - Determination of regional blood volume and intra-extracapillary water exchange in
      human myocardium using Feruglose: First clinical results in patients with
      coronary artery disease.
AB  - The aim of this pilot study in humans was to investigate the effect of an
      intravascular contrast agent (CA) on relaxation rate in myocardium (R(1,myo)) in
      the steady state. The dependence of R(1,myo) on R(1,blood) was characterized and
      compared with a theoretical model which allowed determination of the intra-
      extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the
      intracapillary blood volume (RBV = 12.9 %). A linear response range of
      DeltaR(1,myo) on DeltaR(1,blood) was estimated which in future studies will allow
      the determination of RBV with intravascular CA.

PMID- 11979583
TI  - Improved efficiency in double-inversion fast spin-echo imaging.
AB  - Double-inversion fast spin-echo (FSE) pulse sequences can be designed to provide
      excellent suppression of blood signal in black-blood MRI. However, because a
      nonselective inversion is used, these sequences typically have been highly
      inefficient. In this work it is demonstrated that the efficiency of double
      inversion sequences can be greatly improved by a form of interleaving in which
      all of the slices to be imaged in a single pass are reinverted each time a signal
      is obtained from any single slice. To date, several studies have demonstrated a
      high level of blood suppression with these more efficient techniques.

PMID- 11979584
TI  - New approach to 3D time-resolved angiography.
AB  - TRICKS is an acquisition and reconstruction method capable of generating 3D time
      resolved angiograms. Arguably, the main problem with TRICKS is the way it handles
      the outer regions of the k-space matrix, leading to artifacts at the edges of
      blood vessels. An alternative to the data- processing stage of TRICKS, designed
      to better represent edges and small vessels, is presented here. A weakness of the
      new approach is an increased sensitivity to motion compared to TRICKS. Since this
      method can use the same data as TRICKS, a hybrid reconstruction method could
      conceivably be developed where the advantages of both approaches are combined.
      Magn Reson Med 47:1022-1025, 2002.

PMID- 11979585
TI  - Different excitation and reception distributions with a single-loop transmit
      receive surface coil near a head-sized spherical phantom at 300 MHz.
AB  - Calculations and experiments were used to examine the B(1) field behavior and
      signal intensity distribution in a 16-cm diameter spherical phantom excited by a
      10-cm diameter surface coil at 300 MHz. In this simple system at this high
      frequency very complex RF field behavior exists, resulting in different
      excitation and reception distributions. Included in this work is a
      straightforward demonstration that coil receptivity is proportional to the
      magnitude of the circularly polarized component of the B(1) field that rotates in
      the direction opposite to that of nuclear precession. It is clearly apparent that
      even in very simple systems in head-sized samples at this frequency it is
      important to consider the separate excitation and reception distributions in
      order to understand the signal intensity distribution.

PMID- 11979586
TI  - Toxicity of different industrial effluents in Taiwan: a comparison of the
      sensitivity of Daphnia similis and Microtox.
AB  - Industrial effluents are known to exhibit toxicity toward different aquatic
      organisms. In Taiwan management of these discharges still relies on chemical and
      physical and physical characteristics of water, although various standard method
      for assessing aquatic toxicity have been proposed by the Taiwan Environmental
      Protection Administration. In this study we examined the toxicity and compared
      the sensitivity of different types of industrial effluents using two proposed
      toxicity tests: the Daphnia similis acute toxicity test and the Microtox acute
      assay (Vibrio fischeri). Results showed that electroplating effluents were the
      most toxic of all the effluents tested, followed by acrylonitrile manufacturing,
      pulp/paper, and tannery effluents. The EC50 of an electroplating effluent for D.
      similis and V. fischeri (15 min) was as low as, respectively, 2.9% and 3.9% of
      the whole effluent. The other effluents were not acutely toxic to either organism
      tested. However, the tests exhibited different sensitivity toward various
      discharges. Only the electroplating and acrylonitrile manufacturing effluents had
      effects on both organisms. These results indicate the importance of the
      incorporation of aquatic toxicity tests into the management scheme for treated
      wastewaters.

PMID- 11979587
TI  - Using scanning electron microscopy for statistical characterization of the
      diameter and shape of airborne particles at an urban location.
AB  - Particles in the air are characterized not only by their effective diameters but
      by their shapes as well. In this study electron microscopy was used to provide
      detailed information about individual particles, including diameter and shape.
      Following image analysis, statistical methods were used to describe diameter and
      shape distribution. From using this technique for repeated measuring at a
      particular location an interesting finding was made: the diameter and shape
      factor distributions had a constant nature.

PMID- 11979588
TI  - Estrogenic effect of leachates and soil extracts from lysimeters spiked with
      sewage sludge and reference endocrine disrupters.
AB  - Several experiments were conducted to evaluate the behavior and performance of
      some potential endocrine disrupters (ECDs). Two in vitro screening assays, one
      based on MCF7-cell proliferation (E-screen test) and the other on estrogenic
      receptor activity [enzyme-linked receptor assay (ELRA)], were used for the tests,
      which were done in lysimeters 80 cm in diameter with depth of 30 cm (shallow) or
      90 cm (deep). A sandy soil was used to fill in all lysimeters, which were spiked
      on the surface with either: (a) a sewage sludge (SS) at a dose equivalent to 20
      tons ha-1; (b) a mixture of reference ECDs, comprising 17 alpha- and 17 beta
      estradiol (E2), nonylphenol, octylphenol, and bisphenol A at doses 100 times
      higher than the maximum concentrations respectively found in the applied SS; or
      (c) a mixture of ECDs and SS. After percolation of the lysimeters with rain
      and/or artificial water, five leachates were sampled from each lysimeter during a
      period of 210 days. Immediately after the lysimeter percolation experiments, four
      and six soil fractions were dissected from, respectively, the 30-cm and 90-cm
      lysimeters and extracted by water. Both the leachate and soil extract samples
      were analyzed for their estrogenicity using the assays indicated above. The E
      screen assay was highly sensitive only for some leachate and extract samples but
      gave no response for most leachates and soil extracts. The results of the ELRA
      assay suggests a significantly higher estrogenicity of leachate samples from
      shallow lysimeters compared with that of leachates from deep lysimeters. In
      contrast, the estrogenic effect measured for soil extracts of shallow lysimeters
      was lower than that measured for soil extracts of deep lysimeters. The results of
      the E-screen assay suggests the occurrence of a fast mobilization of applied ECDs
      and a moderate retardation effect of native ECDs contained in applied SS in the
      sandy soil used in the lysimeters. In lysimeters spiked with a mixture of SS and
      ECDs, the washing-out effect of ECDs in the first leachate fraction decreased,
      but the distribution of ECDs in the lysimeters increased. The relatively high
      estrogenic impact measured for soil water extracts suggests that the ECDs were
      mostly associated with water-soluble fractions of organic matter and/or water
      suspended fractions of the mineral soil matrix. The application of SS to
      agricultural and forest fields may determine the immobilization of ECDs in soil
      or their movement to surface and/or groundwater. Therefore, an endocrine risk of
      exposure exists for the water and soil organisms.

PMID- 11979589
TI  - Variation in toxin compositions of two harmful raphidophytes, Chattonella antiqua
      and Chattonella marina, at different salinities.
AB  - Toxin compositions of the two species of raphidophytes, Chattonella antiqua
      (Hada) Ono and Chattonella marina (Subrahmanyan) Hara et Chihara, were
      investigated at different salinities under laboratory conditions. C. antiqua
      contained toxin components CaTx-I, CaTx-II, CaTx-III, and CaTx-IV, which
      corresponded to brevetoxin components PbTx-1, PbTx-2, PbTx-3, and oxidized PbTx
      2. Similarly, C. marina included CmTx-I, CmTx-II, CmTx-III, and CmTx-IV
      corresponding to PbTx-2, PbTx-9, PbTx-3, and oxidized PbTx-2. Toxin yields in
      both species varied markedly with a change in salinity concentration. In C.
      antiqua CaTx-I, CaTx-II, and CaTx-III peaked at 25 P.P.t. with yields of 0.99,
      0.42, and 2.90 pg/cell, but the highest yield (2.35 pg/cell) of CaTx-IV was
      attained at 30 P.P.t. The yields of all CaTx components decreased sharply at
      salinities exceeding 30 P.P.t. On the other hand, C. marina yielded higher
      proportions of CmTx-I (0.55 pg/cell) and CmTx-III (2.50 pg/cell) at 25 P.P.t.
      However, CmTx-IV was present in its highest amount (1.65 pg/cell) at 30 P.P.t.,
      as seen in C. antiqua. A small amount of CmTx-II was also detected at 20 P.P.t.
      35 P.P.t. Both species showed the highest ichthyotoxicities at 25 P.P.t., at
      which the maximum cell division rate was obtained.

PMID- 11979590
TI  - Determining the mechanisms of toxic action of phenols to Tetrahymena pyriformis.
AB  - Phenols are environmentally important compounds that are widely used in
      agriculture and industry. Thus, phenols are of interest to environmental
      toxicologists, which has led to the development of several quantitative structure
      activity relationship (QSAR) models. The most successful QSARs have been
      established for compounds having a common mechanism of toxic action (MOA).
      However, correctly determining the MOA of a compound is not easy. Discriminant
      analysis was used in this study to separate phenols by their MOAs. The working
      hypothesis of this study was that phenols with different MOAs lie in different
      regions in the response surface described by the ionization-corrected
      hydrophobicity descriptor, log D, the electrophilicity descriptor, ELUMO, and the
      interaction between hydrophobicity and electrophilicity, D * ELUMO. Results of
      discriminant analysis showed a total error rate of 15%. In addition, it was
      difficult to separate phenols that had a polar narcosis MOA from phenols that had
      a proelectrophile MOA.

PMID- 11979591
TI  - Relative potencies of individual polycyclic aromatic hydrocarbons to induce
      dioxinlike and estrogenic responses in three cell lines.
AB  - The dioxinlike and estrogenic relative potencies (REPs) of 16 priority polycyclic
      aromatic hydrocarbons (PAHs), seven methylated PAHs, and two hydroxylated PAHs
      were examined using three in vitro cell bioassays. An in vitro ethoxyresorufin-O
      deethylase assay with PLHC-1 fish hepatoma cells and in vitro luciferase assay
      with H4IIE-luc recombinant rat hepatoma cells were used to evaluate dioxinlike
      potency. An in vitro luciferase assay with MVLN, recombinant human breast
      carcinoma cells, was used to evaluate estrogenic potency. Seven of the 16
      priority PAHs tested induced significant dioxinlike responses. Excluding outliers
      with large ranges of uncertainty, the dioxinlike REPs for the PAHs ranged from
      10(-6) to 10(-3). This is similar to the REPs reported for other xenobiotics of
      concern including polychlorinated naphthalenes (PCNs) and some polychlorinated
      biphenyls (PCBs). In general, REP estimates generated in this study were similar
      to those reported previously. However, a comparison of the estimates of total
      2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents derived using assay-specific REPs
      with REPs reported in other studies indicated that the use of nonspecific REPs
      could lead to significant error in mass-balance (potency-balance) analyses. A 10
      h acid treatment completely destroyed the dioxinlike activity of a PAH mixture.
      Among the compounds tested, only benzo[a]anthracene and dibenz[a,h]anthracene
      induced significant responses in the MVLN bioassay. Relative estrogenic potencies
      were estimated to be approximately 10(-7). Overall, this research contributes to
      the growing consensus regarding the dioxinlike potency of priority PAHs and PAH
      derivatives and provides some additional evidence about potentially estrogenic
      PAHs.

PMID- 11979592
TI  - Reproductive potential of crimson-spotted rainbowfish (Melanotaenia fluviatilis)
      following short-term exposure to bass strait crude oil and dispersed crude oil.
AB  - An examination of the potential of crude oil and mixtures of dispersants and
      crude oil to act as reproductive toxicants is reported in this article. The short
      term effects of a water-accommodated fraction of crude oil (WAF) and a dispersed
      crude oil water-accommodated fraction (DCWAF) on selected reproductive end points
      were measured by conducting 3-day exposures to the crimson-spotted rainbowfish
      (Melanotaenia fluviatilis). Exposures were followed by 14-day depuration periods
      to determine the ability of fish to recover from the exposure. There were no
      changes to egg production, hatchability, or larval lengths for the WAF and DCWAF
      test periods. There were no changes to plasma estradiol or testosterone
      concentrations, gonadosomatic indices, or histopathological organization of gonad
      tissues after the exposure and depuration periods for both WAF and DCWAF. As
      reproductive parameters were not altered after 3 days of exposure and 14 days of
      depuration, crimson-spotted rainbowfish were able to endure short-term exposures
      to crude oil and dispersed crude oil.

PMID- 11979593
TI  - Time-resolved FTIR difference spectroscopy as tool for investigating refolding
      reactions of ribonuclease T1 synchronized with trans --> cis prolyl
      isomerization.
AB  - The structurally well-characterized enzyme ribonuclease T1 was used as a model
      protein to further evaluate time-resolved Fourier transform IR difference
      spectroscopy in conjunction with temperature-jump techniques as a useful
      detection technique for protein folding studies. Compared to the wild-type
      protein, it was confirmed that the lack of one cis-proline bond at position 55 of
      the S54G/P55N variant is sufficient to significantly simplify and accelerate the
      refolding process. This result was sustained by the characterization of the early
      refolding events that occurred within the experimental dead time.

PMID- 11979594
TI  - Resonance Raman spectroscopic studies in copper reconstituted and hybrid
      hemoglobins: probe into subunit heterogeneity.
AB  - Copper reconstituted hemoglobin (CuHb), copper containing T-state hybrid
      hemoglobins like alpha2(Ni)beta2(Cu), and alpha2(Cu)beta2(Ni), and intermediate R
      state hybrids like alpha2(CO-Fe)beta2(Cu) and alpha2(Cu)beta2(Fe-CO) are studied
      using resonance Raman (RR) spectroscopy at two different excitation wavelengths.
      The high frequency RR region in CuHb indicates the presence of both 4- and 5
      coordinate forms of Cu(II). In hybrid Hbs, the presence of two distinct metal ion
      environments within one particular subunit is evident. This is also consistent
      with previous findings using EPR spectroscopy and sulfydryl reactivity studies on
      these hybrid Hbs. The low frequency RR region on these copper derivatives of HbA
      further suggests the existence of two different heme moieties within the subunit.

PMID- 11979595
TI  - Receptor-dependent G-protein activation in lipidic cubic phase.
AB  - The primary step in cellular signaling by G-protein-coupled receptors (GPCRs) is
      the interaction of the agonist-activated transmembrane receptor with an
      intracellular G-protein. Understanding the underlying molecular mechanisms
      requires the structural determination of receptor G-protein complexes that are
      not yet achieved. The crystal structure of the bovine photoreceptor rhodopsin, a
      prototypical GPCR, was solved recently and the structures of different states of
      engineered G-proteins were reported. Posttranslational hydrophobic modifications
      of G-proteins are in most cases removed for crystallization but play functional
      roles for interactions among G-protein subunits with receptors, as well as
      membranes. Bovine rhodopsin is reconstituted into lipidic cubic phases to assess
      their potential for crystallization of receptor G-protein complexes under
      conditions that may preserve the structural and functional roles of hydrophobic
      protein modifications. Three-dimensional bilayers of a bicontinuous lipidic cubic
      phase are successfully employed for crystallization of membrane and soluble
      proteins. UV-visible absorption and attenuated total reflection Fourier transform
      IR difference spectroscopy reveal that light activation of cubic phase
      reconstituted rhodopsin results in the generation of a metarhodopsin II-like
      state. Via diffusion along aqueous channels, transducin couples efficiently to
      this photoproduct as evidenced by the nucleotide-dependent increase of transducin
      fluorescence. Thus, rhodopsin transducin interactions do not crucially depend on
      the presence of sn1 and sn2 acyl chains, phospholipid head groups, or membrane
      planarity. Because lipidic cubic phases preserve the essential functional and
      structural properties of native rhodopsin and transducin, they appear suitable
      for the detergent-free crystallization of receptor G-protein complexes carrying a
      normal pattern of hydrophobic modifications.

PMID- 11979596
TI  - Evidence for nonhydrogen bonded compound II in cyclic reaction of hemoglobin I
      from Lucina pectinata with hydrogen peroxide.
AB  - Studies that elucidate the behavior of the hemoglobins (Hbs) and myoglobins upon
      reaction with hydrogen peroxide are essential to the development of oxygen
      carrier substitutes. Stopped-flow kinetics and resonance Raman data show that the
      reaction between hydrogen peroxide and oxygenated and deoxygenated ferric Hb I
      (oxy- and deoxy-HbI) from Lucina pectinata produce compound I and compound II
      ferryl species. The rate constants ratio (k23/k41) between the formation of
      compound II from compound I (k23) and the oxidation of the ferrous HbI (k41,
      i.e., 25 M(-1) s(-1)) of 12 x 10(-4) M suggests that HbI has a peroxidative
      capacity for removing H2O2 from solution. Resonance Raman presents the formation
      of both, met-aquo-HbI and compound II ferryl species in the cyclic reaction of
      HbI with H2O2. The ferric HbI species is maintained by the presence of H2O2; it
      can produce HbI compound I, or it can be reduced to a deoxy-HbI derivative to
      form HbI compound II upon reaction with H2O2. The compound II ferryl vibration
      frequency appears at 805 and 769 cm(-1) for HbIFe(IV)=(16)O and HbIFe(IV)=(18)O
      species, respectively. This ferryl mode indicates the absence of hydrogen bonding
      between the carbonyl group of the distal Q64 and the HbIFe(IV)=O ferryl moiety.
      The observation suggests that both the trans-ligand effect and the polarizabilty
      of the HbI heme pocket are responsible for the observed ferryl oxo vibrational
      energy. The vibrational mode also suggests that the carbonyl group of the distal
      Q64 is oriented toward the iron of the heme group, increasing the distal pocket
      electron density.

PMID- 11979597
TI  - Binding modes of cyclic AMP and environments of tryptophan residues in 1:1 and
      1:2 complexes of cyclic AMP receptor protein and cyclic AMP.
AB  - Cyclic AMP (cAMP) receptor protein (CRP) forms 1:1 and 1:2 complexes with cAMP,
      and the former complex is considered to be the most active form of CRP in binding
      to specific DNA sequences and in modulating gene transcription by RNA
      polymerases. We examine the cAMP binding modes and structural changes of CRP upon
      cAMP binding by UV resonance Raman spectroscopy. The Raman spectra of CRP
      (cAMP)(1) and CRP-(cAMP)(2) extracted from those of CRP-cAMP mixtures at varied
      mixing ratios clearly show that the hydrogen bonding state and the conformation
      of cAMP in both complexes in solution are very similar to those found in the X
      ray crystal structure of CRP-(cAMP)(2), which is evidence that the cAMP binding
      mode does not differ between the two complexes. The environmental hydrophobicity
      of Trp85 monitored by UV resonance Raman intensity shows a significant decrease
      upon binding of the first cAMP molecule, whereas no further change occurs in the
      second cAMP binding step. The environmental change of Trp85 suggests an opening
      of the cleft between the N-terminal cAMP and C-terminal DNA binding domains in
      the process of CRP activation by binding of a single cAMP molecule.

PMID- 11979598
TI  - Protecting genetic difference.

PMID- 11979599
TI  - Maintaining incentives for bioprospecting: the occasional need for a right to
      lie.

PMID- 11979600
TI  - The dissection debate.

PMID- 11979601
TI  - HIV, women, and access to clinical trials: tort liability and lessons from DES.

PMID- 11979602
TI  - The case against mandatory HIV testing of pregnant women: the legal and public
      policy implications.

PMID- 11979603
TI  - The ethics of contact tracing programs and their implications for women.

PMID- 11979604
TI  - Piercing the veil of secrecy in HIV/AIDS and other sexually transmitted diseases:
      theories of privacy and disclosure in partner notification.

PMID- 11979605
TI  - Should genes be patented? The gene patenting controversy: legal, ethical, and
      policy foundations of an international agreement.

PMID- 11979606
TI  - My egg, your sperm, whose preembryo? A proposal for deciding which party receives
      custody of frozen preembryos.

PMID- 11979607
TI  - Multiple choice in baby making.

PMID- 11979608
TI  - [Eggs are now out of ban--images and real effects].

PMID- 11979609
TI  - [Does D-dimer help when blood coagulates?].

PMID- 11979610
TI  - [Nobel prize in physiology and medicine to Gunter Blobel].

PMID- 11979611
TI  - [A psychiatrist from 3rd Line--Matti Huttunen got the Kondrad Reijo Waara prize].

PMID- 11979612
TI  - [The Young Scientist award to Tapio Visakorpi].

PMID- 11979613
TI  - [Entacapone in the therapy of Parkinson disease].

PMID- 11979614
TI  - [Delayed sleep phase insomnia].

PMID- 11979615
TI  - [Using video conferences and telemedicine in orthopedic consultations].

PMID- 11979616
TI  - [Cutaneous and cerebral cryptococcosis during corticosteroid therapy].

PMID- 11979617
TI  - [Thyroid dysfunction and pregnancy].

PMID- 11979618
TI  - [Vomiting, nausea and episodic atrial fibrillation].

PMID- 11979619
TI  - [Sore throat and heaviness of chest in an elderly woman].

PMID- 11979620
TI  - [Trauma patients' urinary catheterization].

PMID- 11979621
TI  - [It is not sensible to decentralize surgical activities].

PMID- 11979622
TI  - [On the pharyngitis treatment guidelines].

PMID- 11979628
TI  - On the bleeding edge.

PMID- 11979629
TI  - Talking with Richard Aderman of Roche Laboratory Systems. Interview by C. Anne
      Pontius.

PMID- 11979630
TI  - What do you want from your reference laboratory? A report card on send-out
      testing in the Pacific northwest.

PMID- 11979631
TI  - What accommodations does a hearing-impaired patient require?

PMID- 11979632
TI  - From the traditional concept of safety management to safety integrated with
      quality.
AB  - This editorial reviews the evolution of the concepts of safety and quality that
      have been used in the traditional workplace. The traditional programs of safety
      are explored showing strengths and weaknesses. The concept of quality management
      is also viewed. Safety management and quality management principles, stages, and
      measurement are highlighted. The concepts of quality and safety guarantee are
      assessed. Total Quality Management concepts are reviewed and applied to safety
      quality. Total safety management principles are discussed. Finally, an analysis
      of the relationship between quality and safety from data collected from a company
      in Spain is presented.

PMID- 11979633
TI  - Effects of uncertainty, transmission type, driver age and gender on brake
      reaction and movement time.
AB  - PROBLEM: Braking time (BT) is a critical component in safe driving, and various
      approaches have been applied to minimize it. This study analyzed the components
      of BT in order to assess the effects of age, gender, vehicle transmission type,
      and event uncertainty, on its two primary components, perception-reaction time
      and brake-movement time. METHOD: Perception-reaction time and brake-movement time
      were measured at the onset of lights for 72 subjects in a simulator. The six
      experimental conditions were three levels of uncertainty conditions (none, some,
      and some + false alarms) and two types of transmission (manual and automatic).
      The 72 subjects, half male and half female, were further divided into three age
      groups (mean of 23, 30, and 62 years). Each subject had 10 trials in each of the
      three levels of uncertainty conditions. RESULTS: Transmission type did not
      significantly affect either perception-reaction time or brake-movement time.
      Perception-reaction time increased significantly from 0.32 to 0.42 s (P < .05) as
      uncertainty increased but brake-movement time did not change. Perception-reaction
      time increased (from 0.35 to 0.43 s) with age but brake-movement time did not
      change with age. Gender did not affect perception-reaction time but did affect
      brake-movement time (males 0.19 s vs. females 0.16 s). IMPACT ON INDUSTRY: At 90
      km/h, a car travels 0.25 m in 0.01 s. Consequently, even such small effects
      multiplied by millions of vehicle-kilometers can contribute to significant
      savings in lives and damages.

PMID- 11979634
TI  - Rate of occupational accidents in the mining industry since 1950--a successful
      approach to prevention policy.
AB  - This paper deals with the decrease in the rate of accident insurance claims in
      the German mining industry over the last five decades. It intends to show that
      this process is above all the result of a prevention policy where companies and
      the body responsible for the legal accident insurance in the mining industry, the
      Bergbau-Berufsgenossenschaft (BBG), work hand in hand. A system like the German
      accident insurance scheme, combining prevention, rehabilitation, and
      compensation, enables successful and modern safety and health measures.

PMID- 11979635
TI  - Safety teams. Government and business organizations want them and use them, but
      are they legal?
AB  - BACKGROUND: Safety teams have become a popular means to recognize and prevent
      injuries in the workplace. In fact, organizations, such as OSHA, NIOSH, NIEHS,
      DOE, and the Ohio BWC, not only encourage safety teams, but have implemented them
      in their organizations. However, safety teams may not be legal as defined by NLRB
      Act Sections 2(5) and 8(a)(2). OBJECTIVE: To determine whether safety teams are
      illegal labor organizations. METHODS: A review of government regulations, safety
      programs, and safety teams was performed to create a framework of what types of
      safety programs/regulations are requested and/or required by a variety of
      government agencies. Next, these requirements were compared to existing case law
      on illegal labor organizations as defined by the NLRB. RESULTS: Most safety teams
      and programs, even those implemented by the Federal Government, are illegal labor
      organizations as defined by NLRB Act Sections 2(5) and 8(a)(2). CONCLUSIONS: The
      Federal Government needs to amend existing legislation and develop a revision of
      the NLRB Act that would allow safety teams to function legally in organizations
      without having to meet intrusive, constricting guidelines that may inhibit the
      value of safety teams. IMPACT ON INDUSTRY: Organizations must be aware that
      safety teams may be valuable in reducing job-related accidents and injuries but
      they may be illegal labor organizations.

PMID- 11979636
TI  - Perceived safety climate, job demands, and coworker support among union and
      nonunion injured construction workers.
AB  - PROBLEM: This study evaluated injured construction workers' perceptions of
      workplace safety climate, psychological job demands, decision latitude, and
      coworker support, and the relationship of these variables to the injury severity
      sustained by the workers. METHODS: Injury severity was assessed using the Health
      Assessment Questionnaire (HAQ), which evaluates functional limitations. Worker
      perceptions of workplace variables were determined by two instruments: (a) the
      Safety Climate Measure for Construction Sites and (b) the Job Content
      Questionnaire (JCQ). RESULTS: The overall model explained 23% of the variance in
      injury severity, with unique contributions provided by union status, the Safety
      Climate Score, and Psychological Job Demands. A positive significant correlation
      was found between injury severity and the Safety Climate Scores (r = .183, P =
      .003), and between the Safety Climate Scores and union status (r = .225, P <
      .001). DISCUSSION: There were statistically significant differences between union
      and nonunion workers' responses regarding perceived safety climate on 5 of the 10
      safety climate items. Union workers were more likely than nonunion workers to:
      (a) perceive their supervisors as caring about their safety; (b) be made aware of
      dangerous work practices; (c) have received safety instructions when hired; (d)
      have regular job safety meetings; and (e) perceive that taking risks was not a
      part of their job. However, with regard to the 49-item JCQ, which includes
      Coworker Support, the responses between union and nonunion workers were very
      similar, indicating an overall high degree of job satisfaction. However, workers
      who experienced their workplace as more safe also perceived the level of
      management (r = -.55, P < .001) and coworker (r = -.31, P < .001) support as
      being higher. IMPACT ON INDUSTRY: The findings of this study underscore the
      critical need for construction managers to alert workers to dangerous work
      practices and conditions more frequently, and express concern and praise workers
      for safe work in a manner that is culturally acceptable in this industry.
      Workplace interventions that decrease the incidence and severity of injuries, but
      that are flexible enough to meet a variety of potentially competing imperatives,
      such as production deadlines and client demands, need to be identified.

PMID- 11979637
TI  - A survey of forest workers in New Zealand. Do hours of work, rest, and recovery
      play a role in accidents and injury?
AB  - PROBLEM: A number of structural and organizational changes have occurred recently
      within the New Zealand Forestry Industry, with concerns being raised about the
      impact of these changes on the forestry worker in terms of fatigue, sleepiness,
      and compromised safety. This study explored the relationship of fatigue, and some
      of its key determinants, with accidents and injuries in a group of forestry
      industry workers in New Zealand. METHOD: A total of 367 forestry workers
      responded to a self-administered questionnaire. RESULTS: Fatigue was found to be
      commonly experienced at work in the forest, with 78% of workers reporting that
      they experienced fatigue at least "sometimes." This study found that certain
      groups of workers reported long working hours, reduced sleep, compromised
      recovery time, and intensely paced work. The results of logistic regression
      analysis showed that recent sleep, number of breaks taken during the workday, and
      specific job/tasks were independently associated with reporting of high fatigue
      levels at work. Near-miss injury events were significantly more common among
      those reporting a high level of fatigue at work. Accidents and lost-time injury
      were associated with length of time at work, ethnicity, and having had near-miss
      injury events. DISCUSSION: Together, these results suggest that fatigue and
      aspects of work organization, which are likely to be fatiguing, may be associated
      with compromised safety for forest workers. IMPACT ON INDUSTRY: With an already
      slim margin of error present in forest operations, an impairment due to increased
      fatigue may constitute a significant risk factor for accidents and injuries in
      this workforce. The results indicate the need for further examination of shift
      and workload management among forestry workers, as well as a role for improving
      industry awareness about the causes and consequences of fatigue.

PMID- 11979638
TI  - The Illinois .08 law. An evaluation.
AB  - Lowering state blood alcohol concentration (BAC) limits to 0.08, though
      controversial, has been supported by most evaluation studies to date. The
      Illinois .08 BAC law implemented in 1997 provided a unique opportunity to
      evaluate the effect of the law without the simultaneous passage of an
      administrative license revocation (ALR) law, which has clouded some previous
      evaluations of the .08 laws. The proportion of all drinking drivers in fatal
      crashes was compared before versus after implementing the .08 law using time
      series analysis to evaluate 12 years of fatal crash data for Illinois and five
      bordering states. The results showed that the proportion of drinking drivers in
      fatal crashes decreased by 14% in Illinois and increased by 3% in bordering
      states. The proportion of drinking drivers in fatal crashes in Illinois, though
      increasing since 1995, was sharply reduced after passage of the .08 law in 1997,
      saving more than 100 lives in 1998 and 1999 than it would have without the .08
      law.

PMID- 11979639
TI  - Offshore safety case approach and formal safety assessment of ships.
AB  - PROBLEM: Tragic marine and offshore accidents have caused serious consequences
      including loss of lives, loss of property, and damage of the environment. METHOD:
      A proactive, risk-based "goal setting" regime is introduced to the marine and
      offshore industries to increase the level of safety. DISCUSSION: To maximize
      marine and offshore safety, risks need to be modeled and safety-based decisions
      need to be made in a logical and confident way. Risk modeling and decision-making
      tools need to be developed and applied in a practical environment. SUMMARY: This
      paper describes both the offshore safety case approach and formal safety
      assessment of ships in detail with particular reference to the design aspects.
      The current practices and the latest development in safety assessment in both the
      marine and offshore industries are described. The relationship between the
      offshore safety case approach and formal ship safety assessment is described and
      discussed. Three examples are used to demonstrate both the offshore safety case
      approach and formal ship safety assessment. The study of risk criteria in marine
      and offshore safety assessment is carried out. The recommendations on further
      work required are given. IMPACT ON INDUSTRY: This paper gives safety engineers in
      the marine and offshore industries an overview of the offshore safety case
      approach and formal ship safety assessment. The significance of moving toward a
      risk-based "goal setting" regime is given.

PMID- 11979640
TI  - What are the implications of the ADA in case management practice?

PMID- 11979641
TI  - Preparing for crisis--occupational health nurses respond.

PMID- 11979642
TI  - Terrorism--insights from the front line. Interview by Eileen Lukes.

PMID- 11979643
TI  - Managing during times of uncertainty. Part I--Short-term strategies.
AB  - During times of uncertainty, nurse managers must first and foremost act like
      leaders. They must be visible, stay focused on the situation at hand, demonstrate
      congruency, convey empathy to their employees, and communicate effectively. While
      this discussion has dealt with some "short term" approaches to handle uncertain
      situations, short term may be hours, days, or weeks depending on the type of
      crisis or situation. The strategies are critical to managing situations during
      the period immediately following an unexpected event. However, these strategies
      do not become obsolete as managers begin to address the long term ramifications
      of the event. Rather, they should serve as a foundation and guide for future
      management activity.

PMID- 11979644
TI  - Honesty and Ethics in the professions--Gallup poll results.

PMID- 11979645
TI  - Anthrax attack at the United States Capitol. Front line thoughts.
AB  - One great fear was realized on October 15, 2001 when United States citizens
      witnessed firsthand the unprecedented release of anthrax into a community.
      Although the office of the Attending Physician to Congress had been preparing for
      such an unthinkable act, lessons were learned as the events unfolded. The
      following is a summary of the findings: Preparation, planning, and frequent
      review of bioterrorism response procedures are essential. Effective communication
      remains the key to successful team performance. Briefings conducted daily and on
      an as needed basis shape the progress and performance of the team members.
      Electronic mail may not necessarily be the most effective way to disseminate
      critical information because not everyone can access the Internet outside of the
      work environment. Setting up a call center for answering client's questions is
      crucial. Clients potentially exposed to anthrax should be evacuated from the
      immediate area. Testing is not indicated for everyone, only those in the
      immediate areas. Allow health care personnel to decide whom should be tested.
      Such health care decisions must not be made based on anxiety or expediency. A
      data collection template should be set up in advance. This template should
      include, at least, the following: name, date of birth, social security number,
      the physical location of where the client might have been exposed, antibiotics
      administered and dosage, test results, and home and work phone number. This
      should be networked so a group can access and update data in real time. If the
      occupational health clinic has its own pharmacy, have a pill counter available to
      help with antibiotic distribution. The team should meet several times daily to
      ensure dissemination of a reliable and consistent message to the clients. Team
      members should be prepared to review the medical aspects of anthrax with clients
      on a frequent basis. A website with updated information might prove helpful for
      those with Internet access. This experience provided a unique opportunity for the
      Office of the Attending Physician to Congress to put its bioterrorism plan into
      action. Nothing substitutes for preparedness. Communication was the most
      important tool because it kept the team informed and focused on the mission at
      hand. It behooves all occupational health nurses to begin preparing for future
      acts as extraordinary as the anthrax attack that occurred on October 15, 2001.

PMID- 11979646
TI  - Planning for biological disasters. Occupational health nurses as "first
      responders".
AB  - 1. As a result of recent terrorist events, there is an immediate need for
      occupational nurses to review their disaster plans and to develop strategies to
      cope with bioterrorism in their workplaces. 2. The Centers for Disease Control
      and Prevention has identified three major categories of biological weapons.
      Category A, which is the highest priority category (and the focus of this
      article), includes smallpox, anthrax, botulism, plague, tularemia, filoviruses,
      and adenoviruses. Dealing with bioterrorism requires occupational health nurses
      to be familiar with these organisms, including their pathophysiology and methods
      of prevention, detection, and treatment. 3. Five principles can be used to guide
      responses to a biological attack. Incorporation of these principles into disaster
      planning will increase the effectiveness of responses to bioterrorism, if and
      when it occurs. Developing a plan of action before an event occurs will greatly
      enhance the likelihood that the repercussions of such an event are minimized.

PMID- 11979647
TI  - Psychosocial responses to biological and chemical terrorist threats and events.
      Implications for the workplace.
AB  - 1. Both biological and chemical weapons (BCW) could potentially be used in future
      terrorist attacks on U.S. workplaces and communities. 2. Threats of BCW terrorism
      may lead to anxiety, adverse health effects, and the exacerbation of psychiatric
      symptoms and syndromes in workers and managers. 3. Actual BCW attacks will likely
      cause both acute and chronic mental disorders in a significant number of
      surviving victims who may also be employees or employers. 4. Occupational health
      nurses can help prevent or remediate maladaptive psychological responses by
      educating themselves and their work forces, assisting in a risk assessment of the
      workplace, understanding disaster planning, and assisting management in policy
      formulation and psychosocial triage.

PMID- 11979648
TI  - Occupational response to terrorism.
AB  - Occupational health nurses are facing new challenges that seriously imperil
      health and safety in the workplace. The risks faced in the current world pose
      threats for which the occupational health nurse may not be prepared. These
      threats go beyond any unexpected workplace emergency. It is critical for all
      occupational health professionals to understand the implications of these modern
      threats and the proper response procedures, including the limits of a safe and
      prudent response. This knowledge will prevent further fatalities. Occupational
      health nurses need to translate this knowledge into corporate policies and
      procedures written so safety is the paramount consideration.

PMID- 11979649
TI  - Group wellness in the workplace.

PMID- 11979650
TI  - An integrated critique of the efficacy of topical mupirocin in preventing
      catheter-related Staphylococcus aureus infections in peritoneal dialysis clients.
AB  - Several epidemiological studies indicate that, for two reasons, Staphylococcus
      aureus (SA) nasal carriage is a risk factor for developing SA infections in
      peritoneal dialysis (PD) clients. First, nasal carriage is prevalent in these
      clients due to the nature of their disease. Second, there is a significant
      relationship between nasal and hand carriage of the SA organism. Because PD
      clients require frequent catheter handling to receive therapy, they are at risk
      for catheter contamination. Two prospective randomized control trials and two
      prospective cohort trials with historical controls were selected for review.
      Emphasis was placed on the design feature of a comparison or control group in
      order to find empirical support for the efficacy of topical mupirocin (Bactroban)
      as an infection control measure. The four studies selected also used two methods
      of application, the first application was to the nares and the second was to the
      catheter exit site. The result of the analysis revealed a weak support for the
      prophylactic role of topical mupirocin in preventing SA exit-site infections
      (ESI) in PD clients. Well-controlled prospective, randomized studies with
      sufficiently large sample sizes to produce statistically and clinically
      significant results for the prophylactic role of mupirocin are lacking. In light
      of the analysis, the advocacy of several practice implications involving client
      education and timely follow-up, staff training, and client comfort are warranted.

PMID- 11979651
TI  - Predicting methanol clearance during hemodialysis when direct measurement is not
      available.
AB  - The appropriate treatment of a patient with methanol intoxication includes the
      use of a competitive inhibitor of alcohol dehydrogenase (ethanol, p.o. or i.v.,
      or fomepizole) to prevent the metabolism of methanol to formaldehyde and formic
      acid. Where available, dialysis can be added to this therapy, since methanol is
      cleared well by hemodialysis. The ability to predict the time course of methanol
      elimination in any given patient is an essential factor in planning his or her
      care. Where the availability of ethanol, bicarbonate, nursing time, or dialysis
      machines is limited, such predictions can be used to allocate these resources
      quite accurately within a couple of hours of starting treatment. Even when direct
      measurement of methanol by gas chromatography is not readily available, its level
      can be estimated indirectly by a quick and easy method, using available
      laboratory values. The length of time necessary to clear the methanol below a
      toxic level can be predicted accurately. Careful interpretation of laboratory
      values can result in early treatment, correct treatment time, and a positive
      patient outcome.

PMID- 11979652
TI  - Upadate on oral treatments for type II diabetes.

PMID- 11979653
TI  - Spring screening for asthma; staying alert to allergic reactions.

PMID- 11979654
TI  - When two heads are better than one: school-based health center staff joining
      school nursing services to meet the health care needs of children.

PMID- 11979655
TI  - Development of a school crisis team.

PMID- 11979656
TI  - Fabry disease: a unique challenge for nurses.

PMID- 11979657
TI  - Treating ADHD in school settings.

PMID- 11979658
TI  - Ocular emergencies: a quick reference.
AB  - Sight is precious, considered by many to be the most essential of the five
      senses. Children's eyesight is especially important, because good vision is
      related to learning. Regular eye examinations are needed to maintain proper eye
      health, since some serious eye disorders produce no early warning symptoms.
      Although prevention is the best defense, eye problems or injuries still occur
      suddenly and unexpectedly. When they do, recognizing their signs and symptoms and
      knowing what to do is vital to preserving sight.

PMID- 11979659
TI  - Hungry youngsters = insufficient learning.

PMID- 11979660
TI  - Student health: a balancing act for school nurses. The more or less of it.

PMID- 11979661
TI  - Maintaining a healthy balance meal planning for the diabetic.

PMID- 11979662
TI  - Diabetes: a struggle for sugar control.

PMID- 11979663
TI  - Preventing teen pregnancy--a report on what works.

PMID- 11979664
TI  - Strategies announced promoting responsible sexual behavior and health.

PMID- 11979665
TI  - [The French and pain: a paradoxical fear].

PMID- 11979666
TI  - [The psychology of care].

PMID- 11979667
TI  - [A nurse in hemodialysis].

PMID- 11979668
TI  - [HIV/AIDS: in France, too, people still die of it].

PMID- 11979669
TI  - [Vaccination; not for tomorrow, but...].

PMID- 11979670
TI  - [What should one do in an accident involving bleeding?].

PMID- 11979671
TI  - [February 1993-February 2002: 9 years for realizing the decree of professional
      practice].

PMID- 11979673
TI  - [Placement in professional situations in emergency services; is it feasible?].

PMID- 11979672
TI  - [Organization and hygiene: the role of the nurse].

PMID- 11979674
TI  - [Discharge of hospitalized patients: an act of care].

PMID- 11979675
TI  - [Resocialization outside of institutions].

PMID- 11979676
TI  - [Antivitamins K, one must return to their good usage].

PMID- 11979677
TI  - [Professional action and responsibility of nurses (Decree number 2002-194 of
      February 11 2002 relating to professional actions and the exercise of the nursing
      profession)].

PMID- 11979678
TI  - [17 beta-estradiol. as a patch. An elixir of youth as a prescription for the
      menopausal woman].

PMID- 11979679
TI  - [Agreement: advanced directives].

PMID- 11979680
TI  - [Seropositive women and medical help in pregnancy].

PMID- 11979681
TI  - [Operation "Return to work"; a limited success].

PMID- 11979682
TI  - [Increasing the availability of organs].

PMID- 11979684
TI  - Seeking collaboration within primary health care.

PMID- 11979683
TI  - [Risks in the health professions].

PMID- 11979685
TI  - Submissions on Health and Safety bill called for.

PMID- 11979686
TI  - Changes to national immunisation schedule.

PMID- 11979687
TI  - Caring for the frail and vulnerable.

PMID- 11979688
TI  - Gaining insight into the experience of diabetes.

PMID- 11979689
TI  - Learning to become a patient.

PMID- 11979690
TI  - The role of health care assistants in hospitals.

PMID- 11979691
TI  - Giving care in 2002.

PMID- 11979692
TI  - Challenging and changing the culture of nursing.

PMID- 11979693
TI  - Valuing caregivers' contribution.

PMID- 11979694
TI  - Restoring caregivers' pay and conditions.

PMID- 11979695
TI  - Canterbury nurses' strike of national significance.

PMID- 11979696
TI  - Chiropractors support Canterbury nurses.

PMID- 11979697
TI  - Article on religious needs comes under fire.

PMID- 11979698
TI  - New graduate nurse suggests solution to staffing shortages.

PMID- 11979699
TI  - NZNO dedicates week to caregivers.

PMID- 11979700
TI  - Canterbury nurses vote for settlement.

PMID- 11979701
TI  - Stats & facts. More consumer cost sharing in pharmacy benefit.

PMID- 11979702
TI  - Lessons learned: bricks, clicks, and E-care.

PMID- 11979703
TI  - Disenrollment carries a cost that MCOs cannot ignore.

PMID- 11979704
TI  - An opportunity for increased efficiency.

PMID- 11979705
TI  - The cost of diabetes in the presence of comorbid conditions.
AB  - Disease management programs usually focus on the target disease, with little
      emphasis on clinical comorbidity. The research presented here used retrospective
      analysis to determine the incremental costs of diabetes to a state Medicaid
      program when diabetes occurred with other common chronic illnesses. The study
      revealed that the incremental costs of diabetes were influenced by the costs of
      the chronic illnesses associated with diabetes. The following methodology is
      intended to improve the benchmarking and evaluation of diabetes disease
      management programs.

PMID- 11979706
TI  - Patients will continue to gather health care information from the Web.

PMID- 11979707
TI  - Countdown to HIPAA compliance.
AB  - As compliance deadlines for the Health Insurance Portability and Accountability
      Act close in, the author details specific actions that must be taken to ensure
      that covered entities are indeed compliant with all of the Act's provisions.

PMID- 11979708
TI  - Combining mandatory health insurance and medical savings accounts.
AB  - The American tradition of freedom of choice is mirrored exceptionally well in the
      health care industry. The consequences of this system are the highest health care
      costs in the world and 38.7 million uninsured. Implementation of mandatory, high
      deductible health insurance in conjunction with a medical savings account for
      every resident could have several benefits, and it may engender bipartisan
      support.

PMID- 11979709
TI  - MA hospitals go online to improve guideline compliance.

PMID- 11979710
TI  - Health plan hopes sharing data will boost cholesterol treatment.

PMID- 11979711
TI  - New tool allows cardiologists to refine estimates of surgery risk.

PMID- 11979712
TI  - Automating procedure information eliminates gap in hospital systems.

PMID- 11979713
TI  - Endocrinologists use handhelds to target correct insulin dose.

PMID- 11979715
TI  - Anesthesia benchmarks available for clinical, financial operations.

PMID- 11979714
TI  - Consumer data help Humana create, market new products.

PMID- 11979716
TI  - Texas hospital calculates savings from Web-based credentialing.

PMID- 11979717
TI  - Streptococcus mutans levels and caries prevalence in low-income schoolchildren.
AB  - Previous studies have shown that persons having high Streptococcus mutans levels
      in the saliva are "at risk" for dental caries. Most investigators agree, that if
      high levels of S. mutans were identified early in the life of at-risk children,
      dental decay could be reduced or eliminated through intervention. The purpose of
      this study is to show an association between S. mutans levels and caries
      prevalence in a sample of elementary school children. The study group consisted
      of 242 school children, ages 5-13 years. The subjects were divided into two age
      groups, 5-8 years and 9-13 years. Approximately 59 percent were African
      Americans. The sample of 242 children were equally females and males, 50 percent
      in each group. The Dentocult SM Test was used to make S. mutans determinations.
      The df-t index was used to determine the number of decayed and filled teeth of
      children ages 5-8 years; the DMF-T Index estimated the number of decayed, missing
      or filled teeth of children ages 9-13 years. Dental caries were found in 58
      percent of the children (mean = 2.67, and range of 1-11). Approximately 47
      percent of the children with caries had high S. mutans levels (100K-1M). Females
      had higher S. mutans levels than males in the 9-13 age group, p < .05. Analysis
      of Variance Test indicated that S. mutans levels for older females (ages 9-13)
      were significantly higher than those observed in males the same age (p < .01).
      This trend was not observed in younger children, ages 5-8 years. In addition, no
      significant difference or interaction was noted by sex for S. mutans levels and
      decayed or filled teeth (df-t) for younger children. We conclude that high levels
      of Streptococcus mutans are related to increased number of decayed teeth and
      conversely, low Streptococcus mutans levels are related to fewer dental caries.
      This study was supported in part by Colgate-Palmolive Company and the National
      Dental Association Foundation, Inc.

PMID- 11979718
TI  - Microleakage of flowable composite resins when utilized as liners in Class II
      posterior composite resin restorations.

PMID- 11979719
TI  - Security in dental office computing.
AB  - Dental office computers are increasingly used to store critical financial and
      clinical data. That data is subject to loss or alteration from a number of
      possible sources. Secure communications, security of the computer system from
      outside attacks, and data backup are discussed.

PMID- 11979720
TI  - Dentists in Tennessee evaluate safer needle devices.

PMID- 11979721
TI  - Nursing heroes of 9-11-01.

PMID- 11979722
TI  - Non-members have a way of contributing to their professional association.

PMID- 11979723
TI  - Assembly Health & Human Services Committee to hold hearing on nursing shortage
      and staffing.

PMID- 11979724
TI  - [The roles of the prostanoids played in the body].
AB  - The actions of prostanoids in various physiological and pathophysiological
      conditions have been examined using mice lacking the prostanoid receptors. PGD2
      was found to be a mediator of allergic asthma. Prostaglandin (PG) I2 worked not
      only as a mediator of inflammation but also as an antithrombotic and cardio
      protective agent. Several important actions of PGE2 are brought out via the PGE2
      receptor subtype EP3; PGE2 participated in the regulation of platelet function,
      and it worked as a mediator of febrile responses to both endogenous and exogenous
      pyrogens. These novel findings on the roles of the prostanoids would contribute
      to the development of drugs targeting the prostanoid receptors.

PMID- 11979725
TI  - [P450 and carcinogenesis].
AB  - Multiple forms of cytochrome P450 play important roles in metabolic activation of
      a variety of environmental procarcinogens. Large species differences in substrate
      specificities between experimental animals and humans are critical factors in
      evaluation of chemical safety. To study the role of human P450s in genotoxic
      activation of environmental chemicals, transgenic bacteria expressing both human
      P450s and P450 reductase have been developed for the mutagenicity test. Mice
      lacking CYP1A2, and CYP1B1, and CYP2E1 were prepared to investigate the mechanism
      of procarcinogen activation in vivo. The first human transgenic animals were mice
      carrying human fetus-specific CYP3A7. Using these transgenic mice, mutagenic
      activation of a natural mycotoxin, aflatoxin B1, catalyzed by CYP3A7 in vivo was
      demonstrated. This observation was clear in extrahepatic tissues that did not
      express mouse CYP3A enzymes. In conclusion, P450s are key factors involved in
      metabolic activation of environmental procarcinogens for their biological
      actions.

PMID- 11979726
TI  - [Learning/memory and drug dependence].
AB  - We investigated the possible mechanisms of development of latent learning and
      morphine dependence by the methods of behavioral pharmacology and confirmed them
      by using mutant mice. The heterozygous mice for the tyrosine hydroxylase (TH)
      gene and for the cyclic AMP (cAMP) response element binding protein (CREB)
      binding protein (CBP) gene showed the impairment of latent learning in the water
      finding task, and these mice did not develop morphine dependence. The spatial
      learning and hippocampal long-term potentiation (LTP) were normal in the both
      mutants. TH heterozygous mice showed a reduction of high K(+)-evoked
      noradrenaline release in the frontal cortex measured by the microdialysis
      technique and of cAMP content in the brain. In conclusion, the results of mutant
      mice suggest that the alternation of catecholamine biosynthesis and cAMP signal
      pathways may play a key role in development of latent learning and morphine
      dependence, and they furthermore show that the expression of genes mediated by
      phosphorylated CREB may be involved in the development of latent learning and
      morphine dependence.

PMID- 11979727
TI  - [Preparation of the gene targeted knockout mice for human premature aging
      diseases, Werner syndrome, and Rothmund-Thomson syndrome caused by the mutation
      of DNA helicases].
AB  - The list of human RecQ helicase comprises RecQ1, BLM (Bloom syndrome), WRN
      (Werner syndrome), RTS (Rothmund-Thomson syndrome), and RecQ5. Of these, the
      defective BLM, WRN, and RTS helicases are responsible for distinct but
      overlapping clinical features suggesting premature aging and an enhanced risk of
      cancer, which apparently stems from chromosomal instability in the cells of
      tissues and organs where expression of the helicase genes are specified. In an
      effort to obtain an animal model for these diseases, we performed gene target
      experiments to generate the WRN and RTS knockout mice.

PMID- 11979728
TI  - [Genetic basis of autonomic gastrointestinal motility and pathophysiological
      models].
AB  - The origin of rhythmicity in gastrointestinal motility was long thought to
      involve the activity of interstitial cells of Cajal (ICC) that locate in close
      association with enteric neurons and smooth muscle cells. We have demonstrated
      that significant decrease in the number of cells immunopositive to c-Kit, a type
      of tyrosine kinase receptor, in the gastrointestinal tract of mice mutated at the
      W/c-kit locus and BALB/c mice administered with neutralizing c-Kit antibody leads
      to the impaired autonomic motility of the gastrointestinal tract. It is also
      demonstrated that ICC express c-kit which plays important roles in development
      and maintenance of the ICC network in the gastrointestinal tract. ICC, derived
      from mesenchymal cells, are classified into smooth muscle type and fibroblast
      type by their morphology and tissue location. The ligand for c-Kit, Sl factor
      (SLF), has shown to be expressed in enteric neurons and gastrointestinal smooth
      muscle cells. Studies with mutant mice and transgenic mice have suggested that
      functional c-Kit/SLF is required for the differentiation and proliferation of ICC
      as pacemakers and mediators of neural regulation in gastrointestinal motility.
      Here we review the genetic basis of autonomic gastrointestinal motility and the
      pathophysiological models.

PMID- 11979729
TI  - [Calcium channel subtypes mediating central synaptic transmission].
AB  - It is well established that neurotransmitter release is triggered by Ca2+ entry
      into the presynaptic terminals through voltage-dependent Ca2+ channels. In the
      mammalian central nervous system, multiple types of Ca2+ channels including N
      type, P/Q-type and other types mediate fast synaptic transmission.
      Electrophysiological studies using type-specific antagonists for Ca2+ channels
      have estimated the relative contribution of N-, P/Q- and other types of Ca2+
      channels in excitatory and inhibitory synaptic transmission in the hippocampus,
      cerebellum, spinal cord, brain stem, and striatum. A recent study has
      demonstrated that activation of presynaptic dopamine D2-like receptors
      selectively block N-type Ca2+ channels to reduce GABA release onto cholinergic
      interneurons in the rat striatum. In addition, it has been recently clarified
      that the contribution of N-type Ca2+ channels to synaptic transmission is
      restricted to the early postnatal period at synapses in auditory brain stem,
      cerebellum, or thalamus. Advanced morphological studies are necessary for the
      further understanding of the subcellular localization of each subtype of Ca2+
      channels and receptors modulating the transmitter release through Ca2+ channel
      activity in relation to the release sites in the presynaptic terminals.

PMID- 11979730
TI  - [The analysis of protein-protein interaction with special reference to PRIP-1].
AB  - Analysis of protein-protein interaction is one of the powerful methods for
      elucidating the new functions of functionally unknown proteins. Using this
      approach, we isolated two proteins interacting with PRIP-1, which was isolated as
      a new Ins(1,4,5) P3 binding protein from brain. One was protein phosphatase 1
      catalytic subunit (PP1c) and the other was GABARAP (GABAA-receptor-associated
      protein). The region of PRIP-1 responsible for their interaction was the site
      preceding to the pleckstrin homology domain of PRIP-1 for PP1c and the EF-hand
      motifs of PRIP-1 for GABARAP, which were determined by beta-galactosidase assay
      of yeast two-hybrid system. The association between PRIP-1 and PP1c was confirmed
      in vitro by a pull-down assay, a far-western assay, an immunoprecipitation
      analysis and a surface plasmon resonance analysis. The interaction of PRIP-1 with
      PP1c resulted in inhibition of the catalytic activity of PP1c in a PRIP-1
      concentration-dependent manner. The association between PRIP-1 and GABARAP was
      also confirmed by a pull-down assay, and we found that PRIP-1 competitively
      inhibited the binding of the gamma 2 subunit of the GABAA receptor to GABARAP in
      vitro. Our electrophysiological and behavioral analysis of PRIP-1 knockout mice
      revealed that PRIP-1 is essential for the function of GABAA receptors, especially
      in response to the agents acting on the gamma 2 subunit.

PMID- 11979731
TI  - [Zafirlukast (Accolate): a review of its pharmacological and clinical profile].
AB  - Today, bronchial asthma is considered as a chronic inflammatory disease of the
      airway. It has been revealed that various chemical mediators are involved in the
      onset of bronchial asthma. Among them, particularly, the peptide leukotrienes,
      LTC4, LTD4 and LTE4, have been known to play a pathophysiological important role
      in asthma. Zafirlukast binds to the CysLT1 receptors competitively with these
      peptide leukotrienes and inhibited peptide leukotriene-induced constriction of
      isolated guinea pig trachea and lung parenchyma and isolated human bronchi.
      Zafirlukast also demonstrated dose-dependent inhibition of LTD4-induced dyspnea
      in guinea pigs in vivo. Zafirlukast demonstrated preventive and alleviating
      effects on LTD4- and ovalbumin-induced decrease in the lung function. Zafirlukast
      also displayed inhibitory effects on LTD4-induced eosinophil infiltration into
      airway tissues and bronchial edema. In sheep naturally allergic to Ascaris suum
      antigen, zafirlukast exhibited inhibitory effects on Ascaris suum antigen-induced
      immediate and late type airway constriction and increase in airway
      hypersensitivity. In clinical pharmacology studies, zafirlukast inhibited LTD4-
      or allergen-induced airway constriction and exercise-induced reduction of the
      pulmonary function. It also prevented onset of methacholine-induced airway
      hyperresponsiveness. Furthermore, good efficacy of zafirlukast was confirmed in
      clinical trials in adult bronchial asthma patients. As above, zafirlukast is
      effective for treatment of bronchial asthma, which is attributed to its peptide
      leukotriene antagonistic action.

PMID- 11979732
TI  - Systems to rate the strength of scientific evidence.

PMID- 11979733
TI  - [Recent advance in understanding mechanisms of fibrogenesis and fibrolysis in
      hepatic fibrosis].

PMID- 11979734
TI  - [Forefront of therapy for hepatic fibrosis].

PMID- 11979735
TI  - [Anti-Helicobacter pylori effects of Bainiku-ekisu (concentrate of Japanese
      apricot juice)].
AB  - Helicobacter pylori (H.p.) bacteria are the major causes of gastro-duodenal
      disease, and some association with stomach cancer has been suggested. Recently,
      H.p. eradicating treatment has been practiced using antibiotics and proton-pump
      inhibitors. However, at the same time, some reports have been made on the side
      effects of this treatment; allergic reactions and uneffective resistant bacteria.
      Under these circumstances, there is a strong need for medicines, which are less
      harmful to the body, can be administered repeatedly, are less expensive, and yet
      as effective as antibiotics in inhibiting the bacteria, and in fact, some studies
      have been undertaken in this regard. We placed our focus on Bainiku-ekisu
      (Concentrate of Japanese apricot juice) which, as a Japanese folk remedy, has
      been used for the treatment of gastritis and enteritis since ancient times, and
      studied its bacteriosterile affects. The major ingredients of Bainiku-ekisu are
      citric acid (32%) and malic acid (11%), while its pH represents strong acid. We
      measured the bacteriosterile effects of Bainiku-ekisu by culturing ten H.p.
      strains originating from gastro mucous membrane respectively in a Bainiku-ekisu
      concentration of 0.156%, 0.313%, 0.625% and 0.9%, and measured the level of MIC
      (minimum inhibiting concentration of development). As a result, out of ten H.p.
      strains four of them presented strong bacteriosterile effects in a concentration
      of less than 0.156%, and six of them, in a concentration of less than 0.313%.
      Furthermore, in order to measure the bacteriosterile effects against H.p. in the
      stomach we measured the quantity of bacteria in 0 minutes, five minutes, and ten
      minutes after mixing ten H.p. strains suspended in physiological salt solution
      with a Bainiku-ekisu solution of 0.3% and 0.9% dissolved in aseptic physiological
      salt solution. As a result, within five minutes after mixing, every one of the
      ten H.p. strains was observed to present strong bacteriosterile effects. These
      results suggest that Bainiku-ekisu can be considered as a fool likely to prevent
      the development of H.p. as well as the future possibility of making clinical
      applications to H.p. infection.

PMID- 11979736
TI  - [A case of multiple gastric carcinoid tumor with type A gastritis treated by
      distal gastrectomy].

PMID- 11979737
TI  - [A case of Hodgkin's disease of mesenteric origin].

PMID- 11979738
TI  - [A case of mesenteric panniculitis of small intestine diagnosed by abdominal CT
      scan, and improved with conservative therapy].

PMID- 11979739
TI  - [A case of severe alcoholic hepatitis with successfully treated by the therapy
      for hypercytokinemia and granulocytic hyperelastasemia].

PMID- 11979740
TI  - [A case of Cowden's disease accompanied by fibrous polyp of the gallbladder].

PMID- 11979741
TI  - [A case report of hemorrhagic pancreatic pseudoaneurysm fenestrated into the
      flexura duodeni jejunalis].

PMID- 11979742
TI  - [Analyses of the mutations of AML 1 gene in myelodysplastic syndromes].

PMID- 11979743
TI  - [Clinical integration and grouping of malignant lymphoma].

PMID- 11979744
TI  - [Wilms tumor gene (WT1) as a marker for minimal residual disease in leukemia].

PMID- 11979745
TI  - [The strategy for the treatment of myelodysplastic syndromes].

PMID- 11979746
TI  - [Current problems of hemophilia treatment].

PMID- 11979747
TI  - [Effectiveness of oral vitamin B12 therapy for pernicious anemia and vitamin B12
      deficiency anemia].
AB  - We investigated the efficacy of oral vitamin B12 (B12) therapy in patients with
      B12-deficiency anemia. Between June 1994 and June 2000, 17 patients, who were
      diagnosed as having B12-deficiency anemia and gave their informed consent, were
      enrolled in this study. Of these patients, 7 were further treated with a
      maintenance dose of methylcobalamin (1,500 micrograms daily for 7 days every 1-3
      months). Correction of hematological and neurological abnormalities was prompt.
      The hemoglobin level and serum concentration of B12 were normalized within two
      months after starting the treatment. Recovery from neurological disturbance was
      observed within one month. To maintain a normal serum concentration of B12, a 7
      day regime of administration was needed every month in 3 patients, every 2 months
      in 3 patients, and every 3 months in 1 patient. These results demonstrate the
      effectiveness of oral cobalamin therapy, and also that oral intermittent therapy
      is useful for maintaining a normal serum B12 concentration. Oral cobalamin
      therapy might be as effective as conventional injection therapy, and useful for
      long-term treatment.

PMID- 11979748
TI  - [Significance of soluble interleukin-2 receptor alpha chain in the management of
      patients with malignant lymphoma: a multi-center study].
AB  - A multi-center series of 117 patients with malignant lymphoma were analyzed to
      evaluate the clinical significance of soluble interleukin-2 receptor alpha chain
      (sIL-2R alpha). The initial levels of sIL-2R alpha ranged from 277 U/ml to 22,800
      U/ml with a mean level of 3,451 +/- 4,268 U/ml and a median level of 1,600 U/ml.
      The sIL-2R alpha levels of the diffuse lymphoma/intermediate-grade subtypes
      defined by the LSG classification/Working Formulation were higher than those of
      the follicular lymphoma/low-grade subtypes. There was a tendency for B-cell
      lymphomas to show higher sIL-2R alpha levels than T-cell lymphomas. The sIL-2R
      alpha level was correlated with the Ann Arbor clinical stage (I, II versus III,
      IV), presence or absence of B symptoms, and performance status (0, 1 versus 2, 3,
      4) of the patients. The sIL-2R alpha levels were in good accordance with the four
      risk groups defined by the International Prognostic Indices. Of 21 patients whose
      tumor burden was serially measured, the coefficients of correlation between sIL
      2R alpha and tumor mass were > 0.6 in 18 cases. Sixty-two patients achieved
      complete remission (CR) during the study; the initial and minimum sIL-2R alpha
      levels were lower than those of the non-CR patients. This study confirmed that
      sIL-2R alpha is a convenient and useful marker in the management of malignant
      lymphoma.

PMID- 11979749
TI  - [Acute pancreatitis following hematopoietic stem cell transplantation: prevalence
      and cause of pancreatic amylasemia].
AB  - To clarify the frequency and cause of acute pancreatitis following hematopoietic
      stem cell transplantation (SCT), we examined retrospectively 57 patients who
      underwent hematopoietic SCT in our institute from 1984 to 2000. Twelve (21%) of
      the patients showed an elevated level of serum pancreatic amylase following SCT.
      However, only 3 patients were clinically diagnosed as having acute pancreatitis.
      Among these 12 patients, 11 had undergone allogeneic transplantation.
      Furthermore, patients who had undergone unrelated transplantation (7/16; 44%)
      tended to show a higher incidence of increased amylase than those who had
      undergone related transplantation (4/24; 17%). Six patients were at an advanced
      stage of acute GVHD (grade III or IV) and all showed an elevated level of serum
      amylase, whereas only four patients showed an elevated serum amylase level among
      34 with mild acute GVHD (grade I or II) or without GVHD. Furthermore, five out of
      12 patients who showed an increased amylase level were concurrently diagnosed as
      having viral infection such as cytomegalovirus, adenovirus, or varicella zoster
      virus. We conclude that pancreatitis following SCT occurs more often than
      realized, and is mostly subclinical. This is closely associated with severe acute
      GVHD, and possibly viral infection.

PMID- 11979750
TI  - [Continuous infusion of recombinant activated factor VII during and after elbow
      arthroplasty in a hemophilia A patient with inhibitors].
AB  - Recombinant activated factor VII (rFVIIa) is a recently added new agent for the
      treatment of hemophiliacs with inhibitors. A major drawback to the use of rFVIIa
      is its short half-life, necessitating frequent and intermittent bolus injections.
      Continuous infusion of rFVIIa has been reported as a feasible, convenient, safe
      and cost-effective alternative to intermittent bolus injections. We report the
      use of continuous rFVIIa infusion during and after left elbow arthroplasty in a
      hemophiliac with a high titer of inhibitor to factor VIII. rFVIIa was
      administered as a bolus injection (100 micrograms/kg) at the start of the
      operation, after which continuous infusion (10-30 micrograms/kg/h) was
      immediately started and continued for 6 days. Tranexamic acid (50 mg/kg/day,
      p.o.) was also administered as an antifibrinolytic treatment. Laboratory
      monitoring of hemostatic efficacy was performed in this case using prothrombin
      time and the thrombelastogram. Finally, effective intra- and postoperative
      hemostasis and normal healing of the surgical incisions were achieved, except for
      local thrombophlebitis. Although the optimal maintenance or target level of
      rFVIIa has been a matter of debate, we consider continuous infusion of rFVIIa to
      be a feasible, convenient, safe and cost-effective alternative to intermittent
      bolus injections.

PMID- 11979751
TI  - [Successful treatment of invasive pulmonary aspergillosis with G-CSF and M-CSF
      during long-term bone marrow suppression in hypoplastic leukemia].
AB  - A 52-year-old man was admitted for treatment of hypoplastic leukemia (M 1). After
      induction chemotherapy with IDR and AraC, the patient developed prolonged febrile
      neutropenia, and a diagnosis of invasive pulmonary aspergillosis was made. We
      started administration of AMPH-B and G-CSF, but the patient showed no clinical
      improvement. M-CSF was added to the regimen, and this led to an increase in the
      white blood cell count with resolution of pneumonia. It is suggested that
      administration of M-CSF with antibiotics and G-CSF may be beneficial for treating
      acute leukemia patients with prolonged febrile neutropenia after intensive
      chemotherapy.

PMID- 11979752
TI  - [A family with dominant-phenotype Beta-thalassemia].
AB  - We report a 43-year-old Japanese woman with microcytic and hypochromic anemia,
      who had been erroneously diagnosed as having iron deficiency anemia 20 years
      previously at the time of her first labor, and treated with iron and blood
      transfusion. At the present visit to our clinic, she was found to have an
      increased HbA2 level and prolonged glycerol lysis time. Genetic analysis of the
      beta-globin gene revealed deletion of 3 bases at codons 127/128 (CAG/GCT-->CCT).
      A genetic study of the patient's family showed that two of her four children
      possessed the same mutation. The patient had mild anemia, her first son had very
      mild anemia, and her second daughter had moderate anemia with hemolysis. These
      affected family members were diagnosed as having dominant-phenotype beta
      thalassemia.

PMID- 11979753
TI  - [Thoracic aortic aneurysm with chronic disseminated intravascular coagulation
      treated successfully with orally administered camostat mesilate, warfarin and
      aspirin].
AB  - We describe a case of thoracic aortic aneurysm complicated by chronic
      disseminated intravascular coagulation (DIC). Initially the DIC was controlled
      successfully by administration of gabexate mesilate and dalteparin. However,
      because these drugs were given intravenously, the patient could not be
      discharged. Subsequently, the DIC was treated successfully by changing to orally
      administered camostat mesilate, warfarin and aspirin, which allowed the patient
      to leave hospital.

PMID- 11979754
TI  - [Development of overt hemolytic anemia after splenectomy for thrombocytopenia in
      Evans syndrome with negative Coombs test].
AB  - A 69-year-old man was diagnosed as having idiopathic thrombocytopenic purpura
      (ITP) in April 2000, and treated with prednisolone (PSL) without effect.
      Splenectomy performed in June 2000 had only a transient and marginal influence on
      his platelet count. Two months later, he developed autoimmune hemolytic anemia
      (AIHA) without Coombs test positivity, and his diagnosis was changed to Coombs
      negative Evans syndrome. Treatment with PSL led to recovery of his hemoglobin
      level, but not his platelet count. Although the mechanism responsible for
      development of AIHA after splenectomy in this patient with ITP remains unknown,
      close observation is required for any association with other autoimmune diseases
      such as SLE.

PMID- 11979755
TI  - [Leprosy reactions].
AB  - In leprosy, the causative bacteria, Mycobacterium leprae, will not threaten the
      lives of the hosts directly because they proliferate only slowly in the Schwann
      cells of the peripheral nerves. It is the "reactions" which give the patients
      irreversible morbidity through the inflammatory damages to the peripheral nerves.
      Physicians should be aware of the possibility of the state of the "reaction" when
      they examine leprosy patients. They also should be aware of the possibility of
      leprosy and the state of the "reaction" when they examine patients with cutaneous
      lesions and/or peripheral nerve disturbances, because it may be the first
      presenting symptom of the disease. In this review, recent advances on the issue
      about the reactions are discussed including pathogenesis, immunology, clinical
      features, pathology, treatment and prevention.

PMID- 11979756
TI  - Prevention of diabetes in non-obese diabetic mice by a single immunization with
      Mycobacterium leprae.
AB  - The incidence of overt diabetes was completely prevented by a single intradermal
      inoculation of Mycobacterium leprae (M. leprae) into Non-obese diabetic (NOD)
      mice as young as 6-7 weeks. Partial prevention was also observed in cases when 65
      kD heat-shock protein (hsp65) with Freund's incomplete adjuvant (FIA) was
      injected, and no prevention was observed by 38 kD with FIA immunization.
      Histological examination of pancreata demonstrated that control and M. leprae
      immunized mice at 24 weeks of age developed the insulitis even though the number
      of lymphocytes infiltrated in the treated ones were less than the controls.
      However, later, at 47 weeks of age, even the immunized mice become to develop
      very severe insulitis. Thus, M. leprae-immunization did not prevent the
      incidences of insulitis. The spontaneous development of serum antibody against
      hsp65 and 38 kD protein preceded the onset of diabetes in NOD mice. Lymphocytes
      response, IFN-gamma and IL-10 production of splenocytes cultures stimulated with
      hsp65 were examined to clue the reasons for the prevention of IDDM incidence by
      M. leprae immunization. The spontaneous development of anti-hsp65 T lymphocytes
      preceded the outbreak of overt IDDM in control NOD mice, but also appeared in M.
      leprae immunized cases in which the IDDM incidence was prevented, and both
      control and M. leprae immunized groups produced IFN-gamma and IL-10 by
      stimulation with hsp65.

PMID- 11979757
TI  - [Susceptibility to Mycobacterium leprae of congenic hypertensive nude rat
      (SHR/NCrj-rnu) and production of cytokine from the resident peritoneal
      macrophages].
AB  - We have established a congenic hypertensive nude rat strain, SHR/NCrj-rnu,
      carrying nude (rnu) and hypertension genes which was produced using females of
      the SHR/NCrj rat and males of the F344/NJcl nude rat by cross-intercross system
      for 12 generations. We demonstrated the susceptibility to M. leprae infection of
      SHR/NCrj-rnu rats as compared with F344/NJcl-rnu rats. SHR/NCrj-rnu rats were
      highly susceptible to M. leprae, and the SHR/NCrj-rnu rats of both sexes showed
      massive swelling of legs due to multiplication of M. leprae. However, F344/NJcl
      rnu rats of both sexes revealed very poor susceptibility to M. leprae. There was
      a wide difference in the susceptibility to M. leprae between the SHR/NCrj-rnu and
      the F344/NJcl-rnu rats. We also examined the cytokine production. The resident
      peritoneal macrophages of SHR/NCrj-rnu rats produced IL-1 alpha, IL-6, IL-10 and
      TNF alpha, whereas those of F344/NJcl-rnu rats produced only TNF alpha.

PMID- 11979758
TI  - The experience of a short-term specialist in Myanmar from February 5th to March
      4th, 2001.

PMID- 11979759
TI  - [CagA of H. pylori and gastric mucosal damage].

PMID- 11979760
TI  - [CagA antibody and pathophysiology of H. pylori infection].

PMID- 11979761
TI  - [Endotoxin (lipopolysaccharide) of Helicobacter pylori and gastric mucosal
      injury].

PMID- 11979762
TI  - [Ammonia and monochloramine generated by urease in Helicobacter pylori cause
      gastric mucosal injury].

PMID- 11979763
TI  - [Role of neutrophil-activating factor and IL-8 in the development of H. pylori
      induced gastric mucosal damage].

PMID- 11979764
TI  - [Helicobacter pylori infection in peptic ulcer disease].

PMID- 11979765
TI  - [Mechanism of gastric mucosal cell injury induced by reactive oxygen species and
      nitric oxide].

PMID- 11979766
TI  - [Effect of H. pylori infection on brain-gut peptide and acid secretion].

PMID- 11979767
TI  - [Heat shock protein--HSP 60 and gastric mucosal injury].

PMID- 11979768
TI  - [The gastric mucosal injury induced by the immune responses against Helicobacter
      pylori].

PMID- 11979769
TI  - [Gastric epithelial cell apoptosis and IL-18].

PMID- 11979770
TI  - [Helicobacter pylori impairs gastric mucosal microcirculation through inhibition
      of cell proliferation and induction of apoptosis on endothelial cells].

PMID- 11979771
TI  - [Pathogenesis of gastric mucosal microcirculatory damage].

PMID- 11979772
TI  - [Gastric mucosal hydrophobicity].

PMID- 11979773
TI  - [Peptic ulcer and environmental factor: with special focus on Helicobacter pylori
      infection].

PMID- 11979774
TI  - [H. pylori infection and host's genetic analysis using HLA polymorphisms].

PMID- 11979775
TI  - [Development of Helicobacter pylori eradication therapy].

PMID- 11979776
TI  - [Effects of NSAIDs on prostaglandin synthesis].

PMID- 11979777
TI  - [The mechanism of gastric mucin synthesis and secretion].

PMID- 11979778
TI  - [Neutrophil-endothelium interaction].

PMID- 11979779
TI  - [Significance of COX-2].

PMID- 11979780
TI  - [Reactive oxygen species and free radical reactions are involved in the
      pathogenesis of non-steroidal anti-inflammatory drugs-induced gastric mucosal
      injury].

PMID- 11979781
TI  - [Induction of syndecan-1 expression in parietal cells during gastric mucosal
      injury by NSAIDs].

PMID- 11979782
TI  - [Effect of NSAIDs on gastric mucosal damage induced by H. pylori infection].

PMID- 11979783
TI  - [Physiopathology of Helicobacter pyroli infection: Gastric acid secretion].

PMID- 11979784
TI  - [Physiopathology of Helicobacter pylori infection: Pepsinogen secretion].

PMID- 11979785
TI  - [Physiopathology of Helicobacter pylori infection: Gastric mucus secretion].

PMID- 11979786
TI  - [Physiopathology of Helicobacter pylori infection: Gastric mucosal protection].

PMID- 11979787
TI  - [H. pylori and para-neuron secretion (gastrin, somatostatin, histamine)].

PMID- 11979788
TI  - [H. pylori and gastric motility (including gastric emptying)].

PMID- 11979789
TI  - [Histopathology of peptic ulcers].

PMID- 11979790
TI  - [Histological and endoscopic classification of gastric ulcer].

PMID- 11979791
TI  - [Symptoms of peptic ulcer and their relationship to Helicobacter pylori
      infection].

PMID- 11979792
TI  - [Radiographic diagnosis of peptic ulcers].

PMID- 11979793
TI  - [Epidemiology in peptic ulcer].

PMID- 11979794
TI  - [Endoscopic diagnosis of peptic ulcer].

PMID- 11979795
TI  - [Diagnosis of peptic ulcers by endoscopic ultrasonography].

PMID- 11979796
TI  - [Endoscopic diagnosis of Helicobacter pylori infection].

PMID- 11979797
TI  - [Histological diagnosis of Helicobacter pylori infection].

PMID- 11979798
TI  - [Diagnosis of Helicobacter pylori infection by culture method].

PMID- 11979799
TI  - [Diagnosis of Hlicobacter pylori infection by PCR].

PMID- 11979800
TI  - [Serodiagnosis of Helicobacter pylori infection].

PMID- 11979801
TI  - [Serological diagnosis of Helicobacter pylori infection].

PMID- 11979802
TI  - [Urea breath test for diagnosis of Helicobacter pylori infection].

PMID- 11979803
TI  - [Detection methods of antibodies to Helicobacter pylori in urine].

PMID- 11979804
TI  - [Epidemiology of peptic ulcer].

PMID- 11979805
TI  - [Diagnosis of Helicobacter pylori infection by the antigen analysis of stools].

PMID- 11979806
TI  - [Drug sensitivity test for Helicobacter pylori].

PMID- 11979807
TI  - [Complication of peptic ulcer disease].

PMID- 11979808
TI  - [The outline of medical treatment of peptic ulcer].

PMID- 11979809
TI  - [Current role of acid suppressants in the treatment of peptic ulcer disease].

PMID- 11979810
TI  - [New therapeutic approaches to peptic ulcer using mucosal protective agents].

PMID- 11979811
TI  - [Prokinetics of gastrointestinal system; its newer aspects with regard to
      motillity stimulants].

PMID- 11979812
TI  - [The foreign guidelines for the management of Helicobacter pylori infection].

PMID- 11979813
TI  - [Guidelines for the management of Helicobacter pylori infection in Japan].

PMID- 11979814
TI  - [Epidemiology of H. pylori infection].

PMID- 11979815
TI  - [Guidelines of Helicobacter pylori eradication in children].

PMID- 11979816
TI  - [Indication of H. pylori eradication therapy].

PMID- 11979817
TI  - [New triple therapy for Helicobacter pylori infection].

PMID- 11979818
TI  - [Classic triple therapy for Helicobacter pylori infection].

PMID- 11979819
TI  - [Dual therapy for Helicobacter pylori resistance to anti microbial agents].

PMID- 11979820
TI  - [Application of national health insurance].

PMID- 11979821
TI  - [Proton pump inhibitor-based quadruple therapy regimen for Helicobacter pylori
      infection].

PMID- 11979822
TI  - [Effect of PPI/AM re-treatment regimen for the patients with Helicobacter pylori
      infection after failure of first line eradication therapy by PPI/AC regimens].

PMID- 11979823
TI  - [High dose dual PPI/AMPC therapy for the treatment of Helicobacter pylori
      infection after failure of usual standard triple PPI/AMPC/CAM therapy: CYP2C19
      polymorphism].

PMID- 11979824
TI  - [Second line treatment regimen of PPI + AMPC + MNZ for patients with
      clarithromycin-resistant Helicobacter pylori infection].

PMID- 11979825
TI  - [Minocycline-containing eradication therapy for patients with clarithromycin
      resistant Helicobacter pylori infection].

PMID- 11979826
TI  - [Triple therapy with faropenem, proton pump inhibitor (PPI), and amoxicillin for
      clarithromycin-resistant H. pylori eradication].

PMID- 11979827
TI  - [Ecabet sodium (ECA) + PPI + AMPC therapy for clarithromycin-resistant
      Helicobacter pylori infections].

PMID- 11979828
TI  - [Eradication therapy for clarithromycin-resistant and metronidazole-resistant
      Helicobacter pylori infection].

PMID- 11979829
TI  - [Adverse effects of H. pylori eradication therapy and its measure].

PMID- 11979830
TI  - [Acute mucosal lesion of the upper-gastrointestinal tract observed after H.
      pylori-eradication].

PMID- 11979831
TI  - [GERD after H. pylori eradication therapy].

PMID- 11979832
TI  - [Intractable ulcer after the eradication of Helicobacter pylori].

PMID- 11979833
TI  - [H. pylori eradication therapy and natural history of peptic ulcer].

PMID- 11979834
TI  - [Analysis of H. pylori eradicated patients during more-than-5-year follow-up].

PMID- 11979835
TI  - [Long-term effect of H. pylori eradication on quality of life].

PMID- 11979836
TI  - [History of peptic ulcer research].

PMID- 11979837
TI  - [The analysis of the recurrence ulcer after H. pylori eradication].

PMID- 11979838
TI  - [Diagnosis of H. pylori infection].

PMID- 11979839
TI  - [Economic evaluation of Helicobacter pylori eradication for peptic ulcer disease
      in comparison with a conventional strategy in Japan].

PMID- 11979840
TI  - [Maintenance treatment after success of H. pylori eradication].

PMID- 11979841
TI  - [Continuation of acid suppression therapy after H. pylori eradication].

PMID- 11979842
TI  - [Endoscopic technique for hemostasis of peptic ulcer hemorrhage].

PMID- 11979843
TI  - [Surgical therapy for peptic ulcers].

PMID- 11979844
TI  - [Epidemiology of NSAIDs ulcer].

PMID- 11979845
TI  - [Inhibitory factors for healing of NSAIDs-induced ulcers].

PMID- 11979846
TI  - [Clinical finding of NSAIDs associated gastric ulcer].

PMID- 11979847
TI  - [Treatment of NSAIDs induced ulcers].

PMID- 11979848
TI  - [Pathogenesis of peptic ulcers: Gastric acid secretion update].

PMID- 11979849
TI  - [Chaperon-induction therapy for peptic ulcers].

PMID- 11979850
TI  - [Prophylaxis against non-steroidal anti-inflammatory drug-associated ulcers and
      erosions].

PMID- 11979851
TI  - [Intractable ulcer].

PMID- 11979852
TI  - [Stomal ulcer].

PMID- 11979853
TI  - [Dieulafoy's ulcer].

PMID- 11979854
TI  - [Gastroduodenal ulcer in childhood].

PMID- 11979855
TI  - [Peptic ulcer in the elderly].

PMID- 11979856
TI  - [GERD/reflux esophagitis].

PMID- 11979857
TI  - [Zollinger-Ellison syndrome].

PMID- 11979858
TI  - [Stress ulcer].

PMID- 11979859
TI  - [Role of proton pump inhibitors in the eradication therapy for Helicobacter
      pylori (overviews)].

PMID- 11979860
TI  - [Proton pump inhibitors: Omeprazole].

PMID- 11979861
TI  - [Pathogenesis of peptic ulcers: New aspects of gastric mucosal defense].

PMID- 11979862
TI  - [Proton pump inhibitors: Efficacy of lansoprazole in eradicating Helicobacter
      pylori].

PMID- 11979863
TI  - [Proton pump inhibitors: Rabeprazole].

PMID- 11979864
TI  - [Proton pump inhibitors: Tenatoprazole (TU-199)].

PMID- 11979865
TI  - [Proton pump inhibitors: Pantoprazole].

PMID- 11979866
TI  - [Amoxicillin (AMPC)].

PMID- 11979867
TI  - [Clarithromycin (CAM)].

PMID- 11979868
TI  - [Metronidazol (MNZ)].

PMID- 11979869
TI  - [The role of H2RA in the eradication therapy of Helicobacter pylori].

PMID- 11979870
TI  - [Mucosal protective factor; role in the 'H. pylori age'].

PMID- 11979871
TI  - [Sucralfate].

PMID- 11979872
TI  - [Pathogenesis of peptic ulcers: Genetics of H. pylori].

PMID- 11979873
TI  - [Plaunotol].

PMID- 11979874
TI  - [Rebamipide].

PMID- 11979875
TI  - [Sofalcone].

PMID- 11979876
TI  - [Ecabet sodium].

PMID- 11979877
TI  - [Polaprezinc].

PMID- 11979878
TI  - [Role of prostaglandin analog in eradication of Helicobacter pylori].

PMID- 11979879
TI  - [H. pylori-infected Mongolian gerbil model].

PMID- 11979880
TI  - [Japanese monkey model of Helicobacter pylori].

PMID- 11979881
TI  - [Bacteriology of H. pylori].

PMID- 11979882
TI  - [Current progress in the development of prophylactic and therapeutic vaccination
      against H. pylori infection].

PMID- 11979883
TI  - [Prospect of the development of new bactericidal drugs against Helicobacter
      pylori for eradication therapy].

PMID- 11979884
TI  - [Probiotics for H. pylori infection].

PMID- 11979885
TI  - [A new problem after Helicobacter pylori eradication 'obesity'].

PMID- 11979886
TI  - [Effects of H. pylori eradication on the risk factors for cardiovascular event].

PMID- 11979887
TI  - [Non-ulcer dyspepsia and H. pylori].

PMID- 11979888
TI  - [Cause and prevention of nocturnal gastric acid breakthrough].

PMID- 11979889
TI  - [CRHP (clarithromycin-resistant H. pylori) infection in children].

PMID- 11979890
TI  - [Helicobacter heilmannii-associated gastritis].

PMID- 11979891
TI  - [Perspectives in treatment of peptic ulcer disease].

PMID- 11979892
TI  - [H. pylori and its adhesion molecules].

PMID- 11979893
TI  - [Helicobacter pylori vacuolating cytotoxin (VacA) and its mode of action].

PMID- 11979894
TI  - [The relationship between anti-VacA antibody titer and atrophic gastritis].

PMID- 11979895
TI  - [Polymorphisms of vitamin D receptor gene].

PMID- 11979896
TI  - [Estrogen receptor gene polymorphism].

PMID- 11979897
TI  - [Association of beta 3-adrenergic receptor (beta 3-AR) gene polymorphism with
      bone mineral density].

PMID- 11979898
TI  - [Epidemiology of osteoporosis in Japan and western countries].

PMID- 11979899
TI  - [Advancement of treatment for osteoporosis].

PMID- 11979900
TI  - [Epidemiology on bone mineral density among Japanese women].

PMID- 11979901
TI  - [Natural history of osteoporosis--general review].

PMID- 11979902
TI  - [Back pain and its related physical findings in spinal osteoporotic patients].

PMID- 11979903
TI  - [Clinical diagnosis of vertebral fractures in osteoporosis].

PMID- 11979904
TI  - [Bone densitometry: its clinical application and current status].

PMID- 11979905
TI  - [Cross calibration of results measured with various bone mass measurement
      equipments].

PMID- 11979906
TI  - [Photodensitometry].

PMID- 11979907
TI  - [X-ray absorptiometry].

PMID- 11979908
TI  - [Quantitative ultrasound in the calcaneus].

PMID- 11979909
TI  - [Peripheral quantitative computed tomography].

PMID- 11979910
TI  - [Analysis of trabecular structure using micro--CT].

PMID- 11979911
TI  - [Biochemical markers for bone metabolism--overview].

PMID- 11979912
TI  - [Biochemical basis of bone resorption markers].

PMID- 11979913
TI  - [Bone formation markers].

PMID- 11979914
TI  - [Bone resorption marker].

PMID- 11979915
TI  - [New biochemical markers of bone turnover].

PMID- 11979916
TI  - [Recent advances in basic research of bone metabolism].

PMID- 11979917
TI  - [Biochemical markers of bone turnover for treatment of osteoporosis].

PMID- 11979918
TI  - [Diagnostic criteria and differential diagnosis for primary osteoporosis].

PMID- 11979919
TI  - [Treatment of osteoporosis: overview].

PMID- 11979920
TI  - [Guideline for treatment of osteoporosis].

PMID- 11979921
TI  - [Comparative analyses on osteoporosis guidelines in Japan, EU and USA].

PMID- 11979922
TI  - [Advance in the treatment of postmenopausal osteoporosis].

PMID- 11979923
TI  - [Treatment of male osteoporosis].

PMID- 11979924
TI  - [Osteoporosis in childhood].

PMID- 11979925
TI  - [Vitamin D in the treatment of osteoporosis].

PMID- 11979926
TI  - [Estrogen in the treatment of osteoporosis].

PMID- 11979927
TI  - [Bone remodeling].

PMID- 11979928
TI  - [Vitamin K2 in the treatment of osteoporosis].

PMID- 11979929
TI  - [Bisphosphonates: pharmacology and use in the treatment of osteoporosis].

PMID- 11979930
TI  - [Ipriflavone in the treatment of osteoporosis].

PMID- 11979931
TI  - [Androgen in the treatment of osteoporosis ].

PMID- 11979932
TI  - [Alendronate in the treatment of osteoporosis].

PMID- 11979933
TI  - [Surgical treatment for fracture with osteoporosis].

PMID- 11979934
TI  - [Nutritional therapy for patients with osteoporosis].

PMID- 11979935
TI  - [Recent advances in research on bone formation--BMP action and its mechanism].

PMID- 11979936
TI  - [Steroid-induced osteoporosis].

PMID- 11979937
TI  - [Bone destruction and bone loss in rheumatoid arthritis--mechanism, prevention
      and treatment].

PMID- 11979938
TI  - [Disuse osteoporosis].

PMID- 11979939
TI  - [Hypogonadism and osteoporosis].

PMID- 11979940
TI  - [Renal osteodystrophy: bone disease with renal disease].

PMID- 11979941
TI  - [Bone changes in primary hyperparathyroidism].

PMID- 11979942
TI  - [Osteoporosis in patients with thyroid disease].

PMID- 11979943
TI  - [Diabetic osteoporosis].

PMID- 11979944
TI  - [Hepatic osteodystrophy].

PMID- 11979945
TI  - [Assessment of health related quality of life in osteoporotic patients].

PMID- 11979946
TI  - [Recent advances in research of bone resorption].

PMID- 11979947
TI  - [Spinal deformity and disturbance of activity of daily life].

PMID- 11979948
TI  - [Diseases complicated with kyphosis].

PMID- 11979949
TI  - [Complications with the aged persons bed-bound after fracture].

PMID- 11979950
TI  - [Drugs in development for the treatment of osteoporosis: Active vitamin D
      analog(ED-71)].

PMID- 11979951
TI  - [Risedronate: clinical usage].

PMID- 11979952
TI  - [Drugs in development for the treatment of osteoporosis: Incadronate].

PMID- 11979953
TI  - [PTH injection for the treatment of osteoporosis].

PMID- 11979954
TI  - [Drugs in development for the treatment of osteoporosis: Tibolone].

PMID- 11979955
TI  - [Calcium-sensing receptor in bone cells].

PMID- 11979956
TI  - [Drugs in development for the treatment of osteoporosis:Raloxifene].

PMID- 11979957
TI  - [Prevention of osteoporosis by exercise].

PMID- 11979958
TI  - [Preventive nutrition of osteoporosis].

PMID- 11979959
TI  - [Prevention of fall and fracture].

PMID- 11979960
TI  - [Hip fracture prevention using hip protectors].

PMID- 11979961
TI  - [Community health promotion and education to prevent osteoporosis].

PMID- 11979962
TI  - [Health examination of osteoporosis by the local government].

PMID- 11979963
TI  - [The results of treatment in the osteoporosis dock--follow up for 9 years].

PMID- 11979964
TI  - [Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase].

PMID- 11979965
TI  - [Cost-effectiveness of the treatment for osteoporosis].

PMID- 11979966
TI  - [Policy for health promotion and welfare relating to osteoporosis in Japan].

PMID- 11979967
TI  - [Clinical applications of bone morphogenetic proteins].

PMID- 11979968
TI  - [Possible role of receptor activator of NF-kappa B ligand(RANKL) in osteoclast
      differentiation and function].

PMID- 11979969
TI  - [Osteoclastogenesis inhibitory factor (OCIF)/OPG (a novel therapeutic candidate
      for the treatment of metabolic bone diseases)].

PMID- 11979970
TI  - [Stimulation of bone formation by anti-hyperlipidemic agent statins and its
      mechanism of action].

PMID- 11979971
TI  - [Bioactive calcium phosphate paste injection for repair of vertebral fracture due
      to osteoporosis].

PMID- 11979972
TI  - [Recent advances in research on bone matrix proteins].

PMID- 11979973
TI  - [Recent progress of bone cell culture system (review)].

PMID- 11979974
TI  - [History of definition of osteoporosis].

PMID- 11979975
TI  - [Cbfa1/Runx2, an essential transcription factor for the regulation of osteoblast
      differentiation].

PMID- 11979976
TI  - [The study of the genetics of osteoporosis].

PMID- 11979977
TI  - [Strategies in chemotherapy against bacterial eye infections].

PMID- 11979978
TI  - [Antibiotic ophthalmic solutions evaluated by pharmacokinetic parameters of
      maximum concentration in the aqueous].
AB  - PURPOSE: In order to determine whether the one-component method for calculating
      drug concentration in the aqueous(AQCmax) is useful for selecting an appropriate
      ophthalmic solution, 6 general purpose antimicrobial ophthalmic solutions already
      on the market were investigated. METHODS: The drugs examined were levofloxacin
      (LVFX), chloramphenicol(CP), erythromycin lactobionate(EM), micronomicin
      sulfate(MCR), cefmenoxime hydrochloride(CMX) and disodium sufobenzyl
      penicillin(SBPC). Fifty microliters of each solutions was instilled into the cul
      de-sac of New Zealand White rabbit eyes 3 times at 15-minute intervals. The drug
      concentrations in(the anterior sac aqueous,: this is wrong) the aqueous humor 10,
      30, 60, 120 and 240 minutes after the final instillation were examined by high
      performance liquid chromatography(HPLC) and/or bioassay. The AQCmax was
      calculated using the one-compartment method. RESULTS: The calculated AQCmax was
      2.5 micrograms/ml (HPLC method) and 2.28 micrograms/ml (Bioassay Method) for
      LVFX, 2.17 micrograms/ml for CP, and 0.45 microgram/ml for EM. The AQCmax for
      CMX, MCR and SBPC could not be calculated by the one-compartment method.
      CONCLUSION: The AQCmax of LVFX was higher than that of the 2 other general
      purpose antimicrobial ophthalmic solutions. The AQCmax of these drugs might be a
      useful parameter for selecting an appropriate ophthalmic solution for the
      treatment of infected eyes.

PMID- 11979979
TI  - [Two families with primary open-angle glaucoma associated with myocilin gene
      mutations].
AB  - BACKGROUND: Myocilin is a gene that causes primary open-angle glaucoma(POAG). We
      found a family with normal tension glaucoma(NTG) whose members had an Asp 208 Glu
      mutation, and a family with POAG whose members had an Ile 360 Asn mutation in
      myocilin. CASE: In the family with the Asp 208 Glu mutation, the proband, a 31
      year-old male, was diagnosed as having NTG. His mother had the same mutation and
      was also diagnosed as having NTG, but a sister with the same mutation showed no
      glaucomatous changes. We also found this mutation in normal controls. In the
      family with the Ile 360 Asn mutation, the proband, a 67-year-old female, was
      diagnosed as having POAG. Four members of this family showed different phenotypes
      including POAG, ocular hypertension, and normal. We found no cases with the same
      mutation in the controls. CONCLUSION: Since the Asp 208 Glu mutation was found in
      NTG, the pathogenesis of glaucoma with myocilin mutation might be more complex
      and it may be related to weakness of the optic nerve head. On the other hand, the
      mutation may be a polymorphism. The Ile 360 Asn mutation was considered to be
      disease-causing. However, both late-onset glaucoma cases and non-glaucomatous
      cases were observed in this family. The implications of the mutation and other
      risk factors remain to be discussed.

PMID- 11979980
TI  - [Evaluation of ophthalmic visicoelastic devices in rabbit penetrating
      keratoplasty--the protective effect for corneal endothelial cells after
      autokeratoplasty and the effect of intraocular pressure after aqueous exchange].
AB  - PURPOSE: To investigate the effect of sodium hyaluronate molecular weight on
      corneal endothelial cells and intraocular pressure after penetrating keratoplasty
      in rabbits. MATERIAL AND METHOD: Rotating autokeratoplasty was carried out on
      rabbits using six groups of sodium hyaluronate in which the molecular weight
      differed. Then the endothelial cell density, hexagonal cell rate, corneal
      thickness, and intraocular pressure were measured. The intraocular pressure in
      the rabbit eyes after aqueous exchange with six groups of sodium hyaluronate was
      also measured. RESULTS: The endothelial cell density and hexagonal cell rate in
      the hyaluronate group of molecular weight 1.53-2.13 million and 1.9-3.9 million
      were the same as in the eye groups receiving no manipulation. As for the
      intraocular pressure after aqueous exchange, the highest intraocular pressure was
      more than 40 mmHg in the group treated with hyaluronate over 1.9 million and the
      group treated with hyaluronate and chondroitin sulfate compounding agent.
      CONCLUSION: Endothelial protection was considered to be superior when hyaluronate
      with a molecular weight of 1.5-3.9 million was used in rabbits. However, it is
      grossible that leaving a large amount of hyaluronate with a molecular weight over
      1.9 million in the eye may lead to a remarkable increase in the early
      postoperative intraocular pressure.

PMID- 11979981
TI  - [The correlation between retinal circulation and function in branch retinal
      artery occlusion].
AB  - PURPOSE: To investigate retinal circulation and function in eyes with branch
      retinal artery occlusion(BRAO) using a scanning laser Doppler flow-meter (SLDF)
      and multifocal electroretinogram (mERG). METHODS: In juxtapapillary and
      paramacular areas close to the occluded artery of the affected eye and the
      corresponding area of the fellow eye, the mean flow measured by SLDF, indicating
      microcirculation, and the p-wave amplitude in the response of mERG, indicating
      retinal function, were determined in three patients with BRAO at the period of
      reperfusion. The ratios of the affected eye to fellow eye(a/f ratio) were
      calculated, and the ratios of the mean flow (Fa/f) were compared with those of
      the p-wave amplitude(Pa/f). RESULTS: In the juxtapapillary area, both Fa/f and
      Pa/f decreased consistently, but in the paramacular area, Pa/f were lower than
      Fa/f in all cases. CONCLUSIONS: Functional recovery is likely to be later in the
      paramacular area than in the juxtapapillary area in the course of recovery of
      retinal circulation.

PMID- 11979982
TI  - [Quantitative analysis of indocyanine green angiography in multifocal posterior
      pigment epitheliopathy and its related diseases].
AB  - PURPOSE: To clarify the indocyanine green(ICG) angiographic features in
      multifocal posterior pigment epitheliopathy(MPPE), we measured the maximum
      diameter of the choroidal vein and mean fluorescence intensity within the
      vascular arcade. METHODS: ICG angiography was performed in 40 eyes of 20 patients
      with MPPE and 10 age-matched normal controls, and quantified by IMAGEnet.
      RESULTS: The mean maximum choroidal venous diameter was 544 +/- 162(mean +/-
      standard deviation) microns in eyes with MPPE and 278 +/- 55 microns in healthy
      age-matched control eyes. The mean fluorescence intensity was 106.9 +/- 52.5 and
      86.5 +/- 32.5, respectively. Both the mean maximum choroidal venous diameter and
      the mean fluorescence intensity showed statistical difference between the two
      groups. In contrast, there was no statistically significant difference between
      the eyes with serous retinal detachment and without detachment in the MPPE group.
      CONCLUSIONS: These results show that choroidal venous dilation and choroidal
      hyperfluorescence in MPPE are clearly distinguished from choroidal aging changes.
      Additionally, these pathological angiographic changes seemingly do not delineate
      the activity of MPPE, but demonstrate the background factor of the pathogenesis
      of MPPE.

PMID- 11979983
TI  - [Birdshot chorioretinopathy--a case report and a case study in Japanese
      patients].
AB  - PURPOSE: There have been numerous case reports of birdshot chorioretinopathy(BC)
      from Europe and USA. However, only 10 cases of BC have been reported in Japan. We
      report the case of a Japanese patient with BC and review the clinical
      characteristics of BC among Japanese patients previously reported. PATIENTS AND
      METHODS: We report the case of a 64-year-old Japanese man, who was seen at our
      clinic and then diagnosed as hasing BC. 20 eyes of 11 patients with BC reported
      in the Japanese literature previously, including our patient, were studied. Age
      at the initial onset, sex, ocular findings, prognosis of visual acuity and the
      human leucocyte antigen (HLA) were evaluated. RESULTS: In our case bilateral
      cream-colored subretinal exudates presented symmetrically and in time developed
      depigmented atrophic 'birdshot like' scar lesions. Ocular inflammation responded
      to oral prednisolone without exacerbation and good visual acuity was maintained.
      The age at the onset ranged from 19 to 78 years(mean 54.5), and 8 patients were
      women. Cystoid macular edema(CME) was found in 30% of 11 Japanese patients, and
      optic disc edema was seen in 50%. Final visual acuity was more than 20/40 in 75%
      and less than 20/200 in 12.5% of the cases. HLA-A 29, which is frequently
      associated with Caucasian patients, was not positive in any of the Japanese
      patients, and no specific locus was determined. CONCLUSIONS: We observed a rare
      case of BC. Age at initial onset, sex, and ocular findings of Japanese patients
      with BC were consistent with those of Europe and the US and good visual acuity
      was maintained in almost all cases. We suggest that the disease mechanism of BC
      in Japanese patients is different from that of Caucasian patients, because HLA-A
      29 was negative in all Japanease patients.

PMID- 11979984
TI  - [A macular hole in the eye of a young patient with retinitis pigmentosa].
AB  - PURPOSE: To describe the histological and cytological findings in the epiretinal
      membrane around a macular hole. CASE: A 24-year-old male patient with retinitis
      pigmentosa had had night blindness since childhood. A macular hole(Stage 2) in
      his left eye was noted when he was 18 years old. He visited our department when
      he was 22 years old. The visual acuity on the left was 0.5 at the first
      examination and two years later it was 0.2 with enlargement of the macular hole.
      Pars plana vitrectomy was applied, and we removed the thick yellow epiretinal
      membrane around the hole. The macular hole was closed, and the visual acuity
      improved to 0.7. The removed membrane contained many cells including macrophages,
      Muller cells, glial cells, and fibroblasts. There were many granules that
      appeared to be xantophyll outside the cell bodies. CONCLUSION: The components of
      the membrane suggest that the macular hole was caused by vitreous degeneration
      due to retinitis pigmentosa.

PMID- 11979985
TI  - Introduction to an alternate view of acid/base balance: the strong ion difference
      or Stewart approach.
AB  - The carbonic acid/bicarbonate system, as defined by the Henderson-Hasselbach (H
      H) equation, has traditionally formed the centrepiece of the presentation of
      acid/base physiology in nursing education. However, an alternative approach to
      describe acid/base physiology was proposed by Peter Stewart in 1983. Stewart
      determined, using the physiochemical principles of dissociation equilibrium,
      electroneutrality and conservation of mass, that hydrogen ion concentration [H+]
      was dependent upon the difference between the concentrations of strong cations
      and strong anions in a solution (the strong ion difference or SID), concentration
      of weak acid anions, and the partial pressure of carbon dioxide in plasma.
      Therefore, a change in pH (the [H+] expressed as its negative log) indicates that
      there must be a change in one of these independent variables, and not simply
      explained by movement of hydrogen ions or bicarbonate into or out of the body
      fluids. An analysis of the complex acid/base derangements commonly seen in the
      critically ill can be achieved using this approach. The acid/base consequences of
      vomiting, gastric aspiration, diarrhoea, diuretic therapy, the infusion of large
      volumes of normal saline, the contribution of lactate, and the effects of
      methanol and ethylene glycol poisoning can all be more readily understood
      considering Stewart's explanation of acid/base balance. This paper outlines this
      alternative approach and provides some examples for the intensive care setting.

PMID- 11979986
TI  - Health status of ICU survivors: a pilot study.
AB  - This paper reports on a pilot study that focused on the feasibility of conducting
      longitudinal research on the health status of intensive care unit (ICU)
      survivors. Twenty patients completed a short ICU specific health status survey
      while in ICU and then were invited to complete the same survey--with the addition
      of the Medical Outcome Study Short Form-36 (SF-36) health status survey--at 6 and
      12 months after their hospital discharge. While the patients were in the ICU, 20
      family members completed the same survey on the patients' behalf as proxy
      respondents. Most patients were willing to be in the study for its duration.
      There was a wide variation in patients' responses to the ICU specific instrument
      at all data collection points. Patient and proxy responses were very similar for
      almost all of the physical items but there was a lack of agreement for the more
      subjective psychosocial items. The SF-36 was found to be more reliable and easier
      to score and analyse in this small study than the ICU specific health status
      instrument. The three SF-36 scales ranked lowest at 6 months were physical
      functioning, role-physical and role-emotional, while at 12 months the three
      lowest were role-physical, role-emotional and vitality. Total attrition at 12
      months was 40 per cent. Using the results of the SF-36, sample size estimates
      were conducted in preparation for a larger study. It was concluded that it is
      feasible to conduct longitudinal research on ICU survivors but proxy responses
      should not be used indiscriminately.

PMID- 11979987
TI  - Why families deny consent to organ donation.
AB  - Advances in medical practice and technology and the success of organ
      transplantation over the past 2 decades have resulted in an increased demand for
      organ donors. However, the health care community and organ procurement
      organisations (OPO) are faced with a worldwide shortage of donor organs. The non
      consent of families is the most common reason that organs of medically suitable
      potential donors are not recovered. A review of published research post 1990 was
      conducted to primarily determine the major factors that influence a family's
      decision to deny consent to donation. Other objectives included providing
      suggestions for health care personnel to facilitate the donation request
      experience and to suggest strategies that would increase donation consent rates
      to benefit the organ procurement process. Databases predominately used in the
      review included CINAHL and Medline. The world wide web (www) was also accessed.
      The literature review indicates that the significant factors associated with
      denial of consent include: the misunderstanding of brain death; cultural beliefs;
      the specific timing of the request; the setting in which the request is made; the
      approach of the individual making the request; and characteristics of the
      deceased. Organ donation and transplantation rates could be increased by the
      joint involvement of medical, nursing and OPO personnel to enhance the quality of
      hospital care and to ensure that requests for donation are handled in a way that
      meets the family's informational and emotional needs. Increased consent rates
      have the potential to save lives and improve the quality of life for organ
      recipients.

PMID- 11979988
TI  - Of armoured personnel carriers and magic bullets.

PMID- 11979989
TI  - Effect of support programme to reduce stress in spouses whose partners 'fall off'
      clinical pathways post cardiac surgery.
AB  - Cardiac surgery is flourishing in today's health care industry and looks to
      prosper well into the future. More than ever, improved technology, surgical skill
      and the worldwide trend of increasing longevity means that surgical intervention
      is offered to patients rarely seen in cardiac units in previous years. Patients
      are now much older, with multiple co-morbidity including repeat cardiac surgery.
      In line with advances in cardiac surgery, critical pathways to map the expected
      recovery route for the patient have been introduced. These maps are used
      extensively as guides for treatment and care. It is not only health professionals
      who use the pathways; patients and their relatives also refer to them as
      indicators of a 'normal' post-operative route. As a result, the critical pathway
      provides an avenue for expectations of predicted progress through to discharge.
      These predictors appear to give spouses hope, access to earliest possible
      visitation and confidence in a positive outcome. Nevertheless, it has recently
      become increasingly clear that for partners of patients who fail to proceed as
      expected, who apparently 'fall off' the predicted road to recovery, the critical
      pathway is problematic. Partners of such patients tend to demonstrate greatly
      heightened anxiety and nurses often have to deal with them at the point of
      crisis. In the cardio-thoracic unit at which this study was undertaken, the
      significant number of spouses who ended up in crisis drew attention to the need
      for additional support to be built into the post open-heart surgery critical
      recovery pathway. This study sought therefore to examine how nurses might assist
      spouses to adapt in the event of a complicated recovery following bypass surgery.
      A convenience sample of 39 spouses of cardiac surgical patients admitted to the
      cardio-thoracic recovery unit was obtained to assess stress responses at a
      critical post-operative data point, 5 days post-surgery. A symptoms of stress
      inventory was used to measure 94 items of physiological stress in 10 specific
      subscale categories. As a result of this study, it was found that incorporating a
      spousal support programme into the critical pathway of open-heart surgical
      patients significantly reduced stress suffered by spouses of patients who
      deviated from pre-determined recovery goals. The findings suggest that nurses
      need to understand the implications of the critical pathway and provide families
      with information concerning issues associated with complicated recovery. An
      unexpected finding of the study pointed to an apparent difference in the stress
      experienced by male spouses to that of female spouses. Recommendations from this
      study are to further explore the qualitative component of the stress felt by
      spouses and the negative association of stress with morbidity and mortality for
      women and patients without spouses. Nurses need to consider developing and
      implementing a stress management programme for spouses, establishing spousal
      support groups and exploring the possibility of incorporating spousal support
      strategies into the critical pathways of patients across hospital settings.

PMID- 11979990
TI  - Considering the needs of families in the critical care environment.

PMID- 11979991
TI  - Data clarification.

PMID- 11979992
TI  - Position statement on intensive care nursing staffing.

PMID- 11979993
TI  - Monitoring gaseous exchange: implications for nursing care.
AB  - The purpose of this study is to examine whether a relationship exists between
      arterial and end-tidal carbon dioxide tension (PaCO2 and PETCO2 respectively) in
      patients admitted to intensive care units (ICUs), and what the implications it
      has for nursing care. PaCO2 and PETCO2 are indicators of ventilatory adequacy
      which is an important aspect of respiratory function. These measures of carbon
      dioxide tension are obtained via invasive and non-invasive monitoring tools.
      Measurement of PETCO2 has only recently been introduced into ICUs and its
      usefulness in these environments is open to debate. A population of 30 intubated
      patients had 214 simultaneous measurements of PaCO2 and PETCO2 taken over a
      period of 10 months. The findings indicate that, despite strong significant
      correlations, PETCO2 cannot be used safely as a substitute for PaCO2 as the
      arterial/end-tidal carbon dioxide gradient is not constant, nor does capnography
      provide a consistently reliable indicator of PaCO2.

PMID- 11979994
TI  - [Treatment of unstable coronary disease].
AB  - The clinical presentations of ischemic heart disease comprises the term of acute
      ischaemia syndromes, that include unstable angina pectoris, non-Q-wave myocardial
      infarction, Q-wave-myocardial infarction and sudden death. Among the different
      presentations of acute ischemic syndromes, the unstable angina and non-Q-wave
      myocardial infarction can be regarded together. In both pathologic entity, the
      plaque rupture, or erosion signifies the primary event, which is the source of
      the highly thrombogenic substances coming out from the core of the
      atherosclerotic plaque and entering to the coronary and systemic circulation.
      They cause a thrombocyte-rich "white" intracoronary thrombus, that is not fully
      obstructive, or there is adequate collateral circulation, being the pathogenetic
      substrate that prevents the development of transmural necrosis. The nosologically
      bound two clinical entity can be called as "unstable coronary artery disease"
      (UCAD), since they have uniform etiologic, risk stratification and therapeutic
      backgrounds and also therapeutic targets that are basically distinct, they are
      admitted for transmural "ST-elevation" infarction. The review is discussing the
      therapy and the questions of follow-up of the disease according to the guidelines
      of the European Society of Cardiology and to the multicenter evidence based
      studies.

PMID- 11979995
TI  - [Hepatitis C and immunoglobulin heavy-chain gene rearrangement].
AB  - Hepatitis C virus (HCV) has cytopathogenic effect not only on hepatocytes,
      however on salivary glands, monocytes of peripheral blood and lymphoid cells, may
      explain the systemic manifestations of the infection. HCV activates B and T
      cells, modifies the immune response, causes lymphoproliferation, leading the
      development of B-cell non-Hodgkin's lymphoma (NHL). In the majority of B-cell
      NHLs immunoglobulin heavy chain (IgH) and light chain (IgL) genes are rearranged
      and expressed on cell surface in the early stage of the ontogenesis. The analyses
      of IgH rearrangement prove the clonality of lymphoproliferative disorders giving
      a powerful approach to the B-cell origin identification of cell proliferation.
      PATIENTS AND METHODS: IgH gene rearrangements were examined from the sera of 57
      chronic HCV infected patients and 11 HCV-positive cryoglobulinemic patients as
      well. RESULTS: Cryoglobulinemia was detected in 20% of all chronic hepatitis C
      virus infected patients and IgH rearrangement was observed in 10.29% (7/68), 4/7
      patients (57.14%) suffered from cryoglobulinemia. CONCLUSIONS: These results
      support the hypothesis that IgH gene rearrangement in HCV positive patients can
      indicate the lymphoproliferative disorder in the HCV infection released B-cell
      proliferation and lymphoma development.

PMID- 11979996
TI  - [Surgical complications and their treatment options in total knee replacement].
AB  - INTRODUCTION: One of the most important achievements of modern orthopedics is the
      treatment of degenerative disorders of the knee joint with endoprostheses. The
      most often used type of knee prosthesis implanted in our times is the total
      condylar one. With increasing numbers of prosthesis operations the number of
      complications is also increasing. AIM: Knowledge of diagnostic and treatment
      principles of complications is important for all institutions applying knee
      prostheses. The aim of present study is to report the authors' experience with
      the most important surgical problems following knee arthroplasty.
      PATIENTS/METHODS: At the Department of Orthopedics of the University of Pecs
      between 1993 and 1999 344 primary total condylar prostheses were implanted. Based
      on their own cases, the authors show the most important surgical problems after
      total knee arthroplasty. RESULTS: In their patient sample they observed
      infections, patellofemoral complaints and supracondylar femoral fractures being
      the commonest complications. Besides these problems they faced with some rare
      ones, like instability of the artificial joint and temporary peroneal palsy.
      Probably because of the relatively short follow up period, the authors had to
      perform only one revision procedure due to aseptic mechanical problems. The
      incidence of the most common complications in the authors' patient material is
      described as well as the principles and results of the applied treatment methods.
      Own experiences are compared with data from the literature. CONCLUSIONS: Although
      knee arthroplasty complications can be variable and followed by serious
      consequences, even the most significant ones can be managed with methods which
      provide the option of healing and restoration of knee functions.

PMID- 11979997
TI  - [Infantile acute lobar nephritis].
AB  - INTRODUCTION: Acute lobar nephronia is a focal interstitial inflammation of the
      kidney healing well on conservative therapy. OBJECTIVE: Authors call attention on
      this rare pathological entity and emphasize the role of the imaging modalities in
      making the diagnosis. Short literature review is also given. PATIENT AND METHODS:
      An 11 months old babyboy presented with febrile seizure and palpable right flank
      mass. Abdominal sonography and CT were done. RESULTS: Urine analysis gave
      evidence of upper urinary tract infection. Hyperechogenic solid mass in the right
      kidney was seen on sonography. Diagnosis of infection suspected on sonography has
      been confirmed by abdominal CT scan and possibility of tumor has been ruled out.
      Acute lobar nephronia was diagnosed and the patient has been treated successfully
      with antibiotics. CONCLUSION: Acute lobar nephronia may mimic both abscess and
      tumor. Differential diagnosis is very important because treatment of acute lobar
      nephronia is nonsurgical.

PMID- 11979998
TI  - [Metabolic syndrome--definition, diagnostic criteria and screening].

PMID- 11979999
TI  - [Technique, indications, and results of "mini-percutaneous" nephrolithotomy].
AB  - In 1997, Jackman and Helal described a miniaturized PCNL technique in children
      using an 11 F introducer sheath: "mini-percutaneous" nephrolithotomy. Preliminary
      studies showed that the success rate of this new technique for stones less than
      20 mm diameter was comparable to that of standard PCNL. Jackman reported a
      success rate of 85% in children. In adults, using a 13 F sheath, Chan reported a
      success rate of 94% in 17 patients and Jackman reported a success rate of 92% in
      11 patients. With a 20 F sheath, Monga reported a success rate of 90% in 21
      patients. All authors emphasized the value of a small calibre sheath (11 to 20 F)
      to decrease the morbidity and parenchymal lesions associated with conventional
      PCNL. However, no randomized prospective study has compared the morbidity of the
      two types of access. The repercussions of "mini-percutaneous" nephrolithotomy and
      conventional PCNL (11 F versus 30 F) on the renal parenchyma were recently
      evaluated. No significant difference in terms of parenchymal scarring was
      demonstrated. The volume of damaged renal parenchyma represented less than 1% of
      the total volume for the two types of access. There is therefore no advantage to
      use a small calibre nephrolithotomy exclusively 2 to preserve the renal
      parenchyma. This article reviews this new technique, its indications and its
      results.

PMID- 11980000
TI  - [Seminal vesicle cyst with agenesis of homolateral kidney].
AB  - A case of seminal vesicle with ipsilateral renal agenesis is presented. In the
      light of this case, symptomatology, diagnosis and treatment option are discussed.

PMID- 11980001
TI  - [Dermoid cyst of the testis].
AB  - The authors report a case of a 30-year-old patient presenting with a right
      testicular mass. The presumptive diagnosis was that of a malignant tumour. The
      definitive diagnosis, confirmed by histological examination of the orchidectomy
      specimen, was that of a dermoid cyst. The aetiopathogenic, diagnostic and
      therapeutic characteristics of this exceptional disease are reported.

PMID- 11980002
TI  - [Diagnostic and therapeutic approach of angiomyolipoma].
AB  - Renal angiomyolipoma is a benign tumour, composed of three different tissue
      components: muscle, vascular and fat, with a variable distribution. The frequency
      of haemorrhagic changes of this type of lesion and the importance of the
      differential diagnosis with a malignant renal lesion, require the definition of
      an adapted diagnostic and therapeutic strategy, the major elements of which are
      discussed herein.

PMID- 11980003
TI  - [Role of uropontin in calcium oxalate lithogenesis].
AB  - The formation of calcium oxalate stones involves four phases: nucleation, growth,
      aggregation and retention. Stone formation is a complex, multifactorial
      phenomenon involving, among other factors, proteins, some of which play an
      inhibitory role, while others play a promoting role. The authors studied the role
      of uropontin. Uropontin is the urinary form of osteopontin. Osteopontin is
      essentially involved in the mineralisation of bone tissue. Uropontin is secreted
      in the kidney by epithelial cells of the distal convoluted tubule and loop of
      Henle. Uropontin has an inhibitory action on the four phases of calcium oxalate
      crystal formation and is also one of the main constituents of the calcium oxalate
      stone matrix. A reduction of uropontin expression in epithelial cells induces a
      reduction of calcium oxalate stone formation. Uropontin is a protein largely
      involved in the lithogenesis of urinary stones, but its mechanism of action has
      not yet been fully elucidated.

PMID- 11980004
TI  - [Practical impact of pharmacologic and clinical data on early post-operative
      instillation of mitomycin C].
AB  - The authors present the current pharmacological and clinical data concerning EPOI
      and their practical implications. The importance of performing this instillation
      during the first 24 hours following TURB appears to be confirmed. EPOI of MMC is
      accompanied by a 34 to 50% reduction of early recurrences. Data in the literature
      confirm the low systemic diffusion of MMC and good safety, under certain
      conditions. Computerized modelling of pharmacological data ensures optimal
      modalities of MMC instillations. Recent clinical data confirm the value of these
      measures. In view of the higher early recurrence rate for superficial multifocal
      and/or recurrent tumours, these modalities could be preferentially indicated in
      these cases. However, IPOP must be considered cautiously for very large tumours
      accompanied by deep resection and/or bladder perforation.

PMID- 11980005
TI  - [Mumps virus and orchitis: towards a physiopathologic approach].
AB  - Mumps orchitis is a dreaded complication of mumps is pubescent men. The
      literature on this subject includes epidemiological, clinical, histological and
      endocrine findings, indicating a marked variability of the clinical features from
      one patient to another, an alteration of endocrine function that can persist in
      the long term and finally post-mumps infertility, which is exceptional. On the
      other hand, relatively few studies have investigated the pathophysiological
      mechanisms, and suggest replication of the mumps virus in the testis. Based on
      these data from the literature, this article reviews or proposes various
      hypotheses concerning the various pathophysiological aspects of this disease and
      discusses the lines of research that could advance the current knowledge in order
      to improve the therapeutic management of patients, while also providing a better
      knowledge of the mumps virus and basic testicular physiology.

PMID- 11980006
TI  - [Penile reconstruction following amputation by electrocution].
AB  - We report a case of penile reconstruction after traumatic loss of the penis in a
      27-year old man who was electrocuted. Phalloplasty using the remaining stumps of
      the corpora cavernosa was performed. The functional and cosmetic aspects of the
      organ are good.

PMID- 11980007
TI  - [Could phimosis have been the cause of sexual difficulties and delayed fertility
      of Louis XVI (1754-1793)?].
AB  - The great majority of historians agree that the marriage of Louis XVI and Marie
      Antoinette was only consumated seven years after the official ceremony. This
      delay could have been due to a genital malformation (phimosis) of Louis XVI, a
      strict religious education, a traumatic childhood and the young age of the two
      spouses, factors that may have inhibited their sexuality. In this article, the
      authors try to determine whether Louis XVI was able to overcome his sexual
      difficulties following an operation (circumcision) or as a result of spontaneous
      cure.

PMID- 11980008
TI  - [The essential from the 95th congress of the French Association of Urology,
      November 14-17, 2001].

PMID- 11980009
TI  - [Rigid ureteroscopy in the case of suspected tumor of the upper urinary tract:
      report of 63 cases].
AB  - OBJECTIVE: This retrospective study was designed to determine the place of rigid
      ureteroscopy in the diagnosis of upper urinary tract tumours. MATERIAL AND
      METHODS: 63 patients (45 males and 18 females) with a mean age of 60 years, were
      investigated by rigid ureteroscopy for suspected upper urinary tract tumour. The
      Wolf 8-9.8 F ureteroscope was used in the case of suspected upper urinary tract
      tumour in a context of ureteric obstruction on the IVU in 29 cases, haematuria in
      23 cases, a defect on retrograde ureteropyelography in 5 cases, suspicious CT
      scan in 5 cases and positive cytology with normal cystoscopy in 2 cases. RESULTS:
      The ureteroscope was able to be advanced as far as the suspicious zone in 89% of
      cases. The mean operating time was 48 minutes and the mean hospital stay was 3.2
      days. Diagnostic rigid ureteroscopy has a Sensitivity of 58% (95% confidence
      interval CI95: +/- 28), a Specificity of 100%, a Positive Predictive Value of
      100%, a Negative Predictive Value of 91% (+/- 7) and a low morbidity (3%).
      CONCLUSION: Rigid ureteroscopy does not appear to be the examination of choice
      for the diagnosis of upper urinary tract tumours, as it cannot investigate the
      renal pelvis or calices and the ureteroscope cannot always be advanced to the
      suspicious zone. The flexible ureteroscope now appears to be a more reliable
      diagnostic tool.

PMID- 11980010
TI  - [Post-traumatic secondary arteriovenous fistulae of the kidney and their
      embolization. Report of 3 cases].
AB  - INTRODUCTION: Non-iatrogenic post-traumatic arteriovenous fistulas of the kidney
      raise a diagnostic and especially therapeutic problems. The authors report their
      experience based on 3 cases of arteriovenous fistulas treated by selective
      embolization during diagnostic arteriography. MATERIALS AND METHOD: In a series
      of 18 patients urgently admitted to hospital for kidney trauma during 2000, 3
      patients presented a secondary arteriovenous fistula diagnosed on arteriography.
      All patients were initially treated by surveillance in the surgical ward. The
      diagnosis of arteriovenous fistula was subsequently suspected following
      recurrence of haematuria with a moderate fall in haemoglobin in two cases, and
      secondary appearance of lumbar pain without anaemia in the third case. For the
      two patients with secondary haematuria, arteriography demonstrated an
      arteriovenous fistula associated with an arterio-caliceal fistula. For the last
      patient, Doppler ultrasound suggested the diagnosis of arteriovenous fistula,
      which was confirmed by the arteriography. RESULTS: Selective embolization by
      "coils" and particle was performed during arteriography and ensured closure of
      the fistulas in every case. The postoperative course was uneventful for all three
      patients. With a mean follow-up of 7 months, no recurrence of the fistula has
      been observed. The remaining renal parenchyma is functional with preservation of
      renal function. CONCLUSION: The risk of arteriovenous fistula must be kept in
      mind in any case of lumbar trauma. Arteriography with selective embolization
      allows good control of these secondary fistulas while preserving a maximum of
      functional renal parenchyma, and therefore appears to be the treatment of choice
      of this complication.

PMID- 11980011
TI  - [T1 bladder tumors: value of a second endoscopic resection].
AB  - OBJECTIVE: To quantify the percentage of residual tumour following systematic
      second endoscopic resection of pT1 bladder tumours before starting treatment with
      intravesical instillations and to definitively exclude muscle invasion. MATERIAL
      AND METHODS: From January 1995 to December 1999, 52 patients with a first
      diagnosis of pT1 bladder tumour underwent a second endoscopic resection 3 to 5
      weeks later. Nine surgeons, 5 seniors and 4 juniors, managed these patients and
      the initial resection was considered to be complete in every case. The second
      resection consisted of resection of the initial tumour bed and distant biopsies
      either directed to zones of suspicious CIS zones or quadrant biopsies in the case
      of optically healthy mucosa. RESULTS: Of the 52 included patients, 19 (36.5%) had
      residual disease on the second endoscopic resection. Pathological staging was:
      pT0 = 63.5% (33 patients), pTa = 11.5% (6 patients), pTis = 3.85% (2 patients),
      pT1 = 17.3% (9 patients), > or = pT2 = 3.85% (2 patients). Residual tumour tissue
      was revealed at the resection site in 84.2% of cases and in another site in 15.8%
      of cases. Residual tumour was significantly more frequent in the case of
      multifocal tumour than in the case of solitary tumour (57.9% vs 24.23%), and when
      managed by a junior surgeon compared to a senior surgeon (53.8% vs 30.8%).
      CONCLUSION: This second endoscopic procedure appears to be essential to ensure
      the absence of residual tumour before starting conservative treatment for pT1
      bladder tumours.

PMID- 11980012
TI  - [Main grade of Gleason's 7 score of the surgical sample correlated with biologic
      progression in patients treated for total prostatectomy].
AB  - OBJECTIVES: To analyse the influence of the main grade of Gleason score 7 of the
      operative specimen correlated with the blood PSA level on the laboratory
      progression-free survival of patients treated by radical prostatectomy. MATERIALS
      AND METHODS: 331 patients consecutively treated by radical prostatectomy and
      presenting a Gleason score 7 were analysed. Exclusion criteria were the use of
      radiotherapy and/or preoperative and/or postoperative endocrine therapy. The main
      grade (3 or 4), histological stage, and blood PSA level were analysed for their
      predictive value of laboratory progression-free survival. The mean follow-up was
      3.5 years (range: 13.6 to 72.8 months). Laboratory recurrence was defined by a
      PSA > 0.4 ng/ml. RESULTS: The main grade of Gleason score 7 was 3 in 199 (60%)
      patients and 4 in 132 (40%) patients with a mean follow-up of 3.6 years.
      Laboratory progression-free survival rates were 89% and 72% for main grades 3 and
      4, respectively (p = 0.03). When the cancer was confined to the prostate, the
      progression-free survival rates were 96% and 88% for main grades 3 and 4,
      respectively (p = 0.01). For a PSA < 10 ng/ml, main grade 3 was associated with a
      better laboratory progression-free survival rate than main grade 4 (p = 0.0007).
      No difference in terms of laboratory progression was observed in the presence of
      extraprostatic extension or PSA > 10 ng/ml. CONCLUSION: A high correlation was
      observed between the main grade of Gleason score 7 and laboratory progression
      free survival. Main grade 3 constituted a factor of better prognosis than main
      grade 4.

PMID- 11980013
TI  - [Value of mitoxantrone in metastatic hormone-resistant prostate cancer].
AB  - INTRODUCTION: The second-line treatment of hormone-resistant metastatic prostate
      cancer is controversial. This study was designed to evaluate the efficacy and
      toxicity of mitoxantrone in this clinical situation. MATERIALS AND METHODS: The
      author report a retrospective study of 16 patients with a mean age of 69 years
      (range: 51-80 years). In each case, the treatment regimen consisted of castration
      followed by fosfestrol tetrasodium after hormonal escape and second-line
      treatment with mitoxantrone at a dose of 12 mg/m2 per course (1 to 10 courses)
      associated with prednisone at a dose of 10 mg/day. The authors evaluated the
      response to treatment (clinical status and survival) as a function of the
      following parameters: initial PSA, Gleason score, number of bone metastases, time
      to hormonal escape, PSA and Karnofsky index on inclusion and total number of
      courses of mitoxantrone. RESULT: Two groups of eight patients were defined as a
      function of clinical status at the end of each course: group 1 (partial
      regression and no change) and group 2 (tumour progression). A correlation was
      demonstrated between the time to hormonal escape and the number of courses and
      the response to treatment (p = 0.058). The mean survival after introduction of
      mitoxantrone was 13 months with a significant difference (p = 0.0004) for a cut
      off value of 4 courses: 7 months (n < or = 4) and 18 months (n > 4). CONCLUSION:
      Mitoxantrone is a minimally toxic chemotherapeutic agent, which justifies its
      current indication in hormone-resistant advanced prostate cancer.

PMID- 11980014
TI  - [Systematic planning of technical training in urologic surgery: methodologic
      trial].
AB  - OBJECTIVES: Trainee urologists must be helped and guided in order to acquire
      surgical techniques and professional skills. This methodological trial was
      designed to define the training objectives based on the needs formulated in terms
      of basic technical procedures. MATERIALS AND METHODS: Systematic planning based
      on the training cycle was used in this study. Training needs were identified by a
      questionnaire sent to 4 groups composed of a limited number (about twelve) of
      urologists, but representative of the various modes of urological practice in
      several regions of France. Data were acquired according to the Delphi method.
      RESULTS: A list of 10 operations to be mastered at the end of urology training
      was defined consensually based on the replies (79.2%) to the questionnaire. This
      list was used as the basis for the design of general and specific training
      objectives for each operation. These objectives were validated by the urologists
      consulted. Three examples of these objectives are presented. CONCLUSION: A clear
      determination of the surgical technique training needs and objectives could lead
      to standardization of the practical training of urology residents. This would
      subsequently need to be completed by determination of the methods of evaluation
      of achievement of these objectives for tutors and trainee urologists.

PMID- 11980015
TI  - [Prevalence and risk factors of urinary incontinence in young women].
AB  - OBJECTIVE: Urinary incontinence is a very common disease among women but only few
      studies have been published in young adult and middle-aged population. We studied
      urinary incontinence prevalence and risk factors in this young and middle-aged
      population. MATERIAL AND METHODS: We studied during the year 1998 the prevalence
      of global incontinence and stress, urge and mixed urinary incontinence in 1700
      women working in a French academic hospital (n = 2800). Women received the
      questionnaire at the same time than their convocation for their yearly visit in
      occupational medicine. Usual risk factors of constitutional events (increasing
      age, obesity defined by a Body Mass Index > or = 25); obstetric events
      (pregnancy, previous caesarean delivery, previous vaginal delivery, post-partum
      incontinence) and gynaecological event (hysterectomy) were evaluated. RESULTS:
      177 women (mean age 40.0 years) returned the questionnaire. 467 women (27.5% 95%
      CI = 25.4-29.7) reported urinary incontinence, 210 (12.4% 95% CI = 10.8-14.0)
      stress urinary incontinence, 28 (1.6% 95% CI = 1.1-2.4) urge urinary incontinence
      and 229 (13.5% 995% CI = 11.9-15.2) mixed urinary incontinence. 38 women (8.1%)
      suffered from frequent urinary leakage corresponding to 1 (0.5%), 4 (14.3%) and
      33 (14.4%) stress, urge and mixed urinary incontinence. The prevalence of urinary
      incontinence increased significantly with age > or = 40 years (RR = 2.16 95% CI =
      1.86-2.57) pregnancy (RR = 2.22 95% CI = 1.71-2.87), previous vaginal delivery
      (RR = 2.15 95% CI = 1.72-2.69), post-partum incontinence (RR = 2.57 95% CI = 2.22
      2.97, hysterectomy (RR = 1.52 95% CI = 1.11-2.08). Obesity (RR = 1.14 95% CI =
      0.99-1.32) and previous caesarean delivery (RR = 2.15 95% CI = 1.72-2.69) did not
      increase the risk of urinary incontinence. The risk factors for stress urinary
      incontinence were age > or = 40 years (RR = 2.18 95% CI = 1.66-2.87), pregnancy
      (RR = 2.36 95% CI = 1.55-3.58), previous vaginal delivery (RR = 2.47 95% CI =
      1.70-3.59), post-partum incontinence (RR = 2.78 95% CI = 2.14-3.61) and
      hysterectomy (RR = 2.83 95% CI = 1.93-4.15). No relationship was found between
      stress urinary incontinence and obesity (RR = 1.25 95% CI = 0.96-1.64) and
      previous caesarean delivery (RR = 1.02 95% CI = 0.45-2.32). CONCLUSION: A high
      prevalence of urinary incontinence was observed among young adult and middle-aged
      female hospital workers with an easy access to medical resources. Gynaecological
      and obstetric event (pregnancy particularly previous vaginal delivery and
      hysterectomy) were the most prominent risk factors, especially for stress urinary
      incontinence.

PMID- 11980016
TI  - [Surgical cure of stress urinary incontinence with vaginal tissue sling:
      technique, results, indications].
AB  - OBJECTIVES: Describe a new surgical technique of sling procedure using a vaginal
      sling and report complications and mid-term functional results. According to
      these results, it's necessary to discuss the best indications. MATERIAL AND
      METHODS: Retrospective study of the first 75 patients operated for urinary stress
      incontinence. RESULTS: The average age of patients was 56 (30-90). Preoperative
      complications have been rare with only one bladder injury (1.3%). Postoperative
      complications have been more frequent and the most of them was caused by 76% of
      urine retention lasting a mean of 14 days and 44% of urinary infections. 20% of
      the patients have presented secondary dysuria and/or urinary urgency. 4 patients
      (5.3%) have presented a vaginal mucocele between 9 and 32 months after the
      operation. At mean follow-up of 25.1 months, the success rate was 70.6%, with
      61.3% of patients who have been cured and 9.3% which was improved. In case of
      severe sphincter insufficiency, the success rate was 80%. Success rate was 30%
      when the vaginal sling was the only procedure and 66.1% when it was associated to
      another vaginal procedure (p = 0.006) as vaginal hysterectomy or sacro-spinous
      suspension. CONCLUSION: This original surgical technique for cure of urinary
      stress incontinence is inexpensive and easy to learn. It can be associated to
      other operations by vaginal way. The realization of this procedure under regional
      anaesthesia should enable to warn urine retention which is the mean postoperative
      complication. The success rate of this series is cheerful because it takes into
      account any patients no selected and operated on the learning phase of the
      technique. The best results of this technique are urinary stress incontinence
      associated with vaginal surgery for genital prolapse. The final assessment of
      this surgical technique will be require longer follow-up and comparative studies
      with other procedures on an elevated number of patients.

PMID- 11980017
TI  - [Treatment of stress urinary incontinence with tension-free vaginal tape (TVT).
      Mid-term results of a prospective study of 124 cases].
AB  - OBJECTIVES: The role of urethral support in continence has been stressed since
      1994, resulting in a new technique for repair of stress urinary incontinence:
      Tension-free Vaginal Tape (TVT). This technique has been performed in France
      since 1996 and we analyse the results of this technique in 124 consecutive
      patients treated for stress urinary incontinence. MATERIAL AND METHOD: The 124
      patients did not present any prolapse requiring surgical repair and presented
      clinical urine leaks on effort after filling the bladder with 250 ml of
      physiological saline (stress test). 29 patients had already been operated for a
      disorder of pelvic tone, combined with an urological procedure in 22 cases; all
      patients completed an urodynamic assessment. 54 patients presented clinical signs
      of urgency in addition to stress urinary incontinence and 6 of them had
      cystomanometric signs of urgency. The mean maximum urethral closure pressure was
      47 cm H2O (range: 12-120). All patients were operated under local anaesthesia
      (0.25% Xylocaine with adrenaline) according to the same standardized protocol.
      The mean follow-up was 35.2 months (range: 19-54). The operative and
      postoperative morbidity, the results demonstrated by stress test, the subjective
      result assessed by a patient satisfaction questionnaire and long-term
      complications were analysed. RESULTS: 110 patients (98.7%) were totally
      continent, 10 (8%) were improved and 4 (3.3%) were failures. 117 patients (94.3%)
      were satisfied. Signs of urgency resolved in 38 out of 54 patients (63%). The
      result was not influenced by closure pressure. Complications consisted of 11
      bladder perforations (8.9%) and 3 haematomas, none of which required reoperation.
      Micturition was easily resumed in 122 patients, while acute retention was
      observed in 2 cases, on D2 and D3. In 76 patients (61.3%), the first residual
      urine was less than 100 ml. Long-term follow-up did not reveal any cases of
      rejection of the TVT, but 3 vaginal erosions were treated by simple plasty.
      CONCLUSION: With a follow-up of three years and an experience of 5 years, this
      series demonstrates the value of the TVT technique for treatment of female stress
      urinary incontinence based on the good results (objective: 89%; subjective: 95%),
      reproducibility, simplicity and low morbidity.

PMID- 11980018
TI  - [Urethral sagittal duplication in children. Report of 7 cases].
AB  - Urethral duplication is a rare disease with various clinical expressions and
      treatments. The authors report 7 cases. MATERIAL AND METHODS: The authors
      retrospectively review 7 children with sagittal duplication of the urethra seen
      between 1995 and 2000. All children were investigated by ultrasonography of the
      urinary tract, retrograde cystography and voiding cystourethrography. RESULT:
      Except for one case of neonatal discovery, the mean age at diagnosis in the other
      six children was 4 years. In one case, the malformation consisted of blind
      incomplete urethral duplication (type I B) and urethroscopy confirmed the
      presence of an orifice distal to the urethral cap; symptomatic treatment was
      successful in this patient. Two children with complete urethral duplication with
      epispadias and two bladder orifices (type II A1) were successfully treated by
      resection of the supernumerary urethra. One child presented an U-shaped
      duplication (type II A2 "Y"). Unsuccessful opacification of the accessory urethra
      prior to its resection induced sclerosis and no flow with a follow-up of 24
      months. Penile surgery was performed in two children with incomplete urethral
      duplication with only one vesical orifice (type II A2) transforming duplex
      urethra into distal bifid urethra after resection of the accessory urethra and
      its epispadic meatus. One child had a suspended duplication of the urethra with
      only one glandular meatus (type II B2) and a single vesical orifice. He was
      treated by endoscopic section of the urethral membrane separating the two
      urethras before their fusion in the bulbar urethra. With a mean follow-up of 36
      months (range: 6 months to 4 years) no infectious or voiding complications were
      observed in these 7 children. CONCLUSION: Sagittal duplication of the urethra is
      a rare disease requiring precise anatomical and functional assessment. The ideal
      treatment for symptomatic forms is resection of the duplication without impairing
      sphincter function.

PMID- 11980019
TI  - [Biopsies of the transitional zone: impact on the detection of prostatic cancer
      and prognostic value].
AB  - OBJECTIVE: To analyse the value of biopsies of the transitional zone (TZ) in the
      detection of prostate cancer and their prognostic value. METHODS: The authors
      reviewed the literature on directed biopsies of the TZ and discuss the most
      recent publications concerning the impact of these biopsies on prostatic cancer
      detection and the prognosis of cancers of the TZ. RESULTS: There are currently
      few arguments in favour of biopsies of the TZ during a first series of prostatic
      biopsies, as the incidence of cancers situated exclusively in the TZ is low and
      first-line biopsies of the TZ do not significantly increase the cancer detection
      rate. However, when a suspicion of cancer persists after a first series of
      negative biopsies, or in patients with a large prostate, biopsies of the TZ can
      be indicated, as some authors consider that they considerably increase the cancer
      detection rate. Some authors have suggested that cancers of the TZ have a better
      prognosis than peripheral cancers because of their more favourable histological
      characteristics. These results need to be confirmed on larger scale studies.
      CONCLUSIONS: There are two situations in which biopsies of the TZ have a
      potential value: (1) as a second-line investigation in the case of persistent
      suspicion of prostate cancer after a first series of negative peripheral
      biopsies; (2) in patients with a very large prostate. The prognosis of cancers
      situated exclusively in the TZ is still poorly known, and the management of this
      type of cancer must remain the same as that of peripheral cancer.

PMID- 11980020
TI  - [Renal oncocytoma: report of 5 cases].
AB  - Renal oncocytoma is a rare, benign tumour, which is rarely diagnosed
      preoperatively. The authors report 5 cases of renal oncocytoma operated over a 10
      year period. Based on a review of the literature, the various complementary
      investigations allowing a preoperative diagnosis and the indications for
      conservative surgery are discussed and analysed.

PMID- 11980021
TI  - [Renal tuberculosis and renal adenocarcinoma: a misleading association].
AB  - The association of renal cancer and renal tuberculosis is uncommon. While the
      incidental discovery of renal cell carcinoma in a tuberculous kidney is a
      classical finding, the discovery of tuberculous lesions after nephrectomy for
      cancer is exceptional. The authors describe the case of a patient operated for
      renal cancer in whom histological examination revealed associated renal
      tuberculosis.

PMID- 11980022
TI  - [Report of a case of leiomyoma of the kidney].
AB  - The authors report a case of leiomyoma of the renal capsule. Although leiomyoma
      is a frequent tumour in the uterus, leiomyomas of the urinary tract are very
      rarely reported in the literature. This tumour has an excellent prognosis. In
      rare cases, the diagnosis may be suggested by CT scan, but histological
      examination confirms the diagnosis of benign tumour.

PMID- 11980023
TI  - [Urachal adenocarcinoma: analysis of 3 cases].
AB  - Adenocarcinoma of the urachus is a very rare disease. It often remains
      undiagnosed for a long time and has an aggressive course. Surgery, the only
      potentially curative treatment, was initially very extensive, but this attitude
      has been revised more recently. The authors present three clinical cases, and
      discuss the treatment options. The first two cases were treated by one-stage
      resection and the third case, which presented with a mucus collection in the
      abdomen with "signet ring" cells, was treated by Intraperitoneal
      ChemoHyperthermia (IPCH) during second-look laparotomy. A review of the
      literature shows that the current tendency is towards less mutilating surgery.
      Diagnostic examinations, allowing earlier detection of this disease, may possibly
      alter its prognosis, which was considered to be very poor up until recently.

PMID- 11980024
TI  - [Chemotherapy: principles and practice].

PMID- 11980025
TI  - [Role of mitoxantrone in the treatment of hormone-independent metastatic cancer
      of the prostate].

PMID- 11980026
TI  - [CAT Scan in hormone-independent prostate cancer].

PMID- 11980027
TI  - [Hormone independent prostatic cancer].

PMID- 11980028
TI  - Psychic and social reality in aging.

PMID- 11980029
TI  - Phallic narcissism, anal sadism, and oral discord: the case of Yukio Mishima,
      Part I.
AB  - Thus far I have explored Mishima's traumatic childhood and the experiences
      leading him toward misogyny, phallic narcissism, and the drive to murder his own
      weakness and sexual vulnerability. Mishima suffered the extraordinary trauma of
      being separated from his parents and sequestered to the sickroom of a psychotic
      grandmother for the first twelve years of his life. Intense rage over abandonment
      and impingement engendered a disgust for femininity and the need to escape
      feminine messiness through homosexual pursuits. Mishima's entrenched feelings of
      shame and weakness gave rise to phallic narcissistic tendencies, as he idealized
      powerful men and eventually strove to become a powerful and beautiful male. In
      pursuing this erotic masculine image Mishima continued to fantasize about
      murdering his weak and shameful self-image, and commingled this sadistic impulse
      with fantasies of sexual merger with murdered love objects. Finally Mishima was
      the murderer erotically eradicating his sexual vulnerability as both subject and
      object. His suicide was a repetition of this erotic sadistic fantasy. In a
      further article I will continue the discussion by examining Mishima's fantasies
      of murdering beautiful and abandoning love objects. I will also address the
      complex nature of his ritual suicide as fantasy of rebirth, sexual merger, the
      murder of toxic introjects, and escape from death, decay, and regression to
      helpless infancy.

PMID- 11980030
TI  - Hans Loewald: the psychoanalyst as mystic.

PMID- 11980031
TI  - On "Unitive distortions": toward a differential assessment of religious ecstasy.

PMID- 11980032
TI  - The unconscious as symbolopoiesis.

PMID- 11980033
TI  - Family economic resources in the post-reform era.
AB  - Aided by the longest economic expansion in U.S. history and other policy changes
      designed to make work pay, federal welfare reform legislation has spurred mothers
      to leave welfare at an unprecedented rate. The majority of mothers who left
      welfare are working, but most have jobs with low pay and limited benefits. This
      article discusses the relationship between economic resources and child well
      being, and how family economic resources have changed under welfare reform. A
      survey of the research conducted since reform indicates the following: Families'
      economic resources clearly matter to child well-being, but the connections are
      complex and vary by the age of the child. Without the benefit of supports
      designed to "make work pay," many families working full time at the minimum wage
      have resources beneath the poverty line, and the poverty line itself falls
      substantially short of the needs of most working families. Although poverty
      overall has declined under welfare reform, a significant segment of families are
      worse off--in part because after leaving welfare, many families do not receive
      other government supports designed to help them. Most states are still struggling
      to design more effective systems for delivering supports to help low-income
      working families move out of poverty. The author cautions that the evolving story
      of welfare reform will need to be monitored carefully to achieve long-term
      positive impacts on family economic resources and child well-being.

PMID- 11980034
TI  - Welfare reform, fertility, and father involvement.
AB  - Recognizing that most poor families are single-parent families, the federal
      welfare reform law of 1996 emphasized the responsibility of both parents to
      support their children. In addition to strengthening the child support
      enforcement system, the law included several provisions designed to decrease
      childbearing outside of marriage and to promote two-parent families. This article
      focuses on the important role that fathers play in children's lives and how
      public policies have affected childbearing and father involvement. Key
      observations are: Compared with children living with both biological parents,
      children in father-absent families often have fewer economic and socioemotional
      resources from their parents, and do not fare as well on many outcome measures.
      Efforts to reduce the rising number of father-absent families by focusing on
      preventing unwanted pregnancy among unmarried women, especially teen girls, have
      met with some success; those programs seeking to alter adolescents' life
      opportunities in addition to providing education or family planning services
      appear to hold the most promise. Efforts to encourage greater father involvement
      by focusing almost exclusively on increasing absent parents' child support
      payments reap only minimal benefits for poor children because their absent
      parents often have few resources and little incentive to make support payments.
      To date, efforts to increase the emotional involvement of unmarried fathers with
      their children have produced disappointing results, but new research suggests
      that such programs can make a difference when targeting fathers at the time of a
      child's birth. Many children spend some time living away from their fathers,
      deprived of the financial and emotional resources they can provide. Because of
      the importance of fathers to child well-being, the authors conclude that new
      directions in research and public policies are needed to encourage greater father
      involvement across the wide diversity of family arrangements in society today.

PMID- 11980035
TI  - Welfare reform and parenting: reasonable expectations.
AB  - Although the primary goals of federal welfare reform legislation were to move
      welfare mothers into the workforce and reduce births outside of marriage,
      promotion of responsible parenting was also an important underlying theme.
      Parenting is a complex, multifaceted phenomenon, however, encompassing a wide
      range of functions related to nurturing, discipline, stimulation, values,
      activities, and routines. This article provides a framework for assessing the
      impact of welfare reform on various dimensions of parenting, with the following
      key findings: Many aspects of life affect parenting and child development, such
      as parent characteristics, child characteristics, family economic resources,
      family structure, parental mental health, marital or partner relationships, and
      the quality of parents' kin and social networks. About two-thirds of states are
      using federal welfare funds to promote better parenting through programs such as
      home visits to new parents and parenting classes, but virtually no state
      parenting programs have been evaluated. Welfare reform appears to have limited
      effects on parenting. The only dimension of parenting significantly affected by
      some welfare demonstration programs was parents' choice of child care settings
      and extracurricular activities for their children. The programs with the greatest
      positive impact on parenting were those with more generous work supports and more
      flexible work requirements. Not only did these programs lead to different choices
      concerning child care and activities for preschool and school-age children, but
      they also resulted in more stable marriages and less violence between partners,
      which also could lead to improved parenting. The authors conclude that many
      important aspects of the connection between welfare reform and parenting have yet
      to be examined, and that further research is needed to identify the ways states'
      welfare programs can promote better parenting.

PMID- 11980036
TI  - Looking to the future.

PMID- 11980037
TI  - The 1996 welfare law: key elements and reauthorization issues affecting children.
AB  - The Personal Responsibility and Work Opportunity Reconciliation Act of 1996
      changed the social policy landscape for children in many ways. It replaced the
      prior welfare program with block grants to the states entitled Temporary
      Assistance for Needy Families, and modified a broad array of other programs and
      initiatives affecting low-income children. This article describes the key themes
      dominating the debate over welfare reform in 1996, specifically: Increased state
      discretion in program design, leading to more variability in states' eligibility
      requirements and services provided to low-income families; More stringent work
      requirements even for parents of very young children; Time limits on the use of
      federal funds for cash assistance, and a strong focus on caseload reduction;
      Increased emphasis on parental responsibility, with stronger child support
      requirements; and Increased emphasis on reducing out-of-wedlock births, including
      bonuses to states with the largest reductions, and special requirements for
      unmarried teen parents who seek welfare. Although child well-being received
      little attention during the congressional debates in 1996, the authors conclude
      with the hope that improving child outcomes and child well-being will emerge as a
      key theme when the law is reauthorized in 2002.

PMID- 11980038
TI  - Children and welfare reform: analysis and recommendations.

PMID- 11980039
TI  - Reforms and child development.
AB  - Since their inception in the 1930s, U.S. welfare and income support programs have
      played an important role in providing benefits to children. Unlike programs
      directly targeted to children, however, welfare programs are designed to produce
      economic and employment impacts on adults, so that any effects on children would
      be indirect. This article explores the influence of such programs on children's
      well-being and development, first by defining goals for children's healthy
      development, then by proposing a framework for understanding the impact of
      welfare policies on children. A review of the literature within each component of
      this framework reveals the following: Measures of children's well-being should
      encompass physical, intellectual, social, and emotional development. The physical
      and material environment, family environment, and social and community
      environment can all affect a child's healthy development. Policies designed to
      increase maternal employment, reduce welfare use, and strengthen families do not
      necessarily lead to more positive environmental contexts and increased child well
      being. The author concludes that to ensure positive impacts on children, welfare
      and income support policies must move beyond their exclusive emphasis on adults
      and include goals that focus on improving children's social and physical
      environments at home and in the community.

PMID- 11980040
TI  - Experimental studies of welfare reform and children.
AB  - Even prior to passage of federal welfare reform, many demonstration programs
      anticipated key features of the 1996 law, such as "work-first" strategies, time
      limits on welfare receipt, and financial incentives to work. Over the past
      decade, 10 experimental evaluations of these programs have extended their studies
      to examine the impacts on children. This article provides a synthesis of findings
      from the first seven of these studies to release results concerning child
      impacts. Key observations include the following: Across the different types of
      welfare-to-work programs examined, researchers found neither widespread harm nor
      widespread benefit to young children, but some significant impacts did occur.
      Favorable impacts tended to occur in programs that improved family economic
      status or maternal education, but these programs still did not bring children to
      the level of national norms for positive child development. Unfavorable impacts
      tended to occur when families did not show economic progress or when their
      economic situation worsened, when the children were adolescents, and-
      unexpectedly--when the families were believed to be at lower risk for long-term
      welfare receipt. Thus, although impacts were not widespread, these programs did
      have the potential to affect children for both better and worse across a range of
      developmental outcomes. The authors conclude that these findings underscore the
      importance of strengthening program approaches to enhance developmental outcomes
      for children in families being served by the welfare system.

PMID- 11980041
TI  - Welfare reform and child care options for low-income families.
AB  - For the changes under welfare reform to positively affect children, the gains
      that mothers make from employment must lead to improvements in children's daily
      settings at home, in child care, at school, or in the community. This article
      focuses on the role child care can play in promoting the development of, and life
      opportunities for, low-income children. Key observations include: Total federal
      and state funding for child care for welfare and working poor families has
      increased dramatically since welfare reform, from $2.8 billion in 1995 to $8.0
      billion in 2000. The majority of welfare mothers tend to rely on informal child
      care arrangements when first participating in welfare-to-work programs, but as
      they move off welfare and into more stable jobs, they are more likely to choose a
      center or a family child care home. Although children from poor households stand
      to benefit the most from high-quality care, they are less likely to be enrolled
      in high-quality programs than are children from affluent families, partly due to
      uneven access to high-quality options in their neighborhoods. Less than one
      quarter of all eligible families use child care subsidies, and usage varies
      widely across states and local areas reflecting various barriers to access and
      scarcity of quality center-based care. The authors conclude that to achieve
      welfare reform's ultimate goal of breaking the cycle of intergenerational poverty
      and dependence on government benefits, welfare-to-work programs should promote
      learning and development among children in welfare and working poor families by
      increasing access to high-quality child care in low-income neighborhoods.

PMID- 11980042
TI  - Children and welfare reform. Selected bibliography.

PMID- 11980043
TI  - A personal response to Gail Hornstein's To redeem one person is to redeem the
      world: the life of Frieda Fromm-Reichmann.
AB  - This article summarizes events surrounding the closing of Chestnut Lodge, as a
      backdrop to the author's reactions on reading Frieda Fromm-Reichmann's biography.
      This anecdotal piece forms a complementary essay with the 2000 Frieda Fromm
      Reichmann Lecture, "The Current Relevance of Fromm-Reichmann's Works." It
      illustrates aspects of treatment of schizophrenia and of the individuals involved
      in such work.

PMID- 11980044
TI  - Memory, neurodynamics, and human relationships.
AB  - In this article we discuss the implications of the functional organization and
      dynamics of the brain for understanding human relationships. In particular, we
      focus on the brain's multiple memory systems and the various roles they play in
      organizing the interactions of people as they come to know one another. The
      distinction between the relatively independent declarative, procedural, and
      emotional learning systems is especially significant in this regard, as the
      former mediates what we know about one another, the second mediates what we do
      with one another, and the third affects behavior by altering our emotional state.
      Knowledge of the functioning of these dissociable memory systems provides a novel
      perspective on relationships--both ordinary social relationships and those that
      develop in psychotherapy--and further illuminates psychotherapeutic transference
      and countertransference phenomena. We begin with a review of the neural basis of
      these processes, then turn our attention to the interpersonal level of analysis.

PMID- 11980045
TI  - Right frontal EEG and pregnancy/neonatal outcomes.
AB  - Fifty-two pregnant women recruited during their second trimester were given EEGs
      and divided into greater relative right and left frontal EEG activation groups.
      The greater relative right frontal EEG women had lower dopamine levels during
      their second trimester and lower dopamine and higher cortisol levels during the
      neonatal period. The newborns of the right frontal EEG mothers also showed
      greater relative right frontal EEG, had lower dopamine and serotonin levels,
      spent more time in indeterminate sleep and had inferior Brazelton scores. A
      discriminant function analysis based on the mothers' prenatal depression scores
      and biochemical measures correctly classified 74% of the women as greater
      relative right or left frontal EEG group members.

PMID- 11980046
TI  - Toward an integration of interpersonal and biological processes: evolutionary
      psychiatry as an empirically testable framework for psychiatric research.
AB  - Phenomenological, biological, and interpersonal aspects of psychiatric disorders
      lack an integrative empirical framework. In this paper evolutionary psychiatry is
      proposed as a meta-theory to integrate biological and interpersonal aspects of
      psychopathology. Pathological cognition, emotions, and behaviors may be examined
      according to specific biosocial goals originally pursued to increase the
      individual's inclusive fitness, similar to the ways that "normal" processes have
      been analyzed by evolutionary psychology. Sex-specific differences in prevalence
      rates and symptomatology of psychiatric disorders may also be better understood
      if divergent problems of adaptation for men and women in human evolutionary
      history are taken into account. Instead of mistaking the evolutionary approach
      for being deterministic and empirically untestable, it may rather be appropriate
      to provide a functional classification which adds to the contemporary psychiatric
      nosology through analysis according to specific conflicts of adaptation (at the
      ultimate level), the pursuit of biosocial goals, and proximate specifiers such as
      genetic, developmental, and interpersonal causes of disorders.

PMID- 11980047
TI  - Electronic chips implant: a new culture-bound syndrome?

PMID- 11980048
TI  - [The establishing of a state sanitary-epidemiological supervision in occupational
      health: its goals and prospects].
AB  - The requirements are: improved legal basis for work safety and health care of
      workers; establishment of state sanitary and epidemiologic supervision, system
      for disclosure and account of occupational diseases in the country and regions;
      higher role of Research Centers and colleges in specifying scientific and medical
      documents to help practical medicine. The authors present parameters of
      occupational morbidity over 10 years (1991-2000) and stress that work conditions
      and workers' health state did not improve during the period, demonstrate high
      occurrence of accidents. The authors necessitate more attention to small business
      enterprises, sketch achievements of Research Centers with RAMSc and Health
      Ministry in specifying methods and principles to evaluate health risk under
      exposure to environmental and occupational factors, to set hygienic regulations
      (including those for complex exposure). The authors formulated main directions of
      State Sanitary and Epidemiologic Supervision activities: improvement of sanitary
      laws, scientific basis for sanitary and epidemiologic supervision, skill
      formation, management measures).

PMID- 11980049
TI  - [Strategies in approaches to requirements in the control of electromagnetic
      irradiation levels].
AB  - The authors present main principles and approaches used in elaboration of
      methodic documents to control electromagnetic levels in enterprises that work in
      radio frequency range. The article incorporates list of actual methodic documents
      specified in accordance with those principles and approaches.

PMID- 11980050
TI  - [Occupational health evaluation of electromagnetic fields in electric trains and
      subway technologic areas].
AB  - The article represents measurements and hygienic evaluation of electromagnetic
      fields in rolling stock and various technologic areas of subway. Results prove
      that specification of MALs for electric transport magnetic fields is essential
      for workers and general population. Before the MALs specification, the authors
      suggest that temporary allowable levels should be set according to national and
      foreign research.

PMID- 11980051
TI  - [On remodeling of heart in vibration disease].
AB  - Vibration disease induces disorder of cardiac functional state in accordance with
      the disease severity. Cardiac dysfunctions are changed geometry and weight of
      left ventricle, disordered diastole of both ventricles, altered left atrium
      activity, increased pressure in pulmonary artery, higher postload on right
      ventricle.

PMID- 11980052
TI  - [B-mode ultrasonography scanning main arteries of upper limbs in vibration
      disease patients].
AB  - The objective was to use B-mode ultrasonography for assessing vascular walls of
      upper limbs main arteries in vibration disease patients. Imaging of the arterial
      walls revealed changes concerning increased intima-media complex (IMC). Ratio of
      IMC to vascular diameter was considerably higher in vibration disease patients-
      0.233 +/- 0.013 vs control value of 0.156 +/- 0.014 (p < 0.01). Vibration could
      result in destruction of some endothelial cells and significant release of
      endothelial growth factors.

PMID- 11980053
TI  - [Health risk factors for health personnel].
AB  - The authors present data on air pollution in medical establishments of Riga. The
      average concentrations of chemicals do not exceed the MACs in hospital
      compartments. Short-term concentrations of some chemicals in operating rooms and
      laboratories are considerably higher than the corresponding normal values.
      Doctors' offices appeared to have increased bacterial contamination. The
      calculated exposure for chemical mixture was recommended for risk evaluation.

PMID- 11980054
TI  - [Objective and subjective data on occupational morbidity among medical personnel
      of Latvia].
AB  - Significant evidence prove that actual occupational morbidity among medical
      staffers is considerably higher than official values. Disclosed lower and medium
      performance index results from contact with occupational hazards.

PMID- 11980055
TI  - [Occupational health among those engaged in physical activities and sports].

PMID- 11980056
TI  - [Ways to improve teaching of occupational diseases for under- and post-graduate
      students].

PMID- 11980057
TI  - [The status of cardiovascular system in electric networks dispatchers].
AB  - Ageing results in increased role of vessels and lower role of myocardium in self
      regulation of circulation; longer length of shift work leads to higher systolic,
      pulse and average dynamic BP: longer length of dispatching work causes higher
      ratio of systolic BP to pulse rate. Shift work increases occurrence of
      unfavorable cardiovascular changes by 4-12 years; peculiarities of the
      dispatcher's work speed this course by extra 2 years. The earliest unfavorable
      changes with the process are seen in vascular portion.

PMID- 11980058
TI  - The inherited epilepsies.
AB  - Our knowledge regarding the genetic bases of the human epilepsies is in a state
      of rapid flux. For some forms of epilepsy, epidemiologists are still trying to
      determine whether there is any familial (hereditary) predisposition. Other forms
      of epilepsy are known to run in families, but the mode of inheritance and degree
      of penetrance of the trait are still in doubt. Three forms of epilepsy have been
      tentatively localized to specific chromosomes, and several others are being
      analyzed with linkage analyses. In no case, has the gene responsible for any
      human epilepsy been isolated or characterized and we are not yet close to
      understanding how any specific genetically controlled biochemical or
      physiological parameter is responsible for the development of an epilepsy
      syndrome or of any specific epileptogenic increase in brain excitability.
      However, an extensive animal literature indicates that the mechanisms will be
      complex as a common phenotype can be the expression of multiple genes, and a
      single gene can be associated with several phenotypes (Buchhalter, 1993).

PMID- 11980059
TI  - Neurological diseases due to mitochondrial DNA mutations: concepts and problems
      in pathogenesis.

PMID- 11980060
TI  - The molecular genetics of neurological disease.

PMID- 11980061
TI  - The neurobiology of narcolepsy-cataplexy syndrome.
AB  - The pathophysiology of narcolepsy is closely related to the abnormalities of REM
      sleep that are the electrophysiologic signature of the syndrome. Evidence from
      studies of canine narcolepsy and postmortem human narcoleptic brain tissue
      provide strong evidence that cholinergic and monoaminergic systems involved in
      REM sleep regulation are abnormal in narcolepsy but the primary neurochemical
      abnormality has not yet been determined. There is now conclusive evidence that a
      genetic basis is required for all or almost all cases of narcolepsy. In the vast
      majority of narcoleptics, a gene closely linked to the HLA-DR/DQ region appears
      to confer narcoleptic susceptibility, but the penetrance of the gene is low and
      additional environmental and perhaps genetic factors are required to express the
      disease. In a minority of narcoleptics, there may be a second autosomal dominant
      gene not linked to HLA-DR2 that facilitates the occurrence of narcolepsy. This
      gene may be related to the mu-immunoglobulin heavy-chain switch-like segment that
      has been implicated in canine narcolepsy. There appear to be at least two
      narcoleptic phenotypes associated with the narcoleptic susceptibility gene or
      genes: narcolepsy-cataplexy syndrome and monosymptomatic narcolepsy, or
      narcolepsy with REM sleep abnormalities but without cataplexy. Idiopathic
      hypersomnia without cataplexy or REM sleep abnormalities may represent a third
      phenotype, although most cases of idiopathic hypersomnia are probably unrelated
      to the HLA-D linked gene. The link between the genetic basis of narcolepsy and
      its neurochemical abnormalities is still entirely unknown. Although the
      hypothesis that a transient immune-mediated reaction leads to a permanent
      alteration of monoaminergic function is appealling, there is no direct evidence
      to support this hypothesis. Several important questions concerning the
      neurobiology of narcolepsy remain to be answered. What is the specific gene in
      the HLA-D region that is linked to human narcolepsy and what are the products or
      functions of the gene that predispose to narcolepsy? Does the human mu-switch
      region contain genetic material homologous to the 85-kb band linked to canarc-1
      that predisposes to narcolepsy? What are the environmental factors required for
      expression of the disease in susceptible individuals and do they incite
      immunologic processes? Which of the neurochemical abnormalities are primary,
      which are secondary or compensatory, and how do they relate to the predisposing
      genetic and environmental elements? Additional familial, genetic, and
      neurochemical studies over the next decade should lead to more complete
      understanding of the neurobiology of narcolepsy and ultimately to better
      treatments for this chronic disabling disease.

PMID- 11980062
TI  - Genetics of Alzheimer's disease.
AB  - Alzheimer's disease is the leading cause of dementia in the elderly. Most
      patients do not have an obvious family history and are classified as sporadic.
      Genetic factors in early and late-onset Alzheimer's disease are now well
      documented. This paper reviews the known genetic loci associated with Alzheimer's
      disease with an emphasis on the role of apolipoprotein E in late-onset familial
      and sporadic disease. Apolipoprotein E allele 4 is a susceptibility gene that is
      found in approximately 50% of patients with Alzheimer's disease. Hypotheses about
      apolipoprotein E function that may lead to Alzheimer's disease are also
      discussed.

PMID- 11980063
TI  - Molecular genetic analysis of neuronal ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses comprise a group of inherited
      neurodegenerative disorders characterized by the accumulation of autoflourescent
      lipopigment in neurones and other cell types. Three main childhood sub-types
      occur: infantile (Haltia-Santavouri disease, locus CLN1), late-infantile (Jansky
      Bielschowsky disease, locus CLN2) and juvenile (Spielmeyer-Sjogren-Vogt, Batten
      disease, locus CLN3). Inheritance is autosomal recessive. The basic biochemical
      defect remains unknown. The infantile disease Iocus (CLN1) has been mapped to
      human chromosome 1p32 and the juvenile disease Iocus (CLN3) to human chromosome
      16p12 by linkage analysis. Marker loci in strong allelic association with the
      disease loci have been identified in each case and haplotype analysis suggests a
      founder mutation for CLN1 and CLN3. Classical late-infantile disease (CLN2) has
      been shown not to be an allelic variant of either CLN1 or CLN3. Identification of
      linked markers has provided a new method for pre-natal diagnosis. Work is in
      progress to clone CLN1 and CLN3 and to map CLN2. This will allow elucidation of
      the molecular genetic basis of the neuronal ceroid lipofuscinoses.

PMID- 11980064
TI  - A molecular genetic approach to amyotrophic lateral sclerosis.
AB  - Disorders of the motor neurons may affect both the upper and lower neurons,
      primarily the lower motor neurons as in the spinal muscular atrophies are
      primarily the upper motor neurons as in the familial spastic paraplegias.
      Amyotrophic lateral sclerosis is a degenerative disorder of the motor neuron that
      results in paralysis and wasting of voluntary muscles. Large motor neurons in the
      cerebral cortex, brain stem and spinal cord degenerate or are lost. Hyaline
      inclusions may be seen in the cytoplasm of surviving motor neurons. Acute axonal
      degeneration of peripheral motor fibers occurs at all levels, including the
      distal axon. Subclinical involvement of the spinecerebellar tracts, posterior
      column and Clarke's column as well as loss of large neurons in the dorsal root
      ganglia and neurons of oculomotor nuclei has been reported. The average duration
      of life onset of symptoms of amyotrophic lateral sclerosis is three years and
      ninety per cent of patients died within 5 years. The basic mechanism of disease
      in amyotrophic lateral sclerosis remains unknown. There is no known treatment
      that will prevent, reverse or otherwise alter the course of the disease.
      Autosomal dominant and autosomal recessive forms of amyotrophic lateral sclerosis
      are genetic models of amyotrophic lateral sclerosis which may provide insight
      into the disease mechanism of sporadic amyotrophic lateral sclerosis, five to ten
      percent of adult cases of amyotrophic lateral sclerosis with early onset of
      symptoms and a more benign course. It is conceivable that both genetic and
      sporadic forms of amyotrophic lateral sclerosis result from failure of the same
      or similar neuronal mechanism triggered by defective genes and by an environment
      agent in sporadic amyotrophic lateral sclerosis.

PMID- 11980065
TI  - The genetics of idiopathic torsion dystonia.
AB  - The controversy regarding the mode of inheritance of idiopathic torsion dystonia
      in the Ashkenazi Jewish population has been resolved. At one time it was believed
      to be inherited as an autosomal recessive disorder. But recent studies, including
      a prospective, systematic, blinded analysis of the first- and second-degree
      relatives of 43 probands with age at onset less than 28 years found the disorder
      to be inherited in an autosomal dominant manner with a penetrance of
      approximately 0.30. Linkage analysis of Ashkenazi Jewish families with multiple
      affected members revealed that the gene for dystonia in this population is
      located in the q34 region of chromosome 9. This is the same region found to
      encode the dominant DYT1 gene for dystonia in a large non-Jewish family with a
      penetrance of about 0.70. It is likely that the disorder in these two ethnic
      populations may be caused by the same locus, and that the difference in
      penetrance may reflect different mutations operating in these two populations. We
      have found no evidence for genetic heterogeneity in the Ashkenazi Jewish families
      studied for linkage analysis, but there is at least one non-Jewish family with
      idiopathic torsion dystonia that is not linked to this region. Allelic
      association in 9q34 in the Ashkenazi Jewish population has narrowed the dystonia
      gene to a region of less than 2 cM.

PMID- 11980066
TI  - Mapping of the tuberous sclerosis genes.
AB  - Tuberous sclerosis is a dominantly inherited genetic disorder, with a high
      frequency of new mutations, which has been shown through genetic linkage studies
      to be genetically heterogeneous. In this paper we summarize recent progress in
      linkage studies which indicate that there is one TSC gene on chromosome 9q34
      which accounts for approximately 40% of cases and another on chromosome 16p13.3
      which accounts for approximately 50% of cases. We discuss the map position of
      these TSC genes on chromosome 9q34 and 16p13.3. We discuss physical mapping data
      in these two regions. We postulate on the pathogenesis of TSC lesions and on the
      cause of the high frequency of new mutations. We present a strategy to progress
      from the mapping of the TSC genes to isolation of these genes.

PMID- 11980067
TI  - Molecular basis for hyperkalemic periodic paralysis.
AB  - At least one form of periodic paralysis is a direct consequence of a mutation in
      a skeletal muscle, voltage-sensitive sodium channel--it was observed that many
      individual with this disease developed low serum potassium levels during
      paralytic episodes. Some families had hyperkalemic paralysis with serum potassium
      levels of 6 or 7 mEg/L during paralytic crises. In both hypokalemic and
      hyperkalemic paralysis one of the precipitants is a period of rest after
      exertion. In hypokalemic periodic paralysis carbohydrates may initiate weakness.
      In both hyper- and hypokalemic forms, the disorder is inherited as an autosomal
      dominant trait. During hypokalemic and hyperkalemic paralysis, one might
      respectively anticipate muscle hyperpolarization or depolarization. Has been
      observed a potassium-related abnormality of sodium conductance in the
      pathogenesis at least of the hyperkalemic form of periodic paralysis. The fact
      that TTX reverses the physiological defect suggested the hypothesis that the
      primary problem might be a mutation in a TTX-sensitive sodium channel. The
      protein consists of some 2000 amino acids with characteristic intracytoplasmic
      and extracellular domains as well a four remarkably conserved membrane spanning
      domains, each composed of six transmembrane of a polymorphism of the human sodium
      channel with hyperkalemic paralysis. When multipoint analysis was used to test
      for coinheritance of the disease with both Na-2 and growth hormone polymorphisms,
      a lod score of 7 was obtained. That is, the ratio of the probability of linkage
      to non-linkage is 10 million to one. When extracellular potassium is increased to
      10 mM, the affected myotubes demonstrate strikingly abnormal channel behavior
      characterized by prolonged open times or repetitive opens throughout the voltage
      step. Potassium implicate as a primary factor triggering an abnormal sodium
      channel gating mode and, as a result, aberrant sodium current behavior. It was
      estimated that, for the normal channel, the probability of entering a non
      inactivating mode was very low and independent of potassium. On the other hand,
      for the abnormal channel the probability of entering an inactive mode rises up to
      5-fold with hyperkalemic. Four mutations have recently been detected in
      individuals with cold-sensitive paramyotenia congenital. Two of the cause amino
      acid substitutions within the III-IV intracytoplasmic loop. It is striking that
      one substitutes a valine for a glycine. An analysis of the molecular biology of
      each mutation should illuminate not only the disease phenotype but also
      biophysical properties of specific sub-regions of this muscle sodium channel.

PMID- 11980068
TI  - The impact of genetic studies in neurological diseases.

PMID- 11980069
TI  - Charcot-Marie-Tooth disease type 1A: molecular mechanisms of gene dosage and
      point mutation underlying a common inherited peripheral neuropathy.
AB  - Charcot-Marie-Tooth disease type 1A is a demyelinating, inherited peripheral
      neuropathy which is associated with a DNA duplication in chromosome 17p11.2-p12
      in over 70% of patients with CMT1A. The CMT1A duplication is not detected
      cytogenetically, and constitutes a tandem duplication of a 1.5-Mb region of DNA
      flanked by homologous sequences designated as CMT1A-REP. Detection of the CMT1A
      duplication by molecular methods is a valuable diagnostic test for the majority
      of CMT1A cases. This duplication mutation shows stable inheritance through
      multiple generations, and may also arise as a new mutation in sporadic patients.
      The CMT1A duplication leads to the disease phenotype apparently through increased
      dosage of a gene(s) within the duplicated segment. A disease gene associated with
      CMT1A has been identified in the form of PMP22, which maps within the CMT1A
      duplication region, and encodes a myelin protein of the peripheral nerve. Point
      mutations in the PMP22 gene have been identified in CMT1A patients, including one
      case of a new mutation in PMP22 which coincided with the onset of the disease.
      Thus, two alternative molecular mechanisms are responsible for CMT1A: DNA
      duplication leading to increased gene dosage, and point mutation of the PMP22
      gene.

PMID- 11980070
TI  - An ounce of prevention is worth a pound of cure.

PMID- 11980071
TI  - Visual outcome of excimer laser photorefractive keratectomy for myopia. A
      comparison of three laser delivery systems in Australia.
AB  - PURPOSE: To compare the performance of the three excimer laser delivery systems
      in correcting myopia. METHODS: The first generation excimer laser systems
      produced by Summit, VISX and LEI were examined. The first 40 consecutive eyes
      with six-month refractive results were selected from the LEI centre. Forty
      consecutive eyes, matched for age and attempted corrections, were then selected
      from each of the Summit and VISX centres. The postoperative visual results were
      examined retrospectively and compared among the three groups. RESULTS: At six
      month follow-up, the mean and standard deviation of the spherical equivalent
      refraction were +0.27 (SD, 0.65) dioptre in the Summit group, -0.33 (SD, 0.83)
      dioptre in the VISX group and -0.62 (SD, 0.89) dioptre in the LEI group (P =
      0.0001, ANOVA). Thirty-five eyes (88%) in the Summit group, 33 eyes (83%) in the
      VISX group and 28 eyes (70%) in the LEI group achieved corrections within 1
      dioptre of intended corrections (P = 0.131, chi 2 test). Four eyes (10%) in the
      Summit group, two eyes (5%) in the VISX group and one eye (3%) in the LEI group
      were overcorrected by more than 1 dioptre at six-month follow-up. Unaided visual
      acuity (Snellen equivalent) was 6/12 or better in 37 eyes (93%) in the Summit
      group, 34 eyes (85%) in the VISX group and 34 eyes (87%) in the LEI group (data
      missing in one eye). Loss of one or more lines of best corrected visual acuity
      (Snellen equivalent) was found in 6 of 39 eyes (15%) in the Summit group, 10 of
      40 eyes (25%) in the VISX group and 4 of 36 eyes (11%) in the LEI group (P =
      0.258, chi 2 test). Regression between one and six month follow-up differed
      significantly (P = 0.001, ANOVA) among the groups, with the mean of -1.25 (SD,
      0.94) dioptres in the Summit group, -0.59 (SD, 1.01) dioptre in the VISX group
      and -0.40 (SD, 0.99) dioptre in the LEI group. CONCLUSIONS: Statistically
      comparable results were found in the three groups in terms of refraction and
      visual acuity six months after myopic photorefractive keratectomy. No statistical
      differences were found between the groups in terms of significant overcorrection
      or loss of best corrected acuity. The group treated using the Summit system
      demonstrated significantly greater regression than the other groups,
      necessitating larger initial hyperopic shifts.

PMID- 11980072
TI  - A preliminary report on a DNA-based screening method for retinitis pigmentosa. A
      trial on a west Australian population.
AB  - PURPOSE AND BACKGROUND: Recent reports have linked numerous point mutations in
      the human genome to retinitis pigmentosa (RP), suggesting that in the near future
      molecular biology based genetic counselling for patients with RP might become a
      reality. In this paper we assess the viability of a DNA-based screening method
      for RP. Specifically, we screened rhodopsin and the beta-subunit of
      phosphodiesterase (B-PDE) genes for the presence of abnormalities in West
      Australian RP patients. METHODS: Blood was collected from 27 patients. Leukocyte
      DNA was extracted from patients and 50 randomly selected controls. Exons 1-19 and
      21 of B-PDE and exons 1, 3 and 5 of rhodopsin were analysed using single-strand
      conformational polymorphism (SSCP) following DNA amplification. The nature of
      anomalies detected by SSCP was classified with DNA sequencing. RESULTS: In RP
      patient samples, we found anomalous bands in exons 5, 9, 10, 15 and 16 and 17 of
      B-PDE and in exons 1 and 3 of rhodopsin genes. In B-PDE none of the anomalous
      bands represented mutations. Some of the anomalous bands in the rhodopsin gene,
      however, corresponded to silent mutations at nucleotide positions 269 and 3982 in
      four patients. CONCLUSIONS: In this study we have demonstrated that SSCP in
      combination with DNA sequencing is a powerful tool to identify new mutations and
      to provide information for a 'mutational panel' for future screening.

PMID- 11980073
TI  - Validity of the Bruckner reflex in the detection of amblyopia.
AB  - PURPOSE: To establish the sensitivity and specificity of the Bruckner reflex
      (comparison of the fundus red reflexes) in the detection of amblyopia or its risk
      factors. METHODS: A single masked study using a medical student's diagnostic
      ability against the gold standard of a full clinical examination by a paediatric
      ophthalmologist. SETTING: A university teaching hospital outpatient facility.
      PATIENTS: Three hundred and one patients consecutively referred for ophthalmic
      assessment. RESULTS: The sensitivity of the test for the detection of children
      with amblyopia risk factors was 86% and the specificity was 65%. Of 70 children
      with a definite diagnosis of amblyopia, the sensitivity of the test was 95%.
      CONCLUSIONS: The Bruckner reflex is a useful screening test for primary eye care
      personnel. However, there is a significant false-positive rate which will result
      in unnecessary referrals. We recommend that it form part of a battery of tests,
      including, for example, the modified base down prism test, which are useful in
      assessing the vision of preverbal children.

PMID- 11980074
TI  - Prospective study of 210 consecutive cases of endocapsular phacoemulsification
      using the AMO SI-30NB 3-piece foldable lens.
AB  - PURPOSE: To assess the acceptability of clinical outcome achieved with use of the
      SI-30NB lens, as well as the incidence of any lens related complications.
      METHODS: This prospective study evaluated 210 consecutive eyes undergoing
      endocapsular phacoemulsification cataract surgery (EPECS), with implantation of
      the AMO SI-30NB foldable three-piece lens, commencing with the first patient in
      our practice receiving this implant. There was 99% follow-up for at least three
      months, with a mean of nine months, and a range of three to 14 months. Incisions
      were a maximum of 3.2 mm in size, and this allowed minimisation of astigmatism,
      and maximisation of early visual rehabilitation. RESULTS: The final visual acuity
      results were excellent, with 95% of cases achieving corrected vision of 6/12 or
      better. All cases without pre-existing ocular pathology achieved corrected vision
      of 6/6, apart from a single case which achieved 6/9, but the patient died before
      follow-up. The lens-related complication rate was less than 1% (two patients). No
      decentration of any other implant occurred, and no patient complained of edge
      glare. There were no cases of iris chafing or pigment dispersion. Only three
      patients (1.4%) required Yag posterior capsulotomy in the first 14 months of the
      study. Central bag-bag fixation was achieved in 206 of the 210 cases in the study
      (98%). CONCLUSION: The results achieved using the SI-30NB lens with a small
      incision phaco procedure were excellent. Lens-related complications occurred in
      only two cases and very few cases have had problems with posterior capsular
      opacification.

PMID- 11980075
TI  - Exudative macular degeneration and intravitreal triamcinolone. A pilot study.
AB  - PURPOSE: To study the efficacy of the anti-inflammatory agent triamcinolone
      (Kenacort A-40) in patients with exudative age-related macular degeneration and
      subfoveal and juxtafoveal choroidal new vessels, considered unsuitable for laser
      photocoagulation. METHOD: Thirty eyes of 28 patients were treated with
      intravitreal injection of triamcinolone. The subsequent visual acuity (VA) of
      treated eyes was compared with published VA outcomes of untreated eyes. Patients
      were classified into three types according to their responses to treatment.
      RESULTS: Within two weeks of receiving treatment, exudation decreased and vision
      improved in the majority of Types I and II patients (87%), the trend continuing
      in longer term follow-up. The overall VA outcome for treated eyes was
      significantly better than published VA data for untreated exudative macular
      lesions. CONCLUSIONS: The preliminary results are encouraging and no serious side
      effects of a single injection of triamcinolone have been detected in patients
      followed for up to 18 months. The treatment should, however, continue to be
      regarded as unproven and only administered in the context of a prospective, case
      controlled clinical trial.

PMID- 11980076
TI  - Comparison of growth rates of bovine retinal and brain microvascular pericytes in
      different oxygen concentrations in vitro.
AB  - BACKGROUND: The hyperoxic injury of the microcirculation in the central nervous
      system appears to be specific to the retina in premature mammals. Oxygen tensions
      in normal adult mammalian retina and brain vary between nearly 0 and 90 mmHg.
      This study sought to compare the in vitro replication of retinal and brain
      microvascular pericytes in normal glucose medium and in 1%, 5% and 20% oxygen
      (equivalent to 15 mmHg, 35 mmHg and 150 mmHg, respectively). METHODS: A
      preliminary study, using oxygen microelectrodes, confirmed that the pericellular
      oxygen tension of pericytes, cultured in medium under air, was within 13 mmHg of
      the tension of the gas phase above the media. Pericytes were highly enriched by
      magnetic antibody cell sorting with the anti-pericyte monoclonal antibody (3G5)
      to 95% to 99% purity, to remove cell contaminants which may have invalidated the
      mitogenic assay. RESULTS: Mitogenic assays showed that brain pericytes replicated
      faster than their counterparts from retina (P < 0.0001, averaged for data from
      all culture conditions using three-way ANOVA). Reduction of oxygen tension from
      150 to 15 mmHg led to significantly increased replication of retinal pericytes (P
      = 0.01), but an insignificant increase for brain pericytes. CONCLUSIONS: We have
      found that pericytes from the brain and retina cultured conventionally in fetal
      calf serum consume a relatively low amount of oxygen. Decreasing the oxygen
      tension to 1% (15 to 20 mmHg) increased the replication of retinal pericytes but
      not brain pericytes in normal glucose concentrations and in fetal calf serum.
      That retinal pericyte replication is sensitive to variation in oxygen tensions,
      indicates that the retinal microvascular cells have a unique biological response.
      This growth sensitivity to oxygen may be important in the pathogenesis of
      retinopathy of prematurity.

PMID- 11980077
TI  - Congenital ptosis: results of surgical management.
AB  - PURPOSE: To determine the visual and cosmetic outcome following the surgical
      correction of isolated congenital ptosis. METHODS: A retrospective review of the
      outcome of isolated congenital ptosis corrected under the supervision of one
      surgeon at The Children's Hospital, Camperdown, between January 1983 and January
      1993 was examined. Some 65 patients with 80 involved eyes were identified; 30
      eyes underwent a levator resection procedure, 40 eyes underwent a brow suspension
      using donor stored fascia lata, and in 10 eyes a brow suspension was performed
      using mersilene mesh. RESULTS: In 78 eyes of 63 patients, a good cosmetic result
      was achieved. In two patients (two eyes) a poor cosmetic result was achieved.
      These two patients refused further surgery following an undercorrection of their
      initial ptosis. The recurrence rates for the primary procedures were 16.7% for
      levator resection procedures, 35% for brow suspension procedures using donor
      fascia lata, and 30% for brow suspension surgery using mersilene mesh. Some 35.3%
      of eyes following mersilene slings required further surgery for granulomas and
      exposed mersilene mesh compared with 6% having similar complications with stored
      fascia lata. Nine patients (11.25%) had reduced visual acuity (one line or more
      on the Snellen chart or its equivalent with the other tests used) on the operated
      side. Only one patient was found to have significant astigmatism. CONCLUSIONS: An
      acceptable cosmetic result was achieved with one operation in 75.3% of cases. In
      20.8% of cases a second operation was required and in 3.9% of cases three or more
      operations were required. This series supports the view that where possible,
      levator resection is the preferred form of surgery to correct congenital ptosis.
      When the levator function is inadequate, brow suspension is performed. The use of
      donor fascia lata resulted in a good cosmetic appearance with a low occurrence of
      surgical side effects. Amblyopia, when strictly defined, occurred in 11.25% of
      eyes despite early surgery for severe cases and intensive amblyopia therapy.
      Management requires repeated follow up for early detection and introduction of
      occlusion therapy or surgical ptosis correction.

PMID- 11980078
TI  - Clinical exophthalmometry: a comparative study of the Luedde and Hertel
      exophthalmometers.
AB  - Exophthalmometry, the quantitative assessment of the position of the globe in the
      orbit, is a clinically useful measurement. The purpose of this study was to
      examine the performance of a simple exophthalmometer that would lend itself to
      accurate and convenient use in clinical practice. In this study, two observers
      independently performed exophthalmometry on 100 eyes using the Hertel and Luedde
      instruments. The results were compared between instruments and between observers.
      There was no statistically or clinically significant difference between
      measurements taken with the Luedde as compared with the Hertel instrument. The
      Luedde exophthalmometer has a number of advantages over the Hertel
      exophthalmometer, and represents a simple, inexpensive and equally reliable means
      of evaluating clinically the anteroposterior position of the eye in the orbit.

PMID- 11980079
TI  - Uveitis associated with rifabutin therapy.
AB  - PURPOSE: To highlight the association of uveitis with the use of rifabutin.
      METHODS: Retrospective study of two patients with acute anterior uveitis.
      RESULTS: Both patients were receiving rifabutin for treatment of atypical
      Mycobacterium infection associated with AIDS when they developed unilateral acute
      anterior uveitis and arthritis. The inflammation resolved and vision improved
      with introduction of topical corticosteroids, mydriatics and cessation of
      rifabutin treatment. CONCLUSION: Use of rifabutin with clarithromycin may
      precipitate acute uveitis in patients with AIDS being treated for systemic
      Mycobacterium avium complex infection. Uveitis produced by rifabutin may be
      analogous to Herxeimer reaction as seen in syphilis. Clarithromycin and
      fluconazole elevate levels of rifabutin due to inhibition of metabolism through
      cytochrome p-450 pathway. The differential diagnosis includes Reiter's syndrome,
      syphilis causing uveitis, metastatic endophthalmitis, and direct HIV-related
      uveitis.

PMID- 11980080
TI  - Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy.
AB  - BACKGROUND: Haemophilus aphrophilus is a rare cause of ocular infection. It has
      been reported once as a cause of late-onset endophthalmitis in a patient with an
      inadvertent bleb after cataract surgery. We present a case of Haemophilus
      aphrophilus bleb infection after a mitomycin trabeculectomy. METHODS: A 56-year
      old woman presented with a bleb infection 10 weeks after a mitomycin C augmented
      trabeculectomy at a University tertiary referral practice of one of the authors
      (GET). The causative organism was Haemophilus aphrophilus, identified by the
      Toronto Public Health Laboratory, Ontario, Canada. RESULTS: The bleb infection
      resolved following topical, subconjunctival and intravenous antibiotic therapy. A
      formal bleb revision was required to repair a persistent bleb leak. CONCLUSION:
      Patients who have had trabeculectomies augmented with mitomycin C may be
      predisposed to bleb infection with unusual organisms. Prompt diagnosis and
      treatment is necessary to control the infection. Increased awareness and
      communication with laboratory personnel may increase the isolation of this
      fastidious organism.

PMID- 11980081
TI  - Aspergillus sphenoid sinusitis-induced orbital apex syndrome in HIV infection.
AB  - BACKGROUND: Orbital apex syndrome due to aspergillus sphenoid sinusitis is a rare
      condition. Human immunodeficiency virus (HIV) infection has recently been
      reported in aspergillus orbital abscess. To the authors' knowledge this is the
      first reported association of HIV with the orbital apex syndrome. METHODS: A 37
      year-old HIV-infected man presented with headache, reduced vision and progressive
      ophthalmoplegia in the right eye. Computed tomography (CT) and magnetic resonance
      imaging (MRI) revealed sphenoid sinusitis. Sphenoid sinus biopsy was performed.
      RESULTS: Light microscopy revealed infiltrative branching septate fungal hyphae.
      Fungal culture isolated Aspergillus fumigatus. CONCLUSION: Atypical fungal
      infection such as Aspergillus fumigatus sphenoid sinusitis should be suspected in
      HIV-infected patients with orbital apex syndrome.

PMID- 11980082
TI  - Persisting epithelial herpes simplex keratitis while on cyclosporin-A ointment.
AB  - BACKGROUND: This is the first report of cyclosporin-A ointment (CsA) adversely
      affecting epithelial herpes simplex virus keratitis in a corneal graft. METHODS:
      The details of this case were obtained from the patient's record at The Wilmer
      Ophthalmological Institute. RESULTS: Ceasing CsA ointment resulted in resolution
      of the epithelial HSV keratitis. CONCLUSION: Immunosuppression caused by CsA
      ointment resulted in persisting epithelial HSV keratitis despite adequate topical
      treatment.

PMID- 11980083
TI  - A case of seminoma-associated orbitopathy.

PMID- 11980084
TI  - Malignant glaucoma following laser iridotomy.
AB  - BACKGROUND: A 69-year-old man presented with malignant glaucoma 10 days after an
      iridotomy for acute angle-closure glaucoma. METHODS: The case notes are reviewed,
      describing his presentation and treatment, including the technique of
      extracapsular cataract extraction with anterior vitrectomy. RESULTS: An excellent
      visual outcome was achieved with no recurrence of the malignant glaucoma.
      CONCLUSIONS: This case illustrates the recently established link between laser
      iridotomy and malignant glaucoma. Miotics and other possible causes are excluded,
      a surgical option is described and the importance of assessing central anterior
      chamber depth in cases of angle closure is emphasised.

PMID- 11980085
TI  - Multiple endocrine neoplasia type two B. A case report with light and electron
      microscopic and immunohistochemical correlation.
AB  - PURPOSE: To describe a case of multiple endocrine neoplasia type two B (MEN IIB)
      where ocular and systemic clinicopathological findings are correlated, in
      association with light and electron microscopic and immunohistochemical findings.
      METHODS: A 23-year-old man presented with mucosal neuromas of the lips, tongue
      and eyelids, a Marfanoid habitus and prominent corneal nerves. These findings led
      to the diagnosis of multiple endocrine neoplasia type two B. The patient
      subsequently developed phaeochromocytoma and metastatic medullary thyroid
      carcinoma (MTC) which led to his demise. Correlation of light and electron
      microscopic and immunohistochemical findings with the systemic and ocular
      findings is presented to emphasise the aggressiveness of MTC in MEN IIB.
      Clinicopathological correlation was obtained by examining the eyes post mortem.
      RESULTS AND CONCLUSIONS: Three new findings in MEN IIB have been established by
      this study. The enlarged corneal nerves can now be regarded as ganglioneuromas.
      Medullary thyroid carcinoma metastases were found in the choroid. Light and
      electron microscopic examination of the eye showed ganglioneuromas of the nerves
      in the limbus, trabecular meshwork, uveal tract and posterior ciliary nerves;
      this finding may account for the glaucoma occasionally seen in patients with MEN
      IIB.

PMID- 11980086
TI  - Surgical management of involutional entropion.

PMID- 11980088
TI  - Flexible iris retraction hooks.

PMID- 11980087
TI  - The bust of Aubrey Bowen, oculist.
AB  - A fine marble bust of Aubrey Bowen may be seen at The Royal Victorian Eye and Ear
      Hospital. Aubrey Bowen had a distinguished and interesting career which has been
      previously described in the Australian Journal of Ophthalmology. The bust also
      has an interesting history.

PMID- 11980089
TI  - Preoperative hyponatremia as a clinical characteristic in elderly patients with
      large pituitary tumor.
AB  - This study investigated the pathophysiology of preoperative hyponatremia in
      elderly patients with a large pituitary tumor. The tumor size, initial symptoms,
      and preoperative pituitary hormonal function were analyzed in 96 patients,
      consisting of 82 younger than 70 years old (mean age 49.7 years) and 14 older
      than 70 years old (mean age 72.0 years). There was no difference in tumor size
      between the two age groups. The initial symptom of all younger patients was
      visual disturbance. Preoperative hormonal evaluations revealed subclinical
      panhypopituitarism in four patients (4.9%). Five of the 14 older patients had
      severe hyponatremia (107-117 mEq/l) based on panhypopituitarism, and four of
      these five patients showed consciousness disturbance as the initial symptom,
      initiated by physical and/or psychological stress, or occurrence of intratumoral
      hemorrhage. Preoperative subclinical panhypopituitarism was found in another
      patient. The overall occurrence rate of preoperative panhypopituitarism in the
      older patients was 42.9%. The difference in the frequency of preoperative
      panhypopituitarism was statistically significant between the two groups.
      Preoperative severe hyponatremia associated with a large pituitary tumor is
      characteristic of elderly patients. The number of receptors for
      adrenocorticotropic hormone in the adrenal cortex decreases during the aging
      process. Additional physical and/or psychological stress prompts pituitary
      dysfunction in such patients, causing the manifestation of acute symptoms of
      adrenal insufficiency based on panhypopituitarism. Primary care using high dose
      hydrocortisone and electrolyte fluid is critical.

PMID- 11980090
TI  - Transduction efficiency of adenoviral vectors into human glioma cells increased
      by association with cationic liposomes.
AB  - Replication-deficient adenoviral vectors are promising agents for human gene
      therapy of the greater transduction efficiency than other vectors. However, there
      are distinct disadvantages, including high immunogenicity, which limits the
      administration to human organs, particularly the brain. Injection of adenoviral
      vectors into the human brain causes inflammatory responses and induces cerebral
      edema. The combined effect of adenoviral vectors and cationic liposomes in vitro
      was investigated in an effort to reduce the immune reaction against the antigens
      of adenoviral vectors. No toxicity of adenoviral vector-associated liposomes was
      observed within optimal lipid concentration. The transduction efficiency of the
      adenoviral vectors containing the beta-galactosidase gene increased almost 10
      fold when associated with the cationic liposomes. Furthermore, greater
      cytotoxicity was induced when the adenoviral vector containing herpes simplex
      virus-thymidine kinase gene was combined with cationic liposomes than with only
      the adenoviral vector. These results suggest that the combination of adenoviral
      vectors and cationic liposomes allows the doses of adenoviral vectors to be
      reduced while maintaining transduction efficiency.

PMID- 11980091
TI  - Pseudoaneurysm of the superficial temporal artery following craniotomy--case
      report.
AB  - A 48-year-old male without marked blood coagulation disorder developed a
      pseudoaneurysm of the superficial temporal artery (STA) following craniotomy.
      Cerebral angiography revealed a pseudoaneurysm on the parietal branch of the STA.
      Total extirpation was performed, and the postoperative course was uneventful.
      Most pseudoaneurysms of the STA develop after trauma. Lesions rarely develop
      after craniotomy. However, pseudoaneurysm of the STA should be considered as a
      possible surgical complication.

PMID- 11980092
TI  - Pulmonary arteriovenous fistula manifesting as amaurosis fugax--case report.
AB  - Pulmonary arteriovenous fistula (PAVF) is a rare condition which occasionally
      causes neurological complications. A 43-year-old female with multiple PAVFs
      presented with several episodes of amaurosis fugax and transient right
      hemiparesis. She had no other vascular abnormality, and her human leukocyte
      antigen haplotype did not coincide with previous patients with hereditary
      hemorrhagic telangiectasia. She underwent PAVF embolization to prevent further
      neurological complications, and had an uneventful subsequent clinical course.
      Amaurosis fugax is a slight neurological symptom and may be an early important
      sign of PAVF. We stress that PAVFs should be considered in the differential
      diagnosis of patients with amaurosis fugax who complain of exertional dyspnea or
      demonstrate cyanosis.

PMID- 11980093
TI  - Giant aneurysm of the pericallosal artery causing acute subdural hematoma--case
      report.
AB  - A 66-year-old female presented with a very rare giant aneurysm of the distal
      pericallosal artery. She lost consciousness and was admitted. Computed tomography
      demonstrated a subdural hematoma over the left cerebral convexity and a mass in
      the frontal lobe. Cerebral angiography disclosed a giant aneurysm located on the
      distal segment of the right pericallosal artery. The subdural hematoma was
      removed and the aneurysmal neck was clipped, but she died 15 days after the
      operation. Autopsy found the giant aneurysm (33 x 30 x 27 mm) on the distal
      segment of the right pericallosal artery. Highly atheromatous changes were
      recognized in part of the aneurysmal wall, the arteries near the circle of
      Willis, and the distal anterior cerebral artery (ACA) adjacent to the aneurysm.
      There were no anomalous vessels such as azygos ACA. Giant aneurysms situated
      beyond the genu of the corpus callosum are extremely rare. Atherosclerosis was
      probably a major etiological factor in this case.

PMID- 11980094
TI  - Tentorial meningioma associated with pathological laughter--case report.
AB  - A 33-year-old male presented with involuntary and inappropriate laughter.
      Neuroimaging revealed a meningioma ventrolateral to the pons and midbrain,
      attached to the medial middle tentorium on the left side. The pathological
      laughter ceased immediately after subtotal removal of the tumor. Pathological
      laughter may be an early focal sign of a mass compressing ventrolateral
      brainstem.

PMID- 11980095
TI  - Primary malignant lymphoma of the cavernous sinus--case report.
AB  - A 59-year-old female presented with a very rare case of primary malignant
      lymphoma of the cavernous sinus manifesting as diplopia and right facial
      hypesthesia. Magnetic resonance (MR) imaging showed the tumor located in the
      right cavernous sinus as low intensity with marked enhancement by gadolinium. The
      tumor was partially removed by the transzygomatic extradural approach. The
      histological diagnosis was malignant lymphoma. Chest and abdominal computed
      tomography and gallium-67 scintigraphy revealed no other lesions in the body. The
      patient received conventional radiotherapy and her diplopia and right facial
      hypesthesia gradually improved. At 1 month after radiotherapy, MR imaging showed
      no evidence of residual tumor. Primary cavernous sinus malignant lymphoma is
      extremely rare, but should be considered in the differential diagnosis of
      cavernous sinus lesions. Histological confirmation of tumors in this region is
      essential for choosing the most appropriate treatment to achieve a better
      outcome.

PMID- 11980096
TI  - Unusual massive neurinoma in the suboccipital region--case report.
AB  - An 8-year-old boy with no evidence of von Recklinghausen's disease presented with
      an unusual neurinoma manifesting as a gradually progressive swelling in the
      suboccipital region over 2 years. The lesion was massive and had widely eroded
      the posterior aspects of the atlas, axis, and suboccipital bone. The tumor had
      involved the dura of the sigmoid and transverse sinuses, was highly vascular, and
      had encased the ipsilateral vertebral artery. The tumor was almost completely
      resected although with considerable loss of blood through a large rent in the
      right sigmoid sinus. This unusual benign neurinoma most probably arose from the
      second cervical ganglion.

PMID- 11980097
TI  - Pineal region metastasis appearing as hypointensity on T2-weighted magnetic
      resonance imaging--case report.
AB  - A 48-year-old female presented with headache and limitation of upward gaze. She
      had a history of total gastrectomy for gastric adenocarcinoma 2 years previously.
      Computed tomography with contrast medium and T1-weighted magnetic resonance (MR)
      imaging with gadolinium showed ring-like enhancement of a solitary mass in the
      pineal region with obstructive hydrocephalus. T2-weighted MR imaging showed the
      tumor as hypointense. This MR imaging finding complicated the preoperative
      diagnosis, but malignancy was suspected from the medical history. The tumor was
      subtotally resected via the occipital transtentorial approach with a rigid
      endoscope. Histological examination of the surgical specimen revealed
      adenocarcinoma cells with extensive coagulation necrosis, which might have
      contributed to the hypointensity on T2-weighted MR imaging. Correct diagnosis of
      metastatic adenocarcinoma based only on MR imaging may be difficult in such
      cases, but metastatic adenocarcinoma of the pineal region must be considered in
      the differential diagnosis of pineal tumors.

PMID- 11980098
TI  - Cerebral blood flow during plateau waves in a patient with benign intracranial
      hypertension--case report.
AB  - A 50-year-old male presented with benign intracranial hypertension (BIH). He was
      admitted to our hospital for headache and papilledema. The diagnosis was BIH as
      continuous monitoring of lumbar cerebrospinal fluid pressure (CSFP) showed high
      basal pressure with intermittent plateau waves. Ten months after successful
      ventriculoperitoneal shunting, he presented with headache again due to shunt
      malfunction. CSFP monitoring showed the same findings as before. Regional
      cerebral blood flow (rCBF) was measured by positron emission tomography (PET)
      using the 15O-labeled water autoradiographic method with simultaneous recording
      of lumbar CSFP. The rCBF values of the cerebral cortex, white matter, thalamus,
      cerebellar cortex, and pons were evaluated during both the plateau waves and the
      intervals. In spite of severely reduced cerebral perfusion pressure, rCBF during
      the plateau waves was not reduced when compared with the rCBF of normal
      volunteers in all regions. This result might explain why patients with BIH show
      no impairment of consciousness or focal signs during the plateau waves.

PMID- 11980099
TI  - Development of a multiple regression model to identify multi-family residential
      buildings with a high prevalence of sick building syndrome (SBS).
AB  - The aim was to develop a multiple logistic regression model to identify multi
      family houses with an increase of sick building syndrome (SBS). In Stockholm, 609
      multi-family buildings with 14,235 dwellings were selected by stratified random
      sampling. The response rate was 77%. Multiple logistic regression analysis was
      applied, adjusting for ownership of the building, building age and size, age,
      gender, and atopy. Females, subjects with allergy, those above 65 yr, and those
      in new buildings reported significantly more SBS. Subjects owning their own
      building reported less SBS, but the relationship between ownership and building
      age was strong. A regression model, including factors with a high explanatory
      value was developed. According to the model, 5% of all buildings built before
      1961, 13% of those built 1976-1984, and 15% of those built 1985-1990 would have
      significantly more SBS than expected. In conclusion, SBS is related to personal
      factors, building age, and ownership of the building. To identify multi-family
      buildings with more SBS than expected, it is necessary to adjust for ownership
      and population characteristics.

PMID- 11980100
TI  - The relationship between measured moisture conditions and fungal concentrations
      in water-damaged building materials.
AB  - We determined the moisture levels, relative humidity (RH) or moisture content
      (MC) of materials, and concentrations of culturable fungi, actinomycetes and
      total spores as well as a composition of fungal flora in 122 building material
      samples collected from 18 moisture problem buildings. The purpose of this work
      was to clarify if the is any correlation between the moisture parameters and
      microbial levels or generic composition depending on the type of materials and
      the time passed after a water damage. The results showed an agreement between the
      concentrations of total spores and culturable fungi for the wood, wood-based and
      gypsum board samples (r > 0.47). The concentrations of total spores and/or
      culturable fungi correlated with RH of materials particularly among the wood and
      insulation materials (r > 0.79), but not usually with MC (r < 0.45). For the
      samples collected from ongoing damage, there was a correlation between RH of
      materials and the concentrations of total spores and culturable fungi (r > 0.51),
      while such a relationship could not be observed for the samples taken from dry
      damage. A wide range of fungal species were found in the samples from ongoing
      damage, whereas Penicillia and in some cases yeasts dominated the fungal flora in
      the dry samples. This study indicates that fungal contamination can be evaluated
      on the basis of moisture measurements of constructions in ongoing damage, but the
      measurements are not solely adequate for estimation of possible microbial growth
      in dry damage.

PMID- 11980101
TI  - Nicotine and 3-ethenylpyridine concentrations as markers for environmental
      tobacco smoke in restaurants.
AB  - The Finnish Tobacco Act has restricted smoking in public places since 1976, and
      in 1994 the Act was amended to include workplaces as well. In 2000, the Tobacco
      Act will be expanded further to restaurants. In Finland, the exposure of clients
      and employees to the vapor phase environmental tobacco smoke (ETS) in restaurants
      has not been systematically studied before by measuring ETS markers in indoor
      air. However, in these establishments the concentrations of ETS are expected to
      be much higher than in other workplaces. Gaseous nicotine and 3-ethenylpyridine
      were used as indicators of ETS in three different types of restaurants. Mean
      concentrations of nicotine ranged from 1.4-42.2 micrograms/m3 and 3
      ethenylpyridine 1.4-6.3 micrograms/m3. In addition, concentrations of total
      volatile organic compounds (TVOC), CO and CO2 were measured and concentrations
      were 183-2215 micrograms/m3, 0.9-3.1 mg/m3 and 600-880 ppm, respectively. The
      concentrations of ETS markers were highest in discos and nightclubs and lowest in
      restaurants. The concentrations of total volatile organic compounds were highest
      in discos and nightclubs, especially when smoke generators were used.

PMID- 11980102
TI  - Penetration of nitrogen oxides and particles from outdoor into indoor air and
      removal of the pollutants through filtration of incoming air.
AB  - We studied the effect of ventilation and air filtration systems on indoor air
      quality in a children's day-care center in Finland. Ambient air nitrogen oxides
      (NO, NO2) and particles (TSP, PM10) were simultaneously measured outdoors and
      indoors with automatic nitrogen oxide analyzers and dust monitoring. Without
      filtration nitrogen oxides and particulate matter generated by nearby motor
      traffic penetrated readily indoors. With chemical filtration 50-70% of nitrogen
      oxides could be removed. Mechanical ventilation and filtration also reduced
      indoor particle levels. During holidays and weekends when there was no opening of
      doors and windows and no particle-generating activity indoors, the indoor
      particle level was reduced to less than 10% of the outdoor level. At times when
      outdoor particle concentrations were high during weekdays, the indoor level was
      about 25% of the outdoor level. Thus, the possible adverse health effects of
      nitrogen oxides and particles indoors could be countered by efficient filtration.
      We also showed that inclusion of heat recovery equipment can make new ventilation
      installations economical.

PMID- 11980103
TI  - Release of acetic acid and furfural from cork products.
AB  - Cork samples were exposed to different temperatures and volatile ingredients were
      analyzed using gas chromatography/mass spectrometry (GC/MS). Thermal treatment at
      180 degrees C yielded considerable amounts of furfural and acetic acid. In
      accordance with previous investigations it was concluded that both compounds are
      produced under thermal stress from degradation of polyoses.

PMID- 11980104
TI  - Indoor air quality in the 21st century: search for excellence.
AB  - Field studies demonstrate that there are substantial numbers of dissatisfied
      people in many buildings, among them those suffering from sick building syndrome
      (SBS) symptoms, even though existing standards and guidelines are met. The reason
      is that the requirements specified in these standards are rather low, allowing a
      substantial group of people to become dissatisfied and to be adversely affected.
      A paradigm shift from rather mediocre to excellent indoor environments is
      foreseen in the 21st century. Based on existing information and on new research
      results, five principles are suggested as elements behind a new philosophy of
      excellence: 1) better indoor air quality increases productivity and decreases SBS
      symptoms; 2) unnecessary indoor pollution sources should be avoided; 3) the air
      should be served cool and dry to the occupants; 4) "personalized air", i.e. a
      small amount of clean air, should be served gently, close to the breathing zone
      of each individual; and 5) individual control of the thermal environment should
      be provided. These principles of excellence are compatible with energy efficiency
      and sustainability.

PMID- 11980105
TI  - Microbiology on indoor air '99--what is new and interesting? An overview of
      selected papers presented in Edinburgh, August, 1999.
AB  - A multidisciplinary approach to microbiological implications of indoor air is
      fruitful for research as well as management of health and building problems. The
      Finnish and the Danish mold programs are examples of such productive
      collaborative studies. Dust samples taken from classrooms in schools where
      occupants complain of building-related symptoms (BRS) demonstrated an
      inflammatory potential in vitro, measured as a release of cytokine interleukin
      (IL)-8. An increase of the metabolite NO and liberation of tumor necrosis factor
      (TNF)-alpha and other cytokines during exposure were obtained in vivo, was
      presented based on these programs and on epidemiological studies on residential
      fungal contamination and health conducted in Canada and The Netherlands. New
      methods for assessing fungal exposure are PCA analysis for the toxigenic mold
      Stachybotrys chartarum and EPS-Asp/Pen for detecting of Aspergillus and
      Penicillium in dust. Based on a limited data set it is shown that emission rates
      of fungal spores are inversely proportional to relative humidity (RH), directly
      related to flow rate and to surface loading. Poor maintenance, risk constructions
      and risk materials are described in several studies as the main causes of water
      damage in buildings.

PMID- 11980106
TI  - Formation of strong airway irritants in terpene/ozone mixtures.
AB  - The American Society for Testing and Materials (ASTM) mouse bioassay, which
      quantifies airway irritation from reduction in the respiratory rate, was used to
      find evidence for the formation of highly irritating substances in reactions of
      ozone with terpenes (common indoor volatile organic compounds (VOCs)). No
      observed-effect-levels (NOELs) and concentration-effect relationships were
      established for ozone, (+)-alpha-pinene and R-(+)-limonene, isoprene, and some of
      their major reaction products. Reaction mixtures of excess terpene and ozone
      considerably below their NOEL concentrations resulted in significant upper airway
      irritation. The reduction of the respiratory rate was from 30% to about 50%,
      lowest for the alpha-pinene and highest for the isoprene mixture. Chemical
      analysis of reaction mixtures by conventional methods showed that readily
      identified stable products and residual reactants at the concentrations found
      could not account for the observed reductions of the respiratory rate, assuming
      additivity of the reaction products. The results suggest that, in addition to
      known irritants (formaldehyde, acrolein, methacrolein, methyl vinylketone), one
      or more strong airway irritant(s) of unknown structure(s) were formed. Future
      indoor air quality (IAQ) guidelines for unsaturated VOCs (e.g., terpenes) and
      their emission from building products may require the consideration of reactions
      with oxidants, like ozone. Similarly, effects of ozone-emitting equipment should
      be re-evaluated.

PMID- 11980107
TI  - The influence of ventilation on reactions among indoor pollutants: modeling and
      experimental observations.
AB  - This study examines the influence of ventilation on chemical reactions among
      indoor pollutants. We have used a one compartment mass balance model to simulate
      unimolecular and bimolecular reactions occurring indoors. The initial modeling
      assumes steady-state conditions. However, at low air exchange rates, there may be
      insufficient time to achieve steady-state. Hence we have also modeled non steady
      state scenarios. In the cases examined, the results demonstrate that the
      concentrations of products generated from reactions among indoor pollutants
      increase as the ventilation rate decreases. This is true for unimolecular and
      bimolecular reactions, regardless of whether the pollutants have indoor or
      outdoor sources. It is also true even when one of the pollutants has an outdoor
      concentration that displays large diurnal variations. We have supplemented the
      modeling studies with a series of experiments conducted in typical commercial
      offices. The reaction examined was that between ozone and limonene. The ozone was
      present as a consequence of outdoor-to-indoor transport while the limonene
      originated indoors. Results were obtained for low and high ventilation rates.
      Consistent with the modeling studies, the concentrations of monitored products
      were much larger at the lower ventilation rates (even though the ozone
      concentrations were lower). The potential for reactions among indoor pollutants
      to generate reactive and irritating products is an additional reason to maintain
      adequate ventilation in indoor environments.

PMID- 11980108
TI  - "What happens when care isn't safe?".

PMID- 11980109
TI  - "Domestic violence".
AB  - Domestic violence is no respector of persons but may involve spouses or
      cohabiting adults across all socioeconomic, ethnic, and religious groups. It is
      no respect or of community. The abuse can be physical, sexual, or
      emotional/psychological. It can be economic and be demonstrated by neglect.
      Nursing care for the problem of domestic abuse needs to be directed at primary,
      secondary, and tertiary prevention. Care for victims and victimizers of domestic
      violence involves a collaborative relationship with other professionals as well
      as interagency cross referrals that involve health, welfare, refuge, and judicial
      protective services.

PMID- 11980110
TI  - Cornwall & Isles of Scilly Health Community.

PMID- 11980111
TI  - [Effectiveness of detection of bronchial asthma with two international
      questionnaires].
AB  - AIM: Assessment of two questionnaires (ECRHS and IUATLD) for efficiency in
      bronchial asthma (BA) detection. MATERIAL AND METHODS: 196 patients aged 16-59
      years seeking advice of a doctor for pulmonary or extrapulmonary complaints. All
      of them have not been previously examined for BA. At first stage of the study the
      patients filled in ECRHS and IUATLD questionnaires. At the second stage patients
      who had answered positively as least one question of the above questionnaires
      underwent clinical, functional and allergological examinations. RESULTS: BA was
      more frequently detected in patients with chronic bronchopulmonary and allergic
      diseases. New cases with mild disease predominated. CONCLUSION: Both
      questionnaires were effective for BA diagnosis but ECRHS showed a number of
      advantages which make it preferable for epidemiological surveys.

PMID- 11980112
TI  - [Erythrocyte insulin-reactive system and carbohydrate metabolism in bronchial
      asthma].
AB  - AIM: Analysis of insulin-reactive system of erythrocytes and carbohydrate
      metabolism in bronchial asthma (BA) at cell and other levels. MATERIAL AND
      METHODS: 106 patients with BA, 26 healthy subjects and 10 healthy subjects with
      familial history of atopy participated in the study. Glucose tolerance and
      colorimetric tests were made to measure glucose, glycosylated hemoglobin,
      respectively. Erythrocytic insulin reactivity was assessed using an original
      method. Bronchial resistance was determined and specific bronchial conduction was
      calculated. Acetylcholine test was conducted before and after a single inhalation
      of 5% isoosmolar glucose solution. RESULTS: Atopic BA was characterized by a
      trend to hypoglycemia, low glycosylation of red cell hemoglobin, impaired
      membrane transport of glucose in red cells, a hypoglycemic type of glucose
      tolerance test curve, a paradoxical reaction of erythrocytes to insulin and
      adrenaline--release of glucose. CONCLUSION: The detected changes in cell insulin
      reactivity in atopic BA and positive effects of 5% glucose solution inhalations
      on bronchial hyperreactivity in BA patients provide grounds for development of
      new therapeutic approaches in BA.

PMID- 11980113
TI  - [Pharmacodynamics of inhalation broncholytic agents introduced in a single dose
      by nebulizer in patients with severe exacerbation of bronchial asthma].
AB  - AIM: To study pharmacodynamics and safety of inhalatory beta-2-adrenostimulators
      and M-cholinolytics given via nebulizer in patients with severe exacerbation of
      bronchial asthma (BA). MATERIAL AND METHODS: The study covered 78 patients with
      severe exacerbation of BA (mean age--48.6 +/- 15.0 years). The patients were
      randomized into 4 groups: 23, 20, 18 and 17 patients, respectively. They were
      treated with: ventolin nebuly (2.5 mg), berodual (0.25 mg ipratropium bromide and
      0.5 mg phenoterol), atrovent (0.5 mg), berotek (1.0 mg by nebulizer Pulmo-Aide
      56501). Efficiency and safety of the treatment was assessed by the data of
      external respiration function, arterial blood gases and ECG each 30 min for 3
      hours. RESULTS: In patients with severe exacerbation of BA pharmacodynamics of
      all the studied drugs was characterized by less duration and potency of the
      action. Salbutamol and berotek were effective for 180 min, atrovent--for 30-60
      min. Inhalation broncholytics had no such serious side effects as prolongation of
      corrected interval Q-T or onset of arrhythmia. Berotek demonstrated longer action
      on heart rate than salbutamol. CONCLUSION: Severe complication of BA is treated
      more effectively with combination of beta 2-adrenomimetic with atrovent.

PMID- 11980114
TI  - [Clinical and biochemical aspects of flixotide administration in patients with
      moderate bronchial asthma].
AB  - AIM: To compare clinical, device and biochemical aspects of monotherapy with
      flixotide vs combination of flixotide with serevent in patients with moderate
      bronchial asthma (MBA). MATERIAL AND METHODS: 18 patients with MBA received
      flixotide and 18 MBA patients flixotide plus serevent for two weeks of lead-in
      and eight weeks of basic treatment. A special study was made of neutrophils which
      were examined for activity of LPO-antioxidants and phospholipid spectrum of
      membranes. RESULTS: There were similar changes in function of the system LPO
      antioxidants and lipid structure in neutrophilic membranes of moderate BA
      patients of both the groups. CONCLUSION: Clinicobiochemical efficacy of mean
      doses of a new topic inhalation glucocorticoid flixotide alone or in combination
      with prolonged beta 2-adrenostimulator serevent is demonstrated. There were
      positive trends in metabolic processes in neurophilic membrane. Use of flixotide
      in combination with serevent is clinically preferable.

PMID- 11980115
TI  - [Efficacy of low intensity laser irradiation and sodium nedocromil in the complex
      treatment of patients with bronchial asthma].
AB  - AIM: To study efficiency of low-intensity laser radiation (LILR) and sodium
      nedokromil (tailed) in combined treatment of bronchial asthma (BA). MATERIAL AND
      METHODS: The choice of the treatment depended on the activity of bronchial
      inflammation and the presence of contraindications. Laser was used on the skin in
      the area of the lung and great vessels projection, endobronchially. Tailed was
      given in inhalations and irrigations of the tracheobronchial tree during
      therapeutic fibrobronchoscopy. These methods were used in combined treatment of
      220 BA patients. RESULTS: Combined use of LILR and tailed proved highly effective
      and safe in BA. Cytological markers of cell reactions of the bronchopulmonary
      system on the action of LILR were revealed. CONCLUSION: Availability, good
      reproducability, cost-effect efficacy and safety make LILR one of the most
      beneficial nonpharmacological treatments for bronchial asthma.

PMID- 11980116
TI  - [Efficacy and safety of high doses of beclomethasone dipropionate in patients
      with bronchial asthma].
AB  - AIM: To assess efficiency and safety of high-dose beklometasone dipropionate in
      patients with bronchial asthma (BA). MATERIAL AND METHODS: The trial included 14
      female and 3 male patients with moderate or severe BA (mean age 43.6 years) in
      declining exacerbation. The patients inhaled beklometasone dipropionate as a dose
      adjusted aerosol with built-up spacer (beklojet) in a daily dose 1000-2000 mcg
      for 8 weeks. Changes in clinical symptoms, life quality (AQLQ) and bronchial
      permeability (peak flowmetry, FEV1) were registered. Concentration of H2O2 in
      expired air condensate was measured spectrophotometrically to evaluate activity
      of airway inflammation. Oral smears were studied mycologically, hydrocortisone in
      blood plasma was measured with enzyme immunoassay. RESULTS: The treatment
      produced positive trend in clinical symptoms and quality of life. Bronchial
      permeability improved since the 7th treatment day. H2O2 significantly fell,
      hydrocortisone levels and fungal flora did not change significantly. CONCLUSION:
      Beklometasone dipropionate in high doses for 8 weeks is effective and safe
      against BA.

PMID- 11980117
TI  - [Alphacalcidol in the treatment of osteopenic syndrome in patients with bronchial
      asthma].
AB  - AIM: To assess effectiveness of alphacalcidol in the treatment of osteopenic
      syndrome in patients with bronchial asthma (BA). MATERIAL AND METHODS: 65 BA
      patients with low densitometric parameters of bone tissue density were examined
      for bone density, basic parameters of Ca-P metabolism and some markers of bone
      metabolism during 6-month therapy with alphacalcidol (alpha-D3-TEVA) in a dose
      0.5-0.75 mcg/day. RESULTS: All the patients after 6 months of therapy experienced
      pain relief, normalization of calcium-phosphorus metabolism, lower risk of broken
      bones. Their bone tissue increased its density. CONCLUSION: Alphacalcidol has
      analgetic and antiresorptive properties. It effectively prevents and treats
      osteopenic syndrome in patients with bronchial asthma.

PMID- 11980118
TI  - [Clinical aspects of tracheobronchial dyskinesia].

PMID- 11980119
TI  - [Pharmacoeconomic aspects in the treatment of chronic obstructive bronchitis].
AB  - AIM: Analysis of pharmacological cost-efficiency at various stages of medical
      care for patients with chronic obstructive bronchitis (COB). MATERIAL AND
      METHODS: The cost of COB patients treatment, including that of hospital stay,
      ambulance call, outpatient treatment, cost of medicines. RESULTS: In direct
      medical expenditures, the cost of hospital stay is the highest. Most of this
      money (80%) is spent on management of severe exacerbation of COB in critical care
      units. CONCLUSION: It would be valid to set up specialized outpatient service for
      follow-up and treatment of COB patients.

PMID- 11980120
TI  - [Parameters of membrane permeability, microcirculation, external respiration, and
      trace element levels in the drug-laser treatment of pneumonia].
AB  - AIM: To study effects of laser therapy in combined treatment of pneumonia on
      external respiration function, membrane permeability, microcirculation and serum
      trace elements. MATERIAL AND METHODS: 142 pneumonia patients were randomly
      divided into two groups: 96 patients treated with drugs and laser radiation (the
      study group) and 46 patients treated with drugs only (control group). RESULTS: In
      the study group there was more pronounced reduction in cell membrane
      permeability, a rise in concentrations of iron and chromium in the blood serum,
      improvement of microcirculation. These changes closely correlated with those in
      immunity, external respiration function. CONCLUSION: Laser therapy is an
      effective method of pneumonia treatment and can be included in relevant combined
      schemes.

PMID- 11980121
TI  - [Microcirculation and hemostasis in influenza and acute viral respiratory
      infections complicated with pneumonia].
AB  - AIM: To study microcirculation (MC), hemostasis and blood viscosity (BV) in
      influenza and acute respiratory viral infections (ARVI) complicated by pneumonia.
      MATERIAL AND METHODS: Conjunctival biomicroscopy, hemostasis and BV were studied
      in 232 patients with influenza and ARVI. In 91 of them the disease complicated
      with acute pneumonia (AP), in 87--with obstructive bronchitis. RESULTS:
      Irrespectively of the disease course, patients with influenza and ARVI showed
      intravascular changes in MC system, hypercoagulation, deterioration of
      fibrinolysis. In convalescence platelet aggregation increased, fibrinolytic blood
      activity enhanced. In influenza and ARVI complicated with AP intravascular
      changes and hypercoagulation were most pronounced. In uncomplicated influenza and
      ARVI accompanied by bronchitis such changes are less severe. BV was the highest
      in development of AP. CONCLUSION: MC and hemostatic disorders arising in
      influenza and ARVI seem to be essential pathogenetic links provoking development
      of AP. In intravascular aggregation of platelets and red cells, activation of
      plasmic hemostasis differentiated treatment with desaggregants and anticoagulants
      are indicated.

PMID- 11980123
TI  - [Primary systemic and pulmonary vasculitis].

PMID- 11980122
TI  - [Effect of halogen aerosol therapy on resistance parameters of the respiratory
      tract].
AB  - AIM: Assessment of the efficacy of dry high-dispersive aerosol of sodium chloride
      -the main acting factor of haloaerosol therapy--on defense system of the
      respiratory tract. MATERIAL AND METHODS: 188 patients with respiratory disease
      and at risk of pulmonary pathology received course of haloaerosol therapy. 49
      matched patients were given placebo. The effect of the treatment was assessed by
      clinicoendoscopic picture, cytomorphological and bacteriological characteristics
      of the bronchoalveolar lavage, contamination activity of the microflora, activity
      of local humoral immunity in pharyngeal brush-biopsies and saliva, rheological
      indices of the sputum. RESULTS: Dry aerosol of sodium chloride demonstrated
      antiinflammatory activity in the respiratory tract, mucoregulating action. It
      enhances drainage of the bronchi, activates alveolar macrophages, improves
      biocenosis and local humoral immunity. CONCLUSION: Haloaerosol therapy has
      positive effect on the defense system, improves function of the respiratory
      tracts.

PMID- 11980124
TI  - [Cardiorespiratory system in adult patients with mucoviscidosis].
AB  - AIM: To study cardiorespiratory system in adult patients with mucoviscedosis.
      MATERIAL AND METHODS: External respiration function, echocardiographic and
      dopplercardiographic evidence were analysed for 22 patients with mucoviscedosis.
      RESULTS: 66.7% examinees had mixed pulmonary ventilation disorders, 46% were
      found to have low diffuse capacity of the lungs correlating in degree with
      ventilatory abnormalities. Dilated right heart and high systolic pressure in the
      pulmonary artery were registered in 14% patients with marked obstruction. Left
      ventricular systolic and diastolic defects occurred in 23%. CONCLUSION: Adult
      patients with mucoviscedosis have mixed disorders of pulmonary ventilation, high
      pressure in pulmonary circulation and developing pulmonary heart in patients with
      severe obstruction.

PMID- 11980125
TI  - [Likopid in the complex immunomodulating treatment of patients with sarcoidosis
      of the lung and intrathoracic lymph nodes].
AB  - AIM: To examine the functional status of the immune system in patients with lung
      and intrathoracic lymph nodes sarcoidosis and to evaluate the efficiency of
      immunomodulation alone and in its inclusion in combined treatment of the disease.
      MATERIALS AND METHODS: 58 patients with the disease of varying severity were
      followed up. Comprehensive examination, involving clinical, immunological, X-ray,
      and physical studies, in patients treated with combined immunotherapy was
      performed. Initial examination revealed mixed immunodefficiency with impaired T-
      and phagocytic activity. According to the degree of immunological changes, the
      patients were given immunotherapy, including polyoxidonium, T-activin (or
      immunophan) injections, a complex of multivitamins and trace elements, and total
      adaptogens. After partial or complete normalization of an immunogram, all the
      patients received licopid (two-three 10-day courses, 10 mg/day). RESULTS: The
      optimal result (as long as 3-year remission) was achieved in the first time
      diagnosed sarcoidosis who have not taken glucocorticoidal hormones. CONCLUSION:
      The follow-up shows that addition of licopid is a compulsory component of
      immunotherapy in this disease; the efficiency of treatment is determined by its
      multimodality. The courses of therapy should be repeated when immunological
      indices deteriorated.

PMID- 11980126
TI  - [24-Hour arterial pressure profile in chronic obstructive lung diseases in
      combination with arterial hypertension treated with enalapril].
AB  - AIM: To evaluate peculiarities and trends in 24-hour arterial pressure (AP)
      profile and bronchoobstructive syndrome (BOS) in patients with chronic
      obstructive pulmonary diseases (COPD) and arterial hypertension (AH) on combined
      treatment including enalapril maleate. MATERIAL AND METHODS: Changes in BOS as
      shown by clinical data, data of peakflowmetry and external respiration function
      as well as in AP 24-hour profile according to 24-hour monitoring were studied in
      50 patients with exacerbation of bronchial asthma and chronic bronchitis treated
      for 4 weeks with conventional broncholytic and antiinflammatory modalities, in 28
      patients with mild and moderate AH receiving combined therapy including enalapril
      maleate. RESULTS: In exacerbation of COPD, 24-h AP profile is characterized by
      high frequency of the curve "non-dipper". Concomitant mild and moderate AH was
      diagnosed in more than half of the examinees. The addition of enalaprile maleate
      to the treatment in many cases lowered systolic and diastolic AP, normalized
      sympathicoadrenal system and 24-hour AP rhythm, reduced dyspnea, improved
      exercise tolerance, sleep. Good tolerance of the drug was seen in patients with
      exacerbation of COPD. CONCLUSION: In exacerbation of COPD it is recommended to
      monitor AP for 24 hours for early detection of AH and initiation of combined
      treatment with correction of bronchoobstructive syndrome and hemodynamic
      disorders. As a hypotensive drug, enalapril maleate is adequate in such patients.

PMID- 11980127
TI  - [N-Acetylcysteine: low and high doses in the treatment of chronic obstructive
      lung diseases in Chernobyl accident liquidators].
AB  - AIM: To study clinical effectiveness and antioxidant activity of N-acetylcisteine
      (NAC) in daily doses 600, 1200, 1800 and 2400 mg in Chernobyl wreckers suffering
      from chronic obstructive pulmonary diseases (COPD). MATERIAL AND METHODS: Cough
      intensity and expectoration, malonic dialdehyde (MD), plasma calcium ions
      concentrations were studied in patients taking NAC. RESULTS: Cough intensity
      diminished insignificantly. Expectoration improved significantly only after
      intake of 1200 mg/day NAC. In higher doses expectoration difficulties appeared
      again. Five patients received a maintenance dose 200 mg/day as a result of which
      their expectoration improved. MDA in the above patients was 3.3 times higher than
      normal level, free calcium ion concentration was 1.7 times higher. Only 1200
      mg/day dose of NAC brought MDA level to normal, higher doses made it subnormal.
      Calcium ions concentration decreased but insignificantly. Maintenance dose 200
      mg/day returned MDA and calcium to initial level. CONCLUSION: For patients with
      radiation-induced affection of the respiratory tracts NAC dose 1200 mg/day is
      optimal both clinically and in terms of antioxidant activity.

PMID- 11980128
TI  - [A case of familial primary pulmonary hypertension].

PMID- 11980129
TI  - [Comparative antihistamine and anti-allergic effects of various antihistamine
      preparations].
AB  - AIM: To compare antihistaminic and antiallergic activity of antihistaminic drugs
      of the latest generation (ebastin, cetirisine, fexofenadine, loratadine) and
      antihistaminic drugs of the first generation (clemastin) in the same patients
      with pollenosis. MATERIAL AND METHODS: Skin prick-titration with 10-dilution
      histamine and specific allergen, provocative nasal titration with 2-dilution
      histamine and allergen before and after a single intake of H1-antagonists were
      made in 30 patients in stable clinical remission of pollenosis during maximal
      antihistamine activity of the above drugs. RESULTS: Systemic administration of
      the known H1-antagonists suppresses histamine sensitivity of both skin and nasal
      mucosa in the same degree. Drugs with more potent antihistaminic activity
      (fexofenadin and cetirisin) inhibited allergen-induced reactions more
      effectively. The order of the tested drugs by suppression of allergen-provoked
      skin and nasal reactions (by lowering antiallergic activity) is the following:
      fexofenadin and cetirisin > ebastin and loratadin > clemastin. CONCLUSION: The
      above drugs of the latest generation seem to posses antiallergic activity not
      only due to antihistaminic effect but also due to other mechanisms. Different
      suppressive action of H1-antagonists reflects also individual sensitivity to
      different drugs. The factor of individual sensitivity of the patients to a
      pharmacological action of the drug may be crucial in the selection of the most
      effective medicine for each patient. This is confirmed by the data of individual
      sensitivity of the patient to antihistaminic and antiallergic action of H1
      antagonists. The illustrated method may be helpful for individual selection of H1
      antagonists for treatment of patients with allergic diseases.

PMID- 11980130
TI  - [Relationship between various clinical parameters and duration and variability of
      Q-T and R-R intervals in ECG (an epidemiological population study)].
AB  - AIM: To study the relationship between clinical values of a standard
      epidemiological study of a male population and the length and variability of Q-T
      and R-R intervals. MATERIAL AND METHODS: A representative sampling from a male
      population (2184 subjects aged 25-64 years) in Novosibirsk was examined using
      standard epidemiological methods. Later 251 men were excluded from the study
      because of impossibility of correct analysis of ECG. The length and dispersion of
      Q-T interval and time parameters of variability of R-R interval were evaluated.
      RESULTS: The size and variability of Q-T and R-R intervals are associated with
      age and AP irrespective of other clinical parameters of a simultaneous
      epidemiological study. The length of R-R interval is independently related to
      body weight index, tobacco smoking, and plasma triglyceride level. R-R
      variability parameters are associated with coronary disease irrespective of the
      risk factors. CONCLUSION: Scanning studies with complex analysis of Q-T and R-R
      interval duration and variability effectively detect subjects at a high risk of
      arrhythmias and fatal events.

PMID- 11980131
TI  - [Hypotensive effect of long-acting garlic tablets allicor (a double-blind placebo
      controlled trial)].
AB  - AIM: To evaluate a hypotensive action of long-acting garlic powder tablets
      allicor in patients with mild or moderate hypertension and to compare allicor
      effects with those of foreign analog--kwai garlic tablets. MATERIAL AND METHODS:
      A double-blind, randomized and placebo-controlled study enrolled 85 patients with
      mild or moderate hypertension. The patients were divided into 4 groups: group 1
      received allicor in a dose 600 mg/day, group 2--2400 mg/day, group 3--kwai in a
      dose 900 mg/day, group 4--placebo. RESULTS: Allicor produced reaction in both
      systolic and diastolic pressure. An increase of allicor daily dose to 2400 mg
      does not provide an additional hypotensive effect. Kwai results in only systolic
      but not diastolic arterial pressure lowering. CONCLUSION: Allicor is more
      effective than kwai in reduction of diastolic blood pressure. It can be
      recommended as a hypotensive treatment in mild and moderate arterial
      hypertension.

PMID- 11980132
TI  - [Pharmacokinetic of prednisolone in patients with rheumatoid arthritis].
AB  - AIM: To study pharmacokinetics of prednisolone in patients with rheumatoid
      arthritis (RA). MATERIAL AND METHODS: The examination of 10 RA patients included
      blood tests for glucocorticoids 1, 2, 4 and 6 hours after the drug intake. Serum
      steroids were measured using high performance liquid chromatography.
      Pharmacokinetic parameters were estimated in one-chamber model with absorption.
      RESULTS: In spite of the same dose of prednisolone, its serum concentration as
      well as pharmacokinetic parameters were individual in each patient. CONCLUSION:
      Pharmacokinetic indices of prednisolone in RA patients provide more reliable
      information for design of treatment scheme for each patient individually.

PMID- 11980133
TI  - [Current approaches to prognosis in pulmonology].

PMID- 11980134
TI  - [Domestic experience in minimally invasive myocardial revascularization].

PMID- 11980135
TI  - [Endotoxemia in children with chronic viral hepatitis B and methods of its
      reduction].

PMID- 11980136
TI  - [Calcium-phosphorus metabolism and bone metabolism in postmenopausal patients
      with the thyroid gland pathology].
AB  - Bone metabolism markers (bone alkaline phosphatase, ionized calcium, inorganic
      phosphorus, serum osteocalcin) and urinary excretion of hydroxyproline, Ca2+ and
      P after overnight fasting and of creatinine were studied in 52 female patients
      with endemic goiter and hypothyrosis (18 of these with decompensated
      hypothyrosis, 34 treated with thyroid hormones) and 48 women without thyroid
      diseases aged 45-60 years with menopause of no longer than 10 years (6.4 +/- 0.43
      years). Clinical and x-ray examinations were carried out in all women; hormonal
      status, basal serum levels of parathyroid hormone and calcitonin were evaluated.
      A trend to deceleration of bone remodeling was detected in the patients with
      untreated hypothyrosis in comparison with women without thyroid disease. Signs of
      increased bone resorption were detected in patients with endemic goiter and
      hypothyrosis receiving substitute hormone therapy; this gave grounds to refer
      patients of menopausal age with endemic goiter and hypothyrosis treated with oral
      thyroxin for a long time to a group at a high risk of osteoporosis and bone
      fractures and to start preventive osteotropic therapy from the first day of
      substitute thyroid hormone therapy.

PMID- 11980137
TI  - [Dependence of aspartate aminotransferase activity on enzyme concentration in the
      reaction mixture].

PMID- 11980138
TI  - [Liver monooxygenase system inducers in the treatment of respiratory distress
      syndrome in newborn].
AB  - Physical and biochemical parameters of pulmonary surfactant (PS) were studied in
      6-day-old rabbits with the respiratory distress syndrome (RDS) treated by
      benzonal and zixorin inductors. Surface-active characteristics of PS were
      impaired under conditions of RDS at the expense of deficiency of total
      phospholipids, specifically phosphatidylcholine (PC) and phosphatidylethanolamine
      (PEA). Treatment with benzonal and zixorin improved the surface-active
      characteristics of PS and increased the content of total phospholipids mainly at
      the expense of PC and PEA.

PMID- 11980139
TI  - [Use of a salivary alpha-amylase inhibitor in the saliva biochemical study].
AB  - Amylolytic activity of oral fluid, saliva, and serum is maintained by alpha
      amylases of different origin. Salivary and nonsalivary (mainly pancreatic)
      amylases can be recognized by reliable and simple in vitro tests with human
      salivary alpha-amylase inhibitor.

PMID- 11980140
TI  - [Platelet antigens (designation, structural molecular basis, incidence in
      population) (a literature review)].

PMID- 11980141
TI  - [Morphology of biological fluids in clinical laboratory diagnosis].

PMID- 11980142
TI  - [A new approach to differential diagnosis of benign and malignant pulmonary and
      mediastinal tumors].

PMID- 11980143
TI  - [Immunoenzyme analysis of natural antibodies to endogenous bioregulators in
      patients with systemic lupus erythematosus].
AB  - Serum levels of autoantibodies to endogenous bioregulators (prostaglandin F2
      alpha, angiotensin II, epinephrine, bovine serum albumin, dinitrophenol) were
      measured in patients with systemic and integumental lupus erythematosus and
      donors and the diagnostic significance of deviations of these levels from the
      norm was evaluated. A total of 75 patients with lupus erythematosus aged 19-54
      years with disease lasting for 0.5 to 18 months were examined. Significant
      differences between patients and donors were observed as regards virtually all
      parameters except IgG to angiotensin II.

PMID- 11980144
TI  - [Clinical and diagnostic significance of analysis of thyroid hormone in newborn].

PMID- 11980145
TI  - [Cytoplasmatic granularity of neutrophilic leukocytes (a literature review)].

PMID- 11980146
TI  - [Lymphoid tissue neoplasms: lympholeukemia and (or) lymphoma].

PMID- 11980147
TI  - [Prognosis of iron deficiency in women of reproductive age].
AB  - Time organization of erythropoiesis and iron metabolism was studied in women of
      reproductive age. The studies showed that a constant level of erythrocytes and
      hemoglobin in peripheral blood during the menstrual cycle is maintained due to
      different intensity of erythropoiesis and iron metabolism. Circadian rhythm of
      sideremia is characterized by the greatest amplitude of fluctuations during the
      early lutein phase of the cycle in all healthy women. The difference between
      serum iron concentrations in the morning and afternoon (8.00-14.00) and in the
      evening (21.00-24.00) is 4-8 mumol/liter. A lesser difference between the morning
      and evening concentration of the trace element during the early lutein phase
      indicates iron dysmetabolism and is prognostically unfavorable with regard to
      development of iron deficiency.

PMID- 11980148
TI  - [Recommendations of the American National Council for Clinical Laboratory
      Standardization (NCCLS)].

PMID- 11980149
TI  - [Use of column and thin layer chromatography for detection of vanillyl mandelic
      acid in urine].
AB  - The excretion of vanillylmandelic acid was measured by column chromatography of
      urinary samples on aluminum oxide with subsequent thin-layer chromatography on
      silica gel. Use of aluminum oxide allowed application of greater urine samples
      (up to 0.1% of 24-h diuresis) onto chromatographic plates and essentially
      improved the quality of separation of vanillylmandelic acid from other
      phenylcarbonic acids by thin-layer chromatography, as well as the specificity and
      reproducibility of measurements.

PMID- 11980150
TI  - [Glucophot BP-"M" analyzer for blood analysis].
AB  - Miniature analyzer Glucophot BP-"M", intended for express measurements of glucose
      concentrations in capillary blood, was tested under clinical conditions. The
      reference method was the hexokinase method for glucose measurements on a Spectrum
      11 biochemical analyzer (Abbott); in addition, glucose measurements were carried
      out on a One Touch-11 glucometer (Johnson-Johnson). The results evidence that the
      reproducibility and correctness of glucose analysis by the Glucophot BP-"M"
      analyzer both in health and disease met the requirements to laboratory
      measurements performed by "dry" chemical methods and demonstrated its high
      analytical reliability.

PMID- 11980151
TI  - [Current problems of viral and alcohol diseases of the liver].
AB  - 517 cases of acute viral hepatitis (AVH) and 1203 cases of hepatic cirrhosis (HC)
      have been analysed. In recent 20-28 year the trend to a decline in the role of
      HBV infection in the origin of both AVH and HC. The least lethality was reported
      for viral C-cirrhoses. When the sale of heavy drinks was limited by the law,
      lethality of alcoholic hepatic cirrhosis came down 2.5-fold. Among hepatic
      cirrhoses, the percentage of alcoholic forms has increased from 35.6% in 1972
      1984 to 41.5% in 1996-2000. The worst prognosis is now stated for alcoholic-viral
      and polyviral hepatic cirrhoses. The data for 4.5 years evidence for at least 50%
      lethality in this group.

PMID- 11980152
TI  - [Cardiac arrhythmia in cardiac embolism].
AB  - To study cardiac arrhythmia in patients with cardiocerebral embolism, we examined
      330 patients with ischemic stroke using ECG and Holter monitoring. 33 patients
      were control. Group 1 consisted of 104(31.5%) patients with cardioembolic stroke,
      group 2--of 226(68.5%) patients with other pathogenetic stroke subtypes. Number
      of patients with rare and frequent supra- and ventricular extrasystole in groups
      1 and 2 was not essentially different. Paroxysms of supra- and ventricular
      tachycardia, variants of sick sinus syndrome (SSS) and transitory
      atrioventricular block (AV block) of the second and third degree were identified
      with comparable frequency in groups 1 and 2 (0.9 to 5.8% patients). Paroxysmal
      atrial fibrillation (AF) was registered in 31.8% of group 1 patients and 15.9% of
      group 2 patients. Permanent AF occurred in 31.8 and 7.5% patients of groups 1 and
      2, respectively (p < 0.00001). Thus, cardiocerebral embolism is observed most
      frequently in paroxysmal and permanent forms of AF. Variants of extrasystole,
      paroxysmal supra- and ventricular tachycardia, SSS and AV-block are not
      associated with embolic complications.

PMID- 11980153
TI  - [Infectious endocarditis of the left heart atrium in injection drug addicts].
AB  - AIM: To study etiology, clinical picture, course and prognosis of left heart
      infection endocarditis (LHIE) in drug addicts. MATERIAL AND METHODS: 61 drug
      addicts entered the study. 14 of them had lesions of the left heart valves (group
      1), 11--of the right and left heart valves (group 2), 36--of the tricuspid valve
      (group 3), 39 control patients with LHIE had no addiction. Mean age in group 1
      was 25.9 +/- 8.8 years, in group 4--48.3 +/- 12.6 years, p < 0.001. RESULTS:
      Females prevailed in group 3, males--in group 4. Splenomegaly was more frequent
      in the addicts. Lung lesions (abscesses and infarction) prevailed in groups 2 and
      3. Cardiac failure was found more frequently in groups 1 and 4, edema--in group
      3, brain affections--in groups 1 and 4. Renal damage was encountered with equal
      frequency in the addicts and non-addicts. The addicts had, largely, infarctions,
      non-addicts--glomerulonephritis. Viral hepatitis C was associated with drug
      addiction. Blood seedings were on the whole positive in 54%, in drug addicts--in
      69%. St. aureus predominated (44%). In group 3 it was detected in 72%. It was
      higher than in groups 4 and 1 (p < 0.001, p < 0.01, respectively). Lethality in
      group 1 (57%) was higher than in group 3 (22%, p < 0.05) and group 2 (18%, p <
      0.01). The leading cause of death in group 1 was cerebral thromboembolism with
      development of meningoencephalitis. Other causes--progressive cardiac and renal
      failure.

PMID- 11980154
TI  - [Combination of Libman-Sacks endocarditis with infectious endocarditis].
AB  - Out of 242 patients treated for systemic lupus erythematosus (SLE) in Novosibirsk
      for 15 years, valvular lesions and endocarditis were diagnosed in 41(16.9%)
      patients. Combination of Libman-Sax endocarditis (LSE) with infectious
      endocarditis (IE) was observed in three patients (two women, one man, age 18-40
      year). SLE ran a subacute course in one woman, an acute one--in the other. LSE
      emerged early in SLE in two patients. All the patients had polyorganic lupus
      pathology, lupus nephritis with nephrotic syndrome (morphological class IV). Two
      patients had mitral valve disease, one patient--mitral-aortic disease. The rise
      of secondary IE was seen after massive immunosuppressive therapy. The diagnosis
      of secondary IE was made after SLE duration for 10-36 months. At IE diagnosis,
      all the patients had high titers of blood antiphospholipid antibodies. IE was of
      staphylococcal origin in two patients and candidosis-induced in one patient. In
      SLE with IE there was thromboembolic syndrome. LSE and IE have related aspects
      which should be regarded in clinical practice: possible "IE mask" in LSE, risk of
      secondary IE in about 10% of LSE patients, prophylactic measures necessary to
      prevent IE in hemodynamically prominent forms of LSE.

PMID- 11980155
TI  - [Pathogenesis of "Leningrad" (blockade) hypertension (60-th anniversary of the
      Leningrad blockade)].
AB  - Leningrad (blockade) hypertension observed in survivors of the Leningrad blockade
      during the World War II is a unique form of hypertension initiated and maintained
      pathogenetically by disturbed neuroregulation resultant from a severe
      psychoemotional stress. Pathogenesis of Leningrad hypertension involves
      mechanisms playing a key role in pathogenesis of other forms of essential
      hypertension. A characteristic feature of this pathogenesis is interaction of the
      initial and key neurogenic factor with such hypertensive factors of alimentary
      dystrophic genesis as lesions of the vascular wall secondary to marked
      hypoproteinemia and hypovolemia. Later, in addition to hypertension the patients
      developed atherosclerosis, nephrosclerosis and other diseases.

PMID- 11980156
TI  - [Clinico-immunological and bronchological characteristics of the late onset
      asthma].
AB  - Clinicoimmunological and bronchological examination was performed in 452 patients
      with bronchial asthma (BA) which were divided into two groups: 286 patients with
      late BA (onset at the age of 40 and older) and 166 patients with BA onset at the
      age under 40. Late BA develops because of non-allergic factors, especially
      persistent bronchopulmonary infection. Bad pulmonary background contributes to
      development of rapidly progressing respiratory obstruction with irreversible
      component. Cytological tests of the bronchoalveolar lavage revealed subnormal
      cytosis and viability of the cells, high counts of eosinophils and neutrophils,
      cells of bronchial epithelium with signs of dystrophy, low count of alveolar
      macrophages. Immunological tests in late BA patients evidence for suppression of
      local bronchopulmonary defense, low levels of both T-helper and T-suppressor
      cells, deficiency of C3 and C4, high serum IgG. The above changes are determined
      for the most part by immunosuppression induced by concomitant and past
      respiratory diseases.

PMID- 11980157
TI  - [Clinical and pathogenetic features of bronchial asthma in patients with
      concomitant Bauhin's valve failure].
AB  - Combination of bronchial asthma (BA) with Bauhin's valve failure (BVF) is
      characterized by exogenic form of BA, extrapulmonary allergy, digestion problems.
      Examination of 36 such patients using endoscopy, manometry and tube duodenography
      has shown frequent chronic disorder of duodenal patency and gastroesophageal
      reflux, dysbacteriosis of the large and small intestines. High concentration of
      middle mass molecular peptides reflects endogenic intoxication associated with
      abnormal composition of intestinal microflora. The above alterations give grounds
      to consider BVF as a factor of BA pathogenesis.

PMID- 11980158
TI  - [Types of structural-functional disorders in severe chronic obstructive pulmonary
      disease].
AB  - To differentiate approaches to assessment of treatment and prognosis
      specificities in a severe course of chronic obstructive pulmonary diseases
      (COPD), a study was made of 30 patients with long-term COPD. The patients were
      divided into groups by the severity of respiratory insufficiency which was
      investigated by saturation of 0(2) and gas composition of arterialized capillary
      blood, flow-volume curve and bodyplethysmography, ECG, echo-CG. High resolution
      computed tomography of the lungs was used to evaluate diffuse changes of
      pulmonary tissue and its morphological rearrangement. Basing on the
      rhoentgenomorphological picture, most typical variants of pulmonary tissue
      changes were identified. Comparison with the clinical and laboratory-instrumental
      data allowed to characterize four structural-functional types which occur in
      severe COPD. Etiological and pathogenetic features of the above types (the role
      of smoking, in particular) and their contribution to development of pulmonary
      hypertension, treatment and prognosis are discussed.

PMID- 11980159
TI  - [Magnetic load in pneumonia patients].
AB  - The change of bronchial permeability under magnetic load has been investigated in
      122 patients with pneumonia 18 to 60 years of age. Two variants of bronchial
      reaction and a correlation between the time to onset, severity of the reaction
      and bronchial inflammation have been found. Magnetic load proved able to reveal
      high magnetic sensitivity of the organism. Peculiarities of pneumonia clinical
      course and outcome in patients with high magnetic sensitivity show the necessity
      of additional medical and prophylactic measures.

PMID- 11980160
TI  - [Chronotherapy approaches in the treatment of gastroduodenal ulcer].
AB  - Each patient with ulcer has his/her own 24-h biorhythm of acid production,
      features of food alkalization, duration of duodenogastric and gastroesophageal
      reflux. Pharmacological test conducted in prolonged 24-h pH-metry helps to select
      the most effective antisecretory drug, while analysis of 24-h biorhythm of acid
      production--optimal time for drug intake and number of its daily doses.

PMID- 11980161
TI  - [Course of chronic hepatitis B and C and constitutional characteristics of the
      patients].
AB  - The relationship between hepatitis course and constitution assessed by the signs
      of 3 major diatheses (dyscrasic--DD. arthritic--AD and psoriatic--PD) was studied
      in 41 patients with HBV infection (low active-25 patients, moderate activity-6
      patients, cirrhosis-10 patients) and 62 patients with NCV infection (low active
      23, moderate-13, cirrhosis-26). In both infections domination of DD over AD and
      PD was associated with more severe course of the disease while Ad domination over
      DD and PD indicated a mild course. It is suggested that constitutional
      characteristics should be taken in consideration when assessing the course and
      prognosis of HBV- and HCV-infection.

PMID- 11980162
TI  - [Autonomic system disorders in endemic goiter].
AB  - Vegetative tonicity, reactivity and provision were studied in 88 patients with
      endemic goiter (EG) aged 18 to 40 years. Vegetative dystonia syndrome (VDS) in EG
      develops as parasympathicotonia. Subjective symptoms of vegetative dysregulation
      are more pronounced in high reactive and personality anxiety, in neurotism, they
      do not depend on extra- or introversion. VDS in EG deteriorates mental and
      physical performance, attention. Vegetative reactivity in EG becomes
      hypersympathicotonic. Vegetative dystonia affects reaction to the disease.
      Prolapse of heart valves often seen in EG patients results rather from
      hypothyroid edema of the myocardium than from VDS. Therefore, treatment of such
      patients with beta-adrenoblockers is not grounded. Vegetative dysregulation
      gradually attenuates in response to replacement hormone therapy with thyroxine.

PMID- 11980163
TI  - [A comparative study of anapriline and carvedilol effectiveness in patients with
      thyrotoxicosis in pre- and postoperative periods].
AB  - Thyrotoxicosis often affects cardiovascular system. Structural-functional
      condition of the myocardium is essential in the outcome of surgical intervention
      on the thyroid in thyrotoxicosis and indicates effectiveness of the treatment. A
      comparative trial studied the effects of beta-blockers (anaprilin and carvedilol)
      on preoperative condition of left-ventricular (LV) myocardium and late after
      subtotal resection of the thyroid gland. 27 thyrotoxicosis patients with
      myocardial remodeling in the form of concentric LV hypertrophy entered the trial.
      Though in preoperative preparation anapriline is recommended, in postoperative
      period it is better to use carvedilol as it has a good effect on reverse
      development of myocardial remodeling and hemodynamics in view of its balanced
      beta- and alpha-adrenoblocking action.

PMID- 11980164
TI  - [Assessment of time-dependent effects of long-acting altiazem in patients with
      hypertension stage II].
AB  - A chronodiagnostic examination covered 27 patients with hypertension stage II of
      indifferent chronotype. The patients were divided into 3 groups by the time of
      intake of a single daily dose of altiazem--at 8 a.m., 14 p.m., 20 p.m.
      Chronological organization of the cardiovascular system was studied with
      autorhythmometry for 3 days in 4-h intervals including night before and in the
      end of the treatment. Echo-CG, doppler echocardiography and rheoencephalography
      investigated hemodynamics once daily also before and in the end of the treatment.
      The findings show advantage of chronotherapeutic prescription of altiazem PP in a
      mean dose 220 mg/day at evening hours in non-chronodependent patients with
      hypertension stage II because such a regimen brought about more adequate
      restoration of the cardiovascular system time organization both by the spectrum
      of significant rhythms and their parameters; by better improvement of left
      ventricular diastolic function and pulse cerebral flow. Faster achievement of the
      therapeutic effect in the evening intake of altiazem supports its
      chronotherapeutic administration. This leads to reduction of the drug course dose
      and, therefore, treatment duration.

PMID- 11980165
TI  - [Effects of long-term therapy with losartan on baroreflex regulation of
      cardiovascular system].
AB  - To assess dynamics of structural-functional parameters of the circulatory system
      including the state of the cardiopulmonary baroreflex (CPBR) in patients with
      ischemic heart disease (IHD) and cardiac failure (CF) on losartan treatment, we
      studied 14 IHD men with CF (NYHA functional class II-III), mean age 54.6 +/- 7.1
      years. Before and after losartan treatment the patients were examined using
      echocardiography, radiocardiography with 131-I albumin, occlusion
      plethysmography, 131-I hippuran clearance. CPBP was estimated by the change in
      circulation flow rate in the forearm in low body rarefaction by means of low
      pressure camera. Losartan was given in maximal tolerance dose (25-100 mg/day).
      Examination in the end of the treatment demonstrated diminished venous tone,
      increased blood flow in the forearm, reduced volume of circulating plasm,
      elevated hematocrit, higher ratio of early to late filling peaks of the left
      ventricle, progression of baroreflex dysfunction. Thus, long-term losartan
      treatment promoted improvement in peripheral vascular tonicity, diastolic
      function of left-ventricular myocardium, reduction in circulating plasm volume,
      progression of baroreflex dysfunction.

PMID- 11980166
TI  - [Difficulties in diagnosis of infarction of the right ventricular myocardium].
AB  - About half of the patients with symptoms of inferior acute myocardial infarction
      (MI) of the left ventricle (LV) are found to have proximal occlusion of the
      dominant right coronary artery presented on ECG by ischemia or infarction of the
      right ventricular wall. Hypotension, high pressure in the jugular veins and, in
      some cases, shock with clear lung fields--typical clinical picture of right
      ventricular MI. The diagnosis begins with ECG picture of LV lower wall ischemia
      (rise of ST wave in leads II, III and aVF) with possible emergence of a
      pathological wave Q and right ventricular ischemia (rise of ST wave in leads V3R
      V6R and its depression in leads V2-V4). Echo-CG and balanced
      radioventriculography were used for verification of the diagnosis, precise
      localization of the myocardial lesion. Therapy of patients with right ventricular
      MI consists in maintenance of adequite preload of the right ventricle, inotropic
      support and control over atrioventricular conduction.

PMID- 11980167
TI  - [Diagnosis and treatment of gastrin-producing pancreatic tumors].
AB  - Current literature data on the clinical course, diagnosis and treatment of
      gastrinoma, one of the most frequent neuroendocrine tumors of the thyroid, as
      well as 23 cases with Zollinger-Ellison syndrome treated by the authors are
      analysed in detail. Peculiarities of the clinical course, difficulties of
      syndrome diagnosis, principles of updated topical diagnosis of gastrinoma,
      conservative and surgical treatments including treatment of multiple endocrine
      neoplasia syndrome are described.

PMID- 11980168
TI  - Pharmaceutical care research: hard or soft?--Part II.
AB  - In pharmaceutical care research (PCR) quantitative research methodologies are
      strongly represented. However, in PCR also other qualities should be included in
      the tool kit of the researcher. For that purpose, it is argued that social
      science provides rich frameworks applicable for PCR. It offers both quantitative
      and qualitative methodological frameworks. In the most challenging and powerful
      field work the two approaches are combined. The case study design is a framework
      to synthesise quantitative and qualitative research approaches. For the
      development of PCR the case study design may be an important addition to the tool
      kit of its researchers.

PMID- 11980169
TI  - Analysis and quantification of prescribing and transcription errors in a
      paediatric oncology service.
AB  - OBJECTIVE: To analyse and quantify the omission errors linked to physicians'
      prescribing and errors linked to nurses' transcription and to identify the type
      and frequency of factors associated. No pharmacological factors are taken into
      account. DESIGN: Analysis of physicians' prescriptions and nurses' transcriptions
      in chemotherapeutic treatments (20 patient files) and non-chemotherapeutic
      treatments (20 patient files); retrospective study. SETTING: Paediatric onco
      haematology unit. MAIN OUTCOME MEASURES: Categorisation of physicians'
      prescriptions as complete or incomplete, categorisation of the various nurses'
      transcriptions as correct or incorrect. RESULTS: Physicians' prescriptions were
      complete for 61.6% of non-chemotherapy treatments. As each prescription is
      transcribed twice, two nurses' transcription sheets are filled in by the nurses.
      At the first transcription 79.3% of non-chemotherapy prescriptions and 88.2% of
      chemotherapy prescriptions were transcribed correctly, while in the second sheet
      these percentages were respectively 96.2% and 93.7%. CONCLUSIONS: Too many sheets
      of paper generate confusion and increase the risk of errors. The several
      transcriptions are, in both types of treatment, sources of errors. The problems
      identified in this study allowed us to open a discussion as how to improve the
      physicians prescriptions and the nurses' transcription sheets.

PMID- 11980170
TI  - Recommended structure for reporting economic evaluation on pharmaceuticals in
      Belgium.
AB  - Pharmaco-economic evaluations become more important for the reimbursement of
      pharmaceuticals, and will be obligatory for new pharmaceutical drugs for which an
      added therapeutic value is claimed and a price premium is proposed by the
      manufacturer. Therefore, it is important to guide purchasers and providers of
      pharmaceutical care in their efforts related to the evaluation process. Standard
      Report Format can support the quality, transparency and exhaustiveness of the
      data submitted. A multidisciplinary task force developed a Standard Report Format
      for pharmaco-economic evaluations in Belgium.

PMID- 11980171
TI  - Cost-effectiveness of periconceptional supplementation of folic acid.
AB  - BACKGROUND: Supplementation of folic acid prior to and in the beginning of
      pregnancy may prevent neural tube defects (NTDs) in newborns--such as spina
      bifida--and possibly other congenital malformations. OBJECTIVE: To estimate cost
      effectiveness of periconceptional supplementation of folic acid using pharmaco
      economic model calculation. METHOD: Probabilities for NTDs, risk reductions
      through periconceptional supplementation of folic acid and lifetime costs of care
      for children with spina bifida were estimated using Dutch registrations and
      international literature. MAIN OUTCOME MEASURE: Cost effectiveness was expressed
      in net costs per discounted life-year gained. Cost effectiveness was calculated
      in the baseline and in sensitivity analysis. RESULTS: Estimated cost
      effectiveness of periconceptional supplementation of folic acid amounts to NLG
      3900 ([symbol: see text] 1800) in the base case. In sensitivity analysis cost
      effectiveness mostly remains below NLG 10,000 ([symbol: see text] 4500).
      CONCLUSION: Periconceptional supplementation of folic acid shows a favorable cost
      effectiveness. From pharmaco-economic point of view this justifies further
      stimulation of folic-acid supplementation prior to pregnancy. This can be done
      through targeted education by health-care workers, such as pharmacists.

PMID- 11980172
TI  - What are African monarchs (Aves, Passeriformes)? A phylogenetic analysis of
      mitochondrial genes.
AB  - We address the phylogenetic relationships of ten passerine bird species
      representing the five presently supposed monarchine (family Monarchidae) genera
      (Terpsiphone, Hypothymis, Elminia, Trochocercus, Erythrocercus) from Asia and
      Africa, as well as three monarchs from Australasia, three representatives of the
      related genera Rhipidura and Dicrurus, and 20 representatives of 11 other oscine
      groups (including two Culicicapa flycatchers) and one sub-oscine, using two
      partial mitochondrial genes (cytochrome b and large sub-unit ribosomal 16S RNA).
      Molecular data corroborate ecological, ethological and morphological observations
      on the probable heterogeneity of Trochocercus and indicate that this genus is
      polyphyletic; two of its species are members of Monarchidae allied to Terpsiphone
      and Hypothymis; the others are more closely related to Elminia. Elminia is not a
      member of Monarchidae and is not related to any other sampled species, except
      Culicicapa. Erythrocercus is also outside the Monarchidae but inside a Sylvii
      Pycnonotidae group. These results point once more to the need of a fully revised
      phylogeny of passerine birds.

PMID- 11980173
TI  - Early steps of metabolism evolution inferred by cladistic analysis of amino acid
      catabolic pathways.
AB  - Among abiotic molecules available in primitive environments, free amino acids are
      good candidates as the first source of energy and molecules for early protocells.
      Amino acid catabolic pathways are likely to be one of the very first metabolic
      pathways of life. Among them, which ones were the first to emerge? A cladistic
      analysis of catabolic pathways of the sixteen aliphatic amino acids and two
      portions of the Krebs cycle is performed using four criteria of homology. The
      cladogram shows that the earliest pathways to emerge are not portions of the
      Krebs cycle but catabolisms of aspartate, asparagine, glutamate, glutamine,
      proline, arginine. Earliest enzymatic catabolic functions were deaminations and
      transaminations. Later on appeared enzymatic decarboxylations. The consensus tree
      allows to propose four time spans for catabolism development and corroborates the
      views of Cordon in 1990 about the evolution of catabolism.

PMID- 11980174
TI  - Coding of insertion-deletion events of the chloroplastic intergene atp beta-rbcL
      for the phylogeny of the Valerianeae tribe (Valerianaceae).
AB  - A preliminary analysis of the sequence alignment of the chloroplast intergene atp
      beta-rbcL in tribe Valerianeae reveals that insertion-deletion evolutionary
      events ('indels'), combined with nucleotide substitutions, have occurred in large
      zones in some of the studied taxa. Due to the frequent occurrence and large size
      of indels within this tribe, intergene length varies from 531 to 788 base pairs
      within the studied species. This situation poses gap coding problems that we had
      to tackle before phylogenetic analysis. Four methods of gap coding were used:
      elimination of gapped sites ('complete omission'), 'missing data', 'fifth base'
      and Barriel's coding method, which translates indels into new multistate
      characters in the data matrix. After application of these four methods of data
      treatment, phylogenetic analyses (maximum parsimony) did not lead to very
      different results. Three robust clades emerged in each case, corresponding to the
      Centranthinae subtribe (genus Centranthus), the Fediinae subtribe (genera Fedia
      and Valerianella), and the American species of Valeriana. The theoretical basis
      and biological significance of these four methods are discussed in order to apply
      the best ones in future studies.

PMID- 11980175
TI  - Molecular phylogeny of French Guiana Hylinae: implications for the systematic and
      biodiversity of the Neotropical frogs.
AB  - In this study we used nucleotide sequences from a segment of mitochondrial 16S
      ribosomal DNA gene to investigate the evolutionary relationships of some French
      Guiana Hylinae. New sequences, representing the members of different French
      Guiana frogs-five specimens of the Scinax genus, two Hyla, one Osteocephalus, one
      Hyalinobatrachium and two Rana as out-group-were examined. In addition, 26
      sequences available from GenBank database representing the other subfamilies of
      the Hylidae were added to our study. This work allowed us to clarify
      relationships within the four hylids subfamilies (Pelodryadinae, Phyllomedusinae,
      Hemiphractinae and Hylinae) and the phylogenetic placement of the enigmatic
      Scinax genus within the Hylidae. We found that: (1) the Scinax genus displays a
      high level of differentiation in comparison to two other genera (Litoria and
      Hyla) belonging to 'Hylidae' family; (2) the Hylinae are paraphyletic given the
      position of the Litoria, which was the sister-group of the Hyla and the
      Osteocephalus genera; (3) the anterior works and our results (based on two
      different data sets) showed the paraphyly of the Hylidae questioning the validity
      of this family; (4) the reassessment of these different taxonomic groups will
      induce a huge implication on the estimation (past, present and future) of the
      biodiversity (in Neotropical frogs).

PMID- 11980176
TI  - [Selectivity and environmental variations in herbivory by Orthoptera].
AB  - The aim of this study is 1 degree) to quantify environmental changes in herbivory
      due to Orthoptera on two perennial grasses and 2 degrees) to assess the processes
      involved in the control of herbivory. Herbivory varies strongly according to
      shade, drought and mowing, and is positively related to vapour pressure deficit
      and temperature. Besides the hypothesis of a trophic control of herbivory, our
      results are consistent with a microclimatic control of herbivory by Orthoptera.
      The coexistence of different hypothesis of herbivory control may depend on the
      studied system and specifically on the type of herbivore involved.

PMID- 11980177
TI  - Global Positioning System (GPS) location accuracy improvement due to selective
      availability removal.
AB  - Global Positioning System (GPS) is an important new technology for spatio
      temporal behaviour studies of animals. Differential correction improves location
      accuracy. Previously, it mostly removed partially the influence of Selective
      Availability (SA). SA was deactivated in May 2000. The aim of this study was to
      quantify the influence of SA cancellation on location accuracy of various GPS
      receivers. We tested the accuracy of locations obtained from non-differential and
      differential GPS animal collars before and after SA removal. We found a
      significant improvement in accuracy for both types of GPS collars. However,
      differential GPS still provides more accurate locations.

PMID- 11980178
TI  - Copepod feeding in a tuna fishery area of the tropical Atlantic Ocean.
AB  - Biomass, feeding and metabolic rates of planktonic copepods were studied in an
      oligotrophic area of the tropical Atlantic Ocean during an instability wave
      period (boreal summer) and a stratified period (boreal winter). In summer,
      zooplankton biomass was higher than in winter, showing a positive effect of the
      instability wave. Moreover, feeding equilibrated metabolic expenditures of
      copepods in most cases during the instability. In contrast, in stratified
      conditions copepods did not equilibrate their metabolic budget. Our results
      suggest that the microbial loop was the dominant trophic pathway during both
      periods but with a quicker cycling during the instability.

PMID- 11980179
TI  - Embryonic expression of the leptin receptor gene in mesoderm-derived tissues.
AB  - Leptin acts on the hypothalamus to reduce food intake and on a number of non
      neuronal tissues via specific receptors (Lepr). The use of in situ hybridisation
      to map the Lepr gene in pre-natal mice revealed transcripts in the yolk sac in
      various structures of the central nervous system and in mesoderm-derived tissues,
      such as cartilage/bone primordia and musculoaponeurotic laminae. At later stages,
      significant amounts of Lepr were expressed in the region surrounding the
      developing eye of the embryo. Lepr was also found to be expressed in the choroid,
      sclera and connective tissues of the limbus in the adult eye. In conclusion, we
      have identified new targets for leptin action during embryogenesis and adulthood.

PMID- 11980180
TI  - [Natural hybridization between 2 sympatric species of mice, Mus musculus
      domesticus L. and Mus spretus Lataste].
AB  - Using protein loci and DNA markers, we show by a multilocus genetic analysis that
      certain populations of the two sympatric mouse species Mus musculus domesticus
      and Mus spretus show clear signs of partial introgression. Given the sterility of
      F1 males and the known partial genetic incompatibilities between the genomes of
      the two species, our finding does not invalidate the biological species complex,
      but allows to think that very limited genetic exchanges remain possible even long
      after the divergence of taxa. This may have some consequences on the dynamics of
      certain kinds of invasive or advantageous DNAs like transposable elements or
      pathogen resistance genes.

PMID- 11980181
TI  - [Isotopic composition of the delta-18O--delta-13C from the otoliths of reef fish
      from Taiaro (Tuamotu, French Polynesia): isotopic and biological implications].
AB  - Nuclei (larval stage) and outer parts (adult stage) of fish otoliths from the
      Taiaro closed lagoon (French Polynesia) and adjacent ocean have been analysed for
      the C-O isotopic compositions. delta 18O values of the nuclei of both populations
      indicate that isotopic equilibrium is reached. This implies that the lagoonal
      fish population has done its complete biological cycle in the lagoon and
      represents an adaptation in a closed system. delta 18O values of the outer parts
      show a slight isotopic disequilibrium (< 0.2@1000) interpreted in term of vital
      effect. All the delta 13C values exhibit a strong isotopic disequilibrium related
      to metabolic activity.

PMID- 11980182
TI  - Nutritional regulators of the hypothalamic-pituitary axis in pigs.
AB  - Nutritional signals are detected by the central nervous system (CNS) and
      translated by the neuroendocrine system into signals that alter secretion of LH
      and growth hormone (GH). Furthermore, these signals directly affect the activity
      of the pituitary gland independently of CNS input. Insulin-like growth factor I
      (IGF-I), insulin, leptin and specific metabolites, such as glucose and free fatty
      acids (FFA), are potential signals of the metabolic status to the brain-pituitary
      axis. Intravenous injection of a lipid emulsion or glucose suppressed the GH and
      LH response to GH releasing hormone (GHRH) and GnRH, respectively. Insulin and
      IGF-I regulation of LH and GH secretion occur at the pituitary gland. Feed
      deprivation for 24 h suppressed leptin secretion without affecting LH or GH
      secretion, whereas central administration of leptin resulted in a decrease in
      feed intake and an increase in GH secretion. Oestrogen-induced leptin gene
      expression in adipose tissue increased with age and adiposity in pigs. Leptin
      stimulated GnRH release from hypothalamic tissue in vitro. These results identify
      putative signals that link metabolic status and neuroendocrine control of growth
      and reproduction by altering endocrine function during periods of fasting, feed
      restriction and lactation.

PMID- 11980183
TI  - Basic mechanisms of fertilization and parthenogenesis in pigs.
AB  - Fertilization of the egg, or oocyte, initiates the entire developmental process,
      but while the mechanism by which the spermatozoa triggers the oocyte to resume
      meiosis has been studied extensively, conclusions about this process are still
      elusive. Some workers have suggested that a molecule on the surface of the
      spermatozoon may interact with a receptor on the plasma membrane of the oocyte,
      thereby triggering the oocyte to resume meiosis. Other workers have focused on a
      factor or factors located in the cytoplasm of the spermatozoa that is deposited
      into the cytoplasm of the oocyte. A hallmark response to fertilization in mammals
      is an increase in the cytoplasmic concentration of free Ca2+ in the oocyte. Many
      additional studies have focused on treatments that will induce the oocyte to
      resume meiosis without being fertilized. The process of resumption of meiosis
      without a spermatozoon is generally referred to as activation or parthenogenesis.
      Activation of the oocyte is very important for a number of oocyte- or embryo
      related technologies including intracytoplasmic sperm injection (ICSI) and
      cloning by nuclear transfer. This review will focus on what is known about
      fertilization and methods to mimic this process, with an emphasis on pigs.

PMID- 11980184
TI  - Phagocytosis of boar spermatozoa in vitro and in vivo.
AB  - For successful conception, fertilization-competent spermatozoa must be present at
      the site of fertilization in adequate numbers until ovulation has taken place. In
      pigs, a large volume of semen is delivered into the uterus. Most, if not all, of
      the inseminated liquid is voided from the vulva within a few hours after
      insemination and approximately 45% of the spermatozoa are lost. Large numbers of
      spermatozoa are also lost due to phagocytosis by polymorphonuclear leukocytes
      (PMNs). In pigs, the recruitment of PMNs to the uterine lumen appears to be
      triggered by insemination of a volume of liquid, rather than by specific
      components of that liquid or by spermatozoa or seminal plasma. However,
      persistence of large numbers of PMNs in the uterine lumen at > 12 h after
      insemination appears to depend on the presence of spermatozoa in the inseminate.
      In vitro studies have indicated that damaged, killed or capacitated spermatozoa
      are not phagocytosed preferentially, but that capacitation treatment strongly
      reduced phagocytosis of spermatozoa. Recent studies have also shown that PMN
      recruitment and phagocytosis of spermatozoa in vivo can be reduced by addition of
      caffeine plus CaCl2 to the inseminate, which appeared to have positive
      consequences for the longer term availability of spermatozoa at the site of
      fertilization.

PMID- 11980185
TI  - Involvement of oviduct in sperm capacitation and oocyte development in pigs.
AB  - An overview is presented on the structure and function of the pig oviduct in
      relation to sperm capacitation and oocyte development in vivo. In pigs, a
      functional sperm reservoir is established in the uterotubal junction-isthmus when
      sperm deposition occurs before ovulation. Capacitation is assumed to occur in
      this location, and spermatozoa progress towards the ampullary-isthmic junction at
      about the time of ovulation as a consequence of capacitation and hyperactivation.
      Preliminary data from our laboratory on viable spermatozoa retrieved from the
      sperm reservoir and the ampullary-isthmic junction of mated sows at pre- and
      periovulation oestrus showed that the largest subpopulation (60-90%) was of
      uncapacitated spermatozoa (using merocyanine-540), whereas 6-37% of the gated
      cells were capacitated spermatozoa. Incubation in a capacitation-inducing medium
      (bicarbonate-containing modified Brackett-Oliphant medium; mBO) for < 30 min
      effected capacitation readily, more markedly in ampullary-isthmic junction
      samples than in samples from the uterotubal junction, thereby indicating that
      uncapacitated spermatozoa responded to the addition of the effector bicarbonate
      at concentrations similar to those recorded in the periovulatory ampullary
      isthmic junction in vivo. Addition of preovulatory isthmic oviductal fluid and
      hyaluronan under a similar incubation regimen maintained tubal sperm viability
      without obvious induction of capacitation. This finding indicates that, before
      ovulation, the intraluminal fluid of the sperm reservoir might delay sperm
      capacitation, perhaps because of its hyaluronan content. Evidence is presented
      that the sperm population in the oviduct undergoes capacitation under particular
      conditions in the upper tubal compartments. The diverse response of spermatozoa
      to capacitation stimuli helps to ensure full rates of fertilization in vivo. Data
      are also provided on the importance of final zona pellucida maturation in the pig
      oviduct to warrant proper zona pellucida reaction after sperm penetration, which
      would address in part the abnormal occurrence of polyspermy in in vitro
      fertilization of pigs.

PMID- 11980186
TI  - Gamete adhesion molecules.
AB  - Despite the importance of fertilization for animal production, species
      preservation and controlling reproduction, the molecular basis underlying
      fertilization is not well understood. More progress has been made in mice than in
      other mammals, but targeted deletion of specific genes in the mouse has often
      yielded unexpected results. The pig is also a useful animal to study, as large
      numbers of pig gametes can be acquired easily. However, it appears that the pig
      zona pellucida proteins that bind to spermatozoa may not be homologues of ZP3,
      the mouse zona pellucida protein that spermatozoa bind to. Therefore, a zona
      pellucida receptor on spermatozoa that is important for mouse fertilization may
      be redundant, along with other receptors, in pig fertilization. In this review,
      the important steps of fertilization in pigs are discussed and the binding of pig
      gametes is compared with that of mouse gametes. In addition, the molecules that
      may be important for gamete adhesion are considered. New technical advances and
      creative ideas offer the opportunity to make important advances in this crucial
      area.

PMID- 11980187
TI  - In vitro fertilization and embryo development in pigs.
AB  - Considerable progress has been made in the in vitro production of pig embryos
      using improved methods for in vitro maturation (IVM) and fertilization (IVF).
      Despite the progress, polyspermic penetration remains a problem for in vitro
      matured oocytes. Variation among boars, ejaculates and IVF protocols used in
      different laboratories appears to influence the incidence of polyspermy. Recent
      studies indicate that oviduct cells and their secretions play a role in reducing
      polyspermy. Very early attempts to culture in vivo-derived pig embryos met with
      little success and most were arrested at the four-cell stage. At present, many
      culture media are available that can overcome the four-cell block and support
      development to the blastocyst stage. In contrast, blastocyst development of in
      vitro-produced (IVP) embryos in these culture media varies significantly.
      Significant differences in morphology and numbers of cells have been observed in
      in vitro-produced blastocysts compared with in vivo-derived blastocysts. Surgical
      transfer of in vitro-produced embryos to recipient animals has resulted in
      acceptable pregnancy rates with moderate litter sizes. Although several systems
      are available for the generation of in vitro-produced embryos, the problems of
      polyspermy and poor embryo survival prevent large-scale production of embryos.
      Further research should be directed to improve oocyte and embryo quality, and to
      develop methods to minimize polyspermy through development of better IVM, IVF and
      embryo culture techniques.

PMID- 11980188
TI  - Apoptosis during folliculogenesis in pigs.
AB  - The number of female germ cells in pig fetuses decreases by 70% between day 50
      after mating and day 300 after birth. Approximately 55% of antral follicles
      undergo degeneration (atresia) except during the 3 days before oestrus, when only
      15% of the follicles survive to ovulate. Apoptosis, a form of programmed cell
      death, is recognized as the mechanism of germ cell death and follicle atresia at
      all stages of folliculogenesis. The internucleosomal cleavage of genomic DNA
      caused by caspase-induced deoxyribonuclease activity was measured in pig
      granulosa cells by DNA fluorescence flow cytometry, densitometry of fluorescently
      labelled internucleosomal DNA fragments and immunohistochemical analysis of the
      3' end labelling of deoxyribonuclease-nicked DNA on frozen tissue sections.
      Follicular atresia during the 3 days before oestrus is associated with a 60-70%
      decrease in the secretion of FSH. In granulosa cells, apoptosis is associated
      with decreased cell proliferation and reduced production of oestradiol and
      inhibin. In cultured pig granulosa cells, FSH and IGF-I are anti-apoptotic and a
      caspase inhibitor blocked apoptosis, thereby providing evidence of caspase
      activity. Oocytes in most follicles have resumed meiotic maturation; therefore,
      one role for apoptosis and follicle atresia may be to act as a barrier to
      ovulation of oocytes that have not remained in meiotic arrest.

PMID- 11980189
TI  - Gene expression during pre- and peri-implantation embryonic development in pigs.
AB  - Embryo technological procedures such as in vitro production and cloning by
      nuclear transfer are not as advanced in pigs as in cattle and cannot yet be
      applied under field conditions. The present paper focuses on genome activation in
      in vivo-derived, in vitro-produced and nuclear transfer pig embryos with special
      emphasis on the development of embryonic nucleoli, where the ribosomal RNA (rRNA)
      genes transcribed can be used as markers for genome activity. In addition,
      contemporary data on gene expression in in vivo-derived pig embryos are reviewed.
      In in vivo-derived pig embryos, pronounced transcription is initiated at the four
      cell stage (the third cell cycle after fertilization), when nucleoli develop. In
      parallel with the development of the nucleoli as a result of rRNA gene
      activation, a cascade of other genes is also likely to be transcribed. However,
      apart from identification of transcripts for the oestrogen receptor at the
      blastocyst stage, reports on mRNAs resulting from initial transcription of the
      pig embryonic genome are lacking, in contrast to the situation in cattle and, in
      particular, mice. More information is available on gene expression during
      elongation of pig conceptuses, when the genes for steroidogenic enzymes,
      extracellular matrix receptors, oestrogen receptors, growth factors and their
      receptors, as well as retinol binding protein and retinoic acid receptors, are
      expressed. Nucleolus development appears to be disturbed in in vitro-produced pig
      embryos and in pig embryos reconstructed by nuclear transfer of granulosa cells
      to enucleated metaphase II oocytes produced by oocyte maturation in vivo or in
      vitro, which is indicative of disturbances in activation of rRNA genes.

PMID- 11980190
TI  - Functional analysis of autocrine and paracrine signalling at the uterine
      conceptus interface in pigs.
AB  - The complexity of implantation necessitates intimate dialogue between conceptus
      and maternal cells, and precise coordination of maternal and conceptus signalling
      events. Maternal and conceptus-derived steroid hormones, growth factors and
      cytokines, as well as integrins and their ligands, have important and inter
      related roles in mediating adhesion between apical aspects of conceptus
      trophectoderm and maternal uterine luminal epithelium that leads to formation of
      an epitheliochorial placenta. Integrin receptors appear to play fundamental roles
      in the implantation cascade and may interact with extracellular matrix molecules
      and other ligands to transduce cellular signals through autocrine and paracrine
      mechanisms. Functional in vitro analyses can be used to monitor individual
      contributions of specific integrin receptors and ligands to the signalling
      cascades of the maternal-conceptus interface. Integrative studies of implantation
      in pigs, using in vivo and in vitro approaches, are required to understand
      conceptus attachment and implantation in this species, and provide valuable
      opportunities to understand the fundamental mechanisms of implantation in all
      species.

PMID- 11980191
TI  - Histological and immunohistochemical events during placentation in pigs.
AB  - The early morphological events in pig placental development are summarized and
      related to the known data on differences in placental vascular efficiency between
      Meishan and US breeds. The activation and localization of a number of factors,
      the ligands and their receptors, such as insulin-like growth factor (IGF),
      transforming growth factor beta (TGF beta), platelet-derived growth factor (PDGF)
      and vascular endothelial growth factor (VEGF), as well as retinoids and calcium,
      is described. The comparison between these factors gives a strong impression of
      their complex interactions and hormonal relationships during placentation and
      vascular development in pigs. This review also emphasizes that retinoids are of
      great importance for placental function and that the transport of vitamin A
      appears to take place in the areolar gland complex only, whereas based on
      histochemistry and electron energy dispersive analysis, the calcium transport may
      be confined to the interareolar route across the interhaemal barrier.

PMID- 11980192
TI  - Comparative aspects of placental efficiency.
AB  - Litter size is often proposed as the trait that could have the greatest impact in
      improving reproductive efficiency of pigs. Efforts to select directly for
      increased litter size have generally been unsuccessful and highly variable. As a
      result, several attempts have been made to identify critical physiological
      components that control litter size, with the underlying assumption that
      augmenting these components would improve this important trait. One attempt at
      improving physiological components has involved the selection of animals for
      increased uterine capacity, as measured by the number of fetuses or piglets that
      a female can carry successfully to term. Recent evidence indicates that one
      critical component of the uterine capacity in pigs is placental efficiency, or
      the body weight of a piglet divided by the mass of its placenta. It is easy to
      determine the average placental efficiency in a litter, but variation among
      conceptuses within a litter for this trait can be substantial, leading to the
      conclusion that placental efficiency is an individual conceptus trait. It is
      suggested that the limited success of selection for an increased uterine capacity
      results, at least in part, from a misguided view that 'uterine capacity' is
      strictly a maternal trait. Uterine capacity is better defined as the mass of
      placental tissue that a pregnant female can support to term, and involves
      phenotypic variation in both the dam and her offspring. This definition of
      uterine capacity allows maximization of both uterine size and placental
      efficiency in future attempts to increase litter size in pigs.

PMID- 11980193
TI  - Causes and consequences of fetal growth retardation in pigs.
AB  - In pigs, as in other species, fetal growth retardation is associated with reduced
      birth weight and increased risk of fetal and neonatal death. As there are few
      opportunities after birth to remedy the detrimental effects of low birth weight,
      it is important to understand both the intrinsic and extrinsic factors associated
      with inadequate fetal growth and to determine when growth retarded fetuses
      deviate from the growth trajectory of their normal sized littermates.
      Inadequately grown pig fetuses can be identified statistically as early as day 30
      of the 114 days of gestation, indicating that limited uterine space is not a
      primary determinant of fetal growth. Comparisons of the smallest fetus within a
      litter with a normal sized sibling reveal that inadequately grown fetuses have
      altered endocrine status and lower circulating concentrations of many essential
      amino acids. In addition, the placenta supplying the smallest fetus is
      disproportionately small and has a reduced capacity to transport amino acids.
      Understanding the timing and the causes of fetal growth retardation in pigs may
      help us to devise appropriate strategies to reduce the incidence and hence the
      detrimental postnatal consequences of runting.

PMID- 11980194
TI  - Prenatal development as a predisposing factor for perinatal losses in pigs.
AB  - The pig industry is confronted with substantial losses due to piglet mortality.
      With 3-8% stillbirths and generally > 10% preweaning mortality, approximately one
      fifth of all fetuses formed fully at the end of gestation die before weaning.
      Most of these losses occur in the perinatal period. Overall prenatal development
      (birth weight) and specific prenatal developmental and maturational processes in
      late gestation are predisposing factors for perinatal losses. Birth weight and
      variation in birth weight remain important risk factors for perinatal mortality.
      Genetic selection against piglet mortality will not necessarily increase birth
      weight but will affect body composition and proportional organ development. Many
      maturational processes that occur in late gestation in preparation for
      extrauterine life, for example specific biochemical changes in the
      gastrointestinal tract, are influenced by glucocorticosteroids and are,
      therefore, dependent on maturation of the pituitary-adrenal system. The
      carbohydrate metabolism of perinatal piglets is related closely to viability in
      the perinatal period. The prenatal deposition of carbohydrate reserves (glycogen)
      and prenatal effects on perinatal glucogenic capacity, glucose homeostasis,
      carbohydrate metabolism and thermostability are reviewed.

PMID- 11980195
TI  - Endocrine regulation of periparturient behaviour in pigs.
AB  - Pigs begin behavioural preparations for birth about 1-2 days before parturition.
      Prepartum sows wander to select a suitable site and then construct a maternal
      nest. The signal that initiates this behavioural cascade probably results from
      fetal maturation but is unknown. However, endogenous PGF2 alpha appears to be
      involved early on in an endocrine pathway that projects to the brain and can
      generate most of the prepartum behavioural components. This period of intense
      activity is followed by a quiescent phase of lying in the nest for some hours
      before fetal ejection occurs. Feedback from a completed nest or abdominal
      discomfort may both contribute to the end of nest building. In the postpartum
      phase, sows have to deal with the apparently conflicting drives of remaining
      passive to reduce accidental or deliberate damage to piglets, while at the same
      time responding actively to their needs. In commercial environments, animals
      frequently fail in this task. Although environmental influences on piglet
      survival have received much experimental attention, the genetic, social and
      endocrine drives that control sow behaviour after parturition remain poorly
      understood and their clarification is a major challenge for the future.

PMID- 11980196
TI  - Applying functional genomics research to the study of pig reproduction.
AB  - Functional genomics is an experimental approach that incorporates genome-wide or
      system-wide experimentation, expanding the scope of biological investigation from
      studying single genes to studying potentially all genes at once in a systematic
      manner. This technology is highly appealing because of its high throughput and
      relatively low cost. Furthermore, analysis of gene expression using microarrays
      is likely to be more biologically relevant than the conventional paradigm of
      reductionism, because it has the potential to uncover new biological connections
      between genes and biochemical pathways. However, functional genomics is still in
      its infancy, especially with regard to the study of pig reproduction. Currently,
      efforts are centred on developing the necessary resources to enable high
      throughput evaluation and comparison of gene expression. However, it is clear
      that in the near future functional genomics will be applied on a large scale to
      study the biology and physiology of reproduction in pigs, and to understand
      better the complex nature of genetic control over polygenic characteristics, such
      as ovulation rate and litter size. We can look forward to generating a
      significant amount of new data on differences in gene expression between
      genotypes, treatments, or at various temporal and spatial coordinates within a
      variety of reproductively relevant systems. Along with this capability will be
      the challenge of collating, analysing and interpreting datasets that are orders
      of magnitude more extensive and complex than those currently used. Furthermore,
      integration of functional genomics with traditional genetic approaches and with
      detailed analysis of the proteome and relevant whole animal phenotypes will be
      required to make full use of this powerful new experimental paradigm as a
      beneficial research tool.

PMID- 11980197
TI  - Cloning pigs: advances and applications.
AB  - Although mouse embryonic stem cells have been used widely for over a decade as an
      important tool for introducing precise genetic modification into the genome,
      demonstrating the great value of this technology in a range of biomedical
      applications, similar technology does not exist for domestic animals. However,
      the development of somatic cell nuclear transfer has bypassed the need for
      embryonic stem cells from livestock. The production of offspring from
      differentiated cell nuclei provides information and opportunities in a number of
      areas including cellular differentiation, early development and ageing. However,
      the primary significance of cloning is probably in the opportunities that this
      technology brings to genetic manipulation. Potential applications of gene
      targeting in livestock species are described with particular emphasis on the
      generation of pigs that can be used for xenotransplantation, and the production
      of improved models for human physiology and disease. The development of
      techniques for somatic cell nuclear transfer in pigs and the challenges
      associated with this technology are also reviewed.

PMID- 11980198
TI  - Deep intrauterine insemination and embryo transfer in pigs.
AB  - A new method for non-surgical deep intrauterine catheterization of pigs, without
      sedation of the sow, is described. Insemination results obtained with this method
      using fresh spermatozoa demonstrate that, in comparison to conventional
      artificial insemination (AI) (3 x 10(9) spermatozoa in 80-100 ml), a 20-60-fold
      reduction in the number of spermatozoa inseminated and at least a 8-10-fold
      reduction in the dose volume can be used without affecting fertility if
      spermatozoa are deposited deep (middle or upper) into one of the uterine horns.
      Results from deep intrauterine insemination with frozen-thawed spermatozoa and
      flow-sorted spermatozoa are also presented and the effect of deep intrauterine
      insemination on sperm transport is discussed. In addition, a brief description of
      the advances made in non-surgical embryo transfer technology is reported.

PMID- 11980199
TI  - Ovarian follicular growth in sows.
AB  - The resumption of ovarian follicular development during lactation and after
      weaning in sows is a complex process that ultimately determines rebreeding
      efficiency of sows. Ovarian follicular development before weaning is
      heterogeneous because multiple patterns of development are observed when
      individual sows are compared. Sows can have relatively inactive ovaries before
      weaning with follicles of < 2 mm in diameter. Other sows have non-ovulatory
      follicular waves in which follicles grow to approximately 5 mm and subsequently
      regress before weaning. Sows may also have preovulatory follicular development
      and ovulation, or may develop cystic ovaries before weaning. Weaning is a random
      event relative to follicular development on the ovary. Therefore, variation in
      the weaning to oestrus interval in sows is caused by weaning at random stages of
      follicular development. Most sows experience a rapid period of follicular growth
      after weaning and return to oestrus within 3-7 days. Delayed intervals to oestrus
      after weaning are associated with inactive ovaries before weaning (follicles < 2
      mm in diameter) or weaning during the regression phase of a follicular wave. An
      integrated model for follicular growth and oestrus in weaned sows should include
      endocrine mechanisms (that is, individual differences in insulin, insulin-like
      growth factor I (IGF-I), LH and FSH), behavioural mechanisms (relationship
      between follicular growth and the initiation of oestrus) and morphological
      mechanisms (that is, timing of weaning relative to ovarian follicular
      development).

PMID- 11980200
TI  - Transgenic alteration of sow milk to improve piglet growth and health.
AB  - There are many potential applications of transgenic methodologies for developing
      new and improved strains of livestock. One practical application of transgenic
      technology in pig production is to improve milk production or composition. The
      first week after parturition is the period of greatest loss for pig producers,
      with highest morbidity and mortality attributed to malnutrition and scours.
      Despite the benefits to be gained by improving lactation performance, little
      progress has been made in this area through genetic selection or nutrition.
      Transgenic technology provides an important tool for addressing the problem of
      low milk production and its detrimental impact on pig production. Transgenic pigs
      over-expressing the milk protein bovine alpha-lactalbumin were developed. alpha
      Lactalbumin was selected for its role in lactose synthesis and regulation of milk
      volume. Sows hemizygous for the transgene produced as much as 0.9 g bovine alpha
      lactalbumin l-1 pig milk. The outcomes assessed were milk composition, milk yield
      and piglet growth. First parity alpha-lactalbumin gilts had higher milk lactose
      content in early lactation and 20-50% greater milk yield on days 3-9 of lactation
      than did non-transgenic gilts. Weight gain of piglets suckling alpha-lactalbumin
      gilts was greater (days 7-21 after parturition) than that of control piglets.
      Thus, transgenic over-expression of milk proteins may provide a means for
      improving the lactation performance of pigs.

PMID- 11980201
TI  - Cryopreservation of pig embryos: adaptation of vitrification technology for
      embryo transfer.
AB  - Great advancements in cryopreservation of pig embryos have been made since the
      last International Conference on Pig Reproduction (ICPR). In 1997, there were
      standard methods to cryopreserve germplasm and embryos of most livestock species,
      except for the pig, and development of this technology for use in the
      international pig industry was slow and in the early stages. Since 1997, there
      have been advancements in cryopreservation of pig embryos, with reports of
      production of live offspring after transfer of frozen-thawed and vitrified-warmed
      pig embryos. This review summarizes the progress in cryopreservation of pig
      embryos since 1997. Cellular and molecular biology have been used to understand
      the hypothermic sensitivity of pig embryos. Development of delipation technology
      has provided the first evidence that intracellular lipids are linked to
      hypothermic sensitivity. Cytoskeletal stabilization and vitrification have led to
      the production of live offspring from vitrified-warmed and transferred embryos.
      Recently, technology has been developed for cryopreservation of pig morulae.
      Development of open pulled straws has provided more rapid rates of cooling during
      vitrification and has been effective for cryopreservation of pig embryos.
      Although improvements and refinements of the technologies will continue, it is
      now time for the pig industry to consider cryopreservation of pig embryos as a
      tool for pig production and for propagation of select herd genetics, while
      maintaining germplasm resources for the future.

PMID- 11980202
TI  - Formation and early development of the corpus luteum in pigs.
AB  - Numerous corpora lutea form from the multiple follicles that ovulate during the
      oestrous cycle of pigs. Vascular elements invade the follicle from the theca
      compartment, first centripetally, and subsequently by lateral branching of
      centripetal veins and arteries. The vessels are the vehicle for dispersion of
      steroidogenic theca cells throughout the corpus luteum. Mitosis occurs in both
      the theca and granulosa layers before ovulation, and in luteal cells well into
      the luteal phase. Luteal cell proliferation undergoes gradual restriction as the
      corpus luteum matures, but the mechanisms of exit from the cell cycle are
      unknown. The extracellular ligands that direct luteinization and maintain the
      corpus luteum include LH, prolactin, insulin and insulin-like growth factors
      (IGFs). These ligands induce qualitative and quantitative changes in steroid
      output, with progesterone as the principal product. These changes upregulate the
      cholesterol synthetic pathways to increase substrate availability. The
      intracellular regulation of luteinization is complex. A model is presented in
      which LH stimulates arachidonic and lineoleic acid metabolism to produce ligands
      for the nuclear proteins of the peripheral peroxisome activator receptor family.
      These ligands have downstream effects on cell differentiation and exit from the
      cell cycle. Luteal function is maintained by interactions among ligands,
      cholesterol regulatory proteins and constitutively expressed and regulated
      transcription factors.

PMID- 11980203
TI  - Mammalian gonadal differentiation: the pig model.
AB  - In mammals, testicular differentiation is initiated by SRY (the sex-determining
      region of the Y chromosome) gene expression in Sertoli cell precursors, followed
      by upregulation of the SOX9 gene (SRY-related HMG box gene 9). Subsequently,
      differentiated testis produces two hormones that induce sexual differentiation of
      the internal and external genital tract. Knowledge of the molecular mechanisms
      involved in gonadal differentiation has increased greatly over the past decade.
      Several genes are involved in genital ridge formation in both sexes, and others
      act specifically in testicular or ovarian developmental pathways. As for other
      mammals, relatively few data are available on the first steps of ovarian
      differentiation in pigs. In this review, the expression profiles of most genes
      known to be involved in gonadal differentiation in pigs will be presented and
      compared with those observed in mice. The main feature of gonadal differentiation
      in the pig is fetal steroidogenesis, especially cytochrome P450 aromatase gene
      organization and expression. Another specific feature of gonadal differentiation
      in pigs is the appearance of numerous cases of XX sex-reversed animals. This
      intersex condition occurs as early as day 50 after coitus, during embryogenesis,
      and appears to be triggered genetically. It leads to a wide range of phenotypes,
      strikingly similar to those observed in humans. Identification of the genes
      involved in this pathology will improve our knowledge of mammalian gonadal
      differentiation and may allow the eradication of this genetic disease in pigs.

PMID- 11980204
TI  - In vitro development of pig preantral follicles.
AB  - A limiting factor to realizing the full potential of many of the new reproductive
      techniques is the lack of abundant numbers of fertilizable oocytes. This problem
      could be addressed by using the large source of oocytes available from preantral
      and primordial follicles by developing systems for in vitro growth. In vitro
      systems that use early growing follicles as a source of oocytes have been
      developed for laboratory species and these have been successful in producing live
      young. If successful, in vitro growth in association with in vitro maturation
      (IVM) and cryopreservation would optimize in vitro production systems. In vitro
      growth systems that support the growth of pig preantral follicles have been
      developed and have been successful in producing meiotically competent oocytes
      but, to date, no live young have been produced. However, these systems remain to
      be characterized and their main application is as experimental models to study
      the processes of early oocyte and follicle development. This review provides an
      overview of culture systems that have been developed for domestic species and
      discusses how these are furthering our basic knowledge of early follicular
      development, as well as considering the benefits and potential problems
      associated with in vitro growth systems.

PMID- 11980205
TI  - Maturation of pig oocytes in vivo and in vitro.
AB  - In this review the concept that the origins of embryonic failure occur during
      oocyte development is explored. The four factors that determine oocyte viability,
      namely a normal growth phase, adequate follicle cell support during maturation,
      the completion of intracellular reprogramming before fertilization and the
      functioning of oocyte surveillance mechanisms, form the four sections of this
      review. The viability of pig oocytes at the end of the growth phase is
      compromised by presumptive spontaneous meiotic progression and by morphological
      heterogeneity. Determining the percentage and identity of viable dictyate
      oocytes, and identifying the reasons for the loss of viability, are key areas of
      future investigation. Although the requirement for follicle cell support during
      maturation is already established, little is yet known about the underlying
      signals and their transmission to the oocyte. The analysis of the action and
      nature of somatic signals will provide the foundation for further advances in the
      maturation of oocytes in vitro. Signalling cascades in oocytes control both the
      translation of masked mRNA and the modification and spatial localization of
      resultant proteins. The interdependent nature of this control system explains why
      inappropriate signals during maturation lead to subsequent embryonic mortality.
      Chromosomal errors during meiosis and early mitosis accumulate because of the
      leaky nature of the checkpoint system during the maternally regulated part of
      development: effective cell cycle surveillance is established only after the
      activation of the embryonic genome. In summary, we emphasize that the quality of
      the dictyate oocyte and the provision of appropriate signals in vitro are the
      principal determinants of maturational success.

PMID- 11980206
TI  - Children's services. Support for children's nurses.

PMID- 11980207
TI  - Changing practice. Overcoming resistance in a specialist community palliative
      care team.

PMID- 11980208
TI  - Delayed discharges. The legal implications.

PMID- 11980209
TI  - Error making. Part 2: Identifying the causes in nursing.

PMID- 11980210
TI  - Building portfolios.

PMID- 11980211
TI  - Leading the nursing agenda.

PMID- 11980212
TI  - The joy of nursing. Dr Beverly Malone: LPNS Lecture 2001.

PMID- 11980213
TI  - From rhetoric to reality. Part 2.

PMID- 11980214
TI  - Assessing the health promotion needs of informal carers.

PMID- 11980215
TI  - Instrumental passivity: a behavioural theory of dependence.

PMID- 11980216
TI  - Nutrition and the older adult.
AB  - The importance of ensuring adequate nutrition in older people is often
      acknowledged but, the evidence suggests, theory is not always matched by
      practice. This article describes causes of malnutrition in older adults and
      discusses nursing strategies to prevent it occurring.

PMID- 11980217
TI  - Out to pasture?

PMID- 11980218
TI  - How the other half lives.

PMID- 11980219
TI  - Infection control.

PMID- 11980220
TI  - As Managed Care turns 10, where we goofed, where we called it.

PMID- 11980221
TI  - Universal care making rounds in state houses and on ballots.

PMID- 11980222
TI  - Medically, race means nothing.

PMID- 11980223
TI  - HMOs have stake in quelling anger at drug store counters.

PMID- 11980224
TI  - Medicare+Choice: uncertain future for unstable program.

PMID- 11980225
TI  - Where do no harm meets the right thing to do.

PMID- 11980226
TI  - HMOs should prepare now to get handle on injectables.

PMID- 11980227
TI  - Cross-border traffic highlights differences in U.S., Canadian systems.

PMID- 11980228
TI  - The effect of practitioner compensation on HMO consumer satisfaction.
AB  - PURPOSE: To test the hypothesis that a health maintenance organization (HMO)
      consumer's satisfaction depends on the way his or her health plan compensates
      practitioners. DESIGN: Consumer Assessment of Health Plans (CAHPS) survey data
      from 1999 and 2000 were provided by the Office of Public Insurance Counsel for
      the state of Texas. These data were combined with the Health Plan Employer Data
      and Information Set (HEDIS) quality measures of managed care health plans in
      Texas published by the Texas Health Care Information Council. METHODOLOGY: The
      study fitted the CAHPS survey data to an ordered-probit model. The dependent
      variable was customer satisfaction with the health plan, using a rating scale
      from 0-10. The independent variables included the percentage of health plan
      practitioners compensated with capitated fees, the percentage compensated with a
      bonus or withholding incentive, and other health plan and consumer
      characteristics. PRINCIPAL FINDINGS: Consumer satisfaction with HMOs is
      negatively correlated with the percentage of practitioners who are compensated on
      a capitated-fee basis and positively correlated with the percentage of
      practitioners compensated with a fee-withholding incentive (e.g., a fraction of
      fees that are withheld until specific quality and cost-control goals are
      reached). Neither the percentage compensated under a bonus incentive system nor
      the percentage of general practitioners with board certification correlated with
      HMO consumer satisfaction. CONCLUSION: A managed health plan's method of
      practitioner compensation can affect participant satisfaction in a predictable
      manner.

PMID- 11980229
TI  - Keep your Web content fresh.

PMID- 11980230
TI  - Does quality of care matter? You bet!

PMID- 11980231
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 requirements
      for the production and 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 Committee's attention and
      provides information on the status and development of reference materials for
      various antibodies, antigens, blood products and related substances, cytokines,
      growth factors, and endocrinological substances. The second part of the report,
      of particular relevance to manufacturers and national control authorities,
      contains recommendations for the production and control of oral poliomyelitis
      vaccine, an amendment to the requirements for meningococcal polysaccharide
      vaccine, and a decision-tree for setting priorities in the development of
      reference materials. Also included is an addendum to the guidelines for the
      preparation, characterization, and establishment of standards and reference
      reagents for biological substances.

PMID- 11980232
TI  - [Particular features of atypical jobs].

PMID- 11980233
TI  - [Teleworking].

PMID- 11980234
TI  - [Teleworking: analysis of new prospects].

PMID- 11980235
TI  - [Temporary work: considerations after 3 years of the approval of Law No.
      196/1997].

PMID- 11980236
TI  - ["Atypical jobs" and I.N.A.I.L. protection].

PMID- 11980237
TI  - [Health and prevention in atypical jobs].

PMID- 11980238
TI  - [Health protection of workers employed in atypical jobs].

PMID- 11980239
TI  - [Temporary work in the Val d'Elsa of Siena].

PMID- 11980240
TI  - [Survey of the problems associated with teleworking of a sample of 41 employees
      working in commercial activities of the chemical oil industry].

PMID- 11980241
TI  - [Health surveillance for temporary jobs: legislative references and methodologic
      features].

PMID- 11980242
TI  - [Exposure to cosmic radiation among aeronautic staff].

PMID- 11980243
TI  - Introduction: a survey of international ethics practices in pharmacoepidemiology
      and drug safety.

PMID- 11980244
TI  - Research as a visiting doctor in Afghanistan and Cambodia.
AB  - This paper describes research I conducted into health care and its difficulties
      while working as a visiting doctor in two developing countries. The research was
      conducted in the Departments of Medicine, University Hospital, Jalalabad,
      Afghanistan, in 1994 and 1995, and Calmette Hospital, Phnom Penh, Cambodia, in
      1997 and 1998. In Afghanistan I did an observational study of medical practice
      and case studies at the Department of Medicine, and a survey of drugs sold in
      pharmacies in Jalalabad. In Cambodia I surveyed hemoglobin concentrations of
      medical patients, and did an observational study of medical practice and case
      studies at Calmette Hospital. I surveyed the body weight of medical patients in
      relation to drug doses, and used a questionnaire to survey prescribing practices
      of physicians. Each project was conducted by me alone and was completed within 1
      3 months. The support by the hospital was good and there where no ethics
      committees that had to approve the projects. Only verbal consent from the
      patients had to be obtained and no national laws or regulations affected the
      research. Small clinical research projects in developing countries are relatively
      easy to perform, if conducted by one researcher working in a hospital and not
      relying on special equipment such as a computer.

PMID- 11980245
TI  - Privacy considerations in the context of an Australian observational database.
AB  - Observational databases are increasingly acknowledged for their value in clinical
      investigation. Australian general practice in particular presents an exciting
      opportunity to examine treatment in a natural setting. The paper explores issues
      such as privacy and confidentiality--foremost considerations when conducting this
      form of pharmacoepidemiological research. Australian legislation is currently
      addressing these exact issues in order to establish clear directives regarding
      ethical concerns. The development of a pharmacoepidemiological database arising
      from the integration of computerized Australian general practice records is
      described in addition, to the challenges associated with creating a database
      which considers patient privacy. The database known as 'Medic-GP', presently
      contains more than 950,000 clinical notes (including consultations, pathology,
      diagnostic imaging and adverse reactions) over a 5-year time period and relates
      to 55,000 patients. The paper then details a retrospective study which utilized
      the database to examine the interaction between antibiotic prescribing and
      patient outcomes from a community perspective, following a policy intervention.
      This study illustrates the application of computerized general practice records
      in research.

PMID- 11980246
TI  - Ethical issues in pharmacoepidemiological research in Belgium.
AB  - PURPOSE: To illustrate the ethical issues faced in pharmacoepidemiological
      research in Belgium. METHODS: The experience with three studies is described. The
      studies concern the use of drugs for euthanasia in medical practice,
      cytomegalovirus infection in single solid organ transplants and a comparison of
      benzodiazepine use in the general population and in acute self-poisoning.
      RESULTS: With some creativity, it was possible to meet the requirements of the
      ethics committees and the law on computer databases, e.g. by bringing data
      validation closer to the data entry process, by assuring anonymity in mailing
      procedures, or by deleting identification labels as soon as they are no longer
      necessary. CONCLUSIONS: The existing juridical vacuum has not really impeded
      pharmacoepidemiological research.

PMID- 11980247
TI  - Ethical issues in a Brazilian hospital.
AB  - PURPOSE: The objective of this paper is to discuss ethical issues such as data
      protection, confidentiality, and patient freedom taking two ongoing studies as
      examples. METHODS: The two studies are being carried out at a public hospital in
      southern Brazil. Study 1 evaluates inadequate use of drugs (mainly vancomycin)
      and aims at reviewing criteria for drug use control. It includes records of 100
      patients whose prescriptions are dispensed at the hospital's pharmacy. A major
      ethical concern in this study was to ensure data confidentiality. Study 2
      evaluates treatment adherence by hypertension patients with a focus on
      hydrochlorothiazide. Here, in addition to data protection, a major ethical
      concern was the ability of patients to understand the informed consent form and
      therefore freely enter or refuse to enter the study. Both projects were approved
      by the Institutional Review Board at Hospital de Clinicas de Porto Alegre.
      RESULTS: In both studies, data confidentiality is ensured by the removal of all
      personal information from the forms used for data analysis. In Study 2,
      readability of the informed consent was considered adequate by the IRB for the
      population served by the clinic, and one-third of the patients who were contacted
      agreed to participate in the study. CONCLUSIONS: To obtain reliable results,
      basic ethical principles must be observed throughout the planning and execution
      of research projects, whether data are obtained from medical records or from
      actual interaction with patients. Thus, monitoring by an Institutional Review
      Board or equivalent is of paramount importance.

PMID- 11980248
TI  - Ethical issues in pharmacoepidemiologic research using Saskatchewan
      administrative health care utilization data.
AB  - PURPOSE: To describe the process of obtaining access to the administrative health
      care utilization data of the Canadian province of Saskatchewan and the ethical
      issues involved. METHODS: The report focuses on the process of obtaining data for
      two recent studies. In the first, associations between aplastic anemia and
      agranulocytosis and prior drug use were evaluated, while the second is an
      examination of anti-arrhythmia drug utilization. In these studies, data from
      files containing computerized information on prescription drug use,
      hospitalizations, physician services and cancer registrations were linked
      together and also with information from hospital charts, physician records and
      death registrations. RESULTS: Data on individual patients are available from the
      Saskatchewan data-files after the removal of identifying variables, and access to
      external information from hospitals, physicians, death registrations and the
      patients themselves is possible. However, researchers must accept that data
      considered to be only indirectly relevant to the objectives of the study or
      which, due to small numbers, may potentially identify either patients or
      physicians will only be released in aggregate form. CONCLUSIONS: Access to the
      Saskatchewan data-files and to external information from hospitals, physicians
      and death registrations is normally straightforward. Restrictions that are
      applied are discussed.

PMID- 11980249
TI  - Ethical challenges in pharmacoepidemiological research in Colombia.
AB  - PURPOSE: To illustrate and to discuss some ethical challenges encountered during
      pharmacoepidemiological research in a developing country (Colombia), as well as
      the decisions made to solve them. METHODS: The authors in Bogota describe three
      recent studies. The first one collected data from clinical records to evaluate
      the prescriptions patterns in recently graduated physicians. The second used an
      interrupted time series design, with a set of observations prior and after a
      combined intervention, to assess whether it improved the quality of intravenous
      antibiotic prescribing practices in a university-based hospital. The third
      evaluated pharmacists' advice in childhood acute respiratory infection and acute
      diarrhea through a community survey, followed by focus groups and in-depth
      interviews of key informers. RESULTS: The ethical issues raised by these studies
      include the need for obtaining informed consent from participants (physicians in
      Study 1 and drug sellers in Study 3), deciding when to intervene in case of gross
      prescription mistakes detected during the collection of data as part of the time
      series assessment (Study 2), the use of simulated clients to collect data in the
      community survey, and the use of study resources to buy, in some cases, useless
      medications (Study 3). CONCLUSION: Although ethical challenges in
      pharmacoepidemiology in non-industrialized countries like Colombia may be
      different from those in developed nations, ethical principles that guide research
      remain the same. The processes to safeguard these principles in Colombia for
      virtually all research are also universal in nature, and include the ethical
      review committee, subject privacy, informed consent, and disclosure of funding
      sources.

PMID- 11980250
TI  - Conducting pharmacoepidemiologic research in Denmark.
AB  - Denmark has one of the worlds most comprehensive registration of its citizens'
      use of medical and social services. Most databases are population-based and of
      very high quality. Virtually all employ a mutual person identifier, which renders
      it technically possible to link any of them with others. There are two
      prescription registries of interest for research, the OPED and the NJPD, each
      covering 0.5 million persons. The content of these are described in brief. The
      most recent Danish data protection act can be viewed as a liberalization of
      prevailing registry practice. Our most important obstacles for performing record
      linkage studies are costs, academic resources and a lack of generally accepted
      guidelines on the ethics of observational research.

PMID- 11980251
TI  - Data safety and drug safety in Germany: a closing gap?
AB  - Pharmacoepidemiology and drug utilization research are more and more involved in
      a fundamental conflict with data privacy regulations in Germany. In an attempt to
      close this gap, a working group of German data protection commissioners and
      representatives from epidemiologic research societies published guidelines on
      epidemiology and data protection, which are briefly reviewed. There are several
      data sources for drug utilization research and pharmacoepidemiology in Germany
      (national health surveys, routine data from hospitals, general practitioners, or
      statutory health insurance companies) allowing descriptive and analytic
      epidemiologic studies. Furthermore, since 1980 a random sample of all
      prescriptions of patients from statutory health insurances (GKV
      Arzneimittelindex) is analysed to produce an annual report on prescription drug
      use. More intensive use of health insurance data for evaluation of medical care
      including drug prescriptions is in discussion. The MediPlus (IMS HEALTH) database
      on 400 general and internal medicine practices provides an example to close the
      gap between the current demand for drug safety studies and data privacy issues.
      Finally, large provider systems with enormous data storage and data flow are
      emerging. Therefore, a further development of policies to guarantee ethically
      correct use of personally identifiable health data in the changing health care
      environment is urgently required.

PMID- 11980252
TI  - Ethical issues arising in pharmacoepidemiologic research in a community hospital
      in Crete, Greece.
AB  - This paper presents the various issues encountered in planning, designing,
      performing, and reporting pharmacoepidemiologic research. Five hundred and fifty
      one indigent patients insured by Social Care visited the Hospital Pharmacy of
      Chania General Hospital, and were compared with 551 patients insured under Social
      Security funds who visited three community pharmacies. The study had no external
      funding. Before we started the study, we officially sought approval from the
      Scientific Committee of our Hospital and from the local Pharmaceutical
      Association. We asked also for approval from the Medical School of the University
      of Crete. Patient privacy was of great concern in the design and performance of
      the study. The law in Greece, according to the directives of European Union,
      affects the way we use records in hospitals and protect patient rights. After
      these studies were completed, we made proposals to the authorities concerning
      continuous health education for both patients and health workers.
      Pharmacoepidemiologic research is difficult in hospitals outside universities or
      institutions, because of the lack of adequate funding and grants to support
      research staff.

PMID- 11980253
TI  - The ethical issues of the postmarketing surveillance of drug teratogenicity in
      Hungary.
AB  - PURPOSE: To discuss some ethical issues of the postmarketing surveillance of drug
      teratogenicity. METHODS: To describe the three study groups of the Hungarian Case
      Control Surveillance of Congenital Abnormalities with the three sources of data
      collection. RESULTS: This large population-based surveillance system comprised
      22,843 cases with congenital abnormalities, 38,151 population controls without
      congenital abnormalities and 834 patient controls with Down syndrome between 1980
      and 1996. The major ethical issue is connected with personal data protection
      (confidential handling of data and informed consent). However, the Hungarian
      experiences displayed the ethical dilemma between the balance of individual and
      community rights and interest (mandatory notification, mandatory autopsy of
      infant deaths, personal identification number). Finally the medical consequences
      of publication bias at the evaluation of drug teratogenicity are presented as
      these also have some ethical aspects. CONCLUSION: The ethical issues of
      postmarketing surveillance of drug teratogenicity show similarities with general
      epidemiological research but this public health system also has some special
      aspects.

PMID- 11980254
TI  - Pharmacoepidemiology--an Irish perspective.
AB  - The Irish healthcare system is a mixture of free, state-supported and private
      medicine. The state-supported General Medical Services (GMS) scheme maintains a
      large prescription database, which has been used to conduct
      pharmacoepidemiological studies in Ireland. The dataset is anonymized thus
      maintaining patient and prescriber confidentiality. Three recent studies using
      this data are described, two of which outline the effect of regulatory advice and
      the media on prescribing patterns and one which describes the development of an
      index of prescribing quality which may be applied to prescription data. The GMS
      prescription database is presently being complemented by a database for some 0.7
      million people who seek reimbursement for prescriptions from individuals or
      families in excess of 42 Pounds per month which together will have an important
      role for the continued development of pharmacoepidemiology in Ireland.

PMID- 11980255
TI  - Drug epidemiology in Italy: methods and ethical issues. The example of
      psychiatry.
AB  - PURPOSE: These notes aim at analysing current methods, ethical issues and major
      legislation changes related to drug epidemiology in Italy. METHODS: The design
      and conduct of two pharmacoepidemiological surveys carried out in the context of
      recent law dispositions on psychiatric care and confidentiality are presented.
      RESULTS: In 1978 law 180 stated that no more patients had to be admitted to
      psychiatric hospitals, and no more psychiatric hospitals had to be built. Chronic
      long-stay patients were allowed to remain in hospitals. In 1994, however,
      financial law 724 established a deadline for the final closure of Italian
      psychiatric hospitals. A survey of more than 1000 patients living in eight state
      psychiatric hospitals was carried out to describe the social and clinical
      characteristics of the inpatient population and to monitor their community
      placement. In 1996 law 675 established that private and confidential information
      could not be used for any purpose without the patient's informed consent.
      However, this law was not implemented that year. A survey of benzodiazepine use
      among general practice patients was conducted without written informed consent.
      CONCLUSIONS: The Italian legislation has been changing for some years, and
      regulations might still be modified in the near future. To increase ethical
      practices in pharmacoepidemiology scientists and clinical researchers should
      guarantee high standards in terms of research objectives, design and analyses.
      Potential conflict of interest should always be declared.

PMID- 11980256
TI  - Drug use investigation (DUI) and prescription-event monitoring in Japan (J-PEM).
AB  - OBJECTIVE: To present ethical issues and relevant problems in observational
      studies of drug safety in Japan. METHODS: The Pharmaceutical Affairs Law,
      associated ordinances, and notifications relevant to Drug Use Investigations
      (DUIs), and published documents for two pilot studies of prescription-event
      monitoring in Japan (J-PEM) were examined, particularly with regard to the
      protection of privacy. Information relevant to the proposed legislation intended
      to protect personal information and proposed guidelines on ethical issues in
      epidemiological studies were also collected. RESULTS AND CONCLUSION: The formal
      studies inaugurated as the 'side-effect investigations' in the late 1960s and
      replaced by those of the DUI in 1980 have been conducted by drug manufacturers,
      in accordance with the Pharmaceutical Affairs Law. The first pilot study of J-PEM
      was started in 1997 and the second one is currently operated under a Health
      Sciences Research grant, supported by the Ministry of Health and Welfare. Those
      observational studies have been conducted while maintaining the confidentiality
      of personal data, but without requiring either approval by institutional ethics
      boards or informed consent from patients. However, according to the
      Pharmaceutical Affairs Law, those involved in postmarketing surveillance studies
      must protect the privacy of study subjects and those who break this rule may be
      subject to penalties. Ethical issues associated with pharmacoepidemiological
      studies will be clearly determined in Japan before the end of 2001 when the law
      designed to protect personal information will be introduced and official
      guidelines on ethical issues in epidemiological studies will have come into
      effect.

PMID- 11980257
TI  - Privacy issues in pharmacoepidemiology: the importance of weighing costs and
      benefits.

PMID- 11980258
TI  - Privacy issues and the monitoring of sumatriptan in the New Zealand Intensive
      Medicines Monitoring Programme.
AB  - PURPOSE: The purpose of this paper is to describe how the New Zealand (NZ)
      Intensive Medicines Monitoring Programme (IMMP) functions in relation to NZ
      privacy laws and to describe the attitudes of patients to drug safety monitoring
      and the privacy of their personal and health information. METHODS: The IMMP
      undertakes prospective observational event monitoring cohort studies on new
      drugs. The cohorts are established from prescription data and the events are
      obtained using prescription event monitoring and spontaneous reporting. Personal
      details, prescribing history of the monitored drugs and adverse events data are
      stored in databases long term. The NZ Health Information Privacy Code is outlined
      and the monitoring of sumatriptan is used to illustrate how the IMMP functions in
      relation to the Code. Patient responses to the programme are described. RESULTS:
      Sumatriptan was monitored in 14,964 patients and 107,646 prescriptions were
      recorded. There were 2344 reports received describing 3987 adverse events. A
      majority of the patients were involved in the recording of events data either
      personally or by telephone interview. There were no objections to the monitoring
      process on privacy grounds. CONCLUSION: Given the fact that all reasonable
      precautions are taken to ensure privacy, patients perceive drug safety to have
      greater priority than any slight risk of breach of confidentiality concerning
      their personal details and health information.

PMID- 11980259
TI  - Pharmacoepidemiological research at the Medicines Monitoring Unit, Scotland: data
      protection and confidentiality.
AB  - The Medicines Monitoring Unit (MEMO) is a University-based organization that uses
      record-linkage techniques to construct an observational database for the
      population of Tayside, Scotland (approximately 400,000 people). This contains
      healthcare data indexed by a unique identifier, including data on all
      prescriptions dispensed, which facilitates pharmacoepidemiological (and other)
      research. It has hitherto been possible to carry out drug safety studies in the
      entire population, with access to original medical records of patients where
      necessary, that have satisfied ethical concerns and confidentiality legislation.
      However, the recent UK Data Protection Act 1998 (which enforces the 1995 European
      Directive on Data Protection) has important implications for MEMO's research. The
      Act has necessitated changes to the way in which research studies are carried
      out, with MEMO's objective being to ensure that research can continue while
      protecting the rights and privacy of individual patients. This involves
      anonymization of data, seeking specific ethical approval for research studies and
      obtaining relevant permissions from 'Caldicott Guardians', as described in this
      article.

PMID- 11980260
TI  - Systemic conditions for performance of pharmacoepidemiologic studies in Slovenia.
AB  - In Slovenia, the national health insurance system covers almost the whole
      population. The average patient receives six to seven prescriptions per year with
      an average value of 15 USD per prescription. This paper presents the systemic
      conditions necessary for the performance of pharmacoepidemiologic studies. A
      recent study addressing the use of antiepileptic drugs is an example. The current
      law on Personal Data Protection, which is compliant with EU Directive 95/46/EC,
      prevents infringement of personal integrity resulting from inappropriate use of
      personal data or inappropriate management and use of databases containing
      personal data. Since July 2000, the Law on Health Care Related Databases has
      defined the databases and the ways data can be acquired, processed, transferred,
      and exchanged among persons authorized to perform health care services. When
      gathering additional data not currently contained in the health care-related
      databases defined by the law, written consent from participants is required, and
      study documentation must be submitted for approval to the national Medical Ethics
      Committee. The main legislation covering clinical and pharmacoepidemiologic
      research is the Medicinal Products and Medical Devices Act of 1999, together with
      its by-laws, which is also in accordance with EU Directives.

PMID- 11980261
TI  - Ethical issues related to retrospective drug utilization studies in South Africa.
AB  - PURPOSE: The purpose of the manuscript is to discuss the ethical issues related
      to pharamacoepidemiological research in South Africa, with specific emphasis on
      three recently performed retrospective drug utilization studies. METHODS: Ethical
      considerations relating to three retrospective drug utilization studies on
      hyperlipidaemia, diabetes and tricyclic antidepressants are discussed. RESULTS:
      Computerized medication records were obtained from three different organizations
      after formal proposals had been submitted. The information contained in the data
      sets varied, and in some instances, a fair amount of manual coding had to be
      performed to make the data useable for research purposes. The research was not
      sponsored by the private pharmaceutical sector and this minimized the potential
      for any bias in the studies. Data privacy and confidentiality were maintained at
      all times. No patient could be traced, and it was also not possible to determine
      which medical practitioners were involved in the prescribing of the drugs.
      CONCLUSIONS: Retrospective drug utilization studies are a relatively easy,
      inexpensive and uncomplicated method to comment on the prescribing of drugs in
      large patient populations provided that ethical principles related to
      confidentiality and data privacy are adhered to.

PMID- 11980262
TI  - Ethical and legal considerations in a Swiss study on the quality of
      pharmacotherapy in the city of Basel.
AB  - We describe a study on the quality of pharmacotherapy that included downloading
      electronic records in pharmacies and obtaining other information from the Public
      Sickness Fund in Basel, Switzerland. Legal and ethical considerations were
      discussed with and approved by the Internal Review Board of the university
      clinics through which the project was organized. Technical procedures were used
      to assure anonymity of the records during data collection and for the analysis.
      Completion of the records through links with personal data could be performed
      using a legally required process for quality assurance of the Public Sickness
      Fund.

PMID- 11980263
TI  - ISPE as a balanced forum. Summary of the President's address at the International
      Conference of Pharmacoepidemiology, Toronto, 2001.

PMID- 11980264
TI  - Pharmacoepidemiology and drug safety.

PMID- 11980265
TI  - In vitro antimicrobial activity of 3,4-dihydro-s-triazinobenzimidazole
      derivatives.
AB  - Among 31 3,4-dihydro-s-triazinobenzimidazole derivatives tested 12 compounds
      showed in vitro antimicrobial activity against G+ bacteria. Best results were
      obtained with substances containing naphthyl or halogenated phenyl group on the
      triazine ring. The tested derivatives had no significant in vitro antimicrobial
      activity against either the used G- species or fungi.

PMID- 11980266
TI  - Psychoactive tryptamines from basidiomycetes.
AB  - The review lists natural sources, i.e. strains and species of fungi producing
      predominantly psychoactive tryptamines (indolealkylamines), their chemical
      structure and properties, toxic effects on the man and psychic symptoms of
      intoxication. It describes the biosynthesis and production of some tryptamines by
      the mycelial culture of Psilocybe bohemica Sebek, a survey of methods for their
      analysis and isolation. It evaluates the worldwide use and abuse of psychoactive
      fungi as sources of drugs in general and in the Czechia in particular during the
      last two and a half decades.

PMID- 11980267
TI  - A new method of colorimetric assay of beta-lactamase suitable for estimation of
      beta-lactamase inhibition in crude microbial culture filtrates.
AB  - A simple procedure is described for the rapid assay of beta-lactamases suitable
      for use in the quantitation of beta-lactamase inhibition in crude culture
      filtrates of soil microbes. The proposed method is based on measuring the blue
      reaction product (lambda max 750 nm) formed during reduction of phosphomolybdic
      acid with reducing products generated from beta-lactam hydrolysis and is not
      influenced significantly by the metabolites of microbial culture filtrates which
      often interfere with conventional beta-lactamase assay techniques.

PMID- 11980268
TI  - Identification of Streptomyces odor spectrum.
AB  - The chemical composition of odors produced by nine strains of Streptomyces was
      determined. Strains Streptomyces aureofaciens, S. avermitilis, S. cinamomensis,
      S. coelicolor, S. griseus, S. lividans, S. rimosus, S. spectabilis, S. virginiae
      (as representatives of producers of biologically active compounds) were
      cultivated at the same time statically in dishes and in shaken flasks at similar
      cultivation conditions. According to the GC-MS analysis of odor compounds, more
      than twenty noteworthy volatile chemical individuals were identified. As the main
      component of odor spectrum geosmin and homologues of oxolones (dihydrofuranones)
      were found; the other compounds (pyrazine derivatives, acetoin and its
      homologues, aromatic esters, furan derivatives, etc.) were in minority.

PMID- 11980269
TI  - Copper-resistant bacteria from industrial effluents and their role in remediation
      of heavy metals in wastewater.
AB  - Six copper-resistant bacterial strains were isolated from wastewater of tanneries
      of Kasur and Rohi Nala. Two strains tolerated copper at 380 mg/L, four up to 400
      mg/L. Three strains were identified as members of the genus Salmonella; one
      strain was identified as Streptococcus pyrogenes, one as Vagococcus fluvialis and
      the last was identified as Escherichia coli. The pH and temperature optimum for
      two of them were 7.0 and 30 degrees C, respectively; four strains had
      corresponding optima at 7.5 and 37 degrees C, respectively. All bacterial isola
      tes showed resistance against Ag+ (280-350 mg/L), Co2+ (200-420), CrVI (280-400),
      Cd2+ (250-350), Hg2+ (110-200), Mn2+ (300-380), Pb2+ (300-400), Sn2+ (480-520)
      and Zn2+ (300-450). Large-sized plasmids (> 20 kb), were detected in all of the
      strains. After the isolates were cured of plasmids with ethidium bromide, the
      efficiency of curing was estimated in the range of 60-90%. Reference strain of E.
      coli was transformed with the plasmids of the bacterial isolates which grew in
      Luria-Bertani medium containing 100 mg/L Cu2+. The capability to adsorb and
      afterwards accumulate Cu2+ inside their cells was assayed by atomic absorption
      spectrophotometer; all bacterial cells had the ability to adsorb 50-80% of the
      Cu2+ and accumulate 30-45% Cu2+ inside them after 1 d of incubation.

PMID- 11980270
TI  - Antifungal efficacy of bacteria isolated from marine sedentary organisms.
AB  - The antibiotic-producing ability of 57 bacteria isolated from 8 marine sedentary
      organisms, 6 sponges (Spirastrella sp., Phyllospongia sp., Ircinia sp., Aaptos
      sp., Azorica sp., Axinella sp.), 1 soft coral (Lobophytum sp.) and 1 alga
      (Sargassum sp.), was evaluated against 6 phytopathogenic fungi (Helminthosporium
      oryzae, Rhizoctonium solani, Pyricularia oryzae, Fusarium oxysporum, Aspergillus
      oryzae and A. fumigatus). Bacteria of the genus Bacillus (20%), Pseudomonas (33%)
      and Flavobacterium (40%) were predominant among the heterotrophic bacteria
      isolated from the marine sponges, soft coral and alga, respectively. Bioassay
      results revealed that 36 (63%) bacterial isolates displayed antifungal activity
      against at least one fungus, the alga (Sargassum sp.) being the source of highest
      number (80%) of producer strains. Twelve bacterial isolates inhibited all fungi.
      The MIC of the organic extracts of 12 bacteria ranged from 0.3 to 22.8 mg/L.

PMID- 11980271
TI  - Quantitative distribution of microbial biomass in the soil profile of a high
      mountain grassy ecosystem.
AB  - The soil microbiota of a grassy ecosystem in the subalpine belt of the Rila
      Mountain National Park showed greater amounts of fungal biomass. This remained
      relatively constant throughout the months of sampling while bacterial biomass was
      a dynamic value fluctuating within a wide range. The two groups of microorganisms
      also differed in their in-depth distribution in the soil profile: the bacterial
      biomass was relatively homogeneously distributed while the fungal biomass
      gradually decreased with depth. Good correlation between the amount of biomass
      and the values of some abiotic factors of the environment was shown by
      correlation analysis in a "warm" period of investigation; no distinct correlation
      between microbial biomass and environmental factors was observed in a "cold"
      period.

PMID- 11980272
TI  - Viability of dried filaments, survivability and reproduction under water stress,
      and survivability following heat and UV exposure in Lyngbya martensiana,
      Oscillatoria agardhii, Nostoc calcicola, Hormidium fluitans, Spirogyra sp. and
      Vaucheria geminata.
AB  - Dried vegetative filaments of Spirogyra sp., Vaucheria geminata and Nostoc
      calcicola died within 1/2, 1 and 4 h, respectively; those of Hormidium fluitans,
      Oscillatoria agardhii and Lyngbya martensiana retained under similar storage
      conditions viability for 3, 5 and 10 d, respectively. The viability of dried
      vegetative filaments of L. martensiana, O. agardhii and H. fluitans decreased on
      storage at 20 degrees C in the dark. L. martensiana and O. agardhii tolerated 0.8
      mol/L NaCl. The resistance to desiccation in L. martensiana and O. agardhii
      exhibited similar dependence as that to frost, to heat and UV light. O. agardhii
      filaments became slightly broader and their cells developed large number of gas
      vacuoles when grown in 0.8 mol/L NaCl-containing medium. The water stress imposed
      on growing algae either on high-agar solid media or in NaCl-containing liquid
      media reduced hormogonium formation in L. martensiana and O. agardhii, heterocyst
      and akinete formation in N. calcicola and fragmentation in H. fluitans; it did
      not induce conjugation in Spirogyra sp. and formation of reproductive organs in
      V. geminata. In all studied algae the stress reduced at various levels the
      survival of vegetative parts. Generally, algal body form and composition rather
      than habitats seem to decide primarily the level of resistance against various
      stress conditions.

PMID- 11980273
TI  - Factors affecting the mating competence in the unicellular green alga
      Chlamydomonas eugametos (Volvocales).
AB  - Routinely prepared gametes (by flooding 3 week-old agar cultures) showed about
      80% mating competence if the opposite sexual partners were mixed together. The
      mating competence exhibited a strict dependence on the composition of the
      solution in which the cells were suspended before mixing; it decreased
      progressively with increasing concentration of nitrates. In contrast, no
      inhibiting effect was found if urea was used as the source of nitrogen. Other
      ions present in nutrient media did not show any effect. Mating activity varied
      according to the spectral composition of light, being higher with a blue light
      than with a red one. Blue light caused accumulation of vis-a-vis pairs, which
      were blocked to form zygotes. Freshly released daughter cells in vegetatively
      grown synchronous cultures had a dual nature--vegetative and sexual one. In these
      daughter cells, similar rules were found for governing of mating competence to
      those valid for standard gametes obtained from flooded agar cultures. High mating
      competence was found in daughter cells released the during dark period in
      distilled water, nitrate-free media, in the presence of Mg2+ or Ca2+ ions, or in
      media containing urea. The conditions during which daughter cells are released
      and the conditions under which they mate can be considered crucial for expression
      of gametic nature as a mating competence.

PMID- 11980274
TI  - Occurrence and genetic association of selected virulence factors in clinical
      Escherichia coli isolates.
AB  - Occurrence of cnf1+ E. coli pathogenic strains among extraintestinal E. coli
      isolates was evaluated to explain an impact of cytotoxic necrotizing factor type
      1 (CNF1) in human infections. A total of 120 E. coli isolates were characterized
      for presence of virulence factors cnf1- and pap--specific sequences by PCR, and
      the production of alpha-hemolysin using blood agar-plate test. Different
      association patterns among the detected virulence factors were obtained by
      comparison of various groups of clinical E. coli isolates. These differences
      probably reflect a potential impact of CNF1 in the colonization of vaginal
      environment.

PMID- 11980275
TI  - Formation of iodinin by a strain of Acidithiobacillus ferrooxidans grown on
      elemental sulfur.
AB  - The presence of the pigment iodinin, an Acidithiobacillus ferrooxidans culture
      metabolite, was demonstrated after growth of bacteria on elemental sulfur. The
      structure of iodinin was confirmed by X-ray structure analysis; its physiological
      role is discussed.

PMID- 11980276
TI  - One-year mortality in elderly stable patients with COPD.
AB  - A retrospective study was performed to evaluate the risks of one-year mortality
      in very old hospitalized patients including those suffering from chronic
      obstructive pulmonary disease (COPD). Six hundred and fifty-eight disabled
      patients (M = 194, mean age 79.2 +/- 7.4 years) consecutively admitted to and
      discharged from a Geriatric Evaluation and Rehabilitation Unit (GERU) after a
      comprehensive rehabilitation program were studied and divided into two groups:
      COPD (n = 337, 51%) and non-COPD (n = 321, 49%). Multidimensional evaluation
      including information on demographics, cognitive status [Mini Mental State
      Examination (MMSE)], physical health [number of diseases, Greenfield's Individual
      Disease Severity (IDS), and number of drugs used], functional disability [Basic
      Activity of Daily Living (BADL), Tinetti scale, and Physical Performance Test
      (PPT)], and nutritional status [Prognostic Nutritional Index (PNI)] were assessed
      at admission. Survival rate was assessed over a 1-year period following
      discharge. COPD patients mainly differed from non-COPD in terms of older age,
      smoking habit, number of associated diseases and drugs used. Aggregating the IDS
      2-3-4 COPD classes (symptoms + functional impairment), the risk of one-year
      mortality was double that of the IDS 1 COPD class (symptoms only) and of non-COPD
      subjects (IDS 0 class) after adjusting for age, sex, disability, malnutrition,
      and comorbility. Moreover, IDS 2-3-4 COPD patients suffering from cor pulmonale
      (CP) had a fourfold 1-year risk of mortality in comparison with the IDS 1 COPD
      group after adjusting for the same covariates. Hospitalized stable very old COPD
      patients presenting functional impairment have a higher 1-year risk of mortality
      than only symptomatic COPD or non-COPD subjects. The presence of cor pulmonale
      with COPD further increases this risk.

PMID- 11980277
TI  - Evaluation of the POLYMESAM system in the diagnosis of obstructive sleep apnea
      syndrome.
AB  - The reliability of a POLYMESAM (PM) instrument in the detection of ventilatory
      disorders and in the diagnosis of obstructive sleep apnea syndrome (OSAS) was
      evaluated in 50 subjects suspected for OSAS, simultaneously studied by
      polysomnography (PSG) in a sleep laboratory. Recordings were analysed by separate
      scorers, blinded to the results of the paired recording. The number of central
      (Ac), obstructive (Ao) or mixed apneas (Am), of hypopneas (H), and the total
      number of ventilatory disorders (AH) per hour of time in bed (TIB) calculated on
      the two recordings were significantly correlated. Bland and Altman analysis
      showed a good agreement between AH/TIB, Ac/TIB, Am/TIB and mean AH duration; a
      lower Ao/TIB at PM was mirrored by a higher H/TIB. Forty-two subjects had OSAS
      according to an apnea/hypopnea index (AHI) > or = 10 at PSG. Due to low sleep
      efficiency, AH/TIB was substantially lower than AHI. However an AH/TIB > or = 5
      at PM showed a sensitivity of 100% and a specificity of 71.4%, while an AH/TIB >
      or = 10 showed a sensitivity of 95.2% and a specificity of 100%. In conclusion,
      PM proved reliable for recognition of the characteristics of ventilatory
      disorders and for diagnosis of OSAS.

PMID- 11980278
TI  - Reversal of airflow obstruction and improvement in cystic lesions with treatment
      of HIV associated PCP.
AB  - A 54-year-old Japanese male smoker in whom lung function had been normal
      developed airflow obstruction coincident with the development of human
      immunodeficiency virus (HIV)-associated Peumocystis carinii pneumonia (PCP).
      Chest high resolution computed tomography (HRCT) revealed cystic lesions
      involving the upper lung fields. Both cystic lesions and airflow obstruction
      improved simultaneously with treatment of PCP and acquired immunodeficiency
      syndrome (AIDS). Bronchiolar PCP lesions creating a check-valve mechanism may
      explain these reversible changes.

PMID- 11980279
TI  - Methodological aspects in the analysis of spontaneously produced sputum.
AB  - Analysis of sputum as a specimen containing inflammatory indices has gained
      considerable interest during the last decade with focus on chronic bronchitis
      (CB) with or without airway obstruction, cystic fibrosis (CF), chronic
      obstructive pulmonary disease (COPD) and asthma. The nature of the specimens
      requires expert skill for handling them and for performing analyses. The analysis
      of spontaneously produced sputum has been performed less frequently than that of
      induced sputum. This is surprising as several studies have shown that the
      collection procedures and the assay methods are highly reproducible. There are
      several valid parameters of sputum analysis that can be applied in research on
      airway inflammation and in monitoring therapy of patients. Spontaneously produced
      sputum can be obtained in a simple and non-invasive way, which warrants further
      efforts to expand the range of applications of its analysis. Here, we will
      critically review the procedures for collecting spontaneously produced sputum,
      for handling the samples, and the requirements for assay of sputum components.
      This will imply the reproducibility of the analysis, the recovery of solutes, the
      validity of assays in terms of reproducibility and of linearity of the response,
      the validity of the assays with respect to association with other inflammatory
      parameters and with clinical parameters, and the usefulness of assays with
      respect to their response upon treatment of patients.

PMID- 11980280
TI  - Induced sputum in asthma.
AB  - This is a short review of the use of induced sputum in bronchial asthma. The
      clinical applications, the procedure of this method as well as the safety
      validity and reproducibility of the results are discussed in detail. It is shown
      that sputum induction is a practical and safe procedure and an important research
      tool of local inflammation of bronchial asthma.

PMID- 11980281
TI  - Tidal breathing affects airway responsiveness to methacholine.
AB  - Asthma is characterized by increased airway responsiveness and airway
      inflammation. Airway hyperresponsiveness may be caused by increased airway smooth
      muscle contractility or by a decrease in the mechanical load that opposes airway
      smooth muscle contraction. Under static conditions, the equilibrium between
      contractility and load will determine the final airway smooth muscle length and
      therefore airway caliber. Because of tidal breathing, however, lungs normally
      function under dynamic conditions where both airway contractility and opposing
      load are affected. The capability of tidal breathing to appropriately modulate
      airway function might be the mechanism that differentiates airways of asthmatics
      from those of normal subjects.

PMID- 11980282
TI  - Role of leukotriene receptor antagonists in the management of mild-to-moderate
      asthma.
AB  - To date the position of Leukotriene Receptor Antagonists (LTRAs) in asthma is not
      yet fully established. Recent asthma guidelines consider LTRAs as 'alternative'
      to low doses of inhaled corticosteroids (ICS) for treatment of patients with mild
      persistent asthma, while in Europe LTRAs are licensed as additional therapy to
      ICS. Our aim in this paper is to review comparative studies between ICS and
      antileukotrienes in mild to moderate asthma, looking at their efficacy on asthma
      outcomes and on patient expectations (compliance, quality of life, and safety).
      Some studies report a superior efficacy of ICS, while others, in particular in
      patients aged < 12 years, found no differences. When considering patients'
      expectations LTRAs seem to be superior, with higher compliance and quality of
      life. Even if no differences in adverse effects have been found between ICS and
      LTRAs, whose safety profiles are not different from placebo, some concerns exist
      on long term treatment with ICS, even at low doses, in children and
      postmenopausal women. For this reason, even if ICS are superior to LTRAs in
      controlling asthma outcomes and in improving pulmonary function, in children and
      elderly patients LTRAs can be considered an alternative to low-dose ICS.

PMID- 11980283
TI  - Immunoglobulin-E and anti-IgE treatment in lung disease.
AB  - A highly specific monoclonal antibody binding IgE (anti-IgE/omalizumab) has made
      it possible to determine the immunopathogenetic role that this reaginic antibody
      plays in human allergic disease. It is clear from recently completed studies that
      IgE is essential to the full generation of early and late asthmatic responses in
      human bronchoprovocation trials. Importantly, anti-IgE treatment of severe asthma
      disease significantly improves symptoms and reduces exacerbation episodes.
      Elevated serum levels of IgE are prominent in the clinical presentation of
      allergic bronchopulmonary mycoses and IgE-mediated Type I hypersensitivity
      reactions are of fundamental importance to the immunopathogenesis of allergic
      bronchopulmonary aspergillosis. Although the role of IgE in mediating immunity to
      helminth parasites is considerably less clear, it is safe to conclude that the
      overall balance of evidence does not support a primary role for IgE in host
      protection with regard to schistosomiasis and strongyloidiasis.

PMID- 11980284
TI  - Impact of BAL on the diagnosis and treatment of nosocomial pneumonia in ICU
      patients.
AB  - Nosocomial pneumonia and ventilator-associated pneumonia are currently the second
      leading cause of nosocomial infections and account for approximately 10-15% of
      all hospital-acquired infections. Crude mortality rates range from 24% to 76%
      depending on the population and clinical setting studied. During the last ten
      years, several diagnostic methods have been developed to microbiologically
      confirm the clinical diagnosis, especially in mechanically ventilated patients.
      This article seeks to clarify the issues surrounding the use of invasive
      fiberoptic bronchoscopic techniques in the diagnosis and treatment of nosocomial
      pneumonia.

PMID- 11980285
TI  - Community-acquired pneumonia: role of atypical organisms.
AB  - M. pneumoniae infection occurs world-wide and is the most common cause of
      community-acquired pneumonia (CAP) in the 5 to 20 year-old age group. The most
      reliable diagnostic test is enzyme immunoassay that allows immunoglobulin (Ig)G
      and IgM titration and presents 92% sensitivity and 95% specificity on paired
      samples. Potentially active drugs are tetracyclines, macrolides, ketolides,
      lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. The
      incidence of Legionella infection, in spite of its world-wide diffusion, is
      highly variable in different studies, ranging from 1% to 27% of CAP. The most
      likely mode of transmission is direct inhalation from Legionella-contaminated
      water-supply systems. Extrapulmonary manifestations are relatively common but
      nonspecific. However, some signs and symptoms may raise the suspicion of
      Legionella infection: a sputum Gram stain with a high number of neutrophils
      without any organism, hyponatremia, and diarrhea in a critically ill patient.
      Urinary radioimmunoassay (RIA) antigen detection is the method of choice for L.
      pneumophila serogroup 1. The best treatment regimen is a full three-week
      treatment with a macrolide (erythromycin, clarithromycin, azithromycin). An
      alternative treatment regimen may be the association of second generation
      fluoroquinolones with tetracyclines. A notable improvement in most of the new
      fluoroquinolones is their activity against Legionella, so that their use as
      single agent may be hypothesised even if clinical data are still insufficient for
      a definitive indication. Chlamydia pneumoniae account for 6-20% of CAP depending
      on several factors such as setting of the studied population, age group examined,
      and diagnostic methods used. The current gold standard for serological diagnosis
      of acute infection is microimmunofluorescence testing. Tetracyclines and
      erythromycin show good in vitro activity and so far have been the most commonly
      employed drugs in the treatment of C. pneumoniae infection. New macrolides,
      ketolides, and new fluoroquinolones are other potentially effective drugs.

PMID- 11980286
TI  - Follow-up and outcomes of nasal CPAP therapy in patients with sleep apnea
      syndrome.
AB  - The large and growing numbers of patients with obstructive sleep apnea syndrome
      (OSAS) attending sleep disorders clinics create major logistical difficulties for
      the follow-up of these patients, particularly those on nasal continuous positive
      airway pressure therapy (CPAP). Follow-up of patients on CPAP should focus on
      treatment efficacy, side effects, and compliance with therapy. The adequacy and
      comfort of mask fit and the appropriate selection of pressure level at the time
      of initial titration have a major influence on treatment efficacy. Outcome
      measures of treatment efficacy include improvements in daytime performance and
      quality of life measures in addition to impact on cardiovascular morbidity,
      particularly hypertension. Side effects and compliance with CPAP are also
      influenced greatly by the adequacy of mask fit and pressure selection, which
      underlines the great importance of adequate technical expertise and patient
      education at the time of initiation of therapy. The recent development of
      automatically adjusting CPAP devices should greatly simplify the initiation of
      CPAP therapy and also the subsequent follow-up of OSAS patients on CPAP therapy.
      However, the much higher cost of auto-CPAP devices compared to standard CPAP does
      not justify the routine use of these more expensive devices at this time.

PMID- 11980287
TI  - Smoking cessation as a therapeutic and preventive intervention: a meeting report.
AB  - In November 2000, a meeting took place on "Smoking cessation as a therapeutic and
      preventive intervention". The venue of the meeting was Venice, in the old
      Monastery of the Isola San Giorgio, and it was jointly organised by the Italian
      Association of Hospital Pulmonologists (AIPO) and the European Section of the
      Society for Research on Nicotine and Tobacco (SRNT--Europe). The meeting was also
      sponsored by the European Respiratory Society (ERS). The importance of the topic
      cannot be underestimated. According to the World Health Organisation (WHO)
      tobacco smoking is the most important cause of preventable death in the
      industrialised world. When tobacco smoking constitutes a repetitive and
      compulsive behaviour, for instance when a person continues smoking when suffering
      from a smoking related disease, it is due to tobacco dependence, which both WHO
      and the American Psychiatric Association classify as a disease. Tobacco smoking
      is not only a disease in itself but can also cause other diseases, such as
      chronic obstructive lung disease, lung cancer and cardiovascular disease, and can
      worsen pre-existent disease, e.g. asthma. In the WHO European region, according
      to WHO estimates, tobacco smoking causes at least 1,200,000 deaths each year (14%
      of all deaths). So far, a preventive strategy based on protection of children and
      adolescents from initiation has not worked in decreasing the prevalence among
      young generations. Even with the best educational programs success is partial and
      ephemeral. Smoking cessation with behavioural and pharmacological aid is a well
      established therapeutic intervention, supported by strong scientific evidence.
      But smoking cessation can also be a preventive intervention, because it can
      reduce the prevalence of smokers in a community. Obviously, smoking cessation is
      to be used together with all other interventions recognized as effective in
      tobacco control (cigarette and tobacco product pricing, regulatory approaches,
      smoking bans, health education).

PMID- 11980288
TI  - Health effects of tobacco use and exposure.
AB  - Tobacco is still widely consumed in a variety of different ways, mainly as
      smokeless tobacco and cigarette smoking. Four traits characterize tobacco use
      whatever the way of using it: 1) addiction linked to nicotine is behind all the
      tobacco hazards; 2) individual variation in tobacco susceptibility; 3) dose
      response relationship; 4) time-lag effect. Smokeless tobacco, chewed or snuffed
      can lead mainly to inflammation of the oral cavity and oral cancers. Cigarette
      smoking accounts for 65-85% of global tobacco consumption. Active smoking can
      cause: 1) respiratory disorders culminating in chronic obstructive pulmonary
      disease (COPD) and emphysema; 2) cardiovascular hazards by way of increased
      vascular spasm and atherosclerosis leading to acute and chronic myocardial
      events, cerebral and peripheral vascular diseases; 3) cancers: twelve types are
      caused or related to cigarette smoking. Lung cancer is still the leading cause of
      cancer death in most high-income countries where data are available. An excess
      mortality is associated with smoking, with a 2-fold greater risk in smokers than
      in nonsmokers throughout middle age. The exposed pregnant woman subjects herself
      and her pregnancy to risks, and her fetus to growth retardation and perinatal
      morbidity and mortality. Passive smoking implicates 20-80% of the whole
      population. It can be nearly as harmful as active smoking depending upon risk
      factors, and can lead to short as well as to long-term effects. Children are the
      most vulnerable population particularly during the first years of life. Passive
      smoking increases risks for higher and lower respiratory tract illness but a
      smoke-free environment improves all these disorders. Ischemic heart diseases and
      lung cancer are the main risks for non smoking adults exposed to cigarette smoke.
      Tobacco use and exposure is the single most important source of preventable
      morbidity, disability and premature mortality. But giving up smoking helps at any
      time, the sooner the better. Health professionals should be the key advocates in
      tobacco prevention.

PMID- 11980289
TI  - Forced oscillation technique: from theory to clinical applications.
AB  - The forced oscillation technique (FOT) allows the noninvasive assessment of the
      mechanical properties of the respiratory system. Given that the technique does
      not require patient cooperation, it is suitable for the routine evaluation of
      respiratory function in a variety of clinical applications. In this paper, the
      rationale and the most conventional equipment and data processing of the
      technique are described. A number of clinical applications of FOT are briefly
      reviewed. One common use of the technique is to assess respiratory function in
      patients with different pathologies and in epidemiology. One of the most
      referenced applications of FOT is in tests of airway responsiveness to inhaled
      agents (bronchoprovocation and bronchodilatation). Finally, two recent promising
      applications of FOT are described: monitoring respiratory resistance during
      invasive and noninvasive mechanical ventilation, and detection of upper airway
      obstruction during sleep.

PMID- 11980290
TI  - Hypothermia in elderly patients presenting to accident & emergency during the
      onset of winter.
AB  - It is well established that the elderly population is vulnerable to hypothermia,
      leading to increased morbidity. A prospective observational study took place
      between 1 October 1999 and 31 December 1999 in a large teaching hospital Accident
      and Emergency department. Core temperature was assessed at presentation using a
      tympanic probe on patients over 65 years of age. A total of 1543 eligible
      patients attended during the study period. Complete data was available on 958
      patients. Forty-eight patients (5%) were found to be hypothermic (core
      temperature < 35 degrees Celcius). There were two peaks in hypothermic
      presentations; these corresponded to periods of cold weather. The incidence of
      hypothermia was higher in non-ambulant patients and those with co-morbidity; the
      majority of patients lived in relatively deprived areas by a postcode derived
      deprivation index. Mortality was 34% in patients hypothermic at presentation.
      Hypothermia contributes to mortality and morbidity in elderly patients; its
      incidence may be higher than previously reported.

PMID- 11980291
TI  - Tamoxifen therapy in steroid-resistant Riedels disease.
AB  - Riedels thyroiditis is a rare chronic inflammatory disorder characterised by
      extensive fibrosis of the thyroid gland and sometimes the surrounding tissues. We
      report a case of Riedels Thyroiditis in a middle aged female presenting with
      goitre, stridor and dyspnoea. She initially responded to corticosteroid treatment
      and subsequently to tamoxifen. The rationale for these treatments are discussed.

PMID- 11980292
TI  - Atypical presentation of tuberculosis meningitis: a case report.
AB  - A 19 year old woman presented with atypical symptoms of tuberculous meningitis.
      Meningitis is the most serious form of tuberculosis (TB) and it often presents
      with nonspecific signs and symptoms. Delayed diagnosis can result in rapid
      progression of neurological deficits and poor prognosis. Polymerase chain
      reaction and other nucleic acid amplification methods are becoming increasingly
      useful for the rapid detection of Mycobacterium tuberculosis in the cerebrospinal
      fluid. Early treatment reduces morbidity and mortality of this serious condition.

PMID- 11980293
TI  - Chromosome 2 reciprocal congenic strains to evaluate the effect of the genetic
      background on blood pressure.
AB  - The localisation of quantitative trait loci (QTL) is the first step towards gene
      identification. This is then verified by the construction of reciprocal congenic
      strains. The hypertensive SHRSP and normotensive WKY strains were used in a speed
      congenic approach to confirm the existence of a QTL on rat chromosome 2. Systolic
      baseline and salt loaded blood pressures were measured by radiotelemetry.
      Transfer of the chromosome 2 blood pressure QTL region from WKY into an SHRSP
      background significantly reduced blood pressure, with the increased significance
      at the salt loaded period, compared to the SHRSP. The reciprocal congenic blood
      pressure showed a significantly increased baseline systolic pressure compared to
      the WKY, with no change in significance at the salt loaded period. Thus we have
      successfully captured a gene(s) which contribute to blood pressure regulation in
      both congenic strains. This will facilitate further positional cloning of the
      causative genes first in this model and then in human essential hypertension.

PMID- 11980294
TI  - [Sacral nerve stimulation: promising treatment for anal incontinence?].

PMID- 11980295
TI  - [Nosocomial infection: a challenge to reason].

PMID- 11980296
TI  - [Laparoscopy: incisional hernias].
AB  - Post-laparoscopics incisionals hernias are among the serious complications of
      laparoscopy, however they are probably under-reported. We undertook a literature
      review to discuss their main characteristics. We emphasized on the need of
      controlled studies regarding their prevention measures.

PMID- 11980297
TI  - [Laparoscopic treatment of large hiatal hernias using a prosthesis. Report of ten
      cases].
AB  - OBJECTIVE: To evaluate prospectively the laparoscopic surgery for giant hiatal
      hernias treated by fundoplication and hiatal prosthesis. PATIENTS AND METHODS:
      Ten patients were included in this study. Surgical technic included the
      dissection of oesophageal hiatus, the sac excision and the dissection of the
      abdominal oesophagus to obtain a physiological length. The decision criterion for
      a prosthesis was the hiatus oesophagus diameter of 5 cm or more. The crura were
      closed and the hiatus was reinforce by a prosthesis of 15 x 15 cm. All patients
      underwent a fundoplication whether partial or complete. RESULTS: Eight patients
      had a type III hernia, and 2 had a type II. The mean size for the hiatus was 6.5
      cm (5.5-8). Eight patients underwent a total fundoplicature and 2 a partial one.
      The prosthesis was made of polypropylene in 5 cases. Average operating time was
      182 min (78-240). One patient had postoperative morbidity, with gastroplagia
      which resolved. There was no mortality. Mean hospitalisation duration was 7.7
      days (5-12). No one case of recurrence have been noticed after a mean follow-up
      of 24 months (8-40). CONCLUSION: It appears that the large size hiatal hernia
      (more than 5 cm) can be treated with good results by using a prosthesis during
      laparoscopic fundoplication.

PMID- 11980298
TI  - [Incidence of surgical site infection in ambulatory surgery: results of the
      INCISCO surveillance network in 1999-2000].
AB  - OBJECTIVES: To estimate the incidence of surgical-site infections (SSI) in
      ambulatory surgery and to identify risk factors based on the surveillance network
      INCISO in 1999-2000. PATIENTS AND METHODS: Annually, during a three-month period,
      each surgical ward had to include 200 consecutive operations. Patients were
      surveyed over the month following surgery. For each patient, data including peri
      operative factors, type of procedure and SSI occurrence were collected on a
      standardized form by a surgical staff committed for the study. RESULTS: Of the
      5,183 patients who underwent an ambulatory surgery, the SSI incidence ratio was
      0.4% (95% CI [0.3-0.7]). Orthopedic, gynecologic/obstetrics, head and neck, skin
      and soft tissues surgery accounted for 83% of all ambulatory procedures. 93% of
      patients belonged to the 0 risk category of the National Nosocomial Infections
      Surveillance system (NNIS) index. Emergency, age, american anesthesia risk score
      (ASA), Altemeier wound class, and procedure duration were not found to be risk
      factors for SSI in ambulatory surgery. CONCLUSION: Based on these surveillance
      data, infectious risk was low in ambulatory surgery and was not associated with
      known SSI risk factors.

PMID- 11980299
TI  - [Renal and aortic localizations in Takayasu's disease].
AB  - AIM OF THE STUDY: The aim of this work was to study the localizations of
      Takayasu's disease to the aorta and the renal arteries, the long-term results of
      their surgical treatment and the evolution of the disease with time. PATIENTS AND
      METHODS: From 1972 to 2000, 23 patients (16 females, 7 males) with aortic and/or
      renal lesions were operated on. Mean age was 19.5 +/- 12.4 years. Despite heavy
      medical treatment, all had severe and uncontrollable hypertension. Eighteen
      patients had associated lesions of the aorta and renal arteries, 5 had isolated
      lesions of the renal artery, 10 had lesions of mesenteric arteries, 6 had lesions
      of supra-aortic trunks. Percutaneous transluminal angioplasty of the renal artery
      (ies) was attempted in 4 cases and was unsuccessful in all. Due to bilateral
      lesions in 12 patients, the surgical treatment consisted of 3 nephrectomies and
      32 artery repairs of which 23 were performed by conventional in situ surgery and
      9 by extracorporeal repair. An aortic bypass was performed in 7 patients and
      revascularization of other visceral arteries in 3. The follow-up extends from 1
      to 18 years (mean: 5). RESULTS: There was no mortality. Three postoperative
      thromboses of repairs occurred: 2 of renal artery and 1 of mesenteric artery.
      Immediate results on blood pressure control were as follows: complete cure in 18
      patients (78%), improvement in 3 (13%) and failure in 2 (9%). During the follow
      up, evolution of the disease was observed in 10 patients (43%): 4 repeat stenoses
      of renal arteries due to aggravation of aortic lesions requiring reoperation in 2
      patients, 3 aggravation of aortic lesions requiring an aortic bypass in 1
      patient, 1 coronary insufficiency requiring a coronary bypass at 8.5 years.
      During the long-term follow up, due to secondary anatomical deteriorations, the
      results of surgery on blood pressure control were as follow: complete cure in 14
      patients (61%), improvement in 4 (17%), failure in 5 (22%). CONCLUSION: Surgical
      treatment of reno-aortic lesions in Takayasu's disease must be reserved to
      patients whose arterial hypertension is uncontrollable despite heavy medical
      treatment. Results are altered by the evolution of the disease either locally or
      in other territories and that may require several operations. Due to frequently
      occurring late degeneration of repairs, surgical therapy must be carefully
      decided and patients' follow-up must be prolonged.

PMID- 11980300
TI  - [Primary juvenile hyperparathyroidism. Report of 24 cases].
AB  - AIM OF THE STUDY: Primary hyperparathyroidism usually affects elderly patients.
      Juvenile primary hyperparathyroidism is rare, and raises diagnostic and
      prognostic problems. The aim of this retrospective study on 24 patients is to
      establish clinical, histological, and therapeutic features of juvenile primary
      hyperparathyroidism. PATIENTS AND METHODS: From 1986 to 2001, 673 patients were
      treated for primary hyperparathyroidism in our department. Twenty four patients
      were younger than 30 years old (3.5%). There were 14 women and 10 men. Mean age
      was 23 year (14-30). Clinical manifestations, pathologics findings and
      postoperative results were studied. RESULTS: Sixteen patients presented a
      sporadic form of primary hyperparathyroidism with a single adenoma. Clinical
      manifestations were renal symptoms in 11 cases and acute hypercalcemia syndrome
      in 2 cases. Seven patients had a NEM I syndrome: parathyroid lesions were 6
      hyperplasia and one adenoma. A 27 years old woman presented a recurrent familial
      isolated hyperparathyroidism. She was operated on 10 years before and at
      reoperation parathyroid carcinoma was found. Nineteen patients were cured after a
      post operative follow up ranging from 3 to 168 months. One patient had an
      asymptomatic hypercalcemia recurrence. Two patients presented permanent
      hypoparathyroidism treated with calcitriol and calcium. CONCLUSION: Sporadic
      forms represent majority of cases of juvenile hyperparathyroidism. Renal
      manifestations are usual. Nevertheless, multiple endocrine neoplasia type 1 has
      to be evocated.

PMID- 11980301
TI  - [Management of visceral artery aneurysms. Retrospective study of 23 cases].
AB  - STUDY AIM: To evaluate symptoms and results of the treatment of aneurysms of
      digestive arteries. PATIENTS AND METHOD: Retrospective study of 23 patients (14
      male and 9 female, mean age = 51 years) treated in two departments of academic
      hospital. We studied the aneurysms characteristics (location, number, size,
      etiology) the type of treatment, and occurrence of post-operative complications.
      RESULTS: The aneurysms involved the splenic artery in 13 patients (56%), the
      superior mesenteric artery in 5 patients (22%), the hepatic artery in 3 patients
      (13%), the gastroepiploic artery in 2 patients (9%). There were thirty-one
      aneurysms (24 true aneurysms and 7 pseudo-aneurysms) in 23 patients. Diagnosis
      was mainly done by the CT-scan. An aneurysm rupture occurred in 7 patients (30%).
      Treatment was surgery for 26 aneurysms (84%) or a radiological embolization in 3;
      abstention was decided for 2 aneurysms (6%). No death was observed. CONCLUSION:
      The bad prognosis after rupture, the lack of predictive factors of rupture
      combined with the good results of surgical treatment suggest to prefer a surgical
      treatment at first. Embolization could be reserved for the contra-indication of
      surgery and when aneurysms are poorly accessible to surgery.

PMID- 11980302
TI  - [Radiation-induced esophageal carcinoma: report of 11 cases].
AB  - STUDY AIM: Radiation-induced oesophageal carcinoma can occur several years after
      mediastinal irradiation. The aim of this study was to report 11 cases of this
      rare entity with analysis of its diagnostic, therapeutic and prognostic special
      features. PATIENTS AND METHODS: From 1983 to 2001, 10 female and one male
      patients, aged 47 to 76 years, were treated for an oesophageal squamous cell
      carcinoma which was diagnosed 5 to 25 years after mediastinal irradiation. This
      irradiation (30 to 78 Gy) was administered in 8 women for breast carcinoma and in
      other patients for lymphoma. Only one patient had alcoholic consumption and 2
      were smokers. An oesophagectomy was performed whenever possible. RESULTS: All
      (but one) oesophageal tumors were symptomatic. Ten patients underwent an
      oesophagectomy, including 2 without thoracotomy. Postoperative course was
      uneventful in 6 cases, 3 patients developed transient respiratory failure and one
      patient died postoperatively. At late follow-up, 6 patients developed distant
      metastases (mainly hepatic and pulmonary). These metastases were associated with
      mediastinal recurrences in 2 cases. No isolated mediastinal recurrence occurred.
      Median survival was 13 months. CONCLUSION: Clinical presentation and surgical
      treatment of radiation-induced oesophageal carcinoma are similar to those of
      other oesophageal squamous cell carcinomas. After oesophagectomy, isolated
      mediastinal recurrences seem to be rarer than with other cancers. These cancers,
      which are almost all symptomatic, have a poor prognosis.

PMID- 11980303
TI  - [Thyrotoxic hypokalemic periodic paralysis. Report of three cases].
AB  - AIM OF THIS STUDY: Hypokaliemic thyrotoxic periodic paralysis (HTPP) is an
      uncommon complication of hypothyroidism. Mostly described among Asian patients,
      it is rare in the other ethnic groups, in particular in caucasians people. Among
      the possible mechanisms, modification of potassic flows in relation to anomalies
      of the sodium-potassium pump were evoked. PATIENTS AND METHOD: We present the
      cases of three caucasians patients operated on for HTPP. These patients had all
      previous history of several paretic episodes. The flask paralytic attacks
      occurred in a brutal way or were preceded by diffuse myalgias. They reached the
      proximal muscles, especially in inferior limbs. No patient had any respiratory
      complications. These three patients underwent total thyroidectomy to treat the
      symptoms of HTPP. RESULTS: In the three cases, a total thyroidectomy allowed the
      recovery of the symptoms. After a four years average period of post-operative
      follow-up, no patient presented any repetition of HTPP. The hyperthyroidism is
      the cause of decompensation of the molecular anomaly. CONCLUSION: In our opinion,
      surgical treatment (total thyroidectomy) is needed in order to reduce the
      potential gravity of this pathology.

PMID- 11980304
TI  - [Hemorrhagic digestive metastases from testicular choriocarcinoma].
AB  - The metastasis of testicular choriocarcinoma are often hemorrhagic, primarily of
      cerebral or pulmonary seat. The secondary digestive localizations are rare and of
      bad forecast when they bleed. The surgical operation by laparotomy allows the
      topographic diagnosis and the treatment, but was made responsible for hemorrhagic
      decompensation of other metastatic localizations engaging the vital forecast.

PMID- 11980305
TI  - [Complicated omental splenosis].
AB  - Splenosis results from autotransplantation of splenic tissue, usually after
      traumatic splenic rupture. The diagnosis is suggested by the history and the
      presence of multiple nodules on computed tomography. Selective splenic
      scintigraphy utilising heat denatured red blood cells confirm the diagnosis.
      Treatment is usually conservative with surgical excision reserved for complicated
      cases. We report a case of splenosis associated with phlegmon and infectious
      process, requiring surgical intervention.

PMID- 11980306
TI  - [Intracardial migration of a bullet: diagnosis and management].
AB  - Venous pellet embolism to the cardia after shotgun wound is a very rare
      occurrence. Number and size of pellets, at the impact make this migration easier;
      embolism is asymptomatic and may occur 15 years after the injury. Many problems
      must be mentioned: mechanics of entry into the heart (own velocity, venous flow),
      topographic diagnosis (chest X-ray, transthoracic, transoesophageal ultrasound
      and CT-scan), local outcomes of this projectile (local erosion, clot,
      endocarditis), destination of a new migration (pulmonary embolism, left heart),
      indications of extraction, supervision. Extraction musn't be systematic, but only
      in the event of a patent foramen ovale with a risk of systemic embolism, which
      clinical outcomes are most serious or in the event of complications. The authors
      report on a 22 years old patient observation whose treatment was abstention and
      supervision.

PMID- 11980307
TI  - [The "pneumoneck" in videocervicoscopy: operative technique and anatomic limits].
AB  - The aim of this study was to describe a technic in order to create a gas space
      "pneumoneck" during videoendoscopic surgery of the neck and to determine the
      anatomical limits of this space. Data were based on a surgical experience and on
      the dissection of two corpses. This space was located between the two layers of
      the pre-tracheal lamina of the cervical fascia. This space was enclosed and
      favourable to detachment with insufflated gas without subcutaneous emphysema.
      This approach can be used for parathyroid and thyroid surgery.

PMID- 11980308
TI  - [Sleep disorders. Fifth international meeting on sleep disorders, Bordeaux, April
      12-13 2001].

PMID- 11980309
TI  - [Sleep. Sleep Odyssey, Punta del Este, Uruguay, October 2001].

PMID- 11980310
TI  - [Colchicine and Behcet's disease: an efficacious treatment finally recognized!].

PMID- 11980311
TI  - [Antiphospholipid syndrome with only antiphosphatidylethanolamine antibodies:
      report of 20 cases].
AB  - PURPOSE: The association of antiphosphatidylethanolamine antibodies (aPE) as the
      only antiphospholipid antibody with antiphospholipid syndrome (APS) is discussed.
      The aPE was described as the sole antibody in many cases suggesting APS. aPE was
      not included in the Sapporo criteria for the classification of APS. METHODS: We
      investigated the clinical features of 20 patients with aPE only; 17 patients had
      symptoms potentially related to APS (group 1) and three had other manifestations
      (group 2). RESULTS: There were 15 women and five men, mean age was 35 +/- 12
      years at the beginning. In group 1 (n = 17), ten patients presented arterial
      thrombosis, nine venous thrombosis (five had both), and six microvascular
      thrombosis (livedo reticularis, lacunar pathology). The aPE positivity was
      persistent in 13 patients. A subgroup of four patients (three women) presented
      arteriosclerosis with peripheral arteriopathy which started before 45 years of
      age. They had another atherosclerosis risk factor associated with aPE
      persistence. In group 2 (n = 3), there was no thrombotic event, one demyelinating
      pathology, one microvascular pathology, and one arterial dysplasia. The aPE
      positivity was never confirmed. Finally, 13 patients presented an APS with aPE
      only, confirmed at least 8 weeks later. CONCLUSIONS: Our study points out that
      testing for aPE would be of interest for patients when symptoms were potentially
      related to APS, particularly when other antiphospholipid antibodies were
      negative. This description questions the enlargement of the APS biological
      criteria defined in Sapporo. The role of aPE in atherosclerosis is considered.

PMID- 11980312
TI  - [Diagnostic value of classical neurophysiologic profile in various phenotypes of
      hereditary, pressure-sensitive neuropathies].
AB  - PURPOSE: We looked for electrodiagnostic features that raise suspicion of
      hereditary neuropathy with liability to pressure palsies (HNPP). METHOD: A
      retrospective review of eight cases with confirmed histologic (one case) or
      chromosome 17 deletion (seven cases) analysis was performed. RESULTS: Autosomal
      dominant disease was present in 63% of the patients, 75% being men. Mean age at
      examination and at first symptom was 27 and 22 years respectively. Five patients
      have one or more acute nerve palsies, without residual deficit, but one presented
      sensory symptoms in internal saphena territory. Three patients had others
      phenotypes: a man presented with four episodes of facial palsy and one woman was
      asymptomatic; another patient with diabetes mellitus presented an associated
      chronic sensorimotor polyneuropathy. In agreement with other studies of HNPP we
      found in most patients a diffuse increase in distal motor latence, contrasting
      with normal or moderately decreased motor nerve conduction velocity, multiple
      electrophysiologic entrapment and diffuse reduction in sensory nerve action
      potential and/or velocity. However, this electrophysiological pattern was
      incomplete or masked in HNPP with cranial nerves palsies, in asymptomatic form of
      HNPP or in HNPP associated with polyneuropathy. CONCLUSION: These data confirm
      the clinical phenotypic heterogeneity of the 17p11.2 deletion and highlight the
      limits of the classic electrophysiological pattern in asymptomatic HNPP or
      associated with uncommon clinical features.

PMID- 11980313
TI  - [Molecular markers in the epidemiologic study of Legionella pneumophila
      infections].
AB  - PURPOSE: Legionnaires' disease is due to the inhalation of contaminated aerosols.
      The identification of the source of contamination in the aquatic environment is
      necessary to prevent the occurrence of new cases. A comparative study of clinical
      and environmental isolates is the basis of epidemiological investigations.
      CURRENT KNOWLEDGE AND KEY POINTS: Genotypic methods are now mainly used to
      compare bacterial strains. Some of these methods are based on the electrophoretic
      separation of DNA restriction fragments. When electrophoretic profile are
      complex, some fragments can be visualized after hybridization (ribotyping). Large
      sized fragments can be separated by pulsed-field gel electrophoresis. Other
      techniques are based on gene amplification, such as AP-PCR. This technique is
      easy to perform but its discriminatory power and reproducibility are lower. Some
      procedures are combining enzymatic cleavage and gene amplification. Finally
      methods based on the nucleotide sequence analysis of some genes are being
      evaluated. FUTURE PROSPECTS AND PROJECTS: Techniques enabling the rapid
      comparison of various Legionella isolates will permit a quick detection of
      outbreaks and contribute to the identification of the source of contamination.

PMID- 11980314
TI  - [Rheumatologic manifestations of Lyme borreliosis].
AB  - PURPOSE: Lyme borreliosis is a multisystemic infection caused by the spirochaete
      Borrelia burgdorferi. In European endemic areas like northeast France, articular
      manifestations are, after neuroborreliosis, the most frequent extra-cutaneous
      features observed. Among the pathogenic species of Borrelia, Borrelia burgdorferi
      sensu stricto is the most frequently identified during Lyme arthritis, but others
      species also seem to be involved. CURRENT KNOWLEDGE AND KEY POINTS: The diagnosis
      of Lyme arthritis is usually based on combined clinical data and serological
      laboratory tests. In atypical forms, detection of bacterial DNA could be useful.
      While mechanisms involved in acute Lyme arthritis are beginning to be better
      understood, the pathogenesis of chronic arthritis, which concerns about 10% of
      the patients, remains unknown. Two hypotheses are proposed to explain the
      prolonged evolution of the articular disease: a chronic persistence of Borrelia
      burgdorferi, which evades the host immune system within the joint and/or an
      autoimmune mechanism by molecular mimicry. The antibiotic therapy is codified in
      acute arthritis, but is not really adapted in chronic Lyme arthritis or post-Lyme
      syndrome. FUTURE PROSPECTS AND PROJECTS: To prevent the disease, the vaccine
      available in the United States does not offer complete protection and is not
      useful in Europe since the species heterogeneity is important for the outer
      surface protein A. A better understanding of Lyme disease pathogenesis can
      subsequently lead to new therapeutic or preventive approaches.

PMID- 11980315
TI  - [Delayed diagnosis of neurocysticercosis: two case reports].
AB  - INTRODUCTION: Neurocysticercosis is the most frequently encountered cerebral
      parasitic infection worldwide. It is due to infection of the central nervous
      system by Taenia solium larval form. According to the location of the cysts,
      parenchymal and extra-parenchymal forms may be identified, with different
      clinical expressions. EXEGESIS: We report two cases of neurocysticercosis, one
      with typical parenchymal involvement and the second with extra-parenchymal
      involvement revealed by increased intra-cranial pressure. In both cases, the
      diagnosis was established over 10 years after the onset of symptoms. CONCLUSION:
      Neurocysticercosis is very frequent in non-Islamic developing countries, and its
      incidence is increasing in industrialized nations in relation to tourism and
      immigration from highly endemic areas. Symptoms usually appear several years
      after infection and this accounts for the frequent delays before the diagnosis is
      established.

PMID- 11980316
TI  - [Two cases of polyarteritis nodosa with a good prognosis?].
AB  - INTRODUCTION: Polyarteritis nodosa is a systemic necrotizing vasculitis that may
      become serious, even with no usual poor prognosis factors. EXEGESIS: We report
      two cases of polyarteritis nodosa with negative histology, starting only with an
      extensive necrosis of the extremities. The treatment, associating corticosteroids
      and, secondarily, immunosuppressors, did not prevent a bilateral half-leg
      amputation for the two patients. In the first case the disease stabilized, but in
      the second one, it worsened, leading to death within 2 years. CONCLUSION: This
      clinical aspect of the disease is unusual and should be identified because of its
      bad prognosis. It might benefit from a treatment from the outset associating
      corticosteroids and immunosuppressors, even with no usual bad prognosis factors.

PMID- 11980317
TI  - [Acute erythermalgia: look for mushrooms!].
AB  - INTRODUCTION: To describe the first European observation of erythromelalgia due
      to mushroom poisoning. EXEGESIS: Seven cases observed and followed over 4 years
      are reported. All ill patients had eaten the same mushroom species, gathered in
      the same French alpine valley. Clinical features of erythromelalgia were
      observed. This syndrome was first described in Japan after Clitocybe acromelalga
      ingestion. It had never been observed in Europe before. Clitocybe acromelalga
      does not grow in Europe. Clitocybe amoenolens was identified as the possible
      cause of poisoning in our cases. This species can be confused with an edible
      mushroom, Lepista inversa. CONCLUSIONS: Even in Europe, recent mushroom poisoning
      is a possible cause of erythromelalgia.

PMID- 11980318
TI  - [An unusual meningeal inflammatory process].

PMID- 11980319
TI  - [A case of lymphocytic meningitis revealing a neurocysticercosis].

PMID- 11980320
TI  - [Myasthenia associated with systemic scleroderma].

PMID- 11980321
TI  - [Bilateral panuveitis and viral lymphocytic meningitis. A case report].

PMID- 11980322
TI  - [The death of drug safety and compliance?].

PMID- 11980323
TI  - [Interactions between acetylsalicylic acid and cyclooxygenase inhibitors].

PMID- 11980324
TI  - [Oral cephalosporins. Relationship between structure, pharmacokinetics and
      action].

PMID- 11980325
TI  - [Partial hearing loss in the elderly].

PMID- 11980326
TI  - [Antiallergic agents. Treatment of allergic rhinitis and conjunctivitis].

PMID- 11980327
TI  - [Methods of studying T-lymphocyte repertoires].

PMID- 11980328
TI  - [Radioactive iodine and thyroid tumors].

PMID- 11980329
TI  - [Importance of a cefpirome-vancomycin combination on bactericidal kinetics in
      severe MRSA infections in intensive care].
AB  - Vancomycin is always the drug of choice for treatment of infections caused by
      methicillin-resistant Staphylococcus aureus (MRSA) in spite of his bactericidal
      kinetic. BACKGROUND: The aim of this study was to evaluate in vivo the
      improvement of bactericidal kinetic of vancomycin associated with cefpirome
      against MRSA infection in critically ill patients. METHODS: The prospective cross
      over study was carried out in 20 patients with severe pneumonia or bacteremia.
      There were randomized to receive vancomycin 2 g per day (Group 1, n = 10) or
      vancomycin with cefpirome 2 g x 2 (Group 2, n = 10). Clinical recovery,
      bacteriologic parameters (bactericidal kinetic and bactericidal power in vivo at
      the peak and the valley), duration of ventilation and stay in ICU were
      comparatively explored in both groups. RESULTS: Clinical outcome did not
      significantly differ between Group 1 and 2. Bactericidal kinetics were better in
      the Group 2 (40% vs 60% after 6 hours to the dilution for 1/8e) but the
      difference was not significant. However, bactericidal power in sera was also
      better in the Group 2 with more bactericidal dilution at 1/16e (68% vs 88.8%: NS)
      and overall at 1/32e (10.5% vs 50%: p < 0.05) and CRP, an inflammatory marker,
      was significantly lower in the Group 2 than in the Group 1 (119.5 +/- 24 mg/l vs
      198.6 +/- 78 mg/l: p < 0.05) on the third day.

PMID- 11980330
TI  - [Therapeutic impact of streptococcal and enterococcal bacteremia in hematology
      patients].
AB  - From January 1999 to May 2000 (17 months), 21 strains of streptococci and four
      strains of enterococci have been isolated from 74 blood cultures in 25 infectious
      episodes in hematologic patients. They concerned 21 patients, of 21 to 77 years
      old. These patients suffered from acute leukaemia (14 cases), chronic lymphoid
      leukaemia (two cases), non-Hodgkin's lymphoma (two cases) or myeloma (three
      cases). Seventeen patients displayed a single streptococcal or enterococcal
      episode, two had two episodes in the course of a single stay in the hospital, two
      others in the course of two different stays. During 16 episodes (64%), the
      bacteremia occurred within 15 days after the onset of neutropenia consecutive to
      antimitotic chemotherapy, and in nine episodes (36%) it has occurred after a
      period exceeding 15 days. In six cases the patients had already received
      antibiotics with a large antibacterial activity (beta-lactam, fluoroquinolone
      and/or glycopeptide +/- aminoside) and in four cases a single antibiotic
      (synergistine or cotrimoxazole). Most streptococci (20/21) were oral streptococci
      (ten Streptococcus mitis, five S. oralis, two S. sanguis, three S. pneumoniae). A
      single strain of beta-hemolytic streptococci has been identified as S.
      dysgalactiae subsp. equisimilis. The enterococci were one strain of Enterococcus
      faecalis and three E. faecium. Ten streptococci were susceptible to 0.25 mg/L of
      penicillin G, ten were less susceptible (0.5 < or = MIC < 32 mg/L), and a strain
      was resistant (MIC = 32 mg/L). Eighteen strains were susceptible to amoxicillin
      and cefotaxime. For three strains, the MICs of amoxicillin and cefotaxime (8-16
      mg/L and 8-32 mg/L, respectively) were higher. Levels of resistance of the
      enterococci to the beta-lactam (penicillin, amoxicillin, and piperacillin) were
      variable. All species were susceptible to glycopeptides. Three patients were
      transferred in intensive care unit for respiratory distress or shock syndrome.
      Their evolution has remained severe under antibiotherapy comprising beta-lactam
      or vancomycin associated with an aminoside. This results demonstrate the interest
      of species identification to adapt the antibiotic treatment and confirms the
      frequency of oral streptococci in severe bacteremia in neutropenic patients.

PMID- 11980331
TI  - [The Pneumococcal Observatory for the Central Region, 1 April 1999 to 31 March
      2000].
AB  - Seven hundred and ninety six strains of pneumococcus were collected in the Centre
      region, from 15 laboratories, between 1st April 1999 and 31st of March 2000. Data
      were processed, using 4th dimension software, and concerned age, file number,
      consultation/hospitalisation, sample type, susceptibility to oxacillin (5
      micrograms), results of the E-test for benzylpenicillin, amoxicillin, cefotaxime
      and results of the routine disc diffusion test. Strains with reduced
      susceptibility to benzylpenicillin (PRSP) were collected by the co-ordinating
      centre to perform MICs by the reference agar dilution test and serotyping. Out of
      796 strains, 450 strains (56.7%) were categorised as PRSP and 400 of them were
      studied by the co-ordinating centre. Forty two percent of the samples originated
      from lungs, followed by 19.5% from blood samples, 15% from ear pus (85.7% PRSP)
      and 2.5% from CSF. Thirty nine percent of the patients were female. 36.6% were
      children under sixteen (70.1% PRSP) and 62.4% were adults (49.2% PRSP). Out of
      400 PRSP 106 (26.5%) were characterised as resistant and 294 (73.5%) as
      intermediate to benzylpenicillin. Compared to the agar dilution test, 90% of the
      PRSP studied by E-test had a MIC value for benzylpenicillin within +/- 1
      dilution. Thirty six strains of PRSP were resistant to amoxicillin (9% of the
      PRSP) and 10 (2.5% of the PRSP) to cefotaxime. Serotyping was done on 375
      strains. The serotypes encountered were the following: 23 (26.9%), 14 (22.1%), 19
      (19.5%), 6 (12.8%), 9 (9.9%) and 15 (5.1%).

PMID- 11980332
TI  - [In vivo sensitivity of Plasmodium falciparum to amino-4-quinolines and
      sulfadoxine pyrimethamine in Agou (Ivory Coast)].
AB  - A comparative study of the in vivo sensitivity of Plasmodium falciparum to
      amodiaquine versus chloroquine has been made among children in Agou (south Cote
      d'Ivoire). In case of resistance to these drugs, the association of sulfadoxine
      pyrimethamine was administered and followed by a J14 checking. We have noticed:
      (1) 8.47% of amodiaquine resistance versus 36.96% of chloroquine resistance (all
      these resistances are from type II), (2) a good clinical efficiency of the 4
      amino quinolines. Only 1.69% of the subjects having resistant stocks to
      amodiaquine have gone feverish down to J7 whereas 10.47% of subjects have
      clinically resisted to chloroquine, (3) a good tolerance of drugs and an
      excellent clinical and parasitological efficiency of the second intention
      treatment. These data are in favour of using first the 4 amino quinolines
      (particularly the amodiaquine) in the treatment of simple bout of malaria to
      Plasmodium falciparum in this region. In case of resistance to these drugs, we
      recommend the combination sulfadoxine-pyrimethamine.

PMID- 11980333
TI  - [Bioactive films for biomaterial coating and intended for tissue engineering: new
      original methods?].
AB  - Numerous functionalized biomaterials aimed to induce specific cellular or
      tissular responses have been developed in the last decade. They result often from
      a specific treatment of the interface of the material. Techniques like
      physisorption, covalent binding or deposition of a Langmuir-Blodgett film have
      been employed to modify surface properties. We describe here a novel approach
      based upon an alternated adsorption of polyelectrolytes (polyanions or
      polycations) leading to the build-up of a film. These films can be functionalized
      through protein insertion (ligands) or by covalent peptide bindings able to
      interact with cellular receptors. Combined with a high affinity for calcium or
      phosphate complexing properties such functionalized architectures could
      constitute an original way to favour osseointegration.

PMID- 11980334
TI  - [Mineralization of the dental pulp: contributions of tissue engineering to
      tomorrow's therapeutics in odontology].
AB  - When bioactive molecules such as bone sialoprotein (BSP), bone morphogenetic
      protein-7 (BMP-7, also termed OP-1) and chondrogenic Inducing Agents (CIA, A+4
      and A-4) were implanted in the pulp of the first upper molars, mineralizations
      were induced. They were either limited to the formation of a reparative dentinal
      bridge closing the pulpal wound (CIA A+4), or filled the mesial part of the
      coronal pulp (BSP), or filled totally the pulp located in the root canal (BMP-7
      and CIA A-4). Consequently, these molecules may change in the next future the
      every day practice in dentistry.

PMID- 11980335
TI  - [The Rel/NF-kappa-B transcription factors: complex role in cell regulation].
AB  - The transcription factor NF-kappa B has attracted widespread attention among
      researchers. NF-kappa B displays some original characteristics including rapid
      regulation, the wide range of genes that it controls and its probable involvement
      in several diseases. In resting cells, NF-kappa B is kept in an inactive form in
      the cytoplasm where it is bound to a member of the I kappa B family of inhibitory
      proteins. NF-kappa B can be activated by exposure of cells to physiological as
      well as non physiological stimuli. Upon cell activation, the inhibitors are
      modified through site specific phosphorylations which target them for subsequent
      ubiquitination and proteolytic degradation by the proteasome. Removal of the
      inhibitor unmasks the nuclear localization signals on subunits of NF-kappa B.
      Free NF-kappa B moves to the nucleus where it binds to target DNA elements and
      activate transcription of genes encoding proteins involved in immune responses,
      inflammation or cell proliferation. NF-kappa B could be considered as a co
      ordinating element in the body's responses to situations of stress, infection or
      inflammation. A tight regulation of NF-kappa B seems to be crucial since a
      dysfunction could promote pathogenic processes including AIDS (acquired
      immunodeficiency syndrome), rheumatoid arthritis and cancer. Additionally, it
      will be important to understand the exact roles for NF-kappa B in regulating
      apoptosis. NF-kappa B is now regarded as a good therapeutic target and the
      development of specific inhibitors should lead in the next future to novel
      therapeutics.

PMID- 11980336
TI  - [Role of intracellular zinc in programmed cell death].
AB  - Apoptosis is a type of cell death involved in several biological events during
      tissue development, remodelling or involution. It could be induced by several
      extracellular or intracellular stimuli with an important role for metals like
      zinc or calcium. Cellular zinc is described as an inhibitor of apoptosis, while
      its depletion induces death in many cell lines. Using different chemical tools
      like specific zinc-chelators or ionophores, it is possible to study and
      understand the mechanisms of programmed cell death induction. The decrease in
      intracellular zinc concentration induces a characteristic apoptosis with
      apoptotic bodies formation and nuclear DNA condensation and fragmentation. This
      zinc depletion activates the caspases-3, -8 and -9, responsible for the
      proteolysis of several target proteins like poly(ADP-ribose) polymerase or
      transcription factors. Zinc addition in cell culture medium prevents the
      apparition of morphological and biochemical signs induced by intracellular zinc
      chelation, but also by other apoptosis inducers like etoposide or tumour necrosis
      factor alpha (TNF alpha). However, excess of zinc can also be cytotoxic. The
      balance between life and cell death is maintained by several zinc channels,
      controlling the intracellular zinc movements and the free amount of the metal.

PMID- 11980337
TI  - [The posterior interosseous flap in the child: 13 case reports].
AB  - INTRODUCTION: The posterior interosseous flap is used to cover skin defects in
      the hand, wrist, forearm and elbow. It is currently, commonly indicated for
      adults, but it may be used for child too. MATERIALS AND METHOD: Twelve children
      underwent a posterior interosseus flap (13 flaps). Their ages ranged from 3 to
      17.5 years with a mean of 6.5 years. There were seven boys and five girls. The
      flaps were used to treat different type of lesions: the most frequent etiology
      was burn injuries or sequels (nine patients), there were one extravasation of
      anticarcinogenic agent, one syndactyly and one arthrogryposis. The localizations
      of the skin loss were the first web space (six patients), the dorsal hand (five
      patients) and the elbow (two patients). RESULTS: The average of the operation was
      eighty minutes. The survival of the flaps was excellent. Only one flap had a
      partial necrosis. CONCLUSION: Posterior interosseus flap may be used in coverage
      of children's limb. The diameter of the vessels is not a difficulty in the flap
      dissection. As the adults, the viability of the flap is excellent and allows to
      cover most of the skin defect of the dorsal hand or elbow.

PMID- 11980338
TI  - [Piso-triquetral osteoarthritis. Thirteen case reports and review of the
      literature].
AB  - Piso-triquetral osteoarthritis (OA) is an infrequent cause of ulnar wrist
      compartment pain. Specific clinical manoeuvres may help for diagnosis. If this
      aetiology is suspected, a 30 degrees oblique wrist X-ray in supination and
      sometimes a CT scan with transverse cuts should be performed demonstrating a
      joint narrowing and osteophytes formation. The FCU-pisiform biomechanical unit
      transfers the wrist flexion forces. A series of 13 cases of piso-triquetral OA is
      presented in 12 patients (six females and six men) treated between 1990 and 1997.
      Mean age was 52.7 y. Pain at resisted motion in flexion and ulnar deviation and
      strength decrease was always present at clinical examination. Subperiosteal
      pisiform excision has been constantly performed. Continuity of FCU insertions and
      its distal ligamentous extensions has been preserved. Mean F-up was 18.1 months
      (3-57). Pain has disappeared in seven cases and significantly decreased in five.
      NSD was present in one case. Range of motion and strength was normal in all
      cases. Ulnar nerve paresthesias has always disappeared. The pisiform bone is not
      a sesamoid: a true joint with the triquetrum exists. From the phylogenetic point
      of view, three theories have been proposed: (a) in some species, pisiform is
      fused with adjacent bones or metacarpals; (b) pisiform is a remnant of a
      polydactyly hand; (c) pisiform is a remnant of the carpal central row.

PMID- 11980339
TI  - Open reduction and internal fixation of un-united fractures of the distal radius:
      does the size of the distal fragment affect the result?
AB  - Two cohort populations consisting of 13 patients with an un-united fracture of
      the distal radius in whom the distal fragment had more than 5 mm of subchondral
      bone supporting the articular surface distal to the site of the nonunion and ten
      patients with an un-united fracture of the distal radius with a smaller distal
      fragment were compared. There were no preoperative differences with respect to
      age, gender, interval between injury and index procedure, preoperative amount of
      radius tilt, ulnar inclination and ulnar variance, or the preoperative function.
      Independent of the size of the distal fragment in all patients the distal radius
      was restored to gain bony union and realignment with preservation of some wrist
      motion. The length of the follow-up period averaged 30 months for the small
      fragment group compared with 22 months for the large fragment group. Bony union
      was achieved in 22 patients. One patient out of the large fragment group failed
      to heal the fracture and had wrist fusion. At the follow-up examination there
      were no significant differences in the radiological and clinical outcome between
      the two groups. No differences were seen on total range of motion of forearm
      supination and pronation with an average of 135 degrees in the large fragment
      group and 145 degrees in the small fragment group. Wrist motion revealed no
      significant differences in the flexion-extension arc, averaging 90 degrees in the
      large fragment group and 83 degrees in the small fragment group. Total range of
      motion of radial and ulnar deviation of the wrist was similar, averaging 39
      degrees in the large fragment group and 43 degrees in the small fragment group.
      Grip strength averaged 59% compared with the opposite limb for the large fragment
      group and 67% for the small fragment group. We believe that the results of
      reconstruction of un-united fractures of the distal end of the radius for
      patients in whom the distal fragment had less than 5 mm of subchondral bone
      supporting the articular surface distal to the site of the nonunion are
      comparable to the results for patients with a larger distal fragment. Therefore,
      we believe that surgeons should try to preserve even a small amount of wrist
      motion and reserve wrist fusion as a final resort.

PMID- 11980340
TI  - [Reorientation osteotomy of the trapezial saddle].
AB  - At its early stage, the thumb TM osteo-arthritis is occasionally painful during
      some activities and there are mainly radiological signs, only visible on specific
      views and with maximum amplitudes. They are the first metacarpal base imperfect
      reintegration in the trapezium saddle in ante-position and an increased slope
      angle of 140 degrees. So, the "slippery saddle" of the trapezium induces a
      metacarpal base subluxation. The goal of the proposed technique is to correct the
      orientation of the trapezial saddle. The slope angle must return to its normal
      value of about 125 degrees, thanks to an opening wedge osteotomy into the
      trapezium, completed with a bony wedge insertion. Proposed for the first time in
      1983, and used only once by Dr. Heim, this technique was "rediscovered" recently
      and used on five patients in ten years. It is easy to do, the only complication
      being two post-operative radial nerve sensitive branch neuromas. In six cases on
      seven, the pain disappeared, even if the osteo-arthritis was evolving for the two
      former cases. The functional recovery was total and the patients were satisfied
      in most of the cases. In spite of this short series, this technique is worth
      being used for the early stage of thumb osteo-arthritis, eventually combined with
      others techniques like tenotomy of the Abductor pollicis longus accessories or
      different types of ligamentoplasties. It is, in any case, more logical than the
      first metacarpal osteotomy.

PMID- 11980341
TI  - [Role of external fixators for treatment of humeral fractures: report of 23 cases
      using Orthofix fixators].
AB  - From 1991 to 1998, 23 humeral fractures has been treated using the Orthofix
      external fixator. Average age of the patient was 42 y and average follow-up 55.5
      m. Initial trauma was: 13 traffic accidents, four falls at home, two devastating
      farming accidents, two sports accidents, one aggression and one gun accident. AO
      classification was used and location of the fracture was classified using
      Hackethal classification modified by de la Caffiniere. Majority of fractures were
      located at the one-third distal humerus and the majority was also comminuted. At
      follow-up, elbow range of motion was 130 degrees, shoulder range of motion 161
      degrees, external rotation 69.5 degrees and internal rotation 92.5 degrees. Using
      the classification of Stewart and Hundley, eight excellent, seven good, three
      fair and two bad results were obtained. There were no postoperative radial nerve
      palsy. Two external fixators had to be removed because of pin mobility. Failures
      were: non union and pin mobility in one patient which has to be reoperated on;
      two non unions have been grafted on and plated. There were no malunion in the
      postoperative X-rays. This device is our favourite for this type of injury
      because of its rigidity and the possibility of secondary dynamization. The
      external fixator was removed after union: this explains the long delay of union
      in our series.

PMID- 11980342
TI  - Subperiosteal osteoid osteoma of the triquetrum mimicking an avascular necrosis.

PMID- 11980343
TI  - [Volar transcaphocapitate perilunate disclocation of the carpus: a new variety, a
      new approach].
AB  - On the one hand, surgical treatment of dorsal perilunate fracture-dislocation is
      now well codified. The posterior approach is preferred by the majority of the
      authors. On the other hand, surgical schedule for volar perilunate dislocation is
      not well establish in the literature. The anterior approach is the most
      frequently recommended. In case of Fenton's syndrome (scaphocapitate fracture),
      the head of the capitatum is described with a rotation of 180 degrees. The
      authors reports a case of a volar transcaphocapitate perilunate fracture
      dislocation of the carpus in a polytrauma. The head of the capitatum was in place
      onto the neck. By a posterior approach, a primary repair of all the elements has
      been performed including open reduction and internal fixation of the carpal
      scaphoid fracture in addition with a bone graft. The capitatum were fixed by
      wiring. At two years follow-up, the result were good. The patient did return at
      the same work. Clinically, there was a range of motion of 70 degrees in flexion
      extension. Radiologically, all the fractures healed and there were no intracarpal
      desaxation. Volar perilunate fracture-dislocation of the carpus and Fenton's
      fracture (scaphocapitate fracture) are two exceptional entities in the
      literature. Association of both lesions has been found only twice in the
      literature. No similar case with a head of the capitatum in place has been
      already described.

PMID- 11980344
TI  - [Radio-carpal palmar subluxation: treatment by volar rim osteotomy of the
      radius].
AB  - A case of post-traumatic carpal proximal instability which was surgically treated
      two months after the initial trauma is reported. A 41 years old man presented a
      volar subluxation of the scaphoid associated with a fracture of the volar rim of
      the distal radius and an increased scapho-lunate gap. This subluxation was
      initially missed because of the discretion of the radiographic signs and was
      confirmed by CT scan. A volar rim osteotomy with bone grafting was performed for
      a buttress support which allowed the reduction of the volar subluxation of the
      external part of the carpus. Fourteen months after the operation radiographs
      showed the effectiveness of the butress support for the treatment of proximal
      carpal instability, but also arthritic changes in the proximal part of the
      scaphoid.

PMID- 11980345
TI  - [The right to the title of hand surgeon].

PMID- 11980346
TI  - Congenital malformations of the hand and forearm.

PMID- 11980347
TI  - [Prevalance of nosocomial infections in tetraplegic upper extremity surgery.
      Prospective study of twenty patients].
AB  - INTRODUCTION: Many risk factors of nosocomial infection may be met with
      tetraplegic patients. The objective of this work was to study the prevalence of
      colonization by 3 multiresistants bacteria (methicillin resistant staphylococcus
      aureus (MRSA), Klebsiella pneumoniae with widened spectrum beta lactamase or
      multi-resistant Acinetobacter baumannii) on this population. MATERIAL AND
      METHODS: It was about a prospective study for which we included 20 consecutive
      patients coming from a rehabilitation of long stay center to have a surgical
      operation of palliative reanimation of the upper limb. For each patient, the
      first morning of his hospitalization, many sites cultures were carried out for
      bacteriological analysis whose results were returned in 48 h to the operator. No
      patient was excluded. RESULTS: Five patients (25%) showed the presence of SARM.
      One patient (5%) showed the presence of Klebsiela pneumoniae. One of the patients
      carrying a SARM was also carrying Acinetobacter baumannii. Overall 6 patients
      were contaminated (30%) but no postoperative infection occurred, neither at the
      time of the hospitalization nor after the exit of the service. DISCUSSION: The
      various risk factors of nosocomial infection appearance met in tetraplegic
      patient were analyzed. This study showed that the cares of tetraplegic patients
      limited to the maximum the risk of nosocomial infection appearance (no one in
      this series) in spite of an important contamination met in this type of
      population which presents long durations of hospitalization, main risk factor
      regularly met.

PMID- 11980348
TI  - [Injuries of the first web. Surgical indications].
AB  - Treatment of the first web injuries are based on the concept of one stage repair
      of the complex injuries of the hand with early motion. Radical debridement is
      specially important in case of muscular attrition. Fasciotomie of the first web
      is systematic in case of crush injuries for avoiding compartimental syndrome. For
      prevention of first web retraction, one or two Kirchner wires are placed in
      emergency between first and second metacarpal, and later a spilt in maximal anti
      position of the first ray. In case of communited fractures, skeletal
      stabilisation use inlay internal devices, such the blocked intramedullary nail.
      First web reconstruction must take into consideration the cutaneous functionnal
      units of the hand, described by Michon. Thin and split-thickness grafts are
      rarely used for covering skin defects of the first web space, because their
      ability of retraction. Exposition of bone or tendons leads to the realisation of
      a flap. Soft tissue coverage must be achieved in emergency or after a second look
      within the first 48 hours. The kite flap is the most useful local flap for the
      first web space. The interosseous flap is the best choice among the regional
      pedicled flap. The use of the Chinese flap must be very careful, because the
      possibility of contusion of the radial pedicle in these types of injuries. It is
      only in case of contra-indication of the interosseous flap that free flaps can be
      realised, as the lateral arm flap or the parascapular flap. The groin flap keeps
      few indications for aesthetic reasons, or when regional flaps and microsurgery
      are contra-indicated.

PMID- 11980349
TI  - [Psychological approach to congenital hand deformities. Congenital deformities,
      the desire to know].
AB  - The psychological approach to congenital malformation is determined by the stares
      of the others and the individual's needs. The relationship of the body of the
      person afflicted with a congenital malformation is a question of aesthetic
      suffering and not of functional use. Caught up in a network of a priori and
      anxiety-based projections, it is difficult for patients, children, adolescents or
      adults, to express themselves and make themselves heard. This multi-faced issue
      poses a basic problem for a society, which penalizes physical deformity. Beyond
      the medical techniques, the subject's ethic has to be considered.

PMID- 11980350
TI  - [Constitutional anomalies of the terminal branches of the brachial plexus in the
      axial and brachial regions. Results of 42 cases and review of the literature].
AB  - The authors report anatomical variations of the terminal brachial plexus branches
      in 42 cadaveric dissections. The results are compared with results reported in
      literature which revealed a new variation: ulnar nerve originating in posterior
      beam. This study demonstrates that there exist not one but several brachial
      plexes which could have potential clinical implications.

PMID- 11980351
TI  - [Nerve entrapment syndrome of the elbow and forearm].
AB  - In this study we will discuss entrapment of the median, ulnair, radial and
      lateral antebrachial nerves of the elbow and the forearm. Compression of the
      nerves may occur when they traverse a tunnel and an incompatibility exists
      between the diameter of the tunnel and its contents (e.g. nerves, tendons,...).
      However, at the elbow and the forearm the nerves are also exposed to particularly
      dynamic compressions. This is due to anatomical relationships changing between
      the nerve and its surrounding muscles, tendons and aponevroses during the motion
      of flexion-extension of the elbow and the prono-supination of the forearm. The
      possibility of this dynamic factor should be thoroughly explored during the
      examination through appropriate dynamic tests as described in this study.

PMID- 11980352
TI  - [Secondary treatment of digital mutilations: reconstruction or amputation].
AB  - Decision for stump improvement, shortening or reconstruction after finger
      mutilation is based on multiple factors. Some of them belong to the patient, age,
      psychological background, job and leisure activities and cosmetic expectation.
      Others belong to the injury, its mechanism and the anatomical lesions.
      Abstention, prostheses and rehabilitation are among the options. Conventional
      techniques are not to be forgotten as age remains an ultimate frontier in
      microsurgical reconstruction to obtain a good sensory result. Function and
      appearance are closely linked for a useful and a used hand.

PMID- 11980353
TI  - [Thumb arthritis yesterday and today. Epidemiologic comparison in an ancient
      population].
AB  - The aim of the study was to assess the rate of thumb osteoarthritis in an ancient
      population (before the industrial revolution) according to the age, the sex and
      the side affected, and to compare the results to the current epidemiologic data.
      This study was performed in bones from the convent graveyard of the Soeurs Grises
      de Beauvais (15th to 18th century). The rate of thumb osteoarthritis was assessed
      in 73 adult individuals (34 men and 39 women) divided into 2 age groups: 35-49
      and over 50. The rates of thumb osteoarthritis in each group were compared
      according to different factors (age, sex, side affected). The statistical study
      showed a higher rate of thumb osteoarthritis in elder people in general, and in
      male but not in female individuals. The rate of bilateral thumb osteoarthritis
      was higher in women. However, no difference was found between both sides of human
      body whatever the age or sex. As for the female population, the results were
      identical those of the current data. However, there was a higher rate of thumb
      osteoarthritis in men of any age group. A functional fatigue could provide a
      higher rate of secondary thumb osteoarthritis since the women in this series
      (nuns), who were less affected by overwork, had a rate of primary thumb
      osteoarthritis identical to the rate found in the current literature.

PMID- 11980354
TI  - [Information cards and informed consent. Proposal of 12 information cards for
      plastic and aesthetic surgery].
AB  - Obligation to deliver full information and obtaining enlightened assent are now,
      for the whole French practitioner, a necessary preliminary to each operation.
      Henceforth, in case of suit, the practitioner must prove the reality and the
      quality of preoperative information. The National Medical French Council (CNOM)
      called scientific societies attention to propose to their members some index
      standard cards, corresponding to main medical and surgical records. The National
      Agency for Accreditation and Evaluation in Health (Anaes) defined the main
      characteristics of these documents. The authors propose twelve information cards
      corresponding to the most currently operations of plastic and aesthetic surgery.
      They will being clear and simple, with a large agreement, strictly informative
      and yearly up to date. They have the label and therefore the scientific guaranty
      of French Society of Plastic Reconstructive and Aesthetic Surgery.

PMID- 11980355
TI  - [The fasciocutaneous hypothenar flap: preliminary anatomical and clinical study].
AB  - The authors have studied the vasculatization of the hypothenar area on 11 fresh
      hands. X ray done after injection and dissection under magnification confirm the
      possibility to take a fascio cutaneous flap vascularised by the ulnar digital
      artery of the fifth finger. Three patients who presented a loss of substance of
      the palmar site of the fifth finger received a fascio cutaneous hypothenar flap.
      The donor site was directly closed. This flap was proposed for the loss of
      substance of the palmar site of the fifth finger in competition with the others
      flaps.

PMID- 11980356
TI  - Salivary CA130 with and without unilateral autonomic parotid denervation of rats
      fed different diets.
AB  - BACKGROUND: Tumor markers such as CA130 can be determined in human whole saliva.
      Saliva represents an attractive body fluid for longitudinal studies. MATERIALS
      AND METHODS: CA130 was determined in parotid saliva from 8 rats fed different
      diets, with or without autonomic denervation. RESULTS: CA130 could be determined
      in parotid saliva of rats, irrespective of diet and/or autonomic denervation.
      Whether the numerical decrease in CA130 observed after autonomic denervation is
      statistically significant requires further work. CONCLUSIONS: Since salivary
      CA130 has been shown to decrease following treatment with anti-cancer drugs in
      humans, the ability to determine this tumor marker in rat saliva opens new
      opportunities for optimizing cancer chronotherapy in the experimental laboratory.

PMID- 11980357
TI  - The entelechial genes: a new hierarchy of biological variability.
AB  - Earlier results on the existence of genes affecting variability are revisited in
      the context of effects of phase-shifts on lifespan.

PMID- 11980358
TI  - On the role of the interactions of ions with external magnetic fields in
      physiologic processes and their importance in chronobiology.
AB  - Homage to the scientific work of Franz Halberg is inevitably connected with the
      development and importance of chronobiology and its applications in
      chronomedicine. We show that nonlinear reaction-diffusion systems with
      feedsideward coupling give rise to oscillations between different limit cycles
      favoring either inhibition or stimulation of the growth or decay of a component.
      The inclusion of the diffusion part of each concentration distribution offers the
      possibility of also taking into account the interaction of charged constituents
      with external magnetic fields. Concentration oscillations between different limit
      cycles of the constituents can thus be stabilized. It is assumed that the z
      component of the external magnetic field is related to the rather weak solar
      magnetic field (ca. 10(-9) Tesla). Periods of about one week result for some
      positive (Mg2+, Ca2+, K+) and negative (e.g. Cl-) ions and some organic acids
      containing phosphates. The resonance time of a free proton H+ determining the
      oscillations of the pH-value is about 1 day and that of OH1 is about 3.5 days
      (half a week). The influence of the geomagnetic field (x- or y-component) in the
      same range is of a few to ca. 20-30 minutes in the case of charged proteins. An
      essential condition for this separation is that in general the geomagnetic field
      does not coincide with the z-component of the solar magnetic field. As an
      example, the role of the timedependence of the growth and ATP-concentration of
      the irradiation of the tumor spheroid C3H-MA (mammary adenocarcinoma of mice) is
      presented.

PMID- 11980359
TI  - Generation of classification criteria for chronic fatigue syndrome using an
      artificial neural network and traditional criteria set.
AB  - OBJECTIVE: The definition of chronic fatigue syndrome (CFS) is still disputed and
      no validated classification criteria have been published. Artificial neural
      networks (ANN) are computer-based models that can help to evaluate complex
      correlations. We examined the utility of ANN and other conventional methods in
      generating classification criteria for CFS compared to other diseases with
      prominent fatigue, systemic lupus erythematosus (SLE) and fibromyalgia syndrome
      (FMA). PATIENTS AND METHODS: Ninety-nine case patients with CFS, 41 patients with
      SLE and 58 with FMA were recruited from a generalist outpatient population.
      Clinical symptoms were documented with help of a predefined questionnaire. The
      patients were randomly divided into two groups. One group (n = 158) served to
      derive classification criteria sets by two-fold cross-validation, using a)
      unweighted application of criteria, b) regression coefficients, c) regression
      tree analysis, and d) artificial neural networks in parallel. These criteria were
      validated with the second group (n = 40). RESULTS: Classification criteria
      developed by ANN were found to have a sensitivity of 95% and a specificity of
      85%. ANN achieved a higher accuracy than any of the other methods. CONCLUSION: We
      present validated criteria for the classification of CFS versus SLE and FMA,
      comparing different classification approaches. The most accurate criteria were
      derived with the help of ANN. We therefore recommend the use of ANN for the
      classification of syndromes with complex interrelated symptoms like CFS.

PMID- 11980360
TI  - Molecular therapy via transcriptional regulation with double-stranded
      oligodeoxynucleotides as decoys.
AB  - The number of reports on in vivo gene therapies with decoy ODNs complexed with
      HVJ liposomes has recently increased. Diligent efforts to improve HVJ vectors as
      gene carriers and to expand the therapeutic applications of NFkB and E2F decoy
      ODNs will be important for the improved treatment of many genetic diseases.

PMID- 11980361
TI  - H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with
      various mycelial extracts.
AB  - IL-12 is considered to be one of the most important cytokines in anti-cancer
      therapy. We have demonstrated that substances derived from Basidiomycetes, such
      as active hexose-correlated compound (AHCC) and PSK induce the production of IL
      12. In this study, the MHC dependency of IL-12 production induced by various
      mycelial extracts, PSK, AHCC and IL-X, was examined. During tumor-bearing, higher
      serum IL-12 levels were observed in H-2a and H-2b mice as compared to H-2d mice.
      Concerning the effect of genetic background of mice on response to mycelial
      extracts, AHCC administration enhanced the serum IL-12 level in H-2b mice but not
      in H-2d mice, while PSK administration increased the serum IL-12 level in H-2d
      mice but not in H-2b mice. IL-X, components derived from the same Basidiomycetes,
      also enhanced the serum IL-12 level in H-2b mice in the early stage of tumor like
      AHCC, and maintained serum IL-12 at a level higher than the normal value
      accompanying tumor growth, whereas AHCC did not restore the lowered serum IL-12
      level accompanying tumor growth. These results showed that AHCC or IL-X is
      effective in a genetically Th1-dominant individual whereas PSK is effective in a
      genetically Th2-dominant individual or Th2-dominant status in advanced cancer
      patients. So we propose that the suitable combinations of various mycelial
      extracts may be effective methods of endogenous IL-12 induction for cancer
      patients of all stages, which is important as a cancer therapy that is relatively
      free from adverse reactions and which emphasizes the QOL in individual patients.

PMID- 11980362
TI  - Growth of human glioblastomas as xenografts in the brains of athymic rats.
AB  - BACKGROUND: We have developed xenografts of human glioblastoma (GBM) and
      established the baseline growth parameters and histopathological features of
      these tumors. MATERIALS-METHODS: Cells from 4 different human GBM cell lines were
      injected into the right caudate-putamen of brain in athymic rats. We measured
      tumor weights and the estimated survival time of each rat. RESULTS-CONCLUSION: U
      251 MG and U-87 MG cells produced solid intracerebral tumors with a 100% tumor
      take rate, while SF-767 and SF-126 cells did not grow in the brains of athymic
      rats. Under the conditions employed, U-87 MG tumors grew faster than U-251 MG
      tumors, but both types of tumors exhibited reproducible growth characteristics
      from animal to animal. There was heterogeneity in the growth characteristics and
      histologies between the 2 tumor types, indicating that these tumor models might
      be useful for simulating some of the heterogeneity that occurs between GBM in
      humans.

PMID- 11980363
TI  - Evaluation of drug-induced hepatotoxicity by plasma retinol binding protein.
AB  - Retinol binding protein (RBP) in the plasma of rats treated with D-galactosamine
      was monitored to establish whether its level can be used to evaluate drug-induced
      hepatotoxicity. Blood was withdrawn by heart puncture at 0 hours and 12 hours
      after the administration of D-galactosamine (400 mg/kg body weight i.p.) to rats.
      Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) in the plasma at
      12 hours after the D-galactosamine administration significantly increased, while
      RBP in the plasma at that time significantly decreased. On the other hand, the
      albumin in the plasma was unaffected at 12 hours after the D-galactosamine
      administration. Thus RBP seems to monitor different aspects of drug-induced
      hepatotoxicity than LDH and ALT and to detect the drug-induced hepatotoxicity
      more sensitively than albumin level under the present conditions.

PMID- 11980364
TI  - Antagonist effect of chloroquine and tumor necrosis factor on hepatic oxidative
      stress and antioxidant defense in normal and Plasmodium yoelii nigeriensis
      infected mice.
AB  - BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal
      malaria infection in Swiss albino mice. Tumor necrosis factor (TNF) has been
      implicated in the pathogenesis of malaria by production of reactive oxygen
      species. Chloroquine is a traditionally used antimalarial and has been postulated
      to inhibit TNF secretion during malaria infection. OBJECTIVE: The study the
      comparative effect of chloroquine and TNF treatment on hepatic oxidative stress
      and antioxidant defense indices in normal and P. y. nigeriensis-infected mice.
      MATERIALS AND METHODS: The mice were divided into six groups, each consisting of
      four to six animals. They were normal mice, normal mice treated with chloroquine,
      normal mice treated with TNF-alpha, P. y. nigeriensis-infected mice, P. y.
      nigeriensis-infected mice treated with chloroquine and P. y. nigeriensis-infected
      mice treated with TNF-alpha. RESULTS: Chloroquine treatment of the normal mice
      caused no significant alterations in hepatic oxidative stress and antioxidant
      defense indices while TNF treatment of normal mice caused a significant decrease
      in hepatic superoxide dismutase. Chloroquine treatment of P. y. nigeriensis
      infected mice caused a decrease in blood parasitemia which was accompanied by
      restoration of altered indices to near normal levels. However, TNF treatment of
      P. y. nigeriensis-infected mice had no effect on blood parasitemia but caused a
      significant increase of hepatic xanthine oxidase and lipid peroxidation and a
      decrease in the activity of hepatic superoxide dismutase. CONCLUSION: Exogenous
      TNF acts synergistically with P. y. nigeriensis infection to generate oxidative
      stress in the host and also causes an impairment of the antioxidant defense
      enzyme SOD, while chloroquine treatment reduces the severity of malaria infection
      by decreasing the blood parasitemia and also perhaps by inhibiting the TNF
      release.

PMID- 11980365
TI  - Autoimmunotherapy of type II diabetes with soluble low-molecular-mass antigens: a
      case report.
AB  - AIMS: To study whether autoimmunization of patients suffering from non-insulin
      dependent Type II diabetes with soluble low-molecular-mass antigens (LMA)
      isolated from their serum will activate the immune system and improve clinical
      status. MATERIALS AND METHODS: From March 1998 to July 2000, the patient was
      treated, under observation, with LMA isolated from that same patient. Doses for
      injections varied between 2 and 5 mg of LMA. Injections were performed at weekly
      or monthly intervals. Biochemical studies were performed before injections and 1
      to 2 weeks after them. The following biochemical parameters were determined in
      the blood: levels of glucose, insulin-competitive auto-antibodies (ICAA), a
      glutamine acid decarboxylase (GAD), total concentration of LMA and of the 66 kDa
      and 51 kDa proteins as main representatives of the LMA isolated. RESULTS: The
      patient suffered from high blood glucose levels (BGL), ICAA, GAD, hemoglobin Alc
      and, especially, of LMA and their proteins. Shortarm immunotherapy did not
      improve the parameters studied. However, a regular monthly injection of LMA at a
      dose of 3.5 to 4 mg significantly decreased BGL and reduced the concentrations of
      LMA and their proteins. The whole clinical status of the patient improved and
      became more stable. CONCLUSION: We suggest that vaccination of a diabetic patient
      with LMA activates the host immune system, thereby preventing progress of the
      disease.

PMID- 11980366
TI  - Is implant pacemaker a physicochemical cause triggering Kikuchi-Fujimoto disease?
AB  - A 64 year-old Caucasian female of Greek origin was admitted to hospital with
      painful cervical and axillary lymphodenitis accompanied by fever and night sweats
      for 10 days. The patient had undergone a pacemaker implantation six weeks before
      disease onset because of heart conduction abnormalities. A diagnosis of Kikuchi
      Fujimoto disease was established after lymph node biopsy. The etiology of the
      disease is unknown but viral, bacterial, protozoal; and neoplastic as well as
      physicochemical agents may stimulate a particular immune response. Hereby, we
      hypothesize that the implant pacemaker can act as a physicochemical agent
      triggering Kikuchi-Fujimoto disease. We present this case and we discuss various
      disease aspects. A brief review of the literature is also given.

PMID- 11980367
TI  - [Patients with a chronic recurring psychosis in general practice: the need for
      close follow-up].
AB  - Three patients, a man aged 45, and two women aged 48 and 51 years, were suffering
      from chronic recurring psychoses for which they were taking medication. Their
      general practitioner was alerted to signals of psychotic relapse by the first
      patient himself and for the other two patients by the next of kin. The first two
      patients decided to discontinue their medication, one because he wanted to live
      'a normal life' and the other because she thought the medication made her gain
      weight. The third patient had a psychic decompensation because her son had
      decided to live on his own and because she had also moved. The first two patients
      were successfully treated by restoring their medication, although the second
      patient also had to be referred to a psychiatrist. The third patient had lost
      confidence in the general practitioner, and was eventually admitted to a
      psychiatric clinic for treatment. Nowadays, increasing numbers of chronic
      psychiatric patients are living outside of hospitals. The adequate response of
      general practitioners to psychotic relapse in such patients warrants regular
      contact to evaluate the patient's network and to detect a relapse in an early
      phase. A proactive attitude and being adequately informed by locum general
      practitioners are also important. The extent to which the patient cooperates will
      depend upon the quality of the patient/general practitioner relationship.

PMID- 11980368
TI  - [Care requirements for chronic psychiatric patients in general practice: shared
      responsibility with mental health professionals].
AB  - Every year in the Netherlands, at least 41,000 patients in mental health care
      suffer from long-lasting (> 2 years) psychiatric problems such as psychoses,
      affective disorders, anxiety disorders or personality disorders. A representative
      survey reveals that during certain periods of time about 20% of them only receive
      care from their general practitioner. The general practitioner has to deal with
      the many and complex needs of care in the areas of, for example, psychological
      complaints, psychotic symptoms, social contacts and information about treatment.
      According to the patient, one in four of these needs are unmet, resulting in a
      reduced quality of life. This situation calls for a pro-active attitude on the
      part of the general practitioner who should nevertheless leave the key role in
      managing the care of these patients to the mental health professionals.

PMID- 11980369
TI  - [Shortage in admission capacity for acute cases].
AB  - According to Poolman et al. (this issue), 6% of patients visiting the casualty
      department of a large Amsterdam hospital and requiring hospital admission had to
      be transported elsewhere at the expense of a considerable administrative effort
      on the part of the emergency-care physicians. Contributing factors are the way
      the hospital handles capacity problems, discharge procedures and personnel
      shortages, and, at the level of the city, the system used to allocate budget for
      acute care according to the relative needs of the hospitals. However, the major
      factor is the overall capacity problem in Dutch health care resulting from tight
      budget control. Despite intense discussions, major changes in this system have
      yet to be implemented. In the near future lack of qualified medical and nursing
      personnel will be the main factor that will need to be addressed urgently.

PMID- 11980370
TI  - [Hypertrophic cardiomyopathy: a genetically-carried heart disease].
AB  - Hypertrophic cardiomyopathy (HCM) is a cardiac muscle disease with characteristic
      (mostly asymmetrically distributed) hypertrophy of a non-dilated left ventricle
      in the absence of another cardiac or systemic disease that can cause left
      ventricle hypertrophy. The prevalence of HCM in the general population is
      estimated to be 1 in 500 persons. It is an inheritable disease of the heart with
      a heterogeneous expression and a great diversity of morphological, functional and
      clinical features. The genes involved code for components of a large protein
      complex ('the sarcomere'), which ensures the contraction of the cardiac muscle.
      Electrocardiography, echocardiography and cardiac MRI play a role in the
      diagnosis. Medicinal treatment can improve the diastolic filling and the
      ventricle function. In addition to this there are surgical and non-surgical
      possibilities for myocardial reduction. For patients with life-threatening
      arrhythmias and for the primary prevention of sudden death for high-risk
      patients, an internally implantable cardioverter-defibrillator is indicated. The
      early detection of patients with a predisposition for HCM is only possible by
      means of genotyping.

PMID- 11980371
TI  - [Clinical thinking and decision making in practice. Unexplained rectal blood loss
      in a patient with multiple endocrine neoplasia type 1 syndrome].
AB  - A 55-year-old woman, known with multiple endocrine neoplasia (MEN) type 1, had
      rectal bleeding and later haematemesis but colonoscopy and gastroduodenoscopy
      revealed no abnormalities. Due to the normal results for serum gastrin
      concentration, gastroduodenoscopy and CT scanning of the pancreas, Zollinger
      Ellison syndrome was considered to be less likely. Yet the diagnosis could be
      established on the basis of persistent symptoms and a positive somatostatin
      receptor scintigraphy. The patient was treated with high doses of a proton pump
      inhibitor and temporary tube feeding due to weight loss. Follow-up will take
      place at the endocrinology outpatients' department. Zollinger-Ellison syndrome is
      a relatively common feature of patients with MEN-1. The diagnosis and
      localisation of the gastrinoma can be difficult: serum gastrin concentrations can
      be normal and the sensitivity of CT scanning is low. The primary aim of treating
      gastrinoma is to control gastric acid hypersecretion by means of high doses of a
      proton pump inhibitor. The question as to whether surgery is indicated remains
      controversial.

PMID- 11980372
TI  - [Diagnostic image (84). A woman with persisting perianal fissures].
AB  - A 63-year-old woman had perianal fissures, which were caused by an amelanotic
      melanoma of the anus.

PMID- 11980373
TI  - [Insufficient health care capacity for patients requiring immediate admission; a
      prospective study in a general hospital in Amsterdam, March-November 2001].
AB  - OBJECTIVE: To gain insight into the shortage in health care capacity for patients
      who require immediate admission to hospital. DESIGN: Prospective, descriptive.
      METHOD: During the period 1 March-30 November 2001, data were collected on all
      patients presenting at the casualty department at the Sint Lucas Andreas Hospital
      in Amsterdam, the Netherlands, who had a surgical, internal medicine or
      neurological condition which required immediate admission and who could not be
      admitted due to a shortage in health care capacity. The following data were
      registered: date of transfer, age, gender, diagnosis, referring specialty, time
      of telephone call, accepting hospital and time of acceptance. During the same
      period, the surgery department also noted details of patients requiring immediate
      admission or transfer whom they turned away after presentation via the telephone
      by either the general practitioner or a different hospital. RESULTS: 131 patients
      could not be admitted, 68 men and 63 women with a mean age of 69 years. The
      distribution across the specialties was as follows: surgery: 63 patients (48%;
      mean age: 68 years); internal medicine: 48 patients (37%; 65 years); neurology:
      20 patients (15%; 74 years). The most common reasons for admission were proximal
      femur fractures (24; 18%) and gastrointestinal disorders (27; 21%). Mean duration
      from making the telephone call until acceptance elsewhere was 70 min (range: 1
      330) for surgery, 42 min (5-180) for internal medicine and 116 min (10-870) for
      neurology. The transfer of patients with proximal femur fractures (97 min) and
      cerebrovascular accident (129 min) took the longest. During the same period, 170
      patients were refused by the department of surgery for first-time admission or
      transfer.

PMID- 11980374
TI  - [Melioidosis].
AB  - A 34-year-old woman presented two weeks after a visit to Burma with fever peaking
      up to 39 degrees C, chills, non-productive cough, headache, muscle pain,
      shortness of breath and a painful swelling on the left lower leg. She was treated
      immediately with intravenous amoxycillin-clavulanic acid. The Gram negative
      causative agent of melioidosis, Burkholderia (previously Pseudomonas)
      pseudomallei, was cultured from samples taken beforehand. The patient then
      received ceftazidime. She recovered. In view of the risk of relapse she was
      treated with amoxycillin-clavulanic acid for a further six months. Melioidosis is
      endemic in Southeast Asia and Northern Australia. It is rarely seen outside these
      areas. The clinical spectrum of the disease is wide and varies from fulminating
      sepsis to a subclinical disease and may affect any organ system, usually the
      lungs. The mortality of the septicaemic form after adequate treatment is 40%.
      Surviving patients have a high relapse rate (4-20%). Melioidosis can become
      chronic with formation of abscesses or can remain subclinical for many years,
      probably because the microorganism can survive within phagocytic cells with a
      risk of reactivation at moments of immunosuppression. The optimal treatment
      consists of ceftazidime intravenously for at least two weeks followed by an
      eradication phase consisting of oral antibiotics for at least 3 months.

PMID- 11980375
TI  - [High sensitivity to sulphonylurea treatment in 2 patients with maturity-onset
      diabetes of the young type 3].
AB  - In 2 patients, a 26-year-old woman and a 47-year-old man, diabetes mellitus was
      diagnosed during their teens, although they had (almost) no symptoms at the time.
      Since then, the disease was well controlled in both patients with the use of
      tolbutamide at a low dose. Diabetes occurred in at least 3 generations of both
      patients' families, inherited as an autosomal dominant trait. Genetic screening
      in both individuals revealed two separate mutations in the HNF-1 alpha gene,
      confirming maturity-onset diabetes of the young type 3 (MODY-3). MODY-3 patients
      are unusually sensitive to the hypoglycaemic effects of sulphonylureas. These
      agents remain effective in these patients for years, even at low doses.

PMID- 11980376
TI  - [Female health care workers in the northern Netherlands].
AB  - Women have been members of the surgical guilds since as early as the 14th
      century. Decrees dating from the 16th-18th centuries demonstrate that a number of
      women made a living through surgical practice at that time. From the Middle Ages
      through to the 18th century, women played their role in medical practice, and
      were also involved in surgery. Apart from the common problems of the profession,
      these female practitioners also encountered difficulties related to their gender.

PMID- 11980377
TI  - [Footdrop during pregnancy or labor due to obstetric lumbosacral plexopathy]].

PMID- 11980378
TI  - [Castration of male lambs and calves: explanations and comments of art. 65
      TSchV].
AB  - Since September 1, 2001, castration of male calves and small ruminants in
      Switzerland is not allowed without anesthesia. The use of rubber rings for that
      purpose is forbidden. This change of the legislation has been claimed by the
      Swiss consumers and is aimed to increase the animal welfare. The current paper
      provides a review of the different techniques of anesthesia and castration that
      may be advocated in male ruminants. Sedation with xylazine and injection of
      lidocaine in the area of the base of the scrotum, followed by closed castration
      with the Burdizzo represents a safe technique for painfree castration of calves
      and lambs.

PMID- 11980379
TI  - [Canine panosteitis: an idiopathic bone disease investigated in the light of a
      new hypothesis concerning pathogenesis. Part 1: Clinical and diagnostic aspects].
AB  - Panosteitis, an idiopathic bone disease of young dogs, was investigated in the
      light of a new, empirically based hypothesis governing its pathogenesis.
      Extensive clinical observations suggest a close relationship between the
      incidence of this disease and the commercialization of various protein-rich, high
      calorie dog foods. The theory of an "osseous compartment syndrome" provides a
      hypothetical pathogenesis, which corroborates this findings. An excessive
      accumulation of protein causes intraosseous edema due to its osmotic effects.
      Because bone is a rigid compartment, this leads to an increase in intramedullary
      pressure and compression of blood vessels. Subsequent osseous ischemia leads to a
      deficient metabolic state (decreased oxygenation, inadequate influx of nutritive
      substances, local acidosis, decreased removal of metabolites, disruption of local
      biochemical processes, etc.), and a vicious circle is created due to the
      resulting local inflammation. The disease is aggravated by increased metabolism
      due to excessive physical activity. Within the context of a pilot study,
      clinical, radiographic, scintigraphic and thermographic examinations and a
      therapeutic trial with benzopyron were carried out. In addition, more modern
      investigative tools, including osteomyelography, magnetic resonance tomography
      and intraosseous pressure measurements were used to provide objective data
      concerning the pathogenesis of panosteitis. In most cases, clinical remission was
      seen within days of monotherapy with the proteolytic substance, benzopyron
      (Cumartrin). This finding appears to corroborate our hypothesis.

PMID- 11980380
TI  - Dermatophilosis of Alpine Chamois (Rupicapra rupicapra) in Italy.
AB  - A proliferative dermatitis similar to the condition generally referred to as
      strawberry footrot was observed in two Alpine chamois (Rupicapra rupicapra) from
      Eastern Alps, Italy. Branching septated filaments and packets of PAS-positive
      coccoid organisms were observed in histological sections of the affected skin.
      The actinomycete, Dermatophilus congolensis, was isolated from crusted lesions in
      one chamois. As wild ruminants are presumed to be a reservoir of infection in the
      Alpine area, the authors discuss the potential role of chamois in the
      epidemiology of dermatophilosis.

PMID- 11980381
TI  - [Pigmented skin nodule during carcass examination in a fattening pig].

PMID- 11980382
TI  - Participation of mast cells in colitis inflammation induced by dextran sulfate
      sodium.
AB  - We investigated the participation of mast cells in colitis inflammation induced
      by dextran sulfate sodium (DSS). The damage score and myeloperoxidase (MPO)
      activity were measured to confirm the occurrence of colitis. Rat mast cell
      protease (RMPCP) II levels in the serum were estimated as an index of mast cell
      degranulation. Tissue RMCP I and RMCP II levels in the rectum were also measured
      as markers of the numbers of connective tissue mast cells (CTMCs) and mucosal
      mast cells (MMCs), respectively. Administration of 4% DSS resulted in time
      related increases in damage score, MPO activity and serum RMCP II levels, which
      were statistically significant at 7 and 11 days after treatment. Tissue RMCP I
      and RMCP II levels in the rectum were also increased significantly at 7 and 11
      days, and 11 days, respectively after free drinking of 4% DSS. These results
      suggested that mast cells proliferated or the amount of protease per mast cell
      increased in the sites of inflammation induced by DSS, and that these mast cells
      may modulate the disorders observed in DSS-induced colitis.

PMID- 11980383
TI  - Behavioral effect of herbal glycoside in the forced swimming test.
AB  - We investigated the behavioral effects of Chinese herbal medicines in the forced
      swimming test. One of these medicines, Kami-shoyo-san, induced an antidepressive
      climbing behavior in mice. An effective substance detected to be an O-linked
      glycoside with the sugar chain structure GalNAc alpha 1-3GalNAc was separated.
      The behavioral effect was dose-dependently decreased by the dopamine 2 antagonist
      sulpiride, but not by the dopamine 1 antagonist SCH-233960. Investigated Chinese
      herbal medicines, including Kami-shoyo-san, have been used for human depression.
      These facts suggest that glycoside is one of the antidepressant-like substances
      of Chinese herbal medicines.

PMID- 11980384
TI  - Nitecapone and selegiline as effective adjuncts to L-DOPA in reserpine-induced
      catatonia in mice.
AB  - Reserpine-induced catatonia is a widely accepted animal model of Parkinson's
      disease. In the present study, reserpine (5 mg/kg i.p.) and alpha-methylpara
      tyrosine (AMPT) (200 mg/kg i.p.) induced catatonia in mice 20 h and 1 h before
      the experiment, respectively, as assessed using the rota-rod and bar tests after
      reserpine treatment. There was a significant decrease in fall-off time in the
      rota-rod test and a significant increase in time spent on the bar in the bar test
      as compared to the untreated control mice. Combination therapy with L-DOPA (100
      mg/kg i.p.) and carbidopa (10 mg/kg i.p.) was less effective in reversing
      catatonia as compared to higher doses of L-DOPA (200 mg/kg i.p.) and carbidopa
      (20 mg/kg i.p.), which showed intense hyperactivity in reserpinized mice.
      Pretreatment with nitecapone (30 mg/kg i.p.), a COMT inhibitor, or selegiline (10
      mg/kg i.p.), a MAO-B inhibitor potentiated the motor stimulant actions of
      subthreshold doses of the L-DOPA (100 mg/kg i.p.) and carbidopa (10 mg/kg i.p.)
      combination. Amantadine (40 mg/kg i.p.), but not bromocriptine, potentiated the
      effects of L-DOPA treatment. The NMDA antagonistic action of amantadine may have
      beneficial effects. It is concluded that COMT and MAO-B enzymes play an important
      role in the metabolism of dopamine and administration of a COMT or MAO-B
      inhibitor may prove to be a better adjunct to L-DOPA therapy than a dopamine
      receptor agonist in Parkinson's disease.

PMID- 11980385
TI  - Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine
      in healthy volunteers.
AB  - The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single
      dose of carbamazepine was studied. In a two-way cross-over design with a 1 week
      washout period, 10 healthy volunteers were randomized to received 200 mg
      carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were
      collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug
      administration. Plasma carbamazepine levels were higher with Coca-Cola as
      compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly
      enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The
      results of the study indicate that concomitant administration of Coca-Cola
      enhances the rate and extent of absorption of carbamazepine.

PMID- 11980386
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses, which has been retrieved from the Clinical
      Studies knowledge area of Prous Science Integrity, the world's first drug
      discovery and development portal, providing information on study design,
      treatments, conclusions and references. This issue focuses on the following
      selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab;
      aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride;
      amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone
      dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium;
      cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium;
      darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium;
      esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar;
      fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide;
      glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib
      mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium;
      l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate;
      methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil;
      omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide;
      Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride;
      Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride;
      ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin;
      repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin
      calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium;
      tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost;
      Warfarin sodium; Ximelagatran.

PMID- 11980387
TI  - Enantioselective binding of albendazole sulphoxide to cytosolic proteins from
      helminth parasites.
AB  - The pharmacological effect of the active albendazole metabolite, albendazole
      sulphoxide (ABZSO), depends on its sustained presence at the site of parasite
      location and its binding to helmith beta-tubulin. ABZSO is found in the plasma
      and tissues of albendazole-treated animals in two enantiomeric forms: (+)ABZSO
      and (-)ABZSO. Knowledge of enantioselectivity in drug action is necessary, since
      any difference in target proteins affinity between enantiomers may have
      implications on the pharmacological effect of this anthelmintic molecule. The
      binding of ABZSO to mammalian and helminth parasites cytosolic proteins, as well
      as the differential binding of both enantiomers, were studied. Cytosolic proteins
      from Moniezia expansa (cestode), Ascaris suum (nematode), Fasciola hepatica
      (trematode), rat liver and brain as well as purified porcine brain tubulin were
      used. Drug analysis was performed by HPLC using both C18 and chiral columns.
      ABZSO protein binding was quantitatively different between parasite species
      (4.17, 2.5 and 1.07 ng/mg for cestode, nematode and trematode, respectively);
      this binding to helminth cytosolic proteins was enantioselective. Enantiomeric
      ratios of (-)ABZSO/(+)ABZSO as a percentage were: 43/57 (Ascaris), 36/64
      (Moniezia) and 91/9 (Fasciola). Conversely, the binding of ABZSO to mammalian
      cytosolic proteins showed no enantioselectivity. The overall binding affinity of
      ABZSO for mammalian cytosolic proteins was lower than that observed in helminth
      proteins. The characterization of the comparative binding pattern of ABZSO
      enantiomers to cytosolic proteins from helminth parasites and mammalian tissues
      may contribute to understanding the pharmacological properties of this chiral
      anthelmintic molecule.

PMID- 11980388
TI  - [First do no harm].

PMID- 11980389
TI  - [Chromomycoses (chromoblastomycoses)].

PMID- 11980390
TI  - [Molecular identification of sibling Anopheles species: example of the Anopheles
      minimus and Anopheles dirus complexes, major malarial vectors in Southeast Asia].
AB  - Effective control of malaria vectors requires precise identification of species.
      This is especially important within complexes of species that cannot be
      distinguished based on morphological features. Two methods based on polymerase
      chain reaction (PCR) analysis have been developed to identify 2 species in the
      Anopheles minimus complex and 5 species of the Minimums group as well as 4
      species of the Anopheles dirus complex. Association of oligonucleotide couples in
      the form of multiplex PCR has allowed development of two simple, reliable PCR
      techniques adapted to each one of these species complexes that comprise the major
      vectors of malaria in Southeast Asia. Specifically designed to meet the needs of
      entomologist working in the field for reliable, cost-effective tests, these
      techniques will facilitate assessment of the geographical distribution of each
      vector. These data will help to better target vector control measures.

PMID- 11980391
TI  - [The plague].

PMID- 11980392
TI  - [Anthrax].

PMID- 11980393
TI  - [Smallpox].

PMID- 11980394
TI  - [Congo: transition phase of public health reform].

PMID- 11980395
TI  - [Scurvy, an illness of mariners from the 15th to 18th century , always present].

PMID- 11980396
TI  - [Epidemiologic surveillance of dengue fever in the French army from 1996 to
      1999].
AB  - Dengue fever is a widespread disease that can occur outside tropical areas.
      Several thousand French military personnel are exposed to this infectious risk
      each year and exposure is expected to rise with the creation of a professional
      army and the increasing number of foreign missions. As a result, dengue fever has
      become a major priority for the Armed Services Health Corps (ASHC). A system of
      epidemiological surveillance based on the active participation of all military
      physicians has been designed by the ASHC to collect and analyze all data relevant
      to cases of dengue fever involving French military personnel stationed overseas
      or at home. The purpose of this study is to present data compiled for the period
      from 1996 to 1999. Analysis of these data demonstrated that the incidence of
      dengue fever peaked in 1997 due to epidemic outbreaks occurring in French
      Polynesia and Martinique. In response to these outbreaks control measures were
      adapted especially in regard to vector control. This study shows that the system
      of surveillance implemented by the ASHC is an effective but still perfectible
      tool.

PMID- 11980397
TI  - [West Nile viral meningo-encephalitis in Tunisia].
AB  - In autumn 1997 an epidemic outbreak of meningoencephalitis was observed in two
      coastal districts of Tunisia. A total of 173 cases were recorded with 8 deaths.
      Detection with IgM capture and indirect IgG ELISAs demonstrated West Nile virus
      infection in 86% of patients from whom specimens were collected. West Nile is
      endemic in Asia and Sub-Saharan Africa. Epidemics in humans and horses have also
      been reported in the Mediterranean region and southern European countries.
      However this is the first report in Tunisia. Special West Nile virus surveillance
      is necessary especially in countries at high-risk for repeated introduction of
      this arbovirus.

PMID- 11980398
TI  - [Management of typhoid perforation of the small bowel: a case series in Western
      French Guiana].
AB  - The purpose of this retrospective study of a five-year period in western French
      Guiana is to report our experience in the management of small bowel perforation
      due to Salmonella typhi and to underline the main diagnostic and therapeutic
      pitfalls. Even if clinical and laboratory findings were compatible, final
      diagnosis was reserved until confirmation by postoperative bacteriological
      findings. In patients without advanced peritonitis, excellent results can be
      achieved by excision of the edges of the lesion followed by direct suture in
      cases involving single perforations and by segmental resection followed by end-to
      end anastomosis in cases involving multiple perforations. However these
      techniques cannot be extended to patients presenting severe peritonitis who must
      be treated by bowel diversion.

PMID- 11980399
TI  - [Antimalarial guidelines and therapy practices of the population of Bouake, Ivory
      Coast].
AB  - This survey of 162 households in the city of Bouake, Cote d'Ivoire was undertaken
      to study the behavior of the population in diagnosing and treating malaria.
      Findings indicate that awareness of symptoms and ability to evaluate the severity
      of malaria is high. In most cases, mild malaria is treated at home. In case of
      presumptive diagnosis of malaria, 87.6% of households undertake self-treatment,
      9.3% seek institutional healthcare, 1.2% go to traditional healers, and 1.9% use
      traditional remedies. The most frequent drug for primary treatment is chloroquine
      (68.3%) which is generally obtained from pharmacies (98.8%). However, proper
      dosages are rarely used. If primary treatment fails, behavior is complex
      depending on the estimated severity of disease. Although many causes of malaria
      are mentioned, most people implicate mosquitoes (75.6%). In 95.1% of households
      surveyed, chloroquine prophylaxis was used for newborns. Most households (89.5%)
      practice mosquito bite protection but use of mosquito nets is low (4.9%). These
      results showing the preference for family-based management suggest that
      informational campaigns are needed to promote effective and consistent home
      treatment. Education is also needed to increase knowledge about mosquito nets and
      insecticides.

PMID- 11980400
TI  - [Corneal complications of traditional local ocular treatment in the Democratic
      Republic of the Congo].
AB  - The purpose of this retrospective study was to determine the relationship between
      the use of local traditional eye medicine and the occurrence of corneal ulcers.
      The study population included 53 patients who consulted from January 1998 to
      October 1999 at two hospitals in Kinshasa, Democratic Republic of the Congo,
      after visiting a traditional healer. Clinical examination of the eye was
      performed in all cases and bacteriological tests in most. Local traditional eye
      medicine is used in both urban and rural areas. Factors associated with the use
      of local traditional eye medicine include level of education and social class. A
      cause-and-effect relationship was found between the use of local traditional eye
      medicines and development or worsening of corneal ulcers. Peripheral corneal
      ulcers were the most common. Corneal perforation was more frequent in association
      with peripheral ulcers. Use of traditional eye medicine often leads to corneal
      ulcers with perforation and destruction of the eye in most cases. For this reason
      these practice must be curtailed. However further study is needed to identify the
      active agents in plants used by traditional healers as well as to determine their
      efficacy and toxicity for the eye.

PMID- 11980401
TI  - [Katex for the diagnosis of human visceral leishmaniasis].
AB  - Katex is a latex agglutination test allowing highly specific detection Leishmania
      antigen in urine of patients with visceral leishmaniasis. A multicentric study of
      this new diagnostic tool which is also effective in patients co-infected by
      leishmaniasis and HIV is currently in progress in Sudan, India, Nepal, Brazil and
      Spain. The authors describe the utility of this technique in comparison with
      other routine diagnostic procedures such as microscopic examination and
      serological tests. Preliminary results suggest that it could be used to confirm
      infection in the field and to monitor treatment efficacy.

PMID- 11980402
TI  - [Congenital talipes equino-varus or clubfoot: value of physical therapy (report
      of 189 cases)].
AB  - The purpose of this study was to assess the efficacy of early physical therapy in
      a series of 189 cases of congenital talipes equino-varus (CTEV) or clubfoot.
      Physical therapy alone led to full functional recovery with no complications in
      67 cases (35%). The outcome of treatment was directly correlated with the
      severity of the deformity, early therapy, and regular attendance at treatment
      sessions. Even when full recovery was not achieved, physical therapy led to a
      significant reduction of rigidity and greatly facilitated surgical treatment.
      These findings indicate that it is always valid to recommend physical therapy
      prior to attempting surgical.

PMID- 11980403
TI  - [Oriental biliary lithiasis. Retrospective study of 690 patients treated
      surgically over 8 years at Hospital 108 in Hanoi (Vietnam)].
AB  - The purpose of this study was to review the unique features distinguishing
      Oriental from Western gallbladder disease based on a series of 690 patient who
      underwent surgical treatment at hospital 108 in Hanoi. Oriental
      cholangiohepatitis often affects in young patients with no gender predilection.
      The disease originates mainly in canaliculi and leads to blockage or obstruction
      of the main bile duct inside and outside the liver. Onset has been related to
      nutritional, infectious, and parasitic factors. Ascariasis may play a determinant
      role. Because of these unique features, surgical treatment is usually focused on
      the main bile duct and depends on the size, number, and effects of gallstones.
      The authors recall that excision of liver tissue may be unavoidable in some cases
      due to the severity and consequences of lithiasis.

PMID- 11980404
TI  - [Cholera update at the dawn of the millenium].
AB  - Cholera is an ancestral disease belonging to the mythology of numerous societies.
      In the last two centuries, seven pandemias have been recorded, in which the
      spatial and temporal modalities of disease transmission are related to the major
      technical revolutions of the period. The now ongoing seventh pandemia is by far
      the longest and most widespread with specific features that raise new challenges
      and hopes. The authors present the situation at the dawn of the third millennium
      based on a review of current epidemiological, clinical, therapeutic, diagnostic
      and vaccinal data. This update shows that the field is progressing and may indeed
      be standing on the verge of significant breakthroughs for management of the
      disease and vibrion endemicity.

PMID- 11980405
TI  - [Acute infectious diarrhea: current treatment and perspectives].
AB  - Acute infectious diarrhea is a worldwide public health problem. In developing
      countries it remains a major cause infant mortality despite therapeutic progress,
      especially with regard to the efficacy of oral rehydration, during the last two
      decades. Mortality in industrialized countries is much lower and generally
      stable. In most cases, acute diarrhea is a self-limiting illness that resolves
      with or without symptomatic treatment in a few days. In view of the high
      frequency and generally benign course of diarrheal diseases, management must
      emphasize a cost-effective approach with selective use of available diagnostic
      methods. The initial approach should be based on the patient's history, physical
      examination, and risk factors to identify infections that require more specific
      measures. The purpose of this report is to review currently available drug
      therapies and to describe treatment guidelines for adolescents and adults with
      uncompromised immune systems. Early rehydration is still the mainstay of
      treatment. Use of "etiological" treatment using antimicrobial or antiparasitic
      agents depends on the severity of disease and risk factors.

PMID- 11980406
TI  - [Evaluation of in vitro drug sensitivity of antimalarials for Plasmodium
      falciparum using a colorimetric assay (DELI-microtest)].
AB  - The DELI-microtest (Double-Site Enzyme Linked LDH Immunodetection) is a
      colorimetric method for determination of Plasmodium falciparum in vitro
      sensitivity to antimalarial drugs. This method is based on the capture of the
      specific lactate deshydrogenase of Plasmodium falciparum (pLDH) using 2
      monoclonal antibodies which recognize 2 different sites of the enzyme. The second
      monoclonal antibody is biotinylated and may catch a peroxidase-labelled
      streptavidine and develop a colorimetric reaction in the presence of peroxidase
      substrate. The level of pLDH released by parasite growth is determined by the
      measure of optical densities. An excellent correlation has been observed between
      the IC50's obtained using the DELI-microtest and the classical isotopic
      microtest, and the high sensitivity of the DELI-microtest can be used to measure
      the IC50's for isolates with parasitemia as low as 0.005%. It is easier and
      faster to process than isotopic microtest in field conditions. In addition, due
      to high sensitivity of the DELI-microtest, isolates with a low parasitemia may be
      included in the studies.

PMID- 11980407
TI  - [Bilateral ear myiasis due to Fannia canicularis (Linne 1761)].

PMID- 11980408
TI  - [Typhoid fever epidemic in the Ivory Coast in vaccinated French military
      personnel].

PMID- 11980409
TI  - [Exposure to Toxoplasma gondii and risk of congenital toxoplasmosis].

PMID- 11980410
TI  - [I the caregiver, God the healer].

PMID- 11980411
TI  - [[Let us revive the desire fo life" (interview by Helene Delmotte)].

PMID- 11980412
TI  - [The mission of tuberculosis].

PMID- 11980413
TI  - [Propecia: testimony from monozygotic twins].

PMID- 11980414
TI  - [Social services, care for others].

PMID- 11980415
TI  - [One night with the homeless].

PMID- 11980416
TI  - One handed EMT candidate sues ambulance Co. under ADA.

PMID- 11980417
TI  - Failure to recall & chart pt.'s fall: 'falsus in uno' test. Case on point: Green
      v. St. Francis Hospital, Inc., 2002 WL 371808 NE.2d. -DE.

PMID- 11980418
TI  - PA: nurse has two workers' comp. claims: court order prohibits comp. claim
      "stacking".

PMID- 11980419
TI  - PA: psych pt. with "kill" wish released by nurse: nurse is terminated-
      arbitration results.

PMID- 11980420
TI  - Refusal to be party to 'trumped-up' charges--retaliatory termination. Case on
      point: Gerard v. Camden Cnty. Health Srvcs. Ctr., N.J. Supr.App.Div. 3/6/2002-NJ.

PMID- 11980421
TI  - [Osteoporosis: a risk factor for periodontal disease (literature review)].
AB  - Osteoporosis is a major public health problem all over the world. Caucasian women
      have the highest risk. Osteoporosis affects about 10% of the total population but
      the prevalence among postmenopausal women is more than 30%. It had long been
      stated that general osteoporosis played no role in the etiology of destructive
      periodontitis with inflammatory nature. Nevertheless a substantial number of
      publications in recent years indicated just an opposite relationship. It has been
      shown that total body calcium and bone density was closely associated with
      mandibular bone density and several studies have demonstrated close relationship
      between edentulism and systemic osteopenia. Certain data showed clear
      relationship between osteoporosis and periodontal disease, and osteoporosis is
      considered as one of the risk factors for periodontal bone loss. Both
      osteoporosis and periodontal disease are chronic multifactorial diseases with
      many genetic and behavioral risk factors and determinants. Both diseases can be
      successfully controlled by eliminating several risk factors. Estrogen replacement
      therapy can be protective against both postmenopausal osteoporosis and severe
      periodontitis in postmenopausal women. Tobacco smoking and diet are also
      important risk factors for both diseases and genetic factors have also been
      identified as important risk factors in the etiology of both diseases. Recent
      epidemiological and clinical data provides limited but convincing evidence
      suggesting an association between osteoporosis and periodontal disease, and many
      common risk factors could have been detected in the etiology of both diseases.

PMID- 11980422
TI  - [Mathematical classification of root canal curvature of human teeth].
AB  - Endodontic research requires a mathematically based classification method of root
      canal forms. The aim of this study was to give a mathematical description of root
      canal forms using differential geometrical pattern analysis and computer
      graphics. The measurements of 433 extracted human roots were carried out on
      isometric radiographs taken from clinical view. Seven points of root canal axis
      of the same radiographs were approximated using fourth degree polynomial
      functions describing the imaginary axis of canals. The Schneider's angle of each
      root was also measured for grouping the samples according to this parameter. The
      classification of root canal form on the basis of Schneider's angle differs from
      the classification of geometrical pattern analysis. This type of classification
      of root canals is suitable for standardizing test specimens, including natural
      human teeth used for testing root forms: I (straight), J (apically curved), C
      (continuously curved) or S (multicurved).

PMID- 11980423
TI  - [Platysma myocutaneous island flap reconstruction after excision of a tongue
      tongue base tumor].
AB  - The authors' aim was to introduce a simple, safe and reliable method for
      reconstruction of soft tissue defects after excision of carcinomas of the tongue,
      tongue base and posterior part of the floor of the mouth. The musculocutaneous
      flaps are options of larger soft tissue defects in the maxillofacial area. After
      excision of a tongue-tongue base tumour with mandibular splitting method a
      platysma myocutaneous flap was applied for reconstruction. The flap was taken
      from an appropriate place convenient to functional acceptions and was adapted
      anatomically into the defect. The result was that the patient healed primarily
      with undisturbed blood circulation of the flap. The functional rehabilitation
      period was short, the flap tolerated the irradiation. The authors observed that
      the use of the platysma island flap can be an option for reconstruction of
      defects after ablative surgery on the tongue-tongue base. This simple method
      worked reliable even after intra-arterial cytostatic treatment. The acceptable
      functional result depends on the placement of the island flap on the neck flap
      prepared for neck dissection.

PMID- 11980424
TI  - [Follow-up examinations after removal of titanium plates coated with anodic
      titanium oxide ceramic].
AB  - Transformation of the titanium metal surface with titanium oxides produced in
      various ways belongs among the most up-to-date procedures. The authors as
      pioneers in this field (e.g. Nobel Biocare TiUnite surface), have been utilizing
      for more than 15 years dental root implants and fixing elements (for mandibular
      osteosynthesis) coated with titanium oxide ceramics, produced by anodic oxidation
      and thermal treatment. The aim of this work was to assess the extent to which a
      titanium oxide ceramic coating influences the fate of plates applied for
      osteosynthesis within the human body. During a 5-year period (1995-1999), 108 of
      1396 titanium oxide ceramic plates had to be removed for various reasons:
      loosening of the plate [47], osteomyelitis [25], a palpable swelling and
      tenderness [21] at the request of the patient for psychological reasons (13) or
      breaking of the plate [2]. When these 108 plates were removed, it was not
      possible to detect metallosis in even a single case; nor was there any tissue
      damage that could be attributed to the surface of the plates, whereas the
      literature data indicate that such damage is relatively frequent in the
      environment of traditional titanium fixing elements. The present investigation
      confirms the favourable properties of the titanium oxide ceramic surface.

PMID- 11980425
TI  - [Mixed and palatal salivary secretion in denture-wearing healthy people and in
      patients with Sjogren syndrome].
AB  - Denture retention is related to forces necessary to completely remove the denture
      from its basal seat. The liquid-joint model for explaining denture retention is
      accepted by most of the authors. According to this model retentive force is a
      function of saliva surface tension, liquid film thickness, surface of contact and
      the liquid-denture contact angle. Based upon the literature, mucosa covered with
      the least amount of saliva exists at the area of the palate and the upper lip,
      consequently at the area of the upper denture retention. Dryness is dependent on
      the volume of saliva present on the oral mucous membranes and the rate of its
      evaporation of them. However, the hard palate contains few minor glands and it is
      an area of high evaporation. Based on the above mentioned facts, patients with
      xerostomia might have problems with the stability of the complete dentures. To
      verify it, authors investigated 24 healthy people and 11 patients with Sjogren's
      syndrome (SS). Further aim of the authors was to determine how the new dentures
      influence the whole resting and the palatal saliva flow rate. According to the
      results whole resting saliva flow rate is decreased in SS because of the focal
      inflammation of the salivary glands, but surprisingly the palatal secretion rate
      does not change in SS related to the initial values of the healthy people.
      Although every patient had xerostomia (WRS < or = 0.1 ml/min), none of them
      complained about denture instability. Based upon this study, authors agree with
      the statement of the literature, that palatal mucous saliva can help to stabilize
      the maxillary denture. Results suggest that whole resting and palatal saliva flow
      rates are not influenced by the placement of new dentures in healthy complete
      denture wearers.

PMID- 11980426
TI  - [Periodontal disease and general health--literature review].
AB  - Periodontal disease is a significant cause of alveolar bone resorption resulting
      ultimately in the loss of teeth. Inflammation of the periodontal tissues is
      initiated by bacteria of the oral micro-flora. Invading micro-organisms stimulate
      both protective and destructive inflammatory-immune responses involving cytokine
      release syndrome, chemokines, arachidonic acid metabolites, reactive oxygen and
      nitrogen intermediates, and matrix melloproteinases. The local infection may
      affect general health in two ways. First, transient bacteremia from the oral
      focus may result in metastatic infection in remote organs of susceptible hosts,
      such as bacterial endocarditis in patients with congenital or acquired heart
      diseases. Second, lipopolysaccharide and inflammatory mediators are not only
      involved in local tissue destruction but have the potential to modulate the
      course of cardiovascular, chronic obstructive lung and autoimmune diseases,
      diabetes mellitus and preterm birth. Epidemiologic observations, awaiting further
      verification by controlled prospective trials, underline the impact of oral
      health on general well-doing.

PMID- 11980427
TI  - [Effect of interocclusal records on the condylar path of the articulator].
AB  - Although there are studies on materials used for interocclusal records, there are
      no scientific data how the condylar path is influenced by the positional
      interocclusal records. The purpose of this in vitro study was to determine the
      effects of different interocclusal mediums on condylar inclination of the
      articulator. The materials selected for this experiment were: two addition type
      silicone pastes, two silicone putty materials and two waxes. The samples of
      protrusive records were performed on a Quick-Master semiadjustable articulator
      (FAG Dentaire). The same pre-established eminentia angles were used during the
      experiment for each type of materials. To improve the control of the condylar
      angles a protractor was mounted to the upper member of the articulator at right
      angels to each condylar fossa housing. A stylus moving simultaneously with the
      condylar fossa marked the eminentia angle on the protractor. 108 interocclusal
      records were performed and in 24 hours they were returned to the articulator.
      Then the articulator was adjusted and the settings of the eminentia angle were
      recorded. Numerical deviations between the pre-established and the adjusted
      settings in degrees were subjected to statistical analysis. The results indicated
      that these deviations for addition type silicones were significantly smaller than
      that of the other materials. The two waxes proved to be the least accurate
      materials. It is concluded that the condylar inclination is influenced by the
      properties of the registration materials, which may increase the shortcomings of
      the protrusive bite records.

PMID- 11980428
TI  - [Computer-assisted coronary surgery].
AB  - Routine totally endoscopic, beating heart, coronary surgery should be made
      possible by the use of computer enhanced surgical techniques. It includes a
      totally endoscopic mammary artery harvesting, a correct exposure and an adequate
      stabilization of the coronary artery at the anastomotic site, a perfect
      anastomosis of the mammary artery on the left anterior descending coronary artery
      using a microsurgical suture technique. This complex surgical protocol will be
      reached by a step by step approach. The first 20 patients who accepted to be
      operated with tele-manipulated instruments make the substance of this first
      report. In 19 cases, the dissection of the internal mammary artery could be
      performed with an optimal result: the lack of bleeding during the dissection
      emphasizes the excellent visualization of the operative field and the precision
      of the dissection. The satisfactory blood flow in the mammary artery at the time
      of the coronary anastomosis suggests the lack of spasm and confirms the
      atraumatic dissection. The distal anastomosis of the coronary bypass has been
      performed through a mid line sternotomy to avoid an excessive prolongation of the
      operative time. The anatomic conditions and the quality of the vessel wall
      allowed to perform the coronary anastomosis with the tele-manipulated instruments
      in nine cases only: in six patients, the mammary artery has been implanted on the
      descending artery, in three, a venous autograft on the diagonal branch. Our
      initial clinical experience with this new technique suggests that a very precise
      and fine surgery can be performed with an acceptable prolongation of the
      operative time. More experience and further developments in the instrumentation
      are nevertheless required to allow completion of the entire procedure totally
      closed chest, on a beating heart.

PMID- 11980429
TI  - Nothing to be sneezed at.

PMID- 11980430
TI  - Young love.

PMID- 11980431
TI  - Men in nursing. We happy few.

PMID- 11980432
TI  - Effects of a cognitive acceleration programme on Year 1 pupils.
AB  - BACKGROUND: Cognitive Acceleration has shown evidence of long-term far transfer
      with young adolescents. This paper reports a new application of the principle to
      5- and 6-year-olds in a disadvantaged inner city area. AIMS: To investigate the
      effect of a cognitive intervention programme on the cognitive development of
      children in Year I of primary schools. SAMPLE: Approximately 300 children in 14
      Year 1 classes in 10 schools for the experimental group and 170 children in 8
      classes in 5 matched schools as controls. METHOD: Quasi-experimental pre-test
      post-test with experimental and matched control groups. One of the pre- and post
      tests was intended to probe for transfer. Children in experimental classes
      experienced a set of 29 activities designed to promote cognitive conflict and
      encourage social construction and metacognition over one school year. RESULTS:
      The experimental group overall made significantly greater gains in cognitive
      development over the period of the experiment than the controls, in both
      direct(effect size 0.47) and transfer (effect size 0.43) tests, although when
      genders were considered separately, experimental boys' greater gains than
      controls did not reach significance. There was no interaction with various social
      and linguistic variables. CONCLUSION: In the context of this study, a cognitive
      intervention programme can have a significant immediate effect on the rate of
      children's cognitive development. Further work will investigate the longevity of
      this effect.

PMID- 11980433
TI  - Creating a better future.

PMID- 11980434
TI  - Creating a Potemkin Village: HIPAA 'quick fix' is just an illusion.

PMID- 11980435
TI  - [Viral hepatitis C and diabetes].

PMID- 11980436
TI  - [Risk of H. pylori-related cancer of the stomach was underestimated].

PMID- 11980437
TI  - Clemens von Pirquet and the concept of allergie.

PMID- 11980438
TI  - Functional MDR1 polymorphisms (G2677T and C3435T) and TCF4 mutations in
      colorectal tumors with high microsatellite instability.
AB  - The multidrug resistance 1 (MDRI) gene and transcription factor 4(TCF4) gene are
      suggested to be involved in the WNT signalling pathway, the most important
      pathway altered in colorectal cancer. Mutations in both genes have been
      identified and associated with colorectal tumors exhibiting high microsatellite
      instability (MSI-H). In this study, we report on the distribution of functional
      polymorphisms in the MDR] gene and somatic frameshift mutations in the TCF4 gene
      coding mononucleotide repetition in 62 MSI-H colorectal tumors. Somatic
      frameshift mutations in(of) the TCF4 gene were identified in 24/62 (39%) of the
      studied MSI-H tumors. The estimated allele frequencies of functional
      polymorphisms in(of) exon 21 (2677 G>T, Ala893Ser) and exon 26(3435 C>T, Ilel
      142I1e) of the MDR] gene were 0.42 and 0.46 in the controls and 0.54 (p=0.035)
      and 0.60 (p=0.017) in the MSI-H tumors. However, the allele frequency of both
      functional MDR] polymorphisms did not significantly differ between MSI-H tumors
      with TCF4 mutations and those without. These results support the involvement of
      the MDRI gene in the tumorgenesis of MSI-H tumors and also suggest that
      functional polymorphisms in the MDRI gene and mutations in the TCF4 gene are
      likely to occur independently in MSI-H tumors.

PMID- 11980440
TI  - [Editorial].

PMID- 11980439
TI  - Patellar or hamstring tendons in anterior cruciate ligament reconstruction: a
      meta-analysis.

PMID- 11980441
TI  - Figuring out info tech's ROI.

PMID- 11980442
TI  - Keep that chief.

PMID- 11980444
TI  - Workforce commission. In our hands.

PMID- 11980443
TI  - Coverage and access. A better outcome.

PMID- 11980445
TI  - Hydrocarbon degraders from tropical marine environments.
AB  - Analysis of 20 samples of marine mud and water around Mumbai resulted in the
      isolation of 17 bacteria and yeasts all of which were able to degrade more than
      10% of the supplied crude oil. The yeasts strains were important degraders of the
      aliphatic fraction of crude. All the isolated yeasts belonged to the genus
      Candida. Using biochemical tests these were identified as Candida parapsilosis,
      C. albicans, C. guilliermondii, Yarrowia lipolytica, C. tropicalis and C.
      intermedia. Y. lipolytica was the best degrader utilizing 78% of the aliphatic
      fraction of Bombay High crude oil. None of these isolates degraded the aromatic
      or ashphaltene fractions. All the isolates required aeration, nitrogen and
      phosphate supplementation for optimal degradation. Four out of the six yeasts are
      human pathogens.

PMID- 11980446
TI  - Persistent organochlorine residues in sediments from the Black Sea.
AB  - The extent of contamination of the Black Sea by selected organochlorine compounds
      has been assessed through the analysis of surficial sediments taken from
      throughout the region. Concentrations of HCHs at sites influenced by the Danube
      delta are among the highest recorded on a global basis (up to 40 ng g(-1) dry
      wt). The ratio between the alpha- and gamma-isomers was relatively low indicating
      contamination through the use of lindane. Concentrations of DDTs (0.06-72 ng g(
      1) dry wt) and PCBs (0.06-72 ng g(-1) dry wt) were not especially high in
      comparison to levels reported from throughout the world. The DDE/DDT ratio was,
      however, low indicating fresh inputs and hence current usage of DDT within the
      Black Sea region.

PMID- 11980447
TI  - Metal contaminants for modelling lobster (Homarus americanus) migration patterns
      in the Inner Bay of Fundy, Atlantic Canada.
AB  - A method, which uses metal compositions in lobster digestive glands as natural
      environmental tags, has been developed to trace lobster movements. Lobsters were
      collected from three selected sites, Minas Channel, Minas Basin, and Cobequid
      Bay, Inner Bay of Fundy, New Brunswick, Canada, that were known to be
      contaminated with Cu. Five metal variables (Ag, Cd, Cu, Mn and Zn) were processed
      for principal component analysis (PCA). Metal concentration and burden models
      were investigated and PCA was able to differentiate lobsters from the respective
      catch sites. The method was applied to investigate the May and June lobsters
      collected at the three sites to determine the migration rate during this period
      of the fishing season. The results show a high level of mixing at Minas Basin and
      Cobequid Bay in June, and lobster movement inward toward the inner reaches of the
      bay, with very limited movement outward from the inner bay.

PMID- 11980448
TI  - Contamination by organochlorine compounds in walleye pollock (Theragra
      chalcogramma) from the Bering Sea, Gulf of Alaska and the Japan Sea.

PMID- 11980449
TI  - Be wary of health discount cards.

PMID- 11980450
TI  - Attachment and meaning-making in perinatal bereavement.
AB  - The study examined the psychological impact of perinatal bereavement on 108
      women, from a dual attachment and meaning-making perspective, both descriptively
      and predictively. The study hypothesized that grief acuity is a function of both
      attachment security (operationalized by A. Antonovsky's 1979 Sense of Coherence
      [SOC] scale), and the ongoing search for meaning. Controlling for time post-loss,
      psychological distress and intrusive thoughts; sense of coherence and search for
      meaning significantly predicted current grief acuity. The findings supported the
      conceptualization of grief as an interpretive phenomenon, elicited by the loss of
      a primary attachment figure, thereby shattering core life purposes, and
      implicating the need to reinstate meaning.

PMID- 11980451
TI  - "Fret no more my child ... for I'm all over heaven all day": religious beliefs in
      the bereavement of African American, middle-aged daughters coping with the death
      of an elderly mother.
AB  - This article examines the ways in which religious beliefs of 30 African American,
      middle-aged daughters help them cope with the death of their elderly mothers.
      This qualitative, exploratory study found that daughters use their beliefs to
      move through states of grief that allow them to prepare, relinquish control,
      accept death, and maintain a connection to their mothers beyond death. Important
      themes identified in this study include the belief in an after life and the
      reunification of family members there. Findings suggest that religious beliefs
      provide a means for adult daughters to cope with the tasks of living in the
      present yet maintain a tie with their deceased mothers that serves to enhance
      their religious beliefs and fortitude in daily living.

PMID- 11980452
TI  - College students' perceptions of suicide: the role of empathy on attitudes,
      evaluation, and responsiveness.
AB  - A total of 334 college-age students (18719 years) participated in a study
      investigating the role of empathy in perceptions of and responsiveness toward a
      hypothetical friend exhibiting symptoms associated with suicide risk. High
      empathy participants viewed both affective and behavioral characteristics
      associated with suicide risk as more serious, and they were more likely to
      provide direct assistance and talk with the troubled peer. Gender of participant
      and type of symptom displayed also emerged as important factors in participants'
      evaluations. These findings underscore the importance of considering social
      cognitive factors that may influence perceptions of at-risk behaviors. The
      implications of these findings for the development of primary prevention
      intervention efforts are discussed.

PMID- 11980453
TI  - Social values and decision making: a generation in the lifeboat.
AB  - The author introduced the "Lifeboat"exercise as a death-and-dying teaching
      technique in an article that appeared in the first volume of Death Studies (J.
      A.Thorson, 1978). It is a classroom exercise designed to illustrate the varying
      levels of social value placed on terminally ill patients. Using "Lifeboat" with
      different groups in succeeding years, the author has seen changes in the ways
      that individuals playing different roles are perceived by the audience. These
      reactions may indicate changes in social values.

PMID- 11980454
TI  - Medical devices; ear, nose and throat devices; reclassification of the
      endolymphatic shunt tube with valve. Final rule.
AB  - The Food and Drug Administration (FDA) is reclassifying the endolymphatic shunt
      tube with valve from class III (premarket approval) into class II (special
      controls). The device is intended to be implanted in the inner ear to relieve the
      symptoms of vertigo and hearing loss due to endolymphatic hydrops (increase in
      endolymphatic fluid) of Meniere's disease. FDA is also identifying the guidance
      document entitled "Class II Special Controls Guidance Document: Endolymphatic
      Shunt Tube With Valve; Guidance for Industry and FDA" (the guidance) as the
      special control that the agency believes will reasonably ensure the safety and
      effectiveness of the device. This reclassification is based on new information
      submitted in are classification petition by E. Benson Hood Laboratories, Inc.
      (Hood Laboratories). FDA is taking this action under the Federal Food, Drug, and
      Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976, the
      Safe Medical Devices Act of 1990, and the Food and Drug Administration
      Modernization Act of 1997. Elsewhere in this issue of the Federal Register, FDA
      is publishing a notice announcing the guidance.

PMID- 11980455
TI  - Pneumonia.
AB  - Pneumonia is the leading cause of mortality and a common cause of morbidity in
      children below five years of age. Commonly, pneumonia is caused by bacterial
      agents. The diagnosis of pneumonia is usually made on clinical features. A child
      with tachypnea with no chest in-drawing or difficulty in feeding is labeled as
      pneumonia. Presence of chest in-drawing, difficulty in speech, feeding or
      cyanosis classifies a child as suffering from severe or very severe pneumonia.
      Factors that may help in selection of appropriate antibiotics include: knowledge
      of etiological agents, sensitivity of pathogens to antibiotics, severity of the
      disease, immune status, nutritional status, previous antimicrobial usages,
      history of hospitalization, duration of illness, associated complications and
      cost and safety of antibiotics. For selection of antibiotics pneumonia can be
      classified in two major categories (a) community acquired, without risk factors,
      and (b) pneumonia with risk factors. Both these can be further classified as non
      severe and severe illness. A community acquired pneumonia in a child between 2
      months -60 months without risk factors for resistant or atypical organism may be
      treated with amoxicillin. The alternative to amoxicillin includes oral
      cephalosporins and cotrimoxazole. In pneumonia with presence of risk factors the
      antibiotics are decided on basis of individual patients characteristics. A child
      with non-severe pneumonia should be treated with oral cefuroxime or amoxicillin
      clavulinic acid for a period of 7-14 days.

PMID- 11980456
TI  - Otitis media.
AB  - There is a high rate of use of antimicrobial drugs for otitis media in children.
      This article reviews the diagnostic considerations for acute otitis media. An
      extensive review of literature on this subject has been carried out in order to
      address the issues of indications, choice, appropriate doses of antimicrobial
      agents and the duration for which they should be used. It is important to
      distinguish acute otitis media from otitis media with effusion because
      antibiotics are seldom indicated for the latter condition. Oral amoxicillin
      remains first-line therapy for uncomplicated acute otitis media, a short course
      of antimicrobial therapy (five to seven days) may be appropriate in children two
      years of age or older with uncomplicated presentations. For clinical treatment
      failures after 3 days of amoxicillin, recommended antimicrobial agents include
      oral amoxicillin/clavulanate, cefuroxime axetil, cefprozil, cefpodoxime proxetil,
      and intramuscular (i.m.) ceftriaxone. Tympanocentesis for identification of
      pathogens and susceptibility to antimicrobial agents is recommended for selection
      of third-line agents.

PMID- 11980457
TI  - Rational antibiotics therapy in bacterial meningitis.
AB  - Acute bacterial meningitis is one of the most important causes of morbidity and
      mortality in developing countries. Though a wide range of antibiotics is
      available for therapy, judicious and rational use of antimicrobial agents needs
      to be ascertained. The choice of antimicrobial agents depends mainly on the age
      of the patient and its CSF penetrability. Neonatal meningitis is commonly caused
      by Gram Negative organisms such E. coli, Klebsiella and Pseudomans;Group B
      streptococciand Listeria, though other organisms like Staphylococcus sp. also
      contribute. The neonatal meningitis is best treated with a combination of
      amplicillin and a third generation cephalosporin given for 14-21 days. Post
      neonatal meningitis usually occurs due to S. pneumoniae, N. meningitidis and H.
      influenzae and is best treated with third generation cephalosporins used with or
      without crystalline penicillin or ampicillin depending on the clinical situation.
      The therapy should be modified, if necessary, on availability of culture
      sensitivity report. The use of dexamethasone in meningitis due to the organisms
      other than H. influenzae still remains controversial.

PMID- 11980458
TI  - Urinary tract infections: evaluation and treatment.
AB  - Urinary tract infections (UTI) are the second most common bacterial infection in
      children after those of the respiratory tract. These infections are important in
      view of their acute morbidity and the long-term risk of renal scarring.
      Occurrence of UTI below two years of age, delay in starting treatment and
      presence of vesicoureteric reflux or obstruction are the chief risk factors
      associated with renal scarring. The classical features of UTI are absent in young
      children, who often present with few signs or symptoms other than fever. Since
      the diagnosis of UTI warrants a thorough evaluation subsequently, empiric
      treatment based on symptoms or urinalysis alone should be avoided. Therapy with
      appropriate antibiotics is started only after obtaining a urine culture. The
      distinction between upper and lower urinary tract infections is difficult and the
      choice of therapy guided by the patient's age and severity of clinical
      manifestations. All children with UTI should be investigated to identify those
      with an underlying urinary tract anomaly.

PMID- 11980459
TI  - Skin and soft tissue infection.
AB  - Abstract. Normal skin is heavily colonized by bacterial flora. The most common
      are the various nonpathogenic gram-positive bacteria such as Staphylococcus
      epidermidis (coagulase-negative). Skin and soft tissue infections are usually
      caused by Staphylococcus aureus (S. aureus) and Streptococcus pyogenes. This
      article discusses common and some not so common bacterial skin infections,
      including impetigo, folliculitis, furncles and carbuncles, cellulitis and
      erysipelas, gangrenous cellulitis, staphylococcal scalded skin syndrome and
      scarlet fever. Impetigo and ecthyma are common bacterial infections of the skin
      commonly caused by S. aureus and / or Group A streptoccus. In mild and localized
      impetigo topical antibiotics whereas in widespread or severe one and in ecthyma
      systemic antibiotics like, cloxacillin, erythromycin, azithromycin or cephalexin
      should be used. Folliculitis, furunculosis and carbuncle are folliculocentric
      infections caused by S. aureus involving the variable depth and extent of the
      follicle(s) and surrounding tissue. These conditions can be treated with topical
      or systemic antibiotics like cloxacillin, cephalexin, erythromycin,
      amoxicillin/clavulanic acid or vancomycin. Staphylococcal scalded skin syndrome
      is a toxin mediated exfoliative dermatosis caused by S. aureus of phase group II.
      Intravenous penicillinase-resistant anti-staphylococcal antibiotics like
      methicillin, cloxacillin, cephalosporin or erythromycin are required. Erysipelas
      and cellulitis are acute infections of dermal and subcutaneous tissues caused
      most frequently by Group A beta-hemolytic streptococci (erysipelas) or S. aureus
      requiring systemic antibiotics like oral or intravenous penicillin, erythromycin,
      cephalexin, cloxacillin, vacomycin, minocycline or ciprofloxacin depending upon
      the severity, suspected causative organism and culture/sensitivity results.
      Gangrenous cellulitis is characterized by infection with necrosis of skin and
      underlying subcutaneous tissue due to various pathogens occurring at different
      site. Ampicillin, gentamicin, and either metronidazole or clindamycin
      intravenously in standard doses are recommended for the treatment.

PMID- 11980460
TI  - The introduction of antibiotics in 1940's revolutionized the practice of
      medicine.

PMID- 11980461
TI  - Intestinal infections.
AB  - Gastrointestinal infections are the significant cause of childhood morbidity and
      mortality worldwide. Gastrointestinal infections reflects the balance between the
      intrinsic virulence factors of the enteropathogens and host mechanisms which
      defend against enteric infections. Host defense factors include gastric acidity,
      intestinal motility, the normal indigenous intestinal microflora, mucous
      secretion, and specific mucosal and systemic immune mechanisms. Majority of GI
      infections are self limited so on one hand antibiotics are not needed and on the
      other hand the irrational use of antibiotics produces resistant strains. Acute
      diarrheal diseases which are one of the important intestinal infections, in
      majority of the cases are viral and have short course. Antibiotics are
      recommended only in specific cases and in immunocompromised individuals.
      Gastrointestinal disease is one of the most common manifestations of HIV
      infection. The gastrointestinal tract contains abundant quantities of lymphoid
      tissue and is likely to function as a reservoir of HIV infection, a site of
      profound immune dysregulation, and a target for opportunistic infections. In this
      situation specific antibiotics are indicated.

PMID- 11980462
TI  - Childhood asthma--a challenge to pediatricians.

PMID- 11980463
TI  - Drug therapy of childhood asthma.
AB  - Drug therapy is used to prevent and control asthma, and also to reduce the
      frequency and severity of its exacerbations, and reverse airflow obstruction.
      Asthma medications are thus categorized into two general classes--bronchodilators
      (relievers) and anti-inflammatory drugs (preventers). Short acting beta2-agonists
      is the therapy of choice for relief of acute symptoms and prevention of exercise
      induced bronchospasm (EIB). Corticosteroids are the most potent and effective
      anti-inflammatory medication currently available. Inhaled form is used in the
      long-term control of asthma. Systemic corticosteroids are used to gain prompt
      control of the disease when initiating long-term therapy. Long acting
      bronchodilator used concomitantly with anti-inflammatory medications for long
      term control of symptoms, especially nocturnal symptoms. Ipratropium bromide may
      provide some additive benefit to inhaled beta2-agonists in severe exacerbations.
      Sustained release theophylline is a mild to moderate bronchodilator used
      principally as adjuvant to inhaled corticosteroids for prevention of nocturnal
      asthma. Leukotriene modifiers may be considered as an alternative therapy to
      inhaled corticosteroids or cromolyn or nedocromil.

PMID- 11980464
TI  - Aerosol delivery systems in childhood asthma.
AB  - Asthma in younger children appears to be increasing in prevalence, whilst at the
      same time it is recognized that inhaled corticosteroids and bronchodilators are
      the mainstay of treatment for this condition. Presently the devices available for
      aerosol treatment of young children are mostly developed for use in older
      children and adults. However, an awareness of the need for delivery systems
      dedicated to use by young children is increasing. The devices available at
      present for aerosol treatment of young children comprises the nebulizer, metered
      dose inhaler with spacer, and dry powder inhaler. The inhaler strategy found most
      useful at present can be summarized as follows: children younger than 2 years can
      use MDI+spacer+mask or nebulization, while children above 2 years can use
      MDI+spacer (without mask). Older children (3-4 years) can be easily taught the
      use of a Rotahaler.

PMID- 11980465
TI  - Management of acute asthma.
AB  - Hospitalization due to acute severe asthma represents a failure in the
      preventive, long-term as well as home care of asthma. Recognition of danger signs
      and prompt treatment can prevent the risk of morbidity and mortality of an acute
      asthma episode. The principle pharmacological management is use of inhaled beta2
      sympathomemetrics and systemic steroids given with monitoring of respiratory
      status with the help of clinical parameters and pulmonary function tests. In
      patients non responsive to routine management, there is a role of inhaled
      cholinergic compounds, intravenous magnesium sulphate, and beta2 sympathomemetic
      infusion. Patients in respiratory failure need intensive care. Carefully managed
      prognosis of an acute attack of asthma is good.

PMID- 11980466
TI  - Natural history of asthma in children.
AB  - Asthma is a syndrome of reversible bronchial obstruction in hyperresponsive
      airways mediated by allergy or other trigger factors. Allergic disease represents
      true asthma while transient wheezing may be caused by factors such as viral
      infection, aspiration, prematurity and neonatal lung damage and is likely to
      outgrow within few years. Personal or family history of atopy, increased serum
      IgE and positive skin tests may suggest allergic asthma, which persists
      throughout life irrespective of presence or absence of symptoms. Onset of age
      beyond 2 years, severity, persistence or recurrence of symptoms beyond 6 years of
      age, airway hyperresponsiveness and abnormal lung function even in absence of
      symptoms, strong family history especially in the mother, exposure to allergens,
      parental smoking and delay in starting appropriate therapy are some of high risk
      factors in persistence of asthma in adult life. As outcome of asthma depend upon
      multiple variable factors, it is difficult to predict natural history of asthma
      in an individual child.

PMID- 11980467
TI  - Long-term management of asthma.
AB  - Long-term management of asthma includes identification and avoidance of
      precipitating factors of asthma, pharmacotherapy and home management plan. Common
      precipitating factors include viral upper respiratory infections, exposure to
      smoke, dust, cold food and cold air. Avoidance of common precipitating factors
      has been shown to help in better control of asthma. Pharmacotherapy is the main
      stay of treatment of asthma. Commonly used drugs for better control of asthma are
      long and short acting bronchodilators, mast cell stabilizers, inhaled steroids,
      theophylline and steroid sparing agents. After assessment of severity most
      appropriate medications are selected. For mild episodic asthma the medications
      are short acting beta agonists as and when required. For mild persistent asthma:
      as and when required bronchodilators along with a daily maintenance treatment in
      form of low dose inhaled steroids or cromolyn or oral theophylline or ketotifen
      are required. Moderate persistent asthma should be treated with inhaled steroids
      along with long acting beta agonists for symptom control. For severe persistent
      asthma the recommended treatment includes inhaled steroids, long acting beta
      agonists with or without theophylline. If symptoms are not well controlled, a
      minimal dose of oral prednisolone preferably on alternate days may be needed in
      few patients. Newer drugs like leukotriene antagonists may find a place in
      control of exercise-induced bronchoconstriction and mild and moderate persistent
      asthma. Patients should be followed up every 8-12 weeks. On each follow up visit
      patients should be examined by a doctor, compliance to medications should be
      checked and actual inhalation technique is observed. Depending on the assessment,
      medications may be decreased or stepped up. For exercise induced
      bronchoconstriction: cromolyn, short or long acting beta agonists may be used. In
      children with seasonal asthma, maintenance treatment according to assessed
      severity should be started 2 weeks in advance and continued throughout the
      season. These patients should be reassessed after discontinuing the treatment.
      Parents should be given a written plan for management of acute exacerbation at
      home.

PMID- 11980468
TI  - Difficult asthma.
AB  - Children with asthma who are not well controlled in spite of optimum therapy
      outlined in Asthma Management Guidelines are said to have 'difficult-to manage
      asthma' or 'difficult asthma'. Several phenotypes of this subset of asthma have
      been described. However, before any child is labeled as difficult asthma a
      thorough search for an alternative diagnosis should be made. Thus, one should
      look for recurrent aspiration pneumonia, tuberculosis, foreign body aspiration,
      tracheomalacia, bronchomalacia, cystic fibrosis etc. Causes of treatment failure
      range from unidentified exacerbating factors, noncompliance, inappropriate
      inhalers and spacers and true steroid dependence or resistance. Economics of the
      treatment and social beliefs should also be taken into consideration at the time
      of finalizing the management plan. Management involves recognizing and correcting
      the above factors. However, steroids form the main pillar of treatment. Majority
      of the patients can be controlled by optimizing inhaled steroid therapy and
      possibly adding steroid sparing agents. Thus, long acting bata-2 agonists, long
      acting theophyllines and leukotriene inhibiters may be useful. A few children
      will require continuous oral steroid therapy and an occasional one may be
      actually steroid steroid resistant. Such children are best managed at asthma
      specialist centers where experimental drugs like, methotrexate cyclosporin or
      IVIG may be tried on an individual basis under close monitoring.

PMID- 11980469
TI  - Psychosocial issues in the management and treatment of children and adolescents
      with asthma.
AB  - Asthma is one of the most common chronic childhood illness. Studies have reported
      higher incidence of psychosocial adaptation problems in children with asthma,
      particularly severe asthma, than children in the general population. Increased
      psychosocial problems in children with asthma have been ascribed to adverse
      developmental impact of having a chronic health problems, increased demands on
      the family and dysfunctional familial interactional patterns. Treatment models
      include education and self management training programs, family therapy,
      relaxation therapy and biofeedback. These programs have been found to produce
      improved adjustment, increased medication compliance and greater perceived self
      competence in managing symptoms and decreased use of medical services. It is
      concluded that children with asthma require a comprehensive management strategy
      that pays attention not only to physiological control of asthma symptoms but also
      emotional and behavioural problems of children and their families.

PMID- 11980470
TI  - Importance of patient/parents education in childhood asthma.
AB  - Asthma is fairly common in pediatric age group and the suffering due to asthma
      continues to increase despite excellent treatments available. One of the four
      major components of asthma management is patient education and is critical to the
      success of asthma management. Reasons for continued suffering include that our
      management strategies are not easily understood by the patient/parents without a
      simple and careful approach towards this step. Eliciting common concerns and
      fears is the single and foremost strategy to develop a relationship of trust with
      the patients/parents. Making them understand about the chronic nature of asthma,
      need for a long-term care approach, what happens during acute attacks and where
      medications act are some of the important areas you should be educating about in
      the beginning. Then comes the skill transfer, i.e. giving them skills to monitor
      asthma including use of peakflowmeter and use of inhalation devices effectively.
      Joint development of written plans for medications is essential. Development of
      plans to control of asthma; jointly with them; including learning about warning
      signs and a plan to manage acute attack at home is also very important and
      patient/parents should be having an active participation. Finally, educating them
      how to identify asthma triggers helps as a long-term strategy to keep control
      over asthma with or without medications. Reminding patient/parents when to come
      for follow-up and what would be discussed next time are some important tricks of
      the trade.

PMID- 11980471
TI  - Diagnosis and monitoring of childhood asthma.
AB  - Diagnosis of asthma is clinical, however due to varied presentations in childhood
      both under and over diagnosis are possible. A good number of cases may not
      present with wheeze but may have a cough variant asthma. Episodic symptoms of
      airflow obstruction and reversibility are two very important features of asthma.
      Many congenital (Cystic fibrosis) and acquired conditions (foreign body) may
      cause wheezing in childhood and should be ruled out clinically or by specific
      investigations. Spirometry and peak expiratory flow rates help in objective
      assessment and are good tools for monitoring chronic patients. Total IgE has no
      role in diagnosis. There is now emphasis on co-management of asthma and
      patient/parents should be trained to keep symptoms records and wherever possible
      peak flow records. They should also be taught proper interpretation of readings
      for stepping up therapy in case of worsening.

PMID- 11980472
TI  - Bibliography of food microbiology.

PMID- 11980473
TI  - Resonance Raman detection of the Fe-S bond in endothelial nitric oxide synthase.
AB  - We report the first low-frequency resonance Raman spectra of ferric endothelial
      nitric oxide synthase (eNOS) holoenzyme, including the frequency of the Fe-S
      vibration in the presence of the substrate L-arginine. This is the first direct
      measurement of the strength of the Fe-S bond in NOS. The Fe-S vibration is
      observed at 338 cm(-1) with excitation at 363.8 nm. The assignment of this band
      to the Fe-S stretching vibration was confirmed by the observation of isotopic
      shifts in eNOS reconstituted with 54Fe- and 57Fe-labeled hemin. Furthermore, the
      frequency of this vibration is close to those observed in cytochrome P450(cam)
      and chloroperoxidase (CPO). The frequency of this vibration is lower in eNOS than
      in P450(cam) and CPO, which can be explained by differences in hydrogen bonding
      to the proximal cysteine heme ligand. On addition of substrate to eNOS, we also
      observe several low-frequency vibrations, which are associated with the heme
      pyrrole groups. The enhancement of these vibrations suggests that substrate
      binding results in protein-mediated changes of the heme geometry, which may
      provide the protein with an additional tuning element for the redox potential of
      the heme iron. The implications of our findings for the function of eNOS will be
      discussed by comparison with P450(cam) and model compounds.

PMID- 11980474
TI  - Photolabeling identifies an interaction between phosphatidylcholine and glycerol
      3-phosphate dehydrogenase (Gut2p) in yeast mitochondria.
AB  - In search of mitochondrial proteins interacting with phosphatidylcholine (PC), a
      photolabeling approach was applied, in which photoactivatable probes were
      incorporated into isolated yeast mitochondria. Only a limited number of proteins
      were labeled upon photoactivation, using either the PC analogue [125I]TID-PC or
      the small hydrophobic probe [125I]TID-BE. The most prominent difference was the
      very specific labeling of a 70 kDa protein by [125I]TID-PC. Mass spectrometric
      analysis of a tryptic digest of the corresponding 2D-gel spot identified the
      protein as the GUT2 gene product, the FAD-dependent mitochondrial glycerol-3
      phosphate dehydrogenase. This was confirmed by the lack of specific labeling in
      mitochondria from a gut2 deletion strain. Only under conditions where the inner
      membrane was accessible to the probe, Gut2p was labeled by [125I]TID-PC, in
      parallel with increased labeling of the phosphate carrier (P(i)C) in the inner
      membrane. A hemagglutinin-tagged version of Gut2p was shown to be membrane-bound.
      Carbonate extraction released the protein from the membrane, whereas a high
      concentration of NaCl did not, demonstrating that Gut2p is a peripheral membrane
      protein bound to the inner membrane via hydrophobic interactions. The
      significance of the observed interactions between Gut2p and PC is discussed.

PMID- 11980475
TI  - The solution structure of the CBM4-2 carbohydrate binding module from a
      thermostable Rhodothermus marinus xylanase.
AB  - The solution structure is presented for the second family 4 carbohydrate binding
      module (CBM4-2) of xylanase 10A from the thermophilic bacterium Rhodothermus
      marinus. CBM4-2, which binds xylan tightly, has a beta-sandwich structure formed
      by 11 strands, and contains a prominent cleft. From NMR titrations, it is shown
      that the cleft is the binding site for xylan, and that the main amino acids
      interacting with xylan are Asn31, Tyr69, Glu72, Phe110, Arg115, and His146. Key
      liganding residues are Tyr69 and Phe110, which form stacking interactions with
      the sugar. It is suggested that the loops on which the rings are displayed can
      alter their conformation on substrate binding, which may have functional
      importance. Comparison both with other family 4 cellulose binding modules and
      with the structurally similar family 22 xylan binding module shows that the key
      aromatic residues are in similar positions, and that the bottom of the cleft is
      much more hydrophobic in the cellulose binding modules than the xylan binding
      proteins. It is concluded that substrate specificity is determined by a
      combination of ring orientation and the nature of the residues lining the bottom
      of the binding cleft.

PMID- 11980476
TI  - Calcium binding and thermostability of carbohydrate binding module CBM4-2 of
      Xyn10A from Rhodothermus marinus.
AB  - Calcium binding to carbohydrate binding module CBM4-2 of xylanase 10A (Xyn10A)
      from Rhodothermus marinus was explored using calorimetry, NMR, fluorescence, and
      absorbance spectroscopy. CBM4-2 binds two calcium ions, one with moderate
      affinity and one with extremely high affinity. The moderate-affinity site has an
      association constant of (1.3 +/- 0.3) x 10(5) M(-1) and a binding enthalpy
      DeltaH(a) of -9.3 +/- 0.4 kJ x mol(-1), while the high-affinity site has an
      association constant of approximately 10(10) M(-1) and a binding enthalpy
      DeltaH(a) of -40.5 +/- 0.5 kJ x mol(-1). The locations of the binding sites have
      been identified by NMR and structural homology, and were verified by site
      directed mutagenesis. The high-affinity site consists of the side chains of E11
      and D160 and backbone carbonyls of E52 and K55, while the moderate-affinity site
      comprises the side chain of D29 and backbone carbonyls of L21, A22, V25, and W28.
      The high-affinity site is in a position analogous to the calcium site in CBM4
      structures and in a recent CBM22 structure. Binding of calcium increases the
      unfolding temperature of the protein (T(m)) by approximately 23 degrees C at pH
      7.5. No correlation between binding affinity and T(m) change was noted, as each
      of the two calcium ions contributes almost equally to the increase in unfolding
      temperature.

PMID- 11980477
TI  - Structure of the beta subunit of translation initiation factor 2 from the
      archaeon Methanococcus jannaschii: a representative of the eIF2beta/eIF5 family
      of proteins.
AB  - The beta subunit of archaeal translation initiation factor 2 (aIF2beta) is a
      representative of a family of proteins whose members include the beta subunit of
      eukaryotic translation initiation factor 2 (eIF2beta) and the N-terminal domain
      within translation initiation factor 5 (eIF5); no members of this family of
      proteins have been structurally characterized up to this time. In the work
      presented here, aIF2beta from Methanococcus jannaschii was expressed in
      Escherichia coli, purified, and analyzed using multidimensional NMR methods. The
      aIF2beta was found to contain two independent structural domains. The N-terminal
      domain contains a four-stranded antiparallel beta sheet and two alpha helices,
      and is structurally similar to the DNA-binding domain of a yeast heat shock
      transcription factor and a domain within ribosomal protein S4. This structural
      similarity was an unanticipated result, since no significant homology was
      detected at the level of primary sequence. The C-terminal domain of aIF2beta
      contains a zinc-binding motif of three antiparallel beta strands, with four
      conserved cysteines arranged as two CXXC units separated by 17 residues.
      Conserved residues on the surface of each domain that are likely candidates for
      direct interaction with other components of the translational apparatus were
      identified. The significant primary sequence homology between archaeal aIF2beta
      and the eukaryotic eIF2beta and eIF5, when combined with the structural results
      in the work presented here, permitted structural features to be predicted for
      these latter two eukaryotic proteins.

PMID- 11980478
TI  - Equilibrium unfolding of the C-terminal SAM domain of p73.
AB  - The sterile alpha motif (SAM) domain is a protein module of approximately 65 to
      70 amino acids found in many diverse proteins whose functions range from signal
      transduction to transcriptional repression. The alpha splice variant of p73 (p73
      alpha), a homologue of the tumor suppressor p53, has close to its C-terminus a
      SAM motif. Here, we report the folding equilibrium properties of the p73 alpha
      SAM domain (SAMp73) by using different biophysical techniques (circular
      dichroism, fluorescence, and Fourier transform infrared spectroscopies, and
      differential scanning calorimetry). Those probes indicate that SAMp73 folds via a
      two-state mechanism. Fluorescence experiments performed at different pHs showed
      two titrations: the first one due to an acid residue (with a pK(a) = 4.5 +/- 0.3)
      and the second due to deprotonation of tyrosine residues. The conformational
      stability of the protein upon chemical denaturation was determined over the pH
      range 3 to 10. The maximum conformational stability is DeltaG = 5.7 +/- 0.4 kcal
      x mol(-1) (at 25 degrees C) and occurs in a broad maximum, with little variation,
      between pH 6 and 10. The high melting temperature of SAMp73 (T(m) = 93.5 degrees
      C), despite its moderate conformational stability at 25 degrees C, can be
      ascribed to its low heat capacity change upon unfolding, DeltaC(p), which is
      estimated to be around 915 cal x K(-1) x mol(-1) at 25 degrees C and only around
      543 cal x K(-1) x mol(-1) at the T(m). The implications of the temperature
      dependent nature of DeltaC(p) are discussed in relation to the thermal stability
      of proteins as opposed to their conformational stability at room temperature.

PMID- 11980479
TI  - Connexin family members target to lipid raft domains and interact with caveolin
      1.
AB  - Lipid rafts are cholesterol-sphingolipid-rich microdomains that function as
      platforms for membrane trafficking and signal transduction. Caveolae are
      specialized lipid raft domains that contain the structural proteins known as the
      caveolins. Connexins are a family of transmembrane proteins that self-associate
      to form cell-cell connections known as gap junctions and that are linked to
      cytosolic proteins, forming a protein complex or Nexus. To determine the extent
      to which these intracellular compartments intersect, we have systematically
      evaluated whether connexins are associated with lipid rafts and caveolin-1. We
      show that connexin 43 (Cx43) colocalizes, cofractionates, and
      coimmunoprecipitates with caveolin-1. A mutational analysis of Cx43 reveals that
      the hypothesized PDZ- and presumptive SH2/SH3-binding domains within the Cx43
      carboxyl terminus are not required for this targeting event or for its stable
      interaction with caveolin-1. Furthermore, Cx43 appears to interact with two
      distinct caveolin-1 domains, i.e., the caveolin-scaffolding domain (residues 82
      101) and the C-terminal domain (135-178). We also show that other connexins
      (Cx32, Cx36, and Cx46) are targeted to lipid rafts, while Cx26 and Cx50 are
      specifically excluded from these membrane microdomains. Interestingly,
      recombinant coexpression of Cx26 with caveolin-1 recruits Cx26 to lipid rafts,
      where it colocalizes with caveolin-1. This trafficking event appears to be unique
      to Cx26, since the other connexins investigated in this study do not require
      caveolin-1 for targeting to lipid rafts. Our results provide the first evidence
      that connexins interact with caveolins and partition into lipid raft domains and
      indicate that these interactions are connexin specific.

PMID- 11980480
TI  - Mapping the G-actin binding surface of cofilin using synchrotron protein
      footprinting.
AB  - Cofilin is an actin regulatory protein that binds to both monomeric and
      filamentous actin, and has filament severing activity. Although crystal
      structures for the monomeric forms of both G-actin and cofilin have been
      described, the structure of the binary cofilin-G-actin complex is not available.
      Synchrotron protein footprinting is used to identify specific side chain residues
      on the cofilin surface that are buried in the formation of the cofilin-G-actin
      binary complex. Exposure to synchrotron X-rays results in stable oxidative
      modifications of aromatic, aliphatic, and sulfur-containing side chains, with the
      rate of modification for a particular residue being dependent on its intrinsic
      reactivity and solvent accessibility. The rates of modification were monitored
      for a number of peptides generated by digestion of oxidized cofilin, both in
      isolation and in its binary complex with G-actin. After binding to G-actin takes
      place, a significant decrease in modification rates, indicating protection of
      side chain groups, is seen for cofilin peptides corresponding to residues 4-20,
      10-17, 83-96, 91-105, and 106-117. A number of other peptides show no change in
      reactivity, and are presumed to represent regions distal to the binding site.
      Tandem mass spectrometry demonstrates that residues Leu 13, Pro 94, Met 99, and
      Leu 108 and 112 directly participate in the binding interface. These results are
      generally consistent with, and complementary to, the results of previous site
      directed mutagenesis studies and extend our understanding of the G-actin binding
      surface of cofilin.

PMID- 11980481
TI  - Structure and calcium-binding studies of a recoverin mutant (E85Q) in an
      allosteric intermediate state.
AB  - Recoverin, a member of the EF-hand superfamily, serves as a calcium sensor in
      retinal rod cells. A myristoyl or related fatty acyl group covalently attached to
      the N-terminus of recoverin facilitates the binding of recoverin to retinal disk
      membranes by a mechanism known as the Ca2+-myristoyl switch. Previous structural
      studies revealed that the myristoyl group of recoverin is sequestered inside the
      protein core in the absence of calcium. The cooperative binding of two calcium
      ions to the second and third EF-hands (EF-2 and EF-3) of recoverin leads to the
      extrusion of the fatty acid. Here we present nuclear magnetic resonance (NMR),
      fluorescence, and calcium-binding studies of a myristoylated recoverin mutant
      (myr-E85Q) designed to abolish high-affinity calcium binding to EF-2 and thereby
      trap the myristoylated protein with calcium bound solely to EF-3. Equilibrium
      calcium-binding studies confirm that only one Ca2+ binds to myr-E85Q under the
      conditions of this study with a dissociation constant of 100 microM. Fluorescence
      and NMR spectra of the Ca2+-free myr-E85Q are identical to those of Ca2+-free
      wild type, indicating that the E85Q mutation does not alter the stability and
      structure of the Ca2+-free protein. In contrast, the fluorescence and NMR spectra
      of half-saturated myr-E85Q (one bound Ca2+) look different from those of Ca2+
      saturated wild type (two bound Ca2+), suggesting that half-saturated myr-E85Q may
      represent a structural intermediate. We report here the three-dimensional
      structure of Ca2+-bound myr-E85Q as determined by NMR spectroscopy. The N
      terminal myristoyl group of Ca2+-bound myr-E85Q is sequestered within a
      hydrophobic cavity lined by many aromatic residues (F23, W31, Y53, F56, F83, and
      Y86) resembling that of Ca2+-free recoverin. The structure of Ca2+-bound myr-E85Q
      in the N-terminal region (residues 2-90) is similar to that of Ca2+-free
      recoverin, whereas the C-terminal region (residues 100-202) is more similar to
      that of Ca2+-bound wild type. Hence, the structure of Ca2+-bound myr-E85Q
      represents a hybrid between the structures of recoverin with zero and two Ca2+
      bound. The binding of Ca2+ to EF-3 leads to local structural changes within the
      EF-hand that alter the domain interface and cause a 45 degrees swiveling of the N
      and C-terminal domains, resulting in a partial unclamping of the myristoyl
      group. We propose that Ca2+-bound myr-E85Q may represent a stable intermediate
      state in the kinetic mechanism of the calcium-myristoyl switch.

PMID- 11980482
TI  - Subunit exchange and the role of dimer flexibility in DNA binding by the Fis
      protein.
AB  - Fis is an abundant bacterial DNA binding protein that functions in many different
      reactions. We show here that Fis subunits rapidly exchange between dimers in
      solution by disulfide cross-linking mixtures of Fis mutants with different
      electrophoretic mobilities and by monitoring energy transfer between
      fluorescently labeled Fis subunits upon heterodimer formation. The effects of
      detergents and salt concentrations on subunit exchange imply that the dimer is
      predominantly stabilized by hydrophobic forces, consistent with the X-ray crystal
      structures. Specific and nonspecific DNA strongly inhibit Fis subunit exchange.
      In all crystal forms of Fis, the separation between the DNA recognition helices
      within the Fis dimer is too short to insert into adjacent major grooves on
      canonical B-DNA, implying that conformational changes within the Fis dimer and/or
      the DNA must occur upon binding. We therefore investigated the functional
      importance of dimer interface flexibility for Fis-DNA binding by studying the DNA
      binding properties of Fis mutants that were cross-linked at different positions
      in the dimer. Flexibility within the core dimer interface does not appear to be
      required for efficient DNA binding, Fis-DNA complex dissociation, or Fis-induced
      DNA bending. Moreover, FRET-based experiments provided no evidence for a change
      in the spatial relationship between the two helix-turn-helix motifs in the Fis
      dimer upon DNA binding. These results support a model in which the unusually
      short distance between DNA recognition helices on Fis is accommodated primarily
      through bending of the DNA.

PMID- 11980483
TI  - Linkage of monovalent and divalent ion binding in the folding of the P4-P6 domain
      of the Tetrahymena ribozyme.
AB  - We have explored the linkage of monovalent and divalent ion binding in the
      folding of the P4-P6 domain of Tetrahymena thermophila ribozyme by examining the
      Mg2+-induced folding and the urea-induced denaturation of the folded state as a
      function of Na+ under equilibrium folding conditions using hydroxyl radical
      footprinting. These studies allowed a thermodynamic examination of eight discrete
      protection sites within P4-P6 that are involved in several tertiary structure
      contacts. Monovalent ions compete with Mg2+ ions in mediating P4-P6 folding. The
      urea denaturation isotherms demonstrated DeltaDeltaG values of >2 kcal x mol(-1)
      in experiments conducted in 10 versus 200 mM NaCl at a constant 10 mM MgCl2.
      However, the individual-site isotherms reported by footprinting revealed that
      larger than average changes in DeltaG values were localized to specific sites
      within the Mg2+-rich A-bulge. The competitive effects of monovalent ions were
      less when K+ rather than Na+ was the monovalent cation present. This result
      indicates the importance of the specific K+ binding sites that are associated
      with AA-platform structures to P4-P6 folding and stability. These site-specific
      footprinting data provide quantitative and site-specific measurements of the ion
      linked stability for P4-P6 that are interpreted with respect to crystallographic
      data.

PMID- 11980484
TI  - Double mutant studies identify electrostatic interactions that are important for
      docking cytochrome c2 onto the bacterial reaction center.
AB  - Cytochrome c2 (cyt) is the mobile electron donor to the reaction center (RC) in
      photosynthetic bacteria. The electrostatic interactions involved in the dynamics
      of docking of cyt onto the RC were examined by double mutant studies of the rates
      of electron transfer between six modified Rhodobacter sphaeroides RCs in which
      negatively charged acid residues were replaced with Lys and five modified
      Rhodobacter capsulatus Cyt c2 molecules in which positively charged Lys residues
      were replaced with Glu. We measured the second-order rate constant, k2, for
      electron transfer from the reduced cyt to the oxidized primary donor on the RC,
      which reflects the energy of the transition state for the formation of the active
      electron transfer complex. Strong interactions were found between Lys C99 and Asp
      M184/Glu M95, and between Lys C54 and Asp L261/Asp L257. The interacting residues
      were found to be located close to each other in the recently determined crystal
      structure of the cyt-RC complex [Axelrod, H., et al. (2002) J. Mol. Biol. (in
      press)]. The interaction energies were approximately inversely proportional to
      the distances between charges. These results support earlier suggestions
      [Tetreault, M., et al. (2001) Biochemistry 40, 8452-8462] that the structure of
      the transition state in solution resembles the structure of the cyt-RC complex in
      the cocrystal and indicate that specific electrostatic interactions facilitate
      docking of the cyt onto the RC in a configuration optimized for both binding and
      electron transfer. The specific interaction between Asp M184 and Lys C99 may help
      to nucleate short-range hydrophobic contacts.

PMID- 11980485
TI  - Effect of solution viscosity on intramolecular electron transfer in sulfite
      oxidase.
AB  - Our previous studies have shown that the rate constant for intramolecular
      electron transfer (IET) between the heme and molybdenum centers of chicken liver
      sulfite oxidase varies from approximately 20 to 1400 s(-1) depending upon
      reaction conditions [Pacheco, A., Hazzard, J. T., Tollin, G., and Enemark, J. H.
      (1999) J. Biol. Inorg. Chem. 4, 390-401]. These two centers are linked by a
      flexible polypeptide loop, suggesting that conformational changes, which alter
      the Mo-Fe distance, may play an important role in the observed IET rates. In this
      study, we have investigated IET in sulfite oxidase using laser flash photolysis
      as a function of solution viscosity. The solution viscosity was varied over the
      range of 1.0-2.0 cP by addition of either polyethylene glycol 400 or sucrose. In
      the presence of either viscosogen, an appreciable decrease in the IET rate
      constant value is observed with an increase in the solvent viscosity. The IET
      rate constant exhibits a linear dependence on the negative 0.7th power of the
      viscosity. Steady-state kinetics and EPR experiments are consistent with the
      interpretation that viscosity, and not other properties of the added viscosogens,
      is responsible for the dependence of IET rates on the solvent composition. The
      results are consistent with the role of conformational changes on IET in sulfite
      oxidase, which helps to clarify the inconsistency between the large rate constant
      for IET between the Mo and Fe centers and the long distance (approximately 32 A)
      between these two metal centers observed in the crystal structure [Kisker, C.,
      Schindelin, H., Pacheco, A., Wehbi, W., Garnett, R. M., Rajagopalan, K. V.,
      Enemark, J. H., and Rees, D. C. (1997) Cell 91, 973-983].

PMID- 11980486
TI  - Copper transfer from the Cu(I) chaperone, CopZ, to the repressor, Zn(II)CopY:
      metal coordination environments and protein interactions.
AB  - Extracellular copper regulates the DNA binding activity of the CopY repressor of
      Enterococcus hirae and thereby controls expression of the copper homeostatic
      genes encoded by the cop operon. CopY has a CxCxxxxCxC metal binding motif. CopZ,
      a copper chaperone belonging to a family of metallochaperones characterized by a
      MxCxxC metal binding motif, transfers copper to CopY. The copper binding
      stoichiometries of CopZ and CopY were determined by in vitro metal
      reconstitutions. The stoichiometries were found to be one copper(I) per CopZ and
      two copper(I) per CopY monomer. X-ray absorption studies suggested a mixture of
      two- and three-coordinate copper in Cu(I)CopZ, but a purely three-coordinate
      copper coordination with a Cu-Cu interaction for Cu(I)2CopY. The latter
      coordination is consistent with the formation of a compact binuclear Cu(I)
      thiolate core in the CxCxxxxCxC binding motif of CopY. Displacement of zinc, by
      copper, from CopY was monitored with 2,4-pyridylazoresorcinol. Two copper(I) ions
      were required to release the single zinc(II) ion bound per CopY monomer. The
      specificity of copper transfer between CopZ and CopY was dependent on
      electrostatic interactions. Relative copper binding affinities of the proteins
      were investigated using the chelator, diethyldithiocarbamic acid (DDC). These
      data suggest that CopY has a higher affinity for copper than CopZ. However, this
      affinity difference is not the sole factor in the copper exchange; a charge-based
      interaction between the two proteins is required for the transfer reaction to
      proceed. Gain-of-function mutation of a CopZ homologue demonstrated the necessity
      of four lysine residues on the chaperone for the interaction with CopY. Taken
      together, these results suggest a mechanism for copper exchange between CopZ and
      CopY.

PMID- 11980487
TI  - pH dependence of the four individual transitions in the catalytic S-cycle during
      photosynthetic oxygen evolution.
AB  - We have investigated the pH dependence for each individual redox transition in
      the S-cycle of the oxygen evolving complex (OEC) of photosystem II by electron
      paramagnetic resonance (EPR) spectroscopy. In the experiments, OEC is advanced to
      the appropriate S-state at normal pH. Then, the pH is rapidly changed, and a new
      flash is given. The ability to advance to the next S-state in the cycle at
      different pHs is determined by measurements of the decrease or increase of
      characteristic EPR signals from the OEC in different S-states. In some cases the
      measured EPR signals are very small (this holds especially for the S0 ML signal
      at pH >7.5 and pH <4.8). Therefore, we refrain from providing error limits for
      the determined pK's. Our results indicate that the S1 --> S2 transition is
      independent of pH between 4.1 and 8.4. All other S-transitions are blocked at low
      pH. In the acidic region, the pK's for the inhibition of the S2 --> S3, the S3 -
      > [S4] --> S0, and the S0 --> S1 transitions are about 4.0, 4.5, and 4.7,
      respectively. The similarity of these pK values indicates that the inhibition of
      the steady-state oxygen evolution in the acidic range, which occurs with pK
      approximately 4.8, is a consequence of similar pH blocks in three of the redox
      steps involved in the oxygen evolution. In the alkaline region, we report a clear
      pH block in the S3 --> [S4] --> S0 transition with a pK of about 8.0. Our study
      also indicates the existence of a pH block at very high pH (pK approximately 9.4)
      in the S2 --> S3 transition. The S0 --> S1 transition is not affected, at least
      up to pH 9.0. This suggests that the inhibition of the steady-state oxygen
      evolution, which occurs with a pK of 8.0, is dominated by the inhibition of the
      S3 --> [S4] --> S0 transition. Our results are obtained in the presence of 5%
      methanol (v/v). However, it is unlikely that the determined pK's are affected by
      the presence of methanol since our results also show that the pH dependence of
      the steady-state oxygen evolution is not affected by methanol. The results in the
      alkaline region are in good agreement with a model, which suggests that the redox
      potential of Y(Z*)/Y(Z) is directly affected by high pH. At high pH the
      Y(Z*)/Y(Z) potential becomes lower than that of S2/S1 and S3/S2. The acidic
      block, with a pK of 4-5 in three S-transitions, implies that the inhibition
      mechanism is similar, and we suggest that it reflects protonation of a carboxylic
      side chain in the proton relay that expels protons from the OEC.

PMID- 11980488
TI  - Characteristic changes of the S2/S1 difference FTIR spectrum induced by Ca2+
      depletion and metal cation substitution in the photosynthetic oxygen-evolving
      complex.
AB  - Effects of Ca2+ depletion and substitution with other metal cations on the
      structure of the protein matrices of the oxygen-evolving complex (OEC) and their
      corresponding changes upon the S1 to S2 transition were examined using Fourier
      transform infrared (FTIR) spectroscopy. Ca2+ depletion and further
      supplementation with Li+, Na+, Mg2+, Ca2+, or Sr2+ did not significantly affect
      the typical vibrational features in the double difference S2/S1 spectrum,
      including the symmetric [1365(+)/1404(-) cm(-1)] and the asymmetric
      [1587(+)/1566(-) cm(-1)] stretching modes of the carboxylate ligand and the amide
      I and II modes of the backbone polypeptides. On the other hand, supplementation
      with K+, Rb+, Cs+, or Ba2+ significantly modified the S2/S1 spectrum, in which
      the carboxylate modes disappeared and the amide I and II modes were modified.
      Results indicate that the binding of metal cations that have ionic radii larger
      than that of Ca2+ to the Ca2+ site induces perturbations in the protein matrices
      in the vicinity of the Mn cluster to interrupt the characteristic structural
      and/or conformational changes upon the oxidation of the Mn cluster accompanied
      with the S1 to S2 transition. The spectrum was also altered by the
      supplementation of Cd2+, which has an ionic radius comparable to that of Ca2+. A
      single-pulse-induced S2/S1 difference spectrum revealed that bands that have been
      assigned to the vibrational modes for the Y(Z) tyrosine and the histidine ligand
      for the Mn cluster were not induced in the K+-supplemented membranes, although
      the histidine band is likely to be preserved in the Ca2+-depleted membranes. The
      Y(Z) band was considerably small in the double difference S2/S1 spectrum in the
      Ca2+-depleted and the cation-substituted membranes but distinctively present in
      the Sr2+- or Ca2+-replenished membranes. Furthermore, cation supplementation
      induced several new bands that disappeared following the Ca2+ replenishment.
      These results suggest that the proper organization of the hydrogen bond network
      within OEC for the water oxidation chemistry requires the Ca2+ ion and indicate
      that the role of Ca2+ is not purely structurally defined by the physical
      properties of the ion, such as valence and ionic radius. On the basis of these
      and other findings, we propose that Ca2+ is necessary for the formation of the
      hydrogen bond network that is involved in the reaction step of water oxidation.

PMID- 11980489
TI  - Blocking of electron donation by Mn(II) to Y(Z*) following incubation of Mn
      depleted photosystem II membranes with Fe(II) in the light.
AB  - The donation of electrons by Mn(II) and Fe(II) to Y(Z*) through the high-affinity
      (HA(Z)) site in Mn-depleted photosystem II (PSII) membranes has been studied by
      flash-probe fluorescence yield measurements. Mn(II) and Fe(II) donate electrons
      to Y(Z*) with about the same efficiency, saturating this reaction at the same
      concentration (ca. 5 microM). However, following a short incubation of the
      membranes with 5 microM Fe(II), but not with Mn(II) in room light, added Mn(II)
      or Fe(II) can no longer be photooxidized by Y(Z)(*). This blocking effect is
      caused by specifically bound, photooxidized Fe [> or =Fe(III)] and is accompanied
      by a delay in the fluorescence yield decay kinetics attributed to the slowing
      down of the charge recombination rate between Q(a-) and Y(Z*). Exogenously added
      Fe(III), on the other hand, does not donate electrons to Y(Z*), does not block
      the donation of electrons by added Mn(II) and Fe(II), and does not change the
      kinetics of the decay of the fluorescence yield. These results demonstrate that
      the light-dependent oxidation of Fe(II) by Y(Z*) creates an Fe species that binds
      at the HA(Z) site and causes the blocking effect. The pH dependence of Mn(II)
      electron donation to Y(Z*) via the HA(Z) site and of the Fe-blocking effect is
      different. These results, together with sequence homologies between the C
      terminal ends of the D1 and D2 polypeptides of the PSII reaction center and
      several diiron-oxo enzymes, suggest the involvement of two or perhaps more (to an
      upper limit of four to five) bound iron cations per reaction center of PSII in
      the blocking effect. Similarities in the interaction of Fe(II) and Mn(II) with
      the HA(Z) Mn site of PSII during the initial steps of the photoactivation process
      are discussed. The Fe-blocking effect was also used to investigate the
      relationship between the HA(Z) Mn site and the HA sites on PSII for
      diphenylcarbazide (DPC) and NH2OH oxidation. Blocking of the HA(Z) site with
      specifically bound Fe leads to the total inhibition of electron donation to Y(Z*)
      by DPC. Since DPC and Mn(II) donation to PSII is noncompetitive [Preston, C., and
      Seibert, M. (1991) Biochemistry 30, 9615-9624], the Fe bound to the HA(Z) site
      can also block the DPC donation site. On the other hand, electron donation by
      NH2OH to PSII still occurs in Fe-blocked membranes. Since hydroxylamine does not
      reduce the Fe [> or =Fe(III)] specifically bound to the HA(Z) site, NH2OH must
      donate to Y(Z*) through its own site or directly to P680+.

PMID- 11980490
TI  - Is the PTPase-vanadate complex a true transition state analogue?
AB  - Vanadate can often bind to phosphoryl transfer enzymes to form a trigonal
      bipyramidal structure at the active site. The enzyme-vanadate dissociation
      constants in these enzymes are much lower than those for phosphate. Therefore,
      enzyme-bound vanadate moieties are often considered as transition state
      analogues. To test whether the enzyme-vanadate complex is a true transition state
      analogue beyond the simple geometry and binding affinity arguments and whether
      the bond orders of the VO bonds in the complex approach those of the PO bonds in
      the transition state, the binding properties of vanadate in the Yersinia protein
      tyrosine phosphatase (PTPase) and its T410A, D356N, W354A, R409K, and D356A
      mutants have been studied by steady-state kinetic measurements and by difference
      Raman measurements. The results of the kinetic measurements show no correlation
      between K(I) and kcat or kcat/K(m) in these mutants. In addition, our analysis of
      the Raman data shows that the bond order change of the nonbridging V--O bonds in
      the vanadate complexes does not correlate with the kinetic parameters in a number
      of PTPase variants as predicted by the transition state binding paradigm.
      Furthermore, the ionization state of the bound vanadate moiety is not invariant
      across the PTPase variants studied, and the average bond order of the nonbridging
      V--O bonds decreased by 0.06-0.07 valence unit in the wild type and all of the
      mutant PTPases, either in dianionic or in monoanionic form. Thus the complex
      would resemble an associative transition state, contrary to the previously
      determined dissociative structure of the transition state. Therefore, it is
      concluded that vanadate is not a true transition state analogue for the PTPase
      reactions.

PMID- 11980491
TI  - Adenosine triphosphate-induced electron transfer in 2-hydroxyglutaryl-CoA
      dehydratase from Acidaminococcus fermentans.
AB  - 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans catalyzes the
      chemical difficult elimination of water from (R)-2-hydroxyglutaryl-CoA to
      glutaconyl-CoA. The enzyme consists of two oxygen-sensitive protein components,
      the homodimeric activator (A) with one [4Fe-4S]1+/2+ cluster and the
      heterodimeric dehydratase (D) with one nonreducible [4Fe-4S]2+ cluster and
      reduced riboflavin 5'-monophosphate (FMNH2). For activation, ATP, Mg2+, and a
      reduced flavodoxin (16 kDa) purified from A. fermentans are required. The [4Fe
      4S](1+/2+) cluster of component A is exposed to the solvent since it is
      accessible to iron chelators. Upon exchange of the bound ADP by ATP, the
      chelation rate is 8-fold enhanced, indicating a large conformational change.
      Oxidized component A exhibits ATPase activity of 6 s(-1), which is completely
      abolished upon reduction by one electron. UV-visible spectroscopy revealed a
      spontaneous one-electron transfer from flavodoxin hydroquinone (E(0)' = -430 mV)
      to oxidized component A, whereby the [4Fe-4S]2+ cluster of component A became
      reduced. Combined kinetic, EPR, and Mossbauer spectrocopic investigations
      exhibited an ATP-dependent oxidation of component A by component D. Whereas the
      [4Fe-4S]2+ cluster of component D remained in the oxidized state, a new EPR
      signal became visible attributed to a d1-metal species, probably Mo(V). Metal
      analysis with neutron activation and atomic absorption spectroscopy gave 0.07-0.2
      Mo per component D. In summary, the data suggest that in the presence of ATP one
      electron is transferred from flavodoxin hydroquinone via the [4Fe-4S]1+/2+
      cluster of component A to Mo(VI) of component D, which is thereby reduced to
      Mo(V). The latter may supply the electron necessary for transient charge reversal
      in the unusual dehydration.

PMID- 11980492
TI  - Apical loop-internal loop interactions: a new RNA-RNA recognition motif
      identified through in vitro selection against RNA hairpins of the hepatitis C
      virus mRNA.
AB  - We performed in vitro selection of oligoribonucleotides in order to identify high
      affinity motifs recognizing RNA hairpins located at the 3' end (SL1) and at the
      5' end (domain IV of the internal ribosome entry site) of the hepatitis C virus
      mRNA. We selected aptamers constituted by an internal loop complementary to the
      SL1 apical loop, flanked by G-C-rich double-stranded regions, able to form
      complexes with a K(d) of 70 nM, at 37 degrees C under ionic conditions close to
      intracellular ones. The complex involves selective apical loop (SL1)-internal
      loop (aptamer) interactions. Similar structurally organized aptamers were
      independently identified against domain IV and were shown to also give rise to
      such complexes. Apical loop-internal loop interaction could constitute a new
      recognition motif allowing specific intra- or intermolecular RNA-RNA association.

PMID- 11980493
TI  - Nontemplated nucleotide addition by HIV-1 reverse transcriptase.
AB  - We studied the kinetics of nontemplated nucleotide addition by the reverse
      transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) using model
      substrates derived from the 3' end of HIV-1 minus-strand strong-stop DNA. The
      addition of a nontemplated nucleotide was highly dependent on the nature of the
      base (fastest addition with dATP), type of nucleoside, and pH of the reaction
      buffer. The salt concentration, presence or absence of nucleocapsid protein, and
      nature of the blunt-ended duplex (DNA/DNA versus RNA/DNA) had only limited
      effects. The efficiency and base specificity were strongly affected by the
      sequence at the 3' end of the blunt-ended duplex. In every case, nontemplated
      nucleotide addition was much slower than templated polymerization. The K(d) for
      the incoming dNTP with an RT bound to a blunt-ended duplex was at least 1000-fold
      higher than with a duplex with a template overhang. At concentrations normally
      found in vivo, ATP can compete with dNTPs for binding to the polymerase active
      site and reduce the efficiency of nontemplated nucleotide addition. Although a
      stable ternary complex RT/DNA/dNTP could be readily detected by gel retardation
      assays if the DNA had a template overhang, stable ternary complexes were not
      observed with a blunt-ended duplex substrate. At in vivo concentrations of dNTPs
      (5-10 microM), nontemplated nucleotide addition occurred, but it was very
      inefficient and the rate of nontemplated polymerization is at least 10000-fold
      slower than the rate of templated polymerization. We could conclude that, in
      vivo, the unfavorable binding of the incoming dNTP, low concentration of dNTPs,
      the presence of a large concentration of ATP, and the inability to form a stable
      ternary complex prior to the polymerization step collaborate to reduce the
      efficiency of nontemplated nucleotide addition.

PMID- 11980494
TI  - Effects of chemical modification, tropomyosin, and myosin subfragment 1 on the
      yield strength and critical concentration of F-actin.
AB  - The effects of coupling with tetramethylrhodamine-5-iodoacetamide and of the
      decoration with tropomyosin and with myosin subfragment 1 on the elastic
      properties of F-actin filament are investigated. At 22 degrees C, in 15 mM
      orthophosphate and 3 mM MgCl2, tetramethylrhodamine F-actin displays a yield
      strength of 3.69 +/- 0.213 pN and an elastic modulus by stretching of 0.91 MPa.
      Decoration with tropomyosin increases the yield strength of tetramethylrhodamine
      F-actin to 10.51 +/- 0.24 pN and the elastic modulus by stretching to 23-75 MPa.
      Mixtures of myosin subfragment 1 and tetramethylrhodamine F-actin at the 0.2:1,
      0.4:1, 0.6:1, 0.8:1, and 1:1 molar ratios are also studied. Both yield strength
      and the elastic modulus by stretching are found to increase progressively with
      the ratio. At the 1:1 molar ratio, the yield strength is 15.81 +/- 0.26 pN and
      the elastic modulus by stretching is 13.45 to 40 MPa. Decoration of
      tetramethylrhodamine F-actin with both tropomyosin and myosin subfragment 1, at
      the 1:1 molar ratio with the actin monomer, produces filaments with an yield
      strength of 22.3 +/- 0.48 pN.

PMID- 11980495
TI  - Pyrene cholesterol reports the transient appearance of nonlamellar intermediate
      structures during fusion of model membranes.
AB  - We have hypothesized that modulating the free energy of hydrophobic mismatch (HM)
      might be a principal means to control the fusion process and that it may be a
      role of cholesterol to counteract HM and make membranes fusogenic. To test these
      hypotheses, we examined the ability of cholesterol 1-pyrenebutyrate (PY-Ch) and
      other pyrene-containing fluorescent probes to report interstices formed during
      the L(alpha)-H(II) transition of DiPoPE in terms of changes in excimer/monomer
      (E/M) fluorescence ratios. We found a significant (>150%) increase in the PY-Ch
      E/M in the hexagonal phase relative to the lamellar phase, presumably resulting
      from redistribution of PY-Ch from the curved lamellar leaflets to coexisting HMs
      that constitute 20 vol % of this phase. All other probes showed a much smaller or
      even an opposite (PY-hexadecanoic acid) effect. The time course of the PY-Ch E/M
      ratio during fusion of DOPC/PE/Ch small unilamellar vesicles showed a transient
      increase with a subsequent decrease, consistent with fusion proceeding through
      intermediates with significant HM. The amplitude and position of the maximum in
      E/M correlated with the rate of contents mixing. An increase in E/M was not seen
      when lipid mixing occurred in the absence of contents mixing. Our results suggest
      that PY-Ch provides a tool for monitoring fusion intermediates that occur after
      the initial fusion intermediate but prior to pore formation, possibly by
      accumulating in regions associated with HM.

PMID- 11980496
TI  - NMR analysis of the monomeric form of a mutant unliganded bovine neurophysin:
      comparison with the crystal structure of a neurophysin dimer.
AB  - Determination of the structure of the unliganded monomeric state of neurophysin
      is central to an understanding of the allosteric relationship between neurophysin
      peptide-binding and dimerization. We examined this state by NMR, using the weakly
      dimerizing H80E mutant of bovine neurophysin-I. The derived structure, to which
      more than one conformer appeared to contribute, was compared with the crystal
      structure of the unliganded des 1-6 bovine neurophysin-II dimer. Significant
      conformational differences between the two proteins were evident in the
      orientation of the 3,10 helix, in the 50-58 loop, in beta-turns, and in specific
      intrachain contacts between amino- and carboxyl domains. However, both had
      similar secondary structures, in independent confirmation of earlier circular
      dichroism studies. Previously suggested interactions between the amino terminus
      and the 50-58 loop in the monomer were also confirmed. Comparison of the observed
      differences between the two proteins with demonstrated effects of dimerization on
      the NMR spectrum of bovine neurophysin-I, and preliminary investigation of the
      effects of dimerization on H80E spectra, allowed tentative distinction between
      the contributions of sequence and self-association differences to the difference
      in conformation. Regions altered by dimerization encompass most binding site
      residues, providing a potential explanation of differences in binding affinity
      between the unliganded monomeric and dimeric states. Differences between monomer
      and dimer states in turns, interdomain contacts, and within the interdomain
      segment of the 50-58 loop suggest that the effects of dimerization on
      intrasubunit conformation reflect the need to adjust the relative positions of
      the interface segments of the two domains for optimal interaction with the
      adjacent subunit and/or reflect the dual role of some residues as participants
      both at the interface and in interdomain contacts.

PMID- 11980497
TI  - Covalent attachment of the heme prosthetic group in the CYP4F cytochrome P450
      family.
AB  - We demonstrated earlier that the heme in cytochrome P450 enzymes of the CYP4A
      family is covalently attached to the protein through an I-helix glutamic acid
      residue [Hoch, U., and Ortiz de Montellano, P. R. (2001) J. Biol. Chem. 276,
      11339-11346]. As the critical glutamic acid residue is conserved in many members
      of the CYP4F class of cytochrome P450 enzymes, we investigated covalent heme
      binding in this family of enzymes. Chromatographic analysis indicates that the
      heme is covalently bound in CYP4F1 and CYP4F4, which have the required glutamic
      acid residue, but not in CYP4F5 and CYP4F6, which do not. Catalytic turnover of
      CYP4F4 with NADPH-cytochrome P450 reductase shows that the heme is covalently
      bound through an autocatalytic process. Analysis of the prosthetic group in the
      CYP4F5 G330E mutant, into which the glutamic acid has been reintroduced, shows
      that the heme is partially covalently bound and partially converted to
      noncovalently bound 5-hydroxymethylheme. The modified heme presumably arises by
      trapping of a 5-methyl carbocation intermediate by a water molecule. CYP4F
      proteins thus autocatalytically bind their heme groups covalently in a process
      that requires a glutamic acid both to generate a reactive (cationic) form of the
      heme methyl and to trap it to give the ester bond.

PMID- 11980498
TI  - Dissociation of the GroEL-GroES asymmetric complex is accelerated by increased
      cooperativity in ATP binding to the GroEL ring distal to GroES.
AB  - A kinetic analysis of the ATP-dependent dissociation of wild-type GroEL and
      mutants from immobilized GroES was carried out using surface plasmon resonance.
      Excellent fits of the data were obtained using a double-exponential equation with
      a linear drift. Both the fast and slow observed dissociation rate constants are
      found to have a sigmoidal dependence on the concentration of ATP. The values of
      the Hill coefficients corresponding to the fast and slow observed rate constants
      of dissociation of wild-type GroEL and the Arg197-->Ala mutant are in good
      agreement with the respective values of the Hill coefficients previously
      determined for these proteins from plots of initial rates of ATP hydrolysis as a
      function of ATP concentration, in the presence of GroES. Our results are
      consistent with a kinetic mechanism for dissociation of the GroEL-GroES complex
      according to which GroES release takes place after an ATP-induced conformational
      change in the trans ring that is preceded by ATP hydrolysis and a subsequent
      conformational change in the cis ring. It is shown that the rate of complex
      dissociation increases with increasing positive cooperativity in ATP binding by
      the GroEL ring distal to GroES in the GroEL-GroES complex.

PMID- 11980499
TI  - Specific aspects of contemporary triathlon: implications for physiological
      analysis and performance.
AB  - Triathlon competitions are performed over markedly different distances and under
      a variety of technical constraints. In 'standard-distance' triathlons involving
      1.5km swim, 40km cycling and 10km running, a World Cup series as well as a World
      Championship race is available for 'elite' competitors. In contrast, 'age-group'
      triathletes may compete in 5-year age categories at a World Championship level,
      but not against the elite competitors. The difference between elite and age-group
      races is that during the cycle stage elite competitors may 'draft' or cycle in a
      sheltered position; age-group athletes complete the cycle stage as an individual
      time trial. Within triathlons there are a number of specific aspects that make
      the physiological demands different from the individual sports of swimming,
      cycling and running. The physiological demands of the cycle stage in elite races
      may also differ compared with the age-group format. This in turn may influence
      performance during the cycle leg and subsequent running stage. Wetsuit use and
      drafting during swimming (in both elite and age-group races) result in improved
      buoyancy and a reduction in frontal resistance, respectively. Both of these
      factors will result in improved performance and efficiency relative to normal
      pool-based swimming efforts. Overall cycling performance after swimming in a
      triathlon is not typically affected. However, it is possible that during the
      initial stages of the cycle leg the ability of an athlete to generate the high
      power outputs necessary for tactical position changes may be impeded. Drafting
      during cycling results in a reduction in frontal resistance and reduced energy
      cost at a given submaximal intensity. The reduced energy expenditure during the
      cycle stage results in an improvement in running, so an athlete may exercise at a
      higher percentage of maximal oxygen uptake. In elite triathlon races, the cycle
      courses offer specific physiological demands that may result in different fatigue
      responses when compared with standard time-trial courses. Furthermore, it is
      possible that different physical and physiological characteristics may make some
      athletes more suited to races where the cycle course is either flat or has
      undulating sections. An athlete's ability to perform running activity after
      cycling, during a triathlon, may be influenced by the pedalling frequency and
      also the physiological demands of the cycle stage. The technical features of
      elite and age-group triathlons together with the physiological demands of longer
      distance events should be considered in experimental design, training practice
      and also performance diagnosis of triathletes.

PMID- 11980500
TI  - The human spleen during physiological stress.
AB  - Many mammals have the ability to autotransfuse a large quantity of red blood
      cells from the spleen into the active circulation during times of stress. This
      enhancement of the oxygen transport system has benefited the athletic mammal,
      that is, the thoroughbred horse, fox and greyhound in an improved aerobic
      performance. The role of the spleen in sequestering 50% of the total red cell
      volume in seals and horses, during times of inactivity, dramatically reduces the
      viscosity of the blood and therefore the work of the heart. In comparison, the
      human spleen contains only a small percentage of red blood cells, and has been
      primarily thought of as a lymphoid organ. The aim of this review is to emphasise
      the similarities between the human spleen and that of several athletic mammalian
      species during acute physiological stress. In the athletic mammalian model the
      expulsion of blood from the spleen is facilitated via the sympathetic nervous
      system resulting in contraction of smooth muscle within the splenic capsule. In
      comparison, the lack of smooth muscle contained within the human splenic capsule
      has meant that active contraction of the spleen has historically been viewed as
      unlikely, although evidence of contractile proteins within the red pulp have
      suggested otherwise. Exercise results in haemoconcentration, which has been
      attributed solely to a reduction in plasma volume. Indirect calculation of plasma
      volume changes utilise haemoglobin and haematocrit and assume that the
      circulating red cell volume remains constant. However, several studies have
      suggested that the human spleen could account for 30% of the increase in
      haematocrit. This would result in a substantial overestimation of the reduction
      in plasma volume, indicating that the expulsion of red blood cells from the
      spleen must not be overlooked when utilising these equations.

PMID- 11980503
TI  - A piece of my mind. The music I want to hear.

PMID- 11980501
TI  - Nerve entrapments of the lower leg, ankle and foot in sport.
AB  - Exercise-related leg pain is a common and yet difficult management problem in
      sports medicine. There are many common causes of such symptoms including stress
      fractures and muscle compartment syndromes. There are also a number of less
      common but important conditions including popliteal artery entrapment and nerve
      entrapment syndromes. Even for an astute clinician, distinction between the
      different medical causes may be difficult given that many of their presenting
      features overlap. This review highlights the common clinical presentations and
      raises a regional approach to the diagnosis of the neurogenic symptoms. In part,
      this overlapping presentation of different pathological conditions may be due to
      a common aetiological basis of many of these conditions namely, fascial
      dysfunction. The same fascial restriction that predisposes to muscle compartment
      syndromes may also envelop the neurovascular structures within the leg resulting
      in either ischaemic or neurogenic symptoms. For many athletes with chronic
      exercise-related leg pain, combinations of such problems often coexist suggesting
      a more widespread fascial pathology. In our clinical experience, we often label
      such patients as 'fasciopaths'; however, the precise pathophysiological basis of
      this fascial problem remains to be elucidated. This review discusses the various
      nerve entrapment syndromes in the lower limb that may result in exercise-related
      leg pain in the sporting context. The anatomy, clinical presentation,
      investigation, medical management and surgical treatment are discussed at length
      for each of the syndromes. It is clear from clinical experience that the outcome
      of surgical management of such syndromes fares much better where a clear
      dermatomal pain distribution is present or where focal weakness and/or sensory
      symptoms appropriate for the nerve are present. In many situations, however,
      nonspecific leg pain or vague nonlocalising sensory symptoms are present and in
      such situations, alternative diagnoses must be considered and investigated
      appropriately. As mentioned above, many different pathologies may coexist in the
      lower limb and may be a source of confusion for the clinician or alternatively
      may be the reason for poor treatment outcomes.

PMID- 11980502
TI  - Posterior cruciate ligament injuries in the athlete: an anatomical, biomechanical
      and clinical review.
AB  - Recently, the posterior cruciate ligament (PCL) has become an increasingly
      popular subject of orthopaedic research and debate. In the past several years,
      anatomic and biomechanical studies have provided invaluable information
      concerning the structure and function of the PCL. However, many aspects of PCL
      injury are still not fully understood. Diagnosis of the injury is often missed
      because of subtlety of symptoms and clinical findings, and current management
      strategies of PCL injury have experienced relatively poor clinical outcomes.
      Controversy exists concerning the most appropriate treatment, especially in cases
      of isolated PCL injury. The purpose of this review is to present a complete
      overview of the current knowledge regarding the basic science and clinical
      aspects of PCL injuries, with a specific focus on the athletic population.

PMID- 11980505
TI  - The Surgeon General moves on: David Satcher plans to forward innovation.
      Interview by Rebecca Voelker.

PMID- 11980506
TI  - "Epidemic" of malignant melanoma: true increase or better detection?

PMID- 11980507
TI  - New source for information on rare diseases.

PMID- 11980508
TI  - From the Food and Drug Administration.

PMID- 11980512
TI  - Treatment of congestive heart failure.

PMID- 11980513
TI  - Treatment of congestive heart failure.

PMID- 11980514
TI  - Treatment of congestive heart failure.

PMID- 11980515
TI  - Treatment of congestive heart failure.

PMID- 11980516
TI  - Postmenopausal hormone replacement, body mass index, and quality of life.

PMID- 11980518
TI  - Varicella vaccine and shingles.

PMID- 11980520
TI  - Chocolate consumption and platelet function.

PMID- 11980521
TI  - Timing of new black box warnings and withdrawals for prescription medications.
AB  - CONTEXT: Recently approved drugs may be more likely to have unrecognized adverse
      drug reactions (ADRs) than established drugs, but no recent studies have examined
      how frequently postmarketing surveillance identifies important ADRs. OBJECTIVE:
      To determine the frequency and timing of discovery of new ADRs described in black
      box warnings or necessitating withdrawal of the drug from the market. DESIGN AND
      SETTING: Examination of the Physicians' Desk Reference for all new chemical
      entities approved by the US Food and Drug Administration between 1975 and 1999,
      and all drugs withdrawn from the market between 1975 and 2000 (with or without a
      prior black box warning). MAIN OUTCOME MEASURES: Frequency of and time to a new
      black box warning or drug withdrawal. RESULTS: A total of 548 new chemical
      entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning
      or were withdrawn. Forty-five drugs (8.2%) acquired 1 or more black box warnings
      and 16 (2.9%) were withdrawn from the market. In Kaplan-Meier analyses, the
      estimated probability of acquiring a new black box warning or being withdrawn
      from the market over 25 years was 20%. Eighty-one major changes to drug labeling
      in the Physicians' Desk Reference occurred including the addition of 1 or more
      black box warnings per drug, or drug withdrawal. In Kaplan-Meier analyses, half
      of these changes occurred within 7 years of drug introduction; half of the
      withdrawals occurred within 2 years. CONCLUSIONS: Serious ADRs commonly emerge
      after Food and Drug Administration approval. The safety of new agents cannot be
      known with certainty until a drug has been on the market for many years.

PMID- 11980522
TI  - Preoperative beta-blocker use and mortality and morbidity following CABG surgery
      in North America.
AB  - CONTEXT: beta-Blockade therapy has recently been shown to convey a survival
      benefit in preoperative noncardiac vascular surgical settings. The effect of
      preoperative beta-blocker therapy on coronary artery bypass graft surgery (CABG)
      outcomes has not been assessed. OBJECTIVES: To examine patterns of use of
      preoperative beta-blockers in patients undergoing isolated CABG and to determine
      whether use of beta-blockers is associated with lower operative mortality and
      morbidity. DESIGN, SETTING, AND PATIENTS: Observational study using the Society
      of Thoracic Surgeons National Adult Cardiac Surgery Database (NCD) to assess beta
      blocker use and outcomes among 629 877 patients undergoing isolated CABG between
      1996 and 1999 at 497 US and Canadian sites. MAIN OUTCOME MEASURE: Influence of
      beta-blockers on operative mortality, examined using both direct risk adjustment
      and a matched-pairs analysis based on propensity for preoperative beta-blocker
      therapy. RESULTS: From 1996 to 1999, overall use of preoperative beta-blockers
      increased from 50% to 60% in the NCD (P<.001 for time trend). Major predictors of
      use included recent myocardial infarction; hypertension; worse angina; younger
      age; better left ventricular systolic function; and absence of congestive heart
      failure, chronic lung disease, and diabetes. Patients who received beta-blockers
      had lower mortality than those who did not (unadjusted 30-day mortality, 2.8% vs
      3.4%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.78-0.82).
      Preoperative beta-blocker use remained associated with slightly lower mortality
      after adjusting for patient risk and center effects using both risk adjustment
      (OR, 0.94; 95% CI, 0.91-0.97) and treatment propensity matching (OR, 0.97; 95%
      CI, 0.93-1.00). Procedural complications also tended to be lower among treated
      patients. This treatment advantage was seen among the majority of patient
      subgroups, including women; elderly persons; and those with chronic lung disease,
      diabetes, or moderately depressed ventricular function. Among patients with a
      left ventricular ejection fraction of less than 30%, however, preoperative beta
      blocker therapy was associated with a trend toward a higher mortality rate (OR,
      1.13; 95% CI, 0.96-1.33; P =.23). CONCLUSIONS: In this large North American
      observational analysis, preoperative beta-blocker therapy was associated with a
      small but consistent survival benefit for patients undergoing CABG, except among
      patients with a left ventricular ejection fraction of less than 30%. This
      analysis further suggests that preoperative beta-blocker therapy may be a useful
      process measure for CABG quality improvement assessment.

PMID- 11980523
TI  - Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic
      factor.
AB  - CONTEXT: The pathogenesis of high-altitude pulmonary edema (HAPE) is considered
      an altered permeability of the alveolar-capillary barrier secondary to intense
      pulmonary vasoconstriction and high capillary pressure, but previous
      bronchoalveolar lavage (BAL) findings in well-established HAPE are also
      consistent with inflammatory etiologic characteristics. OBJECTIVES: To determine
      whether inflammation is a primary event in HAPE and to define the temporal
      sequence of events in HAPE. DESIGN, SETTING, AND PARTICIPANTS: Case study from
      July through August 1999 of 10 subjects with susceptibility to HAPE and 6
      subjects resistant to HAPE, all of whom are nonprofessional alpinists with
      previous mountaineering experience above 3000 m. MAIN OUTCOME MEASURES: Pulmonary
      artery pressure measurements and BAL findings at low altitude (490 m) and shortly
      before or at the onset of HAPE at an altitude of 4559 m. RESULTS: Subjects who
      were HAPE susceptible had higher mean (SD) pulmonary artery systolic blood
      pressures at 4559 m compared with HAPE-resistant subjects (66 vs 37 mm Hg; P
      =.004). Despite development of HAPE in the majority of HAPE-susceptible subjects,
      there were no differences in BAL fluid total leukocyte counts between resistant
      and susceptible subjects or between counts taken at low and high altitudes.
      Subjects who developed HAPE had BAL fluid with high concentrations of plasma
      derived proteins and erythrocytes, but there was no increase in plasma
      concentrations of surfactant protein A and Clara cell protein. The chest
      radiograph score was 12.7 for the 3 HAPE-susceptible subjects who developed HAPE
      before BAL was performed; they were lavaged within 3 to 5 hours. The remainder of
      the HAPE-susceptible group was lavaged before edema was apparent on radiographs.
      However, 6 subjects from the HAPE-susceptible group who developed HAPE on the
      following day had a score on bronchoscopy of 1.5, which increased to 4.6,
      reflective of mild pulmonary edema. In HAPE cases, there were no elevations in a
      number of proinflammatory cytokines and eicosanoid and nitric oxide metabolites.
      CONCLUSIONS: Early HAPE is characterized by high pulmonary artery pressures that
      lead to a protein-rich and mildly hemorrhagic edema, with normal levels of
      leukocytes, cytokines, and eicosanoids. HAPE is a form of hydrostatic pulmonary
      edema with altered alveolar-capillary permeability.

PMID- 11980524
TI  - Anthrax as a biological weapon, 2002: updated recommendations for management.
AB  - OBJECTIVE: To review and update consensus-based recommendations for medical and
      public health professionals following a Bacillus anthracis attack against a
      civilian population. PARTICIPANTS: The working group included 23 experts from
      academic medical centers, research organizations, and governmental, military,
      public health, and emergency management institutions and agencies. EVIDENCE:
      MEDLINE databases were searched from January 1966 to January 2002, using the
      Medical Subject Headings anthrax, Bacillus anthracis, biological weapon,
      biological terrorism, biological warfare, and biowarfare. Reference review
      identified work published before 1966. Participants identified unpublished
      sources. CONSENSUS PROCESS: The first draft synthesized the gathered information.
      Written comments were incorporated into subsequent drafts. The final statement
      incorporated all relevant evidence from the search along with consensus
      recommendations. CONCLUSIONS: Specific recommendations include diagnosis of
      anthrax infection, indications for vaccination, therapy, postexposure
      prophylaxis, decontamination of the environment, and suggested research. This
      revised consensus statement presents new information based on the analysis of the
      anthrax attacks of 2001, including developments in the investigation of the
      anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new
      diagnostic clues that may help future recognition of this disease; current
      anthrax vaccine information; updated antibiotic therapeutic considerations; and
      judgments about environmental surveillance and decontamination.

PMID- 11980525
TI  - Dignity-conserving care--a new model for palliative care: helping the patient
      feel valued.
AB  - The basic tenets of palliative care may be summarized as the goal of helping
      patients to die with dignity. The term "dignity" provides an overarching
      framework that may guide the physician, patient, and family in defining the
      objectives and therapeutic considerations fundamental to end-of-life care.
      Dignity-conserving care is care that may conserve or bolster the dignity of dying
      patients. Using segments of interviews with a patient with advanced lung cancer,
      his wife, and his palliative care physician, this article illustrates and
      explores various aspects of dignity-conserving care and the model on which it is
      based. Dignity-conserving care offers an approach that clinicians can use to
      explicitly target the maintenance of dignity as a therapeutic objective and as a
      principle of bedside care for patients nearing death.

PMID- 11980526
TI  - Management of dyspnea in patients with far-advanced lung disease.

PMID- 11980527
TI  - Does this patient have an acute thoracic aortic dissection?
AB  - CONTEXT: The diagnosis of acute thoracic aortic dissection is difficult to make
      and often missed. OBJECTIVE: To review the accuracy of clinical history taking,
      physical examination, and plain chest radiograph in the diagnosis of acute
      thoracic aortic dissection. DATA SOURCES: A comprehensive review of the English
      language literature was conducted using MEDLINE for the years 1966 through 2000.
      Additional sources were identified from the references of retrieved articles.
      STUDY SELECTION: The search revealed 274 potential sources, which were reviewed
      for pertinence and quality. Articles included were original investigations
      describing the clinical findings for 18 or more consecutive patients with
      confirmed thoracic aortic dissection. Twenty-one studies were identified that met
      selection criteria. DATA EXTRACTION: Critical appraisal and data extraction were
      performed by the author. DATA SYNTHESIS: Most patients with thoracic aortic
      dissection have severe pain (pooled sensitivity, 90%) of sudden onset
      (sensitivity, 84%). The absence of sudden pain onset lowers the likelihood of
      dissection (negative likelihood ratio [LR], 0.3; 95% confidence interval [CI],
      0.2-0.5). On examination, 49% of patients have an elevated blood pressure, 28%
      have a diastolic murmur, 31% have pulse deficits or blood pressure differentials,
      and 17% have focal neurological deficits. Presence of a diastolic murmur does
      little to change the pretest probability of dissection (positive LR, 1.4; 95% CI,
      1.0-2.0), whereas pulse or blood pressure differentials and neurological deficits
      increase the likelihood of disease (positive LRs, 5.7 and 6.6-33.0,
      respectively). The plain chest radiograph results are usually abnormal
      (sensitivity, 90%); hence, the presence of a normal aorta and mediastinum
      decreases the probability of dissection (negative LR, 0.3; 95% CI, 0.2-0.4).
      Combinations of findings increase the likelihood of disease. CONCLUSIONS: The
      presence of pulse deficits or focal neurological deficits increases the
      likelihood of an acute thoracic aortic dissection in the appropriate clinical
      setting. Conversely, a completely normal chest radiograph result or the absence
      of pain of sudden onset lowers the likelihood. Overall, however, the clinical
      examination is insufficiently sensitive to rule out aortic dissection given the
      high morbidity of missed diagnosis.

PMID- 11980528
TI  - Safety of newly approved drugs: implications for prescribing.

PMID- 11980531
TI  - MSJAMA: The public health implications of global warming.

PMID- 11980529
TI  - High-altitude pulmonary edema.

PMID- 11980532
TI  - MSJAMA: Global climate change and health: challenges for future practitioners.

PMID- 11980533
TI  - MSJAMA: Global climate change and air pollution: common origins with common
      solutions.

PMID- 11980534
TI  - MSJAMA: Climate change and the monitoring of vector-borne disease.

PMID- 11980535
TI  - MSJAMA: Climate change and human health: the critical policy agenda.

PMID- 11980543
TI  - First, observe the patient.

PMID- 11980544
TI  - Publication bias: the problem and some suggestions.

PMID- 11980545
TI  - Adolescent vegetarians: how well do their dietary patterns meet the healthy
      people 2010 objectives?

PMID- 11980546
TI  - The role of early, multilevel youth development programs in preventing health
      risk behavior in adolescents and young adults.

PMID- 11980547
TI  - Adolescent vegetarians: how well do their dietary patterns meet the healthy
      people 2010 objectives?
AB  - OBJECTIVES: To examine whether adolescent vegetarians were more likely than
      nonvegetarian peers to meet the dietary recommendations of the Healthy People
      2010 objectives and to examine differences in other nutrients between these 2
      groups. DESIGN: A total of 4746 adolescents from 31 middle and high schools in
      the Twin Cities area of Minnesota. Data were collected via self-report surveys,
      with a student response rate of 81.5%. SETTING: Urban secondary schools.
      PARTICIPANTS: Participants were equally divided by sex. The mean age was 14.9
      years; 34.3% were in junior high school and 65.7% in high school. The
      racial/ethnic distribution was 48.5% white, 19.0% African American, 19.2% Asian
      American, 5.8% Hispanic, 3.5% American Indian, and 3.9% mixed or other. MAIN
      OUTCOME MEASURES: Questions on vegetarian status and whether particular foods
      (eggs, dairy foods, chicken, fish) were excluded. Dietary intake was assessed
      using the Youth and Adolescent Food Frequency Questionnaire. RESULTS: Vegetarian
      adolescents were significantly more likely than nonvegetarian adolescents to meet
      the Healthy People 2010 objectives. This was particularly noteworthy for total
      fat (70% vs 48%), saturated fat (65% vs 39%), daily servings of vegetables (26%
      vs 14%), and 5 or more servings of fruits and vegetables (39% vs 28%).
      Vegetarians were also less likely to eat fast food or drink regular soda and
      fruit drinks. Vegetarians consumed less vitamin B(12), more diet soda, more
      caffeine, and more iron. CONCLUSION: Adolescent vegetarians have a dietary
      pattern that is more likely than nonvegetarians to meet the Healthy People 2010
      objectives.

PMID- 11980548
TI  - Effects of the Seattle social development project on sexual behavior, pregnancy,
      birth, and sexually transmitted disease outcomes by age 21 years.
AB  - OBJECTIVE: To examine the long-term effects of the full Seattle Social
      Development Project intervention on sexual behavior and associated outcomes
      assessed at age 21 years. DESIGN: Nonrandomized controlled trial with long-term
      follow-up. SETTING: Public elementary schools serving children from high-crime
      areas in Seattle, Wash. PARTICIPANTS: Ninety-three percent of the fifth-grade
      students enrolled in either the full-intervention or control group were
      successfully interviewed at age 21 years (n = 144 [full intervention] and n = 205
      [control]). INTERVENTIONS: In-service teacher training, parenting classes, and
      social competence training for children. MAIN OUTCOME MEASURES: Self-report
      measures of all outcomes. RESULTS: The full-intervention group reported
      significantly fewer sexual partners and experienced a marginally reduced risk for
      initiating intercourse by age 21 years as compared with the control group. Among
      females, treatment group status was associated with a significantly reduced
      likelihood of both becoming pregnant and experiencing a birth by age 21 years.
      Among single individuals, a significantly increased probability of condom use
      during last intercourse was predicted by full-intervention group membership; a
      significant ethnic group x intervention group interaction indicated that after
      controlling for socioeconomic status, single African Americans were especially
      responsive to the intervention in terms of this outcome. Finally, a significant
      treatment x ethnic group interaction indicated that among African Americans,
      being in the full-intervention group predicted a reduced probability of
      contracting a sexually transmitted disease by age 21 years. CONCLUSION: A theory
      based social development program that promotes academic success, social
      competence, and bonding to school during the elementary grades can prevent risky
      sexual practices and adverse health consequences in early adulthood.

PMID- 11980549
TI  - Socioeconomic status, depressive symptoms, and adolescent substance use.
AB  - OBJECTIVE: To determine the relationships among socioeconomic status (SES),
      depression, and substance use among teenagers. We hypothesized that, among
      teenagers, substance use was associated with SES in a graded fashion and that
      depression is a mechanism through which SES affects substance use behaviors.
      DESIGN: Linear regression analyses of cross-sectional data from Wave I of the
      National Longitudinal Study of Adolescent Health (1995). PARTICIPANTS: Fifteen
      thousand one hundred twelve adolescents whose parents answered questions
      assessing household income and parental education. MAIN OUTCOME MEASURES: Use of
      cigarettes, alcohol, marijuana, and cocaine. RESULTS: For all 4 substances,
      frequency of use varied by SES. In the total population, inverse SES gradients
      were present for cigarette use (education, mean change= -0.052; 95% confidence
      interval [CI], -0.081 to -0.023; income, mean change= -0.038; 95% CI, -0.069 to 
      0.007) and alcohol use (income, mean change= 0.044; 95% CI, 0.016-0.071). The
      relationship between marijuana use and education was also significant but inverse
      U-shaped, not linear. This relationship was only present among nonwhite
      teenagers. Race/ethnicity also moderated the relationships between SES and
      cigarette use and SES and cocaine use. For cigarette use, stratification by
      race/ethnicity revealed an inverse graded relationship among white non-Hispanic
      teenagers and a direct, graded relationship among nonwhite teenagers (ie, mean
      change for education among white non-Hispanic teenagers, -0.012; 95% CI, -0.016
      to -0.075; mean change for education among nonwhite teenagers, 0.040; 95% CI,
      0.014-0.072). For cocaine use, a weak, inverse linear relationship existed only
      between education and cocaine use among white non-Hispanic teenagers (mean change
      for education, -0.013; 95% CI, -0.026 to -0.0004). The relationship between the
      SES indicator and substance use weakened when depressive symptoms were entered
      into the model for the SES-cigarette use relationship (23% decrease in mean
      change associated with a 1-unit change in both education and income) and for the
      association between education and cocaine use among white non-Hispanic teenagers
      (31% decrease). CONCLUSIONS: Socioeconomic status is associated with substance
      use among teenagers but the nature of the relationship is not consistent across
      SES indicators or across race/ethnicity groups. Depressive symptoms are a
      mechanism through which SES affects cigarette and cocaine use behaviors among
      teenagers. However, these data indicate that interventions targeted toward
      decreasing depressive symptoms will not have a strong impact on the effects of
      SES on teenage substance use.

PMID- 11980550
TI  - Child sex differences in primary care clinicians' mental health care of children
      and adolescents.
AB  - BACKGROUND: Sex differences in the medical and mental health care of adults are
      well established. OBJECTIVE: To study the effect of child patient's sex on
      whether primary care clinicians (PCCs), including pediatricians, family
      physicians, and nurse practitioners, found or treated mental health problems in
      primary care settings. DESIGN: The data were collected by clinicians and parents
      from 21 065 individual child visits (50.3% girls) in 204 primary care practices.
      METHODS: Each PCC enrolled a consecutive sample of approximately 55 children and
      adolescents aged 4 to 15 years. Parents filled out questionnaires, including the
      Pediatric Symptom Checklist, before seeing the clinician. Clinicians completed a
      survey after the visit about the psychosocial problems and recommended
      treatments, but they did not see the results of the Pediatric Symptom Checklist
      or any other data collected from the parents. RESULTS: Boys were more likely to
      be seen for a mental health-related visit and by a clinician who identified them
      as "my patient." Boys with parent-reported symptom profiles that were similar to
      those of girls were more likely to be identified as having attention
      deficit/hyperactivity problems or behavior or conduct problems and less likely to
      be identified as having internalizing problems. Adjusting for parent-reported
      symptoms, PCCs were more likely to prescribe medications for boys. Child sex
      differences in referrals to mental health specialists and the provision of
      counseling to families were not statistically significant. CONCLUSION: There are
      substantial sex differences in the mental health care of children in the primary
      care system.

PMID- 11980551
TI  - Cramped synchronized general movements in preterm infants as an early marker for
      cerebral palsy.
AB  - OBJECTIVE: To ascertain whether specific abnormalities (ie, cramped synchronized
      general movements [GMs]) can predict cerebral palsy and the severity of later
      motor impairment in preterm infants affected by brain lesions. DESIGN:
      Traditional neurological examination was performed, and GMs were serially
      videotaped and blindly observed for 84 preterm infants with ultrasound
      abnormalities from birth until 56 to 60 weeks' postmenstrual age. The
      developmental course of GM abnormalities was compared with brain ultrasound
      findings alone and with findings from neurological examination, in relation to
      the patient's outcome at age 2 to 3 years. RESULTS: Infants with consistent or
      predominant (33 cases) cramped synchronized GMs developed cerebral palsy. The
      earlier cramped synchronized GMs were observed, the worse was the neurological
      outcome. Transient cramped synchronized character GMs (8 cases) were followed by
      mild cerebral palsy (fidgety movements were absent) or normal development
      (fidgety movements were present). Consistently normal GMs (13 cases) and poor
      repertoire GMs (30 cases) either lead to normal outcomes (84%) or cerebral palsy
      with mild motor impairment (16%). Observation of GMs was 100% sensitive, and the
      specificity of the cramped synchronized GMs was 92.5% to 100% throughout the age
      range, which is much higher than the specificity of neurological examination.
      CONCLUSIONS: Consistent and predominant cramped synchronized GMs specifically
      predict cerebral palsy. The earlier this characteristic appears, the worse is the
      later impairment.

PMID- 11980552
TI  - Low risk of bacteremia in children with febrile seizures.
AB  - OBJECTIVE: To evaluate the risk of bacteremia in children with febrile seizures
      treated as outpatients. METHODS: A retrospective cohort study was performed
      involving 379 children aged 2 to 24 months presenting to an urban tertiary care
      children's hospital emergency department with a febrile seizure between February
      1, 1993, and May 31, 1996. RESULTS: The mean patient age was 15.9 months, and 217
      (57%) were male. In 40 patients (10.6%), the use of oral antibiotics before
      initial emergency department evaluation was reported. Bacteremia occurred in 8
      (2.1%) of 379 children studied. None of the children with bacteremia had received
      previous antibiotics. The causative organisms were Streptococcus pneumoniae in 7
      cases and group A Streptococcus in 1 case. There were 5 contaminated cultures
      (1.3%). Although 2 of the 8 children with bacteremia ultimately required
      admission, there were no serious adverse outcomes. Six of 7 episodes of S
      pneumoniae bacteremia were caused by serotypes included in the pneumococcal
      conjugate vaccine, which was not available at the time of this study.
      CONCLUSIONS: Children 2 to 24 months of age with febrile seizures are at similar
      risk for occult bacteremia as those with fever alone. Widespread use of the
      pneumococcal conjugate vaccine may further decrease the incidence of bacteremia
      in this population.

PMID- 11980553
TI  - Abstracts of randomized controlled trials presented at the society for pediatric
      research meeting: an example of publication bias.
AB  - BACKGROUND: Publication bias toward studies that favor new therapies has been
      known to occur for the past 40 years, yet its implications are not well studied
      in child health. The increased interest in meta-analyses has highlighted the need
      to identify the totality of evidence when addressing treatment questions.
      OBJECTIVES: To measure the percentage of randomized controlled trials (RCTs)
      presented at a major pediatric scientific meeting that were subsequently
      published as full-length articles, to investigate factors associated with
      publication, and to describe the variables that change from abstract to
      manuscript form. DESIGN: The scientific proceedings from the Society for
      Pediatric Research were hand searched for RCTs (1992-1995). Subsequent
      publication was ascertained through a search of various electronic databases.
      Quality of abstracts and manuscripts was measured, and data were extracted using
      a structured form. RESULTS: A total of 264 (59.1%) of 447 abstracts were
      subsequently published. Almost 64% of RCTs that were subsequently published
      favored new therapy compared with 43.5% of studies that were never published
      (P<.001). Mean effect size for published vs unpublished RCTs was 0.74 vs 0.05
      (P<.001). Median sample size was larger in published (n = 45) vs unpublished (n =
      34) RCTs (P =.02). Quality was significantly lower for abstracts vs published
      RCTs (P<.001). For 5% of abstracts that were subsequently published, the
      conclusion regarding treatment efficacy changed. CONCLUSIONS: Publication bias is
      a serious threat to assessing the effectiveness of interventions in child health,
      as little more than half of RCTs presented at a major scientific meeting are
      subsequently published. There is a need to institute an international registry of
      RCTs in children so that the totality of evidence can be accessed when assessing
      treatment effectiveness.

PMID- 11980554
TI  - An anomaly within the Latino epidemiological paradox: the Latino adolescent male
      mortality peak.
AB  - OBJECTIVE: To describe the anomaly of the Latino adolescent male mortality peak
      in relation to the overall Latino epidemiological paradox and in relation to the
      need for new conceptual models describing the health of a culturally diverse
      population. DESIGN: Population-based study using California's 1989 to 1997
      summary death files for death-related information and the State of California
      Department of Finance population estimates for population denominators for
      corresponding years. PARTICIPANTS: California's general population for 1989 to
      1997, including California's 15- to 19-year-old and 20- to 24-year-old
      populations. In 1997, those 2 age groups numbered 4.3 million. MAIN OUTCOME
      MEASURES: Mortality rates for Latinos and African Americans compared with non
      Hispanic whites expressed as relative risk (RR). RESULTS: Overall, the Latino RR
      of mortality follows the Latino epidemiological paradox in that it is lower (RR,
      <1.00) than that of non-Hispanic whites for most age groups and both sexes. The
      anomaly within this paradox is seen in Latino males aged 15 to 19 years (RR,
      1.77; 95% confidence interval, 1.55-2.02) and 20 to 24 years (RR, 1.79; 95%
      confidence interval, 1.58-2.02). CONCLUSIONS: This period of elevated mortality
      risk is labeled the Latino adolescent male mortality peak, and it is an anomaly
      within the overall Latino epidemiological paradox.

PMID- 11980555
TI  - Starting dose of levothyroxine for the treatment of congenital hypothyroidism: a
      systematic review.
AB  - OBJECTIVE: To determine the effect of levothyroxine sodium starting dose on
      cognitive development, growth, or behavior in children with congenital
      hypothyroidism identified by neonatal screening. DESIGN: Systematic review of
      cohort studies. Two analyses were performed: a between-study comparison of mean
      starting dose with mean developmental score and an analysis of the within-study
      effects of starting dose on cognitive development, growth, or behavior. RESULTS:
      The between-study comparison (14 cohort studies based on 1321 patients) found
      that the standardized mean IQ or developmental quotient scores ranged from 90 to
      115 but were not associated with the mean starting dose of levothyroxine (P
      =.48). The within-study comparison of 4 cohort studies (based on 558 patients)
      that reported the effect of the starting dose of levothyroxine on cognitive
      development found no consistent effects. There was weak evidence for an effect of
      starting dose on growth (1 study) and on behavior problems (1 study).
      CONCLUSIONS: The evidence for an effect of starting dose of levothyroxine on
      cognitive development, growth, or behavior is too weak to justify recommendations
      in favor of high- or standard-dose regimens. More reliable information, based on
      a randomized controlled trial of starting dose or a meta-analysis of the
      individual patient data currently available, is required to inform treatment
      policies.

PMID- 11980556
TI  - An evaluation of hospitalizations for Kawasaki syndrome in Georgia.
AB  - OBJECTIVE: To evaluate and describe the epidemiologic characteristics of Kawasaki
      syndrome (KS) hospitalizations in Georgia. DESIGN: We reviewed hospital discharge
      data and corresponding medical records for Georgian patients discharged with a KS
      diagnosis during 1997 and 1998. RESULTS: During the study period, 233 KS hospital
      discharges were recorded in Georgia; 177 (76%) were for children younger than 5
      years. Twenty-one (9%) of 233 of the hospital discharges represented multiple
      hospitalizations. Medical records for 211 KS discharges (91%), representing 197
      patients (93%), were reviewed. For those 189 patients whose medical records were
      reviewed and had sufficient information, 139 (74%) either had a documented
      illness that met the Centers for Disease Control and Prevention (CDC) definition
      for KS (n = 135) or had coronary artery abnormalities without meeting the CDC
      definition for KS (atypical KS; n = 4). Eight patients had only a history of KS.
      Excluding multiple hospitalizations and patients with only a history of KS, 158
      hospitalizations were for patients younger than 5 years (14.0 per 100 000
      children); 110 of these patients met the KS or atypical KS definition (9.8 per
      100 000 children). CONCLUSIONS: Hospital discharge data are useful for KS
      surveillance. However, analysis of hospital discharge data may slightly
      overestimate the KS hospitalization rates because some discharges may represent
      multiple hospitalizations or hospitalizations of patients with only a history of
      KS. The incidence and epidemiology of KS in Georgia are consistent with findings
      from other continental US studies. Physicians should exercise their best clinical
      judgment in identifying and treating patients with KS who may not meet standard
      case definitions.

PMID- 11980557
TI  - Growth in human immunodeficiency virus-infected children receiving ritonavir
      containing antiretroviral therapy.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected children often suffer
      from impaired growth. Highly active antiretroviral therapy (HAART) successfully
      reduces HIV 1 (HIV-1) RNA to 400 copies/mL or less in many children. OBJECTIVES:
      To determine if age- and sex-adjusted growth z scores correlate with HIV-1 RNA
      level and if control of viral load for 48 and 96 weeks results in improved growth
      in children receiving highly active antiretroviral therapy. DESIGN: Secondary
      analysis of the cohort of children receiving ritonavir nested in a randomized,
      open-label, clinical trial. SUBJECTS AND METHODS: The Pediatric AIDS Clinical
      Trials Group Protocol 338 enrolled clinically stable, antiretroviral therapy
      experienced, HIV-infected subjects aged 2 through 17 years. Using data from
      subjects randomized to ritonavir-containing regimens (n = 197), the association
      of growth z scores and HIV-1 RNA levels were examined. MAIN OUTCOME MEASURES: Age
      and sex-adjusted weight and height z scores. RESULTS: Enrollment weights were
      comparable with age- and sex-adjusted norms, but subjects receiving ritonavir
      containing antiretroviral therapy were significantly shorter (mean z score, -0.57
      [29th percentile]; 95% confidence interval, -0.73 to -0.40). Higher HIV-1 RNA
      levels correlated with lower growth z scores (P<.01). Subjects achieving and
      maintaining HIV-1 RNA of 400 copies/mL or less through 48 and 96 weeks
      experienced worse growth than subjects with a less controlled viral load.
      CONCLUSIONS: In this pediatric cohort, a significant decline in height and weight
      z scores was found despite control of viral replication. Further studies of
      growth are necessary to assess if nutritional and hormonal adjuvants to highly
      active antiretroviral therapy should be considered to improve growth in HIV
      infected children.

PMID- 11980558
TI  - Health care use and costs for children with attention-deficit/hyperactivity
      disorder: national estimates from the medical expenditure panel survey.
AB  - CONTEXT: Although attention-deficit/hyperactivity disorder (ADHD) is a highly
      prevalent chronic condition of childhood, little is known about patterns of
      health care use and associated expenditures. OBJECTIVE: To compare health care
      use and costs among children with ADHD, children with asthma, and the general
      pediatric population. DESIGN AND SETTING: The 1996 Medical Expenditure Panel
      Survey, a nationally representative household survey. PARTICIPANTS: All 5439
      children aged 5 to 20 years from the 1996 Medical Expenditure Panel Survey were
      included in this analysis. Children who had ADHD, asthma, or neither (general
      population) were identified from International Classification of Diseases, Ninth
      Revision, Clinical Modification codes and prescription records. MAIN OUTCOME
      MEASURES: Mean health care use (outpatient visits, emergency department visits,
      hospital stays, home health visit days, and prescriptions) and associated
      expenditures. RESULTS: We identified 165 children with ADHD, 322 with asthma, and
      4952 with neither diagnosis. Children with ADHD had significantly higher mean
      total health care costs ($1151) compared with children with asthma ($1091; P<.05)
      and the general population ($712; P<.001). After adjusting for age, sex, race,
      household income, access to care, parent education, and marital status, excess
      total costs were $479 for children with ADHD (P<.001) and $437 for children with
      asthma (P<.01). CONCLUSIONS: Overall costs of care for children with ADHD are
      comparable to costs for children with asthma and significantly greater than for
      the general pediatric population. Specific types of health care use and the
      sources of expenditures differ between children with ADHD and children with
      asthma. Because much ADHD-related care occurs within school and mental health
      settings, these figures likely underestimate the true costs of caring for
      children with this condition.

PMID- 11980559
TI  - Risk of serious bacterial infection in children with fever without a source in
      the post-Haemophilus influenzae era when antibiotics are reserved for culture
      proven bacteremia.
AB  - OBJECTIVE: To determine the rate of serious bacterial infection in children aged
      2 to 36 months with fever without a source in the post-Haemophilus influenzae
      era, when antibiotic therapy is reserved until blood culture results turn
      positive. DESIGN AND SETTING: Retrospective review of emergency department,
      urgent care center, and hospital medical records from an urban children's
      hospital. PARTICIPANTS: Eligible participants were identified from hospital
      medical record and microbiology laboratory databases. Immunocompetent individuals
      aged 2 to 36 months with fever without a source were eligible for enrollment.
      Exclusion criteria were temperature less than 39.0 degrees C, identifiable focus
      of infection, current or recent antibiotic use, and hospital admission.
      INTERVENTIONS AND OUTCOME MEASURES: Enrolled participants were assigned to group
      1 (blood culture obtained) or group 2 (no blood culture) and did not receive
      empiric antibiotic treatment in the emergency department, in the urgent care
      center, or for home use. Demographic and outcome data were collected on all
      enrolled patients. RESULTS: During the study, 9241 febrile children were
      identified; 2641 (29%) met the enrollment criteria. Blood cultures (group 1) were
      performed on 1202 patients (46%), and 37 (3%) had culture-proven occult
      bacteremia (95% confidence interval, 2.2%-4.2%). Streptococcus pneumoniae was the
      most prevalent organism (84%). The mean +/- SD time for reporting a positive
      blood culture finding was 17.5 +/- 8.5 hours. Two patients (0.08%; 95% confidence
      interval, 0.009%-0.27%) developed serious bacterial infection, and both recovered
      completely. CONCLUSION: Reserving antibiotic therapy for culture-proven occult
      bacteremia was not associated with increased risk of developing serious bacterial
      infection compared with previously published data.

PMID- 11980560
TI  - The pediatric forum: effective elements of literacy intervention: book, talk, or
      both?

PMID- 11980561
TI  - The prevention of toddler iron deficiency.

PMID- 11980562
TI  - Lysosome-associated protein transmembrane 4 alpha (LAPTM4 alpha) requires two
      tandemly arranged tyrosine-based signals for sorting to lysosomes.
AB  - Lysosome-associated protein transmembrane 4 alpha (LAPTM4 alpha) and homologues
      comprise a family of conserved proteins, which are found in mammals, insects and
      nematodes. LAPTM4 alpha functions to regulate the intracellular
      compartmentalization of amphipathic solutes and possibly the sensitivity of cells
      toward anthracyclines, antibiotics, ionophores, nucleobases and organic cations.
      This is similar to the multidrug-resistance phenotype exhibited by cells
      synthesizing high levels of P-glycoprotein. Accordingly, it is possible that
      LAPTM4 alpha may be a suitable target for development of novel chemotherapeutic
      agents. LAPTM4 alpha contains four putative membrane-spanning domains and a 55
      amino acid C-terminal region that faces the cytoplasm. Localization of LAPTM4
      alpha to endosomes and lysosomes appears to be tightly controlled as transient
      high-level expression of LAPTM4 alpha in cultured cells resulted in no detectable
      protein on the cell surface. Mutagenic analysis of the C-terminus of LAPTM4 alpha
      indicated that two tandomly arranged tyrosine-containing motifs in the
      cytoplasmic domain are required for efficient localization of LAPTM4 alpha to
      vesicles containing the lysosomal marker lysosomal glycoprotein 120. Although a
      number of membrane proteins that localize to endosomes/lysosomes contain more
      than one independently functioning sorting signal, to our knowledge, LAPTM4 alpha
      is the first example of a membrane protein that requires two tandemly arranged
      tyrosine-based sorting signals for efficient localization in these compartments.

PMID- 11980563
TI  - OTEX, an androgen-regulated human member of the paired-like class of homeobox
      genes.
AB  - paired genes emerged early in evolution and code for homeobox transcription
      factors, having fundamental roles in various biological processes. We identified
      a novel human member of the paired-like class, which we named OTEX. A
      phylogenetic analysis revealed that OTEX belonged to the recently defined PEPP
      subfamily of paired-like homeobox genes. It was organized into three introns and,
      like the other PEPP genes, it was mapped to chromosome X. Its transcripts were
      detected mainly in the ovary, testis and epididymis, but also in the prostate and
      mammary gland. In the PC-3/ARwt prostate cell line, OTEX expression was
      stimulated dramatically following androgen treatment. Immunofluorescence studies
      revealed an exclusively nuclear localization of the OTEX protein. Mutation of the
      RARCRRHQRE amino acid sequence present at the C-terminus of the OTEX homeodomain
      resulted in a mainly cytoplasmic localization, indicating that this motif
      harboured the nuclear localization signal. No inherent transactivation function
      was seen for OTEX using the one-hybrid assay, and no homodimer formation was
      observed in the two-hybrid assay, suggesting that additional partners were needed
      for this activity. Taken together, the data show that OTEX represents a novel,
      androgen-regulated, paired-like homeobox protein, with possibly an important role
      in human reproduction.

PMID- 11980564
TI  - The immunopathogenesis of paraneoplastic neurological syndromes.
AB  - Paraneoplastic neurological syndromes are rare non-metastatic complications of
      cancer that have an immune-mediated aetiology. The central and peripheral nervous
      systems are considered to be immune-privileged sites, since the presence of the
      'blood-brain/nerve barrier' means that antigens sequestered within the nervous
      system do not normally induce an immune response. Aberrant expression of a
      neuronal antigen by a tumour arising outside this barrier can lead to the
      breakdown of immune tolerance to the nervous system. However, in many cases the
      immune mechanisms that result in neurological dysfunction remain poorly defined.
      Furthermore, aberrant expression of neuronal antigens can be detected in many
      tumours that are not complicated by non-metastatic neurological syndromes. This
      review article examines current concepts in the immunopathogenesis of
      paraneoplastic neurological syndromes.

PMID- 11980565
TI  - Garlic attenuates nitric oxide production in rat cardiac myocytes through
      inhibition of inducible nitric oxide synthase and the arginine transporter CAT-2
      (cationic amino acid transporter-2).
AB  - It is now accepted that allicin, the main biologically active compound in garlic,
      exhibits antioxidant activity. The present study was designed to test the
      hypothesis that the antioxidant activity of garlic can be partially attributed to
      the inhibition of nitric oxide (NO) production by cytokine-induced NO synthase
      (iNOS). Cardiac myocytes cultured from neonatal Wistar rats were stimulated by
      lipopolysaccharide (LPS) and incubated for 24 h with various concentrations of
      allicin. This resulted in marked inhibition of nitrite production. Interestingly,
      a low concentration of allicin (10 microM) was significantly more potent in
      abrogating the effect of LPS on nitrite production than a higher concentration
      (40 microM). Allicin decreased steady-state iNOS mRNA levels, and this effect was
      maximal when a lower concentration was used (10 microM compared with 40 microM).
      In order to explore additional effects of allicin on NO generation that might
      counteract the effect on iNOS, we assessed the effects of higher allicin
      concentrations on arginine transport. Allicin inhibited the uptake of 1 mM
      extracellular arginine in a concentration-dependent manner. The expression of the
      two arginine transporters that are expressed in cardiac myocytes [CAT-1 (cationic
      amino acid transporter-1) and CAT-2] was studied using reverse transcription-PCR.
      A concentration of 200 microM allicin abolished the expression of CAT-2 mRNA, 100
      microM significantly attenuated it, whereas 50 microM had no effect. Allicin had
      no effect on steady-state CAT-1 mRNA levels. Our results suggest that allicin
      inhibits iNOS activity through two different mechanisms: at lower concentrations
      it decreases iNOS mRNA levels, whereas at higher concentrations it inhibits
      arginine transport through down-regulation of CAT-2 mRNA.

PMID- 11980566
TI  - Acute haemodynamic effects of lipolysis-induced increase of free fatty acids in
      healthy men.
AB  - Circulating free fatty acids (FFA) are elevated in subjects with insulin
      resistance and Type II diabetes, and increase during myocardial ischaemia, but
      their haemodynamic effects are incompletely understood. During an investigation
      of the effects of FFA on endothelial function, we administered lipid emulsion
      (150 mg x min(-1) of soybean oil) with heparin (0.2 unit x kg(-1) x min(-1))
      intravenously to eight healthy men for 2 h. This increased circulating FFA to
      3.1+/-0.5 mmol/l. Forearm blood flow was measured by venous occlusion
      plethysmography during brachial artery infusions of saline, acetylcholine and
      nitroprusside before, and at 1 and 2 h. Lipid/heparin infusion had no significant
      effect on vasodilation to nitroprusside but progressively increased responses to
      acetylcholine (from 6.3+/-2.0 during 30 microg x min(-1) before-lipid infusion to
      7.9+/-1.3 at 1 h and 12.2+/-1.1 ml x min(-1) x 100 ml(-1) at 2 h, P<0.001). Basal
      flow increased from 2.7+/-0.7 to 4.7+/-0.8 ml x min(-1) x 100 ml(-1) from 0 to 2
      h. We performed a second study to clarify this effect on basal blood flow.
      Healthy men (n=8) received, on separate occasions, 4 h intravenous infusions of
      lipid emulsion with heparin and, as a control, saline with heparin. Lipid with
      heparin increased mean arterial blood pressure (maximum increment 8.2+/-2.7 mm
      Hg, P<0.01 compared with saline/heparin control) and forearm blood flow (from
      1.7+/-0.2 to 2.9+/-0.3 ml x min(-1) x 100 ml(-1), P<0.01) without a significant
      effect on heart rate, and reduced calculated forearm vascular resistance (from
      49.1+/-5.4 to 31.3+/-3.9 arbitrary units, P<0.01). In conclusion, acute elevation
      of FFA in healthy men increases arterial blood pressure and reduces vascular
      resistance. These haemodynamic changes could be clinically relevant.

PMID- 11980567
TI  - A new ferrochelatase mutation combined with low expression alleles in a Japanese
      patient with erythropoietic protoporphyria.
AB  - We investigated the molecular defect of the ferrochelatase gene in a Japanese
      patient with erythropoietic protoporphyria (EPP), and identified a novel 16 base
      pair (574-589) deletion within exon 5. This deletion resulted in a frame-shift
      mutation and created a premature stop codon at amino acid position 198. The same
      molecular defect was also identified in his mother and a brother who had
      symptomatic EPP, but not in his father who was asymptomatic. The subjects with
      EPP were homozygous for the low expression haplotype, while his father was
      heterozygous for this haplotype. These results indicate that the combination of a
      16 base pair deletion and low expression of the wild-type allelic variant is
      responsible for EPP in this pedigree.

PMID- 11980568
TI  - Type I IgE receptor, interleukin 4 receptor and interleukin 13 polymorphisms in
      children with nephrotic syndrome.
AB  - Polymorphisms in the genes encoding the high-affinity IgE receptor, the
      interleukin 4 (IL4) receptor and IL13 can be associated with the development of
      asthma and allergy. Although several studies have described an association
      between atopy and idiopathic childhood nephrotic syndrome (NS), it is not clear
      whether this association is of a causal nature. Furthermore, it is not known
      whether these polymorphisms are associated with the clinical course of NS. A
      total of 84 children (52 male and 32 female; mean age 12.1 years) with NS were
      included in the present study. Of these, 78 could be classified as either atopic
      or non-atopic. Atopy was defined by elevated IgE levels (>100 k-units/l) and/or a
      positive history of atopy (33 of 78 patients). DNA was extracted from blood
      collected in EDTA tubes, and polymorphisms at positions 50 and 551 of the IL4
      receptor, position 110 of IL13 and position 181 of the high-affinity IgE receptor
      were investigated by sequence-specific PCR or direct sequencing. Although we
      noted a strong tendency towards a higher allele frequency of polymorphisms in
      children with atopy and NS compared with children with NS but without atopy (IL4
      50, 30% compared with 18%; IL4 551, 39% compared with 31%; IL13 110, 45% compared
      with 33%; IgE 181, 12% compared with 13%), these differences did not reach
      statistical significance. There were no differences in the frequency of
      polymorphisms between the different clinical courses of NS (frequent relapsers,
      steroid-dependent or steroid-resistant NS). We conclude that polymorphisms in the
      IL4 receptor, the high-affinity IgE receptor and IL13 do not seem to predict the
      clinical course of NS, despite the fact that serum IgE elevations are more
      frequent in patients with NS than in normal control subjects. The investigated
      polymorphisms may contribute to the IgE switch in patients with NS.

PMID- 11980569
TI  - Cytokine polymorphisms and nephrotic syndrome.

PMID- 11980570
TI  - Left ventricular long-axis changes in early diastole and systole: impact of
      systolic function on diastole.
AB  - Impaired long-axis motion is a sensitive marker of systolic myocardial
      dysfunction, but no data are available that relate long-axis changes in systole
      with those in diastole, particularly in subjects with diastolic dysfunction and a
      'normal' left ventricular (LV) ejection fraction. A total of 311 subjects
      (including 105 normal healthy volunteers) aged 20-89 years with variable degrees
      of systolic function (LV ejection fraction range 0.15-0.84) and diastolic
      function were studied using tissue Doppler echocardiography and M-mode
      echocardiography to determine mean mitral annular amplitude and peak velocity in
      systole and early and late diastole. The LV systolic mitral annular amplitude
      (S(LAX), where LAX is long-axis amplitude) and peak velocity (S(m)) correlated
      well with the respective early diastolic components (E(LAX) and E(m)) and late
      diastolic (atrial) components (A(LAX) and A(m)). A non-linear equation fitted
      better than a linear relationship (non-linear model: S(LAX) against E(LAX),
      r(2)=0.67; S(m) against E(m), r(2)=0.60; S(LAX) against A(LAX) and S(m) against
      A(m), r(2)=0.42). After adjusting for age, sex and heart rate, linear
      relationships of early diastolic (E(LAX), r(2)=0.70; E(m), r(2)=0.60) and late
      diastolic (A(LAX), r(2)=0.61; A(m), r(2)=0.64) long-axis amplitudes and
      velocities with the respective values for S(LAX) and S(m) were found, even in
      those subjects with apparently 'isolated' diastolic dysfunction. Long-axis
      changes in systole or diastole did not correlate with Doppler mitral velocities.
      We conclude that ventricular long-axis changes in early diastole are closely
      related to systolic function, even in subjects with diastolic dysfunction. 'Pure'
      or isolated diastolic dysfunction is uncommon.

PMID- 11980571
TI  - Carbohydrate ingestion, with transient endogenous insulinaemia, produces both
      sympathetic activation and vasodilatation in normal humans.
AB  - It has been shown that sustained insulin infusion causes an increase in
      sympathetic vasoconstrictor discharge but, despite this, also causes peripheral
      vasodilatation. The present study was designed to determine in healthy subjects
      the effect of ingestion of a carbohydrate meal, with its attendant physiological
      insulinaemia, on vascular resistance in and sympathetic vasoconstrictor discharge
      to the same vascular bed, and the relationship between these parameters. Fifteen
      healthy subjects were studied for 2 h following ingestion of a carbohydrate meal.
      Calf vascular resistance was measured by venous occlusion plethysmography, and
      muscle sympathetic nerve activity was assessed by peroneal microneurography. Five
      of the subjects also ingested water on a separate occasion, as a control.
      Following the carbohydrate meal, the serum insulin concentration increased to
      588+/-72 pmol/l. This was associated with a 47% increase in skeletal muscle blood
      flow (P<0.001), a 39% fall in vascular resistance (P<0.001) and a 57% increase in
      sympathetic activity (P<0.001). There was a significant correlation between the
      increase in insulin and the changes in blood flow, vascular resistance and
      sympathetic activity. In conclusion, we have shown that ingestion of a
      carbohydrate meal, with its attendant physiological insulinaemia, was associated
      with overriding skeletal muscle vasodilatation, despite an increase in
      sympathetic vasoconstrictor discharge to the same vascular bed. These mechanisms
      may be important in ensuring optimal glucose uptake and maintenance of blood
      pressure postprandially.

PMID- 11980572
TI  - Muscle function during repetitive moderate-intensity muscle contractions in
      myoadenylate deaminase-deficient Dutch subjects.
AB  - We investigated whether the capacity for repetitive submaximal muscle contraction
      was reduced in a group of subjects (n=8) with a primary deficiency of
      myoadenylate deaminase (MAD). Quadriceps femoris muscle fatigue was evaluated
      using voluntary and electrically stimulated contractions during 20 min of
      repetitive voluntary isometric contractions at 40% of maximal force-generating
      capacity (MFGC). After 5 min of exercise, MFGC had declined significantly to
      70.6+/-4.1% (mean+/-S.E.M.) and 87.2+/-1.6% of baseline values in MAD-deficient
      and sedentary control subjects (n=8) respectively (P=0.002 between groups). After
      5 min of exercise, the half-relaxation time had increased significantly to
      113.4+/-6.1% of baseline in MAD-deficient muscle, but had decreased significantly
      to 94.1+/-1.3% in control subjects (P=0.003 between groups). All control subjects
      completed the 20-min exercise test. Five of the MAD-deficient subjects had to
      stop exercising due to early muscle fatigue; however, three of the MAD-deficient
      subjects were able to complete the 20-min exercise test. In conclusion, although
      the capacity for repetitive submaximal isometric muscle contractions for the
      group of MAD-deficient subjects was significantly decreased, it remains uncertain
      whether MAD deficiency is the sole cause of pronounced muscle fatigue.

PMID- 11980573
TI  - Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo.
AB  - The non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used group of
      drugs in clinical medicine. However, their propensity to cause gastrointestinal
      damage limits their clinical utility. The pathogenesis of this toxicity is not
      well established. It has been postulated that an early event in the development
      of damage is an effect of these drugs on mitochondrial function. The present
      paper sets out to evaluate the effects of indomethacin, a commonly used NSAID, on
      energy metabolism in vivo. Indomethacin was administered to male Sprague-Dawley
      rats, either intrajejunally or orally, and indices of mitochondrial function were
      determined. The parameters chosen for this purpose were oxygen uptake by, lactate
      levels in and the energy charge of jejunal tissue. Oxygen uptake by and energy
      charge in jejunal tissue were unaffected at 1 and 3 h after dosing by gavage with
      indomethacin. The drug significantly affected the tissue lactate/pyruvate ratio
      at 3 h (but not at 1 h) after oral dosing. Effects of indomethacin on jejunum
      incubated ex vivo were found to be reversible. The data suggest that indomethacin
      affects mitochondrial function in vivo, but that compensatory changes in
      glycolytic rate maintain energy charge.

PMID- 11980574
TI  - Circadian variation in vascular tone and endothelial cell function in normal
      males.
AB  - The existence of circadian rhythms in the time of onset of acute cardiovascular
      events has been described previously. This report describes the circadian
      variation in endothelial cell products, such as nitric oxide (NO) and endothelin
      1 (ET-1) levels, and endothelium-dependent and -independent vasodilation in
      normal males. Plasma ET-1 and NO were measured every 4 h in nine subjects (20-41
      years old) over a 24 h period. Endothelium-dependent and -independent vascular
      responses were measured in the forearm skin every 4 h using laser Doppler imaging
      after iontophoresis of increasing doses of acetylcholine (ACh) and sodium
      nitroprusside respectively. A statistically significant circadian variation was
      demonstrated for the mean ACh response (P=0.0001, ANOVA). The peak response [in
      arbitrary perfusion units (AU)] occurred at 16.00 hours (8.90+/-1.91 AU) and the
      lowest response at 08.00 hours (4.57+/-0.66 AU). A significant circadian
      variation was also seen for the highest dose of sodium nitroprusside (P=0.036,
      ANOVA), the peak occurred at 16.00 hours (3.97+/-1.80 AU), and the lowest at
      04.00 hours (2.62+/-0.58 AU) and 08.00 hours (2.58+/-1.16 AU). There was a
      significant circadian variation in the ET-1 levels (P=0.04) with two peaks, one
      at 20.00 hours (0.80+/-0.28 pg/ml) and the other at 08.00 hours (0.84+/-0.15
      pg/ml). The lowest value occurred at 16.00 hours (0.61+/-0.24 pg/ml). There was
      also a borderline trend for a circadian variation in NO levels (P=0.06), with
      higher levels at 20.00 hours (15.53+/-8.42 micromol/l), and low levels at 04.00
      hours (10.87+/-4.70 micromol/l) and 08.00 hours (9.82+/-3.15 micromol/l). ACh
      responses were significantly correlated with ET-1 (r=-0.3, P=0.02) and NO
      (r=0.30, P=0.02) levels. Our findings suggest that endothelial activity has a
      circadian variation with attenuation in the morning. These circadian variations
      in endothelial activity might play an important role in the occurrence of acute
      cardiovascular events at this time, which are precipitated through the interplay
      between ET-1, NO and vascular function.

PMID- 11980575
TI  - Low-protein diet impairs vascular relaxation in virgin and pregnant rats.
AB  - Pregnancy is associated with increases in maternal cardiac output and plasma
      volume and a reduction in peripheral vascular resistance. Cardiac output and
      plasma volume are substantially reduced in pregnant rats fed a low-protein diet,
      but it is not known whether vascular function is also compromised. We have
      investigated vascular function in virgin and pregnant Wistar rats subjected to
      dietary protein restriction [9% (w/v) casein, compared with 18% (w/v) casein for
      controls]. The diets were fed to the groups for 18 days; in the pregnant rats,
      the diets were given from day 1 of pregnancy. Branches of the mesenteric arteries
      were studied on day 18 of the dietary period using myography. Significant
      reductions in sensitivity to acetylcholine occurred in vessels from virgin
      (P=0.04) and pregnant (P=0.01) rats that had consumed the 9% casein diet. In
      arteries from the virgin rats on the restricted diet there was also a significant
      reduction in sensitivity (P=0.0003) and maximum relaxation (P=0.009) to the NO
      donor spermine NONOate. Mean placental and fetal weights were significantly lower
      in the rats fed on 9% casein (P<0.0001 and P=0.005 respectively). Thus low
      protein diets impair vasodilator responses in female rats. These effects may
      contribute to the poor cardiovascular adaptation to pregnancy and lower fetal
      weights associated with restricted protein intake.

PMID- 11980576
TI  - Evaluation of four different methods to measure endothelium-dependent
      vasodilation in the human peripheral circulation.
AB  - At present, several techniques exist that claim to evaluate endothelium-dependent
      vasodilation (EDV) in the human peripheral circulation. The present study aims to
      evaluate the relationships between four of these techniques. A group of 24 young,
      healthy subjects underwent measurements of EDV and endothelium-independent
      vasodilation (EIDV) in predominately resistance vessels in the forearm using the
      invasive forearm technique with local infusion of methacholine and sodium
      nitroprusside, evaluation of flow-mediated vasodilation (FMD) in the conduit
      brachial artery measured by ultrasound, with or without the addition of ischaemic
      hand exercise, and evaluation of the reduction in the relative height of the
      inflection point of the radial pulse wave following beta(2)-adrenergic receptor
      stimulation. The reduction in the relative height of the inflection point
      following beta(2)-adrenergic receptor stimulation was significantly related to
      both EDV and EIDV in the forearm (r=-0.41 and r=-0.42 respectively; both P<0.05),
      but not to the EDV/EIDV ratio (r=-0.10). However, FMD, with or without the
      addition of ischaemic hand exercise, was not significantly related to the results
      obtained using the other two techniques (r=-0.18 to +0.13). In conclusion, the
      reduction in the relative height of the inflection point of the pulse wave
      following beta(2)-adrenergic receptor stimulation was related to both EDV and
      EIDV measured by the invasive forearm technique, indicating that the pulse wave
      technique does not measure EDV specifically. FMD in the brachial artery, with or
      without ischaemic hand exercise, was not significantly related to values obtained
      using the other two techniques, indicating that endothelial function differs
      between conduit and resistance arteries, and that both of these measurements
      should be evaluated in future studies.

PMID- 11980577
TI  - The effect of rate of weight loss on erythrocyte glutathione concentration and
      synthesis in healthy obese men.
AB  - Obesity is commonly associated with a high incidence and prevalence of
      dyslipidaemia, cardiovascular disease and Type II diabetes. Interestingly,
      studies have also reported decreased antioxidant levels in obese subjects. This
      may constitute an independent risk factor in the pathogenesis of coronary artery
      disease as obese subjects would have a decreased capacity to prevent the
      oxidative modification of low-density lipoproteins, which is a mechanism
      suggested as central to the development of atherogenesis. As part of a study to
      investigate responses to weight loss, we have assessed the effects on GSH status
      of a decrease in body mass of 5%, either after 6 days of complete starvation or
      11 days of a very low calorie diet (2.55 MJ/day). There were significant
      differences between the two groups in the synthesis rate of erythrocyte GSH in
      response to weight loss. Both the fractional and the erythrocyte synthesis rate
      of GSH decreased significantly (P<0.01) in the starvation group by 22% and 16%
      respectively. In contrast, no change in synthesis rates was observed in the very
      low calorie diet group (P>0.05). Total erythrocyte concentration of GSH was
      unaffected by the weight loss within both groups. These results suggest that
      erythrocyte GSH synthesis is depressed in response to a very rapid weight loss
      induced by fasting. An acute reduction in GSH synthesis in response to a rapid
      weight loss may constitute a risk factor during periods of increased GSH demands.

PMID- 11980578
TI  - Effects of hepatic ischaemia/reperfusion injury in a rabbit model of Indocyanine
      Green clearance.
AB  - Hepatic ischaemia/reperfusion (I/R) injury is a major cause of primary non
      function of the graft after liver transplantation. The ability to assess the
      severity of ischaemic injury would be of prognostic value and allow the
      possibility of therapeutic interventions. Currently there is no reliable clinical
      method for assessing the severity of hepatic ischaemic injury. The hepatic
      handling of Indocyanine Green as a technique for monitoring the severity of I/R
      injury has been investigated in the present study. A rabbit model of lobar
      ischaemia was used. At laparotomy, left lobe hepatic ischaemia was produced for
      30, 45 or 60 min, followed by 60 min of reperfusion. Liver function tests, bile
      excretion and flow in the hepatic microcirculation were measured in animals
      subjected to I/R injury and in controls. Indocyanine Green was given after
      reperfusion and its concentration was measured directly in the liver using near
      infrared spectroscopy. Indocyanine Green hepatic uptake and excretion rates were
      calculated. I/R injury produced significant increases in hepatic serum enzymes
      and decreases in bile excretion and hepatic microcirculation in all I/R groups in
      comparison with controls. There was a significant reduction in Indocyanine Green
      uptake and excretion in the I/R groups in comparison with controls, which was
      correlated with the duration of ischaemia. Indocyanine Green uptake was
      correlated significantly with flow in the hepatic microcirculation, and its
      excretion was correlated significantly with the severity of liver damage, as
      reflected by the changes in serum enzymes and bile excretion. In conclusion, I/R
      injury affects the hepatic handling of Indocyanine Green, and direct
      quantification of the uptake and excretion of this dye by near-infrared
      spectroscopy may be used to objectively assess the degree of I/R injury.

PMID- 11980579
TI  - Relationship between asymptomatic hypercholanaemia of pregnancy and progesterone
      metabolism.
AB  - The aim of this study was to identify a subgroup of pregnant women with
      asymptomatic hypercholanaemia of pregnancy (AHP), in which the relationship
      between alterations in the level and pattern of serum bile acids (BAs) and of
      progesterone plus progesterone metabolites could be investigated in the absence
      of overt impairment of hepatobiliary function. Cholanaemia and serum
      concentrations of progesterone were assayed by an enzymic technique and by ELISA
      respectively, while BA molecular species and progesterone metabolites were
      measured by GC-MS, in the serum of 411 healthy pregnant women. Samples were
      collected after an overnight fast in the final week of each trimester of
      gestation. Two pregnant women were excluded because of the suspicion of
      intrahepatic cholestasis of pregnancy (ICP). Cholanaemia was found to increase
      progressively throughout pregnancy, but with normal mean values lower than 3.0
      microM. Thus in our series AHP was defined arbitrarily as the presence of serum
      total BA concentrations 2-fold higher than this value, i.e. 6 microM, in the
      absence of hepatobiliary disease or symptoms of ICP. The prevalence of this
      condition was observed to increase with gestational age. Changes in the pattern
      of serum BAs in AHP were also found. These were reflected in a marked increase in
      the proportion of cholic acid together with a decrease in that of deoxycholic
      acid, while the proportions of chenodeoxycholic acid and lithocholic acid changed
      only moderately. When groups at the same gestational age were compared, serum
      progesterone levels were always significantly lower, while those of progesterone
      metabolites were higher, in women with AHP. Our results suggest that AHP is a
      relatively common condition in our geographical location, where ICP is rarely
      diagnosed. Changes in the serum BA pattern in hypercholanaemia resemble these
      described in ICP. The simultaneous finding of lower serum total progesterone
      levels along with an increase in its metabolites supports the hypothesis that a
      primary defect in progesterone metabolism may be involved in the aetiology of
      ICP.

PMID- 11980580
TI  - Ageing is associated with impairment of nitric oxide and prostanoid dilator
      pathways in the human forearm.
AB  - Ageing is associated with endothelial dysfunction and increased cardiovascular
      risk. We assessed the activity of nitric oxide (NO) and prostaglandin pathways in
      older subjects. Bilateral venous occlusion plethysmography was used to measure
      forearm blood flow during intra-arterial infusion of the NO synthase inhibitor,
      N(G)-monomethyl--arginine (-NMMA; 1, 2 and 4 micromol/min), the cyclo-oxygenase
      inhibitor, aspirin (3, 9 and 30 micromol/min), and the smooth muscle constrictor,
      noradrenaline (60, 120 and 240 pmol/min); each dose infused for 5 min. Eighteen
      young and 15 healthy older subjects (mean age+/-S.E.M., 32+/-1 and 65+/-1 years
      respectively) were studied. Effects of treatment were calculated from the ratio
      of blood flow in the infused to control arm, expressed as a percentage. Dose
      response curves were compared by analysis of the area under the curve (AUC) using
      independent samples t test. All agents caused dose-dependent decreases in basal
      forearm blood flow. AUC values for noradrenaline, aspirin and -NMMA in younger
      and older subjects were 162+/-24, 173+/-24 and 170+/-17, and 138+/-22, 70+/-22
      and 89+/-22 respectively. Effects of aspirin and -NMMA, but not noradrenaline,
      were reduced in older subjects (P=0.004, 0.007 and 0.461 respectively). Our
      findings suggest a generalized abnormality of basal endothelial function in older
      people, with similar impairment of NO and prostanoid dilator pathways. Defects in
      both pathways could contribute to the development of age-related cardiovascular
      disease.

PMID- 11980581
TI  - Vascular ageing.

PMID- 11980582
TI  - Internet hand x-rays: A comparison of joint space narrowing and erosion scores
      (Sharp/Genant) of plain versus digitized x-rays in rheumatoid arthritis patients.
AB  - BACKGROUND: The objective of the study is to examine the reliability of erosion
      and joint space narrowing scores derived from hand x-rays posted on the Internet
      compared to scores derived from original plain x-rays. METHODS: Left and right x
      rays of the hands of 36 patients were first digitized and then posted in standard
      fashion to a secure Internet website. Both the plain and Internet x-rays were
      scored for erosions and joint space narrowing using the Sharp/Genant method. All
      scoring was completed in a blind and randomized manner. Agreement between plain
      and Internet x-ray scores was calculated using Lin's concordance correlations and
      Bland-Altman graphical representation. RESULTS: Erosion scores for plain x-rays
      showed almost perfect concordance with x-rays read on the Internet (concordance
      0.887). However, joint space narrowing scores were only "fair" (concordance
      0.365). Global scores demonstrated substantial concordance between plain and
      Internet readings (concordance 0.769). Hand x-rays with less disease involvement
      showed a tendency to be scored higher on the Internet versions than those with
      greater disease involvement. This was primarily evident in the joint space
      narrowing scores. CONCLUSIONS: The Internet represents a valid medium for
      displaying and scoring hand x-rays of patients with RA. Higher scores from the
      Internet version may be related to better viewing conditions on the computer
      screen relative to the plain x-ray viewing, which did not include magnifying lens
      or bright light. The capability to view high quality x-rays on the Internet has
      the potential to facilitate information sharing, education, and encourage
      collaborative studies.

PMID- 11980583
TI  - The method of bladder drainage in spinal cord injury patients may influence the
      histological changes in the mucosa of neuropathic bladder - a hypothesis.
AB  - BACKGROUND: In spinal cord injury (SCI) patients, no correlation was found
      between the number of bladder infections per year, the period since injury, the
      neurologic level of the spinal cord lesion and the histopathology of the urinary
      bladder mucosa. The use of chronic indwelling urethral and/or suprapubic
      catheters in SCI patients is often associated with inflammatory and proliferative
      pathological conditions in neuropathic bladder. PRESENTATION OF THE HYPOTHESIS:
      We propose a hypothesis that the type of bladder drainage in SCI patients
      influences the histological changes in the mucosa of neuropathic bladder. This
      hypothesis implies that SCI patients with long-term indwelling urinary catheters
      develop certain histological changes in bladder mucosa, which are seen less
      frequently in SCI patients, who do not use long-term indwelling catheters. The
      latter group includes patients, who perform regular intermittent catheterisation
      and those, who wear a penile sheath and empty their bladders satisfactorily by
      reflex voiding. We hypothesise that the following histological lesions are seen
      more frequently in the neuropathic bladder of SCI patients with long-term
      indwelling catheters.(1) Papillary or polypoid cystitis; (2) widespread cystitis
      glandularis; (3) moderate to severe, acute and chronic inflammatory changes in
      bladder mucosa; (4) follicular cystitis; (5) squamous metaplasia; and (6)
      urothelial dysplasia. As per this hypothesis, it is postulated that the above
      pathological conditions are seen less often in SCI patients, who achieve
      complete, low-pressure emptying of the neuropathic bladder by regular
      intermittent catheterisation, and SCI patients with penile sheath drainage, who
      empty their bladders satisfactorily by reflex voiding. TESTING THE HYPOTHESIS: A
      large prospective study of bladder biopsies in SCI patients practising different
      methods of bladder drainage is required to validate this hypothesis that the
      histological changes in bladder mucosa are related to the method of bladder
      drainage in SCI patients. IMPLICATIONS OF THE HYPOTHESIS: We propose a hypothesis
      that the method of bladder drainage in SCI patients influences histological
      changes in the bladder mucosa. If this hypothesis is validated, methods of
      bladder drainage such as intermittent catheterisation, which do not require the
      use of chronic indwelling catheters, should be recommended, in order to minimise
      adverse histological changes in the mucosa of neuropathic bladder of spinal cord
      injury patients.

PMID- 11980584
TI  - Genetic polymorphisms in lung disease: bandwagon or breakthrough?
AB  - The study of genetic polymorphisms has touched every aspect of pulmonary and
      critical care medicine. We review recent progress made using genetic
      polymorphisms to define pathophysiology, to identify persons at risk for
      pulmonary disease and to predict treatment response. Several pitfalls are
      commonly encountered in studying genetic polymorphisms, and this article points
      out criteria that should be applied to design high-quality genetic polymorphism
      studies.

PMID- 11980585
TI  - Focusing on diffuse (interstitial) lung disease: a rapidly evolving field.

PMID- 11980586
TI  - Altered prostanoid production by fibroblasts cultured from the lungs of human
      subjects with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Prostanoids are known to participate in the process of fibrogenesis.
      Because lung fibroblasts produce prostanoids and are believed to play a central
      role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), we hypothesized
      that fibroblasts (HF) cultured from the lungs of patients with IPF (HF-IPF) have
      an altered balance between profibrotic (thromboxane [TX]A2) and antifibrotic
      (prostacyclin [PGI2]) prostaglandins (PGs) when compared with normal human lung
      fibroblasts (HF-NL). METHODS: We measured inducible cyclooxygenase (COX)-2 gene
      and protein expression, and a profile of prostanoids at baseline and after IL
      1beta stimulation. RESULTS: In both HF-IPF and HF-NL COX-2 expression was
      undetectable at baseline, but was significantly upregulated by IL-1beta. PGE2 was
      the predominant COX product in IL-1beta-stimulated cells with no significant
      difference between HF-IPF and HF-NL (28.35 [9.09-89.09] vs. 17.12 [8.58-29.33]
      ng/10(6) cells/30 min, respectively; P = 0.25). TXB2 (the stable metabolite of
      TXA2) production was significantly higher in IL-1beta-stimulated HF-IPF compared
      to HF-NL (1.92 [1.27-2.57] vs. 0.61 [0.21-1.64] ng/10(6) cells/30 min,
      respectively; P = 0.007) and the ratio of PGI2 (as measured by its stable
      metabolite 6-keto-PGF1alpha) to TXB2 was significantly lower at baseline in HF
      IPF (0.08 [0.04-0.52] vs. 0.12 [0.11-0.89] in HF-NL; P = 0.028) and with IL-1beta
      stimulation (0.24 [0.05-1.53] vs. 1.08 [0.51-3.79] in HF-NL; P = 0.09).
      CONCLUSION: An alteration in the balance of profibrotic and antifibrotic PGs in
      HF-IPF may play a role in the pathogeneses of IPF.

PMID- 11980587
TI  - Binding of protegrin-1 to Pseudomonas aeruginosa and Burkholderia cepacia.
AB  - BACKGROUND: Pseudomonas aeruginosa and Burkholderia cepacia infections of cystic
      fibrosis patients' lungs are often resistant to conventional antibiotic therapy.
      Protegrins are antimicrobial peptides with potent activity against many bacteria,
      including P. aeruginosa. The present study evaluates the correlation between
      protegrin-1 (PG-1) sensitivity/resistance and protegrin binding in P. aeruginosa
      and B. cepacia. METHODS: The PG-1 sensitivity/resistance and PG-1 binding
      properties of P. aeruginosa and B. cepacia were assessed using radial diffusion
      assays, radioiodinated PG-1, and surface plasmon resonance (BiaCore). RESULTS:
      The six P. aeruginosa strains examined were very sensitive to PG-1, exhibiting
      minimal active concentrations from 0.0625-0.5 microg/ml in radial diffusion
      assays. In contrast, all five B. cepacia strains examined were greater than 10
      fold to 100-fold more resistant, with minimal active concentrations ranging from
      6-10 microg/ml. When incubated with a radioiodinated variant of PG-1, a sensitive
      P. aeruginosa strain bound considerably more protegrin molecules per cell than a
      resistant B. cepacia strain. Binding/diffusion and surface plasmon resonance
      assays revealed that isolated lipopolysaccharide (LPS) and lipid A from the
      sensitive P. aeruginosa strains bound PG-1 more effectively than LPS and lipid A
      from resistant B. cepacia strains. CONCLUSION: These findings support the
      hypothesis that the relative resistance of B. cepacia to protegrin is due to a
      reduced number of PG-1 binding sites on the lipid A moiety of its LPS.

PMID- 11980588
TI  - Lung surfactant in subacute pulmonary disease.
AB  - Pulmonary surfactant is a surface active material composed of both lipids and
      proteins that is produced by alveolar type II pneumocytes. Abnormalities of
      surfactant in the immature lung or in the acutely inflamed mature lung are well
      described. However, in a variety of subacute diseases of the mature lung,
      abnormalities of lung surfactant may also be of importance. These diseases
      include chronic obstructive pulmonary disease, asthma, cystic fibrosis,
      interstitial lung disease, pneumonia, and alveolar proteinosis. Understanding of
      the mechanisms that disturb the lung surfactant system may lead to novel rational
      therapies for these diseases.

PMID- 11980590
TI  - The organization of hospital infection control committees and their importance in
      Brazil.
AB  - The importance of Hospital Infection Control Committees (HICC) increases every
      year due to the emergence of multiresistant bacterial strains, hospital
      outbreaks, and other factors that cause HI. This demonstrates the fragility of
      the quality of hospital and medical care. Having a well-organized HICC benefits
      hospitals by improving quality, lowering costs and, most important, reducing
      patient morbidity and mortality. This review records the history of the
      development of HICCs, their present organizational structure, and offers
      recommendations for hte best methods of infection surveillance.

PMID- 11980589
TI  - Preneoplastic lesions of the lung.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. If we can define and
      detect preneoplastic lesions, we might have a chance of improving survival. The
      World Health Organization has defined three preneoplastic lesions of the
      bronchial epithelium: squamous dysplasia/carcinoma in situ; atypical adenomatous
      hyperplasia; and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.
      These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma
      and carcinoid tumors, respectively. In this review we summarize the data
      supporting the preneoplastic nature of these lesions, and delve into some of the
      genetic changes found in atypical adenomatous hyperplasia and squamous
      dysplasia/carcinoma in situ.

PMID- 11980591
TI  - Antimicrobial resistance in respiratory pathogens isolated in Brazil during 1999
      2000.
AB  - The in vitro antimicrobial susceptibility of the respiratory pathogens
      Streptococcus Pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis to
      commonly tested and prescribed agents was investigated during 1999-2000 and
      compared with results obtained during a previous 1997-1998 study. Of 448 isolates
      of S. Pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9%
      were intermediate, and 2.9% were resistant to penicillin, demonstrating that
      there were no major changes in susceptibility to penicillin from 1997-1998 (77.1%
      susceptible, 18.7% intermediate, 4.2% resistant). All S. Pneumoniae isolates from
      1999-2000 were susceptible to levofloxacin and vancomycin and >90% were
      susceptible to the B-lactams (amoxicillin-clavulanate, ceftriaxone, and
      cefuroxime) and macrolides (axithyromycin and clarithromycin), showing that
      susceptibility to these agents also remained unchanged since 1997-1998. The most
      notable increase in resistance between the two studies was demonstrated by
      trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin
      resistance correlated with resistance to B-lactams, macrolides, and trimethoprim
      sulfamethoxazole in both studies. In H. influenzae, the prevalence of B-lactamase
      producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998).
      All H. influenzae isolates were susceptible to levofloxacine, ceftriaxone,
      cefuroxime, and azithromycin, and showed no change between the two studies.
      Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999
      2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of B-lactamase
      producing isolates was unchanged (97.9% in 1999-2000;98.0% in 1997-1998). The
      most active agents against M. catarrhalis were azithromycin (MIC(90),< or = 0.03
      microg/ml) and levofloxacin (MIC(90),< or = 0.03 microg/ml). Overall, these
      results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been
      no significant changes in the susceptibility of respiratory pathogens to any of
      the commonly tested and prescribed agents with the exception of trimethoprim
      sulfamethoxazole for S. Pneumoniae.

PMID- 11980592
TI  - Susceptibility of S. pneumoniae to various antibiotics aong strains isolated from
      patients and healthy carriers in different regions of Brazil(1999-2000).
AB  - Resistance of microbes to commonly used antibiotics became a major concern at the
      end of the last century. Because Streptococcus pneumoniae is the most common
      pathogen in respiratory infections, we conducted microbiological assessment of
      drug susceptibility patterns among strains collected from two different
      population groups: 1) adult and pediatric patients (375 isolates) with different
      infections, and 2) healthy children in day care centers (<5 years old; 350
      isolates). High level resistance to penicillin was not identified in either
      group. Intermediate resistance levels were similar in both groups (adults: 9.9%;
      children: 9.2%). The Central West region of Brazil tended to have lower
      susceptibility of S. Pneumoniae from infected adults and children to penicillin
      (81% vs. 93% in the South and 90% in the Southeast), tetracycline (64% vs. 80%
      and 76%), and trimethoprim/sulfamethoxazole (14% vs. 34%). Susceptibility was
      similar among strains from nasal cultures of healthy children tested in each of 4
      regions of Brazil. All isolates were susceptible to cefaclor, cefotaxime and
      amoxacillin/clavulanate. This study, in two distinct populations, allowed
      characterization of local microbiological resistance patterns. This data is
      expected to be of use in guiding empiric therapy in the different regions of
      Brazil.

PMID- 11980594
TI  - Chronic ulcers and myasis as ports of entry for Clostridium tetani.
AB  - Evaluating tetanus immune status is not yet the usual clinical practice regarding
      patients with chronic ulcers or myasis. However, of 858 tetanus patients at
      Hospital Couto Maia (Salvador, Bahia, Brazil) aged 1 year or above, 2 had
      pressure ulcers and 17 had chronic ulceration of the lower limbs where these skin
      lesions were the ports of entry for Clostridium tetani. In these 19 cases, the
      following predisposing factors were described: venous insufficiency (n=6), sickle
      cell anemia (n=2), Hansen s disease (n=1), malnutrition (n=1), diabetes mellitus
      (n=1), trauma (n=1) and unknown factors (n=7). In 6 other cases, in addition to
      the Hansen s disease patient, the port of entry for tetanus was the site of
      extraction of Tunga penetrans larvae. In these 25 cases, the majority of patients
      (68%) were over 40 years old (17/25) and all of these patients stated that they
      had either not followed a tetanus toxoid vaccination regimen (19/25), or had
      partially completed such a regimen, or did not give precise information (6/25).
      Among the same series studied, over half (52%) of the patients died (13/25). We
      conclude that tetanus prevention must be included in the treatment of chronic
      skin ulcer patients, vaccination coverage should be increased among older people,
      and strategies aimed at improving coverage for all age groups must be reviewed.

PMID- 11980593
TI  - Hospital-associated funguria: analysis of risk factors, clinical presentation and
      outcome.
AB  - Fungal urinary tract infections are an increasing problem in hospitalized
      patients. Funguria may be a result of contamination of the urine specimen,
      colonization of hte urinary tract, or may be indicative of true invasive
      infection. In this study, we report the risk factors, clinical features,
      treatments and outcome in a group of 68 hospitalized patients (adults and
      children) with fungal isolates recovered from 103 urinary samples. Underlying
      medical conditions were present in most patients. In the pediatric group, urinary
      tract abnormalities (86%) and prematurity (19%)accounted for the majority of the
      cases. Diabetes mellitus (28%), nephrolithiasis, and benign prostatic hyperplasia
      were the most common diseases in adults. Indwelling urethral catheters were noted
      in 38% of the pediatric patients and in 43% of adults during hospitalization.
      Candida albicans strains were responsible for 97% and 75% of positive cultures in
      children and adults, respectively. Symptoms such as fever, dysuria, frequency and
      flank pain were generally absent in both groups. Fluconazole was the most
      frequent antifungal utilized (61%) in children and ketoconazole in the adult
      group (42%). Removing the urinary catheter was attempted in 6 pediatric patients
      (29%) and in only 8 adults (17%). One patient (4%) in the pediatric group died
      compared to 10 in the adult group (21%, p=0.04). Successful diagnosis and
      treatment of funguria depends on a clear understanding of the risk factors and
      awareness of fungal epidemiology.

PMID- 11980595
TI  - Effectiveness of a mass immunization campaign against serogroup C meningococci in
      children in the federal state of Santa Catarina, Brazil.
AB  - In addition to vaccine efficacy studies, there is a pressing need to evaluate
      vaccine effectiveness in a way that takes into account the limitations of health
      care systems in certain settings. An attempt to reach this objective was
      exemplified by a vaccination campaign against serogroup C meningococci in the
      federal state of Santa Catarina, in Brazil. A polysaccharide vaccine against
      serogroup C meningococci was administered to all individuals between 6 months and
      14 years of age in March, 1996, in the municipalities that had the highest
      incidence of meningococcal disease in the previous year. All cases of the disease
      due to this serogroup observed in Santa Catarina during a 1-year period before
      and after the vaccination were included in the analysis. The cumulative incidence
      rate ratio was calculated for the unvaccinated compared to the vaccinated area.
      As a second step, the ratio of this quantity for the period before and after the
      vaccination, i.e. the ratio of the rate ratios (RRR), was calculated. One minus
      RRR was used to estimate the vaccine effectiveness. In the general population,
      the vaccine effectiveness was 74.3% (95% confidence intervals 52.7% to 99.6%). In
      children 6 months to 14 years, vaccine effectiveness was 93.1% (85.2% to 100%).
      Vaccine effectiveness could not be confirmed within more specific age bands,
      probably due to the lack of statistical power. It is concluded that group C
      meningococcal vaccine is effective in reducing the occurrence of meningococcal
      disease in children 6 months to 14 years of age, and that the ratio of rate
      ratios (RRR) in a useful method to evaluate vaccine effectiveness.

PMID- 11980596
TI  - Hyperlipidemia related to the use of HIV-protease inhibitors: natural history and
      results of treatment with fenofibrate.
AB  - Hyperlipidemia has been frequently recorded as a side effect of treating HIV
      patients with protease inhibitors (PI). This study was initiated to analyze the
      modifications on blood lipids in HIV-patients receiving PI and the safety and
      efficacy of the treatment with fenofibrate. Total (TC) and HDL-cholesterol,
      triglycerides (TG), and CD(4)(+) T-cell counts were measured in 30 HAART-naive
      patients (Group I) before and after PI introduction. In a second phase of the
      study, the effects of fenofibrate on lipids, CPK, CD(4)(+), and viral load were
      determined in 13 patients (Group II) with elevated TC or TG. In Group I, 60% of
      the patients showed TC or TG elevations. Average increments of 31% and 146% in TC
      and TG respectively (p<0.0006 and p<0.0001) were observed. In Group II,
      fenofibrate treatment was associated with decrements of 6.6% (TC) and 45.7% (TG)
      (p=0.07 and 0.0002) and no modifications on CPK, CD(4)(+), and viral load. In
      conclusion, hyperlipidemia is common during the treatment of HIV with protease
      inhibitors, and fenofibrate appears to be an effective and safe choice for its
      treatment.

PMID- 11980597
TI  - Antibiotic resistance and molecular typing of Pseudomonas aeruginosa: focus on
      imipenem.
AB  - Susceptibility tests by disk diffusion and by E-test and molecular typing by
      macrorestriction analysis were performed to determine the relatedness of
      Pseudomonas aeruginosa isolates from three distinct hospitals. The resistance
      profile of 124 isolates to 8 antimicrobial agents was determined in three
      different hospitals, in Porto Alegre, Brazil. Frequencies of susceptibility
      ranged from 43.9% for carbenicillin to 87.7% for ceftazidime. Cross-resistance
      data of imipenem-resistant isolates indicated that most (70%) were also resistant
      to carbenicillin, although 30% remained susceptible to ceftazidime and cefepime.
      In general, susceptibility profiles were not able to determine relatedness among
      isolates of P. aeruginosa. On the other hand, molecular typing by
      macrorestriction analysis demonstrated high discriminatory power and identified
      66 strains among 72 isolates of P. aeruginosa. Imipenem-susceptible isolates were
      all different. However, identical clones of imipenem-resistant isolates were
      found in two of the hospitals, despite variable response to other antibiotics. No
      clustering of infection among the different medical centers was observed. In
      conclusion, clones of P. aeruginosa did not spread among the different hospitals
      in our city even though related isolates of imipenem-resistant P. aeruginosa were
      found.

PMID- 11980599
TI  - HIV prevalence among blood donors in a blood bank in Curitiba (Brazil).
AB  - There still is no cure for the acquired immunodeficiency syndrome (AIDS). Its
      etiologic agent is the human immunodeficiency virus (HIV), and transmission
      occurs through sexual relationships, contacts with blood, and vertically (mother
      to child). In this study, we sought to determine the prevalence of HIV among
      blood donors at a blood bank in Curitiba. We studied 213,666 blood donations made
      from March 1, 1992, to April 25, 1999. Each potential blood donor first answered
      a questionnaire, submitted to a clinical examination, and filled out a self
      exclusion card. Blood was collected and analyzed only from the candidates
      approved by the first two criteria. Two tests were used to detect HIV: ELISA for
      screening, and Western-Blot for confirmation. The results were analyzed
      statistically by determining the 95% confidence interval. Of the total number of
      donors, 156,942 were men, and 56,724 were women. There were 319 cases of HIV
      infection (244 men, 75 women). There were no significant differences between
      genders, or among the different age groups, or between first-donation and
      repeated-donation donors. There was a significant predominance of HIV infection
      among single individuals compared to married, widowed, and other individuals. The
      same occurred among married and divorced individuals compared to widowed
      subjects. The prevalence of HIV among blood donors was 0.149% (0.155% among men
      and 0.132% among women). The frequency of HIV was statistically identical among
      new blood donors and repeat donors. A large number of HIV-infected married women
      was also observed.

PMID- 11980598
TI  - Compliance to antiretroviral medication as reported by AIDS patients assisted at
      the University Hospital of the Federal University of Mato Grosso do Sul.
AB  - Compliance to antiretroviral medication is a problem for AIDS patients.
      Compliance can be influenced by the characteristics of the therapeutic program,
      by the health guidance professionals, by the patient, and by society in general.
      A group of 139 Brazilian AIDS patients from the Infectious-Parasitic Diseases day
      clinic at the University Hospital of the Federal University of Mato Grosso do Sul
      were interviewed from September 27, 1999 to January 21, 2000. We identified and
      evaluated the frequency of noncompliance to antiretroviral medication, as well as
      the associated motives. Those who ingested 80%, or more, of prescribed dosages
      during the week previous to the interview were considered compliant. Among the
      patients interviewed, 70% mentioned loss or misplacement of medicine, and 63%
      were considered compliant. Average compliance was 75.8%, with no difference
      between the sexes. The reasons given for non-compliance were: absent-mindedness
      or forgetfulness (67.7%), lack of medicine (41.9%), side effects (21.5%),
      complexity of prescribed regimens (12.9%), fatigue (9.7%), and voluntary
      interruption (7.5%). The non-compliance observed among these patients indicates
      that health service personnel should promote activities to recuperate these
      therapeutic programs, employing methodologies appropriate to the characteristics
      of this population.

PMID- 11980600
TI  - Childhood pneumonia: clinical aspects associated with hospitalization or death.
AB  - OBJECTIVE: To determine which available information at an Emergency Room (ER)
      consultation is associated with hospitalization or death among children with
      pneumonia. DESIGN: Prospective cohort study. SETTING: The ER of one university
      and one private hospital. MEASUREMENT: Using stepwise logistic regression we
      analyzed factors that showed a univariate association. MAIN RESULTS: Of 2,970
      cases, the median age was 1.83 years (range 2 days to 14.5 yrs, mean 2.76 +/-
      2.72 yrs); 25.8% were hospitalized and 0.8% died. Age (2-11 mos, OR 0.4 [0.2
      0.6]; 12-59 mos, OR 0.2 [0.1-0.4]; > or = 5 yrs, OR 0.1 [0.08-0.3]), malnutrition
      (OR 2.0 [1.4-2.7]), underlying chronic illness (OR 1.4 [1.1-1.8]), tachypnea (OR
      1.8 [1.4-2.4]), chest indrawing (OR 1.7 [1.4-2.2]), and somnolence (OR 1.8 [1.4
      2.4]) were associated with hospitalization and age (2-11 mos, OR 0.3 [0.08-0.8];
      > or = 12 mos, OR 0.06 [0.02-0.2]), malnutrition (OR 3.1 [1.2-7.7]) and
      underlying chronic illness (OR 4.3 [1.6-11.0]) were associated with death in the
      multivariate analysis. CONCLUSIONS: Several clinical aspects may be used in
      assessing need for hospitalization (i.e. young age, malnutrition, underlying
      chronic illness, tachypnea, chest indrawing and somnolence) for children with
      pneumonia seen at the ER. Individual intrinsic factors such as age, malnutrition
      and underlying chronic illness were independently associated with death.
      Pneumonia should be considered a treatable disease and complete recovery can be
      achieved in the majority of the cases.

PMID- 11980601
TI  - Evaluation of disease patterns, treatment and prognosis of tuberculosis in AIDS
      patient.
AB  - Patterns of disease, diagnosis, treatment and prognosis of tuberculosis in 100
      patients co-infected with AIDS at Casa da AIDS clinic was studied. Demographic
      characteristics were as follows: 76 male patients, 24 female patients, 67
      caucasian, average 35.8 years-old (SD +/- 8.5). Sexual transmission of HIV was
      reported in 68 patients. Pulmonary tuberculosis was seen in 40 patients,
      extrapulmonary in 11, and combined in 49 patients. In 63 patients, TCD(4)(+)
      counts were below 200/mm(3) when tuberculosis was diagnosed. Fifty-five patients
      had their diagnoses confirmed by bacteriological identification of Mycobacterium;
      either through direct observation and/or culture. Tuberculosis was treated with
      rifampin, isoniazid and pyrazinamide in 60 patients, reinforced treatment in 14
      and alternative treatment in the other 13 patients. Tuberculosis therapy lasted
      up to 9 months in 66% of the patients. Fifty-four patients were treated with a
      two-drug antiretroviral regimen and the remaining 46 patients received a triple
      regimen, which included a protease inhibitor. Among the latter, 35 patients were
      co-treated with rifampin. The occurrence of hepatic liver enzyme abnormalities
      was statistically related to alternative antiretroviral regimens (p = 0.01) and
      to the co-administration of rifampin and protease inhibitor (p = 0.019). Clinical
      resolution of tuberculosis was obtained in 74 patients. Twelve patients died
      during tuberculosis treatment. Resolution of tuberculosis was statistically
      significant related to antituberculosis treatment adherence (p = 0.001). The risk
      of no response to the treatment was 1.84 times more frequent among patients
      treated with alternative regimens regardless of the duration of the therapy. We
      conclude that the characteristics of tuberculosis in HIV infected patients
      requires that special attention be directed to the types and duration of both
      antiretroviral and anti-TB therapy in order to achieve the highest level of care.

PMID- 11980602
TI  - Reiter's syndrome associated with the Acquired Immunodeficiency Syndrome: a case
      report.
AB  - The association of Reiter's Syndrome (RS) with the Acquired Immunodeficiency
      Syndrome (AIDS) is seldom mentioned in the medical literature. This report
      illustrates this relationship in a 46 years old male patient suffering from AIDS
      (CD(4)(+) = 240 cells/mm(3), CD(8)(+) = 1,301 cells/mm(3) and viral load =
      330,000 copies/ml), pulmonary tuberculosis (positive catarrhal bacilluscopy), and
      RS. The diagnosis of RS was based on the combination of dermatological and
      articular alterations. The patient s cutaneous lesions were characterized by
      exfoliation and the formation of crusts located on the face, scalp, genitals,
      hands, and feet; onychodystrophy with opacity; yellowish coloring; and
      hyperkeratosis of the nails. Articular lesions led to progressive deformity of
      phalangeal joints of the hands, and intensive arthralgia, mainly of the larger
      joints (shoulders, elbows, hips and knees). AIDS treatment was administered with
      anti-retroviral drugs (zidovudine and didanosine); for tuberculosis (isoniazid,
      rifampicine, and pyrazinamide); and (prednisone and inometacine) for the RS. The
      patient recovered with the improvement of articular symptoms; however, on the
      eighth day of treatment, the patient showed significant hemoptysis and
      hypovolemic shock, and died. The association of RS and HIV infection is reviewed.

PMID- 11980603
TI  - Concomitant prostatic schistosomiasis and adenocarcinoma: case report and review.
AB  - The term schistosomiasis encompasses a group of infectious disorders caused by
      five species of the genus Schistosoma, a blood trematode of outstanding
      importance in tropical areas. Some of these disorders have long been associated
      with malignant neoplasia, the most striking association being between disease
      caused by Schistosoma haematobium, the predominant etiological agent of urinary
      schistosomiasis, and squamous cell carcinoma of the bladder, a relatively
      uncommon vesical cancer in non-endemic areas. Four cases of simultaneous
      adenocarcinoma and schistosomiasis of the prostate have been previously reported
      (S. haematobium in three and S. mansoni in one). We report a fifth case of
      concomitant adenocarcinoma and schistosomiasis of the prostate in a 68-year-old
      Brazilian patient infected with S. mansoni. We also review the medical literature
      on the association between schistosomiasis and cancer.

PMID- 11980604
TI  - Bilateral peripheral facial palsy secondary to lymphoma in a patient with
      HIV/AIDS: a case report and literature review.
AB  - Neurological complications represent one of the most important causes of
      morbidity and mortality in patients with HIV/AIDS. However, peripheral neuropathy
      comprises only 5% to 20% of the total neurological complications and facial nerve
      palsy, especially when it is bilateral, is a less common manifestation.
      Peripheral facial palsy has been considered as a possible neurological
      complication of the early stage of HIV infection but the number of reported cases
      in the literature is limited. Histological findings of nervous tissue in
      peripheral facial palsy at an early stage of HIV infection include a degenerative
      and not suppurative inflammatory process, but its etiology remains obscure.
      Peripheral facial palsy in the late stage of HIV infection is characterized by an
      advanced immunological deficit and generally it is secondary to an opportunistic
      infection of the CNS, such as neurotoxoplasmosis and lymphoma. However, this
      peripheral attack of the facial nerve is not very common at this late stage of
      HIV infection. Bilateral peripheral facial palsy as a complication of non-Hodgkin
      s lymphoma is considered an extremely rare entity. There are no published reports
      of bilateral peripheral facial palsy secondary to lymphomas or other neoplasms of
      the CNS in immunosuppressed patients. Non-Hodgkin s lymphoma (NHL) has been
      considered a late and relatively common manifestation of HIV infection, but an
      exact cause for the higher incidence of this malignant neoplasm in HIV/AIDS
      patients is still uncertain.

PMID- 11980606
TI  - Noncompliance with tuberculosis treatment by patients at a tuberculosis and AIDS
      reference hospital in midwestern Brazil.
AB  - INTRODUCTION: In developing countries, there is little information about the risk
      factors that predict noncompliance with tuberculosis (TB) treatment in hospitals.
      OBJECTIVE: This study analyzes possible factors associated with noncompliance
      with TB treatment among patients treated at HAA. DESIGN: A retrospective cohort
      study was made including all patients who initiated TB treatment at HAA, from
      January to December 1998. A standard form was used to review medical records and
      to collect data on each patient. This data was evaluated in comparison with data
      from the state TB control program. RESULTS: Of the 341 patients included in the
      study, 186 (61.2%) were considered cured and 67 (22%) were non-compliant. The
      factors associated with noncompliance were: previous anti-TB treatment (RR =
      1.95, 95% CI 1.29 to 2.93), prescription of drugs other than the standard first
      line regimen proposed by the Brazilian Health Ministry (Rifampin + Isoniazide +
      Pyrazinamide) (RR = 0.54, 95% CI 0.35 to 0.83), the need for hospitalization (RR
      = 2.19, 95% CI 1.46 to 3.29) and non-inclusion in the hospital s TB Control
      Program for treatment follow up (RR = 0.54, 95% CI 0.35 to 0.82). SETTING: Anuar
      Auad Hospital (HAA) Goiania, Goias, Brazil. CONCLUSION: Our results indicate the
      importance of establishing Tuberculosis Control Programs in hospitals, while
      paying special attention to patients with risk factors for noncompliance with TB
      treatment.

PMID- 11980605
TI  - A survey of the incidence of neonatal sepsis by group B Streptococcus during a
      decade in a Brazilian maternity hospital.
AB  - Group B Streptococcus (GBS) is the main etiological agent of neonatal sepsis in
      developed countries, however there is no detailed information on its incidence in
      Brazil. We registered the incidence and lethality of GBS infection in a Brazilian
      private maternity hospital from April 1991 to March 2000. Maternal risk factors
      contributing to neonatal infections were also scored. The rate of infection was
      determined by checking for GBS in the blood and liquor of symptomatic neonates
      within 72 hours of birth. Sepsis and/or early onset meningitis were diagnosed in
      43 neonates (32 cases in blood, 1in liquor and 10 in blood and liquor). The
      overall incidence was 0.39 per thousand neonates and remained quite constant
      throughout the period, ranging from 0.25-0.63. Septic shock occurred in 33
      neonates within 1 to 36 hours of birth (mean 15 hours). Among those patients, 26
      (60%) died between the 5th and the 85th hour after birth. Maternal risk factors,
      according to CDC criteria, included: gestational age below 37 weeks in 26 cases
      (60%), amniorrhexis equal or superior to 18 hours in 7 cases (16%), and maternal
      temperature equal or superior to 38(o)C in 4 cases (9%). None of the mothers had
      received prophylactic antibiotics during labor nor were urine, rectal or vaginal
      swabs screened for GBS. Although the incidence of GBS infection in the population
      in this study was lower than that found in developed countries, its rate of
      mortality was higher. The death rate could be reduced through recognition of the
      risk factors and prophylactic antibiotics during labor.

PMID- 11980608
TI  - Antimicrobial therapy for community-acquired pneumonia in adults.
AB  - This is part of the series of practice guidelines commissioned by the Brazilian
      Society for Infectious Diseases through its Practice Guidelines Committee. The
      purpose of these guidelines is to provide assistance to clinicians in the
      antimicrobial treatment of community-acquired pneumonia (CAP) in immunocompetent
      adults. Panel members and consultants are experts in adult infectious diseases.
      The guidelines are evidence based where possible. The recommendations included in
      this document were elaborated based on the most frequently isolated pathogens and
      their antimicrobial susceptibilities. The etiology was based mainly on
      international studies, since there are very few regional data. On the other hand,
      the antimicrobial susceptibilities of main bacterial causes of CAP were based on
      the results of several antimicrobial resistance surveillance studies recently
      performed in Brazil. Other reference guidelines for the treatment of CAP, such as
      those elaborated by the Infectious Diseases Society of America and by the
      Canadian Infectious Diseases Society, were also discussed by the group during the
      elaboration of this document.

PMID- 11980607
TI  - Hepatitis C: a critical analysis of therapeutic response predictors.
AB  - Treatment of chronic hepatitis C is still unspecific. However, there is great
      expectancy concerning the new pegylated interferons. As there has been much
      controversy about the best parameters to determine whether treatment is
      effective, we analyzed several criteria currently used for evaluation, including
      serum alanine aminotransferase (ALT) normalization, viral load reduction and
      improvement of hepatic histology.

PMID- 11980609
TI  - Isolation of Salmonella enterica serotype Worthington from a splenic abscess in a
      patient with chronic myeloid leukemia.
AB  - Splenic abscesses are caused by Staphylococcus aureus, Streptococcus and bacteria
      belonging to the family Enterobacteriaceae. We report a case of splenic abscess
      caused by an unusual serotype of Salmonella. A 55 year old man was admitted with
      complaints of fever and abdominal pain. On the basis of clinical findings and
      laboratory reports, a diagnosis of chronic myeloid leukemia was made.
      Ultrasonography of the abdomen revealed a single large cystic lesion in the
      spleen. Percutaneous drainage of the abscess was carried out. Salmonella enterica
      serotype Worthington was isolated from a pus sample taken from the abscess. The
      isolate was resistant to ampicillin, gentamicin, cefotaxime, chloramphenicol and
      tetracycline, and sensitive to amikacin and norfloxacin. Serotype Worthington is
      an emerging pathogen. This is the first report of isolation of this serotype from
      a splenic abscess. In seriously ill patients, such infections should be treated
      with a combination of antibiotics to circumvent problems with multidrug
      resistance.

PMID- 11980610
TI  - Atypical fulminant Rickettsia rickettsii infection (Brazilian spotted fever)
      presenting as septic shock and adult respiratory distress syndrome.
AB  - Brazilian spotted fever, caused by Rickettsia rickettsii, has been increasingly
      reported in Brazil especially in the southeastern states. The severe and
      fulminant forms of the disease are not unusual but most of the reported fatal
      cases have shown some typical clinical clue, which leads the attending physician
      to a correct diagnosis. We report a probable case of atypical fulminant Brazilian
      spotted fever that presented full-blown septic shock associated with Adult
      Respiratory Distress Syndrome (ARDS) and delayed uncharacteristic rash with an
      over four-fold increase in reciprocal IgM, but not IgG titer against Rickettsia
      rickettsii. Brazilian practitioners should be aware of the possibility of
      Brazilian spotted fever as a cause of fulminant primary sepsis with ARDS;
      improved laboratory methods are necessary for the rapid diagnosis of such cases.

PMID- 11980613
TI  - The role of 11beta-hydroxysteroid dehydrogenase activity in the metabolic
      syndrome: lessons learned from the animal model.

PMID- 11980611
TI  - Salpingitis due to Entamoeba histolytica.
AB  - We describe the pathology of a unique case of Fallopian tube amebiasis,
      associated with hydrosalpinx, in a 21-year-old woman. She complained of lower
      abdominal pain, had a foul-smelling green vaginal discharge and fever during one
      week. There was a discrete increase in body temperature and a painful abdominal
      palpation at the lower right side, with signs of local peritoneal irritation.
      Pathological examination showed a marked dilatation of the fallopian tube and
      hydrosalpinx. Microscopic examination showed a poorly formed granuloma composed
      of large macrophages with many Entamoeba histolytica trophozoites inside the
      fallopian tube. Even though it is a rare disease the correct diagnosis of female
      genital tract amebiasis is of great importance for the indication of proper
      therapy.

PMID- 11980614
TI  - Increased adipose tissue secretion of interleukin-6, but not of leptin,
      plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves'
      hyperthyroidism.
AB  - OBJECTIVE: This study was designed to investigate adipose tissue secretion of
      interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-alpha) and
      plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism. DESIGN: We
      studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for
      Graves' hyperthyroidism and 16 healthy, euthyroid control subjects. METHODS:
      Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF
      alpha and PAI-1 were analysed. Subcutaneous fat biopsies were taken for
      subsequent measurement of IL-6, leptin, TNF-alpha and PAI-1 protein secretion.
      RESULTS: In patients with Graves' disease, the anti-thyroid treatment resulted in
      significant reductions of plasma thyroxine and triiodothyronine levels. No
      differences in serum concentration or adipose tissue secretion of leptin or TNF
      alpha were observed either before, as compared with during, anti-thyroid
      treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1
      activity, but not adipose tissue secretion of PAI-1, was increased both in
      Graves' disease before as compared with during anti-thyroid treatment (P=0.01)
      and in thyrotoxic patients compared with euthyroid controls (P=0.0001). Finally,
      adipose secretion of IL-6 was increased both before (8-fold, P=0.001) and during
      (6-fold, P<0.0001) treatment as compared with control subjects. Accordingly,
      serum concentration of IL-6 was also increased by about 50% in thyrotoxic
      patients as compared with healthy controls (P=0.03). CONCLUSIONS: In Graves'
      hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6,
      but not of leptin, TNF-alpha or PAI-1, is markedly increased in comparison with
      euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate
      adipose tissue release of IL-6.

PMID- 11980615
TI  - Epidemiological survey on the relationship between different iodine intakes and
      the prevalence of hyperthyroidism.
AB  - OBJECTIVE: To investigate the effect of different levels of iodine intake on the
      prevalence of hyperthyroidism and the impact of universal salt iodization on the
      incidence of hyperthyroidism. DESIGN: A comparative cross-sectional and
      longitudinal survey was conducted in three areas with borderline iodine
      deficiency, mild iodine excess (previously mild iodine deficiency) and severe
      iodine excess. Universal salt iodization had been introduced 3 years previously
      except in the area with borderline iodine deficiency. METHODS: In total 16 287
      inhabitants from three areas answered a questionnaire concerning the history of
      thyroid disease. Among them 3761 unselected subjects received further
      investigations including thyroid function, thyroid autoantibodies, thyroid
      ultrasonography and urinary iodine excretion. RESULTS: Among areas with median
      urinary iodine excretion of 103 microg/l, 375 microg/l and 615 microg/l (P<0.05),
      the prevalence of hyperthyroidism did not differ significantly (1.6%, 2% and
      1.2%). The prevalence of subclinical hyperthyroidism was higher in areas with
      borderline iodine deficiency and mild iodine excess than in the area with severe
      excess iodine intake (3.7%, 3.9% and 1.1%, P<0.001). The prevalence of Graves'
      disease and its proportion in hyperthyroidism did not differ among areas. The
      incidence of hyperthyroidism did not significantly increase after the
      introduction of universal salt iodization. CONCLUSION: Different iodine intakes
      under a certain range do not affect the prevalence and type of hyperthyroidism.
      Subclinical hyperthyroidism is more prevalent in the iodine deficient area than
      in the severe iodine excessive area. In the area with mild iodine deficiency, the
      introduction of universal salt iodization may not be accompanied by an increased
      incidence of hyperthyroidism.

PMID- 11980616
TI  - Genetic analysis of lithium-associated parathyroid tumors.
AB  - OBJECTIVE: The aim of this study was to determine the primary genetic events that
      may underlie the formation of parathyroid tumors in patients with lithium
      associated hyperparathyroidism (HPT). METHODS: Comparative genomic hybridization
      (CGH), loss of heterozygosity (LOH) and multiple endocrine neoplasia type 1 gene
      (MEN1) mutation analysis were used to analyze twelve parathyroid tumors from nine
      patients with lithium-associated HPT. For comparison, CGH was also carried out in
      a non-lithium-associated group of thirteen sporadic parathyroid tumors. RESULTS:
      A higher prevalence of multiglandular disease in the lithium-associated HPT
      patients compared with the idiopathic sporadic patients was observed (Fisher's
      exact test, P=0.02). CGH alterations were detected in four lithium-associated
      parathyroid tumors, involving loss at 1p, 11, 15q, 22q and gain of the X
      chromosome. In addition, one of these four cases exhibited LOH at 11q13 and was
      found to contain a novel somatic MEN1 mutation (c.1193insTAC). Although fewer
      lithium-associated parathyroid tumors were shown to contain genetic alterations
      compared with the sporadic parathyroid tumors, the changes detected were those
      frequently associated with both familial and sporadic parathyroid tumorigenesis.
      CONCLUSION: This is, to our knowledge, the first genetic analysis of parathyroid
      tumors in lithium-associated HPT patients. Our data indicated that the majority
      of lithium-associated parathyroid tumors do not contain gross chromosomal
      alterations and suggest that in most cases the tumorigenic pathway is independent
      of MEN1 and genes at 1p34.3-pter and 1q21-q32. It is possible that other discrete
      genetic alterations or epigenetic changes, not screened for in this study, could
      also be responsible for parathyroid tumorigenesis in lithium-associated HPT.

PMID- 11980617
TI  - TNF-alpha gene polymorphism and plasma TNF-alpha levels are related to lumbar
      spine bone area in healthy female Caucasian adolescents.
AB  - OBJECTIVE: The cytokine tumor necrosis factor alpha (TNF-alpha) is an important
      regulator of bone metabolism. Polymorphisms in the promoter region of the TNF
      alpha gene at positions -308 and -863 have been identified. We investigated
      whether these polymorphisms and circulating TNF-alpha levels were related to bone
      mineral density and bone area in adolescent girls. DESIGN: Bone mineral density
      (BMD), bone area (BA), anthropometric characteristics and biochemical analyses
      were measured in adolescent girls and compared with regard to TNF-alpha genotype.
      METHODS: Allelic variants of the TNF-alpha gene in 97 girls, aged 16.9+/-1.2
      years (mean+/-S.D.), were identified using polymerase chain reaction and the
      restriction endonucleases NcoI and TaiI. Bone mineral density and bone area of
      the femoral neck, lumbar spine and total body were measured using dual energy X
      ray absorptiometry. RESULTS: Carriers of the rare -863 A allele (n=25) had higher
      body weight (P=0.03), lumbar spine BMD (P=0.02), and larger total BA (P=0.03),
      femoral neck area (P<0.05), and lumbar spine area (P=0.01). The independent
      predictors of BMD and BA were investigated using multiple regression. The TNF
      alpha-863 genotypes (beta=0.18, P=0.03) and the TNF-alpha plasma levels
      (beta=0.19, P=0.04) independently predicted BA of the lumbar spine but not BA or
      BMD of any other measured sites. No statistically significant differences in body
      constitution parameters, biochemical parameters, bone density, or bone area at
      the measured skeletal sites were found when comparing the groups defined by the
      allelic variants at position -308 (P=0.17-0.84). CONCLUSIONS: We found the TNF
      alpha-863 polymorphism and the TNF-alpha plasma levels to be independent
      predictors of lumbar spine area in healthy Caucasian adolescent females.

PMID- 11980618
TI  - Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in
      postmenopausal women: relationship to plasma parathyroid hormone and calcium and
      phosphate metabolism.
AB  - OBJECTIVE: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D
      (1,25(OH)(2)D) have previously only been investigated in young individuals, and
      these studies have failed to demonstrate a diurnal rhythm. We have studied
      whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in
      a diurnal rhythm in postmenopausal women. METHODS: Blood and urine were sampled
      with 2- and 4-h intervals in order to assess diurnal variations in plasma levels
      of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels
      and urinary excretion rates of calcium and phosphate. Additionally, the free
      1,25(OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP).
      RESULTS: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in
      the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during
      the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern
      of variation was found in plasma levels of DBP with peak levels 15% above nadir
      levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm.
      PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a
      diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the
      rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01).
      Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36,
      P=0.02). CONCLUSIONS: With the disclosure of a diurnal rhythm of total plasma
      1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have
      now been shown to exhibit diurnal variations. In clinical studies, the diurnal
      variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must
      be standardised according to the time of day.

PMID- 11980619
TI  - Relationship between serum parathyroid hormone, serum calcium and arterial blood
      pressure in patients with primary hyperparathyroidism: results of a multivariate
      analysis.
AB  - OBJECTIVE: To evaluate the possible relationship between serum calcium, serum
      parathyroid hormone (PTH) levels and arterial blood pressure (BP) in patients
      with primary hyperparathyroidism (HPT). DESIGN: A retrospective population-based
      study. METHODS: Charts of 194 patients with proven primary HPT were reviewed, and
      the main clinical and biochemical parameters were recorded. There were 48 men
      (24.7%) and 146 women (75.3%), with a median age of 59 years (range 23-82 years).
      Patients who used antihypertensive drugs or hormone replacement therapy had been
      previously excluded. All patients underwent successful parathyroidectomy, and
      were cured of their disease. RESULTS: There were no differences (P=NS) between
      men and women in systolic (143.3+/-19.1 vs 145.4+/-17.1 mmHg) and diastolic
      (87.1+/-12.3 vs 88.4+/-9.9 mmHg) BP, and in the main biochemical parameters. A
      significant (P<0.01) correlation was found between (i) serum calcium and serum
      PTH levels (r=0.39, F=88.36), (ii) age and BP, both systolic (r=0.61, F=118.16)
      and diastolic (r=0.48, F=64.5), and (iii) body mass index (BMI) and BP (r=0.45
      and 0.36 respectively). There was no significant association of serum calcium
      levels with systolic (r=0.0974, t=1.3422, P=0.18) or diastolic (r=0.1117,
      t=1.5409, P=0.12) BP, and of serum PTH levels with systolic (r=-0.0349, t=
      0.4783, P=0.63) or diastolic (r=-0.0793, t=-1.0913, P=0.28) BP. Multivariate
      analysis confirmed that none of the independent biochemical parameters
      significantly correlated with BP, both systolic and diastolic. CONCLUSIONS: In
      patients with primary HPT there is no relationship between PTH, calcium and BP.
      Thus, in hyperparathyroid patients, BP should be considered as an independent
      variable, mainly related to age and BMI.

PMID- 11980620
TI  - Clinical and molecular analysis of three families with autosomal dominant
      neurohypophyseal diabetes insipidus associated with a novel and recurrent
      mutations in the vasopressin-neurophysin II gene.
AB  - OBJECTIVE: To test further the hypothesis that autosomal dominant
      neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations
      in the vasopressin-neurophysin II (AVP-NPII) gene that exert a dominant negative
      effect by producing a precursor that misfolds, accumulates and eventually
      destroys the neurosecretory neurons. METHODS: Antidiuretic function, magnetic
      resonance imaging (MRI) of the posterior pituitary and AVP-NPII gene analysis
      were performed in 10 affected members of three unreported families with adFNDI.
      RESULTS: As in previously studied patients, adFNDI apparently manifested after
      birth, was due to a partial or severe deficiency of AVP, and was associated with
      absence or diminution of the hyperintense MRI signal normally emitted by the
      posterior pituitary, and with a heterozygous mutation in the AVP-NPII gene. In
      family A, a transition 275G-->A, which predicts replacement of cysteine 92 by
      tyrosine (C92Y), was found in the index patient, but not in either parent,
      indicating that it arose de novo. The six affected members of family B had a
      transversion 160G-->C, which predicts replacement of glycine 54 by arginine
      (G54R). It appeared de novo in the oldest affected member, and was transmitted in
      a dominant manner. In family C, six of 15 living affected members were tested and
      all had a novel transition, 313T-->C, which predicts replacement of cysteine 105
      by arginine (C105R). It, too, was transmitted in a dominant manner. As in other
      patients with adFNDI, the amino acids replaced by the mutations in these three
      families are known to be particularly important for correct and efficient folding
      of the precursor. CONCLUSIONS: These findings are consistent with the
      malfolding/toxicity hypothesis underlying the pathogenesis of adFNDI. Moreover,
      they illustrate the value of genetic analysis in all patients who develop
      idiopathic diabetes insipidus in childhood, even if no other family members are
      affected.

PMID- 11980621
TI  - IGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly
      patients with inflammation receiving refeeding therapy.
AB  - OBJECTIVE: To investigate the mechanisms determining the success or failure of
      refeeding therapy in malnourished elderly patients with inflammation by studying
      changes in plasma IGF-I, GH-binding protein (GHBP) and IGF-binding protein
      (IGFBP) levels and IGFBP-3 proteolysis. DESIGN AND METHODS: We studied 15
      severely malnourished hospitalized elderly patients. Weight, food intake, plasma
      albumin, transthyretin, C-reactive protein (CRP), orosomucoid, interleukin-6 (IL
      6), IGF-I, intact and proteolytically degraded IGFBP-3 and GHBP levels were
      determined on admission and during refeeding therapy designed to increase food
      intake to 40 kcal/kg body weight per day (15% protein). RESULTS: Plasma IGF-I,
      IGFBP-3 and GHBP levels were significantly low for age on admission in all
      malnourished elderly patients. They increased in nine patients as nutritional
      status improved (albuminemia >30 g/l; transthyretinemia >200 mg/l or weight gain
      >5% of initial body weight) and levels of inflammation markers decreased (group
      1). In contrast, plasma IGF-I, IGFBP-3 and GHBP levels remained low in six
      patients in whom nutritional status failed to improve and levels of inflammation
      markers increased (group 2). IGF-I showed greater variations than IGFBP-3 or GHBP
      with respect to nutritional status. High plasma CRP and IL-6 levels were
      associated with high levels of IGFBP-3 proteolysis. CONCLUSION: Efficient
      refeeding therapy was associated with a significant increase in IGF-I plasma
      levels. In patients with severe and persistent inflammation, high levels of
      proteolysis of IGFBP-3 may have contributed to the low plasma IGF-I levels,
      persistence of hypercatabolism and lack of improvement in nutritional status.

PMID- 11980622
TI  - Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or
      in combination with GHRH: comparison with the insulin tolerance test.
AB  - OBJECTIVE: The diagnosis of GH deficiency in adults should be made using
      provocative testing of GH secretion. The insulin tolerance test (ITT) is
      recommended as the gold standard investigation. Because of the risk of serious
      complications, patients with epilepsy or known ischemic heart disease should not
      undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding
      to specific hypothalamic and pituitary receptors. We assessed the diagnostic
      capability of GH stimulation by GHRP-6 alone or in combination with GHRH in
      comparison to the results of an ITT. DESIGN: Twenty patients underwent an ITT for
      suspected pituitary or adrenal disease. Either GHRP-6 (1 microg/kg) alone, or
      GHRP-6 in combination with GHRH (1 microg/kg) were administered on different
      days. Blood samples were obtained during a subsequent 90-min period for
      measurement of GH. RESULTS: Ten patients had a GH peak response of less than 3
      microg/l during ITT and were considered growth hormone deficient (GHD). The GH
      mean peak (+/-S.E.M., range) in this group was 0.7 microg/l (+/-0.3, 0.1-2.9)
      compared with 14.5 microg/l (+/-3.5, 3.8-40.8) in the group of patients with a GH
      peak response of more than 3 microg/l (growth hormone sufficient (GS)). For the
      GHRP-6 test, the GH mean peak was 1.3 microg/l (+/-0.6, 0.1-6.7) in the GHD group
      versus 25.7 microg/l (+/-5.5, 7.7-54.2) in the GS group. After GHRP-6+GHRH, the
      GH mean peaks were 4.0 microg/l (+/-1.3, 0.2-11.9) versus 54.7 microg/l (+/-11.1,
      13.9-136.0) respectively. During administration of GHRP-6, the only side effects
      observed were flush symptoms. CONCLUSIONS: Peak GH levels below 7 microg/l for
      the GHRP-6 test and below 13 microg/l for the combined GHRP-6+GHRH test
      identified all patients with GH deficiency correctly as defined by ITT. The
      results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and
      specific as an ITT for the diagnosis of adult GH deficiency.

PMID- 11980623
TI  - Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin
      suppressed normal men.
AB  - OBJECTIVE: In a phase I single-centre, open, randomized study, the
      pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5%
      testosterone were evaluated in 26 healthy male volunteers. DESIGN: To eliminate
      the influence of endogenous serum testosterone, gonadotrophins and endogenous
      testosterone secretion were suppressed by a single intramuscular injection of 400
      mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g
      testosterone gel daily for 10 days. Half the men in each group washed the gel off
      10 min after it had been applied. RESULTS: In all the men, a marked suppression
      of LH, FSH, testosterone, dihydrotestosterone (DHT) and oestradiol was observed
      after norethisterone treatment. Physiological serum concentrations of
      testosterone were restored during the 10-day treatment period in the group of men
      applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone
      from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not
      exceed normal values. Washing 10 min after gel application did not influence the
      resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to
      achieve physiological serum concentrations of testosterone. CONCLUSION:
      Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is
      able to achieve constant physiological testosterone concentrations in
      gonadotrophin-suppressed men. Washing the skin after 10 min does not influence
      the pharmacokinetic profile and thus significantly reduces the risk of
      contamination of female partners or infants.

PMID- 11980624
TI  - Short boys treated with growth hormone show normal progression of testicular size
      and achieve normal serum testosterone concentrations.
AB  - OBJECTIVE: To determine whether there is evidence for impaired testicular
      function at final height in short boys treated with growth hormone (GH) during
      their childhood and adolescence. STUDY DESIGN: The analysis was restricted to
      males who had isolated GH deficiency or idiopathic short stature, and who were
      included in the Swedish National Registry and the Swedish GH trials. The subjects
      had to have been treated with GH for at least 4 years; the treatment had to have
      been started prepubertally, given for at least one year before the onset of
      puberty and the subjects had to have reached final height. One hundred and eleven
      boys fulfilled the criteria. METHODS: Testicular volumes were determined by
      orchidometer in each boy when GH treatment was started and at final height.
      Samples for testosterone measurements were collected from 77 boys at final
      height, and were measured by RIA. RESULTS: Each subject had normal testicular
      size (15 ml or more) and for those in whom concentrations were determined, serum
      testosterone levels and diurnal rhythm were normal. CONCLUSIONS: The results of
      our survey do not show evidence of testicular impairment following GH therapy.

PMID- 11980625
TI  - Nitric oxide modulation of renal and cardiac hemodynamics in type 2 diabetes.
AB  - OBJECTIVE: To evaluate endothelial function in type 2 diabetic patients with and
      without diabetic nephropathy. METHODS: We studied the effects of systemic
      infusion of the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine (L
      NMMA) on cardiovascular and renal hemodynamics in six type 2 diabetic patients
      with microalbuminuria (D2-MA), six type 2 diabetic patients with normoalbuminuria
      (D2-NA) and five control subjects. Both type 2 diabetic patients and control
      subjects had mild arterial hypertension. RESULTS: L-NMMA infusion decreased the
      cardiac index in all groups. A reduction in glomerular filtration rate (GFR) and
      an increase in filtration fraction were observed only in controls. Renal plasma
      flow decreased in controls and D2-NA patients and renal vascular resistance
      increased in all groups. CONCLUSIONS: The effect of L-NMMA on cardiac output was
      similar in controls and type 2 diabetic patients with and without diabetic
      nephropathy. In contrast, the effect on GFR was impaired in both diabetic groups,
      suggesting that glomerular NO homeostasis is altered in type 2 diabetes. Moreover
      the discrepancy, in diabetic patients, between cardiac and renal effects during L
      NMMA infusion suggests that the modulation of glomerular hemodynamics is
      independent from NO-regulated cardiac output.

PMID- 11980626
TI  - Homozygous combination of calpain 10 gene haplotypes is associated with type 2
      diabetes mellitus in a Polish population.
AB  - OBJECTIVE: The polymorphisms of two genes have recently been associated with
      complex forms of type 2 diabetes mellitus (T2DM): calpain 10 and peroxisome
      proliferator-activated receptor-gamma (PPARgamma). Calpain 10 is a member of a
      large family of intracellular proteases. It was shown in Mexican-Americans and
      other populations that variants of three single nucleotide polymorphisms (SNPs), 
      43, -19, and -63, of this ubiquitously expressed protein influence susceptibility
      to T2DM. However, substantial differences were shown between ethnic groups in at
      risk alleles and haplotypes as well as in their attributable risk. Thus, it is
      important to determine the role of calpain 10 in various populations. AIM: To
      examine the role of calpain 10 SNPs -43, -19, and -63 in genetic susceptibility
      to T2DM in a Polish population. METHODS: Overall, 377 individuals were examined:
      229 T2DM patients and 148 control individuals. The groups were genotyped for
      calpain 10 SNP-43, SNP-19, and SNP-63. SNP-19 was examined by electrophoresis of
      the PCR product on agarose gel by size, while the restriction fragment length
      polymorphism (RFLP) method was used for the two other markers. Differences in
      allele, genotype, haplotype, and haplotype combination distribution between the
      groups were examined by chi(2) test. RESULTS: Distributions of alleles,
      genotypes, and haplotypes at three loci defined by examined SNPs were not
      significantly different between the groups. However, the homozygote combination
      of 121 haplotype was more prevalent in the T2DM group than in the controls (17.9%
      vs 10.1%, P=0.039). No difference was observed in the 112/121 haplotype
      distribution. This heterozygous haplotype combination was associated with
      increased risk of T2DM in several populations. CONCLUSION: The results of our
      study suggest the association of calpain 10 121/121 haplotype combination created
      by SNPs -43, -19, and -63 with T2DM in a Polish population. However, we were not
      able to confirm the previously described role of the heterozygous 112/121
      haplotype combination in susceptibility to T2DM.

PMID- 11980627
TI  - New somatostatin analogs: will they fulfil old promises?

PMID- 11980628
TI  - SOM230: a novel somatostatin peptidomimetic with broad somatotropin release
      inhibiting factor (SRIF) receptor binding and a unique antisecretory profile.
AB  - OBJECTIVE: The aim of the present study was to identify a small, metabolically
      stable somatotropin release inhibiting factor (SRIF) analog with a more universal
      binding profile similar to that of natural somatostatin, resulting in improved
      pharmacological properties and hence new therapeutic uses. DESIGN: A rational
      drug design approach was followed by synthesizing alanine-substituted SRIF-14
      analogs to determine the importance of single amino acids in SRIF-14 for SRIF
      receptor subtype binding. The incorporation of structural elements of SRIF-14 in
      a stable cyclohexapeptide template in the form of modified unnatural amino acids
      resulted in the identification of the novel cyclohexapeptide SOM230. RESULTS:
      SOM230 binds with high affinity to SRIF receptor subtypes sst1, sst2, sst3 and
      sst5 and displays a 30- to 40-fold higher affinity for sst1 and sst5 than
      Sandostatin (octreotide; SMS 201-995) or Somatuline (BIM 23014). In vitro, SOM230
      effectively inhibited the growth hormone releasing hormone (GHRH)-induced growth
      hormone (GH) release in primary cultures of rat pituitary cells with an IC(50) of
      0.4+/-0.1 nmol/l (n=5). In vivo, SOM230 also potently suppressed GH secretion in
      rats. The ED(50) values determined at 1 h and 6 h post injection of SOM230
      indicated its very long duration of action in vivo. This property was also
      reflected in pharmacokinetic studies comparing plasma levels of SMS 201-995 and
      SOM230 after subcutaneous application. Whereas SMS 201-995 had a terminal
      elimination half life of 2 h, this was markedly prolonged in SOM230-treated
      animals (t(1/2)=23 h). Furthermore, in rats SOM230 demonstrated a much higher
      efficacy in lowering plasma insulin-like growth factor-I (IGF-I) levels compared
      with SMS 201-995. The infusion of 10 microg/kg/h of SOM230 using subcutaneously
      implanted minipumps decreased plasma IGF-I levels far more effectively than SMS
      201-995. After 126 days of continuous infusion of SOM230 plasma IGF-I levels were
      decreased by 75% of placebo-treated control animals. For comparison SMS 201-995,
      when used under the same experimental conditions, resulted in only a 28%
      reduction of plasma IGF-I levels, indicating a much higher efficacy for SOM230 in
      this animal model. It is important to note that the inhibitory effect of SOM230
      was relatively selective for GH and IGF-I in that insulin and glucagon secretion
      was inhibited only at higher doses of SOM230. This lack of potent inhibition of
      insulin and glucagon release was also reflected in the lack of effect on plasma
      glucose levels. Even after high dose treatment over 126 days no obvious adverse
      side effects were noticed, including changes in plasma glucose levels.
      CONCLUSION: We have identified a novel short synthetic SRIF peptidomimetic, which
      exhibits high affinity binding to four of the five human SRIF receptor subtypes
      and has potent, long lasting inhibitory effects on GH and IGF-I release.
      Therefore SOM230 is a promising development candidate for effective GH and IGF-I
      inhibition and is currently under evaluation in phase 1 clinical trials.

PMID- 11980629
TI  - Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and
      preserves islet function in mice.
AB  - OBJECTIVES: Inhibitors of the glucagon-like peptide-1 (GLP-1)-degrading enzyme,
      dipeptidyl peptidase IV (DPPIV), are being explored in the treatment of diabetes.
      We examined the long-term influence of a selective, orally active inhibitor of
      DPPIV (NVP DPP728), in normal female C57BL/6J mice and such mice rendered glucose
      intolerant and insulin-resistant by feeding a high-fat diet. DESIGN: In mice fed
      a standard diet (11% fat) or a high-fat diet (58% fat), NVP DPP728 (0.12
      micromol/g body weight) was administered in the drinking water for an 8 week
      period. RESULTS: DPPIV inhibition reduced plasma DPPIV activity to 0.01+/-0.03
      mU/ml vs 3.26+/-0.19 mU/ml in controls (P<0.001). Glucose tolerance after gastric
      glucose gavage, as judged by the area under the curve for plasma glucose levels
      over the 120 min study period, was increased after 8 weeks by NVP DPP728 in mice
      fed normal diet (P=0.029) and in mice fed a high-fat diet (P=0.036). This was
      accompanied by increased plasma levels of insulin and intact GLP-1. Glucose
      stimulated insulin secretion from islets isolated from NVP DPP728-treated animals
      after 8 weeks of treatment was increased as compared with islets from control
      animals at 5.6, 8.3 and 11.1 mmol/l glucose both in mice fed normal diet and in
      mice fed a high-fat diet (both P<0.05). Islet insulin and glucagon
      immunocytochemistry revealed that NVP DPP728 did not affect the islet
      architecture. However, the expression of immunoreactive glucose transporter
      isoform-2 (GLUT-2) was increased by DPPIV inhibition, and in mice fed a high-fat
      diet, islet size was reduced after treatment with NVP DPP728 from 16.7+/-2.6 x
      10(3) microm(2) in controls to 7.6+/-1.0 x 10(3) microm(2) (P=0.0019).
      CONCLUSION: Long-term DPPIV inhibition improves glucose tolerance in both normal
      and glucose-intolerant mice through improved islet function as judged by
      increased GLUT-2 expression, increased insulin secretion and protection from
      increased islet size in insulin resistance.

PMID- 11980630
TI  - Effect of chronic thyroxine treatment on IGF-I, IGF-II and IGF-binding protein
      expression in mammary gland and liver during pregnancy and early lactation in
      rats.
AB  - OBJECTIVE: Hyperthyroidism in rats produces organ hypertrophy and increases in
      circulating IGF-I and IGF-binding protein (IGFBP)-3. Chronic treatment with
      thyroxine (T(4)) during pregnancy advances parturition, blocks lactation and
      changes several hormone receptors in mammary gland and liver. Since IGFs are
      implicated in mammary and liver growth and in differentiation, we studied the
      effects of hyperthyroidism, induced by daily injections of T(4) (0.25 mg/kg).
      DESIGN AND METHODS: Using quantitative RT-PCR and in situ hybridization, the gene
      expression of IGF-I, IGF-II and the IGFBPs was determined in mammary gland and
      liver of rats at estrus and days 7, 14 and 21 of pregnancy (G7, G14, G21), day 1
      postpartum (L1) and 3 days after removing the litter (L4). Circulating levels of
      IGF-I, tri-iodothyronine (T(3)), PRL and GH were measured. RESULTS: T(4)
      treatment (HT) increased circulating T(3) save on G21, did not change serum IGF
      I, increased PRL on G21 and decreased GH on L1. PRL decreased on L1 because of
      the absence of lactation. Hepatic IGF-I mRNA was low during pregnancy and
      increased on L4. HT advanced this increase to L1. In controls, liver IGFBP-3 mRNA
      levels decreased from G14 to G21, whereas IGFBP-4 showed an inverse pattern. HT
      lowered IGFBP-3 mRNA and increased IGFBP-4. Increases in mammary concentrations
      of IGF-I, IGFBP-3 and IGFBP-4 mRNAs were seen on G21. HT delayed these peaks to
      L1. Mammary IGF-II and IGFBP-2 mRNA levels were high on G7 and G14, and fell
      afterwards, with HT having no effects. IGFBP-5 mRNA decreased during pregnancy
      and increased on L1. HT increased IGFBP-5 levels in early pregnancy and on L1.
      IGF-I mRNA localized to connective and epithelial mammary tissue, while IGFBP-2
      and IGFBP-5 mRNA was only in epithelial cells. CONCLUSION: These results imply a
      role for IGF-I, IGFBP-3 and IGFBP-4 in terminal mammary development, while IGF-II
      and IGFBP-2 may be implicated in early growth. IGFBP-5 has been implicated in
      mammary apoptosis, and the HT-induced increase may play a role in the premature
      mammary involution of the HT rats.

PMID- 11980631
TI  - Mutations at coding repeat sequences in mismatch repair-deficient human cancers:
      toward a new concept of target genes for instability.
AB  - Because the discovery of a link between mismatch repair deficiency and sporadic
      or inherited human cancers characterized by microsatellite instability (MSI-H
      tumors), genes containing coding repeat sequences have been found to be mutated
      at these repeats in MSI-H tumors from different primary sites as reported in the
      present review. Accumulation of such alterations appears to be the main molecular
      mechanism by which MSI-H cells accumulate functional changes with putative
      oncogenic effects. These mutations occur in many genes at variable frequencies.
      They can affect genes with a putative role in human carcinogenesis involved in
      different or similar pathways and are thus thought to be inactivating or
      activating events selected for in these cancers in a recessive or dominant
      manner. However, because of the high level of instability characterizing these
      cancers, they are also likely to occur in genes without any expected role in MSI
      H carcinogenesis. In light of these recent data, the concept of target genes for
      instability and their possible role in MSI-H cancers is reconsidered here.

PMID- 11980632
TI  - Endogenous reactivation of the RARbeta2 tumor suppressor gene epigenetically
      silenced in breast cancer.
AB  - Loss of expression of retinoic acid receptor beta2 (RARbeta2), a potent tumor
      suppressor gene, is commonly observed during breast carcinogenesis. RARbeta2
      silencing can be traced to epigenetic chromatin changes affecting the RARbeta P2
      promoter. Here we show that retinoic acid therapy fails to induce RARbeta2 in
      primary breast tumors, which carry a methylated RARbeta P2 promoter. DNA
      methylation leads to repressive chromatin deacetylation at RARbeta P2. By
      inducing an appropriate level of histone reacetylation at RARbeta P2 we could
      reactivate endogenous RARbeta2 transcription from unmethylated as well as
      methylated RARbeta P2 in breast cancer cell lines and xenograft tumors, and
      obtain significant growth inhibition both in vitro and in vivo. This study may
      have translational implications for breast cancer and other cancers carrying an
      epigenetically silenced RARbeta P2 promoter.

PMID- 11980633
TI  - Regulation of microtubule stability and mitotic progression by survivin.
AB  - Survivin is a member of the inhibitor of apoptosis (IAP) gene family, which has
      been implicated in both preservation of cell viability and regulation of mitosis
      in cancer cells. Here, we show that HeLa cells microinjected with a polyclonal
      antibody to survivin exhibited delayed progression in prometaphase (31.5 +/- 6.9
      min) and metaphase (126.8 +/- 73.8 min), as compared with control injected cells
      (prometaphase, 21.5 +/- 3.3 min; metaphase, 18.9 +/- 4.5 min; P < 0.01). Cells
      injected with the antibody to survivin displayed short mitotic spindles severely
      depleted of microtubules and occasionally underwent apoptosis without exiting the
      mitotic block or thereafter. Forced expression of survivin in HeLa cells
      profoundly influenced microtubule dynamics with reduction of pole-to-pole
      distance at metaphase (8.57 +/- 0.21 microm versus 10.58 +/- 0.19 microm; P <
      0.0001) and stabilization of microtubules against nocodazole-induced
      depolymerization in vivo. These data demonstrate that survivin functions at cell
      division to control microtubule stability and assembly of a normal mitotic
      spindle. This pathway may facilitate checkpoint evasion and promote resistance to
      chemotherapy in cancer.

PMID- 11980634
TI  - Platelet-derived growth factor D: tumorigenicity in mice and dysregulated
      expression in human cancer.
AB  - Platelet-derived growth factor (PDGF) has been directly implicated in
      developmental and physiological processes, as well as in human cancer and other
      proliferative disorders. We have recently isolated and characterized a novel
      protease-activated member of the PDGF family, PDGF D. PDGF D has been shown to be
      proliferative for cells of mesenchymal origin, signaling through PDGF receptors.
      Comprehensive and systematic PDGF D transcript analysis revealed expression in
      many cell lines derived from ovarian, renal, and lung cancers, as well as from
      astrocytomas and medulloblastomas. beta PDGF receptor profiling further suggested
      autocrine signaling in several brain tumor cell lines. PDGF D transforming
      ability and tumor formation in SCID mice was further demonstrated. Exploiting a
      sensitive PDGF D sandwich ELISA using fully human monoclonal antibodies, PDGF D
      was detected at elevated levels in the sera of ovarian, renal, lung, and brain
      cancer patients. Immunohistochemical analysis confirmed PDGF D localization to
      ovarian and lung tumor tissues. Together, these data demonstrate that PDGF D
      plays a role in certain human cancers.

PMID- 11980635
TI  - Dietary genistein negates the inhibitory effect of tamoxifen on growth of
      estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice.
AB  - The use of dietary isoflavone supplements by postmenopausal women with breast
      cancer is increasing. We investigated interactions between the soy isoflavone,
      genistein, and an antiestrogen, tamoxifen (TAM), on the growth of estrogen (E)
      dependent breast cancer (MCF-7) cells implanted in ovariectomized athymic mice.
      We hypothesized that weakly estrogenic genistein negate/overwhelm the inhibitory
      effect of TAM on the growth of E-dependent breast tumors. Six treatment groups
      were used: control (C); 0.25 mg estradiol (E2) implant (E); E2 implant + 2.5 mg
      TAM implant (2.5 TE); E2 implant + 2.5 mg TAM implant + 1000 ppm genistein (2.5
      TEG); E2 implant + 5 mg TAM implant (5 TE), and E2 implant +5 mg TAM implant
      +1000 ppm genistein (5 TEG). Treatment with TAM (2.5 TE and 5 TE) suppressed E2
      stimulated MCF-7 tumor growth in ovariectomized athymic mice. Dietary genistein
      negated/overwhelmed the inhibitory effect of TAM on MCF-7 tumor growth, lowered
      E2 level in plasma, and increased expression of E-responsive genes (e.g., pS2,
      PR, and cyclin D1). Therefore, caution is warranted for postmenopausal women
      consuming dietary genistein while on TAM therapy for E-responsive breast cancer.

PMID- 11980636
TI  - Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via
      the proteosome pathway in prostate cancer cells.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor
      composed of alpha and beta subunits. HIF-1 is critically involved in cellular
      responses to hypoxia, glycolysis, and angiogenesis. Here, we show that treatment
      of prostate cancer PC-3 and LNCaP cells with the benzoquinone ansamycin
      geldanamycin, an Hsp90-specific inhibitor, induced degradation of HIF-1alpha
      protein in a dose- and time-dependent manner under both normoxia and hypoxia.
      This inhibition was also shown in other common cancer types tested. Rapid
      degradation of nuclear HIF-1alpha protein levels was accompanied by respective
      inhibition in HIF-1alpha functional transcription activity of VEGF. No difference
      between HIF-1alpha mRNA levels before or after geldanamycin treatment was found.
      Moreover, [35S]methionine pulse-chase analysis revealed that HIF-1alpha protein
      half-life was markedly decreased in the presence of geldanamycin compared with
      that in control. The geldanamycin-induced degradation of HIF-1alpha was reversed
      by proteosome inhibitors lactacystin and MG-132. We conclude that geldanamycin
      induces reduction of HIF-1alpha levels and its downstream transcriptional
      activity by accelerating protein degradation independent of O2 tension. Thus,
      benzoquinone ansamycin drugs and their derivatives, such as 17-allyl
      aminogeldanamycin, are excellent candidates as small molecule drug inhibitors of
      HIF-1 overexpression in cancer cells.

PMID- 11980637
TI  - Ku affects the ataxia and Rad 3-related/CHK1-dependent S phase checkpoint
      response after camptothecin treatment.
AB  - Camptothecin (CPT) that targets DNA topoisomerase I is one of the most promising
      broad-spectrum anticancer drugs in development today. The cytotoxicity of CPT is
      S phase (S)-specific because the collision of advancing replication forks with
      CPT-topoisomerase I-DNA complexes results in DNA damage. After DNA damage,
      proliferating cells could actively slow down the DNA replication through an S
      checkpoint to provide time for repair. We report now that there is an activated S
      checkpoint response in CPT-treated mammalian cells. This response is regulated by
      Ataxia and Rad3-related (ATR)/CHK1 pathway. Compared with their wild-type
      counterparts, CPT-treated Ku80-/- cells showed stronger inhibition of DNA
      replication. This stronger inhibition had no relationship with DNA-dependent
      protein kinase (DNA-PK) activity but correlated with the higher activities of ATR
      and the higher activities of CHK1 in such cells. Not only caffeine, the
      nonspecific inhibitor of ATR, or UCN-01, the nonspecific inhibitor of CHK1, but
      also the specific CHK1 antisense oligonucleotide abolished the stronger
      inhibition of DNA replication in CPT-treated Ku80-/- cells. These results in
      aggregate indicated that the stronger S checkpoint in CPT-treated Ku80-/- cells
      is regulated through the highly activated ATR/CHK1 pathway.

PMID- 11980638
TI  - Resveratrol induces prostate cancer cell entry into s phase and inhibits DNA
      synthesis.
AB  - Resveratrol has an apoptotic effect on a variety of cancer cells. Changes in cell
      cycle regulatory processes contributing to the antiproliferative effect of
      resveratrol remain largely unknown. Our studies revealed that, in androgen
      sensitive LNCaP cells, the effect of resveratrol on DNA synthesis varied
      dramatically depending on the concentration and the duration of treatment. In 1-h
      treated cells, resveratrol showed only an inhibitory effect on DNA synthesis,
      which increased with increasing concentration (IC50 = 20 microM). However, when
      treatment duration was extended to 24 h, we observed a dual effect of resveratrol
      on DNA synthesis. At 5 to 10 microM it caused a 2- to 3-fold increase in DNA
      synthesis, and at > or =15 microM, it inhibited DNA synthesis. The increase in
      DNA synthesis was seen only in LNCaP cells, but not in androgen-independent DU145
      prostate cancer cells or in NIH3T3 fibroblast cells. The resveratrol-induced
      increase in DNA synthesis was associated with enrichment of LNCaP cells in S
      phase, and a concurrent decrease in nuclear p21Cipl and p27Kip1 levels.
      Furthermore, consistent with the entry of LNCaP cells into S phase, there was a
      dramatic increase in nuclear Cdk2 activity associated with both cyclin A and
      cyclin E. Taken together, our observations indicate that LNCaP cells, treated
      with resveratrol, are induced to enter into S phase, but subsequent progression
      through S phase is limited by the inhibitory effect of resveratrol on DNA
      synthesis, particularly at concentrations above 15 microM. Therefore, this unique
      ability of resveratrol to exert opposing effects on two important processes in
      cell cycle progression, induction of S phase and inhibition of DNA synthesis, may
      be responsible for its apoptotic and antiproliferative effects.

PMID- 11980639
TI  - Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer:
      relationship to tumor biology and treatment outcome in surgically resected
      patients.
AB  - Hypoxia within head and neck squamous cell carcinoma (HNSCC) predicts a poor
      response to radiotherapy and poor prognosis. Hypoxia-inducible factor (HIF)-1 and
      HIF-2 are nuclear transcription factors that regulate the cellular response to
      hypoxia and are important for solid tumor growth and survival. Overexpression of
      HIF-1alpha and HIF-2alpha was demonstrated in three HNSCC cell lines under
      hypoxia and tumor tissue versus normal tissue (n = 20, HIF-1alpha, P = 0.023; HIF
      2alpha, P = 0.013). On immunostaining, HIF-1alpha and HIF-2alpha expression were
      localized to tumor nuclei; HIF-2alpha expression was also seen in tumor
      associated macrophages. Expression of HIF-1alpha in surgically treated patients
      with HNSCC (n = 79) was associated with improved disease-free survival (P =
      0.016) and overall survival (P = 0.027).

PMID- 11980640
TI  - Deficiency of Retinoblastoma gene in mouse embryonic stem cells leads to genetic
      instability.
AB  - Genetic instability has been recognized as a hallmark of human cancers.
      Retinoblastoma (Rb) tumor suppressor protein has an essential role in modulating
      cell cycle progression. However, there is no direct evidence supporting its role
      in maintaining genetic stability. Here, we developed a sensitive method to
      examine the level of chromosome instability by using retrovirus carrying both
      positive and negative selectable markers that integrated randomly into individual
      chromosomes, and the frequency of loss of this selectable chromosomal marker
      (LOM) in normal mammalian cells was measured. Our results showed that normal
      mouse embryonic stem (ES) cells had a very low frequency of LOMs, which was less
      than 10(-8)/cell/generation. In Rb-/- mouse ES cells, the frequency was increased
      to approximately 10(-5)/cell/generation, whereas in Rb+/- ES cells, the frequency
      was approximately 10(-7)/cell/generation. LOMs was mediated mainly through
      chromosomal mechanisms and not through point mutations. These results, therefore,
      revealed that Rb, with a haploinsufficiency, plays a critical role in the
      maintenance of chromosome stability. The mystery of why Rb heterozygous carriers
      have early-onset tumor formation with high penetrance can be, at least, partially
      explained by this novel activity.

PMID- 11980641
TI  - Neural Wiskott-Aldrich syndrome protein is involved in hepatocyte growth factor
      induced migration, invasion, and tubulogenesis of epithelial cells.
AB  - Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP family,
      regulates reorganization of the actin cytoskeleton through activation of the
      Arp2/3 complex. To date, most studies of N-WASP have focused on intracellular and
      morphological phenomena, such as vesicle transport and filopodium formation. We
      investigated the importance of N-WASP in epithelial morphogenesis, using Madin
      Darby canine kidney epithelial cells, which form branching tubules when cultured
      with hepatocyte growth factor (HGF) in collagen gel. We established MDCK cell
      lines that overexpress wild-type N-WASP (WT-NW) or a dominant-negative form of N
      WASP (DN-NW). WT-NW and parental Madin-Darby canine kidney cells formed branching
      tubules in collagen gel in response to HGF. However, formation of branching
      tubules was suppressed in DN-NW cells. During tubulogenesis, endogenous N-WASP
      accumulated at cell extensions protruding from the walls of the cysts and at the
      tips of the extending tubules. Gross cell morphology, cell-cell adhesion, cell
      polarity, and scattering in response to HGF were unaffected in WT-NW and DN-NW
      cells. In contrast, directed cell migration and HGF-induced invasion were
      significantly repressed in DN-NW cells. These results indicate that N-WASP
      regulates HGF-induced cell migration and invasion, which are required for
      epithelial tubulogenesis.

PMID- 11980642
TI  - Forced expression of the interferon regulatory factor 2 oncoprotein causes
      polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells.
AB  - The IFN regulatory factor-2 (IRF-2) oncoprotein controls the cell cycle-dependent
      expression of histone H4 genes during S phase and may function as a component of
      an E2F-independent mechanism to regulate cell growth. To investigate the role of
      IRF-2 in control of cell proliferation, we have constructed a stable FDC-P1 cell
      line (F2) in which expression of IRF-2 is doxycycline (DOX)-inducible, and a
      control cell line (F0). Both the F2 and F0 cell lines were synchronized in the G1
      phase by isoleucine deprivation, and IRF-2 was induced by DOX on release of cells
      from the cell cycle block. Flow cytometric analyses indicated that forced
      expression of IRF-2 has limited effects on cell cycle progression before the
      first mitosis. However, continued cell growth in the presence of elevated IRF-2
      levels results in polyploidy (>4n) or genomic disintegration (<2n) and cell
      death. Western blot analyses revealed that the levels of the cell cycle
      regulatory proteins cyclin B1 and the cyclin-dependent kinase (CDK)-inhibitory
      protein p27 are selectively increased. These changes occur concomitant with a
      significant elevation in the levels of the FAS-L protein, which is the ligand of
      the FAS (Apo1/CD95) receptor. We also found a subtle change in the ratio of the
      apoptosis-promoting Bax protein and the antiapoptotic Bcl-2 protein. Hence, IRF-2
      induces a cell death response involving the Fas/FasL apoptotic pathway in FDC-P1
      cells. Our data suggest that the IRF-2 oncoprotein regulates a critical cell
      cycle checkpoint that controls progression through G2 and mitosis in FDC-P1
      hematopoietic progenitor cells.

PMID- 11980643
TI  - Cyclooxygenase-2 overexpression in the skin of transgenic mice results in
      suppression of tumor development.
AB  - Significant evidence has accumulated suggesting that the inducible form of
      cyclooxygenase (COX-2), a central enzyme in the prostaglandin biosynthetic
      pathway, plays an important role in tumor development. To better understand the
      role of COX-2 in tumorigenesis, we generated transgenic mice that overexpress COX
      2 under control of the human keratin 14 promoter, which allows for expression in
      the epidermis and some other epithelia. Transgenic mice, referred to as K14.COX2
      mice, were readily distinguished from their nontransgenic littermates by the
      appearance of significant alopecia. Administration of a specific COX-2 inhibitor
      restored hair growth, indicating that the alopecia was attributable to elevated
      COX-2 enzymatic activity. Unexpectedly, COX-2 overexpression was found to
      protect, rather than sensitize, K14.COX2 mice to skin tumor development induced
      by an initiation/promotion protocol. K14.COX2 transgenics developed tumors at a
      much lower frequency than did their littermate controls (3.3% versus 93%,
      respectively, on a FVB background and approximately 25% versus 100%,
      respectively, on an ICR background) and presented with significantly reduced
      tumor burdens (average, 0.03 versus 12.7 tumors/mouse, respectively, on a FVB
      background and 0.5 versus 7.1 tumors/mouse, respectively, on an ICR background).
      Mice fed a COX-2 inhibitor in utero and as weanlings up to the time of promotion
      also showed a significant resistance to tumor development. These results clearly
      raise questions regarding the role of COX-2 and elevated prostaglandin levels in
      skin tumor development.

PMID- 11980644
TI  - Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding
      protein/p300-dependent and -independent mechanisms.
AB  - Treatment with retinoic acid (RA) or carnosol, two structurally unrelated
      compounds with anticancer properties, inhibited phorbol ester (PMA)-mediated
      induction of activator protein-1 (AP-1) activity and cyclooxygenase-2 (COX-2)
      expression in human mammary epithelial cells. The induction of COX-2
      transcription by PMA was mediated by increased binding of AP-1 to the cyclic AMP
      response element (CRE) of the COX-2 promoter. Inhibition of the histone
      acetyltransferase activity of CREB- binding protein (CBP)/p300 blocked the
      induction of COX-2 by PMA. Treatment with carnosol but not RA blocked increased
      binding of AP-1 to the COX-2 promoter. Because AP-1 binding was unaffected by RA,
      we investigated whether RA inhibited COX-2 transcription via effects on the
      coactivator CBP/p300. Treatment with RA stimulated an interaction between RA
      receptor-alpha and CBP/p300; a corresponding decrease in the interaction between
      CBP/p300 and c-Jun was observed. Importantly, overexpressing CBP/p300 or dominant
      negative RA receptor-alpha relieved the suppressive effect of RA on PMA-mediated
      stimulation of the COX-2 promoter. To elucidate the mechanism by which carnosol
      inhibited COX-2 transcription, its effects on protein kinase C (PKC) signaling
      were determined. Carnosol but not RA inhibited the activation of PKC, ERK1/2,
      p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinase.
      Overexpressing c-Jun but not CBP/p300 reversed the suppressive effect of carnosol
      on PMA-mediated stimulation of COX-2 promoter activity. Thus, RA acted by a
      receptor-dependent mechanism to limit the amount of CBP/p300 that was available
      for AP-1-mediated induction of COX-2. By contrast, carnosol inhibited the
      induction of COX-2 by blocking PKC signaling and thereby the binding of AP-1 to
      the CRE of the COX-2 promoter. Taken together, these results show that small
      molecules can block the activation of COX-2 transcription by distinct mechanisms.

PMID- 11980645
TI  - Involvement of membrane signaling in the bystander effect in irradiated cells.
AB  - We have shown previously that when confluent cultures of mammalian cells are
      exposed to very low fluences of alpha particles, fluences whereby only 1-3% of
      the cell nuclei are traversed by a particle, genetic effects, including specific
      gene mutations and sister chromatid exchanges, are induced in neighboring,
      nonirradiated ("bystander") cells (H. Nagasawa and J. B. Little, Cancer Res., 52:
      6394-6396, 1992; H. Nagasawa and J. B. Little, Radiat. Res., 152: 552-557, 1999).
      The present experiments were designed to determine whether signaling pathways
      arising in the cell membrane may mediate this effect. Cells were irradiated in
      the presence of Filipin, an agent that disrupts lipid rafts, effectively
      inhibiting membrane signaling, and the induction of sister chromatid exchange and
      HPRT mutations by very low fluences of alpha particles (mean doses 0.17-0.5 cGy)
      was measured. Filipin completely suppressed the induction of both genetic effects
      in bystander cells. After exposure to 10 cGy, when most mutations occurred in
      directly irradiated cells, no suppressive effect of Filipin was observed. These
      results suggest that membrane signaling may play an important role in the
      bystander effect of radiation. On the other hand, the effects in directly
      irradiated cells do not appear to be mediated via the cell membrane.

PMID- 11980646
TI  - Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts
      survival in stage I non-small cell lung cancer patients.
AB  - 90K, also known as Mac-2 binding protein, is a secreted glycoprotein that binds
      galectins, beta1-integrins, collagens, and fibronectin, and has some relevance in
      cell-cell and cell-extracellular matrix adhesion. Previous studies have shown
      that serum levels of 90K have prognostic value in several neoplasms. In the
      present study, the role of the expression of 90K as an adverse prognostic
      indicator in 72 pathological stage I non-small cell lung cancer patients was
      investigated immunohistochemically. All of the patients underwent complete
      surgical removal of the tumor. The median length of follow-up care was 54 months.
      High level of 90K expression (90K staining of > or =50% of the neoplastic cells)
      was observed in 20 of the 72 (28%) tumors. Expression of 90K was confirmed by
      ELISA. The results showed that a high expression of 90K correlates with adverse
      prognosis. Among patients with high 90K expression, the disease-free and overall
      survival rates were significantly lower than the same rates of those with low
      expression (P = 0. 0001 and P = 0. 0003, respectively). The incidence of distant
      metastases in the patients with high 90K expression (60%; 12 of 20 patients) was
      significantly higher than that of in the patients with low expression (21%; 11 of
      53 patients; P = 0.0038). The results of multivariate analysis confirmed that a
      high 90K expression was a significant factor to predict poor prognosis. We
      suggest that 90K expression could be a useful prognostic factor in patients with
      stage I non-small cell lung cancer, likely as an indicator of the metastatic
      propensity of the tumor.

PMID- 11980647
TI  - Selenium modulation of cell proliferation and cell cycle biomarkers in human
      prostate carcinoma cell lines.
AB  - Prostate cancer (PCA) is the most common histological malignancy and the second
      leading cause of cancer deaths among North American men. There has been
      considerable interest in the chemopreventative properties of selenium. In this
      study, we assessed whether selenium inhibits cell growth and associated cell
      cycle regulatory proteins. Human PCA cells (LNCaP, PC3, PC3-AR2, and PC3-M) were
      incubated with and without selenium (Seleno-DL-methionine, 150 microM) for 24,
      48, and 72 h. Cells were fixed and stained with propidium iodide for flow
      cytometry analysis. In parallel experiments, total protein was extracted,
      immunoprecipitated with cyclin E antibody, and analyzed by Western blot for the
      expression of cell cycle markers. Treatment with selenium caused G1 arrest and an
      80% reduction in the S phase of LNCaP with no effect on PC3. However, PC3 cells
      transfected with the androgen receptor (PC3-AR2) exhibited a G2/M arrest and a
      marked reduction (57%) in the S phase during cell cycle progression. In the
      analysis of cell cycle regulatory molecules, selenium-treated cells demonstrated
      a significant induction of cyclin-dependent kinase inhibitors Cip1/p21 and
      Kip1/p27. These data suggest that selenium possesses strong antiproliferative
      properties in regard to human PCA. This effect appears to be dependent on the
      presence of a functioning androgen receptor. This provides a theoretical basis
      for Phase III studies of selenium in PCA prevention.

PMID- 11980648
TI  - Prostate stem cell antigen as therapy target: tissue expression and in vivo
      efficacy of an immunoconjugate.
AB  - We conducted an expression analysis of prostate stem cell antigen (PSCA)in normal
      urogenital tissues, benign prostatic hyperplasia (n = 21), prostatic
      intraepithelial neoplasia (n = 33), and primary (n = 137) and metastatic (n = 42)
      prostate adenocarcinoma, using isotopic in situ hybridization on tissue
      microarrays. In normal prostate, we observe PSCA expression in the terminally
      differentiated, secretory epithelium; strong expression was also seen in normal
      urothelium. Forty-eight percent of primary and 64% of metastatic prostatic
      adenocarcinomas expressed PSCA RNA. Our studies did not confirm a positive
      correlation between level of PSCA RNA expression and high Gleason grade. We
      characterized monoclonal anti-PSCA antibodies that recognize PSCA expressed on
      the surface of live cells, are efficiently internalized after antigen
      recognition, and kill tumor cells in vitro in an antigen-specific fashion upon
      conjugation with maytansinoid. Unconjugated anti-PSCA antibodies demonstrated
      efficacy against PSCA-positive tumors by delaying progressive tumor growth in
      vivo. Maytansinoid-conjugated antibodies caused complete regression of
      established tumors in a large proportion of animals. Our results strongly suggest
      that maytansinoid-conjugated anti-PSCA monoclonal antibodies should be evaluated
      as a therapeutic modality for patients with advanced prostate cancer.

PMID- 11980649
TI  - ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal
      growth factor receptor tyrosine kinase.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase is a potential target for
      anticancer therapy. ZD1839 (Iressa) is a selective inhibitor of EGFR tyrosine
      kinase. In this study, we investigated the question as to whether the antitumor
      effect of ZD1839 is partly attributable to antiangiogenic activity and the
      potential mechanisms involved. Both ZD1839 and SU5416 [a vascular endothelial
      growth factor (VEGF)-receptor tyrosine kinase inhibitor] inhibited the migration
      of human umbilical vein endothelial cell cocultivated with EGF-stimulated cancer
      cells. ZD1839 also inhibited EGF-induced migration and the formation of tube-like
      structures by human microvascular endothelial cells. Moreover, ZD1839 almost
      completely blocked EGF-induced neovascularization of mice cornea, and SU5416
      partially blocked neovascularization. In contrast, ZD1839 did not inhibit VEGF
      induced angiogenesis. However, EGF-induced up-regulation of the angiogenic
      factors, VEGF and IL-8, was almost completely blocked by ZD1839. The antitumor
      effects of ZD1839 could, therefore, be mediated in part by the inhibition of
      tumor angiogenesis through direct effects on microvascular endothelial cells that
      express EGFR and also through reduced production of proangiogenic factors by
      tumor cells.

PMID- 11980650
TI  - Antivasculature effects of doxorubicin-containing liposomes in an intracranial
      rat brain tumor model.
AB  - Increased neovascularization and vascular hyperpermeability are integral
      processes in tumors, and various therapeutic strategies seek to reverse the
      angiogenic phenotype. Long-circulating liposomes extravasate in tumors such as
      the rat 9L gliosarcoma and accumulate in perivascular areas. Under such
      conditions, liposome-encapsulated doxorubicin (DOX) provides approximately 30%
      increase in life span, but free DOX is no more beneficial than a saline control.
      However, the relationship between drug deposition and therapeutic effect is
      understood poorly. In the present work, magnetic resonance (MR) and functional MR
      (fMR) imaging were used for noninvasive, serial evaluation of intracranial 9L
      tumor responses to repetitive doses of free DOX or DOX in sterically stabilized
      long-circulating liposomes (SSL-DOX). After multiple doses of SSL-DOX, MR imaging
      revealed the induction of intratumor hemorrhage in 63-75% of rats (n = 8). No
      hemorrhage was observed by MR imaging after a single dose of SSL-DOX, in normal
      brain regions in animals treated with free DOX (n = 3) or in saline controls (n =
      9). Histological sections from rats sacrificed immediately after MR imaging
      verified the putative hemorrhagic regions and revealed necrotic and apoptotic
      tumor cells surrounding the area of the hemorrhage. fMR maps were obtained by
      comparing paired images acquired during air and Carbogen (7% CO2 and 93% oxygen)
      breathing. These blood oxygenation level-dependent fMR maps showed enhanced image
      intensity after both single and multiple doses of SSL-DOX, which suggested
      increased and progressive vascular permeabilization. The results suggest that the
      breakdown of tumor vasculature induced by SSL-DOX may arise from the perivascular
      accumulation of liposomes in tumor and cytotoxic effects on tumor vascular
      endothelium.

PMID- 11980651
TI  - Selective targeting of angiogenic tumor vasculature by vascular endothelial
      cadherin antibody inhibits tumor growth without affecting vascular permeability.
AB  - Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific
      adhesion molecule that is localized exclusively at cell-cell contacts referred to
      as adherens junctions. VE-cadherin-mediated adhesion is crucial for proper
      assembly of vascular structures during angiogenesis as well as for maintenance of
      a normal vascular integrity. We have shown previously that a monoclonal antibody
      (BV13) to VE-cadherin not only inhibits the formation of vascular tubes during
      tumor angiogenesis but also disrupts adherens junctions of normal vasculature
      with a concomitant increase in vascular permeability. The goal of the current
      studies was to block VE-cadherin function during angiogenesis without disrupting
      existing junctions on normal endothelium. Using in vitro screening assays to test
      for functional blocking of adherens junction formation and in vivo assays to
      detect antibody effects on vascular permeability in normal tissues, we have
      identified a novel blocking antibody (E4G10) that inhibits VE-cadherin function
      during angiogenesis but does not disrupt existing adherens junctions on normal
      vasculature. E4G10 inhibited formation of vascular tubes in vivo in the Matrigel
      plug and corneal micropocket assays. E4G10 also inhibited tumor growth in three
      models of mouse and human tumors via an antiangiogenic mechanism. Examination of
      normal mouse and tumor tissues showed that E4G10 bound to endothelial cells in a
      subset of tumor vasculature but not to normal vasculature. Bromodeoxyuridine
      labeling experiments showed that E4G10 specifically targeted a subset of tumor
      endothelium that is undergoing active cell proliferation, which likely reflects
      the activated, angiogenic endothelium. These findings indicate that VE-cadherin
      can be selectively targeted during states of pathological angiogenesis, despite
      its ubiquitous distribution throughout the entire vasculature. Our data also
      suggest that antibody E4G10 recognizes VE-cadherin epitopes that are only
      accessible on endothelial cells forming new adherens junctions, such as in
      angiogenic tumor vasculature.

PMID- 11980652
TI  - Prostate-specific expression of the diphtheria toxin A chain (DT-A): studies of
      inducibility and specificity of expression of prostate-specific antigen promoter
      driven DT-A adenoviral-mediated gene transfer.
AB  - Diphtheria toxin (DT) is a potent inhibitor of protein synthesis. As little asa
      single molecule of DT can result in cell-cycle independent cell death. This
      profound potency has led to difficulties in the development of DT as a suicide
      gene in cancer gene therapy, because toxicity appears to be related primarily to
      the fidelity of basal gene expression and the yield of viral titer. We evaluated
      the feasibility of prostate-specific DT gene therapy by cloning the catalytic
      domain (A chain) of DT under the control of the prostate-specific antigen (PSA)
      promoter, the PSA promoter and enhancer, or the cytomegalovirus promoter. The
      data on expression of DT from the plasmid constructs demonstrate that the basal
      level of DT gene expression determines the toxicity. To better test the potential
      therapeutic efficacy of DT suicide gene therapy, we first developed a DT
      resistant adenoviral packaging line (293DTR). This allowed us to manufacture a
      relatively high titer adenoviral vector encoding the DT-A gene under the control
      of the PSA promoter and enhancer (Ad5PSE-DT-A) as well as an attenuated DT-A
      virus (Ad5PSE-tox176). In vitro studies showed that our viral constructs
      preferentially kill PSA-positive prostate cancer cells in the presence of
      exogenous androgen (R1881). In vivo studies showed that the nu/nu mice with PSA
      positive cancer cell LNCaP xenograft treated with wild-type DT-A virus had a
      rapid regression of tumors and survived over a year without tumor progression,
      whereas the attenuated DT-A virus restricted tumor growth for only 1 month. The
      same constructs had no significant effect on the non-PSA-secreting cell line DU
      145. These encouraging results suggest that DT-A viral gene transfer may
      ultimately have a therapeutic role in the treatment of advanced human prostate
      cancer.

PMID- 11980653
TI  - Glioma-associated hyaluronan induces apoptosis in dendritic cells via inducible
      nitric oxide synthase: implications for the use of dendritic cells for therapy of
      gliomas.
AB  - As a means of enhancing immunity to gliomas, we investigated local delivery of
      rat, bone marrow-derived dendritic cells (DCs) into rat 9L gliosarcoma tumors and
      into 9L tumors induced to undergo apoptosis by gamma knife radiosurgery. Contrary
      to other tumors, local delivery of DCs had no therapeutic effect on 9L gliomas,
      even when tumor apoptosis was induced via radiosurgery, which leads to efficient
      "loading" of the DCs with tumor antigen. To determine whether antigen-presenting
      cells, such as DCs, were viable in tumors, we carried out multiparametric
      staining of 9L tumors, using phycoerythrin-conjugated OX6 (MHC class II) or OX62
      (DC specific) and FITC-labeled Val-Ala-Asp-fluoromethyl ketone (FITC-VAD-FMK;
      activated caspases). It was determined that DCs were undergoing apoptosis in
      these tumors. We therefore sought to determine which glioma cell surface
      receptors or components of the extracellular matrix in gliomas influenced DC
      viability. Hyaluronan (HA) is a major component of glioma extracellular matrix
      and has been found to support tumor cell migration and metastasis. However, its
      influence on the immune system, and particularly on DCs, via its receptor CD44 is
      not well documented. Using reverse transcription-PCR, Northern blot, and Western
      blot analyses, we determined that HA stimulated production of inducible nitric
      oxide synthase (iNOS) in DCs. NO production by HA-stimulated DCs was then
      verified biochemically. NO production was dependent on the size of HA;
      intermediate HA fragments had the greatest capacity to induce NO production in
      DC, whereas completely digested HA oligosaccharides failed to induce NO.
      Furthermore, N-monomethyl-L-arginine, an inhibitor of iNOS, completely blocked HA
      induced NO production by DCs. Because induction of NO results in the induction of
      apoptosis in macrophages as well as other cells, DCs treated with HA were
      examined for apoptosis in terminal deoxynucleotidyl transferase (TdT)-mediated
      dUTP biotin nick-end labeling assays. It was demonstrated that HA induced
      apoptosis in DCs and that induction of apoptosis was dependent on the production
      of NO because it was entirely inhibited by N-monomethyl-L-arginine. Using flow
      cytometric analyses with FITC-VAD-FMK, which is specific for activated caspases,
      we also determined that induction of apoptosis in DCs with HA could be titrated.
      Coincubation of 9L tumor cells with DCs was found to induce apoptosis in DCs as
      indicated by fluorescent staining with FITC-VAD-FMK. Specificity of this reaction
      for CD44-HA interactions was determined by pretreatment of DCs with anti-CD44 or
      pretreatment of 9L tumor cells with hyaluronidase, which blocked the induction of
      apoptosis in DCs. These data indicate that HA expressed by gliomas may contribute
      to their immunosuppressive effects by promoting apoptosis among professional
      antigen-presenting cells such as DCs via iNOS induction after CD44-HA
      interactions.

PMID- 11980654
TI  - Identification of CD70-mediated apoptosis of immune effector cells as a novel
      immune escape pathway of human glioblastoma.
AB  - Interactions of CD70, a tumor necrosis factor-related cell surface ligand and its
      receptor, CD27, are thought to play an important role for T-, B-, and natural
      killer-cell activation. However, ligation of CD27 can also induce apoptosis.
      Human glioblastoma is paradigmatic for cancer-associated immunosuppression. We
      identified CD70 as a radioinducible gene in U87 MG glioma cells. A screening of a
      panel of human glioma cell lines revealed that 11 of 12 cell lines expressed CD70
      mRNA and protein. Two human neuroblastoma cell lines did not express CD70. CD70
      mRNA expression was enhanced by irradiation in 8 of 12 glioma cell lines in a p53
      independent manner. No alteration in CD70 expression was observed after glioma
      cell exposure to cytotoxic drugs such as lomustine. CD70 protein was also
      detected by immunocytochemistry in 5 of 12 glioblastomas and 3 of 4 anaplastic
      astrocytomas in vivo. CD27 expression was not detected in any glioma cell line,
      and there was no evidence for autocrine or backward signaling of the CD70 system
      in human glioma cells. Unexpectedly, CD70 expressed on glioma cells did not
      increase the immunogenicity of glioma cells in vitro. In contrast, CD70-positive
      glioma cells induced apoptosis in peripheral blood mononuclear cells (PBMCs) in a
      CD70-dependent manner. Neutralization of CD70 expressed on glioma cells prevented
      apoptosis and enhanced the release of tumor necrosis factor-alpha in cocultures
      of glioma cells and PBMCs. The effects of CD70-expressing glioma cells on PBMCs
      were mimicked by agonistic CD27 antibodies. Conversely, the shedding of CD27 by
      PBMCs was identified as a possible escape mechanism from glioma cell-induced CD70
      dependent apoptosis. Thus, induction of B-cell and T-cell apoptosis via
      interactions of CD70 expressed on glioma cells and CD27 expressed on B and T
      cells may be a novel way for the immune escape of malignant gliomas.

PMID- 11980655
TI  - Identification of HLA DR7-restricted epitopes from human telomerase reverse
      transcriptase recognized by CD4+ T-helper cells.
AB  - CD4+ T cells play critical roles in initiating, regulating, and maintaining
      antitumor immune responses. One way to improve current tumor vaccines that mainly
      induce CTLs would be to activate antigen-specific CD4+ T cells that recognize MHC
      class II restricted tumor associated antigens. Human telomerase reverse
      transcriptase (hTRT) is preferentially expressed by various tumors and,
      therefore, could be a universal tumor antigen. In this study, we used a combined
      approach of using the prediction software TEPITOPE to select class II epitope
      candidates and in vitro T-cell biological analysis to identify class II
      restricted epitope(s) in hTRT. We first identified several HLA-DR7-restricted
      class-II epitope candidates in hTRT by examining human T-cell responses to
      synthetic peptides. We then characterized these HLA-DR7-restricted hTRT epitope
      candidates by establishing and analyzing peptide-specific T-cell clones. It was
      demonstrated that CD4+ T cells specific for the HLA-DR7-restricted hTRT(672)
      epitope (RPGLLGASVLGLDDI) can respond to naturally processed hTRT proteins.
      Furthermore, the hTRT(672)-specific T cells recognized hTRT antigen from various
      tumors, including prostate cancer, breast cancer, melanoma, and leukemia. Thus,
      the identification of the naturally processed HLA-DR7-restricted hTRT epitope,
      together with the previous finding of class I-restricted hTRT epitopes, provide a
      basis for the combined application of class I- and II-restricted hTRT epitopes to
      induce potent, long-term CD4+ and CD8+ T-cell responses against a broad spectrum
      of tumors.

PMID- 11980656
TI  - Immunotherapy with interleukin-10 depends on the CXC chemokines inducible protein
      10 and monokine induced by IFN-gamma.
AB  - The cytokine interleukin (IL)-10 has potent antitumor activity in many model
      systems when expressed locally at very high levels from the time of tumor
      transplantation. We now demonstrate that systemic administration of recombinant
      human IL-10 to animals bearing established highly malignant mammary tumors also
      leads to significant growth inhibition. We had shown previously that expression
      of the CXC chemokines Mig (monokine induced by IFN-gamma) and IP-10 (inducible
      protein 10) is observed in IL-10 transduced but not neo-vector control tumors. We
      now demonstrate that treatment of IL-10-tumor-bearing mice with antibodies to
      either chemokine partially reverses the therapeutic effect of IL-10. Tumor growth
      in animals treated with both antibodies is comparable with that of vector control
      tumors. Direct transduction of Mig cDNA into the parental tumor cell line before
      transplantation also results in smaller tumors. This tumor growth inhibition is
      associated with increased numbers of CD4+ cells, consistent with a T-cell
      chemoattractant activity for Mig. No change in vascularization, as indicated by
      CD31+ cells, was observed in either Mig or IL-10-transfected tumors. Thus, an
      antiangiogenic activity for either cytokine could not be confirmed. Mig and IP-10
      are critical to the therapeutic response resulting from high levels of IL-10,
      and, furthermore, Mig as a single agent also has tumor-inhibitory activity in a
      model of breast cancer.

PMID- 11980657
TI  - Human CD4+ effector T cells mediate indirect interleukin-12- and interferon-gamma
      dependent suppression of autologous HLA-negative lung tumor xenografts in severe
      combined immunodeficient mice.
AB  - A human/severe combined immunodeficient mouse chimeric model was used to
      demonstrate that peripheral blood leukocytes (PBLs) from a patient with lung
      cancer completely suppress the growth of an autologous tumor in a PBL dose
      dependent fashion repeatedly and over a 4-year period. Suppression of the
      patient's tumor required CD4+ T cells, CD56+ natural killer cells, and CD14+
      monocytes/macrophages, but was completely independent of CD8+ T cells. The CD4+
      effector cells promoted tumor killing indirectly because direct tumor recognition
      and killing are precluded by the absence of MHC class I and II molecules on the
      tumor cells. Tumor suppression was found to require both human interleukin-12 (IL
      12) and IFN-gamma, which were produced and released by the patient's monocytes
      and T cells, respectively. These results establish that human CD4+ T cells
      present in the peripheral blood of a patient with lung cancer are able to
      orchestrate cytokine-dependent killing of an autologous MHC-negative tumor
      indirectly and without codependence on CD8+ T cells. We conclude that human tumor
      suppression is achieved in vivo even in the absence of MHC molecules on tumor
      cells. This tumor suppression is mediated indirectly by cytokines produced by the
      patient's PBLs that ultimately initiate tumor killing via several, presently
      incompletely defined mechanisms.

PMID- 11980658
TI  - Expression of mitotic spindle checkpoint protein hsMAD1 correlates with cellular
      proliferation and is activated by a gain-of-function p53 mutant.
AB  - Human mitotic arrest deficiency protein 1, hsMAD1, is a component of the mitotic
      spindle assembly checkpoint (MSC) that monitors fidelity of chromosomal
      segregation and guards against emergence of cellular aneuploidy. Because
      aneuploidy is a pervasive characteristic of human cancers, understanding how MSC
      genes are regulated is important. Here, we have analyzed human genomic sequences
      upstream of the 5' most hsMAD1 coding exon and have identified a 1.5-kb fragment
      with promoter activity. The hsMad1 promoter, consistent with characteristics of
      housekeeping genes, is highly GC rich and is devoid of a TATA-box. Mutational
      analyses revealed a core region spanning -73 to -31 as being essential for hsMad1
      transcription. Surprisingly, although MSC function, prototypically induced by
      microtubule inhibitors, is active selectively during mitosis, we found the hsMad1
      promoter to be expressed predominantly in G1 and to respond not to microtubule
      inhibitor but to mitogenic stimulus. In primary, as well as transformed cells,
      intracellular levels of hsMAD1 correlated with the proliferative status of cells.
      The hsMad1 promoter was also activated preferentially by a gain-of-function p53
      mutant. Taken together, our results suggest that hsMAD1 might link p53 function
      to the generation of cellular aneuuploidy and that heightened activation of
      hsMad1 by gain-of-function p53 mutants could contribute to the worse prognosis of
      certain cancers.

PMID- 11980659
TI  - Targets of gene amplification and overexpression at 17q in gastric cancer.
AB  - DNA copy number gains and amplifications at 17q are frequent in gastriccancer,
      yet systematic analyses of the 17q amplicon have not been performed. In this
      study, we carried out a comprehensive analysis of copy number and expression
      levels of 636 chromosome 17-specific genes in gastric cancer by using a custom
      made chromosome 17-specific cDNA microarray. Analysis of DNA copy number changes
      by comparative genomic hybridization on cDNA microarray revealed increased copy
      numbers of 11 known genes (ERBB2, TOP2A, GRB7, ACLY, PIP5K2B, MPRL45, MKP-L,
      LHX1, MLN51, MLN64, and RPL27) and seven expressed sequence tags (ESTs) that
      mapped to 17q12-q21 region. To investigate the genes transcribed at the 17q, we
      performed gene expression analyses on an identical cDNA microarray. Our
      expression analysis showed overexpression of 8 genes (ERBB2, TOP2A, GRB2, AOC3,
      AP2B1, KRT14, JUP, and ITGA3) and two ESTs. Of the commonly amplified
      transcripts, an uncharacterized EST AA552509 and the TOP2A gene were most
      frequently overexpressed in 82% of the samples. Additional studies will be
      initiated to understand the possible biological and clinical significance of
      these genes in gastric cancer development and progression.

PMID- 11980660
TI  - RhoA-dependent murine prostate cancer cell proliferation and apoptosis: role of
      protein kinase Czeta.
AB  - We previously showed that RhoA played an important role in the proliferation of
      murine We prostate cancer (TRAMP) cells (P. M. Ghosh et al., Oncogene, 18: 4120
      4130, 1999). Untransfected TRAMP cells as well as those expressing constitutively
      active RhoA (Q63L) mutant protein (Q63L cells) were highly proliferative. In
      contrast, TRAMP cells expressing dominant-negative RhoA (T19N) mutant protein
      (T19N cells) were slow growing. In this study, we showed, in addition, that T19N
      cells displayed reduced rates of apoptotic cell death in response to serum
      deprivation, compared with TRAMP and Q63L cells, and we studied the mechanisms of
      the effects of RhoA on TRAMP cell proliferation and apoptosis. Both proliferation
      and apoptosis of TRAMP and Q63L cells were dependent on the activation of
      phosphatidylinositol 3-kinase (PI3K). The ubiquitous mitogen-activated Ser/Thr
      kinase, p70S6 kinase, a downstream effector of PI3K, was overexpressed in TRAMP
      and Q63L cells. Another PI3K effector, the cell survival protein Akt, displayed
      increased activity in T19N cells, which did not express active RhoA, compared
      with TRAMP and Q63L cells. The atypical protein kinase C (PKC) isoform PKCzeta,
      which is downstream of PI3K, was activated in cells expressing active RhoA. In
      addition, expression of constitutively activated PKCzeta in TRAMP cells enhanced
      proliferation and p70S6 kinase phosphorylation, whereas the inhibition of PKCzeta
      activation resulted in activation of Akt and enhanced cell survival. Thus, the
      effects of RhoA on TRAMP cell proliferation and apoptosis may be mediated by
      PKCzeta.

PMID- 11980661
TI  - Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice.
AB  - Loss of heterozygosity on human chromosome 3p21.3 is a frequent occurrence in
      many tumor types. In a previous study, our laboratory demonstrated that an 80-kb
      P1 clone from chromosome 3 suppresses the tumorigenicity of the mouse
      fibrosarcoma cell line A9. Two cDNAs corresponding to genes encoded on this P1
      clone, semaphorin 3F (SEMA3F) and N23, were tested for their effects on in vitro
      and in vivo growth characteristics after transfection into mouse A9 cells.
      Transfection of SEMA3F cDNA resulted in complete loss of tumorigenicity in nude
      mice, whereas transfection of N23 had no effect. Moreover, SEMA3F also functioned
      to block apoptosis of transfected A9 cells treated with Taxol or Adriamycin. The
      human ovarian adenocarcinoma cell line HEY showed a similar result as A9 cells,
      but the small cell lung cancer line GLC45 was unaffected by expression of SEMA3F.

PMID- 11980662
TI  - The role of thymidylate synthase induction in modulating p53-regulated gene
      expression in response to 5-fluorouracil and antifolates.
AB  - Thymidylate synthase (TS) is a critical target for chemotherapeutic agents such
      as 5-fluorouracil (5-FU) and antifolates such as tomudex (TDX),multitargeted
      antifolate, and ZD9331. Using the MCF-7 breast cancer line, we have developed p53
      wild-type (M7TS90) and null (M7TS90-E6) isogenic lines with inducible TS
      expression (approximately 6-fold induction compared with control after 48 h). In
      the M7TS90 line, inducible TS expression resulted in a moderate approximately 3
      fold increase in 5-FU IC-50(72 h) dose and a dramatic >20-fold increase in the IC
      50(72 h) doses of TDX, multitargeted antifolate, and ZD9331. S-phase cell cycle
      arrest and apoptosis induced by the antifolates were abrogated by TS induction.
      In contrast, cell cycle arrest and apoptosis induced by 5-FU was unaffected by TS
      expression levels. Inactivation of p53 significantly increased resistance to 5-FU
      and the antifolates with IC-50(72 h) doses for 5-FU and TDX of >100 and >10
      microM, respectively, in the M7TS90-E6 cell line. Furthermore, p53 inactivation
      completely abrogated the cell cycle arrest and apoptosis induced by 5-FU. The
      antifolates induced S-phase arrest in the p53 null cell line; however, the
      induction of apoptosis by these agents was significantly reduced compared with
      p53 wild-type cells. Both inducible TS expression and the addition of exogenous
      thymidine (10 microM) blocked p53 and p21 induction by the antifolates but not by
      5-FU in the M7TS90 cell line. Similarly, inducible TS expression and exogenous
      thymidine abrogated antifolate but not 5-FU-mediated up-regulation of Fas/CD95 in
      M7TS90 cells. Our results indicate that in M7TS90 cells, inducible TS expression
      modulates p53 and p53 target gene expression in response to TS-targeted
      antifolate therapies but not to 5-FU.

PMID- 11980663
TI  - Point mutations and deletions in the znfn1a1/ikaros gene in chemically induced
      murine lymphomas.
AB  - The Znfn1a1 gene encodes a zinc finger protein called Ikaros, which is
      criticalfor T-cell development and differentiation. The execution of normal
      function of Ikaros requires sequence-specific DNA binding, transactivation, and
      dimerization domains. In this study, exons 3-5 and exon 7 of the Znfn1a1 gene
      that encode the functional domains of Ikaros were analyzed for point mutations
      and deletions in murine lymphomas induced by 1,3-butadiene, 2',3'
      dideoxycytidine, or phenolphthalein. Missense and frameshift mutations were
      identified in 11% (11 of 104) of the tumors. Interestingly, 8 of the mutations
      were identified in the NH2-terminal zinc finger motifs, which are crucial for the
      DNA-binding function of Ikaros. The other 3 samples carried frameshift mutations
      in exon 7 that resulted in truncations and abrogation of both transactivation and
      dimerization domains. One tumor with a missense mutation in the DNA-binding
      domain also displayed a 45-bp deletion in the dimerization domain. Southern
      analysis disclosed interstitial homozygous deletions in the functional domains of
      Ikaros in 4% (3 of 68) of the lymphomas examined. Allelic losses on markers
      surrounding the Znfn1a1 gene were detected in 27% (12 of 45) of the tumors
      analyzed. However, only 2 tumors with allelic losses also showed mutations in the
      Znfn1a1 gene, indicating that other tumor suppressor genes located on this region
      might be involved as well. Our results suggest inactivation of Ikaros in a subset
      of chemically induced lymphomas and additionally support the contention of tumor
      suppressor activity for Ikaros.

PMID- 11980664
TI  - Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer
      and studies of its effect on protein function.
AB  - NKX3.1, a member of the NK class of homeodomain proteins, is expressed primarily
      in the adult prostate and has growth suppression and differentiating effects in
      prostate epithelial cells. A C-->T polymorphism at nucleotide 154 (NKX3.1 C154T)
      is present in approximately 11% of healthy men with equal distribution among
      whites and blacks. In a cohort of 1253 prostate cancer patients and age-matched
      controls, the presence of the polymorphism was associated with a 1.8-fold risk of
      having stage C or D prostate cancer or Gleason score > or =7 (confidence
      interval, 1.01-3.22). The NKX3.1 C154T polymorphism codes for a variant protein
      that contains an arginine-to-cysteine substitution at amino acid 52 (R52C)
      adjacent to a protein kinase C phosphorylation site at serine 48. Substitution of
      cysteine for arginine 52 or of alanine for serine 48 (S48A) reduced
      phosphorylation at serine 48 in vitro and in vivo. Phosphorylation of wild-type
      NKX3.1, but not of NKX3.1 R52C or NKX3.1 S48A, diminished binding in vitro to a
      high-affinity DNA binding sequence. NKX3.1 also serves as a transcriptional
      coactivator of serum response factor. Treatment of cells with 12-O
      tetradecanoylphorbol-13-acetate to phosphorylate NKX3.1 had no effect on NKX3.1
      coactivation of serum response factor. Neither the R52C nor the S48A substitution
      affected serum response factor coactivation by NKX3.1 We conclude that the
      polymorphic NKX3.1 allele codes for a variant protein with altered DNA binding
      activity that may affect prostate cancer risk.

PMID- 11980665
TI  - Tenascin-C promotes microvascular cell migration and phosphorylation of focal
      adhesion kinase.
AB  - Enhanced expression of tenascin-C (TN-C) at the invasive edges of glioblastoma
      multiforme in close association with vascular sprouts, suggests a role for TN-C
      in microvascular cell migration. To test this hypothesis, we studied the
      migration of endothelial cells in vitro. In an aggregate migration assay, bovine
      retinal endothelial cells (BRECs) and human umbilical vein endothelial cells
      spread and migrated similarly on TN-C or fibronectin (FN). In contrast, U251 MG
      glioma cells migrated less on TN-C than on FN. Morphological features of U251 MG
      glioma cells on TN-C included poor cell spreading and short processes. In
      contrast, on FN, U251 MG glioma cells spread and exhibited long radial processes.
      Using a transmembrane migration assay, we observed that BREC adhesion was similar
      on TN-C or FN, whereas U251 MG glioma cells adhered better to FN than to TN-C. In
      addition, BRECs migrated more across the membrane toward regions coated with TN-C
      than FN, and conversely, U251 MG glioma cells migrated more toward FN than TN-C.
      Migration of endothelial and glioma cells toward TN-C or FN occurred in a dose
      dependent manner and was strongly dependent on cell adhesion. In this assay,
      ultrastructural study revealed the migrating phenotype of the endothelial cells
      through the micropores of the membrane and their spread morphology on TN-C.
      Moreover, in situ hybridization revealed specific expression of TN-C in migrating
      microvascular cells in a cerebral microvascular ring assay. Finally in a
      phosphorylation assay, TN-C enhanced focal adhesion kinase phosphorylation of
      BRECs, but not of U251 MG glioma cells, and FN enhanced focal adhesion kinase
      phosphorylation of both BRECs and U251 MG cells. The expression of TN-C by
      migrating endothelial cells and the promotion of endothelial cell adhesion and
      migration by TN-C suggest a potential role for TN-C in pathological angiogenesis.

PMID- 11980666
TI  - Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in
      human colon cancer and transformed rodent cells.
AB  - Src has been implicated in the development and progression of human colon cancer.
      Because the capacity for tumor cells to dissociate from the primary tumor is a
      critical step in the development of metastases, the effect of a naturally
      occurring, activated Src-531 on intercellular adhesion was examined. Homotypic
      adhesion was assessed using dissociation assays on Src-transformed rat
      fibroblasts and human colon cancer cell lines. The data indicate that both rodent
      and human cells expressing the mutant Src protein display up to 7-fold less
      homotypic adhesion than do wild-type cells (P < 0.01). Experiments demonstrated
      that cadherin was phosphorylated in cells transfected with activated Src and that
      cadherin/catenin complexes were disrupted as a result. Experiments using dominant
      negative (DN) Src or an Src-specific inhibitor (PD 180970), demonstrated that
      adhesion was restored when Src activity was inhibited in Src-531 transfectants,
      confirming that Src is a causal factor in the decreased homotypic adhesion
      observed. In addition, DN Ras, DN focal adhesion kinase (FAK), but not Stat3beta,
      restored intercellular adhesion, which suggested that Ras and FAK may be
      downstream effectors of Src-mediated homotypic adhesion. Collectively, these data
      support a role for Src, Ras, and FAK in the regulation of intercellular adhesion,
      which may in turn regulate metastatic potential of human colon cancer cells.

PMID- 11980667
TI  - Multivariate analysis of chromosomal imbalances in breast cancer delineates
      cytogenetic pathways and reveals complex relationships among imbalances.
AB  - More than 550 breast adenocarcinomas with clonal chromosomal abnormalities have
      been reported. Although the aberration pattern is clearly nonrandom, no specific
      primary or secondary karyotypic abnormality has been identified, and furthermore
      the chronological order in which the aberrations appear during disease
      progression is not well known. The high degree of karyotypic complexity in
      epithelial tumors such as breast cancer is one reason why our understanding of
      the sequential order of cytogenetic evolution is unclear. To overcome some of
      these difficulties, we have used several statistical methods that allow
      identification and interpretation of karyotypic pathways. These methods were
      applied on 538 breast cancer karyotypes. The distribution of the number of
      imbalances/tumor showed a monomodal appearance, indicating that one single mode
      of karyotypic evolution is operating in this tumor type. We show that there
      exists a temporal order with respect to the appearance of chromosomal imbalances.
      The imbalances +1pq, 1q-, 3p-, and +7 appear earlier than expected from random
      events, and two cytogenetic pathways, one initiated by +1q and followed by 11q-
      and -22, the other initiated by either 3p- or 1q- and followed by 1p-, 3q-, and
      6q-, can be discerned. We also show that +7 and +8q behave independently of the
      other imbalances and cannot, by simple means, be incorporated in the identified
      pathway scheme. Although the cytogenetic pathways are well separated at earlier
      stages, they later converge and include a common set of late imbalances.

PMID- 11980668
TI  - Comparison of accumulated allele loss between primary tumor and lymph node
      metastasis in stage II non-small cell lung carcinoma: implications for the timing
      of lymph node metastasis and prognostic value.
AB  - Although the Tumor-Node-Metastasis staging of non-small cell lung carcinoma
      (NSCLC) is the most effective predictor of survival, the clinical outcome of
      patients at each stage is variable on an individual case basis. We tested the
      value of incorporating information about the tumor heterogeneity of NSCLC into
      microsatellite allelotyping in a cohort of 48 node-positive stage II patients
      (T1N1M0 and T2N1M0). Microsatellite allelotyping involved microdissection of the
      invasive component of primary tumor and lymph node metastasis at multiple target
      sites followed by loss of heterozygosity (LOH) analysis at specific regions on
      chromosomes 1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, and 18q using 16 markers. All
      microsatellites manifested LOH ranging from 44 to 76% in primary tumor and showed
      various degree of heterogeneity between primary tumor and lymph node metastasis.
      LOH on 3p and 5q in the lymph node metastases was associated significantly with
      shortened survival of the patients (P = 0.033 and 0.004, respectively), whereas
      no single LOH in the primary tumors showed association with prognosis. For the
      analysis of the accumulated load of allele loss, fractional allele loss (FAL) was
      calculated for each sample. The maximal FAL of lymph node metastasis was
      significantly lower than that of primary tumor (P = 0.0015), possibly reflecting
      the early lymphatic spread. High maximal FAL of lymph node metastasis was
      significantly correlated with an adverse outcome (P = 0.012), whereas maximal FAL
      of primary tumor did not show any prognostic significance (P = 0.552). A
      composite mutational profile for each patient based on the allelotyping of the
      primary tumor and lymph node deposits may make a significant contribution to a
      more accurate prognosis of stage II NSCLC.

PMID- 11980669
TI  - Partial depletion of intracellular ATP mediates the stress-survival function of
      the PCPH oncoprotein.
AB  - Promotion of cellular resistance to stressful stimuli, including ionizing
      radiation and chemotherapeutic drugs, contributes to the transforming activity of
      the PCPH oncogene. The mechanism of this action, however, has remained unknown.
      Consistent with its intrinsic ATP diphosphohydrolase activity, expression of the
      PCPH oncoprotein in cultured cells has now been shown to result in partial
      depletion of intracellular ATP and consequent inhibition of the c-JUN NH2
      terminal kinase-mediated stress signaling pathway. Supplementation of cells
      expressing the PCPH oncoprotein with exogenous ATP restored both stress-response
      signaling and sensitivity to cisplatin-induced apoptosis. In contrast,
      overexpression of the wild-type PCPH protein had a minimal effect on stress
      induced signaling and on the cellular ATP content and did not protect cells from
      apoptosis. These results suggest that the PCPH oncoprotein confers resistance to
      stressors by reducing the cellular ATP concentration to levels below those
      required for optimal stress-induced signaling and apoptosis. Treatment with
      adenosine or nucleoside analogues may thus enhance the response to radiation or
      chemotherapy of tumors that express the PCPH oncogene.

PMID- 11980670
TI  - DD3(PCA3), a very sensitive and specific marker to detect prostate tumors.
AB  - We identified DD3(PCA3) as one of the most prostate cancer-specific genes at
      present (M. J. Bussemakers et al. Cancer Res., 59: 5975-5979, 1999).
      Consequently, DD3(PCA3) is an interesting candidate for use as a diagnostic
      and/or prognostic marker. In this study we developed a method for the accurate
      quantification of DD3(PCA3) mRNA, using real-time quantitative reverse
      transcription-PCR. DD3(PCA3) was expressed at low levels in normal prostate but
      not in 21 selected other normal tissues, blood, or 39 tumor samples other than
      prostate. The diagnostic and prognostic value of DD3(PCA3) in normal,
      hyperplastic, and malignant prostate tissues was determined and compared with
      another promising tumor marker for prostate cancer, telomerase reverse
      transcriptase (hTERT gene), the expression of which is related to telomerase
      activity. Sensitivity and specificity estimates for both genes were calculated as
      the area under the receiver-operating characteristics curve (AUC-ROC). DD3(PCA3)
      (AUC-ROC, 0.98) demonstrated better diagnostic efficacy than hTERT (AUC-ROC,
      0.88). Moreover, the median increase in mRNA expression in tumor tissues compared
      with nonmalignant prostate tissues was much higher for DD3(PCA3) (34-fold) than
      for hTERT (6-fold). In tumor tissues, the median expression of DD3(PCA3) was much
      higher than hTERT (5849 versus 10 normalized mRNA copies). A significant
      relationship was observed only between tumor stage and hTERT gene expression. We
      conclude that expression of the DD3(PCA3) gene is a very sensitive and specific
      marker for the detection of prostate tumor cells in a high background of normal
      (prostate) cells. Consequently, DD3 measurements may be used for clinical
      application in prostate needle biopsies or bodily fluids such as blood,
      ejaculate, urine, or prostate massage fluid.

PMID- 11980671
TI  - Focal adhesion kinase enhances signaling through the Shc/extracellular signal
      regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples.
AB  - Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that on activation
      generates signals that can modulate crucial cell functions, including cell
      proliferation, migration, and survival. In vitro, overexpression of FAK has been
      shown to promote cell proliferation by signaling through the Ras/mitogen
      activated protein kinase cascade in several cell types. We have shown previously
      that overexpression of exogenous FAK lacking alternative splicing in malignant
      astrocytoma clones injected intracerebrally into SCID mouse brains promotes tumor
      cell proliferation. Here, we show that in anaplastic astrocytoma biopsy samples,
      FAK is expressed as an unspliced variant and migrates with a faster mobility
      similar to that observed in embryonic brain. Compared with nonneoplastic adult
      brain biopsies, the levels of FAK protein are elevated as are its levels of
      activation as assessed by autophosphorylation and overall tyrosine
      phosphorylation. The activity of Src kinase in these tumors is also elevated, as
      well as the activity of Src kinase associated with FAK; the latter may result in
      enhanced Src kinase phosphorylation of FAK. Phosphorylated Shc is associated with
      FAK in the anaplastic astrocytoma biopsy samples and in astrocytoma cells
      overexpressing FAK in vitro but not in nonneoplastic brain biopsy samples.
      Elevated extracellular signal-regulated kinase-2 activation and elevated
      expression of cyclins D and E are also found in anaplastic astrocytoma biopsy
      samples. These data provide evidence that the increased FAK activity in these
      tumors contributes to phosphorylation of Shc and likely to the promotion of Ras
      activity, extracellular signal-regulated kinase-2 activation, and cell
      proliferation in vivo.

PMID- 11980672
TI  - Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the
      mevalonate pathway.
AB  - Breast and prostate cancer preferentially metastasize in the skeleton, inducing
      locally increased bone resorption by osteoclasts. Bisphosphonates (BPs), potent
      inhibitors of osteoclasts and bone resorption, are able to reduce metastatic bone
      lesions, but the metastasis-related cellular target molecules for BPs have not
      yet been identified. In osteoclasts, nitrogen-containing BPs inhibit the function
      of the mevalonate pathway, impairing the prenylation and activation of small
      GTPases. In addition, direct effects of BPs on cancer cells have been suggested.
      In the present study, the effects of two clinically used BPs, the amino-BP
      alendronate and clodronate, on adhesion, invasion, and migration of human PC-3
      prostate cancer cells were examined in vitro. We also studied the possible role
      of the mevalonate pathway in invasion and migration of PC-3 cells using the beta
      hydroxy-beta-methylglutaryl-CoA reductase inhibitor mevastatin and the mevalonate
      pathway intermediates mevalonate (mevalonic acid lactone), geranylgeraniol, and
      trans-trans-farnesol. The results demonstrate that alendronate pretreatment very
      effectively inhibited in vitro invasion of prostate cancer cells in a dose
      dependent manner, with an IC50 as low as approximately 1 pM. The inhibition was
      similar to that of mevastatin. Clodronate also inhibited invasion, but the IC50
      was 0.1 microM. Importantly, geranylgeraniol and trans-trans-farnesol reversed
      the inhibitory effect of alendronate and mevastatin but not the clodronate
      induced inhibition of invasion. Alendronate pretreatment also inhibited
      migration, which was partially reversed by geranylgeraniol and trans-trans
      farnesol. Adhesion of PC-3 cells to various matrices was reduced, and their F
      actin organization was changed. Alendronate pretreatment also inhibited invasion
      of human Du-145 prostate and MDA-MB-231 breast cancer cells. As a conclusion, the
      results demonstrate that the mevalonate pathway leading to protein prenylation is
      important for cancer cell invasion and migration in vitro. They further suggest
      that interference with this pathway is involved in inhibition of invasion and
      migration of prostate cancer cells by the amino-BP alendronate but that the
      mechanism of clodronate inhibition is different. It is possible that BPs have
      therapeutic potential in preventing the spread of prostate cancer.

PMID- 11980673
TI  - Expression of several genes in the human chromosome 3p21.3 homozygous deletion
      region by an adenovirus vector results in tumor suppressor activities in vitro
      and in vivo.
AB  - A group of candidate tumor suppressor genes (designated CACNA2D2, PL6, 101F6,
      NPRL2, BLU, RASSF1, FUS1, HYAL2, and HYAL1) has been identified in a 120-kb
      critical tumor homozygous deletion region (found in lung and breast cancers) of
      human chromosome 3p21.3. We studied the effects of six of these 3p21.3 genes
      (101F6, NPRL2, BLU, FUS1, HYAL2, and HYAL1) on tumor cell proliferation and
      apoptosis in human lung cancer cells by recombinant adenovirus-mediated gene
      transfer in vitro and in vivo. We found that forced expression of wild-type FUS1,
      101F6, and NPRL2 genes significantly inhibited tumor cell growth by induction of
      apoptosis and alteration of cell cycle processes in 3p21.3 120-kb region
      deficient (homozygous) H1299 and A549 cells but not in the 3p21.3 120-kb region
      heterozygous H358 and the normal human bronchial epithelial cells. Intratumoral
      injection of Ad-101F6, Ad-FUS1, Ad-NPRL2, and Ad-HYAL2 vectors or systemic
      administration of protamine-complexed vectors significantly suppressed growth of
      H1299 and A549 tumor xenografts and inhibited A549 experimental lung metastases
      in nu/nu mice. Together, our results, coupled with other studies demonstrating a
      tumor suppressor role for the RASSSF1A isoform, suggest that multiple contiguous
      genes in the 3p21.3 120-kb chromosomal region may exhibit tumor suppressor
      activity in vitro and in vivo.

PMID- 11980674
TI  - Mechanisms controlling cell cycle arrest and induction of apoptosis after 12
      lipoxygenase inhibition in prostate cancer cells.
AB  - Extensive studies have implicated the role of dietary fatty acids in
      prostatecancer progression. Platelet-type 12-Lipoxygenase (12-LOX) has beenshown
      to regulate growth, metastasis, and angiogenesis of prostate cancer. The effect
      of two 12-LOX inhibitors, Baicalein and N-benzyl-N-hydroxy-5-phenylpentamide
      (BHPP), on the mechanisms controlling cell cycle progression and apoptosis were
      examined in two prostate cancer cell lines, PC3 and DU-145. Treatment with
      Baicalein or BHPP resulted in a dose-dependent decrease in cell proliferation, as
      measured by BrdUrd incorporation. This growth arrest was shown to be because of
      cell cycle inhibition at G0/G1, and was associated with suppression of cyclin D1
      and D3 protein levels. PC3 cells also showed a strong decrease in phosphorylated
      retinoblastoma (pRB) protein, whereas the other retinoblastoma-associated
      proteins, p107 and p130, were inhibited in DU-145 cells. Treatment with 12
      hydroxyeicosatetraenoic acid in the presence of Baicalein blocked loss of pRB,
      whereas 12(S)-HETE alone induced pRB expression. Treatment with either Baicalein
      or BHPP resulted in significant apoptosis in both cell lines as measured by
      terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. DU-145
      cells underwent apoptosis more rapidly than PC-3 cells. The mechanisms involved
      were decreased phosphorylation of Akt, loss of survivin and subsequent activation
      of caspase-3 and caspase-7 in each cell line, decreased Bcl-2 and Bcl-X(L)
      expression in DU-145, and a shift in Bcl-2/Bax levels favoring apoptosis in PC-3
      cells. Addition of 12(S)-HETE protected both cell lines from Baicalein-induced
      apoptosis, whereas other LOX metabolites, 5(S)-HETE, or 15(S)-HETE did not. These
      results show that the 12-LOX pathway is a critical regulator of prostate cancer
      progression and apoptosis, by affecting various proteins regulating these
      processes. Therefore, inhibition of 12-LOX is a potential therapeutic agent in
      the treatment of prostate cancer.

PMID- 11980676
TI  - Do increased proinsulin concentrations explain the excess risk of coronary heart
      disease in diabetic and prediabetic subjects?

PMID- 11980677
TI  - Mouse model for atherosclerotic plaque rupture.

PMID- 11980678
TI  - Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial
      vascular endothelial growth factor 2 gene transfer by catheter delivery in
      patients with chronic myocardial ischemia.
AB  - BACKGROUND: This phase 1/2 study investigated the safety of percutaneous catheter
      based gene transfer of naked plasmid DNA encoding for vascular endothelial growth
      factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective,
      randomized, double-blind, placebo-controlled, dose-escalating study of inoperable
      patients with class III or IV angina. METHODS AND RESULTS: A steerable
      deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced
      percutaneously to the endocardial surface of the LV in 19 patients (age, 61+/-2
      years) with chronic myocardial ischemia who were not candidates for conventional
      revascularization. Patients were randomized in a double-blind fashion to receive
      6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 microg
      (n=9), 800 microg (n=9), or 2000 microg (n=1) guided by LV electromechanical
      (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections
      were delivered and caused no hemodynamic alterations, sustained ventricular
      arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point
      analysis at 12 weeks disclosed a statistically significant improvement in
      Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus
      placebo-treated patients (-1.3 versus -0.1, P=0.04). Remaining efficacy end
      points--including change in exercise duration (91.8 versus 3.9 seconds),
      functional improvement by > or =2 CCS classes (9 of 12 versus 1 of 6), and
      Seattle Angina Questionnaire data--all showed strong trends favoring efficacy of
      phVEGF2 versus placebo treatment. CONCLUSIONS: This phase 1/2, double-blind,
      randomized trial provides preliminary data that support safety of phVEGF2
      catheter-mediated myocardial gene transfer. The statistically significant
      reduction in anginal class and strong positive trends for remaining end points
      suggest that a larger phase 2/3 trial is warranted.

PMID- 11980679
TI  - Elevated C-reactive protein values and atherosclerosis in sudden coronary death:
      association with different pathologies.
AB  - BACKGROUND: Elevations in serum C-reactive protein measured by high-sensitivity
      assay (hs-CRP) have been associated with unstable coronary syndromes. There have
      been no autopsy studies correlating hs-CRP to fatal coronary artery disease.
      METHODS AND RESULTS: Postmortem sera from 302 autopsies of men and women without
      inflammatory conditions other than atherosclerosis were assayed for hs-CRP. There
      were 73 sudden deaths attributable to atherothrombi, 71 sudden coronary deaths
      with stable plaque, and 158 control cases (unnatural sudden deaths and noncardiac
      natural deaths without conditions known to elevate CRP). Atherothrombi were
      classified as plaque ruptures (n=55) and plaque erosion (n=18); plaque burden was
      estimated in each heart. Total cholesterol, high-density lipoprotein cholesterol,
      diabetes, smoking history, and body mass index were also determined.
      Immunohistochemical stains for CRP and numbers of thin cap atheromas per heart
      were quantitated in coronary deaths with hs-CRP in the highest and lowest
      quintiles. The median hs-CRP was 3.2 microg/mL in acute rupture, 2.9 microg/mL in
      plaque erosion, 2.5 microg/mL in stable plaque, and 1.4 microg/mL in controls.
      Mean log hs-CRP was higher in rupture (P<0.0001), erosion (P=0.005), and stable
      plaque (P=0.0003) versus controls. By multivariate analysis, atherothrombi
      (P=0.02), stable plaque (P=0.003), and plaque burden (P=0.03) were associated
      with log hs-CRP independent of age, sex, smoking, and body mass index. Mean
      staining intensity for CRP of macrophages and lipid core in plaques was
      significantly greater in cases with high hs-CRP than those with low CRP
      (P=0.0001), as were mean numbers of thin cap atheromas (P<0.0001). CONCLUSIONS:
      hs-CRP is significantly elevated in patients dying suddenly with severe coronary
      artery disease, both with and without acute coronary thrombosis, and correlates
      with immunohistochemical staining intensity and numbers of thin cap atheroma.

PMID- 11980680
TI  - Enhanced activity of variant phospholipase C-delta1 protein (R257H) detected in
      patients with coronary artery spasm.
AB  - BACKGROUND: We recently demonstrated that phospholipase C (PLC)-delta1 activity
      in cultured skin fibroblasts obtained from patients with coronary spastic angina
      (CSA) is enhanced. We tested the hypothesis that structural abnormality in PLC
      delta1 isoform is a cause of the enhanced activity. METHODS AND RESULTS: Sequence
      analysis of the cDNA coding for PLC-delta1 obtained from fibroblasts revealed
      that one conversion of guanine to adenine (A) was present at nucleotide position
      864 in one CSA patient, resulting in the amino acid replacement of arginine 257
      by histidine (R257H). The incidence of 864A/A in genomic DNA, analyzed by single
      strand conformation polymorphism, was greater in patients with CSA than in male
      control subjects (6 of 57 patients with CSA versus 1 of 62 control subjects,
      P<0.05). The activity of the variant PLC-delta1 protein under free calcium
      concentration between 10(-8) and 10(-7) mol/L was 2-fold higher than that of the
      wild-type protein. Baseline intracellular calcium concentration ([Ca2+]i) in
      human embryonic kidney 293 cells transfected with the variant PLC-delta1 was
      higher than that in cells with the wild type. The peak increase in [Ca2+]i in
      response to acetylcholine at 10(-6) and 10(-5) mol/L was greater in the cells
      with the variant PLC-delta1 than in those with the wild type. CONCLUSIONS: These
      findings indicate that the R257H variant in the PLC-delta1 gene detected in
      patients with CSA is associated with enhancement of enzyme activity, and they
      describe a novel mechanism for the enhanced coronary vasomotility in CSA.

PMID- 11980681
TI  - NADPH oxidase mediates tissue factor-dependent surface procoagulant activity by
      thrombin in human vascular smooth muscle cells.
AB  - BACKGROUND: Tissue factor (TF) initiates the extrinsic coagulation cascade
      leading to thrombin formation. Thrombin induces TF mRNA in vascular smooth muscle
      cells (VSMCs), thereby contributing to the prolonged procoagulant activity and
      enhanced thrombogenicity at sites of vascular injury. However, the signaling
      mechanisms mediating this thrombogenic cycle are unclear. Characteristically,
      vascular injury promotes the generation of reactive oxygen species (ROS). Because
      ROS exert signaling functions, we investigated whether the NADPH oxidase, an
      important source of ROS in VSMCs, contributes to upregulation of TF by thrombin.
      METHODS AND RESULTS: Thrombin not only stimulated TF mRNA expression, but also TF
      dependent surface procoagulant activity in cultured human VSMCs. This response
      was attenuated by antioxidants; the flavin inhibitor diphenylene-iodonium,
      Clostridium difficile toxin B, which inhibits Rho GTPases, p22phox antisense
      oligonucleotides, or the dominant-negative RacT17N mutant. Inhibitors of p38 MAP
      kinase and phosphatidylinositol (PI) 3-kinase also prevented thrombin-stimulated
      TF mRNA expression. Furthermore, thrombin stimulated the phosphorylation of the
      PI 3-kinase target protein kinase B/Akt in a redox-sensitive and NADPH oxidase
      dependent manner. CONCLUSION: These findings indicate that the NADPH oxidase is
      essentially involved in the redox-sensitive induction of TF mRNA expression and
      surface procoagulant activity by thrombin. This response is mediated by NADPH
      oxidase-dependent activation of p38 MAP kinase and the PI 3-kinase/protein kinase
      B/Akt pathway. Given that active TF promotes thrombin formation, the NADPH
      oxidase may play a crucial role in perpetuating the thrombogenic cycle in the
      injured vessel wall.

PMID- 11980682
TI  - Incidence, morphology, angiographic findings, and outcomes of intramural
      hematomas after percutaneous coronary interventions: an intravascular ultrasound
      study.
AB  - BACKGROUND: Intramural hematomas during percutaneous coronary intervention (PCI)
      have not been well studied. METHODS AND RESULTS: We used intravascular ultrasound
      to determine the incidence, morphology, and clinical features of post-PCI
      intramural hematomas. In 905 patients with 1025 consecutive native coronary
      artery, non-in-stent restenosis lesions undergoing PCI, 72 hematomas were
      detected in 69 arteries in 68 patients. The incidence of intramural hematomas per
      artery was 6.7% (69 of 1025); 36% (26 of 72) involved the proximal reference
      artery, 18% (13 of 72) were confined to the lesion, and 46% (33 of 72) involved
      the distal reference artery. The entry site from the lumen into the hematoma was
      identified in 86% of hematomas (62 of 72) and had the appearance of a dissection
      into the media. Conversely, a re-entry site was identifiable in only 8% (6 of
      72). The axial extension of the hematoma was distal in 63% and proximal in 37%.
      In 60% of the hematomas (42 of 72) the angiogram had the appearance of a
      dissection; in 11% (8 of 72), it appeared to be a new stenosis; and in 29% (22 of
      72), no significant abnormality was detected. Non-Q-wave myocardial infarctions
      occurred in 26% of patients (17 of 65). In 3 patients, the creatine kinase-MB was
      not measured during the hospital stay. Repeat revascularization occurred in 2
      patients in-hospital, 2 additional patients at 1 month, and 8 additional patients
      at 1 year. There were 3 sudden deaths at 1 year. CONCLUSIONS: Intravascular
      ultrasound identified intramural hematomas after 6.7% of PCIs. The mechanism
      appeared to be a dissection into the media where blood accumulated because of a
      lack of re-entry. A third of ultrasound-identified hematomas showed no
      angiographic abnormalities. There was a high rate of non-Q-wave myocardial
      infarction, need for repeat revascularization, and sudden death in patients with
      hematomas.

PMID- 11980683
TI  - Efficacy and temporal stability of reduced safety margins for ventricular
      defibrillation: primary results from the Low Energy Safety Study (LESS).
AB  - BACKGROUND: Traditionally, a safety margin of at least 10 J between the maximum
      output of the pulse generator and the energy needed for ventricular
      defibrillation has been used because lower safety margins were associated with
      unacceptably high rates of failed defibrillation and sudden cardiac death. The
      Low Energy Safety Study (LESS) was a prospective, randomized assessment of the
      safety margin requirements for modern implantable cardioverter-defibrillator
      (ICD) systems. METHODS AND RESULTS: A total of 636 patients undergoing initial
      ICD implantation with a dual-coil lead and active pulse generator were evaluated.
      The defibrillation threshold (DFT) and enhanced DFT (DFT+ and DFT++) were
      measured using a modified step-down protocol. Conversion testing of induced
      ventricular fibrillation before discharge, at 3 months, and at 12 months was
      performed, as was randomization to chronic programming at either 2 steps above
      DFT++ or maximal output. The induced ventricular fibrillation data had conversion
      success rates of 91.4%, 97.9%, 99.1%, 99.6%, and 99.8% for safety margins of 0,
      1, 2, 3, and 4 steps above the DFT++, respectively. A margin of 4 to 6 J was
      adequate to maintain high conversion success over time (98.9% before discharge
      versus 99.2% at 12 months; P=NS). Over a mean follow-up of 24+/-13 months,
      conversion of spontaneously occurring ventricular tachyarrhythmias >200 bpm was
      identical (97.3%), despite a safety margin difference of 5.2+/-1.1 J for the 2
      step group versus 20.8+/-4.2 J for maximal output. CONCLUSIONS: With a rigorous
      implantation algorithm, a safety margin of about 5 J is adequate for safe
      implantation of modern ICD systems.

PMID- 11980684
TI  - Cost-effectiveness of the implantable cardioverter-defibrillator versus
      antiarrhythmic drugs in survivors of serious ventricular tachyarrhythmias:
      results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) economic
      analysis substudy.
AB  - BACKGROUND: The implantable cardioverter-defibrillator (ICD) is an effective but
      expensive device. We used prospectively collected data from a large randomized
      clinical trial of secondary prevention of life-threatening ventricular
      arrhythmias to determine the cost-effectiveness of the ICD compared with
      antiarrhythmic drug (AAD) therapy, largely with amiodarone. METHODS AND RESULTS:
      Charges for initial and repeat hospitalizations, emergency room, and day surgery
      stays and the costs of antiarrhythmic drugs were collected on 1008 patients.
      Detailed records of all other medical encounters and expenses were collected on a
      subgroup of 237 patients. Regression models were then created to attribute these
      expenses to the rest of the patients. Charges were converted to 1997 costs using
      standard methods. Costs and life years were discounted at 3% per year. Three-year
      survival data from the Antiarrhythmics Versus Implantable Defibrillators trail
      were used to calculate the base-case cost-effectiveness (C/E) ratio. Six-year,
      twenty-year, and lifetime C/E ratios were also estimated. At 3 years, total costs
      were $71 421 for a patient taking AADs and $85 522 for a patient using an ICD,
      and the ICD provided a 0.21-year survival benefit over AAD treatment. The base
      case C/E ratio was thus $66 677 per year of life saved by the ICD compared with
      AAD therapy (95% CI, $30 761 to $154 768). Six- and 20-year C/E ratios remained
      stable between $68 000 and $80 000 per year of life saved. CONCLUSIONS: The ICD
      is moderately cost-effective for secondary prevention of life-threatening
      ventricular arrhythmias, as judged from prospectively collected data in a
      randomized clinical trial.

PMID- 11980685
TI  - Ultrasonographic and biochemical markers of human fetal cardiac dysfunction in
      placental insufficiency.
AB  - BACKGROUND: Placental insufficiency may lead to fetal cardiovascular compromise.
      We sought to determine whether ultrasonographic parameters of fetal
      cardiovascular function correlate with umbilical arterial levels of biochemical
      markers of myocardial dysfunction and damage in placental insufficiency. METHODS
      AND RESULTS: In 48 fetuses with placental insufficiency, umbilical artery blood
      was obtained at delivery for assessment of N-terminal peptide of proatrial
      natriuretic peptide (NT-proANP) and cardiac troponin-T (cTnT). Group 1 fetuses
      (n=12) had normal NT-proANP and cTnT serum concentrations. Group 2 fetuses (n=25)
      showed increased NT-proANP (>1145 pmol/L) and normal cTnT values. Group 3 fetuses
      (n=11) had increased NT-proANP and cTnT (>0.10 ng/mL) levels. The
      ultrasonographic parameters of fetal cardiovascular function were compared
      between the groups. Pulsatility indices for veins of the ductus venosus, left
      hepatic vein, and inferior vena cava correlated significantly with NT-proANP
      levels. In group 3, ductus venosus, left hepatic vein, and inferior vena cava
      pulsatility indices for veins were higher (P<0.01) than in groups 1 and 2. The
      proportion of left ventricular cardiac output of combined cardiac output was
      greater (P<0.05) and that of right ventricle was smaller (P<0.05) in group 3 than
      in group 2. In group 3, tricuspid regurgitation was noted most often (P<0.05),
      and right ventricular fractional shortening was less (P<0.01) than in group 2.
      CONCLUSIONS: Pulsatility in human fetal systemic veins correlated significantly
      with the cardiac secretion of ANP. Fetuses with myocardial damage demonstrate
      increased systemic venous pressure, a change in the distribution of cardiac
      output toward the left ventricle, and a rise in right ventricular afterload.

PMID- 11980686
TI  - Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after
      adenovirus-mediated transfer of p53.
AB  - BACKGROUND: The presence of the tumor-suppressor gene p53 in advanced
      atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth
      muscle cells isolated from these plaques have fueled speculation about the role
      of p53 in lesion destabilization and plaque rupture. In this study, we describe a
      strategy to promote (thrombotic) rupture of preexisting atherosclerotic lesions
      using p53-induced lesion remodeling. METHODS AND RESULTS: Carotid atherogenesis
      was initiated in apolipoprotein E knockout mice by placement of a perivascular
      silastic collar. The resulting plaques were incubated transluminally with
      recombinant adenovirus carrying either a p53 or beta-galactosidase (lacZ)
      transgene. p53 transfection was restricted to the smooth muscle cell-rich cap of
      the plaque and led to an increase in cap cell apoptosis 1 day after transfer. p53
      overexpression resulted in a marked decrease in the cellular and extracellular
      content of the cap, reflected by a markedly reduced cap/intima ratio (0.21+/-0.04
      versus 0.46+/-0.03, P<0.001). The latter is a characteristic feature of plaque
      vulnerability to rupture, and whereas spontaneous rupture of p53-treated lesions
      was rare, it was found in 40% of cases after treatment with the vasopressor
      compound phenylephrine (P=0.003). CONCLUSIONS: We have demonstrated a potential
      role of p53-induced remodeling in atherosclerotic plaque destabilization. Being
      the first example of inducible rupture at a predefined location, this model
      offers a unique opportunity to delineate the processes that precede rupture and
      to evaluate plaque-stabilizing therapies.

PMID- 11980687
TI  - Quantification of left ventricular systolic function by tissue Doppler
      echocardiography: added value of measuring pre- and postejection velocities in
      ischemic myocardium.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) is a potentially powerful method for
      diagnosing myocardial ischemia. This study was designed to investigate how
      velocity patterns in ischemic myocardium relates to regional function, and to
      determine whether timing of velocity measurements relative to ejection and
      isovolumic phases may increase the diagnostic power of TDI. METHODS AND RESULTS:
      In 17 open-chest anesthetized dogs we measured pressures by micromanometers,
      myocardial longitudinal segment lengths by sonomicrometry, and velocities by TDI.
      Myocardial longitudinal strain rate was calculated as velocity divided by
      distance to the left ventricle apex. Moderate ischemia (left anterior descending
      coronary artery stenosis) caused parallel reductions in regional systolic
      shortening by sonomicrometry (P<0.05) and in peak systolic velocities by TDI
      (P<0.05). Severe ischemia (left anterior descending coronary artery occlusion),
      however, induced systolic lengthening by sonomicrometry (P<0.001), whereas peak
      TDI velocity during ejection remained positive (P<0.05). When velocities during
      isovolumic contraction (IVC) and isovolumic relaxation (IVR) were included, TDI
      correlated well with sonomicrometry; ie, systolic lengthening occurred
      predominantly during IVC and was evident as negative velocities (r=0.70,
      P<0.001), and postsystolic shortening during IVR (r=0.72, P<0.001) as positive
      velocities. In nonischemic myocardium peak systolic strain rates were more
      uniform than velocities. CONCLUSION: The present results indicate that peak
      ejection velocity is an inappropriate measure of function in severely ischemic
      myocardium. Dyskinetic myocardium deforms predominantly during the isovolumic
      phases, and therefore IVC and IVR velocities are better markers of function. When
      isovolumic as well as ejection velocities are measured, TDI has excellent ability
      to quantify regional myocardial dysfunction. Longitudinal strain rates are more
      uniform than velocities and may further improve the diagnostic power of TDI.

PMID- 11980688
TI  - Paradoxical reduction of fatty streak formation in mice lacking endothelial
      nitric oxide synthase.
AB  - BACKGROUND: The endothelial isoform of nitric oxide synthase (eNOS) has been
      considered to exert an antiatherosclerotic role through synthesis of NO. However,
      eNOS has been shown to generate superoxide, which could oxidize LDL and promote
      atherosclerosis. We sought to determine the role of eNOS in diet-induced fatty
      streak formation through the use of eNOS-deficient mice. METHODS AND RESULTS:
      Mice were fed an atherogenic diet containing 15% fat, 1.25% cholesterol, and 0.5%
      sodium cholate for 12 weeks, and atherosclerotic lesions at the aortic root were
      measured after oil-red O staining. Unexpectedly, eNOS-deficient mice developed
      much smaller aortic lesions than did wild-type control mice (2544+/-1107 versus
      7023+/-1569 microm2/section; P=0.03). This reduction in lesion formation could
      not be explained by changes in plasma levels of lipids and susceptibility of
      lipoproteins to oxidation. To examine whether eNOS contributed to the oxidation
      of LDL within the arterial wall, endothelial cells were isolated from the aorta
      of mice and incubated with native LDL in the absence or presence of N-Omega-nitro
      L-arginine methyl ester (L-NAME), a specific NOS inhibitor. L-NAME significantly
      inhibited LDL oxidation by endothelial cells from wild-type animals (P<0.05), but
      it had no effect on LDL oxidation by endothelial cells from eNOS-deficient mice.
      CONCLUSIONS: These data indicate that absence of eNOS-mediated LDL oxidation may
      contribute to the reduction of fatty-streak formation in eNOS-deficient mice.

PMID- 11980689
TI  - Raloxifene improves endothelial dysfunction in hypertension by reduced oxidative
      stress and enhanced nitric oxide production.
AB  - BACKGROUND: It has not been completely clarified whether selective estrogen
      receptor modulators (SERMs) such as raloxifene exert vasoprotective effects
      similar to those of estrogens. METHODS AND RESULTS: To investigate vascular
      effects of raloxifene, male spontaneously hypertensive rats were treated for 10
      weeks with either raloxifene (10 mg x kg(-1) x d(-1)) or vehicle. Raloxifene
      improved endothelium-dependent vasodilatation but had no effect on either
      endothelium-independent vasorelaxation or phenylephrine-induced vasoconstriction.
      Raloxifene treatment increased the release of NO from the vessel wall by enhanced
      expression and activity of endothelial NO synthase. Blood pressure reduction
      after bradykinin infusion was more pronounced in animals treated with SERMs. The
      production of superoxide in intact aortic segments was decreased by raloxifene
      treatment. Administration of raloxifene had no effect on the expression of the
      essential NAD(P)H oxidase subunits p22phox and nox1 in the vasculature but
      reduced the activity and expression of vascular membrane-bound rac1, a GTPase
      required for the activation of the NAD(P)H oxidase. Finally, blood pressure
      levels were significantly decreased in spontaneously hypertensive rats treated
      with raloxifene. All SERM effects were also detected in healthy age-matched
      Wistar rats. In cultured rat aortic vascular smooth muscle cells, raloxifene
      inhibited angiotensin II-induced reactive oxygen species production dependent on
      estrogen receptor activation. CONCLUSIONS: Raloxifene treatment improves
      hypertension-induced endothelial dysfunction by increased bioavailability of NO.
      This is achieved by an increased activity of endothelial NO synthase and by an
      estrogen receptor-dependent reduction in release of reactive oxygen species from
      vascular cells. These vascular effects cause a profound blood pressure reduction
      and lead to decreased vascular damage in male spontaneously hypertensive rats.

PMID- 11980690
TI  - Anisotropic conduction properties in canine atria analyzed by high-resolution
      optical mapping: preferential direction of conduction block changes from
      longitudinal to transverse with increasing age.
AB  - BACKGROUND: Anisotropic conduction properties may provide a substrate for
      reentrant arrhythmias. We investigated the age-dependent changes of structural
      and functional anisotropy in isolated right atria from infant (1 to 2 months),
      young (6 to 12 months), and old (6 to 10 years) dogs. METHODS AND RESULTS: The
      histology of the mapped atrial tissues (a small subepicardial area, 2.8x4.2 mm)
      was characterized by an age-dependent increase of myofiber width and fat cell
      infiltration between myofibers. Cx43 was distributed homogeneously over the
      entire cell surface in infant dogs, whereas it progressively polarized to the
      cell termini with increasing age. The activation sequences were analyzed by high
      resolution optical mapping using a voltage-sensitive dye. Activation fronts from
      the pacing site proceeded more rapidly along fiber orientation (longitudinal)
      than across it (transverse). Infant dogs showed "elliptical" isochrones with a
      smooth transition between longitudinal and transverse propagation, whereas old
      dogs had a "square" pattern with a sharp transition. Conduction block occurred
      predominantly during longitudinal propagation in infant dogs but during
      transverse propagation in old dogs. The shape of the wave front and the degree of
      lateral uncoupling seemed to decide the preferential direction of block. A zigzag
      activation causing an extremely slow transverse conduction was observed only in
      old dogs. CONCLUSIONS: Along with the age-dependent structural anisotropy, the
      preferential direction of block changed from longitudinal to transverse in
      association with a change in the wave front configuration. A zigzag propagation
      based on lateral uncoupling would predispose the elderly to multiple reentry and
      a higher incidence of atrial fibrillation.

PMID- 11980691
TI  - New therapeutic options in congestive heart failure: Part I.

PMID- 11980692
TI  - Is the oxidative modification hypothesis relevant to human atherosclerosis? Do
      the antioxidant trials conducted to date refute the hypothesis?

PMID- 11980693
TI  - Images in cardiovascular medicine. Radiofrequency ablation of a focal atrial
      tachycardia originating from the Marshall ligament as a trigger for atrial
      fibrillation.

PMID- 11980694
TI  - Unique features of infective endocarditis in childhood.

PMID- 11980695
TI  - Images in cardiovascular medicine. Pulmonary vein exit-block during radio
      frequency ablation of paroxysmal atrial fibrillation.

PMID- 11980696
TI  - Endothelin 1 type a receptor antagonism prevents vascular dysfunction and
      hypertension induced by 11beta-hydroxysteroid dehydrogenase inhibition: role of
      nitric oxide.

PMID- 11980697
TI  - Long-term prognostic value of coronary calcification detected by electron beam
      computed tomography in patients undergoing coronary arteriography.

PMID- 11980698
TI  - Dietary protein and weight reduction.

PMID- 11980699
TI  - On the mechanisms by which human apolipoprotein A-II gene variability relates to
      hypertriglyceridemia.

PMID- 11980702
TI  - Three-dimensional structure of the human transglutaminase 3 enzyme: binding of
      calcium ions changes structure for activation.
AB  - Transglutaminase (TGase) enzymes catalyze the formation of covalent cross-links
      between protein-bound glutamines and lysines in a calcium-dependent manner, but
      the role of Ca(2+) ions remains unclear. The TGase 3 isoform is widely expressed
      and is important for epithelial barrier formation. It is a zymogen, requiring
      proteolysis for activity. We have solved the three-dimensional structures of the
      zymogen and the activated forms at 2.2 and 2.1 A resolution, respectively, and
      examined the role of Ca(2+) ions. The zymogen binds one ion tightly that cannot
      be exchanged. Upon proteolysis, the enzyme exothermally acquires two more Ca(2+)
      ions that activate the enzyme, are exchangeable and are functionally replaceable
      by other lanthanide trivalent cations. Binding of a Ca(2+) ion at one of these
      sites opens a channel which exposes the key Trp236 and Trp327 residues that
      control substrate access to the active site. Together, these biochemical and
      structural data reveal for the first time in a TGase enzyme that Ca(2+) ions
      induce structural changes which at least in part dictate activity and, moreover,
      may confer substrate specificity.

PMID- 11980703
TI  - The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and
      ferrochelatase.
AB  - Sirohaem is a tetrapyrrole-derived prosthetic group that is required for the
      essential assimilation of sulfur and nitrogen into all living systems as part of
      the sulfite and nitrite reductase systems. The final two steps in the
      biosynthesis of sirohaem involve a beta-NAD(+)-dependent dehydrogenation of
      precorrin-2 to generate sirohydrochlorin followed by ferrochelation to yield
      sirohaem. In Saccharomyces cerevisiae, Met8p is a bifunctional enzyme that
      carries out both of these reactions. Here, we report the 2.2 A resolution crystal
      structure of Met8p, which adopts a novel fold that bears no resemblance to the
      previously determined structures of cobalt- or ferro-chelatases. Analysis of
      mutant proteins suggests that both catalytic activities share a single active
      site, and that Asp141 plays an essential role in both dehydrogenase and chelatase
      processes.

PMID- 11980704
TI  - Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA
      family.
AB  - CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of
      murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine
      coronavirus. Here we report the crystal structure of soluble murine
      sCEACAM1a[1,4], which is composed of two Ig-like domains and has MHV neutralizing
      activity. Its N-terminal domain has a uniquely folded CC' loop that encompasses
      key virus-binding residues. This is the first atomic structure of any member of
      the CEA family, and provides a prototypic architecture for functional exploration
      of CEA family members. We discuss the structural basis of virus receptor
      activities of murine CEACAM1 proteins, binding of Neisseria to human CEACAM1, and
      other homophilic and heterophilic interactions of CEA family members.

PMID- 11980705
TI  - Molecular architecture of a retinal cGMP-gated channel: the arrangement of the
      cytoplasmic domains.
AB  - Cyclic nucleotide-gated (CNG) channels play a central role in the conversion of
      sensory information, such as light and scent, into primary electrical signals. We
      have purified the CNG channel from bovine retina and have studied it using
      electron microscopy and image processing. We present the structure of the channel
      to 35 A resolution. This three-dimensional reconstruction provides insight into
      the architecture of the protein, suggesting that the cyclic nucleotide-binding
      domains, which initiate the response to ligand, 'hang' below the pore-forming
      part of the channel, attached by narrow linkers. The structure also suggests that
      the four cyclic nucleotide-binding domains present in each channel form two
      distinct domains, lending structural weight to the suggestion that the four
      subunits of the CNG channels are arranged as a pair of dimers.

PMID- 11980706
TI  - The complex of Arl2-GTP and PDE delta: from structure to function.
AB  - Arf-like (Arl) proteins are close relatives of the Arf regulators of vesicular
      transport, but their function is unknown. Here, we present the crystal structure
      of full-length Arl2-GTP in complex with its effector PDE delta solved in two
      crystal forms (Protein Data Bank codes 1KSG, 1KSH and 1KSJ). Arl2 shows a
      dramatic conformational change from the GDP-bound form, which suggests that it is
      reversibly membrane associated. PDE delta is structurally closely related to
      RhoGDI and contains a deep empty hydrophobic pocket. Further experiments show
      that H-Ras, Rheb, Rho6 and G alpha(i1) interact with PDE delta and that, at least
      for H-Ras, the intact C-terminus is required. We suggest PDE delta to be a
      specific soluble transport factor for certain prenylated proteins and Arl2-GTP a
      regulator of PDE delta-mediated transport.

PMID- 11980707
TI  - A polytopic membrane protein displays a reversible topology dependent on membrane
      lipid composition.
AB  - To address the role of phospholipids in the topological organization of polytopic
      membrane proteins, the function and assembly of lactose permease (LacY) was
      studied in mutants of Escherichia coli lacking phosphatidylethanolamine (PE). PE
      is required for the proper conformation and active transport function of LacY.
      The N-terminal half of LacY assembled in PE-lacking cells adopts an inverted
      topology in which normally non-translocated domains are translocated and vice
      versa. Post-assembly synthesis of PE triggers a conformational change, resulting
      in a lipid-dependent recovery of normal conformation and topology of at least one
      LacY subdomain accompanied by restoration of active transport. These results
      demonstrate that membrane protein topology once attained can be changed in a
      reversible manner in response to alterations in phospholipid composition, and may
      be subject to post-assembly proofreading to correct misfolded structures.

PMID- 11980708
TI  - Structure of apo-phosphatidylinositol transfer protein alpha provides insight
      into membrane association.
AB  - Phosphatidylinositol transfer protein alpha (PITP alpha) is a ubiquitous and
      highly conserved protein in multicellular eukaryotes that catalyzes the exchange
      of phospholipids between membranes in vitro and participates in cellular
      phospholipid metabolism, signal transduction and vesicular trafficking in vivo.
      Here we report the three-dimensional crystal structure of a phospholipid-free
      mouse PITP alpha at 2.0 A resolution. The structure reveals an open conformation
      characterized by a channel running through the protein. The channel is created by
      opening the phospholipid-binding cavity on one side by displacement of the C
      terminal region and a hydrophobic lipid exchange loop, and on the other side by
      flattening of the central beta-sheet. The relaxed conformation is stabilized at
      the proposed membrane association site by hydrophobic interactions with a
      crystallographically related molecule, creating an intimate dimer. The observed
      open conformer is consistent with a membrane-bound state of PITP and suggests a
      mechanism for membrane anchoring and the presentation of phosphatidylinositol to
      kinases and phospholipases after its extraction from the membrane. Coordinates
      have been deposited in the Protein Data Bank (accession No. 1KCM).

PMID- 11980709
TI  - Export of autotransported proteins proceeds through an oligomeric ring shaped by
      C-terminal domains.
AB  - An investigation was made into the oligomerization, the ability to form pores and
      the secretion-related properties of the 45 kDa C-terminal domain of the IgA
      protease (C-IgAP) from Neisseria gonorrhoeae. This protease is the best studied
      example of the autotransporters (ATs), a large family of exoproteins from Gram
      negative bacteria that includes numerous virulence factors from human pathogens.
      These proteins contain an N-terminal passenger domain that em bodies the secreted
      polypeptide, while the C-domain inserts into the outer membrane (OM) and trans
      locates the linked N-module into the extracellular medium. Here we report that
      purified C-IgAP forms an oligomeric complex of approximately 500 kDa with a ring
      like structure containing a central cavity of approximately 2 nm diameter that is
      the conduit for the export of the N-domains. These data overcome the previous
      model for ATs, which postulated the passage of the N-module through the
      hydrophilic channel of the beta-barrel of each monomeric C-domain. Our results
      advocate a secretion mechanism not unlike other bacterial export systems, such as
      the secretins or fimbrial ushers, which rely on multimeric complexes assembled in
      the OM.

PMID- 11980710
TI  - Tetrahedral aminopeptidase: a novel large protease complex from archaea.
AB  - A dodecameric protease complex with a tetrahedral shape (TET) was isolated from
      Haloarcula marismortui, a salt-loving archaeon. The 42 kDa monomers in the
      complex are homologous to metal-binding, bacterial aminopeptidases. TET has a
      broad aminopeptidase activity and can process peptides of up to 30-35 amino acids
      in length. TET has a central cavity that is accessible through four narrow
      channels (<17 A wide) and through four wider channels (21 A wide). This
      architecture is different from that of all the proteolytic complexes described to
      date that are made up by rings or barrels with a single central channel and only
      two openings.

PMID- 11980711
TI  - N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB
      phosphorylation and alpha CaMKII mRNA polyadenylation at synapses.
AB  - Activity-dependent local translation of dendritic mRNAs is one process that
      underlies synaptic plasticity. Here, we demonstrate that several of the factors
      known to control polyadenylation-induced translation in early vertebrate
      development [cytoplasmic polyadenylation element-binding protein (CPEB), maskin,
      poly(A) polymerase, cleavage and polyadenylation specificity factor (CPSF) and
      Aurora] also reside at synaptic sites of rat hippocampal neurons. The induction
      of polyadenylation at synapses is mediated by the N-methyl-D-aspartate (NMDA)
      receptor, which transduces a signal that results in the activation of Aurora
      kinase. This kinase in turn phosphorylates CPEB, an essential RNA-binding
      protein, on a critical residue that is necessary for polyadenylation-induced
      translation. These data demonstrate a remarkable conservation of the regulatory
      machinery that controls signal-induced mRNA translation, and elucidates an axis
      connecting the NMDA receptor to localized protein synthesis at synapses.

PMID- 11980712
TI  - Toxoplasma gondii myosin A and its light chain: a fast, single-headed, plus-end
      directed motor.
AB  - Successful host cell invasion is a prerequisite for survival of the obligate
      intracellular apicomplexan parasites and establishment of infection. Toxoplasma
      gondii penetrates host cells by an active process involving its own actomyosin
      system and which is distinct from induced phagocytosis. Toxoplasma gondii myosin
      A (TgMyoA) is presumed to achieve power gliding motion and host cell penetration
      by the capping of apically released adhesins towards the rear of the parasite. We
      report here an extensive biochemical characterization of the functional TgMyoA
      motor complex. TgMyoA is anchored at the plasma membrane and binds a novel type
      of myosin light chain (TgMLC1). Despite some unusual features, the kinetic and
      mechanical properties of TgMyoA are unexpectedly similar to those of fast
      skeletal muscle myosins. Microneedle-laser trap and sliding velocity assays
      established that TgMyoA moves in unitary steps of 5.3 nm with a velocity of 5.2
      microm/s towards the plus end of actin filaments. TgMyoA is the first fast,
      single-headed myosin and fulfils all the requirements for power parasite gliding.

PMID- 11980713
TI  - JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive
      self-renewal of primary multipotential hemopoietic cells.
AB  - Defining signals that can support the self-renewal of multipotential hemopoietic
      progenitor cells (MHPCs) is pertinent to understanding leukemogenesis and may be
      relevant to developing stem cell-based therapies. Here we define a set of
      signals, JAK2 plus either c-kit or flt-3, which together can support extensive
      MHPC self-renewal. Phenotypically and functionally distinct populations of MHPCs
      were obtained, depending on which receptor tyrosine kinase, c-kit or flt-3, was
      activated. Self-renewal was abrogated in the absence of STAT5a/b, and in the
      presence of inhibitors targeting either the mitogen-activated protein kinase or
      phosphatidylinositol 3' kinase pathways. These findings suggest that a simple two
      component signal can drive MHPC self-renewal.

PMID- 11980714
TI  - Inactivation of Cdc7 kinase in mouse ES cells results in S-phase arrest and p53
      dependent cell death.
AB  - Cdc7-related kinases play essential roles in the initiation of yeast DNA
      replication. We show that mice lacking murine homologs of Cdc7 (muCdc7) genes die
      between E3.5 and E6.5. We have established a mutant embryonic stem (ES) cell line
      lacking the muCdc7 genes in the presence of a loxP-flanked transgene expressing
      muCdc7 cDNA. Upon removal of the transgene by Cre recombinase, mutant ES cells
      cease DNA synthesis, arresting growth with S-phase DNA content, and generate
      nuclear Rad51 foci, followed by cell death with concomitant increase in p53
      protein levels. Inhibition of p53 leads to partial rescue of muCdc7(-/-) ES cells
      from cell death. muCdc7(-/-)p53(-/-) embryos survive up to E8.5, and their
      blastocysts generate inner cell mass of a significant size in vitro, whereas
      those of the muCdc7(-/-)p53(+/-) embryos undergoes complete degeneration. These
      results demonstrate that, in contrast to cell cycle arrest at the G(1)/S boundary
      observed in yeasts, loss of Cdc7 in ES cells results in rapid cessation of DNA
      synthesis within S phase, triggering checkpoint responses leading to
      recombinational repair and p53-dependent cell death.

PMID- 11980715
TI  - Inhibition of p21-mediated ROS accumulation can rescue p21-induced senescence.
AB  - The cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1/Sdi1) was identified
      initially as a gene induced in senescent cells and itself has been shown to cause
      permanent growth arrest/senescence. Reactive oxygen species (ROS), a byproduct of
      oxidative processes, can also induce an irreversible growth arrest similar to
      senescence. Here we show that p21 increased intracellular levels of ROS both in
      normal fibroblasts and in p53-negative cancer cells. N-acetyl-L-cysteine, an ROS
      inhibitor, rescued p21-induced senescence, showing that ROS elevation is
      necessary for induction of the permanent growth arrest phenotype. p16(Ink4a), a
      CDK4- and CDK6-specific inhibitor, failed to increase ROS levels, and cell cycle
      arrest induced by p16 was reversible following its down-regulation, demonstrating
      the specificity of this p21 effect. A p21 mutant that lacked the ability to bind
      proliferating cell nuclear antigen (PCNA) retained the ability to induce both ROS
      and permanent growth arrest. All of these findings establish that p21 mediates
      senescence by a mechanism involving ROS accumulation which does not require
      either its PCNA binding or the CDK inhibitory functions shared with p16.

PMID- 11980716
TI  - Unrestrained caspase-dependent cell death caused by loss of Diap1 function
      requires the Drosophila Apaf-1 homolog, Dark.
AB  - In mammals and Drosophila, apoptotic caspases are under positive control via the
      CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of apoptosis
      proteins). However, the in vivo genetic relationship between these opposing
      regulators is not known. In this study, we demonstrate that a dark mutation
      reverses catastrophic defects seen in Diap1 mutants and rescues cells specified
      for Diap1- regulated cell death in development and in response to genotoxic
      stress. We also find that dark function is required for hyperactivation of
      caspases which occurs in the absence of Diap1. Since the action of dark is
      epistatic to that of Diap1, these findings demonstrate that caspase-dependent
      cell death requires concurrent positive input through Apaf-1-like proteins
      together with disruption of IAP-caspase complexes.

PMID- 11980717
TI  - tcBid promotes Ca(2+) signal propagation to the mitochondria: control of Ca(2+)
      permeation through the outer mitochondrial membrane.
AB  - Calcium spikes established by IP(3) receptor-mediated Ca(2+) release from the
      endoplasmic reticulum (ER) are transmitted effectively to the mitochondria,
      utilizing local Ca(2+) interactions between closely associated subdomains of the
      ER and mitochondria. Since the outer mitochondrial membrane (OMM) has been
      thought to be freely permeable to Ca(2+), investigations have focused on IP(3)
      driven Ca(2+) transport through the inner mitochondrial membrane (IMM). Here we
      demonstrate that selective permeabilization of the OMM by tcBid, a proapoptotic
      protein, results in an increase in the magnitude of the IP(3)-induced
      mitochondrial [Ca(2+)] signal. This effect of tcBid was due to promotion of
      activation of Ca(2+) uptake sites in the IMM and, in turn, to facilitation of
      mitochondrial Ca(2+) uptake. In contrast, tcBid failed to control the delivery of
      sustained and global Ca(2+) signals to the mitochondria. Thus, our data support a
      novel model that Ca(2+) permeability of the OMM at the ER- mitochondrial
      interface is an important determinant of local Ca(2+) signalling. Facilitation of
      Ca(2+) delivery to the mitochondria by tcBid may also support recruitment of
      mitochondria to the cell death machinery.

PMID- 11980718
TI  - Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically
      short telomeres.
AB  - Here we analyze the functional interaction between Ku86 and telomerase at the
      mammalian telomere by studying mice deficient for both proteins. We show that
      absence of Ku86 prevents the end-to-end chromosomal fusions that result from
      critical telomere shortening in telomerase-deficient mice. In addition, Ku86
      deficiency rescues the male early germ cell apoptosis triggered by short
      telomeres in these mice. Together, these findings define a role for Ku86 in
      mediating chromosomal instability and apoptosis triggered by short telomeres. In
      addition, we show here that Ku86 deficiency results in telomerase-dependent
      telomere elongation and in the fusion of random pairs of chromosomes in
      telomerase-proficient cells, suggesting a model in which Ku86 keeps normal-length
      telomeres less accessible to telomerase-mediated telomere lengthening and to DNA
      repair activities.

PMID- 11980719
TI  - Spi-B can functionally replace PU.1 in myeloid but not lymphoid development.
AB  - Mature macrophages, neutrophils and lymphoid cells do not develop in PU.1(-/-)
      mice. In contrast, mice lacking the highly related protein Spi-B generate all
      hematopoietic lineages but display a B-cell receptor signaling defect. These
      distinct phenotypes could result from functional differences between PU.1 and Spi
      B or their unique temporal and tissue-specific expression (PU.1: myeloid and B
      cells; Spi-B: B cells only). To address this question, we introduced the Spi-B
      cDNA into the murine PU.1 locus by homologous recombination. In the absence of
      PU.1, Spi-B rescued macrophage and granulocyte development when assayed by in
      vitro differentiation of embryonic stem cells. Adherent, CD11b(+)/F4/80(+) cells
      capable of phagocytosis were detected in PU.1(Spi-B/Spi-B) embryoid bodies, and
      myeloid colonies were present in hematopoietic progenitor assays. Despite its
      ability to rescue myeloid differentiation, Spi-B did not rescue lymphoid
      development in a RAG-2(-/-) complementation assay. These results demonstrate an
      important difference between PU.1 and Spi-B. Careful comparison of these Ets
      factors will delineate important functional domains of PU.1 involved in
      lymphocyte lineage commitment and/or maturation.

PMID- 11980720
TI  - WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci.
AB  - The Williams Syndrome Transcription Factor (WSTF), the product of the WBSCR9
      gene, is invariably deleted in the haploinsufficiency Williams-Beuren Syndrome.
      Along with the nucleosome-dependent ATPase ISWI, WSTF forms a novel chromatin
      remodeling complex, WICH (WSTF-ISWI chromatin remodeling complex), which is
      conserved in vertebrates. The WICH complex was purified to homogeneity from
      Xenopus egg extract and was found to contain only WSTF and ISWI. In mouse cells,
      WSTF interacts with the SNF2H isoform of ISWI. WSTF accumulates in pericentric
      heterochromatin coincident with the replication of these structures, suggesting a
      role for WSTF in the replication of heterochromatin. Such a role is supported by
      the in vitro activity of both the mouse and frog WICH complexes: they are
      involved in the assembly of regular spaced nucleosomal arrays. In contrast to the
      related ISWI-interacting protein ACF1/WCRF180, WSTF binds stably to mitotic
      chromosomes. As dysfunction of other chromatin remodeling factors often has
      severe effects on development, haploinsufficiency of WSTF may explain some of the
      phenotypes associated with this disease.

PMID- 11980721
TI  - Structural basis of VDR-DNA interactions on direct repeat response elements.
AB  - The vitamin D receptor (VDR) forms homo- or heterodimers on response elements
      composed of two hexameric half-sites separated by 3 bp of spacer DNA. We describe
      here the crystal structures at 2.7-2.8 A resolution of the VDR DNA-binding region
      (DBD) in complex with response elements from three different promoters:
      osteopontin (SPP), canonical DR3 and osteocalcin (OC). These structures reveal
      the chemical basis for the increased affinity of VDR for the SPP response
      element, and for the poor stability of the VDR-OC complex, relative to the
      canonical DR3 response element. The homodimeric protein-protein interface is
      stabilized by van der Waals interactions and is predominantly non-polar. An
      extensive alpha-helix at the C-terminal end of the VDR DBD resembles that found
      in the thyroid hormone receptor (TR), and suggests a mechanism by which VDR and
      TR discriminate among response elements. Selective structure-based mutations in
      the asymmetric homodimeric interface result in a VDR DBD protein that is
      defective in homodimerization but now forms heterodimers with the 9-cis retinoic
      acid receptor (RXR) DBD.

PMID- 11980722
TI  - Evidence for a polynuclear metal ion binding site in the catalytic domain of
      ribonuclease P RNA.
AB  - Interactions with divalent metal ions are essential for the folding and function
      of the catalytic RNA component of the tRNA processing enzyme ribonuclease P
      (RNase P RNA). However, the number and location of specific metal ion
      interactions in this large, highly structured RNA are poorly understood. Using
      atomic mutagenesis and quantitative analysis of thiophilic metal ion rescue we
      provide evidence for metal ion interactions at the pro-R(P) and pro-S(P) non
      bridging phosphate oxygens at nucleotide A67 in the universally conserved helix
      P4. Moreover, second-site modifications within helix P4 and the adjacent single
      stranded region (J3/4) provide the first evidence for metal ion interactions with
      nucleotide base functional groups in RNase P RNA and reveal the presence of an
      additional metal ion important for catalytic function. Together, these data are
      consistent with a cluster of metal ion interactions in the P1-P4 multi-helix
      junction that defines the catalytic core of the RNase P ribozyme.

PMID- 11980723
TI  - Two novel phosphorylation sites on FKHR that are critical for its nuclear
      exclusion.
AB  - FKHR is phosphorylated by protein kinase B (PKB) at Thr24, Ser256 and Ser319 in
      response to growth factors, stimulating the nuclear exit and inactivation of this
      transcription factor. Here we identify two further residues, Ser322 and Ser325,
      that become phosphorylated in insulin-like growth factor-1 (IGF-1)-stimulated
      cells and which are mediated by the phosphatidylinositol 3-kinase-dependent PKB
      catalysed phosphorylation of Ser319. Phosphorylation of Ser319 forms a consensus
      sequence for phosphorylation by CK1, allowing it to phosphorylate Ser322, which
      in turn primes the CK1-catalysed phosphorylation of Ser325. IGF-1 stimulates the
      phosphorylation of Thr24, Ser256, Ser319, Ser322 and Ser325 in embryonic stem
      (ES) cells, but not in PDK1-/- ES cells, providing genetic evidence that PDK1
      (the upstream activator of PKB) is required for the phosphorylation of FKHR in
      mammalian cells. In contrast, the phosphorylation of Ser329 is unaffected by IGF
      1 and the phosphorylation of this site is not decreased in PDK1-/- ES cells. The
      cluster of phosphorylation sites at Ser319, Ser322, Ser325 and Ser329 appears to
      accelerate nuclear export by controlling the interaction of FKHR with the Ran
      containing protein complex that mediates this process.

PMID- 11980724
TI  - Post-termination complex disassembly by ribosome recycling factor, a functional
      tRNA mimic.
AB  - Ribosome recycling factor (RRF) together with elongation factor G (EF-G)
      disassembles the post- termination ribosomal complex. Inhibitors of
      translocation, thiostrepton, viomycin and aminoglycosides, inhibited the release
      of tRNA and mRNA from the post-termination complex. In contrast, fusidic acid and
      a GTP analog that fix EF-G to the ribosome, allowing one round of tRNA
      translocation, inhibited mRNA but not tRNA release from the complex. The release
      of tRNA is a prerequisite for mRNA release but partially takes place with EF-G
      alone. The data are consistent with the notion that RRF binds to the A-site and
      is translocated to the P-site, releasing deacylated tRNA from the P- and E-sites.
      The final step, the release of mRNA, is accompanied by the release of RRF and EF
      G from the ribosome. With the model post-termination complex, 70S ribosomes were
      released from the post-termination complex by the RRF reaction and were then
      dissociated into subunits by IF3.

PMID- 11980725
TI  - Directional bias during mating type switching in Saccharomyces is independent of
      chromosomal architecture.
AB  - Haploid Saccharomyces cells have the remarkable potential to change mating type
      as often as every generation, a process accomplished by an intrachromosomal gene
      conversion between an expressor locus MAT and one of two repositories of mating
      type information, HML or HMR. The particular locus selected as donor is dictated
      by the mating type of the cell, a bias that ensures productive mating type
      interconversion. Here we use green fluorescent protein tagging of the expressor
      and donor loci on chromosome III to show that this preference for donor locus
      does not result from a predetermined organization of chromosome III: HML and MAT
      as well as HMR and MAT remain separated in cells of both mating types. In fact,
      cells in which the inappropriate donor locus is artificially tethered to MAT
      still predominantly select the correct donor. We find, though, that initiation of
      switching leads to a rapid association of the correct donor locus with MAT. Thus,
      in mating type switching in Saccharomyces, donor preference is imposed at
      commitment to recombination rather than at physical contact of interacting DNA
      strands.

PMID- 11980726
TI  - Phosphorylation of cucumber mosaic virus RNA polymerase 2a protein inhibits
      formation of replicase complex.
AB  - The 2a (polymerase) protein of cucumber mosaic virus (CMV) was shown to be
      phosphorylated both in vivo and in vitro. In vitro assays using 2a protein
      mutants and tobacco protein kinases showed that the 2a protein has at least three
      phosphorylation sites, one of which is located within the N-terminal 126 amino
      acid region. This region is essential and sufficient for interaction with the CMV
      1a protein. When phosphorylated in vitro, the 2a protein N-terminal region failed
      to interact with the 1a protein. Since the 1a-2a interaction is essential for the
      replication of CMV, this suggests that phosphorylation of the N-terminal region
      of the 2a protein negatively modulates the interaction in vivo, and may have a
      regulatory role acting directly in viral infection.

PMID- 11980727
TI  - The children of assisted reproduction--the need for an ongoing debate.

PMID- 11980728
TI  - What is the optimal medical management of infertility and minor endometriosis?
      Analysis and future prospects.
AB  - By asking the question 'What is the optimal medical management of infertility and
      minor endometriosis?', it is assumed that endometriosis has a detrimental effect
      on fertility. The published data suggest that oocyte dysfunction may contribute
      to infertility associated with endometriosis. This is expressed as a reduction in
      fertilization and implantation rates; implantation rates to a lesser extent,
      though still significant. Other evidence for oocyte dysfunction exists, not all
      of which is consistent. Suppression of ovulation and menstruation to treat
      endometriosis-associated infertility is not effective. However, ovulation
      induction, perhaps with intrauterine insemination, does result in pregnancy rates
      higher than in control cycles, while stimulated IVF success rates are equivalent
      to those of other diagnostic groups. For the future, angiogenesis is critical to
      the support of endometriotic deposits and targeted therapies are promised; their
      role in improving fertility has not yet been explored.

PMID- 11980729
TI  - Why does hydrosalpinx reduce fertility? The importance of hydrosalpinx fluid.
AB  - The debate on hydrosalpinx and impaired IVF outcome has mainly focused on the
      best treatment before IVF and on functional surgery as an alternative treatment.
      We would like to initiate a debate on the possible reasons why the outcome is
      impaired. We know that salpingectomy is effective in terms of improved birth
      rates after IVF, but we do not know exactly why. The main focus is on embryotoxic
      properties of the hydrosalpinx fluid, which include micro-organisms, endotoxins,
      cytokines, oxidative stress and lack of nutrients. The endometrial receptivity
      may be reduced as an effect of disturbed expression of the cytokine cascade,
      which is essential for implantation. The presence of excessive fluid in the
      uterine cavity may also be a mechanical hindrance to implantation. We believe
      that the hydrosalpinx fluid is of crucial importance, but the actual mechanism of
      action needs to be clarified.

PMID- 11980730
TI  - Aspirin dilemma. Remodelling the hypothesis from a fertility perspective.
AB  - Many clinical trials in obstetrics have failed to demonstrate improved outcomes
      with low-dose aspirin. This is not entirely surprising as prescribing aspirin for
      compromised tissue perfusion without insight into underlying pathology inevitably
      leads to suboptimal outcomes. We argue that a mismatch between the aspirin dose
      and the underlying pathology of altered tissue perfusion is the key factor to
      this failure. Based on this groundwork, we address the question of how best to
      optimize the dose of aspirin for use in fertility management, by providing
      examples from the assisted conception and recurrent miscarriage settings.

PMID- 11980731
TI  - Optimizing the embryo transfer technique.
AB  - The technique of embryo transfer is very crucial and great attention and time
      should be given to this step. In order to optimize the embryo transfer technique,
      several precautions should be taken. The first and most important is to avoid the
      initiation of uterine contractility. This can be achieved by the use of soft
      catheters, gentle manipulation and by avoiding touching the fundus. Secondly,
      proper evaluation of the uterine cavity and utero-cervical angulation is very
      important, and can be achieved by performing dummy embryo transfer and by
      ultrasound evaluation of the utero-cervical angulation and uterine cavity length.
      Another important step is the removal of cervical mucus so that it does not stick
      to the catheter and inadvertently remove the embryo during catheter withdrawal.
      Finally, one has to be absolutely sure that the embryo transfer catheter has
      passed the internal cervical os and that the embryos are delivered gently inside
      the uterine cavity.

PMID- 11980732
TI  - Lack of submicroscopic rearrangements involving telomeres in reproductive
      failures.
AB  - BACKGROUND: It has been recognized that chromosomal abnormalities are one of the
      most important causes of the high mortality rate in human concepti. Among these
      abnormalities, the unbalanced transmission of a parental chromosomal
      rearrangement is frequently observed, and couples with a history of pregnancy
      losses are therefore referred for genetic counselling and to establish their
      karyotype. Unbalanced chromosomal rearrangements involving telomeres are emerging
      as an important cause of mental retardation and/or congenital malformations in
      humans. As suggested by several authors, they could also be responsible for
      recurrent miscarriages. The aim of this study was to screen cryptic chromosome
      abnormalities in couples referred to our laboratory for recurrent unexplained
      miscarriages. METHODS AND RESULTS: Karyotyping was performed in 57 couples (114
      patients). A detectable chromosomal abnormality was diagnosed in seven cases,
      thus limiting the analysis of telomeres to only 100 patients. Two different
      protocols were used according to the number of metaphases on slides. No telomeric
      chromosome abnormality was detected in our study. CONCLUSION: The use of FISH
      telomeric probes is not of clinical interest in the systematic screening of
      couples with multiple miscarriages and should be performed only in those with a
      familial history of mental retardation and congenital malformations.

PMID- 11980733
TI  - Successful application of preimplantation genetic diagnosis for beta-thalassaemia
      and sickle cell anaemia in Italy.
AB  - BACKGROUND: In Italy, the autosomal recessive diseases beta-thalassaemia and
      sickle cell anaemia are so widespread that in some regions they can be defined as
      'social diseases'. In this study, nine clinical applications of preimplantation
      genetic diagnosis (PGD) were performed for beta-thalassaemia and sickle cell
      anaemia on seven Sicilian couples and carriers of beta-globin gene mutations.
      METHODS AND RESULTS: The studied mutations were: Cd39, HbS, IVS1 nt1, IVS1 nt6
      and IVS1 nt110. ICSI was performed with partner's sperm on 131 out of 147
      retrieved oocytes, and this resulted in 72 zygotes; 32 embryos were successfully
      biopsied on day 3. The biopsied blastomeres were lysed and the beta-globin
      alleles amplified by nested PCR. The mutation diagnosis was performed by
      restriction enzyme digestion and reverse dot-blot. The amplification efficacy was
      97.2%. The genotype study of non-transferred and surplus embryos showed that the
      allele drop-out rate was 8.6%. Seventeen embryos were transferred in utero on day
      4. All couples received an embryo transfer; of the four pregnancies obtained,
      three resulted in live births and one miscarried at 11 weeks. Prenatal diagnosis
      at the 11th week and miscarriage material analysis confirmed the PGD results.
      CONCLUSIONS: These studies represent the first successful application of PGD for
      beta-thalassaemia and sickle cell anaemia in Italy.

PMID- 11980734
TI  - Multiplex interphase FISH as a screen for common aneuploidies in spontaneous
      abortions.
AB  - BACKGROUND: A multiplex fluorescence in-situ hybridization (FISH) strategy using
      chromosome-specific probes for eight chromosomes as an initial screen for
      chromosome abnormalities in uncultured tissues from spontaneous abortions was
      evaluated. METHODS: Fifty-seven prefetal spontaneous abortions were studied by
      karyotyping cultured cells and using FISH on uncultured cells. Two probe sets
      were used, identifying chromosomes 13, 15, 16, 18, 21, 22, X and Y. RESULTS:
      Abnormalities were detected in 53% of cases by karyotyping, and 54% of cases by
      FISH. FISH detected an abnormality in four of five cases where cultures failed,
      and in two cases where maternal cells apparently overgrew the culture. FISH
      missed four trisomies not identifiable with the probe sets, and one trisomy
      because one probe set was unscorable. FISH using these probes identified 83% of
      all abnormalities detected by karyotyping. CONCLUSIONS: FISH can detect
      abnormalities in a significant proportion of cases where the culture fails to
      grow or is contaminated by maternal cell growth. Multiplex FISH as an initial
      screen, followed by culture and karyotyping in cases where no abnormality is
      detected, would identify a higher proportion of chromosome abnormalities in
      spontaneous abortion specimens than karyotype analysis alone.

PMID- 11980735
TI  - Experimental evidence that changes in oocyte growth influence meiotic chromosome
      segregation.
AB  - BACKGROUND: It is well known that the fidelity of meiotic chromosome segregation
      is greatly reduced with increasing maternal age in humans. More recently, direct
      studies of human oocytes have demonstrated a striking age-related increase in
      oocytes exhibiting gross disturbances in chromosome alignment on the meiotic
      spindle. This abnormality, termed congression failure, has been postulated to be
      causally related to human non-disjunction and to result from subtle alterations
      in folliculogenesis that develop with advancing reproductive age. METHODS:
      Immunofluorescence staining, conventional cytogenetic analysis and spectral
      karyotyping of oocytes from mouse models were used to investigate the hypothesis
      that changes in the regulation of folliculogenesis induce meiotic defects.
      RESULTS: Mutations that affect oocyte growth were found to increase the frequency
      of congression failure at first meiotic metaphase. Importantly, increased
      congression failure was correlated with meiotic non-disjunction, suggesting a
      cause-and-effect relationship. CONCLUSIONS: Our findings support the hypothesis
      that congression failure results from disturbances in the complex interplay of
      signals regulating folliculogenesis and that these changes subtly alter the late
      stages of oocyte growth, increasing the risk of a non-disjunction error. These
      findings have important implications for human aneuploidy, since they suggest
      that it may be possible to develop prophylactic treatments for reducing the risk
      of age-related aneuploidy.

PMID- 11980736
TI  - Effects of varying gonadotrophin dose and timing on antrum formation and
      ovulation efficiency of mouse follicles in vitro.
AB  - BACKGROUND: This study tested factors affecting mouse follicle growth in vitro,
      to determine end-points marking follicle function in vitro. METHODS: Pre-antral
      follicles (mean 137 microm) from B6CBF1 mice were cultured in a substrate
      adherent system for < or = 14 days. FSH (0-1000 mIU/ml) day of HCG (1.5 IU/ml
      days 9-14) protein supplement [fetal calf serum (FCS) (x2) mouse serum (x2)
      hypogonadal (hpg) mouse serum or human serum albumin (HSA)] were varied. Follicle
      survival timing of antrum formation incidence of ovulation within 16,24,40,48 h
      of HCG oocyte growth were assessed. RESULTS: FSH (100 mIU/ml) produced the best
      antral development (P < 0.001 versus 10 and 1000 mIU/ml). Antra were observed
      from day 5. Transient antra formed occasionally in the absence of FSH. By 14 days
      significant senescence had occurred (P < 0.001) but the proportion of follicles
      ovulating within 16 h of HCG declined from day 9 onwards indicating this to be a
      more sensitive marker of follicle responsiveness. Optimal growth occurred in 5%
      FCS (x2) or hpg mouse serum although fewer follicles ovulated in hpg serum (P <
      0.05). No normal growth occurred in normal mouse serum (x2) or HSA. Oocytes grew
      to full size within 9 days with 100 mIU/ml FSH FCS. CONCLUSIONS: These data
      provide sensitive end-points for assessing follicle growth in vitro.

PMID- 11980737
TI  - Decreased tissue inhibitor of metalloproteinase in the endometrium of women using
      depot medroxyprogesterone acetate: a role for altered endometrial matrix
      metalloproteinase/tissue inhibitor of metalloproteinase balance in the
      pathogenesis of abnormal uterine bleeding?
AB  - BACKGROUND: Abnormal uterine bleeding is commonly associated with progestin-only
      contraceptives, including depot medroxyprogesterone acetate (DMPA), and remains
      the main reason why these agents are discontinued. Matrix metalloproteinases
      (MMP), enzymes which degrade specific extracellular matrix components, and
      leukocytes are implicated in menstruation. Alteration in endometrial MMP-9 and
      leukocytes has been described in users of other progestin-only contraceptives,
      suggesting a potential role in the pathogenesis of abnormal uterine bleeding.
      METHODS: This study describes the immunohistochemical localization of MMP-9, the
      tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2 and TIMP-3, and
      leukocytes [CD3+ T lymphocytes, CD68+ macrophages and CD56+ uterine natural
      killer cells (uNK cells)] in the endometrium of women using DMPA. Comparison is
      made with perimenstrual endometria from normal cycling women. RESULTS: Similar to
      the perimenstrual period, an influx of MMP-9 positive cells (identified as
      neutrophils and CD3+ T cells on the basis of dual immunofluorescence),
      macrophages and uNK cells was observed in the endometrium of DMPA users. However,
      significantly more endometrial T lymphocytes were observed in DMPA users.
      Immunoreactive TIMP, present in all endometrial compartments, demonstrated a
      significantly decreased immunostaining intensity score in endometrial epithelium
      (TIMP-1 and TIMP-2), stroma (TIMP-1, TIMP-2 and TIMP-3), endothelium (TIMP-1 and
      TIMP-2) and vascular smooth muscle (TIMP-1) of DMPA users compared with controls.
      No correlation was observed between the parameters studied and bleeding patterns
      reported by subjects. CONCLUSIONS: These findings provide additional evidence for
      the importance of the MMP/TIMP balance in the loss/maintenance of endometrial
      integrity and in the complex pathological mechanisms involved in the troubling
      side-effect of menstrual bleeding disturbance.

PMID- 11980738
TI  - Angiogenesis occurs by vessel elongation in proliferative phase human
      endometrium.
AB  - BACKGROUND: Angiogenesis occurs by at least three mechanisms: sprouting,
      intussusception and elongation. Studies to date have failed to identify the
      mechanisms or timing of endometrial angiogenesis during the menstrual cycle. The
      aim of this study was to determine if vessel elongation plays a role in human
      endometrial angiogenesis. METHODS: Forty-nine full thickness endometrial sections
      from 27 hysterectomy samples were immunostained for CD34 to identify blood
      vessels, and analysed using an interactive computerized stereological program.
      Based on counts from 9746 individual microscope fields, blood vessel length
      density (L(v)), branch point density (N(v)) and mean vessel length per branch
      point (L(v)/N(v)) were calculated for three endometrial zones during five phases
      of the menstrual cycle. RESULTS: There was an increase in L(v)/N(v) in the mid
      late proliferative compared with early proliferative, early-mid secretory and
      late secretory phases of the menstrual cycle in the functionalis (mean +/- SEM:
      174.5 +/- 20.1 versus 76.6 +/- 8.4, 118.6 +/- 9.4 and 104.2 +/- 4.1 microm
      respectively, P < 0.001) and between the mid-late proliferative and the menstrual
      phases in the basalis (158.0 +/- 18.2 versus 95.4 +/- 10.0 microm, P = 0.025). An
      increase in L(v) occurred in the subepithelial capillary plexus in the mid-late
      proliferative and early-mid secretory phases compared with the early
      proliferative phase (316.7 +/- 32.4 and 338.8 +/- 45.3 versus 178.5 +/- 8.9
      mm/mm(3), P = 0.027). CONCLUSIONS: These data are the first evidence that vessel
      elongation is a major angiogenic mechanism in mid-late proliferative phase human
      endometrium.

PMID- 11980739
TI  - The influence of body mass index, basal FSH and age on the response to
      gonadotrophin stimulation in non-polycystic ovarian syndrome patients.
AB  - BACKGROUND: Adequate ovarian response to exogenous gonadotrophins is important
      for both ovulation induction (OI) and controlled ovarian stimulation (COS). The
      objective of this study was to analyse the effect of a number of clinical factors
      that influence ovarian response in non-polycystic ovarian syndrome (non-PCOS)
      patients. METHODS: A total of 140 OI cycles (52 subjects), where each subject had
      a single abnormality (elevated FSH, abnormal body mass index (BMI) or > or = 40
      years of age), were compared with 54 cycles (15 subjects) where the patients
      displayed none of these abnormal features (the normal group). Similarly, 275 COS
      cycles (135 subjects), where each subject displayed a single abnormality, were
      compared with 79 cycles (40 subjects) in the normal group. RESULTS: For OI,
      subjects with a high basal FSH generally had an inadequate response with a poor
      chance of conception. Subjects with an abnormal BMI commonly required dosage
      adjustment so were more difficult to manage. Their potential for conception was
      normal. Older women seemed to respond normally with a normal expectation of
      conception. In the COS group, subjects with a moderately high basal FSH responded
      and conceived normally. Subjects with an abnormal BMI had an increased risk of an
      inadequate response leading to cancellation but if the response was adequate then
      the outlook was good. Older women required more gonadotrophin with a poor
      response and a low chance of conception. CONCLUSION: The results have better
      defined the anticipated responses of non-PCOS patients to gonadotrophin
      stimulation in both OI and COS.

PMID- 11980740
TI  - 'Early coasting' in patients with polycystic ovarian syndrome is consistent with
      good clinical outcome.
AB  - BACKGROUND: Coasting can be an effective strategy for the prevention of severe
      ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. However,
      OHSS may still occur in cases of excessive follicular response (i.e. >10
      follicles/ovary and serum estradiol (E(2)) concentration >3000 pg/ml).
      Furthermore, prolonged coasting may result in a reduction of the oocyte retrieval
      rate and embryo quality. This pilot study investigates the potential of
      withholding gonadotrophins at an earlier stage, with the intention of minimizing
      these risks. METHODS: Gonadotrophin injections were withheld for a fixed period
      of 3 days once the leading follicle was 15 mm, whilst continuing pituitary down
      regulation in 102 obese patients with polycystic ovarian syndrome (PCOS) in whom
      there was evidence of excessive ovarian follicular response (>10 follicles per
      ovary and serum E(2) >1500 but <3000 pg/ml). The events of ovarian stimulation,
      embryological and clinical outcomes were studied prospectively. RESULTS: The mean
      number of ampoules (75 IU per ampoule) of high purity (hp) FSH was 23.2. The mean
      serum E(2) level on coasting day 1 was 1943.7 and 2169.2 pg/ml on the day of HCG
      administration. Normal fertilization and cleavage rates were obtained despite
      early withdrawal of hpFSH in the obese PCOS patients, being 73.9 and 87.7%
      respectively. The clinical pregnancy rate was 45.1%. There were no cases of
      severe OHSS. Four patients suffered pregnancy-associated late-onset moderate
      OHSS. CONCLUSIONS: This pilot study suggests that withholding gonadotrophins at
      an earlier stage in patients with excessive ovarian follicular response at
      anticipated risk of developing severe OHSS in the course of ovarian stimulation
      is consistent with good embryological and clinical outcome in IVF and ICSI
      treatment cycles.

PMID- 11980741
TI  - Value of measuring serum FSH in addition to serum estradiol in a coasting
      programme to prevent severe OHSS.
AB  - BACKGROUND: Withholding gonadotrophins (coasting) can reduce the risk of severe
      ovarian hyperstimulation syndrome (OHSS) in patients having assisted reproduction
      therapy. This requires daily serum estradiol (E(2)) measurements, which
      occasionally have been seen to decline suddenly and sharply. METHODS: To increase
      the sensitivity of the coasting programme we measured serum FSH in parallel with
      E(2) in patients at risk of developing OHSS. RESULTS: Out of a total of 1240
      cycles, 106 were coasted and in 89 both serum E(2) and FSH were measured at least
      twice during the coasting period. One case of late severe OHSS was encountered in
      the study group. The serum FSH declined by a rate of 24.3 +/- 4.5% per day. Serum
      E(2) level reached a 'safe level' of <10,000 pmol/l when the serum FSH declined
      to 5 IU/l or less. CONCLUSION: The results from this study show that measuring
      serum E(2) and FSH can assist in predicting the point at which serum E(2) has
      declined to a level safe enough to administer the trigger HCG.

PMID- 11980742
TI  - A randomized, double blind, placebo-controlled study to investigate the use of
      conscious sedation in conjunction with paracervical block for reducing pain in
      termination of first trimester pregnancy by suction evacuation.
AB  - BACKGROUND: This study evaluated the role of conscious sedation in pain relief
      during termination of first trimester pregnancy by suction evacuation (SE) under
      local anaesthesia. METHODS: A hundred women undergoing SE before 12 weeks
      gestation were randomized by computer using the sealed envelope method to receive
      placebo (saline) or conscious sedation (2 mg midazolam and 25 microg fentanyl)
      i.v. 5 min before cervical dilatation. Paracervical block was given to all
      patients, 2 min later. Pain scores during and after SE, post-operative side
      effects and satisfaction level were compared. RESULTS: No statistically
      significant differences in pain scores were found between the two groups. Post
      operative side-effects such as dizziness (P = 0.015) and drowsiness (P < 0.001)
      were significantly more severe in the conscious sedation group. However, patients
      in the conscious sedation group reported better satisfaction levels than the
      control group (P = 0.003). CONCLUSION: The use of conscious sedation
      significantly improved patient satisfaction during termination of first trimester
      pregnancy by SE under local anaesthesia, despite a lack of improvement in pain
      relief and the presence of increased severe dizziness/drowsiness in the post
      operative period.

PMID- 11980743
TI  - Socio-demographic determinants of intrauterine device use and failure in China.
AB  - BACKGROUND: This study examines social, demographic and family planning programme
      factors influencing intrauterine device (IUD) use, failure and subsequent
      resolution ('use dynamics') in the 1988 Chinese National Survey of Fertility and
      Contraceptive Prevalence. METHOD: A time-to-failure model was used to identify
      independent determinants of IUD failure. Logistic regression was used to identify
      independent predictors of abortion in women after failure. RESULTS: Being younger
      at IUD fitting [<25 versus > or = 35 years, hazard ratio 5.9, 95% confidence
      interval (CI) 4.3, 7.7] and having a larger number of living children (> or = 3
      versus <2 children, hazard ratio 1.2, 95% CI 1.1, 1.4) predict higher risk of IUD
      failure when controlled for each other; but in women with IUD failure, being
      older and having fewer children predict a much higher chance of resulting
      abortion. Contraceptive history and social/regional factors were also associated
      with higher IUD failure risk, in particular, use before 1984 (hazard ratio 1.3,
      95% CI 1.2,1.4); and some of these factors were also predictive of abortion
      following failure. CONCLUSIONS: The determinants of IUD use dynamics suggest two
      main possible mechanisms. Some determinants may reflect effects of the Chinese
      family planning programme; some may indicate women's physiological and biological
      reactions to IUD. Health implications and relevant policy recommendations are
      discussed.

PMID- 11980744
TI  - Anxiolytic premedication reduces preoperative anxiety and pain during oocyte
      retrieval. A randomized double-blinded placebo-controlled trial.
AB  - BACKGROUND: The role of anxiolytic premedication remains unclear and significant
      postoperative side-effects may result from routine use. METHODS: In this double
      blinded study, 100 infertile patients were randomized on the day of ultrasound
      guided oocyte retrieval (TUGOR) by a computer-generated randomization list in
      sealed envelopes to receive either (i) 50 mg pethidine and 25 mg promethazine
      (premedication group) or (ii) normal saline (placebo group) i.m. 30 min prior to
      TUGOR. Anxiety level, pain levels and severity of postoperative side-effects were
      recorded. RESULTS: No differences were seen in demographic data, TUGOR duration,
      number of follicles punctured and clinical outcome. Preoperative anxiety level
      was significantly higher than the basal anxiety level in the placebo group only.
      The vaginal and abdominal pain levels during TUGOR and 4 h after TUGOR were
      significantly higher in the placebo group than the premedication group.
      Significantly more patients complained of drowsiness after TUGOR in the
      premedication group than the placebo group and other side-effects were comparable
      in both groups. CONCLUSION: Routine use of anxiolytic premedication prevented an
      increase of preoperative anxiety level, reduced pain levels during oocyte
      retrieval but was associated with a higher percentage of moderate/severe
      drowsiness in the postoperative period.

PMID- 11980745
TI  - A comparison of four different techniques of assisted hatching.
AB  - BACKGROUND: Assisted hatching (AH) has been proposed as a means to increase the
      implantation rate in patients with poor prognosis for pregnancy. The procedure
      appears to be effective when used selectively. Several different methods for AH
      have been introduced over the years but comparative studies are lacking. The aim
      of the current study was to compare retrospectively the efficacy of AH performed
      with four different methods in patients undergoing IVF or ICSI. METHODS: AH was
      performed prior to day 3 embryo transfer in 794 IVF/ICSI cycles. Indications for
      AH were females aged >35 years and/or elevated follicular phase FSH levels,
      previous failed IVF/ICSI cycles, poor embryo quality, and thick zona pellucida
      (>15 microm). Assignment to one of the four methods of AH was according to the
      availability of the particular method during the study period. The study was not
      randomized. RESULTS: Partial zona dissection was used in 239, acid Tyrode in 191,
      diode laser in 219 and pronase thinning of the zona pellucida in 145. Mean female
      age, mean number of previous failed IVF/ICSI cycles, number of oocytes retrieved,
      fertilization and cleavage rates, good quality embryos and zona thickness on day
      3 did not differ between groups. Mean number of embryos transferred, implantation
      rate, clinical pregnancy rate, and abortion rates were likewise similar.
      CONCLUSIONS: Selective AH using four different methods yields similar
      implantation and pregnancy rates.

PMID- 11980746
TI  - The effect on IVF outcome of small intramural fibroids not compressing the
      uterine cavity as determined by a prospective matched control study.
AB  - BACKGROUND: Several studies have reported that the presence of intramural
      fibroids affects conception following IVF. We attempted to corroborate or refute
      the conclusions relating to IVF and leiomyomas of the aforementioned studies.
      METHODS: Women with small intramural leiomyomata (< or = 5 cm) discovered on
      initial pelvic sonographic studies performed in preparation for IVF were
      prospectively matched by age, with the next patient of the same age undergoing
      IVF who did not demonstrate fibroids (controls). RESULTS: Though no significant
      differences were found in outcome when comparing these two groups, there was a
      distinct trend for lower live delivery rates and higher miscarriage rates.
      CONCLUSIONS: These data support the conclusions of the only other prospective
      matched control study evaluating similar factors, i.e. that small intramural
      fibroids can negatively affect IVF outcome. Nevertheless, we think that a
      multicentre study should be conducted first before evaluating whether myomectomy
      improves outcome or not.

PMID- 11980747
TI  - Combined treatment by pentoxifylline and tocopherol for recipient women with a
      thin endometrium enrolled in an oocyte donation programme.
AB  - BACKGROUND: To evaluate the effect of an antifibrotic treatment by a combination
      of pentoxifylline (PTX) and tocopherol (vitamin E) in patients with a thin
      endometrium who were enrolled in an oocyte donation programme. METHODS: Eighteen
      oocyte recipients who failed to develop a pre-ovulatory endometrial thickness of
      at least 6 mm after receiving vaginal micronized estradiol were enrolled in the
      study. The patients received a combination of PTX (800 mg/day) and vitamin E
      (1000 IU/day) for 6 months. The main outcome measurements were the change in
      endometrial thickness and the pregnancy and delivery rates after treatment.
      RESULTS: Endometrial thickness increased significantly (P <0.001), with a mean of
      (+/-SD) 4.9 +/-0.6 mm before and 6.2 +/- 1.4 mm after treatment, with 72% (13/18)
      of patients being good responders. Five patients either did not respond to the
      treatment or responded only slightly. Three patients, of which two had received
      previous radiotherapy, became spontaneously pregnant, and two became pregnant
      after embryo transfer. Three patients did not have embryo transfer. A total of
      four babies were delivered. The pregnancy rate was thus 33% and the delivery rate
      27%. CONCLUSION: Treatment by combination of PTX and vitamin E appears to improve
      the pregnancy rate in patients with a thin endometrium by increasing the
      endometrial thickness and improving ovarian function. This was especially
      noticeable in patients who had previously received total body irradiation.

PMID- 11980748
TI  - Female sex selection using clomiphene citrate and albumin separation of human
      sperm.
AB  - BACKGROUND: This study was undertaken to assess whether the use of clomiphene
      citrate in conjunction with albumin-separated sperm would alter the sex ratio
      (expressed as the proportion of males) towards females and, if so, whether this
      skewing was due solely to the induction of ovulation. METHODS: The sex ratios of
      184 single and 42 twin births at five assisted reproduction biology clinics were
      determined. The normal approximation to the binomial distribution was used to
      determine significant differences between these sex ratios and the established
      sex ratios for single, twin and combined (single and twin) non- and ovulation
      induced births. RESULTS: The non-ovulation-induced sex ratios for singletons
      (51.4%) and twins (50.2%) were greater than the treatment singleton (27.7%; P <
      0.001) and twin (33.3%; P < 0.01) sex ratios respectively. Correspondingly, the
      non-induced sex ratio for combined births (51.4%) was greater than the treatment
      sex ratio (28.8%; P < 0.001). The previously established induced singleton and
      twin sex ratios (48.1%) were lower than the non-induced sex ratio (51.4%), but
      higher than the treatment singleton (27.7%; P < 0.001) or twin (33.3%; P < 0.03)
      sex ratios. The ovulation-induced combined ratio (48.1%) was less than the non
      induced combined (51.4%) sex ratio, although greater than the treatment combined
      sex ratio (28.8%; P < 0.001). CONCLUSION: Clomiphene citrate in conjunction with
      albumin-separated sperm decreased the sex ratio; a reduction that was not
      exclusively due to induction of ovulation.

PMID- 11980749
TI  - Study of mitochondrial membrane potential, reactive oxygen species, DNA
      fragmentation and cell viability by flow cytometry in human sperm.
AB  - BACKGROUND: Sperm cell death appears to be a cause of male infertility. The
      objective of this study was to determine the most reliable method for the
      evaluation of sperm quality in semen samples during sperm preparation for IVF.
      METHODS: Conventional analysis of semen samples was compared with several
      cytofluorometric methods detecting death-associated changes. Neat semen from
      infertile patients and sperm prepared by PureSperm gradient were studied by
      conventional microscopy and analysed for mitochondrial membrane potential (Delta
      Psi(m)), generation of reactive oxygen species, DNA fragmentation and cell
      viability. RESULTS: In neat semen, a positive correlation was found between the
      percentage of Delta Psi(m)(high) sperm cells and standard semen parameters
      (concentration/motility). Sperm cells depicting Delta Psi(m)(high) and cells with
      low DNA fragmentation displayed high fertilization rate after IVF. The only
      changes that could be detected in prepared sperm were changes in Delta Psi(m),
      with Delta Psi(m)(high) sperm positively correlated with forward motility and
      also with high fertilization rates after IVF. CONCLUSION: Analysis of
      mitochondrial membrane potential is the most sensitive test by which to determine
      sperm quality. These findings promise development of a test that may help to
      predict successful IVF.

PMID- 11980750
TI  - Detection of apoptotic alterations in sperm in subfertile patients and their
      correlations with sperm quality.
AB  - BACKGROUND: The aim of the present study was to define the effect of apoptosis on
      sperm quality and function. METHODS: The apoptotic features in sperm were
      assessed in 60 subfertile subjects, using Annexin-V staining for
      phosphatidylserine (PS) externalization and Tdt-mediated dUTP nick end labelling
      (TUNEL) assay for DNA fragmentation. RESULTS: On average, about 45% of the sperm
      were found to be apoptotic based on the results from Annexin-V staining,
      including both early (Annexin-V-positive, PI-negative) and late apoptosis
      (Annexin-V-positive, PI-positive). TUNEL-positive cells (median value 15%)
      significantly correlated to late apoptosis but not early apoptosis, indicating
      that DNA fragmentation only occurs at the later stage of sperm apoptosis. TUNEL
      positive and late apoptotic cells (Annexin-V-positive, PI-positive) were found to
      be inversely correlated to sperm motility and vitality, and positively to
      abnormal sperm morphology. On the other hand, it is surprising to note that the
      apoptotic alterations in sperm positively correlated to sperm concentration or
      total sperm counts. CONCLUSIONS: Overall results from this study support the
      abortive apoptosis theory; apoptosis in mature sperm is initiated during
      spermatogenesis, after which some cells earmarked for elimination via apoptosis
      may escape the removal mechanism and contribute to poor sperm quality.

PMID- 11980751
TI  - Reliability of the comet assay in cryopreserved human sperm.
AB  - BACKGROUND: Although the comet assay has potential value for measuring DNA damage
      in large epidemiological human sperm studies, it is impractical to perform the
      assay daily on fresh semen samples. Therefore, before its use in epidemiological
      studies, the reliability of the comet assay in measuring DNA damage in
      cryopreserved sperm should be compared with that in fresh human sperm. METHODS:
      Semen samples from 16 men were cryopreserved in liquid nitrogen (LN) using four
      methods: flash freezing with and without cryopreservative, and programmable
      freezing with and without cryopreservative. Neutral microgel electrophoresis was
      performed and comets were stained with YOYO-1. Comet length was measured using an
      eyepiece micrometer at x400 magnification. RESULTS: The highest correlation was
      between comet assay results obtained from fresh human semen compared with semen
      flash frozen without cryopreservative (R = 0.88). However, the method of
      cryopreservation, as compared with other sources of variability, accounted for
      only 6% of the variability. Inter-individual variability accounted for 20%, and
      individual sperm-to-sperm variability within an ejaculate accounted for 65%.
      CONCLUSIONS: Flash-freezing in LN without cryopreservative most closely
      reproduced the results obtained using fresh human semen samples, and thereby
      represents the most appropriate cryopreservation method for human semen in
      epidemiological studies utilizing the neutral comet assay.

PMID- 11980752
TI  - Herpesvirus, cytomegalovirus, human sperm and assisted fertilization.
AB  - BACKGROUND: The effect of viral particles on the motility of human sperm and the
      relationship between sperm and virus are of importance particularly in assisted
      fertilization. METHODS: We incubated ejaculated sperm with or without seminal
      fluid with either herpes simplex virus type 2 (HSV2) or human cytomegalovirus
      (HCMV). For each experiment, 5 x 10(5) sperm were incubated with a viral load of
      between 10(4) and 10(6) plaque-forming units. RESULTS: We detected no apparent
      variations in the percentage of motile forms when sperm were incubated with
      either HSV2 or HCMV. Using a computer-aided semen analysis system, a slight
      difference was reported in the percentage of motile forms when seminal fluid-free
      sperm were incubated with HSV2 (57.18 versus 64.43 in the control). Although the
      mean amplitude of lateral head displacement and the curvilinear velocity were
      significantly higher in infected sperm, the difference in straight line velocity
      was not statistically significantly different. Few viral particles (HSV2 or HCMV)
      adhered to the sperm membrane in the presence of seminal fluid. However, more
      particles stuck when in the absence of seminal fluid, particularly with HSV2 (8%
      of sperm sections for HSV2; 4% for HCMV). CONCLUSIONS: The relationship between
      sperm and viruses depends on the type of virus present as well as the presence or
      absence of seminal fluid. Motility is not a good enough criterion on which to
      prove the presence of viral elements, either in the medium or on the sperm.

PMID- 11980753
TI  - Reduction of steps in the preparation of motile sperm for intrauterine
      insemination does not reduce efficacy of the procedure: simplified one-step swim
      up method versus classic swim-up.
AB  - BACKGROUND: Intrauterine insemination (IUI) is a valid treatment for infertility
      with a cumulative pregnancy rate of >40-90% after 3-10 treatment cycles. We
      studied the efficacy of a simplified method for motile sperm preparation for IUI.
      METHODS: A prospective clinical trial was performed with 100 couples (male age 33
      48 and female 28-37 years) with a 2-8 year history of primary infertility
      associated with slight oligozoospermia (16/100), oligomenorrhoea (32/100) or
      unknown (52/100). Motile sperm for IUI were prepared by: (A) the classic World
      Health Organization self-migration (swim-up) method which includes
      centrifugation, or (B) a simplified one-step swim-up procedure without
      centrifugation. Recombinant FSH was used for ovarian stimulation. Depending on
      the cause of infertility, patients were matched one-to-one at the time of IUI, so
      that when a total of 100 couples had been treated, 50/100 women received sperm
      prepared by method A and 50/100 by method B. RESULTS: A statistically significant
      correlation was found between the percentage motile sperm of the original semen
      sample and the percentage of motile sperm recovered by method A (r = 0.333, P <
      0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P
      < 0.001) was found between the two methods. CONCLUSIONS: The simplified one-step
      swim-up method was as effective as the classic swim-up method, but the former was
      easier and more economical.

PMID- 11980754
TI  - Polyploidy in large-headed sperm: FISH study of three cases.
AB  - BACKGROUND: Macrocephalic or large headed sperm with multiflagella is a rare
      abnormality often associated with infertility. Sperm chromosomal abnormalities
      could be associated with this specific morphological abnormality. METHODS: The
      cytogenetic content of large-headed sperm was assessed by dual and three-colour
      fluorescence in-situ hybridization in three patients carrying this specific
      morphological abnormality. RESULTS: In all patients nearly all sperm contained at
      least one copy of each sex chromosome, and in more than half of them at least two
      copies of either chromosome 1 or 18 were identified. In some sperm a tetraploidy
      was found. CONCLUSIONS: These observations suggested that both meiotic I and II
      divisions were affected by incomplete partition of homologous chromosomes during
      meiosis I and of sister chromatids during meiosis II associated with a failure of
      nuclear cleavage. Furthermore, they provide evidence for a clear relationship
      between a specific morphological abnormality of the sperm and their abnormal
      cytogenetic content. The treatment of infertility using ICSI would probably be
      unsuccessful and have a high genetic risk in these cases.

PMID- 11980755
TI  - ESHRE basic semen analysis courses 1995-1999: immediate beneficial effects of
      standardized training.
AB  - BACKGROUND: Many reports have shown problems with the high variability in results
      of semen analyses. The Special Interest Group in Andrology (SIGA) of the European
      Society of Human Reproduction and Embryology (ESHRE) implemented a standardized
      training course which has been run in different regions of the world on more than
      20 occasions since 1994. The aim of the present analysis was to investigate to
      what extent training resulted in any immediate effects on the variability of
      assessments made by different observers. METHODS: The variability in
      participants' results from the beginning to the end of each course was analysed
      in eight courses given between 1995 and 1999. RESULTS: For assessments of sperm
      concentration, motility, vitality and morphology, substantial improvement was
      seen over the duration of the course. CONCLUSIONS: A comprehensive, structured
      training course does lead to substantial reductions in inter-observer variability
      in semen analysis. This supports our contention that providing a thorough
      theoretical background and repeated practical training, combined with daily
      feedback of results, is highly effective in raising the technical skills of
      laboratory personnel performing semen analysis.

PMID- 11980756
TI  - Embryonic platelet-activating factor: an indicator of embryo viability.
AB  - BACKGROUND: A definitive need exists to identify a biomarker of embryonic
      viability. Platelet-activating factor (PAF) production by human embryos is
      related to pregnancy potential. METHODS: Conditioned embryo culture media were
      obtained following conventional IVF on day 3, with PAF levels and pregnancy
      outcomes correlated. RESULTS: Overall pregnancy rate was 68% (17/25) with a mean
      of 84.1 (+/- 8.5) pmol/l/embryo PAF level. PAF levels ranged from a 216.4
      pmol/l/embryo (pregnant) to a 3.7 pmol/l/embryo (not pregnant). There was a
      significant difference (P < 0.05) in PAF content between pregnant (92.1 +/- 9.5
      pmol/l/embryo) and non-pregnant groups (52.5 +/- 16.6 pmol/l/embryo). Patients
      were categorized into three groups based upon PAF levels: low (< or= 5
      pmol/l/embryo); medium (51-100 pmol/l/embryo) and high (>100 pmol/l/embryo). The
      low (60%) group had a significantly (P < 0.05) lower pregnancy rate than either
      the medium (85%) or high (89%) groups. A receiver-operator characteristic curve
      predicted a cut-off limit of 45 pmol/l/embryo for PAF content in human embryo
      conditioned culture media. CONCLUSIONS: The data demonstrate a correlation
      between PAF levels in human embryo conditioned culture media and pregnancy
      outcome. Additionally, as embryonic PAF levels increase so does the corresponding
      pregnancy rate. Therefore, PAF may be used as an indicator of embryo viability
      and for predicting pregnancy outcome.

PMID- 11980757
TI  - Nuclear competence for maturation and pronuclear formation in mouse oocytes.
AB  - BACKGROUND: In response to gonadotrophins, a fully grown mouse oocyte matures to
      the metaphase of the second meiotic division and becomes competent for the
      development of female and male pronuclei after fertilization. The present study
      was carried out to clarify when during the growth period an oocyte nucleus
      acquires the ability to promote pronuclei formation after fertilization. METHODS:
      Fully grown germinal vesicle (GV) oocytes were enucleated and fused with nuclei
      from growing oocytes from 1-20 day old mice by standard nuclear transfer
      technique. The reconstructed oocytes were matured and fertilized in vitro, and
      pronuclear formation was assessed. RESULTS: The oocytes whose nuclei were
      exchanged for those of the non-growing-stage oocytes matured to the metaphase of
      the second meiotic stage, but no normal female pronuclei were formed. Female
      pronuclei first formed in 27% of the oocytes reconstituted with the nuclei of
      oocytes from 8 day old pups after fertilization. Recondensed sperm chromatin was
      detected in 27% of the oocytes reconstructed with oocyte nuclei from 8 day old
      mice, and a male pronucleus was first formed in 6% of the oocytes that had been
      reconstructed with the nuclei of oocytes from 15 day old mice. The sizes of the
      female and male pronuclei increased with oocyte donor age, and reached normal
      size when the oocytes from 15 and 20 day old mice respectively were used. An
      electron microscopic study using oocytes that had received the oocyte nuclei of 8
      day old mice confirmed these results. CONCLUSION: The factors required for
      pronuclear formation are derived from fully grown GV oocytes, and the
      transformation from decondensed sperm chromatin to a recondensed male pronucleus
      is governed by GV-derived factors.

PMID- 11980758
TI  - Prospective hatching of embryos developed from oocytes exhibiting difficult
      oolemma penetration during ICSI.
AB  - BACKGROUND: The hormonal milieu during ovarian stimulation is known to affect
      oolemma behaviour as well as zona pellucida thickness and structure. This led us
      to investigate whether a special subgroup of patients with oocytes where
      penetration of the oolemma is difficult during ICSI may benefit from assisted
      hatching. METHODS: A total of 77 couples (mean age: 32.9 +/- 4.6 years; range: 22
      38) had oocytes that could hardly be penetrated by the ICSI pipette. Nineteen
      patients underwent two ICSI cycles, giving a total number of 96 cycles, which
      were randomly split into either the study group (n = 52) or the non-hatching
      group (n = 44). Hatching was done using a non-contact 1.48 mm wavelength diode
      laser. Implantation and pregnancy rates were recorded. RESULTS: The pregnancy
      rate was 36.6% (19/52) in the study group and 13.6% (6/44) in the non-hatching
      group (P < 0.05). In addition, a higher number (P < 0.05) of embryos implanted in
      the study group (23/106; 21.7%) than in the non-hatching group (9/92; 9.8%).
      CONCLUSIONS: Once oolema penetration during ICSI has proven difficult,
      prospective hatching of embryos considered for transfer may increase their
      implantation behaviour.

PMID- 11980759
TI  - Parameters guiding selection of best embryos for transfer after cryopreservation:
      a reappraisal.
AB  - BACKGROUND: The purpose of this study was to evaluate the respective influences
      of blastomere survival and resumption of mitosis on the outcome of frozen-thawed
      embryos. METHODS: A retrospective analysis was performed in our centre on 363
      thawing cycles, involving 4-cell day 2 grade 1 embryos with <10% fragmentation.
      RESULTS: A higher implantation rate per transferred embryo was observed when all
      transferred embryos were characterized by fully intact blastomeres (100%
      blastomere survival) as compared with damaged embryos (50 or 75% blastomere
      survival) (22.0 versus 7.2%; P < 0.0001). Moreover, the implantation rate per
      transferred embryo was significantly higher for cleaved embryos compared with
      uncleaved embryos (19.7 versus 3%; P < 0.0001). Transfer of fully intact, cleaved
      embryos resulted in the highest implantation rates compared with transfer of
      damaged and uncleaved embryos (27.4 versus 0%; P < 0.0001). Intermediate
      implantation rates were observed when only one of the two criteria was fulfilled
      (13 versus 11% respectively; P > 0.05). Multivariate analysis showed that the
      clinical pregnancy rate was influenced by both criteria (odds ratio = 3.4 for
      transfer of embryos with six or more cells versus embryos with less than six
      cells. CONCLUSION: The results of our study suggest that the most important
      factor to predict further embryo development is the total number of blastomeres
      in transferred embryos, however they are obtained (good survival and/or
      resumption of mitosis).

PMID- 11980760
TI  - The use of a detailed zygote score after IVF/ICSI to obtain good quality
      blastocysts: the German experience.
AB  - BACKGROUND: Due to improvements in embryo culture, it is now possible to transfer
      embryos 5 days after oocyte retrieval and IVF/ICSI at the blastocyst stage,
      giving a better synchronization with the female reproductive tract. In Germany it
      is illegal to culture more than three embryos. Therefore, there is need for a
      sufficient selection at the pronuclear (PN) stage to select the best zygotes and
      exclude those of poor quality. METHODS: A prospective trial was conducted in 168
      IVF and ICSI cycles including the size, number and alignment of pronuclei and
      nucleoli, cytoplasmic halo effect, the presence of vacuoles and granularity of
      ooplasm. Based on the above criteria, the best zygotes were selected (score <15)
      for embryo transfer on day 5. Blastocysts were classified in eight grades based
      on the cleavage speed. RESULTS: A total of 1450 oocytes were collected, of which
      1119 reached the pronuclear stage. Of the zygotes (n = 424) selected at the PN
      stage, 46% achieved the blastocyst stage after 5 days (grade 1-5), 26% the morula
      stage (grade 6-7) and 28% were arrested (grade 8). The mean zygote score showed a
      significant positive correlation with the mean blastocyst quality in ICSI, but
      not in IVF cycles. A cut-off of 15 was calculated for ICSI cycles giving the best
      discrimination with blastocyst grades (6 versus 7) and number of arrested embryos
      (23 versus 45%) below and above this cut-off. A total of 33 clinical pregnancies
      was achieved (20%). Women conceiving had a significantly better mean blastocyst
      development than those not conceiving. Strong cytoplasmic vacuolization and an
      extreme or no halo effect had a negative effect on blastocyst development.
      CONCLUSIONS: The data show that PN stage morphology is related to blastocyst
      development, but the rate of arrested embryos of almost 30% limits the chance of
      conception under the conditions of the German Embryo Protection Law.

PMID- 11980761
TI  - Laparoscopic surgery is not inherently dangerous for patients presenting with
      benign gynaecologic pathology. Results of a meta-analysis.
AB  - BACKGROUND: Laparoscopic surgery presents a large number of advantages over
      laparotomy. The goal of this work was to check whether these benefits outweigh
      any greater risk of complications. METHODS: The study design was a meta-analysis
      of published data from prospective randomized clinical trials (RCT). For the
      period 1966 to June 2000 we searched Medline and Cochrane Controlled Trial
      Registers and asked the investigators for further details. Meta-analysis was
      carried out with the Cochrane review manager software RevMan 4.1. RESULTS: A
      total of 27 prospective RCT including 3611 women (1809 treated by operative
      laparoscopy and 1802 treated by laparotomy) were enrolled in the meta-analysis.
      The overall risk of complications was significantly lower for patients operated
      by laparoscopic surgery [relative risk (RR) 0.59; 95% confidence interval (CI)
      0.50-0.70]. There was no statistically significant difference concerning the risk
      of major complications with respect to the approach used (RR 1.0; 95% CI 0.60
      1.65). The risk of minor complications was significantly lower for patients
      operated by laparoscopic surgery (RR 0.55; 95% CI 0.45-0.66). Concerning the
      risks of readmission, second procedure and blood transfusion, there was no
      difference between the two groups. Identical results were found when we performed
      a sensitivity analysis including or excluding studies according to the
      methodological score. Subgroup analysis according to how serious the surgery was
      (minor, major, advanced) showed a significant increase in the risk of transfusion
      for advanced procedures performed by laparotomy. CONCLUSIONS: Laparoscopic
      surgery is not inherently dangerous for patients presenting benign gynaecological
      pathologies. The potential risk of complications should no longer be advanced as
      an argument against using laparoscopic surgery rather than laparotomy for an
      operation when the indication allows the choice.

PMID- 11980762
TI  - Complex Mullerian malformation: report of a case with a hypoplastic non-cavitated
      uterus and two rudimentary horns.
AB  - Various classifications have been used for congenital anomalies of the Mullerian
      system. We report a case of a previously unknown anomaly of the uterus, and
      propose its possible embryological causes. The patient presented with primary
      amenorrhoea and infertility, and during laparoscopy three distinct uterine horns
      were observed. The tubes were connected to the two most lateral horns, each
      juxtaposed to a normal ovary. The middle horn had a seemingly normal attachment
      to the right uterosacral ligament, whereas its attachment to the left uterosacral
      ligament appeared attenuated and less normal. Furthermore, the right horn was
      immediately attached to the middle horn, whereas the left horn was, like its
      ipsilateral uterosacral ligament, attached to the middle horn by a more
      attenuated, stretched fibrous bridge. Only the middle horn, with its uterosacral
      ligaments, had an attached, although obstructed, cervix. Ultrasonographic
      examination revealed no endometrium echogeneity in any of these uterine bulbs. No
      etiologic factors were noted in the patient's history; her mother denied known
      ingestion of estrogens or other drugs while carrying her daughter. The
      pathogenesis of this anomaly cannot be clearly defined, but may involve
      sequential embryological errors of duplication of the Mullerian tracts, failure
      of fusion of each set of the Mullerian tracts with expected failed canalization
      of each tract and, finally, agenesis of the medial horn of the left duplicated
      tracts.

PMID- 11980763
TI  - Types of pregnancy loss in recurrent miscarriage: implications for research and
      clinical practice.
AB  - BACKGROUND: In recurrent pregnancy loss, there is much debate about cause and
      association, as exact pathophysiological mechanisms have not been elucidated. The
      aim of this study was to assess whether recurrent pregnancy loss (RPL) patterns
      differ according to causal/associated conditions, suggesting differing disease
      processes. METHODS: Following investigation, 427 women with RPL were classified
      into the following 'diagnostic' groups: idiopathic, oligomenorrhoea,
      antiphospholipid syndrome (APS) and 'possible' APS. A total of 323 subsequently
      conceived, and underwent serial ultrasonography in early pregnancy; of these, 87
      (26.9%) miscarried, and the types of pregnancy loss for the four diagnostic
      groups were allocated to either embryo loss (fetal heart never seen) and fetal
      loss (fetal heart seen prior to pregnancy loss). RESULTS: Overall, there were 75
      embryonic losses and 12 fetal losses. The fetal loss rates in each group were
      similar: idiopathic 5.1%, oligomenorrhoea 3.4%, 'possible' APS 4.9% and APS 4.8%.
      CONCLUSIONS: Serial ultrasound helps to discriminate type of pregnancy loss and
      demonstrates that embryo loss is more common than fetal loss. More importantly,
      pregnancy loss patterns do not seem to differ between diagnostic groups in a
      treated population. The fetal loss rate in each of the diagnostic groups is
      similar to that in other reported populations.

PMID- 11980764
TI  - Ultrastructure of the early human feto-maternal interface co-cultured in vitro.
AB  - BACKGROUND: The study was designed to investigate the ultrastructural features of
      the early human feto-maternal interface when generated by in-vitro co-culture,
      and compare these with findings reported previously from human pregnancies.
      METHODS: Placental villi and decidua parietalis tissues from 8-12 week
      pregnancies were co-cultured in vitro over a 4-day period. The co-incubations
      were ended at 24 h intervals and processed for electron microscopical studies,
      and for immunocytochemistry using anti-cytokeratin antibody (CAM 5.2) for
      trophoblast. RESULTS: Loss of the syncytium at points of contact with the
      decidual stroma, cytotrophoblast column formation, differentiation and invasion
      of extravillous trophoblast (EVT) cells into the decidual stroma over the 4-day
      period of co-culture were observed. Cellular components, such as actin filaments,
      microtubules, glycogen granules and lamellipodic processes found in EVT cells
      were consistent with active cellular locomotion. CONCLUSIONS: These
      ultrastructural studies emphasize the usefulness of this model in investigating
      the formation of the feto-maternal interface of human pregnancy. The recruitment
      of cytotrophoblast to the syncytium by a process involving fusion of the
      intervening plasma membranes, and the migration of EVT cells causing little or no
      damage to the surrounding decidual cells, resemble in-vivo data.

PMID- 11980765
TI  - Comparison between disclosure and non-disclosure approaches for trisomy 21
      screening tests.
AB  - BACKGROUND: First-trimester nuchal translucency (NT) and second-trimester triple
      test (TT) are common screening programmes for trisomy 21. The aim of this study
      was to compare disclosure and non-disclosure approaches of combining those tests.
      METHODS: Likelihood ratios of both NT and TT tests, among 508 normal and 23
      trisomy 21-affected pregnancies, were used for calculating population-adjusted
      risks. Disclosure approach incorporated all cases which, by either NT or TT,
      exhibited a risk > or = 1:250 whereas non-disclosure approach generated a new
      integrated figure > or = 1:250. RESULTS: Among women aged < or = 34 years, the
      disclosure and non-disclosure approaches were associated with false positive
      rates of 4.3 and 1.1%, detection rates of 76.4 and 61.2%, positive predictive
      value (PPV) of 1:53 and 1:17, and false negative rate of 1:3129 and 1:1985
      respectively. CONCLUSIONS: The disclosure approach resulted in considerably
      higher detection rates. The non-disclosure approach, however, was four times
      better regarding the number of invasive procedures required to detect one case of
      trisomy 21. However, the positive predictive value associated with the disclosure
      policy was still much more beneficial than that obtained in women aged > or = 37
      years, who are routinely referred to fetal karyotyping.

PMID- 11980766
TI  - Heterotopic triplet pregnancy: report of a case with bilateral tubal pregnancy
      and an intrauterine pregnancy.
AB  - The first report of an ectopic pregnancy following IVF was published in 1976, and
      since then heterotopic pregnancies (HPs) have been reported at an increasing
      rate. Although cases of the co-existence of a bilateral tubal and an intrauterine
      pregnancy following IVF-embryo transfer have been reported, a case of heterotopic
      triplet pregnancy caused by unilateral tubal embryo transfer has not yet been
      published in the literature. Here we report on a 38-year-old women (gravida 3,
      para 1) with a history of infertility who presented to our infertility clinic for
      evaluation. Hysterosalpingography revealed bilaterally patent Fallopian tubes and
      stricture of the cervical canal. She conceived after receiving HMG combined with
      pure FSH, followed by IVF-tubal embryo transfer. Four embryos were replaced into
      the right tube. Approximately 5 weeks after tubal embryo transfer, the patient
      presented with lower abdominal tenderness and shock due to internal bleeding. She
      underwent an emergency laparotomy under the impression of HP. Bilateral tubal
      pregnancy with right tubal rupture was noted during the operation. The post
      operative course was uneventful. Early intervention and thorough inspection of
      the peritoneal cavity in patients with haemodynamic instability can prevent
      jeopardizing the life of the mother as well as the ongoing pregnancy.

PMID- 11980767
TI  - Testicular changes during infantile 'quiescence' in the marmoset and their
      gonadotrophin dependence: a model for investigating susceptibility of the
      prepubertal human testis to cancer therapy?
AB  - BACKGROUND: Inexplicably, boys treated with some therapies for cancer at age 2-10
      years, a time of supposed 'testicular quiescence', are at risk of low sperm
      counts/infertility in adulthood. Our aims were to use the marmoset as a surrogate
      for man to establish testicular cell function/activity during 'quiescence'
      between the neonatal period and puberty, and to test if any cell activity could
      be suppressed by prior treatment with a GnRH antagonist. METHODS AND RESULTS:
      Based on immunoexpression studies, functional development of Sertoli cells (SGP
      2, androgen receptor) and Leydig cells (3 beta-hydroxysteroid dehydrogenase) was
      detectable at an age (35 weeks) when the testis is considered to be quiescent,
      and in advance of the pubertal rise in blood testosterone levels (50-60 weeks).
      Other changes at 35 weeks were the appearance of focal seminiferous tubule lumens
      and proliferating germ cells [indicated by immunoexpression of proliferating cell
      nuclear antigen (PCNA)]. Treatment from 25 to 35 weeks with GnRH antagonist
      largely (>85%) prevented these changes. However, the PCNA-labelling index of
      spermatogonia in GnRH antagonist-treated animals did not differ from controls
      (41.3 versus 43.6%) though total spermatogonia volume per testis was reduced by
      41%. Some protein markers (inhibin-alpha, estrogen receptor-beta) showed little
      change with age or treatment. Beyond 35 weeks, GnRH antagonist-treated animals
      showed a delay in the pubertal rise in plasma testosterone levels. CONCLUSIONS:
      These findings reinforce the view that the 'childhood' testis is not quiescent.
      This may explain the damaging effects of some cancer therapies on subsequent
      fertility of boys and raises the issue of protective intervention. The present
      studies suggest that GnRH antagonist-based intervention might be only partially
      successful. Identification of the factors regulating spermatogonial development
      in the infant marmoset may aid in the design of such strategies.

PMID- 11980768
TI  - Health profile of middle-aged women: The Women's Health in the Lund Area (WHILA)
      study.
AB  - BACKGROUND: Middle-aged women experience various health-related problems. The aim
      of this study was to evaluate the impacts of menopause status and hormone
      intervention on women's health. METHODS: In an ongoing, population-based study,
      4943 women, born 1935 to 1945 and living in the Lund area of Southern Sweden,
      were included in this analysis. They completed a generic questionnaire pertaining
      to socio-demographic background and current health-related symptoms. Among the
      cohort, 9% of women were pre-menopausal (PM), 52% were post-menopausal without
      hormone replacement therapy (PMO) and 39% were current hormone replacement
      therapy users (PMT). RESULTS: Hot flushes and vaginal dryness were strongly
      related to menopausal status. The prevalence of somatic symptoms worsened
      progressively from the groups of PM to PMO to PMT. The most abundant complaints
      were headache and muscle-skeletal-joint problems. A total of 85% of women
      experienced psychological problems. Contrary to our expectation, a poorer profile
      of psychological health was found in the PMT group when compared with the PMO
      group. CONCLUSIONS: The high prevalence of symptoms in middle-aged women could be
      attributed to age, hormonal influence as well as personality.

PMID- 11980769
TI  - The effect of a change in the dose of trimegestone on the pattern of bleeding in
      estrogen-treated post-menopausal women: 6 month extension of a dose-ranging
      study.
AB  - BACKGROUND: Abnormal bleeding pattern is one major reason for non-compliance with
      hormone replacement therapy (HRT) in post-menopausal women. We have previously
      documented that the dose of trimegestone is the main determinant of the pattern
      of bleeding in women treated with estradiol (E(2)) and sequential combined
      trimegestone administered in four doses. The objectives of this study were to
      test the effect of changing the dose of trimegestone and the duration of
      treatment on the pattern of bleeding in these women who then entered a 6 month
      extension phase where a single dose of trimegestone was given sequentially
      combined with E(2). METHODS: The menstrual diaries of 134 post-menopausal women
      who completed a dose-ranging study of trimegestone and then entered a 6 month
      extension phase were analysed. In the 6 month extension study, all women were
      given one dose of trimegestone (0.25 mg) in a sequential fashion (day 15-28)
      combined with continuous E(2) (2 mg/day). RESULTS: Women who had received
      trimegestone 0.25 mg/day during the first 6 months experienced no change in the
      bleeding pattern in the 6 month extension. Women who had been treated with 0.5
      mg/day dose experienced earlier onset, and more prolonged bleeding (P < 0.0001)
      following the change to 0.25 mg/day. Women who previously received trimegestone
      doses of 0.05 and 0.1 mg experienced a later onset of bleeding, which was lighter
      and of shorter duration (P < 0.001) during the extension phase as compared with
      the first 6 months. CONCLUSION: The dose of trimegestone, and not the duration of
      treatment, appears to be the important determinant of the pattern of bleeding in
      post-menopausal women on this HRT regimen.

PMID- 11980770
TI  - Neonatal outcome and congenital malformations in children born after in-vitro
      fertilization.
AB  - BACKGROUND: To evaluate the neonatal outcome and the prevalence of congenital
      malformations in children born after IVF in northern Finland we carried out a
      population-based study with matched controls. METHODS: Firstly, 304 IVF children
      born in 1990-1995 were compared with 569 controls, representing the general
      population in proportion of multiple births, randomly chosen from the Finnish
      Medical Birth Register (FMBR) and matched for sex, year of birth, area of
      residence, parity, maternal age and social class. Secondly, plurality matched
      controls (n = 103) for IVF twins (n =103) were randomly chosen from the FMBR and
      analysed separately. Additionally, IVF singletons (n = 153) were compared with
      singleton controls (n = 287). Mortality rates were compared with national figures
      from FMBR. RESULTS: Most mortality rates were twice as high as national figures
      in the general population. When compared with the control group representing the
      general population, the incidences of preterm birth [odds ratio (OR) 5.6, 95%
      confidence interval (CI) 3.7-8.6], very low birth weight (OR 6.2, 95% CI 2.0
      19.0), low birth weight (OR 9.8, 95% CI 5.6-17.3), neonatal morbidity (OR 2.4,
      95% CI 1.7-3.4) and hospitalization (OR 3.2, 95% CI 2.2-4.6) were significantly
      higher in the IVF group. The prevalence of heart malformations was four-fold in
      the IVF population than in the controls representing the general population (OR
      4.0, 95% CI 1.4-11.7). CONCLUSIONS: Neonatal outcome after IVF is worse than in
      the general population with similar maternal age, parity and social standing,
      mainly due to the large proportion of multifetal births after IVF. The higher
      prevalence of heart malformations does not solely arise from multiplicity but
      from other causes. In order to improve neonatal outcome after IVF, the number of
      embryos transferred should be limited to a minimum.

PMID- 11980771
TI  - Changes with age in the level and duration of fertility in the menstrual cycle.
AB  - BACKGROUND: Most analyses of age-related changes in fertility cannot separate
      effects due to reduced frequency of sexual intercourse from effects directly
      related to ageing. Information on intercourse collected daily through each
      menstrual cycle provides the data for estimating day-specific probabilities of
      pregnancy for specific days relative to ovulation, and these estimates allow
      unconfounded analysis of ageing effects. METHODS: A total of 782 healthy couples
      using natural family planning methods contributed prospective data on 5860
      menstrual cycles. Day of ovulation was based on basal body temperature
      measurements. Estimates of day-specific probabilities of pregnancy and the length
      of the fertile window were compared across age groups. RESULTS: Nearly all
      pregnancies occurred within a 6 day fertile window. There was no evidence for a
      shorter fertile window in older men or women. On average, the day-specific
      probabilities of pregnancy declined with age for women from the late 20s onward,
      with probabilities of pregnancy twice as high for women aged 19-26 years compared
      with women aged 35-39 years. Controlling for age of the woman, fertility was
      significantly reduced for men aged >35 years. CONCLUSIONS: Women's fertility
      begins to decline in the late 20s with substantial decreases by the late 30s.
      Fertility for men is less affected by age, but shows significant decline by the
      late 30s.

PMID- 11980772
TI  - Subsidised oocyte donation in Israel (1998-2000): results, costs and lessons.
AB  - BACKGROUND: Israeli law stipulates that all women aged 45-51 who need oocyte
      donation are entitled to as many donations as necessary, up to the birth of one
      child. Only oocytes donated by women who themselves are undergoing assisted
      reproduction are allowed. The government subsidizes all oocyte donation cycles
      through the medical insurer of the recipient, whether or not the procedure is
      performed in a public or private institution. The aim of the present study was to
      investigate the success of oocyte donation cycles in Israel for the period 1998
      2000 and to estimate costs and pregnancy rates. METHODS: Data were derived from
      the Dan District Registry of the General Health Services (Sheirutei Bri'ut
      Clalit), the largest medical insurer in Israel. RESULTS: 171 women underwent 254
      oocyte donation cycles within these 3 years, and 45 babies were born, for a
      positive outcome of 17.7%. Average annual cycle cost was US$1742 and average
      annual cost per patient, US$2521. The total annual cost for the district
      accounted for only 0.05% of the budget. CONCLUSIONS: These findings suggest that
      IVF with donated oocytes is relatively efficient and that government funding of
      oocyte donation cycles ensures a reasonable cost.

PMID- 11980773
TI  - III. Gamete and embryo donation.
AB  - Ethical considerations concerning gametes and embryo donation are discussed.
      Basic principles are outlined, focusing on the issues raised by the meaning of
      genetic links, regulation and the necessity for taking into account the welfare
      of the child. Relevant specific aspects concern anonymity, compensation for
      donation and the consent, screening and assessment of donors and recipients.

PMID- 11980774
TI  - IV. Stem cells.
AB  - These pages contain guidelines and other articles compiled by ESHRE Special
      Interest Groups and others, and agreed by the EHSRE Executive Committee. They are
      not submitted to journal peer review. In this fourth statement of the ESHRE
      Taskforce on Ethics and Law, the focus is on ethical issues raised by the
      possible therapeutic use of stem cells, and in particular from embryo stem cells.
      General ethical principles are discussed, including autonomy, beneficience,
      maleficience and freedom of research. Specific points are raised concerning the
      source of embryos for stem cells and of oocytes for somatic cell nuclear
      transfer.

PMID- 11980776
TI  - Prevention of high order multiple pregnancy.

PMID- 11980778
TI  - Successful pregnancy occurred from slowly freezing human oocytes using the regime
      of 1.5 mol/l 1,2-propanediol with 0.3 mol/l sucrose.

PMID- 11980780
TI  - GnRH agonist versus antagonist therapy.

PMID- 11980781
TI  - A life course approach to chronic disease epidemiology: conceptual models,
      empirical challenges and interdisciplinary perspectives.

PMID- 11980782
TI  - Epidemiological challenges in studying the fetal origins of adult chronic
      disease.

PMID- 11980783
TI  - Life course epidemiology and infectious diseases.

PMID- 11980784
TI  - Observations throwing light on the high mortality in the county of Finnmark. Is
      the high mortality today a late effect of very poor living conditions in
      childhood and adolescence? 1973.

PMID- 11980786
TI  - Components in the interpretation of the high mortality in the county of Finnmark.

PMID- 11980787
TI  - Salt, blood pressure and health: a cautionary tale.

PMID- 11980788
TI  - Evidence on salt and blood pressure is consistent and persuasive.

PMID- 11980789
TI  - Salt, blood pressure and public policy.

PMID- 11980790
TI  - Salt, blood pressure and health.

PMID- 11980791
TI  - Salt intake, hypertension and risk of cardiovascular disease: an important public
      health challenge.

PMID- 11980793
TI  - Southampton's Women: by Magda Segal.

PMID- 11980794
TI  - Accumulated labour market disadvantage and limiting long-term illness: data from
      the 1971-1991 Office for National Statistics' Longitudinal Study.
AB  - BACKGROUND: Both social class and unemployment have been shown in many studies to
      be related to ill health. Recent work in social epidemiology has demonstrated the
      importance of examining the accumulation of disadvantage over the life course.
      This paper therefore uses a large longitudinal data set to examine the
      accumulation of both disadvantaged class and unemployment over a 20-year period
      in a representative sample of the male working population of England and Wales.
      METHODS: Logistic regression. RESULTS: Both membership of semi- or unskilled
      social class and unemployment in 1971 were related to limiting long-term illness
      (LLTI) in 1991 independently of each other, and of subsequent social class and
      unemployment. Any occurrence of disadvantaged social class or of unemployment
      added significantly to the risk of LLTI. A labour market disadvantage score
      comprising the number of occasions on which a study member had been either in a
      disadvantaged social class or unemployed showed a clear and graded relationship
      to illness, with odds of 4 to 1 in the worst-scoring group. CONCLUSION: The
      experiences of disadvantaged social class or unemployment at any time during this
      period contributed independently to an increased risk of chronic limiting illness
      up to 20 years later in the life course. Whereas improvements in social
      conditions at any one time will lessen the long-term combined impact of
      accumulated labour market disadvantage on health, it may not prove easy to obtain
      short term improvements in health inequality.

PMID- 11980795
TI  - Birthweight, postnatal growth and cognitive function in a national UK birth
      cohort.
AB  - BACKGROUND: Birthweight is associated with cognition and educational attainment
      across the full birthweight range in the normal population, independently of
      social background. However, the extent to which birthweight reflects fetal
      growth, or is a marker of subsequent size, with respect to this association, is
      not clear. We therefore investigated the independent effects of birthweight and
      postnatal height adjusted for postnatal weight on cognitive function and
      educational attainment while controlling for family background. METHODS: Using
      the British 1946 birth cohort we investigated the association between cognitive
      function at various ages and birthweight, height adjusted for weight in childhood
      and adulthood, and educational attainment, controlling for sex, father's social
      class, maternal education, birth order, and maternal age. RESULTS: Birthweight
      was positively associated with cognition up to age 26, and with the likelihood of
      obtaining advanced educational qualifications. Height was positively associated
      with cognition at all ages, and also with educational attainment. Weight was not
      associated with cognition at ages 8 and 15, but was negatively associated with
      verbal ability at age 26, with verbal memory at age 43, and with educational
      attainment. These effects were independent of each other, and of family
      background. Conditional analyses suggested the positive effect of height growth
      on cognition at two intervals, one in early childhood, and the other in late
      adolescence. In addition, weight gain after age 15 was negatively associated with
      cognition at 26. CONCLUSION: Birthweight and postnatal growth are independently
      associated with cognition.

PMID- 11980796
TI  - Mother's age and daughter's fecundity. An epidemiological analysis of late 19th
      to early 20th century family reconstitutions.
AB  - BACKGROUND: At both ends of the female reproductive span, the risk of
      reproductive problems is increased. We hypothesize that this is partly explained
      by inadequate maturation of oocytes ('pre-ovulatory overripeness'). As this
      phenomenon has been shown to lead to gonadal anomalies in the offspring of
      animals, we tested the prediction that daughters of older and very young mothers
      more often suffer reproductive problems due to ovarian maldevelopment. METHODS:
      We analysed family reconstitutions of 1907 women born in Rotterdam, the
      Netherlands, between 1873 and 1902. We defined several measures of fecundity
      based on numbers, birth rates and fates of offspring. We made use of general
      estimating equations (GEE), a statistical technique that allowed simultaneous
      analysis of different births per woman while controlling for various time
      dependent or time-independent co-variables. RESULTS: The results indicated an
      increased risk of childlessness (adjusted odds ratio (aOR = 2.6, 95% CI : 1.1
      7.4), stillbirth (aOR = 2.5, 95% CI : 1.1-5.6) and multiple birth (aOR = 2.1, 95%
      CI : 0.8-5.4) for daughters of mothers of >or=40 years as compared to daughters
      born to mothers of intermediate age (24-30 years). Daughters of mothers of <or=20
      years, on the other hand, did not appear to have reduced fecundity. CONCLUSION:
      The results point to a decreased fecundity of daughters of older mothers, but not
      of daughters of younger mothers. The inconsistency of the results with respect to
      the oocytal-maturation hypothesis points to the action of other causal or non
      causal mechanisms.

PMID- 11980797
TI  - Socioeconomic status in childhood and the lifetime risk of major depression.
AB  - BACKGROUND: Major depression occurs more frequently among people of lower
      socioeconomic status (SES) and among females. Although the focus of considerable
      investigation, the development of SES and sex differences in depression remains
      to be fully explained. In this study, we test the hypotheses that low childhood
      SES predicts an increased risk of adult depression and contributes to a higher
      risk of depression among females. METHODS: Participants were 1132 adult offspring
      of mothers enrolled in the Providence, Rhode Island site of the US National
      Collaborative Perinatal Project between 1959 and 1966. Childhood SES, indexed by
      parental occupation, was assessed at the time of participants' birth and seventh
      year. A lifetime history and age at onset of major depressive episode were
      ascertained via structured interviews according to diagnostic criteria. Survival
      analyses were used to model the likelihood of first depression onset as a
      function of childhood SES. RESULTS: Participants from lower SES backgrounds had
      nearly a twofold increase in risk for major depression compared to those from the
      highest SES background independent of childhood sociodemographic factors, family
      history of mental illness, and adult SES. Analyses of sex differences in the
      effect of childhood SES on adult depression provided modest support for the
      hypothesis that childhood SES contributes to adult sex differences in depression.
      CONCLUSIONS: Low SES in childhood is related to a higher risk of major depression
      in adults. Social inequalities in depression likely originate early in life.
      Further research is needed to identify the pathways linking childhood conditions
      to SES differences in the incidence of major depression.

PMID- 11980798
TI  - Infant mortality at time of birth and cause-specific adult mortality among
      residents of the Region of Madrid born elsewhere in Spain.
AB  - BACKGROUND: To investigate the association between infant mortality at time of
      birth and mortality from various causes of death in adulthood in men and women.
      METHODS: Linked mortality study based on mortality records for 1996 and 1997 and
      on 1996 population census data of the Region of Madrid (Spain). Deaths from five
      cancer sites and from five chronic diseases were estimated for 1 224 894 people
      aged 35-74 years residing in the Region of Madrid who were born elsewhere in
      Spain. RESULTS: A gradient in mortality by infant mortality quartile was seen for
      mortality from stomach cancer, colon cancer, diabetes mellitus and chronic liver
      disease in men, and for stomach cancer, ischaemic heart disease and chronic liver
      disease in women. The association was positive for stomach cancer and negative
      for all other causes. The relative mortality rates adjusted for age and adult
      socioeconomic factors for men belonging to infant mortality quartiles 3 and 4
      (highest) versus those belonging to quartiles 1 and 2 as baseline were 1.06 (95%
      CI : 0.75-1.56) for stomach cancer, 0.67 (95% CI : 0.47-0.95) for colon cancer,
      0.59 (95% CI : 0.35- 1.00) for diabetes mellitus, and 0.70 (95% CI : 0.49-0.99)
      for chronic heart disease. The relative mortality rates for women were 2.06 (95%
      CI : 1.09-3.88) for stomach cancer, 0.58 (95% CI : 0.41-0.80) for ischaemic heart
      disease, and 0.44 (95% CI : 0.27-0.70) for chronic liver disease. CONCLUSION:
      Higher infant mortality at time of birth is associated with adult mortality from
      diabetes mellitus and colon cancer in men, from ischaemic heart disease in women,
      and from stomach cancer and chronic liver disease in both sexes. These results
      most likely reflect adverse living conditions and/or nutritional deprivation in
      childhood.

PMID- 11980799
TI  - A population-based case-control study for examining early life influences on
      geographical variation in adult mortality in England and Wales using stomach
      cancer and stroke as examples.
AB  - BACKGROUND: Geographical variation in mortality is influenced by factors
      operating in early life and in adulthood. The relative contributions of these
      factors may be examined by comparing the extent to which adult mortality is
      related to places of residence in early life and at death. We describe a
      population-based case-control design, in which all deaths are used as cases and
      the Office for National Statistics (ONS) Longitudinal Study (LS) survivors are
      used as controls. METHODS: Cases were all deaths from stomach cancer and stroke
      in England and Wales 1993-1995 amongst people born between January 1930 and
      September 1939 and for whom place of enumeration in 1939 could be imputed from
      the first three characters of their National Health Service number. Controls were
      all LS members born in the same period, enumerated in the 1991 census, resident
      in England and Wales in mid-1994 and for whom place of enumeration in 1939 could
      be similarly imputed. Logistic regression was used, adjusting for birth year, sex
      and social class. A previous mapping exercise by ONS generated comparable
      geographical units (counties) for 1939 enumeration and area of residence in 1991
      or at death. 'Non-migrant' (i.e. 1939 'county' the same as county in 1991 or at
      death) case:control ratios were calculated to indicate background mortality risk
      in counties, with adjustment for imprecision using Bayesian smoothing methods.
      These ratios were then used in modelling risk for inter-county migrants. RESULTS:
      There were 2590 stomach cancer and 7778 stroke deaths and 28,400 men and 28,180
      women as controls. For men, 64%, 61% and 67% of stomach cancer deaths, stroke
      deaths and controls respectively could be assigned a county of enumeration in
      1939. The corresponding percentages for women were 76%, 72% and 75%. For stomach
      cancer, after adjustment for county of enumeration in 1939, a significant
      association with the non-migrant case:control ratio for county of residence in
      1991 or at death was observed (P= 0.010), indicating an association between
      current area of residence and stomach cancer mortality. There was no evidence of
      an independent effect of county of enumeration in 1939. For stroke, there was a
      highly significant trend in relation to 1939 county (P = 0.0004)and a less
      significant association with county of residence in 1991 or at death(P = 0.016).
      CONCLUSIONS: The method described is able to detect the effect of place of
      residence in early life on geographical variation in adult mortality and will be
      useful for investigating specific characteristics of areas of enumeration in 1939
      in relation to subsequent risk of mortality from a range of diseases.

PMID- 11980800
TI  - Leg and trunk length at 43 years in relation to childhood health, diet and family
      circumstances; evidence from the 1946 national birth cohort.
AB  - BACKGROUND: This is a study of the associations of adult leg and trunk length
      with early life height and weight, diet, socioeconomic circumstances, and health,
      and parental height, divorce and death. METHOD: The data used were collected in a
      longitudinal study of the health, development and ageing of a British national
      birth cohort (N = 2879 in this analysis) studied since birth in 1946. Multiple
      regression models were used to investigate the relationships. RESULTS: Adult leg
      and trunk length were each positively associated with parental height,
      birthweight, and weight at 4 years. Leg length was associated positively with
      breastfeeding and energy intake at 4 years. Trunk length was associated
      negatively with serious illness in childhood and possibly also parental divorce,
      but not with the dietary data. CONCLUSION: Adult leg length is particularly
      sensitive to environmental factors and diet in early childhood because that is
      the period of most rapid leg growth. Trunk growth is faster than leg growth after
      infancy and before puberty, and may be associated with the effects of serious
      illness and parental separation because of the child's growing sensitivity to
      stressful circumstances, as well as the result of the biological effects of
      illness.

PMID- 11980801
TI  - Can adult anthropometry be used as a 'biomarker' for prenatal and childhood
      exposures?

PMID- 11980802
TI  - Life course socioeconomic conditions and adult psychosocial functioning.
AB  - BACKGROUND: Various psychosocial factors have been linked to adult physical
      health and are also associated with socioeconomic position in adulthood. We
      evaluated the effect of socioeconomic conditions over the life course on measures
      of psychosocial functioning in adulthood. METHODS: Life course socioeconomic
      position was assessed by retrospective recall of parents' education and
      occupation when the respondent was age 10, and the respondents' education,
      occupation, and income in 2585 men from eastern Finland aged 42, 48, 54, and 60
      years. Measures of psychosocial functioning were derived from scales measuring
      cynical hostility, hopelessness, and depressive symptoms. RESULTS: Men with both
      parents who had less than a primary school education or who both had unskilled
      manual jobs had higher age-adjusted levels of cynical hostility, hopelessness,
      and depressive symptoms in adulthood. Mutually adjusted analyses showed that
      parents' education and the respondents' education, occupation, and income all had
      statistically independent effects on adult levels of cynical hostility and
      hopelessness. For instance, men for whom neither parent had completed primary
      education had a 0.15 standard deviation (P = 0.006) higher cynical hostility
      score, and a 0.20 standard deviation (P = 0.00018) higher hopelessness score,
      after adjustment for education, occupation and income. In contrast, depressive
      symptoms in adulthood were only associated with the respondent's occupation and
      income. CONCLUSIONS: Childhood socioeconomic position was associated with adult
      psychosocial functioning, but these effects were specific to some aspects of
      adult psychosocial functioning--cynical hostility and hopelessness, but not
      depressive symptoms. Adult occupation and income were associated with all
      measures of psychosocial functioning. In addition to the impact of adult
      socioeconomic position, some aspects of poor psychosocial functioning in
      adulthood may also have socioeconomic roots early in life.

PMID- 11980803
TI  - Childhood socioeconomic status, life course pathways and adult mental health.

PMID- 11980804
TI  - Prenatal factors, childhood growth trajectories and age at menarche.
AB  - BACKGROUND: In recent studies a larger birth size has been shown to delay the
      timing of menarche. The mechanisms underlying this association are not clear,
      however, as birthweight is a predictor of body size in childhood, and a large
      body size is known to be associated with an early onset of menarche. METHODS:
      Data from a representative British cohort of 2547 girls born in 1946 who were
      followed prospectively throughout childhood were used. Information was available
      on prenatal characteristics, birthweight, height, weight and social circumstances
      during childhood, and on age at menarche. Random coefficients models were used to
      estimate the individual trajectories in height and body mass index (BMI) up to
      age 7 years. The parameters identified by these models were then included in
      Weibull survival models for the timing of menarche together with birthweight.
      RESULTS: Birthweight was found to positively influence height and BMI values at
      age 2 years, but not to affect their rates of change from age 2 to 7 years.
      Initial analyses showed low birthweight to be associated with an early onset of
      menarche, but after controlling for growth in infancy this effect was reversed,
      with girls who were heavy at birth reaching menarche earlier than others with
      similar infant growth. Rapid growth in infancy was also related to early pubertal
      maturation. The effects of birthweight and infant growth disappeared, however,
      when further controlled for growth from age 2 to 7 years. CONCLUSIONS: The
      effects of birthweight and growth in infancy on the timing of menarche seem to be
      mediated through growth in early childhood. These findings are consistent with
      the possibility that timing of menarche may be set in utero or early in life,
      although it may be modified by changes in body size and composition in childhood.

PMID- 11980805
TI  - Fetal environment and subsequent obesity: a study of maternal smoking.
AB  - BACKGROUND: The intrauterine environment may influence the development of
      obesity, but as yet, the long-term effect of growth in utero is unclear. We
      studied maternal smoking during pregnancy to gain insight on how an insult
      affecting fetal growth might subsequently influence obesity risk through
      childhood to age 33. METHODS: Data from the 1958 British birth cohort (all births
      in England, Wales and Scotland, 3-9 March 1958), including body mass index (BMI),
      maternal smoking during pregnancy and several potential confounding factors. We
      assessed obesity risk at ages 7, 11, 16, 23 and 33 associated with maternal
      smoking. Adjusted odds ratios (OR) for obesity at age 33 were estimated for 2918
      men and 2921 women with complete data. RESULTS: Infants of mothers who smoked in
      pregnancy were lighter at birth than infants of non-smokers, but from adolescence
      (age 11 for females, 16 for males) they had an increased risk of being in the
      fattest decile of BMI. The OR for obesity associated with maternal smoking
      increased with age, suggesting strengthening of the relationship over time. At
      age 33 the OR was 1.56 (95% CI : 1.22-2.00) for men and 1.41 (95% CI : 1.12-1.79)
      for women. This was robust to adjustment for factors in early life, childhood and
      adulthood. CONCLUSIONS: An elevated risk of obesity among the offspring of
      smokers was not accounted for by other known influences. Findings are consistent
      with a long-term effect of intrauterine environment on adiposity, possibly
      through fetal nutrition, although other mechanisms should be investigated in
      future studies of obesity.

PMID- 11980806
TI  - Maternal smoking during pregnancy and obesity in the offspring.

PMID- 11980807
TI  - Estimating causal effects.

PMID- 11980808
TI  - Counterfactuals: help or hindrance?

PMID- 11980809
TI  - Estimating causal effects.

PMID- 11980810
TI  - Population versus individual level causal effects.

PMID- 11980811
TI  - Estimating causal effects.

PMID- 11980813
TI  - Reproducibility of skin characteristic measurements and reported sun exposure
      history.
AB  - BACKGROUND: The aim of the present study is to investigate the reproducibility of
      information on sun exposure, skin characteristics and sunburn collected through a
      standardized questionnaire used in the multi-centre South European case-control
      study on skin cancer, 'Helios'. We also intended to use results from
      reproducibility analysis for correcting odds ratio (OR) estimates from the
      original study. METHODS: We re-interviewed, with the same questionnaire, a sample
      of 115 cases of basal cell and squamous cell carcinoma of the skin and 119
      population controls, 18-26 months apart, in four centres of Italy, Spain and
      France. The questionnaire included questions on skin characteristics, sunburns
      and sun exposure histories. We investigated agreement, studying the association
      between the difference of the two measures and a set of explanatory variables.
      According to the results of the reproducibility analysis we corrected OR
      estimates from the original study simultaneously adjusting for random measurement
      error. RESULTS: Hair and eye colour showed high agreement with intra-class
      correlation coefficients (ICC) of 0.81 and 0.74, respectively. Lifetime sun
      exposure showed substantial agreement with ICC ranging from 0.68 for time spent
      doing outdoor work to 0.79 for time spent outdoors during holidays and holidays
      at the beach. The poorest agreement was found for number of lifetime sunburns
      (ICC = 0.25), while sunburns during childhood showed a substantial agreement
      (Cohen's Kappa = 0.67). Lack of reproducibility was mainly associated with
      subjects' education, while no significant differences were observed between cases
      and controls. The corrected OR showed a moderate increase with a reinforcement of
      the effect of sun exposure and skin reaction to sun exposure. CONCLUSION:
      Overall, there was good reproducibility, particularly in the case of sun exposure
      histories, between answers given on two different occasions to a questionnaire
      administered by trained interviewers. However, since measurement error can
      substantially bias OR toward the null value, it should be taken into account in
      estimates of the effect of sun exposure on risk of skin cancer.

PMID- 11980814
TI  - Reproducibility of skin characteristic measurements and reported sun exposure
      history.

PMID- 11980815
TI  - How well do antenatal clinic (ANC) attendees represent the general population? A
      comparison of HIV prevalence from ANC sentinel surveillance sites with a
      population-based survey of women aged 15-49 in Cambodia.
AB  - BACKGROUND: The purpose of this study was to evaluate whether HIV-1 prevalence
      among antenatal clinic (ANC) attendees in Cambodia provided a reasonable estimate
      of HIV-1 prevalence among all women 15-49 years. METHODS Antenatal clinic
      attendees in five HIV sentinel surveillance sites (five provinces) were selected
      by consecutive sampling (n = 1695). The population survey of females by household
      was carried out in the same five areas. Household females aged 15-49 years were
      selected using a three-stage cluster sampling design (n = 3066). Serum-based HIV
      ELISA testing was done for both ANC attendees and household females. The HIV
      prevalence for ANC attendees and household females were compared by age group and
      urban versus rural location. RESULTS: The overall prevalence of HIV-1 infection
      among ANC attendees (1.62%, 95% CI : 1.26-1.98) was similar to the overall
      prevalence obtained from the general population of household females (1.24%, 95%
      CI : 0.92-1.55) in the same catchment areas in Cambodia. In the rural areas, the
      overall HIV prevalence among ANC attendees (2.18%, 95% CI : 1.59-2.77) was
      significantly higher than among the household females (0.86%, 95% CI : 0.49-1.23)
      after adjustment for age distribution and education level. In the 15-24 age group
      in rural areas, the HIV prevalence of ANC women was 2.71% (95% CI : 0.96-4.46)
      compared with 0.77% (95% CI : 0.02-1.53) in household females. CONCLUSIONS:
      Although ANC data can be used to estimate trends over time, it should be realized
      that ANC data may overestimate the actual prevalence in the younger age group in
      rural areas in Cambodia.

PMID- 11980816
TI  - Use of period analysis for providing more up-to-date estimates of long-term
      survival rates: empirical evaluation among 370,000 cancer patients in Finland.
AB  - BACKGROUND: Providing up-to-date estimates of cancer patient survival rates is an
      important task of cancer registries. A few years ago, a new method of survival
      analysis, denoted period analysis, was proposed to enhance the recency of long
      term survival estimates. The aim of this paper is to provide a comprehensive
      empirical evaluation of the use of this method. METHODS: Using data from the
      nationwide Finnish Cancer Registry, we compare 5-year and 10-year relative
      survival rates of 371 849 patients diagnosed with one of the 16 most common forms
      of cancer in Finland at various time intervals between 1953 and 1992 with the
      most up-to-date estimates of 5-year or 10-year relative survival that might have
      been obtained in those time intervals by traditional methods of survival analysis
      and by period analysis of survival. RESULTS: Survival rates strongly increased
      over time for most forms of cancer. For these cancers, traditional estimates of 5
      and 10-year survival rates would have severely lagged behind the survival rates
      later observed for newly diagnosed patients, and period analysis would
      consistently have provided much more up-to-date estimates of survival rates.
      CONCLUSIONS: We conclude that period analysis should be implemented as a standard
      tool for providing up-to-date estimates of long-term survival rates by cancer
      registries.

PMID- 11980817
TI  - A nomogram for single-stage cluster-sample surveys in a community for estimation
      of a prevalence rate.
AB  - BACKGROUND: Proper assessment of the magnitude of the problem is essential for
      devising adequate allocation of available resources and for developing future
      strategies to combat a disease. The cluster random sampling (CRS) technique is
      commonly used for rapid assessment of public health problems in developing
      countries. Our objective is to devise a nomogram that can instantly provide the
      number of clusters of specified size needed to estimate the prevalence rate of a
      disease in a community with given precision, ratio of design-effect to cluster
      size and confidence level. This would be applicable only to single-stage CRS.
      METHODS: We use a logarithmic transformation to linearize the relation between
      the number of clusters (C) on one side and design-effect (D), cluster size (B),
      precision (L), anticipated prevalence rate (P) and confidence level (alpha) on
      the other. By using this relation, we construct a nomogram using established
      methods. RESULTS: A nomogram is obtained that can be used to determine the number
      of clusters needed in a survey with the help of only a ruler when other
      parameters are known. This is a 6-in-1 figure as it gives the number of clusters
      C corresponding to any combination of alpha from among the popularly used 0.05,
      0.10 and 0.20, and precision 10% of P or 20% of P. Using a very simple
      calculation, the number of clusters for the other values of alpha and L can also
      be obtained. CONCLUSION: This nomogram can be a useful aid in instantly providing
      the number of clusters required to rapidly estimate the prevalence rate of a
      disease in a community when the ratio of design-effect to cluster size,
      confidence level, and precision are specified. However, it is not applicable to
      intervention studies where interest mainly focuses on testing a hypothesis rather
      than estimation.

PMID- 11980818
TI  - Gastric cancer mortality in the spouses of patients who died from gastric cancer.
AB  - BACKGROUND: There is evidence to support the hypothesis that the main
      determinants of gastric carcinogenesis act in childhood and adolescence. Based on
      the assumption that husband and wife share many of these factors (dietary habits
      and other exogenous exposures) only in adult life, the aim of the study was to
      demonstrate that the spouses of patients who died from gastric cancer (GC) are
      not at increased risk of GC death. METHODS: The study was conducted on data from
      the province of Forli (north eastern Italy). The anonymous GC death records
      provided by the Italian National Statistics Bureau for the years 1969-1988 were
      matched by month/year of birth, sex, marital status, month/year and place of
      death with those of the population registries in the area. The subjects
      identified had a total of 2720 wives or husbands. Gastric cancer mortality
      observed in the cohort of spouses was compared with that of the general
      population using the standardized mortality ratio (SMR), calculated by applying
      the sex-, age-, and time period-specific mortality rate in the population to the
      appropriate person-years at risk in the cohort. RESULTS: The cohort yielded a
      total of 22 414 person-years. The SMR was 1.1 (95% CI : 0.9-1.5) with a value of
      0.9 (95% CI : 0.6-1.5) among males and 1.2 (95% CI : 0.9-1.7) among females.
      CONCLUSION: The study provided further evidence that the main events in gastric
      carcinogenesis occur before adult life.

PMID- 11980819
TI  - Preventable causes of gastric cancer may also operate in adult life.

PMID- 11980820
TI  - Risk of first non-fatal myocardial infarction negatively associated with olive
      oil consumption: a case-control study in Spain.
AB  - BACKGROUND: Olive oil is the main source of dietary lipids in most Mediterranean
      countries where mortality and incidence rates for coronary heart disease (CHD)
      are the lowest in Europe. Although international comparisons and mechanistic
      reasons support the hypothesis that a high olive oil intake may prevent CHD,
      limited data from studies of individuals are available. METHODS: A hospital-based
      case-control study was conducted in Pamplona (Spain) recruiting 171 patients (81%
      males, age <80 years) who suffered their first acute myocardial infarction and
      171 age-, gender- and hospital-matched controls (admitted to minor surgery,
      trauma or urology wards). A validated semi-quantitative food frequency
      questionnaire (136 items) was used to appraise previous long-term dietary
      exposures. The same physician conducted the face-to-face interview for each case
      patient and his/her matched control. Conditional logistic regression modelling
      was used to take into account potential dietary and non-dietary confounders.
      RESULTS: The exposure to the upper quintile of energy-adjusted olive oil (median
      intake: 54 g/day) was associated with a statistically significant 82% relative
      reduction in the risk of a first myocardial infarction (OR = 0.18; 95% CI : 0.06
      0.63) after adjustment for dietary and non-dietary confounders. CONCLUSIONS: Our
      data suggest that olive oil may reduce the risk of coronary disease. These
      findings require confirmation in further observational studies and trials.

PMID- 11980821
TI  - Is olive oil a key ingredient in the Mediterranean recipe for health?

PMID- 11980822
TI  - Self-reported asthma symptoms in children and adults of Bangladesh: findings of
      the National Asthma Prevalence Study.
AB  - BACKGROUND: No population-based studies to determine the magnitude of the asthma
      problem have been carried out in Bangladesh. This study aimed to define the
      prevalence of asthma as well as to identify the risk factors of asthma in the
      general population of Bangladesh. METHODS: A cross-sectional study was conducted
      from January 1999 to August 1999 on 5642 Bangladeshi people. Data were collected
      from randomly selected primary sampling units of 8 municipality blocks of 4 large
      metropolitan cities, 12 municipality blocks of 6 district towns and 12 villages
      of 6 districts chosen randomly from all 64 districts of the country. Face-to-face
      interviews were performed with the housewives or other guardians at the household
      level using a structured questionnaire. RESULTS: The prevalence of asthma (wheeze
      in the last 12 months) was 6.9% (95% CI : 6.2-7.6). The prevalence of other
      asthma definitions were: ever wheeze (lifetime wheeze) 8.0% (95% CI : 7.3-8.7);
      perceived asthma (perception of having asthma) 7.6% (95% CI : 6.9-8.3); doctor
      diagnosed asthma (diagnosis of asthma by any category of doctor either qualified
      or unqualified) 4.4% (95% CI : 3.9-4.9). The prevalence of asthma in children (5
      14 years) was higher than in adults (15-44 years) (7.3% versus 5.3%; odds ratio
      [OR] = 1.41, 95% CI : 1.09-1.82). Asthma in children was found to be
      significantly higher in households with <or=3 people than in larger households
      (OR = 2.20, 95% CI : 1.24-3.20). The low-income group (OR = 1.41, 95% CI : 1.04
      1.92) and illiterate group (OR = 1.51, 95% CI : 1.01-2.24) were more vulnerable
      to asthma attacks than the high-income group and more educated people,
      respectively. CONCLUSIONS: Asthma in Bangladesh appears to be a substantial
      public health problem: an estimated 7 million people including 4 million children
      suffer from asthma-related symptoms.

PMID- 11980823
TI  - Does the 'hygiene hypothesis' provide an explanation for the relatively low
      prevalence of asthma in Bangladesh?

PMID- 11980824
TI  - Analysis of the geographical distribution of sporadic Creutzfeldt-Jakob disease
      in France between 1992 and 1998.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare fatal dementia caused by a
      transmissible agent. However, the mechanism leading to the disease is unknown in
      the majority of cases. The presence of geographically clustered cases might
      indicate a common environmental exposure to the transmissible agent, or case-to
      case transmission of the agent. This study sought evidence of clustering of cases
      of sporadic CJD in France. METHODS: A total of 402 individuals who died from
      definite or probable sporadic CJD in France between 1992 and 1998 were analysed.
      The geographical distribution of cases was analysed using three different
      clustering methods. An analysis of the distribution of the distances between
      pairs was performed to look for evidence of clustering. Then, two methods of
      cluster detection were used to identify the locations of clusters. RESULTS: Each
      of our analyses found some evidence of clustering, though the extent of that
      clustering differed between approaches. The strongest evidence, statistically,
      related to three cases living in a small rural area in South-West France (P =
      0.001). Two of the three cases lived in the same area throughout life. They had
      also both undergone surgery on several occasions. Little information is available
      on the third case. CONCLUSION: Some sporadic CJD cases in France may be
      aetiologically linked. There was strong evidence that three cases in South-West
      France formed a cluster but the precise mechanism underlying this cluster of
      cases remains unclear. The potentially long incubation period of the disease
      makes the identification of links between such cases difficult.

PMID- 11980825
TI  - Geographical distribution of sporadic Creutzfeldt-Jakob Disease in France.

PMID- 11980827
TI  - Heterocopulative syndrome: clinico-pathologic correlation in 260 cases. 1998.

PMID- 11980830
TI  - Structural adjustment in health in Pakistan: defining the questions.

PMID- 11980831
TI  - Birthplace and survival among Asian women diagnosed with breast cancer in cancer
      registry data: the impact of selection bias.

PMID- 11980832
TI  - Authors' response to commentaries on Outcomes in Occupational Cancer
      Epidemiology.

PMID- 11980835
TI  - Introduction of Russell G. Foster, the 2001 recipient of the david g. Cogan
      award.

PMID- 11980836
TI  - Keeping an eye on the time: the Cogan Lecture.

PMID- 11980837
TI  - Introducing David S. Papermaster, the 2001 recipient of the friedenwald award.

PMID- 11980838
TI  - The birth and death of photoreceptors: the Friedenwald Lecture.

PMID- 11980839
TI  - Introducing David Regan, the 2001 recipient of the proctor medal.

PMID- 11980840
TI  - A hypothesis-based approach to clinical psychophysics and to the design of visual
      tests: the Proctor Lecture.

PMID- 11980841
TI  - Introducing Herbert E. Kaufman, the 2001 recipient of the weisenfeld award.

PMID- 11980842
TI  - Can we prevent recurrences of herpes infections without antiviral drugs? The
      Weisenfeld Lecture.

PMID- 11980843
TI  - Expression of a wide range of extracellular matrix molecules in the tendon and
      trochlea of the human superior oblique muscle.
AB  - PURPOSE: To show that the molecular composition of the extracellular matrix of
      the trochlea and its associated tendon may explain the link between some cases of
      acquired Brown syndrome and rheumatoid arthritis. METHODS: One trochlea and its
      tendon from 11 dissecting-room cadavers were fixed in methanol, cryosectioned,
      and immunolabeled with a panel of monoclonal antibodies against types I, II, III,
      V, and VI collagens, chondroitin-4 and -6, keratan and dermatan sulfates,
      aggrecan, link protein, versican, and tenascin. Labeling was detected with an
      avidin-biotin-peroxidase detection kit. RESULTS: The trochlea had a central core
      of hyaline cartilage surrounded by a band of fibrocartilage, but the tendon had
      no cartilage cells. Significantly, however, both structures immunolabeled for
      aggrecan, link protein, and type II collagen-molecules typical of articular
      cartilage. CONCLUSIONS: The presence of aggrecan, link protein, and type II
      collagen may account for the coincidence between transient attacks of acquired
      Brown syndrome in patients with juvenile and adult forms of chronic rheumatoid
      arthritis. Cleavage of aggrecan by aggrecanase in articular cartilage
      characterizes cartilage degeneration in rheumatoid arthritis. Thus, it is
      possible that aggrecan cleavage also occurs in the trochlea and tendon and
      contributes to their degeneration or to a local inflammatory reaction that may
      swell and thicken the tendon. In this context, it is also significant that link
      protein and type II collagen are now regarded as relevant antigenic targets for
      autoimmune responses in rheumatoid arthritis.

PMID- 11980844
TI  - Analyses of the guanylate cyclase activating protein-1 gene promoter in the
      developing retina.
AB  - PURPOSE: To determine the activity, cell specificity, and developmental
      expression profiles of fragments of the chicken guanylate cyclase activating
      protein (GCAP)-1 promoter. METHODS: The intrinsic activities of five GCAP1
      promoter-luciferase constructs were measured in transiently transfected primary
      chicken embryonic retinal cultures. Lentivirus vectors carrying GCAP1 promoter
      nlacZ transgenes were used to examine the cell specificities and temporal
      expression characteristics of selected promoter fragments in developing retina.
      RESULTS: Three of the five GCAP1 promoter fragments exhibited significant
      activity in vitro. The expression characteristics of the promoter fragments in
      vivo varied as a function of promoter length. Expression of nlacZ driven by the
      0.6- and 1.7-kb GCAP1 promoter fragments was first observed on embryonic day
      (E)12 and was restricted to the inner nuclear layer (INL). By E16, nlacZ staining
      was also detected in the outer nuclear layer (ONL). Expression of nlacZ driven by
      the 4.2-kb GCAP1 promoter fragment was not observed until E16 and was restricted
      to the ONL. CONCLUSIONS: The general organization of regulatory cis elements
      within the GCAP1 promoter is different from other photoreceptor-specific gene
      promoters. Elements located within 0.3 kb upstream of the transcription start
      point are capable of producing efficient gene expression; however, additional
      elements located within 4.0 kb upstream of the transcription start point are
      necessary to confer on the fragment the cell specificity and developmental
      expression characteristics of the native GCAP1 promoter. The results of the
      current study show that the lentiviral vector system is a useful tool for the
      characterization of the promoters of genes expressed in neural retina.

PMID- 11980845
TI  - Impaired expression and promotor hypermethylation of O6-methylguanine-DNA
      methyltransferase in retinoblastoma tissues.
AB  - PURPOSE: To investigate the role of epigenetic changes in the promoter region of
      tumor-suppressor genes in the retinoblastoma genome and to study the disruption
      of expression of O6-methylguanine-DNA Methyltransferase (MGMT) due to aberrant
      methylation and its association with retinoblastoma. METHODS: A series of 23
      retinoblastoma tissue specimens and 2 retinoblastoma cell lines (Y79 and WERI
      Rb1) were subjected to methylation-specific PCR (MSP) analysis of hypermethylated
      genes identified in human cancers, including p14(ARF), p15(INK4b), p16(INK4a),
      VHL, and MGMT. Further, the expression of MGMT was studied by
      immunohistochemistry and, when fresh tissue was available, by Western blot
      analysis and RT-PCR. RESULTS: Aberrant methylation of at least one MGMT locus was
      detected in 8 of the 23 tumors (35%), all of which (100%) had impaired or absent
      expression of MGMT. The remaining 15 tumor specimens were nonmethylated, and,
      among them, 7 (43%) showed defective expression. No methylation of tumor DNA was
      found on the p14(ARF), p15(INK4b), p16(INK4a), and VHL genes. Hypermethylation in
      the MGMT promoter was found to be prominently present in retinoblastoma with poor
      tissue differentiation, and was more frequently detected among patients with
      bilateral disease. Production of MGMT was consistent with expression of mRNA. No
      methylation of MGMT promoter was detected in the two retinoblastoma cell lines
      (Y79, WERI-Rb1). CONCLUSIONS: The data show a clear association between impaired
      production of MGMT and hypermethylation of the MGMT promoter, which appeared to
      relate to early onset and poor differentiation, suggesting that epigenetic
      silencing of MGMT by methylation of the promoter and reduced expression of MGMT
      may play an important role in the development and progression of retinoblastoma.

PMID- 11980846
TI  - Foxe3 haploinsufficiency in mice: a model for Peters' anomaly.
AB  - PURPOSE: To evaluate the importance in anterior segment dysgenesis of genetic
      variation in Foxe3, a gene encoding a forkhead transcription factor specifically
      expressed in the lens. METHODS: The phenotype of mice heterozygous for a mutation
      in the DNA-binding domain of Foxe3 was examined from histologic sections, and DNA
      binding by the encoded protein was investigated by gel-shift assay. FOXE3 from
      human patients with Peters' anomaly was PCR amplified and sequenced. RESULTS: The
      dysgenetic lens (dyl) allele of Foxe3 was found to encode a protein unable to
      bind DNA. Approximately 40% of mice heterozygous for Foxe3(dyl) have corneal and
      lenticular defects. The phenotype is variable but typically consists of the
      equivalent of Peters' anomaly in humans, with central corneal opacity,
      keratolenticular adhesion, and, in some cases, anterior polar cataract. In a
      small cohort (n = 13) of patients with Peters' anomaly, shown to be normal in the
      PAX6 locus, one individual was found to be heterozygous for a nonconservative
      missense mutation in FOXE3. The mutation, which does not occur in 116 chromosomes
      from a control population, substitutes leucine for arginine 90 at a highly
      conserved position in the forkhead domain. CONCLUSIONS: Haploinsufficiency of
      Foxe3 in a mouse model causes anterior segment dysgenesis similar to Peters'
      anomaly. Although causality could not be shown in the human case, the presence of
      a rare, nonconservative substitution in FOXE3 of a patient with Peters' anomaly
      is interesting, in light of the phenotypic similarities with the mutant mice.

PMID- 11980847
TI  - Identification of novel mutations causing familial primary congenital glaucoma in
      Indian pedigrees.
AB  - PURPOSE: To determine the possible molecular genetic defect underlying primary
      congenital glaucoma (PCG) in India and to identify the pathogenic mutations
      causing this childhood blindness. METHODS: Twenty-two members of five clinically
      well-characterized consanguineous families were studied. The primary candidate
      gene CYP1B1 was amplified from genomic DNA, sequenced, and analyzed in control
      subjects and patients to identify the disease-causing mutations. RESULTS: Five
      distinct mutations were identified in the coding region of CYP1B1 in eight
      patients of five PCG-affected families, of which three mutations are novel. These
      include a novel homozygous frameshift, compound heterozygous missense, and other
      known mutations. One family showed pseudodominance, whereas others were autosomal
      recessive with full penetrance. In contrast to all known CYP1B1 mutations, the
      newly identified frameshift is of special significance, because all functional
      motifs are missing. This, therefore, represents a rare example of a natural
      functional CYP1B1 knockout, resulting in a null allele (both patients are blind).
      CONCLUSIONS: The molecular mechanism leading to the development of PCG is
      unknown. Because CYP1B1 knockout mice did not show a glaucoma phenotype, the
      functional knockout identified in this study has important implications in
      elucidating the pathogenesis of PCG. Further understanding of how this molecular
      defect leads to PCG could influence the development of specific therapies. This
      is the first study to describe the molecular basis of PCG from the Indian
      subcontinent and has profound and multiple clinical implications in diagnosis,
      genetic counseling, genotype-phenotype correlations and prognosis. Hence, it is a
      step forward in preventing this devastating childhood blindness.

PMID- 11980848
TI  - Induction of VEGF gene expression by retinoic acid through Sp1-binding sites in
      retinoblastoma Y79 cells.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that
      has been implicated in many retinopathies. Although all trans-retinoic acid
      (atRA) has long been known as an essential factor in the visual cycle, the role
      of atRA in the pathogenesis of retinal disease remains elusive. In this study, we
      investigated the effects of atRA on expression of the VEGF gene in retinoblastoma
      Y79 cells. METHODS: Total RNA prepared from Y79 cells, with or without atRA, was
      subjected to Northern blot analyses. Reporter constructs consisting of the VEGF
      promoter-luciferase gene were transfected into Y79 cells. Nuclear factors binding
      to the VEGF promoter were analyzed by electrophoretic mobility shift assays
      (EMSAs). RESULTS: The levels of VEGF transcripts were increased by atRA in a time
      and dose-dependent manner. Progressive deletion and site-specific mutation
      analyses indicated that atRA increased VEGF promoter activity through a G+C-rich
      sequence that was shown to be an Sp1-binding site by supershift assays. EMSAs
      showed that Sp1 binding was increased by atRA stimulation. Although no measurable
      change was observed in Sp1 mRNA levels, Western blot analysis showed an increase
      in Sp1 protein levels in the atRA-treated cells. These data suggest that atRA
      increases Sp1 protein levels by posttranscriptional mechanisms, and elevated
      levels of Sp1 protein induce the expression of VEGF at the transcriptional level.
      CONCLUSIONS: atRA induced transcription of the VEGF gene through Sp1-binding
      sites in Y79 cells. Pharmacologic intervention that inhibits the signals elicited
      by atRA may be effective in treating VEGF-mediated retinopathies.

PMID- 11980849
TI  - Retinoic acid upregulates cone arrestin expression in retinoblastoma cells
      through a Cis element in the distal promoter region.
AB  - PURPOSE: This study was initiated to investigate the molecular mechanisms of
      activation of expression of the human cone arrestin (hCAR) gene by retinoic acid
      (RA), in an in vitro model of retinoblastoma cells. METHODS: Human retinoblastoma
      Weri-Rb-1 or Y79 cell lines were cultured in the absence or presence of RA
      analogues with transcription or translation inhibitors for various periods. The
      mRNAs encoding hCAR, retinoic acid receptor (RAR), and retinoid X receptor (RXR)
      subtypes were analyzed by Northern blot. Immunoblot analysis of hCAR protein was
      also performed. The hCAR promoter's activity and its responsiveness to RA
      treatment was evaluated by transient transfection of the hCAR promotor-luciferase
      reporter constructs, followed by promoter deletion analysis to map the specific
      regions responsible for the RA response. RESULTS: In our in vitro model, both all
      trans RA and 9-cis RA induced hCAR mRNA in a time- and dose-dependent manner.
      RA's effect was blocked by either RNA or protein synthesis inhibitors; however,
      hCAR mRNA's stability was not affected by RA, as determined by RNA decay
      experiments. Although all RAR and RXR subtypes were detected, only RXRgamma and
      RARalpha increased dramatically after treatment with RA. An RXR-specific agonist,
      but not an RAR-specific agonist, also increased hCAR mRNA and protein expression
      in both Weri-Rb-1 and Y79 cells. RA stimulated hCAR promoter-luciferase activity
      in transient transfection studies. Subsequently, a region between -852 and -702
      of the hCAR promoter, with RA-responsive elements (RAREs), was discovered to be
      responsible for the RA response. CONCLUSIONS: The hCAR gene is transcriptionally
      upregulated by RA acting through cis elements within -852 to -702 of the hCAR 5'
      flanking region. Based on the cumulative data, RXRgamma is most likely the RA
      receptor subtype involved in hCAR regulation by RA.

PMID- 11980850
TI  - Site-specific somatic mutagenesis in the retinal pigment epithelium.
AB  - PURPOSE: Generate site-specific somatic mutations selectively in the retinal
      pigment epithelium (RPE) in mice. METHODS: A transgenic mouse line expressing the
      Cre recombinase under the control of the tyrosinase-related protein (TRP)-1
      promoter was generated. The presence of Cre was determined by in situ
      hybridization, and Cre-mediated excision of DNA was analyzed by PCR and alkaline
      phosphatase (AP) histochemistry in reporter mice carrying a loxP-flanked (floxed)
      retinoid X receptor alpha (RXRa) gene and in Z/AP mice, respectively. RESULTS:
      Cre was expressed in the RPE from embryonic day 10.5 to postnatal day 12,
      resulting in efficient floxed excision of DNA in the RPE from embryonic day 10.5
      to adulthood in TRP1-Cre mice. Expressed Cre and excision of DNA were also
      detected in the ciliary margin of the retina and in some cells in the neural
      retina, but not in the embryonic periocular mesenchyme or in the choroid.
      CONCLUSIONS: The TRP1-Cre mouse line, which induces efficient Cre-mediated
      excision of DNA selectively in the RPE, provides a new, powerful tool to study
      gene functions in the RPE in vivo.

PMID- 11980851
TI  - Effect of corneal thickness on intraocular pressure measurements with the
      pneumotonometer, Goldmann applanation tonometer, and Tono-Pen.
AB  - PURPOSE: To compare intraocular pressure (IOP) measurements of the Ocular Blood
      Flow (OBF) pneumotonometer, Goldmann applanation tonometer, and Tono-Pen in eyes
      with normal corneas of various thicknesses. METHODS: IOP was measured with an OBF
      pneumotonometer, Tono-Pen and Goldmann applanation tonometer in random order in
      181 eyes with normal corneas. Central corneal thickness (CCT) was measured using
      an ultrasonic pachymeter after all IOP determinations had been made. Right and
      left eyes were analyzed separately for statistical purposes. RESULTS: With all
      instruments, IOP varied with CCT, even though the variation in IOP was large.
      Readings with the OBF pneumotonometer showed a mean increase in IOP with
      increasing CCT of 0.28 mm Hg/10 microm, an increase of 0.23 mm Hg/10 microm with
      the Goldmann tonometer, and of 0.10 mm Hg/10 microm with the Tono-Pen. The OBF
      pneumotonometer consistently recorded comparatively higher IOPs than the other
      two instruments. CONCLUSIONS: The Tono-Pen is least affected by CCT when used to
      measure IOP in eyes with normal corneas. The OBF pneumotonometer appears to be
      more affected by variation in CCT than the Goldmann tonometer. This is contrary
      to expectations, based on the mechanism of measurement of IOP of the OBF
      pneumotonometer.

PMID- 11980852
TI  - Elevated vernier acuity thresholds in glaucoma.
AB  - PURPOSE: In 1993, Piltz et al. observed that foveal vernier acuity thresholds for
      achromatic targets are elevated in patients with glaucoma. This study was
      undertaken to explore whether such elevated thresholds are present when subject
      groups are measured with targets of effectively equivalent contrast. Vernier
      acuity measures were also obtained with short-wavelength and frequency-doubled
      stimuli, to assess spatial hyperacuity performance in the short-wavelength
      sensitive and magnocellular pathways, respectively. METHODS: Twenty patients with
      glaucoma and 19 subjects with normal vision participated. All subjects had visual
      acuity of 20/25 or better. Achromatic two-dot vernier thresholds were obtained
      for 90% contrast dots. In addition, individual contrast thresholds to the
      achromatic dots were measured for each subject, and vernier thresholds were
      measured at 4, 8, 12, and 16 times contrast threshold. Short-wavelength vernier
      acuity thresholds were measured for blue dots presented on a bright yellow
      background. The stimulus for the frequency-doubling grating vernier acuity task
      was a 90% contrast, 1-cyc/deg, 25-Hz sinusoidal grating. RESULTS: The glaucoma
      group demonstrated significantly higher foveal vernier acuity thresholds than
      control subjects for the blue-on-yellow stimulus (P = 0.002) and frequency
      doubling grating stimulus (P < 0.001). No significant difference in vernier
      acuity between groups was found for the 90% contrast achromatic dots (P = 0.09),
      however a significant difference was found for the normalized contrast targets (P
      = 0.04). CONCLUSIONS: Vernier acuity tasks can be used to demonstrate abnormal
      foveal function in glaucoma. Testing with visual-function-specific stimuli may be
      effective in identifying such dysfunction. Vernier acuity, or other similar
      hyperacuity tasks that assess spatial sampling, may be useful in the detection of
      early glaucomatous damage, before it is detected with traditional perimetric
      tests.

PMID- 11980853
TI  - Examination of different pointwise linear regression methods for determining
      visual field progression.
AB  - PURPOSE: To compare the specificity and sensitivity of several different methods
      for using pointwise linear regression (PLR) to detect progression (deterioration)
      in visual fields. METHODS: First, theoretical results were derived to predict
      which of the considered PLR methods would be the most specific and hence the
      least sensitive. Then, a "Virtual Eye" simulation model was developed that
      simulates series of sensitivity readings for a point over time. The model adds
      normally distributed noise (estimated from published results) to the sensitivity
      at each point to produce a series of fields to be analyzed using each method.
      Stable and deteriorating eyes were simulated, with the latter defined to have a
      noise-free loss of 2 dB/y at a significant cluster of points over the series.
      RESULTS: The most sensitive method tested was to flag a visual field as
      progressing if it had a point that exhibited a statistically significant slope
      (at the 1% level) of at least -1 dB/y in the sensitivity. The most specific was a
      new "Three-Omitting" method that is being proposed, using two confirmation fields
      in a novel way. Current methods of using confirmation fields to verify a
      significant slope incorrectly flagged up to twice as many stable eyes as having
      progressing fields as did our new method. CONCLUSIONS: Using the new proposed PLR
      method is recommended in preference to current PLR methods in any applications
      when a high degree of specificity is the main priority.

PMID- 11980854
TI  - Height and its relationship to refraction and biometry parameters in Singapore
      Chinese children.
AB  - PURPOSE: To examine the association between the anthropometric measurements of
      height, weight, body mass index (BMI) and refraction and other ocular parameters
      in Singapore Chinese children. METHODS: In a cross-sectional study of 1449
      Chinese schoolchildren, aged 7 to 9 years, from three Singapore schools, height
      and weight were measured according to standard protocol, and BMI was calculated.
      Refractive error and corneal curvature measures were determined by autorefraction
      in eyes under cycloplegia. Axial length, vitreous chamber depth, lens thickness,
      and anterior chamber depth were measured using A-scan biometry ultrasonography.
      RESULTS: In comparison with the children with height in the first quartile for a
      given age and gender, the eyeball length in children in the fourth quartile was
      0.46 mm longer, the vitreous chamber depth 0.46 mm deeper, the corneal radius of
      curvature 0.10 mm greater (i.e., flatter), refraction more negative by 0.47 D (
      0.76 D versus -0.29 D), and axial length-to-corneal curvature radius (AL-CR)
      ratio higher, after analyses controlling for age, gender, parental myopia,
      reading, school, and weight. The associations of height with refractive error and
      AL-CR ratio were significant in girls but not in boys. Heavier and more obese
      children had refractions that were more hyperopic (P = 0.01, P = 0.08), after
      analyses controlling for age, gender, parental myopia, reading, and school
      (height was also controlled for if weight was evaluated). This association was
      present in boys but not in girls. CONCLUSIONS: Controlling for age, gender,
      parental myopia, reading, school, and weight showed that taller Singapore Chinese
      children had eyes with longer axial lengths, deeper vitreous chambers, flatter
      corneas, and refractions that tended toward myopia. In multivariate analysis,
      eyes in children who were heavier or who had a higher BMI tended to have
      refractions that were more hyperopic, and eyes in heavier children had shorter
      vitreous chambers. Differences between the present results and a recent report in
      Singapore adults suggest either a cohort effect or a potential influence of
      systemic endocrine or metabolic factors during childhood on refractive
      development.

PMID- 11980855
TI  - Corneal expression of the inflammatory mediator CAP37.
AB  - PURPOSE: CAP37 is a polymorphonuclear neutrophil (PMN)-derived inflammatory
      protein with potent antibiotic and chemotactic activity. To further investigate
      the biological significance of CAP37 in infection and inflammation, a well
      characterized in vivo rabbit model of bacterial keratitis was selected to study
      its contribution to host defenses. METHODS: One hundred colony-forming units of
      log phase Staphylococcus aureus was injected intrastromally. Eyes were enucleated
      at 5 to 25 hours after infection and CAP37 detected by immunohistochemistry. To
      identify the mechanism of CAP37 upregulation in corneal epithelium, in vitro
      studies using immortalized human corneal epithelial cells (HCECs) were undertaken
      to determine whether proinflammatory cytokines, such as tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta), induce CAP37. Because
      adhesion of leukocytes is important in leukocyte-epithelium interactions, the
      effect of CAP37 on expression of intercellular adhesion molecule (ICAM)-1 on
      HCECs was determined by flow cytometry. RESULTS: Strong staining for CAP37 was
      demonstrated in the corneal epithelium, stromal fibroblasts, ciliary epithelium,
      related limbus, ciliary vascular endothelium, and bulbar conjunctiva in rabbits
      injected with S. aureus. The most dramatic expression of CAP37 aside from that in
      the PMNs occurred in the corneal epithelium. The in vitro studies suggest that
      CAP37 induction is regulated by TNF-alpha and IL-1beta. In addition, ICAM-1
      expression on HCECs was increased in response to CAP37. Molecular cloning of
      corneal epithelial CAP37 indicated strong sequence identity with an extensive
      region of PMN-CAP37. CONCLUSIONS: The findings in this study describe the
      extraneutrophilic expression of CAP37 in response to infection and suggest a role
      for CAP37 in host defense against infection in the eye.

PMID- 11980856
TI  - Delay of corneal epithelial wound healing and induction of keratocyte apoptosis
      by platelet-activating factor.
AB  - PURPOSE: To examine the role of the lipid mediator platelet-activating factor
      (PAF) in epithelial wound healing. METHODS: A 7-mm central de-epithelializing
      wound was produced in rabbit corneas, and the tissue was incubated with 125 nM
      carbamyl PAF (cPAF), an analogue of PAF. Rabbit corneal epithelial and stromal
      cells were also cultured in the presence of cPAF. Cell adhesion, proliferation,
      and migration assays were conducted. Apoptosis was assayed by TUNEL staining on
      preparations of corneal tissue sections and in cells in culture. RESULTS: Twenty
      four hours after injury, 50% of the wounded area was covered by new epithelium,
      whereas only 30% was covered in the presence of cPAF. At 48 hours, the epithelium
      completely closed the wound, but only 45% of the original wound was covered in
      corneas treated with cPAF. Similar inhibition of epithelial wound closure was
      found with human corneas incubated with PAF in organ culture. Moreover, addition
      of several growth factors involved in corneal wound healing, such as epidermal
      growth factor, hepatocyte growth factor, and keratinocyte growth factor, could
      not overcome the inhibitory action of PAF in wound closure. Three PAF
      antagonists, BN50727, BN50730, and BN50739, abolished the effect of PAF. A
      significant increase in TUNEL-positive staining occurred in corneal stromal cells
      (keratocytes), which was inhibited by preincubating the corneas with PAF
      antagonists. However, no TUNEL-positive staining was found in epithelial cells.
      TUNEL-staining results in cultured stromal cells (keratocytes) and epithelial
      cells in first-passage cell culture were similar to those in organ-cultured
      corneas. In addition, PAF caused 35% to 56% inhibition of adhesion of epithelial
      cells to proteins of the extracellular matrix: collagen I and IV, fibronectin,
      and laminin. There were no significant changes in proliferation or migration of
      epithelial cells induced by the lipid mediator. CONCLUSIONS: The results suggest
      PAF plays an important role in preventing corneal wound healing by affecting
      adhesion of epithelial cells and increasing apoptosis in stromal cells. PAF
      antagonists could be of therapeutic importance during prolonged ocular
      inflammation, helping to avoid loss of corneal transparency and visual acuity.

PMID- 11980858
TI  - Pseudomonas aeruginosa exotoxin A and keratitis in mice.
AB  - PURPOSE: To determine the importance of Pseudomonas aeruginosa exotoxin A (ETA)
      as a virulence factor in corneal disease. METHODS: Isogenic mutants deficient in
      ETA were constructed in P. aeruginosa strains PAO1 and ATCC 19660 by allelic
      exchange and then evaluated for virulence in a mouse model of bacterial
      keratitis. The effect of ETA on adherence to scarified corneal epithelium was
      assessed in an in vitro organ culture model. RESULTS: Mutants of either P.
      aeruginosa PAO1 or 19660, deficient in ETA, adhered to wounded corneal tissue and
      initiated ocular disease similar to that in wild-type strains. However, in
      contrast to wild-type strains, ETA mutants were quickly cleared from the eye,
      inflammation diminished, and the cornea healed. CONCLUSIONS: Although ETA has no
      effect on the ability of P. aeruginosa to adhere to corneal wounds or to initiate
      Pseudomonas keratitis, it is crucial for the organism to persist in the eye and
      ultimately cause disease.

PMID- 11980859
TI  - Volume estimation of excimer laser tissue ablation for correction of spherical
      myopia and hyperopia.
AB  - PURPOSE: To determine the theoretical volumes of ablation for the laser treatment
      of spherical refractive errors in myopia and hyperopia. METHODS: The cornea was
      modeled as a spherical shell. The ablation profiles for myopia and hyperopia were
      based on an established paraxial formula. The theoretical volumes of the ablated
      corneal lenticules for the correction of myopia and hyperopia were calculated by
      two methods: (1) mathematical approximation based on a simplified geometric model
      and (2) finite integration. These results were then compared for optical zone
      diameters of 0.5 to 11.00 mm and for initial radii of curvature of 7.5, 7.8, and
      8.1 mm. RESULTS: Referring to a simplified geometrical model, the volume of
      ablated corneal tissue was estimated to be proportional to the magnitude of
      treatment (D) and to the fourth power of the treatment diameter (S(4)). For
      refractive correction of myopia and hyperopia, volume estimations using our
      formula, V congruent with D. (S/9)(4), were similar to those obtained by finite
      integration for optical zone diameters of 0.5 to 8.5 mm and for corneal radii of
      curvature within the clinical range (7.5, 7.8, and 8.1 mm). CONCLUSIONS: The
      theoretical volume of corneal tissue ablated within the optical zone for
      spherical corrections can be accurately approximated by this simplified formula.
      This may be helpful in evaluating factors that contribute to corneal ectasia
      after LASIK for myopia and hyperopia. Treatment diameter (S) is the most
      important determinant of the volume of tissue ablation during excimer laser
      surgery.

PMID- 11980857
TI  - Role of proinflammatory cytokines in the impaired lacrimation associated with
      autoimmune xerophthalmia.
AB  - PURPOSE: To determine the effects of the proinflammatory cytokines interleukin
      (IL)-1alpha, IL-1beta, and tumor necrosis factor (TNF)-alpha on neurally mediated
      lacrimal gland protein secretion and to determine whether the amount of IL-1beta
      protein is upregulated in inflamed lacrimal glands of the MRL/lpr mouse, a murine
      model of human Sjogren syndrome. METHODS: Lacrimal gland lobules of BALB/c mice
      were prepared and incubated for 2 hours in the presence or absence of recombinant
      human (rh)IL-1alpha, rhIL-1beta (10 ng/mL each), or rhTNFalpha (50 ng/mL).
      Peroxidase secretion in response to depolarizing KCl (75 mM) solution was
      measured by spectrofluorometric assay. In another set of experiments, saline,
      rhIL-1beta (1 microg), or an antibody against IL-1 receptor type I (IL-1RI), with
      or without rhIL-1beta, was injected (2 microL) into the lacrimal glands of
      anesthetized BALB/c mice. Twenty-four hours later, lacrimal gland lobules were
      prepared and peroxidase secretion was measured. The amount of IL-1beta protein in
      lacrimal gland acinar cell lysates prepared from 3-, 9-, and 13-week-old BALB/c,
      MRL/(+), and MRL/lpr mice was determined by ELISA. RESULTS: KCl-induced
      peroxidase secretion was inhibited in vitro 62%, 66%, and 53% by rhIL-1alpha,
      rhIL-1beta, and rhTNFalpha, respectively. In vivo, rhIL-1beta inhibited KCl
      induced peroxidase secretion by 72%. This inhibitory effect of IL-1beta was
      completely reversed by an antibody against IL-1RI. Compared with 3-week-old mice,
      the amount of IL-1beta protein was upregulated 15- and 21-fold in lacrimal gland
      acinar cells isolated from 9- and 13-week-old MRL/lpr mice, respectively.
      CONCLUSIONS: Proinflammatory cytokines inhibit neurally mediated lacrimal gland
      secretion. The amount of IL-1beta protein is upregulated in acinar cells prepared
      from lacrimal glands infiltrated with lymphocytes. These results suggest that
      elevated levels of IL-1beta, as they occur in Sjogren syndrome exocrine glands,
      may impair the secretory function of these tissues.

PMID- 11980860
TI  - Fundus photography for measurement of macular pigment density distribution in
      children.
AB  - PURPOSE: To evaluate a photographic procedure for reflectometry of the
      topographic distribution of macular pigment density in normal pediatric subjects.
      METHODS: Digitized blue (480 nm) and green (540 nm) photographic images were
      aligned and subtracted to generate optical density difference maps. An 8 degrees
      x 8 degrees area concentric with the fovea was analyzed. Gaussian curves were
      fitted through the foveola along the vertical and horizontal meridians. The peak
      density and full widths at half maximum (FWHMs) were calculated. The subjects (n
      = 23; median age 10.5 years) had normal eyes and good acuity. RESULTS: The peak
      macular pigment (MP) density was 0.13 +/- 0.04 density units (DU) which is at the
      lower end of the range previously obtained by other reflectometry procedures.
      Density distributions were circularly symmetrical. The FWHM ranged was 2.4
      degrees +/- 0.5 degrees. Neither MP nor FWHM varied significantly with age.
      CONCLUSIONS: The photographic method is feasible and provides quantitative
      assessment of topographic properties of macular pigment in young subjects. Future
      application to clinical studies of pediatric patients is envisioned.

PMID- 11980861
TI  - Topical flunarizine reduces IOP and protects the retina against ischemia
      excitotoxicity.
AB  - PURPOSE: To determine whether topical application of flunarizine reduces
      intraocular pressure (IOP) and acts as a retinal neuroprotectant and to compare
      the effectiveness of flunarizine with betaxolol and nifedipine at reducing the
      influx of calcium and sodium. METHODS: Ischemia was delivered to the rabbit
      retina by raising the IOP. After 3 days, a flash electroretinogram (ERG) was
      recorded, and the retina processed for the localization of certain antigens. In
      the rat, N-methyl-D-aspartate (NMDA) was injected intravitreally, and 8 days
      later, the retinas were analyzed for the localization of Thy-1 or the relative
      amounts of mRNAs for antigens located to ganglion cells or photoreceptors. Rats
      and rabbits received topical flunarizine or vehicle before and after ischemia or
      NMDA. IOP was measured in rabbits after a single topical application of 2%
      flunarizine. Studies were conducted on isolated rat retinas, cortical cultures,
      and brain synaptosomes to compare the effectiveness of flunarizine with
      nifedipine and betaxolol at reducing the influx of calcium or sodium. RESULTS:
      Changes in rabbit retinal choline acetyltransferase and parvalbumin
      immunoreactivities and the b-wave of the ERG caused by ischemia-reperfusion were
      blunted by topical treatment with flunarizine. Similarly, NMDA induced reductions
      in Thy-1 immunoreactivity and mRNA for rat ganglion cell antigens (Thy-1 and
      neurofilament light form) were counteracted by topical application of
      flunarizine. Topical application of 2% flunarizine significantly lowered the IOP
      in rabbits over a period of 5 hours. Flunarizine was more effective than
      betaxolol and much stronger than nifedipine at attenuating veratridine-induced
      influx of sodium into synaptosomes. Nifedipine, flunarizine, and betaxolol all
      reduced the NMDA-induced influx of calcium into the isolated retina or cortical
      neurons, but betaxolol was the least effective. CONCLUSIONS: Topically applied
      flunarizine reduces IOP and attenuates injury to the whole of the retina,
      including the ganglion cells. The neuroprotective action of flunarizine is to
      reduce the influx of calcium and sodium into stressed neurons. The potent effect
      of flunarizine on sodium influx would be particularly protective to axons.

PMID- 11980862
TI  - Correction for the erroneous compensation of anterior segment birefringence with
      the scanning laser polarimeter for glaucoma diagnosis.
AB  - PURPOSE: To evaluate whether erroneous compensation for anterior segment
      retardation can be estimated and used to correct peripapillary (PP) retinal nerve
      fiber layer (RNFL) retardation measurements. METHODS: Retardation measurements
      (for the 780-nm wavelength), given as RNFL thickness by the scanning laser
      polarimeter, were obtained at the macula and PP retina in 45 eyes of 45 normal
      subjects and 53 eyes of 53 patients with early glaucoma. The correlation of
      macula and PP retardation was assessed. The normal range for RNFL retardation was
      defined as 97.5th minus 2.5th percentile (normal subjects). This was calculated
      for uncorrected PP RNFL retardation and for PP RNFL retardation corrected by
      retardation measurements taken in the macula (analysis 1) and in the temporal
      aspect of the PP measurement annulus (analysis 2). Further ranges were defined at
      different percentile cutoffs, and normal and glaucomatous eyes were classified as
      abnormal if retardation measurements were below each cutoff. The accuracy of
      classification by uncorrected and corrected measurements was assessed by receiver
      operating characteristic curve analysis. Uncorrected and corrected RNFL
      retardation was correlated with visual field mean deviation (MD). RESULTS: PP
      retardation correlated significantly with of macular retardation in normal (r(2)
      = 0.71, P < 0.000) and glaucomatous (r(2) = 0.41, P < 0.000) eyes. The normal
      range for uncorrected PP retardation was 25.4 degrees and for corrected
      retardation, 18.0 degrees (analysis 1) and 14.6 degrees (analysis 2), a reduction
      of 29% and 43%, respectively. For a specificity of 85%, the sensitivity to
      identify glaucomatous eyes of uncorrected and corrected (analyses 1 and 2)
      retardation was 26%, 55%, and 66%, respectively. Corrected PP retardation
      measurements correlated better with visual field MD (analysis 1: r(2) = 0.21;
      analysis 2: r(2) = 0.18) than did uncorrected measurements (r(2) = 0.05).
      CONCLUSIONS: Erroneously corrected anterior segment birefringence significantly
      affects PP RNFL retardation measurements. Retardation arising from the cornea
      corneal compensator interaction can be partially estimated from the macula and
      temporal aspect of the PP measurement annulus, allowing correction of PP RNFL
      retardation. This provides a narrower normal range and greater sensitivity for
      glaucoma diagnosis.

PMID- 11980863
TI  - Expression and localization of FP and EP prostanoid receptor subtypes in human
      ocular tissues.
AB  - PURPOSE: To determine the expression and precise cellular and subcellular
      localization of the EP prostanoid receptor subtypes EP(1) through EP(4) and the
      FP receptor in normal human ocular tissues on the protein and mRNA levels.
      METHODS: Expression of EP and FP receptor proteins was examined by
      immunohistochemistry on the light microscopic level, using subtype-specific
      antibodies on frozen and paraffin-embedded tissue sections of 10 normal human
      donor eyes. The subcellular distribution of the receptor proteins was studied by
      electron microscopic immunogold labeling. mRNA expression in various ocular
      tissues was analyzed by reverse transcription-polymerase chain reaction, using
      subtype-specific primers. RESULTS: The highest expression of the EP(1) receptor
      protein was found in the epithelia of the cornea, conjunctiva, lens, and the
      ciliary body; trabecular cells; iris vessels; and retinal ganglion cells. EP(2)
      receptor labeling was most prominent in the corneal epithelium and
      choriocapillaries. EP(3) and EP(4) receptor labeling was primarily observed in
      the corneal endothelium and keratocytes, trabecular cells, ciliary epithelium,
      and conjunctival and iridal stroma cells, and EP(3) was found, in addition, in
      retinal Muller cells. The highest expression of FP receptor protein was found in
      the corneal epithelium, ciliary epithelium, the circular portion of ciliary
      muscle, and iris stromal and smooth muscle cells. Immunoelectron microscopy
      showed a subcellular distribution of all prostanoid receptors along plasma
      membranes and the nuclear envelope. EP and FP receptor mRNA expression largely
      paralleled the proteins' expression patterns. CONCLUSIONS: The findings
      demonstrate a wide distribution but differential expression of FP and EP
      prostanoid receptor subtypes in human ocular tissues. EP(1) through EP(4)
      receptor subtype expression in human outflow pathways could be significant for
      future pharmacologic management strategies for the glaucomas.

PMID- 11980864
TI  - Immune cells in the porcine retina: distribution, characterization and
      morphological features.
AB  - PURPOSE: To investigate the presence of immunocompetent cells in the porcine
      retina and to compare the findings with those obtained earlier in human retinas.
      METHODS: Retinal wholemounts or cryostat sections from outbred Dutch Landrace
      pigs were analyzed for the presence of microglia (CD45), macrophages-monocytes
      (SW3, CD163, 2A10, CD14), major histocompatibility complex (MHC) class II
      positive cells (MCA1335), granulocytes (MCA1219), B lymphocytes (IgM), and T
      lymphocytes (CD6, CD4, CD8), by using specific monoclonal antibodies followed by
      immunohistochemical staining. RESULTS: A uniform distribution of CD45-positive
      microglial cells was observed throughout the porcine retina (mean number, 289 +/-
      16 cells/mm(2)). The microglia were observed along blood vessels and within the
      tissue between the inner limiting membrane and the inner nuclear layer. MHC class
      II-positive cells were mainly observed along the large- and middle-sized retinal
      blood vessels. Double-staining experiments showed that 54% of the microglial
      cells lining the larger retinal vessels were MHC class II positive. Macrophages
      were only incidentally observed along the larger retinal blood vessels. No T
      lymphocytes, B lymphocytes, monocytes, or granulocytes were observed within the
      retinal tissue. CONCLUSIONS: The porcine retina contains a rich network of
      microglial cells. Approximately half of the microglial cells lining the larger
      retinal vessels express MHC class II. The normal porcine retina is devoid of
      lymphocytes, monocytes, and granulocytes. The distribution of immunocompetent
      cells in the porcine retina largely resembles that observed in the human retina.

PMID- 11980865
TI  - MCP-1 expression in endotoxin-induced uveitis.
AB  - PURPOSE: Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with
      chemoattractant properties for monocytes, memory T cells, natural killer cells,
      mast cells, and basophils. To delineate the role played by MCP-1 in acute
      anterior uveitis, a common ocular inflammation, MCP-1(-/-) mice and wild-type
      matched control mice were analyzed for the development of endotoxin-induced
      uveitis (EIU) in response to subcutaneous injection of a sublethal dose of
      lipopolysaccharide (LPS). METHODS: EIU was induced in MCP-1(-/-) and wild-type
      control mice by a single subcutaneous injection of Salmonella typhimurium LPS
      endotoxin at day 0. Alternatively, MCP-1(-/-) mice were injected subcutaneously
      with LPS plus recombinant MCP-1 at day 0 and with recombinant MCP-1 6 hours
      later. Mice were killed at day 1 or 3 after injection. Serum levels of IL-1alpha,
      IL-1beta, IL-6, IFN-gamma, TNF-alpha, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), macrophage inflammatory protein (MIP)-1alpha, MIP-2, regulated
      on activation normal T-cell expressed and secreted (RANTES), and MCP-1 were
      determined by ELISA. Eyes were collected and analyzed histologically and by RT
      PCR for MCP-1, IFN-gamma, IL-6, TNF-alpha, beta-actin, MCP-5, RANTES, KC,
      inflammatory protein (IP)-10, and toll-like receptor (TLR)-4. RESULTS: EIU was
      strongly reduced in MCP-1(-/-) mice compared with wild-type control mice. The
      number of ocular inflammatory cells was significantly reduced. Moreover,
      intraocular IFN-gamma transcription was increased. EIU was induced in MCP-1(-/-)
      mice by co-administration of recombinant rat MCP-1 and LPS. CONCLUSIONS: Data
      indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a
      new therapeutic strategy for acute anterior uveitis.

PMID- 11980866
TI  - Phenotypes of T cells infiltrating the eyes in autoimmune anterior uveitis
      associated with EAE.
AB  - PURPOSE: Lewis rats immunized with myelin basic protein (MBP) develop
      experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis
      (AU), which recurs. The goal was to analyze cellular activation markers and
      adhesion molecules of T cells that infiltrate the eyes and spinal cord during
      acute and recurrent AU in actively and passively induced diseases simultaneously
      in the same animals. METHODS: EAE-AU was induced in Lewis rats by immunization
      with MBP in CFA, or by adoptive transfer of MBP-specific T-cell lines, and the
      signs of clinical EAE and AU was scored. Cells isolated from the iris-ciliary
      body were tested by flow cytometry for expression of CD4, CD8, CD45RC, T-cell
      receptor (TCR) Vbeta8.2, alpha4 integrin, L-selectin, CD44, and CD134. RESULTS:
      Ocular T cells showed a significantly higher expression of CD62L (l-selectin)
      than did T cells in the spinal cord. In addition, a much lower percentage of
      infiltrating CD8(+) T cells was found in the eyes during AU. In passive transfer
      experiments, T-cell lines derived from acute and recurrent uveitis showing
      similar phenotypes differing in specificities but possessed the capacity of
      inducing both AU and EAE. Pretreatment of rats with effector CD4(+) T cell before
      MBP immunization did not induce suppression of EAE or AU. However, pretreatment
      with regulatory CD8(+) T cells significantly reduced the severity and duration of
      both EAE and AU. CONCLUSIONS: T cells recruited into the inflamed eyes or central
      nervous system (CNS) are mainly activated/memory T cells expressing different
      levels of L-selectin. Regulatory CD8(+) T cells may contribute to the
      susceptibility of the eye to recurrent AU. The differences in phenotypes of T
      cells recruited simultaneously to two different organs suggest that
      microenvironment also plays a role in determining lymphocyte homing.

PMID- 11980867
TI  - Unique roles for E2F1 in the mouse lens in the absence of functional pRB
      proteins.
AB  - PURPOSE: Normal lens fiber cell differentiation requires functional
      retinoblastoma protein (pRB), because inactivation of this protein results in
      proliferation and apoptosis in normally postmitotic, differentiating fiber cells.
      Loss of either E2F1 or -3 can partially rescue the lens phenotype in Rb-deficient
      mice, implying that these E2Fs may have specific targets in this system. The
      purpose of this study was to determine what unique role E2F1 may play. METHODS:
      Expression of E2F family members and target genes was analyzed in the lenses of
      nontransgenic, E2F1-null, alphaAE7;E2F1-sufficient; and alphaAE7;E2F1-null mice
      by in situ hybridization, Northern blot analysis, and RT-PCR. RESULTS: In lenses
      of E2F1-null mice, there was no change in the expression of E2F-2 to -5 or their
      target genes, compared with E2F1-sufficient mice. However, in the lens of
      alphaAE7 mice where pRB proteins are inactivated, expression of E2F2 and -3a was
      increased. The E2F3a increase, but not that of E2F2, was dependent on E2F1.
      Expression of E2F target genes was increased with expression of E7 and expression
      of one of these, p19ARF, was E2F1 dependent. CONCLUSIONS: Although in the normal
      lens there do not appear to be unique roles for E2F1 that cannot be fulfilled by
      other E2F family members, in the absence of functional pRB proteins, E2F1 is
      specifically responsible for the increased expression of E2F3a and p19ARF. These
      findings suggest that E2F1 may be the preferred E2F regulating these target genes
      in the normal lens.

PMID- 11980868
TI  - Altered Na,K-ATPase pattern in gamma-crystallin mutant mice.
AB  - PURPOSE: Na,K-adenosine triphosphatase (ATPase) activity is elevated in the
      lenses of murine cataract Cryge(t) and Cryge(ns) mutant mice. In the present
      study, the expression of Na,K-ATPase alpha1, alpha2, and alpha3 catalytic subunit
      polypeptides was examined in the lenses of these mutant mice. METHODS: Membrane
      material was isolated from lenses and brain of 3-week-old wild-type mice, as well
      as heterozygous and homozygous mutant mice. Microsomal membranes were prepared by
      centrifugation of the homogenized material, and Na,K-ATPase polypeptides were
      detected by immunoblot analysis with antibodies directed against the Na,K-ATPase
      isoforms alpha1, alpha2, and alpha3. RESULTS: For the Na,K-ATPase isoforms alpha2
      and alpha3, membrane material obtained from the homozygous cataract mutants
      showed dense immunoblot bands that were not detected in material obtained from
      wild-type mice. An apparent increase of the alpha1 Na,K-ATPase isoform band
      density was also detected in lens material from the homozygous mutant mice. The
      Na,K-ATPase alpha3 polypeptide was also detected in lens membrane material
      obtained from heterozygous mice of both mutant strains. The alpha2 Na,K-ATPase
      polypeptide was observed in lens membrane material obtained from heterozygous
      Cryge(t) mice, and a less dense band was detected in heterozygous Cryge(ns) mice.
      Band densities of Na,K-ATPase subunits alpha1, alpha2, and alpha3 detected in
      brain membrane material were similar in both mutant and wild-type mice.
      CONCLUSIONS: The immunoblot results suggest that the abundance of Na,K-ATPase
      polypeptide is increased in the lens of the cataract mouse mutant but is not
      altered in the brain. The expression of the alpha2 and alpha3 isoform proteins of
      Na,K-ATPase is markedly upregulated in the cataractous lens.

PMID- 11980869
TI  - Effects of granulocyte colony stimulating factor on retinal leukocyte and
      erythrocyte flux in the human retina.
AB  - PURPOSE: The blue-field entoptic technique was introduced more than 20 years ago
      to quantify perimacular white blood cell flux. However, a final confirmation that
      the perceived corpuscles represent leukocytes is still unavailable. METHODS: The
      study design was randomized, placebo-controlled, and double masked with two
      parallel groups. Fifteen healthy male subjects received a single dose of
      granulocyte colony stimulating factor (G-CSF, 300 microg) and 15 other subjects
      received placebo. The following parameters were assessed at baseline and at 12
      minutes and 8 hours after administration: retinal white blood cell flux, with the
      blue-field entoptic technique; retinal blood velocities, with bidirectional laser
      Doppler velocimetry; retinal venous diameter determined with a retinal vessel
      analyzer; and blood pressure and pulse rate determined by automated oscillometry
      and pulse oxymetry, respectively. RESULTS: After 12 minutes, G-CSF reduced total
      leukocyte count from 5.5 +/- 1.4 10(9)/L at baseline to 1.9 +/- 0.4 10(9)/L. This
      was paralleled by a 35% +/- 11% decrease in retinal white blood cell density.
      After 8 hours G-CSF increased total leukocyte counts to 20.0 +/- 4.4 10(9)/L.
      Again, this increase in circulating leukocytes was reflected by an increase in
      retinal white blood cell density (110% +/- 48%). All effects were significant at
      P < 0.001. By contrast, none of the other hemodynamic parameters was changed by
      administration of G-CSF. CONCLUSIONS: The results clearly indicate that the blue
      field entoptic technique assesses leukocyte movement in the perimacular
      capillaries of the retina. Moreover, white blood cell density appears to
      adequately reflect the number of circulating leukocytes within the retinal
      microvasculature. Hence, an increase in retinal white blood cell density does not
      necessarily reflect retinal vasodilatation.

PMID- 11980870
TI  - Protein tyrosine kinase and protein phosphatase signaling pathways regulate
      volume-sensitive chloride currents in a nonpigmented ciliary epithelial cell
      line.
AB  - PURPOSE: To investigate whether signaling pathways that incorporate protein
      tyrosine kinases and phosphatases regulate PKC-sensitive, volume-sensitive Cl(-)
      currents (I(Cl,vol)) in cultured rabbit nonpigmented ciliary epithelial cells.
      METHODS: Activation of I(Cl,vol) in response to hyposmotic stimulation was
      recorded with whole-cell patch-clamp techniques in the presence of pharmacologic
      agents that activate or block kinases and phosphatases. RESULTS: I(Cl,vol) in
      rabbit nonpigmented ciliary epithelial cells was identified as a PKC-sensitive,
      volume-sensitive Cl(-) current, because current was downregulated during cell
      swelling by phorbol-12-dibutyrate, a PKC activator, and the PKC inhibitors,
      calphostin and chelerythrine, enhanced the current. Activation of c-Src tyrosine
      kinases, with an Src activator peptide (EPQ(pY)EEIPI), increased I(Cl,vol) after
      hyposmotic stimulation, whereas the protein tyrosine kinase inhibitor, genistein,
      but not its inactive analogue daidzein, inhibited the current. The
      phosphatidylinositol-3-kinase (PI3K) inhibitor, wortmannin, inhibited I(Cl,vol).
      Wortmannin did not further inhibit I(Cl,vol) in cells pretreated with the protein
      tyrosine kinase inhibitor, genistein, but blocked enhancement of I(Cl,vol) by PKC
      inhibitors. The serine-threonine protein phosphatase (PP) inhibitor, okadaic
      acid, blocked activation of I(Cl,vol), whereas insulin, which activates PI3K and
      PP-1, enhanced the current. The insulin-enhanced current was also blocked by
      okadaic acid. I(Cl,vol) was not activated under isosmotic conditions by the
      simultaneous inhibition of PKC with calphostin and activation of PP-1 by insulin.
      CONCLUSIONS: These data show that PKC-sensitive Cl(-) currents activated in
      response to cell swelling in nonpigmented ciliary epithelial cells are modulated
      by protein tyrosine kinase, PI3K, and PP signaling pathways. Activation of PP and
      PKC may involve the upstream intermediaries Src tyrosine kinase and PI3K.

PMID- 11980871
TI  - Evaluation of a novel biomaterial in the suprachoroidal space of the rabbit eye.
AB  - PURPOSE: Drug delivery to treat diseases of the posterior segment of the eye,
      such as choroidal neovascularization and its complications, is hampered by poor
      intraocular penetration and rapid elimination of the drug from the eye. The
      purpose of this study was to investigate the feasibility and tolerance of
      suprachoroidal injections of poly(ortho ester) (POE), a bioerodible and
      biocompatible polymer, as a biomaterial potentially useful for development of
      sustained drug delivery systems. METHODS: After tunnelization of the sclera,
      different formulations based on POE were injected (100 microL) into the
      suprachoroidal space of pigmented rabbits and compared with 1% sodium
      hyaluronate. Follow-up consisted of fundus observations, echography, fluorescein
      angiography, and histologic analysis over 3 weeks. RESULTS: After injection, POE
      spread in the suprachoroidal space at the posterior pole. It was well tolerated
      and progressively disappeared from the site of injection without sequelae. No
      bleeding or retinal detachment occurred. Echographic pictures showed that the
      material was present in the suprachoroidal space for 3 weeks. Angiography
      revealed minor pigment irregularities at the site of injection, but no retinal
      edema or necrosis. Histology showed that POE was well tolerated in the choroid.
      CONCLUSIONS: POE suprachoroidal injections, an easy, controllable, and
      reproducible procedure, were well tolerated in the rabbit eye. POE appears to be
      a promising biomaterial to deliver drugs focally to the choroid and the retina.

PMID- 11980872
TI  - Focal macular electroretinograms before and after removal of choroidal
      neovascular lesions.
AB  - PURPOSE: To evaluate the changes in focal macular electroretinograms (fmERGs)
      after surgical removal of choroidal neovascular (CNV) lesions. METHODS: Fourteen
      patients (14 eyes) with subfoveal or juxtafoveal CNV associated with age-related
      macular degeneration and 1 patient with idiopathic CNV underwent vitrectomy and
      removal of the lesions. fmERGs elicited by a 15 degree stimulus were recorded
      before and 3 months after surgery. Optical coherence tomography (OCT) was
      performed to measure the foveal and parafoveal thickness before and 3 months
      after surgery. RESULTS: Preoperative fmERGs were markedly reduced in all eyes.
      The mean amplitude of the b-wave in 15 eyes recorded 3 months after surgery
      increased significantly (P = 0.0022, Wilcoxon signed rank test). In all eyes
      except two with nearly nonrecordable a- and b- waves, the mean b-wave-to-a-wave
      ratio after surgery increased significantly in all eyes (P = 0.0330, Wilcoxon
      signed rank test). The percentage increase in the b-wave amplitude correlated
      significantly with the percentage decrease in the mean parafoveal retinal
      thickness (r = 0.688, P = 0.0076). CONCLUSIONS: The decreased macular ERGs were
      partially recoverable in the early postoperative period. The decreased retinal
      edema after surgery may have contributed to this recovery.

PMID- 11980873
TI  - Regulation of retinal vascular endothelial growth factor and receptors in rabbits
      exposed to hyperoxia.
AB  - PURPOSE: To evaluate the molecular responses of vascular endothelial growth
      factor (VEGF) and its receptors to dexamethasone (Dex) and celecoxib (Cel) during
      hyperoxia and during hyperoxia followed by recovery in room air, in newborn
      rabbit retinas. METHODS: Newborn rabbits at 3 days postnatal age (n = 96)
      received room air or oxygen (80%-100%) for 4 days, during which they were
      administered saline (Sal), Dex, vehicle (Veh), or Cel (n = 12/treatment group).
      Six animals from each group were killed immediately after hyperoxia (or room air)
      and the remainder exposed to room air for 5 days. Retinal mRNA expression of
      VEGF(121), VEGF(165), VEGF receptor-1 (VEGFR-1, or Flt-1), and VEGFR-2 (or
      KDR/Flk-1) was determined. RESULTS: Hyperoxia resulted in increased retinal
      expression of mRNA of the VEGF splice variants in the groups treated with Sal,
      Dex, and Veh, whereas a decrease in VEGF(121) was noted in the Cel-treated group.
      In contrast, retinal Flt-1 receptor mRNA was markedly increased in the Cel
      treated group only, whereas retinal VEGFR-2 (KDR/Flk-1) receptor mRNA was
      suppressed in all the treatment groups. Hyperoxia followed by recovery in room
      air resulted in a minimal decrease in expression of retinal Flt-1 mRNA in the Sal
      and Dex groups. Cel treatment abolished its expression. CONCLUSIONS: The findings
      of increased retinal expression of VEGF mRNA in the newborn rabbit in response to
      hyperoxia are most likely due to species differences. Selective targeting of
      VEGF(121) and Flt-1 mRNA by Cel may represent one regulatory pathway for their
      anti-inflammatory effects. Further studies are needed to evaluate the therapeutic
      benefits of cyclooxygenase (COX)-2 inhibitors for the treatment and/or prevention
      of diseases associated with neovascularization.

PMID- 11980874
TI  - PGE(2)-mediated eNOS induction in prolonged hypercapnia.
AB  - PURPOSE: Because prostaglandins (PGs) are implicated in acute hypercapnia-induced
      hyperemia, this study was conducted to test the hypothesis that prolonged
      hypercapnia may cause a sustained increase in retinal blood flow (RBF) through a
      PG-dependent induction of endothelial nitric oxide synthase (eNOS). METHODS: Time
      dependent RBF (microsphere technique), PGE(2), nitrite (NO(2)(-)), and NOS
      protein (reduced nicotinamide adenine dinucleotide phosphate [NADPH]-diaphorase
      staining) production were measured in hypercapnia (6% CO(2))-treated piglets.
      From the same species, PGE(2), eNOS mRNA, NOS protein, and vasomotor responses
      were measured in eyecup preparations, as were Ca(2+) transients in
      neuroretinovascular endothelial cells. RESULTS: Hypercapnia caused biphasic (at
      0.5 hours and 6-8 hours) increases in RBF that were abolished with normalization
      of the pH. The early phase (0.5 hour) was associated with an increase in PGE(2)
      levels and the latter phase (6-8 hours) with an increase in NO(2)(-) and NOS
      protein. Inhibition of cyclooxygenase by diclofenac prevented the early and late
      increase in RBF. NOS inhibitor L-nitro-arginine prevented only the latter.
      Hypercapnic acidosis increased retinal PGE(2) levels and eNOS-dependent
      vasorelaxation ex vivo. The ex vivo time course of eNOS mRNA expression
      corresponded with the late-phase increase in RBF and was blocked by the
      transcription inhibitor actinomycin D and the receptor-operated Ca(2+) channel
      blocker SK&F96365. In neuroretinovascular cells, acidosis increased Ca(2+)
      transients, which were inhibited by SK&F96365, but not diclofenac. CONCLUSIONS:
      This study discloses a previously unexplored mechanism for late retinal hyperemia
      during sustained hypercapnia that appears secondary to the induced expression of
      eNOS mediated by PGE(2).

PMID- 11980875
TI  - Age as an independent risk factor for severity of experimental choroidal
      neovascularization.
AB  - PURPOSE: For many vascular diseases, aging appears to be an independent risk
      factor for severity of vascular complications, and blood vessels of aged
      individuals often demonstrate exaggerated repair responses to injury. This study
      was undertaken to determine the influence of aging on the severity of
      neovascularization in a mouse model of laser-induced choroidal neovascularization
      (CNV). METHODS: CNV was induced in young (2-month-old) and aged (16-month-old)
      C57BL/6 mice by making four separate choroidal burns in each eye with a diode red
      laser (650 nm). At 1, 2, and 4 weeks, the left eyes were removed for
      histopathology, and the right eyes were removed for flatmount analysis of CNV
      surface area, vascularity, and cellularity. RESULTS: Aged mice demonstrated a
      much larger area of CNV than did young mice (3.81 +/- 1.28 vs. 1.36 +/- 0.99 disc
      areas, P < 0.001) at 2 weeks, when the lesions showed maximum growth. Aged mice
      also demonstrated higher ratios for vascularity and cellularity of the CNV (1.34
      +/- 0.06 vs. 1.03 +/- 0.11, P < 0.0001 and 4.06 +/- 1.19 vs. 1.91 +/- 0.81, P <
      0.002 at 2 weeks, respectively). Histopathology revealed that CNV in older eyes
      was larger, thicker, and more cellular than in young eyes. CONCLUSIONS: In mice,
      age is associated with more severe CNV, defined as larger surface area, greater
      vascularity, and greater cellularity. Age-related systemic susceptibility
      factors, independent of local changes in the retina, may contribute to the
      greater severity of CNV in older than in younger individuals.

PMID- 11980876
TI  - Expression of pigment epithelium-derived factor in experimental choroidal
      neovascularization.
AB  - PURPOSE: To investigate the expression of pigment epithelium-derived factor
      (PEDF) in the rat laser-injury model of choroidal neovascularization (CNV).
      METHODS: Retinas were immunostained for PEDF at different times (1, 2, and 3
      weeks) after laser injury. Levels of PEDF protein in the vitreous at 1, 3, 7, 14,
      and 28 days after laser injury were also assayed by Western blot. RESULTS:
      Protein levels of PEDF in the vitreous were increased during the first 7 days
      after CNV induction. Immunostaining for PEDF was observed throughout normal
      nonlasered control retinas, sham-lasered retinas, and areas remote to laser
      lesions, which were generally more intense in the outer nuclear layer (ONL) and
      less intense in the internal nuclear layer (INL). Decreased expression of PEDF
      was observed in flanking areas adjacent to the injury site and was confined
      mainly to the ONL. In the injury sites, immunostaining within the ONL was either
      absent or decreased for up to 3 weeks after laser injury (the duration of the
      study). Preadsorption of the anti-PEDF antibody with the immunizing peptide
      blocked specific labeling in the retina. CONCLUSIONS: These results demonstrate
      an inverse correlation of expression of PEDF and formation of CNV in the
      experimental model and suggest that decreased expression of PEDF plays a
      permissive role in the formation of CNV. PEDF analogues may be a reasonable
      treatment strategy for CNV.

PMID- 11980877
TI  - A fundus camera dedicated to the screening of diabetic retinopathy in the primary
      care physician's office.
AB  - PURPOSE: To increase the number of diabetic patients being screened for
      retinopathy, an instrument, the DigiScope, was specifically designed to operate
      in primary-care physicians' offices. The DigiScope is described and its automated
      functions are evaluated. METHODS: The DigiScope consists of a semiautomated
      optical head to acquire fundus images, evaluate visual acuity, and transmit the
      data to a remote reading center through telephone lines. Normal volunteers and 17
      consecutive diabetic patients visiting their primary-care physician were
      recruited, and nonophthalmic staff performed the acquisition session. RESULTS:
      The pupil center and working distance were set automatically. Centering was
      achieved within 750 microm in less than 500 ms. The fundus was successfully
      focused by an automated algorithm, and an imaging session covering 71 degrees of
      the posterior pole of both eyes lasted 5.6 +/- 2.4 minutes. It was found that a
      file-compression ratio of 12 did not degrade the clinical information and allowed
      data transfer in less than 6 minutes. A pilot study in normal eyes showed that
      the DigiScope images yielded the same amount of details as conventional color
      fundus photographs obtained by an expert photographer. CONCLUSIONS: The DigiScope
      fulfills the instrumental requirements for a practical and cost-effective tool to
      acquire data needed to identify diabetic patients who must be referred to an eye
      care specialist. Widespread screening with the DigiScope may help reduce the risk
      of vision loss in an estimated 4 million individuals in the United States alone,
      who currently do not undergo an annual eye examination.

PMID- 11980878
TI  - Retinal thickness study with optical coherence tomography in patients with
      diabetes.
AB  - PURPOSE: To quantitatively assess retinal thickness by optical coherence
      tomography (OCT) in normal subjects and patients with diabetes. This study was
      intended to determine which retinal thickness value measured with OCT best
      discriminates between diabetic eyes, with and without macular edema. METHODS: OCT
      retinal thickness was measured by a manual technique in a total of 26 healthy
      volunteers (44 control eyes) and 85 patients with diabetes (148 eyes) with the
      clinical diagnosis of no diabetic retinopathy (45 eyes), nonproliferative
      diabetic retinopathy without clinically significant macular edema (CSME; 54
      eyes), proliferative diabetic retinopathy without CSME (21 eyes), and 28 eyes
      with diabetic retinopathy with CSME. Independent predictors of the presence of
      CSME were quantified by using univariate and multivariate logistic regression
      analyses. Receiver operating characteristic (ROC) curves were generated to
      evaluate and compare the predictor variables. The correlation of retinal
      thickness measurements and visual acuity was calculated. RESULTS: There were
      statistically significant differences in foveal thickness between control eyes
      and all the other eye groups (P = 0.001). Diabetic eyes with CSME had a
      statistically significant greater thickness in each of the areas compared with
      the other groups. In a multivariate logistic regression model, foveal thickness
      was a strong and independent predictor of CSME (odds ratio [OR], 1.037; 95%
      confidence interval [CI] 1.02-1.05). The area under the ROC curve of this
      predictor variable was 0.94 (P = 0.001). For a cutoff point of 180 microm, the
      sensitivity was 93%, and specificity was 75%. Foveal thickness correlated with
      visual acuity in a log minimum angle of resolution (logMAR) scale (Spearman's rho
      = 0.9, P = 0.001). CONCLUSIONS: These results suggest that foveal thickening over
      180 microm measured by OCT may be useful for the early detection of macular
      thickening and may be an indicator for a closer follow-up of the patient with
      diabetes.

PMID- 11980879
TI  - Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal
      outer plexiform layer.
AB  - PURPOSE: Mutations in the alpha(1F) subunit of voltage-dependent calcium channels
      (VDCCs) have been shown to cause incomplete congenital stationary night blindness
      (CSNB2). The purpose of this study was to dentify which of the four beta subunits
      of VDCCs participates in the formation of this channel at the photoreceptor
      synapse and to determine how its absence affects visual processing. METHODS: Mice
      without each of the four known beta subunits of VDCCs were generated by gene
      targeting and transgenic rescue (CNS-beta(1), -beta(2)) or by gene targeting
      alone (beta(3)) or were obtained from a commercial provider (beta(4)). Retinal
      function and visual sensitivity were examined by electroretinography and an
      active avoidance behavioral test, respectively. The structure of the retina and
      expression of the alpha(1F) subunit were examined at the light microscopic level
      and by immunohistochemistry. RESULTS: Under dark-adapted conditions, CNS-beta(2)
      null mice had a normal ERG a-wave, but did not have a normal b-wave. In addition,
      these mice showed decreased sensitivity to light. Both the a- and b-waves appear
      normal in the CNS-beta(1)-, beta(3)-, and beta(4)-null mice. Histologic analyses
      of all four mouse lines indicated that only the CNS-beta(2)-null mice had altered
      retinal morphology. Eyes of these mice had a thinner outer plexiform layer (OPL)
      than eyes of control animals. In addition, the labeling pattern of the alpha(1F)
      subunit in the OPL was altered in CNS-beta(2)-null mice. CONCLUSIONS: The normal
      distribution of the alpha(1F) subunit of the VDCCs in the OPL is dependent on the
      expression of the beta(2) subunit. The expression of both of these subunits is
      required for normal maintenance and/or formation of the OPL and synaptic
      transmission.

PMID- 11980880
TI  - Identification of the RPE65 protein in mammalian cone photoreceptors.
AB  - PURPOSE: The protein RPE65 plays a critical role in retinoid processing in the
      retinal pigment epithelium (RPE). Previous studies have identified the RPE65 mRNA
      in salamander cones, but not in rods. The purpose of the present study was to
      determine whether RPE65 is expressed at the protein level in mammalian cones, as
      well as in those of amphibians. METHODS: The specificity of the anti-RPE65
      antibody was demonstrated by Western blot analysis. RPE65 cellular localization
      was determined using immunohistochemistry on flatmounted retinas and retinal
      sections. RESULTS: RPE65 protein was detected in cones in flatmounted retinas of
      the mouse, rabbit, and cow, in addition to Xenopus laevis. The morphology and
      location of labeled cones in the retina were confirmed by double staining of
      mouse retina sections with the anti-RPE65 antibody and peanut agglutinin (PNA)
      lectin, which is known to label both types of cones in mouse. The double staining
      in the flatmounted retinas demonstrated that RPE65 was expressed in both types of
      the cones in the mouse retina. Under the same double-labeling conditions,
      however, cones in homozygous RPE65-knockout mouse were labeled by PNA lectin, but
      not by the anti-RPE65 antibody, indicating that the protein recognized by the
      anti-RPE65 antibody is encoded by the RPE65 gene rather than by another
      homologous gene. No RPE65 was detected in rods of any of the species tested.
      CONCLUSIONS: RPE65 is expressed in mammalian cones, but not in rods. These
      results provide further support for physiological observations that cones may
      have an alternative retinoid cycle.

PMID- 11980881
TI  - Intraocular adenoviral vector-mediated gene transfer in proliferative
      retinopathies.
AB  - PURPOSE: The purpose of this study was to compare levels and patterns of
      expression of reporter genes achieved with an E1-deleted and partially E3-deleted
      type 5 adenoviral (Ad) vector after intravitreous or subretinal injections, or
      after intravitreous injections in mouse eyes with proliferative retinopathies.
      METHODS: Ad vectors containing reporter gene constructs were injected into the
      vitreous cavity or subretinal space of wild-type mice or mice with proliferative
      retinopathies, and quantitative comparisons were made of expression of
      transgenes. RESULTS: In normal eyes, peak Ad-mediated expression of luciferase,
      driven by a cytomegalovirus (CMV) promoter, occurred after injection of 10(7) to
      10(8) viral particles and was 10 times greater after subretinal injections than
      after intravitreous injections. Intravitreous injections of Ad containing beta
      galactosidase (LacZ) expression constructs (AdLacZ.10) resulted in strong
      expression of LacZ in epithelial cells of the iris and ciliary body and focal
      expression in the retina. Subretinal injections of AdLacZ.10 resulted in strong
      expression in RPE cells. Expression of LacZ after intravitreous injection of
      AdLacZ.10 was significantly greater in mice with two types of proliferative
      retinopathy (ischemic retinopathy or transgenic mice with retina-specific
      expression of platelet-derived growth factor (PDGF)-BB or PDGF-AB) than
      littermate control animals. Cells within epiretinal membranes and activated
      Muller cells were preferentially transduced in eyes with proliferative
      retinopathy. CONCLUSIONS: These data suggest that although higher intraocular
      expression levels can be achieved after subretinal injection of adenoviral
      vectors, intravitreous injections provide good transduction of cells lining the
      vitreous cavity. Compared with normal eyes, eyes with proliferative retinopathy
      showed increased transduction, which occurred preferentially in cells
      participating in the disease process. Intravitreous injection of adenoviral
      vectors containing appropriate expression constructs may provide a good strategy
      for acute treatment of proliferative retinopathies, such as diabetic retinopathy
      and proliferative vitreoretinopathy.

PMID- 11980882
TI  - Spatiotemporal expression patterns of N-syndecan, a transmembrane heparan sulfate
      proteoglycan, in developing retina.
AB  - PURPOSE: N-syndecan is a transmembrane heparan sulfate proteoglycan, that is
      highly expressed in neural tissues. In the current study, changes in N-syndecan
      expression during retinal development were examined. METHODS: Localization of N
      syndecan in developing rat retina was examined by immunohistochemistry and in
      situ hybridization. The amount of the core protein was evaluated by immunoblot
      analysis, using retinal homogenates at various developmental stages. In addition,
      mRNA expression was semiquantified by reverse transcription-polymerase chain
      reaction (RT-PCR). To understand better the localization of N-syndecan in retinal
      neuronal cells, we performed immunocytochemistry using retinal ganglion cells in
      culture. RESULTS: N-syndecan is highly expressed in nerve fiber-rich layers of
      the retina at early postnatal stages (between postnatal day [P]0 and P14). In
      contrast, immunoreactivity was faint during embryonic stages and late postnatal
      stages. In addition, in retinal flatmounted sections, N-syndecan immunoreactivity
      was observed on the axons of retinal ganglion cells. Intense signals were
      observed in the ganglion cell layer during in situ hybridization. Immunoblot
      analyses demonstrated that the amount of N-syndecan core protein reached a peak
      at approximately P14. The RT-PCR analyses using N-syndecan primers showed that an
      intense amplified band was observed in the cDNA derived from P14 retinas, whereas
      only faint bands were detected in the embryonic day (E)16 and P42 retinas. In
      retinal ganglion cells in culture, N-syndecan was located on the long, extended
      neurites. CONCLUSIONS: The data show that N-syndecan is transiently expressed,
      primarily in retinal neural fibers, during retinal development, indicating that
      it may be involved in formation of the retinal neural network.

PMID- 11980883
TI  - In vitro differentiation capacity of telomerase immortalized human RPE cells.
AB  - PURPOSE: To investigate conditions promoting the differentiation of cultured
      human retinal pigment epithelial (RPE) cells and assess the differentiation
      potential of telomerase-immortalized RPE cells. METHODS: Serially passaged RPE
      340 (parental) cells have limited replicative ability and senesce after 50 to 60
      population doublings (PD)s. RPE 340 cells transfected with the catalytic
      component of human telomerase (hTERT) have an extended lifespan. RPE 340 and
      hTERT-transfected RPE (hTERT-RPE) cells were maintained at confluence without
      serum for up to 12 weeks. Morphologic, immunocytochemical, flow cytometric, and
      spectrophotometric analyses were performed to examine the extent of RPE
      differentiation. RESULTS: Parental RPE 340 and hTERT-RPE cells underwent growth
      arrest and differentiated in the absence of serum. In early-passage parental
      (PD11) and hTERT-RPE (PD115 and PD300) cells, serum deprivation for 4 weeks or
      more induced terminal differentiation as characterized by mature, growth
      arrested, confluent sheets of polygonal and melanized cells that demonstrated
      diminished 5'-bromo-2'-deoxyuridine (BrdU) uptake and positive reactivity with
      antibodies to cellular retinaldehyde-binding protein (CRALBP), cytokeratin, and
      vimentin. Reintroduction of serum at 4 or 8 weeks allowed the cells to reenter
      the cell cycle and demelanize. Midpassage (PD 25) parental cells, however, were
      irreversibly arrested at G(1) after 8 weeks of serum deprivation. CONCLUSIONS:
      Cultured parental and hTERT-RPE cells express RPE-associated proteins and become
      stably melanized when density is arrested in the absence of serum. Moreover,
      hTERT-immortalized RPE cells retain the capacity to undergo terminal
      differentiation in vitro, even after long-term culture.

PMID- 11980884
TI  - Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal
      ganglion cells by optic nerve transection.
AB  - PURPOSE: To examine the involvement of c-Jun and c-Jun N-terminal phosphorylation
      (JNP) in apoptosis of retinal ganglion cells (RGCs) after the optic nerve (ON)
      transection. METHODS: The expression and phosphorylation of c-Jun protein and
      apoptosis in RGCs were examined after ON transection in wild-type mice and mice
      in which both phosphoacceptor serines of Jun have mutated to alanines (c-Jun[AA]
      mice). The fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI) was applied to the superior
      colliculi (SC), and the right ON was severed after 7 days. After two more weeks,
      the average number of RGCs per field was calculated. RESULTS: JNP and TUNEL
      labeled apoptotic nuclei were detected in the ganglion cell layer (GCL) of the
      retina of the wild-type mice in response to ON transection. The numbers of TUNEL
      positive nuclei in the c-Jun(AA) mice was reduced in comparison to those in wild
      type mice. Retrograde labeling showed that the number of the RGCs in the retinas
      on the injured side of the c-Jun(AA) mice was significantly higher than in wild
      type mice 14 days after the lesion. CONCLUSIONS: These results suggest that there
      is a partial but significant contribution of JNP to the induction of apoptosis in
      RGCs by ON transection.

PMID- 11980885
TI  - Bax is not the heterodimerization partner necessary for sustained anti
      photoreceptor-cell-death activity of Bcl-2.
AB  - PURPOSE: Ectopic expression of Bcl-2 in photoreceptors of certain mouse models of
      retinitis pigmentosa (RP) temporarily slows disease progression. The temporary
      effect produced by Bcl-2 may result from insufficient levels of functional
      complexes between Bcl-2 and additional proteins necessary for maintaining the
      anti-apoptotic activity of Bcl-2. Although the overexpression of Bax generally
      induces apoptosis, Bax exerts anti-apoptotic properties when complexed with Bcl-2
      in certain cell culture systems. These studies were designed to determine whether
      coexpression of Bcl-2 and Bax would improve the neuroprotective effect provided
      by Bcl-2 alone in photoreceptors of mice with autosomal dominant RP (adRP).
      METHODS: Transgenic mice were produced that overexpressed Bax and Bcl-2
      specifically in photoreceptor cells, using the murine opsin promoter to drive
      transgene expression. These mice were crossed with an adRP mouse model to assess
      the effect of coexpression of Bax and Bcl-2 on retinal degeneration. Morphologic
      analysis was performed on retinas isolated at various developmental times to
      monitor disease progression. RESULTS: Ectopic expression of Bax in photoreceptors
      resulted in extensive rod cell death dependent on the level of Bax transgene
      expression. Although Bcl-2 was able to inhibit Bax-induced photoreceptor cell
      death, the coexpression of Bcl-2 and Bax in photoreceptors of mice with adRP did
      not enhance the protective effect against photoreceptor cell death exerted by Bcl
      2 alone. CONCLUSIONS: Coexpression of Bax and Bcl-2, at the levels produced in
      the transgenic lines, does not extend the temporary neuroprotective effect
      produced by Bcl-2 in photoreceptors of mice with adRP.

PMID- 11980886
TI  - Effects of protein kinase C on delayed rectifier K+ channel regulation by
      tyrosine kinase in rat retinal pigment epithelial cells.
AB  - PURPOSE: Investigation of the regulation of delayed rectifier potassium channels
      by protein kinases in retinal pigment epithelial (RPE) cells. METHODS: Membrane
      currents of cultured RPE cells were measured in either the perforated-patch or
      whole-cell configuration of the patch-clamp technique. RESULTS: Different
      potassium channel blockers from animal venoms (charybdotoxin, hanatoxin,
      agitoxin, tityustoxin) were used to identify the delayed rectifying outward
      current in RPE cells as current through potassium channels, mainly composed of
      Kv1.3 subunits. Extracellular application of a tyrosine kinase blocker, such as
      genistein (100 microM), lavendustin A (10 microM), or herbimycin A (4 microM),
      almost completely abolished the delayed rectifier currents. Intracellular
      application of the tyrosine kinase pp60(c-src) (30 U/mL) through a patch pipette
      led to an increase of the delayed rectifier current consistent with an activation
      of the delayed rectifier channels by src subtype tyrosine kinase. Inhibition
      (with 1 microM chelerythrine) or activation (with 1 microM phorbol ester PMA) of
      protein kinase C (PKC) did not change the activity of delayed rectifier channels.
      Inhibition of PKC also did not change the effect of tyrosine kinase inhibition of
      delayed rectifier currents. However, in cells with stimulated PKC, inhibition of
      tyrosine kinase by genistein led to an increase of delayed rectifier currents.
      Intracellular application of pp60(c-src) (30 U/mL) in cells with stimulated PKC
      led to inhibition of delayed rectifier currents. CONCLUSIONS. Tyrosine kinase, of
      the src family, can activate or inhibit delayed rectifier channels composed of
      Kv1.3 subunits in RPE cells. The activity of PKC determines whether tyrosine
      kinase activates or inhibits these K+ channels.

PMID- 11980887
TI  - Retinal cAMP levels during the progression of retinal degeneration in rhodopsin
      P23H and S334ter transgenic rats.
AB  - PURPOSE: To test whether high levels of cAMP promote apoptosis and shorten the
      life of retinal rod photoreceptors, the changes in cAMP levels during retinal
      degeneration were analyzed in two transgenic rat models that express rhodopsin
      P23H and S334ter mutations. METHODS: Dark- and light-adapted heterozygous P23H
      (lines 1 and 3; P23H-1 and -3), S334ter line 4 (S334ter-4), and Sprague-Dawley
      (control) rats were studied at 4 to 8 weeks by cAMP enzyme competitive
      immunoassay and by cAMP immunocytochemistry. RESULTS: In control animals retinal
      cAMP content reached a steady state level at 30 days of age. Dark-adapted control
      retinas had up to 97% higher cAMP content than light-adapted retinas, and
      photoreceptor cells were the major source of this increase. Dark-adapted
      photoreceptors in all three lines of transgenic rats at advanced stages of
      retinal degeneration had cAMP content different from that of the control. In rats
      that express mutant rhodopsin, the number of photoreceptor cells was
      progressively reduced, because of retinal degeneration, but dark-adapted cAMP
      levels did not decline accordingly. P23H transgenic animals of both lines had
      higher levels of cAMP per photoreceptor cell count than control animals. This
      elevation was more pronounced as degeneration progressed. S334ter animals showed
      smaller cAMP elevation than P23H rats at a similar stage of retinal degeneration,
      but at a point when S334ter rats were undergoing rapid retinal degeneration,
      whereas in P23H rats retinal degeneration was slowing down. CONCLUSIONS: All
      three lines of transgenic rats carrying rhodopsin mutations show an increase in
      dark-adapted photoreceptor cAMP levels. A complex relationship exists between
      cAMP levels and the rate of cell death in the retina. Although initially higher
      levels of cAMP may promote cell survival and slow down retinal degeneration,
      ultimately, elevated cAMP levels may become toxic and may contribute to retinal
      cell death.

PMID- 11980888
TI  - Visual pigment coexpression in Guinea pig cones: a microspectrophotometric study.
AB  - PURPOSE: To determine the visual pigment content of the rods and cones of the
      guinea pig (Cavia porcellus) and to quantify the level of coexpression of
      pigments within individual cones. METHODS: Microspectrophotometry was used to
      measure the absorbance spectrum of visual pigments in individual rods and cones
      from three retinal regions: dorsal, ventral, and a subequatorial transition zone.
      Partial bleaching was used to establish whether two spectrally distinct visual
      pigments were present within a single cone. RESULTS: Rods possessed a pigment
      with a wavelength of maximum absorbance (lambda(max)) close to 500 nm. A
      population of middle-wave-sensitive cones (M cones) contained a pigment with
      lambda(max) at approximately 530 nm, and a short-wave-sensitive cone population
      (S cones) contained a pigment with lambda(max) close to 400 nm. The majority of
      cones in all regions were M cones. Approximately 10% of cones in the transition
      region were found to coexpress the M and S cone pigments in a ratio of
      approximately 4:1. Coexpression was not detected in S cones. CONCLUSIONS: In C.
      porcellus, coexpression of cone pigments occurs in a small number of cells but is
      biased in favor of the M pigment. Given the relatively low level of coexpression,
      detectable in only approximately 10% of the cones in the transition region, it is
      unlikely to cause any significant detriment to dichromatic color vision.

PMID- 11980889
TI  - A new wavelet in the multifocal electroretinogram, probably originating from
      ganglion cells.
AB  - PURPOSE: To report the properties of a newly detected positive wavelet on the
      descending limb of P1 of the first-order kernel of the human multifocal
      electroretinogram (mfERG). METHODS: Twenty eyes of 20 normal individuals, ages 21
      to 29 years (mean, 25.6) and nine eyes of 6 patients with optic neuritis ages 5
      to 38 years (mean, 17.3) were studied. mfERGs were recorded with a visual evoked
      response imaging system with the number of stimulus elements set at 37. The
      stimulus frequency was changed from 75 to 37, 18, 9.4, 4.7, and 2.3 Hz, and the
      contrast of the stimuli was lowered to 50%. RESULTS: In normal eyes, a positive
      wavelet appeared on the descending limb of P1 of the first-order kernel of the
      mfERG when the stimulus frequency was reduced from 75 to 18 Hz. The wavelet had a
      mean amplitude of 4.2 nV/deg(2) and a mean implicit time of 34 ms at 18 Hz. When
      the stimulus frequency was reduced further to 2.3 Hz, the amplitude of the
      wavelet increased significantly (P < 0.05) compared with that at 18 Hz. The
      amplitudes of the wavelet elicited from the nasal side of the retina were
      significantly larger (P < 0.05) than those from the temporal side and decreased
      significantly (P < 0.05) with increasing distance from the optic disc. The
      wavelet was not present in any of the patients with newly diagnosed optic
      neuritis, but reappeared with recovery from the disease. The recovery of the
      wavelet correlated significantly with the recovery of visual acuity and of
      central critical fusion frequency. CONCLUSIONS: The amplitude of the wavelet on
      the descending limb of P1 of the first-order kernel of the mfERG was dependent on
      the stimulus frequency and the retinal locus. The wavelet was not present in the
      mfERGs recorded in patients with optic neuritis, but returned with recovery from
      the disease. These findings suggest that the neural activity of the ganglion
      cells give rise to this wavelet.

PMID- 11980890
TI  - Retinal origins of the primate multifocal ERG: implications for the human
      response.
AB  - PURPOSE: To better understand the cellular contributions to the human multifocal
      ERG (mfERG), rhesus monkey and human mfERGs were recorded using the same stimulus
      conditions. The monkey mfERGs were recorded before and after injections of
      pharmacologic agents known to selectively block activity of particular cells and
      circuits in the retina. METHODS: Photopic mfERGs were recorded with Dawson-Trick
      Litzkow (DTL) fiber electrodes from 16 eyes of 10 anesthetized adult rhesus
      monkeys (Macaca mulatta) and from 4 normal humans. The display consisted of 103
      equal-sized hexagons within 17 degrees of the fovea. Monkey mfERGs were obtained
      before and after inner retinal responses were suppressed with intravitreal
      injections of tetrodotoxin (TTX), TTX+N-methyl-D-aspartic acid (NMDA), TTX+NMDA
      with the gamma-aminobutyric acid (GABA(A&C)) antagonist picrotoxin (PTX), or the
      inhibitory amino acid GABA and after L-2 amino-4-phosphonobutyric acid (APB) to
      block signal transmission to ON-bipolar cells. Finally, a combination of APB and
      cis-2,3 piperidine dicarboxylic acid (PDA) was used to isolate the contributions
      from the cone photoreceptors. RESULTS: TTX, which blocks sodium-based action
      potentials, removes a large contribution from the monkey's mfERG, but it does not
      remove all inner retinal influences. After administration of TTX, the mfERG is
      further modified by the addition of NMDA. TTX+NMDA, TTX+NMDA+PTX, or GABA alone
      have similar effects, suggesting that, at the concentrations used, they are
      largely removing the inner retinal contributions. After removing the inner
      retinal influences, the monkey's mfERG is mainly composed of ON- and OFF-bipolar
      contributions, as revealed after APB and PDA were injected. The leading edge of
      the first negative potential (N1) is largely shaped by the initial
      hyperpolarization of the OFF-bipolar cells. The photoreceptors also contribute to
      the leading edge of N1, but this contribution is small, except in the central 6
      degrees. The depolarization of the ON-bipolars and the recovery of the OFF
      bipolars contribute to the leading edge of the major positive component (P1),
      with the recovery of the ON-bipolars being the dominant influence on the trailing
      edge. The waveform of the human mfERG most closely resembles the rhesus monkey's
      mfERG after administration of TTX. CONCLUSIONS: The monkey's mfERG is shaped by
      large contributions from ON- and OFF-bipolar cells, combined with both spiking
      and nonspiking inner retinal contributions, and a small contribution from the
      photoreceptors. In comparison, the human mfERG resembles the monkey's mfERG after
      reduction of inner retinal contributions. Based on the pharmacologic dissection
      of the monkey's mfERG, a model of the waveform of the human mfERG is proposed.
      This model suggests that the waveform can be understood as a combination of
      overlapping ON- and OFF-bipolar cell contributions combined with smaller
      contributions from inner retina and photoreceptors.

PMID- 11980891
TI  - Mechanisms of myopia in Cohen syndrome mapped to chromosome 8q22.
AB  - PURPOSE: To analyze the mechanisms of myopia in Cohen syndrome (Mendelian
      Inheritance in Man [MIM] no. 216550). METHODS: A cross-sectional study of 22
      Finnish patients (age range, 2-57 years) with Cohen syndrome, which maps to
      chromosome 8q22, was undertaken to record cycloplegic refraction, keratometry
      (corneal power and radius of curvature), biometry (anterior chamber depth [ACD],
      lens thickness [LT], axial [AL] and vitreal length [VL]), and Hoffer Q-modeled
      lens power. These components of refraction were correlated to age and spherical
      equivalent (SE) at the corneal plane. Contribution to total myopia of refractive
      (corneal and lenticular) and axial components was modeled by multiple linear
      regression and by estimating the effect of deviation from population mean values.
      RESULTS: The mean SE in patients with Cohen syndrome older than 10 years was 
      9.35 D; the mean cylinder power, +1.70 D; and the mean anisometropia, 0.53 D.
      Relative to the emmetropic eye of a young adult, the AL and VL (mean, 23.9 and
      16.6 mm, respectively) and lens power (mean, 30.30 D) were higher in 74% and 93%
      of patients, respectively, and the ACD (mean, 2.5 mm) was smaller and the LT
      (mean, 4.9 mm) and corneal power (mean, 45.63 D) higher than average in all
      patients. Corneal power (r = 0.513, P = 0.021) increased with age, but AL and VL
      (P = 0.46 and 0.54, respectively) and lens power (P = 0.89) did not correlate
      with age. The lens power decreased with AL (r = -0.564, P = 0.029) and tended to
      increase with corneal power (r = 0.475, P = 0.074). Multiple linear regression
      identified AL and corneal power as independent predictors of SE. Based on
      deviation from population means, the lens power explained 55%, corneal power 23%,
      and AL 22% of total myopia. ACD decreased and LT increased markedly with age,
      rendering angle-closure glaucoma a possibility. CONCLUSIONS: Myopia in Cohen
      syndrome is mainly refractive in type and is due to high corneal and lenticular
      power, which is otherwise rare in young patients. It may be superimposed on axial
      myopia, probably related to polygenic factors that determine myopia in the
      general population. The refractive myopia in Cohen syndrome may result from
      dysgenesis and atrophy of the cornea, ciliary body, and iris, which in turn cause
      iridial and zonular laxity and spherophakia.

PMID- 11980892
TI  - Molecular cloning of CoA Synthase. The missing link in CoA biosynthesis.
AB  - Coenzyme A functions as a carrier of acetyl and acyl groups in living cells and
      is essential for numerous biosynthetic, energy-yielding, and degradative
      metabolic pathways. There are five enzymatic steps in CoA biosynthesis. To date,
      molecular cloning of enzymes involved in the CoA biosynthetic pathway in mammals
      has been only reported for pantothenate kinase. In this study, we present cDNA
      cloning and functional characterization of CoA synthase. It has an open reading
      frame of 563 aa and encodes a protein of approximately 60 kDa. Sequence
      alignments suggested that the protein possesses both phosphopantetheine
      adenylyltransferase and dephospho-CoA kinase domains. Biochemical assays using
      wild type recombinant protein confirmed the gene product indeed contained both
      these enzymatic activities. The presence of intrinsic phosphopantetheine
      adenylyltransferase activity was further confirmed by site-directed mutagenesis.
      Therefore, this study describes the first cloning and characterization of a
      mammalian CoA synthase and confirms this is a bifunctional enzyme containing the
      last two components of CoA biosynthesis.

PMID- 11980893
TI  - Two-state conformational changes in inositol 1,4,5-trisphosphate receptor
      regulated by calcium.
AB  - Inositol 1,4,5-trisphosphate receptor (IP3R) is a highly controlled calcium
      (Ca2+) channel gated by inositol 1,4,5-trisphosphate (IP3). Multiple regulators
      modulate IP3-triggered pore opening by binding to discrete allosteric sites
      within IP3R. Accordingly we have postulated that these regulators structurally
      control ligand gating behavior; however, no structural evidence has been
      available. Here we show that Ca2+, the most pivotal regulator, induced marked
      structural changes in the tetrameric IP3R purified from mouse cerebella. Electron
      microscopy of the IP3R particles revealed two distinct structures with 4-fold
      symmetry: a windmill structure and a square structure. Ca2+ reversibly promoted a
      transition from the square to the windmill with relocations of four peripheral
      IP3-binding domains, assigned by binding to heparin-gold. Ca2+-dependent
      susceptibilities to limited digestion strongly support the notion that these
      alterations exist. Thus, Ca2+ appeared to regulate IP3 gating activity through
      the rearrangement of functional domains.

PMID- 11980894
TI  - Activation of caspase pathways during iron chelator-mediated apoptosis.
AB  - Iron chelators have traditionally been used in the treatment of iron overload.
      Recently, chelators have also been explored for their ability to limit oxidant
      damage in cardiovascular, neurologic, and inflammatory disease as well as to
      serve as anti-cancer agents. To determine the mechanism of cell death induced by
      iron chelators, we assessed the time course and pathways of caspase activation
      during apoptosis induced by iron chelators. We report that the chelator
      tachpyridine sequentially activates caspases 9, 3, and 8. These caspases were
      also activated by the structurally unrelated chelators dipyridyl and
      desferrioxamine. The critical role of caspase activation in cell death was
      supported by microinjection experiments demonstrating that p35, a broad spectrum
      caspase inhibitor, protected HeLa cells from chelator-induced cell death.
      Apoptosis mediated by tachpyridine was not prevented by blocking the CD95 death
      receptor pathway with a Fas-associated death domain protein (FADD) dominant
      negative mutant. In contrast, chelator-mediated cell death was blocked in cells
      microinjected with Bcl-XL and completely inhibited in cells microinjected with a
      dominant-negative caspase 9 expression vector. Caspase activation was not
      observed in cells treated with N-methyl tachpyridine, an N-alkylated derivative
      of tachpyridine which lacks an ability to react with iron. These results suggest
      that activation of a mitochondrial caspase pathway is an important mechanism by
      which iron chelators induce cell death.

PMID- 11980895
TI  - Distinct intracellular signaling in tumor necrosis factor-related apoptosis
      inducing ligand- and CD95 ligand-mediated apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent
      inducer of apoptosis in tumor cells but not in healthy cells. Similar to CD95
      ligand (CD95L), TRAIL signaling requires ligand-receptor interaction; the
      downstream signaling molecules, such as Fas-associated death domain and caspase
      8, also seem similar. Using cells stably expressing TRAIL and CD95L, we show that
      both TRAIL and CD95L induce apoptosis in the rat colon carcinoma cell line CC531.
      The mitochondrial damage (loss of mitochondrial membrane potential (MMP) and
      release of cytochrome c) observed after co-incubation with TRAIL-expressing cells
      occurs much earlier than that observed with CD95L-expressing cells. The decrease
      in MMP induced by both ligands was caspase-8-mediated; no difference in caspase-8
      activation by TRAIL and CD95L was found. TRAIL, but not CD95L, induced activation
      of caspase-10. bcl-2 overexpression could not prevent TRAIL-induced mitochondrial
      dysfunction, whereas it completely prevented CD95L-mediated loss of MMP and
      cytochrome c release. The selective effect of TRAIL on tumor cells and the
      apparent inability of bcl-2 to block TRAIL-induced apoptosis suggest that TRAIL
      may offer a lead for cancer therapy in the future.

PMID- 11980896
TI  - Structural basis for interactions between lung surfactant protein C and bacterial
      lipopolysaccharide.
AB  - In the respiratory tract, recognition of bacterial endotoxin (lipopolysacharide,
      LPS) is a critical step of the innate host defense system directed against
      invading pathogens. Secretions of the airways contain proteins that have direct
      antimicrobial activity (lysozyme, lactoferrin, defensins, and cathelicidins) as
      well as complement factors and surfactant proteins that contribute to host
      defense. The hydrophobic surfactant protein C (SP-C) recognizes LPS (Augusto, L.,
      Le Blay, K., Auger, G., Blanot, D., and Chaby, R. (2001) Am. J. Physiol. 281,
      L776-L785). In the present study, using synthetic analogs of SP-C, we demonstrate
      that the palmitoyl residues of SP-C are not required for the interaction with LPS
      and that both the hydrophilic and hydrophobic regions of SP-C are required for
      specific binding of a radiolabeled rough-type LPS. In addition, using LPS
      submitted to different chemical treatments as well as synthetic analogs of the
      lipid A moiety of LPS, we established that the terminal phosphate group at the
      reducing end of the lipid A disaccharide in alpha configuration is of crucial
      importance for recognition by SP-C. The N-linked fatty acyl chain on the reducing
      glucosamine of lipid A also takes part in the interaction. Dipalmitoyl
      phosphatidylcholine is not specifically required for the LPS-binding activity of
      SP-C, although a lipid environment significantly increases the binding. These
      results provide a basis for experiments on the role of SP-C in presentation of
      LPS to alveolar cells and for the design of drugs for the management of endotoxin
      induced lung injury.

PMID- 11980897
TI  - Molecular cloning and expression of a sixth type of alpha 2,8-sialyltransferase
      (ST8Sia VI) that sialylates O-glycans.
AB  - A novel member of the mouse alpha2,8-sialyltransferase (ST8Sia) family,
      designated ST8Sia VI, was identified by BLAST analysis of expressed sequence
      tags. The sequence of ST8Sia VI encodes a protein of 398 amino acids and shows
      42.0 and 38.3% amino acid sequence identities to mouse alpha2,8
      sialyltransferases ST8Sia I (GD3 synthase) and ST8Sia V (GD1c, GT1a, GQ1b, and
      GT3 synthases), respectively. The recombinant soluble form of ST8Sia VI expressed
      in COS-7 cells exhibited alpha2,8-sialyltransferase activity toward both
      glycolipids and glycoproteins that have the NeuAcalpha2,3(6)Gal sequence at the
      nonreducing end of their carbohydrate groups. This enzyme formed
      NeuAcalpha2,8NeuAc structures, but not oligosialic or polysialic acid structures.
      Analysis of the fetuin sialylated by ST8Sia VI indicated that ST8Sia VI prefers O
      glycans to N-glycans as acceptor substrates. Substrate specificities and kinetic
      properties also showed that ST8Sia VI prefers O-glycans to glycolipids as
      acceptor substrates. ST8Sia VI also exhibited activity toward oligosaccharides
      such as sialyllactose and sialyllactosamine, and the structure of the minimal
      acceptor substrate for ST8Sia VI was determined as the NeuAcalpha2,3(6)Gal
      sequence. The expression of the ST8Sia VI gene was ubiquitous, and the highest
      expression was observed in kidney, with three major transcripts of 8.2, 3.8, and
      2.7 kb. This is the first report of a mammalian alpha2,8-sialyltransferase that
      sialylates O-glycans preferentially.

PMID- 11980898
TI  - Differential regulation of vascular endothelial growth factor expression by
      peroxisome proliferator-activated receptors in bladder cancer cells.
AB  - The growth of any solid tumor depends on angiogenesis. Vascular endothelial
      growth factor (VEGF) plays a prominent role in vesical tumor angiogenesis
      regulation. Previous studies have shown that the peroxisome proliferator
      activated receptor gamma (PPARgamma) was involved in the angiogenesis process.
      Here, we report for the first time that in two different human bladder cancer
      cell lines, RT4 (derived from grade I tumor) and T24 (derived from grade III
      tumor), VEGF (mRNA and protein) is differentially up-regulated by the three PPAR
      isotypes. Its expression is increased by PPARalpha, beta, and gamma in RT4 cells
      and only by PPARbeta in T24 cells via a transcriptional activation of the VEGF
      promoter through an indirect mechanism. This effect is potentiated by an RXR
      (retinoid-X-receptor), selective retinoid LG10068 providing support for a PPAR
      agonist-specific action on VEGF expression. While investigating the downstream
      signaling pathways involved in PPAR agonist-mediated up-regulation of VEGF, we
      found that only the MEK inhibitor PD98059 reduced PPAR ligand-induced expression
      of VEGF. These data contribute to a better understanding of the mechanisms by
      which PPARs regulate VEGF expression. They may lead to a new therapeutic approach
      to human bladder cancer in which excessive angiogenesis is a negative prognostic
      factor.

PMID- 11980899
TI  - 2'-5' Oligoadenylate synthetase plays a critical role in interferon-gamma
      inhibition of respiratory syncytial virus infection of human epithelial cells.
AB  - Respiratory syncytial virus (RSV), associated with bronchiolitis and asthma, is
      resistant to the antiviral effects of type-I interferons (IFN), but not IFN
      gamma. However, the antiviral mechanism of IFN-gamma action against RSV infection
      is unknown. The molecular mechanism of IFN-gamma-induced antiviral activity was
      examined in this study using human epithelial cell lines HEp-2 and A549. Exposure
      of these cells to 100-1000 units/ml of IFN-gamma, either before or after RSV
      infection, results in a significant decrease in RSV infection. After 1 h of
      exposure, IFN-gamma induces protein expression of IFN regulatory factor-1 (IRF-1)
      but not IRF-2, double-stranded RNA-activated protein kinase, and inducible nitric
      oxide synthase in these cells. The mRNA for IRF-1, p40, and p69 isoforms of 2'-5'
      oligoadenylate synthetase (2-5 AS) are detectable, respectively, at 1 and 4 h of
      IFN-gamma exposure. Studies using cycloheximide and antisense oligonucleotides to
      IRF-1 indicate a direct role of IRF-1 in activating 2-5 AS. Cells transfected
      with 2-5 AS antisense oligonucleotides inhibit the antiviral effect of IFN-gamma.
      A stable cell line of HEp-2 overexpressing RNase L inhibitor, RLI-14, which
      exhibits an IFN-gamma-induced gene expression pattern similar to that of the
      parent cell line, shows a significant reduction in RNase L activity and IFN-gamma
      mediated antiviral effect, compared with HEp-2 cells. These results provide
      direct evidence of the involvement of 2-5 AS in IFN-gamma-mediated antiviral
      activity in these cells.

PMID- 11980900
TI  - The carboxyltransferase activity of the apicoplast acetyl-CoA carboxylase of
      Toxoplasma gondii is the target of aryloxyphenoxypropionate inhibitors.
AB  - Inhibition of growth of the apicomplexan parasite Toxoplasma gondii by
      aryloxyphenoxypropionate herbicides has been correlated with the inhibition of
      its acetyl-CoA carboxylase (ACC) by these compounds. Here, full-length and C
      terminal fragments of T. gondii apicoplast ACC as well as C-terminal fragments of
      the cytosolic ACC were expressed in Escherichia coli. The recombinant proteins
      that were soluble showed the expected enzymatic activities. Yeast gene
      replacement strains depending for growth on the expressed T. gondii ACC were
      derived by complementation of a yeast ACC1 null mutation. In vitro and in vivo
      tests with aryloxyphenoxypropionates showed that the carboxyltransferase domain
      of the apicoplast T. gondii ACC is the target for this class of inhibitors. The
      cytosolic T. gondii ACC is resistant to aryloxyphenoxypropionates. Both T. gondii
      isozymes are resistant to cyclohexanediones, another class of inhibitors
      targeting the ACC of grass plastids.

PMID- 11980901
TI  - Studies with chimeric Mpl/JAK2 receptors indicate that both JAK2 and the membrane
      proximal domain of Mpl are required for cellular proliferation.
AB  - The thrombopoietin (TPO) receptor c-Mpl, like other members of the cytokine
      receptor superfamily, requires the association and activation of Janus kinases
      (JAKs) for normal signal transduction. The membrane-proximal portion of the
      signaling domain, containing conserved box1 and box2 motifs, is sufficient to
      support the proliferation of cytokine-dependent cell lines and basal
      megakaryocytopoiesis in vivo. We hypothesized that activation of the JAK2 kinase
      alone might be sufficient for proliferative signaling. To test this premise, we
      constructed chimeric receptors in which the extracellular and transmembrane
      portions of Mpl were fused to the pseudokinase and kinase domains of murine JAK2
      kinase. When expressed in the interleukin-3-dependent cell line Ba/F3, the
      chimeric receptors were appropriately expressed on the cell surface and were able
      to initiate tyrosine kinase activity upon exposure to TPO. However, chimeric
      receptors lacking an intact box2 domain of Mpl were unable to support
      proliferation at any concentration of TPO. Only chimeric receptors containing
      both JAK2 kinase activity and the box2 region initiated proliferative signaling.
      Within the box2 motif, we determined that the sequence Glu(56)-Ile(57)-Leu(58) of
      the Mpl cytoplasmic domain is critical for proliferation of the chimeric
      receptors. Furthermore, TPO-dependent induction of c-myc transcription is also
      dependent on this motif. These results indicate that JAK2 activation alone is not
      sufficient for TPO-induced proliferation and that one or more essential signaling
      pathways must arise from the cytoplasmic domain of Mpl that includes box2.
      Although the nature of the signal transduction pathway is not yet known, this
      second proliferative event is likely to regulate c-myc expression.

PMID- 11980902
TI  - Evidence for cooperativity between the four binding sites of dimeric ArsD, an
      As(III)-responsive transcriptional regulator.
AB  - ArsD is a trans-acting repressor of the arsRDABC operon that confers resistance
      to arsenicals and antimonials in Escherichia coli. It possesses two-pairs of
      vicinal cysteine residues, Cys(12)-Cys(13) and Cys(112)-Cys(113), that
      potentially form separate binding sites for the metalloids that trigger
      dissociation of ArsD from the operon. However, as a homodimer it has four vicinal
      cysteine pairs. Titration of the steady-state fluorescence of ArsD with
      metalloids revealed positive cooperativity, with a Hill coefficient of 2, between
      these sites. Disruption of the Cys(112)-Cys(113) site by mutagenesis of arsD, but
      not the Cys(12)-Cys(13) site, largely abolished this cooperativity, indicative of
      interactions between adjacent Cys(112)-Cys(113) sites within the dimer. The
      kinetics of metalloid binding were determined by stopped flow spectroscopy; the
      rate increased in a sigmoidal manner, with a Hill coefficient of 4, indicating
      that the pre-steady-state measurements reported cooperativity between all four
      sites of the dimer rather than just the intermolecular interactions reported by
      the steady-state measurements. The kinetics of Sb(III) displacement by As(III)
      revealed that the metalloid-binding sites behave differentially, with the rapid
      exchange of As(III) for Sb(III) at one site retarding the release of Sb(III) from
      the other sites. We propose a model involving the sequential binding and release
      of metalloids by the four binding sites of dimeric ArsD, with only one site
      releasing free metalloids.

PMID- 11980903
TI  - Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses
      in eosinophils and basophils.
AB  - We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on
      eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a
      potent and selective inducer of eosinophil and basophil shape change. In
      eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory
      burst, and L-selectin shedding but did not cause up-regulation of CD63
      expression. Pretreatment of eosinophils with indomethacin also enhanced
      subsequent eosinophil shape change induced by eotaxin, although treatment with
      higher concentrations of indomethacin resulted in a decrease in the expression of
      the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell
      selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil
      shape change in response to eotaxin was inhibited by pertussis toxin, but
      indomethacin- and PGD(2)-induced shape change responses were not. Treatment of
      eosinophils with specific inhibitors of phospholipase C (U-73122),
      phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein
      kinase (SB-202190) revealed roles for these pathways in indomethacin signaling.
      Indomethacin and its analogues may therefore provide a structural basis from
      which selective PGD(2) receptor small molecule antagonists may be designed and
      which may have utility in the treatment of allergic inflammatory disease.

PMID- 11980904
TI  - Calcium/calmodulin-dependent protein kinase II phosphorylates and regulates the
      Drosophila eag potassium channel.
AB  - Modulation of neuronal excitability is believed to be an important mechanism of
      plasticity in the nervous system. Calcium/calmodulin-dependent protein kinase II
      (CaMKII) has been postulated to regulate the ether a go-go (eag) potassium
      channel in Drosophila. Inhibition of CaMKII and mutation of the eag gene both
      cause hyperexcitability at the larval neuromuscular junction (NMJ) and memory
      formation defects in the adult. In this study, we identify a single site,
      threonine 787, as the major CaMKII phosphorylation site in Eag. This site can be
      phosphorylated by CaMKII both in a heterologous cell system and in vivo at the
      larval NMJ. Expression of Eag in Xenopus oocytes was used to assess the function
      of phosphorylation. Injection of either a specific CaMKII inhibitor peptide or
      lavendustin C, another CaMKII inhibitor, reduced Eag current amplitude acutely.
      Mutation of threonine 787 to alanine also reduced amplitude. Moreover, both
      CaMKII inhibition and the alanine mutation accelerated inactivation. The
      reduction in current amplitudes and the accelerated inactivation of
      dephosphorylated Eag channels would result in decreased outward potassium
      currents and hyperexcitability at presynaptic terminals and, thus, are consistent
      with the NMJ phenotype observed when CaMKII is inhibited. These results show that
      Eag is a substrate of CaMKII and suggest that direct modulation of potassium
      channels may be an important function of this kinase.

PMID- 11980905
TI  - Regulation of CCAAT/enhancer-binding protein (C/EBP) activator proteins by
      heterodimerization with C/EBPgamma (Ig/EBP).
AB  - The CCAAT/enhancer-binding proteins (C/EBPs) are basic leucine zipper
      transcription factors that play important roles in regulating cell growth and
      differentiation. C/EBP proteins form leucine zipper-mediated homodimers but are
      also capable of heterodimerizing with other C/EBPs in vitro. Here we show that
      C/EBPbeta occurs predominantly as a heterodimer that displays rapid mobility in
      gel shift assays. Biochemical fractionation and antibody supershift assays
      demonstrate that the C/EBPbeta heterodimeric partner is C/EBPgamma (Ig/EBP), a
      C/EBP protein that has been implicated as an inhibitor of other family members.
      Although most cell types express C/EBPbeta.C/EBPgamma heterodimers, macrophages
      contain a C/EBPbeta partner that is serologically distinct from C/EBPgamma. We
      found that C/EBPgamma blocked the ability of C/EBPbeta and C/EBPgamma to activate
      a reporter gene in L cell fibroblasts but did not inhibit a chimeric C/EBPbeta
      protein containing the GCN4 leucine zipper. Repression by C/EBPgamma occurs at
      the level of transactivation and requires heterodimerization with the C/EBP
      partner. C/EBPgamma was an ineffective repressor in HepG2 hepatoma cells despite
      forming C/EBP heterodimers, and C/EBPalpha was not effectively inhibited in
      either L or HepG2 cells. Our findings demonstrate that C/EBPgamma modulates C/EBP
      activity in a cell- and isoform-specific manner.

PMID- 11980906
TI  - Cyclin L is an RS domain protein involved in pre-mRNA splicing.
AB  - We report the cDNA cloning and functional characterization of human cyclin L, a
      novel cyclin related to the C-type cyclins that are involved in regulation of RNA
      polymerase II (pol II) transcription. Cyclin L also contains a COOH-terminal
      dipeptide repeat of alternating arginines and serines, a hallmark of the SR
      family of splicing factors. We show that recombinant cyclin L interacts with p110
      PITSLRE kinase, and that cyclin L antibody co-immunoprecipitates a kinase
      activity from HeLa nuclear extracts that phosphorylates the carboxyl-terminal
      domain (CTD) of pol II and splicing factor SC35, and is inhibited by the cdk
      inhibitor p21. Cyclin L antibody inhibits the second step of RNA splicing in
      vitro, and recombinant cyclin L protein stimulates splicing under suboptimal
      conditions. Significantly, the IC(50) for splicing inhibition by p21 is similar
      to the IC(50) for inhibition of the cyclin L-associated kinase activity. Cyclin L
      and its associated kinase are thus new members of the pre-mRNA processing
      machinery.

PMID- 11980907
TI  - AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein,
      induces caspase-independent apoptosis.
AB  - Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that triggers
      caspase-independent apoptosis. We describe here the cloning and characterization
      of a novel AIF-homologous molecule designated AMID (AIF-homologous mitochondrion
      associated inducer of death). AMID lacks a mitochondrial localization sequence
      but shares significant homology with AIF and NADH oxidoreductases from bacteria
      to mammalian species. Immunofluorescent staining and biochemical experiments
      indicated that AMID was co-localized with mitochondria. Overexpression of AMID
      induced cell death with characteristic apoptotic morphology. Furthermore, AMID
      induced apoptosis was independent of caspase activation and p53 and was not
      inhibited by Bcl-2. These findings suggest that AMID induces a novel caspase
      independent apoptotic pathway.

PMID- 11980908
TI  - A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va
      function in melanosome transport.
AB  - The Rab27a GTPase regulates diverse processes involving lysosome-related
      organelles, including melanosome motility in melanocytes, and lytic granule
      release in cytotoxic T lymphocytes. Toward an understanding of Rab27a function,
      we searched for proteins that interact with Rab27a(GTP) using the yeast two
      hybrid system and identified JFC1/Slp1, a protein of unknown function. JFC1/Slp1
      and related proteins, including melanophilin, contain a conserved amino-terminal
      domain similar to the Rab3a-binding domain of Rabphilin-3. We used several
      methods to demonstrate that this conserved amino-terminal domain is a Rab27
      binding domain. We show that this domain interacts directly, and in a GTP
      dependent manner with Rab27a. Furthermore, overexpression of this domain in
      melanocytes results in perinuclear clustering of melanosomes, suggesting that
      this region is sufficient for interaction with, and perturbation of function of,
      Rab27a in a physiological context. Thus, we identified a novel family of Rab27
      binding proteins. We also show that melanophilin associates with Rab27a and
      myosin Va on melanosomes in melanocytes, and present evidence that a domain
      within the carboxyl-terminal region of melanophilin interacts with the carboxyl
      terminal tail of the melanocyte-specific splice isoform of myosin Va. Thus,
      melanophilin can associate simultaneously with activated Rab27a and myosin Va via
      distinct regions, and serve as a linker between these proteins.

PMID- 11980909
TI  - E2F-3B is a physiological target of cyclin A.
AB  - The E2F family of transcription factors controls the expression of numerous genes
      that are required for the G(1)/S transition. Among the mechanisms that modulate
      the activity of the E2F proteins, cyclin A has been found to be important for the
      down-regulation of E2F-1, -2, and -3A activity after cells have progressed
      through G(1)/S. Specifically, phosphorylation of these E2F proteins by cyclin
      A/Cdk2 ultimately results in their necessary degradation as cells progress
      through S phase. E2F-3B was recently identified as an alternatively spliced form
      of E2F-3A that was predicted to lack a functional cyclin A binding domain. In
      this paper, we present considerable evidence that contradicts this prediction.
      First, we demonstrate binding of cyclin A to E2F-3B as bacterially expressed
      proteins in vitro. Second, we demonstrate binding of cyclin A to E2F-3B in
      mammalian cells in vivo. Third, we show that co-expression of cyclin A with E2F
      3B significantly reduces E2F-3B-mediated transcriptional activity. Finally, in
      synchronized cells, we observe down-regulation of E2F-3B protein expression
      coincident with the up-regulation of cyclin A. We conclude that E2F-3B is a
      physiological target of cyclin A.

PMID- 11980910
TI  - Mirk protein kinase is activated by MKK3 and functions as a transcriptional
      activator of HNF1alpha.
AB  - Mirk/Dyrk1B is an arginine-directed serine/threonine protein kinase that is
      expressed at low levels in most normal tissues but at elevated levels in many
      tumor cell lines and in normal skeletal muscle. Colon carcinoma cell lines stably
      overexpressing Mirk proliferated in serum-free medium, but the mechanism of Mirk
      action is unknown. DCoHm (dimerization cofactor of hepatocyte nuclear factor
      1alpha ( HNF1alpha) from muscle), a novel gene of the DCoH family with 78% amino
      acid identity to DCoH, was identified as a Mirk-binding protein by yeast two
      hybrid analysis and cloned. Mirk co-immunoprecipitated with DCoHm and bound to
      DCoHm in glutathione S-transferase pull-down assays. DCoH stabilizes HNF1alpha as
      a dimer and enhances its transcriptional activity on the beta-fibrinogen promoter
      reporter, and DCoHm had similar activity. Mirk enhanced HNF1alpha transcriptional
      activity in a dose-dependent manner, whereas two kinase-inactive Mirk mutants and
      a Mirk N-terminal deletion mutant did not. Mirk, DCoHm, and HNF1alpha formed a
      complex. Mirk bound to a specific region within the CREB-binding protein-binding
      region of HNF1alpha and phosphorylated HNF1alpha at a site adjacent to the Mirk
      binding region. Conversely, the HNF1alpha binding domain was located within the
      first five conserved kinase subdomains of Mirk. Mirk co-immunoprecipitated with
      the MAPK kinase MKK3, an upstream activator of p38. MKK3 enhanced Mirk kinase
      activity and the transcriptional activation of HNF1alpha by Mirk, suggesting that
      Mirk, like p38, is activated by certain environmental stress agents. The Mirk
      binding protein DCoH has been shown to be selectively expressed in colon
      carcinomas but not in normal tissue. Mirk may function as an HNF1alpha
      transcriptional activator in response to an MKK3-mediated stress signal, and the
      selective expression of DCoH could restrict the Mirk response to carcinoma cells.

PMID- 11980911
TI  - Participation of two members of the very long-chain acyl-CoA synthetase family in
      bile acid synthesis and recycling.
AB  - Bile acids are synthesized de novo in the liver from cholesterol and conjugated
      to glycine or taurine via a complex series of reactions involving multiple
      organelles. Bile acids secreted into the small intestine are efficiently
      reabsorbed and reutilized. Activation by thioesterification to CoA is required at
      two points in bile acid metabolism. First, 3alpha,7alpha,12alpha-trihydroxy-5beta
      cholestanoic acid, the 27-carbon precursor of cholic acid, must be activated to
      its CoA derivative before side chain cleavage via peroxisomal beta-oxidation.
      Second, reutilization of cholate and other C24 bile acids requires reactivation
      prior to re-conjugation. We reported previously that homolog 2 of very long-chain
      acyl-CoA synthetase (VLCS) can activate cholate (Steinberg, S. J., Mihalik, S.
      J., Kim, D. G., Cuebas, D. A., and Watkins, P. A. (2000) J. Biol. Chem. 275,
      15605-15608). We now show that this enzyme also activates chenodeoxycholate, the
      secondary bile acids deoxycholate and lithocholate, and 3alpha,7alpha,12alpha
      trihydroxy-5beta-cholestanoic acid. In contrast, VLCS activated
      3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoate, but did not utilize any of
      the C24 bile acids as substrates. We hypothesize that the primary function of
      homolog 2 is in the reactivation and recycling of C24 bile acids, whereas VLCS
      participates in the de novo synthesis pathway. Results of in situ hybridization,
      topographic orientation, and inhibition studies are consistent with the proposed
      roles of these enzymes in bile acid metabolism.

PMID- 11980912
TI  - Methanococcus jannaschii uses a pyruvoyl-dependent arginine decarboxylase in
      polyamine biosynthesis.
AB  - The genome sequence of the hyperthermophilic methanogen Methanococcus jannaschii
      contains homologs of most genes required for spermidine polyamine biosynthesis.
      Yet genomes from neither this organism nor any other euryarchaeon have orthologs
      of the pyridoxal 5'-phosphate-dependent ornithine or arginine decarboxylase
      genes, required to produce putrescine. Instead, as shown here, these organisms
      have a new class of arginine decarboxylase (PvlArgDC) formed by the self-cleavage
      of a proenzyme into a 5-kDa subunit and a 12-kDa subunit that contains a reactive
      pyruvoyl group. Although this extremely thermostable enzyme has no significant
      sequence similarity to previously characterized proteins, conserved active site
      residues are similar to those of the pyruvoyl-dependent histidine decarboxylase
      enzyme, and its subunits form a similar (alphabeta)(3) complex. Homologs of
      PvlArgDC are found in several bacterial genomes, including those of Chlamydia
      spp., which have no agmatine ureohydrolase enzyme to convert agmatine
      (decarboxylated arginine) into putrescine. In these intracellular pathogens,
      PvlArgDC may function analogously to pyruvoyl-dependent histidine decarboxylase;
      the cells are proposed to import arginine and export agmatine, increasing the pH
      and affecting the host cell's metabolism. Phylogenetic analysis of Pvl- ArgDC
      proteins suggests that this gene has been recruited from the euryarchaeal
      polyamine biosynthetic pathway to function as a degradative enzyme in bacteria.

PMID- 11980913
TI  - The glutamine commute: take the N line and transfer to the A.
AB  - The transfer of glutamine between cells contributes to signaling as well as to
      metabolism. The recent identification and characterization of the system N and A
      family of transporters has begun to suggest mechanisms for the directional
      transfer of glutamine, and should provide ways to test its physiological
      significance in diverse processes from nitrogen to neurotransmitter release.

PMID- 11980914
TI  - Human Speedy: a novel cell cycle regulator that enhances proliferation through
      activation of Cdk2.
AB  - The decision for a cell to self-replicate requires passage from G1 to S phase of
      the cell cycle and initiation of another round of DNA replication. This
      commitment is a critical one that is tightly regulated by many parallel pathways.
      Significantly, these pathways converge to result in activation of the cyclin
      dependent kinase, cdk2. It is, therefore, important to understand all the
      mechanisms regulating cdk2 to determine the molecular basis of cell progression.
      Here we report the identification and characterization of a novel cell cycle
      gene, designated Speedy (Spy1). Spy1 is 40% homologous to the Xenopus cell cycle
      gene, X-Spy1. Similar to its Xenopus counterpart, human Speedy is able to induce
      oocyte maturation, suggesting similar biological characteristics. Spy1 mRNA is
      expressed in several human tissues and immortalized cell lines and is only
      expressed during the G1/S phase of the cell cycle. Overexpression of Spy1 protein
      demonstrates that Spy1 is nuclear and results in enhanced cell proliferation. In
      addition, flow cytometry profiles of these cells demonstrate a reduction in G1
      population. Changes in cell cycle regulation can be attributed to the ability of
      Spy1 to bind to and prematurely activate cdk2 independent of cyclin binding. We
      demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2
      activation. Furthermore, abrogation of Spy1 expression, through the use of siRNA,
      demonstrates that Spy1 is an essential component of cell proliferation pathways.
      Hence, human Speedy is a novel cell cycle protein capable of promoting cell
      proliferation through the premature activation of cdk2 at the G1/S phase
      transition.

PMID- 11980915
TI  - Dislocation and degradation from the ER are regulated by cytosolic stress.
AB  - Akey step in ER-associated degradation (ERAD) is dislocation of the substrate
      protein from the ER into the cytosol to gain access to the proteasome. Very
      little is known about how this process is regulated, especially in the case of
      polytopic proteins. Using pulse-chase analysis combined with subcellular
      fractionation, we show that connexins, the four transmembrane structural
      components of gap junctions, can be chased in an intact form from the ER membrane
      into the cytosol of proteasome inhibitor-treated cells. Dislocation of
      endogenously expressed connexin from the ER was reduced 50-80% when the cytosolic
      heat shock response was induced by mild oxidative or thermal stress, but not by
      treatments that instead upregulate the ER unfolded protein response. Cytosolic
      but not ER stresses slowed the normally rapid degradation of connexins, and led
      to a striking increase in gap junction formation and function in otherwise
      assembly-inefficient cell types. These treatments also inhibited the dislocation
      and turnover of a connexin-unrelated ERAD substrate, unassembled major
      histocompatibility complex class I heavy chain. Our findings demonstrate that
      dislocation is negatively regulated by physiologically relevant, nonlethal
      stress. They also reveal a previously unrecognized relationship between cytosolic
      stress and intercellular communication.

PMID- 11980916
TI  - Characterization of a mammalian Golgi-localized protein complex, COG, that is
      required for normal Golgi morphology and function.
AB  - Multiprotein complexes are key determinants of Golgi apparatus structure and its
      capacity for intracellular transport and glycoprotein modification. Three
      complexes that have previously been partially characterized include (a) the Golgi
      transport complex (GTC), identified in an in vitro membrane transport assay, (b)
      the ldlCp complex, identified in analyses of CHO cell mutants with defects in
      Golgi-associated glycosylation reactions, and (c) the mammalian Sec34 complex,
      identified by homology to yeast Sec34p, implicated in vesicular transport. We
      show that these three complexes are identical and rename them the conserved
      oligomeric Golgi (COG) complex. The COG complex comprises four previously
      characterized proteins (Cog1/ldlBp, Cog2/ldlCp, Cog3/Sec34, and Cog5/GTC-90),
      three homologues of yeast Sec34/35 complex subunits (Cog4, -6, and -8), and a
      previously unidentified Golgi-associated protein (Cog7). EM of ldlB and ldlC
      mutants established that COG is required for normal Golgi morphology. "Deep etch"
      EM of purified COG revealed an approximately 37-nm-long structure comprised of
      two similarly sized globular domains connected by smaller extensions.
      Consideration of biochemical and genetic data for mammalian COG and its yeast
      homologue suggests a model for the subunit distribution within this complex,
      which plays critical roles in Golgi structure and function.

PMID- 11980917
TI  - Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion
      degradation substrate that blocks proteasomal degradation.
AB  - Loss of neurons in neurodegenerative diseases is usually preceded by the
      accumulation of protein deposits that contain components of the
      ubiquitin/proteasome system. Affected neurons in Alzheimer's disease often
      accumulate UBB(+1), a mutant ubiquitin carrying a 19-amino acid C-terminal
      extension generated by a transcriptional dinucleotide deletion. Here we show that
      UBB(+1) is a potent inhibitor of ubiquitin-dependent proteolysis in neuronal
      cells, and that this inhibitory activity correlates with induction of cell cycle
      arrest. Surprisingly, UBB(+1) is recognized as a ubiquitin fusion degradation
      (UFD) proteasome substrate and ubiquitinated at Lys29 and Lys48. Full blockade of
      proteolysis requires both ubiquitination sites. Moreover, the inhibitory effect
      was enhanced by the introduction of multiple UFD signals. Our findings suggest
      that the inhibitory activity of UBB(+1) may be an important determinant of
      neurotoxicity and contribute to an environment that favors the accumulation of
      misfolded proteins.

PMID- 11980919
TI  - Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from
      the analysis of mutant mice.
AB  - Trophic factor deprivation (TFD)-induced apoptosis in sympathetic neurons
      requires macromolecular synthesis-dependent BAX translocation, cytochrome c (cyt
      c) release, and caspase activation. Here, we report the contributions of other
      intrinsic and extrinsic pathway signals to these processes. Sympathetic neurons
      expressed all antiapoptotic BCL-2 proteins examined, yet expressed only certain
      BH3-only and multidomain proapoptotic BCL-2 family members. All coexpressed
      proapoptotic proteins did not, however, exhibit functional redundancy or
      compensatory expression, at least in the Bax-/-, Bak-/-, Bim-/-, Bid-/-, and Bad
      /- neurons examined. Although the subcellular distribution or posttranslational
      modification of certain BCL-2 proteins changed with TFD, neither transcriptional
      nor posttranslational mechanisms regulated the expression or subcellular
      localization of BID, BAD, or BAK in this paradigm. Despite modest induction of
      Fas and FasL expression, Fas-mediated signaling did not contribute to TFD-induced
      apoptosis in sympathetic neurons. Similar findings were obtained with K+
      withdrawal-induced apoptosis in cerebellar granule neurons, a model for activity
      dependent neuronal survival in the CNS. Thus, expression alone does not guarantee
      functional redundancy (or compensation) among BCL-2 family members, and, at least
      in some cells, extrinsic pathway signaling and certain BH3-only proteins (i.e.,
      BID and BAD) do not contribute to BAX-dependent cyt c release or apoptosis caused
      by TFD.

PMID- 11980918
TI  - Wnt signaling promotes oncogenic transformation by inhibiting c-Myc-induced
      apoptosis.
AB  - Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with
      numerous human cancers and often correlates with the overexpression or
      amplification of the c-myc oncogene. Paradoxical to the cellular transformation
      potential of c-Myc is its ability to also induce apoptosis. Using an inducible c
      MycER expression system, we found that Wnt/beta-catenin signaling suppressed
      apoptosis by inhibiting c-Myc-induced release of cytochrome c and caspase
      activation. Both cyclooxygenase 2 and WISP-1 were identified as effectors of the
      Wnt-mediated antiapoptotic signal. Soft agar assays showed that neither c-Myc nor
      Wnt-1 alone was sufficient to induce cellular transformation, but that Wnt and c
      Myc coordinated in inducing transformation. Furthermore, coexpression of Wnt-1
      and c-Myc induced high-frequency and rapid tumor growth in nude mice. Extensive
      apoptotic bodies were characteristic of c-Myc-induced tumors, but not tumors
      induced by coactivation of c-Myc and Wnt-1, indicating that the antiapoptotic
      function of Wnt-1 plays a critical role in the synergetic action between c-Myc
      and Wnt-1. These results elucidate the molecular mechanisms by which Wnt/beta
      catenin inhibits apoptosis and provide new insight into Wnt signaling-mediated
      oncogenesis.

PMID- 11980920
TI  - DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic
      vesicles during programmed cell death.
AB  - Death-associated protein kinase (DAPk) and DAPk-related protein kinase (DRP)-1
      proteins are Ca+2/calmodulin-regulated Ser/Thr death kinases whose precise roles
      in programmed cell death are still mostly unknown. In this study, we dissected
      the subcellular events in which these kinases are involved during cell death.
      Expression of each of these DAPk subfamily members in their activated forms
      triggered two major cytoplasmic events: membrane blebbing, characteristic of
      several types of cell death, and extensive autophagy, which is typical of
      autophagic (type II) programmed cell death. These two different cellular outcomes
      were totally independent of caspase activity. It was also found that dominant
      negative mutants of DAPk or DRP-1 reduced membrane blebbing during the p55/tumor
      necrosis factor receptor 1-induced type I apoptosis but did not prevent nuclear
      fragmentation. In addition, expression of the dominant negative mutant of DRP-1
      or of DAPk antisense mRNA reduced autophagy induced by antiestrogens, amino acid
      starvation, or administration of interferon-gamma. Thus, both endogenous DAPk and
      DRP-1 possess rate-limiting functions in these two distinct cytoplasmic events.
      Finally, immunogold staining showed that DRP-1 is localized inside the autophagic
      vesicles, suggesting a direct involvement of this kinase in the process of
      autophagy.

PMID- 11980921
TI  - Defective Rac-mediated proliferation and survival after targeted mutation of the
      beta1 integrin cytodomain.
AB  - Cell matrix adhesion is required for cell proliferation and survival. Here we
      report that mutation by gene targeting of the cytoplasmic tail of beta1 integrin
      leads to defective proliferation and survival both in vivo and in vitro. Primary
      murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display
      defective cell cycle coupled to impaired activation of the FAK-PI3K-Akt and Rac
      JNK signaling pathways. Expression in homozygous MEFs of a constitutively active
      form of Rac is able to rescue proliferation, survival, and JNK activation.
      Moreover, although showing normal Erk phosphorylation, mutant cells fail to
      display Erk nuclear translocation upon fibronectin adhesion. However, expression
      of the constitutively activated form of Rac restores Erk nuclear localization,
      suggesting that adhesion-dependent Rac activation is necessary to integrate
      signals directed to promote MAPK activity. Altogether, our data provide the
      evidence for an epistatic interaction between the beta1 integrin cytoplasmic
      domain and Rac, and indicate that this anchorage-dependent signaling pathway is
      crucial for cell growth control.

PMID- 11980922
TI  - Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially
      modulate T cell behavior.
AB  - Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both
      positively and negatively. We found that these opposing responses arise from
      interactions of TSP1 with two different T cell receptors. The integrin
      alpha4beta1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and
      was required for stimulation of T cell adhesion, chemotaxis, and matrix
      metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells
      depended on the activation state of alpha4beta1 integrin, and TSP1 inhibited
      interaction of activated alpha4beta1 integrin on T cells with its counter
      receptor vascular cell adhesion molecule-1. The alpha4beta1 integrin recognition
      site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence
      replicated the alpha4beta1 integrin-dependent activities of TSP1. The beta1
      integrin recognition sites in TSP1, however, were neither necessary nor
      sufficient for inhibition of T cell proliferation and T cell antigen receptor
      signaling by TSP1. A second TSP1 receptor, CD47, was not required for some
      stimulatory responses to TSP1 but played a significant role in its T cell antigen
      receptor antagonist and antiproliferative activities. Modulating the relative
      expression or function of these two TSP receptors could therefore alter the
      direction or magnitude of T cell responses to TSPs.

PMID- 11980923
TI  - Cosignaling of NCAM via lipid rafts and the FGF receptor is required for
      neuritogenesis.
AB  - The neural cell adhesion molecule (NCAM) has been reported to stimulate
      neuritogenesis either via nonreceptor tyrosine kinases or fibroblast growth
      factor (FGF) receptor. Here we show that lipid raft association of NCAM is
      crucial for activation of the nonreceptor tyrosine kinase pathway and induction
      of neurite outgrowth. Transfection of hippocampal neurons of NCAM-deficient mice
      revealed that of the three major NCAM isoforms only NCAM140 can act as a
      homophilic receptor that induces neurite outgrowth. Disruption of NCAM140 raft
      association either by mutation of NCAM140 palmitoylation sites or by lipid raft
      destruction attenuates activation of the tyrosine focal adhesion kinase and
      extracellular signal-regulated kinase 1/2, completely blocking neurite outgrowth.
      Likewise, NCAM-triggered neurite outgrowth is also completely blocked by a
      specific FGF receptor inhibitor, indicating that cosignaling via raft-associated
      kinases and FGF receptor is essential for neuritogenesis.

PMID- 11980924
TI  - Risk assessment models and contamination management: implications for broad-range
      ribosomal DNA PCR as a diagnostic tool in medical bacteriology.

PMID- 11980925
TI  - Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid
      assays.
AB  - Human cytomegalovirus (CMV) continues to be a significant cause of morbidity and
      mortality among transplant recipients. Molecular assays have been developed for
      the detection and quantification of CMV nucleic acid. In evaluating the clinical
      utility of these assays, correlations with clinical outcome are essential. The
      Amplicor CMV Monitor and NucliSens CMV pp67 tests were compared to the CMV
      antigenemia assay for 45 transplant recipients and 1 patient with Wegener's
      granulomatosis. Twenty-three patients remained antigenemia negative throughout
      the monitoring period, none of whom developed CMV disease. In this patient group,
      both the Amplicor and NucliSens assays showed very high specificity; only 1 of
      the 324 specimens assayed by NucliSens and none of the 303 specimens assayed by
      Amplicor were positive. Twenty-three patients were antigenemia positive during
      the monitoring period, 12 of whom developed 13 episodes of symptomatic CMV
      disease. In this patient group, the NucliSens assay was positive at or before the
      development of symptoms in 12 of the 13 episodes of CMV disease. All eight
      patients with symptomatic CMV disease who were tested by the Amplicor assay were
      positive at or before the development of disease. For the 11 asymptomatic
      patients, the NucliSens assay was positive less frequently than the antigenemia
      or Amplicor assays. The NucliSens assay was more likely to be positive at higher
      antigenemia or viral load levels. Both the NucliSens and Amplicor assays appear
      to have clinical utility in monitoring patients for CMV disease.

PMID- 11980926
TI  - Recombinant nucleoprotein-based enzyme-linked immunosorbent assay for detection
      of immunoglobulin G antibodies to Crimean-Congo hemorrhagic fever virus.
AB  - The full-length nucleoprotein of Crimean-Congo hemorrhagic fever virus (CCHFV;
      482 amino acid residues) was expressed as a His-tagged recombinant protein (His
      CCHFV rNP) in the baculovirus system. The His-CCHFV rNP was efficiently expressed
      in insect cells and purified by Ni(2+) column chromatography. Using this
      substrate, an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA)
      was developed. We evaluated the sensitivity and specificity of the IgG ELISA,
      using serum samples previously determined to be antibody positive or negative by
      immunofluorescence tests on CCHFV-infected Vero E6 cells. We found very good
      correlation between the two tests: 87% for the positive sera (13 of 15) and 99%
      for the negative sera (107 of 108). These results indicate that the new IgG ELISA
      using His-CCHFV rNP has high sensitivity and specificity for detecting CCHFV
      antibodies. The CCHF patients' sera with high titers reacted only with the NP
      fragment containing amino acid residues between 201 and 306 in Western blotting.
      It is known that amino acid homologies are high in this region among various
      isolates. Thus, it is expected that this ELISA can detect antibodies not only for
      Chinese strains of CCHFV but also for other strains circulating in the world.
      These results suggest that the IgG ELISA system developed with the recombinant
      CCHFV NP is a valuable tool for diagnosis and epidemiological investigations of
      CCHFV infections.

PMID- 11980927
TI  - Variable-number tandem repeat typing of Mycobacterium tuberculosis isolates with
      low copy numbers of IS6110 by using mycobacterial interspersed repetitive units.
AB  - A study set of 180 Mycobacterium tuberculosis and Mycobacterium bovis isolates
      having low copy numbers of IS6110 were genotyped using the recently introduced
      method based on the variable-number tandem repeats of mycobacterial interspersed
      repetitive units (MIRU-VNTR). The results were compared with results of the more
      commonly used methods, IS6110 restriction fragment length polymorphism (RFLP) and
      spoligotyping. The isolates were collected in Michigan from 1996 to 1999 as part
      of a project to genotype all isolates from new cases of tuberculosis in the
      state. Twelve MIRU loci were amplified, and the amplicons were analyzed by
      agarose gel electrophoresis to determine the copy number at each MIRU locus. MIRU
      VNTR produced more distinct patterns (80 patterns) than did IS6110 RFLP (58
      patterns), as would be expected in this study set. Spoligotyping identified 59
      patterns. No single method defined all unique isolates, and the combination of
      all three typing methods generated 112 distinct patterns identifying 90 unique
      isolates and 90 isolates in 22 clusters. The results confirm the potential
      utility of MIRU-VNTR typing and show that typing with multiple methods is
      required to attain maximum specificity.

PMID- 11980928
TI  - Comparison of eleven commercial tests for Chlamydia pneumoniae-specific
      immunoglobulin G in asymptomatic healthy individuals.
AB  - The seroprevalence of anti-Chlamydia pneumoniae-specific immunoglobulin G (IgG)
      antibodies is high in the adult population. Experience is required to perform a
      microimmunofluorescence test (MIF), the current "gold standard" for serological
      diagnosis, and the assay still lacks standardization. Partially automated enzyme
      linked immunosorbent assays (ELISAs) and enzyme immunoassays (EIAs), which are
      more standardized and for which the reading of results is less subjective, have
      been developed. The different commercially available serological tests differ in
      their sensitivities and specificities, depending primarily on the antigen used.
      Therefore, we evaluated 11 different tests (10 were species specific, 1 was genus
      specific) for IgG antibodies using serum samples of 80 apparently healthy
      volunteers. The interpretation of the results was based on the results of the
      gold standard, MIF: a sample was judged positive if it was positive by at least
      three of the four different MIFs. Based on this internal standard, we found that
      71% of the samples were positive, while 8% were false positive by some tests. The
      correlations between the results of the different MIFs ranged from 83 to 99%, and
      the correlations between the results of the MIFs and the different ELISAs and
      EIAs ranged from 78 to 98%. Comparison of the IgG titers measured by MIF showed
      good agreement (r = 0.76 to 0.91). This analysis revealed that some ELISAs and
      EIAs fail to detect low IgG titers. The specificities of the species-specific
      tests varied from 95 to 100%, and the sensitivities varied from 58 to 100%. These
      results indicate that serological assays for the detection of anti-C. pneumoniae
      specific IgG vary greatly in their sensitivities and specificities. MIF must
      still be considered the best method for the detection of IgG in apparently
      healthy subjects, but the sensitivities and specificities of new ELISAs
      approximate those of MIFs.

PMID- 11980929
TI  - Temperature-mediated heteroduplex analysis performed by using denaturing high
      performance liquid chromatography to identify sequence polymorphisms in
      Mycobacterium tuberculosis complex organisms.
AB  - PCR products containing sequence polymorphisms were prepared from six
      mycobacterial genes, denatured, mixed with reference PCR products, and
      reannealed; the mixtures were then examined with a denaturing high-performance
      liquid chromatography system (WAVE) equipped with a temperature-controlled
      alkalated polystyrene divinyl benzene column. Mismatching of bases in
      heteroduplexes of the PCR products causes elution patterns of the DNA from the
      column to be altered. The six mycobacterial genes studied were oxyR, in which a
      specific polymorphism (G(1031)A) is found only in certain species of the
      Mycobacterium tuberculosis complex, and five genes in which mutations associated
      with antituberculosis drug resistance have been found. The resistance genes (with
      affected drug and PCR product sizes given parenthetically) were rpoB (rifampin;
      258 bp), katG (isoniazid; 205 bp), pncA (pyrazinamide; 579 bp); rpsL
      (streptomycin; 196 bp), and embB (ethambutol; 185 bp). Elution patterns of
      heteroduplexes of all 20 polymorphisms studied shifted detectably at column
      temperatures ranging from 65.3 to 68 degrees C and elution times of 3.5 to 6 min.
      These results show that temperature-mediated heteroduplex analysis is a
      potentially useful genotypic screen for mutations associated with
      antituberculosis drug resistance and for the G(1031)A polymorphism in oxyR. The
      method may allow users to detect novel as well as heterogeneous mutations without
      using expensive kits or detection labels.

PMID- 11980930
TI  - Detection of ethambutol-resistant Mycobacterium tuberculosis strains by multiplex
      allele-specific PCR assay targeting embB306 mutations.
AB  - We describe a multiplex allele-specific (MAS)-PCR assay to detect simultaneously
      mutations in the first and third bases of the embB gene codon 306ATG. These
      mutations are known to confer ethambutol (EMB) resistance in the majority of
      clinical Mycobacterium tuberculosis isolates worldwide. The mutated bases are
      revealed depending on the presence or absence of the respective indicative
      fragments amplified from the embB306 wild-type allele. Initially optimized on
      purified DNA samples, the assay was tested on crude cell lysates and auramine
      stained sputum slide DNA preparations with the same reproducibility and
      interpretability of the generated profiles in agarose gel electrophoresis. Since
      EMB resistance is generally linked to multiple-drug resistance (MDR), the MAS-PCR
      assay for EMB resistance detection can be used in clinical laboratory practice in
      areas with a high prevalence and a high transmission rate of MDR-EMB-resistant
      tuberculosis.

PMID- 11980931
TI  - 18S ribosomal DNA typing and tracking of Acanthamoeba species isolates from
      corneal scrape specimens, contact lenses, lens cases, and home water supplies of
      Acanthamoeba keratitis patients in Hong Kong.
AB  - We examined partial 18S ribosomal DNA (Rns) sequences of Acanthamoeba isolates
      cultured in a study of microbial keratitis in Hong Kong. Sequence differences
      were sufficient to distinguish closely related strains and were used to examine
      links between strains obtained from corneal scrape specimens, contact lenses,
      lens cases, lens case solutions, and home water-supply faucets of patients with
      Acanthamoeba. We also looked for evidence of mixed infections. Identification of
      Acanthamoeba Rns genotypes was based on sequences of approximately 113 bp within
      the genus-specific amplicon ASA.S1. This permitted genotype identification by
      using nonaxenic cultures. Of 13 specimens obtained from corneal scrapes, contact
      lenses, lens cases, or lens case solutions, 12 were Rns genotype T4 and the
      remaining one was Rns genotype T3. The sequences of corneal scrape specimens of
      two patients also were the same as those obtained from their contact lenses or
      lens case specimens. A possible triple-strain infection was indicated by three
      different T4 sequences in cultures from one patient's lenses. Although faucet
      water used by patients to clean their lenses is a possible source of infections,
      specimens isolated from the faucets at two Acanthamoeba keratitis patients' homes
      differed from their corneal scrape or lens specimens. The overall results
      demonstrate the potential of this Rns region for tracking Acanthamoeba keratitis
      strains in infections and for distinguishing single-strain and closely related
      multiple-strain infections even when other microorganisms might be present with
      the cultured specimens. They also confirm the predominance of Rns genotype T4
      strains in Acanthamoeba keratitis infections.

PMID- 11980933
TI  - Molecular epidemiology and drug resistance of Mycobacterium tuberculosis isolates
      from Ethiopian pulmonary tuberculosis patients with and without human
      immunodeficiency virus infection.
AB  - We have analyzed the molecular epidemiology and drug resistance of 121
      Mycobacterium tuberculosis isolates from consecutive patients with culture
      positive pulmonary tuberculosis attending a university hospital outpatient
      department in Addis Ababa, Ethiopia. Restriction fragment length polymorphism
      analysis and spoligotyping were used to analyze the DNA fingerprinting patterns.
      Fifty-one (41.2%) of the isolates were found in 13 clusters with two or more
      identical DNA patterns. Two such clusters contained 49.0% of all clustered
      isolates. In a multivariate logistic regression model, human immunodeficiency
      virus (HIV)-positive serostatus was significantly associated with clustering of
      isolates for patients of both sexes (odds ratio [OR], 2.55; 95% confidence
      interval [CI], 1.17 to 5.80). There was a trend toward increased clustering of
      isolates from tuberculous women residing in Addis Ababa (OR, 2.10; 95% CI, 0.85
      to 5.25). In total, 17 of 121 isolates (14.0%) were resistant to one or more of
      the antituberculosis drugs isoniazid (8.3%), streptomycin (7.4%), rifampin
      (2.5%), and ethambutol (1.7%). The high rate of drug-resistant isolates (29.6%)
      coincided with the peak prevalence of HIV infection (77.8%) in patients 35 to 44
      years old. The majority (62.5%) of resistant isolates in this group were found
      within clusters. The simultaneous accumulation of certain bacterial clones in a
      patient population likely reflects recent transmission. Hence, we conclude that
      tuberculosis is commonly caused by recent infection with M. tuberculosis in HIV
      positive Ethiopian patients. Furthermore, with the rapidly increasing prevalence
      of HIV infection in Ethiopia, the burden of tuberculosis, including drug
      resistant tuberculosis, is likely to increase. Strengthening of classical
      tuberculosis control measures by promoting active case finding among HIV-positive
      adults with tuberculosis is warranted to reduce rates of transmission.

PMID- 11980934
TI  - Evaluation of two nested PCR assays for detection of Histoplasma capsulatum DNA
      in human tissue.
AB  - In order to evaluate the diagnostic relevance of two nested PCR assays for
      diagnosis of histoplasmosis in clinical specimens, 100 paraffin-embedded biopsy
      specimens were examined. Upon microscopy of tissue, 50 biopsy specimens were
      histoplasma positive and 50 were negative. Due to destruction by formalin
      fixation, successful extraction of amplifiable human DNA was limited to 29 and 33
      samples, respectively. A product of the Histoplasma capsulatum nested PCR assay
      targeting the gene encoding the unique fungal 100-kDa-like protein was detected
      in 20 histopathologically positive biopsy specimens but in none of the
      microscopically negative samples. Sequencing revealed that all 20 products of 210
      bp were identical to the sequence of H. capsulatum in the GenBank database. In
      contrast, the nested PCR assay targeting the fungal 18S rRNA genes amplified
      products in 26 histopathologically positive but also in 18 microscopically
      negative biopsy specimens. However, sequencing revealed that only 20 of these 44
      PCR products (231 bp) were identical to the sequence of H. capsulatum. The
      remaining 24 sequences were homologous to those of several Euascomycetes. These
      PCR products were detected only in tissues possibly colonized by nonpathogenic
      fungi, possibly causing these nonspecific amplifications. The detection limit of
      both H. capsulatum nested PCR assays was 1 to 5 fungal cells per sample. The two
      assays were similarly sensitive in identifying H. capsulatum. In this preliminary
      study, the novel 100-kDa-like-protein gene nested PCR revealed a specificity of
      100% without requiring sequencing, which was necessary for identification of the
      18S ribosomal DNA nested PCR products in order to avoid a high rate of false
      positive results.

PMID- 11980935
TI  - Disseminated toxoplasmosis, resulting from infection of allograft, after
      orthotopic liver transplantation: usefulness of quantitative PCR.
AB  - Disseminated toxoplasmosis is a life-threatening disease in liver transplant
      recipients that can result from an organ-transmitted infection. We report here a
      case of fatal disseminated toxoplasmosis after orthotopic liver transplantation
      from a seropositive donor (immunoglobulin G [IgG](+) and IgM(-)) in a patient who
      was nonimmune for toxoplasmosis prior to transplantation. Quantitative PCR
      analyses of various clinical specimens, including serum samples, appeared
      retrospectively to be a valuable diagnostic tool that might guide therapeutic
      attitudes.

PMID- 11980936
TI  - Characterization of Mycobacterium tuberculosis complex isolates from the
      cerebrospinal fluid of meningitis patients at six fever hospitals in Egypt.
AB  - Mycobacterium tuberculosis complex isolates from cerebrospinal fluid of 67
      meningitis patients were obtained from six fever hospitals in Egypt. One M. bovis
      and 66 M. tuberculosis isolates were identified by PCR-restriction fragment
      length polymorphism (RFLP) analysis of oxyR. Among the M. tuberculosis isolates,
      53 unique strain types (with 3 to 16 copies of IS6110) were found by RFLP
      analyses. Nine clusters (eight with two isolates each and one with six isolates)
      were also found. Thirty-six spoligotypes, including at least 10 that have been
      previously reported from other countries, were also observed. Forty-one (62.1%)
      of the isolates were in spoligotype clusters, and 22 (33%) of the isolates were
      in RFLP clusters. Fifty-one of the isolates were susceptible in vitro to all of
      the antituberculosis drugs tested, 11 were monoresistant to capreomycin,
      rifampin, isoniazid (INH), pyrazinamide, or streptomycin (STR), 4 were resistant
      to STR and INH, and 1 was resistant to STR, INH, and ethambutol.

PMID- 11980932
TI  - Multilocus sequence typing for characterization of clinical and environmental
      salmonella strains.
AB  - Multilocus sequence typing (MLST) based on the 16S RNA, pduF, glnA, and manB
      genes was developed for Salmonella, and its discriminatory ability was compared
      to those of pulsed-field gel electrophoresis (PFGE) and serotyping. PFGE
      differentiated several strains undifferentiable by serotyping, and 78 distinct
      PFGE types were identified among 231 Salmonella isolates grouped into 22
      serotypes and 12 strains of undetermined serotype. The strains of several PFGE
      types were further differentiated by MLST, which suggests that the discriminatory
      ability of MLST for the typing of Salmonella is better than that of serotyping
      and/or PFGE typing. manB-based sequence typing identified two distinct genetic
      clusters containing 32 of 54 (59%) clinical isolates whose manB gene sequences
      were analyzed. The G+C contents and Splitstree analysis of the manB, glnA, and
      pduF genes of Salmonella indicated that the genes differ in their evolutionary
      origins and that recombination played a significant role in their evolution.

PMID- 11980937
TI  - Comparison of second- and third-generation enzyme immunoassays for detecting
      antibodies to hepatitis C virus.
AB  - Supplemental assays, such as recombinant immunoblot assays (RIBA), are used to
      confirm detection of antibodies to hepatitis C virus (HCV). However, due to their
      expense, they are not widely used in developing countries. The purpose of our
      study was to compare the results of second- and third-generation (G2 and G3,
      respectively) enzyme immunoassays (EIAs) and to resolve discordant results by
      using a supplemental assay to assess the reliability of G2 and G3 EIAs to confirm
      anti-HCV antibody-positive results. We performed both G2 and G3 EIAs for anti-HCV
      antibodies on 1,134 serum samples collected during the 2nd year of a longitudinal
      community-based study in Egypt; 35 samples with discordant results were tested by
      Abbott Laboratories Micro-Particle Immunoassay (M-EIA) and RIBA. Viremia was
      determined with an in-house nested reverse transcriptase PCR (RT-PCR) to detect
      HCV RNA. Concordance between the two assays (G2/G3) was 96.9%; 87 (7.7%) samples
      were positive and 1,012 (89.2%) were negative by both assays. For 17 samples, the
      discordant results were G2 assay negative and G3 assay positive, and for 18
      samples, the discordant results were G2 assay positive and G3 assay negative.
      Among the 17 G2 assay-negative and G3 assay-positive samples, 15 were M-EIA
      positive and 7 were PCR positive. Among the 18 G2 assay-positive and G3 assay
      negative samples, 2 were M-EIA positive and none were PCR positive. RIBA results
      from 24 discordant samples showed 87.5% agreement with the G3 EIA, 12.5%
      agreement with the G2 EIA, and 95.8% agreement with M-EIA. Eleven samples were
      indeterminate by RIBA and excluded from this analysis. Based on RIBA results, the
      sensitivity of the G3 EIA was 99%, compared to 89.8% for the G2 EIA, while the
      specificity of the G3 EIA was 99.8%, compared to 98.9% for the G2 EIA. These
      results show that the reliability of the G3 EIA in screening these sera is
      excellent, and the G3 assay can be used in the absence of supplemental tests
      where resources are limited. RIBA appears not to have advantages over the less
      expensive M-EIA screening assay. The main disadvantage of RIBA is the occurrence
      of indeterminate results, especially among problematic samples. Samples giving
      discordant results in multiple assays are often indeterminate with the RIBA.

PMID- 11980938
TI  - Comparison of four antiseptic preparations for skin in the prevention of
      contamination of percutaneously drawn blood cultures: a randomized trial.
AB  - A number of skin antiseptics have been used to prevent the contamination of blood
      cultures, but the comparative efficacies of these agents have not been
      extensively evaluated. We therefore sought to compare the efficacy of four skin
      antiseptics in preventing blood culture contamination in a randomized, crossover,
      investigator-blinded study conducted in an emergency department and the inpatient
      wards of a university hospital. The patient group included all patients from whom
      blood samples were obtained percutaneously for culture. Skin antisepsis was
      performed with 10% povidone-iodine, 70% isopropyl alcohol, tincture of iodine, or
      povidone-iodine with 70% ethyl alcohol (i.e., Persist). The blood culture
      contamination rate associated with each antiseptic was then determined. A total
      of 333 (2.62%) of 12,692 blood cultures were contaminated during the study period
      compared to 413 (3.21%) of 12,859 blood cultures obtained during the previous 12
      month period (relative risk = 0.82; 95% confidence interval, 0.71 to 0.94; P =
      0.006). During the study, the contamination rates were determined to be 2.93%
      with povidone-iodine, 2.58% with tincture of iodine, 2.50% with isopropyl
      alcohol, and 2.46% with Persist (P = 0.62). We detected no significant
      differences in the blood culture contamination rates among these four
      antiseptics, although there was some evidence suggesting greater efficacy among
      the alcohol-containing antiseptics. Among the evaluated antiseptics, isopropyl
      alcohol may be the optimal antiseptic for use prior to obtaining blood for
      culture, given its convenience, low cost, and tolerability.

PMID- 11980939
TI  - Real-time PCR for detection and quantitation of leishmania in mouse tissues.
AB  - Leishmania spp. are intracellular protozoan parasites that cause a wide spectrum
      of diseases in humans and dogs worldwide. However, monitoring of the Leishmania
      burden in its different hosts is still based on cumbersome and poorly sensitive
      methods. Here we have developed a highly accurate real-time PCR assay with which
      to reproducibly detect and quantify the relative Leishmania major burden in mouse
      tissue samples. The assay is performed with the LightCycler system using SYBR
      Green I and primers amplifying a ca. 120-bp fragment from minicircles of the
      kinetoplast DNA (kDNA). The assay was able to detect as little as 100 fg of L.
      major DNA per reaction, which is equivalent to 0.1 parasite. The standard curve
      designed for quantitation of parasites showed linearity over an at least 6-log
      DNA concentration range, corresponding to 0.1 to 10(4) parasites per reaction,
      with a correlation coefficient of 0.979. The assay also proved to have a
      detection range of the same magnitude as that used for detection of L. donovani
      and L. amazonensis, but it was 100-fold less sensitive for L. mexicana. When
      applied to tissues from experimentally infected mice, the real-time PCR assay is
      not only as sensitive as a conventional PCR assay for detection of Leishmania
      kDNA but also more rapid. Results indicate that this assay is compatible with the
      clinical diagnosis of leishmaniasis and will be a great help to scientists who
      use animals to monitor the efficacy of antileishmanial drugs or vaccines or
      decipher the unique properties of the life cycle of Leishmania spp.

PMID- 11980940
TI  - Testing of susceptibility of Mycobacterium tuberculosis to pyrazinamide with the
      nonradiometric BACTEC MGIT 960 system.
AB  - The reliability of the novel BACTEC MGIT 960 pyrazinamide (PZA) kit (Becton
      Dickinson Microbiology Systems, Sparks, Md.) was assessed for testing of
      susceptibility of Mycobacterium tuberculosis to PZA. Results generated by the
      BACTEC MGIT 960 system (Becton Dickinson) were compared with those obtained with
      the BACTEC 460TB system. Extensive proficiency testing (phase I) and
      reproducibility testing (phase II) as well as susceptibility testing of blinded
      strains of M. tuberculosis from the Centers for Disease Control and Prevention
      (phase III) were performed prior to testing 58 strains isolated from clinical
      specimens (phase IV). After resolution of discrepant results obtained by the two
      BACTEC methods by two other laboratories which acted as independent arbiters
      (phase V), overall agreement of the BACTEC MGIT 960 system with the BACTEC 460TB
      system for PZA testing of phase IV strains was 96.6%. Between the two systems
      there was no statistically significant difference in time until results were
      obtained, i.e., 6.8 days (BACTEC MGIT 960) versus 5.4 days (BACTEC 460TB), the
      latter not counting the time required for a subculture with a growth index of
      200, however. The new BACTEC MGIT PZA susceptibility testing procedure works
      equally well for inocula prepared from liquid (MGIT) and solid (Lowenstein
      Jensen) cultures. PZA MGIT medium in plastic tubes yielded results equivalent to
      medium dispensed in glass tubes.

PMID- 11980941
TI  - Evaluation of the Directigen FluA+B test for rapid diagnosis of influenza virus
      type A and B infections.
AB  - Directigen FluA+B (BD Diagnostic Systems, Sparks, Md.), a new rapid test for the
      detection of influenza virus types A and B, was evaluated with nasopharyngeal
      aspirate specimens collected from 250 patients in comparison with culture and
      direct fluorescent antigen (DFA) detection tests. The patients studied were
      predominantly children, 80% being </=6 years old. Specimens negative by culture
      but positive by the Directigen FluA+B or DFA tests were analyzed by reverse
      transcription-PCR to resolve the discrepant results. The resolved sensitivity,
      specificity, and positive and negative predictive values of the Directigen FluA+B
      test for influenza virus type A were 96%, 99.6%, 96%, and 99.6%, respectively,
      and for influenza virus type B they were 87.5%, 96.8%, 80%, and 98%,
      respectively. Storage of nasopharyngeal aspirates in virus transport medium at 2
      to 8 degrees C for 48 h had little adverse effect on the detection of influenza
      virus type A, but diagnosis of influenza virus type B is best carried out with
      fresh specimens. The test detected a range of human and animal influenza virus A
      subtypes, including the H5N1 and H9N2 viruses that recently caused human disease
      in Hong Kong.

PMID- 11980942
TI  - Evaluation of the VITEK 2 system for identification and antimicrobial
      susceptibility testing of medically relevant gram-positive cocci.
AB  - A study was conducted to evaluate the new VITEK 2 system (bioMerieux) for
      identification and antibiotic susceptibility testing of gram-positive cocci.
      Clinical isolates of Staphylococcus aureus (n = 100), coagulase-negative
      staphylococci (CNS) (n = 100), Enterococcus spp. (n = 89), Streptococcus
      agalactiae (n = 29), and Streptococcus pneumoniae (n = 66) were examined with the
      ID-GPC identification card and with the AST-P515 (for staphylococci), AST-P516
      (for enterococci and S. agalactiae) and AST-P506 (for pneumococci) susceptibility
      cards. The identification comparison methods were the API Staph for staphylococci
      and the API 20 Strep for streptococci and enterococci; for antimicrobial
      susceptibility testing, the agar dilution method according to the procedure of
      the National Committee for Clinical Laboratory Standards (NCCLS) was used. The
      VITEK 2 system correctly identified to the species level (only one choice or
      after simple supplementary tests) 99% of S. aureus, 96.5% of S. agalactiae, 96.9%
      of S. pneumoniae, 92.7% of Enterococcus faecalis, 91.3% of Staphylococcus
      haemolyticus, and 88% of Staphylococcus epidermidis but was least able to
      identify Enterococcus faecium (71.4% correct). More than 90% of gram-positive
      cocci were identified within 3 h. According to the NCCLS breakpoints,
      antimicrobial susceptibility testing with the VITEK 2 system gave 96% correct
      category agreement, 0.82% very major errors, 0.17% major errors, and 2.7% minor
      errors. Antimicrobial susceptibility testing showed category agreement from 94 to
      100% for S. aureus, from 90 to 100% for CNS, from 91 to 100% for enterococci,
      from 96 to 100% for S. agalactiae, and from 91 to 100% for S. pneumoniae.
      Microorganism-antibiotic combinations that gave very major errors were CNS
      erythromycin, CNS-oxacillin, enterococci-teicoplanin, and enterococci-high
      concentration gentamicin. Major errors were observed for CNS-oxacillin and S.
      agalactiae-tetracycline combinations. In conclusion the results of this study
      indicate that the VITEK 2 system represents an accurate and acceptable means for
      performing identification and antibiotic susceptibility tests with medically
      relevant gram-positive cocci.

PMID- 11980943
TI  - Molecular epidemiology of subgroup C avian pneumoviruses isolated in the United
      States and comparison with subgroup a and B viruses.
AB  - The avian pneumovirus (APV) outbreak in the United States is concentrated in the
      north-central region, particularly in Minnesota, where more outbreaks in
      commercial turkeys occur in the spring (April to May) and autumn (October to
      December). Comparison of the nucleotide and amino acid sequences of nucleoprotein
      (N), phosphoprotein (P), matrix (M), fusion (F), and second matrix (M2) genes of
      15 U.S. APV strains isolated between 1996 and 1999 revealed between 89 and 94%
      nucleotide sequence identity and 81 to 95% amino acid sequence identity. In
      contrast, genes from U.S. viruses had 41 to 77% nucleotide sequence identity and
      52 to 78% predicted amino acid sequence identity with European subgroup A or B
      viruses, confirming that U.S. viruses belonged to a separate subgroup. Of the
      five proteins analyzed in U.S. viruses, P was the most variable (81% amino acid
      sequence identity) and N was the most conserved (95% amino acid sequence
      identity). Phylogenetic comparison of subgroups A, B, and C viruses indicated
      that A and B viruses were more closely related to each other than either A or B
      viruses were to C viruses.

PMID- 11980944
TI  - Clinical evaluation of a frozen commercially prepared microdilution panel for
      antifungal susceptibility testing of seven antifungal agents, including the new
      triazoles posaconazole, ravuconazole, and voriconazole.
AB  - A commercially prepared frozen broth microdilution panel (Trek Diagnostic
      Systems, Westlake, Ohio) was compared with a reference microdilution panel for
      antifungal susceptibility testing of two quality control (QC) strains and 99
      clinical isolates of Candida spp. The antifungal agents tested included
      amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole,
      ravuconazole, and voriconazole. Microdilution testing was performed according to
      NCCLS recommendations. MIC endpoints were read visually after 48 h of incubation
      and were assessed independently for each microdilution panel. The MICs for the QC
      strains were within published limits for both the reference and Trek
      microdilution panels. Discrepancies among MIC endpoints of no more than 2
      dilutions were used to calculate the percent agreement. Acceptable levels of
      agreement between the Trek and reference panels were observed for all antifungal
      agents tested against the 99 clinical isolates. The overall agreement for each
      antifungal agent ranged from 96% for ravuconazole to 100% for amphotericin B. The
      Trek microdilution panel appears to be a viable alternative to frozen
      microdilution panels prepared in-house.

PMID- 11980945
TI  - Quantitative microbiological study of human carious dentine by culture and real
      time PCR: association of anaerobes with histopathological changes in chronic
      pulpitis.
AB  - The bacteria found in carious dentine were correlated with the tissue response of
      the dental pulps of 65 teeth extracted from patients with advanced caries and
      pulpitis. Standardized homogenates of carious dentine were plated onto selective
      and nonselective media under anaerobic and microaerophilic conditions. In
      addition, real-time PCR was used to quantify the recovery of anaerobic bacteria.
      Primers and fluorogenic probes were designed to detect the total anaerobic
      microbial load, the genera Prevotella and Fusobacterium, and the species
      Prevotella melaninogenica, Porphyromonas endodontalis, Porphyromonas gingivalis,
      and Micromonas (formerly Peptostreptococcus) micros. The pulpal pathology was
      categorized according to the cellular response and degenerative changes. Analysis
      of cultured bacteria showed a predominance of gram-positive microorganisms,
      particularly lactobacilli. Gram-negative bacteria were also present in
      significant numbers with Prevotella spp., the most numerous anaerobic group
      cultured. Real-time PCR analysis indicated a greater microbial load than that
      determined by colony counting. The total number of anaerobes detected was 41-fold
      greater by real-time PCR than by colony counting, while the numbers of Prevotella
      and Fusobacterium spp. detected were 82- and 2.4-fold greater by real-time PCR
      than by colony counting, respectively. Real-time PCR also identified M. micros,
      P. endodontalis, and P. gingivalis in 71, 60, and 52% of carious samples,
      respectively. Correlation matrices of the real-time PCR data revealed significant
      positive associations between M. micros and P. endodontalis detection and
      inflammatory degeneration of pulpal tissues. These anaerobes have been strongly
      implicated in endodontic infections that occur as sequelae to carious pulpitis.
      Accordingly, the data suggest that the presence of high levels of these bacteria
      in carious lesions may be indicative of irreversible pulpal pathology.

PMID- 11980946
TI  - Calculation of the stability of the IS6110 banding pattern in patients with
      persistent Mycobacterium tuberculosis disease.
AB  - The interpretation of molecular epidemiologic data of Mycobacterium tuberculosis
      infection is dependent on the understanding of the stability and evolutionary
      characteristics of the DNA fingerprinting marker used to classify clinical
      isolates. This study investigated the stability of the IS6110 banding pattern in
      serial tuberculosis isolates collected from patients resident in an area with a
      high incidence of tuberculosis. Evolutionary changes were observed in 4% of the
      strains, and a half-life (t(1/2)) of 8.74 years was calculated, assuming a
      constant rate of change over time. This rate may be composed of a high rate of
      change seen during the early disease phase (t(1/2) = 0.57 years) and a low rate
      of change seen in the late disease phase (t(1/2) = 10.69 years). The early rate
      probably reflects change occurring during active growth prior to therapy, while
      the low late rate may reflect change occurring during or after treatment. We
      demonstrate that the calculation of these rates is strongly influenced by the
      time interval between onset of disease and sputum sampling. These calculations
      are further complicated by partial replacement of the original strain population,
      resulting in the sporadic appearance of clonal variants in sputum specimens.
      Therefore, the true extent of genetic diversity may be underestimated within each
      host, thereby influencing molecular epidemiological data used to establish
      transmission chains.

PMID- 11980947
TI  - Detection, subgroup specificity, and genotype diversity of rotavirus strains in
      children with acute diarrhea in Paraguay.
AB  - Of a total of 220 stool specimens from children with acute diarrhea, mostly under
      the age of 3 years, collected in Paraguay between January 1999 and March 2000, 70
      (31.8%) were found positive for rotaviruses (RV). Positive samples were
      characterized by electropherotyping and subgrouping. Sixty-one (87.1%) were
      classified as group A, subgroup II; one (1.4%) was classified as group A,
      subgroup I; six (8.6%) were group A, non-I non-II; and two (2.9%) were not
      tested. RV strains were G and P genotyped by reverse transcription-PCR. The
      following G types were detected: G4 (34.3%), G1 (21.4%), G2 (1.4%), and G9
      (5.7%). Mixtures of human and animal genotypes were detected in 15 (21.4%)
      samples, and 11 samples (15.7%) were nontypeable. The following P types were
      detected: P[8] (48.6%), P[4] (1.4%), and P[1] (1.4%). A mixed type was found in
      10% of samples, and an unexpectedly high percentage (38.6%) of nontypeable
      samples was found. The common human G- and P-type combinations P[8], G4 (15.7%)
      and P[8], G1 (14.2%) were detected. Mixed human and animal genotypes were
      observed as the following combinations: G4 + G5, G4 + G5 + G10, and G1 + G10 for
      G types and P[8]-P[1] for P types. The emerging G9 genotype was detected in four
      samples. These results show for the first time the diversity of RV circulating
      among children in Paraguay and contribute to the knowledge of this pathogen
      required to devise strategies to prevent diarrheal illness in this country. The
      finding of mixed genotypes may indicate interspecies transmission of RV between
      humans and animals.

PMID- 11980948
TI  - Evaluation of an immunofluorescent-antibody test using monoclonal antibodies
      directed against Enterocytozoon bieneusi and Encephalitozoon intestinalis for
      diagnosis of intestinal microsporidiosis in Bamako (Mali).
AB  - A 2-month study was carried out in Mali to evaluate an immunofluorescent-antibody
      test (IFAT) using monoclonal probes specific for Enterocytozoon bieneusi or
      Encephalitozoon intestinalis. Sixty-one human immunodeficiency virus (HIV)
      seropositive adult patients and 71 immunocompetent children were enrolled.
      Microsporidia were detected in stools from 8 of 61 patients (13.1%) seropositive
      for HIV. A single species, E. bieneusi, was identified. All the children were
      negative for microsporidia. The sensitivity and specificity of IFAT were 100%
      compared with those of PCR, which was used as the "gold standard." Moreover,
      species identification by IFAT was more rapid and less expensive than that by
      PCR. These results show the suitability of IFAT for detection of microsporidia in
      developing countries.

PMID- 11980949
TI  - Real-time LightCycler PCR for detection and discrimination of Bordetella
      pertussis and Bordetella parapertussis.
AB  - Real-time PCR assays based on the LightCycler technology were developed for
      individual (simplex PCR) and simultaneous (duplex PCR) detection and
      discrimination of Bordetella pertussis and Bordetella parapertussis in clinical
      samples. The assays were evaluated with 113 specimens from patients with and
      without symptoms of pertussis. Results were compared to those from conventional
      culture and TaqMan real-time PCR. The analytical sensitivity ranged from 0.1 to
      10 CFU for B. pertussis and B. parapertussis, and intra- and interassay
      variations were less than 7%. Results were available within 2 h. With the simplex
      format, 21 of 100 samples from patients with clinical symptoms of pertussis were
      positive for B. pertussis and/or B. parapertussis. With the duplex format, 18 of
      100 samples were positive. LightCycler PCR increased the diagnostic sensitivity
      over that of culture by 2.0-fold (duplex PCR) (P = 0.08) to 2.3-fold (simplex
      PCR) (P = 0.02). Our data suggest that duplex PCR in this format showed good
      analytical sensitivity but lost some sensitivity on clinical samples compared
      with the simplex format.

PMID- 11980950
TI  - Evaluation of Gen-Probe amplified mycobacterium tuberculosis direct test by using
      respiratory and nonrespiratory specimens in a tertiary care center laboratory.
AB  - The performance of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test
      (Gen-Probe Inc., San Diego, Calif.) was assessed in a large tertiary care
      mycobacteriology laboratory. Both acid-fast smear-positive and smear-negative
      respiratory and nonrespiratory clinical specimens were analyzed. From February
      1998 to 4 October 2001, AMTD assays were performed on 391 respiratory specimens
      and 164 nonrespiratory specimens. The AMTD assay was compared to the "gold
      standard" of combined culture and clinical diagnosis. The overall sensitivity for
      all specimens, including those for which no smear result was available, was
      91.2%. The overall sensitivities of the assay, including acid-fast smear-positive
      and -negative specimens, were 97.8 and 77.3% for respiratory and nonrespiratory
      specimens, respectively. The corresponding specificities for respiratory and
      nonrespiratory specimens were 99.1 and 98.5%, respectively. The overall
      specificity for all specimens was 98.9%. Positive and negative predictive values
      were 93.9 and 99.7% and 91.7 and 96.4% for respiratory and nonrespiratory
      specimens, respectively. The time saved by using the AMTD test for making a
      diagnosis of tuberculosis instead of using culture was 8.99 days. Inhibitors to
      the AMTD assay were found in 3.1% of respiratory specimens and 3.1% of
      nonrespiratory specimens. The assay, used in a general mycobacteriology
      laboratory setting, represents an important advance in improving the speed and
      accuracy of diagnosis in the management of patients with tuberculosis.

PMID- 11980951
TI  - Utility of a multiplex PCR assay for detecting herpesvirus DNA in clinical
      samples.
AB  - A multiplex PCR was designed to amplify herpes simplex virus types 1 and 2,
      cytomegalovirus, and varicella-zoster virus DNA present in a diverse range of
      clinical material. The susceptibility of these viruses to in vivo inhibition by
      at least one antiviral drug was an important consideration in their inclusion in
      the multiplex detection system. An aliquot of equine herpesvirus was introduced
      into each specimen prior to extraction and served as an indicator of potential
      inhibitors of the PCR and a detector of suboptimal PCR conditions. Compared to
      virus isolation and immunofluorescence-based antigen detection, the multiplex
      assay yielded higher detection rates for all viruses represented in the assay.
      The turnaround time for performance of the assay was markedly reduced compared to
      those for the other techniques used to identify these viruses. More than 21,000
      tests have been performed using the assay. Overall, the multiplex PCR enabled the
      detection of substantially increased numbers of herpesviruses, in some cases in
      specimens or anatomical sites where previously they were rarely if ever
      identified using traditional detection methods.

PMID- 11980952
TI  - Comparative analysis of titers of antibody against measles virus in sera of
      vaccinated and naturally infected Japanese individuals of different age groups.
AB  - The anti-measles virus (MV) antibody titers in the sera of vaccinees and
      naturally infected individuals of different age groups were measured to help
      assess the efficacy of the current MV vaccination in Japan. Neutralizing (NT)
      antibody titers induced by vaccination were 2(3.2) times lower than those induced
      by natural infection and declined significantly by age 20. The once-decreased NT
      antibody titers of the vaccinees increased 2(3.6) times during their twenties to
      titers comparable to those of naturally infected individuals of the same age,
      implying the possible occurrence of natural infection in vaccinees with decreased
      anti-MV immunity. Although the current field strains in Japan, types D3 and D5,
      were reported to differ antigenically from each other and from vaccine strains
      (type A) to some extent, as demonstrated by different reactivities to monoclonal
      antibodies, the sera of vaccinees neutralized the two types of field strains and
      the vaccine strain with the same efficiency. This result suggests that the
      current vaccine strain would be suitable to elicit protection against types D3
      and D5, as long as viral antigenicity is concerned. However, when compared at
      given hemagglutination inhibition titers, NT antibody titers of vaccinees were
      2(1.1) to 2(3.2) times lower than those of naturally infected individuals,
      suggesting a qualitative difference(s) of anti-MV antibodies between the two
      groups. It should be emphasized that protective immunity induced by the one-dose
      vaccination currently implemented in Japan may not be strong enough to ensure
      lifelong immunity. A two-dose vaccination program with higher vaccination
      coverage needs to be considered in order to effectively control measles in Japan.

PMID- 11980953
TI  - Rapid identification of Penicillium marneffei by PCR-based detection of specific
      sequences on the rRNA gene.
AB  - An emerging pathogenic dimorphic fungus, Penicillium marneffei, is one of the
      major causes of morbidity in patients with human immunodeficiency virus infection
      in Southeast Asia. A PCR-hybridization assay has been developed to identify this
      pathogen. This study describes the use of single and nested PCR methods for the
      rapid identification of P. marneffei. Two sets of oligonucleotide primers were
      derived from the sequence of 18S rRNA genes of P. marneffei. The outer primers
      (RRF1 and RRH1) were fungus specific. The inner primers (Pm1 and Pm2) were
      specific for P. marneffei and were used in nested or single PCR. The specific
      fragment of approximately 400-bp was amplified from both mold and yeast forms of
      13 P. marneffei human isolates, 12 bamboo rat isolates, and 1 soil isolate, but
      not from other fungi, bacteria, and human DNA. The amplified products were
      analyzed by agarose gel electrophoresis followed by ethidium bromide staining.
      The sensitivities of the single PCR and nested PCR were 1.0 pg/microl and 1.8
      fg/microl, respectively. The assay is useful for rapid identification of P.
      marneffei cultures. Very young culture of P. marneffei (2-day-old filamentous
      colony, 2 mm in diameter) could be performed by this assay. The species was
      identified within 7 h (single PCR) or 10 h (nested PCR), compared to 4 to 7 days
      for confirmation of dimorphism. The application of these PCR methods for early
      diagnosis of the disease needs to be studied further.

PMID- 11980954
TI  - Comparative evaluation of the BD Phoenix and VITEK 2 automated instruments for
      identification of isolates of the Burkholderia cepacia complex.
AB  - We evaluated two new automated identification systems, the BD Phoenix (Becton
      Dickinson) and the VITEK 2 (bioMerieux), for identification of isolates of the
      Burkholderia cepacia complex (BCC). The test sample included 42 isolates of the
      highly virulent and epidemic genomovar III, 45 isolates of B. multivorans, and 47
      isolates of other members of the BCC. Rates of correct identification by the BD
      Phoenix and VITEK 2 were similar when all BCC isolates were considered (50 and
      53%, respectively) but differed markedly for genomovar III (71 and 38%; P < 0.01)
      and for B. multivorans (58 and 89%; P < 0.001). For the BD Phoenix as well as the
      VITEK 2, taking all 134 isolates of the BCC together, rates of correct
      identification of clinical isolates (56 and 55%, respectively; n = 85) were
      higher than those of environmental isolates (21 and 39%, respectively; n = 28).
      Clinical isolates of genomovar III (n = 27) showed correct identification rates
      of 81% (BD Phoenix) and 48% (VITEK 2) (P < 0.01). Rates of misidentification for
      BD Phoenix and VITEK 2 were 9 and 17% for genomovar III, 22 and 7% for B.
      multivorans, and 36 and 13% for the other BCC members (P < 0.01), respectively.
      More than half of the isolates misidentified by each instrument were identified
      as Ralstonia pickettii, Ralstonia paucula (CDC IV C-2 group), Alcaligenes
      faecalis, Achromobacter spp., or, for the VITEK 2, "various nonfermenters." This
      study reemphasizes that confirmatory identification of BCC, preferably by
      molecular methods, is highly recommended.

PMID- 11980955
TI  - PreservCyt transport medium used for the ThinPrep Pap test is a suitable medium
      for detection of Chlamydia trachomatis by the COBAS Amplicor CT/NG test: results
      of a preliminary study and future implications.
AB  - The commercial COBAS Amplicor CT/NG test (Roche Diagnostic Systems, Meylan,
      France) is a sensitive and specific method for detection of Chlamydia trachomatis
      infections. This test currently consists of using a nucleic acid amplification
      method to detect C. trachomatis in first-void urine specimens and in endocervical
      swabs collected in 2-sucrose-phosphate (2SP) transport medium. We conducted a
      prospective study to determine whether the automated COBAS Amplicor CT/NG test
      can detect C. trachomatis in cervical specimens collected in PreservCyt transport
      medium (ThinPrep Pap Test; Cytyc Corporation, Boxborough, Mass.). PreservCyt
      medium is used to preserve cervical samples before the preparation of ThinPrep
      slides. We collected 1,000 cervical specimens from young women (age range, 15 to
      25 years) during routine Pap smear tests. Only specimens with normal cytology and
      in which the gynecologist found no clinical evidence of urogenital infections
      were selected. The samples were stored in PreservCyt transport medium at 15 to 20
      degrees C. C. trachomatis was detected in 22 of the 1,000 cervical specimens that
      had been stored in PreservCyt. To confirm the positive samples, the test was
      repeated on new endocervical swab specimens collected in 2SP transport medium.
      Only 9 of the 22 positive patients agreed to undergo this control, but all 9
      retested positive. To evaluate the influence of storage conditions on the
      sensitivity of the C. trachomatis PCR test, all of the positive samples were
      stored at 15 to 20 degrees C in PreservCyt transport medium and were retested
      every 2 weeks for 6 weeks. C. trachomatis was successfully amplified from all 22
      specimens for the whole 6-week period. The prevalence of C. trachomatis infection
      was 2.2% in our study population. These results demonstrate that PreservCyt
      transport medium is a suitable transport medium for detection of C. trachomatis
      by the COBAS Amplicor CT/NG test. The ThinPrep Pap Test may enable gynecologists
      to monitor for both cervical lesions and C. trachomatis infections with a single
      endocervical specimen.

PMID- 11980956
TI  - Enhanced enzyme-linked immunosorbent assay for detection of antibodies to virus
      like particles of human papillomavirus.
AB  - Measurement of antibodies to human papillomavirus (HPV) is complicated by many
      factors. Although enzyme-linked immunosorbent assays (ELISAs) that use virus-like
      particles (VLPs) have proved useful, the assays have, in general, had moderate
      sensitivities and low signal-to-noise ratios. To enhance the performance of the
      assay, a systematic investigation was undertaken to examine key variables used in
      ELISAs for the detection of antibodies to VLPs of HPV. Incorporation of two vinyl
      polymers, polyvinyl alcohol (molecular weight, 50,000) (PVA-50) and
      polyvinylpyrrolidone (molecular weight, 360,000) (PVP-360), was found to increase
      the sensitivity as well as the specificity of the assay for the detection of
      antibodies to VLPs of HPV. In particular, the addition of PVA-50 to the blocking
      solution reduced the amount of nonspecific binding of antibodies to VLPs and the
      microplate surface, whereas the addition of PVP-360 increased the sensitivity of
      antibody detection. The new ELISA demonstrated increased sensitivity and
      specificity for the detection of cervical HPV type 16 infection compared to those
      of a prototype assay with coded clinical serum samples from women with known
      cervicovaginal HPV infection status. It is anticipated that the enhanced ELISA
      conditions will have wide application to a large number of clinical diagnostic
      assays.

PMID- 11980957
TI  - Significant closure of the human immunodeficiency virus type 1 and hepatitis C
      virus preseroconversion detection windows with a transcription-mediated
      amplification-driven assay.
AB  - While the present generation of serology-based assays has significantly decreased
      the number of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus
      (HCV) infections acquired by transfusion, the possibility of infected donations
      escaping detection still exists. The average seronegative viremic window duration
      during which immunological assays are unable to detect the virus is estimated to
      be between 16 and 22 days for HIV-1 and approximately 70 days for HCV.
      Significant reduction of detection window duration was demonstrated using a
      nucleic acid amplification assay, the Procleix HIV-1/HCV Assay, which utilizes
      transcription-mediated amplification technology to simultaneously detect HIV-1
      and HCV RNAs. For 26 commercially available HIV-1 seroconversion panels tested,
      specimens were reactive in the HIV-1/HCV assay at the same time as or earlier
      than in serological assays. Overall, the HIV-1/HCV assay was able to reduce the
      detection window duration by an average of 14 days and 6 days compared to tests
      relying on recognition of HIV-1 antibody and p24 antigen, respectively. For 24
      commercially available HCV seroconversion panels tested, the specimens were
      reactive in the HIV-1/HCV assay at an earlier blood sampling date than in
      serological assays, reducing the detection window duration by an average of 26
      days. Similar results were obtained in testing the HIV-1 and HCV seroconversion
      panels in the virus-specific HIV-1- and HCV-discriminatory assays, respectively.
      In conclusion, the HIV-1/HCV assay and corresponding discriminatory assays
      significantly reduced detection window durations compared to immunoassays.

PMID- 11980958
TI  - Real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid
      samples from mothers with primary infection.
AB  - A real-time PCR assay was developed to quantify human cytomegalovirus (HCMV) DNA
      in amniotic fluid (AF) samples collected from 30 pregnant women with primary HCMV
      infection as detected either from HCMV-immunoglobulin G (IgG) seroconversion or
      by the presence of HCMV-specific IgG and IgM associated with a low IgG avidity.
      Clinical information available for each case included ultrasonographic
      examination and fetal or newborn outcome. HCMV infection of fetuses or newborns
      was confirmed for the 30 studied cases. AF samples were subdivided into three
      groups. In group A (n = 13), fetuses presented major ultrasound abnormalities,
      and pregnancy was terminated. In group B (n = 13), fetuses had normal ultrasound
      findings, the pregnancy went to term, and the newborns were asymptomatic at
      birth. In group C (n = 4), fetuses had no or minor ultrasonographic signs, and
      pregnancy was terminated. The HCMV DNA load values in AF samples were
      significantly higher in group A (median, 2.8 x 10(5) genome equivalents [GE]/ml)
      than in group B (median, 8 x 10(3) GE/ml) (P = 0.014). Our findings suggest that
      HCMV load level in AF samples correlates with fetal clinical outcome but might
      also be dependent on other factors, such as the gestational age at the time of AF
      sampling and the time elapsed since maternal infection.

PMID- 11980960
TI  - Application of the C(18)-carboxypropylbetaine specimen processing method to
      recovery of Mycobacterium avium subsp. paratuberculosis from ruminant tissue
      specimens.
AB  - The causative agent of Johne's disease is Mycobacterium avium subsp.
      paratuberculosis. This is a chronic, debilitating gastrointestinal disorder that
      affects ruminants and is responsible for significant economic loss. The specimen
      processing method that combines C(18)-carboxypropylbetaine (CB-18) treatment and
      lytic enzyme decontamination has been shown to improve the diagnosis of
      mycobacterioses. This processing method was applied to the isolation of M. avium
      subsp. paratuberculosis from ruminant tissue samples. The BACTEC 12B liquid
      culture system was used but was supplemented with 1% egg yolk emulsion, 4 microg
      of mycobactin J, and 0.5% pyruvate (12B/EMP) for use in conjunction with this
      method. The final concentration of antibiotics used was 10 microg of vancomycin,
      30 microg of amphotericin B, and 20 microg of nalidixic acid (VAN) per ml. A 7H10
      based solid medium was also used that included mycobactin J, pyruvate, and VAN
      but excluded the egg yolk emulsion (7H10/MPV). Several M. avium subsp.
      paratuberculosis isolates were examined during the evaluation of this processing
      method. It was observed that treatment with lytic enzymes stimulated the growth
      of M. avium subsp. paratuberculosis; however, the growth of one isolate was
      markedly inhibited due to the presence of vancomycin. Subsequently, the
      vancomycin concentration in the VAN formulation was reduced to 2 microg/ml. A
      blinded panel of 60 previously characterized tissue samples from bovine and bison
      were then processed and analyzed by smear and culture. Historically, 31 and 37
      specimens were classified as positive by histology and culture, respectively. The
      overall sensitivity and specificity of smear relative to culture following CB-18
      processing were 97.6 and 89.5%, respectively. The 12B/EMP/VAN liquid culture
      system recovered M. avium subsp. paratuberculosis from 39 specimens, whereas
      7H10/MPV and Herrold's egg yolk media recovered M. avium subsp. paratuberculosis
      from 26 and 16 specimens, respectively. The average times to positive were 7.4 +/
      8.3, 29.9 +/- 2.6, and 24 +/- 0 days, respectively. The contamination rates were
      4.8, 22.6, and 20.0%, respectively.

PMID- 11980959
TI  - Shiga toxin-producing Escherichia coli infection and antibodies against Stx2 and
      Stx1 in household contacts of children with enteropathic hemolytic-uremic
      syndrome.
AB  - Ninety-five household contacts (aged 2 months to 73 years) of patients with
      enteropathic hemolytic-uremic syndrome (HUS) were investigated for the presence
      of immunoglobulin (Ig) G antibodies to Shiga toxins Stx2 and Stx1 by Western blot
      assay. Thirty-one percent of the household contacts and 19% of 327 controls had
      anti-Stx2 IgG (heavy and light chain [H + L]), 5 and 8%, respectively, had anti
      Stx1 IgG (H + L), and 3 and 2%, respectively, had both anti-Stx2 and anti-Stx1
      IgG (H + L). The incidence of infections with Stx-producing Escherichia coli
      (STEC) was determined based on the following diagnostic criteria: STEC isolation,
      detection of stx gene sequences, free fecal Stx in stool filtrates, and serum IgM
      antibodies against E. coli O157 lipopolysaccharide. Evidence of STEC infection
      was observed in 25 household contacts, of whom 18 (72%) were asymptomatic and
      represented a potential source of infection. Six of 13 (46%) household contacts
      with Stx2-producing E. coli O157:H7 in stool culture developed anti-Stx2 IgG (H +
      L), compared to 71% of Stx2-associated HUS cases. In individuals showing anti
      Stx2 IgG (H + L), the antibody response was directed against the B subunit in 69%
      of household contacts and 71% of controls, in contrast to 28% of HUS patients. In
      this investigation controls had a significant increase of the median of IgM
      antibodies to O157 lipopolysaccharide (LPS) with age, up to the fifth decade. The
      lack of disease in household contacts with B subunit-specific antibodies, as well
      as the significantly higher median of anti-O157 LPS IgM antibodies in controls
      beyond 4.9 years of age, suggests a protective role for anti-Stx and anti-O157
      LPS antibodies.

PMID- 11980961
TI  - Development and application of a new scheme for typing Campylobacter jejuni and
      Campylobacter coli by PCR-based restriction fragment length polymorphism
      analysis.
AB  - A molecular typing approach for Campylobacter jejuni and Campylobacter coli was
      developed with restriction fragment length polymorphism analysis of a 9.6-kb PCR
      amplified portion of the lipopolysaccharide gene cluster. Sixty-one Penner
      serotype reference strains were analyzed with this new genotyping scheme, and 32
      genogroups were found. Eleven additional genogroups were obtained from 87
      clinical C. jejuni strains tested. This molecular typing method shows a
      correlation with the Penner heat-stable serotyping method, a phenotypic typing
      method based on lipopolysaccharide structures that is often used as a "gold
      standard" for subtyping Campylobacter spp. This strong correlation suggests that
      the data obtained can be directly compared with epidemiological data collected in
      the past by classical serotyping of C. jejuni and C. coli. In contrast to the
      high percentage of nontypeability by phenotyping, this molecular typing method
      results in 100% typeability and provides a superior alternative to serotyping.

PMID- 11980962
TI  - Molecular characterization of pigmented and nonpigmented isolates of
      Mycobacterium avium subsp. paratuberculosis.
AB  - Five pigmented isolates of Mycobacterium avium subsp. paratuberculosis were
      examined by pulsed-field gel electrophoresis (PFGE), IS900 restriction fragment
      length polymorphism (IS900-RFLP), and IS1311 polymorphism analysis using PCR. All
      of the pigmented isolates exhibited one of three distinct PFGE profiles with
      SnaBI, designated 9, 10, and 11, and with SpeI, designated 7, 8, and 9, which
      generated three multiplex profiles designated [9-7], [10-8], and [11-9]. All of
      the pigmented isolates had the same IS900-RFLP BstEII and PvuII profiles. The
      IS900-RFLP BstEII profile was new, but the IS900-RFLP PvuII profile corresponded
      to PvuII type 6 of a sheep strain described by Cousins and colleagues (D. V.
      Cousins, S. N. Williams, A. Hope, and G. J. Eamens, Aust. Vet. J. 78:184-190,
      2000). IS1311-PCR analysis typed all of the pigmented isolates as sheep (S)
      strains. The genetic relationship between pigmented and nonpigmented isolates was
      investigated by using multiplex PFGE data from the analysis of both the 5
      pigmented isolates and 88 nonpigmented isolates of M. avium subsp.
      paratuberculosis from a variety of host species and geographic locations. It was
      possible to classify the isolates into two distinct types designated type I,
      comprising the pigmented isolates, and type II, comprising the nonpigmented
      isolates, which exhibit a very broad host range.

PMID- 11980964
TI  - Correlation between the elastase activity index and invasiveness of clinical
      isolates of Aspergillus fumigatus.
AB  - We calculated an elastase activity index (EAI) by dividing the diameter of the
      elastin lysis halo by the fungal growth diameter. After 10 days' incubation at 37
      degrees C, all strains but one obtained from invasive aspergillosis showed an EAI
      > or = 1. Of the 18 strains obtained from colonized patients, only 4 (22.2%) had
      an EAI > or = 1, whereas neither of the strains isolated from patients with
      fungus ball reached this value. Overall, 44 out of the 142 strains obtained from
      the environment had an EAI > or = 1 (30.9%).

PMID- 11980963
TI  - Molecular analysis of group A Streptococcus type emm18 isolates temporally
      associated with acute rheumatic fever outbreaks in Salt Lake City, Utah.
AB  - Acute rheumatic fever (ARF) and subsequent rheumatic heart disease are rare but
      serious sequelae of group A Streptococcus (GAS) infections in most western
      countries. Salt Lake City (SLC), Utah, and the surrounding intermountain region
      experienced a resurgence of ARF in 1985 which has persisted. The largest numbers
      of cases were encountered in 1985-1986 and in 1997-1998. Organisms with a mucoid
      colony phenotype when grown on blood agar plates were temporally associated with
      the higher incidence of ARF. To develop an understanding of the molecular
      population genetic structure of GAS strains associated with ARF in the SLC
      region, 964 mucoid and nonmucoid pharyngeal isolates recovered in SLC from 1984
      to 1999 were studied by sequencing the emm gene. Isolates with an emm18 allele
      were further characterized by sequencing the spa, covR, and covS genes. Peak
      periods of ARF were associated with GAS isolates possessing an emm18 allele
      encoding the protein found in serotype M18 isolates. Among the serotype M18
      isolates, the difference in the number of C repeats produced three size variants.
      Variation was limited in spa, a gene that encodes a streptococcal protective
      antigen, and covR and covS, genes that encode a two-component regulatory system
      that, when inactivated, results in a mucoid phenotype and enhanced virulence in
      mouse infection models. Pulsed-field gel electrophoresis showed a single
      restriction profile for serotype M18 organisms isolated during both peak periods
      of ARF. In SLC, the incidence of ARF coresurged with the occurrence of GAS
      serotype M18 isolates that have very restricted genetic variation.

PMID- 11980965
TI  - Recovery of an unusual fusogenic herpes simplex virus type 2 strain from a
      clinical specimen.
AB  - A highly unusual herpes simplex virus type 2 strain, strain Burr, was isolated
      from a female genital tract clinical specimen. This virus induced remarkably
      rapid and extensive syncytium formation in Vero cells involving hundreds of cells
      but was less fusion active in HEp-2 cells, MRC-5 cells, and mink lung cells.
      Virus-infected cells produced the glycoproteins gB, gC, gD and gE.

PMID- 11980966
TI  - Performance characteristics of VIDAS and directigen respiratory syncytial virus
      (RSV) antigen detection assays and culture for the identification of RSV in
      respiratory specimens.
AB  - In a comparison of the Directigen and VIDAS respiratory syncytial virus antigen
      detection assays with viral culture, the sensitivity, specificity, positive and
      negative predictive values, and testing efficiency were 86, 93.1, 82.7, 94.6, and
      91.2% for Directigen; 96.1, 90.8, 80.3, 98.3, and 92.3% for VIDAS; and 88.2, 100,
      100, 95.7, and 96.8% for viral culture, respectively.

PMID- 11980967
TI  - Rapid PCR-based identification of methicillin-resistant Staphylococcus aureus
      from screening swabs.
AB  - A PCR identification of methicillin-resistant Staphylococcus aureus (MRSA),
      obviating the need for subculture on agar media, was investigated. The
      combination of MRSA detection by mecA femB PCR with prior enrichment in selective
      broth was tested for 439 swabs. PCR identified 36 MRSA-positive samples, in
      concordance with conventional methods.

PMID- 11980968
TI  - Molecular identification of Staphylococcus lugdunensis in a patient with
      meningitis.
AB  - A 12-year-old child developed meningitis 6 days after a third ventriculostomy by
      endoscopy. A coagulase-negative Staphylococcus sp. was isolated in pure culture
      from the cerebrospinal fluid and was definitely identified as Staphylococcus
      lugdunensis after the 16S ribosomal DNA gene and rpoB gene were sequenced. This
      report describes the first case of S. lugdunensis meningitis.

PMID- 11980969
TI  - Sequence analysis of the ribosomal DNA intergenic spacer 1 regions of
      Trichosporon species.
AB  - We determined the sequence of the intergenic spacer (IGS) 1 region, which is
      located between the 26S and 5S rRNA genes, in 25 species of the genus
      TRICHOSPORON: IGS 1 sequences varied in length from 195 to 719 bp. Comparative
      sequence analysis suggested that the divergence of IGS 1 sequences has been
      greater than that of the internal transcribed spacer regions. We also identified
      five genotypes of T. asahii, which is a major causative agent of deep-seated
      trichosporonosis, based on the IGS 1 sequences of 43 strains. Most of the
      isolates that originated in Japan were of genotype 1, whereas the American
      isolates were of genotype 3 or 5. Our results suggest that analysis of IGS
      regions provides a powerful method to distinguish between phylogenetically
      closely related species and that a geographic substructure may exist among T.
      asahii clinical isolates.

PMID- 11980970
TI  - In vitro activities of terbinafine in combination with fluconazole, itraconazole,
      voriconazole, and posaconazole against clinical isolates of Candida glabrata with
      decreased susceptibility to azoles.
AB  - A checkerboard microdilution method, performed according to the recommendations
      of the National Committee for Clinical Laboratory Standards, was used to study
      the in vitro interaction of terbinafine (TRB) with fluconazole (FLU),
      itraconazole (ITRA), voriconazole (VRC), and posaconazole (PSZ) in 24 isolates of
      Candida glabrata with decreased susceptibility to azoles isolated from the oral
      cavities of human immunodeficiency virus patients. Synergy, defined as a
      fractional inhibitory concentration index of < or =0.5, was observed in 17% of
      TRB-FLU interactions, 21% of TRB-ITRA interactions, 33% of TRB-VRC interactions,
      and 12% of TRB-PSZ interactions. Where synergy was not achieved, there was still
      a decrease in the MIC of one or both drugs when used in combination. Antagonism
      was not observed in any drug combination. Clinical studies are warranted to
      elucidate the potential utility of these combination therapies.

PMID- 11980971
TI  - Invasive meningococcal disease in Scotland, 1994 to 1999, with emphasis on group
      B meningococcal disease.
AB  - A review was carried out on 774 invasive meningococcal isolates reported to the
      active meningococcal surveillance system in Scotland from 1994 to 1999. This
      showed that serogroups B (51.7%) and C (39.2%) caused the majority of disease.
      The six common PorB proteins (4, 1, 15, 2B, 12, and 21) and PorA proteins
      (serosubtypes) (P1.4, P1.15, P1.9, P1.14, P1.7, and P1.16) accounted for 50 and
      51% of all group B isolates, respectively, during the study period.

PMID- 11980972
TI  - Comparison of chromogenic and fluorogenic membrane filtration methods for
      detection of four Candida species.
AB  - CHROMagar Candida medium was inoculated with a variety of clinical samples (n =
      282) by using membrane filtration instead of swabbing or streaking. This modified
      CHROMagar procedure increased the ability to detect yeast by 16.7%. Compared to
      an enzymatic two-step membrane filtration method with fluorogenic substrates, it
      yielded similar recovery but was slower.

PMID- 11980973
TI  - Potential application of nonstructural protein NS1 serotype-specific
      immunoglobulin G enzyme-linked immunosorbent assay in the seroepidemiologic study
      of dengue virus infection: correlation of results with those of the plaque
      reduction neutralization test.
AB  - An NS1 serotype-specific indirect enzyme-linked immunosorbent assay (ELISA) was
      developed to differentiate primary and secondary dengue virus infections and
      serotypes of primary dengue virus infection. For this report, we carried out
      retrospective seroepidemiologic studies on serum samples collected from residents
      of Liuchiu Hsiang, Pingtung County, an isolated island in southern Taiwan during
      1997-1998. The results demonstrated that good correlation existed between dengue
      virus NS1 serotype-specific immunoglobulin G (IgG) ELISA and dengue virus plaque
      reduction neutralization test (PRNT). Our data suggested that NS1 serotype
      specific IgG ELISA could replace PRNT for seroepidemiologic studies to
      differentiate Japanese encephalitis and dengue virus infections and for dengue
      virus serotyping.

PMID- 11980974
TI  - Molecular diagnosis of Granulicatella elegans on the cardiac valve of a patient
      with culture-negative endocarditis.
AB  - We herein report one case of culture-negative infectious endocarditis (IE) where
      the organism, Granulicatella elegans, was identified by molecular analysis using
      broad-range PCR primers complementary to the 16S rRNA gene on the removed valve.
      The results and utility of this method are discussed.

PMID- 11980975
TI  - Detection of porcine circovirus types 1 and 2 in serum and tissue samples of pigs
      with and without postweaning multisystemic wasting syndrome.
AB  - Presence of porcine circovirus type 1 (PCV1) and PCV2 was studied in sera and
      superficial inguinal lymph nodes from postweaning multisystemic wasting syndrome
      (PMWS)-affected and non-PMWS-affected pigs by using in situ hybridization and
      PCR. PCV1 and PCV2 were found in less than 3% and more than 50% of the samples,
      respectively. The most sensitive technique and site was PCR in superficial
      inguinal lymph nodes, but in situ hybridization correlated better with presence
      of characteristic lesions.

PMID- 11980976
TI  - Household transmission of Streptococcus pneumoniae among siblings with acute
      otitis media.
AB  - Nasopharyngeal transmission of Streptococcus pneumoniae was evaluated among 23
      siblings with acute otitis media (AOM). Restriction fragment length polymorphism
      revealed that the nasopharyngeal strains were identical between siblings in 12 of
      13 clusters of AOM experienced in 11 families. This study demonstrated person-to
      person transmission of S. pneumoniae, especially drug-resistant strains, among
      siblings with AOM.

PMID- 11980977
TI  - Microsatellite characterization of Plasmodium falciparum from cerebral and
      uncomplicated malaria patients in southern Vietnam.
AB  - If parasite genotype influences the clinical course of malaria, we expect that
      isolates from patients with similar pathology would be more closely related than
      would be expected by chance. To explore this prediction, we typed nine
      microsatellite markers in sympatric Plasmodium falciparum isolates from cerebral
      and uncomplicated malaria patients from Vietnam. Temporal structure and linkage
      disequilibrium were also examined in this data set.

PMID- 11980978
TI  - Comparison of an automated ribotyping system to restriction endonuclease analysis
      and pulsed-field gel electrophoresis for differentiating vancomycin-resistant
      Enterococcus faecium isolates.
AB  - The RiboPrinter Microbial Characterization System was compared with pulsed-field
      gel electrophoresis (PFGE), restriction endonuclease analysis (REA), and
      epidemiological data for typing 45 vancomycin-resistant Enterococcus faecium
      (VRE) isolates. In 21 clinically related isolates, 90 to 100% were similar by
      PFGE and REA, but only 57% were similar by the RiboPrinter. In another eight
      clinically related isolates, three isolates similar by PFGE and REA were all
      unique by the RiboPrinter. In contrast, in 16 clinically unrelated isolates, the
      predominant RiboPrinter ribotype represented 50% of the strains, while the
      largest PFGE and REA clones represented less than 19% of the strains. These data
      suggest that the RiboPrinter is not reliable for VRE investigation.

PMID- 11980979
TI  - Pneumocystis carinii f. sp. hominis is not infectious for SCID mice.
AB  - The infectious power of Pneumocystis carinii f. sp. hominis was explored by
      inoculating SCID mice intranasally with either P. carinii f. sp. hominis or P.
      carinii f. sp. muris isolates. Only mice inoculated with mouse parasites
      developed Pneumocystis pneumonia, as assessed by microscopy and PCR. These
      results suggest that humans do not contract pneumocystosis from animals.

PMID- 11980980
TI  - Epidemiological dynamics of hepatitis C virus among 747 German individuals: new
      subtypes on the advance.
AB  - This study demonstrates the dynamics in the epidemiology of hepatitis C virus
      subtypes. Subtypes 3a and 4a have become increasingly prevalent in patients where
      an infection within recent years can be assumed. Evidence is presented that the
      subtypes observed among younger patients can spread rapidly and lead to
      significant changes in the subtype distribution.

PMID- 11980981
TI  - Evidence of the presence of IS1245 and IS1311 or closely related insertion
      elements in nontuberculous mycobacteria outside of the Mycobacterium avium
      complex.
AB  - A PCR assay based on the simultaneous detection of IS1245 and IS1311 was
      developed and used to determine the host range of these insertion elements.
      Specific PCR products were observed in Mycobacterium malmoense, Mycobacterium
      scrofulaceum, and Mycobacterium nonchromogenicum, indicating that IS1245 and
      IS1311 are not limited to the Mycobacterium avium complex.

PMID- 11980982
TI  - Tetrazolium microplate assay as a rapid and inexpensive colorimetric method for
      determination of antibiotic susceptibility of Mycobacterium tuberculosis.
AB  - The emergence of multidrug-resistant tuberculosis underscores the need for low
      cost, rapid methods to determine the susceptibility of Mycobacterium tuberculosis
      to antibiotics. A new, rapid, easily read, and inexpensive colorimetric method
      with a tetrazolium indicator performs this determination as quickly and
      accurately as the more expensive Alamar Blue technique.

PMID- 11980983
TI  - Diversity of rotavirus strains among children with acute diarrhea in China: 1998
      2000 surveillance study.
AB  - As part of a national rotavirus surveillance activity, we collected fecal
      specimens from 3,177 children with acute diarrhea in 10 regions of China between
      April 1998 and April 2000 and screened them for rotavirus. Rotavirus was detected
      in 41% (n = 1,305) of specimens, and in these, G1 was the predominant serotype
      (72.6%), followed by G3 (14.2%), G2 (12.1%), G4 (2.5%), G9 (0.9%), and G
      untypeable (0.7%). Among 327 G-typed strains tested for P genotype, 14 different
      P-G combinations were identified, with the globally common strains P[8]G1,
      P[4]G2, P[8]G3, and P[8]G4 representing 75.6% of all typed rotavirus strains.
      Among the uncommon strains, 11 were P[6]G9, and others included P[6]G1, P[6]G3,
      and five novel P-G combinations (P[9]G1, P[4]G1, P[4]G3, P[4]G4, and P[8]G2). Our
      results indicate that while the common rotavirus strains remain predominant, the
      diversity of strains is much greater than was previously recognized.

PMID- 11980984
TI  - Candida glabrata oropharyngeal candidiasis in patients receiving radiation
      treatment for head and neck cancer.
AB  - Candida glabrata colonization is common in patients receiving radiation treatment
      for head and neck cancer, but to our knowledge has never been described as the
      infecting organism with oropharyngeal candidiasis (OPC). This study presents the
      first three patients described with C. glabrata OPC in this patient population.
      Patient 1 developed C. glabrata OPC and required fluconazole, 800 mg/day, for
      clinical resolution. Antifungal susceptibility testing revealed a MIC of
      fluconazole of >64 microg/ml. Elapsed time from initial culturing to treatment
      decision was 7 days. Patients 2 and 3 developed C. glabrata OPC. They were
      patients in a study evaluating OPC infections, and cultures were taken
      immediately. CHROMagar Candida plates with 0, 8, and 16 microg of fluconazole/ml
      were employed for these cultures. Lavender colonies, consistent with C. glabrata,
      grew on the 0- and 8-microg plates but not on the 16-microg plate from patient 2
      and grew on all three plates from patient 3. Based on these data, a fluconazole
      dose of 200 mg/day was chosen for patient 2 and a dose of 400 mg/day was chosen
      for patient 3, with clinical resolution in both. Elapsed time from initial
      culturing to treatment decision was 2 days. C. glabrata does cause OPC in head
      and neck radiation treatment patients, and the use of fluconazole-impregnated
      chromogenic agar may significantly reduce treatment decision time compared to
      that with conventional culturing and antifungal susceptibility testing.

PMID- 11980985
TI  - False-negative results in typing of group B streptococci by the standard
      lancefield antigen extraction method.

PMID- 11980986
TI  - Molecular epidemiology of Stenotrophomonas maltophilia isolated from cystic
      fibrosis patients.

PMID- 11980989
TI  - Beyond the development of quality-of-life instruments: where do we go from here?

PMID- 11980990
TI  - Targeting the epidermal growth factor receptor with tyrosine kinase inhibitors:
      small molecules, big hopes.

PMID- 11980991
TI  - Shedding old paradigms: developing viruses to treat cancer.

PMID- 11980992
TI  - Low-grade gliomas: answering one question in a myriad of new questions.

PMID- 11980993
TI  - Reducing treatment-related morbidity and mortality in early-stage Hodgkin's
      disease and why the recent Southwest Oncology Group Trial is not the way to go.

PMID- 11980994
TI  - Measuring health-related quality of life in patients with hepatobiliary cancers:
      the functional assessment of cancer therapy-hepatobiliary questionnaire.
AB  - PURPOSE: This is the first report on the development and initial validation of
      the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep)
      questionnaire, a 45-item self-report instrument designed to measure health
      related quality of life (HRQL) in patients with hepatobiliary cancers. The FACT
      Hep consists of the 27-item FACT-G, which assesses generic HRQL concerns, and the
      newly validated 18-item Hepatobiliary Subscale (HS), which assesses disease
      specific issues. PATIENTS AND METHODS: The development of the HS followed a four
      phase process of item generation, item reduction, scale construction, and
      reliability/validity testing. Two independent samples were studied: item
      generation (sample 1; n = 30) and reliability/validity testing (sample 2; n =
      51). RESULTS: In sample 2, all subscales and aggregated scores showed high
      internal consistency at initial assessment (Cronbach's alpha range, 0.72 to 0.94)
      and retesting (Cronbach's alpha range, 0.81 to 0.94). Measurement stability over
      a 3- to 7-day period was also high for all aggregated scales (test-retest
      correlation range, 0.84 to 0.91; intraclass correlation coefficient range, 0.82
      to 0.90). Convergent and divergent validity were demonstrated by examining
      relationships between FACT subscales and mood, social support, and social
      desirability. Finally, when performance status and treatment status were used to
      divide sample 2, the HS differentiated groups to a degree comparable to the
      Physical and Functional Well-Being subscales of the FACT-G, thereby contributing
      favorably to a 32-item Trial Outcome Index. In addition to the 18 validated,
      scored items in the HS, seven treatment-related items may be appended, if
      clinically indicated, as a separate subscale. CONCLUSION: The 45-item FACT-Hep
      can be used independently as a brief measure of disease-related symptoms and
      functioning. Alone or paired with the FACT-G, the HS has promise for use in
      assessing the disease-specific HRQL of patients with hepatobiliary cancers.

PMID- 11980995
TI  - ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase
      inhibitor, is well tolerated and active in patients with solid, malignant tumors:
      results of a phase I trial.
AB  - PURPOSE: To investigate the tolerability, pharmacokinetics, and antitumor
      activity of the oral, selective epidermal growth factor receptor-tyrosine kinase
      inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS:
      This was an open, phase I, escalating multiple-dose tolerability and
      pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days
      followed by 14 days off treatment. Dose escalation started at 50 mg/d and
      continued to 925 mg or until consistent dose-limiting toxicity (DLT) was
      observed. RESULTS: Sixty-four patients were entered at eight dose levels. The
      most frequent dose-related grade 1 and 2 adverse events were an acne-like (or
      folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700
      mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were
      uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half
      life was 48 hours (range, 37 to 65). Four of 16 patients with non-small-cell lung
      cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700
      mg/d. Overall, 16 patients remained on study for > or = 3 months, with seven of
      these patients (five with NSCLC, including three of the patients with partial
      response) remaining on study for > or = 6 months. CONCLUSION: ZD1839 was well
      tolerated, with DLT observed at a dose well above that at which antitumor
      activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable
      for administration as a once-daily oral tablet formulation. Phase II monotherapy
      and phase III combination trials in NSCLC are being conducted to investigate
      further the efficacy, tolerability, and optimal daily dose of ZD1839.

PMID- 11980996
TI  - Phase I trial of intravenous administration of PV701, an oncolytic virus, in
      patients with advanced solid cancers.
AB  - PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes
      regression of tumor xenografts after intravenous administration. This phase I
      study was designed to define the maximum-tolerated dose (MTD) and safety of
      single and multiple intravenous doses of PV701 as a single agent in patients with
      cancer. PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers
      that were unresponsive to standard therapy were enrolled. Four PV701 intravenous
      dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2)
      repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower
      dose followed by two higher doses in 1 week every 28 days; and (4) two week: one
      lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS: A
      100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of
      12 x 10(9) plaque-forming units (PFU)/m(2) was established for outpatient dosing.
      After an initial dose of 12 x 10(9) PFU/m(2), patients tolerated an MTD for
      subsequent doses of 120 x 10(9) PFU/m(2). The most common adverse events were flu
      like symptoms that occurred principally after the first dose and were decreased
      in number and severity with each subsequent dose. Tumor site-specific adverse
      events and acute dosing reactions were also observed but not cumulative toxicity.
      Objective responses occurred at higher dose levels, and progression-free survival
      ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11
      months of therapy and showed evidence of PV701 particles budding from the tumor
      cell membrane by electron microscopy and a pronounced lymphoplasmacytic
      infiltrate by histologic examination. CONCLUSION: PV701 warrants further study as
      a novel therapeutic agent for cancer patients.

PMID- 11980997
TI  - Prospective randomized trial of low- versus high-dose radiation therapy in adults
      with supratentorial low-grade glioma: initial report of a North Central Cancer
      Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology
      Group study.
AB  - PURPOSE: To compare survival and toxicity in adult patients treated with low-dose
      (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized
      radiation therapy (RT) for supratentorial low-grade astrocytoma,
      oligodendroglioma, and mixed oligoastrocytoma. PATIENTS AND METHODS: From 1986 to
      1994, 203 eligible/analyzable patients were randomized: 101 to low-dose RT, 102
      to high-dose RT. Almost half were younger than 40 years, and 95% had grade 2
      tumors. Histologic subtype was astrocytoma (or mixed oligo-astrocytoma with
      astrocytoma dominant) in 32% of patients and oligodendroglioma (or
      oligoastrocytoma with oligodendroglioma dominant) in 68%. Tumor diameter was less
      than 5 cm in 35% of patients, and 41% of tumors showed some degree of contrast
      enhancement. Extent of resection was gross total in 14% of patients, subtotal in
      35%, and biopsy only in 51%. RESULTS: At the time of the present analysis, 83
      patients (41%) are dead, and median follow-up is 6.43 years in the 120 who are
      still alive. Survival at 2 and 5 years is nonsignificantly better with low-dose
      RT; survival at 2 and 5 years was 94% and 72%, respectively, with low-dose RT and
      85% and 64%, respectively, with high-dose RT (log rank P =.48). Multivariate
      analysis identified histologic subtype, tumor size, and age as the most
      significant prognostic factors. Survival is significantly better in patients who
      are younger than 40 years and in patients who have oligodendroglioma or oligo
      dominant histology. Grade 3 to 5 radiation neurotoxicity (necrosis) was observed
      in seven patients, with one fatality in each treatment arm. The 2-year actuarial
      incidence of grade 3 to 5 radiation necrosis was 2.5% with low-dose RT and 5%
      with high-dose RT. CONCLUSION: This phase III prospective randomized trial of low
      versus high-dose radiation therapy for adults with supratentorial low-grade
      astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower
      survival and slightly higher incidence of radiation necrosis in the high-dose RT
      arm. The most important prognostic factors for survival are histologic subtype,
      tumor size, and age. The study design of the ongoing intergroup trial in this
      population will be discussed.

PMID- 11980998
TI  - Phase II trial of carmustine plus O(6)-benzylguanine for patients with
      nitrosourea-resistant recurrent or progressive malignant glioma.
AB  - PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)
      alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to
      define the activity and toxicity of this regimen in the treatment of adults with
      progressive or recurrent malignant glioma resistant to nitrosoureas. PATIENTS AND
      METHODS: Patients were treated with O(6)-BG at an intravenous dose of 120 mg/m(2)
      followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week
      intervals. RESULTS: Eighteen patients were treated (15 with glioblastoma
      multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None
      of the 18 patients demonstrated a partial or complete response. Two patients
      exhibited stable disease for 12 weeks before their tumors progressed. Three
      patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing
      therapy because of hematopoietic toxicity. Twelve patients experienced reversible
      > or = grade 3 hematopoietic toxicity. There was no difference in half-lives
      (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/-
      1.7 microg/mL/h v 5.0 +/- 1.3 microg/mL/h) of O(6)-BG for patients receiving
      phenytoin and those not treated with this drug. CONCLUSION: These results
      indicate that O(6)-BG plus BCNU at the dose schedule used in this trial is
      unsuccessful in producing tumor regression in patients with nitrosourea-resistant
      malignant glioma, although stable disease was seen in five patients for 6, 12,
      12, 12, and 18 weeks. Future use of this approach will require strategies to
      minimize dose-limiting toxicity of BCNU such as regional delivery or
      hematopoietic stem-cell protection.

PMID- 11980999
TI  - Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and
      stem-cell rescue: results of the Chicago Pilot II Study.
AB  - PURPOSE: To investigate whether intensive induction therapy followed by triple
      tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue and
      local irradiation will improve event-free survival for patients with high-risk
      neuroblastoma. PATIENTS AND METHODS: From August 1995 to January 2000, 25
      consecutive newly diagnosed high-risk neuroblastoma patients and one child with
      recurrent MYCN-amplified disease were enrolled onto the Chicago Pilot II
      Protocol. After induction therapy and surgery, peripheral-blood stem cells were
      mobilized with three cycles of high-dose cyclophosphamide and granulocyte colony
      stimulating factor. Patients then underwent triple-tandem cycles of high-dose
      therapy with peripheral-blood stem-cell rescue followed by radiation to the
      primary site. RESULTS: Twenty-two of the 26 patients successfully completed
      induction therapy and were eligible for the triple-tandem consolidation high-dose
      therapy. Sufficient numbers of peripheral-blood stem cells were collected in all
      but one patient. Seventeen patients were able to complete all three cycles of
      high-dose therapy and peripheral-blood stem-cell rescue, two patients completed
      two cycles, and three patients completed one cycle. There was one toxic death,
      and one patient died from complications of treatment for graft failure. With a
      median follow-up of 38 months, the 3-year event-free survival and survival rates
      are 57% +/- 11% and 79% +/- 10%, respectively. CONCLUSION: The results of this
      pilot study demonstrate that it is feasible to intensify consolidation with
      triple-tandem high-dose chemotherapy and peripheral-blood stem-cell rescue and
      local irradiation, and suggest that this treatment strategy may lead to improved
      survival for patients with high-risk neuroblastoma.

PMID- 11981000
TI  - Non-Hodgkin's lymphoma arising in bone in children and adolescents is associated
      with an excellent outcome: a Children's Cancer Group report.
AB  - PURPOSE: Non-Hodgkin's lymphoma (NHL) arising in bone is a heterogeneous
      histologic type of NHL that includes large-cell lymphoma, lymphoblastic lymphoma,
      and small noncleaved-cell lymphoma. NHL arising in bone is well recognized in
      adults but is less well characterized and infrequent in children and adolescents.
      PATIENTS AND METHODS: We performed a retrospective review of Children's Cancer
      Group (CCG) studies treating children and adolescents with NHL over a 20-year
      period (CCG-551, CCG-501, CCG-502, CCG-503, CCG-552, CCG-5911, and CCG-5941) and
      determined the response and event-free survival (EFS) rates in 31 patients with
      NHL arising in bone. RESULTS: The patients ranged in age from 3 to 17 years
      (median, 11 years; mean, 11 years), and 64.5% were male. All 31 (100%) patients
      achieved complete response. For 31 patients with NHL arising in bone, the product
      limit estimated 5-year EFS was 83.8% +/- 6.7%. EFS in 17 patients with localized
      disease (Murphy stages I and II) was 94.1% +/- 5.7%, and EFS in 14 patients with
      disseminated disease (Murphy stage III) was 70.7% +/- 12.4% (log-rank P =.10).
      EFS in 17 patients treated with chemotherapy and radiation was 70.1% +/- 11.2%,
      and EFS in 14 patients treated with chemotherapy without radiation was 100% (P
      =.03). EFS in 26 patients with histology-directed treatment (LSA2-L2 or ADCOMP
      for lymphoblastic, other therapy for nonlymphoblastic) was 92.2% +/- 5.3%, and in
      five patients with nonhistology-directed treatment it was 40.0% +/- 21.9% (P
      <.001). CONCLUSION: NHL arising in bone is a heterogeneous type of NHL that makes
      up approximately 2.0% of NHL in children and adolescents on CCG studies. Response
      and survival in this young age group seem superb, with histology-directed
      treatment protocols without radiation in both localized and disseminated disease.

PMID- 11981001
TI  - Favorable impact of the t(9;11) in childhood acute myeloid leukemia.
AB  - PURPOSE: To determine the impact of MLL rearrangements on the outcome of children
      with acute myeloid leukemia (AML). PATIENTS AND METHODS: We analyzed the clinical
      and biologic features of 298 infants and children with primary AML treated on
      four consecutive institutional clinical trials. The Kaplan-Meier method was used
      in survival analysis and the Cox proportional-hazards model was used to analyze
      the effect of potential prognostic factors on event-free survival (+/- 1 SE).
      RESULTS: Molecular studies of 152 cases detected 42 with MLL rearrangements. The
      karyotypes of these 42 revealed the t(9;11) (15 cases), abnormalities of
      chromosomes 10 and 11 (nine cases), the t(11;19) (four cases), other
      abnormalities of 11q23 (seven cases), and miscellaneous rearrangements (seven
      cases). Among these 42 patients, the 15 whose leukemic cells carried the t(9;11)
      had a better outcome (66% +/- 15%) than the other 27 (25.9% +/- 11.2%; P =.004).
      Cases with the t(9;11) were also characterized by M5 AML morphology (21 of 23
      cases). Of the 63 patients with M5 AML, the 21 whose leukemic cells demonstrated
      the t(9;11) had a better outcome (71.1% +/- 11%) than the other 42 (25.8% +/-
      7.9%; P =.0004). The only independent factors indicating a favorable prognosis
      were presenting leukocyte count less than 50 x 10(9)/L (relative risk of relapse,
      0.73; 95% confidence interval, 0.55 to 0.97; P =.03) and the t(9;11) (relative
      risk of relapse, 0.32; 95% confidence interval, 0.16 to 0.64; P =.002).
      CONCLUSION: We conclude that the t(9;11) is the most favorable genetic factor for
      patients with AML treated at our institution.

PMID- 11981002
TI  - The pathology of familial breast cancer: predictive value of immunohistochemical
      markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with
      mutations in BRCA1 and BRCA2.
AB  - PURPOSE: The morphologic and molecular phenotype of breast cancers may help
      identify patients who are likely to carry germline mutations in BRCA1 and BRCA2.
      This study evaluates the immunohistochemical profiles of tumors arising in
      patients with mutations in these genes. MATERIALS AND METHODS: Samples of breast
      cancers obtained from the International Breast Cancer Linkage Consortium were
      characterized morphologically and immunohistochemically using antibodies to
      estrogen receptor, progesterone receptor, HER-2 (c-erbB-2 oncogene), and p53
      protein. RESULTS: Breast cancers in patients with BRCA1 germline mutations are
      more often negative for estrogen receptor, progesterone receptor, and HER-2, and
      are more likely to be positive for p53 protein compared with controls. In
      contrast, BRCA2 tumors do not show a significant difference in the expression of
      any of these proteins compared with controls. CONCLUSION: BRCA1 has a distinctive
      morphology and immunohistochemical phenotype. The combined morphologic and
      immunohistochemical data can be used to predict the risk of a young patient
      harboring a germline mutation in BRCA1. The BRCA2 phenotype is currently not well
      defined.

PMID- 11981003
TI  - Assessment of molecular markers of clinical sensitivity to single-agent taxane
      therapy for metastatic breast cancer.
AB  - PURPOSE: The taxanes affect tubulin polymerization and interfere with mitotic
      transition. A checkpoint blockade at the G(1)-S boundary would be expected to
      promote taxane-induced apoptotic cell death through a mechanism that may involve
      p27. Other proposed determinants of clinical taxane sensitivity/resistance
      include p53, members of the epidermal growth factor receptor (EGFR) superfamily
      (e.g., HER2, EGFR), and estrogen receptors and progesterone receptors. These
      molecular markers and their correlation with clinical taxane sensitivity are
      investigated in this retrospective clinicopathologic study. PATIENTS AND METHODS:
      We performed immunohistochemistry (IHC) for estrogen receptors, progesterone
      receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients
      treated for metastatic breast cancer on a series of clinical trials of single
      agent taxane chemotherapy for correlation with clinical response (complete or
      partial response). Patient characteristics that could influence response (i.e.,
      performance status, extent of disease, and prior therapy) were also examined.
      RESULTS: In univariate analysis, Karnofsky performance status > or = 90% and no
      prior history of anthracycline therapy correlated with a good clinical response
      to single-agent taxane (P =.003 and P =.041, respectively). None of the IHC
      variables tested were predictive of clinical response to taxane therapy, although
      p27 negativity showed a trend toward significance (P =.075). Concordance between
      the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the
      monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943);
      however, neither univariate nor multivariate analysis demonstrated an association
      between HER2 status and response to taxane chemotherapy. CONCLUSION: The IHC
      biomarkers studied were not predictive of response to single-agent taxane
      chemotherapy in patients with metastatic breast cancer. Identification of
      molecular correlates of taxane response remains an important goal.

PMID- 11981004
TI  - Treatment of Waldenstrom's macroglobulinemia with rituximab.
AB  - PURPOSE: Waldenstrom's macroglobulinemia (WM) is a low-grade lymphoplasmacytic
      lymphoma in which CD20 is usually expressed on tumor cells. There is evidence
      that patients with WM may benefit from treatment with the anti-CD20 monoclonal
      antibody rituximab. We performed a prospective phase II study to clearly define
      the activity of rituximab in patients with this disease. PATIENTS AND METHODS:
      Twenty-seven patients with WM were treated with rituximab 375 mg/m(2)
      intravenously (IV) for 4 weeks. Three months after completion of rituximab,
      patients without evidence of progressive disease received repeat 4-week courses
      of this agent. All patients were symptomatic, their median age was 72 years, and
      15 patients were previously untreated. RESULTS: Twelve patients (44%; 95%
      confidence interval, 25.5% to 64.7%) achieved a partial response after treatment
      with rituximab. Median time to response was 3.3 months (range, 2.2 to 7.1
      months). Responses occurred in six (40%) of 15 previously untreated patients and
      in six (50%) of 12 pretreated patients. Patients with a serum immunoglobulin M
      less than 40 g/L had a significantly higher response rate. The median time to
      progression for all patients was 16 months, and with a median follow-up of 15.7
      months, nine of 12 responding patients remain free of progression. Treatment with
      rituximab was well tolerated, with approximately one fourth of patients
      experiencing some mild form of infusion-related toxicity, usually fever and
      chills. CONCLUSION: Our prospective data indicate that rituximab is well
      tolerated and active in patients with WM. Previously untreated and pretreated
      patients seem to benefit equally. Repeat 4-week courses of rituximab may prolong
      the duration of response of the disease, but this observation requires
      confirmation in prospective, randomized trials. Furthermore, studies that will
      combine rituximab with chemotherapy may be relevant.

PMID- 11981005
TI  - Long-term medical outcomes and quality-of-life assessment of patients with
      chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow
      transplantation.
AB  - PURPOSE: Benchmark analysis of patients with chronic myeloid leukemia (CML) alive
      for more than 10 years after allogeneic bone marrow transplantation (BMT)
      including data on disease status, bone marrow reserve, long-term complications,
      and quality of life (QOL). PATIENTS AND METHODS: Eighty-nine patients (46 in
      first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML
      during the study period. Medical outcomes and QOL of patients were analyzed
      retrospectively. RESULTS: Twenty-eight (31.5%) of 89 patients were alive at 10
      years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors
      never relapsed. Fifteen patients relapsed between 0.5 and 16 years after
      transplantation. Ten patients showed a hematologic relapse and received salvage
      treatment. Five patients showed transient low levels of BCR-ABL-positive cells by
      Southern blot with no subsequent hematologic relapse. One of the 28 patients died
      in blast crisis at 12 years. The most frequent long-term complications were
      chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of
      clonogenic progenitors remained persistently decreased. QOL assessment yielded
      lower scores in physical performance as compared with an age-matched normative
      population, whereas social functioning was equivalent. A high degree of
      satisfaction was noted with interpersonal relationships. CONCLUSION: Patients
      with CML surviving their BMT long term do well in terms of medical outcomes. A
      constant rate of relapse was noted, with a high salvage rate of affected
      patients, suggesting the need for lifelong monitoring. QOL is perceived as good,
      particularly as related to social functioning; however, it is inferior to a
      normative population with regard to physical performance.

PMID- 11981006
TI  - Autologous transplantation for aggressive non-Hodgkin's lymphoma: results of a
      randomized trial evaluating graft source and minimal residual disease.
AB  - PURPOSE: To determine whether the source of autologous hematopoietic stem cells
      altered the clinical outcomes of patients undergoing high-dose chemotherapy and
      hematopoietic stem-cell transplantation (HSCT) for aggressive non-Hodgkin's
      lymphoma (NHL). PATIENTS AND METHODS: Of 105 high-risk, persistent, or relapsed
      NHL patients slated for an autologous HSCT entered onto this trial, 93 eligible
      patients were randomized to receive cytokine-naive autologous bone marrow
      transplantation (ABMT) (n = 46) or mobilized peripheral-blood stem-cell
      transplantation (PBSCT) (n = 47). All patients received carmustine, etoposide,
      cytarabine, and cyclophosphamide as the conditioning regimen. PBSCT patients also
      received identical mobilization with granulocyte colony-stimulating factor (G
      CSF) 10 microg/kg/d, and both groups received G-CSF 5 microg/kg/d after the
      infusion of the stem-cell product until neutrophil engraftment. RESULTS: PBSCT
      patients had significantly faster engraftment of all cell lineages: median time
      to absolute neutrophil count > or = 500/microL, 10 days versus 13 days on the
      ABMT arm; median time to platelet count greater than 20,000/microL untransfused,
      11 days versus 15 days on the ABMT arm; and median time to RBC transfusion
      independence, 8 days versus 16 days on the ABMT arm. The complete response rate
      was 72% for PBSCT and 54% for ABMT. The death rate before posttransplant day 100
      was 2% on the ABMT arm and 6% on PBSCT arm. Event-free survival was 37% for PBSCT
      and 37% for ABMT. However, overall survival for PBSCT was 61% compared with 43%
      for ABMT. CONCLUSION: Patients with aggressive NHL receiving HSCT randomized to
      PBSCT demonstrated improved neutrophil engraftment and platelet and RBC
      transfusion independence. The complete response rate and EFS were not
      statistically different by randomization arm. Patients whose harvests were
      positive for minimal residual disease by molecular analysis had poorer EFS.

PMID- 11981007
TI  - Effects of long-term intravenous ibandronate therapy on skeletal-related events,
      survival, and bone resorption markers in patients with advanced multiple myeloma.
AB  - PURPOSE: Bisphosphonates have been found to reduce the incidence of skeletal
      related events (SREs) in patients with multiple myeloma. This is the first double
      blind, randomized, placebo-controlled study to assess the efficacy of
      ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in
      advanced-stage multiple myeloma patients. PATIENTS AND METHODS: Patients with
      multiple myeloma stage II or III were randomly assigned to receive either
      ibandronate 2 mg or placebo as a monthly intravenous (IV) bolus injection for 12
      to 24 months in addition to conventional chemotherapy. SREs such as peripheral
      pathologic or vertebral fractures, hypercalcemia, severe bone pain, and bone
      radiotherapy or surgery were analyzed. Bone-turnover markers were also studied.
      Finally, post hoc analyses of bone morbidity and survival were performed.
      RESULTS: Ninety-nine patients per treatment group were assessable for efficacy
      analysis. The occurrence of SRE per patient year and the time to first SRE were
      not significantly different between the two treatment groups. In overall
      evaluation, no differences were found between the treatment groups regarding bone
      pain, analgesic drug use, quality of life, and median survival (33.1 v 28.2
      months, respectively). Explorative post hoc analyses revealed that ibandronate
      patients with strongly suppressed bone-turnover markers (> or = 30% and > or =
      50% mean reduction of serum osteocalcin and urinary C-terminal telopeptides)
      developed significantly less bone morbidity. Ibandronate was tolerated well
      during as many as 25 therapy cycles. CONCLUSION: Monthly injections of
      ibandronate 2 mg IV neither reduced bone morbidity nor prolonged survival in the
      overall population of stage II/III multiple myeloma patients.

PMID- 11981008
TI  - Phase II trial of the pegylated liposomal doxorubicin in previously treated
      metastatic endometrial cancer: a Gynecologic Oncology Group study.
AB  - PURPOSE: To determine whether pegylated liposomal doxorubicin (PLD) has antitumor
      activity in pretreated patients with persistent or recurrent endometrial
      carcinoma and to define the nature and degree of toxicity of PLD. PATIENTS AND
      METHODS: Women with histologically documented recurrent or persistent measurable
      endometrial carcinoma and with failure of one prior treatment regardless of prior
      anthracycline therapy were enrolled. PLD was administered intravenously over a 1
      hour period at a dose of 50 mg/m(2) every 4 weeks; the dosage was modified in
      accordance with observed toxicity. RESULTS: Of 46 patients entered, 42 were
      assessable for response, as three were declared ineligible on central pathology
      review and one was not assessable for response. Forty had received prior
      chemotherapy, 11 hormonal therapy, and 29 radiation therapy. Doxorubicin had been
      given to 32 patients, carboplatin with paclitaxel to six, carboplatin to one, and
      fluorouracil to one. Four patients had partial responses lasting 1.1, 2.1, 3.3,
      and 5.4 months; the overall response rate was 9.5% (95% confidence interval, 2.7%
      to 22.6%). Three of these responses (in liver and in lymph node) occurred in
      patients who had progressed after doxorubicin with either paclitaxel or
      cisplatin. The median number of courses was 2.5 (range, one to 14). Toxicity was
      generally mild: only 25 patients experienced leukopenia, with a median WBC count
      of 2,900 (range, 800 to 3,900) at nadir. The only grade 4 toxicities were one
      episode each of esophagitis, hematuria, and vomiting. The median overall survival
      was 8.2 months. CONCLUSION: PLD has only limited activity in pretreated advanced,
      recurrent endometrial cancer, but further trials in anthracycline-naive patients
      and in previously untreated patients are ongoing. Its toxicity profile should
      permit its use in combination with myelosuppressive drugs.

PMID- 11981009
TI  - Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel
      refractory ovarian cancer.
AB  - PURPOSE: We wished to critically examine the level of activity of weekly
      paclitaxel in a patient population with well-characterized platinum/paclitaxel
      resistant (3-week schedule) ovarian cancer. PATIENTS AND METHODS: Eligibility
      criteria for this phase II trial included the following: ovarian and fallopian
      tube cancers or primary carcinoma of the peritoneum; prior initial therapy with
      platinum/paclitaxel; and failure to respond to treatment (progression or stable
      disease as best response), or a response duration of less than 3 months, or if
      the response was more than 3 months, retreatment with both agents required and
      failure to respond a second time or the response duration was less than 3 months.
      Measurable or assessable disease (CA-125 response criteria) was required.
      Patients received weekly paclitaxel (80 mg/m(2)) until disease progression,
      unacceptable toxicity developed, or they elected to discontinue treatment.
      RESULTS: Fifty-three patients (52 assessable for toxicity and 51 for response)
      were entered onto this multi-institution trial. Of 248 total cycles (887 doses),
      only 13 (1%) were modified (dose reduction or treatment delay) because of side
      effects. Therapy was discontinued in five patients because of toxicity (four
      because of peripheral neuropathy, and one because of painful fingernail beds).
      Thirteen patients (25%; 95% confidence interval, 13.5% to 37.5%) achieved an
      objective response (four by CA-125 criteria, and nine by > or = 50% reduction of
      measurable disease). CONCLUSION: Weekly paclitaxel (80 mg/m(2)) is generally well
      tolerated and is an active second-line regimen against ovarian cancer that has
      demonstrated resistance to platinum/paclitaxel delivered on an every-3-week
      schedule.

PMID- 11981010
TI  - Temporal change in risk of metachronous contralateral renal cell carcinoma:
      influence of tumor characteristics and demographic factors.
AB  - PURPOSE: To determine the relative risk (RR) of developing a metachronous
      contralateral renal tumor after an initial diagnosis of renal cell carcinoma
      (RCC), with stratification by renal tumor characteristics, demographic factors,
      and follow-up duration, in order to develop an improved risk-based surveillance
      strategy. PATIENTS AND METHODS: The 1973 to 1997 Surveillance, Epidemiology, and
      End Results database was used to determine the observed and expected number of
      metachronous contralateral renal tumors developing after an initial diagnosis of
      RCC. RESULTS: A total of 43,483 patients had a first diagnosis of RCC.
      Contralateral RCC developed subsequently in 155 (0.4%) of 40,049 patients with
      follow-up who had no synchronous diagnosis of RCC, with 10.81 expected cases (RR,
      14.3; 95% CI, 12.2 to 16.8). The respective RRs (and 95% CIs) for contralateral
      RCC for white men and women were 16.0 (11.1 to 22.3) and 13.7 (7.7 to 22.6) at
      less than 2 years, 8.8 (5.0 to 14.3) and 10.5 (5.0 to 19.3) at 2 to 5 years, 13.5
      (8.1 to 21.0) and 5.1 (1.4 to 13.2) at 5 to 10 years, and 13.0 (6.2 to 23.9) and
      13.7 (5.0 to 29.9) at > or = 10 years, respectively. The RRs were significantly
      higher in black compared with white men for the first 5 years, with the RRs (and
      95% CIs) in the former group of 95.3 (58.2 to 146.7) at less than 2 years and
      41.9 (16.8 to 86.3) at 2 to 5 years. CONCLUSION: The incidence of metachronous
      contralateral RCC is stable on long-term follow-up, suggesting that surveillance
      of the contralateral kidney should remain rigorous on extended follow-up. Black
      men are at a significantly higher risk of developing contralateral RCC in the
      first 5 years of follow-up.

PMID- 11981011
TI  - Treatment outcome and survival associated with metastatic renal cell carcinoma of
      non-clear-cell histology.
AB  - PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma
      (RCC) with histology other than clear-cell type, including collecting duct (or
      medullary carcinoma), papillary, chromophobe, and unclassified histologies.
      PATIENTS AND METHODS: Sixty-four patients with metastatic non-clear-cell RCC
      histology were the subjects of this retrospective review. Included in the
      analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of
      1,166 patients from a surgery database, and 23 of 357 patients from a pathology
      database. RESULTS: The prevalent histology was collecting duct, present in 26
      (41%) patients. The number of patients with chromophobe and papillary histologies
      was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors
      that could not be classified for specific tumor histology. Among the 43 patients
      treated with 86 systemic therapies, including 37 cytokine therapies, two patients
      (5%) were observed to have a partial response. The median overall survival time
      was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer
      for patients with chromophobe tumors compared with collecting duct or papillary
      histology, and this group included four patients with survival of greater than 3
      years. CONCLUSION: RCC consists of a heterogeneous group of tumors including
      clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types.
      Non-clear-cell histologies constitute less than 10% of patients in general
      populations of patients with advanced RCC treated on clinical trials. Metastatic
      non-clear-cell RCC is characterized by a resistance to systemic therapy and poor
      survival, with the survival for patients with chromophobe tumors longer than that
      for patients with metastatic collecting duct or papillary RCC. Treatment with
      novel agents on clinical trials is warranted.

PMID- 11981012
TI  - Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a
      result of multiple myeloma.
AB  - PURPOSE: We prospectively evaluated the safety and efficacy of kyphoplasty in the
      treatment of osteolytic vertebral compression fractures resulting from multiple
      myeloma. The principle symptoms in multiple myeloma result from bone destruction,
      especially the spine. Kyphoplasty is a new technique that involves the
      introduction of inflatable bone tamps (IBT) into the vertebral body. The purpose
      of the IBT is to restore the vertebral body back toward its original height,
      while creating a cavity that can be filled with highly viscous bone cement.
      PATIENTS AND METHODS: Fifty-five consecutive kyphoplasty procedures were
      performed in 18 patients with osteolytic vertebral compression fractures
      resulting from multiple myeloma. Cement leakage and any complications were
      recorded. Early objective analysis was made by comparing preoperative and latest
      Short Form 36 Health Survey scores. Height restoration was estimated by measuring
      vertebral height on lateral radiographs. RESULTS: The mean age of patients was
      63.5 years, mean duration of symptoms was 11 months, and mean follow-up was 7.4
      months. There were no major complications related directly to use of this
      technique. On average, 34% of height lost at the time of fracture was restored.
      Asymptomatic cement leakage occurred at two (4%) of 55 levels. Significant
      improvement in SF36 scores occurred for Bodily Pain (23.2 to 55.4, P =.0008),
      Physical Function (21.3 to 50.6, P =.0010), Vitality (31.3 to 47.5, P =.010), and
      Social Functioning (40.6 to 64.8, P =.014). CONCLUSION: Kyphoplasty was
      efficacious in the treatment of osteolytic vertebral compression fractures
      resulting from multiple myeloma. Kyphoplasty is associated with early clinical
      improvement of pain and function as well as some restoration of vertebral body
      height.

PMID- 11981013
TI  - Clinical relevance of MGMT in the treatment of cancer.
AB  - Anumber of DNA-damaging chemotherapeutic agents attack the O(6) position on
      guanine, forming the most potent cytotoxic DNA adducts known. The DNA repair
      enzyme O(6)-alkylguanine DNA alkyltransferase (AGT), encoded by the gene MGMT,
      repairs alkylation at this site and is responsible for protecting both tumor and
      normal cells from these agents. Cells and tissues vary greatly in AGT expression,
      not only between tissues but also between individuals. AGT activity correlates
      inversely with sensitivity to agents that form O(6)-alkylguanine DNA adducts,
      such as carmustine (BCNU), temozolomide, streptozotocin, and dacarbazine. The one
      exception is those tumors lacking mismatch repair, which renders them resistant
      to methylating agents. A recent study in patients with gliomas confirmed the
      correlation between low-level expression of the MGMT gene and response and
      survival after BCNU. An inhibitor to AGT, O(6)-benzylguanine (BG), depletes AGT
      in human tumors without associated toxicity and is now in phase II clinical
      trials. Finally, mutations within the active site region of the MGMT gene render
      the AGT protein resistant to BG inactivation. As a result, mutant MGMT gene
      transfer into hematopoietic stem cells has been shown to selectively protect the
      marrow from the combination of an alkylating agent and BG, while at the same time
      sensitizing tumor cells. MGMT remains a paradigm for development of new agents
      that modulate known mechanisms of drug resistance in cancer cells and raise the
      spectra of combinatorial therapies that encompass known drug resistance
      mechanisms.

PMID- 11981014
TI  - Unusual presentations of uncommon tumors: case 1. Benign metastasizing
      pleomorphic adenoma.

PMID- 11981015
TI  - Unusual presentations of uncommon tumors: case 2. Gastric carcinoid metastatic to
      the liver.

PMID- 11981016
TI  - Unusual presentations of uncommon tumors: case 3. Giant cell plasmacytoma
      presenting as an intraperitoneal mass.

PMID- 11981017
TI  - An existential oncologist.

PMID- 11981018
TI  - Opioid rotation to methadone: proceed with caution.

PMID- 11981019
TI  - Inhibition of opioid analgesia by selective serotonin reuptake inhibitors.

PMID- 11981020
TI  - Cation-selective mutations in the M2 domain of the inhibitory glycine receptor
      channel reveal determinants of ion-charge selectivity.
AB  - Ligand-gated ion channel receptors mediate neuronal inhibition or excitation
      depending on their ion charge selectivity. An investigation into the determinants
      of ion charge selectivity of the anion-selective alpha1 homomeric glycine
      receptor (alpha1 glycine receptor [GlyR]) was undertaken using point mutations to
      residues lining the extra- and intracellular ends of the ion channel. Five mutant
      GlyRs were studied. A single substitution at the intracellular mouth of the
      channel (A-1'E GlyR) was sufficient to convert the channels to select cations
      over anions with P(Cl)/P(Na) = 0.34. This result delimits the selectivity filter
      and provides evidence that electrostatic interactions between permeating ions and
      pore residues are a critical factor in ion charge selectivity. The P-2'Delta
      mutant GlyR retained its anion selectivity (P(Cl)/P(Na) = 3.81), but it was much
      reduced compared with the wild-type (WT) GlyR (P(Cl)/P(Na) = 27.9). When the A
      1'E and the P-2'Delta mutations were combined (selectivity double mutant [SDM]
      GlyR), the relative cation permeability was enhanced (P(Cl)/P(Na) = 0.13). The
      SDM GlyR was also Ca(2+) permeable (P(Ca)/P(Na) = 0.29). Neutralizing the
      extracellular mouth of the SDM GlyR ion channel (SDM+R19'A GlyR) produced a more
      Ca(2+)-permeable channel (P(Ca)/P(Na) = 0.73), without drastically altering
      monovalent charge selectivity (P(Cl)/P(Na) = 0.23). The SDM+R19'E GlyR, which
      introduces a negatively charged ring at the extracellular mouth of the channel,
      further enhanced Ca(2+) permeability (P(Ca)/P(Na) = 0.92), with little effect on
      monovalent selectivity (P(Cl)/P(Na) = 0.19). Estimates of the minimum pore
      diameter of the A-1'E, SDM, SDM+R19'A, and SDM+R19'E GlyRs revealed that these
      pores are larger than the alpha1 GlyR, with the SDM-based GlyRs being comparable
      in diameter to the cation-selective nicotinic acetylcholine receptors. This
      result provides evidence that the diameter of the ion channel is also an
      important factor in ion charge selectivity.

PMID- 11981021
TI  - Single channel analysis of conductance and rectification in cation-selective,
      mutant glycine receptor channels.
AB  - Members of the ligand-gated ion channel superfamily mediate fast synaptic
      transmission in the nervous system. In this study, we investigate the molecular
      determinants and mechanisms of ion permeation and ion charge selectivity in this
      family of channels by characterizing the single channel conductance and
      rectification of alpha1 homomeric human glycine receptor channels (GlyRs)
      containing pore mutations that impart cation selectivity. The A-1'E mutant GlyR
      and the selectivity double mutant ([SDM], A-1'E, P-2' Delta) GlyR, had mean
      inward chord conductances (at -60 mV) of 7 pS and mean outward conductances of 11
      and 12 pS (60 mV), respectively. This indicates that the mutations have not
      simply reduced anion permeability, but have replaced the previous anion
      conductance with a cation one. An additional mutation to neutralize the ring of
      positive charge at the extracellular mouth of the channel (SDM+R19'A GlyR) made
      the conductance-voltage relationship linear (14 pS at both 60 and -60 mV). When
      this external charged ring was made negative (SDM+R19'E GlyR), the inward
      conductance was further increased (to 22 pS) and now became sensitive to external
      divalent cations (being 32 pS in their absence). The effects of the mutations to
      the external ring of charge on conductance and rectification could be fit to a
      model where only the main external energy barrier height for permeation was
      changed. Mean outward conductances in the SDM+R19'A and SDM+R19'E GlyRs were
      increased when internal divalent cations were absent, consistent with the
      intracellular end of the pore being flanked by fixed negative charges. This
      supports our hypothesis that the ion charge selectivity mutations have inverted
      the electrostatic profile of the pore by introducing a negatively charged ring at
      the putative selectivity filter. These results also further confirm the role of
      external pore vestibule electrostatics in determining the conductance and
      rectification properties of the ligand-gated ion channels.

PMID- 11981022
TI  - Effects of aldosterone on biosynthesis, traffic, and functional expression of
      epithelial sodium channels in A6 cells.
AB  - The collecting duct regulates Na(+) transport by adjusting the abundance/activity
      of epithelial Na(+) channels (ENaC). In this study we have investigated the
      synthesis, degradation, endocytosis, and activity of ENaC and the effects of
      aldosterone on these processes using endogenous channels expressed in the A6 cell
      line. Biochemical studies were performed with a newly raised set of specific
      antibodies against each of the three subunits of the amphibian ENaC. Our results
      indicate simultaneous transcription and translation of alpha, beta, and gamma
      subunits and enhancement of both processes by aldosterone: two- and fourfold
      increase, respectively. The biosynthesis of new channels can be followed by
      acquisition of endoglycosidase H-resistant oligosacharides in alpha and beta
      subunits and, in the case of alpha, by the appearance of a form resistant to
      reducing agents. The half-life of the total pool of subunits (t(1/2) 40-70 min)
      is longer than the fraction of channels in the apical membrane (t(1/2) 12-17
      min). Aldosterone induces a fourfold increase in the abundance of the three
      subunits in the apical membrane without significant changes in the open
      probability, kinetics of single channels, or in the rate of degradation of ENaC
      subunits. Accordingly, the aldosterone response could be accounted by an increase
      in the abundance of apical channels due, at least in part, to de novo synthesis
      of subunits.

PMID- 11981023
TI  - Openings of the rat recombinant alpha 1 homomeric glycine receptor as a function
      of the number of agonist molecules bound.
AB  - The functional properties of rat homomeric alpha 1 glycine receptors were
      investigated using whole-cell and outside-out recording from human embryonic
      kidney cells transfected with rat alpha1 subunit cDNA. Whole-cell dose-response
      curves gave EC(50) estimates between 30 and 120 microM and a Hill slope of
      approximately 3.3. Single channel recordings were obtained by steady-state
      application of glycine (0.3, 1, or 10 microM) to outside-out patches. Single
      channel conductances were mostly 60-90 pS, but smaller conductances of
      approximately 40 pS were also seen (10% of the events) with a relative frequency
      that did not depend on agonist concentration. The time constants of the apparent
      open time distributions did not vary with agonist concentration, but short events
      were more frequent at low glycine concentrations. There was also evidence of a
      previously missed short-lived open state that was more common at lower glycine
      concentrations. The time constants for the different components of the burst
      length distributions were found to have similar values at different
      concentrations. Nevertheless, the mean burst length increased with increasing
      glycine. This was because the relative area of each burst-length component was
      concentration dependent and short bursts were favored at lower glycine
      concentrations. Durations of adjacent open and shut times were found to be
      strongly (negatively) correlated. Additionally, long bursts were made up of
      longer than average openings separated by short gaps, whereas short bursts
      usually consisted of single isolated short openings. The most plausible
      explanation for these findings is that long bursts are generated when a higher
      proportion of the five potential agonist binding sites on the receptor is
      occupied by glycine. On the basis of the concentration dependence and the
      intraburst structure we provide a preliminary kinetic scheme for the activation
      of the homomeric glycine receptor, in which any number of glycine molecules from
      one to five can open the channel, although not with equal efficiency.

PMID- 11981024
TI  - Cations affect the rate of gating charge recovery in wild-type and W434F Shaker
      channels through a variety of mechanisms.
AB  - In this study we examine the effects of ionic conditions on the gating charge
      movement in the fast inactivation-removed wild-type Shaker channel and its W434F
      mutant. Our results show that various ionic conditions influence the rate at
      which gating charge returns during repolarization following a depolarizing pulse.
      These effects are realized through different mechanisms, which include the
      regulation of channel closing by occupying the cavity, the modulation of
      transitions into inactivated states, and effects on transitions between closed
      states via a direct interaction with the channel's gating charges. In generating
      these effects the cations act from the different binding sites within the pore.
      Ionic conditions, in which conducting wild-type channels close at different
      rates, do not significantly affect the rate of charge recovery upon
      repolarization. In these conditions, channel closing is fast enough not to be
      rate-limiting in the charge recovery process. In the permanently P-inactivated
      mutant channel, however, channel closing becomes the rate-limiting step,
      presumably due to weakened ion-ion interactions inside the pore and a slower
      intrinsic rate of gate closure. Thus, variations in closing rate induced by
      different ions are reflected as variations in the rate of charge recovery. In 115
      mM internal Tris(+) and external K(+), Cs(+), or Rb(+), low inward permeation of
      these ions can be observed through the mutant channel. In these instances,
      channel closing becomes slower than in Tris(+)(O)//Tris(+)(I) solutions showing
      resemblance to the wild-type channel, where higher inward ionic fluxes also
      retard channel closing. Our data indicate that cations regulate the transition
      into the inactivated states from the external lock-in site and possibly the deep
      site. The direct action of barium on charge movement is probably exerted from the
      deep site, but this effect is not very significant for monovalent cations.

PMID- 11981025
TI  - Separation and characterization of currents through store-operated CRAC channels
      and Mg2+-inhibited cation (MIC) channels.
AB  - Although store-operated calcium release-activated Ca(2+) (CRAC) channels are
      highly Ca(2+)-selective under physiological ionic conditions, removal of
      extracellular divalent cations makes them freely permeable to monovalent cations.
      Several past studies have concluded that under these conditions CRAC channels
      conduct Na(+) and Cs(+) with a unitary conductance of approximately 40 pS, and
      that intracellular Mg(2+) modulates their activity and selectivity. These results
      have important implications for understanding ion permeation through CRAC
      channels and for screening potential CRAC channel genes. We find that the
      observed 40-pS channels are not CRAC channels, but are instead Mg(2+)-inhibited
      cation (MIC) channels that open as Mg(2+) is washed out of the cytosol. MIC
      channels differ from CRAC channels in several critical respects. Store depletion
      does not activate MIC channels, nor does store refilling deactivate them. Unlike
      CRAC channels, MIC channels are not blocked by SKF 96365, are not potentiated by
      low doses of 2-APB, and are less sensitive to block by high doses of the drug. By
      applying 8-10 mM intracellular Mg(2+) to inhibit MIC channels, we examined
      monovalent permeation through CRAC channels in isolation. A rapid switch from 20
      mM Ca(2+) to divalent-free extracellular solution evokes Na(+) current through
      open CRAC channels (Na(+)-I(CRAC)) that is initially eightfold larger than the
      preceding Ca(2+) current and declines by approximately 80% over 20 s. Unlike MIC
      channels, CRAC channels are largely impermeable to Cs(+) (P(Cs)/P(Na) = 0.13 vs.
      1.2 for MIC). Neither the decline in Na(+)-I(CRAC) nor its low Cs(+) permeability
      are affected by intracellular Mg(2+) (90 microM to 10 mM). Single openings of
      monovalent CRAC channels were not detectable in whole-cell recordings, but a
      unitary conductance of 0.2 pS was estimated from noise analysis. This new
      information about the selectivity, conductance, and regulation of CRAC channels
      forces a revision of the biophysical fingerprint of CRAC channels, and reveals
      intriguing similarities and differences in permeation mechanisms of voltage-gated
      and store-operated Ca(2+) channels.

PMID- 11981026
TI  - Minireview: branded from the start-distinct oncogenic initiating events may
      determine tumor fate in the thyroid.
AB  - Thyroid follicular neoplasms commonly have aneuploidy, presumably due to
      chromosomal instability. This property is associated with a greater malignant
      potential and worse prognosis. Recently, there has been considerable progress in
      our understanding of mechanisms that may account for chromosomal instability in
      cancer cells. Many tumors with chromosomal instability have abnormalities in the
      cell cycle checkpoint that monitors the fidelity of mitosis. Mutations of Bub1 or
      BubR1, genes coding for kinases involved in mitotic spindle assembly checkpoint
      signaling, are found in a small subset of aneuploid tumors. Other components of
      protein complexes responsible for attachment of kinetochores to microtubules, or
      for cohesion between sister chromatids, may also be subject to alterations during
      tumor progression. Here, we also discuss the evidence that certain oncogenic
      events, such as Ras mutations, may predispose cells to chromosomal instability by
      favoring inappropriate posttranslational changes in mitotic checkpoint components
      through activation of upstream kinases during tumor initiation or progression.

PMID- 11981027
TI  - TSH receptor interaction with the extracellular matrix: role on constitutive
      activity and sensitivity to hormonal stimulation.
AB  - Using immunocytochemistry, we have observed that the TSH receptor (TSHR) is
      concentrated at the leading edge of lamellipodia in both cultured human thyroid
      cells and in various transfected cells. This segregation of the receptor is due
      to its interaction with extracellular matrix (ECM) and specially with
      fibronectin. The TSHR, which interacts with the ECM, is known to undergo cleavage
      by a matrix metalloprotease. The homologous LH receptor, which does not interact
      with ECM, is not cleaved. The attachment to the ECM modifies the functional
      properties of the receptor: it increases adenylate cyclase stimulation by
      hormone, whereas PLC stimulation is not modified. Furthermore, the constitutive
      activity of the TSHR is only observed in attached cells, suggesting that it is
      dependent on TSHR interaction with the ECM. Thus, aside from its classical
      properties of hormone binding and signalization through G proteins, the TSHR is
      also involved in cell-matrix interactions, which modulate its functional
      properties.

PMID- 11981028
TI  - AR possesses an intrinsic hormone-independent transcriptional activity.
AB  - Recent research has highlighted the functional importance of chromatin structure
      in transcriptional regulation. We have used Xenopus oocytes as a model system to
      investigate the action of AR in the context of chromatin. By manipulating the
      levels of AR expression, we have observed both agonist-dependent and -independent
      activation by AR. Expression of AR at relatively low levels resulted in strong
      agonist-dependent activation, whereas high levels of AR also led to hormone
      independent activation. By using gel mobility shift and deoxyribonuclease I
      footprinting assays, we demonstrate that AR expressed in Xenopus oocytes binds to
      a consensus androgen response element in vitro in a ligand-independent manner.
      Expression of the coactivators steroid receptor coactivator-1, receptor
      associated coactivator-3, and p300 stimulated both agonist-dependent and 
      independent activation by AR. Furthermore, this hormone-independent activity of
      AR is also observed in mammalian cells. Antagonists such as casodex can inhibit
      hormone-independent activity of AR, and this inhibition appears to correlate with
      the enhanced association with corepressor silencing mediator of retinoid and
      thyroid hormone receptors. Altogether, our studies reveal that AR has a capacity
      to activate transcription in a ligand-independent manner.

PMID- 11981029
TI  - ERbeta has nongenomic action in caveolae.
AB  - ERalpha and ERbeta serve classically as transcription factors, and ERalpha also
      mediates nongenomic responses to E2 such as the activation of endothelial nitric
      oxide synthase (eNOS). In contrast, the nongenomic capacities of endogenous
      ERbeta are poorly understood. We evaluated eNOS activation by E2 in cultured
      endothelial cells that express endogenous ERbeta to determine whether the ERbeta
      isoform has nongenomic action and to reveal the subcellular locale of that
      function. A subpopulation of ERbeta was localized to the endothelial cell plasma
      membrane, overexpression of ERbeta enhanced rapid eNOS stimulation by E2, and the
      response to endogenous ER activation was inhibited by the ERbeta-selective
      antagonist RR-tetrahydrochrysene (THC). eNOS activation through ERbeta was
      reconstituted and shown to occur independent of ERalpha in COS-7 cells, and
      ERbeta protein in COS-7 was directed to the plasma membrane. THC also blunted E2
      activation of eNOS in isolated endothelial cell plasma membranes. Furthermore,
      ERbeta protein was detected and THC attenuated E2 stimulation of eNOS in isolated
      endothelial cell caveolae, and functional ERbeta-eNOS coupling was recapitulated
      in caveolae from transfected COS-7 cells. These findings in the ER-eNOS signaling
      paradigm indicate that endogenous ERbeta has nongenomic action in caveolae.

PMID- 11981030
TI  - Calmodulin is a selective modulator of estrogen receptors.
AB  - In the search for differences between ERalpha and ERbeta, we analyzed the
      interaction of both receptors with calmodulin (CaM) and demonstrated that ERalpha
      but not ERbeta directly interacts with CaM. Using transiently transfected HeLa
      cells, we examined the effect of the CaM antagonist N-(6-aminohexyl)-5-chloro
      naphthalene sulfonilamide hydrochloride (W7) on the transactivation properties of
      ERalpha and ERbeta in promoters containing either estrogen response elements or
      activator protein 1 elements. Transactivation by ERalpha was dose-dependently
      inhibited by W7, whereas that of ERbeta was not inhibited or even activated at
      low W7 concentrations. In agreement with these results, transactivation of an
      estrogen response element containing promoter in MCF-7 cells (which express a
      high ERalpha/ERbeta ratio) was also inhibited by W7. In contrast, transactivation
      in T47D cells (which express a low ERalpha/ERbeta ratio) was not affected by this
      CaM antagonist. The sensitivity of MCF-7 cells to W7 was abolished when cells
      were transfected with increasing amounts of ERbeta, indicating that the
      sensitivity to CaM antagonists of estrogen-responsive tissues correlates with a
      high ERalpha/ERbeta ratio. Finally, substitution of lysine residues 302 and 303
      of ERalpha for glycine rendered a mutant ERalpha unable to interact with CaM
      whose transactivation activity became insensitive to W7. Our results indicate
      that CaM antagonists are selective modulators of ER able to inhibit ERalpha
      mediated activity, whereas ERbeta actions were not affected or even potentiated
      by W7.

PMID- 11981032
TI  - Degradation of RXRs influences sensitivity of rat osteosarcoma cells to the
      antiproliferative effects of calcitriol.
AB  - Several cell lines, including ROS17/2.8 rat osteosarcoma (ROS) cells, contain
      functional VDRs and RXRs but are resistant to the antiproliferative effects of
      calcitriol and retinoids. We explored the role of receptor degradation in this
      hormone resistance. Results of transactivation assays indicated that ROS cells
      contain insufficient amounts of RXR to activate a DR-1 reporter, and Western blot
      analyses of cell extracts showed that the degradation of RXR is accelerated and
      produces an aberrant 45-kDa RXR. We stably expressed functional fluorescent
      chimeras of VDR and RXR [green fluorescent protein (GFP)-VDR; yellow fluorescent
      protein (YFP)-RXR] to evaluate degradation mechanisms and the impact of excess
      receptor expression on antiproliferative effects. Microscopy showed a diminished
      expression of YFP-RXR in ROS cells compared with the expression in CV-1 cells.
      Treatment with inhibitors of proteasomal degradation (lactacystin and MG132)
      selectively enhanced GFP-VDR and YFP-RXR expression and also increased the
      endogenous levels of VDR and RXR. Expression of GFP-VDR had no effect on the
      sensitivity of ROS cells to calcitriol. Increases of RXR levels by YFP-RXR
      expression, drug treatments, or the combination of the two, however, restored the
      growth-inhibitory effects of calcitriol and 9-cis-RA and restored p21 induction
      by calcitriol. These studies revealed that an accelerated and aberrant RXR
      degradation could cause resistance to the antiproliferative effects of calcitriol
      and retinoids in ROS cells.

PMID- 11981033
TI  - Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X
      receptor (BXR) define three pharmacologically distinct classes of nuclear
      receptors.
AB  - The NR1I subfamily of nuclear receptors contains a phylogenetically diverse array
      of receptors related to the mammalian pregnane X receptor (PXR) (NR1I2) and
      constitutive androstane receptor (CAR) (NR1I3). We have carried out an extensive
      comparative analysis of this subgroup with representatives from fish, birds,
      amphibians, and mammals. Four novel receptors were isolated from fish, dog, pig,
      and monkey for this study and combined with a previously reported set of related
      receptors including human PXR, rabbit PXR, mouse PXR, chicken CXR, frog benzoate
      X receptors (BXRalpha, BXRbeta), and human and mouse CAR. A broad range of
      xenobiotics, steroids, and bile acids were tested for their ability to activate
      the ligand binding domain of each receptor. Three distinct groups of receptors
      were identified based on their pharmacological profiles: 1) the PXRs were
      activated by a broad range of xenobiotics and, along with the mammalian PXRs,
      included the chicken and fish receptors; 2) the CARs were less promiscuous, had
      high basal activities, and were generally repressed rather than activated by
      those compounds that modulated their activity; and 3) the BXRs were selectively
      activated by a subset of benzoate analogs and are likely to be specialized
      receptors for this chemical class of ligands. The PXRs are differentiated from
      the other NR1I receptors by a stretch of amino acids between helices 1 and 3,
      which we designate the H1-3 insert. This insert was present in the mammalian,
      chicken, and fish PXRs but absent in the CARs and BXRs. Modeling studies suggest
      that the H1-3 insert contributes to the promiscuity of the PXRs by facilitating
      the unwinding of helices-6 and -7, thereby expanding the ligand binding pocket.

PMID- 11981034
TI  - Molecular recognition of agonist ligands by RXRs.
AB  - The nuclear receptor RXR is an obligate partner in many signal transduction
      pathways. We report the high-resolution structures of two complexes of the human
      RXRalpha ligand-binding domain specifically bound to two different and chemically
      unrelated agonist compounds: docosa hexaenoic acid, a natural derivative of
      eicosanoic acid, present in mammalian cells and recently identified as a
      potential endogenous RXR ligand in the mouse brain, and the synthetic ligand BMS
      649. In both structures the RXR-ligand-binding domain forms homodimers and
      exhibits the active conformation previously observed with 9-cis-RA. Analysis of
      the differences in ligand-protein contacts (predominantly van der Waals forces)
      and binding cavity geometries and volumes for the several agonist-bound RXR
      structures clarifies the structural features important for ligand recognition.
      The L-shaped ligand-binding pocket adapts to the diverse ligands, especially at
      the level of residue N306, which might thus constitute a new target for drug
      design. Despite its highest affinity 9-cis-RA displays the lowest number of
      ligand-protein contacts. These structural results support the idea that docosa
      hexaenoic acid and related fatty acids could be natural agonists of RXRs and
      question the real nature of the endogenous ligand(s) in mammalian cells.

PMID- 11981035
TI  - Characterization of the retinoid orphan-related receptor-alpha coactivator
      binding interface: a structural basis for ligand-independent transcription.
AB  - The retinoid orphan-related receptor-alpha (RORalpha) is a member of the ROR
      subfamily of orphan receptors and acts as a constitutive activator of
      transcription in the absence of exogenous ligands. To understand the basis of
      this activity, we constructed a homology model of RORalpha using the closely
      related TRbeta as a template. Molecular modeling suggested that bulky hydrophobic
      side chains occupy the RORalpha ligand cavity leaving a small but distinct cavity
      that may be involved in receptor stabilization. This model was subject to docking
      simulation with a receptor-interacting peptide from the steroid receptor
      coactivator, GR-interacting protein-1, which delineated a coactivator binding
      surface consisting of the signature motif spanning helices 3-5 and helix 12
      [activation function 2 (AF2)]. Probing this surface with scanning alanine
      mutagenesis showed structural and functional equivalence between homologous
      residues of RORalpha and TRbeta. This was surprising (given that RORalpha is a
      ligand-independent activator, whereas TRbeta has an absolute requirement for
      ligand) and prompted us to use molecular modeling to identify differences between
      RORalpha and TRbeta in the way that the AF2 helix interacts with the rest of the
      receptor. Modeling highlighted a nonconserved amino acid in helix 11 of RORalpha
      (Phe491) and a short-length of 3.10 helix at the N terminus of AF2 which we
      suggest 1) ensures that AF2 is locked permanently in the holoconformation
      described for other liganded receptors and thus 2) enables ligand-independent
      recruitment of coactivators. Consistent with this, mutation of RORalpha Phe491 to
      either methionine or alanine (methionine is the homologous residue in TRbeta),
      reduced and ablated transcriptional activation and recruitment of coactivators,
      respectively. Furthermore, we were able to reconstitute transcriptional activity
      for both a deletion mutant of RORalpha lacking AF2, and Phe491Met, by
      overexpression of a GAL-AF2 fusion protein, demonstrating ligand-independent
      recruitment of AF2 and a role for Phe491 in recruiting AF2.

PMID- 11981036
TI  - Characterization of the human PPARalpha promoter: identification of a functional
      nuclear receptor response element.
AB  - PPARalpha is a nuclear receptor that controls lipid and glucose metabolism and
      exerts antiinflammatory activities. The factors regulating human PPARalpha
      (hPPARalpha) gene expression remain largely unexplored. To study the mechanisms
      controlling hPPARalpha expression, the hPPARalpha gene promoter was identified
      and characterized. First, an alternatively spliced exon within the 5'
      untranslated region of the hPPARalpha gene was identified by RT-PCR. Next, the
      transcription start site was mapped and the hPPARalpha gene promoter was cloned
      and functionally analyzed. Because PPARalpha levels are elevated in tissues
      expressing the hepatocyte nuclear factor-4 (HNF4), such as liver, the regulation
      of hPPARalpha by HNF4 was examined. Transient transfections in HepG2 and Cos
      cells showed that HNF4 enhances hPPARalpha promoter activity. 5'-Deletion and
      mutation analysis of the hPPARalpha promoter identified a regulatory element (RE)
      consisting of a degenerate hexamer repeat with a single nucleotide spacer (direct
      repeat 1), termed alphaHNF4-RE. Gel shift assays demonstrated that HNF4 binds to
      this alphaHNF4-RE. Furthermore, HNF4 increased the activity of a heterologous
      promoter driven by two copies of the alphaHNF4-RE. The nuclear receptor COUP-TFII
      also bound this site and down-regulated basal as well as HNF4-induced hPPARalpha
      promoter activity. Finally, PPARalpha was shown to bind the alphaHNF4-RE, leading
      to an induction of PPARalpha expression in hepatocytes. In summary, the
      organization of the 5'-flanking and untranslated region of the hPPARalpha gene
      was characterized and the hPPARalpha promoter region has been identified.
      Furthermore, these data demonstrate that the hPPARalpha gene is regulated by
      nuclear receptors, such as HNF-4, COUP-TFII, and PPARalpha.

PMID- 11981037
TI  - DNA binding-independent induction of IkappaBalpha gene transcription by
      PPARalpha.
AB  - PPARs are ligand-activated transcription factors that regulate energy
      homeostasis. In addition, PPARs furthermore control the inflammatory response by
      antagonizing the nuclear factor-kappaB (NF-kappaB) signaling pathway. We recently
      demonstrated that PPARalpha activators increase IkappaBalpha mRNA and protein
      levels in human aortic smooth muscle cells. Here, we studied the molecular
      mechanisms by which PPARalpha controls IkappaBalpha expression. Using transient
      transfection assays, it is demonstrated that PPARalpha potentiates p65-stimulated
      IkappaBalpha transcription in a ligand-dependent manner. Site-directed
      mutagenesis experiments revealed that PPARalpha activation of IkappaBalpha
      transcription requires the NF-kappaB and Sp1 sites within IkappaBalpha promoter.
      Chromatin immunoprecipitation assays demonstrate that PPARalpha activation
      enhances the occupancy of the NF-kappaB response element in IkappaBalpha promoter
      in vivo. Overexpression of the oncoprotein E1A failed to inhibit PPARalpha
      mediated IkappaBalpha promoter induction, suggesting that cAMP response element
      binding protein-binding protein/p300 is not involved in this mechanism. By
      contrast, a dominant-negative form of VDR-interacting protein 205 (DRIP205)
      comprising its two LXXLL motifs completely abolished PPARalpha ligand-mediated
      activation. Furthermore, cotransfection of increasing amounts of DRIP205 relieved
      this inhibition, suggesting that PPARalpha requires DRIP205 to regulate
      IkappaBalpha promoter activity. By contrast, DRIP205 is not involved in PPARalpha
      mediated NF-kappaB transcriptional repression. Taken together, these data provide
      a molecular basis for PPARalpha-mediated induction of IkappaBalpha and
      demonstrate, for the first time, that PPARalpha may positively regulate gene
      transcription in the absence of functional PPAR response elements.

PMID- 11981038
TI  - Differential gene regulation by PPARgamma agonist and constitutively active
      PPARgamma2.
AB  - The PPARgamma is a key adipogenic determination factor. Ligands for PPARgamma
      such as antidiabetic thiazolidinedione (TZD) compounds are adipogenic, and many
      adipocyte genes that are activated by TZDs contain binding sites for PPARgamma.
      Like ligands for other nuclear receptors, TZDs can regulate genes positively or
      negatively. Here, we sought to understand the importance of positive regulation
      of gene expression by PPARgamma in adipogenesis. Fusion of the potent viral
      transcriptional activator VP16 to PPARgamma2 (VP16-PPARgamma) created a
      transcription factor that constitutively and dramatically activated transcription
      of PPARgamma-responsive genes in the absence of ligand. Forced expression of VP16
      PPARgamma in 3T3-L1 preadipocytes using retroviral vectors led to adipogenesis in
      the absence of standard differentiating medium or any exogenous PPARgamma ligand.
      Gene microarray analysis revealed that VP16-PPARgamma induced many of the genes
      associated with adipogenesis and adipocyte function. Thus, direct up-regulation
      of gene expression by PPARgamma is sufficient for adipogenesis. TZD-induced
      adipogenesis up-regulated many of the same genes, although some were divergently
      regulated, including resistin, whose gene expression was reduced inVP16-PPARgamma
      adipocytes treated with TZDs. These results show that, although activation of
      PPARgamma by a heterologous activation domain is sufficient for adipogenesis, it
      is not equivalent to TZD treatment. This conclusion has important implications
      for understanding biological effects of the TZDs on adipogenesis and insulin
      sensitization.

PMID- 11981039
TI  - Acyl-coenzyme A dehydrogenases are localized on GLUT4-containing vesicles via
      association with insulin-regulated aminopeptidase in a manner dependent on its
      dileucine motif.
AB  - Insulin-regulated aminopeptidase (IRAP, also termed vp165) is known to be
      localized on the GLUT4-containing vesicles and to be recruited to the plasma
      membrane after stimulation with insulin. The cytoplasmic region of IRAP contains
      two dileucine motifs and acidic regions, one of which (amino acid residues 55-82)
      is reportedly involved in retention of GLUT4-containing vesicles. The region of
      IRAP fused with glutathione-S-transferase [GST-IRAP(55-82)] was incubated with
      lysates from 3T3-L1 adipocytes, leading to identification of long-chain, medium
      chain, and short-chain acyl-coenzyme A dehydrogenases (ACDs) as the proteins
      associated with IRAP. The association was nearly abolished by mutation of the
      dileucine motif of IRAP. Immunoblotting of fractions prepared from sucrose
      gradient ultracentrifugation and vesicles immunopurified with anti-GLUT4 antibody
      revealed these ACDs to be localized on GLUT4-containing vesicles. Furthermore, 3
      mercaptopropionic acid and hexanoyl-CoA, inhibitors of long-chain and medium
      chain ACDs, respectively, induced dissociation of long-chain acyl-coenzyme A
      dehydrogenase and/or medium-chain acyl-coenzyme A dehydrogenase from IRAP in
      vitro as well as recruitment of GLUT4 to the plasma membrane and stimulation of
      glucose transport activity in permeabilized 3T3-L1 adipocytes. These findings
      suggest that ACDs are localized on GLUT4-containing vesicles via association with
      IRAP in a manner dependent on its dileucine motif and play a role in retention of
      GLUT4-containing vesicles to an intracellular compartment.

PMID- 11981040
TI  - Intracellular insulin-responsive glucose transporter (GLUT4) distribution but not
      insulin-stimulated GLUT4 exocytosis and recycling are microtubule dependent.
AB  - To investigate the potential role of microtubules in the regulation of insulin
      responsive glucose transporter (GLUT4) trafficking in adipocytes, we examined the
      effects of microtubule depolymerizing and stabilizing agents. In contrast to
      previous reports, disruption or stabilization of microtubule structures had no
      significant effect on insulin-stimulated GLUT4 translocation. However, consistent
      with a more recent study (Molero, J. C., J. P. Whitehead, T. Meerloo, and D. E.
      James, 2001, J Biol Chem 276:43829-43835) nocodazole did inhibit glucose uptake
      through a direct interaction with the transporter itself independent of the
      translocation process. In addition, the initial rate of GLUT4 endocytosis was not
      significantly affected by microtubule depolymerization. However, these
      internalized GLUT4 compartments are confined to regions just beneath the plasma
      membrane and were not exposed to the extracellular space. Furthermore, they were
      unable to undergo further sorting steps and trafficking to the perinuclear
      region. Nevertheless, these apparent early endocytic GLUT4 compartments fully
      responded to a second insulin stimulation with an identical extent of plasma
      membrane translocation. Together, these data demonstrate that although
      microtubular organization may play a role in the trafficking of GLUT4 early
      endocytic vesicles back to the perinuclear region, they do not have a significant
      role in insulin-stimulated GLUT4 exocytosis, initial endocytosis from the plasma
      membrane and/or recycling back to the plasma membrane.

PMID- 11981041
TI  - Fibroblast growth factor receptor 4 is a target for the zinc-finger transcription
      factor Ikaros in the pituitary.
AB  - Fibroblast growth factor receptors (FGFRs) have been implicated in a multitude of
      endocrine cell hormonal and proliferative properties, and FGFR4 is differentially
      expressed in normal and neoplastic pituitary. We therefore examined the
      functionally important cis-DNA elements and multiprotein complexes implicated in
      the cooperative control of expression of the human FGFR4 gene in pituitary cells.
      Using deletional mapping, we defined a 214-bp (-115/+99) promoter that was
      functional in pituitary GH4 and PRL 235 cells. Overlapping 40- to 50-bp fragments
      of this minimal promoter were examined by EMSA. Interestingly, fragment C (-64/
      26) included potential binding sites for the hematopoietic zinc finger-containing
      transcription factor Ikaros (Ik) flanked by binding sites for Sp and Ets-type
      factors. DNA binding by Ik, Sp, and Ets-like factors was confirmed by
      oligonucleotide competition and supershifting with specific antibodies.
      Transcriptional regulation of FGFR4 by Ik was demonstrated by cotransfection of
      Ik1 with or without Sp1 or Ets overexpression and by disruption of the Ik binding
      site. Although both Ets-1 and Sp1 overexpression stimulated promoter activity,
      mutation of the Ik-binding site completely eliminated the Ik1 effect. Specific Ik
      expression was identified by Western blotting of pituitary GH4 and PRL235 cells
      and localized in primary mouse hormone-producing anterior pituitary cells by
      immunocytochemistry. Our findings point to a new role for Ik outside the
      hematopoietic system and suggest a novel transcriptional contribution with Ets
      and Sp1 in regulation of FGFR4 in the pituitary.

PMID- 11981042
TI  - Two mutations in extracellular loop 2 of the human GnRH receptor convert an
      antagonist to an agonist.
AB  - GnRH regulates the reproductive system through cognate G protein-coupled
      receptors in vertebrates. Certain GnRH analogs that are antagonists at mammalian
      receptors behave as agonists at Xenopus laevis and chicken receptors. This
      phenomenon provides the opportunity to elucidate interactions and the mechanism
      underlying receptor activation. A D-Lys(iPr) in position 6 of the mammalian GnRH
      receptor antagonist is required for this agonist activity (inositol phosphate
      production) in the chicken and X. laevis GnRH receptors. Chimeric receptors, in
      which extracellular loop domains of the human GnRH receptor were substituted with
      the equivalent domains of the X. laevis GnRH receptor, identified extracellular
      loop 2 as the determinant for agonist activity of one of the mammalian
      antagonists: antagonist 135-18. Site-directed mutagenesis of nine nonconserved
      residues in the C-terminal domain of extracellular loop 2 of the human GnRH
      receptor showed that a minimum of two mutations (Val(5.24(197))Ala and
      Trp(5.32(205))His) is needed in this region for agonist activity of antagonist
      135-18. Agonist activity of antagonist 135-18 was markedly decreased by low pH
      (<7.0) compared with GnRH agonists. These findings indicate that D-Lys(iPr)(6)
      forms a charge-supported hydrogen bond with His(5.32(205)) to stabilize the
      receptor in the active conformation. This discovery highlights the importance of
      EL-2 in ligand binding and receptor activation in G protein-coupled receptors.

PMID- 11981043
TI  - A small sequence in the third intracellular loop of the VPAC(1) receptor is
      responsible for its efficient coupling to the calcium effector.
AB  - The stimulatory effect of VIP on intracellular calcium concentration
      ([Ca(2+)](i)) has been investigated in Chinese hamster ovary cells stably
      transfected with the reporter gene aequorin, and expressing human VPAC(1),
      VPAC(2), chimeric VPAC(1)/VPAC(2), or mutated receptors. The VIP-induced
      [Ca(2+)](i) increase was linearly correlated with receptor density and was higher
      in cells expressing VPAC(1) receptors than in cells expressing a similar VPAC(2)
      receptor density. The study was performed to establish the receptor sequence
      responsible for that difference. VPAC(1)/VPAC(2) chimeric receptors were first
      used for a broad positioning: those having the third intracellular loop (IC(3))
      of the VPAC(1) or of the VPAC(2) receptor behaved, in that respect,
      phenotypically like VPAC(1) and VPAC(2) receptor, respectively. Replacement in
      the VPAC(2) receptor of the sequence 315-318 (VGGN) within the IC(3) by its
      VPAC(1) receptor counterpart 328-331 (IRKS) and the introduction of VGGN in state
      of IRKS in VPAC(1) was sufficient to mimic the VPAC(1) and VPAC(2) receptor
      characteristics, respectively. Thus, a small sequence in the IC(3) of the VPAC(1)
      receptor, probably through interaction with G(alphai) and G(alphaq) proteins, is
      responsible for the efficient agonist-stimulated [Ca(2+)](i) increase.

PMID- 11981045
TI  - Basal activation of transcription factor signal transducer and activator of
      transcription (Stat5) in nonpregnant mouse and human breast epithelium.
AB  - Transcription factor Stat5 (signal transducer and activator of transcription) is
      essential for PRL-induced terminal differentiation of mouse mammary epithelial
      cells during pregnancy and lactation and has been implicated in mammary
      tumorigenesis. A new and sensitive immunological method to detect active,
      tyrosine phosphorylated Stat5 in situ revealed that Stat5 is continuously
      activated in luminal epithelial cells of mouse and human breast, not only during
      pregnancy and lactation, but also outside of pregnancy. Examination of virgin
      Stat5a or Stat5b null mice suggested that Stat5a was the primary isoform
      activated in mammary epithelial cells. Basal activation of Stat5 in mammary
      epithelium of virgin wild-type mice was continuous throughout estrous cycle and
      was also detected in 17 of 17 normal human breast tissue specimens analyzed. PRL
      was identified as the principal factor maintaining basal activation of Stat5 in
      mammary epithelium of nonpregnant mice based on several lines of evidence. First,
      administration of PRL, but not GH or epidermal growth factor, uniformly enhanced
      basal activation of Stat5 in luminal mammary epithelial cells. Second,
      hypophysectomy disrupted basal activation of Stat5, an effect that was completely
      reversed by administration of PRL, but only partially by GH. Third, knock-out of
      the PRL receptor gene markedly reduced basal activation of Stat5, an effect that
      was maintained in a normalized endocrine environment after transplanting PRL
      receptor null mammary epithelium into wild-type mice. Continuous activation of
      Stat5 indicates a role of this transcription factor in normal, nonpregnant breast
      epithelial cells, and may shed new light on Stat5 involvement in breast tumor
      promotion.

PMID- 11981044
TI  - Transactivation of the mouse sulfonylurea receptor I gene by BETA2/NeuroD.
AB  - The sulfonylurea receptor 1 (SUR1) plays a key role in regulation of insulin
      secretion in pancreatic beta-cells. In this study we investigated the mechanism
      for tissue-specific expression of the SUR1 gene. A -138/-20 fragment exhibited
      basal promoter activity while the -660/-20 fragment contained a regulatory
      element for tissue-specific expression of the mouse SUR1 gene. A pancreatic beta
      cell-specific transcription factor, BETA2 (beta-cell E box transcription
      factor)/NeuroD, enhanced the promoter activity of the -660/-20 fragment in
      cooperation with E47. Coexpression of a dominant negative mutant of BETA2/NeuroD,
      BETA2(1-233), repressed the promoter activity of the -660/-20 fragment.
      BETA2/NeuroD bound specifically to the E3 element located at -141. The E3
      sequence in a heterologous context conferred transactivation by BETA2/NeuroD in
      HeLa and HIT cells. Mutation of E3 eliminated the stimulatory effect of
      BETA2/NeuroD. Unlike BETA2/NeuroD, neurogenin 3 (ngn3) could not activate the E3
      element in HeLa cells. Overexpression of ngn3 concomitantly increased expression
      of BETA2/NeuroD and SUR1 in HIT cells but not in HeLa cells. These results
      indicate that BETA2/NeuroD induces tissue-specific expression of the SUR1 gene
      through the E3 element. These results also suggest that E3 is specific for
      BETA2/NeuroD, and the stimulatory effect of ngn3 in HIT cells may require factors
      specifically expressed in HIT cells.

PMID- 11981046
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 11981048
TI  - Apoptosis and autoimmunity.

PMID- 11981049
TI  - Percutaneous coronary interventions in patients with renal failure: overcoming in
      stent restenosis?

PMID- 11981050
TI  - Pregnancy after renal transplantation: points to consider.

PMID- 11981051
TI  - Hypercalcaemia and metabolic alkalosis with betel nut chewing: emphasis on its
      integrative pathophysiology.
AB  - BACKGROUND: Events in the gastrointestinal tract that might contribute to a high
      absorption of calcium were simulated in vitro to evaluate why only a small
      proportion of individuals who ingest alkaline calcium salts develop
      hypercalcaemia, hypokalaemia and metabolic alkalosis. METHODS: A patient who
      chewed and swallowed around 40 betel nuts daily developed hypercalcaemia,
      metabolic alkalosis, hypokalaemia with renal potassium wasting, and renal
      insufficiency. The quantities of calcium and alkali per betel nut preparation
      were measured. Factors that might increase intestinal absorption of calcium were
      evaluated. RESULTS: Hypercalcaemia in the index case was accompanied by a high
      daily calcium excretion (248 mg, 6.2 mmol). Circulating levels of 1,25
      dihydroxyvitamin D(3) and parathyroid hormone were low. Hypokalaemia with a high
      transtubular K(+) concentration gradient, metabolic alkalosis, a low excretion of
      phosphate and a very low glomerular filtration rate were prominent features.
      CONCLUSIONS: Possible explanations for the pathophysiology of metabolic alkalosis
      and hypokalaemia are provided. We speculate that a relatively greater
      availability of ionized calcium than inorganic phosphate in the lumen of the
      intestinal tract could have enhanced dietary calcium absorption.

PMID- 11981052
TI  - Very short ischaemia is not the answer.

PMID- 11981053
TI  - Should the allocation of cadaveric kidneys for transplantation be based on HLA
      matching?

PMID- 11981054
TI  - Is atherosclerosis accelerated in young patients with end-stage renal disease?
      The contribution of paediatric nephrology.

PMID- 11981055
TI  - Management of disturbances of calcium and phosphate metabolism in chronic renal
      insufficiency, with emphasis on the control of hyperphosphataemia.
AB  - BACKGROUND: Disturbances of calcium-phosphate (Ca-P) metabolism in chronic renal
      insufficiency (CRI) play an important role not only in bone disease (renal
      osteodystrophy) but also in soft tissue calcification, with an increased risk of
      vascular calcification, arterial stiffness, and worsening of atherosclerosis.
      METHODS: Discussion in order to achieve a consensus on key points relating to
      pathogenesis, clinical assessment, and management of renal osteodystrophy in
      dialysis patients. RESULTS: Secondary hyperparathyroidism develops primarily as a
      consequence of reduced active vitamin D production by the kidneys and phosphate
      retention, with the development of hyperphosphataemia, hypocalcaemia, and
      increased parathyroid hormone (PTH) levels. The same factors over the long term
      cause parathyroid gland hyperplasia and autonomous PTH production (tertiary
      hyperparathyroidism). As hyperphosphataemia and increased CaxP product have been
      associated with increased mortality in dialysis patients, hyperparathyroidism
      should be prevented and managed, starting in the pre-dialysis period, by
      calcium/vitamin D supplementation. Hyperphosphataemia is usually treated by means
      of intestinal phosphate binders, but different types of binders have been used.
      The traditional aluminium-based phosphate binders are certainly effective, but
      have the drawback of side effects due to aluminium absorption (osteomalacia,
      encephalopathy, microcytic anaemia). Calcium-containing phosphate binders
      (calcium carbonate or calcium acetate) have mainly been used for the last 10-15
      years. However, they aggravate metastatic calcification, particularly if they are
      taken together with vitamin D analogues and a high calcium dialysate
      concentration. New calcium- and aluminium-free phosphate binders have recently
      been developed and may be useful, particularly in patients with metastatic
      calcification and/or hypercalcaemic episodes, in order to reduce the phosphate
      burden in the absence of an additional calcium load. New vitamin D analogues and
      calcimimetic drugs are also being developed for PTH suppression, with the goal to
      minimize or even entirely avoid hypercalcaemia and/or hyperphosphataemia. A
      suitable dialysate calcium concentration is important and must take into
      consideration the medical therapy and the calcium balance on an individual
      patient basis. Surgical parathyroidectomy is the ultimate means of treating
      hypercalcaemic hyperparathyroidism, when medical therapy has failed. CONCLUSION:
      Achieving an evidence-based consensus can give clinicians a useful tool for the
      treatment of disturbances of Ca-P metabolism in CRI: this has become an important
      objective in nephrological care, particularly as ageing and increased risk of
      atherosclerosis have become major issues in the dialysis population.

PMID- 11981056
TI  - Secondary hyperparathyroidism: present and future therapeutic implications.

PMID- 11981057
TI  - Chemoattraction of T cells expressing CCR5, CXCR3 and CX3CR1 by proximal tubular
      epithelial cell chemokines.
AB  - BACKGROUND: Chemokines produced by resident renal cells promote the infiltration
      of leukocyte subsets. We have analysed the chemotactic responses of CD3+
      peripheral blood lymphocytes (PBLs) to factors secreted by proximal tubular
      epithelial cells (PTEC), assessing the role of chemokines and chemokine receptors
      in this process. METHODS: By FACS we analysed expression of the chemokine
      receptors CCR5, CXCR3, CX3CR1, CCR2, CXCR1 and CXCR2 on both freshly isolated and
      activated PBLs. Using Boyden chambers we studied the chemotactic activity of
      supernatant from resting and cytokine-stimulated (TNF-alpha and IFN-gamma) PTEC
      towards PBLs. Soluble recombinant chemokines and blocking antibodies were used to
      study the role of individual chemokine receptors. Chemokine secretion by PTEC was
      analysed by ELISA. RESULTS: Only a small proportion of freshly isolated cells
      expressed the chemokine receptors and there was low grade chemotaxis of these
      cells towards cytokine-stimulated PTEC supernatant compared with unstimulated
      PTEC supernatant. After activation, 84% of PBLs expressed CCR5, 90% expressed
      CXCR3 and 19% expressed CX3CR1. There remained low expression levels of CXCR1,
      CXCR2 and CCR2. Activated PBLs showed strong chemotactic responses to supernatant
      from cytokine-stimulated PTEC compared with unstimulated PTEC (P<0.001).
      Chemotaxis of these cells was inhibited by blocking CCR5, CXCR3 and CX3CR1 by
      69%, 71% and 29% respectively, with complete inhibition following combined
      blockade. ELISA showed high levels of the chemokine RANTES/CCL5 (for CCR5) and IP
      10/CXCL10 (for CXCR3) in cytokine-stimulated PTEC supernatant. CONCLUSIONS:
      Chemokines produced by cytokine activated PTEC promote the selective recruitment
      of activated T cells via the receptors, CCR5, CXCR3 and CX3CR1. These receptors
      may be amenable to therapeutic manipulation in renal inflammation.

PMID- 11981058
TI  - The effect of pH and nucleophiles on complement activation by human proximal
      tubular epithelial cells.
AB  - BACKGROUND: Activation of urinary complement proteins in situ by proximal tubular
      epithelial cells (PTEC) may contribute to the mediation of tubulointerstitial
      injury in patients with significant proteinuria. However, the mechanism involved
      is unclear, and the role of changes in urinary pH and in the concentrations of
      urea or ammonia requires further clarification. METHODS: The protein fraction of
      urine samples from nine patients with proteinuria >1.5 g/day was purified. A cell
      ELISA involving cultured HK-2 PTEC was used to investigate the capacity of
      urinary protein to promote the deposition of both C3 and C9 on the cell surface.
      The effect of variations in pH (5.5-8.0) and in the concentration of urea and
      ammonia was also examined. C3 was purified and used to further investigate the
      mechanism of complement deposition. RESULTS: Urine samples from the majority of
      patients induced deposition of C3 and C9 on the surface of HK-2 cells via the
      alternative pathway. This process was maximal at acidic pH values. Preincubation
      of urinary complement or serum with urea or ammonia inhibited C3 deposition.
      Purified C3 incubated with HK-2 cells showed no evidence of activation in the
      absence of other complement components. CONCLUSIONS: These data suggest that
      bicarbonate protects against complement-mediated damage in the lumen by
      increasing the local pH, rather than by inhibiting the generation of ammonia.
      PTEC appear to activate complement through provision of a 'protected site' on
      their surface, rather than by the activation of C3 by convertase-like
      protease(s).

PMID- 11981059
TI  - Reduced 11beta-hydroxysteroid dehydrogenase activity in experimental nephrotic
      syndrome.
AB  - BACKGROUND: The disease state of the nephrotic syndrome is characterized by
      abnormal renal sodium retention that cannot be completely explained by a
      secondary hyperaldosteronism for the following reasons. Firstly, in rats an
      enhanced sodium retention is observed before proteinuria with intravascular
      volume depletion occurs. Secondly, in patients with the nephrotic syndrome,
      volume expansion with hypertension has been reported despite suppression of the
      renin-aldosterone system. Therefore, another mechanism for sodium retention must
      be postulated for this disease state. We hypothesize that this mechanism is a
      reduced 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) activity, a
      phenomenon known to cause enhanced access of cortisol or corticosterone to the
      mineralocorticoid receptor. METHODS: We assessed the 11beta-HSD activity by
      measuring the urinary ratio of tetrahydrocorticosterone (THB) plus 5alpha
      tetrahydrocorticosterone (5alpha-THB) to 11-dehydro-tetrahydrocorticosterone
      (THA) by gas chromatography-mass spectrometry in rats with puromycin
      aminonucleoside (PAN)-induced proteinuria and with adriamycin nephrosis.
      Furthermore, the plasma ratios of corticosterone to 11-dehydrocorticosterone were
      measured. RESULTS: The urinary ratio of (THB+5alpha-THB)/THA increased in all
      animals following injection of PAN or adriamycin, indicating a reduced activity
      of 11beta-HSD. The reduced activity of 11beta-HSD was confirmed by an increased
      plasma ratio of corticosterone to 11-dehydrocorticosterone. The changes in the
      glucocorticoid metabolite ratios were already present before significant
      proteinuria appeared. CONCLUSION: PAN- or adriamycin-treated rats develop
      proteinuria with a reduced activity of 11beta-HSD, a mechanism contributing to
      the abnormal sodium retention in nephrotic syndrome.

PMID- 11981060
TI  - Prolonged calcium transients and myocardial remodelling in early experimental
      uraemia.
AB  - BACKGROUND: Cardiovascular disease is the most common cause of premature death in
      patients with end-stage renal disease, possibly due to a specific 'uraemic
      cardiomyopathy'. This study was designed to investigate the cardiac changes
      induced by a moderate impairment of renal function in a model of uraemia.
      METHODS: Male Wistar rats (n=11) were rendered uraemic by 5/6 nephrectomy or sham
      operated (n=11). After 4 weeks, cardiac dimensions were measured from fixed
      tissue sections using a digital image analysis technique. In parallel groups of
      animals, cardiac myocytes were isolated and studied for evidence of functional
      changes attributable to uraemia. After steady-state field stimulation at 0.5 Hz,
      intracellular Ca(2+) handling (using Fura-2) was investigated. Up to 20
      consecutive transients were averaged as the extracellular Ca(2+) was increased.
      RESULTS: The 5/6 nephrectomy group had a 75% reduction in glomerular filtration
      rate, and a 2- to 3-fold increase in serum urea and creatinine compared with sham
      operated control animals (P<0.0001). However, the blood pressure was found to be
      similar in each group. Histology of the intact hearts (five pairs) showed a
      significant increase in tissue cross-sectional area (14%; P<0.04), cross
      sectional area of the left ventricle (22%; P<0.04), and a significant increase in
      left ventricular wall thickness (15%; P<0.03). In the single cardiac cell study,
      under basal conditions (1-2 mM extra-cellular Ca(2+)) no significant differences
      in intracellular Ca(2+) were observed, but in high extracellular Ca(2+) the
      uraemic cells were slower to return to diastolic intracellular Ca(2+) levels
      (P<0.05). CONCLUSIONS: The data provide evidence of altered myocardial structure
      and function in early experimental uraemia. The changes described are consistent
      with concentric hypertrophy of the left ventricle, which occurs in the absence of
      hypertension.

PMID- 11981061
TI  - How dietary phosphate, renal failure and calcitriol administration affect the
      serum calcium-phosphate relationship in the rat.
AB  - BACKGROUND: The effect of hyperphosphataemia on serum calcium regulation in renal
      failure has not been well studied in a setting in which hypercalcaemia is not
      parathyroid hormone (PTH) mediated. In azotemic rats with a normal serum calcium
      concentration, an increased dietary phosphate burden affects serum calcium
      regulation because of its effects on skeletal resistance to PTH, calcitriol
      production, and possibly intestinal calcium absorption. Our goal was to determine
      how hyperphosphataemia affected the development of hypercalcaemia during
      calcitriol-induced hypercalcaemia and PTH suppression in azotemic rats with
      established hyperparathyroidism. METHODS: Rats underwent a two-stage 5/6
      nephrectomy or corresponding sham operations. After surgery, rats were given a
      high phosphate diet (P 1.2%) for 4 weeks to exacerbate hyperparathyroidism and
      were then changed to a normal diet (P 0.6%) for 2 weeks to normalize serum
      calcium values in the azotemic rats. At week 7, rats were divided into five
      groups and sacrificed after receiving three intraperitoneal doses of calcitriol
      (CTR, 500 pmol/100 g) or vehicle at 24 h intervals. The five groups and dietary
      phosphate content were: group 1, normal renal function (NRF)+0.6% P+vehicle;
      group 2, NRF+0.6% P+CTR; group 3, renal failure (RF)+0.6% P+vehicle; group 4,
      RF+1.2% P+CTR; and group 5, RF+0.6% P+CTR. Both the 0.6% and 1.2% phosphate diets
      contained 0.6% calcium. RESULTS: Serum creatinine values were increased (P<0.05)
      in 5/6 nephrectomized rats (groups 3, 4 and 5), as were serum calcium values
      (P<0.05) in CTR-treated rats (groups 2, 4 and 5) and serum phosphate values
      (P<0.05) in CTR-treated azotemic rats (groups 4 and 5). Serum PTH values were
      suppressed (P<0.05) in CTR-treated hypercalcemic rats (groups 2, 4 and 5) and
      increased (P<0.05) in azotemic rats not given CTR (group 3). In the azotemic
      groups (groups 3, 4 and 5), an inverse correlation was present between serum
      calcium and phosphate in each group, despite a wide variation in serum calcium
      values. The slope of the inverse relationship between serum calcium and phosphate
      was steeper in CTR-treated azotemic rats on a 1.2% phosphate (group 4) diet than
      on a 0.6% phosphate (group 5) diet (P=0.02). Thus, for a similar increase in the
      serum phosphate concentration, serum calcium values decreased more in group 4
      than in group 5. The independent effect of dietary phosphate on serum calcium
      values was also confirmed by analysis of covariance. Finally, the serum calcium
      concentration was shown to be greater for any given serum phosphate value in CTR
      treated rats than in those not on CTR. CONCLUSIONS: In azotemic rats with
      calcitriol-induced hypercalcaemia, the magnitude of hypercalcaemia is affected
      by: (i) the serum phosphate concentration; and (ii) differences in dietary
      phosphate content. Calcitriol administration also acts to shift upwards the
      relationship between serum calcium and phosphate so that a higher serum calcium
      concentration can be maintained for any given serum phosphate value.

PMID- 11981062
TI  - Cytomegalovirus increases collagen synthesis in chronic rejection in the rat.
AB  - BACKGROUND: We have demonstrated previously that cytomegalovirus (CMV) infection
      enhances chronic renal allograft rejection in a rat model. Interstitial fibrosis,
      a characteristic finding for chronic rejection, was also more prominent in CMV
      infected grafts. The effect of CMV on the development of fibrosis in this model
      was investigated here at the molecular level. The collagen/DNA ratio, gene
      expression of type I and III collagen mRNAs and the presence of myofibroblasts
      were examined. METHODS: Transplantations were performed under triple drug
      immunosuppression in a rat strain combination of DA(RT1(a)) and BN(RT1(n)). One
      group of animals was infected with rat CMV and the other was left uninfected. The
      grafts were harvested at different time points post-transplantation. Graft
      histology was evaluated according to the Banff criteria and quantified by the
      chronic allograft damage index (CADI). Total collagen was measured and DNA and
      RNA were extracted from the grafts. Type I and III collagen mRNAs were determined
      by slot blot and in situ hybridizations. Myofibroblasts were demonstrated by
      immunohistochemistry. RESULTS: The time-related increase of the collagen/DNA
      ratio in the CMV-infected grafts was higher than in the uninfected animals,
      correlating with the development of fibrosis at the histology. The expression of
      type I and III collagen mRNAs peaked shortly after transplantation, together with
      the presence of myofibroblasts, with significantly higher peaks in the CMV
      infected grafts compared with the non-infected ones. CONCLUSIONS: CMV increases
      the expression of both type I and III collagens and the accumulation of
      myofibroblasts, and enhances total collagen synthesis in the development of
      interstitial fibrosis in chronic renal allograft rejection.

PMID- 11981063
TI  - Combination treatment with an ET(A)-receptor blocker and an ACE inhibitor is not
      superior to the respective monotherapies in attenuating chronic transplant
      nephropathy in a 'Fisher-to-Lewis' rat model.
AB  - BACKGROUND: Specific endothelin A (ET(A))-receptor blockade and ACE inhibition
      attenuate chronic transplant nephropathy (CTN) in the 'Fisher-to-Lewis' rat
      model. It is unknown (i) which of both pharmacological interventions attenuates
      CTN more effectively and (ii) whether combination therapy exerts additive
      nephroprotection. METHODS: We compared (i) the effects of specific ET(A)-receptor
      blockade with LU 302146 (30 mg/kg bw/day) and ACE inhibition with trandolapril
      (0.3 mg/kg bw/day) and (ii) the effect of a combination therapy of both drugs on
      the development of CTN. Kidneys of Fisher rats were orthotopically grafted to
      Lewis rats. Untreated 'Fisher-to-Lewis' allografts served as controls (TX). All
      animals received low-dose cyclosporin A (1.5 mg/kg body weight) for 10 days post
      transplant to inhibit early acute rejection episodes. The duration of the
      experiment was 36 weeks. Blood pressure (BP) was measured every other week by
      tail plethysmography. Indices of glomerulosclerosis (GS), tubulointerstitial and
      vascular damage, number of glomeruli, total glomerular volume and mean glomerular
      volume were measured using morphometric and stereological techniques,
      respectively. Albuminuria, blood chemistry and haematology were measured at the
      end of the experiment. RESULTS: LU 302146 did not affect systolic BP. In
      contrast, trandolapril and combination treatment significantly reduced systolic
      BP. Histological signs of CTN were almost completely prevented by LU 302146 and
      trandolapril as compared to TX, e.g. GS=0.8+/-0.08 and 0.9+/-0.20 vs 1.8+/-0.21*
      (arbitrary unit; *P<0.001 vs treated groups). Allograft weight was significantly
      lower in treated vs TX animals. Trandolapril and combination therapy, but not LU
      302146 alone, abrogated glomerular hypertrophy, i.e. mean glomerular volume: TX
      2.22+/-0.43, trandolapril 1.61+/-0.38**, LU 302146 2.22+/-0.11, trandolapril+LU
      302146 1.78+/-0.28* (microm(3); *P<0.05 vs control and LU 302146, **P<0.01 vs
      control and LU 302146). Albuminuria was lower in treated compared to TX animals.
      Combination therapy did not confer additional benefit compared to the respective
      monotherapies. CONCLUSIONS: We conclude that ET(A)-receptor blockade abrogates
      GS, tubulointerstitial and vascular damage in the 'Fisher-to-Lewis' model of CTN
      to a similar extent as ACE inhibition. However, only ACE inhibition inhibits
      glomerular hypertrophy. In contrast to ACE inhibition, the effect of ET(A)
      receptor blockade is independent of BP. This finding is consistent with the
      notion that ET(A)-receptor mediated events play a partly BP-independent role in
      the genesis of CTN. Combination therapy exerts no additive nephroprotection.

PMID- 11981064
TI  - Measurements of cortical interstitium in biopsies from human kidney grafts: how
      representative and how reproducible?
AB  - BACKGROUND: The aim of the study was to evaluate how well a biopsy from one
      region of a human renal allograft represented biopsies from other regions
      regarding the renal interstitial tissue assessed by stereology. Furthermore, we
      wanted to evaluate the reproducibility of the measurements. METHODS: Punch
      biopsies (3 mm) from six regions in each kidney were obtained from seven
      explanted renal grafts with varying degrees of clinically diagnosed chronic and
      acute rejection. One kidney, removed for a minor pelvic tumour, served as
      reference material. Using point counting on PAS-stained sections, the volume
      fraction of the interstitial tissue per glomerular cortex
      V(V)(interstitium/cortex) was estimated. From each kidney, two of the six
      biopsies were re-evaluated by the same observer. RESULTS:
      V(V)(interstitium/cortex) varied from 0.25 to 0.78 between the explanted kidneys
      vs 0.26 in the reference kidney. Variations within the kidneys were low,
      expressed by standard deviations (SD) of between 0.04 and 0.06, and coefficients
      of variation (CV) between 0.06 and 0.22. The SD estimated from repeated
      measurements was 0.04 and CV was 0.07. CONCLUSIONS: Biopsies from one region of
      the kidney were found to be representative for estimates of interstitial tissue
      in explanted human kidney grafts, and the degree of reproducibility was high when
      using point counting, as in the present study.

PMID- 11981065
TI  - Do severe systemic sequelae of proteinuria modulate the antiproteinuric response
      to chronic ACE inhibition?
AB  - BACKGROUND: ACE inhibition exerts an antiproteinuric and renoprotective effect.
      However, residual proteinuria is often present. As residual proteinuria is
      associated with a poor renal outcome, identification of its determinants is
      important. We found previously that the systemic sequelae of proteinuria enhance
      renal damage in untreated nephrotic rats. The impact of systemic nephrosis on
      renal therapy response, however, is unclear. In the present study we therefore
      investigated whether the severity of systemic nephrosis, estimated from plasma
      cholesterol, predicts residual proteinuria during ACE inhibition. METHODS: Sixty
      male Wistar rats with established adriamycin nephrosis were studied. Six weeks
      after the induction of nephrosis, rats were stratified for proteinuria and
      treated for 2 weeks with lisinopril (75 mg/l) or vehicle. RESULTS: At the start
      of treatment, median proteinuria was 744 mg/day (95% confidence interval (CI) 609
      860) and plasma cholesterol was 10.4 mmol/l (95% CI 8.0-12.6), reflecting the
      state of systemic nephrosis. Lisinopril, but not vehicle, reduced blood pressure
      and proteinuria (-62%; range -70 to -48; P<0.001). Residual proteinuria was 275
      mg/day, with a wide range (47-1119 mg/day). Pre-treatment proteinuria and pre
      treatment cholesterol correlated positively with residual proteinuria. By
      multivariate analysis (r(2) of model =0.92), both pre-treatment cholesterol and
      pre-treatment proteinuria were independent predictors of residual proteinuria.
      The quantitative impact of this multivariate analysis is illustrated by the
      difference in residual proteinuria between rats with a cholesterol:proteinuria
      ratio less than, compared with greater than, the median (residual proteinuria 298
      mg/day (CI 129-496) vs 439 mg/day (CI 158-670), respectively). Blood pressure
      response was not predicted by the tested predictor variables. CONCLUSIONS: In
      this model of proteinuria-induced renal damage, not only proteinuria as such, but
      also the concomitant nephrotic alterations predict residual proteinuria. Further
      studies, applying specific interventions, are needed to determine which
      components of the systemic derangements could play a causal role in the
      modulation of therapy response.

PMID- 11981066
TI  - Effect of cerivastatin on proteinuria and urinary podocytes in patients with
      chronic glomerulonephritis.
AB  - BACKGROUND: We previously reported urinary podocytes to be a marker of glomerular
      injury. The aim of the present study was to determine whether cerivastatin, a
      newly developed, potent synthetic statin, affects proteinuria and urinary
      podocyte excretion in patients with chronic glomerulonephritis (CGN). METHODS: We
      randomly assigned 40 normotensive hypercholesterolemic patients with CGN to
      receive either cerivastatin 0.15 mg/day (n=20) or placebo (n=20). Subjects
      comprised 24 men and 16 women, with a mean age of 40.8+/-14.4 years; 27 had IgA
      nephropathy and 13 had non-IgA proliferative glomerulonephritis. Treatment was
      continued for 6 months. Plasma total cholesterol, HDL-cholesterol, LDL
      cholesterol and triglycerides, urinary protein excretion and the number of
      podocytes were measured before treatment and at 3 and 6 months after treatment.
      RESULTS: After 6 months, a significant reduction in total cholesterol (P<0.001),
      LDL-cholesterol (P<0.001) and triglycerides (P<0.05), and a significant increase
      in HDL-cholesterol (P<0.001) were observed in the group treated with
      cerivastatin. Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4
      g/day, (P<0.01) in this group, and urinary podocyte excretion decreased from
      1.6+/-0.6 to 0.9+/-0.4 cells/ml (P<0.01). However, placebo showed little effect
      on these lipid levels, urinary protein excretion and urinary podocyte excretion.
      The differences between the cerivastatin group and the placebo group were
      significant (cholesterol, P<0.001; LDL-cholesterol, P<0.001; triglycerides,
      P<0.05; HDL-cholesterol, P<0.001; urinary protein, P<0.01; and urinary podocytes,
      P<0.01). CONCLUSION: Statins such as cerivastatin may be beneficial for
      restoration of injured podocytes in patients with CGN and hypercholesterolaemia.

PMID- 11981067
TI  - Cytoskeletal protein expression and regenerative markers in schistosomal
      nephropathy.
AB  - BACKGROUND: Progression of renal diseases is related to the abnormal regulation
      of cellular and extracellular matrix turnover. Other factors in addition to
      schistosomal antigens may be relevant to the progression of schistosomal
      nephropathy (SN). The validity of markers of fibroblastic differentiation, alpha
      smooth muscle actin (alphaSMA), and vimentin, as well as the regenerative
      activity (PCNA/apoptosis index) in determination of progression of SN in
      comparison to other forms of non-schistosomal nephropathy (non-SN) is
      investigated. METHODS: Three groups were included; group I pure SN (n=16), group
      II a diverse group of non-schistosomal patients with comparable pathologic
      changes on renal biopsy (n=40) and a control group (n=5). Immunohistochemical
      staining of myofibroblasts (alphaSMA and vimentin) and proliferating cells (PCNA)
      and histomorphometric analysis was done. In situ end labelling (ISEL) of DNA was
      used to evaluate apoptosis. RESULTS: No differences in the patterns of
      distribution of positivity of the different studied markers were observed between
      the different nephropathy groups. Both alphaSMA and vimentin were detected in
      glomerular mesangial, tubular epithelial, interstitial inflammatory fibroblast
      like cells and occasionally endothelial cells. PCNA and apoptotic cells were
      detected in tubular epithelial and interstitial cells with paucity of positive
      cells in the glomerulus. Significant positive correlations were detected in group
      I between glomerular sclerosis and interstitial markers including interstitial
      alphaSMA (r=0.609, P=0.001), interstitial vimentin (r=0.812, P=0.00) and
      interstitial apoptosis (r=0.733, P=0.001). On the other hand, glomerulosclerosis
      in group II showed significant positive correlations with predominantly the
      glomerular markers; glomerular alphaSMA (r=0.475, P=0.002), glomerular apoptosis
      (r=0.684, P=0.00) and glomerular PCNA (r=0.691, P=0.00). Interstitial fibrosis
      correlated significantly with interstitial markers in group I including
      interstitial alphaSMA (r=0.837, P=0.00) interstitial vimentin (r=0.929, P=0.00),
      interstitial apoptosis (r=0.807, P=0.00) and interstitial PCNA (r=0.617, P=0.01),
      while in group II it correlated with both interstitial and glomerular markers. In
      addition, the tubulo-interstitial ratio was significantly higher in group I in
      comparison with group II (P=0.024), with no difference between groups II and III.
      CONCLUSIONS: Although SN may start as glomerulopathy associated with increased
      mesangial cellularity, the interstitial rather than the glomerular markers of
      myofibroblastic differentiation and those of cell turnover are playing a crucial
      role in late stages of schistosomal, but not in non-schistosomal nephropathies.

PMID- 11981068
TI  - Glomerulocystic kidney disease in a family.
AB  - BACKGROUND: Glomerulocystic kidney disease (GCKD) is a rare renal disorder, the
      identity of which has long been discussed. GCKD can occur in a familial form with
      autosomal dominant transmission. The presence of GCKD in families affected with
      autosomal dominant polycystic kidney disease (ADPKD) has lent support to the
      hypothesis that GCKD may be an early manifestation of ADPKD. In families with
      hypoplastic forms of GCKD, the HNF-1beta gene has recently been identified.
      METHODS: Three members of a family were evaluated: a girl (case 1) and her
      brother (case 2), who were aged 11 and 12 years, respectively, at the beginning
      of the study, and, subsequently, the girl's son, when he was 4 years old (case
      3). They all had mild renal insufficiency. Clinical, morphological and genetic
      evaluations were performed on 11 members of the family. RESULTS: Case 1. A mild
      reduction in renal length with modest dysmorphology of renal calyces and
      hyperechogenic parenchyma were present when the patient was 11 years old. At the
      age of 29 some small renal cysts were identified, which remained unchanged over
      the next 8 years. Renal dysfunction remained stable. Case 2. A slight reduction
      in size of a hyperechogenic kidney was found. Cysts were seen at the age of 38.
      Renal dysfunction remained unchanged. Case 3. Kidneys were of normal size. Small
      cysts were found at the age of 9 years. In cases 1 and 2, histopathology was
      highly consistent with GCKD. In none of the cases associated pathological
      conditions could be identified. Haplotype reconstruction allowed the exclusion of
      PKD1 and PKD2 genes. No mutation of the HNF-1beta gene was found. CONCLUSIONS:
      The morphological data from the three cases are suggestive of GCKD. The
      involvement of PKD1, PKD2 and HNF-1beta gene mutations was excluded.

PMID- 11981069
TI  - Intracranial aneurysms and dolichoectasia in autosomal dominant polycystic kidney
      disease.
AB  - BACKGROUND: Intracranial saccular aneurysms (ICA) are a known extrarenal
      manifestation of autosomal dominant polycystic kidney disease (ADPKD). In order
      to facilitate the definition of subgroups who are at risk for ICA and to
      determine the prevalence of ICA in these subgroups we studied ADPKD patients with
      a positive family history for a cerebral event, including cerebral stroke (group
      I) and intracranial bleeding or known ICA (group II). METHODS: Within an
      enrolment period of 21 months, 43 ADPKD patients from our outpatient clinic and
      hospital were examined with cerebral magnetic resonance angiography (MRA).
      RESULTS: ICA were detected in six patients (14%). Three out of 32 patients (9.4%)
      in group I and three out of 11 patients (27.3%) in group II had an ICA. A
      dolichoectasia of intracerebral vessels was found in two out of 43 patients
      (4.7%). CONCLUSIONS: Using MRA a high prevalence of ICA was shown only in
      patients with a family history of cerebral bleeding or ICA. A family history for
      cerebral stroke does not imply an elevated risk for ICA. However, dolichoectasia,
      rare in the normal population, was detected in two patients. We recommend
      screening for ICA in patients with a positive family history for cerebral
      bleeding or ICA. Because of potential complications, examiners should direct
      their attention to dolichoectasia in ADPKD patients.

PMID- 11981070
TI  - Gadolinium as an alternative contrast agent for diagnostic and interventional
      angiographic procedures in patients with impaired renal function.
AB  - BACKGROUND: The study was designed to investigate the safety and feasibility of
      gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative
      angiographic contrast agent in patients with impaired renal function and high
      risk for iodinated contrast-induced nephropathy. METHODS: Gadopentetate
      dimeglumine was used as the radiographic contrast agent in 32 diagnostic or
      interventional angiographic procedures in 29 patients (59% diabetics) with severe
      renal insufficiency (average serum creatinine of 3.6+/-1.4 mg/dl). The average
      dose of gadopentetate dimeglumine was 0.34+/-0.06 mmol/kg body weight.
      Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with
      carbon dioxide (n=12). RESULTS: Thirty-two angiographic procedures (24 diagnostic
      angiographies and 8 interventional procedures) were performed in 29 patients. For
      diagnostic purposes, eleven selective renal arteriographies, six angiographies of
      the iliac arteries and lower extremities, and seven venous angiographies of the
      upper extremity and central veins were performed. Interventional procedures
      consisted of two percutaneous transluminal renal angioplasties with stenting,
      four percutaneous peripheral vascular interventions, and two balloon
      angioplasties of a dialysis fistula. None of the patients, except one, had
      evidence of post-procedure contrast material-induced renal failure (increase in
      serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had
      a clinically important increase in serum creatinine level after percutaneous
      transluminal renal angioplasty and stenting, probably due to cholesterol
      embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow
      adequate diagnostic visualization with digital subtraction equipment in all
      cases. CONCLUSIONS: Gadopentetate dimeglumine is an alternative and safe
      radiographic contrast agent for angiography and interventional procedures in
      patients with severe pre-existing renal impairment. In this population with high
      risk for contrast-induced acute renal failure, it is obviously less nephrotoxic
      than iodinated contrast media.

PMID- 11981071
TI  - Pharmacokinetics of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) in normal and uraemic men.
AB  - BACKGROUND: The therapeutic equivalence of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) on
      the suppression of PTH synthesis and secretion has not clearly been established.
      The aim of the present study was to evaluate the pharmacokinetics of
      1,25(OH)(2)D(3) and 1alpha(OH)D(3) after oral and i.v. administration in healthy
      volunteers and uraemic patients. METHODS: Six healthy volunteers and 12 uraemic
      patients were included in the study. With an interval of 2 weeks, 4 microg of
      1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, 4 microg of
      1alpha(OH)D(3) i.v. and 4 microg of 1alpha(OH)D(3) orally were administered.
      Blood samples for analysis of plasma-Ca(2+), plasma-1,25(OH)(2)D(3), and plasma
      PTH were drawn at time 0, 0.25, 0.5, 1, 2, 4, 6, 9, 12, 24, 48, and 72 h. The
      healthy volunteers were studied in all four protocols and the uraemic patients in
      either the 1alpha(OH)D(3) (n=6) or the 1,25(OH)(2)D(3) (n=6) protocol. RESULTS:
      After oral administration of 1,25(OH)(2)D(3) the bioavailability of
      1,25(OH)(2)D(3) was 70.6+/-5.8/72.2+/-4.8% in healthy volunteers/uraemic patients
      (n.s.). After i.v. administration the volume of distribution of 1,25(OH)(2)D(3)
      was similar, 0.49+/-0.14 vs 0.27+/-0.06 l/kg in healthy volunteers vs uraemic
      patients (n.s.), while the metabolic clearance rate of 1,25(OH)(2)D(3) was 57%
      lower in the uraemic patients, 23.5+/-4.34 vs 10.1+/-1.35 ml/min in healthy
      volunteers vs uraemic patients, respectively (P<0.03). The bioavailability of
      1,25(OH)(2)D(3) after i.v. administration of 1alpha(OH)D(3) was 42.4+/
      11.0/42.0+/-2.0% in healthy volunteers/uraemic patients (n.s.); and after oral
      administration of 1alpha(OH)D(3) 42.0+/-2.0/29.8+/-3.1% in healthy
      volunteers/uraemic patients (n.s.). A small, but significant increase in plasma
      Ca(2+) was seen after administration of 1,25(OH)(2)D(3) to the uraemic patients,
      while no increase was seen after administration of 1alpha(OH)D(3). PTH levels
      were significantly suppressed in the healthy volunteers 24 h after administration
      of 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, and 4
      microg of 1alpha(OH)D(3) orally by 35+/-7, 30+/-8, and 35+/-4%, respectively (all
      P<0.03). In the uraemic patients, PTH levels were significantly suppressed after
      administration of 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3)
      orally, and 4 microg of 1alpha(OH)D(3) i.v. by 30+/-10, 45+/-7, and 40+/-7%,
      respectively (all P<0.04). The effect was transitory in the healthy volunteers
      and lasted for at least 72 h in the uraemic patients. CONCLUSION: The present
      study found a 57% lower metabolic clearance rate of 1,25(OH)(2)D(3) in uraemic
      patients, as compared with that of healthy volunteers (P<0.03). The
      bioavailability of 1,25(OH)(2)D(3) following administration of 1alpha(OH)D(3)
      i.v. and orally in both healthy volunteers and uraemic patients was markedly
      lower than after administration of oral 1,25(OH)(2)D(3) (P<0.03). In spite of
      lower plasma-1,25(OH)(2)D(3) levels after administration of 1alpha(OH)D(3), no
      significant difference was observed on the suppressive effect of 4 microg i.v. of
      either 1,25(OH)(2)D(3) or 1alpha(OH)D(3) on the plasma-PTH levels in the uraemic
      patients. This might suggest the existence of an effect of 1alpha(OH)D(3) on the
      parathyroid glands which is independent of the plasma-1,25(OH)(2)D(3) levels,
      that are achieved after oral or i.v. administration of 1alpha(OH)D(3).

PMID- 11981072
TI  - Arterial percutaneous angioplasty in upper limbs with vascular access devices for
      haemodialysis.
AB  - BACKGROUND: The purpose of this study was to evaluate retrospectively the
      clinical context and effectiveness of arterial percutaneous transluminal
      angioplasty (PTA) of arterio-venous fistulae in chronic haemodialysis patients.
      METHODS: Between May 1992 and June 1997, arterial PTA was performed in 33
      patients with a total of 35 angioaccess devices of the upper limbs (18 arterio
      venous fistulae and 17 PTFE grafts). Clinical indications for arterial PTA were
      unexplained acute thrombosis in 12 patients (34.3%), insufficient blood flow in
      13 patients (37.1%), and severe limb ischaemia in 10 patients (28.6%), two of
      whom had skin ulcerations and one had severe neurological damage. Follow-up
      periods varied between 1 and 55 months (mean 15.5 months). RESULTS: PTA was
      attempted in 22 radial, 10 brachial and seven ulnar arteries. Angioplasty was
      successful (i.e. residual stenosis of </=30%) in all but one patient. There were
      no complications. Early re-thrombosis (<1 month) occurred in two of the 12
      patients with acute occlusions. All the angioaccesses of patients with
      insufficient blood flow were improved. Eight of the patients with limb ischaemia
      became symptom free, and two were failures (one had partial healing of skin
      ulcerations and one did not improve). Re-stenosis occurred in six cases (27.3% of
      the 22 angiograms performed) but re-dilatation was performed in only two
      instances. Primary and secondary patencies were 63.5 and 90.6% at 6 months and
      40.8 and 75.6% at 24 months, respectively. CONCLUSION: Chronic arterial lesions
      in upper limbs bearing vascular access devices for haemodialysis may lead to
      thrombosis, ischaemia and insufficient flow for dialysis treatment. PTA is a safe
      and effective technique with a low rate of re-intervention.

PMID- 11981073
TI  - Insomnia in maintenance haemodialysis patients.
AB  - BACKGROUND: Studies in the last 15 years have shown a high prevalence of sleep
      disorders in maintenance haemodialysis (HD) patients. METHODS: To investigate
      whether the new technical and therapeutic advances of the last decade have had a
      positive impact on sleep disturbances in HD patients: 694 patients (384 males,
      310 females) were surveyed using a specific questionnaire; their clinical,
      lifestyle and dialysis data were also recorded. RESULTS: Forty-five per cent of
      patients (n=311; 156 males, 155 females) complained of insomnia, defined either
      by delayed sleep onset and/or night-time waking, and were included in the
      insomnia group; the remainder were used as controls (control group). There was a
      significantly higher risk of insomnia in patients with >12 months on dialysis, in
      patients dialysed in the morning (P<0.003), and in patients with higher
      parathyroid hormone (PTH) levels (P<0.05). Body mass index, body weight gain and
      blood pressure did not differ between the groups, and neither did the dialysis
      parameters. Creatinine and urea plasma levels were higher in the control group vs
      the insomnia group (P<0.001), but there was no difference in haemoglobin
      concentrations or use of erythropoietin, calcitriol and antihypertensive drugs.
      Cigarette smoking, caffeine or alcohol intake were comparable in the two groups.
      The most frequently recorded sleep disorders were night-time waking (92%),
      trouble falling asleep (67%) and early morning waking (62%). Restless leg
      symptoms were described in 52% of patients with insomnia. CONCLUSIONS: The
      prevalence of insomnia in HD patients is still very high; elderly patients, and
      those with longer time on dialysis and high levels of PTH are at major risk of
      insomnia, whereas type of dialysis, haemoglobin levels and behavioural factors do
      not seem to play a critical role in determining this sleep disorder.

PMID- 11981074
TI  - 5-methyltetrahydrofolate restores endothelial function in uraemic patients on
      convective haemodialysis.
AB  - BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the
      development of atherosclerosis. In patients with chronic renal failure, the
      administration of folic acid or its metabolites reduces but does not normalize
      plasma homocysteine concentrations. Furthermore, homocysteine induces endothelial
      dysfunction by an increased inactivation of nitric oxide. METHODS: We examined
      the effect of the active metabolite of folic acid, 5-methyltetrahydrofolate (5
      MTHF), 45 mg/week i.v. for 10 weeks, combined during the last 2 weeks with
      vitamin B12, 500 microg s.c. twice weekly, on homocysteinaemia and endothelial
      function in 15 patients undergoing convective haemodialysis. Endothelial function
      was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated
      dilation (FMD) was recorded during reactive hyperaemia produced by inflation of a
      pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after
      administration of isosorbide dinitrate. Finally, the presence of the thermolabile
      variant of methyltetrahydrofolate reductase (t-MTHFR) was assessed by genotype
      analysis. RESULTS: Plasma homocysteine concentrations fell by 47% after treatment
      with 5-MTHF alone and by a further 13.6% after the addition of vitamin B12. The
      reduction was more marked in homo- and heterozygous patients than in normal
      genotypes for t-MTHFR. Flow-mediated endothelial vasodilation, measured by
      ultrasonography of the brachial artery, improved after administration of 5-MTHF
      (12.52+/- 2.47% vs. 7.03+/-1.65%; P<0.05), but there were no further changes
      following the addition of vitamin B12. CONCLUSIONS: Our study demonstrated that 5
      MTHF administration not only reduced plasma homocysteine but also improved
      endothelial function in uraemic patients undergoing convective haemodialysis.

PMID- 11981075
TI  - Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic
      acid in combination with vitamin B6 and B12.
AB  - BACKGROUND: In a recent uncontrolled retrospective report we suggested that the
      long-term supplementation of high-dose, i.v. folinic acid combined with high-dose
      i.v. pyridoxine was highly effective in correcting plasma total homocysteine
      (tHcy) concentrations in haemodialysis patients. To confirm these findings, we
      conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral
      folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients
      compared with oral folic acid. METHODS: In a 6-month prospective, randomized,
      controlled trial, 60 chronic haemodialysis patients, matched for age, gender,
      dialysis duration, and average screening pre-treatment-fasting tHcy levels, were
      given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral
      calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60
      patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral
      vitamin B12. RESULTS: Fasting tHcy decreased significantly and to a similar
      extent in the three groups after 2 months of treatment and remained stable at 4
      and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3,
      respectively, P=NS). Mean percentage reduction at 6 months was also similar in
      the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively,
      P=NS). CONCLUSIONS: These findings show that the tHcy-lowering effects of high
      dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable,
      suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is
      not due to abnormal folate metabolism. Furthermore, they are compatible with the
      view that other abnormalities are also involved in the impaired clearance of
      homocysteine in uraemic patients.

PMID- 11981076
TI  - Daily haemodialysis improves indices of protein glycation.
AB  - BACKGROUND: Advanced glycation end-products (AGEs) accumulate in uraemia,
      regardless of hyperglycaemic conditions, and may contribute to the onset of some
      long-term complications, such as atherosclerosis, amyloidosis, and
      neurodegenerative processes. In this study, we compare a daily with a standard 3
      times/week dialysis rhythm (DHD and SHD, respectively) in correcting some protein
      glycation indices in end-stage renal disease (ESRD) patients. METHODS: Twenty-one
      normoglycaemic and 11 diabetic patients on chronic haemodialysis (HD) with low
      flux dialysers were studied in a prospective protocol to compare two different
      dialysis schedules, namely: 4 h, 3 times/week (SHD) and 2 h, 6 times/week (DHD).
      The patients were studied before and after 6 months of DHD. To further check the
      effect of DHD on glycation parameters, 4 normoglycaemic HD patients were studied
      in a third step in which they returned for 3 months to the SHD rhythm. Also, 11
      chronic renal failure (CRF) patients not yet on HD and 11 age- and sex-matched
      healthy controls were studied. A new HPLC method was used to measure the
      following glycation indexes on plasma: the early product furosine and the
      advanced products protein-bound and free pentosidine, and two heterogeneous
      classes of low molecular mass (LMM) AGE peptides. RESULTS: All the parameters
      studied showed an accumulation that worsened with the progression of renal
      failure (controls <CRF <HD). Diabetic patients on SHD showed similar levels of
      glycation indexes as non-diabetic patients, except for the early product furosine
      that was notably higher. The shift from SHD to DHD was effective in lowering the
      concentration of all the glycation parameters measured, both in non-diabetic and
      diabetic patients. In the total HD population, LMM-AGEs (MM range of approx. 1.5
      6.0 kDa) detected at 385 nm emission was lowered by 56% (P<0.001) and LMM-AGEs
      detected at 440 nm emission and furosine decreased by 23 and 19%, (P< or =0.001
      and <0.01, respectively). All these three classes of compounds reached
      concentrations comparable with those observed in the CRF patients, even if
      remaining above the control range. The levels of both free and protein-bound
      pentosidine after DHD decreased by 34% (P<0.001) and 22% (P< or =0.05),
      respectively. The return for 3 months to SHD in four non-diabetic DHD patients
      led to a trend toward an increase in all five glycation parameters. CONCLUSIONS:
      This study demonstrates for the first time that a DHD regimen can effectively
      lower the mean levels of glycation-related substances observed in SHD. Therefore,
      DHD can provide a better control of AGE produced in ESRD. This could result in a
      lower incidence of long-term effects of AGE accumulation in HD.

PMID- 11981077
TI  - Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in
      end-stage renal disease patients.
AB  - BACKGROUND: Free immunoglobulin light chains (FLCs) have previously been shown to
      be uraemic toxins. In this work we investigated the effect of haemodialysis and
      haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients.
      METHODS: Serum/plasma proteins were separated by non-reducing SDS-PAGE and
      transferred to a nitro-cellulose membrane. FLCs were detected by specific
      antibodies and an enhanced chemiluminescence detection system. The FLC
      concentrations were calculated. We studied 15 healthy subjects, 10 patients with
      chronic renal failure, 71 patients undergoing haemodialysis treatment and 33
      patients treated with haemodiafiltration. Different membranes were compared: low-
      and high-flux polysulfone membranes, low- and high-flux cellulose triacetate
      membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes.
      RESULTS: Chronic renal failure patients showed elevated FLC concentrations as
      compared with controls. In haemodialysis or haemodiafiltration patients these
      values were even higher. This was mainly due to an increased concentration of FLC
      of the lambda-type. The treatment modality per se did not influence the FLC
      concentrations. Only haemodialysis or haemodiafiltration with the
      polymethylmethacrylate membrane lead to a significant reduction in FLC
      concentrations; however, these did not reach control levels. We did not observe
      differences in FLC levels between patients with different underlying diseases,
      nor did we find a correlation between age or the duration of the dialysis
      treatment and FLC concentrations. We found a positive correlation between FLC
      concentrations at the beginning of dialysis treatment and the amount of IgLCs
      removed during treatment. However, the average FLC level after treatment did not
      reach control values. CONCLUSIONS: Currently available haemodialysis or
      haemodiafiltration treatments are unable to normalize the elevated serum/plasma
      levels of FLCs in end-stage renal disease patients.

PMID- 11981078
TI  - Comparison of blood group versus HLA-dependent transplantation and its influence
      on donor kidney survival.
AB  - BACKGROUND: The advantages of organ allocation based on human leukocyte antigen
      (HLA) typing are controversial. This evaluation compares the results of HLA
      dependent and non-HLA-dependent allocation in the transplantation of donor
      kidneys. METHODS: Seventy-seven donor kidney pairs explanted locally between 1984
      and 1994 were examined. One half of each pair was transplanted locally in Bonn on
      the basis of criteria including blood group, waiting time and currently negative
      cross-match. The other half of these pairs was allocated in accordance with the
      Eurotransplant (ET) criteria. RESULTS: Cold ischaemia time was an average of
      14.02 h in Bonn vs. 24.18 h in the ET group (P<0.0001). The number of HLA
      mismatches was calculated and, for example, for locus A it was 1.13 in Bonn vs.
      0.73 in the ET group (P=0.0003). One-year graft survival for the locally
      transplanted kidneys was 92.2% and, for the ET kidneys, 90.9%. Five-year survival
      was 79.5% vs. 81.7%, respectively. Patient survival after 1 year was 100% vs.
      97.4%, and after 5 years, 93.4% vs. 93.1%. CONCLUSION: The results show that it
      is possible to provide patients with a locally allocated kidney graft that
      enables good function after a short waiting period. This procedure avoids long
      cold ischaemia time and long waiting periods.

PMID- 11981079
TI  - Incidence of diabetes mellitus requiring insulin treatment after renal
      transplantation in patients with hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection has been associated with an
      increased incidence of diabetes mellitus, both in the general population and
      among transplant patients. METHODS: To test this hypothesis, we reviewed the
      records of 1614 patients who had undergone renal transplant at six Spanish
      centres between 1992 and 1998. We established the rate of onset of diabetes
      mellitus requiring >1 month of treatment with insulin (insulin-treated diabetes
      mellitus, I-TDM) among the 177 patients showing HCV antibody seropositivity at
      the time of transplant (HCV+ group). As controls, 177 HCV patients were selected
      who had received a kidney allograft immediately before or after the study
      patients at the same centre. RESULTS: The HCV+ patients were well matched with
      controls in terms of characteristics (except a longer time on dialysis) and
      immunosuppressive treatment. After a mean follow-up of 44 months, 28 cases of I
      TDM were diagnosed (9.6% in HCV+ and 6.2% HCV-, not significant (NS); odds ratio
      1.6; 95% confidence interval 0.75-3.50). The onset of I-TDM was somewhat later in
      HCV+ patients (467 days vs. 292 days in HCV- patients, NS). Multivariate analysis
      identified the following prognostic factors for I-TDM onset: age and BMI at the
      time of transplant, and polycystic kidney disease as the underlying cause of
      chronic renal insufficiency. No correlation was found with HCV positivity or time
      on dialysis. CONCLUSIONS: We were unable to confirm a greater incidence of post
      renal transplant insulin-requiring diabetes in association with HCV infection.
      However, the observed tendency towards such an association suggests that the
      follow-up period would need to be extended.

PMID- 11981080
TI  - Successful treatment of post-transplant Kaposi's sarcoma by reduction of
      immunosuppression.
AB  - BACKGROUND: The aim of this study was to investigate retrospectively the clinical
      presentation, the efficacy of reducing immunosuppression and the consequences of
      this therapeutic approach in Kaposi's sarcoma (KS) developing after renal
      transplantation. METHODS: We reviewed the records of 502 patients who had been
      followed up at our transplantation unit between October 1, 1987 and December 30,
      1998. Twelve patients (2.4%) with KS were included in the study. RESULTS: The
      mean age of KS patients was 38+/-11 years (one female, 11 males). All were on
      prednisone, azathioprine (AZT) and cylcosporin treatment. KS was encountered at a
      mean of 18+/-10 months post-renal transplantation. Typical Kaposi's lesions were
      present in the skin of 11 out of l2 patients. In the only patient without skin
      involvement, who died from haemophagocytic histiocytic syndrome caused by
      septicaemia, KS was diagnosed post-mortem in a lymph node. In five patients only
      skin involvement was present, while the others also had visceral involvement
      (oropharynx in two patients, trachea and lung in three, lymph node in two,
      stomach and duodenum in two). Cyclosporin was stopped within 1 month after KS
      diagnosis, and AZT was stopped in three patients. Both cutaneous and visceral KS
      manifestations disappeared and no patient was lost due to KS. During a follow-up
      period 46+/-19 months, KS recurred in the lungs in one patient together with lung
      tuberculosis, while he was on prednisone and AZT. Two patients lost their graft
      due to chronic rejection. The remaining eight patients currently have a
      functioning graft with a mean creatinine level of 1.4+/-0.5 mg/dl. CONCLUSION: KS
      is the most frequent post-transplant neoplasia (80%) in our country. In the
      present study cohort, half of the patients had visceral involvement. Reduction or
      discontinuation of immunosuppression caused complete remission in all patients
      without surgical intervention, chemotherapy or radiotherapy.

PMID- 11981081
TI  - Dietary fish oil does not influence acute rejection rate and graft survival after
      renal transplantation: a randomized placebo-controlled study.
AB  - BACKGROUND: Dietary fish oil, rich in omega-3 polyunsaturated fatty acids,
      decreases TNF-alpha, IL-1beta and IL-2 levels, which may benefit renal transplant
      recipients. To explore this possibility, we studied the effect of fish oil on the
      incidence of acute rejection, in situ expression of interleukins (TNF-alpha, IL
      1beta and IL-2) and renal function after renal transplantation. METHODS: In a
      double-blind clinical trial, 86 subjects with no immunological risk randomly
      received either 6 g/day of fish oil (fish oil group; n=46) or soy oil (control
      group; n=40) during the first 3 months after transplantation. The mRNA expression
      of interleukins (TNF-alpha, IL-1beta and IL-2) was determined by RT-PCR using
      fine-needle aspiration during follow-up (at baseline and the 1st, 2nd and 3rd
      month after renal transplantation), as well as during acute rejection episodes
      and after anti-rejection therapy. The glomerular filtration rate was determined
      at baseline, and at 1 and 3 months post-graft by [(51)Cr]EDTA clearances.
      RESULTS: The incidence of acute rejection during the first post-transplant year
      was similar in both groups (44 vs. 47%), as was 1-year graft survival (86 vs.
      89%). There were no differences between groups in overall renal expression of
      interleukins in patients who did not suffer rejections during the study. At
      rejection episodes, the fish oil group showed a trend toward a lower renal
      expression of TNF-alpha (3.7+/-6.8 vs. 15+/-18.6 TNF-alpha/actin, ratio of
      arbitrary optical units; P=0.05). In addition, a trend toward a lower IL-1beta
      expression after therapy was observed in the fish oil group (49.3+/-54 vs. 84.4+/
      59 IL-1beta/actin, ratio of arbitrary optical units; P=0.05). However, the
      severity of acute rejections (Banff criteria) as well as renal function after
      anti-rejection treatment were similar in both groups. Finally, a greater
      reduction in triglyceride levels was observed in the fish oil group compared with
      the control group (-6.6+/-52.7 vs. 12.7+/-40.2%; P<0.05). CONCLUSIONS: Treatment
      with fish oil during the first 3 months post-transplantation does not influence
      acute rejection rate and has no beneficial effect on renal function or graft
      survival.

PMID- 11981082
TI  - Long-term renal allograft outcome after simultaneous kidney and pancreas
      transplantation.
AB  - BACKGROUND: In selected young patients with type 1 diabetes mellitus and end
      stage renal failure, simultaneous pancreas and kidney (SPK) transplantation is
      the treatment of choice. We conducted a retrospective, case-controlled study to
      compare the function, survival and pathology of renal allografts after SPK and
      kidney-alone (KA) transplantations. METHODS: We studied 26 consecutive SPK
      patients and 67 KA controls matched for time of transplantation. Renal function
      was assessed by routine evaluation of serum creatinine and its course by the
      1/serum creatinine vs time curve. Histologic evaluation of early biopsies (0-3
      months post-transplantation, n=63), intermediate biopsies (3 months-1 year, n=75)
      and late biopsies (after 1 year, n=35) were performed by two independent
      reviewers. RESULTS: SPK and KA recipients differed significantly with regard to
      donor and recipient age, time on the waiting list, HLA sensitization, renal cold
      ischaemia time (CIT) and the incidence of delayed graft function. Acute rejection
      was more frequent after SPK than KA (54 vs 27%; P=0.01), despite higher trough
      levels of calcineurin inhibitors. After SPK and KA, actuarial patient and renal
      allograft survival and renal function were comparable at 1 and 4 years. Severe
      chronic lesions, especially vascular lesions, and calcineurin-inhibitor
      nephrotoxicity were more frequent in intermediate and late biopsies in the SPK
      group. CONCLUSIONS: We confirmed that patient and graft survival is comparable
      between SPK and KA recipients. Despite the use of optimal organs and shorter CIT
      in SPK, renal graft function was not different in the two groups. Histologic
      chronic lesions were more severe in SPK than in KA recipients. This might be
      caused by acute rejection episodes or be due to more severe nephrotoxicity after
      SPK, because of higher doses of calcineurin inhibitors, or higher sensitivity to
      calcineurin-inhibitor nephrotoxicity.

PMID- 11981083
TI  - Lack of renoprotective effect of theophylline during aortocoronary bypass
      surgery.
AB  - BACKGROUND: The incidence of acute renal failure (ARF) after cardiac surgery
      remains high, despite improvements in surgical techniques and perioperative care,
      and is associated with an unacceptably high mortality. The adenosine receptor
      antagonist theophylline has been shown to confer some benefit in experimental and
      clinical ARF due to ischaemia, contrast media and various nephrotoxic agents.
      METHODS: In a double-blind, randomized, placebo-controlled trial, the
      effectiveness of theophylline for prevention of renal impairment after elective
      coronary artery bypass grafting (CABG) was evaluated. Fifty-six patients with
      normal renal function received a bolus of 4 mg/kg and a subsequent continuous
      infusion of 0.25 mg/kg/h theophylline (n=28) or isotonic saline (n=28) for up to
      96 h. Serum creatinine concentrations were measured preoperatively and daily
      until day 5 after surgery, and the glomerular filtration rate (GFR) ([(51)Cr]EDTA
      clearance) was determined preoperatively, and at days 1, 3 and 5 after surgery.
      RESULTS: Serum creatinine and GFR were the same in both groups. The number of
      patients with increases of serum creatinine > or =0.4 mg/dl were five in the
      theophylline group and four in the placebo group. Volumes of infused fluid and
      urine volumes were not different between groups, both ranging from approximately
      7.5 to 8 l during the first 24 h after surgery. The number of patients with
      termination of study medication due to presumed side effects was not different
      between placebo and theophylline groups. CONCLUSIONS: Theophylline administration
      for renal protection after CABG appears to be ineffective in a pilot study in
      well-hydrated patients. However, the statistical power of our study was not
      sufficient to exclude a possible protective effect of theophylline. The present
      study demonstrated the feasability of a larger trial with theophylline or one of
      the new specific adenosine A1 receptor antagonists in the setting of ARF after
      cardiac surgery.

PMID- 11981084
TI  - Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations
      in haemodialysis patients receiving high-dose folic acid supplementation.
AB  - BACKGROUND: Hyperhomocysteinaemia, which is considered to be induced by
      impairment of the remethylation pathway in patients with chronic renal failure
      (CRF), cannot be cured solely by folic acid therapy. In the present study, we
      investigated the additional benefit of administration of methylcobalamin, which
      is a co-enzyme in the remethylation pathway, on lowering total homocysteine
      (tHcy) plasma concentrations in haemodialysis (HD) patients receiving high-dose
      folic acid supplementation. METHODS: In order to assess the efficacy on lowering
      plasma tHcy levels (fasting concentration), 21 HD patients, were randomly
      assigned and provided folic acid supplementation: 15 mg/day orally (group I,
      n=7); methylcobalamin 500 mg intravenously after each HD, in addition to folic
      acid (group II, n=7); or vitamin B(6) (B(6)), 60 mg/day orally, in addition to
      folic acid and methylcobalamin (group III, n=7). All patients were treated for 3
      weeks. A methionine-loading test was conducted before and after supplementation.
      The following measurements were also made before and after supplementation for
      each group: serum folic acid, B(6), and vitamin B(12) (B(12)) concentrations
      (including measurement of proportion of methylcobalamin fraction). Twelve HD
      patients receiving methylcobalamin alone served as the HD control group and seven
      healthy volunteers served as the normal control group for this study. RESULTS: In
      our randomized HD patients the proportions of methylcobalamin fraction (48.3+/
      7.5%) and plasma vitamin B(6) concentration (2.9+/-1.1 ng/ml) were significantly
      lower than in the normal controls (methylcobalamin 58.7+/-2.2%, P<0.01; B(6)
      20.1+/-10.8 ng/ml, P<0.01), while folic acid and vitamin B(12) were not
      significantly different from the normal controls. Mean percentage reduction in
      fasting tHcy was 17.3+/-8.4% in group I, 57.4+/-13.3% in group II, 59.9+/-5.6% in
      group III, and 18.7+/-7.5% in HD controls. The power of the test to detect a
      reduction of tHcy level was 99.6% in group II and 99.9% in group III when type I
      error level was set at 0.05. Groups II and III had normal results for the
      methionine-loading test after treatment. Treatment resulted in normalization of
      fasting tHcy levels (<12 ng/ml) in all 14 patients treated by the combined
      administration of methylcobalamin and supplementation of folic acid regardless of
      whether there was supplementation of vitamin B(6). CONCLUSION: The benefit of
      methylcobalamin administration on lowering plasma tHcy levels in HD patients was
      remarkable. Our study suggested that both supplementations of high-dose folic
      acid and methylcobalamin are required for the remethylation pathway to regain its
      normal activity. This method could be a therapeutic strategy to combat the risk
      associated with atherosclerosis and cardiovascular disease in patients with
      chronic renal failure.

PMID- 11981085
TI  - A new acute inflammatory syndrome related to the introduction of mycophenolate
      mofetil in patients with Wegener's granulomatosis.
AB  - Mycophenolate mofetil (MMF) is increasingly used for prevention of allograft
      rejection and to treat immune disorders. We report the development of an acute
      inflammatory syndrome in two patients with Wegener's granulomatosis after MMF was
      introduced, because of persistent renal and systemic disease activity despite
      cyclophosphamide treatment. Within 1 week both patients developed an acute
      inflammatory syndrome, characterized by fever, arthralgias and muscle pain. No
      infection could be detected and no indications for increased Wegener's activity
      were present. MMF was stopped resulting in a rapid and complete resolution of the
      syndrome. A rechallenge with 2 g of MMF in the second patient resulted in a
      relapse of the syndrome within 4 days. There was an association between symptoms
      and increased levels of mycophenolic acid (MPA) acyl glucuronide and serum
      interleukin-6, suggesting the induction of inflammatory cytokines by MPA acyl
      glucuronide as the cause of the syndrome. Therefore, special attention should be
      given to side effects such as fever, arthralgias and muscle pain when treating
      patients with Wegener's granulomatosis during the active phase. Because this side
      effect of MMF may also occur after solid organ transplantation and in other
      immune disorders, pharmacokinetic profiling of MPA and MPA acyl glucuronide is
      needed in future studies with MMF.

PMID- 11981086
TI  - The child with initially refractory skin infection after renal transplantation.

PMID- 11981087
TI  - An uncommon cause of metabolic acidosis in a haemodialysis patient.

PMID- 11981088
TI  - Anuria and cold left leg.

PMID- 11981089
TI  - Pseudoaneurysm with severe haematuria in renal allograft after renal biopsy
      treated by percutaneous embolization.

PMID- 11981091
TI  - High dose of bolus iron vs. low dose of weekly infusion: bolusing high dose, a
      recipe for iron toxicity?

PMID- 11981092
TI  - Fluid restriction in dialysis patients.

PMID- 11981093
TI  - Haemolytic uraemic syndrome following mumps, measles, and rubella vaccination.

PMID- 11981094
TI  - Haemoperfusion may be useful in phenprobamate and polypharmacy intoxication of
      paediatric patients.

PMID- 11981095
TI  - Anodipsia nervosa a variant of anorexia in patients with end-stage renal disease.

PMID- 11981096
TI  - Anaphylactic reaction during haemodialysis on AN69 membrane in a patient
      receiving angiotensin II receptor antagonist.

PMID- 11981097
TI  - Immunological reaction against erythropoietin causing red-cell aplasia.

PMID- 11981098
TI  - Symptomatic hypoglycaemia during haemodialysis in a non-diabetic patient with
      acute hepatitis.

PMID- 11981099
TI  - Desmoid tumours following long-term Tenckhoff peritoneal dialysis catheters.

PMID- 11981100
TI  - Intraperitoneal metoclopramide causing a movement disorder.

PMID- 11981102
TI  - Enoxaparin in unstable angina/non-ST-segment elevation myocardial infarction:
      treatment benefits in prespecified subgroups.
AB  - BACKGROUND: Two large-scale phase III clinical trials, the Efficacy and Safety of
      Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) trial and the
      Thrombolysis in Myocardial Infarction (TIMI) 11B study, have shown the low
      molecular-weight heparin, enoxaparin, to be more effective than unfractionated
      heparin (UFH) in reducing the risk of death and severe cardiac events in patients
      with rest unstable angina and/or non-ST-segment elevation myocardial infarction
      (NSTEMI). However, patients with NSTEMI acute coronary syndromes are a
      heterogeneous group. METHODS: A meta-analysis using pooled data from ESSENCE and
      TIMI 11B was performed to examine the efficacy of enoxaparin in different patient
      subgroups. In addition, a statistical model was developed to test which factors
      best predicted an enhanced treatment effect. RESULTS: Enoxaparin was more
      effective than intravenous dose-adjusted UFH in reducing the incidence of the
      composite endpoint (including death, myocardial infarction or recurrent angina
      prompting urgent revascularization) in the majority of subgroups at 43 days after
      randomization. Univariate analyses revealed that there was a greater benefit with
      enoxaparin in patients with ST-segment deviation or elevated cardiac enzyme
      markers on admission, women, nonsmokers and patients with characteristics
      indicative of higher cardiac risk, including prior percutaneous coronary
      interventions, being at least 65 years old, prior angina and prior aspirin use.
      Multivariate statistical modelling of treatment effect revealed that ST-segment
      depression and electrocardiographic changes were the best predictors of an
      enhanced treatment effect. CONCLUSIONS: These data reinforce previous evidence
      suggesting that enoxaparin administered subcutaneously twice daily may be
      considered as an alternative to intravenous UFH in the acute treatment of a broad
      range of patients with unstable coronary artery disease.

PMID- 11981103
TI  - "Hot" unstable angina--is it worse than subacute unstable angina? Results from
      the GUARANTEE Registry.
AB  - BACKGROUND AND METHODS: Because time to presentation to the hospital affects time
      to treatment and is known to be important in acute myocardial infarction, we
      evaluated this variable in patients with unstable angina/non-ST segment elevation
      myocardial infarction (UA/NSTEMI). Among 2909 consecutive patients with UA/NSTEMI
      admitted to 35 hospitals in 6 geographic regions of the United States, we
      compared patients with acute (onset of pain <12 hours before admission) and
      subacute (onset >12 hours) unstable angina. RESULTS: Patients with "hot" (acute)
      unstable angina presented more often to the emergency department and were
      subsequently admitted more often to an intensive care unit. Hospital
      administration of medications did not differ between the two groups, with the
      exception of heparin, which was paradoxically used more often in subacute
      patients (p<0.001). All cardiac invasive procedures were undertaken less often in
      the acute patients (catheterization, 41.4% vs. 58.7%, p=0.001; percutaneous
      coronary intervention, 11.3% vs. 21.1%, p=0.001; coronary artery bypass grafting,
      5.6% vs. 12.0%, p=0.001). A greater percentage of acute patients were found to
      have no significant coronary artery disease at cardiac catheterization (20.1% vs.
      15.0%, p=0.006). Mortality did not differ between the two groups; however, the
      composite endpoint of death and MI favored the acute patients (1.3% vs. 2.2%,
      p=0.032). CONCLUSIONS: Contrary to our initial hypothesis, "hot" UA patients
      tended to be at lower risk than patients with subacute presentation, highlighting
      the fact that patients with UA/NSTEMI remain at high risk even after the initial
      12-hour period.

PMID- 11981104
TI  - Fibrinolytic variables in postmenopausal women with unstable coronary artery
      disease.
AB  - OBJECTIVES: Many women with typical anginal chest pain have normal coronary
      angiograms. The pathogenetic mechanisms behind the chest pain in these patients
      is unknown but may be due to altered fibrinolytic function enhancing thrombosis
      formation. We evaluated the two key components of the fibrinolytic system, tissue
      type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)
      in women with clinical signs of unstable coronary artery disease (CAD). METHODS
      AND RESULTS: 158 patients with unstable CAD and 101 controls were examined. Of
      the patients 16% had normal vessels and 84% coronary atherosclerosis at coronary
      angiography. Mean plasma concentration of t-PA-ag, but not of PAI-1-act was
      higher in patients than in controls (t-PA-ag: 2.12 (2.05;2.19) vs. 1.98
      (1.89;2.07), p<0.05; PAI-1-act: 1.55 (1.35;1.74) vs. 1.49 (1.24;1.73), p=n.s.).
      Patients with coronary atherosclerosis had significantly higher mean plasma
      levels of both t-PA-ag and PAI-1-act than patients with normal coronary vessels
      (t-PA-ag: 2.16 (2.08;2.33) vs. 1.94 (1.78;2.10), p<0.05; PAI-1-act: 1.68
      (1.47;1.90) vs. 0.82 (0.43;1.21), p<0.01), and these differences were seen
      whether markers of myocardial damage were elevated or not. Mean plasma levels of
      PAI-1-act in patients with normal coronary vessels were even lower than in the
      control group (p<0.05). Almost all significant differences in mean plasma t-PA-ag
      and PAI-1-act disappeared after adjustments for known covariates. CONCLUSION: Our
      results indicate, regardless of myocardial marker elevation or not, an activated
      fibrinolytic system in postmenopausal women with unstable CAD and coronary
      atherosclerosis, but not in the same group of patients with normal coronary
      vessels. This argues against reduced fibrinolytic capacity in the latter patients
      and therefore against thrombosis formation as the cause of chest pain in these
      women. However, we cannot exclude that the differences can be an effect of
      inequality among some common risk factors between the groups.

PMID- 11981105
TI  - Atrial fibrillation and antithrombotic treatment in Italian hospitalized
      patients: a prospective, observational study.
AB  - BACKGROUND: We studied the prevalence of atrial fibrillation within a large
      Italian inpatient population, and evaluated the use of antithrombotic therapy
      among these individuals. METHODS: A prospective cross sectional study (Phase 1)
      with a 1-year follow-up period (Phase 2) was conducted at a single Italian
      centre. During Phase 1, we conducted a chart review of all inpatients on 5
      separate days, each 1 month apart, between January and May 1999. During Phase 2,
      at 1-year of follow-up, patients or their families were contacted to document the
      occurrence of new clinical events, as well as current antithrombotic therapy use.
      RESULTS: A total of 3121 patient charts were reviewed. The prevalence of atrial
      fibrillation was 7.2%. Of these 224 patients, 21.3% were on oral anticoagulants,
      29.7% on antiplatelets, while 49% received neither. Patients on oral
      anticoagulants were significantly younger (mean age 72.3 years) than those on
      antiplatelets (mean age 80.6 years; p<0.001) or neither therapy (mean age 80.7
      years; p<0.001). At 1 year follow up, an acute ischaemic stroke occurred among
      7.4% of the 121 contacted patients. Among patients with chronic atrial
      fibrillation [98], 25.5% were receiving an oral anticoagulant. CONCLUSIONS:
      Despite clear evidence from clinical trials, oral anticoagulants are
      significantly underused among patients with chronic atrial fibrillation. Methods
      should be developed to improve both physician and patient knowledge about the
      overall benefits of anti-thrombotic therapy among these individuals.

PMID- 11981106
TI  - Usefulness of reperfusion ventricular arrhythmias in non-invasive prediction of
      early reperfusion and sustained coronary artery patency in acute myocardial
      infarction.
AB  - BACKGROUND: Established tenets of occurrence of reperfusion ventricular
      arrhythmias in acute myocardial infarction (AMI) do not provide insight into the
      timing of achieving reperfusion or whether coronary artery patency is sustained.
      We assessed the significance of ventricular arrhythmias in the non-invasive
      prediction of timely reperfusion and sustained restoration of coronary patency
      after thrombolysis in patients with AMI. METHODS: 24-hour Holter monitors were
      placed in 163 patients with an AMI before administration of thrombolytic therapy.
      Patients were classified into 3 groups of early (within 2 hours) or late
      reperfusion, or no-reperfusion, according with clinical and continuous ST-segment
      electrocardiographic criteria. Ventricular fibrillation, ventricular tachycardia
      (VT) and accelerated idioventricular rhythm (AIVR) were also categorized as
      having occurred early (within the first 2 hours) or late (after the first 2-hour
      period). Angiographic confirmation of coronary patency was determined 2 to 6 days
      after AMI. RESULTS: Early reperfusion was predicted by early sustained AIVR in
      86% of patients and early non-sustained AIVR in 62.5% of patients, with
      sensitivity 38% and 77%, and specificity 96% and 69%, respectively; p<0.0001.
      Late non-sustained AIVR was commonly seen in early and late reperfused patients
      (92-97%) as well as in non-reperfused patients (74%). Sustained coronary patency
      was predicted by early sustained AIVR in 93% of patients, as well as by early non
      sustained AIVR in 86% of patients and late non-sustained AIVR in 79% of patients,
      with sensitivity 22%, 55% and 94%, and specificity 95%, 71% and 18%,
      respectively; p<0.05. CONCLUSION: Only the occurrence of sustained AIVR, and
      probably early non-sustained AIVR convey useful information about both early
      reperfusion and sustained coronary artery patency. The absence of AIVR does not
      preclude successful thrombolysis.

PMID- 11981107
TI  - High dose and short-term streptokinase infusion in patients with pulmonary
      embolism: prospective with seven-year follow-up trial.
AB  - BACKGROUND: High dose and short-term streptokinase infusion has proved to improve
      survival among few patients with pulmonary embolism and cardiogenic shock,
      without increasing hemorrhagic complications. However its efficacy and safety in
      terms of long follow-up and in major number of patients requires to be
      established. METHODS: Patients with pulmonary embolism proved through high
      probability V/Q lung scan, suggestive echocardiogram, or deep venous thrombosis
      were enrolled. All were assigned to receive 1,500,000 IU in one-hour
      streptokinase infusion. The primary end point was efficacy and safety of
      streptokinase regimen in terms of pulmonary arterial hypertension, right
      ventricular dysfunction, perfusion abnormalities, recurrence, mortality and
      hemorrhagic complications. In long-term follow-up, we assessed functional class,
      recurrence, chronic pulmonary arterial hypertension, postthrombotic-syndrome and
      mortality. RESULTS: A total of 40 consecutive patients (47.3+/-15.3 years of age)
      with large or massive pulmonary embolism were enrolled. In 35 patients high dose
      and short-term streptokinase regimen reversed acute pulmonary arterial
      hypertension, clinical and echocardiographic evidence of right ventricular
      dysfunction and improved pulmonary perfusion without increasing hemorrhagic
      complications. In acute phase 5 patients died, necropsy study performed in 4
      patients showed massive pulmonary embolism and right ventricular myocardial
      infarction, without significant coronary arterial obstruction. Risk factors for
      mortality and recurrence were: right ventricular global hypokinesis (p<0.0001), 6
      hours or over between onset symptoms and streptokinase regimen (p=0.02), severe
      systolic pulmonary arterial hypertension (p=0.001) right ventricular hypokinesis
      (p=0.001), hypoxemia (p=0.02) and right ventricular acute myocardial infarction
      (p<0.0001). Right ventricular hypokinesis (p=0.02) was the only independent risk
      factor for recurrence. In a seven-year follow-up of the original 35 patients who
      survived in acute phase, 2 patients were lost and 33 are alive, in functional
      class I, without recurrence or chronic pulmonary arterial hypertension.
      CONCLUSIONS: Our report indicates that among properly selected high-risk PE
      patients, short-term streptokinase infusion is effective and safe.

PMID- 11981108
TI  - Anti-vWf antibodies induce GPIbalpha and FcgammaRII mediated platelet aggregation
      only at low shear forces.
AB  - BACKGROUND/METHODS: Anti-von Willebrand factor (vWf) antibody mediated platelet
      activation was studied using 2 monoclonal anti-vWf antibodies promoting the
      binding of vWf to GPIbalpha: 1C1E7 (IgG2a) reacting with the vWf N-terminus and
      75H4B12 (IgM), characterized in this paper and studied in association with 1C1E7.
      RESULTS: 75H4B12 binds to an N-terminal epitope in vWf, different from that
      reacting with 1C1E7. When com-bined, 1C1E7 and 75H4B12 promoted vWf binding to
      isolated GPIb under static conditions, even in the absence of ristocetin or
      botrocetin, and induced platelet aggregation synergistically in the presence of
      zero to subthreshold ristocetin concentrations. Specific inhibitors of GPIbalpha
      vWf interactions prevented vWf binding to GPIbalpha in ELISA and during platelet
      aggregation. In addition, the 1C1E7 dependent platelet aggregation involved Fc
      receptor mediated platelet activation, a phenomenon even more pronounced when
      1C1E7 and 75H4B12 were combined. A 75H4B12 binding phage expressing a peptide
      homologous with vWf sequence 88-95 neutralized the antibody induced platelet
      activation. However, at arterial shear rates, both 1C1E7 and 75H4B12 potently
      prolonged cartridge closure times in the PFA-100, compatible with inhibition of
      platelets by vWf, unfolded by the combined action of shear stress and antibodies.
      CONCLUSIONS: We conclude that antibodies directed against different epitopes in
      the N-terminus of vWf modify the folded vWf structure synergistically and enhance
      A1 domain mediated vWf binding to platelet GPIb at low shear forces. In addition,
      once platelet-bound, IgG antibodies potently activate platelets via the FcgammaII
      receptor. Thus, such antibodies may promote immune mediated thrombosis at low
      shear rates, typical of the venous circulation. In contrast, at arterial shear
      rates, anti-vWf antibodies may rather compromise platelet function following
      enhanced binding of the unfolded vWf multimers to platelets, shielding platelets
      from interacting with subendothelial and soluble ligands.

PMID- 11981109
TI  - In vitro bleeding test with PFA-100-aspects of controlling individual
      acetylsalicylic acid induced platelet inhibition in patients with cardiovascular
      disease.
AB  - OBJECTIVES: This study investigated the usefulness and practicability of a
      platelet function analyzer (PFA-100(TM), DADE-Behring, Germany) to determine
      individual platelet inhibition in patients treated with acetylsalicylic acid
      (ASA). BACKGROUND: Patients with coronary artery disease (CAD) routinely and
      during angioplasty (PTCA) receive standard doses of ASA to avoid acute coronary
      syndromes and abrupt vessel closures without information of the individual
      efficacy of platelet inhibition. METHODS: With the PFA-100(TM) a standardized
      bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is
      aspirated through a capillary ( solidus in circle 200 microm) and through an
      aperture ( solidus in circle 147 microm). The time until occlusion of the
      aperture (closure time, CT) by a stable platelet plug induced by shear stress,
      collagen and epinephrine (COLL/EPI-CT) or shear stress, collagen and adenosine 5'
      diphosphate (COLL/ADP-CT) is determined. To examine the usefulness of the PFA
      100(TM) as a rapid bedside test and the individual effect of ASA, closure time
      was measured in healthy individuals (n=17), in patients with stable CAD (n=19)
      and in patients undergoing PTCA (n=8). RESULTS: Patients with stable CAD and
      regular medication with 100 mg ASA per day for at least 3 month showed shorter
      COLL/ADP-CT in comparison to healthy individuals who took only one single dose of
      100 mg ASA. Of the patients with CAD 63% had a COLL/EPI-CT within normal range
      suggesting a low or no response to ASA. Also only 50% of the patients undergoing
      PTCA reached the expected COLL/EPI-CT>300 s after an additive single dose of 500
      mg ASA intravenously. Neither heparin, phenprocoumon, sex nor different blood
      sampling methods seem to influence the measurements relevantly. CONCLUSIONS: This
      pilot study indicates that with the PFA-100(TM) test device a simple and quick
      measurement of an in vitro bleeding time is possible. It is able to detect an
      increase in the bleeding time after a single dose of ASA 100 mg in healthy
      subjects, reflecting a sensitive detection of ASA induced changes in platelet
      inhibition respective activation. Differences in the individual response to ASA
      could be observed in healthy subjects, patients with stable CAD and patients
      undergoing PTCA. Further studies should validate the PFA-100(TM) with standard
      methods to determine ASA response in patients with cardiovascular disease and
      investigate implications for treatment and outcome in this patient group.

PMID- 11981110
TI  - An analysis of mechanisms underlying the antifibrinolytic properties of
      radiographic contrast agents.
AB  - BACKGROUND: Radiographic contrast agents inhibit fibrinolysis, although by poorly
      defined pathways. The purpose of this study was to define specific mechanisms by
      which contrast agents inhibit clot lysis. METHODS AND RESULTS: Diatrizoate (high
      osmolar ionic agent), ioxaglate (low osmolar ionic), and ioversol (nonionic) were
      studied in vitro. Diatrizoate inhibited clot lysis by 81.3+/-0.6% vs. control
      (p<0.001). Ioxaglate inhibited clot lysis by 41.7+/-11.9%, which was of
      borderline significance (p=0.07). Ioversol did not significantly inhibit clot
      lysis (14.9+/-11.5% decrease vs. control; p>0.3). Inhibition of fibrinolysis was
      not explained by the high osmolarities of contrast agents, by their iodine
      content, or by their effects on the amidolytic activities of t-PA, urokinase, or
      plasmin. However, plasminogen activation by t-PA, urokinase, or streptokinase was
      significantly inhibited by contrast agents. Diatrizoate, ioxaglate, and ioversol
      inhibited plasminogen binding to plasma clots by 51+/-4% (p<0.001), 30.1+/-4%
      (p<0.01), and 19.4+/-7% (p=0.07), respectively. Plasma clots formed in the
      presence of contrast agents were resistant to lysis by plasmin. Diatrizoate
      produced the most potent effect, inhibiting clot lysis by 40+/-5.7% (p<0.03).
      Contrast agents did not inhibit plasminogen binding to fibrin or plasmin-mediated
      fibrinolysis if they were added after clot formation. Contrast agents altered
      clot turbidity, an index of fibrin structure, if present during clot formation,
      but not if added to preformed clots. Contrast agents did not affect plasminogen
      activator inhibitor-1 or alpha(2)-antiplasmin function. CONCLUSIONS: Contrast
      agents inhibit clot lysis by inhibiting plasminogen activation and by disrupting
      interactions of plasminogen and plasmin with fibrin by altering fibrin structure.
      Significant variation in antifibrinolytic properties exists between different
      contrast agents.

PMID- 11981111
TI  - Right atrial thrombus treated successfully with abciximab and heparin.
AB  - We report here a case of right atrial thrombus diagnosed by echocardiography in a
      25-year-old female patient with Hodgkin's disease receiving chemotherapy and
      heparin. After 24 hours therapy with the glycoprotein IIb/IIIa receptor
      antagonist (abciximab) with concomitant heparin the complete dissolution of the
      thrombus could be demonstrated by transesophageal echocardiography. To our
      knowledge this case represents the first use of abciximab in right atrial
      thrombosis.

PMID- 11981112
TI  - Low molecular weight heparin and unfractionated heparin in the early
      pharmacologic management of acute coronary syndromes: a meta-analysis of
      randomized clinical trials.
AB  - BACKGROUND: The standard of care in Acute Coronary Syndromes (ACS) includes a
      full complement of antischemic and antithrombotic therapy. Although aspirin is
      used widely and concomitant anticoagulation is recommended, the comparative
      benefits of low molecular weight heparin (LMWH) and unfractionated heparin (UFH)
      have not been defined. METHODS/RESULTS: A meta-analysis including all randomized
      clinical trials comparing LMWH and UFH for the treatment of non-ST segment
      elevation acute coronary syndromes was performed. Risk ratios (RR), using the
      DerSimonian-Laird Model, were calculated from a total of 13,320 patients. Death
      (RR 0.98, 95% CI 0.73-1.31), death and myocardial infarction (MI) (RR 0.86, 95%
      CI 0.74-1.01), death, MI, recurrent angina or revascularization (RR 0.89, 95% CI
      0.74-1.07) and major hemorrhage (RR 1.01, 95% CI 0.81-1.25) occurred with similar
      frequencies for the anticoagulant-based strategies. CONCLUSIONS: Fixed dose LMWH
      therapy given subcutaneously compares favorably with UFH titrated to a target
      level of anticoagulation and should be considered a safe, effective, and
      clinically acceptable alternative in the early management of patients with non-ST
      segment elevation ACS. The superiority of LMWH preparations characterized by high
      in vitro factor Xa to thrombin inhibitory capacity is supported by clinic trial
      data but requires further investigation.

PMID- 11981113
TI  - Endometrioid carcinoma of the uterine corpus: a review of its pathology with
      emphasis on recent advances and problematic aspects.
AB  - This review considers the pathologic features of endometrioid carcinoma of the
      uterine corpus, which accounts for approximately 80% of endometrial
      adenocarcinomas, with an emphasis on its histologic features, recent advances,
      and problematic aspects. In addition to typical endometrioid carcinoma, the
      variants of endometrioid carcinoma covered include secretory carcinoma,
      villoglandular endometrioid carcinoma, endometrioid carcinoma with small
      nonvillous papillae, endometrioid carcinomas with microglandular and sertoliform
      patterns, and endometrioid carcinomas with metaplastic changes. These changes
      include a variety of different appearances of squamous epithelia (ranging from
      mature and keratinizing to immature with only subtle evidence of a squamous
      nature), clear cells, surface changes resembling syncytial metaplasia or
      microglandular hyperplasia, ciliated cells, oxyphilic cells, and spindled
      epithelial cells (sarcomatoid carcinoma). The last is one of several variants
      that may cause a biphasic appearance, all of which should be distinguished from
      the malignant mullerian mixed tumor. Rare findings in endometrioid carcinomas
      include hyalinization, psammoma bodies, and foci of stromal metaplasia such as
      osteoid. Unusual growth patterns of endometrioid carcinomas include involvement
      of adenomyosis, the "diffusely" infiltrating pattern of myoinvasion, and a
      previously unemphasized pattern of myoinvasion with "pinched off" glands that may
      be cystic or have a pseudovascular appearance, often with a myxoid stromal
      reaction. Other aspects of endometrioid carcinoma discussed are its
      immunoprofile, grading, cervical involvement (including a hitherto undescribed
      "burrowing" pattern of extension within the cervix that can result in
      underdiagnosis of stage IIB disease), carcinoma arising in the lower uterine
      segment, carcinoma arising in polyps and adenomyomas, carcinoma in young women,
      tamoxifen-related carcinoma, associated ovarian endometrioid carcinoma, and
      peritoneal keratin granulomas. Finally, the differential diagnosis of
      endometrioid carcinoma is briefly considered with a section on benign mimics,
      including curettage-related changes, menstrual changes, adenomyosis-related
      problems, metaplastic changes, atypical polypoid adenomyoma, radiation atypia,
      and papillary proliferations, and a section on metastatic colonic carcinoma.

PMID- 11981114
TI  - Molecular and biologic markers of premalignant lesions of human breast.
AB  - There is currently great interest in the detection and characterization of
      putative precursor breast cancer lesions because of the possibility of
      chemoprevention. Knowledge of the biologic features of premalignant lesions,
      although limited, is rapidly evolving. Premalignant breast lesions have been
      examined for the presence of genetic alterations and for the expression of
      biomarkers such as the estrogen receptor (ER), Ki67, p53, and HER2/neu. Data
      obtained from genetic studies of precursor breast lesions clearly support the
      contention that genetic alterations begin quite early in selected subsets of
      histologically benign lesions. Although the results of biomarker expression
      profiles have been contradictory, most studies agree that precursor lesions
      significantly overexpress ER and that progressive alterations in ER expression
      accompany the transition of normal cells to hyperplastic lesions and carcinoma in
      situ. So far, the collected evidence indicates that precursor lesions in the
      breast demonstrate biomarker expression profiles and genetic abnormalities that
      are distinct from those of terminal ductal lobular units but share some of these
      features with invasive tumors. Future research in this field is urgently needed
      to identify specific biomarkers of prognostic and predictive value, which can
      help not only in the selection of patients for chemopreventive therapy but in
      monitoring the progression of high-risk lesions.

PMID- 11981115
TI  - MyoD1 and myogenin expression in human neoplasia: a review and update.
AB  - The MyoD1 family of myogenic nuclear regulatory proteins includes MyoD1/myf3 and
      myogenin/myf4. These genes and their proteins are critical for skeletal muscle
      development. Antibodies to MyoD1 and myogenin are relatively recent additions to
      the armamentarium of the surgical pathologist. This article reviews the biology
      of the myogenic nuclear regulatory proteins and their use in the diagnosis of
      rhabdomyosarcoma. Special attention is given to technical and interpretative
      issues critical to the use of these antibodies in diagnostic pathology.

PMID- 11981117
TI  - Locomotor activity induced by noncompetitive NMDA receptor antagonists versus
      dopamine transporter inhibitors: opposite strain differences in inbred long-sleep
      and short-sleep mice.
AB  - BACKGROUND: The actions of ethanol in the brain involve multiple neuroreceptor
      systems, including glutamatergic N-methyl-D-aspartate receptor (NMDAR) channels.
      In a novel environment, both ethanol and the noncompetitive NMDAR antagonist MK
      801 stimulate locomotor activity to a lesser extent in inbred long-sleep (ILS)
      mice compared with inbred short-sleep (ISS) mice. The behaviorally activating
      effects of noncompetitive NMDAR antagonists are thought to involve increased
      monoamine neurotransmission. Thus, in this study, we sought to determine whether:
      (1) habituation to the behavioral environment alters the differential locomotor
      stimulant effects of noncompetitive NMDAR antagonists in ILS and ISS mice and (2)
      the differential behavioral sensitivity of ILS and ISS mice to noncompetitive
      NMDAR antagonists is mediated through direct inhibition of the dopamine
      transporter (DAT). METHODS: Open field locomotor activity was measured following
      acute systemic injection of saline or drug. [3H]DA uptake parameters were
      determined in striatal synaptosomes prepared from drug-naive mice. RESULTS:
      Habituation to the testing environment abolished the strain differences in saline
      induced locomotor activity. However, ethanol- as well as MK-801-treated ILS mice
      still exhibited reduced locomotor activity compared with ISS mice, suggesting
      that a drug-environment interaction is not the primary explanation for the strain
      differences. The noncompetitive NMDAR antagonists phencyclidine and ketamine also
      induced significantly lower locomotor activity in ILS than in ISS mice. In
      contrast, the DAT inhibitors cocaine and GBR 12909 and the DA releaser
      amphetamine induced greater locomotor activity in ILS than in ISS mice, a strain
      difference opposite that of the noncompetitive NMDAR antagonists. Furthermore,
      the differential behavioral effect found with DAT inhibitors was not mediated by
      differences in the affinity nor number of striatal DATs between ILS and ISS mice.
      CONCLUSIONS: Our results support the conclusion that the differential locomotor
      stimulant effects of ethanol and noncompetitive NMDAR antagonists in ILS and ISS
      mice are not mediated through direct inhibition of DAT.

PMID- 11981118
TI  - Altered emotion-modulated startle in young adults with a family history of
      alcoholism.
AB  - BACKGROUND: Alcoholism risk may be accompanied by poor regulation of emotions,
      signaling altered central nervous system processes. This study used the emotion
      modulated startle paradigm to test the hypothesis that young adults with a
      positive paternal history of alcoholism (FH+), relative to family-history
      negative persons (FH-), have altered emotional reactivity to environmental cues.
      METHODS: We tested 30 FH+ and 30 FH-, 15 males and 15 females in each group.
      Participants completed self-report instruments and interviews and had eye blink
      electromyograms (EMG) measured to acoustic startle probes while viewing color
      photographs rated as affectively pleasant, neutral, and unpleasant. RESULTS: FH-
      had the expected linear increase in startle magnitude, with eye blink EMG gaining
      in strength (F = 18, p < 0.0002) from pleasant to neutral to unpleasant slides.
      In contrast, FH+ did not show EMG potentiation to the unpleasant slides and
      therefore lacked the same linear trend (F < 1, p > 0.4). Notably, FH groups rated
      the emotional valence and arousal of the photographs in similar ways. Self
      reported negative affect partly accounted for the lack of startle potentiation in
      FH+, suggesting that startle modulation differences between the groups may be
      associated with underlying psychological characteristics. CONCLUSIONS: These
      findings implicate altered limbic outputs to the startle pathway in FH+ despite
      normal conscious evaluation of emotional arousal and pleasantness of the slides.
      This method may provide a useful paradigm for testing processing of emotionally
      relevant stimuli in relation to risk for alcohol use disorders.

PMID- 11981119
TI  - The effects of NMDA and GABAA pharmacological manipulations on ethanol
      sensitivity in immature and mature animals.
AB  - BACKGROUND: Sensitivity to the hypnotic effects of ethanol dramatically increases
      with age (Silveri and Spears, 1998). Little is known regarding the neural
      mechanisms that might underlie this relative resistance of young animals to
      ethanol. The present study used a psychopharmacological approach to examine the
      influence of NMDA (N-methyl-D-aspartate) and GABA (gamma-Aminobutyric acid)
      receptor systems in modulating age differences in ethanol responsiveness between
      young [postnatal day (P26)] and mature (P70) female and male Sprague-Dawley rats.
      METHOD: Dose response curves were established for the effects of intraperitoneal
      (ip) administration of the NMDA antagonist (+)MK-801 (0.75, 1.0, or 1.25 mg/kg),
      the GABAA agonist muscimol (0.75, 1.25, or 1.75 mg/kg), or saline on loss and
      regain of the righting reflex and trunk blood alcohol levels following 3.5 g/kg
      of ethanol. RESULTS: (+)MK-801 increased time to regain the righting reflex at
      both ages, maintaining the age-related increase in ethanol sensitivity typically
      observed, although a gender effect also emerged at P70, with females being more
      sensitive than males to (+)MK-801-induced increases in duration of loss of the
      righting reflex. In contrast to the across-age similarity in responsiveness to
      (+)MK-801, P26 animals were considerably more sensitive to muscimol's enhancing
      effect on ethanol sedation than mature animals. CONCLUSION: Although modulation
      of either the NMDA or GABA system enhances the sedative effects of ethanol at
      both ages, stimulation of the GABAA receptor is a more effective means of
      prolonging ethanol sedation in immature than mature animals.

PMID- 11981120
TI  - Free-choice ethanol consumption under the influence of GABAergic drugs in rats.
AB  - BACKGROUND: Neurobiological mechanisms leading from controlled alcohol
      consumption to addiction are poorly understood. Among multiple neurotransmitters
      gamma-amino-butyric acid (GABA) is suggested to play a role. The present
      investigation studied effects of drugs interacting with the GABAergic system on
      the motivation of ethanol consumption. METHODS: Fifty male PVG/OlaHsd rats were
      analyzed for free-choice ethanol drinking behavior without and with pre-exposure
      to drugs acting on the GABAergic system. For pretreatment, animals received the
      benzodiazepine agonists or antagonists diazepam, flumazenil, or Ro15-4513, or the
      GABA uptake inhibitor tiagabine via the drinking water for 4 weeks (day -21 until
      day 7). On day 0, two bottles containing 5% and 12% ethanol were added. On day 7,
      GABAergic drug exposure was discontinued and drug solutions were replaced by
      water. Between days 8 and 35, three alcohol deprivation periods of 1 to 3 days
      were randomly implemented. RESULTS: The animals ingested substantial amounts of
      ethanol that was differentially affected by the GABAergic drugs. Diazepam
      increased and flumazenil decreased ethanol consumption significantly by about
      30%. Without GABAergic drug pretreatment, a significant alcohol deprivation
      effect indicated by enhanced ethanol consumption after re-exposure to alcohol was
      observed after the third deprivation phase. The deprivation effect was prevented
      by pretreatment with diazepam or flumazenil, unaffected by Ro15-4513, and
      advanced by tiagabine. CONCLUSIONS: Modulation of GABAergic neurotransmission
      affects subsequent ethanol consumption and deprivation effects. Because enhancing
      of the GABAergic tone by the GABA uptake inhibitor tiagabine or by the
      benzodiazepine diazepam had different behavioral consequences, it seemed likely
      that the two drugs induce differential adaptive changes leading to distinct
      alterations in the motivation to consume alcohol.

PMID- 11981121
TI  - Testing hypothesized predictors of change in conjoint behavioral alcoholism
      treatment for men.
AB  - BACKGROUND: The model on which alcohol-related Behavioral Couples Therapy (ABCT)
      is based posits three primary domains related to alcohol consumption: individual
      factors, the quality and nature of the spouse's response to alcohol-related
      situations, and the nature and quality of the couple's marital interactions.
      METHODS: This study tested the model underlying ABCT in a sample of 68 male
      alcoholics and their partners, who completed at least five sessions of a 15
      session outpatient treatment study in which they received ABCT. Couples were
      assessed at baseline, during treatment, and for 6 months after treatment
      completion. Stepwise multiple regression was used to test specific predictors
      derived from the ABCT model. RESULTS: Some support was provided for each
      component of the ABCT model. Individual drinker variables predicted drinking
      outcomes, both during and after treatment. Specifically, greater drinking
      severity and drinking frequency at baseline predicted poorer drinking outcomes.
      Older client age and more education predicted less frequent but more intense
      drinking. Spouse coping was related primarily to measures of drinking intensity,
      rather than drinking frequency. Less intense drinking during treatment was
      predicted by greater spousal use of problem solving and social support to deal
      with problems and less use of self-blame, wishful thinking, and avoidance. After
      treatment, however, spouse coping had a less consistent relationship to drinking
      intensity. In the marital domain, drinking during treatment was unrelated to
      pretreatment marital satisfaction measures. However, in the 6 months after
      treatment, men's ability to remain abstinent was predicted by the quality of the
      pretreatment marital relationship, and the intensity of their drinking was
      predicted by the degree of their marital happiness immediately after treatment.
      CONCLUSIONS: Results provided substantial support for the ABCT model,
      particularly in relationship to the role of the spouse in affecting heavy
      drinking.

PMID- 11981122
TI  - Comparison of 3190 alcohol-dependent individuals with and without suicide
      attempts.
AB  - INTRODUCTION: Suicidal behaviors are often seen in alcohol-dependent individuals.
      The aim of this study is to identify and confirm risk factors for suicide
      attempts in a large, family-based sample of alcoholics. METHODS: Semistructured,
      detailed interviews were administered to 3190 alcohol-dependent individuals as
      part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information
      about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity,
      substance use disorders, and characteristics of alcohol dependence were obtained
      from alcohol-dependent probands, controls, and their relatives. RESULTS: As
      determined by both univariate comparison and multivariate logistic regression
      analysis, alcohol-dependent individuals with a history of suicide attempts were
      found to have a significantly more severe course of alcohol dependence and a
      higher prevalence of both independent and substance-induced psychiatric disorders
      and other substance dependence. First-degree relatives of subjects with suicide
      attempts showed a significantly higher rate of suicide attempts, even after
      controlling for additional relevant diagnoses. CONCLUSION: These results support
      the hypothesis that alcohol-dependent individuals with a history of suicide
      attempts are more severely impaired. Screening and subsequent treatment of
      alcohol use disorder, psychiatric comorbidity, and substance use disorders among
      alcoholics may be crucial in preventing suicide attempts and completions.

PMID- 11981123
TI  - Prevention of alcohol-related deaths in middle-aged heavy drinkers.
AB  - BACKGROUND: Alcohol as a cause of death in middle-aged patients is well-known
      from clinical studies. A similarly important correlation in the general
      population of urban middle-aged men is highly underestimated. Health screening
      investigations have shown that mortality related to alcohol is five times more
      common in nonparticipants than in participants. From the mid-70s, the Malmoe
      Screening and Intervention Study (MSIS) commenced screening investigations
      including a large number of residents of Malmoe. One goal was to find
      intervention programs for individuals in an early development of problem
      drinking, thereby preventing development of serious complications of endstage
      alcoholism. Herein, we report on the mortality of heavy drinkers (drinking more
      than 40 g alcohol/day) who were randomized to an intervention or control
      procedure and whose median survival was 13 years postentry into the MSIS.
      METHODS: Health-screened men, aged 45-49 years at the initial screening
      examination and displaying serum gamma-glutamyltransferase (GT) in the top
      decentile of the GT distribution, were included. A total of 978 out of 11,257
      participants met this criteria. A randomized intervention and control study was
      performed for four years and consisted of men (n = 667) who were born between
      1927-1937 and who had two consecutive high GT values within 3 weeks along with
      heavy alcohol consumption. Half the individuals were informed of the test results
      and invited for further assessment by a senior physician (n = 365). The
      principles for brief intervention (DiClemente et al.,1991; Miller and Sanchez,
      1993; National Institute of Alcohol Abuse and Alcoholism, 1999) were applied. The
      other half of the men (n = 302) were left with the information that they had a
      high GT value and were followed up with laboratory checkups every 2nd year.
      Mortality was followed up until 1991 and information on deaths was obtained from
      hospital and police records, necropsy reports, and death certificates. RESULTS:
      Long-term follow-up of mortality for 10-16 years (median, 13 years) showed that
      124 of the 978 men had died (12.7%). Autopsy was performed in 96.5% of the cases.
      In 59 men (48%), death was alcohol-related. In the intervention group (n = 365),
      38 (10.4%) men were dead and in the control group (n = 302), 42 (13.9%) men had
      died. There was a statistically significant difference (p = 0.026), with
      advantage for treatment. Less alcohol-related deaths and deaths occurring later
      during follow-up were found in the intervention group compared with the control
      group. The difference between the groups in total mortality, coronary heart
      disease, and cancer death was not statistically significant. CONCLUSIONS: These
      findings support previous results from the MSIS study indicating that long-term
      intervention in urban males with alcohol-induced GT increases may be beneficial
      in terms of survival.

PMID- 11981124
TI  - Concurrent and discriminant validity of DSM-IV symptoms of impaired control over
      alcohol consumption in adolescents.
AB  - BACKGROUND: Little research has examined impaired control over alcohol
      consumption in adolescents. This study examined the concurrent and discriminant
      validity of two DSM-IV dependence criteria that reflect impaired control over
      drinking: "using more or longer than intended" (Larger/Longer) and "persistent
      desire or unsuccessful efforts to quit or cut down" (Quit/Cut Down). METHODS:
      Adolescent drinkers, ages 13-19 (N = 173), were recruited from addictions
      treatment (76%) and community sources (24%). A modified SCID that included
      assessment of alcohol craving and questionnaires measuring dependence severity,
      attempts to limit drinking, and impulsivity were administered. RESULTS:
      Larger/Longer had higher prevalence and an earlier onset than Quit/Cut Down,
      suggesting that the symptoms respectively represent milder and more severe
      manifestations of impaired control over drinking. Both symptoms were associated
      with drinking frequency, dependence severity, episodes of passing out, and an
      independent measure of unsuccessful attempts to limit drinking. Alcohol craving
      was associated with both Larger/Longer and Quit/Cut Down. Impulsivity was
      correlated with Larger/Longer but not Quit/Cut Down. CONCLUSIONS: Larger/Longer
      and Quit/Cut Down demonstrated adequate concurrent validity. The two symptoms
      were distinguished by severity and differential relations with impulsivity,
      suggesting that Larger/Longer and Quit/Cut Down reflect different types of
      impaired control over alcohol consumption. Results suggest the need for improved
      description and scaling of the impaired control construct in adolescents.

PMID- 11981125
TI  - Alcohol-related problems, drug use, and male intimate partner violence severity
      among US couples.
AB  - BACKGROUND: Particularly for women, level of intimate partner violence (IPV)
      severity is associated with risk of injury. Previous research suggests that male
      drinking problems and drug use are key risk factors. Few studies, however, have
      examined the associations between male and female alcohol problems and drug use
      and risk of moderate and severe male IPV in general household population samples.
      METHODS: A multiethnic sample of 1615 married and cohabiting couples was obtained
      from the 1995 National Study of Couples, a cross-sectional study on alcohol and
      IPV. We assessed the contribution of past year male and female alcohol-related
      problems (i.e., drinking consequences and alcohol-dependence symptoms) and
      illicit drug use to the risk of moderate and severe male IPV. A series of
      generalized multinomial logit models, with adjustment for sociodemographic and
      psychosocial covariates, was constructed to assess these associations. RESULTS:
      Female and male alcohol-related problems and female drug use, were associated
      with increased risk of moderate and severe male IPV. Contrary to our expectation,
      male drug use was not associated with elevated risk for either type of male IPV.
      Compared with couples residing in low-unemployment neighborhoods, couples
      residing in high-unemployment neighborhoods were at greater risk for severe, but
      not moderate, male IPV. CONCLUSIONS: Alcohol-related problems among men and women
      and drug use among women, appear to be important correlates of male IPV severity
      among couples in the general population. These findings can aid in IPV screening
      efforts, the formulation of prevention strategies, and help inform batterer and
      victim treatment programs.

PMID- 11981126
TI  - Changes in serum apolipoprotein and lipoprotein profile after alcohol withdrawal:
      effect of apolipoprotein E polymorphism.
AB  - BACKGROUND: Apolipoprotein (Apo) E genotype and alcohol consumption or withdrawal
      strongly affect lipoprotein (Lp) metabolism and, as with any genetic and
      environmental factors, they might interact. The aim of this study was to
      investigate this gene/environment interaction by analyzing the effect of the apoE
      genotype on the alcohol withdrawal-induced alterations in the serum Apo and Lp
      profile. METHODS: ApoE genotypes and concentrations of serum cholesterol,
      triglyceride, and Lps containing apoA-I, A-II, B, E, and C-III were determined in
      84 male alcohol abusers before and after 3 weeks of abstinence. RESULTS: After
      withdrawal, concentrations of serum apoA-I, LpA-I, LpA-I/A-II, apoC-III, LpC-III
      non-B, apoE, and LpE-non-B significantly decreased, whereas those of
      triglycerides and apoB increased; levels of cholesterol, LpC-III:B, and LpB:E
      were not affected. ANOVA shows that apoE polymorphism effects were quite similar
      before and after alcohol withdrawal on all serum Apos and Lps (the interaction
      term between withdrawal and apoE genotype was not significant). The only
      interaction term that was borderline significant (p < or = 0.10) concerned the
      apoB concentration. Before withdrawal, no association between apoB level and apoE
      polymorphism was observed, whereas after abstinence, a borderline significant (p
      < or = 0.10) gradient of concentration across the three groups of subjects
      (epsilon2 carriers < epsilon3/epsilon3 < epsilon4 carriers) was noticed.
      CONCLUSIONS: Alcohol abstinence causes major changes in the antiatherogenic Apos
      and Lps and may increase those known to be atherogenic. Heavy alcohol consumption
      seems to alter the effect of apoE polymorphism on apoB levels, and further
      investigations are needed to clarify the mechanisms involved in this phenomenon:
      a defect in sialylation of apoE, formation of acetaldehyde adducts on apoB, or
      both.

PMID- 11981127
TI  - Fracture healing and bone mass in rats fed on liquid diet containing ethanol.
AB  - BACKGROUND: Studies in animal models for alcohol abuse have suggested that
      ethanol inhibits bone growth, decreases bone formation, and increases fracture
      risk. METHODS: Experimental tibia fracture healing in rats fed a liquid diet
      containing 7.2% ethanol for 8 weeks was investigated with histological and
      osteodensitometric studies with respect to the control group. After 4 weeks of
      vitamin A- and sucrose-enriched milk containing 7.2% ethanol feeding, we created
      closed tibia fractures, which were then fixed with intramedullary nails, in 10
      rats. After a follow-up time of 4 weeks, the rats were killed for examination.
      The same procedure was performed in another 10 rats, which were fed on the same
      diet (isocaloric modified liquid diet) but without ethanol and used as the
      control group. A histological scoring system was developed for fracture healing.
      RESULTS: Histological evaluation of fracture region revealed an average fracture
      healing score of 1.9 in the ethanol-fed group versus 2.6 in the control group (p
      = 0.014). In the test group, dual-energy x-ray absorptiometry measurements in the
      fracture region showed a mean bone mineral density of 0.11 +/- 0.03 g/cm(2),
      whereas it was 0.130 +/- 0.051 g/cm(2) in the control group (p = 0.000). The mean
      bone mineral content in the fracture region was 0.103 +/- 0.08 g/cm(3) in the
      test group versus 0.128 +/- 0.06 g/cm(3) in the control group (p = 0.000). A
      significant correlation was found among histological scores, bone mineral density
      (r = 0.64, p = 0.04), and bone mineral content (r = 0.63, p = 0.04). CONCLUSIONS:
      This study showed that rats fed on a diet mixed with ethanol have a
      histologically delayed fracture healing associated with decreased bone density
      and mineral content. Besides the negative effects of ethanol on bone metabolism,
      it also interferes with the fracture-healing process.

PMID- 11981128
TI  - Phosphatidylethanol in rat organs after ethanol exposure.
AB  - BACKGROUND: Phosphatidylethanol (PEth) is an abnormal phospholipid formed in
      mammalian cells that have been exposed to ethanol. It has been suggested that
      PEth mediates some of the damaging effects of ethanol on cells. This study was
      performed to investigate the level of PEth in organs of rats after in vivo
      alcohol exposure. METHODS: Three exposure models were studied: (1) acute,
      intraperitoneal injection of ethanol (n = 3 x 3); (2) chronic, forced ethanol
      drinking (n = 6); and (3) chronic, free choice of ethanol (n = 20). PEth was
      analyzed by high-performance liquid chromatography after lipid extraction of the
      organs. RESULTS: One acute injection gave detectable PEth levels in most organs
      analyzed, with maximal levels reached after 2 hr. The highest levels were reached
      in intestines, stomach, and lung. No PEth was detected in skeletal muscle,
      pancreas, or testis. The two exposure models for oral intake of ethanol also gave
      detectable PEth levels in most organs. The highest levels were reached in
      stomach, lung, and spleen. PEth was detected in muscle only in animals with heavy
      total alcohol intake. CONCLUSIONS: PEth is formed in most organs of rats exposed
      to ethanol acutely or chronically. Variations in PEth level and rates of PEth
      formation and PEth degradation are organ specific.

PMID- 11981129
TI  - Interleukin-4 treatment restores cellular immunity after ethanol exposure and
      burn injury.
AB  - BACKGROUND: Previous studies from this laboratory showed that the suppression of
      cell-mediated immunity after the combined injury of ethanol exposure and burn is
      mediated by increased presence of the proinflammatory cytokine interleukin (IL)
      6. IL-4 is a T-helper cell type 2 lymphocyte-derived cytokine that serves to down
      regulate the inflammatory response. Therefore, the goal of this study was to
      evaluate the effects of ethanol exposure and burn injury on lymphocyte production
      of IL-4 and to determine whether administration of IL-4 could improve cellular
      immunity after ethanol exposure and burn injury through modulation of IL-6
      levels. METHODS: Mice were subjected to a 15% total body-surface area burn (or
      sham) injury 30 min after being given a single dose of alcohol (or saline)
      designed to achieve a blood alcohol level of 100 mg/dl. Thirty minutes after
      burn, mice were treated with IL-4 (or vehicle) and were killed 24 hr later.
      RESULTS: Lymphocytes from ethanol/burn mice secreted significantly less IL-4 in
      comparison to all other groups of mice (p < 0.05). Administration of IL-4
      resulted in a complete restoration of the delayed-type hypersensitivity (p <
      0.01) and splenocyte proliferative responses (p < 0.05) and a significant
      reduction in circulating and splenic macrophage-derived IL-6 (p < 0.05). Addition
      of IL-4 (100 or 300 pg/ml) to cultures generated from ethanol/burn and vehicle
      mice resulted in a complete restoration of splenocyte proliferation and a
      concomitant attenuation of macrophage IL-6 production. CONCLUSIONS: These studies
      suggest that the loss of lymphocyte production of IL-4 after ethanol exposure and
      burn injury may contribute to the exaggerated production of IL-6, a known
      mediator of immune suppression after injury. Moreover, the administration of IL-4
      may be beneficial for patients with injuries that are characterized by a
      dysregulated inflammatory response.

PMID- 11981130
TI  - Effects of in vitro ethanol on tumor necrosis factor-alpha production by blood
      obtained from simian immunodeficiency virus-infected rhesus macaques.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), a product of monocytes and
      macrophages, functions as an important proinflammatory cytokine in the host's
      response to invading pathogens. METHODS: Because both alcohol abuse and human
      immunodeficiency virus infection affect TNF-alpha production and are known to
      frequently coexist, this study examined the effects of simian immunodeficiency
      virus (SIV) infection and in vitro alcohol exposure on the lipopolysaccharide
      (LPS)-induced TNF-alpha response in blood obtained from SIV-negative and 
      positive animals at the asymptomatic and terminal stages of infection. RESULTS:
      Spontaneous TNF-alpha production was undetectable or low in all groups examined.
      LPS-induced TNF-alpha production was increased in blood obtained at the
      asymptomatic (746 +/- 226 pg/ml) and terminal (1945 +/- 1013 pg/ml) stages,
      compared with that from SIV-negative animals (210 +/- 28 pg/ml), whereas TNF
      alpha messenger RNA content did not differ in LPS-stimulated blood obtained from
      SIV-negative, asymptomatic SIV-positive, or terminal SIV-positive animals.
      Ethanol treatment suppressed TNF-alpha protein production in all groups, whereas
      TNF-alpha messenger RNA levels remained unchanged in blood obtained from animals
      not infected with SIV. CONCLUSIONS: Blood cellular elements remain responsive to
      LPS stimulation with respect to TNF production even into the acquired
      immunodeficiency syndrome stage of SIV disease. However, intoxicating doses of
      alcohol suppress this response, and this may contribute to the immunocompromised
      state of the host.

PMID- 11981131
TI  - Chronic daily ethanol and withdrawal: 3. Forebrain pro-opiomelanocortin gene
      expression and implications for dependence, relapse, and deprivation effect.
AB  - BACKGROUND: Although forebrain pro-opiomelanocortin (POMC)-producing neurons seem
      to mediate or modulate many responses to ethanol consumption, changes in activity
      of this opiomelanocortinergic system in response to chronic ethanol consumption,
      withdrawal, and subsequent abstinence remain unresolved. METHODS: We investigated
      the effects of chronic daily ethanol consumption, withdrawal, and subsequent
      abstinence on adult male Sprague-Dawley rat forebrain opiomelanocortinergic
      activity as reflected by changes in hypothalamic POMC messenger RNA (mRNA)
      content by using a well characterized liquid diet model that we have previously
      demonstrated to accurately simulate not only daily oral ethanol consumption
      quantity and pattern, but also both neuroendocrine and behavioral changes
      characteristic of actively drinking and subsequently abstinent alcoholics.
      RESULTS: After 7 weeks of daily ethanol consumption at night and withdrawal
      during the day, evening mediobasal hypothalamus POMC mRNA concentrations were
      suppressed versus both ad libitum-fed and pair-fed controls. Morning POMC mRNA
      concentrations were also suppressed versus ad libitum-fed controls and tended to
      be decreased versus pair-fed controls. Three weeks after gradual removal of
      ethanol from the diet, mediobasal hypothalamus POMC mRNA concentrations were
      increased relative to ad libitum-fed and pair-fed controls. Plasma concentrations
      of corticosterone, testosterone, and leptin were also altered by the daily
      ethanol/withdrawal treatment and by subsequent abstinence. CONCLUSIONS: Because
      each of these hormones has been demonstrated to modify forebrain POMC gene
      expression under some conditions, the overall changes in forebrain
      opiomelanocortinergic regulation in response to chronic daily ethanol/withdrawal
      and subsequent abstinence probably reflect, at least in part, regulation by
      multiple endocrine mechanisms, together with responses to stress, development of
      tolerance during chronic daily ethanol consumption, and rebound of function after
      termination of this consumption. Overall, the demonstrated changes in forebrain
      POMC gene expression are consistent with significant roles for forebrain
      opiomelanocortinergic regulation in mediating alcohol dependence, propensity to
      relapse, and the alcohol deprivation effect.

PMID- 11981132
TI  - Binge ethanol exposure in adult rats causes necrotic cell death.
AB  - BACKGROUND: Although alcoholics show neurodegeneration after decades of drinking,
      recent studies with an animal model of binge drinking have found corticolimbic
      damage after as few as four days. Neurodegeneration can occur through apoptotic
      or necrotic mechanisms. The goal of this research is to characterize the time
      course of binge ethanol-induced neurodegeneration and to identify apoptotic or
      necrotic characteristics of this neurodegeneration. METHODS: Histologic methods
      (e.g., amino cupric silver staining, Fluoro-Jade B, hematoxylin and eosin,
      transmission electron microscopy) were used to quantify the time course of
      degeneration and to characterize the ultrastructural changes that occur with
      binge ethanol-induced neurodegeneration. RESULTS: After 2 days of binge ethanol,
      significant damage was evident in the olfactory bulb. After 4 days of binge
      ethanol, there was significant damage in the agranular insular cortex, anterior
      piriform cortex, perirhinal cortex, lateral entorhinal cortex, and the temporal
      dentate gyrus. Ultrastructural examination revealed shrunken soma, vacuolated
      cytoplasm, pyknotic nucleus, and irregularly clumped chromatin consistent with
      dark cell degeneration, a form of necrotic neuronal death. CONCLUSIONS: Binge
      drinking causes necrotic neurodegeneration after 2 days of exposure and increased
      damage after 4 days but does not increase during withdrawal. These studies
      indicate that binge drinking induced neurodegeneration is necrotic and occurs
      during ethanol intoxication and not as a result of ethanol withdrawal.

PMID- 11981133
TI  - Cortical gray matter loss in treatment-naive alcohol dependent individuals.
AB  - BACKGROUND: Most studies of the impact of alcohol dependence on the brain have
      examined individuals in treatment. Such samples represent a small proportion of
      alcoholics in the general population. Such samples may embody a bias (Berkson's
      fallacy) if the association between variables (for example, alcoholism and
      cortical gray matter loss) differs between the population of alcoholics in
      treatment and alcoholics in the general population. Our objective was to
      determine if treatment-naive alcoholics show structural brain changes versus
      controls and to compare our findings with reports evaluating alcoholic samples
      drawn from treatment populations. METHODS: Structural MRI was used to assess
      whole brain and regional volumes of cortical gray matter and white matter in 24
      young to middle-aged treatment-naive alcohol-dependent males versus 17 controls.
      RESULTS: Cortical gray matter volumes in alcohol-dependent individuals were
      negatively associated with age and lifetime duration of alcohol use (which were
      highly confounded). These subjects showed reduced whole brain (p < 0.05),
      prefrontal (p < 0.01), and parietal (p < 0.05) cortical gray matter compared with
      controls. White matter and temporal cortex, tissues that usually show volume
      reductions in samples drawn from treatment, did not differ between treatment
      naive alcoholics and controls (all p > 0.40). CONCLUSIONS: Our findings are
      consistent with the hypothesis that structural brain changes in treatment-naive
      alcoholics are less severe than those reported in clinical samples of alcoholics,
      perhaps due to less concomitant psychopathology and a reduced severity of
      alcoholism in treatment-naive alcoholics. However, caution must be taken when
      comparing our findings with results from clinical samples, as we did not directly
      compare treatment-naive alcoholics with treated alcoholics and our treatment
      naive sample tended to be younger than the (clinical) samples reported in the
      literature. Nevertheless, we suggest that most of the reports of the central
      nervous system consequences of alcoholism may not accurately describe the
      majority of alcoholic-dependent individuals.

PMID- 11981134
TI  - Ethanol, endocannabinoids, and the cannabinoidergic signaling system.
AB  - This article represents the proceedings of a symposium at the 2001 annual meeting
      of the Research Society on Alcoholism in Montreal, Canada. The chairpersons were
      Appa Hungund and George Koob. The presentations were (1) Role of endocannabinoids
      in ethanol tolerance, by Appa Hungund; (2) Modulation of cannabinoid receptor and
      its signal transduction in chronic alcoholism, by B. S. Basavarajappa; (3)
      Endocannabinoid involvement in the control of appetitive behavior, by George
      Kunos; (4) Regulation of voluntary ethanol intake by cannabinoid receptor
      agonists and antagonists in alcohol-preferring sP rats, by Giancarlo Colombo; (5)
      Role of endogenous cannabinoid system in alcoholism, by Fernado Rodriguez de
      Fonseca; and (6) Endocannabinoids and dopamine interactions in vivo, by Loren
      Parsons and George Koob.

PMID- 11981135
TI  - How does alcohol contribute to sexual assault? Explanations from laboratory and
      survey data.
AB  - This article summarizes the proceedings of a symposium of the 2001 RSA Meeting in
      Montreal, Canada. The chair was Antonia Abbey and the organizers were Tina
      Zawacki and Philip O. Buck. There were four presentations and a discussant. The
      first presentation was made by Maria Testa whose interviews with sexual assault
      victims suggest that there may be differences in the characteristics of sexual
      assaults in which both the victim and perpetrator were using substances as
      compared to when only the perpetrator was using substances. The second
      presentation was made by Tina Zawacki whose research found that perpetrators of
      sexual assaults that involved alcohol were in most ways similar to perpetrators
      of sexual assaults that did not involve alcohol, although they differed on
      impulsivity and several alcohol measures. The third presentation was made by
      Kathleen Parks who described how alcohol consumption affected women's responses
      to a male confederate's behavior in a simulated bar setting. The fourth
      presentation was made by Jeanette Norris who found that alcohol and expectancies
      affected men's self-reported likelihood of acting like a hypothetical sexually
      aggressive man. Susan E. Martin discussed the implications of these studies and
      made suggestions for future research.

PMID- 11981136
TI  - Gene and antisense delivery in alcoholism research.
AB  - This article represents the proceedings of a symposium at the 2001 annual meeting
      of the Research Society on Alcoholism in Montreal, Canada. Drs. Yedy Israel and
      Fulton Crews were organizers and co-chairpersons. The presentations were (1)
      Introduction to the symposium, by Yedy Israel; (2) Gene delivery to the brain, by
      Fulton T. Crews; (3) Gene therapy in alcoholic liver injury, by Ronald Thurman;
      and (4) Antisense oligonucleotides and antisense-gene delivery, by Yedy Israel.

PMID- 11981137
TI  - Potential neuroprotective effects of acamprosate.
AB  - This article represents the proceedings of a symposium at the 2001 RSA Meeting in
      Montreal, Canada. The organizers were Barbara J. Mason and George F. Koob. Anita
      M. Goodman served as chair. The presentations were (1) Acamprosate inhibits
      alcohol withdrawal-induced neurotoxicity in organotypic hippocampal cultures, by
      John Littleton; (2) Acamprosate alteration of NMDA receptor-dependent synaptic
      transmission and synaptic plasticity, by George R. Siggins; (3) Acamprosate and
      glutamate during ethanol withdrawal, by Philippe De Witte; (4) Clinical evidence
      of protective CNS effects of acamprosate in alcohol-dependent individuals, by
      Barbara J. Mason.

PMID- 11981139
TI  - Perioperative risk: how can we study the influence of provider characteristics?

PMID- 11981140
TI  - Platelets, perioperative hemostasis, and anesthesia.

PMID- 11981141
TI  - Anesthesiologist board certification and patient outcomes.
AB  - BACKGROUND: Board certification is often used as a surrogate indicator of
      provider competence, although few outcome studies have demonstrated its validity.
      The aim of this study was to compare the outcomes of patients who underwent
      surgical procedures under the care of an anesthesiologist with or without board
      certification. METHODS: Medicare claims records for 144,883 patients in
      Pennsylvania who underwent general surgical or orthopedic procedures between 1991
      and 1994 were used to determine provider-specific outcome rates adjusted to
      account for patient severity and case mix, and hospital characteristics. Outcomes
      of 8,894 cases involving midcareer anesthesiologists, 11-25 yr from medical
      school graduation, who lacked board certification were compared with all other
      cases. Midcareer anesthesiologist cases were studied because this group had
      sufficient time to become certified during an era when obtaining certification
      was already considered important, and consequently had the highest rate of board
      certification. Mortality within 30 days of admission and the failure-to-rescue
      rate (defined as the rate of death after an in-hospital complication) were the
      two primary outcome measures. RESULTS: Adjusted odds ratios for death and failure
      to rescue were greater when care was delivered by noncertified midcareer
      anesthesiologists (death = 1.13 [95% confidence interval, 1.00, 1.26], P < 0.04;
      failure to rescue = 1.13 [95% confidence interval, 1.01, 1.27], P < 0.04).
      Adjusting for international medical school graduates did not change these
      results. CONCLUSIONS: When anesthesiology board certification is very common, as
      in midcareer practitioners, the lack of board certification is associated with
      worse outcomes. However, the poor outcomes associated with noncertified providers
      may be a result of the hospitals at which they practice and not necessarily their
      manner of practice.

PMID- 11981142
TI  - Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic
      neuralgia: efficacy and dose-response trials.
AB  - BACKGROUND: There are few repeated dose-controlled trials of N-methyl-d-aspartate
      glutamate receptor antagonists in patients with neuropathic pain. The authors
      sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a
      novel two-stage design. METHODS: The authors studied patients with painful
      diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover
      trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo
      [lorazepam]) and (2) dose-response trial of the preferred active drug in
      responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's
      maximally tolerated dose). Pain intensity was measured on a 20-point scale.
      RESULTS: Nineteen of 23 DN patients and 17 of 21 PHN patients completed the
      efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day
      dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam.
      In the efficacy trial, among patients with DN, dextromethorphan reduced pain
      intensity by a mean of 33% from baseline, memantine reduced pain intensity by a
      mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the
      proportions of subjects achieving greater than moderate pain relief were 68% with
      dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in
      pain intensity in patients with PHN were 6% with dextromethorphan, 2% with
      memantine, and 0% with lorazepam. No comparison with placebo reached statistical
      significance in the efficacy trial. In the 10 DN subjects who responded to
      dextromethorphan, there was a significant dose-response effect on pain intensity
      (P = 0.035), with the highest dose significantly better than that of lorazepam (P
      = 0.03). CONCLUSIONS: Dextromethorphan is effective in a dose-related fashion in
      selected patients with DN. This was not true of PHN, suggesting a difference in
      pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate
      receptors are warranted.

PMID- 11981143
TI  - Pharmacokinetics of bupivacaine during postoperative epidural infusion:
      enantioselectivity and role of protein binding.
AB  - BACKGROUND: Changing plasma protein concentrations may affect the protein binding
      and pharmacokinetics of drugs in the postoperative period. This study examined
      the effect of postoperative increases (in response to surgery) in plasma alpha1
      acid-glycoprotein (AAG) concentrations on the plasma concentrations of the
      enantiomers of bupivacaine during continuous epidural infusion of racemic
      bupivacaine for postoperative pain relief. METHODS: Six patients scheduled for
      total hip surgery with combined epidural and general anesthesia received a bolus
      dose of bupivacaine (65 mg) followed by constant-rate (8 ml/h) epidural infusion
      of 2.5 mg/ml bupivacaine for 48 h. Total and unbound plasma concentrations of the
      enantiomers of bupivacaine and plasma AAG concentrations during the 48-h epidural
      infusion were determined. RESULTS: Total plasma concentrations of the enantiomers
      of bupivacaine increased steadily during the infusion (P < 0.0001), whereas
      unbound concentrations did not change after 12 h (P > 0.1). Total plasma
      concentrations of S(-)-bupivacaine were higher than those of R(+)-bupivacaine (P
      < 0.02), whereas unbound concentrations of S(-)-bupivacaine were lower than those
      of R(+)-bupivacaine (P < 0.002). AAG concentrations initially decreased, but
      thereafter increased steadily (P < 0.0001). Consequently, free fractions of the
      enantiomers initially increased and then decreased with time (P = 0.0002). Free
      fractions of S(-)-bupivacaine were smaller than those of R(+)-bupivacaine (P =
      0.0003). CONCLUSIONS: The study confirmed that the pharmacokinetics of
      bupivacaine are enantioselective. During postoperative epidural infusion,
      changing plasma AAG concentrations affect the protein binding of both enantiomers
      of bupivacaine. Consequently, total plasma concentrations of the enantiomers
      increase with time, whereas unbound concentrations reach a plateau.

PMID- 11981144
TI  - A comparison of intrathecal fentanyl and sufentanil for labor analgesia.
AB  - BACKGROUND: The use of intrathecal opioids for labor analgesia continues to gain
      popularity, but there are limited data to guide this use. Previously, the authors
      established the ED50 for 60 min of labor analgesia from intrathecal sufentanil
      using an up-down sequential allocation study design. The current study first
      establishes an ED50 for intrathecal fentanyl using this same study design to
      establish an intrathecal potency ratio for fentanyl and sufentanil and then uses
      this ratio to compare the efficacy, duration of analgesia, and side effects from
      comparable doses of intrathecal fentanyl and sufentanil. METHODS: Seventy-five
      healthy nulliparous women requesting labor analgesia were enrolled in this two
      part study. In phase I, 20 women received varying doses of fentanyl to establish
      an ED50 for 60 min of labor analgesia. In phase II, 55 women were randomized to
      receive either 36 microg intrathecal fentanyl or 8 microg sufentanil (2 times the
      ED50s) via a combined spinal-epidural technique and by double-blinded design.
      Pain relief, side effects, block height, maternal hemodynamics, and fetal heart
      rate were assessed throughout the study. The duration of spinal analgesia was
      considered to be the time from injection of study drug to the time of the
      patient's first request for additional analgesia. RESULTS: The ED50 of
      intrathecal fentanyl for 60 min of labor analgesia was found to be 18.2 microg,
      and therefore, the potency ratio of intrathecal sufentanil to intrathecal
      fentanyl at the ED50 level is 4.4:1. The duration of spinal analgesia was
      significantly longer from 8 microg intrathecal sufentanil than from 36 microg
      intrathecal fentanyl (104 +/- 34 vs. 79 +/- 34 min, P = 0.009). Otherwise,
      patient demographics, maternal hemodynamics, duration of labor, mode of delivery,
      motor block, subjective leg weakness, pruritus, nausea, pinprick sensory levels,
      visual analog scale pain scores, fetal bradycardia, and Apgar scores were similar
      between groups. CONCLUSION: The relative potency of intrathecal sufentanil to
      fentanyl for labor analgesia is 4.4:1. When using intrathecal opioids alone for
      early labor analgesia, 8 microg sufentanil produces labor analgesia lasting
      approximately 25 min longer than from 36 microg fentanyl, without a statistically
      significant increase in side effects. However, when making a choice between
      fentanyl and sufentanil, one must consider other important factors, such as the
      higher cost of sufentanil and the greater risk of dosing error due to the higher
      potency of sufentanil compared with fentanyl.

PMID- 11981145
TI  - The influence of cuff volume and anatomic location on pharyngeal, esophageal, and
      tracheal mucosal pressures with the esophageal tracheal combitube.
AB  - BACKGROUND: The authors determined the influence of cuff volume and anatomic
      location on pharyngeal, esophageal, and tracheal mucosal pressures for the
      esophageal tracheal combitube. METHODS: Twenty fresh cadavers were studied.
      Microchip sensors were attached to the anterior, lateral, and posterior surfaces
      of the distal and proximal cuffs of the small adult esophageal tracheal
      combitube. Mucosal pressure for the proximal cuff in the pharynx was measured at
      0- to 100-ml cuff volume in 10-ml increments, and for the distal cuff in the
      esophagus and trachea were measured at 0- to 20-ml cuff volume in 2-ml
      increments. The proximal cuff volume to form an oropharyngeal seal of 30 cm H2O
      was determined. In addition, mucosal pressures for the proximal cuff in the
      pharynx were measured in four awake volunteers with topical anesthesia. RESULTS:
      There was an increase in mucosal pressure in the trachea, esophagus, and pharynx
      at all cuff locations with increasing volume (all: P < 0.001). Pharyngeal mucosal
      pressures were highest posteriorly (50-ml cuff volume: 99 +/- 62 cm H2O; 100-ml
      cuff volume: 255 +/- 161 cm H2O). Esophageal mucosal pressures were highest
      posteriorly (10-ml cuff volume: 108 +/- 55 cm H2O; 20-ml cuff volume: 269 +/- 133
      cm H2O). Tracheal mucosal pressures were highest anteriorly (10-ml cuff volume:
      98 +/- 53 cm H2O; 20-ml cuff volume: 236 +/- 139 cm H2O). The proximal cuff
      volume to obtain an oropharyngeal seal of 30 cm H2O was 47 +/- 12 ml. Pharyngeal
      mucosal pressures were similar for cadavers and awake volunteers. CONCLUSION: We
      conclude that mucosal pressures for the esophageal tracheal combitube increase
      with cuff volume, are highest where the cuff is adjacent to rigid anatomic
      structures, and potentially exceed mucosal perfusion pressure even when cuff
      volumes are limited to achieving an oropharyngeal seal of 30 cm H2O.

PMID- 11981146
TI  - Neutrophil adhesion molecule expression and serum concentration of soluble
      adhesion molecules during and after pediatric cardiovascular surgery with or
      without cardiopulmonary bypass.
AB  - BACKGROUND: Increased neutrophil activation by cardiopulmonary bypass (CPB)
      during cardiovascular surgery is thought to be responsible for postoperative
      complications. In children, the contribution of cardiovascular surgery alone to
      this response is not well-characterized. METHODS: Children undergoing surgery
      with CPB (CPB group, n = 35) and without CPB (control, n = 22) were studied (age,
      3-17 yr). Blood was drawn 24 h preoperatively before medication, after
      anesthesia, after connection to CPB, at reperfusion, 4 h to 2 days after surgery,
      at discharge, and months after surgery. Neutrophil antigen expression and serum
      concentration of adhesion molecules, interleukin 8, and C5a (fragment of C5
      complement) were analyzed by flow cytometry and enzyme-linked immunosorbent
      assay, respectively. RESULTS: With and without CPB, anesthesia and surgery
      induced decreased LFA-1 (CD11a-CD18), Mac-1 (CD11b-CD18), CD45, and CD54
      (intercellular adhesion molecule 1) surface expression and sICAM-1 serum
      concentrations (all P < 0.001). sL-selectin serum concentration decreased with
      CPB (P < 0.001) but was not significantly altered in the control. In contrast,
      CD62L expression increased during CPB (P < 0.001). The time course of all
      analyzed markers was not significantly different between CPB and control, with
      the exception of sL-selectin (P = 0.017). One-day preoperative baseline values
      were reached days to months after surgery. Interleukin 8 and C5a serum
      concentrations increased after surgery in both the CPB group and the control
      group. CONCLUSIONS: Pediatric cardiovascular surgery leads to reduced
      adhesiveness and activity of circulating neutrophils. This reduction is more
      pronounced and sustained with CPB. These data may be useful in the assessment of
      novel therapeutic strategies.

PMID- 11981147
TI  - Clevidipine in adult cardiac surgical patients: a dose-finding study.
AB  - BACKGROUND: Treatment of elevated blood pressure is frequently necessary after
      cardiac surgery to minimize postoperative bleeding and to attenuate afterload
      changes associated with hypertension. The purpose of this study was to
      investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium
      channel antagonist, clevidipine, in the treatment of hypertension in
      postoperative cardiac surgical patients. METHODS: Postoperative cardiac surgical
      patients were randomized to receive placebo or one of six doses of clevidipine.
      Hemodynamic parameters were recorded and blood samples were drawn for
      determination of clevidipine plasma concentrations during infusion and after
      discontinuation of clevidipine. The concentration-response relation was analyzed
      using logistic regression, and pharmacokinetic models were applied to the data
      using population analysis. RESULTS: There were significant decreases in mean
      arterial blood pressure and systemic vascular resistance at doses greater than or
      equal to 1.37 microg. kg-1. min-1. There were no changes in heart rate, central
      venous pressure, pulmonary artery occlusion pressure, or cardiac index with
      increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater
      decrease in mean arterial pressure was 9.7 microg/l and for a 20% or greater
      decrease in mean arterial pressure was 26.3 microg/l. The pharmacokinetics of
      clevidipine were best described with a three-compartment model with a volume of
      distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug
      disposition had a half-life of 0.6 min. The context-sensitive half-time is less
      than 2 min for up to 12 h of administration. CONCLUSION: Clevidipine is a calcium
      channel antagonist with a very short duration of action that effectively
      decreases systemic vascular resistance and mean arterial pressure without
      changing heart rate, cardiac index, or cardiac filling pressures.

PMID- 11981148
TI  - Recombinant human transgenic antithrombin in cardiac surgery: a dose-finding
      study.
AB  - BACKGROUND: Acquired antithrombin III (AT) deficiency may render heparin less
      effective during cardiac surgery and cardiopulmonary bypass (CPB). The authors
      examined the pharmacodynamics and optimal dose of recombinant human AT (rh-AT)
      needed to maintain normal AT activity during CPB, optimize the anticoagulant
      response to heparin, and attenuate excessive activation of the hemostatic system
      in patients undergoing coronary artery bypass grafting. METHODS: Thirty-six
      patients scheduled to undergo elective primary coronary artery bypass grafting
      and who had received heparin for 12 h or more before surgery were enrolled in the
      study. Ten cohorts of three patients each received rh-AT in doses of 10, 25, 50,
      75, 100, 125, 175, or 200 U/kg, a cohort of six patients received 150 U/kg of rh
      AT, and a control group of six patients received placebo. RESULTS: Antithrombin
      III activity exceeded 600 U/dl before CPB at the highest dose (200 U/kg). Doses
      of 75 U/kg rh-AT normalized AT activity to 100 U/dl during CPB. Activated
      clotting times during CPB were significantly (P < 0.0001) greater in patients who
      received rh-AT (844 +/- 191 s) compared with placebo patients (531 +/- 180 s).
      Significant (P = 0.001) inverse relations were observed between rh-AT dose and
      both fibrin monomer (r = -0.51) and D-dimer (r = -0.51) concentrations. No
      appreciable adverse events were observed with any rh-AT doses used in the study.
      CONCLUSIONS: Supplementation of native AT with transgenically produced protein
      (rh-AT) in cardiac surgical patients was well tolerated and resulted in higher
      activated clotting times during CPB and decreased levels of fibrin monomer and D
      dimer.

PMID- 11981149
TI  - The influence of hyperoxic ventilation during sodium nitroprusside-induced
      hypotension on skeletal muscle tissue oxygen tension.
AB  - BACKGROUND: Increasing inspired oxygen concentrations might provide a simple and
      effective intervention to increase oxygen tension in tissues during controlled
      hypotension. To test this hypothesis, the influence of hyperoxic ventilation
      (100% O2) on skeletal muscle oxygen partial pressure (Ptio2) in patients
      receiving sodium nitroprusside-induced controlled hypotension was studied.
      METHODS: Forty-two patients undergoing radical prostatectomy were prospectively
      studied and randomly divided into three groups as follows: (1) Controlled
      hypotension induced by sodium nitroprusside (mean arterial blood pressure, 50
      mmHg) and hyperoxic ventilation (CH-100%; n = 14); (2) controlled hypotension and
      ventilation with 50% O2 in nitrous oxide (CH-50%; n = 14); and (3) standard
      normotensive anesthesia with 50% O2 in nitrous oxide (control; n = 14). Ptio2
      values were measured continuously in all patients using implantable polarographic
      microprobes. Arterial blood gases and lactate concentrations were analyzed in 30
      min intervals. RESULTS: Surgical blood loss and transfusion requirements were
      significantly reduced in both groups receiving hypotensive anesthesia. During
      surgery, arterial partial pressure of oxy-gen and arterial oxygen content were
      significantly higher in patients of the CH-100% group. Baseline values of Ptio2
      were comparable between the groups (CH-50%: 25.0 +/- 0.7 mmHg; CH-100%: 25.2 +/-
      0.2 mmHg; control: 24.5 +/- 0.2 mmHg). After a transient increase in Ptio2 in the
      CH-100% group during normotension, Ptio2 values returned to baseline and remained
      unchanged in the control group. Ptio2 decreased significantly during the
      hypotensive period in the CH-50% group. The lowest mean Ptio2 values were 15.0 +/
      4.1 mmHg in the CH-50% group, 24.2 +/- 4.9 mmHg in the CH-100% group, and 23.5
      +/- 3.8 mmHg in the control group. There were no significant changes in lactate
      plasma concentrations in any group throughout the study period. CONCLUSIONS:
      Hyperoxic ventilation improved skeletal muscle tissue oxygenation during sodium
      nitroprusside-induced hypotension. This improved local tissue oxygenation seems
      to be most likely due to an increase in convective oxygen transport and the
      attenuation of hyperoxemia-induced arteriolar vasoconstriction by sodium
      nitroprusside.

PMID- 11981150
TI  - Effects of clonidine on postoperative nausea and vomiting in breast cancer
      surgery.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is still common, especially
      among female patients. Our hypothesis is that coinduction with clonidine reduces
      the incidence of PONV in adult patients undergoing breast cancer surgery.
      METHODS: Sixty-eight women premedicated with midazolam were randomly allocated to
      coinduction with intravenous clonidine (group C) or placebo (group P) in this
      prospective, double-blind study. Anesthesia was standardized (laryngeal mask
      airway, fentanyl, propofol, sevoflurane, nitrous oxide, and oxygen). Hemodynamic
      parameters and the requirements for propofol, sevoflurane, and the postoperative
      need for ketobemidone were noted. The primary endpoints studied were the number
      of PONV-free patients and patient satisfaction with respect to PONV. RESULTS:
      Patients in group C had a significantly reduced need for propofol (P < 0.04) and
      sevoflurane (P < 0.01) and a reduced early need for ketobemidone (P < 0.04).
      There were significantly more PONV-free patients in group C compared with group P
      (20 and 11 of 30, respectively; P < 0.04). The number needed to treat was 3.3
      (95% confidence interval, 1.8, 16.9). Intraoperative blood pressure,
      postoperative heart rate, and postoperative blood pressure were all significantly
      lower in group C compared with group P, but were not considered to be of clinical
      importance. No negative side effects were recorded. CONCLUSION: Coinduction with
      clonidine significantly increased the number of PONV-free patients after breast
      cancer surgery with general anesthesia.

PMID- 11981151
TI  - Utility of whole blood hemostatometry using the clot signature analyzer for
      assessment of hemostasis in cardiac surgery.
AB  - BACKGROUND: A hemostatic monitor capable of rapid, accurate detection of clinical
      coagulopathy within the operating room could improve management of bleeding after
      cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer
      that measures global hemostasis in whole blood. The authors hypothesized that
      point-of-care hemostatometry could detect a clinical coagulopathic state in
      cardiac surgical patients. METHODS: Fifty-seven adult patients scheduled for a
      variety of elective cardiac surgical procedures were studied. Anesthesia, CPB,
      heparin anticoagulation, protamine reversal, and transfusion for post-CPB
      bleeding were all managed by standardized protocol. Clinical coagulopathy was
      defined by the need for platelet or fresh frozen plasma transfusion. The Clot
      Signature Analyzer collagen-induced thrombus formation (CITF) assay measured
      platelet-mediated hemostasis in vitro. The activated clotting time, platelet
      count, prothrombin time, activated partial thromboplastin time, and fibrinogen
      concentration were also measured. RESULTS: The postprotamine CITF was greater in
      patients who required hemostatic transfusion than in those who did not (17.6 +/-
      8.0 min vs. 10.5 +/- 5.7 min, respectively; P < 0.01). Postprotamine CITF values
      were highly correlated with platelet and fresh frozen plasma transfusion
      (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver
      operator characteristic curves showed a highly significant relation between the
      postprotamine CITF and intraoperative platelet and fresh frozen plasma
      transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity,
      specificity, positive and negative predictive values at cutoffs of 12-14 min.
      Logistic regression demonstrated that the CITF was independently predictive of
      post-CPB hemostatic transfusion, but standard hemostatic assays were not.
      CONCLUSIONS: The Clot Signature Analyzer CITF detects a clinical coagulopathic
      state after CPB and is independently predictive of the need for hemostatic
      transfusion. Hemostatometry has potential utility for monitoring hemostasis in
      cardiac surgery.

PMID- 11981152
TI  - Effect of epidural epinephrine on the minimum local analgesic concentration of
      epidural bupivacaine in labor.
AB  - BACKGROUND: The minimum local analgesic concentration (MLAC) has been defined as
      the median effective local analgesic concentration in a 20-ml volume for epidural
      analgesia in the first stage of labor. The aim of this study was to determine the
      local anesthetic-sparing efficacy of epidural epinephrine by its effect on the
      MLAC of bupivacaine. METHODS: In this double-blind, randomized, prospective
      study, 70 parturients who were at 7 cm or less cervical dilation and who
      requested epidural analgesia were allocated to one of two groups. After lumbar
      epidural catheter placement, 20 ml bupivacaine (n = 35) or bupivacaine with
      epinephrine 1:300,000 (n = 35) was administered. The concentration of bupivacaine
      was determined by the response of the previous patient in that group to a higher
      or lower concentration using up-down sequential allocation. Analgesic efficacy
      was assessed using 100-mm visual analog pain scores, with 10 mm or less within 30
      min defined as effective. RESULTS: The MLAC of bupivacaine alone was 0.091%
      wt/vol (95% confidence interval, 0.081-0.102). The addition of epinephrine
      1:300,000 (66.7 microg) resulted in a significant reduction (P < 0.01) in the
      MLAC of bupivacaine to 0.065% wt/vol (95% confidence interval, 0.047-0.083). The
      lowest maternal blood pressure was significantly lower in the bupivacaine
      epinephrine group (P = 0.03). There were statistically significant reductions in
      fetal heart rate (P = 0.011) in the bupivacaine-epinephrine group that were not
      clinically significant. CONCLUSIONS: The addition of epidural epinephrine
      1:300,000 (66 microg) resulted in a significant 29% reduction in the MLAC of
      bupivacaine. Coincident reductions in fetal heart rate and maternal blood
      pressure were also observed that were not clinically significant.

PMID- 11981153
TI  - Assessment of the intrarater and interrater reliability of an established
      clinical task analysis methodology.
AB  - BACKGROUND: Task analysis may be useful for assessing how anesthesiologists alter
      their behavior in response to different clinical situations. In this study, the
      authors examined the intraobserver and interobserver reliability of an
      established task analysis methodology. METHODS: During 20 routine anesthetic
      procedures, a trained observer sat in the operating room and categorized in real
      time the anesthetist's activities into 38 task categories. Two weeks later, the
      same observer performed task analysis from videotapes obtained intraoperatively.
      A different observer performed task analysis from the videotapes on two separate
      occasions. Data were analyzed for percent of time spent on each task category,
      average task duration, and number of task occurrences. Rater reliability and
      agreement were assessed using intraclass correlation coefficients. RESULTS:
      Intrarater reliability was generally good for categorization of percent time on
      task and task occurrence (mean intraclass correlation coefficients of 0.84-0.97).
      There was a comparably high concordance between real-time and video analyses.
      Interrater reliability was generally good for percent time and task occurrence
      measurements. However, the interrater reliability of the task duration metric was
      unsatisfactory, primarily because of the technique used to capture multitasking.
      CONCLUSIONS: A task analysis technique used in anesthesia research for several
      decades showed good intrarater reliability. Off-line analysis of videotapes is a
      viable alternative to real-time data collection. Acceptable interrater
      reliability requires the use of strict task definitions, sophisticated software,
      and rigorous observer training. New techniques must be developed to more
      accurately capture multitasking. Substantial effort is required to conduct task
      analyses that will have sufficient reliability for purposes of research or
      clinical evaluation.

PMID- 11981154
TI  - Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis,
      and death following primary hip or knee arthroplasty.
AB  - BACKGROUND: There is limited information about the frequency of perioperative
      complications after elective primary orthopedic total hip and knee arthroplasty
      in contemporary practice. The purpose of this study was to determine the
      frequency of clinically relevant myocardial infarction, pulmonary embolism, deep
      venous thrombosis, and death within 30 days after elective primary hip or knee
      arthroplasty treated according to contemporary perioperative management. METHODS:
      The authors examined the medical records of consecutive patients undergoing hip
      or knee arthroplasty at their institution in a 10-yr period. Prospectively
      collected databases were used to identify patients with the diagnosis of
      myocardial infarction, pulmonary embolism, deep venous thrombosis, or death using
      strict validation criteria and diagnostic-certainty categories. RESULTS: A total
      of 10,244 patients underwent primary total hip or knee arthroplasty in the period
      of study. Of these, 224 patients had one or more adverse events (overall event
      rate: 2.2%; myocardial infarction: 0.4%; pulmonary embolism: 0.7%; deep venous
      thrombosis: 1.5%; death: 0.5%). Most adverse events (myocardial infarction,
      pulmonary embolism, and death) increased in frequency with older age,
      particularly for patients aged 70 yr or older. Myocardial infarction occurred
      more frequently in male patients. There were no differences in the overall event
      frequency between types of procedure. However, pulmonary embolism was highest in
      patients undergoing bilateral knee operations. CONCLUSIONS: The overall frequency
      of serious complications within 30 days after primary total hip or knee
      arthroplasty with contemporary practice was 2.2%. Accurate knowledge of the
      perioperative risks associated with widely performed elective operations can be
      used to implement management strategies that may further improve patient outcomes
      and decrease cost.

PMID- 11981155
TI  - Ketamine suppresses platelet aggregation possibly by suppressed inositol
      triphosphate formation and subsequent suppression of cytosolic calcium increase.
AB  - BACKGROUND: Ketamine has been shown to suppress platelet aggregation, but its
      mechanisms of action have not been defined. The purpose of the current study is
      to clarify the effects of ketamine on human platelet aggregation and to elucidate
      the underlying mechanisms of its action. METHODS: Platelet aggregation was
      measured using an eight-channel aggregometer, and cytosolic free calcium
      concentration was measured in Fura-2/AM-loaded platelets using a fluorometer.
      Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially
      available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding
      affinity and expression, Scatchard analysis was performed using [3H]S145, a
      specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed.
      The membrane-bound guanosine 5'-triphosphatase activity was determined using
      [gamma-32P]guanosine triphosphate by liquid scintillation analyzer. RESULTS:
      Ketamine (500 microm) suppressed aggregation induced by adenosine diphosphate
      (0.5 microm), epinephrine (1 microm), (+)-9,11-epithia-11,12-methano-TXA2 (STA2)
      (0.5 microm), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/-
      16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 microm-1 mm)
      also suppressed thrombin- and STA2-induced cytosolic free calcium concentration
      increase dose dependently. Although ketamine (2 mm) had no effect on TXA2
      receptor expression and its binding affinity, it (1 mm) suppressed intracellular
      peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39
      +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and
      it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02
      units/ml) and STA2 (0.5 microm) to 50.3 +/- 3.2 and 67.5 +/- 5.5% versus zero
      control, respectively. CONCLUSION: Ketamine inhibits human platelet aggregation
      possibly by suppressed IP3 formation and subsequent suppression of cytosolic free
      calcium concentration. The site of action of ketamine is neither TXA2 nor
      thrombin binding sites but possibly receptor-coupled mechanisms, including G
      protein.

PMID- 11981156
TI  - Role of the rostral medial medulla in the development of primary and secondary
      hyperalgesia after incision in the rat.
AB  - BACKGROUND: Descending influences from the rostral medial medulla (RMM)
      contribute to secondary hyperalgesia in persistent inflammatory, neuropathic, and
      visceral pain models. The current study examined if descending inhibition or
      facilitation from the RMM modulates primary and secondary hyperalgesia after
      incision in the rat hind limb. METHODS: Bilateral RMM lesions were produced using
      the soma-selective neurotoxin ibotenic acid, and the effect of RMM lesion was
      examined on primary and secondary hyperalgesia 5 days after a plantar or
      gastrocnemius incision, respectively. RESULTS: Plantar incision reduced
      withdrawal thresholds to von Frey filaments applied adjacent to the incision
      (primary punctate hyperalgesia). The withdrawal thresholds were the same in RMM
      lesioned and sham-operated rats. The response frequency to a blunt mechanical
      stimulus after plantar incision was increased (primary nonpunctate hyperalgesia)
      in both groups. Nonpunctate hyperalgesia was greater in lesioned rats on
      postoperative day 2 only; all other measures were not different. Primary heat
      hyperalgesia after plantar incision was not modulated by RMM lesion. Secondary
      punctate hyperalgesia after gastrocnemius incision was not affected by RMM
      lesion. Gastrocnemius incision did not produce secondary nonpunctate or heat
      hyperalgesia in either RMM lesion or sham rats. CONCLUSION: Primary and secondary
      hyperalgesia after an incision were not modulated by descending influence from
      the RMM. The lack of contribution of descending facilitatory influences from the
      RMM to secondary hyperalgesia after gastrocnemius incision supports the notion
      that incision-induced pain involves dissimilar mechanisms compared with
      inflammatory and neuropathic pain.

PMID- 11981157
TI  - Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic
      pain.
AB  - BACKGROUND: This study tests the hypothesis that loss of spinal activity of gamma
      aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed
      after peripheral nerve injury. METHODS: Intrathecal catheters were implanted in
      male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal
      latency to immersion of the tail in a 52 degrees C water bath. Nerve injury was
      produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14
      days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia
      were established. Tactile allodynia was quantitated using the threshold to
      withdrawal of the hind paw on probing with von Frey filaments. Thermal
      hyperalgesia was quantitated using the latency to withdrawal of the hind paw from
      radiant heat. Motor function was tested using a rotarod apparatus. RESULTS:
      Spinal administration of the GABAA receptor antagonist bicuculline or the GABAB
      receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia
      in normal rats. The GABAB receptor agonist baclofen, administered spinally,
      produced antinociception in the tail-flick test, whereas the GABAA receptor
      agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile
      allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen
      but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats
      beyond preoperative values. Baclofen but not isoguvacine impaired motor function.
      CONCLUSIONS: Pharmacologic inhibition of intrinsic GABA tone in normal rats
      resulted in tactile allodynia and thermal hyperalgesia, consistent with the
      hypothesis being tested. Exogenous administration of GABA agonists reversed
      spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with
      this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic
      effects, whereas assessment of the effects of baclofen was complicated by motor
      dysfunction. Spinal GABAA agonists may provide a specific therapy for neuropathic
      pain.

PMID- 11981158
TI  - Effects of analgesics on delayed postherpetic pain in mice.
AB  - BACKGROUND: Postherpetic neuralgia is pain that persists long after the
      disappearance of the cutaneous lesions of herpes zoster. However, the mechanisms
      of this delayed pain are unclear. Herpes simplex virus infection induces
      cutaneous lesions and pain-related responses in mice. The authors examined
      whether such responses would persist after the disappearance of the cutaneous
      lesions and whether some analgesics would be effective against them. METHODS:
      Female BALB/c mice were inoculated with herpes simplex virus type 1 on the
      unilateral hind paw. Pain-related responses of hind paw were determined using von
      Frey filaments. Beginning 5 days after inoculation, mice were given perorally the
      antiherpes agent acyclovir five times a day for 7 days. Effects of morphine (3-5
      mg/kg subcutaneously), gabapentin (30-100 mg/kg perorally), mexiletine (10-30
      mg/kg intraperitoneally), and diclofenac (30 mg/kg intraperitoneally) on pain
      related responses were examined on days 25-35 after inoculation. RESULTS: Viral
      inoculation induced cutaneous lesions and pain-related responses beginning on day
      5 after inoculation. Acyclovir treatment healed all skin lesions by day 15 after
      inoculation. Approximately half of the mice given acyclovir showed pain-related
      responses at least until day 40 after inoculation. Morphine, gabapentin, and
      mexiletine dose-dependently inhibited pain-related responses, but diclofenac had
      no effects. CONCLUSIONS: The authors show a mouse model of delayed postherpetic
      pain. This may be useful for manifesting the mechanisms of postherpetic neuralgia
      and the factors contributing to the transition from acute herpetic pain to
      delayed postherpetic pain. This may also be useful for the development of new
      analgesics against postherpetic neuralgia.

PMID- 11981159
TI  - Intracerebroventricular morphine produces antinociception by evoking gamma
      aminobutyric acid release through activation of 5-hydroxytryptamine 3 receptors
      in the spinal cord.
AB  - BACKGROUND: It has been generally considered that supraspinal morphine activates
      the serotonergic descending inhibitory system and releases serotonin (5
      hydroxytryptamine [5-HT]) in the spinal cord, producing antinociception through
      activation of 5-HT receptors. The involvement of a spinal gamma-aminobutyric acid
      mediated (GABAergic) system is also suggested in supraspinal morphine
      antinociception. It has been reported that spinal GABAergic system contributes to
      5-HT3 receptor-mediated antinociception. In this study, the authors investigated
      the contribution of spinal 5-HT3 receptor and the GABAergic system in the
      intracerebroventricular morphine-induced antinociception. METHODS: Male Sprague
      Dawley rats were used. Using the spinal microdialysis method, concentrations of 5
      HT and GABA were measured after intracerebroventricular morphine administration.
      The effect of intracerebroventricular naloxone or spinal perfusion of a selective
      5-HT3 receptor antagonist 3-tropanyl-indole-3-carboxylate methiodide on the
      spinal release of GABA after intracerebroventricular morphine administration was
      also examined. In the behavioral study, involvement of 5-HT3 receptors or GABAA
      receptors in the intracerebroventricular morphine-induced antinociceptive effect
      was investigated using the tail-flick test. RESULTS: Intracerebroventricular
      morphine (40 nmol) significantly increased spinal GABA and 5-HT release. Evoked
      spinal GABA release was reversed by intracerebroventricular naloxone (40 nmol) or
      spinal perfusion of 3-tropanyl-indole-3-carboxylate methiodide (1 mm). In the
      behavioral study, intracerebroventricular morphine produced significant
      antinociception. Intrathecal administration of either GABAA receptor antagonist
      bicuculine or 3-tropanyl-indole-3-carboxylate methiodide but not vehicle reversed
      the morphine-induced antinociceptive effect. CONCLUSION: Intracerebroventricular
      morphine evokes spinal GABA release via the activation of 5-HT3 receptors in the
      spinal cord, resulting in antinociceptive effect.

PMID- 11981160
TI  - Propofol anesthesia compared to awake reduces infarct size in rats.
AB  - BACKGROUND: Propofol has not been studied directly in animals subject to cerebral
      ischemia in the conscious state. Strokes are usually induced in animals while
      they are anesthetized, making it difficult to eliminate anesthetic interactions
      as a complicating factor. Therefore, to compare the neuroprotective effects of
      propofol to the unanesthetized state, experiments were performed using a model
      that induces a stroke in the conscious rat. METHODS: Cerebral ischemia was
      induced in awake Wistar rats by a local intracerebral injection of the potent
      vasoconstrictor endothelin. Four days before the strokes were induced, a guide
      cannula was implanted for the injection of endothelin. On the day of the
      experiment, endothelin (6.0 pmol in 3 microl) was injected into the striatum.
      Propofol (25 or 15 mg. kg-1. h-1) or intralipid (vehicle) were infused for 4 h
      starting immediately after the endothelin injection. In another series, the
      propofol infusion was begun 1 h after the endothelin injection and continued for
      4 h. Three days later, the animals were killed, and the brains were sectioned and
      stained. RESULTS: The propofol group (25 mg. kg-1. h-1) had a significantly
      reduced infarct size (0.7 +/- 0.21 mm3, first 4 h; 0.27 +/- 0.07 mm3, started 1 h
      after initiation of infarct) compared with the intralipid controls (3.40 +/- 0.53
      mm3). To exclude a direct interaction between propofol and endothelin, in
      thiobutabarbital anesthetized rats, endothelin-induced cerebral vasoconstriction
      was examined using videomicroscopy, with or without propofol. Propofol had no
      effect on the magnitude or time course of the endothelin-induced
      vasoconstriction. CONCLUSIONS: The results show that concurrent or delayed
      administration of propofol is neuroprotective.

PMID- 11981161
TI  - Involvement of the mitogen-activated protein kinase family in tetracaine-induced
      PC12 cell death.
AB  - BACKGROUND: To explore whether cytotoxicity of local anesthetics is related to
      apoptosis, the authors examined how local anesthetics affect mitogen-activated
      protein kinase (MAPK) family members, extracellular signal-regulated kinases
      (ERKs), c-Jun N-terminal kinases (JNKs)-stress-activated protein kinases, and p38
      kinase, which are known to play important roles in apoptosis. METHODS: Cell death
      was evaluated using PC12 cells. Morphologic changes of cells, cellular membrane,
      and nuclei were observed. DNA fragmentation was electrophoretically assayed.
      Western blot analysis was performed to analyze phosphorylation of the MAPK
      family, cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase.
      Intracellular Ca2+ concentration was measured using a calcium indicator dye.
      RESULTS: Tetracaine-induced cell death was shown in a time- and concentration
      dependent manner and characterized by nuclear condensation or fragmentation,
      membrane blebbing, and internucleosomal DNA fragmentation. Caspase-3 activation
      and phosphorylation of ERK, JNK, and p38 occurred in the cell death. PD98059, an
      inhibitor of ERK, enhanced tetracaine-induced cell death and JNK phosphorylation,
      whereas ERK phosphorylation was inhibited. Curcumin, an inhibitor of JNK pathway,
      attenuated the cell death. Increase of intracellular Ca2+ concentration was
      detected. In addition to the increase of ERK phosphorylation and the decrease of
      JNK phosphorylation, two Ca2+ chelators protected cells from death. Neither cell
      death nor phosphorylation of the MAPK family was caused by tetrodotoxin.
      Nifedipine did not affect tetracaine-induced apoptosis. CONCLUSIONS: Tetracaine
      induces apoptosis of PC12 cells via the MAPK family. ERK activation protects
      cells from death, but JNK plays the opposite role. Toxic Ca2+ influx caused by
      tetracaine seems to be responsible for the cell death, but blocking of Na+
      channels or L-type Ca2+ channels is unlikely involved in the tetracaine's action
      for apoptosis.

PMID- 11981162
TI  - Thiopental inhibits the activation of nuclear factor kappaB.
AB  - BACKGROUND: Thiopental is frequently used for the treatment of intracranial
      hypertension after severe head injury. Its long-term administration increases the
      incidence of nosocomial infections, which contributes to the high mortality rate
      of these patients. However, the mechanism of its immunosuppressing effect remains
      unknown. METHODS: The effect of thiopental (200-1000 microg/ml) on the activation
      of the nuclear transcription factor kappaB (NF-kappaB; electrophoretic mobility
      shift assays), on NF-kappaB-driven reporter gene activity (transient transfection
      assays), on the expression of NF-kappaB target genes (enzyme-linked
      immunoassays), on T-cell activation (flow cytometric analyses of CD69
      expression), and on the content of the NF-kappaB inhibitor IkappaB-alpha (Western
      blotting) was studied in human T lymphocytes in vitro. RESULTS: Thiopental
      inhibited the activation of the transcription factor NF-kappaB but did not alter
      the activity of the cyclic adenosine monophosphate response element binding
      protein. Other barbiturates (methohexital), anesthetics (etomidate, propofol,
      ketamine), or opioids (fentanyl, morphine) did not affect NF-kappaB activation.
      Thiopental-mediated suppression of NF-kappaB could be observed in Jurkat cells
      and in primary CD3+ lymphocytes from healthy volunteers, was time- and
      concentration-dependent, occurred at concentrations that are clinically achieved,
      and persisted for hours after the incubation. It was associated with an
      inhibition of NF-kappaB-driven reporter gene activity, of the expression of
      interleukin-2, -6, and -8, and interferon gamma, and of the activation of CD3+
      lymphocytes. Suppression of NF-kappaB appeared to involve reduced degradation of
      IkappaB-alpha. CONCLUSION: The results demonstrate that thiopental inhibits the
      activation of NF-kappaB and may thus provide a molecular mechanism for some of
      the immunosuppressing effects associated with thiopental therapy.

PMID- 11981163
TI  - Isoflurane depresses baroreflex control of heart rate in decerebrate rats.
AB  - BACKGROUND: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly
      understood mechanisms. The authors examined whether suprapontine central nervous
      system cardiovascular regulatory sites are required for anesthetic depression.
      METHODS: The effects of isoflurane (1 and 2 rat minimum alveolar concentration
      [MAC]) on the baroreflex control of HR were determined in sham intact and
      midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12
      microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses
      to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to
      HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper
      HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact
      and two decerebrate) were studied before, during, and after isoflurane. To assess
      sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg
      atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered
      systemically. RESULTS: Decerebration did not alter resting MAP and HR or
      baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in
      brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by
      depressing peak reflex tachycardia. Maximal reflex bradycardia during increases
      in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter
      maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked
      reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic
      components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and
      decreased BP50 in both groups. CONCLUSIONS: Isoflurane depresses HR baroreflex
      control by actions that do not require suprapontine central nervous system sites.
      Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic
      nervous system.

PMID- 11981164
TI  - Isoflurane causes anterograde but not retrograde amnesia for pavlovian fear
      conditioning.
AB  - BACKGROUND: Production of retrograde amnesia by anesthetics would indicate that
      these drugs can disrupt mechanisms that stabilize memory. Such disruption would
      allow suppression of memory of previous untoward events. The authors examined
      whether isoflurane provides retrograde amnesia for classic (Pavlovian) fear
      conditioning. METHODS: Rats were trained to fear tone by applying three (three
      trial) or one (one-trial) tone-shock pairs while breathing various constant
      concentrations of isoflurane. Immediately after training, isoflurane
      administration was either discontinued, maintained unchanged, or rapidly
      increased to 1.0 minimum alveolar concentration for 1 h longer. Groups of rats
      were similarly trained to fear context while breathing isoflurane by applying
      shocks (without tones) in a distinctive environment. The next day, memory for the
      conditioned stimuli was determined by presenting the tone or context (without
      shock) and measuring the proportion of time each rat froze (appeared immobile).
      For each conditioning procedure, the effects of the three posttraining isoflurane
      treatments were compared. RESULTS: Rapid increases in posttraining isoflurane
      administration did not suppress conditioned fear for any of the training
      procedures. In contrast, isoflurane administration during conditioning dose
      dependently suppressed conditioning (P < 0.05). Training to tone was more
      resistant to the effects of isoflurane than training to context (P < 0.05), and
      the three-trial learning procedure was more was more resistant than the one-trial
      procedure (P < 0.05). CONCLUSIONS: Isoflurane provided intense dose-dependent
      anterograde but not retrograde amnesia for classic fear conditioning. Isoflurane
      appears to disrupt memory processes that occur at or within a few minutes of the
      conditioning procedure.

PMID- 11981165
TI  - What sample sizes are required for pooling surgical case durations among
      facilities to decrease the incidence of procedures with little historical data?
AB  - BACKGROUND: Better predictions of each case's duration would reduce operating
      room labor costs and patient waiting times. A barrier to using historical case
      duration data to predict the duration of future cases is the absence for some
      cases of previous data for the same scheduled procedure from the same facility.
      The authors examined sample size requirements for pooling case duration data from
      several facilities to create a 90% chance of having case duration data for almost
      all procedures. METHODS: Four academic medical centers provided data, totaling
      200,401 cases classified by the scheduled Current Procedural Terminology codes.
      RESULTS: The 12% of cases in which procedures occurred once or twice accounted
      for 79% of procedures or combinations of procedures. When a procedure was being
      performed for the first time at a facility, that same procedure had been
      performed previously at least once at one or more of the other three facilities
      only 13-25% of the time. More than 1 million cases would be needed to have a 90%
      chance of having at least 3 cases for each procedure observed in the original
      200,401 cases. However, with N = 200,401 cases in our initial data set, we
      observed less than one third of the estimated total number of possible
      procedures. CONCLUSIONS: The lack of historical case duration data for scheduled
      procedures is an important cause of inaccuracy in predicting case durations.
      However, millions of cases probably would be required to provide historical case
      duration data for almost all procedures.

PMID- 11981166
TI  - Platelet glycoprotein IIb/IIIa antagonists: pharmacology and clinical
      developments.

PMID- 11981167
TI  - An unexplained death: Hannah Greener and chloroform.

PMID- 11981168
TI  - Complex regional pain syndrome I (reflex sympathetic dystrophy).

PMID- 11981169
TI  - Recurrent pulmonary embolism during liver transplantation: possible role of
      hepatitis B immune globulin as a causative agent.

PMID- 11981170
TI  - Unilateral cerebral oxygen desaturation during emergent repair of a DeBakey type
      1 aortic dissection: potential aversion of a major catastrophe.

PMID- 11981171
TI  - Ketamine combined with morphine for the management of pain in an opioid addict.

PMID- 11981172
TI  - Potential disaster in airway management: a misguided airway exchange catheter via
      a hole bitten into a univent endotracheal tube.

PMID- 11981173
TI  - Mitochondrial defects and anesthetic sensitivity.

PMID- 11981174
TI  - Febrile reaction to subarachnoid baclofen administration.

PMID- 11981175
TI  - Volatile agents depress contractility in children.

PMID- 11981176
TI  - Do sevoflurane and desflurane differ in upper airway reactivity?

PMID- 11981177
TI  - Does nitrous oxide really induce c-Fos expression related to its analgesic
      effect?

PMID- 11981178
TI  - Obtaining informed consent.

PMID- 11981179
TI  - Successful resuscitation after maternal cardiac arrest by immediate cesarean
      section in the labor room.

PMID- 11981180
TI  - Another reason to choose the left molar approach of laryngoscopy: to spare the
      incisor teeth.

PMID- 11981182
TI  - John Bostwick, Pickerell Award, 2001.

PMID- 11981183
TI  - Importance of the periareolar approach in the augmentation of the ptotic breast.
AB  - This is a retrospective review of 66 patients with grade II breast ptosis who
      underwent augmentation mammaplasty from January 1996 to January 2001. Of these 66
      patients, 17 were augmented using a periareolar approach, and 49 were augmented
      using an inframammary approach. All patients had textured saline implants, and 64
      of 66 patients had the implants placed in a submuscular position. Mean
      photographic follow-up was 4.8 months (range, 6 weeks-1 year). When compared with
      an inframammary approach in the presence of grade II ptosis, a periareolar
      approach results in improved fill of the lower pole of the breast, improved
      centralization of the nipple on the breast mound, and lessening or elimination of
      undesirable upper pole fullness.

PMID- 11981184
TI  - Evaluation and treatment of velopharyngeal insufficiency: the University of
      Florida experience.
AB  - This retrospective study spans the years 1988 to 2000 and looks specifically at
      the treatment procedures and outcomes for the correction of velopharyngeal
      insufficiency (VPI). Ninety-eight patients underwent preoperative assessment by
      speech pathologists that included perceptual speech evaluation, videofluoroscopy,
      and, for some, nasendoscopy. Based on this evaluation protocol, a specific
      surgical procedure was chosen to serve the patients' needs. The four procedures
      of choice were the palatal pushback with a pharyngeal flap lining, sphincter
      pharyngoplasty, a superiorly based obturating pharyngeal flap, and Furlow
      palatoplasty. The criteria for selecting these procedures are reviewed. The
      results revealed VPI resolution and the establishment of normal nonnasal speech
      in more than 95% of the 75 patients for whom outcomes were determined. This study
      reiterates the importance of thorough preoperative evaluation and the
      individualization of the secondary corrective procedure.

PMID- 11981185
TI  - Posttraumatic craniofacial reconstruction using combined resorbable and
      nonresorbable fixation systems.
AB  - The facial skeleton consists of high-stress-bearing buttresses and low-stress
      bearing curved surfaces. The buttresses are like trusses made of beams, struts,
      and columns. They resist tensile, compressive, and shear loading. The thin,
      curved, planar surfaces provide for the support and partitioning of the soft
      tissue. The trusses are strong and one-dimensional whereas the planes are weak
      and two-dimensional. Ideally, strong one-dimensional fixation systems should be
      used for the former; weaker, two-dimensional systems should be used for the
      latter. The authors report their clinical experience of using such combined
      approaches to the treatment of facial fractures using rigid, titanium mini-plates
      and screws for the buttresses and polymeric resorbable meshes for the curved
      planes. For an 11-month period (August 2000 to June 2001), nine patients (7 males
      and 2 females) with a mean age of 33.7 years were treated in this fashion. The
      resorbable meshes were deployed for the reconstitution of the orbital walls and
      the anterior wall of the maxillary sinus. No enophthalmos, globe dystopia, or
      diplopia occurred during the short mean follow-up of 10 months (4-17 months).
      There were no infections or sterile abscess formations. This type of combined use
      of fixation systems appears to be safe and effective. More patients and more
      extensive follow-ups are obviously needed.

PMID- 11981186
TI  - Perforator-based forearm and hand adipofascial flaps for the coverage of
      difficult dorsal hand wounds.
AB  - The author presents several case studies of alternative therapy for large and
      small dorsal hand and finger defects. These alternatives avoid the need for a
      lengthy free flap procedure, avoid the meticulous dissection required by the
      posterior interosseous flap, and avoid the loss of radial artery required by the
      reverse radial forearm flap. Distally based hand and forearm adipofascial flaps
      consist of the subcutaneous fat and fascia of the hand and/or forearm. They are
      easy to elevate, with operative times typically less than 2 hours, and can cover
      surfaces ranging from an individual finger to the entire dorsum of the hand. The
      blood supply is based on the rich profusion of perforators that exist in the hand
      and wrist. If desired, a skin paddle can be included with these flaps. These
      techniques are an important addition to the plastic and hand surgeon's
      armamentarium.

PMID- 11981187
TI  - Innovative techniques in bony reconstruction to facilitate hand salvage.
AB  - Mutilating injuries of the hand and congenital hand anomalies can present
      challenging reconstructive scenarios for salvage and restoration of function.
      During a 5-year period from 1993 to 1997, the plastic and reconstructive surgical
      unit of East Carolina University Medical Center was presented with a series of
      unique reconstructive challenges as a result of complex hand injuries that
      resulted in unexpected opportunities for the salvage of distal components. These
      traumatic injuries were unique in that, although devastating to the hand, they
      left the opportunity for salvage of distal vascularized and sensate components of
      the hand. Other unique challenges arose as a result of patients who did not want
      to pursue alternative reconstructive options such as toe-to-hand transfers or
      pollicization. These cases are presented to emphasize alternative algorithms to
      standard hand reconstruction in complex scenarios. Three patients presented with
      distal viable (vascularized and sensate) phalangeal components with proximal
      complex bony defects, 1 patient presented with a complex thumb defect and
      declined standard therapy, and 1 patient presented with a congenital thumb
      anomaly and declined standard therapy. All flaps survived and all hands were
      saved. These patients illustrate the clinical feasibility of osteocutaneous and
      free osseous grafting to provide strut stabilization in metacarpal defects and to
      preserve an opposable post after thumb amputation or thumb anomaly.

PMID- 11981188
TI  - Surgical treatment of nasal hemangiomas.
AB  - The treatment of nasal hemangiomas continues to be controversial. The authors'
      experience with early surgical treatment of nasal hemangiomas is presented. This
      retrospective study includes 11 patients. Surgical intervention consisted of
      excision of the nasal hemangioma and reconstruction by local tissue transfer or
      rearrangement. Age at surgery ranged from 10 months to 6.5 years (mean age, 2.2
      years). All patients have acceptable nasal contour and have demonstrated
      excellent nasal growth. The authors' experience demonstrates that early surgical
      intervention is an acceptable alternative for the management of nasal
      hemangiomas.

PMID- 11981189
TI  - Reverse sural artery flap: caveats for success.
AB  - Complex open wounds of the distal third of the leg and ankle remain a
      reconstructive challenge for the plastic surgeon. In many cases, these wounds are
      best addressed with a free tissue transfer. Although this group has performed
      more than 400 free flaps to the leg during the past 6 years, free tissue transfer
      can be an arduous operation that requires a team approach and substantial donor
      site morbidity for the patient. In recent years, the authors have favored the
      reverse sural artery fasciocutaneous flap in 11 patients for its ease of
      dissection, limited morbidity, and preservation of major vessels to the limb.
      Caveats for successful performance of the reverse sural artery flap include
      Doppler evidence of patent peroneal perforators, placement of a lazy T-shape skin
      paddle over the distal gastrocnemius muscle bellies, inclusion of the lesser
      saphenous vein to augment venous drainage, and, lastly, careful dissection to
      provide a wide adipofascial pedicle.

PMID- 11981190
TI  - Scar tissue flaps for the correction of postimplant breast rippling.
AB  - The author addresses rippling of the breast in patients with breast implants as a
      result of breast reconstruction or in cases of primary or secondary breast
      augmentation. The technique consists of rotating a flap of scar tissue from
      thicker parts of the breast to the thin, affected areas. The technique is simple
      both to learn and to teach. The author also discusses fat grafting in a patient
      who had severe rippling deformities in all areas of her breasts. Results of the
      fat grafting are impressively effective 3 years after correction.

PMID- 11981191
TI  - Superior positioning of the ptotic umbilicus in abdominoplasties and TRAM flaps.
AB  - The author finds that higher positioning of the umbilicus in cases of
      abdominoplasty and other similar operations such as transverse rectus abdominis
      musculocutaneous flap breast reconstruction is a useful technique. The operation
      renders better aesthetic results and also increases the margin of safety in lower
      abdominal flap circulation because tension is transferred from the lower abdomen
      to the upper abdomen. Technically, the procedure is easy to do and teach. The
      umbilicus is fixed to a higher point in the abdominal wall and the new umbilicus
      is reconstructed in a reasonably higher position with a safe degree of tension at
      the upper abdominal flap while trying to decrease tension in the lower part of
      the abdominal flap.

PMID- 11981192
TI  - Drains and seromas in TRAM flap breast reconstruction.
AB  - Surgeons who perform transverse rectus abdominis musculocutaneous (TRAM) flaps
      have differing opinions about how many drains are required in the breast and
      abdomen to prevent seroma. The authors therefore decided to review their
      experience to determine whether the number of drains influenced the incidence of
      seroma. All patients who underwent breast reconstruction using TRAM or deep
      inferior epigastric perforator flaps at The University of Texas M. D. Anderson
      Cancer Center from January 1, 1995 to June 20, 2000 and whose charts could be
      retrieved were included in the study. The number of drains used was correlated
      with the presence or absence of seroma and wound infection in both the abdomen
      and the breast. Significance was analyzed using the Chi-squared and Fisher's
      exact tests. There were 608 patients and 768 reconstructive procedures in this
      series (160 reconstructions were bilateral). Of patients who had only one drain
      in the abdomen, seroma developed in 9 patients (7.1%), whereas of those having
      two drains in the abdomen, seroma developed in only 10 patients (2.1%) (p =
      0.006). Also, of patients who had only one drain in the breast, seroma developed
      in the breast in 47 patients (9.1%), and in those with two drains, seroma
      developed in only 11 patients (4.3%) (p = 0.02). There were no significant
      differences in the infection rate in either the breast or the abdomen, although
      the trends favored a lower infection risk when two drains were used. The authors
      found that using two drains in both the abdomen and the breast can reduce the
      risk for seroma without increasing the risk for infection. This study supports
      the use of two drains in both the breast (one each beneath the TRAM flap and in
      the axilla) and abdomen (beneath the abdominoplasty flap) for patients undergoing
      breast reconstruction using the TRAM flap.

PMID- 11981193
TI  - Evaluations of the aesthetic results and patient satisfaction with the late
      pedicled TRAM flap breast reconstruction.
AB  - With the goal of evaluating the aesthetic results, testing the reliability of the
      rating systems used, and determining the patients' level of satisfaction with
      their breast reconstruction, pedicled transverse rectus abdominis
      musculocutaneous flap reconstruction was performed in 20 patients who had
      undergone mastectomy. The results were evaluated and compared 3, 6, and 12 months
      after reconstruction using the patients' own assessments (a rating of 0-10
      points) and scoring by two senior plastic surgeons (using 0-10-point global
      rating scales as well as the five subscales of the modified Garbay system). The
      interrater and intrarater agreement was poor to fair for the majority of the
      subscales. When evaluating by grades, there was significant difference (p <
      0.001) between the patients and the raters at postoperative months 3 and 6. At
      month 12, one of the raters attributed significantly lower grades (p < 0.001)
      than the patients and the other rater. The authors observed a higher level of
      satisfaction by the patients than by the raters.

PMID- 11981194
TI  - Reverse temporalis muscle flap for the reconstruction of orbital exenteration
      defects.
AB  - Orbital exenteration is a surgical procedure that results in devastating
      functional and aesthetic losses. Many reconstructive techniques, ranging from
      spontaneous epithelialization to free flaps, have been described for orbital
      exenteration defects. The temporalis muscle flap is one of the most frequently
      used flaps to obliterate the orbital cavity, but only a small portion of the
      muscle can be used for this purpose because most of the muscle is used as the
      pedicle. The reverse temporalis muscle flap based on the superficial temporal
      vessels is a versatile flap by which the entire temporalis muscle can be elevated
      and carried to defects beyond the midline. The authors have used this flap for
      orbital reconstruction after exenteration in 6 patients with successful results.
      This flap enables placement of highly vascularized tissue that provides the
      reconstructive goals of primary healing, obliterates dead space with separation
      of the orbit from the nasal cavity or sinuses, provides the potential for early
      postoperative radiotherapy, and offers possible flaps that can be used in
      combination for complex, wide defects.

PMID- 11981195
TI  - Transconjunctival upper blepharoplasty: a safe and effective addition to facial
      rejuvenation techniques.
AB  - Transconjunctival techniques for eyelid rejuvenation are now well accepted in the
      lower eyelid. Transconjunctival upper blepharoplasty is a relatively new
      technique for which overall experience has been limited. Since October 1998, the
      authors performed 42 bilateral transconjunctival upper blepharoplasties on
      patients undergoing facial and eyelid rejuvenation. They describe the essential
      anatomy and technique of the procedure. The CO2 laser is used concomitantly for
      treating fine rhytids and tightening loose upper eyelid skin. This procedure is
      an effective method of removing medial upper eyelid fat with minimal
      complications.

PMID- 11981196
TI  - Correction of cryptotia using an external stretching device.
AB  - An external stretching device was devised for the correction of cryptotia. A
      total of 27 cases of cryptotia received correction with this device. Patient age
      ranged from 10 to 40 years. During an earlier trial, patients were corrected with
      the external stretching device only. To make a definite and permanent projection
      of the upper ear, the external device had to be applied and maintained for more
      than 5 months. In some patients pin site infection developed during the
      treatment, which resulted in cessation of treatment. Recently, for cryptotia with
      marked cartilage adhesion, surgical release of the adhesion with a skin graft was
      supplemented with the application of the external stretching device. The device
      was maintained for 2 months and the long-term follow-up showed excellent outcome
      with well-maintained projection and a satisfactory auricular shape. The author
      suggests that the external stretching device is a useful alternative in the
      correction of cryptotia with severe cartilage adhesion in older children or
      adults.

PMID- 11981197
TI  - Evaluation of osteogenic/chondrogenic cellular proliferation and differentiation
      in the xenogeneic periosteal graft.
AB  - To determine whether grafted young periosteum can induce new bone formation in
      elderly patients, this preliminary study evaluated cell proliferation and
      differentiation in xenogeneic periosteal grafts in old rats radiographically,
      histologically, and immunohistochemically. Periosteum harvested from the tibia of
      young Japanese white rabbits were grafted into old Sprague-Dawley rats with or
      without administration of 1.0 mg per kilogram per day immunosuppressant FK506.
      Autogenous old periosteal tissue grafts were also evaluated as a control. Grafted
      tissue was extirpated after 7, 14, 21, and 45 days. In the xenogeneic group,
      proliferative cell nuclear antigen-positive cells were observed 7 days after
      surgery, which differentiated into chondroblasts with bone morphogenetic protein
      2 expression and finally formed cartilage by 14 days. Endochondral ossification
      was observed at 21 days, and bone replacement was completed by 45 days. No
      osteogenic cell activity was observed in the two other groups. Xenogeneic young
      periosteum thus maintained its osteogenic/chondrogenic potentiality in older
      rats.

PMID- 11981198
TI  - Pyoderma gangrenosum: a great marauder.
AB  - Pyoderma gangrenosum is a progressively necrotizing and ulcerative skin disease
      that mimics a severe bacterial infection. However, the cause is not infectious in
      nature and the lesions are refractory to local wound care and antibiotic therapy.
      The etiology of pyoderma remains unknown, although pathogenic mechanisms may
      involve immunologically mediated cutaneous damage. The authors report a 67-year
      old woman in whom a necrotic ulcer developed at a chest tube site. Treated with
      local wound care and antibiotics, this lesion spread progressively to involve 15%
      of her body surface area. A septic clinical picture developed despite sterile
      cultures, and she required several operative debridements. Her disease continued
      to spread and finally a diagnosis of pyoderma gangrenosum was considered. Treated
      with systemic steroids, hyperbaric oxygen (HBO), and local wound care, she
      eventually underwent skin grafts.

PMID- 11981200
TI  - Enterocutaneous fistula treated with a fasciocutaneous turnover flap.
AB  - A new surgical repair of enterocutaneous fistula associated with abdominal wound
      defects is presented. The authors turned over the fasciocutaneous flap from the
      surrounding skin and sutured the intestinal lumen directly to the cutaneous side
      of the flap. The method is a risk-free extraperitoneal approach that can be
      performed using local anesthesia.

PMID- 11981201
TI  - Nonhealing ulcerative mass of the elbow: do not forget tuberculosis.
AB  - Skeletal tuberculosis is a rare condition and is seen in only 1 to 2% of all
      cases of tuberculosis. The authors present a 69-year-old white woman with
      tuberculosis of the left elbow joint whose disease was suspicious for synovial
      sarcoma. Skeletal tuberculosis usually conflicts with neoplastic or inflammatory
      diseases. One should remember the possibility of bone-joint tuberculosis and send
      biopsy specimens for culture to determine the presence of acid-fast bacilli.
      However, neither culture nor polymerase chain reaction nor histological
      examination may be capable of showing the bacilli. Only a suspicion may be
      enough. The treatment protocol is usually a combination of surgical debridement
      and multidrug antituberculous chemotherapy.

PMID- 11981202
TI  - Pseudomelanoma after laser therapy.
AB  - An 18-year-old man had a melanocytic nevus on the chin that had been treated with
      three different lasers at a private clinic for 2.5 years. This lesion was excised
      and sent to a pathologist. The initial histological diagnosis was reported as
      compound nevus coexistent with changes suspicious of malignant melanoma. The
      reevaluation of histology together with the clinical information that the lesion
      had been pretreated with laser resulted in a revised diagnosis of pseudomelanoma.
      It is important to be aware of this benign pseudomelanoma, which can arise as a
      complication of laser therapy, to avoid subjecting patients to unnecessary
      surgical procedures or other forms of adjuvant treatment.

PMID- 11981203
TI  - Sir Harold Gillies and his Icelandic connection: Gillies-Millard-Dingman-Iceland:
      journey of a painting completed.

PMID- 11981204
TI  - Alphaplast.

PMID- 11981205
TI  - The southern solution to our current malaise.

PMID- 11981206
TI  - New era of liver transplantation for hepatitis B: a 17-year single-center
      experience.
AB  - OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation
      (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17
      year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection
      has been associated with aggressive reinfection and poor survival results. More
      recently, OLT outcome has been improved with the routine use of antiviral therapy
      with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV
      recurrence remains common. The authors studied the factors affecting HBV
      recurrence and outcome of transplantation, including the effects of combination
      viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of
      166 OLT recipients for chronic HBV over a 17-year period at a single center was
      performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg
      seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients,
      lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89
      (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma
      (HCC) was present in 43 patients (26%) and urgent United Network for Organ
      Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and
      multivariate analyses were performed to identify factors that affected OLT
      outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%,
      73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates
      were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%).
      When compared with a nontreated cohort, OLT recipients receiving combination
      viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence
      rates and significantly improved 1- and 3-year recurrence-free survival rates. By
      univariate estimates, patient survival was reduced in the presence of HCC, in the
      Asian population, and urgent candidates by UNOS classification. Graft loss rates
      were significantly increased in urgent OLT candidates, Asians, patients with
      pretransplant positive DNA, and in the presence of HCC. Factors that were
      significant by univariate analysis or thought to be clinically relevant were
      subjected to multivariate analysis. By multivariate estimates, urgent UNOS or
      presence of HCC adversely affected patient and graft survival rates, whereas
      combination prophylactic therapy strongly predicted improved patient and graft
      survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic
      liver transplantation for HBV under combination viral prophylaxis results in
      survival rates equivalent to other indications. Pretransplant viral replication,
      UNOS status, and the presence of HCC are all sensitive markers for
      posttransplantation outcome. Viral prophylactic therapy has effectively reduced
      HBV recurrence and prolonged survival outcomes. The combination of HBIg and
      lamivudine is the prophylactic regimen of choice.

PMID- 11981207
TI  - Gastrin-releasing peptide is a growth factor for human neuroblastomas.
AB  - OBJECTIVE: To evaluate whether gastrin-releasing peptide (GRP) and GRP receptor
      (GRP-R) expression correlate with tumor behavior and to examine the mitogenic
      actions of GRP on neuroblastomas. SUMMARY BACKGROUND DATA: Neuroblastoma is the
      most common solid tumor of infants and children. Despite recent advances in
      multimodality treatment regimens, the survival for advanced-stage tumors remains
      dismal. Neuroblastomas are known to produce GRP; however, the proliferative
      effects of GRP on neuroblastomas have not been elucidated. METHODS: Sections of
      paraffin-embedded neuroblastomas from 33 patients were analyzed for GRP and GRP-R
      protein expression by immunohistochemistry. Functional binding of GRP-R to the
      Ca2+ signaling pathway was examined. In addition, the proliferative effect of GRP
      on neuroblastoma cells (SK-N-SH, IMR-32, SH-SY5Y, LAN-1) was determined. RESULTS:
      Immunohistochemical analysis showed GRP and GRP-R protein expression in
      neuroblastomas; an increased expression of GRP-R was noted in a higher percentage
      of undifferentiated tumors compared with tumors that were benign. GRP-R mRNA was
      confirmed in neuroblastoma cell lines. GRP treatment resulted in intracellular
      calcium [Ca2+]i mobilization in two cell lines (SK-N-SH, LAN-1). GRP treatment
      stimulated growth of all four neuroblastoma cell lines; this effect was inhibited
      in SK-N-SH cells by pretreatment with GRP antibody. CONCLUSIONS: These findings
      show increased GRP-R expression in the more aggressive and undifferentiated
      neuroblastomas. The synchronous expression of GRP and its receptor, GRP-R,
      suggests a role for these proteins in tumor growth. Moreover, these findings show
      enhanced proliferation of neuroblastoma cells in vitro after GRP treatment,
      suggesting that GRP may act as an autocrine and/or paracrine growth factor for
      neuroblastomas. Treatment with specific GRP-R antagonists may provide novel
      adjuvant therapy for neuroblastomas in children.

PMID- 11981208
TI  - 100 consecutive minimally invasive Heller myotomies: lessons learned.
AB  - OBJECTIVE: To evaluate the authors' first 100 patients treated for achalasia by a
      minimally invasive approach. METHODS: Between November 1992 and February 2001,
      the authors performed 95 laparoscopic and 5 thoracoscopic Heller myotomies in 100
      patients (age 49.5 +/- 1.5 years) with manometrically confirmed achalasia. Before
      presentation, 51 patients had previous dilation, 23 had been treated with
      botulinum toxin (Botox), and 4 had undergone prior myotomy. Laparoscopic myotomy
      was performed by incising the distal 4 to 6 cm of esophageal musculature and
      extended 1 to 2 cm onto the cardia under endoscopic guidance. Fifteen patients
      underwent antireflux procedures. RESULTS: There were eight intraoperative
      perforations and only four conversions to open surgery. Follow-up is 10.8 +/- 1
      months; 75% of the patients have been followed up for at least 14 months.
      Outcomes assessed by patient questionnaires revealed satisfactory relief of
      dysphagia in 93 patients and "poor" relief in 7 patients. Postoperative heartburn
      symptoms were reported as "moderate to severe" in 14 patients and "none or mild"
      in 86 patients. Fourteen patients required postoperative procedures for continued
      symptoms of dysphagia after myotomy. Esophageal manometry studies revealed a
      decrease in lower esophageal sphincter pressure (LESP) from 37 +/- 1 mm Hg to 14
      +/- 1 mm Hg. Patients with a decrease in LESP of more than 18 mm Hg and whose
      absolute postoperative LESP was 18 or less were more likely to have relief of
      dysphagia after surgery. Thirty-one patients who underwent Heller alone were
      studied with a 24-hour esophageal pH probe and had a median Johnson-DeMeester
      score of 10 (normal <22.0). Mean esophageal acid exposure time was 3 +/- 0.6%
      (normal 4.2%). Symptoms did not correlate with esophageal acid exposure.
      CONCLUSIONS: The results after minimally invasive treatment for achalasia are
      equivalent to historical outcomes with open techniques. Satisfactory outcomes
      occurred in 93% of patients. Patients whose postoperative LESP was less than 18
      mm Hg reported the fewest symptoms. After myotomy, patients rarely have abnormal
      esophageal acid exposure, and the addition of an antireflux procedure is not
      required.

PMID- 11981209
TI  - Results of 281 consecutive total laparoscopic Roux-en-Y gastric bypasses to treat
      morbid obesity.
AB  - OBJECTIVE: To determine the safety and efficacy of laparoscopic Roux-en-Y gastric
      bypass for the treatment of morbid obesity. SUMMARY BACKGROUND DATA: Laparoscopic
      Roux-en-Y gastric bypass is a new and technically challenging surgical procedure
      that requires careful study. METHODS: The authors attempted total laparoscopic
      Roux-en-Y gastric bypass in 281 consecutive patients. Procedures included 175
      proximal bypasses, 12 long-limb bypasses, and 9 revisional procedures from
      previous bariatric operations. The gastrojejunostomy and jejunojejunostomy were
      primarily constructed using linear stapling techniques. RESULTS: Eight patients
      required conversion to an open procedure (2.8%). The mean age of the patients was
      41.6 years (range 15-71) and 87% were female. The mean preoperative body mass
      index was 48.1 kg/m2. The operative time decreased significantly from 234 +/- 77
      minutes in the first quartile to 162 +/- 42 minutes in the most recent quartile.
      Postoperative length of stay averaged 4 days (range 2-91), with 75% of patients
      discharged within 3 days. The median hospital stay was 2 days. No patient died
      after surgery. Complications included three (1.5%) major wound infections (each
      followed a reoperation for a complication or open conversion), incisional hernia
      in 5 patients (1.8%), and anastomotic leak with peritonitis in 14 patients
      (5.1%). Three gastrojejunal leaks were managed without surgery, four by
      laparoscopic repair/drainage, and three by open repair/drainage. Only three
      patients had anastomotic leaks in the most recent 164 procedures (1.8%) since the
      routine use of a two-layer anastomotic technique. Data at 1 year after surgery
      were available in 69 of 96 (72%) patients (excludes revisions). Weight loss at
      one year was 70 +/- 5% of excess weight. Most comorbid conditions resolved by 1
      year after surgery; notably, 88% of patients with diabetes no longer required
      medications. CONCLUSIONS: Laparoscopic gastric bypass demonstrates excellent
      weight loss and resolution of comorbidities with a low complication rate. The
      learning curve is evident: operative time and leaks decreased with experience and
      improved techniques. The primary advantage is an extremely low risk of wound
      complications, including infection and hernia.

PMID- 11981210
TI  - Gastrointestinal manifestations of multiple endocrine neoplasia type 2.
AB  - OBJECTIVE: To determine the clinical features, natural history, and role of
      surgery for gastrointestinal manifestations of the multiple endocrine neoplasia
      type 2 (MEN 2) syndromes. SUMMARY BACKGROUND DATA: The MEN 2 syndromes are
      characterized by medullary thyroid carcinoma and other endocrinopathies. In
      addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all
      patients with MEN 2B have intestinal neuromas and megacolon that can cause
      significant gastrointestinal problems. METHODS: From 83 families with MEN 2A,
      eight patients with HD were identified (MEN 2A-HD). These and all patients with
      MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to
      describe the onset and type of gastrointestinal symptoms and treatment they had
      before the diagnosis of MEN 2. Records of all patients responding were reviewed,
      including radiographic imaging, histology, surgical records, and genetic testing.
      RESULTS: Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28)
      to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to
      63 years before being diagnosed with MEN 2. All patients responding were
      underweight as infants and had symptoms of abdominal pain, distention, and
      constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had
      intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal
      biopsies with a diverting colostomy as the initial surgical procedure. This was
      followed by a colostomy takedown and pull-through procedure at a later interval.
      Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to
      24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%),
      abdominal distention or being underweight as a child (64%), abdominal pain (54%),
      constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%).
      Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had
      radiographic imaging, 32% were admitted to the hospital, and 29% underwent
      surgery. CONCLUSIONS: Patients with MEN 2A-HD had a typical HD presentation and
      always required surgery. Patients with MEN 2B have significant gastrointestinal
      symptoms, but less than a third had surgical intervention. Understanding the
      clinical course and differences in these patients will improve clinical
      management.

PMID- 11981211
TI  - Implications of follicular neoplasms, atypia, and lesions suspicious for
      malignancy diagnosed by fine-needle aspiration of thyroid nodules.
AB  - OBJECTIVE: To break out subcategories of atypical and suspicious cytologic
      interpretations of thyroid aspirations and correlate those with final histologic
      diagnosis. SUMMARY BACKGROUND DATA: Fine-needle aspiration (FNA) of thyroid
      nodules has become the primary diagnostic tool in the initial evaluation of
      thyroid nodules. Management of thyroid nodules is based on statistical data
      correlating a specific cytologic reading with the probability of malignancy. Two
      particular cytologic readings that frustrate both cytopathologists and surgeons
      are follicular neoplasms and cells that show atypia. In most reported series,
      follicular neoplasms and cells showing atypia are included in a broad
      "suspicious" category, with reported overall malignancy rates generally between
      20% and 30%. However, there is interest in determining whether these suspicious
      lesions can be subcategorized, allowing a more accurate assessment of the risk of
      malignancy. In addition, there is recent evidence that the incidence of
      follicular cancer may be declining in this country, possibly decreasing the
      probability that a "follicular neoplasm" will prove to be a follicular cancer.
      METHODS: From January 1994 through December 2000, 709 thyroid FNAs were performed
      at a single institution. Those interpreted as suspicious and the subsequent
      histologic reports were reviewed. From this set, four specific categories were
      defined, and the clinical records for patients whose cytology matched these
      categories form the subject of this study. These four categories are follicular
      neoplasms without atypia, follicular neoplasms with atypia, atypia, and
      suspicious for malignancy. In addition, lesions with nondiagnostic cytology were
      reviewed. Only lesions for which there was histologic follow-up were considered.
      RESULTS: Ninety-eight aspirates were categorized as follicular neoplasms without
      atypia, follicular neoplasms with atypia, or atypia alone. Of 74 follicular
      neoplasms without atypia, only 5 (6.8%) were malignant, and none of these were
      follicular thyroid cancers. Nine of the lesions were follicular neoplasms with
      atypia, and four (44.4%) of these were malignant, including two that were
      invasive follicular cancers. Of 15 lesions showing atypia alone, 3 (20%) were
      malignant, all of which were papillary thyroid cancers. Twenty-five additional
      patients had lesions highly suspicious for malignancy. Twenty-one (84%) of these
      lesions were malignant, the majority being papillary thyroid cancers. Only one
      was a follicular cancer. Fifty patients with nondiagnostic cytology had
      subsequent action taken. Thirty-one of these lesions were resected, with five
      (16.1%) proving to be malignant. CONCLUSIONS: Thyroid nodules whose FNA is
      diagnosed as highly suspicious for malignancy should be resected unless there are
      significant contraindications to a surgical procedure. The extremely low rate
      (2%) of invasive follicular cancers among all follicular neoplasms may reflect
      changing histologic criteria for follicular carcinoma, a true change in the
      disease frequency, or both. For thyroid nodules whose cytology shows a follicular
      neoplasm without atypia, malignancy rates of 8% or less may allow nonsurgical
      options, including reevaluation in selected populations. Continued efforts to
      correlate malignancy rates to specific cytologic criteria will allow patients to
      make more informed decisions regarding their medical care.

PMID- 11981212
TI  - Six hundred fifty-six consecutive explorations for primary hyperparathyroidism.
AB  - OBJECTIVE: To review the outcomes of 656 consecutive parathyroid explorations
      performed by a single surgeon and to compare the results of conventional and
      minimally invasive parathyroidectomy (MIP) techniques. SUMMARY BACKGROUND DATA:
      Traditional surgery for primary hyperparathyroidism (HPTH) involves bilateral
      cervical exploration, which is usually accomplished under general endotracheal
      anesthesia. The MIP technique involves preoperative localization with sestamibi
      scans, surgeon-administered cervical block anesthesia, directed exploration
      through a small incision, intraoperative rapid parathyroid hormone assay, and
      discharge within 2 to 3 hours of surgery. METHODS: Six hundred fifty-six
      consecutive patients with primary HPTH underwent exploration between January 1990
      and March 2001. RESULTS: MIP was used with ever-increasing frequency beginning in
      March 1998. Four hundred one procedures (61%) were performed using the standard
      technique and 255 patients (39%) were selected for MIP. The success rate for the
      entire series was 98%, with no significant differences comparing traditional and
      MIP techniques. The overall complication rate of 2.3% reflects 3.0% and 1.2%
      rates in the standard and MIP groups, respectively. MIP was associated with
      approximately a 50% reduction in operating time, a sevenfold reduction in length
      of hospital stay, and a mean cost savings of $2,693 per procedure, which
      represents nearly a 50% reduction in total hospital charges. CONCLUSIONS: A
      dramatic and sustained shift has occurred in the surgical treatment of primary
      HPTH: MIP has replaced traditional exploration for most patients.

PMID- 11981213
TI  - Long-term follow-up of patients with tertiary hyperparathyroidism treated by
      resection of a single or double adenoma.
AB  - OBJECTIVE: To determine whether patients with tertiary hyperparathyroidism due to
      single- or two-gland disease undergoing limited resection have similar long-term
      outcomes compared with patients with hyperplasia undergoing subtotal or total
      parathyroidectomy. SUMMARY BACKGROUND DATA: Tertiary hyperparathyroidism occurs
      in less than 2% of patients after renal transplantation. Approximately 30% of
      these cases are caused by one or two hyperfunctioning glands. Nevertheless, the
      standard operation for this disease has been subtotal or total parathyroidectomy
      with autotransplantation. METHODS: Seventy-one patients underwent surgery for
      tertiary hyperparathyroidism. At the time of surgery, 19 patients who had a
      single or double adenoma underwent limited resection of the enlarged glands only
      (adenoma group). The remaining 52 patients with three- or four-gland hyperplasia
      had subtotal or total parathyroidectomy with implantation (hyper group). Long
      term cure rates between the two groups were compared. RESULTS: In the adenoma
      group, 7 patients had a single adenoma and 12 underwent resection of a double
      adenoma. In the hyper group, 49 patients had subtotal and 3 had total
      parathyroidectomies. After surgery, 70 of 71 patients (99%) were cured of their
      hypercalcemia. The incidence of postoperative transient hypocalcemia was
      significantly higher in the hyper group (27% vs. 5%). No patients in either group
      had permanent hypocalcemia requiring long-term supplementation. With up to 16
      years of follow-up, there have been no recurrences in the adenoma group, whereas
      three patients (6%) in the hyper group have had recurrent or persistent
      hyperparathyroidism. CONCLUSIONS: Patients with tertiary hyperparathyroidism who
      underwent limited resection of a single or double adenoma only had equivalent
      long-term cure rates compared with patients undergoing more extensive resections.
      Therefore, the authors recommend in patients with tertiary hyperparathyroidism
      and enlargement of only one or two parathyroid glands that the resection be
      limited to these abnormal glands only.

PMID- 11981214
TI  - Three hundred consecutive emergent celiotomies in general surgery patients:
      influence of advanced diagnostic imaging techniques and procedures on diagnosis.
AB  - OBJECTIVES: To assess the utility of advanced tests performed before surgery on
      patients who needed emergent abdominal operations, and to assess the outcomes of
      these patients relative to their diagnoses. SUMMARY BACKGROUND DATA: Patients
      with a potential abdominal catastrophe may have various presentations,
      contributing to the difficulty of the decision about whether an operation is
      indicated. Advanced tests can be valuable, but the use of these adjuncts should
      be appropriate to the clinical status of the patient so that treatment is not
      delayed. The role of these tools in the evaluation of the patient who may need an
      emergent abdominal operation is less well defined. METHODS: Data were reviewed on
      adult patients undergoing emergent abdominal operations. Entrance criteria
      included patients who had an emergent abdominal operation, defined as one
      performed for presumed gastrointestinal perforation, infarction, or hemorrhage
      within 6 hours of admission or surgical consultation. Advanced tests were those
      that were time-consuming or invasive or required scheduling with other
      departments so that the risk/benefit ratio of these tests could be questioned. A
      useful test was one that provided information that contributed to a change in the
      patient's management. RESULTS: During a 5-year period, 300 consecutive adult
      patients (158 perforations, 66 hemorrhage, 53 ischemia/infarction, and 23
      "other") underwent emergent nontrauma celiotomies. Overall, the death rate was
      20%. Advanced preoperative tests were performed in 135 (45%) of the 300 patients,
      and 40 of these patients had delayed treatments. Preoperative localization of
      bleeding sites was accomplished in 77% of patients with upper gastrointestinal
      bleeding and 86% of patients with lower gastrointestinal bleeding. CONCLUSIONS:
      Most patients in need of emergent abdominal operations should not undergo
      advanced tests. The primary role of advanced tests in these patients is in the
      localization of a bleeding site. With the exception of patients who present with
      hemorrhage, advanced tests frequently cause a delay in treatment.

PMID- 11981215
TI  - Thirty-day postoperative death rate at an academic medical center.
AB  - OBJECTIVE: To improve understanding of perioperative deaths at an academic
      medical center. SUMMARY BACKGROUND DATA: Because published data have typically
      focused on specific patient populations, diagnoses, or procedures, there are few
      data regarding surgical deaths and complications in institutional or regional
      studies. Specifically, surgical adverse events and errors are generally not
      studied comprehensively. This limits the overall understanding of complications
      and deaths. METHODS: Data from all operations performed in the main operating
      suite of the University of Virginia Health Sciences Center from January 1 to June
      30, 1999, were compared with state death records to gain a dataset of patients
      dying within 30 days of surgery. All clinical records from patients who died were
      screened for adverse events and subsequently reviewed by three surgeons who
      identified adverse events and errors and performed comparisons with survivors.
      RESULTS: One hundred nineteen deaths followed 7,379 operations performed on 6,296
      patients, yielding a patient death rate of 1.9%. Patients dying within 30 days of
      surgery were older and had higher American Society of Anesthesiologists scores.
      Of 119 deaths, 86 (72.3%) were attributable to the patient's primary disease.
      Twenty-three patient deaths (19.3% of all deaths, 0.37% of all patients) could
      not be attributed to the patient's primary disease and thus were suspicious for
      an adverse event (AE) as the cause of the death. Of the 23 deaths suspicious for
      AE, 15 (12.6% of all deaths, and 65.2% of AE deaths) followed an error in care
      and thus were classified as potentially preventable, affecting 0.24% of the study
      population. CONCLUSIONS: Overall, the 30-day postoperative death rate was low in
      the total surgical population at an academic medical center. Errors and AEs were
      associated with 12.6% and 19.3% of deaths, respectively. Retrospective review
      inadequately characterized the nature of AEs and failed to determine causality.
      Prospective audits of outcomes will enhance our understanding of surgical AEs.

PMID- 11981216
TI  - Treatment-related outcomes from blunt cerebrovascular injuries: importance of
      routine follow-up arteriography.
AB  - OBJECTIVE: To assess the impact of routine follow-up arteriography on the
      management and outcome of patients with acute blunt cerebrovascular injuries
      (BCVI). SUMMARY BACKGROUND DATA: During the past 5 years there has been
      increasing recognition of BCVI, but the management of these lesions remains
      controversial. The authors previously proposed a grading system for BCVI, with
      grade-specific management guidelines. The authors have noted that a significant
      number of injuries evolve within 7 to 10 days, warranting alterations in therapy.
      METHODS: A prospective database of a regional trauma center's experience with
      BCVI has been maintained since 1990. A policy of arteriographic screening for
      BCVI based on injury mechanism (e.g., cervical hyperextension) and injury
      patterns (e.g., cervical and facial fractures) was instituted in 1996. A grading
      system was devised to develop management protocols: I = intimal irregularity; II
      = dissection/flap/thrombus; III = pseudoaneurysm; IV = occlusion; V =
      transection. RESULTS: From June 1990 to October 2001, 171 patients (115 male, age
      36 +/- 1 years) were diagnosed with BCVI. Mean injury severity score was 28 +/-
      1; associated injuries included brain (57%), spine (44%), chest (43%), and face
      (34%). Mechanism was motor vehicle crash in 50%, fall in 11%, pedestrian struck
      in 11%, and other in 29%. One hundred fourteen patients had 157 carotid artery
      injuries (43 bilateral), and 79 patients had 97 vertebral artery injuries (18
      bilateral). The breakdown of injury grades was 137 grade I, 52 grade II, 32 grade
      III, 25 grade IV, and 8 grade V. One hundred fourteen (73%) carotid and 65 (67%)
      vertebral arteries were restudied with arteriography 7 to 10 days after the
      injury. Eight-two percent of grade IV and 93% of grade III injuries were
      unchanged. However, grade I and II lesions changed frequently. Fifty-seven
      percent of grade I and 8% of grade II injuries healed, allowing cessation of
      therapy, whereas 8% of grade I and 43% of grade II lesions progressed to
      pseudoaneurysm formation, prompting interventional treatment. There was no
      significant difference in healing or in progression of injuries whether treated
      with heparin or antiplatelet therapy or untreated. However, heparin may improve
      the neurologic outcome in patients with ischemic deficits and may prevent stroke
      in asymptomatic patients. CONCLUSIONS: Routine follow-up arteriography is
      warranted in patients with grade I and II BCVIs because most of these patients
      (61% in this series) will require a change in management. A prospective
      randomized trial will be necessary to identify the optimal treatment of BCVI.

PMID- 11981217
TI  - Repair of full-thickness defects in alimentary tract wall with patches of
      expanded polytetrafluoroethylene.
AB  - OBJECTIVES: To test the efficacy of patches of expanded polytetrafluoroethylene
      (ePTFE) for the repair of full-thickness defects in alimentary tract wall.
      SUMMARY BACKGROUND DATA: A recent report of successful replacement of duodenal
      wall with patches of ePTFE was met with skepticism and clearly warranted
      confirmation as well as evaluation in repair of other segments of the abdominal
      intestinal tract. METHODS: Defects of 4 cm2 were created in various segments of
      canine abdominal alimentary tract (stomach, duodenum, small bowel, and colon) as
      well as in bladder dome. For the duodenum in 13 dogs, three different ePTFE
      fabrications were used: CVX (cardiovascular), PDX (preclude dura membrane), and
      DLM (dual mesh plus). In repair of the other areas in six dogs, the PDX patch was
      used. When the animals were killed, both gross inspection of the parietes and
      tissue for histologic study became the basis for evaluation. Peritoneal and
      intraluminal cultures of the specific study viscera were also taken. RESULTS:
      There were no patch failures. Only six significant adhesions were noted in 3 of
      the 19 dogs. Serosal surface healing was complete without exception by 1 week in
      all animals. Patches of CVX and PDX had heaping mucosa at the margin of well
      sealed patch edges in the study involving duodenum. However, the DLM patch had an
      undergrowth of mucosa with partial patch separation by 1 week, beginning patch
      extrusion into gut lumen at 3 weeks, and total separation of patch with complete
      mucosal repair at 6 weeks. The fate of the PDX patches at 6 weeks in stomach,
      small bowel, colon, and bladder was identical to what had been observed for the
      PDX patch in the duodenum. All peritoneal and bladder cultures had no growth,
      whereas the contents of the alimentary tract grew expected flora. CONCLUSIONS:
      These observations suggest that ePTFE may well be an acceptable membrane for at
      least temporary replacement of full-thickness hollow viscus defects, even in the
      face of heavy bacterial contamination, and that certain structural configurations
      of ePTFE may provide a base for increasing absorptive mucosal surface area.

PMID- 11981218
TI  - Adrenalectomy for familial pheochromocytoma in the laparoscopic era.
AB  - OBJECTIVE: To report the results of treatment of patients with familial
      pheochromocytomas in the laparoscopic era. SUMMARY BACKGROUND DATA: The optimal
      surgical management of pheochromocytomas that arise in familial neoplasia
      syndromes may be complicated by bilateral involvement and associated
      endocrinopathies. METHODS: Twenty-one patients with familial pheochromocytomas
      (15 with multiple endocrine neoplasia [MEN] 2A, 4 with MEN 2B, 1 each with von
      Hippel-Lindau and neurofibromatosis type 1) underwent adrenalectomy between
      December 1993 and July 2001. Clinical, biochemical, and pathologic data were
      obtained by retrospective review of perioperative medical records, postoperative
      biochemical testing, and patient questionnaire. RESULTS: Mean age at diagnosis
      was 37 +/- 11 years. Twenty of the 21 patients had elevated urine catecholamines,
      and all had radiographic evidence of an adrenal tumor or tumors. Pheochromocytoma
      related symptoms were present in 11 patients (52%). One patient with MEN 2B
      underwent open adrenalectomy due to previous adrenal surgery and megacolon.
      Laparoscopic adrenalectomy was attempted in the remaining 20 patients (9 right,
      11 left, 2 bilateral). Two patients (9.1%) were converted to open adrenalectomy.
      Intraoperative hypertensive episodes occurred in 15 patients (71%) and were
      easily controlled medically. Mean operative time was 216 +/- 57 minutes, mean
      postoperative length of stay was 3.1 +/- 1.3 days, and mean tumor size was 3.1 +/
      1.0 cm. Minor complications occurred in three patients (14.3%) and major
      complications in two patients (9.5%). During a mean follow-up of 57 months, a
      contralateral pheochromocytoma developed in four patients with MEN 2 (33%); three
      of them underwent adrenalectomy. There have been no long-term complications
      related to hypertension or adrenalectomy. CONCLUSIONS: This study is the largest
      series of patients with familial pheochromocytoma undergoing adrenalectomy during
      the laparoscopic era. The results suggest that the laparoscopic approach is safe
      and effective for managing unilateral or bilateral adrenal medullary disease in
      this population.

PMID- 11981219
TI  - Preoperative predictors of survival after resection of small hepatocellular
      carcinomas.
AB  - OBJECTIVE: To determine preoperative predictors of survival that can guide the
      choice of treatment for patients with small hepatocellular cancers (HCCs).
      SUMMARY BACKGROUND DATA: The treatment of patients with small (</=5 cm in
      diameter) HCCs is controversial. METHODS: A cohort of 249 patients (69 women, 180
      men; median age 62 years) who underwent resection with curative intent for small
      HCC was identified from a multiinstitutional database. For each patient, the
      clinical data and pathology slides were reviewed. Six clinical factors (age,
      gender, preoperative alpha-fetoprotein level, hepatitis serology, number of
      tumors [single vs. multiple], and Child-Pugh score) and three pathologic factors
      (hepatitis activity score, fibrosis score, and Edmondson-Steiner tumor grade)
      that can be determined before surgery were correlated with survival. Log-rank
      tests and Cox proportional hazards modeling were used to determine factors
      influencing survival. RESULTS: The median overall survival for the entire cohort
      was 4.2 years. The estimated overall 5- and 8-year survival rates were 41.1% and
      19.8%, respectively. Multivariate Cox analysis indicated that fibrosis score,
      Edmondson-Steiner grade, and Child-Pugh score were simultaneously significant
      predictors of survival after resection. A prognostic scoring system based on
      these covariates was derived and applied to the entire cohort. Patients lacking
      all three risk factors were assigned a score of 1, patients with one risk factor
      were assigned a score of 2, and patients with two or three risk factors were
      assigned a score of 3. Pairwise log-rank tests indicated significant differences
      in survival between scores 1 and 2, scores 2 and 3, and scores 1 and 3. This
      scoring system retained its prognostic significance when a subset of 98 patients
      with positive hepatitis C serology was analyzed separately. CONCLUSIONS: Patients
      with small HCCs who will derive the least benefit from resection can be
      identified before surgery using a score based on tumor grade and the severity of
      underlying liver disease. In these patients, transplantation and/or ablation
      should be considered as possible alternative therapies.

PMID- 11981222
TI  - The effect of zolpidem on operant behavior and its relation to pharmacokinetics
      after intravenous and subcutaneous administration: concentration-effect
      relations.
AB  - We characterized the effects of i.v. and s.c. zolpidem (1-8 mg/kg) under a
      differential reinforcement of low-rate schedule (i.e. DRL 45 s) in 3-hour
      sessions. Both behavioral and pharmacokinetic-pharmacodynamic analyses were used
      with the intent to compare the effects of zolpidem with those of benzodiazepines
      reported previously under the same behavioral paradigm. Zolpidem increased the
      shorter-response [inter-response times (IRTs)<45 s] rate and decreased the
      reinforcement rate in a dose- and time-related fashion. The behavioral profiles
      of zolpidem were mainly similar to those of benzodiazepines, except zolpidem
      produced far fewer shorter IRT responses. Pharmacokinetically, zolpidem decays
      biexponentially with distributional and terminal elimination half-lives of 5.2
      and 42 min, respectively. The absorption rate constant and absolute
      bioavailability for s.c. zolpidem were 0.083/min and of 84.1%, respectively. The
      pharmacodynamic parameters for the reinforcement rate, an index of timing
      performance, were determined by integration of behavioral and pharmacokinetic
      profiles in a between-subject design using the effect-linked inhibitory sigmoidal
      E(max) model. The pharmacokinetic-pharmacodynamic analysis revealed that the
      potency of zolpidem (concentration required to produce 50% maximal effects,
      IC(50)) in disrupting the timing performance was 0.129 microg/ml. The
      pharmacodynamic estimates of zolpidem were compared to our previous results for
      benzodiazepines.

PMID- 11981220
TI  - Prospective study of eukaryotic initiation factor 4E protein elevation and breast
      cancer outcome.
AB  - OBJECTIVE: To validate the authors' initial hypothesis-generating observation
      that eukaryotic initiation factor 4E (eIF4E) protein elevation predicts a higher
      cancer recurrence rate in patients with stage 1 to 3 breast cancer. SUMMARY
      BACKGROUND DATA: Tumor size and nodal status continue to be the two most
      important independent prognostic markers in breast cancer, despite well
      documented limitations. In a previous smaller retrospective study, eIF4E,
      important in the regulation of protein synthesis of mRNAs with long or complex 5'
      untranslated regions, appeared promising as an independent predictor of breast
      cancer recurrence. METHODS: Specimens and clinical data from 191 patients with
      stage 1 to 3 breast cancer were accrued prospectively. Data collected include
      stage of disease, tumor grade, age at diagnosis, and menopausal status. Endpoints
      measured were disease recurrence and cancer-related death. eIF4E protein level
      was quantified using Western blot analysis. Immunohistochemical staining was used
      to determine estrogen receptor, progesterone receptor, and HER-2/neu receptor
      status. Statistical analysis include Cox proportional hazards model, log-rank
      test, Kaplan-Meier survival curve, Fisher exact test, and t test. RESULTS:
      Patients were divided into three groups based on tertile distribution of eIF4E:
      low, defined as less than 7.5-fold elevation (n = 64); intermediate, defined as
      7.5- to 14-fold elevation (n = 61); and high, defined as more than 14-fold
      elevation (n = 66). The relative risk for cancer recurrence with intermediate
      elevation was 4.1 times that of patients with low elevation. For patients with
      high elevation, the relative risk for recurrence was higher, at 7.2 times that of
      the low group. The relative risk for cancer-related death for high elevation was
      7.3 times that of patients with low eIF4E. Using multivariate analysis, high
      eIF4E remained an independent predictor of cancer recurrence after adjusting for
      tumor size, tumor grade, nodal disease, estrogen receptor status, progesterone
      receptor status, and menopausal status. CONCLUSIONS: High eIF4E is an independent
      predictor of cancer recurrence in patients with stage 1 to 3 breast cancer. The
      relative risk for cancer recurrence increases with eIF4E protein elevation. High
      eIF4E elevation is also associated with an increased relative risk for cancer
      related death.

PMID- 11981223
TI  - Acute behavioral and physiological effects of modafinil in drug abusers.
AB  - Modafinil, a novel stimulant, is effective in the treatment of excessive daytime
      sleepiness associated with narcolepsy. It is biochemically and pharmacologically
      distinct from prototypical stimulants such as D-amphetamine, cocaine, and
      methylphenidate. The present experiment was designed to assess the acute
      behavioral effects of oral modafinil, cocaine, and placebo in participants (n=9)
      with recent histories of cocaine use (i.e. positive urine for cocaine or
      benzoylecgonine during the initial screening interview). Drug effects were
      assessed with a battery of self-reported drug-effect questionnaires, performance
      measures, and physiological indices. Cocaine, but not modafinil, produced
      stimulant-like self-reported drug effects (e.g. increased ratings of High and
      Stimulated). Modafinil and cocaine dose-dependently increased heart rate and
      blood pressure. The results of the present study suggest that modafinil has
      minimal abuse potential, but should be viewed cautiously because of the
      relatively small sample size. Future studies should further characterize the
      abuse potential of modafinil using other behavioral arrangements, such as drug
      discrimination or drug self-administration. A full characterization of the abuse
      potential of modafinil will become important as the use of this drug increases.

PMID- 11981224
TI  - The effects of simultaneous administration of alpha(2) -adrenergic agents with L
      NAME or L-arginine on the development and expression of morphine dependence in
      mice.
AB  - Both alpha(2)-adrenoceptors and the L-arginine/nitric oxide (NO) pathway have
      been implicated in the modulation of morphine dependence. This study examined the
      effects of simultaneous administration of the alpha(2)-adrenoceptor agonist
      clonidine or the antagonist yohimbine together with the NO precursor L-arginine
      or the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on
      the induction and expression of morphine dependence as assessed by naloxone
      precipitated withdrawal jumping and diarrhoea. Male NMRI mice weighing 20-30 g
      were used. In the induction phase, clonidine (0.01-0.1 mg/kg) intensified and
      yohimbine (0.5-2 mg/kg) attenuated the degree of morphine dependence. Yohimbine
      reversed the effect of clonidine. L-NAME (5 and 10 mg/kg) did not affect the
      development of morphine dependence, but significantly potentiated the effects of
      both subeffective (0.01 mg/kg) and effective (0.03 mg/kg) doses of clonidine. L
      Arginine did not alter morphine dependence but inhibited the effect of clonidine.
      The effects of yohimbine in the induction phase were attenuated by L-NAME, but
      were not significantly affected by L-arginine. In the expression phase, clonidine
      attenuated and yohimbine intensified the signs of dependence. The effect of
      clonidine was inhibited by yohimbine. In the expression phase, L-NAME attenuated
      the withdrawal syndrome at 10 mg/kg and showed potentiation with clonidine in
      suppressing withdrawal signs. L-Arginine did not alter morphine dependence, but
      at 20 mg/kg inhibited and at 100 mg/kg potentiated the attenuating effect of
      clonidine on the expression of withdrawal syndrome. The effect of yohimbine on
      the expression phase was also attenuated by L-NAME, but was not significantly
      affected by L-arginine. In conclusion, alpha(2)-adrenergic and NO pathways seem
      to be functionally linked in the modulation of opioid dependence.

PMID- 11981225
TI  - Effect of repeated treatment with tianeptine and fluoxetine on central dopamine
      D(2) /D(3) receptors.
AB  - Tianeptine (TIA) is an antidepressant drug that has been shown to decrease
      extracellular serotonin level and reveals no affinity for neurotransmitter
      receptors. The present study was aimed at determining whether repeated TIA
      treatment induced any adaptive changes in the central dopamine D(2)/D(3) system
      (behavioural and biochemical) similar to those reported earlier for tricyclic
      antidepressants. Experiments were carried out on male Wistar rats. TIA was
      administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14
      days). Fluoxetine (FLU), used as a reference compound, was also administered at a
      dose of 10 mg/kg. The results obtained showed that TIA or FLU administered
      repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy
      dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the
      [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU
      in the islands of Calleja minor, as well as in the shell part of nucleus
      accumbens septi. On the other hand, both TIA and FLU administered repeatedly
      increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the
      nucleus caudatus as well as in the core part of the nucleus accumbens septi.
      Similar effects have been observed when dopamine D(2)/D(3) receptors were
      visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor
      antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding
      for dopamine D(2) receptors, not only after repeated but also after acute
      treatment. These results indicate that repeated TIA and FLU administration
      induces adaptive changes in the dopaminergic D(2)/D(3) system and especially
      enhances the functional responsiveness of dopamine D(2) and D(3) receptors.
      However, the question of whether this increased responsiveness is important for
      clinical antidepressant efficacy remains open.

PMID- 11981226
TI  - Elevated T-maze as an animal model of memory: effects of scopolamine.
AB  - The elevated T-maze (ETM) is a putative model for the assessment of anxiety and
      memory in rodents. This study was designed to further evaluate the utility of the
      ETM in the study of memory processes. We compared the performance of rats in the
      ETM, the water maze (WM) and the two-way avoidance task (TWA), after pretreatment
      with scopolamine (SCO; 0.3 or 1.2 mg/kg i.p.). In the ETM, rats were first
      trained to meet the criterion of remaining inside the enclosed arm for 300
      seconds. Seventy-two hours after training, a retrieval test session was
      performed. At the lower dose, SCO impaired performance in the retrieval session
      on all three tasks, whereas in the training session an effect was noted only on
      the WM task. At the higher dose, SCO impaired the performance of rats in the
      training sessions for ETM and WM, but not TWA. In a fourth experiment using the
      elevated plus-maze, SCO showed anxiolytic-like effects at the higher dose only.
      In conclusion, the effects of SCO in rats submitted to the ETM were dose
      dependent, with the lower dose exerting a selective effect detected only on
      retrieval, whereas the higher dose induced motor effects that disrupted
      inhibitory avoidance acquisition, resulting in impaired retrieval. The results
      are discussed in terms of the utility of the ETM in the study of drug effects and
      the neurobiological mechanisms underlying anxiety, learning and memory.

PMID- 11981227
TI  - Evidence for the involvement of the muscarinic cholinergic system in the central
      actions of pentoxifylline.
AB  - This study shows that pentoxifylline (ptx), a xanthine derivative, significantly
      attenuates scopolamine-induced memory impairment in rats, as demonstrated in a
      passive avoidance task (50 mg/kg intraperitoneally [i.p.]) and in an elevated T
      maze (10 and 50 mg/kg i.p.). Ptx (25, 50 and 100 mg/kg i.p.) also potentiates
      oxotremorine-induced tremors in mice, in a dose-dependent manner, and this effect
      was completely prevented by atropine. In addition, ptx (50 and 100 mg/kg i.p.)
      increased the number of animals developing pilocarpine-induced seizures, and
      potentiated the latency to the first pilocarpine-induced convulsion. Hippocampus
      homogenates from rats treated with ptx (100 mg/kg) for 1 week and sacrificed 15
      min after the last injection showed a significant decrease in the muscarinic
      receptor numbers, indicative of a downregulation phenomenon. Similar effects were
      observed when assays were performed 24 h after the last ptx injection (10 and 50
      mg/kg i.p.), but not after 72 h. Additionally, in vitro assays showed that ptx
      inhibits acetylcholinesterase activity in a dose-dependent manner when incubated
      with homogenates from rat hippocampus. Our data suggest that the muscarinic
      agonist effect of ptx could possibly depend on factors such as endogenous
      cholinergic activity.

PMID- 11981228
TI  - Effects of cocaine on responding for ethanol or sucrose under a progressive ratio
      schedule.
AB  - Progressive ratio (PR) schedules have been increasingly used to study motivation
      for self-administered drugs of abuse, such as psychostimulants and ethanol. In
      these and other studies, the breaking point (BP) is thought to be a measure of
      the motivation of the animal to work for a particular reward. Ethanol, a highly
      abused drug, maintains only low BPs. The present experiment was designed to
      examine if the low BP achieved by animals working for ethanol could be increased
      by the administration of a psychostimulant. A group working for a sucrose
      reinforcer was included for comparison. Rats previously trained to lever press
      under a PR schedule for 0.1 ml aliquots of 10% ethanol or 5% sucrose reinforcers
      were dosed once a week with cocaine (0, 5 and 15 mg/kg intraperitoneally) 30 min
      prior to their daily operant session using a Latin square design. Vehicle and 5
      mg/kg cocaine had no effect on BP for any reinforcer, but 15 mg/kg cocaine
      produced a significantly higher BP (P<0.05) for animals working for either
      ethanol or sucrose. The same doses of cocaine decreased consumption of, and
      preference for, a 5% sucrose solution. These results indicate that, although
      cocaine administration does not increase sucrose preference, it may increase BP
      values in PR schedules. It is therefore unlikely that the increases in BP reflect
      cocaine-induced increased motivation, and they may be due to cocaine's stimulant
      or other properties. These data reinforce opinions that PR schedules may be
      unsuitable for assessing the effects of experimental manipulations on motivation
      for drugs with stimulant actions.

PMID- 11981229
TI  - Modulation of working memory and of long- but not short-term memory by
      cholinergic mechanisms in the basolateral amygdala.
AB  - Male Wistar rats were exposed to one-trial step-down inhibitory avoidance
      training using a 0.5 mA footshock. Through bilaterally implanted indwelling
      cannulae, they received bilateral 0.5 microl infusions of saline, oxotremorine
      (0.06 or 0.3 microg) or scopolamine (0.25 or 2.0 microg) into the basolateral
      complex of the amygdaloid nucleus (BLA). Infusions were either 10 min before
      training (experiment 1) or 4 min after training (experiment 2). In experiment 1,
      the animals were tested three times: first for working memory (WM) 2 s after
      training, then for short-term memory (STM) 1.5 h later, and finally for long-term
      memory (LTM) 24 h later. Oxotremorine enhanced and scopolamine depressed WM and
      LTM while leaving STM unaffected. In experiment 2, the treatments were given
      after WM was presumably over. Again, oxotremorine again enhanced and scopolamine
      depressed LTM, and neither had any effect on STM. The results fit with the
      suggestion by Beninger and his co-workers that cholinergic synapses in the BLA
      regulate WM, generalize that finding to a different task, and show that this
      mechanism uses muscarinic receptors. In addition, they indicate that the well
      known effects of intra-amygdala oxotremorine and scopolamine on LTM are
      independent of those that the drugs have on WM.

PMID- 11981230
TI  - Medical treatment of patients with infantile spasms.
AB  - Infantile spasms are the main feature in West syndrome, an age-related epilepsy
      syndrome that affects 1 in every 2,000-4,000 infants. The authors provide a
      comprehensive review of the literature about infantile spasms and their therapy.
      In the United States, the drug of choice for infantile spasms, at least the
      cryptogenic cases, has been adrenocorticotropic hormone (ACTH). It is generally
      considered to be more effective than corticosteroids. Adrenocorticotropic hormone
      appears to alter long-term prognosis of cryptogenic infantile spasms, and helps
      in some cases of symptomatic infantile spasm. Vigabatrin has been considered the
      drug of choice for infantile spasms secondary to tuberous sclerosis, and
      possibly, according to many neurologists, for all cases of infantile spasm.
      Recent concerns regarding retinopathy associated with vigabatrin therapy are,
      however, limiting the use of this drug. Valproic acid benefits 40%-70% of
      patients who failed a trial of ACTH. Nitrazepam is as effective as ACTH in
      acutely controlling infantile spasms; however, its long-term effects on prognosis
      have not been studied. Pyridoxine, lamotrigine, topiramate, zonisamide, ketogenic
      diet, immunoglobulin therapy, felbamate, and thyrotropin-releasing hormone have
      all been used for the treatment of infantile spasms, but are usually reserved for
      cases refractory to vigabatrin and/or ACTH.

PMID- 11981231
TI  - Treatment of patients with tardive dystonia with olanzapine.
AB  - Tardive dystonia represents a complication of long-term use of neuroleptics and
      its treatment is often unsatisfactory. Atypical neuroleptics appear to improve
      tardive dystonia, and cases of tardive dystonia successfully managed with
      clozapine have been reported. The aim of this open-label video-blinded study was
      to evaluate the antidystonic efficacy of olanzapine, a new atypical neuroleptic
      with a low risk of agranulocytosis, in a group of four patients (one man and
      three women) with tardive cervical dystonia. They developed severe dystonia after
      several years of neuroleptic treatment. Extensive laboratory evaluations, as well
      as neurophysiologic and neuroradiologic investigations, were negative. Olanzapine
      was started at a dose of 5 mg/d and increased up to 7.5 mg/d. All patients were
      evaluated at baseline and after 2, 4, 8, and 12 weeks of treatment, using the
      Toronto Western Spasmodic Torticollis Rating Scale, and videotaped. At the end of
      the trial, the videotapes were reviewed and scored by a blind observer. A self
      rating visual analog scale completed the disability evaluation.A moderate to
      marked improvement in dystonia was observed in all patients, and significant
      differences were observed in Toronto Western Spasmodic Torticollis Rating Scale
      scores and videotape ratings after 8 and 12 weeks of treatment compared with the
      basal values (p < 0.05). The average percentage of improvement in Toronto Western
      Spasmodic Torticollis Rating Scale score and visual analog scale was 26.4% and
      42.6%, respectively. No serious side effects were reported at the maximum dosage
      reached (7.5 mg/d). This study warrants a larger controlled study to conclusively
      demonstrate the efficacy of olanzapine in tardive dystonia.

PMID- 11981232
TI  - Morphometric evaluation of the neuroprotective effect of deprenyl on postaxotomic
      motor neuron losses.
AB  - Newborn rats were used to evaluate the neuroprotective effect of deprenyl on
      spinal motor neurons. The left sides were axotomized at age day 5 and the right
      sides were kept as a control. One hour after surgery, the operated animals
      received a daily dose of deprenyl intraperitoneally for 21 days. Each group
      received 0.25, 10, 30, 45, 60, or 75 mg/kg. The control side received the vehicle
      only. The number of motor neurons in the L4 through L6 spinal segments in all
      groups was counted, and the results were tested for normality using the
      Kolmogorov-Smirnov test. The number of the motor neurons at the axotomized
      treated sides were compared with those of the intact treated sides using analysis
      of variance. Significant differences (p < 0.05) were found in all groups except
      for the highest dose (75 mg/kg). The results in the untreated control showed a
      significant reduction in the percentage of motor neurons in the axotomized
      untreated group (-25.6%). The percentages of neuronal response and the
      percentages of maximal response were calculated, and the results show a sustained
      increase in percentage of neuronal response, with the highest response at a dose
      of 45 mg/kg followed by a decline. The results of the regression analysis show
      that there were two phases in the spinal motor neuron response: an initial
      neuroprotective phase followed by a neurotoxic declining phase. This study
      confirms the neuroprotectivity of motor neurons by deprenyl.

PMID- 11981233
TI  - Body weight influences pharmacokinetics of levodopa in Parkinson's disease.
AB  - Changes in body weight may induce substantial variations in peripheral
      pharmacokinetics of drugs, but the relation between body weight and levodopa (LD)
      pharmacokinetics has never been investigated in Parkinson's disease. To address
      this issue, we conducted a pharmacokinetic study with 164 patients with sporadic
      Parkinson's disease. Patients underwent an oral acute LD test with 250 mg of LD,
      and pharmacokinetic variables were assessed at baseline and at 30, 60, 120, and
      240 minutes after LD administration. Plasmatic-LD areas under the curve and body
      weight were significantly and inversely correlated as well as the elimination of
      the half-life of LD and body weight. In our sample, women were significantly
      lighter and had a significantly greater area under the curve than men. Moreover,
      a greater percentage of women showed LD peak-dose dyskinesias compared with men.
      Our findings suggest that lighter patients with Parkinson's disease probably
      receive a greater cumulative dosage of LD per kilogram of body weight during long
      term treatment, because in clinical practice, LD is administered without any
      adjustment of the dose to body weight. This could explain gender differences for
      the development of LD-induced peak-dose dyskinesias observed during the course of
      the disease.

PMID- 11981234
TI  - Comparison of the Unified Parkinson's Disease Rating Scale and the Short
      Parkinson's Evaluation Scale in patients with Parkinson's disease after levodopa
      loading.
AB  - The Short Parkinson's Evaluation Scale has been compiled and validated previously
      (Clinical Neuropharmacology, 1997). In the present study, we have assessed and
      compared the motor scoring of the Unified Parkinson's Disease Rating Scale and
      the Short Parkinson's Evaluation Scale in 23 patients (mean age, 61.8 years) with
      Parkinson's disease. Patients were 12 hours off medication at the beginning of
      the series. They were then given levodopa, 125 mg and 250 mg, on different days
      and were evaluated each 30 minutes for 2 hours. In addition, patients' motor
      skills (finger tapping and walking velocity) were measured at each time. Analysis
      of variance with repeated measures was applied. The results presented show that
      both scales have the same ability to measure levodopa-dose effect within time. In
      addition, Spearman's correlation coefficients showed a negative correlation
      between finger tapping and upper-limb impairment and a positive correlation
      between walking velocity and lower-limb impairment in both scales. In summary,
      the present results suggest that Short Parkinson's Evaluation Scale is a useful
      tool in assessing the effect of medication, having the advantage of being easier
      and quicker.

PMID- 11981235
TI  - Levodopa pharmacokinetics and motor performance during activities of daily living
      in patients with Parkinson's disease on individual drug combinations.
AB  - Pharmacokinetics and pharmacodynamics of levodopa were evaluated at a high
      resolution level in a heterogeneous group of 10 patients with idiopathic
      Parkinson's disease during their normal daily activity. A physician and a nurse
      spent 10 hours with each patient from the first morning dose of levodopa during
      daily activities at home and at work. Plasma samples were obtained every 20
      minutes for analysis of levodopa and 3-O-methyldopa by high-performance liquid
      chromatography. To assess clinical response, mobility was rated on every test
      occasion by patients and by investigators. Food and fluid intake and physical
      activity were also monitored. There was a large intra- and interindividual
      variability in the pharmacokinetics of levodopa regardless of the different drug
      combinations used. Mean plasma levodopa concentration ranged between 0.45 to 7.07
      microg/mL and peak concentrations between 0.95 to 13.75 microg/mL. In 44 of 58
      dosing events, an oral dose of levodopa was related to a peak in plasma
      concentration. Assessment of the clinical effects was more sensitive when given
      by patients than when given by the investigators. The fluctuations of the
      levodopa concentration in plasma had a clear effect on the clinical parameters
      assessed, even during early disease stages. Variation in levodopa concentration
      is the determining factor for motor fluctuations also in patients on clinically
      optimized combinations with dopamine agonists and enzyme inhibitors.

PMID- 11981236
TI  - Carbamazepine-risperidone interactions in patients with epilepsy.
AB  - Because concomitant administration of psychoactive and antiepileptic drugs is
      increasing progressively in neurologic and psychiatric practice, the aim of the
      current study was to evaluate the pharmacokinetic interactions between
      risperidone (RISP) and carbamazepine (CBZ) plasma concentrations in a group of
      patients with epilepsy with behavioral disturbances. The authors assessed eight
      patients on CBZ monotherapy (CBZ extended-release capsules) at a mean dosage of
      625 +/- 253 mg/day (range, 400-1,200 mg/day) for at least 1 year. RISP (1 mg in
      one daily dose) was added to CBZ therapy for the occurrence of behavior
      disturbances. CBZ blood levels were assessed before (T0), 24 hours after (T1),
      and 2 weeks after (T2) RISP administration. Steady-state plasma concentrations of
      CBZ increased from 6.67 +/- 0.41 microg/mL at baseline to 7.37 +/- 0.59 microg/mL
      (p < 0.01) at T1, to 7.95 +/- 0.47 microg/mL (p < 0.0001) at T2. The
      pharmacokinetic data suggest either a possible role of RISP in inhibiting the
      cytochrome P450 microsomal enzyme system (CYP)-3A4 pathway or a potential role of
      CYP2D6 in CBZ metabolism.

PMID- 11981237
TI  - Effects of subanesthetic doses of ketamine on sensorimotor information processing
      in healthy subjects.
AB  - Ketamine, an antagonist N-Methyl-D-Aspartate receptor, induces a broad range of
      anomalies in healthy subjects similar to those observed in psychosis. Previous
      studies have shown that information sensorimotor processing was impaired in
      patients with schizophrenia. The aim of the study was to assess the effects of
      subanesthetic doses of ketamine on behavior symptoms and information processing
      in healthy volunteers. A double-blind, crossover, placebo-controlled study was
      performed with eight subjects. Brief Psychiatric Rating Scale, Scale for the
      Assessment of Negative Symptoms, and Scale for the Assessment of Positive
      Symptoms assessed behavior changes. Information processing was assessed using a
      choice reaction time. Three experimental factors (stimulus intensity, stimulus
      response compatibility, and foreperiod duration) chosen to affect a different
      stage of information processing were manipulated. Our study has demonstrated that
      administration of ketamine produced significant effects on Brief Psychiatric
      Rating Scale, Scale for the Assessment of Negative Symptoms, and Scale for the
      Assessment of Positive Symptoms scores. Results on choice reaction time
      demonstrated a significant longer reaction time under ketamine. Effects of
      stimulus intensity and compatibility stimulus response were similar under
      ketamine and under placebo. Moreover, there was a specific interaction between
      ketamine and foreperiod. This interaction indicated that foreperiod's effect was
      more prolonged under ketamine (29 ms) than under placebo (17 ms). These results
      showed that the clinical effects of ketamine were associated with schizophrenic
      like impairments on choice reaction time in healthy subjects.

PMID- 11981238
TI  - Successful use of donepezil for the treatment of psychotic symptoms in patients
      with Parkinson's disease.
AB  - The risk of psychosis among patients with Parkinson's disease (PD) is high, and
      the management of these patients remains a substantial problem for physicians.
      Atypical antipsychotics, despite their advantages over conventional
      antipsychotics, can cause different side effects and deterioration of PD. Several
      reports have suggested that donepezil can be helpful in the treatment of
      psychotic conditions in patients with dementia with Lewy bodies and Alzheimer's
      disease. This report presents the results of preliminary study of six patients
      (four women, two men; age range, 60-75 years) with PD (range of duration, 3-7
      years) and dementia complicated by psychosis. All patients were treated with
      antiparkinsonian therapy, and donepezil was added to their regular treatment. The
      severity of the psychotic symptoms was assessed using the Scale for the
      Assessment of Positive Symptoms, and extrapyramidal symptoms were assessed using
      the Simpson-Angus Scale. With the addition of donepezil (as much as 10 mg/day) to
      their constant antiparkinsonian treatment, five patients had clinically
      significant (more than 53%) improvement on the assessment scale, and one patient
      had minimal (24%) improvement after 6 weeks of the treatment. None of the
      patients had side effects or deterioration of parkinsonian symptoms. The results
      suggest that donepezil may ameliorate psychotic symptoms in patients with PD, but
      this will need to be tested further in controlled, double-blind trials.

PMID- 11981239
TI  - Treatment of excessive daytime sleepiness in patients with Parkinson's disease
      with modafinil.
AB  - Excessive daytime sleepiness (EDS) may limit the symptomatic treatment of
      Parkinson's disease and can alter the patient's lifestyle significantly. Ten
      consecutive patients with Parkinson's disease on various dopaminergic drugs and
      EDS were recruited to a 4-week open-label trial of modafinil. Patients were
      evaluated using the Epworth Sleepiness Scale and Unified Parkinson's Disease
      Rating Scale part III. All but three patients, with previous history of
      intolerability of a dopamine agonist caused by EDS, remained on their baseline
      medications. Modafinil was titrated as needed to a maximum of 400 mg/day. The
      mean Epworth Sleepiness Scale score at baseline of patients completing the study
      (n = 9) was 14.22 (+/- 3.03). After completing the study on an average dose of
      172 mg/day, the Epworth Sleepiness Scale score was 6.0 (+/- 4.87). Unified
      Parkinson's Disease Rating Scale scores were not affected by this medication.
      Side effects encountered were headache, generalized paresthesias, and
      hallucinations (n = 1 each, the patient developing hallucinations dropped out of
      the trial before completing 4 weeks of the study drug). The three patients who
      did not tolerate any increments of dopamine agonist before modafinil were able to
      tolerate further upward titration of the dopamine agonist. Modafinil may be
      effective in reducing EDS in patients with Parkinson's disease treated with
      dopaminergic drugs. It does not seem to worsen parkinsonian symptoms and may
      allow further increase in dopaminergic therapy in patients previously unable to
      tolerate this because of EDS.

PMID- 11981240
TI  - Amantadine sulfate infusion effect on N30 somatosensory evoked potentials in
      Parkinson's disease.
AB  - The purpose of this study was to evaluate the effect of amantadine sulfate
      infusion on the N30 component of the median nerve short-latency somatosensory
      evoked potentials (SSEPs) in patients with Parkinson's disease (PD). Twenty
      patients with advanced PD and severe motor fluctuations received a 6-day course
      of amantadine sulfate infusion (400 mg/day) plus their usual levodopa medication.
      Patients were assessed clinically by means of the Unified Parkinson's Disease
      Rating Scale (UPDRS-III and -IV). SSEPs to median nerve stimulation were recorded
      from the parietal and frontal regions before and after the 6-day course of
      amantadine infusion. Mean UPDRS motor score during the ON and OFF phase improved
      after amantadine infusion, as did motor fluctuations. SSEP changes resulting from
      amantadine sulfate treatment were observed in the P20-N30 amplitude as follows:
      Mean P20-N30 amplitudes before and after treatment were 2.15 +/- 1.11 microV and
      3.06 +/- 1.19 microV respectively (p = 0.000), whereas mean N30-P40 amplitude
      increased from 2.7 +/- 1.6 microV to 3.9 +/- 1.3 microV after treatment (p =
      0.000). Our results indicate that coincident to its clinical impact, amantadine
      infusion in patients with PD affects electrophysiologic parameters as well.

PMID- 11981241
TI  - Motor response to apomorphine in patients with Parkinson's disease with long
      duration response to levodopa.
AB  - The authors studied the motor response to apomorphine before and 1 year after
      levodopa therapy in 12 patients with Parkinson's disease. At the 1-year
      evaluation, the basal tapping score, recorded after a 12-hour levodopa
      withdrawal, was higher compared with the test performed while patients were de
      novo, indicating the presence of a long-duration response to levodopa. The
      amplitude (net increase) of the motor response to apomorphine was similar before
      and during levodopa therapy. However, because of the better baseline, the maximal
      tapping score was higher during levodopa therapy. The duration and the latency of
      the motor response to apomorphine did not change. The presence of a short
      duration response to apomorphine, in the presence of a long-duration response to
      levodopa, may imply that either different compartment (i.e., postsynaptic versus
      presynaptic) or transduction pathways are involved in such responses.

PMID- 11981242
TI  - Centrally acting antiemetics mitigate nausea and vomiting in patients with
      Alzheimer's disease who receive rivastigmine.

PMID- 11981244
TI  - Anything but a biopsy: noninvasive monitoring for cardiac allograft rejection.
AB  - Endomyocardial biopsy has stood the test of time as a surveillance technique;
      however, the expense, resources required, invasive nature, and low but definite
      risks have motivated investigators to pursue less invasive techniques. The search
      for noninvasive surveillance techniques for cardiac rejection have centered on
      measurements of cardiac function, intragraft electrical events, peripheral
      proteomic markers of graft micronecrosis, immune activation, and nonimmune
      accompaniments of rejection. Although several investigations allude to a
      reasonable negative predictive value of such monitoring, the specificity of these
      techniques remains poor. Until well-constructed studies not only define the
      predictive values of noninvasive techniques but also appropriately evaluate the
      clinical safety of any such approach, invasive endomyocardial biopsy will remain
      the gold standard.

PMID- 11981245
TI  - Selecting patients for heart transplantation: which patients are too well for
      transplant?
AB  - In the context of contemporary medical and surgical therapy, the revolutionary
      procedure of cardiac transplantation should be redefined in its relative role.
      Based on the assumption that its goal is to prolong life while improving its
      quality, and in the absence of randomized clinical trial data testing its
      benefit, data from early breakthrough studies, more recent observational cohort
      studies, and studies testing other therapies in advanced heart failure must be
      analyzed to characterize clinical profiles of patients who should be considered
      too well for cardiac transplantation at specific stages of their disease
      processes. These profiles likely include advanced heart failure with (1) low risk
      according to the Heart Failure Survival Score, (2) peak oxygen consumption
      greater than 14 to 18 mL/kg/min without other indications, (3) left ventricular
      ejection fraction less than 20% alone, (4) history of New York Heart Association
      class III to IV symptoms alone, (5) history of ventricular arrhythmias alone, (6)
      no previous attempt at comprehensive neurohormonal blockade, and (7) no
      structured cardiac transplantation evaluation in a designated cardiac
      transplantation center. The evaluation may identify the potential transplant
      candidate, who could be placed on a national potential transplant candidate list,
      combining the psychologic benefit of acceptance by the program with an ongoing
      openness to the diversity of advanced heart failure treatment modalities.

PMID- 11981246
TI  - Heterotopic abdominal heart transplantation: a pilot study.
AB  - The increasingly severe shortage of donor hearts has prompted a liberalization of
      what is considered an acceptable donor heart. The use of marginally acceptable
      organs has increased in recent years. Although these marginal donors have proved
      effective, there still remains a tremendous shortage of donors to treat the large
      number of patients who are candidates for cardiac transplantation. Further use of
      marginal donors is limited by the requirement to assume immediate and full
      support of the circulation. New strategies are required to increase donor organ
      use even further. The authors developed a model of heterotopic abdominal heart
      transplant (HAHT) to investigate the possibility of using marginal donor hearts
      to expand the donor pool for cardiac transplantation. The authors' goal was to
      show that HAHT was technically feasible and could potentially function as
      auxiliary circulatory support in the setting of low cardiac output. The
      hemodynamic and metabolic consequences of a HAHT were investigated in a pilot
      study that provides proof of concept and lays the groundwork for future
      investigations.

PMID- 11981247
TI  - Children are not small adults: some differences between pediatric and adult
      cardiac transplantation.
AB  - Cardiac transplantation is a viable therapy for end-stage heart disease in both
      adults and children. Overall posttransplant survival in the pediatric age group
      (birth up to 18 years of age) is excellent (greater than 65% at 5 years for all
      age groups), comparable with the overall survival in the adult transplant
      recipients. Important differences exist regarding indications, evaluation,
      surgical technique, and posttransplant management. Indications for transplant in
      pediatric patients include metabolic and genetic forms of cardiomyopathy and
      structural congenital heart disease. Evaluation should include a metabolic
      workup, because potential etiologic factors include mitochondrial disorders, and
      genetic studies if indicated by phenotypic appearance or family pedigree.
      Children referred for transplantation with congenital heart disease have often
      had multiple attempts at palliative surgery, which increase peritransplant
      surgical risks. Key pediatric issues after transplantation include psychosocial
      support for the patient and family with regard to school, growth, development,
      and future expectations.

PMID- 11981248
TI  - Prevention of osteoporosis in cardiac transplant recipients.
AB  - Osteoporosis is a leading cause of pretransplant and posttransplant morbidity.
      The need for early detection by measuring bone mineral density, even before
      transplant, must be emphasized. Preventive measures are not comparable. The use
      of calcium and vitamin D supplements, although recommended, is inadequate for the
      prevention of bone loss and complications such as vertebral fractures.
      Bisphosphonates have been shown to attenuate the bone loss and reduce fractures
      associated with steroid-induced osteoporosis. Small studies in transplant
      recipients suggest similar results. Other preventive measures such as hormone
      replacement therapy are also helpful. There are limited data on the
      administration of nasal calcitonin in transplant recipients.

PMID- 11981249
TI  - Current practices: immunosuppression induction, maintenance, and rejection
      regimens in contemporary post-heart transplant patient treatment.
AB  - Cardiac transplantation is the definitive treatment for eligible patients with
      end-stage cardiomyopathy. Survival rates have improved dramatically during the
      last 10 years, especially since the advent of cyclosporine-A. Cardiac allograft
      rejection, previously considered a major cause of early mortality after
      transplantation, is no longer the limiting factor for early survival, with the
      use of newer and more specific immunosuppression regimens. Very few randomized,
      prospective trials, including comparisons between immunosuppression regimens,
      have been conducted in this area. Therefore, practices vary with physician and
      institutional experience. Most centers use a multipronged approach to
      immunosuppression, targeting multiple sites in the immune cascade that lead to
      allograft rejection. Multiple new agents in development are reviewed. Drugs such
      as sirolimus and its derivative, everolimus, act on specific intracellular
      receptors within lymphocytes, whereas other medications such as Daclizumab (Roche
      Laboratories, Nutley, NJ) block the interleukin-2 receptor on the surface of
      activated T cells. The immune response to foreign antigens is complex, with
      multiple redundant levels. Immunosuppression regimens continue to seek a fine
      balance between overimmunosuppression and insufficient protection, which may lead
      to allograft rejection or loss.

PMID- 11981251
TI  - Update on indications for surgery in aortic insufficiency.
AB  - Aortic insufficiency is a valvular disease characterized by left ventricular
      volume overload. This article presents a logical approach for following up
      patients with aortic insufficiency and helps to determine the optimal timing for
      valve replacement. The various valve replacement techniques are discussed, and
      the specific benefits or risks associated with these procedures are described.

PMID- 11981252
TI  - Mitral valve repair and the anterior leaflet.
AB  - Mitral valve repair with annuloplasty has become a widely accepted technique for
      correction of posterior leaflet mitral valve pathology. Advantages over mitral
      valve replacement include improved hemodynamic performance and improved
      ventricular function. Although repairs of the anterior leaflet met with less
      success initially, recent reports have emphasized the safety and effectiveness of
      chordal shortening, chordal transposition, and chordal replacement in treating
      disease of the anterior leaflet. Isolated annuloplasty and creation of double
      orifice mitral valves show promise for the treatment of mitral insufficiency in
      conjunction with heart failure and with other complex surgical procedures.

PMID- 11981253
TI  - The Carpentier-Edwards stented supra-annular pericardial aortic valve prosthesis:
      clinical durability and hemodynamic performance.
AB  - There are encouraging reports of satisfactory long-term experiences with second
      generation stent-mounted glutaraldehyde-fixed pericardial aortic valve
      prostheses. Durability has improved, but the issue has not been completely
      resolved. There is disagreement whether the small sizes of these prostheses are
      associated with inferior outcomes. Large-scale, long-term multivariable analyses
      of actual clinical results are needed to complement actuarial calculations of
      important end points from multiple small series to improve the ability to match
      individual patients with prostheses that suit their needs and preferences.

PMID- 11981254
TI  - Trauma to cardiac valves.
AB  - Cardiorrhaphy is a relatively common procedure performed in a trauma center.
      However, there is a subgroup of patients with more complicated cardiac injuries
      such as coronary artery injuries, septal defects, and valvular injuries. Cardiac
      valvular injuries are often diagnosed subacutely when a new murmur is heard.
      Transesophageal echocardiography has been increasingly performed to diagnosis
      these injuries and may be helpful intraoperatively. Cardiac catheterization may
      be indicated in selected patients. Techniques to address these injuries may
      involve repair or prosthetic replacement. A high index of suspicion is needed to
      diagnose these relatively rare injuries.

PMID- 11981255
TI  - Does non-malignant hypertension cause renal insufficiency? Evidence-based
      perspective.
AB  - While it is clear that malignant hypertension damages the kidneys, the question
      of whether non-malignant hypertension actually causes renal insufficiency remains
      controversial. A recent meta-analysis of 10 randomized controlled trials of
      antihypertensive drug therapy showed that patients randomized to antihypertensive
      therapy (or more-intensive therapy) did not show a significant reduction in their
      risk of developing renal dysfunction (relative risk, 0.97; 95% confidence
      interval, 0.78-1.21; P=0.77). A review of the totality of the evidence shows that
      there is relatively weak support for the thesis that non-malignant hypertension
      itself is an important de-novo cause (initiator) of renal insufficiency (as
      opposed to being a promoter of existing renal disease, which is a well
      established fact). Failure to evaluate the possibility that pre-existing renal
      disease could explain any observed association between elevated blood pressure
      and subsequent loss of renal function is an important limitation of published
      studies.

PMID- 11981256
TI  - Immunopathogenesis of lupus and lupus nephritis: recent insights.
AB  - Systemic lupus erythematosus is a multisystemic autoimmune disease. The
      immunopathogenesis is characterized by the loss of tolerance to self. While many
      abnormalities in the immune system have been detected, genetic factors play a
      central role in the pathogenesis. The event proximate to target organ involvement
      appears to be autoantigen-driven, T cell-mediated, B cell activation. High levels
      of autoantibodies are produced. However, not all autoantibodies are pathogenic to
      the kidney (i.e. 'nephritogenic'). These nephritogenic autoantibodies appear to
      share specific physiochemical features that correlate well with patterns of renal
      injury. While DNA was initially regarded as the inciting autoantigen, this view
      does not appear to be supported by the prevailing evidence. Nucleosomes, which
      are structures comprising histones and DNA, have emerged as the more likely
      candidate autoantigen. Autoantibodies directed against nucleosomes that cross
      react with nucleosomal epitopes have been identified. Furthermore, evidence
      suggests that immunoglobulin-nucleosomal complexes may be important in target
      organ immune deposition. In-vivo generation of nucleosomes requires apoptosis; in
      fact, there are several examples of aberrant apoptotic processes that present
      with autoimmunity. Aberrant apoptosis may also be critical in lupus
      immunopathogenesis. Indeed, studies on Fas/FasL and Bcl-2 in animal models and in
      humans have underscored the importance of apoptosis as an etiological factor in
      lupus. Cytokines, hormonal, infectious and environmental factors have also been
      found to be important in the pathogenesis of systemic lupus erythematosus.
      Overall, much progress has been made in elucidating the etiological agents and
      pathogenic mechanisms by which lupus develops. However, there is still some way
      to go before arriving at a unifying hypothesis. The reward for a better
      understanding of lupus immunopathogenesis will be the development of more
      specific targets for treatment, and the introduction of better and safer
      treatment modalities.

PMID- 11981257
TI  - Immunology of anti-glomerular basement membrane disease.
AB  - Anti-glomerular basement membrane disease is a form of autoimmune
      glomerulonephritis often accompanied by lung haemorrhage. It is characterized by
      circulating and deposited antibodies that bind basement membrane components in
      the glomerulus and lung alveolus. Since early descriptions of the deposition of
      immunoglobulin on the glomerular basement membrane, work has focused on the
      binding properties of the autoantibodies, and this has led to the identification
      of the autoantigen as the non-collagenous region of the alpha 3 chain of type IV
      collagen. Despite being thought of as a prototypic antibody mediated autoimmune
      disease, it is becoming apparent that both humoral and cellular immune mechanisms
      act in concert to initiate and perpetuate disease. Recent data have shed light on
      the molecular pathogenesis of anti-glomerular basement membrane disease and
      provided a more complete framework on which to build our understanding of
      autoimmune renal disease. This should lead to novel approaches to immunotherapy
      for patients with glomerulonephritis.

PMID- 11981258
TI  - Role of oxidized low-density lipoprotein in renal disease.
AB  - Accelerated atherosclerosis is often observed in patients with chronic renal
      failure. In the present review we summarize and discuss the recent literature on
      the pathogenic role of low-density lipoproteins modified by oxidative processes
      in atherosclerosis and the possible role in renal diseases. Pathogenetically, the
      oxidation of low-density lipoproteins is considered to be a key event in the
      development of atherosclerosis, in part by causing enhanced uptake of lipids by
      macrophages. In addition, oxidation of low-density lipoproteins exerts cytotoxic,
      proinflammatory and immunogenic properties, all of which could potentially
      contribute to the development and progression of atherosclerosis.

PMID- 11981259
TI  - Matrix metalloproteinases and angiogenesis.
AB  - Angiogenesis is a prominent feature of numerous diseases, including cancer and
      arthritis, and appears to play an important role in kidney disease and
      hypertension. The matrix metalloproteinases, especially matrix metalloproteinase
      2, play a vital role during angiogenesis by degrading the surrounding
      extracellular matrix and allowing endothelial cell invasion. Membrane type 1
      matrix metalloproteinase directly degrades matrix components as well as
      activating matrix metalloproteinase-2 on the cell surface. The integrin
      receptors, particularly alpha(v)beta(3), can recruit and possibly activate matrix
      metalloproteinases to localized microdomains on the cell membrane. This restricts
      matrix metalloproteinase activity to the pericellular region, preventing
      excessive matrix degradation which would otherwise impede endothelial invasion.
      Inhibitors of matrix metalloproteinase activity may actually promote cell
      invasion by preventing uncontrolled matrix degradation. In addition to degrading
      the matrix, matrix metalloproteinases produce protein fragments that impede their
      angiogenic action. These multiple regulatory pathways permit fine control over
      cell invasion during angiogenesis and provide new, precise strategies for
      targeting abnormal angiogenesis, through control of matrix metalloproteinase
      activity.

PMID- 11981260
TI  - Role of apoptosis in the pathogenesis of acute renal failure.
AB  - Renal tubular cells die by apoptosis as well as necrosis in experimental models
      of ischemic and toxic acute renal failure as well as in humans with acute tubular
      necrosis. It is not yet possible, however, to determine the relative contribution
      of these two forms of cell death to loss of renal tubular cells in acute tubular
      necrosis. The beneficial effect of administering growth factors to animals with
      acute tubular necrosis is probably related to the potent antiapoptotic (survival)
      effects of growth factors as well as to their proliferative effects. Rapamycin
      inhibits both of these effects of growth factors and delays the recovery of renal
      function after acute tubular necrosis by inhibiting renal tubular cell
      regeneration and by increasing renal tubular cell loss by apoptosis. The
      administration of caspase inhibitors ameliorates ischemia-reperfusion injury in
      multiple organs including the kidney. However, the extent to which this
      protective effect of caspase inhibition is caused by reduced intrarenal
      inflammation, or by amelioration of renal tubular cell loss due to apoptosis,
      remains uncertain. In addition to caspase inhibition, the apoptotic pathway
      offers many potential targets for therapeutic interventions to prevent renal
      tubular cell apoptosis.

PMID- 11981261
TI  - Molecular basis of polycystic kidney disease: PKD1, PKD2 and PKHD1.
AB  - Recent developments have helped elucidate the function of the autosomal dominant
      polycystic kidney disease proteins, polycystin-1 and polycystin-2, and have
      revealed the primary defect in autosomal recessive polycystic kidney disease, by
      positional cloning of the gene, PKHD1. Several studies demonstrating that
      polycystin-2 can act as a calcium-ion-permeable cation channel, and that
      polycystin-1 may be involved in regulating/localizing this channel, have provided
      compelling evidence of the function of these proteins. A role in regulating
      intracellular calcium levels seems likely, with the many cellular abnormalities
      associated with cystogenesis due to a disruption of calcium homeostasis. Improved
      mutation analysis in autosomal dominant polycystic kidney disease has led to the
      finding of genotype/phenotype correlations which could be related to possible
      cleavage of polycystin-1. A major recent breakthrough has revealed the primary
      defect in autosomal recessive polycystic kidney disease. Genetic analysis showed
      that the PCK rat model is orthologous to autosomal recessive polycystic kidney
      disease, and allowed the human gene, PKHD1, to be precisely localized and
      identified. PKHD1 is a large gene, encoding a protein, fibrocystin, of 4074 amino
      acids, which is predicted to have a large extracellular region, a single
      transmembrane domain and a short cytoplasmic tail. Fibrocystin may act as a
      receptor with critical roles in collecting-duct and biliary development.

PMID- 11981262
TI  - Recent advances in the immunology of chronic rejection.
AB  - Chronic allograft rejection is a slowly progressive, insidious process in which
      the host immune system continues to mount an immunological attack on a
      transplanted organ, ultimately resulting in the failure of the graft. To varying
      degrees, all solid organ grafts are at risk for chronic rejection and undergo a
      stereotypic process of injury and inflammation, eventually leading to parenchymal
      fibrosis. The clinical consequences of chronic rejection are particularly
      apparent in thoracic transplantation, where both patient and graft survival
      decline steadily over time and the opportunities for re-transplantation or long
      term extracorporeal support are limited. A variety of antigen-dependent and
      antigen-independent factors are known to modulate the propensity for an organ to
      undergo chronic rejection. Recent clinical and laboratory research has suggested
      that distinct immunologic mechanisms may underlie the process of chronic
      rejection. Ultimately, strategies to induce long-term tolerance to alloantigens
      will be necessary to prevent chronic rejection and to abrogate the deleterious
      sequelae of chronic immunosuppression.

PMID- 11981263
TI  - Hyperlipidemia in kidney disease: causes and consequences.
AB  - Dyslipidemias are common in patients with chronic kidney disease. The causes vary
      with the stage of kidney disease, the degree of proteinuria, and the modality of
      end-stage renal disease treatment. Dyslipidemias have been associated with kidney
      disease progression, and a number of small, randomized, controlled trials of
      lipid-lowering agents have been conducted. Unfortunately, the results of these
      trials, although encouraging, have been inconclusive because of the small numbers
      of patients enrolled. Dyslipidemias may also contribute to the high incidence of
      cardiovascular disease in patients with chronic kidney disease. This is most
      likely for patients with chronic renal insufficiency and for kidney transplant
      recipients. Less certain is the role of dyslipidemias in the pathogenesis of
      cardiovascular disease among dialysis patients.

PMID- 11981264
TI  - Obesity and renal disease.
AB  - Obesity, which has reached epidemic proportions in the United States and other
      western countries, may be complicated by hypertension, an increased incidence of
      renal cancer or proteinuria. Patients with obesity-associated proteinuria show
      focal glomerulosclerosis and glomerulomegaly on biopsy, usually have minimal
      clinical edema and relatively normal levels of serum albumin, cholesterol and
      blood pressure, and can progress to end-stage renal disease. Severe obesity may
      also be an additive risk factor in patients with preexisting nephropathy or
      reduced renal mass. The pathophysiology of obesity-associated proteinuria is
      unclear but may include hyperfiltration, increased renal venous pressure,
      glomerular hypertrophy, hyperlipidemia and increased synthesis of vasoactive and
      fibrogenic substances, including angiotensin II, insulin, leptin and transforming
      growth factor-beta1. These substances may individually or interactively affect
      glomerular hyperfiltration, mesangial cell hypertrophy and matrix production, and
      the production of collagen, fibronectin, transforming growth factor-beta and
      other fibrogenic mediators of change. Although angiotensin-converting enzyme
      inhibition has proven to have an impact, perhaps temporarily, on obesity
      associated proteinuria in humans, weight reduction early in the course of the
      disease would appear the most important therapeutic approach.

PMID- 11981265
TI  - Epidemiology of anemia associated with chronic renal insufficiency.
AB  - Several recently published reports have advanced our understanding of the
      epidemiology of anemia associated with chronic renal insufficiency. Anemia is
      commonly observed among subjects with chronic renal insufficiency. In comparison
      with subjects with preserved renal function, a significant decrease in hemoglobin
      could be detected in subjects with more modest degrees of renal insufficiency
      than was previously realized. Some of this undoubtedly reflects a decrease in
      renal production of erythropoietin, but these subjects may also suffer
      concomitant 'anemia of chronic disease'. Anemia is more likely not only among
      those with worse renal insufficiency, but also among black subjects, those with
      relative iron deficiency and those with lower serum albumin. Compared with those
      with preserved renal function, a significant decrease in hemoglobin could be
      detected in men at higher estimated creatinine clearance levels than in women;
      and at any given creatinine clearance, the decrease in hemoglobin is greater in
      men than in women. In the US, 800000 adults were estimated to suffer chronic
      renal insufficiency associated anemia, defined as hemoglobin level below 11 g/dl.
      As detailed in the present review, several methodological issues should be kept
      in mind when interpreting the literature. Further studies are needed to define
      the clinical implications of this common condition and to determine the most
      appropriate therapeutic response.

PMID- 11981266
TI  - Regional variation in end-stage renal disease.
AB  - Regional variations in end-stage renal disease have been found within a country,
      even within a race. Since diabetic nephropathy is the leading cause of end-stage
      renal disease in developed countries, first of all, regional differences in
      diabetic nephropathy must be considered. Although the incidence of end-stage
      renal disease due to diabetic nephropathy has been found to differ among
      different areas within a country, there are no data on regional variations in the
      incidence of type II diabetes or diabetic nephropathy without renal failure. Such
      regional variations could hardly be explained by local differences in gene pools
      alone, which suggests an important role of environmental factors. It is not clear
      at present how regional variations in the incidence of end-stage renal disease
      are generated. If we can identify the factors that contribute to the regional
      differences, we can take these into account in future treatment strategies for
      renal disease. Thus, much effort is required in further analysis of regional
      differences in end-stage renal disease dynamics.

PMID- 11981267
TI  - Birth weight and renal function.
AB  - Low birth weight due to premature birth or to intrauterine growth retardation
      adversely affects normal renal development. In the period immediately after
      birth, the short-term renal-related consequences of low birth weight are an
      increased risk of acute renal failure as well as transient imbalance of fluid and
      electrolyte homeostasis. Epidemiological studies show that low birth weight
      adults are at risk of developing chronic renal disease. There are thought to be
      several causes for this phenomenon. Adult low birth weight subjects have an
      increased incidence of hypertension and type 2 diabetes, both of which are well
      established risk factors for chronic renal injury. Moreover, interference with
      normal kidney development, as seen in low birth weight babies, results in a lower
      than normal number of nephrons, which might also play a role in the renal
      disturbances.

PMID- 11981269
TI  - Testicular cancer.
AB  - Testicular cancer remains a major success story in the realm of solid tumors.
      Although testicular cancer is highly treatable and curable, there are still many
      young men who succumb to the disease. Over the past year, important data
      regarding the diagnosis, treatment, and prognosis of testicular cancer have been
      reported. The significance of genetic and molecular alterations, such as i12p and
      epidermal growth factor receptor expression, remain at the forefront of research.
      However surgery and platinum-based chemotherapy are still the main treatment
      modalities. Attempts to limit chemotherapy and surgery while preserving cure
      rates are promising. The contribution of long-term platinum retention to the well
      documented risk of late toxicity is unknown but provides a specific avenue for
      research. New tumor markers, such as lactate dehydrogenase isoenzyme-1, may
      provide a greater risk stratification. Positron emission tomography imaging may
      reduce the need for surgical resection posttherapy and provide a more
      comprehensive means of observation.

PMID- 11981270
TI  - Bladder cancer.
AB  - Bladder cancer is a common and chemotherapy-responsive tumor, related to tobacco
      smoking, environmental arsenic exposure, industrial dye exposure, and parasitic
      schistosomiasis exposure. Both reduction of carcinogen exposure and
      chemoprevention, possibly with cyclooxygenase 2 inhibitors, should reduce the
      incidence. The search for the ideal screening and monitoring test continues with
      some promising new candidates, including survivin. Although 10-year survival can
      be achieved in 87% of early-stage patients with muscle-invasive disease rendered
      T(0) and 57% of those rendered T(1) at second look after transurethral resection
      bladder tumor, most still require radical cystectomy. Continued improvements in
      surgical techniques permit gains in quality of life after the procedure. Ten-year
      survival can still be achieved with cystectomy in the face of grossly positive
      lymph nodes in 32% of T(2) and 10% of T(3) patients. A recent meta-analysis
      indicates that preoperative irradiation is unlikely to be beneficial, but
      definitive chemoradiation can produce significant 5-year survival rates in
      nonoperative candidates and those desiring bladder preservation. The Intergroup
      now has preliminary data from a Southwest Oncology Group-based trial showing a
      significant benefit for neoadjuvant methotrexate, vinblastine, doxorubicin, and
      cisplatin. The regimen of gemcitabine and cisplatin is equally efficacious with
      less toxicity than methotrexate, vinblastine, doxorubicin, and cisplatin. It has
      been adopted as the standard arm in a phase III trial for advanced bladder
      cancer, comparing it with the triplet of gemcitabine, paclitaxel, and cisplatin.
      Other active agents in bladder cancer include ifosfamide, carboplatin, docetaxel,
      and vinorelbine, and various doublets of these agents are being tested in phase
      II trials, with promising results.

PMID- 11981271
TI  - Pediatric genitourinary tumors.
AB  - Each year advances are made in the clinical evaluation and treatment of
      genitourinary tumors in children. Understanding of cellular, molecular, and
      genetic processes in tumorigenesis is evolving rapidly. In addition, information
      is accumulating about the long-term outcome and complications associated with
      treatment modalities. This article reviews the 2001 literature on pediatric Wilms
      tumor, other renal tumors, rhabdomyosarcoma of the pelvis, paratesticular
      rhabdomyosarcoma, and testicular tumors. The emphasis in molecular biology is to
      identify molecular or genetic markers that predict outcome. The National Wilms'
      Tumor Study Group reported on the complications of surgery and the decreased
      complication rate when these procedures are performed by pediatric surgical
      specialists. Long-term complications of treatment are also discussed, including
      short stature and leukemia. The Intergroup Rhabdomyosarcoma Study Group reported
      on the results of treatment for nonmetastatic disease and the goals of the
      upcoming Study V, reduction of chemotherapy and radiotherapy. They also presented
      data from Study IV and discussed the findings on improved prognosis.

PMID- 11981272
TI  - Renal cell carcinoma.
AB  - Renal cell carcinoma continues to be a difficult malignancy to treat because of
      its ability to spread asymptomatically and its inherent resistance to
      conventional chemotherapy. However, molecular genetic studies bring new insights
      into the pathogenesis of this disorder and may provide new targets against which
      novel chemotherapeutic agents could be developed. Nephron-sparing surgery is also
      gaining wider acceptance as favorable long-term, cancer-free survival data emerge
      from clinical trials. For metastatic disease, cytokine therapy continues to be
      the mainstay of treatment despite marginal efficacy and a significant side-effect
      profile.

PMID- 11981273
TI  - Prostate cancer update.
AB  - Recent advances in prostate cancer have focused on treatment strategies in
      patients with biochemical relapse and novel methods of androgen deprivation
      therapy such as intermittent therapy, the role of bisphosphonates, and
      immunotherapeutic approaches. Continued investigation into the mechanism of
      androgen independence and effective treatments for hormone-refractory disease are
      described. This article reviews the major advances in prostate cancer published
      between November 1, 2000, and October 31, 2001.

PMID- 11981274
TI  - The potential of proton magnetic resonance spectroscopy ((1)H-MRS) in the
      diagnosis and management of patients with brain tumors.
AB  - Proton ((1)H) magnetic resonance spectroscopy (MRS) is a noninvasive method that
      can monitor the metabolic changes in most brain diseases. This technique is now
      available on current 1.5 Tesla magnetic resonance units and does not require
      sophisticated software or time-consuming post-processing techniques. Previous
      studies using single-voxel techniques showed the usefulness of MRS for the
      diagnosis of brain tumor despite some technical issues, including spatial
      resolution and volume coverage. Recent advances have been made through the use of
      multivoxel techniques and metabolite maps, which allow assessment of both the
      entire volume of the lesion and the surrounding normal-appearing brain tissue.
      Recent studies suggest the potential of this technique to guide biopsies, to
      define radiotherapy targets, and to monitor patients after treatment. Some
      persistent drawbacks, including measurement time and spectral resolution, will
      probably be overcome in the near future.

PMID- 11981275
TI  - Medical management of patients with brain tumors.
AB  - The most common medical problems in brain tumor patients involve the management
      of seizures, peritumoral edema, medication side effects, and venous
      thromboembolism. Despite the importance of these issues, there are very few
      studies specifically addressing them. Nonetheless, there has been some progress
      in recent years. There is increasing evidence that brain tumor patients who have
      not had a seizure do not benefit from prophylactic antiepileptic medications.
      Patients taking corticosteroids are at greater risk of Pneumocystis carinii
      pneumonia and may benefit from prophylactic therapy. There is also growing
      evidence suggesting that anticoagulation may be more effective than inferior vena
      cava filtration devices for treating venous thromboembolism in brain tumor
      patients and that the risk of hemorrhage with anticoagulation is relatively
      small.

PMID- 11981277
TI  - Genetic susceptibility--molecular epidemiology of head and neck cancer.
AB  - In parts of the developing world (South Central Asia in particular), squamous
      cell carcinoma of the head and neck (SCCHN) is one of the most common
      malignancies encountered. Although tobacco and alcohol are clearly defined as
      etiologic factors in these malignancies, clinical observations have suggested
      that inherited genetic factors put some individuals at increased risk for SCCHN.
      Emerging data (both phenotypic and genotypic) support this concept of genetic
      susceptibility to SCCHN and point to differences in DNA repair ability,
      carcinogen metabolism, and cell cycle control as the systems important to the
      risk of tobacco-induced malignancies. The ability to identify such high-risk
      individuals will have major influences on the practice of cancer prevention in
      the future.

PMID- 11981278
TI  - Chemoprevention of head and neck cancer: an update.
AB  - Squamous cell carcinoma of the head and neck is an important public health
      problem worldwide that is clearly associated with the widely accepted risk
      factors of tobacco smoking and alcohol use and is the end result of a multiyear,
      multipath disease process of progressive genetic and associated tissue damage.
      Chemoprevention, the use of drugs or other agents to inhibit, delay, or reverse
      this process, is recognized as a very promising and important area in head and
      neck cancer research. Chemoprevention research is based on the increasing body of
      knowledge of the biology underlying head and neck tumorigenesis and is expected
      to ultimately result in a decrease in the incidence of head and neck cancer.

PMID- 11981279
TI  - Update on chemoradiotherapy for head and neck cancer.
AB  - Locoregionally advanced head and neck cancer is associated with a poor prognosis
      despite treatment with surgery or radiation or both. In the past several years,
      chemotherapy has become an integral part of potentially curative therapy for head
      and neck cancer and has been increasingly used to achieve the goals of organ
      preservation and prolongation of survival. Since 1998, many randomized studies
      that compared concurrent chemoradiotherapy with radiotherapy alone have been
      published. These studies used different chemotherapy regimens, either single
      agent or combination, and various radiation fractionation schemes and almost
      uniformly supported the superiority of chemoradiotherapy over radiotherapy alone
      in terms of locoregional control as well as overall survival. Given the toxicity
      of concurrent chemoradiotherapy, careful selection of patients is critical. Many
      issues remain to be addressed in future trials, including the optimal
      chemotherapy regimen, the use of altered fractionation radiotherapy, and the role
      of induction chemotherapy.

PMID- 11981280
TI  - Reirradiation: a potentially curative approach to locally or regionally recurrent
      head and neck cancer.
AB  - The treatment options for patients with recurrent head and neck malignancies
      arising in a previously irradiated field are limited. Surgical salvage is
      feasible in a minority of patients. The majority are referred for palliative
      chemotherapy with no realistic chance for cure. Data are accumulating to support
      reirradiation as a potentially curative approach for patients with locally or
      regionally recurrent head and neck cancer. This article provides a rationale for
      management and reviews recent results of reirradiation.

PMID- 11981281
TI  - Novel therapeutics for head and neck cancer.
AB  - Head and neck squamous cell carcinoma is a clinically challenging disease that
      resulted in more than 500,000 cases worldwide in 2001. In the United States, head
      and neck squamous cell carcinoma has accounted for approximately 40,000 cases
      with 12,000 deaths reported in 2001, which makes it the fifth leading cause of
      cancer incidence and the sixth leading cause of cancer-related deaths. Patients
      with recurrent or metastatic disease have a median survival rate of approximately
      6 months; and there is little evidence from randomized trials that survival
      advantages have been achieved over the community standard of cisplatin and
      infusional 5-fluorouracil combination. Despite significant improvements in
      diagnosis, local management, and chemotherapy of head and neck cancer, there has
      been no significant increase in long-term survival rates over the past 30 years.
      As little progress has been made, new management approaches are required. Novel
      biologic agents have been developed to target multiple specific regions of the
      cancer cell. Epidermal growth factor receptor blockers have been investigated,
      such as anti epidermal growth factor receptor monoclonal antibodies, tyrosine
      kinase inhibitors, ligand conjugates, immunoconjugates, and antisense
      oligonucleotides. Farnesyl transferase inhibitors are a class of compounds that
      inhibit a critical enzymatic step in the constitutive expression of mutated ras
      genes, which are present in more than 27% of oral cancers. Strategies targeting
      the p53 gene and protein may halt or reverse the process of tumorigenesis and
      metastasis as p53 mutations occur in 45 to 70% of head and neck squamous cell
      carcinoma patients. Continued development of these novel agents may help improve
      the overall response and survival rate of patients with head and neck cancer.

PMID- 11981283
TI  - Uses and abuses of sodium bicarbonate in the neonatal intensive care unit.
AB  - Despite the lack of evidence for its effectiveness in the treatment of acid-base
      disturbances in critically ill patients of all ages, and despite several lines of
      evidence that indicate it might be dangerous, bicarbonate therapy is used
      routinely in many neonatal intensive care units. The justification for the
      persistent use of this controversial therapy comes from a variety of sources,
      many based more in philosophy than in science. Clinicians contemplating the use
      of bicarbonate therapy should consider what they expect the intervention to
      accomplish and what evidence exists that their therapeutic objective will be met.
      Without rigorous scientific support for this therapy, it should be considered of
      unproven value and, therefore, experimental.

PMID- 11981284
TI  - Prevention of nosocomial infections in the neonatal intensive care unit.
AB  - Nosocomial infections are responsible for significant morbidity and late
      mortality among neonatal intensive care unit patients. The number of neonatal
      patients at risk for acquiring nosocomial infections is increasing because of the
      improved survival of very low birthweight infants and their need for invasive
      monitoring and supportive care. Effective strategies to prevent nosocomial
      infection must include continuous monitoring and surveillance of infection rates
      and distribution of pathogens; strategic nursery design and staffing; emphasis on
      handwashing compliance; minimizing central venous catheter use and contamination,
      and prudent use of antimicrobial agents. Educational programs and feedback to
      nursery personnel improve compliance with infection control programs.

PMID- 11981285
TI  - Evidence-based neonatology: making a difference beyond discharge from the
      neonatal nursery.
AB  - The number of controlled clinical trials in neonatal medicine has increased
      steadily over recent years. However, most of these trials examine only short-term
      outcomes during the initial hospital stay. To determine whether a common neonatal
      intervention does more good than harm, it is important to study its long-term
      efficacy and safety. This review summarizes randomized trials of neonatal
      therapies published between October 2000 and September 2001. Only trials that
      examine outcomes beyond the initial hospital discharge were considered. Four
      beneficial interventions were identified: promotion of breast-feeding,
      comprehensive follow-up care for high-risk, very low birthweight infants,
      cryotherapy for threshold retinopathy of prematurity, and extracorporeal membrane
      oxygenation for mature infants with severe respiratory failure. Indomethacin
      prophylaxis in extremely low birthweight infants is of questionable use.
      Thyroxine supplementation for premature infants and head cooling for asphyxiated
      term infants require further study and should not be prescribed outside of
      rigorous clinical trials.

PMID- 11981286
TI  - Current opinion in pediatrics: ethics and law 2001.

PMID- 11981287
TI  - Renal aspects of the term and preterm infant: a selective update.
AB  - This review discusses new aspects of normal and abnormal renal development that
      expand insight into the adaptation of the neonatal kidneys to the stress of
      extrauterine life. Highlighted are some pitfalls in measuring glomerular
      filtration rate in the neonate mainly caused by postnatal fluctuations in serum
      creatinine levels. Serum creatinine levels are correlated with the authors'
      recent finding of tubular reabsorption of creatinine in the immature neonatal
      kidney. Renal maldevelopment in premature and small-for-date babies has been
      shown related to serious medical problems in adult life, including hypertension.
      This finding presents the pediatrician with a new role in the time-honored
      vocation of preventing disease. Mutations in several genes may be responsible for
      most cases of congenital or hereditary renal aberrations. Two renal disorders,
      congenital nephrotic syndrome and neonatal acute renal failure, and one form of
      treatment modality of newborn infants, renal replacement therapy, are discussed
      in detail. These conditions are rare in general pediatric practice, but they
      illustrate some of the new developments in the renal care of the newborn. A word
      of caution is offered about the use of nonsteroidal anti-inflammatory drugs
      during pregnancy and the newborn period. All nonsteroidal anti-inflammatory drugs
      administered indirectly to the unborn fetus and directly to the young newborn
      impair renal structure (fetus) and function (both fetus and newborn). The new
      data have been obtained with genetic and molecular biology techniques and with
      established methods of developmental renal physiology. A better understanding of
      the pathogenesis of neonatal renal disorders will result in new diagnostic
      procedures and improved preventive and therapeutic possibilities relevant to the
      neonate with a renal disorder.

PMID- 11981288
TI  - Acute renal failure.
AB  - Acute renal failure is characterized by an increase in the blood concentration of
      creatinine and nitrogenous waste products and by the inability of the kidney to
      appropriately regulate fluid and electrolyte homeostasis. There are many
      different causes of acute renal failure in children, including prerenal disease,
      intrinsic renal failure, which includes ischemic hypoxic insults, and obstructive
      uropathy. This review will focus on hypoxic/ischemic acute renal failure, the
      most common causes of hospital acquired acute renal failure in children. This
      review will briefly discuss the epidemiology and incidence of acute renal failure
      in pediatric patients and review new insights into the pathogenesis of acute
      renal failure. including hemodynamic alterations induced by alterations in nitric
      oxide and endothelin metabolism, the role of the inflammatory response, and
      alteration in polarity in the acute renal failure. The therapy of acute renal
      failure has changed substantially during the past few years. Controlled trials
      (in adults) to test the efficacy of "renal dose" dopamine have shown that it is
      ineffective, and hemofiltration has become increasingly popular as a choice of
      therapy for acute renal failure.

PMID- 11981289
TI  - Pediatric hypertension: recent literature.
AB  - This article reviews selected recent literature specifically concerning pediatric
      hypertension, much of which has focused on measurement and monitoring of blood
      pressure, as well as on evaluating antihypertensive medications. Normative data
      for blood pressure in children have been widely available for some time, based
      upon seated in-office measurements. In recent years, ambulatory blood pressure
      monitoring (ABPM), facilitated by user-friendly instrumentation, has become more
      commonplace, though norms are not based on large populations. However, ABPM has
      important uses in assessing blood pressure as well as in monitoring
      antihypertensive. This review discusses issues involved in determining blood
      pressure, as well as the utility of ABPM in several situations. Recent
      developments concerning pediatric antihypertensive therapy are considered, as
      well as new information relevant to the diagnosis, course and treatment of
      hypertension in children and adolescents.

PMID- 11981290
TI  - Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and
      management.
AB  - Dyslipidemia increases the risk of cardiovascular events among individuals with
      renal disease, and there is a growing body of evidence that it hastens the
      progression of renal disease itself. Children with nephrotic syndrome or renal
      transplants have easily recognized hyperlipidemia. Among those with chronic renal
      insufficiency or end-stage renal disease, detection of dyslipidemia requires more
      careful analysis and knowledge of normal pediatric ranges. Disordered lipoprotein
      metabolism results from complex interactions among many factors, including the
      primary disease process, use of medications such as corticosteroids, the presence
      of malnutrition or obesity, and diet. The systematic treatment of dyslipidemia in
      children with chronic renal disease is controversial because conclusive data
      regarding the risks and benefits are lacking. Hepatic 3-methylglutaryl coenzyme A
      reductase inhibitors (statins), fibrates, plant stanols, bile acid-binding
      resins, and dietary manipulation are options for individualized treatment.
      Prospective investigations are required to guide clinical management.

PMID- 11981291
TI  - Long-term care of pediatric renal transplant patients: from bench to bedside.
AB  - In this review, we discuss current and future issues in the management of
      pediatric renal transplant recipients, including the optimization of long-term
      graft function and the minimization of complications caused by immunosuppression.
      Long-term management involves not only the monitoring of graft function but also
      the identification of patients at risk for the development of complications. The
      identification of patients with immunoreactive or immunoregulatory responses can
      be performed molecular monitoring of the immune response. Also, the use of
      frequent surveillance kidney biopsies, surrogate markers of chronic rejection,
      and glomerular filtration rate will be a part of future management. Identifying
      high-risk patients enables the physician to optimize immunosuppression to limit
      acute rejection. Short-and long-term management of pediatric transplant patients
      also includes adequate monitoring of growth and the monitoring for post
      transplant lymphoproliferative disease. Ongoing clinical trials are underway that
      focus on these novel approaches in caring for pediatric transplant recipients.

PMID- 11981292
TI  - Use, abuse, toxicity, and monitoring of pediatric psychotropic drug therapy: new
      issues for the new millennium.

PMID- 11981293
TI  - Pharmacologic treatment of adolescent depression.
AB  - Depression is a disease entity that causes significant morbidity and mortality in
      the adolescent population. It is important for primary care providers to
      recognize the signs and symptoms associated with depression in adolescents. This
      article discusses the current literature addressing the pharmacologic treatment
      of adolescent depression. A brief review of diagnosing depression is included.
      Diagnosis of depression in the adolescent with normal and abnormal development is
      examined, along with risk factors associated with increased incidence of
      depression in this population. Past and present clinical trials of tricyclic,
      monoamine oxidase inhibitor, and selective serotonin reuptake inhibitor classes
      of antidepressants are reviewed. In addition, adverse effects and toxicity are
      briefly discussed. Currently, the selective serotonin reuptake inhibitors are the
      first-line pharmacologic intervention for adolescent depression, although only
      selected drugs have undergone controlled clinical trials in this age group. The
      high toxicity profile of other classes of antidepressants makes their choice less
      optimal. Newer antidepressants have also been studied recently in the adolescent
      population. Further pharmacotherapy research in this vulnerable cohort is needed.

PMID- 11981294
TI  - Abuse and toxicity of methylphenidate.
AB  - The therapeutic use of methylphenidate for the management of attention-deficit
      hyperactivity disorder in children is increasing. As therapeutic use increases,
      the risk increases of unintentional overdoses, medication errors, and intentional
      overdoses caused by abuse, misuse, or suicide gestures and attempts. Side effects
      during therapy, which include nervousness, headache, insomnia, anorexia, and
      tachycardia, increase linearly with dose. Clinical manifestations of overdoses
      include agitation, hallucinations, psychosis, lethargy, seizures, tachycardia,
      dysrhythmias, hypertension, and hyperthermia. Methylphenidate tablets can be
      abused orally, or they can be crushed and the powder injected or snorted. Despite
      its abuse potential, there is disagreement regarding the extent to which
      methylphenidate is being diverted from legitimate use to abuse in preteens and
      adolescents.

PMID- 11981295
TI  - Effects of psychotropic medications on the pediatric electrocardiogram and
      recommendations for monitoring.
AB  - Reports of sudden unexpected death in pediatric patients taking selected
      psychotropic drugs have raised the possibility of ventricular dysrhythmias as the
      cause of these deaths. The use of psychotropic drugs in the pediatric population
      has increased significantly in recent years with increasing reports of
      electrocardiogram abnormalities, particularly prolongation of the corrected QT
      interval. Many factors affect the susceptibility of the heart to conduction
      abnormalities and sudden ventricular dysrhythmias in pediatric patients taking
      psychotropic drugs. These complex relations include genetic predisposition,
      structural cardiac disease, drug-drug interactions, drug dosage, and drug
      metabolism and clearance. Many specific psychotropic drugs have been reported to
      prolong the QTc interval and increase the risk of ventricular dysrhythmias and
      sudden death. This article discusses the various factors that may influence the
      electrocardiogram in pediatric patients taking psychotropic drugs and
      recommendations for monitoring these patients.

PMID- 11981296
TI  - Persistent silent aspiration in a child with Trisomy 21.

PMID- 11981298
TI  - Attention-deficit/hyperactivity disorder: a therapeutic update.

PMID- 11981299
TI  - Sudden infant death syndrome.

PMID- 11981300
TI  - Child abuse and neglect.

PMID- 11981302
TI  - Modulating airway defenses against microbes.
AB  - Prevention and treatment of respiratory infections remain an important health
      care challenge as the US population ages, contains more susceptible or high-risk
      people, and encounters new pathogens or antibiotic resistant bacteria. Reasonably
      protective vaccines against very common microbes are available for childhood and
      adult immunization, but, generally, these are underutilized. A broader definition
      of higher risk individuals is evolving, which will include more for immunization.
      Different approaches to vaccine development through design of new component
      vaccines are necessary. This review has updated host defense mechanisms at three
      levels in the human respiratory tract: naso-oropharynx (upper airways),
      conducting airways, and alveolar space. Examples of representative pathogenic
      microbes have been inserted at the respective airway segment where they may
      colonize or create infection (influenza, measles virus, Porphyromonas gingivalis
      causing periodontitis, Bordetella pertussis, Chlamydia pneumoniae, Streptococcus
      pneumoniae, and Bacillus anthracis ). Hopefully, microbe-host interactions will
      suggest new approaches for preventing these kinds of infections.

PMID- 11981303
TI  - Infection and disease caused by environmental mycobacteria.
AB  - Many species of mycobacteria that normally live as environmental saprophytes, the
      environmental mycobacteria (EM), are opportunist causes of disease in humans and
      animals. Many, but not all, cases are associated with some form of immune
      deficiency. An increasing number of species and clinical presentations are being
      described, and advances are being made in the understanding of the underlying
      predisposing factors. In recent years, four aspects of EM disease have become
      particularly relevant to human health: (1) the high prevalence of EM disease in
      patients with AIDS; (2) the emergence of Buruli ulcer, an ulcerative skin disease
      caused by Mycobacterium ulcerans, as the third most prevalent mycobacterial
      disease; (3) the effect of infection by EM on the immune responses to BCG
      vaccination and on the course and outcome of tuberculosis and leprosy; (4) the
      controversy over the involvement of mycobacteria, notably M. avium subspecies
      paratuberculosis, in human inflammatory bowel disease. These aspects change the
      status of EM from mere curiosities to important direct, indirect, and putative
      causes of serious and increasingly common human disease.

PMID- 11981304
TI  - Advances in adult pulmonary tuberculosis.
AB  - The immune response is able to contain but not eliminate Mycobacterium
      tuberculosis. Antigens that are specific to M. tuberculosis can identify latent
      infection accurately even after BCG vaccination. Genes that are required for
      persistence of the organism have been identified and new drugs are being
      developed to disrupt their function. This offers the hope of shortened courses of
      therapy. New drugs are urgently needed for multidrug-resistant tuberculosis,
      particularly as some areas are reporting a high prevalence of fluoroquinolone
      resistance. The sputum smear is the standard rapid diagnostic test for pulmonary
      tuberculosis, but is frequently negative in HIV infection. The yield of smear can
      be increased by sputum induction and by concentration. Innovative methods of
      providing directly observed therapy have been devised. Preventive therapy is
      effective in HIV infection and probably improves survival. However, the duration
      of benefit of preventive therapy seems to be relatively short-lived. Effective
      long-term reduction of tuberculosis risk in HIV-infected patients can be achieved
      with highly active antiretroviral therapy.

PMID- 11981305
TI  - Childhood tuberculosis: out of control?
AB  - Because of the difficulty of confirming the diagnosis of childhood tuberculosis
      and because children do not make a significant contribution to the spread of
      tuberculosis, the burden of childhood tuberculosis in the world is uncertain.
      Several estimates make use of an arbitrary calculation assigning 10% of the
      tuberculosis burden to children. Available data linking the incidence of
      tuberculosis to the proportion of the tuberculosis caseload represented by
      children suggest an exponential rise in the proportion of the tuberculosis
      caseload caused by children as the tuberculosis incidence rises so that children
      may constitute nearly 40% of the caseload in certain high incidence communities.
      This review discusses the global burden of childhood tuberculosis and attempts to
      quantify this, the role of HIV/AIDS and tuberculosis in children, the problems
      this creates for diagnosis, and the occurrence of drug resistant tuberculosis in
      children. In the developing world, childhood tuberculosis is not under control,
      and, despite its importance as a child health problem, remains a neglected orphan
      disease.

PMID- 11981306
TI  - Tuberculosis vaccine development.
AB  - If the end of the 20th century saw the flowering of genomics, the beginning of
      the 21st century is witnessing an equally rapid blossoming of proteomics. These
      twin technologies have had a dramatic influence on the study of tuberculosis
      (TB), and nowhere more so than in the development of new TB vaccines. Only a few
      years ago, it was generally accepted that clinical trials of new TB vaccines
      would not take place for at least a decade. However, the first trials are now
      scheduled to start within months. Much TB vaccine research has thus shifted from
      developing new vaccines, to selecting the best vaccines for human use from the
      increasing number of effective new candidates becoming available. This selection
      is being eased by the improved animal models that have been developed over the
      past few years and by our increasing understanding of immunity to TB.

PMID- 11981307
TI  - Nosocomial and ventilator-associated pneumonias: developing country perspective.
AB  - Nosocomial pneumonias are recognized as an important cause of morbidity and
      mortality in industrialized nations. Emerging data show that they play a similar
      role in the developing world. A host of extrinsic and intrinsic factors
      predispose individuals to the development of pneumonias, and a modification of
      some of these factors provides a low cost solution to prevention of pneumonias.
      The ideal modality for microbiologic diagnosis of pneumonia remains to be
      determined. Recent data suggest that there is no difference in outcome when
      noninvasive techniques are compared with invasive techniques. Antimicrobial
      resistance is a rapidly increasing problem globally, and combating this with
      appropriate antibiotic policies, close surveillance, and physician education is
      essential.

PMID- 11981308
TI  - Invasive pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in
      certain immunocompromised patients. The most commonly affected patients are
      hematopoietic stem cell transplant recipients and patients with hematological
      malignancies undergoing intensive chemotherapy. The survival of patients with
      invasive pulmonary aspergillosis is very poor because of difficulties in early
      diagnosis and lack of effective treatment options. Research efforts are being
      made constantly to improve different diagnostic techniques. Early, repeated, high
      resolution computed tomography of the chest, and sequential nonculture-based
      monitoring of Aspergillus antigen and DNA can improve earlier diagnosis. New
      antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis
      continue to emerge, with better safety, efficacy, and pharmacologic profiles.

PMID- 11981309
TI  - Respiratory viral infections in adults.
AB  - Respiratory viral infections in adults cause significant morbidity and mortality,
      especially in high-risk patients. The impact of influenza virus, rhinoviruses,
      and respiratory syncytial virus in immunocompromised cancer patients and in
      asthma and chronic bronchitis patients has been documented in recent
      publications. Cytomegalovirus pneumonia continues to be a major cause of
      morbidity and mortality in transplant recipients. Newer rapid diagnostic tests
      and the use of polymerase chain reaction technology have provided better
      understanding of the causes and epidemiology of acute respiratory illness in
      adults. The approved neuraminidase inhibitors for influenza viruses and the
      nonapproved capsid inhibitors of rhinoviruses may be useful in treating high-risk
      individuals. The inactivated influenza vaccine has been shown to benefit healthy
      adults and to be safe in asthmatic adults and children.

PMID- 11981310
TI  - Influenza update: vaccine development and clinical trials.
AB  - Although influenza activity throughout the world has been relatively low during
      the past year, epidemics of influenza A, in particular, which are caused by new
      virus variants, continue to be a major public health problem. Widespread
      vaccination is the only rational measure that can be used for the prevention of
      illness in key risk groups. Although current inactivated split/subunit vaccines
      are reasonably effective, significant improvements have been shown to be possible
      in the boosting of responses by the use of particular adjuvants and/or the direct
      administration of vaccines to the respiratory tract. Live attenuated vaccines,
      also administered directly to the respiratory tract, have continued to be shown
      to be safe and effective, and, in the longer term, probably will have a major
      role in influenza prophylaxis, especially in children and young adults.

PMID- 11981311
TI  - Respiratory syncytial virus infection: clinical features, management, and
      prophylaxis.
AB  - Respiratory syncytial virus (RSV) infects almost all children by two years of
      age, resulting in a large number of hospital admissions in infants. Reactive
      airway disease is more common after RSV infection, even in previously healthy
      children. Management of the acute infection is supportive, but preliminary
      evidence suggests surfactant administration to ventilated infants may be of
      benefit. Whether ribavirin or corticosteroids reduce respiratory morbidity after
      RSV infection remains controversial. Immunoprophylaxis reduces RSV admissions,
      Palivizumab, a humanized monoclonal antibody, is a more cost-effective
      prophylaxis than RSV immune globulin. Nevertheless, the cost of prophylaxis,
      unless only given to very high-risk infants, exceeds savings made in reducing
      admissions.

PMID- 11981312
TI  - Pulmonary hydatid and other lung parasitic infections.
AB  - The lung may be infested by a great number of parasites. Hydatidosis is the most
      frequent parasitic lung disease. Diagnosis of lung hydatidosis is usually easy on
      chest radiography, ultrasonography, and CT scan, and immunodiagnosis may help in
      dubious cases. Surgery is necessary in most cases, but it must be conservative.
      Complex forms, such as disseminated disease and secondary lung hydatidosis
      (metastatic or bronchogenic) are difficult to treat and may be considered
      malignant. Medical treatment may be helpful in complex forms, in poor surgical
      risk patients, and in cases of preoperative spillage of hydatic fluid. Prevention
      programs are necessary in endemic areas, and research must be directed toward
      vaccination against the parasite. Other parasitic diseases are reported less
      frequently in the literature, and the majority of published articles are either
      case reports or only report a small number of cases. Clinical presentation is
      variable according to the great variety of parasites that may involve the lungs.

PMID- 11981314
TI  - Tumor necrosis factor-alpha antagonists for the treatment of rheumatic diseases.
AB  - Tumor necrosis factor-alpha (TNF-alpha) antagonists have rapidly emerged as a
      valuable class of antirheumatic agents. Etanercept, a dimerized version of the
      soluble tumor necrosis factor receptor II, and infliximab, a chimeric anti-TNF
      alpha monoclonal antibody, are currently approved for the treatment of rheumatoid
      arthritis (RA) based on their proven beneficial effects in clinical trials. New
      insights into the role of TNF-alpha in disease pathogenesis have expanded our
      understanding about the possible mechanisms by which these agents reduce synovial
      inflammation and inhibit bone and cartilage degradation. The enlarging safety
      experience has revealed growing concerns about TNF-alpha inhibition and increased
      risk for opportunistic infection, most notably the reactivation of latent
      Mycobacterium tuberculosis infection. Recent recommendations have addressed this
      risk by calling for pretreatment screening for previous exposure to tuberculosis.
      The success of etanercept and infliximab therapy for RA has prompted the
      development of other TNF-alpha antagonists and extended the investigation of this
      therapeutic approach to other inflammatory diseases. TNF-alpha antagonists
      promise to shape the care of RA and other rheumatic diseases for many years to
      come.

PMID- 11981315
TI  - Management of lupus erythematosus: recent insights.
AB  - This article reviews and cites only publications relating to the management of
      lupus that have appeared since 1999. The data in these publications demonstrate
      that preventive and proactive strategies are as important as medication in
      improving the quality of life and life span of the patient with lupus. The use of
      lasers and thalidomide represents major advances in cutaneous lupus. The first
      major study over 25 years using nonsteroidal anti-inflammatory drugs to manage
      lupus suggests benefits. Further evidence was presented showing that
      dehydroepiandrosterone, leflunomide, and methotrexate are effective in treating
      mild to moderate disease. Various iterations and modifications of traditional
      cyclophosphamide therapy with or without mycophenolate mofetil, cyclosporine, and
      azathioprine continue to be studied for treating organ-threatening disease.
      Intravenous gamma globulin and selective apheresis are niche therapies
      appropriate in a few, highly selected patients. Immunoablative doses of
      cyclophosphamide appear to be as effective as stem cell transplantation for
      serious disease resistant to conventional doses of cyclophosphamide. Twelve
      biologic agents have been studied in lupus since 1999, with only LJP-394 showing
      clear-cut, convincing efficacy.

PMID- 11981316
TI  - Stem cell transplantation for autoimmune disease: progress and problems.
AB  - The current status of stem cell transplantation in rheumatoid arthritis, juvenile
      chronic arthritis, systemic lupus erythematosus, and systemic sclerosis are
      reviewed. From a large European bone marrow transplant registry, a birds' eye
      view of stem cell transplantation for autoimmune disease can be obtained. Among
      43 rheumatoid arthritis patients, 35 juvenile chronic arthritis patients, 34
      systemic lupus erythematosus patients, and 58 systemic sclerosis patients who
      underwent stem cell transplantation, initial responses in most patients were good
      to excellent. Although initial transplant related mortality was low for
      rheumatoid arthritis, somewhat higher rates for juvenile chronic arthritis,
      systemic lupus erythematosus, and systemic sclerosis may be falling with
      modifications in the stem cell transplantation regimens. In rheumatoid arthritis
      and systemic lupus erythematosus treatment, the criteria for patient selection
      are still not clear and the therapeutic regimens for stem cell transplantation
      (and whether follow-up treatment is necessary) are not fully defined. In juvenile
      chronic arthritis, responses are encouraging although little fully published data
      beyond that from the European Bone Marrow Transplant Registry exist. In systemic
      sclerosis, criteria for patient selection and a limited number of stem cell
      transplantation regimens have been agreed on and controlled trials are underway.

PMID- 11981317
TI  - Specific cyclooxygenase-2 inhibitors: what have we learned since they came into
      widespread clinical use?
AB  - Specific inhibitors of cyclooxygenase-2 were introduced into widespread clinical
      use in 1999. Since that time, celecoxib and rofecoxib have become two of the most
      commonly prescribed medications in the United States. Clinical trials using these
      medications for arthritis and pain have uniformly demonstrated efficacy superior
      to that of placebo and similar to that of nonsteroidal anti-inflammatory drugs.
      However, controversy surrounding the proper place of cyclooxygenase-2 inhibitors
      in the hierarchy of treatment for arthritis continues, based primarily on their
      higher cost compared with that of acetaminophen and nonsteroidal anti
      inflammatory drugs. A decreased risk of gastrointestinal toxicity remains the
      primary justification for using the more expensive cyclooxygenase-2 inhibitors in
      preference to nonsteroidal anti-inflammatory drugs. The renal and cardiovascular
      effects of rofecoxib and celecoxib have been investigated in relation to
      nonsteroidal anti-inflammatory drugs and to one another. The data with respect to
      alteration in renal function, lower extremity edema, and hypertension indicates
      that cyclooxygenase-2 inhibitors affect the kidney in a manner similar to that of
      nonsteroidal anti-inflammatory drugs. The data comparing the cyclooxygenase-2
      inhibitors is difficult to interpret because it is not clear that comparable
      doses have been used in clinical trials. The potential thrombogenic risk of
      cyclooxygenase-2 inhibitors remains controversial, and conflicting data exist. It
      remains important to increase our understanding of the place of these agents in
      clinical practice from the perspective of efficacy, toxicity, and cost.

PMID- 11981318
TI  - Treatment of chronic hepatitis C infection with cryoglobulinemia.
AB  - Mixed cryoglobulinemia is characterized by a wide spectrum of manifestations that
      may vary from mild symptoms (such as purpura, arthralgias, and Raynaud
      phenomenon) to life-threatening conditions (such as acute abdomen, hyperviscosity
      syndrome, and renal involvement). Hepatitis C virus infection is considered the
      principal trigger of the disease. Therefore, the treatment not only should be
      tailored to the prevailing symptom but also take into account the presence of a
      chronic, often smoldering infection. Symptomatic therapies are to be used in
      cases of minor clinical manifestations and aggressive modalities in cases of life
      threatening conditions. The use of aggressive cytotoxic regimens should actually
      be stopped and every potentially immunosuppressive drug should be used with
      caution. Antiviral medications are used with growing frequency. To date, a few
      small trials with interferon-alpha alone or in combination with ribavirin in
      mixed cryoglobulinemia have been conducted. This overview deals with the current
      approach to the management of mixed cryoglobulinemia, focusing in particular on
      antiviral treatment in hepatitis C virus infection with or without mixed
      cryoglobulinemia.

PMID- 11981319
TI  - Treatment of the antiphospholipid syndrome.
AB  - Despite increasing knowledge of the immunology and pathophysiology of the
      antiphospholipid syndrome, treating this condition remains challenging. Because
      of a paucity of randomized controlled trials, many of the treatment
      recommendations are not evidence-based. Retrospective case series suggest that a
      high level of oral anticoagulation is needed to prevent recurrent thrombosis. The
      combination of heparin and low-dose aspirin is effective in significantly
      increasing the chances of a successful pregnancy in woman with recurrent
      pregnancy failure associated with antiphospholipid antibodies. Primary prevention
      with aspirin is justified in patients with antiphospholipid antibodies but
      without a prior history of thrombosis. Interesting and controversial issues in
      the treatment of the antiphospholipid syndrome include the use of less intensive
      anticoagulation or antiplatelet agents in some patient subsets, anticoagulation
      for certain nonstroke neurologic conditions, the role of other agents
      (hydroxychloroquine, antioxidants), and novel immunomodulatory strategies.

PMID- 11981321
TI  - Posttranslational protein modifications: new flavors in the menu of autoantigens.
AB  - Perhaps one of the most elusive areas of study in autoimmunity has been
      identifying the self-antigens that initially trigger the development of
      autoimmune responses. Recent work in this area has demonstrated that a number of
      biochemical modifications that arise in proteins after their translation induce
      autoimmune responses to otherwise ignored self-proteins. This article will
      describe those autoimmune diseases in which posttranslational modifications may
      play a role in initiation of disease, as well as identify how these modifications
      arise and contribute to the breakdown of immune tolerance. Lastly, we will
      address how posttranslational modifications in self-antigens affect current
      diagnostic techniques and the development of immunotherapies for autoimmune
      diseases.

PMID- 11981322
TI  - Autoantigenic posttranslational modifications of proteins: does it apply to
      rheumatoid arthritis?
AB  - There are many posttranslational modifications of proteins of which all are
      homeostatically important either to carry out a particular structural or
      functional role or to allow efficient recycling of the amino acid constituents.
      An important feature of the modified proteins is the acquisition of
      autoantigenicity. That notion should have been recognized for years with the
      modifications of immunoglobulin G that constitute new targets for rheumatoid
      factors. Citrullination or the deimination of arginine residues in proteins
      creates epitopes that are targeted by rheumatoid autoantibodies with a diagnostic
      sensitivity and specificity of 40% to 70% and 92% to 99%, respectively. The how,
      when, and why of the responsible break in tolerance are largely speculative but
      apoptosis, multiple genetic and environmental influences are likely required.
      Identifying citrullinated proteins as autoantigens has resulted in new diagnostic
      and prognostic autoantibody markers for RA and studying the citrullination
      process and its nature and role in cell biology has provided new insights into
      its pathogenesis.

PMID- 11981323
TI  - Genetics of rheumatoid arthritis: is there a scientific explanation for the human
      leukocyte antigen association?
AB  - Human leukocyte antigen genes associated with rheumatoid arthritis are commonly
      found in the unaffected population, implying that causal mechanisms of disease
      involve interactions between these genes and other factors. A variety of
      approaches-genetic, structural, and immunologic-are used to explore possible
      molecular interactions that may contribute to understanding the basis for this
      disease association. The specific relation between human leukocyte antigen-DR4
      alleles and rheumatoid arthritis remains one of the strongest and most thoroughly
      studied examples of human leukocyte antigen risk genes among human autoimmune
      disorders.

PMID- 11981324
TI  - Genetic approaches to the investigation of rheumatoid arthritis.
AB  - The investigation of genetic factors affecting the development or severity of
      rheumatoid arthritis may give new insights into the pathways involved in disease
      pathogenesis and lead to the identification of novel therapeutic targets.
      Recently, several novel approaches have been used in the attempt to unravel the
      complex association of rheumatoid arthritis with the human leukocyte antigen (
      HLA ) gene region. It is clear that non-HLA genes are also involved in disease
      pathogenesis, and identifying them remains a challenge. In the past year,
      considerable headway has been made in this field, and some interesting strategies
      have been used. This review summarizes the results of many of the HLA and non-HLA
      studies and tries to draw lessons from the investigation of genetic
      susceptibility factors in other complex diseases.

PMID- 11981325
TI  - Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid
      arthritis.
AB  - Clinical intervention studies have clearly shown the benefit in suppressing tumor
      necrosis factor-alpha (TNF-alpha) rheumatoid arthritis (RA). In consequence,
      considerable interest has arisen in those pathways that in turn regulate TNF
      alpha production, because they may offer further possible therapeutic targets.
      Several candidate pathways are currently being investigated. They include T
      cell/macrophage interactions mediated primarily through cell-cell membrane
      contact; novel cytokine activities; microbial-derived products, in particular
      bacterial deoxyribonucleic acid sequences; autoreactive T cells, and
      immunoglobulins. At the subcellular level, there is further interest in targeting
      signaling and mRNA processing and cytokine cleavage pathways required for optimal
      TNF-alpha production. The key recent observations in these areas, particularly in
      the extracellular compartment, are reviewed.

PMID- 11981326
TI  - Drug development in rheumatoid arthritis.
AB  - In the United States, therapies to treat rheumatoid arthritis and juvenile
      rheumatoid arthritis are approved and regulated by the Food and Drug
      Administration. This article explores certain aspects of the current Food and
      Drug Administration guidance for drugs, devices, and biologic products intended
      to treat these diseases (in this article, the term "drug" refers to any therapy
      in rheumatoid arthritis). Newer therapeutics are targeting not only important
      molecular pathways but also new labeling claims intended to represent clinically
      relevant outcomes. Questions regarding whether the risks of these new therapies
      are balanced by their effectiveness will evolve. The process of improvement in
      clinical trial design and metrics, along with improved therapies, will
      undoubtedly present both familiar and new challenges in the future.

PMID- 11981327
TI  - Gout and hyperuricemia.
AB  - Gout continues to be a health problem around the world despite the availability
      of effective therapies. Although the prevalence is influenced by genetic factors,
      the associations of alcohol consumption, obesity, and hypertension appear to be
      partially responsible for the increased prevalence of gout and hyperuricemia in
      African and Oriental countries. The association between hyperuricemia and
      cardiovascular disease seems linked to insulin resistance. This relation, in
      part, explains the common coexistence of hyperlipidemia and glucose intolerance
      in patients with gout. Accordingly, it is recommended that one pay more attention
      to dietary manipulation in patients with gout in addition to managing
      hypertension, obesity, and other medical problems. Although acute gout attacks
      can be treated, eliminating gout requires effective removal of urate from the
      body. Allopurinol remains a dominant urate-lowering agent, however its use may be
      limited by allergic reactions. Uricosuric agents are also effective urate
      lowering agents and provide an alternative to allopurinol. Strategies to treat
      patients who are sensitive to allopurinol continue to evolve.

PMID- 11981328
TI  - Animal models of pathologic calcification.
AB  - Recent progress in genetics and mouse genomics enables researchers to unveil the
      molecular basis for mouse phenotypes that express pathologic calcification in
      soft tissue and/or articular tissues. A newly identified multipass transmembrane
      protein, ANK, appears to function as an inorganic pyrophosphate (PPi) transporter
      or regulator of PPi transport. Abnormal extracellular PPi (ePPi) metabolism has
      been implicated in abnormal calcification, decreased concentrations predisposing
      to basic calcium phosphate (BCP) deposition, and increased concentrations
      promoting calcium pyrophosphate dihydrate (CPPD) crystal deposition in articular
      tissues. The chromosomal location of human ANK overlaps the locus identified in
      several kindreds affected with familial chondrocalcinosis. Deficient generation
      of ePPi by the ectoenzyme nucleoside triphosphate pyrophosphohydrolase also
      results in excessive ossification and ectopic deposition of BCP crystals in
      tiptoe-walking mice and PC-1 null mice. Recent studies reinforce the important
      regulatory role of ePPi in pathologic and physiologic calcification.

PMID- 11981329
TI  - Signaling mechanisms involved in crystal-induced tissue damage.
AB  - The association of crystal deposition with osteoarthritis and joint destruction
      is well established. Recent advances in understanding the mechanisms whereby
      calcium crystals contribute to cartilage damage are highlighted in this review.
      In vitro studies have shown that when calcium-containing crystals come in contact
      with cells they cause an influx in Ca 2+ concentration and activation of p42/44
      mitogen-activated protein kinases. This is followed by induction of proto
      oncogenes (c- fos, c- jun ) and induction of the nuclear transcription factors
      activator protein-1 and nuclear factor-kappaB, which in turn lead to crystal
      induced modulation of normal gene expression. Some of the downstream effects
      known to date include increased mitogenesis, up-regulation of members of the
      matrix metalloproteinase family, down-regulation of tissue inhibitor of
      metalloproteinase-1 and -2 in fibroblasts, induction of neutrophil chemotactic
      chemokines such as interleukin-8, activation and degranulation of neutrophils,
      and inhibition of neutrophil apoptosis. Because no known drug prevents or treats
      the consequences of basic calcium phosphate crystal deposition, an improved
      understanding of the molecular mechanisms leading to crystal-induced joint
      degeneration is essential to the development of a rational approach to target the
      consequences of crystal deposition.

PMID- 11981330
TI  - Calcium crystals in osteoarthritis.
AB  - Osteoarthritis is the most common form of arthritis in adults and its incidence
      increases with age. More than 50% of people aged 65 and older have radiographic
      changes of knee osteoarthritis. Calcium crystals, including calcium pyrophosphate
      dihydrate and basic calcium phosphate crystals, are also common in the elderly.
      Not surprisingly, osteoarthritis and crystal arthropathy frequently coexist. The
      question of a role for calcium crystals in causing or worsening osteoarthritis
      has been pondered for many years. Progress in understanding the
      interrelationships between calcium crystals and osteoarthritis has been slowed by
      our limited knowledge of the pathogenesis of both osteoarthritis and calcium
      crystal-induced arthritis and our limited ability to accurately detect calcium
      crystals. Nonetheless, there are good data from clinical and laboratory studies
      supporting an important role for calcium crystals in osteoarthritis.

PMID- 11981331
TI  - Counting cancers at the junction - a problem of routine statistics.
AB  - The increase over time in the incidence of cancer arising at the oesophagogastric
      junction has been the subject of many papers reviewing data obtained from cancer
      registries and other sources of routine statistics. The analysis of such data is
      beset with a number of problems, all of which compromise comparability over time
      and hence complicate interpretation. This makes it extremely difficult to assess
      with any degree of reliability the quantitative extent to which these cancers
      really are increasing. Some recent datasets, such as from the Eindhoven Cancer
      Registry, are now providing higher-quality information that can remedy this
      deficiency. In the absence of such routine information, useful insights can be
      obtained from analysis of appropriate clinical datasets that exist in Japan.

PMID- 11981332
TI  - Serological markers in inflammatory bowel disease: the pros and cons.
AB  - Accurate serological assays are desirable for the diagnosis of inflammatory bowel
      disease. Among several serological markers anti-Saccharomyces cerevisiae mannan
      antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly
      disease specific for Crohn's disease and ulcerative colitis, respectively.
      Combining the two improves their specificity. Sensitivity, however, is still low.
      Due to lack of standardization and vast interobserver variability, they cannot be
      used as the only diagnostic criteria but can assist clinicians in diagnosing and
      categorizing patients with inflammatory bowel disease as well as in helping them
      to take therapeutic decisions.

PMID- 11981333
TI  - Trends in reported adenocarcinomas of the oesophagus and gastric cardia in Japan.
AB  - Adenocarcinomas involving the oesophagus and gastric cardia are becoming more
      common in Western countries, but data from Japan are limited. We sought to
      determine whether the frequency of these cancers in Japan has increased in recent
      decades. Review of national cancer mortality data, national registries of
      oesophageal and gastric cancer cases, and records from two large cancer centres
      for various time periods between 1950 and 1998 did not show increased reporting
      of oesophageal adenocarcinomas. In contrast, both national and cancer centre data
      indicate an absolute increase in the number of gastric cancers involving the C
      area (proximal third of the stomach). From a national registry of resected
      primary gastric cancer cases, those arising in the C-area as a proportion of all
      tumours rose by 41.8% between 1963 (12.2% of all registered cases) and 1990
      (17.3%). Analysis of true cardia (<2 cm distal to oesophagus-cardia junction)
      early cancers from the two cancer centres showed significant increases in both
      absolute number and in proportion to other gastric cancers over a 36-year period.
      These data suggest that the frequency of cardia cancers is increasing in Japan.
      Lack of a parallel increase in oesophageal adenocarcinomas could be due to
      misclassification artefacts and/or coding preferences for gastro-oesophageal
      junction tumours.

PMID- 11981334
TI  - Increased incidence of adenocarcinomas at the gastro-oesophageal junction in
      Dutch males since the 1990s.
AB  - BACKGROUND: Worldwide population-based studies suggest that the incidence of
      oesophageal and gastric cardia adenocarcinomas has increased since the 1970s.
      OBJECTIVE AND METHODS: We studied time trends in mortality and incidence rates of
      oesophageal and gastric carcinomas according to subsite and histology in the
      south-east Netherlands since 1978. RESULTS: The age-adjusted mortality and
      incidence rates for oesophageal cancer doubled in males over the entire 19-year
      study period from 2.7 to 5.6 and from 2.4 to 4.8 per 100,000 person years,
      respectively. In females, a similar trend for the mortality and incidence rates
      was seen, but at a lower level. The age-adjusted mortality and incidence rates
      for gastric cancer decreased with time from 20.7 to 12.8 and from 21.6 to 15.9
      per 100,000 person years in males, respectively. In females, age-adjusted
      mortality and incidence rates for gastric cancer also decreased. Analysis of
      incidence rates by subsite and subtype showed an increase in adenocarcinomas of
      the oesophagus and gastric cardia, largely restricted to males. In females, the
      rise in incidence of squamous cell carcinoma of the oesophagus appeared to be
      more marked than the rise in adenocarcinomas, whereas the incidence of gastric
      cardia carcinomas has remained stable over the last 10 years. Neither the
      decrease in the number of unspecified tumours with time, nor the increase in the
      use of diagnostic endoscopy and imaging techniques, is likely to explain
      completely the observed increases. CONCLUSION: The increase in incidence of
      adenocarcinomas at the gastro-oesophageal junction in the south-eastern
      Netherlands seems, at least in part, to represent a true underlying increase that
      is restricted largely to males.

PMID- 11981335
TI  - Serological comparison of serum pepsinogen and anti-parietal cell antibody levels
      between Japanese and German patients.
AB  - BACKGROUND: Atrophic gastritis is more common in Japan than in Germany. The
      expression of anti-parietal cell antibody has been implicated in the genesis of
      atrophic gastritis associated with Helicobacter pylori infection. OBJECTIVE: We
      investigated the difference in serum levels of pepsinogens and in anti-parietal
      cell antibody expression between Japanese and German patients. METHODS: We
      recruited 102 Japanese and 46 German patients with dyspepsia. Endoscopic
      examination detected no localized lesions in the upper gastrointestinal tract of
      any patients. Anti-parietal cell antibody was investigated by enzyme-linked
      immunosorbent assay with the purified porcine H+,K+-ATPase fraction and
      immunohistochemistry. H. pylori infection was diagnosed by the presence of anti
      H. pylori antibody, by using the urease test and by histological examination.
      Serum levels of pepsinogen I and II and of gastrin were measured by a modified
      radioimmunoassay. RESULTS: Seventy-one Japanese (70%) and 17 Germans (37%) were
      positive for H. pylori. Serum levels of anti-parietal cell antibody were not
      significantly different between Japanese and Germans in both H. pylori negative
      and positive groups. The serum pepsinogen I/II ratio and gastrin levels were
      altered by H. pylori infection in both populations. Moreover, anti-parietal cell
      antibody levels were higher in H. pylori-positive patients with low pepsinogen
      levels than in those with high pepsinogen levels in both populations.
      CONCLUSIONS: The levels of anti-parietal cell antibody do not differ
      statistically between Japanese and Germans. Anti-parietal cell antibody might
      play a role in the progression of atrophic gastritis in both Japanese and German
      patients.

PMID- 11981336
TI  - Serological differentiation of inflammatory bowel diseases.
AB  - OBJECTIVE: In order to shorten the diagnostic procedures simple serological tests
      with high diagnostic value for Crohn's disease and ulcerative colitis are
      required. The aim of this study was therefore to evaluate the diagnostic value of
      a newly developed assay for the determination of antibodies to mannan of
      Saccharomyces cerevisiae in combination with antibodies to antigens of exocrine
      pancreas, goblet cells, human neutrophils and tissue transglutaminase. METHODS:
      Sera from 112 patients with Crohn's disease (82 confirmed and 30 suspected
      cases), 65 patients with ulcerative colitis, 13 patients with indeterminate
      colitis, 212 patients with other diseases and 250 healthy blood donors were
      tested for IgA and IgG antibodies to mannan of S. cerevisiae and IgA to tissue
      transglutaminase by enzyme-linked immunoassays. Endomysial IgA antibodies and
      antibodies to antigens of exocrine pancreas, goblet cells and human neutrophils
      were determined by indirect immunofluorescence. Sensitivity, specificity,
      positive and negative predictive values of antibodies to mannan of S. cerevisiae
      and different antibody combinations were determined regarding the diagnosis of
      Crohn's disease and ulcerative colitis. RESULTS: Antibodies to mannan of S.
      cerevisiae were detected in 50% of confirmed and 27% of patients suspected of
      having Crohn's disease. Among patients who did not have Crohn's disease only
      those suffering from gluten-sensitive enteropathy and primary biliary cirrhosis
      exhibited antibodies to mannan of S. cerevisiae (14%, 6%). With respect to
      antibody positivity, antibodies to mannan of S. cerevisiae and/or antibodies to
      antigens of exocrine pancreas combined with tissue transglutaminase antibody
      negativity yields a sensitivity, specificity, positive and negative predictive
      value of 60%, 100%, 100% and 90%, respectively, regarding diagnosis of Crohn's
      disease. CONCLUSIONS: Determination of antibodies to mannan of S. cerevisiae as a
      new marker for Crohn's disease is helpful for the differential diagnosis of
      inflammatory bowel disease. In combination with other established serological
      markers, antibodies to mannan of S. cerevisiae improve their diagnostic and
      predictive values considerably.

PMID- 11981337
TI  - Differential expression of cell adhesion molecules within inflamed ileal pouch
      mucosa: relationship to recruited cell subtypes.
AB  - INTRODUCTION: Endothelial-bound cell adhesion molecules are important in
      recruiting inflammatory cells to the mucosa in inflammatory bowel disease (IBD).
      Little is known of the expression of these molecules in relation to the
      recruitment of particular cell subtypes in the early course of mucosal
      inflammation. We therefore studied the expression of several adhesion molecules
      to examine their potential correlation with the cellular infiltrate in the
      inflamed ileal pouch, a possible disease model for ulcerative colitis. METHODS:
      Eleven patients (group 1) with familial adenomatous polyposis (FAP) with no
      evidence of ileal pouch inflammation and 14 patients (group 2) with ileal pouch
      inflammation (all with a prior diagnosis of ulcerative colitis) underwent pouch
      endoscopy with biopsy. Cryostat sections of biopsies were immunostained using a
      three-stage immunoperoxidase method for the adhesion molecules intercellular
      adhesion molecule (ICAM-1), vascular cellular adhesion molecule (VCAM-1), E
      selectin and mucosal addressin cell adhesion molecule 1 (MAdCAM-1). These results
      were correlated with immunostaining for the cell markers CD3, CD4, CD8, CD45RO,
      CD14 and CD15, which were quantified by computer image analysis. RESULTS: MAdCAM
      1, ICAM-1 and VCAM-1 were expressed to similar degrees on the endothelia of
      groups 1 and 2. In contrast, E-selectin was significantly increased in group 2 (P
      = 0.003) and correlated with immunostaining for CD15 (r = 0.72), CD4 (r = 0.55)
      and CD14 (r = 0.53). MAdCAM-1 expression did not correlate with any cell subset.
      CD15 was the only cell marker to be altered significantly, being increased in
      group 2 (P = 0.002). CONCLUSIONS: The inflammatory process seen in ileal pouch
      inflammation is characterized by up-regulation of E-selectin and recruitment of
      CD15-positive cells, emphasizing the role of neutrophil recruitment and migration
      to the epithelium in the pathogenesis of this condition.

PMID- 11981338
TI  - The constitutive expression of galectin-3 is downregulated in the intestinal
      epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases
      the level of galectin-3-specific mRNA in HCT-8 cells.
AB  - OBJECTIVE: Galectin-3, a lectin with specificity for beta galactoside, is
      expressed by a variety of cells, including intestinal epithelial cells. Among
      other functions, galectin-3 mediates cell adhesion and is involved in
      inflammatory processes. In this study, we assessed the expression of galectin-3
      in intestinal epithelial cells from Crohn's disease patients (n = 10), ileum
      adjacent to resected colon carcinoma (n = 9), unspecific bowel inflammation (n =
      1), diverticulosis (n = 1), ulcerative colitis (n = 3) and healthy jejunum used
      for interposition in larynx carcinoma (n = 1). The role of cytokines on galectin
      3 expression was a further aim of our study. METHODS: The galectin-3 distribution
      in intestinal epithelia was analysed by immunohistochemistry, immunoblotting,
      immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR).
      Human intestinal epithelial cell line (HCT-8) and primary cultured intestinal
      epithelial cells were treated with cytokines, and the effects on galectin-3
      expression were determined by RT-PCR. RESULTS: Galectin-3 showed a homogeneous
      distribution in epithelia from control patients. In contrast, in epithelial cells
      from Crohn's disease lesions, galectin-3 staining was strongly spotted and
      heterogeneous. In inflamed and reorganized tissue, galectin-3 expression was
      markedly reduced, and was associated with disintegration of epithelia. Primary
      cultured epithelial cells as well as HCT-8 cells expressed galectin-3 protein and
      mRNA. Incubation of HCT-8 cells with tumour necrosis factor alpha (TNF-alpha),
      but not with other cytokines, substantially reduced galectin-3 expression as
      shown by semiquantitative RT-PCR. CONCLUSIONS: Downregulation of galectin-3 in
      the intestinal epithelium of Crohn's disease patients may be a consequence of
      enhanced TNF-alpha production by inflammatory cells, thereby contributing to the
      pathophysiology of the disease.

PMID- 11981339
TI  - Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic
      patients: results of a multicentre pilot study.
AB  - OBJECTIVES: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis,
      leading to death in more than 90% of cases in the absence of liver
      transplantation. Several treatments have been attempted as a bridge to liver
      transplantation. Among such treatments, terlipressin has been studied in several
      reports, two prospective pilot studies and a double-blind, short-term, controlled
      haemodynamic study. Promising results have been shown with this drug. The purpose
      of this multicentre retrospective study was to evaluate the effects of
      terlipressin on renal function and survival of patients with HRS. PATIENTS AND
      METHODS: Eighteen patients recruited in three liver units with type 1 HRS in 16
      cases and type 2 HRS in two cases were given 4 mg/day terlipressin (range 1.5-12)
      for 7 days (range 2-16). Electrolytes, renal function, mean urinary output,
      natriuresis, liver function tests, and tolerance of the treatment were monitored
      regularly. RESULTS: A total of 13/18 (72%) patients responded with a mean decline
      in serum creatinine ranging from 31 to 75% from day 0 to day 5. Eight of these 13
      patients had a normal serum creatinine level at day 5. Liver function tests
      remained unaffected by terlipressin administration. Three local necrosis
      complications were noted in patients receiving terlipressin continuously via an
      infusion pump. Two responder patients survived: one of these underwent orthotopic
      liver transplantation with a follow-up of 24 months; the other is alive with a
      follow-up of more than 36 months. Patients who responded to terlipressin had
      lower baseline serum bilirubin and significantly higher serum sodium
      concentrations than patients who did not respond. CONCLUSION: In this pilot
      study, improvement in renal function was noted in 72% of cases after
      administration of terlipressin, and was associated with long-term survival in two
      patients. Parameters associated with response to terlipressin and increased
      survival should be defined better in a large cohort of cirrhotic patients with
      HRS.

PMID- 11981340
TI  - Detection of nodules in liver cirrhosis: spiral computed tomography or magnetic
      resonance imaging? A prospective study of 88 nodules in 34 patients.
AB  - Detection and characterization of all focal lesions in the liver are critical for
      screening patients with chronic liver disease. The aim of this prospective study
      was to investigate the accuracy of magnetic resonance imaging (MRI) and spiral
      computed tomography for the diagnosis of hepatic nodules in cirrhotic patients
      when compared with pathological findings of the explanted liver. From February
      1997 to July 1999, 34 cirrhotic patients waiting for orthotopic liver
      transplantation (OLT) (mean age, 53.5 +/- 9.3 years; 24 males) were included. All
      patients had MRI and spiral computed tomography examinations, and findings were
      matched with the histological findings. Data analyses were made using the McNemar
      chi-square test. Mean time between radiological examination (MRI or spiral
      computed tomography) and OLT was 43.8 +/- 39 days. A total of 88 nodules were
      found in the 34 patients: 54 hepatocellular carcinoma (HCC) (mean size, 18 +/- 10
      mm) in 21 patients, 22 dysplastic nodules (mean size, 10.7 +/- 4.3 mm) in 11
      patients, and 12 macroregenerative nodules in 13 patients. Lesion-by-lesion
      analyses showed that sensitivity of MRI and spiral computed tomography for
      nodule, HCC or dysplastic nodule diagnosis was 44.3 and 31.8% (P = 0.02), 61.1
      and 51.9% (P = 0.2), and 27.3 and 0% (P = 0.04), respectively. Patient-by-patient
      analyses showed no statistical difference between spiral computed tomography and
      MRI for nodule diagnosis. In conclusion, in patients with liver cirrhosis, MRI is
      more accurate than spiral computed tomography for the detection of liver nodules
      and dysplastic nodules. However, tumour size is always a restricting factor for
      these two techniques, which are unable to detect small HCC in more than 60% of
      cases.

PMID- 11981341
TI  - Hepatic arterial blood flow in large hepatocellular carcinoma with or without
      portal vein thrombosis: assessment by transcutaneous duplex Doppler sonography.
AB  - BACKGROUND: As liver cirrhosis progresses, the portal venous blood (PVBF) flow
      decreases, accompanied by an increase in hepatic arterial blood flow. Large
      hepatocellular carcinoma is a hypervascular tumour with a rapid growth, which
      seems to require an increase of the tumoral arterial blood flow. Furthermore,
      hepatocellular carcinoma is frequently associated with portal vein thrombosis,
      which subsequently impedes portal blood supply. METHODS: The purpose of our study
      was to estimate alterations in the hepatic arterial blood flow in large
      hepatocellular carcinomas occurring in liver cirrhosis, in comparison with liver
      cirrhosis and controls. Liver blood flow measurements were determined by duplex
      Doppler sonography in 47 patients with large hepatocellular carcinomas (13 with
      portal vein thrombosis and 34 without this thrombosis), 42 liver cirrhosis
      patients and 30 controls. The Doppler perfusion index was calculated as the ratio
      of hepatic arterial blood flow to total hepatic blood flow. RESULTS: The patients
      with liver cirrhosis had a significant increase of hepatic arterial blood flow as
      compared to controls (P < 0.001), accompanied by a significant reduction in PVBF
      (P < 0.005). As a result, the Doppler perfusion index was increased in patients
      with liver cirrhosis as compared to controls (P < 0.001). The hepatic arterial
      blood flow was increased in patients with hepatocellular carcinoma but without
      portal vein thrombosis as compared to the cirrhotic patients (P < 0.001), with a
      significant reduction of PVBF (P < 0.001). Hepatic arterial blood flow was also
      increased in patients with both hepatocellular carcinoma and portal vein
      thrombosis as compared to the patients without this thrombosis (P < 0.001).
      CONCLUSION: These results suggest that in large hepatocellular carcinomas there
      is a decreased PVBF, accompanied by an increased hepatic arterial blood flow. The
      hepatic arterial buffer response seems to be active in hepatocellular carcinomas
      and maintains liver perfusion to adequate levels.

PMID- 11981342
TI  - Red cell distribution width as a marker of coeliac disease: a prospective study.
AB  - BACKGROUND: Coeliac disease is frequently underdiagnosed because of its protean
      presentations. Serological tests may be helpful in screening programmes for
      populations at risk, but they are costly. AIM: To determine prospectively whether
      a commonly available haematological test such as the red cell distribution width
      (RDW) could be of help in detecting unrecognized coeliac disease. METHODS: Of 353
      consecutive adult patients referred to our outpatient malabsorption clinic, 198
      in whom clinical suspicion was strong were referred for further investigations
      and intestinal biopsy. Seventy-six inflammatory bowel disease outpatients and 90
      subjects admitted for diseases other than malabsorption were enrolled as the
      control group. RESULTS: RDW was increased in 94 (47.4%) and normal in 104 (52.5%)
      of 198 patients. Duodenal biopsy confirmed coeliac disease in 80 (85.1%) of the
      former patients and 69 (66.3%) of the latter patients. No correlation between RDW
      values and histological scores was found. Overall RDW increase was found in
      80/149 (53.7%) patients with a definite diagnosis of coeliac disease, and in
      14/49 (28.6%) patients in whom biopsy excluded the disease. A 1-year gluten
      withdrawal led to a significant decrease in RDW value, even in patients with
      obdurate mucosal impairment. CONCLUSIONS: In patients in whom there is a strong
      clinical suspicion of coeliac disease, an elevated RDW despite normal haemoglobin
      concentration may be a reliable predictor of the disease.

PMID- 11981343
TI  - High-grade dysplasia and invasive carcinoma in colorectal adenomas: a
      multivariate analysis of the impact of adenoma and patient characteristics.
AB  - BACKGROUND AND AIMS: Most colorectal carcinomas develop from preformed adenomas,
      but only a minority of adenomas undergo malignant transformation. The clinical
      significance of polyps of size < 0.5 cm is controversial. The primary goal of
      this study was to assess the independent risk factors of adenoma and patient
      characteristics associated with advanced pathological features (APF; i.e. high
      grade dysplasia or invasive carcinoma) in colorectal adenomas. A secondary goal
      was to assess the malignant potential of adenomas with a diameter of < 0.5 cm.
      PATIENTS AND METHODS: Patients who underwent total colonoscopy at our Medical
      Department between 1978 and 1996 and had at least one colorectal adenoma were
      considered for this study. Patients with a history of colorectal cancer, prior
      polypectomy or colorectal surgery were excluded. A total of 7590 adenomas removed
      from 4216 patients were included in this analysis. Logistic regression analysis
      was used to study the impact of different adenoma and patient characteristics on
      the risk of APF. RESULTS: Size proved to be the most important risk factor for
      APF. The percentage of adenomas with APF was 3.4%, 13.5% and 38.5% for adenomas
      of diameter < 0.5 cm, 0.5-1 cm and > 1 cm, respectively. Villous or tubulovillous
      histology, left-sided location and age >or= 60 years were also associated with
      APF, whereas sex and number of adenomas had no significant impact. Logistic
      regression analysis revealed that the risk of an adenoma containing APF was best
      described by a model incorporating the factors size, location, age, and the age
      by histology interaction. In the class of adenomas with diameter < 0.5 cm, no
      invasive carcinoma was found, but 3.4% of adenomas had high-grade dysplasia.
      CONCLUSIONS: The risk of a colorectal adenoma containing APF can be estimated
      only by a complex model taking into account several adenoma and patient
      characteristics. Size, histological type, location and age are independent risk
      factors for APF in colorectal adenomas. As a considerable percentage of adenomas
      with diameter < 0.5 cm contain high-grade dysplasia, the clinical conclusion from
      our study is that all adenomas, including those with diameter < 0.5 cm, should be
      removed whenever possible.

PMID- 11981344
TI  - Recurrent bacterial cholangitis due to a juxtapapillary diverticulum.
AB  - We present a patient with recurrent bacterial cholangitis. Endoscopic retrograde
      cholangiopancreatography did not show evidence for choledocholithiasis or
      obstructing abnormalities of the common bile duct. However, a juxtapapillary
      diverticulum was situated at the edge of the papilla of Vater. We postulate that
      a juxtapapillary diverticulum can obstruct biliary flow due to its anatomical
      relation with the papilla, which may predispose to bacterial cholangitis. This
      might be prevented by sphincterotomy of the papilla.

PMID- 11981345
TI  - Co-existence of a huge pseudocyst and mucinous cystadenoma: report of a case and
      the value of magnetic resonance imaging for differential diagnosis.
AB  - Co-existence of a pancreatic pseudocyst and a neoplastic cyst is rare and their
      differential diagnosis is difficult if the patient has an atypical history as
      well as subclinical symptoms. The formation of a pseudocyst under such
      circumstances is usually the result of downstream ductal obstruction by the
      neoplasm. Two large cysts were found in a 43-year-old woman who had symptoms of
      gastric outlet obstruction that were the result of external compression by one of
      the cysts. Magnetic resonance imaging was superior to computed tomography,
      discriminating between the internal contents and surrounding tissue of the two
      cysts, enabling the correct preoperative diagnosis of a pseudocyst co-existing
      with a mucinous cystadenoma to be made. It was most unusual for the pseudocyst to
      be located downstream of the mucinous tumour, ruling out ductal obstruction by
      the tumour in its pathogenesis. A possible explanation for the pseudocyst
      formation in this case was pancreatic juice accumulation in the space of the
      lesser sac after pancreatic parenchymal destruction by the mucinous tumour.

PMID- 11981346
TI  - Prospects for the temporary treatment of acute liver failure.
AB  - At present, the most successful treatment of acute liver failure is orthotopic
      liver transplantation, with survival rates ranging from 70% to 85%. However,
      mortality rates for liver failure remain high because of the shortage of
      available donor organs. Therefore, there has been renewed interest in temporary
      treatment methods for patients with acute liver failure to either allow liver
      regeneration or await liver transplantation. It is thought that the function of
      the liver can only be replaced with the biological substrate, e.g. liver cells or
      a whole liver specimen, which requires the availability of liver tissue from
      xenogeneic or human sources. In this review, existing temporary liver support
      techniques are summarized and the potential hazards are described. These include
      the immunological implications of these techniques, e.g. the host versus graft
      reaction, which may influence the effectivity of the support system, and in the
      long run may sensitize the patient to subsequent allogeneic transplantation. The
      graft versus host reaction is also considered. At present, one of the major
      concerns is the threat of pig-to-human transmission of activated endogenous
      retrovirus present in the pig genome. An overview is given of literature
      concerning the transmission of retrovirus particles in vitro and in vivo.
      Finally, new solutions for the development of ex vivo systems for temporary
      treatment of patients with acute liver failure are discussed. These include the
      use of new immortalized human cell lines and human fetal hepatocytes, and the
      possibility of isolating, expanding and genetically manipulating stem cells in
      order to have stable differentiated and committed cells.

PMID- 11981349
TI  - Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled
      study in depression in primary care.
AB  - Escitalopram, a selective serotonin reuptake inhibitor (SSRI), was compared to
      placebo in a study of patients with major depressive disorder (DSM-IV) who had
      baseline Montgomery-Asberg Depression Rating Scale (MADRS) total scores >or=22
      and <or=40. After a 1-week, single-blind placebo period, patients were randomized
      to receive escitalopram 10 mg/day (n=191) or placebo (n=189) in an 8-week, double
      blind period. The primary efficacy analysis of adjusted mean change in MADRS
      total score from baseline showed a statistically significantly larger effect for
      escitalopram than for placebo with a treatment difference at week 8 (last
      observation carried forward, LOCF) of 2.7 points (SE 0.85; P=0.002). In further
      by-week efficacy analyses, the effect of escitalopram was consistently larger
      than that of placebo (P<0.05) beginning at week 1 (Clinical Global Impression
      Improvement score), week 2 (MADRS score) or week 3 (Clinical Global Impression
      Severity score). Escitalopram was very well tolerated with a low overall
      withdrawal rate similar to that for placebo. Nausea was the only adverse event
      reported significantly more in escitalopram-treated patients than in placebo
      treated patients, although it was infrequent and transient. Escitalopram 10
      mg/day had a statistically significantly better antidepressant effect than
      placebo as early as week 1, and was safe and very well tolerated.

PMID- 11981350
TI  - Treatment of generalized anxiety disorder with citalopram.
AB  - Serotonin reuptake inhibitors (SSRI), such as venalafaxine and paroxetine, are
      used in the treatment of generalized anxiety disorder (GAD). Patients with GAD
      frequently have comorbid psychiatric disorders, such as depression. SSRIs are
      effective in the treatment of a variety of anxiety disorders and depression.
      Citalopram, a newer SSRI used in the treatment of depression, has not been
      studied for GAD. This is the first report of the use of citalopram, the most
      selective SSRI, for the treatment of GAD in a retrospective case observation
      study. Thirteen patients diagnosed with GAD were treated with citalopram at an
      academic outpatient clinic. The main outcome measures were the Hamilton Rating
      Scale for Anxiety (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Clinical
      Global Impressions of Severity (CGI-S; at baseline) and Improvement (CGI-I). The
      mean age of the patients was 38 years. The mean dose of citalopram at endpoint
      was 33 mg/day (range 10-60 mg/day). After 12 weeks of treatment with citalopram,
      all 13 patients experienced full or partial improvement in GAD and depressive
      symptoms leading to meaningful improvement in social and occupational
      functioning. Mean baseline HAM-A scores (mean+/-SEM) decreased from 22.2+/-1.3 to
      6.2+/-0.9 after citalopram treatment. The mean CGI-I score was 1.8+/-0.2 with 11
      of the 13 patients responding (CGI-I of 1 or 2). These data suggest that
      citalopram may be an effective treatment for GAD. Several patients who had failed
      previous treatment with other SSRIs responded to citalopram, suggesting that a
      second SSRI, such as citalopram, may be beneficial in this population. A larger
      placebo-controlled study of citalopram is warranted in GAD.

PMID- 11981351
TI  - The adequacy of pharmacotherapy in outpatients with obsessive-compulsive
      disorder.
AB  - Pharmacotherapy and behavioural treatment are the main treatment options for
      patients with obsessive-compulsive disorder (OCD). Nevertheless, studies on the
      appropriateness of these treatments are scarce. We aimed to assess the adequacy
      of treatment in general, and pharmacotherapy in particular, in patients with OCD.
      Three hundred and thirteen outpatients with OCD were interviewed on admission at
      the University Medical Center (UMC) Utrecht, The Netherlands. Patients were
      evaluated for demographic and clinical characteristics. Current treatment was
      assessed on admission and treatment history was appraised retrospectively. On
      admission, only one-half of the patients took appropriate medication, of which
      7.6% were prescribed maximal effective doses, 11.8% mean effective doses, 15%
      minimal effective doses and 19.4% ineffective doses. Approximately 35% of
      patients were prescribed no drugs and 16% inappropriate drugs. Although the
      majority of the patients had been treated on average three times prior to their
      current treatment, 24% had never received a serotonin reuptake inhibitor (SRI) or
      behaviour therapy. For approximately 50% of the total sample, the maximal
      effective dose of SRIs had never been taken during the course of treatment
      history. A large proportion of patients with OCD fail to receive adequate
      treatment. Many patients were prescribed SRIs at doses below those recommended
      for the guidelines.

PMID- 11981352
TI  - Quetiapine augmentation in patients with treatment resistant obsessive-compulsive
      disorder: a single-blind, placebo-controlled study.
AB  - Recently, atypical antipsychotics have been used for the management of the
      patients with refractory obsessive-compulsive disorder (OCD). The aim of the
      present study was to evaluate the results of quetiapine augmentation to a
      serotonin reuptake inhibitor (SRI) in the patients with refractory OCD. Fifty-two
      patients with OCD according to DSM-IV entered 3 months of an open-label phase
      treatment with a SRI with or without concomitant adjunctive treatment regimen. Of
      them, 27 patients were refractory OCD. These patients were randomly divided into
      two groups, SRI plus quetiapine and SRI plus placebo, for an 8-week single-blind
      phase. The course of OCD was evaluated by Yale-Brown Obsession-Compulsion (Y
      BOCS) and Clinical Global Impression-Severity of Illness and Improvement (CGI-SI
      and I) Scales every other week for 8 weeks. Of the 14 patients in group I, nine
      (64.4%) showed significant improvement with 60% or greater improvement on the Y
      BOCS and one (7.1%) partial improvement with 30% or greater improvement on the Y
      BOCS, whereas no improvement was observed in group II. The addition of quetiapine
      to ongoing SRI therapy has been found to be effective and well-tolerated approach
      in patients with refractory OCD.

PMID- 11981353
TI  - Therapeutic effects of milnacipran, a serotonin and noradrenaline reuptake
      inhibitor, on post-stroke depression.
AB  - Depression is common after stroke. While several reports have been published on
      the use of antidepressants such as selective serotonin reuptake inhibitors and
      tricyclics for the treatment of post-stroke depression (PSD), no previous study
      has examined the use of a selective serotonin and noradrenaline reuptake
      inhibitor (SNRI) for this condition. The present study investigated the efficacy
      and safety of milnacipran, a SNRI, for the treatment of PSD. A 6-week open study
      was conducted in 12 patients (two males and 10 females) aged 53-88 years. All
      patients were diagnosed with major or minor depressive disorder according to DSM
      IV, where onset was subsequent to a cerebral infarction or haemorrhage (stroke).
      Severity of depression was assessed using the 21-item Hamilton rating scale for
      depression (HAM-D). The maximum total daily dose of milnacipran was in the range
      of 30-75 mg b.i.d. Three patients experienced side-effects, but none of the side
      effects were serious. Two patients dropped out of the study. At the end of the
      study, 58.3% (7/12) of the total patient population and 70% (7/10) of the
      patients completing the study were in remission (a final HAM-D score of less than
      7 and no longer meeting criteria for major or minor depression). These results
      suggest that milnacipran may be an effective treatment for PSD.

PMID- 11981354
TI  - Impairment of constructive memory in schizophrenia.
AB  - Episodic memories are characterized by a specific state of awareness, conscious
      recollection, which allows subjects to mentally relive past events. They are not
      a literal reproduction of the past but instead depend on constructive processes.
      Patients with schizophrenia exhibit a specific impairment of conscious
      recollection. The aim of this study was to investigate the role of constructive
      processes into defective conscious recollection of patients with schizophrenia.
      An experiential approach to false recognition and related states of awareness was
      used. Thirty patients with schizophrenia, who were matched with 30 normal
      subjects, studied lists of words semantically related to a non-presented theme
      word (critical lure). On a recognition memory task with both previously presented
      words and non presented critical lures, they were asked to give Remember, Know or
      Guess responses to items that were recognized on the basis of conscious
      recollection, familiarity or guessing, respectively. Patients with schizophrenia
      recognized fewer studied words and critical lures than normal subjects. This
      deficit was restricted to memories associated with conscious recollection as
      indicated by a decrease in Remember responses, but not Know and Guess responses.
      Our results indicate that patients with schizophrenia exhibit an impaired
      conscious recollection, whether memories are true or false. They provide evidence
      that schizophrenia impairs the mere construction of conscious recollection.

PMID- 11981355
TI  - Depot antipsychotic preparations in schizophrenia: the state of the economic
      evidence.
AB  - Depot treatment of schizophrenia - to date restricted to conventional
      antipsychotic medications - remains widespread. Whilst there have been numerous
      studies of clinical effectiveness, and systematic reviews of the accumulated
      evidence, little appears to be known about the cost-effectiveness of depot
      treatment. A systematic review was conducted of the international literature in
      an attempt to find, appraise and summarize the economic evaluative evidence. Very
      few studies of relevance or quality could be found. Most of the papers purporting
      to examine the economic consequences of depot treatment were methodologically
      weak. There were no randomized controlled trials of depot vs. oral
      antipsychotics, the few mirror-image studies were uncontrolled and a single
      naturalistic observational study measured costs only narrowly. Two modelling
      studies - which have a number of limitations because of their partial reliance on
      expert opinion rather than observational data - suggest that depot treatment may
      lower costs and improve cost-effectiveness. Overall, however, it is not possible
      to draw conclusions as to the cost-effectiveness of depot conventional
      antipsychotic treatment for schizophrenia.

PMID- 11981356
TI  - Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or
      olanzapine.
AB  - Plasma levels of clozapine and olanzapine are lower in smokers than in
      nonsmokers, which is mainly due to induction of cytochrome P4501A2 (CYP1A2) by
      some smoke constituents. Smoking cessation in patients treated with antipsychotic
      drugs that are CYP1A2 substrates may result in increased plasma levels of the
      drug and, consequently, in adverse drug effects. Two cases of patients who smoked
      tobacco and cannabis are reported. The first patient, who was receiving clozapine
      treatment, developed confusion after tobacco and cannabis smoking cessation,
      which was related to increased clozapine plasma levels. The second patient, who
      was receiving olanzapine treatment, showed important extrapyramidal motor
      symptoms after reducing his tobacco consumption. The clinical implication of
      these observations is that smoking patients treated with CYP1A2 substrate
      antipsychotics should regularly be monitored with regard to their smoking
      consumption in order to adjust doses in cases of a reduction or increase in
      smoking.

PMID- 11981357
TI  - Immunologic reconstitution after 1 year of highly active antiretroviral therapy,
      with or without protease inhibitors.
AB  - OBJECTIVES: To assess the effectiveness of two triple antiretroviral combinations
      (2 nucleoside reverse transcriptase inhibitors [NRTIs] + 1 protease inhibitors
      [PI] vs. 2 NRTIs + 1 nonnucleoside reverse transcriptase inhibitor [NNRTI]) to
      correct T-cell subsets abnormalities and to restore immune functions in
      asymptomatic antiretroviral-naive HIV-1-infected patients with a baseline CD4 T
      cell counts >500/mm3 and plasma viral load >5000 copies/mL. DESIGN AND METHODS:
      Twenty randomized patients from 2 cohort studies receiving either stavudine (d4T)
      + lamivudine (3TC) + indinavir (n = 9), or d4T + didanosine (ddI) + nevirapine
      (NVP) (n = 11) were studied. Viral load, T-cell subsets and T-cell functions were
      analyzed at baseline and after 1 year of treatment. RESULTS: After 1 year of
      follow-up, the PI regimen was significantly more effective in reducing plasma and
      lymphoid tissue VL to undetectable levels. A significant increase in CD4+ T cells
      was observed in patients treated with PI (p =.0007) compared with those treated
      with NVP. Percentages of CD8+ T-cells and of activated CD8+ T-cells (CD38+ and
      DR+ as well as memory CD45RO+) decreased in all patients. An increase of the
      CD28+ subset of CD8+ T-cells also occurred in both groups of treatment. Naive T
      cells were maintained in the CD4+ subset and augmented in the CD8+ subset in all
      patients. In both PI and NVP groups, memory CD4+ T-cells increased significantly
      (p =.03). Peripheral blood mononuclear cell responsiveness to polyclonal stimuli
      and to tetanus toxoid and cytomegalovirus (CMV) antigen was similar in both
      groups of treatment. HIV-infected patients treated for 1 year with both triple
      combinations lacked significant T-cell responsiveness to HIV-1 proteins.
      CONCLUSIONS: These data suggest that immune reconstitution achieved after 1 year
      of therapy with PI-containing or PI-sparing regimens is similar, despite the
      higher effectiveness of PI-containing regimens in reducing viral load. Additional
      therapeutic approaches should be designed to restore HIV-1-specific responses.

PMID- 11981358
TI  - Maternal HIV-1 antibody and vertical transmission in subtype C virus infection.
AB  - The role of maternal humoral immune response and viral load was analyzed in
      relation to the incidence of mother-to-child transmission (MTCT) of infants born
      to HIV-1 subtype C infected mothers. High levels of viral RNA in the serum
      correlated with MTCT as did high titers of subtype C consensus V3 peptide binding
      antibodies (BA) and neutralizing antibody (NA) to subtype B HIV-1MN. Logistic
      regression analysis showed that maternal viral load and V3 peptide subtype C BA
      were independent predictors for MTCT, odds ratio (OR) = 2.22 and OR = 2.52,
      respectively. No correlation between NA to homologous HIV-1 subtype C virus and
      MTCT was found. BA to V3 peptides may provide a rapid inexpensive method that can
      be used to determine the risk of HIV-1 MTCT.

PMID- 11981359
TI  - Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor
      containing highly active antiretroviral therapy.
AB  - Decreased insulin sensitivity, hyperlipidemia, and body fat changes are
      considered as risk factors for coronary heart disease (CHD). A clustering of such
      factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired
      fibrinolysis and increased coagulation are additional independent risk factors
      for CHD. We studied the effects of protease inhibitor (PI)-containing highly
      active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in
      363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and
      97 were treatment naive. The fasting plasma levels of insulin, glucose,
      triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and
      fibrinogen were evaluated together with the areas of visceral adipose tissue and
      the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of
      insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol;
      visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein
      ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were
      significantly increased in patients receiving PI-containing HAART compared with
      treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly
      higher in patients receiving PI-containing HAART. PAI-1 levels were higher in
      individuals with MSDR but also in patients without MSDR who were receiving PI
      containing HAART. PAI-1 was independently correlated to use of PI-containing
      HAART, triglyceride level, insulin level, and body mass index (p <.001). These
      findings suggest that patients receiving PI-containing HAART have decreased
      fibrinolysis and increased coagulability, which may thus represent additional
      risk factors for cardiovascular disease in this patient group.

PMID- 11981360
TI  - Bone mineral content is lower in prepubertal HIV-infected children.
AB  - Total body bone mineral content (TBBMC) was measured by dual energy x-ray
      absorptiometry in a cross-sectional study of 51 prepubertal HIV-infected children
      and 262 healthy prepubertal children aged 4.2 to 14.7 years. The mean TBBMC +/-
      SD was lower in HIV-positive children than in HIV-negative controls (955 +/- 325
      vs. 1,106 +/- 273 g, respectively; p =.0006). Reductions in TBBMC remained in the
      HIV-positive group after adjusting for age, sex, and race by analysis of
      covariance (p <.001). Differences in TBBMC between HIV-positive and HIV-negative
      groups persisted when height and weight were also accounted for in the analysis
      (p =.027). The magnitude of the difference in TBBMC between the groups increased
      with age. In the HIV-positive group, no associations were observed between TBBMC
      and use of a protease inhibitor, duration of treatment with antiretroviral
      medications, viral load, or CD4 cell count. TBBMC is decreased in HIV-infected
      children. As a result of compromised bone mineral accrual, HIV-infected children
      may be at increased risk for osteoporosis and related complications.

PMID- 11981361
TI  - Dose-escalating study of the safety and pharmacokinetics of nelfinavir in HIV
      exposed neonates.
AB  - The pharmacokinetics of nelfinavir (NFV) in neonates younger than 4 weeks of age
      was assessed. Three cohorts of HIV-exposed neonates were enrolled in cohorts to
      receive 15, 30, and 45 mg of NFV/kg twice daily in combination with stavudine and
      didanosine for 4 weeks after birth. Trough NFV concentrations (C(min)) were
      measured at 1 and 7 days of age. Intensive pharmacokinetic evaluations were
      performed at 14 and 28 days of age. The median NFV C(min) values in the 15 mg/kg
      (6 patients), 30 mg/kg (5), and 45 mg/kg (11) cohorts at 1, 7, 14, and 28 days of
      age were 0.19, 1.21, 0.51, and 0.33; 1.02, 3.18, 0.73, and 0.55; and 0.67, 3.21,
      0.70, and 0.73 mg/L, respectively. The median area under the plasma concentration
      versus-time curve values over 12 hours in the three cohorts at 14 and 28 days of
      age were 14.4 and 8.7, 19.4 and 15.8, and 23.4 and 18.5 (h. mg)/L, respectively.
      No serious adverse events were observed. In conclusion, the systemic exposure of
      NFV decreased after 7 days of age, possibly because of hepatic enzyme maturation,
      autoinduction of NFV metabolism, and/or changes in NFV absorption. The highly
      variable systemic exposure observed in the study indicates that therapeutic drug
      monitoring seems warranted to ensure adequate NFV dosing in this population.

PMID- 11981362
TI  - Simplifying protease inhibitor therapy with once-daily dosing of saquinavir soft
      gelatin capsules/ritonavir (1600/100 mg): HIVNAT 001.3 study.
AB  - OBJECTIVE: To determine the feasibility of switching therapy for HIV-1-infected
      patients with plasma viral loads of <50 HIV-1 RNA copies/mL who are receiving
      twice-daily saquinavir soft-gelatin capsules (SQV-SGC) plus dual nucleoside
      reverse transcriptase inhibitors (NRTIs) to a regimen containing once-daily SQV
      SGC/ritonavir (RTV). DESIGN: Therapy for patients with plasma viral loads of <50
      copies/mL after 2 years of treatment with twice-daily SQV-SGC (1400 mg) plus
      zidovudine/lamivudine or didanosine/stavudine was switched to once-daily SQV
      SGC/RTV (1600/100 mg) with continuing NRTI treatment. METHODS: Safety and
      efficacy (determined by plasma viral load and CD4 cell count) were evaluated
      (week 24). For 12 patients, steady-state plasma pharmacokinetics of SQV was
      determined (week 4). RESULTS: Once-daily SQV-SGC/RTV was well tolerated. No
      patient changed regimens. After 24 weeks, 64 (93%) of 69 patients had plasma
      viral loads of <50 copies/mL (the remaining 5 patients had plasma viral loads of
      <300 copies/mL). The median CD4 cell count increased from 534/mL at the start of
      once-daily SQV-SGCs/RTV to 695/mL after 24 weeks (p <.001). Compared with the
      preceding 24 weeks of treatment with twice-daily SQV-SGC, the CD4 cell count
      improved significantly during once-daily SQV-SGC/RTV therapy (p <.001). All
      patients maintained SQV trough concentrations (C(24h)) of >0.05 mg/L. Median
      values for the area under the plasma concentration-versus-time curve from 0 to 24
      hours (AUC(0-24h)), maximal concentration (C(max)), and C(24h) for SQV were 48.1
      (h.mg)/L, 6.98 mg/L, and 0.17 mg/L, respectively. Body weight was inversely
      correlated with SQV AUC(24h) and C(24h) (p <.01). CONCLUSIONS: Clinical and
      pharmacokinetic data support once-daily SQV-SGC/RTV (1600/100 mg) with two NRTIs
      as a convenient and safe therapeutic regimen to maintain viral suppression and
      immune function in HIV-1-infected patients with plasma viral loads of <50
      copies/mL.

PMID- 11981363
TI  - Pharmacokinetic interaction between nevirapine and ethinyl
      estradiol/norethindrone when administered concurrently to HIV-infected women.
AB  - OBJECTIVE: To determine the effects of nevirapine (NVP), a nonnucleoside reverse
      transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK)
      of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive,
      and to assess the effects of EE/NET on the steady-state PK of NVP. METHODS: Ten
      HIV-1-infected women underwent intensive PK sampling after single-dose
      administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15),
      followed by 200 mg twice daily (days 16-29), was added to background potent
      antiretroviral therapy. On day 30, intensive PK sampling was performed after
      concurrent administration of NVP 200 mg and a single dose of EE/NET. RESULTS:
      Concomitant administration of NVP at steady state with EE/NET resulted in a
      significant (29%) median reduction in the area under the plasma concentration
      time curve (AUC(infinity)) and a significant reduction in mean residence time
      (MRT) and half-life (t(1/2)) of EE. There was a significant (18%) median
      reduction in the AUC(infinity) for NET that was not associated with a detectable
      change in NET C(max), MRT, or t(1/2). CONCLUSION: Oral contraceptives should not
      be the primary method of birth control in women of child-bearing potential who
      are treated with NVP.

PMID- 11981364
TI  - HIV seroincidence among patients at clinics for sexually transmitted diseases in
      nine cities in the United States.
AB  - Although the numbers of newly reported diagnoses of AIDS decreased in the 1990s,
      it is not clear whether they reflect a decreasing number of new HIV infections.
      Direct measurement of HIV incidence through follow-up cohort studies is difficult
      and costly. We estimated HIV incidence and trends in incidence among men who have
      sex with men (MSM) and heterosexual men and women at clinics for sexually
      transmitted diseases (STDs) by using a recently developed serologic testing
      algorithm that requires only a single blood specimen. Cross-sectional anonymous
      serosurveys were conducted at 13 STD clinics in nine cities in the United States
      from 1991 through 1997. Before anonymous HIV testing, demographic and clinical
      information was abstracted. Of 129,774 specimens tested, 362 (0.28%) were from
      persons estimated to be recently infected. Incidence among MSM was 7.1% (95%
      confidence interval (CI): 4.8-10.3), 14 times higher than that among
      heterosexuals, which was 0.5% (CI: 0.4- 0.7). Incidence among MSM and
      heterosexuals remained unchanged during the time studied. Decreasing rates of new
      AIDS diagnoses in the 1990s do not reflect stable rates of new HIV infections
      among MSM and heterosexual patients attending these clinics.

PMID- 11981365
TI  - Combination antiretroviral strategies for the treatment of pregnant HIV-1
      infected women and prevention of perinatal HIV-1 transmission.
AB  - CONTEXT: The Women and Infants Transmission Study is a prospective natural
      history study that has been enrolling HIV-1-infected pregnant women and their
      infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral
      regimens on perinatal HIV-1 transmission at the population level. DESIGN:
      Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542
      HIV-1-infected women with singleton live births between January 1990 and June
      2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1
      transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women
      who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for
      710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving
      dual antiretroviral therapy with no or one highly active drug (Multi-ART); and
      1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy
      (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for
      <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999;
      and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission
      increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral
      load. In multivariate analyses adjusting for maternal viral load, duration of
      therapy, and other factors, the odds ratio for transmission for women receiving
      Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95%
      CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of
      HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently
      associated with transmission. The protective effect of therapy increased with the
      complexity and duration of the regimen. HAART was associated with the lowest
      rates of transmission.

PMID- 11981366
TI  - Prevalence and correlates of highly active antiretroviral therapy switching in
      the Women's Interagency HIV Study.
AB  - OBJECTIVE: The purpose of this study was to describe the variability in highly
      active antiretroviral therapy (HAART) regimens over time, the extent to which
      individuals switch, and the characteristics of those who are switching. METHODS:
      We evaluated data collected between 1994 and 2000 from 1056 HIV-positive women
      enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating
      HAART. We described the variability and prevalence of changes in HAART regimens
      between semiannual visits, estimated time to switch using Kaplan-Meier methods,
      investigated factors associated with a first switch using Cox proportional
      hazards models, and compared disease markers among women switching or remaining
      on unchanged HAART regimens. RESULTS: We demonstrated a 13-fold increase in the
      number of unique HAART regimens reported since mid-1996 and showed that the
      amount of time spent on the first, second, or third regimen is similar, with an 8
      month median time to switching or discontinuing the initial HAART regimen. Women
      who switched had a lower mean CD4 cell count and were more likely to have HIV RNA
      levels greater than 400 copies/mL. Overall, the percentage of women switching
      decreased over the course of follow-up (to 37% in September 2000), although the
      percentage discontinuing therapy altogether increased 2-fold. CONCLUSION: Our
      findings on the relatively high rate of HAART switching emphasize the complexity
      of managing and evaluating these therapies.

PMID- 11981367
TI  - Evaluation of a non-name-based HIV reporting system in San Francisco.
AB  - OBJECTIVE: To develop and evaluate a non-name-based HIV reporting system.
      METHODS: A population-based study of the accuracy of a set of non-name codes and
      a prospective study of a laboratory-initiated HIV surveillance system conducted
      at a county hospital (site 1) and a health maintenance organization (site 2).
      Participants were persons reported with AIDS in San Francisco and patients with a
      positive test result for HIV antibody, p24 antigen, viral load, or a CD4 count at
      the study sites. RESULTS: Proper match rate was 95% for records with complete
      codes and records with at least 50% of the codes. Proper non-match rate was 99%
      for records with all code elements and 96% for records with at least 50% of the
      elements. Completeness of reporting was 89% (site 1) and 87% (site 2). Median
      number of days between test and receipt of test report at the health department
      was 9 days at site 1 and 7 days at site 2. During 1999, 78% of HIV-infected
      patients at site 1 and 87% at site 2 had an HIV-specific laboratory test.
      CONCLUSIONS: A non-name-based laboratory reporting system for HIV is feasible.

PMID- 11981368
TI  - HIV-1 and HIV-2 seroprevalence and risk factors among hospital outpatients in the
      Eastern Region of Ghana, West Africa.
AB  - A cross-sectional study of 854 outpatients seen at three hospitals in the Eastern
      Region of Ghana, West Africa assessed HIV-1 and HIV-2 seroprevalence rates and
      associated risk factors. During mid-1999, patients were tested in an anonymous
      study linked to a questionnaire and abstracted record data in three distinct
      communities with differing levels of urbanization. Combined HIV seroprevalence
      rates were 19.2% for Agomanya, the most rural community, 5.1% for Akwatia, and
      3.4% for Nkawkaw, the most urbanized community. HIV-1 infection alone accounted
      for 84.5% of cases, compared with 9.5% and 6.0% for HIV-2 and dual infection,
      respectively. In a multivariable model, the Agomanya location was significantly
      associated with HIV status (odds ratio [OR], 7.7; 95% confidence interval [CI],
      2.9-20.1; p <.0001). Employed people were also more likely to be infected (OR,
      4.3; 95% CI, 1.02-18.3; p =.047). Among prenatal patients, those from Agomanya
      were more likely to report no live-in partner or spouse compared with Nkawkaw and
      Akwatia (p <.0001). These findings suggest sexual partner exchange patterns may
      be more useful in explaining HIV seroprevalence rates than level of community
      urbanization. Intervention programs directed at these high risk populations for
      HIV infection in Ghana are urgently needed.

PMID- 11981369
TI  - Spectrum of commercial sex activity in Burkina Faso: classification model and
      risk of exposure to HIV.
AB  - OBJECTIVE: Before designing a sexually transmitted infection (STI)/HIV
      intervention study targeting female commercial sex workers in Bobo Dioulasso,
      Burkina Faso, we conducted a socioanthropologic survey to analyze the
      prostitution network in the city in 1998. According to social characteristics,
      women were classified in six different categories, including four groups of
      nonprofessional sex workers. The aim of the current study is to assess HIV
      exposure across this classification model. METHODS: A total of 447 women
      belonging to the six categories were enrolled in the study. After collection of
      social and behavioral data by means of a questionnaire, each woman received a
      physical examination and a blood sample was taken for HIV serologic testing.
      RESULTS: The category of "seaters" was the most often infected, with an HIV
      prevalence of 57% (58 of 101 women). Nonprofessional "sellers" and "bar
      waitresses" were more often infected than professional "roamers," with an HIV
      prevalence of 37% (24 of 65 women), 40% (27 of 67 women), and 29% (27 of 92
      women), respectively, despite a much lower number of clients per week (average of
      2.6 clients, 3.3 clients, and 18.6 clients, respectively). Finally, "students"
      and "cabarets" (women making and selling local beer in huts) were infected with
      an HIV prevalence of 15% (9 of 62 women and 9 of 60 women, respectively), which
      remains higher than the prevalence measured recently in the general female
      population in the city (6.4%). CONCLUSION: Our results highlight the high level
      of vulnerability of nonprofessional sex workers, who need to be considered in the
      design of any program targeting this population for STI/HIV control purposes.

PMID- 11981370
TI  - CRF06-cpx: a new circulating recombinant form of HIV-1 in West Africa involving
      subtypes A, G, K, and J.
AB  - Phylogenetic analysis of numerous strains of HIV-1 isolated from diverse
      geographic origins has revealed three distinct groups of HIV-1: groups M, N, and
      O. Within group M, subtypes, sub-subtypes and circulating recombinant forms
      (CRFs) exist. Recently, two near-full-length genomes of similar complex mosaic
      viruses containing fragments of subtypes A, G, I, and J were described in
      patients from Burkina Faso (BFP-90) and Mali (95ML-84). Here, we report on the
      characterization of two additional full-length genome sequences with similar
      mosaic structure in epidemiologically unlinked individuals from Senegal (97SE
      1078) and Mali (95ML-127). Phylogenetic and recombinant analysis confirmed that
      the previously described strains, BFP-90 and 95ML-84, were indeed a new CRF of
      HIV-1, which we can now designate as CRF06-cpx. This new CRF fits the complex
      (cpx) designation, because four different subtypes (A, G, K, and J) were involved
      in the mosaic genome structure. The fragment in the pol gene, which was initially
      characterized as unknown in the BFP-90 strain and subsequently as subtype I in
      the 95ML-84 strain, is now, with the recent description of the new K subtype,
      clearly identified as subtype K. CRF06-cpx circulates in Senegal, Mali, Burkina
      Faso, Ivory Coast, and Nigeria, although the exact prevalence remains to be
      determined. Importantly, this new variant has also been documented on other
      continents (Europe [France] and Australia), showing that these viruses are
      spreading not only locally but globally.

PMID- 11981371
TI  - High incidence of HIV-1 in South Africa using a standardized algorithm for recent
      HIV seroconversion.
AB  - Southern Africa has among the highest rates of HIV-1 infection in the world as
      judged by cross-sectional HIV-1 prevalence surveys carried out among women
      attending antenatal clinics. Incidence rates, which provide information on the
      number of new cases of infection, are more informative of the current state of
      the epidemic than estimates of prevalence, which provide information on the rates
      averaged over some previous time. Cohort studies to measure incidence rates are
      expensive and difficult to carry out, however, and few have been done in Africa.
      A recently developed standardized algorithm for recent HIV-1 seroconversion
      (STARHS) based on a sensitive/less-sensitive enzyme-linked immunosorbent assay
      was used to determine the incidence of HIV-1 subtype C infection among women
      attending public sector antenatal clinics in Hlabisa, a rural district in KwaZulu
      Natal, South Africa. The STAHRS results were confirmed by using a mathematic
      model to obtain an independent estimate of the age-specific incidence rates from
      the age-specific prevalence data. The data reveal extraordinarily high HIV-1
      incidence rates in South Africa. In 1999, the annual incidence of HIV-1 among
      susceptible women aged 15 to 49 years standardized to the age distribution of
      adult women in Hlabisa was 17%. Incidence peaked among 22-year-old women at 24%
      per year. The HIV-1 incidence rates provide valuable additional information
      indicating that new infections are continuing unabated and that the HIV-1
      epidemic is still growing in rural South Africa.

PMID- 11981372
TI  - Identification of a newly characterized HIV-1 BG intersubtype circulating
      recombinant form in Galicia, Spain, which exhibits a pseudotype-like virion
      structure.
AB  - We recently reported the finding of phylogenetically related HIV-1 BG
      intersubtype recombinant and G subtype nonrecombinant viruses circulating among
      injecting drug users in the region of Galicia in northwestern Spain. Here, we
      report the characterization of near full-length genome sequences of nine of these
      viruses (seven BG recombinant and two of nonrecombinant G subtype), obtained from
      epidemiologically unlinked individuals. Bootscan analysis reveals that six
      recombinant viruses share an identical mosaic structure, with two intersubtype
      breakpoints delimiting a B subtype segment comprising most of Env gp120 and the
      external portion of Env gp41, with the remaining portions of the genome being of
      subtype G, thus mimicking a pseudotype virion structure. The seventh BG
      recombinant virus exhibits breakpoints in env coincident with the other BG
      viruses but contains additional B subtype segments in gag and pol. In
      phylogenetic trees of complete genomes and of the B subtype segment of env, all
      seven BG viruses group in a monophyletic cluster. G subtype portions of the BG
      viruses group uniformly with the newly derived nonrecombinant G subtype viruses
      of Galicia in bootscan analysis, which points to the locally circulating G
      subtype strain as parental of the recombinants. These results allow us to define
      a new HIV-1 circulating recombinant form (CRF14_BG), the first reported to
      originate in Western Europe.

PMID- 11981373
TI  - Immune reconstitution after successful treatment with protease inhibitor-based
      and protease inhibitor-sparing antiretroviral regimens.

PMID- 11981374
TI  - Declining tuberculosis and drug resistance rate among HIV-positive patients at an
      Italian teaching hospital in the era of highly active antiretroviral therapy.

PMID- 11981375
TI  - Safety and tolerability of combination antiretroviral post-exposure prophylaxis
      in a population-based setting.

PMID- 11981376
TI  - Slangs have no place in this journal!

PMID- 11981378
TI  - Exostosis of the external auditory canal: a technical note.
AB  - OBJECTIVE: To describe the author's method of managing occlusive exostosis of the
      external auditory canal. STUDY DESIGN: Retrospective chart review. SETTING:
      Tertiary referral ambulatory otology clinic. PATIENTS: A case series of patients
      treated sequentially by the author over 15 years, all of whom had occlusive
      external auditory canal exostoses that could not be treated by medical
      management. INTERVENTION: Permeatal surgical removal of the anterior exostosis
      only. MAIN OUTCOME MEASURE: Surgical relief of occlusive external auditory canal
      disease by restoration of hearing and absence of infection with persistence of an
      external auditory canal and no symptoms of recurrence. RESULTS: A total of 8 men
      were treated by anterior exostosis removal. Follow-up continued on these patients
      for a period of 5 to 15 years after the operation, and none showed any evidence
      of recurrence or tendency to narrowing of the deep ear canal. One patient
      incurred a tympanic membrane perforation at escostosis surgery that was repaired
      during the operation. CONCLUSION: Anterior exostosis removal by a permeatal route
      is a safe, rapid, and effective method of relieving patients of occlusive
      external auditory canal exostosis. By leaving the posterior exostosis intact,
      patients are not put at risk for injury to the facial nerve, chorda tympani
      nerve, or ossicles. When the deep ear canal is drilled blind, there are no
      landmarks to indicate the true path of the external canal.

PMID- 11981379
TI  - Total middle ear reconstructive surgery for the radicalized ear.
AB  - OBJECTIVE: To evaluate the efficacy of total middle ear reconstructive surgery
      (TMRS) for patients with open cavity problems. STUDY DESIGN: Retrospective study
      of patients treated between 1994 and 1997. SETTING: Tertiary care, referral
      medical center. PATIENTS: Fifty-nine consecutive patients (62 ears) with open
      cavity problems (draining ears) who underwent TMRS. MAIN OUTCOME MEASURES:
      Postoperative states of the ears and complications were evaluated in two groups,
      with and without persistent purulent otorrhea at the time of surgery. RESULTS: In
      the noninfected group, ears without otorrhea were maintained in 12 (100%) of 12
      ears in the short term and 10 (83%) of 12 ears in the long term. In the infected
      group, the proportions were 40 (80%) of 50 ears and 35 (73%) of 48 ears, for the
      short and long terms, respectively. Hollowing and/or retraction of the
      reconstructed canal wall was observed in 1 (8%) of 12 ears of the noninfected
      group and in 15 (31%) of 48 ears of the infected group after long-term follow-up.
      Postoperative complications were encountered in 9 ears (14.5%) in the infected
      group only. CONCLUSIONS: Total middle ear reconstructive surgery is considered
      useful for the management of persistent discharge from radicalized cavities. It
      was found important to minimize infection at the time of surgery to achieve
      satisfactory results.

PMID- 11981380
TI  - Expression of bone morphogenetic protein-2 messenger ribonucleic acid in
      cholesteatoma fibroblasts.
AB  - HYPOTHESIS: The aim of the study was to evaluate the role of bone morphogenetic
      protein-2 (BMP-2) in the pathology of middle ear cholesteatoma. BACKGROUND:
      Middle ear cholesteatoma is a chronic inflammatory disease associated with
      destruction of the temporal bone and marked by increased expression levels of
      diverse cytokines. Bone remodeling associated with this disease is mainly caused
      by the action of osteoclasts. It has been shown that BMP-2 expression is
      inducible by interleukin 1 in synovial fibroblasts and that BMP-2 in combination
      with interleukin 1alpha is able to stimulate the formation of osteoclast-like
      multinucleated cells in co-cultures of osteoblast-like cells and hematopoietic
      cells. METHODS: By using Northern hybridizations, we examined the messenger
      ribonucleic acid expression of BMP-2 in keratinocytes and fibroblasts derived
      from normal external ear canal skin (EACS) and from cholesteatoma, respectively.
      RESULTS: We show that normal EACS fibroblasts do not express BMP-2, whereas
      keratinocytes of both EACS and cholesteatoma origin are positive for the BMP-2
      transcript. In contrast to EACS fibroblasts, BMP-2 is clearly expressed in
      cholesteatoma perimatrix fibroblasts. Incubation of normal fibroblasts with
      cholesteatoma extracts caused the transcription of BMP-2. Interleukin 1alpha,
      bacterial endotoxin, or bovine keratin, however, were not able to initiate BMP-2
      expression in normal fibroblasts. CONCLUSION: In view of the above data, it is
      tempting to speculate that BMP-2 expression might play a role in cholesteatoma
      pathology.

PMID- 11981381
TI  - Three-dimensional modeling of middle ear biomechanics and its applications.
AB  - HYPOTHESIS: This study investigated whether combined technologies of finite
      element (FE) analysis and three-dimensional reconstruction of human temporal
      bones could be used to construct a computational model, useful in describing
      normal and pathologic middle ear sound conduction. BACKGROUND: FE models for
      biologic systems have been used in ear biomechanics. Three-dimensional
      reconstructions have also been made, but not in combination with FE modeling and
      laser interferometry measuring of human temporal bones. Furthermore, an FE model
      for the human middle ear with its ossicular attachments has not been reported on
      the basis of temporal bone histologic sections and morphometric reconstruction,
      to the authors' best knowledge. Because of the size, variability, and complexity
      of the middle ear, accurate morphologic data and boundary conditions are
      necessary for accurate FE modeling. METHODS: A fresh temporal bone was
      decalcified, embedded in celloidin, sectioned and stained, scanned, and
      digitized, and the normal middle ear was reconstructed. The histologic sections
      were used to construct a computer-aided design model with ligaments, muscles, and
      tendons as boundary conditions. The data thus obtained were converted into an FE
      mechanical model that was validated by comparison with displacements obtained by
      laser Doppler interferometry on 17 fresh human temporal bones. RESULTS: An FE
      model was generated, demonstrating dynamic behavior that moderately approximated
      the laser interferometric data from human temporal bones receiving 90-dB sound
      pressure level auditory frequencies at the tympanic membrane. CONCLUSION:
      Accurate FE modeling, incorporating both morphometric and interferometric
      performance data, predicted both normal and pathologic mechanical performance of
      the human ossicular chain.

PMID- 11981382
TI  - Causes of conductive hearing loss after stapedectomy or stapedotomy: a
      prospective study of 279 consecutive surgical revisions.
AB  - OBJECTIVE: To analyze the causes for residual or recurrent conductive hearing
      loss following stapedectomy or stapedotomy and then propose surgical techniques
      to avoid these complications. STUDY DESIGN: Prospective study of 279 consecutive
      stapedectomy or stapedotomy revisions performed by the author. SETTING: Tertiary
      referral center. PATIENTS: The study included 260 patients who presented with a
      20 dB or greater average air-bone gap in the speech frequencies 1 month to 35
      years following stapedectomy or stapedotomy (19 patients were explored for
      possible oval window perilymph fistula). INTERVENTION: Stapedectomy (stapedotomy)
      surgical revision. MAIN OUTCOME MEASURES: Microscopic inspection and palpation
      assessed the mobility and continuity of the malleus, incus, and prosthesis.
      Infrared laser vaporization thinned the oval window neomembrane to identify the
      precise depth and margins of the oval window, the presence of residual stapes
      footplate, and finally, the relationship of the prosthesis to the fenestra into
      the vestibule. RESULTS: Prosthesis displacement out of the oval window
      fenestration with fixation of the prosthesis against the residual stapes
      footplate or otic capsule margin was demonstrated in 81% (211/260) of the
      patients. Of these patients, 31% had complete incus erosion, and an additional
      60% demonstrated partial incus erosion, usually on the undersurface of the incus.
      Residual fixed stapes footplate was found in 14%, and malleus fixation in 4%.
      Incus dislocation was found in 4%, and incus fixation in 2%. CONCLUSIONS:
      Prosthesis migration and subsequent fixation caused the majority of stapedectomy
      failures. Collagen contracture of the oval window neomembrane lifts the
      prosthesis out of the oval window fenestration. Prosthesis displacement then
      results from adhesions pulling the prosthesis or mechanical forces further
      tilting the prosthesis. Incus erosion results from vibration against the fixed
      prosthesis. Six specific stapedotomy recommendations are made to minimize
      postoperative prosthesis migration.

PMID- 11981383
TI  - Stapes surgery: how precisely do different prostheses attach to the long process
      of the incus with different instruments and different surgeons?
AB  - HYPOTHESIS: The goal of this study was to compare the attachment of stapes
      prostheses with differently shaped loops to the long process of the incus.
      BACKGROUND: In stapes surgery, the attachment of the prosthesis to the long
      process of the incus plays an important role concerning the gain in hearing and
      the development of late complications such as incus erosion and necrosis. Band
      shaped and spiral loops have been developed to achieve a broad, firm attachment
      to the long process of the incus. During stapes surgery, the view at the
      prosthesis is restricted, making it impossible to evaluate the effects of the
      differently shaped loops. METHODS: Gold, steel/Teflon, platinum/Teflon, and two
      different titanium stapes prostheses were inserted in 30 specially prepared
      temporal bones by three experienced surgeons using the Fisch technique with the
      McGee and straight alligator forceps for the crimping of the loops. Photographs
      were taken with 0- and 70-degree rod lens telescopes at defined views. RESULTS:
      In all prostheses, a sufficiently firm attachment to the long process of the
      incus was achieved. The attachment of band-shaped loops proved to be better with
      the straight alligator forceps. The band-shaped loops showed a better contact
      with the incus than did the wire loops. However, the broad spiral-shaped loops
      led to a loss of the perpendicular axis of the piston to the long incus process.
      CONCLUSION: The geometry of the loop affects the final length of the piston in
      the vestibule and its angle to the long process of the incus.

PMID- 11981384
TI  - Transmeatal low-power laser irradiation for tinnitus.
AB  - OBJECTIVE: To evaluate effectiveness of 60-mW laser irradiation in the treatment
      of tinnitus. STUDY DESIGN: Prospective, randomized double-blind study. METHODS:
      This investigation included 68 ears in 45 patients with disabling unilateral or
      bilateral tinnitus. The active or placebo laser treatment was administered
      transmeatally once a week for 6 minutes. Laser irradiation was performed four
      times during a 4-week period. A questionnaire was administered to evaluate the
      loudness, duration, quality, and annoyance of tinnitus before and after
      irradiation. The loudness and pitch match for tinnitus were obtained, and
      distortion product otoacoustic emissions were also examined. RESULTS: No
      significant difference was observed between the active and placebo laser groups
      with regard to outcome of loudness, duration, quality, and annoyance of tinnitus.
      In one patient who received active laser treatment, acute hearing deterioration
      occurred after the third irradiation. CONCLUSION: Transmeatal low-power laser
      irradiation with 60 mW is not effective for the treatment of tinnitus.

PMID- 11981385
TI  - Treatment of sudden sensorineural hearing loss with systemic steroids and
      valacyclovir.
AB  - OBJECTIVE: To determine if the addition of an antiviral medication to systemic
      steroids improves recovery in the treatment of idiopathic sudden sensorineural
      hearing loss. STUDY DESIGN: Randomized, double-blind, placebo-controlled
      prospective multicenter clinical trial. SETTING: The study was administrated from
      a tertiary care center and clinical research institute; patients were enrolled by
      otolaryngologists in academic and private practice outpatient settings. PATIENTS:
      Inclusion criteria included 1) loss of at least 30 dB in 3 contiguous frequencies
      over <3 days in patients with previous audiometry, 2) marked loss of hearing in
      patients with prior subjectively normal hearing and no previous audiometry, with
      contralateral hearing taken as baseline, and 3) patients seen within 10 days of
      onset of hearing loss. Pretreatment evaluation included audiometry and complete
      blood cell count, complete blood chemistry, and fluorescent treponemal antibody
      absorption test. Auditory brainstem-evoked response or magnetic resonance imaging
      was recommended. INTERVENTION: Patients received prednisone (80 mg/d for 4 d,
      then tapered over 8 d) with placebo or prednisone with valacyclovir (1 g, 3 times
      a day for 10 days). MAIN OUTCOME MEASURE: 1) Audiometric assessment at
      presentation, Week 2, and Week 6; 2) Hearing Screening Inventory questionnaire
      twice weekly for 6 weeks; and 3) acute Short Form-12 questionnaire at
      presentation and Week 2. RESULTS: Of 105 subjects enrolled in the study, 84
      subjects were evaluable. There were no significant differences between placebo
      and valacyclovir treatment groups in terms of hearing recovery or symptom
      recovery on the basis of the Hearing Screening Inventory or Short Form-12
      questionnaires. No adverse events were related to the use of valacyclovir.
      CONCLUSION: Within the paradigm used in the current study, an antiviral
      medication did not provide more benefit than steroid alone in the treatment of
      idiopathic sudden sensorineural hearing loss.

PMID- 11981386
TI  - Hyperfibrinogenemia as a risk factor for sudden hearing loss.
AB  - OBJECTIVE: To clarify predisposing conditions for vascular events. SETTING:
      Vascular events, immunologic processes, and viral infections have to be
      considered as pathomechanisms for most cases of sudden hearing loss. STUDY
      DESIGN: Hemorrheologic parameters were studied in 53 patients with sudden hearing
      loss within 5 days of the onset. PATIENTS: A control group of 53 normal-hearing
      people was matched pairwise according to age and gender. RESULTS: Fibrinogen
      levels were significantly higher in patients with sudden hearing loss (343 +/- 98
      mg/dl) than in control subjects (303 +/- 69 mg/dl). Erythrocyte aggregation (27.3
      +/- 5.6 a.u. versus 20.9 +/- 8.5 a.u.) and plasma viscosity (1.31 +/- 0.13 mPa/s
      versus 1.26 +/- 0.08 mPa/s) in patients with SHL were also significantly higher
      than in control subjects. No significant difference could be found in the
      parameters of clinical chemistry, hematology, and hemostasias investigated.
      CONCLUSION: Because elevated plasma fibrinogen plays a major role in
      cardiovascular diseases such as myocardial infarction and stroke, it is possible
      that this plasma protein is also involved in the pathogenesis of sudden hearing
      loss of vascular origin. More research is still required to determine the value
      of measuring plasma fibrinogen levels in clinical practice and identifying
      hyperfibrinogenemia in sudden hearing loss.

PMID- 11981387
TI  - Dynamics of sensorineural hearing loss after head trauma.
AB  - OBJECTIVE: To estimate the temporal endpoint of permanent sensorineural hearing
      loss after head trauma. STUDY DESIGN: Retrospective observational case study.
      PATIENTS: In patients with sensorineural hearing loss caused by head trauma,
      1,741 ears were studied. MAIN OUTCOME MEASURE: A follow-up survey of audiograms
      in patients with sensorineural hearing loss after head trauma was performed for
      up to 4 years from the date of injury. Each patient's audiograms were compared
      according to a severity score that specifically classified hearing loss that was
      associated with acoustic trauma. RESULTS: Either improvement or deterioration of
      the early posttrauma hearing loss occurred during the first year after head
      trauma. Thereafter, hearing levels could be expected to remain stationary.
      CONCLUSION: Fluctuation in hearing after head trauma may take place within the
      first year after trauma, after which the associated hearing loss should be
      considered to be stabilized.

PMID- 11981388
TI  - Clinical implications of inflammatory cytokines in the cochlea: a technical note.
AB  - HYPOTHESIS: Establishing the presence of critical cellular stress response
      components in cochlear cells can contribute to a better understanding of cochlear
      cell biology and pathology. BACKGROUND: Inflammatory cytokines and related
      proteins play critical roles in a variety of cellular processes, but to date,
      little is known about the identity and cellular localization of these compounds
      within the ear. Cytokines are autocrine, which means that cells that produce them
      have corresponding surface receptors. The presence of these receptors makes the
      cells vulnerable to disruption by circulating or local sources of cytokines and
      related ligands. Such disruptions may explain previously poorly understood
      cochlear pathologies. METHODS: The messenger RNA precursors that encode
      inflammatory cytokines and related proteins are identified in the inner ear by
      using reverse transcriptase-polymerase chain reaction. Cochlear cells that
      contain the corresponding proteins are identified by immunostaining. RESULTS:
      Messenger RNA for interleukin-1alpha, tumor necrosis factor alpha, NFkappaB P65
      and P50, and IkappaBalpha was found in cochlear tissue. Cells that immunostained
      most conspicuously for cytokine production are Type I fibrocytes and root cells
      located within the spiral ligament. CONCLUSION: Production of inflammatory
      cytokines by the above-mentioned cells indicates that they are vulnerable to
      disruption by extra-cochlear sources of cytokines and associated ligands. These
      cells play critical roles in cochlear function, and their disruption could induce
      hearing loss. These findings suggest that systemic or local production of
      inflammatory ligands may play roles in a number of causes of deafness, including
      immune mediated hearing loss, sudden hearing loss, and sensorineural hearing loss
      associated with otosclerosis, otitis media, and bacterial meningitis.

PMID- 11981389
TI  - Changes in quality of life and the cost-utility associated with cochlear
      implantation in patients with large vestibular aqueduct syndrome.
AB  - OBJECTIVE: A group of 20 patients with large vestibular aqueduct syndrome was
      identified at the Indiana University School of Medicine. The major objective of
      this study was to explore the improvements in quality of life associated with
      cochlear implantation in patients with large vestibular aqueduct syndrome, as
      well as the cost-utility of cochlear implantation in this group. SETTING: A total
      of 70 patients were identified with large vestibular aqueduct syndrome through
      analysis of thin-section computed tomography of the temporal bone over the past 6
      years at this medical center. Data collected from the medical records for each
      patient included demographic data, hearing-related statistics, implantation data,
      and audiometric data. Sixteen children and adults with large vestibular aqueduct
      syndrome had undergone cochlear implantation before the beginning of this study,
      and the remaining 54 children and adults were identified as undergoing treatment
      of progressive or fluctuant sensorineural hearing loss. Health utility indexes
      used in this analysis were taken through the use of the Ontario Health Utility
      Index, Mark III. The range of costs used for cost-utility analysis was derived
      from the costs of cochlear implantation at this medical center, as well as from
      costs associated with implantation published in the medical literature. METHODS:
      Participants were selected from the total population of patients with large
      vestibular aqueduct syndrome at this center who were postlingually deafened and
      who currently had severe hearing loss. Two groups were formed. These groups
      comprised either cochlear implant patients with large vestibular aqueduct
      syndrome or patients with large vestibular aqueduct syndrome currently using
      hearing aids. Ten of the 16 cochlear implant patients and 10 of the remaining 54
      patients with large vestibular aqueduct syndrome met these criteria. Mark III
      health utility indexes were distributed to patients in each group and scored.
      Those health utility indexes not completed by the patients were scored by proxy,
      using the audiologist at this center who was the most familiar with the patient.
      Changes in quality of life associated with cochlear implantation were derived by
      comparison of the health utility index results of the two groups. Cost-utility
      measures were then made using discounted costs per quality-of-life years (QALYs)
      (5%), and a sensitivity analysis was performed that evaluated changes in scoring
      done by proxy. The cost-utility results were then compared with the cost
      utilities derived from similar studies and associated with other disease states.
      RESULTS: Although both groups of patients had significant hearing loss, the
      hearing aid group had a better mean pure-tone average. The mean pure-tone average
      for the hearing aid group was 70.8 dB (SD 24.4), and the mean pure-tone average
      for the cochlear implant group was 107.0 dB (SD 21.7). Seven of the 20 health
      utility indexes were scored by proxy. Results from the base case indicate a 0.20
      gain in health utility from cochlear implantation (hearing aid = 0.62, cochlear
      implant = 0.82, p = 0.037), resulting in a discounted cost per QALY of $12,774.
      Sensitivity analysis of the proxy scoring indicated that decreasing the hearing
      score one level on the health utility index resulted in a gain in health utility
      with cochlear implantation of 0.15, resulting in a discounted cost per QALY of
      $17,832. A decrease of the hearing score by two levels on the health utility
      survey resulted in no significant gain in quality of life with cochlear
      implantation. CONCLUSION: This study found an improvement in quality of life
      associated with cochlear implantation in postlingually deafened patients with
      large vestibular aqueduct syndrome. By weighing this improvement in quality of
      life against the significant difference noted between the pure-tone averages of
      each group, further strength can be given to this conclusion. This gain in
      quality of life, as well as the results derived for the cost-utility of cochlear
      implantation, was similar to that in previous published studies of cochlear
      implantation in all types of patients. These results also indicate a favorable
      cost-utility when compared with published data about other disease states. As
      patients with large vestibular aqueduct syndrome progress to profound levels of
      hearing loss, these results indicate that cochlear implantation can be offered as
      a beneficial, life-improving therapy.

PMID- 11981390
TI  - Outcome of cochlear implantation in pediatric auditory neuropathy.
AB  - OBJECTIVE: Auditory neuropathy, characterized by absence or abnormality of
      auditory brainstem responses and normal otoacoustic emissions, is often
      associated with particularly poor response to amplification. Outcome data from
      four such pediatric patients who received cochlear implants are discussed. STUDY
      DESIGN: Four patients from the Carolina Children's Communicative Disorders
      Program were identified as having received a diagnosis of auditory neuropathy
      before implantation with a Clarion cochlear implant. Speech data collected after
      implantation were compared with data from control pediatric implant patients,
      matched for age at implantation and duration of implant use. Electrically evoked
      auditory brainstem response data and electrically evoked acoustic reflex data
      were also obtained. METHODS: Routine clinical procedures were used to obtain
      speech outcome data. A 75-micros biphasic 21.1-Hz pulse train served as the
      eliciting stimulus for both evoked auditory brainstem responses and reflex
      measures, which were obtained contralateral to the implant. RESULTS: Speech data
      were comparable with those obtained from the general population of pediatric
      patients receiving cochlear implants at this center. Identifiable evoked auditory
      brainstem response data were obtained in all subjects on at least two of the
      three electrodes tested, and variability was comparable with that observed in
      other children with implants. A robust electrically evoked acoustic reflex with
      no decay was observed at estimated M-level in all children. CONCLUSION: The data
      gathered to date suggest that the outcome of cochlear implantation in these four
      patients is not significantly different from that in other pediatric implant
      patients. Physiologic data suggest that the implant was able to overcome the
      desynchronization hypothesized to underlie auditory neuropathy.

PMID- 11981391
TI  - Delayed implantation in congenitally deaf children and adults.
AB  - OBJECTIVE: To determine the efficacy of cochlear implants with current processing
      strategies in children and adults with long-term congenital deafness, and to
      determine whether the growth of auditory perceptual skills in these patients is
      similar to the data reported for patients who have undergone implantation with
      earlier devices and coding strategies. STUDY DESIGN: A prospective study of
      children and adults fulfilling the study inclusion criteria. SETTING: University
      medical center. PATIENTS: Thirty-five congenitally deaf children who received
      implants after the age of 8 years and 14 congenitally deaf adults who received
      implants as adults participated in this study. Length of device use ranged from 6
      months to 3 years. MAIN OUTCOME MEASURES: Open set phoneme, word recognition
      tests, and sentence recognition tests were administered in quiet and noise
      auditory only conditions preoperatively and postoperatively. Changes in test
      scores were examined by paired t tests, and differences between groups were
      compared by Student's t tests. Spearman correlation coefficients were calculated
      to identify associations between scores and subject characteristics. A two-sided
      alpha of less than 0.05 was considered statistically significant. RESULTS: The
      results indicated significant improvement in open set speech perception skills in
      the children after implantation; the adults demonstrated improved mean scores on
      both word and sentence recognition. A shorter length of deafness correlated with
      better postoperative performance, but all subjects continued to improve over
      time. The improvement in test scores was similar between the devices, and no
      significant differences were detected between the different processing
      strategies. CONCLUSION: Children and adults with long-term congenital deafness
      can obtain considerable open set speech understanding after implantation. Length
      of deafness (age at implantation), length of device use, and mode of
      communication contribute to outcome.

PMID- 11981392
TI  - Nucleus multichannel cochlear implantation in partially ossified cochleas using
      the Steenerson procedure.
AB  - OBJECTIVE: The purpose of this study was to report hearing results obtained in a
      group of subjects who received scala vestibuli implantation because of cochlear
      ossification and to compare these results to those in patients with scala tympani
      implantation. STUDY DESIGN: Retrospective analysis of consecutive cochlear
      implant procedures. SETTING: Department of Otolaryngology, University of Parma.
      PATIENTS: Five postlingually deafened adults with an electrode array placed into
      the scala vestibuli were compared with the speech performance of matched controls
      who had the electrode array inserted into the scala tympani. MAIN OUTCOME
      MEASURES: Measures included vowel and consonant speech identification scores,
      bisyllabic word and sentence speech recognition scores, and common phrases
      comprehension scores. RESULTS: No significant difference was detected on speech
      performances between the subjects with scala vestibuli implantation and the
      control group. CONCLUSION: Scala vestibuli implantation appears to be an
      excellent alternative in cases in which scala tympani is found to be not patent.

PMID- 11981393
TI  - Three familial cases of Michel's aplasia.
AB  - Complete agenesis of the bony labyrinth, first described by Michel, represents
      the most severe form of inner ear defect. A search of the literature yielded only
      one report of this rare anomaly, affecting two siblings. Three familial cases of
      bilateral inner ear aplasia are reported here, and the probable inheritance
      pattern of this condition is discussed.

PMID- 11981394
TI  - Nasopharyngeal penicillin-resistant Streptococcus pneumoniae strains among young
      children in Japan.
AB  - OBJECTIVE: A rapid increase of penicillin resistance in Streptococcus pneumoniae
      has recently been reported in most areas of the world. Penicillin-resistant S.
      pneumoniae and other resistant bacteria are the principal causes of recurrent
      acute otitis media (AOM). Penicillin-resistant S. pneumoniae was examined so that
      we could investigate the bacteriologic and clinical interpretations of
      nasopharyngeal flora from healthy children. METHODS: We obtained nasopharyngeal
      swab specimens from healthy children attending a day care center and from
      children attending a public health examination in Kanazawa, Japan. We also
      obtained clinical specimens from children with AOM who visited the Kanazawa
      University Hospital and 4 other hospitals in Ishikawa Prefecture in Japan.
      RESULTS: The chief bacteria from the children were S. pneumoniae, Haemophilus
      influenzae, and Moraxella catarrhalis. Penicillin-resistant S. pneumoniae was
      identified in 75% of children attending a day care center. On the other hand, S.
      pneumoniae was identified in 37% of children who were not attending day care. Of
      the children with AOM, penicillin-resistant S. pneumoniae was identified in 77%.
      CONCLUSION: Our results suggest that there is a strong relationship between day
      care attendance and nasopharyngeal carriage of S. pneumoniae. The carriage rate
      of penicillin-resistant S. pneumoniae in healthy children in day care centers was
      very high and similar to the carriage rate of young patients with AOM in Japan.

PMID- 11981395
TI  - Late-onset, progressive sensorineural hearing loss after severe neonatal
      respiratory failure.
AB  - OBJECTIVES: To determine the prevalence of sensorineural hearing loss (SNHL) at
      the age of 4 years among survivors of severe neonatal respiratory failure with
      and without congenital diaphragmatic hernia and to document the occurrence of
      late-onset or progressive SNHL among the survivors. DESIGN: Prospective,
      longitudinal secondary outcome study. SETTING: Multicenter Canadian study in 9
      tertiary referral centers. PATIENTS: Eighty-one (89%) of ninety 4-year-old
      survivors born from 1994 to 1996 of > or =34 weeks gestation at birth with severe
      neonatal respiratory failure (2 oxygenation indices > or =25 at least 15 minutes
      apart). MAIN OUTCOME MEASURES: Repeated audiologic measurements from birth to the
      age of 4 years with documentation of the entire cohort at 2 and 4 years of age.
      RESULTS: Forty-three (53%) of 81 tested 4-year-old survivors had SNHL; 28 (42%)
      of 66 without congenital diaphragmatic hernia and 15 (100%) of 15 with congenital
      diaphragmatic hernia. High-frequency SNHL occurred in 65% of the patients. Of the
      43 children with SNHL at 4 years, 30 (70%) had loss at 2 years, and 18 (60%) of
      these 30 had progressive loss between 2 and 4 years of age. For 13 children with
      SNHL onset after 2 years of age, the loss was less severe with lesser involvement
      of the lower frequencies. CONCLUSION: Survivors of severe neonatal respiratory
      failure frequently develop late-onset SNHL that may be progressive. Urgent
      investigation is required to enable further understanding and prevention of this
      problem. Severe neonatal respiratory failure should be an indication for long
      term audiologic surveillance.

PMID- 11981396
TI  - New approaches to the management of peripheral vertigo: efficacy and safety of
      two calcium antagonists in a 12-week, multinational, double-blind study.
AB  - OBJECTIVE: To evaluate the efficacy and safety profile of one 30-mg nimodipine
      oral tablet taken three times per day (one tablet with breakfast, one with lunch,
      and one with dinner) or one 150-mg cinnarizine verum oral capsule taken once each
      day with dinner for 12 weeks. STUDY DESIGN: Comparative in a double-blind,
      multinational pilot study. SETTING: Tertiary referral center. PATIENTS: A total
      of 221 patients met the study criteria; of that total, 181 adult patients
      completed the study, including 135 women and 46 men whose ages ranged from 20 to
      80 years. INTERVENTIONS: Two calcium antagonists were used to treat vertigo
      (nimodipine, 89 patients; cinnarizine, 92 patients), and all patients were
      maintained on the same dosage regimen until they completed 12 weeks of treatment.
      Patients were evaluated at 2-and 4-week intervals; an additional evaluation was
      made at Week 14 to determine vertigo recurrence in the posttreatment period. MAIN
      OUTCOME MEASURES: The response was evaluated by using the vertigo severity index,
      a count of vertigo episodes in a given time period. Each episode is weighted
      according to its intensity. RESULTS: Nimodipine treatment decreased the incidence
      of moderate vertigo episodes by 78.8% and decreased severe vertigo episodes by
      85.0%. Cinnarizine treatment decreased the incidence of moderate vertigo episodes
      by 65.8% and decreased severe vertigo episodes by 89.8%. Nimodipine and
      cinnarizine exhibited similar safety profiles. Only two patients withdrew from
      the study because of adverse events possibly related to the study drug. One
      patient withdrew from the cinnarizine group because of headache, and one patient
      withdrew from the nimodipine group because of lipothymia. CONCLUSION: These data
      confirm the marked efficacy of both nimodipine and cinnarizine in the treatment
      of vestibular vertigo.

PMID- 11981397
TI  - Migraine-associated dizziness: patient characteristics and management options.
AB  - OBJECTIVE: To determine patient characteristics and effectiveness of therapy for
      migraine-associated dizziness. STUDY DESIGN: Retrospective chart review. SETTING:
      Tertiary referral center. PATIENTS: Patients were identified through a code query
      of billing records for the diagnosis of migraine-associated vertigo or
      disequilibrium, based on the International Headache Society criteria. There were
      81 patients (61 women, 20 men) with an average age of 36.6 years (range, 8-71
      yr); all except four patients were evaluated between 1995 and 1999. Follow-up was
      obtained from chart review. Mean follow-up time was 54.5 weeks, with a range of 4
      to 456 weeks. INTERVENTION: One or more treatment methods, including dietary
      manipulation, medication (tricyclic antidepressants, beta-blockers or calcium
      channel blockers), and neurology consultation, were applied sequentially as
      necessary. MAIN OUTCOME MEASURE: Response to therapy was defined as greater than
      75% reduction in symptom recurrence rate. RESULTS: Overall, 72% of patients
      experienced resolution or dramatic reduction of their attacks of vertigo or
      disequilibrium. Of the 13 patients treated with the introduction of dietary
      manipulation alone, 100% received significant relief. Of the 31 patients treated
      with dietary manipulation and the addition of a medication, 77% of these patients
      had significant relief. Of the final group of 37 patients treated with another
      medication or a neurology consultation, 57% received substantial relief. Of the
      responders, the majority (>95%) experienced an equal reduction in both vertigo or
      disequilibrium and headache symptoms. Interestingly, 100% of the patients in the
      migraine without active headache group received substantial relief of their
      vertigo or disequilibrium symptoms with migraine therapy. CONCLUSION: We conclude
      that there is effective therapy for the common problem of migraine-associated
      dizziness.

PMID- 11981398
TI  - Vertical dynamic visual acuity in normal subjects and patients with vestibular
      hypofunction.
AB  - OBJECTIVE: This study was designed to measure visual acuity during active
      vertical head movement and to examine its relationship to subjective reports of
      oscillopsia. STUDY DESIGN: This was a prospective, clinical study. SETTING: The
      study was performed in a tertiary, ambulatory referral center. PATIENTS: Thirty
      normal subjects, 13 patients with unilateral vestibular hypofunction, 11 patients
      with bilateral vestibular loss, and 10 patients with nonvestibular dizziness were
      examined. Vestibular loss was confirmed with caloric or rotary chair testing.
      INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Reliability, sensitivity, and
      specificity of a computerized test that measures visual acuity during active
      vertical head movement. Subjective complaint of oscillopsia was measured by use
      of a visual analog scale. RESULTS: The active vertical head movement test was
      reliable both for normal subjects (intraclass correlation coefficient, r = 0.89)
      and for patients with dizziness (intraclass correlation coefficient, r = 0.94).
      Age contributed significantly to active vertical head movement in normal subjects
      and in patients with dizziness over the age of 46 years but not in younger
      subjects. Older subjects had a decrement in active vertical head movement
      compared with younger subjects. Subjective reports of oscillopsia did not
      correlate positively with active vertical head movement. CONCLUSION: The active
      vertical head movement test is a reliable measure of visual acuity during active
      vertical head motion. The effect of age on active vertical head movement may
      reflect the physiologic impact of neuronal loss with aging. The poor correlation
      between active vertical head movement and reports of oscillopsia may be caused by
      the predictability of head movements during the active vertical head movement
      test compared with the unpredictability of head movements during walking.

PMID- 11981399
TI  - Hearing preservation surgery for small endolymphatic sac tumors in patients with
      von Hippel-Lindau syndrome.
AB  - OBJECTIVE: To determine the incidence of bilateral endolymphatic sac tumors in
      von Hippel-Lindau syndrome and to describe the technique and results of hearing
      preservation surgery for small endolymphatic sac tumors in a series of patients
      with von Hippel-Lindau syndrome. STUDY DESIGN: Analysis of the literature to
      determine the incidence of bilateral endolymphatic sac tumors and a retrospective
      case review of hearing preservation surgery for removal of small endolymphatic
      sac tumors in four patients with von Hippel-Lindau syndrome. SETTING: Tertiary
      care academic medical centers. PATIENTS: Four patients with von Hippel-Lindau
      syndrome (three with bilateral endolymphatic sac tumors) and progressive
      sensorineural hearing loss in which preoperative imaging studies revealed in situ
      or small endolymphatic sac tumors without ipsilateral labyrinthine destruction.
      INTERVENTION: All four patients had complete surgical excisions of the
      endolymphatic sac tumor via one of three surgical approaches with the goal of
      hearing preservation. One patient had bilateral surgery. MAIN OUTCOME MEASURES:
      Audiometric and radiographic. RESULTS: Nearly one-third (30.2%) of patients with
      von Hippel-Lindau syndrome and endolymphatic sac tumors have bilateral disease.
      All four patients (five ears) maintained serviceable hearing postoperatively
      after surgical excision of the endolymphatic sac tumor via a variety of approach
      options. CONCLUSION: The discovery of a small or in situ endolymphatic sac tumor
      affords the patient the option of surgical removal with hearing preservation.
      This is critical in the patient with von Hippel-Lindau syndrome who is at risk
      for bilateral disease and complete bilateral anacusis if tumor growth progresses.

PMID- 11981400
TI  - Predictive factors of long-term facial nerve function after vestibular schwannoma
      surgery.
AB  - OBJECTIVE: To assess predictive factors of long-term facial nerve function in a
      series of patients undergoing vestibular schwannoma surgery and to evaluate the
      reproducibility of the relevant parameters. STUDY DESIGN: Prospective. SETTING:
      Three tertiary referral neurotology units in two separate countries. PATIENTS: A
      total of 67 patients, with normal preoperative facial function and an
      anatomically intact facial nerve postoperatively, undergoing vestibular
      schwannoma surgery during a sequential 18-month period. INTERVENTIONS: Recording
      of intraoperative stimulus amplitudes (minimum intensity medial to the tumor
      after excision) and postoperative facial nerve function up to 2 years after
      surgery. MAIN OUTCOME MEASURES: Long-term facial nerve function related to tumor
      size, early postoperative facial nerve function, and intraoperative
      electrophysiologic intensities. RESULTS: Multivariate logistic regression model
      identified tumor size and the minimum intensity required to provoke a stimulus
      threshold event medial to the tumor after excision as independent predictors of a
      favorable initial outcome. Immediate facial nerve function was the only
      independent predictor of long-term normal function. The sensitivity of this
      predictor was 95% (95% confidence interval [CI], 89-100%); specificity, 83% (95%
      CI, 62-100%); positive predictive accuracy, 96% (95% CI, 91-100%); and negative
      predictive accuracy, 77% (95% CI, 54-100%). CONCLUSION: The combination of
      electrophysiologic intensities and tumor size are reproducible and better
      predictors of initial facial nerve function than any individual parameter, but
      long-term facial nerve function is more likely to have a better outcome if the
      nerve is left intact and a per-operative graft repair is not performed. The study
      suggests that although the best available predictor of overall long-term facial
      nerve outcome is the level of early postoperative function, this factor is not
      useful in surgical rehabilitation decision making.

PMID- 11981401
TI  - Sensory auricular branch of the facial nerve.
AB  - GOAL: To better describe the anatomy of the sensory auricular branch of the
      facial nerve. BACKGROUND: Clinical experience and the medical literature suggest
      that the facial nerve supplies sensory fibers to the external auditory canal and
      pinna. The anatomic distribution of these fibers remains poorly defined. METHODS:
      Ten cadaveric temporal bone dissections with photographic documentation, two
      clinical cases, and histologic examination of a candidate nerve fiber were
      collected. RESULTS: The anatomic distribution and histologic confirmation of a
      facial nerve branch coursing through the posterior wall of the external auditory
      canal is described. Mean (+/-SD) measurements along the mastoid segment of the
      facial nerve from the short process of the incus and chorda tympani nerve origin
      to the auricular branch origin were 11.6 +/- 1.4 mm (range 9-13 mm) and 3.9 +/-
      3.0 mm (range 0-8 mm), respectively. Sacrifice of this nerve in a patient
      resulted in posterior external auditory canal and inferior conchal bowl
      hypesthesia. CONCLUSION: The anatomy of a facial nerve branch coursing through
      the external auditory canal is presented. The anatomic and functional findings of
      this study suggest that this nerve represents an auricular sensory branch.
      Understanding these anatomic details may help in identifying the main trunk of
      the facial nerve in surgery, preventing postoperative external auditory canal
      hypesthesia, as well as understanding the significance of Ramsay-Hunt Syndrome
      and Hitselberger's Sign.

PMID- 11981402
TI  - Apoptosis and expression of BCL-2 in facial motoneurons after facial nerve
      injury.
AB  - BACKGROUND: Apoptosis has been implicated in neuronal degeneration after optic
      and sciatic nerve injury. The mechanisms contributing to facial motoneuron death
      are poorly understood. This study investigated the mechanisms underlying facial
      motoneuronal death and the expression of BCL-2 in facial motoneurons after facial
      nerve injury. METHODS: Morphologic changes in the facial motoneurons were
      examined by light and transmission electron microscopy, and TdT-mediated dUTP
      biotin nick end labeling (TUNEL) methods was used. Expression of BCL-2 was
      studied by immunohistochemistry and in situ hybridization after facial nerve
      injury. RESULTS: Cell shrinkage, condensed cytoplasm, and apoptotic bodies were
      demonstrated in numerous cells under light microscopy. The chromatin was
      condensed and localized to the nuclear envelope, forming a crescent or cap, and
      the endoplasmic reticulum was still visible but appeared swollen under electron
      microscopy. In vivo TUNEL staining displayed positive facial motoneurons 7 days
      after facial nerve transsection. The BCL-2 expression in facial motoneurons
      declined and reached its lowest level on the fifteenth day (p < 0.05). The
      reduction in BCL-2 expression after facial nerve transsection close to the facial
      motoneuron nucleus was greater than that of facial nerve transsection far away
      from the facial motoneuron nucleus (p < 0.05). BCL-2 expression after crushing of
      the facial nerve was found to be more intense in comparison with that after nerve
      transsection at the stylomastoid foramen (p < 0.05). CONCLUSIONS: These findings
      indicated that motoneuron death induced by facial nerve transsection was
      consistent with the process of apoptosis. The endogenous BCL-2 in these
      motoneurons may protect facial motoneurons from axotomy-induced cell death.

PMID- 11981403
TI  - Fibrous dysplasia of the temporal bone.

PMID- 11981404
TI  - Aberrant carotid artery.

PMID- 11981406
TI  - Increasing the efficacy of current available treatments.

PMID- 11981407
TI  - Hematopoietic stem cells from the marrow of mice treated with Flt3 ligand are
      significantly expanded but exhibit reduced engraftment potential.
AB  - BACKGROUND: Hematopoietic stem cells (HSC) can be significantly expanded by
      hematopoietic growth factors. Flt3 ligand (FL) is a hematopoietic growth factor
      that induces proliferation and mobilization of HSC into the peripheral blood. We
      previously reported that FL-mobilized HSC exhibit superior engraftment potential.
      The engraftment potential of FL-expanded HSC in the bone marrow compartment has
      not been evaluated. In this study, we investigated the effect of in vivo
      administration of FL on the engraftment potential of HSC expanded in the marrow.
      METHODS: B10.BR (H-2k) donor mice were treated for 10 days with 10 microg of FL
      per day. Partially conditioned allogeneic B10 (H-2b) recipients received whole
      bone marrow. Purified HSC (c-Kit+/Sca1+/lin-) from the marrow were also
      transplanted in ablated syngeneic B10.BR recipients. RESULTS: FL treatment
      significantly expanded HSC in the marrow compartment. The absolute number of T
      cells and granulocytes were unchanged whereas dendritic cells, facilitating
      cells, and HSC were significantly increased in the bone marrow of donor mice
      treated with FL compared with untreated mice. Mice conditioned with 700 cGy and
      transplanted with FL-treated allogeneic bone marrow showed a significantly lower
      rate of engraftment (14%) compared with recipients of bone marrow from untreated
      mice (100%). Syngeneic recipients transplanted with 500, 1000, 2000, or 3000
      purified HSC from FL-treated donors also showed reduced long-term survival
      compared with mice transplanted with HSC from untreated donors. Cell cycle
      analysis revealed that significantly more bone marrow HSC were in cycle after FL
      treatment compared with unmanipulated controls. CONCLUSION: These data show that
      FL treatment for 10 days induces proliferation of HSC but reduces the engraftment
      potential of HSC harvested from the marrow. The reduced syngeneic engraftment of
      HSC indicates that FL treatment induces intrinsic changes in HSC, resulting in
      failure of long-term engraftment or self-renewal despite no change in
      characteristic phenotype of HSC.

PMID- 11981408
TI  - Amelioration of myocardial global ischemia/reperfusion injury with volume
      regulatory chloride channel inhibitors in vivo.
AB  - BACKGROUND: Recently, the apoptotic volume decrease was suggested to be regulated
      by volume regulatory Cl- channels in cultured cell lines. We thus examined
      whether inhibition of volume-regulatory Cl- channels is cardioprotective, like
      caspase inhibition, by hindering the apoptosis of cardiomyocytes induced by
      global ischemia/reperfusion (I/R) in vivo. METHODS: We performed global ischemia
      for 8 min at 37 degrees C or 4 degrees C in isolated rat hearts, followed by 24
      hr reperfusion via heterotopic heart transplantation. The heart tissue was
      examined by means of the terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling (TUNEL) method, genomic DNA electrophoresis, and caspase-3 activity.
      Two blockers of volume-regulatory Cl- channels, 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), and a
      broad-spectrum caspase inhibitor, benzoyloxycarbonyl-Asp-CH2OC(O)-2,6
      dichlorobenzene (Z-Asp-DCB), were administered intravenously.
      Triphenyltetrazolium chloride (TTC) staining and ultrasound cardiography were
      performed to examine myocardial viability. The TTC-unstained region was assessed
      by means of horseradish peroxidase (HRP) infiltration and the TUNEL method.
      RESULTS: The transplanted hearts showed TUNEL-positivity and DNA laddering with a
      peak at 24 hr during reperfusion after ischemia at 37 degrees C, but not at 4
      degrees C. NPPB and DIDS were as potent as Z-Asp-DCB for recovery of cardiac
      function and for blocking the appearance of TUNEL-positivity, DNA laddering,
      caspase 3 activity, and a TTC-unstained area. TTC-unstained areas were composed
      of either TUNEL- and slightly HRP-positive or TUNEL-negative and strongly HRP
      positive cardiomyocytes. CONCLUSION: The present results demonstrated that
      myocardial DNA fragmentation, caspase activation, and loss of cardiac function
      after global I/R were blocked by NPPB and DIDS, similar to in the case of Z-Asp
      DCB. These results suggest that inhibition of volume-regulatory Cl- channels is
      also effective for preventing cardiac I/R injury.

PMID- 11981409
TI  - Prolonged function of extracorporeal hDAF transgenic pig livers perfused with
      human blood.
AB  - BACKGROUND: The development of genetically modified pigs has renewed interest in
      the use of porcine liver perfusion in the treatment of acute liver failure.
      METHOD: A previously developed model of extracorporeal perfusion has been used to
      test the function of porcine livers transgenic for human decay accelerating
      factor when perfused with fresh, whole, human blood. Three experimental groups
      were studied: alloperfusions (normal pig livers perfused with pig blood) and
      xenoperfusions of both unmodified and transgenic pig livers with human blood. All
      livers were perfused for up to 72 hr. RESULTS: Alloperfusion resulted in the
      maintenance of good function and histological structure. Stable hemodynamic,
      synthetic, and metabolic parameters were demonstrated in both unmodified and
      transgenic liver xenoperfusions; hyperacute rejection was not seen. In both
      groups, however, the measured parameters of liver function deteriorated toward
      the end of the 72 hr perfusion period; deterioration was more marked in the
      nontransgenic group. Xenoperfusions were characterized by a progressive and
      marked decrease in hematocrit of the circulating blood. Histologically, patchy
      necrosis was noted in both groups and more retained erythrocytes were seen in the
      sinusoids of nontransgenic livers, but no other consistent differences were
      apparent. CONCLUSIONS: These studies have demonstrated that porcine liver
      xenoperfusions can be performed for prolonged periods while maintaining good
      liver function. The use of organs from animals transgenic for a human complement
      regulator protein confers improvement in some measures of liver function. This
      preclinical model provides evidence that extracorporeal liver xenoperfusion may
      be effective in temporary liver support for patients in acute liver failure.

PMID- 11981410
TI  - Ischemic preconditioning: a defense mechanism against the reactive oxygen species
      generated after hepatic ischemia reperfusion.
AB  - BACKGROUND: Preconditioning protects against both liver and lung damage after
      hepatic ischemia-reperfusion (I/R). Xanthine and xanthine oxidase (XOD) may
      contribute to the development of hepatic I/R. OBJECTIVE: To evaluate whether
      preconditioning could modulate the injurious effects of xanthine/XOD on the liver
      and lung after hepatic I/R. METHODS: Hepatic I/R or preconditioning previous to
      I/R was induced in rats. Xanthine and xanthine dehydrogenase/xanthine oxidase
      (XDH/XOD) in liver and plasma were measured. Hepatic injury and inflammatory
      response in the lung was evaluated. RESULTS: Preconditioning reduced xanthine
      accumulation and conversion of XDH to XOD in liver during sustained ischemia.
      This could reduce the generation of reactive oxygen species (ROS) from XOD, and
      therefore, attenuate hepatic I/R injury. Inhibition of XOD prevented postischemic
      ROS generation and hepatic injury. Administration of xanthine and XOD to
      preconditioned rats led to hepatic MDA and transaminase levels similar to those
      found after hepatic I/R. Preconditioning, resulting in low circulating levels of
      xanthine and XOD activity, reduced neutrophil accumulation, oxidative stress, and
      microvascular disorders seen in lung after hepatic I/R. Inhibition of XOD
      attenuated the inflammatory damage in lung after hepatic I/R. Administration of
      xanthine and XOD abolished the benefits of preconditioning on lung damage.
      CONCLUSIONS: Preconditioning, by blocking the xanthine/XOD pathway for ROS
      generation, would confer protection against the liver and lung injuries induced
      by hepatic I/R.

PMID- 11981411
TI  - Successful extracorporeal porcine liver perfusion for 72 hr.
AB  - BACKGROUND: Improvements in extracorporeal perfusion technology and the
      production of transgenic pigs resistant to hyperacute rejection have stimulated
      several groups to re-explore the possibility of supporting patients in hepatic
      failure with extracorporeal porcine livers. The success of organ transplantation
      has also stimulated interest in using extracorporeal perfusion as a means of
      organ preservation and resuscitation of organs from marginal donors. The present
      study describes a method by which livers can be maintained in a viable condition
      for a minimum of 72 hr of normothermic, extracorporeal perfusion. METHODS: Five
      extracorporeal porcine liver perfusions were performed, each with a duration of
      72 hr. Hepatectomy was performed, followed by cold preservation, cannulation of
      vessels, and initiation of perfusion with normothermic, oxygenated porcine blood.
      Organ viability was assessed by metabolic, synthetic, hemodynamic, and histologic
      parameters. RESULTS: After 72 hr of normothermic, extracorporeal perfusion, the
      isolated livers demonstrated maintenance of normal physiological levels of pH and
      electrolytes. Continued hepatic protein synthesis (complement and factor V) was
      maintained throughout the perfusion. Hemodynamic parameters remained within
      normal physiological range. Histology demonstrated good preservation of the liver
      with no overall architectural change. CONCLUSION: It is possible to maintain a
      liver in a viable condition for a minimum of 72 hr of extracorporeal perfusion.
      This technique has been developed primarily as a preclinical model of
      extracorporeal liver support with the intention of proceeding to a clinical trial
      in patients with fulminant liver failure. However, it also has potential
      applications in organ preservation or resuscitation before transplantation and in
      the experimental study of isolated liver physiology.

PMID- 11981412
TI  - Brain death does not affect hepatic allograft function and survival after
      orthotopic transplantation in a canine model.
AB  - BACKGROUND: Brain death has been shown to decrease graft function and survival in
      rodent models. The aim of this study was to evaluate how brain death affects
      graft viability in the donor and liver tolerance to cold preservation as assessed
      by survival in a canine transplant model. METHODS: Beagle dogs were used for the
      study. Non-brain dead (BD) donors served as controls. Brain death was induced by
      sudden inflation of a subdural balloon catheter with continuous monitoring of
      arterial blood pressure and electroencephalographic activity. Sixteen hours after
      confirmation of brain death, liver grafts were retrieved. All livers were flushed
      in situ and preserved for 24 hr in cold University of Wisconsin solution before
      transplantation. Recipient survival rates, serum hepatic enzyme levels,
      coagulation, and metabolic parameters of the recipients were analyzed. RESULTS:
      No significant changes were observed in serum aminotransferases (alanine and
      aspartate transaminases) and lactate dehydrogenase levels in the BD donor. After
      preservation, control (n=6) and BD livers (n=5) showed full functional recovery
      after transplant with 100% survival in both groups at day 7. There was no
      significant difference in peak serum alanine, aspartate transaminases, and
      lactate dehydrogenase after transplantation in recipients who received a liver
      from BD donor compared to control group. BD livers were functionally as capable
      as control livers in correcting metabolic acidosis during the first 24 hr
      posttransplantation. Coagulation profiles (index normalized ratio, activated
      partial thromboplastin time) after reperfusion were similar between groups.
      CONCLUSION: In contrast to previous reports in rodent models, our study shows
      that brain death does not cause significant liver dysfunction in the donor before
      organ removal. Donor brain death and prolonged liver graft preservation do not
      interact significantly to impair liver function and survival after
      transplantation.

PMID- 11981413
TI  - Allochimeric class I MHC protein-induced tolerance by partial TCR engagement
      requires activation of both CTL4- and common gamma-chain-dependent cytokine
      signals.
AB  - BACKGROUND: The various toxicities associated with the general immune suppression
      resulting from current clinical immunosuppressive therapies continue to plague
      transplant recipients as well as jeopardize allograft survival. METHODS: The
      present study utilized allochimeric class I MHC antigens (alpha1hu70-77-RT1.Aa)
      bearing only four donor RT1.Au polymorphic amino acids (a.a.; His70, Val73,
      Asn74, and Asn77) superimposed on the recipient RT1.Aa background to induce
      transplantation tolerance in the rat cardiac transplant model. RESULTS: Oral
      delivery of alpha1hu70-77-RT1.Aa protein alone (days 0-6) induced tolerance, as
      evidenced by inhibition of both acute and chronic rejection processes. Delivery
      of alpha1hu70-77-RT1.Aa with therapeutic doses of cyclosporine (CsA) also
      prevented chronic rejection, otherwise readily developed after treatment with CsA
      alone. A polymerase chain reaction (PCR)-based analysis showed that tolerant
      recipients had reduced numbers of interleukin (IL)-2/interferon (IFN)-gamma
      producing T helper (Th)1 cells and elevated numbers of IL-4/IL-10-producing Th2
      cells. Adoptive transfer experiments revealed that potent regulatory T cells
      mediated tolerance. The same T cells displayed diminished T cell receptor (TCR)
      driven signaling via extracellular regulated kinase, AP-1, and NF-kappaB, as well
      as the common gamma-chain (gammac) cytokine-receptor-induced signaling by Janus
      kinase 3 (Jak3)/stimulators and activators of transcription Stat/5 pathways.
      Tolerance induction was prevented in vivo by inhibition of signal 2 by CTL4Ig or
      of signal 3 by either rapamycin, which disrupts the mammalian target of
      rapamycin, or AG490, which inhibits Jak3. Finally, partial or complete tyrosine
      phosphorylation of Zap70 was observed in alloantigen-specific T cell clones in
      response to tolerogenic versus immunogenic peptides, respectively. CONCLUSIONS:
      Tolerance induction by allochimeric proteins is achieved by partial TCR
      activation in the presence of signals 2 and 3, resulting in a skewed Th2
      phenotype.

PMID- 11981414
TI  - Isolation, short-term culture, and transplantation of small hepatocyte-like
      progenitor cells from retrorsine-exposed rats.
AB  - BACKGROUND: Complete liver regeneration after partial hepatectomy (PH) in rats
      treated with the pyrrolizidine alkaloid retrorsine can be accomplished through
      the activation, expansion, and differentiation of a novel population of small
      hepatocyte-like progenitor cells (SHPCs). These cells have not been isolated in
      pure form, established in primary culture, or transplanted into syngeneic rats to
      examine their differentiation potential. METHODS: Primary liver cells enriched
      for SHPCs were prepared by differential centrifugation of primary liver cell
      dispersions from retrorsine-exposed rats 6-8 days and 13-15 days after PH.
      Isolated SHPCs were characterized for cell size, morphology, and expression of
      cell type-specific markers (including hepatocyte and bile duct-oval cell
      markers), and established in short-term primary culture. Isolated SHPCs were
      transplanted into the livers of syngeneic rats to evaluate their ability to
      engraft and differentiate into mature hepatocytes. RESULTS: SHPCs obtained from
      retrorsine-exposed rats 6-8 days and 13-15 days after PH were small (10-12 microm
      in diameter), morphologically resembled hepatocytes, and were predominantly H.4
      antigen-positive, alpha-fetoprotein-positive, and OV6-negative. SHPCs did not
      proliferate in culture and could not be passaged, but short-term cultures were
      established using protein substrates (collagen or laminin) and defined medium
      containing epidermal growth factor and nicotinamide. After transplantation into
      the livers of syngeneic hosts, SHPCs insert into hepatic plates and give rise to
      differentiated hepatocyte progeny. The SHPC-derived hepatocyte progeny express a
      differentiated phenotype (albumin-positive, transferrin-positive, alpha
      fetoprotein-negative) and are able to proliferate in vivo in response to the
      growth stimulus provided by PH. CONCLUSIONS: The results demonstrate that
      enriched SHPC populations can be isolated from retrorsine-exposed rats and
      established in short-term culture, and they can engraft and differentiate after
      transplantation into the livers of syngeneic rats.

PMID- 11981415
TI  - Improved technique of portal vein reconstruction in pediatric liver transplant
      recipients with portal vein hypoplasia.
AB  - BACKGROUND: Children with small or hypoplastic portal veins represent a challenge
      for liver transplantation. Graft loss of up to 70% has been reported in these
      patients in the past. A variety of techniques has been used in both cadaveric and
      living related transplants in an effort to overcome this problem. Variability
      arises as to whether to use a vascular graft and where on the portal system to
      attach the graft. METHOD: We present our usage of a simple and straightforward
      interposition iliac vein allograft fashioned in a manner to achieve large
      anastomotic cross-sectional area on the confluence of the superior
      mesenteric/splenic veins. The procedure also overcomes problems of graft
      vein/portal vein size mismatch in the cases where liver and vein grafts are
      procured from much larger donors. RESULTS: A total of 14 children presented with
      hypoplastic portal vein (diameter<5 mm), of a total of 30 consecutive patients
      requiring cadaveric liver transplants, and benefited from this technique. Median
      recipient age was 10.5 months. Revascularization times ranged from 22 to 43 min
      with a mean of 33 min. All patients are alive and well at a mean follow-up of 329
      days (10 months). All liver grafts are well and functioning. No portal vein
      problem was detected. CONCLUSION: Results from this technique are clearly
      encouraging. Because portal vein hypoplasia is a common problem in pediatric
      transplant candidates, we believe this alternative technique is of interest and
      should be added to the transplant surgeon's armamentarium.

PMID- 11981416
TI  - Etiology of diarrhea in patients undergoing allogeneic bone marrow
      transplantation in South India.
AB  - BACKGROUND: No studies so far have examined enteric infections in patients
      undergoing bone marrow transplantation (BMT) in developing countries where
      asymptomatic carriage and colonization with enteric pathogens is frequent.
      METHODS: A prospective study followed 65 patients who underwent BMT in South
      India between 1995 and 1998. Patients were screened for enteric pathogens before
      transplantation, weekly during the first 4 weeks after transplantation, and
      during all episodes of diarrhea. RESULTS: Enteric pathogens were found in 60% of
      patients before or after transplantation. Pretransplantation screening revealed
      asymptomatic excretion of enteric pathogens in 29% (19/65). Forty-eight percent
      of patients undergoing BMT developed diarrhea. Diarrhea was mainly of
      noninfectious origin in the first 20 days after transplantation. More than 20
      days after transplantation, the major causes of diarrhea were graft-versus-host
      disease and infection. Parasitic infections other than Cryptosporidium did not
      contribute significantly to morbidity in the pre- and posttransplantation period.
      Rotavirus and adenoviruses were found in approximately 12% and 5% of subjects,
      respectively. Bacterial infections in the posttransplantation period were found
      to be more common in India than in developed countries. Clostridium difficile
      associated diarrhea was seen in the posttransplantation period but not before
      transplantation. Enterotoxigenic and enterohemorrhagic Escherichia coli caused
      symptomatic infections in the posttransplantation period, but the association of
      other classes of diarrheogenic E. coli with diarrhea was doubtful. CONCLUSIONS:
      There was significantly higher mortality (P<0.01) in patients with symptomatic or
      asymptomatic gastrointestinal infections caused by bacteria than in patients with
      parasitic or viral infections or without enteric infections.

PMID- 11981417
TI  - Maintenance of the celiac trunk with the left-sided liver allograft for in situ
      split-liver transplantation.
AB  - BACKGROUND: It has been shown that in situ split-liver transplantation (SLT)
      expands the cadaveric donor pool, decreases recipient waiting time, and decreases
      pretransplant morbidity. However, the technique as previously described requires
      a microvascular left hepatic artery anastomosis. In an attempt to decrease the
      incidence of hepatic artery thrombosis and to increase collaboration among
      transplant teams, in the current report, we describe a modification of the in
      situ SLT technique that maintains the celiac trunk with the left-sided liver
      allograft. METHODS: Twelve in situ split-liver procurements resulted in 24
      segmental liver allografts; 11 right trisegments, 11 left lateral segments, 1
      right lobe, and 1 left lobe. The common bile duct and main portal vein were
      maintained with the right-sided liver allograft in all cases. The right hepatic
      artery was divided, and the celiac trunk was maintained with the left-sided liver
      allograft in nine cases. In one case the left hepatic artery was divided and the
      celiac trunk was maintained with the right-sided allograft. Two of the 12 donors
      had a completely replaced left hepatic artery originating from the left gastric
      artery, which was divided at its origin from the celiac trunk. When the celiac
      trunk was maintained with the left-sided allografts, arterial reconstruction of
      the right-sided allograft was performed with an external iliac arterial
      interposition graft. Nineteen of the 24 split-liver allografts were transplanted
      at our center. The remaining five liver allografts were shared with regional
      liver transplant centers. RESULTS: In this series, 1-year actuarial patient and
      allograft survival rates are 100% and 96%, respectively. Hepatic artery
      thrombosis (HAT) did not occur in any patient receiving a left-sided split
      allograft in which the celiac trunk or left gastric artery was maintained; in
      addition, HAT did not occur in any of the right-sided allografts. HAT did occur
      immediately after transplantation in the one patient who was transplanted with a
      left lateral segment without the celiac trunk. This allograft was salvaged by
      early thrombectomy and interposition grafting. One patient required
      retransplantation, owing to portal vein thrombosis. Hepatic venous outflow
      obstruction did not occur in any of the patients. Two patients required
      reexploration in the posttransplant period because of arterial anastomotic site
      bleeding, and one of the left lateral segment allograft recipients had a cut
      surface bile leak, which was managed nonoperatively. All of the patients are
      alive and well, including the five patients who received their transplants at
      other centers, with a median follow-up of 10 months (range, 1-27 months).
      CONCLUSIONS: In summary, our data demonstrate that maintaining the celiac trunk
      with the left-sided allograft in SLT provides excellent early survival results
      with low complication rates. This technical modification obviates the need for a
      left hepatic artery microvascular anastomosis and should lower the incidence of
      hepatic artery thrombosis in the small-caliber left hepatic artery. We have also
      shown that this technique allows sharing among liver transplant centers without
      compromise in patient or allograft survival rates. It is hoped that this
      modification in SLT will increase the number of livers split, and will promote
      sharing among transplant centers to truly optimize the number of liver allografts
      available from the cadaveric pool.

PMID- 11981418
TI  - Risk factors for the development and progression of dyslipidemia after heart
      transplantation.
AB  - BACKGROUND: Hyperlipidemia is an important complication after organ
      transplantation and contributes to the development of posttransplant accelerated
      coronary artery diseases. METHODS: We have retrospectively evaluated the relative
      contribution of various risk factors associated with the development and
      progression of hyperlipidemia in 194 heart transplant recipients by the use of
      mixed effects multiple linear regression analysis. The demographic
      characteristics evaluated were primary diagnosis of ischemic heart disease (IHD),
      gender, and age. Postoperative characteristics included number of treated
      rejections, dosage of cyclosporine (CYA), tacrolimus (TAC), prednisolone and
      azathioprine, and concentration of serum creatinine and glucose. The effects of
      administration of antihypertensive agents, diuretics, and lipid lowering agents
      were also studied. RESULTS: The total cholesterol concentration increased
      significantly in the first 3 months posttransplant but gradually decreased
      thereafter. Total cholesterol and the ratio of low density lipoprotein (LDL)
      cholesterol to high density lipoprotein (HDL) cholesterol (LDL-C/HDL-C) increased
      to a greater extent in patients with IHD although female transplant recipients
      had a greater increase in the total cholesterol concentration. Each episode of
      rejection increased serum cholesterol by 0.306 mmol/liter (0.258, 0.355) [mean
      (95% C.I.)] and serum triglyceride by 0.164 mmol/liter (0.12, 0.209) although
      switching to TAC improved total cholesterol and LDL-C/HDL-C. Administration of
      frusemide, increased the total cholesterol and LDL-C/HDL-C whereas administration
      of bumetanide or metolazone increased the concentration of serum triglyceride.
      Serum glucose was associated with hypertriglyceridemia whereas serum creatinine
      was associated with increases in the total cholesterol, LDL-C/HDL-C and
      triglyceride. CONCLUSIONS: We have identified demographic and postoperative
      covariables that predispose heart transplant recipients to hyperlipidemia. Some
      of these risk factors, such as the effect of diuretics, have not been identified
      before in this group of patients and may be amenable to modification or closer
      control. TAC rather than CYA may be the immunosuppressive of choice for patients
      who are at greater risk of developing hyperlipidemia.

PMID- 11981419
TI  - Decreased serum and bronchoalveolar lavage levels of Clara cell secretory protein
      (CC16) is associated with bronchiolitis obliterans syndrome and airway
      neutrophilia in lung transplant recipients.
AB  - BACKGROUND: The major hinderance for long-term survival after lung
      transplantation is chronic rejection in the form of bronchiolitis obliterans
      syndrome (BOS). BOS is a fibrosing process in the small airways causing
      irreversible airway obstruction. BOS is associated with increased oxidative
      burden and activation of inflammatory and growth-stimulating mediators. The Clara
      cell secretory protein (CCSP or CC16) is a secreted differentiation marker for
      the bronchiolar epithelium with both antioxidative and
      antiinflammatory/immmunomodulatory properties. We asked whether this molecule
      could have a role in the development of BOS. METHODS: Serum and bronchoalveolar
      lavage (BAL) fluid samples were collected from 22 consecutive lung transplant
      recipients, the majority (19) was followed for 2 years. Six patients developed
      BOS. CCSP in serum was measured in 162 samples from 19 patients with an ELISA
      method, and CCSP in 191 BAL samples from 22 patients with quantitative Western
      blot. RESULTS: CCSP in both serum and BAL was significantly lower in BOS compared
      with acute rejection or no rejection. After the first postoperative month, serum
      and BAL CCSP levels were consistently lower in the patients who developed BOS
      than in those who did not. The percentage of neutrophils in BAL correlated
      negatively with CCSP in BAL. CONCLUSIONS: Levels of CCSP in serum and BAL is
      lowered in BOS. Serum CCSP could have a potential as an early marker for BOS. The
      correlation between decreased CCSP and increased neutrophils in BAL suggests a
      loss of local airway defense capacity in BOS.

PMID- 11981420
TI  - Kidney graft failure and presensitization against HLA class I and class II
      antigens.
AB  - BACKGROUND: It is well known that kidney transplant recipients with preformed
      lymphocytotoxic antibodies against HLA antigens have an increased graft rejection
      rate. However, the individual contribution of anti-HLA class I and class II
      antibodies to this phenomenon is poorly understood. We investigated the clinical
      relevance of preformed anti-HLA class I and class II antibodies on graft outcome
      in more than 4000 kidney recipients. METHODS: Pretransplant sera of 4136 cadaver
      kidney recipients from 28 transplant centers were tested in ELISA for IgG-anti
      HLA class I and IgG-anti-HLA class II antibodies. The influence of antibody
      reactivity on graft survival was analyzed. RESULTS: Four hundred eighty of the
      anti-HLA class I antibody-positive recipients had a graft survival rate at 2
      years of 77+/-2%, compared with an 84+/-1% rate in 3656 anti-HLA class I antibody
      negative recipients (P<0.0001), and 770 anti-HLA class II-positive recipients had
      a graft survival rate of 79+/-2%, compared with an 84+/-1% rate in 3366 anti-HLA
      class II-negative patients (P<0.0001). Importantly, good 2-year graft survival
      rates of 85+/-3% and 84+/-2%, respectively, were observed in 206 anti-HLA class I
      positive/class II-negative and 496 anti-HLA, class I-negative/class II-positive
      recipients. In contrast, the 274 recipients positive for both types of antibodies
      showed a poor graft survival rate of 71+/-3% (P<0.0001). Among 853 patients who
      received a well-matched kidney (0 or 1 HLA-A+B+DR mismatch), sensitization
      against either class I or class II, or both, had no deleterious effect. However,
      in 113 class I and class II antibody-positive patients who received a kidney with
      > or =3 HLA-A+B+DR mismatches, the 2-year graft survival rate was only 60+/-5%.
      CONCLUSION: Presensitization of first kidney transplant recipients against either
      HLA class I or class II is of no clinical consequence, whereas sensitization
      against both HLA class I and class II results in increased rejection of HLA
      mismatched grafts.

PMID- 11981421
TI  - Prospective trial of a predictive algorithm to transplant cadaver kidneys into
      highly sensitized patients.
AB  - BACKGROUND: The difficulty of transplanting sensitized patients increases
      proportionally to the panel reactive antibody (PRA) titer. Because of the high
      likelihood of a positive final crossmatch, these patients are often excluded from
      a prospective transplant unless there is a 0 HLA-A, -B, -DR mismatch. To address
      this problem, we developed a computerized algorithm, termed the Kentucky Antibody
      Testing System (KATS), that predicts class I HLA antigens that would be both
      "unacceptable" and "acceptable" to the recipient. This report describes the
      results of a prospective trial among voluntarily participating centers that
      agreed to share kidneys based on the KATS predictions for patients whose PRA
      exceeded 40%. METHODS: The results of three antibody screens on each patient were
      compared with the HLA phenotypes of the cells in the panel in 2x2 tables with
      calculation of chi-square and correlation coefficient statistics. Private, broad,
      and public antigens were identified and a list of acceptable and unacceptable
      antigens were entered into the UNOS computer for each patient listed in the KATS
      sharing algorithm. RESULTS: Of the total 418 patients meeting the
      inclusion/exclusion criteria, the largest single group submitted was Black-not-of
      Hispanic-origin females. The mean PRA of the patients was 72%. The first
      transplant via KATS allocation was performed on March 8, 1997. Between that time
      and the last transplant on July 31, 2000, 145 kidneys were offered to the
      participating centers and 48 transplants were performed. Of the many reasons
      listed for not accepting an offer or not transplanting the shared kidney into its
      intended recipient, only two occurred because of a positive T cell crossmatch and
      six because of a positive B cell crossmatch. As compared to all other high PRA
      patients within Southeastern Organ Procurement Foundation who were transplanted
      during the study period, they were more likely to be non-Caucasian, to be less
      well matched for private HLA-A, B, and DR antigens, and to have waited for a
      longer time than the other groups. Although there was a higher incidence of
      delayed graft function, there was no significant difference in cold ischemia,
      rejection episodes, or patient or graft survival. CONCLUSIONS: We conclude that
      KATS, or some other system to prospectively identify a list of acceptable and
      unacceptable HLA antigens, could improve the access of highly sensitized patients
      to a successful kidney transplant.

PMID- 11981422
TI  - Positive serum crossmatch as predictor for graft failure in HLA-mismatched
      allogeneic blood stem cell transplantation.
AB  - BACKGROUND: Evaluation of patient sera for complement-fixing anti-donor
      antibodies (serum crossmatch [XM]) before allogeneic blood stem cell
      transplantation (BSCT) is routine in most centers. However, in contrast to kidney
      transplantation, the predictive value of a positive XM for outcome of BSCT is
      still unclear, and a positive XM is presently not regarded as an absolute
      contraindication to proceed to transplant. METHODS: To clarify the role of a
      positive XM as predictor for overall survival (OS) and graft failure (GF) after
      BSCT, a retrospective, single-center, matched-pair analysis was performed.
      Enrolled were all XM-positive BSCT performed at our institution from 1985 to 2000
      (n=30). Controls (n=30) were matched for disease, disease stage, patient age,
      period of transplant, conditioning regimen, protocol for prevention of graft
      versus-host disease, and type of donor (related vs. unrelated, HLA-identical vs.
      HLA-mismatched). RESULTS: Multivariate statistical analysis of all enrolled 60
      transplants revealed GF as the all-dominating, independent risk factors for low
      OS (relative risk [RR]: 59.5, P<0.0001). Univariate (Kaplan-Meier) analysis could
      attribute inferior OS and high incidence of GF to the subgroup of HLA-mismatched,
      XM-positive transplants (P=0.01). CONCLUSIONS: A XM should always be performed in
      patients awaiting a BSCT from HLA-mismatched donors, because a positive XM is a
      predictor for inferior OS due to GF in BSCT.

PMID- 11981423
TI  - Primed CTLs specific for HLA class I may still be present in sensitized patients
      when anti-HLA antibodies have disappeared: relevance for donor selection.
AB  - BACKGROUND: The presence of donor-specific HLA antibodies is generally considered
      to be a contraindication for transplantation, even when these antibodies are only
      present in historical sera. Previous studies showed that donor-specific
      antibodies in current sera were associated with the presence of primed cytotoxic
      T cells (CTLs) with a high avidity for donor HLA class I antigens. The presence
      of these CTLs is considered to be a reflection of an activated immune system and
      a contraindication for transplantation with a donor sharing these particular HLA
      antigens. METHODS: In the present study we compared the incidence of primed CTLs
      in patients with anti-HLA antibodies in current sera and in patients with anti
      HLA antibodies in historical sera only. Cytotoxic T lymphocyte precursor (CTLp)
      frequencies and the incidence of primed CTLs directed against HLA class I
      antigens to which the patient had formed antibodies were studied in 37 sensitized
      renal patients. As controls, antigens to which a patient has never formed
      antibodies were tested. RESULTS: In patients with antibodies in current sera
      mainly primed CTLs were detected, whereas in patients where the antibodies had
      disappeared mainly naive CTLs were detected. However, in four patients primed
      CTLs persisted despite the fact that the HLA antibodies had disappeared.
      CONCLUSION: Considering the previously described association between primed CTLs
      and graft rejection, these findings may be relevant for the selection of patients
      who can be transplanted across a positive historical crossmatch. If the
      antibodies have disappeared and only naive CTLs are present, a successful
      transplantation should be feasible. A prospective study will reveal whether this
      is indeed the case.

PMID- 11981424
TI  - Chronic graft dysfunction in renal transplant patients: potential role of
      plasminogen activator inhibitor type 1.
AB  - BACKGROUND: Chronic allograft nephropathy is the main cause of long-term kidney
      graft loss. The plasminogen activator inhibitor type 1 (PAI-1) is a potential
      fibrogenic molecule whose secretion is regulated by several metabolic,
      inflammatory, and genetic factors. We aimed to determine whether PAI-1 secretion
      in renal transplant patients is correlated with the decline in renal function
      after transplantation. METHODS: Renal transplant patients (145 male/71 female)
      were included in the study 1-27 years after transplantation (median of follow-up:
      7.35 years). At inclusion, routine clinical and biological data were collected,
      the 4G/5G polymorphism of the recipient PAI-1 gene was determined, and the PAI-1
      plasma level was measured. RESULTS: The mean rate of decline in renal function
      was -4.26+/-0.30 ml/min/year. By multiple linear regression analysis, the rate of
      decline in renal function was significantly correlated with proteinuria
      (P=0.0176), occurrence of late acute rejection episodes (P=0.0001), and PAI-1
      plasma level (P=0.0051). In addition, PAI-1 plasma level was also significantly
      correlated with body mass index (P=0.038), insulin (P<0.0001), platelet count
      (P<0.0001), and fibrinogen (P=0.024). The PAI-1 gene polymorphism tested did not
      influence the rate of decline in renal function after transplantation nor the
      plasma level of PAI-1 antigen. CONCLUSION: We conclude that PAI-1, whose
      secretion is determined in large part by metabolic and inflammatory factors, may
      be implicated in the rate of decline in renal function after transplantation.

PMID- 11981425
TI  - Detection of a novel specificity (CTLA-4) in ATG/TMG globulins and sera from ATG
      treated leukemic patients.
AB  - BACKGROUND: T-cell costimulation has been shown to provide positive signals for T
      cell activation and generation of effector activity. In this study, we analyzed
      the presence of antibodies (Abs) against the T-lymphocyte costimulatory molecules
      CD28, CTLA-4, CD80, and CD86 in anti-T-lymphocyte (ATG) and antithymocyte (TMG)
      globulin preparations to address their mechanism of action. We focused our
      attention on the role of CTLA-4-specific Abs in the immunosuppressive effect of
      ATG/TMG, because anti-CTLA-4 agonistic Abs may suppress T-cell proliferation and
      nonagonistic Abs may lead to T-cell depletion through an Ab-dependent cell
      cytotoxicity mechanism. METHODS: ATG/TMG and patients' sera were tested for
      binding to recombinant human costimulatory molecules by ELISA techniques. CTLA-4
      specificity was also analyzed by cytoplasmic immunofluorescence staining of a
      CTLA-4 transfectant by competitive inhibition immunofluorescence and by cell
      proliferation assay in allogeneic mixed lymphocyte reaction (MLR). RESULTS:
      Either ATG or TMG predominantly contained anti-CTLA-4 Abs, with higher reactivity
      in ATG followed by anti-CD86 and -CD28 Abs, whereas anti-CD80 Abs were found only
      in ATG. Anti-CTLA-4 Abs present in ATG/TMG recognized the native form of CTLA-4
      molecule, and their removal reduced the effect of ATG in an allogeneic MLR.
      Kinetic studies indicated that such Abs were present in the sera of 12 ATG
      treated leukemic patients up to 21 days after ATG administration. CONCLUSIONS:
      These data suggest that the novel anti-CTLA-4 Abs found in ATG may greatly
      contribute to its immunosuppressive effect, thus accounting for the absence of
      rejection and exceptionally low incidence of graft-versus-host disease in the
      group of patients analyzed.

PMID- 11981426
TI  - Activation of human endothelial cells by mobilized porcine leukocytes in vitro:
      implications for mixed chimerism in xenotransplantation.
AB  - BACKGROUND: The induction of immunologic tolerance to pig antigens in primates
      may facilitate the development of successful clinical xenotransplantation
      protocols. The infusion of mobilized porcine peripheral blood leukocytes (PBPC,
      consisting of approximately 2% peripheral blood progenitor cells) into
      preconditioned baboons, intended to induce mixed hematopoietic cell chimerism,
      however, results in a severe thrombotic microangiopathy (TM) that includes
      vascular injury, microvascular thrombosis, and pronounced thrombocytopenia.
      Because the mechanisms responsible for TM are unclear, we have explored the
      effects of PBPC on human umbilical vein endothelial cell (HUVEC) activation.
      METHODS: Confluent HUVEC monolayers were established in 96-well cell culture
      clusters. PBPC were mobilized from miniature swine with porcine interleukin 3
      (pIL-3), porcine stem cell factor (pSCF), and human granulocyte-colony
      stimulating factor (hG-CSF) and were collected by leukapheresis. PBPC were added
      to HUVEC (0-1x10(7) PBPC/well) for 3- to 24-hr periods and, with cell-based ELISA
      techniques, surface levels of E-selectin, vascular cell adhesion molecule 1 (VCAM
      1), and intercellular adhesion molecule 1 (ICAM-1) were measured. In some cases,
      peripheral blood leukocytes (PBL) were collected from pigs that did not receive
      pIL-3, pSCF, or hG-CSF and were added to HUVEC. PBPC were also sorted into
      subsets of CD2- cells, CD2+ cells, and cellular debris, each of which were added
      separately to HUVEC. Transwell permeable membrane inserts were placed over HUVEC
      to prevent direct cell-cell contact with PBPC in some instances. RESULTS: PBPC
      from different pigs (n=6) induced an increase in the expression of E-selectin,
      VCAM-1, and ICAM-1 to levels 5, 4, and 2 times greater than baseline,
      respectively. ICAM-1 expression reached maximum levels after the addition of
      6x10(5) PBPC/well. Expression of E-selectin and VCAM-1 increased further with the
      addition of greater numbers of PBPC, reaching maximum levels after the addition
      of 1x10(7) PBPC/well. PBPC-induced up-regulation of E-selectin, VCAM-1, and ICAM
      1 had a maximum effect after approximately 6 hr, 12 hr, and 6 to 9 hr,
      respectively (n=3). The effects of fresh and frozen PBPC on HUVEC were similar
      (n=2). Compared to PBPC, PBL induced higher levels of E-selectin, VCAM-1, and
      ICAM-1 on HUVEC (n=2). The addition of CD2- cells to HUVEC induced an increase in
      E-selectin and VCAM-1 to levels 4 times greater than baseline, whereas the
      addition of CD2+ cells or debris did not elicit a substantial effect (n=2).
      Transwell permeable membranes prevented PBPC-induced up-regulation of E-selectin,
      VCAM-1, and ICAM-1 on HUVEC (n=2), suggesting that the mechanism of activation
      requires direct cell-cell contact. CONCLUSIONS: Porcine PBPC activate HUVEC, as
      suggested by an increase in surface E-selectin, VCAM-1, and ICAM-1 levels, and
      have a maximum effect after 9 hr. Freezing of PBPC does not affect PBPC-induced
      activation of HUVEC. PBL induce greater activation of HUVEC than do PBPC. CD2-
      cells are primarily responsible for PBPC-induced activation of HUVEC and direct
      cell-cell contact is required. Removal of CD2- cells before the administration of
      PBPC or the use of agents that interrupt PBPC-endothelial cell interactions may
      prevent or treat TM in baboons.

PMID- 11981427
TI  - Mechanisms of targeting CD28 by a signaling monoclonal antibody in acute and
      chronic allograft rejection.
AB  - There is increasing evidence that ongoing T-cell recognition of alloantigen and
      activation are key mediators of chronic allograft rejection. The CD28-B7 pathway
      is unique among costimulatory pathways in that two alternate ligands for B7
      exist: CD28 and CTLA4. Recently, it has been suggested that CTLA4 negative
      signaling may be required for induction of acquired tolerance in vivo. A strategy
      by which the T cell is targeted at the CD28 receptor rather than its ligands
      would theoretically allow the inhibitory functions of the CTLA4-B7-1/2 axis to
      remain intact. Using a rat-specific monoclonal antibody, we investigated the
      effect of targeting CD28 in a model of chronic rejection without the confounding
      variable of immunosuppression. We also used an acute cardiac allograft rejection
      model to investigate CD28 stimulation-based strategies to induce donor-specific
      tolerance. We demonstrated that anti-CD28 monoclonal antibody was as effective as
      CTLA4 immunoglobulin in protecting against chronic allograft vasculopathy. In
      addition, a short course of cyclosporine therapy synergized with either anti-CD28
      monoclonal antibody or CTLA4 immunoglobulin, suggesting that it may be clinically
      relevant to combine low-dose calcineurin inhibitors with CTLA4 immunoglobulin or
      anti-B7 antibodies. Finally, we report on the potential mechanisms of action of
      targeting CD28 in vivo.

PMID- 11981428
TI  - Macrophage colony-stimulating factor expression and macrophage accumulation in
      renal allograft rejection.
AB  - BACKGROUND: Studies of infiltrating cells from acutely rejecting renal allografts
      show that a high proportion of these cells are macrophages, and early macrophage
      infiltration is a poor prognostic sign for transplant survival. Macrophage colony
      stimulating factor (M-CSF), produced by tubular and mesangial cells, has been
      associated with macrophage infiltration and proliferation in experimental and
      human kidney diseases. We investigated the expression of M-CSF in a model of
      acute rejection. METHODS: Lewis rats underwent bilateral nephrectomies and
      received an orthotopic Dark Agouti allograft or Lewis isograft. Animals received
      cyclosporine (10 mg/kg/day) from day 0 to day 3 and were killed at days 4, 8, or
      14 after transplantation. Macrophages (ED1+) and T cells (W3-13+) were identified
      by immunohistochemistry, and M-CSF expression was identified by Northern blotting
      and in situ hybridization. RESULTS: Isografts had normal renal function without
      histological evidence of rejection. Allografts exhibited a moderate infiltrate at
      day 4 but progressed to severe rejection at day 14, with elevated serum
      creatinine level and severe tubulointerstitial damage. Macrophages and T cells
      were present in equal proportion in the infiltrate at day 4. At day 14, the
      number of macrophages increased fivefold (2580/mm2), although T cells were
      unchanged (380/mm2). Proliferating macrophages (ED1+, BrdU+) increased from day 4
      (4%) to day 14 (10%). M-CSF mRNA expression was strongly up-regulated in
      allografts compared with isografts and normal rat. In situ hybridization
      demonstrated M-CSF expression by resident and infiltrating cells. Renal tubular
      expression was minimally increased at day 4 but strongly up-regulated at day 14
      (more than 50% of tubules positive), particularly in areas of tubular damage.
      Tubular M-CSF expression colocalized with areas of intense macrophage
      infiltration and proliferation. Serial sections with double labeling demonstrated
      that T cells were the dominant source of M-CSF at day 4, yet later in the
      rejection (day 14) the predominant sites of production were both renal tubular
      cells and interstitial macrophages. CONCLUSIONS: Renal production of M-CSF by
      graft-infiltrating (macrophages and T lymphocytes) and resident (tubular) cells
      was up-regulated during acute rejection. M-CSF promotes macrophage recruitment
      and proliferation and may thereby play a pathogenic role in acute rejection. The
      kinetics of M-CSF production during acute rejection suggest that local macrophage
      proliferation may be initiated by T cells and perpetuated by both renal tubular
      and autocrine release.

PMID- 11981429
TI  - Delayed low-level calcineurin inhibition promotes allospecific tolerance
      induction by posttransplantation donor leukocyte infusion.
AB  - BACKGROUND: Donor lymphocytes infused after organ transplantation can have strong
      immunoregulatory effects. Application of such protocols for transplant tolerance
      induction in a clinical setting will, however, require combination of specific
      immunomodulatory strategies with nonspecific immunosuppressive medication for
      safety reasons. The aim of this study was to analyze the effects of
      immunosuppressive treatment on tolerance induction protocols by
      posttransplantation donor lymphocyte infusion. METHODS: The interaction of
      postoperative donor leukocyte infusion with different types, dosage, and timing
      of immunosuppressive drugs were studied in a rat model of heart transplantation.
      RESULTS: Tolerance could be achieved if donor cell infusion was combined with
      delayed, but not immediate, low-dose cyclosporine treatment, and this was
      associated with activation and apoptosis of host lymphocytes. In contrast,
      combinations with an antibody against the interleukin 2 receptor led to long-term
      graft survival but severe chronic rejection, and combinations with high-dose
      cyclosporine or sirolimus led to acute rejection. CONCLUSIONS: Postoperative
      donor leukocyte infusion is a potential way for tolerance induction, but the
      type, dose, and timing of medication are highly critical for its efficacy.

PMID- 11981430
TI  - New mouse model to study islet transplantation in insulin-dependent diabetes
      mellitus.
AB  - BACKGROUND: Islet transplantation studies with diabetic rodents frequently use
      treatment with diabetogens such as alloxan or streptozotocin to render hosts
      hyperglycemic. These chemicals produce unwanted toxic side effects, which
      complicate interpretations of damage produced by hyperglycemia versus direct
      toxin-induced damage. A mouse that spontaneously developed insulin-sensitive
      diabetes without beta-cell autoimmunity would provide an excellent vehicle for
      testing beta-cell replacement protocols. The Ins2Akita mutation disrupts normal
      insulin processing and causes a failure in secretion of mature insulins, which
      results in the early development of hyperglycemia. This report examines the
      insulin sensitivity of mice that carry Ins2Akita and their responsiveness to
      engraftment with syngeneic pancreatic islets. METHODS: Ten-week-old C57BL/6J
      Ins2Akita/+ males were given 1 unit of insulin to determine insulin sensitivity.
      Also, 10-week-old, hyperglycemic B6-Ins2Akita/+ received either 400 islets
      isolated from syngeneic C57BL/6J males (n=7) or from allogeneic BALB/cJ males
      (n=5) under the renal capsule. These mice were followed for 8 weeks after
      engraftment or until remission of euglycemia. Nephrectomy of the graft-containing
      kidney was performed on mice that remained euglycemic. These mice were then
      followed for 2 weeks for return of hyperglycemia. RESULTS: B6-Ins2Akita/+ mice
      are insulin responsive. Insulin treatment of hyperglycemic B6-Ins2Akita/+ males
      significantly lowered blood glucose values within 1 hr. In addition, B6
      Ins2Akita/+ recipients of syngeneic islet grafts reversed their diabetic state in
      less than 72 hr. These islet-engrafted mice remained normoglycemic until removal
      of the graft-containing kidney. Removal of the graft resulted in a return to
      hyperglycemia. Mice that received allogeneic grafts efficiently rejected the
      graft. CONCLUSIONS: Our data support the hypothesis that B6-Ins2Akita/+ mice are
      insulin sensitive and provide an excellent model for islet transplantation
      studies. In addition, the reduced beta-cell mass and the absence of beta-cell
      autoimmunity, coupled to the fact that these mice also reject allografts, suggest
      that these mice may be useful for a variety of other applications, including
      testing functionality of human islets prepared for transplantation and perhaps
      also for exploring beta-cell restorative therapy using pancreatic islet stem
      cells.

PMID- 11981431
TI  - Reconstitution of naive T cells and type 1 function after autologous peripheral
      stem cell transplantation: impact on the relapse of original cancer.
AB  - BACKGROUND: Phenotypic and functional reconstitution of T cells after peripheral
      blood stem cell transplantation (PBSCT) and its influence on posttransplant
      immune status is important in terms of immune surveillance and relapse of
      original cancer. We investigated the relationship between the dominant immune
      reconstitution pathway and the immune surveillance. We also tested the cytokine
      bias acquired by T cells after transplantation and its possible influence on
      relapse of original malignancy. METHODS: Immunophenotyping of naive and memory T
      cells was performed by flow cytometry on patients who underwent PBSCT for various
      cancers. Cytokine production by peripheral memory helper (CD4) and cytotoxic
      (CD8) T cells was investigated at various pretransplant and posttransplant time
      points with fluorescein isothiocyanate-based intracellular cytokine assay after
      short-term in vitro mitogenic stimulation (phorbol myristate acetate +
      ionomycin). Data on T-cell subsets and polarized cytokines gamma-interferon (Ifn)
      and interleukin 4 produced by memory T cells were compared with that of healthy
      controls. RESULTS: The reconstitution of naive T cells and gamma-Ifn-producing
      memory cells was significantly lower in patients who experienced relapse of
      original cancer within 1 year of PBSCT compared to those who showed no signs of
      relapse even after 2 years and compared to normal subjects. The results indicate
      that efficient reconstitution of naive T cells and type 1 function of memory T
      cells are important in maintaining T-cell repertoire diversity after PBSCT. It
      also confers appropriate levels of immune surveillance against diverse
      neoantigens that evolve from residual tumor burden. The data reveal that
      chemotherapy-induced thymic injuries may impair regeneration of naive cells that
      result in a naivopenic state in a susceptible host. CONCLUSIONS: The study
      highlights the importance of naive T-cell reconstitution and points towards cell
      replacement strategies for improving immune surveillance after PBSCT.

PMID- 11981432
TI  - CD3 monitoring of antithymocyte globulin therapy in thoracic organ
      transplantation.
AB  - BACKGROUND: Antithymocyte globulin is frequently used as a component of induction
      therapy in thoracic organ transplantation. This study evaluates the utility of
      monitoring peripheral CD3 lymphocytes to rationally adjust antithymocyte globulin
      therapy in this patient population. METHODS: A total of 17 heart and 19 lung
      transplant recipients received antithymocyte globulin (ATGAM or thymoglobulin) as
      induction therapy or to treat steroid-resistant acute or chronic rejection.
      Absolute CD3 counts were maintained between 50 and 100 cells/microl. RESULTS:
      With CD3 monitoring, the doses of antithymocyte globulin were reduced from 10-15
      mg/kg to 1-5 mg/kg during the course of therapy. The total amount of
      antithymocyte globulin given to each CD3 monitored patient was reduced by 48%.
      Dose reduction did not alter the number of acute rejection or infectious
      episodes, and hematological side effects were infrequent. CONCLUSION: CD3
      monitoring of antithymocyte globulin therapy in thoracic organ recipients reduced
      the amount of drug received by each patient, while maintaining CD3 counts less
      than 100 cells/microl.

PMID- 11981433
TI  - Cytokine gene polymorphisms in children successfully withdrawn from
      immunosuppression after liver transplantation.
AB  - BACKGROUND: Cytokine genetic polymorphisms have been associated with transplant
      outcome in some experimental and clinical studies, but the cytokine profile of
      patients who are clinically tolerant has not been investigated. AIM: Allelic
      variations in tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma,
      transforming growth factor (TGF)-beta1, interleukin (IL)-6, and IL-10 were
      evaluated in patients successfully withdrawn from immunosuppression. METHODS:
      Pediatric liver transplant recipients who were successfully withdrawn from
      immunosuppression (n=12) or who are on minimal immunosuppression (n=7) were
      genotyped. A control group of liver recipients who required maintenance
      immunosuppression served as a control group (n=37). RESULTS: Compared to the
      control group, low TNF- alpha and high/intermediate IL-10 profiles were seen in
      all 12 children maintained off immunosuppression and in 6 of 7 children requiring
      minimal immunosuppression. CONCLUSION: Children successfully maintained off
      immunosuppression are more likely to have a genetic predisposition toward low TNF
      alpha and high/intermediate IL-10 production. Children maintained on minimal
      immunosuppression exhibit a similar cytokine profile to those successfully
      weaned.

PMID- 11981434
TI  - The risk of cardiovascular disease associated with proteinuria in renal
      transplant patients.
AB  - Proteinuria in the general population has been shown to be associated with
      cardiovascular disease, which is the main cause of death in renal
      transplantation. We investigated the effect of proteinuria on cardiovascular
      disease after renal transplantation in 532 renal transplant patients with
      functioning grafts for more than 1 year. Patients were classified into two groups
      depending on the presence of persistent proteinuria. We analyzed graft and
      patient survival, posttransplantation cardiovascular disease, and main causes of
      graft loss and death. Five- and 10-year graft and patient survival rates were
      lower in the group with proteinuria. The main cause of death was vascular disease
      in both groups. The presence of posttransplantation cardiovascular disease was
      higher in the group with proteinuria. Persistent proteinuria was associated with
      graft loss (RR=4.18), patient death (RR=1.92), and cardiovascular disease
      (RR=2.45). In conclusion, persistent proteinuria was an independent risk factor
      for increased cardiovascular morbidity and mortality in renal transplant
      patients.

PMID- 11981435
TI  - Duct-to-duct biliary reconstruction in living-related liver transplantation.
AB  - BACKGROUND: Bile duct-to duct reconstruction is now used in living-related liver
      transplantation for adult patients. However, the feasibility remains
      controversial. METHODS: Bile duct-to-duct reconstruction was performed in 25
      adult patients. In the total hepatectomy of the patients, the hilar plate was
      dissected at the second-order branch of the bile ducts. The anastomosis was
      performed using an interrupted suture with an external stent tube. A C tube was
      inserted from the stump of the cystic duct and introduced into the duodenum.
      RESULTS: All of the patients survived the operation. During the observation
      period ranging from 34 to 345 days, biliary complications were observed in 8%
      cases. Dilation of the bile ducts and an absence of bile output were recognized
      in one patient each, and necessitated surgical revision. CONCLUSIONS: Our
      preliminary experience in biliary reconstruction seems to warrant its long-term
      observation in the postoperative period.

PMID- 11981436
TI  - Polyomavirus nephropathy in native kidneys of a solitary pancreas transplant
      recipient.
AB  - BACKGROUND: Latent polyomavirus (PV) infection of the urinary tract can be
      reactivated by immunosuppression. When this occurs in the renal allograft,
      permanent loss of allograft function can occur. Polyomavirus reactivation could
      potentially affect the native kidneys of nonrenal transplant recipients and cause
      renal dysfunction. METHODS: This article describes a case of PV nephropathy in
      the native kidneys of a solitary-pancreas transplant recipient. This patient had
      a progressive increase in serum creatinine. Screening urine cytology showed
      numerous cells with cytopathic changes suggestive of polyomavirus infection.
      RESULTS: Biopsy of the native kidneys of this patient showed renal tubular cells
      with intranuclear inclusions characteristic of PV infection, which was confirmed
      by immunohistochemistry. Electron microscopy showed intranuclear viral particles.
      Patchy inflammation and fibrosis also were noted. CONCLUSION: Polyomavirus
      reactivation can occur in the native kidneys of nonrenal solid organ transplant
      recipients. This should be considered in the differential diagnosis of renal
      impairment in these patients. The effects of PV reactivation on long-term native
      kidney function are not known.

PMID- 11981437
TI  - Effect of HLA-DR matching on acute rejection after clinical heart transplantation
      might be influenced by an IL-2 gene polymorphism.
AB  - BACKGROUND: To examine whether genetic factors are involved in the development of
      acute rejection (AR), we investigated a (CA)m(CT)n repeat in the 3'-flanking
      region of the interleukin (IL)-2 gene. METHOD: We genotyped 290 heart transplant
      recipients with and without AR (International Society for Heart and Lung
      Transplantation criteria > or =3A) and 101 controls. RESULTS: The frequency of
      allele 135 of the repeat and its genotype distribution (carriers/noncarriers)
      were significantly associated with freedom from AR (P=0.03 and P=0.02,
      respectively). We also found interaction between allele 135 and HLA-DR matching.
      More carriers of allele 135 with no or one mismatch remained free from AR
      compared to patients without the allele (P=0.01). This was not found in the HLA
      DR group with two mismatches. CONCLUSION: HLA-DR matching might only be effective
      in reducing AR after heart transplantation in recipients who carry allele 135 of
      the (CA)m(CT)n repeat in the 3'-flanking region of the IL-2 gene.

PMID- 11981438
TI  - Kidney transplantation in the elderly: age-matching as compared to HLA-matching:
      a single center experience.
AB  - BACKGROUND: We report the short-term outcome of our patients participating within
      the Eurotransplant age-matching program, where kidneys from donors >65 years are
      transplanted to recipients >65 years regardless of human leukocyte antigen (HLA)
      compatibility but with short cold ischemia times, in comparison with patients >60
      years transplanted with HLA-matching. METHODS: Twenty-five patients (66.7+/-2.6
      years) (donors 69+/-4.3 years) participated in this program (group A). The
      control group consisted of 21 patients (63+/-2.6 years) (group B) (donors 47.6+/
      17.3 years). RESULTS: Despite significant differences in donor age, cold ischemia
      time (12.3+/-4.6 hr in A, 22.8+/-4.8 hr in B, P<0.001) and a mean of 4.4+/-1.4
      vs. 2.3+/-1.6 HLA-mismatches (P<0.001), there was no difference regarding the
      incidence of delayed graft function (64 vs. 57%), rejections (52 vs. 66.7%),
      infections (56 vs. 52.4%), and other complications (80 vs. 71.4%). Mean serum
      creatinine after 6 months was 1.94+/-0.49 and 1.83+/-0.67 mg/dl (NS). CONCLUSION:
      The short-term results of the age-matching program are promising and comparable
      with results from patients of similar age with HLA-matching.

PMID- 11981439
TI  - Liver transplant with organs from elderly donors: Spanish experience with more
      than 300 liver donors over 70 years of age.

PMID- 11981440
TI  - Financial incentives for cadaver organ donation: an ethical reappraisal.
AB  - A panel of ethicists, organ procurement organization executives, physicians, and
      surgeons was convened by the sponsorship of the American Society of Transplant
      Surgeons to determine whether an ethically acceptable pilot trial could be
      proposed to provide a financial incentive for a family to consent to the donation
      of organs from a deceased relative. An ethical methodology was developed that
      could be applied to any proposal for monetary compensation to elucidate its
      ethical acceptability. An inverse relationship between financial incentives for
      increasing the families' consent for cadaver donation that clearly would be
      ethically acceptable (e.g., a contribution to a charity chosen by the family or a
      reimbursement for funeral expenses) and those approaches that would more likely
      increase the rate of donation (e.g., direct payment or tax incentive) was
      evident. The panel was unanimously opposed to the exchange of money for cadaver
      donor organs because either a direct payment or tax incentive would violate the
      ideal standard of altruism in organ donation and unacceptably commercialize the
      value of human life by commodifying donated organs. However, a majority of the
      panel members supported reimbursement for funeral expenses or a charitable
      contribution as an ethically permissible approach. The panel concluded that the
      concept of the organ as a gift could be sustained by a funeral reimbursement or
      charitable contribution that conveyed the appreciation of society to the family
      for their donation. Depending on the amount of reimbursement provided for funeral
      expenses, this approach could be ethically distinguished from a direct payment,
      by their intrusion into the realm of altruism and voluntariness. We suggest that
      a pilot project be conducted to determine whether this kind of a financial
      incentive would be acceptable to the public and successful in increasing organ
      donation.

PMID- 11981441
TI  - Endotoxin and anti-endotoxin. The contribution of the schools of Koch and
      Pasteur: life, milestone-experiments and concepts of Richard Pfeiffer (Berlin)
      and Alexandre Besredka (Paris).

PMID- 11981442
TI  - Modulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin.
AB  - Nitric oxide (NO) is an endogenous vasodilator and modulator of inflammation.
      During endotoxemia, the beneficial effects of NO are overwhelmed by the
      inflammatory cascade, resulting in a functional depletion of NO. S-nitroso
      albumin (S-NO-alb) exists as a novel and highly stable NO thiol complex that
      slowly releases NO into the vascular micro-environment. Using a porcine model, we
      examined the ability of intravenous S-NO-alb to modulate cardiopulmonary
      dysfunction characteristic of endotoxemia. Pigs were anesthetized, instrumented
      for standard cardiopulmonary function measurements, and randomly assigned to
      receive: (i) albumin + saline; (ii) albumin + LPS; or (iii) S-NO-alb + LPS.
      Cardiopulmonary parameters were evaluated every 30 min and ex vivo phorbol
      myristate acetate (PMA)-stimulated superoxide release was serially determined as
      a marker of in vivo neutrophil priming. Lung myeloperoxidase (MPO) activity was
      measured as a marker of neutrophil migration into the lung. LPS-induced
      cardiopulmonary dysfunction was characterized by a sustained elevation in mean
      pulmonary arterial pressure, pulmonary vascular resistance, and peak
      intratracheal pressure, as well as a reduction in cardiac index, stroke volume
      index and PaO(2) over 6 h. Pretreatment with S-NO-alb attenuated LPS-induced
      cardiopulmonary dysfunction without adversely affecting systemic hemodynamics.
      Moreover, S-NO-alb blunted the LPS-induced hypoxemic response and reduced
      neutrophil activation. S-NO-alb did not, however, attenuate LPS-induced increases
      in lung MPO. Our results suggest that S-NO-alb can selectively modulate endotoxin
      induced pulmonary dysfunction, attenuate neutrophil priming and block the early
      mortality (40%) in this model.

PMID- 11981443
TI  - Identification of genes involved in biosynthesis of Actinobacillus
      pleuropneumoniae serotype 1 O-antigen and biological properties of rough mutants.
AB  - Actinobacillus pleuropneumoniae is an important pathogen of swine.
      Lipopolysaccharide (LPS) has been identified as the major adhesin of A.
      pleuropneumoniae and it is involved in adherence to porcine respiratory tract
      cells. We previously generated seven rough LPS mutants of A. pleuropneumoniae
      serotype 1 by using a mini-Tn10 transposon mutagenesis system [Rioux S, Galarneau
      C, Harel J et al. Isolation and characterization of mini-Tn10 lipopolysaccharide
      mutants of Actinobacillus pleuropneumoniae serotype 1. Can J Microbiol 1999; 45:
      1017-1026]. The purpose of the present study was to characterize these mutants in
      order to learn more about LPS O-antigen biosynthesis genes and their organization
      in A. pleuropneumoniae, and to determine the surface properties and virulence in
      pigs of these isogenic mutants. By mini-Tn10 insertions in rough mutants, four
      putative genes (ORF12, ORF16, ORF17, and ORF18) involved in O-antigen
      biosynthesis in A. pleuropneumoniae serotype 1 were found within a region of 18
      ORFs. This region is homologous to the gene cluster of serotype-specific O
      polysaccharide biosynthesis from A. actinomycetemcomitans strain Y4 (serotype b).
      Two mutants showed homology to a protein with identity to glycosyltransferases
      (ORF12); two others had the mini-Tn10 insertion localized in genes encoding for
      two distinct proteins with identity to rhamnosyltransferases (ORF16 and ORF17)
      and three showed homology to a protein which is known to initiate polysaccharide
      synthesis (ORF18). These four ORFs were also present in A. pleuropneumoniae
      serotypes 9 and 11 that express an O-antigen that serologically cross-reacts with
      serotype 1. Evaluation of some biological properties of rough mutants seems to
      indicate that the absence of O-chains does not appear to have an influence on the
      virulence of the bacteria in pigs and on the overall surface hydrophobicity,
      charge and hemoglobin-binding activity, or on LAL activation. An acapsular mutant
      was included in the present study in order to compare the influence of O-chains
      and capsule polysaccharides on different cell surface properties. Our data
      suggest that capsular polysaccharides and not O-chains polysaccharides have a
      major influence on surface properties of A. pleuropneumoniae serotype 1 and its
      virulence in pigs.

PMID- 11981444
TI  - The biological activity of a liposomal complete core lipopolysaccharide vaccine.
AB  - A vaccine that induces humoral immunity to lipopolysaccharide (LPS), while
      remaining non-pyrogenic should be beneficial, as high levels of antibodies
      against LPS are associated with a reduced risk of adverse outcome. However, pure
      LPS or bacteria expressing LPS are generally considered too toxic to be used as
      vaccines. Recently, a novel, immunogenic complete core lipopolysaccharide vaccine
      has been described, which has been designed to prevent endotoxin-related
      inflammatory reactions in surgical and high-risk hospitalized patients. In vivo
      studies have shown that while administration of the vaccine to rabbits results in
      no toxicity over 7 days, it does induce significantly enhanced antibody responses
      towards a broad range of clinically relevant Gram-negative LPSs. Here we show
      that encapsulation of the four complete core LPS types Escherichia coli K12,
      Escherichia coli R1, Bacteroides fragilis and Pseudomonas aeruginosa into
      liposomes greatly reduces the ability of a given amount of LPS to induce TNF
      alpha production in vitro from human monocytes. In contrast to previous studies
      of liposomal LPS, we demonstrate a reduction in activity of approximately 100,000
      fold; a reduction approximately 100-1,000-fold more than that previously
      described. The signalling by the liposomal LPS appears to be entirely dependent
      on serum factors, though this can be partially restored by soluble CD14 or, to a
      lesser extent, by lipopolysaccharide binding protein. Time-course experiments
      reveal that liposomal LPS signalling shows similar kinetics to pure LPS
      signalling. Therefore, as well as inducing specific antibody responses, liposomal
      LPS demonstrates characteristics suitable for use as a vaccine to be used in
      human beings.

PMID- 11981445
TI  - Phase variable changes in genes lgtA and lgtC within the lgtABCDE operon of
      Neisseria gonorrhoeae can modulate gonococcal susceptibility to normal human
      serum.
AB  - The alpha-chain of the core oligosaccharide of the lipo-oligosaccharide (LOS)
      produced by Neisseria gonorrhoeae can undergo reversible and rapid changes in
      structure due to phase-variable production of certain enzymes employed in the
      biosynthesis of the lacto-N-neotetraose structure. Five of these enzymes are
      encoded by the lgtABCDE operon, and polynucleotide tracts within three of these
      genes (lgtA, lgtC and lgtD) can be substrates for slipped-strand mispairing
      events that lead to nucleotide insertions or deletion events which result in
      variable production of their respective gene products. We now report that phase
      variable synthesis of the lgtA and lgtC gene products in strain FA19 results in
      the production of elongated LOS alpha-chains and that the presence of these LOS
      species can result in gonococci being sensitive to the bacteriolytic action of
      serum-antibody and complement. Hence, phase variation within the lgtABCDE operon
      can significantly impact the ability of gonococci to subvert this important host
      defense system.

PMID- 11981446
TI  - IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration
      following endotoxemia.
AB  - The influx of neutrophils into tissues in response to inflammatory stimuli
      involves C-X-C chemokines. Interleukin-1 (IL-1) stimulates chemokine production
      in vitro, but its role in vivo on chemokine production is not as clearly
      understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine
      production induced by systemic lipopolysaccharide (LPS). IL-1 activity was
      blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella
      typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine
      induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein
      2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of
      organ injury were measured. LPS administration resulted in increased plasma,
      lung, and liver IL-1beta that was decreased by Il-1Ra. LPS also induced an
      increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However,
      IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In
      contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein
      expression in the liver (45% decrease) and MIP-2 protein expression in plasma
      (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS-
      treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC
      1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment
      with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil
      accumulation, respectively, following LPS. In addition, indices of both lung and
      liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS
      induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL
      1 dependent. Although lung neutrophil accumulation in both lung and liver after
      LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These
      data suggest that IL-1 regulates tissue chemokine expression and neutrophil
      accumulation after LPS.

PMID- 11981447
TI  - Building an ER electron transport chain.

PMID- 11981448
TI  - S-nitrosothiols control breathing and oxygen homeostasis.

PMID- 11981449
TI  - 3-Methylcholanthrene-inducible hepatic DNA adducts: a mechanistic hypothesis
      linking sequence-specific DNA adducts to sustained cytochrome P4501A1 induction
      by 3-methylcholanthrene.

PMID- 11981450
TI  - Redox control of iron regulatory proteins.
AB  - Iron regulatory proteins, IRP1 and IRP2, are cytoplasmic proteins of the iron
      sulfur cluster isomerase family and serve as major post-transcriptional
      regulators of cellular iron metabolism. They bind to 'iron responsive elements'
      (IREs) of several mRNAs and thereby control their translation or stability. IRP1
      and IRP2 respond to alterations in intracellular iron levels, but also to other
      signals such as nitric oxide (NO) and reactive oxygen species (ROS). The redox
      regulation of IRP1 and IRP2 provides direct links between the control of iron
      homeostasis and oxidative stress.

PMID- 11981451
TI  - Micellar effect on the scavenging of singlet molecular oxygen by hydroxybenzenes.
AB  - The antioxidative effectiveness of three hydroxyaromatic derivatives (OHAD),
      namely phenol, resorcinol and phloroglucinol, as reflected by their scavenging
      ability of the photochemically generated species singlet molecular oxygen
      [O(2)((1)Delta(g))], was studied in aqueous solution and micellar media. Kinetic
      results, obtained through time-resolved phosphorescence detection of
      O(2)((1)Delta(g)) emission and polarographic methods, at pH 7 and 12 in
      homogeneous and CTAB micellar media, were compared. Calculated photooxidation
      quantum efficiencies (phi(r)), ranging from very low values ( approximately 0.01)
      to relatively high ones (approximately 0.3), depend on the preferential
      solubilization sites of the hydroxyaromatic derivatives either in the micellar or
      homogeneous media. OHAD in water pH 7 and in CTAB 0.02 M pH 12 exhibit their
      highest antioxidative efficiency as O(2)((1)Delta(g)) scavengers. In these
      conditions, they present the best degree of self protection against
      O(2)((1)Delta(g))-mediated photooxidation with relatively high values for the
      overall quenching rate constant and, simultaneously, the lowest phi(r).

PMID- 11981452
TI  - Phospholipase C-dependent hydrolysis of phosphatidylcholine hydroperoxides to
      diacylglycerol hydroperoxides and its reduction by phospholipid hydroperoxide
      glutathione peroxidase.
AB  - We have shown that 1,2-diacylglycerol hydroperoxides activate protein kinase C
      (PKC) as efficiently as does phorbol ester [Takekoshi S, Kambayashi Y, Nagata H,
      Takagi T, Yamamoto Y, Watanabe K. Activation of protein kinase C by oxidized
      diacylglycerol. Biochem Biophys Res Commun 1995; 217: 654-660]. 1,2
      Diacylglycerol hydroperoxides also stimulate human neutrophils to release
      superoxide whereas their hydroxides do not [Yamamoto Y, Kambayashi Y, Ito T,
      Watanabe K, Nakano M. 1,2-Diacylglycerol hydroperoxides induce the generation and
      release of superoxide anion from human polymorphonuclear leukocytes. FEBS Lett
      1997; 412: 461-464]. One of the proposed mechanisms for the formation of 1,2
      diacylglycerol hydroperoxides is the hydrolysis of phosphatidylcholine
      hydroperoxides by phospholipase C (PLC). To confirm this hypothesis, we incubated
      1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) liposomes containing PLPC
      hydroperoxides (PLPC-OOH) with Bacillus cereus PLC and found 1-palmitoyl-2
      linoleoylglycerol (PLG) and its hydroperoxide (PLG-OOH) were produced. PLC
      hydrolyzed the two substrates without preference, as the yields of PLG and PLG
      OOH were the same even though cholesterol was incorporated into liposomes to
      increase bilayer integrity. Phospholipid hydroperoxide glutathione peroxidase
      (PHGPX) reduced PLG-OOH to its hydroxide in the presence of glutathione while the
      conventional cytosolic glutathione peroxidase did not. These data suggest that
      PLC hydrolyzes oxidized biomembranes to give 1,2-diacylglycerol hydroperoxides
      for PKC stimulation but PHGPX may prevent neutrophil stimulation by reducing 1,2
      diacylglycerol hydroperoxides to their hydroxides.

PMID- 11981453
TI  - Free radical scavenging activity of vanillin and o-vanillin using 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical.
AB  - Vanillin, a plant derived natural product, used as food flavoring agent and its
      positional isomer o-vanillin, have been tested for their ability to scavenge 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical using high performance liquid
      chromatography (HPLC). Trolox, a water-soluble analogue of vitamin E and a well
      known antioxidant was used as a reference compound. The DPPH radical was
      monitored at 517 nm and its retention time was 8.6 min. From the decrease in
      optical density of DPPH radical in the presence of the test compounds, it was
      observed that o-vanillin was a more effective scavenger than vanillin. At
      equimolar concentrations (1 mM), vanillin and o-vanillin exhibited 22.9% and
      66.4% DPPH radical scavenging activity, respectively. The kinetics of the
      reaction of vanillin and o-vanillin with DPPH radical was studied using stopped
      flow spectrophotometry and their rate constants were estimated to be 1.7 +/- 0.1
      M(-1)s(-1) and 10.1 +/- 0.8 M(-1)s(-1), respectively. In comparison, the rate
      constant for the reaction of trolox with DPPH was estimated to be 360.2 +/- 10.1
      M(-1)s(-1). These scavenging reactions involve electron/H-atom transfer from
      antioxidant to DPPH. To confirm this, one electron reduction potentials of these
      compounds were estimated using cyclic voltammetry which showed that o-vanillin
      was more easily oxidized than vanillin. The reduction potential for o-vanillin
      was about 1.5 times that of trolox. These results demonstrate that o-vanillin is
      a more potent antioxidant than vanillin.

PMID- 11981454
TI  - Antioxidant properties of gallocatechin and prodelphinidins from pomegranate
      peel.
AB  - Gallocatechins and a range of prodelphinidins were purified by high performance
      liquid chromatography from pomegranate peel. Gallocatechin, gallocatechin-(4-8)
      catechin, gallocatechin-(4-8)-gallocatechin and catechin-(4-8)-gallocatechin were
      all identified, purified and quantified by LC-DAD-MS and MS-MS. The antioxidant
      properties of these compounds were assessed using two methods: (i) inhibition of
      ascorbate/iron-induced peroxidation of phosphatidylcholine liposomes; and (ii)
      scavenging of the radical cation of 2,2-azinobis (3-ethyl-benzothiazoline-6
      sulphonate, ABTS) relative to the water-soluble vitamin E analogue Trolox C
      (expressed as Trolox C equivalent antioxidant capacity, TEAC). The prodelphinidin
      dimers were potent antioxidants in the aqueous phase, being much more effective
      than the gallocatechin monomer. However, in the lipid phase, only one of the
      dimers (gallocatechin-(4-8)-catechin) was significantly more effective than the
      monomer in the inhibition of lipid peroxidation of phosphatidylcholine vesicles.
      This study represents the first report on the antioxidant properties of
      prodelphinidins.

PMID- 11981455
TI  - Myeloperoxidase-dependent caspase-3 activation and apoptosis in HL-60 cells:
      protection by the antioxidants ascorbate and (dihydro)lipoic acid.
AB  - The heme enzyme myeloperoxidase (MPO) has recently been implicated in hydrogen
      peroxide H(2)O(2)-induced apoptosis of HL-60 human leukemia cells. The purpose of
      this study was to investigate the molecular mechanism(s) of MPO-mediated
      apoptosis, in particular caspase-3 activation, and to determine the effects of
      the antioxidants ascorbate and (dihydro)lipoic acid. Incubation of HL-60 cells (1
      x 10(6) cells/ml media) with H(2)O(2) (0-200 microM) resulted in dose-dependent
      stimulation of caspase-3 activity, DNA fragmentation, and morphological changes
      associated with apoptosis. Caspase-3 activity, DNA fragmentation and apoptosis
      were maximal at approximately 50 microM H(2)O(2). Pre-incubation of the cells
      with the MPO-specific inhibitor 4-aminobenzoic acid hydrazide (ABAH) and the heme
      enzyme inhibitor 3-aminotriazole (100 microM each) resulted in complete and
      partial inhibition, respectively, of intracellular MPO, caspase-3 activity, and
      apoptosis following addition of 50 microM H(2)O(2). Enhancement of cellular
      antioxidant status by pre-incubation of the cells with dehydro-ascorbic acid and
      lipoic acid, which are reduced intracellularly to ascorbate and dihydrolipoic
      acid, respectively, afforded protection against caspase-3 activation and
      apoptosis following addition of H(2)O(2). Addition of high concentrations of
      H(2)O(2) (200 microM) to cells pre-incubated with lipoic acid, however, resulted
      in cytotoxicity. Overall, our data indicate that MPO-derived oxidants, rather
      than H(2)O(2) itself, are involved in caspase-3 activation and apoptosis in HL-60
      cells, and the antioxidants ascorbate and (dihydro)lipoic acid inhibit caspase-3
      activation and apoptosis in these cells, likely via scavenging the MPO-derived
      oxidants.

PMID- 11981456
TI  - The Haber-Weiss cycle -- 70 years later: an alternative view.
AB  - In a recent review published in this journal,(1) Koppenol traced the history of
      the Fenton reaction and of the catalytic decomposition of H(2)O(2) by iron salts.
      If his purpose was to shed light on current understanding of related chemistry in
      biological systems, he failed. Moreover, he managed to sow confusion by
      inaccurate reporting of the work of others. What follows is an attempt to point
      out these shortcomings and thus to clarify the situation.

PMID- 11981458
TI  - [Failure of Helicobacter pylori eradication: causal factors and second line
      treatment].

PMID- 11981459
TI  - [Peritoneal carcinomatosis. Surgical treatment, peritonectomy and intraperitoneal
      chemohyperthermia].

PMID- 11981460
TI  - Failure of Helicobacter pylori eradication: is poor compliance the main cause?
AB  - OBJECTIVE: The aim of the study was to evaluate whether poor compliance can be
      considered as the main cause of the low Helicobacter pylori (H. pylori)
      eradication rate observed in an ambulatory population. METHODS: Seventy-eight
      patients with non-ulcer dyspepsia or gastroduodenal ulcer in whom H. pylori
      infection was confirmed by urease Clo-test and histology or bacterial culture,
      received a 1-week triple therapy comprising lansoprazole 30 mg b.d., amoxicillin
      1000 mg b.d. and clarithromycin 500 mg b.d. Compliance was assessed using MEMS(R)
      containers (Medication Event Monitoring System) which recorded time of medicines
      consumption. RESULTS: The overall H. pylori eradication rate was 65.4% (95% CI:
      54.8-76.0%) (intention to treat). Sixty-nine subjects (88.5%) consumed greater
      than 85% of doses and were considered as "good compliers". The major reason
      listed by the nine remaining patients for stopping treatment prematurely was side
      effects. In the population categorised as "good compliers", H. pylori eradication
      rate was 69.6% (95% CI: 58.7-80.5%) (per protocol) indicating that compliance
      could not be considered as the sole reason for treatment failure. Bacterial
      culture in a subset of 30 patients further showed a H. pylori eradication rate of
      73.9% (95% CI: 55.7-92.1%) in "good compliers" with a clarithromycin-sensitive H.
      pylori strain. On multivariate analysis, H. pylori eradication was inversely
      associated with poor compliance (P=0.029). Presence of a gastroduodenal ulcer,
      age, gender and smoking habit did not differ significantly between the eradicated
      and noneradicated groups. CONCLUSION: Although poor compliance and bacterial
      resistance were important factors in determining treatment success in our
      population, they could only explain 40% of failures suggesting that other factors
      must be involved.

PMID- 11981461
TI  - [Inter-observer agreement on histological diagnosis of colorectal polyps: the
      APACC study].
AB  - INTRODUCTION: Adenomas are considered as precursors of colorectal
      adenocarcinomas. After polypectomy, surveillance depends on the histological
      analysis of the excised polyps. The aim of the study was to evaluate the
      reproducibility of the histological diagnosis performed by pathologists from
      participating centers in the APACC study. Their interpretations were compared to
      those of the study's consensual diagnosis performed by two reference
      pathologists. METHODS: The agreement proportion and the concordance coefficient
      (kappa) were estimated for 326 polyps obtained from the first 148 patients
      included. RESULTS: A concordant diagnosis for the adenomatous nature was shown
      for 246 of the 255 adenomas (96%). The diagnosis of both the histological type
      and the degree of dysplasia was concordant for only 92 of the 255 adenomas (36%).
      Kappa values were 0.67 for the adenomatous nature, 0.46 for the histological
      types, and 0.26 for the degree of dysplasia. CONCLUSION: A high degree of
      agreement was obtained for the diagnosis of the adenomatous nature. By contrast,
      high variations were observed for the interpretations of the histological type
      and the degree of dysplasia.

PMID- 11981462
TI  - [Yield of colonoscopy by indication and consequences for colorectal polyp and
      cancer screening: a prospective survey in Isere, France].
AB  - AIM: The aim of this study was to determine yields of colonoscopy by indication,
      especially after a positive Hemoccult test, in the Isere area in southeastern
      France where a mass screening campaign for colorectal cancer using the Hemoccult
      test was conducted in women aged 50 to 69 years. METHOD: This prospective survey
      was conducted with the participation of all gastroenterologists in the Isere
      department. Information about indications of all colonoscopies performed and
      their results were collected. RESULTS: The study involved 1,779 colonoscopies
      performed for: digestive symptoms (40%), surveillance of colon disease (22%),
      hematochezia (18%), a family history of colon cancer (10%), anemia, poor general
      condition or metastasis (4%), and a positive test for blood in the stool (3%).
      The presence of a pathological colonic condition was significantly related to age
      (11% of cancers or large polyps after 50 years compared to 3% before), sex (10%
      of the women with lesions and 15% of the men) and the reason for prescription:
      after the age 50 a cancer or a large polyp was found in 27% of the cases if the
      colonoscopy was performed for anemia, metastasis or poor general condition, 21%
      for hematochezia, 20% for a positive test, 8% for digestive symptoms, and 2%
      because of a family history. CONCLUSION: Positive Hemoccult tests represent only
      a small part of the indications for colonoscopies performed in the Isere
      department. However, the screening program should be extended to develop its use
      given its yield which is equivalent to that of hematochezia and much higher than
      that of digestive symptoms or family history.

PMID- 11981464
TI  - [Synopsis: gastrointestinal lymphomas].

PMID- 11981465
TI  - [Comment on case report: gastric lymphoma disclosed by hematemesis].

PMID- 11981466
TI  - [Interview: questions to professor Jean-Claude Rambaud].

PMID- 11981468
TI  - [Osteoporosis and chronic liver disease].

PMID- 11981469
TI  - [Angiotensin II receptor antagonists and portal hypertension].

PMID- 11981470
TI  - [Seroprevalence of hepatitis A and cost evaluation of different vaccination
      strategies against hepatitis A virus in patients with chronic hepatitis C in
      France].
AB  - OBJECTIVES: To prospectively determine the prevalence of total hepatitis virus A
      antibodies in patients with chronic hepatitis C and to evaluate the direct costs
      of several vaccination strategies against hepatitis A virus in these patients.
      METHODS: From April 1 to July the 31 1998, 219 patients with hepatitis C virus
      antibodies underwent a systematic testing for total hepatitis virus A antibodies
      (MEIA-AXSYM, Abbott laboratories). The prevalence of hepatitis A virus antibodies
      was evaluated according to age and suspected way of hepatitis C contamination.
      This prevalence has been compared to that in individuals undergoing a check-up
      provided by the national health insurance system stratified by age. Direct costs
      of 2 vaccination strategies "A" and "B" were evaluated according to age (<40 vs >
      40 years) and number of vaccine doses (1 or 2). "A" strategy included the
      systematic vaccination of all patients without determining the presence of total
      hepatitis A antibodies. "B" strategy included testing for total hepatitis A
      antibodies and vaccination of seronegative patients. The costs of these two
      strategies (A and B) were calculated with one and two vaccine doses. RESULTS: The
      prevalence of total hepatitis A antibodies was 76% in the entire population. It
      increased after the age of 35 and was statistically higher in patients who were
      older than 40 than in patients younger than 40. This prevalence was not
      significantly different from that in individuals who underwent a check-up
      provided by the national health insurance system stratified according to age. "B"
      strategy with 2 vaccine doses was less expensive that A strategy in the whole
      population and in patients younger than 40. This strategy was less expensive with
      1 vaccine dose except in patients who had recently screened positive for
      hepatitis C antibodies younger than 40 when it induced an increased in direct
      cost due to the low prevalence of total hepatitis A antibodies in these patients.
      CONCLUSIONS: In patients with hepatitis C antibodies with a high prevalence of
      total hepatitis A antibodies, testing for the prevalence of these antibodies
      before vaccination decreases the direct cost of this vaccination.

PMID- 11981471
TI  - [Factors related to screening of hepatitis C virus in general medicine].
AB  - Despite the high prevalence of hepatitis C in France ( approximately 1.2%), a
      large proportion of people infected with hepatitis C virus (HCV) are not known
      aware of their status. The objective of this study was to investigate the factors
      related to screening in general medicine. MATERIAL AND METHODS: Three hundred and
      one general practitioners were interviewed by phone in South-Eastern France about
      their HCV screening practices, knowledge of the epidemic, of the natural course
      of the disease, and opinions about health care for people infected with HCV.
      RESULTS: While general practitioners often offered HCV screening to intravenous
      drug users, screening for people who had received blood transfusion, and
      identification of risk factors among patients were not satisfactory. Multivariate
      analysis showed that certain characteristics in general practitioners were
      negatively and independently related to the frequency of HCV screening,
      especially: general practitioners older than 40 (odds-ratio: 3.12), general
      practitioners who did not care for intravenous drug users (odds-ratio: 2.24) and
      did not prescribe human immunodeficiency virus tests (odds-ratio: 5.55). Other
      characteristics such as awareness of the course of hepatitis C and health care
      were also associated with HCV screening. Conversely knowledge of the size of the
      epidemic was not related to better HCV screening practices. CONCLUSION: Our study
      shows that knowledge about the size of the epidemic and the natural history of
      hepatitis C, HCV screening practices and investigation of risk factors among
      patients are not satisfactory among South-eastern French general practitioners.
      Although HCV screening and health care must be improved among intravenous drug
      users, hepatitis C should not be considered as a disease of injecting drug users
      only by general practitioners and the population. Efforts should be made so that
      hepatitis C is recognized as a global public health issue, and training of
      general practitioners should be improved to investigate risk factors and offer
      HCV screening instead of merely dramatizing the situation.

PMID- 11981472
TI  - [Prevention and treatment of hepatitis B virus infection after liver
      transplantation].

PMID- 11981473
TI  - [Perforated juxta-papillary duodenal diverticula: two cases].
AB  - Perforation of juxta-ampullary duodenal diverticula, occurring spontaneously or
      after abdominal trauma, is a severe condition. Diagnosis is difficult to
      establish and is based on tomodensitometry, which is the most reliable diagnostic
      tool. Treatment consists in diverticulectomy that can be associated with drainage
      of the duodenum or anastomosis between digestive and biliary tract. We report two
      cases of perforated juxta-ampullary duodenal diverticula. Perforation was
      spontaneous in one case and complicated a blunt abdominal trauma in the other
      case.

PMID- 11981474
TI  - [Aerobilia: a rare consequence of anaerobic acute cholecystitis: a case report].
AB  - Acute acalculous cholecystitis is rare in non critically ill or postoperative
      patients. We report a case of acute acalculous cholecystitis with secondary bile
      infection with Clostridium perfringens. Ultrasound and tomodensitometry revealed
      diffuse aerobilia. The germ in this case report is atypical and contrasts with
      the very discrete clinical findings. Aerobilia, secondary to the development of
      bacteria in the biliary tract falsely suggested a bilio-digestive fistula.
      Treatment included a simple cholecystectomy associated with 7 days of
      antibiotherapy.

PMID- 11981475
TI  - [Non-steroidal antiinflammatory drug-related duodenal diaphragm treated by
      diathermic endoscopic incision].

PMID- 11981476
TI  - [Vesiculo-pustular eruption and Crohn's disease].

PMID- 11981477
TI  - [Sweet's syndrome and erythema nodosum associated with Crohn's disease treated by
      infliximab].

PMID- 11981478
TI  - [Sclerosing cholangitis secondary to an accidental injection of chlorhexidine
      (Mercryl(R)) into the biliary tract: a case report].

PMID- 11981479
TI  - [Splenic infarction associated with Zolmitriptan use].

PMID- 11981480
TI  - [Mycophenolate mofetil induced acute hepatitis].

PMID- 11981482
TI  - [LH Day: floodlights on a forgotten compound].

PMID- 11981483
TI  - [LH receptors: follicle and endometrium].
AB  - LH-receptors are widely distributed in the human body. The talk focussed on
      ovarian and endometrial receptors. Ovarian LH receptors Uterine LH receptors In
      conclusion, LH and hCG should no longer be viewed as only gonadal regulating
      hormones. They have multiple targets in the body. Better understanding of
      nonclassical actions could lead to novel therapeutic applications of hCG such as
      prevention of threatened and habitual abortions, preterm labor, etc.

PMID- 11981484
TI  - [Role of LH in folliculogenisis during the menstrual cycle].
AB  - LH participates, with FSH, in normal follicle growth. LH and the ovarian follicle
      LH and the egg Implication of LH in oocyte modification via paracrine mediation
      and via the action of somatic cells following stimulation of the receptors
      present on the granulosa cells. LH and ovulation Control of ovulation by the LH
      peak inducing, about 36 hours later, rupture of the follicle, secretion of
      progesterone, and formation of the corpus luteum. Activation of LH by a pro
      inflammatory cascade during follicle rupture and, in response, an anti
      inflammatory cascade leading to repair of the ovary surface.

PMID- 11981485
TI  - [Polycystic ovaries in 2001: physiology and treatment].
AB  - Clinical characteristics of PCOS Syndrome Two fundamental characteristics:
      hyperandrogenism and anovulation which lead to hirsutism and oligo-or amenorrhea.
      Other features include obesity, acanthosis nigricans, and metabolic disruption
      (insulin resistance with hyperinsulinemia, glucose intolerance, or type II
      diabetes mellitus). Complementary tests Serum testosterone and DHEA-S levels: to
      exclude androgen-producing tumors. Serum 17-hydroxyprogesterone level: to exclude
      congenital adrenal hyperplasia, 21-hydroxylase deficiency. Ultrasound: increased
      size of the ovaries and central stroma with presence of peripheral follicular
      cysts (8-10) measuring about 8 mm in diameter. Pathophysiology Therapeutic
      approaches Therapeutic approaches

PMID- 11981486
TI  - [Role of LH in ovarian stimulation: present and future].
AB  - Contribution of LH to ovarian stimulation, distinguishing treatment of
      anovulation and ovarian stimulation with the objective of IVF. LH and ovarian
      dysfunction LH furnishes the androgen substrate necessary for FSH for estrogen
      synthesis, but excess LH is a less reliable index than free androgen level to
      predict the absence of response to ovarian stimulation. LH and ovarian
      stimulation

PMID- 11981487
TI  - [LH and gamete quality].
AB  - Potential contribution of LH to controlled ovarian stimulation in the final
      maturation of the oocyte and in preparation of the endometrium. LH and oocyte
      maturation LH and implantation Implantation rate variable but increased with
      LH/hCG, probably due to fewer abortions. CONCLUSION: Is LH/hCG is an
      immunomodulator but it may have a positive impact on the quality of the gametes
      through cytoplasmic improvement.

PMID- 11981488
TI  - [LH and GnRH antagonists].
AB  - New GnRH antagonists are available in clinical practice. The different studies
      have confirmed the efficacy of these antagonists in preventing the LH surge. Two
      protocols have been described: in the multiple dose regimens, small doses of
      antagonist (0.25 mg) are injected starting on stimulation day 5 or 6 until hCG.
      In the single dose protocol, one injection of a larger dose (3 mg) is proposed in
      the late follicular phase. The remaining levels of endogenous LH appears to be
      sufficient in the multiple doses protocol. In the single an estradiol drop is
      observed in some patient following the 3 mg injection of Cetrorelix. This drop is
      related to the LH decrease. Its adverse effect on IVF results is not
      demonstrated.

PMID- 11981489
TI  - [LH and triggered ovulation].
AB  - Actions of the LH peak Mechanisms of the LH-peak triggered ovulation Interest of
      reproducing the LH peak in stimulated cycles

PMID- 11981490
TI  - [Hepatic imaging and radiologists: keep your post in the battle!].

PMID- 11981491
TI  - [Surgical anatomy of the liver: what you need to know].
AB  - A precise knowledge of arterial, portal, hepatic and biliary anatomical
      variations is mandatory when a liver surgery is planned. However, only certain
      variations must be searched when a precise intervention is planned. The main
      liver resection and biliary interventions will be precised. Related anatomical
      variations will be precised.

PMID- 11981492
TI  - [Biliary and vascular anatomy of the liver].
AB  - This paper is a review of the anatomy of the bile ducts and the vascular anatomy
      of the liver. This anatomy is subject of numerous variations which can be
      explained by the embryology of the liver and its vessels. The perfect knowledge
      of this anatomy is useful for an accurate interpretation of the conventional and
      slice imaging techniques of the liver. It is also of major importance for an
      appropriate management of all kinds of hepatic vascular and biliary percutaneous
      procedures.

PMID- 11981493
TI  - [Liver anatomy: echography and Doppler].
AB  - Ultrasonography is an excellent tool for the study of the anatomy of the human
      liver. This article shows, with the help of sonographic views along the long axis
      of portal and hepatic veins, and the different landmarks of the liver, how to
      delineate the eight segments of the liver. Doppler examination allows
      indentification of the portal veins and the hepatic arteries in the portal triad.

PMID- 11981494
TI  - [Liver anatomy: CT and MRI].
AB  - Computed tomography and magnetic resonance imaging are widely used tools to
      appreciate liver anatomy. Vascular and segmental anatomy are adequately
      appreciated with CT, while biliary anatomy is mainly seen with MR imaging. Basic
      principles of techniques and anatomical landmarks will be detailed.

PMID- 11981495
TI  - [Liver and vascular abnormalities].
AB  - The liver is a parenchyma which contains many vessels. They are composed of two
      inflow vessels: the portal vein and the hepatic artery, and one outflow system
      represented by the hepatic veins. We will see in the chapter most of the
      abnormalities and their consequences due to decrease or an increase of the blood
      flow of these vessels. Many illustrations will be provided with a special focus
      on CT findings with multiphasic images.

PMID- 11981496
TI  - [Radiological differential diagnosis of focal liver lesions with anatomo
      pathological correlations].
AB  - Starting from the macroscopic, microscopic and circulatory characteristics of
      focal liver lesions, we aimed at assessing the possibilities and the limits of
      their radiological differential diagnosis. We compared the normal hepatic
      parenchyma (in terms of: general morphology, cellularity, necrosis, macro- and
      micro-circulation) and the lesions, assessed following the radiological features
      of echoreflectivity, RX density, contrast dynamics and specific contrast uptake.
      The association of morphologic and dynamic features can sometimes lead to an
      excellent diagnostic specificity (by example: angioma); in other fields,
      interesting results are noted, but the limits of every modality require further
      evaluation. This study applies to the following focal lesions: angioma, focal
      hyperplasia, adenoma, regeneration nodule, hepatocarcinoma, metastasis.

PMID- 11981497
TI  - [Fibrous tissue(s): a key for lesion characterization in digestive diseases].
AB  - Fibrosis is one of the hallmarks of inflammatory and repair processes in
      pathology. Various exogenous and endogenous stimuli, including tumor development,
      can induce inflammatory reactions. During the post-equilibrium phase after IV
      injection of non specific contrast media, CT and/or MR allow the study of these
      inflammatory answers to tumoral or infectious processes. Delayed enhancement of
      collagenic fibrous tissue during the late post-equilibrium phase is an essential
      complementary data in the characterization of many liver lesions: cirrhosis,
      cholangiocarcinoma, focal nodular hyperplasia, fibrous metastasis. but also for
      the differential diagnosis of pancreatic diseases (groove pancreatitis vs ductal
      adenocarcinoma) or of gastro-intestinal diseases (gastric adenocarcinoma vs
      lymphoma, mechanical complication vs inflammatory bouts of ileal Crohn's
      disease).

PMID- 11981498
TI  - [When should surgical lung biopsy be proposed for patients with diffuse
      infiltrating lung disease?].

PMID- 11981499
TI  - [Biological criteria for distinguishing exudative and transudative pleural
      effusions. Usefulness in a general hospital].
AB  - The first step in the diagnosis of a pleural effusion is to determine the
      exudative or transudative nature of the fluid. The purpose of this work was to
      compare different biological criteria commonly used in clinical practice. Among
      118 pleural effusion fluids studied, 24.6% were exudates and 75.6% were
      transudates. The different parameters studied were Light criteria, Costa
      criteria, protein content, cholesterol content, and lactate dehydrogenase
      activity in the pleural fluid. The results showed that the Light criteria enabled
      classing all the fluids as exudates or transudates. We were also able to
      demonstrate that simple assay of lactate dehydrogenase activity in the pleural
      fluid gave comparable results, avoiding the need for further blood samples.

PMID- 11981500
TI  - [Treatment of tracheobronchomegaly with an Ultraflex prosthesis. A case report].
AB  - Tracheobronchomegaly is defined as a dilatation of the trachea and the large
      bronchi. It may occur as a familial condition or in association with a connective
      tissue disease, e.g. Ehlers-Danlos syndrome. Tracheobronchomegaly occurs late in
      adults. The predominant symptoms are bronchial irritation and recurrent
      bronchopulmonary infections (because of ineffective cough). Diagnosis is provided
      by thoracic imaging, particularly computed tomography that enables measuring the
      precise diameter of the trachea. We report the case of one patient with
      tracheobronchomegaly who was greatly improved after implantation of Ultraflex
      tracheobronchial prostheses.

PMID- 11981501
TI  - [Interstitial lung disease in a patient given gemcitabine].
AB  - The differential diagnosis between infectious complications and tumor progression
      is sometimes difficult in patients given cytotoxic drugs. We report a case of
      diffuse interstitial lung disease induced by gemcitabine, a new agent used for
      the treatment of advanced-stage non-small-cell lung cancer.

PMID- 11981502
TI  - [Bronchial atresia. A case report].
AB  - Bronchial atresia with mucocele and focal hyperinflation of the lung is a rare
      anomaly. We report the observation of a 12-year-old girl which presented a right
      hilar opacity on chest X-ray. The thoracic computed tomography identified an
      atretic segmental bronchus of the middle lobe with mucocele and focal
      hyperinflation of the lung. Bronchial endoscopy ruled out any acquired etiology
      of bronchial obstruction. The definitive diagnosis was bronchial atresia with
      mucocele and focal hyperinflation of the lung. This uncommon malformation is
      usually a radiological description. Eighty-four cases were collected in the main
      series in 1989. Nowadays, about 12 new cases have been published.

PMID- 11981503
TI  - [Metastatic benign leiomyoma in a 46-year-old woman].
AB  - Chest X-ray in a 46-year-old woman with a history of hysterectomy for a uterine
      mass revealed a nodular opacity measuring 3 cm. Computed tomography identified 3
      other nodules. Histology examination of the lung lesions identified the same
      configuration as that of the hysterectomy specimen performed two years earlier:
      benign metastatic leiomyoma. Approximately 40 cases have been reported in the
      literature.

PMID- 11981504
TI  - [Solitary fibrous thoracic tumor: a rare tumor with unpredictable course].
AB  - A 68-year-old woman presented chest pain and exercise-induced dypnea for one
      year. Diagnosis was a thoracic solitary fibrous tumor. These tumors are very
      rare. Clinical outcome is generally good except in 13% of the cases with a
      malignant component. Complete surgical resection is required.

PMID- 11981505
TI  - [Multifocal tuberculosis: fatal outcome due to toxic drug reactions].
AB  - We report a case of multifocal tuberculosis with the following features: - skin
      involvement with multiple gommes disseminated on the left upper limb, the left
      flank, the right hypocondrium, and the right leg; - nodal involvement including
      the left supraclavicular, left axillary, right laterotracheal, pre and
      subcarineal, ceoeliomesenteric, and liver hilus nodes; splenic involvement; right
      pleural involvement; - spondylodiscitis of T11-T12 and of the head of the right
      fibula; - peritoneal involvement leading to ascitis; - multi-organ involvement.
      This 43-year-old woman had not particular history: no diabetes, no renal failure,
      no long-term corticosteroid treatment, no immunosuppressor treatment, negative
      HIV-1 and HIV-2 serology. Treatment with anti-tuberculosis agents led to severe
      drug reactions causing death due to hepatic encephalitis.

PMID- 11981506
TI  - [A worm in the apple].

PMID- 11981507
TI  - [Exploration of a hemoptoic expectoration].

PMID- 11981509
TI  - Advice for travelers.

PMID- 11981510
TI  - Valdecoxib (Bextra)--a new cox-2 inhibitor.

PMID- 11981511
TI  - Pantoprazole IV (Protonix IV).

PMID- 11981513
TI  - Trauma Centres: what role is played by the anesthesiologist-resuscitator in
      Italy?

PMID- 11981514
TI  - Daily classification of complexity/level of intensive medical care. Does it allow
      the monitoring of the managerial process in ICU?

PMID- 11981515
TI  - [The use of laryngeal mask airway in esophagogastroduodenoscopy in children].
AB  - BACKGROUND: The use of laryngeal mask airway (LMA) for inducing and maintaining
      sedation during EGDS has never been reported in the literature but for a brief
      letter written by Gajraj in 1996. This study proposes the use of sevoflurane
      administered through LMA. METHODS: At the Pediatric Clinic of the University of
      Rome "La Sapienza" 80 children un-derwent EGDS. After premedication, immediate 8%
      sevoflurane and 60/40% N2O/O2 induction was delivered. Concentration of
      sevoflurane was reduced to 1% for maintaining general anesthesia. Heart rate
      (HR), systemic blood pressure (SBP), respiratory rate (RR), EtCO2 and SpO2 were
      not invasively monitored. Time for induction, time for emergence as well as
      complications, if any, were also evaluated. RESULTS: The monitored parameters did
      not show any significant changes. The time for loss of eyelash reflex and the
      time for end of induction were of 121+/-15 sec. 3.5+/-1.3 min respectively. The
      time for emergence was 3.4+/-1.8 min. Only minor complications were reported.
      CONCLUSIONS: The results obtained show that the use of LMA associated to
      sevoflurane as single inhaling agent can be a valid technique for EGDS in
      pediatric patients.

PMID- 11981516
TI  - [Epidural analgesia during labor: intermittent bolus or patient controlled
      administration?].
AB  - BACKGROUND: The aim of the study was to compare efficacy and side effects
      produced by two techniques of epidural analgesia during labor: intermittent bolus
      and patient-controlled epidural analgesia. METHODS: Eighty parturients were
      enrolled in this study: forty received intermittent bolus analgesia (first bolus:
      20 mg of ropivacaine 0.1% + 10 gamma of sufentanil, next bolus: 10 mg of
      ropivacaine 0.1% during the first 4 hours, and then 10 mg of ropivacaine 0.1% +
      2.5 gamma of sufentanil each time they complained of pain), and forty parturients
      received PCEA (starting with a bolus of 20 mg ropivacaine 0.1% + 10 gamma
      sufentanil, followed by administration with a pump programmed to deliver a
      continuous background infusion of ropivacaine 0,1% + 0.25 gamma/ml of sufentanil
      at 5 ml/h and 5 ml patient-triggered boluses with a 15 min lock-out interval;
      insufficient analgesia was treated by extra boluses of the same ropivacaine
      solution). In each group the efficacy of the analgesia (verbal numerical pain
      scores, amount of local anesthetics consumption), labor duration, side effects
      and patient satisfaction have been studied. RESULTS: There were no differences
      between the two different epidural techniques. CONCLUSIONS: This regimen of PCEA
      proves a viable and safe alternative for epidural analgesia during labor.

PMID- 11981517
TI  - [The Fantoni translaryngeal tracheostomy: perioperative complications In a series
      of 220 consecutive patients].
AB  - BACKGROUND: To evaluate problems arisen du-ring Fantoni translaryngeal
      tracheostomy (TLT). METHODS:  SETTING: intensive care unit. PATIENTS: 220
      patients (aged from 18 to 87). EXCLUSION CRITERIA: coagulopathy, difficult
      intubation, local infections, previous neck surgery, suspected cervical spine
      lesion, severe hypoxemia, hemodynamic instability, patients close to be
      discharged from ICU. Operation: TLT was performed in general anesthesia, using
      the technique described by Fantoni in 206 cases; in the other 14 cases changes
      were made. RESULTS: Perioperative clinical complications were separated from
      instrumental problems. Clinical complications were 28 (12.7% of TLT): 20 (9.1% of
      total TLT, 71.4% of total complications) were considered minor and ascribed to
      medical staff training; among these the complete drawing of the cannula and the
      difficulty in pushing it in trachea. Eight complications (3.6% of TLT, 28.6% of
      total complications) were considered major; they were: the impossibility to place
      the cannula in trachea, the displacement of the prothesis in the peritracheal
      tissue, the rupture of tracheal ring, the bleeding and the infection of
      tracheostomy, the dental uprooting. Among instrumental problems, the faulty
      closure of the ring nut, the overdimension of rigid tracheoscope, and the
      difficult change of the cannula were observed. CONCLUSIONS: With expert medical
      staff, this technique is effective and safe, with a low rate of complications.
      Major complications were rare, and occurred in spite of patients selection, often
      needing changing of TLT in surgical tracheostomy.

PMID- 11981518
TI  - [Validation of the Italian version of the "Neuropathic Pain Scale" and its
      clinical applications].
AB  - BACKGROUND: The Neuropathic Pain Scale is the first specific tool to measure and
      analyse pain due to a lesion in the nervous system; this kind of pain is usually
      difficult to describe for the patient because it is characterized by unusual
      qualities. Aim of this study is to evaluate a possible relation between pain
      descriptions and underlying pathogenetic mechanisms. METHODS: The Italian version
      of the Neuropathic Pain Scale has been administered to 145 patients with
      neuropathic pain due to chronic radiculopathy, diabetic neuropathy, post
      traumatic neuropathy, Complex Regional Pain Syndrome or postherpetic neuralgia.
      As it has been done in Galer's study, the predictive validity and the items'
      correlation have been evaluated; moreover, the structure validity of the scale
      has been studied. RESULTS: Pain values were high in all pain syndromes with the
      prevalence of certain items in particular pathologies. The correlation of some
      items with "deep pain" and others with "superficial pain" was also observed.
      CONCLUSIONS: The results have confirmed the statistical validity of the Italian
      version of the scale; they also pointed out the usefulness of the scale to
      distinguish between superficial pain, typical of neuropathic pain, and deep pain,
      typical of somatic pain.

PMID- 11981519
TI  - New antidepressants in the treatment of neuropathic pain. A review.
AB  - Before 1980s, tricyclics (TCAs) were considered, between antidepressants, the
      standard in the treatment of different kinds of neuropathic pain, for their
      action on noradrenergic and serotoninergic pathways, thought the high incidence
      of side effects. In 1980s a new class of antidepressants has been introduced, the
      selective serotonin reuptake inhibitors (SSRI). We reviewed some publications,
      including trials comparing SSRIs with TCAs in pain management. The available
      literature did not show an effective superiority of the former on the latter,
      though improved side-effect profile. Recently new antidepressants were introduced
      in the clinical use, with a significant reduction in side effects and equivalent
      efficacy on mood disorders. These new drugs may be classified in three
      categories: Serotonin and Noradrenergic Reuptake Inhibitors (SNaRI), like
      venlafaxine and nefazodone; Noradrenergic and Specific Serotoninergic
      Antidepressants (NaSSA), like mirtazapine, and Noradrenaline Reuptake Inhibitors
      (NaRI), like reboxetine. In this review we present the available publications of
      their application in the treatment of neuropathic pain. Venlafaxine (SNaRI), the
      most investigated of these new drugs, was shown to be effective in the treatment
      of different kinds of pain, with side-effects profile significantly better than
      TCAs. The other new antidepressants have been less extensively studied, thus only
      anecdotal therapeutic results and experimental works have been found and
      reported. Existing data are surely insufficient to conclude which of these new
      classes of drugs has the best clinical profile and can be more effective in the
      treatment of neuropathic pain, but the lower incidence of side effects should be
      considered. Further evidence-based research in the safety and efficacy of these
      promising agents in pain relief, is warranted.

PMID- 11981520
TI  - [Theoretical bases of a cardio-synchronised jet injection system into the vena
      cava].
AB  - Aim of this paper is to present a procedure aimed at raising the flow rate in the
      vena cava. To this purpose some fluid is injected at high speed in the vessel,
      accelerating the flow and dragging the stagnating flow upstream the catheter. In
      order to raise the efficiency of the system and to avoid damage to heart valves,
      the injection is synchronised with the diastole. A prototype of an injection
      system has been designed and built, in order to reach these goals. The injection
      times are controlled by the electrocardiogram track of the patient, in such a way
      that the maximum flow rate occurs when the tricuspid valve is open. A "dragging
      effect" index, that is the ratio between overall flow rate induced by any
      injection (injected flux plus dragged flux) and injected flux flow rate has been
      evaluated, both theoretically and experimentally. An experimental model of the
      lower vena cava has been built and used to measure the velocity profile in the
      vessel. The dragging effect at the confluence between the two iliac and the vena
      cava has been verified. By making the catheter sections smaller and/or raising
      the feeding pressure it is possible to have the injection of small volumes at
      high speed, capable of moving the blood in the vena cava with a minor
      contribution of external fluid, thus reducing risks of volume overload and
      overdiluition of blood.

PMID- 11981521
TI  - Trauma centers.

PMID- 11981522
TI  - [Prevention of respiratory syncytial virus infections].

PMID- 11981523
TI  - Children, sleep, and behavior: a complex association.
AB  - Pediatric sleep physiology begins with development of the sleep/wake cycle, and
      the origins of active versus quiet sleep. The 24-hour circadian cycle becomes
      established at 3-6 months. Sleep disorders during infancy commonly include mild,
      usually self-limited conditions such as sleep-onset association disorder,
      excessive nighttime feedings, and poor limit-setting. These require behavioral
      management to avoid long-term deleterious sleep habits. In contrast, other sleep
      disorders are more ominous, including SIDS, central congenital hypoventilation
      syndrome, and sleep apnea. Childhood is generally considered the golden age of
      sleep, with brief latency to sleep onset, high efficiency, and easy awakening.
      Yet parasomnias, psychological factors, and sleep disturbances associated with
      common disorders such as ADHD disrupt the idealistic notion of childhood being a
      period of unfettered sleep. Adolescents have sleep requirements similar to
      adults, posing a challenge for them to adapt to school schedules and increasingly
      demanding lifestyles. Narcolepsy, usually diagnosed in adolescence or early
      adulthood, is a lifelong sleep disorder and has led to the identification of the
      hypocretin/orexin neurotransmitter system. Research advances in the complex
      interrelationships between developmental neurobiology, sleep disorders and
      behavior will lead to an enhanced understanding of the pathophysiology of sleep
      problems and lead to novel therapeutic strategies for sleep disturbances in
      children.

PMID- 11981524
TI  - Physical activity and bone development during childhood and adolescence.
      Implications for the prevention of osteoporosis.
AB  - Osteoporotic fractures are a debilitating and a frequently fatal health problem
      for older adults. A growing body of evidence indicates that osteoporosis has its
      origin in early life and that the level of development of bone mass during
      childhood and adolescence strongly influences the risk for osteoporotic
      fractures. The development of osteoporosis results from an interaction between 1)
      bone mass accrual via growth, remodeling, and modeling during childhood and
      adolescence and 2) the maintenance of bone mass (primarily via remodeling) during
      adulthood. Peak bone mass which occurs at the conclusion of growth may be the
      most important factor for preventing osteoporosis since as much bone is accrued
      during the adolescent years as most individuals will lose during all of adult
      life. In this review, I examine the contribution of physical activity as an
      important behavioral determinant of children's bone development, particularly of
      peak bone mass. Since it is a behavior, physical activity is a potentially
      modifiable determinant of peak bone mass; therefore, understanding activity's
      impact on bone health is central to developing primary prevention strategies for
      osteoporosis.

PMID- 11981525
TI  - Integration of statistical theory and practical clinical expertise. Polymerase
      chain reaction testing of the HIV-exposed infant.
AB  - Testing of the human immunodeficiency virus (HIV)-exposed infant has improved
      markedly over the past decade. Polymerase chain reaction (PCR) technology has
      made accurate diagnosis possible by 4 months of age and improved sensitivity and
      specificity of PCR testing has obviated the need for serologic follow-up for most
      HIV-exposed infants. Clinicians may use PCR testing and simple statistical theory
      to develop a rational algorithm for diagnosis of HIV-exposed infants. Physicians
      should determine whether the infant is at low, moderate, or high risk for
      acquiring HIV. After risk-stratification the physician may proceed with 2 PCR
      tests, 3 PCR tests, or PCR testing and serologic follow-up. Infants of mothers
      who are on highly active antiretroviral therapy (HAART) at delivery, whose
      mothers have a low or undetectable viral load at delivery, and who do not breast
      feed, should be considered low-risk. These low-risk infants should have 2 PCR
      tests, 1- and 4-months post partum. Infants whose mothers have an unknown or high
      viral load at delivery and who do not breast-feed should be considered moderate
      risk. These infants should have 3 negative PCR tests, 1 during the first month of
      life, 1 after the first month of life, and 1 after 4 months of life. Infants who
      breast-feed should be considered high-risk and require at least 3 negative PCR
      tests, PCR testing every 3 months until breast-feeding stops, and serologic
      follow-up. Any positive PCR test requires virologic confirmation and serologic
      follow-up.

PMID- 11981526
TI  - [The biological specificity and superiority of human milk. Scientific basis,
      guarantees and safety controls].
AB  - Scientific knowledge has demonstrated that breastfeeding is the ideal method of
      feeding and nurturing infants and has recognised breastfeeding as primary in
      achieving optimal infant health, growth and development. Human milk is species
      specific and offers a superior method of feeding. All other options differ
      markedly from it. Milk formulas are designed to mimic human milk as much as
      possible, but important compositional differences between human milk and formulas
      remain, and it is unlikely that this situation will change very soon, if ever.
      Thus, the breastfed infant remains the reference model against which all
      alternative feeding methods are measured, with regard to health, growth and
      development. Human milk has a dynamic nature and varies with time postpartum, but
      the variations of its composition with time of lactation match the changing needs
      of the growing infant. The role of the pediatrician is essential in promoting,
      protecting and supporting breastfeeding in the hospital, medical schools,
      individual practices and in the community. The purpose of this review is to
      describe and provide insight into the nutritional benefits, the contributions to
      host defence and the social and psychological benefits of maternal-infant bonding
      obtained by breastfeeding. This paper also summarises other substantial
      advantages obtained when infants are fed at the breast and describes the rare
      situations and medical reasons when human milk is not recommended, when
      alternative options should be considered, or when breastfeeding must be closely
      monitored. Early identification of those infants fed at the breast who have
      inadequate intakes is important, also to preserve breastfeeding.

PMID- 11981527
TI  - [Esophageal atresia with distal tracheo-esophageal fistula. Evolution of the
      treatment in the period of 1955-2000 at the Anna Meyer Children's Hospital of
      Florence].
AB  - BACKGROUND: Over the past decades the esophageal atresia (EA) has represented the
      greatest challenging malformation encountered by the pediatric surgeon. Since
      then, there have been considerable advancements in the treatment of EA. In this
      paper the experience at the "Anna Meyer Children's Hospital of Florence" in
      regards to the surgical treatment of the EA from 1955 to present day is reported,
      so that the analysis of the various medical and surgical choices followed by the
      authors and their predecessors in this long period, can be an important learning
      tool for the EA management. METHODS: From 1955 to 2000, 223 newborns affected by
      EA with tracheoesophageal fistula (TEF) have been operated on out of a total of
      250 cases of EA. Our experience has been subdivided into periods on the basis of
      homogeneous medical and surgical treatment adopted in that determined time. We
      have analyzed particularly the data of the last period 1995-2000, where there has
      been a well standardized protocol of treatment from the medical, surgical and
      intensive care points of view. RESULTS: The mortality rate has decreased from
      44.8 to 3.4% with a significant reduction (p<0.001) between the years 1979-1983
      and 1984-2000, due to the introduction of a perioperative treatment in the
      newborn intensive care unit. Moreover, a significant correlation (p<0.05) has
      been shown between low birthweight and associated malformations, two risk factors
      that however do not negatively influence the results of the treatment in the last
      period 1995-2000. CONCLUSIONS: A full integration between the surgeon and
      neonatologist is necessary in order to guarantee a good result. The risk
      connected to EA is not as much the surgical procedure as the presence or absence
      of associate malformations that are undetected in the prenatal diagnosis. It is
      suggested that, in order to further reduce the mortality and morbidity rate after
      EA correction, the number of prenatal diagnoses should be increased.

PMID- 11981528
TI  - [Assessment of eating disorders-related risk in a cohort of adolescents living in
      Northern Italy. Results from a multicenter study].
AB  - BACKGROUND: Clinical evidence and epidemiological research show an increasing
      number of subjects trying to become lean and reaching consequently harmful weight
      conditions. Aim of this paper is to assess the risk for eating disorders during
      adolescence. METHODS: In a multicentric study high school students of 5 different
      districts of Northern Italy have been asked to fill up anonymously the Italian
      version of the American YRBSS (Youth Risk Behaviour Surveillance System)
      questionnaire. For each school a section has been selected and between January
      and March 1999, students of every level have been involved. The data enrollected
      have been analysed using EpiInfo6. RESULTS: The study involved 4135 adolescents
      (57% girls and 43% boys) coming from 260 classes and 47 different schools. The
      proportion of boys perceiving themselves as overweight and underweight was the
      same (22%), while the proportion of girls considering themselves overweight
      raised up to 42%. The majority of the girls (53%) is trying to slim making use of
      physical activity (48%), diets (32%), vomiting (8%) and drugs (5%). CONCLUSIONS:
      Our data suggest that specific projects focusing on primary and secondary
      prevention of eating disorders should be considered for high schools. In
      addition, further studies are suggested to understand characteristics and
      behaviours related to eating disorders.

PMID- 11981529
TI  - Acute complicated sphenoiditis in childhood. Case report and literature review.
AB  - In ENT practice, acute uncomplicated sphenoiditis is rarely diagnosed: very often
      diagnosis is involved for multiform and unspecific symptomatology, such as to
      sham nervous, visual and upper respiratory tract diseases. Only a careful
      differential diagnostics and an instrumental investigation consents to realise
      quickly a specific treatment, avoiding some complications, still frequent. This
      case-report, underlines that the polyspecialists' co-operation is necessary to
      make a correct diagnosis, and to avert important and dangerous complications into
      shapes of sphenoiditis.

PMID- 11981530
TI  - [Neonatal vocal cord palsy. Clinical and therapeutical approaches].
AB  - Between 1998 and 2000, four newborns have been observed for laryngeal stridor
      occurred some hours after birth. Otorhinolaryngologic examinations, as well as
      cardiac, neuroradiologic and serologic investigations have been performed to
      formulate the diagnosis and verify the etiology. The fiberoptic laryngoscopy
      showed a bilateral paralysis of the vocal cord in two newborns, a monolateral
      paralysis of the left vocal cord in another and in the last one, instead, a
      bilateral cordal hypomobility. The follow-up performed till the age of one year
      showed a complete remission of the symptomatology in two newborns, respectively
      in the one with monolateral paralysis and in the other affected by hypomobility
      of the vocal cords; of the two newborns with bilateral paralysis, instead, one is
      dead because of Haemophilus Influenzae epiglottitis, three weeks after discharge
      without physicians' consensus, while in the other patient, affected by lobar
      holoprosencephaly, it was necessary to perform a tracheotomy because of a severe
      obstructive apnea. The lobar holoprosencephaly, is a cerebral malformation
      characterized by the partial separation of the cerebral hemispheres, and it is
      described for the first time associated with bilateral vocal cords paralysis.

PMID- 11981531
TI  - Early onset of neonatal sepsis due to group A streptococcus.
AB  - Neonatal infections by group A beta-hemolytic streptococcus are very rare in the
      antibiotic era. There are only a few cases in the first 72 hours after birth. The
      authors describe a case in which it was confirmed that the bacteria responsible,
      group A beta-hemolytic streptococcus, had grown in the newborn's blood and in the
      mother's lochia. The transmission mechanisms are also reviewed.

PMID- 11981532
TI  - [Diabetes and alternative medicine: diabetic patients experiences with Ayur-Ved,
      "clinical ecology" and "cellular nutrition" methods].
AB  - In the last two years we discovered that three of our patients with type 1
      diabetes mellitus (0.8%) suffered an unexpected worsening in their glycemic
      control due to a reduction of their insulin dosage in favour of some
      "alternative" diabetes treatments using herbs, vitamins, fantastic diets and
      trace elements prescribed by non-medical practitioners. The first patient, a 6.6
      year old boy, was admitted to hospital because of a severe ketoacidosis with
      first degree coma as a result of his parents having reduced his insulin dosage by
      77% and replacing the insulin with an ayurvedic herbal preparation (Bardana
      Actium Lapp). The second patient, a 10.4 year old boy, was admitted to hospital
      after his teachers noticed that he appeared tired, thinner and polyuric. During
      hospital admission for mild ketoacidosis the mother, reluctant at first, finally
      confessed that her son was under the care of a "clinical ecologist". Having
      identified several food allergies this "clinical ecologist" had placed the child
      on a spartan diet of bread, water and salt, and had reduced his insulin dosage by
      68%. The third patient, a 21 year old male, upon transfer to the Adult Diabetic
      Center, reported that he had been under the care of a pranotherapist for several
      years. The pranotherapist had prescribed a cellular nutrition preparation (called
      "Madonna drops"), a meditation program and also a 50% reduction in his insulin
      dosage. During this period his HbAlc values had increased from 6.4% to 12%.
      Current orthodox diabetes treatments are considered unsatisfactory by many people
      and it is thus not surprising that they search for "miracle" cures. It is
      important, however, that hospital staff do not ridicule the patients or their
      parents for trying these alternative therapies. Nevertheless, it would be useful
      for staff to discuss in advance these "therapies" with patients, highlighting
      their ineffectiveness and strongly discouraging cures that call for a reduction
      or elimination of the insulin treatment.

PMID- 11981533
TI  - Inflammatory bowel diseases in children.

PMID- 11981535
TI  - Turning back the clock.

PMID- 11981536
TI  - Investors remain wary after first quarter downturn.

PMID- 11981537
TI  - NIH outlines goals to counter bioterror.

PMID- 11981538
TI  - India approves GM cotton.

PMID- 11981539
TI  - Mexico to relax rDNA ban?

PMID- 11981540
TI  - Rice data release signals industry willingness to share data.

PMID- 11981541
TI  - Industry opposes genomic legislation.

PMID- 11981543
TI  - Rethinking somatic stem cell plasticity.

PMID- 11981544
TI  - A more astonishing hypothesis.

PMID- 11981545
TI  - Elan's attack of Enronitis.

PMID- 11981546
TI  - Protecting careers, not lives.

PMID- 11981547
TI  - Searching for alternatives.

PMID- 11981548
TI  - Cloning similarities.

PMID- 11981549
TI  - Biotechnology in the Medicon Valley.

PMID- 11981550
TI  - Finnish biotechnology--built on solid foundations.

PMID- 11981551
TI  - Time for consolidation in Germany.

PMID- 11981552
TI  - Nuclear reprogramming--alchemy or analysis?

PMID- 11981553
TI  - Expanding small RNA interference.

PMID- 11981554
TI  - Bringing picomolar protein detection into proximity.

PMID- 11981555
TI  - A new blueprint for plant pathogen resistance.

PMID- 11981557
TI  - Male and female mice derived from the same embryonic stem cell clone by
      tetraploid embryo complementation.
AB  - We have devised a general strategy for producing female mice from 39,X0 embryonic
      stem (ES) cells derived from male cell lines carrying a targeted mutation of
      interest. We show that the Y chromosome is lost in 2% of subclones from 40,XY ES
      cell lines, making the identification of targeted 39,X0 subclones a routine
      procedure. After gene targeting, male and female mice carrying the mutation can
      be generated by tetraploid embryo complementation from the 40,XY ES cell line and
      its 39,X0 derivatives. A single intercross then produces homozygous mutant
      offspring. Because this strategy avoids outcrossing and therefore segregation of
      mutant alleles introduced into the ES cells, the time and expense required for
      production of experimental mutant animals from a targeted ES cell clone are
      substantially reduced. Our data also indicate that ES cells have inherently
      unstable karyotypes, but this instability does not interfere with production of
      adult ES cell tetraploid mice.

PMID- 11981558
TI  - Reprogramming fibroblasts to express T-cell functions using cell extracts.
AB  - We demonstrate here the functional reprogramming of a somatic cell using a
      nuclear and cytoplasmic extract derived from another somatic cell type.
      Reprogramming of 293T fibroblasts in an extract from primary human T cells or
      from a transformed T-cell line is evidenced by nuclear uptake and assembly of
      transcription factors, induction of activity of a chromatin remodeling complex,
      histone acetylation, and activation of lymphoid cell specific genes. Reprogrammed
      cells express T cell specific receptors and assemble the interleukin-2 receptor
      in response to T cell receptor CD3 (TCR CD3) complex stimulation. Reprogrammed
      primary skin fibroblasts also express T cell specific antigens. After exposure to
      a neuronal precursor extract, 293T fibroblasts express a neurofilament protein
      and extend neurite-like outgrowths. In vitro reprogramming of differentiated
      somatic cells creates possibilities for producing isogenic replacement cells for
      therapeutic applications.

PMID- 11981559
TI  - Human erythroid cells produced ex vivo at large scale differentiate into red
      blood cells in vivo.
AB  - New sources of red blood cells (RBCs) would improve the transfusion capacity of
      blood centers. Our objective was to generate cells for transfusion by inducing a
      massive proliferation of hematopoietic stem and progenitor cells, followed by
      terminal erythroid differentiation. We describe here a procedure for amplifying
      hematopoietic stem cells (HSCs) from human cord blood (CB) by the sequential
      application of specific combinations of growth factors in a serum-free culture
      medium. The procedure allowed the ex vivo expansion of CD34+ progenitor and stem
      cells into a pure erythroid precursor population. When injected into nonobese
      diabetic, severe combined immunodeficient (NOD/SCID) mice, the erythroid cells
      were capable of proliferation and terminal differentiation into mature enucleated
      RBCs. The approach may eventually be useful in clinical transfusion applications.

PMID- 11981560
TI  - Protein detection using proximity-dependent DNA ligation assays.
AB  - The advent of in vitro DNA amplification has enabled rapid acquisition of genomic
      information. We present here an analogous technique for protein detection, in
      which the coordinated and proximal binding of a target protein by two DNA
      aptamers promotes ligation of oligonucleotides linked to each aptamer affinity
      probe. The ligation of two such proximity probes gives rise to an amplifiable DNA
      sequence that reflects the identity and amount of the target protein. This
      proximity ligation assay detects zeptomole (40 x 10(-21) mol) amounts of the
      cytokine platelet-derived growth factor (PDGF) without washes or separations, and
      the mechanism can be generalized to other forms of protein analysis.

PMID- 11981561
TI  - An array of target-specific screening strains for antibacterial discovery.
AB  - As the global threat of drug- and antibiotic-resistant bacteria continues to
      rise, new strategies are required to advance the drug discovery process. This
      work describes the construction of an array of Escherichia coli strains for use
      in whole-cell screens to identify new antimicrobial compounds. We used the
      recombination systems from bacteriophages lambda and P1 to engineer each strain
      in the array for low-level expression of a single, essential gene product, thus
      making each strain hypersusceptible to specific inhibitors of that gene target.
      Screening of nine strains from the array in parallel against a large chemical
      library permitted identification of new inhibitors of bacterial growth. As an
      example of the target specificity of the approach, compounds identified in the
      whole-cell screen for MurA inhibitors were also found to block the biochemical
      function of the target when tested in vitro.

PMID- 11981562
TI  - Large scale production of recombinant human lactoferrin in the milk of transgenic
      cows.
AB  - The limited capacity of current bioreactors has led the biopharmaceutical
      industry to investigate alternative protein expression systems. The milk of
      transgenic cattle may provide an attractive vehicle for large-scale production of
      biopharmaceuticals, but there have been no reports on the characteristics of such
      recombinant proteins. Here we describe the production of recombinant human
      lactoferrin (rhLF), an iron-binding glycoprotein involved in innate host defense,
      at gram per liter concentrations in bovine milk. Natural hLF from human milk and
      rhLF had identical iron-binding and -release properties. Although natural hLF and
      rhLF underwent differential N-linked glycosylation, they were equally effective
      in three different in vivo infection models employing immunocompetent and
      leukocytopenic mice, and showed similar localization at sites of infection. Taken
      together, the results illustrate the potential of transgenic cattle in the large
      scale production of biopharmaceuticals.

PMID- 11981563
TI  - An HGF-MSP chimera disassociates the trophic properties of scatter factors from
      their pro-invasive activity.
AB  - Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) have an
      intrinsic dual nature: they are trophic cytokines preventing apoptosis on one
      side and scatter factors promoting invasion on the other. For therapeutic use,
      their anti-apoptotic activity must be separated from their pro-invasive activity.
      To this end, we engineered chimeric factors containing selected functional
      domains of HGF and/or MSP in different combinations, and tested their biological
      activity. Here we present a chimeric cytokine derived from the alpha-chains of
      HGF and MSP, named Metron factor 1 for its ability to concomitantly activate the
      HGF receptor (Met) and the MSP receptor (Ron). We provide evidence that Metron
      factor 1 prevents apoptosis and stimulates cell proliferation at nanomolar
      concentrations, but is devoid of any pro-invasive activity. In an in vivo murine
      model of drug-induced nephrotoxicity, intravenous injection of recombinant Metron
      factor 1 prevented renal damage and preserved tubular integrity.

PMID- 11981564
TI  - U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress
      targeted gene expression in mammalian cells.
AB  - The first evidence for gene disruption by double-stranded RNA (dsRNA) came from
      careful analysis in Caenorhabditis elegans. This phenomenon, called RNA
      interference (RNAi), was observed subsequently in various organisms, including
      plants, nematodes, Drosophila, and protozoans. Very recently, it has been
      reported that in mammalian cells, 21- or 22-nucleotide (nt) RNAs with 2-nt 3'
      overhangs (small inhibitory RNAs, siRNAs) exhibit an RNAi effect. This is because
      siRNAs are not recognized by the well-characterized host defense system against
      viral infections, involving dsRNA-dependent inhibition of protein synthesis.
      However, the current method for introducing synthetic siRNA into cells by
      lipofection restricts the range of applications of RNAi as a result of the low
      transfection efficiencies in some cell types and/or short-term persistence of
      silencing effects. Here, we report a vector-based siRNA expression system that
      can induce RNAi in mammalian cells. This technical advance for silencing gene
      expression not only facilitates a wide range of functional analysis of mammalian
      genes but might also allow therapeutic applications by means of vector-mediated
      RNAi.

PMID- 11981565
TI  - Expression of small interfering RNAs targeted against HIV-1 rev transcripts in
      human cells.
AB  - RNA interference (RNAi) is the process of sequence-specific, posttranscriptional
      gene silencing in animals and plants initiated by double-stranded (ds) RNA that
      is homologous to the silenced gene. This technology has usually involved
      injection or transfection of dsRNA in model nonvertebrate organisms. The longer
      dsRNAs are processed into short (19 25 nucleotides) small interfering RNAs
      (siRNAs) by a ribonucleotide protein complex that includes an RNAse III related
      nuclease (Dicer), a helicase family member, and possibly a kinase and an RNA
      dependent RNA polymerase (RdRP). In mammalian cells it is known that dsRNA 30
      base pairs or longer can trigger interferon responses that are intrinsically
      sequence-nonspecific, thus limiting the application of RNAi as an experimental
      and therapeutic agent. Duplexes of 21-nucleotide siRNAs with short 3' overhangs,
      however, can mediate RNAi in a sequence-specific manner in cultured mammalian
      cells. One limitation in the use of siRNA as a therapeutic reagent in vertebrate
      cells is that short, highly defined RNAs need to be delivered to target cells--a
      feat thus far only accomplished by the use of synthetic, duplex RNAs delivered
      exogenously to cells. In this report, we describe a mammalian Pol III promoter
      system capable of expressing functional double-stranded siRNAs following
      transfection into human cells. In the case of the 293 cells cotransfected with
      the HIV-1 pNL4-3 proviral DNA and the siRNA-producing constructs, we were able to
      achieve up to 4 logs of inhibition of expression from the HIV-1 DNA.

PMID- 11981566
TI  - Effective expression of small interfering RNA in human cells.
AB  - In many eukaryotes, expression of nuclear-encoded mRNA can be strongly inhibited
      by the presence of a double-stranded RNA (dsRNA) corresponding to exon sequences
      in the mRNA (refs 1,2). The use of this "RNA interference" (RNAi) in mammalian
      studies had lagged well behind its utility in lower animals because uninterrupted
      RNA duplexes longer than 30 base pairs trigger generalized cellular responses
      through activation of dsRNA-dependent protein kinases. Recently it was
      demonstrated that RNAi can be made to work in cultured human cells by introducing
      shorter, synthetic duplex RNAs (approximately 20 base pairs) through liposome
      transfection. We have explored several strategies for expressing similar short
      interfering RNA (siRNA) duplexes within cells from recombinant DNA constructs,
      because this might allow long-term target-gene suppression in cells, and
      potentially in whole organisms. Effective suppression of target gene product
      levels is achieved by using a human U6 small nuclear RNA (snRNA) promoter to
      drive nuclear expression of a single RNA transcript. The siRNA-like parts of the
      transcript consists of a 19 base pair siRNA stem with the two strands joined by a
      tightly structured loop and a U1-4 3' overhang at the end of the antisense
      strand. The simplicity of the U6 expression cassette and its widespread
      transcription in human cell types suggest that this mode of siRNA delivery could
      be useful for suppressing expression of a wide range of genes.

PMID- 11981567
TI  - Using the transcriptome to annotate the genome.
AB  - A remaining challenge for the human genome project involves the identification
      and annotation of expressed genes. The public and private sequencing efforts have
      identified approximately 15,000 sequences that meet stringent criteria for genes,
      such as correspondence with known genes from humans or other species, and have
      made another approximately 10,000-20,000 gene predictions of lower confidence,
      supported by various types of in silico evidence, including homology studies,
      domain searches, and ab initio gene predictions. These computational methods have
      limitations, both because they are unable to identify a significant fraction of
      genes and exons and because they are unable to provide definitive evidence about
      whether a hypothetical gene is actually expressed. As the in silico approaches
      identified a smaller number of genes than anticipated, we wondered whether high
      throughput experimental analyses could be used to provide evidence for the
      expression of hypothetical genes and to reveal previously undiscovered genes. We
      describe here the development of such a method--called long serial analysis of
      gene expression (LongSAGE), an adaption of the original SAGE approach--that can
      be used to rapidly identify novel genes and exons.

PMID- 11981568
TI  - Quantitative proteome analysis by solid-phase isotope tagging and mass
      spectrometry.
AB  - The adaptation of sequences of chemical reactions to a solid-phase format has
      been essential to the automation, reproducibility, and efficiency of a number of
      biotechnological processes including peptide and oligonucleotide synthesis and
      sequencing. Here we describe a method for the site-specific, stable isotopic
      labeling of cysteinyl peptides in complex peptide mixtures through a solid-phase
      capture and release process, and the concomitant isolation of the labeled
      peptides. The recovered peptides were analyzed by microcapillary liquid
      chromatography and tandem mass spectrometry (microLC-MS/MS) to determine their
      sequences and relative quantities. The method was used to detect galactose
      induced changes in protein abundance in the yeast Saccharomyces cerevisiae. A
      side-by-side comparison with the isotope-coded affinity tag (ICAT) method
      demonstrated that the solid-phase method for stable isotope tagging of peptides
      is comparatively simpler, more efficient, and more sensitive.

PMID- 11981569
TI  - Patenting bioinformatic inventions: emerging trends in Europe.

PMID- 11981573
TI  - To recruit the best R&D professionals, understand what drives them.

PMID- 11981574
TI  - Diagnosis and treatment of urinary tract complications in Crohn's disease: an
      experience over 15 years.
AB  - BACKGROUND: Urinary tract complications in Crohn's disease are common but
      treatable, and often present diagnostic and therapeutic dilemmas. PURPOSE: To
      determine the incidence of urinary tract complications in patients with Crohn's
      disease in Israel and to report an experience over 15 years of patients with
      Crohn's disease, with the aim of illustrating the diverse patterns of
      presentation, and thereby broadening the approach to diagnosis and treatment.
      METHODOLOGY: Clinical and radiological findings of 312 patients with Crohn's
      disease were reviewed. RESULTS: Simple cystitis was the most common problem,
      occurring in 51 patients. The problem seldom required hospitalization and was
      instead managed in the ambulatory setting. A review revealed that 22 patients
      with urinary tract complications required hospitalization. Six patients had
      ileovesical fistulas. In one patient, the colon was also affected. In another
      patient, radiological and endoscopic studies failed to identify the fistula,
      which was confirmed during surgery. All six patients were treated surgically.
      Four patients had ureteral obstructions and hydronephrosis, three of whom
      responded well to conservative treatment. In one patient, the affected ileal
      segment was resected. Four patients suffered from retroperitoneal abscess
      accompanied by urinary symptoms. Twelve patients developed right kidney stones.
      All of the patients suffered from long-standing Crohn's disease with bowel
      resection. Surprisingly, most of the severe complications occurred in men,
      although 70% of the patients were women. CONCLUSIONS: Based on these findings,
      urological complications are not rare in patients with Crohn's disease, and
      necessitate a high degree of diligence and periodic urological evaluation.

PMID- 11981576
TI  - Recommendations for the appropriate use of anti-inflammatory drugs in the era of
      the coxibs: defining the role of gastroprotective agents.
AB  - Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional
      nonsteroidal anti-inflammatory drugs (NSAIDs) are compromised by a two- to
      fourfold increased risk of gastrointestinal complications. This increased risk
      has resulted in an increasing use of the new selective cyclooxygenase-2
      inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced
      gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs.
      However, the coxibs are not available to all patients who need them, and NSAIDs
      are still widely used. Moreover, treatment with a coxib cannot heal pre-existing
      gastrointestinal lesions, and cotherapy with an anti-secretory drug or mucosal
      protective agent may be required. This paper addresses the management of patients
      with risk factors for gastrointestinal complications who are taking NSAIDs and
      makes recommendations for the appropriate use of 'gastroprotective' agents (GPAs)
      in patients who need to take an NSAID or a coxib. When economically possible, a
      coxib alone is preferable to a conventional NSAID plus a GPA to minimize exposure
      to potential gastrointestinal damage and avoid unnecessary dual therapy. Patients
      at high risk require a GPA in addition to a coxib.

PMID- 11981577
TI  - Intestinal epithelial cells as a source of inflammatory cytokines and chemokines.
AB  - The intestinal epithelium has long been known to provide nonspecific defences
      such as mucus, lysozyme and transport of secretory immunoglobulin via the
      polyimmunoglobulin receptor. In the past decade, the realization emerged that
      enterocytes secrete molecules (cytokines) that regulate inflammation. As the
      focus tightened on this new role as sentinel, so has the interest in enterocyte
      production of cytokines with chemoattractant properties for leukocytes - the
      chemokines. Neutrophils are a prominent feature of the cellular infiltrate in
      various inflammatory diseases, and early reports indicated that epithelial cells
      secrete neutrophil chemoattractants. More recently, it has been shown that the
      cells also secrete chemokines for monocytes and lymphocytes. Some of these
      chemokines appear to be important in the uninflamed intestine but become
      increased during disease. While a great deal of knowledge has been gained
      regarding the circumstances leading to chemokine production by epithelial cells,
      the application of this understanding to the treatment of human intestinal
      diseases is lacking. Closing this gap is necessary to take advantage of emerging
      therapies aimed at blocking chemokine function.

PMID- 11981578
TI  - The physiology, pharmacology and therapeutic manipulation of the internal anal
      sphincter.
AB  - Recent research into the physiology and pharmacology of the internal anal
      sphincter has elucidated the importance of this structure in health and disease.
      Its pharmacological manipulation for therapeutic gain has focused mainly on
      agents to reduce internal anal sphincter tone, a 'chemical sphincterotomy' that
      might heal chronic anal fissure. However, drugs to increase sphincter tone, and
      augment intermittent and appropriate relaxation are also being evaluated. The
      initial results with this medical approach to anorectal disease have often been
      disappointing, failing to match the results achievable with surgery, and many of
      these drugs have a high rate of side effects in the short term. However, clinical
      trials have yet to establish the optimum doses, dose intervals and routes of
      administration for many of these therapies. Furthermore, it is uncertain whether
      this medical approach should be applied to all patients or just to an as yet
      undefined subgroup. Certainly, even in the current environment of uncertainty,
      there is little reason not to try medical manipulation of the internal sphincter
      as first-line treatment. Surgery remains an option for treatment failures;
      patients responding to pharmacological manipulation of the internal anal
      sphincter are spared the long term risks of continence that are inherent in many
      surgical procedures on the anorectum.

PMID- 11981580
TI  - Perspectives on hyperhomocysteinaemia and arterial atherosclerosis.

PMID- 11981581
TI  - Dangerous and life-threatening drugs - practical lessons from the long QT
      syndrome.
AB  - The long QT syndrome (LQTS) is caused by delayed cardiac repolarisation and may
      be associated with ventricular arrhythmias (torsades de pointes) and sudden
      death. The congenital LQTS is caused by mutations in any one of many genes coding
      for ion channels responsible for cardiac repolarisation. The acquired LQTS is
      much more common and may be associated with various metabolic conditions,
      acquired heart disease or drugs. The apparent idiosyncratic development of QT
      prolongation under these circumstances may well expose a much larger population
      with silent genetic mutations. Attention has focused on the growing list of drugs
      implicated in the causation of the syndrome and this has led to the withdrawal of
      some drugs and new guidelines for the pre-clinical and clinical testing of new
      drugs. Clinicians should be aware of the drugs that may cause this syndrome and
      its potentially fatal arrhythmias, as well as the conditions that make patients
      more vulnerable. Patients should be made aware of the risk of drug interactions
      and precautions when prescribed these drugs. Adverse drug effects suggestive of
      cardiac arrhythmias should be reported to drug regulatory authorities. The LQTS
      has vastly expanded our knowledge of the molecular and genetic basis of cardiac
      repolarisation and arrhythmogenesis and its clinical significance is increasing.

PMID- 11981582
TI  - The detection of myocardial viability and its clinical implications.
AB  - The mortality, morbidity and economic burden imposed by congestive heart failure
      are considerable. Despite a prevalence and prognosis comparable to the more
      commonly encountered cancers like breast and lung cancer, there has been
      relatively less emphasis in the western world on the screening, diagnosis and
      treatment of heart failure, at least until recently. This may be partly
      attributed to the fact that the complex pathophysiology of heart failure was ill
      understood and the heterogeneity of the syndrome not recognised, so that even
      among specialist cardiologists it was considered pretty much an irreversible
      condition amenable only to palliative therapy. However, our understanding of
      heart failure has grown significantly in the past decade. From the early days
      when all dysfunctional myocardium was considered necrosed, and revascularisation
      often dismissed on this basis, we have now progressed to the understanding that
      dysfunctional myocardium is a heterogeneous entity comprising necrotic, stunned,
      hibernating and myopathic myocardium, and that the therapeutic objectives in each
      of these categories is specific and should be addressed individually. In this
      article we briefly review the pathophysiology, and diagnostic and therapeutic
      implications of reversible ischaemic left ventricular dysfunction.

PMID- 11981583
TI  - Echocardiographic features of extreme mitral valve prolapse vs mitral valve
      aneurysm.
AB  - This report presents clinical observations and brings up for discussion the
      differential diagnosis of echocardiographic features of extreme mitral valve
      prolapse and inflammatory and non-inflammatory mitral valve aneurysms.

PMID- 11981584
TI  - Premature thelarche: identification of clinical and laboratory data for the
      diagnosis of precocious puberty.
AB  - PURPOSE: Two groups of girls with premature breast development were studied
      retrospectively. We tried to identify clinical, radiological, and hormonal
      parameters that could distinguish between a benign, nonprogressive premature
      thelarche and a true precocious puberty. METHODS: The clinical outcome of 88
      girls with breast enlargement before 6.1 years of age was analyzed. Taking into
      account the progression of their sexual maturation, we allocated the children
      into 2 groups: "Isolated Premature Thelarche" (n = 63) and "Precocious Puberty"
      (n = 25) groups. Chronological and bone ages, height and growth velocity
      centiles, computerized tomography of hypothalamus-pituitary area, pelvic
      ultrasonography, gonadotropin response to luteinizing hormone-releasing hormone
      stimulation as well as basal levels of luteinizing hormone, follicle-stimulating
      hormone, estradiol, and prolactin were studied in both groups. Statistical
      analysis were performed using the Student t test to compare the sample means.
      Fisher's exact test and chi2 test were used to analyze the nonparametric
      variables. RESULTS: Isolated premature thelarche most frequently affected girls
      younger than 2 years who presented exaggerated follicle-stimulating hormone
      response to luteinizing hormone-releasing hormone stimulation test. The
      precocious puberty group had higher initial stature, accelerated growth rate and
      bone age, increased uterine and ovarian volumes, high spontaneous luteinizing
      hormone levels by immunofluorimetric assay, as well as a high luteinizing hormone
      response and peak luteinizing hormone/follicle-stimulating hormone ratio after
      luteinizing hormone-releasing hormone stimulation. CONCLUSION: At initial
      presentation, girls who undergo true precocious puberty present advanced bone
      age, increased uterine and ovarian volumes in addition to breast enlargement, as
      well as an luteinizing hormone-predominant response after a luteinizing hormone
      releasing hormone stimulation test.

PMID- 11981585
TI  - Pelvic lymphoscintigraphy: contribution to the preoperative staging of rectal
      cancer.
AB  - PURPOSE: Preservation of the anal sphincter in surgery for cancer of the distal
      rectum in an attempt to avoid colostomy has been a main concern of colorectal
      surgeons. Various proposed procedures contradict oncological principles,
      especially with respect to pelvic lymphadenectomy. Therefore, prior knowledge of
      pelvic lymph node involvement is an important factor in choosing the operative
      technique, i.e., radical or conservative resection. Introduction of ultrasound,
      computerized tomography, and magnetic resonance have made preoperative study of
      the area possible. Nevertheless, these resources offer information of an
      anatomical nature only. Lymphoscintigraphy enables the morphological and
      functional evaluation of the pelvic area and contributes toward complementing the
      data obtained with the other imaging techniques. The objective of this
      prospective study is twofold: to standardize the lymphoscintigraphy technique and
      to use it to differentiate patients with rectal cancer from those with other
      coloproctologic diseases. CASUISTIC AND METHODS: Sixty patients with various
      coloproctologic diseases were studied prospectively. Ages ranged from 21 to 96
      years (average, 51 and median, 55 years). Twenty-six patients were male and 34
      were female. Thirty patients had carcinoma of the distal rectum as diagnosed by
      proctologic and anatomic-pathologic examinations, 20 patients had hemorrhoids, 5
      had chagasic megacolon, 2 had diverticular disease, 2 had neoplasm of the right
      colon, and 1 had ulcerative colitis as diagnosed by proctologic exam and/or
      enema. The lymphoscintigraphy method consisted of injecting 0.25 mL of a dextran
      solution marked with radioactive technetium-99m into the right and left sides of
      the perianal region and obtaining images with a gamma camera. The results were
      analyzed statistically with a confidence level of 95% (P <.05) using the
      following statistical techniques: arithmetic and medium average, Fisher exact
      test, chi-square test corrected for continuity according to Yates, and
      distribution tables for the number of patients. RESULTS: In rectal cancer, the
      tracer progresses unilaterally or is absent; in other patients, the progress of
      the tracer is bilateral and symmetrical, although its progress may be slow.
      Statistical tests showed with high significance that the agreement index between
      the clinical diagnosis and the result of the lymphoscintigraphic exam was 93%.
      CONCLUSIONS: Lymphoscintigraphy is a standardized, painless, and harmless test
      that can be performed in all cases; it differentiates patients with rectal cancer
      from those with other coloproctological diseases.

PMID- 11981586
TI  - Pancreatic lesions in acute experimental Chagas' disease.
AB  - BACKGROUND: Chagas' disease is an endemic tropical affliction found from southern
      United States to Argentina. The acute phase of this disease is difficult to study
      in man because the symptoms are non-specific and most cases require no medical
      assistance. Experimental models have been developed for sequential studies, and
      intense parasitism in all organs and tissues, including the pancreas, have been
      detected in the acute phase. PURPOSE: To evaluate the involvement of the pancreas
      in acute experimental Chagas' disease in a mouse model by histopathological
      characterization. CASUISTIC AND METHODS: Ten BALBc mice, about 20 g, injected
      i.p. with 100 000 forms of the Y strain of Trypanosoma cruzi were used. The
      animals were sacrificed after 14 days of infection. Fragments of pancreas were
      processed by conventional paraffin embedding and hematoxylin-eosin staining.
      RESULTS: Ruptured pseudocysts and release of parasites to the extracellular
      medium caused by necrosis of acinar and duct cells and foci of fat were the most
      striking histopathological features of acute Chagasic pancreatitis. CONCLUSION:
      Parasitism is the main cause of acute pancreatitis in Chagas' disease.

PMID- 11981587
TI  - Primary rhabdomyosarcoma of the diaphragm: case report and literature review.
AB  - The authors report a case of primary rhabdomyosarcoma of the diaphragm, an
      extremely rare presentation with only 14 cases reported in the literature. An 18
      year-old male presented 2 spontaneous occurrences of pneumothorax. Computed
      tomography and magnetic resonance showed a tumoral mass on the right
      diaphragmatic surface, and after biopsy, the diagnosis was compatible with
      spindle cell rhabdomyosarcoma. Because the visceral pleura was invaded by the
      tumoral mass, a right pleuropneumonectomy was performed. The patient received
      adjuvant chemotherapy, and there was no evidence of disease 15 months after the
      operation. Based on the Intergroup Rhabdomyosarcoma Study Group (IRSG) criteria,
      which consider the extent of the disease and its surgical resectability,
      rhabdomyosarcomas can be classified into 4 groups. In clinical group I, which was
      the classification of our patient, the tumor is localized and completely
      resectable, which implies a good prognosis. Rhabdomyosarcoma is a rare tumor, and
      a good outcome may result if it is completely resected.

PMID- 11981588
TI  - Agenesis of the posterior arch of the atlas.
AB  - PURPOSE: To illustrate the radiological findings and review the current
      literature concerning a rare congenital abnormality of the posterior arch of the
      atlas. CASE REPORT: An adult female without neurological symptoms presented with
      an absent posterior arch of the atlas, examined with plain films and helical
      computerized tomography. Complete agenesis of the posterior arch of the atlas is
      a rare entity that can be easily identified by means of plain films. Although it
      is generally asymptomatic, atlantoaxial instability and neurological deficits may
      occur because of structural instability. Computerized tomography provides a means
      of assessing the extent of this abnormality and can help evaluate the integrity
      of neural structures. Although considered to be rare entities, defects of the
      posterior arch of the atlas may be discovered as incidental asymptomatic findings
      in routine cervical radiographs. Familiarity with this abnormality may aid
      medical professionals in the correct management of these cases.

PMID- 11981589
TI  - Familial hyperamylasemia.
AB  - A 7-year-old white boy was referred to us with a history of 3 attacks of
      hypogastric pain over the previous 2 years and persistently elevated serum
      amylase concentrations. At physical examination, he was well with no evidence of
      clinical abnormalities. His weight and height were normal. Laboratory diagnostic
      investigations were all normal except for the presence of Ascaris lumbricoides in
      the feces and persistently elevated serum amylase levels. Serum amylase
      determinations in the family members were normal in his father and maternal
      grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of
      whom asymptomatic. Macroamylasemia was excluded in the child and in the mother.
      The finding of persistently elevated amylasemia in the child and in the other
      family members spanning 3 generations, and the exclusion of diseases that lead to
      hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia.
      Until now, only 1 similar case has been reported. Familial hyperamylasemia must
      be considered in the differential diagnosis of hyperamylasemias in childhood.

PMID- 11981590
TI  - Reversal of stress- and CRF-induced anorexia in rats by the synthetic
      nociceptin/orphanin FQ receptor agonist, Ro 64-6198.
AB  - RATIONALE: (1S,3aS)-8-(2,3,3,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8
      triazaspiro[4.5]decan-4-one (Ro 64-6198), a non-peptidic agonist for the opioid
      receptor-like1 (ORL1) receptor, exhibits anxiolytic properties in stressful
      conditions. OBJECTIVE: The present study was aimed at evaluating whether
      activation of ORL1 receptors by Ro 64-6198 may reverse the anorectic effect of
      restraint stress or intracerebroventricular (ICV) CRF injection. METHODS: In body
      restraint experiments, 20-h food deprived rats were treated with intraperitoneal
      (IP) injection of Ro 64-6198 or vehicle. Ten minutes later, they were confined in
      cylindrical Plexiglas tubes for 60 min and then returned to their cage with food.
      In CRF experiments, 20-h food deprived rats were IP injected with Ro 64-6198 or
      vehicle. Ten minutes later, they received ICV CRF, 200 ng/rat or vehicle; food
      was offered after 20 min. RESULTS: Intraperitoneal (IP) pretreatment with Ro 64
      6198 reversed the hypophagic effect induced by both restraint or CRF; the effect
      was statistically significant at the three doses tested (0.3, 1.0 or 2.5 mg/kg).
      ICV administration of the selective ORL1 receptor antagonist [Nphe(1)]NC(1
      13)NH(2)(two injections of 33 or 66 microg/rat) abolished the effect of Ro 64
      6198 on CRF-induced anorexia. In freely feeding rats, Ro 64-6198 significantly
      increased feeding at 2.5, but not at 0.3 or 1.0 mg/kg; in food deprived rats, Ro
      64-6198 (0.3 or 1.0 mg/kg) did not modify food intake. Thus, reversal of stress-
      and CRF-induced anorexia by Ro 64-6198 can be evoked at doses lower than those
      that are hyperphagic. Ro 64-6198 (1 or 2.5 mg/kg) did not modify the anorectic
      effect of E. coli lipopolysaccharide, suggesting that its effect is selective for
      stress- or CRF-induced anorexia. Lastly, the benzodiazepine diazepam was unable
      to reduce the anorectic effect of CRF at the anxiolytic dose of 0.3 mg/kg, and
      partially reduced it at the hyperphagic dose of 1 mg/kg. CONCLUSIONS: The results
      of this study show that the non-peptidic ORL1 receptor agonist Ro 64-6198
      markedly and selectively inhibits the anorectic effect of stress and CRF, and
      provide evidence that this effect is mediated by ORL1 receptors. Thus, Ro 64-6198
      may represent an interesting tool for treatment of stress-induced anorexia.

PMID- 11981591
TI  - The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated
      behavior in rodents.
AB  - RATIONALE: The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha
      THP) has been previously shown to induce catalepsy in mice that is modified by
      GABAergic, dopaminergic, adenosinergic and serotonergic agents. In light of the
      interaction of this endogenous neurosteroid with GABAergic and dopaminergic
      transmission, there is potential interest in the possible role of 3alpha,5alpha
      THP in psychotic disorders. OBJECTIVE: This study assessed the effect of
      3alpha,5alpha-THP in certain dopamine-mediated behavioral paradigms that are
      widely used to predict antipsychotic-like activity. METHODS: 3alpha,5alpha-THP (1
      8 microg per animal, i.c.v.), the classic neuroleptic (dopamine receptor
      antagonist) haloperidol (0.25 mg/kg, i.p.), and the benzodiazepine diazepam (7
      mg/kg, i.p.) were injected into different groups of animals, and their behavior
      was screened using the following animal tests: conditioned avoidance response,
      apomorphine-induced climbing, and amphetamine-induced motor hyperactivity.
      Separate groups of mice that received 3alpha,5alpha-THP (1-8 microg per animal,
      i.c.v.) were screened for catalepsy. Furthermore, the effect of a sub-cataleptic
      dose (0.1 microg per mouse, i.c.v.) of 3alpha,5alpha-THP, either alone or in
      combination with the GABA(A) receptor antagonist picrotoxin (0.8 mg/kg, i.p.) was
      measured on haloperidol-induced catalepsy. RESULTS: 3alpha,5alpha-THP like
      haloperidol reduced conditioned avoidance, apomorphine-induced cage climbing and
      amphetamine-induced motor hyperactivity. Diazepam only affected conditioned
      avoidance. 3alpha,5alpha-THP also induced dose-dependent catalepsy. Furthermore,
      sub-cataleptic doses of 3alpha,5alpha-THP potentiated haloperidol-induced
      catalepsy. This potentiation was blocked by prior treatment with the GABA(A)
      receptor antagonist picrotoxin. CONCLUSION: These findings suggest that
      3alpha,5alpha-THP, by its action at the GABA(A) receptors, increases GABAergic
      tone leading to a behavioral profile similar to that of dopamine receptor
      antagonists.

PMID- 11981592
TI  - Metabolic mapping of the time-dependent effects of delta 9-tetrahydrocannabinol
      administration in the rat.
AB  - RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) has a long duration of action.
      Studies have shown that effects on some behavioral endpoints can persist for as
      long as 24 h after exposure, but the neural substrates underlying these long
      lasting effects have not yet been determined. OBJECTIVES: The purpose of the
      present study was to identify the neuroanatomical substrates associated with the
      temporal course of the effects of the acute administration of moderate to high
      doses of THC using the quantitative autoradiographic 2-[(14)C]deoxyglucose (2DG)
      method. METHODS: Male Sprague-Dawley rats ( n=4-5 per group) were administered
      THC (0.0, 2.5 or 10 mg/kg, intraperitoneally), and the 2DG procedure was
      initiated 15 min, 6 h, or 24 h after treatment. To establish the behavioral
      profile of THC administration, locomotor activity and core body temperature were
      measured at corresponding time points. RESULTS: The administration of THC
      produced widespread dose-dependent reductions in rates of cerebral metabolism
      when the 2DG method was applied 15 min after treatment. A more limited set of
      structures was affected when the 2DG method was applied 6 h after THC
      administration, closely paralleling the effects of THC on locomotor activity and
      core body temperature. However, 24 h after administration, glucose utilization
      remained depressed within mesolimbic and amygdalar regions. CONCLUSIONS: These
      data demonstrate that the functional consequences of acute administration of THC
      follow a distinct temporal course that is regionally specific. That functional
      activity remains depressed in areas involved in the processing of motivational
      and emotional information suggests that behaviors subserved by these structures
      (e.g. anxiety, stress, and reward) may remain altered for as long as 24 h after a
      single exposure to THC.

PMID- 11981593
TI  - Nighttime versus daytime hypnotic self-administration.
AB  - RATIONALE AND OBJECTIVES: Previous studies have shown that insomniacs self
      administer hypnotics at high nightly rates. This study assessed whether
      insomniacs' self-administration of hypnotics extended to the daytime. METHODS:
      Forty-four healthy men and women, 21-55 years old, with ( n=22) and without (
      n=22) insomnia volunteered. They were randomized to one of two triazolam dose
      groups (0.125 or 0.25 mg) and their preference for placebo versus triazolam was
      assessed at night (2300 hours) and day (0900 hours) over 7 consecutive days in
      each phase. In both night and day phases of the study, subjects received
      triazolam or placebo in color-coded capsules on two sampling days or nights and
      then were forced to choose their preferred capsule on 5 subsequent days or
      nights. The order of day and night study phases and the placebo and triazolam
      sampling days was counterbalanced. In the night phase subjects went to bed from
      2330 to 0730 hours and in the day phase they were tested for level of sleepiness
      alertness at 1000, 1200, 1400, and 1600 hours by the multiple sleep latency test
      (MSLT) and mood and performance at 1100 and 1500 hours. RESULTS: More triazolam
      was chosen at night than during the day. No dose differences in preferences at
      night versus day or between insomniacs and normals were found. Insomniacs did not
      differ in their triazolam preferences between night and day, while the normals
      chose triazolam less frequently during the day. Among insomniacs, 40% chose
      triazolam on >3 of the 5 days. On both screening and placebo sampling days, those
      with a high (>60%) daytime triazolam preference had greater average daily sleep
      latencies on the MSLT than those with a low (<50%) daytime triazolam preference
      (i.e. with a placebo preference). In the triazolam preference group, triazolam
      reduced daily MSLT latencies to the level of the placebo preference group.
      CONCLUSIONS: This study shows that the minority of insomniacs who self-administer
      hypnotics during the day are physiologically aroused and the drug reduces their
      arousal suggesting that their daytime self-administration, like their night-time
      self-administration, is more consistent with therapy-seeking than drug-seeking
      behavior, at least for the short-term.

PMID- 11981594
TI  - Treatment strategies in patients with major depression not responding to first
      line sertraline treatment. A randomised study of extended duration of treatment,
      dose increase or mianserin augmentation.
AB  - RATIONALE: A large proportion of patients with major depression do not respond
      sufficiently to any first-line treatment. OBJECTIVES: The aim of this study was
      to compare a strategy of sertraline dose increase with a strategy of adding
      mianserin in patients with major depression insufficiently responding to 6 weeks
      of open treatment with sertraline, controlling for the effect of an extended
      duration of treatment. METHODS: One thousand six hundred and twenty-nine
      patients, 18-65 years of age, with major depression scoring at least 18 on the 17
      item Hamilton depression scale (HDS) were treated openly with 50 mg/day
      sertraline, and patients who after 4 weeks had not responded (achieving at least
      a 50% reduction in score on the HDS) were treated with 100 mg/day sertraline for
      an additional 2-week period. The patients who had still not responded were then
      randomised to double-blind treatment for an additional 5 weeks with either 100
      mg/day sertraline plus placebo, 200 mg/day sertraline plus placebo or 100 mg/day
      sertraline plus 30 mg/day mianserin. RESULTS: After 6 weeks of open treatment,
      60% had responded and 22% had dropped out, leaving 295 non-responding patients
      (18%) for randomisation. In the intention-to-treat-analysis, continuing the
      treatment with 100 mg/day sertraline resulted in response in 70% of the non
      responders, similar to the response rate (67%) obtained in the patients who had
      mianserin added. However, increasing the sertraline dose to 200 mg/day resulted
      in a lower response rate at 56% ( P<0.05). Similar results were seen in the
      completers. A substantial increase in the accumulated response rate from week 6
      to week 8 was seen. There was no influence of baseline variables, including the
      presence of melancholic features on the overall post-randomisation response rate.
      CONCLUSION: After 6 weeks of insufficient antidepressant treatment with 50-100
      mg/day sertraline, a continued treatment with 100 mg/day sertraline can be
      considered until at least week 8 before considering changing strategy, unless the
      condition deteriorates.

PMID- 11981595
TI  - Differential involvement of mu-opioid receptors in the rostral versus caudal
      nucleus accumbens in the reinforcing effects of heroin in rats: evidence from
      focal injections of beta-funaltrexamine.
AB  - RATIONALE: The nucleus accumbens is a diverse and heterogeneous structure along
      its rostrocaudal axis. The influence of specific subpopulations of mu-opioid
      receptors within the NAcc in heroin self-administration has not been documented.
      OBJECTIVES: This study was undertaken to investigate the involvement of
      subregions of the NAcc in heroin self-administration in rats. METHODS: Male rats
      were trained to self-administer heroin and then given beta-FNA, an irreversible
      mu-opioid receptor antagonist, into either the rostral or caudal portion of the
      NAcc. RESULTS: beta-FNA (0.25-2.5 nmol) attenuated heroin self-administration in
      a dose-responsive manner when given into the caudal but not rostral NAcc. The
      number of infusions of 18 microg of heroin self-administered was increased by 50
      100%. This effect persisted for up to 17 days following administration of the
      highest dose. These doses of beta-FNA were found to decrease [(3)H]DAMGO binding
      in a dose-responsive manner and the effect was confined to the NAcc, as nearby
      structures such as the caudate putamen and olfactory tubercles were unaffected.
      The effect of beta-FNA (2.5 nmol) administration into the caudal NAcc was also
      assessed on the dose-effect curve for heroin. This dose apparently shifted the
      dose-effect curve to the right initially, followed by an apparent upward shift
      for up to 17 days after beta-FNA administration. CONCLUSIONS: The caudal portion
      of the NAcc and its output sites merit further investigation regarding the
      reinforcing effects of heroin.

PMID- 11981596
TI  - Reduced aggression in mice lacking the serotonin transporter.
AB  - RATIONALE: Dysregulation of the brain serotonergic system has been implicated in
      the pathophysiology of violence and aggression. As a key regulator of central
      serotonergic activity, dysfunction of the serotonin transporter (5-HTT)
      represents a potential mechanism mediating pathological aggression. OBJECTIVES:
      To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage
      activity and 5-HT(1A/1B) receptor function in 5-HTT KO mice as factors
      contributing to an aggressive phenotype. METHODS: Isolated male 5-HTT KO mice
      were compared to +/+ control mice using the resident-intruder test for aggression
      over two encounters. Locomotor activity was measured in the home cage over a 24-h
      period. 5-HT(1A/1B) receptor function was assessed via the pharmacological
      effects of the 5-HT(1A/1B) receptor agonist, RU24969, on locomotion. RESULTS: 5
      HTT -/- mice were slower to attack the intruder and attacked with less frequency
      than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice
      were as quick to attack, but made fewer overall attacks, as compared to +/+
      controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/-
      and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian
      pattern of home cage activity, but less activity overall, as compared to 5-HTT +/
      and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and
      +/+, but not 5-HTT -/- mice. CONCLUSIONS: Deletion of the 5-HTT gene produces a
      reduction in aggressive behavior and home cage activity. Desensitization of 5
      HT(1A/1B) receptor function may contribute to reduced aggression in 5-HTT KO
      mice.

PMID- 11981597
TI  - Effects of acute and repeated systemic administration of ketamine on prefrontal
      acetylcholine release and sustained attention performance in rats.
AB  - RATIONALE: The effects of non-competitive N-methyl- D-aspartate (NMDA) receptor
      antagonists model aspects of schizophrenic symptomatology. Because effects on
      both cortical cholinergic transmission and attentional processes have been
      hypothesized to represent components of the properties of psychotogenic drugs,
      the present study investigated the effects of ketamine on the activity of
      cortical cholinergic inputs and attentional performance. OBJECTIVE: To determine
      the effects of acute and repeated ketamine administration on cortical
      acetylcholine release and performance of rats in an operant task designed to
      assess sustained attention performance. METHODS: Experiment 1 assessed the
      effects of ketamine (2.0-20.0 mg/kg, i.p.) on medial prefrontal acetylcholine
      release using in vivo microdialysis. In experiment 2, animals were pretreated
      with 2.0 mg/kg or 25.0 mg/kg ketamine for 7 days. Cortical acetylcholine release
      was assessed in these rats following the subsequent administration of a
      'challenge' dose of 2.0 mg/kg on days 1, 8, and 15 following completion of the
      pretreatment regimen. Experiment 3 assessed the effects of acute ketamine
      administration (2.0, 4.0, and 8.0 mg/kg, i.p.) on sustained attention
      performance. In experiment 4, animals trained in the sustained attention task
      were pretreated with 25.0 mg/kg ketamine or vehicle for 7 days. In these animals,
      the performance effects of 2.0 mg/kg ketamine administered 1, 8, or 15 days after
      completion of the pretreatment regimen were assessed. RESULTS: The acute
      administration of ketamine dose dependently increased cortical acetylcholine
      release by up to 250% above baseline and for over 40 min following the highest
      dose of ketamine. Pretreatment with 2.0 mg or 25.0 mg/kg did not robustly alter
      the effects of subsequent ketamine administration on cortical acetylcholine
      release. In animals performing the sustained attention task, administration of
      the highest dose of ketamine resulted in high levels of errors of omission, while
      the administration of the two smaller doses did not affect performance.
      Pretreatment with 25.0 mg/kg disrupted the attentional performance during the
      pretreatment period, but it did not affect the baseline performance thereafter.
      Furthermore, ketamine pretreatment did not systematically alter the performance
      effects of subsequent ketamine administration. CONCLUSIONS: The robust
      stimulation of cortical acetylcholine release represents a potent component of
      the pharmacological effects of ketamine. The effects of acute ketamine on
      attentional performance were limited to high rates of omissions. Repeated
      ketamine administration 'sensitized' neither cortical acetylcholine release nor
      attentional performance. These effects of repeated ketamine differ substantially
      from those of another major psychotogenic drug, amphetamine, and thus support the
      view that ketamine and amphetamine model fundamentally different aspects of
      schizophrenia.

PMID- 11981598
TI  - Role of GABAA/benzodiazepine receptors containing alpha 1 and alpha 5 subunits in
      the discriminative stimulus effects of triazolam in squirrel monkeys.
AB  - RATIONALE: Conventional benzodiazepines (BZs), clinically used for treatment of
      anxiety and insomnia, bind to GABA(A) receptors containing alpha(1), alpha(2),
      alpha(3), or alpha(5) subunits. The role of these different GABA(A) receptor
      subtypes in mediating the subjective effects of BZs remains largely unknown.
      OBJECTIVE: The purpose of the present study was to evaluate the role of GABA(A)
      receptors containing the alpha(1) or alpha(5) subunits in the discriminative
      stimulus (DS) effects of the conventional BZ agonist triazolam. METHODS: Squirrel
      monkeys were trained to discriminate triazolam (0.03 mg/kg, i.v.) from vehicle
      under a fixed-ratio 10 schedule of food reinforcement. RESULTS: The
      GABA(A)/alpha(1)-preferring agonists zolpidem and zaleplon engendered responses
      predominantly on the triazolam lever (73-80% drug-lever responding), and the
      GABA(A)/alpha(1) partial agonist CL 218,872 engendered an average maximum of less
      than 50% triazolam-lever responding. The GABA(A)/alpha(1)-preferring antagonists
      beta-carboline-3-carboxylate-t-butyl ester (betaCCT) and 3-(propyloxy)-beta
      carboline (3-PBC) blocked the DS effects of triazolam and zolpidem in a
      surmountable manner. Schild analyses for betaCCT and 3-PBC in combination with
      triazolam and zolpidem suggest that the interactions between these compounds were
      competitive in nature and mediated by a common population of receptors,
      presumably GABA(A)/alpha(1) receptors. In contrast, the GABA(A)/alpha(5)
      preferring agonist QH-ii-66 did not engender triazolam-lever responding
      regardless of dose and did not alter the DS effects of triazolam when
      administered in combination. CONCLUSIONS: The results are consistent with
      GABA(A)/alpha(1) receptor involvement in mediating the DS effects of triazolam.
      In contrast, binding to GABA(A)/alpha(5) receptors may not play a critical role
      in mediating triazolam's DS effects.

PMID- 11981599
TI  - Dopamine agonist effects on startle and sensorimotor gating in normal male
      subjects: time course studies.
AB  - RATIONALE: Prepulse inhibition (PPI) of startle is a measure of sensorimotor
      gating that is deficient in schizophrenia and in rodents treated with dopamine
      (DA) agonists. Reduced PPI is reported in normal humans treated with direct or
      indirect DA agonists. To facilitate future studies, we assessed the time course
      of DA agonist effects on PPI in humans, for both direct (bromocriptine: 1.25, 2.5
      mg; pergolide: 0.025, 0.1 mg) and indirect DA agonists (amphetamine: 20 mg;
      amantadine: 200 mg) ( n=6-10/dose). METHODS: Baseline (no drug) levels of
      acoustic and tactile startle, as well as uni- and cross-modal PPI, were assessed
      in 63 normal adult males. Seven to ten days later, subjects were tested in five
      sessions over 3.5 h after ingestion of placebo or active drug in a double-blind
      design. RESULTS: Expected drug effects were observed in both autonomic (for
      example, increased heart rate and blood pressure with amphetamine), somatic (for
      example, "queasiness" with direct DA agonists), and psychological measures (for
      example, "happiness", less "drowsiness" with amphetamine). Drugs increased
      (bromocriptine) or decreased (amantadine) startle magnitude, and caused either no
      change or modest, time-dependent effects on PPI. Amantadine increased PPI over
      the test session, a pattern not observed with other DA agonists or placebo. No
      consistent effects on PPI were observed with either bromocriptine, pergolide, or
      amphetamine. Drug effects on startle did not consistently correlate with self
      assessment measures. CONCLUSIONS: Despite evidence of "bioactivity", under the
      specific experimental conditions of this study, neither direct nor indirect DA
      agonists had robust effects on startle or PPI. In some cases (for example,
      amantadine), a time course was identified that will facilitate future studies of
      DA agonist effects on PPI in humans.

PMID- 11981600
TI  - High-dose methadone produces superior opioid blockade and comparable withdrawal
      suppression to lower doses in opioid-dependent humans.
AB  - RATIONALE: The efficacy of methadone for treating heroin dependence derives, in
      part, from suppression of opiate withdrawal and attenuation of the effects of
      heroin. OBJECTIVES: The purpose of this double-blind, within-subject, inpatient
      study was to determine whether larger doses of methadone, which are more
      effective in the treatment of opioid dependence, produce greater or longer
      lasting blockade of the effects of heroin in addition to adequate withdrawal
      suppression. METHODS: Participants were maintained on 30, 60, and 120 mg
      methadone (ascending order) for approximately 3 weeks at each dose. During each
      maintenance period, heroin challenges were administered at 4, 28, and 52 h after
      the last methadone dose. Opioid agonist effects and opioid withdrawal symptoms
      were assessed prior to heroin challenge. Challenge sessions consisted of three
      doses of heroin (0, 10, and 20 mg/70 kg; ascending order) 45 min apart. RESULTS:
      All three methadone maintenance doses produced similar agonist effects.
      Participants tested 4 h after receiving 120 mg methadone showed complete
      suppression of withdrawal symptoms and full attenuation of the effects of heroin.
      Thirty and 60 mg methadone suppressed withdrawal for up to 52 h, but failed to
      block completely the effects of heroin. The effects of heroin increased slightly
      at longer post-methadone intervals. CONCLUSIONS: Heroin use may persist during
      methadone treatment because low to moderate doses of methadone suppress
      withdrawal, but fail to eliminate the effects of heroin. These results provide a
      mechanism for the clinical observation that higher methadone doses are more
      effective at reducing heroin use.

PMID- 11981601
TI  - The middle glenohumeral ligament: normal anatomy, variants and pathology.
AB  - The middle glenohumeral ligament frequently presents variations of the normal
      anatomy and it is often injured in patients suffering trauma to the glenohumeral
      joint. The purpose of this pictorial assay is to illustrate the normal anatomy,
      biomechanics, normal variants and pathology of the middle glenohumeral ligament,
      as shown on MRI and MR arthrography of the shoulder.

PMID- 11981602
TI  - MR detection of iliac bone marrow involvement by malignant lymphoma with various
      MR sequences including diffusion-weighted echo-planar imaging.
AB  - OBJECTIVE: To assess the diagnostic accuracy of MR imaging for detecting bone
      marrow infiltration by malignant lymphoma. PATIENTS AND DESIGN: Fifty-three
      patients with malignant lymphoma underwent MR imaging and bone marrow biopsy. In
      80 iliac crests of the 53 patients (13 positive specimens in 9 patients and 67
      negative specimens in 44 patients), biopsy results and the signal intensity
      characteristics were compared. MR sequences included T1-weighted SE, T2-weighted
      FSE with fat suppression, FSE STIR, and diffusion-weighted EPI with fat
      suppression at 1.5 T. RESULTS AND CONCLUSIONS: To detect lymphoma infiltration,
      T1-weighted SE had the highest sensitivity (92%) and diffusion-weighted EPI with
      fat suppression and FSE STIR had the highest specificity (92.5% and 92%,
      respectively). A combination of T1-weighted SE and FSE STIR yielded the highest
      sensitivity and specificity (85% and 97%, respectively). A combination of T1
      weighted SE and FSE STIR sequences seems to be the current choice of imaging
      protocol for detecting bone marrow infiltration by malignant lymphoma.

PMID- 11981603
TI  - Quantitative ultrasound in the assessment of bone status of patients suffering
      from rheumatic diseases.
AB  - OBJECTIVE: To explore the effects of rheumatic diseases and glucocorticoids on
      bone mass a group of patients suffering from systemic lupus erythematosus (SLE,
      n=18) and rheumatoid arthritis (RA, n=22) were examined. DESIGN: We examined 40
      patients and 48 controls with quantitative ultrasound (QUS) and dual-energy X-ray
      absorptiometry (DXA). RESULTS: QUS (broadband ultrasound attenuation, BUA; speed
      of sound, SOS) values were found to be significantly lower in patients than in
      controls ( P<0.001). QUS measurements were moderately correlated with DXA
      measurements (kappa score ( kappa) 0.28 at the lumbar spine, and 0.46 at the
      femoral neck). There were no significant relations between the dosage of
      glucocorticoids and QUS parameters. CONCLUSION: In patients suffering from
      inflammatory rheumatic diseases QUS values were significantly decreased. SOS but
      not BUA and DXA measurements reflected disease activity assessed by erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP). QUS reflects different
      aspects of bone status compared with DXA.

PMID- 11981604
TI  - Acetabular stress fractures in military endurance athletes and recruits:
      incidence and MRI and scintigraphic findings.
AB  - OBJECTIVE: To evaluate the incidence and the MRI and scintigraphic appearance of
      acetabular stress (fatigue) fractures in military endurance athletes and
      recruits. DESIGN AND PATIENTS: One hundred and seventy-eight active duty military
      endurance trainees with a history of activity-related hip pain were evaluated by
      both MRI and bone scan over a 2-year period. Patients in the study ranged in age
      from 17 to 45 years. They had hip pain related to activity and had plain
      radiographs of the hip and pelvis that were interpreted as normal or equivocal.
      The study was originally designed to evaluate the MRI and scintigraphic
      appearance of femoral neck stress fractures. Patients had scintigraphy and a
      limited MRI examination (coronal imaging only) within 48 h of the bone scan.
      Twelve patients demonstrated imaging findings compatible with acetabular stress
      fractures. RESULTS: Stress fractures are common in endurance athletes and in
      military populations; however, stress fracture of the acetabulum is uncommon.
      Twelve of 178 patients (6.7%) in our study had imaging findings consistent with
      acetabular stress fractures. Two patterns were identified. Seven of the 12 (58%)
      patients had acetabular roof stress fractures. In this group, two cases of
      bilateral acetabular roof stress fractures were identified, one with a
      synchronous tensile sided femoral neck stress fracture. The remaining five of 12
      (42%) patients had anterior column stress fractures, rarely occurring in
      isolation, and almost always occurring with inferior pubic ramus stress fracture
      (4 of 5, or 80%). One case of bilateral anterior column stress fractures was
      identified without additional sites of injury. CONCLUSIONS: Stress fractures are
      commonplace in military populations, especially endurance trainees. Acetabular
      stress fractures are rare and therefore unrecognized, but do occur and may be a
      cause for activity-related hip pain in a small percentage of military endurance
      athletes and recruits.

PMID- 11981605
TI  - Normal murine bone morphometry: a comparison of magnetic resonance microscopy
      with micro X-ray and histology.
AB  - OBJECTIVE: The authors have devised a means to assess subtle changes in the
      structure of bone using magnetic resonance (MR) microscopy. MR microscopy was
      compared with micro X-ray and histology to analyze the structure of normal bone.
      DESIGN: Femurs of C57Bl/6 mice were examined ex vivo using differently orientated
      slices and pulse sequences on both a 9.4 and 11.7 T MR scanner, followed by micro
      X-ray and histology. A thresholding analysis technique was applied to MR images,
      to generate contour lines delineating the boundaries between bone and marrow.
      RESULTS: By MR microscopy, optimal correlation with histological "gold standards"
      was obtained using a longitudinal sectional versus a cross-sectional slice
      profile, a short echo time gradient-echo sequence versus a long echo time spin
      echo sequence, and a higher field strength, 11.7 T versus 9.4 T. Gradient-echo
      images at 11.7 T were acquired with a maximum in-plane resolution of 35 microm.
      CONCLUSION: Our results demonstrate that the percent area of marrow increases and
      percent area of trabecular bone and cortical bone thickness decreases on moving
      from the epiphyseal growth plate to the diaphysis. These changes observed with MR
      microscopy correlate with the histological data, but did not correlate with micro
      X-ray data, which showed no trends. Our quantitative evaluation using MR
      microscopy was found to be an effective means to visualize the normal variation
      in bone microanatomy compared with a histological "gold standard", and was a
      superior means of quantification in comparison with micro X-ray.

PMID- 11981606
TI  - MR imaging of meniscal malformations of the knee mimicking displaced bucket
      handle tear.
AB  - We report two cases of patients with lateral meniscal malformations of the knee
      that were found incidentally. Magnetic resonance imaging (MRI) of both cases
      showed a fragment-like meniscus structure located in the intercondylar notch,
      very similar to the "fragment in the intercondylar notch sign" observed in
      displaced bucket-handle tear. Arthroscopic examinations revealed a ring-shaped
      lateral meniscus in one case, and "flipped-over" lateral meniscus in the other.
      In the latter, a similar lateral meniscal malformation was observed
      contralaterally at MR arthrography.

PMID- 11981607
TI  - Extraskeletal myxoid chondrosarcoma arising in the finger.
AB  - Extraskeletal myxoid chondrosarcoma (EMCS) is a rare soft tissue sarcoma and
      usually occurs in deep soft tissues, especially of the proximal extremities and
      limb girdles. We present an unusual case of the tumor arising in the finger. The
      diagnosis was confirmed by molecular detection of a characteristic EWS-CHN/TEC
      fusion gene transcript. Molecular detection of the tumor specific fusion gene
      could be a valuable aid for the final diagnosis of EMCS, particularly in cases
      with unusual clinicopathological features.

PMID- 11981608
TI  - MRI of Gorham's disease: findings in two cases.
AB  - Gorham's disease is a rare condition characterized by non-malignant proliferation
      of vascular or lymphatic structures of bone resulting in progressive bony
      destruction and often extending into surrounding soft tissues. We present two
      cases of MR imaging findings of Gorham's disease involving the axial and
      appendicular skeleton with a 10-year follow-up in one patient. MR imaging
      findings in this entity are reviewed.

PMID- 11981609
TI  - Focal myositis of the thigh: unusual MR pattern.
AB  - Focal myositis is a commonly referenced, infrequently reported and poorly
      documented benign inflammatory pseudotumor which may be misdiagnosed clinically
      as a malignant tumor. We report the clinicopathologic features and magnetic
      resonance imaging findings in a case of focal myositis in the thigh of a 55-year
      old woman. A different radiologic presentation of this disorder is described. The
      gross appearance of the lesion, previously undescribed, appears to be rather
      specific for such a pseudoneoplastic disorder, and correlates very well with the
      magnetic resonance imaging features.

PMID- 11981610
TI  - Post-traumatic and stress-induced osteolysis of the distal clavicle.

PMID- 11981612
TI  - ePTFE-covered stent-grafts for revision of obstructed transjugular intrahepatic
      portosystemic shunt.
AB  - PURPOSE: To determine whether transjugular intrahepatic portosystemic shunt
      (TIPS) revisions with the Hemobahn stent-graft or the Viatorr endoprosthesis
      increase secondary patency rates. METHODS: Between 1998 and June 1999, Hemobahn
      endoprostheses (W.L. Gore, Flagstaff, AZ, USA) were used for the revision of
      obstructed TIPS in seven patients, 51-67 years of age (mean 59 years). From June
      1999 to 2000, the Viatorr endoprosthesis (W.L. Gore, Flagstaff, AZ, USA) was used
      for revision of obstructed TIPS in nine patients, 33-64 years of age (mean 49
      years). Follow-up included duplex ultrasound, clinical assessment and venous
      portography. RESULTS: The technical success rate of TIPS revision with the
      Hemobahn stent-graft was 100%. The pressure gradient decreased from a mean of 20
      mmHg to 10 mmHg. The mean follow-up was 407 days (range 81-868 days). In two
      patients TIPS occlusion occurred at 62 and 529 days after stent-graft placement,
      respectively; in another two patients outflow tract stenosis occurred at 275 and
      393 days, respectively. The technical success rate of TIPS revision with the
      Viatorr endoprosthesis was also 100%. The pressure gradient decreased from a mean
      of 27 mmHg to 11 mmHg. At a mean follow-up of 201 days (range 9-426 days), all
      Viatorr endoprostheses are still patent without in-graft stenosis, but
      angioplasty was required in two patients to treat a portosystemic pressure
      gradient > 15 mmHg. Four of the nine patients in the Viatorr group suffered from
      new encephalopathy after TIPS revision. CONCLUSION: The Viatorr endoprosthesis
      yielded optimal results with 100% in-graft patency rates at follow-up but had a
      high incidence of new encephalopathy, whereas the use of Hemobahn stent-graft for
      TIPS revision did not appear to improve the secondary patency rates in our
      series.

PMID- 11981613
TI  - Tribute to Folke Skoog: Recent Advances in our Understanding of Cytokinin
      Biology.

PMID- 11981614
TI  - The management of immediate post-traumatic seizures in children following minor
      head injury--time for a multi-center study?

PMID- 11981615
TI  - Composite type of split cord malformations.

PMID- 11981616
TI  - Telomerase in brain tumors.
AB  - INTRODUCTION: In recent years, many scientists involved in cancer research have
      directed their attention to telomerase, an enzymatic complex which is
      specifically involved in duplicating telomeres, the very ends of linear
      chromosomes. The discovery that most immortal cell lines in vitro and human tumor
      cells in vivo have telomerase activity, in contrast to telomerase-negative normal
      somatic cells, has made telomerase a candidate for use as a molecular marker of
      malignancy and even as a target for anticancer therapies. Thus, the assessment of
      the role of telomerase activity in neoplastic transformation has become a key
      issue in oncology, as stated by the exponential increase of papers on telomerase
      in the last 5 years. OBJECT: In this paper, we review some recent data from the
      literature, including our own studies, on the regulation of telomerase activity
      in brain tumors.

PMID- 11981617
TI  - Tuberculous brain abscess: clinical presentation, pathophysiology and treatment
      (in children).
AB  - BACKGROUND: Tubercular brain abscess (TBA) is a rare manifestation of CNS
      tuberculosis. It is characterised by an encapsulated collection of pus,
      containing viable tubercular bacilli without evidence of tubercular granuloma.
      PRESENTATION AND HISTORY: Patients may present with features of raised
      intracranial pressure and focal neurological deficit commensurate with the site
      of the abscess. A history of pulmonary tuberculosis may be present, as documented
      in one of our six cases; three of our six children developed TBA despite 3-weeks
      to 12-month courses of antitubercular chemotherapy prescribed for post-TBM
      hydrocephalus. DIAGNOSIS: Contrast CT head, MRI, MR spectroscopy is helpful in
      making the diagnosis and planning the treatment. TBA may be unilocular or
      multilocular on contrast CT scan. A relatively long clinical history and an
      enhancing capsule with thick wall are suggestive of TBA. Pyogenic abscess,
      however, has a thin rim on contrast CT. The capsule of TBA is formed of vascular
      granulation tissue containing acute and chronic inflammatory cells, particularly
      polymorphs. Proof of tubercular origin must be demonstrated either by presence of
      acid fast bacilli in culture or staining of pus or wall. TREATMENT: Treatment
      options include simple puncture, continuous drainage, fractional drainage,
      repeated aspiration through a burr hole, stereotactic aspiration and total
      excision of the abscess. Total excision usually becomes necessary in multilocular
      noncommunicating and thick-walled abscesses. Antitubercular therapy is the
      mainstay of management. The development of fulminant tubercular meningitis is
      sometimes problematic following surgical excision of TBA, as seen in one of our
      four operated cases. Mortality is reported to be high despite progress in
      treatment, while five of the six children treated by us responded well to the
      treatment.

PMID- 11981618
TI  - Changes in cerebral hemodynamics assessed by transcranial Doppler ultrasonography
      in children after head injury.
AB  - INTRODUCTION: Head injury is an important factor in children's morbidity and
      mortality. Arterial vasospasm and probably resulting from this, delayed ischemic
      deficit are important sequels of head trauma with detrimental effects on outcome.
      These problems have already been well studied in adults, but not in children. The
      noninvasiveness and ease in use of transcranial Doppler ultrasound technique
      (TCD) make it an ideal tool for the assessment of changes in cerebral circulation
      not only for the purposes of diagnosis but also for follow-up. PATIENTS AND
      METHODS: The authors review the present literature and analyze the usefulness of
      TCD as used in a group of 27 head-injured children aged 3-16 years. GCS/CCS
      score, CT pictures and neurological status were estimated. TCD examination was
      performed on the 2nd day after injury and each of the following 5 days or until
      normalization of flow velocities. Blood flow velocity was measured in the middle
      cerebral artery, the anterior cerebral artery and the extracranial portion of the
      internal carotid artery. The pulsatility index was also read. RESULTS: A
      significant correlation was found between changes in blood flow parameters and
      neurological status. High blood flow velocities seemed to be caused by hyperemia
      rather than by vasospasm. CONCLUSION: The results confirm that TCD is a useful
      method in the management of children after head injury.

PMID- 11981619
TI  - Prognostic factors and outcome of children with severe head injury: an 8-year
      experience.
AB  - OBJECTIVES: Our aim was to analyze prognostic factors and their association with
      outcome among children with severe head injury. METHODS: We conducted a
      retrospective study among children with severe head injury admitted to our
      Pediatric Intensive Care Unit (PICU) from November 1992 to December 2000. The
      patients were immediately evaluated for the severity of head injury (Glasgow Coma
      Score, GCS), clinical presentation, cerebral axial tomography, early
      complications (hypoxia and hypotension), metabolic and hematological alterations
      and early post-traumatic seizures. Six months after injury we applied the Glasgow
      Outcome Score (GOS). Correlations with GOS were evaluated using univariate and
      multivariate logistic models. RESULTS: In all, 122 children with severe head
      injury were identified. The patients presented the following scores: 18 (14.7.0%)
      children had a GOS of 1; 2 had a GOS of 2 (1.6%); 27 (22.2%) a GOS of 3 and 75
      (61.5%) a GOS of 4 or 5. A low GOS was significantly and independently associated
      with low GCS, multiple trauma, the presence of hypoxia and hypotension,
      disseminated intravascular coagulation (DIC), hyperglycemia and early post
      traumatic seizures. Hematological alterations (white blood cells) were also
      associated with a low GOS, though not significantly. CONCLUSION: In addition to
      GCS, types of trauma and brain lesion, hypoxia and hypotension, hemocoagulative
      disorders (DIC), hyperglycemia and early post-traumatic seizures are predictors
      of GOS. A knowledge of these prognostic factors and the correct management of
      children with severe head injury helps clinicians to improve outcome and to
      reduce morbidity and mortality.

PMID- 11981620
TI  - Vascular endothelial growth factor and erythropoietin concentrations in
      cerebrospinal fluid of children with hydrocephalus.
AB  - INTRODUCTION: Hypoxia induces transcription of vascular endothelial growth factor
      (VEGF) and erythropoietin (EPO) genes. We set up the hypothesis that elevated
      intracranial pressure in patients with hydrocephalus triggers release of VEGF and
      EPO into cerebrospinal fluid (CSF). METHODS AND RESULTS: VEGF and EPO
      concentrations, measured in 57 CSF aliquots obtained from infants and children
      with hydrocephalus undergoing surgery or therapeutic taps, were significantly
      elevated compared with those in 41 CSF aliquots of sex- and age-matched children
      undergoing routine diagnostic lumbar puncture for unrelated reasons ( P<0.001 and
      P=0.015, respectively). In hydrocephalus samples, median (interquartile range)
      VEGF concentrations were 135 (35-410) pg/ml, and 4 of 57 hydrocephalus samples
      had a VEGF concentration below the detection limit (1 pg/ml), compared with 38 of
      41 control samples. Erythropoietin was undetectable (<0.1 pg/ml) in 34 of 57
      hydrocephalus samples and in 34 of 41 controls. CONCLUSION: We conclude that
      conditions necessitating surgical intervention in hydrocephalus patients result
      in increased CSF concentrations of VEGF and EPO.

PMID- 11981621
TI  - Utility of transcranial Doppler ultrasonography in the diagnosis and follow-up of
      tuberculous meningitis-related vasculopathy.
AB  - INTRODUCTION: This prospective clinical study tested the hypothesis that
      transcranial Doppler ultrasonography (TCD) can be efficiently utilized in the
      diagnosis and management of tuberculous meningitis-related vasculopathy. PATIENTS
      AND METHODS: Twenty patients with tuberculous meningitis were assessed with
      serial TCD examinations. Blood flow velocity (Vm) and pulsatility index (PI) were
      measured, and findings were correlated with patient prognosis and with clinical
      and radiological findings. RESULTS AND CONCLUSIONS: The TCD data allowed us to
      distinguish three phases of tuberculous meningitis-related vasculopathy. In phase
      I vasculopathy TCD reveals increased Vm and normal to moderately decreased PI. In
      patients in this phase reversible ischemic deficits are seen clinically and
      radiologically. Phase II is associated with decreased Vm and decreased PI. At
      this stage patients reveal radiological and clinical signs related to proximally
      evolving vasculopathy in the basal main arteries. Phase III is characterized by
      almost absent blood flow in one or more basal arteries and, accordingly, by
      associated brain tissue infarction and permanent severe neurological deficit or
      fatal outcome.

PMID- 11981622
TI  - Neuroendoscopic intracranial pressure monitoring.
AB  - OBJECT: We wished to find a way of monitoring patients' intracranial pressure
      (ICP) during endoscopic surgery. METHODS: The Codman Microsensor ICP monitor can
      be inserted through the working channel of an endoscope with an interposed
      assembly (Check Flo II with male fitting, 9 F, manufactured by Cook, model #CFM
      100TM) to provide a water-tight seal and allow simultaneous irrigation. During
      endoscopic third ventriculostomy surgery with this setup in our hospital, the ICP
      was continuously monitored. The effects of irrigation on ICP were also followed.
      The sensor was assumed to be absolutely accurate and not referenced to a column
      of water. CONCLUSION: The small size of the Microsensor ICP monitor enabled easy
      placement through the working channel of the endoscope and interposed assembly.
      The ICP reading was continuously available, even during irrigation. The effect of
      irrigation on ICP was carefully monitored, and limited when pressure changes were
      noted.

PMID- 11981623
TI  - Localization of congenital glioblastomas in the Japanese: a case report and
      review of the literature.
AB  - We report a rare case of glioblastoma that was definitely congenital. Most
      congenital glioblastomas arise in the cerebral hemispheres. Four cases of
      congenital glioblastoma have been reported in the literature from Asian
      countries, two from Japan and the others from Korea. Two Japanese cases arose in
      the cerebello-pontine angle, and a cerebellar hemisphere, respectively. In
      contrast, both known Korean cases and Euro-American cases arose in cerebral
      hemispheres. Surprisingly, the parents of the present patient were Korean. When
      we reviewed the world literature on congenital glioblastomas, we recognized that
      in Japanese patients this tumor did not tend to occur in a cerebral hemisphere.
      This deviation of the localization may have biological reasons, such as genetic
      or environmental factors.

PMID- 11981624
TI  - Isolated meningeal chloroma (granulocytic sarcoma) in a child with acute
      lymphoblastic leukemia mimicking a falx meningioma.
AB  - BACKGROUND: Isolated chloromas (granulocytic sarcomas) are rare tumors. Chloromas
      are masses composed of immature granulocytic cells. Granulocytic sarcoma occurs
      primarily in patients with acute myelogenous leukemia, but can also arise in
      patients with other myeloproliferative disorders, though rarely in patients with
      acute lymphoblastic leukemia (ALL). When dural-based, granulocytic sarcoma may be
      indistinguishable from meningioma radiologically. CASE HISTORY: We now describe
      one patient affected by ALL with isolated granulocytic sarcoma mimicking
      meningioma as initial CNS relapses. A 12-year-old girl who had been diagnosed
      with ALL and undergone chemotherapy presented with generalized tonic-clonic
      seizure while in complete remission. Computed tomographic scan and magnetic
      resonance imaging showed a small mass mimicking a meningioma at the anterior
      falx. The patient was developed speech disturbance 6 days later. Follow-up
      magnetic resonance imaging demonstrated a rapidly growing mass with intralesional
      hemorrhage. Bone marrow biopsy and cerebrospinal fluid study were negative for
      leukemia. The patient underwent open surgery. The pathological diagnosis was
      acute lymphoblastic leukemia. CONCLUSIONS: These unusual clinical manifestations
      and radiological findings in acute lymphoblastic leukemia should be regarded as a
      recurrence of leukemia. Early detection and antileukemic treatment of
      granulocytic sarcoma are necessary and important for a favorable prognosis.

PMID- 11981625
TI  - Detection of a pineoblastoma with large central cyst in a young child.
AB  - THE PATIENT: We present the very rare case of a pineoblastoma with large central
      cyst in a 7-year-old boy who presented with a short history of gradually
      worsening headache and upward gaze palsy. IMAGING INVESTIGATIONS: On CT and MRI
      studies, it was seen as a peripherally calcified, irregularly shaped mass with
      heterogeneous low signal intensity on T1-weighted images and ringed enhancement
      after gadolinium administration; there was homogeneous high signal intensity on
      T1-weighted images. DISCUSSION: We discuss differential diagnosis for several
      types of cystic tumors in the pineal region, including pineoblastomas.

PMID- 11981626
TI  - Osteoid osteoma -- a rare cause of brachial neuralgia.
AB  - BACKGROUND: Osteoid osteoma of the spine causing brachial neuralgia is rare.
      OBJECT: An adolescent with cervicobrachial neuralgia due to osteoid osteoma of C
      4 is presented, and the relevant literature reviewed. CONCLUSION: The possibility
      of osteoid osteoma of the cervical spine should be entertained in the
      differential diagnosis of brachial neuralgia in adolescents.

PMID- 11981627
TI  - Rapid enlargement of a residual craniopharyngioma during short-term growth
      hormone replacement.
AB  - CASE REPORT: A patient with residual craniopharyngioma experienced a rapid tumor
      relapse during growth hormone therapy. OBJECTIVE: We present this case and remind
      physicians that it is necessary to reevaluate the safety of growth hormone
      therapy in patients with residual craniopharyngioma.

PMID- 11981628
TI  - A case of intracranial arteriovenous fistula in an infant with neurofibromatosis
      type 1.
AB  - INTRODUCTION: Reported cases of arteriovenous fistula (AVF) with
      neurofibromatosis type1 (NF1) are rare. CASE REPORT: In this paper we report the
      first case of intracranial AVF in an NF1 infant who developed heart failure.
      Endovascular treatment using coils successfully obliterated the AVF. The
      mechanism underlying the AVF in this case was believed to be a congenital
      mesenchymal abnormality of the intracranial vessels. DISCUSSION: The mechanism
      underlying the development of heart failure in this case is also discussed.

PMID- 11981629
TI  - Metastatic spinal cord compression of testicular yolk sac tumor.
AB  - INTRODUCTION: Pediatric testicular tumors are rare. Spinal metastasis of
      testicular yolk sac tumor (YST) is extremely rare, with only one reported case.
      CASE REPORT: We report a rare case of metastatic spinal cord compression of
      testicular YST in a 14-month-old boy who presented with progressive paraparesis
      and neurological bladder dysfunction. Two months prior to admission, he underwent
      a left radical orchiectomy for YST of the testis. Magnetic resonance imaging
      revealed severe spinal cord compression by the ventral epidural mass from T-9 to
      T-11 and at S-3. Emergency surgical resection was performed for tissue diagnosis
      and spinal decompression. Histopathological features of the epidural mass
      indicated metastasis of the testicular YST. CONCLUSION: Although spinal
      involvement with metastatic YST is rare, it must be considered in children with
      testicular YST exhibiting evidence of pain or weakness, and surgical
      decompression followed by adjuvant chemotherapy should not be delayed.

PMID- 11981630
TI  - Mild hypothermia for hemispheric cerebral infarction after evacuation of an acute
      subdural hematoma in an infant.
AB  - The use of mild hypothermia to treat hemispheric infarction after evacuation of
      an acute subdural hematoma in an infant is reported. The patient, a 2-year-old
      boy, presented with a deteriorating level of consciousness after a fall from a
      tree. Computed tomography (CT) scan revealed an acute subdural hematoma on the
      right side with marked midline shift, and emergency evacuation of the hematoma
      was performed. The postoperative course was uneventful until the patient's
      intracranial pressure (ICP) rose and his condition deteriorated 3 days after
      surgery. CT scan revealed a hemispheric infarction on the injured side. Mild
      hypothermia was induced to control the ICP and protect the brain. While the
      hypothermia was effective in lowering the elevated ICP, it failed to arrest
      progression of the infarction. The patient was discharged with mild disability 2
      months after the injury. No serious complications occurred during or after the
      hypothermia. Our experience indicates that hypothermia can be a useful procedure
      for controlling the ICP in children with severe traumatic brain injury including
      acute subdural hematoma, although its capability to protect the brain from
      severe, progressive ischemia appears to be limited.

PMID- 11981631
TI  - CSF hydrothorax--VP shunt complication without displacement of a peritoneal
      catheter.
AB  - Cerebrospinal fluid hydrothorax is reported as a rare complication of
      ventriculoperitoneal (VP) shunt. A 16-month-old boy known to have congenital
      hydrocephalus and a Dandy-Walker cyst presented with serious respiratory
      distress. Examination revealed right pleural effusion and congested throat.
      Thoracocentesis with drainage of the pleural cavity for 10 days failed to free
      the patient from pleural effusion. Following an intraperitoneal injection of
      Omnipaque a chest X-ray was done, and samples of pleural fluid taken before and
      after the injection were compared on X-ray, revealing the presence of contrast in
      the postinjection pleural effusion. Changing the VP shunt for a ventriculo-atrial
      shunt resulted in immediate (within 1 day) complete disappearance of the pleural
      effusion and of the patient's chest symptoms. Probable causes of this rare
      complication are discussed, and attention is drawn to the possibility of its
      appearance and early recognition. Intraperitoneal injection of contrast material
      followed by X-ray examination of fluid in the chest is a simple, safe, and
      reliable method of diagnosis when it is suspected.

PMID- 11981632
TI  - A rare case of shunt malfunction attributable to blockage of a Codman-Hakim
      programmable shunt valve.
AB  - BACKGROUND: We report a rare case of shunt malfunction resulting from blockage of
      a Codman-Hakim programmable shunt valve by fibrinoid-like tissues. HISTORY: The
      patient had undergone shunt system placement for hydrocephalus after hemorrhagic
      infarction at the age of 8 months; a Codman-Hakim programmable shunt valve was
      used at that time. LATER COURSE: Two years after shunt placement, the boy
      suffered from irritability and poor activity when the aforementioned shunt
      malfunction arose following valve blockage by fibrinoid-like tissues. He
      underwent shunt revision and was subsequently free of symptoms.

PMID- 11981633
TI  - Alagille syndrome associated with angiographic moyamoya.
AB  - We describe the case of a 13-year-old boy with Alagille syndrome in whom
      intracranial imaging was performed following a seizure. The MRI and MRA revealed
      changes of angiographic moyamoya within both the anterior and posterior
      circulation. This very rare manifestation of the systemic vasculopathy in
      Alagille syndrome has not been previously documented in a patient without a focal
      neurological deficit. We discuss the potential role of routine intracranial
      imaging in patients with Alagille syndrome.

PMID- 11981634
TI  - Myelopathy caused by tics in an adolescent, associated with T2 signal intensity
      changes of the spinal cord.
AB  - COURSE: A 15-year-old boy who had suffered motor tics since age 9 developed
      progressive cervical myelopathy involving both his hands and his lower
      extremities. T2-weighted MRI revealed mild canal stenosis and increased signal
      intensity in the cervical spinal cord beginning at the C-4 level and continuing
      upward to the medulla oblongata. TREATMENT: After C-3 to C-7 laminoplasty, the
      patient's clinical symptoms improved. DISCUSSION: It is possible that movement
      disorders such as tics may contribute to the development of cervical myelopathy
      owing to the effects of involuntary movements on the neck. Such an intensity
      change on a T2-weighted image has never been reported in an adolescent tic
      disorder. Despite such changes, surgical treatment may bring about clinical
      improvement.

PMID- 11981637
TI  - "Do you, doctor, take the mfERG.for better or for worse?".

PMID- 11981638
TI  - Monitoring retinal function in neovascular maculopathy using multifocal
      electroretinography - early and long-term correlation with clinical findings.
AB  - PURPOSE: To objectively investigate and longitudinally monitor retinal function
      in patients with choroidal neovascularization (CNV) due to exudative age-related
      macular degeneration (AMD) and myopia using multifocal electroretinography
      (mfERG). METHODS: Patients with classic and occult subfoveal CNV secondary either
      to AMD or to myopia were enrolled in the study. The mfERGs were performed at the
      beginning of the study and every 3 months subsequently during a follow-up period
      of 15 months. In addition, standardized visual acuity testing, ophthalmologic
      examinations, color fundus photographs and fluorescein angiography were
      performed. The mfERG records were derived with the VERIS-System (Electro
      Diagnostic Imaging, San Mateo, Calif., USA); 103 locations within the central 50
      degrees in diameter were stimulated concurrently by means of the m-sequence
      technique. Fixation stability was monitored throughout the recording session with
      an infrared eye monitoring system (VERIS Refractor/Camera unit). The first-order
      response component was extracted for each stimulated retinal location. The
      response densities of the first-order kernel were evaluated as a function of
      eccentricity from the center (ring 1) to the periphery of the stimulated area
      (ring 6). The results were compared to those derived from age-matched normal
      control groups. For each patient mfERG responses measured on follow-up visits
      were compared to each other to evaluate and monitor changes in retinal function.
      These changes were tested for correlation with those observed in other clinical
      and electroretinographic findings. Statistical analysis was performed using the
      Pearson coefficient. RESULTS: Subfoveal neovascular maculopathy was associated
      with a reduction in response density most prominent within the central 5 degrees
      over the area affected by CNV detected either at the beginning of the study or at
      the follow-up recordings. During the follow-up period patients 1 and 4 showed
      stabilization or a slight increase in response densities over the neovascular
      lesion-complex and a corresponding stabilization or slight increase in visual
      acuity accompanied by a decrease in the activity of the neovascular lesion as
      determined by fluorescein angiography. Patient 2 revealed an increase in response
      density correlating with an increase in visual acuity and decrease in lesion
      size. In the contralateral eye of this patient the response density dropped in
      the area of new subfoveal CNV. In patient 3 continuous progression of the disease
      was documented by fluorescein angiography and visual acuity. It correlated well
      with a continuous decrease in retinal response densities during the follow-up.
      CONCLUSIONS: Objective monitoring of retinal function and correlation with
      morphological and psychophysical findings was at least in part possible in
      patients suffering from AMD and myopia. In all of four patients whose subfoveal
      CNV was documented by fluorescein angiography. Response densities were reduced
      particularly in the central 5 degrees and in visual acuity. The mfERG data showed
      a moderate to high statistical correlation with visual function as measured by
      visual acuity. On the other hand, the greatest linear dimension of the lesion
      size showed only a weak to moderate statistical correlation with both the
      response densities of the mfERG and the visual acuity. We conclude that the size
      of the CNV complex does not represent an accurate measure of retinal function in
      neovascular maculopathy. The good correlation of the mfERG data with visual
      acuity suggests that it may serve for objective assessment of retinal function,
      of the areas overlying the CNV. It shows potential as a valuable tool for
      longitudinal monitoring of AMD patients.

PMID- 11981639
TI  - Internal and external contamination of donor corneas before in situ excision:
      bacterial risk factors in 93 donors.
AB  - BACKGROUND: Most studies of corneal donor contamination concentrate on
      postenucleation contamination of the eyeball. The purpose of the present study
      was to evaluate the relative contamination of in situ excised corneal tissue and
      relevance to final success or rejection by recipients of the corneal grafts.
      METHODS: Ninety-three donors underwent anterior chamber puncture (ACP) and
      corneal epithelium scarification (CS) before and after disinfection with 5%
      povidone-iodine. Following in situ excision, corneas were preserved in culture
      medium at +35 degrees C. Morphological and bacteriological assessment was carried
      out after culture, and recipients were followed up over a 2-year period. RESULTS:
      Samples taken by ACP, CS before disinfection, CS after disinfection and a culture
      medium sample were contaminated by bacteria in, respectively, 8 (8.6%), 23
      (24.7%) 4 (4.3%) and 5 (5.4%) donors. Contamination of aqueous humor was
      significantly associated with age, death-to-sample time and premortem systemic
      infection. Contamination of epithelium significantly increased culture medium
      contamination. CONCLUSION: External bacteria on donor cornea are mainly skin
      bacteria (especially Staphylococcus) and can be partially eliminated by a
      povidone-iodine wash. Internal bacteria are mainly gut bacteria and may be due to
      perimortem bacteriemia. However, bacterial infection at the time of death appears
      to have no effect on the incidence of endophthalmitis in recipients and should no
      longer prevent use of such corneal tissue in grafts.

PMID- 11981640
TI  - Electron microscopic and immunohistochemical examination of scarred human cornea
      re-treated by excimer laser.
AB  - PURPOSE: To elucidate differences, at the macromolecular level, in corneal tissue
      subjected to repeated argon fluoride excimer treatment. METHODS: A light
      microscopic, electron microscopic, and immunohistochemical study was performed on
      a scarred human cornea. RESULTS: Keratocytes were enlarged with an expanded
      endoplasmic reticulum and exhibited a fibroblastic appearance. Amorphous material
      was observed extracellularly. Collagen fibrils exhibited a disordered arrangement
      while banding patterns and diameter were normal. Immunohistochemical
      investigation of several collagen types, of collagen-associated proteoglycans,
      and of basement membrane components demonstrated an enhanced immunoreactivity of
      all of them in the scarred area. Type V collagen was found as a normal component
      of the epithelial basement membrane whereas types I and III collagen were present
      beneath Bowman's layer. Excimer-laser-treated sections revealed considerably
      stronger subepithelial staining for collagen types I, III, IV, and V. Laminin-1,
      a typical component of basement membranes, was detectable throughout the scarred
      tissue. The small proteoglycans decorin and fibromodulin accumulated in a patch
      like manner in the scarred tissue below the epithelium, whereas biglycan was
      expressed by the epithelium and throughout the stroma. Lumican was expressed most
      strongly by the epithelium and rather equally distributed in the excimer-laser
      treated and in the normal stroma. CONCLUSION: Effects of argon laser treatment of
      the cornea must be regarded as a process acting over many months. Intra- and
      extracellular structures and components are involved and influence the
      unpredictable shape of the corneal architecture.

PMID- 11981641
TI  - Clinicopathologic correlation in hemorrhagic age-related macular degeneration.
AB  - PURPOSE: To analyze and compare the histopathology of surgically extracted
      membranes in hemorrhagic age-related macular degeneration (AMD) versus extracted
      classic, mixed and occult choroidal neovascularization (CNV) in AMD. METHODS:
      Thirty consecutive membranes, surgically removed in hemorrhagic AMD, were
      analyzed and compared with consecutive series of 50 classic, 20 mixed and 20
      occult membrane specimens in exudative AMD. The specimens were serially sectioned
      and stained in a stepped fashion with hematoxylin-eosin, Masson trichrome and
      periodic acid-Schiff stain. RESULTS: Diffuse drusen were observed in all
      hemorrhagic AMD specimens, fibrovascular tissue was found in 29 of 30 specimens
      which was located subretinally in 11 specimens and/or in Bruch's membrane in 28
      specimens. A hemorrhage was located subretinally in 21 specimens, in the stroma
      of the fibrovascular tissue in 17 specimens, at the choroidal side of the diffuse
      drusen adjacent to fibrovascular tissue in 13 specimens and at the choroidal side
      of the fibrovascular tissue in Bruch's membrane in 8 specimens. Grossly dilated
      thin-walled vessels were identified in one hemorrhagic AMD case, suggestive of
      polypoidal choroidal vasculopathy. Scarred tears of the retinal pigment
      epithelium were identified in two specimens. CONCLUSION: A large spectrum of
      histo-architectural lesions is recognized in hemorrhagic maculopathy. Hemorrhages
      do not only characteristically appear in the subretinal space or in the stroma of
      the neovascular tissue but also at the choroidal side of the diffuse drusen
      adjacent to the neovascular complex and at the choroidal side of the intra
      Bruch's fibrovascular tissue.

PMID- 11981642
TI  - Hyperhomocyst(e)inemia and MTHFR C677T genotypes in patients with central retinal
      vein occlusion.
AB  - BACKGROUND: Elevated plasma homocyst(e)ine is a major risk factor for venous
      thrombosis and cardiovascular disease. Homozygosity for the MTHFR C677T mutation
      and low plasma folate levels increase plasma homocyst(e)ine concentrations. The
      aim of this retrospective case-control study was to investigate a possible
      association between hyperhomocyst(e)inemia and central retinal vein occlusion.
      METHODS: Our study included 78 consecutive patients with central retinal vein
      occlusion and 78 control subjects, matched for age and sex. High-performance
      liquid chromatography (HPLC) with fluorescence detection was used to determine
      fasting plasma homocyst(e)ine concentrations. Plasma folate and vitamin B12
      levels were determined by immunological assays. Genotyping for the MTHFR C677T
      mutation was performed by polymerase chain reaction (PCR). RESULTS:
      Hyperhomocyst(e)inemia was defined by the 95th percentile of plasma
      homocyst(e)ine concentrations in the control group (=14.83 micromol/l). Thus 16
      patients with central retinal vein occlusion were diagnosed as
      hyperhomocyst(e)inemic, compared with three control subjects ( P=0.001). The odds
      ratio of hyperhomocyst(e)inemia for central retinal vein occlusion was 5.29 (95%
      CI 1.33-21.13). Mean plasma folate levels were significantly lower in patients
      than in controls (3.94+/-1.94 ng/ml vs. 5.69+/-2.09 ng/ml; P<0.001). Distribution
      of MTHFR C677T genotypes did not significantly differ between the two groups.
      CONCLUSIONS: Our study suggests that hyperhomocyst(e)inemia, but not the MTHFR
      C677T mutation, is associated with central retinal vein occlusion.

PMID- 11981643
TI  - Outbreak of Empedobacter brevis endophthalmitis after cataract extraction.
AB  - BACKGROUND: We present a series of patients who were operated upon on the same
      day by the same surgeon. All of those patients developed postoperative
      endophthalmitis due to Empedobacter brevis - a bacterium hitherto unknown in
      ophthalmologic literature. METHODS: Twelve patients were referred because of
      endophthalmitis after cataract extraction. The patients' files were studied and
      the intraoperative and postoperative outcome was analysed. RESULTS: Twelve
      patients (five male, seven female, mean age 75 years) presented 1-6 days after
      uncomplicated cataract extraction. Although some suffered from medical or
      ophthalmological diseases there was no association with the severity of the
      endophthalmitis. Eleven patients required vitrectomy, seven as primary procedure,
      one primary with extraction of the lens and three secondary after anterior
      chamber lavage and intravitreal antibiotics. In three cases vitrectomy had to be
      repeated together with extraction of the intraocular lens. There were two
      postoperative retinal detachments that required silicon oil and in one case an
      encircling band. Mean visual acuity rose from 0.02 to 0.47 by 9 months after
      operation. Empedobacter brevis was found in the anterior chamber and in the
      vitreous in all except one patient. CONCLUSION: In high-volume cataract surgery
      endemic endophthalmitis is always possible. Sources of infection may be anything
      from the lens to the sterilisation process, the latter being the primary suspect
      in our series. Prompt, adequate and (if necessary) aggressive treatment by
      vitreous surgery may lead to favourable results.

PMID- 11981644
TI  - Advanced glycation end-products in corneas of patients with keratoconus.
AB  - BACKGROUND: Keratoconus remains a poorly understood yet widespread disease which
      poses a potential threat to human vision. The underlying mechanisms are still not
      clear. One possible pathway is increased formation and accumulation of advanced
      glycation end-products (AGEs) in the cornea. METHODS: Corneas obtained from six
      patients with keratoconus and from six healthy controls were investigated. An
      immunohistochemical localisation of the well-known AGE N(epsilon)
      carboxymethyllysine (CML) was performed using a polyclonal anti-CML antibody.
      RESULTS: In the corneas of all six patients with keratoconus, CML
      immunoreactivity was found in the epithelial as well as in the endothelial cells.
      The keratocytes also showed a positive reaction. The controls, in contrast,
      showed very little or no immunoreactivity. CONCLUSION: In the epithelial, stromal
      and endothelial cells of corneas with keratoconus an accumulation of CML was
      detected which might play a role in the pathogenesis of keratoconus.

PMID- 11981645
TI  - Visual outcome after allogenic penetrating keratoplasty.
AB  - PURPOSE: To evaluate visual outcome after allogenic penetrating keratoplasty.
      METHODS: The clinical non-randomized retrospective comparative interventional
      study included 245 patients undergoing allogenic penetrating keratoplasty for
      keratoconus ( n=77), herpetic corneal scars ( n=29), non-herpetic corneal scars (
      n=46), Fuchs endothelial dystrophy ( n=24), and pseudophakic/aphakic bullous
      keratopathy ( n=69). All patients were consecutively operated on by the same
      surgeon. The duration of follow-up had to exceed 1 year. RESULTS: Increase in
      visual acuity and the best-corrected postoperative visual acuity were
      significantly ( P<0.01) highest for the patients with keratoconus (visual acuity
      increase from 0.16 to 0.69), followed by those with herpetic corneal scars (from
      0.18 to 0.58), Fuchs corneal endothelial dystrophy (from 0.13 to 0.48), non
      herpetic corneal scars (from 0.13 to 0.36), and finally patients with
      pseudophakic/aphakic bullous keratopathy (from 0.05 to 0.28). The increase in
      visual acuity expressed in lines did not vary significantly ( P>0.05) among the
      study groups. Visual acuity increased significantly after suture removal, with no
      significant ( P>0.20) difference between the study groups. Visual acuity was
      significantly ( P<0.001) and positively correlated with the diameter of the
      corneal graft. Multiple linear regression analysis revealed that graft size,
      keratometric astigmatism and reason for keratoplasty were the major factors
      significantly ( P<0.05) influencing postoperative visual acuity. CONCLUSIONS: The
      main predictive factors for visual outcome after allogenic penetrating
      keratoplasty are reason for keratoplasty and graft size. Postoperative visual
      acuity is significantly the highest in keratoconus and significantly the lowest
      in pseudophakic/aphakic bullous keratopathy. Expressed in lines, increase in
      visual acuity does not differ significantly among groups of patients with
      different reasons for keratoplasty.

PMID- 11981646
TI  - Comparison of emergency eye-wash products in burned porcine eyes.
AB  - BACKGROUND: The long-term prognosis of patients with chemical eye burns depends
      on immediately rinsing the eye after the trauma. The chemical properties and
      tolerance of currently used rinsing solutions were examined. METHODS: NaCl 0.9%,
      Ringer lactate, balanced salt solution (Aqsia), phosphate buffer, tap water, and
      Previn were analyzed. The buffer capacities were determined by titration with HCl
      and NaOH. The osmolarity of the solutions and the osmolarity of 100 healthy and
      100 alkali burned porcine corneas were determined by means of freezing point
      depression. 56 enucleated porcine eyes were burned and rinsed with NaCl solutions
      of different osmolarities (0-1200 mosmol/l), Previn, NaCl 0.9% or phosphate
      buffer, respectively. The different swelling behaviors were determined by
      pachymetric measurements, and the resulting corneal osmolarity after irrigation
      was assessed. The effect of Previn as a hyperosmolar solution in comparison with
      isoosmolar phosphate buffer was examined on 10 healthy human eyes. RESULTS: Only
      phosphate buffer and Previn show high buffer capacities. The osmolarity of the
      healthy/burned porcine corneas was 329+/-61/1203+/-289 mosmol/kg. Except for
      Previn (862+/-3 mosmol/l), all solutions are hypo- or almost isoosmolar in
      comparison with the healthy cornea. Rinsing of the burned corneas causes swelling
      in all groups in inverse proportion to the osmolarity of the solution. Thus, the
      lower the solution's osmolarity, the stronger the swelling reaction of the
      cornea. The resulting corneal osmolarity following rinsing behaves proportionally
      to the osmolarity of the rinsing solution. Therefore, a high osmolarity of the
      rinsing solution correlates with a high corneal osmolarity. No long-term effects
      in healthy eyes were observed after rinsing with Previn or phosphate buffer.
      CONCLUSION: Corneal thickness and osmolarity are significantly correlated to the
      osmolarity of the rinsing solution. Corneal edema dilutes the agent in the
      stroma. Therefore, we recommend solutions with low osmolarity (tap water) or high
      buffer capacity (Previn) for the initial post-trauma irrigation.

PMID- 11981647
TI  - Oral administration of interferon-beta suppresses experimental autoimmune
      uveoretinitis.
AB  - BACKGROUND: The oral administration of type I interferons (IFNs) have been
      reported to reduce severity of inflammation in several animal models of
      autoimmune disease. This study examined whether oral administration of IFN-beta
      is capable of modulating inflammation in experimental autoimmune uveoretinitis
      (EAU). METHODS: EAU was induced in rats by immunization with interphotoreceptor
      retinoid-binding protein (IRBP) emulsified in complete Freund's adjuvant. Rats
      were treated with either varying doses (10(2), 10(3), 10(4) or 10(5)IU) of mouse
      recombinant IFN-beta or phosphate-buffered saline for control, via direct
      oropharyngeal application once a day for 28 days starting 7 days before IRBP
      immunization. Intraocular inflammation was assessed by slit-lamp biomicroscopy
      and histopathological examination. Spleen cell proliferation response and
      cytokine production under IRBP stimulation were assessed. Spleen cell
      subpopulations were also measured. RESULTS: IFN-beta at doses of either 10(4) or
      10(5) IU significantly reduced both the clinical and histopathological severity
      of EAU. Spleen cell proliferation and IFN-gamma production from rats treated with
      10(4) IU IFN-beta were significantly decreased compared with controls.
      Furthermore, the proportion of both NK cells and NKT cells in the spleen of rats
      treated with IFN-beta was increased compared with controls. CONCLUSION: These
      results suggest that the oral administration of IFN-beta reduces inflammation in
      IRBP-mediated EAU and that the mechanism of this action may involve NK cells and
      NKT cells.

PMID- 11981648
TI  - The effect of topical natural ergot alkaloids on the intraocular pressure and
      aqueous humor dynamics in rabbits with alpha-chymotrypsin-induced ocular
      hypertension.
AB  - BACKGROUND: We previously reported that topical natural ergot alkaloids
      ergocristine, alpha-ergocryptine and ergocornine dose-dependently reduce
      intraocular pressure in ocular normotensive rabbits, most likely by decreasing
      aqueous humor inflow. In the present study, the effects of these compounds on
      intraocular pressure and aqueous humor dynamics in a rabbit model for ocular
      hypertension were assessed. METHODS: Experiments were conducted in albino rabbits
      made ocular hypertensive by intracameral injection of alpha-chymotrypsin.
      Intraocular pressure responses to drug vehicle and seven different doses of
      topical natural ergot alkaloids were examined in order to obtain dose-response
      relationships for comparing the intraocular pressure-lowering effect and potency
      of these drugs. Tonographies were also performed to ascertain the actions of
      natural ergot alkaloids on aqueous humor dynamics in alpha-chymotrypsin-induced
      ocular hypertensive rabbits. RESULTS: Topical application of the natural ergot
      alkaloids ergocristine, alpha-ergocryptine and ergocornine lowered intraocular
      pressure in alpha-chymotrypsin-induced ocular hypertensive rabbits in a dose
      related fashion, with ergocristine displaying the greatest intraocular pressure
      lowering effect. Tonographic studies revealed a decrease in the tonographic
      outflow facility following topical application of natural ergot alkaloids,
      although only the effects of both ergocristine and alpha-ergocryptine reached
      statistical significance. All natural ergot alkaloids tested significantly
      reduced the calculated aqueous humor inflow. CONCLUSION: This study suggests that
      the natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine
      effectively decrease intraocular pressure in the alpha-chymotrypsin-induced model
      of ocular hypertension. Since these compounds reduce the tonographic aqueous
      humor outflow facility, their final ocular antihypertensive effect appears to
      result from a remarkable reduction of the aqueous humor inflow.

PMID- 11981649
TI  - Endophthalmitis caused by Moraxella osloensis.
AB  - PURPOSE: To report the clinical presentation, antibiotic sensitivities, and
      treatment outcomes of endophthalmitis caused by Moraxella osloensis. METHODS: 
      CASE SERIES: retrospective review of the medical records of all patients treated
      for endophthalmitis at Bascom Palmer Eye Institute between 1 January 1991 and 31
      December 2000. RESULTS: During the study interval, 757 eyes were treated for
      endophthalmitis. Moraxella osloensis was isolated from three eyes of two patients
      (3/757, or 0.39%). In all three eyes, the endophthalmitis was delayed-onset and
      bleb-associated; Moraxella osloensis was isolated on chocolate agar and 5%
      sheep's blood agar using a RapNH commercial Kit (by Remel) through an automated
      system (Vitek). Like most gram-negative organisms, Moraxella was sensitive to
      ceftazidime, ciprofloxacin, and the aminoglycosides. Although vision at
      presentation was poor, both patients regained baseline vision after treatment
      with pars plana vitrectomy and injection of intravitreal antibiotics.
      CONCLUSIONS: To our knowledge, this is the first report of endophthalmitis caused
      by Moraxella osloensis. Unlike most series of delayed-onset, bleb-associated
      endophthalmitis the visual prognosis following treatment for endophthalmitis
      caused by Moraxella osloensis appears to be generally favorable.

PMID- 11981652
TI  - Propylene glycol monomethyl ether occupational exposure. 3. Exposure of human
      volunteers.
AB  - OBJECTIVE: Propylene glycol monomethyl ether (PGME) is a widely used additive in
      industrial and consumer products (paints, inks, diluents, cleaning products,
      cosmetics.). The aim of the present study was to determine uptake and disposition
      of PGME alpha-isomer in humans. METHOD: Six healthy male volunteers were exposed
      to PGME-alpha vapour (15, 50 and 95 ppm) with and without respiratory protection
      for 6 h including a 30-min break. Free PGME and total PGME (free and conjugated)
      were analysed in urine. The analytical method involved hydrolysis with HCl (only
      for the analysis of total PGME in urine), a solid phase extraction on LC-18
      columns and a gas chromatograph-flame ionisation detector (GC/FID) analysis after
      derivatisation with trimethylsilylimidazole. RESULTS: End-exposure levels of free
      PGME in urine were found to reach 1.3 (+/-0.3), 4.4 (+/-1.6) and 7.9 (+/-2.5)
      mg/l for 15, 50 and 95-ppm exposure, respectively, without respiratory
      protection. End-exposure levels of total PGME in urine were found to reach 2.5
      (+/-0.8), 6.2 (+/-1.6) and 10.3 (+/-2.3) mg/l for 15, 50 and 95-ppm exposure
      respectively. Levels of free PGME were also monitored in exhaled air (0.4 (+/
      0.1), 1.4 (+/-0.4) and 2.9 (+/-0.9) ppm at the end of 15, 50 and 95-ppm exposure,
      respectively) and in blood (2.0 (+/-0.9), 4.9 (+/-2.3) and 11.8 (+/-2.4) mg/l at
      the end of 15, 50 and 95-ppm exposure, respectively). PGME is rapidly excreted in
      urine and in exhaled air; the half-lives were calculated to be approximately 3.5
      h in urine and 10 min in exhaled air. PGME was below detection limits in breath
      (<0.1 ppm), in blood (<1 mg/l) and in urine (<1 mg/l) after dermal-only exposure
      to vapour. CONCLUSIONS: This study has demonstrated the relatively high pulmonary
      uptake compared with the dermal uptake. It has also shown the rapid excretion in
      urine (3.5 h) and in expired air (10 min). With regard to metabolism, this study
      has established the presence of conjugated PGME in urine.

PMID- 11981653
TI  - Occupational respiratory hypersensitivity in dental personnel.
AB  - OBJECTIVE: The aim was to study the causes of respiratory hypersensitivity in
      dental personnel based on the statistics of the Finnish Register of Occupational
      Diseases (FROD; 1975-1998) and the patient material of the Finnish Institute of
      Occupational Health (FIOH; 1990-1998). METHODS: Details about the cases of
      respiratory hypersensitivity were compiled from the FROD. The occupational
      rhinitis diagnoses studied at the FIOH were based on work-related symptoms and a
      change in the status of the nasal mucosa during challenge testing; and the
      diagnosis of occupational asthma based on reactions in challenge testing, or on
      IgE positivity and peak flow monitoring at work and during days off. RESULTS: A
      total of 64 cases of occupational respiratory diseases (ORDs) was diagnosed in
      dental personnel during 1975 to 1998 according to the FROD; two cases in 1975 to
      1989, and 62 in 1990 to 1998. Twenty-eight cases were of occupational asthma (18
      caused by methacrylates), 28 occupational rhinitis (six caused by methacrylates),
      seven allergic alveolitis and one organic dust toxic syndrome (ODTS). The non
      acrylate-material diagnosed in 1990-1998 at the FIOH comprised three cases of
      asthma and one of rhinitis caused by chloramine-T (sodium- N-chlorine- p-toluene
      sulphonamide); as well as one case of asthma, seven cases of rhinitis, and two
      cases of combined rhinitis and conjunctivitis caused by natural rubber latex
      (NRL). Furthermore, one case of occupational rhinitis caused by Nobetec
      containing colophony was diagnosed. The incidence rate (IR) of ORD increased from
      0 in 1988 to a peak of 105.1 new cases per 100,000 working years in 1995. During
      the last observation year, i.e. 1998, the IR was 55 new cases per 100,000
      workers. The IR in dental personnel was lower than in the whole working
      population in Finland up until 1992, but since then has been greater than in the
      whole population, peaking in 1995 when the IR of dental personnel was 2.55 times
      greater than in the whole population. CONCLUSION: The present study shows the
      increasing frequency of respiratory hypersensitivity among dental personnel.
      Besides methacrylates, important causes of respiratory hypersensitivity are NRL
      and chloramine-T.

PMID- 11981654
TI  - Specific relationship between blood lead and air lead in the crystal industry.
AB  - OBJECTIVES: The main objective of the study was to establish the consequences of
      exposure to crystal dust on blood lead level in workers employed in hand
      finishing and grinding crystal pieces. The second objective was to research a
      relationship between ambient air lead and blood lead. METHODS: A study conducted
      in eastern France on 131 subjects occupationally exposed to an aerosol containing
      crystal particles involved personal measurements of atmospheric exposure to lead,
      determination of blood lead and, by questionnaire, collection of personal data on
      exposure characteristics, state of health and level of hygiene of survey
      volunteers. RESULTS: Initial analysis showed that differences in exposure at the
      workplace corresponded to differences in blood lead in the operators. There was
      definitely a potential risk of overexposure to lead, but the existence of this
      risk was not confirmed by level of blood lead concentrations and, moreover, no
      clinical signs of lead poisoning in the employees exposed were revealed. The
      existence of a relationship between personal air (PbA) and blood lead (PbB)
      levels in grinders and polishers was demonstrated. This relationship, of the form
      log PbB=2.064+0.181 x log PbA, turns out to be different from those provided by
      previously published models, which were developed from studies conducted in lead
      acid battery manufacturing plants and form the basis of national regulations.
      Thus, chronic exposure at 100 microg/m(3) of lead at a crystal-grinding workshop
      corresponds to a mean PbB level of 270 microg/l, whereas the recognized models
      estimate 350 to 500 microg/l. CONCLUSIONS: This study revealed a specific risk
      for these categories of exposed individuals. The origin of the descriptive model
      obtained for the lead exposure/ PbB level relationship raises, through the
      example of lead, the more general problem of the need to take into account
      differentiation of chemical substances containing the same element in biological
      monitoring.

PMID- 11981655
TI  - Computed tomography of asbestos-related pleural abnormalities.
AB  - OBJECTIVES: To study the observer agreement in several asbestos-related pleural
      abnormalities and to define criteria to discriminate between pleural changes in
      workers with occupational disease, and those in controls. METHODS: Pleural
      abnormalities in spiral computed tomography of 602 construction workers with
      asbestosis or bilateral pleural plaques and 49 controls were reviewed by three
      radiologists using structured forms. RESULTS: Intra- and inter-observer agreement
      (weighted kappa) was 0.4 or better with regard to the calcification, extent and
      thickness of pleural disease. These factors all correlated positively with the
      duration of asbestos exposure. There were significant differences in these
      pleural changes between the workers (mean extent per side 83 cm(2)) and controls
      (mean extent per side 40 cm(2)). Of the controls, 84% showed pleural lesions with
      an estimated extent of 10 cm(2) or more, bilateral in 64%. The extent of 45 cm(2)
      in pleural disease was the best value for discriminating between the controls and
      diseased workers, with a sensitivity of 82% and a specificity of 66%. The degree
      of pleural calcification, however, was the best discriminator between these
      groups, but quantitative methods are necessary for its use in the diagnostics of
      individuals. CONCLUSIONS: The extent, calcification and thickness were well
      repeatable indicators of benign pleural pathology and thus their use in future
      classification systems in computed tomography is recommended. In our material,
      the extent of 45 cm(2) and the degree of calcification were helpful in
      discriminating between pleural changes in workers with occupational disease, and
      those in controls who also presented marked pleural pathology.

PMID- 11981656
TI  - Different case definitions to describe the prevalence of occupational carpal
      tunnel syndrome in meat industry workers.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of carpal tunnel
      syndrome (CTS) in a group of meat industry workers, using typical symptoms,
      median nerve conduction studies (NCSs) and their combinations. In the case
      definition including the NCSs, we tested the electrodiagnostic reference values
      derived from the general healthy population and from the asymptomatic study
      population. METHODS: One-hundred fourteen workers were examined by clinical
      interviews and median NCSs. RESULTS: The prevalence of CTS varied from 11% to
      53%, with a progressive reduction passing from symptoms to NCSs to the their
      combinations. The prevalence was identical and the highest at the same time (53%)
      considering the case definitions based only on the symptoms and only on the NCSs
      with Kimura's reference values. Using the asymptomatic workers' electrodiagnostic
      reference values, alone or in combination with symptoms, the prevalence of CTS
      was the lowest (respectively, 15% and 11%). CONCLUSIONS: In the epidemiological
      studies, median NCSs should be considered desirable, if not essential, for
      confirming a clinical diagnosis, most of all in the longitudinal studies. In the
      future of CTS diagnosis, attention should be paid to the electrodiagnostic
      reference values that are discriminating to confirm the presence or not of the
      disease.

PMID- 11981657
TI  - Uranium mining in Germany: incidence of occupational diseases 1946-1999.
AB  - OBJECTIVES: In East Germany, uranium mining was performed on a large scale for
      approximately 45 years (1946-1990). In particular, the poor working conditions
      during the post-war years until 1955 led to a high level of occupational
      diseases. The present study gives an overview of the occurrence of occupational
      diseases during the mining period as well as after uranium mining was stopped in
      1990. METHODS: The number of occupational diseases which occurred during the
      mining period was calculated from the files of the former Wismut SDAG. Although
      exposure to uranium ceased after 1990, new cases of occupational diseases were
      recognized after that date. These were recorded by the German Federation Of
      Institutions For Statutory Accident Insurance And Prevention (HVBG). RESULTS AND
      CONCLUSIONS: Today, more than 35,000 cases of occupational diseases are known,
      and many more are expected. About two-thirds of them are lung diseases: 16,376
      cases of silicosis/silicotuberculosis and 7,695 cases of bronchial carcinomas.
      The increase in the number of recognized occupational diseases is shown and
      discussed against the background of changes in criteria for recognition and in
      working conditions as well as the duration of the latency period.

PMID- 11981658
TI  - Risk factors for neck-shoulder and wrist-hand symptoms in a 5-year follow-up
      study of 3,990 employees in Denmark.
AB  - OBJECTIVES: A prospective follow-up study of employees in Denmark was analyzed in
      order to investigate the association between physical and psychosocial exposures
      and musculoskeletal symptoms in the neck-shoulder and wrist-hand regions.
      METHODS: Data were derived from a 5-year follow-up questionnaire study of a
      sample of employees in Denmark, aged between 18 and 59 years. Occupational and
      individual background factors were assessed in 1990, and the associations with
      symptoms in 1995 were analyzed using logistic regression. The analysis was
      restricted to comprise employees free of symptoms in 1990. The neck-shoulder and
      wrist-hand analyses included 1,895 and 3,179 employees, respectively. RESULTS:
      Among men, neck-shoulder symptoms were predicted by twisting or bending (odds
      ratio (OR) 1.5, 95% confidence interval (CI) 1.01-2.26) and social support at
      work (OR 1.8, CI 1.24-2.50 for low versus rather high social support, OR 1.4, CI
      1.00-2.09 for high versus rather high social support). Furthermore, an
      interacting effect of heavy lifting and sedentary work was indicated. Symptoms in
      the wrist-hand region were predicted by stress symptoms (OR 1.7, CI 1.12-2.71)
      and twisting or bending (OR 1.7, CI 1.18-2.57). For women, smoking habits
      predicted neck-shoulder symptoms (OR 1.8, CI 1.14-2.82, former versus never
      smokers). Symptoms in the wrist-hand region were predicted by stress symptoms (OR
      1.7, CI 1.16-2.41) and twisting or bending (OR 1.9, CI 1.34-2.80). CONCLUSION:
      The results confirm that physical exposures at work influence the development of
      musculoskeletal symptoms in the neck-shoulder and wrist-hand regions. However,
      the results also suggest that a psychosocial exposure (social support) and
      perceived stress symptoms influence musculoskeletal symptoms.

PMID- 11981659
TI  - Gender differences in the effects from working conditions on mental health: a 4
      year follow-up.
AB  - OBJECTIVES: The overall aim was to examine how working conditions in 1993
      influenced the occurrence of poor mental health in 1997 among women and men from
      the general population. Also, the relative importance of other living conditions
      in relation to poor mental health in 1997 was examined. METHODS: A sample from
      the general Swedish population (originally examined in 1969) was followed up in
      1993 and 1997. Data from these follow-ups were analysed, and both bivariate and
      multivariate analyses of associations between occupational and non-occupational
      conditions in 1993 and poor mental health in 1997 -- defined as sub-clinical
      depression, reduced psychological well-being and high alcohol consumption -- were
      performed. RESULTS: Several occupational risk indicators were identified for poor
      mental health among women, especially sub-clinical depression and high alcohol
      consumption. Occupational factors such as shift work, job strain, no education at
      the employer's expense, low occupational pride, low stimulation at work and poor
      social support were related to poor mental health among women. For poor mental
      health among men, mainly sub-clinical depression, shift work and low occupational
      pride were identified as risk indicators. Non-occupational factors related to
      poor mental health among women were poor quality of social contacts, demanding
      life events, physical inactivity, high perceived physical load outside work and
      inadequate coping strategies. Among men, smoking and inadequate coping strategies
      were related to poor mental health. CONCLUSIONS: The difference between women and
      men, regarding the numbers of identified occupational and non-occupational risk
      indicators, may partly be explained by the gender-segregated labour market, and
      partly by other explanations. In our study, we have not succeeded in collecting
      the relevant information about occupational conditions that is important for
      men's mental health.

PMID- 11981660
TI  - The relationship between psychosocial work characteristics and fatigue and
      psychological distress.
AB  - OBJECTIVES: To examine the associations between psychosocial work characteristics
      and fatigue in employees in the Maastricht Cohort Study. A second objective was
      to compare the relationships for fatigue versus psychological distress with these
      psychosocial work characteristics. METHODS: The design was cross-sectional and
      included 11,020 employees who responded to the self-administered baseline
      questionnaire of the Maastricht Cohort Study. Fatigue was measured with the
      Checklist Individual Strength, a 20-item self-report instrument. Psychological
      distress was measured with the 12-item version of the General Health
      Questionnaire. Psychosocial work characteristics comprised: psychological
      demands, decision latitude, and social support at work as measured by the Job
      Content Questionnaire, as well as emotional demands at work, physical demands at
      work, job insecurity, and conflict with supervisor/co-worker, which were assessed
      with items from existing Dutch questionnaires. RESULTS: Low decision latitude and
      low social support at work were associated with fatigue in both men and women.
      Associations were also found between emotional demands at work, job insecurity,
      physical demands and conflict with supervisor and fatigue in men; and high
      psychological demands and fatigue in women. As regards psychological distress,
      there was no association with low decision latitude, but strong associations with
      emotional demands and conflict with supervisor in both genders. CONCLUSIONS: The
      study provides strong support for associations between psychosocial work
      characteristics and fatigue in men and women, even after adjustment for
      psychological distress. Moreover, it suggests some differential effects of
      psychosocial work characteristics on fatigue and psychological distress.

PMID- 11981661
TI  - Glove powder in the hospital environment -- consequences for healthcare workers.
AB  - OBJECTIVE: Exposure to starch powder from natural rubber latex medical gloves can
      cause allergy symptoms among healthcare employees and impair working conditions,
      due to the absorption of latex protein antigens onto the starch powder on the
      gloves. To evaluate and take care of this problem at Stockholm Soder Hospital we
      carried out this study. METHODS: A questionnaire was distributed to all employees
      working within the medical centre. The procedure was repeated after the centre
      had been changed to a powder-free working environment. The focus of the questions
      was to determine the extent of symptoms that could be associated with glove
      powder or latex proteins. RESULTS: Responses were compared before and 8 months
      after a new powder-free glove policy was fully implemented. The study pointed out
      that a relatively high percentage of the hospital workers were suffering from
      glove-related symptoms. A significant reduction of itching on the hands, hand
      eczema and upper respiratory-tract disorders was found after the change to a
      powder-free environment. CONCLUSION: It is not acceptable to use powdered medical
      gloves within health care. In spite of the risk of allergy and impairment of the
      working environment from powdered gloves, there is still only a minority of
      hospitals working according to a strict general powder-free policy. This study
      has pointed out that the reduced cost resulting from reduced absence through
      sickness further adds an argument for omitting glove powder and can justify the
      higher cost of using powder-free medical gloves.

PMID- 11981662
TI  - Carcinogen-specific mutation pattern in the p53 tumour suppressor gene in UV
      radiation-induced basal cell carcinoma.
AB  - OBJECTIVES: Basal cell carcinoma (BCC) is mainly caused by high and long-term UV
      radiation. UV radiation causes DNA damage in various genes. Mutations of the p53
      tumour suppressor gene have been identified in a wide variety of human cancers.
      The aim of the study was to analyse specific p53 mutations in BCCs in workers
      exposed to high and long-term UV radiation. METHODS: The mutation pattern of the
      p53 tumour suppressor gene was analysed in tissue from 12 patients with UV
      related BCC. All patients had a suspected occupational disease notified within
      the period 1995-1999. As a control, 20 BCC skin samples removed from areas
      definitively unexposed to sunlight were analysed. The specific mutations were
      determined by direct sequencing of codon 4 to 9 of the p53 gene in carcinomatous
      and adjacent non-neoplastic tissue after microdissection. Immunohistochemical
      analysis was performed to detect p53 protein. RESULTS: p53 mutations were
      detected in 7/12 cases (58%). Point mutations were found in six cases (50%). In
      one case a deletion of 24 base pairs was observed. The most frequent mutations we
      found were CC-->TT base-pair changes in four and C-->T mutations in two cases.
      Within the control group specific p53 mutations were found in 11 cases (55%)
      without any C-->T predominance. No case showed CC-->TT mutations. CONCLUSIONS:
      Mutations of the p53 tumour suppressor gene in UV-associated BCC are frequent
      events. A predominance of C-->T mutations and tandem CC-->TT base-pair changes
      were observed in the sunlight-exposed cases only supporting the idea of site
      directed mutagenesis by UV radiation in human BCC.

PMID- 11981665
TI  - Chemosensory irritation and the setting of occupational exposure limits.

PMID- 11981666
TI  - Odor, irritation and perception of health risk.
AB  - OBJECTIVES: Understanding the potential for volatile chemicals to elicit
      chemosensory irritation in the upper respiratory tract is critical to setting
      occupational exposure limits that are protective of comfort and well-being for
      the majority of workers. However, the determination of irritant potency for any
      volatile chemical has been limited by the lack of reliable and non-invasive
      assays for studying sensory irritation in humans and a failure to appreciate the
      many non-sensory factors that can influence the reactions to an odor or an
      irritant in the workplace. METHODS: This paper reviews the issues involved in
      distinguishing and measuring sensations of odor and irritation from volatile
      chemicals, and describes recent developments in psychophysical methods for
      evaluating chemical irritancy in humans, and discusses some of the many non
      sensory factors such as exposure history, attitudes and expectations and
      personality variables that can significantly alter the perception of odor,
      irritation and health risk following exposure to a volatile chemical. RESULTS:
      The availability of safe, non-invasive assays to measure directly odor and
      irritant responses in the species of interest, humans, can both simplify and
      improve accuracy in the process of developing appropriate occupational exposure
      guidelines. CONCLUSIONS: Objective measures of irritation onset obtained in
      conjunction with subjective responses can lend valuable input to the decision
      process for determining occupational exposure limits but should always account
      for other factors (e.g., cognitive or emotional) that may be modulating the
      subjective response.

PMID- 11981667
TI  - Assessment of rhinological parameters for evaluating the effects of airborne
      irritants to the nasal epithelium.
AB  - OBJECTIVES: The initial contact area of inhaled toxins with the human body is the
      nasal mucosa. Upon irritation, nasal symptoms may occur that are well known as
      common viral infections of the airway and thus neglected by patients and
      physicians. Therefore, objective methods should be used to determine even minor
      irritative or inflammatory changes. METHODS: Objective methods to assess changes
      in the nasal epithelium include endoscopy, rhinomanometry, acoustic rhinometry,
      anemometry, thermometry, laser Doppler flowmetry, measurements of mucociliary
      transport time and ciliary beat frequency, analysis of nasal secretions, nasal
      cytology, and subjective (UPSIT, CCCRC, Sniffin Sticks) and objective (electro
      olfactogram, olfactory event related potentials) and olfaction tests. RESULTS:
      Several different inhaled irritative and toxic substances, including metal dusts
      and steam, volatile organic substances, and inorganic gases, may harm the nasal
      epithelium. CONCLUSIONS: The objective evaluation of nasal functions should be
      used to assess effects of airborne irritants. For patients complaining of toxic
      effects, early diagnosis is important in the prevention of severe damage to the
      upper and lower airways.

PMID- 11981668
TI  - Biomarkers and chemosensory irritations.
AB  - OBJECTIVES: A literature review on studies in humans, applying physiological
      methods to monitor environmentally induced reactions in eyes and upper
      respiratory tract. The focus was on chemical exposures, but other occupational
      factors and indoor exposures were included. METHODS: Original articles were
      gathered from Medline until November 2000, combined with peer-reviewed
      publications from other sources. RESULTS: Ocular methods included measurement of
      tear film break-up time (BUT), blink frequency, detection of corneal damage, by
      vital staining, and cells or inflammatory markers in tear fluid. Nasal methods
      included acoustic rhinometry, rhinostereometry, and nasal peak expiratory flow.
      In addition, nasal lavage with isotonic sodium chloride solution was applied to
      measure concentrations of leucocytes, or biomarkers of secretion or inflammation
      in nasal lavage fluid (NAL). Most occupational studies were on nasal effects of
      organic or inorganic dust. There were few studies on occupational exposure to
      organic solvents or chemical irritants. Some studies demonstrated associations
      between ocular and nasal physiological response and the indoor environment.
      Finally, there were some exposure-chamber studies on effects of specific volatile
      organic compounds (VOCs). Little is known about adaptation at repeated ocular or
      nasal exposure to irritants. CONCLUSION: Physiological measurements can be
      valuable complements to symptom registration, but there is a need for
      standardised investigations. There is a lack of studies on ocular and nasal
      physiological responses in relation to specific chemical compounds. Experimental
      studies, with repeated exposure and longer follow-up time on biomarkers, are
      needed. Finally, there is a need for longitudinal epidemiological studies to
      elucidate if observed effects should be interpreted as variation within normal
      physiology, or as early signs of impaired ocular and respiratory health.

PMID- 11981669
TI  - Intranasal chemosensory function of the trigeminal nerve and aspects of its
      relation to olfaction.
AB  - OBJECTIVES: The review outlines characteristics of the intranasal trigeminal
      chemosensory system. In addition, it provides selective comparisons of the
      trigeminal and olfactory systems, the two of which interact at multiple levels.
      RESULTS AND CONCLUSIONS: This interaction between the trigeminal and olfactory
      systems is an important determinant of sensations of odor. Further, it appears to
      change as a result of aging and disease. Thus, the interaction between the
      olfactory and trigeminal systems is not straightforward and may be difficult to
      predict, but it has a powerful influence on the perception of odors.

PMID- 11981670
TI  - Psychological reactions related to chemosensory irritation.
AB  - OBJECTIVES: For risk assessments of solvents the knowledge on chemosensory
      irritation effects is important, but the methodological base for that is
      incomplete. The psychological approach measuring chemosensory irritations leans
      on perceived symptoms and self-reported changes of well being. Characteristics
      assessing the validity of such psychological approaches are presented. METHODS:
      The article is based on 14 experimental inhalation studies with (mostly) 4-h
      exposures to acetone, 2-butanone, ethanol, ethyl acetate, ethyl benzene, iso
      propanol, 1-octanol, and styrene. The profiles of exposure include constant and
      changing concentrations using the range of the German maximum concentrations at
      the workplace (MAK) list. Irritations (eyes and nose), olfactory symptoms
      (odour), and annoyance are the dependent variables measured by ratings. Young and
      healthy subjects ( n=160), - partially, subjects with self-reported odour
      sensitivity (measured by items from the questionnaire on chemical and general
      environmental sensitivity) - were investigated. RESULTS: The reliability of
      ratings is sufficient. Dose-response relationships for perceived odour and
      annoyance are stronger than those for irritations. A ranked order of the size of
      effect (related to the values before exposure) for the substances investigated
      shows correspondence between odour and annoyance; that for irritation differs.
      Within the limits of the MAK list, perceived irritations are not correlated to
      annoyance, whereas perceived bad smell correlates significantly to annoyance.
      Reversibility of the self-reported effects to approximately the pre-exposure
      level can be shown 1 h after cessation of the experimental exposure for the
      "normal" subjects. Influences of trait anxiety and chemical sensitivity on
      reports of annoyance, bad odour or irritation are only weak. CONCLUSION: The
      psychological approach of repeated measurements for self-reported irritation
      includes distinctive advantages compared with other methods, the simple and
      repeated availability during exposure, the sufficient reliability and dose
      response relationship, and the comparability between substances by means of
      effect size. The extension of the concept of "chemosensory irritations" on
      reports for annoyance and bad smell can be recommended.

PMID- 11981671
TI  - Chemosensory irritation and the lung.
AB  - Airway irritation involves a variety of reflex mechanisms. Tracheal and bronchial
      C fibres and rapidly adapting fibres mediate cough, bronchoconstriction, and
      mucosal vasodilation. Workplace respiratory irritants can have a variety of
      effects in relation to asthma. Very high exposures can cause new-onset asthma,
      clinically presenting as reactive airways dysfunction syndrome or irritant
      induced asthma. Symptoms after exposure to irritants depend on aggregate
      characteristics, water solubility and dose. Measurement of pulmonary function in
      response to irritants includes baseline spirometry, monitoring of across-shift
      changes and changes in non-specific bronchial responsiveness as well as bronchial
      responsiveness to inhaled allergens. Following irritant exposure, inflammatory
      changes within the airways are monitored by bronchoalveolar lavage or - less
      invasively - by sputum markers. A completely non-invasive approach not limited in
      repeatability is the investigation of inflammatory markers in exhaled air.
      However, the diagnostic and prognostic values of these novel markers have still
      to be demonstrated.

PMID- 11981672
TI  - Vibrotactile sense and mechanical functional state of the arm and hand among
      computer users compared with a control group.
AB  - OBJECTIVES: To measure sensory perception and mechanical muscle function of the
      arm among experienced female computer users with (+sPC) and without (-sPC)
      symptoms compared with a control group (ctrl). METHODS: Group +sPC had severe
      symptoms in the hand/wrist and/or the forearm/elbow region. They worked with the
      computer 75% and used a computer mouse 50% of the working day. Group -sPC had no
      or minimal symptoms. They used the computer 80% and a computer mouse 58% of the
      working day. The control group had no symptoms and worked with the computer for 2
      h or fewer per day. Sensory perception threshold was measured using
      vibrotactilometry at five sites on the right hand representing nn. medianus,
      ulnaris and radialis. Mechanical muscle function was assessed by measuring muscle
      strength, wrist extension endurance, hand-eye co-ordination, and range of motion.
      Furthermore, performance was measured during standardized computer work. RESULTS:
      The perception thresholds for +sPC were greater in the areas innervated by n.
      medianus and n. ulnaris than for non-symptomatic groups, indicating that nerve
      compression is involved. For n. radialis, no differences were found between
      groups. No difference in isometric muscle strength was found for hand-grip, wrist
      extension, vertical pinch-grip and knee extension. However, for horizontal pinch
      grip (pronated forearm) lower values were obtained for the +sPC group than for
      non-symptomatic groups. At the end of the endurance task, the perceived exertion
      was highest for +sPC. Furthermore, slower recovery was found for +sPC. No
      differences in range of motion, hand-eye co-ordination, and error rate during
      computer work were found between groups. CONCLUSIONS: Increased perception
      threshold values indicating entrapment of n. medianus and n. ulnaris were found
      for +sPC. Only few differences in mechanical muscle performance were found among
      the groups. The +sPC group had lower pinch-grip strength when measured in the
      pronated hand position, and the results indicated shorter muscle endurance for
      +sPC than for -sPC and ctrl.

PMID- 11981673
TI  - Urinary benzylmercapturic acid as a marker of occupational exposure to toluene.
AB  - OBJECTIVE: To examine if benzylmercapturic acid (or N-acetyl- S-benzyl cysteine)
      in urine can be used as a marker of occupational exposure to toluene. METHODS: A
      factory survey was conducted in the latter half of a working week. A group of 46
      men, who volunteered for the study, was engaged in ink preparation, surface
      coating or printing work. Diffusive samplers were used to measure average solvent
      exposure in an 8-h shift. End-of-shift urine samples were analyzed for
      benzylmercapturic acid (BMA) by a modification of an HPLC method originally
      developed for phenylmercapturic acid determination. RESULTS: The workers were
      exposed primarily to toluene [TOL; 13 ppm as the geometric mean (GM) and 86 ppm
      at the maximum] together with isopropyl alcohol (<1 and 4 ppm), ethyl acetate (2
      and 127 ppm) and methyl ethyl ketone (2 and 142 ppm). BMA in urine correlated
      closely [correlation coefficient ( r) =0.7] with TOL in air, irrespective of
      correction for urine density. The lowest TOL concentration at which urinary BMA
      increased to a measurable level was approximately 10 ppm, and urinary BMA could
      separate the exposed from the non-exposed when TOL exposure was 15 ppm or higher.
      CONCLUSIONS: BMA in end-of-shift urine samples is a good marker of occupational
      TOL exposure. Urinalysis for BMA is sensitive enough to detect TOL exposure at 15
      ppm, and therefore BMA appears to be more sensitive than hippuric acid and
      possibly o-cresol as a urinary marker of TOL exposure.

PMID- 11981674
TI  - Association between exhaled nitric oxide, ambient air pollution and respiratory
      health in school children.
AB  - OBJECTIVES: The aim of the study was to investigate whether the level of exhaled
      nitric oxide (eNO) provides a more sensitive measure to assess adverse pulmonary
      effects of air pollution than conventional lung function indices. METHOD: The non
      selected cohort studied consisted of 68 children (aged 10-11 years) living in an
      urban environment. For 7 weeks respiratory complaints were reported daily by
      these children in a diary, and lung function measures and eNO levels were
      determined in the children once a week on days with various level of air
      pollution. RESULTS: During the study the increase in the levels of the various
      air pollutants was positively associated with eNO (6% to 31% increase; P<0.05)
      but not with lung function measures. In contrast to the lung function measures,
      the prevalence of respiratory symptoms such as "sore throat", "runny nose",
      "having a cold", and "sick at home" were positively associated with the level of
      eNO measured in the following week. CONCLUSIONS: Though clinically very
      meaningful, functional pulmonary measures appear to be too course to detect
      relatively mild clinical symptoms in response to exposure to air pollution. In an
      epidemiological setting the increase in eNO may represent a more suitable measure
      to assess such adverse effects.

PMID- 11981675
TI  - Ambient and biological monitoring of coke plant workers -- determination of
      exposure to polycyclic aromatic hydrocarbons.
AB  - OBJECTIVES: The aims of this study were to determine external and internal
      polycyclic aromatic hydrocarbon (PAH) exposure in a coke plant and to contribute
      to the evaluation of biological limit values. METHODS: Personal air sampling was
      carried out on a study population of 24 coke plant workers. In detail, 16 PAHs
      were determined, among them phenanthrene, pyrene and benzo[ a]pyrene. For the
      determination of internal exposure, post-shift urine samples from the workers
      were examined for hydroxylated metabolites of pyrene (1-hydroxypyrene, 1-OHP) and
      phenanthrene (1-, 2+9-, 3-, 4-hydroxyphenanthrene, 1-, 2+9-, 3-, 4-OHPhe). In
      both cases, approved HPLC methods were used. RESULTS: The workers were classified
      into three groups. The group most exposed was that on the top side of the coke
      oven, with a mean value of 491.2 microg/m(3) for the sum of all sixteen PAHs. The
      mean value at the bench side was 26.61 microg/m(3), while it was 76.18
      microg/m(3) in the group of workers with no dedicated location (=complete area).
      Both the excretion of 1-OHP and the sum of hydroxyphenanthrenes had the highest
      mean levels in the top side group of workers (mean: 19.70 microg/g creatinine
      (crea.) and 39.18 microg/g crea.), followed by the bench-side workers (mean: 7.01
      microg/g crea. and 12.95 microg/g crea.) and the whole-area workers (mean: 3.57
      microg/g crea. and 8.70 micorg/g crea.). The concentrations of all urinary
      metabolites correlated significantly with benzo[ a]pyrene (BaP) in the air.
      CONCLUSIONS: According to these correlations, urinary concentrations of 8 and 11
      microg 1-OHP/g crea., respectively 16 and 23 microg/g crea. for the sum of
      hydroxyphenanthrenes, correspond to BaP concentrations in air of 2 and 5
      micorg/m(3), the German technical guiding concentration (TRK value). Our results
      are in line with others reported in the literature. That means that it should be
      possible today to define a standard of occupational hygiene and medicine in coke
      plants using the elimination of hydroxyphenanthrenes and hydroxypyrene in urine
      as markers for internal PAH exposure.

PMID- 11981676
TI  - Irritation of the human eye mucous membrane caused by airborne pollutants.
AB  - OBJECTIVES: The purpose of this study was to investigate the different irritative
      effects of carbon dioxide and n-butanol exposure on the ocular mucous membrane.
      MATERIAL AND METHODS: Provocation by the gases was at the same sensory level,
      which was 50% of maximum on a linear scale. The experiment was performed on nine
      healthy subjects with the aim of identifying the relationship between eye
      irritation and the human physiological response to this irritation. A goggle
      exposure system, invented at the Department of Occupational and Environmental
      Medicine, Aarhus University, was used for the experiment. The exposures lasted
      for 30 min each. RESULTS: There were no changes in tear film stability and
      conjunctival corrosion (lissamine staining) after carbon dioxide and n-butanol
      exposures leading to 50% sensory eye irritation. However, the study showed a
      delayed inflammatory response after carbon dioxide exposure when compared with
      clean air. The significant change was seen for tear fluid neutrophilic
      granulocytes 22 h after carbon dioxide (CO(2)) exposure only. CONCLUSIONS: It is
      concluded that the type of exposure made no difference to the elicited
      physiological responses and that tear film stability and epithelium damage were
      not affected by sensory irritation itself.

PMID- 11981677
TI  - Surgical management of intra-abdominal infection: is there any evidence?
AB  - The aim of this review article was to look at the evidence supporting the
      surgical treatment of secondary bacterial peritonitis. Because the absolute
      necessity of adequate source control is not disputable and there is no question
      that peritoneal toilet (in whichever form) is mandatory, the main bulk of this
      manuscript is dedicated to the controversial issues of planned relaparotomy and
      laparostomy. We found little good evidence to support or refute the use of these
      modalities, but in the absence of evidence, one has to use experience and common
      sense. Ours suggest that planned relaparotomies combined with laparostomy
      represent, for the time being, the heaviest weaponry in the surgeon's mechanical
      armamentarium for the treatment of severe intra-abdominal infection. Even without
      level II evidence, we are convinced that these therapeutic modalities are life
      saving in a well-selected group of patients. One has, however, to know when to
      stop and how not to harm.

PMID- 11981678
TI  - Trevira mesh: a promising new implant for the treatment of abdominal hernias.
AB  - BACKGROUND: Trevira (polyethylene terephthalate) has been in clinical use for
      more than 20 years, serving as implant material with minimal foreign body
      reaction for the replacement of the cruciate ligaments of the knee. An animal
      (pig) trial was performed to ascertain whether a Trevira mesh offers any
      advantages over currently employed meshes like Prolene for abdominal hernia
      repair. METHODS: In 12 mini-pigs 10 x 10 cm of the musculofascial abdominal layer
      was resected preserving the peritoneum. Subsequently, a 15 x 15 cm synthetic mesh
      was implanted (Prolene, Ethicon, Norderstedt, Germany, or Trevira, Telos GmbH,
      Marburg, Germany, in six animals each) using sublay technique. The main focus was
      on the extent of the chronic foreign body reaction. This was assessed by a
      pathologist who paid special attention to the presence of foreign body giant
      cells after 2 and 6 months. A further assessment was made of shrinkage of the
      implant as a result of foreign body reaction. RESULTS: The number of giant cells
      after two months was significantly higher with the Prolene implant than with the
      Trevira implant (Prolene 2.2+/-0.4, Trevira 0.8+/-0.2, per fixed microscopic
      field; P<0.05). After 6 months the number of giant cells associated with the
      Prolene implants rose further, while it remained relatively constant for those of
      Trevira (Prolene 4.6+/-1.3, Trevira 1.1+/-0.5; P<0.05). No significant difference
      was noted over time between the two types of implant with regard to shrinkage (2
      months: Prolene 0.8+/-0.3 cm(2), Trevira 0.6+/-0.4 cm(2); 6 months: Prolene 1.3+/
      0.6 cm(2), Trevira 1.1+/-0.5 cm(2)). CONCLUSION: In this animal study Trevira
      mesh demonstrated a high biocompatibility with a low foreign body reaction; it
      appears to be a promising new implant for the treatment of hernias.

PMID- 11981679
TI  - Revision of the multiple organ failure score.
AB  - BACKGROUND AND AIM: The multiple organ failure (MOF) score published by Goris et
      al. in 1985 was one of the first attempts to quantify severity of organ
      dysfunction and failure based on expert opinion in surgical intensive care unit
      patients. Fifteen years later a reassessment of this score is mandatory. PATIENTS
      AND METHODS: Daily MOF scores were documented in patients admitted to the
      surgical ICUs in Nijmegen (NL) and Cologne (D). Patients with an ICU stay < or =
      3 days were excluded. Organ dysfunction (1 point) and organ failure (2 points)
      were recorded for the following organ systems: lung, heart, kidney, liver, blood,
      gastrointestinal tract (GI), and central nervous system (CNS). Maximum scores
      were computed, and logistic regression analysis was used to optimize point
      weights for each organ system. Predictive power was analyzed using receiver
      operating characteristic (ROC) curves. RESULTS: In all, 147 patients, mean age 56
      years, were included with a total of 2,354 observation days. Hospital mortality
      was 30.6%. GI failure was present on only 3.3% of days, without impact on
      mortality. Valid evaluation of CNS was impossible in most cases due to sedation
      and ventilation. Reweighting of the score items revealed only marginal
      improvements in prediction. Mortality consistently increased with increase in
      number of failed organs. This phenomenon was even more pronounced in older
      patients, e.g., 55% mortality (age > or = 60) versus 0% (age < 60) with two
      failing organs. CONCLUSION: Due to problems in definition and assessment
      (reliability) CNS and GI should not be considered in future assessments of the
      MOF score. The original point weights in the remaining five organ systems provide
      a valid and reliable risk stratification, at least in surgical ICU patients.

PMID- 11981680
TI  - Prophylactic nasal continuous positive airway pressure after major vascular
      surgery: results of a prospective randomized trial.
AB  - BACKGROUND: The efficacy of nasal continuous positive airway pressure (nCPAP) as
      a prophylactic method for preventing cardiopulmonary complications after major
      vascular surgery has not been investigated. PATIENTS/METHODS: In a prospective
      randomized trial, 204 patients undergoing elective midline laparotomy for
      vascular surgery were randomized to receive standard therapy ( n=105) or
      additional prophylactic nCPAP ( n=99) for the first postoperative night.
      Postoperative oxygenation, incidence of severe cardiac, and pulmonary
      complications, length of intensive care surveillance and length of total
      postoperative hospital stay (LOS) were compared. RESULTS: Prophylactic nCPAP
      significantly reduced the number of patients with severe oxygenation disturbances
      defined as paO(2) < 70 mmHg with FiO(2) > or = 0.7 (5 versus 17, P=.01). There
      were no differences with respect to death, cardiac and pulmonary complications,
      length of intensive care surveillance or LOS. CONCLUSION: Prophylactic 12 h nCPAP
      significantly reduces the occurrence of postoperative oxygenation disturbances
      but has no effect on cardiac or pulmonary complications, need for intensive care,
      LOS or mortality after major vascular surgery.

PMID- 11981681
TI  - Pyogenic liver abscess -- 20 years' experience. Comparison of results of
      treatment in two periods.
AB  - BACKGROUND AND AIMS: Our aim is to give an audit of our experience over the past
      two decades in the form of a retrospective study. PATIENTS/METHODS: In two equal
      periods between 01.01.1982 and 31.03.2001, 56 patients (37 males and 19 females)
      with pyogenic liver abscess were treated. Image-guided percutaneous drainage was
      performed in 22.2%/20.6% of the patients; the remainder were treated with open
      drainage with or without biliary tract reconstruction and liver resection. For
      antibiotic perfusion of the liver an umbilical vein cannula was inserted in
      40.7%/24.1%. Microbiological findings, types of therapy, complications and
      mortality, etiology, patient characteristics, symptoms, and laboratory data were
      investigated. The results in the two groups were compared and analyzed
      statistically. RESULTS: The most common cause of abscess, biliary disease, was
      seen more often in the second period. Solitary liver abscesses were more
      frequent. The only characteristic biochemical finding was an elevated alkaline
      phosphatase level. There were more positive cultures in the second period
      (70.4%/79.3%), and the number of Escherichia coli or Enterobacter aerogenes
      infections also increased. In the first period the mortality was 18.5%, whereas
      in the second no patients were lost. CONCLUSION: We suggest the importance of
      individualized therapy based on an early and exact diagnosis. The first treatment
      step should be image-guided drainage, but under well-defined circumstances open
      drainage can also be performed with good results.

PMID- 11981682
TI  - Thoracoscopy versus thoracotomy: a prospective comparison of trauma and quality
      of life.
AB  - BACKGROUND: Reliable comparisons of thoracoscopy (TCC) and anterolateral
      thoracotomy (ATT) with regard to trauma and post-operative quality of life are
      rare. This study was conducted to quantify the results of TCC, which was expected
      to show an advantage. METHODS: Using a matched-pair design (matching criteria:
      comparable intracavitary procedure, benign/malignant disease and sex), 22
      patients were compared who underwent either TCC or ATT (Wilcoxon matched-pairs
      signed-ranks test, P<0.05). RESULTS: Incision and operation time were shorter for
      TCC (TCC 5.3 vs ATT 23.7 cm, P=0.003; TCC 64 vs ATT 87 min, P=0.029). Differences
      in favor of TCC were detected for interleukin 6 (IL6) (TCC 17.2 vs ATT 105.6
      pg/ml, P=0.036) in the immediate postoperative period, C-reactive protein (CRP)
      (TCC 28.2 vs ATT 86.6 mg/l; P=0.010) on the day 1 after the operation, forced
      vital capacity (FVC) (TCC 2.5 vs ATT 1.5 l, P=0.0173), elevation of the arm (EA)
      (TCC 143 vs ATT 109; P=0,026), pain on coughing (CP) (TCC 2.5 vs ATT 6.9
      patients; P=0.009) and Spitzer Index (SI) (TCC 9.2 vs ATT 7,1 patients; P=0.009),
      as well as CP (TCC 1.4 vs ATT 4.4 patients; P=0,005) on day 4 after the
      operation. Forced expiratory volume in the first second, pain, creatin kinase,
      blood glucose and neopterin showed no differences. CONCLUSIONS: In terms of
      surgical trauma and quality of life ICC is superior to ATT in the immediate
      postoperative period. With the exception of pain and coughing, there were no
      differences after postoperative day 4.

PMID- 11981683
TI  - Biliary reconstruction following right adult living donor liver transplantation
      end-to-end or end-to-side duct-to-duct anastomosis.
AB  - BACKGROUND AND AIMS: Bile duct complications are the modern Achilles' heel of
      adult-to-adult living donor liver transplantation. A duct-to-duct anastomosis is
      currently performed in the presence of single graft ducts, while
      cholangiojejunostomy is used to drain multiple ducts. Our aim is to describe the
      feasibility of duct-to-duct anastomoses independent of the presence of one or
      multiple graft bile ducts. METHODS: The probe technique for right bile duct
      dissection in donors and a proximal hilar bile duct division in recipients are
      illustrated. The BARIGA LDLT (biliary anastomosis in right graft for adult living
      donor liver transplantation recipients) with end-to-side or end-to-end hepatico
      hepaticostomy was used in five recipients of right grafts (segments 5-8).
      RESULTS: All donors and recipients are doing well; all grafts are functional at
      13 months. Duct-to-duct anastomoses to single, double, or triple graft ducts have
      been performed. Two early anastomotic stenoses at 5 and 10 weeks were
      successfully treated endoscopically. CONCLUSION: The duct-to-duct anastomosis
      represents a valid alternative to the standard hepaticojejunostomy for right
      living donor liver grafts. Using this method, biliary complications can be
      treated endoscopically. End-to-side or end-to-end BARIGA LDLT has the potential
      to become a standard method in segmental transplantation, including split liver.

PMID- 11981684
TI  - Laparoscopic common bile duct exploration.
AB  - In recent years, laparoscopic common bile duct exploration has become the
      procedure of choice in the management of choledocholithiasis in several
      laparoscopic centers. The increasing interest for this laparoscopic approach is
      due to the development of instrumentation and technique, allowing the procedure
      to be performed safely, and it is also the result of the revised role of
      endoscopic retrograde cholangiopancreatography, which has been questioned because
      of its cost, risk of complications and effectiveness. Many surgeons, however, are
      still not familiar with this technique. In this article we discuss the technique
      and results of laparoscopic common bile duct exploration. Both the laparoscopic
      transcystic approach and choledochotomy are discussed, together with the results
      given in the literature. When one considers the costs, morbidity, mortality and
      the time required before the patient can return to work, it would appear that
      laparoscopic cholecystectomy with common bile duct exploration is more favorable
      than open surgery or laparoscopic cholecystectomy with preoperative or
      postoperative endoscopic sphincterotomy. However, the technique requires advanced
      laparoscopic skills, including suturing, knot tying, the use of a
      choledochoscope, guidewire, dilators and balloon stone extractor. Although
      laparoscopic common bile duct exploration appears to be the most cost-effective
      method to treat common bile duct stones, it should be emphasized that this
      procedure is very challenging, and it should be performed by well-trained
      laparoscopic surgeons with experience in biliary surgery.

PMID- 11981685
TI  - Severity scores in surgery: what for and who needs them? An introduction:
      definition, aims, classification and evaluation.
AB  - Every patient represents a unique and complex situation a clinician has to deal
      with. In order to cope with this complexity of information, reduction is
      necessary, especially in communication about diseases or therapy. The first
      reduction is made when a patient is given a diagnosis which reflects a
      constellation of similar symptoms. A score also reduces the given amount of
      clinical data into a one-dimensional value. The primary aim of a score is a
      systematic comparison between patients and institutions. Scores reduce
      information to focus on the essentials. They are used for severity classification
      and prognosis, evaluation of outcome and treatment effects, case-mix adjustments
      in comparative audits, and economic evaluation. Quality criteria of score systems
      which should be considered in the development and application are: reliability,
      validity, measurability, applicability, and clinical relevance. This introductory
      article gives a brief description of these terms.

PMID- 11981686
TI  - Severity scores in surgery: what for and who needs them?
AB  - Scoring systems which try to quantify patient risk are becoming increasingly
      popular. They have been widely used in intensive care unit patients, trauma
      patients, and patients undergoing operation. Both general scores, such as APACHE
      and POSSUM, and specific scores, such as the Detsky Index for post-operative
      cardiac morbidity and mortality, have been defined. They can be used for
      comparative audit, to define treatment options, to predict long- and short-term
      outcome, and to define morbidity and mortality associated with a specific
      condition. Little evidence yet exists that it is possible to move patients from
      higher to lower risk groups and thus lower post-operative mortality. However,
      this may be achieved in time. All surgeons need to be involved in further
      refinements of scoring systems.

PMID- 11981687
TI  - Extraparenchymal renal artery aneurysms: is hypertension an indication for
      revascularization surgery?
AB  - We report here the surgical management of extraparenchymal renal artery aneurysms
      associated with hypertension and the results of this treatment. From January 1978
      through December 1999, 19 consecutive patients with 23 extraparenchymal renal
      artery aneurysms underwent surgery with renal revascularization techniques. Of
      these 19 patients, 89.5% had systemic hypertension, and 12 of 16 patients had
      associated renovascular hypertension. Twenty of the aneurysms were patent, one
      was chronically thrombosed, and one patient presented with acute thrombosis of
      abdominal aortic and bilateral renal aneurysms; 11 of the 20 patent cases had
      significant stenosis in the preoperative arteriography. Seventeen aneurysms (74%)
      were located on the main trunk of the renal artery. Response of hypertension and
      renal function were examined. Surgical technique patency was evaluated by life
      table methods. Our basic surgical indication for extraparenchymal renal artery
      aneurysms in this series was renovascular hypertension. Nonrenal hypertension
      alone does not indicate surgery. We consider the saphenous vein to be the graft
      of choice for renal revascularization.

PMID- 11981688
TI  - Outcome after simultaneous abdominal aortic aneurysm repair and aortocoronary
      bypass.
AB  - Myocardial infarction remains the leading cause of early and late death after
      abdominal aortic aneurysm (AAA) repair. Myocardial revascularization is staged
      either before or concomitant with AAA resection, but results are far from
      uniform. We retrospectively analyzed our experience with patients who underwent
      concomitant AAA resection and aortocoronary bypass (ACB) to examine the factors
      affecting early morbidity/mortality and early results. Forty-two patients (all
      men; mean age, 67.2 years) underwent simultaneous ACB grafting and AAA repair
      between 1975 and 1998. All were managed postoperatively in the cardiothoracic
      intensive care unit (mean stay, 6.1 days). The mean total hospital stay was 17.2
      days. Two died in the early postoperative period (4.8%): 1 of sustained
      myocardial failure following a third ACB, and 1 of coagulopathy after concomitant
      ACB, aortic valve replacement, and AAA. One patient developed a nonfatal MI on
      postoperative day 3. The incidence of wound and bleeding complications was higher
      for patients undergoing both ACB and AAA repair than for patients undergoing AAA
      resection alone. On follow-up (mean, 10 years; range, 7 months to 15 years), only
      2 of 10 late deaths were due to cardiovascular causes. We believe that
      concomitant myocardial revascularization is warranted in select patients
      requiring elective or urgent AAA resection in order to decrease perioperative
      risk and improve late survival. Cardiac failure or ischemia during aortic surgery
      can be prevented by proper perfusion with or without cardiopulmonary bypass. In
      patients undergoing simultaneous procedures, the increased risk is related to the
      severity of the vascular and coronary artery disease and not to the combined
      operations.

PMID- 11981689
TI  - Appropriate indications for venous duplex scanning based on D-dimer assay.
AB  - Because of the rapid growth in requests for lower extremity duplex scanning, we
      tested a new rapid D-dimer assay method, the Miniquant test, for its ability to
      rule out deep vein thrombosis (DVT) in patient subgroups with the following risk
      factors: malignancy, postoperative state, and cellulitis. One hundred twenty-six
      consecutive patients with suspected DVT underwent clinical assessment, D-dimer
      testing with quantitative Miniquant D-dimer assay, and duplex scanning according
      to standard criteria for the diagnosis of DVT. Sensitivity, specificity, negative
      predictive value (NPV), and positive predictive value (PPV) were calculated
      versus duplex scanning for the various risk factor subgroups. Our results showed
      that the Miniquant D-dimer assay is useful preselection procedure (high NPV) in
      selected patient subgroups with suspected proximal DVT, including patients with
      cellulitis and those without malignancy or postoperative state. This preselection
      procedure has the potential for avoiding a large proportion of unnecessary duplex
      scanning, thus saving time and reducing costs.

PMID- 11981703
TI  - Biventricular pacing in patients with ICD: how many patients are possible
      candidates?
AB  - BACKGROUND: About 80 % of patients receiving an implantable cardioverter
      defibrillator (ICD) due to life-threatening episodes of ventricular tachycardia
      (VT) or ventricular fibrillation (VF) have structural heart disease. ICD
      implantation reduces the risk of sudden cardiac death to less than 2 %. However,
      the major obstacle in these patients is chronic heart failure (CHF).
      Biventricular stimulation (BIV) has shown its efficiency as an alternative
      therapy in drug refractory CHF. METHODS: According to the InSync registry, we
      predefined possible indications for BIV as follows: complete branch bundle block
      (> 120 ms), left-ventricular ejection fraction (EF) < 35 % and NYHA class > II.
      We evaluated the number of patients presenting this indication at time of implant
      and during follow-up (FU) at our ICD clinic. RESULTS: Between 1992 and 1998, 360
      patients were provided with an ICD (mean age 64.6 +/- 5.4 yrs, mean EF 37 +/- 14
      % at implant, 82 % of patients with organic heart disease). Mean FU was 34 +/- 21
      months. During FU 46 patients (13 %) died, 15 of these (33 %) presenting criteria
      for BIV. 33 patients died of heart failure, there was 1 sudden death and 12
      patients died for non-cardiac reasons. 35 % of the patients who died of heart
      failure had an indication for BIV. CONCLUSIONS: About 10 % of ICD patients had an
      indication for BIV at time of implant. Over a mean FU period of 34 months, 16% of
      all patients presented an indication for BIV. Patients with an indication for BIV
      had a higher mortality rate and more frequent atrial fibrillation compared to
      patients without. With this data and the good clinical results after BIV-ICD
      implantation, we consider the implantation of a BIV-ICD system in every patient
      with appropriate indications.

PMID- 11981704
TI  - Comparison of ultrasonic scalpel versus argon-beam and conventional
      electrocautery for internal thoracic artery dissection.
AB  - BACKGROUND: We used an ultrasonic scalpel (USS) and an argon beam coagulator
      (ABC) to test their effectiveness and feasibility in comparison to conventional
      electrocautery for Internal Thoracic Artery (ITA) takedown, time for takedown,
      number of clips, thermal impact, along with morphological integrity assessed by
      histology. PATIENTS AND METHODS: Ninety-three patients undergoing elective
      coronary bypass surgery were prospectively randomized into three groups. In
      thirty-one patients, either an ultrasonic scalpel (USS, group A), an argon-beam
      coagulator (ABC, group B) or conventional electrocautery (CEC, group C) was used
      for ITA harvesting. RESULTS: Harvest times for ITA takedown using CEC (16.7 +/- 6
      min) was significantly faster compared to ABC (21.6 +/- 8.1 min; p = 0.02) and
      USS (24.1 +/- 8.1 min; p < 0.001). There was no significant difference comparing
      harvest times of USS and ABC (p = 0.1). The number of hemostatic clips used was
      significantly lower when using USS (5.5 +/- 4.6 clips) compared to both CEC (16.6
      +/- 6.2 clips; p < 0.001) and ABC (20.4 +/- 6.5 clips; p < 0.001) and
      significantly lower using CEC compared to ABC (p < 0.007). There were no
      significant differences in bleeding points within the tissue bed among the groups
      (ABC 11/31 patients, CEC 11/31 patients and USS 12/31 patients). CONCLUSION: This
      study demonstrates that dissection of the ITA pedicle can be safely done with
      USS, ABC, and CEC. However, USS is associated with less hemostatic clip demand
      but prolonged harvest time compared it to ABC and CEC; histological assessment
      revealed no significant difference when comparing groups and equipment used. A
      variety in design of the hooks may probably ease ultracision practicability.

PMID- 11981705
TI  - VAMOS--ventilator assisted model for off-pump surgery.
AB  - BACKGROUND: Introduction of innovative cardiac procedures mostly depends on
      extensive evaluation using laboratory animal models. Avoiding living creatures in
      the experimental setup where possible without loss of reliability would be
      progressive from a logistical as wells as an ethical perspective. METHODS: Hearts
      of meat-production animals (pigs) were removed without structural damage. Two
      tracheotomy tubes (length 35 mm, diameter 10 mm) were inserted into aortic and
      pulmonal positions. The atrial inflow had to be ligated. The ventilation tubes
      were joined to a respirator. The "ventilation" frequency was limited to a maximum
      of 100/min, "inspiration" volume at 100 ml and ventilation pressure at up to 60
      mbar. RESULTS: "Air beats" triggered by the frequency of the respirator occurred
      in the ventilated heart. Insufflation and deflation generated movement that was
      almost the same as physiological action. CONCLUSIONS: Air-animation of the heart
      using a standard respirator is an easily conducted alternative to extensive and
      expensive laboratory experiments for development and quality control of new
      devices or techniques without compromising the scientific value of results and
      without using living animals.

PMID- 11981706
TI  - Cerebral oxygen monitoring during neonatal cardiopulmonary bypass and deep
      hypothermic circulatory arrest.
AB  - BACKGROUND: This study was undertaken to investigate the physiological effects of
      cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on
      cerebral oxygen metabolism estimated by near-infrared spectroscopy (NIRS).
      METHODS: Ten newborn piglets (2.1 to 2.6 kg) were monitored with right frontal
      NIRS; the right jugular bulb was cannulated for intermittent sampling of jugular
      venous blood. All animals underwent CPB, cooling to a core temperature below 15
      degrees C, 60 minutes of DHCA followed by subsequent reperfusion and rewarming.
      Continuously recorded NIRS data and intermittent jugular venous blood values were
      compared. RESULTS: NIRS performance was examined over the jugular venous oxygen
      saturation (SjvO2) range of 40 to 98 %, a linear correlation was found between
      SjvO2 and NIRS-derived regional cerebral oxygen saturation (rSO2) (r = 0.91, p <
      0.001). A correlation was observed between the cellular oxidation NIRS-parameter
      cytochrome oxidase aa3 (CytOx) slope during the DHCA period in relation to rectal
      and nasopharyngeal temperature immediately before the onset of DHCA (r = 0.75 and
      0.85, p < 0.001). CONCLUSIONS: This study suggests that NIRS-measured hemoglobin
      oxygenation parameters may reflect functional changes in cerebral hemodynamics
      and brain tissue oxygenation, while CytOx values represent related effects on
      intracellular oxidative metabolism.

PMID- 11981707
TI  - Operative procedure and volumetry in experimental biomechanical hearts.
AB  - BACKGROUND: To date, skeletal muscle ventricles (SMVs) have been integrated into
      the circulation by a second operation following construction, vascular delay and
      several weeks of electrical conditioning. Recently, intra-thoracic SMVs around a
      mock system contracted against a pressure of 70 mmHg for several months
      immediately after construction in the presence of clenbuterol. This indicates
      that the two-step procedure may be exchanged for a clinically favorable one-step
      operation. The stroke volume is tested intra-operatively. METHODS: In twelve Boer
      goats, the latissimus dorsi muscle was folded in a double layer around a
      polyurethane chamber, which was integrated into descending thoracic aorta. This
      muscular flow-through chamber containing a stabilizing inner layer denoted
      "Biomechanical Heart" (BMH) showed immediate activity against systemic pressure.
      The conductance catheter method was applied for analysis of intra-operative
      stroke volume. RESULTS: The one-step operative procedure employed was practicable
      in all 12 goats. Operative complications were eliminated without difficulty.
      Intraoperative application of the conductance catheter resulted in BMH with a
      stroke volume of 55 +/- 14 ml. In the best BMH on postoperative day 132, a
      continuous pumping capacity of 1.4 l/min was measured. This BMH functioned up to
      day 414 postoperatively, and failed due to a rupture of the pumping chamber.
      CONCLUSION: This operative procedure and dynamic volumetry of experimental
      Biomechanical Hearts might be relevant for clinical use.

PMID- 11981708
TI  - Mediastinitis and cardiac surgery--an updated risk factor analysis in 10,373
      consecutive adult patients.
AB  - BACKGROUND: Deep sternal wound infection (DSWI) remains a serious complication
      after cardiac surgery. New evolving techniques including the utilization of
      internal mammary arteries (IMA), beating heart procedures, and minimal invasive
      surgery (MIC) require an updated risk factor analysis to identify high risk
      patients in order to improve perioperative treatment. METHODS: 10,373 consecutive
      patients receiving cardiac surgery between May 1996 and August 1999 were
      evaluated: 9,303 underwent full sternotomy whereas a minimally invasive (MIC)
      approach using partial sternotomy or lateral thoracotomy was used in 1,070
      patients. DSWI was defined as the evidence of mediastinitis seen at reoperation
      along with one or more of the following: positive culture of mediastinal fluid,
      positive blood culture or temperature higher than 38 degrees C and/or
      leukocytosis. RESULTS: The overall incidence of DSWI in the "full sternotomy"
      group was 1.44 % (134 of 9,303). Univariate risk factor analysis showed a
      significant influence of IMA use, ICU / IC treatment > 5 days, postoperative
      ventilator time > or = 72 h, need for reexploration, diabetes, surgery time > or
      = 180 min, assist device implantation (including use of IABP), peripheral
      vascular disease and increased body mass index. Multivariate analysis identified
      double IMA, ICU treatment > 5 days, single IMA, diabetes, reexploration and
      increased body mass as significant risk factors. No mediastinitis was observed in
      the MIC group. CONCLUSION: As DSWI is related to sternotomy, a MIC approach
      should be considered for patients at high risk for DSWI. IMA takedown as a
      pedicled graft should be especially avoided in patients with diabetes since the
      risk for postoperative mediastinitis is unacceptably high in this patient group.

PMID- 11981709
TI  - Epicardial echocardiography for correct placement of the intracardial
      biventricular assist device (Impella).
AB  - BACKGROUND: Correct placement of the intracardial biventricular assist device
      (Impella) as a supporting system for off-pump coronary surgery is routinely
      checked by transesophageal echocardiography and invasive pressure measurements.
      However, it remains difficult to verify the accurate position of the right heart
      system when the posterior wall is exposed. METHODS: In 23 patients undergoing
      augmented beating heart CABG surgery, the correct placement of the lmpella-system
      was controlled by TEE as well as by a new 15-6 L epicardial echotransducer (EE)
      (Agilent, Andover, MA). RESULTS: TEE assisted well in inserting the system in all
      patients. The correct placement of the distal end of the right heart system 1.5
      cm behind the pulmonary valve was verified in 18/23 cases by TEE vs. 23/23 cases
      by EE. Dislocation of the devices during tilting of the heart could only be
      verified by EE. CONCLUSIONS: Epicardial echocardiography is a useful, innovative
      method for monitoring the correct placement of the new intracardial biventricular
      assist device during beating-heart surgery.

PMID- 11981710
TI  - Survival and quality of life after a long-term intensive care stay.
AB  - OBJECTIVE: The growing number of high-risk patients in cardiac surgery
      unavoidably leads to more complications, and therefore to a prolonged stay in an
      intensive care unit (ICU). The aim of our investigation was to elaborate on the
      fate of patents after long-term ICU treatment. METHODS: Out of 5055 patients, 232
      had to be treated for longer than 5 days in ICU. These 232 patients were analyzed
      for in-hospital mortality and followed up for quality of life. The Barthel
      mobility index and geriatric depression scale by Sheikh and Yesavage were used to
      evaluate physical ability and mood disturbances. Follow-up time was 82 months,
      and could be completed for 99 % of the patents. RESULTS: In-hospital mortality
      was 34.6 %, with the majority of cases being coronary artery bypass grafting
      procedures (59.9 %). Average stay in ICU was 12.0 days for the survivors and 17
      days for non-survivors. During follow-up time (6 - 82 months), another 56
      patients (23 %) died. Survivors (n = 98) were predominantly in NYHA classes l-ll
      (83 %) with a Barthel index of more than 80, representing adequate mobilization
      during daily life in 78 % of the patients. Results according to the geriatric
      depression scale were normal in the vast majority of patients (91 %) with severe
      or life threatening depressions in only 6 patients (8 %). CONCLUSION: Long-term
      treatment of critically ill patients is admittedly burdened with high in-hospital
      and follow-up mortality. However, the excellent physical and psychological
      recovery of survivors unequivocally supports the employment of all technical and
      personnel resources within modern intensive care medicine.

PMID- 11981711
TI  - Vacuum-assisted venous drainage in complex congenital cardiac surgery.
AB  - Here, we report on a case of temporary neurological damage following conduit
      replacement from the right ventricle to pulmonary artery during which vacuum
      assisted venous drainage was used. We will discuss the benefits and risks of this
      technique with potential arterial air embolism despite the use of arterial line
      filters. We will also make recommendations for avoiding such complications.

PMID- 11981712
TI  - Video-assisted repair of an eventrated left hemidiaphragm.
AB  - Video-assisted thoracoscopic surgery is emerging as a viable approach to
      increasingly complex intrathoracic therapeutic procedures. Here, we present a
      case of eventrated left hemidiaphragm caused by a blunt trauma in an elderly man.
      The diaphragm was repaired successfully using a video-assisted procedure, thus
      giving the patient the advantages of a minimally invasive operation.

PMID- 11981713
TI  - Esophageal melanotic schwannoma presenting with superior vena caval obstruction.
AB  - A rare tumor with an unusual presentation can pose a diagnostic and management
      dilemma. In this paper, we will discuss the management of a 47-year-old lady with
      melanotic schwanoma of the esophagus who presented with superior vena caval
      obstruction. The initial histological diagnosis of esophageal metastatic
      malignant melanoma did not corroborate the clinical and operative findings.
      Further evaluation revealed positivity for HMB45, S-100 protein, and vimentin,
      and confirmed the diagnosis of melanotic schwannoma.

PMID- 11981714
TI  - Late complications and shape changes of the endografts after gigantic thoracic
      aortic aneurysm repair over a 7-year follow-up.
AB  - This report details a 7 years follow up observations in a 71-year-old patient
      treated with custom made endograft for gigantic thoracic aortic aneurysm (TAA).
      Progressive changes of the thoracic aorta and aneurysm after endograft placement
      led to two late complications including proximal stent graft prolapse into the
      aneurysm and extreme kinking of the endograft and aorta 28 and 51 months after
      treatment, respectively. Both complications were successfully treated with new
      endografts placement. Percutaneous endovascular repair is a promising, minimally
      invasive alternative to exclude TAA. This technique allows long-term treatment of
      patients who are unsuitable for conventional surgical procedures.

PMID- 11981715
TI  - Pacemaker dislocation--truly ectopic activation necessitating surgical treatment.
AB  - Intra-abdominal migration of a generator from an epicardial pacemaker system is a
      rare but potentially life-threatening complication. We report on a case of a 2
      year-old child in whom the generator silently migrated from the sheath of the
      rectus abdominis muscle in the upper abdominal wall down into the peritoneal
      cavity. We advise that if there is any evidence of intra-abdominal migration, the
      generator should be properly repositioned without delay.

PMID- 11981716
TI  - Iatrogenic coronary artery fistula in a patient with a single coronary artery.
AB  - Here, we report on a case of coronary artery fistula that developed following the
      repair of a double-outlet right ventricle (DORV) with infundibular pulmonary
      stenosis in a patient who has a single coronary artery. The major concern in this
      case was that of reduction of coronary blood flow from the patient's only
      coronary artery to the myocardium distal to the fistula.

PMID- 11981717
TI  - Esophageal necrosis and perforation of the left main bronchus following
      photodynamic therapy of esophageal carcinoma.
AB  - Photodynamic therapy is an effective palliative treatment of esophageal cancer.
      Minor complications associated with this therapy include pleural effusions, fever
      or esophageal strictures. In addition to this major complications such as
      respiratory-esophageal fistula and bronchus perforation have been described. We
      report here our experience with a patient who developed a complete esophageal
      necrosis and perforation of the left main bronchus following photodynamic
      therapy. The surgical and intensive care management of the patient is described
      and the literature discussed.

PMID- 11981718
TI  - Gastrobronchial fistula repair followed by esophageal leak--rescue by
      transesophageal drainage of the pleural cavity.
AB  - A gastrobronchial fistula (GBF) associated with bilateral aspiration pneumonia
      was diagnosed six years after an esophagectomy with gastric pull-up. After failed
      surgical repair, an uncontained esophagopleural leak developed. Fistula closure
      was attempted by implanting a Wilson-Cook endoprosthesis, which quickly became
      dislodged. Transesophageal drainage was positioned endoscopically through the
      suture-line defect and led to closure of the leak after 10 days.

PMID- 11981719
TI  - Description of a reusable device for the temporary stenting of the open sternum.
AB  - BACKGROUND: Myocardial oedema, non-surgical bleeding and the use of mechanical
      assist devices following major heart surgery sometimes prevent primary closure of
      the sternum. METHOD: We describe a reusable sterile device for temporarily
      stenting the open sternum for safety. RESULTS: The sternal stent was used in 32
      patients for a mean time of 2 days. We observed no mediastinitis and no wound
      healing disorders. A secondary closure of the sternum was performed in 28
      patients. CONCLUSION: We present a device for sternal stenting that is reusable,
      easy to apply and allows a good handling of the critically ill patient due to its
      extreme stability.

PMID- 11981720
TI  - Coronary vein leads for cardiac pacing in patients with tricuspid valve
      replacement.
AB  - BACKGROUND: Because after tricuspid valve replacement (TVR) the transvenous
      implantation of endocardial leads is contraindicated, myocardial screw-in leads
      were used to ventricular pacing. Recently available coronary vein (CV) leads are
      stimulating the left ventricle epicardially and can be implanted transvenously,
      too. METHOD AND RESULTS: We implanted these leads in patients (pts) with TVR (n =
      7) or after valve repair (n = 1) without complications. In 7 pts we used bended
      CV leads with a microporous tip and only in one pt a CV lead with a stimulation
      via metal ring. The stimulation thresholds (ST) were stable in all pts.
      CONCLUSIONS: The use of CV leads offers a minimal invasive approach for permanent
      cardiac stimulation after TVR. Low chronic ST are resulting in an energy saving
      pacemaker mode. CV leads can be used after previous heart surgery as well as for
      difficult anatomical situations.

PMID- 11981721
TI  - Heparin in patients with HIT II requiring complex cardiac procedures.

PMID- 11981722
TI  - Mediastinitis after percutaneous dilatational tracheostomy.
AB  - In our experience, PDT after total arch replacement, especially after dissection
      of neck vessels, should be approached with caution. A long skin incision that
      allows discharge to drain from the wound and a sufficiently long postoperative
      tracheostomy period to allow tissue healing in the neck are necessary for
      prevention of mediastinitis.

PMID- 11981723
TI  - Nosocomial infections in left ventricular assist device recipients.
AB  - Infection remains a serious complication of left ventricular assist device (LVAD)
      implantation. We performed a cohort study to assess infections among patients who
      underwent LVAD implantation from October 1996 through May 1999. Thirty-six LVADs
      were implanted in 35 patients; the mean duration (+/- standard deviation) of LVAD
      use was 73+/-60 days (total for all patients, 2565 days). Sixteen patients
      developed surgical site infections (SSIs; rate, 6.2 infections per 1000 LVAD
      days); 9 were deep-tissue or organ/space infections and 7 were superficial. Other
      infections included 7 cases of pneumonia (rate, 2.7 cases per 1000 LVAD days), 6
      venous infections (rate, 2.3 per 1000 LVAD days), 2 bloodstream infections (rate,
      cases 0.8 per 1000 LVAD days), 3 urinary tract infections, and 2 skin and soft
      tissue infections. Deep SSIs were associated with the requirement for
      postoperative hemodialysis (P=.02). Overall use of antibiotics was extensive, and
      a trend toward infection with antibiotic-resistant organisms was noted.
      Infections were a frequent complication of LVAD implantation. Further studies of
      interventions for preventing infection in LVAD recipients are warranted.

PMID- 11981724
TI  - Effects of large dosages of amoxicillin/clavulanate or azithromycin on
      nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae,
      nonpneumococcal alpha-hemolytic streptococci, and Staphylococcus aureus in
      children with acute otitis media.
AB  - Prior use of antibiotics is associated with carriage of resistant bacteria.
      Colonization by Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal
      alpha-hemolytic streptococci (NPAHS), and Staphylococcus aureus was evaluated in
      children receiving antibiotic therapy for acute otitis media and in untreated,
      healthy control subjects. Children were randomly assigned to receive either
      amoxicillin/clavulanate (90 mg/kg per day) or azithromycin. Swabs were obtained
      before initiating therapy and again 2 weeks and 2 months after initiating
      therapy. We also obtained swabs from control subjects at the time of enrollment
      and 2 weeks and 2 months after enrollment. The decrease in the rate of carriage
      of S. pneumoniae and H. influenzae at 2 weeks was significant only in the
      amoxicillin/clavulanate group (P<.001 and P=.005, respectively). The rate of
      nasopharyngeal colonization with NPAHS among treated patients increased from 23%
      to 39% at 2 months (P=.01). This increase was similar for both treatment groups.
      These results suggest that the competitive balance between organisms is altered
      by antibiotic therapy.

PMID- 11981725
TI  - Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba
      hospitals.
AB  - Blastomyces dermatitidis is a dimorphic fungus endemic to Canada and the United
      States. Few reports regarding blastomycosis in Canada have been published. We
      retrospectively reviewed the medical charts of 143 patients with confirmed cases
      of blastomycosis diagnosed in hospitals in Manitoba, Canada, from 1988 through
      1999. The annual incidence rate of blastomycosis in Manitoba was 0.62 cases per
      100,000 population, compared with 7.11 cases per 100,000 population in the
      Kenora, Ontario district. The average age of patients was 38.0 years, and males
      accounted for 65.0% of cases. An increased incidence of blastomycosis was
      observed in the Aboriginal subpopulation. Organ systems involved were as follows:
      respiratory system (93.0% of cases), skin (21.0%), bone (13.3%), genitourinary
      tract (1.4%), and the central nervous system (1.4%); 6.3% of patients died, and
      death was associated with a short clinical course. This study provides a summary
      of the current status of blastomycosis in this area of endemicity in Canada.

PMID- 11981726
TI  - Malaria in injection drug abusers in Vietnam.
AB  - A prospective case-control study was conducted in a referral hospital in Ho Chi
      Minh City, Vietnam, to compare the clinical and laboratory features and outcome
      of severe falciparum malaria in injection drug abusers (IDAs) with those of
      patients who had acquired malaria by mosquito bite. From 1991 to 1996, 70 IDAs
      were admitted to the hospital, of whom at least 32 had acquired malaria by needle
      sharing. Although IDAs were more likely than control patients with severe malaria
      to be malnourished and to have coincident hepatitis B, hepatitis C, and human
      immunodeficiency virus infections, the overall rates of mortality, complications,
      and recovery were similar in the 2 groups. The route of malaria acquisition did
      not affect the outcome of severe malaria. The management of severe malaria in
      IDAs is similar to that for other patients.

PMID- 11981727
TI  - Influence of serogroup on the presentation, course, and outcome of invasive
      meningococcal disease in children in the Republic of Ireland, 1995-2000.
AB  - To test the hypothesis that the infecting meningococcal serogroup modulates the
      presentation, course, and outcome of invasive meningococcal disease (IMD), we
      performed a retrospective review of cases of IMD in 407 children from 2 tertiary
      referral centers and 2 regional centers in Ireland. Patients infected with
      serogroup C meningococci (n=104) were older than those infected with serogroup B
      (n=303; median, 2.5 vs. 1.5 years; P=.04); all other demographic and clinical
      parameters were similar for the 2 groups. Among serogroup B patients, mortality
      was 3.6% and morbidity was 10%; for serogroup C patients, mortality was 4.8% and
      morbidity was 12.5% (P=.81 and P=.76, respectively). Serogroup C-associated
      sequelae more often were multiple (P=.003). Despite the introduction of serogroup
      C conjugate vaccine into the routine immunization schedule of some countries,
      ongoing morbidity from IMD is anticipated, because group B disease was very
      similar to group C disease in this pediatric population.

PMID- 11981728
TI  - Spotless rickettsiosis caused by Rickettsia slovaca and associated with
      Dermacentor ticks.
AB  - The pathogenic role of Rickettsia slovaca was first demonstrated in 1997 in a
      patient who presented with a single inoculation lesion of the scalp and enlarged
      cervical lymph nodes after receiving a bite from a Dermacentor tick.
      Subsequently, we evaluated the occurrence of R. slovaca infections among patients
      living in France and Hungary who presented with these symptoms. R. slovaca
      infections were confirmed by polymerase chain reaction (PCR) in 17 of 67 enrolled
      patients. Infections were most likely to occur in patients aged <10 years and in
      patients who were bitten during the colder months of the year. The median
      duration of incubation for the disease was 7 days. Fever was present in only 2
      patients, and only 1 patient developed a rash. Sequelae included persistent
      asthenia (3 cases) and localized alopecia (4 cases). Immunofluorescence and/or
      Western blot analysis detected antibodies in 50% of tested patients. Three
      Dermacentor ticks obtained from patients revealed R. slovaca by PCR.

PMID- 11981729
TI  - Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection
      in solid-organ transplant recipients.
AB  - The resistance of cytomegalovirus (CMV) to ganciclovir is a factor in therapeutic
      failure and disease progression. The clinical significance of such resistance in
      solid-organ transplantation has not been completely established. Six patients who
      developed persistent infection due to ganciclovir-resistant CMV were treated with
      a combination of ganciclovir (50% of the therapeutic dose) and a daily dose of
      intravenous foscarnet that gradually increased to a maximum of 125 mg/kg. All
      patients responded clinically within 72-96 hours. Magnesium depletion occurred in
      all patients. No clinical or laboratory relapses have been observed in 6-30
      months of follow-up. Gradually increasing doses of foscarnet combined with half
      dose regimens of ganciclovir are safe and can be beneficial in organ transplant
      recipients with ganciclovir-resistant CMV infection. Larger studies are needed to
      identify the patients who are most likely to benefit from this regimen.

PMID- 11981730
TI  - Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area
      hospitals.
AB  - We report a retrospective study of 253 patients with vertebral osteomyelitis (VO)
      who had long-term follow-up. Eleven percent of the patients died, residual
      disability occurred in more than one-third of the survivors, and relapse occurred
      in 14%. Median duration of follow-up was 6.5 years (range, 2 days to 38 years).
      Independent risk factors for adverse outcome (death or qualified recovery) were
      neurologic compromise, time to diagnosis, and hospital acquisition of infection
      (P< or =.004). Surgical treatment resulted in recovery or improvement in 86 (79%)
      of 109 patients. Magnetic resonance images (110 patients) were often obtained
      late in the course of infection and did not significantly affect outcome. Often,
      relapse developed in individuals with severe vertebral destruction and abscesses,
      appearing some time after surgical drainage or debridement. Recurrent bacteremia,
      paravertebral abscesses, and chronically draining sinuses were independently
      associated with relapse (P< or =.001). An optimal outcome of VO requires
      heightened awareness, early diagnosis, prompt identification of pathogens,
      reversal of complications, and prolonged antimicrobial therapy.

PMID- 11981731
TI  - The role of serum antibodies in the protection against rotavirus disease: an
      overview.
AB  - A critical observation in understanding immunity to rotavirus is that children
      infected with wild virus or vaccinated with oral live vaccines develop a humoral
      immune response and are protected against severe disease upon reinfection.
      Nevertheless, much controversy exists as to whether these serum antibodies are
      directly involved in protection or merely reflect recent infection, leaving the
      protective role to mucosal or cell-mediated immunity or to other as-yet-undefined
      mechanisms. We have reviewed data from a variety of studies in humans, including
      challenge experiments in adult volunteers, longitudinal studies of rotavirus
      infection in young children, and clinical trials of animal and animal-human
      reassortant rotavirus vaccines in infants. These data suggest that serum
      antibodies, if present at critical levels, are either protective themselves or
      are an important and powerful correlate of protection against rotavirus disease,
      even though other host effectors may play an important role as well.

PMID- 11981732
TI  - The promise of novel technology for the prevention of intravascular device
      related bloodstream infection. II. Long-term devices.
AB  - Intravascular devices (IVDs) are widely used for vascular access but are
      associated with a substantial risk of IVD-related bloodstream infection (BSI).
      The development of novel technologies based on our understanding of pathogenesis
      promises a quantum reduction in IVD-related infections in an era of growing
      nursing shortage. Infections of long-term IVDs (most are in place for > or =10
      days), including cuffed and tunneled central venous catheters (CVCs), implanted
      subcutaneous central venous ports, and peripherally inserted central catheters
      (PICCs), are primarily due to microorganisms that gain access to the catheter hub
      and lumen. Novel securement devices and antibiotic lock solutions have been shown
      to reduce the risk of IVD-related BSI in prospective randomized trials. The
      challenge for the future will be to identify new preventative technologies and to
      begin to more-widely adapt those technologies that have already been shown to be
      efficacious and cost effective.

PMID- 11981733
TI  - Prevention of yellow fever in persons traveling to the tropics.
AB  - Yellow fever (YF) is a potentially lethal mosquito-borne viral hemorrhagic fever
      endemic in Africa and South America. Nine million tourists annually arrive in
      countries where YF is endemic, and fatal cases of YF have occurred recently in
      travelers. In this article, we review the risk factors for YF during travel and
      the use of YF 17D vaccine to prevent the disease. Although the vaccine is highly
      effective and has a long history of safe use, the occurrence of rare, fatal
      adverse events has raised new concerns. These events should not deter travelers
      to areas where YF is endemic from being immunized, because the risk of YF
      infection and illness may be high in rural areas and cannot be easily defined by
      existing surveillance. To avoid unnecessary vaccination, physicians should
      vaccinate persons at risk on the basis of knowledge of the epidemiology of the
      disease, reports of epidemic activity, season, and the likelihood of exposure to
      vector mosquitoes.

PMID- 11981734
TI  - Rhodococcus equi: an emerging pathogen.
AB  - More than 100 cases of Rhodococcus equi infection have been reported since the
      first description of human disease caused by this organism. The vast majority of
      patients infected with R. equi are immunocompromised, and two-thirds have human
      immunodeficiency virus infection. The clinical manifestations of R. equi
      infection are diverse, although 80% of patients have some pulmonary involvement.
      The organism is easily cultured from specimens of infected tissue or body fluid,
      but it may be misdiagnosed as a contaminant. Treatment is often prolonged, and
      relapses at distant sites are common. This article summarizes the history,
      diagnosis, clinical features, and treatment of infection with this emerging
      pathogen.

PMID- 11981735
TI  - Antifungal chemoprophylaxis after blood and marrow transplantation.
AB  - Invasive fungal infections are common and deadly in recipients of blood and
      marrow transplants. Current diagnostic techniques do not allow accurate early
      diagnosis, especially of infection with mould pathogens, and delays in diagnosis
      are associated with treatment failure. This lack of early diagnosis has provided
      the impetus for the development of antifungal prophylaxis. Fluconazole
      prophylaxis is highly effective for the control of invasive yeast infections and
      associated with few breakthrough infections. The development of antimould
      prophylaxis in this patient population is a high priority.

PMID- 11981736
TI  - Can antiretroviral therapy be used to prevent sexual transmission of human
      immunodeficiency virus type 1?
AB  - Approximately 5 million people annually are newly infected with human
      immunodeficiency virus (HIV). Although education, behavior modification, and
      promotion of condom use are effective transmission-prevention measures, the
      severity of the pandemic demands that all possible prevention strategies be
      explored. Antiretroviral therapy has the potential to decrease sexual
      transmission of HIV type 1 by reducing levels of HIV RNA and thus decreasing the
      risk that infected persons will transmit the disease or by its use as preexposure
      or postexposure prophylaxis. In this article, we explore the rationale for using
      antiretroviral therapy to prevent sexual transmission of HIV, as well as the
      limitations of this approach.

PMID- 11981737
TI  - Factors related to lipodystrophy and metabolic alterations in patients with human
      immunodeficiency virus infection receiving highly active antiretroviral therapy.
AB  - Morphologic and metabolic changes associated with protease inhibitor (PI) therapy
      have been reported since the introduction of PIs for treatment of human
      immunodeficiency virus infection. These changes were measured 12-20 months after
      initiation of PI therapy in a cross-sectional study involving 614 patients from
      the Antiproteases Cohorte (APROCO) Study (Agence Nationale de Recherches sur le
      Sida-EP11). The prevalence was 21% for isolated peripheral atrophy, 17% for
      isolated fat accumulation, 24% for mixed syndrome, 23% for glucose metabolism
      alterations, 28% for hypertriglyceridemia (triglyceride level, > or =2.2 mM), and
      57% for hypercholesterolemia (cholesterol level, > or =5.5 mM). Age was
      significantly associated with different phenotypes of lipodystrophy and metabolic
      alterations, but body-mass index, CD4(+) cell count, and type of nucleoside
      reverse-transcriptase inhibitor or PI received were not constantly associated
      with these changes. Furthermore, in all models tested, exposure to stavudine was
      associated with lipoatrophy and exposure of ritonavir was associated with
      hypertriglyceridemia. Detection and management of these disorders should be
      implemented to prevent further complications.

PMID- 11981738
TI  - Prevalence, incidence, and persistence or recurrence of trichomoniasis among
      human immunodeficiency virus (HIV)-positive women and among HIV-negative women at
      high risk for HIV infection.
AB  - Trichomoniasis has been implicated in the acquisition and transmission of human
      immunodeficiency virus (HIV) infection. The prevalence, incidence, and
      persistence or recurrence of trichomoniasis were assessed among HIV-positive
      women and among HIV-negative women at high risk for HIV infection. A total of 871
      HIV-seropositive women and 439 HIV-seronegative women enrolled in the HIV
      Epidemiology Study (HERS) were seen biannually. The prevalence of trichomoniasis
      was 9.4%-29.5% among HIV-seropositive women and 8.2%-23.4% among HIV-seronegative
      women. Prevalence decreased over time, did not vary according to HIV status or
      CD4 cell count, and was higher among women who reported crack use (P=.02) or
      cigarette use (P=.02), women who had bacterial vaginosis (P=.02), and those who
      were black (compared with white women, P<.001). There were no differences,
      according to HIV status or CD4 cell count, in the adjusted incidence, unadjusted
      incidence, or persistence or recurrence of trichomoniasis. HIV infection does not
      make a woman more likely to have prevalent, incident, or persistent or recurrent
      trichomoniasis.

PMID- 11981739
TI  - Linezolid treatment for osteomyelitis due to vancomycin-resistant Enterococcus
      faecium.
AB  - The incidence of nosocomial infections caused by vancomycin-resistant enterococci
      has risen substantially during the past 15 years. We report the use of linezolid
      for the successful treatment of hip prosthesis infection associated with
      osteomyelitis due to vancomycin-resistant Enterococcus faecium.

PMID- 11981740
TI  - Progressive cutaneous hyalohyphomycosis due to Paecilomyces lilacinus: rapid
      response to treatment with caspofungin and itraconazole.
AB  - A case of rapidly progressive cutaneous infection due to Paecilomyces lilacinus
      developed in a woman with advanced pancreatic cancer who did not have
      granulocytopenia. The infection responded favorably to caspofungin and
      itraconazole combination therapy.

PMID- 11981741
TI  - Predicting the emergence of antimicrobial resistance.

PMID- 11981743
TI  - Antiviral pathway activation in chronic fatigue syndrome and acute infection.

PMID- 11981745
TI  - Influenza surveillance with rapid diagnostic tests.

PMID- 11981746
TI  - Cutaneous inoculation blastomycosis.
AB  - Cutaneous inoculation blastomycosis is a rare illness. We report a case of
      cutaneous inoculation blastomycosis in a patient who was inoculated after being
      struck by a projectile while performing yard work. We also review cases of
      cutaneous inoculation blastomycosis described elsewhere, to improve
      characterization of the syndrome.

PMID- 11981747
TI  - Acute terminal ileitis associated with pneumococcal bacteremia: case report and
      review of pneumococcal gastrointestinal diseases.
AB  - In this report, we describe a patient with acute terminal ileitis due to
      Streptococcus pneumoniae, review 3 previously reported cases of isolated
      enteritis due to S. pneumoniae, and summarize the English-language literature on
      primary and secondary pneumococcal gastrointestinal diseases. Various theories
      have been advanced to explain the pathogenesis of this rare and potentially life
      threatening form of pneumococcal infection, but the mechanism by which S.
      pneumoniae causes gastrointestinal disease is still unknown.

PMID- 11981749
TI  - Molecular aspects of iron absorption: Insights into the role of HFE in
      hemochromatosis.
AB  - Hereditary hemochromatosis is the most common genetic disorder occurring in
      persons of northern European descent, and the clinical hallmark of the disease is
      the gradual accumulation of iron in internal organs, especially the liver, heart,
      and pancreas, which ultimately leads to organ failure. HFE, the gene that is
      defective in the majority of cases, was identified in 1996 and, although the
      exact role that HFE plays in the uptake and utilization of iron is not yet clear,
      important aspects of HFE function are emerging. Identification and studies of new
      proteins involved in the absorption of iron in the gut and in somatic cells has
      led to a clearer picture of how humans absorb iron from the diet and regulate
      this absorption to meet metabolic needs and to balance body iron stores. This
      review focuses on the molecular aspects of iron absorption and the role that HFE
      may play in these processes.

PMID- 11981750
TI  - Mechanism of action of ribavirin in the combination treatment of chronic HCV
      infection.

PMID- 11981751
TI  - Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis
      and fibrogenesis in experimental cirrhosis.
AB  - Cirrhosis consists of hepatocyte nodules surrounded by a highly vascularized
      fibrous tissue. We previously showed that the development of biliary cirrhosis in
      the rat is associated with the occurrence of hepatocellular hypoxia and the
      induction of hepatic angiogenesis. We herein examined the occurrence of hypoxia
      in an experimental model of diethylnitrosamine (DEN)-induced cirrhosis. We also
      determined whether hypoxia directly affects the expression of vascular
      endothelial growth factor (VEGF), of VEGF receptors (Flt-1, Flk-1), and of type I
      and type IV collagens in activated hepatic stellate cells (HSCs) and the
      expression of VEGF in hepatocytes. Our results show that in DEN-treated rats,
      although the progression of liver fibrosis is associated with hepatocellular
      hypoxia and angiogenesis, VEGF and Flt-1 expressions in the liver are increased
      and correlated with the density of microvessels. In vitro, hypoxia induces the
      expression of VEGF, Flt-1, and type I collagen in activated HSCs and that of VEGF
      in hepatocytes. In addition, we show that hypoxia-induced type I collagen
      expression in HSCs may occur independently of transforming growth factor beta1
      (TGF-beta1) overexpression. In conclusion, the present study provides further
      evidence that hepatocellular hypoxia and angiogenesis progress together with
      fibrogenesis after liver injury and that hypoxia directly contributes to the
      progression of liver fibrosis.

PMID- 11981752
TI  - Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-beta soluble
      receptor: implications for antifibrotic therapy.
AB  - Transforming growth factor (TGF) beta isoforms (in particular, TGF-beta1) play a
      central role in the fibrogenic response to injury in many organs, including the
      liver. Although TGF-beta is clearly important in fibrogenesis, a number of issues
      related to therapeutic antagonism have emerged. For example, the long-term effect
      of TGF-beta antagonism is unknown; furthermore, controversy exists as to
      appropriate levels of TGF-beta inhibition. Therefore, we aimed to examine TGF
      beta in models of chronic liver injury and to determine whether an in vivo dose
      response relationship exists for inhibition of TGF-beta. Liver injury was induced
      in BALB/c mice by administering carbon tetrachloride for 4 or 8 weeks. TGF-beta
      binding was inhibited with a soluble TGF-beta type II receptor (STR) construct,
      administered intraperitoneally over a dose range of 4.0, 1.0, 0.4, or 0.1 mg/kg
      twice weekly during fibrogenesis. Fibrogenesis was assessed by measurement of
      type I collagen messenger RNA (mRNA) expression and by quantitative morphometric
      analysis. In the 4-week study, STR at concentrations of 4.0, 1.0, and 0.1 mg/kg
      reduced type I collagen mRNA expression by 31%, 49%, and 60% compared with
      immunoglobulin (Ig) G controls, respectively. In the 8-week study, lower
      concentrations of STR (0.1 mg/kg) also had the greatest effect on type I collagen
      mRNA expression. Quantitative morphometrics similarly showed that lower
      concentrations of STR were the most antifibrogenic. In conclusion, the results
      confirm the antifibrotic effect of inhibiting TGF-beta in chronic hepatic
      wounding and, moreover, show that its in vivo effect in the mouse is dose
      dependent. Such findings have major translational implications for therapeutic
      strategies aimed at TGF-beta.

PMID- 11981753
TI  - Transport of the sulfated, amidated bile acid, sulfolithocholyltaurine, into rat
      hepatocytes is mediated by Oatp1 and Oatp2.
AB  - The uptake of the sulfated bile acid sulfolithocholyltaurine (SLCT) was
      investigated in isolated rat hepatocytes and in HeLa cells transfected with
      complementary DNAs (cDNAs) of organic anion transporting polypeptides (Oatps) 1
      and 2 cloned from rat liver. In hepatocytes, transport of SLCT was greatly
      reduced by bromosulfophthalein (BSP), estrone sulfate, the precursor bile acids
      cholyltaurine and lithocholyltaurine, and 4,4'-diisothiocyanostilbene-2-2'
      disulfonic acid (DIDS). However, SLCT transport was insensitive to 4
      methylumbelliferyl sulfate, harmol sulfate, digoxin, fexofenadine, and lack of
      sodium ion. Because the estimation of kinetic constants was enhanced with use of
      inhibitors, BSP (1-50 micromol/L) was added to isolated rat hepatocytes to assess
      the various transport components for SLCT uptake. The resulting data showed a
      nonsaturable pathway and at least 2 pathways of different Michaelis-Menten
      constants (K(m)) (70 and 6 micromol/L) and similar maximum velocities (V(max))
      (1.73 and 1.2 nmol/min/mg protein) and inhibition constants of 0.63 and 10.3
      micromol/L for BSP. In expression systems, SLCT was taken up by Oatp1 and Oatp2
      expressed in HeLa cells with similar K(m) values (12.6 +/- 6.2 and 14.6 +/- 1.9
      micromol/L). These K(m) values were comparable to that observed for the high
      affinity pathway in rat hepatocytes. In conclusion, the results suggest that
      transport of SLCT into rat liver is mediated in part by Oatp1 and Oatp2, high
      affinity pathways, a lower-affinity pathway of unknown origin, and a nonsaturable
      pathway that is compatible with a transport system of high K(m) and/or passive
      diffusion.

PMID- 11981754
TI  - Ursodeoxycholate and tauroursodeoxycholate inhibit cholangiocyte growth and
      secretion of BDL rats through activation of PKC alpha.
AB  - Accumulating bile acids (BA) trigger cholangiocyte proliferation in chronic
      cholestasis. The aim of this study was to determine if ursodeoxycholate (UDCA) or
      tauroursodeoxycholate (TUDCA) chronic feeding prevents the increased
      cholangiocyte growth and secretion in bile duct-ligated (BDL) rats, if UDCA and
      TUDCA effects are associated with increased cholangiocyte apoptosis, and to
      determine if this inhibition is dependent on increased intracellular Ca(2+)
      ([Ca(2+)](i)) and activation of protein kinase C (PKC) alpha. Immediately after
      BDL, rats were fed UDCA or TUDCA (both 275 micromol/d) for 1 week. We determined
      the number of bile ducts in liver sections, cholangiocyte proliferation (by
      measurement of H(3) histone and proliferating cellular nuclear antigen in
      isolated cholangiocytes), and ductal secretion. In purified cholangiocytes from 1
      week BDL rats, we evaluated if UDCA and TUDCA directly inhibit cholangiocyte
      proliferation and secretin-stimulated adenosine 3', 5'-monophosphate levels. We
      determined if UDCA and TUDCA activate PKC, increase [Ca(2+)](i), and alter the
      apical BA transporter (ABAT) expression in cholangiocytes. UDCA and TUDCA
      inhibited in vivo the cholangiocyte proliferation, secretion, and ABAT
      expression. In vitro UDCA and TUDCA inhibition of cholangiocyte growth and
      secretion required increased [Ca(2+)](i) and PKC alpha. In conclusion, activation
      of Ca(2+)-dependent PKC alpha is required for UDCA and TUDCA inhibition of
      cholangiocyte growth and secretion. Reduced cholangiocyte ABAT may decrease
      endogenous BA stimulation of cholangiocyte growth and secretion.

PMID- 11981755
TI  - Mallory body--a disease-associated type of sequestosome.
AB  - Mallory bodies (MBs) consist of abnormal keratins, ubiquitin, heat shock
      proteins, and the protein p62. p62 is encoded by an immediate-early response gene
      that rapidly responds to a variety of extracellular signals involved in cell
      proliferation, differentiation, and particularly oxidative stress. It acts as an
      adapter in signal transduction and binds noncovalently to ubiquitin, possibly
      being involved in the regulation of the fate of ubiquitinated proteins by
      segregation (i.e., sequestosome or aggresome formation). The presence of p62
      together with ubiquitinated abnormal keratins in the MB characterizes MBs as a
      disease-associated type of sequestosome. A detailed study on the expression of
      p62 and its relationship to MB formation in the 3,5-diethoxycarbonyl-1,4
      dihydrocollidine (DDC)-treated mouse liver is reported based on
      immunohistochemical, immunoblot, and Northern blot analyses. The results indicate
      that p62 is rapidly induced in hepatocytes of intoxicated animals preceding MB
      formation. As suggested by experiments with short-term DDC-treated naive mice and
      mice refed DDC after recovery from long-term DDC treatment (primed mice), p62
      does not exert an initiating effect on MB formation but the appearance of MBs
      requires the presence of abnormal keratins, which associate with p62 after
      ubiquitination. The rapid induction of p62 and its association with MBs further
      support the role of oxidative stress in MB formation. In conclusion, the constant
      presence of p62 in MBs suggests that binding of p62 to abnormal keratins may
      allow hepatocytes to dispose potentially harmful proteins in a biologically inert
      manner.

PMID- 11981756
TI  - The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the
      intracellular localization of CDC25A in mice regenerating livers.
AB  - Liver cells from p21(Cip1-/-) mice subjected to partial hepatectomy (PH) progress
      into DNA synthesis faster than those from wild-type mice. These cells also show a
      premature induction of cyclin E/cyclin-dependent kinase (CDK) 2 activity. We
      studied the mechanisms whereby cells lacking p21(Cip1) showed a premature
      induction of this activity. Whereas the levels of CDK2, cyclin E, and p27(Kip1)
      were similar in both wild-type and p21(Cip1-/-) mice, those of the activator
      CDC25A were much higher in p21(Cip1-/-) quiescent and regenerating livers than in
      wild-type animals. Moreover, p21(Cip1-/-) cells also showed a premature
      translocation of CDC25A from cytoplasm into the nucleus. The ectopic expression
      of p21(Cip1) into mice embryo fibroblasts from p21(Cip1-/-) mice decreased the
      levels of CDC25A and delayed its nuclear translocation. The levels of CDC25A
      messenger RNA in p21(Cip1-/-) cells were higher than in wild-type cells,
      suggesting that this increase might be responsible, at least in part, for the
      high levels of CDC25A protein in these cells. Thus, the results reported here
      indicate that p21(Cip1) regulates the levels and the intracellular localization
      of CDC25A. We also found a good correlation between CDC25A nuclear translocation
      and cyclin E/CDK2 activation. In conclusion, premature translocation of CDC25A to
      the nucleus might be involved in the advanced induction of cyclin E/CDK2 activity
      and DNA replication in cells from animals lacking p21(Cip1).

PMID- 11981757
TI  - A tamoxifen-inducible chimeric Cre recombinase specifically effective in the
      fetal and adult mouse liver.
AB  - The spatiotemporal control of somatic mutagenesis in mice is considered a
      promising step to determine the function of a given gene product in a defined
      population of cells at any given time during animal life and also to generate
      better mouse models of human diseases. To introduce defined mutations in a
      temporally controlled manner in the liver, we established transgenic mice
      expressing a tamoxifen-inducible Cre recombinase under the control of the
      transthyretin promoter (TTR-Cre ind). The recombinase activity was examined on 2
      different floxed alleles by crossing TTR-Cre ind mice with either the reporter
      strain ROSA 26 or with homozygous mice carrying floxed catalytic alpha2 subunit
      of the adenosine monophosphate (AMP)-activated protein kinase gene. By placing 2
      mutated hormone-binding domains of murine estrogen receptor (Mer) at both termini
      of the Cre, we show that the fusion protein is active only on administration of
      the synthetic estrogen antagonist 4-hydroxytamoxifen (4-OHT) without any
      background in the absence of the inducing agent. The recombination is specific of
      the fetal and adult liver, and we show that the efficiency of recombination
      reached 80% to 100% after treatment with 4-OHT. In conclusion, TTR-Cre ind
      transgenic mice represent a valuable tool for temporally controlling the desired
      gene modifications in vivo in the fetal and adult liver. This would certainly
      help to understand the physiologic functions of genes in the liver, to create
      various mouse models mimicking human diseases, and to contribute to liver cancer
      specific suicide gene therapy studies.

PMID- 11981758
TI  - Extended preservation of rat liver graft by induction of heme oxygenase-1.
AB  - Livers can be preserved only for a short period without jeopardizing the
      transplantation outcome. Heat shock proteins (HSPs) protect against ischemia and
      reperfusion injury. We studied whether their induction and, in particular, the
      induction of heme oxygenase 1 (HO-1), improves transplantation survival after an
      extended time of cold storage. Rats were subjected to heat preconditioning (42
      degrees C for 20 minutes). Livers were harvested 24 hours later, preserved in
      cold University of Wisconsin solution for 44 hours, and transplanted in isogeneic
      rats (arterialized transplantation). HO-1 was specifically induced and inhibited
      by cobalt protoporphyrin and tin protoporphyrin, respectively. All animals
      receiving a graft without preconditioning and subjected to 44 hours of cold
      preservation died within 3 days, whereas 89% of rats who received a graft exposed
      to heat survived for 3 weeks (P =.0004). Preconditioning reduced serum aspartate
      transaminase (AST) and lactate dehydrogenase activities after reperfusion,
      improved bile flow, and decreased the histologic lesions of reperfusion injury.
      These significant effects of heat preconditioning were prevented by
      administration of tin protoporphyrin and could be reproduced by administration of
      cobalt protoporphyrin. In grafts without preconditioning, only a small fraction
      (<5%) of hepatocytes were positive with the terminal deoxynucleotide transferase
      mediated dUTP nick-end labeling (TUNEL) assay, and even less expressed activated
      caspase 3. Preconditioning tended to reduce the number of positive cells and to
      stimulate the expression of antiapoptotic Bcl-X(L). In conclusion, heat
      preconditioning and, specifically, overexpression of HO-1 improve
      posttransplantation survival and graft function after prolonged cold ischemia
      preservation. The mechanism underlying these beneficial effects does not appear
      to be prevention of apoptosis.

PMID- 11981759
TI  - Role of CCR2 in macrophage migration into the liver during acetaminophen-induced
      hepatotoxicity in the mouse.
AB  - The biological effects of monocyte chemoattractant protein (MCP) 1 are mediated
      by binding to C-C chemokine receptor (CCR) 2. In the present studies, we used
      CCR2 knockout (CCR2-/-) mice to examine the role of MCP-1 in acetaminophen
      induced macrophage accumulation in the liver, expression of inflammatory
      cytokines, and hepatotoxicity. We found that hepatic expression of CCR2 and MCP-1
      was increased 10-fold and 20-fold, respectively, 12 to 72 hours after
      administration of acetaminophen to wild-type mice. Expression of these proteins
      was localized in centrilobular regions of the liver. Whereas MCP-1 was expressed
      by both hepatocytes and macrophages, CCR2 was identified in inflammatory
      macrophages. F4/80 is a marker of mature macrophages expressed in large
      quantities by Kupffer cells. In wild-type mice, a 75% decrease in F4/80-positive
      macrophages was observed 24 to 48 hours after administration of acetaminophen. In
      contrast, expression of macrosialin (CD68), a marker of activated macrophages,
      increased 2-fold 24 to 72 hours after administration of acetaminophen and was
      associated with inflammatory cells. Although there was a decrease in the overall
      severity of inflammation and in the number of macrosialin-positive macrophages 72
      hours after administration of acetaminophen in CCR2-/- mice, the number of F4/80
      positive cells did not change. Loss of CCR2 was also found to alter acetaminophen
      induced expression of tumor necrosis factor alpha, monocyte chemoattractant
      protein 3, and KC/gro. However, the overall outcome of acetaminophen-induced
      hepatic injury was not affected. In conclusion, these data indicate that MCP-1
      and CCR2 contribute to the recruitment of a subset of activated macrophages into
      the liver during acetaminophen-induced hepatotoxicity that may be important in
      resolution of tissue injury.

PMID- 11981760
TI  - Endostatin inhibits murine colon carcinoma sinusoidal-type metastases by
      preferential targeting of hepatic sinusoidal endothelium.
AB  - An angiogenic response originating from peritumoral sinusoids and portal tracts
      that leads to the formation of metastases with sinusoidal- and portal-type
      angiogenic patterns, respectively, occurs during the course of liver colonization
      by murine 51b colon carcinoma (51b-CC) cells. We found a 5-fold increase in
      endogenous endostatin levels from hepatic blood over baseline (25 +/- 6 ng/mL)
      when micrometastatic foci had a detectable size and a 14-fold increase when
      macrometastases were developed. Despite this endogenous endostatin production,
      subcutaneous administration of recombinant human endostatin (rh-E; 50 mg/kg)
      decreased metastasis number by 60% when dosed from days 1 to 20 after 51b-CC cell
      injection, by 40% when given from days 10 to 20, and by 30% when administered as
      a single dose 30 minutes before 51b-CC cell injection compared with controls. In
      addition, administration of rh-E from days 10 to 20 decreased overall metastasis
      volume by 90% compared with controls. rh-E increased the number of necrotic
      sinusoidal-type metastases by 7-fold and decreased their intrametastatic CD31(+)
      microvessel density by 80% without affecting portal-type metastases. Flow
      cytometry showed rh-E binding to mouse liver sinusoidal cells but not to CD45(+)
      cells (leukocytes and Kupffer cells) or 51b-CC cells. Furthermore, rh-E induced
      sinusoidal endothelium cell apoptosis. In conclusion, despite the direct
      correlation between metastasis development and endogenous endostatin generation
      in the liver, administration of rh-E inhibited micrometastasis generation and
      macrometastasis growth very efficiently. The antiangiogenic mechanism was
      selective for sinusoidal-type metastases, in which the neovasculature originating
      from sinusoidal endothelium cells was targeted by rh-E.

PMID- 11981761
TI  - Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human
      hepatoma cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX)
      activity and are considered to exert antitumor actions in a variety of cancer
      cells, although the effects are unlikely entirely due to COX inhibition. Because
      clinical observations suggest that hepatocyte growth factor (HGF) can promote
      metastasis of hepatoma cells while stimulating tumor invasiveness, we
      investigated the effect of aspirin and NS-398, a selective COX-2 inhibitor, on
      HGF-mediated invasiveness of HepG2 human hepatoma cells. HGF stimulated the
      invasiveness of HepG2 cells in Matrigel cell invasion assay, together with
      increased expression of matrix metalloproteinase (MMP) 9. Addition of aspirin or
      NS-398, similar to PD98059, which acts as a specific inhibitor of mitogen
      activated protein kinase/extracellular signal-regulated kinase (MEK), an upstream
      kinase regulating extracellular signal-regulated kinase (ERK)1/2, abrogated such
      actions of HGF without affecting cell viability. Aspirin and NS-398, in contrast
      to PD98059, did not suppress ERK1/2 phosphorylation induced by HGF. However, both
      agents inhibited the kinase activity of ERK1/2 induced by HGF and repressed HGF
      induced phosphorylation of 90-kd ribosomal S6 kinase (RSK) and Elk-1, key
      downstream substrates of ERK1/2, resulting in the suppression of transcriptional
      activity of Elk-1 as well as nuclear factor kappaB (NF-kappaB) and AP-1, which
      are involved in MMP-9 gene regulation. In conclusion, our results suggest that
      aspirin and NS-398 inhibit HGF-induced invasiveness of HepG2 human hepatoma cells
      through ERK1/2.

PMID- 11981762
TI  - Effects of Sho-Saiko-to on hepatocarcinogenesis and 8-hydroxy-2'-deoxyguanosine
      formation.
AB  - Oxidative stress plays an important role in hepatocarcinogenesis. Although Sho
      saiko-to (TJ-9), a Japanese herbal medicine which has been recently administered
      to patients with chronic liver disease in Japan, prevents hepatocarcinogenesis,
      the mechanism by which TJ-9 protects against cancer development is not fully
      understood. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a DNA adduct by reactive oxygen
      species, is known as a parameter of genetic risk for hepatocarcinogenesis. To
      clarify whether the preventive effect on hepatocarcinogenesis by TJ-9 is
      dependent on 8-OHdG, the effect on 8-OHdG levels by TJ-9 was examined by using
      high-performance liquid chromatography-mass spectrometry (LC-MS) in a
      diethylnitrosamine (DEN)-induced hepatocarcinogenesis model of male Fisher rats.
      TJ-9 reduced the number of preneoplastic cells, detected as the glutathione S
      transferase P (GST-P)-positive hepatocytes, and inhibited the development of
      liver tumors. TJ-9 also significantly decreased the formation of 8-OHdG, as
      indicated by LC-MS and immunohistochemical analysis. In addition, ornithine
      decarboxylase (ODC) activity and the number of proliferating cell nuclear antigen
      (PCNA)-positive cells were not altered. An electron paramagnetic resonance spin
      trapping technique showed that TJ-9 scavenges hydroxyl radicals in a dose
      dependent manner. In conclusion, the results of the present study suggest that TJ
      9 prevents hepatocarcinogenesis in association with inhibition of 8-OHdG
      formation.

PMID- 11981763
TI  - Functional and genomic implications of global gene expression profiles in cell
      lines from human hepatocellular cancer.
AB  - Global gene expression profiles in cancer have impacted both classification of
      tumors and definition of molecular pathways in neoplasia. To explore the
      possibility of employing human tumor cell lines to obtain information on the
      functional genomics of the early stages of tumorigenesis, we have characterized
      variation in gene-expression patterns in a cytogenetically well-defined series of
      cell lines derived from human hepatocellular carcinoma (HCC). Microarrays
      containing 6,720 sequence-verified human cDNAs were used in this study. Nineteen
      well-characterized HCC cell lines were analyzed, and a nontumorigenic liver
      derived epithelial cell line (Chang) was used as a reference. Each sample was
      examined at least twice by switching fluorescent dyes, Cy-5 and Cy-3, and average
      values of 2 experiments on each sample were used for further analysis. Analysis
      of the clustered data revealed 2 distinctive subtypes of gene-expression patterns
      among the 19 cell lines, suggesting a degree of heterogeneity among the gene
      expression profiles of cell lines. Remarkably, expression of alpha-fetoprotein
      (AFP) was highly correlated with the molecular subtypes of HCC. Although the 3
      most distinctive gene-expression modules represented the signatures of 2
      different subgroups of HCC, most of the cell lines shared many coexpressed genes.
      However, sets of coexpressed genes that are specific for the subtypes of HCC were
      identified. Furthermore, our results indicate that the comparison between gene
      expression patterns and structural alterations in chromosomes is potentially
      useful in identifying genes critical in early stages of tumorigenesis. In
      conclusion, these results not only identified unrecognized subtypes of HCC, but
      also provided potential molecular markers for each subtype that can be useful for
      diagnostic and/or therapeutic purposes.

PMID- 11981764
TI  - Naked DNA injection for liver metastases treatment in rats.
AB  - The cytosine deaminase (CD) gene converts the nontoxic prodrug, 5-fluorocytosine
      (5-FC), into 5-fluorouracil (5-FU). We previously showed that injection of CD
      bearing cancer cells followed by 5-FC treatment can act as an autologous tumor
      vaccine in a syngenic liver metastasis model in rats. In the present work, we
      analyzed the antitumor efficiency of a direct intratumoral injection of a CD
      expressing plasmid. In rats bearing microscopic or macroscopic metastases in
      right and left liver lobes, an injection of a CD-expressing plasmid was performed
      in the left lobe tumor, followed by 5-FC treatment of the animals. A significant
      regression of the DNA-injected tumor was observed in 5-FC-treated rats, both in
      microscopic (P =.007) or advanced (P <.0001) tumor models. Moreover, this
      treatment also induced a potent distant bystander effect on untreated
      controlateral liver tumors and extrahepatic metastases, resulting in an increased
      survival compared with control animals in both tumor models (P <.05). In
      conclusion, these data suggest that direct intratumoral injection of a CD
      expressing plasmid, associated to 5-FC administration, can constitute a powerful
      and innocuous alternative treatment for unresectable liver metastases from colon
      carcinoma.

PMID- 11981765
TI  - M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan.
AB  - Mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) tumor
      suppressor- gene mutation is an early event in human hepatocellular carcinoma
      (HCC) formation in the United States, but its role in hepatocarcinogenesis in
      Japan is unclear. We therefore determined M6P/IGF2R mutation frequency in HCCs
      from patients who resided in the southern, central, and northern regions of
      Japan. Ten single nucleotide polymorphisms were used to identify HCCs and
      dysplastic liver nodules with M6P/IGF2R loss of heterozygosity. The retained
      allele in these tumors was also assessed for point mutations and deletions in the
      M6P/IGF2R ligand binding domains by direct sequencing of polymerase chain
      reaction (PCR) amplified DNA products. Fifty-eight percent (54 of 93) of the
      patients were heterozygous at the M6P/IGF2R locus, and 67% (43 of 64) of the HCCs
      and 75% (3 of 4) of the dysplastic nodules had loss of heterozygosity. The
      remaining allele in 21% of the HCCs contained either M6P/IGF2R missense mutations
      or deletions, whereas such mutations were not found in the dysplastic lesions. In
      conclusion, M6P/IGF2R is mutated in HCCs from throughout Japan with a frequency
      similar to that in the United States. Loss of heterozygosity in dysplastic liver
      nodules provides additional evidence that M6P/IGF2R haploid insufficiency is an
      early event in human hepatocarcinogenesis.

PMID- 11981766
TI  - Randomized controlled trial of transarterial lipiodol chemoembolization for
      unresectable hepatocellular carcinoma.
AB  - This randomized, controlled trial assessed the efficacy of transarterial Lipiodol
      (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France)
      chemoembolization in patients with unresectable hepatocellular carcinoma. From
      March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed
      unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly
      were assigned to treatment with chemoembolization using a variable dose of an
      emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through
      the hepatic artery (chemoembolization group, 40 patients) or symptomatic
      treatment (control group, 40 patients). One patient assigned to the control group
      secondarily was excluded because of unrecognized systemic metastasis.
      Chemoembolization was repeated every 2 to 3 months unless there was evidence of
      contraindications or progressive disease. Survival was the main end point. The
      chemoembolization group received a total of 192 courses of chemoembolization with
      a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in
      a marked tumor response, and the actuarial survival was significantly better in
      the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the
      control group (1 year, 32%; 2 years, 11%; 3 years, 3%; P =.002). When adjustments
      for baseline variables that were prognostic on univariate analysis were made with
      a multivariate Cox model, the survival benefit of chemoembolization remained
      significant (relative risk of death, 0.49; 95% CI, 0.29-0.81; P =.006). Although
      death from liver failure was more frequent in patients who received
      chemoembolization, the liver functions of the survivors were not significantly
      different. In conclusion, in Asian patients with unresectable hepatocellular
      carcinoma, transarterial Lipiodol chemoembolization significantly improves
      survival and is an effective form of treatment.

PMID- 11981767
TI  - Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis.
AB  - The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary
      cirrhosis (PBC) is not well known. The aims of this study are to determine HCC
      incidence and survival, and to identify risk factors associated with these
      outcomes in patients with PBC. We collected information on 396 patients with PBC
      at enrollment and followed-up from 6 to 271 months. They were all negative for
      hepatitis B and C virus markers. HCC was detected by scanning with
      ultrasonography, computed tomography, or both every 4 to 6 months. Life
      expectancy (LE) was approximated with the declining exponential approximation of
      LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC
      in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly
      higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by
      the tenth year, respectively. P =.021). Proportional hazards analysis showed 3
      factors are independently associated with the development of HCC: age at the time
      of diagnosis, male gender, and history of blood transfusion. Age, male gender,
      and advanced-stage PBC were associated with survival, but HCC development was
      not. The disease-specific annual mortality rate was estimated to be 0.008 for
      women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in
      old patients with advanced-stage PBC, but HCC does not affect the patients'
      survival.

PMID- 11981768
TI  - Pretransplant renal function predicts survival in patients undergoing orthotopic
      liver transplantation.
AB  - The objective of this study was to determine the impact of pretransplant renal
      function on graft and patient survival rates after orthotopic liver
      transplantation (OLT) using the United Network for Organ Sharing (UNOS) database
      for adults who underwent OLT between 1988 and 1996. Based on calculated
      creatinine clearance (CCr) at the time of OLT, patients were classified
      arbitrarily into those with normal renal function (>70 mL/min) and mild (40-69.9
      mL/min), moderate (20-39.9 mL/min), and severe (<20 mL/min) renal insufficiency.
      Of the 20,281 patients who underwent transplantation, complete data were
      available for 19,261 patients. Of these, 12,778 (67%) had normal CCr (mean, 118
      +/- 50 mL/min) and 4,419 (22%) had mild (56 +/- 8.5 mL/min), 1,560 (8%) had
      moderate (30 +/- 5.7 mL/min), and 504 (3%) had severe (14 +/- 3.6 mL/min) renal
      failure. UNOS status 1 was more common in patients with moderate and severe renal
      failure. Primary graft nonfunction and 30-day mortality rates were higher and 1-,
      2-, and 5-year graft and patient survival rates were lower in patients with
      moderate or severe renal failure. Multiple regression analysis showed that renal
      failure was an independent predictor of 30-day and 2-year mortality after
      adjusting for the recipient's age, sex, etiology of liver disease, diabetes
      status, body mass index, cold ischemic time, and UNOS status. CCr less than 40
      mL/min was associated with significantly lower short-term and long-term graft and
      patient survival rates. In conclusion, our findings suggest that when Mayo End
      Stage Liver Disease (MELD) score is used to prioritize organ allocation, lower
      than-expected graft and patient survival rates may be seen.

PMID- 11981769
TI  - Bilirubin induces apoptosis via the mitochondrial pathway in developing rat brain
      neurons.
AB  - Increased levels of unconjugated bilirubin, the end-product of heme catabolism,
      are detrimental to the central nervous system. To examine the role of apoptosis
      in bilirubin-induced toxicity and to characterize the biochemical pathway of cell
      death, we exposed developing rat brain neurons to purified unconjugated bilirubin
      at concentrations below and above saturation of human serum albumin. Isolated
      neurons treated with bilirubin showed increased levels of apoptosis.
      Mitochondrial cytochrome c was extensively released and accumulated in cytosol.
      Consistent with this observation, caspase-3 was activated and the full-length
      substrate poly(ADP)ribose polymerase (PARP) degraded, even in the presence of
      very modestly elevated concentrations of bilirubin. In parallel, all events were
      prevented in cells preincubated with ursodeoxycholate. Further experiments showed
      that bilirubin diminished mitochondrial transmembrane potential (DeltaPsi(m)) and
      increased mitochondrial-associated Bax protein levels, while directly disrupting
      membrane lipid and protein structure. In conclusion, bilirubin induces
      mitochondrial depolarization and Bax translocation via physical interaction with
      membranes, mediating the mitochondrial pathway of apoptosis in neurons exposed to
      bilirubin. These results provide a novel insight into the mechanism of bilirubin
      induced toxicity.

PMID- 11981770
TI  - Relationship between acetaldehyde levels and cell survival in ethanol
      metabolizing hepatoma cells.
AB  - We have created a number of recombinant Hep G2 cell lines, designated VA cells,
      that constitutively express alcohol dehydrogenase. Oxidation of ethanol by the VA
      cells results in the production and accumulation of acetaldehyde, and a dramatic
      increase in the nicotinamide adenine dinucleotide, reduced (NADH)/nicotinamide
      adenine dinucleotide (NAD(+)) ratio (redox-state). It is believed that production
      of acetaldehyde, and the increase in the redox-state of hepatocytes, are
      responsible for many of the dysfunctions associated with alcoholic liver disease.
      When the VA cells were cultured in the presence of ethanol, we observed a
      dramatic reduction in cell accumulation. This reduction was more pronounced in
      cells that metabolized ethanol more efficiently. Inhibition of alcohol
      dehydrogenase activity abolished this reduction, demonstrating that ethanol
      oxidation was required for this dysfunction. Subsequent investigations indicated
      that this ethanol oxidation-mediated reduction in cell accumulation was the
      result of both cytotoxicity and impaired DNA synthesis. To dissociate the
      increase in the cellular redox-state from acetaldehyde production, VA cells were
      cultured in the presence of isopropanol. The oxidation of isopropanol results in
      similar redox changes, but the metabolic by-product of isopropanol oxidation is
      acetone. The metabolism of isopropanol by VA cells resulted in very little
      reduction in cell number. Furthermore, treatment of ethanol-metabolizing VA cells
      with the aldehyde dehydrogenase inhibitor, cyanamide, increased the levels of
      acetaldehyde and resulted in an additional reduction in cell number. In
      conclusion, these studies indicated that exposure to acetaldehyde caused
      cytotoxicity, as well as the ethanol oxidation-mediated reduction in cell number.

PMID- 11981771
TI  - Mitochondrial oxidative stress and CD95 ligand: a dual mechanism for hepatocyte
      apoptosis in chronic alcoholism.
AB  - Apoptosis plays an important role in the progression of alcohol-induced liver
      disease to cirrhosis. Oxidative stress is an early event in the development of
      apoptosis. The major aim of this study was to study the conditions in which
      oxidative stress occurs in chronic alcoholism and its relationship with apoptosis
      of hepatocytes. We have found that oxidative stress is associated with chronic
      ethanol consumption in humans and in rats, in the former independently of the
      existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces
      apoptosis in hepatocytes isolated from alcoholic rats, but not in those from
      control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome P450
      2E1, prevents ethanol-induced cell death. Ethanol-induced apoptosis is caused by
      increased reactive oxygen species (ROS) driven by increased availability of the
      reduced form of nicotinamide-adenine dinucleotide (NADH) owing to mitochondrial
      acetaldehyde metabolism and it is prevented by blocking the opening of
      mitochondrial permeability transition (MPT) pores with cyclosporine A. Inhibition
      of nitric oxide (NO) synthase or addition of antioxidant vitamins C and E
      completely prevented ethanol-induced apoptosis. Mitochondrial oxidative stress,
      which occurs during chronic alcoholism, renders hepatocytes susceptible to
      apoptosis. On the other hand, the CD95 ligand expression was up-regulated by
      acetaldehyde. In conclusion, ethanol induces apoptosis via 2 different pathways:
      MPT and up-regulation of the expression of CD95-Fas ligand. The overproduction of
      ROS by mitochondria, driven by acetaldehyde metabolism, is a common trigger of
      both mechanisms.

PMID- 11981772
TI  - Characterization of two hepatitis B virus populations isolated from a hepatitis B
      surface antigen-negative patient.
AB  - In a study of surface antigen-negative, but weakly hepatitis B virus (HBV) DNA
      positive, patients, we were able to amplify and clone whole HBV genomes from the
      serum of a cirrhotic patient. Sequencing showed that the patient harbored two
      different HBV populations, one of genotype A and the other of genotype D, with
      the genotype D genome apparently predominating. The surface antigen of the
      genotype A virus is heavily mutated, especially in the extracellular <<
      determinant a >> region, with several mutations that have not been previously
      described. The genotype D virus is a precore mutant. Both genomes possess the
      common A1762T-G1764A double mutation of the basal core promoter (BCP), and the
      genotype D virus is also mutated in the << TATA box >> of the large surface
      antigen promoter. Biological characterization showed that the genotype A genome
      was fully replication-competent, whereas the genotype D genome replicated poorly.
      The small surface antigen of the genotype A virus was only very weakly recognized
      by commercial tests. The small surface antigen of the genotype D virus could be
      recognized by the tests, but it was mainly retained within transfected cells,
      probably because of an excess of large surface antigen. In conclusion, the
      cryptic nature of this double HBV infection is characterized by the predominance
      of the replication-deficient genotype D virus over the replication-competent
      genotype A virus.

PMID- 11981773
TI  - Intrahepatic and circulating HLA class II-restricted, hepatitis C virus-specific
      T cells: functional characterization in patients with chronic hepatitis C.
AB  - To compare the functional features of circulating and intrahepatic hepatitis C
      virus (HCV)-specific CD4+ T cells in chronic HCV infection, peripheral blood and
      liver-infiltrating lymphocytes from 29 patients with chronic hepatitis C were
      stimulated with structural and nonstructural HCV proteins to produce antigen
      specific T-cell lines and clones. Antigen specificity, fine specificity,
      phenotype, cytokine production, and T-cell receptor (TCR)-vbeta chain expression
      were analyzed. The results indicate a hierarchy of stimulatory capacity by the
      different HCV proteins, core being the antigen most frequently recognized by CD4+
      intrahepatic lymphocytes, followed by NS4 and NS5. The CD4 response was directed
      simultaneously against different HCV proteins in individual patients, but fine
      specificity analysis indicated that the response was generally focused on a
      limited number of immunodominant epitopes. Although the narrowly focused nature
      of this response may favor the emergence of escape mutations, this event was not
      observed by following-up over time the sequence of 2 epitopes strongly
      immunodominant for intrahepatic CD4 cells of a patient with chronic HCV
      infection. In conclusion, simultaneous analysis of peripheral blood and
      intrahepatic CD4 cells in the same patients indicated a predominant Th1 profile
      of HCV-specific CD4 cells and suggests a specific compartmentalization of virus
      specific T cells into the liver.

PMID- 11981774
TI  - Cellular response to conditional expression of hepatitis C virus core protein in
      Huh7 cultured human hepatoma cells.
AB  - Data suggesting that the hepatitis C virus (HCV) core protein influences normal
      cellular processes remain controversial. To determine the effects of core on
      cellular gene expression in hepatocytes, we developed a human hepatoma (Huh7)
      derived cell line with tightly regulated core expression under the control of a
      tetracycline-regulated promoter. Cells expressing core did not have impaired
      proliferative abilities. Changes in gene expression profiles in response to core
      expression were determined using commercial oligonucleotide microarrays
      (Affymetrix GeneChip). Significant increases were observed in the abundance of
      mRNA-encoding members of the metallothionein (MT) family, as well as nicotinamide
      N-methyltransferase (NNMT) and glutathione peroxidase-like protein (GPLP). These
      changes did not result from removal of tetracycline from growth media, and were
      confirmed in reverse-transcription polymerase chain reaction (RT-PCR) assays.
      They suggest that core protein expression leads to intracellular oxidative
      stress, and that vital cellular functions are, in turn, protected by up
      regulation of cellular antioxidant defense mechanisms. In conclusion, these
      findings can explain many potentially conflicting prior observations concerning
      the effects of core on cellular physiology, and are of relevance to the role of
      core protein in the pathogenesis of HCV-related fibrosis and hepatocellular
      carcinoma.

PMID- 11981775
TI  - Severity and correlates of liver disease in hepatitis C virus-infected injection
      drug users.
AB  - Between May 1996 and June 1998, 210 members of a cohort of 1,667 hepatitis C
      virus (HCV)-infected injection drug users (IDUs) were selected for liver biopsy
      procedure after stratification based on 2 consecutive serum alanine transaminase
      (ALT) levels. Liver histology, which could be fully evaluated for 207 subjects,
      was classified by using the modified Ishak scores. At the time of biopsy, the
      median age of subjects was 41.3 years and the median estimated duration of HCV
      infection was 20.7 years; 94% were African American; 78% men; 31% were human
      immunodeficiency virus (HIV) seropositive; and 76% had HCV genotype 1a or 1b.
      Total modified histologic activity index (MHAI) scores ranged from 0 to 9, and
      26.6% had a total MHAI score of 5 or greater. Persons with a total MHAI score of
      5 or greater were more likely to be HIV infected (P =.04). Higher fibrosis,
      indicated by Ishak modified fibrosis scores of 3 to 6, was present in 10.1% of
      subjects and was found more often in those older than 46 years of age (the
      highest quartile) (P <.01). Both fibrosis scores of 3 or greater and total scores
      of 5 or greater were associated with elevated ALT, aspartate transaminase (AST),
      and gamma-glutamyl transpeptidase (GGT) levels (P <.01). When serial values were
      considered, the results of liver enzyme testing could reduce the probability of
      an IDU having a fibrosis score of 3 or greater from 10% to 3%. In conclusion,
      these data indicate that severe liver disease is uncommon in this urban, HCV
      infected IDU cohort, especially in younger persons and those with repeatedly
      normal liver enzymes.

PMID- 11981776
TI  - The pathobiology of biliary epithelia.
AB  - The morbidity and mortality from chronic biliary diseases (i.e., the
      cholangiopathies) remains substantial. End-stage liver disease from biliary
      causes of cirrhosis (e.g., primary biliary cirrhosis [PBC], and primary
      sclerosing cholangitis) account for approximately one third of patients referred
      for liver transplantation. A single-topic conference sponsored by the American
      Association for the Studies of Liver Diseases entitled "The Pathobiology of
      Biliary Epithelia" brought together investigators to review the status of the
      field of cholangiocyte pathobiology, identify new areas of interest, and propose
      future directions. This information was presented in 6 sessions: "Structural and
      Functional Characteristics of the Bile Duct System," "Biological Topics from
      Nonbiliary Epithelia," "Malignant Transformation of Cholangiocytes,"
      "Cholangiocyte Proliferation and Death," "Transport Mechanisms in Bile Duct
      Epithelia," and "Pathobiology of Biliary Epithelia." In the 7 years since the
      first symposium on this topic, major advances have been made in our understanding
      of ductal bile formation, including, greater insight into the hormones,
      intracellular signaling mechanisms, and effector proteins responsible for bile
      secretion and absorption. More sophisticated imaging technologies have increased
      our understanding of the polarity of cholangiocytes, their embryology and
      ultrastructural anatomy, and in vivo human secretory responses to current medical
      therapy. Information on mediators of inflammation permeated many sessions, having
      potentially important roles in malignant transformation of cholangiocytes,
      cholangiocyte apoptosis, fluid and electrolyte transport, and have begun to be
      specifically characterized for certain biliary diseases, e.g., acquired
      immunodeficiency syndrome (AIDS) cholangiopathy and graft-versus-host disease
      (GVHD).

PMID- 11981777
TI  - Is "Gilbert's" the culprit in indinavir-induced hyperbilirubinemia?

PMID- 11981778
TI  - Is cerebral edema a component of the syndrome of hepatic encephalopathy?

PMID- 11981779
TI  - Clinical significance of hepatitis B virus genotypes.

PMID- 11981780
TI  - Mechanisms of bilirubin neurotoxicity.

PMID- 11981781
TI  - Treatment of ribavirin/interferon-induced anemia with erythropoietin in patients
      with hepatitis C.

PMID- 11981782
TI  - Model for end-stage liver disease (MELD) for predicting mortality in patients
      with acute variceal bleeding.

PMID- 11981783
TI  - The SJL/J mouse is not a model for PBC.

PMID- 11981784
TI  - By indirections find directions out.

PMID- 11981785
TI  - Techniques for performing multidetector-row computed tomographic angiography.
AB  - The introduction of multidetector-row computed tomography (CT) scanners has
      substantially improved the quality and ease of performing CT angiography. CT
      angiography is a robust method of volumetric vascular imaging that offers
      benefits over conventional angiography. As CT angiography has become a mainstream
      examination in many radiology departments, a discussion of techniques toward
      optimizing CT angiography performed with multidetector-row CT scanners is
      important. Key principles for optimizing spiral CT acquisition are discussed, and
      an explanation of multidetector-row CT principles germane to peripheral vascular
      imaging is presented. A discussion of contrast medium administration strategies
      ensues, with attention toward injection protocol and bolus timing. An overview of
      3-dimensional visualization techniques is subsequently presented, followed by
      some general rules for CT angiographic interpretation. The article concludes with
      anatomically directed protocol considerations for the carotid and intracranial
      circulation, thoracic aorta, pulmonary arteries, abdominal aortoiliac system,
      renal arteries, and lower extremity arterial inflow and run-off.

PMID- 11981786
TI  - Abdominal aortic aneurysms before and after endograft implantation: evaluation by
      computed tomography.
AB  - The evaluation of patients with abdominal aortic aneurysms for endograft
      candidacy and their follow-up after treatment are heavily dependent on radiologic
      imaging. Factors never considered during conventional open repair have become
      crucial to patient selection and procedural success, and the new and developing
      nature of the field of endovascular repair necessitates close surveillance of
      these devices after deployment. Computed tomography (CT) has emerged as the
      single most effective imaging tool for the preprocedural assessment and
      subsequent follow-up of these patients. This article outlines the technical
      parameters for obtaining pre- and postoperative CT examinations in endograft
      patients and discusses the important imaging findings.

PMID- 11981787
TI  - Magnetic resonance angiography: the nuts and bolts.
AB  - Magnetic resonance angiography (MRA) has matured into an extremely reliable and
      valuable diagnostic vascular tool. We are now able to acquire clinically
      diagnostic angiograms in all the major vascular territories by using MRA, thereby
      replacing invasive angiography. This paradigm shift has enormous clinical and
      financial ramifications, as MRA is safer, cheaper, and far more convenient for
      our patients than invasive angiography. Future magnetic resonance imaging
      research developments that are on the verge of being incorporated into clinical
      practice include real-time magnetic resonance fluoroscopy and endovascular
      therapeutic ability. It should therefore be incumbent upon the vascular and
      interventional community to embrace this powerful technology by collaborating and
      integrating with those physicians who possess the skills to perform high-quality
      magnetic resonance imaging. This article provides basic key fundamental concepts
      and protocol guidelines for state-of-the art MRA performance and elucidates
      future directions of this technology as it pertains to the interventional and
      vascular radiologist.

PMID- 11981788
TI  - Gadolinium contrast agents: their role in vascular and nonvascular diagnostic
      angiography and interventions.
AB  - Gadolinium-based contrast agents can be used for diagnostic and interventional
      angiographic procedures to reduce contrast-related nephrotoxicity or in patients
      with a history of severe allergic reaction to iodine-containing contrast
      material. These agents are best used in conjunction with CO(2) to complete
      nondiagnostic CO(2) angiograms and to monitor the progress of a percutaneous
      intervention. However, the total volume of gadolinium that can be administered,
      the reduced quality of gadolinium digital subtraction angiography images, and the
      increased cost of the gadolinium-based agents can limit their use.

PMID- 11981789
TI  - Preventing contrast-induced nephropathy with fenoldopam.
AB  - Fenoldopam is an interesting orphan drug that is a variant of dopamine. It
      differs significantly from dopamine in that it is a specific agonist for the type
      I (DA-1) receptor. The DA-1 receptors are particularly prominent in the renal
      vasculature, renal tubules, mesenteric vasculature, and peripheral vessels. The
      DA-1 receptor stimulation vasodilates renal and peripheral vessels, causing a
      decrease in blood pressure and an increase in renal blood flow (RBF). Stimulation
      of the DA-1 receptors in the tubules causes an increase in sodium excretion,
      which gives rise to an increase in urine volume on the basis of a sodium
      natriuresis. Animal testing with fenoldopam has indicated that it is 6 times more
      potent than dopamine in its ability to decrease renal vascular resistance and
      increase RBF; this suggests that it could be a much more selective and potent
      renal protective agent against any toxin or stimulus that causes renal
      dysfunction by reducing RBF or increasing renal ischemia. The clinical activity
      of fenoldopam, which is administered intravenously, begins almost immediately and
      is clearly noticeable after 5 minutes. The drug has no rebound effect, and its
      use can be stopped at any time. The protocol for the use of fenoldopam as a renal
      protective agent (performed at the University of Minnesota) involves starting an
      intravenous fenoldopam infusion 2 hours before the procedure at a rate of 0.1
      microg/kg/min and increasing the dose in increments of 0.1 microg/kg/min every 20
      minutes, until a rate of 0.5 microg/kg/min is reached or the systolic blood
      pressure falls more than 40 mm Hg (or below 110 mm Hg). Any infusion level at or
      above 0.1 microg/kg/min is considered acceptable because the response in
      individual patients varies so widely. The fenoldopam infusion is maintained at
      the maximum rate throughout the procedure and for up to 4 hours after the end of
      the contrast administration. At the University of Minnesota, we have had
      anecdotal experience using the drug in 29 patients. The drug was used for
      patients who were thought to be at the highest risk for contrast-induced
      nephropathy, ie, patients who have both diabetes and pre-existing renal failure.
      In this small group of patients in whom hydration and other variables were not
      controlled, there was a startling lack of contrast-induced creatinine increase at
      any point during the 24 to 48 hours after the administration of contrast in all
      but 1 patient. Our experience suggests that fenoldopam may be of distinct benefit
      to high-risk patients who need intravascular contrast, especially those who may
      receive a large contrast dose, such as patients undergoing peripheral or coronary
      angiography and intervention and/or computed tomography. Although it is
      impossible on the basis of simple anecdotal case reports to determine whether or
      not the drug was the primary reason that such a marked protective effect was
      seen, the results are promising enough to indicate that a careful, prospective,
      randomized trial of fenoldopam versus hydration is warranted.

PMID- 11981790
TI  - Carbon dioxide digital subtraction angiography: the practical approach.
AB  - CO(2) has developed into a viable alternative to iodinated contrast for digital
      vascular imaging. Because CO(2) is a gas, it has a unique set of properties that
      affords certain advantages over iodinated contrast in a variety of settings.
      However, if CO(2) is used inappropriately, these same properties are associated
      with a unique set of rare but potentially harmful events. Therefore, it is
      essential that these unique characteristics be understood in order to employ a
      few simple precautionary measures. Fortunately, there is a delivery system
      currently available that is readily assembled and easy to use that ensures the
      appropriate administration of CO(2). This system, combined with experience, can
      reduce the greater labor intensity sometimes associated with CO(2) digital
      subtraction angiography. When it is used appropriately, CO(2) digital subtraction
      angiography alone or in combination with iodinated contrast offers diagnostic and
      interventional rewards that are not available with traditional intravascular
      contrast examinations.

PMID- 11981791
TI  - Intravascular ultrasound.
AB  - Intravascular ultrasound imaging, in which a catheter-based miniature sonographic
      transducer is introduced into vessels, provides high-resolution, cross-sectional,
      real-time imaging of the vessel wall and lumen. It has been found to be useful as
      both a diagnostic and therapeutic adjunct in the evaluation and management of
      various arterial and venous disorders. Used in conjunction with other imaging
      modalities, such as conventional angiography, spiral computed tomography, and
      magnetic resonance angiography, it has the potential to increase the accuracy of
      percutaneous interventions and device sizing.

PMID- 11981792
TI  - Angioscopy.
AB  - Angioscopy provides a magnified, real-time, 360-degree view of the endoluminal
      surface of blood vessels, yielding unique information that is often complementary
      to conventional angiography. This unique perspective can significantly enhance
      one's perception and appreciation of endovascular disease. Although angioscopy is
      primarily used as a research tool, its ability to characterize accurately the
      morphology and color of atherosclerotic lesions may lead to improved treatment
      and better clinical outcomes.

PMID- 11981793
TI  - Basic arterial techniques for peripheral arterial thrombolysis.
AB  - This article is an overview of the techniques of percutaneous intervention for
      recanalizing acute or subacute occluded arteries. The indications and results for
      specific thrombolytics and interventions are discussed in subsequent articles.

PMID- 11981794
TI  - Bleeding complications associated with the use of rt-PA versus r-PA for
      peripheral arterial and venous thromboembolic occlusions.
AB  - This article analyzes the early experience with alteplase (rt-PA) and reteplase
      (r-PA) to identify noteworthy differences in bleeding and to determine
      correlations with dosage, concomitant anticoagulation, and duration of infusion.
      A retrospective review of the medical records was unavailable for the initial 82
      patients who were treated with either rt-PA (44) or r-PA (38) for peripheral
      arterial or venous occlusions after urokinase therapy. Successful recanalization
      was achieved in 31/44 (70%) of the patients treated with rt-PA and in 34/38 (89%)
      of the patients treated with r-PA. Significant bleeding was documented in 20/44
      (45%) of the rt-PA-treated patients (including 14 transfusions) versus 3/38 (8%)
      of the r-PA-treated patients (3 transfusions). Concomitant anticoagulation with
      either preceding warfarin (international normalized ratio > 1.1) or a bolus of
      heparin at the outset of the infusion was associated with significant bleeding in
      13/17 (76%) of the rt-PA-treated patients (including 9 transfusions) versus 0/17
      in the r-PA-treated patients. No significant correlation between either mean dose
      or total dose and bleeding was shown for either drug. Early experience indicates
      that r-PA is at least as effective as rt-PA for the thrombolysis of peripheral
      arterial and venous occlusions. It also appears that r-PA is less likely than rt
      PA to be associated with significant bleeding during such infusions, especially
      if the patient is concomitantly anticoagulated.

PMID- 11981795
TI  - Alteplase and tenecteplase: applications in the peripheral circulation.
AB  - Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator,
      became the first genetically engineered thrombolytic approved by the Food and
      Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to
      AMI, alteplase is currently approved for the treatment of acute ischemic stroke
      and pulmonary embolism, and we anticipate approval for catheter clearance in late
      2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney
      cell-derived urokinase, alteplase has become an alternative agent in peripheral
      vascular applications. Because few interventionalists had prior experience with
      the handling and dosage of alteplase, the Advisory Panel to the Society of
      Cardiovascular and Interventional Radiology established practice guidelines for
      use in noncoronary applications. Emerging clinical experience with contemporary
      dosing regimens shows a safety and efficacy profile similar to urokinase but with
      significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified
      version of alteplase. TNK is the only plasminogen activator available that has
      shown a significantly enhanced safety profile versus alteplase in AMI. Approved
      for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life,
      increased resistance to plasminogen activator inhibitor, and improved fibrin
      specificity compared with alteplase. Because of its enhanced safety profile, TNK
      may be a desirable agent for peripheral vascular applications. Initial clinical
      studies with TNK in acute arterial and venous disease are ongoing. This article
      outlines the Advisory Panel guidelines for using alteplase and highlights
      features of tenecteplase.

PMID- 11981796
TI  - The use of glycoprotein IIb/IIIa antagonists in peripheral arterial occlusion.
AB  - The use of intra-arterial, catheter-directed thrombolytic therapy has been
      associated with the necessity to infuse the agents over a protracted period of
      time. The large, randomized studies suggest that most treatments require more
      than 24 hours of infusion. There are data to suggest that the risk of
      complications, especially hemorrhagic complications, increases as the duration of
      administration increases. Moreover, the economic burden of thrombolytic therapy
      increases in proportion to the length of infusion, specifically with respect to
      the cost of the agent and the use of hospital resources, such as the intensive
      care unit. For these reasons, it is desirable to formulate a treatment strategy
      that results in a more rapid rate of thrombolysis. Thrombolytic dissolution of an
      occluding thrombus is a dynamic process; new thrombus is laid down as old
      thrombus is dissolved. Because this process occurs in the high-flow arterial
      milieu, platelets are of prime importance and contribute directly to the
      phenomenon of rethrombosis. Platelets have also been implicated in the more
      chronic problems associated with smooth muscle cell and leukocyte-dependent
      intimal hyperplasia that culminates in restenosis at sites of arterial injury.
      Platelet antagonists, such as the glycoprotein IIb/IIIa inhibitors, are
      attractive as adjuvants to peripheral thrombolysis; the rate of thrombolysis may
      be increased by inhibiting new thrombus deposition. The agents may also
      discourage the formation of a restenotic lesion at the site of intervention.
      Initial studies suggest that this may indeed be the case, and there is much
      interest in validating the use of platelet antagonists through the performance of
      well-designed clinical trials.

PMID- 11981797
TI  - Catheter-directed thrombolysis for lower extremity deep vein thrombosis.
AB  - The elimination of the embolic potential of existing thrombus, the restoration of
      unobstructed flow, the prevention of further thrombosis, and the preservation of
      venous valve function are the ideal goals of therapy for acute deep vein
      thrombosis (DVT). Meeting these goals will not only prevent pulmonary embolism
      but will also minimize the long-term sequelae of venous hypertension and the
      development of postthrombotic syndrome (PTS). Treatment strategies aimed at
      eliminating or reducing the risk of PTS should focus on preserving valvular
      function and eliminating the risk of continued venous obstruction after acute
      DVT. Thrombolytic agents are an attractive form of early therapy because they
      have the ability to eliminate obstructive thrombus in the deep veins and should
      therefore help provide protection against PTS. The perceived benefits of early
      and rapid recanalization in preserving valve function has been the basis for the
      use of lytic therapy to treat acute DVT.

PMID- 11981798
TI  - Thrombolytic therapy for acute ischemic stroke.

PMID- 11981799
TI  - Contemporary treatment of thrombosed hemodialysis grafts.
AB  - Maintaining hemodialysis grafts remains a difficult problem. Before the early
      1990s, graft declotting was usually performed in the surgical suite. Percutaneous
      declotting has been evolving since the mid-1980s. Initially, a low-dose
      thrombolytic infusion of streptokinase through a single catheter was used.
      Crossing catheters with a higher-dose infusion of urokinase was then introduced.
      This technique was modified with the adjunctive use of pharmacomechanical
      techniques with the use of compliant balloons and the adjunctive use of heparin.
      The advent of the "lyse-and-wait" technique provided a simpler and quicker way to
      declot thrombosed grafts by using urokinase, with similar outcomes. Since the
      removal of urokinase from the market, multiple mechanical devices have been used
      with similar success. Recent reports concerning the use of newer-generation
      thrombolytic agents report similar outcomes, with a reduction in total cost.

PMID- 11981800
TI  - Techniques in dosing for thrombolysis of occluded central venous catheters.
AB  - Dosing of thrombolytic agents for restoration of flow to thrombotically occluded
      central venous catheters has been empiric. The lowest effective dose of any agent
      is not known. Given that none of the dosing regimens in current use has ever been
      found to be toxic, this is probably not a major clinical problem as long as the
      regimen is highly effective. Thrombolytic regimens differ in the type of drug,
      dose of drug, method of administration (injection versus prolonged infusion), and
      duration of administration. All of these variables are important in determining
      the efficacy, and possibly the toxicity, of a regimen. Active research is being
      conducted to determine the most effective ways of using the expanding number of
      thrombolytic medications that are now, or soon may be, on the market.

PMID- 11981801
TI  - Embryogenesis of the glowworm Rhagophthalmus ohbai Wittmer (Insecta: Coleoptera,
      Rhagophthalmidae), with emphasis on the germ rudiment formation.
AB  - The early embryonic development and features of the developing embryo of the
      glowworm Rhagophthalmus ohbai are described chiefly by light microscopy, with
      emphasis on the germ rudiment formation and its phylogenetic implication. The egg
      period is 30-34 days at about 23 degrees C. The newly laid egg is a short
      ellipsoid, 1.09 by 0.78 mm in size, and the size increases to 1.15 by 0.95 mm by
      17 days after oviposition. Cleavage is of the typical superficial type. The germ
      disk is formed by cell aggregation of the embryonic area at the anterior end of
      the egg. The central part of the germ disk then sinks into the yolk and the
      spherical germ rudiment is formed by fusion of the amnioserosal folds extended
      from all margins of the germ disk. The inner region of the germ rudiment soon
      becomes slender and develops into the short embryo, whereas the outer region
      facing the anterior end is extended to form the thin amnion. The embryo then
      rapidly elongates, the elongation being accompanied by embryo segmentation and
      formation of appendages. The submerged condition of the embryo persists until
      about 17 days after oviposition (about 1 day before embryonic revolution) and
      thereafter the embryo becomes superficial in position. The presence of the
      following embryonic characters in R. ohbai supports the molecular data placing it
      within the Lampyridae: 1) formation of a spherical germ rudiment near the
      anterior end of the egg, and 2) the submerged condition of the developing embryo
      persists until shortly before revolution.

PMID- 11981802
TI  - Functional morphology of the forelimb of tupaiids (Mammalia, Scandentia) and its
      phylogenetic implications.
AB  - In this study, the forelimb of 12 species of tupaiids was analyzed functionally
      and compared to that of other archontan mammals. Several differences that relate
      to differential substrate use were found in the forelimb morphology of tupaiids.
      These differences included shape of the scapula, length and orientation of the
      coracoid process, size of the lesser tuberosity, shape of the capitulum, length
      of the olecranon process, and shape of the radial head and central fossa. The
      forelimb of the arboreal Ptilocercus lowii, the only ptilocercine, is better
      adapted for arboreal locomotion, while that of tupaiines is better adapted for
      terrestrial (or scansorial) locomotion. While the forelimb of the arboreal
      Ptilocercus appears to be habitually flexed and exhibits more mobility in its
      joints, a necessity for movement on uneven, discontinuous arboreal supports, all
      tupaiines are characterized by more extended forelimbs and less mobility in their
      joints. These restricted joints limit movements more to the parasagittal plane,
      which increases the efficiency of locomotion on a more even and continuous
      surface like the ground. Even the most arboreal tupaiines remain similar to their
      terrestrial relatives in their forelimb morphology, which probably reflects the
      terrestrial ancestry of Tupaiinae (but not Tupaiidae). The forelimb of Urogale
      everetti is unique among tupaiines in that it exhibits adaptations for scratch
      digging. Several features of the tupaiid forelimb reflect the arboreal ancestry
      of Tupaiidae and it is proposed that the ancestral tupaiid was arboreal like
      Ptilocercus. Also, compared to the forelimb character states of tupaiines, those
      of Ptilocercus are more similar to those of other archontans and it is proposed
      that the attributes of the forelimb of Ptilocercus are primitive for the
      Tupaiidae. Hence, Ptilocercus should be considered in any phylogenetic analysis
      that includes Scandentia.

PMID- 11981803
TI  - Skull osteology of Parvilacerta parva, a small-sized lacertid lizard from Asia
      Minor.
AB  - The skull of the poorly known Asia Minor lacertid lizard Parvilacerta parva is
      described. In comparison to other palaearctic lacertids, Parvilacerta parva
      displays several peculiar traits such as a large braincase, a short parietal
      table, closed post-temporal openings, reduced ossification, or a large lacrimal.
      Many features are related to the small size of Parvilacerta parva and are of
      apparently heterochronic nature, as they can also be found in certain ontogenetic
      stages of other lacertid species. Small size and heterochrony even seem to be
      factors involved in the less-developed sexual dimorphism of Parvilacerta parva.
      The described morphology is interpreted to be related to a life history strategy
      in r-selecting, semiarid environments.

PMID- 11981804
TI  - Vascularization of the brains of the Atlantic and Pacific hagfishes, Myxine
      glutinosa and Eptatretus stouti: a scanning electron microscope study of vascular
      corrosion casts.
AB  - The microvascularization of the brains of the hagfishes, Myxine glutinosa L. and
      Eptatretus stouti, were studied by scanning electron microscopy (SEM) of
      microvascular corrosion casts. Sections of these casts were used to determine the
      vascular territories of defined brain areas. Histological serial sections (10
      microm) of the brains served for correlation of findings. Analysis of the
      microvascular casts of both species revealed that the blood supply to and from
      these brains arose ventrally and dorsally, respectively. Neither species
      possesses an arterial circle (Circulus Willisi) and both have similar
      microvascular patterns. The only difference between Myxine and Eptatretus was
      that the posterior cerebral artery in Myxine divides into mesencephalic and
      rhombencephalic branches, and in Eptatretus a third branch, termed telencephalic
      branch, arises from the posterior cerebral artery. 3D-morphometry revealed that
      luminal diameters of: 1) intracerebral arteries and arterioles range from 35.11
      +/- 5.66 microm (mean +/- SEM) in the hypothalamus to 92.69 +/- 14.48 microm in
      the thalamus; 2) capillaries range from 17.8 +/- 0.44 microm in the olfactory
      bulb to 21.70 +/- 0.87 microm in the basal ganglia; and 3) intracerebral venules
      and veins range from 49.38 +/- 4.17 microm in the hypothalamus to 75.58 +/- 6.59
      microm in the rhombencephalon. Interbranching distances of arteries and
      arterioles range from 179.19 +/- 11.32 microm in the optic tectum to 235.19 +/-
      94.64 microm in the hypothalamus. Capillaries range from 91.07 +/- 6.22 microm in
      the hypothalamus to 116.15 +/- 9.45 microm in the thalamus, and venules and veins
      range from 137.30 +/- 18.11 microm in the hypothalamus to 189.83 +/- 17.47 microm
      in the optic tectum. Intervascular distances range from 70.58 +/- 3.58 microm in
      the olfactory bulb to 89.52 +/- 5.74 microm in the optic tectum. Branching angles
      of arteries and arterioles range from 38.39 +/- 10.9 degrees in the olfactory
      bulb to 100.73 +/- 9.4 degrees in the optic tectum, and the branching angles of
      capillaries range from 74.40 +/- 5.42 degrees in the optic tectum to 90.24 +/-
      4.66 degrees in the olfactory bulb. Finally, the branching angles of the venules
      and veins range from 67.84 +/- 6.83 degrees in the tegmentum of the mesencephalon
      to 92.30 +/- 6.35 degrees in the optic tectum.

PMID- 11981805
TI  - Morphological changes in the efferent ducts during the main phases of the
      reproductive cycle of birds.
AB  - The changes that take place in the efferent ducts during the major phases of the
      reproductive cycle of birds were studied morphologically using standard
      histological, morphometric, and ultrastructural methods in prepuberal, sexually
      mature and sexually active, and sexually mature but sexually inactive domestic
      fowl (Gallus domesticus), drake (Anas platyrhynchos), and guinea fowl (Numida
      meleagris). Profound structural and dimensional changes occurred in both segments
      (proximal and distal) of the efferent ducts and, in particular, in the
      nonciliated (Type I) cell of the proximal duct of sexually mature but inactive
      birds. The subapical tubulovacuolar system was markedly atrophic in nonciliated
      (Types I and II) cells and the numerous round dense globules of Type I cells that
      normally occurred in sexually active birds were replaced by fewer and more
      pleomorphic bodies containing lipofuscin granules in sexually resting birds.
      Lipid droplets, few and extremely large in inactive drakes but numerous and
      smaller in size in guinea fowls and domestic fowls, occurred in the Type I cell
      at both infra- and supranuclear levels of resting but not in prepuberal or
      sexually active birds. Ciliated cells in both segments of the ducts exhibited
      fewer and less profound phase-dependent changes ultrastructurally. Generally, the
      Type I cells of the proximal efferent duct appeared to be more sensitive to
      androgen deprivation than the Type II cell of the distal efferent duct or
      ciliated cells in both ducts. These morphologically phase-dependent features of
      the efferent ducts of birds may be used, together with or independent of
      testicular changes, in the determination of the status of the testis and
      epididymis of a male bird with regard to the reproductive cycle, especially in
      seasonally breeding species.

PMID- 11981806
TI  - Functional-adaptive analysis of the hindlimb anatomy of extant marsupials and the
      paleobiology of the Paleocene marsupials Mayulestes ferox and Pucadelphys
      andinus.
AB  - This article analyzes the adaptations of the hindlimb of two Early Paleocene
      marsupials, Mayulestes ferox and Pucadelphys andinus. This analysis is based on
      detailed comparisons with various extant marsupials, both South American and
      Australian. In the case of the South American opossums, original myological data
      were collected and osteological-myological associations were related to their
      locomotor behavior. The use of Australian genera helped to improve the appraisal
      of the locomotory habits of the fossil taxa. Several features are indicative of
      the ability of Mayulestes to climb or walk on uneven surfaces (e.g., very mobile
      hip joint, astragalocalcaneal joint pattern), and some other features emphasize a
      relative agility (e.g., strongly everted iliac blades, morphology of the distal
      epiphysis of the femur, medially stabilized cruroastragalar joint). Pucadelphys
      exhibits a hindlimb relatively similar morphologically to that of Mayulestes, but
      with features indicating slightly increased agility and a terrestrial component
      that is more emphasized than in Mayulestes. The Tiupampa fossils were therefore
      more agile than most living didelphids and resembled the condition observed in
      living dasyurids more. These conclusions complement a previous study performed on
      the forelimb of these fossils.

PMID- 11981807
TI  - Human natural killer cells: their origin, receptors and function.
AB  - The term of "natural killer" (NK) cells was originally assigned on a merely
      functional basis to lymphoid cells capable of lysing certain tumors in the
      absence of prior stimulation. However, both their origin and the molecular
      mechanism(s) involved in their function remained a mystery for many years 1.
      Regarding their origin, clear evidence has now been provided both in mouse and in
      man that NK and T cells may derive from a common precursor 2-5. Thus, mature NK
      cells can be obtained in vitro from CD34(+) cells isolated from umbilical cord
      blood, bone marrow (BM) and even human thymus 6 when cultured in the presence of
      appropriate feeder cells or IL-15. The molecular mechanism allowing NK cells to
      discriminate between normal and tumor cells, predicted by the "missing self
      hypothesis" 7, has been clarified only in recent years. Thus, NK cells recognize
      MHC class I molecules through surface receptors delivering signals that inhibit,
      rather than activate, NK cells. As a consequence, NK cells lyse target cells that
      have lost (or express insufficient amounts of) MHC class I molecules, as
      frequently occurs in tumors and in cells infected by certain viruses.

PMID- 11981808
TI  - Inhibitory oligonucleotides specifically block effects of stimulatory CpG
      oligonucleotides in B cells.
AB  - Reaction to certain motifs in bacterial DNA is an important function of natural
      immunity. For example, single stranded oligonucleotides (ODN) containing the
      motif "not C, unmethylated C, G, not G" are powerful mitogens and apoptosis
      inhibitors for mouse spleen B cells. But replacing GCGTT or ACGTT with GCGGG or
      ACGGG converted a stimulatory 15-mer ODN into an inhibitory ODN. All inhibitory
      ODN had three consecutive G, and a fourth G increased inhibitory activity, but a
      deazaguanosine substitution to prevent planar stacking did not affect activity.
      Inhibitory ODN blocked apoptosis protection and cell-cycle entry induced by
      stimulatory ODN, but not that induced by lipopolysaccharide, anti-CD40 or anti
      IgM+IL-4. ODN-driven up-regulation of cyclin D(2), c-Myc, c-Fos, c-Jun and
      Bcl(XL) and down-regulation of cyclin kinase inhibitor p27(kip1) were all blocked
      by inhibitory ODN. The relative potency of a series of stimulatory and inhibitory
      ODN was the same for all readouts measured. Interference with uptake of
      stimulatory ODN could not account for their inhibitory effects. Even if addition
      of inhibitory ODN was delayed several hours, partial inhibition of stimulatory
      ODN effects occurred. Inhibitory ODN hold potential as antidotes for excessive
      ODN stimulation in the clinical setting and provide an important tool for
      studying ODN recognition.

PMID- 11981809
TI  - Calcineurin Aalpha plays an exclusive role in TCR signaling in mature but not in
      immature T cells.
AB  - Calcineurin has been demonstrated as one of the key enzymes in TCR-mediated
      signaling cascades that lead to the transcription of a variety of cytokines
      including IL-2. In this study, we addressed the role of calcineurin in lymphocyte
      development and peripheral T cell responses using the lymphocytic
      choriomeningitis virus glycoprotein peptide p33-specific, TCR (P14)-transgenic T
      cells that were deficient in calcineurin subunit A alpha-isoform (CNAalpha(-/-)).
      Fetal thymic organ culture of P14/CNAalpha(-/-) lobes showed no defect in
      positive or negative selection of thymocytes. In addition, peptide-induced
      peripheral T cell deletion was also normal in CNAalpha-deficient T cells. In
      terms of mature T cell function, a reduction in proliferation, and IL-2 and IFN
      gamma production was observed upon stimulation of P14/CNAalpha(-/-) T cells with
      the antigenic peptide. Impaired NF-AT nuclear localization was also observed.
      These results suggest that CNAalphais important for mature T cell function, but
      has a limited role in thymocyte development.

PMID- 11981810
TI  - Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting
      chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX
      CKR.
AB  - We report here the identification and characterization of murine CCX-CKR, a high
      affinity receptor for the murine beta-chemokines SLC/mCCL21, MIP-3beta/mCCL19 and
      TECK/mCCL25. Unlike most other chemokine receptors, CCX-CKR is unable to mediate
      Ca(2+) fluxes upon ligand binding when expressed in HEK293 cells. Murine CCX-CKR
      is expressed predominantly in the heart and lung, but is detectable in most
      organs using RT-PCR. Interestingly, in brain and testis, an alternative mRNA form
      of CCX-CKR exists with a unique 5' untranslated region (5'UTR) that overlaps with
      a novel acyl-CoA dehydrogenase (ACD) gene. Analysis of human CCX-CKR shows that
      the expression profiles and alternative 5'UTR are conserved. However, in man,
      there are two copies of the CCX-CKR gene, one on chromosome 3 nestled within the
      ACD homologue, and one on chromosome 6. These genes encode proteins with only one
      amino acid difference, and their expression is independently regulated. This
      study identifies murine CCX-CKR, reveals complex regulation of CCX-CKR gene
      expression in mouse and man, and is suggestive of non-leukocytic targets for MIP
      3beta/CCL19, SLC/CCL21 and TECK/CCL25.

PMID- 11981811
TI  - Th2-type granuloma development in acute murine schistosomiasis is only partly
      dependent on CD4+ T cells as the source of IL-4.
AB  - Schistosome granulomas produce IL-4, important for Th2 granuloma expression. We
      defined the origins of IL-4 within these granulomas and the role of IL-4
      producing CD4(+) T cells in Th2 granuloma development. Dispersed granuloma cells
      spontaneously produced IL-4 independently of T cells, whereas IL-5 production was
      T cell dependent. Granuloma IL-4 mRNA localized to the non-T cells and IL-5 to T
      cells. Granuloma CD4(+) T and NK cells, but not B cells produced IL-4 and IL-5 in
      vitro. B cell-/- mice generated Th2 granulomas that produced IL-4 and IL-5
      normally. Granuloma eosinophils expressed no IL-4 or IL-5 mRNA. Granulomas in WWv
      mast cell-deficient mice lacked mast cells. The dispersed granuloma cells from
      WWv mice released IL-4 only after T cell stimulation, suggesting that mast cells
      influenced the constitutive component of IL-4 production. Rag-1 animals (T/B/NK T
      cell deficient) given schistosomiasis after reconstitution with splenocytes from
      naive mice produced Th2 granulomas. Mice reconstituted to create selective CD4(+)
      T cell IL-4 knockout animals developed eosinophilic granulomas that made IL-4.
      Thus, granulomas contain several cell types that produce IL-4. Mast cells are not
      needed to form Th2 granulomas, but influence IL-4 release. Th2 granuloma
      development in schistosomiasis is only partly dependent on IL-4-producing CD4(+)
      T cells.

PMID- 11981812
TI  - Hyporesponsiveness to gammac-chain cytokines in activated lymphocytes from
      patients with systemic lupus erythematosus leads to accelerated apoptosis.
AB  - Pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) is
      unresolved. Dysregulation of programmed cell death is discussed as a pathogenetic
      factor. We have previously shown that increased in vitro apoptosis of cultured
      peripheral blood mononuclear cells (PBMC) is nonspecific for SLE. Importantly,
      however, in recent experiments with SLE PBMC from patients with infections and
      fever in vitro apoptosis was strongly accelerated. We therefore hypothesized that
      regulation of apoptosis might be disturbed in activated SLE lymphocytes. Thus, we
      generated phytohemagglutinine (PHA)/IL-2 stimulated lymphoblasts in vitro. These
      lymphoblasts readily undergo apoptosis after culture in cytokine-free medium, and
      can be rescued by addition of gammac-chain cytokines IL-2, -4, -7, or -15. In
      lymphoblasts from 60 SLE patients tested in comparison to lymphoblasts from
      normal donors cultured in parallel, we found significant hyporesponsiveness to
      gammac-chain cytokines in SLE cells. Minor differences were also seen in
      lymphoblasts from patients with other systemic autoimmunopathies (mixed
      connective tissue disease, vasculitis, n=49)and in lymphoblasts from patients
      with other autoimmune diseases (mainly rheumatoid or reactive arthritis,
      myositis, n=44). In patients with high erythrocyte sedimentation rate (> 25
      mm/h), TNF-alpha (> 6.5 pg/ml) or IL-12 (> 4.7 pg/ml) serum levels or detectable
      IFN-gamma concentrations hyporesponsiveness to gammac-chain cytokines was even
      more pronounced in SLE lymphoblasts, but not in lymphoblasts from the other
      groups. Moreover, increased apoptosis was seen in lymphoblasts from SLE patients
      with decreased complement (C)4 or elevated dsDNA antibody levels. In conclusion,
      these data suggest that in SLE patients with increased inflammatory activity
      and/or Th1 dominance signaling through gammac-chain cytokine receptors is
      deteriorated, leading to facilitated apoptosis of activated lymphocytes and
      enlarged onflow of apoptotic material.

PMID- 11981813
TI  - Modulation of chemokine receptor expression and chemotactic responsiveness during
      differentiation of human naive T cells into Th1 or Th2 cells.
AB  - Chemokines and their receptors direct movements and encounters of lymphocytes and
      professional APC into specific microenvironments of lymphoid tissues. Chemokine
      receptors such as CCR7, CXCR5 and CCR4 that are differentially expressed and
      modulated in distinct subsets of T cells contribute to establish functionally and
      spatially segregated microenvironments within secondary lymphoid tissues where T
      cell activation and differentiation occur. Here, we have explored the modulation
      of CCR7, CCR4, CCR8 and CXCR5 expression and chemotactic responsiveness to their
      ligands during commitment of human naive T cells along the Th1 or Th2
      differentiation pathway in vitro. Our results document that activation of human
      naive T cells and differentiation in Th1 or Th2 cells result in progressive down
      modulation of CCR7 expression and CCL19 responsiveness. By contrast, expression
      of CCR4 and responsiveness to CCL22 is rapidly induced at the early stages of
      both Th1/Th2 cell development. However, while CCR4 expression is further up
      regulated upon differentiation into Th2 cells, it is lost on fully differentiated
      Th1 cells. CCR8 is detected at later time points than CCR4 and exclusively on
      differentiated Th2 cells as revealed by analysis of mRNA expression and
      responsiveness to CCL1. Expression of CXCR5 is transiently induced at the early
      stages of Th cell differentiation, but with distinct kinetics in developing Th1
      and Th2 cells. Analysis of human tonsillar CD4(+) T cells reveals a consistent
      pattern of chemotactic responsiveness and chemokine receptor expression in
      distinct transitional stages of human T cell activation and differentiation in
      vivo.

PMID- 11981814
TI  - Contribution of selectin ligands to eosinophil recruitment into the skin of
      patients with atopic dermatitis.
AB  - Leukocyte extravasation is initiated by interaction with endothelial selectins
      through selectin ligands. To understand the relative roles of E- and P-selectin
      in eosinophil recruitment in inflamed skin, we examined the expression of sialyl
      Lewis x (sLex) structures and selectin ligands on eosinophils from patients with
      atopic dermatitis using whole blood flow cytometry. None of the eosinophils from
      the blood of patients expressed HECA452 (a lymphocyte receptor for skin homing)
      or CSLEX1 epitopes, and they had little avidity for soluble E-selectin. Whereas
      levels of the FH6 epitope (sialyl-dimeric Lex) varied on blood eosinophils, none
      of the infiltrative eosinophils in the skin lesions of patients expressed any
      type of sLex structures on the surface. In contrast, blood eosinophils bound to
      soluble P-selectin. The amount of P-selectin that bound to eosinophils was
      significantly greater in patients with atopic dermatitis than in healthy donors.
      PSGL-1 expression between these two groups did not differ. Furthermore,
      eosinophils expressed a large amount of alpha (1, 3) fucosyltransferase (FucT)-IV
      mRNA, but remarkably little or no FucT-VII mRNA compared with neutrophils. These
      data indicate that eosinophil interaction with endothelial P-selectin is far more
      important than interaction with E-selectin for recruitment into the inflamed skin
      of patients with atopic dermatitis. None of HECA452, 2H5, CSLEX1 or FH6 antigens
      functioned as a specific receptor to promote preferential skin infiltration via
      adhesion to endothelial E-selectin. FucT-IV in eosinophils may be more relavent
      to the generation of functional P-selectin ligand than FucT-VII.

PMID- 11981815
TI  - CD25+CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary
      hyperinflammation driven by Pneumocystis carinii in immunodeficient mice.
AB  - The CD4(+) T cell-mediated inflammatory response to Pneumocystis carinii (PC)
      critically contributes to the clinical severity of PC pneumonia. It has been
      suggested that lymphopenic conditions predispose individuals to this
      immunopathology, although the mechanisms remain poorly understood. Another set of
      evidence indicates that a subpopulation of CD4(+) T cells constitutively
      expressing the CD25 molecule prevent lymphopenia-induced autoimmunity and
      inflammatory bowel disease. We tested the ability of this CD25(+)CD4(+)
      population to regulate CD4(+) T cell-mediated inflammatory response to PC.
      Adoptive transfer of CD25(-)CD4(+) cells into PC-infected recombination
      activating gene-2-deficient mice led to lethal pneumonia within 13 days post
      transfer. PC infection appeared to trigger CD25(-)CD4(+) cells, since recipients
      with reduced PC load survived up to 5 weeks after transfer. In contrast, transfer
      of CD25(+)CD4(+) cells did not induce lethal pneumonia and prevented the
      development of the disease induced by CD25(-)CD4(+) cells. Furthermore, CD25(
      )CD4(+) cells reduced the PC load in the lung, while CD25(+)CD4(+) cells
      suppressed this immune response. Our results indicate an essential role for
      CD25(+)CD4(+) T cells in the control of PC-driven immunopathology, and suggest
      that in immunocompromised hosts PC pneumonia may result from a deficiency in
      regulatory T cells.

PMID- 11981816
TI  - IL-10 is necessary for FasL-induced protection from experimental autoimmune
      thyroiditis but not for FasL-induced immune deviation.
AB  - Ectopic expression of FasL on thyrocytes confers immune privilege status to the
      thyroid by inducing apoptosis of Fas-expressing autoimmune effector T cells and
      anti-thyroglobulin (Tg) immune deviation away from the T1 type. Fas-mediated
      apoptosis of lymphoid cells leads to rapid production of anti-inflammatory
      cytokines such as IL-10. On the other hand, cytokines play a crucial role in the
      immunoregulation and pathology of experimental autoimmune thyroiditis (EAT), and
      systemic and local administration of IL-10 has a curative effect on EAT. To test
      the effect of endogenous IL-10 production in EAT, and to find out whether IL-10
      production could be involved in FasL-induced protection, EAT was induced in IL
      10(-/-) and in IL-10(-/-)xFasL-transgenic CBA/J mice. The results demonstrated
      that wild-type and IL-10 knockout (KO) animals developed similar EAT. In
      contrast, lack of endogenous IL-10 abolished the protective effect of FasL.
      Polymorphonuclear cells were observed significantly more frequently in the
      inflammatory cell infiltrates from IL-10(-/-)xFasL animals compared to IL-10(-/-)
      animals, but they were never detected in wild-type or IL-10(+/+)/FasL-transgenic
      mice. A shift away from T1 response was observed in FasL-transgenic mice
      irrespective of their IL-10 status, demonstrating that in our model, endogenous
      IL-10 plays no part in the T1-towards-T2 anti-Tg immune balance induced by FasL.
      In summary, endogenous IL-10 is not essential in EAT, or for the immune deviation
      induced by thyroid FasL expression, whereas it is necessary for the immune
      privilege status of the thyroid conferred by FasL expression on thyrocytes.

PMID- 11981817
TI  - Alternative end joining during switch recombination in patients with ataxia
      telangiectasia.
AB  - Ataxia-Telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive
      genetic diseases with similar cellular phenotypes that are caused by mutations in
      the recently described ATM (encoding ATM) and NBS1 (encoding p95) genes,
      respectively. Both disorders are accompanied by immunodeficiency in a majority of
      patients, but the mechanism involved has as yet not been established. We
      demonstrate that in cells from A-T patients, the switch (S) recombination
      junctions are aberrant and characterized by a strong dependence on short sequence
      homologies and devoid of normally occurring mutations around the breakpoint. A
      low number of S fragments were generated in cells from NBS patients and showed
      only limited dependence on sequence identity and mutation frequencies were
      similar to those observed in normal controls. We propose that ATM and p95 are
      both involved in the final step(s) in class switch recombination with related,
      but disparate, functional roles. Thus, the general pathway involved in DNA repair
      also has a major influence on the immunoglobulin isotype switching process.

PMID- 11981818
TI  - Block of Stat-1 activation in macrophages phagocytosing bacteria causes reduced
      transcription of CIITA and consequent impaired antigen presentation.
AB  - The IFN-gamma-induced HLA class II expression in human macrophages was
      drastically reduced after phagocytosis of Escherichia coli. HLA class II down
      modulation depended on phagocytosis of bacteria and could not be reproduced by
      phagocytosis of inert particles or by treatment with lipopolysaccharide. Study of
      the kinetics and molecular analysis showed that class II molecules and
      corresponding mRNA were up-regulated at 6 h after phagocytosis of bacteria.
      Subsequently, a progressive reduction of mRNA occurred, and, at 72 h, as little
      as 25% of the class II mRNA level of IFN-gamma-treated control cells was found.
      This was due to reduced transcription of the class II transcriptional activator
      CIITA, as a consequence of reduced immediate-early inducible factor (IRF-1) and
      particularly of reduced phosphorylated Stat-1 homodimers, nuclear factors both
      necessary for optimal triggering of the CIITA promoter. Failure to sustain IFN
      gamma-induced CIITA up-modulation during phagocytosis of bacteria had functional
      implications, as human macrophages could not adequately process and present
      antigenic peptides to HLA-DR-restricted antigen-specific T cells. This is the
      first evidence that phagocytosis of bacteria can down-modulate HLA class II
      expression in normal human macrophages by acting at the level of expression of
      CIITA.

PMID- 11981819
TI  - The CD14+CD16+ monocytes in erysipelas are expanded and show reduced cytokine
      production.
AB  - In human peripheral blood the classical CD14(++)DR(+) monocytes and the pro
      inflammatory CD14(+)CD16(+)DR(++) monocytes can be distinguished. In erysipelas
      we found strongly increased numbers of CD14(+)CD16(+) monocytes on the day of
      diagnosis (day 1) in 11 patients with an average of 150.5+/-76.0 cells/microl,
      while 1 patient had low levels (35 cells/microl, control donors 48.8+/-19.8
      cells/microl). The classical monocytes were only moderately elevated in the
      erysipelas patients (factor 1.7 as compared to controls). Patients exhibited
      increased body temperature, erythrocyte sedimentation rate and increased serum
      levels for C-reactive protein (CRP), IL-6 and macrophage-colony-stimulating
      factor. Among these, body temperature and CRP showed a significant correlation to
      the numbers of CD14(+)CD16(+) monocytes. In 4 of 4 patients with high levels of
      CD14(+)CD16(+) monocytes, these levels returned to that seen in controls by day 5
      of antibiotic therapy. Determination of intracellular TNF was performed by three
      color immunofluorescence and flow cytometry after ex vivo stimulation with
      lipoteichoic acid, a typical constituent of streptococci. Here, patient
      CD14(+)DR(++) pro-inflammatory monocytes showed a twofold lower level of
      intracellular TNF. By contrast, expression of TNF was unaltered in the classical
      CD14(++) monocytes. These data show that in erysipelas the pro-inflammatory
      CD14(+)CD16(+)DR(++) monocytes are substantially expanded and selectively
      tolerant to stimulation by streptococcal products.

PMID- 11981820
TI  - Distinctive signaling pathways through CD82 and beta1 integrins in human T cells.
AB  - CD82, a member of tetraspan family (tetraspanin), is a multifunctional molecule
      that is involved in cell activation, costimulation, and cell spreading of T
      cells. Here we show that immobilized anti-CD82 monoclonal antibody (mAb) as well
      as anti-alpha4beta1 integrin mAb induced tyrosine phosphorylation of pp105/Crk
      associated substrate lymphocyte type (Cas-L) in human peripheral T cells and H9
      cells. Furthermore, one of anti-CD82 mAb (8E4), which induces homotypic
      aggregation of T cells and H9 cells but has no costimulatory activity, partially
      inhibited very late antigen (VLA)-4 integrin ligand-mediated costimulation of T
      cells, whereas it failed to inhibit VLA-5 integrin ligand-mediated costimulation.
      To further elucidate the relationship between CD82- and VLA-4-mediated signaling
      pathways we defined the IL-2 production by the costimulation of Jurkat T cells
      with marginal amount of Cas-L, and subsequently found that mAb against CD82 had
      strong costimulatory activity to CD3/TCR, whereas mAb against beta1 failed to do
      so in those cells. We have further demonstrated that this discrepancy between
      beta1 integrin- and CD82-mediated costimulation partly lies in differential
      activation of NF-AT, AP-1, and NF-kappaB in Jurkat T cells. In this study,
      although some functional overlap exists, we provide evidence for distinctive
      signaling of CD82- and beta1 integrin-mediated costimulation at the
      transcriptional level of IL-2 gene.

PMID- 11981821
TI  - Cross-sensitization to haptens: formation of common haptenic metabolites, T cell
      recognition of cryptic peptides, and true T cell cross-reactivity.
AB  - To analyze T cell cross-reactivity to para-compounds, we established CD4(+) T
      cell hybridomas from mice immunized with adducts of self-globin and one of three
      different para-compounds: p-aminophenol, p-phenylenediamine, or Bandrowski's
      base. Some of the hybridomas obtained reacted not only to the immunizing antigen,
      but also to metabolically related para-compounds, bound to the same protein, thus
      suggesting formation of common metabolites. Other hybridomas cross-reacted to
      globin adducts of metabolically unrelated para-compounds, which denotes them as
      truly cross-reactive cells whose TCR failed to distinguish among the different
      haptens. One of these hybridomas also reacted against a non-haptenated, cryptic
      peptide of hemoglobin but not to the full-length native protein. As this
      hybridoma reacted even more strongly to the respective peptide after it was
      haptenated, recognition of the native, cryptic peptide was apparently due to true
      cross-reactivity. To conclude, true T cell cross-reactivity to haptens does
      occur, as well as the formation of a common reactive metabolite, and T cell
      recognition of cryptic self-peptides may underlie cross-sensitization to
      chemicals.

PMID- 11981822
TI  - Structure, diversity and expression of the TCRdelta chains in the Mexican
      axolotl.
AB  - Mammals and birds have two major populations of T cells, based on the molecular
      composition and biological properties of their antigen receptors (TCR). alpha
      beta T cells recognize antigenic peptides linked to major histocompatibility
      complex (MHC) molecules, and gamma delta T cells recognize native peptide or non
      peptide antigens independently of MHC. Very little is known about gamma delta T
      cells in ectothermic vertebrates. We have cloned and characterized the TCRdelta
      chains of an urodele amphibian, the Mexican axolotl (Ambystoma mexicanum). The
      Cdelta domain is structurally similar to its mammalian homologues and the
      transmembrane domain is very well conserved. Four of the six Valpha regions that
      can associate with Calpha (Valpha2, Valpha3, Valpha5 and Valpha6) can also
      associate with Cdelta, but no specific Vdelta regions were found. This suggests
      that the axolotl TRD locus is nested within the TRA locus, as in mammals, and
      that this organization has been present in all tetrapod vertebrates and in the
      common ancestor of Lissamphibians and mammals, for over 400 million years. Two
      Jdelta regions were identified, but no Ddelta segments were clearly recognized at
      the Vdelta-Jdelta junctions. This results in shorter and less variable CDR3 loops
      than in other vertebrates and the size range of the Vdelta-Jdelta junctions is
      similar to that of mammalian immunoglobulin light chains. Equivalent quantities
      of TRD mRNA were found in the lymphoid organs, and in the skin and the intestines
      of normal and thymectomized axolotls. The analysis of several Valpha/delta6
      Cdelta and Vbeta7-Cbeta junctions showed that both the TCRdelta and the TCRbeta
      chains were limited in diversity in thymectomized axolotls.

PMID- 11981823
TI  - The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in
      promoting C3 fragment deposition and membrane attack complex formation on normal
      peripheral human B cells.
AB  - Normal human B lymphocytes are known to activate the alternative pathway (AP) of
      complement, leading to C3-fragment deposition and membrane attack complex (MAC)
      formation. The process is mediated via complement receptor type 2 (CR2, CD21),
      with complement receptor type 1 (CR1, CD35) playing a subsidiary role. In this
      study, we examine the relative contributions of CR1 and CR2 to the deposition of
      C3 fragments and MAC on B lymphocytes under circumstances where all complement
      pathways are operational. C3-fragment deposition and MAC formation were assessed
      on human peripheral B lymphocytes in the presence of 30% autologous serum.
      Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted
      in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC
      formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1
      binding-site resulted in significant reduction of both C3-fragment deposition
      (22.0+/-14.5%) and MAC formation (47.4+/-13.8%). Both the lack of CR2 influence
      on MAC formation and the promotion of C3-fragment deposition by CR1 are in
      striking contrast to the situation where only the AP is operational. The presence
      of erythrocytes (E) bearing CR1, however, markedly reduced both C3-fragment
      deposition and MAC formation. Our data suggest that C3-fragment deposition and
      MAC formation on B lymphocytes in vivo may involve both AP and classical pathway
      activation, with CR1 contributing significantly to the latter. On the other hand,
      the presence of extrinsic CR1, on E, may serve to limit spontaneous MAC formation
      and thereby ensure cell survival in the circulation.

PMID- 11981824
TI  - The effect of the interferon-gamma-inducible processing machinery on the
      generation of a naturally tumor-associated human cytotoxic T lymphocyte epitope
      within a wild-type and mutant p53 sequence context.
AB  - The human wild-type (wt) p53.264-272 peptide is a universal tumor antigen and
      recognized by HLA-A*0201 (A2.1)-restricted CTL. Generation of this epitope by
      constitutive 20S proteasomes is prevented by a p53 R to H hotspot mutation at the
      C-terminal flanking residue 273. We report on the impact of the interferon-gamma
      (IFN-gamma)-inducible proteasomal activator PA28 (11S regulator) and the
      immunoproteasome on the in vitro and cellular processing of wt and mutant (mut)
      p53 substrates. We found that production of the antigenic 264-272 peptide from wt
      p53 by constitutive as well as immunoproteasomes is accelerated and amplified by
      the PA28 activator. PA28 and (immuno)proteasomes were not capable to reconvert
      the resistance of epitope release from mut p53. Maximum and accelerated antigen
      production in vitro and on the cellular level required the IFN-gamma-inducible
      interaction of immunoproteasomes and PA28. We conclude that efficient processing
      of p53.264272 from wt p53 is governed by the proteasome/PA28 complex. These
      studies have important implications for p53-specific cancer immunotherapy and
      demonstrate that the effects of the immunoproteasome and PA28 are influenced by
      the individual epitope and its flanking sequence context.

PMID- 11981825
TI  - Innate and cognate mechanisms of pulmonary eosinophilia in helminth infection.
AB  - Passage of helminth larvae through the lungs can cause pulmonary eosinophilia
      that may have evolved as a means of parasite attrition. If allergic responses
      represent a misdirected activation of this arm of the immune system, then
      mechanisms governing eosinophil recruitment during infection would be expected to
      be closely related to those seen in allergy. We studied primary Necator
      americanus infection and compared this to multiply-infected or vaccinated mice.
      The arrival of larvae in the lungs triggered rapid eosinophil recruitment, which
      was greatly enhanced in previously sensitized mice. Interestingly, the presence
      of larvae in the lung was sufficient to trigger eosinophil chemoattractant
      production, including the chemokines eotaxin and MIP-1alpha, and was not enhanced
      by prior exposure to the parasites. Infection stimulated IL-5 production in all
      groups; however, this and IgE production were greatly enhanced in sensitized
      animals. Elevated IL-5 increased bone marrow production of eosinophils, and
      eosinophilia was abrogated by treatment with anti-IL-5 antibody. Therefore,
      trapping of larvae in the pulmonary vasculature is sufficient to trigger
      eosinophil recruitment, by induction of chemokines and IL-5. Primed cognate Th2
      immunity does not increase local chemokine production, but does increase IL-5
      production, which greatly enhances the availability of eosinophils for
      recruitment to the lung.

PMID- 11981826
TI  - Nonspecific esterase released from thymic macrophages accumulates in the
      apoptotic thymocytes: an indication for this enzyme participating in the
      clearance of apoptotic thymocytes.
AB  - In the mouse thymus, a large number of developing thymocytes die through
      apoptosis each day. It has been proposed that thymic macrophages are responsible
      for clearance of the massive number of thymocytes that die through apoptosis. The
      detailed clearance mechanism by which macrophages remove the apoptotic cells is
      not clear. Our in vitro studies in this report show that nonspecific esterase
      (NSE), a cytochemical marker enzyme of macrophages, was secreted from thymic
      macrophages as a consequence of stimulation by interaction with thymocytes, and
      the esterase accumulated in these macrophage-binding thymocytes (MBT). TUNEL
      staining demonstrated that these MBT were undergoing apoptosis. The inability to
      exclude eosin Y and the presence of pores on the plasma membrane were further
      evidence for the disintegration of these MBT. In vivo, the release of NSE was
      evident by the presence of NSE activity in the extracellular space between the
      macrophages and apoptotic thymocytes under the transmission electron microscope
      after dexamethasone injection, which causes massive apoptosis of thymocytes.
      Inhibition study showed that the inhibition of NSE delayed the MBT progressing to
      the late apoptotic phase. These results suggest that the NSE released from
      macrophages is involved in the clearance of apoptotic thymocytes.

PMID- 11981827
TI  - Resistance to TGF-beta1-mediated growth inhibition correlates with sustained
      Smad2 phosphorylation in primary murine splenocytes.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that
      regulates cell growth and differentiation in many types of cells. TGF-beta1 is
      especially known to exert a variety of regulatory functions in the immune system,
      such as T cell differentiation and T cell function. Signal transduction of TGF
      beta1 is mediated by phosphorylation of R-Smads upon receptor activation. Hetero
      oligomers of R- and Co-Smads translocate into the nucleus and regulate
      transcription of specific target genes. Here we describe the effect of long-term
      exposure to TGF-beta1 on the effector function of differentially stimulated
      primary murine splenocytes and purified primary murine CD8(+) cytotoxic T cells.
      Long-term exposure to TGF-beta1 results in non-responsiveness to TGF-beta1
      induced Smad2 phosphorylation. This is seen either by no phosphorylation or
      sustained phosphorylation of Smad2. Furthermore, we observed a strong correlation
      between sustained Smad2 phosphorylation and resistance to TGF-beta1-mediated
      growth inhibition. In contrast, splenocyte cultures strongly growth inhibited by
      TGF-beta1 showed no Smad2 phosphorylation. Lytic activity of these cultures,
      however, was found to be suppressed regardless of proliferation properties and
      Smad2 phosphorylation pattern. These findings may contribute to understanding the
      mechanisms of how TGF-beta1 suppresses immune responses and promotes tumor
      progression.

PMID- 11981828
TI  - Chronic lymphocytic leukemia B cells are endowed with the capacity to attract
      CD4+, CD40L+ T cells by producing CCL22.
AB  - The natural history of B-chronic lymphocytic leukemia (CLL) is not entirely
      explained by intrinsic defects of the neoplastic cell, but is also favored by
      microenvironmental signals. As CLL cells retain the capacity to respond to CD40
      ligand (CD40L) and as CD4(+) T cells are always present in involved tissues, we
      asked whether malignant CLL cells might produce T cell-attracting chemokines. We
      studied the chemokine expression of CD19(+)/CD5(+) malignant B cells from
      peripheral blood (PB), lymph nodes (LN) or bone marrow (BM) of 32 patients and
      found a major difference. LN- and BM-, but not PB-derived cells, expressed a
      readily detectable reverse transcription-PCR band for CCL22 and one for CCL17 of
      variable intensity. CD40 ligation of PB cells induced the mRNA expression of both
      CCL22 and CCL17. CCL22 was also released in the culture supernatants. These
      supernatants induced the migration of activated CD4(+), CD40L(+) T cells
      expressing the CCL22 receptor, CCR4. T cell migration was abrogated by anti-CCL22
      antibodies. Immunohistochemistry and cytofluorography studies revealed that a
      proportion of CD4(+) T cells in CLL LN and BM expressed CD40L. Our data
      demonstrate that malignant CLL cells chemo-attract CD4(+) T cells that in turn
      induce a strong chemokine production by the leukemic clone, suggesting a vicious
      circle, leading to the progressive accumulation of the neoplastic cells.

PMID- 11981829
TI  - T cell-dependent and -independent pathways to tissue destruction following herpes
      simplex virus-1 infection.
AB  - Viral infections can trigger tissue destruction through innate and/or adaptive
      immune mechanisms. Here we show that these pathways can be differentially
      activated after infection by different strains of the herpes simplex virus-1 (HSV
      1) virus. Infection of murine corneal tissue by HSV-1 (KOS) triggers an
      autoreactive clone of CD4 cells that is cross-reactive with an HSV-1 epitope to
      initiate corneal destruction. In contrast, ocular infection by the HSV-1 (RE)
      strain induces murine corneal destruction through direct, T cell-independent,
      activation of the innate immune system. Although the relative role of these two
      pathways to blindness following clinical HSV-1 ocular infection is unknown, this
      analysis suggests a general experimental approach to evaluate the relative
      contribution of adaptive and innate immune mechanisms to virally induced host
      tissue destruction.

PMID- 11981830
TI  - Application of phage display peptide library to autoimmune diabetes:
      identification of IA-2/ICA512bdc dominant autoantigenic epitopes.
AB  - Autoantigenic epitope mapping represents a critical issue in autoimmune diseases.
      The islet tyrosine phosphatase-like protein IA-2/ICA512bdc is a major autoantigen
      in type 1 diabetes (IDDM), but the epitopes responsible for autoantibody binding
      have been only partially defined. The aim of our study was to identify ICA512bdc
      epitopes, and in particular mini-epitopes, utilizing a novel strategy for
      autoimmune diseases. The study was performed in three sequential steps: (1)
      construction of a lambda-phage surface-displayed ICA512bdc cDNA library with the
      methodology of tagged random priming with peptides displayed as a fusion to the C
      terminus of the capsid protein D; (2) affinity selection of the resulting
      library, followed by immunoscreening, enzyme-linked immunosorbent assay and
      sequence analysis of positive clones, and (3) radioimmunoprecipitation to detect
      autoantibodies to the selected clones. This strategy resulted in the
      identification of two epitopes (IA-2 residues 761 - 964 and 929 - 979), which
      were recognized by 100 % and 62.9 % ICA512bdc-positive IDDM patients,
      respectively. Interestingly, the larger clone was detected also by a proportion
      (16.7 %) of new onset ICA512bdc-negative patients, thus suggesting that this
      region contains not only the main autoantigenic repertoire of ICA512bdc molecule,
      but is able to detect IA-2 autoantibodies in even higher percentages of patients.
      In addition, this study showed the existence of multiple epitopes located in the
      C-terminal domain of the IA-2 protein, one of which is formed by the 50 C
      terminal amino acids, and provided evidence that the strategy used represents a
      valid tool for identification of epitopes within autoantigenic molecules.

PMID- 11981831
TI  - IL-4 secreted from individual naive CD4+ T cells acts in an autocrine manner to
      induce Th2 differentiation.
AB  - Naive CD4(+) T cell populations rapidly produce small amounts of IL-4 in response
      to T cell receptor-mediated stimulation and may undergo Th2 differentiation
      without exogenous IL-4. Whether this is due to autocrine IL-4-stimulation or the
      production of IL-4 by an infrequent naive cell has not been determined. Here we
      show that single CD4(+) T cells from RAG2-/- T cells receptor transgenic mice
      primed with their cognate antigen give rise to IL-4-producing cells at a similar
      frequency whether primed with or without added IL-4, but not if anti-IL-4 is
      added to the culture. Thus, each founder cell or one or more of its early
      daughters can produce sufficient IL-4 to drive Th2 differentiation. This
      indicates that autocrine IL-4 production by naive CD4 T cells can drive the
      appearance of Th2 cells.

PMID- 11981832
TI  - Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the
      thymic microenvironment.
AB  - The process of thymocyte differentiation occurs within the context of the thymic
      microenvironment, in which T cell precursors interact with thymic
      microenvironmental cells and extracellular matrix. Here we studied the expression
      of galectin-3, a beta-galactoside binding lectin, in the thymus of young adult
      mice. Galectin-3 was found mainly in the medulla and to a lesser extent in the
      cortex. We further showed that distinct microenvironmental elements, such as
      thymic epithelial cells, the epithelial component of thymic nurse complexes and
      phagocytic cells of the thymic reticulum produce, secrete and accumulate galectin
      3 on the cell surface. Functionally, galectin-3-enriched medium inhibited in
      vitro thymocyte interactions with thymic microenvironmental cells, accelerated
      the release of thymocytes from thymic nurse cells and inhibited the
      reconstitution of these lymphoepithelial complexes. These effects were blocked by
      exogenous lactose (Galbeta1-4Glc), but not melibiose (Galalpha1-6Glc), and by a
      monospecific anti-galectin-3 antibody. Recombinant galectin-3 also inhibited
      thymocyte/thymic epithelial cell interactions. Our data indicate that
      intrathymically produced galectin-3 disrupts thymocyte/microenvironmental cell
      interactions, thus acting as a de-adhesion molecule.

PMID- 11981833
TI  - Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin.
AB  - The integrin alpha4beta7 binds to MAdCAM-1 and contributes to homing of
      lymphocytes to gut and other mucosal tissues. In humans, the alpha4beta7(hi)
      subset of circulating memory cells appears to have been primed in mucosal
      tissues. The factors that determine whether alpha4beta7(lo) naive cells become
      alpha4beta(hi) or alpha4beta7(-) cells upon differentiation are poorly understood
      but could include an influence of the activating antigen-presenting cell. To
      address this point, the induction of alpha4beta7 following activation of mouse
      cells with the APC-dependent stimulus soluble anti-CD3 has been examined. Almost
      all mouse T cells freshly isolated from mesenteric lymph nodes (MLN) and
      peripheral (PLN; axillary, brachial and inguinal) lymph nodes stained only weakly
      for alpha4beta7 but a subpopulation became alpha4beta7(hi) upon activation with
      anti-CD3 in a cell cycle- and accessory cell-dependent manner. A small proportion
      (approximately 1.5 %) of the starting cells gave rise to alpha4beta7(hi) cells
      after culture. A higher proportion of alpha4beta7(hi) cells were generated in MLN
      than PLN cultures. Peyer's patch cultures gave intermediate values. In crossover
      experiments, MLN dendritic cells (DC) induced higher proportions and numbers of
      alpha4beta7(hi) cells than PLN DC irrespective of the source of T cells.
      Therefore, in addition to their other immunoregulatory roles, DC have the
      potential to shape immune responses by influencing the homing of the lymphocytes
      they activate.

PMID- 11981834
TI  - CD40/CD40 ligand interactions in the host defense against disseminated Candida
      albicans infection: the role of macrophage-derived nitric oxide.
AB  - CD40L interaction with CD40 is required for normal cellular immune responses such
      as T cell-mediated activation of monocytes/macrophages, proinflammatory cytokine
      production, and leukocyte extravasation. We investigated the role of CD40/CD40
      ligand (L) interactions during disseminated candidiasis in CD40L knockout (CD40L
      /-) mice. While early during infection there were no differences in the Candida
      albicans outgrowth in the organs of wild-type and knockout mice, the CD40L-/-
      mice had a significantly increased yeast load in the kidneys compared to CD40L+/+
      mice late during infection. Similar effects were observed in CD40L+/+ mice in
      which CD40 ligation was blocked by a neutralizing anti-CD40 antibody. The peak
      TNF-alpha plasma concentrations were significantly lower in the CD40L-/- mice
      than in CD40L+/+ mice. C. albicans-stimulated production of nitric oxide (NO) by
      peritoneal macrophages from CD40L-/- in vitro was significantly lower than that
      of control mice, and this was responsible for a reduced candidacidal activity of
      CD40L-/- macrophages. The role of endogenous NO synthesis induced by CD40
      ligation for the defense against disseminated candidiasis was further
      demonstrated by the absence of these effects in knockout mice deficient in
      inducible NO-synthase. In conclusion, absence of CD40/CD40L interactions results
      in increased susceptibility to disseminated infection with C. albicans through
      decreased NO-dependent killing of Candida by macrophages.

PMID- 11981835
TI  - Cytotoxicity and interleukin-1beta processing following Shigella flexneri
      infection of human monocyte-derived dendritic cells.
AB  - Shigella flexneri infection of macrophages (MPhi) leads to activation of caspase
      1 by the IpaB virulence factor, which induces rapid cell death and release of
      mature IL-1beta. Here we show that S. flexneri infection of human monocyte
      derived dendritic cells (DC) also results in rapid IpaB-dependent death.
      Cytotoxicity is only partially blocked by the caspase-1 inhibitor YVAD, but
      completely blocked by the pan-caspase inhibitor z-VAD. Cytotoxicity is also
      partially blocked by glycine without affecting caspase-1-dependent IL-1beta
      processing, and treatment with glycine and YVAD completely blocks cytotoxicity,
      implying that glycine inhibits a caspase-1-independent cytotoxic mechanism. S.
      flexneri infection of LPS-pre-treated DC and Mphi results in comparable release
      of mature IL-1beta, although DC release significantly less IL-18 than MPhi. IL
      1beta release from infected DC occurs within 3 h of the initial LPS pre
      stimulation signal, implying that infection of DC will contribute towards
      induction of the early inflammatory response. The rapid death of DC during the
      early stages of shigellosis is likely to have adverse consequences for generation
      of adaptive immunity.

PMID- 11981836
TI  - CD26 is expressed on a restricted subpopulation of dendritic cells in vivo.
AB  - Two major sub-populations of dendritic cells (DC) are present in afferent lymph
      draining the skin of cattle distinguished by expression of signal regulator
      protein alpha (SIRPalpha). The SIRPalpha(-) population expresses the
      uncharacterized bovine WC10 antigen (Ag). Initial N-terminal sequencing of the
      WC10 protein purified by affinity chromatography showed significant homology with
      human CD26. A cDNA encoding bovine CD26 was cloned and the recombinant molecule
      expressed in COS-7 cells. Transfectants abrogated the ability of macrophage
      derived chemokine (MDC) to cause a calcium flux in bovine PBMC indicating
      enzymatic activity characteristic of CD26. They also stained with WC10 monoclonal
      antibody confirming that the Ag is CD26. This is the first description of CD26
      expression by DC in vivo or in vitro. It is expressed on a sub-population of ex
      vivo DC in afferent lymph draining the skin and on sub-populations of DC isolated
      from prescapular and mesenteric lymph nodes draining the skin or intestine,
      respectively. CD26 is an exopeptidase with specificity for motifs within the
      receptor-binding domain of several chemokines including MDC. CD26 mediated
      truncation of MDC affects the Th cell response effected by the chemokine and may
      produce a Th1 bias. Transcripts for MDC were present in both CD26(+) and CD26(-)
      DC, thus CD26 mediated modification of MDC may bias the immune response induced
      in naive T cells by DC.

PMID- 11981837
TI  - Distinct expression of cyclooxygenase-1 and -2 in the human thymus.
AB  - Cyclooxygenase (COX)-1 and -2 catalyze the formation of prostaglandins (PG).
      Given the role of COX and PG during intrathymic T cell development in the mouse,
      we investigated the expression and localization of these isozymes in the human
      thymus. mRNA and proteins correspondent to COX-1 and -2 were observed from whole
      thymus extracts. By immunohistochemistry, COX-2 was selectively localized in the
      medulla and it was predominant in a subset of stromal cells. By contrast, COX-1
      was diffusely and exclusively present in the cortex, both in thymocytes at early
      stages of differentiation and in cytokeratin-positive epithelial cells, as
      demonstrated by double immunostaining and flow cytometry analysis. COX-2-positive
      cells in the medulla expressed cytokeratin and HLA-DR molecules, but they were
      negative for dendritic or macrophagic antigens. In addition, COX-2-positive cells
      expressed both the epidermal growth factor receptor and its ligand, the
      transforming growth factor-alpha. The inducible isoform of the PGE(2) synthase
      was also present in the same cells, while was absent from COX-1-expressing cells
      of the cortex. Finally, electron microscopy confirmed that COX-2 was mainly
      localized in the cytoplasm of cytokeratin-positive cells, along the rough
      endoplasmic reticulum. In conclusion, COX-2 and the inducible isoform of PGE(2)
      synthase appear to be constitutively and selectively present in medullary
      epithelial cells of the human thymus, whereas COX-1 is predominantly present in
      the thymic cortex, both in the stroma and in developing thymocytes.

PMID- 11981838
TI  - Stable lymphocyte contact induces remodeling of endothelial cell matrix receptor
      complexes.
AB  - Endothelial cells (EC) actively participate in lymphocyte transendothelial
      migration by remodeling their actin cytoskeleton. We studied the endothelial cell
      abluminal matrix receptor (focal adhesion, FA) complexes to determine if these
      structures were remodeled following lymphocyte adhesion. Lymphocytes (PBL) were
      isolated from whole blood and added to cultured EC. Lectin-stimulated PBL adhered
      to EC spontaneously, whereas adhesion of freshly isolated lymphocytes to EC was
      induced by pre-treatment with MCP-1 or activating anti-CD11a mAb. Sustained
      adhesion between lymphocytes and EC resulted in a significant, contact-dependent
      decrease in paxillin incorporation into the FA following 15, but not 5, min of
      contact. EC FA remodeling was associated with increased phosphorylation of pp125
      FA kinase. Pretreatment of the EC with an activating beta1 integrin monoclonal
      antibody, TS2/16, prevented lymphocyte-stimulated FA remodeling. Further, TS2/16
      pretreatment inhibited transendothelial migration of lymphocytes and beta1
      integrin-deficient JY lymphoblasts. These data demonstrate that sustained
      lymphocyte adhesion induces remodeling of EC FA structures and that this
      remodeling event is required for efficient lymphocyte transendothelial migration
      in vitro.

PMID- 11981839
TI  - Active trans-synaptic capture of membrane fragments by natural killer cells.
AB  - Prior to delivery of a lethal hit, NK cells form an immunological synapse to scan
      the target cells and engage their activatory and inhibitory receptors. Using
      freshly isolated NK cells, IL-2-activated polyclonal NK bulk or the NKL cell
      line, we report here that early during this recognition process, human NK cells
      actively capture target cell membrane fragments. This novel NK cell function
      occurs via the immunological synapse, is controlled by Src kinase, ATP, Ca(2+)
      and PKC and involves rearrangements of the actin cytoskeleton. Furthermore, this
      process is down-regulated by signals emanating from inhibitory NK receptors
      recognizing protective MHC class I alleles.

PMID- 11981840
TI  - CD2 physically associates with CD5 in rat T lymphocytes with the involvement of
      both extracellular and intracellular domains.
AB  - T lymphocytes can be activated and induced to proliferate through stimulation of
      the CD2 glycoprotein with functional combinations of CD2 antibodies. However,
      this mechanism of signal transduction via CD2 is still not fully understood. We
      have investigated which molecules on the T cell surface preferentially associate
      in Cis with CD2 and may regulate its signaling properties. Though a
      quantification method we found that CD5 represents the antigen capable of co
      precipitating a larger proportion of CD2. Using co-capping assays and
      immunoprecipitations from cell lysates, we show that an association between CD2
      and CD5 can be found in rat thymocytes, T lymphocytes and in a thymoma cell line.
      Possibly, this interaction is a direct one, since CD2 and CD5 transiently
      expressed in Cos7 cells co-precipitate each other. Furthermore, using CD2
      chimeric proteins containing different domains of CD2, expressed in Cos7 cells as
      well as in stably transfected Jurkat cells, we show that the interaction between
      CD2 and CD5 is held at both the intra- and extracellular levels, but does not
      involve the transmembrane domain. The fact that both the extracellular and the
      cytoplasmic domains of CD2 interact with CD5 suggests a specific and tight
      association between the two molecules, possibly relevant for the fine-tuning of
      signal transduction in T lymphocytes.

PMID- 11981842
TI  - Direct chemiluminescent immunodetection of proteins in agarose gels.
AB  - Chemiluminescent immunodetection of proteins separated by polyacrylamide gel
      electrophoresis is generally performed only after Western blotting. Agarose gels
      are adequately permeable to allow immunoprobing directly in the gel.
      Chemiluminescent substrates had not been applied for direct immunoprobing of
      agarose gels. In a comparison with direct immunostaining of fibrinogen
      derivatives with horse radish peroxidase (HRP)-conjugated primary antibody using
      3,3'-diaminobenzidene (DAB) yielding a sensitivity in the low nanogram range, a
      luminol-based chemiluminescent detection extended sensitivity to the mid-picogram
      range with seemingly no interference from either regular or glyoxyl agarose gels.
      The high sensitivity of chemiluminescence extends utility of direct immunoprobing
      of either agarose or glyoxyl agarose composite gels for detection and measurement
      of both high and low molecular weight proteins/peptides which are not easily
      detected/measured by Western blotting. However, due to the thickness of the gels,
      direct immunoprobing can be quite laborious. To eliminate that drawback, we
      describe a simplified approach, converting the thick gels to thin ones prior to
      probing, that makes direct immunoprobing as easy as Western blotting.

PMID- 11981843
TI  - Electroelution without gel sectioning of proteins from sodium dodecyl sulfate
      polyacrylamide gel electrophoresis: fluorescent detection, recovery, isoelectric
      focusing and matrix assisted laser desorption/ionization-time of flight of the
      electroeluate.
AB  - A method of direct electroelution of intact proteins, without gel sectioning and
      orthogonal to the orientation of electrophoretic migration, was developed in
      application to Novex gels, using a simple home-made experimental setup. Six model
      proteins covering the molecular mass range of 14-120 kDa were subjected to sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), stained with an
      aqueous solution of the fluorescent dye, SYPRO-red, and electroeluted from the
      intact gel. The sensitivity of visual detection was 0.1-0.2 microg upon
      illumination by a green laser and 0.5-1 microg of protein on side-ways UV
      illumination. Duration (for each protein) and field strength were optimized to
      render protein electroelution from the gel near-quantitative (above 80%) and
      relatively fast (1-12 min at 1 kV). At a given field strength, the optimal
      duration was found to be inversely proportional to the mobility of proteins in
      SDS-PAGE. Sequential ultrafiltration was evaluated as a simple approach to
      concentrate electroeluted proteins and deplete SDS to a level compatible with
      mass spectrometry of proteins: protein yields in the electroeluate were 25-33%
      (depending on the protein used) after three steps of ultrafiltration with water.
      The analysis of the electroeluate by isoelectric focusing in an immobilized pH
      gradient, to reveal protein heterogeneity under a single SDS-PAGE band (prior,
      e.g., to mass spectrometric analysis), was demonstrated.

PMID- 11981844
TI  - Combination of zymography and immunodetection to analyze proteins in complex
      culture supernatants.
AB  - The physiological function of an allergen might be an important factor for the
      allergenicity. The major grass pollen allergen Phl p 1 shows sequence
      similarities to the consensus sequences of cysteine proteases. However, up to
      now, the proteolytic activity of Phl p 1 is controversial. The culture
      supernatant of Phl p 1-transfected clones from Pichia pastoris showed a
      proteolytic activity but this might be due to Phl p 1 or irrelevant yeast
      contaminants. To solve this question, we made use of the zymogram technique and
      improved it. Substrate as well as substrate concentration was changed from 1%
      casein to 0.25% skimmed milk powder. For staining, we used a colloidal Coomassie
      stain (RotiBlue) with a higher sensitivity and better practicability than the
      conventional Coomassie staining. The proteins in the zymogels and in the SDS-PAGE
      gels showed similar electrophoretic mobility. Furthermore, the zymogels could be
      blotted and immunostained. Thus, the molecular mass of the proteolytic bands
      could be determined and directly compared with immunoblotting results. To clearly
      assign the protease, we separated the culture supernatant of the Phl p 1
      transfected P. pastoris clone by affinity chromatography with monoclonal
      antibody. Our studies demonstrate that the proteolytic activity did not belong to
      the recombinant allergen but to the yeast proteins. The enzyme was classified by
      zymogram inhibition tests as a strong serine protease.

PMID- 11981845
TI  - Electrophoretic studies on the phosphorylation of stathmin and mitogen-activated
      protein kinases in neuronal cell death induced by oxidized very-low-density
      lipoprotein with apolipoprotein E.
AB  - In the central nervous system, stressful conditions can easily cause the
      oxidation of lipoprotein particles, followed by the oxidative modification of
      apolipoproteins such as apolipoprotein E (apoE) and the production of free
      radicals and aldehydes. We have confirmed that oxidized very-low-density
      lipoprotein (VLDL) inhibits the proliferation, viability and differentiation of
      neuronal PC12 cells leading to cell death. The cells internalized intact apoE,
      but did not internalize oxidized apoE. The phosphorylation of stathmin and
      various mitogen-activated protein (MAP) kinases including extracellular signal
      regulated protein kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) was
      examined in PC12 cells exposed to native and oxidized VLDL, H(2)O(2) (which
      generates free radicals), and 4-hydroxy-2-nonenal (HNE) (an aldehyde). Oxidized
      VLDL and H(2)O(2) reduced stathmin phosphorylation while HNE increased it,
      suggesting that oxidized VLDL and H(2)O(2) stimulated similar signal transduction
      pathways. Based on the results, free radicals, but not aldehydes may play a major
      role in the neuronal cell death induced by lipoprotein oxidation. Furthermore,
      the phosphorylation status of MAP kinases indicated that the activation of the
      JNK cascade might be required for neuronal cell death.

PMID- 11981846
TI  - Comparison of extraction methods for the recovery, amplification and species
      specific analysis of DNA from bone and bone meals.
AB  - We report the effect of several parameters on the efficiency of recovery of DNA
      from animal bones. The effects of preheating the samples (at either 60 degrees C
      or 100 degrees C) at different intervals (from 1 h to overnight) in different
      media (water, 0.5 M ethylenediaminetetraacetic acid (EDTA), or 0.5 M EDTA + 0.05%
      sodium dodecyl sulfate (SDS) were investigated. The effect of slight (5 min) or
      intense (30 min) pretreatments with ultrasound was also evaluated. Several
      different treatments with proteinase K (ranging from 200 to 800 microg, and
      lasting from 1 to 3 h) at 65 degrees C were also considered. Additionally, two
      different DNA extraction methods (based on silica resins and purification
      columns, respectively) were evaluated. The recovery of DNA from the samples was
      40% higher when the bones were preheated in 0.5 M EDTA at 60 degrees C for 1 h,
      this being followed by treatment with 800 microg of proteinase K for 3 h. The DNA
      thus obtained was successfully amplified by polymerase chain reaction (PCR) using
      a set of primers specific to a 359 bp region of the mitochondrial cytochrome b
      gene, and the species of origin were identified by visualizing the restriction
      fragment length polymorphism (RFLP) with the endonucleases PalI and MboI.

PMID- 11981847
TI  - Circular dichroism signatures of features simultaneously present in structured
      guanine-rich oligonucleotides: a combined spectroscopic and electrophoretic
      approach.
AB  - In order to identify possible signatures of the most typical structures adopted
      by guanine-rich oligonucleotides, we submitted them to the crossed fire of
      circular dichroism (CD) and electrophoresis. These signatures show up in the
      circular dichroism spectra even when simultaneously present within the same
      molecule. Guanine-rich oligonucleotides, when structured, manifest themselves by
      CD contributions around 260 or 295 nm. For instance, positive bands at 264 nm and
      295 nm, respectively, signal the parallel and antiparallel guanine quartets,
      while a positive band around 261 nm may indicate the presence of a (parallel?)
      Hoogsteen duplex. A positive band at 264 nm may also reflect the presence of
      rigidly and unusually oriented GpT and TpG steps within loops. The signatures are
      additive with those of other structural features of the same molecule, such as
      hairpins or Watson-Crick duplexes, whose bands are observed at 280 nm.

PMID- 11981848
TI  - Single-nucleotide polymorphism in repetitive sequences of the human deleted in
      azoospermia complex.
AB  - A simple and inexpensive single-nucleotide polymorphism (SNP) analysis procedure
      is described that uses the Fotodyne Analyst System equipped with the Gel-Pro
      Analysis software to compare the relative fluorescent intensity of ethidium
      bromide stained and MboI restricted amplicons from male individuals. The
      different intensity ratios reflect the ratio of repetitive elements with and
      without an MboI restriction enzyme site. The polymerase chain reaction (PCR)
      products represent a reiterated sequence within the Y-linked deleted in
      azoospermia (DAZ) complex involved in male fertility in humans. This procedure
      was utilized to determine the ratio of MboI(+) and MboI(-) repetitive sequences
      in 32 male individuals from two human populations, the Buryat from Mongolia and
      the Mayan from Yucatan. The proportion of wildtype to mutant amplicons was found
      to vary from 0 to 100% among individuals. This technique is well suited for large
      scale analysis of the locus investigated in this manuscript and other similar
      polymorphisms. This approach may contribute to the study of recent human
      evolution based on Y-chromosome analysis as well as medical and developmental
      issues concerning the significance of these repetitive elements in male
      infertility.

PMID- 11981849
TI  - Comparison of three DNA marker systems for assessing genetic diversity in Asian
      arowana (Scleropages formosus).
AB  - Three DNA marker systems -- random amplified polymorphic DNA (RAPD), amplified
      fragment length polymorphism (AFLP) and microsatellites -- were used to estimate
      the genetic diversity in Asian arowana (Scleropages formosus) by genotyping fish
      individuals from three different sources. Parallel application of the three DNA
      marker systems allowed us to compare their utility for the analysis of genetic
      diversity. Microsatellites displayed the highest expected heterozygosity, whereas
      the values obtained by RAPD and AFLP were much lower. Multiplex ratio and marker
      index were higher for AFLP than for RAPD or microsatellites. Weak correlation was
      detected between genetic similarity estimated from data obtained with the three
      DNA marker systems: estimates from RAPD and AFLP data turned out to be higher
      than those from microsatellites. On the other hand genetic similarity was higher
      in the red variety than in the green one, especially when tested with
      microsatellites. Based on the genetic distance matrices calculated from
      microsatellite analysis, all red individuals were clustered into one group,
      whereas only a subset of them was clustered when either RAPD or AFLP was used.
      This indicated that the microsatellite system detected population subdivision
      more efficiently than either RAPD or AFLP.

PMID- 11981850
TI  - Comparison of RNA, single-stranded DNA and double-stranded DNA behavior during
      capillary electrophoresis in semidilute polymer solutions.
AB  - We present a study of the separation of RNA, single-stranded DNA (ssDNA) and
      double-stranded DNA (dsDNA) in semidilute linear hydroxyethylcellulose (HEC)
      solution. Our results strive to provide a better understanding of the mechanisms
      of nucleic acid migration during electrophoresis in polymer solutions under
      native and denaturing conditions. From a study of the dependence of mobility on
      chain length and applied electric field, we found that RNA and ssDNA show better
      separation and higher resolution over a larger range of sizes compared to dsDNA.
      In addition, RNA reptation without orientation extends to longer chain lengths in
      comparison to ssDNA, possibly as a result of different type of short-lived
      secondary structure formations. Such a comparative study between nucleic acid
      capillary electrophoresis helps to optimize RNA separation and provides better
      understanding of RNA migration mechanisms in semidilute polymer solutions under
      denaturing conditions.

PMID- 11981851
TI  - On-line coupling of capillary isotachophoresis and zone electrophoresis for the
      assay of phenolic compounds in plant extracts.
AB  - The combination of capillary isotachophoresis (ITP) and capillary zone
      electrophoresis (CZE) in the column coupling configuration was optimized in a
      mode where the electrolyte for the CZE step is different from the leading and
      terminating ITP electrolytes. Two colored markers, picric acid and 1-nitroso-2
      naphthol, were used for exact timing of the transfer of isotachophoretically
      stacked analyte zones into the CZE column and for the control of the residual
      amount of the leading and terminating ITP electrolytes entering the CZE capillary
      together with the analytes, thus controlling the duration of transient ITP
      migration in the CZE capillary and ensuring good separation of the analytes and
      reproducibility of the migration times (relative standard deviations 1%). ITP-CZE
      was applied to the simultaneous assay of several cinnamic acid derivatives and
      flavonoids in methanolic extracts of Sambucus flowers and Crataegus leaves and
      flowers. The preconcentrating and cleansing effect of the ITP step allowed
      injection of relatively large sample volumes (30 microL). The limits of detection
      were approximately 20-50 ng x mL(-1) and 100 ng x mL(-1) for the acids and
      flavonoids, respectively ( thick similar 200-times lower compared to conventional
      CE) with spectrophotometric detection at 254 nm. The ITP-CZE exhibited
      satisfactory linearity and precision when using CZE buffer of pseudo "pH" 9.0; 1
      nitroso-2-naphthol was employed as the internal standard. The separation took
      approximately 35 min. The ITP-CZE results for rutin, hyperoside, and vitexin-2-O"
      rhamnoside were in good accordance with those obtained previously by high
      performance liquid chromatography.

PMID- 11981852
TI  - Separation and first structure elucidation of Cremophor EL-components by
      hyphenated capillary electrophoresis and delayed extraction-matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry.
AB  - The polyethoxylated heterogeneous components of the so far poorly characterized
      nonionic emulsifier Cremophor EL (polyoxyl 35 castor oil) (CrEL) were
      fractionated by cyclodextrin-modified micellar electrokinetic capillary
      chromatography (CD-MEKC). Due to the low UV absorbance of most of the CrEL
      components an indirect UV detection was used with phenobarbital-sodium as
      background absorber. For a precise assignment of the resulting peaks to the
      corresponding components capillary electrophoresis (CE) had to be combined with
      delayed extraction-matrix assisted laser desorption/ionization-time of flight
      mass spectrometry (DE-MALDI-TOF-MS) as detection system. For this purpose, the
      fractionating robot Probot was employed which enables both the on-line
      fractionation of the CE eluate on a MALDI target during the electrophoretic
      separation and the simultaneous dosage of the MALDI matrix solution. The applied
      CrEL amount was optimized by varying the CE injection parameters time, pressure
      and concentration of the sample in order to obtain homologue peak series of
      sufficient intensity without decreasing the separation efficiency. Evaluation of
      the mass spectra was performed by comparing the residue masses of the homologue
      peak series with the calculated residue masses of potential CrEL-components.
      However, the high number of polyethoxylated components leads to overlapping of
      homologue peak series with isobaric residue masses. These isobaric interferences
      were detected by a high mass accuracy of the measurements (obtained by internal
      calibration with polyethylene glycol (PEG) 1000 and by means of the residue mass
      plot, the newly developed evaluation method. The combination of these techniques
      allowed the first detailed structure analysis of the CrEL-components showing
      glycerol polyoxyethylene (POE) monoricinoleate and POE monoricinoleate to be the
      two main components of the emulsifier. Furthermore, the coupling of CE with DE
      MALDI-TOF-MS is generally applicable to the fractionation and identification of
      polymers.

PMID- 11981853
TI  - Determination of the kinetic parameters of rhodanese by electrophoretically
      mediated microanalysis in a partially filled capillary.
AB  - Electrophoretically mediated microanalysis (EMMA) was applied for the study of
      kinetic parameters of the bisubstrate enzymatic reaction of rhodanese. The
      Michaelis constants (K(m)) for both substrates and the effect of temperature on
      rhodanese reaction were evaluated by means of the combination of the EMMA
      methodology with a partial filling technique. In this setup, the part of the
      capillary is filled with the buffer best for the enzymatic reaction whereas, the
      rest of the capillary is filled with the background electrolyte optimal for
      separation of substrates and products. The enzymatic reaction was performed in 25
      mM N-(2-hydroxymethyl)piperazine-2'-(2-ethanesulfonic acid) (HEPES) buffer (pH
      8.5) while the low pH background electrolyte 100 mM beta-alanine-HCl (pH 3.5) was
      used for separation of substrates and products that are the inorganic anions. The
      estimated value of K(m) for thiosulfate of 1.30 x 10(-2) M was consistent with
      previously published values; the K(m) for cyanide of 7.6 x 10(-3) M was
      determined for the first time. In addition, the type of kinetic mechanism of
      enzymatic reaction was also elucidated. The finding of the double displacement
      (ping-pong) mechanism is in accordance with previous literature data. Also, the
      experimentally determined temperature optimum of the rhodanese-catalyzed reaction
      around 20-25 degrees C agreed with literature values.

PMID- 11981854
TI  - Adaption of a fragment analysis technique to an automated high-throughput
      multicapillary electrophoresis device for the precise qualitative and
      quantitative characterization of microbial communities.
AB  - The analysis of microbial communities is of increasing importance in life
      sciences and bioengineering. Traditional techniques of investigations like
      culture or cloning methods suffer from many disadvantages. They are unable to
      give a complete qualitative and quantitative view of the total amount of
      microorganisms themselves, their interactions among each other and with their
      environment. Obviously, the determination of static or dynamic balances among
      microorganisms is of fast growing interest. The generation of species specific
      and fluorescently labeled 16S ribosomal DNA (rDNA) fragments by the terminal
      restriction fragment length polymorphism (T-RFLP) technique is a suitable tool to
      overcome the problems other methods have. For the separation of these fragments
      polyacrylamide gel sequencers are preferred as compared to capillary sequencers
      using linear polymers until now because of their higher electrophoretic
      resolution and therefore sizing accuracy. But modern capillary sequencers,
      especially multicapillary sequencers, offer an advanced grade of automation and
      an increased throughput necessary for the investigation of complex communities in
      long-time studies. Therefore, we adapted a T-RFLP technique to an automated high
      throughput multicapillary electrophoresis device (ABI 3100 Genetic Analysis) with
      regard to a precise qualitative and quantitative characterization of microbial
      communities.

PMID- 11981855
TI  - Profiling and screening analysis of 27 aromatic amino acids by capillary
      electrophoresis in dual modes.
AB  - An efficient capillary electrophoretic (CE) profiling and screening system based
      on dual modes of capillary zone electrophoresis (CZE) and micellar electrokinetic
      capillary chromatography (MEKC) was developed for the simultaneous determination
      of 23 nonprotein amino acids (NPAAs) and 4 protein amino acids with aromatic
      moiety. It involves separation by an uncoated fused-silica capillary under
      phosphoric acid buffer in CZE mode and by another uncoated fused-silica capillary
      under neutral sodium dihydrogen phosphate buffer containing sodium dodecyl
      sulfate in MEKC mode. Migration orders of the amino acids studied on the two
      separation modes under each optimum condition were very different. The
      repeatability of migration times measured by the CZE and MEKC was found to be
      better than 4.8 and 3.4%, respectively, thereby enabling to cross-check the
      identification of each amino acid. The method linearity and limit of detection of
      the CZE for each amino acid were found to be adequate for the assay of aromatic
      amino acids. When the present CE profiling and screening analysis in dual modes
      was applied to plant seeds, NPAAs such as mimosine from Mimosa pudica Linne, and
      2-phenylglycine from Lindera erythrocarpa Makino were positively detected along
      with tryptophan, phenylalanine and tyrosine.

PMID- 11981856
TI  - Pyrenebutanoate as a dynamic protein modifier for fluorometric detection in
      capillary zone electrophoresis.
AB  - Pyrenebutanoate as the amphiphilic fluorescent compound is suggested as a buffer
      additive in capillary zone electrophoresis (CZE) for a dynamic modification of
      several protein samples. Using deuterium lamp UV excitation for the on-column
      fluorometric detection, minimum detectable amounts in the amol-range of the
      proteins sampled on the CZE capillary was achieved.

PMID- 11981857
TI  - Analytical potential of fluorescein analogues for ultrasensitive determinations
      of phosphorus-containing amino acid herbicides by micellar electrokinetic
      chromatography with laser-induced fluorescence detection.
AB  - The analytical potential of three fluorescein analogues, fluorescein
      isothiocyanate isomer I (FITC), 5-(4,6-dichlorotriazinylamino) fluorescein (DTAF)
      and 5(6)-carboxyfluorescein N-succinimidyl ester (CFSE), as labelling reagents
      for the ultrasensitive determination of phosphorus-containing amino acid
      herbicides (glufosinate and glyphosate) and aminomethylphosphonic acid (the major
      metabolite of glyphosate) by nonionic surfactant micellar electrokinetic
      chromatography (MEKC) with laser-induced fluorescence (LIF) detection was
      investigated. Practical aspects related to label chemistry and MEKC separation
      showed that DTAF is the best choice for the determination of these herbicides; in
      addition, the most important features of these reagents for the derivatization of
      amino compounds are discussed. The optimum procedure includes a derivatization
      step of the herbicides at 40 degrees C with DTAF for 1 h and a 2-fold dilution
      prior to MEKC analysis, which is conducted within about 10 min using Brij-35 in
      the running buffer. This nonionic surfactant improves the selectivity and
      therefore the sensitivity of the method at low analyte concentrations by shifting
      the interfering peaks of the DTAF excess. The lowest detectable analyte
      concentration ranged from 0.06 to 0.16 microg/L with a precision of 2.1-3.2%.
      These results indicate that nonionic surfactant MEKC-LIF is useful as a
      selective, rapid and sensitive tool for the determination of these herbicides
      showing a great potential for their analysis in environmental samples without
      previous enrichment steps. The proposed method surpasses other chromatographic
      alternatives in terms of limit of detection and sample requirements for the
      analysis.

PMID- 11981859
TI  - Capillary electrophoretic determination of apoptosis of rat cerebellar granule
      cells induced by 1-methyl-4-phenyl pyridium ion.
AB  - A capillary electrophoresis method for the direct detection of whole cell
      apoptosis is described. We successfully used this method to detect the apoptosis
      of rat cerebellar granule cells, induced by 1-methyl-4-phenyl pyridium ion
      (MPP(+)). The conditions for the detection were optimized: including the effects
      of running buffer pH, the voltage, and the ID of the capillaries. The effects of
      MPP(+) concentration and apoptosis time on the relative content of the apoptotic
      cells were studied. The relative standard deviations of the migration time and
      the absorbance of the apoptotic cells were found to be 10.8 and 8.6%,
      respectively. The results correlated well with those obtained by using the methyl
      green-pironin stained experiment and DNA agarose electrophoresis.

PMID- 11981858
TI  - Determination of twelve heparin- and heparan sulfate-derived disaccharides as 2
      aminoacridone derivatives by capillary zone electrophoresis using ultraviolet and
      laser-induced fluorescence detection.
AB  - In quest for high sensitivities, we developed an ultrahigh capillary
      electrophoresis (CE) method for the structural analysis of heparin and heparan
      sulfate (HS) in biologic samples. Heparin and HS were digested with an equi-unit
      mixture of heparin lyases I, II and III and the obtained Delta-disaccharides were
      derivatized with the fluorophore 2-aminoacridone. All known twelve non-, mono-,
      di- and trisulfated Delta-disaccharides were completely resolved in a single run,
      using 50 mM phosphate buffer, pH 3.5, and reversed polarity at 30 kV. Relative
      standard deviation in migration times and peak areas as well as day-to-day
      variance ranged from 0.9 to 2.4%, suggesting a reproducible and precise method.
      Detection of 2-aminoacridone (AMAC)-derivatives of Delta-disaccharides by UV at
      255 nm showed 2.8 and 10 times higher sensitivity than that of derivatized and
      non-derivatized ones at 232 nm. Laser-induced fluorescence detection with an Ar
      ion laser source showed an approximately 100 times higher sensitivity than that
      obtained at 232 nm of the non-derivatized species. Application of this method to
      quantitative analysis of Delta-disaccharides derived from porcine intestinal
      mucosa heparin and bovine kidney HS showed excellent agreement with previously
      published methods, suggesting an accurate method. The developed method can be
      easily applied for the disaccharide analysis of heparin/HS at the attomole level
      with high accuracy, for distinguishing between heparin and HS and may be of value
      for studying their interactions with matrix effective molecules.

PMID- 11981860
TI  - A silica monolithic column prepared by the sol-gel process for enantiomeric
      separation by capillary electrochromatography.
AB  - A method for the preparation of a silica monolithic capillary
      electrochromatography (CEC) column for the separation of enantiomers has been
      developed. The porous silica monolith was fabricated inside a fused-silica
      capillary column by using the sol-gel process. After gelation for 24 h,
      hydrothermal treatment at 100 degrees C for 24 h was performed to prevent the sol
      gel matrix from cracking. The prepared monolith was then coated with Chirasil
      beta-Dex which represents a chiral polymer prepared by grafting permethyl-beta
      cyclodextrin to polymethylsiloxane with an octamethylene spacer. Immobilization
      of Chirasil-beta-Dex was performed by heat treatment at 120 degrees C for 48 h to
      give a nonextractable coating. The column performance was evaluated by using
      racemic hexobarbital as a model compound. The efficiency of 9.2 x 10(4)
      theoretical plates/m for the first eluted enantiomer of hexobarbital was obtained
      at an optimal flow rate of the mobile phase. The effect of mobile phase
      composition on enantiomeric separation of hexobarbital was also investigated. The
      column proved to be stable for more than one hundreds of runs during a two-months
      period. The enantiomers of several neutral and negatively charged chiral
      compounds were baseline separated on this column.

PMID- 11981861
TI  - Chiral capillary electrophoretic determination of the enantiomeric purity of
      tetrahydronaphthalenic derivatives, melatoninergic ligands, using highly sulfated
      beta-cyclodextrins.
AB  - Using cyclodextrin capillary zone electrophoresis (CD-CZE), baseline separation
      of synthetic tetrahydronaphthalenic derivatives, potential melatoninergic
      compounds, was achieved. A method for the enantioresolution of these tetralins
      and determination of their enantiomeric purity was developed using anionic CDs
      (highly sulfated-CD or highly S-CD) as chiral selectors and capillaries
      dynamically coated with polyethylene oxide (PEO). Operational parameters such as
      the nature and concentration of the chiral selectors, buffer pH, organic
      modifiers, temperature and applied voltage were investigated. The use of charged
      CDs provides a driving force for our neutral compounds in the running buffer and
      enantiomeric resolution by inclusion of compounds in the CD cavity. The highly S
      beta-CD was found to be the most effective complexing agent, allowing good
      enantiomeric resolution. The complete resolution of three tetralin compounds was
      obtained using 25 mM phosphate buffer at pH 2.5 containing 2.5% w/v of highly S
      beta-CD at 25 degrees C with an applied field of 0.25 kV/cm. The apparent
      association constants of the inclusion complexes were calculated. This optimized
      method was validated in terms of linearity, sensitivity, accuracy and recovery.
      The enantiomeric purity for the three molecules was determined and the detection
      limit of enantiomer impurities is about 0.3-0.6%.

PMID- 11981862
TI  - Poly(dimethylsiloxane) microchip for precolumn reaction and micellar
      electrokinetic chromatography of biogenic amines.
AB  - We have demonstrated that precolumn derivatization and capillary electrophoresis
      separation on a poly(dimethylsiloxane) (PDMS) microchip can be realized as
      efficient as those on glass microchips. In an optimized condition of micellar
      electrokinetic chromatography (MEKC), using 25 mM sodium borate buffer (pH 10.0)
      with 25 mM sodium dodecyl sulfate (SDS) and 5% v/v methanol, the electroosmotic
      flow in an oxidized PDMS microchip is stabilized within 3% for days. By employing
      a fluorometric derivatization with o-phthaldialdehyde (OPA) in an optimally
      designed reaction chamber, four most important biogenic amines occurring in
      foods, histamine, tyramine, putrescine, and tryptamine, are quantitatively
      determined in less than 1 min at the levels applicable to real samples. The
      migration behaviors of anionic OPA-derivatized biogenic amines under the MEKC
      conditions are analyzed, and it has been found that under our separation
      conditions, the electrophoretic mobility of the SDS micelles is significantly
      greater than those of the anions in the aqueous phase. The channel manifold in a
      PDMS substrate is fabricated using replica molding against a thick photoresist,
      SU-8, pattern generated by photolithography. The plate with the microchannel
      pattern is strongly, irreversibly bonded to another PDMS plate by using a new
      bonding technique, which employs surface oxidation by corona discharge generated
      from a cheap, handy source, Tesla coil.

PMID- 11981863
TI  - A novel injection method for high-speed proteome analysis by capillary
      electrophoresis.
AB  - We have developed a new sample injection method for capillary electrophoresis
      (CE) that reduces the required migration time. We demonstrated a pressurization
      technique that was performed with buffer in the outlet after the electrokinetic
      sample injection with no buffer in the outlet. To reduce the migration time, the
      sample injection had to be performed with no buffer in the outlet; water should
      be pressurized while the buffer is in the outlet. Though the resolution was
      slightly decreased using this method, the addition of a separation carrier
      (curdlan) to the run buffer restored the resolution without delaying the
      migration time. The use of our new sample injection method combined with our high
      quality separation carrier will enable us to improve the efficiency of the high
      throughput screening (HTS) system for proteome analysis.

PMID- 11981864
TI  - Recombinant autofluorescent landmarks for standardization of electrophoretic
      migration of proteins.
AB  - Unequivocal identification of unknown protein spot patterns in two-dimensional (2
      D) electrophoresis still represents a major problem when performing comparative
      studies of different 2-D electrophoresis gels. Inhomogeneity of gels due to
      variations in the gel casting procedure, electroendoosmosis and heterogeneity of
      proteins are major contributions to variations in migration patterns. By fusing
      green fluorescent protein to a number of well-defined selected proteins (human
      lysozyme, initiation factor 5a (EIF5a), rapamycin-selective 25 kDa immunophilin
      (FKBP25), and heat shock protein 90 beta (hsp90)), the isoelectric points and the
      molecular mass were designed. Proteins were additionally tagged with the FLAG tag
      enabling rapid purification by immunoaffinity chromatography. The fusion proteins
      were expressed intracellularly in yeast to avoid heterogeneity caused by post
      translational modifications. The quality and applicability was tested in 1-D and
      2-D electrophoresis. Sharp bands or symmetric spots were obtained. The proteins
      are considered as a new generation of reference proteins for electrokinetic
      separation methods.

PMID- 11981865
TI  - Identification of low-abundance proteins of bovine colostral and mature milk
      using two-dimensional electrophoresis followed by microsequencing and mass
      spectrometry.
AB  - We identified several low-abundance proteins of bovine colostrum and mature milk
      using the immunoabsorption technique and two-dimensional electrophoresis (2-DE)
      followed by microsequencing and mass spectrometry. Two major milk proteins, beta
      casein and immunoglobulin G (IgG), were effectively removed from the milk using
      immunoabsorbents. Milk samples before and after immunoabsorption were separated
      by 2-DE. Protein identification of the spots on 2-DE was performed by either gel
      comparison, microsequencing, matrix-assisted laser desorption/ionization-time of
      flight mass-spectrometry (MALDI-TOF-MS), peptide mass fingerprinting or peptide
      sequencing using tandem MS by hybrid quadrupole/orthogonal acceleration time of
      flight-MS (Q-TOF). Significant differences in protein patterns were observed
      between the low-abundance proteins of colostrum and mature milk. In addition,
      several low-abundance proteins including fibrinogen beta-chain, chitinase 3-like
      1, alpha-antitrypsin, complement C3 alpha-chain, gelsolin and apolipoprotein H
      were observed only in colostrum. However, the level of beta-casein fragments
      increased significantly during this lactation period. alpha-Lactalbumin and beta
      lactoglobulin as well as some low-abundance proteins including bovine serum
      albumin, serotransferrin and lactoferrin were identified in both colostral and
      mature milk. Low-abundance proteins in bovine colostrum may have special
      physiologic relevance to the health and development of calves early in lactation.

PMID- 11981866
TI  - Identifying the major proteome components of Helicobacter pylori strain 26695.
AB  - The whole genome sequences of Helicobacter pylori strain 26695 have been
      reported. Whole cell proteins of H. pylori strain 26695 cells were obtained and
      analyzed by two-dimensional electrophoresis, using immobilized pH gradient
      strips. The most abundant proteins were shown in the region of pI 4.0-9.5 with
      molecular masses from 10 to 100 kDa. Soluble proteins were precipitated by the
      use of 0-80% saturated solutions of ammonium sulfate. Soluble proteins
      precipitated by the 0-40% saturations of ammonium sulfate produced similar spot
      profiles and their abundant protein spots had acidic pI regions. However, a
      number of soluble proteins precipitated by more than 60% saturation of ammonium
      sulfate were placed in the alkaline pI regions, compared to those precipitated by
      40% saturation. In addition, we have performed an extensive proteome analysis of
      the strain utilizing peptide MALDI-TOF-MS. Among the 345 protein spots processed,
      175 proteins were identified. The identified spots represented 137 genes. One
      hundred and fifteen proteins were newly identified in this study, including DNA
      polymerase III beta-subunit. These results might provide guidance for the
      enrichment of H. pylori proteins and contribute to construct a master protein map
      of H. pylori.

PMID- 11981867
TI  - Comparison of protein expression profiles between monolayer and spheroid cell
      culture of HT-29 cells revealed fragmentation of CK18 in three-dimensional cell
      culture.
AB  - The use of three-dimensional cell culture models, so-called multicellular tumor
      spheroids, is a special approach in experimental cancer research, because
      spheroids are similar to in vivo tumors in structural as well as functional
      sense. Cells grown in spheroids exhibit alterations of cell cycle regulation,
      induction of apoptosis and differentiation and can acquire multidrug resistance.
      In this study we investigated the protein expression in human colorectal cancer
      cells grown in monolayer and in spheroid cultures using proteomics. Evaluation by
      computer-assisted image analysis revealed overexpression of three cytokeratin 18
      fragments that were generated in vivo. Cytokeratin 18 has previously been
      described as a target for caspase-mediated cleavage during apoptosis and our
      results indicate that apoptosis may take place in spheroids. Other proteins
      upregulated in spheroids include calreticulin precursor, a rho GDP dissociation
      inhibitor variant, several cytokeratins and peroxiredoxin 4. Some of these
      proteins have already been linked to chemoresistance and apoptotic phenomena.

PMID- 11981868
TI  - Analysis of the human lumbar cerebrospinal fluid proteome.
AB  - Idiopathic low back pain has no known cause, and the molecular basis is unknown.
      Neuropeptidergic systems have been previously studied, and proteomics methods
      have been applied in this present study. Proteomics combines high-resolution two
      dimensional (2-D) gel electrophoresis, high-sensitivity mass spectrometry, and
      continuously expanding protein databases. Proteomics offers a comprehensive,
      bird's-eye view to analyze, at a systems level, all of the proteins in
      cerebrospinal fluid (CSF) that might contribute to idiopathic low back pain. CSF
      contains a high salt concentration and low protein concentration. In order to
      obtain a high-quality 2-D pattern, several sample preparation methods were tested
      to remove salts - protein precipitation with either acetone or trichloroacetic
      acid/acetone, or sample treatment with a Bio-Spin column. More spots were
      visualized on the 2-D gel of human CSF, and a relatively high protein recovery
      was obtained when a Bio-Spin column was used to process a human CSF sample. Sixty
      one protein spots, obtained from 2-D gels with a pH range of either 3-10 or 4-7,
      were identified by matrix assisted laser desorption/ionization-mass spectrometry
      (MALDI-MS) and MALDI-post-source decay (PSD)-MS. These 61 protein spots represent
      22 proteins; six of those proteins were not annotated in any previously published
      2-D maps. Those six proteins are PRO2619, pigment epithelium-derived factor,
      albumin homolog, kallikrein-6 precursor, DJ717I23.1, and AMBP protein precursor.
      These protein-mapping data will contribute to the database that will be used in
      the future to compare the proteomes obtained from the CSF of controls and low
      back pain patients, to characterize differentially expressed proteins, and to
      elucidate the biological markers for idiopathic low back pain.

PMID- 11981869
TI  - Identification of new proteins in follicular fluid of mature human follicles.
AB  - Proteins present in human follicular fluid (HFF) have been poorly characterized
      to date. The purpose of our study was to analyse the protein content and identify
      new proteins originating from fluid of mature human follicles. A total of six
      females from infertile couples referred for in vitro fertilization (IVF) were
      stimulated and 44 follicular fluid samples from mature follicles yielding an
      oocyte were collected 34-36 h after human chorionic gonadotropin administration.
      HFF samples were processed for high-resolution two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE). Comparative analysis of the 2-D gels revealed up to
      600 spots, of which four were selected because of variations in their expression
      level. Using direct sequencing procedures (Edman degradation) or matrix assisted
      laser desorption/ionization-mass spectrometry (MALDI-MS), these four spots were
      identified as three new proteins: thioredoxin peroxydase 1 (TDPX1), transthyretin
      (TTR) and retinol-binding protein (RBP). The proteins identified here may emerge
      as potential candidates for specific functions during folliculogenesis and may
      prove useful as biomedical markers for follicle and/or oocyte maturation.

PMID- 11981870
TI  - IgM are associated to Sp alpha (CD5 antigen-like).
AB  - In 1993, we reported the presence of an IgM-associated peptide (M(r) 44 kDa; pI
      5.45) in all immunoglobulin M (IgM) fractions purified from plasma/serum by
      various methods. This peptide was absent in Ig fractions of non-IgM isotypes. The
      N-terminal sequence was determined as being APPSGVRLVGGLH. To gain insight into
      the nature of this peptide, we further analyzed, using modern proteomic tools,
      the IgM-associated peptide isolated from cryoglobulins. Mass spectrometry
      revealed three peptides of different masses: 2203.13 (ELGCGAASGTPSGILYEPPAEK),
      1564.83 (KPIWLSQMSCSGR), and 1544.77 (EATLQDCPSGPWGK). Theses sequences together
      with the already known N-terminal sequence allowed us to identity the IgM
      associated peptide as Sp alpha (O43866 in TrEMBL database; CD5 antigen-like). Sp
      alpha is a member of the scavenger receptor cysteine-rich superfamily of
      proteins. This family includes the T-and B-cell antigens CD5 and CD6, and several
      of its members influence immune cell fate. Our finding may have important
      implications in the understanding of the homeostasis of IgM antibodies.

PMID- 11981872
TI  - Production of laccase as the sole phenoloxidase by a Brazilian strain of
      Pleurotus pulmonarius in solid state fermentation.
AB  - The production of laccase by a Brazilian strain of Pleurotus pulmonarius was
      studied in solid state fermentation using wheat bran as substrate. Among
      oxidative and hydrolytic enzymes tested (laccase, aryl alcohol oxidase, lignin
      peroxidase, Mn peroxidase, xylanase and cellulase), laccase was the main enzyme
      produced by P. pulmonarius. The most suitable condition for maximum production of
      laccase (8,600 U/g substrate) was initial moisture content of 75% and 5 days of
      cultivation at 30 degrees C. The optimum pH and temperature for laccase activity
      were found to be 6.5 and 50 degrees C, respectively. P. pulmonarius laccase was
      stable at 50 degrees C for more than 6 hours, and it retained about 73% and 18%
      of its activity when heated for 1 h at 55 and 60 degrees C, respectively. The
      enzyme was greatly stable at alkaline pH, but not at acidic pH. The laccase
      activity appear to be correlated with the ability of crude extract to decolourize
      several industrial dyes.

PMID- 11981873
TI  - The pab1 gene of Coprinus cinereus encodes a bifunctional protein for para
      aminobenzoic acid (PABA) synthesis: implications for the evolution of fused PABA
      synthases.
AB  - The pab1 gene of the basidiomycete Coprinus cinereus encodes PABA synthase,
      necessary for para-aminobenzoic acid production. The C. cinereus protein is
      bifunctional with an N-terminal glutamine amidotransferase domain and a C
      terminal chorismate amination domain. In most bacteria, these two functions are
      encoded in separate genes (e.g., pabA and pabB of E. coli). Fused PABA synthases
      have so far been detected in actinomycetes, Plasmodium falciparum, fungi and
      Arabidopsis thaliana. Phylogenetic analysis shows that the fused PAB sequences
      form a tight group that also includes uncharacterized PabB homologues from
      several bacteria. Unfused bacterial PabA proteins group with the glutamine
      amidotransferase subunits of bacterial anthranilate synthases, independent of
      organismal systematics, indicating a complex and perhaps independent evolutionary
      origin. In contrast, unfused PabB group and fused PabA/B proteins form a
      monophyletic group on a branch separate from the chorismate amination subunits of
      anthranilate synthases, probably reflecting a need for recognition of different
      positions in the common substrate chorismate.

PMID- 11981874
TI  - Toxicity of Bacillus thuringiensis and B. sphaericus to laboratory populations of
      Drosophila melanogaster (Diptera: Drosophilidae).
AB  - A total of 65 samples, consisting of 8 sample types, collected from the Jordan
      Valley, were examined for the presence of Bacillus thuringiensis and B.
      sphaericus and for their toxicity against the larvae of the fruit fly Drosophila
      melanogaster. The frequency of samples containing toxic aerobic spore-forming
      bacilli was 12%; of which 21.7% belonged to B. thuringiensis and 17.4% to B.
      sphaericus. The B. thuringiensis populations consisted of 5 serogroups:
      thuringiensis (H1), entomocidus (H6), pakistani (H13), autoagglunated, in
      addition to a new serotype. The B. sphaericus population consisted of 3
      serogroups, and belonged to serovars H5, H9, and H13. All B. thuringiensis and B.
      sphaericus local isolates, in addition to the reference strains B. thuringiensis
      kuristaki, and B. thuringiensis israelensis, showed high toxicity towards 3(rd)
      instar larvae of D. melanogaster. The toxic concentrations ranged between 2.0 x
      10(6) and 4.4 x 10(7) viable spores ml(-1).

PMID- 11981875
TI  - Intra-strain variability of Cryptococcus neoformans can be detected on phloxin B
      medium.
AB  - A method was devised for easy detection of intra-strain variability of the human
      pathogenic yeast Cryptococcus neoformans. Cultivation of strains on a medium
      containing Phloxin B resulted in different coloured colonies. Generally, colonies
      were either pink or red; however there were also several colony-colour segregant
      in which both colours could be observed. A number of these segregants were
      isolated and analysed. Virulence factors such as the cell and capsule sizes were
      measured; further temperature sensitivity, growth rates, mating-types and melanin
      production were also studied. Segregants were examined by random amplified
      polymorphic DNA (RAPD) fingerprinting and electrophoretic karyotyping by pulsed
      field gel electrophoresis (CHEF). They showed both phenotypic and genotypic
      differences. The main differences appeared in phenotypic characters and RAPD
      patterns; while the chromosomal patterns remained unchanged. Reversion frequency
      analysis revealed that the reason for this segregation could be due to phenotypic
      switching. The physiological reason for the colour changes was also investigated
      and was attributed to the differential ability of the cells to accumulate Phloxin
      B either into their capsules or into their cells. The method described here is
      potentially applicable for the detection of strain heterogeneity in both basic
      and clinical microbiology laboratories.

PMID- 11981876
TI  - Use of direct Gram stain of stomach biopsy as a rapid screening method for
      detection of Helicobacter pylori from peptic ulcer and gastritis patients.
AB  - Four hundred and thirty five stomach mucosal biopsies were taken from 145
      consecutive patients (3 from each patient) during investigations for dyspepsia in
      three hospitals in Western Nigeria. The aim was to determine the best suited
      rapid screening method to aid fast diagnosis of ulcer/gastritis in this
      environment, using Gram stain, CLO test kit (urease production test) and culture
      methods. Eighty-nine (61.4%) biopsies were positive using Gram stain, 61 (42.1%)
      using CLO test kit and only 28 (19.3%) using culture. Based on the various
      limitations of CLO test kits and culture methods, Gram stain was adjudged the
      best suited rapid method. The clinical implication of this finding is discussed.

PMID- 11981877
TI  - Characterization of JP-7 jet fuel degradation by the bacterium Nocardioides
      luteus strain BAFB.
AB  - In the fall of 1996, numerous bacteria capable of degrading JP-7 jet fuel were
      isolated from soil collected at Beale Air Force Base in northern California. The
      most prevalent organism, identified as Nocardioides luteus by16s rRNA sequencing
      (MIDI Labs, Inc.), was selected for further analysis. Analysis of JP-7 following
      inoculation with N. luteus demonstrated degradation of the C(11) alkane component
      of the fuel. Growth rates of N. luteus were determined with alkanes of various
      lengths as the sole carbon and energy source. The organism grew best on shorter
      length alkanes (C(8) and C(10)). Growth was measurably slower on C(11), and
      minimal on C(12), C(13), and C(14).

PMID- 11981878
TI  - New homoserine lipids from Xerocomus langbianensis.
AB  - New diacylglycerotrimethyl homoserine lipids 1 (2 O,3 O-bislinolylglycero-4'-O
      (N,N,N-trimethyl)homoserine) and 2 (2 O,3 O-linolyl-palmitylglycero-4'-O-(N,N,N
      trimethyl)-homoserine) were isolated from the fruiting body of a Vietnamese
      species of Xerocomus langbianensis. The chemical structures were settled on the
      basis of mass spectrometry and NMR spectroscopy.

PMID- 11981879
TI  - Molecular genotyping of isolates of Actinobacillus actinomycetemcomitans by
      pulsed-field gel electrophoresis after separate digestion with Sse8387I and XhoI.
AB  - Genomic DNA from 18 Japanese clinical isolates of Actinobacillus
      actinomycetemcomitans was obtained from six periodontitis patients and analyzed
      using pulsed-field gel electrophoresis (PFGE) after separate digestion with
      Sse8387I and with XhoI. Three isolates from an identical patient were found to
      share an identical PFGE profile, and isolates from distinct patients were found
      to have PFGE profiles distinctly different from each other. Consequently, the 18
      Japanese clinical isolates were discriminated into six distinct genotypes by
      means of PFGE. The genomic DNA from the other six reference strains (ATCC33384,
      ATCC43717, ATCC 43718, JCM2434, JCM2435 and Nig-1) was discriminated into six
      genotypes by the same PFGE methodology, and these six genotypes were found to be
      distinctly different from the six genotypes of the 18 Japanese clinical isolates
      described above. Serotyping demonstrated three PFGE genotypes in the serotype a
      strains, four the serotype b strains and three the serotype c strains. The
      present results clearly suggest that the PFGE procedure after separate digestion
      with Sse8387I and with XhoI has an excellent discriminatory power amongst strains
      and has a good genotypability for A. actinomycetemcomitans.

PMID- 11981881
TI  - Pharmacophore features of potential drugs.
AB  - Drug discovery efforts rely increasingly on the identification of quality lead
      compounds through high-throughput synthesis and screening. However, large-scale
      random libraries have yielded only a low number of quality lead molecules. To
      address this shortcoming researchers have paid more attention to the concept of
      "drug-likeness" of molecules in combinatorial and screening libraries. Database
      profiling and analysis methods have been employed to identify the structural
      features of known drug molecules. Neural networks and machine learning methods
      help to distinguish between drugs and nondrugs. More recently, database
      independent pharmacophore filters have been introduced that provide simple
      intuitive rules to classify potential drugs.

PMID- 11981882
TI  - Multivalent cyclooligosaccharides: versatile carbohydrate clusters with dual role
      as molecular receptors and lectin ligands.
AB  - Results obtained over the past decade towards the preparation of multitopic
      carbohydrate architectures combining the molecular inclusion capabilities of
      cyclomaltooligosaccharide receptors (cyclodextrins, CDs) and the recognition
      properties of saccharide ligands towards biological receptors are discussed. The
      potential of these new sugar-based "intelligent" transporters for site specific
      delivery of therapeutics is outlined.

PMID- 11981883
TI  - "Alkaline-earth metals in a box": structures of solvent-separated ion pairs.
AB  - During our research on homoleptic organocalcium compounds, we found that
      fluorenylcalcium complexes show unusual solution behavior and precipitate from
      nonpolar solvents after addition of THF. Their solid-state structures reveal the
      unexpected rupture of both metal-carbanion bonds by the polar solvent THF. The
      crystal structures of five new Mg and Ca solvent-separated ion pairs are
      described. The compound [Ca(2+)(thf)(6)][Me(3)Si(fluorenyl(-))](2) is the first
      organometallic complex of a Group 2 element that crystallizes as a completely
      solvent-separated ion pair. The driving forces for its formation are: 1) the
      strong Ca-THF bond; 2) the stability of the free [Me(3)Si(fluorenyl)](-) ion; 3)
      encapsulation of [Ca(2+)(thf)(6)] in a "box", the walls of which consist of
      anionic fluorenyl ligands and benzene molecules; and 4) the presence of numerous
      (THF)C- H...pi interactions. The magnesium analogue
      [Mg(2+)(thf)(6)][Me(3)Si(fluorenyl(-))](2) is isostructural. Bis(7,9
      diphenylcyclopenta[a]acenaphthadienyl)calcium also crystallizes as a completely
      solvent-separated ion pair and can likewise be described as a [Ca(2+)(thf)(6)]
      species in a box of delocalized anions and benzene molecules. In addition, the
      structures of two Ph(4)B(-) complexes of Mg and Ca are described.
      [Mg(2+)(thf)(6)][Ph(4)B(-)](2) crystallizes as a completely solvent-separated ion
      pair and also shows a solvated metal cation bonded via C-H.pi interactions in a
      cavity formed by Ph(4)B(-) ions. [(thf)(4)CaBr(+)][Ph(4)B(-)] has a structure in
      which one of the anionic ligands is still bonded to the Ca atom. Bridging bromide
      ligands result in the formation of the dimer [(thf)(4)CaBr(+)](2).

PMID- 11981884
TI  - Double elimination protocol for synthesis of 5,6,11,12
      tetradehydrodibenzo[a,e]cyclooctene.
AB  - A new method for constructing 5,6,11,12-tetradehydrodibenzo[a,e]cyclooctene is
      described on the basis of one-pot double elimination protocol. The target
      molecule, which is the smallest cyclophane with alternate arylene-ethynylene
      linkage, is synthesized in 61 % yield through oxidative dimerization of ortho
      (phenylsulfonylmethyl)benzaldehyde. The initial carbon-carbon bond formation
      between sp(3) carbons followed by stepwise conversion to sp(2) and finally sp
      carbons bypasses the difficulty encountered in direct coupling of the sp carbon
      in the terminal acetylene. The mechanism of this process is discussed. The Wittig
      Horner-type coupling is a key reaction employed for the carbon-carbon bond
      formation. Generation of (E)-vinylsulfone moiety in the first coupling between
      alpha-sulfonyl anion and aldehyde functions is crucial for the effective second
      coupling to complete the cyclization. The syn-elimination of the (E)-vinylsulfone
      moieties in the cyclized intermediate furnishes the acetylenic bonds.

PMID- 11981885
TI  - Sulfoximine version of double elimination protocol for synthesis of chiral
      acetylenic cyclophanes.
AB  - A new strategy for constructing enantiopure acetylenic cyclophanes is described
      on the basis of one-pot double elimination reaction starting from dialdehydes and
      bis(sulfoximine)s. In this case, the conventional sulfone protocol affords poorer
      yields of the desired cyclophanes. Thus, arylene-ethynylene moieties with
      terminal sulfoximine or formyl functions are linked to binaphthyl cores and these
      building blocks are then subjected to double elimination reaction. The desired
      macrocycles are obtained in up to 35 % yield. The corresponding Sonogashira
      coupling fails to afford cyclophanes indicative of effectiveness of the double
      elimination methodology.

PMID- 11981886
TI  - Synthesis and NaOTf mediated self-assembly of monodendritic crown ethers.
AB  - The synthesis of ten benzyl ether based self-assembling monodendrons containing
      benzo[15]crown-5 at their focal point is presented. These dendritic building
      blocks self-assemble either directly or via complexation with NaOTf in two
      dimensional smectic B, smectic A, and p6mm hexagonal columnar (Phi(h)) and three
      dimensional Pm3n cubic lattices. Retrostructural analysis of these lattices and
      of the lattices generated from the same monodendrons containing various other
      functional groups at their focal point by X-ray diffraction experiments provided
      for the first time a correlation between the molecular structure and the shape of
      the monodendron, the shape of the supramolecular dendrimer and the symmetry of
      the lattice. It has been shown that complexation with NaOTf provides the
      following five different trends: a) stabilization of the three-dimensional Pm3n
      cubic lattice self-organized from spherical dendrimers that are self-assembled
      from conic monodendrons; b) stabilization of the two-dimensional S(A) phase
      generated from parallel-piped monodendrons; c) no effect on the stability of the
      two-dimensional S(B) phase generated from parallel-piped monodendrons; d)
      stabilization of the two-dimensional p6mm hexagonal columnar phase self-organized
      from cylindrical supramolecular dendrimers that are self-assembled from tapered
      monodendrons; and e) destabilization of the two-dimensional p6mm hexagonal
      columnar phase self-organized from cylindrical supramolecular dendrimers self
      assembled from half-disc monodendrons. Mechanisms of NaOTf mediated self-assembly
      processes were suggested. These monodendritic crown ethers and their NaOTf
      complexes provide the largest diversity of liquid crystalline phases encountered
      so far in any library of supramolecular dendrimers.

PMID- 11981887
TI  - Constructing terbium co-ordination polymers of 4,4'-bipyridine-N,N'-dioxide by
      means of diffusion solvent mixtures.
AB  - Five different co-ordination polymers of terbium(III) and the bidentate ligand
      4,4'-bipyridine-N,N'-dioxide (L), [Tb(L)(CH(3)OH)(NO(3))(3)](infinity) (1),
      ([Tb(L)(1.5)(NO(3))(3)].CH(2)Cl(2))(infinity) (2),
      ([Tb(L)(1.5)(NO(3))(3)].CH(3)OH.0.8H(2)O)(infinity) (3),
      ([Tb(L)(1.5)(NO(3))(3)].0.4C(2)Cl(4).0.8CH(3)OH)(infinity) (4), and
      [Tb(L)(2)(NO(3))(3)](infinity) (5) have been synthesised by the use of different
      "diffusion solvent mixtures", and structurally characterised by X-ray
      crystallography. Compound 1, with a Tb:L stoichiometry of 1:1, adopts a zig-zag
      chain structure, which forms three-fold interpenetrating diamondoid frameworks
      through interchain hydrogen bonding between co-ordinated methanol and a nitrate
      group on an adjacent chain. Polymers 2, 3, and 4 all have a Tb:L stoichiometry of
      1:1.5, but adopt different topologies. For 2, a ladder arrangement is found and
      large channels which accommodate solvent CH(2)Cl(2) molecules are formed by
      superposition of the ladders. For 3 and 4 4.8(2) net structures are observed. The
      superposition of the 4.8(2) nets in 3 and 4, by disposing adjacent layers such
      that every octagon is positioned below a tetragon from the neighbouring layer,
      allows the formation of two kinds of channel, with that inside the tetragons
      accommodating methanol molecules. The other kind of channel, between tetragons,
      accommodates water molecules in the case of 3 and tetrachloroethylene molecules
      in the case of 4. Compound 5, with a Tb:L stoichiometry of 1:2, has a linear
      polymeric structure with one bridging and one terminal ligand, and forms (6,3)
      plane nets by means of intermolecular electrostatic interactions between N-oxide
      moieties. X-ray powder diffraction studies show that upon desolvation, compound 2
      maintains its original ladder framework.

PMID- 11981888
TI  - Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives
      through anionic benzyne cyclization.
AB  - The development of a new method for the regioselective synthesis of
      functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is
      reported. The key step involves the generation of a benzyne-tethered vinyl or
      aryllithium compound that undergoes a subsequent intramolecular anionic
      cyclization. Reaction of the organolithium intermediates with selected
      electrophiles allows the preparation of a wide variety of indole,
      tetrahydrocarbazole, dihydrofenantridine, dibenzopyran, and dibenzothiopyran
      derivatives. Finally, the application of this strategy to the appropriate
      starting materials allows the preparation of some tryptamine and serotonin
      analogues.

PMID- 11981889
TI  - Through-space spin-spin coupling in van der Waals dimers and CH/pi interacting
      systems. An ab initio and DFT study.
AB  - The through-space J(HH) and J(CH) spin-spin coupling constants of model van der
      Waals dimers (involving methane, ethylene, and benzene), and of selected
      compounds showing the CH/pi interaction, have been investigated by means of DFT
      and ab initio calculations. In the range of intermolecular separations for which
      the interaction is stabilizing, weak couplings (0.1-0.3 Hz) are predicted for
      J(CH), while the corresponding J(HH) couplings are much smaller. The relative
      contributions (Fermi-contact, spin-orbit, and spin-dipole) are strongly dependent
      on the geometry of the dimers and on the distance; the non-negligible values of
      J(CH) for pi systems stem largely from an incomplete cancellation of spin-orbit
      terms. The results obtained for the larger molecules, that is,
      acetonitrile@calix[4]arene 5, the imine 6, and the aryl ester 7 are consistent
      with those on the model dimers. For 7, the occurrence of a through-space
      mechanism for the transmission of coupling is established by examining trends in
      the magnitude of couplings as a function of the number of intervening covalent
      bonds.

PMID- 11981890
TI  - Reactions of Group 8, 9, and 10 monocations (Fe+, Co+, Ni+, Ru+, Rh+, Pd+, Os+,
      Ir+, Pt+) with phosphane in the gas phase.
AB  - The reactions of Group 8, 9 and 10 monocations with phosphane were studied under
      single-collision conditions in a Fourier transform ion cyclotron resonance (FT
      ICR) mass spectrometer. Fe(+) is completely unreactive, Co(+) reacts slowly and
      shows both adduct formation and P-H bond activation, and Ni(+) reacts slowly as
      well but shows adduct formation only. In contrast to their first-row congeners,
      the investigated second- and third-row transition metal monocations show facile P
      H bond activations. Remarkably, extensive dehydrogenations of the collision
      complexes yield cations MPH(+), MP(2) (+), MP(3)H(+), MP(4) (+) and so on.
      Exceptional behaviour is shown by the two d(9) cations palladium (whose
      "dehydrogenation power" is rather limited) and platinum (which gives rise to a
      great manifold of only partially dehydrogenated species as well). Collision
      induced dissociation experiments suggest that P(2) and PH units are formed as
      ligands.

PMID- 11981891
TI  - Isolation of an oxomanganese(V) porphyrin intermediate in the reaction of a
      manganese(III) porphyrin complex and H2O2 in aqueous solution.
AB  - The reaction of [Mn(TF(4)TMAP)](CF(3)SO(3))(5) (TF(4)TMAP=meso-tetrakis(2,3,5,6
      tetrafluoro-N,N,N-trimethyl-4-aniliniumyl)porphinato dianion) with H(2)O(2) (2
      equiv) at pH 10.5 and 0 degrees C yielded an oxomanganese(V) porphyrin complex 1
      in aqueous solution, whereas an oxomanganese(IV) porphyrin complex 2 was
      generated in the reactions of tert-alkyl hydroperoxides such as tert-butyl
      hydroperoxide and 2-methyl-1-phenyl-2-propyl hydroperoxide. Complex 1 was capable
      of epoxidizing olefins and exchanging its oxygen with H(2) (18)O, whereas 2 did
      not epoxidize olefins. From the reactions of [Mn(TF(4)TMAP)](5+) with various
      oxidants in the pH range 3-11, the O-O bond cleavage of hydroperoxides was found
      to be sensitive to the hydroperoxide substituent and the pH of the reaction
      solution. Whereas the O-O bond of hydroperoxides containing an electron-donating
      tert-alkyl group is cleaved homolytically, an electron-withdrawing substituent
      such as an acyl group in m-chloroperoxybenzoic acid (m-CPBA) facilitates O-O bond
      heterolysis. The mechanism of the O-O bond cleavage of H(2)O(2) depends on the pH
      of the reaction solution: O-O bond homolysis prevails at low pH and O-O bond
      heterolysis becomes a predominant pathway at high pH. The effect of pH on (18)O
      incorporation from H(2) (18)O into oxygenated products was examined over a wide
      pH range, by carrying out the epoxidation of carbamazepine (CBZ) with
      [Mn(TF(4)TMAP)](5+) and KHSO(5) in buffered H(2) (18)O solutions. A high
      proportion of (18)O was incorporated into the CBZ-10,11-oxide product at all pH
      values but this proportion was not affected significantly by the pH of the
      reaction solution.

PMID- 11981892
TI  - Alkali and alkaline-earth-metalated forms of calix[4]arenes: synthons in the
      synthesis of transition metal complexes.
AB  - This is the first coherent report on the metalation of calix[4]arene by alkali
      and alkaline-earth metals, thus providing a high-yield production of appropriate
      synthons for the synthesis of transition metal calix[4]arenes. In addition,
      various facets of the coordination chemistry by calix[4]arene anions of alkali
      and alkaline-earth metal ions have been singled out. Among them: 1) the exo and
      endo coordination of metal ions by the calix[4]arene skeleton; 2) the pi
      solvation of the ions by the phenyl rings; 3) the ion-carrier properties of
      metallacalix[4]arenes; 4) the simulation of the kinetically labile coordination
      sphere of alkali and alkaline-earth metal ions by a polyoxo rigid skeleton. The
      peculiarities of the complexation of alkali and alkaline-earth metal ions by
      calix[4]arenes outlined are deduced from the synthesis and the structural
      characterization both in solution ((1)H NMR) and in the solid state (X-ray
      structure analysis) of the following classes of compounds: 1) [p-tBu
      calix[4](OMS(n))(4)](2) (M=Li, Na, K); 2) [p-tBu-calix[4](OR)(2)(O)(2)ML] (M=Mg,
      L=THF, R=C(5)H(9); M=Ca, L=TMEDA (tetramethylethylenediamine), R=C(5)H(9); M=Ca,
      L=DME (dimethoxyethane), R=C(5)H(9); M=Ba, L=TMEDA, R=C(5)H(9); M=Ba, L=none,
      R=C(5)H(9)); 3) [p-tBu-calix[4](OC(5)H(9))(2)(O)(2)Ca(2)I(2)(MeCN)(2)]; 4) [(p
      tBu-calix[4](OR)(2)(O)(2))(2)BaNa(2)].

PMID- 11981893
TI  - Solvent-dependent mixed complex formation-NMR studies and asymmetric addition
      reactions of lithioacetonitrile to benzaldehyde mediated by chiral lithium
      amides.
AB  - Lithioacetonitrile and a chiral lithium amide with an internally coordinating
      methoxy group form mixed dimers in diethyl ether (DEE) and in tetrahydrofuran
      (THF) according to NMR studies. Based on the observed (6)Li,(1)H heteronuclear
      Overhauser effects, in THF lithioacetonitrile is present in a mixed complex with
      the chiral lithium amide, and this complex has a central N-Li-N-Li core. In DEE,
      on the other hand, the acetonitrile anion bridges two lithiums of the dimer to
      form a central six-membered Li-N-C-C-Li-N ring. Gauge individual atomic orbital
      DFT calculations of the (13)C NMR chemical shifts of the DEE- and THF-solvated
      mixed dimers show good agreement with those obtained experimentally.
      Lithioacetonitrile complexed to the chiral lithium amide has been employed in
      asymmetric addition to benzaldehyde in both DEE and THF. In THF the product, (S)
      3-phenyl-3-hydroxy propionitrile, is formed in 55 % ee and in DEE the R
      enantiomer is formed in 45 % ee. This change in stereoselectivity between
      solutions in DEE and THF was found to be general among a number of different
      chiral lithium amides, all with an internal chelating methoxy group.

PMID- 11981894
TI  - Silver phosphanes partnered with carborane monoanions: synthesis, structures and
      use as highly active Lewis acid catalysts in a hetero-Diels-Alder reaction.
AB  - Four Lewis acidic silver phosphane complexes partnered with [1-closo
      CB(11)H(12)](-) and [1-closo-CB(11)H(6)Br(6)](-) have been synthesised and
      studied by solution NMR and solid-state X-ray diffraction techniques. In the
      complex [Ag(PPh(3))(CB(11)H(12))] (1), the silver is coordinated with the
      carborane by two stronger 3c-2e B-H-Ag bonds, one weaker B-H-Ag interaction and a
      very weak Ag.C(arene) contact in the solid state. In solution, the carborane
      remains closely connected with the [Ag(PPh(3))](+) fragment, as evidenced by
      (11)B chemical shifts. Complex 2 [Ag(PPh(3))(2)(CB(11)H(12))](2) adopts a dimeric
      motif in the solid state, each carborane bridging two Ag centres. In solution at
      low temperature, two distinct complexes are observed that are suggested to be
      monomeric [Ag(PPh(3))(2)][CB(11)H(12)] and dimeric
      [Ag(PPh(3))(2)(CB(11)H(12))](2). With the more weakly coordinating anion
      [CB(11)H(6)Br(6)](-) and one phosphane, complex 3 [Ag(PPh(3))(CB(11)H(6)Br(6))]
      is isolated. Complex 4, [Ag(PPh(3))(2)(CB(11)H(6)Br(6))], has been characterised
      spectroscopically. All of the complexes have been assessed as Lewis acids in the
      hetero-Diels-Alder reaction of N-benzylideneaniline with Danishefsky's diene.
      Exceptionally low catalyst loadings for this Lewis acid catalysed reaction are
      required (0.1 mol %) coupled with turnover frequencies of 4000 h(-1)
      (quantitative conversion to product after 15 minutes using 3 at room
      temperature). Moreover, the reaction does not occur in rigorously dry solvent as
      addition of a substoichiometric amount of water (50 mol %) is necessary for
      turnover of the catalyst. It is suggested that a Lewis assisted Bronsted acid is
      formed between the water and the silver. The effect of changing the counterion to
      [BF(4)](-), [OTf](-) and [ClO(4)](-) has also been studied. Significant decreases
      in reaction rate and final product yield are observed on changing the anion from
      [CB(11)H(6)Br(6)](-), thus demonstrating the utility of weakly coordinating
      carborane anions in organic synthesis.

PMID- 11981895
TI  - On the existence of CuI pairs in ZSM-5--a computational study.
AB  - The siting and coordination of Cu(I) pairs in zeolite ZSM-5 have been studied by
      means of a combined quantum mechanics/interatomic potential function technique
      (QM-Pot). It couples a density functional theory (DFT) description employing a
      hybrid functional (B3LYP) for copper ions, including their local environment,
      with a DFT-parameterized shell model ion-pair potential for the periodic ZSM-5
      structure. A missing Cu(I)-Cu(I) interaction potential term in the force field
      has been parameterized on the basis of DFT results. Several distinct coordination
      sites for Cu(I) pairs have been identified within the ZSM-5 framework. These have
      been classified as open, nest, open-nest, and cage pairs, owing to the shape of
      their local environment in the crystal. A nest-shaped, bridged eight-membered
      ring constitutes the most probable site for the existence of Cu(I) ion pairs. It
      is energetically favored over all isolated Cu(I) sites. The excitation and
      emission energies for the singlet-triplet transition of the Cu(I) pairs have been
      studied. Earlier assignment of an emission band at 520 nm to Cu(I) pairs by
      others is not supported by our computed results.

PMID- 11981896
TI  - Stereoselective synthesis of structurally simplified cephalostatin analogues by
      multiple Heck reactions and their biological evaluation.
AB  - The stereoselective synthesis of structurally simplified heptacyclic
      cephalostatin analogues 2, 3, 18-21, 31, 32 and 33 by multiple Heck reactions is
      described. The key step of the synthesis is a selective Heck reaction of
      hydrindene 7 with 12 and 25, respectively at the vinyl bromide moiety followed by
      the introduction of a second molecule of 7 and a twofold intramolecular Heck
      reaction. The obtained bissteroidal heptacyclic compounds 2 and 3, in which the
      central octahydrophenazine moiety of 1 is replaced by a benzene ring, contain an
      unusual cis-annulation of the two newly generated rings. The cytotoxicity of some
      of the derivatives was determined on human lung cancer cell line A 549 in HTFCA
      tests (Human tumor colony forming ability). They show a rather high activity with
      an ED(50) in the micro molar range.

PMID- 11981897
TI  - The mechanism of 1,2-addition of disilene and silene: hydrogen halide addition.
AB  - The mechanism of 1,2-addition reactions of HF and HCl to Si=Si, Si=C, and C=C
      bonds has been investigated by ab initio quantum chemical methods. Geometries and
      relative energies of the stationary points and all the transition states were
      determined by using the MP2/6-311++G(d,p), B3LYP/6-311++G(d,p), and CBS-Q levels
      of theory. The investigated reactions can be characterized by two main
      thermodynamic profiles. The type in which the reagent molecule attacks a carbon
      atom is moderately exothermic with a high activation barrier. The second type in
      which a hydrogen halide attacks a silicon is strongly exothermic with a low
      activation energy. At the early stage of all the reactions a weakly bonded
      initial complex is found which indicates that the initial step of all the
      reactions is an electrophilic attack of hydrogen halide. The geometry and charge
      distribution of the transition state of the reactions indicate two main types of
      mechanism. If silicon is attacked, the halogen-silicon bond formation precedes
      the H-Y bond breaking. If, however, carbon is attacked, the first step is always
      an ionic dissociation of the hydrogen halide and a carbenium ion formation, which
      is stabilized by the C-Y bond formation in the final step of the reaction. The
      reaction diagrams and proposed mechanisms explain the experimentally found
      regioselectivity well.

PMID- 11981898
TI  - Revealing structural effects: electrochemical reactions of butanols on platinum.
AB  - Spectroelectrochemical studies on the reactivity of butanol isomers on Pt
      electrodes in perchloric acid medium led to the observation of structural effects
      that result from the different arrangements of atoms in the organic molecules.
      The use of differential electrochemical mass spectrometry (DEMS) to detect
      volatile products showed that all four isomers react on the electrode, though
      different product yields were observed for each compound. In spite of the
      differences in the electrochemical behaviour of the butanol isomers, a series of
      general processes accounts for the results obtained. The formation of strongly
      adsorbed residues by a dehydration process leading to the formation of a C=C bond
      was proposed for all isomers. Electroreduction of the adsorbates produces C(4)
      and C(3) alkanes, and the latter reveal the existence of a fragmentation process.
      The C(4) hydrocarbons can be formed by hydrogenation of these residues and by
      hydrogenolysis of alcohol molecules in the bulk solution which react at the
      electrode with adsorbed hydrogen. On the other hand, CO(2) is formed during
      electrooxidation of the adsorbed species. Partial-oxidation products containing a
      carbonyl group were detected from 0.2 M solutions of 1-butanol, isobutyl alcohol
      and sec-butyl alcohol. The tertiary alcohol tert-butyl alcohol only reacts in its
      adsorbed state.

PMID- 11981899
TI  - Gel-like lyomesophases formed in organic solvents by self-assembled guanine
      ribbons.
AB  - Lipophilic guanosine derivatives are self-assembled into ribbonlike aggregates,
      both in the crystal state and in solution. The structure of the ribbons has been
      characterised by single-crystal X-ray diffraction and, in solution, by NMR
      spectroscopy and ESI-MS. Two different ribbons with different patterns of
      hydrogen bonds are present in the solid state and in chloroform solutions. The
      gel-like phases obtained in hexadecane, toluene and chloroform have been
      investigated by optical microscopy and small-angle X-ray diffraction: the type of
      phase observed is related to the molecular structure of the compounds and depends
      dramatically on the solvent. The structures of the phases are discussed, with the
      presence of the two different ribbons being taken into account.

PMID- 11981900
TI  - Disulfide- and thiol-incorporating copper catenanes: synthesis, deposition onto
      gold, and surface studies.
AB  - Two new copper-complexed [2]catenanes have been prepared, both of which consist
      of two different interlocking rings. In both cases, one of the rings incorporates
      a disulfide bridge. The other ring contains either a single chelate (phen=1,10
      phenanthroline, a bidentate ligand) or two different chelates (phen and terpy,
      2,2',6',2"-terpyridine, a tridentate chelate). Deposition of these two complexes
      on a gold electrode surface was carried out by standard procedures, leading to
      reductive cleavage of the S-S bridge. The adsorbed species can be viewed as
      [2]catenanes for which the gold atoms of the electrode surface are an integral
      fragment of one of the two rings. They yield clear electrochemical responses, but
      no motion is observed for the catenane incorporating a phen unit and a terpy
      fragment in one of the two rings, regardless of the metal oxidation state. This
      is at odds with the behavior of the parent compound in solution, which undergoes
      ring-gliding motions upon electrochemical reduction or oxidation of the copper
      center. Near-field microscopy was used to study the deposited layers (STM and
      AFM). STM images suggest that the molecules do not tend to order at long range on
      the surface. Polarization modulation-infrared reflection absorption spectroscopy
      (PM-IRRAS) led to promising results: the two catenanes deposited are likely to be
      oriented perpendicular to the gold surface. Supporting information for this
      article is available on the WWW under http://www.wiley
      vch.de/contents/jc_2111/2002/f3636_s.pdf or from the author. 1: Infrared spectra
      of [Cu.2]+ as a powder (black line, transmission IR spectroscopy) and as a SAM on
      gold (dotted line, PM-IRRAS). (Spectra offset and scaled for clarity; significant
      peaks marked with an asterisk.) 2: STM image (819x819 nm2) of a monolayer of
      [Cu.3]+ on Au(111) on mica.

PMID- 11981901
TI  - Time-resolved resonance Raman spectroscopy and density functional study of 2
      fluorenylnitrene and its dehydroazepine products.
AB  - We report time-resolved resonance Raman spectra for 2-fluorenylnitrene and its
      dehydroazepine products acquired after photolysis of 2-fluorenylnitrene in
      acetonitrile. The experimental Raman band frequencies exhibit good agreement with
      the calculated vibrational frequencies from UBPW91/cc-PVDZ density functional
      calculations for the singlet and triplet states of the 2-fluorenylnitrene as well
      as BPW91/cc-PVDZ calculations for the two dehydroazepine ring-expansion product
      species. The decay of the 2-fluorenylnitrene Raman signal and the appearance of
      the dehydroazepine products suggest the presence of an intermediate species
      (probably an azirine) that does not absorb very much at the 416 nm probe
      wavelength used in the time-resolved resonance Raman experiments. Comparison of
      the singlet 2-fluorenylnitrene species with the singlet 2-fluorenylnitrenium ion
      species indicates that protonation of the nitrene to give the nitrenium ion leads
      to a significant enhancement of the cyclohexadienyl character of the phenyl rings
      without much change of the C-N bond length.

PMID- 11981902
TI  - Synthesis and photochemical behavior of phosphorus dendrimers containing
      azobenzene units within the branches and/or on the surface.
AB  - We describe the synthesis of three series of phosphorus-containing dendrimers
      having azobenzene derivatives specifically placed at some generations in the
      interior and/or on the surface. The largest compound obtained possesses 48
      azobenzene groups on the surface. Irradiation at 350 nm induces isomerization of
      the azobenzene groups from the E form to the Z form, whatever their location. The
      thermal back-isomerization to the E form in the dark at room temperature was
      observed in all cases. The kinetics of this Z-->E back-isomerization was studied
      in several cases; the rate is not dependent on the number of azobenzene units or
      of the generation, when the azobenzene groups are linked to the surface of the
      dendrimer. A different behavior was observed when the azobenzene groups were
      located within the framework of the dendrimer.

PMID- 11981903
TI  - Relative reactivities of carbonyl and thiocarbonyl groups toward
      dimethoxycarbene: two new dimethoxythiiranes.
AB  - Reaction of dimethoxycarbene (DMC), generated by thermolysis of a 2,5-dihydro
      1,3,4-oxadiazole, with 2,2,4,4-tetramethyl-3-thioxocyclobutanone afforded
      primarily 2,2-dimethoxy-3,3,5,5-tetramethyl-4-thioxocyclopentanone from ring
      expansion by overall insertion into the C-CO bond. 4,4-Dimethoxy-2,2,5,5
      tetramethyl-3-thioxocyclopentanone, from overall insertion into a C-CS bond, was
      a minor product. Thus the carbene had reacted preferentially at the carbonyl
      group, rather than the thiocarbonyl group of the four-membered ring. However, the
      minor product reacted with DMC at the thiocarbonyl group to afford a
      dimethoxythiirane. A product from a corresponding reaction at the carbonyl group
      could not be found. A rationale for the apparent reversal of relative
      reactivities of the carbonyl and thiocarbonyl groups is offered, with supporting
      evidence.

PMID- 11981904
TI  - 1,3-Diphospholene-4-ylidene chromium (tungsten) pentacarbonyl complexes formed by
      CO insertion into the ring of a 1,3-diphosphacyclobutane-2,4-diyl-2-ide-complexes
      of a phosphanyl carbene or a phosphonium ylide?
AB  - Reaction of the 1,3-diphosphacyclobutane-2,4-diyl-2-ide 1 with chromium or
      tungsten hexacarbonyl afforded the anionic complexes [cyclo-[P(Mes*)-C(SiMe(3))
      P(Mes*)-C(O)-C[M(CO)(5)]]](-) (3 a,b: M=Cr, W) by the formal insertion of CO into
      the four membered ring. Computational analysis suggests that this reaction
      proceeds via two intermediates that can be formulated as a cyclic metal acyl and
      an acyclic ketenyl complex. The anionic complexes 3 a,b further reacted with
      electrophiles to afford the neutral complexes [cyclo-(P(Mes*)-C(SiMe(3))-P(Mes*)
      C(OR)-C[M(CO)(5)])] (4 a,b: M=Cr, W, R=Me; 5, 6: M=Cr, R=SiMe(3), H). All
      products were characterized by standard spectroscopic (NMR and MS) techniques,
      and 4 a,b further by extensive one- and two-dimensional multinuclear ((1)H,
      (13)C, (31)P, (183)W) NMR studies. From these investigations, an unequivocal
      assignment of chemical shifts and coupling constants was derived, confirming
      unusually large shielding for the formal carbenic carbon atoms which exceed even
      those in complexes of imidazoyl carbenes. Single-crystal X-ray diffraction
      analyses of 3 a, 4 a,b, and 5 revealed that all of these compounds contain planar
      P(2)C(3) rings. The phosphorus atoms are slightly pyramidal, and the carbon-metal
      distances (C-Cr 218 pm, C-W 230 pm) suggest low bond orders. Comparison of the
      structural parameters of 3 a with those of the O-substitution products 4 a, 5
      revealed substantial changes in endocyclic P-C bond lengths and the degree of
      pyramidal character of bonding at the phosphorus atoms. In line with the
      spectroscopic and computational results, these effects were interpreted in terms
      of a considerable reorganization of pi electrons in the ring, which induces a
      substantial degree of aromatic character in the neutral complexes 4-6.

PMID- 11981905
TI  - An extraction-based assay for neutral anionophores: the measurement of high
      binding constants to steroidal receptors in a nonpolar solvent.
AB  - The extraction-based protocol for measuring binding constants, developed by Cram
      and co-workers, has been extended for use with anionic substrates. The method is
      especially useful for high-affinity receptors, allowing very high binding
      constants to be measured in nonpolar solvents. Distribution constants K(d)
      between chloroform and water have been obtained for tetraethylammonium chloride
      and bromide, thus calibrating the method for these two substrates. Application to
      steroidal podands 5-9 has confirmed the ability of electron-withdrawing groups to
      enhance hydrogen-bond donor capabilities. Binding constants of approximately 3 x
      10(7) M(-1) have been measured for the most powerful receptor 7. An X-ray crystal
      structure of 15, the methyl ester analogue of 7, reveals a well-defined binding
      site preorganised for anion recognition.

PMID- 11981907
TI  - Obstetrical ultrasound--today and tomorrow.

PMID- 11981908
TI  - Diagnosis of cardiac defects: where we've been, where we are and where we're
      going.
AB  - There has been tremendous development in the field of prenatal diagnosis of
      cardiac disease in the last 30 years. Early work centered on the technical
      aspects of providing an accurate assessment of cardiac structure and function.
      Techniques of fetal cardiac screening have been developed and utilized throughout
      the world. More recently, investigators have begun to explore the ramifications
      of fetal cardiac diagnosis by assessing measures of outcome. In this article, the
      field of fetal echocardiography, as a screening tool for identifying congenital
      heart disease, and its impact on disease outcome is reviewed.

PMID- 11981909
TI  - Ultrasound in prenatal diagnosis: polemics around routine ultrasound screening
      for second trimester fetal malformations.
AB  - Ultrasound for routine fetal malformation screening has been polemical from its
      early beginning because of the very broad range of diagnosis rates disclosed,
      i.e. from 13% to 82%, average 27.5%. A review of available studies is proposed to
      assess objectively the efficacy of ultrasound, considering also economical,
      ethical and methodological aspects as influential factors for choosing a routine
      screening policy. The utility of fetal malformation diagnosis before birth is
      brought forward, including second opinion, karyotyping, poly-disciplinary case
      discussion prior to management. Method and material of reviewed studies
      considerably vary and might influence the sensitivity results, as the choice of
      the population sample and selection of pregnant women, gestation age at
      screening, distribution of malformation among systems or tracts, exclusion of
      some fetal malformation and the routine practice of autopsy. Efficiency of
      screening studies is compared, and among them Radius and Eurofetus studies.
      Average sensitivity is finally considered as satisfactory in the daily practice
      when operated by trained personnel. The importance of additional factors for
      successful screening are emphasized such as education, equipment quality and
      fetal ultrasound examination at different gestation age for a better
      understanding of natural history of fetal morphology.

PMID- 11981910
TI  - Second trimester ultrasound screening for chromosomal abnormalities.
AB  - The use of prenatal ultrasound has proven efficacious for the prenatal diagnosis
      of chromosomal abnormalities. The first sonographic sign of Down syndrome, the
      thickened nuchal fold, was first described in 1985. Since that time, multiple
      sonographically-identified markers have been described as associated with Down
      syndrome. The genetic sonogram, involving a detailed search for sonographic signs
      of aneuploidy, can be used to both identify fetuses at high risk for aneuploidy
      and, when normal, can be used to decrease the risk for aneuploidy for a pregnancy
      when no sonographic markers are identified. Combining the genetic sonogram with
      maternal serum screening may be the best method of assessing aneuploidy risk for
      women who desire such an assessment in the second trimester. Trisomy 18, Trisomy
      13, and triploidy are typically associated with sonographically identified
      abnormalities and have a high prenatal detection rate. The use of the described
      sonographic signs in low-risk women requires further investigation, however,
      patients at increased risk for aneuploidy due to advanced maternal age or
      abnormal serum screening can benefit from a genetic sonogram screening for
      sonographic signs of aneuploidy to adjust their baseline risk of an affected
      fetus.

PMID- 11981911
TI  - Increased fetal nuchal translucency at 11-14 weeks.
AB  - Nuchal translucency (NT) is the sonographic appearance of a subcutaneous
      collection of fluid behind the fetal neck. The measurement of fetal NT thickness
      at the 11-14-week scan has been combined with maternal age to provide an
      effective method of screening for trisomy 21; for an invasive testing rate of 5%,
      about 75% of trisomic pregnancies can be identified. When maternal serum free
      beta human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma
      protein-A (PAPP-A) at 11-14 weeks are also taken into account, the detection rate
      of chromosomal defects is about 90%. Increased NT can also identify a high
      proportion of other chromosomal abnormalities and is associated with major
      defects of the heart and great arteries, and a wide range of skeletal dysplasias
      and genetic syndromes. In monochorionic twins, discordancy for increased NT is an
      early marker of twin-to-twin transfusion syndrome (TTTS). As with the
      introduction of any new technology into routine clinical practice, it is
      essential that those undertaking the 11-14-week scan are adequately trained and
      their results are subjected to rigorous audit.

PMID- 11981912
TI  - Ultrasound diagnosis of structural abnormalities in the first trimester.
AB  - The advances in ultrasound technology have made it possible to identify fetal
      structural abnormalities and genetic syndromes in the first trimester. First
      trimester prenatal diagnosis of fetal central nervous system, renal,
      gastrointestinal, cardiac, and skeletal abnormalities is reviewed.

PMID- 11981913
TI  - Sonography of fetal cerebrospinal anomalies.
AB  - Congenital anomalies of the central nervous system (CNS) are among the most
      frequent malformations. Current ultrasound equipment can give a precise diagnosis
      of many of these lesions from early gestation. High-resolution transvaginal
      probes play a major role both in allowing an early diagnosis and for better
      defining subtle details of both normal and abnormal cerebral anatomy. The
      diagnostic accuracy of prenatal ultrasound is, however, heavily dependent upon
      the expertise of the sonologist, the type of equipment employed, and the time
      dedicated to the scan. Fetal sonography is effective in identifying neural tube
      defects, although alpha-fetoprotein screening seems to give a greater
      sensitivity. The accuracy of ultrasound in the identification of CNS
      malformations other than neural tube defects remains unclear because of the
      ascertainment biases of the few large prospective studies that have been
      conducted to date.

PMID- 11981914
TI  - Intrauterine growth restriction (IUGR): biometric and Doppler assessment.
AB  - Intrauterine growth restriction (IUGR) is a common complication in pregnancy and
      influences morbidity and mortality at all stages of life. Historically, the
      management of IUGR has been dependent on antenatal biophysical testing and
      umbilical artery Doppler studies. With recent Doppler studies of the fetal
      central circulation, including intracardiac flows and the ductus venosus, better
      timing of delivery to minimize morbidity may be possible. This review will
      provide the reader with tools to diagnose IUGR, more accurately date the IUGR
      pregnancy with poor dating criteria, and better assess the condition of the IUGR
      fetus. A brief review of animal models of IUGR is presented to demonstrate
      research directions for answering human clinical questions and potentially
      carrying therapeutic intervention from the bench to the bedside.

PMID- 11981915
TI  - Current awareness in prenatal diagnosis.

PMID- 11981928
TI  - Comparison of sonography and MRI for diagnosing epicondylitis.
AB  - PURPOSE: The aim of this prospective study was to compare the sensitivity and
      specificity of sonography with those of MRI in evaluating epicondylitis. METHODS:
      The affected elbows of 11 patients with suspected epicondylitis were examined
      sonographically, and the contralateral (normal) elbow was also examined for
      comparison. In 10 of these patients, the affected elbow was also examined with
      MRI. In addition, both elbows of 6 volunteers without epicondylitis were examined
      sonographically; 1 elbow of each volunteer was designated as the "test" elbow and
      was examined with MRI. The sonograms of the patients' affected elbows and the
      volunteers' test elbows were paired with the sonograms of the contralateral
      elbows for comparison and were randomly shown twice to 2 readers. These readers,
      working independently and without knowledge of the findings of MRI, were
      instructed to state whether each elbow was normal or affected by epicondylitis.
      The MRI scans were then shown to the readers for similar review. RESULTS:
      Sonographic features of epicondylitis included outward bowing of the common
      tendon, presence of hypoechoic fluid subadjacent to the common tendon,
      thickening, decreased echogenicity, and ill-defined margins of the common tendon.
      Sensitivity for detecting epicondylitis ranged from 64% to 82% for sonography and
      from 90% to 100% for MRI. Specificity ranged from 67% to 100% for sonography and
      from 83% to 100% for MRI. CONCLUSIONS: Sonography is as specific but not as
      sensitive as MRI for evaluating epicondylitis. Used as an initial imaging tool,
      sonography might be adequate for diagnosing this condition in many patients, thus
      allowing MRI to be reserved for patients with symptoms whose sonographic findings
      are normal.

PMID- 11981929
TI  - Detection and differential diagnosis of hepatic masses using pulse inversion
      harmonic imaging during the liver-specific late phase of contrast enhancement
      with Levovist.
AB  - PURPOSE: The purpose of this study was to investigate whether late-phase pulse
      inversion harmonic imaging (PIHI) increases conspicuity in hepatic masses, helps
      to differentiate benign from malignant lesions, and demonstrates a greater number
      of and smaller metastatic lesions than do conventional (fundamental) sonography
      and helical CT. METHODS: Thirty patients (17 women and 13 men; age range, 35-77
      years; mean age, 54 years) with known or suspected liver masses were evaluated
      using both fundamental sonography and contrast-enhanced PIHI during the liver
      specific late phase of Levovist. The patients also underwent contrast-enhanced
      triphasic helical CT examinations within 1 week after sonography. In 4 of the
      patients, gadolinium-enhanced MRI was also performed as a part of their clinical
      work-up. RESULTS: The increase in the lesions' conspicuity on PIHI compared with
      fundamental sonography was significantly greater in malignant lesions than in
      benign lesions (p< 0.001). An echogenic rim was observed on PIHI in 8 (53%) of 15
      malignant lesions. The mean number of metastatic lesions visualized on PIHI (5.5
      +/- 5.3) was significantly higher than the mean number visualized on fundamental
      sonography (2.5 +/- 2.1, p < 0.05). Although lesions as small as 3 mm were
      observed on PIHI, the mean sizes of the smallest lesions demonstrated using
      fundamental sonography, PIHI, and helical CT were not significantly different.
      CONCLUSIONS: Late-phase PIHI is a useful technique for characterizing hepatic
      lesions and demonstrating both a greater number of and smaller metastases. It may
      help to differentiate benign from malignant liver masses and may obviate
      unnecessary and expensive further imaging.

PMID- 11981930
TI  - Clinical efficacy of prostate cancer detection using power doppler imaging in
      American and Japanese men.
AB  - PURPOSE: The aim of this study was to compare the detection rates of tumor
      vascular flow as measured by power Doppler imaging (PDI) in 2 populations and to
      determine whether PDI can reduce the number of unnecessary prostate biopsies in
      men with serum prostate-specific antigen (PSA) concentrations less than 10.1
      ng/ml. METHODS: The patient populations were Japanese (group 1) and American
      (group 2) men with either serum PSA concentrations of 4.1-10.0 ng/ml or abnormal
      findings on digital rectal examination (DRE) plus PSA concentrations less than
      4.1 ng/ml. We compared the overall diagnostic accuracy of DRE, gray-scale
      transrectal sonography (TRUS), and PDI between the 2 groups. RESULTS: In total,
      275 men were studied, 154 in group 1 and 121 in group 2. Cancer was identified in
      27% of men in group 1 and in 60% of group 2. Men with cancer in both groups
      differed significantly in age, peripheral zone volume, and mean number of
      positive biopsy cores. The sensitivity and specificity of PDI in group 2 were
      significantly inferior to those in group 1. The negative predictive value (NPV)
      of PDI was significantly higher for group 1 than for group 2. The NPV of PDI in
      group 1 was equivalent to that for the combination of DRE and TRUS, whereas the
      NPV for PDI in group 2 was significantly inferior to that of DRE and TRUS.
      CONCLUSIONS: Tumor vascularity could be detected by PDI more effectively in
      Japanese men with cancer than in American men with cancer. We hypothesize that
      this difference was a result of larger cancer volumes and smaller prostates in
      the Japanese men. PDI did not provide any performance advantage over DRE and TRUS
      in avoiding unnecessary biopsies.

PMID- 11981931
TI  - Color Doppler imaging in the sonohysterographic diagnosis of residual
      trophoblastic tissue.
AB  - PURPOSE: The purpose of this study was to evaluate the role of color Doppler
      imaging during sonohysterography in the diagnosis of residual trophoblastic
      tissue. METHODS: This prospective cohort study involved 25 consecutive women with
      clinical and sonographic signs of an echogenic intrauterine mass who were
      referred to the sonography unit of our institution for evaluation. All women
      underwent saline infusion sonohysterography with color Doppler sonographic
      evaluation. An operative hysteroscopy with histologic examination was performed
      in 17 cases. RESULTS: Thirteen women (group A) had sonohysterographic features
      suggestive of residual trophoblastic tissue (ie, an echogenic intrauterine lesion
      not detached from the uterine wall after introduction of saline). The initial
      diagnosis was confirmed by histologic analysis in all cases. Blood flow was
      detected within the intrauterine mass in 6 (46%) of these 13 women; the
      resistance indices were low in all 6 cases (mean +/- standard error, 0.38 +/-
      0.01). Twelve women (group B) had sonohysterographic findings negative for
      retained tissue, and no blood flow was detected within any of the intrauterine
      masses in this group (p < 0.05). CONCLUSIONS: Our results confirm the potential
      role of color Doppler sonography in the initial diagnosis of residual
      trophoblastic tissue. The detection of color Doppler signals, especially with low
      resistance flow, within an intrauterine lesion should increase the confidence of
      the sonologist in the diagnosis of residual trophoblastic tissue.

PMID- 11981932
TI  - Determination of thyroid volume by Sonography in healthy Brazilian
      schoolchildren.
AB  - PURPOSE: Our objective was to establish thyroid volume by sonography in Brazilian
      schoolchildren and to correlate thyroid volume with anthropometric
      characteristics. METHODS: Sonographic studies of thyroid volume were conducted in
      1,977 schoolchildren (6-14 years old) from 21 villages and towns in Central
      Brazil. Iodine concentration was analyzed in urine specimens and in salt samples
      obtained from the children's homes. Thyroid volumes were also compared with
      volumes reported for other countries. RESULTS: Age, height, and weight correlated
      with thyroid volume. Thyroid volumes for boys and girls were generally lower than
      those obtained in Europe and comparable to those obtained in Malaysia and Iran.
      Urinary iodine excretion was considered elevated in about half of the Brazilian
      schoolchildren, and the iodine content of salt samples was more than 50 ppm in
      58%. CONCLUSIONS: We observed relatively smaller thyroid gland volumes in
      Brazilian schoolchildren as compared with those reported in Europe. This was
      apparently due to a higher iodine intake in our population.

PMID- 11981933
TI  - Sonographically guided removal of a double J ureteral stent in an infant.
AB  - A 2-month-old male infant with a prenatally diagnosed obstruction of the
      ureteropelvic junction underwent a dismembered Anderson-Hynes pyeloplasty. A
      transanastomotic double J ureteral stent was placed between the renal pelvis and
      the urinary bladder. This report describes the subsequent removal of the double J
      ureteral stent from the patient's urinary bladder without the aid of a
      cystoscope: a rigid biopsy forceps was introduced trans-urethrally into the
      urinary bladder, and the stent was removed with sonographic guidance. Removal of
      a ureteral stent with sonographic guidance has not been previously reported in
      infants. This technique may be particularly useful in developing countries, where
      appropriate-sized cystoscopes and accessories may not be available.

PMID- 11981934
TI  - Sonographic findings in glomus tympanicum tumor.
AB  - A glomus tympanicum tumor that is associated with a visible retrotympanic mass is
      the most frequent cause of pulsatile tinnitus. The preoperative diagnostic
      approach to this lesion includes a meticulous physical examination as well as
      high-resolution CT, magnetic resonance angiography, and digital angiography,
      which can also be used for preoperative embolization. We report the use of color
      transcranial Doppler sonography in the evaluation of glomus tympanicum tumor in a
      67-year-old woman with a 3-year history of left tinnitus. An otoscopic
      examination revealed a reddish pulsatile mass behind an intact tympanic membrane.
      No lesions were visualized on gray-scale sonography. Contrast-enhanced color
      transcranial Doppler sonography showed a vascular ovoid mass that measured 2 x 1
      x 1 cm; spectral analysis of the lesion revealed arterial flow with a low
      resistance index. Color transcranial Doppler sonography helped define the
      dimensions and vascular characteristics of the lesion.

PMID- 11981935
TI  - Sonographic evaluation of a uterine angiolipoleiomyoma.
AB  - We report the case of a 51-year-old postmenopausal woman with an
      angiolipoleiomyoma, a rare mesenchymal uterine tumor, and describe its
      sonographic appearance. The clinical presentation of these invariably benign
      tumors often mimics that of uterine leiomyomas, making angiolipoleiomyomas
      difficult to diagnose correctly before histopathologic evaluation. In this case,
      sonography performed to determine the cause of the patient's vaginal bleeding
      showed a sharply marginated, brightly echogenic solid mass adjacent to the
      echogenic endometrium, without associated shadowing. Histopathologic examination
      revealed that this tumor was composed of smooth muscle, adipose tissue, fibrous
      connective tissue, and blood vessels. These sonographic findings, which are
      unusual for tumors of the uterus, suggest the diagnosis of angiolipoleiomyoma.
      Accurate diagnosis of these benign tumors could prevent patients from undergoing
      surgery and would allow appropriate counseling of patients.

PMID- 11981936
TI  - Endoanal sonography in the assessment of perianal endometriosis with external
      anal sphincter involvement.
AB  - Endoanal sonography can be used in the assessment of benign and malignant anal
      conditions and to evaluate the anatomy of the anal sphincters. We used endoanal
      sonography with a 10-MHz rotating endocavitary probe to evaluate a 45-year-old
      woman with a perianal mass, fecal incontinence, and menses-associated perianal
      pain. She had had 2 vaginal deliveries requiring episiotomies. Biopsy of the mass
      showed endometrial tissue. The ultrasound examination showed a perianal mass and
      an external anal sphincter injury. A wide excision and sphincteroplasty were
      performed, with improvement of fecal continence and pain. Histopathologic
      examination of the mass confirmed perianal endometrioma in an episiotomy scar.

PMID- 11981937
TI  - Diagnosis of an intracranial arteriovenous malformation using extracranial
      carotid Doppler sonography.
AB  - Carotid sonography is a well-established technique in the evaluation of patients
      with neurologic symptoms. We describe the case of a woman in whom duplex Doppler
      sonography of the extracranial carotid circulation showed high-velocity diastolic
      flow and a low resistance index without turbulence or morphologic abnormality of
      the artery. A suspected cause of this finding was low-resistance distal
      circulation secondary to low-resistance intracranial circulation due to an
      arteriovenous malformation. This diagnosis was later confirmed by CT. Because of
      the significant risk of bleeding associated with an asymptomatic intracranial
      arteriovenous malformation, duplex Doppler sonographic findings suggesting a low
      resistance waveform in the presence of a morphologically normal carotid artery
      should prompt further imaging.

PMID- 11981938
TI  - Inflamed urachal cyst containing calculi in an adult.
AB  - The urachus is an embryonic structure that persists after birth in some
      individuals and can cause various problems. We report a case of an inflamed
      urachal cyst filled with a thick yellow fluid and several calculi in a woman with
      a 1-month history of dysuria. Physical examination revealed a fist-sized tumor
      located infraumbically in the midline. The patient's erythrocyte sedimentation
      rate was elevated; the results of all other routine laboratory studies were
      normal. Sonography showed a regularly shaped, ovoid, hypoechoic cystic area in
      the abdominal wall measuring 8 x 4 x 3 cm and containing several hyperechoic
      masses associated with acoustic shadowing. The wall of the cyst was
      inhomogeneous, and a thin hypoechoic linear tract linked the superior aspect of
      the mass to the umbilicus. The results of excretory urography, voiding
      cystography, and cystoscopy excluded an abnormality of the urinary system. A
      urachal cyst was diagnosed, and the mass was surgically removed. The surgical
      specimen was sent for histopathologic analysis, which confirmed the diagnosis.

PMID- 11981939
TI  - Parliament calls for organised cervical cancer screening and HPV research.

PMID- 11981940
TI  - Pharmacology. Paper alert.

PMID- 11981941
TI  - Academy of Dental Materials Founders Award.

PMID- 11981942
TI  - Leiomyosarcoma versus myofibrosarcoma.

PMID- 11981943
TI  - Gastrointestinal autonomic nerve tumor in the colon.

PMID- 11981944
TI  - Gastrointestinal autonomic nerve tumor.

PMID- 11981945
TI  - [Retrocaval ureter].

PMID- 11981946
TI  - [Melanotic progonoma].

PMID- 11981947
TI  - Abstracts of the 8th Biennial Meeting of the International Society for Applied
      Cardiovascular Biology. February 27-March 2, 220. St Gallen, Switzerland.

PMID- 11981948
TI  - Abstracts of the 15th International Conference on Antiviral Research. Prague,
      Czech Republic, March 17-21, 2002.

PMID- 11981950
TI  - Wireless capsule video-endoscopy: an odyssey beyond the end of the scope.

PMID- 11981951
TI  - Protecting the innocent.

PMID- 11981952
TI  - Viral mutants and fulminant hepatitis. A dominant hepatitis B virus population
      defective in virus secretion because of several S-gene mutations from a patient
      with fulminant hepatitis.

PMID- 11981953
TI  - Viral mutants and fulminant hepatitis. Extraesophageal associations of
      gastroesophageal reflux disease in children without neurologic defects.

PMID- 11981954
TI  - Guided self-management and patient-directed follow-up of ulcerative colitis: a
      randomised trial.

PMID- 11981955
TI  - Becoming a statistic.

PMID- 11981956
TI  - Application of CEC procedures for the analysis of synthetic peptides:
      characterization of linear immunogenic peptides that mimic a HIV-1 gp120 epitope.
AB  - In this study, we describe the application of a new analytical procedure based on
      capillary electrochromatographic(CEC) techniques for the characterization of
      different basic and acidic peptides using isocratic eluent conditions containing
      acetonitrile and ammonium acetate buffers of different molarities between pH 3.8
      and 5.2. In particular,10 immunogenic peptide analogs with isoelectric points
      ranging from 3.7 to 10.1 were investigated; nine of these peptides, 1-9, were
      truncated analogs of the parent peptide, 10, which is a peptidomimetic related to
      a HIV-1 gp120 epitope. Several of these peptides have the propensity to form
      alpha-helical secondary structures in solution. Electrochromatographic
      separations of these peptides were achieved with packed fused silica
      capillaries(25 cm packed length, 100 microm i.d.) containing 3 microm n
      octadecylsilica particles. The influence of temperature on the CEC elution
      behavior of these peptides, as well as the impact of changes in the eluent
      composition, e.g. pH, buffer concentration and acetonitrile content, were
      examined. The results confirm that improvements in the resolution and analysis of
      synthetic peptides by CEC procedures result from the increase inelectroosmotic
      flow (EOF) as the temperature is increased. These findings emphasize the dominant
      influence of the temperature-dependent viscosity parameter, eta, on the EOF and
      thus on peptide resolution in CEC. Moreover, these investigations have shown that
      eluent properties can be specifically chosen to favor either electrophoretic
      mobility or chromatographic retention, with the overall CEC selectivity peptides
      of different sequence or composition reflecting the summated contributions from
      both separation mechanisms. Over the pH range 4.0-5.0, and using eluents with
      ionic strengths ranging from 6.2 to 15 mM ammonium acetate but containing a fixed
      volume fraction, psi, of acetonitrile above psi = 0.40, the CEC retention
      behavior of peptides 1-10 correlated with a linear relationship linking the
      retention coefficient, kappta(cec), and the differential frictional size-to-mass
      ratio parameter, Xi(fric), of these peptides. However, using eluents with a low
      acetonitrile content and low pH values, linear correlations were also observed
      between the incremental retention coefficient, Delta(Kappa)cec, and the product
      term [-0.66(Delta(Sigma[Xn]) log(Mi/Mj)], which links the difference in intrinsic
      hydrophobicities and molecular masses of two peptides, Pi and Pj. This study thus
      demonstrates the power of CEC procedures in the analysis of synthetic bioactive
      peptides and provides a general experimental framework to evaluate,using CEC
      procedures, the influence of the key molecular attributes of peptides on their
      structure-retention dependencies.Finally, these studies provide additional,
      practical insights into the use of CEC procedures for the analysis, resolution
      and biophysical characterization of closely related peptide analogs derived from
      solid-state peptide synthesis under conditions of different eluent composition or
      temperature.

PMID- 11981957
TI  - Throat culture tips.

PMID- 11981958
TI  - Postictal period procedures.

PMID- 11981959
TI  - Reducing errors with PYXIS.

PMID- 11981960
TI  - ViroLogic announces agreement with Achillion.

PMID- 11981961
TI  - Bibliography. Current world literature. Sexually transmitted diseases and urinary
      tract infections.

PMID- 11981963
TI  - Bibliography. Current world literature. Skin and soft tissue infections.

PMID- 11981962
TI  - Bibliography. Current world literature. HIV infection and AIDS.

PMID- 11981964
TI  - Bibliography. Current world literature. Respiratory infections.

PMID- 11981966
TI  - Bibliography. Current world literature. Paediatric and neonatal infections.

PMID- 11981965
TI  - Bibliography. Current world literature. Pathogenesis and immune response.

PMID- 11981967
TI  - Abstracts of the 22nd European Workshop for Rheumatology Research. Leiden, The
      Netherlands, 28 February-3 March 2002.

PMID- 11981968
TI  - The physiology of Campylobacter species and its relevance to their role as
      foodborne pathogens.
AB  - Campylobacter jejuni and C. coli are recognised as the leading causes of
      bacterial foodborne diarrhoeal disease throughout the development world. While
      most foodborne bacterial pathogens are considered to be relatively robust
      organisms, as a consequence of the necessity to survive the inimical conditions
      imposed by food processing and preservation, Campylobacter species have uniquely
      fastidious growth requirements and an unusual sensitivity to environmental
      stress. Campylobacters also lack many of the well characterised adaptive
      responses that can be collated with resistance to stress in other bacteria. The
      aim of this review is to outline the unusual physiology of campylobacters (C.
      jejuni and C. coli) and to describe how this influences their role as foodborne
      pathogens.

PMID- 11981969
TI  - The importance of RpoS in the survival of bacteria through food processing.
AB  - The resistance of bacteria to environmental stresses is recognised as an
      increasingly important area of microbiology. In particular, the alternative sigma
      factor RpoS has been shown to produce greater stress resistance in stationary
      phase cells of Salmonella and Escherichia coli compared with those in exponential
      phase. Our work has shown that RpoS can be induced in exponential phase in
      response to a number of inimical processes used in the food industry, including
      changes in water activity produced using a range of humectants and preservatives.
      The presence of high levels of competitor cells will also lead to early induction
      of RpoS in Salmonella by an as yet unknown mechanism. High levels of competitor
      cells also provide Salmonella with an increased resistance to heat and freeze
      thaw injury; the mechanism for this, however, is rpoS independent and has lead to
      the theory of a holistic mechanism for sub-lethal injury in respiring bacteria-
      the bacterial suicide response. This hypothesis predicts that sub-lethal injury
      occurs through the production of free radical species and not by the action of
      the applied inimical process per se. The demonstration of the production of a
      free radical burst when cells are subjected to differing types of stresses has
      been shown by a number of methods.

PMID- 11981970
TI  - Clostridium perfringens and foodborne infections.
AB  - Clostridium perfringens type A food poisoning is one of the more common in the
      industrialised world. This bacterium is also responsible for the rare but severe
      food borne necrotic enteritis. C. perfringens enterotoxin (CPE) has been shown to
      be the virulence factor responsible for causing the symptoms of C. perfringens
      type A food poisoning. CPE is a single polypeptide chain with a molecular weight
      of 3.5 kDa that binds to receptors on the target epithelial cells. Through a
      unique four-step membrane action it finally causes a breakdown in normal plasma
      membrane permeability properties. Genetic studies of cpe have shown that cpe can
      be either chromosomal or plasmid-borne and that only a small minority of the
      global C. perfringens population is cpe positive. CPE expression appears to be
      transcriptionally regulated during sporulation, at least in part, by regulatory
      factors that are common to all C. perfringens isolates.

PMID- 11981971
TI  - Osmoregulation and its importance to food-borne microorganisms.
AB  - The control of water activity has been used as a means of preserving foods for
      thousands of years. This preservation strategy presents food-borne microorganisms
      with serious problems, many of which relate to the management of water flow.
      Although the specific details of how each organism deals with these problems are
      different, several common themes have emerged. Bacteria induce specific
      responses. both physiological and genetic, to respond to either the loss or the
      gain of water, triggered by changes in the osmolarity of the environment. Many of
      the key systems have now been identified and the mechanisms of their regulation
      are beginning to be understood. Here we review recent developments in the field
      of bacterial osmoregulation with emphasis on key food-borne genera.

PMID- 11981972
TI  - A bacteriophage reagent for Salmonella: molecular studies on Felix 01.
AB  - Felix 01 (F01) is a bacteriophage originally isolated by Felix and Callow which
      lyses almost all Salmonella strains and has been widely used as a diagnostic test
      for this genus. Molecular information about this phage is entirely lacking. In
      the present study, the DNA of the phage was found to be a double-stranded linear
      molecule of about 80 kb. 11.5 kb has been sequenced and in this region A + T
      content is 60%. There are relatively few restriction endonuclease cleavage sites
      in the native genome and clones show this is due to their absence rather than
      modification. A restriction map of the genome has been constructed. The ends of
      the molecule cannot be ligated although they contain 5' phosphates. At least 60%
      of the genome must encode proteins. In the sequenced portion, many open reading
      frames exist and these are tightly packed together. These have been examined for
      homology to published proteins but only 1 to 17 shows similarity to known
      proteins. F01 is therefore the prototype of a new phage family. On the basis of
      restriction sites, codon usage and the distribution of nonsense codons in the
      unused reading frames, a strong case can be made for natural selection that
      reacts to mRNA structure and function.

PMID- 11981973
TI  - Detection of bacteria using foreign DNA: the development of a bacteriophage
      reagent for Salmonella.
AB  - A phage-based reagent was developed for the detection of Salmonella in food
      samples. The parental phage was Felix 01, which lyses practically all Salmonella.
      Using data obtained about the molecular biology of the phage, a recombinant phage
      that carried the bacterial genes specifying luciferase was produced. The method
      involved the isolation of amber nonsense mutations and subsequent crosses to
      render doubly mutant phage with a very low reversion rate on strains lacking an
      amber suppressor. A plasmid was constructed that contained a segment of Felix 01
      DNA with two adjacent genes, one dispensable and the other essential, and their
      flanking sequences. Recombinant DNA technology was used to remove the two genes
      and the luxA and luxB genes for luciferase, and a gene specifying a tRNA that
      recognizes amber codons (supF=tyrT) was put in their stead. This region could be
      transferred into the genome of the phage by homologous recombination. The
      recombinant phage cannot grow because it lacks an essential gene. However, it can
      grow in a host that synthesizes the missing protein. This technique allows the
      construction of "locked" recombinant phages that carry foreign DNA but which
      cannot propagate themselves in nature.

PMID- 11981974
TI  - Abstracts of the 12th Annual Meeting of the European Society of Human
      Reproduction and Embryology. Maastricht, The Netherlands, June 30-July 3, 1996.

PMID- 11981975
TI  - Abstracts of the 14th annual meeting of the Netherlands Association of Internal
      Medicine. Veldhoven, The Netherlands, 24-26 April 2002.

PMID- 11981976
TI  - [Abstracts of the 75th Annual Meeting of the Japan Society for Occupational
      Health. April 2002, Kobe, Japan].

PMID- 11981977
TI  - Understanding ship-grounding impacts on a coral reef: potential effects of anti
      foulant paint contamination on coral recruitment.
AB  - The 184 m cargo ship Bunga Teratai Satu collided with Sudbury Reef, part of the
      Great Barrier Reef and remained grounded for 12 days. The ship was re-floated
      only 3 days prior to the November 2000 mass coral spawning. No cargo or fuel was
      lost but the impact resulted in significant contamination of the reef with anti
      foulant paint containing tributyltin (TBT), copper (Cu) and zinc (Zn). Larvae of
      the reef-building scleractinian coral Acropora microphthalma were exposed to
      various concentrations of sediment collected from the grounding site in
      replicated laboratory experiments. Two experiments were performed, both of which
      used varying ratios of contaminated and control site sediment in seawater as
      treatments. In the first experiment, the influence of contaminated sediment on
      larval competency was examined using metamorphosis bioassays. In the second, the
      effect of contaminated sediment upon larval recruitment on pre-conditioned
      terracotta tiles was assessed. In both experiments, sediment containing 8.0 mg
      kg(-1) TBT, 72 mg kg(-1) Cu and 92 mg kg(-1) Zn significantly inhibited larval
      settlement and metamorphosis. At this level of contamination larvae survived but
      contracted to a spherical shape and swimming and searching behaviour ceased. At
      higher contamination levels, 100% mortality was recorded. These results indicate
      that the contamination of sediment by anti-fouling paint at Sudbury Reef has the
      potential to significantly reduce coral recruitment in the immediate vicinity of
      the site and that this contamination may threaten the recovery of the resident
      coral community unless the paint is removed.

PMID- 11981978
TI  - The inhibition of marine nitrification by ocean disposal of carbon dioxide.
AB  - In an attempt to reduce the threat of global warming, it has been proposed that
      the rise of atmospheric carbon dioxide concentrations be reduced by the ocean
      disposal of CO2 from the flue gases of fossil fuel-fired power plants. The
      release of large amounts of CO2 into mid or deep ocean waters will result in
      large plumes of acidified seawater with pH values ranging from 6 to 8. In an
      effort to determine whether these CO2-induced pH changes have any effect on
      marine nitrification processes, surficial (euphotic zone) and deep (aphotic zone)
      seawater samples were sparged with CO2 for varying time durations to achieve a
      specified pH reduction, and the rate of microbial ammonia oxidation was measured
      spectrophotometrically as a function of pH using an inhibitor technique. For both
      seawater samples taken from either the euphotic or aphotic zone, the
      nitrification rates dropped drastically with decreasing pH. Relative to
      nitrification rates in the original seawater at pH 8, nitrification rates were
      reduced by ca. 50% at pH 7 and more than 90% at pH 6.5. Nitrification was
      essentially completely inhibited at pH 6. These findings suggest that the
      disposal of CO2 into mid or deep oceans will most likely result in a drastic
      reduction of ammonia oxidation rates within the pH plume and the concomitant
      accumulation of ammonia instead of nitrate. It is unlikely that ammonia will
      reach the high concentration levels at which marine aquatic organisms are known
      to be negatively affected. However, if the ammonia-rich seawater from inside the
      pH plume is upwelled into the euphotic zone, it is likely that changes in
      phytoplankton abundance and community structure will occur. Finally, the large
      scale inhibition of nitrification and the subsequent reduction of nitrite and
      nitrate concentrations could also result in a decrease of denitrification rates
      which, in turn, could lead to the buildup of nitrogen and unpredictable
      eutrophication phenomena. Clearly, more research on the environmental effects of
      ocean disposal of CO2 is needed to determine whether the potential costs related
      to marine ecosystem disturbance and disruption can be justified in terms of the
      perceived benefits that may be achieved by temporarily delaying global warming.

PMID- 11981979
TI  - Transport and sedimentation of Cu in a microtidal estuary, SE Norway.
AB  - The transport and sedimentation of copper in the Glomma estuary, SE Norway during
      a period of 90% reduction in the industrial input of Cu, was studied from
      sediment trap material and compared to samples of the bottom sediments. Traps
      were deployed at four stations for several monthly periods during 1990, 1994 and
      1995. Trapped material was analysed for suspended particulate matter (SPM), total
      organic carbon (TOC) and nitrogen (TN), Cu, and Al. Only about 10% of the Cu from
      the river is trapped in the estuary. Still there was a moderate but significant
      reduction in Cu concentration in the trap SPM from 1990 to 1994, reflecting the
      industrial reductions, but only if excluding summer samples apparently influenced
      by antifouling Cu from boat paint. Settling matter therefore seems appropriate
      and sensitive for monitoring changes in the Cu load. The results supported the
      view that TOC is the main carrier of Cu to the sediments.

PMID- 11981980
TI  - Seasonal variation of polychlorinated biphenyl concentrations in the southern
      part of the Baltic Sea.
AB  - The impact of seasonal fluctuations in forcing factors such as atmospheric
      concentration, temperature, and biological productivity on the concentration of
      polychlorinated biphenyls (PCBs) in the surface water of the southern part of the
      Baltic Sea was investigated. Water samples were collected on eight cruises over 2
      years. A clear seasonal variability in dissolved PCB concentrations was observed
      with higher levels in summer than in winter and spring. This was attributed to
      changes in atmospheric concentrations and water temperature, based on
      measurements showing the PCB levels in the atmosphere and surface water to be
      close to a partitioning equilibrium. Concentrations in the suspended particulate
      material (SPM) fraction were also variable, and when the quotient of the organic
      carbon normalised concentration in SPM and the dissolved concentration was
      calculated (i.e., the bioaccumulation factor (BAF)), a seasonal pattern was
      observed which was consistent with kinetic limitations on partitioning into
      particles caused by plankton growth. However, seasonal variability in the
      partitioning properties of the SPM may also contribute to this variability.

PMID- 11981981
TI  - Contaminant levels in the muscle of four species of fish important to the
      recreational fishery of the New York Bight Apex.

PMID- 11981982
TI  - The future of fisheries--marine protected areas--a new way forward or another
      management glitch?

PMID- 11981983
TI  - Natural resource damage assessments in the United States: rules and procedures
      for compensation from spills of hazardous substances and oil in waterways under
      US jurisdiction.
AB  - Natural Resource Damage Assessment (NRDA) procedures in the US involve the use of
      uniform federally approved rules and procedures to assess economic losses and/or
      address restoration of injured resources that result from spills of hazardous
      substances and/or oil and petroleum substances in waterways under US
      jurisdiction. This effort started in the 1980s and involves two federal agencies
      that have developed separate federally approved procedures and rules, the US
      Department of Interior (US DOI) and the US Department of Commerce, National
      Oceanographic and Atmospheric Administration (US DOC, NOAA). This paper provides
      a brief overview of the federal laws applicable to resource damage assessments in
      the US, review of NRDA rules and procedures, and progress to date regarding US
      cases.

PMID- 11981984
TI  - [Abstracts from the satellite symposium of the Neurology Meeting of the French
      Speaking Community. Tours, France, 2-6 April 2002].

PMID- 11981985
TI  - [Abstracts of the Neurology Meeting of the French-Speaking Community. Tours,
      France, 2-6 April 2002].

PMID- 11981986
TI  - APICON 2002. Association of Physicians of India 57th Joint Annual Conference.
      January 13-17, 2002. Abstracts.

PMID- 11981987
TI  - Abstracts of the American Society of Hypertension 17th Annual Meeting. May 14-18,
      2002, New York, New York, USA.

PMID- 11981988
TI  - Understanding a practice venue: guidelines and suggestions regarding the non
      clinical aspects of neonatology.

PMID- 11981989
TI  - Abstracts of the American Geriatrics Society Annual Meeting. May 8-12, 2002,
      Washington, DC, USA.

PMID- 11981990
TI  - Parents' consent to the post-mortem removal and retention of organs.
AB  - Parents of children who died following complex heart surgery have recently
      discovered that organs were removed and retained in post-mortem investigations to
      which they consented. It has been established that many of these parents did not
      give informed consent to the retention of organs. The Bristol Royal Infirmary
      Inquiry which examined these practices drafted codes of practice to govern future
      post-mortem activities. It is argued that these codes of practice may be onerous
      to some parents, yet effectively disbar them from dissenting to their application
      whilst they might otherwise agree to the post-mortem removal and retention of
      organs for purposes of medical audit, research or training. This consequence
      arises from employing an over-rigorous concept of informed consent in the
      immediate circumstances of bereavement. That concept is discussed in detail. An
      alternative proposal is canvassed which improves on the status quo but does not
      impose a practice of consent which may be burdensome and distressing to many.

PMID- 11981991
TI  - Ethics, deception, and 'Those Milgram experiments'.
AB  - Critics who allege that deception in psychology experiments is unjustified
      frequently cite Stanley Milgram's 'obedience experiments' as evidence. These
      critics say that arguments for justification tend to downplay the risks involved
      and overstate the benefits from such research. Milgram, they add, committed both
      sins. Critics are right to point out that research oversight is often susceptible
      to self-serving abuse. But stating a priori how beneficial a given experiment
      will be is a tall order for psychologists, or anyone else. At the same time,
      critics themselves have difficulty in showing what is wrong with deception, and
      how subjects in these experiments suffer. Hence, it becomes unclear what the
      psychologists, including Milgram, are prone to downplay. There is also room to
      wonder how the Milgram studies can illuminate the debate over deception. Although
      Milgram probably exaggerated the scientific significance of his own work, critics
      who exaggerate its moral and historical significance do little to clarify the
      status of deception.

PMID- 11981992
TI  - "Are you my mommy?" On the genetic basis of parenthood.
AB  - What exactly is it that makes someone a parent? Many people hold that parenthood
      is grounded, in the first instance, in the natural derivation of one person's
      genetic constitution from the genetic constitution of others. We refer to this
      view as "Geneticism". In Part I we distinguish three forms of geneticism on the
      basis of whether they hold that direct genetic derivation is sufficient,
      necessary, or both sufficient and necessary, for parenthood. (Call these
      'Sufficiency', 'Necessity', and 'Strong' Geneticism, respectively.) Part I also
      explores the relationship between geneticism and the debate over surrogacy. Parts
      two through four examine three arguments for geneticism: the Property argument,
      the Causal argument, and the Parity argument. We conclude that none of these
      arguments succeeds. The failure of positive arguments for a view cannot
      demonstrate that the view is false; however, in light of our arguments we
      provisionally conclude that 'Strong' and 'Necessity' Geneticism are unacceptable.
      Our arguments do not undermine 'Sufficiency' Geneticism, so this thesis is
      considerably more promising than the others. But sufficiency geneticism is also
      compatible with a much more pluralistic account of the nature of parenthood.

PMID- 11981993
TI  - Markets and the needy: organ sales or aid?
AB  - As organ shortages have become more accute, support for a market in organs has
      steadily increased. Whilst many have argued for such a market, it is Gerald
      Dworkin who most persuasively defends its ethics. As Dworkin points out, there
      are two possibilities here--a futures market and a current market. I follow
      Dworkin in focusing on a current market in the sale of organs from living donors,
      as this is generally considered to be the most difficult to justify. One of the
      most pressing concerns here is that such a market will exploit the poor. I
      outline this concern and scrutinize Dworkin's and others' rejection of it.
      Briefly, I argue that the arguments Dworkin employs for allowing the poor to sell
      their organs fail, and in fact better support an argument for increasing aid to
      the needy.

PMID- 11981994
TI  - Two cheers for human cloning.

PMID- 11981995
TI  - German panel recommends imports of stem cells.

PMID- 11981996
TI  - Australian doctors admit helping patient die.

PMID- 11981997
TI  - China resists efforts to make donation of organs feasible.

PMID- 11981998
TI  - Baby spared mother's fate by genetic tests as embryo.

PMID- 11981999
TI  - Genes, embryos and ethics.

PMID- 11982000
TI  - Questions raised of conflicts at 2 hospital buying groups.

PMID- 11982001
TI  - Medical first: a transplant of a uterus.

PMID- 11982002
TI  - Irish voters reject broader ban on abortions.

PMID- 11982003
TI  - Hospital is fined for "woeful care": Mt. Sinai cited for deficiencies after liver
      donor's death.

PMID- 11982004
TI  - House votes to protect aborted fetus "born alive".

PMID- 11982005
TI  - Scientist at work: Leon Kass: moralist of science ponders its power.

PMID- 11982006
TI  - Liver donors face perils known and unknown.

PMID- 11982007
TI  - Race gap seen in health care of equally insured patients.

PMID- 11982008
TI  - Paralyzed woman has right to die, a British judge rules.

PMID- 11982009
TI  - Extending life, defibrillators can prolong misery.

PMID- 11982010
TI  - Dutch legalize euthanasia, the first such national law.

PMID- 11982011
TI  - Guantanamo. Navy doctors force-feeding 2 prisoners.

PMID- 11982012
TI  - Bush unveils bioethics council: human cloning, test on cloned embryos will top
      agenda of panel's 1st meeting.

PMID- 11982013
TI  - Questioning the biotech new world: leader of Council on Bioethics looks to the
      classics to help protect cultural values.

PMID- 11982014
TI  - Furor over cross-species cloning: fusing human DNA and egg of cow creates embryo-
      and world-wide debate.

PMID- 11982015
TI  - Community-based public health: a model for local success.

PMID- 11982016
TI  - Community-based public health: lessons on power, policy and grassroots
      leadership.

PMID- 11982017
TI  - The power of ordinary people.

PMID- 11982018
TI  - Cities as partners in community-based public health.

PMID- 11982019
TI  - Building powerful partnerships: the role of hospitals in community-based public
      health.

PMID- 11982020
TI  - What do schools have to do with community health?

PMID- 11982021
TI  - Participatory evaluation. What is it? Why do it? What are the challenges?

PMID- 11982022
TI  - The medical legacy of Gemini.
AB  - The Mercury and Gemini space flights have provided approximately 2,000 manhours
      of weightless exposure which can be used in comparing flight results with the
      predicted effects of manned space flight. In general the environmental hazards
      and the effects upon man appear to be of less magnitude than originally
      anticipated. The effects noted on the various body systems are summarized. The
      principal physiologic changes noted were orthostatism for some 50 hours post
      flight, reduced red cell mass, and reduced X-ray density in the os calcis and the
      small finger. Much was learned about man's ability to work in a pressurized suit
      in the extravehicular condition. Early biochemical findings have pointed the way
      to future investigations. All of these findings are of importance in relation to
      the planning for future long duration missions. Although much remains to be
      learned, it does appear from an overview of this medical legacy that if man is
      properly supported and evaluated his limitations will not be a barrier to the
      exploration of the universe.

PMID- 11982023
TI  - Life sciences and space research VI: proceedings of the Open Meeting of Working
      Group V of the Tenth Plenary Meeting of COSPAR, London, 27-28 July 1967.

PMID- 11982024
TI  - The biological effectiveness of solar electromagnetic radiation in space.
AB  - An attempt has been made to determine the solar ultraviolet action spectrum for
      dried coliphage T-1 exposed to space under various filters at sounding rocket
      altitudes between 80 to 150 km. The survival of these microorganisms was compared
      with the preliminary results of laboratory ultraviolet irradiation experiments
      using monochromatic light sources of wavelengths of 1633 angstroms, 2062
      angstroms, 2537 angstroms and of 3064 angstroms to 3200 angstroms. The results
      indicate that ultraviolet light of wave-lengths between 2000 angstroms to 3000
      angstroms was mainly responsible for the killing of the filter protected
      microorganisms. More studies of the biological action spectrum of the vacuum
      ultraviolet light including the Lyman alpha emission are needed to determine the
      cause of the more than 100 fold higher death rate of the microorganisms which
      were not protected during the space exposure by filters.

PMID- 11982025
TI  - The survival of terrestrial microorganisms in space at orbital altitudes during
      Gemini satellite experiments.
AB  - In a previous series of rocket- and satellite-borne experiments, microorganisms
      were exposed to space between altitudes of 60 to 460 km for periods between 3
      minutes and 4 months. The results showed that some of the unprotected
      microorganisms survived the direct exposure for up to 17 hours. Complete survival
      was found when the microorganisms were shielded from nonpenetrating radiation.
      These results made it desirable to systematically study the lethal influence of
      the space environment on a wider spectrum of unprotected microorganisms over
      various exposure periods. This communication presents the results of exposure
      experiments on board the Gemini XII satellite. The microorganisms were dried on
      plastic coated aluminum plates using techniques which will be described
      elsewhere. During the flight of the Gemini XII space capsule, the microorganisms
      were directly exposed to space for approximately 6 1/2 hours. After the
      successful completion of the Gemini XII mission the payload was returned to the
      laboratory for elution and titration of the microorganisms using techniques
      described elsewhere. The results showed that again survival of some
      microorganisms had occurred. An attempt is made to integrate these results with
      data obtained in previously published experiments.

PMID- 11982026
TI  - Microbiological studies on the radiation environment of the ionosphere and
      stratosphere.
AB  - Rocket, balloon and laboratory experiments have been performed in order to study
      the survival chances of microorganisms, which exist under the environmental
      conditions of ionosphere and stratosphere. The main results are: 1. Not only near
      the earth, but also in the stratosphere and even in the ionosphere,
      microorganisms are endangered primarily by UV- and EUV-light irradiation. 2. The
      observed effect of more penetrating kinds of radiation was relatively
      unimportant. High-vacuum and temperature effects have not been observed at all.
      Even membrane filters and thin protein layers protected the exposed spores of
      Bacillus subtilis var. niger (= Bac. globigii) in a clear-cut manner. 3. UV-light
      with a wavelength between 200 and 300 nm reduces the number of cells able to
      divide much quicker, than EUV-light of the same energy level does, but damages
      caused by EUV-light can not be reversed by photoreactivation. 4. Microbes which
      have been damaged by solar radiation, can be photoreactivated to a degree.
      Photoreactivation is high after exposure near the Earth and significant after
      exposure within the stratosphere. 5. After exposure to ionospheric irradiations
      no changes in the antigenic behavior of E. coli cells could be detected.

PMID- 11982027
TI  - Experimental biological life support system. II. Gas exchange between man and
      microalgae culture in a 30-day experiment.
AB  - The experiments of a prolonged stay by man in a closed atmosphere regenerated by
      a biological method have been examined. In the course of the experiment, a study
      of isolated and compatible links of a gas-closed system of "man-microalga" was
      carried out. The main emphasis was placed on the study of the biological
      compatibility of the links of the system and primarily of the effect of gaseous
      metabolites built up in the system of man. The dynamics of a number of
      physiological parameters of the man under experiment were studied. The regular
      functional tests of the respiratory and cardiovascular system were carried out.
      An electrocardiogram was made and respiratory rate and pulse were registered.
      Oxyhemogram investigations and laboratory clinical examinations were also
      performed, as well as some psychological tests. It was possible to equalize the
      respiratory gas ratio by the composition of the cultural environment for algae
      and by the nutrition ration of man. This eliminates time limit for the life
      maintenance system, especially on microalga photosynthesis. The results of the
      experiments permit drawing a conclusion on the biological compatibility of man
      and microalgae in their prolonged direct gas contact. Thus the possibility of
      obtaining a balanced atmosphere regeneration system on the basis of
      counterbalanced gas exchange between man and controlled photosynthesis of algae
      has been proven experimentally.

PMID- 11982028
TI  - [Psychomotor reaction in primates placed in ballistic flight in rockets].
AB  - Psychomotor reactions have been studied in Nemestrina Macaques during flights in
      rockets in which there were periods of weightlessness lasting about 10 minutes.
      The animals had undergone motor conditioning and responded to a light signal by
      pressing on a button placed on a panel where there were four other
      undifferentiated buttons. The lighting of the panel and pressing on the different
      buttons in reply was recorded with respect to time. Movement was observed by film
      recording, and electrical activity of the brain was kept under observation by six
      different recordings of the cortex. Activity of stretching and bending muscles of
      the legs was recorded, as well as breathing, and heart activity was recorded on
      an electrocardiogram. These psychological parameters were transmitted to the
      earth by long-distance measurement during the entire flight. The recordings made
      it possible to confirm that the absence of the sensation of weight seems to
      reduce the alertness of the animals. This fact had already been observed in
      Wistar's rat and cat. The sensor-psychomotor responses undergo important
      individual variations and depend on the motivation of the subjects. A very well
      motivated one reacted after a short period of adaption, as it did in the
      laboratory: one that was much less motivated would not work until after
      weightlessness has ended, and showed signs of drowsiness. These observations made
      during the flights in rockets confirm those of Chambers et al., Harris et al.,
      Lilly et al. made in immersion studies; they show the important role of weight in
      maintaining alertness, but that changes of psychomotor activity are particularly
      related to motivation.

PMID- 11982029
TI  - Resistance of organisms to extreme influences in relation to some exobiological
      problems.
AB  - The conditions to which organisms have not been able to adapt in the process of
      evolution are called extreme influences or extreme conditions. The experiments
      show that organisms and cells have a potential for resistance; among animals,
      there are forms that are able to stand extremely low temperatures (from -80 to 
      269 degrees) when the water content of their tissues is large enough. Some
      species of protozoa can tolerate ionizing radiation in doses (500-1800 kr) of
      many orders exceeding those existing on the Earth and out in space. There are
      different ways of obtaining "protection" against ultraviolet (UV) shortwave sun
      radiation detained by the ozone layers of the Earth's atmosphere
      (photoreactivation, biological screens non-permeable for UV light, etc.). Many
      insects, especially alpine species, do not require as much oxygen as is contained
      in lower layers of the Earth's atmosphere. Hence, earth organisms possess some
      "margins of safety", enabling us to suggest the existence of similar biological
      systems in conditions different from the Earth's. The resistance to the action of
      extreme factors is probably connected with the resistance of biopolymers, protein
      complexes of cells and also with the capability of the organism to recover from
      damage.

PMID- 11982030
TI  - Weightlessness and the developing frog egg.
AB  - This paper describes the results of the flight of fertilized frog eggs in the
      manned orbital flights Gemini 8 and Gemini 12. The experiment was designed to
      determine the effect of weightlessness or near weightlessness on the ability of
      the cell to divide normally and on subsequent differentiation and embryogenesis.
      Eggs were fixed periodically in flight so that recovered material could be
      carefully compared to simultaneous ground controls with respect to gross
      morphology and histology. Some embryos were recovered alive after 4 days in
      orbit. In general, no abnormalities were detected which were inconsistent with
      the controls. Death, shortly after recovery, of the embryos recovered alive in
      Gemini 12, remains unexplained. The protocol of the experiment and the
      experimental hardware is described. Rationale for future experiments is
      discussed.

PMID- 11982032
TI  - The time has come for interventional studies in transcultural nursing and health
      care.

PMID- 11982031
TI  - Orthopedic devices: reclassification of the hip joint metal/polymer constrained
      cemented or uncemented prosthesis. Final Rule.
AB  - The Food and Drug Administration (FDA) is reclassifying the hip joint
      metal/polymer constrained cemented or uncemented prosthesis intended to replace a
      hip joint from class III (premarket approval) to class II (special controls). FDA
      is also [[Page 21172]] identifying the guidance document entitled "Class II
      Special Controls Guidance Document: Hip Joint Metal/Polymer Constrained Cemented
      or Uncemented Prosthesis" as the special control that the agency believes will
      reasonably ensure the safety and effectiveness of the device. This
      reclassification is being undertaken based on new information regarding the
      device contained in a reclassification petition submitted by the Orthopedic
      Surgical Manufacturers Association (OSMA), under the Federal Food, Drug, and
      Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the
      1976 Amendments), the Safe Medical Devices Act of 1990 (SMDA), and the Food and
      Drug Administration Moderization Act of 1997 (FDAMA). FDA is also revising the
      device identification to accurately describe the device.

PMID- 11982033
TI  - Take-a-village (TAV): a metaphorical model for health promotion.
AB  - Because of the emerging minority concept in American society, nursing in the new
      millennium is committed to designing culturally appropriate community health
      nursing models. The purpose of this article is to build one metaphorical model
      for health promotion inductively from substantive data obtained in a qualitative
      research. In one study, the take-a-village (TAV) construct was conceptualized as
      a kin and a social network system. TAV was born out of a popular African adage
      that "it takes a village to raise one single child." The TAV model emerged during
      the analysis phase of the study. This model-building exercise explored the tenets
      of the TAV construct for use in building a community health practice model for
      health promotion.

PMID- 11982034
TI  - An explanatory model of preterm labor.
AB  - The purpose of this article is to describe women's explanatory model of their
      preterm labor (PTL) experiences. Fourteen young adult (20 to 23 years of age)
      women living in the southeast, who were hospitalized for the treatment of PTL,
      participated in this naturalistic study. Stress was the dominant theme that all
      participants used to explain what had precipitated PTL. All women described
      multiple stressors and chaos in their lives, which preceded their admission to
      the hospital for PTL. Meanings of PTL were intertwined with dysfunctional
      families and problematic relationships. All 9 women who delivered at term were
      able to find a friend or family member to provide support that allowed the women
      to relax and reduce the stress in their lives. In contrast, women who delivered
      preterm had no one in their lives that could provide help and support. Women's
      conceptualizations of PTL suggest that culturally appropriate interventions to
      reduce stress and mobilize support may help improve birth outcomes after an
      episode of PTL.

PMID- 11982035
TI  - Korean American caregivers: who are they?
AB  - PURPOSE: To describe the caregiving role in the Korean American family. DESIGN:
      Descriptive study. METHOD: Thirty Korean American female caregivers were
      interviewed using a semistructured questionnaire related to sociodemographic
      background, caregiving history, filial responsibility, family network, cognitive
      status, dependency level, job-caregiving conflict, family conflict, economic
      strain, and negative life-style changes. FINDINGS: The Korean American caregivers
      were elderly wives who were sharing households only with their elderly husbands,
      and these women were low-income, unemployed, less educated, and regarded their
      caregiving activity as a final assignment of obligation and duty given to them as
      spouse. DISCUSSION: The Korean traditional cultural norm of filial piety plays a
      significant role for caregiving activities among Korean American caregivers.
      IMPLICATION: Understanding cultural norms may enable health care providers to
      look below the surface even though caregivers may not express problems.

PMID- 11982036
TI  - Cultural care of Thai immigrants in Uppsala: a study of transcultural nursing in
      Sweden.
AB  - The purpose of this study was to discover and describe the meanings and
      expressions of cultural care of a group of Thai immigrants in Sweden.
      Participants included 15 key informants and 24 general informants living in and
      around the town of Uppsala. The conceptual framework was provided by Leininger's
      theory of cultural care diversity and universality. Use was made of the
      ethnonursing method and the Sunrise Model in the search for multiple and related
      dimensions that influenced the generic and professional care practices of the
      Thai immigrants. Four major themes were formulated. Thus, care (a) means family
      and kinship relationships as expressed in daily life, (b) is expressed in
      traditional gender roles, (c) means religious beliefs as expressed in the
      Buddhist worship, and (d) means support of traditional health care practices.
      These themes support the cultural care theory and also confirm the Sunrise Model.

PMID- 11982037
TI  - Health care experiences and beliefs of elderly Finnish immigrants in Sweden.
AB  - PURPOSE: To elucidate the experiences and beliefs of care of elderly Finnish
      immigrants living in Sweden (Sweden-Finns) in order to gain an understanding of
      the role ethnic background plays in these experiences and beliefs. DESIGN: 39
      elderly Sweden-Finns living in Stockholm were interviewed. The data were analysed
      hermeneutically. RESULTS: On a surface level, the care in Sweden was culturally
      congruent to elderly Sweden-Finns' experiences and beliefs of care. However, care
      in Finland and the care providers with Finnish background were regarded as
      superior to Swedish caregivers, giving a deeper sense of familiarity and trust in
      anticipation of good care. IMPLICATIONS FOR PRACTICE: Culturally appropriate care
      with care providers sharing the same ethnic background is important for ethnic
      elderly persons in enabling familiarity and trust between staff and patients.

PMID- 11982038
TI  - Exploring parish nursing from an ethnographic perspective.
AB  - PURPOSE: This study examined a parish program as an evolving nursing specialty.
      DESIGN: This is an ethnographic study of a parish nursing program in a
      southeastern U.S. city that included interviews with key informants, participant
      observations, and document analysis. Data were content analyzed. FINDINGS AND
      RESULTS: Findings indicate positive perceptions of the parish nursing program.
      Cultural themes include the process of discovery, commitment to the parish nurse
      and program, and fit with values and missions. Taxonomies of parish nurse
      attributes, actions, offerings, roles, and entrance requirements were derived.
      DISCUSSION AND CONCLUSION: Parish nursing offers nurses the opportunity to bridge
      physical, social, emotional, and spiritual lives into one caregiving experience.
      IMPLICATIONS FOR PRACTICE: Findings provide clinical guidance for parish nurses.

PMID- 11982040
TI  - Founder's focus: transcultural nursing is discovery of self and the world of
      others.

PMID- 11982039
TI  - Transcultural nursing concepts and experiences in nursing curricula.
AB  - Future trends in the convergence of a multicultural world continue to intensify
      the need to educate nurses to deliver culturally focused care. A descriptive
      survey was conducted to examine curricular trends related to the teaching of
      transcultural nursing (TCN) in nursing curricula of baccalaureate and higher
      degree schools of nursing in the United States. Faculty development and
      qualifications to teach transcultural nursing were identified as well as methods
      for collaboration between schools of nursing. Although TCN concepts are
      incorporated into most curricula, wide variation exists as to content, depth, and
      level of integration. Implications call for collaboration with accrediting
      agencies, including state boards of nursing, to strengthen expected outcomes
      related to culture, curricular reviews of nursing courses regarding the
      incorporation of TCN concepts and experiences, collaboration on culturally
      focused field experiences, faculty development, and networking across schools to
      expand available resources.

PMID- 11982041
TI  - Updated HIV treatment guidelines available on-line.

PMID- 11982042
TI  - Defining care in the culture of the chronically mentally ill living in the
      community.
AB  - The ethnonursing method was used to discover care meanings, expressions, and
      experiences of the chronically mentally ill to guide nurses in promoting the
      health and well-being of these people. Fifteen key and 24 general informants were
      interviewed. Six major themes were abstracted: (a) care as listening and giving
      presence is meaningful to the chronically mentally ill; (b) they desire to give
      care to others; (c) they are a subculture; (d) mental illness carries a public
      stigma in the dominant culture; (e) flexible and growth-promoting care practices
      are desired; and (f) the chronically mentally ill desire normalcy but fear
      rejection by the dominant culture.

PMID- 11982043
TI  - Perceptions and experiences with nursing care: a study of Pakistani (Urdu)
      communities in the United Kingdom.
AB  - The population of the United Kingdom reflects rich cultural diversity. Hence,
      nursing must respond to the challenges of meeting the needs of different ethnic
      groups and fulfilL the requirements of the Code of Professional Conduct. This
      article presents the findings of a study using grounded theory to explore the
      lived experience of Pakistani (Urdu-speaking) communities that received nursing
      care in a hospital setting in the United Kingdom. The study reflects national
      initiatives toward "consumer led" health care delivery. The findings illustrate a
      lack of congruence between the group's expectations and their experiences. Nurses
      were perceived to have a poor understanding of ethnic needs, portraying
      ethnocentric attitudes and behaviour. The participants attributed the lack of
      congruence mainly to the presence of racism in British health care systems. The
      author suggests possible changes at the strategic, managerial, and educational
      levels of health care delivery.

PMID- 11982044
TI  - Ethics and cross-cultural nursing.
AB  - This article examines how cultural misunderstandings and language differences
      generate ethical dilemmas in cross-cultural nursing. It explores the consequences
      of actions that result when health care providers lack an awareness of the value
      systems of patients that differ from their own. Described are the principles
      arising from ethical theory, their application to nursing, and incorporation into
      professional codes of ethics. Two case studies illustrate the close relationship
      between culture, health, and communication, with language barriers a significant
      factor in predicting the outcomes of care. Recommendations are offered for
      cultural competency training for health care institutions, nursing
      administrators, and nursing educators.

PMID- 11982045
TI  - Development and psychometric evaluation of the transcultural self-efficacy tool:
      a synthesis of findings.
AB  - The initial and ongoing assessment of students' self-efficacy perceptions
      (confidence) concerning culture care of diverse individuals is a valuable
      component in transcultural nursing education. The Transcultural Self-Efficacy
      Tool (TSET) was designed as a diagnostic tool to measure and evaluate students'
      transcultural self-efficacy perceptions for performing general transcultural
      nursing skills among diverse client populations. This article summarizes the
      steps in the TSET's development and evaluation, synthesizes reliability and
      validity findings from a series of psychometric investigations, and discusses
      future research and educational applications in transcultural nursing using the
      TSET.

PMID- 11982046
TI  - Providing health care for lesbian clients.
AB  - Health and nursing care for lesbian clients should be culturally congruent with
      their values and lifestyle. Barriers that lesbian clients encounter in the health
      care system are discussed, along with strategies that health care providers can
      use to overcome these barriers. Professional literature is reviewed that
      incorporates health promotion and maintenance issues influencing lesbian health
      care. Culturally appropriate services that are available in one women's health
      center are described, and resources for interested health care providers are
      provided.

PMID- 11982047
TI  - Founder's focus--multidiscipline transculturalism and transcultural nursing.

PMID- 11982048
TI  - The effect of globalization on health care: a double-edged sword.

PMID- 11982049
TI  - The culture of war: a study of women military nurses in Vietnam.
AB  - Many books and studies have described the male Vietnam War culture, whereas
      similar literature about women is almost nonexistent. This study describes the
      culture of war nursing as experienced by 24 U.S. women military nurses. Data were
      generated using a core question and in-depth interviews. Phenomenology served as
      the research method, incorporating data analysis procedures of Colaizzi and
      Lincoln and Guba. Nine theme categories were identified to describe the culture
      of war nursing. Core values of the military culture were threaded throughout
      descriptions, and activities to make their environment more homelike embodied the
      positive values of their culture.

PMID- 11982050
TI  - The beliefs and practices of traditional birth attendants in the Manxili area of
      KwaZulu, South Africa: a qualitative study.
AB  - The World Health Organization recommends that people be within an hour of the
      nearest health care facility. In the Manxili region of KwaZulu, South Africa,
      difficult terrain and tribal fighting make this nearly impossible for pregnant
      women. Therefore, traditional birth attendants provide much of the midwifery
      services in this area. They have no medical training, and their beliefs and
      practices are not well understood. This study, therefore, gathered data on the
      beliefs and practices of seven attendants, using a case study analysis.
      Beneficial as well as harmful customs were identified and suggestions made for
      education of the attendants.

PMID- 11982051
TI  - Heart health and gender.
AB  - BACKGROUND: Although mortality from cardiovascular diseases is at least as high
      among women as among men, the notion that such illnesses are gender-specific,
      afflicting mainly males, continues to influence our present day understanding of
      heart disease. OBJECTIVE: To compare the average length of stay for men and women
      admitted to the CCU over a 14-month period. METHOD: All patients admitted to the
      CCU of a university-affiliated hospital over a 14-month period were included in
      the study (n = 167). T-test and chi-square were used to analyze means and
      percentages, respectively. RESULTS: Significantly more men than women gained
      admittance to the CCU during the time of this study (p < .001). Differences in
      average length of stay were not statistically significant, however. Similar
      numbers of men and women underwent cardiac catheterization. CONCLUSIONS: Gender
      considerations have emerged as a major issue in the diagnosis and treatment of
      heart disease in women. Although fewer women than men were admitted to the CCU
      during the study period, similar percentages had invasive interventions
      performed.

PMID- 11982052
TI  - Critical thinking: an epidemic of body and soul.

PMID- 11982053
TI  - Filter anticoagulation is accomplished through the administration of dilute
      heparin.

PMID- 11982054
TI  - Implementation of an RN/RT-initiated extubation protocol.
AB  - Widespread acceptance of the importance of discontinuing ventilator support at
      the earliest possible opportunity has resulted in a number of efforts to develop
      a standardized approach to extubation. The implementation of an extubation
      protocol designed for the medical/surgical intensive care unit of a university
      affiliated hospital followed a series of educational sessions that were open to
      all members of the multidisciplinary team. As part of quality assurance
      monitoring, data were collected on the first 47 patients who were extubated using
      these criteria. A clinical outcome was defined as the percentage of patients who
      required reintubation within 48 hours. The protocol has been well-received by the
      ICU team and has become an established component of ventilator management.

PMID- 11982055
TI  - Personality hardiness: an essential attribute for the ICU nurse?
AB  - Staff turnover has been a persistent problem in critical care units, magnified by
      stress and burn-out in nurses. Researchers studying the concept of personality
      hardiness over the past 20 years have suggested that it may play a protective
      role against stress and burn-out. Those who are able to effectively cope with
      stress and adapt to the uncertain environment of the ICU are less likely to leave
      it prematurely. The concept of personality hardiness is explored as it relates to
      adaptation of nurses to the ICU. Suggestions for development of hardiness are
      based on a review of relevant literature.

PMID- 11982056
TI  - Continuous venous hemodiafiltration with trisodium citrate anticoagulation in
      cardiac surgery patients.
AB  - Despite advances in perioperative organ protection during cardiovascular surgery,
      acute renal failure remains a serious complication. The purpose of this clinical
      article is to describe the role of continuous renal replacement therapy (CRRT) in
      proactive maintenance of fluid and electrolyte balance and treatment of acute
      renal failure in patients following cardiovascular surgery. Implications for
      nursing practice, education, and future research will be delineated using a case
      study of a patient who required mechanical circulatory support and CRRT. The
      complexity of the patient's care was compounded by the need to alter conventional
      anticoagulation therapy to trisodium citrate.

PMID- 11982057
TI  - Critical thinking: nurses' voice absent ... again.

PMID- 11982058
TI  - Treatment approaches to some childhood skin conditions.

PMID- 11982059
TI  - The contraceptive needs of women with learning disabilities.

PMID- 11982060
TI  - Recognising the importance of spirometry in primary care.

PMID- 11982061
TI  - Using cadexomer iodine in delayed wound healing.

PMID- 11982062
TI  - Choosing the right stoma appliance for an ileostomy.

PMID- 11982063
TI  - Smoking cessation gets a kickstart.

PMID- 11982064
TI  - Better delivery ensures low asthma drug doses.

PMID- 11982065
TI  - Going over the edge.

PMID- 11982066
TI  - Identifying deficits in nurses' training in ear care.

PMID- 11982067
TI  - Medicare home health agencies: overpayments hard to identify and even harder to
      collect.

PMID- 11982068
TI  - Breaux-Frist "reform" bill would destroy Medicare, advocates warn.

PMID- 11982069
TI  - Transcultural nursing: where do we go from here?

PMID- 11982070
TI  - The attitudes of black Americans toward advance directives.
AB  - PURPOSE: To describe how some Black Americans view advance directives. Current
      literature revealed that most prior studies used quantitative methods with force
      choice questions and had few Black subjects. DESIGN: Interviews were conducted
      with 17 Black Americans. Transcripts of the interviews were subjected to content
      analysis. FINDINGS: Three major categories of themes were identified: Threats to
      dignity, family relationships, and spirituality. Black Americans in this study
      did not desire unconditional end-of-life treatment. CONCLUSIONS: This sample had
      a positive attitude toward the utility of advance directives. Legally generated
      directives were not seen as necessary. IMPLICATIONS FOR PRACTICE: The alternative
      ways that Black Americans may conduct advance directing should be recognized.

PMID- 11982071
TI  - Puerto Rican cultural beliefs: influence on infant feeding practices in western
      New York.
AB  - The purpose of this study was to examine the cultural beliefs and practices of
      Puerto Rican families that influence feeding practices and affect the nutritional
      status of infants and young children. The goal of the study was to outline
      strategies that would enable nurses to provide culturally congruent care for this
      population. Culture care theory guided the research, and an ethnonursing
      methodology was used. From interviews with 10 key and 5 general informants, 11
      universal and 2 diverse themes were abstracted. The dimensions of kinship,
      cultural values, lifeways, and philosophical beliefs were found to influence
      Puerto Rican infant feeding practices. The cultural belief that big is healthy
      was found to be integrally related to cultural feeding practices. Strategies are
      suggested to facilitate provision of culturally congruent care for Puerto Rican
      infants and children in an ambulatory setting.

PMID- 11982072
TI  - Collaborative partnership for culture care: enhancing health services for the
      Arab community.
AB  - The purpose of this study was to discover perceptions, experiences, and patterns
      of health care behavior among Arab Americans in an urban Midwestern area of the
      United States and then to discover perceptions and experiences of health care
      providers related to culturally competent care. The goal of the study was to
      generate findings that would provide the basis for implementing system-wide
      changes to include culturally competent care. A qualitative focus group
      methodology was used to discover the care patterns and perceptions of Arab
      Americans and the local health care providers. The nurse researchers conducted 10
      focus groups. Six themes were identified, including the unique caring behaviors
      of Arab families, the complexity of the health care system to Arab Americans,
      communication gaps, the diversity of perceptions of cultural competency,
      obstacles to accessibility of care, and workforce diversity issues.

PMID- 11982073
TI  - A description of the Purnell Model for Cultural Competence.
AB  - To meet the needs of a multicultural society, health care in the new millennium
      stresses teamwork in providing culturally sensitive and competent care to improve
      client outcomes. Publications addressing the future predict an increasingly
      diverse workforce. Accordingly, care providers can benefit from a conceptual
      model of cultural competence that can be used by all health disciplines in all
      practice settings. The Purnell Model for Cultural Competence, developed in 1995,
      is applicable to all health care providers. This article (a) describes the
      development of the model; (b) provides a description of the model; (c) lists the
      major assumptions on which the model is based; (d) describes the model's use in
      practice, education, administration, and research across disciplines; and (e)
      includes a brief evaluation of the model. Important cultural domains missing from
      other transcultural and cross-cultural models, which are found in the Purnell
      Model, are biocultural ecology and workforce issues.

PMID- 11982074
TI  - Perinatal care: cultural and technical differences between China and the United
      States.
AB  - A comparison of perinatal care in the U.S. and China is presented. Perinatal care
      has made tremendous achievements in both countries since mid-century. However,
      the outcomes in the two cultures are different due to the different focus on
      caring concepts, the strengths of a nursing philosophy, and the emphasis on the
      nursing role in maternal care. Perinatal family in the U.S. will have advantages
      in perinatal education physical facilities, and a philosophy of care. North
      American women have greater access to early prenatal and continuing care, and
      less infant mortality. Chinese women have less access to qualified nursing
      services, higher infant mortality rates, and limited perinatal education.
      Overall, Chinese perinatal care is far behind that which is found in the U.S.
      This comparison analyzes the strengths and weaknesses in both cultures with a
      focus on change that will produce healthier and more consistent optimal outcomes.

PMID- 11982075
TI  - Impression management: an alternative to assertiveness in intercultural
      communication.

PMID- 11982076
TI  - Breast-feeding experiences of women of African heritage in the United Kingdom.
AB  - This article explores the breast-feeding experiences of women of African descent
      in the United Kingdom. Although there is a limited evidence base that describes
      the breast-feeding experiences of these women, the small number of studies on
      this topic suggest that a tradition of breast-feeding exists within African
      communities in the United Kingdom. Cultural materialism is adopted as a
      theoretical framework to explore the sociocultural influences on breast-feeding
      in the United Kingdom for this group. The invisibility of this group is examined
      in relation to the health care research and policy agenda in the United Kingdom,
      and arguments are made for the urgent need to address this paucity of information
      to promote evidence-based nursing and midwifery practice.

PMID- 11982077
TI  - Building bridges to promote globalization in nursing: the development of a
      hermanamiento.
AB  - The establishment of a hermanamiento (sister school) partnership between Duquesne
      University School of Nursing in Pittsburgh, Pennsylvania, United States, and the
      School of Nursing at the Polytechnic University in Managua, Nicaragua, is
      described. Also discussed is the Regis Group Model, under which the hermanamiento
      was developed, and suggestions of how to develop a similar international nursing
      partnership. One component of a comprehensive model for international partnership
      and collaboration is presented in detail. The activities and goals that were
      established and implemented by both schools of nursing provide a philosophic and
      transcultural backdrop on which the program was based.

PMID- 11982078
TI  - Founder's focus--the third millennium and transcultural nursing.

PMID- 11982079
TI  - Dreams of the past--visions of the future: a participatory democracy.

PMID- 11982080
TI  - Co-ordinating care packages for people with multiple sclerosis.

PMID- 11982081
TI  - The effect of insulin resistance on diabetes management.

PMID- 11982082
TI  - Approaches to child safety and accident prevention.

PMID- 11982083
TI  - A person-centred holistic approach to dementia training.

PMID- 11982084
TI  - Providing appropriate nutrition in different disease states.

PMID- 11982085
TI  - Updated cleaning guidelines for the Propulse ear syringe.

PMID- 11982086
TI  - Meeting the needs of people with urinary incontinence.

PMID- 11982087
TI  - Measuring and assessing wounds effectively.

PMID- 11982088
TI  - Interpreting and analysing PACT data: Part II.

PMID- 11982089
TI  - Identifying and managing arterial ulceration.

PMID- 11982090
TI  - Malnutrition risk high in people with dementia.

PMID- 11982091
TI  - Fruit and veg for children.

PMID- 11982092
TI  - Osteoporosis seen too late.

PMID- 11982093
TI  - Becoming a nation of quitters.

PMID- 11982094
TI  - Assessment and screening for colorectal cancer.
AB  - Despite the reduction of and improvement in the survival rates for colon and
      rectum (colorectal) cancer, this form of cancer remains one of the most prevalent
      malignancies in the United States. More than 90% of colorectal cancer cases occur
      in people older than 50, the typical age group of home care provider clients.
      Educating these clients about the symptoms, screening methods, and treatments for
      colorectal cancer should be a routine part of the care provided by home health
      providers.

PMID- 11982095
TI  - Nutritional assessment in home care patients.
AB  - Nutrition, a critical requirement of all living organisms, involves several
      processes that must be maintained to sustain life. Nutrition consists of
      ingestion of food and fluid, digestion, absorption, distribution
      (transportation), utilization (metabolism), and excretion of the end products.
      Problems arise when the amount of various nutrients ingested is either deficient
      or excessive or when any of these processes are significantly altered.

PMID- 11982096
TI  - Providing nourishment at home.
AB  - In many aspects of patient care, technologic advances have changed the home care
      landscape. Treatment once believed available only to hospitalized patients has
      become, with the right multidisciplinary home care team, both feasible and
      equally effective. Nutrition delivery is among these advances in home care.

PMID- 11982097
TI  - Strategies to improve patient understanding.

PMID- 11982098
TI  - Gastroesophageal reflux disease.
AB  - In this age of fast food, overeating, and busy schedules, many people frequently
      complain of heartburn or indigestion. Meal times are rarely consistent, so meal
      planning appears out of the question. What are the consequences of this
      lifestyle? Gastroesophageal reflux disease (GERD) is a common disorder that
      affects every population. This article defines this condition and provides a
      history, literature review, and pathophysiology for the disorder. Recommendations
      for diagnosis and guidelines for treatment and nursing care interventions also
      are given.

PMID- 11982099
TI  - The implications of domestic violence for home care providers.

PMID- 11982100
TI  - Home care in Shanghai.

PMID- 11982101
TI  - Becoming accredited at the Joint Commission.

PMID- 11982102
TI  - Protection of confidential patient information under OASIS. Outcomes and
      Assessment Information Set.

PMID- 11982103
TI  - Ethical issues in management.
AB  - Home care takes place in a complex landscape in which multiple interests and
      responsibilities intersect in many ways and at many levels. These
      responsibilities include the agency to the public, management to care providers
      and vice versa, workers to each other, patients to workers, and workers to
      caregivers, to name but a few relationships. In such complicated situations, not
      surprisingly, some of these interests and responsibilities are at odds.

PMID- 11982104
TI  - Maintaining caregiving at home: a culturally sensitive grounded theory of
      providing care in Thailand.
AB  - Grounded theory methodology was used to generate a substantive theory that
      describes and explains the caregiving process of Thai caregivers for their
      elderly stroke relatives. Data were collected from a purposive sample of 20
      family caregivers living in Chachoengsao province, Thailand, by using interviews,
      observations, and the primary researcher's memos. The central idea emerging from
      the data was maintaining caregiving at home that encompassed these seven
      contextual situations: (a) caregiving as an integral part of life; (b) caregiving
      as an unavoidable task; (c) caregiving with love, sympathy, and attachment; (d)
      family and kinship support; (e) community support; (f) managing treatment; and
      (g) managing problems and difficulties. Culture, tradition, and religion
      dominated throughout these situations. Application of the theory is discussed
      relative to providing culturally sensitive nursing education, intervention, and
      research.

PMID- 11982105
TI  - Utilising the concept of protection in health maintenance among the Bena in
      Tanzania.
AB  - This article reports the findings of a study of the protective health care
      actions by the Bena. The article is based on an ethnographic research project
      that dealt with cultural care among the Bena tribe in the Ilembula villages in
      Tanzania. The data were collected with open-ended interviews and participatory
      observation. Forty-nine villagers were interviewed. The findings show that
      childhood and adulthood include some sensitive phases of the Bena life span that
      require protective actions to ensure reproductive, physical, and mental health.
      The following main protective actions were related to health protection in the
      sensitive phases: taking local herbs, avoiding sexual relations, hiding
      menstruation and early pregnancy from others, avoiding contacts with magic,
      avoiding kitchen work, using one's own utensils, and omitting greeting others.

PMID- 11982106
TI  - An exploration of health beliefs, lifestyle behaviours, and health needs of the
      London-based Greek Cypriot community.
AB  - This article reports selected results of the qualitative phase of a multimethod
      study into an investigation of the health beliefs, lifestyle behaviours, and
      health status of Greek Cypriots living in London. Data for this phase, which
      involved 79 informants, were collected through group and individual
      semistructured interviews. Six major themes were identified. These detail the
      informants' health and illness beliefs and use of folk remedies. The importance
      of the family as both a force for health and a cause for health problems is
      discussed. The informants' experiences as health users are also reported. The
      article concludes that culture is an important mediator for the health of this
      ethnic group. Culturally competent care depends on the nurses' understanding of
      the cultural background of their patients. The article recommends that nurses
      must be aware of the importance of societal and institutional structures that may
      discriminate against people from minority ethnic groups.

PMID- 11982107
TI  - Adapting a measure of acculturation for cross-cultural research.
AB  - Although Filipino Americans are projected to become the largest Asian American
      ethnic group in this millennium, no acculturation measure existed for this group.
      This article describes a systematic and replicable process used in adapting and
      modifying A Short Acculturation Scale for Hispanics (ASASH) for use with Filipino
      Americans. It depicts the multiple and iterative steps of translation and
      backtranslation to produce A Short Acculturation Scale for Filipino Americans
      (ASASFA) in English and in Tagalog--the Philippine national language. Also, it
      describes the methods undertaken for the measures to achieve linguistic and cross
      cultural validity through content, technical, experiential, semantic, and
      conceptual equivalence. With the dearth of linguistically and culturally valid
      measures for immigrant populations, the adaptation of valid measures developed
      for other cultures remains a viable option.

PMID- 11982108
TI  - A literary approach to teaching cultural competence.
AB  - Cultural competence is a necessity in today's diverse society and an essential
      component of clinical practice. As an adjunct to other sources, literature can
      enrich teaching and sensitize students to cultural issues in health care. The
      Spirit Catches You and You Fall Down is a beautifully written and compelling
      story well suited for instructional purposes. Although widely recommended, nurses
      are largely ignored in this story of a Hmong family seeking medical care. The
      book describes how the health care system failed to provide adequate care to
      patients from a different cultural background despite providers' good intentions.
      Nurse educators can use structured discussion guides to synthesize literary
      accounts such as The Spirit Catches You and You Fall Down with theory and
      research about cultural competence.

PMID- 11982109
TI  - Haitian ethnomedical systems and biomedical practitioners: directions for
      clinicians.
AB  - Since the 1980s, there has been a dramatic increase in immigration to the United
      States from Haiti. New and recent immigrants from Haiti are likely to have little
      prior experience with biomedical care and are also likely to have suffered from
      the physical and mental effects of poverty, malnutrition, and violence. Access to
      care for this vulnerable population may be hampered by a lack of available
      services as well as a general lack of understanding of Haitian spiritual and
      ethnophysiologic beliefs by biomedical practitioners. The purpose of this article
      is to present an overview of Haitian spiritual and ethnophysiologic beliefs
      within their historic context, provide an introduction to Haitian ethnomedicine,
      and offer suggestions for clinicians and researchers who work with this
      population.

PMID- 11982110
TI  - Cultural aspects of disability.
AB  - This article describes cultural and social issues related to disability based on
      the authors' experiences as researchers, clinicians, and activists and personal
      experience. They address the complexity of the topic of disability subculture by
      arguing that there is not one disability subculture and then describe common
      themes that characterize the social context of people with disabilities and one
      highly visible disability subculture. Clinical and research implications are
      mentioned. The definition of culturally competent care should be broadened to
      include disability.

PMID- 11982111
TI  - Critical thinking: significant changes for CACCN.

PMID- 11982112
TI  - Mental health: a report of the Surgeon General.

PMID- 11982113
TI  - Integration: the final frontier.

PMID- 11982114
TI  - Approaches to preventing an epidemic of obesity.

PMID- 11982115
TI  - Challenge of effective diabetes management in children.

PMID- 11982116
TI  - Nurses' attitudes to acting as patients' advocates.

PMID- 11982117
TI  - Know how. Penile sheaths.
AB  - Penile sheaths are used to manage some types of male urinary incontinence. This
      article examines the issues nurses need to address to make them effective, and
      outlines the choices of sheath available.

PMID- 11982118
TI  - Improving screening practices in the fight against chlamydia.

PMID- 11982119
TI  - The nurse's role in achieving optimal epilepsy management.

PMID- 11982120
TI  - Emergency contraception and its impact on teenage pregnancy.

PMID- 11982121
TI  - Choosing the right asthma inhaler device for children.

PMID- 11982122
TI  - Reforms set to open up new opportunities for nurses.

PMID- 11982123
TI  - Choosing the right dressings for managing arterial ulcers.

PMID- 11982124
TI  - The role of vaccination in travel health education.

PMID- 11982125
TI  - Asthma self-management plans need expansion.

PMID- 11982126
TI  - Assessing possible allergies to wound care products.

PMID- 11982127
TI  - Nutritional guidelines set out.

PMID- 11982128
TI  - Essential wound healing. Part. 7. Managing acute wounds.

PMID- 11982129
TI  - Cut turnover costs with five rights of hiring.
AB  - Effective nurse leaders recruit, place, and retain staff. Here's how to educate
      your managers to perform the five rights of hiring just as nurses use the five
      rights of medication administration.

PMID- 11982130
TI  - Defining lines. Service-line management helps community hospitals draw up a plan
      for a healthy database.
AB  - Before you fully implement a service line model, review these key logistics.

PMID- 11982131
TI  - Achieve cost benefits with innovative care management.
AB  - Progressive care units (PCUs) are fast emerging to help relieve numerous demands
      on the health care industry. Complete this systematic development process to
      ensure a cost-effective startup PCU.

PMID- 11982132
TI  - The magnetic pull. The number of facilities drawn to nursing's highest honor
      continues to grow.
AB  - Second in an ongoing series of articles, discover the major attributes of
      organizations that earn Magnet status through The Magnet Nursing Services
      Recognition Program for Excellence in Nursing Services of the American Nurses
      Credentialing Center.

PMID- 11982133
TI  - Dream weaver.
AB  - Teach caregivers realistic steps to help ICU patients rest and heal.

PMID- 11982134
TI  - E-scribing: more realistic than ever.
AB  - Electronic medication administration and prescription offer caregivers one
      strategy to reduce medication errors. Advances in bar coding, robotics, and
      wireless technology, and sophisticated clinical decision support systems are
      paving the way.

PMID- 11982135
TI  - The numbers game, again?

PMID- 11982136
TI  - Hashing out California's staffing ratios.

PMID- 11982137
TI  - The thrills! The planning! The tireless effort! Utah nurses make their mark at
      Winter Olympics.

PMID- 11982138
TI  - Turning a spotlight on nurses' achievements.

PMID- 11982139
TI  - Environmental health in the health care setting.
AB  - The health care industry is a major contributor to environmental pollution.
      Through the processes of waste disposal, including incineration, the health care
      industry is one of the largest contributors to environmental dioxin and mercury.
      Mercury contamination of our waterways has created the conditions by which a
      significant number of fish are sufficiently mercury-laden so as to pose a human
      health threat. Additionally, there are products and processes within the hospital
      that create health risks for the patients and health care staff. There are a
      number of positive actions that nurses can take to address the health threats
      posed by these exposures. These actions include: purchasing environmentally
      preferable products, implementing pollution prevention actions within the health
      care setting, and learning more about environmental health.

PMID- 11982140
TI  - Striking nurses win from coast to coast.

PMID- 11982141
TI  - No time to be fearless.

PMID- 11982142
TI  - Choosing the right insulin regimen for optimum control.

PMID- 11982143
TI  - Diagnosing and managing fungal skin and nail infections.

PMID- 11982144
TI  - Functional foods--do they have a role in heart health?

PMID- 11982145
TI  - Choosing the right stoma appliance for a colostomy.

PMID- 11982146
TI  - Intrauterine contraception: a look at devices and systems.

PMID- 11982147
TI  - Childhood vaccination programmes: what's new?

PMID- 11982148
TI  - Nurses have helped transform the management of diabetes.

PMID- 11982149
TI  - Treating venous leg ulceration with complementary therapy.

PMID- 11982151
TI  - A tool for managing stroke.

PMID- 11982150
TI  - GOAL trial to determine if asthma control is achievable.

PMID- 11982153
TI  - Flu campaign gets expansion.

PMID- 11982154
TI  - Flu immunisation campaign.

PMID- 11982155
TI  - Assessing and treating nocturnal enuresis in children.

PMID- 11982156
TI  - Giving advice on infant feeding and good weaning practice.

PMID- 11982157
TI  - Guidance on preventing sudden infant death syndrome.

PMID- 11982158
TI  - Prescribing a better quality of life in Parkinson's disease.

PMID- 11982159
TI  - Choosing the right urinary drainage system in incontinence care.

PMID- 11982160
TI  - Safe prescribing and use of the oral contraceptive pill.

PMID- 11982161
TI  - Why wound pain should be accurately assessed.

PMID- 11982162
TI  - Enough flu vaccine for all, says DoH.

PMID- 11982163
TI  - Poor health and poverty 'trap' elderly people.

PMID- 11982165
TI  - Community cancer care gets a boost.

PMID- 11982164
TI  - Polio vaccine recalled.

PMID- 11982166
TI  - Screening and treating those at risk of nutritional deficiency.

PMID- 11982167
TI  - Functional foods--can they provide a cure for ills?

PMID- 11982168
TI  - The role of diet in reducing the risk of osteoporosis.

PMID- 11982169
TI  - 'Tis the season to be jolly ... not too jolly.

PMID- 11982170
TI  - Food for thought in managing inflammatory bowel disease.

PMID- 11982171
TI  - Addressing patients' concerns over inhaled corticosteroids.

PMID- 11982172
TI  - Meeting the manual handling needs of disabled people.

PMID- 11982174
TI  - Developing a formulary for wound dressings.

PMID- 11982173
TI  - Role of lanolin in managing eczema and dry skin conditions.

PMID- 11982175
TI  - A cash boost for tackling heart disease in primary care.

PMID- 11982176
TI  - New therapeutic tool in diabetes management.

PMID- 11982177
TI  - Need for focus on obesity care.

PMID- 11982178
TI  - Osteoporosis strategy for primary care.

PMID- 11982179
TI  - Communicating with physicians.

PMID- 11982180
TI  - Nonfunctional gut? Try a probiotic food.
AB  - This month's Nutrition column discusses the problem of antibiotic-associated
      diarrhea. The overgrowth of the "good" bacteria, Clostridium difficile, can cause
      severe abdominal pain, fever, and diarrhea. This article examines the benefits of
      including probiotics in a meal plan when the use of antibiotics is medically
      indicated.

PMID- 11982181
TI  - Communication skills for telehealth interactions.
AB  - Telehealth technologies provide a challenging new home care approach. Through the
      use of cameras, video display services, and telephone lines, nurses can interact
      with patients located several miles away. In delivering services from a distance,
      the ease of equipment operation and installation, picture, and voice quality are
      important. Of equal importance are the nurse's communication skills in conducting
      telehome visits.

PMID- 11982182
TI  - Pain assessment in patients with dementia and how to use pain scales.

PMID- 11982183
TI  - Hanging wet-to-dry dressings out to dry.
AB  - Wet-to-dry dressings have been standard procedure for home care wound care
      patients although research indicates gauze dressings are not an optimal wound
      care modality for the patient, the clinician, or the healthcare system. Gauze
      dressings do not effectively support optimal healing and are more labor intensive
      to use than advanced dressings such as films, foams, hydrocolloids, and
      hydrogels. This article provides clinicians with the rationale and evidence
      needed to collaborate with physicians in choosing the most cost-effective wound
      care products to achieve positive patient outcomes.

PMID- 11982184
TI  - Calculating your specific dressing costs.

PMID- 11982185
TI  - Helping patients manage cancer-related fatigue.
AB  - Fatigue is the most common side effect of cancer treatment, yet is sometimes
      ignored by healthcare professionals. Home care and hospice nurses work closely
      with patients and families experiencing the overwhelming impact fatigue has on a
      patient's quality of life. This article provides a comprehensive discussion of
      the causes of cancer-related fatigue and the interventions to be considered.

PMID- 11982186
TI  - Cardiac home care programs impact patients after coronary artery bypass grafting.
AB  - Many hospitals have initiated early discharge programs in an effort to transition
      coronary artery bypass grafting patients home as quickly as possible. To meet the
      needs of patients who are discharged early, several home care agencies have
      created special cardiac programs. This article describes the common components of
      six successful home care cardiac programs.

PMID- 11982187
TI  - Evaluating physical therapy utilization under PPS.

PMID- 11982188
TI  - Accidental acts of kindness.

PMID- 11982189
TI  - Clinical experience.

PMID- 11982190
TI  - The prognostication problem.
AB  - With increased focus on end-of-life care; prognosis may be finally receiving the
      attention it deserves. Hopefully, this will result in further research, the
      development of effective tools, and adequate education and training related to
      prognostication.

PMID- 11982191
TI  - Transport and storage of infusion supplies and blood products.
AB  - Home care nurses face many challenges in transporting and storing medications and
      blood products in their vehicles and in patients' homes. Unlike climate
      controlled institutions, products subject to the cold of winter and the heat of
      summer can easily be damaged, which can be harmful to the patient. Additionally,
      several regulations and protocols demand that products be cared for in a certain
      manner, stored in the proper container, and labeled appropriately. The following
      information presents the current practices in storing and transporting these
      products safely. It can be used as a guide for policy and procedure development
      and a review for clinicians in assuring safe handling of these products from
      office to home to lab.

PMID- 11982192
TI  - New Health Care Financing Administration common procedure coding system codes for
      collagen dressings.

PMID- 11982193
TI  - OASIS voice mailbox inservices.
AB  - Assuring accuracy and reliability in OASIS data collection is more than just a
      one-time orientation. This article describes a lively ongoing OASIS educational
      program creatively using the agency's voice mail system. The article presents
      basic OASIS information and is a required reading for clinicians and managers who
      are interested in accurately collecting OASIS data.

PMID- 11982194
TI  - Palliative care: what is it?
AB  - Palliative care developed during the hospice movement. Hospice was associated as
      a rest place for weary travelers in ancient times, many of whom were ill. Hospice
      first became associated with the dying in France in 1842; the first modern
      hospice, St. Christopher's Hospice, was established in London by Dame Cicely
      Saunders in 1967. It was the first facility founded as a "place" to care for the
      dying. In 1974, the first U.S. hospice was established in Connecticut based on a
      home care model. In 1975, Balfour Mount, MD, founded the Palliative Care Service
      in The Royal Victoria Hospital in Montreal; the concept of "palliative care" in
      North America was established (Sheehan & Forman, 1996). The traditional view of
      palliative care indicates that symptomatic and supportive care are generally
      withheld until all attempts to treat the underlying disease and other medical
      problems are exhausted. Many times, palliative care is offered with little time
      left for living. Palliative care should be considered in conjunction with active
      treatment, and, as death nears, palliative care becomes more important as active
      treatment while cure become less important.

PMID- 11982195
TI  - Increasing recognition and referral of the depressed elderly.

PMID- 11982196
TI  - Evolution of a home health ethics committee.
AB  - In 1996, the Visiting Nurse Association of Boston established an Ethics Advisory
      Committee to address ethical issues that arise in patient care. This article
      describes the Committee's development from implementation of an ethics education
      plan for agency staff, to policy recommendations and consultation for ethical
      conflicts in patient care. Whether developing an ethics committee or evaluating
      your current one, this article can be helpful.

PMID- 11982197
TI  - The use of LPNs in Ohio home care agencies.
AB  - A rapid rate of change in the home care arena has been widely documented and many
      more changes are likely to continue. This article presents the results of a
      descriptive study to characterize the use of licensed practical nurses (LPNs)
      within Ohio home care agencies. Among the findings were that that agencies use
      LPNs primarily in medical-surgical cases and that the use of LPNs is expected to
      increase.

PMID- 11982198
TI  - The demise of a psychiatric home care program.

PMID- 11982199
TI  - Psychiatric home care is an asset--not a liability.

PMID- 11982200
TI  - Telehealthcare under PPS: tools to make it work.

PMID- 11982201
TI  - Hospice and palliative nursing competencies published.

PMID- 11982202
TI  - Trisodium citrate anticoagulation therapy.

PMID- 11982203
TI  - Efficient or family-centred? Practitioners' goals in decisions regarding parental
      presence during invasive procedures.
AB  - Little is currently documented about how health care professionals determine when
      parental presence is appropriate during an invasive procedure. The research
      profiled in this article was a qualitative study of the decision-making by 10
      nurses and five physicians in PICU regarding when and how to include parents as
      witnesses to invasive procedures. This article includes one aspect of the
      research findings: practitioners' goals in such decisions. Specifically, the
      authors will detail how practitioners' perspectives about the primacy of
      particular goals of the child's care influenced their decisions to encourage or
      discourage parents from remaining with their children during invasive procedures.
      It was found that participants' decisions whether or not to permit parents to
      remain during invasive procedures were primarily determined by what the
      practitioner held as the priority goal of his/her practice (i.e., efficiency or
      family-centred care). The authors conclude by identifying some clinical and
      research directives that arise from the research findings.

PMID- 11982204
TI  - Transfer stress and medical intensive care patients and family members.
AB  - OBJECTIVE: To explore the phenomenon of transfer stress in medical intensive care
      (MICU) patients and family members. DESIGN: Descriptive study using a cross
      sectional survey. SETTING: Two university-affiliated tertiary care centres in
      western Canada. PARTICIPANTS: Convenience sample of 53 patients and 35 family
      members who were within 48 hours of having experienced transfer from MICU.
      INSTRUMENTS: Perception of transfer as a stressor scale and information received
      related to transfer survey. RESULTS: Over 75% of MICU patients and family members
      experienced moderate to severe transfer stress. Both patients and family members
      reported receiving limited information related to transfer from MICU. The amount
      of information received did not correlate significantly with the level of
      transfer stress in patients or family members. CONCLUSION: Transfer stress
      frequently occurs in MICU patients and family members and should be an area of
      concern for health care professionals.

PMID- 11982205
TI  - A review of neuromuscular blockade in the critically ill patient.
AB  - The continuous administration of neuromuscular blocking agents is thought to be
      associated with a number of adverse effects and complications, including post
      paralytic syndrome (characterized by persistent paralysis), muscle weakness, and
      the inability to wean from the ventilator despite discontinuation of the therapy.
      Consequently, clinical objectives emphasize administering only the dose necessary
      to optimize the effect of the drug and for the shortest possible time. This
      article provides an overview of the administration of neuromuscular blocking
      agents, from the perspective of a critical care pharmacist and critical care
      nurses. The complexities associated with pharmacological paralysis in critically
      ill patients warrants the comprehensive approach to care that multidisciplinary
      team members can provide.

PMID- 11982206
TI  - Advanced nursing skill certification in critical care.
AB  - Advances in critical care therapies demand that registered nurses maintain skills
      consistent with the ability to provide safe patient care. Advanced nursing
      function (ANF) certification is one way to achieve this goal. The purpose of this
      article is to describe the annual certification process that occurs in one
      general systems critical care unit within a large urban acute care setting. Two
      hundred registered nurses are certified annually in cardioversion/defibrillation,
      pacemakers, intraspinal analgesia, pulmonary artery catheters and intracranial
      pressure monitoring. Involving both conceptual and psychomotor skill assessments,
      ANF certification not only challenges educators to possess and maintain current
      knowledge about ANF procedures, but also readily identifies areas of strength and
      weakness for the nurse regarding knowledge and practice development about a
      particular procedure. The critical care education committee recognized the need
      for advanced nursing knowledge in order to provide quality, safe patients care
      and to meet the needs of patients with complex care requirements. ANF
      certification has proved to be an efficient, cost-effective method to educate
      many nurses in a relatively short period of time. Most importantly, ANF
      certification assists to maintain an optimum standard of care within the critical
      care unit and, at the same time, lends itself well to the development of other
      advanced critical care procedures in the future.

PMID- 11982207
TI  - Critical thinking: leading nurses ... forward.

PMID- 11982208
TI  - [Lasers in dentistry 2. Diagnosis of dental caries with lasers].
AB  - When enamel, dentine and substances in caries lesions are exposed to (laser)
      light of a specific colour, fluorescence may be induced. This principle is at the
      basis of two caries diagnostic methods, DIAGNOdent and Quantitative Laser (Light
      induced) Fluorescence (QLF). Only the DIAGNOdent is commercially available.
      Bacterial porphyrins evoke fluorescence when illuminated with red light and the
      intensity of the emitted light is related to the size of the caries lesion.
      Published research indicates that the DIAGNOdent is particularly suitable for
      detecting small bacteria containing caries lesions, and to monitor such lesions.
      QLF is based on the fluorescence decrease in demineralised enamel upon exposure
      to blue-violet (laser) light. The intensity of the emitted light is related to
      the amount of mineral loss in the caries lesion. Using QLF the mineral loss in
      caries lesions can be measured quantitatively. Like the DIAGNOdent, QLF is
      particularly suitable to monitor caries lesions.

PMID- 11982209
TI  - [Double teeth].
AB  - Double teeth are not really rare, but it is still enigmatic why and how they
      develop. Based upon the clinical, morphological and anatomical appearance and the
      number of teeth in mouths with double teeth, the double teeth are labelled as
      products of 'fusion' and 'clefting', but the criteria to attach such etiological
      names are lacking. It is assumed that heredity is involved in the development of
      double teeth. Therefore it is attempted to explain why only one of a homozygotic
      twin had a double tooth.

PMID- 11982210
TI  - [Tooth brushing in babies and toddlers].
AB  - The aim of this study was to investigate tooth brushing in toddlers and children
      younger than 4 years of age and the experiences of their parents. This study was
      performed in 3 towns in the middle of the Netherlands at the Office for Parent
      and Childcare. 99.4% of the children were brushed at least once a day during 0.5
      1 minute. Tooth brushing is considered as a part of daily health care. Most
      children are cooperative and their parents enjoy brushing the teeth of their
      children. 17.5% of all parents experience problems with brushing teeth of their
      toddler or young child; 46% of them would like more information. But as the total
      number of children in a family increases, the parents' pleasure in brushing
      decreases. The Office for Parent and Childcare in the Netherlands has an
      important place in providing information on oral healthcare and especially tooth
      brushing for toddlers and children younger than 4 years of age. It would be
      useful to investigate how these healthcare workers get their dental information.

PMID- 11982211
TI  - [The use of psychoactive remedies by dental students].
AB  - Dutch dental students were investigated for their attitudes, opinions and actual
      use of psychoactive substances such as tobacco, alcohol and drugs. A
      questionnaire from the United States (115 items) was translated and adapted to
      the Dutch situation and subsequently administered to dental students at two
      dental schools in The Netherlands (Academic Centre for Dentistry Amsterdam--ACTA-
      and the University of Nijmegen--KUN). The use of alcohol was very high (lifetime
      95%, past year 94%, past month 88%). No significant correlations were found
      between alcohol use and gender, schools and years. Of the students 17% reported
      getting drunk at least monthly. Prevalence rates for the past month use of
      tobacco was 24% and marijuana 4%. Male students smoked twice as much as female
      students. When asked whether their schools offered policy programmes on alcohol
      and drugs, 52% of the students reported that these were not available. It is
      concluded that schools have to pay more attention to these issues.

PMID- 11982212
TI  - [Foreign body in the maxillary sinus].

PMID- 11982213
TI  - [Gastroenteritis].

PMID- 11982214
TI  - HHN featuring an article written about my needlestick by Jane Perry and Janine
      Jaeger.

PMID- 11982215
TI  - Issues affecting health care workers in home health.

PMID- 11982216
TI  - Patients are being refused around here due to the chronicity of their problem.

PMID- 11982217
TI  - Payment pointers.

PMID- 11982218
TI  - Graduating to smart home health delivery.

PMID- 11982219
TI  - Have politics and regulations contributed to the nursing shortage?

PMID- 11982220
TI  - Using case mix and adverse event outcome reports for outcome-based quality
      monitoring.
AB  - The OBQM process is similar to many of the QI/PI processes that agencies have
      used in the past. The Adverse Event Outcome and Cse Mix Reports, based on OASIS
      data, provide agencies with clinical out come data that can be used to improve
      quality of care. The reposts are a first step in the effort to bring the home
      care industry to a new era of using patient-centered data as the basis for
      improving services.

PMID- 11982221
TI  - Battling bacteria in wound care.
AB  - A critical aspect of effective and cost-efficient wound management is infection
      prevention and actions taken to minimize bacterial levels in the wound. This
      article describes effective wound cleansing and debridement, appropriate use of
      advanced dressings, procedures for dressing changes, and the appropriate use and
      understanding of topical antimicrobial agents.

PMID- 11982222
TI  - Assessing respiratory status from a distance.
AB  - Home care professionals are increasingly required to manage patients with chronic
      respiratory conditions. Under PPS, an even stronger mandate requires that every
      intervention be timely, necessary, valuable, cost effective, and lead to positive
      patient outcomes. This article focuses on the cost benefits, tools, and
      interventions available that enhance the ability to assess respiratory status
      "from a distance."

PMID- 11982223
TI  - Getting started with OBQM: analyzing case mix and adverse events.

PMID- 11982224
TI  - Home health coordination versus discharge planning: where is the line?

PMID- 11982225
TI  - Top secret: for new nurse managers only!

PMID- 11982226
TI  - How the OASIS could include diabetes.

PMID- 11982227
TI  - The medicare part B surgical dressing policy.

PMID- 11982228
TI  - OASIS--the silent partner: have we missed the point?

PMID- 11982229
TI  - The use of high-frequency oscillatory ventilation in adult ARDS patients.
AB  - Current ventilatory objectives for adults with ARDS include maximizing gas
      exchange while minimizing lung injury. To this end, high-frequency oscillatory
      ventilation (HFOV), a mechanical ventilation strategy that simultaneously avoids
      end-inspiratory alveolar overdistension and end-expiratory alveolar collapse, has
      been recommended. HFOV meets these criteria from a theoretical perspective,
      however, is without the benefit of a prospective randomized clinical trial of CMV
      versus HFOV to demonstrate that effect. This article provides an overview of high
      frequency oscillation, followed by an illustration of how it was applied in the
      case of a 43-year-old patient who developed respiratory failure 24 hours post
      Caesarean section.

PMID- 11982230
TI  - Liposomal amphotericin B for the treatment of severe fungal infection.
AB  - Amphotericin B is commonly used in the intensive care unit to treat invasive
      fungal infection. This medication is associated with a number of adverse events
      during infusion, such as fever, rigors, chills, electrolyte disorders and renal
      insufficiency. Liposomal amphotericin B can be used as an alternative to
      conventional amphotericin B to treat fungal infection. Patients receiving
      liposomal amphotericin B experience fewer adverse events than recipients of the
      conventional formulation; moreover, the liposomal formulation has been found to
      be as effective as the conventional amphotericin B to treat specific fungal
      infections. Unfortunately, the pharmacoeconomics of the liposomal formulation has
      limited the use of this medication. The purpose of this article is to present a
      brief summary of conventional amphotericin B with an emphasis on the narrow
      therapeutic index of this antibiotic. The liposomal amphotericin B solution is
      compared to conventional amphotericin B regarding the pharmacokinetics and
      pharmacodynamics. Therapeutic use, tolerability, and pharmacoeconomic
      implications of liposomal amphotericin B are discussed.

PMID- 11982231
TI  - Acute myocardial infarction and the 12-lead ECG.
AB  - It is important that critical care nurses are able to identify the location of
      cardiac muscle ischemia, injury, and infarction on the electrocardiogram. Knowing
      the site of infarction is essential in anticipating clinical manifestations and,
      therefore, has implications for the patient's plan of care. This article includes
      an overview of four sites of infarction: inferior, posterior, anterior, and
      lateral. The coronary artery source of each, as well as the ECG findings and
      clinical signs and symptoms are discussed.

PMID- 11982232
TI  - Critical thinking: position statements: professional tools to support today's
      nurses.

PMID- 11982233
TI  - CACCN's position statement on withholding and withdrawing of life support.

PMID- 11982234
TI  - Caring for staff nurses.

PMID- 11982235
TI  - Fetal monitoring discrepancies.

PMID- 11982236
TI  - AIDS from the beginning.

PMID- 11982237
TI  - Quitting smoking harder for women than for men.

PMID- 11982238
TI  - New JCAHO patient safety standards.

PMID- 11982239
TI  - Newborn abandonment. Finding legislative solutions.

PMID- 11982240
TI  - Managing epidurals.

PMID- 11982241
TI  - Seeking satisfaction. Treating decreased libido in women.

PMID- 11982242
TI  - Teen talk. An intervention for pregnant and parenting adolescents.

PMID- 11982243
TI  - Coming to arms. Calming newborns during heel stick procedures: a Turkish
      perspective.

PMID- 11982244
TI  - Prepping for healthy moms & babies. Making the case for preconception care &
      counseling.

PMID- 11982245
TI  - Shift change. Promoting cultural diversity in the workplace.

PMID- 11982246
TI  - Depression, bone mass and osteoporosis.

PMID- 11982247
TI  - Weight loss and exercise in type 2 diabetes.

PMID- 11982248
TI  - Caring for newborn skin.

PMID- 11982249
TI  - My mother's passing taught about both living & dying.

PMID- 11982250
TI  - Inductions vs. postdates.

PMID- 11982251
TI  - Inductions vs. postdates.

PMID- 11982252
TI  - Breastfeeding promotion.

PMID- 11982253
TI  - Curing & caring.

PMID- 11982254
TI  - Shortages and solutions. Looking closely at nursing workforce issues.

PMID- 11982255
TI  - Women & smoking: the impact.

PMID- 11982257
TI  - Scientists find new tumor suppressor gene.

PMID- 11982256
TI  - Decline in nursing working conditions, quality of care documented.

PMID- 11982258
TI  - Vulvar pain may signal cancer.

PMID- 11982259
TI  - Addressing the nursing shortage.

PMID- 11982260
TI  - Colon cancer in women.

PMID- 11982261
TI  - Genetic advances in bipolar disorder.

PMID- 11982262
TI  - Weighing the risks. Genetic counseling for hereditary breast and ovarian cancer.

PMID- 11982263
TI  - Baby-friendly charting.

PMID- 11982264
TI  - Hyperbilirubinemia.

PMID- 11982265
TI  - New tools to combat obesity.

PMID- 11982266
TI  - AWHONN urges congress to pass nursing legislation.

PMID- 11982267
TI  - Now, I'm 1 out of 8. Living through healing.

PMID- 11982269
TI  - New recommendations for recurrent miscarriage management.

PMID- 11982268
TI  - Promoting breastfeeding.

PMID- 11982270
TI  - Most withdrawn prescription drugs more dangerous to women.

PMID- 11982271
TI  - FDA issues urgent notice of recalled injectable drugs.

PMID- 11982272
TI  - Mother Jones magazine questions cytotec for labor induction.

PMID- 11982273
TI  - Seeking a federal appointment. How ANA is putting nurses to work in Washington.

PMID- 11982274
TI  - Fetal oxygen saturation monitoring. Using this new technology for fetal
      assessment during labor.

PMID- 11982275
TI  - Double-take. Defining the need for specialized prenatal care for women expecting
      twins: a Canadian perspective.

PMID- 11982276
TI  - Induction vs. post-date pregnancies. Exploring the controversy of who's really at
      risk.

PMID- 11982277
TI  - Understanding genetics. Shaping the foundation for future nursing practice.

PMID- 11982278
TI  - Preventing cardiovascular disease.

PMID- 11982279
TI  - Where does a gorilla sleep?

PMID- 11982281
TI  - Combating the nursing shortage.

PMID- 11982280
TI  - Building expertise. Making the case for fetal heart monitoring certification.

PMID- 11982282
TI  - Combating the nursing shortage.

PMID- 11982283
TI  - Exploring advanced directives in the OB setting.

PMID- 11982284
TI  - Diet and exercise dramatically delay type 2 diabetes.

PMID- 11982285
TI  - Bayer voluntarily withdraws Baycol.

PMID- 11982287
TI  - Checking up on cholesterol. New guidelines move ratio relationship.

PMID- 11982286
TI  - Grassroots activism. How nurse practitioners in Virginia harnessed their
      political power.

PMID- 11982288
TI  - Stalking the #1 killer of women ... detecting diabetes & heart disease.

PMID- 11982289
TI  - Tuberculosis in pregnancy. This old disease is presenting new challenges.

PMID- 11982290
TI  - Newborn abandonment. Would you know what to do?

PMID- 11982291
TI  - Coping with bed rest. Moving toward research-based nursing interventions.

PMID- 11982292
TI  - Perinatal teamwork. Turning rhetoric into reality.

PMID- 11982294
TI  - Helping consumers control blood pressure.

PMID- 11982293
TI  - Culturally congruent care in the NICU. Exploring the needs of a Mexican family
      and their infant son.

PMID- 11982295
TI  - Take care of yourself--just for the health of it.

PMID- 11982296
TI  - Stepping back, stepping forward. Woman's health care in Bosnia-Herzegovina.

PMID- 11982297
TI  - Breastfeeding promotion.

PMID- 11982298
TI  - The natural history of ticks.
AB  - Ticks have evolved to become one of the most important groups of arthropod
      vectors of human pathogens. One or more of the approximately 840 known species of
      ticks are found in most terrestrial regions of the earth. Ticks are a highly
      specialized group of obligate, bloodsucking, nonpermanent ectoparasitic
      arthropods that feed on mammals, birds, and reptiles. They are classified into
      two major families, Ixodidae (hard-bodies ticks) and Argasidae (soft-bodied
      ticks). The Ixodidae is the largest and most important family. There are many
      taxonomic keys for identifying ticks to assist the serious investigator. Their
      life cycles are often complex, and even though ticks are associated with their
      parasitic habits, ticks spend most of their life off hosts and in vegetation or
      soil. Maintenance of water balance during periods of overhydration while feeding
      and periods of dehydration while fasting is significant in the distribution,
      survival, activity, and transmission of disease-causing pathogens to humans and
      animals. Ticks attach to skin of the host by using their hypostome as an anchor
      and create a feeding lesion to ingest blood or tissue fluids. Soft-bodied ticks
      feed relatively rapidly (hours or less) and ingest only blood. Hard-bodied ticks
      take days to complete feeding and feed on blood, lymph, and lysed tissues from a
      pool that forms around the mouthparts. Feeding causes direct damage to the skin
      of the host. Disease-causing organisms may be ingested or expelled during
      feeding. Ingestion of relatively enormous quantities of blood is characteristic
      of ticks.

PMID- 11982299
TI  - Prevention of tick-borne diseases.
AB  - Ticks are a part of the landscape where humans live, work, and play. Because
      ticks carry a wide range of organisms that potentially can cause disease in
      humans, many studies have focused on ways to reduce risk of these diseases. Ticks
      have biologically complex interactions with microorganisms and with their
      vertebrate hosts, on whom they depend for blood meals and survival. To consider
      ways to reduce the burden of tick-borne diseases in humans, it is necessary to
      understand the biology and ecology of ticks and their interface with humans. In
      many areas, changes in land use, reforestation, and patterns of human settlements
      have led to more abundant tick populations, increasing rates of infections in
      ticks, and increasing contact with human populations. Warmer winter temperatures
      in temperate regions may extend the transmission season for some ticks and
      pathogens. Although much of the discussion in this article has focused on I.
      scapularis and the Lyme disease spirochete (because they have been studied
      extensively), other tick-pathogen pairs may differ in risk factors for infection
      and transmission dynamics. Interventions studied to reduce the burden of tick
      borne diseases include changing the environment, controlling vertebrate hosts,
      killing ticks, altering the behavior of humans, treating tick bites, and trying
      to protect humans through immunologic means (vaccine). All of these approaches
      have limitations and drawbacks. From a public health perspective, a plan that
      employs multiple strategies may be most effective. This article has reviewed what
      is known about preventive interventions, including the vaccine.

PMID- 11982300
TI  - Erythema migrans.
AB  - EM is the most common manifestation of early Lyme disease, occurring in a high
      percentage of cases. Because this phase of infection with B. burgdorferi offers
      an excellent opportunity to treat this potentially systemic infection, front-line
      physicians must be familiar with its diagnosis. Although much attention has been
      paid to the classic form--the target lesion or bull's eye--there are variations
      that are more common. These include uniform coloration, lesions with necrotic or
      vesicular centers, and lesions with shapes that are not circular or oval. These
      findings must be interpreted in epidemiologic context. Serologic testing at this
      phase of the illness should not be done. It is unnecessary and potentially
      misleading; false-positive and false-negative tests can occur. Diagnosis is
      clinical. Prompt initiation of appropriate antibiotic therapy for 3 weeks cures
      most patients at this early stage of the disease. Clinicians should be aware that
      15% of patients may be coinfected with a second tick-borne pathogen, which could
      alter the usual clinical manifestations and the response to treatment.

PMID- 11982301
TI  - Neurologic aspects of Lyme disease.
AB  - Lyme disease has emerged as a major infection with frequent neurologic
      manifestations. These manifestations probably reflect several predominantly
      indirect pathogenetic mechanisms and involve host, vector, and organism factors.
      With early diagnosis and appropriate antibiotic treatment, patients do well.
      Because culture is not reliable, diagnosis has relied on positive serology to
      document exposure. Serology should improve as second-generation assays become
      available. Although there is a preventive vaccine based on the lipoprotein OspA,
      newer vaccines in development may prove more desirable. Lyme disease provides a
      valuable model to study how infectious pathogens cause neurologic disease.

PMID- 11982302
TI  - Cardiac manifestations of Lyme disease.
AB  - Lyme disease is a vector-borne illness that can affect numerous organ systems
      during the early disseminated phase, including the heart. The clinical course of
      Lyme carditis is usually benign with most patients recovering completely. In rare
      instances, death from Lyme carditis has been reported. The cardinal manifestation
      of Lyme carditis is conduction system disease, which generally is self-limited.
      Heart block occurs usually at the level of the atrioventricular node but often is
      unresponsive to atropine sulfate. Temporary pacing may be necessary in more than
      30% of patients, but permanent heart block rarely develops. Myocardial and
      pericardial involvement can occur but generally is mild and self-limited.
      Diagnosis is made by associating the clinical and historical features of
      borreliosis, such as previous tick bite, EM, or neurologic involvement, with
      electrocardiographic abnormalities and symptoms such as chest pain, palpitations,
      syncope, and dyspnea. Serologic studies and endomyocardial biopsy can support the
      diagnosis in the correct clinical setting, and MR imaging, echocardiography, and
      gallium scanning have utility in selected circumstances. No treatment has been
      shown clearly to attenuate or prevent the development of Lyme carditis, but mild
      carditis generally is treated with oral antibiotics and severe carditis with
      intravenous antibiotics in an effort to eradicate the infection and prevent late
      complications of Lyme disease. There is conflicting evidence regarding the role
      that B. burgdorferi plays in the development and progression of chronic
      congestive heart failure. Because of the significant false-positive ELISA rate in
      this population and the unclear benefit of antibiotic therapy, confirmatory
      Western blot analysis is recommended. Routine therapy and screening of patients
      with idiopathic dilated cardiomyopathy is of limited utility and should be
      reserved for patients with clear history of antecedent Lyme disease or tick bite.

PMID- 11982303
TI  - Lyme arthritis.
AB  - Infection with B. burgdorferi can cause a large joint inflammatory arthritis in
      patients who have not been treated for early Lyme disease; the knee is the most
      common joint affected. The diagnosis depends on a history of known exposure to
      the spirochete, characteristic clinical features, and serologic studies (ELISA
      and Western blot) confirming exposure to the spirochete. In most patients,
      antibiotic therapy is curative, but in a smaller percentage of patients, the
      presence of the HLA-DR beta 1*0401 haplotype can trigger treatment-resistant
      arthritis, in which antibiotic therapy is ineffective; in these instances,
      remittive agents, such as hydroxychloroquine and methotrexate, are indicated.
      Arthroscopic synovectomy may be considered when antibiotic therapy is not
      curative. Fibromyalgia can follow infection with B. burgdorferi but is
      unresponsive to antibiotic therapy; it is treated with tricyclic antidepressants
      and an exercise program. Lyme arthritis is the only chronic inflammatory
      arthritis in which the specific cause is known and can be cured. As such, it
      serves as an excellent model with which to study the pathogenesis of more common
      inflammatory arthritides, such as rheumatoid arthritis.

PMID- 11982305
TI  - Late and chronic Lyme disease.
AB  - This article reviews the late and chronic manifestations of Lyme disease. Special
      attention is given to the chronic manifestations of the disease, detailing its
      pathogenesis, clinical spectrum, and laboratory criteria for the diagnosis. Based
      on experimental evidence and experience, approaches to the successful treatment
      of the late and chronic disease are outlined. Much additional work is needed to
      improve the understanding of the underlying pathophysiology of the disease, its
      diagnosis and treatment.

PMID- 11982304
TI  - Laboratory testing for suspected Lyme disease.
AB  - Laboratory testing for B. burgdorferi infection is intended to substantiate a
      physician's clinical judgment of whether a patient has Lyme disease or not.
      Cultivation of B. burgdorferi from a patient's skin or blood is the gold standard
      for demonstration of active infection, but it is expensive and lacks clinical
      sensitivity. Detection of spirochetal DNA in clinical samples by PCR has better
      sensitivity, but PCR for B. burgdorferi has not yet been standardized for more
      routine diagnostic testing. Detection of antibodies to B. burgdorferi is the most
      practical and common approach for laboratory work-up of a case of suspected Lyme
      disease. Serologic assays fall short of 100% sensitivity and specificity,
      however, and examination of a single specimen in time does not discriminate
      between previous and ongoing infection. Because of a background false positivity
      even among healthy populations of nonendemic regions, serologic testing is
      recommended only when there is at least a one in five chance, in the physician's
      estimation, that the patient has active Lyme disease. The pretest likelihood of
      the disease is determined by the physician in the context of epidemiologic and
      clinical facts of the case. This estimate can serve to reassure patients who are
      at low risk of B. burgdorferi infection but are seeking a Lyme test for
      complaints of a more nonspecific nature. Although new subunit serologic assays
      based on recombinant proteins are becoming available commercially, the
      longstanding two-test approach, in which a positive or indeterminate result with
      a standardized, sensitive ELISA test is followed by verification with a more
      specific Western blot assay, still provides the physician with a reasonably
      accurate and reliable assessment of the presence of antibodies to B. burgdorferi.
      More recent challenges for serologic testing are seropositivity in the population
      as the result of immunization with the Lyme disease vaccine and the emergence of
      new Borrelia species that cause Lyme disease-like illnesses.

PMID- 11982306
TI  - Rocky mountain spotted fever.
AB  - Rocky mountain spotted fever (RMSF) is a fulminant tick-borne infection by
      Rickettsia rickettsii. The classical diagnostic triad is fever, headache and rash
      in a patient with a recent tick bite. With prompt, appropriate antimicrobial
      therapy, patient outcomes are excellent. However, RMSF is often misdiagnosed,
      particularly during the initial stages of illness, and as a result, patient
      outcomes are sometimes suboptimal.

PMID- 11982307
TI  - Babesiosis.
AB  - Babesiosis is an emerging infection caused by protozoal parasites and transmitted
      by the same tick that transmits Lyme disease. Babesiosis is found throughout the
      world, but most cases have been described from the northeastern and northern
      midwestern United States. Patients experience a flulike illness that usually
      lasts for 1 or 2 weeks but may require hospital admission. Those at greatest risk
      of fatal disease include individuals older than age 50 years; asplenic
      individuals; and immunocompromised individuals as a result of immunosuppressive
      drugs, malignancy, or HIV infection. Specific diagnosis is made through
      examination of a Giemsa-stained thin blood smear, DNA amplification using
      polymerase chain reaction, or detection of specific antibody. Treatment consists
      of clindamycin and quinine or atovaquone and azithromycin and, in severe cases,
      exchange transfusion.

PMID- 11982308
TI  - Human ehrlichioses.
AB  - Human ehrlichioses represent one of the best examples of newly emergent
      infectious diseases in which the classic triad of host, infectious agent, and
      environment are intertwined closely. These pathogens have existed for eons on the
      planet, and some were described as veterinary pathogens decades ago. Because of
      dramatic increases of deer and small mammal populations in certain areas and the
      subsequent increased populations of particular blood-feeding ticks, the risk of
      developing these diseases is higher than before. Increasing human populations in
      suburban areas and increased immunosuppressed populations (transplant patients,
      human immunodeficiency virus patients, and cancer survivors) also have increased
      risk of developing severe forms of these diseases.

PMID- 11982309
TI  - Tularemia and Q fever.
AB  - The zoonotic infections caused by Francisella tularensis and Coxiella burnetii,
      tularemia and Q fever, respectively, are two less commonly encountered clinical
      illnesses that are becoming increasingly recognized as epidemiologically
      important human diseases. The prevalence of tularemia and Q fever can be
      positively impacted by increased awareness of the clinical entities that arise
      from infection by these arthropod-borne organisms. Improved recognition of these
      clinical syndromes will lead to greater diagnostic accuracy in recognizing these
      diseases in patients. Ultimately, more stringent measures to prevent infection
      may be required, through raising public awareness, since current therapeutic
      regimens for these two diseases are limited, and knowledge of the pathogenesis of
      these two organisms are still in developing stages.

PMID- 11982310
TI  - Tick-borne relapsing fever in North America.
AB  - Relapsing fever is characterized by recurring episodes of fever and nonspecific
      symptoms (e.g., headache, myalgia, arthralgia, shaking chills, and abdominal
      complaints). The illness is caused by an infection from the Borrelia species
      (spirochetes) that may be acquired through the bite of an infected tick
      (Ornithodoros species) or contact with the hemolymph of an infected human body
      louse (Pediculus humanus). In North America, most cases have been acquired in the
      western United States, southern British Columbia, and few cases have been
      reported from Mexico. Most cases have been acquired from exposure to rustic tick
      infested cabins and caves. This article reviews relapsing fever, especially tick
      borne relapsing fever in North America.

PMID- 11982311
TI  - Colorado tick fever.
AB  - Colorado tick fever, also known as mountain fever and mountain tick fever, is a
      well-described, viral, tick-borne disease common to the Rocky Mountain region of
      the United States and Canada. The Rocky Mountain wood tick, Dermacentor
      andersoni, is the primary vector. The triad of high fever, severe myalgia, and
      headache is typical, but not specific. Although a self-limited disease in most
      cases, severe complications may occur. PCR techniques have been developed that
      allow the diagnosis to be established from the first day of symptoms. Ribavirin
      may merit consideration in the appropriate clinical setting.

PMID- 11982312
TI  - Tick paralysis.
AB  - Tick paralysis is a preventable cause of morbidity and death that, when diagnosed
      promptly, requires a simple low-cost intervention. The key to success is to
      consider tick paralysis in the differential diagnosis of ascending weakness,
      particularly in children, in geographic areas where this disease predominates.

PMID- 11982328
TI  - A model for regulation of ColE1-like plasmid replication by uncharged tRNAs in
      amino acid-starved Escherichia coli cells.
AB  - It has been previously observed that various ColE1-like plasmids replicate
      differentially in Escherichia coli cells during the relaxed response to amino
      acid starvation. Here we develop a kinetic model to explain these observations
      based on the possibility of interaction of the 3' CCA-OH sequence with the UGG
      triplets in loops of RNA I and RNA II encoded by ColE1-like plasmids. According
      to our model, when the interaction of uncharged CCA with RNA I is possible, the
      replication of the ColE1-like plasmid is affected by differences in the
      concentration of various tRNAs in the starved cell, but it is not affected by the
      tRNA concentration if the hypothetical pairing occurs between the CCA-OH and RNA
      II. Using the previously determined parameters for the pBR322 plasmid, the
      concentration of uncharged tRNAs in the amino acid starved relaxed strains and
      the assumed efficiency of binding of tRNA and RNA I, we show that our model
      explains the differences in pBR322 copy number in the relaxed strain starved for
      several amino acids.

PMID- 11982329
TI  - Construction of a plasmid containing human SMN, the SMA determining gene, coupled
      to EGFP.
AB  - We describe here the construction of plasmid pEGFP-C3/SMN, bearing the human SMN
      gene coupled to the green fluorescent protein (GFP) sequence. The mutation of the
      SMN gene is responsible for spinal muscular atrophy (SMA), a frequent human
      infantile genetic disease. We introduced the SMN cDNA into the multiple cloning
      site of pEGFP-C3. This plasmid bears the neomycin-resistance sequence and the
      enhanced green fluorescent protein (EGFP). It results in the expression of a
      fusion protein bearing SMN coupled to a carboxy-terminal GFP tag, used for
      fluorescence localization studies. Transfection of primary human myoblasts with
      pEGFP-C3 or pEGFP-C3/SMN revealed that EGFP is intracellularly localized within
      the cytosol as well as in the nucleus, while the fusion protein EGFP-SMN
      localized within the nucleus in prominent dot-like structures termed "gems."
      These data demonstrate that human primary muscle cells can be efficiently
      transfected and may have important implications for the development of
      therapeutic strategies in SMA.

PMID- 11982330
TI  - pMH11, A tool for gene disruption and expression analysis in Azorhizobium
      caulinodans.
AB  - Tools for mutagenesis and expression analyses are needed to study the role of
      bacterial genes. Here, we report the construction of pMH11, a small, mobilizable
      plasmid that replicates in Escherichia coli, but not in Azorhizobium caulinodans,
      a nodulating microsymbiont of Sesbania rostrata, and that contains a unique BamHI
      restriction site upstream of a promoterless lacZ gene. pMH11 and two derivatives
      with the multiple cloning site of pBluescript (KS(II)) are useful for mutagenesis
      by gene disruption and for expression analyses after selection for cointegration
      by kanamycin resistance. Weakly constitutive promoter activity from the vector
      allowed transcription of genes downstream of the integration site, so that no
      polar effects were caused by gene disruption.

PMID- 11982331
TI  - Selective fitness of four episomal shuttle-vectors carrying HIS3, LEU2, TRP1, and
      URA3 selectable markers in Saccharomyces cerevisiae.
AB  - A comparison of the selective fitness of four 2-microm-based shuttle-plasmids
      carrying the yeast genes HIS3, LEU2, TRP1, and URA3 was performed. The effect of
      each marker on long-term growth rate and plasmid maintenance was measured. In
      selective medium, the LEU2 and URA3 plasmids were maintained at the lowest and
      the highest levels, respectively, while the HIS3 and TRP1 plasmids were
      maintained at an intermediate level. In synthetic complete medium, plasmid loss
      rate was lower for the genes TRP1 and URA3 than for the other two markers, and a
      similar pattern was observed for cells growing in rich medium. These results were
      confirmed by competition experiments among transformants with different plasmids
      in complete and rich media, indicating a different degree of fitness for the
      markers used. A potential correlation of the energy cost of plasmid maintenance
      with the secondary DNA structure and the level of expression of the selective
      markers is also investigated.

PMID- 11982332
TI  - Attenuated Salmonella enterica serovar typhi live vector with inducible
      chromosomal expression of the T7 RNA polymerase and its evaluation with reporter
      genes.
AB  - Attenuated Salmonella strains with defined gene deletions have been extensively
      evaluated as suitable live carriers of passenger antigens. A number of strategies
      for antigen delivery by these strains have been attempted, ranging from plasmid
      based to chromosomal integration systems. We report here the chromosomal
      integration of the T7 RNA polymerase gene (T7pol) in the attenuated strain
      Salmonella enterica serovar Typhi (Salmonella typhi) CVD908 (aroC(-), aroD(-)).
      The T7pol gene was amplified by PCR from Escherichia coli BL21(DE3) and cloned in
      the pNir3 plasmid under the control of the anaerobically inducible nirB promoter.
      Then it was subcloned in a pKTN701 derivative, suicide plasmid with the R6K ori,
      and flanked by the aroC gene. After evaluation of its functionality in E. coli
      SY327, the aroC-T7pol-aroC cassette was integrated into the aroC locus of S.
      typhi CVD908 by homologous recombination. The resulting strain, S. typhi CVD908
      T7pol, was able to transcomplement two plasmids bearing the luc or the lacZ
      reporter genes controlled by the T7 promoter and produce luciferase and beta
      galactosidase under anaerobic culture conditions. Therefore, an inducible system
      for recombinant antigen production in attenuated S. typhi was achieved.

PMID- 11982333
TI  - Inhibition of DNA replication by berenil in plasmids containing Poly(dA)poly(dT)
      sequences.
AB  - The effect of berenil on plasmid DNA replication was studied on pBR322-derived
      plasmids containing poly(dA)poly(dT) sequences. In comparison to the parental
      plasmid pBR322, plasmid pKH47 harboring 100 bp of poly(dA)poly(dT) at the PvuII
      site showed a decrease in plasmid yield in the presence of berenil. This effect
      was also observed in pVL26, a related plasmid in which the location of the
      poly(dA)poly(dT) region had been shifted to the EcoRV site in pBR322.
      [(3)H]Thymidine incorporation experiments indicated that DNA synthesis may be
      affected in these plasmids in the presence of the drug. Bromodeoxyuridine
      incorporation experiments coupled to Cs(2)SO(4) equilibrium density gradient
      centrifugation indicated that the lower plasmid yield was due to an inhibition of
      DNA replication by berenil. We have also found that berenil induces DNA
      degradation in plasmids containing the homopolymer. Our studies strongly suggest
      that the effect of berenil on plasmid replication and DNA stability results from
      its binding to the poly(dA)poly(dT) region present in these plasmids. Moreover,
      we have found a correlation between the position of the poly(dA)poly(dT) region
      and this inhibitory effect. Thus, plasmid pKH47, containing the poly(dA)poly(dT)
      region most proximal to the origin of pBR322 replication, was most severely
      affected.

PMID- 11982334
TI  - Construction of mini-Tn4001tet and its use in Mycoplasma gallisepticum.
AB  - The Mollicutes are a group of cell-wall-less bacteria and are important plant and
      animal pathogens. Progress toward analyzing their pathogenic mechanisms has been
      hampered by the few available genetic tools. Of the two transposons shown to
      function in mycoplasmas, only Tn4001 is readily amenable to modification and
      development. One disadvantage of using Tn4001 in mycoplasmas has been independent
      insertion of the insertion sequence, IS256, probably as a result of inadequate
      control of the transposase expression in mycoplasmas. In this study, we describe
      the construction of a mini-Tn4001 containing the tetM antibiotic resistance gene
      from Tn916. The transposase gene was placed outside the inverted repeats to lower
      the frequency of independent transposition events. Transposition of mini
      Tn4001tet in Mycoplasma gallisepticum occurred at a frequency of 1-8 x 10(-6), a
      frequency similar to that of the parent transposon. Insertions of mini-Tn4001tet
      were random and only single insertions were observed. Several unique restriction
      sites between the inverted repeat sequences provide for further development of
      mini-Tn4001.

PMID- 11982335
TI  - Parameters associated with cloning in Actinobacillus actinomycetemcomitans.
AB  - Characterization of virulence traits in Actinobacillus actinomycetemcomitans
      requires the application of recombinant DNA techniques. To develop appropriate
      genetic tools it is necessary to identify suitable host-vector systems. The
      current study assessed cloning parameters in A. actinomycetemcomitans for two
      previously described vectors, pDMG4 and pMMB67. It was determined that the
      maximum size of recombinant molecules that could be transferred to A.
      actinomycetemcomitans strain ATCC29522 via electroporation was 33 kb. The size
      limit for transformation of the same strain with ligation mixtures (direct
      cloning), however, was limited to 23-24 kb. Additional experiments included
      electroporation of various A. actinomycetemcomitans strains with plasmid DNA
      isolated from Escherichia coli and different A. actinomycetemcomitans sources.
      Differences in transformation efficiencies suggested the presence of a
      restriction modification system for pDMG4 in some strains of A.
      actinomycetemcomitans. Cloning of portions of the enterococcal plasmid pJH1 into
      A. actinomycetemcomitans resulted in the insertion of the intact vector into the
      chromosome.

PMID- 11982336
TI  - Complete DNA sequence and analysis of a mitochondrial plasmid in the
      mycoparasitic Trichoderma harzianum strain T95.
AB  - A circular plasmid called pThr1, with a monomer size of 2.6 kb, was identified in
      the mitochondria of a Trichoderma harzianum isolate. Hybridization studies using
      cloned plasmids revealed no DNA sequence similarity between the plasmid and the
      mitochondrial genome of the isolate. The complete sequence of the plasmid was
      determined, and the sequence analysis revealed that it contained a single long
      open reading frame of 1818 bp. Sequence comparisons indicated that the derived
      amino acid sequence of the ORF exhibited similarity to the reverse transcriptases
      of the circular Mauriceville and Varkud retroplasmids of Neurospora spp. and the
      linear pFOXC2 and pFOXC3 retroplasmids of Fusarium oxysporum strains. In the
      regions of homology all of the seven conserved amino acid blocks characteristic
      of RTs could be found.

PMID- 11982337
TI  - DNA sequence and functional analysis of Lactobacillus delbrueckii subsp. lactis
      plasmids pN42 and pJBL2.
AB  - The plasmids pN42 and pJBL2 were isolated from the Lactobacillus delbrueckii
      subsp. lactis strains NCC88 and JCL414. DNA sequence determination and
      bioinformatic analysis revealed a strikingly conserved genetic organization
      containing five major, highly conserved open reading frames (ORFs).
      Transformation studies indicated that ORF2 (consisting of a primase fused to a
      replicative DNA helicase), ori, and ORF3 constitute the minimal requirements for
      replication of pN42 in the heterologous host Lactococcus lactis. The ORF1's are
      predicted to encode type I restriction-modification (R-M) system HsdS subunits
      with different specificities on either plasmid, suggesting that these plasmids
      may be involved in host defense by expanding their host R-M system repertoire.
      These plasmids constitute the basis for the construction of novel L. delbrueckii
      vectors.

PMID- 11982339
TI  - Highly efficient separation of lithium chloride from seawater.
AB  - A complexing reagent composed of two bipyridine moieties enabled the efficient
      separation of lithium chloride through liquid membrane from seawater, in which
      0.005% lithium chloride is contained (more than 99% metal chlorides are NaCl,
      KCl, MgCl2, and CaCl2). That is, two separations by our liquid membrane changed
      the molar ratio of LiCl from 0.005% to 80%. The striking characteristic of this
      compound is that the lithium ion is separated efficiently from alkali and
      alkaline earth metal ions without the lipophilic anion. Thus this new membrane
      system contructed by us offers a low-energy, low-cost, and environmentally
      friendly method to enable the routine use of lithium chloride separation from
      seawater.

PMID- 11982338
TI  - Arrayed primer extension computing with variant mRNA splice forms. Multiple
      isoforms of CD44 in a human breast tumor.
AB  - The analysis of RNA splicing is important to understanding the diversity in
      protein sequences at specific disease loci, in the immune response, and across
      the proteome. The presence of each exon in a mature mRNA formed from a genomic
      sequence of n exons can be represented by a Boolean variable, enabling mRNA
      structure to be encoded by an n-bit binary number. The CD44 locus has been
      studied as an example of a variantly spliced RNA. Microarray methods can be used
      to address RNA splicing provided they exhibit high fidelity. Our previous work
      showed that the arrayed primer extension (APEX; single-nucleotide polymerase
      extension of microarrays of DNA primers) method gives high-fidelity, digital
      detection of nucleic acid sequences, and it has been used for the solution of
      Boolean computing problems. APEX was adapted to RNA analysis by the use of
      reverse transcriptase and arrays of primers specific to each exon in the CD44
      locus. "Splicotypes" were readily assigned for a number of variant RNA templates.
      Because CD44 is known to be aberrantly spliced in a number of cancers, the RNA
      APEX method with a CD44 microarray was applied to samples from primary tumors of
      individual patients. Up to four different splicing forms of CD44 were detected,
      whereas there have been no previous reports of the presence of more than two CD44
      isoforms within the same tissue.

PMID- 11982340
TI  - Direct measurement of excited-state intervalence transfer in [(tpy)Ru(III)(tppz(*
      ))Ru(II)(tpy)](4+) by time-resolved near-infrared spectroscopy.
AB  - Extension of time-resolved infrared (TRIR) measurements into the near-infrared
      region has allowed the first direct measurement of a mixed-valence band in the
      metal-to-ligand charge transfer (MLCT) excited state of a symmetrical ligand
      bridged complex. Visible laser flash excitation of [(tpy)Ru(tppz)Ru(tpy)]4+ (tppz
      is 2,3,5,6-tetrakis(2-pyridyl)pyrazine; tpy is 2,2':6',6' '-terpyridine) produces
      the mixed-valence, MLCT excited state [(tpy)RuIII(tppz*-)RuII(tpy)]4+* with the
      excited electron localized on the bridging tppz ligand. A mixed-valence band
      appears at numax = 6300 cm-1 with a bandwidth-at-half- maximum, Deltanu1/2 = 1070
      cm-1. In the analogous ground-state complex, [(tpy)Ru(tppz)Ru(tpy)]5+, a mixed
      valence band appears at numax = 6550 cm-1 with Deltanu1/2 = 970 cm-1 which allows
      a comparison to be made of electronic coupling across tppz0 and tppz*- as
      bridging ligands.

PMID- 11982341
TI  - Aqueous room temperature metal-catalyzed living radical polymerization of vinyl
      chloride.
AB  - This paper describes the room-temperature living radical polymerization (LRP) of
      vinyl chloride in H2O/THF in the presence of Cu0 or CuI salts as catalysts, tren
      or PEI as ligands, and iodoform as initiator. The disproportionation reaction
      2CuI + L --> Cu0 + CuII(L) is the crucial step, as it continuously provides the
      active species for both the initiation (Cu0) and the reversible termination step
      (CuII). Mn was found to increase linearly with conversion and is in good
      agreement with Mth, with the Mw/Mn being approximately 1.5.

PMID- 11982342
TI  - One-step synthesis and structure of an oligo(spiro-orthocarbonate).
AB  - The reaction of pentaerythritol and tetraethylorthocarbonate at 260 degrees C for
      12 h yields a white crystalline material that was characterized by 13C CPMAS NMR,
      CHN analysis, FT-IR, electron and X-ray powder diffraction, and Rietveld
      analysis. The white crystalline material was found to have the formula C6H8O4 and
      a crystal structure with a monoclinic cell [a = 9.167 A, b = 5.681 A, c = 5.880
      A, beta = 90.0 degrees , space group I2] of hexagonally arranged spiro-oligomeric
      chains.

PMID- 11982343
TI  - C-C and C-H bond activation reactions in N-heterocyclic carbene complexes of
      ruthenium.
AB  - Thermolysis of Ru(PPh3)3(CO)H2 with the N-heterocyclic carbene bis(1,3-(2,4,6
      trimethylphenyl)imidazol-2-ylidene) (IMes) results in C-C activation of an Ar-CH3
      bond in one of the mesityl rings of the carbene ligand. Upon addition of IMes to
      Ru(PPh3)3(CO)H2 at room temperature in the presence of an alkene, C-H bond
      activation is observed instead. The thermodynamics of these C-C and C-H cleavage
      reactions have been probed using density functional theory.

PMID- 11982344
TI  - A parallel approach to the discovery of carrier delivery vehicles to enhance
      antigen immunogenicity.
AB  - As part of an ongoing effort to generate human and murine monoclonal antibodies
      against poorly immunogenic tumor-associated antigens we have merged the rapidly
      expanding disciplines of parallel polymer synthesis and controlled-release
      technology with immunology to produce a rapid and generic approach to improve the
      immunogenicity of carrier-bound antigens. The process involves three stages: An
      array of cross-linked hydrogel materials containing a carrier protein (at various
      concentrations) is prepared in parallel in one step. The array is then screened
      in mice to determine the most effective hydrogel at enhancing the immunogenicity
      of the encapsulated versus nonencapsulated carrier. Finally, the most efficient
      hydrogel is prepared containing the critical carrier-antigen conjugate and is
      used for immunization protocols. The strategy was successful for the BSA
      glycoconjugate of the tumor-associated antigen GM3 analogue 4. When encapsulated
      within the hydrogel array member most efficient at elevating BSA immunogenicity,
      the BSA-4 glycoconjugate was significantly more immunogenic that when
      administered as a free antigen.

PMID- 11982345
TI  - alpha-1,4-Glucan lyase performs a trans-elimination via a nucleophilic
      displacement followed by a syn-elimination.
AB  - alpha-Glucan lyase (EC 4.2.2.13, GLase) cleaves alpha-1,4-glucosidic bonds via an
      elimination reaction to produce 1,5-d-anhydrofructose. GLase was inactivated by
      the mechanism based alpha-glucosidase inactivator, 5-fluoro-beta-l-idosyl
      fluoride. The trapped glycosyl-enzyme intermediate was isolated and the
      nucleophilic amino acid residue (Asp 553) identified is equivalent to the residue
      so identified in sequence-related alpha-glucosidases. This intermediate undergoes
      a syn-elimination reaction to release the product. Further evidence against a
      direct trans-elimination mechanism was provided by the absence of a primary
      kinetic isotope effect on the substrate substituted with deuterium at the C2
      position.

PMID- 11982346
TI  - Asymmetric synthesis of epicylindrospermopsin via intramolecular nitrone
      cycloaddition. Assignment of absolute configuration.
AB  - A synthesis of (-)-epicylindrospermopsin (2) was completed that establishes its
      absolute configuration and corroborates the corrected structural assignment
      previously made to this toxin by Weinreb et al. The hydroxylamine 3, prepared
      from 4-bromobenzyloxyacetaldehyde, was condensed with aldehyde 4, obtained in
      nine steps from (R)-methionine, to give nitrone 16. Intramolecular cycloaddition
      of 16 proceeded stereoselectively to yield the oxazabicyclo[2.2.1]heptane 17,
      which after reduction and deprotection afforded piperidine 18. The latter was
      transformed via cyclic urea 19 to the inverted C12 alcohol 20, and the derived
      azide 22 was cyclized to produce the guanidine moiety of 25. Final sulfation of
      the C12 hydroxyl group furnished (-)-2.

PMID- 11982347
TI  - Highly effective chiral ortho-substituted BINAPO ligands (o-BINAPO): applications
      in Ru-catalyzed asymmetric hydrogenations of beta-aryl-substituted beta
      (acylamino)acrylates and beta-keto esters.
AB  - A novel family of chiral ortho-substituted BINAPO ligands (o-BINAPO) were
      synthesized from BINOL, and their Ru complexes were highly efficient catalysts
      for asymmetric hydrogenation of beta-aryl-substituted beta-(acylamino)acrylates
      and beta-aryl-substituted beta-keto esters. The Ru-bisphosphinite catalysts can
      tolerate an E/Z mixture of beta-aryl-substituted beta-(acylamino)acrylates. These
      highly enantioselective hydrogenations provide a useful way to prepare beta-aryl
      substituted beta-amino acids and beta-hydroxyl acids.

PMID- 11982348
TI  - A recyclable chiral Ru catalyst for enantioselective olefin metathesis. Efficient
      catalytic asymmetric ring-opening/cross metathesis in air.
AB  - The synthesis and structure of a new chiral bidentate imidazolinylidene ligand
      and a derived chiral Ru-based carbene are disclosed. The Ru complex is
      stereogenic at the metal center; it can be prepared in >98% diastereoselectivity
      and purified by silica gel chromatography with undistilled solvents. The air
      stable Ru complex efficiently catalyzes ring-closing and ring-opening metathesis
      and is recyclable. The chiral complex is highly effective (0.5-10 mol % loading)
      in promoting enantioselective ring-opening/cross metathesis reactions (up to >98%
      ee). These enantioselective transformations can be effected in air, with
      unpurified solvent and with substrates that would only polymerize with Mo-based
      catalysts.

PMID- 11982349
TI  - Total synthesis of (-)-laulimalide.
AB  - (-)-Laulimalide (1), a structurally novel macrolide isolated in trace amounts
      from marine sponges, promotes abnormal tubulin polymerization and apoptosis in
      vitro, with a similar mode of action to that of Taxol(R), but with potentially
      less susceptibility to multidrug resistance. Herein, a flexible and convergent
      asymmetric synthesis of (-)-laulimalide is described. This synthesis featured a
      highly diastereoselective Sakurai reaction of 2 with 3 and a regioselective
      macrolactonization of an unprotected vicinal diol. Laulimalide was synthesized in
      25 steps (longest linear; 36 overall) in 3.5% overall yield, providing a uniquely
      short and efficient route to 1 and its analogues.

PMID- 11982350
TI  - Novel spherical assembly of gold nanoparticles mediated by a tetradentate
      thioether.
AB  - The ability to construct three- and two-dimensional architectures via nanoscale
      engineering is important for emerging applications of nanotechnology in sensors,
      catalysis, controlled drug delivery, microelectronics, and medical diagnostics.
      In this paper, we report novel 3D assembly using multidentate molecular building
      blocks. It is demonstrated that the interparticle linking of gold nanoparticles
      (3.7 nm core size) by a tetradentate thioether, tetra[(methylthio)methyl]silane,
      leads to the formation of a spherical assembly. The spherical size (30-80 nm
      diameter) is dependent on reaction time and relative ratio of the building
      blocks. The novelty of this approach is the viability of multidentate thioethers
      to link nanoparticles and produce spherical assemblies that can be readily
      assembled and disassembled. The spherical assembly can also be partially "melted"
      depending on the nature of interfacial interactions between the assembly and the
      substrate. These unusual morphological properties in shape and surface
      interaction and the intriguing assembling-disassembling capabilities may form the
      basis of designing and fabricating novel functional nanostructures.

PMID- 11982351
TI  - Aromatic 4-tetrahydropyranyl and 4-quinuclidinyl cations. Linking Prins with Cope
      and Grob.
AB  - The chair 4-tetrahydropyranyl cation and the 4-quinuclidinyl cation are shown to
      be energy minima and to be delocalized, with exceptionally long CH2CH2 bonds,
      according to B3LYP/6-31G* calculations; the implications for Prins cyclizations,
      Cope rearrangements, and Grob fragmentations are discussed.

PMID- 11982352
TI  - Diastereocontrolled synthesis of dinucleoside phosphorothioates using a novel
      class of activators, dialkyl(cyanomethyl)ammonium tetrafluoroborates.
AB  - A novel class of activators, dialkyl(cyanomethyl)ammonium tetrafluoroborates 1a
      c, has been developed and applied to the condensations of diastereopure 5'-O-tert
      butyldiphenylsilylthymidine 3'-cyclic phosphoramidites 3a-d with 3'-O-tert
      butyldimethylsilylthymidine (4a). Among them, the condensation of 3a with 4a in
      the presence of 1a completed within 5 min and gave only one diastereoisomer of
      the corresponding phosphite 5a. After sulfurization and deprtection, almost
      diastereopure (Rp)-TpsT 7 was obtained (d.r. = 99:1). Next the 5'-O
      (DMTr)nucleoside 3'-phosphoramidites 8a-d containing thymine, N6-benzoyladenine,
      N4-benzoylcytosine, and N2-phenylacetylguanine have been synthesized and allowed
      to condense with 3'-O-protected thymidine and 2'-deoxyadenosine. The 5'-O-DMTr
      group and the N-acyl groups of the nucleobases were compatible with the reaction
      conditions and the condensations completed quickly with excellent
      diastereoselectivity.

PMID- 11982353
TI  - A simple technique for determining nuclear quadrupole coupling constants with
      RAPT solid-state NMR spectroscopy.
AB  - An enhanced Rotor Assisted Population Transfer (RAPT) experiment is presented and
      used as a simple and fast technique to measure the magnitude of the nuclear
      quadrupolar coupling constant of half-integer quadrupolar nuclei. The enhanced
      RAPT sequence consists of a train of Gaussian pulses with alternating off
      resonant frequencies of +/-nuoff. Simulated and experimental results
      demonstrating the method are given in the case of 87Rb (spin 3/2) and 27Al (spin
      5/2) nuclei. The RAPT sequence is also used to selectively suppress resonances
      based on their quadrupolar coupling constant.

PMID- 11982354
TI  - Identification of iron(III) peroxo species in the active site of the superoxide
      reductase SOR from Desulfoarculus baarsii.
AB  - The active site of superoxide reductase SOR consists of an Fe2+ center in an
      unusual [His4 Cys1] square-pyramidal geometry. It specifically reduces superoxide
      to produce H2O2. Here, we have reacted the SOR from Desulfoarculus baarsii
      directly with H2O2. We have found that its active site can transiently stabilize
      an Fe3+-peroxo species that we have spectroscopically characterized by resonance
      Raman. The mutation of the strictly conserved Glu47 into alanine results in a
      stabilization of this Fe3+-peroxo species, when compared to the wild-type form.
      These data support the hypothesis that the reaction of SOR proceeds through such
      a Fe3+-peroxo intermediate. This also suggests that Glu47 might serve to help
      H2O2 release during the reaction with superoxide.

PMID- 11982355
TI  - Iron and ruthenium Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition
      reactions between nitrones and enals.
AB  - The single coordination-site transition metal Lewis acids [CpM(BIPHOP-F)][SbF6]
      (M = Fe, Ru) catalyze the [3+2] dipolar cycloaddition reaction between reactive
      nitrones and alpha,beta-unsaturated aldehydes to give chiral isoxazolidines with
      ee values of 75 to >96%. The stereochemistry of the major enantiomer is
      consistent with an endo approach of the nitrone to the Calpha-Si-face of the enal
      in the s-trans conformation in the (R,R)-catalyst site. The absolute
      configuration is based on an X-ray structure determination.

PMID- 11982356
TI  - Isolation and identification of surface-bound acetone enolate on Ni(111).
AB  - A surface-bound acetone enolate species has been synthesized on Ni(111) between
      260 and 340 K by two different routes catalyzed by surface Ni and O atoms:
      deprotonation of acetone and deacetylation of acetylacetone. The reaction
      pathways and surface species have been identified using reflection absorption
      infrared spectroscopy (RAIRS) in combination with isotopic substitution and
      density functional theory (DFT) calculations. Acetone enolate exhibits
      characteristic vibrational absorption bands at 1260, 1353, and 1545 cm-1 arising
      from mixed modes that involve CC stretching, CH3 bending, and CO stretching. This
      work conclusively proves the existence of stable acetone enolate species on a
      metal single-crystal surface and provides its first detailed characterization.

PMID- 11982357
TI  - An unnatural amino acid that induces beta-sheet folding and interaction in
      peptides.
AB  - This paper introduces a unique amino acid that can readily be incorporated into
      peptides to make them fold into beta-sheetlike structures that dimerize through
      beta-sheet interactions. This new amino acid, Orn(i-PrCO-Hao), consists of an
      ornithine residue with the beta-strand-mimicking amino acid Hao [J. Am. Chem.
      Soc. 2000, 122, 7654-7661] attached to its side chain. When Orn(i-PrCO-Hao) is
      incorporated into a peptide, or appended to its N-terminus, the Hao group
      hydrogen bonds to the three subsequent residues to form a beta-sheetlike
      structure. The amino acid Orn(i-PrCO-Hao) is readily used in peptide synthesis as
      its Fmoc derivative, Fmoc-Orn(i-PrCO-Hao)-OH (3). Fmoc-Orn(i-PrCO-Hao)-OH behaves
      like a regular amino acid in peptide synthesis and was uneventfully incorporated
      into the peptide o-anisoyl-Val-Orn(i-PrCO-Hao)-Phe-Ile-Leu-NHMe (4) through
      standard automated Fmoc solid-phase peptide synthesis, with DIC and HOAt as the
      coupling agent for Fmoc-Orn(i-PrCO-Hao)-OH and o-anisic acid and HATU as the
      coupling agent for all other couplings. A second synthetic strategy was developed
      to facilitate the preparation of peptides with N-terminal Orn(i-PrCO-Hao)
      residues, which avoids the need for the preparation of Fmoc-Orn(i-PrCO-Hao)-OH.
      In this strategy, Boc-Orn(Fmoc)-OH is used as the penultimate amino acid in the
      peptide synthesis, and i-PrCO-Hao-OH (2) is used as the final amino acid. N
      Terminal Orn(i-PrCO-Hao) peptide H-Orn(i-PrCO-Hao)-Phe-Ile-Leu-NHMe.TFA (5) was
      prepared in a fashion similar to that for 4, using DIC and HOAt as the coupling
      agent for i-PrCO-Hao-OH and HATU as the coupling agent for all other couplings.
      1H NMR transverse-ROESY, coupling constant, and chemical shift studies establish
      that peptide 4 forms a dimeric beta-sheetlike structure in CDCl3 solution. The 1H
      NMR studies also suggest that the ornithine unit adopts a well-defined turn
      conformation. Analogous 1H NMR studies of peptide 5 indicate that this TFA salt
      folds but does not dimerize in CD3OD solution. Collectively, these synthetic and
      spectroscopic studies establish that the amino acid Orn(i-PrCO-Hao) induces beta
      sheet structure and interactions in peptides in suitable organic solvents. Unlike
      the Hao amino acid, which acts as a prosthetic to replace three residues of the
      peptide strand, the Orn(i-PrCO-Hao) amino acid acts as a splint that helps
      enforce a beta-sheetlike structure without replacing the residues and their side
      chains. This feature of Orn(i-PrCO-Hao) is important, because it allows the
      creation of beta-sheet structure with minimal perturbation of the peptide
      sequence.

PMID- 11982358
TI  - Dissolution of cellulose [correction of cellose] with ionic liquids.
AB  - We report here initial results that demonstrate that cellulose can be dissolved
      without activation or pretreatment in, and regenerated from, 1-butyl-3
      methylimidazolium chloride and other hydrophilic ionic liquids. This may enable
      the application of ionic liquids as alternatives to environmentally undesirable
      solvents currently used for dissolution of this important bioresource.

PMID- 11982359
TI  - Molecular dynamics study of peptides in implicit water: ab initio folding of beta
      hairpin, beta-sheet, and beta beta alpha-motif.
AB  - In this communication, we have demonstrated that molecular dynamics simulations
      using a GB implicit solvation model with the all-atom based force field
      (CHARMM19) can describe the spontaneous folding of small peptides in aqueous
      solution. The native structures of peptides with various structural motifs (beta
      hairpin, beta-sheet, and betabetaalpha-moiety) were successfully predicted within
      reasonable time scales by MD simulations at moderately elevated temperatures. It
      is expected that the present simulations provide further insight into
      mechanism/pathways of the peptide folding.

PMID- 11982360
TI  - A potent polymer/pyridoxamine enzyme mimic.
AB  - An enzyme mimic consisting of pyridoxamines covalently linked to
      polyethyleneimine carrying long-chain alkyl groups converts pyruvic acid to dl
      alanine with as much as an 8000-fold acceleration relative to the reaction with
      simple pyridoxamine at the same pyridoxamine concentration. The acceleration by
      polymer is a strong function of the length of the alkyl chains that are appended.
      The polymer furnishes acid and base groups to catalyze the proton transfers that
      are involved in transamination.

PMID- 11982361
TI  - The effect of backbone cyclization on the thermodynamics of beta-sheet unfolding:
      stability optimization of the PIN WW domain.
AB  - Backbone cyclization is often used in attempts to enhance protein stability, but
      is not always successful as it is possible to remove stabilizing or introduce
      destabilizing interactions in the process. Cyclization of the PIN1 WW domain, a
      34-residue three-stranded beta-sheet structure, removes a favorable electrostatic
      interaction between its termini. Nevertheless, optimization of the linker
      connecting the N- and C-termini using information based on the previously
      determined ensemble of NMR structures leads to beta-sheets that are more stable
      than those derived from the linear sequence. Linkers that are too short or too
      long introduce strain, likely disrupting native interactions, leading to cyclic
      folds that are less stable than that of the linear sequence.

PMID- 11982362
TI  - Design and construction of an open multistranded beta-sheet polypeptide
      stabilized by a disulfide bridge.
AB  - The design and characterization of an open eight-stranded beta-sheet in a
      synthetic, 2-fold symmetric 70-residue peptide is described. The design strategy
      involves the generation of a 35-residue four-stranded beta-sheet peptide in which
      successive hairpins are nucleated by appropriately positioned (D)Pro-Xxx
      sequences. Oxidative dimerization using a single Cys residue positioned at the
      center of the C-terminal strand results in a disulfide-bridged eight-stranded
      structure. Nuclear Overhauser effects firmly establish an eight-stranded beta
      sheet in methanol. In water, the outer strands are frayed, but a well-defined
      four-stranded beta-sheet stabilized by a disulfide bridge and a hydrophobic
      cluster is determined from NMR data. Comparison of the precursor peptide with the
      disulfide-bridged dimer reveals considerable enhancement of beta-sheet content in
      the latter, suggesting that the disulfide cross-link is an effective strategy for
      the stabilization of beta-sheets.

PMID- 11982363
TI  - Development of a novel method to populate native disulfide-bonded intermediates
      for structural characterization of proteins: implications for the mechanism of
      oxidative folding of RNase A.
AB  - RNase A, a model protein for oxidative folding studies, has four native disulfide
      bonds. The roles of des [40-95] and des [65-72], the two native-like structured
      three-disulfide-bonded intermediates populated between 8 and 25 degrees C during
      the oxidative folding of RNase A, are well characterized. Recent work focuses on
      both the formation of these structured disulfide intermediates from their
      unstructured precursors and on the subsequent oxidation of the structured species
      to form the native protein. The major obstacles in this work are the very low
      concentration of the precursor species and the difficulty of isolating some of
      the structured intermediates. Here, we demonstrate a novel method that enables
      the native disulfide-bonded intermediates to be populated and studied regardless
      of whether they have stable structure and/or are present at low concentrations
      during the oxidative folding or reductive unfolding process. The application of
      this method enabled us to populate and, in turn, study the key intermediates with
      two native disulfide bonds on the oxidative folding pathway of RNase A; it also
      facilitated the isolation of des [58-110] and des [26-84], the other two native
      like structured des species whose isolation had thus far not been possible.

PMID- 11982364
TI  - Chromophore formation in resorcinarene solutions and the visual detection of mono
      and oligosaccharides.
AB  - The colorimetric properties of resorcinarene solutions had not been investigated
      since Baeyer's initial synthesis. We recently reported that solutions containing
      resorcinarene macrocycles develop color upon heating or standing. In the presence
      of saccharides, these solutions exhibit significant color changes which are
      easily seen. We herein present strong evidence that the solution color is due to
      macrocycle ring opening and oxidation. The optical responses to saccharides are
      due to complexation of the sugar with the acyclic chromophores. We apply these
      mechanistic insights toward the challenging problem of the visual detection of
      neutral oligosaccharides by simple chromogens. In addition, we also report the
      first single-crystal X-ray crystal structure determination of a rarely observed
      "diamond" resorcinarene stereoisomer.

PMID- 11982365
TI  - Theoretical evaluation of pK(a) in phosphoranes: implications for phosphate ester
      hydrolysis.
AB  - Knowledge of the pK(a) of phosphoranes is important for the interpretation of
      phosphate ester hydrolysis. Calculated pK(a)'s of the model phosphorane, ethylene
      phosphorane, are reported. The method of calculation is based on the use of
      dimethyl phosphate as a reference state for evaluating relative pK(a) values, and
      on the optimization of the oxygen and acidic hydrogen van der Waals radii to give
      reasonable pK(1)(a), pK(2)(a), and pK(3)(a) for phosphoric acid in solution.
      Density functional theory is employed to calculate the gas-phase protonation
      energies, and continuum dielectric methods are used to determine the solvation
      corrections. The calculated pK(1)(a) and p(2)(a) for the model phosphorane are
      7.9 and 14.3, respectively. These values are within the range of proposed
      experimental values, 6.5-11.0 for pK(1)(a), and 11.3-15.0 for pK(2)(a). The
      mechanistic implications of the calculated pK(a)'s are discussed.

PMID- 11982366
TI  - Radial control of recognition and redox processes with multivalent nanoparticle
      hosts.
AB  - Mixed Monolayer Protected Gold Clusters (MMPCs) featuring both hydrogen bonding
      and aromatic stacking molecular recognition functionalities have been used to
      create multivalent hosts for flavins. Multitopic binding of these hosts to flavin
      was shown to have a strong radial dependence: when the recognition site was
      brought closer to the MMPC surface, recognition was enhanced approximately 3-fold
      due to increased preorganization. The effect of preorganization is reversed upon
      reduction of flavin, where the MMPC with longer side chains bind the flavin guest
      approximately 7-fold stronger than the short chain counterpart due to unfavorable
      dipolar interactions between the electron-rich aromatic stacking units of the
      host and the anionic flavin guest. This fine-tuning of recognition and redox
      processes provides both a model for enzymatic systems and a tool for the
      fabrication of devices.

PMID- 11982367
TI  - Mechanistic dichotomy in CpRu(CH(3)CN)(3)PF(6) catalyzed enyne
      cycloisomerizations.
AB  - Enynes are easily accessible building blocks as a result of the rich chemistry of
      alkynes and thus represent attractive substrates for ring formation. A ruthenium
      catalyst for cycloisomerization effects such reaction of 1,6- and 1,7-enynes
      typically at room temperature in acetone or DMF under neutral conditions. The
      reaction is effective for forming five- and six-membered rings of widely
      divergent structure. The alkyne may bear both election-donating and election
      withdrawing substituents. The alkene may be di- or trisubstituted. Introduction
      of a quaternary center at the propargylic position of an ynoate, however,
      completely changes the nature of the reaction. In the case of a 1,6-enynoate, a
      seven-membered ring forms in excellent yield under equally mild conditions.
      Evidence is presented to indicate a complete change in mechanism. In the former
      case, the reaction involves the intermediacy of a ruthenacyclopentene. In the
      latter case, a C-H insertion to form a pi-allylruthenium intermediate is proposed
      and supported by deuterium-labeling studies. A rationale is presented for the
      structural dependence of the mechanism.

PMID- 11982368
TI  - Second generation light-driven molecular motors. Unidirectional rotation
      controlled by a single stereogenic center with near-perfect photoequilibria and
      acceleration of the speed of rotation by structural modification.
AB  - Nine new molecular motors, consisting of a 2,3-dihydro-2-methylnaphtho[2,1
      b]thiopyran or 2,3-dihydro-3-methylphenanthrene upper part and a (thio)xanthene,
      10,10-dimethylanthracene, or dibenzocycloheptene lower part, connected by a
      central double bond, were synthesized. A single stereogenic center, bearing a
      methyl substituent, is present in each of the motors. MOPAC93-AM1 calculations,
      NMR studies, and X-ray analysis revealed that these compounds have stable isomers
      with pseudoaxial orientation of the methyl substituent and less-stable isomers
      with pseudoequatorial orientation of the methyl substituent. The photochemical
      and thermal isomerization processes of the motors were studied by NMR and CD
      spectroscopy. The new molecular motors all show two cis-trans isomerizations upon
      irradiation, each followed by a thermal helix inversion, resulting in a 360
      degrees rotation around the central double bond of the upper part with respect to
      the lower part. The direction of rotation is controlled by a single stereogenic
      center created by the methyl substituent at the upper part. The speed of
      rotation, governed by the two thermal steps, was adjusted to a great extent by
      structural modifications, with half-lives for the thermal isomerization steps
      ranging from t(1/2)(theta) 233-0.67 h. The photochemical conversions of two new
      motors proceeded with near-perfect photoequilibria of 1:99.

PMID- 11982369
TI  - Catalytic cycle of rhodium-catalyzed asymmetric 1,4-addition of organoboronic
      acids. Arylrhodium, oxa-pi-allylrhodium, and hydroxorhodium intermediates.
AB  - The catalytic cycle of asymmetric 1,4-addition of phenylboronic acid to an
      alpha,beta-unsaturated ketone catalyzed by a rhodium-binap complex was
      established by use of RhPh(PPh(3))(binap) as a key intermediate. The reaction
      proceeds through three intermediates, phenylrhodium, oxa-pi-allylrhodium, and
      hydroxorhodium complexes, all of which were observed in NMR spectroscopic
      studies. The transformations between the three intermediates, that is, insertion,
      hydrolysis, and transmetalation, were also observed. On the basis of the
      catalytic cycle, a more active chiral catalyst, [Rh(OH)(binap)](2), was found and
      used successfully for the asymmetric 1,4-addition reactions.

PMID- 11982370
TI  - Selective preparation of pyridines, pyridones, and iminopyridines from two
      different alkynes via azazirconacycles.
AB  - Selective preparation of pyridine derivatives from two different alkynes and a
      nitrile was achieved by a novel procedure in which an alkyne and a nitrile couple
      first to give an azazirconacyclopentadiene followed by reaction with the second
      alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2). This procedure gives
      only single products of pyridine derivatives from two different symmetrical
      alkynes and a nitrile. Our novel procedure can be used even with two similar
      alkyl-substituted alkynes such as 3-hexyne and 4-octyne. Two possible pyridine
      isomers from 3-hexyne, 4-octyne, and acetonitrile could be completely and
      independently prepared as single products by this method. The origin of the
      selectivity comes from the addition order of two different alkynes. This method
      was applied for the formation of pyridones and iminopyridines using isocyanate
      and carbodiimide derivatives instead of nitriles, respectively. Reaction of an
      alkyne with Cp(2)ZrEt(2) and an isocyanate or a carbodiimide gives an
      azazirconacycle. Treatment of the azazirconacycle with the second alkyne in the
      presence of 1 equiv of NiCl(2)(PPh(3))(2) gave a pyridone or an iminopyridine
      derivative. The use of two different unsymmetrical alkynes afforded the pyridine
      with five different substituents when the first alkyne has a trialkylsilyl group
      and the second alkyne has a phenyl group as functional groups. On the other hand,
      azazirconacyclopentadienes reacted with propargyl bromide in the presence of CuCl
      with excellent regioselectivity to give tetrasubstituted pyridine derivatives as
      single products. With the assistance of the trialkylsilyl groups, pyridines with
      all different substituents including H were also prepared.

PMID- 11982371
TI  - cis-Stilbene and (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)benzene
      as mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: influence of
      the oxygen source and the counterion on the diastereoselectivity of the
      competitive concerted and radical-type oxygen transfer.
AB  - cis-Stilbene (1) has been epoxidized by a set of diverse oxygen donors [OxD],
      catalyzed by the Mn(III)(salen)X complexes 3 (X = Cl, PF(6)), to afford a mixture
      of cis- and trans-epoxides 2. The cis/trans ratios range from 29:71 (extensive
      isomerization) to 92:8, which depends both on the oxygen source [OxD] and on the
      counterion X of the catalyst. When (1 alpha,2 beta,3 alpha)-(2-ethenyl-3
      methoxycyclopropyl)-benzene (4) is used as substrate, a mechanistic probe which
      differentiates between radical and cationic intermediates, no cationic ring
      opening products are found in this epoxidation reaction; thus, isomerized epoxide
      product arises from intermediary radicals. The dependence of the
      diastereoselectivity on the oxygen source is rationalized in terms of a
      bifurcation step in the catalytic cycle, in which concerted Lewis-acid-activated
      oxygen transfer competes with stepwise epoxidation by the established Mn(V)(oxo)
      species. The experimental counterion effect is attributed to the computationally
      assessed ligand-dependent reaction profiles and stereoselectivities of the
      singlet, triplet, and quintet spin states available to the manganese species.

PMID- 11982372
TI  - Duplex oligomers defined via covalent casting of a one-dimensional hydrogen
      bonding motif.
AB  - Hydrogen-bonded tapes comprised of monomeric molecular precursors are used to
      define structural parameters for the design of related oligomers encoded with
      predetermined modes of assembly. Application of this "covalent casting" strategy
      vis-a-vis the one-dimensional H-bonding motif expressed by 2-amino-4,6
      dichlorotriazine has enabled the design of high-affinity duplex molecular
      strands. Dimeric, trimeric, and tetrameric duplex oligomers are prepared through
      an iterative synthetic protocol involving sequential homologation of the
      oligo(aminotriazine). The mode of assembly and interstrand affinity of homologous
      oligomers are established in solution by (1)H NMR dilution experiments,
      isothermal titration calorimetry (ITC), vapor pressure osmometry (VPO), cross
      hybridization experiments involving the analysis of dye-labeled strands via thin
      layer chromatography (TLC), and in the solid state by X-ray crystallographic
      analysis. Binding free energy per unimer (-Delta G degrees/n) increases
      significantly upon extension from monomer to dimer to trimer, signifying a strong
      positive cooperative effect. Nanomolar binding affinity (K(d) = 1.44 +/- 0.50 nM)
      was determined for the duplex trimer by ITC in 1,2-dichloroethane at 20 degrees
      C. In-register duplex formation is not observed for the tetramer, which appears
      to adopt an alternative binding mode. These data give insight into the structural
      and interactional features of the oligomers required for high-affinity, high
      specificity binding and define a platform for the design of second-generation
      systems and related duplex strands for use in nanoscale assembly.

PMID- 11982373
TI  - Synthesis, crystal structure, and H/D exchange of the inside protonated form of
      the cage imine 4,8,12-triaza-1-azoniatricyclo[6.6.3.2(4,12)]nonadec-1(15)-ene. A
      model for proton transfer through an aliphatic membrane.
AB  - The reaction of the inside protonated form of the tricyclic amine 1,4,8,12
      tetraazatricyclo[6.6.3.2(4,12)]nonadecane (1) with iron(III) affords the inside
      monoprotonated form of the corresponding imine 4,8,12-triaza-1
      azoniatricyclo[6.6.3.2(4,12)]nonadec-1(15)-ene (2), which was isolated as the
      tetrabromozincate salt (2a) in a yield of 78%. The crystal structure of 2a has
      been solved by X-ray diffraction at T = 120 K. In the imine cation the acidic
      hydrogen atom and the lone pairs of the nitrogen atoms are oriented toward the
      inside of the cavity. The acidic hydrogen atom is bound to a nitrogen atom
      belonging to the triazacyclononane entity. The imine double bond is situated
      between the N-atom of the triazacyclononane entity and the C-atom belonging to
      one of the three trimethylene bridges. The imine 2 is stable in acidic solution
      and the inside coordinated proton is very robust in acidic solution. In basic
      solution the imine reacts fast to give a quantitative formation of the inside
      protonated form of the hemiaminal 1,4,8,12
      tetraazatricyclo[6.6.3.2(4,12)]nonadecan-5-ol (3). The equilibrium constant K(im)
      = [3][H(+)]/[2] was determined at three different temperatures from
      potentiometric measurements, which gave K(im) = 1.57(1) x 10(-5) M at 25 degrees
      C, Delta S degrees = -83(1) J mol(-1) K(-)(1),and Delta H degrees = 2.6(3) kJ
      mol(-1) at I = 1.0 M (NaCl). The inside coordinated proton in 3 is labile in
      basic solution and the rate for NH/ND exchange was determined by (1)H NMR at
      three different temperatures. The reaction followed the expression k(obs) =
      k(ex)[OD(-)] with k(ex) = 0.0978(30) dm(3) mol(-1) s(-1) at 25 degrees C, Delta
      S(++) = 87(4) J mol(-1) K(-1), and Delta H(++) = 104.9(11) kJ mol(-1) at I = 1.0
      M (NaCl). The exchange rate is more than 5 x 10(6) times faster than that of the
      parent saturated cage 1. This extreme enhancement of reactivity is explained by
      an intramolecular proton transfer reaction mediated by hydroxy and oxy groups
      flipping in and out of the cavity, which mechanistically has resemblance to the
      transport of ions in a biological system.

PMID- 11982374
TI  - Structural Investigations into the retro-Diels-Alder Reaction. Experimental and
      Theoretical Studies.
AB  - The manifestations of the retro-Diels Alder reaction in the ground-state
      structures of a range of cyclopentadiene and cyclohexadiene cycloadducts 9-15
      have been investigated by a combination of techniques. These include low
      temperature X-ray crystallography, density functional calculations (B3LYP/6
      31G(d,p)) on both the ground states and transition states, and the measurement of
      (13)C-(13)C coupling constants. We have found that the carbon-carbon bonds
      (labeled bonds a and b), which break in the rDA, are longer in the cycloadducts 9
      15 than in their corresponding saturated analogues 9s-15s, which cannot undergo
      the rDA reaction. The degree of carbon-carbon bond lengthening appears to be
      related to the reactivity of the cycloadduct, thus the more reactive benzoquinone
      cycloadducts 5b and 13 have longer carbon-carbon bonds. Those cycloadducts 14 and
      15 which are predicted to undergo asynchronous reactions show differing degrees
      of carbon-carbon bond lengthening, reflecting the differing degrees of bond
      breaking at the calculated transition states for the rDA.

PMID- 11982375
TI  - Synthesis and investigation of [Cp(PMe(3))Rh(H)(H(2))](+) and its partially
      deuterated and tritiated isotopomers: evidence for a hydride/dihydrogen
      structure.
AB  - Hydrogenolysis of [Cp(PMe(3))Rh(Me)(CH(2)Cl(2))](+)BAr'(4)(-) (4, Ar' = 3,5
      C(6)H(3)(CF(3))(2)) in dichloromethane afforded the nonclassical polyhydride
      complex [Cp*PMe(3))Rh(H)(H(2))](+)BAr'(4)(-) (1), which exhibits a single hydride
      resonance at all accessible temperatures in the (1)H NMR spectrum. Exposure of
      solutions of 1 to D(2) or T(2) gas resulted in partial isotopic substitution in
      the hydride sites. Formulation of 1 as a hydride/dihydrogen complex was based
      upon T(1) (T(1)(min) = 23 ms at 150 K, 500 MHz), J(H-D) (ca. 10 Hz), and J(H-T)
      (ca. 70 Hz) measurements. The barrier (Delta G(++)) to exchange of hydride with
      dihydrogen sites was determined to be less than ca. 5 kcal/mol. Protonation of
      Cp(PMe(3))Rh(H)(2) (2) using H(OEt(2))(2)BAr'(4) resulted in binuclear species
      [(Cp(PMe(3))Rh(H))(2)(mu-H)](+)BAr'(4)(-) (3), which is formed in a reaction
      involving 1 as an intermediate. Complex 3 contains two terminal hydrides and one
      bridging hydride ligand which exchange with a barrier of 9.1 kcal/mol as observed
      by (1)H NMR spectroscopy. Additionally, the structures of 3 and 4, determined by
      X-ray diffraction, are reported.

PMID- 11982376
TI  - Intermolecular interactions in (arene)chromium carbonyl compounds: prediction of
      chiral crystal packing from racemate structure.
AB  - Six X-ray crystal structures are reported, all containing substituted
      triphenylmethanol derivative 4 either alone or as its mono or bis(chromium
      tricarbonyl) complexes. All four chromium complexes studied crystallize with two
      independent molecules in the crystallographic asymmetric unit. It is demonstrated
      that from the X-ray crystal structure of the acentric racemic (+/-)-(1pR,1'
      'R)(1pS,1' 'S)-[Cr(CO)(3)(eta(6)-t-BuC(6)H(3)(CMeOMe)CPh(2)OH)], (+/-)-3, it is
      possible to deduce the 4-fold helical structure of the chiral (-)-(1pR,1' 'R)
      isomer, (-)-3. The bimetallic derivatives demonstrate the ability to control
      intermolecular interactions by the positioning of relative stereochemistry.

PMID- 11982377
TI  - NMR and DFT analysis of [Re(2)H(2)(CO)(9)]: evidence of an eta(2)-H(2)
      intermediate in a new type of fast mutual exchange between terminal and bridging
      hydrides.
AB  - Protonation of the anion [Re(2)H(CO)(9)](-) (1) with a strong acid at 193 K
      affords the neutral complex [Re(2)H(2)(CO)(9)] (2), that in THF above 253 K
      irreversibly loses H(2) to give [Re(2)(CO)(9)(THF)], previously obtained by room
      temperature protonation of 1. Treatment of 2 with NEt(4)OH restores the starting
      anion 1. Variable temperature (1)H and (13)C NMR spectra as well as T(1)
      measurements agree with the formulation of 2 as a classical [Re(2)H(mu-H)(CO)(9)]
      complex, in which two dynamic processes takes place. The "windshield-wiper
      motion" observed in several related complexes equalizes the two carbonyls trans
      to the hydrides (E(a) = 44(1) kJ mol(-)(1)), while another much faster process
      equalizes bridging and terminal hydrides already at 172 K. The variable
      temperature behavior of the (1)H transverse relaxation times revealed also proton
      exchange between 2, water, and the parent anion 1 (due to the acidity of 2), but
      such a process is too slow to account for the fast hydrides exchange in 2. The
      nature of the latter process has been investigated both experimentally and
      theoretically. Kinetic data, obtained by the analysis of the variable temperature
      (1)H spectra (E(a) = 24.5(5) kJ mol(-1)), revealed a small normal kinetic isotope
      effect (ca. 1.5). The (2)H chemical shift of the fully deuterated isotopomer 2
      d(2) was found isochronous with 2, thus ruling out the presence of a significant
      concentration of a nonclassical [Re(2)(eta(2)-H(2))(CO)(9)] tautomer, in fast
      exchange with the classical dihydride. Density functional theory (DFT)
      calculations, carried out at the B3LYP level, confirmed the formulation of
      [Re(2)H(2)(CO)(9)] as a classical complex. However, when DFT was used to obtain a
      detailed description of the dynamic behavior of 2 in solution, a new type of
      hydride fast exchange emerged, involving the nonclassical tautomer as a
      relatively high energy (12.7 kJ mol(-1)) intermediate. Isotopic perturbation of
      the equilibrium by partial deuteration of 2 indicated the preference of deuterium
      for the bridging sites, with Delta H degrees = -475(4) J mol(-1) and Delta S
      degrees = -0.80(2) J K(-1) mol(-1). The same preference was observed in the anion
      [Re(2)H(mu-H)Cl(CO)(8)](-).

PMID- 11982378
TI  - Bifunctional pincer-type organometallics as substrates for organic
      transformations and as novel building blocks for polymetallic materials.
AB  - The reactivity of the bifunctionalized ligand NC(Br)N-I 1
      [IC(6)H(2)(CH(2)NMe(2))(2)-3,5-Br-4] has been studied as a versatile synthon for
      organic and/or organometallic synthesis. Chemoselective metalation (M = Pd, Pt,
      Li) at the C(aryl)-I or C(aryl)-Br bonds was achieved by choosing the appropriate
      metal precursors. In this way a series of Pt(II) and Pd(II) complexes were
      prepared that have a second functional group available for further reactions.
      These Pt(II) and Pd(II) complexes were subjected to a wide range of organic and
      organometallic reactions, revealing the remarkable stability of their M-C sigma
      bond and opening an easy route for the synthesis of mono- and (hetero)bimetallic
      building blocks. The scope of the chemistry of such building blocks shows that
      they are good candidates for use in the synthesis of dendrimers,
      bioorganometallic systems, or polymetallic materials. The X-ray crystal
      structures of the most representative complexes (2, 3a, 19, 20, and 24) are also
      reported.

PMID- 11982379
TI  - Mixed-metal cluster chemistry. 19. Crystallographic, spectroscopic,
      electrochemical, spectroelectrochemical, and theoretical studies of
      systematically varied tetrahedral group 6-iridium clusters.
AB  - A systematically varied series of tetrahedral clusters involving ligand and core
      metal variation has been examined using crystallography, Raman spectroscopy,
      cyclic voltammetry, UV-vis-NIR and IR spectroelectrochemistry, and approximate
      density functional theory, to assess cluster rearrangement to accommodate steric
      crowding, the utility of metal-metal stretching vibrations in mixed-metal cluster
      characterization, and the possibility of tuning cluster electronic structure by
      systematic modification of composition, and to identify cluster species resultant
      upon electrochemical oxidation or reduction. The 60-electron tetrahedral clusters
      MIr(3)(CO)(11-x)(PMe(3))(x)(eta(5)-Cp) [M = Mo, x = 0, Cp = C(5)H(4)Me (5),
      C(5)HMe(4) (6), C(5)Me(5) (7); M = W, Cp = C(5)H(4)Me, x = 1 (13), x = 2 (14)]
      and M(2)Ir(2)(CO)(10-x)(PMe(3))(x)(eta(5)-Cp) [M = Mo, x = 0, Cp = C(5)H(4)Me
      (8), C(5)HMe(4) (9), C(5)Me(5) (10); M = W, Cp = C(5)H(4)Me, x = 1 (15), x = 2
      (16)] have been prepared. Structural studies of 7, 10, and 13 have been
      undertaken; these clusters are among the most sterically encumbered, compensating
      by core bond lengthening and unsymmetrical carbonyl dispositions (semi-bridging,
      semi-face-capping). Raman spectra for 5, 8, WIr(3)(CO)(11)(eta(5)-C(5)H(4)Me)
      (11), and W(2)Ir(2)(CO)(10)(eta(5)-C(5)H(4)Me)(2) (12), together with the
      spectrum of Ir(4)(CO)(12), have been obtained, the first Raman spectra for mixed
      metal clusters. Minimal mode-mixing permits correlation between A(1) frequencies
      and cluster core bond strength, frequencies for the A(1) breathing mode
      decreasing on progressive group 6 metal incorporation, and consistent with the
      trend in metal-metal distances [Ir-Ir < M-Ir < M-M]. Cyclic voltammetric scans
      for 5-15, MoIr(3)(CO)(11)(eta(5)-C(5)H(5)) (1), and Mo(2)Ir(2)(CO)(10)(eta(5)
      C(5)H(5))(2) (3) have been collected. The [MIr(3)] clusters show irreversible one
      electron reduction at potentials which become negative on cyclopentadienyl alkyl
      introduction, replacement of molybdenum by tungsten, and replacement of carbonyl
      by phosphine. These clusters show two irreversible one-electron oxidation
      processes, the easier of which tracks with the above structural modifications; a
      third irreversible oxidation process is accessible for the bis-phosphine cluster
      14. The [M(2)Ir(2)] clusters show irreversible two-electron reduction processes;
      the tungsten-containing clusters and phosphine-containing clusters are again more
      difficult to reduce than their molybdenum-containing or carbonyl-containing
      analogues. These clusters show two one-electron oxidation processes, the easier
      of which is reversible/quasi-reversible, and the more difficult of which is
      irreversible; the former occur at potentials which increase on cyclopentadienyl
      alkyl removal, replacement of tungsten by molybdenum, and replacement of
      phosphine by carbonyl. The reversible one-electron oxidation of 12 has been
      probed by UV-vis-NIR and IR spectroelectrochemistry. The former reveals that
      12(+) has a low-energy band at 8000 cm(-1), a spectrally transparent region for
      12, and the latter reveals that 12(+) exists in solution with an all-terminal
      carbonyl geometry, in contrast to 12 for which an isomer with bridging carbonyls
      is apparent in solution. Approximate density functional calculations (including
      ZORA scalar relativistic corrections) have been undertaken on the various charge
      states of W(2)Ir(2)(CO)(10)(eta(5)-C(5)H(5))(2) (4). The calculations suggest
      that two-electron reduction is accompanied by W-W cleavage, whereas one-electron
      oxidation proceeds with retention of the tetrahedral core geometry. The
      calculations also suggest that the low-energy NIR band of 12(+) arises from a
      sigma(W-W) --> sigma*(W-W) transition.

PMID- 11982380
TI  - Use of the pseudophase model in the interpretation of reactivity under restricted
      geometry conditions. An application to the study of the [Ru(NH(3))(5)pz](2+) +
      S(2)O(8)(2-) electron-transfer reaction in different microheterogeneous systems.
AB  - The title reaction has been studied under restricted geometry conditions,
      comprising aqueous solutions of a polymer (DNA), cyclodextrins, and dendrimers as
      well as (CTA)Cl micellar solutions and sodium bis(2-ethylhexyl)sulfosuccinate
      (AOT)/water/oil microemulsions. The results are interpreted by taking as a
      general basis the pseudophase model, modified in some cases in order to take into
      account the specificity of the reaction medium. These modifications describe the
      anti-cooperative character of the binding of the substrates to the surfaces and
      the changes of the electric potential at the surfaces. The conclusion is that the
      pseudophase model is a powerful tool for the interpretation of kinetic data in
      the reaction media considered in this work, provided that the specificity of
      these media were incorporated into the model.

PMID- 11982381
TI  - Stepwise charge separation and charge recombination in ferrocene-meso,meso-linked
      porphyrin dimer-fullerene triad.
AB  - A meso,meso-linked porphyrin dimer [(ZnP)(2)] as a light-harvesting chromophore
      has been incorporated into a photosynthetic multistep electron-transfer model for
      the first time, including ferrocene (Fc), as an electron donor and fullerene
      (C(60)) as an electron acceptor to construct the ferrocene-meso,meso-linked
      porphyrin dimer-fullerene system (Fc-(ZnP)(2)-C(60)). Photoirradiation of Fc
      (ZnP)(2)-C(60) results in photoinduced electron transfer from the singlet excited
      state of the porphyrin dimer [(1)(ZnP)(2)] to the C(60) moiety to produce the
      porphyrin dimer radical cation-C(60) radical anion pair, Fc-(ZnP)(2)(*+)-C(60)(*
      ). In competition with the back electron transfer from C(60)(*-) to (ZnP)(2)(*+)
      to the ground state, an electron transfer from Fc to (ZnP)(2)(*+) occurs to give
      the final charge-separated (CS) state, that is, Fc(+)-(ZnP)(2)-C(60)(*-), which
      is detected as the transient absorption spectra by the laser flash photolysis.
      The quantum yield of formation of the final CS state is determined as 0.80 in
      benzonitrile. The final CS state decays obeying first-order kinetics with a
      lifetime of 19 micros in benzonitrile at 295 K. The activation energy for the
      charge recombination (CR) process is determined as 0.15 eV in benzonitrile, which
      is much larger than the value expected from the direct CR process to the ground
      state. This value is rather comparable to the energy difference between the
      initial CS state (Fc-(ZnP)(2)(*+)-C(60)(*-)) and the final CS state (Fc(+)
      (ZnP)(2)-C(60)(*-)). This indicates that the back electron transfer to the ground
      state occurs via the reversed stepwise processes,that is, a rate-limiting
      electron transfer from (ZnP)(2) to Fc(+) to give the initial CS state (Fc
      (ZnP)(2)(*+)-C(60)(*-)), followed by a fast electron transfer from C(60)(*-) to
      (ZnP)(2)(*+) to regenerate the ground state, Fc-(ZnP)(2)-C(60). This is in sharp
      contrast with the extremely slow direct CR process of bacteriochlorophyll dimer
      radical cation-quinone radical anion pair in bacterial reaction centers.

PMID- 11982382
TI  - A density functional theory study on the active center of Fe-only hydrogenase:
      characterization and electronic structure of the redox states.
AB  - We have carried out extensive density functional theory (DFT) calculations for
      possible redox states of the active center in Fe-only hydrogenases. The active
      center is modeled by [(H(CH(3))S)(CO)(CN(-))Fe(p)(mu-DTN)(mu-CO)Fe(d)(CO)(CN(
      ))(L)](z)() (z is the net charge in the complex; Fe(p)= the proximal Fe, Fe(d) =
      the distal Fe, DTN = (-SCH(2)NHCH(2)S-), L is the ligand that bonds with the
      Fe(d) at the trans position to the bridging CO). Structures of possible redox
      states are optimized, and CO stretching frequencies are calculated. By a detailed
      comparison of all the calculated structures and the vibrational frequencies with
      the available experimental data, we find that (i) the fully oxidized, inactive
      state is an Fe(II)-Fe(II) state with a hydroxyl (OH(-)) group bonded at the
      Fe(d), (ii) the oxidized, active state is an Fe(II)-Fe(I) complex which is
      consistent with the assignment of Cao and Hall (J. Am. Chem. Soc. 2001, 123,
      3734), and (iii) the fully reduced state is a mixture with the major component
      being a protonated Fe(I)-Fe(I) complex and the other component being its self
      arranged form, Fe(II)-Fe(II) hydride. Our calculations also show that the
      exogenous CO can strongly bond with the Fe(II)-Fe(I) species, but cannot bond
      with the Fe(I)-Fe(I) complex. This result is consistent with experiments that CO
      tends to inhibit the oxidized, active state, but not the fully reduced state. The
      electronic structures of all the redox states have been analyzed. It is found
      that a frontier orbital which is a mixing state between the e(g) of Fe and the 2
      pi of the bridging CO plays a key role concerning the reactivity of Fe-only
      hydrogenases: (i) it is unoccupied in the fully oxidized, inactive state, half
      occupied in the oxidized, active state, and fully occupied in the fully reduced
      state; (ii) the e(g)-2 pi orbital is a bonding state, and this is the key reason
      for stability of the low oxidation states, such as Fe(I)-Fe(I) complexes; and
      (iii) in the e(g)-2 pi orbital more charge accumulates between the bridging CO
      and the Fe(d) than between the bridging CO and the Fe(p), and the occupation
      increase in this orbital will enhance the bonding between the bridging CO and the
      Fe(d), leading to the bridging-CO shift toward the Fe(d).

PMID- 11982383
TI  - Synthesis, characterization, and spectroscopy of 4,7,12,15-[2.2]paracyclophane
      containing donor and acceptor groups: impact of substitution patterns on through
      space charge transfer.
AB  - This paper reports the synthesis of 4,7,12,15-tetra(4'
      dihexylaminostyryl)[2.2]paracyclophane (1), 4-(4'-dihexylaminostyryl)-7,12,15
      tri(4' '-nitrostyryl)[2.2]paracyclophane (2), 4,7-bis(4'-dihexylaminostyryl)
      12,15-bis(4' '-nitrostyryl)-[2.2]paracyclophane (3), 4,7,12-tris(4'
      dihexylaminostyryl)-15-(4' '-nitrostyryl)[2.2]paracyclophane (4), 4,15-bis(4'
      dihexylaminostyryl)-7,12-bis(4' '-nitrostyryl)[2.2]paracyclophane (5), and 4,12
      bis(4'-dihexylaminostyryl)-7,15-bis(4' '-nitrostyryl)[2.2]paracyclophane (6).
      These molecules represent different combinations of bringing together
      distyrylbenzene chromophores containing donor and acceptor groups across a
      [2.2]paracyclophane (pCp) bridge. X-ray diffraction studies show that the lattice
      arrangements of 1 and 3 are considerably different from those of the parent
      chromophores 1,4-bis(4'dihexylaminostyryl)benzene (DD) and 1,4-di(4'
      nitrostyryl)benzene (AA). Differences are brought about by the constraint by the
      pCp bridge and by virtue of chirality in the "paired" species. The absorption and
      emission spectra of 1-6 are also presented. Clear evidence of delocalization
      across the pCp structure is observed. Further, in the case of 2, 3, and 4,
      emission from the second excited state takes place.

PMID- 11982384
TI  - Exchange coupling of transition-metal ions through hydrogen bonding: a
      theoretical investigation.
AB  - Density functional calculations for full structures of dimers of Cu(II) complexes
      linked via O-H...O hydrogen bonds provide exchange-coupling constants that are in
      excellent agreement with experimentally reported values. Magneto-structural
      correlations between the exchange-coupling constant and the O...O distance or the
      separation between the coordination planes of the two monomers are analyzed. The
      calculations support the orbital models usually employed in qualitative
      interpretations of magneto-structural correlations, showing excellent
      correlations between the calculated coupling constants and the square of the
      orbital gap or of the overlap between the two magnetic orbitals. The orbital gap
      responsible for the antiferromagnetic coupling is seen to result from direct
      through-space overlap between the oxygen atoms of the two monomers, whereas the
      hydrogen bonds play an essentially structural role by holding these oxygen atoms
      in close proximity.

PMID- 11982385
TI  - Hydrogen bonding and the conformations of poly(alkyl acrylamides).
AB  - The conformations of poly(alkyl acrylamide) oligomers in nonpolar solvents were
      studied using molecular dynamics techniques. Poly(methyl acrylamide) was found to
      collapse to a globule-like conformation at low temperatures; however, excluded
      volume effects inhibited the collapse of poly(octadecyl acrylamide). A high
      density of structured units, characterized by a trans-gauche-trans-trans-gauche
      trans torsional sequence along the backbone, was noted in all simulations. Such
      units were found to create a particularly stable set of intramolecular hydrogen
      bonds. An oligomer constructed with these stable units was found to have
      significantly lower minimized energy than both the all-trans and the helical
      backbone conformations. The constructed conformation had lower Coulomb energy
      (more hydrogen bonds) than the all-trans conformation and lower dihedral energy
      (less backbone distortion) than the helical conformation. The propensity for
      poly(octadecyl acrylamide) to form hydrogen bonds introduced significant disorder
      into the orientation of the alkyl side chains. This disorder would inhibit
      crystallization and restrict the ability of such polymers to form epitaxial seeds
      for nucleating paraffin crystals.

PMID- 11982386
TI  - Conformation-dependent reaction thermochemistry: study of lactones and lactone
      enolates in the gas phase.
AB  - Gas-phase acidities (Delta H degrees (acid)) of lactones with ring sizes from
      four to seven have been measured on a Fourier transform ion cyclotron resonance
      mass spectrometer. Electron affinities (EAs) of the corresponding lactone enolate
      radicals were measured on a continuous-wave ion cyclotron resonance mass
      spectrometer, and the bond dissociation energies (BDEs) of the alpha C-H bonds
      were derived. In order of increasing ring size, Delta H degrees (acid) = 368.7 +/
      2., 369.4 +/- 2.2, 367.3 +/- 2.2, and 368.3 +/- 2.2 kcal/mol and BDE = 99.4 +/-
      2.3, 94.8 +/- 2.3, 89.2 +/- 2.3, and 92.8 +/- 2.4 kcal/mol for beta
      propiolactone, gamma-butyrolactone, delta-valerolactone, and epsilon
      caprolactone, respectively. For their corresponding enolate radicals, EA = 44.1
      +/- 0.3, 38.8 +/- 0.3, 35.3 +/- 0.3, and 37.9 +/- 0.6 kcal/mol. All of these
      lactones are considerably more acidic than methyl acetate, consistent with a
      dipole repulsion model. Both BDEs and EAs show a strong dependence on ring size,
      whereas Delta H degrees (acid) does not. These findings are discussed, taking
      into account differential electronic effects and differential strain between the
      reactant and product species in each reaction.

PMID- 11982387
TI  - Effects of thioamide substitutions on the conformation and stability of alpha-
      and 3(10)-helices.
AB  - Thiopeptides, formed by replacing the amide oxygen atom with a sp(2) sulfur atom,
      are useful in protein engineering and drug design because they confer resistance
      to enzymatic degradation and are predicted to be more rigid. This report
      describes our free molecular dynamics simulations with explicit water and free
      energy calculations on the effects of thio substitutions on the conformation of
      alpha-helices, 3(10)-helices, and their relative stability. The most prominent
      structural effect of thio substitution is the increase in the hydrogen bond
      distance from 2.1 A for normal peptides to 2.7 A for thiopeptides. To accommodate
      for the longer C[double bond]S...H-N hydrogen bond, the (phi, psi) dihedral
      angles of the alpha-helix changed from (-66 degrees, -42 degrees) to (-68
      degrees, -38 degrees), and the rise per turn increased from 5.5 to 6.3 A. For
      3(10)-helices, the (phi, psi) dihedral angles (-60 degrees, -20 degrees) and rise
      per turn (6.0 A) changed to (-66 degrees, -12 degrees) and 6.8 A, respectively.
      In terms of relative stability, the most prominent change upon thio substitution
      is the decrease in the free energy difference, Delta A(alpha --> 3(10)), from 14
      to 3.5 kcal/mol. Therefore, normal peptides are less likely to form 3(10)-helix
      than are thiopeptides. Component analysis of the Delta A(alpha --> 3(10)) reviews
      that the entropy advantage of the 3(10)-helix for both Ac-Ala(10)-NHMe and Act
      Alat(10)-NHMe is attributed to the 3(10)-helix being more flexible than the alpha
      helix. Interestingly, upon thio substitution, this differential flexibility is
      even more apparent because the alpha-helix conformation of Act-Alat(10)-NHMe
      becomes more rigid due to the bulkier sulfur atom.

PMID- 11982388
TI  - A density functional theory study clarifying the reactions of conjugated ketenes
      with formaldimine. A plethora of pericyclic and pseudopericyclic pathways.
AB  - The reactions of vinylketene (1a), imidoylketene (1b), and formylketene (1c) with
      formaldimine (2) were studied at the B3LYP/6-31G* level. For the cycloadditions
      of these conjugated ketenes with 2, several possible pathways to both [4 + 2] and
      [2 + 2] products were examined. The lowest energy [2 + 2] pathways are, in most
      cases, calculated to be stepwise, forming the products via rate-determining
      conrotatory electrocyclization of zwitterionic intermediates. However, concerted
      transition structures analogous to the ketene plus ethene [2 + 2] cycloaddition
      reaction were also located; the existence of multiple transition states offers a
      resolution to a long-standing controversy regarding the mechanism of ketene plus
      imine cycloadditions. Both stepwise and concerted [4 + 2] pathways were
      calculated for 2b and for 2c; both these pathways are pseudopericyclic. The
      inherently low barriers associated with pseudopericyclic transition states
      provide an explanation of the experimental preference for [4 + 2] cycloadditions
      of alpha-oxoketenes and predict [4 + 2] cycloadditions should also be favored for
      imidoylketenes. For a vinylketene constrained to a Z-geometry, the concerted [4 +
      2] cycloaddition is also predicted to be the lowest energy pathway. An
      explanation is offered for the unusual thermal equilibration from a six-membered
      ring (3d) to a four-membered ring (4d) observed by Sato et al. Transition
      structures for facile pseudopericyclic 1,3- and 1,5-hydrogen shifts in the
      zwitterions were also calculated.

PMID- 11982389
TI  - Activation of gold on titania: adsorption and reaction of SO(2) on
      Au/TiO(2)(110).
AB  - Synchrotron-based high-resolution photoemission and first-principles density
      functional slab calculations were used to study the interaction of gold with
      titania and the chemistry of SO(2) on Au/TiO(2)(110) surfaces. The deposition of
      Au nanoparticles on TiO(2)(110) produces a system with an extraordinary ability
      to adsorb and dissociate SO(2). In this respect, Au/TiO(2) is much more
      chemically active than metallic gold or stoichiometric titania. On Au(111) and
      rough polycrystalline surfaces of gold, SO(2) bonds weakly and desorbs intact at
      temperatures below 200 K. For the adsorption of SO(2) on TiO(2)(110) at 300 K,
      SO(4) is the only product (SO(2) + O(oxide) --> SO(4,ads)). In contrast,
      Au/TiO(2)(110) surfaces (theta;(Au) < or = 0.5 ML) fully dissociate the SO(2)
      molecule under identical reaction conditions. Interactions with titania
      electronically perturb gold, making it more chemically active. Furthermore, our
      experimental and theoretical results show quite clearly that not only gold is
      perturbed when gold and titania interact. The adsorbed gold, on its part,
      enhances the reactivity of titania by facilitating the migration of O vacancies
      from the bulk to the surface of the oxide. In general, the complex coupling of
      these phenomena must be taken into consideration when trying to explain the
      unusual chemical and catalytic activity of Au/TiO(2). In many situations, the
      oxide support can be much more than a simple spectator.

PMID- 11982390
TI  - Honey from plants containing pyrrolizidine alkaloids: a potential threat to
      health.
AB  - Following scientific risk assessments, several countries have imposed strict
      regulations on herbal medicines containing 1,2-dehydro-pyrrolizidine alkaloids.
      Using published data on the plants used in honey production, pyrrolizidine
      alkaloid-containing plants are shown in this review to represent a significant
      source of honey worldwide. This observation, honey consumption data, reported
      levels of pyrrolizidine alkaloids in honeys, and consideration of tolerable
      exposure levels determined for pyrrolizidine alkaloids in herbal medicines, leads
      to the conclusion that some honey is a potential threat to health, especially for
      infants and fetuses, and further investigation is warranted.

PMID- 11982391
TI  - Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in
      transgenic plants, antifungal activity, and metabolism.
AB  - Resistance of plants to infection by phytopathogenic microorganisms is the result
      of multiple defense reactions comprising both constitutive and inducible
      barriers. In grapevine, the most frequently observed and best characterized
      defense mechanisms are the accumulation of phytoalexins and the synthesis of PR
      proteins. Particular attention has been given here to stilbene phytoalexins
      produced by Vitaceae, specifically, their pathway of biosynthesis (including
      stilbene phytoalexin gene transfer experiments to other plants) and their
      biological activity together with fungal metabolism.

PMID- 11982392
TI  - Application of a monoclonal antibody-based enzyme-linked immunosorbent assay for
      the determination of ractopamine in incurred samples from food animals.
AB  - A monoclonal antibody-based ractopamine immunoassay has been applied to incurred
      samples from sheep and cattle. Results obtained by immunoassay were compared with
      those from high-performance liquid chromatography (HPLC). Three sets of sample
      extracts containing primarily unmetabolized ractopamine were analyzed.
      Correlation of HPLC with enzyme-linked immunosorbent assay (ELISA) for beef liver
      samples gave an r(2) = 0.98 despite rather low ractopamine concentrations (range
      1.1-13.4 ng/mL, n = 6). Ractopamine concentrations in cow urine samples treated
      by solid phase extraction, to remove ractopamine metabolites, also showed a high
      correlation between the HPLC and the ELISA results (r(2) = 0.95, range 1.0-275
      ng/mL, n = 61). In contrast, HPLC and ELISA analyses of ractopamine in sheep
      urine were not well-correlated (r(2) = 0.58, range 0.85-51 ng/mL, n = 34). When
      ractopamine conjugates in urine samples were hydrolyzed with hydrolytic enzymes,
      ELISA and HPLC methods were highly correlated [r(2) = 0.94 for sheep (range 123
      10 554 ppb, n = 60) and an r(2) = 0.98 for cattle (range 14-8159 ppb, n = 62)].
      Tissues contained only minute amounts of ractopamine, and after 7-day withdrawal
      periods, less than 1 ppb of free ractopamine was detected. Ractopamine was
      rapidly metabolized in both cattle and sheep. The difference in ractopamine
      concentration of urine samples before and after hydrolysis indicated that only 1
      5% of ractopamine was excreted unmetabolized. Results from this study indicate
      that the monoclonal antibody-based ELISA could be useful for a sensitive,
      quantitative, or qualitative ractopamine screening assay.

PMID- 11982393
TI  - Stable isotope labeling pattern of resveratrol and related natural stilbenes.
AB  - The stable isotope characterization of resveratrol 1 from Polygonum cuspidatum
      and of related natural stilbenes 11 and 12 obtained by hydrolysis of the
      corresponding glucosides 2 and 3 from Rheum is reported. The C(6)-C(2)-C(6)
      framework of suitably protected derivatives of 1, 2, and 3 has been degraded with
      ozone to the C(6)-C(1) aldehydes 4, 5, 9, and 10, retaining all hydrogen atoms of
      the precursors. The natural and synthetic derivatives are characterized and
      distinguished by natural abundance deuterium nuclear magnetic resonance studies.
      In the case of anisaldehyde 4 the two series show, as expected, the
      characteristic difference of the aromatic labeling. The formyl deuterium contents
      of 4 and 5 from resveratrol are remarkably different, seemingly reflecting the
      different enrichments existing between positions 3 and 2, respectively, of the
      phenylpropanoid precursor. The positional delta(18)O values of the extractive
      materials 1-3 were also determined. In this instance a selective deoxygenation
      procedure was adopted, leading from 1 to the products 6, 7, and 8. The delta(18)O
      values of the latter compounds reveal, respectively, those at position 4' and
      positions 3 and 5 of 1. Similarly, the phenolic products 11 and 12 were converted
      into 13 and 14. From the delta(18)O values of the single components it is
      possible to design a detailed map of the oxygen fractionations which
      characterizes the stilbenes 1-3. In particular, the oxygen present at position 4'
      of the phenylpropanoid moiety of 1-3 shows delta(18)O values of +11.5, +1.8, and
      +6.7 per thousand, respectively. Moreover, the phenolic oxygen atom at position
      3' of rhapontin 3 shows a value of +11.7 per thousand. The data are compared with
      those previously obtained on structurally related compounds. These results show
      the utility of simple chemical degradations in the stable isotope
      characterization of structurally complex food components.

PMID- 11982394
TI  - Supercritical fluid extraction and high-performance liquid chromatographic
      determination of phloroglucinols in St. John's Wort (Hypericum perforatum L.).
AB  - A small-scale supercritical fluid extraction (SFE) method was developed for the
      selective extraction of phloroglucinols from St. John's wort (SJW) leaf/flower
      mixtures using supercritical carbon dioxide (CO(2)). The extraction efficiency
      was investigated as influenced by pressure, temperature, time, and modifier. The
      optimized condition of SFE was carried out at 3.80 x 10(4) kpa (5500 psi) and 50
      degrees C. Samples were held in static extraction for 10 min, followed by a
      dynamic extraction for 90 min at the flow rate of 1 mL/min. A simple and
      sensitive HPLC method was developed for the analysis of hyperforin and
      adhyperforin, the major phloroglucinols, in the SFE extract of SJW.

PMID- 11982395
TI  - Postcolumn derivatization method for determination of reducing and phosphorylated
      sugars in chicken by high performance liquid chromatography.
AB  - A postcolumn derivatization method is described for determination of reducing
      sugars and phosphorylated reducing sugars from chicken meat and other foods using
      high-performance liquid chromatography (HPLC). Reducing sugars are extracted with
      ethanol/water, separated on a Kromasil amine-bonded column by isocratic analysis
      using acetonitrile/water as the mobile phase, and, after postcolumn reaction with
      tetrazolium blue, are determined by the resulting absorbance at 550 nm.
      Phosphorylated sugars are first dephosphorylated using alkaline phosphatase and
      then determined by the same method.

PMID- 11982396
TI  - Assessment of pro-oxidant activity of foods by kinetic analysis of crocin
      bleaching.
AB  - The pro-oxidant activity of potent oxidants and foods was determined using the
      kinetic analysis of crocin bleaching. In its reduced form, crocin has an
      absorption band at 443 nm, which disappears upon oxidation by a generic radical
      species. Hydroxyl radicals generated by hydrogen peroxide, peroxyl radicals from
      ABAP, and the stable free radical DPPH(*) were allowed to react with crocin in an
      aqueous solution at 40 degrees C. Pro-oxidant activity was taken as the ratio
      between the decrease in crocin absorbance at 5 min and the relevant oxidant
      concentration. The test proposed was used to evaluate the pro-oxidant activity of
      widely consumed foods such as pasteurized skim milk and bread. They both exerted
      significant pro-oxidant activities, which were attributed to the early
      nonenzymatic browning products formed upon heat treatment.

PMID- 11982397
TI  - Novel fluorometric assay for hydroxyl radical prevention capacity using
      fluorescein as the probe.
AB  - A novel fluorometric method has been developed to evaluate hydroxyl radical
      prevention capacity using fluorescein (FL) as the probe. The hydroxyl radical is
      generated by a Co(II)-mediated Fenton-like reaction, and the hydroxyl radical
      formation under the experimental condition is indirectly confirmed by the
      hydroxylation of p-hydroxybenzoic acid. The fluorescence decay curve of FL is
      monitored in the absence or presence of antioxidant, the area under the
      fluorescence decay curve (AUC) is integrated, and the net AUC, which is an index
      of the hydroxyl radical prevention capacity, is calculated by subtracting the AUC
      of the blank from that of the antioxidant. Gallic acid is chosen as a reference
      standard, and the activity of sample is expressed as gallic acid equivalents. The
      method is rigorously validated through linearity, precision, accuracy, and
      ruggedness. A wide range of phenolic antioxidants is analyzed, and the hydroxyl
      radical prevention capacity is mainly due to the metal-chelating capability of
      the compounds.

PMID- 11982398
TI  - Analysis of fumonisin B(1) in Fusarium proliferatum-infected asparagus spears and
      garlic bulbs from Germany by liquid chromatography-electrospray ionization mass
      spectrometry.
AB  - Fusarium proliferatum is one of a group of fungal species that produce fumonisins
      and is considered to be a pathogen of many economically important plants. The
      occurrence of fumonisin B(1) (FB(1)) in F. proliferatum-infected asparagus spears
      from Germany was investigated using a liquid chromatography-electrospray
      ionization mass spectrometry (LC-ESI-MS) method with isotopically labeled
      fumonisin FB(1)-d(6) as internal standard. FB(1) was detected in 9 of the 10
      samples in amounts ranging from 36.4 to 4513.7 ng/g (based on dry weight).
      Furthermore, the capability of producing FB(1) by the fungus in garlic bulbs was
      investigated. Therefore, garlic was cultured in F. proliferatum-contaminated
      soil, and the bulbs were screened for infection with F. proliferatum and for the
      occurrence of fumonisins by LC-MS. F. proliferatum was detectable in the garlic
      tissue, and all samples contained FB(1) (26.0-94.6 ng/g). This is the first
      report of the natural occurrence of FB(1) in German asparagus spears, and these
      findings suggest a potential for natural contamination of garlic bulbs with
      fumonisins.

PMID- 11982399
TI  - Identification and quantification of flavonol glycosides in almond seedcoats
      using MALDI-TOF MS.
AB  - Interest in the molecular composition of almonds is growing, due to their
      popularity in a wide variety of food formulations. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a
      powerful new technique that can be used to rapidly identify and quantify possible
      bioactive compounds in these popular tree nuts. Four flavonol glycosides were
      identified in almond seedcoats for the first time: isorhamnetin rutinoside,
      isorhamnetin glucoside, kaempferol rutinoside, and kaempferol glucoside. A MALDI
      TOF MS methodology was developed using rutin (quercetin-3-rutinoside) as an
      internal standard to quantitatively determine each of the four flavonol
      glycosides. Results of MALDI-TOF MS analysis were verified by high performance
      liquid chromatography.

PMID- 11982400
TI  - Antiradical efficiency of Maillard reaction mixtures in a hydrophilic media.
AB  - The Maillard reaction (MR) has a clear impact in food science, nutrition, and
      medical research. Free radical scavenging capacities of several MR mixtures made
      from single combinations of glucose or lactose and amino acids (gly, his, lys,
      trp, met, and cys) were evaluated by using the N,N-dimethyl-p-phenylenediamine
      radical cation assay. Medium-roasted coffee brew was used as reference of a
      thermally processed food. A novel approach has been applied in order to get more
      information about the kinetic behavior of the radical scavenging properties of MR
      mixtures in a watery environment. Antiradical efficiency (AE) concept has been
      applied, and it takes into consideration the reaction time, apart from the amount
      of antioxidant necessary to decrease by 50% the radical initial concentration
      (EC(50)). Cysteine and histidine reveal as powerful amino acids to exert a high
      AE in the MR mixtures. No relationship between AE parameter and browning was
      observed.

PMID- 11982401
TI  - Analysis of tobacco-specific nitrosamines in Moldovan cigarette tobacco.
AB  - Tobacco-specific nitrosamines (TSNA) are among the most important and abundant
      strongly carcinogenic agents in unburned tobacco. It has been established that 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lung tumors in rodents
      independent of the route of administration. N'-Nitrosonornicotine (NNN) causes
      tumors of the esophagus and nasal cavity in rats, lung in mice, and respiratory
      tract in hamsters. Although the manufacturing of cigarettes is an important
      domain of Moldovan industry, there are no reports in the literature on TSNA
      analysis in Moldovan tobacco. The main purpose of the present study was an
      initial evaluation of TSNA levels in Moldovan cigarette tobacco. Eighteen brands
      of Moldovan cigarettes, representing 78% of all brands produced in Moldova, were
      analyzed. Four TSNA-NNN, NNK, N'-nitrosoanatabine (NAT), and N'-nitrosoanabasine
      (NAB)-were analyzed by gas chromatography with nitrosamine selective detection
      (GC-TEA). Levels of TSNA in most Moldovan cigarettes were substantially lower
      than in American brands. Mean levels of NNN in three commercial American brands
      were 3.32 +/- 0.88 (SD) microg/g as compared to 0.579 +/- 0.548 microg/g, range
      0.093-2.09 microg/g (N = 18), in the cigarettes produced in Moldova. For NNK and
      NAT, mean levels in the American brands were 1.57 +/- 0.178 and 1.99 +/- 0.579
      microg/g, respectively, while the corresponding values for Moldovan cigarettes
      were 0.193 +/- 0.089, range 0.104-0.484 microg/g, and 0.160 +/- 0.114 microg/g,
      range 0.055-0.481 microg/g. The highest levels of NNN-1.10-2.09 microg/g-were
      observed in "American type" cigarettes manufactured from high-quality tobacco.
      The results of this study should be useful in heightening the awareness of the
      dangers of smoking in Moldova and can be envisioned as the initial step in the
      control of tobacco-related cancer in this republic.

PMID- 11982402
TI  - Immobilization of yeast cells with polymeric carrier cross-linked using radiation
      technique.
AB  - Various compositions of 2-hydroxyethacrylate (HEA) and methoxy polyethylene
      glycol methacrylate (M23G) monomers were irradiated by gamma-rays at low
      temperature (-78 degrees C) to synthesize polymer carriers for effectively
      immobilizing yeast cells. The yeast cells were immobilized by cell adhesion
      onto/in these polymers. The ethanol productivity of immobilized yeast cells with
      the polymer carriers was higher than that of free cells, increasing by 1-3 times.
      However, the ethanol productivity of immobilized yeast with the polymer carrier
      resulting from 7%/7% (HEA/M23G) monomer was low, comparatively. The effect of
      adding cross-linking reagent (4G) to the low concentration of HEA/M23G monomers
      on the activity of yeast cells immobilized with the cross-linked carriers by
      radiation polymerization was investigated. The ethanol productivity of
      immobilized cells with the carriers, which were cross-linked by adding 3-6% 4G to
      the low concentration of HEA/M23G monomer, was increased by 20-30%, because the
      pore size, network structure, and mechanical strength of the polymer carriers was
      well adjusted and cell leakage from the polymer carriers decreased. The
      relationship between the ethanol productivity of immobilized yeast cells and the
      interior structure of polymer carriers is discussed and indicated that the
      interior structure of polymer carriers is crucial for effective immobilization of
      yeast cells.

PMID- 11982403
TI  - Advantages of using non-isothermal bioreactors in agricultural waste water
      treatment by means of immobilized urease. Study on the influence of spacer length
      and immobilization method.
AB  - The behavior of three different catalytic membranes, obtained by immobilizing
      urease on nylon sheets chemically grafted with methyl methacrylate, was studied
      in a bioreactor operating under isothermal and non-isothermal conditions.
      Membrane activation was carried out by condensation or acyl azide reaction, and
      spacers of different lengths, such as hexamethylendiamine or hydrazine, were
      used. Under isothermal conditions, the activities of the catalytic membranes and
      soluble urease were characterized as a function of pH, temperature, and urea
      concentration. Both enzyme forms showed the same optimum pH, whereas the optimum
      temperature was lower for the immobilized enzymes. The spacer length appeared to
      determine broader pH- and temperature-activity profiles for the urease
      derivatives. The apparent K(m) values of the insoluble urease were dependent on
      membrane type and were higher than those of the soluble counterpart, thus
      indicating an affinity loss for urea. Under non-isothermal conditions, all
      membranes exhibited an increase of percentage activity proportional to the
      applied temperature difference and decreasing with the increase of urea
      concentrations. A decrease of the apparent K(m) was also observed. These results
      suggest that substrate diffusion limitations due to the immobilization process
      can be overcome in the presence of temperature gradients. In addition, the
      remarkable reduction of the production times supports the use of non-isothermal
      bioreactors for the treatment of urea-polluted waste waters.

PMID- 11982404
TI  - Cooperative action of alpha-glucanotransferase and maltogenic amylase for an
      improved process of isomaltooligosaccharide (IMO) production.
AB  - Maltogenic amylase and alpha-glucanotransferase (alpha-GTase) were employed in an
      effort to develop an efficient process for the production of
      isomaltooligosaccharides (IMOs). Bacillus stearothermophilus maltogenic amylase
      (BSMA) and alpha-GTase from Thermotoga maritima were overexpressed in Escherichia
      coli using overexpression vectors. An IMO mixture containing 58% of various IMOs
      was produced from liquefied corn syrup by the hydrolyzing and transglycosylation
      activities of BSMA alone. When BSMA and alpha-GTase were reacted simultaneously,
      the IMO content increased to 68% and contained relatively larger IMOs compared
      with the products obtained by the reaction without alpha-GTase. Time course
      analysis of the IMO production suggested that BSMA hydrolyzed maltopentaose and
      maltohexaose most favorably into maltose and maltotriose and transferred the
      resulting molecules simultaneously to acceptor molecules to form IMOs. alpha
      GTase transferred donor sugar molecules to the hydrolysis products such as
      maltose and maltotriose to form maltopentaose, which was then rehydrolyzed by
      BSMA as a favorable substrate.

PMID- 11982405
TI  - Composition and stability of herring oil recovered from sorted byproducts as
      compared to oil from mixed byproducts.
AB  - Herring oils produced from three different types of byproducts, only heads,
      mixed, and headless byproducts, were compared. Heads byproducts and its oil
      presented the highest oxidation levels and the lowest alpha-tocopherol content.
      Heads contained the lowest polyunsaturated fatty acids content and the highest
      amount of saturated fatty acids. No significant differences were found between
      the fatty acid composition of the mixed and the headless either in byproducts or
      in its oil. The oil was stored at two different temperatures (20 and 50 degrees
      C). Testing general linear models showed that oxidation was related to the
      peroxide value with a positive significant effect of the temperature, while the
      free fatty acids' model was more complex, with significant contribution of all of
      the effects studied. Fluorescence measurement was the one that correlated best
      with the oxidation progress.

PMID- 11982406
TI  - Furosine: a suitable marker for assessing the freshness of royal jelly.
AB  - Fifteen commercial samples of royal jelly, consisting of 10 imported samples, and
      5 samples of known origin obtained freshly harvested from beekeepers, were
      analyzed for protein, lysine, and furosine content. In addition, a commercial
      sample of royal jelly, at the beginning of its commercial shelf life, was stored
      for 10 months both at 4 degrees C and at room temperature in order to assess the
      development of the Maillard reaction (furosine) and relative nutritional damage
      (blocked lysine). The commercial royal jelly products contained different amounts
      of furosine, ranging from 37.1 to 113.3 mg/100 g protein, evidence of different
      storage times and conditions. The average furosine content of the royal jelly
      samples of known origin and harvesting was significantly lower than that of the
      imported samples (41.7 versus 73.6 mg/100 g protein, respectively). With regard
      to shelf life, furosine content increased significantly from 72.0 mg/100 g
      protein to 500.8 mg/100 g protein after 10 months of storage at room temperature,
      while it increased to a much lower level (100.5 mg/100 g protein) when the royal
      jelly was stored at 4 degrees C. However, nutritional damage, expressed as
      blocked lysine (calculated indirectly from the furosine content), was minor or
      negligible, 11.9 and 2.3% of total lysine, in samples stored at room temperature
      and at 4 degrees C, respectively. Lysine was determined by an innovative
      procedure based on high-performance anion-exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD). The results showed that furosine is a
      suitable index for assessing the quality and freshness of royal jelly.

PMID- 11982407
TI  - Partition behavior of virgin olive oil phenolic compounds in oil-brine mixtures
      during thermal processing for fish canning.
AB  - The chemical modifications and partitioning toward the brine phase (5% salt) of
      major phenol compounds of extra virgin olive oil (EVOO) were studied in a model
      system formed by sealed cans filled with oil-brine mixtures (5:1, v/v) simulating
      canned-in-oil food systems. Filled cans were processed in an industrial plant
      using two sterilization conditions commonly used during fish canning. The
      partitioning of phenolic compounds toward brine induced by thermal processing was
      studied by reversed-phase high-performance liquid chromatographic analysis of the
      phenol fraction extracted from oils and brine. Hydroxytyrosol (1), tyrosol (2),
      and the complex phenolic compounds containing 1 and 2 (i.e., the dialdehydic form
      of decarboxymethyl oleuropein aglycon 3, the dialdehydic form of decarboxymethyl
      ligstroside aglycon 4, and the oleuropein aglycon 6) decreased in the oily phase
      after sterilization with a marked partitioning toward the brine phase. The
      increase of the total amount of 1 and 2 after processing, as well as the presence
      of elenolic acid 7 released in brine, revealed the hydrolysis of the ester bond
      of hydrolyzable phenolic compounds 3, 4, and 6 during thermal processing. Both
      phenomena (partitioning toward the water phase and hydrolysis) contribute to
      explain the loss of phenolic compounds exhibited by EVOO used as filling medium
      in canned foods, as well as the protection of n-3 polyunsaturated fatty acids in
      canned-in-EVOO fish products.

PMID- 11982408
TI  - Increasing resistance against Phytophthora citrophthora in tangelo Nova fruits by
      modulating polymethoxyflavones levels.
AB  - The effect of 6-benzylaminopurine on polymethoxyflavone levels in tangelo Nova
      fruits and the possible participation of these secondary metabolites in defense
      mechanisms against Phytophthora citrophthora are studied. The in vitro study of
      the inhibitory effect of these compounds on fungal growth reveals that nobiletin
      is the most active agent followed by sinensetin, heptamethoxyflavone, and
      tangeretin. Treatment with 100 ppm of 6-benzylaminopurine increased the levels of
      these polymethoxyflavones in this Citrus hybrid and also enhanced the in vivo
      resistance of the fruit to the fungus by approximately 60%.

PMID- 11982409
TI  - Comparison of different egg albumen fractions as sources of ovomucin.
AB  - Ovomucin was fractionated from whole egg albumen, thick egg albumen, liquid egg
      albumen, and a liquid egg albumen filtration byproduct by using the isoelectric
      precipitation method. The amounts of ovomucin measured in the above-mentioned
      fractions were 280, 340, 500, and 520 mg per 100 g of albumen, respectively.
      There was great variation between the beta-ovomucin contents of the different
      albumen fractions. Whole egg albumen contained about 25 mg of beta-ovomucin in
      100 g of albumen, whereas thick egg albumen, liquid egg albumen, and the
      filtration byproduct contained about 1.5, 3, and 5 times more beta-ovomucin,
      respectively, as compared to whole egg albumen. The results indicate that both
      the liquid egg albumen fraction and especially the filtration byproduct fraction
      appear to be potential sources of ovomucin when it is used as an ingredient for
      functional foods.

PMID- 11982410
TI  - Recovery and characterization of the metal polymeric organic fraction (polymerin)
      from olive oil mill wastewaters.
AB  - A dark and complex metal polymeric organic mixture, named polymerin, was
      recovered from olive oil mill wastewaters (OMWW) and characterized by chemical
      analysis, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS),
      and atomic absorption spectrometry (AAS). Polymerin proved to be composed of
      carbohydrates (52.40 mg 100(-1), w/w), melanin (26.14 mg 100(-1)), and proteins
      (10.40 mg 100(-1)), and the respective composition of monosaccharides, phenols,
      and amino acids was determined. It also contained metals (11.06 mg 100(-1)),
      mainly K(+) and, to a lesser extent, Na(+), Ca(2+), Mg(2+), Zn(2+), Fe(3+), and
      Cu(2+), which were naturally bound and chelated through carboxylate anions and
      other characteristic nucleophilic functional groups naturally occurring in
      polymerin. The distribution of polymerin relative molecular size was assessed to
      be approximately between 500.0 and 2.0 kDa by calibrated molecular weight gel
      filtration chromatography, indicating also that a fraction consisted of protein,
      melanin, and polysaccharide, strongly aggregated to each other in a
      supramolecular status by a combination of covalent and hydrogen bonds and CH/Pi
      interactions, and another fraction of only free polysaccharide. Polymerin was
      transformed into a potassium salt deglycosylated derivative, named KSDpolymerin,
      which was also characterized by chemical analysis, DRIFTS, and AAS. KSDpolymerin
      consisted of carbohydrates (6.00 mg 100(-1)), melanin (52.49 mg 100(-1)), and
      proteins (35.40 mg 100(-1)), and the composition of monosaccharides, phenols, and
      amino acids was determined. It also contained metals (6.11 mg 100(-1)), mainly
      K(+) and to a lesser extent Na(+), Ca(2+), Mg(2+), Zn(2+) and Fe(3+), bound as in
      polymerin. All the organic components were strongly linked in a supramolecular
      aggregate status and the relative average molecular size proved to be 6.3 kDa.
      Finally, we briefly discuss the possible use of such polymerins in agriculture as
      bioamendments and macro- and microelement biointegrators and as a biofilter for
      toxic metal removal, in light of their similarity with humic acids.

PMID- 11982411
TI  - Sulfometuron incorporation in cationic micelles adsorbed on montmorillonite.
AB  - The aim of this study was to understand the interactions between alkylammonium
      cations present as monomers and micelles and a clay mineral, montmorillonite, to
      develop slow release formulations of anionic herbicides, such as sulfometuron
      (SFM) whose leaching in soils is an environmental and economic problem. In the
      proposed formulation the herbicide is incorporated in positively charged micelles
      of quaternary amine cations, which in turn adsorb on the negatively charged clay.
      The adsorption of hexadecyltrimethylammonium (HDTMA) and
      octadecyltrimethylammonium (ODTMA) on montmorillonite was studied above and below
      their critical micelle concentrations (CMC). At concentrations above the CMC, the
      loading exceeded the clay's cation exchange capacity (CEC) and indicated higher
      affinity of the cation with the longer alkyl chain. An adsorption model could
      adequately simulate adsorption at concentrations below the CMC, and yield fair
      predictions for the effect of ionic strength. The model indicated that above the
      CMC adsorbed micelles contributed significantly to the amount of ODTMA adsorbed.
      Evidence for adsorption of ODTMA micelles on montmorillonite was provided by X
      ray diffraction, freeze-fracture electron microscopy, and dialysis bag
      measurements. SFM was not adsorbed directly on the clay mineral, and adsorbed at
      low levels, when the organic cation was adsorbed as monomers. In contrast, a
      large fraction of SFM adsorbed on the clay mineral when incorporated in micelles
      that adsorbed on the clay.

PMID- 11982412
TI  - Slow-release formulations of sulfometuron incorporated in micelles adsorbed on
      montmorillonite.
AB  - The design and tests of slow-release formulations of sulfometuron (SFM), an
      anionic sulfonylurea herbicide, are described. The formulations are based on
      incorporation of the herbicide in octadecyltrimethylammonium (ODTMA) micelles,
      which adsorb on a clay mineral, montmorillonite. An optimization of
      herbicide/micelle clay ratios yielded high adsorption of SFM (95%), and at a 1%
      (w/w) water suspension only 0.5% of the adsorbed SFM was released at times
      varying from hours to 9 days. An analytical test in Seville soil showed that
      under excessive irrigation (400 mm) 100% of the commercial formulation leached,
      whereas the micelle-clay formulations showed only 50-65% elution. A plant
      bioassay in Rehovot soil showed that the commercial dispersible granule
      formulation (Oust, 75% ai sulfometuron methyl) yielded only 23% root elongation
      inhibition at the top 5 cm of the soil, whereas complete inhibition was achieved
      with the micelle-clay formulation. The detected concentration of SFM for the
      micelle-clay formulation at a depth of 15-20 cm was half of that detected for the
      commercial one, indicating a reduction in leaching when applying the micelle-clay
      formulation. A 10-fold reduction in the applied dose of SFM in the micelle-clay
      formulations resulted in good herbicidal activity of 60-87% inhibition. These
      characteristics make the new formulation promising from the environmental and
      economic points of view.

PMID- 11982413
TI  - Coriander essential oil composition from two genotypes grown in different
      environmental conditions.
AB  - The objective was to study the essential oil composition of coriander fruits in
      plants growing in environments differing in soil conditions and weediness level.
      Factorial field experiments were conducted in two locations from the Rolling
      Pampas, Argentina, and two coriander landraces (European and Argentinean) were
      tested under two levels of nitrogen fertilization and weediness. Data were
      evaluated with uni- and multivariate techniques. The variation in the oil
      composition was related to the relative proportion of the constituents and not to
      the presence/absence of a particular component. Weather conditions in 1997
      favored linalool and camphor in both landraces. Location, fertilization, and
      weediness also affected the chemical profile. The European landrace showed a more
      stable concentration of the major components than the Argentinean landrace. These
      results, which show the relationships between some environmental conditions and
      the essential oil composition, are useful in the development of innovative
      strategies aimed to improve oil composition and to manage crop pests.

PMID- 11982414
TI  - Furfural-cysteine model reaction in food grade nonionic oil/water microemulsions
      for selective flavor formation.
AB  - The thermal reaction between cysteine and furfural was investigated at 65 degrees
      C in five-component food grade oil/water (O/W) microemulsions of R-(+)
      limonene/ethanol, EtOH/water/propylene glycol, PG/Tween 60 as apart of a
      systematic study on the generation of aroma compounds by utilizing structured W/O
      and O/W fluids. The furfural-cysteine reaction led to the formation of unique
      aroma compounds such as 2-furfurylthiol (FFT), 2-(2-furanyl)thiazolidine (main
      reaction product), 2-(2-furanyl)thiazoline, and N-(2-mercaptovinyl)-2-(2
      furanyl)thiazolidine. These products were determined and characterized by GC-MS.
      Enhancement in flavor formation is termed "microemulsion catalysis". The chemical
      reaction occurs preferably at the interfacial film, and therefore a pseudophase
      model was assumed to explain the enhanced flavor formation. The product internal
      composition is dictated by process conditions such as temperature, time, pH, and
      mainly the nature of the interface. Increasing water/PG ratio leads to a dramatic
      increase in the initial reaction rate (V(0)). V(0) increased linearly as a
      function of the aqueous phase content, which could be due to the increase in the
      interfacial concentration of furfural. Microemulsions offer a new reaction medium
      to produce selective aroma compounds and to optimize their formation.

PMID- 11982415
TI  - Characterization of some Allium hybrids by aroma precursors, aroma profiles, and
      alliinase activity.
AB  - Various Allium hybrids, obtained by the crossbreeding of Allium cepa (onion) as
      the mother plant and six taxonomically distant wild species obtained by embryo
      rescue, were investigated with special respect to their individual profiles of
      cysteine sulfoxides as well as enzymically and nonenzymically formed aroma
      substances. Alliinase (EC 4.4.1.4) catalyzes the conversion of odorless (+)-S
      alk(en)yl-L-cysteine sulfoxides into volatile thiosulfinates. These
      thiosulfinates were converted to a variety of sulfides by steam distillation.
      SPME-gas chromatography (GC) and high-performance liquid chromatography (HPLC)
      used for the analysis of aroma components and their precursors permitted a high
      sample throughput, so that numerous gene bank accessions and Allium breeding
      materials were analyzed within a comparatively short time. Cysteine sulfoxides as
      well as alliinase activity were found in all investigated samples at different
      levels, but (+)-S-methyl-L-cysteine sulfoxide (methiin) was the most abundant
      sulfoxide present. (+)-S-(trans-1-Propenyl)-L-cysteine sulfoxide (isoalliin) is
      typical for onion and was found in all investigated hybrids. The pattern of the
      other cysteine sulfoxides depended strongly on the parent plants used. The
      profile of aroma components corresponded with the related pattern of aroma
      precursors (cysteine sulfoxides). Successful hybridization was proven by randomly
      amplified polymorphic DNA analysis. Together with these established marker
      techniques, HPLC and SPME-GC analysis provide support to breeding projects
      designed to improve the health and aroma properties of Allium hybrids.

PMID- 11982416
TI  - Relationship between varietal amino acid profile of grapes and wine aromatic
      composition. Experiments with model solutions and chemometric study.
AB  - Synthetic solutions containing amino acids, sugar, water, and yeast nutrients
      have been fermented by Saccharomyces cerevisiae, and the volatile composition of
      the fermented media has been analyzed by GC. Eleven amino acid compositions
      imitating the characteristic amino acid profile of 11 different grape varieties
      were tested. Significant differences in the levels of some important volatile
      compounds (ethanol, ethyl acetate, acetic acid, higher alcohols and some of their
      acetates, methionol, isobutyric acid, ethyl butyrate, and hexanoic and octanoic
      acids) were found. The levels of some of the volatile compounds are well
      correlated with the aromatic composition of wines made with grapes of the same
      varieties. A multiple linear regression study produced good models for most of
      the odorants for which the level was related to the must amino acid composition.
      Partial least-squares regression models confirm that amino acid composition
      explains a high proportion of the variance in the volatile composition and show
      that the relationship between both sets of variables is highly multivariate.
      According to the different models, the levels of some byproducts of fatty acid
      synthesis are related to threonine and serine, the level of beta-phenyletanol is
      closely related to the level of phenylalanine, and methionol is strongly
      correlated to the must methionine contents. The addition of selected amino acids
      to different musts confirms the previous observations.

PMID- 11982417
TI  - Characterization of the aroma of a meatlike process flavoring from soybean-based
      enzyme-hydrolyzed vegetable protein.
AB  - Defatted soybean meal was converted into enzyme-hydrolyzed vegetable protein (E
      HVP) using the proteolytic enzyme Flavorzyme. Total free amino acids increased by
      40-fold after enzyme hydrolysis, with leucine being the most abundant, followed
      by phenylalanine, lysine, glutamine/glutamic acid, and alanine. Volatile
      components from a meatlike process flavoring made from E-HVP were isolated by
      direct solvent extraction (DSE)-high vacuum transfer (HVT), dynamic headspace
      sampling and static headspace sampling and analyzed by gas chromatography (GC)
      mass spectrometry and GC-olfactometry. Aroma extract dilution analysis was used
      to establish a flavor dilution chromatogram of the DSE-HVT extract. Results of
      these complementary techniques indicated the importance of odorants of high
      (hydrogen sulfide and methanethiol), intermediate (2-methyl-3-furanthiol, 3
      mercapto-2-pentanone, 2-furanmethanethiol, and 3-(methylthiol)propanal) and low
      volatility (maltol and Furaneol) in the overall aroma of the meatlike process
      flavoring.

PMID- 11982418
TI  - Characteristic odor components of Citrus sphaerocarpa Tanaka (Kabosu) cold
      pressed peel oil.
AB  - The volatile components of Citrus sphaerocarpa Tanaka (Kabosu) cold-pressed peel
      oil were investigated by chemical and sensory analyses. Monoterpene hydrocarbons
      (more than 94.6%) were predominant in Kabosu peel oil, with limonene and myrcene
      accounting for the major proportions (70.5% and 20.2%, respectively). The Kabosu
      oxygenated fraction was characterized by quantitative abundance in aldehydes and
      a relatively wide variety of alcohols. The weight percentages of aldehydes,
      alcohols, and esters in Kabosu cold-pressed oil were 1.3%, 0.1%, and 0.1%,
      respectively. Aroma extract dilution analysis was employed for determination of
      the odors of Kabosu volatile components, flavor dilution factors, and relative
      flavor activities. Gas chromatography/olfactometry using Kabosu cold-pressed oil
      and its oxygenated fraction completed by a chiral analysis revealed that (R)-(+)
      citronellal is a characteristic element of Kabosu peel oil odor. Careful sniff
      testing demonstrated that aqueous solutions of both 0.25% and 0.016% (R)-(+)
      citronellal gave an odor similar to that of Kabosu.

PMID- 11982419
TI  - Identification of radical scavengers in sweet grass (Hierochloe odorata).
AB  - Extracts from aerial parts of sweet grass (Hierochloe odorata) were active DPPH
      free radical scavengers. The active compounds were detected in extract fractions
      using HPLC with on-line radical scavenging detection. After multistep
      fractionation of the extract, two new natural products possessing radical
      scavenging activity were isolated, and their structures were elucidated by NMR
      and MS. They were identified as 5,8-dihydroxybenzopyranone and 5-hydroxy-8-O-beta
      D-glucopyranosyl-benzopyranone. Activities of the compounds isolated were tested
      by DPPH and ABTS free radical scavenging assays, and compared with the known
      natural antioxidant rosmarinic acid and Trolox.

PMID- 11982420
TI  - Purification and glycosylation analysis of an acidic pectin methylesterase in
      jelly fig (Ficus awkeotsang) achenes.
AB  - An acidic pectin methylesterase (PME) is responsible for the gelation of water
      extract from jelly fig (Ficus awkeotasang) achenes. A new, fast and efficient,
      method has been developed to purify this acidic PME. The method includes
      preparing jelly curd by traditional hand washing, extracting proteins from the
      curd, and separating PME by anion-exchanger. The purified PME exists as a monomer
      of 38 kDa determined by gel filtration, and exerts enzymatic activity over a
      broad pH range, particularly in acidic environments where most known PME enzymes
      from various species are inactivated. Chemical staining and enzymatic cleavage
      suggest that the jelly fig PME is an N-linked glycoprotein. Fluorophore-assisted
      carbohydrate electrophoresis reveals that the polysaccharide of this glycoprotein
      putatively consists of 22 hexoses including 16 mannose, 4 N-acetylglucosamine,
      and 2 galactose residues.

PMID- 11982421
TI  - Antioxidant and antiproliferative activities of raspberries.
AB  - Raspberries are rich in phenolic phytochemicals. To study the health benefits of
      raspberries, four fresh raspberry varieties (Heritage, Kiwigold, Goldie, and
      Anne) were evaluated for total antioxidant and antiproliferative activities. The
      total amount of phenolics and flavonoids for each of the four raspberry varieties
      was determined. The Heritage raspberry variety had the highest total phenolic
      content (512.7 +/- 4.7 mg/100 g of raspberry) of the varieties measured followed
      by Kiwigold (451.1 +/- 4.5 mg/100 g of raspberry), Goldie (427.5 +/- 7.5 mg/100 g
      of raspberry), and Anne (359.2 +/- 3.4 mg/100 g of raspberry). Similarly, the
      Heritage raspberry variety contained the highest total flavonoids (103.4 +/- 2.0
      mg/100 g of raspberry) of the varieties tested, followed by Kiwigold (87.3 +/-
      1.8 mg/100 g of raspberry), Goldie (84.2 +/- 1.8 mg/100 g of raspberry), and Anne
      (63.5 +/- 0.7 mg/100 g of raspberry). The color of the raspberry juice correlated
      well to the total phenolic, flavonoid, and anthocyanin contents of the raspberry.
      Heritage had the highest a/b ratio and the darkest colored juice, and the Anne
      variety showed the lowest phytochemical content and the palest color. Heritage
      raspberry variety had the highest total antioxidant activity, followed by
      Kiwigold and Goldie, and the Anne raspberry variety had the lowest antioxidant
      activity of the varieties tested. The proliferation of HepG(2) human liver cancer
      cells was significantly inhibited in a dose-dependent manner after exposure to
      the raspberry extracts. The extract equivalent to 50 mg of Goldie, Heritage, and
      Kiwigold fruit inhibited the proliferation of those cells by 89.4 +/- 0.1, 88 +/-
      0.2, and 87.6 +/- 1.0%, respectively. Anne had the lowest antiproliferative
      activity of the varieties measured but still exhibited a significant inhibition
      of 70.3+/- 1.2% with an extract equivalent to 50 mg of fruit. The antioxidant
      activity of the raspberry was directly related to the total amount of phenolics
      and flavonoids found in the raspberry (p < 0.01). No relationship was found
      between antiproliferative activity and the total amount of phenolics/flavonoids
      found in the same raspberry (p > 0.05).

PMID- 11982422
TI  - Enzymatic modification of pectin to increase its calcium sensitivity while
      preserving its molecular weight.
AB  - A commercial high-methoxy citrus pectin was treated with a purified salt
      independent pectin methylesterase (PME) isozyme isolated from Valencia orange
      peel to prepare a series of deesterified pectins. A series of alkali-deesterified
      pectins was also prepared at pH 10 under conditions permitting beta-elimination.
      Analysis of these pectins using high-performance size exclusion chromatography
      (HPSEC) with on-line multiangle laser light-scattering, differential viscometer,
      and refractive index (RI) detectors revealed no reduction in weight-average
      molecular weight (M(w); 150000) in the PME-treated pectin series, whereas a 16%
      reduction in intrinsic viscosity (IV) occurred below a degree of esterification
      (DE) of 47%. In contrast, alkali deesterification rapidly reduced both M(w) and
      IV to less than half of that observed for untreated pectin. PME treatment of a
      non-calcium-sensitive citrus pectin introduced calcium sensitivity with only a 6%
      reduction in the DE. Triad blocks of unesterified galacturonic acid were observed
      in (1)H nuclear magnetic resonance spectra of this calcium-sensitive pectin
      (CSP). These results demonstrate that the orange salt-independent PME isozyme
      utilizes a blockwise mode of action. This is the first report of the preparation
      of a CSP by PME treatment without significant loss of the pectin's M(w) due to
      depolymerization.

PMID- 11982423
TI  - Correlations between biochemical characteristics and foam-forming and 
      stabilizing ability of whey and casein hydrolysates.
AB  - Whey protein and casein were hydrolyzed with 11 commercially available enzymes.
      Foam properties of 44 samples were measured and were related to biochemical
      properties of the hydrolysates using statistical data analysis. All casein
      hydrolysates formed high initial foam levels, whereas whey hydrolysates differed
      in their foam-forming abilities. Regression analysis using the molecular weight
      distribution of whey hydrolysates as predictors showed that the hydrolysate
      fraction containing peptides of 3-5 kDa was most strongly related to foam
      formation. Foam stability of whey hydrolysates and of most casein hydrolysates
      was inferior to that of the intact proteins. The foam stability of casein
      hydrolysate foams was correlated to the molecular weight distribution of the
      hydrolysates; a high proportion of peptides >7 kDa, composed of both intact
      casein and high molecular weight peptides, was positively related to foam
      stability.

PMID- 11982424
TI  - Effects of ethanol on structure and solubility of potato proteins and the effects
      of its presence during the preparation of a protein isolate.
AB  - In this study, a protein isolate with a high solubility at neutral pH was
      prepared from industrial potato juice by precipitation at pH 5 in the presence of
      ethanol. The effects of ethanol itself and the effects of its presence during
      precipitation on the properties of various potato protein fractions were
      examined. The presence of ethanol significantly reduced the denaturation
      temperature of potato proteins, indicating that the preparation of this potato
      protein isolate should be performed at low temperature in order to retain a high
      solubility. In the presence of ethanol, the thermal unfolding of the tertiary and
      the secondary structure of patatin was shown to be almost completely independent.
      Even at 4 degrees C, precipitation of potato proteins in the presence of ethanol
      induced significant conformational changes. These changes did, however, only
      result in minor changes in the solubility of the potato protein fractions as a
      function of pH and heat treatment temperature.

PMID- 11982425
TI  - Effect of emulsifier on oxidation properties of fish oil-based structured lipid
      emulsions.
AB  - The effects of the emulsifiers lecithin, Tween 20, whey protein isolate, mono
      /diacylglycerols, and sucrose fatty acid ester on oxidation stability of a model
      oil-in-water emulsion prepared with enzymatically synthesized menhaden oil
      caprylic acid structured lipid were evaluated. Oxidation was monitored by
      measuring lipid hydroperoxides, thiobarbituric acid reactive substances, and the
      ratio of combined docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)
      contents to palmitic acid in the emulsion. After high-pressure homogenization,
      all emulsions, except those prepared with lecithin, had similar droplet size
      distributions. All structured lipid emulsions, except for the lecithin-stabilized
      emulsions, were stable to creaming over the 48-day period studied. Emulsifier
      type and concentration affected oxidation rate, with 0.25% emulsifier
      concentration generally having a higher oxidation rate than 1% emulsifier
      concentration. Overall, oxidation did not progress significantly enough in 48
      days of storage to affect DHA and EPA levels in the emulsion.

PMID- 11982426
TI  - Natural variations of precursors in pig meat affect the yield of heterocyclic
      amines--effects of RN genotype, feeding regime, and sex.
AB  - Pig meat shows natural variations in the concentrations of precursors of
      heterocyclic amines (HCAs), which may affect formation of HCAs in cooked pig
      meat. To study this, 26 pigs with an inherent genetic variation (carriers and
      noncarriers of the RN(-) allele) were subjected to different feeding regimes
      (conventional feed compared with feed composed according to organic standards).
      In addition, the effect of sex (castrated males or females) was considered when
      assessing chemical and technological meat quality parameters. Concentrations of
      precursors of HCAs, i.e., creatine, residual glycogen, dipeptides, and free amino
      acids, were analyzed in the raw meat, and the levels of some HCAs (4,8-DiMeIQx,
      MeIQx, PhIP, harman, and norharman) were then determined in fried meat patties
      prepared from these pigs. The RN genotype most affected technological meat
      quality parameters and the level of precursors of HCAs, especially the level of
      residual glycogen, where carriers of the RN(-) allele showed levels four times as
      high as those of noncarriers (75.3 +/- 2.6 compared with 17.2 +/- 2.4 micromol/g
      meat, least-squares means +/- SE). The increased level of residual glycogen
      resulted in about 50% lower amounts of total mutagenic HCAs in cooked meat
      compared with cooked meat from normal pigs. Fried meat from carriers of the RN(-)
      allele obtained darker crust color than meat from noncarriers. Feeding regime and
      sex did not significantly affect the chemical composition of the meat or the
      formation of HCAs.

PMID- 11982427
TI  - Influence of Maillard reaction products on DNA damage in human lymphocytes.
AB  - The effect of Maillard reaction products (MRPs) on induced DNA damage in human
      lymphocytes was investigated using single-cell gel electrophoresis (comet assay).
      Three MRPs, Xyl-Lys MRP, Glu-Lys MRP, and Fru-Lys MRP, were prepared by heating
      lysine with xylose, glucose, and fructose, respectively, at pH 9.0 and 100
      degrees C for 3 h and called undialyzed MRPs. The prepared MRPs were further
      dialyzed, and three undialyzable MRPs were obtained. The undialyzed MRPs caused
      significant (p < 0.05) DNA damage in human lymphocytes at a concentration of 0.05
      0.1 mg/mL by the comet assay. Compared with the control, the undialyzable Xyl-Lys
      MRP and Glu-Lys MRP caused significant DNA damage in human lymphocytes at a
      concentration >0.1 mg/mL, whereas Fru-Lys MRP did so at a concentration >0.2
      mg/mL. Moreover, undialyzed MRPs caused less DNA damage than did undialyzable
      MRPs. The undialyzable MRPs did not affect the activity of glutathione peroxidase
      or lipid peroxidation in human lymphocytes at a concentration of 0.05-0.8 mg/mL.
      However, these three undialyzable MRPs decreased the glutathione (GSH) contents
      and the activities of GSH reductase and catalase in human lymphocytes. On the
      basis of the results of the formation of 8-hydroxy-2'-deoxyguanosine, radicals,
      and hydrogen peroxide, the radicals might play an important role in the DNA
      damage in human lymphocytes induced by these MRPs in this reaction system.

PMID- 11982428
TI  - Inclusion complex of conjugated linoleic acid (CLA) with cyclodextrins.
AB  - Conjugated linoleic acid (CLA) inclusion complexes with alpha-cyclodextrin (alpha
      CD), beta-cyclodextrin (beta-CD), and gamma-cyclodextrin (gamma-CD) (designated
      CLA/CDs inclusion complexes) were prepared to determine the mole ratio of CLA
      complexed with CDs and the oxidative stability of CLA in the CLA/CDs inclusion
      complexes. When measured by GC, (1)H NMR, and T(1) value analyses, 1 mole of CLA
      was complexed with 5 mol of alpha-CD, 4 mol of beta-CD, and 2 mol of gamma-CD.
      The oxidation of CLA induced at 35 degrees C for 80 h was completely prevented by
      the formation of CLA/CDs inclusion complexes.

PMID- 11982429
TI  - Maillard reaction of D-glucose: identification of a colored product with
      conjugated pyrrole and furanone rings.
AB  - Formation of colored compounds during the Maillard reaction of D-glucose with
      butylammonium acetate in aqueous solution has been investigated. Butylamine was
      used as a model compound analogous to the lysine side chains of proteins. The
      previously unknown, yellow product, 4-hydroxy-5-methyl-2-(N-butyl-3-hydroxy-5-(2
      hydroxyethyl)pyrrolyl-2-methylidene)-2H-furan-3-one (1a), was isolated from the
      reaction mixtures and identified by spectroscopic data.

PMID- 11982430
TI  - Gelling properties of heat-denatured beta-lactoglobulin aggregates in a high-salt
      buffer.
AB  - Thermal denaturation, rheological, and microstructural properties of gels
      prepared from native beta-lactoglobulin (beta-LG) and preheated or heat-denatured
      beta-LG (HDLG) aggregates were compared. The HDLG was prepared by heating
      solutions of 4% beta-LG in deionized water, pH 7.0, at 80 degrees C for 30 min
      and then diluted to the desired concentration in 0.6 M NaCl and 0.05 M phosphate
      buffer at pH 6.0, 6.5, and 7.0. When reheated to 71 degrees C, HDLG formed a gel
      at a concentration of 2% protein. At pH 7.0, 3% HDLG gelled at 52.5 degrees C and
      had a storage modulus (G') of 2200 Pa after cooling. beta-LG (3%) in 0.6 M NaCl
      and 0.05 M phosphate buffer, pH 7.0, did not gel when heated to 71 degrees C. The
      gel point of 3% HDLG decreased by 10.5 degrees C and the G' did not change when
      the pH was decreased to 6.0. The HDLG gel microstructure was composed of strands
      and clumps of small globular aggregates in contrast to beta-LG gels, which
      contained a particulate network of compacted globules. The HDLG formed a gel at a
      lower concentration and lower temperature than beta-LG in the high-salt buffer,
      suggesting an application in meat systems or other food products prepared with
      salt and processed at temperatures of < or =71 degrees C.

PMID- 11982431
TI  - Antioxidant activity of phenolic compounds isolated from Mesona procumbens Hemsl.
AB  - The antioxidant activity of phenolic compounds isolated from Mesona procumbens
      Hemsl. (Hsian-tsao) was investigated. Hsian-tsao was extracted with various
      solvents, and the results showed that the fraction treated with acidic ethyl
      acetate (pH 2) possessed large amounts of phenolic compounds and a strong
      antioxidant activity on peroxidation of linoleic acid. The antioxidant activity
      (inhibition of peroxidation, IP%) of the acidic ethyl acetate of Hsian-tsao
      extract at 50 microg/mL (98.9%) was stronger than those of 50 microg/mL alpha
      tocopherol (78%) and BHA at 10 microg/mL (90%). When fractionated with Amberlite
      XAD-7 gel chromatography, the acidic ethyl acetate fraction of Hsian-tsao extract
      was separated into four subfractions (A-D). Subfraction B, with high yield and
      strong antioxidant activity, was further isolated and purified and then
      identified as containing protocatechuic acid, p-hydroxybenzoic acid, vanillic
      acid, caffeic acid, and syringic acid by means of UV, EI-MS, and (1)H and (13)C
      NMR. The antioxidant capability of isolated compounds was also determined using
      the thiocyanate system and the erythrocyte ghost system. The results indicate
      that the phenolic acids could be important antioxidant components in Hsian-tsao,
      among which caffeic acid with the highest antioxidant activity and the greatest
      content is most important.

PMID- 11982432
TI  - Kinetics of reduction of ferrylmyoglobin by (-)-epigallocatechin gallate and
      green tea extract.
AB  - The hypervalent heme pigment ferrylmyoglobin, a potential prooxidant in muscle
      tissue and meat, is efficiently reduced by epigallocatechin gallate (EGCG) from
      green tea and by green tea polyphenol extract (GTP) in neutral or moderately
      acidic aqueous solution (0.16 M NaCl) to yield metmyoglobin in two parallel
      processes. The second-order rate constant for direct reduction at pH 7.4 and 25
      degrees C was found to have the value 1170 +/- 83 M(-1).s(-1) and activation
      parameters DeltaH(#) = 70.6 +/- 7.2 kJ.mol(-1) and DeltaS(#) = 50.7 +/- 24.1
      J.mol(-1).K(-1) for EGCG and the value 2300 +/- 77 M(-1).s(-1) and parameters
      DeltaH(#) = 60.6 +/- 2.6 kJ.mol(-1) and DeltaS(#) = 23 +/- 9 J.mol(-1).K(-1) for
      GTP (based on EGCG concentration). For decreasing pH, the rate increased
      moderately due to a parallel reduction of protonated ferrylmyoglobin. At
      physiological pH, EGCG is more efficient in deactivating ferrylmyoglobin than
      other plant phenols investigated, and the relatively high enthalpy and positive
      entropy of activation suggest an outer-sphere electron transfer mechanism. The
      interaction between EGCG and other tea catechins in GTP could be responsible for
      the even stronger ability for GTP to deactivate ferrylmyoglobin.

PMID- 11982433
TI  - Triacylglycerols, glycerophospholipids, tocopherols, and tocotrienols in berries
      and seeds of two subspecies (ssp. sinensis and mongolica) of Sea Buckthorn
      (Hippophae rhamnoides).
AB  - Berries and seeds of two subspecies (ssp. sinensis and mongolica) of sea
      buckthorn (Hippophae rhamnoides L.) were compared in terms of triacylglycerols,
      glycerophospholipids, tocopherols, and tocotrienols. The berries of ssp.
      mongolica contained less oleic acid (4.6 vs 20.2%, p < 0.001) and more palmitic
      (33.9 vs 27.4%, p < 0.01) and palmitoleic (32.8 vs 21.9%, p < 0.05) acids in
      triacylglycerols than those of ssp. sinensis. The proportions of linoleic acid
      (32.1 vs 22.2%, p < 0.01, in berries; 47.7 vs 42.7%, p < 0.05, in seeds) and
      palmitic acid (21.1 vs 16.4%, p < 0.001, in berries; 17.0 vs 14.1%, p < 0.05, in
      seeds) in glycerolphospholipids were higher in ssp. mongolica than in ssp.
      sinensis, and vice versa with oleic acid (4.3 vs 18.5% in berries, 10.0 vs 22.2%
      in seeds, p < 0.001). A higher proportion of alpha-linolenic acid was also found
      in the glycerophospholipids of ssp. sinensis berries (16.2 vs 10.1%, p < 0.001).
      alpha-, beta-, gamma-, and delta-tocopherols constituted 93-98% of total
      tocopherols and tocotrienols in seeds, and alpha-tocopherol alone constituted 76
      89% in berries. The total contents of tocopherols and tocotrienols varied within
      the ranges of 84-318 and 56-140 mg kg(-1) in seeds and whole berries,
      respectively. The seeds of ssp. mongolica were a better source of tocopherols and
      tocotrienols than those of ssp. sinensis (287 vs 122 mg kg(-1), p < 0.001). The
      compositional differences between the two subspecies should be considered when
      the berries are bred and exploited for nutritional purposes.

PMID- 11982434
TI  - Thermal processing enhances the nutritional value of tomatoes by increasing total
      antioxidant activity.
AB  - Processed fruits and vegetables have been long considered to have lower
      nutritional value than their fresh commodities due to the loss of vitamin C
      during processing. This research group found vitamin C in apples contributed <
      0.4% of total antioxidant activity, indicating most of the activity comes from
      the natural combination of phytochemicals. This suggests that processed fruits
      and vegetables may retain their antioxidant activity despite the loss of vitamin
      C. Here it is shown that thermal processing elevated total antioxidant activity
      and bioaccessible lycopene content in tomatoes and produced no significant
      changes in the total phenolics and total flavonoids content, although loss of
      vitamin C was observed. The raw tomato had 0.76 +/- 0.03 micromol of vitamin C/g
      of tomato. After 2, 15, and 30 min of heating at 88 degrees C, the vitamin C
      content significantly dropped to 0.68 +/- 0.02, 0.64 +/- 0.01, and 0.54 +/- 0.02
      micromol of vitamin C/g of tomato, respectively (p < 0.01). The raw tomato had
      2.01 +/- 0.04 mg of trans-lycopene/g of tomato. After 2, 15, and 30 min of
      heating at 88 degrees C, the trans-lycopene content had increased to 3.11+/-
      0.04, 5.45 +/- 0.02, and 5.32 +/- 0.05 mg of trans-lycopene/g of tomato (p <
      0.01). The antioxidant activity of raw tomatoes was 4.13 +/- 0.36 micromol of
      vitamin C equiv/g of tomato. With heat treatment at 88 degrees C for 2, 15, and
      30 min, the total antioxidant activity significantly increased to 5.29 +/- 0.26,
      5.53 +/- 0.24, and 6.70 +/- 0.25 micromol of vitamin C equiv/g of tomato,
      respectively (p < 0.01). There were no significant changes in either total
      phenolics or total flavonoids. These findings indicate thermal processing
      enhanced the nutritional value of tomatoes by increasing the bioaccessible
      lycopene content and total antioxidant activity and are against the notion that
      processed fruits and vegetables have lower nutritional value than fresh produce.
      This information may have a significant impact on consumers' food selection by
      increasing their consumption of fruits and vegetables to reduce the risks of
      chronic diseases.

PMID- 11982435
TI  - Phenolic compounds and related enzymes are not rate-limiting in browning
      development of fresh-cut potatoes.
AB  - The effect of minimal processing on polyphenol oxidase (PPO), peroxidase (POD),
      phenylalanine ammonia-lyase (PAL), and phenolic compounds was studied in five
      potato cultivars (Agria, Cara, Liseta, Monalisa, and Spunta). Minimal processing
      caused an overall increase in PPO, POD, and PAL activities. The isoform pattern
      of PPO was the same for all of the cultivars before and after processing. No
      latent PPO was detected. The isoperoxidase pattern was approximately the same
      among cultivars. An increase in POD activity was related to the specific
      induction of an acidic isoperoxidase. PAL showed an induction pattern
      characterized by the presence of a maximum peak of activity after 4 days of
      processing for all of the cultivars. The sequence of browning susceptibility of
      potato cultivars was as follows: Monalisa > Spunta > Liseta > Cara > Agria.
      Browning development was only partially correlated to PAL activity (only during
      the first 4 days after wounding). However, this correlation could not explain the
      above sequence of browning susceptibility. Minimal processing caused an increase
      of chlorogenic acid, whereas tyrosine content remained unchanged. In summary, no
      significant correlation was found between either rate or degree of browning and
      any other biochemical and physiological attribute investigated (PPO, POD,
      hydrogen peroxide, ascorbic acid content, and initial phenolics content as well
      as total and individual phenolics accumulation).

PMID- 11982436
TI  - Near-infrared analysis of soluble and insoluble dietary fiber fractions of cereal
      food products.
AB  - The use of near-infrared (NIR) reflectance spectroscopy for the rapid and
      accurate measurement of soluble and insoluble dietary fiber was explored in a
      diverse group of cereal products. Ground samples were analyzed for soluble and
      insoluble dietary fiber (AOAC Method 991.43) and scanned (NIRSystems 6500
      monochromator) to obtain NIR spectra. Modified PLS models were developed to
      predict insoluble and soluble dietary fiber using data sets expanded to include
      products with high fat and high sugar contents. The models predicted insoluble
      dietary fiber accurately with an SECV of 1.54% and an R(2) of 0.98 (AOAC
      determined range of 0-48.77%) and soluble dietary fiber less accurately with an
      SECV of 1.15% and an R(2) of 0.82 (AOAC determined range of 0-13.84%). Prediction
      of independent validation samples by the soluble fiber model resulted in a bias
      that may be related to the way the reference method treats samples with different
      soluble fiber constituents. The insoluble fiber model can be used to rapidly
      monitor insoluble dietary fiber in cereal products for nutrition labeling.

PMID- 11982437
TI  - Evaluation of the nutritional characteristics of a finger millet based
      complementary food.
AB  - Finger millet (Eleusine coracana), kidney beans (Phaseolus vulgaris), peanuts
      (Arachis hypogoea), and mango (Mangifera indica) were processed separately and
      then combined, on the basis of their amino acid scores and energy content, into a
      complementary food for children of weaning age. The finger millet and kidney
      beans were processed by germination, autoclaving, and lactic acid fermentation. A
      mixture containing, on a dry matter basis, 65.2, 19.1, 8.0, and 7.7% of the
      processed finger millet, kidney beans, peanuts, and mango, respectively, gave a
      composite protein with an in vitro protein digestibility of 90.2% and an amino
      acid chemical score of 0.84. This mixture had an energy density of 16.3 kJ.g(-1)
      of dry matter and a decreased antinutrient content and showed a measurable
      improvement in the in vitro extractability for calcium, iron, and zinc. A 33%
      (w/v) pap made from a mix of the processed ingredients had an energy density of
      5.4 kJ.g(-1) of pap, which is sufficient to meet the energy requirements of well
      nourished children of 6-24 months of age at three servings a day and at the FAO
      average breast-feeding frequency.

PMID- 11982438
TI  - Sulfated ferulic acid is the main in vivo metabolite found after short-term
      ingestion of free ferulic acid in rats.
AB  - The bioavailability of ferulic acid (FA; 3-methoxy-4-hydroxycinnamic acid) and
      its metabolites was investigated in rat plasma and urine after an oral short-term
      ingestion of 5.15 mg/kg of FA. Free FA, glucuronoconjugates, and sulfoconjugates
      were quickly detected in plasma with a peak of concentration found 30 min after
      ingestion. Sulfoconjugates were the main derivates ( approximately 50%). In
      urine, the cumulative excretion of total metabolites reached a plateau 1.5 h
      after ingestion, and approximately 40% were excreted by this way. Free FA
      recovered in urine represented only 4.9 +/-1.5% of the native FA consumed by
      rats. Glucuronoconjugates and sulfoconjugates represented 0.5 +/- 0.3 and 32.7 +/
      7.3%, respectively. These results suggested that a part of FA incorporated in
      the diet was quickly absorbed and largely metabolized in sulfoconjugates before
      excretion in urine.

PMID- 11982439
TI  - Food safety and amino acid balance in processed cassava "Cossettes".
AB  - Processed cassava (Manihot esculenta Crantz) roots provide more than 60% of the
      daily energy intake for the population of the Democratic Republic of Congo.
      Insufficiently processed cassava roots in a diet deficient in sulfur amino acid
      have been reported to cause the irreversible paralytic disease konzo, afflicting
      thousands of women and children in the remote rural areas of Bandundu Province.
      "Cossettes" (processed cassava roots) purchased in several markets of Kinshasa
      were analyzed for their content of cyanogens, free amino acids, and total protein
      amino acids. Residual cyanogen levels were below the safe limit recommended by
      the codex FAO/WHO for cassava flour (10 mg kg(-1)). The amino acid score was
      evaluated. Lysine and leucine were the limiting amino acids. Methionine content
      was very low and contributed about 13% of the total sulfur amino acids. Dietary
      requirements for sulfur amino acids need to be adjusted for the loss caused by
      cyanogen detoxification.

PMID- 11982440
TI  - Antioxidant capacity of honeys from various floral sources based on the
      determination of oxygen radical absorbance capacity and inhibition of in vitro
      lipoprotein oxidation in human serum samples.
AB  - Honeys from seven different floral sources were analyzed for in vitro antioxidant
      capacity and total phenolic content. Antioxidant capacity was measured by the
      oxygen radical absorbance capacity (ORAC) assay and by monitoring the formation
      of conjugated dienes as an index of the inhibition of copper-catalyzed serum
      lipoprotein oxidation. ORAC values ranged from 3.1 to 16.3 micromol Trolox
      equivalent/g honey. The darkest colored honeys, such as buckwheat honey, had the
      highest ORAC values. A linear correlation was observed between phenolic content
      and ORAC activity of the investigated honeys (p < 0.0001, R (2) = 0.9497). The
      relationship between the ORAC activity and inhibition of lipoprotein oxidation by
      the honeys yielded a correlation coefficient of 0.6653 (p = 0.0136). This work
      shows that honey may be used as a healthy alternative to sugar in many products
      and thereby serve as a source of dietary antioxidants.

PMID- 11982441
TI  - Gossypol and gossypolone enantiomers in tissues of rainbow trout fed low and high
      levels of dietary cottonseed meal.
AB  - Gossypol is an antifertilizing agent in males and females. However, gossypol and
      its metabolite, gossypolone, have also gained interest because of their
      anticarcinogenic activities. This paper examines for the first time both
      enantiomers of tissue gossypol and gossypolone in mature rainbow trout fed two
      diets containing low (15%) and high (60%) levels of cottonseed meal (CM) for 9
      months. The gossypol concentration was highest in liver followed by kidney,
      intestine, testis, blood plasma, stomach, and muscle. Gossypol was detected in
      muscles of fish fed low- and high-CM diets (0.31 +/- 0.03 and 1.95 +/- 0.59
      microg of total gossypol/g, wet basis, respectively). The (+)-gossypol enantiomer
      was predominantly retained in all tissues. The ratio of (-)- to total gossypol
      ranged from 30 to 44% in fish fed the high-CM diet and from 23 to 30% in fish fed
      the low-CM diet except for muscle tissue (44%). Higher gossypolone concentrations
      were found in intestine than in liver. Gossypolone, however, was not detected in
      blood plasma, muscle, and testis of fish fed the low-CM diet. The ratio of
      gossypolone to gossypol was highest in muscle (1.75), followed by intestine
      (1.59), stomach (1.50), kidney (0.43), liver (0.34), testis (0.28), and blood
      plasma (0.27). This study indicated that the retention of the (-)-gossypol
      enantiomer is dependent on dietary concentrations and that the oxidative
      conversion of gossypol to gossypolone occurs more actively in the digestive tract
      and muscle than in other tissues in rainbow trout.

PMID- 11982442
TI  - Rapid, non-destructive selection of peanuts for high aflatoxin content by soaking
      and tandem mass spectrometry.
AB  - Peanut lots are subject to aflatoxin levels high enough to cause concern to
      health agencies and trade channels. A possible solution would be to mechanically
      sort out high aflatoxin nuts from the process stream. Only highly contaminated
      nuts would need to be removed. However, there exists at present no sorting
      mechanism which meets commercial needs of adequate reduction and product
      preservation. To build such a sorter requires knowledge of the properties that
      can be used for sorting. The first step in the design is to select on the order
      of one hundred undamaged contaminated nuts which can be compared with
      noncontaminated ones. Because contaminated nuts are rare, a very large number of
      nuts needs to be examined nondestructively. We present a method to rapidly carry
      out such a selection. The method is based on dipping nuts into extraction fluid
      and examining the resulting fluid by tandem MS without preliminary cleanup. This
      method has been applied to examine over 65,000 nuts, yielding approximately 120
      nuts, each containing more than 250-43000 ng/g aflatoxin (depending on process
      stream).

PMID- 11982443
TI  - Mycotoxin production by Fusarium avenaceum strains isolated from Norwegian grain
      and the cytotoxicity of rice culture extracts to porcine kidney epithelial cells.
AB  - The secondary metabolites of 24 isolates of Fusarium avenaceum from Norwegian
      cereals and grown on rice have been characterized. Moniliformin (MON), enniatins
      (ENNs), and beauvericin (BEA) were analyzed by high-performance liquid
      chromatography. Porcine kidney epithelial cells (PK15, American Type Culture
      Collection) were used to study the cytotoxicity of MON in the extracts. The
      following metabolites were produced by all isolates, ranked by concentration in
      rice cultures: ENN-B, MON, ENN-B1, and ENN-A. BEA was produced by eight isolates.
      The productions of BEA and ENN-A were significantly correlated, as was the case
      with ENN-B and ENN-B1. MON production was correlated neither to any of the other
      toxins nor to toxicity.

PMID- 11982444
TI  - Probing brain reward system function in major depressive disorder: altered
      response to dextroamphetamine.
AB  - BACKGROUND: The state of the brain reward system in major depressive disorder was
      assessed with dextroamphetamine, which probes the release of dopamine within the
      mesocorticolimbic system, a major component of the brain reward system, and
      produces measurable behavioral changes, including rewarding effects (eg,
      euphoria). We hypothesized that depressed individuals would exhibit an altered
      response to dextroamphetamine due to an underlying brain reward system
      dysfunction reflected by anhedonic symptoms. METHODS: In a double-blind, placebo
      controlled, randomized, parallel study, the behavioral and physiological effects
      of a single 30-mg dose of oral dextroamphetamine sulfate were measured. Forty
      patients with a diagnosis of DSM-IV major depressive disorder who were not taking
      antidepressant medications (22 assigned to dextroamphetamine and 18 to placebo)
      were compared with 36 control subjects (18 assigned to dextroamphetamine and 18
      to placebo) using validated self-report drug effect measurement tools (eg, the
      Addiction Research Center Inventory), heart rate, and blood pressure. RESULTS:
      Multiple regression analysis showed that severity of depression as measured by
      the Hamilton Rating Scale for Depression correlated highly with the rewarding
      effects of dextroamphetamine in the depressed group (model R(2) = 0.63;
      interaction P =.04). A subsequent analysis categorizing the depressed group into
      patients with severe symptoms (Hamilton score >23) and those with moderate
      symptoms revealed a significant interaction between drug and depression (P =.02).
      Patients with severe symptoms reported rewarding effects 3.4-fold greater than
      controls. CONCLUSIONS: The results suggest the presence of a hypersensitive
      response is present in the brain reward system of depressed patients, which may
      reflect a hypofunctional state and may provide a novel pathophysiologic and
      therapeutic target for future studies.

PMID- 11982445
TI  - Disruption of neural systems of visual attention in schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia show attention deficits. The frontal P2a
      and posterior N2b event-related potential components are early indices of
      activity in neural systems supporting attention and they are reduced in
      schizophrenia in auditory tasks. However, the auditory P300 is reduced as well.
      Thus, the P2a and N2b reductions may simply reflect a general event-related
      potential amplitude reduction. The visual P300, however, is often spared in
      schizophrenia. If neural systems supporting attention are specifically disrupted
      in schizophrenia, the attention-sensitive P2a and N2b should be differentially
      reduced in patients, compared with the P300, in a visual attention task. METHODS:
      We analyzed 64-channel event-related potentials from 14 schizophrenic patients
      and 14 control subjects in a visual object-spatial attention task. We examined
      the amplitude of the P2a, N2b, and P300 components in the target minus standard
      difference wave to see if there was a differential reduction of the P2a and N2b
      compared with the P300. RESULTS: Both the P2a and N2b waveforms were reduced in
      the patient group (81% [control mean, 1.99 microV; patient mean, 0.38 microV] and
      95% [control mean, 0.55 microV; patient mean, 0.03 microV], respectively) while
      the P300 was not reduced. Measured at the peak of the frontal P2a, the N2b was
      larger dorsally in the spatial task and larger ventrally in the object task in
      the control group. CONCLUSIONS: The spatial distribution of the P2a and N2b was
      consistent with activity in the prefrontal cortex and modality-specific posterior
      cortex, respectively. The differential reduction of the P2a and N2b waveforms
      supports the hypothesis of specific disruption in neural systems of visual
      attention in schizophrenia.

PMID- 11982446
TI  - Common changes in cerebral blood flow in patients with social phobia treated with
      citalopram or cognitive-behavioral therapy.
AB  - BACKGROUND: Neurofunctional changes underlying effective antianxiety treatments
      are incompletely characterized. This study explored the effects of citalopram and
      cognitive-behavioral therapy on regional cerebral blood flow (rCBF) in social
      phobia. METHODS: By means of positron emission tomography with oxygen 15-labeled
      water, rCBF was assessed in 18 previously untreated patients with social phobia
      during an anxiogenic public speaking task. Patients were matched for sex, age,
      and phobia severity, based on social anxiety questionnaire data, and randomized
      to citalopram medication, cognitive-behavioral group therapy, or a waiting-list
      control group. Scans were repeated after 9 weeks of treatment or waiting time.
      Outcome was assessed by subjective and psychophysiological state anxiety measures
      and self-report questionnaires. Questions were readministered after 1 year.
      RESULTS: Symptoms improved significantly and roughly equally with citalopram and
      cognitive-behavioral therapy, whereas the waiting-list group remained unchanged.
      Four patients in each treated group and 1 waiting-list patient were classified as
      responders. Within both treated groups, and in responders regardless of treatment
      approach, improvement was accompanied by a decreased rCBF-response to public
      speaking bilaterally in the amygdala, hippocampus, and the periamygdaloid,
      rhinal, and parahippocampal cortices. Between-group comparisons confirmed that
      rCBF in these regions decreased significantly more in treated groups than control
      subjects, and in responders than nonresponders, particularly in the right
      hemisphere. The degree of amygdalar-limbic attenuation was associated with
      clinical improvement a year later. CONCLUSIONS: Common sites of action for
      citalopram and cognitive-behavioral treatment of social anxiety were observed in
      the amygdala, hippocampus, and neighboring cortical areas, ie, brain regions
      subserving bodily defense reactions to threat.

PMID- 11982447
TI  - Personality disorders and time to remission in generalized anxiety disorder,
      social phobia, and panic disorder.
AB  - BACKGROUND: This investigation assessed the effect of personality disorders
      (PersDs) on time to remission in patients with generalized anxiety disorder,
      social phobia, or panic disorder. METHODS: Selected Axis I and II predictors of
      time to remission during 5 years of follow-up were assessed in 514 patients with
      1 or more of these anxiety disorders who participated in the Harvard/Brown
      Anxiety Research Program, a multisite, prospective, longitudinal, naturalistic
      study. RESULTS: The presence of a PersD predicted a 30% lower likelihood of
      generalized anxiety disorder remission, a 39% lower likelihood of social phobia
      remission, and no difference in likelihood of panic disorder remission. More
      specifically, a lower likelihood of remission from generalized anxiety disorder
      was predicted by the presence of avoidant PersD (34% lower) and dependent PersD
      (14% lower). The presence of avoidant PersD predicted a 41% lower likelihood of
      social phobia remission. The presence of major depressive disorder did not
      account for these findings. CONCLUSIONS: Our findings provide new data on the
      pernicious effect of PersDs on the course of generalized anxiety disorder and
      social phobia but not panic disorder, suggesting that PersDs have a differential
      effect on the outcome of anxiety disorders.

PMID- 11982448
TI  - A double-blind, placebo-controlled dose-response comparison of intramuscular
      olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.
AB  - BACKGROUND: An intramuscular (IM) formulation of olanzapine has been developed
      because there are no rapid-acting IM atypical antipsychotic drugs currently
      available in the United States for treating acute agitation in patients with
      schizophrenia. METHODS: Recently hospitalized acutely agitated patients with
      schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of
      olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within
      24 hours. A dose-response relationship for IM olanzapine in the reduction of
      agitation was assessed by measuring the reduction in Positive and Negative
      Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first
      injection. Safety was assessed by recording adverse events and with
      extrapyramidal symptom scales and electrocardiograms at 24 hours after the first
      injection. RESULTS: Olanzapine exhibited a dose-response relationship for
      reduction in agitation (F(1,179)= 14.4; P<.001). Mean PANSS-EC reductions 2 hours
      after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = 
      8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P =.01 vs
      olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with
      haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater
      reduction in agitation than placebo 30 minutes after the first injection. There
      were no differences between treatment groups for hypotension, the most frequently
      reported adverse event, or for clinically relevant changes in the QTc interval.
      There was a greater incidence of treatment-emergent parkinsonism during treatment
      with IM haloperidol (16.7%) than with 2.5 (P =.03), 5.0 (P =.03), or 7.5 mg (P
      =.01) of IM olanzapine (0%) or with placebo (0%) (P =.01). CONCLUSIONS:
      Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a
      dose-response relationship in the rapid treatment of acute agitation in patients
      with schizophrenia and demonstrates a favorable safety profile.

PMID- 11982449
TI  - Evidence for early-childhood, pan-developmental impairment specific to
      schizophreniform disorder: results from a longitudinal birth cohort.
AB  - BACKGROUND: Childhood developmental abnormalities have been previously described
      in schizophrenia. It is not known, however, whether childhood developmental
      impairment is specific to schizophrenia or is merely a marker for a range of
      psychiatric outcomes. METHODS: A 1-year birth cohort (1972-1973) of 1037 children
      enrolled in the Dunedin Multidisciplinary Health and Development Study was
      assessed at biennial intervals between ages 3 and 11 years on emotional,
      behavioral, and interpersonal problems, motor and language development, and
      intelligence. At age 11 years, children were asked about psychotic symptoms. At
      age 26 years, DSM-IV diagnoses were made using the Diagnostic Interview Schedule.
      Study members having schizophreniform disorder (n = 36 [3.7%]) were compared with
      healthy controls and also with groups diagnosed as having mania (n = 20 [2%]) and
      nonpsychotic anxiety or depression disorders (n = 278 [28.5%]) on childhood
      variables. RESULTS: Emotional problems and interpersonal difficulties were noted
      in children who later fulfilled diagnostic criteria for any of the adult
      psychiatric outcomes assessed. However, significant impairments in neuromotor,
      receptive language, and cognitive development were additionally present only
      among children later diagnosed as having schizophreniform disorder. Developmental
      impairments also predicted self-reported psychotic symptoms at age 11 years.
      These impairments were independent of the effects of socioeconomic, obstetric,
      and maternal factors. CONCLUSIONS: The results provide evidence for an early
      childhood, persistent, pan-developmental impairment that is specifically
      associated with schizophreniform disorder and that predicts psychotic symptoms in
      childhood and adulthood.

PMID- 11982450
TI  - Minor physical anomalies and quantitative measures of the head and face in
      patients with psychosis.
AB  - BACKGROUND: The aim of this study was to examine minor physical anomalies and
      quantitative measures of the head and face in patients with psychosis vs healthy
      controls. METHODS: Based on a comprehensive prevalence study of psychosis, we
      recruited 310 individuals with psychosis and 303 controls. From this sample, we
      matched 180 case-control pairs for age and sex. Individual minor physical
      anomalies and quantitative measures related to head size and facial height and
      depth were compared within the matched pairs. Based on all subjects, we examined
      the specificity of the findings by comparing craniofacial summary scores in
      patients with nonaffective or affective psychosis and controls. RESULTS: The odds
      of having a psychotic disorder were increased in those with wider skull bases
      (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.02-1.17), smaller lower
      facial heights (glabella to subnasal) (OR, 0.57; 95% CI, 0.44-0.75), protruding
      ears (OR, 1.72; 95% CI, 1.05-2.82), and shorter (OR, 2.29; 95% CI, 1.37-3.82) and
      wider (OR, 2.28; 95% CI, 1.43-3.65) palates. Compared with controls, those with
      psychotic disorder had skulls that were more brachycephalic. These differences
      were found to distinguish patients with nonaffective and affective psychoses from
      controls. CONCLUSIONS: Several of the features that differentiate patients from
      controls relate to the development of the neuro-basicranial complex and the
      adjacent temporal and frontal lobes. Future research should examine both the
      temporal lobe and the middle cranial fossa to reconcile our anthropomorphic
      findings and the literature showing smaller temporal lobes in patients with
      schizophrenia. Closer attention to the skull base may provide clues to the nature
      and timing of altered brain development in patients with psychosis.

PMID- 11982451
TI  - Can sublingual testosterone increase subjective and physiological measures of
      laboratory-induced sexual arousal?

PMID- 11982452
TI  - Is NMDA receptor hypofunction in schizophrenia associated with a primary
      hyperglutamatergic state?

PMID- 11982454
TI  - Disconnected networks during auditory hallucinations and dreams: a topological
      problem for neuroimaging?

PMID- 11982456
TI  - Pharmacotherapy of paraphilias with luteinizing hormone-releasing hormone
      agonists.

PMID- 11982458
TI  - Limitations of the Bonn Scale for the Assessment of Basic Symptoms as a screening
      measure.

PMID- 11982460
TI  - Antiobsessional effect of risperidone add-on treatment in serotonin reuptake
      inhibitor-refractory obsessive-compulsive disorder may be dose-dependent.

PMID- 11982462
TI  - Workforce and lifestyle issues in general surgery training and practice.

PMID- 11982463
TI  - Prophylactic and therapeutic inferior vena cava filters to prevent pulmonary
      emboli in trauma patients.
AB  - HYPOTHESIS: Insertion of inferior vena cava filters (IVCFs) can prophylactically
      reduce pulmonary embolism (PE) in trauma patients. DESIGN: Retrospective review.
      SETTING: Urban, level I trauma center. PATIENTS: Two hundred blunt trauma
      patients undergoing IVCF placement. INTERVENTIONS: In 122 patients who had
      already been diagnosed as having deep vein thrombosis (DVT) (112 patients) and/or
      PE (22 patients), the insertion of the IVCF was considered "therapeutic." In 78
      patients who had no evidence of DVT or PE but who were considered to be at high
      risk for a PE, the IVCF was considered "prophylactic." MAIN OUTCOME MEASURES:
      Incidence of PE and related mortality and morbidity in therapeutic vs
      prophylactic IVCFs. RESULTS: The number of prophylactic IVCFs inserted increased
      significantly from only 4% (3/68 cases) from 1991 through 1996, up to 57% (75/132
      cases) from 1997 to June 2001. Although the mean +/- SD age (51 +/- 20 years vs
      41 +/- 15 years; P<.001) was higher in the therapeutic group, there was no
      difference in the mean +/- SD Injury Severity Scores (20 +/- 12 vs 21 +/- 11).
      Therapeutic filters were placed much later after injury (mean +/- SD time, 11 +/-
      7 vs 3 +/- 2 days; P<.001). The mortality rate was 11% (13/122 patients) in
      patients having a therapeutic IVCF, as compared with only 3% (2/78 patients) in
      those placed prophylactically (P =.07). None of the patients who had placement of
      a prophylactic IVCF developed subsequent PE. The incidence of PE decreased in all
      blunt trauma patients from 0.29% before 1997 to 0.15% after January 1, 1997, when
      57% of the IVCF inserted were prophylactic (P =.06). CONCLUSIONS: Prophylactic
      IVCFs should be inserted within 48 hours of injury in specific trauma patients at
      high risk for PE and with contraindications to anticoagulation.

PMID- 11982464
TI  - Learning laparoscopic donor nephrectomy safely: a report on 100 cases.
AB  - HYPOTHESIS: There is concern that learning laparoscopic live donor nephrectomy
      (LLDN) is associated with increased morbidity. We propose that with a team
      approach LLDN can be learned safely, without increased donor morbidity or graft
      failure, even during the early portion of a learning curve. DESIGN: Case series
      with cohort comparison. SETTING: Tertiary referral center. PATIENTS: The
      laparoscopic group consisted of 100 donors and 100 recipients; the open group, 50
      donors and 50 recipients. INTERVENTIONS: A team approach that combines
      laparoscopic and urologic expertise was used to perform 100 cases of LLDN. MAIN
      OUTCOME MEASURES: Donor morbidity and graft function in the laparoscopic group
      were compared with those in the open group. RESULTS: Laparoscopic live donor
      nephrectomy was completed in 99 patients. One patient required conversion to open
      donor nephrectomy because of intraoperative hemorrhage. Minor complications
      occurred in 6 laparoscopic group donors (6%) and 3 open group donors (6%).
      Laparoscopic and open group donors were of similar age. Operative times were
      longer for laparoscopic group donors (231 vs 209 minutes). Mean hospital stay was
      shorter for laparoscopic group donors (3.3 vs 4.7 days). Graft function was
      comparable between the laparoscopic and open groups, with equivalent
      postoperative creatinine levels. Graft survival was comparable. Recipient
      ureteral complications occurred with less frequency (2% vs 6%) in the
      laparoscopic group. CONCLUSIONS: By forming an operative team that combines
      expertise in laparoscopy with expertise in live donor nephrectomy, surgeons can
      learn LLDN safely. Adoption of the techniques developed by those who pioneered
      the procedure can further minimize the morbidity associated with a learning
      curve.

PMID- 11982465
TI  - Severe trauma is not an excuse for prolonged antibiotic prophylaxis.
AB  - HYPOTHESIS: For critically injured patients, a limited course of antibiotics is
      as effective as a prolonged course in preventing sepsis and organ failures.
      DESIGN: Prospective nonrandomized study. SETTING: Surgical intensive care unit
      (SICU) of an academic hospital with a level I trauma center. PATIENTS: A
      population of 250 trauma patients who required an operation and SICU stay of 3
      days or more received antibiotic prophylaxis by 1 antibiotic for 24 hours (SHORT
      group, n = 133) or 1 or more antibiotics for more than 24 hours (LONG group, n =
      117). MAIN OUTCOME MEASURES: Twenty-two outcome variables, including 9
      conventional outcomes (eg, sepsis, septic shock, and organ failure) and 13
      objective outcomes (days with temperature >38.5 degrees C, days with white blood
      cell count >14.0 x10(3)/microL, positive cultures, cultures with antibiotic
      resistant bacteria, SICU and hospital stay, and death). RESULTS: The LONG group
      included more patients with orthopedic injuries (60 patients [51%] vs 52 [39%], P
      =.05) and orthopedic operations (47 patients [40%] vs 30 [23%], P =.003) than did
      the SHORT group. No other difference was identified in compared characteristics
      between the 2 groups. There was no difference in any of the examined outcomes
      except for a higher incidence of resistant infections in the LONG group compared
      with the SHORT group (59 patients [50%] vs 47 [35%], P =.02). Patients with
      resistant infections stayed in the hospital longer (mean +/- SD, 33 +/- 18 vs 15
      +/- 11 days, P<.001) and had a higher mortality rate (13% vs 1%, P<.001) compared
      with patients without resistant infections. Prolonged prophylaxis by multiple
      antibiotics was an independent risk factor of resistant infection (odds ratio,
      2.13, 95% confidence interval, 1.22-3.74; P =.008). CONCLUSIONS: The prophylactic
      administration of more than 1 antibiotic for more than 24 hours following severe
      trauma does not offer additional protection against sepsis, organ failure, and
      death, but increases the probability of antibiotic-resistant infections.

PMID- 11982466
TI  - Interval sentinel lymph nodes in melanoma.
AB  - HYPOTHESIS: For patients with melanoma, interval or in-transit sentinel lymph
      nodes (SLNs) have the same risk for nodal metastasis as SLN in traditional (ie,
      cervical, axillary, and inguinal) nodal basins. DESIGN: Prospective clinical
      trial. SETTING: Multicenter study. PATIENTS: Eligible patients were aged 18 to 70
      years with melanomas of at least 1.0-mm Breslow thickness and nodes with
      clinically negative findings. INTERVENTION: Sentinel lymph node biopsy was guided
      by preoperative lymphoscintigraphy to identify all SLNs. MAIN OUTCOME MEASURES:
      We evaluated interval nodal sites, including epitrochlear, popliteal, and
      subcutaneous or intramuscular nodes outside of traditional basins, for the
      presence of metastases. RESULTS: The SLNs were identified in 2332 nodal basins
      from 2000 patients. In 62 patients (3.1%), interval SLNs were identified. We
      found SLN metastases in 442 (19.5%) of 2270 conventional nodal basins and 13
      (21.0%) of 62 interval sites. In 11 (84.6%) of the 13 cases in which we found an
      interval node that was positive for metastatic disease, it was the only site of
      nodal metastasis. CONCLUSIONS: Although interval SLNs are identified
      infrequently, they contain metastatic disease at nearly the same frequency as
      SLNs in cervical, axillary, and inguinal nodal basins. Positive interval SLNs are
      likely to be the only site of nodal metastasis. Therefore, detailed preoperative
      lymphoscintigraphy and meticulous intraoperative search for interval nodes should
      be performed.

PMID- 11982467
TI  - Disparate outcomes in patients with colorectal cancer: effect of race on long
      term survival.
AB  - BACKGROUND: Increasing evidence suggests significant disparity in colorectal
      cancer outcomes between black and white patients. Contributing factors may
      include advanced tumor stage at diagnosis, differences in treatment, more
      aggressive tumor biology, access to care, and patient comorbidity. HYPOTHESIS:
      Disparities in colorectal cancer outcomes exist despite similar objective
      measures of treatment. DESIGN AND SETTING: Ten-year retrospective review of all
      patients with colorectal cancer using tumor registries at a city hospital (n =
      83) and a university medical center (n = 585) in the same city. We assessed stage
      at diagnosis; curative surgical resection; use of adjuvant treatment; overall,
      disease-free, and stage-specific survival; and socioeconomic status. Patients
      with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in
      stage and treatments were compared using the chi(2) test, and median survival
      rates were compared using log-rank tests. RESULTS: Significantly more black
      patients were treated at the city hospital (53.0%) vs the university medical
      center (10.6%) (P<.001). No differences were identified in stage distribution or
      treatments received between hospitals or between black and white patients.
      Significantly worse survival was noted among patients treated at the city
      hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both
      institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs
      5.7 years; P<.001 for both). Disease-free survival rates showed similar
      significant reductions for black patients at both institutions. There was no
      association between survival and socioeconomic status at either institution.
      CONCLUSION: The marked reductions in overall and disease-free survival for black
      patients with colorectal cancer do not seem to be related to variation in
      treatment but may be due to biologic factors or non-cancer-related health
      conditions.

PMID- 11982469
TI  - Pancreas-sparing duodenectomy for duodenal polyposis.
AB  - HYPOTHESIS: Pancreas-sparing duodenectomy (PSD) is a safe and effective operative
      procedure for patients with nonmalignant duodenal polyps. DESIGN: Retrospective
      analysis of outcomes in patients undergoing PSD. SETTING: A tertiary referral
      center. PATIENTS: All patients undergoing PSD at the Mayo Clinic, Rochester,
      Minn. Indications were the presence of numerous duodenal polyps or large,
      solitary, adenomatous polyps not amenable to endoscopic resection. Dysplasia
      without frank malignancy was demonstrated in all patients by endoscopic biopsy
      specimens. Follow-up was complete in all patients. MAIN OUTCOME MEASURES:
      Operative feasibility, short- and long-term complications, quality of life, and
      survival. RESULTS: Five patients had diffuse polyposis (familial adenomatous
      polyposis) and 3 had very large periampullary villous adenomas. The mean age of
      the patients was 54 years (female-male ratio, 3:1). Colectomy preceded PSD in 5
      patients (familial adenomatous polyposis); 3 had previous transduodenal excision
      of adenomas, and 2 had previous resections of desmoid tumors. The mean operating
      room time was 370 minutes; blood loss, 340 mL; and the length of the hospital
      stay, 18 days. All specimens showed dysplasia (5 low grade, 3 high grade). There
      were 5 major complications--3 ampullary leaks that closed spontaneously with
      drainage, 1 intra-abdominal hemorrhage requiring a second exploratory surgical
      procedure, and 1 deep wound infection. The mean follow-up was 23 months. All
      patients experienced weight gain and good performance status. A second endoscopy
      (performed in 5 patients) demonstrated small polyps in the neoduodenum in 2
      patients and tiny anastomotic ulcers in 2 patients. For 1 patient, there were no
      abnormalities seen on the endoscopy. Two patients have since developed transient
      bouts of pancreatitis. CONCLUSIONS: Pancreas-sparing duodenectomy, although
      technically demanding, eliminates the need for pancreatic resection. Pancreas
      sparing duodenectomy is associated with good absorptive capacity, weight gain,
      and quality of life. Furthermore, it may reduce the risk of subsequent
      malignancy. Long-term surveillance, however, is still required. Pancreas-sparing
      duodenectomy is contraindicated in the setting of malignancy.

PMID- 11982470
TI  - Primary cancers of the small bowel: analysis of prognostic factors and results of
      surgical management.
AB  - HYPOTHESIS: This study was done to review the clinical presentation, surgical
      management, pathologic features, and prognostic factors for primary small-bowel
      cancers. DESIGN: Retrospective case series. SETTING: Tertiary care, university
      hospital. PATIENTS: One hundred twenty-nine patients were surgically treated
      between January 1, 1977, and December 31, 2000. There were 73 men and 56 women,
      with a median age of 55 years (age range, 19-82 years). Median follow-up was 36
      months. MAIN OUTCOME MEASURES: Presenting symptoms and signs, operations
      performed, and surgical pathologic features were analyzed and survival curves
      were generated. RESULTS: Clinical findings included abdominal pain (63%),
      vomiting (48%), weight loss (44%), and gastrointestinal tract bleeding (23%). The
      distribution of tumors by histological features was as follows: adenocarcinoma
      (33%), carcinoid tumor (29%), lymphoma (19%), and sarcoma (19%). Cumulative 5
      year survival rate was 37% in the adenocarcinoma group, 64% in the carcinoid
      tumor group, 29% in the lymphoma group, and 22% in the sarcoma group. Significant
      prognostic predictors of overall survival for the entire cohort and for each
      tumor subtype included complete resection and American Joint Committee on Cancer
      tumor stage (P<.05). Patient age, tumor location, histological grade, and use of
      chemotherapy and radiation therapy did not significantly influence survival.
      Curative resections were accomplished in 83 patients (64%) with a median survival
      of 37 months compared with 46 patients undergoing incomplete or palliative
      resections with a median survival of 10 months (P<.05). Adjacent organ resection
      was required in 18 (22%) of the 83 patients undergoing potentially curative
      resections. The median time to recurrence was 16 months. Twenty-one patients
      (16%) developed associated primary cancers. CONCLUSIONS: Aggressive surgical
      resection in an attempt to achieve complete tumor removal seems warranted.
      Despite complete resections, patients with high-stage tumors remain at risk for
      recurrence.

PMID- 11982471
TI  - Use of hepatitis B core antibody-positive donors in orthotopic liver
      transplantation.
AB  - HYPOTHESIS: Hepatic allografts from donors positive for antibody to hepatitis B
      core antigen (anti-HBc) frequently transmit hepatitis B virus (HBV) infection to
      recipients. Therefore, most transplantation centers will not use these organs for
      orthotopic liver transplantation (OLT). Although it is expensive and not always
      efficacious, hepatitis B immune globulin (HBIG) has been used routinely for
      indefinite periods to prevent HBV infection in liver allograft recipients. We
      assessed the effectiveness of long-term use of a nucleoside analog, lamivudine,
      in preventing HBV transmission by anti-HBc-positive allografts. DESIGN:
      Retrospective study. SETTING: A tertiary care center. PATIENTS: Twelve patients
      received hepatic allografts from anti-HBc-positive donors at Loyola University
      Medical Center, Chicago, between February 23, 1998, and March 13, 2001.
      INTERVENTION: All patients received 10 000 U/d of intravenous HBIG for 7 days. In
      addition, they received 300 mg/d of lamivudine in divided doses. Their liver
      biopsy specimens were tested for HBV DNA, hepatitis B surface antigen (HBsAg),
      and hepatitis B core antibody (HBcAb). Serum samples from the donor and recipient
      were tested for HBcAb, HBV DNA, and hepatitis B surface antibody (HBsAb). MAIN
      OUTCOME MEASURE: The incidence of HBV infection in recipients who received HBcAb
      positive donor livers and lamivudine prophylaxis. RESULTS: All recipients were
      anti-HBc negative before OLT. Five of the recipients had HBsAb titers greater
      than 150 U at the time of OLT. Three of the donor livers were HBV DNA positive
      and 2 were hepatitis B core antigen positive at the time of OLT. Donor serum was
      HBcAb positive in all 12 donors. None of the recipients have become infected with
      HBV with a follow-up of 2 to 38 months. CONCLUSION: Perioperative use of HBIG
      combined with long-term use of lamivudine can prevent HBV infection in recipients
      who receive hepatic allografts from HBcAb-positive donors.

PMID- 11982472
TI  - Standardized trauma resuscitation: female hearts respond better.
AB  - HYPOTHESIS: Women respond better to standardized shock resuscitation compared
      with similarly severely injured men. DESIGN: Severely injured patients who met
      specific criteria were resuscitated using a standardized protocol with no
      adjustment for gender. The resuscitation protocol was used to attain and to
      maintain an oxygen delivery index of 600 mL/min. m(2) or greater (DO(2)I > or =
      600) for the first 24 hours in the intensive care unit (ICU). Interventions,
      responses, and outcomes for the 2 cohorts were compared. Data were analyzed using
      analysis of variance, chi(2), and t tests; P<.05 was considered significant.
      SETTING: A 20-bed regional level I trauma center ICU. PATIENTS: Patients at high
      risk of postinjury multiple organ failure (major organ or vascular injury and/or
      skeletal fractures, initial arterial base deficit of 6 mEq/L or greater,
      requirement for 6 units or more of packed red blood cells in the first 12 hours
      after hospital admission, or age > or = 65 years with any 2 previous criteria).
      INTERVENTIONS: Pulmonary artery catheter, packed red blood cell transfusion,
      crystalloid fluid infusion, inotrope, and vasopressor support, as needed, in that
      sequence, to maintain DO(2)I > or = 600. MAIN OUTCOME MEASURES: Hemodynamic
      response to resuscitation, fluid, and packed red blood cell volume. RESULTS:
      During 2000, 58 patients (38 men, 20 women) met criteria and were resuscitated
      using our standardized protocol. Demographics and outcomes were similar for both
      cohorts. Requirements for and responses to standardized resuscitation were also
      similar, except for volume loading. The female cohort required less lactated
      Ringer solution volume (12 +/- 1 vs 8 +/- 2 L, P<.05), required less Starling
      curve intervention (42% vs 15%, P<.05), and maintained the DO(2)I goal with
      average pulmonary capillary wedge pressure that was less than that of the male
      cohort. CONCLUSION: Review of prospective data from standardized shock
      resuscitation for female and male cohorts demonstrates that women respond better
      to standardized resuscitation compared with similarly severely injured men.

PMID- 11982473
TI  - Blunt lower-extremity trauma and popliteal artery injuries: revisiting the case
      for selective arteriography.
AB  - HYPOTHESIS: Abandoning mandatory angiography in patients with blunt lower
      extremity trauma and normal neurovascular examination results does not affect
      limb salvage. DESIGN: Retrospective, nonrandomized cohort study. Mean follow-up
      (31 of 52 patients) of 9.5 months (range, 0-96 months). SETTING: Single
      institution, academic level I trauma center. PATIENTS: Medical records of
      patients presenting on an emergency basis with knee dislocation, distal femoral
      fractures, or proximal tibial fractures during a 20-year period were reviewed.
      Fifty-three injuries occurred in 52 patients. Patients were predominantly male
      (81%) and young (mean age, 32.7 years). Mechanisms and side of extremity injury,
      coincident injuries, and neurovascular status on admission were recorded. Hard
      signs of arterial insufficiency or compartment syndrome were identified.
      INTERVENTIONS: Angiographic findings and operative and nonoperative interventions
      were recorded to identify whether angiographic data would alter therapy dictated
      by clinical findings alone. MAIN OUTCOME MEASURES: Limb salvage rate and
      necessity for vascular surgical intervention based on angiographic data in
      patients with normal neurovascular examination results. RESULTS: Multiorgan
      trauma occurred in 11 patients. Pulses were normal in 35, absent in 16, and
      diminished or identified by Doppler signal in 2. Arterial insufficiency or
      compartment syndrome was present in 29%. Twenty-seven patients (28 limbs)
      underwent angiography at the discretion of the attending surgeon. Of 13 abnormal
      arteriograms, 2 occurred in patients with normal pulses and 11 in patients with
      abnormal examination results. Thirteen of 36 patients with normal pulses
      underwent angiography; none had clinically significant arterial injuries that
      necessitated intervention. No vascular interventions were necessary in 23
      patients with normal pulses who did not undergo angiography (P<.001). Normal
      neurovascular status bore a 100% negative predictive value in determining the
      necessity of vascular intervention. CONCLUSIONS: Angiography is unnecessary in
      the routine evaluation of the patient with blunt lower-extremity trauma who
      presents with a normal neurovascular examination result and can be used
      selectively for patients with diminished pulses who lack associated indications
      for mandatory operative exploration.

PMID- 11982474
TI  - Circulating mediators and organ function in patients undergoing planned
      relaparotomy vs conventional surgical therapy in severe secondary peritonitis.
AB  - HYPOTHESIS: Planned relaparotomy (PRL) has been suggested to have detrimental
      effects on the systemic activation of inflammation mediators, thereby enhancing
      organ dysfunctions as assessed by clinical scores in secondary peritonitis.
      DESIGN: Prospective, nonrandomized control trial. SETTING: Intensive care units
      of an urban and a university teaching hospital. PATIENTS: Twenty-nine patients
      with secondary peritonitis. INTERVENTIONS: Of the 29 patients with comparable
      initial peritonitis conditions, 11 underwent PRL and 18 obtained primary
      abdominal closure. Blood samples were obtained preoperatively and at 2, 6, 8, 12,
      18, 24, 30, 36, 42, and 48 hours after the primary operation, then every 12th
      hour until day 5 and once daily until day 8. MAIN OUTCOME MEASURES:
      Quantification of circulating inflammation parameters (coagulation, acute-phase
      proteins, cytokine system, cell adhesion, opsonization) in correlation with Acute
      Physiology and Chronic Health Evaluation II, multiple organ failure, and Sepsis
      Related Organ Failure Assessment scores. RESULTS: Preoperatively, the patient
      groups did not differ in mean age, cause of peritonitis, or clinical scores. On
      average, 5.1 (SEM, +/- 0.7; range, 3-11) lavage treatments were performed in the
      PRL group, with 90% of the procedures executed during the first 6 days. The PRL
      treatment resulted in a significantly higher need of blood components and an
      increased inflammation mediator response, especially concerning coagulation
      factors, proinflammatory cytokines, adhesion molecules, and opsonic parameters.
      During PRL, clinical score systems showed higher values and a delayed decline
      compared with primary abdominal closure treatment. Incidence of multiorgan
      failure, mortality, and the mean intensive care unit hospitalization period were
      clearly more pronounced in the PRL group. CONCLUSION: In our pilot study,
      additional lavage treatment of secondary peritonitis resulted in an enhancement
      of systemic inflammatory mediator response (in particular interleukin 8), which
      may contribute to a further impairment of organ function.

PMID- 11982475
TI  - Antidiuretic hormone release during laparoscopic donor nephrectomy.
AB  - BACKGROUND: During laparoscopic procedures, increased intra-abdominal pressure
      may cause transient renal dysfunction due to impaired renal blood flow and
      induction of neurohormones. However, the relationship between antidiuretic
      hormone (ADH) secretion and increased intra-abdominal pressure is poorly
      understood. HYPOTHESIS: Laparoscopic donor nephrectomy (LDN) is associated with
      an increase in plasma ADH concentration, which influences renal function in both
      the donor and transplanted graft. OBJECTIVES: To evaluate plasma ADH levels
      during LDN and to correlate ADH levels with graft function. DESIGN AND
      INTERVENTIONS: In 30 patients who underwent LDN, plasma ADH levels were collected
      before insufflation, during surgery, after desufflation, and 24 hours after the
      procedure. In 6 patients who had open donor nephrectomy, blood samples were
      obtained as controls. Furthermore, graft function, operative characteristics, and
      clinical outcome were compared. SETTING: University hospital. RESULTS: In the LDN
      group, mean ADH levels during pneumoperitoneum and 30 minutes postinsufflation
      were significantly higher compared with preinsufflation values (P<.001). Twenty
      four hours after LDN, mean ADH levels had returned to normal values. There were
      no significant differences in ADH levels in the open donor nephrectomy group. No
      significant differences in either intraoperative diuresis, blood pressure
      readings, or postoperative graft function were documented among the 2 groups.
      CONCLUSIONS: In this study, LDN was associated with an increase in plasma ADH
      that appeared to be related to increased intra-abdominal pressure. We conclude
      that the increased ADH concentrations during LDN are not associated with
      clinically significant changes in either the kidney donor or the transplanted
      graft.

PMID- 11982477
TI  - Role of primary breast cancer characteristics in predicting positive sentinel
      lymph node biopsy results: a multivariate analysis.
AB  - HYPOTHESIS: Certain primary breast tumor characteristics can be used to predict
      positive sentinel lymph node biopsy (SLNB) results and thus determine which
      patients should undergo SLNB. DESIGN: Retrospective review of patients undergoing
      SLNB for invasive breast cancer from March 1, 1998, through March 31, 2001.
      SETTING: University-affiliated tertiary care hospital. PATIENTS: Two hundred
      fifty-seven consecutive patients undergoing successful SLNB. MAIN OUTCOME
      MEASURES: Correlation of patient age, tumor size, histological subtype, grade,
      lymphovascular invasion (LVI), host lymphoid reaction, border of neoplasm,
      characteristics of ductal carcinoma in situ, presence or absence of lobular
      carcinoma in situ, estrogen receptor, and her-2-neu oncogene status with positive
      SLNB results. Univariate and multivariate analyses were applied. Stepwise
      multiple logistic regression analysis identified variables predictive of positive
      SLNB results (P< or = .05). RESULTS: : Regression analysis identified tumor size
      and LVI as the only variables predictive of positive SLNB results. Results of
      SLNB were positive in 73 (28.4%) of 257 patients (T1a, 5/37 [13.5%]; T1b, 19/93
      [20.4%]; T1c, 37/103 [35.9%]; and T2, 12/24 [50.0%]). Although LVI did not
      correlate with tumor size, it was highly predictive of positive SLNB results by
      means of the following equation: 1/(1 + e(-z)), where z = 0.3079 + 1.3814 (LVI), 
      1.1869 (T1a), -0.3235 (T1b), or +0.5724 (T1c). CONCLUSIONS: Tumor size and LVI
      were the only variables independently predictive of positive SLNB results.
      Lymphovascular invasion was the strongest predictor. These data show a higher
      than expected incidence of positive SLNB for all tumor sizes, which may be
      explained by results of immunohistochemical analysis of sentinel lymph nodes, and
      which suggest that all patients with invasive breast cancer should be offered
      SLNB. Further studies with a larger cohort of patients are warranted.

PMID- 11982478
TI  - Complications in surgical patients.
AB  - HYPOTHESIS: Complications are common in hospitalized surgical patients. Provider
      error contributes to a significant proportion of these complications. DESIGN:
      Surgical patients were concurrently observed for the development of explicit
      complications. All complications were reviewed by the attending surgeon and other
      members of the service and evaluated for the severity of sequelae (major or
      minor) and for whether the complication resulted from medical error (avoidable)
      or not. SETTING: University teaching hospital with a level I trauma designation.
      PATIENTS: All inpatients (operative or nonoperative) from 4 different surgical
      services: general surgery, combined general surgery and trauma, vascular surgery,
      and cardiothoracic surgery. MAIN OUTCOME MEASURES: Total complication rate
      (number of complications divided by the number of patients) and the number of
      patients with complications. Complications were separated into those with major
      or minor sequelae and the proportion of each type that were due to medical error
      (avoidable). Rates of complications in a recent Institute of Medicine report were
      used as a criterion standard. RESULTS: The data for the respective groups
      (general surgery, vascular surgery, combined general surgery and trauma, and
      cardiothoracic surgery) are as follows. The number of patients was 1363, 978,
      914, and 1403; number of complications, 413, 409, 295, and 378; total
      complication rate, 30.3%, 42.4%, 32.3%, and 26.9%; minor complication rate,
      13.3%, 19.9%, 13.5%, and 13.0% (percentage of minor complications that were
      avoidable, 37.4%, 59.0%, 51.2%, and 49.5%); major complication rate, 16.2%,
      21.1%, 18.1%, and 12.9% (percentage of major complications that were avoidable,
      53.4%, 60.7%, 38.8%, and 38.7%); and mortality rate, 1.83%, 3.33%, 2.28%, and
      3.34% (percentage of mortality that was avoidable, 28.0%, 44.1%, 19.0%, and
      25.0%). CONCLUSIONS: Despite mortality rates that compare favorably with national
      benchmarks, a prospective examination of surgical patients reveals complication
      rates that are 2 to 4 times higher than those identified in an Institute of
      Medicine report. Almost half of these adverse events were judged
      contemporaneously by peers to be due to provider error (avoidable). Errors in
      care contributed to 38 (30%) of 128 deaths. Recognition that provider error
      contributes significantly to adverse events presents significant opportunities
      for improving patient outcomes.

PMID- 11982479
TI  - Image of the month. Zenker diverticulum.

PMID- 11982481
TI  - Railroad surgery: a forgotten chapter in the history of American surgery.

PMID- 11982482
TI  - Role of oxidative stress in germ cell apoptosis induced by di(2
      ethylhexyl)phthalate.
AB  - Phthalate esters have been used extensively as plasticizers of synthetic
      polymers. Recent studies have revealed that these esters induce atrophy of the
      testis, although its pathogenesis remains unknown. The present study describes
      the possible involvement of oxidative stress in the pathogenesis of atrophy of
      the rat testis induced by di(2-ethylhexyl)phthalate (DEHP). Biochemical and
      immunohistochemical analysis revealed that oral administration of DEHP increased
      the generation of reactive oxygen species, with concomitant decrease in the
      concentration of glutathione and ascorbic acid in the testis, and selectively
      induced apoptosis of spermatocytes, thereby causing atrophy of this organ.
      Oxidative stress was selectively induced in germ cells, but not in Sertoli cells,
      treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP.
      Furthermore, MEHP selectively induced the release of cytochrome c from
      mitochondria of the testis. These results indicate that oxidative stress elicited
      by MEHP principally injured mitochondrial function and induced the release of
      cytochrome c, thereby inducing apoptosis of spermatocytes and causing atrophy of
      the testis.

PMID- 11982483
TI  - Human platelets respond differentially to lysophosphatidic acids having a highly
      unsaturated fatty acyl group and alkyl ether-linked lysophosphatidic acids.
AB  - Lysophosphatidic acid (LPA) is a physiological agonist that is produced by
      lysophospholipase D, phospholipase A(1) and phospholipase A(2) in the blood of
      animals. It exerts diverse biological actions on a broad range of animal cells.
      Specific receptors for this important agonist have been characterized. In this
      investigation, for the first time we prepared LPAs having a highly unsaturated
      fatty acyl group, such as the eicosapentaenoyl or docosahexaenoyl residue, and
      their acetylated derivatives. Human platelets aggregated more potently in
      response to the highly unsaturated acyl-LPAs than to LPAs with a C(18) fatty acyl
      group, such as an oleoyl group, while alkyl ether-linked LPAs (alkyl-LPA) had
      much stronger aggregating activity. Two positional isomers of LPAs with an
      arachidonoyl, eicosapentaenoyl or docosahexaenoyl group had equipotent
      aggregatory activity as well as the positional isomers of their acetylated
      analogues, indicating that putative LPA receptors could not distinguish the
      difference between the positional isomers. We found that platelet preparations
      from two individuals showed no aggregatory response to alkyl-LPAs, although they
      contained mRNAs for known LPA receptors in the following order of expression
      level: endothelial differentiation gene (Edg)-4>Edg-7>Edg-2. We also obtained
      evidence that 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), a
      phospholipase A(2) inhibitor, potentiated alkyl-LPA-induced platelet aggregation,
      but inhibited highly unsaturated acyl-LPA-induced platelet aggregation. These
      results indicated that human platelets express acyl-LPA-selective and alkyl-LPA
      selective receptors on their plasma membrane.

PMID- 11982484
TI  - Preparation, biochemical characterization and biological properties of
      radiolabelled N-alkylated deoxynojirimycins.
AB  - We have reductively alkylated deoxynojirimycin imino sugars using sodium
      cyanoborohydride to provide an efficient means of generating a series of N
      alkylated compounds containing 4-18 carbon side chains. The yields were greater
      than 90% using a variety of aldehydes of different chain lengths, and after
      purification were >95% pure using (1)H-NMR. Radiolabelled compounds were prepared
      using sodium cyanoborotriti-ide to selectively label the first carbon atom in the
      alkyl chain and used in protein-binding and cell- and tissue-uptake experiments.
      Protein binding was chain-length-dependent with compounds of intermediate chain
      length (C(9)-C(12)), demonstrating an equal distribution between the aqueous and
      protein-bound phase. The extent of cell uptake also increased proportionally with
      increased chain length in a time-dependent manner. When administered to mice, the
      longer alkyl-chain compounds showed reduced absorption from the intestine and a
      marked deposition of compound in the liver and brain, suggesting that the more
      hydrophobic compounds were poorly cleared by the major tissues. In tissue-culture
      cells compounds with 8 or fewer carbon atoms were non-toxic and had CC(50) (the
      concentration at which the number of cells or cell proliferation is reduced by
      50%) values greater than 1 mM. Compounds with chain lengths above C(8) showed a
      chain-length-dependent increase in cytotoxicity. N-alkylated deoxynojirimycins
      (C(4)-C(18)) were evaluated for their inhibitory effects on ceramide-specific
      glucosyltransferase and glycoprotein-processing alpha-glucosidase. Increasing the
      alkyl chain length had little effect on alpha-glucosidase activity, but
      inhibition of ceramide-specific glucosyltransferase increased 10-fold when C(4)
      and C(9)-C(18) compounds were compared. Overall these data provide further
      definition of the molecular features of alkylated imino sugars that influence
      tissue selectivity and efficacy for cellular enzyme inhibition.

PMID- 11982485
TI  - Uromodulin promoter directs high-level expression of biologically active human
      alpha1-antitrypsin into mouse urine.
AB  - We have recently shown that the regulatory sequence of the uromodulin gene,
      containing the 3.7 kb promoter, exon 1 and a part of exon 2, provided for kidney
      specific expression of the reporter lacZ gene in transgenic mice [Zbikowska,
      Soukhareva, Behnam, Chang, Drews, Lubon, Hammond and Soukharev (2002) Transgenic
      Res., in the press]. In the present study, we generated transgenic mice
      harbouring the regulatory sequence of the uromodulin gene to direct the
      expression of human alpha1-antitrypsin (alpha1AT) into urine. Of the 13 founder
      mice that tested positive by PCR, seven showed the presence of the human protein
      in their urine. The concentration of the recombinant human (rh) alpha1AT in the
      urine, estimated by using ELISA, ranged from 0.5 to 14 microg/ml in the F(0)
      generation mice, and reached up to 65 microg/ml in the F1 generation. The
      transgenically produced rh alpha1AT was found to be N-glycosylated and
      biologically active. The N-terminal sequence analysis confirmed the identity of
      the human protein and revealed that the recombinant alpha1AT was correctly
      processed with the signal peptide cleaved off. Our results demonstrate for the
      first time that the uromodulin regulatory sequence provides a very attractive
      option for the potential large-scale production of functional therapeutic
      proteins in livestock.

PMID- 11982486
TI  - Diagnostic value of high signal abnormalities on T2 weighted MRI in the
      differentiation of Alzheimer's, frontotemporal and vascular dementias.
AB  - OBJECTIVE: The occurrence of high signal abnormalities on T2 weighted images is
      strongly age related. The diagnostic value of these changes in a younger
      population with dementia is not currently known. We studied the potential of high
      signal changes on magnetic resonance imaging (MRI) in differentiating Alzheimer's
      disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) in
      younger patients. METHODS: High signal abnormalities were rated, using a
      previously validated scale, from hard copies of T2 weighted axial images of 102
      patients with AD (n=49), VaD (n=31), FTD (n=22) (mean ages 63-65 years). RESULTS:
      High signal abnormalities were widespread across AD, VaD and FTD. Although they
      were most frequent and most severe in the VaD group only lacunes and grade III
      deep white matter hyperintensities (DWMH) were specific for these patients.
      CONCLUSIONS: High signal changes on T2 weighted images on MRI are common across
      degenerative (AD and FTD) and vascular dementias. Although lacunes and grade III
      DWMH are specific for VaD, the low sensitivities (sensitivities: for lacunes,
      0.32; for grade III DWMH, 0.16) limit their use as diagnostic markers for VaD.
      High signal changes on MRI should be interpreted with caution in dementias. Their
      presence, even in younger patients, should not deter one from diagnosing AD or
      FTD.

PMID- 11982487
TI  - Comparing two programs of cognitive training in Alzheimer's disease: a pilot
      study.
AB  - OBJECTIVES: To evaluate the efficacy of two different procedures of individual
      cognitive training in mild to moderate Alzheimer's Disease (AD). MATERIAL AND
      METHODS: Twenty-two AD patients entered the study. We compared stimulation of
      procedural memory (group 1) with training of partially spared cognitive functions
      (group 2). Assessment included: neuropsychological tests, scales, and the
      Functional Living Skills Assessment (FLSA), a standardized battery built to
      directly evaluate patients' performance in everyday life. RESULTS: We observed a
      significant improvement for both groups after training in FLSA total score
      (P=0.005) and subscales. For group 1, we also found a slightly improved
      performance in two tests: Attentional Matrices (P=0.041), and Verbal Fluency for
      Letters (P=0.059). After 3 months, patients' results showed a tendency to regress
      to the pre-training level. CONCLUSION: Both AD groups showed a substantial
      improvement after training in a direct performance measure of everyday
      functioning. However, results at neuropsychological tests suggest that training
      activities of daily living (supported by procedural memory) may be more effective
      than stimulating "residual" cognitive functions.

PMID- 11982488
TI  - Hypothalamic-pituitary-adrenal axis function and cytokine production in multiple
      sclerosis with or without interferon-beta treatment.
AB  - OBJECTIVES: Pro-inflammatory cytokines mediate brain damage in multiple sclerosis
      (MS); they can also influence the hypothalamic-pituitary-adrenal (HPA) axis
      function. We evaluated the possible abnormalities of HPA axis function in
      relapsing-remitting MS (RR-MS). MATERIAL AND METHODS: IFN-gamma, TNF-alpha and IL
      6 production by ex-vivo lymphocytes from 10 normal volunteers and 10 RR-MS
      patients before and during IFN-beta therapy was assessed; pituitary-adrenal
      function was evaluated by means of CRH and ACTH stimulation tests. RESULTS: In
      untreated patients the production of IFN-gamma, TNF-alpha, IL-6 was increased,
      and was significantly decreased by IFN-beta. Neither basal, nor stimulated ACTH,
      cortisol, DHEA, DHEAs, 17-alpha-OH-progesterone levels differed between controls
      and RR-MS patients, both before and during treatment. Moreover, no correlation
      was found between endocrine and immune parameters. CONCLUSION: In MS the HPA axis
      function seems normal and not influenced by IFN-beta treatment. This result is
      discussed in relation to the increased production of pro-inflammatory cytokines
      found in this disease.

PMID- 11982489
TI  - Immunoserological changes in the cerebro-spinal fluid and serum in systemic lupus
      erythematosus patients with demyelinating syndrome and multiple sclerosis.
AB  - The aim of the present study was to investigate the role of antinuclear and
      antiphospholipid antibodies in the pathogenesis of systemic lupus erythematosus
      (SLE) with demyelinating syndrome and several forms of multiple sclerosis (MS).
      Paired samples of serum and cerebrospinal fluid (CSF) were investigated using
      laser nephalometric and enzyme linked immunosorbant assay (ELISA) methods, and
      the parameters of intrathecal synthesis were calculated. Elevation of the
      concentrations of antiribosomal P protein antibodies in the CSF and serum, and
      intrathecal synthesis anticardiolipin (aCL) antibodies were characteristic in all
      patient groups. The immunoserological changes were more pronounced in the SLE
      patients. A similar pathogenetic role of antiphospholipid antibodies in central
      nervous system (CNS) damage in SLE patients with demyelinating syndrome and of MS
      patients can be assumed.

PMID- 11982490
TI  - Parkinson syndrome as a manifestation of mitochondriopathy.
AB  - OBJECTIVES: Although there is growing evidence for a relation between Parkinson
      syndrome (PS) and mitochondriopathy (MCP), little is known about the frequency of
      PS in MCP. MATERIAL AND METHODS: This study assessed the frequency of PS in
      patients with MCP, the phenotype of these patients, and their response to anti
      Parkinson medication, during a 1-year period. RESULTS: Between April 1999 and
      March 2000 PS was diagnosed in nine of 76 patients with MCP (12%). The frequency
      of MCP among 144 patients with PS attending the department during the
      investigational period was 6.3%. Systems most frequently affected by the MCP in
      the nine patients were the peripheral nervous system, central nervous system,
      endocrinium, heart, intestines, eyes, ears and kidneys. PS in MCPs responded well
      to amantadine, L-DOPA, dopamine agonists and catechole-o-methyl-transferase
      inhibitors. CONCLUSION: Twelve per cent of the patients with MCP have phenotypic
      features of PS and 6% of the patients with PS have features of MCP. MCP patients
      with PS frequently show multisystem involvement. PS in MCP responds well to anti
      Parkinson medication.

PMID- 11982491
TI  - Clinical and electrophysiological aspects of distal ulnar neuropathy.
AB  - OBJECTIVES: To evaluate the use of fixed distance side to side comparison of
      abductor digiti minimi (ADM) and first dorsal interosseous (FDI) compound muscle
      action potential (CMAP) studies in the diagnosis of distal ulnar neuropathy.
      MATERIALS AND METHODS: Thirty normal controls underwent ADM and FDI CMAP studies
      bilaterally at a fixed ADM recording to stimulating point distance of 6 cm. Side
      to side mean latency differences to both muscles were calculated. Twenty patients
      with suspected unilateral distal ulnar neuropathy from routine nerve conduction
      studies had positive results when compared with controls. RESULTS: The upper
      limit of normal for side to side mean latency difference at 3 SD above the mean
      was 0.394 and 0.474 ms for ADM and FDI, respectively. All 20 patients had side to
      side mean CMAP latency difference above 3 SDs in the ADM, FDI or both muscles.
      Fifty percent of cases had involvement of the superficial sensory branch.
      CONCLUSIONS: Fixed distance side to side CMAP latency comparison is a useful
      electrodiagnostic adjunct for distal ulnar neuropathy. Trauma was the most common
      aetiology in the 20 reported cases. Correlation was found between aetiological
      factors and sites of lesions as localized with this method.

PMID- 11982492
TI  - Magnetic resonance imaging in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: We aimed to investigate the importance of magnetic resonance imaging
      for the diagnostic process of the upper motor neuron involvement. MATERIAL AND
      METHODS: Fifteen patients (Group 1) who were diagnosed with amyotrophic lateral
      sclerosis in the neurology department of the Sisli Etfal Hospital and 20 controls
      (Group 2) entered the study. Magnetic resonance imaging examinations were
      performed in the radiology clinic of the same hospital. T2 and proton density
      weighted axial images were obtained. These images were evaluated by two blind
      radiologists. The radiologists looked for two signs: the presence of a low signal
      intensity at the precentral cortex and the presence of symmetrical rounded foci
      of high signal intensity within the internal capsule on both T2 and proton
      density weighted images. RESULTS: For the first sign there was no statistically
      significant difference between the two groups but for the latter one there was a
      statistically significant difference. CONCLUSION: We think that the presence of
      the latter sign may make it possible for the radiologists to help the clinicians
      further in this difficult and confusing diagnosis.

PMID- 11982493
TI  - Photoparoxysmal responses in non-epileptic children in long-term follow-up.
AB  - OBJECTIVES: To evaluate the photoparoxysmal responses (PPR) in non-epileptic
      children and adolescents in long-term follow-up. MATERIALS AND METHODS: We
      studied 14 non-epileptic children who showed PPR without any other
      electroencephalographic (EEG) abnormalities. RESULTS: One subjects was lost after
      1 year of follow-up. At the final follow-up, four of the 13 patients
      (approximately 30%) did not show any PPR or other epileptic discharges, while in
      other children PPR continued to be present. The age of the disappearance of PPR
      in these four patients ranged from 1.1 to 5.9 years from the first evaluation. No
      patients suffered from epileptic seizures during the whole period of follow-up.
      CONCLUSION: Our study confirms that PPR can be present in the EEG of non
      epileptic children and adolescents and demonstrates that this EEG change is not
      related to the presence of seizures and must not be considered a marker for the
      developing of epilepsy.

PMID- 11982494
TI  - Expression of Bcl-2 in inclusion body myositis.
AB  - OBJECTIVES: On the background of the possible role of the anti-apoptotic protein
      Bcl-2 to inhibit apoptosis induced by the Fas/Fas ligand system in inflammatory
      myopathies we investigated the expression of Bcl-2 in inclusion body myositis
      (IBM). MATERIAL AND METHODS: We examined muscle tissue from seven IBM patients
      and controls by immunocytochemistry using antibodies against Bcl-2, Fas (a member
      of the tumor necrosis factor receptor family) and the regeneration marker, neural
      cell adhesion molecule (N-CAM). We also investigated the occurrence of DNA
      fragmentation by the terminal deoxynucleotidyl transferase (TdT)-mediated
      deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL)-method. RESULTS: Both
      Bcl-2 and Fas were up-regulated in muscle fibers in IBM and disease controls. Bcl
      2 was expressed by regenerating muscle fibers while Fas was expressed by non
      regenerating muscle fibers associated with inflammatory cell infiltrates. Bcl-2
      and Fas were also expressed by inflammatory cells. There were scattered TUNEL
      positive nuclei and most of these appeared to be inflammatory cells. CONCLUSION:
      The low occurrence of apoptotic myonuclei is not related to Bcl-2 expression,
      which is confined to regenerating muscle cells in IBM and other myopathies.

PMID- 11982495
TI  - A case of acquired stuttering resulting from left parietal infarction.
AB  - OBJECTIVE: Acquired stuttering is uncommon, and is reported anecdotally after
      head injury and cerebrovascular diseases. Although this entity is described to
      occur in lesions of dominant hemisphere, it is rarely shown to occur in non
      dominant hemispheric and subcortical lesions, too. Therefore we described a case
      with this rare syndrome and we discussed the possible mechanisms, lesion
      locations and medical treatment of stuttering according to previous reports. CASE
      REPORT: A 61-year-old right-handed man with sudden onset of right hemiparesia and
      stuttering without aphasia is reported. There was a circumscribed cortical
      infarction in the left parietal cortex on computerized tomography (CT) and
      magnetic resonance imaging (MRI) showed a recent infarct. Single photon emission
      computed tomography (SPECT) images evidenced perfusion abnormalities in the same
      region. He never stuttered before and has no family history of stuttering. He has
      been maintained on antiaggregant and paroxetine treatment. CONCLUSION: A rare
      presentation of stroke associated with stuttering is reported and the treatment
      of stuttering with paroxetine is discussed.

PMID- 11982496
TI  - Clinical, electrophysiological, and serological overlap between Miller Fisher
      syndrome and acute sensory ataxic neuropathy.
AB  - We report a patient with severe sensory ataxia, areflexia, and ophthalmoplegia
      with preservation of limb muscle strength. Electrophysiological examinations
      revealed peripheral sensory nerve involvement. A serological examination showed
      the elevation of IgG antibodies to various b-series gangliosides as well as GT1a.
      These indicated that this case is an overlap between acute sensory ataxic
      neuropathy and Miller Fisher syndrome. Autoantibody is implicated as potential
      pathogenic agents in some cases of acute sensory ataxic neuropathy.

PMID- 11982497
TI  - Vascular parkinsonism--neuropathological findings.

PMID- 11982498
TI  - Twenty-four-hour non-invasive monitoring of systemic haemodynamics and cerebral
      blood flow velocity in healthy humans.
AB  - Acute short-term changes in blood pressure (BP) and cardiac output (CO) affect
      cerebral blood flow (CBF) in healthy subjects. As yet, however, we do not know
      how spontaneous fluctuations in BP and CO influence cerebral circulation
      throughout 24 h. We performed simultaneous monitoring of BP, systemic
      haemodynamic parameters and blood flow velocity in the middle cerebral artery
      (MCAV) in seven healthy subjects during a 24-h period. Finger BP was recorded
      continuously during 24 h by Portapres and bilateral MCAV was measured by
      transcranial Doppler (TCD) during the first 15 min of every hour. The subjects
      remained supine during TCD recordings and during the night, otherwise they were
      seated upright in bed. Stroke volume (SV), CO and total peripheral resistance
      (TPR) were determined by Modelflow analysis. The 15 min mean value of each
      parameter was assumed to represent the mean of the corresponding hour. There were
      no significant differences between right vs. left, nor between mean daytime vs.
      night time MCAV. Intrasubject comparison of the twenty-four 15-min MCAV
      recordings showed marked variations (P < 0.001). Within each single 15-min
      recording period, however, MCAV was stable whereas BP showed significant short
      term variations (P < 0.01). A day-night difference in BP was only observed when
      daytime BP was evaluated from recordings in the seated position (P < 0.02), not
      in supine recordings. Throughout 24 h, MCAV was associated with SV and CO (P <
      0.001), to a lesser extent with mean arterial pressure (MAP; P < 0.005), not with
      heart rate (HR) or TPR. These results indicate that in healthy subjects MCAV
      remains stable when measured under constant supine conditions but shows
      significant variations throughout 24 h because of activity. Moreover, changes in
      SV and CO, and to a lesser extent BP variations, affect MCAV throughout 24 h.

PMID- 11982499
TI  - Adenosine induces prolonged anti-beta-adrenergic effects in guinea-pig papillary
      muscle.
AB  - A sustained anti-beta-adrenergic effect of adenosine has been reported. This
      study was initiated to investigate this topic and especially elucidate the role
      of protein kinase C (PKC). Contractile force amplitude and action potential
      duration at 90% repolarization (APD90) were measured in guinea-pig papillary
      muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols
      contained 30 min exposure to the test agents adenosine 33 microm (ado), adenosine
      + PKC-inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC-activator 1,2
      dioctanoyl-sn-glycerol 10 microm (DOG) and alpha-agonist phenylephrine 5 microm
      (phe). Isoproterenol was given at the end of test exposure and after 15 min
      washout. Results are mean +/- SEM of percentage-change, P < or = 0.05 considered
      significant and labelled *. The first isoproterenol challenge significantly
      increased contractile force (27 +/- 7%*) in the control group. Responses in the
      test groups were 2 +/- 4 (ado), 1 +/- 5 (ado + BIM), 14 +/- 4* (DOG), 0 +/- 2%
      (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3
      +/- 8 (ado), 23 +/- 5* (ado + BIM), 13 +/- 5* (DOG), 15 +/- 7% (phe) increase in
      test groups compared with 22 +/- 5%* increase in contractile force in the control
      group. After 45 min washout of adenosine the inotropic response was still
      significantly reduced compared with control (29 +/- 4 vs. 79 +/- 8%*).
      Isoproterenol stimulation shortened APD90 in controls at both time points (5 +/-
      1%* and 4 +/- 1%*), with no significant shortening in test groups. Adenosine
      induces sustained anti-beta-adrenergic effects on contractile force as well as
      APD90. A role for PKC in signal transduction is supported with respect to
      contractile force.

PMID- 11982500
TI  - Glucose transporter gene expression in freshly isolated and cultured rat
      pneumocytes.
AB  - Alveolar epithelium in situ takes up luminal glucose by cotransport with sodium.
      Cultured alveolar type II pneumocytes have only sodium-independent glucose
      uptake. It is unclear which isoforms are responsible for glucose transport in
      these cells and why sodium-glucose cotransport activity disappears during
      culture. GLUT1, GLUT4, GLUT5 and SGLT1 mRNA were detected in freshly isolated rat
      alveolar type II cells by reverse transcriptase-polymerase chain reaction. We
      show that SGLT1 mRNA was 90% lower in cells cultured in plastic wells for 2 or 4
      days than in freshly isolated cells. mRNAs coding for the facilitated
      transporters were reduced from 40% (GLUT1) and 75% (GLUT4 and GLUT5) in cultured
      cells. Cells cultured at the air-liquid interface better preserved their
      phenotype as attested by significantly higher surfactant-associated protein mRNA
      levels. However, these cells had no higher GLUT1 and SGLT1 gene expression. Thus,
      alveolar type II cells lose sodium-glucose cotransport activity in part because
      of a decrease in mRNA levels. These changes in gene expression and/or mRNA
      stability may be an additional consequence of the shift towards the type I cell
      phenotype observed in cultured type II pneumocytes.

PMID- 11982501
TI  - The neuropeptide PACAP contributes to the glucagon response to insulin-induced
      hypoglycaemia in mice.
AB  - The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is a
      neuropeptide in the autonomic nerves innervating the pancreatic islets and
      previous studies have shown that it stimulates insulin and glucagon secretion. It
      is known that autonomic nerve activation contributes to the glucagon response to
      hypoglycaemia. In the present study, we evaluated whether PACAP is involved in
      this glucagon response by examining the glucagon response to insulin-induced
      hypoglycaemia in mice genetically deleted of the specific PACAP receptor, the
      PAC1 receptor. We found that insulin (1 U kg-1 ip) reduced circulating glucose to
      a hypoglycaemic level of approximately 2.5 mmol L-1 in PAC1R-/- mice and their
      wild-type counterparts with no difference between the groups. However, the
      glucagon response to this hypoglycaemia was markedly impaired in the PAC1R-/-
      mice. Thus, after 120 min, plasma glucagon was 437 +/- 79 ng L-1 in wild-type
      mice vs. only 140 +/- 36 ng L-1 in PAC1R-/- mice (P=0.004). In contrast, the
      glucagon response to intravenously administered arginine (0.25 g kg-1) was the
      same in the two groups of mice. We conclude that PACAP through activation of PAC1
      receptors contribute to the glucagon response to insulin-induced hypoglycaemia.
      Therefore, the glucagon response to hypoglycaemia is dependent not only on the
      classical neurotransmitters but also on the neuropeptide PACAP.

PMID- 11982502
TI  - Okadaic acid inhibits relaxant neural transmission in rat gastric fundus in
      vitro.
AB  - The aim of the present study was to characterize the influence of the phosphatase
      type 1 and 2A inhibitor okadaic acid on non-adrenergic, non-cholinergic (NANC)
      neurotransmission in the rat gastric fundus. Okadaic acid (10-6 M), an inhibitor
      of protein phosphatases 1 and 2A, did not show any influence on the basal tonus
      or on a contraction plateau induced by 5-HT (10-7 M) within 30 min of
      observation. When okadaic acid (10-6 M) was applied 10 min prior to 5-HT (10-7
      M), the contraction plateau of serotonin was unchanged. To investigate the
      inhibitory neurotransmission, the muscle strips were pre-contracted using 5-HT
      (10-7 M), and inhibitory stimuli were applied at the contraction plateau, which
      was stable over 30 min. The inhibitory effects of vasoactive intestinal peptide
      (VIP), nitric oxide (NO) and electrical field stimulation (EFS, 40 V, 0.5 ms,
      frequencies ranging from 0.5 to 16 Hz) were examined. When okadaic acid (10-6 M)
      was applied prior to EFS-induced NANC relaxation, significant attenuation of the
      inhibitory response was demonstrated (16 Hz: control: -92.4 +/- 1.9%; okadaic
      acid 10-7 M: -60.7 +/- 6.1%; okadaic acid 10-6 M: -25.3 +/- 3.4%; n=11; P <
      0.01). By contrast, neither the concentration-dependent inhibitory actions of VIP
      (10-11-10-8 M) (VIP 10-8 M: -100%; VIP 10-8 M + okadaic acid 10-6 M: -89.9 +/-
      8.3%; n=8; n.s) nor that of diethylamine nitric oxide (DEA-NO) (3 x 10-7-10-4 M)
      (DEA-NO 10-4 M: -95.3 +/- 8.4%; DEA-NO 10-4 M + okadaic acid 10-7 M: -98.3 +/-
      6.3%; DEA-NO 10-4 M + okadaic acid 10-6 M: 96.5 +/- 7.6%; n=9; n.s.) on 5-HT
      induced contraction were altered by pre-incubation with okadaic acid (10-6 M).
      This is the first report that supports the concept that protein phosphatases 1
      and 2A may contribute to the regulation of rat gastric fundus motility. The
      protein phosphatase inhibitor okadaic acid significantly reduces electrically
      induced inhibitory NANC responses, while leaving direct muscular effects of the
      inhibitory NANC neurotransmitters VIP and NO unaffected - suggesting a neural
      site of action. The potential roles of protein phosphatases on NANC
      neurotransmission remain to be clarified in detail, as this might offer a new
      pathway for modulating smooth-muscle function.

PMID- 11982503
TI  - Interaction of exercise and diet on GLUT-4 protein and gene expression in Type I
      and Type II rat skeletal muscle.
AB  - We determined the interaction of exercise and diet on glucose transporter (GLUT
      4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum
      longus (EDL)] skeletal muscle. Forty-eight Sprague Dawley rats were randomly
      assigned to one of two dietary conditions: high-fat (FAT, n=24) or high
      carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one
      of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill
      running (4 sessions week-1 of 1000 m @ 28 m min-1, RUN, n=16). Eight trained rats
      were killed after their final exercise bout for determination of GLUT-4 protein
      and mRNA expression: the remainder were killed 48 h after their last session for
      measurement of muscle glycogen and triacylglycerol concentration. GLUT-4 protein
      expression in NT rats was similar in both muscles after 8 weeks of either diet.
      However, there was a main effect of training such that GLUT-4 protein was
      increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in
      animals fed with CHO (P < 0.05). There was a significant diet-training
      interaction on GLUT-4 mRNA, such that expression was increased in both the soleus
      (100% upward arrowP < 0.05) and EDL (142% upward arrowP < 0.01) in CHO-fed
      animals. Trained rats fed with FAT decreased mRNA expression in the EDL (
      downward arrow 45%, P < 0.05) but not the soleus ( downward arrow 14%, NS). We
      conclude that exercise training in CHO-fed rats increased both GLUT-4 protein and
      mRNA expression in type I and type II skeletal muscle. Despite lower GLUT-4 mRNA
      in muscles from fat-fed animals, exercise-induced increases in GLUT-4 protein
      were largely preserved, suggesting that control of GLUT-4 protein and gene
      expression are modified independently by exercise and diet.

PMID- 11982504
TI  - Increased phasic activity of dopaminergic neurones in the rat ventral tegmental
      area following pharmacologically elevated levels of endogenous kynurenic acid.
AB  - Kynurenic acid (KYNA) is an antagonist of ionotropic glutamate receptors,
      preferentially blocking the glycine-site of the N-methyl-D-aspartate (NMDA)
      receptor. In the present electrophysiological study, the firing pattern of
      dopamine (DA) neurones of rat ventral tegmental area (VTA) was investigated
      following pharmacologically elevated endogenous levels of KYNA by means of an
      inhibitor of kynurenine 3-hydroxylase (PNU 156561A). Pre-treatment with PNU
      156561A (40 mg kg-1, i.v., 5-9 h) caused a threefold increase in endogenous KYNA
      in whole brain levels and also evoked a significant increase in firing rate and
      bursting activity of VTA DA neurones. Administration of D-cycloserine (2-128 mg
      kg-1, i.v.), a partial agonist at the glycine-site of the NMDA-receptor, was
      found to reverse the increase in firing rate and bursting activity as induced by
      elevated concentrations of KYNA. The electrophysiological effects of elevated
      KYNA levels were in all essential mimicked by administration of the NMDA-receptor
      antagonist MK 801 (0.05-1.6 mg kg-1, i.v.). Thus, the effects of elevated
      endogenous brain KYNA observed in the present study are likely to be carried out
      by NMDA receptor antagonism. In conclusion, this study shows that an increase in
      endogenous KYNA levels produces significant actions on the tonic afferent control
      of the firing pattern of VTA DA neurones. Given the psychotomimetic effects of
      NMDA-receptor antagonists, e.g. phencyclidine and ketamine, the state of
      hyperactivity of mesocorticolimbic DA system induced by elevated levels of KYNA
      may represent a pathophysiological condition analogous to that seen in
      schizophrenic patients.

PMID- 11982505
TI  - Mechanisms of transjunctional transport of NaCl and water in proximal tubules of
      mammalian kidneys.
AB  - Tight junctions and the intercellular space of proximal tubules are not
      accessible to direct measurements of fluid composition and transport rates, but
      morphological and functional data permit analysis of diffusion and osmosis
      causing transjunctional NaCl and water transport. In the S2 segment NaCl diffuses
      through tight junctions along a chloride gradient, but against a sodium gradient.
      Calculation in terms of modified Nernst-Fick diffusion equation after eliminating
      electrical terms shows that transport rates (300-500 pmol min-1 mm-1 tubule
      length) and transepithelial voltage of +2 mV are in agreement with observations.
      Diffusion coefficients are Dtj=1500 microm2 s-1 in the S1 segment, and Dtj=90-100
      microm2 s-1 in the S2 segment where apical intercellular NaCl concentration is
      132 mM, 1 mM below complete stop (Dtj=0 and Donnan equilibrium). Tight junctions
      with gap distance 6 A are impermeable to mannitol (effective molecular radius 4
      A); reflection coefficients are sigma=0.92 for NaHCO3 and sigma=0.28 for NaCl,
      because of difference in anion size. The osmotic force is provided by a
      difference in effective transjunctional osmolality of 10 mOsm kg-1 in the S1
      segment and 30 mOsm kg-1 in the S2 segment, where differences in transjunctional
      concentration contribute with 21 mOsm kg-1 for NaHCO3 and -4 mOsm kg-1 for NaCl.
      Transjunctional difference of 30 mOsm kg-1 causes a volume flow of 2 nL min-1 mm
      1 tubule length. Luminal mannitol concentration of 30 mM stops all volume flow
      and diffusive and convective transport of NaCl. In conclusion, transjunctional
      diffusion and osmosis along gradients generated by transcellular transport of
      other solutes account for all NaCl transport in proximal tubules.

PMID- 11982506
TI  - Mechanisms of intercellular hypertonicity and isotonic fluid absorption in
      proximal tubules of mammalian kidneys.
AB  - The main purpose of this theoretical analysis (second of two articles) is to
      examine whether transjunctional diffusion of NaCl causes intercellular
      hypertonicity, which permits transcellular water transport across solute
      impermeable lateral cell membranes until osmotic equilibration. In the S2 segment
      with tubular NaCl concentration 140 mM, the calculated apical intercellular NaCl
      concentration is c0 approximately 132 mM, which exceeds peritubular NaCl
      concentration by 12 mM or 22 mOsm kg-1. Variations in volume flow, junctional
      reflection coefficient (sigmaNaCl = 0.25-0.50), gap distance (g = 6-8 A),
      junctional depth (d = 18-100 A), intercellular diffusion coefficient (DLIS=500
      1500 microm2 s-1) and hypothetical active NaCl transport alter c0 only by a
      fraction of 1 mM. However, dilution and back-leakage of NaHCO3 lower apical
      intercellular hyperosmolality to approximately 18 mOsm kg-1. Water transport
      through solute-impermeable lateral cell membranes continues until intercellular
      and cellular osmolalities are equal. Transcellular and transjunctional volume
      flow are of similar magnitude (2 nL min-1 mm-1 tubule length) in the S2 segment.
      Thus, diffusion ensures isotonic absorption of NaCl. Two-thirds of NaHCO3 and
      other actively transported sodium salts are extruded into the last third of the
      exponentially widening intercellular space where the exposure time is only 0.9 s.
      Osmotic equilibration is dependent on aquaporins in the cell membranes. If
      permeability to water is low, transcellular water transport stops; tubular fluid
      becomes hypotonic; NaCl diffusion diminishes, but transjunctional water transport
      remains unaltered as long as transcellular transport of NaHCO3 and other solutes
      provides the osmotic force.

PMID- 11982507
TI  - Surgical margins for melanoma: is 2 cm too much?

PMID- 11982508
TI  - Exploration of the common bile duct in the era of laparoscopic cholecystectomy.

PMID- 11982509
TI  - Tumour implantation following laparoscopy using different insufflation gases.
AB  - BACKGROUND: Because of the possibility of intraperitoneal seeding and port-site
      recurrences following laparoscopic surgery, the role of laparoscopy in cancer
      surgery remains controversial. Previous experimental studies have suggested that
      chemical, metabolic and immunological changes following carbon dioxide (CO2)
      insufflation may be responsible for this phenomenon. Earlier experimental studies
      done by the University of Adelaide Department of Surgery have also shown that
      helium insufflation is associated with none of the adverse changes brought about
      by CO2 insufflation. Helium insufflation is also associated with lower rates of
      intra-abdominal tumour spread. The aim of this study was to determine whether
      these identified benefits apply to inert gases in general. METHODS: Twenty-four
      Dark Agouti rats were randomized to undergo laparoscopy with 40 min insufflation
      using one of the following four gases (six rats in each group); CO2, helium,
      argon and nitrogen. A tumour cell suspension was injected into the abdominal
      cavity at the beginning of laparoscopy. The rats were killed 7 days after
      surgery, and the peritoneal cavity and port sites were examined for the presence
      of tumour. RESULTS: Rats undergoing helium insufflation, had the least number of
      port-site recurrences and the least amount of intraperitoneal tumour spread.
      Argon and nitrogen pneumoperitoneum were associated with a large number of port
      site recurrences and widespread tumour seeding. The effect of CO2 insufflation
      was intermediate. CONCLUSION: The choice of insufflation gas influences the
      incidence of port-site metastases and the degree of intraperitoneal tumour spread
      following laparoscopic cancer surgery. The reduced port-site recurrences and
      intraperitoneal spread that followed helium pneumoperitoneum is likely to be a
      unique property of this gas rather than a property of inert gases in general.

PMID- 11982511
TI  - Laparoscopic transcystic bile duct stenting in the management of common bile duct
      stones.
AB  - BACKGROUND: The management of patients with common bile duct stones associated
      with stones in the gall bladder remains controversial. METHODS: Over the three
      year period from 1996 to 1999, patients with cholelithiasis and known
      choledocholithiasis, or choledocholithiasis found at laparoscopic
      cholecystectomy, were initially treated by placing a stent across the sphincter
      of Oddi. The stent was pushed along a guide wire through the cystic duct and then
      down the common bile duct, before the cystic duct was closed. Subsequently, the
      stent was used to facilitate performance of a needle knife endoscopic
      sphincterotomy. The stent was then removed, a cholangiography was performed and
      the common bile duct was cleared. Patients with persistent jaundice usually had a
      preoperative endoscopic retrograde cholangio-pancreatography. RESULTS:
      Transcystic stenting was the 'intention-to-treat' basis of therapy for 56 of the
      patients. The placement of the stent only failed once when the stent became
      trapped in the cystic duct. Complications of the operation included: pain and
      jaundice (n = 2), cholangitis (n = 1), and pulmonary embolus (n = 1). The median
      postoperative hospitalization was 2 days (range: 1-15). Five further patients had
      common bile duct stones removed via a choledochotomy; a stent was placed through
      the choledochotomy before its closure. The selective common bile duct cannulation
      rate at the first endoscopic retrograde cholangio-pancreatography, was 98%. A
      second endoscopic retrograde cholangio-pancreatography was required in 15% of
      patients. The only complication of all the endoscopic procedures was a single
      case of mild cholangitis; there were no cases of pancreatitis. CONCLUSION: A
      treatment option open to all surgeons for non-jaundiced patients with known
      choledocholithiasis or choledocholithiasis found at operative cholangiogram, is
      the transcystic stenting of the sphincter of Oddi at the time of laparoscopic
      cholecystectomy. At a subsequent sitting, the common bile duct can be safely
      cleared endoscopically using a sphincterotomy facilitated by the stent.

PMID- 11982512
TI  - Rectal cancer in Victoria in 1994: patterns of reported management.
AB  - BACKGROUND: A retrospective survey of medical practitioners was conducted to
      describe the management of patients newly diagnosed with rectal cancer in 1994,
      prior to the publication of best practice guidelines. METHODS: A sample of 908
      patients with rectal cancer diagnosed between 1 January and 31 December 1994 was
      identified from the Victorian Cancer Registry. Questionnaires were then sent to
      the treating doctor(s) for completion. The topics covered by the questionnaires
      included: reported management by method of diagnosis; staging investigations; and
      treatment by surgery, chemotherapy and radiotherapy. RESULTS: Seven hundred and
      twenty-six (80%) of 908 eligible patients were surveyed. Surgery was the primary
      treatment in 681 (93.8%) with curative intent in 483 (70.9%) of these cases. One-
      third (163; 33.7%) of curative cases were pathologically staged as Dukes' C.
      Almost all patients (96%) were symptomatic, and three-quarters were referred by
      general practitioners to 166 surgeons. One-third (221; 32.5%) underwent liver
      computed tomography or ultrasound, and only three cases had transrectal
      ultrasound. Restorative anterior resection was the most common surgical procedure
      (431; 63.3%) with 160 (23.5%) and 34 (5.0%) patients being managed with
      abdominoperineal resections and local excision, respectively. Chemotherapy and
      radiotherapy were administered as part of the initial management to 216 (31.7%)
      and 171 (25.1%) patients, respectively. In five of the 171 cases, radiotherapy
      was given preoperatively. CONCLUSIONS: There was considerable variation in
      preoperative assessment. Staging was less complete than expected by today's
      standards. The diversity of surgical techniques observed may reflect both the
      lack of clinical trials and disparity in surgical training and experience.
      Referral to stomal therapists, and medical and radiation oncologists was lower
      than would now be expected, as was the use and timing of adjuvant therapies.
      These findings will be useful as a baseline for comparison with subsequent
      surveys conducted since the introduction of evidence-based guidelines.

PMID- 11982513
TI  - Audit of definitive colorectal surgery in patients with early and advanced
      colorectal cancer.
AB  - BACKGROUND: The role of surgery in patients with advanced colorectal cancer may
      be questioned in the era of specialized intensive palliative care. Should
      patients with advanced disease be advised against surgery because of the risks of
      the surgery itself? In this study, the perioperative outcomes in patients
      undergoing definitive surgery for early (Dukes' stages A, B and C) and advanced
      colorectal cancer (stage D) were examined. METHODS: All patients undergoing
      definitive surgery for colorectal cancer during a 15-year period were identified.
      Details of tumour site and stage, surgery performed, perioperative complications
      and postoperative mortality were compared. RESULTS: A total of 374 patients
      underwent definitive surgery. There were 193 men, a male : female ratio of 1:0.9.
      Seventy-one patients had advanced disease. There were no differences between the
      early and advanced groups in perioperative requirements for either blood or total
      parenteral nutrition. In the advanced group, more operations were performed as
      emergencies than in the early group (32.4 vs 17.5%; P < 0.01) and more patients
      presented with bowel obstruction in the advanced group (23.9 vs 10.2%; P < 0.01).
      There were no site differences between the early and advanced groups and no
      differences between the operations performed except that endo-anal destruction
      was not performed in advanced patients. There were no differences in
      perioperative morbidity or mortality in the groups studied. CONCLUSION: Resection
      rates, operation type and postoperative morbidity and mortality were similar in
      patients with both early and advanced colorectal cancers. In terms of
      perioperative outcome, the presence of advanced cancer, per se, should not,
      therefore, be a justification to decline surgery.

PMID- 11982514
TI  - Antibiotic prophylaxis in elective colorectal surgery.
AB  - BACKGROUND: Antibiotics are often administered in elective colorectal surgery to
      prevent wound infection. The tendency for surgeons to prolong the administration
      of prophylactic antibiotic therapy in the postoperative period is a well-known
      fact. The aim of this study was to elucidate the pattern of prophylactic
      antibiotic utilization in elective colorectal surgery and to determine if
      evidence-based medicine is employed in relation to this practice. METHODS: A
      cross-sectional study encompassing general surgeons performing elective
      colorectal surgery was performed. Questionnaires were distributed to 144 surgeons
      (national, academic and private health care). Questions pertaining to the type,
      timing and duration of antibiotic administration were asked. The prevalence of
      wound infection audit rate and whether or not there were specific guidelines
      related to antibiotic administration were also determined. RESULTS: The response
      rate obtained was 67% (n = 96). Although evidence from the current medical
      literature and recommended national guidelines support the use of single-dose
      prophylactic antibiotics, 72% of the respondents used more than a single dose.
      Forty surgeons (42%) claimed that their prescribing practice was supported by the
      medical literature, 31 respondents (32%) based their practice on hospital
      guidelines and personal preference was cited as a reason by 21 surgeons (22%).
      The remaining four respondents (4%) used a similar scheduling policy to that
      practiced by their colleagues in relation to antibiotic administration. There was
      no significant difference in antibiotic dose scheduling between national, private
      and university academic institutions (P = 0.85). CONCLUSIONS: These results
      suggest that a significant proportion of surgeons administer excessive and
      unnecessary doses of antibiotics in elective colorectal surgery. Further studies
      are required to uncover the reasons but lack of appropriate guidelines and
      failure to exercise evidence-based medicine are major factors that account for
      this practice.

PMID- 11982516
TI  - Aortic aneurysm repair in a peripheral setting: audit 100 consecutive cases.
AB  - BACKGROUND: Subspecialization of vascular surgery and the advent of endovascular
      techniques for aortic aneurysm repair have had a large impact on the approach to
      aortic surgery in main centres. Centralization of vascular surgery has been
      proposed to lower mortality and morbidity rates. More recently, clinical
      governance standards have been set by professional bodies for acceptable adverse
      outcome rates in aortic surgery. A peripheral general surgeon's experience with
      aortic surgery is reviewed in the present report in order to identify the local
      adverse outcome rates, and to relate them to case data and governance
      recommendations. METHODS: A retrospective audit of 100 cases of elective and
      emergency aortic aneurysm repair (performed by the senior author over a 10-year
      period) was undergone for the present review. Demographic and outcome data were
      recorded, and a data analysis was performed to identify factors related to
      mortality. Significance was tested using chi-squared analysis. RESULTS:
      Postoperative mortality rates were 1.7% for elective cases and 21% for acute
      cases. Mortality was related to rupture of the aneurysm, blood loss and American
      Society of Anesthetists score > 3. CONCLUSION: Morbidity and mortality rates from
      this audit compare favourably with those from larger vascular units. They are
      well within the accepted clinical governance rates, although the latter do not
      account for any case mix variation which may exist between peripheral and
      tertiary referral centres. These results support the continuation of aortic
      aneurysm surgery in peripheral centres.

PMID- 11982517
TI  - Risks to feet in the top end: outcomes of diabetic foot complications.
AB  - BACKGROUND: The foot complications of diabetes are severe, disabling, costly and
      common in the Northern Territory. An understanding of the pathogenesis, the
      disease spectrum and treatment efficacy, however, is poor. The patterns of
      disease are documented in the present study; factors associated with good and
      poor outcomes are identified; and improved management strategies are proposed.
      METHODS: All patients presenting to the High Risk Foot Service at Royal Darwin
      Hospital between March 1997 and March 2000 were included in the present study,
      and details regarding the status of their feet, their demographics, their
      treatment and their outcomes were recorded prospectively. Logistic regression
      analysis was undertaken to determine associations between factors of interest and
      outcomes of healing and amputation. RESULTS: One hundred and twenty-six patients
      were recorded, 41% of whom had neuropathic ulcers and 63% of whom had severe
      disease at presentation. Two types of diabetic foot pathology were recognized
      that are not usually classified: acute injury without neuropathy (10%) and deep
      soft tissue infection alone (9%).Thirty-seven percent and 23% of patients
      required minor and major amputations, respectively. The total number of hospital
      bed-days was 5813. Total contact casting was associated with good healing rates
      in 16 patients. Major amputation was associated with ischaemia, severe disease at
      presentation and increasing age. CONCLUSIONS: Patterns of diabetic foot disease
      which are not commonly recognized are described in the present study; the
      severity and cost of the problem are documented; and some factors which lead to
      poor outcome, such as late presentation, are identified. Attention should be
      paid, through a multidisciplinary team, to timely referral from primary care,
      patient education, total contact casts and appropriate revascularization.

PMID- 11982518
TI  - A reappraisal of thyroid surgery under local anaesthesia: back to the future?
AB  - BACKGROUND: Thyroid surgery is usually performed under general anaesthesia.
      However, for a selected group of patients, local anaesthesia may be preferable.
      The aim of this study was to review the authors' experiences with local
      anaesthesia with regard to the safety and outcome of this approach. METHODS: A
      total of 65 consecutive patients who underwent primary thyroid surgery were
      accrued prospectively into this study from May to December 1999. A field block
      with 0.5% bupivacaine and adrenaline in 1:200 000 dilutions was given in all
      cases. In addition, light sedative and narcotics were given as necessary to
      achieve patient comfort and cooperation. The pain experienced during surgery was
      recorded using a visual analogue scoring system on a scale of 1-10. RESULTS:
      Unilateral thyroid resection was performed in 58 patients, isthmectomy in four
      patients and bilateral thyroid resection in three patients, two of which were in
      their second trimester of pregnancy diagnosed with papillary thyroid cancer.
      There were 55 women and 10 men with an average age of 38.2 years (range: 18-67
      years). No conversion to general anaesthetic was needed, and the mean operating
      time was 80 min. The postoperative recovery was quick with this technique and, of
      interest, 22 (33.9%) patients were discharged within 6 h following the surgery.
      Overall 62 (95.4%) patients were discharged in the first 24 h and three (4.6%)
      patients after 24 h. There were no significant postoperative complications
      encountered except for wound infection in two (3.1%) patients. CONCLUSIONS:
      Thyroid surgery under local anaesthesia can be performed safely in a selected
      group of patients. It offers an effective alternative approach to general
      anaesthesia and is associated with low morbidity and high levels of patient
      satisfaction.

PMID- 11982519
TI  - Bone spurs: mechanism of production of different shapes based on observations in
      Dupuytren's diathesis.
AB  - Bone spur formation on the shaft of the middle phalanx of the little finger was
      an incidental finding during surgical treatment of five cases of Dupuytren's
      contracture. The presence of such spurs in Dupuytren's contracture is not
      adequately explained in the literature. In areas of high tensile stress, such as
      the attachments of fascia and fibrous cords, bone remodels to reduce stress
      concentration and to make the stress transfer from one tissue to the other as
      smooth as possible. It cannot be regarded as the same process that is seen in
      heterotopic calcification in other sites in the body, and should be regarded
      instead as a physiological bone response to tensile stresses rather than a change
      intimately coupled with Dupuytren's disease.

PMID- 11982520
TI  - Simplified technique for laparoscopic appendectomy.
AB  - In this article, a simplified technique for laparoscopic appendectomy is
      described in which the base of the appendix is firstly divided, and then ligated
      with an endoloop. An endoloop is then passed over the appendix onto the
      mesoappendix and tightened to secure the blood supply. The appendix can then be
      freed and removed. This technique has been used by the authors in difficult
      cases, and has produced excellent results.

PMID- 11982521
TI  - Laparoscopic repair of ventral incisional hernia.
AB  - BACKGROUND: Laparoscopic repair of ventral incisional hernias was first reported
      in 1993. Since then, there have been sporadic case reports and small series
      published about this procedure, but it has not been widely adopted. Newer types
      of composite prosthetic mesh may reduce the potential problem of bowel adhesion.
      METHODS: Thirty cases of laparoscopic ventral incisional hernia repairs (carried
      out by two surgeons or their senior registrars) have been retrospectively
      reviewed and reported in this article. The data were obtained from patient
      records and subsequent phone surveys. RESULTS: Thirty patients between 29 and 82
      years (mean: 58 years) underwent this procedure. There were 14 men and 16 women.
      The average weight of the patients was 81 kg. The hernias were up to 6 or 7 cm in
      diameter. Mesh was used in 28 cases (polypropylene in 25 cases, expanded
      polytetrafluoroethylene in two cases and composite mesh in one case). Most meshes
      were laid intraperitoneally and fixed into position with laparoscopic spiral
      tacks. Twenty-nine cases were completed laparoscopically. One operation (3.3%)
      was converted to an open procedure because of severe bowel adherence to the
      hernia sac. The mean operating time was 52 min for laparoscopic ventral
      incisional hernia repairs only. All but two patients tolerated an oral diet
      within 24 h. The postoperative hospital stay ranged from 0 to 11 days, with 17
      patients (57%) staying overnight and eight patients (27%) staying another day.
      Over 80% of the patients returned to house duties within a week. There was no
      mortality, and minor complications occurred in four patients (14%). One patient
      had a small bowel obstruction treated successfully by repeat laparoscopy with
      division of fibrinous adhesions to polypropylene mesh on day four. Follow up
      ranged from 1 to 69 months (mean: 12 months). One patient did not attend follow
      up appointments. There were three cases of hernia recurrence (10%). CONCLUSION:
      The results suggest that laparoscopic repair of ventral incisional hernias is a
      safe, effective and technically feasible operation for small- to medium-sized
      hernias allowing shorter hospital stay, early recovery and resumption of normal
      activities. However, recurrence rates are comparable to open mesh hernioplasty
      especially for larger hernias.

PMID- 11982522
TI  - Melanoma: margins for error.

PMID- 11982523
TI  - Melanoma: Margins for error -- another view.

PMID- 11982524
TI  - Some thoughts on 'operative' training in general surgery.

PMID- 11982525
TI  - Purple urine bag syndrome.

PMID- 11982526
TI  - Multiple pancreatic metastases from renal cell carcinoma.

PMID- 11982527
TI  - Is a chest radiograph a satisfactory test for the correct position of a central
      line?

PMID- 11982528
TI  - Endometriosis in an episiotomy scar preceding pelvic endometriosis.

PMID- 11982529
TI  - Testicular torsion: time is the enemy.

PMID- 11982531
TI  - Failed paediatric laryngo tracheoplasty.

PMID- 11982536
TI  - First-episode mania: a neglected priority for early intervention.
AB  - OBJECTIVE: While first-episode (FE) psychosis has become an important field of
      research, FE affective psychoses, and mania in particular, have been relatively
      neglected. This paper summarizes current knowledge about FE mania and explores
      the potential for early intervention. METHOD: The main computerized psychiatric
      literature databases were accessed. RESULTS: When functional as well as
      symptomatic variables are considered, the outcome of mania is not as good as was
      formerly believed, a characteristic which is already present from the first
      episode. Various factors (lower socio-economic status, younger age at onset of
      illness, poor adherence to treatment, presence of comorbidity) have been
      identified as possible predictors of poor outcome. The prognostic value of the
      presence of psychotic symptoms and their congruence to mood, as well as the
      diagnostic subgroup, is less well established. This literature review also
      reveals striking similarities between manic and schizophreniform first episodes.
      Poor functional outcome in a significant proportion of patients following the
      first episode, high risk of suicide, high prevalence of comorbid diagnoses, worse
      outcome with a younger age at onset and with longer delay until treatment is
      initiated, and finally early presence of neuro-anatomical changes, are observed
      in both syndromes. CONCLUSIONS: This pattern justifies the development of early
      intervention strategies for FE manic patients and supports more exploratory
      research to identify prodromal symptoms, which might ultimately lead to even
      earlier focus on preventive interventions.

PMID- 11982537
TI  - Life events, stress and depression: a review of recent findings.
AB  - OBJECTIVE: To review recent empirical prospective studies on the relation between
      life event stressors and depression. METHOD: A systematic literature search
      focusing on predictive studies was carried out from 1980 to early 2001 using
      Medline, Embase and PsychInfo. RESULTS: The empirical findings for the most part
      support clinical impressions of the relation of stressors to depression but at
      the same time provide some clearer understanding in relation to differences of
      stressor impact on depression type and on index episode, relapse or recurrence.
      Twin studies now provide the strongest evidence of the relative magnitude of
      effect of environmental stressors and genetic factors: the former explains at
      least as much of the variance in depression as our genes. CONCLUSIONS: Continuing
      research into life events and depression have been fruitful especially those
      studies assessing the effect of stressors in combination with other aetiological
      variables such as genetic factors.

PMID- 11982538
TI  - Hanging, firearm, and non-domestic gas suicides among males: a comparative study.
AB  - OBJECTIVE: To identify characteristics that could distinguish males who completed
      suicide by hanging from males who completed suicide by firearms and non-domestic
      gas, and to suggest suicide prevention strategies targeted at hanging. METHOD:
      Using the psychological autopsy design, males who used hanging, firearms and non
      domestic gas were compared on a range of variables covering social,
      psychological, and health related factors and aspects of the suicide incident.
      The sample consisted of 950 males who completed suicide in Queensland, Australia,
      between 1994 and 1996. RESULTS: Compared with males who used firearms and non
      domestic gas, males who used hanging were significantly younger, less likely to
      have left a suicide note, and more likely to have been diagnosed with a psychotic
      disorder. Compared with males who used firearms, males who used hanging were
      significantly more likely to have made prior suicide attempts and have had no
      physical illness. Compared with males who used non-domestic gas, males who used
      hanging were significantly more likely to have lived with others, have had prior
      legal trouble, and have completed suicide at their residence. CONCLUSIONS: The
      results are discussed in terms of the availability and socio-cultural
      acceptability of methods. The authors suggest a possible relationship between
      impulsive traits and method choice. This proposition requires further
      investigation using alternative methodologies. Some suicide prevention measures
      targeting hanging suicides are discussed in light of the results.

PMID- 11982539
TI  - Reporting of suicide in the Australian media.
AB  - OBJECTIVE: The media monitoring project aimed to establish a baseline picture of
      the extent, nature and quality of reporting of suicide by the Australian media,
      with a view to informing future strategies intended to optimize reporting of
      suicide. METHOD: Newspaper, television and radio items on suicide were retrieved
      over 12 months. Identifying and descriptive information were extracted for each
      item. Approximately 10% of items were rated for quality, using a rating scale
      based on criteria from Achieving the Balance, a kit designed to promote awareness
      among media professionals of issues relating to suicide. The scale ranged from 0
      (poor quality) to 100 (good quality). RESULTS: Reporting of suicide was extensive
      (with 4813 items retrieved). The nature of reporting was variable. Items tended
      to be about completed suicide (rather than attempted suicide or suicidal
      ideation), and most commonly involved content related to an individual's
      experiences, policy/programme initiatives and/or suicide statistics, although
      there were differences across media types. Items showed variability across
      dimensions of quality. The majority of suicide items did not have examples of
      inappropriate language, were not inappropriately located, did not use the word
      'suicide' in the headline, and did not use explicit photographs/diagrams or
      footage. However, around half of the suicide items provided a detailed discussion
      of the method of self-harm and portrayed suicide as merely a social phenomenon.
      Where items concerned the suicide of a celebrity, reference was commonly made to
      that person's celebrity status. Most items failed to provide information on help
      services. The median total quality score was 57.1%. CONCLUSIONS: The reporting of
      suicide is extensive across all media types, and varies in nature and quality. In
      general, good items outnumber poorer items. However, there are still
      opportunities for improving media reporting of suicide.

PMID- 11982540
TI  - Emotional numbing in posttraumatic stress disorder: current and future research
      directions.
AB  - OBJECTIVE: Despite being understudied and poorly understood relative to the
      chronic fear, anxiety and other aversive emotional states that occur in the
      immediate aftermath of trauma, emotional numbing has become a core defining
      feature of posttraumatic stress disorder (PTSD). METHOD: This paper seeks to
      briefly review the literature bearing on these seemingly disparate emotional
      responses to trauma as well as theoretical accounts of emotional numbing that
      have been proffered to date. We then offer an alternative theory of post
      traumatic emotional functioning and review empirical support for this model.
      RESULT: The experience of trauma produces very intense emotions such as
      overwhelming fear, horror, and anxiety, and these reactions can linger for a
      lifetime. Many trauma survivors also report restrictions in their emotional
      experience - a phenomenon most commonly referred to as emotional numbing. In
      contrast to previous accounts of posttraumatic emotional functioning our model
      posits that individuals with PTSD have difficulty expressing positive emotions as
      a result of re-experiencing states. We further argue that patients with PTSD are
      capable of experiencing and expressing the full range of emotions that were
      available pretraumatically. CONCLUSION: Our model holds that individuals with
      PTSD are not, in fact, 'emotionally numb' as a result of traumatic experience.
      Rather, PTSD is associated with hyperresponsivity to negatively valenced
      emotional stimuli. Consequently, patients with PTSD require more intense positive
      stimulation to access the full complement of appetitive or pleasant emotional
      behaviour.

PMID- 11982541
TI  - Delayed-onset posttraumatic stress disorder: a prospective evaluation.
AB  - OBJECTIVE: Delayed onset posttraumatic stress disorder (PTSD) refers to PTSD that
      develops at least 6 months after the traumatic event. This study aimed to index
      the features of patients who develop delayed-onset PTSD. METHOD: This study
      investigated delayed onset PTSD by prospectively assessing 103 motor vehicle
      accident survivors within 1 month of the motor vehicle accident for acute stress
      disorder, and subsequently assessing them for PTSD 6 months post-accident, and 2
      years post-accident. Patients were initially assessed for symptoms of traumatic
      stress, anxiety, depression, and resting heart rate. RESULTS: Five patients
      displayed PTSD 2 years post-trauma without meeting PTSD criteria 6 months
      posttrauma. Delayed onset cases were characterized by elevated psycho-pathology
      scores and resting heart rate levels within the initial month and elevated
      psychopathology 6 months posttrauma. CONCLUSIONS: These findings suggest that
      cases of delayed onset PTSD suffer subsyndromal levels of posttraumatic stress
      prior to the diagnosis of PTSD. These findings challenge the notion of PTSD
      developing after a period without symptoms.

PMID- 11982542
TI  - Psychiatry and the need for mental health care in Australia: findings from the
      National Survey of Mental Health and Wellbeing.
AB  - OBJECTIVE: This paper describes the pattern of consultations reported with
      psychiatrists and primary mental health care providers in the Australian adult
      population. It explores whether inequalities found in utilization of psychiatric
      services according to area are different in degree from inequalities in
      utilization of medical and surgical specialists,and describes the meeting of
      perceived needs for mental health care within those seen by psychiatrists.
      METHOD: The National Survey of Mental Health and Wellbeing (NSMHW) was a
      community survey employing clustered probability sampling, with a computerized
      field questionnaire which included sections of the composite international
      diagnostic interview (CIDI), as well as self-reported service utilization and
      perceived needs for care. RESULTS: By survey estimates, 1.8% of the Australian
      population consulted a psychiatrist in the last year. Among people with an ICD 10
      diagnosed mental disorder, 7.3% consulted a psychiatrist. Only about one in five
      people seen by a psychiatrist report the psychiatrist as the only mental health
      care provider. Disadvantaged areas of the cities and remote areas, when compared
      with the least deprived areas of the cities, showed lower rates of utilization.
      This effect is stronger in psychiatry than in other specialties. Patients seeing
      psychiatrists seem to be a more satisfied group than those seeing only other
      providers; nonetheless, some needs are not well met, and the role of the
      psychiatrist cannot be isolated as the cause of this satisfaction. CONCLUSIONS:
      Most care delivered by psychiatrists is de facto shared care. Psychiatrists as
      clinical professionals need to be continually mindful of the need to communicate
      with others providing care. Psychiatric services in Australia are not delivered
      in an equitable manner,and the inequalities are greater for psychiatric services
      than for other medical specialties.

PMID- 11982543
TI  - Distributing mental health care resources: strategic implications from the
      National Survey of Mental Health and Wellbeing.
AB  - OBJECTIVE: This paper considers mental health services resource distribution
      under the Australian second national mental health plan, with its direction to
      mental health services to be more inclusive of people with higher prevalence
      psychiatric disorders. We consider inequalities in mental health in Australia,and
      describe the performance of the composite census variable employed in the
      Victorian mental health funding distribution formula, the index of relative
      socioeconomic disadvantage (IRSED), in predicting disorder rates and perceived
      needs for care. METHOD: We review data sets generated through the National Survey
      of Mental Health and Wellbeing (NSMHWB) for their utility in development of
      resource distribution formulae. We present analyses from the 10 641 cases
      examined in the household survey to explore the role of the IRSED in predicting
      prevalence rates of anxiety, affective, substance misuse and other disorders,as
      well as perceived need for care. RESULTS: Recent epidemiological studies provide
      some additional sources of data to guide resource distribution,although the
      available data sets are found not to be optimized for examination of this issue.
      Greater levels of socioeconomic disadvantage of areas are associated with
      increased rates of morbidity in metropolitan areas, with different patterns for
      different disorder groups. The influence of the IRSED is more complex outside the
      major cities. CONCLUSIONS: The descriptive epidemiological data now available,
      despite significant investment, are relatively crude instruments for this current
      purpose. The findings support the case for using the IRSED as a proxy indicator
      for morbidity for the high prevalence disorders, but only within metropolitan
      areas. This examination confirms the existence of significant inequalities in
      mental health between Australian urban areas with different socioeconomic
      characteristics.

PMID- 11982544
TI  - Naltrexone in the treatment of heroin dependence: relationship with depression
      and risk of overdose.
AB  - OBJECTIVE: This article examines the use of naltrexone in the treatment of heroin
      dependence. The relationship between naltrexone and depression as well as risk of
      overdose is examined. METHOD: The existing literature is reviewed along with
      recent interim data from clinical trials underway in Victoria. RESULTS:
      Naltrexone is a recent addition to treatment for heroin dependence in Australia.
      The relationship between depression and naltrexone has been examined in previous
      literature. Underlying rates of depression in heroin users are high and treatment
      may resolve or exacerbate depression. Research to date demonstrates that the
      addition of naltrexone does not necessarily increase depression in patients. The
      risk of non-fatal heroin overdose is significantly elevated after naltrexone
      treatment as a result of reduced tolerance. Data from clinical trials underway in
      Victoria demonstrate a significantly elevated rate of non-fatal overdose in
      naltrexone patients compared to those in substitution maintenance treatment. The
      mortality rate subsequent to naltrexone treatment appears to be equivalent to or
      greater than that for untreated heroin users. Further research is required.
      CONCLUSIONS: Clinicians need to carefully monitor depression in patients, and
      warn patients of the risks of reduced tolerance to opiates following naltrexone
      treatment. Agonist treatments such as methadone, LAAM and buprenorphine carry
      much less risk of overdose.

PMID- 11982545
TI  - Changes in the rate of diagnosis of major depression in adolescents following
      routine use of a depression rating scale.
AB  - OBJECTIVE: Because major depression in adolescents often goes undiagnosed, it is
      useful to establish whether clinicians' rates of making this diagnosis in a
      specialist adolescent mental health service change when a self-rating depression
      scale is routinely administered. METHOD: A retrospective, naturalistic study
      examining the rate of diagnosis of major depression in a mental health service
      between 1993 and 1997. The intervention was the administration of the Center for
      Epidemiological Studies Depression Scale (CES-D)prior to initial assessment from
      September 1995 onwards. The proportion of clinical diagnoses of DSM-III-R or DSM
      IV major depression was the outcome measure. Age, gender, ratings of depression
      and other confounding variables were used to control for changes in patient
      population over time. RESULTS: One thousand three hundred and ten adolescents
      aged 12 to 17 years assessed between 1993 and 1997 were included. After taking
      into account potential confounders, diagnosis of major depression was 2.8 times
      (95% confidence interval 1.8, 4.3) as likely when the CES-D was in use. Increase
      was more marked when adolescents were more disturbed overall. There was no
      evidence suggesting this was due to changes in diagnostic practices or in the
      patient population. CONCLUSION: Availability to clinicians of a self-rating
      depression scale completed prior to assessment was associated with an increase in
      the frequency of diagnosis of depression in a specialist mental health service
      for adolescents.

PMID- 11982546
TI  - Characteristics of parent- and child-reported anxiety in psychostimulant
      medication naive, clinically referred children with attention deficit
      hyperactivity disorder, combined type (ADHD-CT).
AB  - OBJECTIVE: Anxiety is a frequent comorbid condition in referred primary school
      age children with attention deficit hyperactivity disorder, combined type (ADHD
      CT), yet there has been relatively little systematic research of the nature of
      this comorbid anxiety. We describe the characteristics of parent-reported child
      anxiety disorders and child-reported anxiety disorders in primary school-age
      children with ADHD-CT. METHOD: A cross-sectional study of 75 clinically-referred
      psychostimulant medication naive children with ADHD-CT examining separately
      parent and child reports of anxiety, defined categorically and dimensionally. A
      two-year follow up of 12 children with parent-reported child anxiety and 12
      children with child-reported anxiety was also completed. RESULTS: There was no
      significant association between the child and parent reports of anxiety.
      Generalized anxiety disorder (GAD), separation anxiety disorder (SAD), specific
      phobia (SpPh) and social phobia (SoPh) were the most common anxiety disorder
      diagnoses reported by parents and children. Two-year follow-up data revealed no
      decrease in the parent report but a significant decrease in the child report of
      anxiety disorders. CONCLUSIONS: The dissonance between the parent report of child
      anxiety and the child report of anxiety, emphasizes the importance of careful and
      thorough clinical assessment of the child's perspective. The nature of parent
      reported child anxiety and children's self-report of anxiety requires further
      systematic research.

PMID- 11982547
TI  - Treatments for chronic fatigue syndrome and the Internet: a systematic survey of
      what your patients are reading.
AB  - OBJECTIVE: To evaluate the type, quality, and focus of patient information on the
      treatment of chronic fatigue syndrome on the Internet using simple search
      techniques. DESIGN: The search phrase 'chronic fatigue syndrome' was entered into
      nine common Internet search engines. The 25 most highly ranked pages identified
      by each of the nine search engines were analysed using a standardized pro forma.
      The following outcome measures were used: balance of content, consistency of
      content with evidence-based practice, declared authorship with credentials,
      information sources including the presence of references, the declaration of any
      potential conflict of interest, and the need to clarify information with an
      appropriate health professional. RESULTS: Two hundred and twenty-five websites
      were reviewed during a 2-week period in September 2000. A further 15 sites (6.3%)
      were inaccessible. Agreement between websites and systematic reviews of treatment
      for chronic fatigue syndrome ranged from 4 to 68%, the greatest agreement being
      for recommendations for graded exercise and the avoidance of prolonged rest. Most
      sites (64%) had a named author. Only a quarter to a third contained a declaration
      of interest, advised readers to clarify information with an appropriate health
      professional, or avoided inaccurate statements. CONCLUSIONS: The Internet
      contains a great deal of information on chronic fatigue syndrome that is neither
      balanced nor consistent with evidence-based practice. Doctors individually, and
      as a profession, should provide guidance on which Internet sites to trust.

PMID- 11982548
TI  - Diagnostic efficiency of the Hospital Anxiety and Depression Scale in women with
      early stage breast cancer.
AB  - OBJECTIVE: To investigate the diagnostic efficiency of the Hospital Anxiety and
      Depression Scale (HADS) inpatients with breast cancer. METHODS: Women (303)
      recently diagnosed with stage I or II breast cancer completed the HADS and were
      psychiatrically assessed. Recommended cut-off scores for Depression (D) and
      Anxiety(A) Scales identified probable caseness and the accuracy was compared with
      DSM-IV diagnoses. Cut-off scores were varied to establish optimal accuracy.
      RESULTS: One hundred and eleven (36.6%)met criteria for depressive disorders and
      25 (8.3%) met criteria for anxiety disorders. At the recommended cut-off score of
      11 for the D scale, positive and negative predictive values were.75 and.64,
      respectively, while sensitivity and specificity were.05 and.99, respectively. For
      the A scale, positive predictive value(PPV) was.15; negative predictive value
      (NPV),.90; sensitivity,.08; and specificity,.87. Reducing the cut-off score to 5
      produced PPV of.63, NPV of.74, sensitivity of.49 and specificity of .83 for the D
      scale;.14,.94,.75 and.45, respectively, for the A scale. Composite scores (cut
      off of 22) had a PPV of.92, NPV of.57, sensitivity of.09 and specificity of.99.
      CONCLUSIONS: Recommended cut-off scores for the HADS may result in under
      reporting of psychiatric morbidity among women with early stage breast cancer.
      These results are consistent with other recent studies of the HADS. The type of
      constructs measured by the scale is the likely explanation for its limited
      utility when screening for psychiatric morbidity in early stage breast cancer.

PMID- 11982549
TI  - The written report in consultation-liaison psychiatry: a proposed schema.
AB  - OBJECTIVE: The consultation-liaison psychiatry (CLP) written report serves
      several crucial functions; it therefore needs to be presented in a meaningful
      format to its readers. Surprisingly little has been written about its optimal
      nature. Our aim is to offer a schema which promotes effective communication.
      METHODS: We have reviewed pertinent literature, consulted with CLP colleagues and
      convened a focus group that a number of them attended. RESULTS: The core
      functions of the CLP report are to offer the referrer (and other relevant
      professionals) key comprehensible findings, recommendations for treatment and
      advice for follow up. Additional purposes are educational, archival and medico
      legal. Our schema contains eight sections: Who is the patient? Why you referred
      the patient to us at this particular time? What did we find? Who are the
      patient's family and other supports? How do we understand these findings? What do
      we recommend regarding management? What further clinical developments have
      ensued? and What do we recommend regarding psychosocial follow-up? We provide
      guidelines concerning the content of each section and illustrate the use of the
      schema with two clinical cases. CONCLUSIONS: The functions of the CLP report are
      not satisfied through conventional psychiatric-history note taking. Our related
      yet different framework is inclined to be a more effective means to convey
      necessary clinical data and treatment recommendations.

PMID- 11982550
TI  - Successful treatment of behavioural problems in dementia using a cholinesterase
      inhibitor: the ethical questions.
AB  - OBJECTIVE: To review the effect of cholinesterase inhibitors on the behavioural
      and neuropsychiatric symptoms of dementia and discuss the current clinical
      guidelines for the prescription of cholinesterase inhibitors in Australia.
      METHOD: This paper reports the case of a patient with clinical diagnosis of
      dementia with lewy bodies (DLB) who was referred to an old age psychiatry service
      for the treatment of severe visual hallucinations and behavioural problems.
      RESULTS: Pharmacological treatment with olanzapine produced marked parkinsonism,
      agitation and confusion. A cholinesterase inhibitor, donepezil, was introduced.
      The introduction of donepezil was associated with cognitive improvement (mini
      mental state examination [MMSE] increased from 23 to 27) and complete remission
      of behavioural symptoms. CONCLUSION: That cholinesterase inhibitors may have a
      role in the management of behavioural symptoms of dementia and the current
      Australian PBS guidelines for prescribing cholinesterase inhibitors are
      clinically restrictive. This has clinical and ethical implications that need to
      be addressed by consumers, the medical community and regulating authorities.

PMID- 11982551
TI  - Treatment-resistant depression: when antidepressant drug intolerance may indicate
      food intolerance.
AB  - OBJECTIVE: To describe a patient with food intolerance probably contributing to
      depressive symptoms, intolerance to psychotropic medication and treatment
      resistance. METHOD: The case vignette and investigatory procedures are detailed.
      RESULTS: The patient's course improved considerably with an elimination diet.
      CONCLUSIONS: The prevalence of food intolerance as a contributing factor to
      depressive disorders requires clarification. Clinicians should be aware of the
      possible syndrome and that it may be worsened by psychotropic medication.

PMID- 11982552
TI  - Medicine, psychiatry and euthanasia: an argument against mandatory psychiatric
      review.

PMID- 11982553
TI  - Persisting continuous visual perception disorder in a chronic MDMA ('ecstasy')
      user.

PMID- 11982554
TI  - Responsible regulation of psychiatric practice.

PMID- 11982555
TI  - Cerebellar ataxia with intravenous valproate and haloperidol.

PMID- 11982556
TI  - Polydipsia and risperidone.

PMID- 11982557
TI  - Doubts about HoNOS.

PMID- 11982558
TI  - Weight gain and hyperglycaemia associated with olanzapine.

PMID- 11982559
TI  - Outcome measures used by the Mental Health Review Board.

PMID- 11982561
TI  - Cognitive therapy of depression. Aaron T Beck, A John Rush, Brian F Shaw, Gary
      Emery. New York: Guilford Press, 1979.

PMID- 11982560
TI  - Cognitive therapy of depression. Aaon Beck, John Rush, Brian Shaw, Gary Emery.
      New York: Guilford, 1979.

PMID- 11982563
TI  - Diseases of the generative nail apparatus. Part I: Nail matrix.
AB  - Disorders of the generative structures of the nail produce a characteristic set
      of outcomes. The matrix is the seat of nail development and diseases or insults
      of this germinative epithelium will tell a story in the signs that unfold in the
      ensuing nail growth. This story will be influenced by the intensity, duration and
      extent of this pathology. A method of categorizing changes associated with the
      generative matrix of the nail will be presented.

PMID- 11982564
TI  - Atypical lentiginous junctional naevi of the elderly and melanoma.
AB  - The diagnosis of atypical lentiginous melanocytic naevi in chronic sun-damaged
      skin is a clinical and pathological challenge. Mottled skin in the elderly is a
      result of extensive freckling, guttate hypomelanosis, solar lentigines,
      seborrhoeic keratoses and small dark lentigines. In addition, atypical
      lentiginous junctional naevi may be seen as isolated lesions and may merge with
      lesions that are indistinguishable from lentigo maligna. The predominant site
      distribution of such lesions on the trunk and limbs and the presence of a nested
      naevoid pattern on biopsy differs from classical lentigo maligna, which develops
      mainly on the head and neck. Based on case studies combining dermatoscopy with
      clinical and pathological features, we have found that atypical lentiginous
      junctional naevi of the elderly may evolve to lentigo maligna and in some cases
      to small cell (naevoid) melanomas. Such lesions have been previously classified
      as dysplastic naevi, atypical melanocytic hyperplasia, atypical melanocytic
      proliferation, atypical lentiginous melanocytic proliferation or premalignant
      melanosis (McGovern). The current definition of lentigo maligna appears too
      narrow and the pathway to lentigo maligna in the elderly skin may include a
      naevoid subset.

PMID- 11982565
TI  - Scrubbing for cutaneous procedures can be hazardous.
AB  - Office-based minor cutaneous surgery is a service provided by many medical
      practitioners. In New South Wales, Australia, it is a legal requirement for
      practitioners to surgically scrub before donning sterile gloves for all forms of
      invasive surgery, including minor cutaneous procedures. Frequent scrubbing causes
      altered skin barrier function, irritant dermatitis and a potential risk of latex
      sensitization. These adverse effects are associated with significant morbidity
      and cost. Better tolerated alternatives, including alcohol-based hand rubs,
      should be considered in preference to traditional surgical scrubs in order to
      reduce these occupational risks for minor proceduralists. Well-controlled,
      prospective studies should explore what extent of hand washing is necessary for
      donning sterile gloves for minor cutaneous surgery.

PMID- 11982566
TI  - Onychomycosis of toenails: orthopaedic and podiatric considerations.
AB  - Onychomycosis is common, affecting approximately 5% of the population, and is the
      most resistant form of superficial fungal infection. Dermatologists often view
      the nail apparatus in static terms and unfortunately give little consideration to
      the functional aspects of the digit. In the case of toenails, it is important to
      consider the toes and foot as a closely integrated functional unit. It is
      essential that in any case of onychomycosis or onychodystrophy that, as
      clinicians, we have an understanding of foot dynamics, of structure/function
      relationships and of the implications of orthopaedic/podiatric factors when
      evaluating cases of nail dystrophy. When confronted with cases of possible
      onychomycosis, we must adopt a systematic and sometimes multidisciplinary
      approach in the evaluation and management of these patients to improve patient
      outcomes.

PMID- 11982567
TI  - Ultrastructural immunocytochemistry of autoimmune bullous diseases.
AB  - Advanced immunopathological assays have been developed to elucidate the
      pathophysiology and provide more precise nosological definitions of the
      immunobullous diseases. Forty-seven patients suffering from autoimmune bullous
      diseases (intra- or subepidermal) were studied by immunoelectron microscopy
      (direct and indirect). Peroxidase staining was revealed by diaminobenzidine
      (determination of immune deposit location) in the majority of the cases of
      subepidermal bullous diseases, but in less than half of the cases of
      intraepidermal bullous diseases. Immunoelectron microscopy features contributed
      in verifying the diagnosis of rare entities such as cicatricial pemphigoid,
      paraneoplastic autoimmune bullous disease, linear IgA disease and epidermolysis
      bullosa acquisita.

PMID- 11982568
TI  - Loose anagen syndrome: a prospective study of three families.
AB  - Loose anagen syndrome (LAS) is an autosomal dominant, age-related disorder
      characterized by the ability to easily and painlessly extract unsheathed anagen
      hairs from the scalp with a gentle hair pull. The phenotype is heterogeneous with
      three distinct clinical presentations. To further characterize the phenotype of
      loose anagen syndrome and its fluctuations over time, a prospective study of
      eight cases from three families was conducted over a period of 18 months.
      Patients were examined using standardized hair-pull and hair-pluck protocols.
      Each of the three different phenotypes of LAS were found to be present in one
      family. This implies that these phenotypes are variants of a single genotype,
      modified by environmental or age-related factors. The hair-pluck trichogram from
      LAS cases consistently showed a high proportion of loose anagen (LA) hairs. In
      contrast the hair-pull test was found to vary over time with regards to the
      number of LA hairs that could be extracted. Periods where no hairs could be
      obtained on hair pull were found. These findings have important implications in
      the diagnosis of LAS. A single negative hair-pull test does not exclude the
      diagnosis. If LAS is suspected on clinical grounds, then either a hair-pluck
      trichogram or serial re-examination by hair pull would be required to exclude the
      diagnosis.

PMID- 11982569
TI  - Clinical improvement and significant reduction of total serum IgE in patients
      suffering from severe atopic dermatitis treated with oral azathioprine.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease: the incidence is
      increasing in many countries and treatment can be difficult. The aim of this
      retrospective case series was to examine the effect of oral azathioprine on the
      clinical severity and serum IgE levels in 38 patients with severe atopic
      dermatitis. The AD was well-controlled in nearly 80% (30/38). The maintenance
      dose required was in the range 25-200 mg per day. Four patients withdrew because
      of adverse affects, including one case of pancytopenia, and a further four ceased
      azathioprine after 4 months because of a lack of clinical improvement. Total
      serum IgE levels were measured before commencing azathioprine and after two years
      of treatment in 26 patients. IgE levels decreased in almost all patients and this
      was statistically significant (P = 0.012).

PMID- 11982570
TI  - Actinic prurigo: a retrospective analysis of 21 cases referred to an Australian
      photobiology clinic.
AB  - Actinic prurigo (AP) is a rare acquired idiopathic photodermatosis, reported most
      often in American Indians, but also in Caucasian and Asian populations. The skin
      lesions in AP predominantly affect exposed sites but may involve covered areas,
      and often result in postinflammatory scarring. The diagnosis of AP can be
      difficult and relies on a combination of history, clinical experience and
      investigations including phototesting and human leucocyte antigen typing. Twenty
      one patients (17 women, four men) diagnosed with AP at the photobiology clinic at
      St Vincent's Hospital Melbourne were reviewed in this retrospective study. The
      mean age of patients at presentation to the clinic was 25 years, with the mean
      age of onset being 14 years. Phototesting was undertaken in 20 patients, with 12
      (60%) having reduced and eight (40%) normal minimal erythema doses. Human
      leucocyte antigen typing indicated 18 patients (85.7%) were DR4 positive, with
      further subtyping of the DR4 allele establishing that 15 patients (71.4%) were
      DRB1*0407 positive and that two (9.5%) were DRB1*0401 positive. This condition is
      often recalcitrant, with treatment options including photoprotection, topical and
      oral corticosteroids, antimalarials, phototherapy and thalidomide.

PMID- 11982571
TI  - Photosensitive dermatitis due to sunscreen allergy in a child.
AB  - We report a case of photoallergic contact dermatitis to two sunscreen agents,
      methoxycinnamate and oxybenzone, occurring in a 6-year-old Asian boy.

PMID- 11982572
TI  - Multicentric reticulohistiocytosis presenting with a rash and arthralgia.
AB  - A case of multicentric reticulohistiocytosis in a 53-year-old woman with a
      history of generalized cutaneous eruptions followed by arthralgia is presented. A
      thorough malignancy screen was performed with negative results. Treatment was
      commenced with oral prednisone 20 mg daily, which rapidly resulted in marked
      improvement of joint symptoms and resolution of self-perceived functional
      disability. As there was little improvement of her rash, oral azathioprine was
      added at 100 mg daily. Both drugs were well-tolerated and the patient was
      discharged from hospital on these medications. Two months later the azathioprine
      was reduced to 50 mg per day orally, following a small rise in hepatic
      transaminases. Within 4 months there had been dramatic improvement in the rash
      and cutaneous nodules with complete remission of the arthralgia and pruritus.
      During this time the oral prednisone had gradually been decreased to 10 mg daily.
      To date only the periungual nodules persist.

PMID- 11982573
TI  - Allopurinol-induced pustular eruption: an unusually mild case.
AB  - Pustular drug eruptions are uncommon and usually present with an acute illness. A
      75-year-old-woman presented with a widespread pruritic pustular erythematous skin
      rash. She was otherwise well and had been commenced on allopurinol for gout 3
      weeks before developing the rash. A skin biopsy was consistent with a pustular
      drug eruption, with features of acute generalized exanthematous pustulosis
      (AGEP). Allopurinol was the probable causative agent and withdrawal resulted in
      resolution of her eruption within 6 weeks. A diagnosis of AGEP was considered;
      however, this patient did not fulfil the diagnostic criteria.

PMID- 11982574
TI  - Myeloma-associated systemic amyloidosis presenting with acquired digital cutis
      laxa-like changes.
AB  - A 59-year-old woman presented with a 6-year history of lax skin on the distal
      fingers of both hands, as well as a recent increase in the size of her tongue.
      Histopathology of skin from her distal finger showed amyloid deposition and bone
      marrow biopsy revealed an underlying plasma cell dyscrasia. Initial treatment
      with cyclophosphamide, vincristine, adriamycin and methylprednisolone has
      produced a significant reduction in the swelling of both her hands and tongue.
      Acquired digital cutis laxa-like changes are a rare cutaneous manifestation of
      systemic amyloidosis.

PMID- 11982575
TI  - Clinical and histological spectrum of elastotic changes induced by penicillamine.
AB  - A 79-year-old-man with cystinuria requiring long-term penicillamine therapy
      presented with a 6-month history of itchy annular lesions in both axillae.
      Clinical examination revealed lesions consisting of crusted keratotic papules
      coalescing in an annular distribution. Associated findings included generalized
      skin laxity accentuated on the upper trunk and arms, as well as small yellowish
      papules on the neck. Histological evaluation revealed short, thick, eosinophilic
      elastic fibres with nodular protrusions. Transepidermal elimination of abnormal
      elastic fibres was also evident. We discuss the histological and clinical
      spectrum of penicillamine-induced elastotic changes and compare these changes to
      those seen in primary elastotic disorders.

PMID- 11982576
TI  - Immediate-type latex hypersensitivity in a hairdresser.
AB  - Hairdressers commonly develop contact dermatitis caused by either skin irritants
      or allergens to which they are exposed. Those using latex gloves are also at risk
      of developing immediate hypersensitivity reactions to latex. We present a
      hairdresser with hand dermatitis, primarily as a result of immediate-type
      hypersensitivity to latex causing contact urticaria, diagnosed with
      radioallergosorbent testing. Only three previous studies have reported latex
      allergy in hairdressers. This condition needs to be considered as a differential
      diagnosis in hairdressers presenting with hand dermatitis and a history of
      wearing either rubber or disposable latex gloves.

PMID- 11982577
TI  - Sporadic case of ichthyosis bullosa of Siemens.

PMID- 11982578
TI  - Sensitivity to UV-cured inks used in bank notes.

PMID- 11982579
TI  - Persistent head lice following multiple treatments.

PMID- 11982581
TI  - Keratoacanthoma with perineural invasion.

PMID- 11982583
TI  - Down-regulation of Th1 responses in human neonates.

PMID- 11982584
TI  - Takes your breath away--the immunology of allergic alveolitis.
AB  - Extrinsic allergic alveolitis (synonym: hypersensitivity pneumonitis) is caused
      by inhaling antigenic aerosols which induce hypersensitivity responses in
      susceptible individuals. It is an interstitial inflammatory disease affecting the
      distal, gas-exchanging parts of the lung, in contrast to allergic asthma where
      the inflammation is more proximal, affecting the conducting airways. The aims of
      this review are to describe current concepts of the immunology of this model of
      lung inflammation, to describe some of the constitutional and environmental
      characteristics which affect disease susceptibility and development, and to
      describe topics for prospective study.

PMID- 11982585
TI  - The strength of B cell immunity in female rhesus macaques is controlled by CD8+ T
      cells under the influence of ovarian steroid hormones.
AB  - To understand more clearly how mucosal and systemic immunity is regulated by
      ovarian steroid hormones during the menstrual cycle, we evaluated the frequency
      of immunoglobulin- and antibody-secreting cells (ISC, AbSC) in genital tract and
      systemic lymphoid tissues of normal cycling female rhesus macaques. The frequency
      of ISC and AbSC was significantly higher in tissues collected from animals in the
      periovulatory period of the menstrual cycle than in tissues collected from
      animals at other stages of the cycle. The observed changes were not due to
      changes in the relative frequency of lymphocyte subsets and B cells in tissues,
      as these did not change during the menstrual cycle. In vitro, progesterone had a
      dose-dependent inhibitory effect, and oestrogen had a dose-dependent stimulatory
      effect on the frequency of ISC in peripheral blood mononuclear cell (PBMC)
      cultures. The in vitro effect of progesterone and oestrogen on ISC frequency
      could not be produced by incubating enriched B cells alone with hormone, but
      required the presence of CD8+ T cells. Following oestrogen stimulation, a CD8+
      enriched cell population expressed high levels of IFN-gamma and IL-12. The
      changes in B cell Ig secretory activity that we document in the tissues of female
      rhesus macaques during the menstrual cycle is due apparently to the action of
      ovarian steroid hormones on CD8+ T cells. Thus, CD8+ T cells control B cell
      secretory activity in both mucosal and systemic immune compartments.
      Understanding, and eventually manipulating, the CD8+ regulatory cell-B cell
      interactions in females may produce novel therapeutic approaches for autoimmune
      diseases and new vaccine strategies to prevent sexually transmitted diseases.

PMID- 11982586
TI  - Leptin inhibits stress-induced apoptosis of T lymphocytes.
AB  - Leptin, which is secreted by adipocytes, the placenta and the stomach, not only
      controls appetite through leptin receptors in the hypothalamus but also regulates
      cell-mediated immunity. In this study we have demonstrated that continuous
      injection of leptin prevents the reduction in lymphocyte numbers normally
      observed in fasted and steroid-injected mice. Consistent with leptin-induced
      protection, we observed up-regulation of the bcl-xL gene as a result of signal
      transduction via leptin receptors on lymphocytes. We suggest that leptin might
      contribute to the recovery of immune suppression in malnourished mice by
      inhibiting lymphocyte apoptosis.

PMID- 11982587
TI  - Ganglioside expression in tissues of mice lacking beta2-microglobulin.
AB  - This study presents a comparative analysis of gangliosides from lymphoid (spleen
      and thymus) and other (brain, liver, lungs and muscle) tissues of C57BL/6 mice
      lacking the gene for beta2-microglobulin (beta2M), a constitutive component of
      the MHC class I molecule. Ganglioside fractions in the tissues of mice homozygous
      (beta2M-/-) and heterozygous (beta2M-/+) for the gene deletion were determined by
      high performance thin-layer chromatography (HPTLC), followed by immunostaining
      with specific polyclonal antibodies. Ubiquitous gangliosides GM3(Neu5Ac) and
      GM3(Neu5Gc) were the dominant gangliosides in the lungs of the control beta2M-/+
      mice, whereas the homozygous knockout mice had substantially decreased expression
      of these structures. The lungs of the beta2M-/- mice also had reduced expression
      of T-lymphocyte-specific GM1b-type gangliosides (GM1b and GalNAc-GM1b). beta2M
      deficient mice also had more GM1a and GD1a gangliosides in the liver, and several
      neolacto-series gangliosides were increased in the brain and lungs. This study
      provides in vivo evidence that the beta2M molecule can influence the acquisition
      of a distinct ganglioside assembly in different mouse organs, implicating its non
      immunological functions.

PMID- 11982588
TI  - Interleukin-10 inhibits experimental mesangial proliferative glomerulonephritis.
AB  - Conflicting reports exist regarding the effects of interleukin-10 (IL-10) on
      mesangial cells. There have been reports of both proliferative and
      antiproliferative effects, and both proinflammatory and anti-inflammatory effects
      of IL-10 on mesangial cells. However, the potential for IL-10 to affect
      glomerulonephritis characterized by mesangial proliferation is not known. To test
      the hypothesis that IL-10 would limit experimental mesangial proliferative
      glomerulonephritis, IL-10 was administered to rats in which mesangial
      proliferative glomerulonephritis was induced by administration of anti-Thy 1
      antibody. Compared to control treated rats, IL-10 treated rats showed less
      proliferation, with fewer cells in glomeruli. Glomerular cellular proliferation
      was reduced, assessed by the numbers of cells within glomeruli expressing either
      proliferating cell nuclear antigen (PCNA) or bromodeoxyuridine. Glomerular
      macrophage influx (but not the proportion of glomerular macrophages that were
      PCNA positive) was reduced by IL-10 administration. There was no significant
      reduction in glomerular alpha-smooth muscle actin staining. IL-10 treatment
      resulted in reduced renal IL-1beta mRNA expression and reduced glomerular ICAM-1
      expression, but renal expression of MCP-1 and osteopontin mRNA was unaltered.
      This study demonstrates that in experimental mesangial proliferative
      glomerulonephritis IL-10 diminishes inflammatory cell recruitment and mesangial
      cell proliferation. The effects of IL-10 in inhibiting mesangial cell
      proliferation are likely to be due to a combination of direct effects of IL-10 on
      mesangial cells and effects mediated by macrophages.

PMID- 11982589
TI  - Vascular cell adhesion molecule-1 (VCAM-1) blockade in collagen-induced arthritis
      reduces joint involvement and alters B cell trafficking.
AB  - Vascular cell adhesion molecule-1 (VCAM-1 or CD106) is important in leucocyte
      trafficking and its increased expression is associated with a number of chronic
      inflammatory diseases, including rheumatoid arthritis (RA). We used a
      neutralizing monoclonal antibody (M/K-2.7) to investigate the role of VCAM-1 in
      collagen-induced arthritis (CIA), an autoimmune model of RA. A single injection
      of M/K-2.7 (0.5 mg) into naive mice caused leucocytosis within 20 h, due to
      increased numbers of circulating B cells and macrophages, as well as neutrophils.
      The most marked effect was on the numbers of immature B cells (B220loIgM+) which
      were increased approximately fourfold. CIA was elicited in DBA/1 mice by
      immunization with chick type II collagen (CII) in Freund's complete adjuvant,
      followed by a repeat injection 21 days later. Repeated M/K-2.7 administration
      from the time of primary CII immunization reduced the clinical severity, but not
      the incidence, of CIA compared to isotype-control monoclonal antibody-treated
      mice. Histological assessment showed fewer arthritic joints in M/K-2.7-treated
      mice; however, affected joints showed the same range of severity as those of
      control mice. Anti-CII IgG1 levels were reduced in anti-VCAM-1-treated mice but
      the cellular immune response to CII was unaffected. In contrast, VCAM-1 blockade
      from the onset of clinical features of CIA did not prevent disease progression.
      These results establish a role for VCAM-1 in promoting polyarticular involvement
      in CIA, most probably via an effect on B cells.

PMID- 11982590
TI  - Prostaglandin E2 down-regulates viable Bacille Calmette-Guerin-induced macrophage
      cytotoxicity against murine bladder cancer cell MBT-2 in vitro.
AB  - The regulatory effect of prostaglandin (PG) E2 and a cyclooxygenase (COX)
      inhibitor on Bacille Calmette-Guerin (BCG)-induced macrophage cytotoxicity in a
      bladder cancer cell, MBT-2, was studied in vitro. BCG stimulated thioglycollate
      elicited murine peritoneal exudate cells (PEC) to induce cytotoxic activity and
      to produce cytokines such as interferon (IFN)-gamma, tumour necrosis factor (TNF)
      alpha and PGE2. NS398, a specific COX-2 inhibitor, and indomethacin (IM), a COX-1
      and COX-2 inhibitor, enhanced viable BCG-induced cytotoxic activity and IFN-gamma
      and TNF-alpha production of PEC. However, NS398 and IM did not enhance these
      activities induced by killed BCG. Enhanced cytotoxicity was mediated by increased
      amounts of IFN-gamma and TNF-alpha. Exogenous PGE2 reduced cytotoxic activity and
      IFN-gamma and TNF-alpha production of PEC. These results suggest that PGE2
      produced by BCG-activated macrophages has a negative regulatory effect on the
      cytotoxic activity of macrophages. Accordingly, a PG synthesis inhibitor may be a
      useful agent to enhance BCG-induced antitumour activity of macrophages.

PMID- 11982591
TI  - Activated macrophages for treating skin ulceration: gene expression in human
      monocytes after hypo-osmotic shock.
AB  - Macrophages play a major role in almost all stages of the complex process of
      wound healing. It has been previously shown that the incorporation of a hypo
      osmotic shock step, in the process of monocyte-concentrate preparation from a
      blood unit, induces monocyte/macrophage activation. As the macrophages are
      produced using a unique, closed and sterile system, they are suitable for local
      application on ulcers in elderly and paraplegic patients. Enhanced phagocytosis
      by the activated cells, as well as increased secretion of cytokines such as IL-1,
      IL-6, were detected in a recent study which are in accord with the very
      encouraging clinical results. In the present study, we used DNA microarrays to
      analyse the differential gene expressions of the hypo-osmotic shock-activated
      monocytes/macrophages and compare them to non-treated cells. Of the genes that
      exhibited differences of expression in the activated cell population, 94% (68/72)
      displayed increased activity. The mRNA levels of 43/68 of these genes (63%) were
      found to be 1.5-fold or higher (1.5-7.98) in the activated macrophages cell
      population as compared to the non-treated cells. Only four genes were found to
      have lower mRNA levels in the activated cells, with ratios of expression of 0.62
      0.8, which may suggest that the changes are insignificant. A significant number
      of the genes that showed increased levels of expression is known to be directly
      involved in macrophage function and wound healing. This may correlate with the
      increased secretion of different cytokines by the activated macrophages depicted
      previously. Other groups of genes expressed are known to be involved in important
      pathways such as neuronal growth and function, developmental defects and cancer.
      The hypo-osmotic shock induces a gene expression profile of cytokines and
      receptors in the activated cells. These may evoke potential abilities to produce
      a variety of protein products needed in the wound healing process and may bring
      to light possibilities for other therapeutic applications of these cells.

PMID- 11982592
TI  - Penetration of engineered antibody fragments into the eye.
AB  - Antibodies are powerful immunotherapeutic agents but their use for treating
      ocular disorders is limited by their poor penetration into the eye. We
      hypothesized that antibody fragments of relatively small size might penetrate the
      cornea more readily. Monovalent single chain variable region (scFv) antibody
      fragments and divalent miniantibodies were engineered from existing monoclonal
      antibodies, expressed in a bacterial expression system, and purified by metal ion
      affinity chromatography. Corneoscleral preparations from normal pig and cat eyes
      were mounted in a corneal perfusion chamber. Intact antibodies and antibody
      fragments were applied topically to the anterior corneal surface over 12-h
      periods, and samples were collected from the artificial anterior chamber. Similar
      experiments were performed with whole enucleated pig and human eyes. Penetration
      of antibodies and fragments was quantified by high-sensitivity flow cytometry on
      appropriate target cells. Both monovalent scFv and divalent miniantibody
      fragments (but not whole immunoglobulin molecules) passed through de
      epithelialized and intact corneas after topical administration, and could be
      detected by antigen binding. Addition of 0.5% sodium caprate facilitated
      penetration through intact corneas. Topically-applied scFv was found to penetrate
      into the anterior chamber fluid of rabbit eyes in vivo. The engineered fragments
      were stable and resistant to ocular proteases. Monovalent and divalent antibody
      constructs of molecular weight 28 kD and 67 kD, respectively, can penetrate
      through intact corneas into the anterior chamber, with retention of appropriate
      antigen-binding activity. Such constructs may form novel therapeutic agents for
      topical ophthalmic use.

PMID- 11982593
TI  - Autoantibodies to human endogenous retrovirus-K are frequently detected in health
      and disease and react with multiple epitopes.
AB  - A number of studies have found increased levels of antibodies to human endogenous
      retroviruses (HERVs) in autoimmune rheumatic diseases. It is not clear whether
      this immune response is driven by the HERV itself or by cross-reactions with an
      exogenous virus or an autoantigen. To address this question, we examined the
      antibody response to the Env protein of two closely related members of the HERV-K
      family, HERV-K10 and IDDMK1,222. By immunoblotting of recombinant proteins,
      antibodies were found in 32-47% of 84 sera from patients with autoimmune
      rheumatic disease, and 29% of 35 normal controls. Epitope mapping with
      overlapping 15mers identified multiple reactive peptides on both antigens, with
      one (GKTCPKEIPKGSKNT) containing immunodominant epitope(s). By ELISA, the median
      titre of antibody to this peptide was significantly increased in 39 patients with
      SLE compared to 39 healthy controls and 86 patients with other rheumatic diseases
      (P < 0.003). We have shown that there is a high frequency of IgG antibodies to
      HERV-K env sequences in human sera, both in health and autoimmune rheumatic
      disease, and that the response is to multiple epitopes. This supports the
      hypothesis that the autoimmune response to HERV-K is antigen-driven and may be an
      early stage in the chain of events that leads to tolerance breakdown to other
      autoantigens.

PMID- 11982594
TI  - Analysis of mitochondrial antigens reveals inner membrane succinate dehydrogenase
      flavoprotein subunit as autoantigen to antibodies in anti-M7 sera.
AB  - The role of mitochondrial proteins as antigens to antibodies of anti-M7 sera was
      analysed by flavin fluorescence, one- and two-dimensional Western blots and blue
      native gel electrophoresis. Flavin fluorescence of succinate dehydrogenase
      (SucDH, complex II of the respiratory chain) of rat liver inner mitochondrial
      membranes correlated with the immunoreactivity of a representative anti-M7
      myocarditis serum. Antigens of isolated bovine heart mitochondria reacting with
      antibodies of myocarditis serum on two-dimensional Western blots were identified
      by MALDI-TOF and NanoESI mass spectrometry as myosin heavy chain beta and as
      dihydrolipoamide dehydrogenase of the mitochondrial 2-oxoacid dehydrogenase
      complexes. The SucDH-flavoprotein was not resolved as a discrete protein spot on
      two-dimensional polyacrylamide gels. However, separation of the rat liver inner
      mitochondrial membrane complexes by blue native gel electrophoresis followed by
      Western blotting, and Western blots of purified Escherichia coli SucDH complex
      revealed that anti-M7 sera contained antibodies directed against the SucDH
      flavoprotein subunit.

PMID- 11982595
TI  - Mechanisms of villous atrophy in autoimmune enteropathy and coeliac disease.
AB  - Since in coeliac disease mucosal flattening has been suggested to result from an
      increased enterocyte apoptosis triggered by Fas/Fas ligand system and perforin
      cytolytic granules, we looked for a similar mechanism in autoimmune enteropathy.
      Moreover, we tried to assess whether enterocyte autoantibodies, which are the
      hallmark of autoimmune enteropathy, may be involved in triggering enterocyte
      apoptosis in this condition. Immunohistochemical staining with anti-Fas, -FasL
      and -perforin MoAb, and TUNEL technique were applied on endoscopic duodenal
      biopsies of two autoimmune enteropathy patients, two untreated coeliac patients
      and two biopsied controls. Cytotoxicity assays were carried out by incubating
      peripheral blood mononuclear cells from a healthy subject (effectors) with
      enterocytes primed with patient or control sera (targets). In autoimmune
      enteropathy a large number of enterocytes were apoptotic, as in coeliac disease,
      whereas neither Fas/Fas ligand or perforin expressions were up-regulated. On the
      other hand, antibody-dependent cellular cytotoxicity assay revealed the ability
      of sera from patients with autoimmune enteropathy to mediate enterocyte death
      through apoptosis. These results point to enterocyte autoantibody-dependent
      cellular cytotoxicity as the prevalent mechanism of increased enterocyte
      apoptosis in autoimmune enteropathy but not in coeliac disease.

PMID- 11982596
TI  - Inflammatory cytokines in small intestinal mucosa of patients with potential
      coeliac disease.
AB  - T helper cell type 1 (Th1) response to gluten has been implicated in the
      pathogenesis of coeliac disease (CD). To characterize immunological activation
      and mild inflammations leading to overt CD in potential coeliac patients, jejunal
      biopsies were obtained from family members of patients with CD or dermatitis
      herpetiformis (DH). Nine family members and one latent CD, eight CD patients and
      eight normal controls furnished jejunal biopsy specimens. Immunohistochemical
      staining of sections for interleukin-1alpha (IL-1alpha), IL-2, IL-4, interferon
      gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), CD3, gammadelta-T
      cell receptor (gammadelta-TCR), and alphabeta-TCR was carried out with monoclonal
      antibodies. Further, expression of IL-4 and IFN-gamma messenger RNA was detected
      by radioactive in situ hybridization in these same samples. In lamina propria, CD
      patients and potential CD patients had higher densities of IL-2 (P = 0.028, P =
      0.043), IL-4 (P = 0.021, P = 0.034) and IFN-gamma positive cells (P = 0.000, P =
      0.009) than did controls. Moreover, CD patients showed a higher density of TNF
      alpha positive cells (P = 0.012, P = 0.001) than the other two groups, and
      expression of IFN-gamma mRNA (P = 0.035) was higher in them than in the other two
      study groups. Additionally, higher densities of TNF-alpha and IFN-gamma positive
      cells occurred in potential CD patients with high gammadelta-TCR+ intraepithelial
      lymphocytes (IELs). Our findings support the hypothesis that lamina propria T
      cells and macrophages, through their secretion of cytokines, play a central role
      in the pathogenesis of coeliac disease. The inflammatory cytokines found in
      potential CD specimens strongly suggest that these inflammatory markers can be
      identified long before visible villous changes have occurred.

PMID- 11982597
TI  - IgA autoreactivity: a feature common to inflammatory bowel and connective tissue
      diseases.
AB  - The immunopathogenic mechanisms in inflammatory bowel disease (IBD) are not yet
      fully established. The aim of this study was to determine the profile and
      magnitude of IgA and IgG autoantibodies in IBD patients. The autoantigen profile
      defined by IgA and IgG antibodies from 24 IBD (14 Crohn's disease CD], 10
      ulcerative colitis UC]), three coeliac, 12 connective tissue disease (CTD)
      patients and 10 healthy individuals was studied in human cellular extracts by
      Western blotting. The magnitude of the IgA and IgG1-4 subclass responses was
      measured by ELISA. IBD patients could not be distinguished from healthy
      individuals on the basis of IgG autoantibodies to Western blotted proteins. IgG
      subclass analysis indicated no clear bias towards Th1 or Th2 immune responses in
      IBD or CTD. In accordance with previous work, we found that IgA autoreactivity
      was strongest in coeliac disease patients. Unexpectedly, IBD as well as CTD
      patients exhibited strong IgA autoantibody reactivities to components of similar
      molecular weights (16-80 kD) in intestinal and non-intestinal epithelial cell
      lines. Our data indicate immunopathogenic similarities between IBD and CTD.

PMID- 11982598
TI  - Age-related differences in cell-specific cytokine production by acutely ill
      Malawian patients.
AB  - Age-related changes in human cell-specific cytokine responses to acute illness
      have not been well examined. We therefore evaluated age-related differences in T,
      B and natural killer (NK) peripheral blood lymphocyte cytokine responses of 309
      acutely ill hospitalized people in Malawi, Africa, < 1 month-61 years of age. We
      used four-colour flow cytometry and performed Wilcoxon rank sum and Kruskal
      Wallis tests, Pearson (rp) and Spearman (rs) correlations, and linear and
      logistic regression analyses to control for human immunodeficiency virus
      infection (HIV) status, the percentages of lymphocytes expressing CD4, and the
      nature of the acute infection. The percentages of CD8- and CD8+ T cells producing
      induced IL-8 decreased with age (rs = -0.44 and -0.53). The percentages of T
      cells producing TNF-alpha were higher, and the percentages producing IL-10 were
      lower, in those > or =13 than those < 13 years old (medians: 17.7 versus 10.5 and
      1.4 versus 3.0, respectively). The percentages of CD8- T cells producing IFN
      gamma were higher and stable in those > or =1 year old compared to infants
      (medians: 23.5 versus 10.4); the percentages of NK producing IFN-gamma were
      higher post-infancy and then declined to relatively low levels with increasing
      age. The percentages of T cells producing IL-2 were highest in those 5- <31 years
      old (median 5.6) and lowest in those > or =31 years old (median 1.9). The ratios
      of the percentages of T cells producing IL-4 to those producing IL-8 and to those
      producing IL-10 both increased with age. These data suggest that innate immunity,
      represented by NK IFN-gamma production, dominates in early life. A number of
      shifts occur after infancy and before adolescence, including a proinflammatory
      shift from IL-8 to TNF-gamma and a type 2 shift from IL-10 to IL-4 dominance.
      These findings suggest distinct age-related differences in the human response to
      acute illness and may be useful in directing future efforts at immunomodulatory
      therapies.

PMID- 11982599
TI  - Neonatal dendritic cells are intrinsically biased against Th-1 immune responses.
AB  - Dendritic cells (DCs) were derived from human peripheral blood monocytes or cord
      blood monocytes cultured in the presence of IL-4 and GM-CSF. Adult and cord DCs
      were observed to have comparable immature phenotypes. However, the increase in
      surface expression of HLA-DR and CD86 after addition of LPS was significantly
      attenuated in cord DCs, with CD25 and CD83 expression also markedly reduced. Cord
      DCs were also unable to produce IL-12p70, failed to down-regulate expression of
      the chemokine receptor CCR5 and induced lower levels of IFN-gamma production from
      allogeneic naive CD4+ T cells than their adult counterparts. In contrast, the
      kinetics of the production of TNF-alpha and IL-10 in response to LPS stimulation
      was comparable to adult DCs. The reduced ability of cord DCs to attain a fully
      mature adult phenotype, and to activate naive CD4+ T cells to produce IFN-gamma,
      suggests that they are intrinsically preprogrammed against the generation of Th-1
      immune responses.

PMID- 11982600
TI  - Immunological characterization of Echinococcus granulosus cyclophilin, an
      allergen reactive with IgE and IgG4 from patients with cystic echinococcosis.
AB  - By immunological screening of a cDNA library derived from protoscoleces of
      Echinococcus granulosus with IgE from patients with cystic echinococcosis (CE)
      and allergic manifestations, we isolated a protein identical to E. granulosus
      cyclophilin. The protein, named EA21, has close homology with Malassezia furfur
      cyclophilin allergen (Mal f 6) and with human cyclophilin. Using immunoblotting
      (IB) with a polyclonal antibody specific to EA21, we identified E. granulosus
      cyclophilin both in protoscoleces and in sheep hydatid fluid. Of the 58 sera from
      patients with CE, 29 (50%) were IgE positive to EA21, whereas, despite the high
      sequence homology, none were IgE positive to Mal f 6 or human cyclophilin. Only
      26 of the 58 patients (45%) had IgG specific to EA21, whereas all patients (100%)
      had IgG specific to Mal f 6 and human cyclophilin. IB analysis showed that serum
      IgE-binding reactivity to EA21 differed significantly in patients with and
      without allergic reactions (20 of 25, 80% versus nine of 33, 27%; P < 10(-4)).
      Conversely, five of the 25 patients who had CE-related allergic manifestations
      (20%) and 21 of the 33 who did not (63%) had specific IgG4 (P = 10(-3)) and total
      IgG to EA21. EA21 induced a proliferative response in 15 of 19 (79%) patients'
      PBMC regardless of the allergic manifestations, but it induced no IL-4
      production. Overall, these findings suggest that E. granulosus cyclophilin is a
      conserved, constitutive, parasite protein that does not cross-react with
      cyclophilins from other organisms and is involved in the allergic symptoms
      related to CE.

PMID- 11982602
TI  - Immunophenotypic characterization of peripheral T lymphocytes in Mycobacterium
      tuberculosis infection and disease.
AB  - The cellular immune response probably plays a pivotal role in determining the
      clinical outcome after exposure to Mycobacterium tuberculosis. We used multi
      parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets
      during infection and disease caused by M. tuberculosis. Samples were obtained
      from 71 volunteers to identify the T CD4+ and CD8+ lymphocyte numbers, and the
      activation plus memory/naive phenotypes, as defined by CD38, HLA-DR, CD45RA and
      CD27 markers. Subjects were divided into 18 healthy volunteers without detectable
      reaction to purified protein derivative (PPD-), 18 health care workers with a
      recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC)
      and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison
      analyses, the T CD4+ lymphocyte number of the TBC group was lower than the PPD-
      group (P < 0.05). This difference was apparently lost after treatment. The higher
      and the lower number of naive T CD4+ cells was observed in the PPD- and TBC
      group, respectively. CD8+ T lymphocytes were also statistically different among
      the four groups (P = 0.0002), lower in the TBC group (P < 0.05). CD8+ T
      lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression.
      The percentage distribution of these markers was statistically different between
      the four groups (P = 0.0055). TBC patients had a higher percentage of CD38+ cells
      and mean fluorescence index, suggesting an overall increase of cell activation.
      These results suggest that peripheral T lymphocytes reflect cellular activation
      during TBC, along with possible redistribution of naive, memory/effector and late
      differentiated memory/effector phenotypes in the peripheral blood after infection
      and disease caused by M. tuberculosis.

PMID- 11982601
TI  - Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich
      antigen.
AB  - In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine
      rich antigen, we analysed responses to overlapping 17-mer peptides encompassing
      the whole antigen in non-exposed UK controls, Pakistani leprosy patients and
      tuberculosis patients in both the United Kingdom and Pakistan. This antigen has
      been described as M. leprae-specific, although it has a hypothetical homologue in
      M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with
      peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides
      were recognized more frequently by T cells from tuberculoid leprosy patients than
      those from UK controls, suggesting that such T cell epitopes might have
      diagnostic potential, while other peptides induced greater responses among UK
      control subjects. Short-term cell lines confirmed that these assays detected
      specific T cell recognition of these peptides. However, many tuberculosis
      patients also recognized these potentially specific peptides suggesting that
      there could be a true homologue present in M. tuberculosis.

PMID- 11982603
TI  - Preservation of clonal heterogeneity of the Pneumocystis carinii-specific CD4 T
      cell repertoire in HIV infected, asymptomatic individuals.
AB  - The loss of CD4 lymphocytes in HIV disease associates with opportunistic
      infections. Since diverse CD4 T cell clones respond to an opportunistic pathogen,
      we asked whether CD4 depletion deletes selected clones in the repertoire
      (vertical depletion) or it affects all clones by reducing the cell number in each
      progeny without affecting the overall number of clones (horizontal depletion).
      Understanding this point may help explain the mode of CD4 depletion and the mode
      of immunoreconstitution after therapy. Therefore we examined the CD4 T cell
      repertoire specific for Pneumocystis carinii, a relevant opportunistic pathogen
      in AIDS, in HIV-infected, asymptomatic individuals. We identified two patients of
      36 asymptomatics for lack of proliferation to P. carinii, suggesting selective
      depletion of specific CD4 cells. To investigate clonal heterogeneity of P.
      carinii-responsive CD4 lymphocytes, specific CD4 T cell lines were generated and
      studied by TCR BV gene family usage and CDR3 length analysis (spectratyping).
      Clonal heterogeneity was similar in antigen-specific CD4 lines generated from P.
      carinii non-responding HIV seropositives and from controls. Thus, despite
      undetectable response to the pathogen, residual specific cells probably prevent
      overt infection and, when expanded in vitro, exhibit a clonal diversity similar
      to normal controls. These findings suggest a horizontal, rather than vertical,
      depletion in these asymptomatic patients.

PMID- 11982604
TI  - Inflammatory responses in Ebola virus-infected patients.
AB  - Ebola virus subtype Zaire (Ebo-Z) induces acute haemorrhagic fever and a 60-80%
      mortality rate in humans. Inflammatory responses were monitored in victims and
      survivors of Ebo-Z haemorrhagic fever during two recent outbreaks in Gabon.
      Survivors were characterized by a transient release in plasma of interleukin
      1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNFalpha), macrophage
      inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta early in the disease,
      followed by circulation of IL-1 receptor antagonist (IL-1RA) and soluble
      receptors for TNFalpha (sTNF-R) and IL-6 (sIL-6R) towards the end of the
      symptomatic phase and after recovery. Fatal infection was associated with
      moderate levels of TNFalpha and IL-6, and high levels of IL-10, IL-1RA and sTNF
      R, in the days before death, while IL-1beta was not detected and MIP-1alpha and
      MIP-1beta concentrations were similar to those of endemic controls. Simultaneous
      massive activation of monocytes/macrophages, the main target of Ebo-Z, was
      suggested in fatal infection by elevated neopterin levels. Thus, presence of IL
      1beta and of elevated concentrations of IL-6 in plasma during the symptomatic
      phase can be used as markers of non-fatal infection, while release of IL-10 and
      of high levels of neopterin and IL-1RA in plasma as soon as a few days after the
      disease onset is indicative of a fatal outcome. In conclusion, recovery from Ebo
      Z infection is associated with early and well-regulated inflammatory responses,
      which may be crucial in controlling viral replication and inducing specific
      immunity. In contrast, defective inflammatory responses and massive
      monocyte/macrophage activation were associated with fatal outcome.

PMID- 11982605
TI  - Detection of antivimentin antibody in sera of patients with idiopathic pulmonary
      fibrosis and non-specific interstitial pneumonia.
AB  - It has been suggested that the humoral immune system plays a role in the
      pathogenesis of non-specific interstitial pneumonia (NSIP). Although some
      circulating autoantibodies to cytoskeletal protein(s) have been suggested, the
      antimyofibroblast antibody has not been investigated in patients with idiopathic
      pulmonary fibrosis (IPF) and NSIP. The purpose of this study is to evaluate the
      existence of antimyofibroblast antibody in the sera of patients with IPF and
      NSIP. The MRC5 cell line was used as a model of myofibroblast. The anti-MRC5 cell
      antibody was characterized in a patient with NSIP using Western blotting. Since
      we found that one of the anti-MRC5 antibodies was an antivimentin antibody, we
      established an enzyme-linked immunosorbent assay (ELISA) to measure the levels of
      antivimentin antibody in the sera of patients with IPF (n = 12) and NSIP (n =
      23). Initially, two anti-MRC5 cell antibodies were detected in the sera of
      patients with NSIP, one of which was characterized as the antivimentin antibody
      by Western blotting. The other was characterized as an antivimentin fragment
      antibody. We established an ELISA to measure the antivimentin antibody and found
      significantly higher levels in patients with IPF and NSIP than in normal
      volunteers. One of the anti-MRC5 cell antibodies in the serum of a patient with
      NSIP was against vimentin. The serum levels of antivimentin antibody were
      increased in patients with IPF and NSIP compared with that of normal volunteers.
      These results suggest that the antivimentin antibody may be involved in the
      process of lung injury in IPF and NSIP.

PMID- 11982606
TI  - Activation-induced T cell death, and aberrant T cell activation via TNFR1 and
      CD95-CD95 ligand pathway in stable cardiac transplant recipients.
AB  - Specific blockade by antibodies (Abs) utilized in induction therapy may cause
      activation-induced cell death (AICD) in lymphocytes of transplant recipients,
      preactivated via CD95 and tumour necrosis factor-alpha receptor type 1 (TNFR1),
      and reduce allograft rejection frequency. Amongst 618 heart transplant (HTX)
      patients receiving antithymocytes globulin (ATG) therapy, 14 recipients with IVUS
      verified freedom of transplant vasculopathy were studied. The control group
      contained 14 patients awaiting transplantation, classified by the New York Hearth
      Association heart failure as class IV. From 618 HTX patients 89% were free of
      rejection grade ISHLT > or =2-3 within 3-month post transplantation and 86% after
      one year. The death inducing receptors (DIR) such as CD95, CD95L and soluble
      TNFR1 were significantly increased in HTX recipients versus controls, as
      demonstrated by FACS, immunoblotting or ELISA (P < 0.001). The presence of
      increased DIR and in vivo apoptosis in HTX recipients, indicated by annexin-V
      binding, was further confirmed by the presence of high concentration of histones
      in the sera of patients. ATG, anti-IL-2R and OKT-3 Abs inhibited cell
      proliferation in a dose-dependent manner. The induction of apoptosis and/or
      necrosis was demonstrated in cells cultured with these Abs by annexin-V and 7
      aminoactinomycin staining, respectively. Our findings demonstrate that T cells
      from HTX recipients express high level of CD95, CD95L and soluble TNFR1, and
      undergo apoptosis and AICD. These cells recognizing donor alloantigens may be
      selectively eliminated in vivo, and should be responsible for the observed
      immunological unresponsiveness, indicated by low rejection rates in our patient
      cohort treated by conventional triple therapy.

PMID- 11982608
TI  - Infectious disease prophylaxis in renal transplant patients: a survey of US
      transplant centers.
AB  - Definitive approaches to most infectious diseases following renal transplantation
      have not been established, leading to different approaches at different
      transplant centers. To study the extent of these differences, we conducted a
      survey of the practices surrounding specific infectious diseases at US renal
      transplant centers. A survey containing 103 questions covering viral, bacterial,
      mycobacterial and protozoal infections was developed. Surveys were sent to
      program directors at all U.S. renal transplant centers. Responses were received
      from 147 of 245 (60%) transplant centers and were proportionately represented all
      centers with respect to program size and geographical location. Pre-transplant
      donor and recipient screening for hepatitis B virus (HBV), hepatitis C virus
      (HCV), human immunodeficiency virus (HIV) and cytomegalovirus (CMV) is uniform,
      but great discrepancy exists in the testing for other agents. HCV seropositive
      donors are used in 49% of centers. HIV seropositivity remains a contraindication
      to transplantation, although 13% of centers indicated they have experience with
      such patients. Post-transplant, there is wide variety in approach to CMV and
      Pneumocystis carinii (PCP) prophylaxis. Similarly divergent practices affect post
      transplant vaccinations, with 54% of centers routinely vaccinating all patients
      according to customary guidelines in non-transplant populations. In contrast, 22%
      of centers indicated they do not recommend vaccination in any patients. We
      believe an appreciation of the differences in approaches to post-transplant
      infectious complications may encourage individual centers to analyse the results
      of their own practices. Such analysis may assist in the design of studies to
      answer widespread and important questions regarding the care of patients
      following renal transplantation.

PMID- 11982607
TI  - Elevated monocytic IL-12 and TNF-alpha production in Wegener's granulomatosis is
      normalized by cyclophosphamide and corticosteroid therapy.
AB  - Wegener's granulomatosis (WG) is characterized by a predominance of the type 1 T
      helper cell (Th1) response. We have studied monocytic cytokine expression in
      untreated patients and in patients who did not respond to prior methotrexate or
      trimethoprim-sulphamethoxazole therapy, i.e. patients with active disease.
      Intracytoplasmic IL-12 and TNF-alpha expression was significantly increased in WG
      compared with healthy controls. IL-8 expression was not increased. Two and 12
      weeks of daily standard oral cyclophosphamide and corticosteroid (CYC + GC)
      treatment induced a stable remission of the disease. Elevated IL-12 and TNF-alpha
      expression of monocytes was normalized. The active metabolite of CYC was shown to
      down-regulate IL-12 mRNA in vitro. Monocytic cytokines, especially IL-12, may
      have a role in the early determination and skewing of the immunoregulatory
      response towards a Th1 profile. It appears that CYC + GC exerts its effect by
      normalizing the Th1-driving cytokine pattern, and CYC may maintain this mode of
      action. Normalization of the skewed cytokine pattern may be a prerequisite and an
      indicator of inducing a remission in WG.

PMID- 11982609
TI  - Plasma amino acids in cirrhosis and after liver transplantation: influence of
      liver function, hepatic hemodynamics and circulating hormones.
AB  - Liver cirrhosis is characterized by substantial changes in amino acid (AA)
      metabolism, resulting in a deranged plasma AA profile. To investigate the effect
      of liver transplantation (OLT), we studied arterial AA profiles in 52 patients
      with advanced cirrhosis, 16 stable patients over 6 months after OLT and 48
      controls. Changes in AA levels were correlated with portal pressure (hepatic
      venous pressure gradient), functional hepatic blood flow (indocyanine green
      extraction) and circulating hormone levels (catecholamines, insulin, C-peptide).
      Fourteen of 18 measured AA were significantly altered in cirrhosis and 11 of 18
      remained abnormal after OLT compared with controls. Aromatic AA (AAA) and
      methionine were elevated in cirrhosis (p < 0.001 each), increasing with disease
      stage, and normalized after OLT. Branched chain AA (BCAA) levels were decreased
      in cirrhosis (p < 0.001) and were unrelated to disease stage. After OLT, BCAA
      levels remained subnormal (p < 0.01), although higher than in cirrhosis (p <
      0.001). AAA levels increased with decreasing functional hepatic blood flow (r = 
      0.67; p < 0.001) and increasing portal pressure (r = 0.59; p < 0.001). BCAA
      levels decreased with increasing catecholamine (r = - 0.54, p < 0.001) and
      insulin levels (r = - 0.40, p = 0.001). We conclude that despite normal liver
      function, AA metabolism is only partially normalized after OLT. AAA levels mainly
      determined by hepatic metabolic function and functional liver blood flow return
      to normal, while BCAA levels remain subnormal, indicating persistent changes in
      muscular AA metabolism after OLT.

PMID- 11982610
TI  - Influence of dialysis on post-transplant events.
AB  - INTRODUCTION: We examined the effect of haemodialysis (HD) or peritoneal dialysis
      (PD) on acute rejection, delayed graft function (DGF), graft and patient survival
      after cadaveric renal transplantation. MATERIALS AND METHODS: We carried out a
      retrospective analysis of 325 patients (cyclosporin [CyA]-based therapy) who had
      their first cadaver renal transplant between January 1991 and December 1996 and
      followed up for a mean of 61 +/- 26 months. They were divided into three groups:
      HD, PD and CD (where both PD and HD was used for at least 3 months). Delayed
      graft function was diagnosed if the patient needed dialysis in the first week
      post-transplant while primary non-function (PNF) was diagnosed if the kidney
      never achieved function. Graft rejection was confirmed by biopsy; early acute
      rejection (EAR) was defined as acute rejection occurring before 90 days and late
      acute rejection (LAR) as one after 90 d. RESULTS: A total of 183 patients had PD,
      117 HD and 25 CD. The mean time period in which the patients were on dialysis for
      PD was 24 months, HD 34.5 months and CD 50.6 months (p < 0.01). The recipients
      were matched for age and gender. The donor variables (age, gender and cold
      ischaemia time) did not differ between the groups. The mean time for the
      development of first acute rejection following renal transplant in each group was
      as follows: PD group: 68.8 d, HD group: 81.3 d and CD group: 105 d (p = 0.08).
      The number of patients who developed EAR was 90 (49.2%) in PD group, 51 (43.6%)
      in HD group and 11 (56%) in CD group (p = 0.6); the number who developed LAR was
      nine in PD group (4.9%), six in HD group (5.1%) and one in CD group (4%) (p =
      0.9). Fifty-six patients with PD had DGF compared with 58 with HD (p = 0.01).
      There was no difference in the number and severity of rejection episodes or DGF
      based on the duration of dialysis. The 5-yr survival of patients was 79% for PD,
      81% HD and 78% CD groups (p = n.s), while the graft survival for PD group was
      61%, HD group 63% and CD group 74% (p = n.s). SUMMARY: We could find no
      difference in the patient or graft survival between patients who had pre
      transplant HD, PD or CD. There was no difference in the incidence of acute
      rejection episodes between the three groups of patients as well. However, we
      found a significantly higher rate of DGF in the HD versus PD patients.

PMID- 11982611
TI  - Live donor renal transplants using kidneys with arteriographic evidence of mild
      renovascular disease.
AB  - The objective of the study was to determine whether using a living donor kidney
      with arteriographic evidence of renovascular disease affects the outcome of the
      recipient's transplanted graft. Twenty-eight patients who had unilateral
      renovascular abnormalities on conventional angiography underwent donor
      nephrectomy of the ipsilateral kidney. Results in the recipients who received
      these kidneys were reviewed. Comparison was made to a control group of living
      donor renal transplant recipients who were matched for donor, recipient age.
      Graft survival, patient survival, serum creatinine for all 28 recipients were
      evaluated. All 28 donors underwent a successful donor nephrectomy. Recipient
      graft survival was 96% at 1 yr, 92% at 3 yr, 71% at 5 yr, 62% at 10 yr. Mean
      serum creatinine values at 1 month, 1 yr, 3 yr were 1.5, 1.5, 1.6, respectively.
      Similar results were observed in the control group. We conclude that renal
      transplantation utilizing kidneys with arteriographic evidence of renovascular
      disease results in excellent short, long-term renal allograft survival.

PMID- 11982612
TI  - Enhancing transplant patients' adherence to medication therapy.
AB  - Despite the importance of proper medication use, many transplant patients do not
      take their medications correctly. Non-adherence to medication therapy leads to
      adverse consequences, and practitioners should encourage adherence by transplant
      patients. This manuscript discusses several aspects of medication taking behavior
      including: (1) methods of identifying medication non-adherence; (2) models used
      to identify possible determinants of medication taking behavior; (3) strategies
      to educate patients concerning their therapy; (4) factors promoting adherence and
      non-adherence; and (5) practical interventions that we, as practitioners, can
      employ to enhance adult and pediatric transplant patients' adherence to therapy.
      By using the strategies suggested, transplant patients' adherence to medication
      therapy may be enhanced and patients' quality of life improved.

PMID- 11982613
TI  - Good metabolic control using tacrolimus-based immunosuppressants in primary
      cadaveric renal transplantation in Chinese--a preliminary report.
AB  - Metabolic complications are common with tacrolimus therapy. Recent evidence
      suggests that there is ethnical variability in the side-effect profile of
      tacrolimus. We performed an open-label study to examine the metabolic profile of
      tacrolimus-based immunosuppressive therapy in 10 consecutive adult Chinese
      patients after cadaveric renal transplantation. One case withdrew because of
      parvovirus infection. The mean age of the remaining nine cases was 33 +/- 2.9 yr.
      Mean tacrolimus whole blood trough level at 0 and 12 months were 11.4 +/- 1.8 and
      7.0 +/- 0.7 ng/mL, respectively. The dosage at corresponding time points were
      0.31 +/- 0.001 and 0.10 +/- 0.003 mg/kg, respectively. We found no difference in
      lipid profile, blood pressure control, and most importantly, fasting glucose
      level, before and I yr after tacrolimus therapy. Standard 75-g oral glucose
      tolerance test and whole blood HbAlc level were normal in all patients. Our
      preliminary data suggest good short-term safety among Chinese renal
      transplantation recipients after tacrolimus-based immunosuppressants, with a very
      low incidence of hyperglycemia, hypertension and dyslipidemia. The long-term
      implications and the underlying explanation for this ethnical difference require
      further investigations.

PMID- 11982614
TI  - Rapid kidney allograft failure in patients with polyoma virus nephritis with
      prior treatment with antilymphocyte agents.
AB  - Interstitial nephritis owing to polyoma virus infection (PVi) mimics acute
      allograft rejection. The risk factors for graft failure associated with PVi are
      unknown. This prompted us to analyse the relationship between the use of
      antilymphocyte agents (ALA) and graft dysfunction in renal transplant recipients
      with PVi. Renal transplant recipients who were diagnosed to have PVi nephritis at
      the Medical College of Wisconsin were included in this study. PVi nephritis was
      confirmed by urine cytology and characteristic renal histological findings in a
      total of 14 cases. Other viruses were excluded by immunohistochemistry studies.
      Patients were divided into two groups: Group A (n = 7) received ALA (OKT3/ATGAM)
      as treatment for presumptive acute rejection and Group B (n = 7) did not receive
      ALA therapy. The progression of renal function (GFR) was estimated by a 100/
      plasma creatinine and an actuarial kidney survival was estimated by the Kaplan
      Meier method. The demographics (age, gender, race, retransplant and kidney
      versus. kidney/pancreas), prior treatment with steroids for presumptive acute
      rejection, and renal function at the time of PVi diagnosis were similar betwoen
      groups. The fall in GFR/month was 6 mL/min/month with prior ALA therapy compared
      with 1 mL/min/month in those who did not receive ALA, p = 0.002. All seven grafts
      were lost in the ALA group compared with only two of seven grafts in the other
      group, p = 0.005. The use of ALA was associated with a rapid fall in GFR and
      graft failure in patients with PVi nephritis. Careful diagnosis of PVi is
      warranted in renal allograft recipients prior to initiating ALA therapy.

PMID- 11982615
TI  - Quality of life in kidney recipients: comparison of tacrolimus and cyclosporine
      microemulsion.
AB  - Treatment of end-stage renal disease (ESRD) is evaluated by survival, quality of
      life (QOL) and cost-effectiveness. Little is known about the influence of
      immunosuppressive agents on global and disease-specific QOL in kidney recipients.
      In winter 1997/98 (t0) as well as in winter 1998/99 (t1), all kidney recipients
      of our University were asked to participate in a QOL study. The psychodiagnostic
      approach combined a global QOL-measure (SF-36 Health Survey) and a disease
      specific questionnaire (ESRD-SCL, Nephron 1999). Inclusion criteria for the final
      analysis were (a) participation in both surveys and (b) eligibility after the
      matching procedure: patients with tacrolimus-based immunosuppressive regimen were
      matched to patients with cyclosporin-microemulsion (CsA-ME)-based
      immunosuppressive-regimen as to age, gender and duration of graft function. Group
      data were compared by performing a two-variate ('immunosuppression', 'time')
      analysis of variance. Both groups consisted of 63 patients. Analysis of QOL
      revealed statistically significant advantages for the tacrolimus treated patients
      concerning global (SF-36 'Physical Component Summary') as well as disease
      specific QOL (ESRD-SCLTM 'Global Severity Index'; both p < 0.05). In detail,
      these results were due to statistically significant better QOL in tacrolimus
      treated patients as to the SF-36 subscales 'Physical Functioning' and 'General
      Health' (p < 0.05) and the ESRD-SCL subscales 'Limited Physical Capacity' (p <
      0.05), 'Cardial and Renal Dysfunction' (p < 0.01) and 'Increased Growth of Gum
      and Hair' (p < 0.001). The factor 'time' did not contribute statistically
      significant to explanation of variance. In terms of QOL in kidney recipients,
      tacrolimus is superior to CsA-ME. Tacrolimus improves disease-specific QOL and
      also shows slight advantages concerning global QOL compared with CsA-ME. To
      record differentiated aspects of QOL in kidney recipients, the diagnostic
      approach should include a global QOL measure completed by a sensitive disease
      specific instrument.

PMID- 11982616
TI  - Psychosocial data of potential living donors before living donor liver
      transplantation.
AB  - In view of the scarcity of organ resources for transplantation, donation by
      living donors is assuming greater significance now that the technical-surgical
      problems involved have been solved. In the period between December 1999 and
      December 2000, 47 potential living liver donors were evaluated and a total of 27
      hepatic lobes were transplanted at the Virchow-Klinikum of the Charite Hospital
      in Berlin. The close personal relationships between recipients and donors gives
      reason to anticipate high levels of psychosocial pressure during the pre
      operative evaluation process; this process consists in part in looking into donor
      motivation, ambivalence and anxiety. The pre-operative psychometric evaluation of
      40 potential living donors indicated that most of the potential donors see
      themselves as 'super-healthy' and tend to adapt to social expectations, while on
      the other hand those seven potential living donors not accepted for psychosocial
      reasons were marked by heightened values for anxious depression and pessimism.
      The results indicate in most cases a great willingness to donate and on the other
      hand a high level of obvious psychological pressure for a low number of potential
      donors. For the latter, both the clinical evaluation interview and the
      psychometric diagnostics used revealed clear-cut feelings of anxiety and
      ambivalence towards transplantation.

PMID- 11982617
TI  - A multicenter, open-label, comparative trial of two daclizumab dosing strategies
      vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil,
      and steroids for the prevention of acute rejection in simultaneous kidney
      pancreas transplant recipients: interim analysis.
AB  - INTRODUCTION: The safety and efficacy of daclizumab (1 mg/kg/dose every 14 d for
      five doses) has been established in kidney and heart transplant recipients.
      Alternative dosing regimens based on pharmacokinetic simulation and limited
      clinical trials are being investigated. The purpose of this ongoing multicenter
      study is to determine the safety and efficacy of two dosing regimens of
      daclizumab as an adjunctive immunosuppressive agent compared with no antibody
      induction in simultaneous kidney-pancreas transplant (SKPT) recipients receiving
      tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids as primary
      immunosuppression. METHODS: This is an interim report of a multicenter,
      prospective, open-label, randomized study with a target enrolment of 290
      patients. Eligible SKPT patients were randomized to one of three groups:
      daclizumab 1 mg/kg/dose every 14 d for five doses (Group I), daclizumab 2
      mg/kg/dose every 14 d for two doses (Group II), and no antibody induction (Group
      III). The primary endpoint of the study is a composite of the incidence of
      presumed or biopsy-proven kidney or pancreas rejection, graft loss, or death
      within the first 6 months post-transplantation. RESULTS: A total of 166 patients
      were randomized into the three groups [Group I (n = 70), Group II (n = 74), Group
      III (n = 22)]. Demographic and transplant characteristics were similar among the
      groups. At a minimum follow-up of 3 months, patient, kidney and pancreas graft
      survival rates were similar among the three groups. However, the rates of acute
      renal allograft rejection were 18% (Group I), 8% (Group II), and 36% (Group III),
      p < 0.05. The probabilities of either kidney or pancreas allograft rejection were
      22% (Group I), 8% (Group II), and 38% (Group III). At 3 months, the actuarial
      event-free survival (no acute rejection, allograft loss, or death) rates were 67,
      81 and 50% in Groups I, II, and III, respectively. There were no differences in
      the incidence of infectious complications among the groups and no serious adverse
      events associated with daclizumab were observed. CONCLUSIONS: The two-dose
      regimen (Group II) appears to be as effective as the five-dose regimen (Group I)
      in preventing acute rejection after SKPT and is associated with the lowest acute
      rejection rates and the highest rate of event-free survival (no rejection or
      graft loss). However, the benefits of daclizumab compared with no antibody
      induction await larger sample size accrual.

PMID- 11982618
TI  - Compliance and late acute rejection after kidney transplantation: a psycho
      medical perspective.
AB  - INTRODUCTION: We examined the relationship between late acute rejection (LAR)
      after cadaveric kidney transplantation and medical compliance utilizing a
      modified version of the Long-term Medication Behaviour Self-efficacy Scale (LTMBS
      scale), a validated patient self-report questionnaire. The original LTMBS-scale
      uses a five-point scale, however, our pilot study showed that patients found it
      difficult to discriminate between the five options. We therefore modified this to
      a three-point scale. PATIENTS AND METHODS: We carried out a retrospective
      analysis of all patients who received a kidney transplant in our unit in the
      cyclosporin (CyA) era. We divided rejections into early and late rejection based
      on the time interval after transplantation. Graft rejection was confirmed by
      biopsy; LAR was defined as acute rejection occurring after 90 d. We
      retrospectively administered the modified LTMBS-scale to determine individual
      patient confidence and self-efficacy in taking their medications in a variety of
      situations (home, work, leisure, psychological and physical). Individual patient
      confidence and self-efficacy was analysed in relationship to compliance
      behaviour. RESULTS: Twenty-four questionnaires were distributed, 22 (92%) were
      returned fully completed. The overall results suggested that our patients
      surveyed were not particularly confident (mean score 2.17 out of maximum possible
      3) in taking their medications in a variety of contexts. They demonstrated
      significantly less confidence (mean score 1.0) when experiencing physical
      (brittle bones, feeling 'ill') and psychological ('sadness') side-effects of
      medication and emotional reactions to the experience of chronic illness.
      CONCLUSION: Negative physical and psychological states were related to low self
      efficacy with the taking of immunosuppressive medication, non-compliance and
      subsequent LAR in our cohort of patients.

PMID- 11982619
TI  - Effective treatment of autoimmune hemolytic anemia and hairy cell leukemia with
      interferon-alpha.

PMID- 11982620
TI  - Long lasting myelodysplastic syndrome complicated by autoimmune hemolytic anemia
      and non-Hodgkin's lymphoma.

PMID- 11982621
TI  - Glycinergic and GABAergic calcium responses in the developing lateral superior
      olive.
AB  - The lateral superior olive (LSO), a binaural nucleus involved in sound
      localization, receives tonotopically organized inhibitory inputs from the medial
      nucleus of the trapezoid body (MNTB). During development, the tonotopic
      organization of this glycinergic/GABAergic MNTB-LSO pathway is established by
      activity-dependent axonal reorganization. However, the underlying mechanisms by
      which this reorganization takes place have remained largely unknown. As cytosolic
      calcium is one of the most important second messengers responsible for inducing
      synaptic plasticity and reorganization, we examined whether and how activity in
      the MNTB-LSO pathway changes the intracellular calcium concentration ([Ca2+]i) in
      developing LSO neurons. By applying calcium imaging techniques to Fura-2-labelled
      slices from neonatal rats and mice, we found that glycine and GABA (gamma
      aminobutyric acid) affect [Ca2+]i in LSO neurons in an age-dependent manner;
      during the first postnatal week, the period at which glycine and GABA are
      depolarizing in the LSO, glycine and GABA always increased [Ca2+]i. However, in 2
      week-old animals, the time around hearing onset when glycine and GABA are
      hyperpolarizing, glycine and GABA slightly decreased [Ca2+]i. Calcium responses
      could also be elicited by stimulation of afferent fibres from the MNTB, and these
      synaptic responses were mediated by glycine and GABA(A) receptors. Furthermore,
      GABA, which is a neurotransmitter only in the immature MNTB-LSO pathway, played a
      major role in generating MNTB-elicited Ca2+ responses. The direct link of
      glycinergic/GABAergic synaptic activity to intracellular calcium signalling
      during the period of inhibitory synaptic plasticity could be one of the
      mechanisms by which tonotopic MNTB-LSO connections become established.

PMID- 11982622
TI  - Seizure-dependent modulation of mitochondrial oxidative phosphorylation in rat
      hippocampus.
AB  - Mitochondrial function is a key determinant of both excitability and viability of
      neurons. Here, we demonstrate seizure-dependent changes in mitochondrial
      oxidative phosphorylation in the epileptic rat hippocampus. The intense
      pathological neuronal activity in pilocarpine-treated rats exhibiting spontaneous
      seizures resulted in a selective decline of the activities of NADH-CoQ
      oxidoreductase (complex I of the respiratory chain) and cytochrome c oxidase
      (complex IV of respiratory chain) in the CA3 and CA1 hippocampal pyramidal
      subfields. In line with these findings, high-resolution respirometry revealed an
      increased flux control of complex I on respiration in the CA1 and CA3 subfields
      and decreased maximal respiration rates in the more severely affected CA3
      subfield. Imaging of mitochondrial membrane potential using rhodamine 123 showed
      a lowered mitochondrial membrane potential in both pyramidal subfields. In
      contrast to the CA1 and CA3 subfields, mitochondrial oxidative phosphorylation
      was unaltered in the dentate gyrus and the parahippocampal gyrus. The changes of
      oxidative phosphorylation in the epileptic rat hippocampus cannot be attributed
      to oxidative enzyme modifications but are very likely related to a decrease in
      mitochondrial DNA copy number as shown in the more severely affected CA3 subfield
      and in cultured PC12 cells partially depleted of mitochondrial DNA. Thus, our
      results demonstrate that seizure activity downregulates the expression of
      mitochondrial-encoded enzymes of oxidative phosphorylation. This mechanism could
      be invoked during diverse forms of pathological neuronal activity and could
      severely affect both excitability and viability of hippocampal pyramidal neurons.

PMID- 11982623
TI  - Intrinsic GABA neurons inhibit proenkephalin gene expression in slice cultures of
      rat neostriatum.
AB  - In the neostriatum, the proenkephalin gene is expressed in medium spiny GABA
      neurons, which project to the globus pallidus. The expression is activated by
      glutamatergic projections from the neocortex via NMDA receptors. In these
      experiments we have used slice cultures of rat neostriatum to study the role of
      GABA in proenkephalin gene expression. Our results show that GABA is released
      from neostriatal neurons and negatively regulates the proenkephalin gene
      expression induced by NMDA receptor stimulation. The GABAA receptors involved
      seem to be colocalized with NMDA receptors on the projection neurons, which
      express the proenkephalin gene. In further experiments, we have found that the
      proenkephalin gene expression is not only activated by neocortical projection
      neurons but also by intrinsic striatal neurons as well as by projections from the
      thalamus. All these glutamatergic afferents enhance the proenkephalin gene
      expression via NMDA receptors. Their efficacy is regulated by endogenous GABA.

PMID- 11982624
TI  - The histaminergic system in human thalamus: correlation of innervation to
      receptor expression.
AB  - The mRNA expression of three histamine receptors (H1, H2 and H3) and H1 and H3
      receptor binding were mapped and quantified in normal human thalamus by in situ
      hybridization and receptor binding autoradiography, respectively.
      Immunohistochemistry was applied to study the distribution of histaminergic
      fibres and terminals in the normal human thalamus. mRNAs for all three histamine
      receptors were detected mainly in the dorsal thalamus, but the expression
      intensities were different. Briefly, H1 and H3 receptor mRNAs were relatively
      enriched in the anterior, medial, and part of the lateral nuclei regions; whereas
      the expression level was much lower in the ventral and posterior parts of the
      thalamus, and the reticular nucleus. H2 receptor mRNA displayed in general very
      low expression intensity with slightly higher expression level in the anterior
      and lateropolar regions. H1 receptor binding was mainly detected in the
      mediodorsal, ventroposterolateral nuclei, and the pulvinar. H3 receptor binding
      was detected mainly in the dorsal thalamus, predominantly the periventricular,
      mediodorsal, and posterior regions. Very high or high histaminergic fibre
      densities were observed in the midline nuclear region and other nuclei next to
      the third ventricle, ventroposterior lateral nucleus and medial geniculate
      nucleus. In most of the core structures of the thalamus, the fibre density was
      very low or absent. The results suggest that histamine in human brain regulates
      tactile and proprioceptory thalamocortical functions through multiple receptors.
      Also, other, e.g. visual areas and those not making cortical connections
      expressed histamine receptors and contained histaminergic nerve fibres.

PMID- 11982625
TI  - Whole-cell recording from honeybee olfactory receptor neurons: ionic currents,
      membrane excitability and odourant response in developing workerbee and drone.
AB  - Whole-cell recording techniques were used to characterize ionic membrane currents
      and odourant responses in honeybee olfactory receptor neurons (ORNs) in primary
      cell culture. ORNs of workerbee (female) and drone (male) were isolated at an
      early stage of development before sensory axons connect to their target in the
      antennal lobe. The results collectively indicate that honeybee ORNs have
      electrical properties similar, but not necessarily identical to, those currently
      envisaged for ORNs of other species. Under voltage clamp at least four ionic
      currents could be distinguished. Inward currents were made of a fast transient,
      tetrodotoxin-sensitive sodium current. In some ORNs a cadmium-sensitive calcium
      current was detected. ORNs showed heterogeneity in their outward currents: either
      outward currents were made of a delayed rectifier type potassium current, which
      was partially blocked by tetraethyl ammonium or quinidine, or were composed of a
      delayed rectifier type and a transient calcium-dependent potassium current, which
      was cadmium-sensitive and abolished by removal of external calcium. The
      proportion of each of the two outward currents, however, was different within the
      ORNs of the two sexes suggesting a gender-specific functional heterogeneity. ORNs
      showed heterogeneity in action potential firing properties: depolarizing current
      steps elicited either one action potential or, as in most of the cells, it led to
      repetitive spiking. Action potentials were tetrodotoxin-sensitive suggesting they
      are carried by sodium. Odourant stimulation with different mixtures and pure
      substances evoked depolarizing receptor potentials with superimposed action
      potentials when spike threshold was reached. In summary, honeybee ORNs are
      remarkably mature at early stages in their development.

PMID- 11982626
TI  - Gradients in the circadian expression of Per1 and Per2 genes in the rat
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) is the mammalian circadian pacemaker, which
      consists of thousands of oscillator cells. It is believed that the circadian
      oscillation in each cell is generated by the transcription/(post)-translation
      feedback loop of a set of clock genes. However, little is known about how these
      oscillator cells are organized to produce the robust circadian rhythms in the
      SCN. In the present study, we examined the expression of the clock genes Per1 and
      Per2 paying particular attention to the topographic compartmentalization of the
      SCN. In the rat SCN, the dorsomedial (SCNDM) and ventrolateral (SCNVL)
      compartments are clearly delineated by chemical characteristics of neurons and
      neuronal afferents. In the SCNDM, Per1 mRNA was initially expressed at the most
      dorsomedial region along the third ventricle (SCNDMPV, periventricular part of
      the dorsomedial compartment of the SCN) at CT0, and then spread laterally to the
      central dorsomedial region (SCNDMCe, central part of the dorsomedial compartment
      of the SCN), reaching peaks at subjective day and troughs at subjective night. In
      contrast, in the SCNVL, Per1 expression showed a weak, two-peak pattern in one
      circadian cycle. Per2 expression was also robust in the SCN, showing very similar
      circadian profiles among these three subdivisions with a slightly earlier phase
      in SCNDMPV than that in SCNDMCe. We also investigated the Per1 and Per2
      expression in response to a light exposure at early subjective night. The light
      pulse induced both Per1 and Per2 expression, which was restricted in the SCNVL
      neurons. The present findings suggest that the phase and amplitude of the
      circadian expression of clock genes are not uniform, and there are topographic
      neuron groups that have different properties in the SCN.

PMID- 11982627
TI  - Developmental expression of the cellular prion protein in elongating axons.
AB  - PrPc, a sialoglycoprotein present in the normal adult hamster brain, is
      particularly abundant in plastic brain regions but little is known about the
      level of expression and the localization of the protein during development.
      Western blot analysis of whole brain homogenates with mab3F4 show very low levels
      of the three main molecular weight forms of the protein at birth, in contrast to
      the strong and wide expression of mRNA transcripts. The PrPc levels increase
      sharply through P14 and are diminished somewhat in the adult. Regional analysis
      showed that in structures with ongoing growth or plasticity such as the olfactory
      bulb and hippocampus, PrPc remains high in the adult, while in areas where
      structural and functional relationships stabilize during development, such as the
      cortex and the thalamus, PrPc levels decline after the third postnatal week. In
      the neonate brain PrPc was prominent along fiber tracts similar to markers of
      axon elongation and in vitro experiments showed that the protein was present on
      the surface of elongating axons. PrPc is then localized to the synaptic neuropil
      in close spatio-temporal association with synapse formation. The localization of
      PrPc on elongating axons suggests a role for the protein in axon growth. In
      addition, the relative abundance of the protein in developing axon pathways and
      during synaptogenesis may provide a basis for the age-dependent susceptibility to
      transmissible spongiform encephalopathies.

PMID- 11982628
TI  - Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout
      mice: correlation with behaviour.
AB  - Anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG)
      are the most active endocannabinoids at brain (CB1) cannabinoid receptors. CD1
      mice lacking the CB1 receptors ("knockout" [KO] mutants) were compared with
      wildtype (WT) littermates for their ability to degrade AEA through an AEA
      membrane transporter (AMT) and an AEA hydrolase (fatty acid amide hydrolase,
      FAAH). The age dependence of AMT and FAAH activity were investigated in 1- or 4
      month-old WT and KO animals, and found to increase with age in KO, but not WT,
      mice and to be higher in the hippocampus than in the cortex of all animals. AEA
      and 2-AG were detected in nmol/mg protein (microm) concentrations in both
      regions, though the hippocampus showed approximately twice the amount found in
      the cortex. In the same regions, 2-AG failed to change across groups, while AEA
      was significantly decreased (approximately 30%) in hippocampus, but not in
      cortex, of old KO mice, when compared with young KO or age-matched WT animals. In
      the open-field test under bright light and in the lit-dark exploration model of
      anxiety, young KO mice, compared with old KO, exhibited a mild anxiety-related
      behaviour. In contrast, neither the increase in memory performance assessed by
      the object recognition test, nor the reduction of morphine withdrawal symptoms,
      showed age dependence in CB1 KO mice. These results suggest that invalidation of
      the CB1 receptor gene is associated with age-dependent adaptive changes of
      endocannabinoid metabolism which appear to correlate with the waning of the
      anxiety-like behaviour exhibited by young CB1 KO mice.

PMID- 11982629
TI  - Sub-chronic treatment with classical but not atypical antipsychotics produces
      morphological changes in rat nigro-striatal dopaminergic neurons directly related
      to "early onset" vacuous chewing.
AB  - In the present work, we investigated if an impairment of dopaminergic neurons
      after subchronic haloperidol treatment might be a possible physiopathologic
      substrate of the "early onset" vacuous chewing movements (VCMs) in rats. For this
      purpose, different antipsychotics were used to analyse a possible relationship
      between VCMs development and morphological alterations of tyrosine-hydroxylase
      immunostained (TH-IM) neurons. Rats treated twice a day with haloperidol
      displayed a significant increase of VCMs that was both time- (2-4 weeks) and dose
      (0.1-1 mg/kg) dependent. Immunocytochemical analysis showed a shrinkage of TH-IM
      cell bodies in substantia nigra pars compacta and reticulata and a reduction of
      TH-immunostaining in the striatum of haloperidol treated rats with the arising of
      VCMs. No differences were observed in TH-IM neurons of ventral tegmental area and
      nucleus accumbens vs. control rats. The atypical antipsychotics risperidone (2
      mg/kg, twice a day), amisulpride (20 mg/kg, twice a day) and clozapine (10 mg/kg,
      twice a day) did not produce any nigro-striatal morphological changes or VCMs. TH
      IM nigro-striatal neuron morphological alterations and VCMs were still present
      after three days of withdrawal in rats treated for four weeks with haloperidol (1
      mg/kg). Both the main morphological changes and the behavioural correlate
      disappeared after three weeks of withdrawal. These results suggest that
      haloperidol induces a morphological impairment of the dopaminergic nigro-striatal
      neurons which is directly associated with the arising, permanency and
      disappearance of VCMs in rats.

PMID- 11982630
TI  - Preferential alterations in the mesolimbic dopamine pathway of heterozygous
      reeler mice: an emerging animal-based model of schizophrenia.
AB  - Based on a number of neuroanatomical and behavioural similarities, recent
      evidence suggests that heterozygous reeler mice, haploinsufficient for reelin
      expression, represent a useful model of psychosis vulnerability. As brain
      mesolimbic dopamine pathways have been proposed to be associated with the
      pathophysiology of psychotic disorders, we thought it would be of interest to
      examine whether these animals present disturbances in the mesolimbic dopamine
      system. To this end we studied by immunocytochemical, in situ hybridization
      procedures and receptor autoradiography, several markers of the mesotelencephalic
      dopamine pathway in heterozygous reeler mice and controls. We report that
      heterozygous reeler mice exhibit a reduction in the number of tyrosine
      hydroxylase-immunoreactive cell bodies and tyrosine hydroxylase mRNA levels in
      the ventral tegmental area, as well as a reduction of tyrosine hydroxylase and
      dopamine transporter immunoreactivity in the dopamine terminal fields of the
      limbic striatum. In these areas we also observed a reduction of dopamine D2
      receptor mRNA. Finally, a marked increase in D3 receptor mRNA levels was observed
      concomitant with a significant increase in D3 binding sites. On the contrary, the
      nigrostriatal pathway did not show any significant alteration in heterozygous
      reeler mice with regards to the dopaminergic markers examined in substantia nigra
      cell bodies and dorsal striatum dopamine terminal fields. These results suggest a
      specific link between reelin-related neuronal pathology and dopamine involvement
      in the pathophysiology of psychotic disorders.

PMID- 11982631
TI  - Contribution of amygdala neurons containing peptides and calcium-binding proteins
      to fear-potentiated startle and exploration-related anxiety in inbred Roman high-
      and low-avoidance rats.
AB  - The purpose of this study was to investigate amygdala-related fear and anxiety in
      two inbred rat lines differing in emotionality (RHA/Verh and RLA/Verh), and to
      relate the behaviour of the animals to neuronal types in different nuclei of the
      amygdala. The behavioural tests used were the motility test, elevated plus-maze
      and fear-potentiated startle response. The neurons investigated were
      immunoreactive for the anxiogenic peptide corticotropin-releasing factor (CRF
      ir), the anxiolytic peptide neuropeptide Y (NPY-ir), and the calcium-binding
      proteins parvalbumin (PARV-ir) and calbindin (CALB-ir). The NPY-ir, PARV-ir and
      CALB-ir neurons studied were subpopulations of GABAergic neurons. RLA/Verh rats,
      which showed a significant fear-potentiation of the acoustic startle response,
      had more CRF-ir projection neurons in the central nucleus of the amygdala. The
      same RLA/Verh rats were either less or equally anxious in the motility test
      (similar to open field) and elevated plus-maze as compared with RHA/Verh rats. In
      accordance with this behaviour, the RLA/Verh rats had more NPY-ir neurons in the
      lateral, and more PARV-ir neurons in basal nuclei of the amygdala than RHA/Verh
      rats, but no differences were detected in the number of CRF-ir and CALB-ir
      neurons of the basolateral complex. In conclusion, the RLA/Verh rats displayed an
      opposite behaviour in the fear-potentiated startle model and the exploratory
      tests measuring anxiety based on choice behaviour. Thus, the anxiogenic systems
      in the central nucleus and anxiolytic systems in the basolateral complex of the
      amygdala might be differentially involved in the fear-potentiated startle
      paradigm and exploratory tests in the Roman rat lines.

PMID- 11982632
TI  - Opposing effects of head position on sound localization in blind and sighted
      human subjects.
AB  - Up to now, there is an unsolved contradiction between the view that the
      development of an auditory spatial representation needs calibration by vision and
      the psychophysical demonstration of quite precise sound localization in early
      blind humans. The present study provides a link between these two competing
      conceptions. Two experiments were conducted with congenitally or early blind
      subjects and sighted controls. In the first experiment, subjects pointed with
      their head to actual sound sources located in the azimuthal plane. In the second
      experiment, lateralization of dichotic sound stimuli, presented via headphones,
      was investigated with variation of head-to-trunk position. The results showed
      opposing systematic errors of sound localization or lateralization, depending on
      head position, made by blind and sighted subjects. These differences suggest that
      audiomotor feedback replaces vision so as to calibrate auditory space in blind
      individuals. That is, in contrast to the widespread opinion of compensation of
      visual loss by a general sharpening of audition, compensatory plasticity in the
      blind may specifically be related to enhanced processing of proprioceptive and
      vestibular information with the auditory spatial input.

PMID- 11982633
TI  - Excitotoxic lesions of the rhinal cortex in the baboon differentially affect
      visual recognition memory, habit memory and spatial executive functions.
AB  - To specify the functional role of the rhinal cortex, baboons with bilateral
      excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of
      computerized memory and learning tasks. Preoperatively, they were trained to and
      then tested on a delayed nonmatching-to-sample (DNMS) task with trial-unique
      stimuli. Postoperatively, this visual recognition memory task was given twice. As
      compared to a sham-operated group, the RH group showed good retention of rule
      learning and were unimpaired on the Delay memory subtest. Performance on the List
      Length memory subtest was, however, severely impaired at both postoperative
      evaluations, with a significant negative correlation between cognitive
      performance and neuronal loss in rhinal areas. Visual habit memory and spatial
      working memory were assessed postoperatively only, using a concurrent
      discrimination learning task and both a delayed-response task (with a two- and
      four-location choice) and a delayed alternation task, respectively. The RH group
      was unimpaired on the first two tasks and was even faster than the controls in
      learning the delayed-response task with four locations. Finally, most RH baboons
      failed to learn the delayed alternation task within the limits of testing. These
      results indicate that neuronal loss in the rhinal cortex is sufficient to impair
      visual recognition memory, and extend the implication of this area to spatial
      executive functions. Furthermore, the observation of impaired recognition memory
      and executive processes with preserved procedural memory and retrograde memory
      suggests that damage to the rhinal cortex probably participates in the cognitive
      deficits typical of the early stages of Alzheimer's disease.

PMID- 11982634
TI  - The role of hippocampal dopamine receptors in prepulse inhibition.
AB  - Although it has long been realized that the hippocampal formation receives a
      projection from the midbrain dopaminergic cell groups and contains mRNA for all
      five dopamine receptors, the functional role of this dopaminergic projection has
      not been studied so far. The present study aimed to investigate the role of
      dopamine receptors in the dorsal CA1 area of the hippocampus in prepulse
      inhibition. The results show that local application of amphetamine reduced
      prepulse inhibition without affecting the baseline startle amplitude. This effect
      of amphetamine could be reversed by coadministration of the D1 antagonist
      SCH23390. Moreover, local application of the D1 agonist SKF81297 also disrupted
      prepulse inhibition without altering basal startle amplitude. These data clearly
      suggest that the hippocampal D1 receptor plays an important role in prepulse
      inhibition. The effects of amphetamine could not be reversed by coadministration
      of the D2 antagonist sulpiride. Interestingly, the D2/3 agonist quinpirole did
      reduce prepulse inhibition, again without affecting basal startle amplitude.
      Because quinpirole has a much higher affinity for the D3 receptor than does
      sulpiride, it is suggested that the D3 receptor might be involved in this effect.

PMID- 11982635
TI  - Timecourse of object-related neural activity in the primate prefrontal cortex
      during a short-term memory task.
AB  - We studied the timecourse of neural activity in the primate (Macacca mulatta)
      prefrontal (PF) cortex during an object delayed-matching-to-sample (DMS) task. To
      assess the effects of experience on this timecourse, we conducted the task using
      both novel and highly familiar objects. In addition, noise patterns containing no
      task-relevant information were used as samples on some trials. Comparison of
      average PF ensemble activity relative to baseline activity generated by objects
      and noise patterns revealed three distinct activity periods. (i) Sample onset
      elicited a transient sensory visual response. In this sensory period, novel
      objects elicited stronger average ensemble activity than both familiar objects
      and noise patterns. (ii) An intermediate period of elevated activity followed,
      which began before sample offset, and continued well into the delay period. In
      the intermediate period, activity was elevated for noise patterns and novel
      objects, but near baseline for familiar objects. (iii) Finally, after average
      ensemble activity reached baseline activity at the end of the intermediate
      period, a reactivation period occurred late in the delay. Experience had little
      effect during reactivation, where activity was elevated for both novel and
      familiar objects compared to noise patterns. We show that the ensemble average
      resembles the activity timecourse of many single prefrontal neurons. These
      results suggest that PF delay activity does not merely maintain recent sensory
      input, but is subject to more complex experience-dependent dynamics. This has
      implications for how delay activity is generated and maintained.

PMID- 11982636
TI  - Neural cells from primary human striatal xenografts migrate extensively in the
      adult rat CNS.
AB  - Primary neural cells do not appear to migrate significantly following
      transplantation into the adult rodent CNS, which is in contrast to expanded
      neural precursor cells where migration is well-documented. However, most
      transplant studies of primary neural tissue have been performed in an allograft
      situation in which it is difficult to identify graft-derived cells. We have,
      therefore, used a xenograft paradigm to investigate the potential for cells
      derived from grafts of primary human fetal striatal tissue (gestational age of 66
      72 days) to migrate following intrastriatal transplantation in an athymic adult
      rat model of Huntington's disease. The use of an antibody specific to human
      nuclear antigen enabled clear identification of graft-derived cells within the
      host brain, and specific neural phenotypes were determined using human-specific
      tau for neurons, glial fibrillary acidic protein for mature astrocytes and Ki67
      for proliferative cells. At 6 weeks, the graft mass was very dense with a high
      proliferative index, few cells had migrated away from the graft, and the cells
      that had differentiated both within and away from the graft were mainly neurons.
      In contrast, at 6 months, the graft core was dispersed significantly more and a
      large number of graft-derived cells had migrated throughout the brain as far
      rostral as the olfactory bulb and as caudal as the substantia nigra. Cells had
      differentiated into both neurons and astrocytes and the level of proliferation
      was significantly lower within the graft. These results demonstrate that primary
      neural xenografts contain proliferative cells that possess the ability to migrate
      and differentiate into both neurons and astrocytes, and suggest that these cells
      could contribute to normal graft function. This property may be a consequence of
      the xenograft situation and could potentially be exploited to provide the
      opportunity to target regions of distant pathology in neurodegenerative diseases
      using xenotransplantation of embryonic neural tissue.

PMID- 11982637
TI  - Classical eyeblink conditioning in decerebrate guinea pigs.
AB  - A decerebrate guinea pig preparation was used to test the hypothesis that
      brainstem-cerebellar circuitry is sufficient for classical delay eyeblink
      conditioning. Delay conditioning was carried out using a tone conditioned
      stimulus (CS) paired with a co-terminating, periorbital shock unconditioned
      stimulus (US). Decerebrate animals readily acquired the conditioned response
      (CR), while pseudoconditioning yielded no signs of learning. When a longer tone
      CS was used, the learning became slower. These CRs were adaptive and
      appropriately timed relative to the US. Subsequent CS-alone trials caused
      extinction of the CR. These characteristics of the eyeblink conditioning were
      similar to those reported previously in various species, suggesting that the
      cerebellum and brainstem are sufficient for this type of learning.

PMID- 11982638
TI  - Pyoderma gangrenosum: a report of 21 cases.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon, destructive, cutaneous
      ulceration, belonging to the neutrophilic disease spectrum. It is associated with
      systemic disease in 50% of cases. METHODS: We report a retrospective study of 21
      cases of PG. All cases studied fulfilled the following criteria: (i) clinical
      features of PG; (ii) histopathology consistent with a diagnosis of PG, and
      excluding other specific dermatoses. RESULTS: The average age of our patients was
      41.8 years. The male to female ratio was 1.1. The typical ulcerative variant was
      found in 17 patients, bullous PG in two patients, and the granulomatous variant
      in two patients. Sixty-two per cent of our patients had lesions on their lower
      legs. Two patients had neutrophilic pulmonary involvement concurrent with the
      ulcers. An association with other internal diseases was noted in 12 patients.
      Histopathologic study showed vasculitis in 13 patients. Of these, 11 were
      leukocytoclastic and the others predominantly lymphocytic. CONCLUSIONS: PG is a
      rare disease, with the ulcerative variant being most frequent. The lower legs are
      the most commonly affected sites. The recurrence rate in our study was about 46%
      regardless of the treatment prescribed. Pulmonary involvement was fatal in two
      patients.

PMID- 11982639
TI  - The widespread use of skin lightening creams in Senegal: a persistent public
      health problem in West Africa.
AB  - BACKGROUND: The use of skin lightening creams is common in the female population
      of some African countries. The long-term use of certain products for several
      months to years may cause cutaneous adverse effects. METHODS: From 1992 to 1993,
      we conducted an epidemiologic and clinical study in Dakar, Senegal. Women were
      questioned about the use of skin lightening creams and examined for potential
      adverse skin reactions. Six hundred and eighty-five Senegalese women participated
      in the study. RESULTS: Twenty-six per cent of women were using skin lightening
      creams at the time and 36% had used them at some time. The most common products
      used were hydroquinone and corticosteroids, but 25% of women had used products of
      unknown composition. Seventy-five per cent of women using such creams showed
      cutaneous adverse effects. Facial acne was the most common adverse effect.
      CONCLUSIONS: A major part of the female adult population of Senegal used skin
      lightening creams. The long-term use of these creams is responsible for a high
      rate of cutaneous adverse effects. This practice has also been reported in other
      countries from sub-Saharan Africa and suggests a widespread use in the African
      population.

PMID- 11982640
TI  - Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed
      Leishmania (Leishmania) amazonensis vaccine plus antimonial.
AB  - BACKGROUND: Leishmaniasis is endemic in 88 countries in the world, and 350
      million individuals are at risk of acquiring the disease. Treatment for American
      cutaneous leishmaniasis (ACL) is long, expensive, and associated with important
      side-effects. METHODS: In this double-blind, placebo-controlled study, we treated
      102 patients with ACL using either a combination of a single-strain Leishmania
      amazonensis killed promastigote vaccine plus a half dose of meglumine
      antimoniate, or placebo plus the same half dose regimen of meglumine antimoniate,
      in 10-day series followed by 10-day intervals. RESULTS: Of the 47 patients in the
      experimental arm, 47 (100%) were cured after four series of treatment, compared
      to four of 49 (8.2%) in the control group (P < 0.0001). Six patients were lost to
      follow-up. CONCLUSIONS: The combination of a single-strain Leishmania
      (Leishmania) amazonensis killed promastigote vaccine with a half dose regimen of
      antimonial is highly effective for the treatment of ACL.

PMID- 11982641
TI  - HLA-class 1 and class 2 antigens in Turkish patients with pemphigus.
AB  - BACKGROUND: Pemphigus is an autoimmune disease which is more frequently seen in
      certain ethnic groups such as Jews. It is thought that exogenous factors may
      induce pemphigus in genetically predisposed individuals. Recent reports on HLA
      antigens indicate an increased frequency of HLA-class II antigens particularly
      HLA-DR4 among Jewish patients. Herein we investigated the antigen frequencies of
      HLA-A, B, C, HLA-DR and DQ in Turkish patients with pemphigus. METHODS: HLA class
      I and II antigens were typed by microdroplet lymphocyte cytotoxicity test in 33
      patients with pemphigus and 100 healthy individuals. RESULTS: HLA-B35, B44, CW4,
      DR4, DR14, DQ8 and DQ4 antigens were significantly high in the study group
      whereas HLA-DR11, DQ7 and DQ2 antigens were high among the controls. The most
      striking differences were observed in HLA class II antigens. HLA DR14-DQ8 and HLA
      B35-DR14 haplotypes were the most frequently observed ones in the study group.
      CONCLUSIONS: We postulate that HLA-B35, B44, CW4, DR4, DR14, DQ4 and DQ8 antigens
      may be responsible for susceptibility to pemphigus while HLA-DR11, DQ7 and DQ2
      antigens may have a protective role in the Turkish population.

PMID- 11982642
TI  - Treatment of arsenical keratosis and Bowen's disease with acitretin.
AB  - BACKGROUND: Long-term exposure to arsenic is associated with the development of
      arsenical keratosis, Bowen's disease, squamous cell carcinoma, and basal cell
      carcinoma. The efficacy of acitretin therapy was examined in two patients with
      cutaneous arsenical neoplasms. METHODS: Lipid profile, hematological and liver
      function tests were performed regularly during the therapy at monthly intervals.
      RESULTS: After the third month of treatment, improvement of lesions of arsenical
      keratosis and Bowen's disease were observed in both patients. For the first
      patient who received 1 mg/kg daily acitretin for 10 months nearly total clearing
      was obtained at the end of therapy. The second patient discontinued the treatment
      after a period of 5 months because of symptomatic side-effects. During therapy no
      new lesions and no laboratory side-effects were observed in either patient.
      CONCLUSIONS: Although these results need to be confirmed by larger, long-term
      trials, it appears that acitretin is effective in the treatment of Bowen's
      disease related with arsenic, as well as arsenical keratosis.

PMID- 11982643
TI  - An ultrastuctural study of hair fiber damage and restoration following treatment
      with permanent hair dye.
AB  - INTRODUCTION: Hair fibers are comprised of non-nucleated keratinocytes and are
      biologically dead. Clinical damage to the hair shaft occurs with the application
      of hair dye. Whether this damage can be repaired and the time frame involved is
      of interest and may help to determine the optimal interval between repeat
      applications. AIMS AND METHODS: Ultrastructural changes of hair shafts after
      application of permanent hair dye were observed sequentially in a 26-year-old
      woman. The dye contained p-phenylenediamine, m-aminophenol, resorcin and hydrogen
      peroxide as an oxidizer. Scanning and transmission electron microscopy was
      performed immediately before application of the hair dye and again at 30 min, 1
      h, 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks.
      RESULTS: The hair showed cuticular swelling with focal degeneration. In some
      places there was exposure of the hair cortex due to extensive cuticular
      detachment. There were many holes of various size in the endocuticle, small focal
      lacunae along the intercellular space and an ill-defined A-layer especially
      beneath the area of cuticular detachment. The exocuticle appeared normal. The
      findings were most dramatic in the 6 h and 1 day specimens and tended to improve
      gradually thereafter. The 8 week specimen showed near complete restoration of the
      hair cuticle and return to the precoloring state. CONCLUSION: Hair returns to its
      precoloring state and this requires 8 weeks.

PMID- 11982644
TI  - Microcirculatory changes in travelers to a tropical country.
AB  - BACKGROUND: Travelers to tropical areas seem to be affected by nonhealing leg
      ulcers more frequently. One of the factors that can affect wound healing in a
      negative manner is leg edema. This study was performed to determine whether there
      is increased leg edema in travelers to tropical areas. METHOD: In this study, we
      measured the capillary filtration rate (CFR) of the lower leg by strain gauge
      plethysmography, as a measure of leg edema, on location in Surinam. Three groups
      were included: A, travelers in the first few weeks after arrival; B, travelers
      who had stayed in the tropics for a minimum of 2 months; C, native inhabitants.
      RESULTS: The mean CFR (mL/100 mL tissue/min) was significantly higher in group A
      than in groups B and C; the difference between groups B and C was not significant
      (group A 0.05 mL/100 mL tissue/min (standard deviation (SD), 0.03) vs. group B
      0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01, and vs. group C 0.02 mL/100 mL
      tissue/min (SD, 0.02), P = 0.01). CONCLUSIONS: Travelers to tropical areas are
      affected by increased CFR in the first few weeks after arrival. A prolonged stay
      leads to the normalization of the CFR. Compression therapy is recommended for
      travelers to the tropics.

PMID- 11982645
TI  - Peculiar unilateral fixed drug eruption of the breast.
AB  - BACKGROUND: Fixed drug eruption (FDE) is a common cutaneous disorder which
      develops within hours of taking the offending drug and recurs at the same site
      with subsequent exposure to the same drug. Non-steroidal anti-inflammatory drugs
      (NSAIDs) are common offending drugs. METHODS: A 14-year-old girl initially
      presented with a 1-year history of a recurrent reddish-brown plaque around her
      right areola. The lesion became pruritic and raised during menses, and subsided
      during the remainder of her menstrual cycle with the exception of persistent
      residual hyperpigmentation. The patient had a pattern of naproxen use during
      menses for dysmenorrhea. RESULTS: The skin biopsy specimen revealed focal bullae
      formation and scattered necrotic keratinocytes in epidermis, hydropic
      degeneration of the basal cell layer, pigmentary incontinence and a perivascular
      infiltrate composed of lymphocytes and eosinophils. These changes confirmed the
      diagnosis of fixed drug eruption. CONCLUSION: Fixed drug eruption to nonsteroidal
      anti-inflammatory drugs is common. However, FDE due to naproxen, one of the
      NSAIDs, is rarely reported. We describe an unusual case of FDE, which recurred at
      each menses.

PMID- 11982646
TI  - Malignant melanoma mortality rates in Chile (1988-98).
AB  - BACKGROUND: Malignant melanoma (MM) mortality has increased in the Caucasian
      population many fold over the past several decades. In this study, we analyzed
      the Chilean-specific, age-adjusted MM mortality rates per 100,000 population
      during the decade 1988-98 in order to establish changes in that period. METHODS:
      We analyzed all death certificates from the Chilean Death Registry Office (1988
      98) and retrieved the deaths attributed to MM. The data were categorized
      according to sex and age group. The annual age-adjusted and sex-specific rates of
      MM mortality per 100,000 population were calculated. RESULTS: Chilean MM
      mortality rates increased by 14% between 1988 and 1998. The relative risk for
      males vs. females was 1.3 with a tendency to rise, showing an increase of 30%.
      The relative risk of dying from MM in Chile increased linearly with age. An
      individual of 75 years or older had a 44.24 times greater risk of dying of MM
      than an individual in the 0-44-year age group. The rates in the > 75-year age
      group also showed a tendency to rise over the decade, with an increase of 64%
      (1988-98). CONCLUSIONS: The Chilean MM mortality rates are lower than the world
      standardized rates. The total Chilean MM mortality rates showed an increase over
      the decade 1988-98, mainly due to MM mortality in males. The MM mortality in
      Chilean females was lower than that in males, and was unchanged over the decade;
      this is in agreement with the results reported in other countries. This is one of
      the first studies of MM mortality in the Chilean population. The results are
      important when the geographic location of Chile is considered.

PMID- 11982647
TI  - Treatment of cutaneous T-cell lymphoma with alitretinoin gel.

PMID- 11982648
TI  - Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular
      episcleritis and polyneuropathy.

PMID- 11982649
TI  - Cutaneous HSV-2 infection with serial recurrences at multiple sites.

PMID- 11982650
TI  - Mucin-poor follicular mycosis fungoides.

PMID- 11982651
TI  - Erythema nodosum associated with sporotrichosis.

PMID- 11982652
TI  - Sudden onset of melanuria in a patient with metastatic melanoma and toxic
      epidermal necrolysis.

PMID- 11982653
TI  - Faun tail: a rare cutaneous stigma of spinal dysraphism.

PMID- 11982654
TI  - Anticonvulsant hypersensitivity syndrome and acute neurotrauma.

PMID- 11982655
TI  - The Sixth Asian Dermatological Congress.

PMID- 11982658
TI  - HIV infection: treatment outcomes in older and younger adults.
AB  - OBJECTIVES: To determine the effect of antiretroviral therapy (ART) on the
      immunological and virological outcomes of older human immunodeficiency virus
      (HIV)-infected patients compared with younger HIV-infected patients. DESIGN:
      Matched (1:2) retrospective case-control study (1993-1999). SETTING: Duke
      University Infectious Diseases Clinic. PARTICIPANTS: One hundred one older
      patients, mean age 56.7 (range 50-79) and 202 younger patients, mean age 32.8
      (range 21-39). Patients were matched on baseline CD4+ cell count and date of
      clinic entry. MEASUREMENTS: The virological and immunological outcomes were viral
      suppression (HIV ribonucleic acid (RNA) level < or =400 copies/ml) and change in
      CD4+ cell count. To estimate differences in antiretroviral drug exposure, the
      percentage of patients on ART overall and by drug class was compared. To assess
      antiretroviral drug exposure further, the percentage of patients having
      interruptions in ART was compared. RESULTS: The older and younger groups had
      similar baseline CD4+ cell counts (332 vs 306 cells/mm3; P =.31) and similar
      increases in CD4+ cell counts (+3.47 vs +4.60 cells/mm3/month; P =.37) over a
      mean +/- standard deviation of 2.4 +/- 1.7 years of follow-up. The older group
      had a higher percentage of patients with current plasma HIV RNA levels less than
      400 (46% vs 34%; P =.05). The groups had similar rates of non-nucleoside reverse
      transcriptase, nucleoside reverse transcriptase, and protease inhibitor use. The
      older group had fewer interruptions in ART than the younger group (11% vs 26%; P
      =.01). CONCLUSIONS: Older HIV-infected patients responded well to ART, with a
      significantly greater percentage achieving a current plasma HIV RNA below
      detectable limits. Older patients experienced similar increases in CD4+ cell
      count as younger matched controls. Older patients were less likely to interrupt
      ART, which suggests better adherence and/or tolerance and may explain the higher
      rate of HIV RNA suppression.

PMID- 11982659
TI  - Use of oseltamivir during influenza outbreaks in Ontario nursing homes, 1999
      2000.
AB  - OBJECTIVES: To describe the experience of Ontario long-term care facilities that
      used oseltamivir during influenza outbreaks in 1999/2000. DESIGN: Case series.
      SETTING: Ten Ontario long-term care facilities for older people and their
      residents. PARTICIPANTS: Older residents of long-term care facilities.
      INTERVENTION: Oseltamivir for treatment or prophylaxis during 11 influenza
      outbreaks in 1999/2000. MEASUREMENTS: Control of outbreaks; pneumonia,
      hospitalization, and death complicating acute influenza. RESULTS: All outbreaks
      were due to influenza A//H3N2/Sydney/05/97. One facility elected to use
      oseltamivir for treatment and amantadine for prophylaxis. The remaining nine
      facilities (10 outbreaks) recommended oseltamivir for treatment and prophylaxis
      (after amantadine failure in five and as primary prophylaxis in five). Use of
      oseltamivir was associated with termination of the outbreak in all eight
      evaluable outbreaks. Overall, 178/185 (96%) case-residents met the case
      definition of influenza and had complete data for evaluation. Of these, 63 (35%)
      were treated with antibiotics, 37 (21%) were diagnosed with pneumonia, 19 (11%)
      were hospitalized, and 16 (9%) died. Compared with residents receiving no therapy
      or who became ill while taking amantadine, residents who received oseltamivir
      within 48 hours of the onset of symptoms were less likely to be prescribed
      antibiotics, to be hospitalized, or to die (P <.05 for each outcome). These
      differences persisted and remained statistically significant when corrected for
      influenza immunization status. A total of 730 residents received oseltamivir
      prophylaxis for a median of 9 days (range 5-12). Of these, side effects were
      identified in 30 (4.1%), the most common being diarrhea (12 residents, 1.6%),
      cough (5, 0.7%), confusion (4, 0.5%) and nausea (4, 0.5%). CONCLUSIONS:
      Oseltamivir is safe and appears to be effective when used as treatment or
      prophylaxis to control outbreaks of influenza in older nursing home residents.

PMID- 11982660
TI  - Failure of timed bright light exposure to alleviate age-related sleep maintenance
      insomnia.
AB  - OBJECTIVES: To determine whether a twice-weekly maintenance schedule of evening
      bright light exposure is effective in alleviating sleep maintenance insomnia on a
      long-term basis, after the establishment of a more favorable phase relationship
      between the core body temperature (CBT) rhythm and sleep. DESIGN: Subjects
      underwent light treatment while living at home. Eleven to 13 consecutive days of
      acute light treatment (active) were followed by a 3-month maintenance light
      treatment period (active or control). Subjects completed five laboratory
      sessions: before and after the acute phase and once a month during the
      maintenance period. SETTING: Sleep laboratory and subjects' homes. PARTICIPANTS:
      Fifteen older subjects (seven women, eight men; aged 63-84) with chronic (>1
      year) complaints of sleep maintenance insomnia. INTERVENTIONS: During the acute
      phase, all participants were exposed to evening bright light (approximately 9:00
      p.m. to 11:00 p.m.;>4,000 lux). During the maintenance phase, light treatment was
      reduced to a twice-weekly schedule, in which the active group received bright
      light from approximately 9:00 p.m. to 11:00 p.m. and the control group received
      bright light from 3:00 p.m. to 5:00 p.m. MEASUREMENTS: During each laboratory
      session, polysomnographic sleep and CBT were measured. RESULTS: Bright light
      exposure during the acute treatment resulted in an average phase delay in the
      temperature rhythm (Tmin) of 94 minutes. Sleep quality was not improved. No
      significant differences between active and control subjects were found during the
      maintenance phase; in both groups, Tmin gradually reverted to the baseline phase
      position, and sleep efficiency remained unchanged. CONCLUSIONS: Although a
      significant phase shift in CBT was achieved during the acute treatment phase, no
      improvement in sleep quality was observed. Twice-weekly light exposure was not
      effective in maintaining the circadian phase shift over the subsequent 3 months.
      Issues of compliance and alternate etiologies for the sleep maintenance insomnia
      are discussed.

PMID- 11982661
TI  - Screening for cobalamin deficiency in geriatric outpatients: prevalence and
      influence of synthetic cobalamin intake.
AB  - OBJECTIVES: To describe the prevalence of cobalamin (Cbl) deficiency in older
      adult outpatients and to determine whether regular intake of a synthetic source
      of cobalamin confers protection against Cbl deficiency. DESIGN: Cross-sectional
      study. SETTING: Two university-affiliated geriatric medicine outpatient clinics.
      PARTICIPANTS: Three hundred fifteen older adults (age range 65-100) without a
      history of previously diagnosed or treated Cbl deficiency, severe anemia, or a
      life-threatening illness. MEASUREMENTS: Detailed information on total synthetic
      Cbl intake (from vitamins, fortified cereal, and supplemental nutritional formula
      sources) and laboratory measures of serum Cbl, metabolite panel (serum
      methylmalonic acid, homocysteine, cystathionine, and 2-methylcitric acid),
      complete blood count, and serum creatinine levels. RESULTS: Cbl deficiency (serum
      Cbl < or =300 pg/mL and methylmalonic acid (MMA)>271 nmol/L) was found in 13% of
      screened patients. Forty-six percent of screened patients reported regularly
      taking a source of synthetic Cbl. Serum Cbl correlated with synthetic Cbl intake,
      and patients regularly taking synthetic Cbl were significantly less likely to be
      Cbl deficient than persons not taking supplemental Cbl (8% vs 17%, P =.02).
      CONCLUSION: Regular use of a multivitamin/synthetic Cbl source confers some
      degree of protection against Cbl deficiency in older adults. The relatively high
      prevalence rates and benefit of synthetic Cbl intake in this study reinforce
      recommendations that older adults should be screened for Cbl deficiency and
      should incorporate synthetic sources of Cbl as part of a balanced diet.
      Appropriate screening intervals and the optimal dose of supplemental Cbl to
      prevent Cbl deficiency remains to be determined.

PMID- 11982662
TI  - Serum albumin concentration and clinical assessments of nutritional status in
      hospitalized older people: different sides of different coins?
AB  - OBJECTIVES: Malnutrition is common in hospitalized older people, and some have
      advocated routine nutritional screening. Serum albumin and clinically based
      measures such as the Subjective Global Assessment (SGA) are two potential methods
      of assessing nutritional status in hospitalized older people. Although both
      measures are strongly associated with prognosis, it is not clear whether they
      measure similar or different clinical constructs. Our goal was to assess the
      degree of clinical concordance between these measures. DESIGN: Cross-sectional
      study. SETTING: The inpatient medical service of a university teaching hospital.
      PARTICIPANTS: Three hundred eleven older (aged > or =70) patients. MEASUREMENTS:
      We independently measured serum albumin and performed the SGA on 311 older
      medical patients (aged > or =70) shortly after hospital admission. The SGA
      classified patients as well nourished, moderately malnourished (generally 5%
      weight loss with mild examination findings), or severely malnourished (generally
      >10% weight loss with marked findings) based on findings from a directed history
      and examination. We compared the distribution of clinical rating in patients with
      differing albumin levels and examined diagnostic test characteristics of albumin
      as a predictor of malnutrition as diagnosed on clinical examination. RESULTS: The
      mean age of subjects was 79.9; 64% were women, 42% were African American.
      Discordance between albumin and the SGA was common. For example, 38% of patients
      with albumin levels of 4.0 g/dL or higher were at least moderately malnourished
      on the SGA, whereas 28% of patients with albumin levels lower than 3.0 g/dL were
      rated as well nourished. No choice of albumin level was associated with
      simultaneously acceptable sensitivity and specificity as a predictor of SGA
      ratings. The area under the receiver operating characteristic curve for albumin
      level as a predictor of SGA rating was 0.58, suggesting that the ability of
      either measure to predict the other measure is only marginally better than
      chance. CONCLUSIONS: Albumin levels and clinical assessments, two possible
      measures of nutritional status in hospitalized older people, are often
      discordant. To some extent, this reflects limitations in both measures as markers
      of nutritional status. However, it also demonstrates that, in this population,
      albumin and clinical assessments of nutritional status reflect fundamentally
      different clinical processes.

PMID- 11982663
TI  - Peripheral blood markers of inflammation predict mortality and functional decline
      in high-functioning community-dwelling older persons.
AB  - OBJECTIVES: Several peripheral blood markers of inflammation have demonstrated
      prognostic ability, but the value of combining multiple markers as a measure of
      inflammatory burden remains unknown. The objective of this study was to determine
      the prognostic value of combining four peripheral blood measures of inflammation
      in healthy older persons. DESIGN: Inception cohort study with 7 years of follow
      up. SETTING: Three communities. PARTICIPANTS: Eight hundred seventy high
      functioning subjects aged 70 to 79 who had serum albumin, cholesterol,
      interleukin (IL)-6, and C-reactive protein (CRP) levels measured at baseline.
      MEASUREMENTS: Three- and 7-year mortality and Rosow- Breslau functional decline.
      RESULTS: A summary score was created that assigned one point each for the
      following blood levels: albumin <3.8 g/dL, cholesterol <170 mg/dL (bottom
      decile), IL-6>3.8 pg/mL (top tertile), and CRP>2.65 mg/L (top tertile). By 3
      years, 6% of subjects had died, and, by 7 years, 23% had died. In subjects with
      three or four markers of inflammation, the adjusted odds ratios (AORs) for 3- and
      7-year mortality were 6.6 and 3.2, respectively, compared with those who had no
      abnormal markers. Subjects with one or two markers were at more moderate and
      statistically insignificant increased risk of 3- and 7-year mortality with AORs
      of 1.5 and 1.3, respectively. The risks for functional decline at 3- and 7-years
      were generally small (AOR = 1.1-1.9) and not statistically significant.
      CONCLUSIONS: In high-functioning older persons, a measure of inflammation can
      identify those at a much higher risk of mortality and a possibly higher risk of
      functional decline. Whether therapies directed at reducing inflammation can
      attenuate such risk remains to be determined.

PMID- 11982664
TI  - Wheelchair users are not necessarily wheelchair bound.
AB  - OBJECTIVES: To determine the patterns of wheelchair use in terms of locations of
      use, whether wheelchair use in one location was related to wheelchair use in
      other locations, and factors associated with wheelchair use in different
      locations. DESIGN: Longitudinal cohort study. SETTING: Patients prescribed
      wheelchairs by clinicians at one of two teaching hospitals (one Veterans Affairs
      hospital and one private hospital). PARTICIPANTS: One hundred fifty-three
      consecutive persons who were prescribed a new wheelchair, resided in the
      community, had a Short Portable Mental Status Questionnaire score of greater than
      six out of 10, and who could be interviewed within 7 to 21 days of receiving the
      wheelchair. MEASUREMENTS: Patient, wheelchair, and environmental characteristics
      and self-reported wheelchair use in life spaces. RESULTS: Wheelchair use in the
      24 hours before the interview was inconsistent across life spaces. The
      correlation between wheelchair use in the bath and in the kitchen was 0.66,
      between locations near and far from home was -0.08, and between locations in the
      home and outside the home was 0.08. Predictors of wheelchair use in the home were
      using help from another person to propel the wheelchair (odds ratio (OR) = 0.14,
      95% confidence interval (CI) = 0.04-0.45), the number of impairments (OR = 0.80,
      95% CI = 0.67-0.96), a report that the wheelchair did not meet the subject's
      needs (OR = 3.71, 95% CI = 1.27-10.81), and having adapted the home to
      accommodate the wheelchair (OR = 3.75, 95% CI = 1.47-8.18). Having adapted the
      home was also positively associated with use of the wheelchair in areas near the
      home (OR = 4.77, 95% CI = 1.94-11.71). The only factor associated with wheelchair
      use in distant locations was older age (OR = 0.62, 95% CI = 0.46-0.83 per 10-year
      increment). CONCLUSIONS: Personal factors (e.g., using help to propel the
      wheelchair) and environmental factors (e.g., home adaptations to accommodate the
      wheelchair) influenced wheelchair use. In addition, wheelchair use, and the
      factors influencing wheelchair use, differed by location. Wheelchair users appear
      to use their wheelchairs selectively, depending on their physical needs and the
      constraints of their environment.

PMID- 11982665
TI  - High-velocity resistance training increases skeletal muscle peak power in older
      women.
AB  - OBJECTIVES: Peak power declines more precipitously than strength with advancing
      age and is a reliable measure of impairment and a strong predictor of functional
      performance. We tested the hypothesis that a high-velocity resistance-training
      program (HI) would increase muscle power more than a traditional low-velocity
      resistance-training program (LO). DESIGN: Randomized controlled trial. SETTING:
      University-based human physiology laboratory. PARTICIPANTS: Thirty women with
      self-reported dis-ability (aged 73 + 1, body mass index 30.1 + 1.1 kg/mn).
      INTERVENTION: We conducted a randomized trial comparing changes in skeletal
      muscle power and strength after 16 weeks of HI or LO. Training was performed
      three times per week, and subjects completed three sets (8-10 repetitions) of leg
      press (LP) and knee extension (KE) exercises at 70% of the one-repetition maximum
      (IRM). MEASUREMENTS: One-repetition maximum (1 RM) and peak power for KE and LP.
      RESULTS: LP and KE relative training force and total work were similar between
      groups (P > .05). However, HI generated significantly higher power during
      training sessions than LO for LP (3.7-fold greater, P < .001) and KE (2.1-fold
      greater, P < .001). Although LP and KE 1RM muscle strength increased similarly in
      both groups asa result of the training (P < .001), LP peak power increased
      significantly more in HI than in LO (267 W vs 139 W, P < .001). Furthermore, HI
      resulted in a significantly greater improvement in LP power at 40%, 50%, 60%,70%,
      80%, and 90% of the 1 RM than did LO (P <.05). CONCLUSIONS: HI improved 1RM
      strength similarly and was more effective in improving peak power than was
      traditional LO in older women. Improvements in lower extremity peak power may
      exert a greater influence on age-associated reductions in physical functioning
      than other exercise interventions.

PMID- 11982666
TI  - Weighted stair climbing in mobility-limited older people: a pilot study.
AB  - OBJECTIVES: To evaluate weighted stair climbing exercise (SCE) as a means of
      increasing lower extremity muscle power in mobility-limited older people. DESIGN:
      Single-blinded, randomized controlled pilot study. SETTING: Human physiology
      laboratory of a metropolitan university. PARTICIPANTS: Forty-five community
      dwelling people aged 65 and older who had baseline mobility limitations
      manifested by scores of 11 or lower on the Short Physical Performance Battery
      (SPPB). INTERVENTIONS: Subjects were randomized into one of two 12-week exercise
      programs. The intervention group (SCE) (n = 23) ascended and descended stairs, at
      a set pace, while wearing a weighted vest. The control group (WALK) (n = 22)
      participated in a standardized walking program. MEASUREMENTS: Primary and
      secondary outcomes included measures of muscle power and strength, submaximal
      aerobic capacity, and physical performance. RESULTS: SCE produced 17% improvement
      in double leg press peak power in comparison with WALK (P =.013) and significant
      improvement in stair climbing power from baseline (12%). Improvement in
      submaximal aerobic performance was equivalent for both groups. Although not
      statistically significant, effect size estimates suggest that SCE can potentially
      influence knee extension power and strength. Stair climb time was improved in
      both groups, whereas SCE produced significant improvements from baseline SPPB
      score in a subcohort of participants. CONCLUSIONS: These findings suggest that
      SCE maybe a useful component of a home exercise program designed to enhance lower
      extremity muscle power, aerobic capacity, and functional performance. Further
      investigation is needed involving larger sample sizes and direct comparisons with
      other forms of resistance training.

PMID- 11982667
TI  - Musculoskeletal pain and risk for falls in older disabled women living in the
      community.
AB  - OBJECTIVES: To determine whether musculoskeletal pain increased risk for falls in
      older women with disabilities. DESIGN: Prospective population-based cohort study.
      SETTING: The city and county of the eastern area of Baltimore. PARTICIPANTS: One
      thousand two women aged 65 and older, participants in the Women's Health and
      Aging Study, representing the one-third of older women who were living at home
      with disabilities, followed semiannually for 3 years beginning in 1991.
      MEASUREMENTS: Pain was categorized into four groups according to severity and
      location. Widespread pain was defined as pain in the upper and lower extremities
      and in the axial skeletal region, with moderate to severe pain in at least one
      region (> or = 4 on a 10-point numeric rating scale, 10 = excruciating pain).
      Moderate to severe lower extremity pain that did not meet criteria for widespread
      pain was the next category. The reference category was no pain or mild pain in
      one site. The additional category of "other pain" was pain that did not fit into
      the other three groups. The occurrence of falls and fall-related injuries were
      assessed at each interview. RESULTS: Of the 940 women who participated in at
      least one follow-up examination, 39% fell in first year; of the survivors, 36%
      fell in Year 2, and 39% in Year 3. After adjusting for several major risk factors
      for falls, women with widespread pain had an increased likelihood of falling
      during follow-up (adjusted odds ratio (AOR) = 1.66, 95% confidence interval (CI)
      = 1.25-2.21) compared with those with no or mild pain in only one musculoskeletal
      site. Women who had other musculoskeletal pain but not widespread pain or lower
      extremity pain also had an increased risk of falls (AOR = 1.36, 95% CI = 1.02
      1.82). Among women with musculoskeletal pain, risk for falls was lower in those
      who used daily analgesic medication. Risk for recurrent falls and self-reported
      fractures due to falls was also elevated in women with musculoskeletal pain, most
      consistently in women with widespread pain. CONCLUSIONS: Musculoskeletal pain,
      particularly widespread pain, is a substantial risk factor for falls in older
      women with disabilities. These findings add an important dimension to our
      understanding of the multifactorial processes leading to falls in older persons.

PMID- 11982668
TI  - Predictors of rehabilitation outcomes in frail patients treated in a geriatric
      hospital.
AB  - OBJECTIVES: To evaluate the effect of medical indicators of health status on
      functional gain during rehabilitation of frail older patients. DESIGN:
      Observational study. SETTING: A hospital geriatric rehabilitation department
      (Catholic University of Rome). PARTICIPANTS: Two hundred forty-four older
      patients admitted consecutively for rehabilitation after acute illnesses between
      March 1999 and June 2000. MEASUREMENTS: Patients were evaluated with the Minimum
      Data Set for Post-Acute Care (MDS-PAC) assessment form soon after the admission
      and every 2 weeks thereafter. Two summary scales based on MDS-PAC items are
      designed to describe the performance in personal activities of daily living
      (ADLs) and the level of cognitive function (Cognitive Performance Scale). To
      identify predictors of functional recovery, we constructed a multiple logistic
      regression model having as a dependent variable the improvement of one or more
      points in the ADL scale. RESULTS: Patients aged 85 and older with cognitive or
      sensory impairment were less likely to significantly improve physical functioning
      after an intensive rehabilitation program. However, the cognitive impairment was
      the only "negative" factor that remained significant in a multivariable model
      (odds ratio = 0.36, 95% confidence interval = 0.14-0.92) after adjusting for
      several potential negative predictors. CONCLUSIONS: The results of the present
      study document that severe cognitive impairment may be considered a negative
      predictor of functional recovery after a period of intensive rehabilitation.
      However, the effectiveness of such a rehabilitation program in patients with
      dementia is controversial. Additional studies are necessary to better clarify the
      effect of cognitive impairment on the potential recovery of the older subjects
      after a period of rehabilitation and whether this is influenced by different
      pathologies.

PMID- 11982669
TI  - Excess mortality or institutionalization after hip fracture: men are at greater
      risk than women.
AB  - OBJECTIVES: To assess 2-year excess mortality or institutionalization risk
      associated with hip fracture in community-dwelling people aged 60 and over.
      DESIGN: Cohort study. SETTING: Auckland, New Zealand, from July 1991 to February
      1996. PARTICIPANTS: Five hundred sixty-five community-dwelling older people
      recently hospitalized with a hip fracture and 782 randomly selected controls,
      frequency matched for age and gender, living in the same catchment area as the
      cases. MEASUREMENTS: Two-year mortality or institutionalization status. RESULTS:
      Over half (52.1%) of male hip fracture cases and 12.4% of male controls were dead
      or institutionalized, compared with 39.2% of female hip fracture cases and 19.7%
      of female controls. The odds ratio, adjusted for baseline demographic
      characteristics, medical status, and physical function, for death or
      institutionalization was 6.89 (95% confidence interval (CI) = 2.75-17.27) for men
      and 1.48 (95% CI = 1.02-2.19) for women. CONCLUSIONS: For both men and women who
      incur a hip fracture, the risks of dying or being institutionalized within 2
      years are higher than for their peers. The independent effect of hip fracture on
      this outcome was significantly greater for men than women. The marked influences
      of prefracture health status, physical limitations, and gender on outcome have
      important implications for preventative strategies.

PMID- 11982670
TI  - The role of smoking and other modifiable lifestyle risk factors in maintaining
      and restoring lower body mobility in middle-aged and older Americans: results
      from the HRS and AHEAD. Health and Retirement Study. Asset and Health Dynamics
      Among the Oldest Old.
AB  - OBJECTIVES: To analyze the effect of smoking, smoking cessation, and other
      modifiable risk factors on mobility in middle-aged and older Americans. DESIGN:
      Panel study; secondary data analysis. SETTING: United States (national sample).
      PARTICIPANTS: The Health and Retirement Study (HRS) includes data on 12,652
      Americans aged 50 to 61 in four waves (1992-1998). The Asset and Health Dynamics
      Among the Oldest Old (AHEAD) survey followed 8,124 community-dwelling people aged
      70 years and older in three waves (1993-1998). MEASUREMENTS: The relationships
      between the primary outcome measure, lower body mobility (ability to walk several
      blocks and walk up one flight of stairs without difficulty), and smoking,
      exercise (HRS only), body mass index (BMI), and alcohol use were estimated in
      bivariate and multivariate analyses. RESULTS: Not smoking was strongly positively
      related to mobility, and the relative effects were similar in both panels. Among
      those with impaired mobility at baseline, not smoking was also strongly related
      to recovery. In the middle aged, there were consistent dose-response
      relationships between amount smoked and impaired mobility. Fifteen years after
      quitting, the risk of impaired mobility returned to that of never smokers. There
      was also a strong dose-response relationship between level of exercise and
      mobility. Inverted U-shaped relationships with mobility were observed for BMI and
      alcohol consumption. CONCLUSIONS: The relationships between not smoking and lower
      body mobility in middle-aged and older Americans are strong and consistent.
      Interventions aimed at reducing smoking have the potential to preserve mobility
      and thereby prolong health and independence in later life.

PMID- 11982671
TI  - Cognitive impairment after stroke: clinical determinants and its associations
      with long-term stroke outcomes.
AB  - OBJECTIVES: To identify factors that were associated with cognitive impairment 3
      months after stroke, and to examine the associations of cognitive impairment with
      stroke outcomes up to 4 years after stroke. DESIGN: Observational study. SETTING:
      Population-based stroke register. PARTICIPANTS: Six hundred forty-five subjects
      with first-ever stroke, identified from the register. MEASUREMENTS: Subjects were
      assessed for cognition using the Mini-Mental State Examination (MMSE) 3 months
      after stroke. Cognitively impaired subjects (MMSE <24, n = 248 (38%)) were
      compared with cognitively intact subjects (MMSE 24-30, n = 397) in terms of
      demographic details, stroke risk factors, laterality of stroke, and initial
      poststroke impairments. Outcome data collected at 1, 3, and 4 years poststroke
      included disability assessed by the Barthel Index (BI) and the Frenchay Activity
      Index, case fatality, and institutionalization. RESULTS: Two hundred forty-eight
      (38%) of 645 subjects were cognitively impaired 3 months after stroke. Using
      multivariate analyses, cognitive impairment was associated with age of 75 and
      older (odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.5-4.2), ethnicity
      (Caribbean/African (OR = 1.9, 95% CI = 1.2-3.2) and Asian (OR = 3.4, 95% CI = 1.1
      10.2), lower socioeconomic class (OR = 2.1, 95% CI = 1.3-3.3), left hemispheric
      lesion (OR = 1.6, 95% CI = 1.01-2.4), visual field defect (OR = 2.0, 95% CI = 1.2
      3.2), and urinary incontinence (OR = 4.8, 95% CI = 3.1-7.3). Using multivariate
      analyses, cognitive impairment was associated with death or disability (BI <15)
      at 4 years after stroke (OR = 2.2, 95% CI = 1.1-4.5). In univariate analyses, it
      was also associated with higher institutionalization 4 years after stroke (P
      =.001). CONCLUSIONS: Cognitive impairment is common 3 months after stroke and is
      independently associated with older age, ethnicity, lower social class, left
      hemispheric stroke, visual field defect, and urinary incontinence. It is
      associated with poor long-term outcomes, including survival and disability, up to
      4 years after stroke. Because physical and cognitive impairments after stroke
      have independent prognostic implications, measures that evaluate both functions
      should be used in future studies of stroke outcome and in care of stroke
      patients.

PMID- 11982672
TI  - Sex hormones and cognitive function in older men.
AB  - OBJECTIVES: Recent studies have suggested that estrogen may improve cognitive
      function or prevent cognitive decline in older women. Little research has been
      conducted on exogenous or endogenous sex hormones and cognition in older men, yet
      it has been hypothesized that testosterone, either directly or by conversion to
      estrogens, may improve cognitive function. We investigated whether serum level of
      testosterone and estradiol is associated with cognition in older community
      dwelling men. DESIGN: A cross-sectional study. SETTING: Population-based listings
      in the Monongahela Valley near Pittsburgh, Pennsylvania. PARTICIPANTS: Three
      hundred ten men (mean age +/- standard deviation = 73.0 +/- 7.1) who were part of
      a cohort study. MEASUREMENTS: We measured cognitive function using the Mini
      Mental State Examination (MMSE), Trails B, and Digit Symbol. Sex hormone levels
      were determined by radioimmunoassay from serum obtained at the time of cognitive
      testing and analyzed by tertile. RESULTS: No consistent association between total
      testosterone level and cognitive test scores was observed. However, men with high
      bioavailable (loosely protein-bound) testosterone had better cognitive test
      scores on all three tests (P < or =.001). Total estradiol levels were associated
      with worse cognitive scores on Digit Symbol (P <.001) and Trails B (P =.002), but
      bioavailable estradiol levels were not associated with cognitive function. Level
      of sex hormone binding globulin (SHBG) was negatively associated with cognitive
      scores on all three tests (P < or =.001). After adjusting for age and education,
      the statistical significance lessened for bioavailable testosterone (MMSE, P
      =.086; Digit Symbol, P =.047; Trails B, P =.076) and became nonsignificant for
      SHBG (all cognitive tests P>.10). CONCLUSIONS: Our findings support the
      hypothesis that higher levels of bioavailable testosterone, but not of
      bioavailable estradiol, are associated with better cognitive function in older
      men. In addition, bioavailable measures of testosterone may better reflect
      hormone levels available to the brain and thus be more closely associated with
      central nervous system outcomes such as cognition. Future studies, especially
      randomized trials, should be undertaken to determine whether testosterone may
      protect against cognitive decline in older men.

PMID- 11982673
TI  - Differential effects of premorbid physical and emotional health on recovery from
      acute events.
AB  - OBJECTIVES: Emotional health may have an important effect on disease onset, but
      there has been little work evaluating premorbid emotional health on recovery from
      disability that results from acute medical events. The aim of this study is to
      determine whether premorbid emotional health is predictive of recovery in
      functional ability 1 year after reporting a stroke, heart attack, or hip fracture
      (event). DESIGN: A prospective cohort study of an older population-based sample
      from 1986 to 1992. SETTING: Data are from baseline and six annual follow-ups of
      the North Carolina Established Population for Epidemiological Study of the
      Elderly. PARTICIPANTS: Two hundred forty whites and blacks aged 65 and older who
      reported a stroke, heart attack, or hip fracture during one of the first five
      follow-up interviews and had an increased level of disability at that follow-up.
      MEASUREMENT: Improvement in disability in activities of daily living (ADLs) 1
      year postevent. RESULTS: High depressive symptoms at baseline showed a
      significant association with poorer recovery in functional ability 1-year
      postevent after adjustments were made for sociodemographic characteristics,
      smoking status, ADLs at time of event, cognitive status, and prior history of
      disease. Compared with nondepressed subjects, depressed subjects had an odds
      ratio (OR) of 0.38 (95% confidence interval (CI) = 0.16-0.94) for recovery 1 year
      after reporting a stroke, heart attack, or hip fracture. Additionally, among
      subjects who reported low depressive symptoms, high positive affect was
      significantly associated with increased odds of recovery (OR = 2.70, 95% CI =
      1.10-6.68), adjusting for the same variables. CONCLUSIONS: Emotional health,
      independent of other baseline measures, is associated with recovery in functional
      ability 1 year after a major health event. Our findings suggest that reducing
      premorbid levels of depressive symptoms or increasing positive affect may help
      the recovery process.

PMID- 11982674
TI  - Nursing home residents covered by Medicare risk contracts: early findings from
      the EverCare evaluation project.
AB  - OBJECTIVES: To compare the characteristics of a sample of EverCare nursing home
      residents with two control groups: one composed of other residents in the same
      homes and another made up of residents in matched nursing homes. To compare
      levels of unmet need, satisfaction with medical care, and the use of advance
      directives. DESIGN: Quasi-experimental design using two control groups to
      minimize selection effects. Information collected by in-person surveys of nursing
      home residents and telephone surveys of proxies and family members. SETTING:
      Nursing homes affiliated with EverCare and matched control homes. PARTICIPANTS:
      Nursing home residents and their family members. MEASUREMENTS: Questionnaire
      addressing function (activities of daily living (ADLs)), unmet care needs, pain,
      use of advance directives, satisfaction, and caregiver burden. RESULTS: In
      general, the experimental and control groups were similar, but the EverCare
      sample had more dementia and less ADL disability. Family members in the EverCare
      sample expressed greater satisfaction with several aspects of the medical care
      they received than did controls. Satisfaction of residents in the EverCare sample
      was more comparable with that of controls. There was no difference in experience
      with advance directives between EverCare and control groups. CONCLUSIONS:
      EverCare appears to be a model of managed care worth tracking. It is producing
      care that is at least comparable with what is available in the fee-for-service
      environment, with evidence that families seem to appreciate the added attention.
      There is some suggestion that it has enrolled a less disabled but more demented
      population. Pending results on the effects of this care on hospitalization and
      emergency care should shed useful light.

PMID- 11982675
TI  - Pressure ulcer prevalence in long-term nursing home residents since the
      implementation of OBRA '87. Omnibus Budget Reconciliation Act.
AB  - OBJECTIVES: To evaluate change in pressure ulcer prevalence in long-term nursing
      home residents since the implementation of the Omnibus Budget Reconciliation Act
      of 1987 (OBRA '87). DESIGN: Cross-sectional comparison of two time periods.
      SETTING: Ninety-two nursing homes scheduled for a quality-of-care survey randomly
      selected from 22 representative states. PARTICIPANTS: Four thousand six hundred
      seventy-nine residents who had resided in the facility for at least 100 days were
      evaluated: 2,336 during 1992-1994 and 2,343 during 1997-1998. MEASUREMENTS:
      Trained registered nurses collected data on pressure ulcer prevalence, stage, and
      risk factors from medical record review during on-site evaluations. Risk-adjusted
      differences were estimated using logistic regression. RESULTS: Unadjusted
      prevalence rates for all stages of pressure ulcers (8.52% vs 8.54%, P =.983) and
      those rated stage 2 or greater (5.31% vs 5.63%, P =.624) did not differ between
      the two time periods. After adjustment for urinary incontinence, immobility, poor
      nutrition, and history of previous pressure ulcers, the relative odds of having a
      pressure ulcer in 1992/4 versus 1997/8 was 1.06 (95% confidence interval (CI) =
      0.84-1.34) for all stages and 1.21 (95% CI = 0.92-1.60) for stages 2 and greater.
      CONCLUSIONS: No change in pressure ulcer prevalence was demonstrated since
      implementation of OBRA '87 in this nationally derived sample of long-term nursing
      home residents.

PMID- 11982676
TI  - Informal caregiving time and costs for urinary incontinence in older individuals
      in the United States.
AB  - OBJECTIVES: To obtain nationally representative estimates of the additional time,
      and related cost, of informal caregiving associated with urinary incontinence in
      older individuals. DESIGN: Multivariate regression models using data from the
      1993 Asset and Health Dynamics Study, a nationally representative survey of
      people aged 70 and older (N = 7,443). SETTING: Community-dwelling older people.
      PARTICIPANTS: National population-based sample of community-dwelling older
      people. MEASUREMENTS: Weekly hours of informal caregiving, and imputed cost of
      caregiver time, for community-dwelling older people who reported (1) no
      unintended urine loss, (2) incontinence that did not require the use of absorbent
      pads, and (3) incontinence that required the use of absorbent pads. RESULTS:
      Thirteen percent of men and 24% of women reported incontinence. After adjusting
      for sociodemographics, living situation, and comorbidities, continent men
      received 7.4 hours per week of care, incontinent men who did not use pads
      received 11.3 hours, and incontinent men who used pads received 16.6 hours (P
      <.001). Women in these groups received 5.9, 7.6, and 10.7 hours (P <.001),
      respectively. The additional yearly cost of informal care associated with
      incontinence was $1,700 and $4,000 for incontinent men who did not and did use
      pads, respectively, whereas, for women in these groups, the additional yearly
      cost was $700 and $2,000. Overall, this represents a national annual cost of more
      than $6 billion for incontinence-related informal care. CONCLUSIONS: The quantity
      of informal caregiving for older people with incontinence and its associated
      economic cost are substantial. Future analyses of the costs of incontinence, and
      the cost-effectiveness of interventions to prevent or treat incontinence, should
      consider the significant informal caregiving costs associated with this
      condition.

PMID- 11982677
TI  - Evening light exposure: implications for sleep and depression.
AB  - OBJECTIVES: To examine whether dim illumination in the evening is a factor in
      sleep disturbances of aging, depression, and circadian phase advance. DESIGN: One
      week continuous recordings were made to record illumination exposure and to infer
      24-hour sleep patterns from wrist activity. SETTING: Recordings took place during
      normal home and community activities. PARTICIPANTS: Complete data of 154
      postmenopausal women, mean age 66.7, were selected from a larger study of
      participants in the Women's Health Initiative. MEASUREMENTS: Illumination in lux
      was averaged for 4 hours before bedtime and over 24 hours. Mood was measured
      using a brief eight-item screen. RESULTS: Illumination in the 4 hours before
      bedtime was quite dim: median 24 lux. Nevertheless, evening light exposure was
      not significantly related to sleep amount (in bed or out of bed) sleep
      efficiency, sleep latency, wake within sleep, or mood. In contrast, the overall
      amount of light throughout the 24 hours was negatively correlated with sleep
      latency, wake within sleep, and depressed mood. CONCLUSIONS: Low evening lighting
      does not appear to be a crucial factor in sleep and mood disturbances of aging,
      but overall lighting may contribute to these disturbances.

PMID- 11982678
TI  - A prospective evaluation of the Charlson Comorbidity Index for use in long-term
      care patients.
AB  - OBJECTIVES: Because of the high prevalence of coexisting medical conditions in
      frail older adults, clinical investigators often need to adjust for comorbidity
      when assessing the effect of long-term care (LTC) on patient outcomes. This study
      examined the prognostic value of the Charlson Comorbidity Index (CCI) in
      predicting 3-year mortality and functional decline in the LTC setting and
      compared its prognostic value to that of two data-derived comorbidity indices.
      DESIGN: Longitudinal cohort study. SETTING: Eighty-eight residential care
      facilities from Quebec, Canada. PARTICIPANTS: Two hundred ninety-one dependent
      older adults aged 65 and older. MEASUREMENTS: Subjects' functional abilities were
      assessed at baseline and 3 years later with the revised version of the Functional
      Autonomy Measurement System(SMAF). Comorbidity data and the exact date of death
      for those who had died were collected retrospectively from the subjects' medical
      files. Subjects were classified as functional decliners if they died or gained 5
      points or more on the SMAF between the two assessments. RESULTS: Multivariate Cox
      and logistic regressions were used to derive two new comorbidity indices, one for
      predicting mortality and the other for identifying functional decliners. Although
      the CCI performed well in predicting these two outcomes, its performance was
      generally inferior to that of the two newly proposed indices. CONCLUSIONS:
      Findings suggest that the CCI can be improved upon when used to measure
      comorbidity in LTC patients.

PMID- 11982679
TI  - Evaluation of the effectiveness of Tai Chi for improving balance and preventing
      falls in the older population--a review.
AB  - One of the challenges faced by people with advancing age is decreased postural
      stability and increased risks for falls. There has been an increased interest
      over the last decade in using Tai Chi as an intervention exercise for improving
      postural balance and preventing falls in older people. Despite the increased
      number of studies in recent years relating Tai Chi to balance and fall
      prevention, results are scattered and inconsistent. There is wide variation in
      the use of balance measures, subject population, type and duration of Tai Chi
      exercise, and type of study. This paper provides a systematic review/analysis of
      currently available study reports. The goal of the review is to address the
      following concerns: how the effect of Tai Chi on balance or fall prevention has
      been evaluated to date, what level of evidence exists supporting Tai Chi as an
      effective exercise for improving balance or preventing falls, and what factors
      could possibly affect the benefit of Tai Chi on balance or falls. This review
      also helps identify directions for future research.

PMID- 11982680
TI  - Developing a geriatric business plan for an academic medical center.
AB  - Leaders of geriatric programs at academic health centers (AHCs) face several
      challenges in seeking support for clinical program development. These challenges
      relate to how revenues from Medicare activities flow within AHCs. Typically,
      clinical departments such as the Department of Medicine see a very small
      proportion of total AHC Medicare revenue and frequently experience losses on
      their Medicare activities. In contrast, hospitals in AHCs see the bulk of the
      revenues and typically experience substantial profits. This article examines this
      situation in some detail, with specific examples from AHCs with which the author
      has consulted.The unique effect of Medicare revenue on AHCs requires the
      geriatric leader to identify who gains and who loses from Medicare activity
      within his or her AHC and to seek support for geriatric programs based on that
      analysis.

PMID- 11982681
TI  - Advance care planning by proxy for residents of long-term care facilities who
      lack decision-making capacity.
AB  - This report examines whether long-term care facilities should implement policies
      and procedures to support advance care planning by proxy for residents who lack
      decision-making capacity. The report focuses on advance care planning in the
      Department of Veterans Affairs. After reviewing clinical, legal, and ethical
      perspectives, the authors conclude that advance proxy planning is ethically sound
      and can improve patient care. However, because experience with advance proxy
      planning is still fairly limited, the authors do not recommend that a particular
      standardized approach be mandated at the national level. Instead, local
      facilities are advised to develop their own policies and then evaluate their
      effect. The report contains specific recommendations for the advance proxy
      planning process.

PMID- 11982682
TI  - An incentive to start hormone replacement: the effect of postmenopausal hormone
      replacement therapy on the risk of colorectal cancer.

PMID- 11982683
TI  - Wheelchair users are not necessarily wheelchair bound.

PMID- 11982684
TI  - What do prevalence studies of pressure ulcers in nursing homes really tell us?

PMID- 11982685
TI  - Tolterodine: a safe and effective treatment for older patients with overactive
      bladder.

PMID- 11982686
TI  - Benzodiazepines and insomnia.

PMID- 11982687
TI  - Gene for medical cost?

PMID- 11982688
TI  - The long-term effect of estriol on endothelial function and bone mineral density
      in octogenarian women.

PMID- 11982689
TI  - Improvement of cognitive function after pacemaker implantation in very old
      persons with bradycardia.

PMID- 11982690
TI  - Iloprost for age-related macular degeneration: long-term efficacy evaluation.

PMID- 11982691
TI  - Thalidomide in inflammatory bowel disease: too little, too soon.

PMID- 11982692
TI  - Microscopic colitis.
AB  - Microscopic colitis is an umbrella term used to include two idiopathic
      inflammatory bowel disorders that present with chronic watery diarrhea, normal
      endoscopic findings and characteristic inflammatory changes on histology.
      Collagenous colitis and lymphocytic colitis are distinguished by the presence of
      a thickened subepithelial collagen table. It is likely that they are a spectrum
      of one disease, but this is yet to be proven. The majority of cases tend to
      undergo spontaneous remission within a few years of onset, and their clinical
      course is benign, with no increase in risk of colorectal cancer. Sufficient
      evidence exists to suggest that microscopic colitis occurs as a response to one
      or more luminal antigens. A variety of medications have been reported in the
      treatment of this condition, but only colloidal bismuth and budesonide have thus
      far been shown to be effective in randomized controlled trials.

PMID- 11982693
TI  - Physiological small bowel malabsorption of carbohydrates protects against large
      bowel diseases in Africans.
AB  - In African black people there is a paucity of 'developed society' large bowel
      diseases such as diverticular disease, colorectal adenomas and carcinomas,
      ulcerative colitis and Crohn's disease. Appendicitis has an incidence of about 5
      10% of the number likely to be observed in a white population. The conundrum is
      that the disparity exists despite many Africans having adopted an urbanized
      lifestyle with major changes in their dietary pattern. Dietary fiber intake,
      which was previously 30-35 g, has decreased to 12-14 g daily. Studies on small
      bowel function in black people have shown that physiological malabsorption of
      lactose, fructose, sucrose and maize (the staple food) occurs. It is hypothesized
      that the increased concentration of substrate available for fermentation in the
      colon compensates for the low dietary fiber intake, is protective to the large
      bowel and is a factor in the prevention of 'developed society' large bowel
      diseases in the African population.

PMID- 11982694
TI  - Helicobacter pylori infection promotes gastric carcinogenesis in a mice model.
AB  - BACKGROUND AND AIM: Debate that Helicobacter pylori might play a causative role
      in gastric carcinogenesis still exists in spite of the World Health
      Organization's definition of H. pylori as a class I carcinogen. In order to
      define the exact role of H. pylori infection in gastric carcinogenesis, we
      established a mice model of H. pylori infection. METHODS: One hundred and forty
      four female C57BL/6 mice were divided into nine groups according to N-methyl-N
      nitrosourea (MNU) treatment and H. pylori infection. All mice were killed at the
      50th or 80th week after treatment, and their histopathological changes were
      evaluated according to group. RESULTS: The incidence of gastric adenocarcinoma at
      the 50th week was 80% in mice treated with both MNU 240 microg/L and H. pylori
      infection, whereas the incidence was only 27% in mice treated with only MNU 240
      microg/L. Although H. pylori caused marked expansion of the proliferative zone at
      the surface epithelium, H. pylori infection alone caused only chronic atrophic
      gastritis without any evidence of carcinomas until 80 weeks. The combination of
      MNU and H. pylori infection also resulted in a significantly higher incidence of
      gastric adenoma and adenocarcinoma. Significantly higher expressions of
      proliferating cell nuclear antigen were noted in the gastric mucosa infected with
      H. pylori compared to controls. CONCLUSIONS: These results clearly demonstrated
      the role of H. pylori infection, rather than direct carcinogens, in promoting
      gastric carcinogenesis in a mice model.

PMID- 11982695
TI  - Cell kinetics of slow renewing cell populations in mice stomach.
AB  - BACKGROUND: The renewal rates of parietal and chief cells in the gastric mucosa
      and smooth muscle cells of muscularis propria have not been examined as precisely
      as superficial epithelial cells. To examine cell renewal of these cells,
      continuous labeling with tritiated ([3H])-thymidine was performed. METHODS: Mice
      received 112 repeated injections of [3H]-thymidine at 6-hour intervals for 28
      days after birth and were killed immediately thereafter, or 60, 120, 200 or 300
      days after the last injection. RESULTS: After continuous labeling, most cells in
      the stomach were labeled. At 60 days, unlabeled parietal cells in the neck area
      of the gland and unlabeled chief cells in the middle part of the gland appeared.
      Thereafter, the area of unlabeled cells expanded downwards to the bottom of the
      gland. Times required for labeling of total cell populations of parietal and
      chief cells to half were less than 60 days and more than 200 days, respectively.
      At 300 days, most parietal cells and about half of the chief cells remained
      labeled in the bottom of the gland. The labeling index of smooth muscle cells was
      about 100% for 300 days. CONCLUSIONS: The time required for the newly formed
      parietal and chief cells to reach the lower end of the gland was more than 300
      days. As a total cell population, the renewal rate of parietal cells was more
      rapid than that of chief cells. However, in terms of the downward migrating cell
      population, the renewal rate of parietal cells was a little slower than that of
      chief cells. Smooth muscle cells showed almost no renewal.

PMID- 11982696
TI  - Study of the motile activity of the colon in rectal inertia constipation.
AB  - BACKGROUND: We have recently demonstrated that rectal distension effected left
      colonic contraction, which probably acts to feed the rectum with fecal matter
      each time the rectum distends and evacuates its contents. This effect was
      postulated to occur through the recto-colic reflex. As the colonic status in
      rectal inertia constipation was scarcely addressed in the literature, we
      investigated this point. METHODS: The response of the colonic pressure to rectal
      balloon distension in increments of 10 mL of water was studied in 38 patients
      with rectal inertia constipation (IC) (age 42.6 +/- 14.3 years, 29 women) and 12
      healthy volunteers (40.9 +/- 12.2 years, nine women). The rectal and colonic
      pressures were measured by saline-perfused tubes connected to a pneumohydraulic
      infusion system. The rectum was distended by a condom applied to the end of a 10
      F catheter. RESULTS: The rectal and left colonic resting pressures were
      significantly lower in the patients than in the controls (P < 0.5, P < 0.05,
      respectively). In the healthy volunteers, rectal distension up to first rectal
      sensation produced no significant rectal or colonic pressure changes (P > 0.05, P
      > 0.05). At urge, rectal and left colonic pressures increased significantly (P <
      0.001, P < 0.001, respectively), but there were no changes in the right colonic
      pressure (P > 0.05). The colonic response lasted as long as the rectum was
      distended. In IC, patients did not perceive the first rectal or urge sensation up
      to a rectal balloon filling of 300 mL; there was no rectal or colonic pressure
      response (P > 0.05, P > 0.05). CONCLUSION: In normal subjects, left colonic
      contraction on rectal distension probably acts to feed the rectum with fecal
      material. In IC, the low left colonic resting pressure assumedly points to left
      colonic hypotonia which appears to aggravate the constipation produced by the
      inertic rectum. Furthermore, non-response of the left colon to rectal distension
      probably impedes rectal feeding with fecal matter and enhances constipation.

PMID- 11982697
TI  - Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in
      patients undergoing colonoscopy for diarrhea.
AB  - BACKGROUND AND AIMS: In patients undergoing colonoscopy for diarrhea, when the
      examination is normal, the role of routine mucosal biopsy remains controversial,
      particularly in the open-access setting. It is uncertain whether routine
      ileoscopy adds anything to colonoscopy alone. We aimed to assess the yield of
      mucosal biopsy and ileoscopy in patients with diarrhea. METHODS: We
      retrospectively reviewed all colonoscopies performed for diarrhea over a 9-year
      period in a tertiary referral center with an open-access service. We then
      selected cases where the examination was normal and biopsies were performed. The
      histopathology reports of these selected cases were then reviewed. RESULTS: There
      were 1131 cases identified. The mucosal examination was normal in 465 cases
      (41%); 362 of these had colonic biopsies performed. Histology was normal in 316
      cases (87%) and was non-specific in 28 cases (8%). Significant histopathology was
      present in 18 cases (5%) with a significantly higher prevalence of microscopic
      colitis in patients above 60 years old. Ileoscopy was performed in 508 cases and
      was abnormal in 26 cases (5%). The abnormality on ileoscopy was the sole
      abnormality in 13 cases (3%). CONCLUSIONS: Routine colonic mucosal biopsy and
      ileoscopy each identify significant additional pathology in 5% of cases when
      investigating patients with diarrhea, and are recommended as routine practice in
      this setting. We found ileal biopsy unhelpful when ileoscopy was normal.

PMID- 11982698
TI  - Predictive factors by multivariate analysis for colorectal cancer in Malaysian
      patients undergoing colonoscopy.
AB  - BACKGROUND: The majority of colorectal cancers are still diagnosed in patients
      who present with symptoms especially in countries where colorectal screening
      programs are not practised. The aim of our study was to determine the predictive
      factors for colorectal cancer in patients referred for colonoscopy. METHODS: A
      prospective study of 485 consecutive patients who underwent colonoscopy during a
      22-month period was performed. All patients answered a detailed questionnaire.
      Indications for colonoscopy and the findings were recorded. RESULTS: The mean age
      of the study population was 55.7 +/- 14.7 years. There were 221 (45.6%) males and
      264 (54.4%) females. Sixty-five (13.4%) were Malays, 298 (61.4%) were Chinese and
      112 (23.1%) were Indians. Multiple backward stepwise regression analysis revealed
      that independent predictors for colorectal cancer (odds ratio [95% CI]) were the
      presence of rectal bleeding (4.3 [4.0-8.0]) and iron deficiency anemia (4.0 [3.6
      10.2]). In those aged 50 and over, male gender (4.5 [2.2-9.3]) and abdominal pain
      (3.1 [1.4-6.7]) were also significant positive predictors of cancer. CONCLUSIONS:
      With the ever-increasing demand for gastrointestinal endoscopy, the appropriate
      utilization of colonoscopy is essential to afford prompt patient evaluation. Our
      study supports the need to prioritize the use of colonoscopy in patients with
      rectal bleeding and iron deficiency anemia. In the older patient where the
      background prevalence of colorectal cancer is higher, referral for colonoscopy is
      also justified.

PMID- 11982699
TI  - Serum gamma-interferon-inducing factor (IL-18) and IL-10 levels in patients with
      acute hepatitis and fulminant hepatic failure.
AB  - BACKGROUND AND AIMS: The aim was to determine the role of T-helper (Th)1/Th2
      cytokine responses in the clinical outcome of patients with acute liver injury.
      METHODS: The serum levels of the cytokines, interleukin (IL)-18, gamma-interferon
      (IFN-gamma), IL-10 and IL-4 were measured in 20 fulminant hepatic failure (FHF),
      18 acute hepatitis (AH), 30 chronic viral hepatitis and 20 liver cirrhosis (LC)
      patients. Thirteen cases were from the intensive care unit (ICU) and there were
      21 healthy volunteers. Immunohistochemical staining of liver biopsies for IL-18
      expression was also performed. RESULTS: Serum IL-18 levels in patients with FHF
      were significantly more elevated than in patients with other liver diseases, ICU
      cases and healthy volunteers. Furthermore, serum IFN-gamma levels in patients
      with FHF were also significantly higher than in patients with chronic viral
      hepatitis, LC and healthy volunteers. We found a positive correlation between the
      levels of IL-18 and IFN-gamma. However, no relationship was observed between
      these and clinical outcome. In immunohistochemical staining, CD68+ macrophage
      cells and IL-18-positive cells were observed in portal zones. Elevated serum IL
      10 levels were restricted to patients presenting with FHF, and were significantly
      higher in surviving cases (P < 0.01). Furthermore, serum IL-10 levels, but not IL
      4 levels, were inversely correlated with serum total bilirubin concentrations (P
      = 0.045) and the death rate (p) outlined in Japan (P = 0.030). CONCLUSION: These
      results suggest that IL-18 and IFN-gamma are involved in the pathogenesis of
      acute hepatic injury in humans, and that, in particular, elevated serum levels of
      IL-10 may be predictive of improved outcomes for these patients.

PMID- 11982700
TI  - A survey of Australian general practice management of hepatitis C-infected
      patients from non-English-speaking backgrounds.
AB  - BACKGROUND: Australia receives many migrants from countries with a high
      prevalence of hepatitis C infection. General practitioners, who are often the
      first health professionals consulted, need to be aware of risk factors and
      complications associated with hepatitis C in this group. METHODS: Four hundred
      and forty-seven general practitioners, obtained from registries at two Melbourne
      teaching hospitals serving large non-English-speaking migrant populations, were
      sent a questionnaire. Two hundred and forty-one returned a completed
      questionnaire. The survey attempted to assess knowledge of risk factors,
      complications, currently recommended antiviral therapy, referral practice to
      specialists and difficulties encountered by practitioners and patients in
      accessing information about HCV. RESULTS: Sexual and vertical transmission were
      listed as more common risk factors than iatrogenic causes or injecting drug use.
      Most respondents interpreted basic diagnostic tests correctly but there was a
      range of estimates regarding progression to cirrhosis and hepatocellular
      carcinoma with many seriously overestimating these aspects of natural history.
      Interferon and ribavirin were commonly listed as optimal therapy, but both
      interferon monotherapy and lamivudine, a treatment for hepatitis B, were stated
      as optimal therapy by 25% of respondents. Considerable frustration was expressed
      regarding access to reliable information about treatment outcomes and to
      linguistically and culturally appropriate patient information. CONCLUSIONS: The
      wide response range regarding modes of acquisition of HCV in patients from non
      English-speaking backgrounds, rates of progression to cirrhosis and
      hepatocellular carcinoma and optimal antiviral therapy suggests a need to improve
      provision of appropriate educational resources that will facilitate general
      practice management of a common and important public health problem.

PMID- 11982701
TI  - Reciprocal relationship between methylation status and loss of heterozygosity at
      the p14(ARF) locus in Australian and South African hepatocellular carcinomas.
AB  - Chromosome 9p21, a locus comprising the tumor suppressor genes (TSG) p16(INK4a)
      and p14(ARF), is a common region of loss of heterozygosity (LOH) in
      hepatocellular carcinoma (HCC). p14(ARF) shares exon 2 with p16 in a different
      reading frame. p14 binds to MDM2 resulting in a stabilization of functional p53.
      This study examined the roles of p14, p16 and p53 in hepatocarcinogenesis, in 37
      Australian and 24 South African patients. LOH at 9p21 and 17p13.1, p14 and p16
      mutation analysis, p14 and p16 promoter methylation and p14, p16 and p53 protein
      expression was examined. LOH at 9p21 was detected more frequently in South
      African HCC (P = 0.04). Comparable rates of p53 LOH were observed in Australian
      and South African HCC (10/22, 45%vs 13/22, 59%, respectively). Hypermethylation
      of the p14 promoter was more prevalent in Australian HCC than in South African
      HCC (17/37, 46%vs 7/24, 29%, respectively). In Australian HCC the prevalence of
      p14 methylation increased with age (P = 0.03). p16 promoter methylation was
      observed in 12/37 (32%) and 6/24 (25%) in Australian and South African HCC,
      respectively. Loss of p16 protein expression was detected in 14/36 Australian HCC
      whereas p53 protein expression was detected in 9/36. Significantly, a reciprocal
      relationship between 9p21 LOH and p14 promoter hypermethylation was observed (P <
      or = 0.05). No significant association between p14 and p53 was seen in this
      study. The reciprocal relationship identified indicates different pathways of
      tumorigenesis and likely reflects different etiologies of HCC in the two
      countries.

PMID- 11982702
TI  - Detection of serum nitrite and nitrate in primary biliary cirrhosis: possible
      role of nitric oxide in bile duct injury.
AB  - BACKGROUND: The role of nitric oxide synthase (NOS) in autoimmune disease is
      gaining increased attention because of the relationships between NOS activity and
      T-lymphocyte subpopulations and, in particular, the influence of NO on cytokine
      production by Th1 versus Th2 cells. In addition, there is evidence that both the
      liver and infiltrating hepatic T cells have inducible NOS-2 activity. METHODS: We
      studied serum levels of nitrite (NO2-) and nitrate (NO3-) in groups of patients
      with liver disease secondary to hepatitis B, hepatitis C, autoimmune hepatitis
      and primary biliary cirrhosis (PBC). Simultaneously, in a nested subpopulation,
      we studied the liver expression of NOS-2. RESULTS: Interestingly, there was a
      significant elevation both of nitrite and of nitrate in patients with PBC but not
      other liver diseases. Despite such increments, there was no correlation of the
      levels of nitrite and nitrate with sera levels of tumor necrosis factor-alpha,
      interferon-gamma, alanine aminotransferase, total bilirubin, alkaline
      phosphatase, gamma-glutamyl transpeptidase, platelet count, IgG, IgM,
      antimitochondrial antibodies or prothrombin time. These data were extended by
      demonstrating the expression of NOS-2 by immunohistochemistry in 13/14 patients
      with PBC, including in 9/14 patient hepatocyte populations and 4/14 bile duct
      cells. In contrast, NOS-2 expression was noted in hepatitis B and hepatitis C,
      but only found within mononuclear cells. CONCLUSION: Our data suggest that NO
      produced through NOS-2 may play a role in the pathogenesis of bile duct injury in
      some PBC patients.

PMID- 11982703
TI  - Automated enzymatic mitochondrial antibody assay for the diagnosis of primary
      biliary cirrhosis: applications of a routine diagnostic tool for the detection of
      antimitochondrial antibodies.
AB  - BACKGROUND AND AIMS: An automated enzymatic mitochondrial antibody assay (EMA)
      kit for the diagnosis of primary biliary cirrhosis (PBC) has become commercially
      available recently. The aim of this study was to assess the clinical utility of
      the enzyme inhibition assay using this EMA kit for the diagnosis of PBC. METHODS:
      We tested the immunoreactivity of sera from 54 histologically confirmed Japanese
      PBC patients to the 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by enzyme
      inhibition assay using commercially available TRACE (EMA) assay kit, and compared
      the results with those of indirect immunofluorescence, commercial enzyme-linked
      immunosorbent assay (ELISA) using MESACUP Mitochondria M2 kit, and immunoblotting
      on bovine heart mitochondria. RESULTS: Of the 54 sera, 43 (80%) were positive for
      antimitochondrial antibodies (AMA) by immunofluorescence, 39 (72%) for enzymatic
      inhibitory antibody to pyruvate dehydrogenase complex (PDC) by EMA, 33 (61%) for
      immunoglobulin G (IgG) class anti-PDC antibody by ELISA, and 53 (98%) for IgG,
      IgM, or IgA class antibodies against at least one of the 2-OADC enzymes by
      immunoblotting. Of these, 43 (80%) were positive for IgG, IgM, or IgA class
      antibodies against the E2 subunit of PDC (PDC-E2) by immunoblotting. Thirty-six
      of the 54 sera (67%) showed identical results in all of the four assays, and 40
      (74%) were all negative or positive by EMA, ELISA, and immunoblotting in PDC
      relevant reactivity. There was a significant correlation between the number of
      detected immunoglobulin classes of anti-PDC-E2 by immunoblotting and anti-PDC by
      EMA (P < 0.0001), and a significant inverse correlation between IgG class anti
      PDC by ELISA and units of PDC activity by EMA (r = -0.87, P < 0.0001).
      CONCLUSIONS: Although EMA had lower sensitivity compared with immunofluorescence
      and immunoblotting, this assay should be included among the routine diagnostic
      tools for the detection of AMA specific to PBC in clinical laboratories because
      of its high specificity, objective read-out, and rapid turnaround time.

PMID- 11982704
TI  - Endothelin-3 induces both human and opossum gallbladder contraction mediated
      mainly by endothelin-B receptor subtype in vitro.
AB  - BACKGROUND: Endothelins are produced by gallbladder epithelial cells, suggesting
      a role in the regulation of gallbladder function. AIMS: To characterize the
      effect of endothelin-3 (ET-3) on human and Australian possum gallbladder
      contractility and identify the receptor(s) involved. METHODS: Human and possum
      gallbladder muscle strips were exposed to cumulative concentrations of ET-3 (10
      pmol/L-100 nmol/L). Strips were pretreated with either tetrodotoxin (TTX) (1
      micro mol/L), the selective ET receptor antagonists BQ-123 (ET(A)), BQ-788
      (ET(B)), alone or together, or the mixed ET antagonist tezosentan (all 1 micro
      mol/L). Maximal changes in tone were measured and expressed as percentage of
      carbachol (100 micro mol/L)-induced tone. ANOVA was used for statistical
      analysis. RESULTS: Endothelin-3 induced a concentration-dependent increase in
      tone in both human and pos-sum strips (P < 0.05) and at 100 nmol/L represented
      44.2 +/- 4.5% and 40.3 +/- 4.6% of carbachol-induced tone, respectively. The
      effect on human strips was TTX insensitive, whereas the possum concentration
      response curve was shifted to the right. Individually, BQ-123 and BQ-788 shifted
      the human concentration-response curve to the right, but a greater inhibition by
      BQ-788 was achieved in the possum (P < 0.05). However, BQ-123 plus BQ-788 further
      reduced the ET-3 effect (P < 0.001) to a level comparable to that observed in the
      presence of tezosentan in both human and possum strips. CONCLUSION: Endothelin-3
      produces potent gallbladder contraction in vitro, acting mainly via ET(B)
      receptors and also interacting with ET(A)receptors. The receptors are located on
      the smooth muscle, but in possum gallbladder, neural receptors may also be
      involved. These findings suggest that ET-3 may regulate motility of possum and
      human gallbladder.

PMID- 11982705
TI  - Biliary guidewire facilitates bile duct biopsy and endoscopic drainage.
AB  - BACKGROUND: The introduction of a guidewire through bile duct strictures may
      facilitate transpapillary bile duct biopsy and subsequent biliary drainage.
      METHODS: Endoscopic bile duct biopsy was attempted in 61 patients with bile duct
      strictures. After the introduction of a guidewire into the bile duct, biopsy
      forceps were inserted via the papilla. Both devices were inserted through the
      working channel (3.2 mm in diameter) of a conventional duodenoscope. After the
      procedure, an endoscopic naso-biliary drainage catheter was advanced along the
      guidewire. The success rate of inserting the biopsy forceps, the sensitivity of
      the biopsy, and the success rate of endoscopic biliary drainage after the biopsy
      were analyzed prospectively. RESULTS: The final diagnosis was malignant
      strictures in 50 patients and benign strictures in 11. The success rate of
      inserting biopsy forceps without performing endoscopic papillary balloon dilation
      was 85%. The sensitivity of the biopsy for primary bile duct cancer (83%) was
      significantly higher (P < 0.05) than that of pancreatic cancer (47%). All
      patients had successful endoscopic biliary drainage after the procedure.
      CONCLUSION: A previously placed guidewire facilitates insertion of biopsy forceps
      and endoscopic biliary drainage. The histological diagnosis of cancer is more
      likely with bile duct cancer than with pancreatic cancer.

PMID- 11982706
TI  - Does a fatty meal improve hepatic clearance in patients after endoscopic
      sphincterotomy?
AB  - BACKGROUND: Delayed biliary emptying is a cause of recurrent bile duct stones in
      patients after endoscopic sphincterotomy (ES) for choledocholithiasis. This study
      aimed to evaluate the effect of fatty meal on hepatic clearance in patients after
      ES. METHODS: Sixty patients who had received ES and complete clearance of bile
      duct stones were enrolled. Delayed hepatic clearance (45 min clearance of
      radioisotope [E45'] < 57%) from quantitative cholescintigraphy (QC) and absence
      of sphincteric function confirmed by sphincter of Oddi manometry were found in
      each patient after normalization of liver function. Patients then received
      another QC 30 min after a fatty meal (two fried eggs and 250 mL full milk, fat 28
      g) within 2 months. RESULTS: Improvement of hepatic clearance in QC after fatty
      meal was found in 20 of 24 (83%) cholecystectomized patients and 27 of 36 (75%)
      patients with intact gallbladder. The E45' after fatty meal was significantly
      higher than that without fatty meal (56 +/- 12%vs 40 +/- 9% in cholecystectomized
      patients, P < 0.001; 52 +/- 16%vs 35 +/- 11% in patients with intact gallbladder,
      P < 0.001). All patients tolerated the fatty meal well during fatty meal QC.
      CONCLUSIONS: Fatty meal can improve hepatic clearance in both patients with
      intact gallbladder and after cholecystectomy, so routine restriction of fat after
      ES may be inappropriate. However, further studies are needed to evaluate the role
      of diet in the prevention of recurrent biliary complications.

PMID- 11982707
TI  - Gastrointestinal: Cameron's erosions.

PMID- 11982708
TI  - Hepatobiliary and pancreatic: cholecystoenteric fistulae.

PMID- 11982709
TI  - Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated
      with lamivudine.
AB  - Fibrosing cholestatic hepatitis (FCH) is a rare and extremely severe form of
      hepatitis B virus (HBV) infection. This condition was originally described in HBV
      infected recipients after a liver transplantation. Recently, FCH has been
      reported not only in liver transplant recipients, but also in other
      immunosuppressed patients. It is characterized clinically by cholestatic hepatic
      dysfunction, and pathologically by severe periportal fibrosis, cholestasis,
      widespread balloon degeneration of hepatocytes, and only a mild infiltration of
      inflammatory cells. Without treatment, FCH is universally fatal within a few
      months of diagnosis. There have been only two isolated case reports of FCH with
      long-term patient survival, and one case report with treatment failure after
      lamivudine therapy. Because of the rarity of this clinical entity, the
      therapeutic efficacy of lamivudine in patients with FCH cannot be evaluated
      systematically. Here, we present four patients with HBV-related FCH treated with
      lamivudine. One received antineoplastic therapy for acute lymphoblastic leukemia,
      and the other three were renal graft recipients. Two patients who developed FCH
      after a renal transplantation survived with an improvement in liver function and
      were followed up for 20 and 30 months, respectively, and were found to be in good
      health. However, the other two patients died of sepsis, possibly as a consequence
      of the immunosuppression with hepatic failure despite lamivudine treatment. Our
      experience suggests that lamivudine can alter the grave natural history of FCH.

PMID- 11982711
TI  - Proceedings of the First Asia-Pacific Digestive Week, Sydney, September 2001.

PMID- 11982712
TI  - Management of bleeding in the cirrhotic patient.
AB  - Important advances have been made in the management of variceal bleeding. Despite
      these advances, bleeding in the patient with cirrhosis remains one of the most
      demanding clinical challenges that a gastroenterologist or gastrointestinal
      surgeon may face. The aim is to identify the source of bleeding, control active
      bleeding and prevent rebleeding. This requires a multidisciplinary team, and the
      optimal management algorithm depends on the clinical circumstance of the patient
      and the local availability of endoscopic, radiological and surgical expertise.
      Injection sclerotherapy is effective in stopping acute variceal bleeding, but has
      the drawback of a high incidence of complications. Endoscopic variceal ligation
      is just as effective, and is associated with fewer complications. An overtube
      allows repeated introductions of the endoscope to be more tolerable for the
      patient and protects the airway against aspiration of blood; its use should be
      encouraged in patients with massive bleeding. Newer ligators can deliver multiple
      bands without removal of the scope but the high cost of these disposable devices
      limits their widespread use. Bleeding from gastric varices is even more
      challenging; the treatment of choice is injection with cyanoacrylate glue. To
      prevent rebleeding, beta-blockers are recommended for all patients with large
      varices (including those which have never bled). Injection sclerotherapy or band
      ligation, conducted at weekly intervals after the initial control of bleeding, is
      equally effective at obliterating varices and decreasing the risk of further
      hemorrhage; band ligation results in fewer complications. Other newer treatment
      modalities for variceal bleeding, such as somatostatin analogs, transjugular
      intrahepatic portasystemic shunt and liver transplantation, offer more optimal
      approaches to control bleeding and prevent rebleeding, but may be prohibitively
      expensive. Even for the most affluent communities, affordability, cost
      effectiveness, and resource rationing are important considerations in management
      of patients with cirrhosis complicated by gastrointestinal bleeding.

PMID- 11982713
TI  - Safety of technology: infection control standards in endoscopy.
AB  - Transmission of infection related to gastrointestinal endoscopy continues to be a
      subject of much discussion. The principles of infection control during endoscopy
      are reviewed. Guidelines set forth by a number of gastrointestinal endoscopy
      associations have emphasized the need for meticulous cleaning of endoscopes
      immediately after use, followed by appropriate disinfection, rinsing and drying.
      Most, if not all, episodes of transmission of infection during endoscopy are
      associated with lapses in cleaning and disinfection protocols. The need for
      universal compliance with infection control standards, and for the development of
      strategies to achieve such compliance, is highlighted.

PMID- 11982714
TI  - Changing role of endoscopy in the new millennium. Bushell Lecture, Asia-Pacific
      Digestive Week 2001.
AB  - Endoscopy has confronted many challenges, including serology tests for
      Helicobacter pylori, virtual colonoscopy and magnetic resonance
      cholangiopancreatography. These new modalities might eventually replace endoscopy
      in diagnosing digestive tract diseases. New advancements such as capsule
      endoscopy, infrared spectroscopy, optical coherent tomography, and various
      therapeutic procedures have opened new horizons in the field. Endoscopists should
      keep their mind open and be prepared for the changing role of endoscopy in the
      new millennium.

PMID- 11982715
TI  - Changing disease burden and management issues for esophageal cancer in the Asia
      Pacific region.
AB  - The changing epidemiology of esophageal cancer in developed countries is from
      squamous cell type to adenocarcinomas arising from Barrett's epithelium and the
      gastric cardia. This has implications for management of this disease. Earlier
      diagnosis of cancer from screening high-risk patients with Barrett's esophagus is
      potentially possible, and mucosal ablation together with acid-suppressive
      therapies have been investigated to revert Barrett's epithelium in its
      premalignant stage. When a cancer has developed, the strategies of staging
      methodology and surgical approaches also differ from those applicable for
      squamous cell cancers located in more proximal locations of the esophagus. By
      contrast, in the Asia-Pacific region (with the exceptions of Australia and New
      Zealand), squamous cell cancers in the middle portion of the esophagus remain the
      main cell type seen. An overall increase in life expectancy has led to more
      elderly patients presenting with carcinoma of the esophagus. This is of
      particular importance when surgical resection is contemplated. Advances in
      surgical management, multimodality programs, and endoscopic therapies are most
      marked in recent years. Treatment for patients with esophageal cancer should be
      individualized. The choice depends on expertise and facilities available, tumor
      and patient factors, and local economics.

PMID- 11982716
TI  - Endoscopic mucosal resection for esophageal and gastric cancers.
AB  - Better outcomes for digestive tract cancers are likely to be possible if the
      tumors are detected in their earliest stages, particularly when they exist as
      mucosal lesions without lymph node metastases. Early esophageal squamous cell
      cancers can be detected with high sensitivity and specificity by iodine staining.
      Only mucosal cancers are suitable for the curative approach of submucosal
      resection; the rate of metastasis is 4%, compared to a rate of metastasis of 35%
      in tumors with submucosal spread. In this review, the history of endscopic
      mucosal resection is reviewed, including the factors that have refined the
      technique and technical aspects crucial for effective results. The importance of
      adequate submucosal injection of dilute epinephrine in saline solution is
      particularly emphasized. The overall efficacy, low rate of complications and such
      practical aspects as post-therapeutic care are discussed. In general, mucosal
      cancers of the gastrointestinal tract have no risk of lymph node metastases and
      can be curatively managed by refined endoscopic mucosal resection procedures.

PMID- 11982717
TI  - When is molecular genetic testing for colorectal cancer indicated?
AB  - The genetic mutations causing many of the syndromes which confer a high inherited
      risk of colorectal cancer have now been identified. These include familial
      adenomatous polyposis, hereditary non-polyposis colorectal cancer, Peutz-Jeghers
      syndrome, Cowden's syndrome and juvenile polyposis. In all these diseases, the
      precise mutation is nearly always unique to a particular family; there are few
      mutation hot spots. This means that mutation detection is technically demanding.
      Nonetheless, genetic testing can now be used clinically to confirm the diagnosis
      in affected individuals, and to predict whether an "at risk" family member has
      inherited the disease and should therefore have endoscopic screening. Because
      current technology does not detect all mutations, a negative result in a
      definitely affected individual is diagnostically unhelpful and does not allow
      predictive testing of other family members. When a mutation can be detected, it
      is diagnostically very useful, and allows better management of all family
      members.

PMID- 11982718
TI  - Role of hepatitis C virus in the development of hepatocellular carcinoma:
      transgenic approach to viral hepatocarcinogenesis.
AB  - Overwhelming lines of epidemiologic evidence have indicated that chronic
      infection with hepatitis C virus (HCV) poses a major risk towards the development
      of hepatocellular carcinoma (HCC). It remains controversial whether HCV plays a
      direct role in the pathogenesis of HCV-associated HCC or whether it merely serves
      an indirect role. Using the transgenic mouse model established by us, it has
      become evident that the core protein of HCV confers oncogenic potential. The
      findings in our studies indicate that HCV is directly involved in
      hepatocarcinogenesis, albeit other factors, such as continued cell death and
      regeneration associated with chronic hepatitis, may also play a role. Taken
      together, our results indicate that there could be a mechanism for the
      development of HCC in persistent hepatitis virus infection that is distinct from
      the pathogenesis of other cancers, like colorectal cancer. Thus, although
      accumulation of a set of genetic aberrations may also be necessary for a
      multistage development of HCC, HCV core protein, to which an oncogenic potential
      is ascribed, may allow some stages to be skipped in hepatocarcinogenesis. The
      possibility that infection with HCV may be capable of inducing HCC in the absence
      of a complete set of genetic aberrations would help explain the unusually high
      incidence and multicentric nature of HCC developing in chronic hepatitis C.

PMID- 11982719
TI  - Natural history of hepatocellular carcinoma including fibrolamellar and hepato
      cholangiocarcinoma variants.
AB  - The natural history of hepatocellular carcinoma (HCC) varies greatly with the
      global region, because the carcinogenic factors are not the same among countries.
      Besides the clinicopathological factors such as tumor characteristics, sex, and
      age, background liver disease is a major determinant of prognosis. Hepatocellular
      carcinoma, mainly associated with chemical carcinogens such as aflatoxin, does
      not have severe background cirrhosis, and grows quickly, whereas HCC developing
      in association with a virus in a cirrhotic liver generally grows more slowly, and
      the severity of cirrhosis is the major prognostic factor. The median survival of
      untreated sub-Saharan African patients is less than 1 month from diagnosis,
      contrasted by an average survival of 4 months in virus-induced HCC associated
      with cirrhosis. Tumor characteristics, such as size, number, and growth speed,
      which vary considerably from case to case, affect the prognosis. Vascular
      (portal) invasion portends a poor prognosis, and alpha-fetoprotein levels also
      correlate with prognosis. Several distinct clinical types of HCC occur, namely
      diffuse-type HCC caused by rapid portal spread of cancer cells, febrile-type
      caused by poorly differentiated sarcomatoid cancer cells, and cholestatic HCC
      caused by intraductal invasion; all have a short survival. There are several
      histological variant forms: combined hepato-cholangiocarcinoma behaves like HCC,
      with a poorer prognosis because of more frequent lymph node metastases;
      fibromellar carcinoma, which is relatively common in young Caucasian adults, has
      a good prognosis if diagnosed early, permitting resection; and
      cholangiolocellular carcinoma, which derives from the canalicular epithelium, is
      indistinguishable from HCC, with a similar prognosis.

PMID- 11982720
TI  - Management of patients with chronic hepatitis B.
AB  - Better understanding of hepatitis B virus (HBV) replication and the natural
      history and immunopathogenesis of chronic hepatitis B, together with the
      introduction of effective agents with different mechanisms of action, is the
      basis for better therapeutic strategies against chronic hepatitis B. Substantial
      experience has now been accumulated in the use of some of these drugs, and an
      Asia-Pacific Consensus has been reached on indications for their use. The goals
      of therapy and aspects of general management will be reviewed here. Among
      currently available drugs, alpha-interferon therapy gives a response rate
      (hepatitis B e antigen (HBeAg) seroconversion) of 30-40% compared with 10-20% in
      matched controls, but patients with lower alanine aminotransferase (ALT), higher
      HBV-DNA, and immunosuppressed patients have a poorer response, and alpha
      interferon can be dangerous in cirrhosis. Meta-analysis of four controlled trials
      also suggests that thymosin-alpha1 is effective, but more studies are needed.
      Lamivudine has been most extensively studied. It is effective in terms of HBV-DNA
      loss, ALT normalization, HBeAg seroconversion, and improvement in histology, as
      well as being well tolerated. After 1 year of treatment, HBeAg seroconversion
      rate increased with higher pretherapy ALT levels, suggesting that patients with
      stronger endogenous antiviral defenses to kill hepatocytes harboring covalently
      closed circular DNA have a better response to direct antiviral effects.
      Lamivudine is also beneficial in HBeAg negative chronic hepatitis B, and patients
      with decompensated cirrhosis and HBV replication. However, genotypic-resistant
      tyrosine-methionine-aspartate-aspartate (YMDD) mutations start to emerge after 9
      10 months of lamivudine therapy, and their incidence increases more quickly than
      the HBeAg seroconversion rate durating prolonged therapy. Thus the benefits of
      long-term lamivudine must be balanced against concern about YMDD mutations, and
      the durability of treatment response. There are encouraging preliminary results
      for adefovir dipivoxil, entecavir, emtricitabine, clevudine and other
      nucleoside/nucleotide analogs in the early stages of appraisal; entecavir and
      adefovir dipivoxil appear effective in patients with YMDD mutants. Further
      development of new drugs and new strategies, such as combination or sequential
      therapy, may help to better achieve the goals of treatment for chronic hepatitis
      B in the new century.

PMID- 11982721
TI  - Treatment of chronic hepatitis B: case selection and duration of therapy.
AB  - Hepatitis B viral (HBV) infection is a major health burden in the Asia-Pacific
      region. The seriousness of chronic hepatitis B (CHB) is often realized at a late
      stage. The resultant morbidity and mortality from cirrhosis complications is
      considerable, with a high human cost. The most affected patients are men aged 40
      years or older. Two decades ago, the prognosis for the 300 million "Australia
      antigen"-positive people (people with chronic HBV infection) was gloomy, with no
      effective intervention. Twenty years on, research and development have changed
      their outlook. Chronic hepatitis should now be diagnosed early, at the
      asymptomatic stage. Proper assessment and judicial introduction of therapy can
      suppress replication of HBV and resolve liver inflammation, thereby preventing
      the silent progression of chronic liver disease to end-stage cirrhosis.
      Interferon (IFN) monotherapy has been available for nearly 20 years, but various
      limitations restrict its general application. Injection-based therapies are
      inconvenient, the response rate is low (33% hepatitis B e antigen (HBeAg)
      seroconversion rate among optimal cases), side-effects are many, and some
      serious, and the cost is unaffordable for most people. However, in non-cirrhotic
      patients with mild to moderate disease activity, IFN is still a worthwhile option
      because the treatment course is shorter, mutation seems less of a problem and
      most responses are permanent and reduce or abolish late complications.
      Lamivudine, an oral nucleoside analog with potent antiviral effects, has been
      approved in many countries. Daily dosing of 100 mg reduces serum HBV-DNA to below
      detectable levels within 6 weeks. In HBeAg-positive patients, approximately 16%
      of treated patients seroconverted with the first year. This was associated with
      significant improvement in liver histology. Long-term treatment induces further
      HBeAg seroconversion, but overall clinical benefit is undermined by continuous
      emergence of drug-resistant YMDD mutants. In an Asian multicentre study, 58
      patients on 5 years lamivudine therapy showed annual cumulative HBeAg
      seroconversion rates at 1, 2, 3, 4 and 5 years of 22, 29, 40, 47 and 50%,
      respectively. The best predictor of response is pretreatment alanine
      aminotransferase (ALT). Among patients with ALT > 2x the upper limit of normal
      (ULN), annual HBeAg seroconversion is increased to 38, 42, 65, 73 and 77%,
      respectively. However, emergence of YMDD mutants occurred at a cumulative rate of
      15, 38, 55, 67 and 69%, respectively. The impact of this emergence on disease
      activity is unpredictable. Thus, while continued disease suppression, or even
      HBeAg seroconversion, still occurred in some patients, in others hepatitis may
      relapse and liver failure has been reported despite continuation of lamivudine.
      While the duration of lamivudine therapy is difficult to define, the best
      strategy may be to define only active CHB with major ALT elevation (par-ticularly
      ALT > 5x ULN) for a duration of 1 year or less. Lamivudine can be stopped in
      responders. The response is durable in approximately 80% of responders. Non
      responders should be monitored closely for rebound off treatment. Therapy can be
      re-instituted if ALT is over 5x ULN. Management of patients with YMDD mutants can
      be challenging, but there is no clear evidence to recommend stopping or
      continuing lamivudine, or to add other possible effective agents, such as
      adefovir dipivoxil. More data are required to help draw up guidelines. Hepatitis
      B e antigen-negative CHB has been less well studied. Both IFN and lamivudine can
      suppress disease activity, but permanent responses are few. Without a distinct
      marker as an end-point for response, the duration of treatment is even more
      difficult to define. Quantitative polymerase chain reaction for low viral levels
      may give a clue, but definitive studies are required. Monotherapy is clearly not
      the answer for the majority of CHB patients with active disease. Combination
      therapy has the theoretical advantage of additional or synergistic efficacy.
      Preliminary results on IFN and lamivudine are promising and further clinical
      trials are ongoing. Emtricitabine (FTC), adefovir dipivoxil, entecavir, BL
      thymidine (L-dT), DAPD, clevudine (l-FMAU), thymosin, therapeutic vaccines and
      various herbal medicines are potential candidates. Antiviral action in
      conjunction with immune modulation may have a better chance of eradicating HBV
      and its cccDNA in the hepatocytes as the basis for an eventual successful
      outcome. The key points are: (i) approved therapeutic agents for chronic
      hepatitis B (CHB) are IFN, lamivudine and thymosin (in a few countries only);
      (ii) indications for IFN therapy are viremia in compensated CHB patients with
      moderately raised ALT; (iii) lamivudine has broader therapeutic indications: it
      is effective in subgroups of CHB patients with compensated or decompensated liver
      diseases, but generally works better if patients have raised ALT; (iv) lamivudine
      has a potent suppressive action on HBV replication, including HBeAg-negative
      variants, but cannot eliminate cccDNA; this is the reason for the relapse of
      disease after discontinuing treatment, unless HBeAg seroconversion is obtained;
      (v) successful use of lamivudine aims at HBeAg seroconversion or profound
      suppression of HBV-DNA to serum levels of less than 100 000 viral copies/mL, in
      order to prevent emergence of drug-resistant YMDD mutants (which commences from 6
      months onward); (vi) YMDD mutants may cause a flare of hepatitis, resulting in
      deterioration of liver histology and, occasionally, liver failure; (vii)
      combination therapy of lamivudine with IFN (standard or pegylated) or other
      nucleoside analogs should be the next advance. Preliminary data from IFN and
      lamivudine combination therapy show some promise, but there are conflicting
      results.

PMID- 11982722
TI  - Management issues in chronic viral hepatitis: hepatitis C.
AB  - The natural history of chronic hepatitis C virus (HCV) infection and intervention
      with antiviral therapy are closely linked issues that cause the greatest
      controversy and concern for the person infected with HCV, as well as for the
      clinician involved in the assessment and treatment of people with chronic HCV
      infection. The outstanding challenge of natural history is to identify the person
      who is likely to develop serious liver disease, and to make that determination
      early in the course of chronic HCV infection when treatment is likely to be of
      the greatest benefit. Significant advances in the therapy of chronic HCV
      infection have occurred over the past decade. A sustained virological response
      (SVR), defined as undetectable HCV-RNA in blood 6 months after completing
      antiviral treatment, is the best indicator of a beneficial treatment effect.
      Relapse, breakthrough or non-response should all be regarded as unsuccessful
      outcomes of therapy. Interferons are still the mainstay of antiviral therapy for
      chronic HCV infection. The combination of interferon and ribavirin has improved
      SVR by decreasing the relapse rate. Treatment responses vary according to host
      factors such as age and gender, fibrotic severity and to viral factors like
      genotype and viral load. Patients with genotype 1 HCV and a high viral load
      require 12 months of treatment to achieve a SVR in approximately 30%, compared to
      those with genotypes 2 or 3 who achieve a SVR in approximately 65% after 6
      months. Patients who relapse after an end-of-treatment response to interferon
      monotherapy have a good chance of responding to combination interferon and
      ribavirin given for 6 months, but a longer treatment course should be considered
      in less optimal cases. At present, the treatment of those with non-response is
      less clear, but there is interest in more intense forms of interferon therapy,
      such as induction dosing or pegylated interferon in combination with ribavirin.
      Clinicians need to be aware of the common side-effects of interferon and
      ribavirin so that appropriate counseling and testing can be instituted before and
      during therapy. The combination of pegylated interferon and ribavirin will be the
      new standard of therapy for hepatitis C and pegylated interferon monotherapy
      provides quite acceptable efficacy for those patients intolerant of ribavirin.
      Current data strongly support the concept that SVR in HCV infection (or treatment
      induced latency) provides a cure in terms of its beneficial effects on quality of
      life and sustained amelioration of liver injury.

PMID- 11982723
TI  - Is severe liver disease a common outcome for people with chronic hepatitis C?
AB  - For people with chronic hepatitis C, an assessment of their risk of progression
      to advanced liver disease is a major priority. Early studies of the natural
      history of chronic hepatitis C suggested that development of cirrhosis was a
      relatively common outcome, even in the first 20 years of infection. These studies
      were either cross-sectional liver clinic series of people referred for assessment
      to specialist clinics, or longitudinal cohorts of people with post-transfusion
      hepatitis. More recent studies (particularly longitudinal community-based
      cohorts) indicate that liver disease progression is generally slow, and that a
      minority of people with chronic hepatitis C will develop advanced liver disease.
      Based on an extensive review of studies reporting on chronic hepatitis C natural
      history, we have developed a Markov model of liver disease progression. This
      model estimates that the risk of progression to cirrhosis is 7% and 20% after 20
      and 40 years of infection, respectively. Corresponding estimates for hepatitis C
      related mortality are 1% and 4%. However, liver disease progression is highly
      variable, and certain subgroups of people with chronic hepatitis C are at
      increased risk of advanced liver disease. Those groups include people with a
      heavy alcohol intake, those who have coinfection with HIV or HBV, and those who
      have already progressed to moderate to severe hepatic fibrosis.

PMID- 11982724
TI  - Hepatitis C advances in antiviral therapy: what is accepted treatment now?
AB  - The vast number of patients with hepatitis C represent a huge medical and
      economic burden. While 20-30% of these patients progress and develop advanced
      liver disease, the majority do not. Thus, it is crucial to identify patients
      suitable for treatment and those who may benefit most from therapy. Anti-viral
      therapy is recommended for those patients with chronic hepatitis C who also have
      elevated liver tests, detectable hepatitis C virus ribonucleic acid and
      significant inflammation and/or fibrosis on liver biopsy. Currently, the most
      effective initial therapy is the combination of interferon plus ribavirin. The
      sustained viral response rate (SVR) is 36-41% following a 24- or 48-week course
      of therapy. In general, patients with the genotype 1 infection should receive 48
      weeks of therapy, and those with genotypes 2 or 3 infection only 24 weeks. Viral
      load estimations are problematic because of normal fluctuations (up to 0.5-10
      log), assay variability and lack of a universally accepted standard; thus, viral
      load testing is not recommended routinely at present. The sustained viral
      response rate produces improvements in quality of life and liver histology
      (including reversal of bridging fibrosis and cirrhosis is some), and durable
      responses lasting 5-11 years in 95-97% of cases. While the optimal dose of
      ribavirin is currently unknown, available data suggest that higher doses increase
      efficacy (albeit with a greater degree of anemia). The dose of 800 mg/day may be
      the most appropriate lower dose for those patients who require dosage
      modification for anemia or other side-effects. Patients who have relapsed after
      interferon monotherapy can be successfully retreated with higher doses of
      interferon for 1 year or the combination of interferon and ribavarin for 24-48
      weeks. Preliminary data suggest that patients with an unfavorable profile,
      including those with genotype 1 infection, should probably be retreated with
      interferon and ribavirin for 48 rather than 24 weeks. With our current best
      therapies, the majority of patients still do not achieve the benefits of a
      sustained response. Re-treatment with interferon and ribavirin may achieve a
      sustained response in approximately 10-25% of these patients. In the immediate
      future, once-weekly pegylated interferons will replace standard interferons.
      Initial data suggest that SVR achieved with these drugs in combination with
      ribavirin is increased to 54-61%, but dose modifications and side-effects are
      more frequent. They will thus provide an incremental benefit in terms of
      efficacy, particularly for genotype 1-infected patients.

PMID- 11982725
TI  - Advances in hepatitis C: what is coming in the next 5 years?
AB  - Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis
      and hepatocellular carcinoma. Numerous advances have been made in the
      understanding of HCV replication, including detailed molecular characterization
      of its viral proteins and genomic RNA. The inability to grow HCV in cell culture
      had impeded the development of antiviral agents against this virus. To overcome
      this obstacle, a number of unique tools have been prepared, such as molecular
      clones that are infectious in the chimpanzee animal model of infection, and the
      development of a subgenomic replicon system in Huh7 cells. In addition, the major
      non-structural proteins have been crystallized, thus enabling rational drug
      design directed to these targets. Current developments in antiviral agents are
      reviewed in the context of these potential new viral targets for the future
      treatment of HCV in chronically infected individuals.

PMID- 11982726
TI  - Treatment of alcoholic hepatitis.
AB  - Alcoholic hepatitis is a common disease with an overall 1-year mortality of 20%.
      Although the classical treatment for alcoholic hepatitis is abstinence, in some
      individuals abstinence alone is inadequate to promote survival and recovery. This
      is particularly true of patients with severe alcoholic hepatitis, who are
      identified by jaundice, coagulopathy and neutrophilia. Within the last two
      decades, several agents have been examined as treatments for alcoholic hepatitis
      and cirrhosis. They have targeted several key processes in the pathophysiology of
      alcoholic liver disease, including hypermetabolism, inflammation, cytokine
      dysregulation and oxidant stress. The compounds that offer the greatest survival
      benefit to patients with severe alcoholic hepatitis are corticosteroids. Several
      groups have reported excellent results with corticosteroids, but positive results
      are not uniform, and there remains some controversy over their efficacy. Even if
      corticosteroids are beneficial for alcoholic hepatitis, they are not recommended
      for all patients at risk. Consequently, other agents are being tested that have
      broader applicability to individuals with contraindications to steroids. In this
      regard, pentoxifylline shows some promise, as does enteral feeding with medium
      chain triglycerides. Independent efforts are also being directed toward treatment
      of chronic alcoholic liver disease and alcoholic cirrhosis. Anti-oxidants have
      received the greatest attention; drugs such as S-adenosyl-methionine may be of
      benefit. This and others are under active study.

PMID- 11982727
TI  - Management of refractory ascites and hepatorenal syndrome.
AB  - Refractory ascites and hepatorenal syndrome (HRS) are the late complications of
      the terminal stages of cirrhosis. The definitions of refractory ascites and HRS
      proposed by the International Ascites Club in 1996 are now widely accepted, and
      are useful in diagnosis, treatment and research in this field. In both
      conditions, the only treatment of proven value for improved survival is liver
      transplantation. However, because of better understanding about the
      pathophysiology of HRS, including the roles of portal hypertension, ascites
      formation and hemodynamic derangements, treatments such as transjugular
      intrahepatic portasystemic shunt (TIPS) and new pharmacological agents may be
      considered to alleviate the problem prior to transplantation. Symptomatic
      treatment of refractory ascites includes TIPS and repeated large volume
      paracentesis. Transjugular intrahepatic portasystemic shunt can improve survival
      while waiting for liver transplantation. Practical management guidelines for TIPS
      and large volume paracentesis, including the prevention and management of further
      complications, are considered in this review.

PMID- 11982728
TI  - Issues of malnutrition and bone disease in patients with cirrhosis.
AB  - Malnutrition is a frequent complication of cirrhosis, and many studies have
      demonstrated the adverse influence of malnutrition on clinical outcomes in
      patients with cirrhosis. The coexisting complications of fluid overload and
      ascites may mask the severity of malnutrition, particularly in the early stages
      of its development. During periods of decompensation, protein and energy
      requirements are higher, and many patients have inadequate nutritional intake at
      these times. Further, protein supplementation should not be restricted ad hoc in
      cirrhotic patients, as for the vast majority of patients dietary protein does not
      precipitate hepatic encephalopathy. The impairment of hepatic glycogen storage in
      cirrhotic patients effects a state of accelerated starvation with catabolism of
      fat and protein to provide substrates for gluconeogenesis. Recent studies have
      demonstrated the efficacy of nocturnal nutritional supplements in improving
      nitrogen balance. Resistance to the actions of the anabolic growth factors
      insulin and growth hormone (GH) is common in cirrhosis, and recent studies have
      shown that GH resistance, in particular, may be overcome with exogenous GH
      therapy. Hypermetabolism may be observed in up to one-third of cirrhotic
      patients. The recent exciting observation that beta-blocker therapy can decrease
      energy expenditure and catecholamine levels in these patients indicates the need
      for further intervention studies of beta-blockers as metabolic therapy in
      cirrhosis.

PMID- 11982729
TI  - Escherichia coli as a cause of diarrhea.
AB  - Escherichia coli is the best-known member of the normal microbiota of the human
      intestine and a versatile gastrointestinal pathogen. The varieties of E. coli
      that cause diarrhea are classified into named pathotypes, including
      enterotoxigenic, enteroinvasive, enteropathogenic and enterohemorrhagic E. coli.
      Individual strains of each pathotype possess a distinct set of virulence
      associated characteristics that determine the clinical, pathological and
      epidemiological features of the diseases they cause. In the present brief review,
      we summarize the key distinguishing features of the major pathotypes of
      diarrheagenic E. coli. Knowledge of the pathogenic mechanisms of these bacteria
      has led to the development of rational interventions for the treatment and
      prevention of E. coli-induced diarrhea. In addition, investigations into E. coli
      virulence are providing useful insights into the origins and evolution of
      bacterial pathogens more generally.

PMID- 11982730
TI  - Hepatitis C in childhood.
AB  - The approach of a pediatric hepatologist in managing children with hepatitis C
      virus (HCV) differs from adult practice, because the pediatric hepatologist is
      dealing with the beginning of a chronic illness in which long-term outcomes will
      not occur for 20 or 40 years, and it is not possible to predict in the early
      stages of the infection which patients have a more sinister prognosis. The
      prevalence of chronic HCV in children is low, but varies between different
      countries in the Asia-Pacific region. In most countries, screening of blood
      products for HCV has virtually eliminated the risk of post-transfusion HCV, so
      that in Australia children aged less than 11 years will not have acquired HCV
      from blood transfusion or extracorporeal membrane oxygenation. The risk of
      perinatal transmission of this virus is only about 6%, but this remains virtually
      the only source of HCV transmission for children in most countries. While
      available data are limited, mild histological changes are present in the majority
      of children with hepatitis C, and cirrhosis is rare. Unfortunately, long-term
      natural history studies of the course of HCV infection in children have not been
      reported. Individual decisions on antiviral treatment are more difficult in
      childhood, not because the treatment is any less effective or because of the
      severity of side-effects (which tend to be less severe than for adults), but
      because the long-term outcome of infection is unclear. At present, treatment
      should be confined to those with significant hepatic fibrosis and continued
      moderate to severe necroinflammatory change. Measures to prevent HCV infection in
      childhood center on whether, as recently suggested, elective cesarean section may
      reduce the risk of transmission. Despite the presence of HCV-RNA in some breast
      milk samples, there is no evidence that breast-feeding confers any risk of HCV
      infection.

PMID- 11982731
TI  - Update on the management of Helicobacter pylori infection, including drug
      resistant organisms.
AB  - Helicobacter pylori infection has many different clinical outcomes. Not all
      infected persons need to be treated. Therefore, indications for treatment have to
      be clear, and several consensus guidelines have been formulated to aid the
      medical practitioner in this decision-making process. Triple therapy with a
      proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin
      is the established treatment of choice. For patients with penicillin
      hypersensitivity, metronidazole can be substituted for amoxicillin. Bacterial
      resistance to antibiotics is a major factor adversely affecting treatment
      success. Resistance to metronidazole has been reported in up to 80%, and
      resistance to clarithromycin in 2-10% of strains cultured. Resistance to either
      one of the antibiotics has been reported to result in a drop in efficacy of up to
      50%. Emergence of resistance to both metronidazole and clarithromycin following
      failed therapy is a cause for concern; this underlines the need to use the best
      available first-line therapy. To avoid the emergence of resistance to both key
      antibiotics, the combination of metronidazole and clarithromycin should be
      avoided where possible. For failed treatment, several strategies can be employed.
      These include ensuring better compliance with repeat therapy, and maximizing the
      efficacy of repeat treatment by increasing dosage and duration of treatment, as
      well as altering the choice of drugs. Quadruple therapy incorporating a bismuth
      compound with a PPI, tetracycline and metronidazole has been a popular choice as
      a "rescue" therapy. Ranitidine bismuth citrate has been shown to be able to
      overcome metronidazole and clarithromycin resistance; it may be a useful compound
      drug to use in place of a PPI in "rescue" therapies. In the case of persistent
      treatment failures, it is useful to consider repeating gastroscopy and obtaining
      tissue for culture, and then prescribe antibiotics according to bacterial
      susceptibility patterns. It is also important in refractory cases to review the
      original indication for treatment and determine the importance of the indication.

PMID- 11982732
TI  - Management of peptic ulcer disease not related to Helicobacter.
AB  - Most peptic ulcers not due to Helicobacter pylori are caused by non-steroidal
      anti-inflammatory drugs (NSAID), among which an important subset are due to
      vascular protective ("low-dose") aspirin therapy. Non-steroidal anti-inflammatory
      drugs ulcers heal quite quickly when treated with a proton pump inhibitor (PPI),
      even though the NSAID is continued. If the NSAID can be stopped, the ulcers heal
      readily with either a PPI or a histamine H2-receptor antagonist (H2-RA). If anti
      inflammatory treatment is still needed after ulcers are healed, prophylactic co
      therapy with a PPI or misoprostol will reduce the risk of ulcer recurrence by
      about 60-80%. The alternative of switching to a highly selective cyclooxygenase-2
      inhibitor has been shown to reduce the risk of a complicated ulcer by about 50
      60%, unless low-dose aspirin treatment needs to be given as well for vascular
      disease. Idiopathic ulcers are becoming more frequent as H. pylori prevalence
      falls. Some may be sequelae of previous NSAID ulceration even though the NSAID
      has been ceased and the original ulcer had healed. These are best treated with an
      H2-RA or a PPI, followed by long-term maintenance with either of these (often in
      half the healing dosage) to prevent recurrence. Ulcers due to Zollinger-Ellison
      syndrome and other hypergastrinemia syndromes are rare, and largely beyond the
      scope of this review.

PMID- 11982733
TI  - Gastric cancer: laboratory bench to clinic.
AB  - Gastric cancer is the second most common cause of cancer-related mortality
      worldwide and the 14th overall cause of death. Detection of disease usually
      occurs at an advanced stage and overall survival rates for gastric cancer are
      poor. Our current model for gastric cancer progression clearly maintains
      Helicobacter infection as the primary inducer of gastric metaplastic and
      neoplastic disease. Helicobacter pylori is a ubiquitous organism, infecting more
      than half the world's population. It has been suggested that this infection
      directly contributes to the formation of gastric cancer in up to 80% of cases;
      however, gastric malignancy develops in only a subset (< 1%) of infected
      patients. Therefore, predisposition to Helicobacter-associated gastric cancer is
      most likely multifactorial, including the interaction of bacterial, host and
      environmental components. Our understanding of how the organism interacts with
      the gastric mucosa and synergizes with dietary and other environmental factors to
      induce malignant mucosal changes is evolving. Indeed, H. pylori has direct
      effects on the gastric mucosa, but the major factor in disease progression
      appears to be a robust host Th1 immune response in the setting of a permissive
      environment. In combination, these factors predispose to the formation of
      atrophy, metaplasia and gastric cancer. Understanding the interaction of the
      bacterium with the host and the environment can potentially identify patients
      most at risk. Identifying potentially removable factors (in addition to H. pylori
      infection) in the acquisition and progression of neoplastic disease may provide
      targets for early intervention and prevention strategies.

PMID- 11982734
TI  - Advances in the management of irritable bowel syndrome.
AB  - Recent advances in different aspects of irritable bowel syndrome have led to a
      need to reassess the overall management of this common, complex disorder.
      Important areas include: first, the heterogeneity of symptom patterns and the
      role of specific diagnostic symptom criteria for use in both clinical practice
      and in clinical research; second, the growing interest in the potential
      interaction between "peripheral" and "central" pathophysiological mechanisms; and
      third, the development of novel and effective drugs designed to target specific
      receptor systems in the enteric nervous system. This review covers each of these
      aspects and emphasizes an approach to management of patients based on
      pathophysiological considerations.

PMID- 11982736
TI  - Who cares about the obese hypertensive patient?

PMID- 11982735
TI  - Chronic pancreatitis: Asia-Pacific consensus report.
AB  - Current knowledge about chronic pancreatitis (CP) is limited and there is a
      particular dearth of information about the entity known as tropical pancreatitis.
      A consensus working party was convened by the Trustees of the Journal of
      Gastroenterology and Hepatology Foundation to conduct a systematic investigation
      into available evidence about the epidemiology, etiopathogenesis, diagnosis and
      management of CP. A literature search and formal survey of international experts
      in the field were used to assemble reliable evidence about these issues. The
      present review summarizes the results of the working party's findings and
      presents a series of practice guidelines to improve diagnosis, investigation and
      treatment of patients with CP, particularly those in the Asia-Pacific region.
      Areas for further research have also been identified.

PMID- 11982737
TI  - Antioxidant vitamins in the prevention of cardiovascular disease: a systematic
      review.
AB  - Do antioxidant vitamins, in regular food or as food supplements, protect against
      myocardial infarction and stroke? In this systematic literature review on the
      effects of antioxidant vitamins in the primary prevention of cardiovascular
      disorders, studies with ischaemic heart disease, stroke or combined
      cardiovascular events as end-points have been included. Studies on the effects of
      antioxidant vitamins on intermediary end-points (such as blood lipids and blood
      pressure) and as secondary prevention in patients with manifest cardiovascular
      disease are reviewed in a conventional manner. In observational studies (case
      control or cohort design), people with high intake of antioxidant vitamins by
      regular diet or as food supplements generally have a lower risk of myocardial
      infarction and stroke than people who are low-consumers of antioxidant vitamins.
      The associations in observation studies have been shown for carotene, ascorbic
      acid as well as tocopherol. In randomized controlled trials, however, antioxidant
      vitamins as food supplements have no beneficial effects in the primary prevention
      of myocardial infarction and stroke. Serious adverse events have been reported.
      After an initial enthusiasm for antioxidants in the secondary prevention of
      cardiovascular disease, recent reports from of several large randomized trials
      have failed to show any beneficial effects. Thus, the apparent beneficial results
      of high intake of antioxidant vitamins reported in observational studies have not
      been confirmed in large randomized trials. The discrepancy between different
      types of studies is probably explained by the fact that supplement use is a
      component in a cluster of healthy behaviour. Antioxidant vitamins as food
      supplements cannot be recommended in the primary or secondary prevention against
      cardiovascular disease.

PMID- 11982738
TI  - Body position and blood pressure measurement in patients with diabetes mellitus.
AB  - AIMS: World Health Organization (WHO) guidelines recommend that the blood
      pressure (BP) should be routinely measured in sitting or supine followed by
      standing position, providing that the arm of the patient is placed at the level
      of the right atrium in each position. The aim of our study was to test the
      influence of body and arm position on BP measurement in diabetic patients.
      METHODS: In 142 patients with diabetes mellitus the BP was measured using a
      semiautomatic oscillometric device (Bosomat-R): (i) after 5 min of rest sitting
      on a chair with one arm supported at the right atrial level and with the other
      arm placed on the arm support of the chair, (ii) after 5 min of rest lying on a
      bed with both arms placed on a bed, and (iii) after 30 s and after 2 min of
      standing with one arm (the same as in sitting position) supported at the right
      atrial level and with the other arm vertical, parallel to the body. RESULTS: Both
      systolic (SBP) and diastolic (DBP) blood pressures were significantly lower in
      sitting position with the arm at the right atrial level than in supine position
      (by 7.4 and 6.6 mmHg, respectively, P < 0.01). In sitting and standing positions,
      SBP and DBP were higher when the arm was placed either on the arm support of the
      chair or vertical, parallel to the body, than when the arm was supported at the
      level of the right atrium (by 6-10 mmHg, P < 0.001). Duration of standing did not
      influence the estimation of orthostatic hypotension. CONCLUSIONS: The data of
      this study indicate that the WHO recommendation with regard to the equivalence of
      sitting and supine BP readings is incorrect at least in diabetic patients, as the
      sitting BP is lower than the supine BP when the arm was positioned at the right
      atrial level. In addition, incorrect positioning of the arm in standing position
      results in an underestimation of prevalence of orthostatic hypotension. We
      conclude that during BP measurement the arm should be placed at the right atrial
      level regardless of the body position.

PMID- 11982739
TI  - Thyroid dysfunction during treatment of chronic hepatitis C with interferon
      alpha: no association with either interferon dosage or efficacy of therapy.
AB  - OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha)
      may induce thyroid disorders. We evaluated whether this risk is related to the
      dosage of IFN-alpha or the virological treatment response. Other possible risk
      factors as well as the evolution of the thyroid abnormalities were also studied.
      METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH),
      free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before,
      during and after treatment for hepatitis C virus (HCV). The patients were
      randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for
      4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU
      3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or
      1200 mg) daily. Sustained virological response was defined as loss of detectable
      HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below
      or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid
      dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5
      MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients.
      Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment
      was discontinued because of thyroid dysfunction in three of these patients.
      Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose
      IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who
      received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who
      completed all 6 months of HCV treatment, a sustained virological response was
      obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without
      (P=0.24). By multivariate analysis female gender and Asian origin were
      independent predictors of developing biochemical thyroid dysfunction (P < 0.01).
      CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic
      hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the
      virological response to treatment were related to the incidence of thyroid
      dysfunction.

PMID- 11982740
TI  - Treatment of benign nodular goitre with mildly suppressive doses of L-thyroxine:
      effects on bone mineral density and on nodule size.
AB  - OBJECTIVES: To evaluate (i) the demineralizing effect of L-thyroxine (LT4)
      therapy at doses mildly inhibiting serum thyroid stimulating hormone (TSH) in
      patients with benign nodular goitre; (ii) the efficacy of treatment on nodule
      size. DESIGN: Cross-sectional study comparing euthyroid women with nodular goitre
      treated with LT4 for > or = 2 years (52 +/- 32 months, range 24-138, median 42)
      and a matched group with untreated goitre. SUBJECTS: A total of 89 female
      outpatients (53.3 +/- 9 years; 36 pre- and 53 postmenopausal), 43 treated and 46
      untreated. MAIN OUTCOME MEASURES: Bone mineralization was measured with total
      body and regional mineralometry [dual energy X-ray absorptiometry (DEXA)], and
      indirectly evaluated with biochemical parameters (alkaline phosphatase,
      osteocalcin). Efficacy of LT4 therapy was assessed by measuring the nodule size
      during ultrasonography. The adequacy of the treatment was evaluated on the basis
      of serum TSH levels. RESULTS: No significant differences were found at DEXA for
      total body and regional mineralization (P > 0.05 for all comparisons) in treated
      and untreated patients, both in pre- and postmenopausal states. Evaluation of the
      nodule size during the ultrasound scan showed a reduction of > or = 30% in 11 of
      43 treated patients (26%) versus none of the untreated, an unchanged size in 29
      treated patients (67%) versus 18 untreated, an increase of nodules and/or new
      nodule development in three treated patients (7%) versus 28 untreated (61%).
      CONCLUSIONS: L-thyroxine (LT4) treatment at doses slightly suppressing TSH does
      not significantly affect bone mineralization, nor does it represent a risk factor
      for osteoporosis, even in postmenopausal patients. The efficacy of this
      therapeutic schedule on goitre size is comparable with the effects previously
      reported with suppressive doses.

PMID- 11982741
TI  - Left ventricular diastolic function is related to glucose in a middle-aged
      population.
AB  - OBJECTIVES: To examine the relation between left ventricular (LV) diastolic
      function and glucose metabolism in individuals without previously diagnosed
      diabetes mellitus. DESIGN: A cross-sectional population-based study. SETTING: A
      university hospital. SUBJECTS: Thirty-five men and women 56-58 years of age
      without previously diagnosed diabetes or heart disease. MAIN OUTCOME MEASURES:
      Left ventricular diastolic function assessed by pulsed Doppler tissue imaging and
      its relation to fasting plasma glucose, glucose postload and glycated
      haemoglobin. LV diastolic function was determined by measuring early diastolic
      filling peak velocity (Em wave cm s-1), late diastolic filling peak velocity (Am
      wave cm s-1) and their ratio Em/Am. RESULTS: Peak Em velocity, peak Am velocity
      and their ratio Em/Am correlated with fasting plasma glucose (r=-0.42, P=0.01;
      r=0.47, P=0.04 and r=-0.53, P=0.001, respectively). There was a correlation
      between peak Em velocity, the ratio of Em/Am and glycated haemoglobin. LV
      diastolic function was also related to glucose postload. CONCLUSIONS: Left
      ventricular diastolic function is related to concentrations of fasting plasma
      glucose, glucose postload and glycated haemoglobin even below the threshold of
      diabetes. This indicates that glucose concentrations already in the upper end of
      the normal range has negative impact on cardiac function.

PMID- 11982742
TI  - Effect of medroxyprogesterone on pulmonary arterial pressure, exhaled nitric
      oxide, ECG and arterial blood gases.
AB  - OBJECTIVES: To evaluate the effect of medroxyprogesterone acetate (MPA) therapy
      on pulmonary arterial pressure (PAP), exhaled nitric oxide (NO),
      electrocardiogram (ECG), and on arterial blood gases (ABG). DESIGN: A double
      blind randomized placebo-controlled cross-over trial. SETTING: University
      hospital in Turku, Finland. SUBJECTS: Fourteen postmenopausal women with
      respiratory impairment. INTERVENTIONS: A 2-week placebo and a 2-week MPA period
      (60 mg day -1) followed by 6-week placebo or MPA washout periods. MAIN OUTCOME
      MEASURES: The systolic PAP was estimated by Doppler echocardiography. PAP, ECG,
      NO and ABG were monitored at baseline, after 2-week placebo and MPA periods, and
      after 3- and 6-week placebo and MPA washout periods. RESULTS: The mean PaCO2 at
      baseline was 5.4 +/- 0.6 kPa (mean +/- SD). The average decrease of PaCO2 on MPA
      was -0.8 +/- 0.3 kPa (P < 0.001) and 0.3 +/- 1.0 kPa (P = 0.007) at the 3-week
      washout. The mean systolic PAP at baseline was 44.3 +/- 14.5 mm Hg. MPA did not
      change PAP until the 6-week washout, when the average increase of + 6.9 +/- 19.8
      mm Hg (P = 0.002) was observed. No changes occurred in PaO2, exhaled NO or the
      ECG axes. The PR interval was shorter only on MPA (15.9 +/- 27.0 ms, P = 0.020)
      whereas the QRS duration remained shorter up to 3-week washout (3.9 +/0 5.5 ms, P
      = 0.008 and 4.0 +/- 14.3 ms, P = 0.032). The systolic and diastolic BP and the
      heart rate did not change. CONCLUSIONS: Despite prolonged decrease in PaCO2,
      short-term MPA had no effect on exhaled NO and did not decrease systolic PAP in
      postmenopausal women with respiratory impairment. MPA shortened the PR interval
      and the QRS duration, the latter effect being sustained at least up to 3 weeks.

PMID- 11982743
TI  - Lipoprotein lipase polymorphisms and responses to long-term overfeeding.
AB  - OBJECTIVES: The role of the lipoprotein lipase (LPL) gene Hind III, S447X, Bam HI
      and Pvu II polymorphisms on body composition and lipid and lipoprotein changes in
      response to long-term overfeeding was studied. SUBJECTS: Twelve pairs of male
      monozygotic twins ate a 4.2 MJ day-1 energy surplus, 6 days a week, during a
      period of 100 days. RESULTS: Overfeeding induced a decrease in high-density
      lipoprotein 2 cholesterol (HDL2-C) and HDL2-C to HDL3-C ratio in the H2H2 (n =
      12) subjects of the LPL Hind III polymorphism. In contrast, the H1H1/H1H2 (n =
      12) subjects experienced increases both in the HDL2-C and HDL2-C to HDL3-C ratio
      (P = 0.009 and 0.007, respectively, for differences in percentage changes between
      H2H2 and H1H1/H1H2). In addition, the H2H2 genotype was associated with higher
      levels of very-low-density lipoprotein triglyceride (VLDL-TG) (P < 0.03) and VLDL
      C (P < 0.05) before and after overfeeding and higher HDL-TG levels (P < 0.003)
      after overfeeding. Postheparin lipoprotein lipase (PH-LPL) activity tended to
      increase in H1H1/H1H2 and decrease in H2H2 subjects. The H2H2 subjects had lower
      total HDL-C than those with the genotype H1H1/H1H2 4 months and 5 years after
      overfeeding (P = 0.04 and 0.10, respectively). The plasma lipid differences were
      similar amongst subjects with the S447S (n = 4) genotype of the S447X and H2H2
      genotype of the Hind III polymorphisms. Body composition changes in response to
      overfeeding were not different between the Hind III genotypes. LPL Pvu II and
      Hind III polymorphisms were associated weakly with body weight gain (P = 0.015
      0.039) but strongly with adipose tissue LPL activity (P < 0.01) after the caloric
      surplus. CONCLUSIONS: We conclude that the H2H2 subjects of the LPL gene Hind III
      polymorphism experience a decrease in the concentration of antiaterogenic
      lipoproteins when they are exposed to long-term positive energy balance. This may
      have been partly caused by a diminished catabolism of TG-rich particles in H2H2
      subjects. LPL Pvu II and Bam HI polymorphisms were associated with body weight
      gain and adipose tissue LPL activity. Genetic variation at the LPL locus could
      thus be one of the factors responsible for the inter-individual differences
      observed in plasma lipid and lipoprotein responses to chronic positive energy
      balance. It must be kept in mind that the sample size for this study was small.
      Nonetheless, it provides useful information on the genes and pathways that should
      be further explored.

PMID- 11982744
TI  - Inhibitory effects of N-acetylcysteine on scavenger receptor class A expression
      in human macrophages.
AB  - OBJECTIVE: The formation of foam cells from monocyte-derived macrophages involves
      the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit
      lipoprotein oxidation and may also modulate gene expression. We investigated the
      effect of the antioxidant N-acetylcysteine on the expression of the class A
      scavenger receptor (SR-A) types I and II in human macrophages. DESIGN: Monocytes
      and macrophages from healthy blood donors and plaque-derived macrophages from
      patients undergoing carotid endarterectomy were used for experiments. SR-A mRNA
      was analysed with quantitative and semiquantitative reverse transcription
      polymerase chain reaction, and ligand binding and uptake were assessed with 125I
      labelled acetylated low-density lipoprotein (LDL). RESULTS: Incubation of
      monocytes and monocyte-derived macrophages with N-acetylcysteine decreased both
      SR-A I and II mRNA expression. N-Acetylcysteine also reduced SR-A mRNA in lesion
      derived cells. Binding and uptake of 125I-acetylated LDL was decreased after
      brief incubation with N-acetylcysteine. After longer periods of incubation with N
      acetylcysteine we observed an increased degradation of lipoproteins. CONCLUSIONS:
      Our results imply that N-acetylcysteine leads to a decrease in SR-A mRNA and
      initially also to an attenuated uptake of modified lipoproteins. This adds more
      to the knowledge about the cellular actions of this drug.

PMID- 11982745
TI  - A family with IgA nephropathy and hereditary lymphoedema praecox.
AB  - Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis
      worldwide. The pathogenesis is still unknown and treatment has not yet been
      established. Rarely it can be associated with other disorders. Its association
      with hereditary lymphoedema is not reported before. We report four patients, a 60
      year-old father, his two sons and his daughter, with hereditary lymphoedema. The
      family had nine members and in four of them lymphoedema was evident. The other
      members had neither lymphoedema nor IgA nephropathy. This is the first report of
      IgA nephropathy in association with hereditary lymphoedema.

PMID- 11982746
TI  - Statins and the assessment of endothelial function.

PMID- 11982749
TI  - In this issue extra--light of my life.

PMID- 11982750
TI  - Searching for the major histocompatibility complex psoriasis susceptibility gene.
AB  - Psoriasis, a common skin disorder, is widely regarded to be multifactorial in
      origin including gene-gene and gene-environment interactions. Genetic and allelic
      heterogeneity, multifactorial inheritance, and low penetrance of susceptibility
      alleles substantially complicate both study design and interpretation of results.
      Notwithstanding these difficulties, genome-wide scans for psoriasis
      susceptibility have generated robust evidence for a major locus lying within the
      major histocompatibility complex (PSORS1, Psoriasis Susceptibility 1), on the
      short arm of chromosome 6. Subsequent studies have sought to refine the PSORS1
      boundaries by means of linkage disequilibrium fine mapping. Studies of positional
      candidate genes have also been undertaken, focusing on HLA-C, corneodesmosin, and
      alpha-helix coiled-coil rod homolog genes. Methodologic approaches, results, and
      interpretations of these studies are discussed, as well as future research
      objectives. In particular, we emphasize the importance of characterizing PSORS1
      linkage disequilibrium patterns and developing functional assays for disease
      associated alleles.

PMID- 11982751
TI  - Aging and survival of cutaneous microvasculature.
AB  - The growth and turnover of blood vessels in the skin is fundamental in normal
      development, wound repair, hair follicle cycling, tumor cell metastasis, and in
      many different states of cutaneous pathology. Whereas many investigations are
      focused on mechanisms of angiogenesis in the skin, the influence of cellular
      aging and replicative senescence (i.e., the inability, after a critical number of
      population doublings, to replicate) on microvascular remodeling events has
      received relatively less attention. In this article, we review the clinical and
      pathologic relationships associated with cutaneous vascular aging and update
      current knowledge of endothelial cell survival characteristics. A hypothesis is
      presented in which endothelial cell aging and survival are linked to molecular
      mechanisms controlling cell proliferation, quiescence, apoptosis, and cellular
      senescence. We review recent results demonstrating how activation of telomerase
      in human dermal microvascular endothelial cells affects their durability both in
      vitro and in vivo and conclude by linking these studies with current concepts
      involving endothelial cell precursors, control of postnatal somatic cell
      telomerase activity, and murine model systems.

PMID- 11982752
TI  - Stromelysin-1 activation correlates with invasiveness in squamous cell carcinoma.
AB  - The expression of selected metalloproteinases and tissue inhibitors of
      metalloproteinases (TIMP) was examined in three squamous cell carcinoma (SCC)
      cell lines (FaDu, SiHa, A431) and a keratinocyte cell line (HaCaT) to determine
      which metalloproteinases function in SCC invasiveness. A Matrigel invasion assay
      was used to assess invasiveness of the cell lines. Only the FaDu cell line showed
      invasiveness in this assay, and invasion of Matrigel by FaDu cells was inhibited
      by treatment with the metalloproteinase inhibitor, batimastat. No correlation was
      found between mRNA expression for matrilysin, stromelysins 1-3, TIMP-1, or TIMP-3
      and secretion of these proteins, indicating that the extracellular activity of
      these molecules is regulated post-transcriptionally. The SCC cell lines differed
      from the HaCaT line in that matrilysin and TIMP-1 proteins were detected in
      conditioned medium from all SCC cell lines, but not in medium from HaCaT cells.
      Only the invasive cell line, FaDu, released active stromelysin-1 into the culture
      medium. These results indicate that while matrilysin contributes to the invasive
      phenotype, activation of stromelysin-1 is a key regulatory step for invasiveness
      in SCC cells.

PMID- 11982753
TI  - Overexpression of IL-4 alters the homeostasis in the skin.
AB  - IL-4 has been implicated to play an important role in the pathogenesis of many
      inflammatory diseases including skin diseases such as atopic dermatitis. Because
      it is not clear which pathologic features of atopic dermatitis are dependent on
      IL-4, we assessed the consequences of IL-4 overexpression in the skin, using
      transgenic mice overexpressing IL-4 ubiquitously. Although transgenic mice
      display no clinical signs of skin inflammation, IL-4 induced a wide spectrum of
      pathologies including an increased number of mast cells and Langerhans cells in
      dermis and epidermis, respectively, focal deposition of collagen and a
      considerably reduced adipocyte layer in the dermis as well as an increased
      mitotic activity of keratinocytes, reflected in acanthosis and hyperkeratosis.
      The increase in Langerhans cell number may be explained in part by the
      substantially reduced Langerhans cell emigration from the epidermis in transgenic
      mice. The molecular mechanism behind this phenomenon remains to be clarified.
      Under in vitro culture conditions, Langerhans cells from transgenic mice undergo
      a maturation process similar to that of Langerhans cells from control mice, and
      their immunostimulatory capacity is also comparable. In contrast, transgenic
      Langerhans cells are superior to control Langerhans cells in their antigen
      processing capacity. We conclude that the overexpression of IL-4 in the skin is,
      by itself, not sufficient for the induction of a full-blown atopic dermatitis
      phenotype, but several changes seen in the skin of transgenic mice mirror the
      cardinal pathologic manifestations of this disease.

PMID- 11982754
TI  - Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of
      calcineurin/NFAT activation in human keratinocytes by cyclosporin A.
AB  - Systemic cyclosporin A and tacrolimus are effective treatments for psoriasis.
      Cyclosporin A and tacrolimus block T cell activation by inhibiting the
      phosphatase calcineurin and preventing translocation from the cytoplasm to the
      nucleus of the transcription factor nuclear factor of activated T cells (NFAT).
      Inhibition of T cell activation is thought to account for their therapeutic
      action in psoriasis. We investigated whether nonimmune cells in human skin
      express calcineurin and NFAT1 and whether cyclosporin A and tacrolimus block
      activation of calcineurin/NFAT in epidermal keratinocytes. The expression
      patterns of the principal components of calcineurin/NFAT signaling pathway in
      normal human skin and psoriasis were determined by immunohistochemistry. We
      assessed calcineurin/NFAT activation in cultured keratinocytes by measuring the
      degree of nuclear localization of calcineurin and NFAT1 using
      immunofluorescence/confocal microscopy and assessed if cyclosporin A and
      tacrolimus blocked nuclear translocation of these proteins. A variety of cell
      types in normal and psoriatic skin expressed calcineurin and NFAT1, but
      expression was particularly prominent in keratinocytes. The principal cyclosporin
      A and tacrolimus binding proteins cyclophilin A and FKBP12 were also expressed by
      keratinocytes and nonimmune cells in skin. NFAT1 was predominantly nuclear in
      normal basal epidermal keratinocytes. Increased nuclear localization of NFAT1 was
      observed in suprabasal keratinocytes within lesional and to a lesser extent
      nonlesional psoriatic epidermis compared to normal skin (p = 0.001 and p = 0.03,
      respectively), suggesting increased activation of calcineurin in psoriatic
      epidermal keratinocytes. Agonists that induce keratinocyte differentiation,
      specifically 12-0-tetradecanoyl-phorbol-13-acetate (TPA) plus ionomycin, TPA, and
      raised extracellular calcium, induced nuclear translocation of NFAT1 and
      calcineurin in keratinocytes that was inhibited by pretreatment with cyclosporin
      A or tacrolimus. In contrast in human dermal fibroblasts, TPA plus ionomycin or
      TPA did not significantly alter the proportion of nuclear-associated NFAT1. These
      data provide the first evidence that calcineurin is functionally active in human
      keratinocytes inducing nuclear translocation of NFAT1 and also indicate that
      regulation of NFAT1 nuclear translocation in skin is cell type specific.
      Inhibition of this pathway in epidermal keratinocytes may account, in part, for
      the therapeutic effect of cyclosporin A and tacrolimus in skin diseases such as
      psoriasis.

PMID- 11982755
TI  - A novel epithelial keratin, hK6irs1, is expressed differentially in all layers of
      the inner root sheath, including specialized huxley cells (Flugelzellen) of the
      human hair follicle.
AB  - In this study we have characterized a novel human type II keratin, hK6irs1, which
      is specifically expressed in the inner root sheath of the hair follicle. This
      keratin represents the ortholog of the recently described mouse inner root sheath
      keratin mK6irs. The two keratins were highly related and migrated at the same
      height as keratin 6 in two-dimensional gel electrophoresis. Both RNA in situ
      hybridization and indirect immunofluorescence studies of human hair follicles
      demonstrated hK6irs1 expression in the Henle and Huxley layers as well as in the
      cuticle of the inner root sheath. In all three layers, the expression of hK6irs1
      mRNA and protein began simultaneously in adjacent cells of the lowermost bulb
      above the germinative cell pool. Higher up in the follicle, the detection limits
      for both hK6irs1 mRNA and protein precisely coincided with the asynchronous onset
      of abrupt terminal differentiation of the Henle layer, inner root sheath cuticle,
      and Huxley layer. Mainly above the level of terminal Henle cell differentiation,
      both indirect immunofluorescence and immunoelectron microscopy revealed the
      occurrence of distinct Huxley cells that developed pseudopodal hK6irs1-positive
      extensions passing through the fully keratinized Henle layer. These outwardly
      protruding foot processes abutted upon cells of the companion layer, with which
      they were connected by numerous desmosomes. These specialized Huxley cells have
      previously been termed "Flugelzellen", which means "winged cells", with reference
      to their characteristic foot processes. We provide evidence that, together with
      Henle cells, Flugelzellen ensure the maintenance of a continuous desmosomal
      anchorage of the companion layer along the entire inner root sheath. This tightly
      connected companion layer/inner root sheath unit provides an optimal molding and
      guidance of the growing hair shaft.

PMID- 11982756
TI  - Targeted overexpression of the angiogenesis inhibitor thrombospondin-1 in the
      epidermis of transgenic mice prevents ultraviolet-B-induced angiogenesis and
      cutaneous photo-damage.
AB  - Chronic ultraviolet-B irradiation of the skin results in epidermal hyperplasia,
      degradation of extracellular matrix molecules, and formation of wrinkles. To
      characterize the biologic role of the vascular system in the mediation of
      ultraviolet-B-induced skin damage, we performed quantitative analyses of
      cutaneous blood vessels of mice after 10 wk of ultraviolet-B irradiation. Skin
      vascularization was greatly increased after chronic ultraviolet-B exposure with a
      significant increase of both the number and the size of dermal blood vessels,
      associated with upregulation of vascular endothelial growth factor expression in
      the hyperplastic epidermis. To directly study whether inhibition of angiogenesis
      may diminish ultraviolet-B-induced cutaneous damage, wild-type and transgenic
      mice with skin-specific overexpression of the endogenous angiogenesis inhibitor
      thrombospondin-1 were subjected to the same ultraviolet-B irradiation regimen.
      Ultraviolet-B-irradiated thrombospondin-1 transgenic mice showed a significantly
      reduced skin vascularization, decreased endothelial cell proliferation, and
      increased endothelial cell apoptosis rates, compared with wild-type mice.
      Moreover, dermal photo-damage and wrinkle formation were greatly reduced in
      thrombospondin-1 transgenic mice. These results reveal an important role of the
      cutaneous vascular system in mediating ultraviolet-B-induced skin damage and
      suggest inhibition of angiogenesis as a potential new approach for the prevention
      of chronic cutaneous photo-damage.

PMID- 11982757
TI  - A subset of pemphigus foliaceus patients exhibits pathogenic autoantibodies
      against both desmoglein-1 and desmoglein-3.
AB  - In pemphigus vulgaris the major pathogenic antibody binds desmoglein-3, and
      mediates mucosal disease. Development of cutaneous disease is associated with
      acquisition of antibodies to desmoglein-1. In pemphigus foliaceus, and its
      endemic form, fogo selvagem by contrast, the major pathogenic antibody recognizes
      desmoglein-1 and mediates cutaneous disease only. In this study, we sought to
      determine the prevalence of antibodies to desmoglein-3 in patients with pemphigus
      foliaceus and fogo selvagem. We produced recombinant desmoglein-1 and desmoglein
      3, and used them in highly sensitive and specific enzyme-linked immunosorbent
      assays, as well as immunoprecipitation assays. We detected antibodies to
      desmoglein-3 in 19 of 276 patients with pemphigus foliaceus and fogo selvagem,
      who had cutaneous disease only. We showed that these antibodies to desmoglein-3
      could be absorbed in a concentration-dependent manner by desmoglein-3 but not by
      desmoglein-1. Also antibodies to desmoglein-1 could be absorbed in a
      concentration-dependent manner by desmoglein-1 but not desmoglein-3. This
      suggests that two separate species of antibody are present rather than one
      antibody capable of cross-reacting with both desmoglein-1 and desmoglein-3.
      Finally, it was shown that affinity-purified antibodies to desmoglein-3 from
      patients with pemphigus foliaceus and fogo selvagem induced a pemphigus vulgaris
      like skin disease in mice by passive transfer. These results suggest that a
      subset of patients with pemphigus foliaceus and fogo selvagem have antibodies to
      desmoglein-3 that may be involved in the pathogenesis of their cutaneous disease.

PMID- 11982758
TI  - Epidermal langerhans cell depletion after artificial ultraviolet B irradiation of
      human skin in vivo: apoptosis versus migration.
AB  - Ultraviolet B radiation can suppress cellular immunity. One of the mechanisms
      related to this immunosuppression is the disappearance of Langerhans cells from
      the epidermis. The aim of this study was to establish the mechanism of
      ultraviolet B-induced Langerhans cell disappearance in healthy individuals. The
      two most likely mechanisms for Langerhans cell disappearance are apoptosis and
      migration. Apoptosis was assessed in vivo by exposing buttock skin of 10 healthy
      volunteers to six minimal erythema doses of ultraviolet B. Only very few
      apoptotic Langerhans cells could be observed in sections from the ultraviolet B
      exposed skin. Migration of Langerhans cells cannot be established in skin
      sections and suction blisters were therefore raised in an attempt to trap
      migrating Langerhans cells in the sub-basal membrane blister fluid. Blisters were
      raised on the flexor side of the lower arm of 30 healthy volunteers at several
      time points after exposure of the skin to six minimal erythema doses of
      ultraviolet B. Blister fluid was collected and blister roofs were removed to
      check for Langerhans cell disappearance. Langerhans cells were detected in the
      blister fluid of the ultraviolet B-exposed skin and not of the unexposed skin.
      The number of Langerhans cells in the blister fluid peaked at about 18 h after
      ultraviolet exposure, which coincided with the largest depletion of Langerhans
      cells in the blister roof. A fraction (20-30%) of the Langerhans cells in the
      blister fluid stained positive for DNA damage (cyclobutyl pyrimidine dimers),
      showing that they originated from the epidermis. Ultraviolet B-induced Langerhans
      cell disappearance appears to be mainly attributable to migration.

PMID- 11982759
TI  - Ultraviolet-B-induced G1 arrest is mediated by downregulation of cyclin-dependent
      kinase 4 in transformed keratinocytes lacking functional p53.
AB  - In order to identify potential novel targets for ultraviolet-B-induced skin
      tumorigenesis, we assessed the effect of ultraviolet-B exposure on cell cycle
      progression of transformed keratinocytes with mutant p53. We show that
      ultraviolet-B exposure of human epidermoid carcinoma A431 cells results in G1
      cell cycle arrest in both asynchronously growing and synchronized cells. A
      significant increase in G1 cell population was observed following exposure to
      doses of ultraviolet-B as low as 10 mJ per cm2. When irradiated with ultraviolet
      B, cells synchronized in G1 with mimosine did not exit G1. G1 cell cycle arrest
      was associated with a decrease in the hyperphosphorylated forms of retinoblastoma
      protein that was detectable within 4 h and gradually disappeared by 12 h. We also
      observed a decrease in cyclins D1, D2, and D3, and cyclin-dependent kinase 4
      proteins, and a concomitant decrease in cyclin-dependent kinase 4/cyclin D1
      associated kinase activity, whereas ultraviolet-B exposure had no effect on
      cyclin-dependent kinase 2 and cyclin-dependent kinase 6 levels during this time
      period. Incubation of cells with proteasome inhibitors MG-115 and MG-132
      prevented the decrease in cyclin D1, D2, and D3, and cyclin-dependent kinase 4
      protein. Taken together, our results suggest that ultraviolet-B-induced cell
      cycle arrest in A431 cells is mediated by cyclin-dependent kinase 4
      downregulation. This identifies a novel pathway for G1 cell cycle arrest in
      transformed keratinocytes following ultraviolet-B irradiation.

PMID- 11982760
TI  - Repeated ultraviolet exposure affords the same protection against DNA photodamage
      and erythema in human skin types II and IV but is associated with faster DNA
      repair in skin type IV.
AB  - We have investigated the photoprotective properties of induced pigmentation using
      erythema and epidermal DNA photodamage as endpoints. Previously unexposed buttock
      skin of 12 young, healthy adults (six skin type II and six skin type IV) was
      exposed daily (Monday to Friday) for 2 wk (days 1-12) with 0.65 minimal erythema
      dose of solar simulated radiation. Mean skin type IV minimal erythema dose was
      1.8-fold greater than for skin type II. Compared to skin type II, solar simulated
      radiation treatments produced less erythema and more tanning in skin type IV. To
      assess DNA photodamage, biopsies were taken and prepared for paraffin sections
      that were stained with a monoclonal antibody for thymine dimers. Thymine dimers
      were quantified by image analysis. The single exposure data (0.65 and 2 minimal
      erythema dose) showed that DNA damage was related to physical dose (J per cm2)
      independent of skin type. Our data also showed that DNA photodamage accumulates
      in both skin types with repeated, suberythemal doses of solar simulated
      radiation. On day 12, there were more thymine dimers in skin type IV than skin
      type II, again indicating that physical rather than biologic dose determines the
      level of DNA damage. Comparisons on days 12 and 19, however, showed a much
      greater loss of thymine dimers in skin type IV, suggesting better thymine dimer
      repair. Protection factors for erythema and thymine dimers were calculated and
      shown to be about 2 in both skin types. This provides further indirect evidence
      that DNA is a chromophore for erythema, but also suggests that a tan may not be
      the major factor in natural photoprotection.

PMID- 11982761
TI  - Aggregation of the high-affinity IgE receptor Fc(epsilon)RI on human monocytes
      and dendritic cells induces NF-kappaB activation.
AB  - In contrast to mast cells and basophils, the high-affinity IgE receptor
      (Fc(epsilon)RI) on monocytes and dendritic cells (DC), including epidermal
      Langerhans cells, is not constitutively expressed and lacks the beta-chain.
      Fc(epsilon)RI is upregulated on Langerhans cells of atopic individuals,
      particularly in atopic dermatitis skin. Although Fc(epsilon)RI provides IgE
      mediated antigen focusing on monocytes and DC/Langerhans cells, its relevance for
      cell activation remains elusive, and the transcription factors regulating
      Fc(epsilon)RI-induced genes are unknown. We show that NF-kappaB, known to
      regulate genes essential for inflammatory responses and DC differentiation and
      function, is activated upon Fc(epsilon)RI ligation in primary human monocytes and
      DC. In Langerhans cells isolated from epidermis, NF-kappaB activation is
      restricted to donors expressing high Fc(epsilon)RI amounts. Fc(epsilon)RI-induced
      NF-kappaB complexes in monocytes and DC contain p50 and p65, but no other NF
      kappaB subunits despite increased RelB expression during differentiation. NF
      kappaB activation is preceded by serine phosphorylation and degradation of its
      inhibitory protein IkappaB-alpha without involving other IkappaB proteins.
      Finally, we show that Fc(epsilon)RI ligation on monocytes and DC leads to
      synthesis and release of tumor necrosis factor-alpha and monocyte chemoattractant
      protein-1, which is decreased by two mechanistically distinct inhibitors of NF
      kappaB activation. Thus NF-kappaB activation represents a novel mechanism by
      which Fc(epsilon)RI on monocytes and DC potentially controls inflammatory
      reactions.

PMID- 11982762
TI  - Frameshift mutation in the V2 domain of human keratin 1 results in striate
      palmoplantar keratoderma.
AB  - The striate form of palmoplantar keratoderma is a rare autosomal dominant
      disorder affecting palm and sole skin. Genetic heterogeneity of striate
      palmoplantar keratoderma has been demonstrated with pathogenic mutations in the
      desmosomal proteins desmoplakin and desmoglein 1. We have studied a four
      generation family of British descent with striate palmoplantar keratoderma.
      Ultrastructural studies show that intermediate filaments of suprabasal
      keratinocytes are finer than those of the basal layer. In addition, desmosome
      numbers are normal, but their inner plaques and midline structures are
      attenuated. Microsatellite markers were used to screen candidate loci including
      the epidermal differentiation complex on 1q, the desmoplakin locus on 6p, the
      type I and II keratin gene clusters on chromosomes 12q and 17q, and the
      desmosomal cadherin gene cluster on chromosome 18q. Significant genetic linkage
      to chromosome 12q was observed using marker D12S368, with a maximum two-point lod
      score of 3.496 at a recombination fraction of 0. Direct sequencing of the keratin
      1 gene revealed a frameshift mutation in exon 9 that leads to the partial loss of
      the glycine loop motif in the V2 domain and the gain of a novel 70 amino acid
      peptide. Using expression studies we show that the V2 domain is essential for
      normal function of keratin intermediate filaments.

PMID- 11982763
TI  - Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1.
AB  - Staphylococcal scalded skin syndrome and its localized form, bullous impetigo,
      show superficial epidermal blister formation caused by exfoliative toxin A or B
      produced by Staphylococcus aureus. Recently we have demonstrated that exfoliative
      toxin A specifically cleaves desmoglein 1, a desmosomal adhesion molecule, that
      when inactivated results in blisters. In this study we determine the target
      molecule for exfoliative toxin B. Exfoliative toxin B injected in neonatal mice
      caused superficial epidermal blisters, abolished cell surface staining of
      desmoglein 1, and degraded desmoglein 1 without affecting desmoglein 3 or E
      cadherin. When adenovirus-transduced cultured keratinocytes expressing exogenous
      mouse desmoglein 1 or desmoglein 3 were incubated with exfoliative toxin B,
      desmoglein 1, but not desmoglein 3, was cleaved. Furthermore, cell surface
      staining of desmoglein 1, but not that of desmoglein 3, was abolished when
      cryosections of normal human skin were incubated with exfoliative toxin B,
      suggesting that living cells were not necessary for exfoliative toxin B cleavage
      of desmoglein 1. Finally, in vitro incubation of the recombinant extracellular
      domains of desmoglein 1 and desmoglein 3 with exfoliative toxin B demonstrated
      that both mouse and human desmoglein 1, but not desmoglein 3, were directly
      cleaved by exfoliative toxin B in a dose-dependent fashion. These findings
      demonstrate that exfoliative toxin A and exfoliative toxin B cause blister
      formation in staphylococcal scalded skin syndrome and bullous impetigo by
      identical molecular pathophysiologic mechanisms.

PMID- 11982764
TI  - Gas chromatography-mass spectrometry and molecular genetic studies in families
      with the Conradi-Hunermann-Happle syndrome.
AB  - The Conradi-Hunermann-Happle syndrome is an X-linked dominant disease that is due
      to mutations in the gene for emopamil binding protein. Emopamil binding protein
      is a Delta8-Delta7 sterol isomerase and plays a pivotal role in the final steps
      of cholesterol biosynthesis. We wanted to know to what extent this X-linked
      dominant enzyme defect has functional consequences at the biochemical level and
      whether it is possible to predict the clinical phenotype from serum sterol
      measurements. Therefore we performed sterol biochemical studies in 11 Conradi
      Hunermann-Happle syndrome families and compared the results obtained to the
      clinical and molecular genetic findings. To assess disease severity a score
      considering bone and skin involvement and further features was used. For
      evaluation of the functional consequences we studied serum samples using gas
      chromatography-mass spectrometry analysis. For mutation screening we analyzed the
      emopamil binding protein gene using polymerase chain reaction, heteroduplex
      analysis of all exons, direct sequencing, and restriction enzyme analysis.
      Mutations in the emopamil binding protein gene were found in all 11 families
      including seven novel mutations affecting exons 2, 4, and 5. Gas chromatography
      mass spectrometry analysis revealed markedly elevated levels of 8
      dehydrocholesterol and of cholest-8(9)-en-3beta-ol and helped to identify somatic
      mosaicism in a clinically unaffected man. The extent of the metabolic alterations
      in the serum, however, do not allow prediction of the clinical phenotype, nor the
      genotype. This lack of correlation may be due to differences in X-inactivation
      between different tissues of the same patient and/or loss of the mutant clone by
      outgrowth of proficient clones after some time.

PMID- 11982765
TI  - Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast
      like cell type that overexpresses Ptch.
AB  - In this study we report on the isolation and characterization of a nonepithelial,
      nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a
      patient. The BCC1 cells share many characteristics with dermal fibroblasts, such
      as the expression of vimentin, lack of expression of cytokeratins, and
      insensitivity to agents that cause growth inhibition and differentiation of
      epithelial cells; however, significant differences between BCC1 cells and
      fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA
      synthesis in response to interferon-gamma, whereas dermal fibroblasts are not.
      More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch
      and ptch2. These data indicate that basal cell carcinomas are associated with a
      functionally distinct population of fibroblast-like cells that overexpress known
      tumor-specific markers (ptch and ptch2).

PMID- 11982766
TI  - An ex vivo assay to assess the potential of skin keratinocytes for wound
      epithelialization.
AB  - Wound closure following injury to the skin is a complex process involving both
      dermal contraction and keratinocyte migration. Murine models of wound healing are
      potentially useful because of the ability to determine protein function through
      gene manipulation. Owing to the dominant role of dermal contraction, the
      technical difficulties in preparing the wound site for morphologic studies, and
      the postnatal phenotypes altering the properties of transgenic skin, there are
      difficulties in assessing the epithelial contribution to wound closure in mouse
      skin. We describe a simple ex vivo assay utilizing explant culture that enables a
      quantitative assessment of the potential of mouse keratinocytes for wound
      epithelialization. In this assay, the behavior and properties of skin
      keratinocytes mimic well those that occur at the edge of skin wounds in situ,
      including a dependence upon connective tissue element(s), proliferation, and
      migration. The epithelial cell outgrowths emerging from skin explants can be
      studied in real-time or examined at specific time-points for markers of interest
      in the epithelialization process. The assay is quantitative and can successfully
      detect increases or decreases in epithelialization potential, and can be useful
      in the characterization of transgenic mouse models.

PMID- 11982767
TI  - Transepidermal water loss does not correlate with skin barrier function in vitro.
AB  - The purpose of this study was to investigate the relationship between
      transepidermal water loss and skin permeability to tritiated water (3H2O) and the
      lipophilic penetrant sulfur mustard in vitro. No correlation was found between
      basal transepidermal water loss rates and the permeability of human epidermal
      membranes to 3H2O (p = 0.72) or sulfur mustard (p = 0.74). Similarly, there was
      no correlation between transepidermal water loss rates and the 3H2O permeability
      of full-thickness pig skin (p = 0.68). There was no correlation between
      transepidermal water loss rate and 3H2O permeability following up to 15 tape
      strips (p = 0.64) or up to four needle-stick punctures (p = 0.13). These data
      indicate that transepidermal water loss cannot be unconditionally ascribed to be
      a measure of skin barrier function. It is clear that further work should be
      conducted to interpret the significance of measuring transepidermal water loss by
      evaporimetry.

PMID- 11982768
TI  - Multiple cutaneous and uterine leiomyomas: refinement of the genetic locus for
      multiple cutaneous and uterine leiomyomas on chromosome 1q42.3-43.
AB  - Cutaneous leiomyomas, rare benign tumors originating from the arrector pili
      muscle of the hair follicle, can be associated with the common uterine fibroids
      in a syndrome called multiple cutaneous and uterine leiomyomas. Multiple
      cutaneous and uterine leiomyomas are inherited as an autosomal dominant trait,
      providing an excellent opportunity for the study of the common non-Mendelian
      manifestation of isolated uterine fibroids. This study reports the clinical and
      molecular characterization of an extended family with multiple cutaneous and
      uterine leiomyomas. Linkage analysis has shown that the disease in this family is
      linked to the recently reported genetic locus for multiple cutaneous and uterine
      leiomyomas, with a maximum two-point LOD score of 4.453 for markers D1S2670,
      D1S2785, D1S547, and D1S1609. The identification of key recombination events has
      allowed us to refine substantially the location of the genetic locus for multiple
      cutaneous and uterine leiomyomas, from 14 cM to an interval of 4.55 or 7.19 cM,
      depending on the final phenotype of a young family member in which one of the key
      recombination events has occurred. In addition, we provide a description of the
      interesting pattern and progression of the skin phenotype in this four-generation
      kindred. The refinement of the genetic locus for multiple cutaneous and uterine
      leiomyomas and the availability of an extended multigeneration pedigree will
      facilitate the identification of the mutated gene responsible for multiple
      cutaneous and uterine leiomyomas, which, in turn, may provide key information for
      the understanding of the molecular basis of the common uterine fibroids.

PMID- 11982769
TI  - Evidence for pseudodominant inheritance of atrichia with papular lesions.
AB  - Atrichia with papular lesions is a rare form of total alopecia, in which
      mutations in the hairless gene have been shown to underlie the phenotype. In the
      literature to date, atrichia with papular lesions has generally been reported to
      be inherited in an autosomal recessive manner. A few rare cases exist, however,
      in which parent-to-child transmission of atrichia with papular lesions has been
      documented. In this study, further investigations were carried out into the
      molecular basis of atrichia with papular lesions in a family with mother-to-son
      transmission by searching for mutations in the human hairless gene. Specific
      ally, we wanted to determine whether this case truly represented an example of
      dominantly inherited atrichia with papular lesions, or whether another mode of
      inheritance might be responsible for the disorder in this kindred. Pseudodominant
      inheritance, for example, occurs when an individual with a known recessive
      disorder has a clinically unaffected partner, but then unexpectedly gives birth
      to children who are affected with the same recessive disorder as the affected
      parent, and can easily be distinguished from classical dominant inheritance with
      molecular diagnosis and haplotype analysis. In the family reported here, we have
      determined that both the mother and son are, in fact, homozygous for a novel
      mutation in the hairless gene, R33X. We provide the first evidence for
      pseudodominant inheritance in atrichia with papular lesions, and at the same time
      extend our knowledge of pathogenetic mutations in the human hairless gene.
      Importantly, this information allows revisions in genetic counseling for risk of
      transmission for individuals in the family, previously impossible in the absence
      of knowing the genetic basis of atrichia with papular lesions in this unusual
      kindred.

PMID- 11982770
TI  - Clinical and molecular diagnostic criteria of congenital atrichia with papular
      lesions.
AB  - Congenital atrichia with papular lesions is a rare, autosomal recessive form of
      total alopecia and mutations in the hairless (hr) gene have been implicated in
      this disorder. Published estimates of the prevalence of this disorder remain
      surprisingly low considering pathogenetic mutations in hr have been found in
      distinct populations around the world. Therefore, it is likely that congenital
      atrichia with papular lesions is more common than previously thought and is often
      mistaken for the putative autoimmune form of alopecia universalis. To clarify
      this discrepancy, we propose criteria for the clinical diagnosis of congenital
      atrichia with papular lesions. Among these is the novel report of the consistent
      observation of hypopigmented whitish streaks on the scalp surface of affected
      individuals. Additionally, we report the identification of a novel missense
      mutation in hr from a family of Arab Palestinian origin that exhibits the
      pathognomonic features of atrichia with papular lesions. Collectively, we
      anticipate that an increased recognition of this disorder will result in more
      accurate diagnosis and the sparing of unnecessarily treatment to patients.

PMID- 11982771
TI  - Activation of epidermal growth factor receptor/ERK signaling correlates with
      suppressed differentiation in malignant acanthosis nigricans.

PMID- 11982772
TI  - Correlation analysis of production and photoisomerization of epidermal urocanic
      acid versus induction and repair of DNA photoproducts in the human skin in situ.

PMID- 11982773
TI  - Similar serum levels of soluble forms of fas and fas ligand in cutaneous T cell
      lymphoma and benign lymphocyte-mediated dermatoses: relevancy for defective
      apoptosis hypothesis.

PMID- 11982774
TI  - Does the single gel phase exist in stratum corneum?

PMID- 11982778
TI  - Nursing leadership: the time has come to just do it.

PMID- 11982779
TI  - Relationship between organizational climate and empowerment of nurses in Hong
      Kong.
AB  - AIMS: The authors explore the relationship between organizational climate and
      empowerment among the nursing staff of a regional hospital in Hong Kong. The main
      purpose of the study was to apply the modified Spreitzer measure of empowerment
      in a hospital and to examine the relationship of organizational climate to
      perceptions of empowerment. METHODS: From 658 questionnaires sent out, 331 nurses
      participated in the study with a response rate of 50.3%. Survey measures
      administered included the modified Litwin and Stringer Organizational Climate
      Questionnaire (LSOCQ) and the modified Spreitzer empowerment instrument. The
      relationships between organizational climate and empowerment were examined in a
      series of bivariate correlational analyses. The final section of the
      questionnaire asked the respondents to list three elements in the organizational
      climate that they perceived would further increase their feelings of empowerment.
      FINDINGS: Exploratory factor analysis of the modified LSOCQ resulted in six
      factors: leadership, working harmony, challenge, recognition, teamwork and
      decision making. There was a positive correlation between organizational climate
      and psychological empowerment. Using multiple regression analysis, all the six
      derived climate factors significantly accounted for 44% of the variance. Among
      the six predicting factors, leadership and teamwork showed the most positive
      relationship with psychological empowerment. Responses from the open questions on
      perception of organizational climate that further enhance nurses' feelings of
      empowerment were categorized into eight areas. They include leadership,
      communication, working relationship, recognition, structure, training, teamwork
      and stress management. CONCLUSION: The study echoes previous studies in finding
      that organizational climate and, in particular, supportive leadership and
      teamwork are related to empowerment. The findings also suggest that the nurses in
      the study did not put much emphasis on the importance of participative decision
      making.

PMID- 11982780
TI  - Achieving clinical excellence through evidence-based practice: report of an
      educational initiative.
AB  - We live in a political and professional climate which requires us to define,
      maintain and seek to improve the quality of all aspects of health care practice,
      not least via underpinning decisions and actions with robust evidence. In order
      to meet this challenge, staff must be clinically competent, reflective about
      their practice, committed to delivering a 'First Class Service' and able to work
      in a truly multidisciplinary way (as opposed to the unidisciplinary model
      frequently seen in operation). In addition, they need to be research 'literate'
      and able to contribute positively to the management and sustainment of planned
      change. For managers, the role of staff development in order to meet these goals
      is not inconsiderable. This paper discusses the process and outcomes of a
      successful educational initiative which sought to meet the plethora of challenges
      that face managers and their staff in the course of trying to achieve these
      goals.

PMID- 11982781
TI  - Evidence-based management: a literature review.
AB  - This paper presents a review of evidence-based management (EBM), exploring
      whether management activities within healthcare have been, or can be, subject to
      the same scientific framework as clinical practice. The evidence-based approach
      was initially examined, noting the hierarchy of evidence ranging from randomized
      control trials to clinical anecdote. The literature varied in its degree of
      criticism of this approach; the most common concern referring to the assumed
      superiority of positivism. However, evidence-based practice was generally
      accepted as the best way forward. Stewart (1998) offered the only detailed
      exposition of EBM, outlining a necessary 'attitude of mind' both for EBM and for
      the creation of a research culture. However, the term 'clinical effectiveness'
      emerged as a possible replacement buzz-word for EBM (McClarey 1998). The term
      appears to encompass the sentiments of the evidence-based approach, but with a
      concomitant concern for economic factors. In this paper the author has examined
      the divide between those who viewed EBM as an activity for managers to make their
      own practice accountable and those who believed it to be a facilitative practice
      to help clinicians with evidence-based practice. Most papers acknowledged the
      limited research base for management activities within the health service and
      offered some explanation such as government policy constraints and lack of time.
      Nevertheless, the overall emphasis is that ideally there should be a management
      culture firmly based in evidence.

PMID- 11982782
TI  - The development of a time-based nursing information system in dermatology
      outpatients and day therapy areas.
AB  - Over the past 10 years the provision of dermatology services in Nottingham has
      moved away from inpatient care and towards nurse-led day therapy and outpatient
      care. The current nursing information system supplies nursing activity data for
      management information and is a ward-based patient dependency classification
      system. Recently, it became apparent that nursing activity in day therapy and
      outpatients was being measured with a tool that was not designed for the purpose
      and managers were using professional judgement to aid their decisions. An
      evaluative internal consultancy was conducted to investigate the situation and
      provide recommendations for the development of an appropriate system that would
      supply more accurate information for non-ward areas. The report recommended a
      'time-based' system that avoided the fundamental philosophical mismatch between a
      reductionist, task-orientated system and the reality of holistic nursing care.
      The new system was developed on a departmental personal computer using Microsoft
      Excel spreadsheets. The full co-operation and input of the nursing staff was an
      essential ingredient in its success. The original consultancy concentrated on the
      day therapy unit but the time-based system was developed to include all
      dermatology non-ward areas.

PMID- 11982783
TI  - Latex glove disorders: a management strategy for reducing skin sensitivity.
AB  - The use of latex gloves by health care workers has increased over recent years.
      Proteins within the latex gloves and chemical additives during the manufacturing
      process have been linked to allergic skin and systemic disorders. Evidence
      suggests that latex-related skin disorders are increasing. Unless more stringent
      measures to control prolonged contact with latex gloves are implemented, skin
      disorders will continue to increase. While employees have a professional
      responsibility to reduce longer contact with latex gloves and use other safer
      alternatives, employers may also contribute through better education provisions,
      more strict monitoring and control of glove usage and purchasing gloves that are
      safer. An Infection Control Nurse can support both employees and management by
      developing and supporting better education and guidance for glove usage and an
      Employee Health Nurse could provide better care and support to affected workers.
      Glove manufacturers should identify the level of each protein in their gloves,
      the health risks involved and undertake new research to produce more
      hypoallergenic gloves. Collaborative efforts among employees, employers,
      researchers and glove manufacturers are needed to prevent the spiraling latex
      health risks to health care workers getting worse.

PMID- 11982784
TI  - Supporting organizational learning: a comparative approach to evaluation in
      action research.
AB  - For well over a decade, the organizational context of nursing in the United
      Kingdom has been one of change and reform with a policy shift towards primary and
      community led health care. Such a major shift in policy provides nurses with an
      opportunity to re-think their approaches towards the individuals and communities
      they serve in order to promote self-care, recognize achievable health goals and
      provide family and community support. Although there is a growing appreciation of
      action research as an useful approach to this kind of development, it can be
      difficult to evaluate published studies because of the diverse nature of the
      literature. This paper will present and evaluate two case studies using a
      particular conceptual device (The Normative Information Model-based Systems
      Analysis and Design) in order to explore a possible alternative to the
      interpretative narrative or positivistic hypothesis-testing models used to report
      other kinds of nursing research and enlarge the debate about process evaluation.

PMID- 11982785
TI  - Developing scholarship in nursing - steps within a strategy.
AB  - This paper seeks to share with the reader some of the mechanisms currently being
      used to generate scholarship in academic nursing, both at the institutional and
      individual levels. It then goes on to explore other ways in which educational
      managers might encourage scholarly activity. Finally, it presents the
      crystallization of ideas generated during discussions conducted with lecturers
      focusing on their selection of a workable path towards a future of scholarship,
      for them as an academic. It is intended as food for thought for managers of
      educational programmes and individual nurse academics as they scan the horizons
      of the future in an attempt to make the 'best' decisions for the profession of
      nursing and individuals within it.

PMID- 11982786
TI  - New UKCC report sets out way forward on regulating a higher level of practice.

PMID- 11982788
TI  - Phototransduction for human melatonin suppression.
AB  - Human adult males were exposed to combinations of two illuminances and two
      broadband spectral power distributions over the course of four night-time
      sessions. Results showed that melatonin suppression is dominated by short visible
      wavelengths (420-520 nm), consistent with recently published studies. Although
      the authors of these recent studies suggest that a novel opsin underlies
      melatonin suppression, the present paper offers a more conservative
      interpretation of the data based on what is known about existing photoreceptors
      and associated neuroanatomy and neurophysiology.

PMID- 11982789
TI  - Daily variation in the concentration of 5-methoxytryptophol and melatonin in the
      duck pineal gland and plasma.
AB  - The duck pineal gland rhythmically produces two 5-methoxyindole compounds, i.e. 5
      methoxytryptophol and melatonin. 5-Methoxytryptophol levels are low at night and
      high during the day, while melatonin concentrations are high at night and low
      during the day. The melatonin rhythm reflects oscillations in the activity of
      serotonin N-acetyltransferase (AA-NAT; a penultimate and key regulatory enzyme in
      the melatonin biosynthetic pathway). The activity of hydroxyindole-O
      methyltransferase (HIOMT; an enzyme involved in the synthesis of both 5
      methoxytryptophol and melatonin) does not exhibit any significant rhythmic
      changes throughout the 24-hr period. Plasma levels of melatonin exhibited daily
      changes that were parallel to fluctuations in pineal melatonin content. Although
      plasma concentrations of 5-methoxytryptophol were low in ducks, they showed daily
      variations. The mean 5-methoxytryptophol concentration between zeitgeber time 9
      (ZT9) and ZT15 was 2.4-times higher than the mean value for samples collected
      between ZT18 and ZT3. These findings indicate that in the duck the pineal
      production of 5-methoxytryptophol and melatonin may be inversely correlated.

PMID- 11982790
TI  - How important is stimulation of alpha-adrenoceptors for melatonin production in
      rat pineal glands?
AB  - The objective of this study was to determine the role of alpha-adrenoceptors in
      melatonin production by rat pineal gland. Pineal glands were isolated from adult
      male rats and maintained in organ baths. The perfusate was sampled every 5 min,
      stored, and later assayed for melatonin. Exposure to norepinephrine (10 microM)
      or the beta-adrenoceptor agonist orciprenaline (2-10 microM) increased the
      glands' production of melatonin. The time courses of melatonin production in
      response to these agonists were unaffected by the rats' pretreatment in vivo with
      the alpha-adrenoceptor antagonist prazosin (2 mg/kg i.p., three times). Rats that
      had had their superior cervical ganglia removed were primed with either
      orciprenaline (2 mg/kg i.p) or both orciprenaline and phenylephrine (1 mg/kg i.p)
      1 hr before decapitation. Exposure of the pineal glands from these rats to
      orciprenaline evoked melatonin release that was similar in each group. These
      results lend weight to the suggestion that the marked potentiation by alpha
      adrenoceptor agonists of the stimulation of cAMP and N-acetyltransferase (NAT) by
      beta-adrenoceptor agonists, demonstrated most readily in cultured glands or
      dispersed rat pinealocytes, does not carry over into significant augmentation of
      melatonin production in intact pineal glands.

PMID- 11982791
TI  - Comparative analysis of the protective effects of melatonin and vitamin E on
      streptozocin-induced diabetes mellitus.
AB  - There is a clearly documented link between diabetic complications and lipid
      peroxidation. Hyperglycemia causes a reduction in levels of protective endogenous
      antioxidants and increases generation of free radicals. The present study was
      carried out to compare the protective effects of melatonin and vitamin E against
      streptozocin (STZ)-induced diabetes in rats. Melatonin was administered s.c. (100
      microg/kg) whereas vitamin E was given i.p. (100 mg/kg) after induction of
      diabetes with STZ (60 mg/kg). Plasma total cholesterol, triglyceride and low
      density lipoprotein (LDL) levels were increased in STZ group while both melatonin
      and vitamin E injection caused a significant decrease in the levels of all these
      parameters. The lipid lowering effect of melatonin was greater than that of
      vitamin E. Melatonin caused a significant decrease in brain, liver and kidney
      tissue malondialdehyde (MDA) levels which were increased because of STZ-induced
      diabetes. Vitamin E also reduced elevated MDA concentrations in diabetic rat
      tissues, but the effect of melatonin was more potent than that of vitamin E.
      Furthermore, treatment of diabetic rats with melatonin increased brain and kidney
      glutathione peroxidase (GSH-Px) activity to the levels below that of control
      rats. Vitamin E was found to be less effective on GSH-Px activity levels in brain
      and kidney than melatonin whereas it was more potent than melatonin in liver. In
      summary, melatonin prevents many diabetic complications by reducing oxidative
      stress and protects organisms from oxidative damage and dyslipidemia. Considering
      the much lower molar concentration of melatonin compared with vitamin E,
      melatonin seems to be a more potent antioxidant, especially in the brain and
      kidney.

PMID- 11982792
TI  - Melatonin protects against gentamicin-induced nephrotoxicity in rats.
AB  - Acute renal failure is a major complication of gentamicin (GEN), which is widely
      used in the treatment of gram-negative infections. A large body of in vitro and
      in vivo evidence indicates that reactive oxygen metabolites (or free radicals)
      are important mediators of gentamicin nephrotoxicity. In this study we
      investigated the role of free radicals in gentamicin-induced nephrotoxicity and
      whether melatonin, a potent antioxidant could prevent it. For this purpose female
      Sprague-Dawley rats were given intraperitoneally either gentamicin sulphate (40
      mg/kg), melatonin (10 mg/kg), gentamicin plus melatonin or vehicle (control)
      twice daily for 14 days. The rats were decapitated on the 15th day and kidneys
      were removed. Blood urea nitrogen (BUN) and creatinine levels were measured in
      the blood and malondialdehyde (MDA) and glutathione (GSH) levels, protein
      oxidation (PO) and myeloperoxidase (MPO) activity were determined in the renal
      tissue. Gentamicin was observed to cause a severe nephrotoxicity which was
      evidenced by an elevation of BUN and creatinine levels. The significant decrease
      in GSH and increases in MDA levels, PO and MPO activity indicated that GEN
      induced tissue injury was mediated through oxidative reactions. On the other hand
      simultaneous melatonin administration protected kidney tissue against the
      oxidative damage and the nephrotoxic effect caused by GEN treatment.

PMID- 11982793
TI  - Melatonin protects against copper-mediated free radical damage.
AB  - Copper is an essential trace element which forms an integral component of many
      enzymes. While trace amounts of copper are needed to sustain life, excess copper
      is extremely toxic. Copper has been implicated in various neurodegenerative
      disorders, such as Wilson's and Alzheimer's diseases. Previous studies showed
      that melatonin, the principle secretory product of the pineal gland, binds Cupric
      chloride (Cu2+) and that this may have implications in copper-induced
      neurodegenerative diseases. In the present study, in vitro copper-mediated lipid
      peroxidation was induced. Melatonin (5 mM) protected against copper-mediated
      lipid peroxidation in liver homogenates. Electron micrographs of in vivo
      administered Cu2+ and melatonin show that melatonin affords some protection to
      rat hepatocytes in the presence of copper. Electrochemical studies performed show
      that melatonin, in addition to binding Cu2+, may provide protection against
      copper-mediated free radical damage by binding Cu1+. The findings of these
      studies provide further evidence for the neuroprotective role of melatonin.

PMID- 11982794
TI  - 2[125I]Iodomelatonin binding and interaction with beta-adrenergic signaling in
      chick heart/coronary artery physiology.
AB  - 2[125I]Iodomelatonin ([125I]Mel) binding sites were characterized on membrane
      preparations of young chick hearts. [125I]Mel binding was rapid, saturable,
      stable, reversible, specific and of picomolar affinity and femtomolar density.
      Guanosine 5'-O-(3-thiotriphosphate) significantly lowered the binding affinity by
      one- to twofold, supporting G-protein linkage of melatonin receptors. Binding was
      detected as early as embryonic day-9 (E9), and increased steadily peaking at E13
      before it slowly declined to about 15% of the peak level a week posthatch.
      Specific [125I]Mel binding was significantly increased by in ovo administration
      of inotropic agents dopamine and isoproterenol. Melatonin or 2-iodo-N-butanoyl
      tryptamine inhibited isoproterenol-stimulated cAMP accumulation in primary heart
      cell cultures and the effect was attenuated after pretreatment with pertussis
      toxin (PTX). Localization of melatonin receptors using autoradiography showed
      intense labeling in the coronary arteries in all age groups whereas those in the
      myoblasts decreased as the heart matured. While the myoblasts and
      undifferentiated developing coronary arteries expressed melatonin MT1 receptor
      subtype in E11 hearts as detected by immunostaining with anti-MT1 receptor serum,
      immunoreactivities were observed mostly on the endothelium/subendothelium and
      smooth muscle cells of the well developed coronary vessels in posthatch hearts.
      Collectively, our data suggest the presence of PTX-sensitive, G protein-coupled
      melatonin receptors, whose expression is up-regulated by dopamine and
      isoproterenol, in the chick heart. Activation of these receptors, which include
      MT1 subtype, may modulate beta-adrenergic receptor-mediated cAMP signaling in the
      control of chick heart and coronary artery physiology.

PMID- 11982795
TI  - Evaluation of plasma levels of melatonin after midazolam or sodium thiopental
      anesthesia in children.
AB  - Midazolam and sodium thiopental are two commonly used drugs in anesthesia for
      minor surgical procedures in children. A relationship exists between
      benzodiazepines (BNZ), barbiturates and melatonin. Whereas these drugs increase
      pineal melatonin production, the indoleamine amplifies the effects of both BNZ
      and barbiturates on the central nervous system (CNS). Our purpose was thus to
      analyze the plasma levels of melatonin before and during midazolam or sodium
      thiopental anesthesia in children subjected to ambulatory surgical procedures.
      Midazolam (0.4 mg/kg) or sodium thiopental (5 mg/kg) were administered i.v. to 33
      and 32 children (aged between 2 and 14 yr), respectively, and blood samples were
      taken before and 5, 10 and 20 min after the drugs were administered. Melatonin
      was measured in plasma by a commercial radioimmunoassay kit previously
      standardized in our laboratory. The results showed that neither midazolam nor
      sodium thiopental anesthesia significantly affected the levels of melatonin
      studied at anytime. Significant correlations were found comparing the levels of
      melatonin between the different times studied. These results suggest that
      midazolam or sodium thiopental did not affect melatonin production by the pineal
      gland, thus avoiding a possible potentiating effect of the indoleamine on the
      central effects of these drugs during anesthesia. However, the possibility that
      changes in melatonin had been masked by the antioxidant role of the neurohormone
      are discussed.

PMID- 11982796
TI  - The identification of the UV degradants of melatonin and their ability to
      scavenge free radicals.
AB  - Ultraviolet (UV) light is known to induce the generation of free radicals in
      biological tissues such as skin. Of these free radicals, the O2-. and
      particularly the.OH radical can induce cellular damage including lipid
      peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV
      irradiation has received much attention recently. One such antioxidant, which has
      the potential to be incorporated into sunscreens, is the pineal secretory product
      melatonin. One of the concerns of using melatonin in sunscreens is its
      photostability. In the present study, we investigated the photostability of
      melatonin subjected to UV irradiation. In addition, we used liquid chromatography
      mass spectrometry (LC-MS) to identify the degradants and we also assessed the
      ability of the degradants to inhibit O2-. generation as well as lipid
      peroxidation in rat brain homogenate. The results show that UV irradiation of
      melatonin (0.1 mg/mL) using a 400-W lamp for 2 hr caused a significant decline of
      melatonin to 18% of its original concentration after 20 min, with the decline
      continuing until the melatonin concentration reaches zero at 120 min. The LC-MS
      results show that the degradants of melatonin are 6-hydroxymelatonin and N1
      acetyl-N2-formyl-5-methoxykynurenamine (AFMK). These degradants were able to
      provide equipotent activity against potassium cyanide (KCN)-induced superoxide
      generation compared to non-irradiated melatonin. Thus, the study shows that
      although melatonin is rapidly degraded by UV irradiation, the degradants retain
      antioxidant activity, making melatonin a likely candidate for inclusion in
      sunscreens.

PMID- 11982797
TI  - Melatonin attenuates MPP+-induced neurodegeneration and glutathione impairment in
      the nigrostriatal dopaminergic pathway.
AB  - In this study we selected a rat model of Parkinson's disease (PD) by using
      intrastriatal infusion of the 1-methyl-4-phenyl-pyridinium ion (MPP+) to
      investigate the neuroprotective action of melatonin and its inhibitory activity
      on MPP+-impaired glutathione (GSH) system in the nigrostriatal system. Results
      show that MPP+ caused not only a severe neuronal injury in the striatum and in
      the ipsilateral substantia nigra (SN), but it also induced a significant decrease
      in GSH levels and an increase in the GSSG/GSH ratio 3 days after intrastriatal
      MPP+ infusion. Intraperitoneal co-administration of melatonin (10 mg/kg, five
      times) significantly attenuated MPP+-induced nigrostriatal neurotoxicity and GSH
      impairment. Depletion of cytosolic GSH by L-buthionine sulfoximine (BSO) did not
      cause neuronal damage by itself. It, however, when co-administrated with MPP+,
      potentiated the GSH reduction in the striatum, without aggravating nigrostriatal
      neurodegeneration induced by MPP+. Moreover, the MPP+-caused neuronal damage was
      positively correlated with a rising ratio of GSSG/GSH, but not with a drop of
      GSH. These results suggest that the MPP+-triggered oxidative stress may play a
      more important role than the loss of the antioxidant GSH in determining neuronal
      injury. Interestingly, the neuronal damage and oxidative stress elicited by co
      treatment of BSO with MPP+ were effectively reduced by melatonin. Our results
      hence provide direct evidence showing that melatonin attenuates MPP+-induced
      nigrostriatal dopaminergic injury by its ability to impede the increase of
      GSSG/GSH ratio; therefore melatonin may have therapeutic implications in PD.

PMID- 11982798
TI  - Melatonin induces alterations in protein expression in the Xenopus laevis retina.
AB  - The hormone melatonin is synthesized by pinealocytes and retinal photoreceptors
      with a diurnal rhythm. Melatonin produced in the retina at night is thought to
      exert local modulatory effects by binding to specific receptors in several
      different retinal cell types. The mechanisms by which melatonin influences
      circadian activity in retinal cells is poorly understood. Suppression of cyclic
      AMP synthesis appears to be a major signaling pathway in response to melatonin
      receptor binding in many tissues. A potential downstream consequence of melatonin
      induced changes in cyclic AMP concentrations and protein phosphorylation is the
      up- or down-regulation of expression of specific genes. In this report, we
      examined the changes in expression levels of specific proteins in the neural
      retina and retinal pigment epithelium (RPE) in response to melatonin treatment,
      because both of these tissues express melatonin receptors. Neural retina and RPE
      isolated from the eyes of Xenopus laevis were treated with or without 1 microM
      melatonin for 6 hr, then the rapidly synthesized tissue proteins were
      radiolabeled by a 15 min incubation with 35S-methionine, and the proteins were
      subsequently analyzed by two-dimensional gel electrophoresis and autoradiography.
      In both the neural retina and RPE, the densities of some specific proteins were
      altered in response to melatonin treatment, and the few protein spots that were
      altered were distinct between the two tissues. These results support the concept
      that one function of melatonin may be to regulate the expression of specific
      genes and the consequent protein levels, and that the target genes may differ
      according to the cell or tissue type.

PMID- 11982799
TI  - Head and abdominal melatonin of summer and winter bees.

PMID- 11982804
TI  - New Insights in End-Stage Renal Disease. Proceedings of the 1st International
      Congress. Madrid, Spain, November 18-20, 2001.

PMID- 11982800
TI  - Melatonin triggers Crohn's disease symptoms.

PMID- 11982805
TI  - Strategies to decrease cardiovascular mortality in patients with end-stage renal
      disease.

PMID- 11982806
TI  - Measurement of renal function in pre-ESRD patients.
AB  - The measurement of renal function in pre-dialysis patients is important in order
      to determine the appropriate time to begin renal replacement therapy, to forecast
      the start, and to compare, in groups of patients, the efficiency of different
      treatments that limit renal disease progression. The most reliable methods, such
      as inulin clearance or measurement by radioisotopes, are too awkward for the
      usual clinical follow-up of patients. Although much simpler and almost as
      reliable, the use of iohexol radiologic contrast does not allow the frequent
      monitoring of the patient either. The determinations of the plasmatic creatinine
      and its clearance or the estimate of the glomerular filtration rate by means of
      equations derived from the creatinine are the methods most often used in order to
      measure renal function, although not without problems in pre-dialysis. In order
      to try to overcome such problems, more precise equations and procedures,
      including the measurement of averaged urea-creatinine clearance or creatinine
      clearance with cimetidine, have been designed that better estimate the glomerular
      filtration rate. However, none of these methods is totally reliable in pre
      dialysis. A new endogen marker, cystatin C, has advantages over creatinine,
      though more studies are needed in pre-dialysis in order to ascertain its use. The
      initial proposal of the National Kidney Foundation's Kidney Disease Outcome
      Quality Initiative (DOQI) guidelines to use weekly Kt/V and nutritional
      parameters to determine the time for starting renal replacement therapy has
      widened the prospects of the debate on the measurement of renal function in pre
      dialysis, but further work is required to define their role in pre-dialysis
      patients' follow-up.

PMID- 11982807
TI  - Slowing the progression of renal failure.
AB  - In recent years several multicentric prospective studies have demonstrated the
      efficacy of some therapeutic measures to slow the progression of renal diseases.
      Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and
      angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic
      alternative: The antiproteinuric effect of these drugs is an excellent surrogate
      marker and a predictor of the beneficial influences on the progression of renal
      failure. The type of renal disease, an inadequate control of blood pressure, and
      the presence of obesity may counteract the beneficial influences of RAS
      inhibition, whereas early treatment of all patients with significant proteinuria
      before the appearance of renal insufficiency and combined therapy with an ACEI
      and an ARA may augment it. Dietary protein restriction is a classic treatment of
      chronic renal insufficiency whose effectiveness has been validated by
      multicentric studies. However, a poor compliance of the patient and the risk of
      malnutrition with very strict protein restriction could limit the benefits of
      this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of
      smoking, and regular physical exercise are interventions whose therapeutic
      potential is progressively recognized, particularly in type 2 diabetic
      nephropathy. Early correction of anemia may contribute to the slowing of renal
      disease progression. Although further studies are required, the accumulated
      evidence and the likelihood of additive beneficial effect of these therapeutic
      measures advise their combined implementation in patients with chronic renal
      diseases.

PMID- 11982808
TI  - New approaches to delay the progression of chronic renal failure.
AB  - BACKGROUND: The molecular cloning of many bone morphogenetic proteins (BMP)
      encoding genes and their identification as transforming growth factor-beta (TGF
      beta) relatives enhanced the interest in these molecules and allowed expression
      and functional studies to be performed. METHODS: Rats with ureteral obstruction
      were distributed into four groups. Group 1 received vehicle, group 2 received
      enalapril 12.5 mg/kg body wt/day, group 3 received 50 or 300 microg/kg body wt
      BMP-7, and group 4 received both enalapril and the high dose of BMP-7. We also
      studied the effects of BMP-7 administration in a model streptozocin-induced
      diabetes. RESULTS: Treatment with BMP-7 in rats with ureteral obstruction of 3
      days duration and subsequent release indicated that this compound decreases
      interstitial volume and accelerates the return of renal function. After 16 weeks
      of diabetes, the rats were treated with BMP-7. The administration of BMP-7
      partially reversed renal hypertrophy, restored GFR to normal, and decreased
      proteinuria. CONCLUSIONS: These studies indicate that administration of BMP-7
      maintains and restores renal function and structure in animals with ureteral
      obstruction and diabetic nephropathy.

PMID- 11982809
TI  - An update on the referral pattern of patients with end-stage renal disease.
AB  - This article first describes the epidemiology and reasons of late referal to the
      nephrologist of patients suffering from end-stage renal disease (ESRD). Depending
      on the definition, between 25 and 50% of worldwide ESRD patients are referred
      very late. Second, the relation of late referral to the quality of pre-ESRD care,
      its impact on the selection of dialysis modality, on the time of start of
      dialysis and on the use of an adequate vascular access, are discussed. Finally,
      the economic aspects of late referral are described and ways to improve the
      referral pattern are proposed.

PMID- 11982810
TI  - Anemia and left ventricular hypertrophy in chronic kidney disease populations: a
      review of the current state of knowledge.
AB  - The increasing awareness of the high prevalence of cardiovascular disease (CVD)
      in the dialysis population has led clinical nephrologists and researchers to
      focus their attention on processes and factors that are present in patients prior
      to dialysis. It is clear that many of the risk factors for kidney disease and
      cardiovascular disease are similar: This may account for the high prevalence of
      CVD within the dialysis population. However, it is evident that there are unique
      risk factors for CVD that are present in patients with chronic kidney disease
      (CKD). These unique uremia-related risk factors for CVD include anemia,
      hyperparathyroidism, abnormalities of mineral metabolism, and acidosis. Of note,
      the association of anemia, or lower levels of hemoglobin, have been consistently
      described in all populations with kidney disease. Left ventricular hypertrophy
      has long been known as an independent risk factor for death and CV events, in
      both the dialysis and general populations. There have been accumulating data that
      LVH and left ventricular (LV) growth occur prior to dialysis in patients with
      kidney disease, and that the prevalence of LVH in that group of patients is
      caused by, conventional risk factors for LVH (e.g., hypertension) as well as
      nonconventional risk factors such as anemia.

PMID- 11982811
TI  - What should the optimal target hemoglobin be?
AB  - Partial correction of anemia in patients with chronic kidney disease (CKD)
      improves anemia-related symptoms. However, controversy remains as to whether
      total correction of anemia provides benefits over and above those afforded by
      partial correction. There is some evidence showing that normalization of
      hemoglobin (Hb) concentrations may improve the cardiac hyperdynamic state in CKD
      patients and reduce the diameter of the left ventricle. Further studies have
      shown that normalization of Hb improves cognitive function and physical
      capacities as measured by quality of life (QoL) tests. Large studies have shown
      that in dialysis patients there is a close inverse relationship between
      hematocrit (Hct) levels and mortality and morbidity. Moreover, there is evidence
      suggesting that Hct levels higher than those recommended by European Best
      Practice Guidelines (EBPG) and the National Kidney Foundation Dialysis Outcome
      and Quality Initiative (NKF-DOQI provide better outcomes for patients with CKD.
      However, when Hb concentrations are increased to normal in selected patients with
      cardiac disease, congestive heart failure, or ischemic cardiopathy, higher
      mortality rates are evident. Therefore, while the majority of patients with CKD
      may experience significant benefits when Hb is normalized, it seems prudent to
      recommend individualized target Hb concentrations for each patient, taking into
      account factors such as age, sex, employment status, physical activity, and co
      morbidities.

PMID- 11982812
TI  - Influence of target hemoglobin in dialysis patients on morbidity and mortality.
AB  - Since the introduction of recombinant human erythropoietin (rHuEPO) in 1989, the
      level of anemia correction has been debated. Information developed from clinical
      trials and observational studies have given conflicting results. The normal
      hematocrit (Hct) trial of Besarab et al showed no benefit, and a possible risk,
      of correcting the Hct from 30% to 42% in hemodialysis patients with NYHA class I
      to III cardiac disease. The study of Moreno et al in non-cardiac patients showed
      improved Sickness Impact Profile and Karnofsky scores in hemodialysis patients
      when their Hct was increased from 31% to 38.5%. Hospitalizations were
      significantly reduced. Observational studies from Madore et al, Xia et al, Ma et
      al, and Collins et al all show that increased morbidity and mortality are
      significantly associated with Hct <33%. Recent data on incident hemodialysis
      patients indicate the associated risk of death was not different for patients
      with Hct 33 to <36% versus Hct 36 to <39%. Hospitalization risks and associated
      costs were significantly less in the patients with Hct 36 to <39%, suggesting
      that higher Hct values may be less of a concern than previously considered. The
      current data suggest that patents with advanced cardiac disease should avoid Hct
      values in the normal range. In others, Hcts at least up to 39% appear to be safe
      and effective. Based on this review, a reasonable target Hct range may be 33 to
      39%, which balances the risks and potential benefits.

PMID- 11982813
TI  - Occult infection of old nonfunctioning arteriovenous grafts: a novel cause of
      erythropoietin resistance and chronic inflammation in hemodialysis patients.
AB  - BACKGROUND: Occult infection of old nonfunctioning arteriovenous grafts (AVGs) is
      frequent among hemodialysis patients. It is a recognized cause of bacteremia and
      other infectious complications. Additionally, old nonfunctioning AVGs may be
      harbingers of other noninfectious complications. The aim of this study was to
      investigate whether occult infection of old nonfunctioning AVGs is a cause of a
      chronic inflammatory state in hemodialysis patients. METHODS: This study was
      performed in two phases: In the first phase (study 1), 22 patients with
      clinically proven occult infection of old nonfunctioning AVG were identified, and
      data on hemoglobin, weekly erythropoietin dose, and albumin levels were collected
      retrospectively. Comparisons were made between values obtained pre- and post-AVG
      resection. In the second phase (study 2), we examined whether the presence of a
      chronic inflammatory state is associated with occult AVG infection in old
      nonfunctioning AVGs. Twenty hemodialysis patients were identified with chronic
      inflammatory state based on erythropoietin dose (units/wk)/hematocrit ratio>470,
      serum albumin <3.3 g/dL, and CRP>25 mg/L. Among these patients, we found eight
      with old nonfunctioning AVGs. We then performed indium-labeled white blood cell
      (WBC) scans on the eight patients to screen for occult infection of old
      nonfunctioning AVGs. The AVGs with positive indium scan were resected and
      cultured. Data on hematocrit, erythropoietin dosing, serum albumin, ferritin, and
      CRP were obtained at 2 months following AVG resection and compared to pre
      resection values. RESULTS: In study 1, the 22 patients with occult infection of
      old nonfunctioning AVG exhibited profound anemia and hypoalbuminemia. Their mean
      hemoglobin was 9.2 +/- 1.2 g/dL which improved to 11.6 +/- 0.8 g/dL (P < 0.05) 3
      months after AVG resection. Their mean serum albumin was 3.3 +/- 0.5 g/dL which
      improved to 3.8 +/- 0.2 g/dL (P < 0.05) 3 months after AVG resection. Their mean
      erythropoietin dosages (units/patient/wk) fell from 14,240 +/- 350 to 6,675 +/-
      455 (P < 0.05). In study 2, among the 8 patients with chronic inflammatory state
      and old nonfunctioning AVG, 6 (75%) had positive indium scans and underwent
      surgical resection that proved bacterial infection. Upon follow-up, the 2-month
      data showed a remarkable improvement in the following parameters: weekly
      erythropoietin dose/hematocrit ratio from 622 +/- 137 to 254 +/- 28 (P < 0.05),
      plasma ferritin values from 690 +/- 126 ng/mL to 247 +/- 42 ng/mL (P < 0.01), and
      plasma CRP from 56.7 +/- 9.0 to 14.5 +/- 3.8 mg/L (P < 0.01). Serum albumin
      values also improved from 3.07 +/- 0.08 g/dL to 3.34 +/- 0.14 g/dL (P = 0.13).
      Percent plasma iron saturation did not appreciably differ from baseline (20.5% +/
      4.4% to 19.8 +/- 1.9%, P = 0.89). CONCLUSIONS: Occult infection of old
      nonfunctioning AVG is a common cause of erythropoietin resistance and chronic
      inflammatory state among hemodialysis patients. Resection of old nonfunctioning
      AVGs with occult infection is associated with resolution of markers of chronic
      inflammatory state.

PMID- 11982814
TI  - Darbepoetin alfa: a new therapeutic agent for renal anemia.
AB  - Darbepoetin alfa is a super-sialylated analog of human erythropoietin that has a
      longer circulating half-life in vivo compared to both native and recombinant
      hormone. It has the same mechanism of action as erythropoietin, stimulating the
      same surface membrane receptor and triggering the same intracellular chain of
      events. An extra two N-linked carbohydrate chains, however, gives darbepoetin
      alfa greater metabolic stability in vivo, and its terminal half-life after
      intravenous administration is approximately three times longer than for
      intravenous erythropoietin. This in turn allows injections of the drug to be
      given less frequently, and studies have shown that once-weekly and once-every
      other-week dosing can maintain the hemoglobin concentration in patients with
      renal anemia. The recommended starting dose for darbepoetin alfa is 0.45
      microg/kg once weekly for both IV and SC administration, with subsequent
      titration based on the hemoglobin concentration. The adverse event profile is
      very similar to that seen with rHuEPO, and no antibodies have been detected in
      several thousand patients exposed to the drug, some of whom have been treated for
      up to five years now. Following a clinical research program that began in
      November 1996, darbepoetin alfa was finally approved by the European Commission
      in June 201, and by the FDA in September 201.

PMID- 11982815
TI  - Kidney and hypertension.
AB  - There is a unique relationship between the kidney and blood pressure (BP): on the
      one hand, renal dysfunction and particularly renal disease cause an increase in
      BP, while on the other hand, high BP accelerates loss of function of the diseased
      kidney. Transplantation studies, both in experimental animals and humans,
      documented that "blood pressure goes with the kidney," a normotensive recipient
      of a kidney genetically programmed for hypertension (HT) will develop HT, while
      conversely hypertensive patients with renal failure receiving the kidney of a
      normotensive donor may develop normotension. Family studies showed higher BP
      values and more frequent HT in first degree relatives of patients with primary
      glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion
      that HT accelerates the loss of renal function has been proposed at the turn of
      the century, but definite evidence by observational and interventional studies
      has only been provided in the last two decades. The issue has been much
      confounded by the mistaken believe that damaged kidneys require higher BP values
      in order to function properly. The mechanisms of BP increase in renal disease
      comprise: salt retention, inappropriate activity of the renin-angiotensin system
      (RAS) and of the sympathetic nerve system as well as impaired endothelial cell
      mediated vasodilatation. There is ample evidence both in primary renal disease
      (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT,
      RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme
      inhibitors or angiotensin II type 1 receptor blockers has BP-independent
      renoprotective effects. More recently, it has also been shown that blockade of
      the sympathetic nerve system has BP-independent effects on albuminuria and on
      glomerulosclerosis.

PMID- 11982816
TI  - How should the immunosuppressive regimen be managed in patients with established
      chronic allograft failure?

PMID- 11982817
TI  - Hyperlipidemia: a risk factor for chronic allograft dysfunction.
AB  - While the early results of renal transplantation have improved in the last years,
      but the long-term allograft survival have not improved to the same extent. The
      major cause of these graft losses is chronic allograft dysfunction (CAD). The
      pathogenesis of CAD is complex and results from a interaction of immune and
      nonimmune factors. Between these non-immunological related factors there are two
      cardiovascular risk factors, hypertension and especially hyperlipidemia, that
      have been implicated in the development and progression of CAD. Lipid profile
      abnormalities are very prevalent in renal transplant patients. In last years
      several authors have reported an association between different lipid profile
      alterations and CAD. We conducted an observational study in our group to
      determine the relationship between different lipid disturbances and CAD. The
      hypertriglyceridemia and the Lp(a)>30 mg/dL before and after transplantation
      were, between the lipid abnormalities, the two independent risk factors for CAD
      in a multivarite analysis.

PMID- 11982818
TI  - Cardiovascular disease after renal transplantation.
AB  - Cardiovascular disease is a major hazard limiting the life expectancy of renal
      transplant recipients and the most frequent cause of late allograft loss.
      Patients with renal disease have usually been exposed for both traditional, and
      for them unique, risk factors over a prolonged period of time and may carry the
      burden of advanced atherosclerotic disease already at the time of
      transplantation. The observed survival benefit of transplantation is probably
      from elimination of the numerous uremia-related risk factors. However,
      immunosuppressive therapy and the chronic inflammatory state, together with
      genetic susceptibility and not infrequently impaired renal function, may bring
      about new potentially atherogenic conditions. Metabolic risk factors may
      jeopardize both patient and graft survival. Several observational studies provide
      evidence for the negative impact of preexisting metabolic abnormalities on long
      term outcomes. Identification of modifiable cardiovascular risk factors may
      enable risk reduction also in renal transplant recipients. Results of ongoing
      intervention trials are awaited. The observed improvement of patient survival
      after renal transplantation during the past decade may reflect the increasing
      awareness and more optimal care of patients throughout the course of renal
      disease.

PMID- 11982819
TI  - Return to dialysis after renal transplantation. Which would be the best way?
AB  - The exact moment to return to dialysis when a graft fails has not clearly been
      established. Furthermore, there is no agreement with respect to whether the
      guidelines accepted for patients entering dialysis for the first time are
      adequate for this subgroup of patients with advanced renal failure, due to the
      special characteristics of these patients, derived from the immunosuppressive
      medications they are taking among other accompanying factors. We reviewed a group
      of renal transplant patients who returned to dialysis and compared them with a
      group of patients entering dialysis for the first time. Patients with chronic
      renal failure due to graft failure had a poorer renal function at the time
      entering dialysis and a more profound anemia. Additionally, complications
      considered such as the number of hospital admissions during the first year after
      initiation of dialysis were considerably higher in the group of transplanted
      patients. We advocate for an earlier referral to the dialysis unit, a more
      aggressive erythropoietin therapy in the phase of advanced renal failure due to
      chronic allograft nephropathy, and in selected cases retransplantation before
      definitive graft loss.

PMID- 11982820
TI  - Cell apoptosis and hemodialysis-induced inflammation.
AB  - Hemodialysis patients exhibit a defective immune response leading to an increased
      susceptibility of infections and neoplasms. Far from being helpful, dialytic
      therapy per se also may be responsible for this acquired immunodeficiency.
      Dialysis membranes and bacterial products present in dialysis water may trigger
      and even perpetuate an abnormal mononuclear cell activation. Upon contact with
      cellulosic dialysis membranes, monocytes display an increased expression of
      surface markers of cell activation, such as adhesion molecules CD18, CD49, CD54
      and the lipopolysaccharide (LPS) ligand (CD14). Moreover, proinflammatory
      cytokines as IL-1beta and TNF-alpha are released both in vivo and in vitro when
      monocytes are exposed to cellulosic membranes. Of special interest is the fact
      that end-stage renal disease patients undergoing hemodialysis exhibit an
      increased mononuclear cell apoptosis. This apoptosis is directly related to the
      degree of biocompatibility of the dialysis membrane. Apoptosis is activated when
      monocytes enter in contact with the cellulosic dialysis membrane through cell
      surface receptors linked to G-proteins. In early steps of apoptosis signaling,
      pertussis toxin-sensitive G proteins are coupled to protein kinase C (PKC)
      dependent phosphorylative mechanisms. Furthermore, recent evidence support that
      the execution phase of apoptosis is mediated by a caspase-3 dependent pathway.
      Finally, very recent available data support that monocytes subjected to repeated
      activation suffer a process of accelerated senescence, as demonstrated by the
      senescent phenotype (CD14 and CD32) expressed and their shortened telomeric
      length. This senescent profile may generage a defective cellular response in
      acute stress situations, explaining (at least in part) the altered immune
      response observed in hemodialysis patients.

PMID- 11982821
TI  - Chronic inflammation and clinical outcome in adult hemodialysis patients.

PMID- 11982822
TI  - Inflammation and cardiovascular risk in dialysis patients.
AB  - BACKGROUND: Chronic inflammation, as evidenced by increased levels of C-reactive
      protein (CRP), predicts all-cause and cardiovascular mortality in hemodialysis
      patients in short-term studies. Whether CRP is also predictive in the long-term
      follow-up is unknown. METHODS: We conducted a 4-year follow-up of a cross
      sectional study in a cohort of 280 stable hemodialysis patients. CRP was
      determined once at the beginning of the study, and all-cause as well as
      cardiovascular mortality was monitored prospectively. RESULTS: During follow-up,
      123 patients (43.9%) had died, mostly from cardiovascular events (58.5%)
      corresponding to an annual mortality rate of 11%. Overall mortality and
      cardiovascular mortality were significantly higher in patients with a CRP more
      than 8 mg/L (73% vs. 39% and 87% vs. 55%, respectively). Multivariate Cox
      regression analysis demonstrated that age, CRP, and preexisting cardiovascular
      disease were the most powerful predictors, but the presence of diabetes, albumin,
      and BMI also remained in the model. CONCLUSION: A single determination of CRP is
      a powerful indicator of all cause and cardiovascular death even after a follow-up
      period of 4 years in patients on hemodialysis treatment.

PMID- 11982823
TI  - Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of
      interleukin-6?
AB  - There is growing evidence that increased plasma concentrations of CRP strongly
      predict cardiovascular death in both non-renal and renal patient populations. The
      interleukin-6 (IL-6) system activity, which is the major mediator of the acute
      phase response, is often markedly up-regulated in uremic patients and has also
      been shown to predict outcome. This raises the issue of whether or not IL-6 per
      se may contribute to increased mortality from malnutrition and atherosclerotic
      cardiovascular disease in uremic patients. The causes of elevated IL-6 levels in
      the uremic circulation are not fully understood, although a number of factors
      prevalent in uremic patients, such as hypertension, adiposity, infections, and
      chronic heart failure may all contribute. However, factors associated with the
      dialysis procedure, such as bioincompatibility and non-sterile dialysate, may
      stimulate IL-6 production. Furthermore, available evidence suggests that genetic
      factors may also have an impact on circulating plasma IL-6 levels. We advance the
      hypothesis that IL-6 may play a central role in the genesis of inflammatory
      driven malnutrition and that it may be regarded as a significant proatherogenic
      cytokine. This hypothesis may provide a rationale to test if targeted anti
      cytokine therapy may be one way to combat the unacceptable high cardiovascular
      mortality rate among dialysis patients.

PMID- 11982824
TI  - Oxidative stress in hemodialysis patients: is NADPH oxidase complex the culprit?
AB  - Oxidative stress results from an imbalance between oxidant production, including
      reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated
      compounds, and antioxidant defense mechanisms. Most reports prove that oxidative
      stress is present in ESRD patients. Several studies tend to accreditate the
      hypothesis by which oxidative stress is a strong co-factor for the development of
      complications related to long-term HD such as atherosclerosis, amyloidosis,
      malnutrition, anemia, and infection. In order to evaluate the rationale for
      curative action against oxidative damage in chronic renal failure patients, we
      reviewed the putative factors involved in this process. Antioxidant systems are
      severely impaired in uremic patients and gradually altered with the degree of
      renal failure. Moreover, the inflammatory state caused by the hemoincompatibility
      of the dialysis system plays a critical role in the activation of NADPH oxidase,
      aggravating the pro-oxidant status of uremic patients. Prevention of ROS
      overproduction by improvement of dialysis biocompatibility, an important
      component of adequate dialysis, might be completed by antioxidant
      supplementation.

PMID- 11982825
TI  - The importance of convective transport.
AB  - BACKGROUND: Despite technological advances in dialysis equipment and modalities,
      survival, morbidity, and quality of life of hemodialysis patients are still
      severely affected by acute intradialytic and long-term complications, possibly
      related to the treatment itself. Convective treatments, such as high-flux
      hemodialysis, hemodiafiltration, and hemofiltration are increasingly suggested as
      further improvements over standard diffusive hemodialysis. The membranes used for
      these techniques are high-flux semisynthetic and synthetic membranes.
      Characteristics of these membranes are high permeability, which allows convective
      removal of water and electrolytes and higher clearance of middle and large
      molecular weight solutes, and high biocompatibility, which minimizes the
      "inflammatory response" secondary to interactions between blood and the
      artificial material of the hemodialysis system. METHODS: With the specific aim of
      verifying the superiority of convective treatments in reducing morbidity and
      mortality, we performed a review of the published literature. RESULTS: Some
      epidemiological studies suggest that convective treatments reduce morbidity and
      mortality among dialysis patients. However, the results of the published
      prospective randomized controlled trials are conflicting. Moreover, since
      convective treatments are usually performed with synthetic biocompatible
      membranes, it is hard to separate the effect of convection from the effect of
      biocompatibility. CONCLUSIONS: To finally assess the effect of high-flux
      membranes on morbidity and mortality, the results of two randomized, controlled
      clinical trials (HEMO study and MPO study) specifically designed with this aim
      are needed.

PMID- 11982826
TI  - The bioartificial kidney in the treatment of acute renal failure.
AB  - The application of cell therapy to the successful substitution process of
      hemofiltration may improve the poor prognosis of patients with acute renal
      failure (ARF) in the intensive care unit. An extracorporeal bioartificial kidney
      consisting of a conventional hemofilter followed in series with a renal tubule
      assist device (RAD) has been developed. The RAD is a hemofiltration cartridge
      containing 109 human renal tubule cells grown as monolayers along the inner
      surface of the hollow fibers. The fibers provide a porous scaffold that is
      immunoprotective. The ultrafiltrate from the hemofilter is delivered to the
      luminal compartment of the RAD, and the postfiltered blood is delivered to the
      extracapillary space of the RAD. The RAD has been shown to possess multiple
      differentiated transport, metabolic, and endocrinologic activities of renal
      epithelium. These activities have been demonstrated to occur when the RAD is
      placed in the extracorporeal circuit of the bioartificial kidney in uremic
      animals. This approach may improve the current therapies used to treat patients
      with ARF because of the RAD's ability to restore lost metabolic renal function
      and cytokine balance in these desperately ill patients. In this regard, the RAD
      was able to ameliorate endotoxin and bacteremic shock in uremic animals by
      altering cytokine levels, improve mean arterial blood pressure, and maintain
      better cardiac output. With these supportive preclinical data, an FDA-approved
      phase I/II clinical trial has been initiated and early results are encouraging.

PMID- 11982827
TI  - Hemodialyzer: from macro-design to membrane nanostructure; the case of the FX
      class of hemodialyzers.
AB  - Very few innovations have characterized the different components of the
      hemodialyzers in the past 20 years. Most improvements have concerned membrane
      biocompatibility. In this article, we focus our attention on the most recent
      advances in hemodialyzer components from the macro design of the unit to the
      nanostructure of the membrane. For this purpose, we took as an example the FX
      class of hemodialyzers (FMC, Bad Homburg, Germany). The studied devices were
      chosen as an example representing some of the most recent hemodialyzers and are
      well suited to describe technical innovations occurring in the field of dialyzer
      technology. In vitro and in vivo studies were performed to characterize
      hemodynamic parameters of three models (1.4-1, 8, and 2.2 m2) and to determine
      membrane permeability, sieving coefficients, and solute clearances. The units
      were characterized by a relatively high resistance of the blood and dialysate
      compartments, leading to an increased internal filtration if compared with
      similar hemodialyzers of other series. Nevertheless, the flow distribution in
      both compartments was homogeneous and well balanced. This effect was obtained by
      the improved blood and dialysate ports design, the increased packing density of
      the fibers and a reduction of the inner diameter of the fibers from 200 to 180
      microm. At the same time, the sieving coefficients for middle-large solutes such
      as beta2 microglobulin and insulin were higher than those observed in standard
      high flux dialysers. The same effect was noted for the clearance values of these
      solutes. This was observed in the absence of significant albumin leakage. These
      results were obtained thanks to a new nano-controlled spinning technology applied
      to the fiber. The innermost layer of the membrane is in fact characterized by a
      homogeneous porosity, with increased number of pores of large dimension but a
      sharp cutoff of the membrane excluding albumin losses. In conclusion, new
      technologies and new diagnostic tools today allow for improvement in hemodialyzer
      design from its macro-components to its nano-structure. The application of
      nanotechnology to hemodialysis will probably contribute to further developments
      in hemodialyzer manufacturing.

PMID- 11982828
TI  - Control of uremic bone disease: role of vitamin D analogs.

PMID- 11982829
TI  - The calcimimetic agents: perspectives for treatment.
AB  - Recognition of the role of the extracellular calcium sensing receptor (CaR) in
      mineral metabolism has greatly improved our understanding of calcium homeostasis.
      The biology of the low affinity, G-protein-coupled CaR and the effects of its
      activation in various tissues are reviewed. Physiological roles include
      regulation of parathyroid hormone (PTH) secretion by small changes in ionized
      calcium (Ca++), and control of urinary calcium excretion with small changes in
      blood Ca++. The CaR also affects the renal handling of sodium, magnesium, and
      water. Mutations affecting the CaR that make it either less or more sensitive to
      Ca++ cause various clinical disorders. Disorders, such as primary and secondary
      hyperparathyroidism, may exhibit acquired abnormalities of the CaR. Calcimimetic
      drugs, which amplify the sensitivity of the CaR to Ca++, can suppress PTH levels
      with a resultant fall in blood Ca++. Experiences with R-568 in patients with
      secondary and primary hyperparathyroidism and parathyroid carcinoma are
      summarized. In humans with hyperparathyroidism, these agents produce a dose
      dependent fall in PTH and blood Ca++, with larger doses causing more sustained
      effects. The second generation calcimimetic, AMG 073, with a better
      pharmacokinetic profile appears to be an effective and safe treatment for
      secondary hyperparathyroidism, producing suppression of PTH levels with a
      simultaneous reduction in serum phosphorus levels and the calcium X phosphorus
      product. The advantage of controlling PTH secretion without the complications
      related to hypercalcemia, hyperphosphatemia, and increased calcium X phosphorus
      product is very promising. Treatment trials have been relatively short-term
      except for one patient treated with R-568 for more than 600 days for parathyroid
      carcinoma; nonetheless the drug had no major side effects and appeared to be
      safe. Further long-term controlled studies are underway to further confirm the
      effectiveness and safety of these compounds.

PMID- 11982830
TI  - Pathogenesis of refractory secondary hyperparathyroidism.
AB  - Calcitriol is currently used to reduce parathyroid hormone (PTH) levels in uremic
      patients. However, a significant number of patients fail to respond to calcitriol
      therapy. The data suggest that a poor response to calcitriol can be anticipated
      in patients with severe hyperparathyroidism (with a high basal PTH levels) and
      uncontrolled serum phosphate. The abnormal parathyroid response to calcitriol in
      uremic patients with severe parathyroid hyperplasia may be attributed, to a large
      extent, to the development of nodular hyperplasia as a result of clonal
      transformation from a diffuse polyclonal hyperplasia. The factors involved in the
      development of polyclonal parathyroid hyperplasia, at earlier stages of secondary
      hyperparathyroidism, appear to be the same factors that stimulate PTH secretion
      and synthesis: hypocalcemia, hyperphosphatemia and low serum calcitriol levels.
      Studies performed in vitro using parathyroid tissue from uremic patients who
      required parathyroidectomy demonstrate that in nodular hyperplasia there is an
      abnormal response to calcium and calcitriol, which suggests that there are
      factors intrinsic to the hyperplastic cell (such as decrease in calcium sensor
      receptors and vitamin D receptors) responsible for an abnormal regulation of
      parathyroid function. Accumulation of phosphate is a key factor in the
      pathogenesis of secondary hyperparathyroidism and a poor response to calcitriol
      treatment is associated with the failure to control the serum phosphorus. High
      phosphate stimulates PTH secretion as demonstrated by in vivo and in vitro
      studies. In addition, animal studies strongly suggest that phosphate increases
      parathyroid cell proliferation. There are growth-related genes potentially
      involved in uremic hyperparathyroidism; however, changes in the expression of
      these genes may be the consequence rather than the cause of parathyroid
      hyperplasia.

PMID- 11982831
TI  - Parathyroidectomy in dialysis patients.
AB  - Subtotal parathyroidectomy or total parathyroidectomy (PTx) with
      autotransplantation are surgical procedures considered while the patient is
      included on the waiting list for renal transplantation. Total PTx alone is based
      in the possibility that a fragment of tissue (nodular hyperplasia in particular)
      left in the same pathophysiological environment of long term dialysis would show
      the same behavior and reproduce in time the same clinicopathological picture. The
      persistence of uremia induces a continued growth stimulus developing residual
      hyperplasia and consequently a very high risk of recurrence. We performed total
      PTx alone in 15 uremic patients excluded for renal transplantation 10 patients
      with undetectable iPTH serum concentration and were followed up for 37 to 144
      months. There was no evidence of clinical bone disease (bone pain or fractures).
      Bone mineral lumbar spine and hip density was measured at the end of follow-up.
      The z score data showed that all patients had a bone mass similar than that
      expected for their age. Bone biopsies performed in four patients showed a uniform
      picture of low turnover without aluminium staining. Calcification of small
      arteries (digital and arcade vessels in hands and feet) were evaluated pre and
      post total PTx alone in nine out of the 10 patients with undetectable PTH levels.
      The small vessel calcification was present in five patients at the moment of PTx.
      At the end of the long term follow-up only one patient showed progression. In
      conclusion, total PTx without autotransplantation is a very effective and
      adequate treatment for refractory severe hyperparathyroidism in patients excluded
      for renal transplantation. Aluminium related osteopathy post PTx is a risk to be
      controlled with aluminium "free" dialysis water and avoiding aluminium containing
      phosphate binders.

PMID- 11982833
TI  - Postanaesthesia excitation.

PMID- 11982834
TI  - Cerebral palsy and anaesthesia.

PMID- 11982835
TI  - Preoperative coagulation tests in former preterm infants undergoing spinal
      anaesthesia.
AB  - BACKGROUND: Clinical history is insufficient to detect disorders of haemostasis
      in infants aged less than 1 year and laboratory coagulation testing is
      recommended in infants before perimedullar anaesthesia. METHODS: We designed a
      retrospective study to assess the preoperative coagulation tests [activated
      partial thromboplastin time (aPTT), prothrombin time, platelet count] performed
      in 141 former preterm infants who underwent spinal anaesthesia for elective
      inguinal hernia repair. All the infants had recovered from any significant
      medical event (necrotizing enterocolitis, intracranial haemorrhages, transfusions
      of blood products, sepsis, etc.) when they were scheduled for surgery. RESULTS:
      Mean values for aPTT were frequently abnormal (60.4%) in infants with a
      postconceptional age of less than 45 weeks. No complication related to the
      puncture or abnormal perioperative bleeding was detected. CONCLUSIONS: Other
      coagulation tests should be evaluated to assess the coagulation status in infants
      with a postconceptional age of less than 45 weeks.

PMID- 11982836
TI  - Sevoflurane versus halothane: effect of oxycodone premedication on emergence
      behaviour in children.
AB  - BACKGROUND: Clinical studies have provided conflicting conclusions about whether
      the frequency of emergence agitation is increased in children following
      sevoflurane anaesthesia. The purpose of the study was to determine a frequency
      and duration of agitation with halothane and sevoflurane anaesthesia and whether
      oxycodone premedication affected the incidence of emergence agitation in
      children. METHODS: We measured and compared halothane and sevoflurane recovery in
      130 patients using a 5-point scale measuring emergence behaviour every 10 min
      during the first 60 min of recovery or until discharge. RESULTS: We used this 5
      point scale to assess the presence or absence of emergence agitation and found a
      frequency of emergence agitation of more than 40% in children who received
      halothane and sevoflurane anaesthesia. CONCLUSIONS: Oxycodone reduced the
      frequency of agitation in children who received halothane, but not in the
      children who received sevoflurane anaesthesia.

PMID- 11982837
TI  - Diffusion of ketoprofen into the cerebrospinal fluid of young children.
AB  - BACKGROUND: The objective was to examine whether or not ketoprofen enters the
      cerebrospinal fluid after a single oral dose of 1 mg.kg-1 syrup, and to find out
      what is the lowest plasma concentration that will achieve a measurable level in
      the cerebrospinal fluid. METHODS: We measured ketoprofen concentrations both in
      plasma and cerebrospinal fluid of 10 young and healthy children (aged 9-86
      months) after surgery with spinal anaesthesia. Samples of cerebrospinal fluid
      were collected 30 min after drug administration, at the same time as venous blood
      samples. A validated high-performance liquid chromatography method with a lower
      limit of 0.02 microg x ml(-1) was used to detect ketoprofen concentrations in
      cerebrospinal fluid and plasma. RESULTS: Ketoprofen was detectable in the
      cerebrospinal fluid only in the child who had the highest plasma concentration,
      7.4 microg x ml(-1), while at plasma concentrations 6.5 microg x ml(-1) or less,
      cerebrospinal fluid (CSF) concentrations remained unmeasurable. The detected
      CSF/plasma ratio was 0.008. CONCLUSIONS: These results indicate that ketoprofen
      at a dose of 1 mg x kg(-1) is too low to produce measurable CSF levels within 30
      min of oral administration.

PMID- 11982838
TI  - Pulmonary Doppler flow velocity pattern during caudal epidural anaesthesia in
      children.
AB  - BACKGROUND: Haemodynamic effects of caudal anaesthesia in children have not been
      fully investigated. In the present study, we evaluated pulmonary haemodynamics
      during caudal anaesthesia in otherwise healthy children using Doppler
      echocardiography. METHODS: Fifteen children undergoing elective lower abdominal
      surgery were randomly divided into two groups: nine children received 1.5%
      lidocaine and six physiological saline in the caudal epidural space. General
      anaesthesia was slowly induced and maintained using nitrous oxide and sevoflurane
      in oxygen. An epidural catheter was inserted into the caudal epidural space.
      Haemodynamic data including those with echocardiography were measured before and
      after epidural administration of lidocaine or saline. RESULTS: Mean blood
      pressure, end diastolic diameter of the left ventricle, ejection fraction of the
      left ventricle and mean velocity circumferential fibre shortening did not change
      in either group following caudal epidural block. Indices of pulmonary Doppler
      flow velocity, including peak velocity of pulmonary flow and acceleration-to
      ejection time ratio, demonstrated a significant decrease after caudal lidocaine,
      but not after saline. CONCLUSIONS: Our data suggest that pulmonary Doppler flow
      velocity changes during caudal epidural anaesthesia, probably due to an increase
      in the pulmonary arterial resistance.

PMID- 11982839
TI  - Higher airway seal does not imply adequate positioning of laryngeal mask airways
      in paediatric patients.
AB  - BACKGROUND: It has been generally accepted that a higher airway seal pressure
      indicates adequate positioning of the laryngeal mask airway (LMA) in adult
      patients. The present study was undertaken to clarify whether a higher airway
      seal pressure correlates with an adequate positioning of the LMA in paediatric
      patients. METHODS: One hundred and eighty-one healthy children, aged 6-121
      months, weighing 7.0-30.0 kg, managed with size 1.5-2.5 LMAs during elective
      surgery, were enrolled in this study. LMAs were inserted without using muscle
      relaxants, and patients breathed spontaneously during surgery. At the end of
      surgery, we documented oropharyngeal sealing pressure and fibreoptic aperture
      views of the LMA. We used a new fibreoptic score evaluating the anatomical
      relationship between LMA aperture and epiglottis: 1, the aperture view covered
      with anterior epiglottis completely, but the airway staying open; 2, anterior
      epiglottis seen for more than two-thirds of the aperture view in diameter; 3,
      anterior epiglottis seen for more than one-third, but less than two-thirds of the
      aperture view in diameter; and 4, anterior epiglottis seen for less than one
      third of the aperture view in diameter. RESULTS: The oropharyngeal sealing
      pressures for each fibreoptic position, scores 1 to 4, were 17.0 +/- 6.4, 17.9 +/
      4.2, 20.1 +/- 7.3 and 17.1 +/- 6.1 cm H2O, respectively. There were no
      significant differences in sealing pressure between the four groups (P=NS).
      CONCLUSIONS: A higher airway seal is believed to be one of the clinical signs
      correlating with the correct position of an LMA. We found no relationship between
      oropharyngeal sealing pressure and LMA cuff position in paediatric patients.

PMID- 11982840
TI  - The effect of baricity of intrathecal morphine in children receiving tetracaine
      spinal anaesthesia for cardiac surgery: a preliminary report.
AB  - BACKGROUND: This prospective, randomized study examined the effect of baricity of
      intrathecal preservative-free morphine on the duration of postoperative analgesia
      and incidence of side-effects in infants and children receiving high spinal
      anaesthesia with hyperbaric tetracaine in combination with a light general
      anaesthetic. METHODS: Fourteen infants and children, aged 7-91 months, undergoing
      repair of either uncomplicated atrial or ventricular septal defects, were
      randomized to receive either 10 microg x kg(-1) of intrathecal morphine in
      combination with 0.5% tetracaine D10 (hyperbaric morphine group) or intrathecal
      morphine mixed with saline and injected sequentially after the administration of
      0.5% tetracaine D10 (hypobaric morphine group). After spinal injection, patients
      were positioned in 30 degrees of Trendelenburg for a minimum of 10 min.
      Postoperatively, patients were monitored for a minimum of 12 h. Pain scores and
      the incidence and severity of side-effects were recorded every 1 h. RESULTS: All
      patients were extubated at the conclusion of surgery without any incidence of
      respiratory depression. There was a decreased incidence of vomiting in the
      hypobaric morphine group and no significant difference in the duration of
      analgesia. CONCLUSIONS: When intrathecal morphine is administered in conjunction
      with a hyperbaric tetracaine spinal to paediatric cardiac patients in the head
      down position, sequential administration of the hypobaric solution may mitigate
      side-effects.

PMID- 11982841
TI  - Priorities for disclosure of the elements of informed consent for research: a
      comparison between parents and investigators.
AB  - BACKGROUND: Disclosure is a key element of the informed consent process. This
      study examines and compares the priorities for disclosure of the elements of
      informed consent between parents of paediatric research subjects and
      investigators. METHODS: The study sample comprised 184 parents who had been
      approached for permission to allow their child to participate in a clinical
      anaesthesia or surgery study. Parents were asked to rank 11 elements of informed
      consent that they believed were most important for them to know before allowing
      their child to participate in a research study. In addition, 38 investigators
      were asked to rank, in order of importance, the same elements that they felt were
      most important for parents to know. RESULTS: The results showed that risk was the
      most important element considered by both parents and investigators. However,
      parents placed significantly greater importance on knowledge of the potential
      benefits to their child (direct) and to other children (indirect) compared with
      investigators, and less importance on the details of the protocol and the element
      of voluntariness. CONCLUSIONS: These results demonstrated differences in the
      priorities for disclosure of the elements of consent between parents and
      investigators. As such, they may be important in directing the investigator to
      focus on the elements that are most important to parents and thus maximize their
      ability to provide truly informed consent.

PMID- 11982842
TI  - Severe head trauma in children: cranial computer tomography and clinical
      consequences.
AB  - BACKGROUND: We investigated the prognostic and therapeutic implications of
      cranial computerized tomography (CCT) examinations after severe head trauma in
      children. MATERIALS AND METHODS: The CCT scans from 248 children (aged 0.1-14
      years) during the course of treatment after severe head trauma were assessed. The
      initial CCT findings, the frequency of CCT examinations and the schedule as well
      as duration of treatment were registered. The neurological outcome was examined
      both 1 month and 1 year after the trauma. RESULTS: Approximately one-third (29%)
      of the children who suffered from severe head trauma showed no changes in the
      CCT. Furthermore, 40.3% of the children showed a singular finding in the CCT,
      whereas 30.6% of all children had a combined injury pattern. One year after
      trauma, we found no impairment of consciousness in children without pathological
      CCT findings, as well as in cases with isolated epidural and subdural
      haemorrhage. Children with massive generalized brain oedema had the poorest
      prognosis (37% died, 25% had impairment of consciousness). The outcome of
      children with parenchymal and ventricular bleeding was also unfavourable (23.1%
      and 33.3% neurological findings). Patients with focal oedema likewise had
      impairment of consciousness. An average number of 3.0 CCT per child was performed
      but numbers in single cases varied greatly (1-13 scans per individual).
      CONCLUSIONS: The initial CCT was of importance regarding further therapy,
      especially for children in need of surgical treatment. In the other cases, there
      was no direct impact from CCT findings on treatment procedures in the paediatric
      intensive care unit. The initial CCT was related to the prognosis, which can be
      poor even if there are only minimal changes in CCT, such as focal oedema or
      isolated ventricular bleeding.

PMID- 11982843
TI  - Home care for chronic respiratory failure in children: 15 years experience.
AB  - BACKGROUND: Advances in paediatric intensive care have reduced mortality but,
      unfortunately, one of the consequences is an increase in the number of patients
      with chronic diseases. It is generally agreed that home care of children
      requiring ventilatory support improves their outcomes and results in cost saving
      for the National Health Service. METHODS: Since 1985, the Children's Hospital
      Bambino Gesu of Rome has developed a program of paediatric home care. The program
      is performed by a committed Home Health Care Team (HHCT) which selects the
      eligible patients for home care and trains the families to treat their child.
      During the period January 1985 to January 2001, 53 children with chronic
      respiratory failure were included in the home care program. Of these, seven
      patients were successively excluded and six died in our intensive care unit
      (ICU), while one still lives in our ICU since 1997. The results obtained in the
      remaining 46 children are reported. RESULTS: The pathologies consisted of
      disorders of respiratory control related to brain damage (26%), upper airways
      obstructive disease (26%), spinal muscular atrophy (22%), myopathies and muscular
      dystrophies (6.5%), bronchopulmonary dysplasia (6.5%), tracheomalacia (6.5%),
      central hypoventilation syndrome (4.3%) and progressive congenital scoliosis
      (2.2%). Of these 46 patients, 34 children are mechanically ventilated and the
      median of their ICU stay was 109.5 days (range 54-214 days), while the remaining
      12 children were breathing spontaneously and the median of their ICU stay was
      90.5 days (range 61-134 days). We temporarily readmitted six patients to our ICU
      to perform scheduled otolaryngological surgery, eight patients for acute
      respiratory infections and two patients for deterioration of their neurological
      status due to high pressure hydrocephalus for placement of a ventriculoperitoneal
      shunt; these 16 patients were discharged back home again. Two other patients were
      readmitted for deterioration of their chronic disease and died in our ICU, while
      seven patients died at home. CONCLUSIONS: Thirty-seven children are still alive
      at home and four of them improved their respiratory condition so that it was
      possible to remove the tracheostomy tube. Our oldest patient has now achieved 15
      years of mechanical ventilation at home.

PMID- 11982844
TI  - Myotonia dystrophica and spinal surgery.
AB  - Two cases of patients suffering from the congenital form of myotonia dystrophica
      under going spinal surgery are presented. Both patients had major complications,
      including cardiac arrhythmias, postoperative wound infection and more minor
      complications, such as sedation and opioid sensitivity. However, the most notable
      complication resulting in long-term morbidity was the deterioration of bulbar
      muscular function in one of the patients. This resulted in recurrent aspiration
      pneumonia and the need for a tracheostomy. This serious complication has not
      previously been reported following surgery.

PMID- 11982845
TI  - Traumatic aneurysm of the internal carotid artery in an infant: a surprise
      diagnosis.
AB  - Isolated aneurysm of the extracranial section of the internal carotid artery has
      been reported in children but never, to our knowledge, in an infant. It can
      represent a major anaesthetic challenge with compromise of both airway and
      cerebral perfusion and the associated risks of rupture. We report on an 11-month
      old infant, who had undergone an examination under anaesthesia of her nose and
      throat for epistaxis and gastrointestinal endoscopy due to apparent
      gastrointestinal bleeding shortly before presenting to us with signs of rapidly
      progressive upper airway obstruction. Emergency examination under anaesthesia
      revealed a large pulsatile mass in the posterior nasopharynx which, on subsequent
      radiological investigation, was revealed to be a large pseudoaneurysm of the
      right internal carotid artery, obstructing distal flow. An apparently minor
      episode of trauma had occurred around the time of the first nosebleed; she had
      allegedly fallen onto her face with a spoon in her mouth.

PMID- 11982846
TI  - Venous air embolus during arthrography in a child: vital signs changes
      illustrated by the automated data recording system.
AB  - We describe an 18-month-old boy who suffered venous air embolism during an
      arthrogram. Dangers associated with air injection are emphasized, illustrating
      the importance of careful monitoring to detect adverse events. We recommend
      caution when employing this method of hip joint evaluation.

PMID- 11982847
TI  - Anaesthetic implications of Nager syndrome.
AB  - Nager acrofacial dysostosis is an oromandibular hypogenesis syndrome with
      associated limb abnormalities. Although it shares some phenotypic features with
      Treacher-Collins syndrome, it is recognized as a separate disorder. The physical
      features of Nager syndrome include down slanted palpebral fissures, malar
      hypoplasia, a high nasal bridge, atretic external auditory canals, cleft palate
      and micrognathia. Preaxial limb malformations include absent or hypoplastic
      thumbs, hypoplasia of the radius and shortened humeral bones. Of primary concern
      to the anaesthetist are the midface and mandibular manifestations which may
      complicate perioperative airway management. These problems may also manifest in
      the postoperative period with airway obstruction. Associated defects have
      included vertebral malformations with reports of cervical spine involvement,
      congenital cardiac defects and upper limb defects affecting the preaxial or
      radial side. We describe a 7-year-old boy with Nager syndrome who required
      anaesthetic care during placement of a syringopleural shunt for drainage of a
      spinal cord syrinx. The perioperative implications of this disorder are reviewed.

PMID- 11982848
TI  - Use of laryngeal mask airway for prolonged ventilatory support in a preterm
      newborn.
AB  - We present the case report of a preterm, low weight newborn with dysmorphic
      features and micrognathia in whom a laryngeal mask airway was inserted and
      maintained for 44 h for ventilatory support after several failed intubations. No
      complications associated with laryngeal mask airway use were apparent.

PMID- 11982849
TI  - The use of methohexital during neonatal cardioversion.
AB  - We report on the use of methohexital during elective neonatal direct current
      cardioversion. In contrast with the available data on cardiac management in
      neonates with supraventricular tachycardia and the guidelines on anaesthetic
      management during cardioversion in adults, data on anaesthetic management in
      neonates are still lacking. Methohexital might be an option for procedural
      sedation and anaesthesia during elective cardioversion in neonates.

PMID- 11982850
TI  - Anaesthetic implications of von Recklinghausen's neurofibromatosis.

PMID- 11982851
TI  - Rett syndrome: anaesthesia management.

PMID- 11982852
TI  - Prolonged laryngeal mask anaesthesia in a spontaneously breathing child.

PMID- 11982853
TI  - Anaesthesiological considerations in Costello syndrome.

PMID- 11982854
TI  - Difficult airway management of a child impaled through the neck.

PMID- 11982856
TI  - Arginase I induction in macrophages, triggered by Th2-type cytokines, supports
      the growth of intracellular Leishmania parasites.
AB  - Leishmania spp. are intracellular protozoan parasites that invade and replicate
      within macrophages. In a previous report, we have demonstrated that the growth of
      intracellular amastigotes could be controlled by inhibition of arginase. This
      enzyme, induced in host cells by Th2 cytokines, synthesizes L-ornithine which can
      be used by parasites to generate polyamines and proliferate. In this study, we
      have designed experiments to better analyse the dependence of parasite
      proliferation on arginase induction in infected macrophages. Treatment of
      Leishmania major-infected BALB/c macrophages with interleukin (IL)-4, IL-10 or
      transforming growth factor-beta, which are all inducers of arginase I in murine
      macrophages, led to a proportional increase in the number of intracellular
      amastigotes. Moreover, parasite proliferation and arginase activity levels in
      macrophages from the susceptible BALB/c mice were significantly higher than those
      from infected C57BL/6 cells when treated with identical doses of these cytokines,
      indicating that a strong correlation exist between the permissibility of host
      cells to L. major infection and the induction of arginase I in macrophages.
      Specific inhibition of arginase by N(omega)-hydroxy-nor-L-arginine (nor-LOHA)
      reverted growth, while L-ornithine and putrescine promoted parasite
      proliferation, indicating that the parasite cell division depends critically on
      the level of L-ornithine available in the host. Therefore, arginase induction in
      the context of a Th2 predominant response might be a contributor to
      susceptibility in leishmaniasis.

PMID- 11982857
TI  - Effect of oxygen radicals and differential expression of catalase and superoxide
      dismutase in adult Heligmosomoides polygyrus during primary infections in mice
      with differing response phenotypes.
AB  - The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was
      examined by assessing parasite survival following incubation with hydrogen
      peroxide and acetaldehyde/xanthine oxidase, generators of H2O2 and H2O2/O2(-),
      respectively. H. polygyrus worms could tolerate levels of < 0.25 mM hydrogen
      peroxide and < 0.5 mM/20 mU acetaldehyde/xanthine oxidase for 20 h, but, at
      higher concentrations, marked sex-dependent susceptibility was observed, with
      males being more sensitive to H2O2 and O2(-) than female worms. The ability to
      evade free radical-mediated damage was also evaluated by measuring superoxide
      dismutase (SOD) and catalase levels in worms isolated at different time points
      from four strains of mice with differing resistance phenotypes. Levels of both
      catalase and SOD in female worms isolated from 'rapid'[(SWRxSJL)F1], 'fast' (SWR)
      or 'intermediate' (BALB/c), but not 'slow' (C57BL/10), responder mice showed a
      strain-dependent increase with time. Moreover, male worms were rejected faster
      than female worms in the 'rapid', 'fast' and 'intermediate' responder strains of
      mice. The results suggest that host-derived free radicals can damage adult worms
      and that female worms can increase production of their scavenging enzymes in
      response to the immune onslaught that eventually leads to worm expulsion in mice
      with 'fast', 'rapid' or 'intermediate' response phenotypes.

PMID- 11982858
TI  - The influence of gammadelta T cells on the CD4+ T cell and antibody response
      during a primary Plasmodium chabaudi chabaudi infection in mice.
AB  - A primary infection with Plasmodium chabaudi chabaudi (AS) is characterized by an
      expansion of gammadelta cells after the acute phase of infection in mice. This is
      particularly marked during chronic infections in B cell-deficient mice.
      Infections in gammadelta T cell-deficient mice suggest that, although these cells
      play some role in the control of parasitaemia and can produce interferon-gamma,
      they do not appear to be involved in the development of hypoglycaemia, loss of
      weight and temperature during a P. c. chabaudi infection. However, gammadelta T
      cells do influence the nature of the CD4+ T cell response during infection since,
      in their absence, Th2-like responses, such as interleukin (IL)-4 production and
      help for malaria-specific antibody responses, are more pronounced. This
      alteration in CD4+ T cells is reflected in a more rapid and greater
      immunoglobulin (Ig)G1 and IgG3 antibody response to the parasite. The large
      gammadelta T cell expansion normally observed in infected B cell-deficient mice
      did not take place in the absence of IL-2, and double-knockout mice lacking both
      B cells and functional IL-2 were highly susceptible to lethal infection with P.
      c. chabaudi. The majority of the single IL-2 knockout mice, in contrast, were
      able to control and clear a primary infection, suggesting that for the CD4+ T
      cell and antibody response, IL-2 could be replaced by other cytokines.

PMID- 11982859
TI  - Recognition of synthetic polypeptides corresponding to the N- and C-terminal
      fragments of Plasmodium falciparum Exp-1 by T-cells and plasma from human donors
      from African endemic areas.
AB  - The present work describes the recognition of three synthetic polypeptides
      encompassing the N- and C-terminal regions of the transmembrane Exp-1 protein of
      the parasite Plasmodium falciparum by plasma and peripheral blood mononuclear
      cells from naturally exposed individuals living in African endemic areas. The
      three polypeptides comprise the sequences 23-105, 73-162 and 101-162, and overlap
      at the transmembrane domain (73-105). Thus, they permitted characterization of
      the immune response specific to the N- and C-terminal domains in an independent
      fashion. Two different populations were evaluated, one in the village of Safo in
      Mali and the other in the villages of Somnaway, Kabortenga and Toussouktenga in
      Burkina Faso. Antibodies to the sequence 73-162 of Pf Exp-1 were found in 70% of
      adult Mali donors and in all of the donors tested from Burkina Faso. Strikingly,
      the N-terminal fragment Pf Exp-1 23-105 was only weakly recognized by a few
      donors. Evaluation of the T-cell response indicated that the peptide Pf Exp-1 23
      105 was more potent than Pf Exp-1 73-162 in inducing a proliferative response. A
      correlation between peptide-specific interferon-gamma and interleukin-6
      production and proliferation to peptide Pf Exp-1 23-105 was observed. Further
      studies are needed to evaluate this molecule as a vaccine candidate.

PMID- 11982860
TI  - Experimental Schistosomiasis japonica in the pig: immunohistology of the hepatic
      egg granuloma.
AB  - Use of the pig as an animal model in schistosomiasis research is increasing, but
      knowledge of the porcine immune response to schistosome infection is still very
      limited. We investigated the immunohistology of different maturation stages of
      the Schistosoma japonicum egg granuloma in pigs. Liver sections from pigs
      experimentally infected with S.japonicum for 9, 12 or 21 weeks were examined by
      immunohistochemistry using a three-step streptavidin-biotin
      complex/immunoperoxidase method or a two-step alkaline phosphatase-mediated
      system. All granulomas showed marked expression of major histocompatibility
      complex (MHC) class II in epithelioid macrophages and were dominated by T
      lymphocytes, comprising both CD4+ and CD8+ phenotypes, with consistently higher
      proportions noted for CD8+ cells. B lymphocytes, as identified by expression of
      CD21, were confined to lymphoid nodular structures primarily associated with
      mature granulomas. Early and mature granulomas contained numerous immunoglobulin
      (Ig)G+ plasma cells. Significant differences in immunohistology related to
      duration of infection were not observed. The results indicate that all stages of
      the hepatic S.japonicum egg granuloma in the pig manifests MHC class II-dependent
      CD4+ T cell activity concomitant with infiltration of CD8+ T cells. B cell
      activity preceding the effector cell stage appears to occur in granuloma
      associated lymphoid nodules, whereas antibody, mainly IgG, is produced within the
      granuloma.

PMID- 11982862
TI  - Coronary diameter in normal infants, children and patients with Kawasaki disease.
AB  - BACKGROUND: The coronary assessments in Kawasaki disease are mainly based on the
      Japanese Ministry of Health and Welfare criteria, which is simply classified
      according to the patient's age, over 5 years and less than 4-years-old. METHODS:
      We obtained normal values of coronary diameters adjusted for the body surface
      area and for the coronary anatomical site from 71 healthy children using 2-D
      echocardiography. We also studied patients with Kawasaki disease at three stages
      from the onset of illness: (i) 43 patients at admission; (ii) the subsequent 2-3
      weeks; and (iii) 62 children followed at a clinic, for a median 2.2 years after
      the onset. No patients showed any coronary abnormalities by several echographic
      exams. RESULTS: The coronary diameters were strongly correlated with the body
      surface area (r = 0.81 in left main, r = 0.89 in proximal right, r = 0.89 in left
      anterior descending artery). The coronary diameters in the patient groups at
      admission and at 2-3 weeks later were significantly larger than those in the
      normal group (P < 0.01). Although the coronary diameters in the follow-up group
      did not show a significant difference compared with those of normal, 19% retained
      their coronary diameters at greater than two standard deviations above the
      expected mean in at least one coronary artery. CONCLUSIONS: The more strictly
      defined criteria adjusted for body size and for the anatomical site should be
      used to detect the subtle changes and to prevent the misclassification of the
      coronary artery abnormalities in KD.

PMID- 11982863
TI  - Increased production of serum IgA-class antibody to lipid A in Kawasaki disease.
AB  - BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. To investigate
      whether a conventional bacterial antigen is involved in the pathogenesis of KD,
      we studied the serum response to lipopolysaccharide (LPS). METHODS: We measured
      the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic
      site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11
      patients with Gram-negative bacterial infection (GNBI), 27 healthy children and
      12 healthy adults. RESULTS: The serum levels of anti-lipid A IgG, IgM and IgA
      tended to increase with advancing age in healthy children older than 6 months of
      age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean
      levels of anti-lipid A IgM and IgA in the acute phase of KD were found to
      increase significantly, in comparison to the age-matched controls. Furthermore,
      the mean level of anti-lipid A IgA also showed a significant increase from the
      acute to the subacute phases of KD. Regarding the IgA-subclass response, higher
      titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the
      IgA1 subclass. CONCLUSION: These findings indicate that KD patients demonstrate
      an intense response to lipid A in the IgA, especially IgA2-subclass, thus
      suggesting that an unusual activation of the mucosal immune response to a
      ubiquitous antigen derived from Gram-negative bacteria may be involved in the
      pathogenesis of KD.

PMID- 11982864
TI  - Longitudinal estimation of signal-averaged electrocardiograms in patients with
      Kawasaki disease.
AB  - BACKGROUND: Myocarditis associated with Kawasaki (KD) disease is prominent, but
      rarely detected by conventional methods. The hypothesis of this study is to see
      if signal-averaged electrocardiogram can detect myocarditis with KD. METHODS: We
      obtained signal-averaged electrocardiograms from 71 patients with KD (mean age
      2.8 +/- 2.9 years) in the acute (1st-4th week), subacute (5-7th week), and
      chronic (8th week or later) phases (mean study period 3.5 +/- 1.7 years). Sixteen
      patients who had pericardial effusion, bundle branch block or myocardial ischemia
      were excluded from this study. The results were compared with those of Holter and
      12-lead electrocardiograms, echocardiography and serum myocardial enzymes. They
      were also contrasted with the course of each patient. RESULTS: The incidence of
      abnormal findings on signal-averaged electrocardiogram was 18.2% in the acute
      phase versus 10.9% in the subacute and chronic phases. It differed significantly
      higher than the other conventional tests (P < 0.05). Four patients had
      abnormalities of signal-averaged electrocardiograms through all three phases.
      Among these four, two had reduced left ventricular contractility. However, these
      changes were transient and resolved in the subacute phase. All patients had good
      courses and no residue. CONCLUSION: This study shows the possibility that signal
      averaged electrocardiogram is more useful to detect myocarditis associated with
      KD than the other conventional tests. However, we could not define the prognostic
      value of abnormal signal-averaged electrocardiograms during this study period.

PMID- 11982865
TI  - Systolic and diastolic function in children with chronic renal failure.
AB  - BACKGROUND: Cardiovascular complications are the most frequent cause of death in
      patients with end-stage renal failure (ESRF). We aimed to investigate systolic
      and diastolic functions in children with ESRF. METHODS: Thirty-nine children with
      ESRF (17 on continuous ambulatory peritoneal dialysis (CAPD), eight on
      hemodialysis and 14 on predialysis) were examined to assess systolic and
      diastolic functions by echocardiography and ultrasound Doppler. Left ventricular
      systolic and diastolic functions were measured both in patients and age-matched
      healthy controls (n = 20) and the indices of cardiac performance were compared.
      RESULTS: Increased left ventricular mass index (LVMI) and decreased volume/mass
      ratio with normal systolic left ventricular function was found in patients, as
      compared with controls. Left ventricular diastolic dysfunction was observed in
      dialysis patients. In most of these patients, left ventricular isovolumic
      relaxation time was prolonged, except in CAPD patients. The peak of late
      diastolic flow (A) velocities were increased with a reduction of the early
      diastolic flow velocity (E)--the E/A ratio. The E velocities were unchanged in
      all patients as compared with controls. Our data indicated an abnormality of
      myocardial relaxation in patients with ESRF. We found no relationship between E/A
      ratio and LVMI. Among three groups of patients, the LVMI and diastolic
      abnormalities were highest in the hemodialysis group indicative of poor control
      of hypervolemia and hypertension. CONCLUSIONS: The technique of CAPD has some
      advantages as a renal replacement therapy for preserving cardiac functions as
      compared with hemodialysis. However, it must be remembered that patients with
      hemodialysis have features that effects cardiac status, such as higher volume
      load and higher afterload (hypertension).

PMID- 11982866
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a
      pediatric ward.
AB  - BACKGROUND: Nosocomial infections caused by methicillin-resistant Staphylococcus
      aureus (MRSA) are one of the most serious problems in pediatric wards.
      Epidemiological analysis of strains isolated in the ward is essential for
      infection control. There have been few reports in which a molecular
      epidemiological study of MRSA was performed in pediatric wards. METHODS: Fifty
      six MRSA strains isolated in the pediatric ward of Asahikawa Medical College
      Hospital between 1995 and 1997 were studied. Fifty-two and four isolates were
      obtained from 27 patients and from two medical staff members, respectively. Forty
      one isolates were regarded as colonizing strains and 15 were causes of
      infections. Genotypes of the isolates were investigated by pulsed-field gel
      electrophoresis (PFGE). RESULTS: The PFGE patterns of 56 isolates were classified
      into nine types: type A, its subtypes, A1 and A2, and types B through to G.
      Seventeen isolates were type A, 32 were type A1, and one of each type of A2 and B
      through to G were identified. Fifty of 56 isolates, which were isolated from 24
      of 29 cases, belonged to type A or its subtypes. CONCLUSIONS: The predominant
      strain of MRSA isolates in the pediatric ward was a certain strain that may be
      originated from the one clone. Cross-infection control therefore is the major
      procedure in the prevention of MRSA dissemination in the ward.

PMID- 11982867
TI  - Serum cystatin-C values in children by age and their fluctuation during
      dehydration.
AB  - BACKGROUND: Serum creatinine level (Cr) is extensively used as an index of
      glomerular filtration rate (GFR) with bedside patients. As serum Cr level differ
      by the muscle volume, the use of serum Cr as an index of GFR has long been
      considered problematic in children. METHODS: The subjects of this study were 135
      healthy children aged from 1 to 15-years-old. As a pathological condition, the
      changes in serum cystatin C (Cys-C) in the children whose blood urea nitrogen
      exceeded 20 mg/dL during the acute stage of dehydration were also investigated.
      RESULTS: The mean serum Cys-C value was 0.67 +/- 0.19 mg/L on the whole. There
      was not any male-female difference. The mean serum Cys-C values of the 12 cases
      in the acute stage and the recovery stage were 0.61 +/- 0.12 mg/L and 0.64 +/-
      0.14 mg/L, respectively, indicating no significant difference. CONCLUSION: Serum
      Cys-C is considered as a favorable index of GFR in children because it is not
      influenced by age and sex. As it is not influenced by the prerenal factors
      either, serum Cys-C is useful in children over 1-years-old.

PMID- 11982868
TI  - Alphabeta and gammadelta T cell subsets in chronic renal failure in children on
      dialysis treatment.
AB  - BACKGROUND: Impaired immunity, particularly cell-mediated, is one of the features
      of chronic renal failure. This also concerns impaired T cell dependent
      responsiveness. METHODS: The expression of T cell surface antigens (CD3, CD25,
      TCRalphabeta, TCRgammadelta) was evaluated on peripheral blood (PB) mononuclear
      cells using two-color flow cytometry in 10 children on continuous ambulatory
      peritoneal dialysis (CAPD) and in 13 children on maintenance hemodialysis (HD)
      with polysulfone and cuprophane dialysers. RESULTS: In HD children absolute
      numbers of leukocytes, lymphocytes, CD3+, alphabeta, gammadelta T cells and a
      percentage of gammadelta T cells were decreased versus healthy children. Also, we
      observed a relative increase of CD3+, CD3+/CD25+ and alphabeta T cells after
      sessions with cuprophane membranes, and an increase of CD3+/CD25+, alphabeta T
      cell percentages after sessions with the polysulfone membranes. Additionally we
      found a decrease of both relative and absolute numbers of gammadelta T cells
      after HD with polysulfone. In CAPD children we found declined absolute numbers of
      total lymphocytes, CD3+ and alphabeta T cells and higher relative values of CD3+
      and alphabeta T cells versus controls. CONCLUSIONS: The T cell depletion in
      chronic renal failure (CRF) patients primarily results from uremic-related
      toxicities, rather than from CAPD or HD-related incompatibilities. We showed a
      significant decrease of gammadelta T cells in CRF patients on HD, that may be
      partly responsible for impaired T-dependent responsiveness in that group. The
      intradialytic changes of gammadelta Tcells may result from a different degree of
      biocompatibility during the application of various dialysis membranes.

PMID- 11982869
TI  - Unexplained subdural hematoma in young children: is it always child abuse?
AB  - BACKGROUND: In the published reports of the developed society, subdural hematoma
      and/or retinal hemorrhages, in the absence of documented history of major trauma,
      should be considered diagnostic of child abuse. Many people used the above
      criteria for diagnosis, but subsequently found that retinal hemorrhages were more
      common in non-accidental injuries (NAI). To what extent is the proposed
      pathognomonic association between unexplained subdural hematoma/retinal
      hemorrhages and child abuse a self-fulfilling prophecy? METHODS: Clinical details
      of nine children under 2 years with unexplained subdural hematoma admitted to
      Prince of Wales Hospital between 1995 and 1998 were reviewed. RESULTS: Four had
      no other physical signs of injury, five had retinal hemorrhages and one had
      multiple bruises over the body. Following multidisciplinary case conferences for
      seven children, a diagnosis of NAI was concluded in four cases, but in no case
      could the abuser be definitely identified. Clinical outcome was poor with seven
      children showing either profound disability (n = 5) or evidence of developmental
      delay (n = 2). CONCLUSION: In this series, NAI were not established in three of
      the seven cases. Did we underdiagnose child abuse in these cases? Despite a
      magnitude of opinion to the contrary, the issue of whether "trivial" head injury
      can cause subdural hemorrhages and/or retinal hemorrhages is yet unresolved.
      Clearly much more information on this very sensitive and serious issue is
      required and these data should be collected with an open mind.

PMID- 11982870
TI  - Prophylactic effect of inactivated influenza vaccine on young children.
AB  - BACKGROUND: The effectiveness of inactivated influenza vaccine in healthy infants
      and young children has been controversial. The aim of this study was to determine
      the prophylactic effect of inactivated influenza vaccine in young children.
      METHODS: Eighty-six healthy infants and children younger than 7-years-old were
      immunized by a subcutaneous injection of inactivated influenza vaccine before the
      1999/2000 influenza season. Ninety-four age-matched children were randomly
      assigned as the control. These children were followed-up from January to April,
      2000. A diagnosis of influenza A virus infection was made rapidly by a positive
      result of the the enzyme immunoassay membrane test using enzyme-conjugated
      monoclonal antibodies specific for a conserved epitope of influenza A
      nucleoprotein. The incidence of influenza A infection was compared and
      statistically assessed. RESULTS: The prevalence of influenza A virus infection,
      diagnosed by the influenza A rapid detection test, was 5.8% in the vaccine group
      and 17.0% in the control group, that is significantly lower in the vaccine
      receiving group than the non-receiving group (P = 0.016). However, four out of
      five infected children in the vaccine group were younger than 2-years-old.
      CONCLUSION: We conclude that inactivated influenza vaccine reduces the incidence
      of influenza A virus infection in 2-6-year-old children.

PMID- 11982871
TI  - Prevalence of breast-feeding and its correlates in Ho Chi Minh City, Vietnam.
AB  - BACKGROUND: The health benefits of breast-feeding are widely acknowledged and
      breast-feeding is crucial for the survival of the infants in developing
      countries. The present study aims to elucidate the prevalence of breast-feeding
      and the possible risk factors affecting the breast-feeding of infants at the age
      of 3 months in Ho Chi Minh City, Vietnam after the World Health Organization and
      the United Nations Children's Fund launched "the Baby-Friendly Hospital"
      Initiative in 1989. METHODS: A cross-sectional study was conducted in the urban
      areas of Ho Chi Minh City, Vietnam in February, 2000. Two hundred and sixty
      mother-infant pairs were conveniently recruited in three child health centers in
      Ho Chi Minh City. Mothers of infants aged 6-12 months were interviewed and
      completed a well-structured questionnaire regarding the feeding types of the
      infant, the maternal knowledge, attitudes and behaviors related to breast
      feeding. RESULTS: The results indicated that although about 86.4% newborns in the
      maternity wards and 88.5% infants at 3 months were at least partially fed with
      breast milk, the prevalence of breast-feeding were 57.4 and 53.1%, respectively.
      About 47.5% newborns were fed with breast milk in the first feeding. The
      multivariate logistic regression analysis shows that the risk factors for the
      introduction of breast milk substitutes at 3 months of age were maternal
      antenatal plan of mixed or artificial feeding (odds ratio (OR) = 6.59, 95%
      confidence interval (CI): 3.18-13.64, P < 0.001) and the supplement of breast
      milk substitutes in the maternity ward (OR = 4.30, 95% CI: 2.10-8.77, P < 0.001).
      Higher maternal education levels were beneficial to the continuation of breast
      feeding. About 18.5% mothers had attended antenatal breast-feeding education.
      Most of the mothers (94.1%) and families (95.4%) indicated supportive attitudes
      to breast-feeding. CONCLUSION: The prevalence of breast-feeding was relatively
      low in Ho Chi Minh City, Vietnam. The antenatal education in breast-feeding needs
      to be improved and the implementation of the "Baby-Friendly Hospital" policy
      needs to be strengthened.

PMID- 11982872
TI  - Fetal growth and the timing of exposure to maternal smoking.
AB  - BACKGROUND: Maternal smoking during the third trimester reduces the birthweight
      of the full-term neonate. We assessed the relationship between the timing of
      exposure to maternal smoking, gestational period, weight and body length for both
      full-term and preterm neonates. METHODS: A retrospective study with a
      questionnaire was conducted in 1194 infants who participated in the official
      medical examination for 3-year-old infants. RESULTS: The risk of preterm birth
      from mothers who smoked during any trimesters was significantly increased. The
      body length of neonates whose mothers smoked during the third trimester was
      shorter than that of neonates whose mothers did not smoke during the third
      trimester. The weight of full-term neonates whose mothers smoked during the third
      trimester was lighter than that of neonates whose mothers did not smoke during
      the third trimester. CONCLUSIONS: Maternal smoking during any trimesters
      increased the risk of preterm birth. Maternal smoking during the third trimester
      reduced the body length of both full-term and preterm neonates, and the
      birthweight of the full-term neonate in a somewhat dose-dependent manner.

PMID- 11982873
TI  - Effects of child seats on the cardiorespiratory function of newborns.
AB  - BACKGROUND: This study aims to determine the effect of differently positioned
      infant car seats on cardio-respiratory parameters in healthy full-term newborns.
      METHODS: We examined 15 healthy term newborns for respiratory compromise due to
      normal restraint in a recommended infant car seat. There are currently two types
      of car seats available in Japan: a chair-shaped car seat and a bed-shaped car
      seat. Using a sleep apnea recorder, we simultaneously monitored heart rate,
      percutaneous oxygen saturation, chest impedance and nasal airflow in infants
      placed in each of the car seats and also placed in the supine position on a
      nursery cot. Episodes of oxygen desaturation below 95% and longer than 10 s (mild
      desaturation) and below 90% longer and than 10 s (moderate desaturation) were
      evaluated over 30 min observation period. RESULTS: The amount of time infants
      spent in a sleep state was significantly longer in the car seats than it was on
      the cot (P = 0.0015 for bed-shaped, P = 0.0012 for chair-shaped) and there was no
      difference in this measure between the two types of car safety seats. Mean of
      oxygen saturation with the chair-shaped car seat (95.8%) was significantly lower
      than that with the bed-shaped car seat (98.8%) (P = 0.0008). Newborn infants laid
      on the cot showed no episodes of desaturation. Newborn infants placed in the
      chair-shaped car seat had significantly more episodes of mild desaturation (mean,
      7.33 times in nine of 15 infants), whereas in the bed-shaped seat observed only
      once each in two infants (P = 0.008). Moderate desaturation was observed in four
      of 15 infants in the chair-shaped car seat, whereas not observed in the bed
      shaped car seat (P = 0.068). CONCLUSION: The results suggest that prior to
      discharge the degree of oxygen desaturation that occurs when an infant is placed
      in a chair-style car seat should be checked.

PMID- 11982874
TI  - Incidence of acute respiratory infections and the relationship with some factors
      in infancy in Antalya, Turkey.
AB  - BACKGROUND: Acute respiratory infections (ARI) are one of the major problems of
      childhood in developing countries. The objective of the study was to obtain the
      incidence of ARI and its risk factors in Antalya, Turkey. METHODS: We carried out
      a prospective cohort study on 204 infants who were born between 1 November and 31
      December 1997, in the area of two primary health-care units in the Antalya city
      center. The research group was followed periodically every 2 months by home
      visits and the infants were investigated to determine their symptoms of ARI. The
      weight and length of children were measured in every home visit. Additional
      questions about socioeconomic status, some environmental characteristics, and
      nutrition practice were asked. Data were entered into the computer and the Z
      scores were calculated by the Epi Info 5 package program. The incidence rates,
      relative risks and confidence intervals were calculated by Microsoft Excel
      version 5.0 program. RESULTS: The incidence of ARI was 6.53 episodes per child
      per year among the children in the research group. The factors that influenced
      the incidence of ARI were lack of mother's and father's education, heating by
      wood stove, being a low-birthweight infant, not being completely breast-fed in
      the first 4 months of life and being stunted. There were no associations between
      the number of persons per room or smoking status of family members with ARI
      incidence. CONCLUSION: Our results demonstrated that ARI were also associated
      with some socioeconomic, environmental and nutritional status characteristics
      such as paternal education, house ownership, breast-feeding, stunting,
      prematurity and burning of biomass fuels in Turkey.

PMID- 11982875
TI  - Effect of hemodialysis on carnitine levels in children with chronic renal
      failure.
AB  - BACKGROUND: Impaired structural and metabolic integrity of the kidney in chronic
      renal failure (CRF) effects carnitine metabolism by means of many factors.
      Depletion due to hemodialysis (HD) is one of the major concerns. The aim of the
      study was to investigate the effects of chronic renal failure and HD on plasma
      free carnitine (FC) concentrations in children. METHODS: Plasma FC concentrations
      were measured in age-matched 14 undialyzed patients, 20 dialyzed patients and 12
      healthy children. In the HD group, measurements were done pre- and postdialysis
      and an hour after ceasing HD. None of the children have been receiving exogenous
      l-carnitine replacement. RESULTS: Plasma FC concentrations on either HD or
      conservative treatment were found to be decreased as compared to the healthy
      subjects (P < 0.001 and P = 0.001, respectively). The patients on HD had lower
      levels of plasma FC at the predialysis period than those on conservative
      treatment (P = 0.01). The FC levels significantly dropped at the postdialysis
      period as compared to those at the predialysis period (P < 0.001), but recovered
      at 1 h after ceasing HD. The mean duration of HD did not correlate with plasma FC
      levels at predialysis period. CONCLUSIONS: Children with CRF, either dialyzed or
      undialyzed, have decreased plasma FC levels. Hemo-dialysis treatment
      significantly depletes plasma FC concentrations during the procedure, but
      predialysis levels are reached 1 hr after ceasing HD.

PMID- 11982876
TI  - Free carnitine levels in children with steroid-sensitive nephrotic syndrome.
AB  - BACKGROUND: Carnitine transports long-chain fatty acids across the inner
      mitochondrial membrane. Carnitine metabolism is disturbed in some renal diseases,
      such as chronic renal failure. Previous studies have shown that children had
      normal serum free carnitine (FC) and total carnitine levels in idiopathic
      nephrotic syndrome, IgA nephropathy, non-IgA nephropathy and focal segmental
      glomerulosclerosis. The aim of the present study was to determine FC
      concentrations in plasma and urine during acute and remission periods of steroid
      sensitive nephrotic syndrome (SSNS) and its association with hyperlipidemia.
      METHODS: Plasma and urinary FC concentrations were assayed in 15 children with
      SSNS in acute and in 16 children in remission period. Six of them were followed
      up longitudinally in both periods. RESULTS: Plasma FC concentrations were
      significantly higher in the acute period of the disease than in the remission
      period and of the controls. The patients had lower FC levels in the remission
      period as compared to the controls. Urinary FC concentration was decreased in
      acute disease period when compared to the remission period and the controls. The
      FC concentrations in plasma and urine did not correlate with each other. Plasma
      FC exhibited significant positive correlation with low-density lipoprotein
      cholesterol, total cholesterol and trygliceride, but negative correlation with
      high-density lipoprotein cholesterol. CONCLUSIONS: The present study showed
      disturbed FC concentration in SSNS. Increased plasma and decreased urinary FC
      levels in acute disease might be associated with its altered renal handling or
      some extrarenal factors such as hyperlipidemia.

PMID- 11982877
TI  - Treatment of pneumothorax in newborns: use of venous catheter versus chest tube.
AB  - BACKGROUND: The traditional treatment for pneumothorax is tube thoracostomy.
      Chest tube placement often involves complications, particularly in newborns. The
      aim of this study is to introduce the method of air drainage with venous catheter
      and to compare two different methods, chest tube placement and venous catheter
      insertion, in the treatment of pneumothorax in newborns. METHODS: We treated 72
      newborn patients with pneumothorax over a 4-year period in neonatal intensive
      care units at two different medical centers. We randomly divided the patients
      into two groups. In group I, we treated the patients with chest tube placement
      technique. We used 18-gauge venous catheter connected to an underwater system to
      drain air in group II patients. The duration of the procedure, the period of time
      that the chest tube or catheter was left in place, and the complications
      associated with the two different procedures were statistically compared.
      RESULTS: The time required to perform the venous catheter procedure was
      significantly shorter than that for chest tube placement (P < 0.05). The duration
      of the device in place was also significantly shorter in group II than group I (P
      < 0.05). Only two minor complications were recorded in patients who underwent
      venous catheter placement, and this group's complication rate was significantly
      lower than the rate in the chest tube group (P < 0.05). CONCLUSION: Insertion of
      a venous catheter is a safe alternative to chest tube placement as a method of
      draining air from newborn patients with pneumothorax. This is an easy and quick
      bedside procedure and is particularly useful for newborn patients that require
      immediate air drainage.

PMID- 11982878
TI  - Central venous catheters in pediatric patients--subclavian venous approach as the
      first choice.
AB  - BACKGROUND: It is critical to establish a safe and functional i.v. access in
      severely sick patients. We evaluated the frequency of application and
      complications of central venous catheters in a pediatric intensive care unit.
      METHODS: Pediatric patients in whom central venous catheters were inserted
      between March 1997 and May 1999 in the Pediatric Emergency Room and Intensive
      Care Unit were enrolled in this study. Patients were evaluated with respect to
      age, sex, weight, central venous catheter indication, site, duration of catheter
      stay and complications. RESULTS: During the study period a total of 156 central
      venous catheters were successfully inserted into 146 patients. Of the 156 central
      venous catheter attempts, 148 (94.9%) were placed into the subclavian vein, six
      were inserted into the femoral vein, and two into the jugular vein. In 156
      attempts, arterial injuries occurred in 20 cases (12.8%). Pneumothorax developed
      in two patients on mechanical ventilation. Three catheters had to be removed due
      to catheter related infections. The mortality rate was 0%. CONCLUSIONS: We
      concluded that subclavian central venous catheterization is a safe procedure with
      minimal complications in pediatric patients. Arterial injury was the most
      frequent complication. In experienced hands, the success rate was 100%.
      Subclavian central venous catheter insertion may be considered as the first
      approach in critically ill patients.

PMID- 11982879
TI  - Two cases of anaphylactic reaction to gelatin induced by a chloral hydrate
      suppository.

PMID- 11982880
TI  - Measles encephalitis: a report of two cases with variable manifestations.

PMID- 11982881
TI  - 11-year-old boy with sarcoidosis and generalized brawny induration of muscle.

PMID- 11982882
TI  - Failure of stent implantation in an infant with congenital tracheal stenosis.

PMID- 11982883
TI  - Megaloblastic anemia in an infant receiving total parenteral nutrition.

PMID- 11982884
TI  - Reactivation: a severe problem in familial hemophagocytic lymphohistiocytosis.

PMID- 11982885
TI  - Invasive food poisoning caused by Salmonella oranienburg.

PMID- 11982886
TI  - Case of CATCH 22 syndrome complicated with pseudohypoparathyroidism and
      unilateral renal aplasia.

PMID- 11982887
TI  - Acute renal failure in two infants due to ureteropelvic fungi balls.

PMID- 11982888
TI  - Prevention of respiratory syncytial virus infections in high-risk infants by
      monoclonal antibody (palivizumab).
AB  - Respiratory syncytial virus (RSV) is a major viral pathogen which causes serious
      respiratory illness in infants and children worldwide. Palivizumab (Synagis) is
      an anti-RSV monoclonal antibody administered intramuscularly for the prevention
      of severe RSV respiratory disease in high-risk infants and young children. The
      IMpact-RSV trial, the pivotal multicenter, randomized, placebo-controlled trial
      performed in the USA, Canada and the United Kingdom demonstrated an overall 55%
      reduction in hospitalization rate due to RSV infection in preterm infants (< or =
      35 weeks gestation) with and without chronic lung disease (CLD). Subgroup
      analysis in premature infants without CLD revealed an even greater reduction in
      RSV hospitalization rates (78%). Adverse events were infrequent and did not
      differ between placebo and palivizumab groups. Injection site reactions were
      infrequent and mild; no differences were observed between palivizumab and placebo
      subjects. Palivizumab does not interfere with administration of other pediatric
      vaccines. Comprehensive parent education programs regarding prevention of
      infection, avoidance of risk factors for infection, careful adherence to
      infection control policies, and recognition of early symptoms of RSV infection
      remain important components of RSV prevention strategies. In light of the lack of
      effective vaccines for this serious health risk, palivizumab offers the only
      option for prophylaxis against RSV disease in high-risk infants.

PMID- 11982889
TI  - Nitric oxide donor increases cerebral blood flow and oxygenation during kainic
      acid-induced seizures in newborn rabbits.
AB  - BACKGROUND: We investigated the hypothesis that sodium nitroprusside (SNP), a
      nitric oxide (NO) donor, increased the cerebral blood flow and oxygenation during
      kainic acid (KA)-induced seizures in newborn rabbits. METHODS: After KA
      administration (i.v. 12 mg/kg)to induce seizures, either 1.2 mg/kg SNP (SNP
      group, i.v., n = 6) or 1 mL normal saline (vehicle group, i.v., n = 6)was given.
      Regional cerebral blood flow (rCBF), cerebral oxyhemoglobin(oxy-Hb),
      deoxyhemoglobin (deoxy-Hb), total hemoglobin (t-Hb), mean arterial blood pressure
      (MABP), heart rate (HR) and electroencephalography(EEG) were continuously
      monitored throughout the experiment, lasting at least 60 min after the KA
      administration. RESULTS: The value for rCBF was greatly increased during seizures
      in the SNP group than in the vehicle group. The values for oxy-Hb and t-Hb were
      significantly increased, and deoxy-Hb was significantly decreased. There were
      ameliorations of cerebral oxygenation in the SNP group during the acute phase of
      seizures in the neonatal animals, compared with the vehicle group. There were no
      significant differences in the MABP, HR, arterial blood gases, rectal and brain
      temperatures, blood hemoglobin concentrations,blood glucose levels, the latencies
      to first abnormal discharges in EEG, the total sum of the duration of abnormal
      discharges in EEG and the incidences of subclinical electric status epileptics
      between the two groups. CONCLUSIONS: These results suggest that the treatment
      with SNP contributed to the increases in cerebral blood flow and oxygenation, and
      that EEG abnormalities were unchanged by the treatment with SNP during neonatal
      seizures.

PMID- 11982890
TI  - Bone mineral status in ambulatory pediatric patients on long-term anti-epileptic
      drug therapy.
AB  - BACKGROUND: For ambulatory pediatric outpatients,reports of abnormalities of bone
      metabolism associated with anti-epileptic drugs are inconsistent and may be
      difficult to interpret. METHODS: The effects of long-term anti-epileptic therapy
      (mainly valproic acid and/or carbamazepine) on bone mineral status were evaluated
      in ambulatory epileptic patients(seven males and 11 females) aged 5.5-15.9 years.
      Bone mineral density (BMD) at the lumbar spine was measured by dual-energy X-ray
      absorptiometry and markers of bone and mineral metabolism were determined.
      RESULTS: The mean BMD was decreased by 9% in our patients relative to the
      control, and five patients (all males)showed osteopenia, defined as BMD SD scores
      less than - 1.5. Serum levels of minerals, intact parathyroid hormone and
      1alpha,25(OH)2 vitamin D were within the normal ranges. In most patients, serum
      levels of intact osteocalcin, carboxyterminal propeptide of type I procollagen
      and pyridinoline cross-linked telopeptide of type I collagen were reduced
      relative to the corresponding mean control values. The BB genotype by BsmI
      restriction fragment length polymorphism, associated with low BMD, was not found
      in our patients. The dietary calcium intake in the osteopenic patients was
      significantly lower than that of the non-osteopenic patients. CONCLUSIONS: Our
      results indicate that long-term anti-epileptic treatment induces a state of
      decreased bone turnover in children, resulting in osteopenia preferentially in
      males. The alterations may be due, at least in part, to direct effects of the
      drugs on bone cells; and that low calcium intake could be an aggravating factor
      for anti-epileptic-associated osteopenia.

PMID- 11982891
TI  - Giant coronary aneurysms due to Kawasaki disease: a case-control study.
AB  - BACKGROUND: Epidemiologic features of giant coronary aneurysm due to Kawasaki
      disease and its risk factors are still not clear. METHODS: Sixty-six patients
      with giant coronary aneurysms were reported to a 15th nationwide survey of
      Kawasaki disease in Japan. With all other patients treated in the same hospital
      as a control group, odds ratios were calculated for certain potential risk
      factors. RESULTS: Infant males aged less than 1 year,neutrophil concentration
      among leukocyte, late administration of intravenous gammaglobulin (IVGG) therapy
      and additional administration of IVGGwere considered as risk factors of giant
      coronary aneurysms due to Kawasaki disease. In univariate analysis, use of IVGG
      therapy and a large amount of IVGG (2500+ mg/kg)elevated the risk, whereas the
      relationship disappeared after the adjustment. CONCLUSIONS: The observation of 66
      cases with giant coronary aneurysms due to Kawasaki disease reported to the
      nationwide survey provides some risk factors and consideration about the
      aneurysms.

PMID- 11982892
TI  - Cardiovascular effects of a phosphodiesterase III inhibitor, amrinone, in
      infants: non-invasive echocardiographic evaluation.
AB  - OBJECTIVE: The inotropic effect of amrinone is still controversial in management
      of congestive heart failure in pediatric patients, especially in infants. In
      order to determine the cardiovascular effect of amrinone in pediatric patients,
      we performed echocardiographic evaluation in 11 infants (mean age of 2 months)
      after intracardiac surgery. METHODS: Amrinone was loaded with a dose of 1.0
      mg/kg, followed by continuous infusion with 10 microg/kg per min. We performed
      echocardiographic measurements before and immediately after loading of amrinone,
      and evaluated its cardiovascular effect. RESULTS: After loading of amrinone, the
      heart rate increased by 5% in average, but there was no change in blood pressure.
      Left ventricular (LV) fractional shortening and mean velocity of circumferential
      fiber shortening corrected for heart rate increased significantly (0.25 +/- 0.09
      to 0.28 +/- 0.08 and 0.94 +/- 0.35 to 1.10 +/- 0.34, respectively). Left
      ventricular end-systolic wall stress decreased from 36.6 +/- 18.5 to 29.1 +/-
      14.4 g/cm2, indicating the reduction of LV afterload. Stress-velocity index, a
      sensitive index of left ventricular contractility, was elevated significantly (Z
      score: -1.45 +/- 4.21 to 0.04 +/- 4.11). CONCLUSION: Amrinone has not only
      vasodilative effects, but definite positive inotropic effects in infants with
      heart failure.

PMID- 11982893
TI  - Molecular analysis of syndromic congenital heart disease using short tandem
      repeat markers and semiquantitative polymerase chain reaction method.
AB  - BACKGROUND: Velo-cardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS) are
      developmental disorders characterized by craniofacial anomalies and conotruncal
      heart defects. Many of them have hemizygous deletions within chromosome 22q11.2,
      suggesting that haploinsufficiency in this region are responsible for their
      etiologies. METHODS: To effectively understand the molecular basis for the
      chromosomal deletions, a semiquantitative fluores-cent polymerase chain reaction
      (PCR) method using 11 highly polymorphic markers located in 22q11.2 to perform
      genotyping analysis on 10 probands (five VCFS and five DGS) and their unaffected
      relatives were designed. RESULTS: Two VCFS and four DGS patients have a 3-Mb
      deletion; the other DGS patient has a 1.5-Mb deletion and a cross-over occurs in
      the same interval at the other allele. CONCLUSION: This results supports that the
      specific regions in 22q11.2 are susceptible to rearrangement and the deletions
      might be the genetic etiology of these syndromes. Most important of all, the new
      method, semiquantitative fluorescent PCR, is an effective method for detecting
      chromosomal microdeletions and has the following features: (i) the cost is
      inexpensive; (ii) the testing time is short; and (iii) the result is accurate.

PMID- 11982894
TI  - Detection of neutrophil-associated immunoglobulin using flow cytometry in
      autoimmune neutropenia of infancy.
AB  - BACKGROUND: Autoimmune neutropenia of infancy (ANI) is a common form of chronic
      childhood neutropenia, which is caused by antineutrophil antibodies. The syndrome
      is characterized by a severe selective neutropenia accompanied with recurrent
      bacterial infections. METHODS: We investigated 10 ANI patients in our hospital.
      Neutropenia in ANI patients was found in patients aged between 9 and 19 months.
      They had no life-threatening infections and their infections episode could be
      controlled by the conventional antibiotic therapy in general. The correlation of
      absolute neutrophil counts (ANC) and neutrophil-associated immunoglobulin (NAIg)
      levels in each case was analyzed and their clinical courses followed. RESULTS:
      The NAIg levels were high in all cases at the diagnosis, however, they had no
      relationship with ANC. The severity of infection and the period of neutropenia in
      our patients have no correlation to NAIg levels either. In our four cases,
      neutropenia disappeared after a median of 26 months (range, 18-29 months). The
      periods of neutropenia were nearly similar to previous reports. After the NAIg
      level began to wane, neutrophil counts increased in four patients whose
      neutrophil counts had recovered finally. CONCLUSIONS: Detection of NAIg is useful
      for the diagnosis, and the observation of changes in NAIg may be helpful one by
      one for prediction of the prognosis.

PMID- 11982895
TI  - IgG and IgG subclasses deficiency in children undergoing continuous ambulatory
      peritoneal dialysis and its provocative factors.
AB  - BACKGROUND: Low levels of serum IgG or IgG subclasses may be responsible for the
      defective peritoneal defense and for peritonitis attacks in continuous ambulatory
      peritoneal dialysis (CAPD) children. Malnutrition, peritoneal loss or frequent
      peritonitis may lead to IgG or IgG subclasses deficiency. METHODS: Levels of IgG
      subclasses were determined in 12 children undergoing CAPD treatment. Radial
      immunodiffusion technique was used for determination. Patients were aged from 6
      to 16 years (mean age 12.3 years) and had been on CAPD for 11-26 months (mean
      duration 19.4 months). We evaluated whether IgG and IgG subclasses deficiency are
      related to malnutrition, the peritonitis rate and the duration of CAPD using the
      SPSS program. RESULTS: Serum total IgG levels were found to be low in eight out
      of 12 patients. Eight patients showed low levels of IgG1, four patients IgG2, one
      patient IgG3 and three patients IgG4. Total IgG values were found to be
      positively correlated to malnutrition status, peritonitis rate and duration of
      CAPD. The IgG2 values were found to be related to the duration of CAPD. The IgG4
      values were found to be correlated to the peritonitis rates. CONCLUSIONS: The IgG
      and IgG subclasses deficiency may develop in children while on CAPD treatment.
      Periodical determinations of either serum IgG or the subclasses may be useful in
      the follow-up of these patients.

PMID- 11982896
TI  - Helicobacter pylori infection in patients with idiopathic short stature.
AB  - BACKGROUND: Some investigators have recently described an association between
      Helicobacter pylori infection and children with short stature. In the present
      study, we aimed to evaluate children with short stature with different
      etiologies. METHODS: This study evaluated short patients aged from 1 to 16 years.
      These patients were divided into a growth hormone deficient short stature group
      (n = 27) and an idiopathic short stature group (n = 14). A control group included
      children with normal growth and no abdominal pain (n = 47). Anti-H. pylori
      antibodies were measured in each group (total of 88). RESULTS: The antibody
      positivity rates for each group were as follows: growth hormone deficient short
      stature group, 7.4%; idiopathic short stature group, 28.6%; and control group,
      6.4%. The H. pylori antibody positivity rate in the idiopathic short stature
      group was significantly higher than in the control group. CONCLUSION: Our
      findings suggest an association between H. pylori infection and idiopathic short
      stature.

PMID- 11982897
TI  - Human herpesvirus-6 infection in neonates: Not protected by only humoral
      immunity.
AB  - BACKGROUND: Infants are usually protected from various viral infections,
      including human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) infections,
      during the early infantile period by antibodies transferred from their mothers.
      However, rare cases of exanthem subitum (ES) in neonates have been described in
      published reports. METHODS: From the infantile patients of febrile illness, HHV-6
      and HHV-7 DNA were examined by the polymerase chain reaction method. Antibodies
      to HHV-6 and HHV-7 were detected by indirect immuno-fluorescence assay and
      neutralization test. Viral isolation was attempted from the patient's peripheral
      blood mononuclear cells (PBMC) during the acute phase of febrile illness.
      RESULTS: Human herpesvirus-6 was verified virologically in two neonates who were
      clinically diagnosed as ES within the first month of life. Although high copies
      of HHV-6 DNA were detected in their PBMC during the acute phase, the isolation of
      HHV-6 from their PBMC was not successful. Neutralizing antibodies to HHV-6 were
      detected in sera of the acute phase, and those antibodies were considered to be
      transferred from their mothers. Antibody titers showed fourfold elevation in sera
      of the convalescent phase. The HHV-6 infection occurred despite the presence of
      pre-existing maternal antibody. Human herpesvirus-7 and HHV-7 DNA were not
      detected from their clinical samples. CONCLUSIONS: This observation suggests that
      HHV-6 infection could not be protected by only humoral immunity.

PMID- 11982898
TI  - Serological levels of zinc, copper and iron elements among Giardia lamblia
      infected children in Turkey.
AB  - BACKGROUND: Giardiasis, an intestinal protozoan infection caused by Giardia
      lamblia, is common in Turkey, especially among children aged between 2- and 14
      years-old. Effects of giardiasis on serological levels of zinc, copper and iron
      elements were assessed in this study. METHODS: A total of 45 children, aged
      between 2- and 14-years-old, who were admitted to the Pediatrics Department of
      Celal Bayar University Medical School with gastrointestinal complaints and
      diagnosed as having giardiasis by stool examinations in the Parasitology
      Department, were enrolled as the study group (SG). The control group (CG)
      consisted of 45 age-matched healthy children. Serological levels of zinc, copper
      and iron were measured by atomic absorption spectrophotometer in all samples.
      RESULTS: As a result of the study, serum zinc levels were 67.43 +/- 17.72
      microg/dL and 145.20 +/- 9.13 microg/dL, copper levels were 198.45 +/- 39.14
      microg/dL and 150 +/- 21.14 microg/dL and iron levels were 87.98 +/- 18.31
      microg/dL and 160.45 +/- 45.40 microg/dL, in SG and CG, respectively. When
      compared separately as SG and CG, there was a statistically significant
      difference between the serological levels of all these elements. CONCLUSION:
      These results revealed that giardiasis increased the serological levels of
      copper, like other infectious agents. However, zinc and iron levels decreased
      during giardiasis due to malabsorption.

PMID- 11982899
TI  - Metabolic alkalosis with hypoelectrolytemia in infants with cystic fibrosis.
AB  - BACKGROUND: Infants with cystic fibrosis (CF) can develop episodes of
      hyponatremic hypochloremic dehydration with metabolic alkalosis when they sweat
      excessively, which is not caused by sweating in normal infants. We investigated
      the incidence of the metabolic alkalosis with hypoelectrolytemia in CF infants,
      the possible risk factors for its occurrence and the importance of the
      manifestation in the diagnosis of CF. METHODS: In order to evaluate the incidence
      and the risk factors for the development of this sweat-related metabolic disorder
      in CF, we reviewed the records of all children diagnosed as having CF before the
      age of 12 months in a 10-year period. Data analysis included medical history
      data, clinical features, biochemical parameters (blood pH, serum bicarbonate,
      sodium, chloride and potassium levels), sweat chloride test values, as well as
      genetic analysis data. RESULTS: The prevalence of metabolic alkalosis in
      association with low serum electrolyte concentrations (hyponatremia,
      hypochloremia, and hypokalemia) in infant CF population in our region was 16.5%.
      We found no season predilection in its occurrence. Early infant age, breast
      feeding, delayed CF diagnosis, heat exhaustion and the presence of severe CF
      transmembrane conductance regulator mutations are predisposed factors for the
      development of metabolic alkalosis with hypoelectrolytemia. CONCLUSIONS: The
      results from our study suggest that metabolic alkalosis with hypoelectrolytemia
      is a relatively common manifestation of CF in infancy. The possibility of CF
      should be seriously considered in any infant with this metabolic disorder.

PMID- 11982900
TI  - Low plasma levels of hemostatic proteins during the induction phase in children
      with acute lymphoblastic leukemia: A retrospective study by the JACLS. Japan
      Association of Childhood Leukemia Study.
AB  - BACKGROUND: Thromboembolic and bleeding events are serious complications
      associated with the administration of L-asparaginase (ASP) during the induction
      phase in children with acute lymphoblastic leukemia (ALL). Prophylactic
      supplementation of plasma-derived coagulation products remains controversial. The
      purposes of this study were to examine the plasma levels of hemostatic proteins
      during the induction phase and the efficacy of prophylactic replacement of plasma
      derived products. METHODS: A multicenter retrospective survey on the incidence of
      hemostatic complications and the frequency of prophylactic replacement of plasma
      derived products among children with ALL who under went ASP therapy was
      conducted. All patients were treated according to the Japan Association of
      Childhood Leukemia Study (JACLS) ALL-97 protocol. RESULTS: Thirty-six (67%) of
      the 54 JACLS-treatment centers responded and provided information on 127
      patients. Clinically relevant hemostatic complications occurred in two patients
      (1.6%;2/127); one patient suffered intracranial bleeding 5 days after beginning
      the protocol, and the second patient suffered an ischemic attack during an ASP
      treatment. The administration of ASP(10 000 u/m2 x six doses) led to significant
      reductions in the plasma fibrinogen (180 +/- 74 to 105 +/- 57 mg/dL),antithrombin
      III (AT III) (126 +/- 21 to 73 +/- 18%),and plasminogen levels (97 +/- 17 to 52
      +/- 18%). These laboratory parameters returned to normal levels 2 weeks after
      completion of the ASP treatment. Forty-eight patients (38%)received AT III
      concentrate (AT III-supplement group). The AT III level of the AT III-supplement
      group was significantly lower than that of the AT III non-supplement group, not
      only during the ASP therapy, but also prior to the ASP therapy. A greater
      percentage of patients in the AT III-supplement group received fresh-frozen
      plasma and in greater amounts than those in the AT III non-supplement group.
      CONCLUSIONS: Severe hemorrhage and thrombosis were uncommon in the ALL patients
      who underwent ASP therapy in comparison with the degree of coagulation changes.
      Prophylactic administration of AT III concentrate or fresh-frozen plasma did not
      demonstrate clear beneficial effects in the treatment of ALL in preventing
      thromboembolic events.

PMID- 11982901
TI  - High-dose chemotherapy in children with metastatic hepatoblastoma.
AB  - BACKGROUND: Despite the advent of effective chemotherapy,a poor prognosis has
      been reported for patients with metastatic hepatoblastoma. To improve this
      prognosis, we conducted high-dose chemotherapy with autologous bone marrow rescue
      in patients with metastatic hepatoblastoma. METHODS AND RESULTS: Three patients
      were treated with high-dose chemotherapy. In patient 1, high-dose chemotherapy
      was given after the patient's first pulmonary relapse. Additional pulmonary
      metastases, which developed more than 6 months after high-dose chemotherapy, were
      treated by multiple thoracotomy without additional chemotherapy. Patient 2
      presented additional pulmonary metastases soon after the end of the first
      thoracotomy and high-dose chemotherapy. Because of a decreased serum alpha
      fetoprotein level after re-excision of the pulmonary metastases, a second round
      of high-dose chemotherapy was performed. In patient 3, multiple pulmonary
      metasteses responded to preoperative chemotherapy and disappeared according to
      the chest computed tomography. Intensive treatment with a high-dose
      chemotherapeutic regimen was performed at the end of postoperative chemotherapy.
      All three patients are alive and well, more than 6 years after receiving their
      diagnosis. CONCLUSION: The role of high-dose chemotherapy in treatment of
      metastatic hepatoblastoma could not be clarified,because of the small number of
      patients. However, the better outcome of our patients indicates that multimodal
      therapy, including high-dose chemotherapy, may improve the outcome of the
      patients with metastatic hepatoblastoma.

PMID- 11982902
TI  - Tracheostomy in childhood: 20 years experience from a pediatric surgery clinic.
AB  - BACKGROUND: There is a limited indication for tracheostomy procedures in
      pediatric surgery. It is rarely applied to the pediatric patient because they can
      be kept intubated for a longer duration compared with adults. Problems and
      complications can occur after tracheostomy, even during the childhood period.
      PURPOSE: The purpose of this study is to evaluate our experience with
      tracheostomy procedure. METHODS: Records of 17 children treated over a 20-year
      period (1978-99) were reviewed retrospectively in the aspects of indication,
      complication and mortality. RESULTS: There were 13 boys and four girls with a
      mean age 30.3 months (range: 1 week-13 years). Indications for tracheostomy were
      prolonged intubation (n = 5), subglottic stenosis (n = 3), general body trauma (n
      = 2), tracheomalasia (n = 2), tracheoesophageal cleft (n = 1), cervical tumor
      pressing trachea and larynx (n = 1), congenital myotonic dystrophy plus
      respiratory failure (n = 1), burn injury of trachea and esophagus (n = 1), and
      foreign body aspiration (n = 1). In the last decade the number of cases with
      tracheotomy increased due to the development of new intensive care units, the use
      of mechanical ventilation and the increasing number of patients needing prolonged
      ventilation support. In this group, tracheostomies were mainly performed
      electively. The overall complication rate was 29%. Mortality was 59% and there
      was one death related to the tracheostomy procedure. CONCLUSION: Tracheostomy is
      a life saving procedure when performed with an appropriate indication and
      surgical technique. Therefore, the pediatric surgeons dealing with this procedure
      should be aware of the tracheostomy care problems, fatal complications and the
      need for reconstructive surgery. With strict indications and experience of the
      procedure, this should be enough effort to minimize its complications and related
      care problems.

PMID- 11982903
TI  - Tachycardia-induced left ventricular dysfunction in children.

PMID- 11982904
TI  - Complete cleft sternum and congenital heart disease: review of the literature.

PMID- 11982905
TI  - Coil closure of a large patent arterial duct in a low-birthweight infant.

PMID- 11982906
TI  - Thin basement membrane disease with membranoproliferative glomerulonephritis in a
      13-year-old girl.

PMID- 11982907
TI  - Detection of Helicobacter pylori-associated asymptomatic duodenal ulcer in a boy.

PMID- 11982908
TI  - Hyperimmunoglobulinemia D syndrome successfully treated with a corticosteroid.

PMID- 11982909
TI  - Pericentric inversion inv(2) (p11.2q21) associated with Treacher Collins
      Franceschetti syndrome.

PMID- 11982910
TI  - Gonadal sex cord stromal tumor in a patient with Rubinstein-Taybi syndrome.

PMID- 11982911
TI  - Novel missense mutation in the purine nucleoside phosphorylase gene in a Japanese
      patient with purine nucleoside phosphorylase deficiency.

PMID- 11982912
TI  - Management of childhood diseases in the Byzantine period: I -- analgesia.
AB  - Evidence on the use of pain relievers for medical purposes in childhood was
      traced in medical treatises during Byzantine times (4th to 15th century ad). The
      texts of Aetius, Paulus Aeginitis, Orivasios and others strongly reveal
      influences from ancient Greek medicine. Greek physicians of the times, who helped
      the medical thinking of antiquity to stay alive, used opium with mandragoras,
      hyoscyamos and other sedative herbs to produce a kind of anesthetic state and to
      relieve pain. However, in children's cases they chose to selectively use
      substances in more standardized quantities, mainly in mixtures. Less aggressive
      methods such as warm baths, or appropriate food were highly respected by them and
      recommended for the treatment of sick children.

PMID- 11982913
TI  - Management of childhood diseases in the Byzantine period: II - exanthematic
      diseases.
AB  - The aim of this review was to explore the procedures used for the treatment of
      childhood exanthematic diseases during the Byzantine period. The most often
      reported ones were psoriasis, undefined rashes in parts of the body, ulcerous
      rashes, blisters, lichens and soaked ulcers. The physicians of the period managed
      the above problems with appropriate diet and remedies of herbal, veterinary and
      chemical origin in the form of baths, poultices and concoctions. They largely
      based their principles on the ancient Greek medical tradition. Their accurate
      remarks were reflected in their terminology. Many of the terms of this period are
      still in use, although current treatment modalities are quite different from the
      Byzantine remedies.

PMID- 11982914
TI  - Children Behavior Checklist (CBCL)/2-3 in children with febrile episodes under 3
      months of age and enterovirus infection.

PMID- 11982915
TI  - An update on photoprotection.

PMID- 11982916
TI  - Genomic scale analysis of the human keratinocyte response to broad-band
      ultraviolet-B irradiation.
AB  - Ultraviolet B (UVB) radiation is an important inducer of many biologic changes in
      skin, of which keratinocytes are a key target. To gain better insight into
      changes in gene expression generated in the early phase after UVB exposure, we
      used complementary RNA (cRNA) microarray hybridization to compare differences in
      mRNA expression of UVB-irradiated (single dose of 100 J/m2 broad-band UVB) and
      sham-irradiated primary cultured human keratinocytes. Six hours after
      irradiation, total RNA was isolated from keratinocytes, and cRNA was synthesized
      and hybridized to a GeneChip expression array (Affymetrix) consisting of 6800
      genes. Based on a threshold of > twofold change, 187 genes (2.8%) were designated
      to be the most UVB-responsive. Surprisingly, none of these genes had been shown
      previously to be modulated by UVB. Conversely, several genes in the microarray
      that had been reported previously to be UVB- responsive by other methods showed
      less (< twofold) or no change. Northern blotting of seven differentially
      modulated genes produced results similar to those derived from microarray
      technology, thereby validating the accuracy of screening. Clustering based on
      known or likely functions indicated that among 88 upregulated genes, nine encode
      for cytochrome c subunits, six for ribosomal proteins, and two for regulators of
      apoptosis. By contrast, many of the 99 downregulated genes are involved in
      transcription, differentiation and transport. These findings indicate that
      keratinocytes respond to a single low dose of broad-band UVB irradiation by
      enhancing processes involved in energy production and translation, while
      suppressing those related to transcription, differentiation and transport.

PMID- 11982917
TI  - In vivo measurement of the photostability of sunscreen products using diffuse
      reflectance spectroscopy.
AB  - BACKGROUND/AIM: The issue of the photostability of sunscreens has been frequently
      raised because of the possible loss of photoprotection, mainly in the UVA range,
      during sun exposure. Up to now, in vitro techniques have been mainly proposed to
      evaluate photostability. These techniques have generated controversial debates
      concerning the predictive value of these in vitro observations in relation to the
      in vivo reality during sun exposure. METHODS: Diffuse reflectance spectroscopy
      (DRS) is a recently developed technique that allows measurement of the UVA
      efficacy of sunscreen products in vivo on human volunteers. The absorption
      spectrum of the product is obtained by measuring the change in reflection of the
      skin with and without product. From this absorption spectrum, the UVA protective
      efficacy of the test product can be calculated for an appropriate source and a
      given biological action spectrum. We have used the DRS technique in vivo to
      determine the photostability of sunscreen products by measuring reflection
      spectra in the UVA range (320-400 nm) before and after product application and
      before and after UV exposure of the test products. Comparison between these
      spectra or between the corresponding calculated UVA protection factors has made
      it possible to determine the remaining level of protection in the UVA range after
      exposure. This study was designed to compare in vivo the protective efficiency
      and the photostability of three marketed sunscreen products (SPF 23-30) after
      solar-simulated exposure for SPF testing or after actual sun exposure. These in
      vivo data were then compared to in vitro photoinstability results. RESULTS:
      According to the in vitro measurements, one sunscreen product was found
      photostable and two products photo-unstable. After UVe exposure for in vivo SPF
      determination, a decrease in UVA absorption and UVA-PF was observed for the two
      photo-unstable products, while the photostable product did not present any
      decrease in UVA absorption. These results were confirmed through exposure to
      actual sun. CONCLUSION: Our study confirms the prediction of the in vitro methods
      previously used to assess the photostability of sunscreen products. In addition,
      DRS provides a powerful new tool for the in vivo simultaneous evaluation of
      photostability and estimation of the UVA protection factor of sunscreen products
      performed during the test for SPF determination.

PMID- 11982918
TI  - Time course of ultraviolet-induced skin reactions evaluated by two different
      reflectance spectrophotometers: DermaSpectrophotometer and Minolta
      spectrophotometer CM-2002.
AB  - BACKGROUND: Many attempts have been made to quantify ultraviolet (UV)-induced
      erythema and pigmentation, but most studies have been focused on the initial
      changes of reaction for a few hours or days and neglected the later events.
      METHODS: : A time course of skin colour changes induced by fluorescent sunlamp
      with a broad band of UVA and UVB radiation was evaluated in 15 Korean male
      volunteers using two different reflectance spectrophotometers for 28 days. The
      results were presented by E (erythema)- and M (melanin)-index as well as values
      converted to the L*a*b* system recommended by the CIE (Commission Internationale
      de l'Eclairage). RESULTS: The mean individual typology angle of the subjects was
      46.6 degrees, which indicated "light" group in constitutional skin colour
      category. A day after UV exposure, the L* and b* values decreased significantly,
      following the colour direction of persistent pigment darkening. The values went
      in the opposite direction persistently until after the 1st week, when maximum
      tanning was obtained. They then shifted toward their original positions, parallel
      to the constitutive melanization axis. The a* index showed a significant increase
      toward the mean colour of haemoglobin on day 1. It returned to its original value
      along the constitutive melanization axis. The E-index showed a maximum value at
      day 1, then returned to baseline. The value of M-index reached a peak at day 7.
      There was no significant difference between the two instruments, but each has its
      own characteristic features. CONCLUSION: These promising quantitative methods
      should enable us to achieve objective measurement of the dermatophysiologic
      changes and to evaluate the efficacy of therapeutic modalities on skin disorders
      without the inherent errors associated with subjective judgement. Our results
      provide standard data on a time course of UV-induced skin erythema and
      pigmentation.

PMID- 11982919
TI  - Influence of wetness on the ultraviolet protection factor (UPF) of textiles: in
      vitro and in vivo measurements.
AB  - BACKGROUND/PURPOSE: Clothing is an important product for sunburn protection and
      skin cancer prevention. The moisture content of a fabric, which can increase
      during its wearing, may decrease the fabric's capability of protecting the skin
      from solar UV radiation, that is, lower its UPF (ultraviolet protection factor).
      Due to limited data about the effect of fabric wetness on UPF, this study was
      undertaken to investigate the following: (a) the effect of saturating a variety
      of fabrics with tap water and with salt water on fabric UPF and (b) whether
      wetted-fabric UPF values reflect only the fact that the fabric is wet during
      testing or the fact that the skin is hydrated and the fabric is wet. METHODS: For
      objective a, 69 summer fabrics were spectrophotometrically (in vitro) assessed
      when "dry" and when saturated with tap and salt water. In vitro UPFs, percent UVA
      transmission and percent UVB transmission values were calculated from the
      transmission data. For objective b, 100% cotton and 100% polyester fabrics were
      tested in vivo to determine in vivo UPF values. The minimal erythema dose (MED)
      was determined for each of the 12 subjects on unprotected "dry" skin and on
      "hydrated" unprotected skin. MEDprotected was determined when the subject's skin
      was covered with "dry" and with saturated fabric. In vivo UPFs were calculated
      using this data. Student's paired t-tests were used to determine the effect of
      wetting. RESULTS: With one exception, in vitro UPF values were the same when the
      fabrics were saturated with tap water and when they were saturated with salt
      water. However, saturating the fabrics with water had different effects on the
      UPF, UVA transmission, and UVB transmission values. For linen, viscose and
      polyester fabrics, UPF significantly increased. For the cotton fabrics and the
      polyester + TiO2 fabrics, UPF significantly decreased. For the modal + TiO2
      fabrics and the polyester crepe + TiO2 fabrics, UPF significantly increased. From
      the in vivo testing, the MED of the "hydrated unprotected" skin was not different
      than the MED of "dry unprotected skin." Values obtained from subtracting dry
      fabric in vivo UPF values from dry-fabric in vitro values and subtracting wet
      fabric in vivo UPF values from wet-fabric in vitro values are not different.
      CONCLUSION: Fabrics do not need to be tested when saturated with tap and with
      salt water. Testing fabrics wet and dry should be done, as the effect of
      saturating fabric on UPF value varies. Fortunately, UPF values for wetted fabrics
      reveal only the effect of increased moisture content in the fabric and have
      nothing to do with wetting of the skin by the fabric.

PMID- 11982920
TI  - Extracorporeal photochemotherapy for secondary chronic progressive multiple
      sclerosis: a pilot study.
AB  - BACKGROUND/PURPOSE: Extracorporeal photochemotherapy (ECP) has been proposed for
      the treatment of various auto- and allo-immune reactions. However, a standard ECP
      regimen did not significantly alter the course of chronic progressive multiple
      sclerosis (MS). We tested whether an intensive ECP treatment can affect the
      course of secondary chronic progressive form of MS. METHODS: Five patients free
      of immunosuppression were included. Soluble 8-MOP was added ex vivo to a
      mononuclear cell suspension obtained in a cell separator. This cellular
      suspension was then irradiated using an UVA irradiator and re-infused into the
      patient. ECP was performed once a week for 6 weeks and then, depending on
      clinical evaluation, for a maximum of 6 months, with 2-year follow-up after
      treatment discontinuation. Scoring was performed with the Kurzke scale and EDSS
      by a single independent neurologist. RESULTS: One patient was excluded because of
      recurrent attacks at the very beginning of treatment. Four patients completed the
      study: one exhibited clinical improvement and three remained stable during the
      first 6 months of treatment. However, all experienced relapse or worsening of the
      disease after discontinuation of ECP treatment. CONCLUSION: Our intensive ECP
      treatment only transiently alters the course of the severe secondary chronic
      progressive form of MS, with rebound after treatment discontinuation.

PMID- 11982921
TI  - What is the role of narrowband UVB in the treatment of psoriasis?

PMID- 11982922
TI  - Should we switch from combination UVA/UVB phototherapy units to narrowband UVB?

PMID- 11982925
TI  - What's new in photoimmunology?

PMID- 11982926
TI  - Allergic and photoallergic contact dermatitis to Olaquindox in a pig breeder with
      prolonged photosensitivity.

PMID- 11982927
TI  - All papers published from 1990 are now electronically available as pdf files.

PMID- 11982928
TI  - Association of alpha-amylase and the R1 protein with starch granules precedes the
      initiation of net starch degradation in turions of Spirodela polyrhiza.
AB  - In turions of Spirodela polyrhiza (L.) Schleiden, net degradation of storage
      starch is controlled by a special low fluence response of phytochrome requiring
      illumination for several days. This light effect has been used to study protein
      starch interactions that occur prior to and during net degradation of starch.
      Following various pretreatments on S. polyrhiza turions, native starch granules
      were isolated and two fractions of starch-related proteins were distinguished:
      proteins enclosed within the starch particles (starch-internalized proteins) and
      those attached to the surface (starch-associated proteins). The pattern of starch
      associated proteins as resolved by SDS-PAGE was more complex than that of starch
      internalized proteins and varied depending upon the pretreatment of the turions.
      Two starch associated proteins were identified immunochemically as alpha-amylase
      (EC 3.2.1.1) and the R1 protein (Lorberth et al. (1998) Nature Biotechnology 16:
      473-477). Dark-pretreatment of non-dormant turions does not induce starch net
      degradation. Under these conditions, alpha-amylase and R1 were bound to the
      surface of the starch granules. Continuous illumination with red light induces a
      rapid degradation of starch. Within the first 24 h of illumination the level of
      starch-associated alpha-amylase transiently increased and subsequently decreased
      rapidly. Similarly, the amount of the starch-associated R1 also decreased during
      illumination. The dissociation of both alpha-amylase and R1 from the starch
      granules preceded the decrease in starch content. However, binding of the two
      proteins to starch granules remained unchanged when the turions did not perform
      net starch degradation (as observed during continuous darkness, orthophosphate
      deficiency, or dormancy of the turions). Thus, during net starch degradation, so
      far unidentified changes are postulated to occur at the surface of the starch
      particles that are relevant for protein binding. This conclusion was supported by
      in vitro studies in which the binding of purified beta-amylase (EC 3.2.1.2) to
      starch granules isolated from turions following various pretreatments was
      monitored. The enzyme did bind to starch granules prepared from dark-stored
      turions (in which starch degradation had not been initiated), but not to those
      isolated from illuminated (starch degrading) turions.

PMID- 11982929
TI  - Temperature and oxygen regulation of oleate desaturation in developing sunflower
      (Helianthus annuus) seeds.
AB  - The effect of low (10 degrees C) and high (30 degrees C) temperature on in vivo
      oleate desaturation has been studied in developing sunflower (Helianthus annuus
      L.) seeds under conditions of different oxygen availability (capitulum, detached
      achenes or peeled seeds). In seeds remaining in the capitulum, only a part of the
      oleate newly synthesized at high temperature was desaturated to linoleate,
      whereas more oleate than that synthesized de novo was desaturated at low
      temperature. Achenes were only able to significantly desaturate oleate at low
      temperatures. In contrast, oleate desaturation was detected in peeled seeds
      incubated at low and high temperatures, showing the highest rate at 20 degrees C.
      Hull removing dramatically increased the activity of the microsomal oleate
      desaturase (FAD2, EC 1.3.1.35) at all studied temperatures, although a long-term
      inactivation of the enzyme was observed at high temperatures. Low oxygen
      concentration (1-2%) obtained by respiration of peeled seeds incubated in sealed
      vials, brought about the inactivation of the enzyme. All these data suggest that
      temperature regulates oleate desaturation controlling the amount of oleate and
      the FAD2 activity. In addition, this enzyme seems to be also regulated by the
      availability of oxygen, which is affected inside the achene by its diffusion
      through the hull, and the competition with respiration, both factors being
      temperature-dependent.

PMID- 11982930
TI  - Changes in the phosphorylation state of sucrose synthase during development of
      Japanese pear fruit.
AB  - Changes in the protein level and phosphorylation state of sucrose synthase (SS)
      were studied throughout the development of Japanese pear fruit. The level of SS
      protein was high at the young stage, dropped with fruit enlargement and increased
      again with fruit maturation. Antibody against phospho-Ser reacted with SS from
      young fruit, but did not react with SS that had been dephosphorylated by alkaline
      phosphatase (AP). The activities of SS isozymes were separated by ion-exchange
      chromatography. It was found that the fluctuation in SS activity was caused by
      two SS isozymes (SSI and SSII); (SSI reacted with antibody against phospho-Ser,
      while SSII did not. Phosphorylation of SS affected its kinetic parameters, that
      is, the affinity of phosphorylated SS for UDP was higher than that of
      dephosphorylated SS, while it was the contrary for UDP-glucose. The reaction of
      dephosphorylated SS was inclined toward sucrose synthesis more than that of
      phosphorylated SS. Phosphorylated SS protein was most abundant in young fruit,
      but decreased with fruit development, while non-phosphorylated SS protein
      increased in mature fruit. These results suggest that SS isoforms may be affected
      by post-translational modifications such as phosphorylation, and that the
      regulation of phosphorylation may potentially control the properties and
      functions of SS throughout the development of Japanese pear fruit.

PMID- 11982931
TI  - Relationship between bacteroid poly-beta-hydroxybutyrate accumulation and nodule
      functioning in the Galega orientalis-Rhizobium galegae symbiosis under diamine
      treatment.
AB  - Exposure of Galega orientalis plants to diamines putrescine (Put) and cadaverine
      (Cad) at concentrations from 0.01 to 2.0 mM significantly altered carbon and
      nitrogen metabolism in their root nodules. Correlative studies of bacteroid poly
      beta-hydroxybutyrate (PHB) content and acetylene-reduction capacity of the
      nodules revealed a negative relationship between these parameters. Utilisation of
      PHB deposits by bacteroids and high acetylene reduction activity was observed
      when applying low diamine concentrations. The increase in PHB accumulation in
      response to high diamine levels was accompanied by a considerable decline in
      nodule nitrogenase activity. Supplying isolated Galega bacteroids with various
      diamine concentrations significantly modified bacteroid oxygen consumption, which
      might be associated with alterations in carbon flux to the bacteroids. Finally,
      modulation of the bacteroid content upon Put and Cad treatment was examined. The
      results are discussed in terms of possible causes of the diamine-induced changes
      in nodule metabolism.

PMID- 11982932
TI  - In situ characterization of a NO-sensitive peroxidase in the lignifying xylem of
      Zinnia elegans.
AB  - The lignifying xylem from Zinnia elegans stems gives an intense reaction with
      3,3',5,5'-tetramethylbenzidine (TMB), a reagent previously reported to be
      specific for peroxidase/H2O2. However, the staining of lignifying xylem cells
      with TMB is apparently the result of two independent mechanisms: one, the
      catalase-sensitive (H2O2-dependent) peroxidase-mediated oxidation of TMB, and the
      other, the catalase-insensitive oxidation of TMB, probably mediated by xylem
      oxidases which are specific from lignifying tissues. The catalase-insensitive
      oxidation of TMB by the Z. elegans xylem was sensitive to sodium nitroprusside
      (SNP), a nitric oxide (NO)-releasing compound that, when used at 5.0 mM, is
      capable of sustaining NO concentrations of 6.1 &mgr;M in the aqueous phase. This
      effect of SNP was totally reversed by 150 &mgr;M 2-phenyl-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxide (PTIO), an efficient NO scavenger in biological
      systems, so the above-mentioned effect must be ascribed to NO, and not to other
      nitrogen oxides. This response of the catalase-insensitive TMB-oxidase activity
      of the lignifying Z. elegans xylem was similar to that shown by a basic
      peroxidase isolated from the intercellular washing fluid, which showed TMB
      oxidase activity, and which was also inhibited by 5 mM SNP, the effect of SNP
      also being reversed by 150 &mgr;M PTIO. These results suggest that peroxidase was
      the enzyme responsible for the NO-sensitive catalase-insensitive TMB-oxidase
      activity of the lignifying Z. elegans xylem. Further support for this statement
      was obtained from competitive inhibitor-dissected histochemistry, which showed
      that this stain responded to peroxidase-selective competitive inhibitors, such as
      ferulic acid and ferrocyanide, in a similar way to the Z. elegans basic
      peroxidase. From these results, we conclude that this NO-sensitive catalase
      insensitive oxidation of TMB is apparently performed by the Z. elegans basic
      peroxidase, and that the regulation of this enzyme by NO may constitute an
      intrinsically programmed event during the differentiation and death of the xylem.

PMID- 11982933
TI  - Expression of asparagine synthetase in rice (Oryza sativa) roots in response to
      nitrogen.
AB  - The expression of asparagine synthetase (AS; EC 6.3.5.4) in response to
      externally supplied nitrogen was investigated with respect to enzyme activity and
      protein levels as detected immunologically in rice (Oryza sativa) seedlings. The
      asparagine content was very low in leaves and roots of nitrogen-starved rice
      plants but increased significantly after the supply of 1 mM NH4+ to the nutrient
      solution. While neither AS activity nor AS protein could be detected in leaves
      and roots prior to the supply of nitrogen, levels became detectable in roots but
      not in leaves within 12 h of the supply of 1 mM NH4+ or 10 mM glutamine. Other
      nitrogen compounds, such as nitrate, glutamate, aspartate and asparagine had no
      effect. Methionine sulfoximine completely inhibited the NH4+-induced accumulation
      of AS protein but did not affect the glutamine-induced accumulation of the
      enzyme. The results suggested that glutamine or glutamine-derived metabolites
      regulate AS expression in rice roots.

PMID- 11982934
TI  - Kinetics of net H+, Ca2+, K+, Na+, NH+4, and Cl- fluxes associated with post
      chilling recovery of plasma membrane transporters in Zea mays leaf and root
      tissues.
AB  - Although temperature-induced changes in membrane structure and activity seem to
      be central to chilling stress perception, the specific details of temperature
      effects on plant nutrient acquisition remain obscure. In this study, we have
      undertaken a comparative study of low temperature effects on the activity of
      plasma membrane transporters of different ions in corn (Zea mays L.) leaf and
      root tissues by non-invasive measurements of net ion fluxes using ion-selective
      microelectrode (the MIFE) technique. Kinetics of net H+, Ca2+, K+, Na+, NH+4 and
      Cl- fluxes were measured as plant tissues recovered after short-term (3 h)
      chilling stress. The major findings can be summarized as follows: (1) The
      critical temperatures, under which the recovery of the activity of plasma
      membrane transporters took place, were found to be the same for all ions measured
      and are likely to be associated with the phase transition of membrane lipids. (2)
      The most pronounced was the reduction in net uptake of K+ and NH+4 (3) Chilling
      treatment caused a significant net influx of Cl- and Na+ in the leaf tissue. (4)
      For the same species, the critical temperatures for membrane-transport processes
      in roots were 2-2.5 degrees C lower than in leaves. Possible physiological
      significance of these findings is discussed.

PMID- 11982935
TI  - Does the direct effect of atmospheric CO2 concentration on leaf respiration vary
      with temperature? Responses in two species of Plantago that differ in relative
      growth rate.
AB  - The objective of this study was to investigate the direct effect of elevated
      atmospheric CO2 concentrations on leaf respiration in darkness (R) over a broad
      range of measurement temperatures. Our aim was to further elucidate the
      underlying mechanism(s) of the often-reported inhibition of leaf R by a doubling
      of the atmospheric CO2 concentration. Experiments were conducted using two
      species of Plantago that differed in maximum relative growth rate (fast-growing
      Plantago lanceolata L. and the slow-growing P. euryphylla Briggs, Carolin &
      Pulley). Rates of leaf respiration (R) were measured at atmospheric CO2
      concentrations ranging from 75 to 2000 &mgr;mol mol-1 at temperatures from 12 to
      42 degrees C. R was measured as CO2 release with a portable gas exchange system
      with infrared gas analysers. Our hypothesis was that the changes in temperature
      alter the flux coefficient (i.e. the extent to which changes in potential enzyme
      activity has an effect on the rate of a reaction) of enzymes potentially affected
      by CO2. Initial analysis of our results suggested that R was inhibited by
      elevated CO2 in both species, with the apparent degree of inhibition being
      greatest at low temperature. Moreover, the apparent degree of inhibition
      following a doubling of atmospheric CO2 concentration from 350 to 700 &mgr;mol
      mol-1 was similar to that reported by several previous studies (approximately 14%
      and 26% for P. lanceolata and P. euryphylla, respectively) at a temperature equal
      to the mean of the previous studies. However, subsequent correction for diffusion
      leaks of CO2 across the gas exchange's cuvette gaskets revealed that no
      significant inhibition had occurred in either species, at any temperature. The
      inhibitory effect of elevated CO2 on leaf respiratory CO2 release reported by
      previous studies may therefore have been overestimated.

PMID- 11982936
TI  - Nitrate reductase from winter wheat leaves is activated at low temperature via
      protein dephosphorylation.
AB  - The effect of short-term low temperature treatment on nitrate reductase (NR, EC
      1.6.6.1) activity, NR protein and NR transcript levels in excised leaves of
      winter wheat (Triticum aestivum L. cv. Sadovo-1) was investigated. NR activity,
      measured in the presence of Mg2+ (NRact), doubled within 2 h at 4 degrees C,
      whereas NR activity, measured in the presence of EDTA (NRmax), did not respond to
      the cold treatment. Such an activation of NR occurred only if leaves were exposed
      to low temperature in the light but not in the dark. It was not affected by
      feeding cytoplasmic protein synthesis inhibitor, cycloheximide, or protein kinase
      inhibitor, staurosporin, but was completely prevented by okadaic acid, an
      inhibitor of protein phosphatases of the type 1 and 2 A. This inhibitory effect
      decreased gradually when okadaic acid-concentration in the nutrient solution was
      lowered below 1 &mgr;M and tended to disappear when leaves were fed with 10 nM
      okadaic acid. It was demonstrated that the cold-induced NR activation was
      dependent neither on cold-triggered calcium influx nor on high endogenous
      abscisic acid levels. The increased NRact in cold-exposed leaves was found to
      correlate with a higher level of NR transcript but not with an increased NR
      protein level. Feeding okadaic acid to these leaves prevented the cold-induced
      accumulation of NR mRNA. These data point to protein phosphatases of the type 2 A
      being involved in NR protein dephosphorylation and NR transcript accumulation as
      targets of activation by low temperature treatment.

PMID- 11982937
TI  - Involvement of putative chemical wound signals in the induction of phenolic
      metabolism in wounded lettuce.
AB  - Cutting leaves of Romaine lettuce (Lactuca sativa L. cv. Longifolia) produces a
      wound signal that induces the synthesis of phenylalanine ammonia lyase (PAL, EC
      4.3.1.5) and the accumulation of phenolic compounds in cells up to 2 cm from the
      site of injury, and tissue browning near the site of injury. The response of
      leaves within a head of Romaine lettuce to putative chemical wound signals
      [abscisic acid (ABA), jasmonate (JA) and methyl jasmonate (MeJA)] differed
      significantly with leaf age. Exposure of harvested heads of lettuce to ABA, JA,
      MeJA, or salicylic acid (SA) did not induce changes in PAL activity, the
      concentration of phenolic compounds or browning in mature leaf tissue that was
      similar to the level induced by wounding. Methyl jasmonate applied as vapour (10,
      100 or 1000 &mgr;l kg-1 FW), or as an aqueous spray or dip (0.01-100 &mgr;M) at 5
      or 10 degrees C did not produce an effect on PAL activity or browning that
      differed significantly from the untreated controls. In contrast, JA, MeJA and SA
      did induce elevated levels of PAL activity in younger leaves. However, the levels
      induced were far lower than those induced by wounding. Wound induced phenolic
      metabolism in mature leaves appears to be induced by different signals than those
      functioning in young leaves.

PMID- 11982938
TI  - Local and differential control of vegetative storage protein expression in
      response to herbivore damage in Arabidopsis thaliana.
AB  - Vegetative storage proteins (VSPs) are thought to fulfil important nutritional
      roles during plant development and stress adaptation. Plant responses to
      mechanical wounding and herbivore damage include an activation of VSP expression.
      It was recently suggested that vsp is part of the systemic response of
      Arabidopsis to wounding. To test this proposal, we monitored the spatial
      regulation of vsp mRNAs and VSP proteins. Arabidopsis contains two vsp genes and
      real-time quantitative PCR allowed us to characterize their differential
      expression. The ratio of vsp1 to vsp2 mRNA abundance increased when plants were
      challenged with diamondback moth larvae or Egyptian cotton worms, but not when
      they were mechanically wounded. We observed a dramatic increase of vsp1 and vsp2
      mRNA as well as VSP protein levels in leaves that experienced herbivore damage.
      By contrast, there was a relatively minor increase of vsp mRNA and VSP protein
      levels in undamaged leaves of infested plants. These results clearly demonstrate
      that VSPs are part of the local plant response to herbivore attack. To obtain
      additional information on vsp regulation, we analysed a fusion of a soybean vspB
      promoter fragment to the beta-glucuronidase gene in transgenic Arabidopsis
      plants. The vspB promoter responded to both jasmonate and herbivore treatments,
      suggesting that similar signals regulate its expression in both plant species.

PMID- 11982939
TI  - Characterization of Chloroplast Clp proteins in Arabidopsis: Localization, tissue
      specificity and stress responses.
AB  - The ATP-dependent Clp protease is one of the newly identified proteolytic systems
      in plant organelles that incorporate the activity of molecular chaperones to
      target specific polypeptide substrates and avoid inadvertent degradation of
      others. We describe new nuclear-encoded ClpC (ClpC1) and ClpP (ClpP3-5) isomers
      in Arabidopsis thaliana that raise the total number of identified Clp proteins to
      19. The extra Clp proteins are localized within the stroma of chloroplasts along
      with the ClpD, -P1 and -P6 proteins. Potential differential regulation among
      these Clp proteins was analysed at both the mRNA and protein level. A comparison
      between different tissues showed increasing amounts of all plastid Clp proteins
      from roots to stems to leaves suggested the greatest abundance of proteins was in
      chloroplasts. The increases in protein were mirrored at the mRNA level for most
      ClpP isomers (ClpP1, -3, -4 and -6) but not for the three Hsp100 proteins (ClpC1,
      -C2 and -D) and ClpP5, which exhibited little change in transcript levels,
      suggesting post-transcriptional/translational regulation. Potential stress
      induction was also tested for all chloroplast Clp proteins by a series of brief
      and prolonged stress conditions. Short-term moderate and severe stresses
      (desiccation, high salt, cold, heat, oxidation, wounding and high light) all
      failed to elicit significant or rapid increases in any chloroplast Clp protein.
      However, increases in mRNA and protein content for ClpD and several ClpP isomers
      did occur during long-term high light and cold acclimation of Arabidopsis plants.
      These results reveal the great complexity of Clp proteins within the stroma of
      plant chloroplasts, and that these proteins, rather than being rapidly induced
      stress proteins, are primarily constitutive proteins that may also be involved in
      plant acclimation to different physiological conditions.

PMID- 11982940
TI  - Differences in the activity and distribution of peroxidases from three different
      portions of germinating Brassica oleracea seeds.
AB  - Peroxidase (POD, EC 1.11.1.7) activity, cellular localization and isozyme
      patterns were investigated in the seed integument, cotyledon and embryo axis of
      Brassica oleracea cv. Cappuccio during pregermination and seedling growth. Seeds
      started to germinate after 24 h of imbibition. POD activity was localized in the
      pigmented layer of the integument and in procambial strands of the cotyledon and
      embryo axis in the first 24 h of imbibition. It was localized in the integumental
      cells of palisade, pigmented and aleurone layers and in epidermal, meristematic,
      procambial cells and xylem elements of the root and hypocotyl after 48 h of
      imbibition. POD activity increased during germination and early seedling growth:
      in the integument, it reached a maximum value after 72 h of imbibition, in the
      embryo axis and cotyledons, it increased up to 144 h of imbibition. The increase
      in peroxidase activity was accompanied by the appearance of new isozymes
      correlated with the development of seedling tissues. The isozyme profile was
      characterized by nine peroxidases: isoperoxidase of 50 kDa peculiar to
      integuments, that of 150 kDa to cotyledons and that of 82 kDa to the embryo axis.
      During pregerminative phase isozymes of 84 kDa were detected in the integument
      and cotyledons, of 48.5 kDa in the embryo axis. After germination, peroxidase
      activity and the complexity of the isozyme pattern increased, suggesting that
      they play a relevant role after rupture of the integument.

PMID- 11982941
TI  - Accumulation of a 31-kDa glycoprotein in association with the expression of
      embryogenic potential by spinach callus in culture.
AB  - Calli grown from segments of spinach (Spinacia oleracea L.) root in the presence
      of gibberellic acid (GA3) plus auxin, differentiated to yield somatic embryos
      after transfer to a medium without growth regulators, while calli formed in the
      absence of GA3 failed to generate any embryos. We extracted proteins from the two
      types of callus and analysed them by polyacrylamide gel electrophoresis. Compared
      with the proteins from calli formed on medium that contained only
      naphthaleneacetic acid (NAA) as a growth regulator, the proteins from calli grown
      in the presence of GA3 included appreciably higher levels of a 31-kDa basic
      protein (pI = 8.8). The protein resembled type I ribosome-inactivating proteins
      (EC 3.2.2.22) in terms of molecular mass, isoelectric point, sequence of amino
      terminal amino acids and extent of glycosylation. The 31-kDa protein was barely
      detectable in extracts of various tissues from seedlings. Thus, it is possible
      that an increase in the relative level of this protein might be associated with
      the expression of embryogenic potential expressed by spinach callus.

PMID- 11982942
TI  - Novel jasmonate amino acid conjugates in Asparagus officinalis during harvest
      induced and natural foliar senescence.
AB  - Five jasmonates, including novel tryptophan conjugates of jasmonic acid and
      dihydrojasmonic acid, were identified in extracts from spears of Asparagus
      officinalis L. by electrospray tandem mass spectrometry. Spears were harvested
      and were held dry or with bases immersed in water. The concentrations of jasmonic
      acid, dihydrojasmonic acid, their tryptophan conjugates, cucurbic acid and methyl
      jasmonate, were measured by ELISA in spears in the 10 d following harvest. A
      transient increase that occurred in all spear tips immediately following harvest
      in the concentration of jasmonates can be attributed to a wounding response. A
      second increase in the concentration of jasmonates occurred from 7 d after
      harvest but only in dry-treated spear tips indicating that jasmonates may have
      accumulated in response to water stress. Jasmonate levels were also monitored
      during natural foliar senescence. Increased levels of jasmonates occurred after
      the onset of senescence, implicating them as a consequence rather than a cause of
      senescence.

PMID- 11982943
TI  - Cold signalling associated with vernalization in Arabidopsis thaliana does not
      involve CBF1 or abscisic acid.
AB  - In genotypes of Arabidopsis that exhibit a winter-annual flowering habit, floral
      induction in response to extended cold exposure (vernalization) is mediated by
      repression of the flowering-inhibitor gene FLC. We are interested in identifying
      components of the cold signal transduction pathway leading to FLC repression. We
      examined the potential involvement of two factors that are known to play roles in
      plant cold responses: (1) CBF1, a cold-responsive transcription factor that is
      involved in activating the cold acclimation response, and (2) the phytohormone
      abscisic acid (ABA), which has traditionally been associated with plant cold
      responses. We introduced a transgene driving constitutive expression of CBF1 into
      a winter-annual genotype of Arabidopsis. In transgenic lines expressing CBF1 mRNA
      to high levels, FLC mRNA expression was not repressed, and flowering was not
      accelerated relative to control plants. We also introduced mutations that
      compromise ABA biosynthesis or sensitivity into a winter-annual genotype and
      found that the vernalization response was not affected. Finally, we found that
      presumed increases in ABA levels, as a result of direct application of the
      hormone or severe water stress, were insufficient to substitute for cold to
      induce flowering. Taken together, these findings indicate that vernalization
      involves a pathway that is distinct from cold-response mechanisms involving CBF1,
      cold-regulated genes under CBF1 control, and ABA.

PMID- 11982944
TI  - Effect of end-of-day irradiations on polyamine accumulation in petal cultures of
      Araujia sericifera.
AB  - We have studied photoperiodic control and the effect of phytochrome
      photoconversion at the end-of-day (EOD) on polyamine (PA) accumulation in petal
      explants of Araujia sericifera. Petals from immature flowers were cultured under
      long (LD) and short (SD) days. Light was provided by Gro-lux fluorescent lamps
      (90-100 &mgr;mol m-2 s-1). Red (R), far red (FR), red followed by far-red (R-FR)
      and far-red followed by red (FR-R) light treatments were applied daily at the end
      of the photoperiod. The free and bound putrescine (Put), spermidine (Spd) and
      spermine (Spm) fractions in petal explants were determined 40 days after the
      beginning of the culture. We also aimed to clarify the involvement of PA changes
      by using two inhibitors of PA biosynthesis: D-l-alpha-difluoromethylarginine
      (DFMA) and methylglyoxal bis(guanylhydrazone) (MGBG). We found PA accumulation to
      be under photoperiodic control, and the inhibitory effect of DFMA on this
      accumulation suggests that arginine decarboxylase (ADC) is the major pathway for
      Put biosynthesis. Polyamine levels were higher under LD, mainly as a result of
      the accumulation of free and bound Put. FR-EOD treatment, which dramatically
      reduced the R : FR ratio after LD, increased the accumulation of PA, mainly as
      free Put and free and bound Spd. Sequential R-FR and FR-R-EOD treatments strongly
      increased bound Spd. The concentration of MGBG used increased total PA
      accumulation, mainly as Put. However, all EOD light treatments dramatically
      reduced Put accumulation in the presence of MGBG. This may be due to a dual role
      of FR light in PA accumulation: (1) FR per se stimulates PA production, probably
      via ADC, and (2) in the presence of MGBG, FR inhibits Put accumulation, probably
      via ethylene production.

PMID- 11982945
TI  - Detection and characterization of GTP-binding proteins in the chloroplast
      envelope of spinach (Spinacia oleracea).
AB  - Proteins binding guanosine triphosphate (GTP) have emerged as important
      regulators in several cellular processes in plants. To investigate any role of
      such proteins in chloroplast functions, we subjected envelope, stroma and
      thylakoid fractions isolated from spinach chloroplasts to two different GTP
      binding assays. With both methods, we detected GTP-specific binding only in the
      envelope fraction. Two chloroplast envelope proteins with the apparent molecular
      weights of 30.5 and 33.5 kDa, respectively, bound [alpha-32P]GTP after SDS-PAGE
      followed by electroblotting onto a PVDF-membrane and renaturation. Both proteins
      were intrinsic proteins located in the outer chloroplast envelope. Also, when the
      fractions were incubated with [alpha-32P]GTP, followed by periodate oxidation and
      borohydride reduction to cross-link GTP to proteins, two proteins in the envelope
      fraction, of apparent molecular weights of 28 and 39 kDa, appeared to
      specifically bind GTP. When agents that stimulate heterotrimeric G-proteins,
      cholera toxin or the mastoparan analogue mas7, were added to isolated chloroplast
      envelope, the binding of radiolabelled GTP to the 39 kDa protein, a protein of
      the inner chloroplast envelope, was stimulated, whereas GTP-binding of the 28 kDa
      protein, a protein of the outer envelope, was unchanged. Mas7 also stimulated
      synthesis of monogalactosyl diacylglycerol in isolated chloroplast envelope. The
      occurrence and regulation of GTP-binding proteins in the chloroplast envelope
      suggests that GTP-binding proteins could be involved in communication with the
      extraplastidic compartment during chloroplast biogenesis and development.

PMID- 11982947
TI  - Erratum.

PMID- 11982946
TI  - Abnormal etioplast development in barley seedlings infected with BSMV by seed
      transmission.
AB  - The effect of barley stripe mosaic hordeivirus (BSMV) was studied on the
      ultrastructure of etioplasts, protochlorophyllide forms and the greening process
      of barley (Hordeum vulgare cv. Pannonia) plants infected by seed transmission.
      The leaves of 7- to 11-day-old etiolated seedlings were examined by transmission
      electron microscopy, fluorescence and absorption spectroscopy. The etioplasts of
      infected seedlings contained smaller prolamellar bodies with less regular
      membrane structure, while prothylakoid content was higher than in the control.
      The protochlorophyllide content of virus-infected seedlings was reduced to 74% of
      the control. In the 77 K fluorescence spectra the relative amount of 655 nm
      emitting photoactive protochlorophyllide form decreased, and the amount of the
      645 and 633 nm emitting forms increased in the infected leaves. A characteristic
      effect was observed in the process of the Shibata-shift: 40 min delay was
      observed in the infected leaves. The results of this work proved that BSMV
      infection delays or inhibits plastid development and the formation of
      photosynthetic apparatus.

PMID- 11982948
TI  - Prions and blood: the impact on apheresis technology development.

PMID- 11982949
TI  - Removal of endotoxin in blood by polymyxin B immobilized polystyrene-derivative
      fiber.
AB  - Polymyxin B, a cationic cyclic decapeptide antibiotic, is well known to bind
      endotoxin and to neutralize its toxicity. Based on this principle, polymyxin B
      was immobilized on the chloroacetamidomethylated polystyrene fiber that is
      reinforced by polypropylene. The adsorbing capacity of the obtained fibers
      (polymyxin B immobilized fiber [PMX-F]) was evaluated on endotoxin and other
      serum components in serum and on heparin in phosphate-buffered saline.
      Fluorescein isothiocyanate-labeled or tetramethylrhodamine isothiocyanate-labeled
      lipopolysaccharide (LPS) was used as endotoxin. The measurement of the
      fluorescence intensity showed that PMX-F adsorbed these LPSs depending on their
      concentration and on amount. The adsorption of endotoxin was confirmed by
      desorption of LPS from PMX-F as well. PMX-F adsorbed serum amyloid protein A
      besides LPS, but neither C-reactive protein nor low-density lipoprotein. The
      adsorbing property of heparin was low.

PMID- 11982950
TI  - Endotoxin and cytokine removal in sepsis.
AB  - Sepsis, the leading cause of mortality in intensive care units, is a complex
      series of interrelated effects caused by the overproduction of multiple mediators
      and their unrestrained biological activity. Both proinflammatory and
      antiinflammatory mediators participate in the high complexity of sepsis and
      explain the failure of specific therapies to improve survival. Continuous
      extracorporeal therapies have been proposed as therapeutic options and as tools
      for blood purification in sepsis. Along these lines and in order to achieve
      higher clearances and mass removal rates, we studied the effects of
      plasmafiltration coupled with adsorption and provided in vitro and in vivo
      evidence that adsoprtion of multiple cytokines, activated complement components,
      and lipid mediators such as the platelet-activating factor occurs. We also showed
      that such treatment may lead to improved survival in a rabbit model of sepsis and
      to improved hemodynamics, reduced norepinephrine dose, and restoration of near-to
      normal responsiveness of blood leukocytes to endotoxin in humans. It is
      anticipated that treatment of plasma, as a modular device to conventional
      hemofiltration, may pave the way to innovative approaches in the extracorporeal
      treatment of septic patients.

PMID- 11982951
TI  - Adsorption of endotoxin by beta2-microglobulin adsorbent column (Lixelle): the
      new approach for endotoxinemia.
AB  - We previously reported that Lixelle, which was used for beta2-microglobulin (BMG)
      adsorption columns, could adsorb not only BMG but also inflammatory cytokines. We
      became interested in the application of Lixelle for patients with endotoxinemia
      and researched its ability to adsorb microorganism components in vitro using
      lipopolysaccharide (LPS) (Escherichia coli B8), endotoxin (ET) contaminated
      water. The initial concentrations of each water solution were LPS (ET 29,135
      EU/L) and contaminated water (ET 3,523 EU/L) whole blood solution was LPS (ET
      1,197.6 EU/L). Each 2.5 ml of the stock solution and adjusted diluted solutions
      contained 0.5 ml of Lixelle beads. After shaking at 37 degrees C for 2 h, ET in
      the solutions was determined using the endotoxin specific-limulus amebocyte
      lysate method. The results revealed that even though ET concentrations in LPS and
      contaminated water incubated in water solution and in whole blood were high, the
      samples containing Lixelle beads showed significant decreases. Thus, Lixelle
      beads can adsorb not only BMG but also microorganism components such as LPS and
      ET. These findings together with the ability of Lixelle to adsorb ET show the
      possibility of the application for treatment of endotoxinemia.

PMID- 11982952
TI  - A review of leukofiltration therapy for decreasing the morbidity associated with
      cardiopulmonary bypass and acute inflammatory bowel disease.
AB  - Complications of cardiopulmonary bypass (CPB) and acute inflammatory bowel
      disease (IBD) are associated with increased morbidity and cost. During
      reperfusion post-CPB, activated neutrophils adhere to microvascular endothelial
      cells mediated by cell adhesion molecules (CAMs) and cytokines/chemokines with
      subsequent myocardial damage caused by activated neutrophil-derived oxidants and
      enzymes. Leukofiltration was shown to reduce myocardial reperfusion injury and
      improve gas exchange as suggested by improvements in surrogate markers of
      inflammation and clinical end points. In acute IBD, characterized by rectal
      bleeding and protracted hospital stays, circulating neutrophils emigrate to the
      inflamed colon and adhere to microvascular endothelial cells by CAMs. Multiple
      treatments with leukofiltration in IBD were shown to induce long-term remission
      of acute IBD. Hence, leukofiltration may reduce reperfusion injury and rectal
      bleeding in CPB and IBD, respectively, and therefore decrease the morbidity and
      cost associated with these diseases.

PMID- 11982953
TI  - Effects of direct adsorption of lipoproteins apheresis on lipoproteins, low
      density lipoprotein subtypes, and hemorheology in hypercholesterolemic patients
      with coronary artery disease.
AB  - Direct adsorption of lipoproteins (DALI) apheresis has been shown to reduce
      effectively low-density lipoprotein (LDL) cholesterol and lipoprotein (a)
      concentrations. However, the effects on nontraditional risk indicators such as
      hemorheology and LDL subtypes have not been investigated so far. Five patients (2
      women, 3 men, age 53 +/- 8 years) with coronary artery disease and severe LDL
      hypercholesterolemia regularly treated with other LDL apheresis devices entered
      the study and were then treated with DALI for the first time. Hemorheological and
      lipoprotein parameters were measured before and immediately after the initial
      DALI apheresis as well as before the fourth DALI apheresis. Compared to baseline
      (before the first DALI apheresis), the following parameters were significantly
      improved (p < 0.05) after the first DALI apheresis: LDL cholesterol (69 +/- 28
      versus 208 +/- 82 mg/dl) and cholesterol in each LDL subfraction as well as
      plasma viscosity (1.23 +/- 0.04 versus 1.37 +/- 0.06 mPa), C-reactive protein,
      native blood viscosity, red cell aggregation, and red cell deformability. When
      parameters before the fourth DALI apheresis were compared to baseline, LDL
      cholesterol was still lower, and red cell deformability was still improved while
      cholesterol in each subfraction showed a statistical trend to lower
      concentrations (0.08 < p < 0.14). In conclusion, DALI apheresis not only reduces
      LDL cholesterol but also induced a significant reduction of cholesterol in all
      LDL subfractions and improved various hemorheological parameters.

PMID- 11982954
TI  - Comparison of different treatment regimens in a case of homozygous familial
      hypercholesterolemia.
AB  - The laboratory results of five periods of different treatment regimens were
      compared in a 19-year-old girl with homozygous familial hypercholesterolemia
      (FH): weekly low-density lipoprotein (LDL) apheresis sessions with dextran
      sulfate columns (LA 15, Kaneka Corporation, Osaka, Japan) without statin
      administration; weekly LDL apheresis with polyacrylate columns (DALI, Fresenius
      Adsorber Technology, Bad Homburg, Germany) without statin; LDL apheresis as in
      Period 2 with 40 mg atorvastatin daily; LDL apheresis as in Period 2 with 80 mg
      atorvastatin daily; and fortnightly LDL apheresis sessions with polyacrilate and
      administration of 80 mg atorvastatin daily. The five treatments were given in the
      above order, and each lasted at least 2 months. To compare the effectiveness of
      the different methods, the blood levels of total cholesterol, LDL-cholesterol and
      high-density lipoprotein (HDL)-cholesterol were measured before each session, and
      the percentage decreases in the blood levels of total cholesterol and LDL
      cholesterol were recorded during sessions in Periods 1 and 2. In Periods 1 and 2,
      the biological effectiveness of LDL apheresis was comparable. Atorvastatin (40 mg
      daily) improved the blood levels of total cholesterol and LDL-cholesterol, but
      lowered HDL-cholesterol values. Increasing the daily dose of atorvastatin from 40
      mg to 80 mg did not significantly improve LDL-cholesterol levels. When the time
      between two sessions was longer (Period 5), the total cholesterol and LDL
      cholesterol values worsened and were comparable to those of Period 2 during which
      there was no atorvastatin treatment. In this case of homozygous FH, weekly
      sessions of LDL apheresis in association with atorvastatin at dose of 40 mg per
      day gave the best results.

PMID- 11982955
TI  - The erythrocyte adhesiveness/aggregation test to reveal real-time information of
      rheological relevance in patients with familial and primary hypercholesterolemia
      before and following plasma exchange.
AB  - We applied an erythrocyte adhesiveness/aggregation test (EAAT) to a model of
      plasma exchange in individuals with familial and primary hypercholesterolemia.
      The significant (p < 0.0001) reduction in the concentration of fibrinogen by 56%,
      globulins by 48%, and cholesterol by 53% corresponded to the expected significant
      (p < 0.0001) reduction in the degree of erythrocyte adhesiveness/aggregation in
      the peripheral venous blood. By virtue of its being a real-time, simple, very-low
      cost, and essentially bedside technique, the EAAT might have the potential of
      disclosing information of rheological relevance immediately before, during, as
      well as following apheretical procedures administered to patients with an
      impaired rheological profile.

PMID- 11982956
TI  - Antibody reactivity of a standardized human serum protein solution against a
      spectrum of microbial pathogens and toxins: comparison with fresh frozen plasma.
AB  - In this study, we compared a standardized solution of human serum protein (HSP)
      and fresh frozen plasma (FFP) with regard to the antibody specificity against a
      number of microbial pathogens and some important pathogenicity factors of
      bacterial pathogens. Due to the clinical use of HSP and FFP for therapeutical
      plasma exchange, we have chosen a spectrum of microbial pathogens for serological
      analysis that is critical in clinical settings. With the enzyme-linked
      immunosorbent assay technique, we could show that HSP contains marked IgG
      antibody reactivity against antigens of Escherichia coli, Campylobacter jejuni,
      Enterobacter sakazakii, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae,
      Enterococcus faecalis, Chlamydia pneumoniae, and Candida albicans. Although no
      IgM antibodies against the pathogens tested could be detected in HSP, moderate
      IgA reactivity was found against 4 of 12 microbial antigens. Immunoblot analysis
      demonstrated specific IgA and IgG responses against the endoproteinase Glu-C and
      the superantigens enterotoxin A and B of S. aureus, the IgA-protease of Neisseria
      gonorrhoeae, and Shiga toxin 2 of enterohemorrhagic E. coli. By using 3 different
      HSP batches in parallel, we could demonstrate antibody reactivity against
      important microbial pathogens and toxins. This antibody profile is essentially
      more homogeneous than that of 3 batches of FFP.

PMID- 11982957
TI  - The effectiveness of intravenous human immunoglobulin treatment after
      plasmapheresis in restoring serum immunoglobulin levels: a preliminary study.
AB  - This study was performed to examine the effects of intravenous human
      immunoglobulin (IVIG) on the level of serum immunoglobulin G (IgG) and its
      subclasses after plasmapheresis in patients with autoimmune disorders. Twenty
      nine patients with predominantly rheumatoid arthritis were enrolled in this
      study. The plasmapheresis was performed by the use of double-filtration
      plasmapheresis (DFPP). Immediately after DFPP, IVIG (2.5 g, 50 ml) was
      intravenously administered. The treatment with IVIG had almost no effect on
      subjective and objective symptoms. Immediately after DFPP, the total of serum IgG
      was decreased by approximately 40%. After 24 h, the total of serum IgG recovered
      to 16% reduction in IVIG-treated patients whereas it remained at 32% reduction in
      nontreated patients. The beneficial effect of IVIG was significantly observed in
      patients who had shown 1,000-1,800 mg/dl IgG in their sera. After DFPP, IgG
      subclasses were decreased without change in the ratio of subclasses. Twenty
      percent to 30% of IgG subclasses were supplemented by the treatment with IVIG
      without change in the ratio of subclasses. These results suggested that the
      treatment with IVIG at minimal amount was safe and effective to supplement IgG
      for hypogammaglobulinemia after DFPP.

PMID- 11982958
TI  - Reactive hemophagocytic syndrome associated with thrombotic thrombocytopenic
      purpura during therapeutic plasma exchange.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, cytopenia,
      splenomegaly, and lymphohistiocytic proliferation with hemophagocytosis.
      Sporadic, familial, and reactive HLH varieties exist. The latter, also termed the
      reactive hemophagocytic syndrome (RHS), has been associated with a variety of
      infectious and noninfectious etiologies. Activation of monocytes in RHS is due to
      stimulation by high levels of activating cytokines. RHS has not been associated
      previously with thrombotic thrombocytopenic purpura (TTP). TTP is a multisystem
      disorder characterized by consumptive thrombocytopenia, microangiopathic
      hemolytic anemia, neurologic symptoms, renal impairment, and fever. We report on
      a 33 year old male patient with a classic picture of TTP who initially responded
      to therapeutic plasma exchange but then became refractory to treatment and
      developed RHS. It is likely that a specific pathophysiology involving the
      activation of neutrophils during TPE is present for the development of cytokine
      induced hemophagocytosis during TTP treatment. The consequent development of RHS
      possibly caused early TTP relapse.

PMID- 11982959
TI  - Plasma exchange versus double filtration plasmapheresis in the treatment of
      Guillain-Barre syndrome.
AB  - Previous studies have shown that both plasma exchange (PE) and double filtration
      plasmapheresis (DFPP) are effective treatments in Guillain-Barre syndrome (GBS).
      Whether PE and DFPP have similar effects in GBS is not clear. This report
      compares the therapeutic effectiveness of PE and DFPP in GBS patients treated in
      3 major hospitals in northern Taiwan. A total of 102 patients were included in
      this survey, including 39 with PE (hereafter PE group) and 63 with DFPP
      (hereafter DFPP group). Both groups showed significant improvement of disability
      scores after treatment. However, time to onset of effect was shorter (5.6 +/- 3.5
      versus 7 +/- 3.4 days, p < 0.05), and changes of disability scores were more
      prominent (1.3 +/- 0.8 versus 0.8 +/- 0.8, p < 0.05) in the PE group than the
      DFPP group. Mortality and outcome after 6 months were not different between the 2
      groups. In conclusion, both PE and DFPP are effective treatments in GBS. PE was
      superior to DFPP in short-term effectiveness. The long-term effectiveness was not
      different.

PMID- 11982960
TI  - The beneficial effects of lymphocytapheresis for treatment of nephrotic syndrome.
AB  - A considerable permeability factor (or factors) derived from circulating T cells
      has a crucial role in proteinuria of nephrotic syndrome (NS). We attempted to
      remove pathogenic T cells through lymphocytapheresis (LCAP) in 6 patients with
      primary NS, 2 patients with minimal change nephrotic syndrome (MCNS), 2 patients
      with focal segmental glomerulosclerosis (FSGS), 1 patient with membranous
      nephropathy (MN), and 1 patient with MN and FSGS using Cellsorba (Asahi Medical
      Co., Osaka, Japan). LCAP was performed 2 times in 2 consecutive weeks and was
      followed with corticosteroid therapy with or without cyclosporine A in 5
      patients. Two patients with MCNS, 1 with FSGS, and 1 with MN and FSGS showed a
      dramatic decrease of proteinuria (-30% and -94%) in their urine
      protein/creatinine ratio. Three out of 4 patients had a complete or partial
      remission (proteinuria <1g/day) within 8 weeks following immunosuppressive
      therapy. During the LCAP, T cells, especially activated T cells, decreased
      significantly in the response group. The other 2 patients, 1 with FSGS and 1 with
      MN, however, had no response to LCAP and following immunosuppressive therapy or
      low-density lipoprotein apheresis and suffered from end-stage renal failure or
      death by pneumonia. These results suggested that LCAP might have a beneficial
      effect on the treatment of NS, especially MCNS and in some patients with FSGS,
      despite varying responses to LCAP and concomitant immunosuppressive therapy.

PMID- 11982961
TI  - Rapid and persistent reduction of proteinuria following plasma exchange in a case
      of steroid-resistant focal segmental glomerulosclerosis.
AB  - We report on the case of a 45 year old male with focal segmental
      glomerulosclerosis (FSGS) in whom steroid-resistant proteinuria was reduced
      rapidly by plasma exchange. In 1994, he was admitted to our hospital because of
      massive proteinuria of several years' duration. Renal biopsy confirmed the
      diagnosis of FSGS. Proteinuria was suppressed partially with the use of
      dipyridamole. Though oral prednisolone (PSL, 30 mg/day) was effective initially,
      relapse occurred during PSL tapering. Doses of PSL up to 30 mg/day or additional
      mizoribine were ineffective. The patient was readmitted for a trial of plasma
      exchange in April 2000. Four sessions of plasma exchange with albumin replacement
      over 2 weeks immediately reduced the proteinuria from 3.2 g/day to 0.6 g/day
      without any change in medication. After discharge, proteinuria remained
      suppressed for more than 6 months despite a reduction of PSL dose to 15 mg. The
      rapid and long lasting effect of plasma exchange in the present case argues for
      the role of a putative circulatory factor in the pathogenesis of proteinuria in
      FSGS.

PMID- 11982962
TI  - Tick-borne diseases in transfusion medicine.
AB  - Ticks are effective vectors of viral, bacterial, rickettsial and parasitic
      diseases. Many of the tick-borne diseases (TBDs) are of significance to
      transfusion medicine, either because of the risks they pose to the blood supply
      or the necessity for blood products required in their treatment. The transmission
      of tick-borne pathogens via blood transfusion is of global concern. However,
      among transfusion medicine practitioners, experience with most of these
      microorganisms is limited. Transfusion transmission of TBDs has been documented
      largely by means of single case reports. A better understanding of the
      epidemiology, biology and management of this group of diseases is necessary in
      order to assess the risks they pose to the blood supply and to help guide
      effective prevention strategies to reduce this risk. Unique methods are required
      to focus on donor selection, predonation questioning, mass screening and
      inactivation or eradication procedures. The role of the transfusion medicine
      service in their treatment also needs to be better defined. This article reviews
      the growing body of literature pertaining to this emerging field of transfusion
      medicine and offers some recommendations for transfusionists in dealing with
      TBDs.

PMID- 11982963
TI  - Detection of hepatitis C core antigen in serum or plasma as a marker of hepatitis
      C viraemia in the serological window-phase.
AB  - A new immunoassay for the detection of hepatitis C core antigen (HCVcoreAg) in
      peripheral blood during serological window-phase was evaluated among healthy
      blood donors, commercially available hepatitis C virus (HCV) seroconversion
      panels and in-house specimens from individuals undergoing seroconversion. Among
      1964 low-risk blood donor samples, seven samples were initially reactive but only
      one was repeat reactive. Reactivity of this specimen was not confirmable by
      neutralization with specific anti-HCV core antibody, and the sample was negative
      for HCV RNA by polymerase chain reaction (PCR). The specificity of the HCVcoreAg
      enzyme-linked immunosorbent assay (ELISA) was 99.95%. In seven commercially
      available HCV seroconversion panels, HCVcoreAg appeared 23-46 days earlier than
      anti-HCV antibody by third generation assay. Additional testing with specimens
      from patients undergoing anti-HCV seroconversion indicated that HCVcoreAg becomes
      undetectable by the present test format soon after the onset of antibody. This
      test may be considered as an alternative to nucleic amplification techniques
      (NAT) for blood donor HCV screening. Additional development of technology for
      detecting HCVcoreAg may be useful for patient diagnosis and therapy monitoring.

PMID- 11982964
TI  - Electrochemiluminescent detection of bacteria in blood components.
AB  - Transfusion-transmitted bacterial infections cause significant patient morbidity
      and mortality. This study aimed to improve the sensitivity of a nucleic acid
      based electrochemiluminescence (ECL) assay for pretransfusion bacterial testing
      of cellular blood components. The approach is dependent on the detection of
      bacterial 16S ribosomal RNA (rRNA). The modifications studied included the use of
      a chaotrope-based lysis buffer with high-energy mechanical cell disruption by
      RiboLysis, increased ruthenium (Ru2+) labelling per 16S rRNA molecule and
      concomitant use of fluorescent nucleic acid dyes (CyQUANT, Syto 17 red and Syto
      61 red). The methodological changes made did lead to more effective bacterial
      cell disruption and enhanced ECL signal generation. Nevertheless, assay
      sensitivity was only slightly improved at approximately 10(4)-10(5) colony
      forming units per mL (CFU mL(-1)) and the results were highly inconsistent. The
      method is still not sensitive to the required 10(2) CFU mL(-1) and remains
      impractical for routine use in blood centres.

PMID- 11982965
TI  - A pilot study to assess physician knowledge in transfusion medicine.
AB  - INTRODUCTION: An assessment of transfusion medicine knowledge and practice in
      Canada was carried out over a 3-week period. METHODS: Fifty-five questions were
      posed to evaluate both basic information on blood and blood products and on
      clinical use. The form was distributed through the Canadian Society for
      Transfusion Medicine with designated individuals asked to handle regional
      distribution. Some used provincial mailing lists, others distributed within each
      hospital. Approximately, 2000 forms were sent, including 500 in French. RESULTS:
      A total of 294 forms were returned; answers were recorded as 'correct',
      'incorrect', 'no answer' or with 'added comments'. Overall, 52% of the questions
      were answered correctly or were answered with qualifying comments. In clinical
      practice questions, 63% were answered correctly or with qualifying comments.
      Basic knowledge questions drew correct answers in 37% of the cases. Several
      issues were answered poorly. The volume of an apheresis plasma unit was correctly
      estimated by less than 10% of respondents with many understanding the volume (500
      600 mL) by as much as 300-400 mL. Anaesthesiologists responded most often (21%);
      few haematologists participated (4%). Provincial response varied: most were
      received from Ontario (30%) and British Columbia (22%). CONCLUSIONS: The answers
      show that clinical application of transfusion is generally accompanied by a
      questioning process - it is not entirely by rote. Basic knowledge about products
      needs improvement.

PMID- 11982966
TI  - Providing feedback to users on unacceptable practice in the delivery of a
      hospital transfusion service--a pilot study.
AB  - The Serious Hazards of Transfusion Scheme's (SHOT) annual report continues to
      emphasize the importance of investigating serious transfusion errors. It is now
      recognized that lessons can also be learnt from near-miss events as these occur
      more frequently than serious errors in transfusion. One of the key features in
      developing a culture that can promote safety in relation to transfusion is
      providing feedback to staff on what is acceptable and unacceptable practice. We
      have developed a scoring system based on the number of serious errors and near
      misses that occur in the transfusion service to provide feedback to staff on
      their performance in relation to the administration of blood components and blood
      products. This was developed as part of an ongoing error logging system that we
      have previously described. The implementation of this feedback has resulted in an
      increased awareness within our organization of safety issues in relation to
      transfusion, and has highlighted the importance of the detection and correction
      of less serious errors.

PMID- 11982967
TI  - In vitro antiviral and antibacterial activity of commercial intravenous
      immunoglobulin preparations--a potential role for adjuvant intravenous
      immunoglobulin therapy in infectious diseases.
AB  - The identification of specific antimicrobial activity of intravenous
      immunoglobulin (IVIG) preparations against particular microbial pathogens can
      assist in determining their therapeutic potential for specific infectious
      diseases. We analysed five different commercial IVIG preparations for the
      presence of antibodies directed against a large panel of viral, bacterial, fungal
      and parasitic pathogens. All IVIG batches contained high activity against
      herpesviruses types 1, 2, 6 and 7, as well as against varicella zoster virus,
      Epstein-Barr virus (EBV), measles, mumps, rubella and parvovirus B19. Some IVIG
      batches also had a significant activity against adenovirus and Saint Louis
      encephalitis virus. The IVIGs held high activity against several bacterial
      pathogens, including Mycoplasma pneumonia, Chlamydia pneumonia, Helicobacter
      pylori and tetanus. No activity was found against various parasitic and fungal
      pathogens. Our findings may provide further support for the use of IVIG for the
      prevention and treatment of infections caused by specific viral and bacterial
      pathogens.

PMID- 11982968
TI  - Recombinant forms of glycophorin C as a tool for characterization of epitopes for
      new murine monoclonal antibodies with anti-glycophorin C specificity.
AB  - Glycophorin C (GPC) and glycophorin D (GPD) are minor but important components of
      human RBC membranes. They carry the high-frequency antigens Ge2, Ge3 and Ge4 of
      the Gerbich blood group system. The epitopes for five new monoclonal antibodies
      (MoAbs) with anti-GPC specificity were characterized. Two antibodies (4G11 and
      5B11) reacted with glycosylated N-terminal epitopes, and three reacted with
      internal epitopes of GPC. Pepscan analysis showed that the MoAb RB11 required for
      binding the EPDP sequence, occurring twice in GPC polypeptide chain. The MoAb
      7F11 recognized the sequence 13PLSLEPDP20, and the MoAb RB8 did not react with
      synthetic peptides. Further characterization of the internal epitopes was
      performed in fluorescence-activated cell sorter (FACS) with the use of
      recombinant GPC and its variant forms transiently expressed on COS-7 cells. The
      results indicated that the MoAb RB11 recognized distinctly its target sequence
      EPDP only in a normal GPC molecule. The reactivity of the MoAb 7F11 with the
      PLSLEPDP sequence was confirmed and found to be enhanced by the O-glycan at the
      Ser15 residue. The MoAb RB8 recognized the glycopeptidic epitope in proximity to
      the Ser15 residue, requiring the presence of O-glycan. The combination of
      immunochemical techniques with the use of the recombinant forms of GPC has made
      it possible to define the role of sugar chains in the recognition of peptidic
      epitopes in glycosylated antigen and sheds new light on the Gerbich system
      antigens.

PMID- 11982972
TI  - The prospects for multiple-marker screening for preterm delivery: does
      transvaginal ultrasound of the cervix have a central role?

PMID- 11982973
TI  - Teaching new procedures.

PMID- 11982974
TI  - Uterine artery score and perinatal outcome.
AB  - OBJECTIVE: To evaluate a modified uterine artery score based on the pulsatility
      index and presence or absence of notching in the Doppler velocity waveform
      recorded from both uterine arteries in relation to the perinatal outcome.
      METHODS: A retrospective analysis was performed in 741 third-trimester high-risk
      pregnancies. The uterine artery score was constructed assigning one point to each
      abnormal parameter-high pulsatility index and presence of notch-thus ranging from
      0 (normal findings in both uterine arteries) to 4 (notch and high pulsatility
      index in both uterine arteries). In a subgroup with lateral placenta (n = 359),
      two definitions of abnormal pulsatility index were compared. In the uniform
      uterine artery score, a pulsatility index > 1.20 in both uterine arteries was
      considered abnormal, disregarding the placental location; in the subgroup with
      lateral placenta, the high pulsatility index was defined as > 1.00 on the
      placental side and > 1.40 on the non-placental side. RESULTS: Receiver-operating
      characteristic curves did not reveal any difference in the diagnostic capacity
      between the group with a uniform uterine artery score and the subgroup with
      lateral placenta (P = 0.54). In the total material, the odds ratios and linear
      regression analysis showed an increased risk for an adverse perinatal outcome
      with increasing uterine artery score (P < 0.01). At a uterine artery score > 2,
      there was a significantly increased risk for operative delivery for fetal
      distress, neonatal intensive care unit admission, 5-min Apgar score < 7, preterm
      delivery and delivery of a small-for-gestational age fetus. CONCLUSION: In high
      risk third-trimester pregnancies, Doppler velocity waveforms of the uterine
      arteries can be evaluated using the uterine artery score disregarding the
      placental location. The uterine artery score possesses a high predictive value
      regarding adverse perinatal outcome.

PMID- 11982975
TI  - Platelet changes and subsequent development of pre-eclampsia and fetal growth
      restriction in women with abnormal uterine artery Doppler screening.
AB  - OBJECTIVES: To investigate whether, in women with abnormal uterine artery
      Doppler, platelet volume and function will identify a subgroup of women at
      increased risk of pre-eclampsia and intrauterine growth restriction and whether
      in-vitro platelet aggregation precedes the onset of clinical disease. DESIGN:
      Platelet number, volume and aggregation induced by collagen or adenosine 5'
      diphosphate were evaluated in 16 non-pregnant controls, 29 pregnant women with
      normal uterine artery Doppler and 31 pregnant women with abnormal Doppler, hence
      at risk of pre-eclampsia and intrauterine growth restriction at 23 weeks. Outcome
      of pregnancy was recorded in each case. RESULTS: Twelve women in the group with
      abnormal uterine artery Doppler subsequently developed pre-eclampsia and/or
      intrauterine growth restriction. All women with normal uterine artery Doppler had
      a normal pregnancy outcome. No differences in platelet count or in vitro platelet
      aggregation induced by collagen were observed between the groups. Mean platelet
      volume was greater in those with abnormal Doppler who had intrauterine growth
      restriction or normal pregnancy outcome compared with normal Doppler (10.3 and
      10.3 vs. 9.4 fL, P = 0.004 and P = 0.01, respectively). Aggregation induced by
      adenosine diphosphate was higher in women with abnormal Doppler who developed pre
      eclampsia or intrauterine growth restriction compared with those with normal
      outcomes (66.5 and 66.5 vs. 21%, P = 0.02, P = 0.03, respectively). CONCLUSIONS:
      Women with abnormal uterine artery Doppler at 23 weeks show alterations in mean
      platelet volume and platelet function that relate to subsequent adverse outcome.

PMID- 11982976
TI  - Transient hydropic signs in the donor fetus after fetoscopic laser coagulation in
      severe twin-twin transfusion syndrome: incidence and clinical relevance.
AB  - OBJECTIVE: To evaluate the incidence, characteristics, and impact on perinatal
      outcome of the development of hydropic signs in the donor fetus after laser
      coagulation for severe twin-twin transfusion syndrome in the second trimester.
      METHODS: Forty cases of second-trimester severe twin-twin transfusion underwent
      fetoscopic laser coagulation of placental anastomoses and were followed up with
      serial ultrasound up to 14 days after therapy. Ultrasound scans were performed
      just before, and on days 1, 3, 5 and 14 after therapy, and fetuses were monitored
      for the presence of hydropic signs (skin edema, pleural effusion, ascites and
      pericardial effusion). Response to therapy and perinatal outcome in terms of
      neonatal survival were recorded for all cases. RESULTS: Four recipients (10%) and
      three donors (7.5%) died over the first 72 h after therapy. During the study
      period, two recipients (5.5%) developed frank hydrops fetalis, and eventually
      died in utero. Ten donors (27.0%) developed one or more hydropic signs. In nine
      (90%), signs were mild or moderate and transient (mean, 3.2 days), while in one
      case hydrops worsened and the fetus eventually died. No donors with transient
      hydrops died in utero, and two died postnatally due to extreme prematurity.
      Gestational age at procedure and deepest amniotic fluid vertical pocket were
      similar between hydropic and non-hydropic donors. Discrepancy in estimated fetal
      weight at procedure was significantly lower in donors developing hydrops (9.6
      (SD, 6.4) vs. 17.8 (14.4)%,P = 0.018). In pregnancies with hydropic donors,
      gestational age at delivery (33.1 (3.4) vs. 29.7 (3.5) weeks,P = 0.015) and birth
      weight for recipient (2392 (423) vs. 1631 (576) g, P < 0.001) and donor (1908
      (774) vs. 1281 (583) g,P = 0.021) were significantly higher. The development of
      transient hydrops had no influence on neonatal survival at 28 days nor on the
      rate of clinical resolution of intertwin transfusion. CONCLUSIONS: Transient
      hydropic signs may develop in a proportion of donor fetuses after laser
      coagulation for severe twin-twin transfusion syndrome. This phenomenon is
      normally not associated with a poor prognosis, and possibly indicates an
      hemodynamic adaptation response following interruption of the transfusion
      process.

PMID- 11982977
TI  - Prenatal diagnosis and management of fetuses with liver hemangiomata.
AB  - OBJECTIVES: To study the relationship between prenatal appearance and perinatal
      outcome of fetuses with hepatic hemangiomata with special emphasis on criteria
      that may help to improve perinatal management. METHODS: In a tertiary referral
      center six fetuses with hepatic hemangiomata were evaluated by gray-scale, color,
      and pulsed wave Doppler ultrasound between 1994 and 2000. Fetal blood sampling
      was performed in four cases. All data (computerized files and video tapes) were
      analyzed retrospectively. RESULTS: Two fetuses showed very similar sonographic
      findings. They had an isolated large ('giant') round hepatic hemangioma (diameter
      43 and 68 mm, respectively) supplied by one hepatic artery and drained by one
      hepatic vein, both of them showing high velocity and low pulsatility blood flow.
      Fetal blood count and coagulation parameters were normal in one case, whereas the
      other fetus showed a Kasabach-Merritt sequence with severe thrombocytopenia (10
      platelets/nL) and mild disseminated intravascular coagulation. Intrauterine
      platelet transfusion was performed immediately prior to planned Cesarean
      delivery. Rapid platelet consumption continued postnatally, requiring several
      thrombocyte transfusions. Platelet counts stabilized only after tumor resection
      on the second day of life. One fetus with diffuse neonatal hemangiomatosis
      developed high-output cardiac failure with hydrops in addition to Kasabach
      Merritt sequence (15 platelets/nL), and died following premature delivery. Three
      fetuses, however, showing an isolated small hyperechogenic hepatic hemangioma (5,
      5, and 6 mm in diameter, respectively) did not develop any perinatal
      complications. CONCLUSION: Large fetal liver hemangiomata and diffuse
      hemangiomatosis may cause severe perinatal complications, particularly high
      output cardiac failure and/or Kasabach-Merritt sequence with severe consumption
      of platelets and clotting factors and hemolytic anemia. Fetal blood sampling
      enables the prenatal detection of these potential complications, allowing
      critical modification of perinatal management such as intrauterine platelet
      transfusion, especially directly before delivery. In contrast, isolated small
      hyperreflexic hepatic hemangiomata do not appear to be associated with any of
      these fetal and postnatal sequelae.

PMID- 11982978
TI  - Ultrasound evaluation of the fetal skull base throughout pregnancy.
AB  - OBJECTIVE: To construct nomograms for cranial base parameters of normal fetuses.
      STUDY DESIGN: A cross-sectional study of 386 normal singleton fetuses at 14-40
      weeks' gestation. Measurements of the length and width of the sphenoid bone
      anteriorly and the otic cartilage posteriorly and of the angles between the
      ridges were obtained. RESULTS: Nomograms of the length and width of sphenoid
      ridge and otic cartilage, and of the angles in the cranial fossae are presented.
      A linear growth function was observed between cranial base measurements (sphenoid
      ridge length, otic cartilage length, cranial base angles) and gestational age,
      femur length and biparietal diameter. CONCLUSION: Measurements of the length of
      cranial base ridges and the angles between them can be obtained easily in the
      second and third trimesters and might prove useful in the evaluation of
      pregnancies at high risk for associated fetal abnormalities.

PMID- 11982979
TI  - Fetal gastric size in normal and abnormal pregnancies.
AB  - OBJECTIVE: The aim of this observational study was to construct an ultrasound
      index of fetal gastric size for the prenatal detection of congenital digestive
      tract obstruction. SUBJECTS: A total of 386 fetal measurements were performed in
      routine ultrasonographic examinations of women with normal singleton pregnancies
      between 18 and 39 weeks of gestation. Gastric measurements were also performed in
      13 fetuses with digestive tract obstruction. METHODS: The ultrasound plane which
      included the pylorus and which provided the largest stomach area was used for
      definition and measurement of gastric area and maximal longitudinal dimension.
      The transverse section at the center of the gastric corpus was used for
      transverse and anteroposterior dimensions. Gastric volumes were calculated as a
      prolate ellipsoid. The gastric area ratio was defined as the gastric area divided
      by the transverse abdominal area. Biparietal diameter (BPD) and abdominal
      transverse area were also measured. RESULTS: The fetal gastric area was
      significantly correlated with fetal gastric volume (r = 0.91) and gestational age
      (r = 0.74). However, the correlation coefficient for gastric area with
      gestational age was smaller than those of the BPD (r = 0.97) with gestational age
      and abdominal transverse area with gestational age (r = 0.97). Gastric area ratio
      decreased slightly towards term. The gastric area ratio was below the 95%
      confidence intervals for the predicted values in all five fetuses with esophageal
      atresia, and exceeded the 95% confidence intervals in seven of the eight fetuses
      with duodenal atresia or intestinal tract obstruction. CONCLUSION: Fetal gastric
      area correlates with ultrasound-determined gastric volume measurements and
      appears to be useful in the assessment of digestive tract anomalies.

PMID- 11982980
TI  - Comparison of three-dimensional, two-dimensional and color Doppler ultrasound in
      predicting the presence of a nuchal cord at birth.
AB  - OBJECTIVES: To compare the use of two-dimensional, color Doppler and three
      dimensional ultrasound for predicting the presence of a nuchal cord at birth.
      METHODS: Eighty-five singleton pregnancies without nuchal cord and 35 with nuchal
      cord (30 with a single coil of cord, four with a double coil, and one in which
      the cord was coiled around the neck three times) were studied within 1 week
      before delivery using transabdominal three-dimensional sonography. Two
      dimensional and color Doppler ultrasound were also conducted for comparison.
      RESULTS: Two-dimensional, color Doppler and three-dimensional sonography
      identified in utero 24 (69%), 29 (83%) and 25 (71%), respectively, of the cases
      of nuchal cord found at birth. There were no significant differences in overall
      diagnostic indices of each diagnostic modality for detecting nuchal cord.
      However, the ability to view the nuchal cord (subjective assessment of the ease
      of visualization of nuchal cord) was better with three-dimensional sonography
      than with two-dimensional or color Doppler ultrasound. CONCLUSIONS: Three
      dimensional surface imaging does not provide more useful diagnostic information
      compared with two-dimensional and color Doppler ultrasound for detecting nuchal
      cord in utero.

PMID- 11982981
TI  - Elective cerclage vs. ultrasound-indicated cerclage in high-risk pregnancies.
AB  - OBJECTIVE: To compare pregnancy outcome after elective vs. ultrasound-indicated
      cervical cerclage in women at high risk of spontaneous mid-trimester loss or
      early preterm birth. METHODS: This was a retrospective study comparing two
      management strategies in women with singleton pregnancies who had at least one
      previous spontaneous delivery at 16-33 weeks of gestation. One group was managed
      by the placement of an elective cerclage at 12-16 weeks and the other group had
      transvaginal ultrasound examinations of the cervix at 12-15+6, 16-19+6, and 20
      23+6 weeks and cervical cerclage was carried out if the cervical length was 25 mm
      or less. RESULTS: A total of 90 patients were examined, including 47 that were
      managed expectantly and 43 treated by elective cerclage. In the expectantly
      managed group, 59.6% (28/47) required a cervical cerclage. We excluded from
      further analysis three patients who were lost to follow-up and three because of
      fetal death or iatrogenic preterm delivery. Miscarriage or spontaneous delivery
      before 34 weeks' gestation occurred in 14.6% (6/41) of the elective cerclage
      group, compared with 20.9% (9/43) in the expectantly managed group (chi2 = 0.219,
      P = 0.640). CONCLUSION: In women at increased risk of spontaneous mid-trimester
      or early preterm delivery, a policy of sonographic surveillance followed by
      cervical cerclage in those with a short cervix reduces the need for surgical
      intervention without significantly increasing adverse pregnancy outcome.

PMID- 11982982
TI  - Teaching invasive perinatal procedures: assessment of a high fidelity simulator
      based curriculum.
AB  - OBJECTIVE: Learning curves pose a difficult problem in the teaching of technical
      skills: how do you teach procedural skills without compromising patients' health?
      A simulator-based curriculum has been designed to minimize the risks to patients
      undergoing amniocentesis by shifting the learning curve away from patients and
      into the laboratory. This study evaluated the effectiveness of a high-fidelity
      simulator-based curriculum in improving the performance of amniocentesis by
      obstetric trainees. DESIGN: Thirty trainees received a course on the practice of
      amniocentesis. The curriculum consisted of a lecture, a syllabus, and a hands-on
      training session with the simulator. Pre- and post-training performance were
      evaluated with two rating scales. Training and performance evaluation were
      completed using the same simulator. The effectiveness of the simulator-based
      workshop and the effect of year of training were assessed using a two-way
      analysis of variance. RESULTS: Performance scores improved from a mean score of
      55% to 94% using checklist scoring and from 57% to 88% using global ratings. The
      two-way analysis of variance revealed a significant effect of training (F1,60 =
      43.57; P < 0.001) accounting for 45% of the variance in scores, and a significant
      effect of experience level (F2,60 = 9.16; P < 0.001) accounting for 25% of the
      variance in scores. CONCLUSIONS: A comprehensive curriculum based on a high
      fidelity simulator was effective at improving skills demonstrated on the
      simulator. The challenge remains to establish that skills acquired on a simulator
      are transferable to the clinical setting.

PMID- 11982983
TI  - Evaluation of cycle-to-cycle variation of endometrial responsiveness using
      transvaginal sonography in women undergoing assisted reproduction.
AB  - OBJECTIVES: To investigate the variation of endometrial responsiveness between
      cycles within the same women undergoing assisted reproduction. METHODS: The
      sonographic endometrial thickness in ovarian stimulation cycles was compared with
      that of subsequent natural cycles. One hundred and thirty-six ovarian stimulation
      cycles of in-vitro fertilization and embryo transfer were evaluated. Women who
      did not conceive in in-vitro fertilization cycles were subsequently seen in
      natural cycles (n = 97) or the next in-vitro fertilization cycle (n = 39). Based
      on a receiver-operating characteristics (ROC) curve using endometrial thickness
      to predict pregnancy, the first in-vitro fertilization cycles were classified
      according to the endometrial thickness as optimal (> 8 mm) in 98 cycles, or
      suboptimal (< or = 8 mm) in 29 cycles. Similarly, spontaneous cycles were
      classified as suboptimal (< or = 7 mm) in 28 cycles and optimal (> 7 mm) in 69
      cycles. RESULTS: The pregnancy rates were significantly lower (P < 0.05; Fisher's
      Exact test) in the suboptimal group in both the in-vitro fertilization and frozen
      embryo transfer cycles. There was a strong correlation (r2 = 0.745) and a
      significant difference (P < 0.001; Wilcoxon signed rank sum test) between the
      endometrial thickness of stimulation and natural cycles. CONCLUSION: It is
      possible to predict the occurrence of optimal or suboptimal endometrial response
      in natural cycles of women, after evaluation in stimulated cycles, with a high
      degree of reliability. Risk of implantation failure can be identified before
      subsequent treatment cycles and adjuvant therapeutic strategies may be planned to
      improve the endometrial response before embryo transfer.

PMID- 11982984
TI  - Detection of central pelvic recurrent disease with transvaginal color Doppler
      ultrasound in women treated for gynecological malignancy.
AB  - OBJECTIVE: To evaluate color Doppler characteristics of small recurrent tumors
      detected within the central pelvis in follow-up patients treated for
      gynecological malignancy. PATIENTS AND METHODS: A prospective study was performed
      on 340 patients who were being monitored following treatment for gynecological
      malignancies. A selected group of 27 patients, with small pelvic masses located
      in the central region of the pelvis, underwent a color Doppler examination. A
      subjective assessment of the vascularization (vascular score), the lowest
      resistance index (RI), the highest peak velocity (PSV) and the highest time
      averaged maximum velocity (TAMXV) of the vessels detected within the lesion were
      analyzed. RESULTS: In 16 patients the pelvic mass was found to be benign while in
      11 patients a malignant recurrence was diagnosed. Gray-scale examination could
      not differentiate between benign and malignant lesions. The color score of tumor
      recurrences was significantly higher in comparison to that in benign lesions
      (color score 3 in 54% vs. 0%, P < 0.005). The malignant lesions showed
      significantly lower mean values of RI and significantly higher mean values of PSV
      and TAMXV when compared with benign lesions (0.39 +/- 0.09 vs. 0.81 +/- 0.22, P <
      0.0001; 19.3 +/- 4.7 vs. 10.5 +/- 5.6 cm/s, P < 0.0001; 8.9 +/- 3.7 vs. 4.3 +/-
      2.7 cm/s, P < 0.005). CONCLUSIONS: Color Doppler analysis added to transvaginal
      gray-scale ultrasonography seems to be a helpful tool in the diagnosis of
      recurrent tumors in the central region of the pelvis.

PMID- 11982985
TI  - Ultrasound imaging of paravaginal defects in women with stress incontinence
      before and after paravaginal defect repair.
AB  - OBJECTIVE: The aim of our study was to analyze whether transabdominal and
      introital sonography can identify paravaginal defects and to determine changes
      that occur following paravaginal defect repair and Burch colposuspension.
      METHODS: Twenty women with genuine stress incontinence took part in this
      prospective study. The mobility of the bladder neck was assessed transperineally
      with a curved array probe following instillation of 300 mL saline. The same probe
      was used transabdominally to determine the presence of paravaginal defects.
      Introital examination using a transvaginal probe was then performed to determine
      the presence of paravaginal defects. The same measurements were performed
      following Burch colposuspension and paravaginal defect repair. RESULTS: There
      were significant differences in bladder neck position and mobility before and
      after surgical intervention. In 18 women before surgery, transabdominal
      ultrasound identified unilateral or bilateral paravaginal defects. Eight
      unilateral defects were found on the right side but only two were found on the
      left side. In eight women, the defect was bilateral. The introital approach
      obtained similar results apart from in two patients with a bilateral defect in
      whom it indicated a unilateral right defect. Between the first and second weeks
      following the operation transabdominal ultrasound found no paravaginal defects in
      16 women and introital ultrasound found no paravaginal defects in 18 women. We
      were unable to visualize the region of the paravaginal defect in two women using
      transabdominal ultrasound because the abdominal wall was edematous after surgery.
      Five to 6 weeks after the operation, our results were confirmed by abdominal and
      introital ultrasound in all cases. No paravaginal defects were found in any of
      the patients after paravaginal defect repair. CONCLUSION: Our clinical study
      suggests that ultrasound scanning should be performed to confirm the presence of
      paravaginal defects and that paravaginal defect repair may be added to Burch
      colposuspension for the treatment of genuine stress incontinence, as an operation
      to correct cystourethrocele and the posterior urethrovesical angle.

PMID- 11982986
TI  - Intrauterine diagnosis and management of congenital goitrous hypothyroidism.
AB  - The intrauterine recognition and treatment of congenital goitrous hypothyroidism
      may not only reduce the obstetric complications associated with large goiters,
      but possibly improve the prognosis for normal growth and mental development of
      affected fetuses. We present a case of fetal goiter diagnosed at 29 weeks of
      gestation following routine ultrasound examination. Fetal blood sampling
      performed at this time confirmed the presence of fetal hypothyroidism. Treatment
      was performed using a series of intra-amniotic injections between 31 and 36
      weeks, initially with tri-iodothyronine (T3) and subsequently with thyroxine.
      During this period, shrinkage of the fetal goiter, increasing neck flexion and
      resolution of the polyhydramnios was observed. Following birth, neonatal serum
      thyroid-stimulating hormone levels were within the normal range but thyroxine was
      reduced. The baby was started on daily oral thyroxine and, on examination 7 weeks
      following birth, he appeared clinically and chemically euthyroid. In the absence
      of maternal thyroid disease, fetal goiter is extremely rare, with only seven
      cases previously reported in the English literature to have used intra-amniotic
      thyroxine injections as a form of treatment. This report reviews the current
      literature regarding the diagnosis and intrauterine management of fetal goiter
      and considers the possibility of T3 therapy in future cases of congenital
      hypothyroidism.

PMID- 11982988
TI  - Prenatal diagnosis of 22q11 microdeletion in an early second-trimester fetus with
      conotruncal anomaly presenting with increased nuchal translucency and bilateral
      intracardiac echogenic foci.
AB  - We report on a 16-week fetus, in which detection of increased nuchal translucency
      thickness and bilateral intracardiac echogenic foci led to the prenatal diagnosis
      of truncus arteriosus communis, interruption of the aortic arch and aplastic
      thymus. Cytogenetic examination confirmed a 22q11.2 microdeletion consistent with
      the suspected CATCH 22 syndrome. Subsequently hydrops fetalis developed and the
      fetus died in utero at 18 weeks. This case report supports the hypothesis that
      both cardiac failure and left ventricular outflow tract obstruction may cause
      increased nuchal translucency thickness. The association between increased nuchal
      translucency thickness and CATCH 22 syndrome should be considered in diagnostic
      procedures. The sonographic diagnosis of both increased nuchal translucency
      thickness and intracardiac echogenic foci requires specialist ultrasonography and
      echocardiography. In particular, identification of right-sided or bilateral
      echogenic foci should prompt further detailed examination.

PMID- 11982987
TI  - Antenatal diagnosis and treatment of a case of fetal goitrous hypothyroidism
      associated with high-output cardiac failure.
AB  - A case of fetal goitrous hypothyroidism associated with high-output cardiac
      failure is presented. At 32 weeks of gestation, the antenatal diagnosis of goiter
      was made based on ultrasound examination, and the fetal thyroid function was
      examined by amniocentesis and cordocentesis. Color and pulsed Doppler
      examinations demonstrated a high vascular flow pattern in the goiter and marked
      elevation of the maximum velocity in the common carotid artery at the level of
      the neck. It was suspected that arteriovenous shunting through the large goiter
      resulted in high-output cardiac failure with cardiomegaly and pleural effusion.
      The fetus was treated by injection of levothyroxine sodium into the amniotic
      fluid at 33 weeks of gestation and the goiter thereafter decreased in size, with
      subsequent improvement of the high-output cardiac failure. The maximum velocity
      in the common carotid artery fell rapidly before the shrinkage of the fetal
      goiter and in parallel with the fetal level of thyroid stimulating hormone.

PMID- 11982989
TI  - Prenatal diagnosis of intrapulmonary arteriovenous malformation: sonographic and
      pathomorphological findings.
AB  - Vessel malformations, which are very rare, can be diagnosed prenatally using
      color Doppler sonography. We present a case of a fetus which, at first prenatal
      presentation at 27 weeks, was diagnosed as having an intrapulmonary arteriovenous
      malformation. On the basis of the gray-scale sonographic findings of cardiomegaly
      and dilatation of the right pulmonary vein and right pulmonary artery, color
      Doppler sonography was performed which identified an arteriovenous malformation
      of the right lung. By means of pulsed Doppler sonography it was possible to
      determine the hyperdynamic blood circulation in the incoming and outgoing vessels
      of the vascular malformation: right pulmonary artery peak systolic velocity = 90
      cm/s and end-diastolic velocity = 30 cm/s; right pulmonary vein peak systolic
      velocity = 60 cm/s and end-diastolic velocity = 30 cm/s. The fetus went on to
      develop hydrops as the result of an arteriovenous valve insufficiency. At 30
      weeks' gestation a Cesarean section was performed and the neonate died due to
      respiratory and hemodynamic problems during catheter insertion. The autopsy
      provided pathoanatomical confirmation of the prenatal diagnosis of an
      arteriovenous malformation of the right lung. There was no evidence of hereditary
      hemorrhagic telangiectasia.

PMID- 11982990
TI  - Prenatal sonographic findings of thalamic cavernous angioma.
AB  - A cavernous angioma of the thalamus is a rare congenital brain tumor. We report
      the perinatal management and follow-up to 2 years in a case diagnosed in utero at
      37 weeks of gestation, and review the literature.

PMID- 11982991
TI  - Sonographic features of anal atresia at 12 weeks.
AB  - Anorectal atresia results from abnormal development of the anorectal septum.
      Prenatal diagnosis is difficult but the condition may be suspected by the
      sonographic demonstration of a dilated colon. We present the sonographic features
      of a fetus with anal atresia and a ventricular septal defect at 12 weeks of
      gestation. This case illustrates that a dilated colon may be present in
      association with fetal anal atresia as early as 12 weeks.

PMID- 11982992
TI  - Prenatal diagnosis of Caroli's disease.

PMID- 11982993
TI  - Contribution of volumetric three-dimensional ultrasound to the prenatal diagnosis
      of a soft anal tumor.

PMID- 11982995
TI  - Early trophoblast invasion and fetal loss in chromosomally abnormal conceptions.

PMID- 11982994
TI  - Sonographic findings in a case of congenital pyloric diaphragm.

PMID- 11982996
TI  - In-utero defecation.

PMID- 11983000
TI  - The 2000 lifetime achievement award.

PMID- 11983001
TI  - Lifetime achievement award lecture, Toronto 2000.

PMID- 11983002
TI  - Transcription factor activation in response to cutaneous injury: role of AP-1 in
      reepithelialization.
AB  - Reepithelialization is the process responsible for restoring an intact epidermis
      following cutaneous injury. A change in the activity of keratinocytes is required
      for reepithelialization to occur, and this is likely to be regulated by the
      altered expression of effector genes, mediated by transcription factors. The
      injury itself provides a stimulus for transcription factor activation either
      directly due to mechanical stress, or via paracrine mechanisms such as the
      release of growth factors from damaged cells. Members of the activator protein-1
      family, in particular c-fos and c-jun, have been the most widely studied wound
      induced transcription factors. The signal transduction pathways linking cellular
      injury to activator protein-1 stimulation appear to involve an increase in
      intracellular Ca2+ and activation of mitogen-activated protein kinases. Given
      that a number of genes involved in the reepithelialization of wounds are
      regulated by activator protein-1, a distinct role for this transcription factor
      in reepithelialization is beginning to emerge. This article reviews the evidence
      for activator protein-1 involvement in reepithelialization, with particular focus
      on the activation of this transcription factor in response to wounding, the
      second messenger/kinase pathways involved, and the modulation of downstream genes
      that have the capacity to regulate keratinocyte function.

PMID- 11983003
TI  - Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment
      of diabetic foot ulcers.
AB  - Proteases play a critical role in many of the physiologic processes of wound
      repair. However, if their activity becomes uncontrolled proteases can mediate
      devastating tissue damage and consequently they have been implicated in chronic
      wound pathophysiology. Previous studies have shown that chronic wound fluid
      contains elevated protease levels that have deleterious effects, degrading de
      novo granulation tissue and endogenous biologically active proteins such as
      growth factors and cytokines. Therefore, we have proposed that an effective
      therapeutic approach for chronic wounds would be to modify this hostile
      environment and redress this proteolytic imbalance. Using an ex vivo wound fluid
      model, we show the ability of a proprietary new wound treatment to bind and
      inactivate proteases. We have shown that the addition of this test material to
      human chronic wound fluid obtained from diabetic foot ulcer patients resulted in
      a significant reduction in the activities of neutrophil-derived elastase,
      plasmin, and matrix metalloproteinase when compared to wet gauze. This study
      provides mechanistic evidence to support the hypothesis that this novel treatment
      modality for chronic wounds physically modifies the wound microenvironment, and
      thereby promotes granulation tissue formation and stimulates wound repair.

PMID- 11983004
TI  - Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix
      metalloproteinase-1 in wound fluids are inversely correlated with healing of
      pressure ulcers.
AB  - Previous analyses of fluids collected from chronic, nonhealing wounds found
      elevated levels of inflammatory cytokines, elevated levels of proteinases, and
      low levels of growth factor activity compared with fluids collected from acute,
      healing wounds. This led to the general hypothesis that chronic inflammation in
      acute wounds produces elevated levels of proteinases that destroy essential
      growth factors, receptors, and extracellular matrix proteins, which ultimately
      prevent wounds from healing. To test this hypothesis further, pro- and activated
      matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of
      metalloproteinases (TIMP-1 and TIMP-2), and the ratios of MMPs/TIMPs were assayed
      in fluids and biopsies collected from 56 patients with chronic pressure ulcers.
      Specimens included ulcers treated for 0, 10, and 36 days with conventional
      therapy or with exogenous cytokine therapies. Quantitative assay data were
      correlated with the amount of healing. The average MMP-9/TIMP-1 ratio in fluids
      from 56 ulcers decreased significantly as the chronic pressure ulcers healed.
      Furthermore, the average MMP-9/TIMP-1 ratio was significantly lower for fluids
      collected on day 0 from wounds that ultimately healed well (> or =85% reduction
      in initial wound volume) compared with wounds that healed poorly (< 50% wound
      volume reduction). These data show that the ratio of MMP-9/TIMP-1 levels is a
      predictor of healing in pressure ulcers and they provide additional support for
      the hypothesis that high levels of MMP activity and low levels of MMP inhibitor
      impair wound healing in chronic pressure ulcers.

PMID- 11983005
TI  - Chemically modified tetracycline (CMT-8) and estrogen promote wound healing in
      ovariectomized rats: effects on matrix metalloproteinase-2, membrane type 1
      matrix metalloproteinase, and laminin-5 gamma2-chain.
AB  - Estrogen deficiency is associated with impaired cutaneous wound healing.
      Remodeling of the extracellular matrix in wound healing involves the action of
      matrix metalloproteinases on basement membrane zone components, especially
      laminin-5. We studied the effects of estrogen and a potent matrix
      metalloproteinase inhibitor, chemically modified non-antimicrobial tetracycline,
      CMT-8, on wound healing in ovariectomized rats. At the tissue level, laminin-5
      gamma2-chain expression was decreased and the migration-inductive 80 kDa form of
      laminin-5 gamma2-chain was absent in ovariectomized rats when compared with sham
      and CMT-8- or estrogen-treated ovariectomized animals as detected by Western
      blotting. The highest levels of gelatinolytic activity (matrix metalloproteinase
      2 and -9) were found in sham animals. Levels were reduced in ovariectomized rats
      and were lowest after treating ovariectomized rats with CMT-8 or estrogen as
      analyzed by functional activity assay and zymography. The total amount of
      membrane type 1-matrix metalloproteinase was unchanged in all groups. We conclude
      that CMT-8 and estrogen can promote wound healing in ovariectomized rats, not
      only by normalizing wound bed total collagen content and structure, but also by
      recovering the expression and processing of key molecules in wound healing, i.e.,
      laminin-5 gamma2-chain. This study shows, for the first time, the role of
      estrogen and CMT-8 in laminin-5 gamma2-chain modulation in vivo.

PMID- 11983006
TI  - Role of glutathione redox dysfunction in diabetic wounds.
AB  - We propose that diabetic foot ulcers and diabetic mouse wounds have insufficient
      glutathione to maintain correct cellular redox potential. Therefore, tissue
      samples from the wound edge of diabetic foot ulcers, diabetic mice wounds and
      nondiabetic mice wounds were obtained. Levels of glutathione, cysteine, and mixed
      protein disulfide were determined and topical application of esterified
      glutathione in carboxymethylcellulose or carboxymethylcellulose alone was applied
      to the mice wounds. Diabetic foot ulcer mean glutathione levels were 150.6
      pmol/mg in the controls and 53.4 pmol/mg at the wound edge (p < 0.05), while mean
      cysteine levels were 22.3 pmol/mg in the control and 10.5 pmol/mg at the wound
      edge (p < 0.05). The mixed protein disulfide levels were elevated in the wounds
      (14.6 pmol/mg), but not in the control (6.9 pmol/mg) (p < 0.05). The glutathione
      levels were lower in the diabetic mouse wounds (155 pmol/mg) than the nondiabetic
      mouse wounds (205 pmol/mg) (p=0.04). The diabetic mouse treated with
      carboxymethylcellulose alone healed slower (19.5 +/- 2.2 days) than the
      nondiabetic mouse DM (11.5 +/- 0.5 days) (p < 0.001). The diabetic mouse that
      received topical glutathione healed significantly faster (12.5 +/- 0.8 days) than
      the carboxymethylcellulose-treated mice (19.5 +/- 2.2 days) (p < 0.001).
      Glutathione levels in the diabetic mouse (26.0 pmol/mg) were lower than in the
      nondiabetic mouse (311.7 pmol/mg) (p < 0.05) after glutathione treatment. In the
      glutathione-treated diabetic mouse, the oxidized glutathione was higher (26.7%)
      than in the nondiabetic mouse (9.9%) (p=0.05). These data suggest that cellular
      redox dysfunction and lower glutathione levels are present in diabetic foot
      ulcers and diabetic mouse wounds.

PMID- 11983007
TI  - Transient increase in telomerase activity of proliferating fibroblasts and
      endothelial cells in granulation tissue of the human skin.
AB  - Although granulation tissue formation is an important step for second-intention
      wound healing, the molecular events underlying this process are still poorly
      understood. To investigate the role of telomerase in the formation of granulation
      tissue, we measured the activity of this enzyme and determined the expression and
      localization of human telomerase reverse transcriptase mRNA using human skin
      samples. Telomerase activity in the tip of the granulation tissue where
      fibroblasts actively proliferate was detected at a level 5.6 +/- 1.5 times higher
      than that at the edge of the tissue when using a polymerase chain reaction-based
      telomeric repeat amplification protocol assay coupled with enzyme-linked
      immunosorbent assay. This, together with the findings from semiquantitative
      reverse transcriptase-polymerase chain reaction and in situ hybridization of
      human telomerase reverse transcriptase, revealed that proliferating cell nuclear
      antigen-positive fibroblasts and endothelial cells in the progressing granulation
      tissue showed de novo activation of telomerase with high human telomerase reverse
      transcriptase mRNA expression. This condition may be a prolongation of cellular
      replicative capacity taking advantage of the positive regulatory dynamics of cell
      growth. We conclude that the regulation of telomerase activity may play an
      important role in granulation tissue formation in wound healing.

PMID- 11983008
TI  - Epidermal growth factor induces acute matrix contraction and subsequent calpain
      modulated relaxation.
AB  - During wound healing, dermal fibroblasts switch from a migratory, repopulating
      phenotype to a contractile, matrix-reassembling phenotype. The mechanisms
      controlling this switch are unknown. A possible explanation is suggested by the
      finding that chemokines that appear late in wound repair prevent growth factor
      induced cell-substratum de-adhesion by blocking calpain activation. In this
      study, we tested the specific hypothesis that fibroblast contraction of the
      matrix is promoted by a pro-repair growth factor, epidermal growth factor, and is
      modulated by calpain-mediated release of adhesions. We employed an isometric
      force transduction system designed to measure the contraction of a collagen
      matrix under tension by a population of NR6 fibroblasts transfected with the
      human epidermal growth factor receptor. By maintaining a fixed level of strain,
      we could monitor both the initial contraction and subsequent relaxation of the
      matrix. Epidermal growth factor stimulated a transient, dose-dependent increase
      in matrix contraction that peaked within 60 minutes and then decayed over the
      ensuing 3 to 6 hours. Calpain inhibitor I (ALLN) prevented epidermal growth
      factor-stimulated cell de-adhesion and resulted in a significantly slower decay
      of matrix contraction, with only a slight decrease of the peak magnitude of
      contraction. The mitogen-activated protein kinase kinase-1-selective inhibitor PD
      98059 that blocks signaling through the extracellular signal-regulated
      kinase/mitogen-activated protein kinase pathway, required for epidermal growth
      factor receptor-mediated activation of calpain and de-adhesion, does not
      significantly affect the magnitude of matrix contraction within minutes of
      epidermal growth factor addition, but slows the decay similarly to calpain
      inhibition. Epidermal growth factor receptor signaling thus stimulates the
      complementary mechanisms of intracellular contractile force generation and
      calpain-mediated de-adhesion, which are known to coordinately facilitate cell
      migration. These findings suggest that calpain can act as a functional switch for
      transmission of intracellular contractile force to the surrounding matrix, with
      calpain-mediated de-adhesion reducing this transmission and corresponding matrix
      contraction. Countervailing processes that down-regulate calpain activation can,
      accordingly, direct the transition of cell function from locomotion to matrix
      contraction.

PMID- 11983009
TI  - Changes in serum levels of apolipoprotein A-1 as an indicator of protein
      metabolism after hepatectomy.
AB  - The clinical significance of serum apolipoprotein A-1 levels as an indicator of
      hepatic protein synthesis after hepatectomy was investigated. A total of 50
      patients who had undergone hepatectomy at our department from 1997 to 1999 were
      selected for this study. The serum levels of apolipoprotein A-1, indocyanine
      green dye retention at 15 minutes, lectin-cholesterol acyltransferase,
      prealbumin, and high-density lipoprotein cholesterol were measured in these
      patients preoperatively and on postoperative days 7 and 14. The type of hepatic
      resection conducted was partial resection in 13 cases, subsegmentectomy in 13
      cases, segmentectomy in five cases, and bisegmentectomy in 19 cases. All the
      patients tolerated the operation, and none of the cases had any severe
      complications, such as liver failure. In most cases, the serum apolipoprotein A-1
      levels decreased on postoperative day 7 and recovered by day 14. There were no
      significant differences in the changes in apolipoprotein A-1 levels between
      patients with the individual types of operative procedures. The serum
      apolipoprotein A-1 levels showed significant correlations with the serum high
      density lipoprotein cholesterol, lectin-cholesterol acyltransferase and
      prealbumin levels on postoperative days 7 and 14; however, there was no
      significant correlation with the indocyanine green retention test. When the cases
      were divided into three groups according to the serum level of apolipoprotein A-1
      on postoperative day 7 (group A: over 81 mg/dl, group B: 61-80 mg/dl, group C:
      under 60 mg/dl), the serum indocyanine green retention, prealbumin, lectin
      cholesterol acyltransferase and high-density lipoprotein cholesterol levels in
      group C were significantly lower than those in group A on postoperative day 7. On
      the basis of these results, it is suggested that the pattern of changes in the
      serum apolipoprotein A-1 levels may be a good indicator of the hepatic protein
      synthetic ability during the perioperative period after hepatectomy.

PMID- 11983012
TI  - Genetic modification of pigs by nuclear transfer.

PMID- 11983013
TI  - Pontifica Academia proVita, prospects for xenotransplantation: scientific aspects
      and ethical considerations (Vatican City, 2001): a critical review.

PMID- 11983014
TI  - Production of human monoclonal antibodies against Galalpha(1-3)Gal.
AB  - The hyperacute rejection observed in models of pig-to-human xenotransplantation
      is mainly because of the presence of natural antibodies in human blood with
      specificity for the Galalpha(1-3)Gal (Gal) carbohydrate moiety present on the
      surface of porcine endothelial cells. Human monoclonal anti-Gal antibodies could
      be of use both in the study of the basic mechanisms of hyperacute rejection as
      well as in its clinical prevention. In the present study we prepared 42
      heterohybridomas (human-mouse) secreting antibodies with specificity for the Gal
      epitope. All of the antibodies produced were of the IgM isotype, according to a
      dot-blot assay. Twenty-seven antibodies were further characterized, and shown to
      be specific for Gal by different methods, including an enzyme-linked
      immunosorbent assay, in which the plates were sensitized with mouse laminin as a
      source of Gal. Specificity was also confirmed using purified Gal carbohydrate in
      a hemagglutination inhibition assay. The antibodies were shown to mediate lysis
      of Gal-expressing rabbit erythrocytes in the presence of complement. However, the
      heterohybridomas themselves were shown to express Gal, a result of the mouse
      P3x63Ag8.653 hybridoma cells used during hybridoma generation. The presence of
      this epitope on the surface of anti-Gal-producing cells, and on the antibody
      itself, represents a limitation to the production of high affinity anti-Gal
      antibodies.

PMID- 11983015
TI  - Host systemic and local nitric oxide levels do not correlate with rejection of
      pig proislet xenografts in mice.
AB  - The rejection of pig proislet xenografts in mice is a CD4 T cell-dependent
      process in which macrophages play an important role. To assess the potential for
      activated macrophages to act as effector cells in xenograft destruction, we have
      examined the relationship between proislet xenograft rejection, two principal
      markers of macrophage activation, transcription of inducible nitric oxide
      synthase (iNOS) and production of nitric oxide (NO), and their temporal
      relationship to intragraft cytokine gene expression. Xenograft rejection in CBA/H
      mice correlated with early induction of intragraft host iNOS mRNA and marked
      intragraft production of NO (reactive nitrogen intermediates, RNI). Intragraft
      mRNA expression for IFN-gamma, IL-1beta and TNF, cytokines associated with
      macrophage activation, was also found. These findings suggested that activated
      macrophages could be contributing to xenograft destruction via local NO-mediated
      toxicity at the graft site. To test the role of NO in this model: (1) Q-fever
      antigen (QFA) was administered to recipient mice in order to induce high systemic
      RNI levels and (2) in another experiment, pig proislets were transplanted into
      iNOS-/- mice. Treatment with QFA correlated with prolonged xenograft survival at
      7 days post-transplant. Splenocytes from QFA-treated, but not control mice at 7
      and 22 days post-transplant, exhibited inhibition of secondary xenogeneic mouse
      antiporcine mixed lymphocyte reaction (MLR) that was reversed by culture with the
      NOS inhibitor N-methylarginine (NMA). Despite continued elevated NO production,
      xenograft protection was temporary with complete rejection by day 22. Evidence
      that locally produced NO was not contributing to rejection was seen when pig
      proislets transplanted into iNOS-/- mice were rejected with normal kinetics; in
      these animals intragraft NO production was not detected (despite porcine iNOS
      gene expression). Failure of activated macrophages to achieve indefinite
      xenograft survival suggests that other factors are also required. Macrophage
      potential to effect either destructive or protective roles after pig proislet
      xenotransplantation suggests that such functions may depend on the site and
      magnitude of macrophage activation. Together these findings clearly demonstrate
      that high NO levels in the periphery are not damaging to xenogeneic islet tissue,
      neither host nor donor NO production is essential for islet xenograft rejection
      and consequently elevated plasma RNI levels do not represent a direct marker for
      rejection.

PMID- 11983016
TI  - Production and characterization of a pig line transgenic for human membrane
      cofactor protein.
AB  - A pig line transgenic for human membrane cofactor protein (hMCP) has been
      established. Offspring from the founder were produced by crossing the founder
      with pigs heterozygous for the human decay accelerating factor (hDAF) transgene.
      As a result, pigs transgenic for both hMCP and hDAF have been produced.
      Ribonuclease protection assay (RPA) indicated that hMCP was expressed in all the
      tissues analysed. In addition, immunohistochemical results indicated a high level
      of expression of hMCP on neural tissues and islets where hDAF was absent or
      weakly expressed. C3 fragment deposition and cytotoxicity assays indicated that
      hMCP expression alone on pig endothelial cells and peripheral blood lymphocytes
      (PBLs) provided protection against human complement mediated damage. However, we
      did not find that porcine endothelial cells expressing both hDAF and hMCP were
      better protected than those expressing hDAF alone. The expression of hMCP on
      tissues where hDAF is not expressed could provide these tissues with protection
      against human complement mediated lysis.

PMID- 11983017
TI  - The production of transgenic pigs for potential use in clinical
      xenotransplantation: microbiological evaluation.
AB  - Debate over the infection hazards of pig-to-human xenotransplantation has focused
      mainly on the porcine endogenous retroviruses (PERV). However, hazards of
      exogenous infectious agents possibly associated with the xenograft have also been
      evaluated (Xenotransplantation 2000; 7: 143). We report the results of a health
      monitoring program demonstrating the exclusion of more than 80 potential
      pathogens from nine cohorts of pigs reared in a high welfare bioexclusion
      facility as potential xenograft source animals. A dynamic bacterial flora of pigs
      reared under barrier conditions was characterized, emphasizing the significance
      of monitoring for multiresistant antimicrobial sensitivity patterns. Evidence was
      found for exclusion of two commonly residual exogenous viruses, porcine
      cytomegalovirus and porcine lymphotropic herpesviruses, among a proportion of the
      cohorts tested. Finally, there was histopathological evidence for low grade
      pneumonitis among sentinel pigs, likely to have been associated with the use of
      quaternary ammonium disinfectants during the production process, indicating a
      need for review of toxicology data for disinfectant agents used in such
      bioexclusion systems. Intensive health monitoring programs, based upon regularly
      updated recommendations from the microbiological research community, will enable
      significant reductions in the potential hazards associated with pig-to-human
      xenotransplantation.

PMID- 11983018
TI  - The production of transgenic pigs for potential use in clinical
      xenotransplantation: baseline clinical pathology and organ size studies.
AB  - This report describes the results of hematology, serum biochemistry, growth, and
      organ weight studies undertaken on pigs from nine cohorts of qualified pathogen
      free (QPF) pigs reared within a high welfare bioexclusion facility as potential
      organ source animals. Confirmation of the high health status of the pigs was
      given through total leukocyte counts and serum globulin concentrations that fell
      below the expected reference range for conventional pigs. The calculated mean
      growth rate for QPF pigs was found to exceed target rates set for optimum
      genotype commercial pig herds. Body weights of QPF pigs were compared with
      kidney, heart and liver weights at necropsy.

PMID- 11983019
TI  - Isolation of mouse-to-rat cardiac xenograft-infiltrating cells by ex vivo
      propagation.
AB  - Ex vivo propagation of graft infiltrating lymphocytes has become a useful method
      for the examination of the cellular response after allogeneic transplantation.
      The aim of the present study was to investigate if this method can be used also
      for isolation of xenograft infiltrating cells, and, if so, to further
      characterize these cells. The concordant mouse-to-rat heart transplantation model
      was used for the experiments. Recipient rats were treated either with 15
      deoxyspergualin (DSG) or with a combination of DSG and cyclosporine A (CyA) or
      left untreated. Transplants were removed beating on day 2 (untreated) or day 8
      (DSG and CyA + DSG) and biopsies were incubated in culture medium for 48 h,
      resulting in propagation of cells from the biopsies into culture medium. The
      propagated cells were counted and phenotyped using flow cytometry. In parallel,
      the transplants were examined morphologically and immunohistochemically.
      Infiltrating cells could be isolated from all grafts in all groups. The number of
      propagated T lymphocytes during cellular rejection (DSG-treatment) was about 3.5
      times higher than during 'non-rejection' (CyA + DSG) and six times higher than
      during acute vascular rejection (untreated). These findings were supported both
      by the morphological and the immunohistochemical findings. In conclusion, we have
      shown that graft infiltrating lymphocytes can be isolated from xenogeneic heart
      transplants by incubation of biopsies for 48 h, resulting in spontaneous
      propagation of immune cells into culture medium. Propagated cells could be
      further characterized by flow cytometry. Thus, the technique presented here can
      be used as a tool for studies of xenogeneic cellular rejection.

PMID- 11983020
TI  - Pig peripheral blood mononuclear cells are directly associated with the
      thrombotic microangiopathy that complicates the induction of chimerism in pig-to
      baboon xenotransplantation.
AB  - The infusion of large numbers of porcine cells into primates in order to induce
      specific immunologic tolerance by mixed hematopoietic chimerism, results in
      thrombotic microangiopathy that can be fatal. For this reason, it is important to
      study in vitro the interaction of primate endothelial cells with pig cells. We
      show that pig peripheral blood mononuclear cells (p-PBMC) activate human
      endothelial cells (hECs) through direct contact. Thus, when endothelial cells are
      cultured in the presence of p-PBMC, overexpression of VCAM-1 and E-selectin
      adhesion molecules occurs within 3 h of culture and continues for at least 9 h.
      The co-culture of p-PBMC and hECs also results in an important adhesion of human
      platelets to both types of cell. Thus, viewed with the microscope, platelets
      aggregate above the endothelial cells and also around the pig cells. We present
      data that suggest that the presence of p-PBMC may be more important with regard
      to the increase of platelet adhesion to the endothelial cells than the activation
      alone of the cells. Our results also show that p-PBMC, and not the activated
      endothelia or the culture supernatant of activated hECs, are able to activate the
      coagulation cascade because they are able to generate thrombin when added to
      defibrinated human plasma. Overall, these findings suggest that p-PBMC are of
      primary importance for the development of the thrombotic disorders that occur in
      primates transplanted with pig progenitor cells.

PMID- 11983021
TI  - Enzymatic removal of alphaGal antigen in pig kidneys by ex vivo and in vivo
      administration of endo-beta-galactosidase C.
AB  - Xenotransplantation using the pig as a donor species is considered to be a
      promising solution to the serious shortage of organ donors. Both hyperacute and
      acute vascular rejection (AVR) are believed to be associated with xenoreactive
      antibody binding to alphaGal epitopes on the pig vascular endothelial cells.
      Thus, suppression of this antigen-antibody reaction would appear essential for
      successful long-term xenograft survival. The purpose of this study was to examine
      the efficacy of ex vivo and in vivo administration of recombinant endo-beta
      galactosidase C (EndoGalC which, in previous in vitro studies, has been proven to
      digest alphaGal antigens completely) on alphaGal epitopes expressed in pig
      kidneys. Excised pig kidneys were perfused with University of Wisconsin solution
      containing EndoGalC and preserved for 4 h. After cold storage, the pig kidney was
      transplanted into another pig. Ex vivo perfusion and cold storage with EndoGalC
      reduced alphaGal epitope expression on vascular endothelial cells to an
      undetectable level. However, alphaGal antigens began to be expressed again as
      early as 1 day after transplantation. The digestion of alphaGal epitopes by
      EndoGalC did not cause any damage to the kidney graft. EndoGalC was intravenously
      administered to two pigs (15 kg), without causing any serious adverse effect.
      Twelve hours later, >98% of alphaGal antigens on pig red blood cells (RBCs) had
      been digested. Immunohistochemical study revealed almost complete elimination of
      alphaGal expression on vascular endothelial cells of the kidney graft 4 and 8 h
      after in vivo administration, but reappearance within 24 h. EndoGalC was
      administered to a baboon after an interval of 2 months. The second administration
      did not result in any serious toxicity or reduction in efficacy. These results
      suggest that ex vivo and in vivo administration of EndoGalC is simple and useful
      in removing alphaGal epitopes from pig organs. As the effect of EndoGalC is
      temporary, multiple in vivo administrations of EndoGalC would be required to
      inhibit the reappearance of alphaGal epitopes. Alternatively, transgenic
      techniques of introducing the gene for EndoGalC into the donor organ might
      permanently prevent alphaGal expression.

PMID- 11983023
TI  - Comparison of an immortalized human corneal epithelial cell line with Vero cells
      in the isolation of Herpes simplex virus-1 for the laboratory diagnosis of Herpes
      simplex keratitis.
AB  - BACKGROUND: Herpes simplex keratitis (HSK) is a sight threatening ocular
      infection often requiring a specific and prompt laboratory diagnosis. Isolation
      of Herpes simplex virus (HSV-1) in culture provides the most reliable and
      specific method and is considered as the "Gold Standard" in the laboratory
      diagnosis of HSK in spite of its low sensitivity. Using "cell lines of corneal
      origin" for virus isolation may be beneficial under such circumstances, since
      these cells have been shown to be excellent substrates for the growth of HSV-1
      isolated from the cornea. We report a comparative study of a novel human corneal
      epithelial cell line (HCE) and the Vero cell line in the isolation of HSV-1 from
      corneal scrapings employing a shell vial assay. METHODS: Corneal scrapings were
      obtained from 17 patients with a clinical diagnosis of HSK. All the cases were
      confirmed by virological investigations (PCR and viral antigen detection
      positive, n = 15, PCR positive, n = 1, Viral antigen positive, n = 1). Scrapings
      obtained from 10 patients with infectious keratitis of non-viral origin were
      included as controls. All the scrapings were simultaneously inoculated into shell
      vials of HCE and Vero cells. Cultures were terminated at 24 h post-infection.
      Isolation of HSV-1 was confirmed using an indirect immunofluorescence/
      immunoperoxidase assay. RESULTS: Virus could be isolated using both or either of
      the cell lines in 10/17 (58.82%) patients with HSK. HSV-1 was isolated from 10/17
      (58.82%) and 4/17(23.52%) specimens in HCE and Vero cells, respectively (P =
      0.036). None of the controls yielded HSV-1. While all the 10 (100%) strains were
      isolated in HCE, Vero yielded only 4/10 (40%) strains in the shell vial culture
      (P = 0.014). CONCLUSIONS: HCE showed a statistically significant difference in
      the virus isolation rate with respect to Vero cells. HCE may be an excellent
      alternative cell line for the isolation of HSV-1, especially from corneal
      scrapings, for the laboratory diagnosis of HSK.

PMID- 11983022
TI  - Anti-HIV-1 activity of cellulose acetate phthalate: synergy with soluble CD4 and
      induction of "dead-end" gp41 six-helix bundles.
AB  - BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide
      for prevention of sexual transmission of the human immunodeficiency virus type 1
      (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to
      inactivate HIV-1 and to block the coreceptor binding site on the virus envelope
      glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is
      the primary cellular receptor for HIV-1, it was of interest to study CAP binding
      to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including
      changes in the conformation of the envelope glycoprotein gp41 within virus
      particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study
      CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles
      accessible on virus particles using antibodies specific for the alpha-helical
      core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments
      subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for
      inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the
      formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct
      sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound
      effects on virus structure and infectivity. The formation of gp41 six-helical
      bundles, induced by CAP, is known to render the virus incompetent for fusion with
      target cells thus preventing infection.

PMID- 11983024
TI  - Paediatric referrals in rural Tanzania: the Kilombero District Study - a case
      series.
AB  - BACKGROUND: Referral is a critical part of appropriate primary care and of the
      Integrated Management of Childhood Illness (IMCI) strategy. We set out to study
      referrals from the aspect both of primary level facilities and the referral
      hospital in Kilombero District, southern Tanzania. Through record review and a
      separate prospective study we estimate referral rates, report on delays in
      reaching referral care and summarise the appropriateness of pediatric referral
      cases in terms of admission to the pediatric ward at a district hospital METHODS:
      A sample of patient records from primary level government health facilities
      throughout 1993 were summarised by age, diagnosis, whether a new case or a
      reattendance, and whether or not they were referred. From August 1994 to July
      1995, mothers or carers of all sick children less than five years old attending
      the Maternal and Child Health (MCH) clinic or outpatient department (OPD) of
      SFDDH were interviewed using a standard questionnaire recording age, sex,
      diagnosis, place of residence, whether the child was admitted to the paediatric
      ward, and whether the child was referred. RESULTS: From record review, only 0.6%
      of children from primary level government facilities were referred to a higher
      level of care. At the referral hospital, 7.8 cases per thousand under five
      catchment population had been referred annually. The hospital MCH clinic and OPD
      were generally used by children who lived nearby: 91% (n = 7,166) of sick
      children and 75% (n = 607) of admissions came from within 10 km. Of 235 referred
      children, the majority (62%) had come from dispensaries. Almost half of the
      referrals (48%) took 2 or more days to arrive at the hospital. Severe malaria and
      anaemia were the leading diagnoses in referred children, together accounting for
      a total of 70% of all the referrals. Most referred children (167/235, 71%) were
      admitted to the hospital paediatric ward. CONCLUSIONS: The high admission rate
      among referrals suggests that the decision to refer is generally appropriate, but
      the low referral rate suggests that too few children are referred. Our findings
      suggest that the IMCI strategy may need to be adapted in sparsely-populated areas
      with limited transport, so that more children may be managed at peripheral level
      and fewer children need referral.

PMID- 11983025
TI  - Mitotic death: a mechanism of survival? A review.
AB  - Mitotic death is a delayed response of p53 mutant tumours that are resistant to
      genotoxic damage. Questions surround why this response is so delayed and how its
      mechanisms serve a survival function. After uncoupling apoptosis from G1 and S
      phase arrests and adapting these checkpoints, p53 mutated tumour cells arrive at
      the G2 compartment where decisions regarding survival and death are made. Missed
      or insufficient DNA repair in G1 and S phases after severe genotoxic damage
      results in cells arriving in G2 with an accumulation of point mutations and
      chromosome breaks. Double strand breaks can be repaired by homologous
      recombination during G2 arrest. However, cells with excessive chromosome lesions
      either directly bypass the G2/M checkpoint, starting endocycles from G2 arrest,
      or are subsequently detected by the spindle checkpoint and present with the
      features of mitotic death. These complex features include apoptosis from
      metaphase and mitosis restitution, the latter of which can also facilitate
      transient endocycles, producing endopolyploid cells. The ability of cells to
      initiate endocycles during G2 arrest and mitosis restitution most likely reflects
      their similar molecular environments, with down-regulated mitosis promoting
      factor activity. Resulting endocycling cells have the ability to repair damaged
      DNA, and although mostly reproductively dead, in some cases give rise to mitotic
      progeny. We conclude that the features of mitotic death do not simply represent
      aberrations of dying cells but are indicative of a switch to amitotic modes of
      cell survival that may provide additional mechanisms of genotoxic resistance.

PMID- 11983026
TI  - Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human
      b lymphoma cell line bl36.
AB  - BACKGROUND: 5-AzaCytidine (AzaC) is a DNA demethylating drugs that has been shown
      to inhibit cell growth and to induce apoptosis in certain cancer cells. Induced
      expression of the galectin1 (Gal1) protein, a galactoside-binding protein
      distributed widely in immune cells, has been described in cultured hepatoma
      derived cells treated with AzaC and this event may have a role in the effect of
      the drug. According to this hypothesis, we investigated the effect of AzaC and
      Gal1 on human lymphoid B cells phenotype. METHODS: The effect of AzaC and Gal1 on
      cell growth and phenotype was determined on the Burkitt lymphoma cell line BL36.
      An immunocytochemical analysis for detection of Gal1 protein expression was
      performed in AzaC-treated cells. To investigate the direct effects of Gal1,
      recombinant Gal1 was added to cells. RESULTS: Treatment of lymphoid B cells with
      AzaC results in: i) a decrease in cell growth with an arrest of the cell cycle at
      G0/G1 phase, ii) phenotypic changes consistent with a differentiated phenotype,
      and iii) the expression of p16, a tumor-suppressor gene whose expression was
      dependent of its promoter demethylation, and of Gal1. A targeting of Gal 1 to the
      plasma membrane follows its cytosolic expression. To determine which of the
      effects of AzaC might be secondary to the induction of Gal1, recombinant Gal1 was
      added to BL36 cells. Treated cells displayed growth inhibition and phenotypic
      changes consistent with a commitment toward differentiation. CONCLUSIONS: Altered
      cell growth and expression of the cell surface plasma cell antigen, CD138 are
      detectable in BL36 cells treated by AzaC as well as by Gal1. It seems that AzaC
      induced Gal1 expression and consequent binding of Gal1 on its cell membrane
      receptor may be, in part, involved in AzaC-induced plasmacytic differentiation.

PMID- 11983027
TI  - Role of arginine and its methylated derivatives in cancer biology and treatment.
AB  - Both L-arginine supplementation and deprivation influence cell proliferation. The
      effect of high doses on tumours is determined by the optical configuration: L
      arginine is stimulatory, D-arginine inhibitory. Arginine-rich hexapeptides
      inhibited tumour growth. Deprivation of L-arginine from cell cultures enhanced
      apoptosis. The pro-apoptotic action of NO synthase inhibitors, like NG-monomethyl
      L-arginine, is manifested through inhibition of the arginase pathway. NG
      hydroxymethyl-L-arginines caused apoptosis in cell cultures and inhibited the
      growth of various transplantable mouse tumours. These diverse biological
      activities become manifest through formaldehyde (HCHO) because guanidine group of
      L-arginine in free and bound form can react rapidly with endogenous HCHO, forming
      NG-hydroxymethylated derivatives. L-arginine is a HCHO capturer, carrier and
      donor molecule in biological systems. The role of formaldehyde generated during
      metabolism of NG-methylated and hydroxymethylated arginines in cell proliferation
      and death can be shown. The supposedly anti-apoptotic homozygous Arg 72-p53
      genotype may increase susceptibility of some cancers. The diverse biological
      effects of L-arginine and its methylated derivatives call for further careful
      studies on their possible application in chemoprevention and cancer therapy.

PMID- 11983028
TI  - Retroviral transfer of the p16INK4a cDNA inhibits C6 glioma formation in Wistar
      rats.
AB  - BACKGROUND: The p16INK4A gene product halts cell proliferation by preventing
      phosphorylation of the Rb protein. The p16INK4a gene is often deleted in human
      glioblastoma multiforme, contributing to unchecked Rb phosphorylation and rapid
      cell division. We show here that transduction of the human p16INK4a cDNA using
      the pCL retroviral system is an efficient means of stopping the proliferation of
      the rat-derrived glioma cell line, C6, both in tissue culture and in an animal
      model. C6 cells were transduced with pCL retrovirus encoding the p16INK4a, p53,
      or Rb genes. These cells were analyzed by a colony formation assay. Expression of
      p16INK4a was confirmed by immunohistochemistry and Western blot analysis. The
      altered morphology of the p16-expressing cells was further characterized by the
      senescence-associated beta-galactosidase assay. C6 cells infected ex vivo were
      implanted by stereotaxic injection in order to assess tumor formation. RESULTS:
      The p16INK4a gene arrested C6 cells more efficiently than either p53 or Rb.
      Continued studies with the p16INK4a gene revealed that a large portion of
      infected cells expressed the p16INK4a protein and the morphology of these cells
      was altered. The enlarged, flat, and bi-polar shape indicated a senescence-like
      state, confirmed by the senescence-associated beta-galactosidase assay. The
      animal model revealed that cells infected with the pCLp16 virus did not form
      tumors. CONCLUSION: Our results show that retrovirus mediated transfer of
      p16INK4a halts glioma formation in a rat model. These results corroborate the
      idea that retrovirus-mediated transfer of the p16INK4a gene may be an effective
      means to arrest human glioma and glioblastoma.

PMID- 11983029
TI  - Toll-like receptors: the key to the stable door?
AB  - Severe sepsis continues to lead to critical illness. Few therapeutic options
      exist other than antibiotic therapy and general supportive care. Large numbers of
      patients continue to die as a consequence of overactivation of the host
      inflammatory response and the resultant coagulopathy and disregulation of the
      normal controls of vasoactive tone. It is now known that a critical part of this
      host response occurs at the level of innate defence, without the need for antigen
      processing or the clonal expansion of cells targeted against the invading
      pathogen. This commentary will discuss the therapeutic targets revealed by our
      new understanding of the Toll-like receptor. The potential clinical difficulties
      that may result from intervention at this pattern-recognition receptor will also
      be explored.

PMID- 11983030
TI  - Insulin: a wonder drug in the critically ill?
AB  - Stress hyperglycaemia is a common event in acute critical illness. There is
      increasing evidence that maintaining normoglycaemia and treatment with insulin
      (or with glucose-insulin-potassium [GIK]), even in non-diabetic persons, is
      helpful in limiting organ damage after myocardial infarction, stroke, traumatic
      brain injury and other conditions, even though the conditions may be accompanied
      by insulin resistance. A landmark study now suggests that maintaining
      normoglycaemia with intensive insulin treatment in a heterogeneous population of
      critically ill patients decreases morbidity and mortality. The potential
      mechanisms that underlie such a beneficial effect are discussed.

PMID- 11983031
TI  - Infective endocarditis: too ill to be operated?
AB  - Infective endocarditis remains a disease associated with high mortality in
      certain groups of patients, with death resulting primarily from central nervous
      system complications and congestive heart failure. Combined medical and surgical
      therapy reduces both early and late mortality in complicated cases, especially in
      patients with valvular dysfunction related to heart failure. In these patients,
      heart failure is the strongest indication for valve replacement. There are no
      consensus indications for surgery, however, in the presence of neurological
      complications or multiple organ failure. Limited data suggest that such surgery
      is feasible, even in complicated cases necessitating admission to the intensive
      care unit, and carries an acceptable risk for in-hospital mortality. It is
      important that critically ill patients with infective endocarditis are enrolled
      into multicenter studies, using adequate severity scoring systems to assess the
      impact of clinical and imaging variables on patients' outcome. Until such data
      are obtained, clinical judgement is still the best tool in decision-making
      regarding the individual patient.

PMID- 11983032
TI  - Acetaminophen poisoning: an update for the intensivist.
AB  - Acetaminophen overdose is common and can result from deliberate/nonstaggered or
      accidental/staggered ingestion. Patients presenting within 24 h of an
      acetaminophen overdose can safely be managed on medical wards. Early management
      of nonstaggered overdose is guided by the plasma acetaminophen concentration,
      whereas management of accidental/staggered ingestion is guided by ingested dose.
      Ingested dose and time from ingestion to presentation are important prognostic
      factors in accidental/staggered ingestion. Acetaminophen-induced acute liver
      failure (ALF) requires meticulous supportive care in an intensive care unit
      (ICU), with early identification and transfer of patients who are likely to
      require liver transplantation to a specialist liver centre. The modified King's
      College Hospital criteria (incorporating lactate into the traditional criteria)
      represent the best tool for identifying patients who require transplantation.

PMID- 11983033
TI  - Do bronchodilators have an effect on bronchiolitis?
AB  - Over the past 12 years there have been 12 randomised control trials, involving
      843 infants, evaluating the effect of salbutamol or albuterol on bronchiolitis.
      Of these, nine (75%) showed that bronchodilators had no effect. In three studies
      a small transient improvement in the acute clinical score was seen. Ipratropium
      bromide had no significant effect. There have been five recent randomised trials
      involving 225 infants, evaluating the effect of nebulised adrenaline
      (epinephrine) on bronchiolitis. All five (100%) have shown significant clinical
      improvement, with reductions in oxygen requirement, respiratory rate and wheeze
      after nebulised adrenaline. Two showed lower hospital admission rates and earlier
      discharge with adrenaline. A significant improvement in pulmonary resistance was
      observed after nebulised adrenaline but not after salbutamol or albuterol.
      Currently there is no compelling evidence that bronchodilators have a role in the
      routine management of infants with bronchiolitis. There is better evidence for
      the use of nebulised adrenaline.

PMID- 11983034
TI  - Pro/con clinical debate: are steroids useful in the management of patients with
      septic shock?
AB  - Decision-making in the intensive care unit is often very difficult. Although we
      are encouraged to make evidence-based decisions, this may be difficult for a
      number of reasons. To begin with, evidence may not exist to answer the clinical
      question. Second, when there is evidence it may not be applicable to the patient
      in question or the clinician may be reluctant to apply it to the patient based on
      a number of secondary issues such as costs, premorbid condition or possible
      complications. Finally, emotions are often highly charged when caring for
      patients that have a significant chance of death, and care-givers as well as
      families are frequently prepared to take chances on a therapy whose benefit is
      not entirely clear. Steroid use in septic shock is an example of a therapy that
      makes some sense but has conflicting support in the literature. In this issue of
      Critical Care Forum, the two sides of this often heated debate are brought to the
      forefront in an interesting format.

PMID- 11983035
TI  - Pro/con clinical debate: the use of a protected specimen brush in the diagnosis
      of ventilator associated pneumonia.
AB  - Although mechanical ventilation is instituted as a life-saving technique, it may
      lead to complications that can negatively impact on patients' morbidity and/or
      mortality. Ventilator associated pneumonia (VAP) is one such complication that is
      a common challenge to intensivists. Although most experts would agree that early
      'appropriate' antibiotic use is essential in patients who develop VAP, the best
      diagnostic test to guide decision-making is far from clear. One diagnostic test
      that is capable of providing microbiological samples from the lower respiratory
      tree is invasive bronchoscopy with a protected specimen brush. Such a procedure
      has long been available to intensivists and is frequently employed in many
      intensive care units. However, this procedure has associated costs and potential
      complications, and its utility in VAP has been challenged. In this issue of
      Critical Care Forum, the two sides of this debate are brought forward with
      compelling arguments. The authors' arguments should fuel future trials.

PMID- 11983036
TI  - Reviewing the reviewers: the vague accountability of research ethics committees.
AB  - The role of research ethics committees (RECs) is currently strained by increases
      in the number of protocols that are in need of review, the scientific and funding
      complexities of the protocols, and a lack of clear standards for ethics
      assessment. This commentary describes the significance of these strains and calls
      for clarification of reviewer accountability. To maintain or, in many cases, to
      restore public and professional trust in the ethics of human research and in REC
      review of protocols, it is imperative that steps be taken to clarify the
      accountability of RECs and their individual members.

PMID- 11983037
TI  - Intensive care transfers.
AB  - The demand for intensive care has increased relentlessly over the past 30 years.
      It is now regarded as a necessity rather than a luxury. The provision of
      intensive care has lagged behind that demand. Thus, patients who are judged to
      need intensive care when a bed is unavailable are increasingly transferred to
      another hospital for such care. The present commentary discusses intensive care
      transfers and describes a website being trialled in the UK that helps with
      locating available intensive care beds.

PMID- 11983038
TI  - Bench-to-bedside review: Toll-like receptors and their role in septic shock.
AB  - The Toll-like receptors (TLRs) are essential transmembrane signaling receptors of
      the innate immune system that alert the host to the presence of a microbial
      invader. The recent discovery of the TLRs has rapidly expanded our knowledge of
      molecular events that initiate host-pathogen interactions. These functional
      attributes of the cellular receptors provide insights into the nature of pattern
      recognition receptors that activate the human antimicrobial defense systems. The
      fundamental significance of the TLRs in the generation of systemic inflammation
      and the pathogenesis of septic shock is reviewed. The potential clinical
      implications of therapeutic modulation of these recently characterized receptors
      of innate immunity are also discussed.

PMID- 11983039
TI  - Clinical review: status epilepticus.
AB  - Status epilepticus (SE) has an annual incidence exceeding 100,000 cases in the
      United States alone, of which more than 20% result in death. Thus, increased
      awareness of presentation, etiologies, and treatment of SE is essential in the
      practice of critical care medicine. This review discusses current definitions of
      SE, as well as its clinical presentation and classification. The recent
      literature on epidemiology is reviewed, including morbidity and mortality data.
      An overview of the systemic pathophysiologic effects of SE is presented. Finally,
      significant studies on the treatment of acute SE and refractory SE are reviewed,
      including the use of anticonvulsants, such as benzodiazepines, and other drugs.

PMID- 11983040
TI  - Statistics review 2: samples and populations.
AB  - The previous review in this series introduced the notion of data description and
      outlined some of the more common summary measures used to describe a dataset.
      However, a dataset is typically only of interest for the information it provides
      regarding the population from which it was drawn. The present review focuses on
      estimation of population values from a sample.

PMID- 11983041
TI  - Complicated infective endocarditis necessitating ICU admission: clinical course
      and prognosis.
AB  - AIM: To study incidence, clinical course and prognostic factors in patients
      admitted to medical intensive care units (ICUs) because of a complicated course
      of infective endocarditis. METHOD: This was a retrospective multicenter
      observational study of 4106 patients admitted to four medical ICUs in one
      tertiary hospital and one university hospital between 1994 and 1999. RESULTS:
      Infective endocarditis was identified in 33 (0.8%) patients. Of these, 26 were
      male, mean age was 59 +/- 12 and APACHE-III score was 75 +/- 31. Reasons for
      transfer to the ICU were congestive heart failure in 64%, septic shock in 21%,
      neurological deterioration in 15% and cardiopulmonary resuscitation in 9%.
      Inotropes or vasoconstrictors were required in 73% and multiorgan failure
      developed in 64% of the patients. Prosthetic valve endocarditis was present in
      21%. Gram-positive cocci were found in 96% of all positive cultures; cultures
      were negative in 27% of the patients. Transthoracic echocardiograms were
      diagnostic in only 33% and transesophageal studies were required in 91% to
      confirm diagnosis or fully to delineate the extent of disease. Surgical
      intervention was performed in 60% of the patients, and the remaining 40% were
      only treated medically. The APACHE-III score on admission did not differ
      statistically between the two groups (69 +/- 30 versus 84 +/- 34, P = 0.17). In
      patient mortality was 84% in patients treated medically, and 35% in surgically
      treated patients. Using multivariate analysis, acute renal failure on admission
      was identified as the independent single predictor for in-patient death (OR 5,
      95% CI 1.04-24.03, P = 0.04). CONCLUSION: The prognosis for patients with
      infective endocarditis requiring admission to a medical ICU is serious.
      Nevertheless, the data suggest that surgical intervention may be successfully
      performed in a substantial number of patients despite the presence of severe
      shock and occurrence of multiorgan failure.

PMID- 11983042
TI  - Acetaminophen toxicity: suicidal vs. accidental.
AB  - INTRODUCTION: Acetaminophen toxicity, which can lead to hepatotoxicity, is a
      burden on our health care system and contributes significantly to intensive care
      unit admissions and cost of hospitalization. The aim of our study was to
      determine the epidemiology of various types of acetaminophen poisoning and
      analyze their outcome compared with their admission characteristics. METHODS: We
      identified 93 consecutive patients, hospitalized for acetaminophen toxicity over
      a 52-month period from 1996 to 1999 in our urban county hospital. Retrospective
      case-control analysis was carried out using the data obtained from the medical
      records. RESULTS: Acetaminophen accounted for 7.5% of all cases of poisoning
      admitted during this period. Of the 93 patients, 80 were classified as suicidal
      and 13 had accidentally poisoned themselves in an attempt to relieve pain. The
      ratio of females to males was found to be 2:1. Of the 93 patients studied, 88
      were admitted to the intensive care unit for initial 24-48 hours of monitoring.
      Peak acetaminophen levels were higher in the suicidal overdose group (mean 121.7
      +/- 97.0 mg/l vs. 64.5 +/- 61.8 mg/l, P < 0.05) than in the accidental group. In
      spite of this, peak aminotransferase levels >1000 IU/l were more often seen in
      the latter (39% vs. 12%, P < 0.05). Hepatic coma and death were seen more often
      in the accidental overdose group (15% vs 0%, P < 0.05). Interestingly chronic
      alcohol abuse was also more frequent in the accidental overdose category (39% vs
      18%, P = 0.05). DISCUSSION: Although the peak acetaminophen level in the suicidal
      group was significantly higher, cases of therapeutic misadventure had higher
      rates of morbidity and mortality. Peak acetaminophen levels correlate poorly with
      hepatic dysfunction, morbidity and mortality. CONCLUSION: We recommend that the
      patients with suicidal acetaminophen overdose, without any concomitant poisoning,
      can safely managed on the medical floors.

PMID- 11983043
TI  - Tidal breathing flow-volume loops in bronchiolitis in infancy: the effect of
      albuterol [ISRCTN47364493].
AB  - OBJECTIVES: To evaluate the effect of nebulized albuterol on tidal breathing flow
      volume loops in infants with bronchiolitis due to respiratory syncytial virus.
      DESIGN: A randomized, double-blind, control study. SETTING: Pediatric unit in a
      community teaching hospital. PARTICIPANTS: Twenty infants younger than 1 year of
      age (mean age, 5.8 +/- 2.8 months) with a first episode of wheezing due to
      respiratory syncytial virus bronchiolitis. INTERVENTIONS: Chloral hydrate (50
      mg/kg) was administered orally for sedation. One dose each of nebulized albuterol
      (0.15 mg/kg in 3 ml saline) and saline (3 ml) were given at 6 hour intervals in a
      random order. MEASUREMENTS: Tidal breathing flow-volume loops were obtained
      before and after each aerosol treatment with a Neonatal/Pediatric Pulmonary
      Testing System (Model 2600; Sensor Medics, Anaheim, CA, USA). At the same time,
      the fraction of tidal volume exhaled at peak tidal expiratory flow (PTEF) to
      total tidal volume (VPTEF/VE), and the fraction of exhaled time at PTEF to total
      expiratory time (tPTEF/tE) were measured. The PTEF, the tidal expiratory flows at
      10%, 25%, and 50% of the remaining tidal volume (TEF10, TEF25, and TEF50), and
      the wheeze score were also determined. RESULTS: There were no significant changes
      in VPTEF/VE and tPTEF/tE after albuterol or saline treatment. PTEF increased
      significantly both after albuterol and saline treatments but the difference
      between the two treatments was not significant (P = 0.6). Both TEF10 and the
      ratio of the tidal expiratory flow at 25% of the remaining tidal volume to PTEF
      (25/PT) decreased significantly (P < 0.05) after administration of albuterol. All
      other investigated variables were not significantly affected by aerosol
      administration. CONCLUSIONS: Nebulized albuterol in infants with mild
      bronchiolitis due to respiratory syncytial virus did not improve VPTEF/VE and
      tPTEF/tE but did decrease TEF10 and 25/PT.

PMID- 11983044
TI  - Assessment of performance of four mortality prediction systems in a Saudi Arabian
      intensive care unit.
AB  - INTRODUCTION: The purpose of this study is to assess the performance of Acute
      Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology
      Score (SAPS) II, Mortality Probability Model MPM II0 and MPM II24 systems in a
      major tertiary care hospital in Riyadh, Saudi Arabia. METHODS: The following data
      were collected prospectively on all consecutive patients admitted to the
      Intensive Care Unit between 1 March 1999 and 31 December 2000: demographics,
      APACHE II and SAPS II scores, MPM variables, ICU and hospital outcome. Predicted
      mortality was calculated using original regression formulas. Standardized
      mortality ratio (SMR) was computed with 95% confidence intervals (CI).
      Calibration was assessed by calculating Lemeshow-Hosmer goodness-of-fit C
      statistics. Discrimination was evaluated by calculating the Area Under the
      Receiver Operating Characteristic Curves (ROC AUC). RESULTS: Predicted mortality
      by all systems was not significantly different from actual mortality [SMR for MPM
      II0: 1.00 (0.91-1.10), APACHE II: 1.00 (0.8-1.11), SAPS II: 1.09 (0.97-1.21), MPM
      II24 0.92 (0.82-1.03)]. Calibration was best for MPM II24 (C-statistic: 14.71, P
      = 0.06). Discrimination was best for MPM II0 (ROC AUC:0.85) followed by MPM II24
      (0.84), APACHE II (0.83) then SAPS II (0.79). CONCLUSIONS: In our ICU population:
      1) Overall mortality prediction, estimated by standardized mortality ratio, was
      accurate, especially for MPM II0 and APACHE II. 2) MPM II24 has the best
      calibration. 3) SAPS II has the lowest calibration and discrimination. The local
      performance of MPM II24 in addition to its ease-to-use makes it an attractive
      model for mortality prediction in Saudi Arabia.

PMID- 11983045
TI  - Echocardiography: a fundamental part of the intensive care curriculum.

PMID- 11983048
TI  - What's in a name?

PMID- 11983049
TI  - Life sentences: Ontology recapitulates philology.

PMID- 11983050
TI  - Is 'big biology' a commercial enterprise?
AB  - Big projects in biology - such as the human genome project and a number of
      related and ensuing enterprises - require big funding. A new tradition is growing
      in which some types of basic research take place within commercial organizations.
      This article reviews some of the reasons for this and some of the key players, in
      the USA, Europe and Japan, and highlights some issues to be considered when
      deciding whether particular research belongs in a company rather than an academic
      setting.

PMID- 11983051
TI  - Protein structure and function by the sea.

PMID- 11983052
TI  - Cell-cycle regulation.

PMID- 11983053
TI  - Genome informatics for data-driven biology.

PMID- 11983054
TI  - Use of genomic data in risk assessment.

PMID- 11983055
TI  - Chips to hits.

PMID- 11983057
TI  - Evaluation and classification of RING-finger domains encoded by the Arabidopsis
      genome.
AB  - BACKGROUND: In computational analysis, the RING-finger domain is one of the most
      frequently detected domains in the Arabidopsis proteome. In fact, it is more
      abundant in Arabidopsis than in other eukaryotic genomes. However, computational
      analysis might classify ambiguous domains of the closely related PHD and LIM
      motifs as RING domains by mistake. Thus, we set out to define an ordered set of
      Arabidopsis RING domains by evaluating predicted domains on the basis of recent
      structural data. RESULTS: Inspection of the proteome with a current InterPro
      release predicts 446 RING domains. We evaluated each detected domain and as a
      result eliminated 59 false positives. The remaining 387 domains were grouped by
      cluster analysis and according to their metal-ligand arrangement. We further
      defined novel patterns for additional computational analyses of the proteome.
      They were based on recent structural data that enable discrimination between the
      related RING, PHD and LIM domains. These patterns allow us to predict with
      different degrees of certainty whether a particular domain is indeed likely to
      form a RING finger. CONCLUSIONS: In summary, 387 domains have a significant
      potential to form a RING-type cross-brace structure. Many of these RING domains
      overlap with predicted PHD domains; however, the RING domain signature mostly
      prevails. Thus, the abundance of PHD domains in Arabidopsis has been
      significantly overestimated. Cluster analysis of the RING domains defines groups
      of proteins, which frequently show significant similarity outside the RING
      domain. These groups document a common evolutionary origin of their members and
      potentially represent genes of overlapping functionality.

PMID- 11983056
TI  - Evolutionary conservation of otd/Otx2 transcription factor action: a genome-wide
      microarray analysis in Drosophila.
AB  - BACKGROUND: Homeobox genes of the orthodenticle (otd)/Otx family have conserved
      roles in the embryogenesis of head and brain. Gene replacement experiments show
      that the Drosophila otd gene and orthologous mammalian Otx genes are functionally
      equivalent, in that overexpression of either gene in null mutants of Drosophila
      or mouse can restore defects in cephalic and brain development. This suggests
      that otd and Otx genes control a comparable subset of downstream target genes in
      either organism. Here we use quantitative transcript imaging to analyze this
      equivalence of otd and Otx gene action at a genomic level. RESULTS:
      Oligonucleotide arrays representing 13,400 annotated Drosophila genes were used
      to study differential gene expression in flies in which either the Drosophila otd
      gene or the human Otx2 gene was overexpressed. Two hundred and eighty-seven
      identified transcripts showed highly significant changes in expression levels in
      response to otd overexpression, and 682 identified transcripts showed highly
      significant changes in expression levels in response to Otx2 overexpression.
      Among these, 93 showed differential expression changes following overexpression
      of either otd or Otx2, and for 90 of these, comparable changes were observed
      under both experimental conditions. We postulate that these transcripts are
      common downstream targets of the fly otd gene and the human Otx2 gene in
      Drosophila. CONCLUSION: Our experiments indicate that approximately one third of
      the otd-regulated transcripts also respond to overexpression of the human Otx2
      gene in Drosophila. These common otd/Otx2 downstream genes are likely to
      represent the molecular basis of the functional equivalence of otd and Otx2 gene
      action in Drosophila.

PMID- 11983058
TI  - New feature subset selection procedures for classification of expression
      profiles.
AB  - BACKGROUND: Methods for extracting useful information from the datasets produced
      by microarray experiments are at present of much interest. Here we present new
      methods for finding gene sets that are well suited for distinguishing experiment
      classes, such as healthy versus diseased tissues. Our methods are based on
      evaluating genes in pairs and evaluating how well a pair in combination
      distinguishes two experiment classes. We tested the ability of our pair-based
      methods to select gene sets that generalize the differences between experiment
      classes and compared the performance relative to two standard methods. To assess
      the ability to generalize class differences, we studied how well the gene sets we
      select are suited for learning a classifier. RESULTS: We show that the gene sets
      selected by our methods outperform the standard methods, in some cases by a large
      margin, in terms of cross-validation prediction accuracy of the learned
      classifier. We show that on two public datasets, accurate diagnoses can be made
      using only 15-30 genes. Our results have implications for how to select marker
      genes and how many gene measurements are needed for diagnostic purposes.
      CONCLUSION: When looking for differential expression between experiment classes,
      it may not be sufficient to look at each gene in a separate universe. Evaluating
      combinations of genes reveals interesting information that will not be discovered
      otherwise. Our results show that class prediction can be improved by taking
      advantage of this extra information.

PMID- 11983059
TI  - Empirical characterization of the expression ratio noise structure in high
      density oligonucleotide arrays.
AB  - BACKGROUND: High-density oligonucleotide arrays (HDONAs) are a powerful tool for
      assessing differential mRNA expression levels. To establish the statistical
      significance of an observed change in expression, one must take into account the
      noise introduced by the enzymatic and hybridization steps, called type I noise.
      We undertake an empirical characterization of the experimental repeatability of
      results by carrying out statistical analysis of a large number of duplicate HDONA
      experiments. RESULTS: We assign scoring functions for expression ratios and
      associated quality measures. Both the perfect-match (PM) probes and the
      differentials between PM and single-mismatch (MM) probes are considered as raw
      intensities. We then calculate the log-ratio of the noise structure using robust
      estimates of their intensity-dependent variance. The noise structure in the log
      ratios follows a local log-normal distribution in both the PM and PM-MM cases.
      Significance relative to the type I noise can therefore be quantified reliably
      using the local standard deviation (SD). We discuss the intensity dependence of
      the SD and show that ratio scores greater than 1.25 are significant in the mid-
      to high-intensity range. CONCLUSIONS: The noise inherent in HDONAs is
      characteristically dependent on intensity and can be well described in terms of
      local normalization of log-ratio distributions. Therefore, robust estimates of
      the local SD of these distributions provide a simple and powerful way to assess
      significance (relative to type I noise) in differential gene expression, and will
      be helpful in practice for improving the reliability of predictions from
      hybridization experiments.

PMID- 11983060
TI  - Permutation-validated principal components analysis of microarray data.
AB  - BACKGROUND: In microarray data analysis, the comparison of gene-expression
      profiles with respect to different conditions and the selection of biologically
      interesting genes are crucial tasks. Multivariate statistical methods have been
      applied to analyze these large datasets. Less work has been published concerning
      the assessment of the reliability of gene-selection procedures. Here we describe
      a method to assess reliability in multivariate microarray data analysis using
      permutation-validated principal components analysis (PCA). The approach is
      designed for microarray data with a group structure. RESULTS: We used PCA to
      detect the major sources of variance underlying the hybridization conditions
      followed by gene selection based on PCA-derived and permutation-based test
      statistics. We validated our method by applying it to well characterized yeast
      cell-cycle data and to two datasets from our laboratory. We could describe the
      major sources of variance, select informative genes and visualize the
      relationship of genes and arrays. We observed differences in the level of the
      explained variance and the interpretability of the selected genes. CONCLUSIONS:
      Combining data visualization and permutation-based gene selection, permutation
      validated PCA enables one to illustrate gene-expression variance between several
      conditions and to select genes by taking into account the relationship of between
      group to within-group variance of genes. The method can be used to extract the
      leading sources of variance from microarray data, to visualize relationships
      between genes and hybridizations and to select informative genes in a
      statistically reliable manner. This selection accounts for the level of
      reproducibility of replicates or group structure as well as gene-specific
      scatter. Visualization of the data can support a straightforward biological
      interpretation.

PMID- 11983061
TI  - Organellar proteomics: the prizes and pitfalls of opening the nuclear envelope.
AB  - Proteomic studies have the potential to comprehensively define the composition of
      organelles but are limited by the organellar cross-contamination that arises
      during subcellular fractionation. Comparative proteomics of organellar
      subfractions can mitigate these problems, as demonstrated by a recent study
      involving the nuclear envelope.

PMID- 11983062
TI  - Screening the yeast genome for new DNA-repair genes.
AB  - Studies of DNA repair and the maintenance of genomic integrity are essential to
      understanding the etiology and pathology of cancer. The availability of the
      complete genome sequence of Saccharomyces cerevissiae has greatly facilitated the
      discovery of new genes important for DNA repair.

PMID- 11983063
TI  - Screening the fruitfly immune system.
AB  - The anti-microbial defense system of Drosophila shows functional similarities
      with the vertebrate innate immune system. Two recent gene-expression profiling
      studies of fruitflies challenged with infectious agents have identified key
      molecular players in the fruitfly's response to bacterial and fungal infection,
      as well as a large number of immune-regulated genes with unknown immunological
      function.

PMID- 11983064
TI  - Genome scans and microarrays: converging on genes for schizophrenia?
AB  - Systematic genome-wide scans to date have shown that genes of major effect are
      not common causes of schizophrenia, but independent linkage studies looking for
      schizophrenia susceptibility genes are converging on a number of key chromosomal
      locations. Microarray expression analysis may identify new candidate genes and
      pathways, and a number of intriguing preliminary findings have already been
      reported.

PMID- 11983065
TI  - ATP-dependent DNA ligases.
AB  - SUMMARY: By catalyzing the joining of breaks in the phosphodiester backbone of
      duplex DNA, DNA ligases play a vital role in the diverse processes of DNA
      replication, recombination and repair. Three related classes of ATP-dependent DNA
      ligase are readily apparent in eukaryotic cells. Enzymes of each class comprise
      catalytic and non-catalytic domains together with additional domains of varying
      function. DNA ligase I is required for the ligation of Okazaki fragments during
      lagging-strand DNA synthesis, as well as for several DNA-repair pathways; these
      functions are mediated, at least in part, by interactions between DNA ligase I
      and the sliding-clamp protein PCNA. DNA ligase III, which is unique to
      vertebrates, functions both in the nucleus and in mitochondria. Two distinct
      isoforms of this enzyme, differing in their carboxy-terminal sequences, are
      produced by alternative splicing: DNA ligase IIIalpha has a carboxy-terminal BRCT
      domain that interacts with the mammalian DNA-repair factor XrccI, but both alpha
      and beta isoforms have an amino-terminal zinc-finger motif that appears to play a
      role in the recognition of DNA secondary structures that resemble intermediates
      in DNA metabolism. DNA ligase IV is required for DNA non-homologous end joining
      pathways, including recombination of the V(D)J immunoglobulin gene segments in
      cells of the mammalian immune system. DNA ligase IV forms a tight complex with
      Xrcc4 through an interaction motif located between a pair of carboxy-terminal
      BRCT domains in the ligase. Recent structural studies have shed light on the
      catalytic function of DNA ligases, as well as illuminating protein-protein
      interactions involving DNA ligases IIIalpha and IV.

PMID- 11983066
TI  - Retroviral proteases.
AB  - SUMMARY: The proteases of retroviruses, such as leukemia viruses,
      immunodeficiency viruses (including the human immunodeficiency virus, HIV),
      infectious anemia viruses, and mammary tumor viruses, form a family with the
      proteases encoded by several retrotransposons in Drosophila and yeast and
      endogenous viral sequences in primates. Retroviral proteases are key enzymes in
      viral propagation and are initially synthesized with other viral proteins as
      polyprotein precursors that are subsequently cleaved by the viral protease
      activity at specific sites to produce mature, functional units. Active retroviral
      proteases are homodimers, with each dimer structurally related to the larger
      class of single-chain aspartic peptidases. Each monomer has four structural
      elements: two distinct hairpin loops, a wide loop containing the catalytic
      aspartic acid and an alpha helix. Retroviral gene sequences can vary between
      infected individuals, and mutations affecting the binding cleft of the protease
      or the substrate cleavage sites can alter the response of the virus to
      therapeutic drugs. The need to develop new drugs against HIV will continue to be,
      to a large extent, the driving force behind further characterization of
      retroviral proteases.

PMID- 11983067
TI  - Diacylglycerol kinases: emerging downstream regulators in cell signaling systems.
AB  - Diacylglycerol kinase (DGK) regulates signal transduction by modulating the
      balance between the two signaling lipids, diacylglycerol and phosphatidic acid.
      DGK and its homologs occur in a wide range of multicellular organisms and the
      mammalian DGK is known to consist of nine members with a considerable incidence
      of alternative splicing. Recent work has established that DGK serves as a key
      attenuator of diacylglycerol of signaling functions and that the mammalian
      isozymes are equipped with molecular machineries which enable them to act in
      specific intracellular sites and/or in signaling protein complexes.

PMID- 11983068
TI  - Platelet-activating factor acetylhydrolase (PAF-AH).
AB  - Platelet-activating factor (PAF) is one of the most potent lipid messengers
      involved in a variety of physiological events. The acetyl group at the sn-2
      position of its glycerol backbone is essential for its biological activity, and
      its deacetylation induces loss of activity. The deacetylation reaction is
      catalyzed by PAF-acetylhydrolase (PAF-AH). A series of biochemical and
      enzymological evaluations revealed that at least three types of PAF-AH exist in
      mammals, namely the intracellular types I and II and a plasma type. Type I PAF-AH
      is a G-protein-like complex consisting of two catalytic subunits (alpha1 and
      alpha2) and a regulatory beta subunit. The beta subunit is a product of the LIS1
      gene, mutations of which cause type I lissencephaly. Recent studies indicate that
      LIS1/beta is important in cellular functions such as induction of nuclear
      movement and control of microtubule organization. Although substantial evidence
      is accumulating supporting the idea that the catalytic subunits are also involved
      in microtubule function, it is still unknown what role PAF plays in the process
      and whether PAF is an endogenous substrate of this enzyme. Type II PAF-AH is a
      single polypeptide and shows significant sequence homology with plasma PAF-AH.
      Type II PAF-AH is myristoylated at the N-terminus and like other N-myristoylated
      proteins is distributed in both the cytosol and membranes. Plasma PAF-AH is also
      a single polypeptide and exists in association with plasma lipoproteins. Type II
      PAF-AH as well as plasma PAF-AH may play a role as a scavenger of oxidized
      phospholipids which are thought to be involved in diverse pathological processes,
      including disorganization of membrane structure and PAF-like proinflammatory
      action. In this review, we will focus on the structures and possible biological
      functions of intracellular PAF-AHs.

PMID- 11983069
TI  - Essential light chain modulates phosphorylation-dependent regulation of smooth
      muscle myosin.
AB  - To examine the functional role of the essential light chain (ELC) in the
      phosphorylation-dependent regulation of smooth muscle myosin, we replace the
      native light chain in smooth muscle myosin with bacterially expressed chimeric
      ELCs in which one or two of the four helix-loop-helix domains of chicken gizzard
      ELC were substituted by the corresponding domains of scallop (Aquipecten
      irradians) ELC. All of these myosins, regardless of the ELC mutations or
      regulatory light chain (RLC) phosphorylation, showed normal subunit constitutions
      and NH(4)(+)/EDTA-ATPase activities, both of which were similar to those of
      native myosin. None of the ELC mutations changed the actin-activated ATPase
      activity of myosin in the absence of RLC phosphorylation. However, in the
      presence of RLC phosphorylation, the substitution of domain 1 or 2 in the ELC
      significantly decreased the actin-activated ATPase activity, whereas the
      substitution of both of these domains did not change the activity. In contrast to
      myosin, the domain 2 substitution in the ELC did not affect the actin-activated
      ATPase activity of single-headed myosin subfragment 1. These results suggest an
      interhead interaction between domains 1 and 2 of ELCs which is required to attain
      the full actin-activated ATPase activity of smooth muscle myosin in the presence
      of RLC phosphorylation.

PMID- 11983070
TI  - The first molecular evidence that autophagy relates rimmed vacuole formation in
      chloroquine myopathy.
AB  - Chloroquine myopathy is a drug poisoning disease involving rimmed vacuole
      formation. By Western blot analysis, we investigated posttranslational
      modification of LC3 in cultured cells with a high concentration of chloroquine,
      and found that the autophagosome membrane-bound form of LC3 increased dose
      dependently. We also constructed a disease model by excessive chloroquine
      injection into rats and unusual immunohistochemical alteration was chased using
      anti-LC3 antibodies. With chloroquine treatment, muscle atrophy occurred
      predominantly in soleus muscle and unusual autophagosomes were accumulated.
      Therefore, we concluded that autophagy plays an important role in rimmed vacuole
      formation in certain muscular atrophies.

PMID- 11983071
TI  - FosB gene products trigger cell proliferation and morphological alteration with
      an increased expression of a novel processed form of galectin-1 in the rat 3Y1
      embryo cell line.
AB  - In this study, we established rat 3Y1 embryo cell lines expressing FosB and
      DeltaFosB as fusion proteins (ER-FosB, ER-DeltaFosB) with the ligand-binding
      domain of human estrogen receptor (ER). The binding of estrogen to the fusion
      proteins resulted in their nuclear translocation. After estrogen administration,
      exponentially growing cells expressing ER-DeltaFosB, and to a lesser extent ER
      FosB, underwent morphological alteration from the flat fibroblastic shape to an
      extended bipolar shape, and ceased proliferating. Such morphological alteration
      was also induced in quiescent cells expressing ER-DeltaFosB and ER-FosB after one
      round of cell division triggered by estrogen administration. The cells expressing
      ER-DeltaFosB changed shape frequently, and the content of F-actin in the
      cytoplasm detected by binding of Alexa 488-phalloidin significantly decreased
      after the morphological alteration. By two-dimensional gel electrophoresis
      analysis of cellular proteins from the cells expressing ER-DeltaFosB, we
      identified several proteins whose expression either increased or decreased after
      estrogen administration. Two of these proteins were identified from their amino
      acid sequences as novel processed form of galectin-1.

PMID- 11983072
TI  - Amino acid residues in subsites e and f responsible for the characteristic
      enzymatic activity of duck egg-white lysozyme.
AB  - We analyzed the enzymatic properties of duck egg-white lysozyme II (DEL), which
      differs from hen egg-white lysozyme (HEL) in nineteen amino acid substitutions. A
      substrate binding study showed that DEL binds to the substrate analog at subsites
      A-C in the same manner as HEL. However, the experimental time-courses of DEL
      against the substrate N-acetylglucosamine pentamer, (GlcNAc)(5), revealed
      remarkably enhanced production of (GlcNAc)(2) and reduced production of
      (GlcNAc)(1) as compared to in the case of HEL. Computer simulation of the DEL
      catalyzed reaction suggested that the amino acid substitutions at subsites E and
      F (Phe34 to Tyr and Asn37 to Ser) caused the great alteration in the time-courses
      of DEL. Subsequently, the enzymatic reactions of mutants, in which Phe34 and
      Asn37 in HEL were converted to Tyr and Ser, respectively, were characterized. The
      time-courses of the F34Y mutant exhibited profiles similar to those of HEL. In
      contrast, the characteristics of the N37S mutant were different from those of HEL
      and rather similar to those of DEL; the order of the amounts of (GlcNAc)(1) and
      (GlcNAc)(2) was reversed in comparison with in the case of HEL. Enhanced
      production of (GlcNAc)(2) was also observed for the mutant protein, F34Y/N37S,
      with two substitutions. These results indicated that the substitution of Asn37
      with Ser can account, at least in part, for the characteristic time-courses of
      DEL. Moreover, replacement of Asn37 with Ser reduced the rate constant of
      transglycosylation. The substitution of the Asn37 residue may affect the
      transglycosylation activity of HEL.

PMID- 11983073
TI  - Catalysis-linked inactivation of fluoroacetate dehalogenase by ammonia: a novel
      approach to probe the active-site environment.
AB  - Fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX) catalyzes the
      hydrolytic dehalogenation of fluoroacetate and other haloacetates. Asp(105) of
      the enzyme acts as a nucleophile to attack the alpha-carbon of haloacetate to
      form an ester intermediate, which is subsequently hydrolyzed by a water molecule
      activated by His(272) [Liu, J.Q., Kurihara, T., Ichiyama, S., Miyagi, M.,
      Tsunasawa, S., Kawasaki, H., Soda, K., and Esaki, N. (1998) J. Biol. Chem. 273,
      30897-30902]. In this study, we found that FAc-DEX is inactivated concomitantly
      with defluorination of fluoroacetate by incubation with ammonia. Mass
      spectrometric analyses revealed that the inactivation of FAc-DEX is caused by
      nucleophilic attack of ammonia on the ester intermediate to convert the catalytic
      residue, Asp(105), into an asparagine residue. The results indicate that ammonia
      reaches the active site of FAc-DEX without losing its nucleophilicity. Analysis
      of the three-dimensional structure of the enzyme by homology modeling showed that
      the active site of the enzyme is mainly composed of hydrophobic and basic
      residues, which are considered to be essential for an ammonia molecule to retain
      its nucleophilicity. In a normal enzyme reaction, the hydrophobic environment is
      supposed to prevent hydration of the highly electronegative fluorine atom of the
      substrate and contribute to fluorine recognition by the enzyme. Basic residues
      probably play a role in counterbalancing the electronegativity of the substrate.
      These results demonstrate that catalysis-linked inactivation is useful for
      characterizing the active-site environment as well as for identifying the
      catalytic residue.

PMID- 11983074
TI  - Structure of external aldimine of Escherichia coli CsdB, an IscS/NifS homolog:
      implications for its specificity toward selenocysteine.
AB  - Escherichia coli CsdB is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that
      catalyzes both cysteine desulfuration and selenocysteine deselenation. The enzyme
      has a high specific activity for L-selenocysteine relative to L-cysteine. On the
      other hand, its paralog, IscS, exhibits higher activity for L-cysteine, which
      acts as a sulfur donor during the biosynthesis of the iron-sulfur cluster and 4
      thiouridine. The structure of CsdB complexed with L-propargylglycine was
      determined by X-ray crystallography at 2.8 A resolution. The overall polypeptide
      fold of the complex is similar to that of the uncomplexed enzyme, indicating that
      no significant structural change occurs upon formation of the complex. In the
      complex, propargylglycine forms a Schiff base with PLP, providing the features of
      the external aldimine formed in the active site. The Cys364 residue, which is
      essential for the activity of CsdB toward L-cysteine but not toward L
      selenocysteine, is clearly visible on a loop of the extended lobe (Thr362-Arg375)
      in all enzyme forms studied, in contrast to the corresponding disordered loop
      (Ser321-Arg332) of the Thermotoga maritima NifS-like protein, which is closely
      related to IscS. The extended lobe of CsdB has an 11-residue deletion compared
      with that of the NifS-like protein. These facts suggest that the restricted
      flexibility of the Cys364-anchoring extended lobe in CsdB may be responsible for
      the ability of the enzyme to discriminate between selenium and sulfur.

PMID- 11983075
TI  - Enhancement in the cleavage activity of a hammerhead ribozyme by cationic comb
      type polymers and an RNA helicase in vitro.
AB  - The activity of a hammerhead ribozyme (Rz) in vivo depends on several factors,
      such as abundance, stability, and accessibility of Rz to its target mRNA. Among
      these factors, accessibility is believed to be the rate-limiting factor for Rz
      mediated cleavage in vivo. As Rz and its substrate RNA are negatively charged, we
      examined whether cellular RNA-interacting proteins or artificial polycations
      might improve the accessibility of Rz to its substrate RNA. Specifically, we
      examined the effects of two kinds of cationic comb-type copolymer, alphaPLL-g
      Dex, and a cellular RNA helicase on the accessibility of Rz to a model structured
      RNA in vitro. The cleavage activity of Rz was slightly enhanced by alphaPLL-g
      Dex, probably due to an acceleration of the association/dissociation rate. And
      also, the RNA helicase-bound hybrid-Rz could cleave the target substrate at a
      significantly higher rate due to its unwinding activity for the duplex RNA
      substrate. These approaches should be useful in the development of efficient gene
      inactivating reagents in the post-genomic era.

PMID- 11983076
TI  - Phosphoinositide 3-OH kinase/protein kinase B inhibits apoptotic cell death
      induced by reactive oxygen species in Saccharomyces cerevisiae.
AB  - Apoptosis is a common mode of programmed cell death in multicellular organisms.
      However, the recent observation of yeast cell death displaying the morphology of
      apoptosis has suggested the presence of an ancestral cell death machinery. Here
      we examined apoptotic features induced by reactive oxygen species (ROS) in yeast.
      Saccharomyces cerevisiae show typical apoptotic features upon exposure to ROS:
      membrane staining with annexin V and DNA fragmentation by the TUNEL assay. The
      detection of apoptotic features in yeast strongly support the existence of
      molecular machinery performing the basic pathways of apoptosis. The
      phosphoinositide 3-OH kinase (PI3K)/protein kinase B (PKB) signaling pathway has
      been shown to prevent apoptosis in a variety of cells. It is therefore of
      interest to determine whether the PI3K/PKB signaling pathway is capable of
      protecting yeast from apoptosis induced by ROS. We determined that PI3K/PKB is
      capable of significantly inhibiting ROS-evoked apoptosis in yeast. These results
      suggest that yeast may provide a suitable model system in which to study the
      apoptotic signaling pathway elicited by a variety of stimuli.

PMID- 11983077
TI  - Fluctuations in free or substrate-complexed lysozyme and a mutant of it detected
      on x-ray crystallography and comparison with those detected on NMR.
AB  - A mutant lysozyme in which Arg14 and His15 were deleted together exhibited higher
      activity toward glycol chitin than the wild-type lysozyme. Moreover, the mutant
      lysozyme, which is less stable than the wild-type lysozyme by 7 degrees C, showed
      a shift of temperature dependence of activity to the low temperature side
      compared with the wild-type lysozyme [Protein Eng. 7, 743-748 (1994)]. In the
      free enzyme, the internal motion of the mutant lysozyme was similar to that of
      the wild-type. The internal motions of the wild-type and mutant lysozymes in the
      enzyme-substrate complex increased more than those in the free enzymes. Moreover,
      the increased internal motions of the substrate-complexed mutant lysozyme were
      greater than those of the substrate-complexed wild-type lysozyme in several
      residues [J. Mol. Biol. 286, 1547-1565 (1999)]. The structure of the mutant
      lysozyme was very similar to that of the wild-type lysozyme. Both structures were
      also alike in the complex of the trimer of N-acetyl-D-glucosamine. The mobility
      from B-factors agreed to some degree with that from order parameters in the
      regions showing great mobility of the protein, but this was not the case in the
      regions showing fast motion. However, we came to the same conclusion that the
      increased activity of the mutant lysozyme is due to the increase in the
      fluctuation of the lysozyme molecule. B-factor and order parameter do not always
      exhibit harmony because the time-scale of the analysis of mobility is different.
      However, they are not incompatible but complementary for detecting precise
      protein motions.

PMID- 11983078
TI  - Heterologous expression and catalytic properties of the C-terminal domain of
      starfish cdc25 dual-specificity phosphatase, a cell cycle regulator.
AB  - The 3'-terminal region of starfish Asterina pectinifera cdc25 cDNA encoding the C
      terminal catalytic domain was overexpressed in Escherichia coli. The C-terminal
      domain consisted of 226 amino acid residues containing the signature motif
      HCxxxxxR, a motif highly conserved among protein tyrosine and dual-specificity
      phosphatases, and showed phosphatase activity toward p-nitrophenyl phosphate. The
      enzyme activity was strongly inhibited by SH inhibitors. Mutational studies
      indicated that the cysteine and arginine residues in the conserved motif are
      essential for activity, but the histidine residue is not. These results suggest
      that the enzyme catalyzes the reaction through a two-step mechanism involving a
      phosphocysteine intermediate like in the cases of other protein tyrosine and dual
      specificity phosphatases. The C-terminal domain of Cdc25 activated the histone H1
      kinase activity of the purified, inactive form of Cdc2.cyclin B complex (preMPF)
      from extracts of immature starfish oocytes. Synthetic diphosphorylated di- to
      nonadecapeptides mimicking amino acid sequences around the dephosphorylation site
      of Cdc2 still retained substrate activity. Phosphotyrosine and phosphothreonine
      underwent dephosphorylation in this order. This is the reverse order to that
      reported for the in vivo and in vitro dephosphorylation of preMPF.
      Monophosphopeptides having the same sequence served as much poorer substrates. As
      judged from the results with synthetic phosphopeptides, the presence of two
      phosphorylated residues was important for specific recognition of substrates by
      the Cdc25 phosphatase.

PMID- 11983079
TI  - Network of protein-protein interactions among iron-sulfur cluster assembly
      proteins in Escherichia coli.
AB  - The assembly of iron-sulfur (Fe-S) clusters is mediated by complex machinery
      which, in Escherichia coli, is encoded by the iscRSUA-hscBA-fdx-ORF3 gene
      cluster. Here, we demonstrate the network of protein-protein interactions among
      the components involved in the machinery. We have constructed (His)(6)-tagged
      versions of the components and identified their interacting partners that were co
      purified from E. coli extracts with a Ni-affinity column. Direct associations of
      the defined pair of proteins were further examined in yeast cells using the two
      hybrid system. In accord with the previous in vitro binding and kinetic
      experiments, interactions were observed for the combinations of IscS and IscU,
      IscU and HscB, IscU and HscA, and HscB and HscA. In addition, we have identified
      previously unreported interactions between IscS and Fdx, IscS and ORF3, IscA and
      HscA, and HscA and Fdx. We also found, by site-directed mutational analysis
      combined with the two-hybrid system, that two cysteine residues in IscU are
      essential for binding with HscB but not with IscS. Despite the complex network of
      interactions in various combinations of components, heteromultimeric complexes
      were not observed in our experiments except for the putative oligomeric form of
      IscU-IscS-ORF3. Thus, the sequential association and dissociation among the IscS,
      IscU, IscA, HscB, HscA, Fdx, and ORF3 proteins may be a critical process in the
      assembly of Fe-S clusters.

PMID- 11983080
TI  - Opening of mitochondrial ATP-sensitive potassium channels evokes oxygen radical
      generation in rabbit heart slices.
AB  - The purpose of this study was to determine whether ATP-sensitive potassium
      channel (K(ATP) channel) activation generates oxygen free radicals in the rabbit
      heart. We assayed malondialdehyde (MDA) in rabbit heart slices in vitro as an
      indicator of oxygen free radical generation. The K(ATP) channel openers,
      pinacidil and cromakalim, significantly increased MDA production in a
      concentration-dependent manner. MDA formation also increased linearly with
      incubation time in the presence of K(ATP) channel openers. The K(ATP) channel
      blockers, glibenclamide and 5-hydroxydecanoate (5-HD), decreased K(ATP) channel
      opener-induced MDA formation in a concentration-dependent manner. When Fe(2+) was
      administered to heart slices that had been pretreated with K(ATP) channel
      openers, a marked elevation in MDA was observed, compared to heart slices that
      were treated with Fe(2+) alone. A positive linear correlation between Fe(2+) and
      MDA level was observed. The MDA levels of heart slices subjected to anoxia for 15
      min remained unchanged until reperfusion. When the heart slices were reoxygenated
      for 30 min, a marked increase in MDA formation was observed. However, in the
      presence of glibenclamide and 5-HD, reperfusion following anoxia did not result
      in increased MDA. These results suggest that the opening of mitochondrial K(ATP)
      channels in rabbit heart slices evokes oxygen free radical generation via a
      Fenton-type reaction.

PMID- 11983081
TI  - Design, production, and characterization of recombinant neocarzinostatin
      apoprotein in Escherichia coli.
AB  - Neocarzinostatin (NCS) is the first discovered anti-tumor antibiotic having an
      enediyne-containing chromophore and an apoprotein with a 1:1 complex. An
      artificial gene library for NCS apoprotein (apo-NCS) production in Escherichia
      coli was designed and constructed on a phage-display vector, pJuFo. The
      recombinant phages expressing pre-apo-NCS protein were enriched with a mouse anti
      apo-NCS monoclonal antibody, 1C7D4. The apo-NCS gene (encsA) for E. coli was
      successfully cloned, and then re-cloned into the pRSET A vector. After the his
      tagged apo-NCS protein had been purified and cleaved with enterokinase, the
      binding properties of the recombinant protein as to ethidium bromide (EtBr) were
      studied by monitoring of total fluorescence intensity and fluorescence
      polarization with a BEACON 2000 system and GraphPad Prism software. A
      dissociation constant of 4.4 +/- 0.3 microM was obtained for recombinant apo-NCS
      in the fluorescence polarization study. This suggests that fluorescence
      polarization monitoring with EtBr as a chromophore mimic may be a simplified
      method for the characterization of recombinant apo-NCS binding to the NCS
      chromophore. When Phe78 on apo-NCS was substituted with Trp78 by site-directed
      mutagenesis using a two stage megaprimer polymerase chain reaction, the
      association of the apo-NCS mutant and EtBr observed on fluorescence polarization
      analysis was of the same degree as in the case of the wild type, although the
      calculated maximum change (DeltaIT(max)) in total fluorescence intensity
      decreased from 113.9 to 31.3. It was suggested that an environmental change of
      the bound EtBr molecule on F78W might have dramatically occurred as compared with
      in the case of wild type apo-NCS. This combination of monitoring of fluorescence
      polarization and total fluorescence intensity will be applicable for
      determination and prediction of the ligand state bound or associated with the
      target protein. The histone-specific proteolytic activity was also re
      investigated using this recombinant apo-NCS preparation, and calf thymus histone
      H1, H2A, H2B, H3, and H4. The recombinant apo-NCS does not act as a histone
      protease because a noticeable difference was not observed between the incubation
      mixtures with and without apo-NCS under our experimental conditions.

PMID- 11983082
TI  - Periodic binding of troponin C.I and troponin I to tropomyosin-actin filaments.
AB  - We investigated the distribution of troponin C.I and troponin I along tropomyosin
      actin filaments by immunoelectron microscopy and found that anti-troponin I
      antibody formed transverse striations at 38 nm intervals along the bundle of
      filaments of both troponin C.I-tropomyosin-actin and troponin I-tropomyosin
      actin. Since the length of 38 nm corresponds to the repeating period of
      filamentous tropomyosin along actin double strands, the present study indicates
      that troponin I is located at a specific region of each tropomyosin, suggesting
      that a specific interaction between troponin I and tropomyosin is involved in
      determining the periodic distribution of troponin I along tropomyosin-actin
      filaments.

PMID- 11983083
TI  - Regulation of complement-mediated swine endothelial cell lysis by herpes simplex
      virus glycoprotein, gC1.
AB  - Herpes simplex virus type 1 (HSV-1) encodes several immuno-regulatory proteins
      that allow it to escape from the human immune system. The regulatory function of
      a HSV-1 glycoprotein gC (HSV-gC1) molecule on complement-mediated swine
      endothelial cell (SEC) lysis was investigated. The HSV-gC1 gene was obtained by
      the PCR method from the HSV-1 genome. The complement-regulatory function of this
      molecule was analyzed by cytotoxicity assay, using Chinese hamster ovarian tumor
      (CHO) cell and SEC transfectants and six human serum samples. FACS and Western
      blot analysis revealed the expression of the HSV-gC1 molecule on the
      transfectants. The CHO cell transfectants showed significant resistance to cell
      lysis by the sera that did not contain the anti-HSV-gC1 antibody. The SEC
      transfectants, however, showed a marked resistance to cell lysis in all cases.
      The introduction of a viral immune regulator such as HSV-gC1 into the swine cell
      provides a new approach for successful xenotransplantation.

PMID- 11983084
TI  - Oligomerization process of the hemolytic lectin CEL-III purified from a sea
      cucumber, Cucumaria echinata.
AB  - CEL-III is a Ca(2+)-dependent lectin purified from a sea cucumber, Cucumaria
      echinata. This protein exhibits strong hemolytic activity as well as cytotoxicity
      toward some cultured cell lines. Hemolysis is caused by CEL-III oligomers formed
      in the cell membrane after binding to specific carbohydrate chains on the cell
      surface. We have found that the oligomerization of CEL-III is also induced by the
      binding of simple carbohydrates, such as lactose, in aqueous solution under high
      pH and high ionic strength conditions. From gel filtration analysis of the
      oligomerization of CEL-III, it was found that the formation of the CEL-III
      oligomer is effectively induced by the binding of lactose and lactulose,
      disaccharides containing a beta-galactoside structure. Electron micrographs of
      the resulting oligomers revealed them to exist as particles with a size of
      approximately 20-30 nm. The oligomerization process required more than 1 h, which
      is consistent with the increase in surface hydrophobicity as measured using a
      fluorescent probe, 8-anilinonaphthalene-1-sulfonate. However, a change in the far
      UV CD spectra as well as small-angle X-ray scattering occurred within a few
      minutes, suggesting that a structural change in the protein takes place rapidly,
      but the following growth of the oligomer is a much slower process.

PMID- 11983085
TI  - A CLN2-related and thermostable serine-carboxyl proteinase, kumamolysin: cloning,
      expression, and identification of catalytic serine residue.
AB  - The gene encoding kumamolysin, a thermostable pepstatin-insensitive carboxyl
      proteinase, was cloned and expressed. (i) Kumamolysin was synthesized as a large
      precursor consisting of two regions: amino-terminal prepro (188 amino acids) and
      mature proteins (384 amino acids). (ii) The deduced amino acid sequence of the
      mature region exhibited high similarity to those of such bacterial pepstatin
      insensitive enzymes as Pseudomonas carboxyl proteinase (PSCP; EC 3.4.23.37,
      identity = 37%), Xanthomonas carboxyl proteinase (XCP; EC 3.4.23.33, identity =
      36%), and human CLN2 gene product (identity = 36%), which is related to a fatal
      neurodegenerative disease. (iii) The presumed catalytic triad, Glu78, Asp82,
      Ser278 [three-dimensional structure of PSCP: Wlodawer, A. et al. (2001) Nature
      Struct. Biol., 8, 442-446], was found to be conserved in the amino acid sequence
      of kumamolysin. (iv) Kumamolysin was inactivated by such aldehyde-type inhibitors
      as Ac-Ile-Pro-Phe-CHO (K(i) = 0.7 0.14 microM). In PSCP, it has been clarified
      that these inhibitors form a hemiacetal linkage with the catalytic serine residue
      and inactivate the enzyme. (v) Mutational analysis of the Ser278 residue revealed
      that the mutant lost both auto-processing activity and proteolytic activity.
      These results strongly suggest that kumamolysin has a unique catalytic triad
      consisting of Glu78, Asp82, and Ser278 residues, as previously observed for PSCP.

PMID- 11983086
TI  - On the ethics of therapeutic cloning.

PMID- 11983087
TI  - Stem cells: moving ahead on all fronts.

PMID- 11983088
TI  - EpiStem, Ltd. [interview by Vicki P. Glaser].

PMID- 11983089
TI  - STI-stop transplanting immediately?

PMID- 11983090
TI  - Detection of an occult B-cell lymphoma in the donor's bone marrow prior to HLA
      matched sibling transplantation.

PMID- 11983091
TI  - Endothelial progenitor cells for vascular regeneration.
AB  - The basis for native as well as therapeutic neovascularization is not restricted
      to angiogenesis but includes postnatal vasculogenesis. Our laboratory and others'
      have established that bone marrow-derived endothelial progenitor cells (EPCs) are
      present in the systemic circulation, are augmented in response to certain
      cytokines and/or tissue ischemia, and home to as well as incorporate into sites
      of neovascularization. Given the background, EPCs have been investigated as
      therapeutic agents in these studies of supply-side angiogenesis under
      pathological as well as physiological conditions. This review discusses the
      therapeutic potential of EPCs for cardiovascular ischemic diseases.

PMID- 11983092
TI  - Role of monocytes and macrophages in adult angiogenesis: a light at the tunnel's
      end.
AB  - In spite of sustained efforts, there are still gaps in our understanding of
      angiogenesis as it takes place in vivo. Older observations and a number of recent
      developments strongly involve the blood mononuclear cell population, collectively
      known as monocytes (MC), in the normal and pathological adult angiogenesis. An
      emerging paradigm should eventually incorporate the established biochemical cross
      talk between MC and their descendents, tissular macrophages (Mph), and the
      endothelial cells (EC); additionally, it should account for both the
      intercellular cooperation at the morphological level and the phenotypic overlap
      between the two cell populations. This focused review puts together the pieces of
      this puzzle in such a way as to suggest an alternative angiogenic model
      applicable to adult animals, and particularly to pathological conditions. A
      working hypothesis is put forward, which is centered on the preformation of
      capillary lumen as a "tunnel" drilled by penetrating MC/Mph. The tunnels may be
      colonized in a later stage by sprouts, circulating progenitor endothelial cells
      (CPEC) or transdifferentiated EC. Thus, MC/Mph are suggested to be included among
      the targets of therapeutic manipulation of angiogenesis.

PMID- 11983093
TI  - The role of the stem cell leukemia (SCL) gene in hematopoietic and endothelial
      lineage specification.
AB  - Anatomical observations made at the beginning of the twentieth century revealed
      an intimate association between the ontogeny of blood and endothelium and led to
      the hypothesis of a common cell of origin termed the hemangioblast. However, the
      precise nature of the cellular intermediates involved in the development of both
      lineages from uncommitted precursors to mature cell types is still the subject of
      ongoing studies, as are the molecular mechanisms driving this process. There is
      clear evidence that lineage-restricted transcription factors play a central role
      in the genesis of mature lineage committed cells from multipotent progenitors.
      Amongst these, the basic helix-loop-helix (bHLH) family is of key importance for
      cell fate determination in the development of the hematopoietic system and
      beyond. This article will review the current evidence for the common origin of
      blood and endothelium, focusing on the function of the bHLH protein encoded by
      the stem cell leukemia (SCL) gene, and its role as a pivotal regulator of
      hematopoiesis and vasculogenesis.

PMID- 11983094
TI  - Vasculogenesis and the search for the hemangioblast.
AB  - Embryonic endothelial cells (EC) are generated by two mechanisms, vasculogenesis
      and angiogenesis (1). The term vasculogenesis describes the de novo emergence of
      EC progenitors from the mesoderm, whereas angiogenesis corresponds to the
      generation of EC by sprouting from the pre-existing vascular network. Until
      recently, it was thought that vasculogenesis was restricted to the period of
      embryonic development, whereas in the adult, only angiogenesis contributed to EC
      proliferation. The discovery of circulating EC progenitors in adult bone marrow
      and peripheral blood has suggested that additional mechanisms besides
      angiogenesis can occur in the adult, and therefore have renewed interest in the
      embryonic origin and the development of these progenitor cells. Vasculogenesis in
      the chick embryo has been studied since the beginning of the 20th century. During
      early development, vasculogenesis is intimately linked to the emergence of
      hematopoietic cells (HC). The existence of a common precursor for both EC and HC,
      termed "hemangioblast," was postulated (2). The purpose of this review is to
      summarize the experimental evidence concerning the emergence of EC and HC during
      embryonic life.

PMID- 11983095
TI  - A systematic approach to hepatic complications in hematopoietic stem cell
      transplantation.
AB  - Hepatic injury is a common complication of hematopoietic stem cell
      transplantation (HSCT) and carries a high risk of early morbidity and mortality.
      Evaluation of the patient for hepatic complications should begin in the
      pretransplant period with the identification of pretransplant risk factors, such
      as hepatitis status, that may predict severe liver complications and continue
      through the early and late transplant periods. Early hepatic complications
      include drug toxicity, hepatic veno-occlusive disease (VOD), acute graft-versus
      host disease (GVHD), infection, and cholestatic disorders. With increased
      survival of HSCT recipients, long-term liver complications from chronic viral
      hepatitis, chronic GVHD, and iron overload are being reported. The diagnosis and
      management of hepatic disorders in transplant can be complex, because one must
      decide whether a given symptom is due to one or a combination of diverse causes.
      Making the diagnosis can be crucial, because specific therapies can improve one
      condition but worsen another. This review describes a systematic approach to the
      evaluation of HSCT patients with hepatic complications with an emphasis on the
      need to intervene early with radiologic imaging and liver biopsy. Updated
      treatment options are also discussed. It is hoped that a standard approach will
      help to streamline clinical management of these very complex patients.

PMID- 11983096
TI  - Emergence of multidrug resistance in leukemia cells during chemotherapy:
      mechanisms and prevention.
AB  - Multifactorial resistance to extracellular stimuli is one of the major factors of
      tumor progression. Cells can acquire a multidrug resistant (MDR) phenotype in
      response to a wide variety of stress-inducing agents including chemotherapeutic
      drugs. In addition to the mechanisms expressed in the tumor prior to chemotherapy
      (presumably these mechanisms allowed tumor cells to escape the control of growth
      and differentiation), a complex phenotype of pleiotropic resistance is presented
      in the residual or recurrent tumor. This review analyzes the molecular mechanisms
      of MDR acquisition with the focus on hematopoietic malignancies. In particular,
      the chemotherapy-induced up-regulation of P-glycoprotein, a broad-specificity
      transmembrane efflux pump, is considered a major event in establishment of MDR in
      leukemia cells that were sensitive before drug exposure. The pharmacological and
      genetic approaches to prevent the acquisition of Pgp-mediated MDR during
      chemotherapy are discussed.

PMID- 11983097
TI  - Nonmyeloablative allogeneic hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective
      treatment for selected hematological malignancies. Its curative potential is
      largely mediated by an immune-mediated destruction of malignant cells by donor
      lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its
      toxicity, conventional allogeneic HSCT is restricted to younger and fitter
      patients. These observations led several groups to set up new (less toxic)
      transplant protocols (nonmyeloablative stem cell transplantation or NMSCT) based
      on a two-step approach: first, the use of immunosuppressive (but
      nonmyeloablative) preparative regimens providing sufficient immunosuppression to
      achieve engraftment of allogeneic hematopoietic stem cells and, in a second step,
      destruction of malignant cells by the GVL effect. Preliminary results showed that
      NMSCT were feasible with a relatively low transplant-related mortality (TRM),
      even in patients older than 65 years. In addition, strong antitumor responses
      were observed in several hematological malignancies as well as in some patients
      with renal cell carcinoma. After discussing the mechanisms and efficacy of the
      GVL effect as well as the rationale for NMSCT strategies, this article reviews
      the first results of ongoing clinical trials. Innovative modalities that may
      permit amplification of the GVL effect while minimizing the risk of GVHD are
      discussed. Because the benefits of NMSCT over alternative forms of treatment
      remain to be demonstrated, this strategy should be restricted to patients
      included in clinical trials.

PMID- 11983098
TI  - Donor lymphocyte infusion: the use of alloreactive and tumor-reactive lymphocytes
      for immunotherapy of malignant and nonmalignant diseases in conjunction with
      allogeneic stem cell transplantation.
AB  - Donor lymphocyte infusion (DLI), pioneered in Jerusalem in January 1987,
      represents the first proof of principle of the absolute efficacy of immunotherapy
      as a means of curing cancer. Immunotherapy with alloreactive donor lymphocytes
      can eliminate "the last tumor cell" even in patients with hematological
      malignancies resistant to maximally tolerated doses of chemoradiotherapy.
      Alloreactive lymphocytes that can mediate anti-tumor effects following induction
      of host-versus-graft tolerance induced by transplantation of donor stem cells,
      can induce graft-versus-malignancy (GVM) effects which are usually accompanied by
      graft-versus-host disease (GVHD). However, occasionally GVM effects may also be
      accomplished independently of clinically overt GVHD. Interestingly, allogeneic
      donor lymphocytes may also eliminate undesirable host-derived hematopoietic cells
      in a large number of nonmalignant indications including genetic diseases,
      diseases caused by deficiency of stem cell products, and autoimmune disorders
      mediated by self-reactive lymphocytes. The cumulative clinical experience
      suggests feasibility of effective induction of graft-versus-leukemia (GVL); graft
      versus-lymphoma (GVLy); graft-versus-multiple myeloma, as well as graft-versus
      solid tumors (GVT), well-documented in patients with renal and breast cancer,
      even in patients with resistant disease that have failed myeloablative
      chemoradiotherapy. These observations that suggested that cell therapy by donor
      lymphocytes is the main therapeutic benefit of bone marrow transplantation (BMT)
      led to development of the nonmyeloablative approach for safer allogeneic stem
      cell transplantation. Nonmyeloablative stem cell transplantation (NST) makes it
      possible to offer an option for cure to elderly patients with no upper age limit,
      as well as to patients with poor performance status not considered eligible for
      conventional BMT. Using well-tolerated NST regimen, allogeneic stem cell
      transplantation can be accomplished with minimal procedure-related toxicity and
      mortality, possibly even on an outpatient basis. Immunotherapy mediated by
      adoptive allogeneic cell-mediated immunotherapy can be further improved by
      utilizing specifically immune donor lymphocytes, thus maximizing their efficacy
      against undesirable target cells of host origin on the one hand, while minimizing
      their ontoward efficacy against normal cells of host origin that could result in
      GVHD on the other. Taken together, DLI and subsequently NST, may have opened new
      horizons for treatment of life-threatening malignant and nonmalignant disorders
      correctable by allogeneic stem cell transplantation. It is anticipated that
      further improvement of reactivity and specificity of donor lymphocytes will lead
      to safer clinical application of cell therapy for a larger number of indications
      toward improving disease-free survival in a large number of indications while
      minimizing immediate and late procedure-related complications.

PMID- 11983099
TI  - Increased risk of lethal graft-versus-host disease-like syndrome after
      transplantation into NOD/SCID mice of human mobilized peripheral blood stem
      cells, as compared to bone marrow or cord blood.
AB  - We tested the ability of human cells from different hematopoietic tissues to
      generate graft versus host disease-like syndrome (GVHD) in sublethally irradiated
      non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tissue
      sources of human hematopoietic cells were: (1) bone marrow (BM), (2) nonmobilized
      peripheral blood (PB), (3) mobilized peripheral blood stem-progenitor cells
      (PBSC), and (4) cord blood (CB). To avoid interindividual donor variation, part
      of this study was done using BM, PB, and PBSC donated by a single healthy adult
      volunteer. A total of 179 NOD/SCID mice received graded human hematopoietic cell
      doses [5-500 x 10(6) mononuclear cells (MNC), containing 2-325 x 10(6) CD3(+) T
      cells, per mouse] from individual donors. Mice were observed for the development
      of GVHD and sacrificed 60 days after transplantation (earlier if ill). Mice were
      analyzed quantitatively by flow cytometry for human hematopoietic cell types and
      histologically, especially for human T lymphocytes infiltrating BM. No mouse
      transplanted with the tested doses of human CB or BM cells developed GVHD
      (experimentally defined as >10% human T lymphocytes infiltrating the mouse BM).
      For PB and PBSC, the frequencies of death, death with GVHD, and GVHD were
      directly related to the dose and source of human cells. Because PB cells
      contaminate harvested BM, the results from infused BM and PB were next combined
      for further analysis (BM/PB). The relative risks (hazard ratios estimated from
      the proportional hazards model) for death with GVHD, for each 10 human T cell
      dose increase, were 1.15 for BM/PB (p < 0.0001) and 1.47 for PBSC (p < 0.0001).
      In this in vivo xenogeneic model, the average T cell from human PBSC generated
      GVHD more potently than did the average T cell from human BM/PB, and the average
      CB T cell had a much lower GVHD potential. These results suggest that the
      potential for clinical GVHD from an HLA-disparate donor graft is likely to be
      quantitatively dependent both on the total number of T lymphocytes in the donor
      graft and the tissue source of the graft. Quantitative criteria for optimal T
      cell content of allogeneic donor hematopoietic grafts from different sources are
      discussed.

PMID- 11983100
TI  - High-dose hydroxyurea plus G-CSF mobilize BCR-ABL-negative progenitor cells (CFC,
      LTC-IC) into the blood of newly diagnosed CML patients at any time of
      hematopoietic regeneration.
AB  - The objective of this study was to analyze the mobilization kinetics of normal
      (BCR-ABL(neg)) and malignant (BCR-ABL(pos)) progenitor cells using a new, low
      toxic, out-patient-based mobilization regimen for Philadelphia chromosome
      positive (Ph(pos)) chronic myelogenous leukemia (CML) patients. High doses of
      hydroxyurea (HD-HU, 3.5 g/m(2) per day, orally for 7 days) followed by
      granulocyte colony-stimulating factor (G-CSF) (10 microg/kg subcutaneously) were
      administered to 11 newly diagnosed CML patients. Each apheresis product (n = 30)
      was individually analyzed for the number and genotype of mature colony-forming
      cells (CFC) and primitive long-term culture initiating cells (LTC-IC),
      respectively, by reverse transcription polymerase chain reaction (RT-PCR) of
      individual colonies. Sufficient numbers of CD34(+) cells/kg bodyweight (BW) could
      easily be obtained in all patients (median, 15 x 10(6)/kg BW per patient) with a
      median number of three aphereses performed per patient (range 2-4). Almost each
      apheresis itself (25/30) contained > or =2 x 10(6) CD34(+) cells/kg BW. All
      patients with low and intermediate Sokal risk indices (9/11) mobilized primarily
      BCR-ABL(neg) LTC-IC (median 92%, range 47-100) and CFC (median 89%, range 57
      100). Moreover, the mean percentage of BCR-ABL(neg) CFC and LTC-IC in the various
      apheresis products in these patients did not change throughout the entire time of
      hematopoietic regeneration. The toxicity of the mobilization procedure was low.
      Side effects were mild erythema in 8/11 and oral mucositis in 3/11 patients.
      Overall, the low toxicity of this regimen, together with the fact that sufficient
      BCR-ABL(neg) progenitors can be collected throughout the entire period of
      hematopoietic regeneration, renders this mobilization regimen particularly
      attractive for the collection of BCR-ABL(neg) progenitors in early chronic phase
      of Ph(pos) CML.

PMID- 11983101
TI  - Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected
      peripheral blood stem cells.
AB  - To decrease the incidence of graft-versus-host disease (GVHD) observed after
      nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of
      CD8-depleted or CD34-selected NMSCT followed by CD8-depleted preemptive donor
      lymphocyte infusion (DLI) given in incremental doses on days 40 and 80. Fourteen
      patients with high-risk malignancies and an HLA-identical sibling (n = 8) or
      alternative donor (n = 6) but ineligible for a conventional transplant were
      included. Nonmyeloablative conditioning regimen consisted in 2 Gy total body
      irradiation (TBI) alone, 2 Gy TBI and fludarabine (previously untreated patients)
      or cyclophosphamide and fludarabine (patients who had previously received > or
      =12 Gy TBI). Patients 1-4 (controls) received unmanipulated peripheral blood stem
      cells (PBSC) and DLI and patients 5-14 CD8-depleted or CD34-selected PBSC
      followed by CD8-depleted DLI. Post-transplant immunosuppression was carried out
      with cyclosporine A (CsA) and mycophenolate mofetil (MMF). Initial engraftment
      was seen in all patients, but 1 patient (7%) later rejected her graft. The
      actuarial 180-day incidence of grades II-IV acute GVHD was 75% for patients 1-4
      versus 0% for patients 5-14 (p = 0.0019). Five of 14 patients were in complete
      remission (CR) 180 days after the transplant and 6/14 had partial responses. The
      1-year survival rate was 69%, and nonrelapse and relapse mortality rates were 16
      and 18%, respectively. We conclude that CD8-depleted or CD34-selected NMSCT
      followed by CD8-depleted DLI is feasible and considerably decreases the incidence
      of acute GVHD while preserving engraftment and apparently also the graft-versus
      leukemia (GVL) effect. Further studies are needed to confirm this encouraging
      preliminary report.

PMID- 11983102
TI  - In vivo purging with rituximab prior to collection of stem cells for autologous
      transplantation in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) cells express the CD20 antigen, and monoclonal
      antibodies against CD20 have resulted in remissions. We hypothezised that the
      anti-CD20 antibody rituximab (Rituxan) may be useful in reducing the number of
      contaminating CLL cells in stem cell collections for use in autologous
      transplantation. A pilot study in 5 patients was designed using rituximab 375
      mg/m(2) as an in vivo purging step following cyclophosphamide 4 gm/m(2) and
      granulocyte colony-stimulating factor/granulocyte-macrophage colony-stimulating
      factor (G-CSF/GM-CSF) mobilization therapy for patients with advanced-stage CLL
      undergoing autologous stem cell transplantation. Eligible patients had 0-30%
      marrow involvement prior to mobilization. A single pre-rituximab leukapheresis
      product was obtained after the white blood cells (WBC) reached 800/mm(3) to serve
      as a control but was not reinfused. Rituximab was administered the following day
      and subsequent leukaphereses were commenced 48 h later to reach a total of >2 x
      10(6) CD34(+) cells/kg. Dual-color flow cytometry CD5/CD19 and consensus PCR
      using primers to the joining region and FR3 of the variable region of the
      immunoglobulin heavy chain (IgH) were used to evaluate the degree of
      contaminating CLL cells in the leukapheresis product and to monitor disease
      status post transplant. All 5 patients were informative for the consensus PCR
      assay. Four of 5 patients mobilized >2 x 10(6) CD34(+) cells/kg and proceeded to
      cyclophosphamide 120 mg/kg and total body irradiation (6 x 200 cGy) with stem
      cell rescue. All leukaphereses products were positive by PCR for the IgH
      rearrangement and 4/5 contained CD5/CD19 dual-positive cells. Comparing the pre-
      and post-rituximab leukapheresis products, a reduction in the percentage of
      CD5(+)/CD19(+) cells was seen in 4/5 patients. All patients engrafted at a median
      of 13.5 days to ANC > 500/mm(3) and 11 days to platelets >20,000/mm(3). No
      regimen-related mortality was seen. Although 2 patients tested positive on PCR
      for the IgH rearrangement early after transplant, all patients had absence of the
      IgH gene rearrangement at 1 year and no CD5/CD19 dual-positive cells were could
      be detected in the bone marrow. This includes 1 heavily pretreated patient who
      received stem cells containing up to 30% CD5(+)/CD19(+) cells. We conclude that
      purging with Rituximab 48 h prior to stem cell collection was able to reduce
      significantly (but not eliminate) the percentage of CLL cells in the
      leukaphereses. However, despite the infusion of CD5(+)/CD19(+) cells in the stem
      cell coions, patients were able to obtain durable complete molecular remissions,
      implying that the PCR-positive cells in the leukaphereses may not have long-term
      clonogenic potential. The results also support the recommendation to test if
      rituximab should be part of a maintenance regimen after transplant to prevent
      disease recurrence in high-risk patients.

PMID- 11983103
TI  - Correlation of time to platelet engraftment with amount of transplanted
      CD34+CD41+ cells after allogeneic bone marrow transplantation.
AB  - A major problem after autologous or allogeneic stem cell transplantation is
      prolonged thrombocytopenia. There are several studies published about
      correlations of the composition of the graft and time to platelet engraftment for
      autologous transplantation but only a few studies for allogeneic transplantation.
      In our study, we wanted to find out whether the correlation between the time to
      platelet engraftment and amount of transplanted CD34(+)CD41(+) cells described
      previously after autologous peripheral blood stem cell transplantation could be
      reproduced in the allogeneic bone marrow transplantation setting. We found
      correlations not only for the number of transplanted CD34(+) cells with the time
      to leukocyte engraftment (r = -0.32, p = 0.045) but also for the number of
      transplanted CD34(+)CD41(+) cells and time to platelet engraftment (r = -0.34, p
      = 0.038), which were both statistically significant. A significant correlation
      between transplanted CD34(+) cells versus platelet engraftment and transplanted
      CD34(+)CD41(+) cells versus leukocyte engraftment was not found. The finding that
      the amount of committed megakaryocyte progenitor cells in the graft is an
      important predictive factor for platelet engraftment after allogeneic bone marrow
      transplantation might be the base for future studies of ex vivo expansion of
      clonable megakaryocyte precursors.

PMID- 11983104
TI  - Successful transduction of human multipotent, lymphoid (T, B, NK) and myeloid,
      and transplantable CD34+CD38low cord blood cells using a murine oncoretroviral
      vector.
AB  - Hematopoietic stem cells (HSC) are subject to great interest because of their
      medical importance and their biological properties. Therefore, the possibility of
      genetically modifying human HSC is a major concern in several inherited
      pathologies. In this study, we aimed to demonstrate that a murine oncoretroviral
      vector can transduce multipotential cord blood (CB) stem cells. Sorted CB
      CD34(+)CD38(low) cells were transduced with a Moloney-based MFG retroviral vector
      containing the coding sequence of the murine CD2 (mCD2). CD34(+)mCD2(+) cells
      were sorted by flow cytometry and cultured either in bulk or at one cell per well
      in culture conditions that allow differentiation along lymphoid (T, B, and NK)
      and myeloid (M) lineages. Phenotypic analysis of cells generated in culture
      showed that CD34(+)mCD2(+) cells could give rise to all lymphoid and myeloid
      progeny, indicating that the MFG/mCD2 vector had transduced progenitors of all
      tested lineages. Moreover, clonal cultures of 660 CD34(+)mCD2(+) cells showed
      that approximately 5% of these cells were able to generate both myeloid and
      lymphoid (B + NK) progenies; for 25% of them, this included the production of
      lymphoid T cells. We also demonstrate that transduced CD34(+)CD38(low) CB cells
      with lymphoid and myeloid potentials were capable of engraftment into the bone
      marrow (BM) of nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice
      during several months. These results show that MFG retroviral vectors can
      transduce multipotent (T, B, NK, M) human hematopoietic progenitors with in vivo
      repopulating activity.

PMID- 11983105
TI  - Comparison of phenotypic and functional dendritic cells derived from human
      umbilical cord blood and peripheral blood mononuclear cells.
AB  - Dendritic cells (DC) are important accessory cells that are capable of initiating
      an immune response. Generation of functional DC has potential clinical use in
      treating diseases such as cancer. In this report, we have demonstrated the
      generation of functional DC from mononuclear cells isolated from human umbilical
      cord blood cells (UCBC) and peripheral blood cells (PBC) using a defined medium
      Prime Complete Growth Medium (PCGM) (GenePrime LLC, Gaithersburg, MD). DC
      generated using PCGM showed the typical phenotype of DC as determined by flow
      cytometry and electron microscopy. Further analysis of the DC using confocal
      microscopy showed localization of the antigen and major histocompatibility
      complex (MHC) molecules in the cytoplasm 3-5 days following tumor antigen loading
      into DC. Subsequently, the tumor antigen-MHC complex was localized on the surface
      of DC. DC generated from UCBC or PBC also increased (p < 0.001) the allogeneic
      mixed lymphocyte reaction, confirming their immune accessory functions compared
      to a control mixed lymphocyte reaction (MLR) without DC added. Interestingly, DC
      generated using PCGM medium also significantly enhanced the hematopoietic colony
      (CFU-C)-forming ability. Furthermore, addition of 5% DC derived from cord blood
      loaded with tumor antigen also significantly (p < 0.001) increased peripheral and
      cord blood-derived antigen-specific cytotoxic T lymphocyte (CTL)-mediated killing
      of human leukemic cells (K562) and breast cancer cells (MDA-231). Thus, these
      results show that functional DC generated from cord blood using a defined medium
      are a useful source of accessory cells for augmenting CTL-mediated cytotoxicity
      and have potential use in cellular therapy for human leukemia and breast cancer.

PMID- 11983106
TI  - Clinical relevance of minimal residual disease detection in adult acute myeloid
      leukemia.
AB  - We have used flow cytometry to quantify minimal residual disease (MRD) in 63
      patients with acute myeloid leukemia (AML). No significant correlation was found
      between the level of MRD after induction and disease outcome. After
      consolidation, a threshold of 3.5 x 10(-4) residual leukemic cells divided the 57
      evaluable patients into two distinct groups: the MRDCons(+) and the MRDCons(-)
      group, with a relapse rate of 81% (22/27) and 27% (8/30), respectively (p =
      0.000035). Although not correlated with prognosis, the level of MRD after
      induction course affected the degree of cytoreduction achieved with
      consolidation. In fact, the patients who entered a MRDCons(-) status had a median
      number of leukemic residual cells of 1.8 x 10(-4) after induction; at the same
      stage, the bone marrow of patients who were in a MRDCons(+) condition harbored a
      median level of 1.7 x 10(-3) malignant residual cells (p = 0.00073). The
      MRDCons(+) status also correlated significantly with poor/intermediate risk
      cytogenetics, MDR1 phenotype, short duration of overall survival, and relapse
      free survival (p = 0.024, 0.021, 0.00001, and 0.00001, respectively). In
      multivariate analysis, the MRDCons(+) status was associated with a high
      probability of relapse (p < 0.00026) and short duration of relapse free survival
      (p = 0.008). Stem cell transplantation did not seem to alter the prognostic
      impact of high levels of MRD after consolidation: within the MRDCons(+) group,
      the relapse rate after transplant was 78%. Thus, a MRD > or = 3.5 x 10(-4)
      leukemic cells at the end of consolidation strongly predicts relapse, and is
      significantly associated with MDR1-positive phenotype and
      intermediate/unfavorable cytogenetics.

PMID- 11983107
TI  - Quantitative and qualitative analysis of the human primitive progenitor cell
      compartment after autologous stem cell transplantation.
AB  - The aim of this study was to examine whether the severe prolonged deficiency in
      marrow clonogenic progenitor cells reported after autologous stem cell
      transplantation (ASCT) is associated with impairment of the primitive progenitor
      cell compartment. We performed Dexter-type marrow cultures and limiting dilution
      assays with CD34(+) cells from patients 1 year and/or later after autografting
      with peripheral blood stem cells for non-Hodgkin's lymphoma (NHL). Flow
      cytometric analysis was used to assess the CD38 antigen expression and apoptotic
      state (7-ADD(-)/annexin-V(+) cells) of the CD34(+) cell population. We found a
      dramatic decrease in both clonogenic progenitor cell production and frequency of
      long term culture-initiating cells (LTC-IC) in all the patients tested at 1 year,
      even in those displaying normal progenitor cell frequency. Surprisingly, the
      clonogenic capacity of each LTC-IC was not increased. Flow cytometric analysis of
      the CD34(+) cell population confirmed this quantitative defect, with a reduction
      in the CD38(dim/neg) cell population but no increase in apoptosis. This defect
      did not improve over time up to 4 years after transplantation. In addition,
      qualitative abnormalities were revealed, demonstrated by decreased CD34 antigen
      expression, together with impaired differentiating properties of LTC-IC toward
      erythroid lineage at 1 year. This study indicates that both quantitative and
      qualitative abnormalities of the primitive progenitor cell compartment are a
      constant feature up to 4 years after autologous stem cell transplantation.

PMID- 11983108
TI  - Increased erythrocyte glutathione peroxidase activity and serum tumor necrosis
      factor-alpha in HIV-infected patients: relationship to on-going prothrombotic
      state.
AB  - A condition of oxidative stress, due to perturbation of oxidant/antioxidant
      balance, has been suggested to play a role not only in the pathogenesis of human
      immunodeficiency virus (HIV) infection, but also in the promotion of a
      thrombophilic condition. Because various hemostatic dysfunctions usually
      considered as risk factors for thrombotic events were reported in HIV infection,
      this study was undertaken to investigate whether the oxidative phenomenon could
      promote a prothrombotic state in such condition. Erythrocyte glutathione
      peroxidase (GSH-Px), the major free-radical scavenger enzyme, and serum tumor
      necrosis factor-alpha (TNF-alpha) were evaluated in 33 consecutive HIV-infected
      out-patients and 35 matched HIV-negative healthy controls at a distance of any
      acute episode. Thrombin generation was explored by measuring the plasma levels of
      prothrombin fragment 1 + 2 (F1 + 2), whereas fibrin degradation products (D
      dimer) and plasminogen activator inhibitor (PAI-1) activity were evaluated as
      indices of plasmin activity and fibrinolytic derangement. The anticoagulant
      pathway was investigated by measuring the plasma levels of antithrombin and
      protein C. Erythrocyte GSH-Px activity and serum TNF-alpha were significantly
      higher in HIV-infected patients when compared to controls. F1 + 2, D-dimer, and
      PAI-1 activity were increased in HIV-infected patients by comparison with
      controls. Normal antithrombin, but decreased protein C, was instead detected in
      HIV-infected patients. In the latter patients, serum TNF-alpha negatively
      correlated with both erythrocyte GSH-Px activity and plasma D-dimer. On the other
      hand, a positive correlation was shown between F1 + 2 and D-dimer and between D
      dimer and GSH-Px activity. Furthermore, a trend toward increasing levels of GSH
      Px with increasing PAI-1 activity was reported. These findings suggest a
      relationship between erythrocyte oxidative stress and the hypercoagulable
      condition during HIV infection.

PMID- 11983109
TI  - Bone marrow transplantation for nonmalignant diseases.
AB  - Bone marrow transplantation (BMT) has emerged as a major therapeutic option for a
      number of nonmalignant disorders affecting the bone marrow and leading to
      clinical manifestations most likely affecting distant organs. Disorders such as
      autoimmune diseases, metabolic disorders, hemoglobinopathies, immunodeficiencies,
      and others have been the target of high-dose therapy and autologous or allogeneic
      bone marrow, stem cell, or cord blood transplantation. Successful results have
      been reported in a large number of these disorders. In most instances the goal of
      transplantation is to provide sufficient degree of marrow engraftment to allow
      long-term amelioration of disease phenotype. For many of these disorders, early
      diagnosis is crucial in achieving the desired results as transplantation becomes
      difficult when significant end-organ damage sets in. Major unsolved problems,
      including toxicity of conditioning regimens, graft-versus-host disease, and donor
      availability, need to be addressed. We attempt to provide a comprehensive review
      of BMT and discuss unique features of this modality for treatment of nonmalignant
      disorders.

PMID- 11983110
TI  - Flt3/Flk-2-ligand in synergy with thrombopoietin delays megakaryocyte development
      and increases the numbers of megakaryocyte progenitor cells in serum-free
      cultures initiated with CD34+ cells.
AB  - Megakaryocytopoiesis involves proliferation and maturation of committed
      precursors that increase their size by polyploidy, a process that is believed to
      be critical for the efficient production and release of platelets. Thrombopoietin
      has been shown to act on proliferation, maturation, and survival pathways in
      megakaryocytopoiesis. Less is known about the role of Flt3/Flk-2-ligand in this
      development. Apoptosis has an important role in hematopoiesis in general. It has
      been shown to have an effect on senescent megakaryocytes but not megakaryocyte
      progenitor cells. In this study, a serum-free culture model was developed,
      differentiating bone marrow CD34(+) hematopoietic stem cells into megakaryocytes,
      using thrombopoietin and Flt3/Flk-2-ligand. The model was used to study the
      effect of these growth factors on expansion of megakaryocyte progenitor cells,
      differentiation of megakaryocytes, and ploidy. Our results demonstrate that bone
      marrow CD34(+) cells cultured with thrombopoietin and Flt3/Flk-2-ligand show a
      lower developmental rate into MK cells compared to cells cultured with
      thrombopoietin alone. Cells cultured with thrombopoietin and Flt3/Flk-2-ligand
      expressed less CD41, the ploidy level was lower, and they appeared less mature.
      On the other hand, the cells showed up to 10-fold increase in cell numbers
      compared to five-fold increase when cultured with thrombopoietin alone. These
      results suggest that Flt3/Flk-2-ligand in synergy with thrombopoietin may slow
      down megakaryocyte development by causing increased proliferation of
      megakaryocyte progenitor cells.

PMID- 11983111
TI  - Analysis of the nuclear distribution of the translocation t(8;21)-derived fusion
      protein AML1/ETO by confocal laser scanning microscopy.
AB  - The AML1/ETO protein derived from the t(8;21) translocation retains the DNA
      binding domain of AML1, the runt homology domain (RHD), and nearly the complete
      ETO protein with its four nervy homology regions (NHR1-4). To analyze which
      domains of AML1/ETO are responsible for its intranuclear transport and its
      subnuclear distribution, AML1/ETO deletion constructs tagged with green
      fluorescence protein were expressed transiently in 293 cells. The subcellular
      distribution was analyzed by confocal laser scanning microscopy. The nuclear
      localization signal (NLS) of AML1/ETO was mapped to a region encoded by the
      carboxy-terminal part of NHR1 and the sequences following up to NHR2
      corresponding to the amino acids 304-489 of the AML1/ETO protein. A speckled
      subnuclear distribution was found with those constructs containing the NHR2
      and/or the NHR3 and NHR4 domains. Co-localization with AML1/ETO was complete with
      constructs containing the NHR2 domain, indicating that NHR2 has a crucial role in
      the subnuclear distribution of AML1/ETO. Co-localization with AML1 seems to be
      supported by RHD, whereas the NHR3 and NHR4 regions possibly counterbalance this
      effect. Finally, AML1/ETO could not be co-localized with PML and SUMO-1,
      indicating that AML1/ETO is not part of the nuclear bodies and probably not
      SUMOylated.

PMID- 11983112
TI  - A lesson for unraveling complex aspects of novel immunodeficiencies from the
      human equivalent of the nude/SCID phenotype.
AB  - The human equivalent form of the severe combined congenital immunodeficiency of
      the nude/SCID mouse has been recently described in 2 siblings originating from a
      small community in southern Italy. Similar to the mouse, the human phenotype is
      characterized by a profound T cell ontogenetic defect associated with congenital
      alopecia and nail dystrophy. The disease is related in either mice and humans to
      molecular alterations of the gene encoding a forkhead/winged helix transcription
      factor, which is selectively expressed in thymic epithelia. Remarkably, due to
      the selectivity of the tissue expressivity of the gene responsible for the
      syndrome, this is the first example of SCID not primarily related to an
      hematopoietic cell abnormality, but rather to thymic aplasia. The opportunity to
      study immunological reconstitution in the absence of a functioning thymus
      following a bone marrow transplantation from a related HLA-identical sibling gave
      us insight into the role of the thymus in in vivo T cell ontogeny and maintenance
      of T cell functionality. This model led us to address a few general issues that
      may have clinical implications.

PMID- 11983113
TI  - Mobilization of peripheral blood stem cells with paclitaxel and rhG-CSF in high
      risk breast cancer patients.
AB  - Preclinical studies have demonstrated the rapid and efficient mobilization of
      hematopoietic peripheral blood stem cells (PBSC) in a mouse model using the
      combination of paclitaxel with recombinant human granulocyte colony-stimulating
      factor (rhG-CSF). On the basis of these results, a clinical trial was initiated
      using rhG-CSF with paclitaxel for PBSC mobilization in high-risk breast cancer
      patients. The mobilized PBSC were evaluated for CD34(+) cell number, mononuclear
      cell content, and clonogenic potential. One-hundred and seventeen breast cancer
      patients received paclitaxel (300 mg/m(2)) administered as a 24-h continuous
      intravenous infusion. Forty-eight hours after completing paclitaxel, rhG-CSF (5
      microg/kg) was initiated and continued until completion of PBSC collection.
      Leukapheresis was initiated once the white blood cell count reached 1.0 x
      10(9)/L. Each collection was evaluated for the numbers of mononuclear cells (MNC)
      and CD34(+) cells. Clonogenic potential was enumerated using colony-forming units
      granulocyte-macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E).
      Patients receiving paclitaxel with rhG-CSF mobilized a large number of
      mononuclear cells/apheresis (mean, 3.7 x 10(8); range, 3.3-4.1) and CD34(+)
      cells/apheresis (mean, 7.2 x 10(6); range, 6.1-8.4). The average number of
      leukophereses needed was 1.8 (mean, range 1.6-2.0). Colony growth was normal with
      178.9 x 10(5) and 214.8 x 10(5) colonies counted in CFU-GM and BFU-E assays,
      respectively. Patients engrafted platelets and neutrophils on day 10 following
      transplantation. In conclusion, PBSC mobilization with paclitaxel and rhG-CSF
      results in a large number of mononuclear cells and CD34(+) cells with normal
      clonogenic potential. The cells engraft normally following high-dose chemotherapy
      and autologous stem cell transplantation in high-risk breast cancer patients.
      These results demonstrate that paclitaxel with rhG-CSF is an efficient mobilizing
      agent in high-risk breast cancer patients.

PMID- 11983114
TI  - Gene profiling in anaplastic large-cell lymphoma-derived cell lines with cDNA
      expression arrays.
AB  - Comparative hybridization of cDNA arrays is a powerful high-throughput tool for
      the measurement of gene expression between two or more tissues. Moreover, cDNA
      array technology permits detection of genes involved in carcinogenesis and
      prospective targets for diagnosis or therapy in the future. We used this
      technique in cell lines to discover genes possibly involved in the pathogenesis
      of the large-cell anaplastic lymphoma (ALCL). CD30(+) lymphoma cells are
      characteristic for this lymphoma entity and were first described 16 years ago.
      Still, little is known about the biology of this aggressive lymphoma. Identical
      arrays covering 1176 genes (Clontech Human Cancer 1.2) were hybridized with
      labeled first-strand cDNA from five ALCL cell lines and stimulated T cells. We
      found overlapping gene expression patterns in the five cell lines. Three genes,
      tissue inhibitor of metalloproteinases 1 (TIMP-1), nm23-H4, and interferon
      induced 56K protein (IFI-56K) were strongly overexpressed in all ALCL cell lines
      compared with stimulated T cells. Whereas interleukin-2 precursor, interleukin-9
      precursor, interferon-gamma precursor, T cell surface glycoprotein CD3 epsilon
      subunit, 40S ribosomal protein SA, and protein-tyrosine phosphate 1C were
      underexpressed, Reverse transcription polymerase chain reaction and Northern blot
      analysis were employed to confirm the expression patterns of the genes identified
      by Atlas hybridization.

PMID- 11983115
TI  - Flow cytometric CD34+ determination in stem cell transplantation: before or after
      cryopreservation of grafts?
AB  - Various attempts have been made to standardize and improve the reproducibility of
      flow cytometric determination of CD34+ hematopoietic progenitor cells. It is
      still not clear, however, whether the quantification of CD34+ cells in a stem
      cell graft should be done before or after cryopreservation. To address this
      issue, we investigated 78 unselected and 32 immunomagnetically selected
      autologous and allogeneic leukapheresis products (LA) before and after
      cryopreservation using pilot vials. Cell numbers were quantified within a
      Neubauer chamber, and CD34+ content was determined by flow cytometry; propidium
      iodide staining was used to exclude dead cells from analysis. Before freezing,
      the mean viable CD34 cell content in the unselected samples was 1.22% and
      increased after thawing to a mean of 2.16% of viable cells. Taking into account
      cell loss and cell death, the overall recovery of viable cells was 64.5%; all
      CD34+ cells could be recovered. Mean purity in the CD34-selected cell fraction
      was 85% (48-97) before and 91.3% (67-99) after thawing. The number of viable
      cells was 86.8% before and 86.1% after freezing with a 93.9% recovery of total
      cells. This leads to a mean 93.7% (SD +/- 23.1) recovery of viable cells and 100%
      (SD +/- 22.3) recovery of viable CD34+ cells. There was no significant difference
      in tolerance to freeze/thaw stress between cells from heavily pretreated
      autologous patients and healthy allogeneic donors. Our data show that freezing
      significantly increases the percentage of CD34(+) cells in unmanipulated LA,
      probably due to the death of granulocytes and mononuclear cells (MNCs).
      Nevertheless, the overall number of viable CD34+ cells in unselected as well as
      selected samples remains unchanged. Thus, CD34 data from different laboratories,
      for example, within multicenter trials, should be comparable independent of the
      different time points of acquisition.

PMID- 11983116
TI  - Multifactorial drug resistance: P-glycoprotein on the apex of the pyramid.

PMID- 11983117
TI  - [Expression of activins, follistatin mRNA in the development of hepatic
      fibrosis].
AB  - OBJECTIVE: To examine the expression changes of activin beta A, beta C, beta E
      and follistatin mRNA in the development of rat hepatic fibrosis induced by carbon
      tetrachloride (CCl(4)). METHODS: Hepatic fibrosis was induced in rats by
      subcutaneous injections of 40% carbon tetrachloride oily solution for a period of
      1 to 7 weeks. After carbon tetrachloride injection of 1, 2, 3, 4, 5, 6, and 7
      weeks, the 6-12 rats were killed every time. The kinetics of activin beta A, beta
      C, beta E and follistatin mRNA expression were assessed by the semi-quantity RT
      PCR. RESULTS: Activin beta A, beta C, beta E and follistatin mRNA could be
      detected in normal rat livers. After CCl(4) injection for 2 or 3 weeks, beta A
      mRNA was transiently decreased and became undetectable, then increased gradually.
      After CCl injection for 6 and 7 weeks, beta A mRNA level was significantly higher
      than controls (P<0.01). beta C mRNA could be detected after CCl(4) injection for
      1 to 4 weeks and was significantly increased after 5 weeks over controls
      (P<0.05). beta E mRNA could not be detected after CCl(4) injection for 1 to 5
      weeks, but significantly increased after CCl(4) injection for 6 or 7 weeks
      compared with controls (P<0.01). Except for normal rat liver, no follistatin mRNA
      was detected in rats after CCl(4) injection. CONCLUSIONS: Activins and
      follistatin have different expression changes in the development of hepatic
      fibrosis and the imbalance of activins and follistatin expression may involve in
      the formation of hepatic fibrosis.

PMID- 11983118
TI  - [Effects of lamivudine and interferon-alpha combination therapy on chronic
      hepatitis B].

PMID- 11983119
TI  - [Expression of integrin alpha 6 in hepatic sinusoidal capillaration].
AB  - OBJECTIVE: To explore the expression of integrin alpha 6 in hepatic sinusoidal
      capillaration. METHODS: The rat hepatic fibrosis model was established by
      injection of carbon tetrachloride subcutaneously. Then the expression of laminin
      and integrin alpha 6 subunit was observed by immunohistochemistry and dot immuno
      blotting. RESULTS: We observed sinusoidal capillaration formed by deposition of
      laminin along sinusoids in Disse interspace by immunohistochemistry staining. In
      normal rat the expression of integrin alpha 6 was restricted to portal vascular
      endothelial cells and bile duct epithelial cell membranes. No expression was
      observed in sinusoidal endothelial cell membranes. When capillaration integrin
      alpha 6 was detected in a continuous pattern along the sinusoids, the content of
      integrin alpha 6 was significantly higher in fibrotic liver tissues than in
      normal liver tissues as measured by dot immuno-blotting (P<0.05). CONCLUSIONS:
      During fibrogenesis, laminin continuously accumulate in liver tissues and form
      basement membrane resulting in sinusoidal capillaration, and then induce the
      expression of integrin alpha 6 on SEC membranes.

PMID- 11983120
TI  - [Expression of CD(14) protein in liver sinusoidal endothelial cells during
      endotoxemia].
AB  - OBJECTIVE: To observe the expression of CD(14) protein and CD(14) gene in liver
      sinusoidal endothelial cells (LSECs) of rats during endotoxemia and the role of
      CD(14) protein in the activation of lipopolysaccharide (LPS)-induced LSECs.
      METHODS: Wistar rat endotoxemia model was established by injection of a dose of
      LPS (5 mg/kg, Escherichia coli O111:B4) via the tail vein of the rats, then
      sacrificed immediately, at 3, 6, 12, and 24 h, respectively. LSECs were isolated
      from normal and LPS-injected rats by the in situ collagenase perfusion technique.
      The isolated LSECs were incubated with anti CD(14) polyclonal antibody, then
      followed by staining with goat anti-rabbit IgG conjugated fluorescein
      isothiocyanate (FITC). The percentage and mean fluorescence intensity (MFI) of
      CD(14)-positive cells were detected by the flow cytometric analysis (FCM). LSECs
      were collected to measure the expression of CD(14) mRNA by the in situ
      hybridization analysis. The isolated LSECs from normal rats were divided into two
      groups. Group of LPS: LSECs were induced with different concentration of LPS (0,
      0.01 microg/ml, 1 microg/ml, 10 microg/ml, and 100 microg/ml). Group of anti
      CD(14) blockade: LSECs were pre-incubated for 30 min with CD(14) antibody before
      different concentrations of LPS were added. The supernatants of these cells were
      then collected for measuring the levels of tumor necrosis factor (TNF)- alpha and
      interleukin (IL)-6. RESULTS: In rats with endotoxemia, LSECs displayed a strong
      MFI distinct from that of control rats. The number of FITC-CD(14) positive LSECs
      was 54.32%, 65.83%, 85.61%, and 45.65% at 3, 6, 12, and 24 h, respectively, which
      increased markedly when compared to control rats (4.45%, P<0.01). The expression
      of CD(14) mRNA in LSECs was stronger than that in control rats. The levels of TNF
      alpha were significantly increased in group of LPS (54.49 +/- 6.02 pg/ml, 84.65
      +/- 10.16 pg/ml, 206.54 +/- 23.55 pg/ml, 349.87 +/- 39.47 pg/ml, and 365.76 +/-
      40.31 pg/ml) than those in group of anti-CD(14) blockade (55.93 +/- 6.95 pg/ml,
      63.32 +/- 7.81 pg/ml, 85.34 +/- 9.72 pg/ml, 112.75 +/- 13.54 pg/ml, and 198.66 +/
      21.54 pg/ml) (P<0.01). The levels of IL-6 also increased significantly in group
      of LPS (103.34 +/- 12.52 pg/ml, 187.39 +/- 20.31 pg/ml, 243.87 +/- 27.83 pg/ml,
      289.51 +/- 30.15 pg/ml, and 298.53 +/- 31.94 pg/ml) than those in group of anti
      CD(14) blockade (104.37 +/- 11.49 pg/ml, 125.02 +/- 13.58 pg/ml, 164.59 +/- 19.47
      pg/ml, 183.47 +/- 20.17 pg/ml, and 221.76 +/- 26.43pg/ml) (P<0.01). CONCLUSIONS:
      LSEC can synthesize CD(14) protein and express CD(14) gene during endotoxemia.
      Anti CD(14) antibody can inhibit the production of TNF-alpha and IL-6 in LSECs
      induced by LPS. The expression of CD(14) protein may take an important part in
      the activation of LSECs induced by LPS.

PMID- 11983121
TI  - [Vascular elasticity in patients with spontaneous rupture of hepatocellular
      carcinoma].

PMID- 11983122
TI  - [Reversing malignant phenotypes of liver cancer cell lines with antisense gene to
      human telomerase reverse transcriptase].
AB  - OBJECTIVE: To explore the effect of antisense gene to human telomerase reverse
      transcriptase (hTRT) on reversing malignant phenotypes of liver cancer cell
      lines. METHODS: Sense and antisense eukaryotic expressing vector of hTRT gene was
      transfected into human liver cancer line HepG(2) with the DOTAP liposomal
      transfection method. Changes of cellular malignant phenotypes through
      proliferation capacity, telomerase activity, cloning formation in soft agar,
      invasive capacity in Borden's chamber model and tumorigenicity in nude mice were
      examined. RESULTS: Sense and antisense eukaryotic expressing vector was
      successfully transfected into HepG(2). The obtained transfectants termed HepG(2)
      sense (HepG(2)-S) and HepG(2)-antisense (HepG(2)-AS) stably produced sense and
      antisense hTRT, respectively. HepG(2)-AS showed an obvious decrease in growth and
      telomerase activity. HepG(2)-AS penetrated cells through Matrigel were decreased
      significantly compared with HepG(2) and HepG(2)-S. Cloning efficiency in soft
      agar and tumorigenicity in nude mice was also markedly inhibited in HepG(2)-AS.
      CONCLUSIONS: Antisense gene to hTRT can significantly suppress cancer cell
      growth, partially reverse malignant phenotypes of HepG(2), which indicates that
      hTRT may be a new target gene for antisense gene therapy of liver cancer.

PMID- 11983123
TI  - [Expression and clinical significance of MAGE-4 gene in human hepatocellular
      carcinoma].
AB  - OBJECTIVE: To explore the possibility of MAGE-4 gene encoding protein used as a
      target for immunotherapy in HCC patients. METHODS: The expression of MAGE-4 gene
      in tumor tissues and tumor adjacent non-HCC liver tissues was examined by the RT
      PCR method. The relationship between positive expression rate of MAGE-4 gene and
      other clinical and lab data including AFP, AFU, anti-HCV, HBsAg, AFP mRNA, and
      the diameter of the tumors in HCC patients was also determined. RESULTS: The
      positive expression rate of MAGE-4 gene was significantly higher in the tumor
      than in tumor surrounding tissues (38.7% vs 0%, P<0.01), while the positive
      expression rate of MAGE-4 gene had no relationship with the clinical and lab data
      (P>0.05). CONCLUSIONS: The high frequency of MAGE-4 gene expression in HCC
      suggests the possibility of MAGE-4 gene encoding protein as a target for
      immunotherapy in HCC patients, but the expression has no relationship with the
      tumor metastasis and the recurrence of HCC.

PMID- 11983124
TI  - [Ursodeoxycholic acid promotes liver regeneration after partial hepatectomy in
      bile duct obstructive rats].
AB  - OBJECTIVE: To investigate the effect of ursodeoxycholic acid (UDCA) on liver
      regeneration after 70% partial hepatectomy (PH) in bile duct obstructive (BDO)
      rats. METHODS: Wistar rats were randomly divided into N-PH group in which normal
      rats were operated with 70% PH, BDO-PH group in which 70% PH were operated after
      two week's BDO, and BDO-PH UDCA or sterile saline treatment group in which UDCA
      (15mg kg(-1) d(-1)) or saline was administrated during BDO and after 70% PH. The
      hepatic pathological changes were observed. BrdU labeling of hepatocytes, the
      mRNA expression of intrahepatic hepatocyte growth factor (HGF) and its receptor
      (Met gene) after 70% PH were measured by immunohistochemical analysis and RT-PCR,
      respectively. RESULTS: Improvements of hepatic function and pathological changes
      were induced by UDCA administration after BDO. The expression of hepatic HGF/Met
      mRNA after 70% PH in BDO-PH UDCA treatment group rats was significantly increased
      compared with N-PH group rats (P<0.05), BrdU peak labelling of hepatocytes
      (59.39% +/- 10.82%) in BDO-PH UDCA treatment group rats was significantly higher
      than that (36.22% +/- 8.37%) in BDO-PH group rats (t=4.149, P<0.01) and without
      significance compared with N-PH group rats (68.64% +/- 11.26%, t=1.451, P >0.05).
      CONCLUSIONS: UDCA promotes liver regeneration after 70% PH in BDO rats by
      remission of hepatic pathological changes and elevating hepatic mRNA expression
      of HGF and Met.

PMID- 11983125
TI  - [Construction of eukaryotic expression plasmids inserting HBsAg gene and DNA
      immunization responses to HBsAg in mice].
AB  - OBJECTIVE: To study the HBsAg transient expression in HepG2 or COS-7 cells with
      eukaryotic expression plasmids inserting HBsAg gene (pCI-S and pcDNA3.1-S) and
      the efficacy of naked DNA immunization in mice. METHODS: Firstly, the recombinant
      plasmids of pCI-S and pcDNA3.1-S were constructed by the cloning technique and
      the accuracy of these constructs was confirmed by restriction enzyme digestion
      and DNA sequencing. Secondly, plasmids of pCI-S and pcDNA3.1-S were transferred
      into HepG2 and COS-7 cells, respectively by means of cationic liposome. HBsAg
      transient expression was assayed by ELISA in cell culture supernatants and cell
      lysates. Thirdly, plasmids were injected into quadriceps muscles of BALB/C mice
      and serum samples were obtained from individual immunized or control mice 4 weeks
      after injection and boost injection, respectively. Anti-HBs were assayed in mice
      sera by ELISA. HBsAg-specific CTL responses of spleen cells from immunized mice
      were tested by the LDH method. RESULTS: Plasmids of pCI-S and pcDNA3.1-S allowed
      HBsAg transient expression in cell culture supernatants and cell lysates of HepG2
      or COS-7 cells. Intramuscular immunization of BALB/C mice with plasmids of pCI-S
      or pcDNA3.1-S elicited the antibody and cytotoxic T lymphocyte responses to
      HBsAg. CONCLUSIONS: The vectors used in this study are effective to induce prime
      antibody and HBsAg-specific-cytotoxic T lymphocyte responses to HBsAg in mice
      after intramuscular immunization.

PMID- 11983126
TI  - [Preparation of human single chain Fv antibody specifically against hepatitis C
      virus E2 antigen].
AB  - OBJECTIVE: To identify human single chain Fv antibody (ScFv) against hepatitis C
      viral E2 antigen and its value clinically. METHODS: The recombinant phages were
      panned by E2 antigen which was coated in a microtiter plate. After five rounds of
      biopanning, 56 phage clones were identified specific to E2 antigen. The affinity
      and specificity of ScFv were evaluated by ELISA and immunohistochemistry,
      respectively. RESULTS: The data of E2-ScFv DNA digestion and DNA sequencing
      showed that the ScFv gene was composed of 750bp. ELISA and immunohistochemistry
      demonstrated that the human single chain Fv antibody against HCV E2 antigen had a
      specific combination character with hepatitis C virus E2 antigen. CONCLUSIONS:
      ScFv, having a sutestantial affinity and specificity and being easy to prepare,
      is valuable in the detection of HCV E2 antigen.

PMID- 11983127
TI  - [Anti-HBV effect of sulfated polysaccharides from seaweed both in vitro and in
      vivo].

PMID- 11983128
TI  - [Expression and identification of specific autoantigens in autoimmune hepatitis].
AB  - OBJECTIVE: To express and identify soluble liver antigen (SLA) and cytochrome P
      450 (CYP 2D6). METHODS: SLA cDNA and CYP 2D6 cDNA were obtained from human liver
      tissue poly (A)+RNA by RT-PCR. The cDNAs were inserted into fusion expression
      vector PQE-30 site of BamH I and Hind III. SLA and CYP 2D6 were identified by the
      SDS-PAGE and Western blot. RESULTS: SDS-PAGE analysis showed that there was a
      very strong stained band at about 47 kd and 50 kd, respectively. The products
      could specifically band to anti-SLA or anti-CYP 2D6 autoantibodies. CONCLUSIONS:
      The clone and expression of SLA and CYP 2D6 provide useful substances for the
      diagnosis and research of pathogenesis on autoimmune hepatitis.

PMID- 11983129
TI  - [Effect of IL-12 on IFN-gamma and IL-10 produced by peripheral blood mononuclear
      cells in patients with chronic hepatitis B virus infection during IFN-alpha
      treatment].
AB  - OBJECTIVE: To investigate the effect of IL-12 on IFN-gamma and IL-10 production
      of peripheral blood mononuclear cells (PBMC) in chronic hepatitis B virus
      infection patients during IFN-alpha treatment. METHODS: Before and after IFN
      alpha treatment of 3 months and 6 months, PBMC of 20 patients with chronic
      hepatitis B virus infection were collected and cultured in vitro in the culture
      fluid containing PHA (100 microg/ml), HBcAg (1 microg/ml), or HBeAg (1 microg/ml)
      for 48 h under the condition of the presence or absence of IL-12 (10 ng/ml). Then
      the levels of IFN-gamma and IL-10 were determined by ELISA. RESULTS: There were
      12 responders and 8 nonresponders to IFN-alpha treatment. In the responders, the
      enhancing effect of IL-12 on IFN-gamma production was significantly greater after
      IFN-alpha treatment than before the treatment. The production of IL-10 was
      suppressed in the presence of IL-12 after 3 months and 6 months of IFN-alpha
      treatment. In the same treatment time, the level of IFN-gamma in the presence of
      IL-12 was significantly higher than that in the absence of IL-12. To the
      nonresponders, the enhancing effect of IL-12 on IFN-gamma production was also
      significantly increased after IFN-alpha treatment. Moreover, in the same
      treatment time, the level of IFN-gamma in the presence of IL-12 was significantly
      higher than that in the absence of IL-12. CONCLUSIONS: The enhancing effect of IL
      12 on IFN-gamma production of PBMC in patients with chronic hepatitis B virus
      infection is increased during IFN-alpha treatment. IFN-alpha and IL-12 may
      enhance the efficacy for the treatment of chronic hepatitis B virus infection.

PMID- 11983130
TI  - [Construction of hepatocyte growth factor expression vector and detection of
      expression in human hepatocytes].

PMID- 11983131
TI  - [The value of gamma-glutamyltransferase in the diagnosis of chronic hepatitis B].
AB  - OBJECTIVE: To explore the change of serum gamma-glutamyltransferase (GGT) and its
      diagnosis value in chronic hepatitis B (CHB) patients with different degrees of
      liver damage. METHODS: Alanine-aminotransferase (ALT), aspartate-aminotransferase
      (AST) and GGT were measured in 221 CHB patients. Liver biopsy was conducted
      simultaneously to determine the inflammation grade and fibrosis stage of the
      liver tissues. RESULTS: The rate of normal GGT in pathologically diagnosed mild
      and severe CHB patients was 90.4% and 12.3%, respectively (P<0.01). Increased
      level of GGT was parallel to the degree of liver pathological change (P<0.01). In
      active CHB patients, GGT rose with the ALT increase with a positive linear
      correlation between them (r=0.464, P<0.001). In pathologically diagnosed mild CHB
      patients, GGT had a tendency of rapidly declining to normal levels with ALT. In
      moderate CHB patients, GGT fluctuated at a relatively high level, and in severe
      CHB patients GGT exhibited a deviation from GGT. CONCLUSIONS: GGT is conducive to
      improve the coincident rate between the clinical and pathological diagnosis of
      CHB.

PMID- 11983132
TI  - [Influence of interferon alpha on the variation of Tc and Ts cells in the
      peripheral blood of patients with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the influence of interferon-alpha on the variation of
      cytotoxic T lymphocytes (Tc) and suppressor T lymphocytes (Ts) in the peripheral
      blood of 32 patients with chronic hepatitis B, and to analyse the relationship
      between the efficacy of interferon-alpha and the variation of Tc and Ts cells.
      METHODS: The peripheral blood Tc and Ts cells were detected by the double
      staining immunocytochemistry technique. RESULTS: At the end of the treatment with
      interferon-alpha, there were 9 complete responders (CR), 12 partial responders
      (PR) and 11 non-responders (NR). Tc cells significantly increased and Ts cells
      markedly decreased in CR or PR group compared with the healthy control group.
      There was no significant difference in the level of Tc and Ts cells between CR
      and PR groups, and no significant difference in the level of Tc cells in NR, CR
      and PR groups, The Ts cells was significantly higher in NR group than in CR or PR
      group. CONCLUSIONS: The treatment of interferon-alpha can result in the change of
      Tc and Ts cells in patients with chronic hepatitis B. The variation of Ts cells
      may play an important role in the efficacy of interferon-alpha against hepatitis
      B virus.

PMID- 11983133
TI  - [Determination and the significance of three types of GGT mRNA in human liver
      tissues].
AB  - OBJECTIVE: To explore the relationship between the alteration in GGT mRNA
      expression and the development of HCC. METHODS: Three GGT mRNA types (F, H, and
      P) in normal liver tissues, diseased liver tissues without HCC, cancerous and
      noncancerous tissues from livers with HCC, and noncancerous tissues from livers
      with metastatic tumor were tested by RT-PCR. RESULTS: In normal livers, the main
      type of GGT mRNA was type F. In liver diseases but not HCC, the distribution of
      the type GGT mRNA was nearly the same as in normal livers. The prevalence of type
      H was significantly higher in both cancerous and noncancerous tissues of livers
      with HCC than in livers without HCC (P<0.05). The prevalence of type F in
      cancerous tissues was significantly lower than that in livers without HCC
      (P<0.05). CONCLUSIONS: The GGT mRNA expression in the human liver will shift from
      type F to type H during the development of HCC. The fragment analysis of GGT
      genes may be a sensitive assay to detect hepatic cell canceration.

PMID- 11983134
TI  - [Relationship between plasma carbon monoxide and blood-brain barrier permeability
      in cirrhotic rats].
AB  - OBJECTIVE: To explore the relationship between plasma levels of carbon monoxide
      and blood-brain permeability in cirrhotic rats. METHODS: We measured mean
      arterial pressure (MAP), heart rate, plasma levels of carbon monoxide and amount
      of Evans blue in the brain tissue taken as the index of blood-brain permeability
      in cirrhotic rats (n=10) and controls (n=10). RESULTS: Cirrhotic rats showed
      significant increases in plasma carbon monoxide and amount of Evans blue in brain
      tissue compared with controls [(18.37 +/- 1.79) micromol/L,(18.52 +.- 1.39) ng/mg
      vs (10.27 +/- 1.21) micromol/L, (15.08 +/- 1.06) ng/mg; P< 0.01]. Carbon monoxide
      levels in cirrhotic rats correlated positively with blood-brain barrier
      permeability and inversely with MAP (r=0.72, P< 0.01; r= -0.67, P< 0.05).
      CONCLUSIONS: Carbon monoxide, involving in the occurrence of hypotension and the
      increase of blood-brain barrier permeability, may play a role in the development
      of hepatic encephalopathy.

PMID- 11983135
TI  - [Diagnostic value of ultrasonic examination in patients with different stages of
      liver fibrosis].
AB  - OBJECTIVE: To discuss the diagnostic value of ultrasonic examination in patients
      with early liver cirrhosis and the relation with different stages of liver
      fibrosis. METHODS: In the series, 263 patients with chronic hepatitis B were
      under taken liver biopsy and ultrasonic examination of type B for determination
      of liver cirrhosis images, width of the main portal vein and the splenic vein,
      tumefaction of the spleen. Data were analysed statistically. RESULTS: Sixties of
      263 patients were diagnosed as early liver cirrhosis. The diagnostic sensitivity,
      specificity, misdiagnostic rate, missed diagnostic rate, and Jonden's index of
      ultrasonic examination for early liver cirrhosis were 52.5%, 88.3%, 11.7%, 47.5%,
      and 0.508, respectively. The width of the main portal vein with liver fibrosis of
      S1, S2, S3, and S4 were 10.93 mm +/- 1.25 mm, 11.35 mm +/- 1.06 mm,11.29 mm +/-
      1.52 mm, and 11.4 8mm +/- 1.25 mm, respectively with statistic difference between
      S4 and S1 (P=0.03). The width of the spleen vein of S1, S2, S3, and S4 were 6.518
      mm +/- 2.033 mm, 7.190 mm +/- 1.569 mm, 7.444 mm +/- 1.805 mm and 8.406 mm +/-
      2.227 mm, respectively with statistic difference between S4 and S2 (P=0.035). The
      incidence of tumefaction of the spleen was increased with the degree of liver
      fibrosis. CONCLUSIONS: The diagnostic sensitivity of ultrasonic examination for
      early liver cirrhosis is low. The width of the main portal vein, the spleen vein
      and the incidence of tumefaction of the spleen are related with the degree of
      liver fibrosis. The regeneration node of liver cirrhosis may contribute to the
      development of portal hypertension.

PMID- 11983136
TI  - [Correlative study between portal vein pressure and portal hemodynamics in
      patients with portal hypertension].
AB  - OBJECTIVE: To explore the characteristics of the portal vein hemodynamics and the
      correlation with the portal vein pressure. METHODS: There were 41 cases of
      hepatic cirrhosis complicating portal hypertension. The liver function was graded
      Child-Pugh A+B in 31 cases and Child-Pugh C in 10 cases. The inner-diameter and
      blood stream speed of the portal vein (PV), the spleen vein (SV) and the superior
      mesentery vein (SMV) were measured by the color Doppler ultrasonography. The
      vascular acreage and blood flow volume were calculated. The portal vein pressure
      was directly measured during the operation. Thirty-two healthy people and 26
      patients with chronic hepatitis B (CHB) served as controls in this study.
      RESULTS: The inner-diameter of the three veins was obviously wider and the blood
      flow speed was slower in two portal hypertension groups than in CHB and normal
      groups (P<0.01). In Child C group, the speed was the slowest. The speed of SV and
      SMV in two hypertension groups did not show any significant difference (P>0.05).
      In Child A+B group, the blood flow volume of the three veins was larger than that
      in normal and CHB groups (P<0.01 or P<0.05). The volume of PV was less in Child C
      group than Child A+B group (P<0.01), but the volume of SV and SMV was not
      obviously different (P>0.05). In Child A+B group, the portal vein pressure (Ppv)
      had a close correlation with the portal vein width, blood flow quantitation
      (Qpv), and blood stream volume (Qsv) of the spleen vein. CONCLUSIONS: The Qpv in
      Child A+B grade can be measured by the color Doppler ultrasonography technique,
      and the portal vein pressure can be monitored easily by the equation of
      Ppv=1.8951+0.0011Qpv.

PMID- 11983137
TI  - [The value of spiral multi phase scans in the diagnosis of the inflammatory
      pseudotumor of liver].

PMID- 11983138
TI  - [Expression of HBsAg in the multi-tissues of died fetus delivered by parturients
      with hepatitis B].

PMID- 11983139
TI  - [CT, MR and DSA imaging in the follow-up of patients with hepatocellular
      carcinoma well filled with lipiodol after transcatheter arterial
      chemoembolization].

PMID- 11983140
TI  - [Analysis of 10 patients with viral hepatitis concomitant acute pancreatitis].

PMID- 11983141
TI  - [Effects of neuropeptide Y on hemodynamics and sodium secretion in cirrhotic rats
      with portal hypertension].

PMID- 11983142
TI  - [Amelioration of carbon tetrachloride-induced hepatic fibrosis in rats by
      treatment with salvia miltiorrhiza and taurine].

PMID- 11983143
TI  - [Establishment of modified model of Vx-2 carcinoma in rabbit liver and DSA
      imagining features of the tumor].

PMID- 11983144
TI  - [Relationship between fatty liver and atherosclerosis, and coronary
      atherosclerotic heart disease].

PMID- 11983145
TI  - [Effects of oxidative stress on hepatic stellate cells activation].

PMID- 11983146
TI  - [Cirrhotic myocardiopathy].

PMID- 11983147
TI  - [The prospect on the technique of test for blood donor infected with hepatitis C
      virus during the infectious window period].

PMID- 11983148
TI  - An invitation to T and more: notch signaling in lymphopoiesis.
AB  - Cell fate decisions in metazoans are regulated by Notch signals. During lymphoid
      development, Notch influences a series of cell fate decisions involving
      multipotent progenitors. This review focuses on current views and lingering
      uncertainties about Notch function in lymphoid cells.

PMID- 11983149
TI  - WNT signaling and lymphocyte development.
AB  - Developmental studies in model organisms have revealed that cell fate decisions
      are governed by only a handful of highly conserved signal transduction cascades.
      Recent data indicate that at least two of these, the Wnt and the Notch cascades,
      have been recruited by the vertebrate immune system to control early
      lymphopoiesis.

PMID- 11983150
TI  - Genetic control of MHC class II expression.
AB  - The presentation of peptides to T cells by MHC class II molecules is of critical
      importance in specific recognition by the immune system. Expression of class II
      molecules is exquisitely controlled at the transcriptional level. A large set of
      proteins interact with the promoters of class II genes. The most important of
      these is CIITA, a master controller that orchestrates expression but does not
      bind directly to the promoter. The transcriptosome complex formed at class II
      promoters is a model for induction of gene expression.

PMID- 11983151
TI  - Somatic hypermutation of immunoglobulin genes: merging mechanisms for genetic
      diversity.
AB  - Somatic hypermutation is critical for the generation of high-affinity antibodies
      and effective immune responses, but its molecular mechanism remains poorly
      understood. Recent studies have identified DNA strand lesions associated with the
      hypermutation process and suggested the involvement of specific repair molecules
      and pathways. Particularly exciting has been the discovery of a putative RNA
      editing enzyme, the activation-induced cytidine deaminase (AID), that is required
      for all immunoglobulin gene-specific modification reactions (somatic
      hypermutation, class switch recombination, and gene conversion). Parallels
      between these three reactions are considered in light of recent advances.

PMID- 11983152
TI  - The mechanism and regulation of chromosomal V(D)J recombination.
AB  - V(D)J recombination is of fundamental importance to the generation of diverse
      antigen receptor repertoires. We review our current understanding of the V(D)J
      recombination reaction and how it is regulated during lymphocyte development. We
      also discuss how defects in the mechanism or regulation of V(D)J recombination
      can lead to human disease.

PMID- 11983153
TI  - Nuclear hormone receptors in T lymphocytes.
AB  - Among the numerous steroid and orphan nuclear receptors encoded within mammalian
      genomes, several are involved in regulating immune system functions. We review
      here recent studies on the glucocorticoid receptor and the orphan receptors Nur77
      and RORgamma. These molecules play key roles in the development and the effector
      functions of T lymphocytes.

PMID- 11983154
TI  - NFAT signaling: choreographing the social lives of cells.
AB  - Calcium signaling activates the phosphatase calcineurin and induces movement of
      NFATc proteins into the nucleus, where they cooperate with other proteins to form
      complexes on DNA. Nuclear import is opposed by kinases such as GSK3, thereby
      rendering transcription continuously responsive to receptor occupancy.
      Disruptions of the genes involved in NFAT signaling are implicating this pathway
      as a regulator of developmental cell-cell interactions.

PMID- 11983155
TI  - Missing pieces in the NF-kappaB puzzle.
AB  - The regulation of the transcription factor NF-kappaB activity occurs at several
      levels including controlled cytoplasmic-nuclear shuttling and modulation of its
      transcriptional activity. A critical component in NF-kappaB regulation is the
      IkappaB kinase (IKK) complex. This review is focused on recent progress as well
      as unanswered questions regarding the regulation and function of NF-kappaB and
      IKK.

PMID- 11983156
TI  - Pathways of apoptosis in lymphocyte development, homeostasis, and disease.
AB  - Apoptosis plays a critical role in lymphocyte development and homeostasis.
      Enhanced lymphocyte apoptosis can cause immunodeficiency through cell loss.
      Conversely, inhibition of apoptosis can lead to the development of autoimmunity
      or lymphoma. Two major pathways contribute to the regulation of lymphocyte cell
      death, death-by-neglect and death-by-instruction.

PMID- 11983157
TI  - Transcription: tantalizing times for T cells.
AB  - The T helper lymphocyte is responsible for orchestrating an appropriate immune
      response to pathogens. To do so, it has evolved into two specialized subsets that
      direct type 1 and type 2 immunity. Here, we discuss the genetic programs that
      control lineage commitment of progenitor T helper cells along each of these
      pathways.

PMID- 11983158
TI  - Cytokine signaling in 2002: new surprises in the Jak/Stat pathway.
AB  - The importance of Jak-Stat pathway signaling in regulating cytokine-dependent
      gene expression and cellular development/survival is well established.
      Nevertheless, advances continue to be made in defining Jak-Stat pathway effects
      on different cellular processes and in different organisms. This review focuses
      on recent advances in the field and highlights some of the most active areas of
      Jak-Stat pathway research.

PMID- 11983159
TI  - Fat targets for insulin signaling.
AB  - Adipose cells control flux of fatty acids to peripheral tissues by storing and
      hydrolyzing triglyceride under hormonal control. New data reveal that insulin may
      regulate this process in part by promoting membrane trafficking of intracellular
      fatty acid transporters FATP1 and FATP4 to the plasma membrane.

PMID- 11983160
TI  - Linking activators and basals in transcription: it is all in one family.
AB  - Analysis of nuclear hormone receptor function in cells derived from xeroderma
      pigmentosum patients reveals novel links between DNA repair and transcription and
      points to novel mechanisms of regulating transcriptional regulators.

PMID- 11983161
TI  - RfaH, a bacterial transcription antiterminator.
AB  - The bacterial transcription antiterminator RfaH has been shown to act, in a
      purified biochemical system, by binding both RNA polymerase and the nontemplate
      strand of DNA at the regulatory site ops.

PMID- 11983162
TI  - Sex and the single (double-strand) break.
AB  - It has been known for some time that DNA double-strand breaks (DSBs) initiate
      homologous recombination during meiosis. Two recent studies show that the fate of
      a single DSB in yeast is strongly influenced by the presence of other breaks in
      the genome, hinting that cell-wide or chromosome-regional mechanisms control the
      outcome of DSB repair.

PMID- 11983163
TI  - Only connect: linking meiotic DNA replication to chromosome dynamics.
AB  - The process of meiosis reduces a diploid cell to four haploid gametes and is
      accompanied by extensive recombination. Thus, chromosome dynamics in meiosis are
      significantly different than in mitotic cells. This review analyzes unique
      features of meiotic DNA replication and describes how it affects subsequent
      recombination and chromosome segregation.

PMID- 11983164
TI  - Sulfur sparing in the yeast proteome in response to sulfur demand.
AB  - Genome-wide studies have recently revealed the unexpected complexity of the
      genetic response to apparently simple physiological changes. Here, we show that
      when yeast cells are exposed to Cd(2+), most of the sulfur assimilated by the
      cells is converted into glutathione, a thiol-metabolite essential for
      detoxification. Cells adapt to this vital metabolite requirement by modifying
      globally their proteome to reduce the production of abundant sulfur-rich
      proteins. In particular, some abundant glycolytic enzymes are replaced by sulfur
      depleted isozymes. This global change in protein expression allows an overall
      sulfur amino acid saving of 30%. This proteomic adaptation is essentially
      regulated at the mRNA level. The main transcriptional activator of the sulfate
      assimilation pathway, Met4p, plays an essential role in this sulfur-sparing
      response.

PMID- 11983165
TI  - EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP
      BL phosphatase.
AB  - Ephrins are cell surface-associated ligands for Eph receptors and are important
      regulators of morphogenic processes such as axon guidance and angiogenesis.
      Transmembrane ephrinB ligands act as "receptor-like" signaling molecules, in part
      mediated by tyrosine phosphorylation and by engagement with PDZ domain proteins.
      However, the underlying cell biology and signaling mechanisms are poorly
      understood. Here we show that Src family kinases (SFKs) are positive regulators
      of ephrinB phosphorylation and phosphotyrosine-mediated reverse signaling. EphB
      receptor engagement of ephrinB causes rapid recruitment of SFKs to ephrinB
      expression domains and transient SFK activation. With delayed kinetics, ephrinB
      ligands recruit the cytoplasmic PDZ domain containing protein tyrosine
      phosphatase PTP-BL and are dephosphorylated. Our data suggest the presence of a
      switch mechanism that allows a shift from phosphotyrosine/SFK-dependent signaling
      to PDZ-dependent signaling.

PMID- 11983166
TI  - Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated
      Ca(2+) influx by interaction with a site in the C terminus of TrpC1.
AB  - The mechanism involved in [Ca(2+)](i)-dependent feedback inhibition of store
      operated Ca(2+) entry (SOCE) is not yet known. Expression of Ca(2+)-insensitive
      calmodulin (Mut-CaM) but not wild-type CaM increased SOCE and decreased its
      Ca(2+)-dependent inactivation. Expression of TrpC1 lacking C terminus aa 664-793
      (TrpC1DeltaC) also attenuated Ca(2+)-dependent inactivation of SOCE. CaM
      interacted with endogenous and expressed TrpC1 and with GST-TrpC1 C terminus but
      not with TrpC1DeltaC. Two CaM binding domains, aa 715-749 and aa 758-793, were
      identified. Expression of TrpC1Delta758-793 but not TrpC1Delta715-749 mimicked
      the effects of TrpC1DeltaC and Mut-CaM on SOCE. These data demonstrate that CaM
      mediates Ca(2+)-dependent feedback inhibition of SOCE via binding to a domain in
      the C terminus of TrpC1. These findings reveal an integral role for TrpC1 in the
      regulation of SOCE.

PMID- 11983167
TI  - Defining a pathway of communication from the C-terminal peptide binding domain to
      the N-terminal ATPase domain in a AAA protein.
AB  - AAA proteins remodel other proteins to affect a multitude of biological
      processes. Their power to remodel substrates must lie in their capacity to couple
      substrate binding to conformational changes via cycles of nucleotide binding and
      hydrolysis, but these relationships have not yet been deciphered for any member.
      We report that when one AAA protein, Hsp104, engages polypeptide at the C
      terminal peptide-binding region, the ATPase cycle of the C-terminal nucleotide
      binding domain (NBD2) drives a conformational change in the middle region. This,
      in turn, drives ATP hydrolysis in the N-terminal ATPase domain (NBD1). This
      interdomain communication pathway can be blocked by mutation in the middle region
      or bypassed by antibodies that bind there, demonstrating the crucial role this
      region plays in transducing signals from one end of the molecule to the other.

PMID- 11983168
TI  - Cyclin G recruits PP2A to dephosphorylate Mdm2.
AB  - The function of cyclin G, a commonly induced p53 target, has remained elusive. We
      show that cyclin G forms a quaternary complex in vivo and in vitro with
      enzymatically active phosphatase 2A (PP2A) holoenzymes containing B' subunits.
      Interestingly, cyclin G also binds in vivo and in vitro to Mdm2 and markedly
      stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with
      these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at
      T216 and markedly higher levels of p53 protein when compared to wild-type cells.
      Cyclin G expression also results in reduced phosphorylation of human Hdm2 at
      S166. Thus, our data suggest that cyclin G recruits PP2A in order to modulate the
      phosphorylation of Mdm2 and thereby to regulate both Mdm2 and p53.

PMID- 11983169
TI  - Molecular architecture of SMC proteins and the yeast cohesin complex.
AB  - Sister chromatids are held together by the multisubunit cohesin complex, which
      contains two SMC (Smc1 and Smc3) and two non-SMC (Scc1 and Scc3) proteins. The
      crystal structure of a bacterial SMC "hinge" region along with EM studies and
      biochemical experiments on yeast Smc1 and Smc3 proteins show that SMC protamers
      fold up individually into rod-shaped molecules. A 45 nm long intramolecular
      coiled coil separates the hinge region from the ATPase-containing "head" domain.
      Smc1 and Smc3 bind to each other via heterotypic interactions between their
      hinges to form a V-shaped heterodimer. The two heads of the V-shaped dimer are
      connected by different ends of the cleavable Scc1 subunit. Cohesin therefore
      forms a large proteinaceous loop within which sister chromatids might be
      entrapped after DNA replication.

PMID- 11983170
TI  - Visualization of interactions among bZIP and Rel family proteins in living cells
      using bimolecular fluorescence complementation.
AB  - Networks of protein interactions coordinate cellular functions. We describe a
      bimolecular fluorescence complementation (BiFC) assay for determination of the
      locations of protein interactions in living cells. This approach is based on
      complementation between two nonfluorescent fragments of the yellow fluorescent
      protein (YFP) when they are brought together by interactions between proteins
      fused to each fragment. BiFC analysis was used to investigate interactions among
      bZIP and Rel family transcription factors. Regions outside the bZIP domains
      determined the locations of bZIP protein interactions. The subcellular sites of
      protein interactions were regulated by signaling. Cross-family interactions
      between bZIP and Rel proteins affected their subcellular localization and
      modulated transcription activation. These results attest to the general
      applicability of the BiFC assay for studies of protein interactions.

PMID- 11983171
TI  - Exchange of RNA polymerase II initiation and elongation factors during gene
      expression in vivo.
AB  - We have systematically explored the in vivo occupancy of promoters and open
      reading frames by components of the RNA polymerase II transcription initiation
      and elongation apparatuses in yeast. RNA polymerase II, Mediator, and the general
      transcription factors (GTFs) were recruited to all promoters tested upon gene
      activation. RNA polymerase II, TFIIS, Spt5, and, unexpectedly, the Paf1/Cdc73
      complex, were found associated with open reading frames. The presence of the
      Paf1/Cdc73 complex on ORFs in vivo suggests a novel function for this complex in
      elongation. Elongator was not detected under any conditions tested, and further
      analysis revealed that the majority of elongator is cytoplasmic. These results
      suggest a revised model for transcription initiation and elongation apparatuses
      in living cells.

PMID- 11983172
TI  - Selective requirements for histone H3 and H4 N termini in p300-dependent
      transcriptional activation from chromatin.
AB  - The N-terminal tails of the core histones play important roles in transcriptional
      regulation, but their mechanism(s) of action are poorly understood. Here, pure
      chromatin templates assembled with varied combinations of recombinant wild-type
      and mutant core histones have been employed to ascertain the role of individual
      histone tails, both in overall acetylation patterns and in transcription. In
      vitro assays show an indispensable role for H3 and H4 tails, especially major
      lysine substrates, in p300-dependent transcriptional activation, as well as
      activator-targeted acetylation of promoter-proximal histone tails by p300. These
      results indicate, first, that constraints to transcription are imposed by
      nucleosomal histone components other than histone N-terminal tails and, second,
      that the histone N-terminal tails have selective roles, which can be modulated by
      targeted acetylation, in transcriptional activation by p300.

PMID- 11983173
TI  - Activator-specific recruitment of TFIID and regulation of ribosomal protein genes
      in yeast.
AB  - In yeast, TFIID strongly associates with nearly all ribosomal protein (RP)
      promoters, but a TAF-independent form of TBP preferentially associates with other
      active promoters. RP promoters are regulated in response to growth stimuli, in
      most cases by a Rap1-containing activator. This Rap1-dependent activator is
      necessary and sufficient for TFIID recruitment, whereas other activators do not
      efficiently recruit TFIID. TAFs are recruited to RP promoters even when TBP and
      other general transcription factors are not associated, suggesting that TFIID
      recruitment involves a direct activator-TAF interaction. Most RP promoters lack
      canonical TATA elements, and they are preferentially activated by the Rap1
      containing activator. These results demonstrate activator-specific recruitment of
      TFIID in vivo, and they suggest that TFIID recruitment is important for
      coordinate expression of RP genes.

PMID- 11983174
TI  - Wild-type levels of Spo11-induced DSBs are required for normal single-strand
      resection during meiosis.
AB  - We have studied the repair of a DNA-DSB created by the VMA1-derived endonuclease
      in mutants that have different levels of Spo11-DSBs: WT (sae2), few (hop1), and
      none (spo11-Y135F). In spo11-Y135F and hop1 cells, intrachromosomal repair is
      more frequent than in WT and sae2 cells. In spo11-Y135F cells there was no
      chromosome pairing or synapsis and a faster turnover of resected DNA. Compared to
      WT and sae2 cells, spo11-Y135F and hop1 cells have a greater proportion of long
      resection tracts. The data suggest that high levels of Spo11-DSBs are required
      for normal regulation of resection, even at a DSB created by another protein. WT
      control over resection could be important for directing repair to be
      interchromosomal, increasing the chance of creating interhomolog connections
      essential to meiotic segregation.

PMID- 11983175
TI  - Meiotic DNA breaks at the S. pombe recombination hot spot M26.
AB  - The ade6-M26 allele of Schizosaccharomyces pombe creates a well-defined meiotic
      recombination hot spot that requires a specific sequence, 5'-ATGACGT-3', and the
      Atf1*Pcr1 transcription factor for activity. We find that M26 stimulates the
      formation of meiosis-specific double-strand DNA breaks at multiple sites
      surrounding M26. Like hot spot activity, breakage requires the M26 heptamer,
      Pcr1, and the general recombination factor Rec12. When the M26 heptamer is moved
      to new positions within ade6, new break sites are observed spanning approximately
      0.5-2 kb around the moved heptamer. Break frequency is strongly correlated with
      recombination frequency for these alleles. The occurrence of breaks at M26
      suggests mechanistic similarities to hot spots in the distantly related yeast
      Saccharomyces cerevisiae.

PMID- 11983176
TI  - Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo.
AB  - The Lcd1p/Mec1p complex is crucial for normal S phase progression and for
      signaling DNA damage. We show that Lcd1p/Ddc2p and Mec1p in cell extracts bind to
      DNA ends. Although Lcd1p binds DNA independently of Mec1p, recruitment of Mec1p
      to DNA requires Lcd1p. DNA binding by Lcd1p is also independent of Rad9p, Rad17p,
      and Rad24p. Recombinant Lcd1p binds DNA, and this is impaired by Lcd1p mutations
      that abrogate its in vivo functions. Furthermore, Mec1p is recruited to cdc13
      induced DNA damage and HO endonuclease-induced double-strand breaks in vivo. This
      requires Lcd1p, and recruitment of Lcd1p/Mec1p to cdc13-induced damage is
      abolished by Lcd1p mutations that abrogate its in vivo functions. Recruitment of
      Lcd1p to these lesions is independent of Mec1p and Rad9p/Rad24p. Thus,
      recruitment of Mec1p to DNA lesions by Lcd1p is crucial for the DNA damage
      response.

PMID- 11983177
TI  - The V(D)J recombinase efficiently cleaves and transposes signal joints.
AB  - V(D)J recombination generates two types of products: coding joints, which
      constitute the rearranged variable regions of antigen receptor genes, and signal
      joints, which often form on immunologically irrelevant, excised circular
      molecules that are lost during cell division. It has been widely believed that
      signal joints simply convert reactive broken DNA ends into safe, inert products.
      Yet two curious in vivo observations made us question this assumption: signal
      ends are far more abundant than coding ends, and signal joints form only after
      RAG expression is downregulated. In fact, we find that signal joints are not at
      all inert; they are cleaved quite efficiently in vivo and in vitro by a nick-nick
      mechanism and form an excellent substrate for RAG-mediated transposition in
      vitro, possibly explaining how genomic stability in lymphocytes may be
      compromised.

PMID- 11983178
TI  - Inhibition of reverse transcription in vivo by elevated manganese ion
      concentration.
AB  - Mutations in PMR1, a yeast gene encoding a calcium/manganese exporter,
      dramatically decrease Ty1 retrotransposition. Ty1 cDNA is reduced in pmr1 mutant
      cells, despite normal levels of Ty1 RNA and proteins. The transposition defect
      results from Mn(2+) accumulation that inhibits reverse transcription. Cytoplasmic
      accumulation of Mn(2+) in pmr1 cells may directly affect reverse transcriptase
      (RT) activity. Trace amounts of Mn(2+) potently inhibit Ty1 RT and HIV-1 RT in
      vitro when the preferred cation, Mg(2+), is present. Both Mn(2+) and Mg(2+) alone
      activate Ty1 RT cooperatively with Hill coefficients of 2, providing kinetic
      evidence for a dual divalent cation requirement at the RT active site. We propose
      that occupancy of the B site is the major determinant of catalytic activity and
      that Mn(2+) at this site greatly reduces catalytic activity.

PMID- 11983179
TI  - Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a
      conserved methyltransferase that is localized to the nucleolus.
AB  - The m(7)G caps of most spliceosomal snRNAs and certain snoRNAs are converted
      posttranscriptionally to 2,2,7-trimethylguanosine (m(3)G) cap structures. Here,
      we show that yeast Tgs1p, an evolutionarily conserved protein carrying a
      signature of S-AdoMet methyltransferase, is essential for hypermethylation of the
      m(7)G caps of both snRNAs and snoRNAs. Deletion of the yeast TGS1 gene abolishes
      the conversion of the m(7)G to m(3)G caps and produces a cold-sensitive splicing
      defect that correlates with the retention of U1 snRNA in the nucleolus.
      Consistently, Tgs1p is also localized in the nucleolus. Our results suggest a
      trafficking pathway in which yeast snRNAs and snoRNAs cycle through the nucleolus
      to undergo m(7)G cap hypermethylation.

PMID- 11983180
TI  - A mechanism for microtubule depolymerization by KinI kinesins.
AB  - Whereas most kinesins motor along microtubules, KinI kinesins are microtubule
      depolymerizing machines. Surprisingly, we found that a KinI fragment consisting
      of only the motor core is capable of ATP-dependent depolymerization. The motor
      binds along microtubules in all nucleotide states, but in the presence of AMPPNP,
      microtubule depolymerization also occurs. Structural characterization of the
      products of AMPPNP-induced destabilization revealed a snapshot of the disassembly
      machine in action as it precisely deformed a tubulin dimer. While conventional
      kinesins use the energy of ATP binding to execute a "powerstroke," KinIs use it
      to bend the underlying protofilament. Thus, the relatively small class-specific
      differences within the KinI motor core modulate a fundamentally conserved mode of
      interaction with microtubules to produce a unique depolymerizing activity.

PMID- 11983181
TI  - A caspase-related protease regulates apoptosis in yeast.
AB  - Yeast can undergo cell death accompanied by cellular markers of apoptosis.
      However, orthologs of classical mammalian apoptosis regulators appeared to be
      missing from the yeast genome, challenging a common mechanism of yeast and
      mammalian apoptosis. Here we investigate Yor197w, a yeast protein with structural
      homology to mammalian caspases, and demonstrate caspase-like processing of the
      protein. Hydrogen peroxide treatment induces apoptosis together with a caspase
      like enzymatic activity in yeast. This response is completely abrogated after
      disruption and strongly stimulated after overexpression of Yor197w. Yor197w also
      mediates the death process within chronologically aged cultures, pointing to a
      physiological role in elimination of overaged cells. We conclude that Yor197w
      indeed functions as a bona fide caspase in yeast and propose the name Yeast
      Caspase-1 (YCA1, gene YCA1).

PMID- 11983183
TI  - Can't shake that feeling: event-related fMRI assessment of sustained amygdala
      activity in response to emotional information in depressed individuals.
AB  - BACKGROUND: Previous research suggests that depressed individuals engage in
      prolonged elaborative processing of emotional information. A computational neural
      network model of emotional information processing suggests this process involves
      sustained amygdala activity in response to processing negative features of
      information. This study examined whether brain activity in response to emotional
      stimuli was sustained in depressed individuals, even following subsequent
      distracting stimuli. METHODS: Seven depressed and 10 never-depressed individuals
      were studied using event-related functional magnetic resonance imaging during
      alternating 15-sec emotional processing (valence identification) and non
      emotional processing (Sternberg memory) trials. Amygdala regions were traced on
      high-resolution structural scans and co-registered to the functional data. The
      time course of activity in these areas during emotional and non-emotional
      processing trials was examined. RESULTS: During emotional processing trials,
      never-depressed individuals displayed amygdalar responses to all stimuli, which
      decayed within 10 sec. In contrast, depressed individuals displayed sustained
      amygdala responses to negative words that lasted throughout the following non
      emotional processing trials (25 sec later). The difference in sustained amygdala
      activity to negative and positive words was moderately related to self-reported
      rumination. CONCLUSIONS: Results suggest that depression is associated with
      sustained activity in brain areas responsible for coding emotional features.

PMID- 11983184
TI  - Enlargement of the amygdala in patients with a first episode of major depression.
AB  - BACKGROUND: The amygdala plays a crucial role in the mediation of affective
      behavior in humans and is implemented in the limbic-thalamic-cortical network
      that is supposed to modulate human mood. The aim of the present study was to
      measure the amygdala volumes in patients with a first episode of major
      depression. METHODS: Thirty inpatients with a first episode of depression were
      compared with 30 healthy volunteers matched for age, gender, handedness, and
      education by performing structural magnetic resonance imaging (MRI) measures of
      the amygdala. RESULTS: Patients showed increased amygdala volumes in both
      hemispheres as compared to healthy control subjects. No significant correlations
      were found between amygdala volumes and age, age of onset, illness duration, or
      severity of depression in the patient group. CONCLUSIONS: Enlarged amygdala
      volumes in patients with a first episode of major depression might be due to
      enhanced blood flow in the amygdala rather than to a neurodevelopmental
      structural predisposition to major depression.

PMID- 11983185
TI  - Serotonin transporter binding in patients with mood disorders: a PET study with
      [11C](+)McN5652.
AB  - BACKGROUND: Several lines of studies have suggested the involvement of serotonin
      transporter (5-HTT) in the pathophysiology of mood disorders. The aim of this
      study was to examine whether 5-HTT binding was altered in patients with mood
      disorders using positron emission tomography (PET). METHODS: Thirteen
      antidepressant-naive or -free patients with mood disorders and 21 age-matched
      healthy control subjects participated in this study. The patients consisted of 7
      with major depressive disorder (MDD) and 6 with bipolar disorder (BD). Positron
      emission tomography scans were performed using a selective ligand for 5-HTT,
      [11C](+)McN5652. The uptake was quantified in the thalamus and midbrain by
      graphical method with reference tissue, and binding potential (BP) was used for
      the index of 5-HTT binding. RESULTS: Binding potential in the thalamus was
      significantly increased in patients with mood disorders as compared to control
      subjects, whereas BP in the midbrain did not differ between the groups. Subgroup
      comparison showed that MDD patients had significantly higher BP in the thalamus
      compared to control subjects. Binding potential of the thalamus was higher by
      approximately 22% in the combined patients and 23% in MDD patients relative to
      control subjects. CONCLUSIONS: These findings may suggest the possibility of
      altered 5-HTT in patients with mood disorders. Functional abnormality in the
      thalamus may be involved in the pathophysiology of mood disorders.

PMID- 11983186
TI  - Initial conditions of serotonin transporter kinetics and genotype: influence on
      SSRI treatment trial outcome.
AB  - BACKGROUND: Fifty-one patients with major depression were classified for 5-HTT
      promoter region polymorphism and platelet 5-HTT kinetics before treatment with
      fluoxetine, and then examined for treatment outcome. METHODS: Dose was stratified
      from 1.25 mg to 40 mg per day to allow for the possibility that one genotype
      could express a lower-dose fluoxetine response. A repeated-measures analysis of
      variance of 24-item Hamilton depression change through baseline, 1-week placebo
      lead-in, and 6, 12, and 18 weeks treatment was done to test a genotype effect on
      outcome. RESULTS: Genotype had a significant effect on outcome (F = 4.7, p <.02),
      with the initial affinity constant (K(m)) (F = 11.9, p =.001), and dose (F = 6.0,
      p <.02) being significant covariates on outcome as well. The gene effect,
      however, was complex in that the 5-HTT promoter region insertion showed two
      effects: both a placebo response effect (F = 4, p <.025), and a drug dose
      response effect (r =.40, p <.01). The long allele group was more responsive to
      placebo, as well as more responsive to drug dose than was the short allele group.
      CONCLUSIONS: This is the first study to examine the antidepressant dose-response
      relationship to 5-HTT kinetics and genetics. The findings indicate that both the
      initial affinity and genotype of 5-HTT may contribute in unique ways to the
      variation in the outcome of depression treatment trials.

PMID- 11983187
TI  - Diminished chaos of heart rate time series in patients with major depression.
AB  - BACKGROUND: Depression and anxiety have been linked to serious cardiovascular
      events in patients with preexisting cardiac illness. A decrease in cardiac vagal
      function as suggested by a decrease in heart rate (HR) variability has been
      linked to sudden death. METHODS: We compared LLE and nonlinearity scores of the
      unfiltered (UF) and filtered time series (very low, low, and high frequency; VLF,
      LF and HF) of HR between patients with depression (n = 14) and healthy control
      subjects (n = 18). RESULTS: We found significantly lower LLE of the unfiltered
      series in either posture, and HF series in patients with major depression in
      supine posture (p <.002). LLE (LF/UF), which may indicate relative sympathetic
      activity was also significantly higher in supine and standing postures in
      patients (p <.05); LF/HF (LLE) was also higher in patients (p <.05) in either
      posture. CONCLUSIONS: These findings suggest that major depression is associated
      with decreased cardiac vagal function and a relative increase in sympathetic
      function, which may be related to the higher risk of cardiovascular mortality in
      this group and illustrates the usefulness of nonlinear measures of chaos such as
      LLE in addition to the commonly used spectral measures.

PMID- 11983188
TI  - Verapamil treatment for women with bipolar disorder.
AB  - BACKGROUND: Additional pharmacological treatments are needed for patients with
      bipolar disorder. We describe our experience with verapamil in an inclusive,
      sequential series of outpatient women (some pregnant) with bipolar disorder.
      METHODS: All women who were prescribed verapamil for bipolar disorder (n = 37)
      were included. We used the criterion of 50% reduction in scores on the Mania
      Rating Scale or the Hamilton Rating Scale for Depression to define response for
      women who were treated for an acute episode of bipolar hypomania/mania or
      depression, respectively. For euthymic women who chose verapamil maintenance
      treatment, we evaluated whether they met criteria for a recurrent episode during
      therapy. RESULTS: Treatment for acute episodes was initiated in 28 women. Of
      women with depression and mania, 39% and 100% responded, respectively. Seven of
      the nine patients (77%) with mixed states responded: all seven improved to
      response criterion on the mania scale, and two responded on the depression scales
      as well. Six of eight patients who received continuation therapy remained well.
      CONCLUSIONS: These data provide evidence that verapamil is effective for mania.
      The response rate for mania compares favorably to that for other mood
      stabilizers. After decades of case reports and underpowered clinical trials, we
      must definitively study verapamil for efficacy and gender specificity in bipolar
      disorder.

PMID- 11983189
TI  - Continuation phase treatment with bupropion SR effectively decreases the risk for
      relapse of depression.
AB  - BACKGROUND: This was the first controlled continuation phase study (up to 1-year
      total treatment) to evaluate the safety and efficacy of bupropion SR for
      decreasing the risk for relapse of depression in patients who responded to
      bupropion SR. METHODS: Patients with recurrent major depression were treated with
      bupropion SR 300 mg/day during an 8-week open-label phase. Responders (based on
      Clinical Global Impressions Scale for Improvement of Illness scores) entered a
      randomized, double-blind phase where they received bupropion SR 300 mg/day or
      placebo for up to 44 weeks. After randomization, relapse was defined as the point
      at which the investigator intervened by withdrawing the patient from the study to
      treat depression. RESULTS: Four hundred twenty-three patients were randomized. A
      statistically significant difference in favor of bupropion SR over placebo was
      seen in the time to treatment intervention for depression when survival curves
      were compared (log-rank test, p =.003). Statistically significant separation
      between bupropion SR and placebo began at double-blind week 12 (p <.05). Adverse
      events in bupropion SR-treated patients accounted for 9% and 4% of
      discontinuations from the open-label and double-blind phases, respectively.
      CONCLUSIONS: Bupropion SR was shown to be effective and well tolerated in
      decreasing the risk for relapse of depression for up to 44 weeks.

PMID- 11983190
TI  - Association of 5-HT(2A) receptor gene polymorphism with major affective
      disorders: the case of a subgroup of bipolar disorder with low suicide risk.
AB  - BACKGROUND: The implication of serotonin in suicide and affective disease
      explains why the 5-HT(2A) receptor gene has been proposed as a candidate gene in
      these disorders, although with conflicting results. METHODS: We analysed the
      distribution of the 5-HT(2A)-1438A/G genetic polymorphism in 192 patients with
      major affective disorder (127 bipolar disorders and 65 unipolar disorders)
      compared to 142 healthy control subjects. RESULTS: We found a higher frequency of
      the A allele in affected patients than in control subjects (p =.034), this
      difference being particularly striking for the subgroup of patients with type I
      bipolar disorder (p =.015). Patients with no personal and/or familial history of
      suicide attempts mainly accounted for the excess of the A allele in affected
      patients. CONCLUSIONS: The association detected in this study suggests that the 5
      HT(2A) receptor gene may play a role in the genetic susceptibility to bipolar
      disorder, through a specific subgroup of bipolar type I patients with lower risk
      of suicidal behavior.

PMID- 11983191
TI  - Neuroendocrine abnormalities in recreational ecstasy (MDMA) users: is it ecstasy
      or cannabis?
AB  - BACKGROUND: The purpose of this study was to investigate neuroendocrine function
      in ecstasy (3,4-methylenedioxymethamphetamine = MDMA) users and controls.
      METHODS: Prolactin response to d-fenfluramine was assessed in abstinent ecstasy
      users with concomitant use of cannabis only (n = 24, male/female 13/11) and in
      two control groups: healthy nonusers (n = 13, female) and exclusive cannabis
      users (n = 7, male). RESULTS: Prolactin response to d-fenfluramine was slightly
      blunted in female ecstasy users. Both male user samples exhibited a weak
      prolactin response to d-fenfluramine, but this was weaker in the group of
      cannabis users. Baseline prolactin and prolactin response to d-fenfluramine were
      associated with the extent of previous cannabis use. CONCLUSIONS:
      Endocrinological abnormalities of ecstasy users may be closely related to their
      coincident cannabis use. Cannabis use may be an important confound in
      endocrinological studies of ecstasy users and should be looked for more
      systematically in future studies.

PMID- 11983192
TI  - Memory protective effect of indomethacin against electroconvulsive shock-induced
      retrograde amnesia in rats.
AB  - BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to
      retard cognitive decrements in patients with Alzheimer's disease. We postulated
      that NSAIDs also may protect acute disruption of memory. METHODS: We studied the
      effect of indomethacin (4 mg/kg/day) administered daily for 19 days on retrograde
      amnesia induced by two once-daily electroconvulsive shocks in rats. RESULTS:
      Indomethacin produced statistically significant prolongation of recall latency in
      a passive avoidance task using a step-down apparatus. CONCLUSIONS: Our study
      suggests that NSAIDs may prevent memory disruption through other mechanisms apart
      from attenuating chronic inflammation. In patients receiving electroconvulsive
      therapy, as in those diagnosed with Alzheimer's disease, antiinflammatory drugs
      may hold promise in the attenuation of cognitive impairments.

PMID- 11983193
TI  - Fluoride content of alcoholic beverages.
AB  - BACKGROUND: In view of the conflicting reports of the extent and severity of
      dental caries in alcohol misusing subjects, a systematic survey of the fluoride
      content of alcoholic beverages was undertaken. RESULTS: The fluoride content of
      beverages varied widely particularly if non-UK European products were considered.
      CONCLUSIONS: Beers brewed in locations with high fluoride water levels may
      contribute significantly to the daily fluoride intake, particularly in alcohol
      misusing subjects and this may contribute to alcohol-associated bone disease.

PMID- 11983194
TI  - Prolonged, low dose alpha-tocopherol therapy counteracts intercellular cell
      adhesion molecule-1 activation.
AB  - BACKGROUND: Up-regulation of ICAM-1 at the vascular endothelial level is one of
      the most important promoters in the slow progression of a healthy vessel to an
      atherosclerotic one. The current study aimed to evaluate whether low dose of the
      antioxidant alpha-tocopherol affects the circulating soluble (s) ICAM-1 in
      healthy subjects. METHODS: Either alpha-tocopherol E (50 I.U./day) or placebo was
      randomly, double-blindly given to 39 healthy male volunteers (mean age 41.6+/-5.9
      years) over a period of 20 weeks. RESULTS: At the baseline, sICAM-1 levels were
      inversely correlated with alpha-tocopherol concentrations (r=-0.525, p<0.0001).
      Twenty weeks of alpha-tocopherol supplementation (n=20 subjects) significantly
      decreased the circulating sICAM-1 levels (from 149.2+/-18.4 to 131.5+/-17.2
      microg l(-1), p<0.004) while it increased the alpha-tocopherol concentrations
      (from 25.8+/-5.0 to 31.2+/-5.7 micromol l(-1), p<0.003). No significant changes
      in plasma sICAM-1 and alpha-tocopherol levels were observed in placebo-treated
      subjects (n=19). In actively treated subjects, changes in circulating sICAM-1
      were inversely correlated with changes in alpha-tocopherol concentrations (r=
      0.597, p=0.005). CONCLUSIONS: Plasma sICAM-1 concentrations are stable in healthy
      subjects over a period of 20 weeks while they significantly decreased with low
      dose of alpha-tocopherol. Thus, antioxidant vitamins are likely to counteract
      with endothelial changes that could potentially trigger the atherogenetic
      process.

PMID- 11983195
TI  - Effect of five triterpenoid compounds isolated from leaves of Diospyros kaki on
      stimulus-induced superoxide generation and tyrosyl phosphorylation in human
      polymorphonuclear leukocytes.
AB  - BACKGROUND: The crude drug "kaki-yo" is a traditional medicine used in Japan as a
      hypotensive drug. METHODS: The effect of five triterpenoid compounds, isolated
      from leaves of Diospyros kaki on stimulus-induced superoxide generation and
      phosphorylation of tyrosine residues of protein in human neutrophils was
      investigated. The five compounds examined were alpha-amyrin (A), uvaol (UV),
      ursolic acid (UA), 19 alpha-hydroxy ursolic acid (HU) and 19 alpha,24-dihydroxy
      ursolic acid (DHU). RESULTS: When the cells were preincubated with these
      compounds, the superoxide generation induced by N-formyl-methionyl-leucyl
      phenylalanine (fMLP) was significantly suppressed in a concentration-dependent
      manner. These compounds also suppressed the superoxide generation induced by
      arachidonic acid (AA) in high concentrations. In the case of the superoxide
      generation induced by phorbol 12-myristate 13-acetate (PMA), UA, HU and DHU
      suppressed the superoxide generation but A and UV gave no effect. When the cells
      were incubated with fMLP in UA, HU and DHU, fMLP-induced tyrosyl phosphorylation
      of 45 kDa proteins of the cells was dose-dependently suppressed in parallel to
      the suppression of fMLP-induced superoxide generation. CONCLUSIONS: Triterpenoid
      compounds suppress stimulus-induced superoxide generation and tyrosyl
      phosphorylation and may have pharmaceutical applications.

PMID- 11983196
TI  - Diagnosis of gastritis by means of a combination of serological analyses.
AB  - BACKGROUND: Gastroscopy and examination of biopsy is normally required for
      diagnosis of gastritis. This is costly and inconvenient for the patient, and
      there is a need for a simple pregastroscopic screening method to reduce the
      endoscopy workload. Our aim was to develop a serological screening test for
      gastritis. METHODS: Sera from subjects examined with gastroscopy and biopsy were
      analyzed for H,K-ATPase antibodies, Helicobacter pylori antibodies and pepsinogen
      I. The diagnoses were normal gastric mucosa (n=50), duodenal ulcer (n=53) and
      atrophic corpus gastritis, with (n=50) or without pernicious anemia (n=46).
      RESULTS: An evaluation scheme was constructed to optimize the diagnostic
      agreement between serology and gastric mucosal morphology. The sensitivity to
      detect gastritis was 98% (146/149) (95% CI 94-100%) and the specificity 84%
      (42/50) (95% CI 71-93%). Additional sera from 483 subjects from the general
      population were analyzed. There was a good agreement between serology and gastric
      mucosal morphology. CONCLUSIONS: Assays of multiple serum analytes are useful for
      the initial screening of gastritis. They are complementary to upper gastroscopy
      by identification of subjects with a normal gastric mucosa, those who qualify for
      eradication of H. pylori, and those who have developed atrophy and are at risk of
      developing malignancy and, therefore, require gastroscopic examination.

PMID- 11983197
TI  - Erythrocyte damage and leukocyte activation in ischemic stroke.
AB  - BACKGROUND: The traditional lipid risk factors can only predict some of the
      cardiovascular events. Our work has focused on new potential biological markers
      of risk, namely leukocyte activation and erythrocyte membrane damage, in ischemic
      stroke cases. METHODS: Besides the traditional lipid profile, we evaluated the
      plasma levels of elastase and lactoferrin as markers of leukocyte activation, and
      membrane band 3 protein profile and membrane bound hemoglobin as markers of
      erythrocyte damage. Total and differential leukocyte counts and erythrocyte
      counts, hematocrit and hemoglobin concentrations were also evaluated. The lipid
      study included the evaluation of triglycerides, total cholesterol, high-density
      lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc),
      apolipoprotein AI (Apo AI) and B (Apo B), and lipoprotein (a) (Lp(a)). The work
      was performed in a control group (n=29) with no history of cardiovascular events,
      presenting normal hematological and lipid values, and in a pathologic group
      (n=21) of ischemic stroke cases diagnosed by computed tomographic imaging.
      RESULTS: We found that ischemic stroke was associated with significantly higher
      values of leukocytes, which seem to be activated, as shown by significant higher
      levels of elastase and lactoferrin. This activation seems to impose erythrocyte
      damage, as suggested by a significant increase in membrane bound hemoglobin and
      by a different band 3 profile. CONCLUSIONS: Our data suggest that plasma levels
      of elastase and lactoferrin, together with levels of erythrocyte membrane bound
      hemoglobin and band 3 profile, could be used as powerful new markers of risk for
      cardiovascular events.

PMID- 11983198
TI  - Detection of serum antibodies to three different recombinant antigens of human
      herpesvirus 8 by immunoblotting: seroprevalence studies in Taiwan.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8), a gamma-herpesvirus, is associated with
      Kaposi's sarcoma (KS). A variety of assays for the diagnosis HHV-8 infection have
      been developed. However, the accuracy of current HHV-8 antibody testing is
      uncertain, mainly in patients with asymptomatic HHV-8 infection. METHODS: We
      utilized a new immunoblot assay, comprised of three recombinant HHV-8 encoded
      proteins (ORF16, ORF57, and ORF71) to determine the seroprevalence of HHV-8 in
      Taiwan. ORF16 encodes a Bcl-2 homologue and is expressed only in the lytic cycle.
      ORF57 is an immediate-early gene product and can activate gene expression by a
      post-transcriptional mechanism. ORF71 encodes a viral FLICE inhibitory protein
      and is a latently expressed protein. We collected 6 KS(+)/HIV(-) patients, 10 KS(
      )/HIV(+) individuals, 174 blood donors, and 62 non-KS cancer patients in this
      study. RESULTS: Among the different populations, ORF57 showed highest
      reactivities. The frequency of positive results for KS(+)/HIV(-), KS(-)/HIV(+),
      blood donors, and non-KS cancer patients were 83.3%, 40%, 23%, and 12.9%,
      respectively. Compared to the widely used lytic immunofluorescence assay, our
      immunoblotting assay using ORF57 showed higher reactivities among the blood
      donors. CONCLUSIONS: ORF57 is useful for the detection of HHV-8 infection,
      especially during the asymptomatic infections.

PMID- 11983199
TI  - Effects of diabetes mellitus and acute hypertension on plasma nitric oxide and
      endothelin concentrations in rats.
AB  - AIM: To examine the plasma nitrate/nitrite (NOx-two end products of the nitric
      oxide metabolism) and endothelin (ET) concentrations, and response to acute
      adrenaline induced hypertension in diabetic rats. MATERIALS AND METHODS: Four
      groups of 4-month-old rats were used: control rats (C, n=10) rats received
      adrenaline (A, 40 microg/kg i.v., n=10), rats received streptozotocin (S, 50
      mg/kg i.v., n=8), and rats received STZ and adrenaline (SA, n=9). The experiments
      were performed 4 weeks after the STZ administration. Plasma NOx, ET, glucose, and
      mean arterial blood pressure (MAP) were measured. RESULTS: Plasma ET
      concentrations were significantly increased in diabetic rats (S and SA) in
      comparison with the controls and adrenaline-only administered rats. NOx
      concentrations in diabetic groups (S and SA) were significantly decreased in
      comparison with the controls. Acute adrenaline induced hypertension in diabetes
      leads to a significant decrease of NOx concentrations in comparison with the
      controls, adrenaline-only administered and STZ-only administered rats. There was
      no difference between the MAP in diabetic and control rats. Adrenaline injection
      caused a significant increase of MAP in A and SA groups. Plasma glucose
      concentrations in diabetic rats (S and SA) were significantly increased in
      comparison with the nondiabetic groups (C and A). There was a weak but
      significant correlation between the NOx and ET concentrations in the controls,
      which probably reveal the balance between these vasoactive factors. In A, S, and
      SA groups, no significant correlation between the NOx/ET was found. CONCLUSION:
      An impairment of the NOx and ET formation could be involved in the pathogenesis
      of diabetes mellitus and especially acute hypertension and diabetes. A lack of
      correlation between the NOx and ET probably indicated that in diabetes and acute
      hypertension, a primary mechanism of compensatory nitric oxide might be lost.

PMID- 11983200
TI  - Serum tartrate-resistant acid phosphatase isoforms in rheumatoid arthritis.
AB  - OBJECTIVES: Our objective was to evaluate the significance and source of serum
      tartrate-resistant acid phosphatase (TRACP) in patients with rheumatoid arthritis
      (RA). METHODS: Thirty-five RA, 32 osteoarthritis (OA) and 16 control subjects
      were studied. Serum TRACP-5b activity and total TRACP protein were determined by
      immunoassay. TRACP isoforms were analyzed by non-denaturing polyacrylamide gel
      electrophoresis (PAGE). Serum bone alkaline phosphatase (BAP), cross-linked N
      terminal telopeptides (NTx), and C-terminal telopeptides (ICTP) of type I
      collagen were estimated as markers of bone turnover. C-reactive protein (CRP) was
      measured as a marker of chronic inflammation. Macrophages and dendritic cells
      (DC) were developed from peripheral blood monocytes. Cell lysates and culture
      supernatants were analyzed for TRACP isoforms by immunoassay and PAGE. RESULTS:
      In RA, mean TRACP-5b activity was normal, but median total TRACP protein was
      increased twofold (p<0.001). In OA, TRACP-5b activity and protein were normal. In
      RA, TRACP-5b activity correlated weakly with ICTP (r=0.56) while TRACP protein
      levels correlated weakly with NTx (r=0.43). Additionally, TRACP protein, but not
      TRACP-5b activity correlated significantly with CRP (r=0.42). Macrophage and DC
      lysates contained TRACP-5b, while tissue culture supernatants contained TRACP-5a.
      CONCLUSIONS: Increased total TRACP protein in RA sera was probably due to TRACP
      5a and not derived from osteoclasts. Rather, it could be a secreted product of
      inflammatory macrophages and DC.

PMID- 11983201
TI  - Corticosteroid therapy increases HDL-cholesterol concentrations in patients with
      active sarcoidosis and hypoalphalipoproteinemia.
AB  - BACKGROUND: We have previously reported that the decrease in high-density
      lipoprotein (HDL)-cholesterol that is observed in patients with untreated
      sarcoidosis is limited to those with active disease. AIM: To determine the effect
      of corticosteroids, used in the treatment of active sarcoidosis, on the reported
      lipoprotein metabolism abnormalities. METHODS: We studied 62 patients with biopsy
      proven sarcoidosis, all of them with active disease. Sarcoidosis activity was
      evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin
      converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests.
      A total of 40 patients were not treated with prednisone and 22 patients were
      treated with prednisone. The mean daily prednisone dosage in the treated patients
      with sarcoidosis was 20 mg and the mean duration of prednisone therapy was 6
      months. Analysis of lipoprotein metabolism included: serum cholesterol, low
      density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL(2)-cholesterol,
      HDL(3)-cholesterol, apolipoprotein (apo) A-I, apo B, and triglyceride
      concentrations. RESULTS: When patients with active sarcoidosis not treated with
      prednisone were compared to those treated with prednisone, the former had
      significantly lower HDL-cholesterol (1.17+/-0.36 vs. 1.42+/-0.42 mmol/l; P=0.01)
      and HDL(2)-cholesterol (0.37+/-0.18 vs. 0.53+/-0.25 mmol/l; P=0.009) levels.
      Multiple regression analysis demonstrated that the HDL-cholesterol (P=0.004),
      HDL(2)-cholesterol (P=0.002), HDL(3)-cholesterol (P=0.02), and apo A-I (P=0.02)
      levels were the variables independently and significantly associated with steroid
      therapy. CONCLUSIONS: Corticosteroid therapy, used in the treatment of active
      sarcoidosis, increased HDL-cholesterol levels to those seen in inactive disease.
      These changes are manifestations of reducing disease activity.

PMID- 11983202
TI  - Soluble tumor necrosis factor receptor levels identify a subgroup of heart
      failure patients with increased cardiomyocyte apoptosis.
AB  - BACKGROUND: We studied whether the presence of cardiomyocyte apoptosis (CA) in
      explanted failing hearts is related to previous exposure to the proinflammatory
      cytokine tumor necrosis factor alpha (TNF-alpha). METHODS: Serum levels of TNF
      alpha and its soluble type two receptors (sTNFRII) were measured with ELISAs in
      15 cardiac transplant recipients. CA was quantified with TUNEL assay in the
      explanted failing hearts and autopsy samples from six normal hearts. RESULTS: The
      number of CA was significantly higher in explanted failing hearts than in normal
      hearts (0.041% vs. 0.007%, p<0.01). In heart failure patients, serum TNF-alpha
      was highly variable and did not correlate with CA. In contrast, serum sTNFRII
      showed a significant correlation (Pearson's r=0.74, p=0.002) with the amount of
      CA in explanted hearts. sTNFRII level >4500 pg/ml identified seven patients with
      2.7 times higher percentage of CA than the other heart failure patients.
      CONCLUSION: Increased levels of sTNFRII identify a heart failure patient subgroup
      with high CA activity.

PMID- 11983203
TI  - Diagnostic value of peripheral blood T-cell activation and soluble IL-2 receptor
      for acute rejection in liver transplantation.
AB  - BACKGROUND: T-cells play an important role in the pathogenesis of rejection.
      Monitoring T-cells activation markers in peripheral blood may contribute to
      diagnosis of acute rejection after liver transplantation (LTX). METHODS:
      Lymphocyte subset distribution, expression of T-cell activation markers (flow
      cytometry), concentration of soluble (s) interleukin-2 receptor (IL-2R) (solid
      phase chemiluminescence immunoassay), and liver enzymes as well as bilirubin were
      prospectively tested in peripheral blood samples of LTX patients with (n=69) and
      without acute rejection (n=50). Acute rejection was assessed by standard criteria
      including liver biopsies. RESULTS: Intra-individual monitoring of immune
      parameters revealed an up-regulation of IL-2 receptor (CD25) expression on CD4
      and CD8 T-cells together with increases in sIL-2R levels in patients with acute
      rejections. Measuring sIL-2R levels resulted in highest diagnostic efficiency
      (>85%). This level of diagnostic efficiency was not reached by any other marker
      tested. From all conventional markers of hepatocellular integrity and function,
      alkaline phosphatase reached the highest level of diagnostic efficiency with 70%.
      CONCLUSIONS: Monitoring of up-regulation of the IL-2/IL-2R pathway represents a
      useful tool for assessment of acute rejection after LTX.

PMID- 11983204
TI  - Simple high-density lipoprotein cholesterol assay based on dry chemistry.
AB  - BACKGROUND: Currently, high-density lipoprotein cholesterol (HDL-C), a factor
      which prevents progression of arteriosclerosis, is measured using laboratory
      based chemistry analyzers without a pretreatment step. Because HDL-C is measured
      with a pretreatment step in many point-of-care testing systems, a direct assay is
      needed. METHODS: A dry-chemistry-based assay using surfactants has recently been
      developed in parallel with the development of a dedicated reagent. A simple
      analyzer that accepts whole blood samples was also developed. RESULTS: The assay
      demonstrated excellent precision, dilution linearity and intermethod comparison.
      In an interference test, assay values tended to be lower in the presence of high
      concentrations of hemoglobin, conjugated or unconjugated bilirubin. Neither
      ascorbic acid up to 20 mg/dl, nor formazin turbidity up to 2100, had an effect on
      the assay. CONCLUSIONS: This dry-chemistry assay using only surfactants for
      specificity in the direct HDL-C method was judged useful for point-of-care
      instrumentation in terms of equipment compactness, operational simplicity and
      rapid responsiveness.

PMID- 11983205
TI  - Quantification of the influence of mycophenolic acid on the release of
      endothelial adhesion molecules.
AB  - BACKGROUND: Mycophenolic acid selectively inhibits inosine 5'-monophosphate
      dehydrogenase leading to a shortage of guanosine nucleotides. Since GTP is
      required for the synthesis of glycoproteins, this immunosuppressive drug also
      influences the production of several cell adhesion molecules. METHOD: Soluble
      endothelial cell adhesion molecules released into cell culture supernatants after
      an incubation period of 16 h are assessed via a standard ELISA procedure applying
      test kits for E-selectin, VCAM-1 and ICAM-1. RESULTS: Treatment with TNF-alpha
      leads to the induction of E-selectin and causes a significant increase in VCAM-1
      and ICAM-1 content in the supernatant in relation to the level of unstimulated
      cells. Due to the inhibitory effects of MPA-applied either alone or in
      combination with cyclosporin A and prednisolone-sE-selectin is significantly
      reduced and sVCAM-1 is slightly but not significantly decreased, whereas sICAM-1
      levels remain unchanged. CONCLUSIONS: We demonstrate that the influence of MPA on
      endothelial cell adhesion molecules can readily be determined via ELISA. The
      results indicate that the immunosuppression by MPA is also achieved by slightly
      reducing the expression and consequent release of E-selectin, a pivotal molecule
      in the first step of leucocyte-endothelial interactions.

PMID- 11983206
TI  - Measurement of corticoids in the patients with clinical features indicative of
      mineralocorticoid excess.
AB  - BACKGROUND: A method for the measurement of five important serum and urinary
      corticoids on the syndrome of mineralcorticoid excess is reported. The
      methodology was combined gas chromatography-mass spectrometry (GC-MS) with
      selected ion-monitoring mode. METHODS: After extraction with a solid-phase
      cartridge using an Oasis HLB copolymer, the residues were derivatized with a
      mixture of N-methyl-N-trimethylsilyltrifluoroacetamide/ammonium
      iodide/dithioerythritol (1000:4:5, v/w/w), and analyzed. RESULTS: The linearity
      as the regression coefficients were >0.979 over a range of 1-500 ng/ml, and limit
      of detection ranged from 1 to 3 ng/ml while their analytical recoveries varied in
      the range of 75.7-94.9%. The overall precision (% CV) of the method were 3.2-7.2%
      and 3.6-6.3% for serum and urine, respectively. The accuracy expresses as % bias
      ranged from -4.1 to 6.4%. This assay was used on two patients with hypokalemic
      hypertension, and may be useful in ruling out mineralcorticoid excess (AME) type
      1 or 2. CONCLUSIONS: The present GC-MS technique may be useful to differentiate
      between the syndrome of AME and other hypertensive diseases with clinical
      features suggestive of mineralcorticoid excess because of the assay's reliablity
      and precision.

PMID- 11983207
TI  - Expression of BRCA1 and BRCA2 in different tumor cell lines with various growth
      status.
AB  - BACKGROUND: BRCA1 and BRCA2 are breast cancer susceptibility genes. Recent
      studies suggest that BRCA1 interacts with a great variety of proteins, including
      BRCA2, cell-cycle regulators, transcriptional activators and repressors. We
      investigated the expression of both BRCA1 and BRCA2 during the progression of the
      cell cycle of human tumor cell lines from different origins (MCF7, MDA-MB231, PA1
      and CCL221) in two growth status (60% and 100% of confluency). METHODS: First,
      the growth status was characterized by determination of the cell cycle by flow
      cytometry analysis. At the same time, immunohistochemistry was performed to
      follow BRCA1 and BRCA2 protein expression and then, quantification of BRCA1 and
      BRCA2 transcripts was realized using real-time quantitative RT-PCR. RESULTS: We
      reported in studied tumor cell lines with 60% of confluency by comparison with
      100% of confluency, an increase in the BRCA1 and BRCA2 expression at the level of
      proteins and transcripts. CONCLUSION: Therefore, the expression of both BRCA1 and
      BRCA2 genes at the protein and mRNA levels appear to be up-regulated after cell
      proliferation in human tumor cell lines from different origins.

PMID- 11983208
TI  - Serum oxidative and antioxidant parameters in a group of Italian patients with
      age-related maculopathy.
AB  - OBJECTIVES: The purpose of this study was to measure the oxidative and
      antioxidant biochemical parameters in the serum of Italian patients with age
      related maculopathy (ARM) and in a similar age control group from the same area,
      in order to determine the weight of oxidative status as risk factor in the early
      stage of macular degeneration onwards. DESIGN AND METHODS: Forty-eight ARM
      patients (19 early and 29 late form) and 46 normal subjects, similar for age, sex
      and life-style, were studied. A series of serum and/or plasma antioxidants
      (vitamins C, E, A, total and individual carotenoids, zinc, total plasma
      antioxidant capacity--TRAP) and oxidative parameters (reactive oxygen metabolites
      -ROM, oxidized-low-density lipoprotein antibodies-anti-Ox-LDL) were evaluated in
      both groups, also with regard to age and disease stage. RESULTS: Levels of
      vitamins C, E, total carotenoids and beta-cryptoxanthine were lower in late ARM
      than in early ARM (p<0.05). Of the serum carotenoids investigated, only lycopene
      was lower in the two ARM forms than in controls (p<0.05). The main biochemical
      parameters, TRAP, zinc, anti-Ox-LDL and ROM were similar in the two groups.
      CONCLUSIONS: A deficit of antioxidants (vitamins C, E and carotenoids) seems to
      be associated with ARM in Italian patients, particularly the advanced form, it is
      also suggested that in ARM patients macular susceptibility to oxidative damage is
      not related with age.

PMID- 11983209
TI  - Serum time course of two brain-specific proteins, alpha(1) brain globulin and
      neuron-specific enolase, in tick-born encephalitis and Lyme disease.
AB  - METHODS: Time courses of the serum concentrations of two brain-specific proteins
      (BSP), alpha(1) brain globulin (alpha(1)BG, an astroglial marker) and neuron
      specific enolase (NSE), were studied in patients with severe tick-born
      encephalitis (TBE) and Lyme disease (LD; neuroborreliosis). The concentrations
      were determined on the second day of the acute phase and then on the 7th, 12th,
      18th, and 23rd days. Apparent rate constants for the elimination of the BSP from
      blood (k(e)) were calculated with the non-linear regression. RESULTS: In patients
      with TBE, the highest serum concentrations of alpha(1)BG and NSE, observed on the
      second day, were followed by their monotonic decrease to the normal levels
      reached by the 23rd day. The mean k(e) values for alpha(1)BG and NSE were found
      to be significantly different (0.086+/-0.003 vs. 0.057+/-0.006 day(-1),
      respectively; p<0.05). Higher serum levels of both BSP were observed in the more
      severe clinical cases and in the cases with unfavorable outcomes. Similar
      profiles were also observed for the serum alpha(1)BG and NSE in LD. CONCLUSIONS:
      These results suggest that, in the patients examined, the blood-brain barrier was
      partially impaired; the quantitative parameters of the serum BSP time courses can
      be indicative of the extents of the neuronal and/or glial lesions.

PMID- 11983210
TI  - Protection of prostatic acid phosphatase activity in human serum samples by
      plasmin inhibitors.
AB  - BACKGROUND: The level of prostatic acid phosphatase in serum is an established
      marker for prostate carcinoma. METHODS: Inactivation of homogeneous prostatic
      acid phosphatase from human seminal fluid by purified plasmin and human serum was
      studied in the presence and absence of bovine pancreatic trypsin inhibitor, a
      plasmin inhibitor, or phenylmethylsulfonylfluoride, a serine protease inhibitor.
      RESULTS: Plasmin or serine protease inhibitors protect against prostatic acid
      phosphatase inactivation in serum samples. CONCLUSION: The immediate addition of
      serine protease inhibitors to serum samples taken for prostatic acid phosphatase
      determinations should provide more accurate results and permit extended storage
      of samples. The stabilization of the enzyme activity and immunological properties
      of prostatic acid phosphatase in blood samples by these protease inhibitors
      resurrects the clinical significance of prostatic acid phosphatase measurements
      in prostate cancer screenings.

PMID- 11983211
TI  - Glucocorticoids and increased serum cystatin C concentrations.

PMID- 11983212
TI  - The mutagenically separated polymerase chain reaction is a rapid and reliable
      method for genotyping of the tumour necrosis factor-alpha promoter polymorphism (
      308 G/A).
AB  - BACKGROUND: The tumour necrosis factor-alpha (TNF alpha) promoter polymorphism (
      308 G/A) has been shown to be associated with the susceptibility to and/or the
      severity of diverse diseases such as infections, autoimmunity, and malignancies.
      We developed a genotyping technique based on the mutagenically separated
      polymerase chain reaction (MS-PCR) which may be useful in the clinical risk
      assessment. METHODS: Different length allele-specific primers and an unspecific
      complementary strand primer were used in a one-tube assay. At least one PCR
      product was generated in a single reaction obviating the need for an internal
      control amplification. Introduction of additional base substitutions into the
      allele-specific primers led to a clear-cut separation between the alleles through
      the reduction of cross-reactions during amplification. The only post-PCR step
      required was the separation of allelic PCR products by size upon agarose gel
      electrophoresis. RESULTS: The allele frequencies in 300 German healthy Caucasians
      were 0.84 for TNF1 (-308 G) and 0.16 for TNF2 (-308 A) in accordance with
      published data obtained with the conventional RFLP method. No significant
      deviation from Hardy-Weinberg equilibrium was observed. The specificity of MS-PCR
      was confirmed by sequence-based typing. CONCLUSIONS: MS-PCR is a rapid, reliable,
      and cost-effective technique for genotyping of the TNF alpha promoter
      polymorphism (-308 G/A).

PMID- 11983215
TI  - Electrospray mass spectrometry for the identification of MHC class I-associated
      peptides expressed on cancer cells.
AB  - Electrospray ionisation (ESI) mass spectrometry (MS) has been used extensively
      for the detection of peptides presented by major histocompatibility complex (MHC)
      molecules. This review focuses on the optimisation of electrospray mass
      spectrometry and the use of tandem mass spectrometry to sequence MHC class I
      peptides. We review the isolation of MHC class I peptides from the surface of
      cells with particular reference to tumour cells. In addition, we also discuss the
      advantages and disadvantages of the methods available to concentrate and
      fractionate the peptides prior to analysis by electrospray mass spectrometry.

PMID- 11983216
TI  - A rapid ELISA-based serum assay for myelin basic protein in multiple sclerosis.
AB  - We have developed a sensitive, ELISA-based assay to detect autoantibodies to
      myelin basic protein (MBP) in human serum. Autoantibody levels were measured in
      98 normal healthy adults (age range 20-66) and 94 clinically definite multiple
      sclerosis (MS) cases (age range 18-63). Of the MS patients, 77% had elevated
      levels of MBP autoantibodies (IgG) whereas only five normal individuals had
      antibody levels increased over normal. From the receiver-operator curve (ROC),
      the mean+/-2SD as clinical decision limit offers high sensitivity (77%) and
      specificity (95%). No change in assay performance was observed when hemoglobin,
      triglycerides or bilirubin were added to serum samples. The success of the assay
      is dependent on the use of heparin, an anionic molecule, which neutralizes the
      positive charge on the highly cationic MBP.

PMID- 11983217
TI  - Development of a diagnostic test for Entamoeba histolytica using idiotype
      expression in human.
AB  - The protozoan parasite Entamoeba histolytica is the etiological agent of human
      amebiasis. The pathology of the disease starts with the cytolysis of the host
      target cells by amoebae. It is initiated by the adhesion of trophozoites to the
      host cells, through surface lectin via specific receptors. These adherence
      lectins have been demonstrated to be highly conserved, and can be recognised by
      serum antibodies from patients with invasive amebiasis. Some of these molecules
      have been used as antigens in serologic studies, which has been very helpful in
      the diagnosis of invasive intestinal amebiasis. However, false-positive serologic
      reactivity can occur using E. histolytica extracts and purified antigens.
      Additional problems are because the extracts display a great enzymatic activity.
      Several diagnostic methods, using different molecules and techniques, have been
      described. However, the problem still remains since these tests are not capable
      of differentiating between amoebic liver abscess (ALA) and intestinal
      amebiasis.Here, the research has been addressed to the 66-kDa antigen, which is a
      part of the outer membrane proteins from the E. histolytica strain HM1-IMSS
      trophozoites. First of all, we characterized the 66-kDa antigen in order to prove
      the relevance. We found that the 66-kDa antigen is a part of the plasma membranes
      and is distributed rather homogeneously on the cell surface of trophozoites.
      Apparently, the 66-kDa antigen is a glycoprotein. Using a monoclonal antibody
      (MAb), we found 25% of inhibition in the erythrophagocytosis by the trophozoites.
      Starting form one monoclonal antibody, we prepared an anti-idiotype (anti-Id)
      antibody reagent, with the purpose of searching for the different expressions of
      the idiotype between the sera from ALA and the intestinal amebiasis patients.
      Moreover, we produced the antibody Ab3 that is capable of recognising the 66-kDa
      antigen; it means that the Ab2 displays the internal image of the antigen. We
      found that 91.6% of the serum from ALA patients displayed the expression of the
      Id. In contrast, 15.7% of the E. histolytica asymtomatic cyst carriers displayed
      the Id expression, 6.6% of the patients with another parasite infection, and 11%
      of the negative controls (serum from umbilical cords of newborn babies). Our
      results showed that the expression of the Id could be differentiated among the
      AHA patients from the other groups with a 91.6% sensibility and 88.3%
      specificity.

PMID- 11983218
TI  - Quantitation of secretory group V phospholipase A(2) in human tissues by sandwich
      enzyme-linked immunosorbent assay.
AB  - We have developed a sensitive sandwich ELISA (sELISA) for quantitative
      determination of group V phospholipase A(2) (gVPLA(2)). This assay utilizes three
      monoclonal antibodies (mAbs) directed against human gVPLA(2) (MCL-1B7, MCL-2A5,
      and MCL-3G1), which recognize specifically different epitopes of gVPLA(2). A
      mixture of MCL-1B7 and MCL-2A5 was used as the capture mAb, and MCL-3G1 as the
      detector mAb; purified human gVPLA(2) was used as the standard protein. The limit
      of detection of the sELISA is 2 ng/ml; the intra- and inter-coefficients of
      variation were 4.97+/-0.81% and 8.42+/-3.4%. The validity of the sELISA was
      assured by the recovery of exogenous recombinant gVPLA(2), which was 99.7% to
      102%, and demonstration of noninterference of the gVPLA(2) assay by a high
      concentrations of other protein from murine lung and heart. To assess the
      usefulness of this sELISA for tissue measurements, the amount of gVPLA(2) in
      cultured human epithelial cells and isolated human eosinophils was determined.
      Total gVPLA(2) mass in epithelial cells was 2.83+/-0.33 ng/10(7) cells; gVPLA(2)
      was not detected in eosinophils. The presence of high concentration of gVPLA(2)
      in epithelial cells was confirmed by immunoprecipitation/Western blot analysis
      and by flow cytometry. This assay allows for convenient differentiation between
      the highly homologous 14-kDa secretory PLA(2)s, gVPLA(2), gIIaPLA(2), gIbPLA(2)
      and gXPLA(2), and accurate quantitation of gVPLA(2) in biological samples.

PMID- 11983219
TI  - Flow cytometric "rare event analysis": a standardized approach to the analysis of
      donor cell chimerism.
AB  - Lack of standardization of methods and detection limits contributes to the
      controversial results regarding microchimerism after organ transplantation and
      has prompted the development of a standardized, reproducible, "easy-to-use" flow
      cytometric method for this type of "rare event analysis".EDTA-blood of healthy,
      HLA-typed donors was stained simultaneously with FITC- and biotin-labeled HLA
      class I antibodies (One Lambda) as well as Cy5-PE-labeled CD45 (Medac, Hamburg)
      according to a standard protocol and analysed on a Coulter EPICS XL Flow
      cytometer (FCM). An absolute range of positivity (mean MESF+/- 1 STD) was
      determined for 22 HLA-specific antibodies. The range of positivity ranged between
      5000 and 20,000 MESF (anti-A23, 24(9) FITC) and 40,000-140,000 (anti-Bw6 FITC).
      The frequency of nonspecific positive signals using nonstained cells, isotype
      controls and irrelevant HLA antibodies was between 0.01% and about 0.5%, in some
      samples up to 1.4%, with an MESF between 8000 and 150,000, thus interfering
      clearly with the defined positive range of most antibodies tested. Using an "HLA
      antibody cocktail", combining FITC- and PE-labeled antibodies for different HLA
      specificities and thereby creating an internal control, the identification of
      donor cells was improved but was only rarely applicable. Due to the lack of
      highly reactive antibodies, FCM analysis was not suitable for the reliable
      identification of very low numbers of donor hematopoetic cells despite the
      theoretical advantages of flow cytometric detection of rare events. The single
      parameter approach was hampered by a significant frequency of nonspecific
      positive signals, which were easily mistaken as specific (true) positive signals,
      whereas the multiparameter approach could only be used in selected cases.

PMID- 11983220
TI  - Ex vivo expansion of functional T lymphocytes from HIV-infected individuals.
AB  - This study was designed to define the conditions for expansion of functional T
      lymphocytes from human immunodeficiency virus (HIV)-infected subjects, with the
      ultimate goal of using these cells for immunotherapy. The most appropriate
      culture conditions for good T cell proliferation included stimulation with anti
      CD3 and anti-CD28 coated microspheres, and propagation in Aim V serum-free media
      with 20 U/ml interleukin-2 (IL-2), supplemented with decreasing concentrations of
      serum for the initial 8 days. Under these conditions, a 14-day culture period
      yielded approximately a 10,000-fold expansion of T lymphocytes from HIV-infected
      donors. The cultured cells comprised approximately 15% CD4+ cells and 70% CD8+
      cells. These cells retained functional capacity as assessed by cytotoxicity
      towards HIV proteins, and production of IL-2 and interferon-gamma (IFN-gamma).
      Viral replication within the culture system was controlled, but not eliminated,
      without the requirement for antiviral agents. These culture conditions were
      demonstrated to be suitable for larger scale expansion of cells in hollow fibre
      bioreactors. This methodology provides a suitable means of producing large
      quantities of functional T cells for use in autologous immunotherapy protocols.

PMID- 11983221
TI  - Advantages of hydrophobic culture bags over flasks for the generation of monocyte
      derived dendritic cells for clinical applications.
AB  - Dendritic cells (DC), potent antigen presenting cells capable of activating both
      naive and primed T cells, are currently being pursued clinically in the
      development of cancer vaccines. Variations in the literature regarding DC source,
      culture conditions, maturation state, dose, and route of immunization make
      comparisons of clinical trial data difficult. In order to define and optimize the
      culture conditions for DC generation, we have performed a careful comparison of
      two culture methods, as well as different methods of DC maturation. Our studies
      demonstrate that high viability DC can be produced and matured in gas permeable
      hydrophobic culture bags. These cells express surface molecules characteristic of
      DC and have superior yield, viability, and function to cells cultured in plastic
      tissue culture flasks. These results suggest that hydrophobic culture bags are
      ideal for the preparation of clinical DC vaccines, as DC can be generated,
      antigen-loaded, and matured in a closed system, a scheme we have found to be
      superior to previously described flask culture methods.

PMID- 11983222
TI  - Immunomagnetic separation reagents as markers in electron microscopy.
AB  - Antibodies coupled to magnetic particles have been employed for immunomagnetic
      cell isolation, but their consequent use for electron microscopy (EM) has not
      been evaluated. We used commercial antibodies coupled to iron-dextran to isolate
      T cells and monocytes/macrophages by immunomagnetic adsorption from normal human
      peripheral blood mononuclear cells. Subsequently, we studied the association of
      electron-dense immunomagnetic reagents with cell membranes. CD14-positive
      monocytes/macrophages isolated from fixed peripheral blood mononuclear cells
      retained electron-dense beads on the plasma membrane, while live cells
      internalized them. Flow cytometry and electron microscopy measurements of the
      percentage of cells that bound a CD4-specific immunomagnetic reagent in pan-T
      cell isolates (containing numerous T cell subtypes) were indistinguishable. The
      immunomagnetic reagent associated with cells could be secondarily labeled by
      secondary antibody coupled to colloidal gold. This study shows that these
      reagents used for cell isolation or just labeling, remain associated with their
      targets at the cell membrane. Immunomagnetic reagents allow "capturing" of rare
      cells from complex mixtures, purifying and concentrating them in a single step
      for subsequent electron microscopy. The large number of commercially available
      immunomagnetic reagents specific for different human, mouse and rat antigens
      provides additional resources for visualization of cellular ultrastructure.

PMID- 11983223
TI  - Autoantibody detection in type 2 autoimmune hepatitis using a chimera recombinant
      protein.
AB  - Autoantibodies against cytochrome P450 2D6 (CYP2D6), known as anti-liver/kidney
      microsome type 1 (LKM1) and/or anti-human formiminotransferase cyclodeaminase,
      formally known as anti-liver cytosol type 1 (LC1) define type 2 autoimmune
      hepatitis (AIH). The aims of this work are to develop a sensitive and specific
      test to detect anti-LKM1 and/or anti-LC1 autoantibodies and to establish the
      prevalence of anti-LC1. Sera from children with type 2 AIH (n=48) and those from
      a control group (n=100) were evaluated for anti-LKM1 and anti-LC1 by Enzyme
      Linked Immunosorbent Assay (ELISA) and Western blotting. Each serum sample was
      assayed for reactivity against formiminotransferase cyclodeaminase and CYP2D6
      alone or as part of a recombinant chimera protein. By ELISA with recombinant
      chimera protein, 50 serum samples were positive, 48 from patients with type 2 AIH
      and 2 from patients with chronic hepatitis C. Twenty-five of 48 (52%) patients
      studied were positive for both CYP2D6 and LC1 autoantibodies. Anti-LC1, either as
      the only marker or associated with anti-LKM1, was positive in 34/48 (71%). By
      Western blotting, anti-LC1 was found in 27/48 (56%) patients. This ELISA
      technique has proven to be antigen-specific and more sensitive than Western blot
      for the detection of anti-LC1 and anti-LKM1 autoantibodies. The prevalence of
      anti-LC1 (71%) confirms it as an important immunomarker in type 2 AIH.

PMID- 11983224
TI  - Sensitive detection and quantitation of mouse eosinophils in tissues using an
      enzymatic eosinophil peroxidase assay: its use to rapidly measure pulmonary
      eosinophilia during experimental respiratory syncytial virus infection of mice.
AB  - Eosinophils are granular proinflammatory leukocytes implicated in the
      pathogenesis of several inflammatory processes including allergy, asthma, and in
      the development of enhanced disease during respiratory syncytial virus (RSV)
      infection. Here, we adapted a colorimetric assay to measure eosinophil peroxidase
      (EPO) activity in inflamed mouse lung tissue in order to quantitate pulmonary
      eosinophilia during experimental RSV infection. Using the substrate o
      phenylenediamine dihydrochloride (OPD) in the presence of bromide ions, we show
      that this assay is able to quantitate limiting numbers of eosinophils in lung
      tissue homogenates even in the presence of large numbers of infiltrating
      neutrophils and macrophages. The ability of the EPO assay to selectively
      quantitate eosinophils in a complex tissue inflammatory infiltrate demonstrates
      the usefulness of this enzymatic assay as a rapid and sensitive method to
      quantitate the influx of eosinophils into inflamed mouse tissue such as the lung
      during experimental RSV infection without reliance on morphologic criteria to
      identify murine eosinophils in tissues or bronchial lavage fluid.

PMID- 11983225
TI  - Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay.
AB  - We have developed a microtiter assay for evaluating basophil spontaneous adhesion
      to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine
      induced basophil adhesion to bovine serum albumin (BSA). The percentage of
      basophils adhering to either ECM or BSA was quantified by the histamine content
      of the adhering basophils. The spontaneous adhesion to fibronectin was higher
      than to laminin and collagen type I. Both spontaneous adhesion to fibronectin and
      interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte/macrophage colony
      stimulating factor (GM-CSF) induced adhesion to BSA increased with time between 5
      and 45 min. The histamine release in both spontaneous and induced basophil
      adhesion was lower than 3.1%. This microtiter assay is simple and reproducible
      and can be applied for basic and clinical studies using a limited number of
      partially purified basophils.

PMID- 11983226
TI  - Comparison of murine Epo ELISA and Epo bioassays in detecting serum Epo levels
      during anemia associated with malaria infection.
AB  - A highly sensitive sandwich ELISA specific for murine erythropoietin (mEpo) was
      developed using commercially available monoclonal anti-mouse Epo antibody and
      polyclonal anti-human Epo antibody. This newly developed Epo ELISA protocol and
      the traditional Epo bioassay method were used to analyze Epo production in
      response to anemia induced during blood-stage Plasmodium chabaudi AS (P. chabaudi
      AS) malaria infection in C57BL/6 mice. Both methods revealed an inverse
      correlation between the serum Epo concentration and hematocrit level, but Epo
      values estimated by the Epo bioassay were between 5- and 20-fold higher than
      those estimated by the ELISA. Further study demonstrated that the estimated Epo
      level in bioassay was strongly influenced by other cytokines present in the
      samples. Therefore, the Epo bioassay detects the net erythropoiesis promoting
      activities, whereas the ELISA method specifically measures the level of Epo in
      the samples. Combined with the Epo bioassay, the murine Epo ELISA will be an
      extremely useful tool in specifically measuring the Epo response and facilitating
      the understanding of mechanisms involved in the development of anemia-associated
      diseases using mouse models.

PMID- 11983227
TI  - The establishment of a combined serum-free and serum-supplemented culture method
      of obtaining functional cord blood-derived human mast cells.
AB  - BACKGROUND: Serum-free cultures supplemented with stem cell factor (SCF) and IL-6
      is reported to support the extensive growth of less functional human cord blood
      derived mast cells. OBJECTIVE: To obtain more functional mast cells from cord
      blood, we developed a culture system combining a serum-free condition for 0-8
      weeks of culture, and followed by a serum-supplemented culture condition and
      examined the function of the cells compared to the cells cultured continuously in
      serum-free condition. METHODS: Human cord blood progenitors were purified with
      anti-CD133 antibody. They were cultured in a serum-free medium StemSpan
      supplemented with SCF at 100 ng/ml and IL-6 at 50 ng/ml for 8 weeks. Then, an
      aliquot of the cultured cells were cultured in the above condition but further
      supplemented with 10% fetal calf serum (FCS). RESULTS: The addition of FCS after
      8 weeks of culture significantly increased the amount of histamine per mast cell
      (3.8 pg/cell) when compared to the serum-free condition (0.7 pg/cell). The cells
      cultured with FCS after 8 weeks expressed more FcvarepsilonRI alpha and released
      >30% of the histamine content upon anti-IgE stimulation than those cultured
      without serum. CONCLUSION: It is uncertain why FCS enhanced the functional
      maturation of mast cells when added after week 8 of culture but suppressed mast
      cell development when added at day 0 of culture. Yet, the present method
      combining a serum-free culture system with a serum-supplemented culture system
      seems to be beneficial for most of the laboratories to obtain functional human
      mast cells.

PMID- 11983228
TI  - A novel bulk-culture method for generating mature dendritic cells from mouse bone
      marrow cells.
AB  - We established a novel culture method for generating dendritic cells (DC) from
      mouse bone marrow (BM) cells. Unfractionated bulk BM cells were cultured in the
      presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      interleukin-4 (IL-4) for 5-7 days and a DC population was isolated by gradient
      centrifugation with 14.5% (w/v) metrizamide. Through this method, 30-40 x
      10(6)/mouse DC with 85-95% purity was obtained on day 7; this yield was higher
      than those of conventional DC generated by Inaba's method either with GM-CSF
      alone (conventional-GM DC) or GM-CSF and IL-4 (conventional-GM/4 DC). Bulk
      cultured DC have a more matured phenotype than both conventional-GM and -GM/4 DC
      as shown by higher expression of CD86, MHC class II and CD40. Functional analyses
      reveal that (1) bulk-DC show less ability in endocytosis than conventional-GM DC
      and are comparable in IL-12 p70 production with conventional-GM and -GM/4 DC. (2)
      Bulk-DC exhibit stronger stimulatory capacity in allogeneic T-cell proliferation
      than conventional DC. (3) By using ovalbumin (OVA) and OVA-specific T-cell
      receptor (TCR) transgenic mice (DO11.10) system, OVA protein-loaded bulk-DC
      stimulated CD4 T cells of DO11.10 mice more than conventional-GM DC and
      comparable with conventional-GM/4 DC. (4) Furthermore, OVA peptide-pulsed bulk-DC
      stimulated CD4 T cells more than conventional-GM and -GM/4 DC. These data
      indicate that bulk-DC are functionally more mature than conventional DC. Taken
      together, bulk-culture method is a simple technique for generating functionally
      mature BM-DC in large quantities and high purity.

PMID- 11983229
TI  - Determination of P-gp and MRP1 expression and function in peripheral blood
      mononuclear cells in vivo.
AB  - P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) mediate
      the efflux of many therapeutic agents and have been implicated in the treatment
      failure of many infectious diseases and cancers. The ability to characterise the
      expression and function of these transporters in vivo is important when assessing
      the pharmacological activity of drugs. We investigated some of the problems
      involved in screening the multidrug resistance status of individuals using flow
      cytometry. Expression of P-gp and MRP1 on the surface of lymphocytes isolated
      from blood samples (30 ml) was determined by indirect immunofluorescence.
      Functional ability was assessed by measuring the efflux of specific fluorescent
      dyes. Results were expressed as a mean fold increase in fluorescence from the
      isotype control (expression) and a change in fluorescence compared to the load
      (function). Using these assays, we determined the expression of P-gp to be 2.01+/
      0.40, n=30 and MRP1 to be 1.46+/-0.23, n=25. Functional ability was 6.98+/-4.97,
      n=25 for P-gp and 1.55+/-0.25, n=25 for MRP1. The dye efflux studies were
      associated with a lack of specificity and a number of methodological
      difficulties. There was no correlation between the expression and function of P
      gp (r=0.338; p=0.10) or MRP1 (r=0.283; p=0.17). Therefore, we considered
      determination of P-gp and MRP1 expression to be a more reproducible and accurate
      approach to clinical investigation into the role of multidrug resistance.

PMID- 11983230
TI  - Ex vivo detection and enumeration of human antigen-specific CD8+ T lymphocytes
      using antigen delivery by a recombinant vaccinia expression vector and
      intracellular cytokine staining.
AB  - We describe an intracellular cytokine staining, flow cytometry based technique
      for quantitative and qualitative assessment of CD8+ T lymphocyte-mediated antigen
      specific immune responses. This adaptation of the technique first described by
      Suni et al. [J. Immunol. Methods, 212 (1998) 89; Cytometry, 40 (2000) 60]
      utilises a recombinant vaccinia expression vector to deliver the test antigen to
      the MHC class I processing pathway. This allows the measurement of antigen
      specific CD8+ T cell responses in human subjects, irrespective of HLA type, and
      un-restricted to responses directed against a single peptide epitope. This method
      offers an advantage over the ELISPOT methods because the cells producing cytokine
      in the assay can be readily phenotyped, and it permits the simultaneous analysis
      of multiple cytokines. Finally, this technique does not require the prior
      establishment of autologous transformed B cell lines from patients/subjects.

PMID- 11983231
TI  - A novel ultrasound-enhanced latex agglutination test for the detection of
      antibodies against Mycobacterium tuberculosis in serum.
AB  - A novel ultrasound-enhanced latex agglutination test is described for the
      detection of serum antibodies against Mycobacterium tuberculosis. The use of
      ultrasound to detect the low level of antibodies in serum enhances the
      sensitivity of the test. The technique is based on the fact that suspended latex
      particles become concentrated in an ultrasonic standing wave field, thereby
      increasing the rate of particle-particle collisions compared to the standard
      agglutination test procedure. Reactions were performed on piezo-ceramic wafers,
      which were connected to an oscillator at a frequency of 100 kHz. This method
      improved sensitivity significantly so that even 20 times diluted serum samples
      exhibited agglutination, which was clearly visible to the naked eye.

PMID- 11983232
TI  - Evaluation of IFNalpha bioavailability by MxA mRNA in HCV patients.
AB  - Previously, we have reported the development of a new quantitative-competitive
      polymerase chain reaction (qc-PCR) method to evaluate interferon-beta (IFNbeta)
      bioavailability in multiple sclerosis (MS) patients, by measuring mRNA of
      mixovirus resistance protein A (MxA). Here we show that our assay is also able to
      assess IFNalpha bioavailability in hepatitis C virus (HCV) patients treated with
      different IFNalpha regimens. Indeed, our method was able to detect a slight
      constitutive expression of MxA mRNA in untreated HCV patients (median=70
      fgMxA/pgGAPDH) and a significant induction 12 h after the first IFNalpha
      administration (median=750 fgMxA/pgGAPDH).

PMID- 11983233
TI  - A model system for optimising the selection of membrane antigen-specific human
      antibodies on intact cells using phage antibody display technology.
AB  - The functional expression of human antibody fragments on the surface of
      filamentous bacteriophage, and selection of phage antibodies (PhAbs) with
      antigens, has provided a powerful tool for generating novel antibodies.
      Applications of phage antibody display technology have increased over the past
      decade. Successful isolation of phage antibodies has been reported mostly using
      purified antigens. Isolation has proven to be more complicated with complex
      mixtures of antigens, such as intact cells. A given cell type contains thousands
      of different epitopes, each capable in theory of binding phage antibodies. Often
      antigens are not known or cannot be purified without disrupting their
      conformational integrity. To overcome problems involving phage antibody
      selections on intact cells, we have developed an experimental model system that
      allows for optimisation and comparison of various selection strategies. The model
      system comprises labelling of intact cells with the fluorescently labelled
      phospholipid fluorescein-DHPE. Upon incubation, this phospholipid is readily
      incorporated in the membrane of any cell type. Labelling intensity is regulated
      by varying the phospholipid concentration. After optimisation of key steps in the
      selection procedure, we were able to isolate fluorescein-DHPE specific phage from
      a synthetic library using intact cells. This model system can be applied to any
      cell type and we demonstrate that it can be used to efficiently compare and
      optimise selection strategies.

PMID- 11983234
TI  - Mapping the C terminal epitope of the Alzheimer's disease specific antibody
      MN423.
AB  - The mapping of monoclonal antibody epitopes is now predominantly carried out
      using molecular diversity techniques, phage display in particular. However, until
      very recently, phage display methods have been inappropriate for the analysis of
      epitopes that require a free carboxy terminus. Here we describe the use of two
      different techniques to analyze the known C terminal epitope specificity of
      MN423, a monoclonal antibody specifically staining truncated tau in Alzheimer's
      brain. Using a lambda phage based C-terminal random peptide library, and an
      intracellular expression library based on truncated tau, we show that this
      antibody has an absolute requirement for a glycine at position -3 with respect to
      the C terminus. Both methods give similar results, and identify other important
      residues in the binding site. However, affinity analysis of synthetic peptides
      revealed that the affinity of the antibody for identified tripeptides was far
      lower than the pentapeptide sequence in the native target, and that this in turn
      was considerably below the affinity for the native target itself. This suggests
      that molecular diversity methods may define minimum, but not necessarily complete
      epitopes. The methods described here have a general application to the analysis
      of antibody epitopes suspected to be found at the C terminus.

PMID- 11983235
TI  - Large-scale bacterial fermentation and isolation of scFv multimers using a heat
      inducible bacterial expression vector.
AB  - This protocol describes optimised large-scale bacterial fermentation conditions
      for recombinant single-chain Fv molecule (scFv) monomers and multimers (diabodies
      and triabodies). The heat-inducible bacterial secretion vector, pPOW3, utilising
      the temperature-regulated tandem lambda promoters is particularly suited to the
      large-scale fermentation of single-chain antibodies, providing low-cost
      recombinant protein synthesis. The protein expressed by this vector is secreted
      into the periplasm where it is found as both the soluble and insoluble protein
      that is associated with the cell membranes. A protein fractionation method for
      the rapid extraction and affinity purification of the soluble protein fraction
      and the urea solubilization and refolding of the insoluble protein fraction
      expressed from single-chain antibody (Ab) fragment gene constructs is described.
      This method is simple to perform and utilises inexpensive reagents to provide
      cost-effective protein synthesis.

PMID- 11983239
TI  - Nobel Symposium 119: Global HIV Therapeutics--HIV Vaccines. 7-9 June 2001,
      Stockholm, Sweden.

PMID- 11983240
TI  - Past, present and future of HIV vaccine trials in developing countries.
AB  - A safe, effective and accessible preventive vaccine is our best long-term hope
      for the control of the HIV/AIDS pandemic. The first phase I trial of an HIV
      vaccine was conducted in the US in 1987. Since then, >30 candidate vaccines have
      been tested in over 60 phase I/II clinical trials, involving >8000 healthy human
      volunteers. The majority of these trials have been conducted in the US and
      Europe, however, trials have also been conducted in developing countries (Brazil,
      China, Cuba, Haiti, Kenya, Thailand, and Uganda), including an ongoing phase III
      efficacy trial of a rgp120 candidate vaccine in Thailand. The effort to develop
      and evaluate HIV vaccines must increase, especially in Africa.

PMID- 11983241
TI  - Politics, the media and science in HIV/AIDS: the peril of pseudoscience.
AB  - The microchip, the computer and the DNA revolution have brought the questions of
      ethics, counselling and equitable research to the fore. The new world order is a
      world of: equity; human rights; human dignity; the alleviation of poverty;
      closing the gap between the "haves and have nots". The social and economic impact
      and implications of these have opened a new dialogue between the professions and
      the laypersons in order to address matters of rights, ethics and power
      relationships in health research that is unprecedented in history. The yearning
      need for science to be understood by the public; the need for scientists to
      communicate better; the need for the public to make choices about what science
      has to offer in their daily life; the need for the public to participate and
      shape the scientific process; the need for science to integrate the wealth of
      information that is already existent has never been greater than today. Perhaps
      no examples illustrate these challenges better than the revolution in biology
      (the Human Genome Project and embryo stem cell research/therapy) and the human
      immunodeficiency virus (HIV)/AIDS epidemic that is sweeping sub-Saharan Africa
      (1). The way we teach, learn and practice science will no longer be the same. It
      will no longer be business as usual. It is unfortunately also within this context
      that pseudoscience is likely flourish (2).

PMID- 11983242
TI  - HIV vaccines: the Uganda experience.
AB  - By late 1980s Uganda was the epicenter of the AIDS epidemic in the world but
      strong preventive interventions and committed leadership has turned the epidemic
      round. HIV incidence and prevalence have declined but infection rates remain
      unacceptably high, making HIV vaccine research a priority. Uganda pioneered the
      first HIV vaccine trial in Africa but had to overcome ethical, scientific and
      logistical challenges. Preparation for HIV vaccine evaluation (PAVE) studies
      started in 1994 involving 3000 subjects followed up for 2 years. Results provided
      information on HIV vaccines acceptability, behavioral change, prevalence and
      incidence of HIV and gave indication for future successful HIV vaccine trial. In
      1996, preparation for HIV vaccine trial of ALVAC (Clade B) HIV vCP205 to test for
      safety, immunogenicity and cross-clade reactivity started by building consensus
      in Uganda and addressing scientific, ethical, social, legal and political issues.
      The study recruited 40 healthy HIV negative volunteers (20 received the vaccine,
      20 controls). The experience and skills gained forms a basis for more HIV vaccine
      trials and we will draw on this experience, and more trials using ALVAC (Clade A)
      HIV vaccine in both adults and children are being planned as a follow up.

PMID- 11983243
TI  - HIV vaccine evaluation center in Rio de Janeiro, Brazil.
AB  - We conducted an HIV seroincidence study among high-risk men who have sex with men
      in Rio de Janeiro to determine whether this population would be suitable for
      vaccine and non-vaccine HIV prevention studies. There were 34 HIV seroconversions
      during the follow-up period, for a seroincidence of 3.1 per 100 person-years. The
      incidence among the youngest members of our cohort was over 8%, an
      extraordinarily high transmission rate for a homosexual male population. We have
      used the sensitive/less sensitive ELISA assay to identify a high-risk
      heterosexual population for intervention studies in Brazil. The estimated
      seroincidence was 1.9 and 2.8 per 100 person-years among heterosexual females and
      males, respectively. We are presently conducting a study to investigate behavior
      changes among 202 participants of a post-sexual-exposure chemoprophylaxis (PEP)
      study. During a median follow-up of 24 months, there were 11 HIV seroconversions,
      10 of which were among non-PEP users. Additionally, we are conducting a phase 2
      HIV vaccine trial of the ALVAC-HIV vector vCP1452 alone and in combination with a
      subunit vaccine, MN rgp120, in healthy adult volunteers. The primary goal of this
      trial is to define the immunogenicity and confirm the safety of the most
      promising vector-based vaccine alone and in combination with a recombinant
      envelope protein vaccine with an established safety and immunogenicity profile. A
      phase 3 HIV vaccine trial is planned to begin in the next 18-24 months.

PMID- 11983244
TI  - Immunity, immunopathology and vaccines against HIV?
AB  - Immunity and immunopathology of HIV infections leading to AIDS are reviewed from
      an evolutionary point of view. Accordingly infectious agents and host defences
      have co-evolved to reach balanced states where virus and host survive. While HIV
      has not quite yet reached an optimal balance, tuberculosis (TB), leprosy, HBV,
      HCV in humans or lymphocytic choriomeningitis virus (LCMV) in mice have
      successfully established persistence. These non- or poorly-cytopathic infections
      infect the next host usually before or at birth while hosts are
      immunoincompetent. They also infect immunocompetent hosts to persist at low
      levels concomitant with an ongoing T and B cell immune response that is
      repeatedly triggered by latent or persistent infection of extralymphatic or
      lymphatic host cells. This infectious or infection-immunity is the basis for
      cellular immunoprotection by antigen activated T cells. Because we cannot imitate
      this infection-immunity long-term and cannot build polyspecific vaccine
      combinations covering all possible neutralising variants yet, vaccines against
      TB, leprosy, HCV and HIV only protect transiently and incompletely.

PMID- 11983245
TI  - HIV T cell vaccines, the importance of clades.
AB  - Development of an HIV vaccine presents a formidable challenge. One of the
      unresolved, yet central issues is the importance of HIV variability. Here we
      argue that even with the recent focus on the induction of T cell-mediated
      immunity, HIV vaccines should match the local circulating HIV clades. Whether
      used alone or in a combination with vaccines eliciting HIV-neutralizing
      antibodies, efforts must be made to develop a T cell vaccine that stimulates a
      broad and long-lasting response.

PMID- 11983246
TI  - Passive transfer studies to elucidate the role of antibody-mediated protection
      against HIV-1.
AB  - In order to understand immune correlates of protection and to develop effective
      immunization strategies, it is important to know if antibodies can confer
      protection against HIV-1 infection or disease. The recent development of the
      pathogenic simian/human immunodeficiency virus (SHIV)-macaque model based on env
      genes from primary HIV-1 isolates permits the in vivo evaluation of anti-HIV-1
      envelope glycoprotein immune responses. Using this model, we and others initially
      showed that passively infused antibody can protect against an intravenous SHIV
      challenge. However, HIV-1 is most often transmitted across mucosal surfaces and
      the intravenous challenge model may not accurately predict the role of antibody
      in protection against mucosal exposure. We, therefore, adapted the SHIV89.6PD
      model to allow evaluation of anti-HIV-1 antibodies against vaginal challenge. In
      order to make comparisons to our prior intravenous challenge study, we used the
      same SHIV89.6PD stock and antibodies. Our data show that antibodies can confer
      protection against vaginal exposure to a pathogenic SHIV; if virus transmission
      occurs, their presence can ameliorate the subsequent pathogenic manifestations of
      virus infection. Compared to our previous intravenous challenge study, greater
      protection was achieved after vaginal challenge. Because the highest level of
      protection occurred when the most potent combinations of antibodies were used,
      the data confirm that in vitro neutralization assays on peripheral blood
      mononuclear cells (PBMC) targets cells are a relevant measure of protective
      antibody activity.

PMID- 11983248
TI  - HIV and lymphocyte dynamics.

PMID- 11983247
TI  - Analysis of the immune response and viral evolution during the acute phase of SIV
      infection.
AB  - Development of an effective vaccine against human immunodeficiency virus (HIV)
      will require knowledge of the immune responses that correlate with protection.
      During the acute phase of HIV infection the host immune responses appear to
      control viral replication. It is thought that virus-specific cellular immunity is
      intimately involved in this viral control. We have developed a model system to
      measure the entire T cell response and viral evolution in the face of this
      onslaught in rhesus macaques during the acute phase of infection with molecularly
      cloned simian immunodeficiency virus (SIV). We used intracellular cytokine
      staining (ICS) of peripheral blood mononuclear cells (PBMCs) from animals during
      the acute phase of viral infection stimulated with peptides spanning the entire
      protein sequence of SIV to determine which peptides were recognized by CD8 and
      CD4 positive T cells. Furthermore, we sequenced the entire virus during the acute
      phase of infection. This approach has proved highly effective for measuring acute
      phase T cell responses and viral evolution in SIV-infected rhesus macaques and
      might facilitate the definition of cellular immune responses in HIV-infected
      humans during the acute phase.

PMID- 11983249
TI  - Understanding the basis of CD4(+) T-cell depletion in macaques infected by a
      simian-human immunodeficiency virus.
AB  - The efficacy of candidate AIDS vaccines to mediate protection against viral
      infection and pathogenesis is evaluated, at a preclinical stage, in animal
      models. One model that is favored because the infecting virus is closely related
      to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of
      Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We
      investigated the basis for the depletion of CD4(+) T lymphocytes in a SHIV
      macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the
      ability to cause CD4(+) T-cell loss at a given level of virus replication in
      monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane
      fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins
      of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that
      specifies this increase in membrane-fusing capacity was sufficient to convert
      SHIV-89.6 into a virus that causes profound CD4(+) T-cell depletion in monkeys.
      Conversely, two single amino acid changes that decrease the membrane-fusing
      ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4(+) T-cell
      destruction that accompanied a given level of virus replication in SHIV-infected
      monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes,
      which has been implicated in the induction of viral cytopathic effects in vitro,
      contributes to the capacity of the pathogenic SHIV to deplete CD4(+) T
      lymphocytes in vivo.

PMID- 11983250
TI  - Innate T cell immunity to HIV-infection. Immunotherapy with phosphocarbohydrates,
      a novel strategy of immune intervention?
AB  - Natural T (NT) lymphocytes recognize infected cells or microbial compounds
      without the classical genetic restriction of polymorphic major histocompatibility
      complex (MHC) molecules. NT cells are mainly composed of alphabeta and gammadelta
      T lymphocytes that express natural killer (NK) receptors and recognize
      preferentially various nonpeptidic antigens. Similar to NK cells, NT lymphocytes
      can see and kill target cells deficient in the expression of one or more MHC
      class I molecules. NT cells expressing the alphabeta TCR can recognize lipid and
      lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules,
      whereas phosphocarbohydrates and alkylamines induce constitutive response of
      Vgamma9Vdelta2 T cells. The stimulation of Vgamma9Vdelta2 T cells with
      phosphocarbohydrates induces the production of cytokines (IFNgamma and TNFalpha)
      and the release of chemokines with suppressive activity on HIV replication. In
      addition, stimulated Vgamma9Vdelta2 T cells exert a cytolytic activity against
      HIV-infected targets. In HIV-infected patients, a quantitative and qualitative
      alteration is observed early during the infection. Vgamma9Vdelta2 T cells are
      deleted and the remaining gammadelta cells are anergic. Th1 cytokines (IL-12 and
      IL-15) positively regulate cytokine production by Vgamma9Vdelta2 T cells but they
      are inefficient in restoring normal functions in patients' gammadelta T cells.
      Interestingly, partial restoration of the immune system under highly active
      antiretroviral therapies (HAART) is associated to the recovery of functional
      Vgamma9Vdelta2 T cells. A large panel of phosphocarbohydrates able to selectively
      stimulate Vgamma9Vdelta2 T cells is currently available, and preliminary
      experiments in monkeys suggest their in vivo efficacy in helping to control SIV
      replication. These observations prompt the question of new immune intervention
      involving molecules that stimulate NT cells.

PMID- 11983251
TI  - HIV vaccine strategies.
AB  - Traditional methods of vaccine development have not produced effective vaccines
      for several prevalent infectious diseases, including AIDS, malaria and
      tuberculosis. These difficult diseases call attention to the importance of new
      approaches that profit from modern technologies. Successful efforts in the past
      have typically taken advantage of naturally occurring, protective immune
      responses, but this avenue is not readily available in certain cases, such as in
      HIV infection, where the immune system rarely confers protective immunity.
      However, there are alternative strategies and areas of research that may
      facilitate the development of highly effective vaccines. These include the
      identification of immunogens that elicit broadly neutralizing antibodies,
      determination of the molecular and cellular basis for immune responses to the
      components of the infectious agent, the identification of relevant forms of viral
      proteins for antigen presentation, stimulation of relevant T-cell types, and
      enhancement of antigen-presenting, dendritic cell function. Answering these basic
      research questions will aid in rational vaccine design. It is also extremely
      important to optimize techniques for the testing and production of new vaccines
      including the quantitation of immune responses in animals and in humans,
      identification of surrogate markers of immune protection, streamlined vaccine
      production, and rapid evaluation of candidate vaccines for testing in clinical
      trials. We have put these ideas into practice in two recent studies in which we
      generated enhanced cytotoxic T lymphocyte (CTL) responses, while retaining robust
      humoral responses, to wild-type viral proteins by immunizing mice with
      genetically modified forms of HIV-1 Env, Gag and Pol delivered in the form of
      plasmid DNA expression vectors.

PMID- 11983252
TI  - Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA
      vaccine.
AB  - Heterologous prime/boost regimens have the potential for raising high levels of
      immune responses. Here, we report that DNA priming followed by a recombinant
      modified vaccinia Ankara (rMVA) booster has controlled a highly pathogenic
      immunodeficiency virus challenge in a Rhesus macaque model. Both the DNA and rMVA
      components of the vaccine expressed multiple immunodeficiency virus proteins. Two
      DNA inoculations at 0 and 8 weeks and a single rMVA booster at 24 weeks
      effectively controlled an intrarectal challenge administered 7 months after the
      booster. These highly promising findings provide hope that a relatively simple
      multiprotein DNA/MVA vaccine can help to control the AIDS epidemic.

PMID- 11983253
TI  - Passive immunization with human neutralizing monoclonal antibodies: correlates of
      protective immunity against HIV.
AB  - Passive immunization with synergistic combinations of human monoclonal antibodies
      (mAbs) directed against conserved epitopes of the human immunodeficiency virus
      (HIV) envelope completely protected 13 out of 16 rhesus monkeys challenged
      intravenously or orally with chimeric simian-human immunodeficiency virus (SHIV)
      strains; partial protection was seen in another two. A high degree of protection
      was seen among orally challenged neonates. Thus, we propose that passive
      immunization with synergistic combinations of neutralizing human mAbs may be
      effective in preventing maternal HIV transmission when given as post-exposure
      prophylaxis at birth and as prophylaxis against milk-borne transmission. Because
      we only used mAbs with well-defined epitope specificities, our studies also yield
      key information for designing AIDS vaccines: the correlates of immune protection.
      Vaccine strategies that can evoke antibody responses to epitopes recognized by
      the mAbs used in our primate studies could be important components of successful
      AIDS vaccines.

PMID- 11983254
TI  - The critical role of CD4(+) T-cell help in immunity to HIV.
AB  - Vaccine-induced immunity to HIV/AIDS is a world wide health priority and a
      necessity in order to prevent or curb the transmission of this infection in the
      different human populations at risk. Failing to prevent infection, it would be
      desirable to generate sufficient immunity to control viremia in individuals which
      become infected, given that this would provide sufficient protection to prevent
      progression to AIDS. From several different pre-clinical settings data revealed
      that although CTL or neutralising antibodies were necessary immune responses for
      protection from infection, they were alone or together insufficient for providing
      solid protective immunity. What was invariably necessary was a strong specific
      CD4(+) T-cell response. Protective T-helper responses were not skewed towards an
      IFN-gamma (Th1) or IL-4 (Th2) type response, but were balanced and characterised
      by the presence of a strong Ag-specific IL-2 response.

PMID- 11983255
TI  - HIV and chemokines: implications for therapy and vaccine.
AB  - The unexpected encounter between the fields of chemokines and HIV has opened new
      perspectives for understanding the mechanisms of AIDS pathogenesis, as well as
      for the development of effective therapies and vaccines. An increasing body of
      evidence supports the concept that the level of CCR5-binding chemokines (i.e.,
      RANTES, MIP-1alpha and MIP-1beta) measured in vivo or ex vivo can provide an
      accurate correlate of natural or vaccine-induced protection from primate
      immunodeficiency viruses. In addition, by virtue of their unique immunomodulatory
      activities, chemokines may represent a new class of "intelligent" vaccine
      adjuvants, capable of finely tuning both humoral and cellular immune responses by
      recruiting specific cell types at the site of immunization. Chemokines that bind
      the major HIV coreceptors (i.e., CCR5 and CXCR4) are potent natural inhibitors of
      HIV, although a potential limitation to their therapeutic use is the risk of
      inducing inflammatory side-effects or of interfering with the physiology of the
      homeostatic chemokine system. However, recent data indicate that the ability of
      chemokines to block HIV infection can be uncoupled from their signaling activity.
      Thus, both modified chemokines and small derivative molecules maintaining the HIV
      inhibitory function, but devoid of receptor-activating capability, have been
      generated. Moreover, for the CC chemokine RANTES, the structural determinants of
      receptor recognition and antiviral function have been elucidated. Altogether,
      these findings provide a theoretical foundation for the rational design of safe
      and effective HIV-coreceptor inhibitors.

PMID- 11983256
TI  - Development of an oral prime-boost strategy to elicit broadly neutralizing
      antibodies against HIV-1.
AB  - Given the increasing incidence of HIV-1 infection world-wide, an affordable,
      effective vaccine is probably the only way that this virus will be contained.
      Accordingly, our group is developing an oral prime-boost strategy with the
      primary goal of eliciting broadly neutralizing antibodies against HIV-1 to
      provide sterilizing immunity for this virus. Our secondary goal is to elicit
      broadly cross-reactive anti-viral CD8(+) T cells by this strategy to blunt any
      breakthrough infections that occur after vaccination of individuals who fail to
      develop sterilizing immunity. This article describes our progress in the use of
      the live attenuated intracellular bacteria, Salmonella and Shigella, as oral
      delivery vehicles for DNA vaccines and the development of conformationally
      constrained HIV-1 Env immunogens that elicit broadly neutralizing antibodies.

PMID- 11983257
TI  - Muscle specific versus ubiquitous expression of Gag based HIV-1 DNA vaccines: a
      comparative analysis.
AB  - Most studies on DNA-based immunization have used viral promoters to drive antigen
      expression. In this study, we analyzed the properties of the commonly used CMV
      promoter, the tissue specific murine muscle creatine kinase (MCK) promoter as
      well as a hybrid MCK/CMV promoter regarding promoter activity and tissue
      specificity in vitro. Furthermore, the efficiency of inducing HIV-1 Gag specific
      immune responses in vivo following intramuscular immunization of naked DNA
      containing a codon optimized synthetic gene was compared. Although antibody
      titers and cellular immune responses using the MCK construct were slightly
      reduced as compared to conventional CMV based vector modules, the utilization of
      nonviral promoters may add significantly to the safety of future DNA vaccines.

PMID- 11983258
TI  - Efficiency of a myogenic DNA vaccine is strictly dependent upon cellular
      localization of HIV-1 Pr55(gag).
AB  - Most studies on DNA-based immunization have used viral promoters to drive antigen
      expression. Recently, the use of tissue-specific DNA vaccines has been favored
      regarding safety issues. In this study, we determined the impact of antigen
      localization and tissue-specific expression on the induction of humoral as well
      as cellular immune responses in a BALB/c mouse model. Thereby, we show that using
      the muscle-specific muscle creatine kinase (MCK) promoter/enhancer the efficiency
      of immune stimulation is strictly dependent on the ability of HIV-1 Pr55(gag) to
      be released from cells. By contrast, localization of Pr55(gag) and derivatives
      thereof plays only a minor role when antigen is constitutively expressed using
      the ubiquitous viral CMV promoter.

PMID- 11983259
TI  - Mechanisms of protection against simian immunodeficiency virus infection.
AB  - One of the obstacles to the development of an effective AIDS vaccine has been the
      limited information on the mechanisms of protective immunity to HIV. In macaques,
      immunization with attenuated simian immunodeficiency viruses (SIV) has proved to
      be one of the most effective strategies to induce protection against infection or
      disease with pathogenic lentiviruses. Infection with attenuated SIV strains
      induces a broad range of SIV-specific immune responses, including relatively
      potent cytotoxic T lymphocyte (CTL) and antibody responses. Several studies of
      macaques vaccinated with attenuated SIV have demonstrated correlations between
      CTL responses or antibody responses and protection but more detailed studies are
      needed to document the relative importance of these responses in protective
      immunity.

PMID- 11983260
TI  - HIV subtypes and recombination strains--strategies for induction of immune
      responses in man.
AB  - Clinical and experimental studies of HIV-1 subcomponents were made in order to
      increase their immunogenicity. HIV subtype envelopes A, B and C have been
      compared and a detailed analysis made by peptides of the coreceptor-ligand
      interactions. We identified a direct interaction between HIV-1 envelope and a
      cellular receptor at the amino acid level. Both the viral subtype and its tropism
      appeared to influence inhibition of infection. Genetic immunization induced new
      cytotoxic responses while proteins appeared to efficiently boost previous
      responses. One HIV-1 subtype B antigen was strongly immunogenic in a human
      immunotherapeutic trial and permitted better survival at 2 years of the study in
      patients with poor prognosis.

PMID- 11983261
TI  - Development of a DNA-MVA/HIVA vaccine for Kenya.
AB  - Without going into the details of the devastation that human immunodeficiency
      virus (HIV) infection causes especially in the developing world, the best hope
      for changing the course of this epidemic is development of a safe, effective,
      accessible prophylactic HIV vaccine. While the inaccessibility of potentially
      neutralising epitopes on primary HIV isolates has hampered the development of
      envelope-based vaccines, there is a number of new potent technologies capable of
      inducing high levels of circulating virus-specific CD8(+) cytotoxic T lymphocytes
      (CTL). Our original finding that a successive immunisation with DNA and modified
      vaccinia virus Ankara (MVA) vaccines expressing a common immunogen is a potent
      way of inducing CD8(+) CTL, which has been since reinforced by us and others,
      prompted us to test this approach in humans. With the view of proceeding into a
      high-risk cohort in Kenya for the efficacy trial, we designed the immunogen,
      termed HIVA, to match the HIV strain responsible locally for over 70% infections.
      It consists of a consensus clade A gag p24/p17 and a string of clade A-derived
      CTL epitopes. Pre-clinical studies demonstrated high immunogenicities of both the
      pTHr.HIVA and MVA.HIVA vaccines. In mice, these induced strong T cells-mediated
      immune responses which lasted at least 155 days. In rhesus macaques, the prime
      boost immunisation elicited T cell responses specific for multiple HIV-derived
      epitopes. Phase I trials in healthy low-risk volunteers have commenced in Oxford
      and Nairobi, and the preliminary immunogenicity analysis from the Oxford site
      indicated that both vaccine components alone induced T cell responses in a
      majority of volunteers. These results have boosted expectations for the prime
      boost vaccinations.

PMID- 11983262
TI  - Issues for improving multiplasmid DNA vaccines for HIV-1.
AB  - Since the first reports of plasmid vaccines, there have been substantial changes
      made to the design of plasmid backbones, as well as to the antibiotic resistance
      markers chosen for clinical vectors compared with first generation vectors. These
      changes aid manufacturing, production and scale up and at the same time aid
      conceptual safety by limiting the ability of the vaccines to transfer useful
      genetic selection genes to other bacterial infectious agents. In contrast, there
      has been little change to the original promoters or polyadenlyation tracts in the
      last decade. We have learned that these first generation plasmid vaccines for HIV
      1 appear very well tolerated in humans. However, while safe and immunogenic,
      improving the immune potency of DNA vaccines is a critical goal for this
      technology. The combination of antigens used should be carefully examined for
      possible immune interference. Such interference may only become apparent when
      each component of the vaccine is tested individually. This interference also
      suggests one mechanism of immune pathogenesis possibly by HIV-1. Optimization of
      the immune response can come through manipulation of the transfection efficiency,
      expression or through the use of various T cell and B cell plasmid adjuvants. It
      is likely that the combination of such advancements will significantly improve
      the clinical phenotype of this important vaccine modality.

PMID- 11983263
TI  - Therapeutic vaccination in primary HIV infection, the Quest trial.

PMID- 11983264
TI  - Engineered Listeria monocytogenes as an AIDS vaccine.
AB  - Listeria monocytogenes (Lm) is an attractive vector to elicit T cell immunity
      because it infects antigen-presenting cells and because infection originates at
      the mucosa. Lm expressing HIV gag elicits sustained high levels of gag-specific
      CTL in mice. Since Lm causes disease in immunocompromised hosts, a highly
      attenuated strain of Lm that requires D-Ala for viability was produced.
      Attenuated bacteria expressing HIV-1 gag (Lmdd-gag) are as efficient as wild-type
      recombinants at stimulating gag-specific murine CTL when administered with D-Ala
      and at boosting human CTL in vitro. Lmdd-gag immunization protects mice from
      vaccinia-gag challenge and induces mucosal CTL, even after systemic immunization.

PMID- 11983265
TI  - The advantage of early recognition of HIV-infected cells by cytotoxic T
      lymphocytes.
AB  - Accumulating evidence indicates that cytotoxic T-lymphocytes (CTL) play an
      important role in the clearing of primary and control of chronic human
      immunodeficiency virus (HIV) infection. Here, we discuss recent findings that
      indicate that the timing of target cell recognition critically contributes to CTL
      effectiveness. In this light several problems that have troubled CTL research are
      discussed. The use of early proteins like Tat and Rev is proposed for future
      vaccines design.

PMID- 11983266
TI  - A tribute to Dr Francis Roe: 50 years of outstanding achievement.

PMID- 11983267
TI  - Francis J.C. Roe--and a galvanizing trail.

PMID- 11983268
TI  - Reflections on the implications of multistage carcinogenesis for the nature of
      neoplasia.

PMID- 11983269
TI  - Calorific restriction: can we extrapolate from animals to humans?
AB  - Dietary restriction in animals results in a dramatic reduction of cancer
      incidence. Several attempts have been made to extrapolate this observation to the
      human situation. Recent developments in our knowledge of gene-dietary
      interactions, particularly in relation to vitamins, have been taken into account
      in a new examination of the likely effects of dietary restriction in humans, but
      this is a relatively new area of research. Epidemiological studies in relation to
      diet have also been considered, but probably need to be refined further because
      of the subtle effects of dietary interactions. Until more detailed information is
      available the extrapolation can still only be made with the utmost caution.

PMID- 11983270
TI  - Environmental tobacco smoke and cancer of sites other than the lung in adult non
      smokers.
AB  - Evidence from epidemiological studies relating environmental tobacco smoke (ETS)
      exposure to risk of cancer of sites other than the lung in adult non-smokers is
      reviewed. Problems common to many studies include small sample size, inadequate
      control of potential confounding, failure to consider the possibility of
      misclassification of smoking status, reliance on death certificate diagnosis, use
      of proxy respondents and the possibility of recall bias. A number of the studies
      have other obvious weaknesses. Publication bias is known to be a problem, with
      two very large prospective studies having reported only very limited results. For
      cancers of the digestive system, bladder and brain, there is little evidence of
      an association with ETS exposure. Some studies have reported a relationship with
      cancer of the breast, cervix or nasopharynx, but the overall evidence for these
      sites is inconsistent and inconclusive, as is that for total cancer incidence.
      All three studies of nasosinus cancer have reported a statistically significant
      association with ETS exposure, but they are small, control poorly for potential
      confounding and have other weaknesses. Taken as a whole, the epidemiological
      evidence provides little support for the view that ETS causes cancer of any of
      the sites considered.

PMID- 11983271
TI  - Organochlorine chemicals in seafood: occurrence and health concerns.
AB  - The cheap availability of chlorine gas, together with the development of
      industrial chlorinating procedures in the 20th century, led to the production of
      a wide range of organochlorine compounds many with a variety of commercial
      applications, including usage as insecticides and defoliants and polychlorinated
      biphenyls (PCBs) used as coolants in electricity supply transformers. However, it
      was soon found that many of these technologically valuable chemicals suffered
      from a major disadvantage in that they resisted biodegradation and that the
      continued use of these compounds would lead to their persistence and accumulation
      in the environment and thus enter the human food chain. Despite regulatory bans
      or strict limits on usage being imposed on organochlorine pesticides in most
      countries, these compounds continue to be detected in measurable amounts in the
      eco-system including marine life. In general, organochlorine levels in fish
      intended for human consumption are low and probably below levels likely to
      adversely affect human health. Populations at higher risk than most people are
      those subsisting largely on fish and other marine life. Additionally, fish oils
      obtained from contaminated fish, if consumed in substantial quantities by infants
      and young children, might present potential health problems if levels are not
      continually regulated. Behavioral and neurological effects have been reported in
      children and ascribed to the consumption of PCB contaminated diet including fish.
      Another current major human health concern, yet to be resolved, about
      organochlorine contaminants in the human diet relates to the potential ability of
      many of these chemicals at low doses to act as "endocrine disruptors".

PMID- 11983272
TI  - The endocrine disrupters: a major medical challenge.
AB  - Endocrine disruptors (EDs), chemicals capable of disrupting the normal
      functioning of the endocrine system, may pose a growing threat to human and
      wildlife health. These compounds can modulate both the endocrine and immune
      systems resulting in alteration of homeostasis, reproduction, development and
      behavior. The hypothesis that chemicals in the environment have caused endocrine
      disruption is discussed along with important issues in the assessment of the risk
      of such disruption. Emphasis is put on the most significant pathological effects,
      namely impacts on the male reproductive tract, female gynecological system, human
      fertility, thyroid function and the central nervous system.

PMID- 11983273
TI  - My saga with earthworms.
AB  - Earthworms have been studied as a readily available, easily maintainable and
      cheap test species to develop toxicity test systems as an alternative to in vivo
      rodent bioassays. The results obtained, mainly with metals, since the programme
      was initiated about 15 years ago, are summarized in this review. Metals proved
      more toxic to rodents than earthworms; the relative order of toxicity for
      different metals was similar in both species. The effects of metals and other
      compounds on enzyme activity [glutathione S-transferase (GST) and catalase] and
      the induction of metallothioneins in earthworms are described. It is concluded
      that useful preliminary information can be obtained in earthworms on the acute
      toxicity of inorganic metal ions and on the relative order of toxicity of groups
      of metal salts.

PMID- 11983274
TI  - Urinary tract calculi and thresholds in carcinogenesis.
AB  - Numerous chemicals administered to rodents at relatively high doses produce
      urinary tract calculi, resulting in erosions or ulcerations of the urothelium,
      consequent regenerative hyperplasia, and ultimately tumors. This is a high-dose
      (threshold) phenomenon, which appears to occur more readily in rodents than in
      primates, including humans. Several anatomic and urinary physiologic differences
      between rodents and humans affect the quantitative extrapolation from results in
      rodent bioassays to human risk assessment. For most chemicals producing tumors by
      this mode of action, human exposures are significantly lower than would be
      expected to be required for production of calculi, and therefore pose no
      carcinogenic hazard to humans.

PMID- 11983275
TI  - Influence of dietary components associated with high or low risk of colon cancer
      on apoptosis in the rat colon.
AB  - Although there is much epidemiological evidence for an interaction between diet
      and colorectal cancer risk, the mechanisms by which diet might protect against
      colorectal cancer are still unclear. Here we report the significant up-regulation
      of carcinogen-induced apoptosis in the colon of rats fed a diet containing low
      risk factors for colon cancer, namely low fat content, high calcium and high non
      digestible carbohydrate. The dose-dependent induction of apoptosis in colonic
      crypts by the carcinogen 1,2-dimethylhydrazine (DMH) was significantly greater in
      rats receiving the low-risk compared with a high-risk (high fat, low calcium, low
      non-digestible carbohydrate) diet (P<0.001). There were also significant
      interactions of colon region with DMH dose and region by diet, with the greatest
      increases in apoptosis occurring in the mid and distal regions of the colon
      compared with the proximal region. Since we have previously shown the low-risk
      diet to be non-toxic, these new results suggest a diet-induced up-regulation of
      apoptosis, which may represent a mechanism of protection against the early stages
      of carcinogenesis in the colon.

PMID- 11983276
TI  - Studies on the disposition, metabolism and hepatotoxicity of coumarin in the rat
      and Syrian hamster.
AB  - The hepatotoxicity, metabolism and disposition of coumarin has been compared in
      male Sprague-Dawley rats and Syrian hamsters. The treatment of rats for 12, 24
      and 42 weeks with diets containing 0.2 and 0.5% coumarin resulted in
      hepatotoxicity and increased relative liver weights. While levels of cytochrome
      P450 (CYP) and CYP-dependent enzymes were decreased, levels of reduced
      glutathione (GSH) and activities of UDP glucuronosyltransferase, gamma
      glutamyltransferase and GSH S-transferase were increased. In contrast, coumarin
      produced few hepatic changes in the Syrian hamster. Following a single oral dose
      of 25 mg/kg [3-14C]coumarin, radioactivity was rapidly excreted by the rat and
      Syrian hamster with the urine containing 63.5 and 89.9%, respectively, and the
      faeces 38.0 and 12.4%, respectively, of the administered dose after 96 h. The
      biliary excretion of radioactivity was greater in the rat than in the Syrian
      hamster. Analysis of 0-24-h urine samples revealed that both species were poor 7
      hydroxylators of coumarin. In the rat, treatment with 0.5% coumarin in the diet
      for 24 weeks was found to increase the urinary excretion of single oral gavage
      doses of 25 and 300 mg/kg [3-14C]coumarin. The marked species difference in
      hepatotoxicity between the rat and Syrian hamster observed in this study may be
      at least partially attributable to differences in coumarin disposition. However,
      additional studies are required to elucidate the metabolic pathways of coumarin
      in both species.

PMID- 11983277
TI  - Toxicological evaluation of chemical mixtures.
AB  - This paper addresses major developments in the safety evaluation of chemical
      mixtures during the past 15 years, reviews today's state of the art of mixture
      toxicology, and discusses challenges ahead. Well-thought-out tailor-made
      mechanistic and empirical designs for studying the toxicity of mixtures have
      gradually substituted trial-and-error approaches, improving the insight into the
      testability of joint action and interaction of constituents of mixtures. The
      acquired knowledge has successfully been used to evaluate the safety of combined
      exposures and complex mixtures such as, for example, the atmosphere at hazardous
      waste sites, drinking water disinfection by-products, natural flavouring
      complexes, and the combined intake of food additives. To consolidate the
      scientific foundation of mixture toxicology, studies are in progress to revisit
      the biological concepts and mathematics underlying formulas for low-dose
      extrapolation and risk assessment of chemical mixtures. Conspicuous developments
      include the production of new computer programs applicable to mixture research
      (CombiTool, BioMol, Reaction Network Modelling), the application of functional
      genomics and proteomics to mixture studies, the use of nano-optochemical sensors
      for in vivo imaging of physiological processes in cells, and the application of
      optical sensor micro- and nano-arrays for complex sample analysis. Clearly, the
      input of theoretical biologists, biomathematicians and bioengineers in mixture
      toxicology is essential for the development of this challenging branch of
      toxicology into a scientific subdiscipline of full value.

PMID- 11983278
TI  - Induction of UDP-glucuronosyltransferase 1 (UDP-GT1) gene complex by green tea in
      male F344 rats.
AB  - Tea is one of the most frequently consumed beverages in the world, second only to
      water. Epidemiological studies have associated the consumption of green tea with
      a lower risk of several types of cancers, including stomach, oral cavity,
      esophagus, and lung. This paper deals with the mechanism of action of tea as an
      effective chemopreventive agent for toxic chemicals and especially carcinogens.
      UDP-glucuronosyltransferase (UDP-GT) activities towards p-nitrophenol were
      markedly increased (51.8% or 1.5-fold) in rats that consumed tea compared with
      the control animals on water. Induction of UDP-glucuronosyltransferase activity
      by tea may involve the UDP-GT1 (UGT1A) gene complex of the UDP-GT multigene
      family. Therefore, a major mechanism of tea as a chemopreventive agent is
      induction of the microsomal detoxification enzyme, UDP-glucuronosyltransferase.

PMID- 11983279
TI  - In vitro genotoxicity assay of sidestream smoke using a human bronchial
      epithelial cell line.
AB  - Genotoxic effects of air contaminants, such as gaseous or particulate compounds,
      have been difficult to investigate due to inefficient methods for exposing cell
      cultures directly to these substances. New cultivation and exposure techniques
      enable treatment of epithelial cells with sample atmospheres with subsequent in
      vitro assays, as demonstrated by a new system called CULTEX (CULTEX: patent No.
      DE 19801763; PCT/EP99/00295), which uses a transwell membrane technique for
      direct exposure of complex mixtures, for example sidestream cigarette smoke, at
      the air/liquid interface. The sensitivity and susceptibility of human bronchial
      epithelial cells to this complex mixture have already been shown for cytotoxic
      endpoints. In this study, genotoxic effects of sidestream cigarette smoke at
      different concentrations were assessed using the alkaline comet assay. HFBE 21
      cells were exposed for 1 h to clean air, nitrogen dioxide or sidestream smoke.
      Exposure of the cells to sidestream cigarette smoke induced DNA strand breaks in
      a dose-dependent manner. The combination of gas phase exposure and the comet
      assay provides a realistic and efficient model for sensitive detection of DNA
      strand breaks induced by airborne and inhalable compounds.

PMID- 11983280
TI  - The 5-HT(4) receptor-induced depolarization in rat hippocampal neurons is
      mediated by cAMP but is independent of I(h).
AB  - Intracellular recordings were used to examine the mechanisms underlying the 5
      hydroxytryptamine (5-HT)4 receptor-mediated depolarization seen in CA1 region
      pyramidal cells in in vitro hippocampal brain slices. This depolarization was
      mimicked and occluded by administration of the membrane permeable cyclic
      adenosine monophosphate (cAMP) analog 8-bromo-cAMP but was unaffected by blockade
      of protein kinase A (PKA). These results suggest that 5-HT4 receptors signal this
      depolarization through a cAMP-dependent but PKA-independent mechanism. In many
      cell types, 5-HT elicits a depolarization via cAMP by facilitating Ih, a
      hyperpolarization-activated cation current. In contrast, we find no evidence for
      the involvement of Ih in this response. Rather, this depolarization may involve a
      cyclic nucleotide gated channel.

PMID- 11983281
TI  - Orexin-1 receptor immunoreactivity in chemically identified target neurons in the
      rat hypothalamus.
AB  - Immunohistochemistry and Western blotting were used to determine the distribution
      of orexin receptors in the rat brain. Strong orexin receptor 1 (OX1R)
      immunoreactivity was detected in the hypothalamus including the arcuate,
      ventromedial, and tuberomammillary nuclei that are involved in feeding
      regulation. The neuropeptide Y- and proopiomelanocortin-containing neurons of the
      arcuate nucleus, which act to stimulate or to inhibit feeding, respectively,
      displayed intense OX1R immunoreactivity by double immunostaining. Western
      blotting analysis yielded a 50-kDa major band of OX1R.

PMID- 11983282
TI  - Synaptic association of dopaminergic axon terminals and neurokinin-1 receptor
      expressing intrinsic neurons in the striatum of the rat.
AB  - We examined if axon terminals of dopaminergic neurons might make synapses upon
      neurokinin-1 receptor (NK1R)-expressing intrinsic neurons in the rat striatum. In
      a double-immunocytochemical ultrastructural study, dopaminergic terminals were
      labeled by the immunoperoxidase method for tyrosine hydroxylase (TH), while NK1R
      immunoreactivity (-IR) was revealed by the immunogold-silver labeling method.
      Some TH-immunoreactive (-ir) axon terminals formed synapses of the symmetric or
      intermediate type on NK1R-ir neuronal profiles; usually on dendritic profiles and
      rarely on somatic profiles. It was further confirmed by means of triple
      immunofluorescence histochemistry that NK1R-ir neurons in close association with
      TH-ir axon terminals showed nitric oxide synthase (NOS)- or vesicular
      acetylcholine transporter-IR. Since NK1R-expressing striatal neurons are
      segregated into cholinergic and somatostatin/NOS-containing intrinsic neurons
      (Brain Res. 631 (1993) 297; Neurosci. Lett. 310 (2001) 109), the present results
      indicate that dopaminergic neurons make synapses upon these intrinsic neurons in
      the striatum.

PMID- 11983283
TI  - Induction of tyrosine hydroxylase expression in rat fetal striatal precursor
      cells following transplantation.
AB  - Differentiation of neural stem cells into tyrosine hydroxylase (TH)-expressing
      cells was studied by cell transplantation into the various brain regions of rats
      that had received 6-hydroxydopamine lesion of the nigrostriatal pathway.
      Approximately 13.6-16.1% of survived precursor cells acquired neuronal-like
      features by expressing the neuronal marker doublecortin. Similarly, 20.7-25.7% of
      survived precursor cells differentiated into astrocytes following
      transplantation. Immunohistochemical analysis revealed that a fraction of the
      grafted precursor cells in the anterior part of the medial forebrain bundle
      (MFB), but not in the striatum and the substantia nigra of the lesioned side,
      showed strong TH immunoreactivity. This suggests that MFB is more permissive for
      induction of TH to the striatal precursor cells in vivo. The results further
      exemplify the potential of neural stem cells and the property of site-specific
      differentiation when the cells were transplanted to the dopaminergic system of
      the adult brain.

PMID- 11983284
TI  - The effects of probability and relative direction on human somatomotor
      electroencephalographic rhythms.
AB  - Classical views on the preparation of voluntary movement involve separate motor
      and cognitive processes. Recent neurophysiological evidence challenges this
      dichotomy. Recordings from within the motor cortices have demonstrated that
      cognitive factors modulate neural activity. This issue was examined in event
      related desynchronizations (ERDs) by using a goal-directed pointing paradigm. The
      ERD, which is typically recorded in response to self-paced finger movements, has
      been demonstrated to reflect specific movement parameters. Cognitive factors were
      introduced by manipulating probability and the relative direction of the
      responses in a choice reaction time task. The results demonstrated that
      probability influences the 20 Hz ERD.

PMID- 11983285
TI  - Centrifugal neurons of the octopus optic lobe cortex are immunopositive for
      calcitonin gene-related peptide.
AB  - Distribution of calcitonin gene-related peptide (CGRP)-like substance in the
      optic lobe cortex and retina of the octopus was examined immunohistochemically.
      Wheat germ agglutinin (WGA), a retrograde-transporting marker, was also used to
      label the centrifugal neurons. CGRP-immunoreactive (CGRP-IR) somata were seen in
      the inner granular cell layer, but not in the outer granular cell layer or the
      retina. CGRP-IR fibers were seen not only in the optic lobe cortex, but also in
      the retinal nerve plexus. Retrogradely labeled somata were seen in the inner
      granular cell layer, but not in the outer granular cell layer.
      Immunohistochemical double staining indicated that WGA-labeled centrifugal
      neurons were immunopositive for CGRP. These results suggested that the
      centrifugal neurons in the octopus optic lobe cortex are CGRP-like peptide
      containing neurons, and that the peptide may modulate photoreceptor cell
      functions.

PMID- 11983286
TI  - Huperzine A, a nootropic agent, inhibits fast transient potassium current in rat
      dissociated hippocampal neurons.
AB  - The actions of huperzine A (HupA), a novel cholinesterase inhibitor, on the fast
      transient potassium current (IA) were investigated in CA1 pyramidal neurons
      acutely dissociated from rat hippocampus. HupA reversibly inhibited IA (IC(50) =
      914 +/- 1 microM). The effect was voltage-independent and insensitive to
      atropine. Tacrine was eight times more potent than HupA (IC(50) = 115 +/- 2 M),
      whereas huperzine B had little effect. HupA slowed down the decay of IA and its
      recovery from inactivation. HupA had no effect on the steady-state inactivation,
      but hyperpolarized the activation curve of IA by 6 mV. The results suggest that
      HupA may act as a blocker at the external mouth of the A channel. The potential
      relevance of the inhibitory effect of HupA on IA to the treatment of Alzheimer's
      disease has been discussed.

PMID- 11983287
TI  - A -174G/C polymorphism of the interleukin-6 gene in patients with lacunar
      infarction.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role in the
      pathogenesis of stroke. A base pair substitution -174G/C in the promoter region
      of the IL-6 gene regulates IL-6 gene expression. We compared the prevalence of
      this polymorphism in patients with lacunar stroke and in an age- and sex-matched
      cohort of asymptomatic controls. Eighty-two patients with lacunar stroke and 82
      asymptomatic controls were prospectively assessed and genotyped for the -174G/C
      polymorphism in the promoter region of the IL-6 gene. Demographics and vascular
      risk factors were recorded in both groups. A brain computed tomography
      scan/magnetic resonance imaging confirmed the clinical diagnosis of lacunar
      stroke in all patients. The prevalence of CC genotype (18.3 vs. 7.3%, P=0.03),
      and the frequency of C allele (42.7 vs. 31.1%, P=0.03) were statistically
      significantly higher in patients with lacunar stroke than in asymptomatic
      controls. Expectedly, patients with lacunar stroke had a higher prevalence of
      vascular risk factors than asymptomatic controls. A logistic regression model
      showed that independent variables associated with lacunar stroke included history
      of hypertension (odds ratio (OR), 7.02; 95% confidence interval (95% CI), 3.11
      15.81), diabetes (OR, 5.37; 95% CI, 1.52-8.89), hyperlipidemia (OR, 3.43; 95% CI,
      1.04-11.25), smoking (OR, 5.84; 95% CI, 2.15-15.84), and CC genotype of the 
      174G/C IL-6 gene polymorphism (OR, 4.28; 95% CI, 1.22-15.00). These findings
      suggest that lacunar stroke might result from genetic susceptibility to
      inflammation-mediated damage in concert with atherosclerotic risk factors.

PMID- 11983288
TI  - Expression, proteolysis and activation of caspases 6 and 7 during rat C6 glioma
      cell apoptosis.
AB  - Activation of cysteinyl aspartate-specific proteases (caspases) may underlie
      apoptotic cell death in brain. Terminal, executioner caspases 3, 6 and 7 likely
      contribute to such cell death in a stimulus- and cell type-specific manner. Here
      we investigate the processing and activation of caspases 3, 6 and 7 in rat C6
      glioma cells induced to undergo apoptosis by staurosporine (STS) treatment as a
      model of apoptosis in glia. Proteolysis and activation of caspases 3 and 7 as
      determined by immunoblotting and substrate-specific cleavage assay (DEVDase)
      preceded caspase-6 proteolysis and increased VEIDase activity following STS
      treatment. Activation of caspase-6 was paralleled by cleavage of the nuclear
      envelope protein lamin-A. These results highlight temporal differences in the
      activation of the triad of executioner caspases 3, 6 and 7 during glial cell
      apoptosis.

PMID- 11983289
TI  - Neuronal differentiation of cultured human NTERA-2cl.D1 cells leads to increased
      expression of synapsins.
AB  - The synapsin family consists of three neuronal-specific phosphoproteins
      associated with dynamic reorganization of the neuronal cytoskeleton. Synapsin I
      and II are implicated in axonal and synaptic differentiation, formation and
      maintenance, whereas the function of synapsin III is not as well defined. We
      report a significant transcriptional upregulation of all three synapsins
      (synapsin I, 2.1-fold; synapsin II, 2.6-fold; and synapsin III, 5.5-fold) by
      retinoic acid-induced differentiation of NTera-2cl.D1 cells, a human paradigm for
      neuronal differentiation. The observed stronger regulation of synapsin III might
      be due to still active neurite elongation and a rather early state of presynaptic
      maturation at the time-point investigated, as synapsin III was previously found
      to be highly enriched in growth cones and during early synaptic development.

PMID- 11983290
TI  - The decline in serum choline concentration in humans during and after surgery is
      associated with the elevation of cortisol, adrenocorticotropic hormone, prolactin
      and beta-endorphin concentrations.
AB  - Serum choline concentrations decrease during and after surgery. We undertook this
      study to determine whether the decrease of choline is associated with an increase
      in stress hormones. In 16 patients undergoing abdominal surgery with general
      anesthesia, circulating choline cortisol, prolactin, adrenocorticotropic hormone
      (ACTH) and -endorphin levels were measured before, during and after surgery.
      Choline levels decreased by 41% (P<0.01) during surgery, remained 15-38%
      decreased for 48 h, and returned to preoperative values 72 h after surgery. The
      decrease in serum choline was associated and inversely correlated with the
      increase in serum cortisol (P<0.001; r = -0.642), prolactin (P<0.001; r = 
      0.756), -endorphin (P<0.001; r = -0.726) and ACTH (P<0.01; r = -0.458). In
      conclusion, we found that abdominal surgery induces a decline in serum choline
      associated with an increase in circulating cortisol, prolactin, ACTH and 
      endorphin.

PMID- 11983291
TI  - Immobilization stress induces the expression of alphaB-crystallin in rat
      hippocampus: implications of glial activation in stress-mediated hippocampal
      degeneration.
AB  - Overexpression and abnormal aggregation of a small heat shock protein, B
      crystallin, in reactive astrocytes has been implicated in various
      neurodegenerative diseases and brain tumors. To investigate the potential
      involvement of glial activation in stress-induced hippocampal damage, we analyzed
      B-crystallin gene expression in the hippocampus of immobilized rats. Male Sprague
      Dawley rats were subjected to single or repeated immobilization stress. Both
      single and repeated immobilization markedly increased the level of B-crystallin
      mRNA in the hippocampus. Repeated immobilization notably accumulated B-crystallin
      protein, with a substantial portion in the insoluble fraction. Treatment of
      primary cortical astrocytes with stress-related glucocorticoid resulted in
      considerable elevation of B-crystallin expression. The accumulation of B
      crystallin may serve as one of the important pathogenic mechanisms involved in
      hippocampal degeneration associated with stress.

PMID- 11983292
TI  - Unaltered brain levels of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2
      nonenal in Alzheimer's disease.
AB  - In recent years, an important role for the pathogenesis of Alzheimer's disease
      (AD) has been ascribed to oxidative stress. Trans-4-hydroxy-2-nonenal, a product
      of lipid peroxidation, forms stable adducts with a variety of nucleophilic
      substituents such as thiols or amino moieties. Here, we report the quantification
      of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal (HNE-dGp)
      using the specific and very sensitive method of 32P-postlabeling of
      deoxyguanosine adducts derived from nuclear DNA in neuron rich areas of the
      hippocampus, the parietal cortex, and the cerebellum of postmortem brains from
      patients with AD and age matched controls. Adduct levels were highest in the
      hippocampus, followed by the cerebellum and parietal cortex irrespective of the
      disease. Neither age, postmortem delay time, gender, nor the extent of
      neurofibrillary deposits affected tissue adduct levels in the brain areas
      examined. Although distinctively present in the human brain, the level of HNE-dGp
      adducts appears not to be useful as a biomarker for AD.

PMID- 11983293
TI  - Increased cortical expression of the orexin-1 receptor following permanent middle
      cerebral artery occlusion in the rat.
AB  - The orexins (hypocretins) have recently been implicated in neurodegeneration
      associated with narcolepsy. Therefore, the current study was designed to
      investigate changes in the expression of prepro-orexin and the orexin receptors,
      OX1R and OX2R following permanent middle cerebral artery occlusion (MCAO) in the
      rat. Six and twenty-four hours following MCAO, increased OX1R mRNA and protein
      expression (as assessed by Western blotting and immunohistochemistry) was
      detected in the ischaemic cortex compared with control tissue. In contrast,
      however, no increase in OX2R mRNA was detected at any time-point and prepro
      orexin levels in the cortex were below assay detection levels. This study shows
      that orexin receptor localization is altered following cerebral ischaemia. The
      development of selective orexin receptor antagonists will be crucial in
      establishing a role for this family of novel peptides in the mechanisms
      underlying ischaemic cell death.

PMID- 11983294
TI  - 14-3-3 in the cerebrospinal fluid of patients with variant and sporadic
      Creutzfeldt-Jakob disease measured using capture assay able to detect low levels
      of 14-3-3 protein.
AB  - A protein capture assay was used to measure 14-3-3 (-isoform) in the
      cerebrospinal fluid (CSF) of patients with either variant or sporadic Creutzfeldt
      Jakob disease (CJD). The results were compared with those obtained using Western
      blotting. Elevated levels of 14-3-3 were found in 58% of variant CJD (vCJD)
      patients and 82% of sporadic CJD (spCJD) patients using the protein capture
      assay. Using a Western blotting technique, the presence of CSF 14-3-3 was
      detected in 58% of vCJD patients and in 89% of spCJD patients. When the results
      from the protein capture assay and the Western blot were combined, 14-3-3 was
      detected in 77% of vCJD patients and in 91% of spCJD patients. These results
      suggest that although analysis of CSF 14-3-3 is not as useful in vCJD as it is in
      the sporadic form of the disease, a combination of these two techniques results
      in increased sensitivity of 14-3-3 for the diagnosis of vCJD.

PMID- 11983295
TI  - Roles of the central prostaglandin EP3 receptors in cardiovascular regulation in
      rats.
AB  - In this study, we examined the effects of an intracerebroventricular (i.c.v.)
      administration of prostaglandin E2 (PGE2) and of selective agonists for PGE2
      receptor subtypes, EP1, EP2, EP3 and EP4, on central cardiovascular regulation
      and renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats. The
      central administration of PGE2 (0.01-1.0 nmol) resulted in increases in blood
      pressure, heart rate (HR) and RSNA in a dose-dependent manner. Cardiovascular
      responses to PGE2 (0.5 nmol, i.c.v.) were attenuated by pretreatment with
      ganglionic and adrenoceptor blocking agents, but not with SC-19220 (20 nmol,
      i.c.v.), an EP1 receptor antagonist. An i.c.v. administration of the EP3 agonist
      ONO-AE-248 (50.0 nmol) resulted in an increase in RSNA with pressor and
      tachycardia responses, while administration of the EP2 agonist ONO-AE1-259 and
      the EP4 agonist ONO-AE1-329 caused transient hypotension and slight increases in
      HR and RSNA. The administration of the selective EP1 agonist ONO-DI-004 showed no
      effect. These results suggest that the central PGE2-induced activation of the
      sympathetic nerve activity with hypertension and tachycardia may depend on
      stimulation of the EP3 receptors in the central nervous system.

PMID- 11983296
TI  - Changes in [Ca2+](i) during adenosine triphosphate-induced synaptic plasticity in
      hippocampal CA1 neurons of the guinea pig.
AB  - The perfusion of adenosine triphosphate (ATP) induces long-term potentiation
      (LTP) in CA1 synapses of hippocampal slices, whereas the perfusion of ATP plus ,
      2-amino-5-phosphonovaleric acid (AP5) can result in the formation of long-term
      depression (LTD). To clarify the difference in change of intracellular calcium
      concentration ([Ca2+]i) corresponding to induction of LTP or LTD, we measured
      [Ca2+]i during the perfusion of ATP or ATP+AP5, while simultaneously recording
      evoked field potentials. In both cases, ATP (or ATP+AP5) perfusion transiently
      increased [Ca2+]i but the extent of increase of [Ca2+]i by ATP was larger than
      that caused by ATP+AP5. Thus, the larger rise in [Ca2+]i induces LTP but the
      smaller rise induces LTD. These results are consistent with the Ca2+ hypothesis
      as proposed by Lisman (Trends Neurosci. 17 (1994) 406).

PMID- 11983297
TI  - Medullary adrenergic neurons contribute to the neuropeptide Y-ergic innervation
      of hypophysiotropic thyrotropin-releasing hormone-synthesizing neurons in the
      rat.
AB  - The arcuate nucleus gives rise to approximately 80% of the neuropeptide Y (NPY)
      immunoreactive (IR) innervation to thyrotropin-releasing hormone (TRH) neurons in
      the hypothalamic paraventricular nucleus (PVN). However, the source of the
      remaining 20% is unknown. Since medullary adrenergic neurons synthesize NPY and
      also innervate the hypophysiotropic TRH neurons, we raised the possibility that
      adrenergic neurons contribute to the NPY-ergic innervation of TRH neurons in the
      PVN. Triple-labeling immunofluorescence was performed to study the colocalization
      of NPY and phenylethanolamine N-methyltransferase (PNMT)--the key enzyme of
      adrenaline synthesis--in axons in association with hypophysiotropic TRH neurons.
      NPY-immunoreactivity was observed in 74% of PNMT-IR axon varicosities apposed to
      proTRH-IR neurons, comprising 26% of all NPY-IR axons in contact with proTRH
      perikarya and dendrites in the PVN. We conclude that at least two distinct
      populations of NPY neurons innervate hypophysiotropic TRH neurons, the NPY
      neurons of the hypothalamic arcuate nucleus and the medullary adrenergic neurons
      that co-contain NPY.

PMID- 11983298
TI  - Apolipoprotein E genotype does not predict decline in intelligence in healthy
      older adults.
AB  - There is evidence of a genetic influence on the decline in cognitive performance
      of older adults, although the mechanisms responsible are unknown. A group of 767
      subjects of the Manchester University Age and Cognitive Performance longitudinal
      study volunteer group, followed up from 1985 to the present, were genotyped for
      apolipoprotein E (APOE). The data from this were related to cross-sectional and
      longitudinal trends in the Heim intelligence test score (AH4-1) using previously
      reported random-effects models (Neuropsychologia 39 (2001) 532). There were no
      significant differences in mean scores for presence compared with absence of the
      APOE4 or APOE2 genotypes (P=0.48 and P=0.51, respectively). This research does
      not demonstrate a link between intelligence and APOE genotype in older adults.

PMID- 11983299
TI  - Apolipoprotein E4 and tau allele frequencies among Choctaw Indians.
AB  - Apolipoprotein genotyping and tau haplotyping were carried out on a series of
      cases with dementia and controls from the Choctaw Nation of Oklahoma. Both the
      Apolipoprotein E4 allele frequency and the tau H2 haplotype frequency were low in
      the Choctaw compared with Caucasians and there was the possibility that the
      association between dementia and the E4 allele was weaker than in Caucasians.

PMID- 11983300
TI  - Cortical neurons of Creutzfeldt-Jakob disease patients express the urokinase-type
      plasminogen activator receptor.
AB  - Plasminogen belongs to the plasminogen activator system of cell signaling
      proteins and has recently been identified to bind to pathological prion protein
      PrPSC, but not to its normal conformer, PrPC. Plasminogen binds specifically to
      the urokinase-type plasminogen activator receptor (uPAR) to promote pericellular
      proteolysis, regulate integrin function, and mediate cell signaling. By using
      immunohistochemistry, we observed that significantly more cortical neurons in
      eight postmortem brains of patients who died with sporadic Creutzfeldt-Jakob
      disease (CJD) are immunoreactive for uPAR compared with controls. These data
      provide the pathophysiological basis for detailed analyses of the role of the
      plasminogen activator system in CJD and related diseases.

PMID- 11983301
TI  - Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with
      Alzheimer's disease compared to healthy controls.
AB  - Experiments in cell cultures indicate that accumulation of cholesterol in
      hippocampal neurons results in an accelerated cleavage of amyloid precursor
      protein into amyloidogenic components. To be eliminated from the brain,
      cholesterol is converted to 24S-hydroxycholesterol which may reflect cerebral
      cholesterol turnover. We investigated cerebrospinal fluid (CSF) concentrations of
      24S-hydroxycholesterol in a group of 14 Alzheimer's disease (AD) patients and ten
      healthy controls without any cognitive deficits or psychiatric or neurological
      disorders. To exclude potential effects of circulating plasma cholesterol on CSF
      24S-hydroxycholesterol levels, only patients and controls with cholesterol levels
      in the normal range of 150-230 mg/dl were included. We found significantly
      elevated 24S-hydroxycholesterol CSF but not plasma levels in AD patients compared
      with healthy controls. Our results demonstrate that CSF 24S-hydroxycholesterol is
      increased in AD. This effect does not seem to be triggered by plasma cholesterol
      levels since the latter did not significantly differ between groups.

PMID- 11983303
TI  - The effect of diet fed to lambs on subsequent development of Trichostrongylus
      colubriformis larvae in vitro and on pasture.
AB  - Contrasting herbage diets were fed to lambs to evaluate their effect on
      subsequent development of Trichostrongylus colubriformis larvae in faeces and on
      pasture. The diets had either no condensed tannin (CT), lucerne (Medicago sativa
      cv. Otaio), white clover (Trifolium repens cv. Tahora), or had moderate to high
      concentrations of CT, sulla (Hedysarum coronarium cv. Grassland Aokau), Lotus
      corniculatus (cv. Grasslands Goldie), L. pedunculatus (cv. Grassland Maku),
      Dorycnium pentophyllum, and Dorycnium rectum. Trials were carried out in summer
      (warm) and in autumn (cool and moist). In summer, egg viability was evaluated in
      vitro with egg hatch and larval development assays. In both seasons faeces were
      placed on pasture to compare recovery of eggs and larvae from faeces and larvae
      from herbage on the high and low fertility farmlets on the AgResearch Ballantrae
      Hill Country Research Station. D. rectum and D. pentophyllum diets decreased
      (P<0.01) egg hatching and larval development in laboratory assays relative to
      other diets. In summer, the number of larvae recovered from faeces placed on
      pasture was far greater (P<0.001) if the lambs had been fed lucerne than any
      other diet, whereas recovery was always lowest from faeces of sheep fed D. rectum
      and D. pentophyllum. Although dietary differences were lower in autumn than in
      summer, larval recoveries were lower (P<0.05) from faeces of lambs fed D. rectum
      and L. corniculatus than from white clover, lucerne and sulla diets. This study
      indicates that the diet of the host can have a significant impact on egg hatching
      and the subsequent development of T. colubriformis larvae in the laboratory and
      in the field. In particular, D. rectum consistently reduced T. colubriformis
      development. Effects measured in vitro generally under-estimated effects measured
      under field conditions.

PMID- 11983304
TI  - Effects of Ostertagia ostertagi and omeprazole treatment on feed intake and
      gastrin-related responses in the calf.
AB  - Infection with the bovine abomasal nematode, Ostertagia ostertagi, results in a
      loss of acid-secreting parietal cells and an increase in gastric pH. The effects
      of an experimental infection with Ostertagia and/or daily treatment with
      omeprazole (OMP) at 2mgkg(-1) bodyweight for four consecutive days (experiment
      days 24-27, inclusive) on voluntary feed intake, blood and tissue gastrin
      concentrations, abomasal G-cell numbers, gastric pH, and blood cholecystokinin
      (CCK) and pepsinogen concentrations were investigated in the calf. Ostertagia
      infected calves demonstrated a significant drop in feed intake between days 24
      and 27 post-infection (38%; P<0.001) and in G-cell numbers (42%; P<0.05) and
      significant increases in abomasal pH (P<0.001), fundic mucosal weight (99%;
      P<0.01), and blood gastrin (P<0.05) and pepsinogen (P<0.0001). OMP treatment of
      worm-free animals resulted in a significant drop in intake between days 24 and 27
      (30%; P<0.001) and in G-cell numbers (17%; P<0.05) and significant increases in
      abomasal pH (P<0.01) and blood gastrin (P<0.001). OMP treatment of Ostertagia
      infected animals with an existing hypergastrinaemia had no effect on feed intake,
      abomasal pH, blood gastrin or pepsinogen or abomasal G-cell numbers. Blood CCK
      concentrations were also unaffected by either Ostertagia infection or OMP
      treatment. These data suggest that: (a) the depression in feed intake associated
      with OMP in worm-free calves was not due to a side effect of drug treatment; (b)
      inappetance in Ostertagia-infected animals is closely associated with the
      parasite-induced hypergastrinaemia; and (c) the elevation in abomasal pH was a
      major factor responsible for the elevated blood gastrin concentrations seen in
      parasitised and OMP-treated animals.

PMID- 11983305
TI  - The effect of pasture species on parasitism and performance of lambs grazing one
      of three grass-white clover pasture swards.
AB  - Lamb parasitism and performance were compared on three pasture treatments:
      browntop/white clover, Yorkshire fog/white clover, and ryegrass/white clover
      swards maintained at a sward height of 5cm in each of two years by using
      continuous variable stocking management. In year 1, lamb performance (both
      suppressively drenched (SD) and trigger drenched (TD)) was similar on ryegrass
      and browntop swards but was poorer (P<0.05) on Yorkshire fog swards. In year 2,
      lamb performance (both SD and TD) was markedly better on ryegrass than on
      Yorkshire fog or browntop swards. This coincided with an increase in white clover
      content in the ryegrass/white clover swards and a decrease in white clover
      content in the browntop/white clover swards. Lamb performance was related to the
      white clover content of the swards (R2=85.4, P<0.001 and R2=77.5, P<0.001 for SD
      lambs and TD lambs, respectively). Differences among pasture treatments in faecal
      egg count (FEC) of TD lambs were greater in year 2 than in year 1 when no
      significant pasture effects were observed. In year 2, FEC was lowest in lambs
      which grazed ryegrass/white clover, intermediate in those which grazed Yorkshire
      fog/white clover and highest in lambs which grazed browntop/white clover, despite
      herbage allowance (kg herbage mass/kg lamb mass) being greater on the
      browntop/white clover and Yorkshire fog/white clover swards than the
      ryegrass/white clover swards. Circulating antibodies to gastrointestinal
      parasites were measured at the end of year 2. Antibody titres were highest
      (P<0.05) in the plasma of lambs which grazed ryegrass/white clover swards, and
      lowest in lambs which grazed browntop/white clover swards due to differences in
      levels of antibody to (P<0.05) Haemonchus contortus, Ostertagia circumcincta
      larvae and adults, but not Trichostrongylus colubriformis larvae or adults. These
      findings indicate that pasture composition, especially, the proportion of white
      clover, can help alleviate the production losses due to gastrointestinal
      parasitism. This information can provide a quick and readily adoptable practice
      for farmers who aim to reduce drench reliance and could become a key component of
      any integrated parasite control programme.

PMID- 11983306
TI  - The proteinases of Psoroptes ovis, the sheep scab mite--their diversity and
      substrate specificity.
AB  - The sheep scab mite, Psoroptes ovis, causes severe dermatitis in infected sheep
      with severe welfare and production implications. The dermatitis has the
      characteristics of an immediate hypersensitivity type reaction which, by analogy
      to other mite species, including the house dust mites (Dermatophagoides spp.), is
      likely to be invoked by a variety of allergens including mite-derived
      proteinases. Here, the proteinases in P. ovis extracts were characterised using
      substrate gel analysis, inhibitor sensitivity and their ability to degrade a
      variety of potential natural protein substrates. These analyses showed that mites
      contain several proteinases which could be differentiated on the basis of
      molecular size and inhibitor sensitivity with cysteine, metalloproteinases and
      aspartyl proteinases predominating. These proteinases degraded collagen and
      fibronectin, possibly indicative of a role in lesion initiation, they degraded
      several blood proteins, a property which may aid mite feeding and they degraded
      immunoglobulin G, possibly aiding immuno-evasion. Because proteinases,
      particularly the cysteine class, are demonstrably allergenic in other mite
      infestations, these proteinases clearly merit further immunological and
      biochemical definition.

PMID- 11983307
TI  - Distribution of Trypanosoma congolense in infected multimammate rats (Mastomys
      coucha): light and electron microscopical studies.
AB  - In an attempt to determine whether Trypanosoma congolense occurs both within and
      outside the blood vessels in an infected animal host, multimammate rats (Mastomys
      coucha) were infected with T. congolense and samples from spleen, lymph nodes,
      bone marrow, liver, kidney, lungs, brain, heart, intestines, ovaries and testes
      were collected. The tissue samples were fixed and processed for light and
      electron microscopical examination. In all the tissues examined, trypanosomes
      were found only within the lumen of large and small blood vessels, capillaries
      and sinuses. It is concluded that following entry into the blood circulation
      after intra-peritoneal infection of M. coucha, T. congolense remains restricted
      to the bloodstream.

PMID- 11983308
TI  - Evaluation of a simple sedimentation method (modified McMaster) for diagnosis of
      bovine fascioliosis.
AB  - A coprological sedimentation method is evaluated for quantification of egg
      shedding in bovine faeces. Through the inclusion of different number of Fasciola
      hepatica eggs in negative faeces, egg recovery rate and the sensitivity of the
      method were determined. The mean egg recovery rate of the technique was 76.72+/
      15.42%. The sensitivity of the method was 33.3% whenever eggs/g of faeces (EPG)
      are less than 1.5 and 100% for higher values. To improve the diagnostic accuracy
      with this technique, it is advisable to increase the sample from 10 to 30g of
      faeces when manipulating low egg shedding, which allowed for a sensitivity of
      83.3%. Regression equations were calculated to quantify the relationship between
      the number of recovered and incorporated eggs.

PMID- 11983310
TI  - GABA mechanisms and sleep.
AB  - GABA is the main inhibitory neurotransmitter of the CNS. It is well established
      that activation of GABA(A) receptors favors sleep. Three generations of hypnotics
      are based on these GABA(A) receptor-mediated inhibitory processes. The first and
      second generation of hypnotics (barbiturates and benzodiazepines respectively)
      decrease waking, increase slow-wave sleep and enhance the intermediate stage
      situated between slow-wave sleep and paradoxical sleep, at the expense of this
      last sleep stage. The third generation of hypnotics (imidazopyridines and
      cyclopyrrolones) act similarly on waking and slow-wave sleep but the slight
      decrease of paradoxical sleep during the first hours does not result from an
      increase of the intermediate stage. It has been shown that GABA(B) receptor
      antagonists increase brain-activated behavioral states (waking and paradoxical
      sleep: dreaming stage). Recently, a specific GABA(C) receptor antagonist was
      synthesized and found by i.c.v. infusion to increase waking at the expense of
      slow-wave sleep and paradoxical sleep. Since the sensitivity of GABA(C) receptors
      for GABA is higher than that of GABA(A) and GABA(B) receptors, GABA(C) receptor
      agonists and antagonists, when available for clinical practice, could open up a
      new era for therapy of troubles such as insomnia, epilepsy and narcolepsy. They
      could possibly act at lower doses, with fewer side effects than currently used
      drugs. This paper reviews the influence of different kinds of molecules that
      affect sleep and waking by acting on GABA receptors.

PMID- 11983311
TI  - GABA(B) receptor-mediated inhibition of mitral/tufted cell activity in the rat
      olfactory bulb: a whole-cell patch-clamp study in vitro.
AB  - GABA, the major inhibitory neurotransmitter involved in information processing in
      the olfactory bulb, is hypothesized to act through GABA(B) receptors by
      depressing primary neurotransmitter release at the level of olfactory nerve axon
      endings. The present study was designed to analyze GABA(B) receptor-mediated
      inhibition mechanisms by performing whole-cell patch-clamp recordings of
      mitral/tufted cell activity in the rat in vitro. To do so, GABA(B) receptor
      mediated action was mimicked by baclofen and antagonized by saclofen. Our
      protocol led us to provide an original description of GABA(B) receptor-mediated
      inhibition exerted on mitral/tufted cells. First, their spontaneous activity was
      shown to be drastically abolished by baclofen. Second, their responses to
      olfactory nerve electrical stimulation were graded by GABA(B) receptor-mediated
      inhibition. Indeed, this inhibition may be described as inducing effects ranked
      from a slight increase in response latency to a complete response
      suppression.Altogether, our results corroborate the hypothesis of a presynaptic
      extrasynaptic GABA(B) receptor-mediated inhibition influencing mitral/tufted cell
      olfactory nerve responsivity. However, the involvement of postsynaptic receptors,
      with different properties or with different anatomical locations, cannot be ruled
      out, particularly in the control of spontaneous activity. In conclusion, we
      underline that, in the vertebrate olfactory bulb, GABA(B) receptor-mediated
      action appears to contribute to make mitral/tufted cell responses more salient by
      reducing their resting activity.

PMID- 11983312
TI  - Expression and regulation of the immediate-early gene product Arc in the
      accessory olfactory bulb after mating in male rat.
AB  - Recent studies of the accessory olfactory bulb have shown that the expression of
      immediate-early genes, e.g., c-fos, c-jun and egr-1, can be used as a marker of
      neuronal activity in response to pheromonal cues. In this study, we analyzed the
      expression pattern, in response to mating, of the novel immediate-early gene
      product Arc (an activity-regulated cytoskeleton-associated protein). Arc is
      hypothesized to play a role in activity-dependent neuronal plasticity in the
      hippocampus. In a control group of male rats, only a small number of Arc
      immunoreactive cells were observed in the accessory olfactory bulb. In a mating
      group, however, a marked increase in the number of Arc-immunoreactive cells was
      observed only in the granule cell layer of the accessory olfactory bulb. The
      increase in the number of Arc-immunoreactive cells after mating was similar to
      that observed for other immediate-early genes. However, for the mating group, the
      increase in Arc-positive cells was limited to the granule cell layer. Granule
      cells have been shown to exhibit a strong synaptic plasticity in response to
      pheromonal stimulation. From these findings we suggest that Arc plays an
      important role in neuronal plasticity in the accessory olfactory bulb.

PMID- 11983313
TI  - Molecular diversity of the dystrophin-like protein complex in the developing and
      adult avian retina.
AB  - Mutations in dystrophin cause muscular dystrophy but also affect the CNS,
      including information processing in the retina. To better understand the
      molecular basis of these CNS deficits, we analyzed the molecular composition and
      developmental appearance of dystrophin and of the dystrophin-associated protein
      complex (DPC) in the embryonic and adult avian retina. We detected a
      concentration of the DPC at the vitreal border and in the outer plexiform layer
      of the adult retina. At both locations the complex had a different molecular
      composition and different developmental expression pattern. At the vitreal
      border, the complex was composed of utrophin, alpha-dystrobrevin-1, and
      dystroglycan, and was present at all stages of retinal development even before
      neurogenesis and gliogenesis. On the other hand, the complex in the outer
      plexiform layer consisted of dystrophin, beta-dystrobrevin and dystroglycan. The
      distribution of this complex changed from a diffusely distributed to an
      aggregated form during development concomitant with synapse formation in the
      outer plexiform layer. Solubilization of the retinal extracellular matrix by
      intravitreal injection of collagenase resulted in a redistribution of the complex
      at the retinal vitreal border but had no influence on the distribution of the
      dystrophin-associated proteins in the outer plexiform layer. These results
      demonstrate two types of dystrophin-like complexes in the chick retina with
      differential molecular compositions, different anchorage to the extracellular
      matrix, and different developmental expression patterns, suggesting distinct
      functions for the DPC at both locations.

PMID- 11983314
TI  - Noradrenergic modulation of functional selectivity in the cat visual cortex: an
      in vivo extracellular and intracellular study.
AB  - In vitro intracellular studies have shown that norepinephrine modulates cellular
      excitability and synaptic transmission in the cortex. Based on these effects,
      norepinephrine has been proposed to enhance the signal-to-noise ratio and to
      improve functional selectivity by potentiating strong synaptic responses and
      reducing weak ones. Here we have studied the functional effects of iontophoretic
      applications of norepinephrine during in vivo extracellular and intracellular
      recordings from neurons of the primary visual cortex of kittens and adult cats.
      Analysis of extracellular data concentrated on norepinephrine-induced changes in
      spontaneous and evoked activities, in signal-to-noise ratio, and in orientation
      and direction selectivity. Analysis of the intracellular data concentrated on
      actions of norepinephrine on spike firing accommodation, which has been shown to
      be reduced by norepinephrine in vitro, and on synaptic responses. Application of
      norepinephrine resulted in a depression of both spontaneous and evoked spiking
      activity. However, no systematic change in signal-to-noise ratio was observed.
      The suppressive effect of norepinephrine was exerted with no significant
      sharpening of direction or orientation selectivity tuning. The overall reduction
      in visual activity by norepinephrine affected the orientation tuning curves in a
      way compatible with a divisive effect, that is a normalization or gain control
      with no change in tuning width. Norepinephrine applied during intracellular
      recordings reduced the visually evoked depolarizing potentials whereas no change
      in the responsiveness of the cell to current-induced depolarizations was
      observed. In conditions of optimal visual stimulation which produced large
      depolarizations of several hundreds of milliseconds and sustained repetitive
      firing comparable to that obtained by direct current injection, we were unable to
      observe a facilitation of the evoked responses by norepinephrine as it would be
      expected from the well-documented increase in excitability induced by
      norepinephrine in vitro. In conclusion, from these results we suggest that
      norepinephrine released in the primary visual cortex primarily reduces the level
      of cortical activation by afferent signals, without affecting the cortical
      functional selectivity nor increasing the signal-to-noise ratio.

PMID- 11983315
TI  - Muscarinic receptor subtypes are differentially distributed in the rat cochlea.
AB  - Five different genes encode the muscarinic acetylcholine receptors. The
      muscarinic receptor subtypes M1, M3, and M5 are typically coupled to activation
      of the Galpha(q/11)-phosphatidyl inositol pathway, whereas the M2 and M4 subtypes
      are typically linked to Galpha(i) and adenylyl cyclase inhibition. In order to
      localize muscarinic receptors in the rat cochlea, we applied polyclonal
      antibodies for subtypes M1, M2, M3, and M5, and monoclonal antibody for subtype
      M4 to paraffin sections. In the organ of Corti, outer hair cells exhibited strong
      immunoreactivity for M3 and weak immunoreactivity for M1. Deiters' cells were
      strongly immunoreactive to antibodies for the M1 and M2 subtypes, with weak
      staining observed for M3, and weaker yet for M5. Inner hair cells showed moderate
      immunoreactivity for the M1 subtype, weaker staining for the M5 subtype, and
      slight staining for the M3 subtype. Among the spiral ganglion neurons, weak to
      moderate immunoreactivity was detected for M3 and M5 subtypes and weak staining
      was observed for the M1 subtype. The efferent fibers of the intraganglionic
      spiral bundle were positive for M2 and M5. In the lateral wall, weak to moderate
      staining was detected for M5 in the stria vascularis corresponding in position to
      the basolateral extensions of marginal cells. Staining for M3 was observed
      associated with capillaries. Fibrocytes of the spiral ligament exhibited limited
      but selective subtype immunoreactivity. No immunoreactivity was detected in the
      cochlea for the M4 subtype. From the present findings we suggest that M3 is the
      primary muscarinic receptor subtype in outer hair cells mediating a postsynaptic
      response to the medial olivocochlear cholinergic efferent input. The muscarinic
      receptor subtypes M1, M3, and M5 appear to subserve the action of cholinergic
      lateral olivocochlear efferent stimulation on postsynaptic responses in type I
      afferents. Whether M1, M3, and M5 protein in inner hair cells indicates
      constitutive or vestigial expression remaining from development is unknown. M2
      and M5 muscarinic receptors expressed presynaptically may modulate the efferent
      signal. Finally, expression by Deiters' cells of several muscarinic subtypes
      raises the possibility that cholinergic efferents couple to these non-sensory
      cells through muscarinic receptors.

PMID- 11983316
TI  - Laminar properties of 4-aminopyridine-induced synchronous network activities in
      rat neocortex.
AB  - We examined the effects of 4-aminopyridine (4-AP) on isolated horizontal
      (superficial, middle and deep) rat neocortical slices in order to study laminar
      synchronous network behavior directly. Application of 4-AP induced spontaneous
      synchronized activity in all of these types of slices. In middle and deep layer
      slices the activities were similar to those of coronal slices, consisting of
      periodic short- and long-duration discharges. In superficial slices distinct
      spontaneous rhythmic multiphasic burst discharges were induced. Ionotropic
      glutamate receptor antagonists blocked the 4-AP-induced synchronous activities in
      middle and deep layer slices, but those in superficial slices persisted. The
      GABA(A) receptor antagonist picrotoxin suppressed this spontaneous synchronous
      activity resistant to 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (a NMDA
      receptor antagonist) and 6-cyano-7-nitroquinoxaline-2,3-dione (a non-NMDA
      receptor antagonist), in superficial slices, leaving small, slow spontaneous
      events. In superficial slices with intact excitatory amino acid transmission,
      picrotoxin attenuated the 4-AP-induced spontaneous synchronous discharges, even
      in this highly convulsant environment. By contrast, conventional coronal slices
      showed robust spontaneous epileptiform discharges under these circumstances. In
      intact coronal slices focal 4-AP application in superficial layers induced
      spontaneous inhibitory GABAergic events, while delivery into deep layers led to
      epileptiform discharges. From these results we conclude that: (1) 4-AP-induced
      population discharges are driven by glutamatergic transmission in middle and deep
      layer horizontal slices, and by GABAergic transmission in superficial layers; (2)
      only superficial layers are capable of supporting synchronized GABAergic activity
      independent of excitatory amino acid transmission; (3) superficial layers do not
      sustain epileptiform activity in the absence of deep layer neurons; and (4)
      synchronized superficial networks can inhibit deep layer neuronal activity.

PMID- 11983317
TI  - Dissociation in the involvement of dopaminergic neurons innervating the core and
      shell subregions of the nucleus accumbens in latent inhibition and affective
      perception.
AB  - Mesencephalic dopaminergic neurons have been found to be involved in affective
      processes. Their implication in cognitive processes appears less well understood.
      The use of latent inhibition paradigms is a means of studying these kinds of
      processes. In this study, we investigated the involvement of dopaminergic
      projections in the core, the dorsomedial shell and the ventromedial shell of the
      nucleus accumbens, in latent inhibition in olfactory aversive learning.
      Variations in extracellular dopamine levels induced by an aversively conditioned
      olfactory stimulus were monitored in the three parts of the nucleus accumbens in
      the left hemisphere, after pre-exposure to the olfactory stimulus using in vivo
      voltammetry in freely moving rats. The parallel between dopamine changes and
      place preference or aversion toward the stimulus were analyzed in pre-exposed and
      non-pre-exposed animals. Results showed that dopaminergic neurons innervating the
      nucleus accumbens are differentially involved in the latent inhibition
      phenomenon. Dopaminergic neurons innervating the core and the dorsomedial shell
      subregions of the nucleus accumbens appeared to be involved in latent inhibition
      processes, unlike those reaching the ventromedial shell. Nonetheless dopamine in
      the ventromedial shell was found to be involved in affective perception of the
      stimulus.The present data suggest that dopaminergic neurons innervating the three
      nucleus accumbens subregions are functionally related to networks involved in
      parallel processing of the cognitive and affective values of environmental
      information, and that interaction between these systems, at some levels, may lead
      to a given behavioral output. These data may provide new insights into the
      pathophysiology of schizophrenic psychoses.

PMID- 11983318
TI  - Drug-induced rotation intensity in unilateral dopamine-depleted rats is not
      correlated with end point or qualitative measures of forelimb or hindlimb motor
      performance.
AB  - The pharmacological induction of rotational (circling) behavior is widely used to
      assess the effects of lesions to the dopaminergic system and the success of
      treatment strategies in rat models of Parkinson's disease. While the number of
      rotations under apomorphine, L-DOPA and amphetamine is related to the extent of
      dopamine depletion after unilateral 6-hydroxydopamine lesion of the nigrostriatal
      dopamine system, the relationship of the intensity of rotational behavior to the
      degree of impairment in motor behavior is unclear. The present study examined
      this question by correlating rotational behavior and motor abilities in a rat
      analogue for Parkinson's disease produced by unilateral nigrostriatal bundle
      lesion with 6-hydroxydopamine. Ipsiversive and contraversive rotation was
      measured in the rats following systemic administration of low and high doses of
      apomorphine, the dopamine precursor L-DOPA, and amphetamine. The motor assessment
      included end point and qualitative measures of fore- and hindlimbs assessed in a
      skilled reaching task and a skilled ladder rung walking task. The intensity of
      drug-induced rotation did not correlate with the measures of motor performance.
      We conclude that independence of rotational behavior and motor performance argues
      that both the assessment of 6-hydroxydopamine behavioral deficits and potential
      treatments for the functional deficits require comprehensive assessment,
      including both measures of rotation and motor behavior.

PMID- 11983319
TI  - Behavior-related modulation of substantia nigra pars reticulata neurons in rats
      performing a conditioned reinforcement task.
AB  - Motor-control models of basal ganglia function have emphasized disinhibition
      through reduction of tonic, inhibitory output. Although these models have shed
      important light on basal ganglia operations, evidence emerging from
      electrophysiological studies of behaving primates suggests that disinhibition
      alone may not adequately explain the role of the basal ganglia in movement. To
      assess this role in the rat, the most frequently used subject in studies of basal
      ganglia function, we recorded neuronal activity in the primary output nucleus,
      the substantia nigra pars reticulata, during an operant task. After rats were
      trained to nosepoke into an illuminated hole for access to a 10% sucrose solution
      delivered through a spout, single- and multiple-unit activity was recorded during
      60-120 nosepoke trials. Compared to the period 60 s before the start of the first
      trial in the task, 110 of 225 reticulata units increased firing >200% while 17 of
      225 decreased to 40% of baseline. Of these 225 units, >60% responded coincident
      with specific task events such as nosepokes and spout licking. Most nosepoke
      responsive units showed either excitation (>50%) or a combination of excitation
      and inhibition (>25%) rather than inhibition alone (>20%). Increases in firing
      were also common during approach and licking at the spout, with inhibitions alone
      comprising 30% of responses. In some units, there was evidence of reward-related
      responding, with changes occurring in anticipation of reward delivery or during
      the delivery of sucrose, but not the persistent licking that continued for
      several seconds after its offset. While 70% of units responded during both
      nosepokes and spout licking, changes in firing were typically unique depending on
      the motor behavior required (i.e. nosepoking vs. licking). Our results, which
      indicate a prominent role for increases in nigra reticulata activity during
      movement, add to growing evidence that although inhibitions may allow desired
      motor responses to emerge, excitations may help shape behavioral output by
      suppressing competing motor programs.

PMID- 11983320
TI  - Excitotoxic lesions of the pedunculopontine differentially mediate morphine- and
      d-amphetamine-evoked striatal dopamine efflux and behaviors.
AB  - Cholinergic and glutamatergic cells in the pedunculopontine tegmental nucleus are
      a principal source of excitatory input to midbrain dopamine neurons projecting to
      the striatum. Disruption of these brainstem inputs has been shown to respectively
      enhance and reduce psychostimulant and opiate self-administration in rats. In the
      present study, d-amphetamine- and morphine-induced behaviors and dorsal striatal
      dopamine efflux, measured using in vivo chronoamperometry, were investigated 21
      days after bilateral excitotoxic (ibotenate) lesions of the pedunculopontine in
      rats. Compared to sham-operated controls, pedunculopontine lesions enhanced
      stereotyped behaviors induced by a challenge injection of d-amphetamine (1.5
      mg/kg, i.p.) to an extent that markedly interfered with the expression of
      locomotor behavior. A significant augmentation in striatal dopamine efflux was
      also observed in these lesioned animals under urethane anesthesia in response to
      a similar challenge injection of d-amphetamine (1.5 mg/kg, i.v.) 2 days following
      these behavioral observations. In direct contrast, pedunculopontine lesions in a
      separate group of rats significantly attenuated morphine-induced (2 mg/kg, i.p.)
      stereotyped activity, although no significant differences were observed in
      locomotion compared to sham-operated animals. Under urethane anesthesia, these
      lesions attenuated striatal dopamine efflux evoked by a similar challenge
      injection of morphine (2 mg/kg, i.v.). These findings indicate that the
      pedunculopontine differentially mediates the pharmacological actions of two
      diverse drugs of abuse on striatal dopamine neurotransmission and resultant
      behaviors. These results also imply that the pedunculopontine tegmental nucleus
      may serve as a major striatal-motor interface in the processing of salient
      environmental stimuli, and their incentive rewarding impact on dopamine-mediated
      behavioral responses.

PMID- 11983321
TI  - Commissural connections of human superior colliculus.
AB  - The superior colliculus of higher mammals is a laminated structure of the
      midbrain that receives visual input in superficial layers, and visual, auditory
      and somatosensory input in deep layers. The superior colliculi on either side are
      interconnected via the intercollicular commissure, which has been proposed to
      play a role in visual transfer and gaze orienting. Intercollicular connections
      have been anatomically demonstrated in various species including macaque monkeys
      but not in man. Here we describe the organization of commissural connections of
      the superior colliculus in man. A single injection of the carbocyanine tracer
      1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was made into
      the superior colliculus in five post-mortem brains. Contralateral to the
      injection, labelled axons formed a dense bundle in the deep collicular layers and
      isolated axons were present in the superficial layers. Synaptic-like boutons were
      found in all collicular layers. Injections placed at different rostro-caudal
      levels revealed a roughly topographical organization; the bulk of the labelled
      axons were found opposite to the injection, with a progressive decrease in
      labelling at more rostral and caudal levels. Our results demonstrate that
      superficial and, to a larger extent, deep layers participate in intercollicular
      connections, and suggest that visual information crosses at the collicular level.

PMID- 11983322
TI  - Manipulation of inhibition in the owl's nucleus laminaris and its effects on
      optic tectum neurons.
AB  - Differences in arrival time and intensity (or level) of sound between the ears
      serve as cues for localization of sound in many animals. Barn owls use interaural
      time difference (ITD) and interaural level difference (ILD) for localization in
      azimuth and elevation, respectively. The owl's brain processes these two cues in
      separate pathways. The nucleus laminaris is the first site that detects ITDs by
      methods of delay lines and coincidence detection. The nucleus ventralis lemnisci
      lateralis, pars posterior is the first site of processing ILDs. The two pathways
      merge in the inferior colliculus to give rise to sensitivity to combinations of
      ITD and ILD. This selectivity is relayed to the optic tectum where neurons are
      sensitive to both visual and auditory stimuli. The present paper reports the
      results of manipulating inhibition in the nucleus laminaris and its effects on
      the optic tectum neurons. Injection of GABA or muscimol (a GABA(A) receptor
      agonist) in the nucleus laminaris reduces the responses of its neurons to ITD.
      This finding proves that GABA(A) receptor-mediated inhibition acts on the nucleus
      laminaris neurons. The same treatment did not affect the neurons of the nucleus
      ventralis lemnisci lateralis, pars posterior, whereas it reduced the response of
      the optic tectum neurons to ITD-ILD pairs. We conclude that although the two
      pathways are independent, the process of combining ITD and ILD creates a new
      relationship in which the output of the neuron varies with the amplitude of
      either input. This conclusion is consistent with the recent finding that the
      combination sensitivity is due to a multiplication of ITD and ILD inputs.

PMID- 11983323
TI  - Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic
      projections to the ventral tegmental area.
AB  - Dopaminergic projections to the forebrain arising from the mesencephalic ventral
      tegmentum modulate information processing in cortical and limbic sites. The
      lateral hypothalamus is crucial for the coordination of behavioral responses to
      interoceptive cues. The presence of a hypothalamic input to the ventral tegmental
      area has been known for some time, but the organization of this pathway has
      received little attention. Among the neuropeptides found in the hypothalamus are
      the orexins, which are selectively expressed in the lateral hypothalamus and
      adjacent perifornical area and are critically involved in homeostatic regulatory
      processes, including arousal and feeding. We examined the anatomical
      relationships between orexin and dopamine neurons in rats, with particular
      attention to characterizing the lateral hypothalamic projection to midbrain
      dopamine neurons. Iontophoretic deposits of the retrograde tracer FluoroGold into
      the ventral tegmental area revealed a large number of retrogradely-labeled cells
      that formed a band extending from the medial perifornical area arching dorsally
      over the fornix and then ventrolaterally into the lateral hypothalamus;
      approximately 20% of these cells expressed orexin A-like immunoreactivity.
      Moreover, axons that were anterogradely labeled from the lateral hypothalamus
      were seen throughout the ventral tegmental area, and were often in close
      proximity to the dendrites and somata of dopamine neurons. Dopamine and orexin
      fibers were found to codistribute in the medial prefrontal cortex; orexin fibers
      were present in lower density in the medial shell of the nucleus accumbens, and
      the central and posterior basolateral nuclei of the amygdala. We conclude that
      the lateral hypothalamic/perifornical projection represents an anatomical
      substrate by which interoceptive-related signals may influence forebrain dopamine
      function.

PMID- 11983324
TI  - Different peripheral mechanisms mediate enhanced nociception in metabolic/toxic
      and traumatic painful peripheral neuropathies in the rat.
AB  - Mechanisms underlying neuropathic pain states are poorly understood. We have
      compared mechanisms mediating enhanced nociception of four established models of
      neuropathic pain produced by very different types of insults to the peripheral
      nervous system: streptozotocin-induced hyperalgesia, a model of diabetic
      (metabolic) peripheral neuropathy, vincristine-induced hyperalgesia, a model of
      chemotherapeutic agent (toxic) peripheral neuropathy, and chronic constriction
      injury and partial nerve ligation, models of trauma-induced painful neuropathies.
      All four models resulted in prolonged mechanical hyperalgesia (>30% decrease in
      mechanical nociceptive threshold) and allodynia (detected by 10-209-mN-intensity
      von Frey hairs). In vincristine- and streptozotocin-induced hyperalgesia, the
      protein kinase A, protein kinase C and nitric oxide second messenger pathways in
      the periphery contributed to the hyperalgesia, while N-methyl-D-aspartate (NMDA)
      receptor-mediated events were not detected. None of these second messengers nor
      the NMDA receptor, which can contribute to peripheral sensitization of
      nociceptors, contributed to chronic constriction injury- and partial nerve
      ligation-induced hyperalgesia. In all four models the hyperalgesia was not
      antagonized by peripheral administration of a mu-opioid agonist.Our findings
      support the presence of a common abnormality in second messenger signaling in the
      periphery to the maintenance of two very different models of non-traumatic
      neuropathic pain, not shared by models of trauma-induced neuropathic pain.

PMID- 11983325
TI  - Preservation of neurologic function during inflammatory demyelination correlates
      with axon sparing in a mouse model of multiple sclerosis.
AB  - Axonal injury has been proposed as the basis of permanent deficits in the
      inflammatory, demyelinating disease, multiple sclerosis. However, reports on the
      degree of injury are highly variable, and the responsible mechanisms are poorly
      understood. We examined the relationships among long-term demyelination,
      inflammation, axonal injury, and motor function in a model of multiple sclerosis,
      in which mice develop chronic, immune-mediated demyelination of the spinal cord
      resulting from persistent infection with Theiler's virus. We studied two strains
      of mice, inbred SJL/J and C57BL/6x129 mice deficient in beta(2)-microglobulin and
      therefore CD8 lymphocytes. After 8 months of disease, SJL mice had considerably
      worse motor function than beta(2)-microglobulin-deficient mice. Motor dysfunction
      correlated linearly with the extent of demyelinated lesions in the spinal cord
      (lesion load) within each strain, but no difference in lesion load was present
      between strains. Also, the extent of remyelination did not differ between
      strains. Instead, the disparity in motor deficits reflected differences in the
      integrity of descending neurons. That is, retrograde labeling of reticulospinal,
      vestibulospinal, and rubrospinal neurons, although reduced in all chronically
      diseased mice, was two to seven times higher in beta(2)-microglobulin-deficient
      mice. The labeling was superior in beta(2)-microglobulin-deficient mice despite
      the fact that lesion expanse and therefore the number of axons traversing lesions
      were similar in both strains. Thus, by all criteria axons were equivalently
      demyelinated in SJL and beta(2)-microglobulin-deficient mice, but the extent of
      axonal injury differed significantly. These results indicate that mechanisms of
      demyelination and axonal injury are at least partly separable, and are consistent
      with the hypothesis that cytotoxic CD8 lymphocytes may selectively injure
      demyelinated axons. Additionally, the data suggest that axonal injury
      obligatorily results from chronic inflammatory demyelination and significantly
      contributes to neurological deficits.

PMID- 11983326
TI  - Increase in intracellular Ca(2+) and calcitonin gene-related peptide release
      through metabotropic P2Y receptors in rat dorsal root ganglion neurons.
AB  - We examined the effects of the activation of metabotropic P2Y receptors on the
      intracellular Ca(2+) concentration and the release of neuropeptide calcitonin
      gene-related peptide (CGRP) in isolated adult rat dorsal root ganglion neurons.
      In small-sized dorsal root ganglion neurons (soma diameter<30 microm) loaded with
      fura-2, a bath application of ATP (100 microM) evoked an increase in
      intracellular Ca(2+) concentration, while the removal of extracellular Ca(2+)
      partly depressed the response to ATP, thus suggesting that the ATP-induced
      increase in intracellular Ca(2+) concentration is due to both the release of
      Ca(2+) from intracellular stores and the influx of extracellular Ca(2+). Bath
      application of uridine 5'-triphosphate (UTP; 100 microM) also caused an increase
      in intracellular Ca(2+) concentration in small-sized dorsal root ganglion neurons
      and the P2 receptor antagonists suramin (100 microM) and pyridoxalphosphate-6
      azophenyl-2',4'-disulfonic acid (PPADS; 10 microM) virtually abolished the
      response, indicating that the intracellular Ca(2+) elevation in response to UTP
      is mediated through metabotropic P2Y receptors. This intracellular Ca(2+)
      increase was abolished by pretreating the neurons with thapsigargin (100 nM),
      suggesting that the UTP-induced increase in intracellular Ca(2+) is primarily due
      to the release of Ca(2+) from endoplasmic reticulum Ca(2+) stores. An enzyme
      linked immunosorbent assay showed that an application of UTP (100 microM)
      significantly stimulated the release of CGRP and that suramin (100 microM)
      totally abolished the response, suggesting that P2Y receptor-mediated increase in
      intracellular Ca(2+) is accompanied by CGRP release from dorsal root ganglion
      neurons. These results suggest that metabotropic P2Y receptors contribute to
      extracellular ATP-induced increase in intracellular Ca(2+) concentration and
      subsequent release of neuropeptide CGRP in rat dorsal root ganglion neurons.

PMID- 11983327
TI  - Spinal lamina I neurones that express neurokinin 1 receptors: II.
      Electrophysiological characteristics, responses to primary afferent stimulation
      and effects of a selective mu-opioid receptor agonist.
AB  - Intracellular recordings were made from neurones in laminae I and II of the
      dorsal horn of a longitudinal, parasagittal spinal cord slice from the neonatal
      rat. Their responses to peripheral nerve stimulation were first tested. Then the
      responses to bath application of [Sar(9),Met(O(2))(11)]-substance P and [D
      Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin, neurokinin 1 (NK(1)) and mu-opioid
      receptor agonists respectively, were studied. Finally, the structure of each
      neurone was investigated by injecting neurobiotin intracellularly following
      recording, and immunocytochemical studies were performed on post-fixed tissues to
      reveal whether they expressed the NK(1) receptor. Nine lamina I neurones where
      shown to express NK(1) receptor and these were depolarised by
      [Sar(9),Met(O(2))(11)]-substance P. These neurones typically received a powerful
      C-fibre input that was strongly inhibited, presynaptically, by the mu-opioid
      receptor agonist.The structure, afferent input, opioid sensitivity and intrinsic
      properties of these neurones are all consistent with the view that they are a
      major relay for nociceptive information leading to intense pain. The
      characteristics of 10 other neurones studied in which the NK(1) receptor was not
      found to be expressed at levels detectable by immunocytochemistry are briefly
      described for comparison. These results contribute to the emergent view that the
      large neurones in the most dorsal neuronal layer (lamina I) of the spinal cord,
      which express the principal receptor for substance P (NK(1)) over their entire
      soma and dendrites, are a major relay for information leading to intense pain.
      Inhibition of the relay of information by these neurones would be predicted to
      result in analgesia and hence, a detailed knowledge of their unique neurochemical
      characteristics is of paramount importance.

PMID- 11983328
TI  - Damage control of DNA in nucleosome core particles: when a histone's loving,
      protective embrace is just not good enough.
AB  - Packaging DNA into nucleosome core particles generally offers protection from
      damage by molecules diffusing in solution. However, on page 403 of this issue,
      Barton and coworkers report that although noncovalently bound, activated Rh
      (Rhodium) does not readily bind within nucleosomal DNA, activated Rh that is
      covalently tethered to the 5' terminus of a histone-associated oligonucleotide
      oxidizes guanine bases from a distance of up to 24 base pairs, demonstrating that
      histones do not protect DNA from long-range damage from the transport of charge
      through stacked bases. This implies that oxidative damage generated on DNA in
      vivo may spread from an initially damaged site to distal sites. Once created,
      such sites may persist and be resistant to repair because of the protective
      packaging by histones; they thus may result in permanent mutations.

PMID- 11983329
TI  - Carbohydrate analysis prepares to enter the "Omics" era.
AB  - In this issue, Houseman and Mrksich describe a carbohydrate array preparation
      method that can be used to analyze protein-carbohydrate interactions and to
      characterize the substrate specificity of a carbohydrate-modifying enzyme.
      Carbohydrate chips were prepared by a novel procedure that allows the covalent
      attachment of carbohydrate-diene conjugates to a specially engineered monolayer
      surface. The surface presents a precisely controllable ratio of reactive
      benzoquinone and inert ethylene glycol groups. Nonspecific adsorption of proteins
      to the surface is extremely low, and the surface is compatible with popular
      detection techniques. The immobilization technique was demonstrated to be
      compatible with recently developed automated solid phase carbohydrate synthesis
      methods, paving the way for the development of highly complex carbohydrate
      arrays.

PMID- 11983330
TI  - Oxidative charge transport through DNA in nucleosome core particles.
AB  - Eukaryotic DNA is packaged into nucleosomes, made up of 146 bp of DNA wrapped
      around a core of histone proteins. We used photoexcited rhodium intercalators to
      explore DNA charge transport within these assemblies. Although histone proteins
      inhibit intercalation of the rhodium complex within the core particle, they do
      not prevent 5'-GG-3' oxidation, the signature of oxidative charge transport
      through DNA. Moreover, using rhodium intercalators tethered to the 5' terminus of
      the DNA, we found that guanine bases within the nucleosome can be oxidized from a
      distance of 24 bp. Histone binding did not affect the pattern and extent of this
      oxidation. Therefore, although the structure of the nucleosome core particle
      generally protects DNA from damage by solution-borne molecules, packaging within
      the nucleosome does not protect DNA from charge transfer damage through the base
      pair stack.

PMID- 11983331
TI  - ATP-dependent allosteric DNA enzymes.
AB  - Effector-activated ribozymes that respond to small organic molecules have
      previously been generated by appending binding species (aptamers) to ribozymes.
      In order to determine if deoxyribozymes can similarly be activated by effector
      molecules, we have appended an anti-adenosine aptamer to a selected deoxyribozyme
      ligase. The resultant constructs are specifically activated by ATP. Optimization
      of the joining region resulted in ligases that are activated up to 460-fold by
      ATP. The selected deoxyribozyme catalyzes ligation largely via a templating
      mechanism. Effector activation is surprisingly achieved by suppression of the
      rate of the background, templated ligation reaction in the absence of the
      effector molecule, probably by misalignment of the oligonucleotide substrates.
      This novel allosteric mechanism has not previously been observed for nucleic-acid
      catalysts and is rare even in protein catalysts.

PMID- 11983332
TI  - Differential effects of FR900482 and FK317 on apoptosis, IL-2 gene expression,
      and induction of vascular leak syndrome.
AB  - Vascular leak syndrome (VLS) is a harmful side effect that resulted in withdrawal
      of the antitumor drug FR900482, but not FK317, from clinical trials. Here we
      present chromatin immunoprecipitation data showing that FK317, like FR900482,
      crosslinks minor-groove binding proteins to DNA in vivo. However, these drugs
      differ in how they induce cell death. We demonstrate that, whereas FR900482
      induces necrosis, FK317 induces a necrosis-to-apoptosis switch that is drug
      concentration dependent. Northern blot analyses of drug-treated cells suggest
      that this "switch" is mediated, at least in part, by modulation of the expression
      levels of Bcl-2. Additionally, FR900482, in contrast to FK317, induces the
      expression of known elicitors of both Bcl-2 gene expression and VLS. These
      findings provide plausible explanations for why these structurally similar drugs
      have different biological effects, especially with respect to VLS.

PMID- 11983333
TI  - Carbohydrate arrays for the evaluation of protein binding and enzymatic
      modification.
AB  - This paper reports a chemical strategy for preparing carbohydrate arrays and
      utilizes these arrays for the characterization of carbohydrate-protein
      interactions. Carbohydrate chips were prepared by the Diels-Alder-mediated
      immobilization of carbohydrate-cyclopentadiene conjugates to self-assembled
      monolayers that present benzoquinone and penta(ethylene glycol) groups. Surface
      plasmon resonance spectroscopy showed that lectins bound specifically to
      immobilized carbohydrates and that the glycol groups prevented nonspecific
      protein adsorption. Carbohydrate arrays presenting ten monosaccharides were then
      evaluated by profiling the binding specificities of several lectins. These arrays
      were also used to determine the inhibitory concentrations of soluble
      carbohydrates for lectins and to characterize the substrate specificity of beta
      1,4-galactosyltransferase. Finally, a strategy for preparing arrays with
      carbohydrates generated on solid phase is shown. This surface engineering
      strategy will permit the preparation and evaluation of carbohydrate arrays that
      present diverse and complex structures.

PMID- 11983334
TI  - Aminoglycosides modified by resistance enzymes display diminished binding to the
      bacterial ribosomal aminoacyl-tRNA site.
AB  - Understanding the basic principles that govern RNA binding by aminoglycosides is
      important for the design of new generations of antibiotics that do not suffer
      from the known mechanisms of drug resistance. With this goal in mind, we examined
      the binding of kanamycin A and four derivatives (the products of enzymic
      turnovers of kanamycin A by aminoglycoside-modifying enzymes) to a 27 nucleotide
      RNA representing the bacterial ribosomal A site. Modification of kanamycin A
      functional groups that have been directly implicated in the maintenance of
      specific interactions with RNA led to a decrease in affinity for the target RNA.
      Overall, the products of reactions catalyzed by aminoglycoside resistance enzymes
      exhibit diminished binding to the A site of bacterial 16S rRNA, which correlates
      well with a loss of antibacterial ability in resistant organisms that harbor
      these enzymes.

PMID- 11983335
TI  - Rescue of an abasic hairpin ribozyme by cationic nucleobases: evidence for a
      novel mechanism of RNA catalysis.
AB  - The hairpin ribozyme catalyzes a reversible phosphodiester cleavage reaction. We
      examined the roles of conserved nucleobases in catalysis using an abasic ribozyme
      rescue strategy. Loss of the active site G8 nucleobase reduced the cleavage rate
      constant by 350-fold while loss of A9 and A10 nucleobases reduced activity less
      than 10-fold. Certain heterocyclic amines restored partial activity when provided
      in solution to the variant lacking G8. Heterocyclic amines that were capable of
      rescue shared the exocyclic amine and cyclic amide in common with the Watson
      Crick hydrogen bonding face of guanine. In contrast to the shallow pH dependence
      of unmodified ribozyme activity, rescue activity increased sharply with
      decreasing pH. These results support a novel model for RNA catalysis in which a
      cationic nucleobase contributes electrostatic stabilization to negative charge
      developing in the transition state.

PMID- 11983336
TI  - Inhibition and reversal of myogenic differentiation by purine-based microtubule
      assembly inhibitors.
AB  - Using a muscle cell differentiation screen, we have identified myoseverin from a
      2,6,9-trisubsituted purine library as a purine-based microtubule binding molecule
      [1]. Structure-activity relation studies of myoseverin identify positions N2 and
      N6 to be critical for inhibiting muscle differentiation. Inhibition of
      microtubule polymerization induced the reversion of terminally differentiated
      myotubes to mononucleated cells that were responsive to both growth and
      differentiation conditions, without any observable cytotoxicity. Comparison of
      myoseverin derivatives to taxol, vinblastine, nocodazole, and colchicine identify
      myoseverin's effect as being selectively reversible in addition to lacking the
      cytotoxic effects of these non-purine-based microtubule-disrupting molecules.
      Myoseverin, as a purine-based microtubule inhibitor, reverted terminal muscle
      differentiated cells to a state that was responsive to environmental cues. These
      results suggest that myoseverin may have applications in muscle regeneration and
      stem cell differentiation.

PMID- 11983337
TI  - Factor Va increases the affinity of factor Xa for prothrombin: a binding study
      using a novel photoactivable thiol-specific fluorescent probe.
AB  - The multiprotein complex of factor Xa, factor Va, and prothrombin efficiently
      generates the blood-clotting agent, thrombin. Here, the formation of the factor
      Xa*prothrombin complex and the effects of factor Va on this complex were examined
      using a photoactivable thiol-specific fluorescent probe (LWB), which was
      synthesized and incorporated into the active site of factor Xa. The use of
      fluorescent LWB illustrated that factor Xa has an increased affinity for
      prothrombin in the presence of factor Va. Further exposure of these components to
      UV light resulted in a specific photocrosslinking of LWB-factor Xa to
      prothrombin, suggesting a physical association between these proteins. These data
      demonstrate that LWB can successfully function both as a spectroscopic probe and
      as a photocrosslinking reagent for studying protein-protein interactions.

PMID- 11983338
TI  - Rapid identification of small binding motifs with high-throughput phage display:
      discovery of peptidic antagonists of IGF-1 function.
AB  - A panel of 22 naive peptide libraries was constructed in a polyvalent phage
      display format and sorted against insulin-like growth factor-1 (IGF-1). The
      libraries were pooled to achieve a total diversity of 4.4 x 10(11). After three
      rounds of selection, the majority of the phage clones bound specifically to IGF
      1, with a disulfide-constrained CX(9)C scaffold dominating the selection. Four
      monovalently displayed sub-libraries were designed on the basis of these
      conserved motifs. Sub-library maturation in a monovalent format yielded an
      antagonistic peptide that inhibited the interactions between IGF-1 and two cell
      surface receptors and those between IGF-1 and two soluble IGF binding proteins
      with micromolar potency. NMR analysis revealed that the peptide is highly
      structured in the absence of IGF-1, and peptides that preorganize the binding
      elements were selected during the sorting.

PMID- 11983339
TI  - Sequence diversity, metal specificity, and catalytic proficiency of metal
      dependent phosphorylating DNA enzymes.
AB  - Although DNA has not been found responsible for biological catalysis, many
      artificial DNA enzymes have been created by "in vitro selection." Here we
      describe a new selection approach to assess the influence of four common divalent
      metal ions (Ca(2+), Cu(2+), Mg(2+), and Mn(2+)) on sequence diversity, metal
      specificity, and catalytic proficiency of self-phosphorylating deoxyribozymes.
      Numerous autocatalytic DNA sequences were isolated, a majority of which were
      selected using Cu(2+) or Mn(2+) as the divalent metal cofactor. We found that
      Cu(2+)- and Mn(2+)-derived deoxyribozymes were strictly metal specific, while
      those selected by Ca(2+) and Mg(2+) were less specific. Further optimization by
      in vitro evolution resulted in a Mn(2+)-dependent deoxyribozyme with a k(cat) of
      2.8 min(-1). Our findings suggest that DNA has sufficient structural diversity to
      facilitate efficient catalysis using a broad scope of metal cofactor utilizing
      mechanisms.

PMID- 11983340
TI  - The biosynthetic gene cluster for the antitumor rebeccamycin: characterization
      and generation of indolocarbazole derivatives.
AB  - Rebeccamycin, a halogenated natural product of the indolocarbazole family, is
      produced by Saccharothrix aerocolonigenes ATCC39243. Several rebeccamycin
      analogues, which target DNA topoisomerase I or II, have already entered clinical
      trials as anticancer drugs. Using as a probe an internal fragment of ngt, a
      Saccharothrix aerocolonigenes gene encoding an indolocarbazole N
      glycosyltransferase, we isolated a DNA region that directed the biosynthesis of
      rebeccamycin when introduced into Streptomyces albus. Sequence analysis of 25.6
      kb revealed genes for indolocarbazole core formation, halogenation,
      glycosylation, and sugar methylation, as well as a regulatory gene and two
      resistance/secretion genes. Heterologous expression of subsets of these genes
      resulted in production of deschloro-rebeccamycin, 4'-demethyldeschloro
      rebeccamycin, and deschloro-rebeccamycin aglycone. The cloned genes should help
      to elucidate the molecular basis for indolocarbazole biosynthesis and set the
      stage for the generation of novel indolocarbazole analogues by genetic
      engineering.

PMID- 11983341
TI  - Molecular diagnosis of familial adenomatous polyposis (FAP): genotyping of
      adenomatous polyposis coli (APC) alleles by MALDI-TOF mass spectrometry.
AB  - OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal dominantly
      inherited colorectal cancer predisposition syndrome caused by germ line mutations
      in the adenomatous polyposis coli gene (APC). For prophylactic colectomy, timely
      identification of patients at risk is urgent. Here, matrix assisted laser
      desorption ionization - time of flight - mass spectrometry (MALDI-TOF-MS)
      genotyping is offered for an efficient molecular diagnosis of APC germline
      mutations. DESIGN AND METHODS: The four most frequent APC germ line mutations
      (three deletions, one point mutation) were genotyped by allele specific
      elongation and termination of extension primers. The extension products generated
      were analyzed by MALDI-TOF-MS. RESULTS: Following PCR amplification and allele
      specific primer extension reactions MALDI-TOF-MS allowed the unambiguous
      identification of informative nucleic acid fragments corresponding to distinct
      genotypes or mutants even in duplex assays. Results were confirmed by DNA
      sequencing. CONCLUSIONS: Due to its high molecular resolution and accuracy, this
      method is highly suitable as an alternative for clinical APC genotyping.

PMID- 11983342
TI  - Protein kinases activities in erythrocyte membranes of asphyxiated newborns.
AB  - OBJECTIVES: Perinatal asphyxia represents a major cause of acute brain impairment
      and mortality in neonates. To develop the effective therapies able to reduce post
      asphyxial damages, the understanding of biochemical processes accompanying
      asphyxia appears to be of the great relevance. DESIGN AND METHODS: The activities
      of protein kinases A and C, and tyrosine kinases in erythrocyte membranes of
      healthy and asphyxiated neonatals were compared. Using monoclonal antibodies the
      band 3 presence and its phosphotyrosine levels were assayed. RESULTS: In
      asphyxiated erythrocyte membranes the activities of PKA and tyrosine kinases
      increased, whereas the activity of PKC was reduced in relation to healthy
      newborns. Under asphyxia the band 3 has been overphosphorylated; however, its
      amount decreased. CONCLUSION: These findings may provide some evidence for a
      potential role of asphyxia in disturbance of phosphorylation processes in
      erythrocytes, as reflected by altered protein kinases activities. The diminished
      band 3 presence may be partially responsible for the impairment of erythrocyte
      function.

PMID- 11983343
TI  - Simple rapid method for quantification of antiretrovirals by liquid
      chromatography-tandem mass-spectrometry.
AB  - OBJECTIVES: The aim of the current study was to develop a simple, fast and
      universal method for quantification of any combination of all currently marketed
      anti-HIV drugs in human plasma, using a LC-tandem mass spectrometer (API-2000,
      SCIEX, Toronto, Canada). METHODS: 80 microL plasma were spiked with internal
      standard (cimetidine), and protein precipitated with 200 microL acetonitrile. The
      sample was centrifuged and 30 microL aliquot was injected onto the HPLC column,
      where it underwent an online extraction with ammonium acetate. After that the
      automatic switching valve was activated, changing the mobile phase to methanol
      and thereby eluting the analytes into the tandem mass spectrometer. Stavudine,
      AZT and efavirenz were analyzed in the negative MS/MS mode, while all other drugs
      were analyzed in the positive mode. The high selectivity of a tandem mass
      analyzer allows determination of any combination of the drugs within a 4.5 min
      run. RESULTS: Between-day precision was below 10% for all analytes at the
      concentrations tested. Accuracy ranged between 95% and 105% (n = 20). The method
      was linear over the measuring ranges of all analytes. Within-run precision gave a
      CV < 7% for all analytes. Good correlation with other analytical methods was
      observed. CONCLUSIONS: The simplicity, universality and high throughput of the
      method make it suitable for application in a clinical laboratory. The method has
      been implemented in our laboratory for routine use.

PMID- 11983344
TI  - Clinical utility of a rapid test for uristatin.
AB  - OBJECTIVES: Uristatin is a trypsin inhibitor present in urine that is increased
      in most patients with bacterial or viral infections and in many with inflammatory
      disorders. We included the assay of uristatin as part of a screening program
      carried out by pediatricians on 4207 Japanese schoolchildren to judge the ability
      of uristatin to identify those with an infection and (or) inflammation of any
      cause. We used urine dipsticks for the assay of uristatin, creatinine, albumin,
      blood, leukocyte esterase, and protein. We also performed quantitative assays for
      uristatin and creatinine. Another aim was to estimate the reference range for
      uristatin in schoolchildren, ages 5 to 14 yr. METHODS: We prepared dipstick pads
      that were impregnated with a chromogenic substrate for trypsin and measured the
      uristatin-caused inhibition of trypsin in urine. We measured creatinine so that
      the ratio of uristatin to creatinine could be calculated to correct for urine
      concentration. RESULTS: We obtained quantitative uristatin and creatinine results
      for 4207 children. Of these, 177 had an abnormal urine dipstick for albumin or
      blood or protein or leukocyte esterase or a combination of these. We used data
      from 3622 children to establish the reference range for the uristatin dipsticks.
      The 3622 were diagnosed by their pediatricians as free from an infection or
      inflammation of any cause and with normal urine dipstick tests. We recommend an
      upper reference limit for uristatin by dipstick of < or = 7.5 mg uristatin/g
      creatinine. The leftover 408 children ( [4207-3622-177] = 408) fell into two
      groups: 205 with diagnoses of no infection, possible infection, or possible
      inflammatory disorders. The remaining 203 children were renal disease follow-up
      cases. The diagnoses were based on a physical examination, microscopic urinalysis
      plus urine dipstick tests for albumin, blood, creatinine, protein, leukocyte
      esterase and a complete blood count. In the 205 children, 46 had an abnormal
      uristatin dipstick test, 39 had an abnormal uristatin by immunoassay, 41 had an
      abnormal erythrocyte sedimentation rate (ESR), 27 had an abnormal serum C
      reactive protein (CRP), and one had an abnormal urine microscopic exam. For the
      first 938 children in the study, the agreement was 93% of negative dipstick
      uristatin results and immunoassays. The agreement of positive uristatin dipsticks
      with immunoassays was 85%. We assumed that the immunoassay results were correct.
      In the evaluation of 189 children with fever, 62 also had an abnormal uristatin
      by dipstick. DISCUSSION: A rapid dipstick test for uristatin read on a
      reflectance photometer gave values that compared well with a quantitative
      immunoassay method. The uristatin test is sensitive but not specific for any
      cause of infection or inflammation. Uristatin is easy to determine and appears to
      be a better indicator than fever, ESR, or CRP for the diagnosis of an infection
      or inflammation.

PMID- 11983345
TI  - Determination of cardiac troponin I forms in the blood of patients with unstable
      angina pectoris.
AB  - OBJECTIVE: To determine the predominant form in which cardiac troponin I
      circulates in the bloodstream of unstable angina patients. DESIGN AND METHODS:
      The cardiac troponin I forms released in the bloodstream of 25 patients suffering
      from unstable angina were examined by using three immunoenzymatic assays: the
      total cTnI assay for detection of free and complexed cTnI, the IC-TIC assay for
      detection of the IC and TIC troponin complexes, and the IT-TIC assay for
      detection of the IT and TIC troponin complexes. RESULTS: Approximately 60% of
      patients with unstable angina had at least one positive value in the total cTnI
      assay or in the IC-TIC assay. Our results demonstrated that the predominant
      cardiac troponin I form circulating in the bloodstream of patients with unstable
      angina was the IC complex. Free cTnI, IT, and/or TIC forms were seldom found, the
      frequency of IT and/or TIC complexes being higher than that observed previously
      in patients with acute myocardial infarction. CONCLUSIONS: The release pattern of
      cTnI in patients suffering from unstable angina is similar to that previously
      observed in patients with acute myocardial infarction, i.e., a predominance of
      the IC complex.

PMID- 11983346
TI  - A comparison of the anticarcinogenic properties of four red wine polyphenols.
AB  - BACKGROUND: There has been growing interest in the analysis of certain
      polyphenols in wine, especially flavonoids, trihydroxystilbenes and phenolic
      acids, stimulated by intense research into their potential benefits to human
      health. One of their main properties in this regard is their antioxidant
      activity, which enables them to attenuate the development of atherosclerosis,
      inflammatory diseases, and cancer. METHODS: A two stage CD-1 mouse skin cancer
      model using 9,10-dimethyl-1,2-benzanthracene (DMBA) as initiator and phorbol 12
      myristate 13-acetate (TPA) as promoter was employed to compare the
      antitumorigenic activities of one polyphenol from each of four different classes:
      flavanols [(+)-catechin], stilbenes (trans-resveratrol), flavonols (quercetin)
      and hydroxybenzoic acids (gallic acid). Animals were treated with specific
      polyphenols at doses ranging from 0 to 25 micromoles (dissolved in 200 microL
      acetone), twice a week for eighteen weeks. The solution was applied topically to
      the shaved dorsal region of each animal. The relative potencies of the
      polyphenols were compared by evaluating the percentage inhibition of tumor
      formation in individual mice and the number of mice developing one or more tumors
      with the different dose schedules. RESULTS: Probit analysis revealed that
      quercetin was the most (ED(50)<1 micromole) and gallic acid the least effective
      (ED(50) 5-10 micromoles). (+)-Catechin and trans-resveratrol were intermediate,
      with ED(50) values of 5 and 6 micromoles, respectively. CONCLUSION: We have shown
      recently that trans-resveratrol is absorbed much more efficiently than (+)
      catechin and quercetin in humans after oral consumption. Taking this and the
      relative concentrations in red wine into account, together with the present
      results, we conclude that trans-resveratrol may be the most effective anticancer
      polyphenol present in red wine as consumed po by healthy human subjects.

PMID- 11983347
TI  - Successful pregnancy outcome in a patient with severe chylomicronemia due to
      compound heterozygosity for mutant lipoprotein lipase.
AB  - OBJECTIVES: Familial chylomicronemia syndrome is characterized by massive
      accumulation of plasma chylomicrons, which typically results from an absolute
      deficiency of lipoprotein lipase (LPL). Chylomicronemia in pregnancy is a rare,
      but serious clinical problem and can be found in patients with underlying
      molecular defects in the LPL gene. We report the course and treatment of an 18 yr
      old primigravida who had LPL deficiency and hypertriglyceridemia since birth. We
      also analyzed the molecular basis of her LPL deficiency. DESIGN AND METHODS: The
      patient's antenatal course was complicated by extreme elevations of plasma
      triglycerides. Her management included a very low fat diet, pharmacotherapy with
      gemfibrozil in the third trimester, and intermittent hospitalization with periods
      of fasting supplemented by IV glucose feeding. We used DNA sequencing to
      determine whether mutations in LPL were present. RESULTS: At 38 weeks of
      gestation, labor was induced, and the patient delivered a healthy 2.77 kilogram
      male. Postnatal triglycerides fell to prenatal levels. DNA sequencing showed that
      she was a compound heterozygote for mutant LPL: I > T194 and R > H243.
      CONCLUSIONS: This experience indicates that vigilance is required during
      pregnancy in patients with familial chylomicronemia due to mutant LPL.
      Gemfibrozil was used in this patient without apparent adverse effects. Compound
      heterozygosity for LPL mutations is an important underlying mechanism for LPL
      deficiency.

PMID- 11983349
TI  - Clinical importance of erythrocyte malondialdehyde levels as a marker for
      cognitive deterioration in patients with dementia of Alzheimer type: a repeated
      study in 5-year interval.
AB  - OBJECTIVES: The aim of the present study was to determine the effects of aging
      and dementia of the Alzheimer type (DAT) on lipid peroxidation and antioxidant
      enzyme activities. DESIGN AND METHODS: Twenty-six patients with DAT were included
      in the present study. Group I: 26 patients diagnosed as DAT and studied 5 yr ago.
      Group II: This group consisted of the same patients as Group I at the present
      time. Activities of CuZn superoxide dismutase (CuZn SOD) and glutathione
      peroxidase (GSH-Px) and malondialdehyde (MDA) concentrations of these 26 subjects
      were measured and mini mental state examination (MMSE), brief psychiatric rating
      scale (BPRS), Hamilton depression rating scale (HDRS) were applied. RESULTS: The
      results revealed that 26 dementia patients had worsened cognitive symptoms and
      significantly increased CuZn SOD and MDA levels and decreased GSH-Px levels after
      5 yr. Significant correlation was found between age and CuZn SOD (r: +0.406, p:
      0.034), and between MMSE and MDA (r: -0.411, p: 0.032). CONCLUSIONS: We can
      conclude that MDA, CuZn SOD, and GSH-Px were significantly affected in the
      patients with Alzheimer disease. The most striking finding of this study is the
      significant correlation between MMSE and MDA in patients with DAT.

PMID- 11983348
TI  - Newborn thyroxine levels and childhood ADHD.
AB  - OBJECTIVES: Normal brain development is highly dependent on adequate levels of
      iodine and thyroid hormone. It has been suggested that Attention Deficit
      Hyperactivity Disorder (ADHD) is the consequence of prenatal thyroidal endocrine
      disruption. The hypothesis was examined using neonatal thyroxine levels as a bio
      marker of prenatal thyroid status and comparing it to subsequent development of
      ADHD. DESIGN AND METHODS: In a matched case-control study, cases were defined as
      children diagnosed with ADHD, while children born in the same hospital and tested
      on the same day served as matched controls. Conditional logistic regression
      analysis with unequal numbers of controls was performed. RESULTS: The neonatal
      thyroxine levels were within normal limits for each of the children who were
      subsequently diagnosed as having ADHD, and their distribution was no different
      from that of their controls. CONCLUSIONS: Children diagnosed with ADHD do not
      demonstrate prenatal thyroidal dysfunction as reflected in the newborn thyroxine
      levels, therefore neonatal thyroxine levels are not a bio-marker for the
      subsequent development of ADHD.

PMID- 11983350
TI  - Analytical performance of the Roche total and free PSA assays on the Elecsys 2010
      immunoanalyzer.

PMID- 11983351
TI  - Changes in antioxidant status of lung tissue in experimental diabetes in rabbits.
AB  - OBJECTIVES: Hyperglycaemia can result in oxidative stress which may affected as
      cellular tissue damage. DESIGN AND METHODS: After 3, 6, 12 and 24 weeks of
      hyperglycaemia oxidative stress related parameters were measured in lung tissue
      of diabetic and control rabbits. RESULTS: Decreased activities of antioxidative
      compounds and intensification of lipid peroxidation process were found in
      diabetic lung. CONCLUSIONS: The data obtained suggest that hyperglycaemia induces
      oxidative stress in lung tissue which may play an important role in pathogenesis
      of diabetic complications.

PMID- 11983383
TI  - High pressure effects on biological macromolecules: from structural changes to
      alteration of cellular processes.

PMID- 11983384
TI  - Pressure-temperature phase diagrams of biomolecules.
AB  - The pressure-temperature phase diagram of various biomolecules is reviewed.
      Special attention is focused on the elliptic phase diagram of proteins. The
      phenomenological thermodynamic theory describing this diagram explains the heat,
      cold and pressure denaturations in a unified picture. The limitations and
      possible developments of this theory are discussed as well. It is pointed out
      that a more complex diagram can be obtained when the intermolecular interactions
      are also taken into account. In this case metastable states appear on the
      pressure-temperature (p-T) diagram due to intermolecular interactions. Pressure
      temperature phase diagrams of other biopolymers are also discussed. While the p-T
      diagrams of helix-coil transition of nucleic acids and of gel-liquid crystal
      transition of lipid bilayers are non-elliptical, those of gelatinization of
      starch and of phase separation of some synthetic polymers show an elliptic
      profile, similar to that of proteins. Finally, the p-T diagram of bacterial
      inactivation is shown to be elliptic. From the point of view of basic science,
      this fact shows that the key factor of inactivation should be the protein type,
      and from the viewpoint of practical applications, it serves as the theoretical
      basis of pressure treatment of biosystems.

PMID- 11983385
TI  - The effects of osmotic and hydrostatic pressures on macromolecular systems.
AB  - Osmotic pressure and hydrostatic pressure can be used effectively to probe the
      behavior of biologically important macromolecules and their complexes. Using the
      two techniques requires a theoretical framework as well as knowledge of the more
      common pitfalls. Both are discussed in this review in the context of several
      examples.

PMID- 11983386
TI  - Compressibility of protein transitions.
AB  - We review the results of compressibility studies on proteins and low molecular
      weight compounds that model the hydration properties of these biopolymers. In
      particular, we present an analysis of compressibility changes accompanying
      conformational transitions of globular proteins. This analysis, in conjunction
      with experimental compressibility data on protein transitions, were used to
      define the changes in the hydration properties and intrinsic packing associated
      with native-to-molten globule, native-to-partially unfolded, and native-to-fully
      unfolded transitions of globular proteins. In addition, we discuss the molecular
      origins of predominantly positive changes in compressibility observed for
      pressure-induced denaturation transitions of globular proteins. Throughout this
      review, we emphasize the importance of compressibility data for characterizing
      protein transitions, while also describing how such data can be interpreted to
      gain insight into role that hydration and intrinsic packing play in modulating
      the stability of and recognition between proteins and other biologically
      important compounds.

PMID- 11983387
TI  - Effects of high pressure on enzymatic activity.
AB  - Effects of high pressure on enzymatic reactions are poised to revolutionize
      enzyme kinetics. The reason for this is that experimental designs are at hand to
      separate effects on equilibria between reactant states from effects on catalytic
      transition states and both yield new information. The first of the former runs
      contrary to Pauling's hypothesis that substrates are bound more tightly in the
      transition state, while the latter penetrates the 'black box' of catalysis, the
      stabilized transition state itself, and returns a precise measure of a physical
      parameter, deltaV. This in turn opens the door to new forms of structure-activity
      relationships. The first of these has been described, the effect of pressure on
      isotope effects, with the surprising finding that the entire isotope effect comes
      from a transition state phenomenon such as quantum mechanical hydrogen tunneling.

PMID- 11983388
TI  - UV-visible derivative spectroscopy under high pressure.
AB  - High hydrostatic pressure affects proteins, changing their intra- or
      intermolecular interactions, conformation and solvation. How to detect these
      changes? In this paper, via some selected examples, we show the potentiality (but
      also the limits) of the ultraviolet derivative spectroscopy specially adapted to
      high pressure experiments.

PMID- 11983389
TI  - High pressure static fluorescence to study macromolecular structure-function.
AB  - Through some typical examples, the high pressure static fluorescence method is
      described. The potentiality of the intrinsic and extrinsic fluorescence probes
      are analyzed for structural characterizations. Special attention is given to the
      use of fluorescence to understand the behavior of enzymatic reactions under high
      pressure. The application of fluorescence polarization is also presented together
      with some relevant spectroscopic problems inherent in data interpretation.

PMID- 11983390
TI  - Investigation of the effect of high hydrostatic pressure on proteins and lipidic
      membranes by dynamic fluorescence spectroscopy.
AB  - Dynamic fluorescence spectroscopy brings new insight into the functional and
      structural changes of biological molecules under moderate and high hydrostatic
      pressure. The principles of time-resolved fluorescence methods are briefly
      described and the resulting type of information is summarized. A first set of
      selected applications of the use of dynamic fluorescence on pressure effects on
      proteins in terms of denaturation, ternary and quaternary structure, aggregation
      and also interaction with DNA are presented. A second set of applications is
      devoted to the effect of pressure and of cholesterol on lateral heterogeneity of
      lipidic membranes.

PMID- 11983391
TI  - Tryptophan phosphorescence and pressure effects on protein structure.
AB  - After a brief introduction of the potentialities of Trp phosphorescence
      spectroscopy for probing the conformation and flexibility of protein structure,
      this presentation summarizes the effects of hydrostatic pressure (up to 3 kbar)
      on the native fold of monomeric and oligomeric proteins as inferred from the
      variation of the intrinsic phosphorescence lifetime and the oxygen and acrylamide
      bimolecular quenching rate constants of buried Trp residues. The
      pressure/temperature response of the globular fold and modulation of its
      dynamical structure is analyzed both in terms of a reduction of internal cavities
      and of hydration of the polypeptide. The implications of these findings for the
      thermodynamic stability of proteins and for the determination of subunit
      dissociation equilibria under high pressure conditions are also discussed.

PMID- 11983392
TI  - Fourier transform infrared spectroscopy in high-pressure studies on proteins.
AB  - Several aspects of the application of Fourier transform infrared spectroscopy
      (FTIR) in high-pressure studies on proteins are reviewed. Basic methodological
      considerations regarding spectral band assignments, quantitative analysis, and
      choice of pressure calibrants are also placed within the scope of this paper.
      This work attempts to evaluate recent developments in the field of high-pressure
      FTIR of proteins and its prospects for future. Particular attention is paid to
      the phenomenon of protein aggregation.

PMID- 11983393
TI  - High-resolution nuclear magnetic resonance studies of proteins.
AB  - The combination of advanced high-resolution nuclear magnetic resonance (NMR)
      techniques with high-pressure capability represents a powerful experimental tool
      in studies of protein folding. This review is organized as follows: after a
      general introduction of high-pressure, high-resolution NMR spectroscopy of
      proteins, the experimental part deals with instrumentation. The main section of
      the review is devoted to NMR studies of reversible pressure unfolding of proteins
      with special emphasis on pressure-assisted cold denaturation and the detection of
      folding intermediates. Recent studies investigating local perturbations in
      proteins and the experiments following the effects of point mutations on pressure
      stability of proteins are also discussed. Ribonuclease A, lysozyme, ubiquitin,
      apomyoglobin, alpha-lactalbumin and troponin C were the model proteins
      investigated.

PMID- 11983394
TI  - Synchrotron X-ray and neutron small-angle scattering of lyotropic lipid
      mesophases, model biomembranes and proteins in solution at high pressure.
AB  - In this review we discuss the use of X-ray and neutron diffraction methods for
      investigating the temperature- and pressure-dependent structure and phase
      behaviour of lipid and model biomembrane systems. Hydrostatic pressure has been
      used as a physical parameter for studying the stability and energetics of lipid
      mesophases, but also because high pressure is an important feature of certain
      natural membrane environments and because the high pressure phase behaviour of
      biomolecules is of importance for several biotechnological processes. Using the
      pressure jump relaxation technique in combination with time-resolved synchrotron
      X-ray diffraction, the kinetics of different lipid phase transformations was
      investigated. The techniques can also be applied to the study of other soft
      matter and biomolecular phase transformations, such as surfactant phase
      transitions and protein un/refolding reactions. Several examples are given. In
      particular, we present data on the pressure-induced unfolding and refolding of
      small proteins, such as Snase. The data are compared with the corresponding
      results obtained using other trigger mechanisms and are discussed in the light of
      recent theoretical approaches.

PMID- 11983395
TI  - High pressure simulations of biomolecules.
AB  - Pressure is a thermodynamic variable which is particularly suitable for
      exploration of the properties of biological macromolecules. For proteins, in
      particular, denaturation induced by pressure is different from that induced by
      temperature or denaturants. The response of proteins to pressure changes can
      provide information on properties of their native and non-native states. This
      review focuses on molecular dynamics studies of the effect of pressure on
      detailed atomic models of proteins. It also reports on other theoretical
      approaches, such as Monte Carlo simulations, which have been used to study
      simplified models. Another purpose of this review is to try to point out
      potential future studies that may be both interesting and feasible, with
      constantly increasing computing power.

PMID- 11983396
TI  - Revisiting volume changes in pressure-induced protein unfolding.
AB  - It has long been known that the application of hydrostatic pressure generally
      leads to the unfolding of proteins. Despite a relatively large number of reports
      in the literature over the past few decades, there has been great confusion over
      the sign and magnitude as well as the fundamental factors contributing to volume
      effects in protein conformational transitions. It is the goal of this review to
      present and discuss the results obtained concerning the sign and magnitude of the
      volume changes accompanying the unfolding of proteins. The vast majority of cases
      point to a significant decrease in volume upon unfolding. Nonetheless, there is
      evidence that, due to differences in the thermal expansivity of the folded and
      unfolded states of proteins reported in a half dozen manuscripts, that the sign
      of the volume change may become positive at higher temperatures.

PMID- 11983397
TI  - Expanding the pressure technique: insights into protein folding from combined use
      of pressure and chemical denaturants.
AB  - The fundamental principles derived from in vitro protein folding experiments have
      practical application in understanding the pathology of diseases of protein
      misfolding and for the development of industrial processes to produce proteins as
      pharmaceuticals and biotechnological reagents. High pressure as a tool to
      denature or disaggregate proteins offers a number of unique advantages. The
      emphasis of this review is on how low concentrations of chemical denaturants can
      be used in combination with high pressure to extend the range and scope of this
      useful technique. This approach has already been used in a number of studies,
      which are discussed here in the context of the questions they address. These
      include: the origin of the volume change observed on protein unfolding, pressure
      induced formation of partially structured intermediates, pressure-induced
      dissociation of oligomeric and aggregated proteins, and the use of volume changes
      to probe the structure of the transition state. Wider use of hydrostatic pressure
      as a denaturation tool, facilitated by combination with chemical denaturants, is
      likely to bring significant advances to our understanding of protein structure,
      stability and folding, particularly in relation to proteins associated with the
      amyloid and prion diseases.

PMID- 11983398
TI  - High hydrostatic pressure as a tool to study protein aggregation and amyloidosis.
AB  - Aggregation of proteins is a serious problem, affecting both industrial
      production of proteins and human health. Despite recent advances in the theories
      and experimental techniques available to address understanding of protein
      aggregation processes, mechanisms of aggregate formation have proved challenging
      to study. This is in part because the typical irreversibility of protein
      aggregation processes at atmospheric conditions complicates analysis of their
      kinetics and thermodynamics. Because high hydrostatic pressures act to disfavor
      the hydrophobic and electrostatic interactions that cause protein aggregation,
      studies conducted under high hydrostatic pressures may allow protein aggregates
      to be formed reversibly, enabling thermodynamic and kinetic parameters to be
      measured in greater detail. Although application of high hydrostatic pressures to
      protein aggregation problems is rather recent, a growing literature, reviewed
      herein, suggests that high pressure may be a useful tool for both understanding
      protein aggregation and reversing it in industrial applications.

PMID- 11983399
TI  - Pressure effects on intra- and intermolecular interactions within proteins.
AB  - The effects of pressure on protein structure and function can vary dramatically
      depending on the magnitude of the pressure, the reaction mechanism (in the case
      of enzymes), and the overall balance of forces responsible for maintaining the
      protein's structure. Interactions between the protein and solvent are also
      critical in determining the response of a protein to pressure. Pressure has long
      been recognized as a potential denaturant of proteins, often promoting the
      disruption of multimeric proteins, but recently examples of pressure-induced
      stabilization have also been reported. These global effects can be explained in
      terms of pressure effects on individual molecular interactions within proteins,
      including hydrophobic, electrostatic, and van der Waals interactions, which can
      now be studied in greater detail than ever before. However, many uncertainties
      remain, and thorough descriptions of how proteins respond to pressure remain
      elusive. This review summarizes basic concepts and new findings related to
      pressure effects on intra- and intermolecular interactions within proteins and
      protein complexes, and discusses their implications for protein structure
      function relationships under pressure.

PMID- 11983400
TI  - Pressure induces folding intermediates that are crucial for protein-DNA
      recognition and virus assembly.
AB  - Protein-nucleic acid interactions are crucial for a variety of fundamental
      biological processes such as replication, transcription, restriction, translation
      and virus assembly. The molecular basis of protein-DNA and protein-RNA
      recognition is deeply related to the thermodynamics of the systems. We review
      here how protein-nucleic acid interactions can be approached in the same way as
      protein-protein interactions involved in protein folding and protein assembly,
      using hydrostatic pressure as the primary tool and employing several
      spectroscopic techniques, especially fluorescence, circular dichroism and high
      resolution nuclear magnetic resonance. High pressure has the unique property of
      stabilizing partially folded states or molten-globule states of a protein. The
      competition between correct folding and misfolding, which in many proteins leads
      to formation of insoluble aggregates is an important problem in the biotechnology
      industry and in human diseases such as amyloidosis, Alzheimer's, prion and tumor
      diseases. The pressure studies reveal that a gradient of partially folded (molten
      globule) conformations is present between the unfolded and fully folded structure
      of several bacteria, plant and mammalian viruses. Using pressure, we have
      detected the presence of a ribonucleoprotein intermediate, where the coat protein
      is partially unfolded but bound to RNA. These intermediates are potential targets
      for antiviral compounds. Pressure studies on viruses have direct biotechnological
      applications. The ability of pressure to inactivate viruses has been evaluated
      with a view toward the applications of vaccine development and virus
      sterilization. Recent studies demonstrate that pressure causes virus inactivation
      while preserving the immunogenic properties. There is substantial evidence that a
      high-pressure cycle traps a virus in the 'fusion intermediate state', not
      infectious but highly immunogenic.

PMID- 11983401
TI  - The interactions of nucleic acids at elevated hydrostatic pressure.
AB  - The application of elevated hydrostatic pressure on the order of a few thousand
      bar provides insight into the molecular forces responsible for stabilizing the
      conformations and non-covalent interactions of biological molecules in aqueous
      solution. In particular, the parameters derived from these studies have enabled
      researchers to glean information regarding the importance of hydration in the
      energetics and kinetics of these systems. This review presents data concerned
      with the application of hydrostatic pressure to study the thermodynamics,
      kinetics, and structure of nucleic acids and the interactions between nucleic
      acids and proteins, enzymes, and drugs. These complexes often form extremely
      stable non-covalent complexes in which electrostatic interactions play an
      important role. The sensitivity of these interactions to pressure offers a
      valuable experimental tool for investigating the energetics of the complexes.

PMID- 11983402
TI  - Experimental and theoretical high pressure strategies for investigating protein
      nucleic acid assemblies.
AB  - A method was developed to investigate the stability of protein-nucleic acid
      complexes using hydrostatic pressure during electrophoretic gel mobility shift
      analysis. The initial system probed by this technique was the well-characterized
      cognate BamHI-DNA complex. Band shift analysis at several elevated pressures
      found the equilibrium dissociation (K(d)) constant to be dependent on pressure,
      which allowed the volume change of dissociation (deltaV) to be calculated. In
      order to describe the effects of pressure on the specific BamHI-DNA complex at
      the molecular level, molecular dynamics simulations at both ambient and elevated
      pressure was performed. Comparison of the simulation trajectories identified
      several individual BamHI-DNA contacts that are disrupted due to pressure. The
      disruption of these contacts can be attributed to an observed pressure-induced
      increase in hydration at the protein-DNA interface during the elevated pressure
      simulation.

PMID- 11983403
TI  - Effect of pressure on electron transfer reactions in inorganic and bioinorganic
      chemistry.
AB  - Kinetic and thermodynamic studies involving the application of different high
      pressure techniques, are very useful in gaining mechanistic information on the
      basis of volume changes that occur during inorganic and bioinorganic electron
      transfer reactions. The most fundamental type of electron transfer reaction
      concerns self-exchange reactions, for which the overall reaction volume is zero,
      and activation volumes can be measured and discussed. In the case of non
      symmetrical electron transfer reactions, intra- and intermolecular processes can
      be studied and volume profiles can be constructed. Precursor complex formation
      can in some cases be recognized kinetically in such systems. Typical values of
      activation and reaction volumes are reviewed for various reversible and
      irreversible electron transfer reactions. Mechanistic conclusions reached on the
      basis of these parameters are presented. Volume profiles for electron transfer
      reactions enable a simplistic presentation of the reaction mechanism on the basis
      of intrinsic and solvational volume changes along the reaction coordinate.

PMID- 11983404
TI  - High pressure, a tool for exploring heme protein active sites.
AB  - High pressure is an interesting and suitable parameter in the study of the
      dynamics and stability of proteins. The effects of pressure on proteins
      delineates its volumic (deltaV degrees ) and energetic (deltaG degrees )
      parameters. An enormous amount of effort has been invested by several
      laboratories in developing basic theory and high pressure techniques that allow
      the determination of barotropic parameters. Cytochrome P450s, one of the largest
      super families of heme proteins, are good models for high pressure studies. Two
      distinct pressure-induced spin transitions of the heme iron in the active site
      and a P450 to P420 inactivation process have been characterized. The obtained
      reaction volumes of these two processes for a series of analog-bound cytochrome
      P450s are compared. We have shown that both the spin volume and the inactivation
      volume are dependent on the substrate analogs which are known to modulate the
      polarity and hydration of the heme pocket. Several linear correlations were found
      between these reaction volumes and the physico-chemical properties of the heme
      protein such as the polarity-induced exposure of tyrosines, the hydration of the
      cytochrome CYP101 heme pocket, and the mobility and binding of the substrates
      indicate that they constitute the main contribution to the complex thermodynamic
      reaction volume parameters. This interpretation allows us to conclude that
      cytochrome CYP101, CYP2B4 and CYP102 possess a similar mechanism of substrate
      binding. Interestingly the barotropic behaviors of monomeric cytochrome P450s are
      quite different from those of oligomeric and hetorooligomeric cytochrome P450s.
      The interactions of heterooligomeric subunits influence the stability of
      individual cytochrome P450s and the asymmetric organization of subunits which can
      control and modulate the activity and the recognition with NADPH-cytochrome P450
      reductase.

PMID- 11983405
TI  - Cytochrome P-450-CO and substrates: lessons from ligand binding under high
      pressure.
AB  - An overview of the application of high-pressure studies on the carbon monoxide
      complex of cytochrome P-450 is given. Different approaches to characterize ligand
      binding steps, the conformational states and substates and the compressibility of
      the ligand-bound complex are reviewed. A particular focus is the effect of
      substrates on these properties. It is shown that substrate mobility,
      compressibility and water accessibility are interrelated and may have functional
      meaning.

PMID- 11983406
TI  - Cold denaturation of proteins under high pressure.
AB  - The advantageous usage of the high pressure technique in studies of cold
      denaturation of proteins is reviewed, with a brief explanation of the theoretical
      background of this universal phenomenon. Various experimental results are
      presented and discussed, explaining the plausible image of the cold denatured
      state of proteins. In order to understand more clearly this phenomenon and
      protein structure transition in general, several studies on model polymer systems
      are also reviewed.

PMID- 11983407
TI  - Protein crystallization under high pressure.
AB  - Pressure is expected to be an important parameter to control protein
      crystallization, since hydrostatic pressure affects the whole system uniformly
      and can be changed very rapidly. So far, a lot of studies on protein
      crystallization have been done. Solubility of protein depends on pressure. For
      instance, the solubility of tetragonal lysozyme crystal increased with increasing
      pressure, while that of orthorhombic crystal decreased. The solubility of
      subtilisin increased with increasing pressure. Crystal growth rates of protein
      also depend on pressure. The growth rate of glucose isomerase was significantly
      enhanced with increasing pressure. The growth rate of tetragonal lysozyme crystal
      and subtilisin decreased with increasing pressure. To study the effects of
      pressure on the crystallization more precisely and systematically, hen egg white
      lysozyme is the most suitable protein at this stage, since a lot of data can be
      used. We focused on growth kinetics under high pressure, since extensive studies
      on growth kinetics have already been done at atmospheric pressure, and almost all
      of them have explained the growth mechanisms well. The growth rates of tetragonal
      lysozyme decreased with pressure under the same supersaturation. This means that
      the surface growth kinetics significantly depends on pressure. By analyzing the
      dependence of supersaturation on growth rate, it was found that the increase in
      average ledge surface energy of the two-dimensional nuclei with pressure
      explained the decrease in growth rate. At this stage, it is not clear whether the
      increase in surface energy with increasing pressure is the main reason or not.
      Fundamental studies on protein crystallization under high pressure will be useful
      for high pressure crystallography and high pressure protein science.

PMID- 11983408
TI  - The use of high pressure for separation and production of bioactive molecules.
AB  - Due to its action on the forces governing inter- and intramolecular interactions,
      the application of high pressure to biopurification or bio-elaboration of a
      product are of interest. The two closely thermodynamically related parameters,
      pressure and temperature, render processes based on their action clean, as no
      chemical reagents have to be added (and thus further removed) when they are
      applied. The use of high pressure in the development of desorption methods for
      the purification of bioactive molecules, particularly in the immunoaffinity
      field, is reviewed and discussed. Also mentioned is the application of the
      pressure parameter during the synthesis of a bioreagent. Finally, integrated
      processes relative to the synthesis and purification of these compounds are
      proposed.

PMID- 11983409
TI  - Pressure effects on in vivo microbial processes.
AB  - Pressures between 10 and 100 MPa can exert powerful effects on the growth and
      viability of organisms. Here I describe the effects of elevated pressure in this
      range on mesophilic (atmospheric pressure adapted) and piezophilic (high-pressure
      adapted) microorganisms. Examination of pressure effects on mesophiles makes use
      of this unique physical parameter to aid in the characterization of fundamental
      cellular processes, while in the case of piezophiles it provides information on
      the essence of the adaptation of life to high-pressure environments, which
      comprise the bulk of our biosphere. Research is presented on the isolation of
      pressure-resistant mutants, high-pressure regulation of gene expression, the role
      of membrane lipids and proteins in determining growth ability at high pressure,
      pressure effects on DNA replication and topology as well as on cell division, and
      the role of extrinsic factors in modulating enzyme activity at high pressure.

PMID- 11983410
TI  - Compressibility gives new insight into protein dynamics and enzyme function.
AB  - The adiabatic compressibility of enzyme is largely influenced by binding of
      coenzyme and substrate, due to the changes in atomic packing. Amino acid
      substitution also induces large changes in compressibility parallel to enzyme
      activity. These results demonstrate that a small alteration of local structure by
      ligand binding and mutation is dramatically magnified in the flexibility of
      protein molecule to affect the function. Compressibility gives new insight into
      protein dynamics and enzyme function from the aspect of atomic packing or cavity
      which cannot be obtained by other techniques.

PMID- 11983411
TI  - Experiments on ion channels at high pressure.
AB  - Ion channels are distinctive membrane proteins which provide a gated pathway for
      diffusing ions. High pressure (<100 MPa) affects the kinetics of gating but not
      the conductance of the channel. Dynamic structural studies of channels at high
      pressure are, thus far, conspicuously absent but functional properties are
      studied at the single channel level with the patch clamp technique.

PMID- 11983412
TI  - Cell biology and high pressure: applications and risks.

PMID- 11983413
TI  - Exploring hyperthermophilic proteins under pressure: theoretical aspects and
      experimental findings.
AB  - Proteins from hyperthermophilic microorganisms are generally capable of
      withstanding temperatures close to, or even higher than the boiling point. As a
      rule, these proteins are strongly piezostable as well, although exceptions have
      been also reported. This observation has a theoretical relevance, as the
      understanding of the effects of pressure and temperature on protein stability is
      equally important to develop a comprehensive model for their thermodynamic
      stability. Nevertheless, the structural features justifying the correlation
      between heat resistance and pressure resistance are poorly understood. Actually,
      most reports do not exceed the phenomenological level. Only in the case of the
      small protein Sso7d from Sulfolobus solfataricus, characterisation of wild-type
      and some mutants showed that both properties are largely accounted for by a
      network of aromatic residues found in the hydrophobic core of the molecule.
      Current knowledge, however, does not allow to establish to what extent this
      finding may be generalised. In a biotechnological perspective, hyperthermophilic
      enzymes seem to be more suitable for bioprocesses at high pressure with respect
      to their mesophilic counterparts. Indeed, thanks to their higher resistance
      towards pressure and temperature, they may be exploited in a much broader range
      of working conditions for tuning activity and specificity. Furthermore, they are
      often activated by increasing pressure, although it cannot be established, to
      date, to what extent this is a common feature.

PMID- 11983414
TI  - High pressure in bioscience and biotechnology: pure science encompassed in
      pursuit of value.
AB  - A fundamental factors, pressure (P), is indispensable to develop and support
      applications in the field of bioscience and biotechnology. This short sentence
      describes an example how high pressure bioscience and biotechnology, which
      started from applied science, stimulates challenges of basic science and pure
      science in the biology-related fields including not only food science, medicine,
      and pharmacology but also biochemistry, molecular biology, cell biology, physical
      chemistry, and engineering.

PMID- 11983415
TI  - Human phosphatidylcholine transfer protein: purification, crystallization and
      preliminary X-ray diffraction data.
AB  - We have expressed, purified and crystallized recombinant human
      phosphatidylcholine transfer protein (PC-TP) and selenomethionyl PC-TP bound to
      dilinoleoyl phosphatidylcholine. The biochemical properties of native and
      selenomethionyl PC-TP were indistinguishable, and the two proteins crystallized
      under similar conditions. Both native and selenomethionyl PC-TP crystallized in
      two distinct space groups and diffracted X-rays to 2.4 A resolution.

PMID- 11983416
TI  - Identifying sites of attachment of UV filters to proteins in older human lenses.
AB  - Recent results indicate that covalent modification of proteins by tryptophan
      derived UV filters may explain the age-dependent coloration of human lenses, and
      play a role in age-related cataract. The sites of attachment of the UV filters to
      the lens crystallins, however, have not been determined. This study utilized a
      database of predicted masses of UV filter-modified tryptic peptides to target
      sites of UV filter attachment. Proteins were isolated from old normal lenses and
      digested with trypsin at pH 6, in order to preserve the integrity of the sites of
      modification. Peptides were separated by high-performance liquid chromatography
      and characterized by mass spectrometry. Major colored and fluorescent peaks in
      the digest were found to correspond to cysteine-containing peptides in which the
      sulfur atom of the sidechain was linked to the major UV filter compound, 3
      hydroxykynurenine glucoside. Three of the peptides originated from gammaS
      crystallin and one from betaB1-crystallin. These results show that a predicted
      mass database can be used to facilitate the identification of sites of UV filter
      modification in human lens crystallins. Furthermore, this work represents the
      first evidence that UV filters bind to specific residues on lens proteins in
      vivo, and suggests that sulfhydryl groups may be important sites for the
      attachment of UV filters.

PMID- 11983417
TI  - In vitro stepwise autoprocessing of the proform of pro-aminopeptidase processing
      protease from Aeromonas caviae T-64.
AB  - PA protease (pro-aminopeptidase processing protease) is an extracellular zinc
      metalloprotease produced by the Gram-negative bacterium Aeromonas caviae T-64.
      The 590-amino-acid precursor of PA protease is composed of a putative 19-amino
      acid signal sequence, a 165-amino-acid N-terminal propeptide, a 33 kDa mature
      protease domain and an 11 kDa C-terminal propeptide. The proform of PA protease,
      which was produced as inclusion bodies in Escherichia coli, was subjected to in
      vitro refolding. It was revealed that the processing of the proform involved a
      stepwise autoprocessing mechanism. Firstly, the N-terminal propeptide was
      autocatalytically removed on completion of refolding and secondly, the C-terminal
      propeptide was autoprocessed after the degradation of the N-terminal propeptide.
      Both the N- and C-terminal propeptides existed as intact peptides after their
      successive removal, and they were subsequently degraded gradually. The
      degradation of the N-terminal propeptide appears to be the rate-limiting step in
      the maturation of the proform of PA protease.

PMID- 11983418
TI  - The receptor docking segment and S-adenosyl-L-homocysteine bind independently to
      the methyltransferase of bacterial chemotaxis.
AB  - To mediate adaptation to stimuli, the methyltransferase (CheR) catalyzes methyl
      group transfer from S-adenosyl-L-methionine (SAM) to glutamyl residues in the
      transmembrane receptors of the bacterial chemosensory signaling pathway. The
      interaction between receptors and CheR occurs at two sites: a methylation site
      active site interaction, and a 'docking' site interaction that is separated both
      from the methylation sites and the CheR active site. It is not certain if the
      docking site interaction functions merely to localize the transferase in close
      proximity to the methylation sites, or if it also increases CheR catalytic
      activity. Isothermal titration calorimetry experiments are conducted to test for
      allosteric interactions between the docking and active sites on CheR, which are
      expected to be present if docking activates CheR. The binding parameters (DeltaG,
      DeltaH, DeltaS) of a substrate analog of SAM, S-adenosyl-L-homocysteine (SAH),
      are measured both in the absence and presence of saturating concentrations of a
      pentapeptide (NWETF) that defines the docking receptor docking segment. SAH
      binding is unaffected by the presence of saturating NWETF, providing evidence
      that an allosteric activation of CheR does not take place upon docking, and thus
      supports the idea that the CheR-NWETF interaction merely functions to localize
      CheR near the sites of methylation.

PMID- 11983419
TI  - Upward shift of the pH optimum of Acremonium ascorbate oxidase.
AB  - A gene encoding a thermostable Acremonium ascorbate oxidase (ASOM) was randomly
      mutated to generate mutant enzymes with altered pH optima. One of the mutants,
      which exhibited a significantly higher activity in the pH range 4.5-7 compared to
      ASOM, had a Gln183Arg substitution in the region corresponding to SBR1, one of
      the substrate binding regions of the zucchini enzyme. The other mutant with
      almost the same pH profile as Gln183Arg had a Thr527Ala substitution near the
      type 3 copper center and became more sensitive to azide than ASOM. Site-directed
      mutagenesis in the substrate binding regions with reference to the amino acid
      sequences of plant enzymes led to isolation of mutants shifted upward in the pH
      optimum; Val193Pro and Val193Pro/Pro190Ile increased the pH optimum by 1 and 0.5
      units, respectively, while retaining the near-wild-type thermostability and azide
      sensitivity. The homology model of ASOM constructed from the zucchini enzyme
      coordinates suggested that replacement of Val193 by Pro could disturb the ion
      pair networks among Arg309, Glu192, Arg194 and Glu311. This perturbation could
      affect either the molecular recognition between the substrate and ASOM or the
      electron transfer from the substrate to the type 1 copper center, leading to the
      alkaline shift of the catalytic activity of the mutant enzyme. The other
      mutations, Val193Pro/Pro190Ile, could also induce similar structural
      perturbations involving the ion pair networks.

PMID- 11983420
TI  - Unfolding of pyridoxal 5'-phosphate-dependent O-acetylserine sulfhydrylase probed
      by time-resolved tryptophan fluorescence.
AB  - Proteins utilizing pyridoxal 5'-phosphate as a coenzyme constitute a large
      superfamily and are currently classified into three functional groups and five
      structural fold types. Despite the variability of sequences and catalyzed
      reactions, they share relevant structural, dynamic and functional properties.
      Therefore, they constitute an optimal system to investigate the relative
      influence of primary sequence and coenzyme interactions on folding pathways,
      structural stability and enzymatic function. O-Acetylserine sulfhydrylase is a
      dimeric pyridoxal 5'-phosphate dependent enzyme that catalyzes the synthesis of L
      cysteine from O-acetylserine and sulfide. The time-resolved fluorescence study of
      O-acetylserine sulfhydrylase unfolding, here reported, indicates that the
      coenzyme stabilizes the protein structure. The dependence on denaturant
      concentration of tryptophan lifetimes in the holo- and apo-enzyme demonstrates
      that the interactions with the coenzyme stabilize the C-terminal domain to a
      higher extent with respect to the N-terminal domain. This result is discussed in
      terms of a linkage between the differential stabilization brought about by the
      coenzyme and the different degrees of conformational flexibility required by the
      specialized functional role of distinct protein regions.

PMID- 11983421
TI  - Design of new and sensitive fluorogenic substrates for human kallikrein hK3
      (prostate-specific antigen) derived from semenogelin sequences.
AB  - Human kallikrein hK3 (prostate-specific antigen) is a chymotrypsin-like serine
      protease which is widely used in the diagnosis of prostate cancer. Assays of the
      enzymatic activity of hK3 in extracellular fluids have been limited by a lack of
      sensitive synthetic substrates. This report describes the design of a series of
      internally quenched fluorescent peptides containing an amino acid sequence based
      on preferential hK3 cleavage sites in semenogelins. Those were identified by 2-D
      gel electrophoresis analysis and N-terminal sequencing of semenogelin fragments
      generated by ex vivo proteolysis in freshly ejaculated semen. These peptides were
      cleaved by hK3 at the C-terminal of certain tyrosyl or glutaminyl residues with
      k(cat)/K(m) values of 15000-60000 M(-1) s(-1). The substrate Abz-SSIYSQTEEQ-EDDnp
      was cleaved at the Tyr-Ser bond with a specificity constant k(cat)/K(m) of 60000
      M(-1) s(-1), making it the best substrate for hK3 described to date.

PMID- 11983422
TI  - Reaction of hydrogen peroxide and peroxidase activity in carboxymethylated
      cytochrome c: spectroscopic and kinetic studies.
AB  - The peroxidase activity of carboxymethylated cytochrome c (Cmcytc) has been
      investigated by spectroscopic and kinetic techniques to examine the effect of
      carboxymethylation on the peroxidase activity of native cytochrome c (cytc). The
      optical spectrum suggests that the reaction of Cmcytc with H(2)O(2) proceeds
      through only one intermediate, compound I. The apparent rate constant (k(app))
      for the reaction was found to be 17, 72 and 210 M(-1) s(-1) at pH 7.0, 5.0 and
      3.5 respectively. These values are about 60 times larger than those reported for
      native cytc (0.236 M(-1) s(-1) at pH 7.0), and about five orders of magnitude
      lower than those for classical peroxidases. Cmcytc was found to catalyse
      oxidation of organic and inorganic substrates. The second order rate constant for
      the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) by
      Cmcytc (205 [H(2)O(2)] s(-1)) is found to be larger than the corresponding value
      for native cytc (50 [H(2)O(2)] s(-1)) at pH 6.0. The carboxymethylation of cytc
      ruptures the Fe-S (Met 80) bond and increases the rate of its reaction with
      H(2)O(2), and its catalytic activity. The specific activity of Cmcytc was
      measured spectrophotometrically by the reported method using ABTS as substrate,
      and was found to be 288, 473 and 872 microM min(-1) mg(-1) at pH 7.0, 5.0 and 3.5
      respectively. Resonance Raman studies indicated the presence of a bis-histidine
      coordinated form of Cmcytc at neutral pH, and the existence of a population
      distribution of different ligation states such as bis-histidine (HH), histidine
      water (HW) and five coordinate (5C) forms at lower pH. The relative population of
      different species in Cmcytc was found to be HH (approximately 100%, approximately
      50%, approximately 44%), HW (approximately 0%, approximately 44%, 41%) and 5C
      (approximately 0%, approximately 6%, 15%) at pH 7.0, 4.7 and 3.1 respectively. We
      have attempted to correlate the pH dependence of the reaction of Cmcytc with
      hydrogen peroxide and its peroxidase activity with the haem stereochemical
      structures observed for Cmcytc. Steady-state and time-resolved tryptophan
      fluorescence studies on Cmcytc were done to probe the conformational changes
      around the haem pocket of Cmcytc.

PMID- 11983423
TI  - Aspartic proteinase inhibitors from tomato and potato are more potent against
      yeast proteinase A than cathepsin D.
AB  - The interaction of a variety of aspartic proteinases with a recombinant tomato
      protein produced in Pichia pastoris was investigated. Only human cathepsin D and,
      even more potently, proteinase A from Saccharomyces cerevisiae were inhibited.
      The tomato polypeptide has >80% sequence identity to a previously reported potato
      inhibitor of cathepsin D. Re-evaluation of the potato inhibitor revealed that it
      too was more potent (>20-fold) towards yeast proteinase A than cathepsin D and so
      might be renamed the potato inhibitor of proteinase A. The potency towards yeast
      proteinase A may reflect a similarity between this fungal enzyme and aspartic
      proteinases produced by fungal pathogens which attack tomato and/or potatoes.

PMID- 11983424
TI  - Hydrolysis of pectins with different degrees and patterns of methylation by the
      endopolygalacturonase of Fusarium moniliforme.
AB  - The mode of action of the endopolygalacturonase from Fusarium moniliforme was
      studied towards a series of pectins with different amounts and distribution
      patterns of methyl-ester groups. The enzyme hydrolysed the linkages between two
      galacturonic acid residues according to a multi-chain attack mechanism, at least
      at the early stage of the reaction. The final percentage of hydrolysis decreased
      with increasing the degree of methylation. The distribution pattern of the methyl
      groups affected the rate of hydrolysis as well as the final percentage of
      hydrolysis, a blockwise distribution being more favourable than a random one. The
      final products, as analysed by mass spectrometry, included methyl-esterified
      oligogalacturonates. The detailed analysis of the structure of the oligomers
      showed that the enzyme was able to accommodate methylated galacturonic acid in
      its active site, but that methyl-esterification negatively affected the affinity
      of the enzyme.

PMID- 11983425
TI  - Study of substrate-enzyme interaction between immobilized pyridoxamine and
      recombinant porcine pyridoxal kinase using surface plasmon resonance biosensor.
AB  - Pyridoxal kinase (PK) is an important enzyme involved in bioactivation of vitamin
      B(6). Binding of PK with its substrate is the prerequisite step for the
      subsequent catalytic phosphorylation of the substrate. In the present study, a
      surface plasmon resonance biosensor (BIAcore) was employed to characterize the
      binding interaction between wild-type porcine PK and an immobilized substrate,
      pyridoxamine. Pyridoxamine was modified with 11-mercaptoundecanic acid and
      immobilized on a sensor chip through the formation of a self-assembled monolayer.
      The binding of PK to the immobilized pyridoxamine was followed in real time and
      the kinetic parameters were derived from non-linear analysis of the sensorgram.
      The effects of buffer pH, monovalent cations (Na(+), K(+)) and divalent cations
      (Mn(2+), Zn(2+), Mg(2+)) on the binding kinetics were determined. Optimal pH for
      PK-pyridoxamine interaction in the absence of divalent ions is at around 7.4.
      While K(+) increased and Na(+) decreased the binding affinity (K(A)) of PK to
      immobilized pyridoxamine, all divalent cations increased the K(A) of PK for
      pyridoxamine. Solution phase affinity measurement based on a competitive binding
      assay was used to determine the affinities of PK for different vitamin B(6)
      analogues. The order of affinity of PK for different analogues is: pyridoxal
      oxime>pyridoxine>pyridoxamine>pyridoxal>pyridoxal phosphate. This is the first
      study to demonstrate that buffer conditions such as pH and concentration of
      monovalent and/or divalent ions can directly alter the binding of PK for its
      substrates. The quantitative kinetic and thermodynamic parameters obtained by SPR
      measurement provide the insight information into the catalytic activity of this
      enzyme.

PMID- 11983426
TI  - Legumain from bovine kidney: its purification, molecular cloning,
      immunohistochemical localization and degradation of annexin II and vitamin D
      binding protein.
AB  - Legumain (asparaginyl endopeptidase) was purified to homogeneity from bovine
      kidneys. The molecular mass of the purified enzyme was calculated to be 34000 by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of beta
      mercaptoethanol. The enzyme rapidly hydrolyzed the substrate Z-Ala-Ala-Asn-MCA
      and was strongly inhibited by N-ethylmaleimide, p-chloromercuribenzene-sulfonic
      acid, Hg(2+) and Cu(2+). The amino acid sequence of the first 26 residues of the
      enzyme was Gly-Gly-Lys-His-Trp-Val-Val-Ile-Val-Ala-Gly-Ser-Asn-Gly-Gln-Tyr-Asn
      Tyr-Arg-His-Gln-Ala-Phe-Ala-Asp-His-. This sequence is highly homologous to the
      sequences in the N-terminal of pig kidney legumain. We screened a bovine kidney
      cortex cDNA library using a DNA probe that originated from rat legumain, and we
      determined the bovine kidney cDNA structure and deduced the amino acid sequence.
      The cDNA is composed 1934 bp and encodes 433 amino acids in the coding region.
      The enzyme was strongly stained in the proximal tubules of the rat kidney in an
      immunohistochemical study. Vitamin D-binding protein which is known to be a
      ligand to megalin existing in the proximal tubules, was cleaved in a limited
      proteolytic manner by bovine kidney legumain. These results suggested that
      legumain contributes to the processing of macromolecules absorbed by proximal
      tubule cells. The enzyme also cleaved an N-terminal synthetic peptide of bovine
      annexin II (Gly(24)-Ser-Val-Lys-Ala-Tyr-Thr(30)-Asn-Phe-Asp-Ala-Glu(35)-Arg
      Asp(37)) at a position between Asn(31) and Phe(32). The amino-terminal domain of
      annexin II has p11 subunit binding sites and phosphorylation sites for both
      pp60(src) and protein kinase C. This suggests that legumain plays an important
      role in inactivation and degradation of annexin II, which is abundant in the
      receptor-recycling compartments of endosomes/lysosomes.

PMID- 11983427
TI  - Phosphorylation of the minimal inhibitory region at the C-terminus of caldesmon
      alters its structural and actin binding properties.
AB  - Caldesmon is an inhibitory protein believed to be involved in the regulation of
      thin filament activity in smooth muscles and is a major cytoplasmic substrate for
      MAP kinase. NMR spectroscopy shows that the actin binding properties of the
      minimal inhibitory region of caldesmon, residues 750-779, alter upon MAP kinase
      phosphorylation of Ser-759, a residue not involved in actin binding. This
      phosphorylation leads to markedly diminished actin affinity as a result of the
      loss of interaction at one of the two sites that bind to F-actin. The structural
      basis for the altered interaction is identified from the observation that
      phosphorylation destabilises a turn segment linking the two actin binding sites
      and thereby results in the randomisation of their relative disposition. This
      modulatory influence of Ser-759 phosphorylation is not merely a function of the
      bulkiness of the covalent modification since the stability of the turn region is
      observed to be sensitive to the ionisation state of the phosphate group. The data
      are discussed in the context of the inhibitory association of the C-terminal
      domain of caldesmon with F-actin.

PMID- 11983428
TI  - Stromal interaction molecule 1 (STIM1), a transmembrane protein with growth
      suppressor activity, contains an extracellular SAM domain modified by N-linked
      glycosylation.
AB  - Stromal interaction molecule 1 (STIM1) is a cell surface transmembrane
      glycoprotein implicated in tumour growth control and stromal-haematopoietic cell
      interactions. A single sterile alpha motif (SAM) protein-protein interaction
      domain is modelled within its extracellular region, a subcellular localisation
      not previously described for other SAM domain-containing proteins. We have
      defined the transmembrane topology of STIM1 by determining the sites of N-linked
      glycosylation. We have confirmed that STIM1 is modified by N-linked glycosylation
      at two sites within the SAM domain itself, deduced as asparagine residues N131
      and N171, demonstrating that STIM1 is translocated across the membrane of the
      endoplasmic reticulum such that the SAM domain resides within the endoplasmic
      reticulum (ER) lumen. Both N-linked oligosaccharides remain endoglycosidase H
      sensitive, indicating absence of full processing within the ER and Golgi. This
      immature modification is nevertheless sufficient and critical for cell surface
      expression of STIM1. We show that STIM1-STIM1 homotypic interactions are mediated
      via the cytoplasmic rather than the extracellular region of STIM1, excluding an
      essential role for the SAM domain in these protein interactions. These studies
      provide the first evidence for an extracellular localisation of a SAM domain
      within any protein, and the first example of a SAM domain modified by N-linked
      glycosylation.

PMID- 11983429
TI  - Unraveling multistate unfolding of rabbit muscle creatine kinase.
AB  - GdmCl-induced unfolding of rabbit muscle creatine kinase, CK, has been studied by
      a variety of physico-chemical methods including near and far UV CD, SEC,
      intrinsic fluorescence (intensity, anisotropy and lifetime) as well as intensity
      and lifetime of bound ANS fluorescence. The formation of several stable unfolding
      intermediates, some of which were not observed previously, has been established.
      This was further confirmed by representation of fluorescence data in terms of
      "phase diagram", i.e. I(lambda1) versus I(lambda2) dependence, where I(lambda1)
      and I(lambda2) are fluorescence intensity values measured on wavelengths
      lambda(1) and lambda(2) under the different experimental conditions for a protein
      undergoing structural transformations. The unfolding behavior of CK was shown to
      be strongly affected by association of partially folded intermediates. A model of
      CK unfolding, which takes into account both structural perturbations and
      association of partially folded intermediates has been elaborated.

PMID- 11983430
TI  - Kinetic analysis of mouse retinal dehydrogenase type-2 (RALDH2) for retinal
      substrates.
AB  - Retinal dehydrogenase (RALDH) isozymes catalyze the terminal oxidation of retinol
      into retinoic acid (RA) that is essential for embryogenesis and tissue
      differentiation. To understand the role of mouse type 2 RALDH in synthesizing the
      ligands (all-trans and 9-cis RA) needed to bind and activate nuclear RA
      receptors, we determined the detailed kinetic properties of RALDH2 for various
      retinal substrates. Purified recombinant RALDH2 showed a pH optimum of 9.0 for
      all-trans retinal oxidation. The activity of the enzyme was lower at 37 degrees C
      compared to 25 degrees C. The efficiency of conversion of all-trans retinal to RA
      was 2- and 5-fold higher than 13-cis and 9-cis retinal, respectively. The K(m)
      for all-trans and 13-cis retinal were similar (0.66 and 0.62 microM,
      respectively). However, the K(m) of RALDH2 for 9-cis retinal substrate (2.25
      microM) was 3-fold higher compared to all-trans and 13-cis retinal substrates.
      Among several reagents tested for their ability to either inhibit or activate
      RALDH2, citral and para-hydroxymercuribenzoic acid (p-HMB) inhibited and MgCl(2)
      activated the reaction. Comparison of the kinetic properties of RALDH2 for
      retinal substrates and its activity towards various reagents with those of
      previously reported rat kidney RALDH1 and human liver aldehyde dehydrogenase-1
      showed distinct differences. Since RALDH2 has low K(m) and high catalytic
      efficiency for all-trans retinal, it may likely be involved in the production of
      all-trans RA in vivo.

PMID- 11983431
TI  - Unfolding the unique c-type heme protein, Chlamydomonas reinhardtii cytochrome f.
AB  - We have studied the unfolding reaction of cytochrome f from the green alga
      Chlamydomonas reinhardtii. Cytochrome f is different from all other c-type heme
      proteins in that it is a large, two-domain protein with predominantly beta-sheet
      structure. Moreover, the sixth axial ligand to the heme-iron is unique in
      cytochrome f: it is provided by the N-terminal alpha-amino group. Unfolding of
      oxidized and reduced cytochrome f by guanidine hydrochloride (GuHCl) was
      monitored by far-UV circular dichroism (CD), Soret absorption, and tyrosine
      emission: the same unfolding curves were obtained regardless of method. Neither
      oxidized nor reduced unfolded cytochrome f can be refolded at neutral pH. At pH
      3.5 refolding takes place (upon dilution to lower denaturant concentrations or by
      electron injection to the unfolded, oxidized form), although the reaction is
      extremely slow. Reduced cytochrome f appears much more resistant towards
      denaturant perturbation than the oxidized form (in pH range 7-3.5). The heme in
      unfolded cytochrome f remains low-spin to pH 4 but turns high-spin at pH 3.5
      (presumably due to protonation of the N-terminal amino group). Our results
      suggest that the unfolding process for cytochrome f is complex, involving
      kinetically trapped intermediates not resolvable by spectroscopy.

PMID- 11983432
TI  - Phase correction in sensorimotor synchronization: nonlinearities in voluntary and
      involuntary responses to perturbations.
AB  - When finger taps are synchronized with an auditory sequence, both a global phase
      shift (PS) and a local event onset shift (EOS) in the sequence elicit a phase
      correction response (PCR) on the next tap. The PCR to an expected PS is intended
      and large, whereas that to an expected EOS is unintended and smaller. PCR
      magnitude increases linearly with perturbation magnitude up to about +/-15% of
      the sequence period (500 milliseconds). With larger perturbations, voluntary PCRs
      increase more slowly whereas involuntary PCRs reach an asymptote. These results,
      obtained previously in a blocked design [J. Exp. Psychol. Human Percept. Perform.
      (in press)], were replicated in a randomized design and in two additional task
      contexts that varied participants' intentions while neutralizing their
      expectations. Neither design nor expectations seemed to play a role. However,
      considerable individual differences were noted. The results confirm that phase
      correction is partially automatic and partially subject to voluntary control, and
      they provide empirical estimates of error correction functions that may be useful
      in formal modeling of sensorimotor synchronization behavior.

PMID- 11983433
TI  - Local stability in coordinated rhythmic movements: fluctuations and relaxation
      times.
AB  - An experiment was conducted to examine the stability of the anti-phase and in
      phase modes of coordination by means of both fluctuations and relaxation times.
      Participants (n=6) performed a rhythmic bimanual forearm coordination task that
      required them to oscillate their forearms in-phase and anti-phase while grasping
      two manipulanda at fixed frequencies ranging from 0.6 to 1.8 Hz. Relaxation times
      were measured as the time taken to return to a stable mode following the
      application of a transient mechanical torque. It was found that relaxation times
      were not different statistically across participants, frequencies, and
      coordinative modes. However, fluctuations, as indicated by the mean S.D. of
      relative phase across individual frequency plateaus, were significantly greater
      in the anti-phase than in the in-phase mode of coordination, p<0.05. Whilst
      providing new empirical support for the notion that relaxation times should be of
      the same order of magnitude at frequencies outside transition regions, the
      findings suggest that the level of stochastic noise in the anti-phase mode is
      greater than that of the in-phase mode. Implications are made for the future
      assessment of local pattern stability.

PMID- 11983434
TI  - Postural orientation: age-related changes in variability and time-to-boundary.
AB  - The relation between age-specific postural instability and the detection of
      stability boundaries was examined. Balance control was investigated under
      different visual conditions (eyes open/closed) and postural orientations
      (forward/backward lean) while standing on a force platform. Dependent variables
      included center of pressure variability and the time-to-contact of the center of
      pressure with the stability boundaries around the feet (i.e., time-to-boundary).
      While leaning maximally, older individuals (ages 55-69) showed increased center
      of pressure variability compared to no lean, while younger subjects (ages 24-38)
      showed a decrease. These significant differences were found only in anterior
      posterior direction. No significant age-specific differences were found between
      eyes open and eyes closed conditions. Time-to-boundary analysis revealed reduced
      spatio-temporal stability margins in older individuals in both anterior-posterior
      and medio-lateral directions. Time-to-boundary variability, however, was not
      significantly different between the groups in both medio-lateral and anterior
      posterior direction. These results show the importance of boundary relevant
      center of pressure measures in the study of postural control, especially
      concerning the lateral instability often observed in older adults.

PMID- 11983435
TI  - Relative damping improves linear mass-spring models of goal-directed movements.
AB  - A limitation of a simple linear mass-spring model in describing goal directed
      movements is that it generates rather slow movements when the parameters are kept
      within a realistic range. Does this imply that the control of fast movements
      cannot be approximated by a linear system? In servo-control theory, it has been
      proposed that an optimal controller should control movement velocity in addition
      to position. Instead of explicitly controlling the velocity, we propose to modify
      a simple linear mass-spring model. We replaced the damping relative to the
      environment (absolute damping) with damping with respect to the velocity of the
      equilibrium point (relative damping). This gives the limb a tendency to move as
      fast as the equilibrium point. We show that such extremely simple models can
      generate rapid single-joint movements. The resulting maximal movement velocities
      were almost equal to those of the equilibrium point, which provides a simple
      mechanism for the control of movement speed. We further show that peculiar
      experimental results, such as an 'N-shaped' equilibrium trajectory and the
      difficulties to measure damping in dynamic conditions, may result from fitting a
      model with absolute damping where one with relative damping would be more
      appropriate. Finally, we show that the model with relative damping can be used to
      model subtle differences between multi-joint interceptions. The model with
      relative damping fits the data much better than a version of the model with
      absolute damping.

PMID- 11983436
TI  - Effects of proprioceptive neuromuscular facilitation on the initiation of
      voluntary movement and motor evoked potentials in upper limb muscles.
AB  - To better understand the mechanisms behind proprioceptive neuromuscular
      facilitation (PNF), an important method in motor rehabilitation, we investigated
      the effects of assuming a PNF posture relative to a neutral posture on the
      initiation of voluntary movement (Experiment 1) and the excitability of the motor
      cortex (Experiment 2) using a wrist extension task. The initiation of voluntary
      wrist movement was operationalized in terms of the electromyographic reaction
      time (EMG-RT), and the excitability of the motor cortex in terms of motor evoked
      potentials (MEPs). Compared to the neutral position, we found that (1) the
      facilitation position changed the muscle discharge order enhancing the movement
      efficiency of the joint, (2) the facilitation position led to a reduction in EMG
      RT, the magnitude of which depended on the proximity of the muscle to the
      movement joint, and (3) MEP amplitude increased and MEP latency decreased in the
      facilitation position as a function of the proximity of the muscle to the joint.
      These findings corroborate the presumed effects of PNF and provide insights into
      the neurophysiological mechanisms underlying the PNF method.

PMID- 11983439
TI  - Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA
      clone derived from a blood-borne non-A, non-B viral hepatitis genome [Science
      1989;244:359-362].

PMID- 11983440
TI  - Natural history and outcome in 32 Swedish patients with small duct primary
      sclerosing cholangitis (PSC).
AB  - BACKGROUND/AIMS: This study aims at describing the natural history and outcome of
      small duct primary sclerosing cholangitis (PSC). METHODS: Thirty-two patients
      with small duct PSC were studied. The average time taken for diagnosis was 69 (1
      168) months. The median follow-up time was 63 (1-194) months. RESULTS: All
      patients including one who underwent liver transplantation because of end-stage
      liver disease and hepatocellular carcinoma were alive at follow-up. None
      developed cholangiocarcinoma. In 27 patients repeated cholangiographic
      examinations were done after a median time of 72 (12-192) months from first ERCP.
      Four developed features of large duct PSC. CONCLUSIONS: Small duct PSC rarely
      progresses to large bile duct PSC and it seems to have a benign course in most
      patients and no development of cholangiocarcinoma was found.

PMID- 11983441
TI  - Regulation of cultured rat hepatocyte proliferation by stellate cells.
AB  - BACKGROUND/AIMS: This study using primary culture models was aimed to reveal the
      stellate cell-derived factors that regulate hepatocyte proliferation. METHODS:
      Rat hepatocytes and stellate cells were cultured in serum-free Williams-E medium.
      We prepared hepatocyte mono-culture and two different co-cultures of hepatocytes
      and stellate cells; (1) co-culture on the same surface (Co-mix.) and (2) co
      culture without contact between hepatocytes and stellate cells using a culture
      insert (Co-sep.). The change in the number and the DNA synthesis of hepatocytes
      was evaluated. RESULTS: The number of hepatocytes decreased to 76% of the
      original number after 48 h of starting mono-culture, while it remained at 106% in
      mixed co-culture (Co-mix.) and increased to 135% in separated co-culture (Co
      sep.). The hepatocyte DNA synthesis was enhanced by carbenoxolone in Co-mix. and
      reduced by NK1 in each co-culture. PD153035 had no effect. Heparitinase-I (20
      mU/ml) and sodium chrolate (25 mM) reduced the hepatocyte DNA synthesis in Co
      sep. to 71.8 and 61.6%, respectively. Activation of mitogen-activated protein
      kinase was induced in hepatocytes stimulated by conditioned mediums. CONCLUSIONS:
      Hepatocyte proliferation was stimulated in the presence of stellate cells through
      hepatocyte growth factor, extracellular heparan sulfate (HS), and HS
      proteoglycan, and might be negatively regulated by gap junction-dependent
      mechanism.

PMID- 11983442
TI  - Effect of 1-week losartan administration on bile duct-ligated cirrhotic rats with
      portal hypertension.
AB  - BACKGROUND/AIMS: Nitric oxide and angiotensin play important roles in the
      pathogenesis of the hemodynamic derangement in cirrhosis and portal hypertension.
      The hemodynamic effects of losartan, an angiotensin II type 1 receptor
      antagonist, in cirrhotic patients with portal hypertension are conflicting. This
      study was undertaken to explore the possible mechanism of action of losartan on
      portal hypertension in cirrhotic rats produced by bile duct ligation (CBL).
      METHODS: Three weeks after surgery, CBL and sham-operated rats randomly received
      vehicle or losartan (3 mg/kg per 12 h by gavage) for 1 week. Hemodynamic values,
      hormone levels, and aortic eNOS protein expression were measured after drug
      administration. RESULTS: In CBL rats, 1-week losartan treatment decreased portal
      pressure and ameliorated hyperdynamic circulation associated with a blunted
      vascular response to N(omega)-nitro-L-arginine methyl ester infusion. The
      hematocrit increased and the plasma volume, aldosterone, plasma renin activity,
      norepinephrine, and nitrate and nitrite levels decreased. The eNOS protein
      expression was reduced in CBL rats receiving losartan compared with those
      receiving vehicle. CONCLUSIONS: One-week losartan treatment in CBL rats decreased
      portal pressure and ameliorated hyperdynamic circulation. In addition to the
      suppression of renin-angiotensin axis, the reduced aortic eNOS protein expression
      may play a partial role for the mechanism of action of losartan in CBL rats.

PMID- 11983443
TI  - Expression of reelin in hepatic stellate cells and during hepatic tissue repair:
      a novel marker for the differentiation of HSC from other liver myofibroblasts.
AB  - BACKGROUND/AIMS: Hepatic stellate cells (HSC) and rat liver myofibroblasts (rMF),
      two similar but not identical cell populations, play a major role during hepatic
      tissue repair. METHODS: To identify marker proteins for the different
      fibroblastic cell populations, m-RNA-profiling technology was employed using c
      DNAs prepared from HSC and rMF. RESULTS/CONCLUSIONS: The extracellular matrix
      protein reelin was identified through its presence in HSC and absence in rMF
      derived samples. As confirmed by Northern blot analysis and by
      immunoprecipitation, reelin expression was present in similar amounts in resting
      and activated HSC and was not detectable in rMF. Therefore reelin is the only
      marker presently available to distinguish HSC at any stage of differentiation
      from rMF. Following a single CCl4 mediated liver injury, reelin specific mRNAs
      were induced early, were elevated up to 24 h following CCl4 dosage and were
      diminished afterwards. Hepatocytes and non-parenchymal liver cells located in the
      damaged areas were identified as the main cellular source of enhanced reelin
      expression. Although reelin expression was upregulated during liver injury,
      reelin deficient mice recovered completely suggesting either a more distinct role
      in tissue repair reactions or a case of redundancy through the action of related
      proteins.

PMID- 11983444
TI  - Liver injury due to sequential activation of natural killer cells and natural
      killer T cells by carrageenan.
AB  - BACKGROUND/AIMS: Carrageenan is a high molecular weight polysaccharide and is
      widely used as a food additive for the solidification of plant oils and the
      thickening of many beverages. It is known that acute toxicity of carrageenan is
      possibly induced by the activation of phagocytic cells. We investigated other
      effects of carrageenan on lymphocytes in this study. METHODS: Carrageenan was
      intraperitoneally injected once into mice and phenotypic and functional
      characterizations were conducted in various immune organs. RESULTS: Natural
      killer (NK) cells were prominently activated in the liver, lungs, and spleen. A
      time-kinetic study showed sequential activation of NK and natural killer T (NKT)
      cells in the liver on days 3-10 after the injection. In parallel with the
      activation of NK and NKT cells in number, NK and NKT cytotoxicities were
      augmented. At this time, liver injury was induced, accompanied by massive hepatic
      necrosis and the elevation of transaminases. The in vivo elimination of NK cells
      reduced the liver injury induced by carrageenan. Direct binding of carrageenan
      onto NK cells was also demonstrated. Such a binding then induced a subsequent
      production of IFN gamma. Perforin molecules of NK cells were responsible for this
      liver injury. CONCLUSIONS: These results suggest that not only phagocytic cells
      but also primitive lymphocyte (mainly NK cells) subsets might be important
      targets for the acute toxicity of carrageenan.

PMID- 11983445
TI  - The role of endogenous heme oxygenase in the initiation of liver injury following
      limb ischemia/reperfusion.
AB  - BACKGROUND/AIMS: Heme oxygenase (HO) derived liver protection was tested in mice
      following 1 h bilateral hindlimb ischemia and either 1.5 or 3 h reperfusion.
      METHODS: Groups consisted of limb ischemia/reperfusion (I/R), sham (no I/R),
      I/R+chromium mesoporphyrin (I/R+CrMP;40 micromol/kg, i.p.), or I/R+hemin (10
      mg/kg, i.p.). The vital dye propidium iodide (PI), was used to measure
      hepatocellular death (#/0.1 mm(3)), while the number of sinusoids perfused by red
      blood cells (SP(RBC)) were measured from the periportal (Pp) and pericentral (Pc)
      zones of liver acini using intravital microscopy. Whole organ injury was
      estimated from serum alanine aminotransferase (ALT). RESULTS: SP(RBC) reduced
      within 1.5 h with no further decline following 3 h. CrMP resulted in a dramatic
      loss of SP(RBC) following 3 h only. Hemin restored perfusion in both zones.
      Hepatocellular death and organ injury increased at 1.5 and 3 h. At 1.5 h, CrMP
      further increased cell death in the Pc zone, as well as whole organ injury, while
      hemin restored cell viability. Increased HO mRNA, protein and activity suggested
      induction within 3 h. CONCLUSIONS: HO does not protect perfusion during the early
      stage (1.5 h), but becomes increasingly important in preserving liver perfusion
      and cell viability during the later stage (3 h) of liver injury.

PMID- 11983446
TI  - 4-Nitrobenzylidene malononitrile reduces apoptosis-mediated liver injury in mice.
AB  - BACKGROUND: Apoptosis plays a role in experimental and clinically related liver
      damage. Inhibitors of tyrosine kinases were shown to modulate apoptosis induced
      by different agents in various cell types. AIMS: Investigation of the effect of 4
      nitrobenzylidene malononitrile (belonging to the tyrphostins family which are
      selective inhibitors of protein tyrosine kinases) on apoptosis-mediated acute
      liver injury. METHODS: Two murine experimental models exhibiting apoptosis
      mediated liver injury were used: (1) mice treated with tumor necrosis factor
      alpha and D-galactosamine; and (2) mice treated with anti-Fas antibody. Liver
      injury was assessed by serum levels of transaminases and by microscopic analysis.
      Apoptosis was assessed by labeling of apoptotic cells in the liver by the TUNEL
      assay and by determination of caspase-3 activity. RESULTS: Pretreatment of mice
      with 4-nitrobenzylidene malononitrile reduced tumor necrosis factor-alpha/D
      galactosamine-induced hepatotoxicity. TUNEL positive cells in sections from
      livers treated with vehicle (control), 4-nitrobenzylidene malononitrile, tumor
      necrosis factor-/d-galactosamine and tumor necrosis factor-alpha/D-galactosamine
      and 4-nitrobenzylidene malononitrile, were >0.2, >0.2, 49+/-2.3 and 4+/-0.2 per
      mm(2), respectively. 4-Nitrobenzylidene malononitrile also reduced hepatotoxicity
      induced by anti-Fas antibody. Caspase-3 activation induced by either tumor
      necrosis factor-alpha/D-glactosamine or by anti-Fas treatment, was reduced by
      pretreatment with N-nitrobenzylidene malononitrile. CONCLUSIONS: The findings may
      provide a base for development of a new therapeutic modality to reduce apoptosis
      mediated liver damage.

PMID- 11983447
TI  - Inhibition of urokinase-type plasminogen activator delays expression of c-jun,
      activated transforming growth factor beta 1, and matrix metalloproteinase 2
      during post-hepatectomy liver regeneration in mice.
AB  - BACKGROUND/AIMS: Although urokinase-type plasminogen activator (u-PA) is
      suggested to initiate various factors in liver regeneration after hepatectomy, no
      corroborative evidence has been reported. In the present study, we investigated
      the effect of u-PA on liver regeneration after hepatectomy. METHODS: Mice were
      placed into either a control group or a u-PA-inhibited group that received an in
      vivo u-PA inhibitor, p-aminobenzamidine. After we had removed two-thirds of the
      liver, we examined the expressions of c-jun mRNA and activated transforming
      growth factor beta 1 (TGF-beta 1), matrix metalloproteinase-2 (MMP-2) activity,
      and the level of hepatocyte and non-parenchymal cell proliferation in the two
      groups. RESULTS: In the u-PA-inhibited group, the delays in c-jun mRNA
      expression, hepatocyte proliferation, activated TGF-1 expression, and expression
      of MMP-2 activity, were 2h, 1, 2, and 1 day, respectively, and the sinusoid
      architecture was not restored by 10 days after hepatectomy. CONCLUSIONS: u-PA
      inhibition delays the expression of c-jun mRNA, hepatocyte proliferation, and
      restoration of the sinusoid architecture, suggesting that u-PA plays important
      roles in liver regeneration after hepatectomy through control of a transcription
      factor, c-jun expression.

PMID- 11983448
TI  - Steatosis is not sufficient to cause an impaired regenerative response after
      partial hepatectomy in rats.
AB  - BACKGROUND/AIMS: Fatty liver is known to be associated with increased mortality
      and morbidity after liver resection. The ability of fatty liver to regenerate
      after two-thirds partial hepatectomy was studied in three different models of
      steatosis in rats: obese Zucker rats, orotic acid-fed Wistar rats and Wistar rats
      fed a methionine-low, choline-deficient diet. METHODS: Liver regeneration was
      assessed 24 h after partial hepatectomy by bromodeoxyuridine incorporation
      (immunohistochemistry), proliferating cell nuclear antigen, cyclin E and cyclin
      dependent kinase 2 protein expression (Western blot analysis) and cyclin
      dependent kinase 2 activity (kinase assays using histone H1 as a substrate).
      RESULTS: No significant difference of proliferative response was found between
      orotic acid or methionine-low, choline-deficient diet-fed and control Wistar rats
      24 h after partial hepatectomy. In contrast, hepatocyte proliferation in obese
      Zucker rats after partial hepatectomy was significantly reduced when compared
      with their lean controls. CONCLUSIONS: Steatosis per se does not impair liver
      regeneration. The reduced liver regeneration observed in obese Zucker rats may
      not be due to fatty infiltration itself but to other factors such as leptin
      receptor dysfunction.

PMID- 11983449
TI  - Contribution of bone marrow cells to liver regeneration after partial hepatectomy
      in mice.
AB  - BACKGROUND/AIMS: We examined whether bone marrow (BM) cells can commit to liver
      consisting cells during liver regeneration after partial hepatectomy, using mice
      transplanted with green fluorescent protein (GFP) positive BM from GFP transgenic
      mice. METHODS: Partial hepatectomy or sham operation was performed. Lineage
      marker analysis of GFP positive liver cells was by immunostaining and flow
      cytometry. DiI-labeled acetylated low-density lipoprotein uptake or microsphere
      phagocytosis was examined in vitro. Lineage marker expression in BM and
      peripheral blood (PB) cells, and the vascular endothelial growth factor (VEGF)
      concentration in the liver were also examined. RESULTS: In hepatectomized mice,
      significantly more GFP positive cells participated in liver sinusoid than in sham
      operated mice, expressing CD31 but not albumin. The percentage of cells that
      incorporated acetylated low-density lipoprotein but not microspheres was 69.5+/
      3.4%, while 28.3+/-2.6% incorporated both, revealing sinusoidal endothelial and
      Kupffer cells, respectively. Increased expression of the CD31 and CD16/CD32 on
      GFP positive liver cells was also detected. The elevation of the VEGF
      concentration during liver regeneration and the increase in the CD34 and Flk-1
      expression in the liver, BM, and PB cells suggested endothelial progenitor cell
      mobilization. CONCLUSIONS: GFP cell-marking provided direct evidence of the BM
      cells participation in liver regeneration after hepatectomy, where the majority
      was committed to sinusoidal endothelial cells probably through endothelial
      progenitor cell mobilization.

PMID- 11983450
TI  - Acyclic retinoid induces partial differentiation, down-regulates telomerase
      reverse transcriptase mRNA expression and telomerase activity, and induces
      apoptosis in human hepatoma-derived cell lines.
AB  - BACKGROUND/AIMS: Acyclic retinoid (AR; all trans-3,7,11,15-tetramethyl
      2,4,6,10,14-hexadecapentaenoic acid) prevented hepatocarcinogenesis in animal
      models and in a randomized clinical trial by eradicating premalignant and latent
      malignant clones of transformed cells from the liver. We investigated the
      possible mechanism of this clonal deletion at the cellular level. METHODS: Human
      hepatoma-derived cell lines, PLC/PRF/5, HuH-7, and JHH-7, were treated in vitro
      with AR. Secretion of albumin and that of lectin-reactive isoform of alpha
      fetoprotein (AFP-L3) were measured as markers of differentiation and
      dedifferentiation of the cells, respectively. Telomerase reverse transcriptase
      (TERT) mRNA expression and telomerase activity were measured by reverse
      transcriptase polymerase chain reaction (RT-PCR) and stretch PCR assay,
      respectively. Caspase activities were measured by colorimetric protease assay.
      Mitochondrial membrane permeability transition was examined by Rhodamine
      staining. RESULTS: Production of albumin was recovered while that of AFP-L3 was
      reduced after exposure of the cells to 10 microM AR for 2 days. This
      differentiation was maintained for another 2 days without retinoid. In parallel,
      both TERT mRNA expression and telomerase activity were down-regulated. The cells
      subsequently died due to apoptosis after 4-6 experimental days. Serial increases
      in mitochondrial membrane permeability and caspase-9 and -3 activities induced
      apoptosis. CONCLUSIONS: AR first induces differentiation and reduces telomerase
      activity. Subsequent apoptosis may contribute to the eradication of the clone.

PMID- 11983451
TI  - Daily or three times a week interferon alfa-2b in combination with ribavirin or
      interferon alone for the treatment of patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Data on hepatitis C virus (HCV) viral dynamics and on the effect
      of interferon in blocking virion production have suggested a rationale for daily
      administration of interferon in patients with chronic hepatitis C infection. We
      compared the efficacy and safety of daily interferon alfa-2b in combination with
      ribavirin with those of interferon alfa-2b three times a week alone or in
      combination with ribavirin. METHODS: We randomly assigned 321 patients with
      chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in
      combination with ribavirin for 48 weeks or daily interferon alfa-2b (3 million
      units per day for 12 weeks then 3 million units three times per week for 24
      weeks) and ribavirin (36 week treatment). RESULTS: The rate of sustained
      virologic response (defined as an undetectable serum HCV-RNA level 72 weeks after
      initiation of treatment) was higher in patients who received combination therapy
      with three times weekly interferon (51.7%) or daily interferon (46.1%) than in
      patients who received interferon alone (25%) (P=0.0001 and P=0.002,
      respectively). Independent predictive factors for sustained virologic response
      were combination therapy, weight, genotype and viral load. In conclusion, in
      patients with chronic hepatitis C, combination therapy with induction treatment
      (daily interferon for 12 weeks) and shorter duration of treatment was not
      different from combination therapy for 48 weeks without induction treatment.
      CONCLUSIONS: Induction treatment with interferon for 12 weeks and combination
      therapy for a total duration of 36 weeks could therefore be cost effective.

PMID- 11983452
TI  - The evolution of hepatitis B virus serological patterns and the clinical
      relevance of isolated antibodies to hepatitis B core antigen in HIV infected
      patients.
AB  - BACKGROUND/AIMS: The evolution of hepatitis B virus (HBV) serological patterns
      and the clinical relevance of isolated anti-HBc pattern are not well established
      in HIV infected patients. METHODS: A cohort of 240 patients was followed for
      6.9+/-3.4 years, with iterative HBV serologic assays performed (mean interval of
      2.2 years). RESULTS: Five patients without HBV markers at baseline subsequently
      developed positive anti-HBs (incidence 0.66/100 patient-year), as did two
      patients with chronic HBs antigenemia (incidence 1.66/100 patient-year). Only one
      patient with isolated anti-HBc pattern developed HBs chronic antigenemia.
      Persistent isolated anti-HBc pattern was observed in 37 patients (13 with
      detectable blood HBV DNA) and was strongly associated with positive hepatitis C
      virus (HCV) viremia (hazard ratio=9.5, confidence interval 95%: 4.5-20.0,
      P<0.0001). Hepatic lesions were more severe in HCV infected patients with
      persistent isolated anti-HBc pattern than in those without (Knodell score 9.2+/
      4.6 versus 6.7+/-5.0, P=0.04). In time updated analysis, this pattern was not
      associated with an increased risk of hepatotoxicity, by contrast with HCV
      infection or positive HBs antigenemia. CONCLUSIONS: In HIV infected patients, HBV
      serological status must be systematically and regularly assessed, and systematic
      HBV vaccination must be proposed in those without HBV marker. Isolated anti-HBc
      pattern must be considered in the management of hepatitis C, but not for
      antiretroviral therapy.

PMID- 11983453
TI  - Accelerated hepatic fibrosis in patients with combined hereditary hemochromatosis
      and chronic hepatitis C infection.
AB  - BACKGROUND/AIMS: Hereditary hemochromatosis (HH) and chronic hepatitis C virus
      (HCV) infection can both result in hepatic fibrosis and cirrhosis. It has been
      proposed that iron overload and HCV may have potentiating effects on hepatic
      fibrogenesis. This study determined if HH patients with HCV would present with
      hepatic fibrosis/cirrhosis at a younger age and at a lower hepatic iron
      concentration compared to patients with HH or HCV alone. METHODS: Ten patients
      with combined HCV and HH were compared to 13 patients who had HH alone and 24
      patients who had HCV alone. All patients had advanced fibrosis/cirrhosis on liver
      biopsy. All HH patients were homozygous for the C282Y mutation. RESULTS: At
      presentation with advanced fibrosis/cirrhosis, the mean age of the HH/HCV group
      was significantly lower than that of the HH group and the HCV group. The mean
      hepatic iron concentration was lower in the combined HH/HCV group compared to
      that of the HH group. CONCLUSIONS: HH patients with HCV present with advanced
      fibrosis/cirrhosis at a younger age and at a lower hepatic iron concentration
      compared to HH patients without HCV. These findings support the concept that the
      combination of HH-induced iron overload and HCV has a potentiating effect on
      hepatic fibrogenesis.

PMID- 11983454
TI  - Small duct primary sclerosing cholangitis.

PMID- 11983455
TI  - Liver regeneration: with a little help from marrow.

PMID- 11983456
TI  - Progressive reversion of clinical and molecular phenotype in a child with liver
      mitochondrial DNA depletion.
AB  - Mitochondrial DNA depletion is a well established cause of severe liver failure
      in infancy. The autosomal inheritance of this quantitative mitochondrial DNA
      defect supports the involvement of a nuclear gene in the control of mitochondrial
      DNA level. We previously described a case of a 28-month-old child presenting with
      a progressive liver fibrosis due to a mitochondrial DNA depletion (85% at 12
      months of age). As this syndrome was clinically liver-restricted, a liver
      transplant was initially discussed. We report the clinical, biochemical and
      molecular follow-up of this child, now 6 years old. The patient displayed a
      spontaneous gradual improvement of his liver function with continuous increment
      of clotting factor values since 32 months of age. A marked reduction of the
      previous extensive fibrosis was evidenced on a liver biopsy performed at 46
      months of age associated with a dramatic decrease of the mitochondrial DNA
      depletion (35%). Consequently, an almost complete restoration of respiratory
      chain activities containing mitochondrial DNA-encoded subunits was observed. This
      is the first report of a revertant phenotype in liver mitochondrial DNA depletion
      syndrome.

PMID- 11983457
TI  - Poststenotic dilatation and helical flow in the umbilical portion of the portal
      vein.

PMID- 11983458
TI  - Amantadine: a different approach.

PMID- 11983459
TI  - Crigler-Najjar syndrome type II in a caucasian patient resulting from two
      mutations in the bilirubin uridine 5'-diphosphate-glucuronosyltransferase
      (UGT1A1) gene.

PMID- 11983460
TI  - Danazol-induced hepatocellular adenoma in patients with hereditary angio-oedema.

PMID- 11983465
TI  - Evaluation of odontogenic maxillary sinusitis after conservative therapy using CT
      and bone SPECT.
AB  - Fifteen patients with odontogenic maxillary sinusitis examined using computed
      tomography (CT) and single photon emission computed tomography bone scintigraphy
      (bone SPECT) were reviewed. The changes in bone activity associated with
      causative maxillary alveolitis, evaluated by bone SPECT, before and after
      conservative therapy were correlated with the pathologic changes in the maxillary
      sinus mucosa and ostium demonstrated on CT images following conservative therapy.
      This combination of imaging methods is valuable for predicting the prognosis and
      selecting appropriate treatments for the disease.

PMID- 11983466
TI  - Contrast-enhanced high in-plane resolution dynamic MRI of the breast. Are there
      advantages in comparison to standard dynamic MRI?
AB  - OBJECTIVE: To evaluate the diagnostic advantages of high in-plane resolution
      contrast-enhanced (CE) magnetic resonance imaging (MRI) of the breast in
      comparison to standard CE-MRI. METHODS: Forty-one patients with 51
      hypervascularized lesions were selected prospectively after undergoing bilateral
      standard CE MRI (slice thickness 4 mm, in-plane resolution 1.52 x 1.25 mm2,
      temporal resolution 81 s). Patients underwent high in-plane resolution CE MRI,
      either (n=21) a two-dimensional fast-low-angle-shot sequence (slice thickness 4
      mm, in-plane resolution 0.76 x 0.63 mm2, temporal resolution 96 s) or (n=20) a SE
      sequence being used (slice thickness 4 mm, in-plane resolution 0.8 x 0.63 mm2,
      temporal resolution 115 s). RESULTS: Histopathology revealed 33 malignant and 18
      benign lesions (0.2-2.2 cm). Morphologic characteristics were much better
      visualized with high in-plane resolution. Additional diagnostic information,
      however, resulted only in one patient with fibroadenoma due to a better
      visualization of smooth contours. CONCLUSIONS: High in-plane resolution provides
      better visualization of morphologic patterns in comparison to standard dynamic
      MRI. However, a diagnostic advantage is only rare.

PMID- 11983467
TI  - Granulocytic sarcoma. Cranial and breast involvement.
AB  - The term granulocytic sarcoma designates an infrequent solid tumor composed of
      aggregates of immature granulocytic precursors in extramedullary sites. The
      lesion generally occurs either during the natural course of acute myelogenous
      leukemia or after a remission has been achieved; however, it may rarely represent
      the initial manifestation of the disease. We present radiologic features of
      cranial and breast involvement of granulocytic sarcoma in a 13-year-old female
      with acute myelogenous leukemia. The cranial lesion appeared nearly isointense
      with cortical gray matter on T1- and T2-weighted magnetic resonance (MR) images,
      and enhanced homogeneously after the injection of gadolinium. MRI showed a well
      delineated lobulated mass in the left breast, which had a heterogeneous
      hyperintense signal and remarkable contrast enhancement.

PMID- 11983468
TI  - MR findings in cardiac hydatid cyst.
AB  - We report a case of a 23-year-old man with a cardiac hydatid cyst involving the
      left ventricle wall. The diagnosis of the cyst was obtained by magnetic resonance
      (MR) imaging. He was operated on for cardiac hydatid cyst using enucleation and
      capitonnage procedure under extracorporeal circulation. Histopathologic study
      confirmed hydatid cyst diagnosis.

PMID- 11983469
TI  - Changes in hepatic perfusion after administration of hydroxyethyl starch in
      intensive care patients assessed using color-coded Doppler sonography.
AB  - Using color-coded Doppler sonography (CCDS), changes in the resistance index of
      the hepatic artery (HA-RI) and in the velocities of the hepatic artery, portal
      and splenic vein (HA-V, PV-V, SV-V) were measured after administration of
      hydroxyethyl starch (HES) in 50 intensive care patients. PV-V and SV-V increased,
      whereas HA-V and HA-RI remained unchanged. CCDS is suitable to assess liver
      perfusion in intensive care patients. Since HES enhances splanchnic perfusion,
      its application improves hepatic perfusion in intensive care patients.

PMID- 11983470
TI  - Diagnosis and staging of gallbladder carcinoma. Evaluation with dynamic MR
      imaging.
AB  - The purpose of this study is to determine the ability of dynamic magnetic
      resonance imaging (MRI) in the diagnosis and staging of gallbladder cancer (GBC).
      Images of dynamic MRI of hepatobiliary system combined with MR cholangiography
      (MRC) of 18 patients with pathologically proved gallbladder cancer were
      correlated with pathological and operative findings. Focal or diffuse wall
      thickening was present in 10 patients. In five patients, the tumor appeared as a
      fungating or intramural mass. A tumor replacing the gallbladder was found in two
      patients and a small cancer in cystic duct in one patient. The tumor featured
      early and irregular enhancement, which persisted throughout the dynamic study.
      Metastatic nodes were found by surgicopathology in 13 patients and were depicted
      by the dynamic MRI in 11 patients. Local invasion to liver was found by surgery
      in 12 patients and correctly detected by MRI in 11 patients. MRI detected
      duodenum invasion in three out of six patients and none of the three cases with
      omental metastasis. In conclusion, dynamic MRI is useful and reliable in staging
      of advanced gallbladder cancer. MRI combined with MRC is sensitive in detection
      of obstructive jaundice, liver invasion as well as liver and lymph nodes
      metastasis. It is more difficult to delineate the invasion to duodenum and
      omental metastasis by MRI.

PMID- 11983471
TI  - Pediatric focal xanthogranulomatous pyelonephritis: dynamic contrast-enhanced MRI
      findings.
AB  - Xanthogranulomatous pyelonephritis (XPN) is the result of chronic renal
      infection. It is very rare in childhood and the focal form, which is said to be
      more common in children, is often misdiagnosed as a renal tumor. We report a case
      of a focal XPN in a 14-year-old girl. The true preoperative diagnosis may be very
      hard in children especially in the focal form but it seems to be possible by the
      help of dynamic contrast-enhanced MRI.

PMID- 11983472
TI  - Pedicular stress fracture in lumbar spine.
AB  - The purpose of this article is to report two cases of pedicular stress fracture
      of the lumbar spine, which is an uncommon cause of low back and leg pain. The
      relevant literature is reviewed and features of the cases that differ from those
      already reported are highlighted. One of our cases of pediculolysis is the first
      in the literature for that is caused by rotational instability induced by
      laminectomy. The remodeling of the fractured pedicle was striking when compared
      with its normal counterpart. To the authors' knowledge, this is the first report
      of a pediculolysis with T2-weighted imaging findings. In addition, we report the
      computed tomographic (CT) and magnetic resonance (MR) imaging findings of a
      healed pediculolysis that has not been reported previously.

PMID- 11983473
TI  - Knee chondrocalcinosis: an ultrasonographic study of the hyalin cartilage.
AB  - PURPOSE: The purpose of the present research was to test the diagnostic value of
      ultrasonography (US) to detect chondrocalcinosis in the hyalin cartilage (HC).
      METHOD: This was tested on both knees of 21 selected patients with a history of
      unilateral HC and 19 controls. In Group, I (US), evaluation was performed on
      selected knees. The selection was based on the evidence of HC on previous
      radiographs. In Group II, US examination of the contralateral side of the same
      cohort was performed first and radiographic picture was done as a second step.
      RESULTS: Ultrasonically, detectable calcification was present in 17 of 21 in
      Groups I and II, respectively. The US findings of the latter were confirmed on
      radiographs in 15. The sensitivity and specificity of Groups I and II were 80
      100% and 89-91%, respectively. The overall sensitivity and specificity of US in
      calcification verification in HC proved to be 89% and 90%. Popliteal cyst was
      detected in 10 cases of which 8 showed evidence of calcification in the bursal
      fluid. Typical calcium pyrophosphate dihydrate (CPPD) crystals could be
      demonstrated in five of those. CONCLUSION: US is a valuable, sensitive and
      specific method in the evaluation of patients with chondrocalcinosis and crystal
      deposition disease.

PMID- 11983474
TI  - The spectrum of radiographic findings in primary hyperparathyroidism.
AB  - The aim of this study was to assess the spectrum of radiographic findings in
      primary hyperparathyroidism (PHPT). The study group consisted of 16 women and 7
      men whose Ca levels were at least two or three times higher than normal. The
      average age was 55.3 in women and 49.4 in men. We detected carcinoma in 1,
      hyperplasia in 1, multiple adenomas in 4, single adenoma in 17 patients. The most
      common finding in the skeletal system was the decreased bone mineral density
      (BMD) and the complete loss of the lamina durae dentium. BMD was found lower in
      women than in men. This result attributed the increased number of postmenopausal
      patients in our study group. The second most common finding in our study group
      was subperiosteal bone resorption. Brown tumors (BTs) were located at maxilla in
      one, widespread in one, mandibula in two, long tubular bones in four patients.
      Renal stone disease was found in five, spastic colon in two, gastric ulcer in
      one, mitral valve calcification in one patients. We demonstrated no pathologic
      changes consistent with PHPT in remaining seven patients.

PMID- 11983475
TI  - Soft tissue uptake of Tc99m-MDP in acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is associated rarely with hypercalcemia. This
      may be due to elevated levels of parathyroid hormone-related peptide (PTHrP). We
      report a case of an 18-year-old female patient who was presented with a
      pathological fracture of left intertrochanteric region. Bone scintigraphy was
      consistent with features of hypercalcemia associated with metastatic
      calcification. A bone marrow biopsy led to the diagnosis of ALL. The mechanism of
      hypercalcemia in ALL, metastatic calcification and soft tissue uptake of bone
      seeking agents in this case are discussed in detail.

PMID- 11983476
TI  - Spontaneous rupture of the tibialis anterior tendon in a patient with psoriasis.
AB  - A very rare case of spontaneous rupture of the tibialis anterior tendon diagnosed
      by MR imaging is presented. The tendon rupture occurred in a patient with recent
      onset psoriasis of both shins who used a corticosteroid cream (0.1% of
      methylprednisolone aceponate) for his skin lesions during the last 3 months
      before the incident causing tendon rupture. This is the first report of a
      spontaneous tendon rupture in a patient with psoriasis.

PMID- 11983477
TI  - STIR sequence in infectious sacroiliitis in three patients.
AB  - Magnetic resonance imaging (MRI) provides the most detailed evaluation of the
      sacroiliac (SI) joint and surrounding soft tissue. Therefore, this technique
      represents the most sensitive and specific method in early diagnosis of
      infectious sacroiliitis. Among three patients diagnosed as having infectious
      sacroiliitis in our hospital, the short tau inversion recovery sequence (STIR)
      was found to be more effective than the T1 contrast-enhanced sequence,
      particularly in delineating all findings of the SI joint inflammation and
      allowing for the early detection of septic sacroiliitis.

PMID- 11983484
TI  - Genomic and nongenomic effects of estrogens: molecular mechanisms of action and
      clinical implications for male reproduction.
AB  - Although estrogens have been always referred as female hormones, the deep
      involvement of these steroids in the development and control of male reproductive
      functions is only recently emerging. After a brief overview of estrogen effects
      on male different systems and organs, the present review will focus on estrogens
      as potential hormones in male reproduction. The present knowledge on the
      structure and regulation of estrogen receptor (ER) genes will be summarized and
      the expression pattern of the different isoforms of ERs in male reproductive
      system and of aromatase (Ar), the enzyme responsible for conversion of androgens
      into estrogens, will be reported, paying particular attention to distribution in
      human tissue. In addition to the description of the well-known genomic action
      exerted by estrogens through the classical nuclear receptors, alternative
      intracellular mechanisms of action of these hormones will be reviewed, with
      particular attention to the recently described so called nongenomic ones. In
      particular, recent data supporting evidences of nongenomic action of estrogens on
      human spermatozoa will be discussed. Possible cross-talks between the different
      signaling pathways will be taken into account. Comparison between phenotype in
      knockout mice for the genes encoding ERs and Ar and patients carrying congenital
      estrogen deficiency due to inactivating mutations of Ar gene or to estrogen
      resistance has been of fundamental importance in our understanding of the role of
      estrogens in male fertility. Finally, the requirement of estrogens in
      physiological development of male reproductive system will be described pointing
      out the possible deleterious effects on male reproductive structures exerted by
      abnormal exposure of male fetuses and adults to these hormones.

PMID- 11983485
TI  - The upstream stem-loop domain of the 3' untranslated region of apolipoprotein II
      mRNA binds the estrogen-regulated mRNA stabilizing factor.
AB  - Apolipoprotein II (apoII), a component of the very low density lipoprotein (VLDL)
      particle, is a yolk protein expressed in the liver in response to estrogen. Its
      expression is modulated by estrogen-mediated stimulation of transcription as well
      as stabilization of its mRNA. This stabilization is due to the estrogen-regulated
      mRNA stabilizing factor (E-RmRNASF) [Cell. Mol. Biol. Res. 41 (1995) 583). E
      RmRNASF protects apoII mRNA from targeted endonucleolytic degradation. The
      expression of E-RmRNASF itself is under estrogenic control. The hepatic
      expression of E-RmRNASF is also modulated by certain estrogenic and anti
      estrogenic non-steroidal environmental xenobiotics [Biochem. Pharmacol. 53 (1997)
      1425]. Studies involving RNA affinity-based depletion of mRNA stabilization
      activity indicated that E-RmRNASF binds to apoII mRNA. E-RmRNASF binds apoII mRNA
      in a region-specific manner. The region of binding has been narrowed down to the
      upstream domain of stem-loop secondary structure spanning nucleotides (nt) 402
      558 in the 3' untranslated region (3'UTR). A RNA affinity chromatography
      procedure using this portion of apoII mRNA was utilized for the purification of E
      RmRNASF. A gel filtration (GF) chromatography step preceding the RNA affinity
      chromatography was required for additional enrichment of E-RmRNASF. A functional
      assay involving the in vitro stabilization of apoII mRNA from degradation was
      utilized to detect E-RmRNASF during chromatography. E-RmRNASF appears to be a
      protein of apparent molecular weight of 20-25kDa visualized by SDS polyacrylamide
      gel electrophoresis.

PMID- 11983486
TI  - Glucocorticoid receptor binding in twin pairs is affected by shared environment
      but not by shared genes.
AB  - We set out to determine whether glucocorticoid receptor activity is affected
      mainly by genetic or environmental factors. The affinity and capacity of the
      glucocorticoid receptor was measured using dexamethasone binding in whole
      leukocytes from 53 monozygotic and 48 dizygotic twin pairs. Receptor binding
      characteristics assayed from twin pairs on the same day were highly correlated
      within twin pairs irrespective of zygosity. Apparent Kd was negatively correlated
      with environmental temperature (R(2)=0.13, P<0.0001) but this did not confound
      the intra-pair correlation, suggesting a strong familial component independent of
      zygosity. Receptor binding parameters were not more closely correlated in
      monozygotic twins than dizygotic twin pairs indicating that there is no major
      genetic contribution to receptor binding and that environmental influences
      predominate. The close similarity in binding between twin pairs in adulthood
      raises the possibility that familial, non-genetic, factors such as shared early
      life environment may programme the glucocorticoid receptor.

PMID- 11983487
TI  - Tamoxifen elicits its anti-estrogen effects in growth plate chondrocytes by
      inhibiting protein kinase C.
AB  - 17 beta-Estradiol (E(2)) regulates growth plate cartilage cells via classical
      nuclear receptor mechanisms, as well as by direct effects on the chondrocyte
      membrane. These direct effects are stereospecific, causing a rapid increase in
      protein kinase C (PKC) specific activity, are only found in cells from female
      rats and are mimicked by E(2)-bovine serum albumin (BSA), which cannot penetrate
      the cell membrane. E(2) and E(2)-BSA stimulate alkaline phosphatase specific
      activity and proteoglycan sulfation in female rat costochondral cartilage cell
      cultures, but traditional nuclear receptors do not appear to be involved. This
      study examined the effect of the anti-estrogen tamoxifen on these markers of
      chondrocyte differentiation; the gender-specificity of tamoxifen's effect on PKC,
      if tamoxifen has an effect on vitamin D metabolite-stimulated PKC, which is
      mediated via specific membrane receptors (1,25-mVDR; 24,25-mVDR) and whether the
      effect of tamoxifen is mediated by nuclear estrogen receptors. Tamoxifen dose
      dependently inhibited the effect of E(2)-BSA on PKC, alkaline phosphatase and
      proteoglycan sulfation in confluent cultures of female resting zone (RC) cells
      and growth zone (GC) (prehypertrophic/upper hypertrophic zones) cells, suggesting
      that its action is at the membrane and not cell maturation-dependent. Neither the
      estrogen receptor (ER) antagonist ICI 182780 nor the ER agonist
      diethylstilbesterol affected E(2) or E(2)-BSA-stimulated PKC in female
      chondrocytes. Tamoxifen also inhibited the increase in PKC activity due to 1
      alpha,25-(OH)(2)D(3) or 24R,25-(OH)(2)D(3) in growth plate cells derived from
      either female or male rats. Inhibition of PKC by tamoxifen may be a general
      property of membrane receptors involved in rapid responses to hormones.

PMID- 11983489
TI  - Synthesis and biochemical evaluation of novel and potent inhibitors of the enzyme
      oestrone sulphatase (ES).
AB  - In an effort to investigate the structural requirements for the inhibition of the
      enzyme oestrone sulphatase (ES), we have previously undertaken extensive
      structure-activity relationship studies. Using the data from molecular modelling
      and structure-activity relationship determination studies, we have designed a
      number of compounds based upon 4-sulphamated phenyl ketones. Here, we report the
      results of our study into a series of these compounds as potential inhibitors of
      ES. The results of the study show that these compounds are potent inhibitors the
      possessing greater inhibitory activity than 4-methylcoumarin-7-O-sulphamate
      derivative (COUMATE) (a potent non-steroidal inhibitor), but are weaker than
      oestrone-3-sulphamate (EMATE) and the recently reported 667- and 669-COUMATE,
      however, they provide good lead compounds in the search for potent inhibitors of
      ES. Furthermore, the compounds are observed to be irreversible inhibitors. From
      the consideration of the structure-activity relationship of these novel
      compounds, we have attempted to rationalise the significance of the log P factor
      in the inhibition of ES and suggest that a log P requirement of approximately 3.5
      aids the inhibition through the rapid expulsion of the carbon backbone from the
      active site. We also propose that the same factor is responsible for the
      hydrolysis of oestrone sulphate reaction, appearing to be an irreversible
      process.

PMID- 11983488
TI  - Short-term effects of anastrozole treatment on insulin-like growth factor system
      in postmenopausal advanced breast cancer patients.
AB  - Insulin-like growth factors (IGFs) play a fundamental role in cancer development
      by acting in both an endocrinal and paracrinal manner, and hormone breast cancer
      treatments affect the IGF system by modifying circulating growth factor levels.
      We evaluated total IGF-1, IGF-2, IGF binding protein (IGFBP)-1 and IGFBP-3 in the
      blood of 34 postmenopausal advanced breast cancer patients (median age 63 years,
      range 41-85) treated with anastrozole, a non-steroidal structure aromatase
      inhibitor (NSS-AI). The plasma samples were obtained at baseline, and after 2, 4,
      8 and 12 weeks of treatment. The IGFs were quantitated by means of sensitive
      radioimmunoassays (RIAs). IGF-1 significantly increased during anastrozole
      treatment (baseline versus 12 weeks, P=0.031), IGF-2 showed a trend towards an
      increase, and IGFBP-1 constantly but not significantly decreased; IGFBP-3 did not
      seem to be affected at all. The anastrozole-induced changes in IGFs and IGFBP-1
      appeared to be different in the patients receiving a clinical benefit from those
      observed in non-responders. We have previously shown that letrozole (a different
      type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the
      biological effects of anastrozole on the components of the IGF system confirm our
      previous observations.

PMID- 11983490
TI  - Evidence for the mechanism of the irreversible inhibition of oestrone sulphatase
      (ES) by aminosulphonate based compounds.
AB  - In our search for the mechanism of the enzyme oestrone sulphatase (ES) we have
      synthesised and evaluated a number of compounds that were predicted to possess
      some inhibitory activity. Some of these compounds were indeed found to be
      inhibitors of ES, whilst other compounds were not. From a consideration of the
      structure-activity relationship (SAR) of the inhibitors and non-inhibitors of
      this enzyme, we discovered a factor which we now believe is the main inhibitory
      moiety within the aminosulphonated inhibitors. We therefore report the results of
      our study into a series of phenyl and alkyl sulphamated compounds as inhibitors
      of ES. The results of the study show that the substituted phenyl sulphamates are
      potent inhibitors, whereas the alkyl compounds are, in general, non-inhibitors.
      Using the results of our SAR study, we postulate the probable mechanism for the
      irreversible and reversible inhibition of ES, and rationalise the role of the
      different physicochemical factors in the inhibition of this crucial enzyme.

PMID- 11983491
TI  - Glycyrrhizic acid suppresses type 2 11 beta-hydroxysteroid dehydrogenase
      expression in vivo.
AB  - Licorice-derivatives such as glycyrrhizic acid (GA) competitively inhibit 11 beta
      hydroxysteroid dehydrogenase(11 beta-HSD) type 2 (11-HSD2) enzymatic activity,
      and chronic clinical use often results in pseudoaldosteronism. Since the effect
      of GA on 11-HSD2 expression remains unknown, we undertook in vivo and in vitro
      studies. Male Wistar rats were given 30, 60 or 120 mg/kg of GA twice a day for 2
      weeks. Plasma corticosterone was decreased in those given the 120 mg dose, while
      urinary corticosterone excretion was increased in those given the 30 and 60 mg
      doses but decreased in those given 120 mg GA. NAD(+)-dependent dehydrogenase
      activity in kidney microsomal fraction was decreased in animals receiving doses
      of 60 and 120 mg GA. The 11-HSD2 protein and mRNA levels were decreased in those
      given 120 mg GA. In contrast, in vitro studies using mouse kidney M1 cells
      revealed that 24h treatment with glycyrrhetinic acid did not affect the 11-HSD2
      mRNA expression levels. Thus, in addition to its role as a competitive inhibitor
      of 11-HSD2, the chronic high dose of GA suppresses mRNA and protein expression of
      11-HSD2 possibly via indirect mechanisms. These effects may explain the prolonged
      symptoms after cessation of GA administration in some pseudoaldosteronism
      patients.

PMID- 11983492
TI  - Distribution and metabolism of topically applied progesterone in a rat model.
AB  - This study investigated the transdermal uptake and subsequent tissue distribution
      of [(3)H]progesterone applied in a commercially available progesterone cream in a
      rat model. Concentrations of lipid- and water-soluble metabolites of
      [(3)H]progesterone were also measured in plasma, urine and selected tissues
      (uterus, liver, kidney, salivary gland) 3 h after its topical application. Female
      rats were ovariectomized and adrenalectomized to remove all endogenous
      progesterone, and 4 weeks later were anaesthetized and 150 mg Pro-Feme cream
      (containing progesterone 3.2% w/w and 200 microCi [(3)H]progesterone) was applied
      to the abdominal skin. Six arterial blood samples were then obtained from a
      carotid cannula over the following 3h, and urine and selected tissue samples were
      collected after the final blood sample. Plasma progesterone increased
      progressively until 90 min, then remained relatively stable. Plasma levels of
      [(3H)]progesterone were high by the 15-min sample and increased only slightly
      thereafter. Water-soluble metabolites were detectable in plasma at 15 min,
      whereas lipid-soluble metabolites became apparent only by 60 min then increased
      progressively to 180 min. The tissue:plasma concentration ratio for
      [(3)H]progesterone exceeded 1 in all tissues, most notably in uterus (8.4) and
      lung (9.6), whereas urinary [(3)H]progesterone levels were only half those in
      plasma. Concentrations of lipid- and water-soluble progesterone metabolites were
      most prevalent in liver and kidney, and both reached very high concentrations in
      urine. These results demonstrate that topically applied progesterone is rapidly
      absorbed transdermally and that its patterns of distribution and metabolism are
      comparable to those previously reported for intravascularly administered
      progesterone.

PMID- 11983493
TI  - Effects of estradiol and estradiol sulfamate on the liver of ovariectomized or
      ovariectomized and hypophysectomized rats.
AB  - This study was performed to evaluate and compare the effects of estradiol
      sulfamate (J995) and estradiol (E2) on the hepatic levels of the estrogen
      receptor (ER) and its mRNA, in ovariectomized (OVX) and OVX+hypophysectomized
      (OVXHX) female rats and to study the effects on the liver-derived serum compounds
      angiotensin I, triglycerides, high-density lipoprotein (HDL) and cholesterol. ER
      concentrations were determined using ligand-binding assay (LBA) and enzyme immuno
      assay (EIA), and the mRNA levels using solution hybridization. The rats were
      treated orally (p.o.) or subcutaneously (s.c.) for 7 days, with treatments
      initiated 14 days after surgery. No differences were found in ER mRNA levels
      between J995 and E2 treated rats. The s.c. administered estrogens increased ER
      levels in OVX rats. Addition of GH+DEX to OVXHX rats restored the ER to levels
      above those seen in intact rats, whereas simultaneous oral treatment with E2
      significantly decreased ER levels again. The s.c. treatment with either J995 or
      E2 limited the increase caused by addition of GH+DEX. After oral treatment
      angiotensin I levels were increased by E2, but not by J995, while triglycerides,
      HDL and cholesterol levels were decreased by oral E2, J995 showing a similar
      pattern but was less effective. In summary, these results on hepatic ER levels
      and estrogen dependent compounds produced by the liver showed that J995 has a
      lower impact on the normal liver functions after oral treatment than E2. Thus,
      J995 is a very promising substance for development of oral estrogen treatment
      with reduced hepatic side effects.

PMID- 11983494
TI  - Distribution and metabolism of 20 alpha-hydroxylated progestins in the female
      rat.
AB  - The C21 steroids, progesterone and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha
      DHP) play pivotal roles in the initiation, timing and maintenance of ovulatory
      function and pregnancy in female mammals. They also have growth factor and
      central nervous system (CNS) effects; some of these are non-genomic effects
      mediated through 5 alpha-reduced and 3 alpha-hydroxylated derivatives. These
      studies examined the in vivo uptake and conversion of 20 alpha-DHP in selected
      CNS sites and peripheral tissues after injection of [(3)H]-20 alpha-DHP. The
      effects of steroid mass, time after injection, and ovariectomy, adrenalectomy and
      estradiol treatment were assessed in the pineal gland, preoptic area of the
      hypothalamus (POA), medial basal hypothalamus (MBH), midbrain, cerebellum,
      cerebral cortex, anterior pituitary (AP), uterus and skeletal muscle. Tissue
      extracts were analyzed by scintillation counting and chromatography to quantify
      and localize 20 alpha-DHP and its 5 alpha-reduced derivatives. Injection of
      increasing mass of [(3)H]-20 alpha-DHP to ovariectomized/adrenalectomized
      (ovx/adx) rats results in a linear increase in (3)H-steroid 10 min post injection
      in all tissues. (3)H-steroid content increases with time over 1 h post injection
      in the pineal, AP and uterus. Tissue differences in (3)H-steroid level are
      observed with higher levels in pineal, MBH, POA, AP and midbrain than in cerebral
      cortex and cerebellum, and in uterus, ovary and adrenal than in muscle.
      Ovariectomy, adrenalectomy and estradiol treatment affect (3)H-steroid levels in
      a tissue dependent manner, and the metabolites of 20 alpha-DHP in MBH and AP
      differ between groups. The findings demonstrate that target tissues, including
      areas of the CNS, are able to selectively take up and retain 20 alpha-DHP, and
      also support a physiological role for this progestin and its metabolites in
      modulation of CNS and reproductive functions.

PMID- 11983495
TI  - Rotational foot placement specifies the lever arm of the ground reaction force
      during the push-off phase of walking initiation.
AB  - The lever arm of the ground reaction force (GRF) about the talocrural joint axis
      is a functionally important indicator of the nature of foot loading. Walking
      initiation experiments (ten subjects; age, 23-29 years) were completed to
      demonstrate that rotational foot placement is a possible strategy to specify the
      lever arm. Externally-rotated foot placement resulted in larger lever arms during
      push-off. A computer simulation of push-off revealed that a decreased lever arm
      reduces the plantarflexion moment necessary to maintain a constant forward
      velocity, while increasing the required plantarflexion velocity. Shortening of
      the foot thus diminishes the muscular force demand but also requires high muscle
      fiber shortening velocities that may limit the force generating capacity of
      plantar flexors. Decreased plantar flexion moment and slow walking previously
      noted in partial-foot amputees may result from shortened lever arms in this
      manner.

PMID- 11983496
TI  - A model for lever-arm length calculation of the flexor and extensor muscles at
      the ankle.
AB  - A sagittal-plane mathematical model of joint mobility, including the mechanical
      effect of the extensor retinacula, was used to predict the lever arm lengths of
      the main flexor and extensor muscles of the human ankle over the range of
      movement. In plantarflexion, the centre of rotation lies posteriorly and
      distally, maximising the lever arm of the tibialis anterior. The action of the
      gastrocnemius and soleus is maximised in dorsiflexion. Traditional calculation of
      ankle joint moment based on a fixed centre of rotation is acceptable only in
      exercises such as level walking with a limited range of motion about the neutral
      position. The present model with a moving centre is particularly advised in
      exercises which take the joint nearer to the extremes of sagittal motion.

PMID- 11983497
TI  - Longitudinal profiles of oxygen uptake during treadmill walking in able-bodied
      children: the locomotion energy and growth study.
AB  - The purpose of this study was to document age-related changes in walking V(O(2))
      in able-bodied boys and girls. Beginning at age 6 and ending at age 10, 23
      children (14 girls, 9 boys) performed six 5-min bouts of level treadmill walking
      at 0.67, 0.89, 1.12, 1.34, 1.56, and 1.79 m s(-1) on an annual basis. Prior to
      data collection, subjects received 60 min of treadmill walking practice. During
      the last 2 min of each walking bout, a 2-min sample of expired air was collected
      in a meteorological balloon and analyzed to determine V(O(2)). Averaged across
      age, interindividual variation in V(O(2)) ranged from 32 to 41%. Repeated
      measures analysis of variance demonstrated a speed by age interaction for
      V(O(2)), such that mean V(O(2)) rose (P< or = 0.05) across the five fastest
      speeds for 6-, 7-, 8-, and 10-year olds and increased over the entire speed range
      for 9-year olds. For all speeds, V(O(2)) decreased yearly from the ages of 6 to
      8. When averaged across speeds, V(O(2)) was 27% higher for 6-year olds compared
      with 10-year olds. From a clinical perspective, access to longitudinal
      measurements of walking V(O(2)) in able-bodied children should be helpful in
      interpreting gait energy use in children with movement disorders and evaluating
      treatment strategies designed to reduce the aerobic demand of locomotion in youth
      with impaired mobility.

PMID- 11983498
TI  - Age-related changes in the interactive mobility of the hip and knee joints: a
      geometrical analysis.
AB  - This study examined any systematic age-related change in the passive range of
      motion (PROM) of the hip and knee joints. Seventy-seven healthy male volunteers
      ranging in age from 15 to 73 years were assessed. A geometrical range of motion
      (ROM) analysis was applied, which could evaluate the effects of both
      monoarticular and biarticular muscles. The PROM of the hip joint decreased
      progressively with advancing age, whereas that of the knee joint remained
      unchanged. In addition, the interactive PROM of the hip and knee joint associated
      with biarticular rectus femoris and hamstring muscles also showed an age-related
      reduction. The progressive reduction of the ROM is probably caused by shortening
      of muscles or connective tissues due to reduced compliance of joint structures
      and degenerative changes in spinal alignment, as well as by diminished muscle
      stretching resulting from a decrease in daily physical activities with advancing
      age.

PMID- 11983499
TI  - Mechanisms of disturbed motor control in ankle weakness during gait after stroke.
AB  - This study investigated the role of paresis, excessive antagonist coactivation,
      increased muscle-tendon passive stiffness and spasticity in the reduced stance
      phase plantarflexor moment (Mmax) and swing phase dorsiflexion during gait
      (DFmax) in subjects with a recent (<6 months post-stroke) hemiparesis (patients).
      The gait pattern of the paretic and non-paretic sides was evaluated in 30
      patients (aged 57.8+/-10.8 years), whereas only one side was evaluated in 15
      healthy controls (aged 59.1+/-9.8 years) while walking at natural and very slow
      speeds. Peak plantarflexor moment (Mmax) and peak medial gastrocnemius (MG)
      activation during the stance phase, as well as peak dorsiflexion angle (Dfmax)
      and peak tibialis anterior (TA) activation during the swing phase, were retained
      for analysis. In addition, a coactivation index and a plantarflexor spasticity
      index were calculated for both the stance and the swing phase, and plantarflexor
      passive stiffness was evaluated on an isokinetic dynamometer. The results showed
      that Mmax on the paretic and non-paretic sides were both reduced compared with
      control values at natural speed. This reduction was combined to a low MG
      activation (paresis) on the paretic side. On the non-paretic side, the reduced
      plantarflexor moment was related to excessive coactivation levels. The swing
      phase Dfmax tended to be reduced (not significantly) on the paretic side of the
      patients compared with control values. This reduction was neither associated with
      excessive antagonist coactivation nor to plantarflexor hyperactive stretch
      reflexes, but rather to an increased plantarflexor passive stiffness. In some of
      the patients, however, an increased TA activation that overcame the plantarflexor
      passive stiffness allowed for normal DFmax values. The functional consequences of
      the disturbed mechanisms of motor control observed in both the paretic and non
      paretic sides are discussed.

PMID- 11983500
TI  - The attentional demands of preferred and non-preferred gait patterns.
AB  - The purpose of this study was to determine the attentional demands of natural and
      imposed gait, as well as the attentional costs of transitions between the walking
      and running co-ordination patterns. Seven healthy young men and four healthy
      young women undertook an auditory probe reaction time task concurrently with self
      selected gait (Experiment 1) and imposed walking and running (Experiment 2) at
      different speeds on a motor-driven treadmill. In Experiment 1, where participants
      were free to choose their own movement pattern to match the speed of travel of
      the treadmill, normal gait control was shown to have a significant attentional
      cost, and hence not be automatic in the classical sense. However, this
      attentional cost did not differ between the two gait modes or at the transition
      point. In Experiment 2, where participants were required to maintain specific
      gait modes regardless of the treadmill speed, the maintenance of walking at
      speeds normally associated with running was found to have an attentional cost
      whereas this was not the case for running at normal walking speeds. Collectively
      the findings support a model of gait control in which the normal switching
      between gait modes is determined with minimal attention demand and in which it is
      possible to sustain non-preferred gait modes although, in the case of walking,
      only at a significant attentional/cognitive cost.

PMID- 11983501
TI  - Sudden release during a pulling task: the effect of release load on stance
      perturbation and recovery.
AB  - Ten subjects performed a horizontal pulling task with sudden release for three
      randomly allocated loads of 20, 40, and 60 N to examine the effect of sudden
      release load on centre of pressure (COP) motion and the response strategy with
      respect to load, and also to determine critical loads at which the response
      strategy must involve stepping to prevent a fall. Sudden release produces COP
      deflection directed posteriorly and laterally towards the anteroposterior
      midline. The magnitude of these deflections increase with release load (P<0.001),
      as does the time taken to re-establish normal stance following release (P<0.001).
      Interaction between lateral and anteroposterior shifts in the COP are seen
      following release, and establishing COP over a favoured limb may be an important
      factor in the response strategy. This may be so, because if the perturbation is
      large enough to provoke a protective step, then the COP will have to be located
      towards one limb before the step can take place. Linear regression of the
      anteroposterior limit of the COP indicates a wide range of critical loads that
      will result in a necessary preventive step backwards being taken (80-257 N, mean
      153 N), although these values are likely to be overestimated somewhat.

PMID- 11983502
TI  - Effects of caloric vestibular stimulation on head and trunk movements during
      walking.
AB  - The effects of vestibular stimulation on head and trunk movements were
      investigated during human walking (4.0 km/h). Vestibular stimulation was produced
      by irrigating an external auditory meatus with 4 degrees C ice water for 10 s.
      Using a 3-D motion analysis system, the linear (medial/lateral and vertical)
      translations and angular (yaw, pitch and roll) rotations were determined at the
      head, thorax, pelvis, knee, and foot. After caloric stimulation, waking
      trajectory deviated toward the stimulated side during dizziness. In addition, the
      amplitude of medial/lateral (M/L) linear translation and yaw rotation were
      significantly increased by caloric stimulation, especially at the head and
      thorax, whereas changes in vertical translation and pitch and roll rotations were
      not significant. The compensatory coordination (i.e., the yaw rotation to oppose
      the M/L linear translation) of the head was precisely maintained both before and
      after caloric stimulations, but it was decreased at the thorax and pelvis after
      stimulation. Our results suggested that vestibular sensory information, probably
      via the horizontal semicircular canals, contributes predominantly to the
      regulation of dynamic head and trunk movements in the M/L direction.

PMID- 11983503
TI  - Foot type classification: a critical review of current methods.
AB  - Investigation into the effects of foot structure on foot function, and the risks
      of injury, has been at the core of many studies, sometimes with conflicting
      results. Often different methods of foot type classification have been used,
      making comparison of the results and drawing sound conclusions impossible. This
      article aims to critically review current methods of foot type classification. It
      is concluded that if a classification method combines data on structure with
      information on foot function in dynamic loading situations, it should relate more
      closely to the functional behaviour of the foot during locomotion.

PMID- 11983504
TI  - In vitro monitoring sub-nanogram amounts analgin in human urine by its inhibitory
      of the luminol-periodate chemiluminescence reaction using reagent immobilization
      release technique.
AB  - A selective and sensitive as well as rapid chemiluminescence (CL) flow sensor for
      the determination of analgin is described. The analytical reagents involved in
      chemiluminescence reaction, luminol and periodate, were both immobilized on an
      anion-exchange column. The CL signals produced by the reaction between luminol
      and periodate, which were eluted from the column through water injection, were
      decreased in the presence of analgin. Analgin was sensed by measuring the
      decrement of CL intensity, and which was observed linear over the logarithm of
      analgin concentration range of 0.1 to 50.0 ng mL(-1), and the limit of detection
      was 0.04 ng mL(-1) (3o). At a flow rate of 2.0 mL min(-1), including sampling and
      washing, the detection could be performed in 0.5 min with a relative standard
      deviation of less than 3.0%. The proposed procedure was applied successfully in
      the monitoring of analgin in human urine samples without any pre-treatment
      process. It was found that the analgin concentration reached its maximum after
      being orally administrated for 4 h, and the analgin metabolism ratio in 10 h was
      9.28% in the body of volunteers. The flow sensor offered reagentless procedures
      and remarkable stability in determination of analgin, and could be easily reused
      over 80 h.

PMID- 11983505
TI  - RAR-RXR selectivity and biological activity of new retinoic acid analogues with
      heterocyclic or polycyclic aromatic systems.
AB  - The cell biological activity of novel retinoids and rexinoids is described. The
      stereochemistry of the new compounds was analyzed and ligand docking experiments
      revealed the structural basis of their RAR binding characteristics. The new
      ligands activate nuclear retinoic acid receptors (RAR, RXR) with distinct
      selectivity patterns, as determined in genetically engineered 'reporter' cells.
      The biological activity of the novel retinoids was assessed by differentiation of
      NB4 acute promyelocytic leukemia cells.

PMID- 11983506
TI  - Design and synthesis of a selective EP4-receptor agonist. Part 4: practical
      synthesis and biological evaluation of a novel highly selective EP4-receptor
      agonist.
AB  - A practical method of synthesizing a highly selective EP4-receptor agonist 1
      using Corey lactone 2 as a key intermediate was developed. Selective
      methanesulfonylation of the primary alcohol of the diol 8 under the newly devised
      conditions followed by the protection of the remaining secondary alcohol are key
      reactions in this new method. Further biological evaluation of 1a-b is also
      reported.

PMID- 11983507
TI  - Synthesis, and functional properties of a modified human insulin A-chain:
      implication in a 'mini-insulin' structure determination.
AB  - The design and total synthesis of a novel insulin A-chain mutant, analogue 3, is
      reported. In this compound, the cysteines implied in the two insulin inter-chain
      disulfide bridges are replaced by two serines (residues Ser(A7) and Ser(A20)) and
      the intra-A-chain disulfide bridge (residues Cys(A6) and Cys(A11)) is conserved.
      This A-chain analogue (3) has been tested in three in vitro cell culture assays,
      using insulin as a reference. The data clearly showed that analogue 3 mimics
      insulin effects on DNA synthesis, glucose uptake and glycogen synthesis without
      loss of potency as compared to insulin. To our knowledge, these are the first
      results showing that an isolated insulin chain displays functional properties
      similar to those of insulin. The implication of these new findings in insulin
      structure-function relationships and in a 'mini-insulin' structure determination
      is discussed.

PMID- 11983508
TI  - Synthesis, screening and quantitative structure-activity relationship (QSAR)
      studies of some glutamine analogues for possible anticancer activity.
AB  - We described the syntheses, biological activities and QSAR studies of 36 new 5-n
      substituted-2-(substituted benzenesulphonyl) glutamines 6-41 with different
      substitutions. These compounds were designed as structural analogues of most
      reactive amino acid, 'glutamine' (GLN), especially in the tumor cells. They
      present the new basic lateral chains at R(5) position as well as different
      substitutions at 2', 3', 4', and 5' positions on the benzene ring. The
      synthesized compounds have been tested for antitumor activity against Ehrlich
      ascites carcinoma (EAC) in Swiss albino mice using percentage inhibition of tumor
      weight as inhibitory parameter. In order to elucidate the structural requirements
      for antitumor activity, quantitative structure-activity relationship (QSAR)
      studies have been performed using extra thermodynamic model of Hansch. QSAR
      equations showed that the electronic parameter (sigma) on the aromatic ring
      system, steric parameter (Es) and to some extent Sterimol length of the
      substituent (L) on the aliphatic side chain correlate significantly with the
      antitumor activity. Resonance factor occupies the major electronic contribution
      on the aromatic ring system to the activity.

PMID- 11983509
TI  - Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline
      type alkaloids.
AB  - Hodgkinsine, a trimeric pyrrolidinoindoline type alkaloid, present as a major
      constituent of Psychotria spp. (Rubiaceae), has shown to produce dose-dependent,
      naloxone reversible, analgesic effect in thermal models of nociception and in the
      capsaicin-induced pain. SAR studies have been initiated by synthesizing the three
      diastereomeric dimers (chimonanthines) (11-13) which were evaluated in vitro and
      in vivo along with the synthetic intermediates. Strong binding affinities for mu
      opioid receptors were found for (-)- and (+)-chimonanthine monourethanes (9 and
      10), whereas (-)-, (+)- and (meso)-chimonanthine (11-13) and hodgkinsine
      displayed low affinity. In vivo data have shown that only (+)-chimonanthine (12)
      and calycosidine resemble the analgesic profile found for hodgkinsine.

PMID- 11983510
TI  - A new and efficient synthesis of substituted 6-[(2'-dialkylamino)ethyl]
      pyrimidine and 4-N,N-dialkyl-6-vinyl-cytosine derivatives and evaluation of their
      anti-rubella activity.
AB  - New 6-[(2'-dialkylamino)ethyl]-4(3H)-pyrimidinones were prepared by a multistep
      procedure starting from acetone dicarboxylic acid diethyl ester and urea
      derivatives. These compounds were used as starting materials to obtain 4-N,N
      dialkyl-6-vinyl-pyrimidine derivatives by an unprecedented tandem C-6 side chain
      Hofmann-like elimination/C-4 pyrimidinone substitution. Among the new derivatives
      obtained, various compounds show anti-Rubella activity. The inhibition of HIV-1
      Reverse Transcriptases (RT), from both wild type and modified viruses, is also
      reported.

PMID- 11983511
TI  - 1-Aza-sugars from D-glucose. Preparation of 1-deoxy-5-dehydroxymethyl
      nojirimycin, its analogues and evaluation of glycosidase inhibitory activity.
AB  - D-glucose derived pentodialdoses 11a-c on reduction followed by tosylation, azide
      displacement, hydrogenation and protection with -Cbz group gave N-Cbz protected
      compounds 14a-c, respectively, which on removal of 1,2-acetonide functionality
      and hydrogenation afforded corresponding 1-aza-sugars 3, 9 and 10 in good overall
      yields. The glycosidase inhibition activity of these 1-aza-sugars was tested with
      sweet almond as a rich source of different glycosidases.

PMID- 11983513
TI  - Enantioselective hydrolysis of naproxen ethyl ester catalyzed by monoclonal
      antibodies.
AB  - This report described that a hapten of racemic phosphonate 3 designed as the
      mimic of the transition state of hydrolysis of naproxen ethyl ester was
      successfully synthesized from easily available 2-acetyl-6-methoxy-naphthalene 5.
      Then BALB/C mice were immunized and one of the monoclonal catalytic antibodies,
      N116-27, which enantioselectively accelerated the hydrolysis of the R-(-)
      naproxen ethyl ester was given. The Michaelis-Menton parameter for the catalyzed
      reaction was K(M)=6.67 mM and k(cat)/k(uncat)=5.8 x 10(4). This enantioselective
      result was explained by the fact that the R-isomer of rac-hapten was more
      immunogenic than the S-isomer.

PMID- 11983512
TI  - Molecular structures and antiviral activities of naturally occurring and modified
      cassane furanoditerpenoids and friedelane triterpenoids from Caesalpinia minax.
AB  - Further investigation of the active components of the chloroform fraction of the
      seeds of Caesalpinia minax led to the isolation of a new cassane
      furanoditerpenoid, caesalmin H (1), together with two known furanoditerpenoid
      lactones, caesalmin B (2) and bonducellpin D (3). Reduction of the naturally
      abundant caesalmin D (9), E (10) and F (11) resulted in three new
      furanoditerpenoid derivatives 4-6. Phytochemical study of the stem of the same
      plant and subsequent reduction afforded two friedelane triterpenoids (7-8), which
      were identified by spectroscopic methods. Compounds 1-2 and 4-8 were corroborated
      by single crystal X-ray analysis. The factors governing the reduction of cassane
      furanoditerpenoids and friedelane triterpenoids were investigated by correlating
      the crystallographic results with density functional theory. The inhibitory
      activities of 2-8 on the Para3 virus were evaluated by cytopathogenic effects
      (CPE) reduction assay.

PMID- 11983514
TI  - Pyrazolo[3,4-b]quinoxalines. A new class of cyclin-dependent kinases inhibitors.
AB  - Protein kinases are involved in most physiological processes and in numerous
      diseases. Therefore, inhibitors of protein kinases have therefore a wide
      therapeutic potential. While screening for inhibitors of cyclin-dependent kinases
      (CDK's) and glycogen synthase kinase-3 (GSK-3), we identified pyrazolo[3,4
      b]quinoxalines as sub-micromolar inhibitors of CDK1/cyclin B. A preliminary
      structure-activity relationship study suggests that this family of compounds can
      be optimized to inhibit CDK's and GSK-3. Compounds were tested for their anti
      proliferative activity and the results show that several of them displayed a
      significant inhibitory effect on CDK1/cyclin B. The most active compound (1) was
      also tested against the brain kinases CDK5/p25 and GSK-3, and proved to be a good
      inhibitor of both of them. On the contrary, none of the compounds showed any
      activity in the CDC25 phosphatase assay. As an additional approach, affinity
      chromatography on immobilized pyrazolo[3,4-b]quinoxalines will be used to
      identify the intracellular targets of this family of compounds.

PMID- 11983515
TI  - Synthesis and biological evaluation of cyclopenta[c]thiophene related compounds
      as new antitumor agents.
AB  - A series of 22 cyclopenta[c]thiophene related compounds was obtained by the
      pharmacomodulation of 6-amino-5,6-dihydro-4H-cyclopenta[c]thiophen-4-ones 1a-g.
      All compounds were evaluated for potential anticancer activity in the NCI's in
      vitro human disease-oriented tumor cell line screening panel that consisted of 60
      human tumor cell lines arranged in nine subpanels, representing diverse
      histologies. Among these tested compounds, seven were found to be cytotoxic,
      especially against leukemia cell lines, allowing us to point out some structure
      activity relationships. These derivatives were further evaluated for potential in
      vivo anticancer activity in the hollow fiber assay developed at the NCI, which
      selected two compounds, 1f and 3a for standard xenograft testing.

PMID- 11983516
TI  - Synthesis and anti-tubercular evaluation of 4-quinolylhydrazones.
AB  - A series of 4-quinolylhydrazones were synthesized and tested against
      Mycobacterium tuberculosis H37Rv. Preparation of the title compounds was achieved
      by reaction of 4-quinolylhydrazine and aryl- or heteroaryl-carboxaldehyde. For
      the most of derivatives interesting antitubercular properties were showed; two
      compounds (3(2) and 3(25)), identified as the most active, were tested also
      against Mycobacterium avium.

PMID- 11983517
TI  - 4-Phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)
      acylpyrrolidines as prolyl oligopeptidase inhibitors.
AB  - New 4-phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)
      acylpyrrolidines were synthesized. Their inhibitory activity against prolyl
      oligopeptidase from pig brain was tested in vitro. In the series of 4
      phenylbutanoyl-2(S)-acylpyrrolidines, the cyclopentanecarbonyl and benzoyl
      derivatives were the best inhibitors having IC(50) values of 30 and 23 nM,
      respectively. This series of compounds shows that the P1 pyrrolidine ring, which
      is common in most POP inhibitors, can be replaced by either a cyclopentyl ring or
      a phenyl ring, causing only a slight decrease in the inhibitory activity. In the
      series of 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines the
      cyclopentanecarbonyl and benzoyl derivatives were not as active as in the series
      of 4-phenylbutanoyl-2(S)-acylpyrrolidines. The hydroxyacetyl derivative did
      however show high inhibitory activity. This compound is structurally similar to
      JTP-4819, which is one of the most potent prolyl oligopeptidase inhibitors. The
      acyl group in the two series of new compounds seems to bind to different sites of
      the enzyme, since the second series of new compounds did not show the same
      cyclopentanecarbonyl or benzoyl specificity as the first series.

PMID- 11983518
TI  - 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) and related
      derivatives: chemistry and biochemical effects on catecholamine biosynthesis.
AB  - 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo, 2) is a mammalian
      alkaloid that readily originates in the human organism, by Pictet-Spengler
      condensation of endogenously present tryptamine (Ta) and the non-natural hypnotic
      agent trichloroacetaldehyde (chloral, Clo). Due to its structural analogy to the
      neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 1), TaClo is
      discussed to possibly contribute to the pathogenesis of Parkinson's disease
      acting as an environmental toxin. Previous investigations on rats and neuronal
      cell cultures revealed 2 to be capable of inducing severe disturbances on the
      dopamine metabolism. In this paper, we report on the effects of 2 on the activity
      of tyrosine hydroxylase [L-tyrosine, tetrayhydropteridine/oxygen oxidoreductase
      (3-hydroxylating), EC 1.14,16.2; TH] in vitro using rat brain homogenates
      prepared from the TH-rich nucleus accumbens. TaClo (2) dose-dependently inhibited
      basal TH activity (IC(50)=3 microM), and after enzyme activation by pituitary
      adenylate cyclase-activating polypeptide (PACAP-27), it also reduced L-DOPA
      formation (IC(50)=15 microM). Moreover, two presumable TaClo metabolites, 2
      methyl-TaClo (N-Me-TaClo, 3) and 1-dichloromethylene-1,2,3,4-tetrahydro-beta
      carboline (1-CCl(2)-TH beta C, 4), which were synthesized in good yields, also
      proved to be potent inhibitors of TH, with the strongest effect on basal activity
      (similar to TaClo) being observed for 3 (IC(50)=3 microM). In contrast to TaClo,
      however, 3 and 4 showed biphasic effects after TH activation with PACAP-27,
      inducing a marked increase of enzyme activity in the nanomolar range (<0.1
      microM), while TH activity was nearly completely blocked at high concentrations
      (IC(100)=0.1mM). An X-ray diffraction investigation on the 3-dimensional
      structure of the 1-CCl(2)-TH beta C-derived trifluoroacetamide 7 revealed the
      voluminous and quite rigid dichloromethylene substituent to be only moderately
      twisted out of the beta-carboline ring 'plane', thus resulting in an increased
      ring strain of the partially hydrogenated pyrido moiety accompanied by a strong
      steric hindrance of Cl(1), Cl(2), C(13), and N(2), which pushes the N
      trifluoroacetyl group upwards to an even higher extent than for the TaClo-related
      trifluoroacetamide 8.

PMID- 11983519
TI  - Quantitative structure-activity relationships for a series of symmetrical
      bisquaternary anticancer compounds.
AB  - 56 biscationic dibromides with distinct polar heads [bis(4
      substituted)pyridinium, bis(4-aminoquinolinium), bisquinolinium, and
      bisisoquinolinium moieties] and several spacers between the two charged nitrogen
      atoms were synthesised. This oriented synthesis produced 45 inhibitors of choline
      kinase with antitumour activity against the HT-29 cell line. In an attempt to
      understand the antiproliferative activity, a quantitative structure-activity
      relationship was developed. The unknown sigma(R) and sigma(R)(+) descriptors for
      the diallylamino, pyrrolidino, piperidino and perhydroazepino groups and sigma(R)
      for the N-methylanilino moiety, were estimated by (13)C NMR spectroscopy in a
      simple, fast and reproducible manner. The electron characteristic of the
      substituent at position 4 of the heterocycle and the theoretical lipophilic
      character of the whole molecule were found to significantly affect the antitumour
      activity. 1,1'-[Ethylenebis(benzene-1,4-diylmethylene)]bis[4-(N
      methylanilino)pyridinium] dibromide is the most active compound of the series so
      far described and shows a reasonable agreement between predicted and observed
      antiproliferative data (predicted pIC(50)=6.50, experimental pIC(50)=6.46).

PMID- 11983520
TI  - Chemical studies on antioxidant mechanism of tea catechins: analysis of radical
      reaction products of catechin and epicatechin with 2,2-diphenyl-1-picrylhydrazyl.
AB  - Tea catechins, an important class of polyphenols, have been shown to have wide
      spectrum of antitumor activity believed to be due mainly to their antioxidative
      effect. In this study, the radical scavenging behavior of catechins on 2,2
      diphenyl-1-picrylhydrazyl (DPPH) was studied. Two reaction products of (+)
      catechin, and two reaction products of (-)-epicatechin were purified and
      identified. Their structures were determined on the basis of detailed high-field
      1-D and 2-D NMR spectral analysis. Structure elucidation of these products can
      provide insights into specific mechanisms of antioxidant reactions. A possible
      mechanism of the formation of reaction products is suggested.

PMID- 11983522
TI  - Conformationally constrained ethylenediamines: synthesis and receptor binding of
      6,8-diazabicyclo[3.2.2]nonanes.
AB  - The synthesis and receptor affinity of 6,8-diazabicyclo[3.2.2]nonanes
      representing conformationally constrained ethylenediamines are described. The
      Dieckmann analogous cyclization of the (piperazin-2-yl)propionate 9 provided the
      bicyclononane 10 only, when the first cyclization product was trapped with
      chlorotrimethylsilane. 10 was stereoselectively transformed into the bicyclic
      amines 19a,b and amides 22a,b, which were investigated in competition experiments
      with radioligands for their sigma(1)-, sigma(2)-, kappa-, and mu-receptor
      affinities. The (2R)-configured dimethylamine 19a showed promising sigma(1)
      receptor affinity (K(i)=23.8 nM) and selectivity, whereas the (2S)-configured
      (dichlorophenyl)acetamide 22b displayed a sigma-receptor binding profile
      (sigma(1): K(i)=184 nM; sigma(2): K(i)=263 nM) very similar to the binding
      profile of the atypical antipsychotic BMY-14802 (26).

PMID- 11983521
TI  - Supplementation of naringenin and its synthetic derivative alters antioxidant
      enzyme activities of erythrocyte and liver in high cholesterol-fed rats.
AB  - The antioxidative effects of naringenin (1) and its synthetic derivative,
      naringenin 7-O-cetyl ether (2), were tested. Male rats were fed a 1 g/100 g high
      cholesterol diet for 6 weeks with supplements of either 1 or 2 (0.073 mmol/100 g
      diet) to study the effects on the antioxidant enzyme activities in the
      erythrocyte and liver. The erythrocyte catalase (CAT) and superoxide dismutase
      (SOD) activities were significantly higher in the compounds 1 or 2 supplemented
      groups than in the control group, whereas the hepatic SOD and CAT activities were
      significantly lower in the compound 2 supplemented group. The compounds 1 and 2
      supplements to a high cholesterol diet lowered or tended to lower the plasma
      TBARS levels, that is, lipid peroxide products, while enhancing the plasma
      paraoxonase activity. These results indicate that the supplementation of 1 and 2
      was effective in improving the antioxidant capacity of the erythrocyte and liver,
      plus the synthetic functional compound 2 appeared to be as potent as 1 in
      enhancing the antioxidant defense system.

PMID- 11983523
TI  - 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute
      stereochemistry and enantiopharmacology at glutamate receptors.
AB  - In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands
      we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic
      acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed
      using a Crownpac CR(+) column affording (R)- and (S)-TDPA of high enantiomeric
      purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed
      that the early eluting enantiomer has R-configuration. Both enantiomers showed
      high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl)propionic acid (AMPA) receptors, determined using a
      [(3)H]AMPA binding assay and an electrophysiological model, respectively. The
      affinities and agonist activities obtained for (R)-TDPA (IC(50)=0.265 microM and
      EC(50)=6.6 microM, respectively) and (S)-TDPA (IC(50)=0.065 microM and EC(50)=20
      microM, respectively) revealed a remarkably low AMPA receptor stereoselectivity,
      (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist
      activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu
      uptake sites displacing [(3)H](R)-aspartic acid (IC(50 ) approximately 390
      microM). An enantiospecific and subtype-selective agonist activity was observed
      for (S)-TDPA at group I metabotropic Glu (mGlu) receptors (EC(50)=13 microM at
      mGlu(5) and EC(50)=95 microM at mGlu(1)).

PMID- 11983524
TI  - 3D-QSAR CoMFA and CoMSIA on protein tyrosine phosphatase 1B inhibitors.
AB  - 3D-QSAR and molecular modeling was performed on a series of
      benzofuran/benzothiophene biphenyls as protein tyrosine phosphatase 1B (PTP 1B)
      inhibitors with anti-hyperglycemic activity. Evaluation of 92 compounds served to
      establish the model, which was validated by evaluation of an external set of 26
      compounds. The lowest energy conformer of most active compound (compound 54)
      obtained from simulated annealing was used as a template structure for the
      alignment. The best predictions were obtained with the CoMFA model from RMS fit
      and A log P as additional descriptor (r(2)(cv)=0.615, r(2)=0.842), and with the
      CoMSIA combined steric, electrostatic, and lipophilic fields (r(2)(cv)=0.597,
      r(2)=0.910). The 3D-QSAR model was then superimposed to the PTP 1B active site,
      giving direct contour maps of the different fields. Further comparison of the
      contour maps from the 3D-QSAR showed high level of compatibility with the active
      site of PTP 1B enzyme.

PMID- 11983525
TI  - Hydroxyl radical as a strong electrophilic species.
AB  - In order to clarify an index which could be used as proof of the presence of
      hydroxyl radical, a new standard isomer distribution ratio of phenols formed from
      aromatic hydroxylation with [(4-bromophenyl)diazenyl](phenyl)methyl hydroperoxide
      4, which is a stable source of hydroxyl radical, under a new appropriate
      photolysis condition in the presence or absence of benzoquinones is reported. We
      also demonstrated the strong electrophilic properties of hydroxyl radical in
      reference to earlier results of electron density calculations.

PMID- 11983526
TI  - Synthesis of constrained phenylalanine derivatives via a [2+2+2] cycloaddition
      strategy.
AB  - A simple synthesis of dialkyne building blocks (6, 7, 8 and 9) embodying amino
      acid moiety is described. The dialkyne 6 participated in a [2+2+2] cycloaddition
      reaction with various monoalkynes in presence of Wilkinson's catalyst to give 5-
      and 5,6-disubstituted indan-based -amino acid derivatives. Cobalt catalyst [e.g.,
      CpCo(CO)2] has also been employed in the synthesis of various 2-indanyl glycine
      derivatives via co-trimerization reaction of the diyne building blocks 6 and 7
      with several monoalkynes.

PMID- 11983527
TI  - An efficient, convenient synthesis of novel medium-sized 13H
      dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione macrolides as anticipated
      antineoplastic agents.
AB  - A series of novel medium-sized 13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione
      macrolides (18-27, 30, 32) were synthesized in an ongoing effort to develop new
      antineoplastic agents. The synthon 2-(2-aminobenzoylamino)-benzoic acid (7), for
      preparation of the target compounds, was prepared via the reaction of isatoic
      anhydride 5 and anthranilic acid 6. Nine compounds (18-20, 24-27, 30, 32) were
      subjected to National Cancer Institute (NCI) in vitro disease-oriented human
      cells screening panel assay. Among the compounds tested, 6-benzyl-13H
      dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione (26, NSC 721327), bearing the benzyl
      group at position 6, showed cytotoxic activity and subpanel selectivity against
      leukemia (CCRF-CEM), colon (HCC-2998), CNS (SNB-75) and melanoma (UACC-257)
      panels at log(10) GI(50) (M), compound concentration that inhibits 50% of cell
      growth, ranging from -4.08 to -4.59.

PMID- 11983528
TI  - Synthesis and cytotoxicities of mannose conjugated S-nitroso-N
      acetylpenicillamine (SNAP).
AB  - A series of mannose conjugated S-nitroso-N-acetylpenicillamines (SNAPs) has been
      synthesized, and their cytotoxicities were assessed for DU 145 human prostate
      cancer cells and Hela R cancer cells.

PMID- 11983529
TI  - The difluoromethylenesulfonic acid group as a monoanionic phosphate surrogate for
      obtaining PTP1B inhibitors.
AB  - Three peptides, 7-9, bearing sulfono(difluoromethyl)phenylalanine (F(2)Smp, 2), a
      nonhydrolyzable, monoanionic phosphotyrosine mimetic, were prepared and evaluated
      as PTP1B inhibitors. The most effective inhibitor was the nonapeptide,
      ELEF(F(2)Smp)MDYE-NH(2), (9) which exhibited a K(i) of 360 nM. A comparison of
      F(2)Smp-bearing peptides 7 [DADE(F(2)Smp)LNH(2), K(i)=3.4 microM] and 8
      [EEDE(F(2)Smp)LNH(2), K(i)=0.74 microM] with their
      phosphono(difluoromethyl)phenylalanine (F(2)Pmp)-bearing analogues indicated that
      F(2)Smp is not as effective a pTyr mimetic as F(2)Pmp by 100- to 130-fold.
      Although F(2)Smp is not as effective as F(2)Pmp, a comparison of peptide 7 with
      analagous peptides bearing other monoanionic pTyr mimetics recently reported in
      the literature indicates that F(2)Smp is about 65-fold more effective than any
      other non-hydrolyzable, monanionic pTyr mimetic reported to date. To further
      assess the difluoromethylenesulfonic acid (DFMS) group as a monoanionic phosphate
      mimetic, a series of 24 nonpeptidyl biaryl compounds bearing the DFMS group were
      prepared using polymer-supported methodologies and screened for PTP1B inhibition.
      Several of these compounds were selected for further study and their IC(50)'s
      compared to their difluoromethylenephosphonic (DFMP) analogues. The differences
      in IC(50)'s between the DFMS and DFMP non-peptidyl compounds was not as great as
      with the F(2)Smp- and F(2)Pmp-bearing peptides. Possible reasons for this and its
      implication to the design of small molecule PTP1B inhibitors is discussed.

PMID- 11983530
TI  - Synthesis of conformationally restricted 2',3'-exo-methylene carbocyclic
      nucleosides built on a bicyclo[3.1.0]hexane template.
AB  - A series of 2',3'-exo-methylene carbocyclic nucleosides was synthesized as
      potential antiviral agents. These compounds were built on a bicyclo[3.1.0]hexane
      template that exhibits a rigid pseudoboat conformation and is capable of
      maintaining an identical conformation in solid state and in solution. The
      structures of the synthesized compounds were elucidated by NMR and X-ray
      crystallography. All the compounds were tested as anti-HIV and anti-HSV agents.
      The chemically synthesized 5'-triphosphate analogue of 7 was evaluated directly
      as a reverse transcriptase inhibitor.

PMID- 11983531
TI  - A simple method for the preparation of (5Z,8Z,11Z,14Z)-16-hydroxyeicosa-5,8,11,14
      tetraenoic acid enantiomers and the corresponding 14,15-dehydro analogues: role
      of the 16-hydroxy group for the lipoxygenase reaction.
AB  - (5Z,8Z,11Z,13E)-15-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) is not well
      oxygenated by arachidonate 15-lipoxygenases because of two structural reasons:
      (i) it contains a hydrophilic OH-group in close proximity to its methyl end and
      (ii) it lacks the bisallylic methylene at C(13). We synthesized racemic
      (5Z,8Z,11Z,14Z)-16-hydroxy-5,8,11,14-eicosatetraenoic acid (16-HETE) which still
      contains the bisallylic C(13), separated the enantiomers reaching an optical
      purity of >99% and tested them as substrates for 5- and 15-lipoxygenases. Our
      synthetic pathway, which is based on stereospecific hydrogenation of a
      polyacetylenic precursor, yielded substantial amounts (30%) of 14,15-dehydro-16
      HETE in addition to 16-HETE. When 16-HETE was tested as lipoxygenase substrate,
      we found that it is well oxygenated by the soybean 15-lipoxygenase and by the
      recombinant human 5-lipoxygenase. Analysis of the reaction products suggested an
      arachidonic acid-like alignment at the active site of the two enzymes. In
      contrast, the product pattern of 16-HETE methyl ester oxygenation by the soybean
      lipoxygenase (5-lipoxygenation) may be explained by an inverse head to tail
      substrate orientation.

PMID- 11983532
TI  - Novel piperidinyloxy oxazolidinone antibacterial agents. Diversification of the N
      Substituent.
AB  - Oxazolidinone antibacterial agents, where the morpholino group of linezolid was
      replaced with an N-substituted piperidinyloxy moiety, were synthesized and shown
      to be active against a variety of resistant and susceptible Gram-positive
      organisms. The functionality attached to the piperidine nitrogen was varied
      extensively to determine the SAR for this series. One of the most potent
      compounds, 11, showed in vivo efficacy upon subcutaneous administration in a
      Staphylococcus aureus Smith murine systemic infection.

PMID- 11983533
TI  - 2,2-Disubstituted analogues of the natural hormone 1 alpha,25-dihydroxyvitamin
      D(3): chemistry and biology.
AB  - Six new 2,2-disubstituted analogues of the natural hormone calcitriol have been
      prepared. Chemical novelty includes (1) the first example of an inverse-electron
      demand Diels-Alder cycloaddition using a pyrone diene and a difluorinated vinyl
      ether dienophile, leading to difluorinated analogues 7 and (2) a conceptually
      streamlined approach to dimethylated 19-nor analogues. Analogues 7a and are
      similar to calcitriol in terms of in vitro antiproliferative activity, but they
      are different from calcitriol in terms of transcriptional activity: difluorinated
      analogue 7a is 2-3 times more active transcriptionally than calcitriol, whereas
      dimethylated analogue is 7.5 times less active transcriptionally. Whereas the in
      vivo calcemic activity of difluorinated analogue 7a is similar to that of
      calcitriol, dimethylated analogue is considerably less calcemic than calcitriol.
      Dimethylated analogue strongly suppresses parathyroid hormone (PTH) secretion.

PMID- 11983534
TI  - Synthesis and chemical characterization of 2-methoxy-N(10)-substituted acridones
      needed to reverse vinblastine resistance in multidrug resistant (MDR) cancer
      cells.
AB  - In an attempt to find clinically useful modulators of multidrug resistance (MDR),
      a series of 19 N(10)-substituted-2-methoxyacridone analogues has been
      synthesized. 2-Methoxyacridone and its derivatives (1-19) were synthesized.
      Compound 1 was prepared by the Ullmann condensation of o-chlorobenzoic acid and p
      anisidine followed by cyclization using polyphosphoric acid. This compound
      undergoes N-alkylation in the presence of phase transfer catalyst (PTC). Stirring
      of 2-methoxy acridone with 1-bromo-3-chloropropane or 1-bromo-4-chlorobutane in a
      two-phase system consisting of organic phase (tetrahydrofuran) and 6N potassium
      hydroxide in the presence of tetrabutylammonium bromide leads to the formation of
      compounds 2 and 11 in good yield. N-(omega-Chloroalkyl) analogues were found to
      undergo iodide catalyzed nucleophilic substitution reaction with various
      secondary amines. Products were characterized by UV, IR, 1H and 13C NMR, mass
      spectral data and elemental analysis. The lipophilicity expressed in log(10) P
      and pK(a) of compounds have been determined. All compounds were examined for
      their ability to increase the uptake of vinblastine (VLB) in MDR KBCh(R)-8-5
      cells and the results showed that the compounds 7, 10, 12, and 15-19 at 100
      microM caused a 1.05- to 1.7-fold greater accumulation of vinblastine than did a
      similar concentration of the standard modulator, verapamil (VRP). However, the
      effects on VLB uptake were specific because these derivatives had little effect
      in the parental drug sensitive line KB-3-1. Steady state accumulation of VLB, a
      substrate for P-glycoprotein (P-gp) mediated efflux, was studied in the MDR cell
      line KBCh(R)-8-5 in the presence and absence of novel MDR modulators. Results of
      the efflux experiment showed that VRP and each of the modulators (1-19)
      significantly inhibited the efflux of VLB, suggesting that they may be
      competitors for P-gp. From among the compounds examined, 14 except 1, 2, 4, 8,
      and 11, exhibited greater efflux inhibiting activity than VRP. All the 19
      compounds effectively compete with [(3)H] azidopine for binding to P-gp, pointed
      out this transport membrane protein as their likely site of action. Cytotoxicity
      has been determined and the IC(50) values lie in the range 8.00-18.50 microM for
      propyl and 4-15 microM for butyl derivatives against KBCh(R)-8-5 cells suggesting
      that the antiproliferative activity increases as chain length increases from 3 to
      4 carbons at N(10)-position. Compounds at IC(10) were evaluated for their
      efficacy to modulate the cytotoxicity of VLB in KBCh(R)-8-5 cells and found that
      the modulators enhanced the cytotoxicity of VLB by 5- to 35-fold. Modulators 12,
      14-16, and 19 like VRP, were able to completely reverse the 24-fold resistance of
      KBCh(R)-8-5 cells to VLB. Examination of the relationship between lipophilicity
      and antagonism of MDR showed a reasonable correlation suggesting that
      hydrophobicity is one of the determinants of potency for anti-MDR activity of 2
      methoxyacridones.

PMID- 11983535
TI  - Synthesis and cytotoxic activity of N-(2-diethylamino)ethylcarboxamide and other
      derivatives of 10H-quindoline.
AB  - A series of mono- and dimeric N-methylquindoline carboxamides were prepared by
      Friedlander condensation between methyl 2-amino-3-formyl benzoate and 3-acetoxy-1
      acetylindoles, followed by exhaustive methylation with methyl iodide to give N
      methylquindoline esters. Direct amination of these, or hydrolysis to the acids
      and amine coupling via intermediate imidazolides gave the desired carboxamides.
      The compounds were evaluated in a panel of cell lines in culture. The monomeric
      compounds showed similar structure-activity relationships to the known indeno[1,2
      b]quinolines, with a 4-methyl group increasing potency several-fold. Bis
      analogues linked through the carboxamide were more cytotoxic than the
      corresponding monomers in the human leukemia lines, but N-N linked dimers were
      generally less potent, except for a tetracationic derivative. The most potent
      monomeric analogue showed moderate growth delay (ca. 5 days) against sub
      cutaneously implanted colon 38 tumors in mice.

PMID- 11983536
TI  - Design and syntheses of putative bioactive taxanes.
AB  - Reduction of 5 alpha-hydroxy-7 beta,9 alpha,10 beta-triacetoxy-4(20), 11(12)
      taxadien-13-one 1 with activated zinc in glacial acetic acid led to rearranged
      products, including compounds with double bonds at C3-C4, C10-C11 or with an
      epoxide at C11-C12. Molecular modeling studies suggested that addition of a side
      chain at C-20 or C-5 of the taxanes with a C3-C4 double bond might lead to
      bioactivity. Semi-syntheses and results of bioactivities are discussed.

PMID- 11983537
TI  - Synthesis and evaluation of taxol-folic acid conjugates as targeted
      antineoplastics.
AB  - A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate
      have been synthesized for evaluation as prodrugs which release Taxol via
      hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time
      for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in
      vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer,
      MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further
      screened for folate binding and competitive binding with free folic acid. One
      agent (54), further evaluated in animal studies was found to increase the
      lifespan in mice, but was less effective than Taxol itself.

PMID- 11983539
TI  - Assessment of synchrony relationships between the native left ventricle and the
      HeartMate left ventricular assist device.
AB  - BACKGROUND: It has been suggested that the cardiac cycle becomes synchronized
      with the LVAD. Synchronization between the left ventricle and the LVAD may be
      important for ventricular unloading and coronary flow. In this study, we assessed
      the synchrony between the cardiac and LVAD cycles. METHODS: We studied 24
      patients with HeartMate LVAD support. Native heart rate from an electrocardiogram
      and LVAD rate were measured at rest and peak exercise. Three patients underwent
      simultaneous invasive pressure measurement from the left ventricle and the aorta,
      and 3 patients underwent simultaneous recording of electrocardiogram and LVAD
      electrical signal. RESULTS: Resting heart rate was significantly higher than LVAD
      rate (96 +/- 17 vs 66 +/- 15 beats [b]/min, p < 0.0001), with no correlation
      between the 2 (r = 0.25). Peak heart rate was significantly higher than LVAD rate
      (142 +/- 16 vs 102 +/- 14 b/min, p < 0.0001), with no correlation observed (r =
      0.31). Electrical signal recording confirmed the absence of cardiac-LVAD
      synchrony. Pressure measurements revealed a cyclical intraventricular pressure
      variation, determined by the relationship between the cardiac and LVAD cycles.
      Intraventricular pressure was lowest when left ventricular systole occurred
      during pump filling and highest when left ventricular systole occurred during
      pump ejection. CONCLUSIONS: The cardiac and LVAD cycles are not in synchrony at
      rest or at peak exercise. However, a cyclical variation in left ventricular
      pressure exists, dependent upon the phasic relationship of the cardiac-LVAD
      cycles, which significantly effects ventricular loading. Better understanding of
      this relationship may be important in developing assist devices for optimal left
      ventricular unloading and improvement of myocardial recovery.

PMID- 11983540
TI  - Long-term follow-up of Thoratec ventricular assist device bridge-to-recovery
      patients successfully removed from support after recovery of ventricular
      function.
AB  - BACKGROUND: In certain forms of severe heart failure there is sufficient
      improvement in cardiac function during ventricular assist device (VAD) support to
      allow removal of the device. However, it is critical to know whether there is
      sustained recovery of the heart and long-term patient survival if VAD bridging to
      recovery is to be considered over the option of transplantation. METHODS: To
      determine long-term outcome of survivors of VAD bridge-to-recovery procedures, we
      retrospectively evaluated 22 patients with non-ischemic heart failure
      successfully weaned from the Thoratec left ventricular assist device (LVAD) or
      biventricular assist device (BVAD) after recovery of ventricular function at 14
      medical centers. All patients were in imminent risk of dying and were selected
      for VAD support using standard bridge-to-transplant requirements. There were 12
      females and 10 males with an average age of 32 (range, 12-49). The etiologies
      were 12 with myocarditis, 7 with cardiomyopathies (4 post-partum [PPCM], 1 viral
      [VCM], and 2 idiopathic [IDCM]), and 3 with a combination of myocarditis and
      cardiomyopathy. BVADs were used in 13 patients and isolated LVADs in 9 patients,
      for an average duration of 57 days (range, 11-190 days), before return of
      ventricular function and successful weaning from the device. Post-VAD survival
      was compared with 43 VAD bridge-to-transplant patients with the same etiologies
      who underwent cardiac transplantation instead of device weaning. RESULTS:
      Nineteen of the 22 patients are currently alive. Three patients required heart
      transplantation, 1 within 1 day, 2 at 12 and 13 months post-weaning, and 2 died
      at 2.5 and 6 months. The remaining 17 patients are alive with their native hearts
      after an average of 3.2 years (range, 1.2-10 years). The actuarial survival of
      native hearts (transplant-free survival) post-VAD support is 86% at 1 year and
      77% at 5 years, which was not significantly different (p = 0.94) from that of
      post-VAD transplanted patients, also at 86% and 77%, respectively. CONCLUSIONS:
      Long-term survival for bridge-to-recovery with VADs for acute cardiomyopathies
      and myocarditis is equivalent to that for cardiac transplantation. Recovery of
      the native heart, which can take weeks to months of VAD support, is the most
      desirable clinical outcome and should be actively sought, with transplantation
      used only after recovery of ventricular function has been ruled out.

PMID- 11983541
TI  - Cardiac transplant patients response to the (31)P MRS stress test.
AB  - BACKGROUND: Previous studies showed low resting phosphocreatine/adenosine
      triphosphate (PCr/ATP) ratios within this patient population compared with
      controls; however, these low PCr/ATP did not correlate with endomyocardial biopsy
      rejection. One possible explanation is the presence of cardiac allograft
      vasculopathy (CAV), which might be manifested as a transient ischemic event in
      the mildly stressed transplanted heart. If transient ischemia is invoked through
      the (31)P magnetic resonance spectroscopy (MRS) stress test, monitoring of such
      an event should be achievable and thus implicating possible ischemic involvement.
      METHODS: Heart transplant patients (n = 25) and normal controls (n = 11) were
      studied using the (31)P MRS stress test; 10 patients tested positive (> 2
      standard deviations [SDs] from control values). Patients also were monitored for
      heart rate and blood pressure with the handgrip exercise generating a small
      increase in the rate-pressure product. RESULTS: The percent change (%Delta) in
      the PCr/ATP ratio in the control group was 1.50% +/- 10.6; the transplant
      population showed an overall change of -6.7% +/- 18.5. The responders, those that
      were at or below the 2 SD line from control, had a -25.6 +/- 3.6% Delta PCr/ATP;
      whereas the non-responders reflect a 5.1 +/- 13.4%. The responders' response is
      quite striking when considering the threshold for an abnormal PCr/ATP %Delta in
      response to stress testing was -19.7%, which was the 2 SD mark below the mean
      value for the reference population. DISCUSSION: The (31)P MRS stress test showed
      that a possible transient ischemic event occurred in a subset of patients, thus
      implicating possible CAV in the cardiac transplant patient. Such an approach may
      provide an early diagnosis of this disease.

PMID- 11983542
TI  - Survival and incidence of acute rejection in heart transplant recipients
      undergoing successful withdrawal from steroid therapy.
AB  - BACKGROUND: Steroid-free immunosuppression is feasible in selected patients after
      heart transplantation. Survival and incidence of acute rejection are important
      parameters to evaluate when weighing risks and benefits of steroid withdrawal.
      METHODS: One hundred thirty-seven patients were retrospectively reviewed who
      underwent heart transplant at Emory University between January 1988 and April
      1994 and survived >1 year. Standard immunosuppression (cyclosporine, azathioprine
      and prednisone) without induction therapy was used. Weaning from steroids was
      attempted in all patients. Scheduled endomyocardial biopsy was used for long-term
      surveillance screening. RESULTS: Seventy-two patients (52.5%) underwent
      successful prednisone withdrawal (Group P0) at an average of 13 months after
      heart transplant, whereas 65 patients (47.5%) did not achieve steroid-free
      immunosuppression (Group P1). Group P0 had a mean of 1.3 treated rejection
      episodes (ISHLT Grade > or = 1b) during the first post-transplant year and Group
      P1 a mean of 2.3 (p <0.0001). In Group P0, 40 patients (55.6%) suffered a
      subsequent acute rejection with an ISHLT Grade > or = 1b, resulting in treatment.
      Of these, 15% were ISHLT Grade 1b, 47.5% Grade 2, 35% Grade 3a and 2.5% Grade 3b.
      The estimated risk of suffering from acute rejection of at least Grade 1b after
      achieving steroid-free immunosuppression was 50% at 21 months. Estimated survival
      at 5 years after heart transplant was 92.9% in Group P0 and 72.3% in Group P1 (p
      <0.01). Cox proportional hazard modeling revealed black recipient race as effect
      modifier of group status with decreased survival time in both groups. CONCLUSION:
      Steroid-free immunosuppression in white heart transplant recipients is associated
      with improved survival. A low acute rejection score during the first year
      predicts successful steroid withdrawal. Black recipient race appears to be
      negatively associated with survival and deserves further detailed study. Long
      term surveillance screening using endomyocardial biopsy is recommended.

PMID- 11983543
TI  - Sirolimus allows renal recovery in lung and heart transplant recipients with
      chronic renal impairment.
AB  - BACKGROUND: Until recently, there has been no practical alternative to the use of
      calcineurin inhibitors (CIs) as primary immunosuppressants in lung
      transplantation (LTx) and heart transplantation (HTx). Sirolimus (SRL) is a novel
      powerful immunosuppressant without renal toxicity, a common post-transplant
      problem associated with CI therapy. METHODS: SRL was used in 20 LTx and 5 HTx
      recipients >90 days post-transplant, where serious renal impairment was limiting
      CI dosing. Patients started on 2 to 5 mg/day orally at a median of 1,185 days
      post-transplant. Dosage adjustments were made according to trough levels,
      toxicity and perceived efficacy. With SRL initiation, 48% ceased CI therapy and
      the remainder decreased their dose substantively. RESULTS: After 30 days, 4 of 5
      dialyzed patients ceased dialysis and 15 of 20 patients with an elevated serum
      creatinine (Cr) (mean Cr 0.29 mmol/liter) improved their Cr. The direction of
      change in Cr at 30 days predicted longer term Cr. The starting Cr did not predict
      the 30-day or long-term value. There were two bouts of acute and one bout of
      chronic rejection. There were 35 infectious complications in 16 patients and 24
      episodes of potential SRL-related toxicity in 17 patients. These events generally
      responded to dose reduction or temporary cessation and were level-related.
      Fifteen recipients presently remain on the drug. None of the 7 deaths could be
      directly related to toxicity. CONCLUSION: SRL is a useful alternative
      immunosuppressant, allowing significant CI withdrawal in transplant recipients
      with renal impairment. Whether the resulting improvement in Cr can be maintained
      in the long term probably depends on the balance between the extent of acute and
      chronic renal damage.

PMID- 11983544
TI  - Anti-viral prophylaxis reduces the incidence of lymphoproliferative disease in
      lung transplant recipients.
AB  - BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a serious,
      often fatal complication after solid organ transplantation. Primary Epstein-Barr
      virus (EBV) infection is the major risk factor for PTLD after lung
      transplantation, with 30% to 50% of EBV-naive patients who seroconvert and are
      diagnosed with PTLD. METHOD: In this study, we analyzed the incidence of PTLD in
      lung and heart-lung transplant recipients before 1996 (historic group) and then
      compared the impact of long-term anti-viral prophylaxis on the development of
      PTLD in EBV-seronegative recipients from January 1996 to December 2000 (post-1996
      group). Routine induction therapy was not given after 1995. Patients not
      surviving 30 days, 25 of 341 (7.3%), were excluded. RESULTS: Historic group: PTLD
      developed in 7 of 167 (4.2%) patients, at a mean of 394 +/- 278 (95-885) days.
      The mortality was 87.5% at a mean follow-up of 186 +/- 207 (17-520) days after
      diagnosis. Post-1996 group: Eighteen of 149 (12.3%) patients were EBV
      seronegative at the time of transplantation, and of these 15 (83%) began
      receiving continuous anti-viral prophylaxis: acyclovir or valacyclovir or
      ganciclovir from January 1996. None of the EBV-seronegative recipients receiving
      continuous anti-viral prophylaxis were diagnosed with PTLD; however, 1 of 3 (33%)
      of the EBV-seronegative recipients who did not receive anti-viral prophylaxis
      were diagnosed with PTLD. In the EBV-seronegative recipients, no deaths had been
      caused by PTLD at a mean follow-up of 806 +/- 534 (39-1,084) days. In the post
      1996 group, PTLD developed in 1 of 131 (0.76%) EBV-seropositive recipients.
      CONCLUSION: Continuous, specific anti-viral prophylaxis in high-risk EBV
      seronegative recipients significantly reduces the incidence of PTLD after lung
      transplantation in the absence of induction therapy.

PMID- 11983545
TI  - A positive donor gram stain does not predict outcome following lung
      transplantation.
AB  - BACKGROUND: Many potential lung donors are excluded on the basis of a positive
      donor gram stain (DGS). We examined the association between a positive DGS and
      the probability of post-operative recipient pneumonia in the first 30 days.
      METHODS: Ninety lung transplants (80 with a non-septic pre-transplant diagnosis)
      from 60 consecutive donors were evaluated for post-operative pneumonia (defined
      as a compatible clinical syndrome with fever, leukocytosis, chest X-ray
      abnormalities or histologic evidence obtained by transbronchial biopsy). DGS,
      white blood cell quantity, CXR and PaO(2)/FIO(2) (P/F) ratio were compared with
      immediate and 24-hour P/F ratio, length of mechanical ventilation and incidence
      of pneumonia. All recipients received standard prophylactic anti-bacterial
      coverage. Patients not surviving 30 days (n = 3) were excluded from this study,
      but none had evidence of pneumonia either by bronchoalveolar lavage (BAL),
      transbronchial biopsy or autopsy. RESULTS: Fourteen (16%) of our 87 recipients
      developed pneumonia in the first 30 days after transplant. Of the 43 patients
      with a positive DGS, 5 (12%) developed pneumonia, compared to 9 of 44 (20%) with
      a negative DGS (p = 0.26). The mean post-operative P/F ratio (315 +/- 47 with a
      positive DGS, p = 0.3) and length of mechanical ventilation (2 days in each
      group) did not differ significantly between the negative and positive DGS groups.
      CONCLUSIONS: In the current era of lung transplantation, DGS does not predict the
      development of early post-operative pneumonia and does not affect oxygenation or
      duration of mechanical ventilation; therefore, its role should be diminished when
      judging donor lung suitability.

PMID- 11983546
TI  - Respiratory viruses and chronic rejection in lung transplant recipients.
AB  - BACKGROUND; Chronic rejection manifested as obliterative bronchiolitis (OB) and
      bronchiolitis obliterans syndrome (BOS) continue to be major causes of morbidity
      and mortality after lung transplantation. Community respiratory virus (CRV)
      infection, including respiratory syncytial virus, parainfluenza virus, and
      influenza virus, can infect and also cause morbidity in lung transplant
      recipients. Because CRV and OB/BOS affect the small airways, we sought to
      determine whether CRV infections predisposed patients to OB/BOS. METHODS: To
      determine whether CRV predisposed to OB/BOS, a proportional hazards regression
      analysis of time to OB/BOS was performed with CRV as a time-dependent covariate.
      To determine the influence of OB/BOS on the subsequent development of CRV
      infection, we reversed the outcome and time-dependent covariate. To illustrate
      the effect of CRV on OB/BOS and the effect of OB/BOS on CRV, landmark plots were
      generated at specific time points. Time to development of OB/BOS was then
      compared using the Kaplan-Meier method. RESULTS: In our institution, we
      documented 40 infections caused by CRV in 33 lung transplant recipients during an
      11-year period. Community respiratory virus infections occurred predominantly
      during seasonal community outbreaks, except for parainfluenza infections, which
      occurred throughout the year. The diagnosis of OB/BOS occurred throughout the
      year and was not associated with seasonal outbreaks of CRV. Community respiratory
      virus infection involving both upper and lower respiratory tracts did not
      predispose to OB or BOS (relative risk [RR], 1.1; 95% confidence interval [CI],
      0.52-2.3; p = 0.81). However, patients with documented CRV infection of the lower
      respiratory tract were predisposed to high-grade BOS development (RR, 2.3; 95%
      CI, 1.1-4.9; p = 0.04). In addition, a patient with pre-existing OB or BOS was
      predisposed to developing both upper and lower respiratory tract infection with
      CRV (RR, 4.2; 95% CI, 1.9-9.4; p < 0.001). CONCLUSIONS: Patients with CRV
      infection of the lower respiratory tract were predisposed to high-grade BOS
      development, and patients with OB and BOS were predisposed to CRV infections.

PMID- 11983547
TI  - Human allogeneic CD2+ lymphocytes activate airway-derived epithelial cells to
      produce interleukin-6 and interleukin-8. Possible role for the epithelium in
      chronic allograft rejection.
AB  - BACKGROUND: The adhesion of lymphocytes to the epithelium and the release of
      proinflammatory cytokines are important features observed during acute and
      chronic allograft rejection. Development of chronic rejection in lung
      transplantation patients is preceded by high levels of interleukin (IL)-6 and IL
      8 protein in the bronchoalveolar lavage. Therefore, we studied the expression of
      IL-6 and IL-8 in cocultures of epithelial cells and allogeneic lymphocytes.
      METHODS: IL-6 and IL-8 protein levels were determined in supernatants of the
      airway-derived epithelial cell line A549 and in primary epithelial cells obtained
      from lung-brushings after coculturing with autologous and allogeneic lymphocytes.
      Transcriptional mechanisms were detected by transient transfections. RESULTS:
      Coculture-supernatants of epithelial cells and allogeneic CD2+ lymphocytes show
      high levels of IL-6 and IL-8 protein due to transcriptional activation of the
      respective genes in epithelial cells. Highest productions were measured when the
      epithelial-cell:lymphocyte ratio was 1:10. Highly purified CD4+ and/or CD8+ cells
      were unable to induce the same response as observed with the total lymphocyte
      population. Depletion of CD4+ and/or CD8+ had no effect on the IL-6 and IL-8
      production induced by the total CD2+ lymphocyte-population. However, depletion of
      CD56+ cells diminished the lymphocyte-induced IL-6 and IL-8 production by > 75%.
      CONCLUSION: These data show that allogeneic CD2+ lymphocytes are able to activate
      lung-derived epithelial cells, resulting in the release of proinflammatory
      cytokines, which have a prominent role in chronic allograft rejection observed in
      lung-transplantation patients.

PMID- 11983548
TI  - Endogenous endothelium-derived nitric oxide inhibits myocardial caspase activity:
      implications for treatment of end-stage heart failure.
AB  - BACKGROUND: Apoptosis contributes to ventricular remodeling in heart failure
      (HF). Nitric oxide (NO) inhibits caspase 3, a key effector apoptotic enzyme. We
      hypothesized that reduced endogenous NO in HF disinhibits cardiac caspase 3 to
      promote apoptosis. METHODS: Caspase 3 activity was measured colorimetrically in
      myocardial cell lysates from endothelial NO synthase (eNOS)-deficient mice (eNOS 
      /-; n = 18), cardiomyopathic (CMP) hamsters (n = 8), and explanted failing human
      hearts (n = 10). We stimulated myocardial caspase 3 activity by adding upstream
      caspase 8 or 9. Cell lysates were incubated with 10(-4) mol/liter NO donor, S
      nitroso-N-acetyl penicillamine; NOS inhibitor, nitro-L-arginine-methyl ester (L
      NAME); or angiotensin-converting enzyme (ACE) inhibitor, enalaprilat. Hamsters
      underwent echocardiography so we could study the progression of ventricular
      dysfunction. RESULTS: Stimulated caspase 3 activity was lower in myocardium of
      eNOS +/+ compared with eNOS -/- mouse hearts (5.1 +/- 0.5 vs 7.6 +/- 1.0 pmol/10
      microg/min, p < 0.05). L-NAME increased enzyme activity only in eNOS +/+ mice,
      indicating that endogenous NO inhibits caspase 3. Stimulated caspase 3 activity
      was lower in control hamsters, 3.3 +/- 0.3 pmol/10 microg/min, compared with CMP
      hamsters, 9.6 +/- 0.7 and 6.9 +/- 0.4 pmol/10 microg/min at 4 and 9 months,
      respectively. This was associated with progressive ventricular dysfunction,
      thinning, and dilatation. L-NAME increased enzyme activity in normal but not in
      CMP hamsters. In failing human myocardium, L-NAME failed to alter caspase
      activity, indicating reduced NO availability. Enalaprilat inhibited caspase 3,
      which was reversed by L-NAME. S-nitroso-N-acetyl penicillamine reversed caspase 3
      activation in all groups. CONCLUSIONS: Nitric oxide reversibly inhibits
      myocardial caspase 3 independent of the apoptotic signaling pathway. Reduced NO
      in HF increases myocardial caspase 3 activity. Agents that promote NO synthesis,
      including ACE inhibitors, may prevent caspase activation in HF.

PMID- 11983549
TI  - Celsior solution provides superior post-ischemic right ventricular function as
      compared with UW solution in a porcine heart transplantation model.
AB  - BACKGROUND: Use of the new cardioprotective Celsior solution has been suggested
      for organ preservation in cardiac transplantation, but selective data for right
      ventricular function, of special interest in the clinical setting, have not been
      evaluated. METHODS: Celsior solution was compared with the clinical standard
      University of Wisconsin solution (UW) in a porcine allogenic heart
      transplantation model with accurate isovolumic measurement of right ventricular
      (RV) function. RESULTS: Maximum RV developed pressures were significantly
      different between Celsior and UW groups (51.1 +/- 9.6 mm Hg vs 42.2 +/- 15.4 mm
      Hg after 1 hour, respectively, and 55.6 +/- 7.8 mm Hg vs 45.1 +/- 16.2 mm Hg
      after 2 hours, respectively; p = 0.02, 2-way analysis of variance). CONCLUSIONS:
      Celsior significantly improves post-ischemic right ventricular function when
      compared with UW solution in an experimental heart transplantation model.

PMID- 11983550
TI  - Changes in the preserved heart that limit the length of preservation.
AB  - BACKGROUND: The variability in donor heart viability following preservation is
      well known and very dependent on the animal model used and the methods of
      preservation. Using hypothermia (2 to 4 degrees C) with the University of
      Wisconsin solution and microperfusion (3 microl/g/min) myocardial functional
      recovery after reperfusion is 50% to 60% after 18 hours of preservation. Many
      investigators have found the 18-hour preservation barrier for functional recovery
      of the heart with different experimental protocols. In previous studies, we have
      found in normothermic global ischemia that with necrosis there was a significant
      amount of apoptosis. It was therefore the purpose of this study to investigate
      the importance of apoptosis in heart preservation and determine if this cellular
      disruption plays a part in limiting heart viability during recovery from
      preservation. METHODS: Using a heterotopic heart transplant model, myocardial
      function (end-systolic elastance), high energy phosphate changes, metabolic
      substrate utilization, electron microscopy to determine degree of injury, and
      histologic changes that included apoptosis and lamin B(1) analyses were conducted
      on canine hearts preserved for 18 hours and reperfused for 6 hours. The changes
      were compared with a control group with no preservation. RESULTS: The 18-hour
      preserved heart regained approximately 50% to 60% of its original function, with
      significant decreases in adenosine triphosphate, no irreversible cellular changes
      (necrosis), and a 6% to 8% increase in apoptotic myocytes with a concomitant 8%
      decrease in lamin B(1). CONCLUSIONS: Preserved hearts can be maintained for
      approximately 12 hours with functional recovery near normal. However, approaching
      18 hours, there is an attenuated functional response which may be related to the
      to development of apoptosis.

PMID- 11983551
TI  - Co-expression of endothelin-1 and vascular endothelial growth factor mediates
      increased vascular permeability in lung grafts before reperfusion.
AB  - Endothelin-1 (ET-1) protein levels increase in lung transplant recipients,
      although the source of ET-1 remains uncertain. Evidence is accumulating that ET-1
      coregulates the expression of vascular endothelial growth/permeability factor
      (VEGF-A). By using real-time polymerase chain reaction and Western blotting, we
      describe upregulated ET-1 mRNA and VEGF-A protein levels as well as increased
      fluid content in donor lung-tissue biopsies before reperfusion. Hypoxia and ET-1
      co-upregulate VEGF-A overexpression, therefore temporary VEGF-A antagonism during
      graft preservation might be of benefit in lung transplantation.

PMID- 11983552
TI  - Long-term follow-up of patients treated with an implantable left ventricular
      assist device as an extended bridge to heart transplantation.
AB  - Four patients were given the TCI implantable left ventricular assist device as a
      bridge to heart transplantation. The median treatment time was 541 days (range
      462 to 873 days), with a total of 2,417 treatment days. The patients were
      followed with exercise tests and echocardiography 3 to 18 months after
      implantation. An invasive method was used for quantification of inflow valve
      incompetence.

PMID- 11983553
TI  - Do donor characteristics really matter? Short- and long-term impact of donor
      characteristics on recipient survival, 1995-1999.
AB  - We reviewed the impact of multiple donor characteristics on recipient mortality
      by univariate and multivariate analyses in a cohort of heart donors from 1995 to
      1999. A sub-cohort of donors was also selected who met "marginal" criteria, and
      the early and late survival of these patients was then compared. Surrogates of
      donor size (donor weight, donor body mass index [BMI], BMI mismatch >20%), under
      resuscitation (hematocrit, 24-hour fluid intake) and age >56 years were
      significantly associated with peri-operative mortality in the univariate
      analysis; in the multivariate analysis, only average donor heart rate at
      procurement (p =.001), donor hematocrit (p =.02) and donor weight (p =.05) were
      significantly associated. Few donor characteristics actually impact significantly
      on recipient outcome, and thus recipient characteristics may figure more
      prominently than those of the donor toward the risk of death after
      transplantation.

PMID- 11983554
TI  - Mass effect: a lethal complication of ventricular assist devices.

PMID- 11983555
TI  - Need for organized national efforts to improve donor-organ use.

PMID- 11983556
TI  - Bedside b-type natriuretic peptide and acute non-cellular cardiac allograft
      rejection.

PMID- 11983557
TI  - 1536-well assay plates: when do they make sense?

PMID- 11983558
TI  - Digital mice.

PMID- 11983559
TI  - CNS-targeted sexual dysfunction drug for men and women.

PMID- 11983560
TI  - Rapid immunotherapy for hayfever.

PMID- 11983564
TI  - The design of combinatorial libraries.

PMID- 11983563
TI  - Using machines in cells.

PMID- 11983565
TI  - Functional proteomics: separating the substance from the hype.

PMID- 11983566
TI  - Rethinking the formula.

PMID- 11983567
TI  - Pharmaceutical use of mouse models humanized for the xenobiotic receptor.
AB  - The regulation of hepatic cytochrome P450 (CYP) enzymes is implicated in both
      drug metabolism and drug-drug interactions. The CYP genes are induced by numerous
      xenobiotics, yet the inducibility shows clear species specificity. Recently, the
      rodent nuclear receptor PXR and its human homolog, SXR or hPXR, have been
      established as species-specific xeno-sensors that regulate CYP3A enzymes. By
      knocking-out the rodent gene and replacing it with the human receptor, a
      'humanized' mouse model has been established. Displaying a human drug-response
      profile, this mouse represents a unique tool to dissect the drug-induced
      xenobiotic response and should aid the development of safer drugs.

PMID- 11983568
TI  - Prioritizing the proteome: identifying pharmaceutically relevant targets.
AB  - Considerable attention is now being placed on prioritizing the proteome as the
      point of delivery for genomic information. Some of the challenges faced in
      prioritizing efforts from a pharmaceutical perspective, when presented with an
      incomplete proteome picture, are described. Examples of pharmaceutically relevant
      proteins are used to illustrate an informatics-based analysis of the proteome
      using knowledge of known drug targets. We show how results can be maximized by
      linking informatics approaches to experimental techniques and describe methods
      that can be used for prioritization within unprecedented protein families using,
      for example, single nucleotide polymorphism data and knowledge of disease
      pathways.

PMID- 11983569
TI  - Structure-based screening of low-affinity compounds.
AB  - Conventional bioassay-based screening remains a mainstream approach for lead
      discovery. However, its limitations have meant that other, more biophysical
      methods, such as X-ray crystallography and NMR, are now being developed as lead
      discovery tools. These methods are particularly effective at detecting the
      binding of low affinity, low molecular weight compounds and transforming them
      into novel potent leads using structure-guided chemistry. Here, we describe some
      of the technologies and approaches that are being developed in structure-based
      screening using X-ray crystallography, which promise to have a major impact on
      lead discovery.

PMID- 11983572
TI  - Drug delivery: Maximizing efficiency of nonviral gene delivery vehicles.

PMID- 11983573
TI  - New blood, new neurons em leader.

PMID- 11983574
TI  - Cognitive deficits, schizophrenia, and the anterior cingulate cortex.
AB  - Cognitive deficits are thought to be responsible for some of the symptoms and
      dysfunction in schizophrenia. Recent research on the anterior cingulate cortex
      supports this assumption. More detailed and definitive evidence for this
      association will require identification of specific neural networks whose
      abnormal structure, connections or activity create the cognitive deficits in
      question.

PMID- 11983575
TI  - Attempting to model dissociations of memory.
AB  - Kinder and Shanks report simulations aimed at describing a single-system model of
      the dissociation between declarative and non-declarative memory. This model
      attempts to capture both Artificial Grammar Learning (AGL) and recognition memory
      with a single underlying representation. However, the model fails to reflect an
      essential feature of recognition memory - that it occurs after a single exposure 
      and the simulations may instead describe a potentially interesting property of
      over-training non-declarative memory.

PMID- 11983576
TI  - Finding the timer.

PMID- 11983577
TI  - Sex is on the brain!

PMID- 11983579
TI  - Looking into autism.

PMID- 11983578
TI  - It's so noisy, you can't think straight.

PMID- 11983580
TI  - The heritability of language.

PMID- 11983582
TI  - The computational modeling of analogy-making.
AB  - Our ability to see a particular object or situation in one context as being 'the
      same as' another object or situation in another context is the essence of analogy
      making. It encompasses our ability to explain new concepts in terms of already
      familiar ones, to emphasize particular aspects of situations, to generalize, to
      characterize, to explain or describe new phenomena, to serve as a basis for how
      to act in unfamiliar surroundings, and to understand many types of humor. Within
      this framework, the importance of analogy-making in modeling cognition becomes
      clear.

PMID- 11983583
TI  - Paying attention to consciousness.
AB  - Despite being much studied by cognitive neuroscience, consciousness has resisted
      attempts to understand it. Recent neuroscientific papers on the problem have
      surprisingly neglected attention as a guide to consciousness. A new neural
      mechanism is proposed here, guided by a control approach to attention, which
      identifies the source of consciousness, especially that of the ownership of
      experience.

PMID- 11983584
TI  - The influence of visual motion on perceived position.
AB  - The ability of the visual system to localize objects is one of its most important
      functions and yet remains one of the least understood, especially when either the
      object or the surrounding scene is in motion. The specific process that assigns
      positions under these circumstances is unknown, but two major classes of
      mechanism have emerged: spatial mechanisms that directly influence the coded
      locations of objects, and temporal mechanisms that influence the speed of
      perception. Disentangling these mechanisms is one of the first steps towards
      understanding how the visual system assigns locations to objects when there are
      motion signals present in the scene.

PMID- 11983585
TI  - Imaging the medial temporal lobe: exploring new dimensions.
AB  - Cognitive scientists have used developments in functional imaging to explore the
      role of the medial temporal lobe (MTL) in memory formation. Lesion studies have
      suggested that separate MTL subregions make distinct contributions to memory.
      Functional imaging of these distinct contributions, however, remains a challenge,
      because the proximity of the MTL substructures tests the spatial resolution
      limits of current techniques. Recent findings using electrophysiological measures
      of neural activity highlight the importance of using information from other
      imaging modalities. Integrating the different modalities of neuroimaging with
      lesion studies, and, further, combining modalities within experiments, will
      provide new insights into the function of MTL subregions.

PMID- 11983587
TI  - Two sides of the same Universe.

PMID- 11983586
TI  - A considerable memory store.

PMID- 11983588
TI  - Updating the DALYs for diarrhoeal disease.
AB  - Estimates of global disease burden remain high on the international research and
      policy agenda as a forum for ranking health priorities. Within this, the quality
      of life or years lived with varying degrees of disability has been recognized as
      an important outcome that should be considered alongside estimates of mortality.
      Recent studies into the long-term consequences of diarrhoeal diseases on physical
      and mental development suggest that the disability adjusted life year
      calculations for these conditions could require updating.

PMID- 11983589
TI  - Invasion of skin by Schistosoma cercariae.
AB  - Schistosomiasis caused by Schistosoma spp. remains a major global health problem
      affecting >200 million people. The success of these parasites is a result of
      their adaptation to several different environments, including snail tissue, fresh
      water and mammalian blood; and their ability to switch between these environments
      rapidly. The initial step in infection of the human host involves penetration of
      the human skin by the aquatic form of Schistosoma, the cercaria. This aspect of
      host invasion is remarkable because no wounds or insect vectors are required and
      cercariae can penetrate through intact skin rapidly. The mechanisms of host
      finding and invasion represent fascinating and complex biological phenomenon,
      which are discussed here.

PMID- 11983590
TI  - Social sciences in malaria control.
AB  - The second annual meeting of the Partnership for Social Sciences in Malaria
      Control was held at the London School of Hygiene and Tropical Medicine, UK, from
      8 to 10 January 2002.

PMID- 11983591
TI  - Examining entamoeba.
AB  - A conference on Amebiasis and the Biology of Entamoeba histolytica was held in
      Agra, India, from 11 to14 February 2002.

PMID- 11983592
TI  - Toxoplasma gondii tachyzoite-bradyzoite interconversion.
AB  - During infection in the intermediate host, Toxoplasma gondii undergoes stage
      conversion between the rapidly dividing tachyzoite that is responsible for acute
      toxoplasmosis and the slowly replicating, encysted bradyzoite stage. This process
      of tachyzoite-bradyzoite interconversion is central to the pathogenesis and
      longevity of infection. Recent research has identified several stage-specific
      genes and proteins. However, despite recent advances in the understanding of
      Toxoplasma cell biology, more research is necessary to elucidate the complex
      events occurring during tachyzoite-bradyzoite interconversion. Here, a brief
      summary of this process is provided and a new method to characterize gene
      expression during interconversion is introduced.

PMID- 11983595
TI  - Your host or mine?

PMID- 11983598
TI  - Free insecticide for nets is cost effective.

PMID- 11983600
TI  - Helminthiasis: new medical significance.

PMID- 11983601
TI  - Mitochondrial genomes of parasitic flatworms.
AB  - Complete or near-complete mitochondrial genomes are now available for 11 species
      or strains of parasitic flatworms belonging to the Trematoda and the Cestoda. The
      organization of these genomes is not strikingly different from those of other
      eumetazoans, although one gene (atp8) commonly found in other phyla is absent
      from flatworms. The gene order in most flatworms has similarities to those seen
      in higher protostomes such as annelids. However, the gene order has been
      drastically altered in Schistosoma mansoni, which obscures this possible
      relationship. Among the sequenced taxa, base composition varies considerably,
      creating potential difficulties for phylogeny reconstruction. Long non-coding
      regions are present in all taxa, but these vary in length from only a few hundred
      to approximately 10000 nucleotides. Among Schistosoma spp., the long non-coding
      regions are rich in repeats and length variation among individuals is known. Data
      from mitochondrial genomes are valuable for studies on species identification,
      phylogenies and biogeography.

PMID- 11983602
TI  - Ehrlichia ruminantium infection (heartwater) in wild animals.
AB  - Several wild animal species have been implicated as hosts of Ehrlichia
      ruminantium (formerly Cowdria ruminantium), the rickettsial agent causing
      heartwater, a fatal disease of domestic ruminants in sub-Saharan Africa and
      eastern Caribbean. However, evidence for infection in most wild species is
      inconclusive because of inadequate diagnostic techniques. Infection has been
      proven only in 12 African ruminants, three non-African ruminants and two African
      rodents. A subclinical carrier state occurs in eight of the African ruminant
      species. Further studies on E. ruminantium infection in wild animal species are
      needed in order to determine the host range of this pathogen accurately. The host
      range of Ehrlichia ruminantium in wildlife is reviewed here and the role played
      by these species in the epidemiology and spread of heartwater is discussed.

PMID- 11983603
TI  - Trypanosoma evansi control and containment in Australasia.
AB  - Animal trypanosomosis caused by Trypanosoma evansi is endemic throughout
      Southeast Asia, where it is an important constraint on the productivity of
      smallholder livestock. In the past decade, T. evansi has emerged as a serious
      threat to the viability of smallholder livestock industries in the Philippines
      and causes severe disease outbreaks with high mortality. Trypanosoma evansi also
      poses a threat to livestock and native fauna in Australia and Papua New Guinea
      (PNG) where it is absent, but the risk of it spreading from Indonesia is high.
      Surveillance for T. evansi in PNG and Australia, and its control in the
      Philippines is restricted by the poor sensitivity and inadequate validation of
      existing diagnostic tests and lack of information on the determinants of
      infection.

PMID- 11983604
TI  - Combating malaria in Africa.
AB  - The spread of antimalarial drug resistance has major consequences for malaria
      control in tropical Africa. Here, the impact of chloroquine resistance on the
      burden of malaria is analyzed and its implications for the Roll Back Malaria
      initiative are examined. Malaria mortality has increased at least twofold during
      the past two decades. Combination therapy should be available for home treatment
      of young children. The potential toxicity of most antimalarials will require
      special surveillance programs. The main contribution to malaria control using
      methods to reduce the entomological inoculation rate is expected in areas with
      low or unstable transmission. Classic vector-control methods could potentially
      eliminate malaria in most urban areas and such programs deserve high priority.

PMID- 11983605
TI  - Ethical jurisdictions in biomedical research.

PMID- 11983632
TI  - Effects of antenatal stress and anxiety: Implications for development and
      psychiatry.

PMID- 11983633
TI  - Psychological consequences of traumatic injury.

PMID- 11983634
TI  - Seasonal affective disorder among general practice attenders.

PMID- 11983635
TI  - Efficacy and tolerability of venlafaxine compared with selective serotonin
      reuptake inhibitors and other antidepressants: a meta-analysis.
AB  - BACKGROUND: In individual studies and limited meta-analyses venlafaxine has been
      reported to be more effective than comparator antidepressants, particularly
      selective serotonin reuptake inhibitors (SSRIs). AIMS: To perform a systematic
      review of all such studies. METHOD: We conducted a systematic review of double
      blind, randomised trials comparing venlafaxine with alternative antidepressants
      in the treatment of depression. The primary outcome was the difference in final
      depression rating scale value, expressed as a standardised effect size. Secondary
      outcomes were response rate, remission rate and tolerability. RESULTS: A total of
      32 randomised trials were included. Venlafaxine was more effective than other
      antidepressants (standardised effect size was -0.14, 95% Cl -0.07 to -0.22). A
      similar significant advantage was found against SSRIs (20 studies) but not
      tricyclic antidepressants (7 studies). CONCLUSIONS: Venlafaxine has greater
      efficacy than SSRIs although there is uncertainty in comparison with other
      antidepressants. Further studies are required to determine the clinical
      importance of this finding.

PMID- 11983636
TI  - Genetic and host factors for dementia in Down's syndrome.
AB  - BACKGROUND: The high risk for dementia in adults with Down's syndrome has been
      attributed to triplication and overexpression of the gene for amyloid precursor
      protein (APP). But the wide variation in age at onset must be due to other risk
      factors. AIMS: To identify factors which influence age at onset of dementia in
      Down's syndrome. METHOD: Studies of factors which influence formation of beta
      amyloid (Abeta) were reviewed, including atypical karyotypes, susceptibility
      genotypes, gender and oestrogen deficiency, and individual differences in Abeta
      peptide levels. RESULTS: The apolipoprotein E epsilon4 allele, oestrogen
      deficiency and high levels of Abeta1-42 peptide are associated with earlier onset
      of dementia, while atypical karyotypes and the apolipoprotein E epsilon2 allele
      are associated with reduced mortality and reduced risk of dementia. CONCLUSIONS:
      Factors which influence Abeta levels, rather than overexpression of APP, may
      account for the differences in age at onset of dementia in Down's syndrome.

PMID- 11983637
TI  - Effects of exercise on depressive symptoms in older adults with poorly responsive
      depressive disorder: randomised controlled trial.
AB  - BACKGROUND: Depression is common in later life. AIMS: To determine whether
      exercise is effective as an adjunct to antidepressant therapy in reducing
      depressive symptoms in older people. METHOD: Patients were randomised to attend
      either exercise classes or health education talks for 10 weeks. Assessments were
      made "blind" at baseline, and at 10 and 34 weeks. The primary outcome was seen
      with the 17-item Hamilton Rating Scale for Depression (HRSD). Secondary outcomes
      were seen with the Geriatric Depression Scale, Clinical Global Impression and
      Patient Global Impression. RESULTS: At 10 weeks a significantly higher proportion
      of the exercise group (55% v. 33%) experienced a greater than 30% decline in
      depression according to HRSD (OR=2.51, P=0.05, 95% CI 1.00-6.38). CONCLUSIONS:
      Because exercise was associated with a modest improvement in depressive symptoms
      at 10 weeks, older people with poorly responsive depressive disorder should be
      encouraged to attend group exercise activities.

PMID- 11983638
TI  - Effectiveness of time-limited psychotherapy for minor psychiatric disorders:
      randomised controlled trial evaluating immediate v. long-term effects.
AB  - BACKGROUND: Psychotherapy research rarely has studied outcome in the longer term.
      AIMS: To evaluate the effectiveness of brief group dynamic psychotherapy (BGDP)
      intervention in patients with minor psychiatric disorders compared with the usual
      clinical management shortly after treatment termination and to investigate
      whether intervention would show a differential effect at 2-year follow-up.
      METHOD: Patients were allocated randomly to an experimental or control group. The
      General Health Questionnaire (GHQ) was used as a primary outcome measure.
      RESULTS: Based on improvement in the GHQ, at termination of treatment the BGDP
      group showed a significant improvement in 23 out of 42 (54.8%) compared with 11
      out of 41 (26.8%) in the clinical management group. The difference in the total
      improvement rate is 28% (95% C18-48) (chi(2)=6.7; d.f.=1; P=0.009). In contrast,
      no differential follow-up effects were found between the BGDP and clinical
      management groups. CONCLUSIONS: Psychotherapy appears to have beneficial effects
      at termination of treatment but the changes attained were not stable.

PMID- 11983639
TI  - Sexual orientation and mental health: results from a community survey of young
      and middle-aged adults.
AB  - BACKGROUND: Community surveys have reported a higher rate of mental health
      problems in combined groups of homosexual and bisexual participants, but have not
      separated these two groups. AIMS: To assess separately the mental health of
      homosexual and bisexual groups compared with heterosexuals. METHOD: A community
      survey of 4824 adults was carried out in Canberra, Australia. Measures covered
      anxiety, depression, suicidality, alcohol misuse, positive and negative affect
      and a range of risk factors for poorer mental health. RESULTS: The bisexual group
      was highest on measures of anxiety, depression and negative affect, with the
      homosexual group falling between the other two groups. Both the bisexual and
      homosexual groups were high on suicidality. Bisexuals also had more current
      adverse life events, greater childhood adversity, less positive support from
      family, more negative support from friends and a higher frequency of financial
      problems. Homosexuals reported greater childhood adversity and less positive
      support from family. CONCLUSIONS: The bisexual group had the worst mental health,
      although homosexual participants also tended to report more distress.

PMID- 11983640
TI  - Mental health and the built environment: cross-sectional survey of individual and
      contextual risk factors for depression.
AB  - BACKGROUND: Little is known about the effects of the physical environment on
      individual health. AIMS: The present study tested the hypothesis that the
      prevalence of depression is associated with independently rated measures of the
      built environment, after adjusting for individuals' socio-economic status and the
      internal characteristics of their dwellings. METHOD: Cross-sectional survey of
      1887 individuals aged 16 years and over in two electoral wards in north London.
      Depression was ascertained using the Center for Epidemiologic Studies Depression
      scale (CES-D). The built environment was rated independently, using a validated
      measure. RESULTS: After adjusting for socio-economic status, floor of residence
      and structural housing problems, statistically significant associations were
      found between the prevalence of depression and living in housing areas
      characterised by properties with predominantly deck access (odds ratio=1.28, 95%
      CI 1.03-1.58; P=0.02) and of recent (post-1969) construction (odds ratio=1.43,
      95% CI 1.06-1.91; P=0.02). CONCLUSIONS: The prevalence of depression was
      associated with independently rated features of the built environment,
      independent of individuals' socio-economic status and internal characteristics of
      dwellings.

PMID- 11983641
TI  - Chronic, treatment-resistant depression and right fronto-striatal atrophy.
AB  - BACKGROUND: Treatment-resistant depression (TRD) is relatively common but its
      neurobiological basis is poorly understood. Fronto-striatal structural brain
      changes have been reported in patients with depression but their association with
      treatment resistance and chronicity has not been established. METHOD: Magnetic
      resonance images of 20 patients with TRD were compared with images of 20
      recovered patients and 20 healthy controls. Images were compared using a voxel
      based analysis (VBA) method; the results were validated by conventional
      volumetric analysis. The clinical associations of magnetic resonance imaging
      (MRI) changes with illness duration and severity were examined by VBA. RESULTS:
      Only the TRD group exhibited right fronto-striatal atrophy, and subtle MRI
      changes in the left hippocampus on VBA. Atrophy was confirmed on volumetric
      analysis, the degree correlating with the cumulative number of electroconvulsive
      therapy (ECT) treatments received, suggesting an acquired deficit. CONCLUSIONS:
      This is the first study to demonstrate fronto-striatal atrophy in patients with
      depression with poor outcome; the atrophy is more marked in those with more
      severe illness.

PMID- 11983642
TI  - Psychiatry of whiplash neck injury.
AB  - BACKGROUND: The psychiatric outcome of whiplash neck injury is controversial.
      AIMS: To describe outcomes and predictors as compared with other types of road
      accident injury. METHOD: Consecutive emergency department attenders (n=1148;
      whiplash 278) assessed by self-report at baseline, 3 months, 1 year and 3 years.
      RESULTS: Moderate to severe pain was reported by 27% of whiplash sufferers at 1
      year and by 30% at 3 years. Psychiatric consequences were common and persistent.
      Whiplash victims and those with bony injury were more likely to seek
      compensation. Accident and early post-accident psychosocial variables predicted
      the pain at 1 year. Claiming compensation at 3 months predicted the pain at 1
      year for those with whiplash or bony injury. CONCLUSIONS: There is no special
      psychiatry of whiplash neck injury. Psychological variables and consequences are
      important following whiplash in a similar manner to other types of injury.

PMID- 11983643
TI  - Use of health care services in seasonal affective disorder.
AB  - BACKGROUND: Little is known about the presentation and management of seasonal
      affective disorder (SAD) in primary care. AIMS: To determine the use of health
      care services by people suffering from SAD. METHOD: Following a screening of
      patients consulting in primary care, 123 were identified as suffering from SAD.
      Each was age- and gender-matched with two primary care consulters with minimal
      seasonal morbidity, yielding 246 non-seasonal controls. From primary care
      records, health care usage over a 5-year period was established. RESULTS:
      Patients with SAD consulted in primary care significantly more often than
      controls and presented with a wider variety of symptoms. They received more
      prescriptions, underwent more investigations and had more referrals to secondary
      care. CONCLUSIONS: Patients with SAD are heavy users of health care services.
      This may reflect the condition itself, its comorbidity or factors related to the
      personality or help-seeking behaviour of sufferers.

PMID- 11983644
TI  - Genetics, molecular biology, neuropathology and phenotype of frontal lobe
      dementia: a case history.
AB  - BACKGROUND: Mutations in tau have been found in a group of related disorders
      including the frontal lobe dementias. AIMS: To describe the clinical features and
      molecular pathology changes in a single case of a patient with frontal lobe
      dementia. METHOD: A case report was compiled from neuropathological reports and
      genomic and gene expression analyses. RESULTS: A case with a splice-site mutation
      resulting in a typical frontotemporal clinical and neuropathological phenotype
      was found. Gene expression analysis suggests differential expression of isoforms
      of tau in regions in the brain. CONCLUSIONS; Frontotemporal dementia can result
      from gene mutations that alter splicing and expression of tau.

PMID- 11983645
TI  - The Work and Social Adjustment Scale: a simple measure of impairment in
      functioning.
AB  - BACKGROUND: Patients' perspectives concerning impaired functioning provide
      important information. AIMS; To evaluate the reliability and validity of the Work
      and Social Adjustment Scale (WSAS). METHOD: Data from two studies were analysed.
      Reliability analyses included internal scale consistency, test-retest and
      parallel forms. Convergent and criterion validities were examined with respect to
      disorder severity. RESULTS: Cronbach's alpha measure of internal scale
      consistency ranged from 0.70 to 0.94. Test-retest correlation was 0.73.
      Interactive voice response administrations of the WSAS gave correlations of 0.81
      and 0.86 with clinician interviews. Correlations of WSAS with severity of
      depression and obsessive-compulsive disorder symptoms were 0.76 and 0.61,
      respectively. The scores were sensitive to patient differences in disorder
      severity and treatment-related change. CONCLUSIONS: The WSAS is a simple,
      reliable and valid measure of impaired functioning. It is a sensitive and useful
      outcome measure offering the potential for readily interpretable comparisons
      across studies and disorders.

PMID- 11983646
TI  - Atypical antipsychotics, cortical D(2) receptors and sensitivity to endogenous
      dopamine.

PMID- 11983647
TI  - Asphyxia at birth and schizophrenia.

PMID- 11983648
TI  - Prolonged QT interval with rivastigmine.

PMID- 11983649
TI  - From mental hospitals to community care.

PMID- 11983650
TI  - Diagnosis of vascular dementia.

PMID- 11983651
TI  - Confusion.

PMID- 11983653
TI  - Focus on psychiatry in New Zealand.

PMID- 11983655
TI  - Science, pseudoscience and Sellick.

PMID- 11983656
TI  - Modelling the difficult airway -- how real is faking it?

PMID- 11983657
TI  - Nausea and vomiting after laparoscopic surgery are not associated with an
      increased peripheral release of serotonin.
AB  - PURPOSE: To determine whether patients suffering postoperative nausea and
      vomiting (PONV) present a different serotonin release pattern from those who do
      not present this complication. METHODS: Forty-eight consecutive women undergoing
      outpatient laparoscopic tubal ligation were enrolled in this prospective,
      cumulative case-control study. The study compared serotonin activity in 15
      patients totally free of emetic symptoms (asymptomatic group) and, among patients
      with PONV (n = 33), those 15 who presented the most severe symptoms (PONV group).
      Patients were anesthetized with a regimen including sufentanil (0.1-0.3 microg x
      kg(-1)) plus thiopental (3-5 mg x kg(-1)) for induction and isoflurane (0.6-1%)
      in nitrous oxide (60%) for maintenance. Peripheral serotonin activity was
      assessed by measurement with high-performance liquid chromatography of
      serotonin's principal urinary metabolite: 5-hydroxyindoacetic acid (5-HIAA)
      corrected for urinary creatinine. RESULTS: The preoperative and postoperative
      urinary 5-HIAA:creatinine ratios were 6.9 ng x microg(-1) (confidence interval;
      CI 95%, 2.7-11.0) and 5.9 ng x microg(-1) (CI 95%, 2.4-9.4) respectively in the
      asymptomatic group (P = 0.69), and were 5.1 ng x microg(-1) (CI 95%, 2.5-7.7) and
      5.6 ng x micro(-1) (CI 95%, 3.4-7.7) respectively in the PONV group (P = 0.75).
      There was also no difference between groups in the variation of 5-HIAA:creatinine
      ratios from the preoperative to the postoperative period (P = 0.21). CONCLUSION:
      PONV after laparoscopic tubal ligation are not associated with an increased
      urinary excretion of serotonin metabolites. Patients with severe PONV present a
      peripheral serotonin release comparable to asymptomatic patients.

PMID- 11983658
TI  - The bispectral index response to tracheal intubation is similar in normotensive
      and hypertensive patients.
AB  - PURPOSE: To compare the hemodynamic and bispectral index (BIS) responses to
      tracheal intubation in normotensive and hypertensive patients. METHOD: Three
      minutes after induction of anesthesia with thiamylal and fentanyl, tracheal
      intubation was performed in 24 normotensive and 22 hypertensive patients. Heart
      rate (HR), mean arterial pressure (MAP), and BIS were measured every minute.
      RESULTS: Tracheal intubation increased HR, MAP, and BIS in both normotensive and
      hypertensive patients. The increase in MAP was significantly greater in
      hypertensive patients than in normotensive patients, but there were no
      differences in HR or BIS in the two groups of patients. CONCLUSION: Patients with
      and without hypertension exhibit the same arousal response (as measured by BIS)
      to tracheal intubation despite the enhanced vasopressor response in hypertensive
      patients.

PMID- 11983659
TI  - Low-dose ketorolac improves analgesia and reduces morphine requirements following
      posterior spinal fusion in adolescents.
AB  - PURPOSE: To determine if low-dose ketorolac would improve analgesia while
      minimizing unwanted side effects in adolescents following posterior spinal fusion
      (PSF). METHODS: A prospective randomized double-blind placebo-controlled trial
      assessed the analgesic effects of low-dose ketorolac following PSF. Thirty-five
      adolescents aged 11-17 yr were randomly assigned to receive placebo or 0.5 mg x
      kg(-1) ketorolac (maximum of 15 mg) six hourly postoperatively for 36 hr in
      conjunction with standard morphine patient controlled analgesia (PCA). Pain and
      sedation were assessed twice daily for the first three postoperative days (POD).
      The incidence of side effects related to both non-steroidal anti-inflammatory
      agents and opioids were recorded. RESULTS: Adolescents in the ketorolac group
      received an average dose of 0.2 mg x kg(-1) (average exposure 1.2 mg x kg(-1)),
      had lower pain scores on POD one and two (P < 0.05) and consumed less morphine in
      the postanesthesia care unit and on POD two. There was no difference in the
      incidence of pruritus, nausea, vomiting or constipation, but patients in the
      ketorolac group tolerated activity better on POD one (P < 0.05). There were no
      differences between groups with regard to postoperative blood loss or transfusion
      requirements. Fourteen patients were followed for two years and the incidence of
      curve progression, hardware failure or back pain at final follow-up was not
      different. CONCLUSION: Low-dose ketorolac in conjunction with morphine PCA
      improved the quality of analgesia and reduced morphine requirements following PSF
      compared to placebo without increasing the incidence of non-steroidal anti
      inflammatory side effects.

PMID- 11983660
TI  - The anesthetic management of a patient with Emery-Dreifuss muscular dystrophy for
      orthopedic surgery.
AB  - PURPOSE: To report a patient with Emery-Dreifuss muscular dystrophy (EDMD) coming
      for an orthopedic procedure, with potential problems of sudden cardiac death,
      difficult airway, and neuromuscular disorders who was managed successfully by
      permanent pacemaker insertion, total iv anesthesia (TIVA), laryngeal mask
      insertion (LMA) insertion and continuous epidural blockade. CLINICAL FEATURES: A
      22-yr-old man with known EDMD presented for triple arthrodesis of his right foot
      and fractional lengthening of his hamstrings bilaterally. Anesthesia was induced
      with a TIVA technique, and maintained throughout the operative period. A
      suspected difficult airway was managed by the use of a LMA, and analgesia for the
      peri-, and postoperative period provided by a continuous epidural infusion. The
      patient's perioperative course was uneventful. CONCLUSION: EDMD is a rare
      disorder. However, anesthesia is often required for orthopedic procedures. This
      case report illustrates the many potential difficulties that may be encountered.
      Regional anesthesia combined with light general anesthesia offers a method of
      avoiding many of these difficulties.

PMID- 11983661
TI  - Sevoflurane reduces endothelium-dependent vasorelaxation: role of superoxide
      anion and endothelin.
AB  - PURPOSE: There are several reports suggesting that volatile anesthetics alter
      vascular endothelial function. We analyzed the effect of sevoflurane, a
      fluorinated volatile anesthetic, on nitric oxide (NO)-dependent relaxation,
      evaluating the role of the endothelium-derived vasoconstrictor endothelin-1 (ET
      1). METHODS: The experiments were performed in rat isolated aortic segments
      aerated in the absence and in the presence of sevoflurane (2%). RESULTS:
      Acetylcholine-induced relaxation was reduced in aortic segments aerated with
      sevoflurane. Sevoflurane failed to modify relaxation in response to an exogenous
      NO donor, sodium nitroprusside. Superoxide dismutase, a scavenger of superoxide
      anion, partially restored the impaired vasorelaxation induced by sevoflurane, an
      effect that was associated with the release of superoxide anion. The presence of
      BQ-123, an antagonist of endothelin ETA-type receptors, normalized the
      vasorelaxing response to acetylcholine in the presence of sevoflurane. In
      addition, BQ-123 also reduced the ability of the sevoflurane-incubated vascular
      wall to release superoxide anion. CONCLUSIONS: Our results suggest that
      sevoflurane impairs the endothelium-dependent vasorelaxation but that the
      endothelium-independent response remains intact. ET-1 and superoxide anion are
      involved in the endothelial dysfunction induced by sevoflurane. Further studies
      are needed to associate the endothelial dysfunction related to sevoflurane shown
      herein and its reported preconditioning properties on the myocardium.

PMID- 11983662
TI  - Therapeutic concentrations of propofol protects mouse macrophages from nitric
      oxide-induced cell death and apoptosis.
AB  - PURPOSE: To evaluate the potential effect of a clinically relevant concentration
      of propofol (PPF) on cell viability and nitric oxide-induced macrophage
      apoptosis. METHODS: Mouse macrophages (cell line Raw 264.7) were cultured and
      incubated with a nitric oxide donor sodium nitroprusside (SNP), PPF, and a
      combination of PPF and SNP for one, six and 24 hr. Cell viability was determined
      by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. Apoptotic cells were determined by analyzing the percentages of sub-G1
      phase in macrophages. The amounts of nitric oxide were assayed. RESULTS: The
      amounts of nitric oxide in macrophages were increased with time when incubated
      with SNP (P < 0.05). Simultaneously, SNP caused cell death of macrophages in a
      concentration-and time-dependent manner (P < 0.05). PPF per se did not alter the
      amount of basal and SNP-provided nitric oxide in macrophages. A therapeutic
      concentration of PPF (30 microM) exhibited no cytotoxicity. After incubation with
      SNP for one and six hours, PPF could completely or partially block nitric oxide
      induced cell death, respectively (P < 0.05). Administration of SNP to macrophages
      resulted in a time-dependent pattern of increase of apoptotic cells (P < 0.05).
      Similar to the results of the cell viability analyses, PPF was able to protect
      macrophages from nitric oxide-induced apoptosis in one and six hour-treated
      groups (P < 0.05) but not in the 24 hr treated group. CONCLUSION: PPF, at a
      therapeutic concentration, can protect mouse macrophages in vitro from nitric
      oxide-induced cell apoptosis as well as cell death.

PMID- 11983663
TI  - Incisional self-administration of bupivacaine or ropivacaine provides effective
      analgesia after inguinal hernia repair.
AB  - PURPOSE: To evaluate the safety and applicability of two local anesthetic (LA)
      solutions self-administered for pain treatment after inguinal hernia repair (IHR)
      by balloon-pumps via catheters placed in the surgical wound. Effectiveness of
      analgesia was also compared. METHODS: Two groups of patients for IHR were
      included in the randomized, double-blind study. An epidural catheter was placed
      in the surgical wound, tunneled subcutaneously and connected to a balloon-pump
      containing either 0.25% bupivacaine (B) or 0.25% ropivacaine (R).
      Postoperatively, the patient self-administered the LA into the wound.
      Administration could be repeated after 20 min. If moderate to severe pain still
      persisted, rescue medication (piritramid) was given intravenously. The variables
      recorded in both groups were: visual analogue scale (VAS), pain scores at rest
      and with movement, number of applications, wound healing, patients' satisfaction.
      RESULTS: During the first 24 hr, median number of LA applications in 26 B
      patients was 4 (range 1-6) and in 25 R patients 3 (range 1-5). Both groups showed
      low VAS pain scores: less than 2 at rest, less than 4 with movement. Eighty
      percent of patients of each group would choose this type of analgesia again. Two
      patients from B Group and three from R Group needed rescue medication. No wound
      infection was observed. There were no statistically significant differences
      between the groups. CONCLUSION: Self-administration of the LA solution via a
      catheter in the surgical wound is an effective method of pain relief after IHR
      with little side-effects.

PMID- 11983664
TI  - Continuous retrobulbar anesthesia for scleral buckling surgery using an ultra
      fine spinal anesthesia catheter.
AB  - PURPOSE: To evaluate a novel retrobulbar catheter technique for intraoperative
      and postoperative analgesia in patients undergoing scleral buckling procedures.
      METHODS: This prospective noncomparative clinical interventional case-series
      study included 43 consecutive patients undergoing scleral buckling procedures as
      treatment of rhegmatogenous retinal detachments. Using a commercially available
      retrobulbar needle with a diameter of 0.80 mm and a length of 38 mm, 7 mL of
      local anesthetic were injected into the retrobulbar space. Through the same
      needle, a 28-gauge commercially available flexible spinal anesthesia catheter was
      introduced into the retrobulbar space, the needle was withdrawn, and the catheter
      was fixed. The catheter was removed on the morning of the first postoperative
      day. When the patients started to feel pain during or after surgery, 2 mL of
      local anesthetic were re-injected through the catheter. RESULTS: During surgery,
      12 (27.9%) patients received a pain-free re-injection through the retrobulbar
      catheter resulting in a marked reduction of pain. Two (4.7%) patients needed a
      second re-injection. In the postoperative period, 23 (53.5%) patients experienced
      pain of grade 3 or higher 5.4 +/- 6.7 hr after start of surgery and received a
      retrobulbar re-injection. Eleven (25.6%) patients asked for a second
      postoperative re-injection, and four (9.3%) patients received a third
      postoperative re-injection. Cardiopulmonary and central nervous adverse effects
      were not noticed. CONCLUSIONS: Use of an ultra-fine retrobulbar catheter for
      repeat intraoperative and postoperative injections of local anesthetics is a
      simple and effective method to achieve analgesia during and after scleral
      buckling procedures.

PMID- 11983665
TI  - Epidural analgesia does not prolong the third stage of labour.
AB  - PURPOSE: To investigate whether there is an association between epidural
      analgesia and duration of third stage of labour, and between epidural analgesia
      and type of placental delivery (spontaneous vs expressed vs manual). METHODS: We
      examined, retrospectively, the computerized labour and delivery data of all 7,468
      parturients who had vaginal deliveries from 1996 to 1999 at the Civic Campus of
      the Ottawa Hospital. RESULTS: There was no difference in duration of third stage
      of labour between women with and without epidural pain relief who had spontaneous
      or expressed (fundal pressure/gentle cord traction) placental delivery. Duration
      of third stage of labour was shorter in women with epidural analgesia requiring
      manual removal of placenta. (25.3 min vs 40.1 min, P < 0.0001). The incidence of
      expressed placental delivery or manual removal of placenta was not different
      between the groups. CONCLUSIONS: We conclude that there is no clinically
      important difference in duration of third stage of labour between women with or
      without epidural analgesia who have spontaneous placental delivery or placental
      expulsion with fundal pressure/gentle cord traction. However, duration of third
      stage of labour was shorter in women who received epidural analgesia and required
      manual removal of the placenta.

PMID- 11983666
TI  - Anesthetic management of a parturient with Ehlers Danlos syndrome type IV.
AB  - PURPOSE: To describe the anesthetic management of a parturient with Ehlers Danlos
      syndrome (EDS) type IV. CLINICAL FEATURES: A 29-yr-old pregnant woman with EDS
      type IV was seen in the Obstetric Anesthesia Pre-assessment Clinic at 30 weeks
      gestation. She had a history of vertebral artery dissection, resulting in a
      transient neurological deficit at 22 yr of age. She had a normal vaginal delivery
      with continuous epidural analgesia for the delivery of her first child at 27 yr
      of age, before the diagnosis of EDS was made. Recent fibroblast culture
      demonstrated the production of abnormal procollagen type III, which is
      pathognomonic for EDS type IV. The patient and obstetrician preferred a repeat
      vaginal birth with instrumental delivery in the second stage. Analgesia for
      labour and delivery was provided with a continuous epidural infusion of
      ropivacaine and fentanyl. She delivered a healthy female infant with the use of
      outlet forceps, without complications. CONCLUSION: A pre-delivery,
      multidisciplinary, individualized management plan is required in patients with
      EDS, a rare disease with variable clinical features. In the case described,
      continuous epidural analgesia was effective and associated with excellent
      maternal and fetal outcomes.

PMID- 11983667
TI  - Best evidence in anesthetic practice. Prognosis: cognitive function at hospital
      discharge predicts long-term cognitive function after coronary artery bypass
      surgery.

PMID- 11983668
TI  - A comprehensive strategy to avoid transesophageal echocardiography probe damage.
AB  - PURPOSE: To describe the factors predisposing to transesophageal echocardiography
      (TEE) probe damage and to propose a strategy aimed at preventing damage to the
      TEE probe. Description of equipment and procedures: Damage to the TEE probe can
      occur anywhere and anytime during use in the operating room (OR) or when the
      probe is not in use in the OR, such as in the cleaning room, during storage or
      during transport of the probe. The components of the strategy used in our
      institution to avoid probe damage are: 1) storage of the probe in a dedicated
      holder in the OR when it is not in use, 2) use of a lexan box in the OR to
      protect the probe connector, 3) use of a custom-made holder when the probe is
      inserted in the patient, 4) use of a dedicated holder for soiled TEE probe
      storage in the cleaning room and for subsequent probe storage. CONCLUSION: We
      describe a comprehensive strategy designed to decrease TEE probe damage and the
      associated expenses. Further studies will be required to determine the
      effectiveness of the proposed measures.

PMID- 11983669
TI  - The cricoid cartilage and the esophagus are not aligned in close to half of adult
      patients.
AB  - PURPOSE: To determine the frequency and degree of lateral displacement of the
      esophagus relative to the cricoid cartilage ("cricoid") using computed tomography
      (CT) images of normal necks. METHODS: Fifty-one cervical CT scans of clinically
      normal patients were reviewed retrospectively. Esophageal diameter, distance
      between the midline of the cricoid and the midline of the esophagus, and distance
      between the lateral border of the cricoid and the lateral border of the esophagus
      were measured. RESULTS: Lateral esophageal displacement was observed in 49%
      (25/51) of CT images. When present, the mean length of displaced esophagus
      relative to the midline of the cricoid was 3.3 mm +/- SD 1.3 mm. Of those with
      lateral displacement, 64% had esophageal displacement beyond the lateral border
      of the cricoid (mean 3.2 mm +/- SD 1.2 mm). There is a relatively normal
      distribution of the grouped measures of percentage of esophageal diameter that is
      displaced. Of those with displacement, 48% had over 15% of the total width of the
      esophagus displaced laterally and 20% had over 20% of the esophageal width
      displaced laterally. CONCLUSION: There is a 49% frequency of some degree of
      lateral displacement of the esophagus relative to the cricoid.

PMID- 11983670
TI  - Co-administration of alfentanil-propofol improves laryngeal mask airway insertion
      compared to fentanyl-propofol.
AB  - PURPOSE: Insertion of the laryngeal mask airway (LMA) requires sufficient depth
      of anesthesia to relax the jaw and obtund airway reflexes. Recent studies suggest
      that the short-acting opioid alfentanil provides the best insertion conditions.
      We therefore compared the insertion conditions following co-administration of
      alfentanil-propofol with more commonly used fentanyl-propofol. METHODS: One
      hundred forty ASA I or II patients, age 18-81 yr, requiring minor surgery were
      recruited. They were randomized to receive either alfentanil (10 microg x kg(-1);
      n = 73) or fentanyl (1 microg x kg(-1); n = 67) with propofol (2.5 mg x kg(-1))
      90 sec prior to LMA (size 3 or 4) insertion. A six variable (mouth opening, ease
      of insertion, swallowing, coughing, movement and laryngospasm) three-point (nil /
      partial / total) score was used to assess insertion conditions. Duration of post
      insertion apnea was recorded. Insertion conditions were compared using Chi-square
      for trends. RESULTS: The two groups were demographically similar. Mouth opening
      and ease of insertion were not improved with alfentanil co-administration.
      Alfentanil-propofol reduced the incidence of swallowing, gagging, movement and
      laryngospasm (P < 0.05), with 29% (alfentanil) compared to 45% (fentanyl) of
      patients responding (P = 0.05) to LMA insertion. Apnea [mean (SD)] following
      alfentanil lasted 154 (139) sec compared to 82 (61) sec following fentanyl (P =
      0.001). CONCLUSION: Co-administration of alfentanil-propofol provided better
      insertion conditions than fentanyl-propofol, though apnea was prolonged by 72
      sec.

PMID- 11983671
TI  - Toronto Critical Care Medicine Symposium report.

PMID- 11983672
TI  - High frequency jet ventilation is associated with increased levels of plasma
      alpha-atrial natriuretic peptide -- a preliminary study.
AB  - PURPOSE: To determine if high frequency jet ventilation (HFJV) influences the
      secretion of alpha-atrial natriuretic peptide (alpha- ANP). METHODS: Sixteen
      patients undergoing otolaryngeal surgery were studied. Nine patients were
      subjected to intermittent positive pressure ventilation (IPPV), and seven
      patients underwent HFJV. Blood samples were drawn for the measurement of plasma
      alpha-ANP levels and blood gases before anesthesia, and at 30-min after starting
      either type of ventilation. The study was started at 2:00 p.m., and was completed
      before surgery. The plasma concentration of alpha-ANP was assayed by
      radioimmunoassay. RESULTS: There were no significant differences in mean arterial
      pressure, heart rate, oxygenation index and PaCO(2) between the two groups. IPPV
      was not associated with any changes in plasma -ANP levels, whereas HFJV was
      associated with significantly increased plasma alpha-ANP levels (from 60.0 +/-
      5.7 pg x mL(-1) before anesthesia to 112.0 +/- 11.6 pg x mL(-1) after
      ventilation, P < 0.01). The urine output of the HFJV patients was significantly
      greater than that of the IPPV patients (P < 0.05). CONCLUSION: These preliminary
      results suggest that HFJV is associated with a significant increase in plasma ANP
      and in urine output in anesthetized patients.

PMID- 11983673
TI  - Introduction to advanced Web page design and Web-based interactivity (medical
      education Web page series -- part 5).

PMID- 11983674
TI  - Efficacy of a combined technique using the Trachlight together with direct
      laryngoscopy under simulated difficult airway conditions in 350 anesthetized
      patients.

PMID- 11983675
TI  - Positioning the double-lumen endobronchial tube.

PMID- 11983676
TI  - Cardiovascular responses to endotracheal intubation with the Bullard and the
      Macintosh laryngoscopes.

PMID- 11983677
TI  - Diagnosing endotracheal tube partial withdrawal vs cuff puncture.

PMID- 11983678
TI  - Gum elastic bougie-guided placement of the ProSeal laryngeal mask.

PMID- 11983679
TI  - Systemic effects of subcutaneous and topical epinephrine administration during
      burn surgery.

PMID- 11983680
TI  - Non-pharmacological relief of acute pain following total abdominal hysterectomy.

PMID- 11983681
TI  - A novel peroxide-induced calcium transient regulates interleukin-6 expression in
      cardiac-derived fibroblasts.
AB  - Reperfusion of ischemic myocardium leads to a local burst of free radicals,
      increased [Ca(2+)](i), and the release of proinflammatory cytokines. The purpose
      of this study was to determine whether brief exposure of cardiac fibroblasts to
      H(2)O(2) is associated with transient changes in [Ca(2+)](i) levels and whether
      this stimulus is sufficient to induce interleukin-6 (IL-6) expression. Cardiac
      derived fibroblasts were isolated from adult male rats and cultured under
      standard conditions. Individual coverslip-attached fibroblasts were loaded with
      the calcium probe Fura-2/AM and exposed to a single 3-min pulse of 100 microm
      H(2)O(2). In addition, low passage cultures were exposed to a pulse of H(2)O(2)
      and assayed for IL-6 expression. A brief exposure of H(2)O(2) led to a large
      intracellular Ca(2+) transient with a mean transient magnitude of 318 +/- 28 nm
      (mean +/- S.D., n = 12). Stimulation in the absence of [Ca(2+)](o) led to a 59%
      reduction in mean transient magnitude (129 +/- 23 nm, n = 10, p < 0.001), whereas
      pretreatment with the inositol 1,4,5-trisphosphate receptor blocker xestospongin
      C resulted in a 37% reduction (199 +/- 25 nm, n = 10, p < 0.01). Cells treated
      with xestospongin C and stimulated in the absence of [Ca(2+)](o) did not exhibit
      a Ca(2+) transient. Time-dependent IL-6 release was significantly elevated by 4 h
      (368 +/- 64 pg/mg protein, p < 0.01) and increased further by 24 h (1030 +/- 76
      pg/mg protein). The depletion of cellular Ca(2+) by pretreatment with
      thapsigargin in the absence of [Ca(2+)](o) attenuated H(2)O(2)-induced IL-6 mRNA
      expression while blocking protein release. These data show that the exposure of
      cardiac fibroblasts to a brief pulse of physiological levels of H(2)O(2) resulted
      in a large Ca(2+) transient with intracellular and extracellular Ca(2+)
      contributions. Furthermore, brief H(2)O(2) exposure led to calcium-dependent IL-6
      expression.

PMID- 11983682
TI  - Induction of neuronal differentiation by a peptide corresponding to the
      homophilic binding site of the second Ig module of the neural cell adhesion
      molecule.
AB  - NCAM plays a key role in neural development and plasticity-mediating cell
      adhesion and differentiation mainly through homophilic binding. Until recently,
      attempts to modulate neuronal differentiation and plasticity through NCAM have
      been impeded by the absence of small synthetic agonists mimicking homophilic
      interactions of NCAM. We show here that a peptide, P2, corresponding to a 12
      amino acid sequence localized in the FG loop of the second Ig module of NCAM,
      binds to the first Ig module, which is the natural binding partner of the second
      Ig module, with an apparent K(d) of 4.7 +/- 0.9 x 10(-6) m. P2 inhibits cell
      aggregation and induces neurite outgrowth from hippocampal neurons, maximal
      neuritogenic effect being obtained at a concentration of 0.8 microm. The
      neuritogenic effect was inhibited by preincubation of P2 with the recombinant
      NCAM-IgI. Both the length of P2 and the basic amino acid residues at the N and C
      termini are important for its neuritogenic activity. Treatment of hippocampal
      cultures with P2 results in induction of phosphorylation of the mitogen-activated
      protein kinases ERK1 and ERK2. Thus, P2 is a potent mimetic of NCAM, and
      therefore, an attractive compound for the development of drugs for the treatment
      of neurodegenerative diseases.

PMID- 11983683
TI  - Activation of JNK1, RSK2, and MSK1 is involved in serine 112 phosphorylation of
      Bad by ultraviolet B radiation.
AB  - The Bcl-2 family member Bad is a pro-apoptotic protein, and phosphorylation of
      Bad by cytokines and growth factors promotes cell survival in many cell types.
      Induction of apoptosis by UV radiation is well documented. However, little is
      known about UV activation of cell survival pathways. Here, we demonstrate that
      UVB induces Bad phosphorylation at serine 112 in JNK1, RSK2, and MSK1-dependent
      pathways. Inhibition of mitogen-activated protein (MAP) kinases including ERKs,
      JNKs, and p38 kinase by the use of their respective dominant negative mutant or a
      specific inhibitor for MEK1 or p38 kinase, PD98059 or SB202190, resulted in
      abrogation of UVB-induced phosphorylation of Bad at serine 112. Incubation of
      active MAP kinase members with Bad protein showed serine 112 phosphorylation of
      Bad by JNK1 only. However, activated RSK2 and MSK1, downstream kinases of ERKs
      and p38 kinase, respectively, also phosphorylated Bad at serine 112 in vitro.
      Cells from a Coffin-Lowry syndrome patient (deficient in RSK2) or expressing an N
      terminal or C-terminal kinase-dead mutant of MSK1 were defective for UVB-induced
      serine 112 phosphorylation of Bad. Furthermore, MAP kinase pathway-dependent
      serine 112 phosphorylation was shown to be required for dissociation of Bad from
      Bcl-X(L). These data illustrated that UVB-induced phosphorylation of Bad at
      serine 112 was mediated through MAP kinase signaling pathways in which JNK1,
      RSK2, and MSK1 served as direct mediators.

PMID- 11983684
TI  - Oxidation of Ikappa Balpha at methionine 45 is one cause of taurine chloramine
      induced inhibition of NF-kappa B activation.
AB  - A band shift of IkappaBalpha was observed in Western blots with Jurkat cells
      treated with 1 mm taurine chloramine (TauCl) for 1 h. TauCl treatment inhibited
      tumor necrosis factor alpha (TNFalpha)-initiated nuclear factor kappaB (NF
      kappaB) activation. TauCl did not inhibit either the upstream of IkappaB kinase
      (IKK) activation or IKK itself but did inhibit NF-kappaB activation induced by
      IKK overexpression. Deletion experiments showed that a TauCl modification site
      causing the band shift of IkappaBalpha is Met45. High performance liquid
      chromatography and mass spectrometry analyses of a small peptide containing Met45
      revealed that TauCl oxidizes Met45. A mutant of IkappaBalpha whose Met45 was
      converted to alanine did not generate a band shift upon TauCl treatment and
      degraded in response to TNFalpha stimulation. However, a reporter assay revealed
      that NF-kappaB-dependent luciferase expression was not fully recovered in cells
      transfected with this mutant. These results indicate that Met45 oxidation of
      IkappaBalpha is a molecular mechanism underlying the TauCl-induced inhibition of
      NF-kappaB activation. A similar band shift was observed when HL-60 cells
      expressing myeloperoxidase were treated with 100 microm hydrogen peroxide for 5
      min. When rat neutrophils were incubated with bacteria, intracellular taurine
      decreased interleukin-8 production. Therefore, taurine may help suppress
      excessive inflammatory reaction in neutrophils.

PMID- 11983685
TI  - Synergistic coactivator function by coactivator-associated arginine
      methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA
      binding transcriptional activators.
AB  - The androgen receptor (AR) binds to and activates transcription of specific genes
      in response to its cognate steroid hormone, dihydrotestosterone. Transcriptional
      activation by the DNA-bound AR is accomplished with the help of a variety of
      coactivator proteins. For example, the p160 coactivators bind directly to AR and
      recruit additional coactivators such as the histone acetyltransferase p300 and
      the histone methyltransferase CARM1. The current study tested whether CARM1 can
      cooperate with other types of coactivator proteins. Recently it was shown that
      beta-catenin can also bind directly to and serve as a coactivator for AR. Here it
      is shown that CARM1 binds to beta-catenin and can function in synergy with beta
      catenin and p300 as coactivators for AR. The methyltransferase activity of CARM1
      is important for its synergistic coactivator function with beta-catenin. The
      synergistic coactivator function of beta-catenin and CARM1 is not restricted to
      steroid receptors because these two coactivators can also act synergistically
      with another type of DNA binding transcriptional activator, LEF-1/TCF-4.

PMID- 11983686
TI  - Control of calcium homeostasis by angiotensin II in adrenal glomerulosa cells
      through activation of p38 MAPK.
AB  - Angiotensin II-induced activation of aldosterone secretion in adrenal glomerulosa
      cells is mediated by an increase of intracellular calcium. We describe here a new
      Ca2+-regulatory pathway involving the inhibition by angiotensin II of calcium
      extrusion through the Na+/Ca2+ exchanger. Caffeine reduced both the angiotensin
      II-induced calcium signal and aldosterone production in bovine glomerulosa cells.
      These effects were independent of cAMP or calcium release from intracellular
      stores. The calcium response to angiotensin II was more sensitive to caffeine
      than the response to potassium, suggesting that the drug interacts with a pathway
      specifically elicited by the hormone. In calcium-free medium, calcium returned
      more rapidly to basal levels after angiotensin II stimulation in the presence of
      caffeine. Thapsigargin had no effect on these kinetics, but diltiazem, which
      inhibits the Na+/Ca2+ exchanger, markedly reduced the rate of calcium decrease
      and abolished caffeine action. The involvement of this exchanger was supported by
      the effect of cell depolarization and of a reduction of extracellular sodium on
      the rate of calcium extrusion. We also determined the mechanism of angiotensin II
      action on the exchanger. Phorbol esters reduced the rate of calcium extrusion,
      which was increased by baicalein, an inhibitor of lipoxygenases, and by SB
      203580, an inhibitor of the p38 MAPK. Finally, we showed that angiotensin II
      acutely activates, in a caffeine-sensitive manner, p38 MAPK in glomerulosa cells.
      In conclusion, in bovine glomerulosa cells, the Na+/Ca2+ exchanger plays a
      crucial role in extruding calcium, and, by reducing its activity, angiotensin II
      influences the amplitude of the calcium signal. The hormone exerts its action on
      the exchanger through a caffeine-sensitive pathway involving the p38 MAPK and
      lipoxygenase products.

PMID- 11983687
TI  - Striatal enriched phosphatase 61 dephosphorylates Fyn at phosphotyrosine 420.
AB  - A family of protein tyrosine phosphatases enriched within the central nervous
      system called striatal enriched phosphatase (STEP) has been implicated in the
      regulation of the N-methyl-d-aspartate receptor. STEP(61), a membrane-associated
      isoform located in the postsynaptic densities (PSDs) of striatal neurons,
      contains two transmembrane domains, two proline-rich domains, and a kinase
      interacting motif. This study demonstrates that STEP(61) associates with Fyn, a
      member of the Src family kinases that is also enriched in PSDs. By using human
      embryonic kidney 293 cells for co-transfection, we determined that a substrate
      trapping variant (STEP(61) CS) binds to Fyn but not to other members of the Src
      family present in PSDs. In a complementary experiment, myc-tagged Fyn
      immunoprecipitates STEP(61) CS. STEP(61) binds to Fyn through one of its proline
      rich domains and the kinase-interacting motif domain, whereas Fyn binds to
      STEP(61) through its Src homology 2 domain and the unique N-terminal domain.
      STEP(61) CS pulls down Fyn when the Tyr(420) site is phosphorylated. In vitro,
      wild-type STEP(61) dephosphorylates Fyn at Tyr(420) but not at Tyr(531). These
      results suggest that STEP regulates the activity of Fyn by specifically
      dephosphorylating the regulatory Tyr(420) and may be one mechanism by which Fyn
      activity is decreased within PSDs.

PMID- 11983688
TI  - Inhibition of tumor necrosis factor-alpha -induced nuclear translocation and
      activation of NF-kappa B by dehydroxymethylepoxyquinomicin.
AB  - We previously designed and synthesized an NF-kappaB inhibitor,
      dehydroxymethylepoxyquinomicin (DHMEQ), that showed anti-inflammatory activity in
      vivo. In the present study we looked into its mechanism of inhibition. DHMEQ
      inhibited tumor necrosis factor-alpha (TNF-alpha)- and 12-O-tetradecanoylphorbol
      13-acetate-induced transcriptional activity of NF-kappaB in human T cell leukemia
      Jurkat cells. It also inhibited the TNF-alpha-induced DNA binding of nuclear NF
      kappaB but not the phosphorylation and degradation of IkappaB. Moreover, DHMEQ
      inhibited the TNF-alpha-induced nuclear accumulation of p65, a component of NF
      kappaB. It also inhibited TNF-alpha-induced nuclear transport of green
      fluorescent protein-tagged p65. On the other hand, DHMEQ did not inhibit the
      nuclear transport of Smad2 and large T antigen. Also, it did not inhibit TNF
      alpha-induced activation of JNK but synergistically induced apoptosis with TNF
      alpha in Jurkat cells. Taken together, these data indicate that DHMEQ is a unique
      inhibitor of NF-kappaB acting at the level of nuclear translocation.

PMID- 11983689
TI  - Reactions of the class II peroxidases, lignin peroxidase and Arthromyces ramosus
      peroxidase, with hydrogen peroxide. Catalase-like activity, compound III
      formation, and enzyme inactivation.
AB  - The reactions of the fungal enzymes Arthromyces ramosus peroxidase (ARP) and
      Phanerochaete chrysosporium lignin peroxidase (LiP) with hydrogen peroxide
      (H(2)O(2)) have been studied. Both enzymes exhibited catalase activity with
      hyperbolic H(2)O(2) concentration dependence (K(m) approximately 8-10 mm, k(cat)
      approximately 1-3 s(-1)). The catalase and peroxidase activities of LiP were
      inhibited within 10 min and those of ARP in 1 h. The inactivation constants were
      calculated using two independent methods; LiP, k(i) approximately 19 x 10(-3) s(
      1); ARP, k(i) approximately 1.6 x 10(-3) s(-1). Compound III (oxyperoxidase) was
      detected as the majority species after the addition of H(2)O(2) to LiP or ARP,
      and its formation was accompanied by loss of enzyme activity. A reaction scheme
      is presented which rationalizes the turnover and inactivation of LiP and ARP with
      H(2)O(2). A similar model is applicable to horseradish peroxidase. The scheme
      links catalase and compound III forming catalytic pathways and inactivation at
      the level of the [compound I.H(2)O(2)] complex. Inactivation does not occur from
      compound III. All peroxidases studied to date are sensitive to inactivation by
      H(2)O(2), and it is suggested that the model will be generally applicable to
      peroxidases of the plant, fungal, and prokaryotic superfamily.

PMID- 11983690
TI  - beta -Amyloid peptide activates alpha 7 nicotinic acetylcholine receptors
      expressed in Xenopus oocytes.
AB  - The alpha7 nicotinic acetylcholine receptor is highly expressed in hippocampus
      and in cholinergic projection neurons from the basal forebrain, structures that
      are particularly vulnerable to the ravages of Alzheimer's disease. Previous work
      suggests that beta-amyloid peptide can interact with alpha7 nicotinic
      acetylcholine receptors, although the nature of this interaction has not been
      well characterized. To test whether beta-amyloid peptide can activate alpha7
      nicotinic acetylcholine receptors, we expressed these receptors in Xenopus
      oocytes and performed two-electrode voltage clamp recordings, characterizing the
      response to beta-amyloid peptide 1-42 applied at concentrations ranging from 1 pm
      to 100 nm. In alpha7-expressing oocytes, beta-amyloid peptide 1-42 elicits inward
      currents at low concentrations (1-100 pm), whereas at higher concentrations (nm),
      less effective receptor activation is observed, indicative of receptor
      desensitization. Preincubation with the alpha7-selective agents, the antagonist
      methyllycaconatine, and the agonist 4-OH-GTS-21 blocked beta-amyloid peptide
      induced receptor activation. beta-amyloid peptide 1-42 at low concentrations was
      able to activate the L250T mutant alpha7 receptor. The endogenous Ca(2+)
      activated chloride current in Xenopus oocytes is recruited upon receptor
      activation since replacing Ca(2+) with Ba(2+) in the recording solution reduced
      current amplitude. Thus, when beta-amyloid peptide activation of alpha7 receptors
      occurs, these currents are comprised, at least in part, of Ca(2+).

PMID- 11983691
TI  - Novel mode of interference with nuclear factor of activated T-cells regulation in
      T-cells by the bacterial metabolite n-butyrate.
AB  - The transcription factor nuclear factor of activated T-cells (NF-AT) plays an
      essential role in the activation of many early immune response genes. A dynamic
      equilibrium between calcineurin and cellular kinases controls its phosphorylation
      and thus regulates its activity by determining its subcellular localization.
      Here, we demonstrate that T-cell activation in the presence of the bacterial
      metabolite n-butyrate, which leads to inhibition of interleukin-2 transcription,
      is characterized by the maintenance of the activity of counter-regulatory kinases
      glycogen synthase kinase 3 and protein kinase A as well as persistence of
      intracellular cAMP levels, whereas calcium response and mitogen-activated protein
      kinase activation were indistinguishable from cells stimulated in the absence of
      n-butyrate. Nuclear binding of NF-AT was decreased but other transcription
      factors implicated in interleukin-2 expression such as AP1 and nuclear factor
      kappaB were unaffected. The effect on NF-AT binding appeared to be the result of
      increased nuclear export because the export inhibitor leptomycin B completely
      restored nuclear binding of NF-AT. We, therefore, provide first evidence for
      interference with NF-AT regulation alternative to the currently understood
      inhibition of nuclear import. This mechanism might represent a bacterial strategy
      to subvert host defense, which could be of particular clinical importance in the
      gastrointestinal tract where high amounts of n-butyrate are physiologically
      present.

PMID- 11983692
TI  - A monomeric L-aspartase obtained by in vitro selection.
AB  - By mimicking the partial spatial structure of the dimer of the l-aspartase
      subunit, the central ten-helix bundle, and an "active site" between the cleft of
      domain 1 (D1) and domain 3 (D3) from different subunits, we designed l-aspartase
      variants, in which D1D2 and D2D3 were ligated with a random hexapeptide loop. As
      expected, we obtained the variant with the highest activity (relative activity is
      21.3% of the native enzyme, named as drAsp017) by in vitro selection. The
      molecular weight of this variant, obtained from size-exclusion column
      chromatography, is about 81 kDa, which indicates that it is indeed a monomer,
      whereas native l-aspartase is a tetramer. The activity-reversibility of drAsp017
      (10(-7) m) was 80% after incubation for 30 min at 50 degrees C, while native
      enzyme only retained about 17% under the same conditions. Reactivation of
      drAsp017 denatured in 4 m guanidine HCl was independent of protein concentration
      at up to 20 x 10(-8) m at 25 degrees C, whereas the protein concentration of
      native enzyme strongly affected its reactivation under the above conditions. The
      sensitivity of drAsp017 (10(-7) m) to effective factors in the fumarate-amination
      reaction compared with native enzyme was also determined. Half-saturating
      concentrations of the activator l-aspartate and Mg2+ for drAsp017 (0.8 and 0.5
      mm, respectively) are much higher than that of the native enzyme (0.10 and 0.15
      mm, respectively). The data show that a monomeric l-aspartase is obtained by in
      vitro selection. Thus, the conversion of oligomeric proteins into their
      functional monomers could have important applications.

PMID- 11983693
TI  - Opposite regulation of type II and III receptors for immunoglobulin G in mouse
      glomerular mesangial cells and in the induction of anti-glomerular basement
      membrane (GBM) nephritis.
AB  - We examined the capacity of mouse glomerular mesangial cells (MC) to express and
      function through two different low affinity FcgammaRs, the activating FcgammaRIII
      and the inhibitory FcgammaRII. Immunohistochemistry identified FcgammaRII as the
      prominent FcgammaR in the kidney, and low levels of FcgammaRIIb2-specific mRNA
      were also detected in primary cultures of growth-arrested MC. Activation by tumor
      necrosis factor-alpha/interleukin-1beta induced substantial FcgammaRII expression
      in proliferating MC. Importantly, however, stimulation with interferon-gamma (IFN
      gamma)/lipopolysaccharide or IFN-gamma alone resulted in a complete down
      regulation of FcgammaRII, which was accompanied by a strong increase in FcRgamma
      chain mRNA and a surface appearance of FcgammaRIII. Activating FcgammaRIII
      triggered mRNA synthesis for monocyte chemoattractant protein-1 (MCP-1), MCP-5,
      cytokine-induced neutrophil chemoattractant, and RANTES, whereas FcgammaRIII
      deficient MC failed to respond to immune complex (IC) activation as shown by
      impaired production of MCP-1 mRNA/protein. In a passive model of acute anti
      glomerular basement membrane (GBM) nephritis, induction of FcgammaRIII and
      suppression of FcgammaRII occurred in kidney tissues. Blockade of FcgammaRII,
      when induced selectively in the kidney, resulted in enhanced inflammation. Taken
      together, our results define a novel regulatory pathway with opposite regulation
      of FcgammaRII (suppressed) and FcgammaRIII (induced) by IFN-gamma on MCs in vitro
      and anti-GBM IgG in vivo. Herein is provided the first evidence that glomerular
      FcgammaRII plays an important immunoregulatory role in the initiation of IC
      glomerulonephritis.

PMID- 11983694
TI  - Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine
      845 is required for zinc-induced Ras activation.
AB  - Previous studies have shown that exposure of cells to Zn2+ ions induces Ras and
      MAPK activation through the EGF receptor (EGFR). To further determine the role of
      EGFR in Zn2+-induced signaling, mouse B82L fibroblasts expressing no detectable
      EGFR protein (B82L-par), wild type EGFR (B82L-wt), kinase-deficient EGFR (B82L
      K721M), or COOH-truncated EGFR (B82L-c'958) were tested. Exposure to Zn2+ induced
      Ras activity in B82L-wt, B82L-K721M, and B82L-c'958 but not in B82L-par cells,
      indicating that the tyrosine kinase domain and the auto-phosphorylation sites of
      the EGFR were not required for Zn2+-induced Ras activation. Zn2+ induced Src
      activation in all B82L cell lines, including B82L-par, indicating that Src
      activation is independent of the presence of the EGFR. A Src kinase inhibitor
      blocked Zn2+-induced Ras activation in all the B82L cell lines capable of this
      response, suggesting the involvement of Src kinase in Zn2+-induced Ras activation
      via the EGFR. Zn2+ induced the association of the EGFR with Src and specifically
      increased the phosphorylation of EGFR at tyrosine 845 (Tyr-845), a known Src
      phosphorylation site. Stably transfected B82L cells with a point mutation of the
      EGFR at Tyr-845 (B82L-Y845F) exhibited only basal Ras activity following exposure
      to Zn2+. These data demonstrate that Src-dependent phosphorylation of the EGFR at
      Tyr-845 is required for EGFR transactivation and Zn2+-induced Ras activation.

PMID- 11983695
TI  - Arginine residue at position 573 in Enterococcus hirae vacuolar-type ATPase NtpI
      subunit plays a crucial role in Na+ translocation.
AB  - The 76-kDa NtpI subunit constitutes the membrane-embedded V(0) moiety of
      Enterococcus hirae vacuolar type Na+-ATPase with a 16-kDa NtpK hexamer containing
      Na+ binding sites. In this study, we investigated the role of an arginine
      residue, which is highly conserved among the corresponding subunits of bacterial
      vacuolar-type ATPases, at position 573 of NtpI. Substitution of Glu, Leu, or Gln
      for Arg-573 abolished sodium transport and sodium-stimulated ATP hydrolysis of
      the enzyme. The conservative replacement of Arg by Lys lowered both activities
      about one-fifth of those of the wild type enzyme. We have reported previously on
      ATP-dependent negative cooperativity for Na+ coupling of this enzyme (Murata, T.,
      Kakinuma, Y., and Yamato, I. (2001) J. Biol. Chem. 276, 48337-48340). The
      negative cooperativity for the Na+ dependence of ATPase activity was weakened by
      the mutation R573K; the Hill coefficients for the wild type and mutant enzymes at
      a saturated ATP concentration were 0.22 +/- 0.03 and 0.40 +/- 0.05, respectively.
      The Hill coefficients of both enzymes at limited ATP concentrations approached 1.
      These results indicate that NtpI Arg-573 is indispensable for sodium
      translocation and for the cooperative features of E. hirae vacuolar-type ATPase.

PMID- 11983696
TI  - The four-helix bundle of the neuronal target membrane SNARE complex is neither
      disordered in the middle nor uncoiled at the C-terminal region.
AB  - Assembly of the SNARE complex is an essential step for membrane fusion and
      neurotransmitter release in neurons. The plasma membrane SNAREs syntaxin 1A and
      SNAP-25 (t-SNAREs) and the delivery-vesicle SNARE VAMP2 (or v-SNARE) contain the
      "SNARE regions" that essentially mediate SNARE pairing. Using site-directed spin
      labeling and EPR distance measurement we show that two identical copies of the
      SNARE region from syntaxin 1A intertwine as a coiled coil near the "ionic layer"
      region. The structure of the t-SNARE complex appears to be virtually identical to
      that of the ternary SNARE complex, except that VAMP2 is substituted to the second
      copy of syntaxin 1A. Furthermore, it appears that the coiled coil structure is
      maintained up to residue 259 of syntaxin 1A, identical to that of the ternary
      complex. These results are somewhat contradictory to the previous reports,
      suggesting that the t-SNARE complex has the disordered midsection (Xiao, W. Z.,
      Poirier, M. A., Bennett, M. K., and Shin, Y. K. (2001) Nat. Struc. Biol. 8, 308
      311) and the uncoiled C-terminal region (Margittai, M., Fasshauer, D., Pabst, S.,
      Jahn, R., and Langen, R. (2001) J. Biol. Chem. 276, 13169-13177). The newly
      refined structure of the t-SNARE complex provides a basis for the better
      understanding of the SNARE assembly process. It also provides possible structural
      functional clues to the membrane fusion in the v-SNARE deleted fusion models.

PMID- 11983697
TI  - The transcriptional activation function of the HIF-like factor requires
      phosphorylation at a conserved threonine.
AB  - The hypoxia-inducible factor (HIF)-1alpha and the HIF-like factor (HLF)
      transcription factors are regulated at multiple levels including protein
      stabilization, nuclear import, and activation of transactivation, resulting in
      recruitment of coactivators such as the cAMP-response element-binding protein
      (CREB)-binding protein (CBP)/p300 and SRC-1. During low oxygen tension these
      proteins modulate a network of genes that are necessary for angiogenesis,
      erythropopoiesis, and glycolysis. We report here that the C-terminal
      transactivation domain of HLF is phosphorylated on multiple sites and that
      phosphorylation on threonine 844 of HLF is necessary for the transcriptional
      activation function of the protein independently of the hypoxia condition.
      Importantly, using the mammalian two-hybrid system we demonstrate that a
      substitution of threonine 844 to an alanine decreased the enhanced
      transcriptional activation function mediated by CBP/p300.

PMID- 11983698
TI  - Angiotensin II inhibits human trophoblast invasion through AT1 receptor
      activation.
AB  - Trophoblast implantation depends, in part, on the controlled production of
      plasmin from plasminogen, a process regulated by plasminogen activators and
      plasminogen activator inhibitors. We have determined that angiotensin II (Ang II)
      stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in
      human trophoblasts in a time- and concentration-dependent manner. Our results
      indicate that Ang II activates PAI-1 gene expression through the AT1 receptor and
      involves the calcium-dependent activation of calcineurin and the nuclear
      translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with
      reduced trophoblast invasion as judged by an in vitro invasion assay. These
      studies are the first to link the renin-angiotensin system with the fibrinolytic
      system to regulate trophoblast invasion.

PMID- 11983699
TI  - Expression of the human poliovirus receptor/CD155 gene is activated by sonic
      hedgehog.
AB  - The human poliovirus receptor/CD155 is a transmembrane glycoprotein belonging to
      the immunoglobulin superfamily. The ectodomain of CD155 mediates cell attachment
      to the extracellular matrix molecule vitronectin, while its intracellular domain
      interacts with the dynein light chain Tctex-1. CD155 is a primate-restricted gene
      that is expressed during development in mesenchymal tissues and ventrally derived
      structures within the CNS. Its function in adults is as yet unknown, but
      significantly, CD155 is aberrantly expressed in neuroectodermal tumors. We show
      that the expression of CD155 mRNA is up-regulated when human Ntera2 cells are
      treated with purified Sonic hedgehog (Shh) protein. Reporter gene expression
      driven by the CD155 core promoter is activated by Shh in transient co
      transfection assays. Analysis of the CD155 core promoter indicates that an intact
      GLI binding site is required for Shh activation. In addition, overexpression of
      Gli1 or Gli3 potently activates reporter gene expression driven by the CD155 core
      promoter. These data identify the CD155 gene as a transcriptional target of Shh,
      a finding that has significance for the normal function of CD155 during
      development and the expression of CD155 in neuroectodermal tumors.

PMID- 11983700
TI  - A metal-binding member of the late embryogenesis abundant protein family
      transports iron in the phloem of Ricinus communis L.
AB  - The transport of metal micronutrients to developing organs in a plant is mediated
      primarily by the sieve elements. Ligands are thought to form complexes with the
      free ions in order to prevent cellular damage, but no binding partners have been
      unequivocally identified from plants so far. This study has used the phloem
      mediated transport of micronutrients during the germination of the castor bean
      seedling to identify an iron transport protein (ITP). It is demonstrated that
      essentially all (55)Fe fed to seedlings is associated with the protein fraction
      of phloem exudate. It is shown that ITP carries iron in vivo and binds additional
      iron in vitro. ITP was purified to homogeneity from minute amounts of phloem
      exudate using immobilized metal ion affinity chromatography. It preferentially
      binds to Fe(3+) but not to Fe(2+) and also complexes Cu(2+), Zn(2+), and Mn(2+)
      in vitro. The corresponding cDNA of ITP was cloned using internal peptide
      fragments. The deduced protein of 96 amino acids shows high similarity to the
      stress-related family of late embryogenesis abundant proteins. Its predicted
      characteristics and its RNA expression pattern are consistent with a function in
      metal ion binding. The ITP from Ricinus provides the first identified
      micronutrient binding partner for phloem-mediated long distance transport in
      plants and is the first member of the late embryogenesis abundant protein family
      shown to have such a function.

PMID- 11983701
TI  - Increase in cytosolic Ca2+ levels through the activation of non-selective cation
      channels induced by oxidative stress causes mitochondrial depolarization leading
      to apoptosis-like death in Leishmania donovani promastigotes.
AB  - Reactive oxygen species are important regulators of protozoal infection.
      Promastigotes of Leishmania donovani, the causative agent of Kala-azar, undergo
      an apoptosis-like death upon exposure to H2O2. The present study shows that upon
      activation of death response by H2O2, a dose- and time-dependent loss of
      mitochondrial membrane potential occurs. This loss is accompanied by a depletion
      of cellular glutathione, but cardiolipin content or thiol oxidation status
      remains unchanged. ATP levels are reduced within the first 60 min of exposure as
      a result of mitochondrial membrane potential loss. A tight link exists between
      changes in cytosolic Ca2+ homeostasis and collapse of the mitochondrial membrane
      potential, but the dissipation of the potential is independent of elevation of
      cytosolic Na+ and mitochondrial Ca2+. Partial inhibition of cytosolic Ca2+
      increase achieved by chelating extracellular or intracellular Ca2+ by the use of
      appropriate agents resulted in significant rescue of the fall of the
      mitochondrial membrane potential and apoptosis-like death. It is further
      demonstrated that the increase in cytosolic Ca2+ is an additive result of release
      of Ca2+ from intracellular stores as well as by influx of extracellular Ca2+
      through flufenamic acid-sensitive non-selective cation channels; contribution of
      the latter was larger. Mitochondrial changes do not involve opening of the
      mitochondrial transition pore as cyclosporin A is unable to prevent mitochondrial
      membrane potential loss. An antioxidant like N-acetylcysteine is able to inhibit
      the fall of the mitochondrial membrane potential and prevent apoptosis-like
      death. Together, these findings show the importance of non-selective cation
      channels in regulating the response of L. donovani promastigotes to oxidative
      stress that triggers downstream signaling cascades leading to apoptosis-like
      death.

PMID- 11983702
TI  - STARS, a striated muscle activator of Rho signaling and serum response factor
      dependent transcription.
AB  - Changes in actin dynamics influence diverse cellular processes and couple the
      actin-based cytoskeleton to changes in gene transcription. Members of the Rho
      GTPase family regulate cytoskeletal organization by stimulating actin
      polymerization and stress fiber formation when activated by extracellular
      signaling. The transcriptional activity of serum response factor (SRF) is
      stimulated in response to changes in actin dynamics and Rho signaling, but the
      proteins that mediate this phenomenon have not been fully identified. We describe
      a novel, evolutionarily conserved actin-binding protein, called STARS (striated
      muscle activator of Rho signaling), that is expressed specifically in cardiac and
      skeletal muscle cells. STARS binds to the I-band of the sarcomere and to actin
      filaments in transfected cells, where it activates Rho-signaling events. STARS
      stimulates the transcriptional activity of SRF through a mechanism that requires
      actin binding and involves Rho GTPase activation. STARS provides a potential
      mechanism for specifically enhancing Rho-dependent transcription in muscle cells
      and for linking changes in actin dynamics to gene transcription.

PMID- 11983703
TI  - Crystal structure and biochemical characterization of human kallikrein 6 reveals
      that a trypsin-like kallikrein is expressed in the central nervous system.
AB  - The human kallikreins are a large multigene family of closely related serine-type
      proteases. In this regard, they are similar to the multigene kallikrein families
      characterized in mice and rats. There is a much more extensive body of knowledge
      regarding the function of mouse and rat kallikreins in comparison with the human
      kallikreins. Human kallikrein 6 has been proposed as the homologue to rat
      myelencephalon-specific protease, an arginine-specific degradative-type protease
      abundantly expressed in the central nervous system and implicated in
      demyelinating disease. We present the x-ray crystal structure of mature, active
      recombinant human kallikrein 6 at 1.75-A resolution. This high resolution model
      provides the first three-dimensional view of one of the human kallikreins and one
      of only a few structures of serine proteases predominantly expressed in the
      central nervous system. Enzymatic data are presented that support the
      identification of human kallikrein 6 as the functional homologue of rat
      myelencephalon-specific protease and are corroborated by a molecular phylogenetic
      analysis. Furthermore, the x-ray data provide support for the characterization of
      human kallikrein 6 as a degradative protease with structural features more
      similar to trypsin than the regulatory kallikreins.

PMID- 11983704
TI  - Biochemical and genetic analyses of yeast and human high affinity copper
      transporters suggest a conserved mechanism for copper uptake.
AB  - The redox active metal copper is an essential cofactor in critical biological
      processes such as respiration, iron transport, oxidative stress protection,
      hormone production, and pigmentation. A widely conserved family of high affinity
      copper transport proteins (Ctr proteins) mediates copper uptake at the plasma
      membrane. However, little is known about Ctr protein topology, structure, and the
      mechanisms by which this class of transporters mediates high affinity copper
      uptake. In this report, we elucidate the topological orientation of the yeast
      Ctr1 copper transport protein. We show that a series of clustered methionine
      residues in the hydrophilic extracellular domain and an MXXXM motif in the second
      transmembrane domain are important for copper uptake but not for protein sorting
      and delivery to the cell surface. The conversion of these methionine residues to
      cysteine, by site-directed mutagenesis, strongly suggests that they coordinate to
      copper during the process of metal transport. Genetic evidence supports an
      essential role for cooperativity between monomers for the formation of an active
      Ctr transport complex. Together, these results support a fundamentally conserved
      mechanism for high affinity copper uptake through the Ctr proteins in yeast and
      humans.

PMID- 11983705
TI  - Constitutive activation of angiotensin II type 1 receptor alters the orientation
      of transmembrane Helix-2.
AB  - A key step in transmembrane (TM) signal transduction by G-protein-coupled
      receptors (GPCRs) is the ligand-induced conformational change of the receptor,
      which triggers the activation of a guanine nucleotide-binding protein. GPCRs
      contain a seven-TM helical structure essential for signal transduction in
      response to a large variety of sensory and hormonal signals. Primary structure
      comparison of GPCRs has shown that the second TM helix contains a highly
      conserved Asp residue, which is critical for agonist activation in these
      receptors. How conformational changes in TM2 relate to signal transduction by a
      GPCR is not known, because activation-induced conformational changes in TM2 helix
      have not been measured. Here we use modification of reporter cysteines to measure
      water accessibility at specific residues in TM2 of the type 1 receptor for the
      octapeptide hormone angiotensin II. Activation-dependent changes in the
      accessibility of Cys76 on TM2 were measured in constitutively activated mutants.
      These changes were directly correlated with measurement of function, establishing
      the link between physical changes in TM2 and function. Accessibility changes were
      measured at several consecutive residues on TM2, which suggest that TM2 undergoes
      a transmembrane movement in response to activation. This is the first report of
      in situ measurement of TM2 movement in a GPCR.

PMID- 11983706
TI  - Glucose regulates insulin mitogenic effect by modulating SHP-2 activation and
      localization in JAr cells.
AB  - The glucose effect on cell growth has been investigated in the JAr human
      choriocarcinoma cells. When JAr cells were cultured in the presence of 6 mm
      glucose (LG), proliferation and thymidine incorporation were induced by serum,
      epidermal growth factor, and insulin-like growth factor 1 but not by insulin. In
      contrast, at 25 mm glucose (HG), proliferation and thymidine incorporation were
      stimulated by insulin, serum, epidermal growth factor, and insulin-like growth
      factor 1 to a comparable extent, whereas basal levels were 25% lower than those
      in LG. HG culturing also enhanced insulin-stimulated insulin receptor and insulin
      receptor substrate 1 (IRS1) tyrosine phosphorylations while decreasing basal
      phosphorylations. These actions of glucose were accompanied by an increase in
      cellular tyrosine phosphatase activity. The activity of SHP-2 in HG-treated JAr
      cells was 400% of that measured in LG-treated cells. SHP-2 co-precipitation with
      IRS1 was also increased in HG-treated cells. SHP-2 was mainly cytosolic in LG
      treated cells. However, HG culturing largely redistributed SHP-2 to the internal
      membrane compartment, where tyrosine-phosphorylated IRS1 predominantly localizes.
      Further exposure to insulin rescued SHP-2 cytosolic localization, thereby
      preventing its interaction with IRS1. Antisense inhibition of SHP-2 reverted the
      effect of HG on basal and insulin-stimulated insulin receptor and IRS1
      phosphorylation as well as that on thymidine incorporation. Thus, in JAr cells,
      glucose modulates insulin mitogenic action by modulating SHP-2 activity and
      intracellular localization.

PMID- 11983707
TI  - The p38 and JNK pathways cooperate to trans-activate vitamin D receptor via c
      Jun/AP-1 and sensitize human breast cancer cells to vitamin D(3)-induced growth
      inhibition.
AB  - The signaling connection between mitogen-activated protein kinases(MAPKs) and
      nuclear steroid receptors is complex and remains mostly unexplored. Here we
      report that stress-activated protein kinases p38 and JNK trans-activate nuclear
      steroid vitamin D receptor (VDR) gene and increase vitamin D(3)-dependent growth
      inhibition in human breast cancer cells. Activation of p38 and JNK by an active
      MAPK kinase 6 stimulates VDR promoter activity independently of the ligand
      vitamin D(3) and estrogen receptor expression. Moreover, stimulation of the
      endogenous stress pathways by adenovirus-mediated delivery of recombinant MAPK
      kinase 6 also activates VDR and sensitizes MCF-7 cells to vitamin D(3)-dependent
      growth inhibition. Both the p38 and JNK MAPK pathways and the downstream
      transcription factor c-Jun/AP-1 are required for the VDR stimulation, as revealed
      by application of their dominant negatives, the specific p38 inhibitor SB203580,
      and site-directed mutagenesis of the AP-1 element in the VDR promoter. The
      essential role of the p38 and JNK stress pathways in up-regulation of VDR
      expression is further confirmed by using the chemical stimulator arsenite. These
      results establish a signaling connection between the stress MAPK pathways and
      steroid hormone receptor VDR expression and thereby offer new insights into
      regulation of cell growth by the MAPK pathways through regulation of vitamin
      D(3)/VDR activity.

PMID- 11983708
TI  - Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs
      early cardiac gene activity.
AB  - Herein, the restricted expression of serum response factors (SRF) closely
      overlapped with Nkx2-5 and GATA4 transcripts in early chick embryos coinciding
      with the earliest appearance of cardiac alpha-actin (alphaCA) transcripts and
      nascent myocardial cells. The combinatorial expression of SRF, a MADS box factor
      Nkx2-5 (a NK4 homeodomain), and/or GATA4, a dual C4 zinc finger protein, in
      heterologous CV1 fibroblasts and Schneider 2 insect cells demonstrated
      synergistic induction of alphaCA promoter activity. These three factors induced
      endogenous alphaCA mRNA over a 100-fold in murine embryonic stem cells. In
      addition, the DNA-binding defective mutant Nkx2-5pm efficiently coactivated the
      alphaCA promoter in the presence of SRF and GATA4 in the presence of all four
      SREs and was substantially weakened when individual SREs were mutated and or
      serially deleted. In contrast, the introduction of SRFpm, a SRF DNA-binding
      mutant, blocked the activation with all of the alphaCA promoter constructions.
      These assays indicated a dependence upon cooperative SRF binding for facilitating
      the recruitment of Nkx2-5 and GATA4 to the alphaCA promoter. Furthermore, the
      recruitment of Nkx2-5 and GATA4 by SRF was observed to strongly enhance SRF DNA
      binding affinity. This mechanism allowed for the formation of higher ordered
      alphaCA promoter DNA binding complexes, led to a model of SRF physical
      association with Nkx2-5 and GATA4.

PMID- 11983709
TI  - GRP94-associated enzymatic activities. Resolution by chromatographic
      fractionation.
AB  - GRP94 (gp96), which performs established functions as a molecular chaperone and
      immune system modulator, has been reported to display a number of intrinsic
      enzymatic activities, including ATP hydrolysis, protein phosphorylation, and
      aminopeptidase. In observing that GRP94 co-purified with bacterial beta
      galactosidase through multiple chromatographic steps, we have examined the
      hypothesis that the reported enzymatic activities of GRP94 may reflect co
      purification of contaminant enzymes, rather than intrinsic catalytic functions.
      In subjecting GRP94 to increasingly stringent chromatographic purification, we
      report that a GRP94 carboxyl-terminal directed protein kinase activity could be
      separated from GRP94 by heparin affinity chromatography. Analysis of the kinase
      substrate specificity indicates that this kinase is distinct from casein kinase
      II, which is known to co-purify with GRP94. Electrophoretically pure GRP94
      displayed low, but significant levels of aminopeptidase activity. Further
      purification of GRP94 by anion exchange and heparin affinity chromatography
      yielded resolution of GRP94 from the aminopeptidase activity. Furthermore,
      exhaustive trypsinolysis of GRP94 preparations displaying aminopeptidase activity
      yielded complete proteolysis of GRP94 but did not affect aminopeptidase activity.
      These results are discussed with respect to current models for GRP94 function and
      the role of such co-purifying (poly)peptides in the generation of GRP94-dependent
      cellular immune responses.

PMID- 11983710
TI  - Identification of the tRNA-dihydrouridine synthase family.
AB  - 5,6-Dihydrouridine (D) is a modified base found abundantly in the D-loops of tRNA
      from Archaea, Bacteria, and Eukarya. D is thought to be formed post
      transcriptionally by the reduction of uridines in tRNA transcripts. Despite its
      abundance, no enzymes that catalyze D-formation have been identified. Using
      comparative genomics and computational methods we have identified members of the
      cluster of orthologous genes, COG0042, as putative dihydrouridine synthase
      encoding genes. Escherichia coli contains three COG0042 family members (yjbN,
      yhdG, and yohI). Strains were created where one, two, or all three of the COG0042
      genes were deleted. Purified tRNA samples were investigated from the three single
      and the three double knockout strains, as well as from the triple deletion
      strain. The results showed that the COG0042 gene family is responsible for tRNA
      dihydrouridine synthase activity in E. coli. They also suggest that the COG0042
      encoded family members act site-specifically on the tRNA D-loop and contain non
      redundant catalytic functions in vivo.

PMID- 11983711
TI  - Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox
      cycling. Implications for studies of Hsp90 and endothelial cell nitric-oxide
      synthase.
AB  - The ansamycin antibiotic geldanamycin has frequently been used as an inhibitor of
      heat shock protein 90 (Hsp90), and this agent has been widely employed as a probe
      to examine the interactions of Hsp90 with endothelial nitric-oxide synthase.
      Geldanamycin contains a quinone group, which may participate in redox cycling.
      When geldanamycin was exposed to the flavin-containing enzyme cytochrome P-450
      reductase, both semiquinone and superoxide (O(2)(*)(-)) radicals were detected
      using electron spin resonance. The treatment of endothelial cells with
      geldanamycin resulted in a dramatic increase in O(2)(*)(-) generation, which was
      independent of endothelial nitric-oxide synthase, because it was not inhibited by
      N-nitro-l-arginine methyl ester and also occurred in vascular smooth muscle
      cells. Diphenylene iodinium inhibited this increase in O(2)(*)(-) by 50%,
      suggesting that flavin-containing enzymes are involved in geldanamycin-induced
      O(2)(*)(-) generation. In the absence of cells, geldanamycin directly oxidized
      ascorbate, consumed oxygen, and produced O(2)(*)(-). Geldanamycin decreased the
      bioavailable nitric oxide generated by 3,4-dihydrodiazete 1,2-dioxide in smooth
      muscle cells by 50%, whereas pretreatment with superoxide dismutase inhibited the
      effect of geldanamycin. These findings demonstrate that geldanamycin generates
      O(2)(*)(-), which scavenges nitric oxide, leading to loss of its bioavailability.
      This effect is independent of the inhibition of Hsp90 and indicates that
      geldanamycin cannot be used as a specific inhibitor of Hsp90. In light of these
      findings, the studies using geldanamycin as an inhibitor of Hsp90 should be
      interpreted with caution.

PMID- 11983712
TI  - Congenital disorders of glycosylation type Ig is defined by a deficiency in
      dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase.
AB  - Type I congenital disorders of glycosylation (CDG I) are diseases presenting
      multisystemic lesions including central and peripheral nervous system deficits.
      The disease is characterized by under-glycosylated serum glycoproteins and is
      caused by mutations in genes encoding proteins involved in the stepwise assembly
      of dolichol-oligosaccharide used for protein N-glycosylation. We report that
      fibroblasts from a type I CDG patient, born of consanguineous parents, are
      deficient in their capacity to add the eighth mannose residue onto the lipid
      linked oligosaccharide precursor. We have characterized cDNA corresponding to the
      human ortholog of the yeast gene ALG12 that encodes the dolichyl-P
      Man:Man(7)GlcNAc(2)-PP-dolichyl alpha6-mannosyltransferase that is thought to
      accomplish this reaction, and we show that the patient is homozygous for a point
      mutation (T571G) that causes an amino acid substitution (F142V) in a conserved
      region of the protein. As the pathological phenotype of the fibroblasts of the
      patient was largely normalized upon transduction with the wild type gene, we
      demonstrate that the F142V substitution is the underlying cause of this new CDG,
      which we suggest be called CDG Ig. Finally, we show that the fibroblasts of the
      patient are capable of the direct transfer of Man(7)GlcNAc(2) from dolichol onto
      protein and that this N-linked structure can be glucosylated by UDP
      glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum.

PMID- 11983713
TI  - Binding to chaperones allows import of a purified mitochondrial precursor into
      mitochondria.
AB  - Refolding of the acid-unfolded precursor to mitochondrial aspartate
      aminotransferase (pmAAT) is inhibited when cytosolic Hsc70 is included in the
      refolding reaction (Artigues, A., Iriarte, A., and Martinez-Carrion, M. (1997) J.
      Biol. Chem. 272, 16852-16861). At low molar excess of Hsc70 pmAAT is recovered in
      insoluble aggregates containing equal amounts of Hsc70. However, in the presence
      of a large excess of Hsc70, refolding of pmAAT is still arrested, but the enzyme
      remains in solution. Similar behavior was observed with two other cytosolic
      chaperones, bovine Hsp90 and yeast Ydj1. Coimmunoprecipitation of pmAAT using
      Hsc70 antibodies confirmed the formation of soluble Hsc70-pmAAT complexes at high
      concentrations of the chaperone. Data from analytical centrifugation,
      sedimentation in glycerol gradients, and partial purification of the soluble
      complexes indicate that multiple Hsc70 molecules bind per pmAAT polypeptide
      chain. The absence of catalytic activity together with the protease
      susceptibility of pmAAT bound to Hsc70, Hsp90, or Ydj1 suggest that these
      chaperones bind and maintain pmAAT in a partially unfolded state, analogous to
      the import-competent conformation of the protein synthesized in cell-free
      extracts. Remarkably, the purified pmAAT bound to Hsc70 or Ydj1, but not to
      Hsp90, is imported by isolated mitochondria in a reticulocyte lysate-dependent
      manner. Thus, both Hsc70 and Ydj1 can trap an import-competent folding
      intermediate of pmAAT, but productive binding and import into mitochondria
      require the collaboration of additional cytosolic factors from the lysate.

PMID- 11983714
TI  - Models of growth hormone and IGF-1 deficiency: applications to studies of aging
      processes and life-span determination.
AB  - The remarkable progress in understanding the genetic basis of life-span
      determination in invertebrates indicates that impairments in the insulin-insulin
      like growth factor 1 (IGF-1) signaling cascade increase longevity. Similarities
      among insulin and IGF-1-like signaling pathways in invertebrates and mammals
      raise the possibility that modifications of these pathways may extend life span
      in mammals. Investigators using Ames, Snell, and growth hormone receptor knockout
      models have concluded that decreased growth hormone and IGF-1 are responsible for
      increased life span. In this review, we critique the dwarf models and, based on
      multiple endocrine deficiencies and developmental anomalies, conclude that these
      models may not be sufficient to assess the consequences of growth hormone or IGF
      1 deficiency on either biological aging or life span. We attempt to resolve some
      of these issues by presenting an alternative animal model of growth hormone-IGF-1
      deficiency. Finally, we propose an integrated explanation of growth hormone and
      IGF-1's contribution to the aging phenotype and life-span determination.

PMID- 11983715
TI  - Two-stage testing in microarray analysis: what is gained?
AB  - Microarray technology for gene expression studies offers powerful new technology
      for understanding changes in gene expression as a function of other observable or
      manipulable variables. However, microarrays also pose a number of new challenges.
      One of the most prominent of these is the difficulty in establishing a procedure
      for declaring whether a gene's expression level is associated with the
      independent variable that offers reasonable and specifiable false-positive (type
      1 error) and false-negative (type 2 error) rates. A recent article described a
      two-stage testing procedure to address these goals. However, information was not
      provided to indicate whether this procedure would or would not meet its
      objectives. Herein, we show mathematically that the two-stage procedure proposed
      does not provide benefits in terms of minimizing false-negatives while
      controlling the false-positive rate relative to standard single-stage testing.
      Therefore, investigators are encouraged to consider alternative analytic
      approaches.

PMID- 11983716
TI  - Physical performance and longevity in aged rats.
AB  - In humans, physical performance declines with increasing age, and in nondisabled
      older persons, scores on standardized performance measures, such as walking
      speed, repeated chair stands, and a balance test, predict the incidence of
      disability and reduced longevity. Here we show in aged rats (24-month-old Brown
      Norway x Fischer 344 male rats; n = 48) that conceptually similar performance
      measures, such as swimming speed and an inclined plane procedure, can be assessed
      longitudinally, and that over 6 months of follow-up from the age of 24 to 30
      months, performance declines progressively with increasing age. High baseline
      performance scores predict long-term longevity, a relationship that is also found
      in humans. The application of standardized physical performance measures to a
      variety of animal models of aging may help to define similarities between species
      in the underlying mechanisms of the age-related decline in performance,
      disability, and longevity.

PMID- 11983717
TI  - Effect of age on skeletal muscle proteolysis in extensor digitorum longus muscles
      of B6C3F1 mice.
AB  - The purpose of this study was to determine if age-related muscle atrophy is
      associated with an increased rate of protein degradation in extensor digitorum
      longus (EDL) muscles from young (YG; 2-4 months), middle-aged (MA; 12-17 months),
      and aged (AG; 22-24 months) B6C3F1 mice. EDL muscles from AG mice weighed less
      than EDL muscles from MA mice (p =.01). EDL muscles from MA mice weighed more
      than EDL muscles from YG mice (p =.02). The rate of protein degradation, as
      assessed by tyrosine release during in vitro incubations, was higher in EDL
      muscles from AG mice than it was in those from MA mice (p =.03). The rate of
      protein degradation was higher in EDL muscles from YG mice than it was in those
      from MA mice (p =.04). An inverse relationship existed between muscle mass and
      protein degradation (r = -.67; p =.0001). We conclude that skeletal muscle
      protein degradation rates decrease with maturation and increase with advancing
      age.

PMID- 11983718
TI  - Fertility and life span: late children enhance female longevity.
AB  - The relation between fertility and postmenopausal longevity is investigated for a
      sample of 1635 women from a historical (17th to 18th century) French-Canadian
      cohort who lived past the age of 50 years. We find that increased fertility is
      linked to increased rather than decreased postreproductive survival.
      Postreproductive life expectancy extension is found to be tied to late births.
      This finding sheds new light on the cost of reproduction and may be viewed as
      supporting a new paradigm that states that reproductive potential drives
      remaining longevity. The emerging reproductive potential concept complements the
      well-established cost of reproduction hypothesis. Alternative explanations for
      the observed association are also explored. A specific finding is that the degree
      to which mortality increases for 50-year-old mothers as a result of senescence is
      closely tied to the logarithm of the age of their youngest child. For example, 50
      year-old mothers experience a mortality decrease of 38% and an increase of
      remaining lifetime of 3.93 years for every 10-fold decrease in the age of their
      youngest child. This amount of gain in remaining life expectancy would apply to a
      mother with a two-year-old child as compared with a mother with a 20-year-old
      offspring. We also find evidence for the existence of vulnerable periods in human
      life history that are characterized by phases of heightened mortality and are
      found to be tied to reproduction and senescence.

PMID- 11983719
TI  - Exercise as the standard of care for elderly people.

PMID- 11983720
TI  - Exercise comes of age: rationale and recommendations for a geriatric exercise
      prescription.

PMID- 11983721
TI  - A conceptual framework of frailty: a review.
AB  - This article presents an overview of the increasingly common condition of
      frailty, which by and large lacks clarity of definition. A variety of sources
      provide this statement regarding definition, incidence, causation, rate, and time
      of appearance. Utilizing the newly elaborated process of symmorphosis, which
      explains the coadaptation of structure and function secondary to altered energy
      loads, I propose that frailty is a body-wide set of linked deteriorations
      including, but not confined to, musculoskeletal, cardiovascular, metabolic, and
      immunologic systems. The common final pathway that leads to this constellation of
      findings is usually keyed to a decline in physical activity either as a result of
      habit or disease inputs. As such, the state of frailty is largely separable from
      the process of aging and should thereby be susceptible to active intervention and
      reversal.

PMID- 11983722
TI  - Change in physical performance over time in older women: the Women's Health and
      Aging Study.
AB  - BACKGROUND: Although lower and upper extremity performance measures are widely
      used and represent validated physical function measures in older adults, there is
      limited information regarding the magnitude of changes in these measures over
      time. This study (i) assesses prospective changes in physical performance
      measures, (ii) defines a summary score that demonstrates a significant amount of
      change over time, and (iii) examines rates of decline according to age and
      baseline performance levels. METHODS: Data from the Women's Health and Aging
      Study (WHAS) were analyzed to assess change in the one third most disabled older
      women living in the community. Lower extremity function was assessed using
      walking speed, balance, and chair stands tests. The putting-on-blouse test, the
      lock and key test, the Purdue Pegboard test, and grip strength were used to gauge
      upper extremity function. Continuous and categorical summary performance scores
      were calculated using continuous and categorical data of lower and upper
      performance measures. RESULTS: After 3 years, lower extremity performance
      measures declined by 16%-27%, while upper extremity performance measures declined
      less (7%-24%). For lower extremity function, the continuous summary performance
      score showed a slightly greater 3-year decline from baseline (decline vs baseline
      mean: 23%; decline vs SD of the baseline mean: 59%) than the categorical score
      (22% and 41%, respectively). Older age and intermediate level of baseline
      performance were associated with the greatest decline, especially for lower
      extremity function. CONCLUSIONS: In moderately to severely disabled women aged 65
      or older, lower extremity measures show more change over 3 years than upper
      extremity measures. Among the lower extremity summary scores, the continuous
      score changes more over time than the categorical score with respect to the
      baseline SD. The lower extremity continuous summary performance score may be a
      useful outcome measure for clinical studies of physical performance in older
      women.

PMID- 11983723
TI  - Performance tests and disability: developing an objective index of mobility
      related limitation in older populations.
AB  - BACKGROUND: Disability reflects physiological limitations, social and
      environmental barriers, and "sickness" behavior. Being able to measure these
      influences separately would greatly assist interpretation of disability
      comparisons over time or between populations. This study aimed to identify an
      index of mobility-related limitations composed of physiological measures that are
      most closely associated with reported mobility disability in elders. METHODS:
      Data from the Third National Health and Nutrition Examination Survey (NHANES III)
      were used. Participants aged 60 and older were included in this analysis.
      Participants included 6596 respondents who were interviewed in their homes, and
      5724 (87%) of these attended a further examination. Domains of measurements
      included body measurements, bone densitometry, physical examination, spirometry,
      fundus photography, and physical performance measures. Multivariate models were
      developed on a random half subsample of the data and were validated on the other
      half. Receiver operating characteristic (ROC) areas and logit rank slopes were
      used to evaluate sets of measures. RESULTS: In weighted logistic regression
      models, six and five measures were significantly associated with difficulty and
      inability in walking a quarter of a mile, respectively. These mainly included
      measures of lower extremity and lung function. A relatively minimal loss of
      sensitivity and specificity occurred from using more economical models, employing
      a subset of the identified measures. CONCLUSIONS: Subsets of measures associated
      with reported mobility disability could provide objective indices of mobility
      related limitation for comparing populations or long-term population health
      monitoring.

PMID- 11983724
TI  - Influence of fat-free mass and functional status on resting energy expenditure in
      underweight elders.
AB  - BACKGROUND: In underweight elders, resting energy expenditure (REE) and its
      relationship with fat-free mass (FFM) could be modified by sarcopenia, physical
      activity, and functional limitation. The aims of this study were to investigate
      REE and its relationship with quantity and metabolic activity of FFM and to
      evaluate the influence of functional status on REE in underweight elderly
      subjects. METHODS: Forty-eight underweight elders (BMI < 20) and 54 normal weight
      elderly subjects (BMI 20-30) as a control group were selected. Body composition
      was determined by dual energy x-ray absorptiometry (DEXA). REE was measured by
      indirect calorimetry. Ability in activities of daily living (ADLs) was assessed
      by the Katz index. RESULTS: Underweight elders had significantly lower FFM, FFM
      index (FFM/height(2)), and REE than healthy subjects. REE adjusted for FFM with
      analysis of covariance remained significantly lower in the underweight group
      (1287 +/- 85 vs 1715 +/- 139 kcal/day in men, and 1124 +/- 63 vs 1366 +/- 91
      kcal/day in women). Katz index in the underweight group was inversely correlated
      with REE (r = -0.68; p <.001) even after removal of FFM, FM, and gender, by
      multiple regression analysis. In this model, FFM and Katz index together
      explained approximately 54% of REE variability. CONCLUSIONS: Underweight elderly
      subjects show a hypometabolism due to a reduction of both FFM quantity and its
      metabolic activity. Functional status in ADLs comes out as an important predictor
      of REE independently from FFM. The limited physical activity might be the
      underlying determinant of this hypometabolism, but further investigations are
      necessary to confirm this issue.

PMID- 11983725
TI  - Screening for depression in middle-aged and older puerto rican primary care
      patients.
AB  - BACKGROUND: Brief depression screens have recently been developed, but their use
      in older or minority populations has not been studied. To date, optimal
      depression screens and optimal cutpoints have not been identified for middle-aged
      and older Hispanic primary care patients. METHODS: This study compares multiple
      versions of four depression screening tools--Center for Epidemiologic Studies
      Depression Scale (CES-D), Geriatric Depression Scale, Yale 1-question screen, and
      PRIME-MD 2-question screen--to the Composite International Diagnostic Interview
      (CIDI), the World Health Organization's diagnostic interview, which has been
      validated in adult Latino populations, to assess convergent validity. Three
      hundred and three Puerto Rican primary care patients age 50 and older completed
      all screens and the CIDI in a face-to-face interview. Sensitivity and specificity
      for each screen were calculated, and receiver operator characteristic curves were
      generated. RESULTS: Between 34% and 61% of patients screened positive for
      depression, depending on the measure, with 12% meeting DSM-IV criteria for major
      depression (CIDI). The 10-item CES-D worked best to identify major depression in
      this population, with a sensitivity of 84% and specificity of 64% using a
      cutpoint of 3. CONCLUSIONS: The 10-item CES-D, which takes about 2 minutes to
      administer, is a useful tool for identifying Puerto Rican patients in need of an
      in-depth mental health evaluation in a primary care setting. A lower cutpoint of
      3 (instead of the conventional cutpoint of 4) is recommended for optimal
      sensitivity and specificity.

PMID- 11983726
TI  - Hypothyroidism in patients older than 55 years: an analysis of the etiology and
      assessment of the effectiveness of therapy.
AB  - BACKGROUND: Several epidemiological studies on the prevalence of hypothyroidism
      in the elderly have been reported; however, extensive series of elderly patients
      with thyroid dysfunction have not been studied. Our aim has been to assess the
      relative frequency of the diverse causes of hypothyroidism in a group of patients
      older than 55 years and the adequacy of control of thyroid function attained by
      levothyroxine therapy. METHODS: We performed a descriptive, observational, cross
      sectional study in the setting of a hospital endocrinology clinic. From a total
      of 1581 patients older than 55 who were complaining of a thyroid disorder, we
      studied a group of 655 patients with hypothyroidism. There were 559 women (85.3%,
      age 65.01 +/- 7.90 years) and 96 men (14.7%, 65.36 +/- 8.39 years). In every
      patient, we collected etiology, presence of goiter, time of evolution from
      diagnosis and from therapy prescription, previous and present treatments, current
      thyroid functional status (free thyroxine and thyrotropin concentration),
      adequacy of disease control, and thyroid autoimmune status. RESULTS: The causes
      of hypothyroidism were as follows: autoimmune thyroiditis, 308 (47.0%);
      postoperative hypothyroidism, 175 (26.7%); therapy for previous thyrotoxicosis,
      63 (9.6%); thyrotropin deficiency, 15 (2.3%); iodine excess, 6 (0.9%); subacute
      thyroiditis, 2 (0.3%); and unknown etiology, 86 (13.1%) patients. Most patients
      with autoimmune thyroiditis were positive for thyroid peroxidase antibodies at
      the time of the study (94.4%). Mean (+/- SD) age at diagnosis was 61.8 +/- 9.4
      years in men and 59.8 +/- 9.7 years in women. Median (range) duration of
      hypothyroidism was 1.4 (0-18) years in men and 3 (0-45) years in women ( p <.05).
      Adequacy of therapy was studied in 385 patients treated with replacement doses of
      levothyroxine. Two hundred and sixty (67.5%) of these subjects attained good
      control, whereas 125 (32.5%) showed inadequate control of the disease at the time
      of the study. A model of logistic regression showed that adequacy of therapy was
      dependent on the duration of therapy, but independent of age, gender, degree of
      hypothyroidism, etiology, autoimmune status, age at diagnosis, and dose of
      levothyroxine. A 2-year follow-up study performed in 56 newly diagnosed patients
      showed that an adequate control of hypothyroidism was attained in 35 (62.5%)
      patients at 6 months, in 46 (82.1%) patients at 1 year, and in 49 (87.5%) at 2
      years of therapy with levothyroxine. CONCLUSIONS: Autoimmune thyroiditis and
      postoperative hypothyroidism are the main causes of thyroid hypofunction in
      patients older than 55 years. The time from starting therapy is the main
      determinant of the adequacy of control of thyroid hypofunction in this
      population. With effective therapy and appropriate monitoring, more than 80% of
      the patients showed adequate control within 1 year of follow-up.

PMID- 11983727
TI  - Effects of transdermal testosterone on cognitive function and health perception
      in older men with low bioavailable testosterone levels.
AB  - BACKGROUND: Many men older than 50 years have bioavailable testosterone levels
      below the reference range for young adult men. The impact of the decreased
      androgen levels on cognition and health perception has received little attention.
      METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable
      testosterone levels below 128 ng/dl (lower limit for adult normal range) were
      randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo
      patches for 1 year. All men received 500 mg supplemental calcium and 400 IU
      vitamin D. Outcome measures included sex hormones [testosterone, bioavailable
      testosterone, sex hormone binding globulin (SHBG), estradiol, and estrone],
      cognitive tests (Digit Symbol, Digit Span, Trailmaking A and B), health
      perception (Medical Outcome Survey Short-form 36 or SF-36), lower extremity
      muscle strength and power, and calcium intake. RESULTS: Twenty-three men (34%)
      withdrew from the study; 44 men completed the trial. Bioavailable testosterone
      levels increased from 93 +/- 34 (SD) to 162 +/- 100 ng/dl (p <.002) at 12 months
      in the testosterone group (n = 24) while no change occurred in the control group
      (n = 20). While there was no change in estradiol levels in either group, estrone
      levels increased in the testosterone group (28 +/- 7 to 32 +/- 9 pg/dl, p =.017).
      Scores on the Digit Symbol test improved in both the testosterone and placebo
      groups. Scores on Trailmaking B improved in men treated with testosterone (p
      <.005), although the changes were not statistically different from the changes
      seen in the placebo group. Twelve-month scores on Trailmaking B for the entire
      group were correlated with 12-month testosterone levels (p =.016). Scores for
      health perception measured by SF-36 did not change significantly, though scores
      of mental and general health declined in both groups during the 12-month
      intervention. Twelve-month bioavailable testosterone scores were directly
      correlated with scores for physical role (p =.022), vitality (p =.036), and the
      physical composite score (p =.010). CONCLUSIONS: Transdermal testosterone
      treatment in men with low bioavailable testosterone levels does not impair and
      may improve cognitive function. Treatment did not improve health perception but
      this may have been due to the side effects of skin irritation suggested by
      similar reactions in both the testosterone and placebo groups.

PMID- 11983728
TI  - Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass
      and muscle strength in elderly men and women: the Health ABC Study.
AB  - BACKGROUND: A decline in muscle mass and muscle strength characterizes normal
      aging. As clinical and animal studies show a relationship between higher cytokine
      levels and low muscle mass, the aim of this study was to investigate whether
      markers of inflammation are associated with muscle mass and strength in well
      functioning elderly persons. METHODS: We used baseline data (1997-1998) of the
      Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white
      men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed
      tomography), appendicular muscle mass (dual-energy x-ray absorptiometry),
      isokinetic knee extensor strength (KinCom), and isometric grip strength were
      measured. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha
      (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Higher cytokine levels were generally associated with lower muscle mass and lower
      muscle strength. The most consistent relationship across the gender and race
      groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip
      strength was 1.1 to 2.4 kg lower (p <.05) after adjustment for age, clinic site,
      health status, medications, physical activity, smoking, height, and body fat. An
      overall measure of elevated cytokine level was created by combining the levels of
      IL-6 and TNF-alpha. With the exception of white men, elderly persons having high
      levels of IL-6 (>1.80 pg/ml) as well as high levels of TNF-alpha (>3.20 pg/ml)
      had a smaller muscle area, less appendicular muscle mass, a lower knee extensor
      strength, and a lower grip strength compared to those with low levels of both
      cytokines. CONCLUSIONS: Higher plasma concentrations of IL-6 and TNF-alpha are
      associated with lower muscle mass and lower muscle strength in well-functioning
      older men and women. Higher cytokine levels, as often observed in healthy older
      persons, may contribute to the loss of muscle mass and strength that accompanies
      aging.

PMID- 11983729
TI  - Incidence of new atherothrombotic brain infarction in older persons with prior
      myocardial infarction and serum low-density lipoprotein cholesterol >or=125 mg/dl
      treated with statins versus no lipid-lowering drug.
AB  - BACKGROUND: We report the incidence of new atherothrombotic brain infarction
      (ABI) in older men and women with prior myocardial infarction and a serum low
      density lipoprotein (LDL) cholesterol of >or=125 mg/dl treated with statins and
      with no lipid-lowering drug. METHODS: The incidence of new ABI was investigated
      in an observational prospective study of 1410 men and women, mean age 81 +/- 9
      years, with prior myocardial infarction and a serum LDL cholesterol of >or=125
      mg/dl treated with statins (679 persons or 48%) and with no lipid-lowering drug
      (731 persons or 52%). Follow-up was 36 +/- 21 months. RESULTS: At follow-up, the
      stepwise Cox regression model showed that significant independent predictors of
      new ABI were age (risk ratio = 1.04 for a 1-year increase in age), cigarette
      smoking (risk ratio = 3.5), hypertension (risk ratio = 3.1), diabetes mellitus
      (risk ratio = 2.3), initial serum LDL cholesterol (risk ratio = 1.01 for each 1
      mg/dl increase), initial serum high-density lipoprotein cholesterol (risk ratio =
      0.97 for each 1 mg/dl increase), prior stroke (risk ratio = 2.5), and use of
      statins (risk ratio = 0.40). The Cochran-Armitage test showed a trend in the
      reduction of new ABI in persons treated with statins as the level of serum LDL
      cholesterol decreased ( p <.0001). CONCLUSIONS: Use of statins caused a 60%,
      significant, independent reduction in new ABI in older men and women with prior
      myocardial infarction and a serum LDL cholesterol of >or=125 mg/dl.

PMID- 11983730
TI  - Caregiving as a dyadic process: perspectives from caregiver and receiver.
AB  - Most family caregiving research has relied on the perspective of the caregiver
      but has not systematically examined the views and opinions of the elder who is
      receiving care. The present study examined 63 caregiving dyads to determine how
      the responses of each member had an impact on the well-being of the other member
      of the dyad. Caregiver relationship strain predicted his or her own depression
      and negative health, but no significant association was found between caregiver
      and care recipient outcomes. Multilevel modeling was used to assess the level of
      dyadic discrepancy over the care recipient's needs and appraisal of caregiving
      difficulties. Results indicate that there is little disagreement over the care
      recipient's needs, but a significant amount of variation in how much the care
      recipient and caregiver agree on their appraisals of caregiving difficulties.
      Relationship strain perceived by the caregiver, but not the care recipient, was
      significantly associated with this disagreement.

PMID- 11983731
TI  - Coping and depression in Alzheimer's caregivers: longitudinal evidence of
      stability.
AB  - The present study examined the longitudinal relationship between depressive
      symptoms and coping strategies in older adult primary caregivers of
      noninstitutionalized Alzheimer's patients. Coping and depression were measured in
      51 healthy, nondepressed caregivers (37 women, 14 men) at 4 times of testing
      approximately 6 months apart. The caregivers' coping strategies and depressive
      symptoms were found to be largely stable over all times of testing-with a
      recently developed method for evaluating construct stability-despite significant
      decline in the patients' cognitive functioning over the same interval. Avoidance
      coping was also found to be positively associated with depressive symptoms.
      Results suggest that a strong stable component is present in caregiver coping
      style and that caregiver intervention researchers may want to examine the extent
      to which commonly used outcome measures are assessing stable caregiver traits
      rather than state-dependent distress.

PMID- 11983732
TI  - Retirement transitions, gender, and psychological well-being: a life-course,
      ecological model.
AB  - This longitudinal study investigated the relationship between retirement
      transitions and subsequent psychological well-being using data on 458 married men
      and women (aged 50-72 years) who were either still in their primary career jobs,
      retired, or had just made the transition to retirement over the preceding 2
      years. The findings show that the relationship between retirement and
      psychological well-being must be viewed in a temporal, life course context.
      Specifically, making the transition to retirement within the last 2 years is
      associated with higher levels of morale for men, whereas being "continuously"
      retired is related to greater depressive symptoms among men. The results suggest
      the importance of examining various resources and contexts surrounding retirement
      transitions (gender, prior level of psychological well-being, spouses'
      circumstance, and changes in personal control, marital quality, subjective
      health, and income adequacy) to understand the dynamics of the retirement
      transition and its relationship with psychological well-being.

PMID- 11983733
TI  - Inhibitory changes after age 60 and their relationship to measures of attention
      and memory.
AB  - This study examined the relationship between age and inhibitory functioning
      within a sample of older adults ranging in age from 60 to 85 years old. On the
      basis of earlier research, and confirmed by factor analysis, measures typically
      referred to as frontal lobe tasks were used as measures of inhibitory
      functioning. Findings demonstrated that inhibitory processes continued to decline
      with advancing age within the older sample. In addition, the role of inhibition
      in age-related performance deficits on a verbal list learning measure and an
      attention measure was examined. Hierarchical regression analyses showed that
      inhibition accounted for a significant proportion of the age-related variance on
      the two cognitive measures, whereas measures of reading speed accounted for a
      smaller proportion of the variance. In addition, when inhibition was first
      covaried out, reading speed no longer accounted for a significant proportion of
      the age-related variance. It is argued that inhibition is an important
      contributor to age-related performance decrements in cognition.

PMID- 11983734
TI  - Word frequency effects in priming performance in young and older adults.
AB  - The present study examined word frequency effects on implicit priming in older
      adults compared with younger adults. In Experiment 1 participants performed a
      spelling test consisting of primed and unprimed homophones (e.g., mourning) and
      nonhomophones (e.g., militant). Older adults spelled more unprimed, low-frequency
      homophones than did younger adults, suggesting that there are age-related
      differences in base-rate spelling of lower frequency homophones. Experiment 2
      involved a word-fragment completion task that primed both high- and low-frequency
      words. Young adults showed larger priming effects for low-frequency words,
      whereas older adults showed smaller and similar priming effects for high- and low
      frequency words. Experiment 3 replicated the finding that word frequency has no
      effect on priming performance in older adults on a word-fragment completion task.
      These studies found differential word frequency effects on priming performance
      between young and older adults.

PMID- 11983735
TI  - Aging and bilateral symmetry detection.
AB  - The salience of bilateral symmetry varies as a function of the orientation of the
      symmetry axis. Vertical symmetry is most salient, followed by horizontal and then
      oblique orientations. We tested symmetry detection in different age groups to
      determine whether performance of this intermediate-level visual task is affected
      by normal, nonpathological aging. We tested forty participants and analyzed the
      results with respect to age group and symmetry orientation (vertical, horizontal,
      and 45 degree oblique). There was a vertical symmetry detection advantage for all
      participants, where sensitivity was highest for vertical symmetry, followed by
      horizontal symmetry, and then the oblique symmetry. Sensitivity to symmetry did
      not differ for the two younger age groups (aged 19-39 and 40-60), but declined
      significantly for the group aged 61-70, and declined again for the oldest group
      aged 71-80. This age-related difference in sensitivity to symmetry was not
      reflected in a measure of bias, where there were no differences as a function of
      age.

PMID- 11983736
TI  - Anxiety, cognitive performance, and cognitive decline in normal aging.
AB  - A sample of 704 cognitively intact individuals (M age = 63.7 years) performed a
      battery of cognitive tests on as many as three occasions, at approximately 3-year
      intervals. The authors used random effects models to analyze cross-sectional
      relationships between cognitive performance and state anxiety and longitudinal
      relationships between cognitive change and neuroticism, after controlling for
      gender, age, and education. Cross-sectionally, higher state anxiety was
      associated with poorer performance on Wechsler Adult Intelligence Scale Synonyms,
      WIT III Analogies, Koh's Block Design, two measures of visual learning (Names and
      Faces and Thurstone's Picture Memory), and, for men, CVB-Scales Digit Span Test
      and Card Rotations. In longitudinal models, the main effects for neuroticism were
      significant for Block Design, Symbol Digit, and Names and Faces, but there were
      no significant interactions among neuroticism, gender, and time. These results
      provide some support for Eysenck's processing efficiency theory but none for
      neuroticism as a risk factor for cognitive decline in normal aging.

PMID- 11983737
TI  - Age excuses: conversational management of memory failures in older adults.
AB  - The social consequences of appealing to age to excuse memory failure were
      examined in 2 vignette-based studies. In Study 1, 75 older (M = 72 years) and 78
      young (M = 22 years) adults evaluated forgetful older targets in their 70s who
      used their age, lack of ability, lack of effort, or the situation to explain
      forgetting. In Study 2, 105 older (M = 72 years) and 105 young participants (M =
      19 years) evaluated forgetful targets with no specific age given in 4 excuse
      conditions (age, ability, situation, and no excuse). In support of the prediction
      of positive consequences, age excuses were rated as more believable than
      situation in both studies and more believable and socially fluent than effort in
      Study 1. In support of predictions of negative consequences, both groups in Study
      2 rated target persons who used an age excuse to be much older than their peers
      and, along with ability excuse users, as eliciting more worry and frustration
      than the others. Moreover, young adults showed additional sensitivity to the
      negative aspects of age excuses in terms of worry and frustration in Study 1 and
      anticipated repeat forgetting in Study 2. These results suggest that although age
      excuses may relieve socially awkward situations, this strategy reinforces
      negative age stereotyping of the older forgetter.

PMID- 11983738
TI  - Terminal decline and markers of cerebro- and cardiovascular disease: findings
      from a longitudinal study of the oldest old.
AB  - The purpose of this study was to examine the cognition-survival relationship
      among nondemented individuals in late life. The longitudinal design included
      three examinations at 2-year intervals. At baseline, 466 individuals (age range =
      80-98) were examined. During the 6 years of follow-up, 206 individuals died. Four
      survival groups were defined on the basis of mortality prior to the subsequent
      measurement occasion. Tests of cognitive functioning encompassed the domains of
      crystallized knowledge, inductive reasoning, visuospatial ability, short-term
      memory, episodic memory, and speed. Significant associations were found between
      cognitive performance at baseline and subsequent survival. After adjusting for
      stroke and markers of cardiovascular disease, the authors found that only three
      out of six cognitive domains remained significant predictors of survival. The
      longitudinal analyses revealed limited evidence for an accelerated decline prior
      to death. The main results suggest that level of cognitive performance in late
      life is associated with proximity to death, that this relationship is
      longstanding, and that it is partially influenced by compromised cardio- and
      cerebrovascular functioning.

PMID- 11983739
TI  - Age, skill transfer, and conjunction search.
AB  - Ten younger and ten older adults were provided with 16 sessions of conjunction
      search under consistent mapping, where target and distractors remain constant in
      identity. The target and one distractor were reversed after every fourth session.
      After the first four training sessions, on target-present trials, display size
      slopes were near zero for both age groups. However, on target-absent trials,
      older adults continued to show significantly larger display size effects than
      younger adults. There were no systematic age differences in either the
      probability of fixating objects that possess the target's features or in the
      amount of disruption at any reversal. Thus, although older adults exhibited more
      conservative criteria in visual search, they developed proficient and flexible
      search skill to the same degree as their younger counterparts. These data have
      implications for models of visual attention, skill acquisition, and cognitive
      aging.

PMID- 11983740
TI  - Risk and protective factors for physical functioning in older adults with and
      without chronic conditions: MacArthur Studies of Successful Aging.
AB  - OBJECTIVES: Older age continues to be seen as a period of declining health and
      functioning. The inevitability of declines, however, may be exaggerated,
      including declines for those with chronic health conditions. METHODS: Data from
      the MacArthur Study of Successful Aging were used to examine the impact of
      sociodemographic, health status, health behavior, and social and psychological
      factors on patterns of change in physical functioning over a 2.5-year interval
      for groups of older adults reporting prevalent hypertension, diabetes,
      cardiovascular disease, cancer, or fractures, and those reporting no chronic
      conditions at baseline. RESULTS: Findings from multiple regression analyses
      revealed a consistently protective effect of regular physical activity with
      respect to patterns of change in physical functioning in nearly all groups. For
      those with cardiovascular disease, greater emotional support was associated with
      higher baseline levels and less declines in functioning, whereas greater social
      conflict was associated with greater decline among those with hypertension or
      diabetes. For those with a history of cancer, instrumental self-efficacy beliefs
      were protective, whereas lower psychological symptomatology was associated with
      less risk of decline among those with a history of fracture. Social and
      psychological factors were unrelated to changes in functioning for those with no
      chronic conditions. DISCUSSION: These findings suggest that risks for decline in
      physical functioning are influenced by a number of potentially modifiable factors
      that could be targets for interventions to promote better functioning, even among
      older adults with various types of chronic conditions.

PMID- 11983741
TI  - Living arrangements of older adults in the developing world: an analysis of
      demographic and health survey household surveys.
AB  - OBJECTIVES: This study examines living arrangements of older adults across 43
      developing countries and compares patterns by gender, world regions, and macro
      level indicators of socioeconomic development. METHODS: Data are from Demographic
      and Health Surveys. The country is the unit of analysis. Indicators include
      household size, headship, relationship to head, and coresidence with spouse,
      children, and others. Unweighted regional averages and ordinary least-squares
      regressions determine whether variations exist. RESULTS: Average household sizes
      are large, but a substantially greater proportion of older adults live alone than
      do individuals in other age groups. Females are more likely than males to live
      alone and are less likely to live with a spouse or head of a household. Heading a
      household and living in a large household and with young children is more
      prevalent in Africa than elsewhere. Coresidence with adult children is most
      common in Asia and least in Africa. Coresidence is more frequent with sons than
      with daughters in both Asia and Africa, but not in Latin America. As a country's
      level of schooling rises, most living arrangement indicators change with families
      becoming more nuclear. Urbanization and gross national product have no
      significant effects. DISCUSSION: Although living arrangements differ across world
      regions and genders, within-region variations exist and are explained in part by
      associations between countrywide levels of education and household structure.
      These associations may be caused by a variety of intermediating factors, such as
      migration of children and preferences for privacy.

PMID- 11983742
TI  - Neighbors, friends, and other nonkin caregivers of community-living dependent
      elders.
AB  - OBJECTIVES: To describe naturally occurring care relationships between unpaid,
      nonprofessional, nonkin (unrelated) caregivers and frail community-living older
      adults. METHODS: Face-to-face, semistructured interviews were conducted with a
      convenience sample of 114 caregivers and care recipients recruited from the
      community through a variety of organizations. Standard techniques for thematic
      analysis of qualitative data were used along with descriptive and other
      statistics as appropriate for numerate data. RESULTS: Nonkin caregiving proved to
      be heterogeneous in initiation of relationship, form, duration, tasks performed,
      and association with family caregivers. Partnerships ranged from 0.1 to 57 years
      in duration, with just over half (58%) starting with the provision of care. Many
      caregivers (47%) were themselves older adults, aged 65 or older. There was little
      variation in what motivated or rewarded caregivers, many of whom felt morally
      obligated to help. More than half the sample used kin terms to characterize their
      relationship. Four distinct styles of relationship were discerned, varying by
      degree of emotional intimacy and types of assistance given. All relationships,
      however, involved socializing and help with at least two instrumental tasks of
      daily life. DISCUSSION: This kind of caregiving is important for sustaining
      community living for about 10% of frail elderly persons. A greater understanding
      is needed, from both theoretical and practical perspectives, of when and how
      nonkin relationships are beneficial and why they in many ways successfully mirror
      the actions and sentiments of family caregivers.

PMID- 11983743
TI  - Gender and health: a study of older unlike-sex twins.
AB  - OBJECTIVES: The primary goal of this study was to assess gender differences in
      various measures of health conditions, symptoms, and self-rated health among
      older persons by comparing brothers and sisters in a sample of unlike-sex twins.
      METHODS: All living pairs of unlike-sex twins born between 1906 and 1925 were
      identified through the Swedish Twin Registry and sent surveys assessing health
      and other factors. This population-based sample consisted of 605 twin pairs.
      Paired sample t tests were used to analyze gender differences in health-related
      measures, including a three-level measure of health problems based on physicians'
      ratings. RESULTS: Women had more total health conditions, not life-threatening
      health conditions, somewhat life-threatening cardiovascular conditions, and
      physical and psychological symptoms. Men had more very life-threatening health
      conditions and cardiovascular conditions. No gender differences were found in
      somewhat life-threatening health conditions, total cardiovascular conditions, or
      self-rated health. DISCUSSION: Important gender differences and similarities in
      health were found using an unlike-sex twin design that reduced variability due to
      background characteristics. This design also minimized problems caused by gender
      differences in survival. Research on gender and health in older persons requires
      more detailed approaches to address the complexity of this topic.

PMID- 11983744
TI  - Informal caregiving for diabetes and diabetic complications among elderly
      americans.
AB  - OBJECTIVES: Little is known regarding the amount of time spent by unpaid
      caregivers providing help to elderly individuals for disabilities associated with
      diabetes mellitus (DM). We sought to obtain nationally representative estimates
      of the time, and associated cost, of informal caregiving provided to elderly
      individuals with diabetes, and to determine the complications of DM that
      contribute most significantly to the subsequent need for informal care. METHODS:
      We estimated multivariable regression models using data from the 1993 Asset and
      Health Dynamics Among the Oldest Old Study, a nationally representative survey of
      people aged 70 or older (N = 7,443), to determine the weekly hours of informal
      caregiving and imputed cost of caregiver time for community-dwelling elderly
      individuals with and without a diagnosis of DM. RESULTS: Those without DM
      received an average of 6.1 hr per week of informal care, those with DM taking no
      medications received 10.5 hr, those with DM taking oral medications received 10.1
      hr, and those with DM taking insulin received 14.4 hr of care (p <.01).
      Disabilities related to heart disease, stroke, and visual impairment were
      important predictors of diabetes-related informal care. The total cost of
      informal caregiving for elderly individuals with diabetes in the United States
      was between $3 and $6 billion per year, similar to previous estimates of the
      annual paid long-term care costs attributable to DM. DISCUSSION: Diabetes imposes
      a substantial burden on elderly individuals, their families, and society, both
      through increased rates of disability and the significant time that informal
      caregivers must spend helping address the associated functional limitations.
      Future evaluations of the costs of diabetes, and the cost-effectiveness of
      diabetes interventions, should consider the significant informal caregiving costs
      associated with the disease.

PMID- 11983745
TI  - Do elderly Medicare recipients contact physicians appropriately?
AB  - OBJECTIVES: This research identified characteristics of persons and their illness
      episodes that predict appropriate and inappropriate decisions to seek medical
      care. METHODS: This study analyzes 1,292 health care decisions of 885 elderly
      members of an HMO in Los Angeles. Illness episodes are divided into three
      categories based on the expertise of a panel of 22 geriatricians, using a formal
      mathematical analysis derived from anthropological consensus theory. These
      categories are physician visit not recommended, physician visit recommended, and
      physician visit mandatory. Physician contact is regressed on a list of variables
      derived from Andersen's behavioral model separately for each group of episodes.
      RESULTS: Although the variables indicating perceived seriousness and duration of
      the episode consistently predict the decision to contact a physician, regardless
      of whether that contact is considered appropriate by the geriatrician panel, the
      variables indicating other illness responses and predisposing personal attributes
      have less consistent patterns of significance. DISCUSSION: The category of
      episodes (visit recommended) for which predisposing personal attributes figure
      most strongly in the treatment decision is the one for which there are no clear
      cultural directives to action. Implications for health education and policy are
      drawn from the findings.

PMID- 11983746
TI  - The influence of menstrual cycle phase on surgical treatment of primary breast
      cancer: have we made any progress over the past 13 years?

PMID- 11983748
TI  - White House report on alternative medicine draws criticism.

PMID- 11983751
TI  - Tests of three herbal therapies yield disappointing results.

PMID- 11983752
TI  - Cardiotoxicity concerns prompt data review in breast cancer trial.

PMID- 11983753
TI  - Adherence to therapy with oral antineoplastic agents.
AB  - With the rise in availability and increasing use of oral anticancer agents,
      concerns about adherence to prescribed regimens will become an increasingly
      important issue in oncology. Few published studies have focused on adherence to
      oral antineoplastic therapy, in part because the vast majority of chemotherapy is
      delivered intravenously in physicians' offices or hospitals. In this article, we
      review current knowledge of adherence behavior with regard to oral medications in
      general, including factors associated with adherence and methods for measuring
      adherence. We also review published studies of adherence to oral antineoplastic
      agents in adult and pediatric populations and adherence issues in cancer
      prevention. The available evidence reveals that patient adherence to oral
      chemotherapy recommendations is variable and not easily predicted. Adherence
      rates ranging from less than 20% to 100% have been reported, and certain
      populations, such as adolescents, pose particular challenges. Future efforts
      should focus on improving measurement and prediction of adherence and on
      developing interventions to improve adherence for both patients in clinical
      trials and patients being treated outside of the research setting. Assessment of
      adherence among individuals with cancer and implementation of interventions in
      situations of poor adherence should improve clinical outcomes.

PMID- 11983754
TI  - Mastectomy and oophorectomy by menstrual cycle phase in women with operable
      breast cancer.
AB  - BACKGROUND: It is unclear whether the phase of the menstrual cycle in which
      primary surgical treatment occurs influences disease-free survival (DFS) and
      overall survival (OS) in premenopausal women with breast cancer. We investigated
      this question in the context of a clinical trial comparing mastectomy alone with
      mastectomy plus adjuvant oophorectomy and tamoxifen in premenopausal women with
      operable breast cancer. METHODS: The date of the first day of the last menstrual
      period (LMP) was used to estimate the phase of the menstrual cycle when the
      surgeries were done. Follicular phase was defined as day 1-14 from LMP. Luteal
      phase was defined as day 15-42 from LMP. DFS and OS statistics were determined
      and analyzed by Cox proportional hazards ratios and Kaplan-Meier methods. All
      statistical tests were two-sided. RESULTS: We analyzed results for 565 women who
      reported an LMP within 42 days before surgery. For women in the mastectomy only
      arm (n = 289), there were no differences in DFS or OS by menstrual cycle phase.
      For women in the adjuvant treatment arm (n = 276), those whose surgery occurred
      during the luteal phase (n = 158) had better DFS (relative risk [RR] = 0.54; 95%
      confidence interval [CI] = 0.32 to 0.96; P =.02) and OS (RR = 0.53; 95% CI = 0.30
      to 0.95; P =.03) than those whose surgery occurred during the follicular phase (n
      = 118). Moreover, women whose surgery occurred during the luteal phase and who
      received adjuvant therapy had better 5-year DFS than did women whose surgery
      occurred during the follicular phase (84%; 95% CI = 78% to 90% versus 67%; 95% CI
      = 58% to 78%; P =.02); they also had better OS (85%; 95% CI = 78% to 92% versus
      75%; 95% CI = 66% to 84%; P =.03). CONCLUSIONS: The phase of the menstrual cycle
      at which surgery was done had no impact on survival for women who received
      mastectomy only. However, women who received a mastectomy and surgical
      oophorectomy and tamoxifen during the luteal phase had better outcomes than women
      who received surgery during the follicular phase.

PMID- 11983755
TI  - A randomized controlled trial of interventions to promote cervical cancer
      screening among Chinese women in North America.
AB  - BACKGROUND: North American Chinese women have lower levels of Papanicolaou (Pap)
      testing than other population subgroups. We conducted a randomized controlled
      trial to evaluate the effectiveness of two alternative cervical cancer screening
      interventions for Chinese women living in North America. METHODS: Four hundred
      and eighty-two Pap testing underutilizers were identified from community-based
      surveys of Chinese women conducted in Seattle, Washington, and Vancouver, British
      Columbia. These women were randomly assigned to one of two experimental arms or
      control status. Several Chinese-language materials were used in both experimental
      arms: an education-entertainment video, a motivational pamphlet, an educational
      brochure, and a fact sheet. Women in the first experimental group (outreach
      worker intervention) received the materials, as well as tailored counseling and
      logistic assistance, during home visits by trilingual, bicultural outreach
      workers. Those in the second experimental group (direct mail intervention)
      received the materials by mail. The control group received usual care. Follow-up
      surveys were completed 6 months after randomization to ascertain participants'
      Pap testing behavior. All statistical tests were two-sided. RESULTS: A total of
      402 women responded to the follow-up survey (83% response rate). Of these women,
      50 (39%) of the 129 women in the outreach group, 35 (25%) of the 139 women in the
      direct mail group, and 20 (15%) of the 134 women in the control group reported
      Pap testing in the interval between randomization and follow-up data collection
      (P<.001 for outreach worker versus control, P =.03 for direct mail versus
      control, and P =.02 for outreach worker versus direct mail). Intervention effects
      were greater in Vancouver than in Seattle. CONCLUSION: Culturally and
      linguistically appropriate interventions may improve Pap testing levels among
      Chinese women in North America.

PMID- 11983756
TI  - Hematopoietic and lymphatic cancers in relatives of patients with infectious
      mononucleosis.
AB  - BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related
      infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is
      detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in
      young adult patients, it is detected at a relatively low frequency in these
      cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with
      high social class, and unknown confounding factors that are also associated with
      socioeconomic status might explain or contribute to the apparent association
      between these diseases. To indirectly assess the importance of socioeconomic
      status on the association between these diseases, we determined the risk for
      hematopoietic and lymphatic cancers in first-degree relatives of patients with
      confirmed EBV-related infectious mononucleosis. METHODS: We identified parents,
      siblings, and offspring of 17,045 persons with serologically confirmed EBV
      related infectious mononucleosis. Subjects in these cohorts were linked with the
      population-based Danish Cancer Register to identify those developing
      hematopoietic/lymphatic cancers after the index patient was diagnosed with
      infectious mononucleosis. The relative risk for cancer in the infectious
      mononucleosis family members was expressed as standardized incidence ratios
      (SIRs; i.e., the ratio between the number of cancers observed and the number of
      cancers expected, obtained from age-specific, sex-specific, and period-specific
      incidence rates). RESULTS: We identified 8052 parents, 5264 siblings, and 28,605
      offspring of patients with EBV-related infectious mononucleosis who were followed
      for a total of 892,213 person-years at risk. The risk for Hodgkin's lymphoma was
      unaltered in the combined group of first-degree relatives of these patients (SIR
      = 0.99; 95% confidence interval [95% CI] = 0.62 to 1.59; number of cases [n] =
      17), in the group of parents (SIR = 0.83; 95% CI = 0.31 to 2.22; n = 4), in the
      group of siblings (SIR = 0.96; 95% CI = 0.31 to 2.97; n = 3), and in the group of
      offspring (SIR = 1.08; 95% CI = 0.58 to 2.02; n = 10). CONCLUSION: The
      unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV
      related infectious mononucleosis indicates that socioeconomic confounding is an
      unlikely explanation for the association between EBV-related infectious
      mononucleosis and Hodgkin's lymphoma.

PMID- 11983757
TI  - p53 Genotypes and Haplotypes Associated With Lung Cancer Susceptibility and
      Ethnicity.
AB  - BACKGROUND: The p53 tumor suppressor protein is important in cell-cycle control,
      apoptosis, and DNA repair. Mutations in p53 have been associated with inherited
      cancer susceptibility. Because there is a difference in the risk of lung cancer
      among different ethnic groups, we examined associations between ethnicity and
      three polymorphisms in p53 (one exonic and two intronic) and haplotypes for the
      three loci and risk of lung cancer. We also examined the functionality of the p53
      variants in apoptosis and DNA repair. METHODS: In a case-control study, we
      frequency matched (by age, sex, and ethnicity) 635 lung cancer case patients and
      635 control subjects. p53 genotypes and haplotypes at the three polymorphic sites
      were determined by restriction fragment length polymorphism analysis of
      lymphocyte DNA. Odds ratios (ORs) and 95% confidence intervals (CIs) for the
      association between genotype or haplotype and lung cancer risk were determined by
      logistic regression analysis. Apoptosis and DNA repair capacity were measured in
      22 lymphoblastoid cell lines to determine the functional effects of the
      polymorphisms. All statistical tests were two-sided. RESULTS: Genotype and
      haplotype frequency distributions were strongly dependent on ethnicity; variant
      allele frequencies were highest in African-Americans (29.1%) and lowest in
      Mexican-Americans (12.2%). Each of the three polymorphisms was associated with an
      increased risk of lung cancer among all ethnic groups. Moreover, for all three
      polymorphisms, increased variant allele copy number was associated with increased
      risk of lung cancer. Similarly, the variant haplotypes were also associated with
      an increased risk for lung cancer. Lymphoblastoid cell lines with all wild-type
      alleles at the three loci had statistically significantly higher apoptotic
      indices (13.66%, 95% CI = 8.61% to 18.71%) and DNA repair capacity (27.63%, 95%
      CI = 21.72% to 33.53%) than cell lines with at least one variant allele at all
      three loci (3.50%, 95% CI = 1.08% to 5.91%; and 17.48%, 95% CI = 7.99% to 26.96%,
      respectively). CONCLUSIONS: p53 polymorphisms may be associated with increased
      lung cancer risk and may affect p53 function.

PMID- 11983758
TI  - Host circadian clock as a control point in tumor progression.
AB  - BACKGROUND: The circadian timing system controlled by the suprachiasmatic nuclei
      (SCN) of the hypothalamus regulates daily rhythms of motor activity and
      adrenocortical secretion. An alteration in these rhythms is associated with poor
      survival of patients with metastatic colorectal or breast cancer. We developed a
      mouse model to investigate the consequences of severe circadian dysfunction upon
      tumor growth. METHODS: The SCN of mice were destroyed by bilateral electrolytic
      lesions, and body activity and body temperature were recorded with a radio
      transmitter implanted into the peritoneal cavity. Plasma corticosterone levels
      and circulating lymphocyte counts were measured (n = 75 with SCN lesions, n = 64
      sham-operated). Complete SCN destruction was ascertained postmortem. Mice were
      inoculated with implants of Glasgow osteosarcoma (n = 16 with SCN lesions, n = 12
      sham-operated) or pancreatic adenocarcinoma (n = 13 with SCN lesions, n = 13 sham
      operated) tumors to determine the effects of altered circadian rhythms on tumor
      progression. Time series for body temperature and rest-activity patterns were
      analyzed by spectral analysis and cosinor analysis. Parametric data were compared
      by the use of analysis of variance (ANOVA) and survival curves with the log-rank
      test. All statistical tests were two-sided. RESULTS: The 24-hour rest-activity
      cycle was ablated and the daily rhythms of serum corticosterone level and
      lymphocyte count were markedly altered in 75 mice with complete SCN destruction
      as compared with 64 sham-operated mice (two-way ANOVA for corticosterone:
      sampling time effect P<.001, lesion effect P =.001, and time x lesion interaction
      P<.001; for lymphocytes P =.001,.002, and.002 respectively). Body temperature
      rhythm was suppressed in 60 of the 75 mice with SCN lesions (P<.001). Both types
      of tumors grew two to three times faster in mice with SCN lesions than in sham
      operated mice (two-way ANOVA: P<.001 for lesion and for tumor effects; P =.21 for
      lesion x tumor effect interaction). Survival of mice with SCN lesions was
      statistically significantly shorter compared with that of sham-operated mice (log
      rank P =.0062). CONCLUSIONS: Disruption of circadian rhythms in mice was
      associated with accelerated growth of malignant tumors of two types, suggesting
      that the host circadian clock may play an important role in endogenous control of
      tumor progression.

PMID- 11983759
TI  - Safety of homeopathic products.

PMID- 11983760
TI  - Waiting in the NHS: part 1--a diagnosis.

PMID- 11983761
TI  - The hypocretin/orexin system.

PMID- 11983762
TI  - Mechanisms underlying nystagmus.

PMID- 11983763
TI  - Medical treatment of nystagmus and its visual consequences.

PMID- 11983764
TI  - Surgical management of nystagmus.

PMID- 11983765
TI  - Dementia and ethics: the views of informal carers.
AB  - There has been little work on the ethical issues facing non-professionals who
      care for relatives or others with dementia. A qualitative pilot study was
      conducted in ten such individuals, eight of them women, caring for persons drawn
      mainly from one general practice. The interviews indicated that many of the
      dilemmas faced by carers are ethical and that the issues differ from those faced
      by professionals. Ethical issues are sometimes the most troublesome matter for
      carers. Unlike issues for professionals, they arise from a personal context and
      are shaped by long-term relationships.

PMID- 11983766
TI  - Suspected testicular torsion: a survey of clinical practice in North West
      England.
AB  - Several aspects of the management of suspected testicular torsion are
      controversial. A questionnaire was mailed to all 33 consultant urologists in the
      North West region of England to elicit their policies for routine clinical
      management. 29 of 33 questionnaires were returned (2 incomplete). As regards
      radiological investigation, 4 consultants always request ultrasound examination;
      the others do not favour routine imaging. When the diagnosis of testicular
      torsion is confirmed at operation, all consultants would perform bilateral
      testicular fixation, although with considerable variations in technique; most use
      Vicryl sutures (66%) and three-point fixation (57%). One-third would do an
      ipsilateral orchidopexy if there was no clear evidence of testicular torsion at
      operation. The variation revealed by this survey prompted an attempt to formulate
      a protocol for management. A review of the published work indicates that, in
      cases of proven testicular torsion, treatment should include bilateral fixation
      with delayed-absorption or non-absorbable sutures; fixation should be at three
      points. When torsion is not found at operation, there is no evidence of benefit
      from orchidopexy.

PMID- 11983767
TI  - An unexplained foreign body in the myocardium.

PMID- 11983768
TI  - A plastic explosive by mouth.

PMID- 11983769
TI  - Cardiac myxoma with three recurrences.

PMID- 11983770
TI  - Grease-gun injury to the penis.

PMID- 11983771
TI  - More changed against than changing? Public health in the new NHS.

PMID- 11983772
TI  - The real Doctor Frankenstein?

PMID- 11983773
TI  - The death of Claudius.

PMID- 11983774
TI  - Fusidic acid monotherapy.

PMID- 11983775
TI  - Emergency ambulance triage.

PMID- 11983776
TI  - Attitudes to torture.

PMID- 11983778
TI  - Back pain--whose responsibility?

PMID- 11983779
TI  - Decline in rehabilitation services.

PMID- 11983780
TI  - Revalidation of the retired.

PMID- 11983781
TI  - The man who walks backwards.

PMID- 11983782
TI  - Clinical skills in final year medical students.

PMID- 11983783
TI  - Decline in rehabilitation services.

PMID- 11983784
TI  - Earth-eating.

PMID- 11983785
TI  - Mystery syndromes.

PMID- 11983786
TI  - Ecstasy in the brain: a model for neuroimaging.

PMID- 11983787
TI  - Characteristics of psychotic disorder due to traumatic brain injury: an analysis
      of case studies in the literature.
AB  - The authors analyzed data from 69 published case studies of Psychotic Disorder
      Due to Traumatic Brain Injury (PDTBI) in order to describe its common
      characteristics and assist in its diagnosis and differentiation from
      schizophrenia. The majority of these PDTBI patients were males with onset of
      symptoms occurring within the first 2 years after moderate to severe head injury.
      A majority showed abnormalities on MRI/CT and EEG with localization in the
      frontal and temporal areas. The general presentation included delusions and
      hallucinations without co-occurring negative symptoms. The findings demonstrate
      that patients with PDTBI have a profile that distinguishes itself from
      schizophrenia.

PMID- 11983788
TI  - The spectrum of organic depersonalization: a review plus four new cases.
AB  - Depersonalization and derealization are commonly reported in the general
      population as a response to stress. The symptoms have also been described in
      patients with a primary psychiatric or organic diagnosis, where their secondary
      status precludes a DSM-IV diagnosis of depersonalization disorder. The authors
      present 4 new cases of depersonalization in patients with an underlying organic
      condition, along with 47 cases from the literature in which the available
      information permits diagnosis of organic depersonalization. Information from case
      series documenting depersonalization in the context of medical illnesses is also
      presented and the underlying etiology discussed. Epilepsy and migraine appear to
      be the disorders most commonly associated with depersonalization. Left-sided
      temporal lobe dysfunction and anxiety are suggested as factors in the development
      of depersonalization; however, further studies are needed to determine the
      relationship. The introduction to the DSM-IV of an organic subtype of
      depersonalization disorder would facilitate research in this area.

PMID- 11983789
TI  - Beyond Wernicke's: a lexicon of eponyms in psychiatry.
AB  - Because no one has ever composed a glossary of psychiatry's numerous eponyms, the
      author collected eponymous signs and syndromes for a behavioral lexicon. Eponyms
      are included if they recall a real person, if they have special relevance to
      psychiatry, and if they describe an abnormal symptom or syndrome that we consider
      clinically important today, even if American physicians no longer favor the
      eponym. The author used MEDLINE and Campbell's Psychiatric Dictionary to locate
      candidates for the glossary. A brief definition and suggested reference accompany
      each entry.

PMID- 11983790
TI  - Do testosterone levels relate to aggression in elderly men with dementia?
AB  - The aim of this study was to determine if testosterone and estrogen levels
      correlate with aggression in older men with dementia. Plasma total and free
      testosterone and estrogen levels and scores for behavioral disturbances, in
      particular aggression, were measured in 50 elderly males who had a diagnosis of
      dementia. Aggression was analyzed separately from agitation. Pearson correlations
      were calculated to determine the association between testosterone and estrogen
      and aggression. Linear regression analyses determined the influence of hormone
      levels on aggression, controlling for age, medical burden, and dementia severity.
      Free testosterone levels showed significant positive correlations with measures
      of aggression. Estrogen levels showed significant negative correlations with
      measures of aggression.

PMID- 11983791
TI  - Symptoms of delirium among elderly medical inpatients with or without dementia.
AB  - This study examined the frequencies of the 10 symptoms of delirium identified in
      DSM-III-R among patients with delirium (DSM-III-R criteria) who did or did not
      have dementia. The prevalence of each symptom, the numbers of symptoms, and the
      combinations of symptoms were determined among 322 elderly medical inpatients
      classified into one of four groups: delirium and dementia (n=128), delirium only
      (n=40), dementia only (n=94), or neither (n=60). Symptoms were assessed at the
      time of diagnosis and independently (by use of a different scale) within 24 hours
      of diagnosis. Delirium appeared to be phenomenologically similar among patients
      with and those without dementia, although patients with dementia had more
      psychomotor agitation at the time of diagnosis and more disorganized thinking and
      disorientation at the second assessment.

PMID- 11983792
TI  - Brain lesions in patients visiting a memory clinic with postconcussional sequelae
      after mild to moderate brain injury.
AB  - Postconcussional disorder after a relatively mild head injury is common. Although
      a partial organic etiology is presumed, little imaging evidence exists for this
      assumption. In this study, patients with mild to moderate brain injury (median
      Glasgow Coma Scale score of 14) had more parenchymal brain lesions than control
      subjects (P=0.02). Additionally, the authors investigated the potential of
      quantifying brain injury by the magnetization transfer ratio (MTR). The curve
      amplitude of the MTR histogram was used as a measure of normal white matter.
      Patients had a lower curve amplitude than control subjects (P=0.008). This study
      provides evidence of persistent traumatic brain alterations in patients who
      sustained a relatively mild traumatic brain injury.

PMID- 11983793
TI  - Psychosensory symptoms in combat veterans with posttraumatic stress disorder.
AB  - Psychosensory symptoms have relevance to the study of chronic posttraumatic
      stress disorder (PTSD), given that their presence is associated with limbic
      system dysfunction and that several features of chronic PTSD suggest that it,
      too, may be associated with limbic dysfunction. The Iowa Interview for Partial
      Seizure-like Symptoms (IIPSS), a measure of psychosensory symptoms, was
      administered to a PTSD group and a comparison group. The PTSD group generated
      significantly higher IIPSS scores than did the other group. Within the PTSD
      group, higher IIPSS scores were associated with significantly more severe PTSD
      symptoms, dissociative symptoms, aggression, and overall psychopathology.

PMID- 11983794
TI  - Spatiotemporal visual processing in schizophrenia.
AB  - Studies examining visual processing in schizophrenia have provided inconsistent
      results. In this study, the authors measured static and dynamic visual contrast
      sensitivity (CS) in patients with schizophrenia (n=20) and control subjects
      (n=15). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. In
      the static condition, the patients with schizophrenia showed reduced CS in the
      spatial frequency range of 2.9-14.4 cycles per degree of visual angle (c/d). In
      the dynamic condition, CS loss was present over the whole range tested (0.5-14.4
      c/d). Higher Simpson-Angus scores and higher doses of antipsychotic medication
      were associated with more severe CS deficits. These results suggest that the
      hypodopaminergic state induced by antipsychotic medication may produce
      parkinsonian visual impairments in schizophrenia patients.

PMID- 11983795
TI  - The Pocket Smell Test: successfully discriminating probable Alzheimer's dementia
      from vascular dementia and major depression.
AB  - The present study extended previous work on olfactory dysfunction (odor
      identification deficits) by using the Pocket Smell Test (PST) to discriminate
      between groups of patients with Alzheimer's disease (AD), vascular dementia
      (VaD), and major depression (MD). Sixty patients meeting the DSM-IV criteria for
      either AD, VaD, or MD (20 per group) underwent assessment with the PST, a three
      item screening measure of odor identification, and the Mini-Mental State
      Examination (MMSE). Patients with AD scored significantly lower than patients
      with either VaD or MD on the PST, even after controlling for MMSE scores. A PST
      score of > or =1 (i.e., 1 or 0 correct) discriminated between patients with and
      without AD with a classification accuracy of 95% (sensitivity 100%, specificity
      92.5%). Olfactory assessment may be of diagnostic utility in the differential
      diagnosis of AD versus VaD versus MD in elderly patients.

PMID- 11983796
TI  - Divalproex in the management of neuropsychiatric complications of remote acquired
      brain injury.
AB  - A retrospective chart review was conducted on 11 patients with a remote history
      of acquired brain injury (ABI) referred for psychiatric treatment who were
      treated with divalproex sodium alone or in combination with other psychotropic
      medications. The patients were highly heterogeneous. They had a variety of
      psychiatric symptoms and frequently received concomitant psychotropic
      medications. The mean daily dose of divalproex was 1,818+/-791 mg/day, serum
      valproic acid level 85.6+/-29.6 microg/ml. Mean Clinical Global Impression
      improvement score was 1.9+/-0.5. This is the largest postacute case series
      reported. It demonstrates that divalproex sodium is well tolerated and effective
      in reducing a broad range of neurobehavioral symptoms in psychiatric patients
      with a remote history of ABI.

PMID- 11983797
TI  - Efficacy and safety of venlafaxine-ECT combination in treatment-resistant
      depression.
AB  - Thirteen patients with treatment-resistant major depression were given
      venlafaxine, at doses ranging from 150 mg to 375 mg, combined with ECT. Propofol
      was used as an anesthetic. Ten of 13 (76.9%) were considered responsive to
      combined ECT-venlafaxine treatment, and positive responses were not associated
      with venlafaxine doses. An asystole episode was observed in 4 patients; these
      patients had received significantly higher doses of venlafaxine (P<0.01).
      Treatment seems to be safe at venlafaxine doses <300 mg/day. At higher doses,
      with propofol used as anesthetic, the possibility of asystole cannot be ruled
      out. A possible additive effect of high-dose venlafaxine and propofol-blocking
      sodium channels are discussed.

PMID- 11983798
TI  - Interictal schizophrenia-like psychosis in a patient with double cortex syndrome.
AB  - The authors report a female patient with sporadic double cortex syndrome who
      manifested recurrent interictal schizophrenia-like psychoses. She had no
      mutations in the doublecortin gene but a pericentric inversion of chromosome 9.
      Neurodevelopmental disturbances and seizures may be associated with her mental
      dysfunction.

PMID- 11983799
TI  - Clinicopathologic case report: akinetic mutism with findings of white matter
      hyperintensity.

PMID- 11983801
TI  - An essay on the shaking palsy. 1817.

PMID- 11983802
TI  - Risk factors for treatment-resistive methamphetamine psychosis.

PMID- 11983803
TI  - Adjunctive modafinil in ALS.

PMID- 11983804
TI  - Temporal lobe structural lesion in a case of posttraumatic stress disorder.

PMID- 11983805
TI  - Insight and neurocognitive function in schizophrenia.

PMID- 11983807
TI  - Regulation of global and specific mRNA translation by amino acids.
AB  - A continuous supply of a complete complement of essential amino acids is a
      prerequisite for maintenance of optimal rates of protein synthesis in both liver
      and skeletal muscle. Deprivation of even a single essential amino acid causes a
      decrease in the synthesis of essentially all cellular proteins through an
      inhibition of the initiation phase of mRNA translation. However, the synthesis of
      all proteins is not repressed equally. Specific subsets of proteins, in
      particular those encoded by mRNAs containing a 5'-terminal oligopyrimidine (TOP)
      motif, are affected to a much greater extent than most proteins. The specific
      decrease in TOP mRNA translation is a result of an inhibition of the ribosomal
      protein S6 kinase, S6K1, and a concomitant decline in S6 phosphorylation.
      Interestingly, many TOP mRNAs encode proteins involved in mRNA translation, such
      as elongation factors eEF1A and eEF2, as well as the ribosomal proteins. Thus,
      deprivation of essential amino acids not only directly and rapidly represses
      global mRNA translation, but also potentially results in a reduction in the
      capacity to synthesize protein.

PMID- 11983808
TI  - Biotin supply affects expression of biotin transporters, biotinylation of
      carboxylases and metabolism of interleukin-2 in Jurkat cells.
AB  - Biotin supply may affect transcription of genes and biotinylation of proteins in
      cells. In this study, Jurkat cells were used to model effects of biotin supply on
      biotin homeostasis and interleukin-2 metabolism in immune cells. Cells were
      cultured in media containing deficient (25 pmol/L), physiologic (250 pmol/L), or
      pharmacologic concentrations (10,000 pmol/L) of biotin for 4 wk. Activities of
      the biotin-dependent enzyme propionyl-CoA carboxylase paralleled the biotin
      concentrations in media [pmol bicarbonate fixed/(min x 10(6) cells)]: 1.9 +/- 0.7
      (25 pmol/L biotin) vs. 19 +/- 1.2 (250 pmol/L biotin) vs. 40 +/- 2.0 (10,000
      pmol/L biotin). Cells responded to biotin deficiency with increased expression of
      biotin transporter genes. Biotin-deficient cells maintained normal biotinylation
      of histones but contained reduced levels of biotinylated carboxylases, suggesting
      compartmentalization of intracellular biotin distribution. Rates of cell
      proliferation and activities of the apoptotic enzyme caspase-3 were similar among
      treatment groups, suggesting that net proliferation was not affected by biotin
      status. Net secretion of interleukin-2 by Jurkat cells was inversely associated
      with the biotin concentration in media [kU/(L x 24 h x 10(6) cells)]: 21 +/- 1.8
      (25 pmol/L biotin) vs. 15 +/- 5.4 (250 pmol/L biotin) vs. 6.1 +/- 1.8 (10,000
      pmol/L biotin), suggesting increased secretion or decreased internalization of
      interleukin-2 by biotin-deficient cells. This study provides evidence that biotin
      supply affects biotinylation of proteins, gene expression and metabolism of
      interleukin-2 in Jurkat cells. The physiological significance of effects of
      biotin status on metabolism of interleukin-2 remains to be elaborated.

PMID- 11983809
TI  - The leptin defense against wasting is abolished in the IL-2-deficient mouse model
      of inflammatory bowel disease.
AB  - Anorexia is a major complication of inflammatory bowel disease (IBD). We
      postulated that chronic intestinal inflammation with increased proinflammatory
      cytokines elevates serum leptin concentration, thereby contributing to anorexia.
      This hypothesis was studied in interleukin-2-deficient (IL-2(-/-)) mice, a model
      of IBD with elevated proinflammatory cytokine production. IL-2(-/-), wild-type
      pair-fed and wild-type control male mice (8 wk old) were fed regular laboratory
      mouse food for 2 wk. The IL-2(-/-) and pair-fed groups consumed less food and
      lost weight. Serum leptin concentrations in the IL-2(-/-) mice in the fed state
      were lower than controls, but not different from pair-fed mice, and paradoxically
      increased in the starved state to levels significantly higher than both starved
      control and pair-fed groups. This result did not change when serum leptin was
      adjusted for amount of body fat. These data show abnormal leptin responses in IL
      2(-/-) mice with increased leptin concentrations disproportionate to fat mass and
      prevention of the normal decline in leptin with food restriction.

PMID- 11983810
TI  - Dietary glutathione protects rats from diabetic nephropathy and neuropathy.
AB  - Recently, much attention has focused on the role of oxidative stress in the
      various forms of tissue damage in patients with diabetes. The aim of this study
      was to examine the involvement of oxidative stress in the progression of kidney
      dysfunction and neuropathy in diabetes and to evaluate the potential usefulness
      of glutathione (GSH) in diabetes. We examined the effect that treatment of
      streptozotocin (STZ)-induced diabetic rats with GSH has on the renal and neural
      functions. Diabetic rats were treated with 1 g/100 g GSH as a dietary supplement.
      GSH significantly suppressed the diabetes-induced increase in urinary 8-hydroxy
      2'-deoxyguanosine, one of the markers of oxidative stress. It also prevented the
      diabetes-induced increases in albumin and creatinine in urine. The diabetes
      induced increase in the tail flick reaction time to thermal stimuli also was
      normalized by treatment with dietary GSH. In conclusion, GSH treatment can
      beneficially affect STZ-induced diabetic rats, with preservation of in vivo renal
      and neural function. This suggests a potential usefulness of dietary GSH
      treatment to reduce diabetic complications.

PMID- 11983811
TI  - Early posthatch starvation induces myonuclear apoptosis in chickens.
AB  - The effect of early posthatch starvation on myonuclear apoptosis was examined in
      chickens. Male broiler chickens were or were not provided feed for the first 3-d
      posthatch. Subsequently, all chickens were provided feed for an additional 4-d
      posthatch. Chickens were killed at 3- and 7-d posthatch, and the pectoralis
      thoracicus was harvested, fixed and embedded in paraffin. Muscle sections were
      labeled with the terminal deoxynucleotidyl transferase histochemical staining
      technique to identify apoptotic nuclei. At 3- and 7-d posthatch, there was a
      significantly (P < 0.05) smaller myofiber cross-sectional area for the starved
      compared with the fed chickens. A larger proportion (P < 0.05) of apoptotic
      nuclei relative to total nuclei was observed in the starved compared to the fed
      chickens killed at 3-d posthatch, but the proportion of apoptotic nuclei relative
      to total nuclei did not differ (P > 0.05) between the starved and fed chickens
      killed at 7-d posthatch. It appears that apoptosis is a mechanism contributing to
      the smaller myofiber size observed when feed is not provided early posthatch.

PMID- 11983812
TI  - Octanoate attenuates adipogenesis in 3T3-L1 preadipocytes.
AB  - Preadipocytes exposed to octanoate accumulate less lipid than cells exposed to
      long-chain fatty acids. This effect of octanoate involves significant attenuation
      of expression of key adipogenic transcription factors, including peroxisome
      proliferator-activated receptor (PPAR)gamma, steroid regulatory binding element
      protein (SREBP)-1c and CCAAT element binding protein (C/EBPalpha) at both the
      mRNA and protein levels. Expression of differentiation markers, including
      adipocyte fatty acid binding protein (ALBP), glycerol-3-phosphate dehydrogenase
      (GPDH) and leptin, was also significantly diminished by octanoate. However,
      octanoate did not prevent the decrease in preadipocyte factor-1 (Pref-1)
      expression that occurs during adipogenesis, nor did it inhibit the early
      induction of C/EBPbeta,delta. Treatment with synthetic PPARgamma ligands
      partially offset the inhibitory effect of octanoate on differentiation. Ectopic
      expression of PPARgamma2 in 3T3-L1 cells partially restored lipid accretion and
      GPDH activity in octanoate-treated cells. Adding octanoate together with
      troglitazone attenuated the effects of troglitazone on adipocyte differentiation
      in both normal 3T3-L1 cells and engineered 3T3-L1 cells that expressed ectopic
      PPARgamma2, implying that octanoate might compete against troglitazone for its
      binding to PPARgamma. These results suggest that octanoate may block adipogenesis
      at least in part by its influence on the expression/activation of PPARgamma.

PMID- 11983813
TI  - Starving affects CDX gene expression during small intestinal development in the
      chick.
AB  - The small intestine of the chicken undergoes intensive changes in the immediate
      posthatch period, increasing in size and developing crypts, villi and mature
      enterocytes. During this time, chicks are also transferring from nutrition based
      on the lipid-rich yolk to exogenous carbohydrate-rich feeds. The cdx homeobox
      genes participate in axial patterning and in definition of cell identity in
      embryos, and some cdx genes remain active postpartum in organs such as the
      intestine. In this study, the transcription patterns of two of these genes, cdxA
      and cdxB, were examined in the small intestine of the embryo and posthatch chick;
      in addition, the effects on these genes of starving for 48 h at hatch were
      examined. Both cdx transcription factors were upregulated toward the time of
      hatch and were observed in proliferating enterocytes; this enhanced expression
      continued posthatch. Distribution of cdxA changed with age and was found at
      higher concentrations in mature enterocytes. Starving from 0 to 48 h posthatch
      retarded growth and decreased enterocyte proliferation and expression of cdxA and
      cdxB. After access to feed, expression of cdx genes was enhanced. Chicken
      homeobox genes cdxA and cdxB are expressed in all enterocytes during embryonic
      and posthatch development; however, cdxA may have a role in enterocyte maturation
      posthatch. CdxB was expressed later in development then previously reported.

PMID- 11983814
TI  - Fructose intake increases hyperlipidemia and modifies apolipoprotein expression
      in apolipoprotein AI-CIII-AIV transgenic mice.
AB  - Fructose intake has increased steadily during the past two decades. The objective
      of this study was to determine the effect of fructose intake on lipid metabolism
      in apolipoprotein (apo) AI-CIII-AIV transgenic (Tg) mice that have severe
      hypertriglyceridemia and moderate hypercholesterolemia. Tg and control mice were
      fed for 9 mo a commercial nonpurified diet and had free access to water or 250
      g/L fructose solution. In Tg mice, fructose intake increased triglycerides and
      cholesterol but did not induce insulin resistance. There were no differences in
      human hepatic apo AI and apo CIII mRNA levels in fructose-fed mice compared with
      untreated mice, but apo AIV mRNA was greater, indicating a differential
      expression of the apo AI and apo AIV genes in response to dietary perturbations.
      Interestingly, the plasma concentration of the three human apolipoproteins was
      enhanced in fructose-fed Tg mice compared with untreated Tg mice. Our data
      suggest that long-term fructose consumption had strong adverse effects in this
      hyperlipidemic mouse model.

PMID- 11983815
TI  - Triacylglycerol molecular weight and to a lesser extent, fatty acid positional
      distribution, affect chylomicron triacylglycerol composition in women.
AB  - Postprandial composition of chylomicron triacylglycerols (TAG) and their
      clearance may be affected by the molecular weight of TAG, their fatty acid (FA)
      combinations and the positional distribution of FA in TAG. Delayed postprandial
      TAG clearance is a risk factor for cardiovascular disease. However, due to the
      complexity of traditional analysis methods, the composition of individual TAG
      molecules is frequently overlooked. In this study, chylomicron TAG molecular
      weight distribution and regioisomerism were followed in 10 healthy female
      volunteers after two fat loads with identical FA composition but different
      positional distributions (palm oil and transesterified palm oil). An efficient
      tandem mass spectrometric method of analysis was applied. During the 6-h
      observation period, the relative concentrations of TAG with 48:2 [48 acyl carbons
      and 2 double bonds (ACN:DB)], 50:3 and 50:2 decreased, whereas the proportions of
      48:0 (tripalmitin), 52:3 and 54:4 remained constant and the proportion of 54:3
      (triolein) increased (P < 0.05). The existence of seven regioisomers containing
      palmitic, oleic and linoleic acids in different sn-positions was studied. The
      amount of 1,3-dipalmitoyl-2-oleoyl-sn-glycerol was less (P < 0.05) 1.5 h
      postprandially than at 2-5 h after palm oil, and less (P < 0.05) at 1.5 h than at
      2-6 h after transesterified palm oil. This may be an indication of a loss of
      palmitic acid in the gut. Taken together, TAG molecular weight composition and to
      a lesser extent, positional distribution, seem to affect the rates of chylomicron
      TAG clearance in humans.

PMID- 11983816
TI  - Dietary magnesium depletion affects metabolic responses during submaximal
      exercise in postmenopausal women.
AB  - Magnesium is an essential mineral that is required for optimal biological
      function including energy metabolism. Although national nutritional surveys
      indicate that usual magnesium intakes do not meet recommendations, particularly
      among older women, diet-induced magnesium depletion is considered rare among
      humans without concurrent illness. We examined the effects of dietary magnesium
      restriction on biochemical measures of magnesium nutriture and physiologic
      responses during submaximal exercise in 10 postmenopausal women, 45-71 y old, not
      receiving hormone replacement therapy. The women consumed diets containing
      conventional foods with varying magnesium content totaling 112 mg/8.4 MJ (2000
      kcal) supplemented with 200 mg magnesium daily for 35d (control), then 112 mg/8.4
      MJ for 93d (depletion) followed by 112 mg/8.4 MJ supplemented with 200 mg
      magnesium/d for 49d (repletion) in a depletion-repletion experiment. RBC
      magnesium concentration (P < 0.05), magnesium retention (P < 0.05) and skeletal
      muscle magnesium concentration (P < 0.05) decreased when dietary magnesium was
      restricted. Peak oxygen uptake, total and cumulative net oxygen uptake determined
      by using indirect calorimetry and peak heart rate increased (P < 0.05) during
      standardized submaximal work with restricted compared with adequate dietary
      magnesium. These findings indicate that dietary magnesium depletion can be
      induced in otherwise healthy women; it results in increased energy needs and
      adversely affects cardiovascular function during submaximal work. This may also
      explain previous observations of increased energy cost during standardized
      exercise in physically active men and women considered to have reduced magnesium
      nutriture.

PMID- 11983817
TI  - Use of an oral/intravenous dual-label stable-isotope protocol to determine folic
      acid bioavailability from fortified cereal grain foods in women.
AB  - Folic acid fortification, mandatory in the United States, is currently being
      considered by the UK. The hypothesis that the matrix of some cereal-product
      vehicles may result in low fortificant bioavailability was tested using a dual
      oral/intravenous (i.v.) isotopic-label approach, which was evaluated
      concurrently. Fifteen women received 225 microg oral folate (capsules, fortified
      white bread and fortified branflakes), mainly as folic acid labeled with (13)C on
      6 carbons of the benzoyl ring ((13)C(6)-PteGlu), followed by i.v. injection of
      100 microg folic acid labeled with (2)H on 4 hydrogens of the glutamic acid group
      ((2)H(4)-PteGlu). The urinary excretion ratio (UER) in intact folate of the
      percentage of labeled oral dose excreted divided by the percentage of i.v. dose
      excreted was used as the primary index of absorption. The geometric mean (95%
      confidence interval) UER for folic acid capsules was 3.68 (1.90, 7.14) at 24 h
      and 2.18 (1.24, 3.83) at 48 h. Because these were significantly in excess of 1.0,
      indicative of 100% absorption of the oral dose, it was concluded that oral and
      i.v. labeled folic acid are handled differently by the body and that "absolute"
      absorption cannot be calculated. Compared with the 48-h UER for folic acid
      capsules, the "relative" 48-h UER for white bread and branflakes was 0.71 and
      0.37, respectively, indicating that some cereal-based vehicles may inhibit
      absorption of fortificant. However, even the validity of this "relative" approach
      is questioned.

PMID- 11983818
TI  - The decrease in body fat in mice fed conjugated linoleic acid is due to increases
      in energy expenditure and energy loss in the excreta.
AB  - We carried out energy balance studies in four groups of young, growing, 5-wk-old
      Balb-C mice (n = 12/group) that were either food restricted or nonrestricted and
      fed high fat diets (38 energy%) with or without 0.93 g/100 g conjugated linoleic
      acid (CLA) for 39 d. The energy in carcasses, excreta and food was measured in a
      bomb calorimeter. CLA lowered the percentage of the energy intake that was stored
      in the body from 1.9 +/- 0.8 to -2.3 +/- 0.7% (mean +/- SD, P < 0.05) in the
      nonrestricted mice and from 1.4 +/- 1.3 to -2.9 +/- 0.7% (P < 0.05) in the
      restricted mice. Thus, the CLA-treated mice had a net loss of body energy. The
      percentage of the energy intake eliminated in the excreta increased from 7.6 +/-
      0.9% in controls to 8.7 +/- 1.0% (P < 0.05) in the CLA-treated mice that were
      nonrestricted and from 7.3 +/- 0.8 to 8.4 +/- 0.6 (P < 0.05) in the restricted
      mice. The amount of energy ingested minus the amount retained in carcasses and
      excreta equals the energy expenditure. The percentage of the energy intake that
      was expended as heat increased from 90.5 +/- 1.2 in controls to 93.6 +/- 1.5% (P
      < 0.05) in the CLA-treated nonrestricted mice and from 91.3 +/- 1.5 to 94.5 +/-
      1.0% (P < 0.05) in the restricted mice. The lower energy storage in the CLA-fed
      mice was accounted for by an increase in the energy expenditure (74%) and by an
      increase in energy lost in the excreta (26%). Feeding CLA also increased liver
      weight, which may warrant further studies on the safety of CLA.

PMID- 11983819
TI  - Brown algae fucoxanthin is hydrolyzed to fucoxanthinol during absorption by Caco
      2 human intestinal cells and mice.
AB  - The metabolic fate in mammals of dietary fucoxanthin, a major carotenoid in brown
      algae, is not known. We investigated the absorption and metabolism of fucoxanthin
      in differentiated Caco-2 human intestinal cells, a useful model for studying the
      absorption of dietary compounds by intestinal cells. Fucoxanthin was taken up by
      Caco-2 cells incubated with micellar fucoxanthin composed of 1 micromol/L
      fucoxanthin, 2 mmol/L sodium taurocholate, 100 micromol/L monoacylglycerol, 33.3
      micromol/L fatty acids and 50 micromol/L lysophosphatidylcholine. Fucoxanthinol,
      the deacetylated product of fucoxanthin, was also found in both medium and cells,
      with its level increasing significantly in a time-dependent manner. No conjugated
      forms of fucoxanthin and fucoxanthinol were found in either medium or cells. In
      the animal study, fucoxanthinol (10.4 +/- 5.3 nmol/L plasma, n = 4) was detected
      in plasma of mice 1 h after intubation of 40 nmol fucoxanthin. These results
      indicate that dietary fucoxanthin is incorporated as fucoxanthinol, the
      deacetylated form, from the digestive tract into the blood circulation system in
      mammals.

PMID- 11983820
TI  - Net interorgan transport of L-glutamate in rats occurs via the plasma, not via
      erythrocytes.
AB  - Glutamate is concentrated within RBC, but this intracellular glutamate is often
      ignored in studies of glutamate metabolism in vivo. The objective of this work
      was to determine the size of the plasma and cellular glutamate pools in rat blood
      and to clarify the role of RBC in the interorgan transport of glutamate.
      Approximately 20% of whole-blood glutamate was associated with isolated RBC
      membranes, but this was easily removed by washing with high salt solutions.
      Arterial plasma glutamate levels were relatively stable and did not show marked
      differences with starvation, streptozotocin diabetes or feeding 60% casein diets.
      In rats fed 5% casein, the plasma glutamate level was slightly higher (P < 0.05)
      than in most other groups. In contrast, RBC glutamate levels showed considerable
      variation. In rats consuming 5% casein, cellular glutamate levels were
      approximately 100% higher (P < 0.05) than in control, starved, diabetic or 20 or
      60% casein-fed rats. Cellular glutamate levels were also higher (P < 0.05) in
      rats fed 60% casein than in those consuming 20% casein or the control diet. Rat
      erythrocytes in vitro did not take up or release free glutamate, confirming that
      they do not possess a glutamate transporter. Arteriovenous difference
      measurements across the portal drained viscera indicated a net glutamate release
      into the portal vein in control, 60% casein-fed and diabetic rats. In all cases,
      the net change in blood glutamate across the tissue occurred via the plasma, with
      no change in cellular glutamate levels. Therefore analyses of glutamate
      metabolism in rats in vivo may be made confidently using measurements of either
      whole-blood or plasma glutamate concentrations.

PMID- 11983821
TI  - Transgenic rice is a source of iron for iron-depleted rats.
AB  - Iron deficiency is one of the most prevalent nutrient deficiencies in the world.
      A sustainable solution to dietary iron deficiency may be achieved in part by
      increasing bioavailable iron in seeds used for foods such as rice. Because
      ferritin is used as a natural source of iron in the early development of humans,
      other animals and plants, the bioavailability of iron in rice seeds, provided in
      amounts equal to ferrous sulfate, and in transgenic rice with ferritin was tested
      in iron-deficient rats. A standard hemoglobin (Hb) repletion bioassay was used
      with rats made anemic followed by complete diets containing equivalent amounts of
      iron as FeSO(4) or one of three different bioengineered rice varieties (Kitaake
      and two transgenic derivatives with ferritin targeted to the seed, FK11 and
      FK22). Rice diets were as effective as the FeSO(4) diet in replenishing
      hematocrit, Hb concentration and liver iron concentrations. These data suggest
      that Mendelian and biotechnological approaches to manipulating ferritin
      expression of seed iron in rice may contribute to a sustainable solution to
      global problems of iron deficiency.

PMID- 11983822
TI  - Dietary sesame seed and its lignans inhibit 2,7,8-trimethyl- 2(2'-carboxyethyl)-6
      hydroxychroman excretion into urine of rats fed gamma-tocopherol.
AB  - We showed previously that dietary sesame seed and its lignans elevate the
      tocopherol concentration in rats. To clarify their effect on tocopherol
      metabolism, we determined in this study the urinary excretion of 2,7,8-trimethyl
      2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol metabolite,
      in rats fed sesame seed or its lignans. Rats were fed diets with or without
      sesame seed for 28 d in Experiment 1, and for 1, 3 and 7 d in Experiment 2. On d
      28, dietary sesame seed elevated (P < 0.05) gamma-tocopherol concentrations in
      liver, kidney, brain and serum, and decreased (P < 0.05) urinary excretion of
      gamma-CEHC. The excretion was completely inhibited by feeding sesame seed on d 1
      and 3. In Experiment 3, the effects of dietary sesamin and sesaminol (major
      lignans in sesame seed) or ketoconazole (a selective inhibitor of cytochrome
      P(450) (CYP)3A on urinary excretion of gamma-CEHC in rats fed gamma-tocopherol
      were examined. The urinary gamma-CEHC in rats fed sesamin or sesaminol was
      markedly lower than in rats fed gamma-tocopherol alone (P < 0.05). Dietary
      ketoconazole also inhibited (P < 0.05) urinary excretion of gamma-CEHC, and
      elevated (P < 0.05) gamma-tocopherol concentrations in tissues and serum of rats
      fed gamma-tocopherol. These data suggest that sesame seed and its lignans elevate
      gamma-tocopherol concentration due to the inhibition of CYP3A-dependent
      metabolism of gamma-tocopherol.

PMID- 11983823
TI  - Dietary fructans, but not cellulose, decrease triglyceride accumulation in the
      liver of obese Zucker fa/fa rats.
AB  - This study was designed to compare the effects of dietary supplementation with
      nondigestible carbohydrates, differing in fermentability by colonic bacteria, on
      hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were
      divided into three groups: a control group that received the basal diet, a
      fructan group that received 10 g highly fermented Synergy 1/100 g diet and a
      cellulose group that received 10 g poorly fermented Vivapur Microcrystalline
      cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower
      body weight and less triacylglycerol accumulation in the liver as assessed in
      vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical
      and histochemical analysis compared with the control and/or cellulose groups. The
      high fermentation of fructans compared with cellulose was reflected by greater
      cecal contents and by a twofold greater propionate concentration in the portal
      vein of rats fed fructan compared with those fed cellulose. By measuring the
      capacity of hepatocytes isolated from liver of Zucker rats to synthesize
      triglycerides or total lipids from different precursors, we showed that
      propionate, at the concentrations measured in the portal vein of rats treated
      with fructan, selectively decreased the incorporation of acetate into total
      lipids, a phenomenon that could contribute, along with the lower energy intake,
      to less triglyceride accumulation in the liver of obese Zucker rats fed dietary
      fructans.

PMID- 11983824
TI  - Apoptosis plays a distinct role in the loss of precursor lymphocytes during zinc
      deficiency in mice.
AB  - Lymphopenia is a characteristic of zinc deficiency, which is associated with
      massive loss of pre-B and pre-T cells from the primary lymphoid organs of zinc
      deficient mice that have elevated serum corticosterone (CS). We examined whether
      this naturally elevated glucocorticoid level is associated with increased
      apoptotic loss of pre-T cells in the thymus of A/J and CAF1/J mice. In three
      experiments, partially atrophied thymuses were removed from 20 marginally zinc
      deficient (ZD) young adult mice and cultured for 6 h in parallel with thymocytes
      prepared from 17 adequately fed mice. Thymocyte immunophenotyping combined with
      flow cytometric cell cycle analysis was used to identify the degree of apoptotic
      cell death among thymocytes of the two dietary groups, which were compared in the
      absence of in vivo phagocytosis. Apoptosis was enhanced 50-300% among pre-T cells
      (CD4+CD8+) prepared from ZD mice. This resulted in a 38% shrinkage of the thymic
      pre-T cell compartment, which was associated with an 80% decrease in thymic cell
      number. Pro-T cells (CD4-CD8-) and mature T cells (CD4+CD8-, CD4-CD8+), which
      express higher levels of Bcl-2 protein, survived ZD to a greater extent and
      formed a greater proportion of the remaining thymocyte population in ZD mice.
      Collectively, these data show that heightened degrees of apoptotic cell death
      induced in vivo by CS-disrupted thymic T cell lymphopoiesis, identifies the means
      of disruption of marrow B cell lymphopoiesis and explains the appearance of
      lymphopenia.

PMID- 11983825
TI  - Supplemental fructooligosaccharides and mannanoligosaccharides influence immune
      function, ileal and total tract nutrient digestibilities, microbial populations
      and concentrations of protein catabolites in the large bowel of dogs.
AB  - The goal of this study was to examine whether supplemental fructooligosaccharides
      (FOS) and (or) mannanoligosaccharides (MOS) influenced indices of gut health of
      dogs. Adult female dogs (n = 4) surgically fitted with ileal cannulas were fed a
      dry, extruded, kibble diet twice daily. At each feeding, the following treatments
      were administered: 1) Control (no FOS or MOS); 2) 1 g FOS; 3) 1 g MOS; or 4) 1 g
      FOS + 1 g MOS. Fecal, ileal and blood samples were collected during the last 4 d
      of each 14-d period to measure protein catabolite concentrations, microbial
      populations, immune characteristics and nutrient digestibilities. Treatment means
      were compared using preplanned orthogonal contrasts. Dogs supplemented with MOS
      had lower (P = 0.05) fecal total aerobes and tended to have greater (P = 0.13)
      Lactobacillus populations. Ileal immunoglobulin (Ig) A concentrations were
      greater (P = 0.05) in dogs supplemented with FOS + MOS vs. control. Lymphocytes
      (% of total white blood cells) were greater (P < 0.05) in dogs supplemented with
      MOS. Serum IgA concentrations also tended (P = 0.13) to be greater in dogs
      supplemented with MOS. Dogs supplemented with FOS and FOS + MOS had lower (P <
      0.05) fecal total indole and phenol concentrations. Dogs supplemented with MOS
      tended to have lower ileal DM (P = 0.149) and OM (P = 0.146) digestibilities vs.
      control. Results of this study suggest that dietary supplementation of FOS and
      MOS may have beneficial effects on colonic health and immune status of dogs.

PMID- 11983826
TI  - Exendin-4, a GLP-1 receptor agonist, modulates the effect of macronutrients on
      food intake by rats.
AB  - The hypothesis that peripheral GLP-1 modulates the effect of macronutrients on
      food intake in rats was tested by administration of its agonist, exendin-4. The
      effect of exendin-4 on food intake suppression and blood glucose after
      carbohydrate, fat and protein preloads was measured. Exendin-4 reduced the effect
      of glucose preloads on food intake only during the first 30 min (P = 0.01) of
      feeding, but had a more prolonged effect when given with corn oil (P < 0.01 at 0
      0.5 h and 0-1 h, P = 0.055 at 0-2 h, and P = 0.07 at 0-3 h) and whey (P < 0.05 at
      0-1 h, P = 0.06 at 0-2 h, and P = 0.07 at 0-3 h) preloads. Blood glucose measured
      over 2 h was reduced at 15 min when given with glucose (P < 0.01), unchanged when
      given with corn oil and increased at 60 and 120 min when given with whey (P <
      0.01). Thus, the effect of exendin-4 on the feeding response depended on the
      composition of the macronutrient preloads and seems to be independent of blood
      glucose concentrations.

PMID- 11983827
TI  - Dietary intake does not account for differences in low iron stores among Mexican
      American and non-Hispanic white women: Third National Health and Nutrition
      Examination Survey, 1988-1994.
AB  - We used nationally representative data from the third National Health and
      Nutrition Examination Survey (NHANES III) to examine the relationship between low
      iron stores (serum ferritin < 12 microg/L) and dietary patterns that might affect
      iron status among Mexican American (MA) and non-Hispanic white (NHW) girls and
      women of reproductive age (12-39 y). Dietary data from the qualitative food
      frequency questionnaire were used to classify subjects into three categories
      (using the 25th and 75th quartile values for NHW) for intake of heme iron,
      nonheme iron, iron absorption enhancers, and iron absorption inhibitors. The
      prevalence of low iron stores was 17.4% among MA (n = 1368) and 7.9% among NHW (n
      = 1473). Compared with high intake, the adjusted odds ratio (OR) for low iron
      stores was 1.80 [95% confidence interval (CI), 1.24-2.62] for medium intake of
      heme iron and 0.48 (95% CI, 0.25-0.91) for low intake of nonheme iron (plus iron
      supplement). Compared with no use, use of vitamin C supplements was associated
      with half the risk of low iron stores (OR = 0.50; 95% CI, 0.29-0.87). Similar
      results were found after income and parity were controlled for, except that the
      protective effect of vitamin C supplements was no longer significant. Even after
      adjustment for sociodemographic and dietary factors, MA women remained at
      increased risk for low iron stores (OR = 1.80; 95% CI, 1.30-2.49) indicating that
      the reasons for the higher prevalence of iron deficiency in MA women warrants
      further investigation.

PMID- 11983828
TI  - Pulse protein feeding pattern restores stimulation of muscle protein synthesis
      during the feeding period in old rats.
AB  - Muscle loss during aging could be related to a lower sensitivity of muscle
      protein synthesis to feeding. To overcome this decrease without increasing
      protein intake, we proposed to modulate the daily protein feeding pattern. We
      showed that consuming 80% of dietary proteins at noon (pulse pattern) improved
      nitrogen balance in elderly women. The present study was undertaken in rats to
      determine which tissues are the targets of the pulse pattern and what mechanisms
      are involved. Male Sprague-Dawley 11- and 23-mo-old rats (n = 32 per age) were
      fed 4 isoproteic (18% protein) meals/d for 10 d. Then half of the rats at each
      age were switched to a 11/66/11/11% repartition of daily proteins (pulse pattern)
      for 21 d. On d 21, rats were injected with a flooding dose of L-(13)C-valine (50
      atom% excess, 150 micromol/100 g body) and protein synthesis rates were measured
      in liver, small intestine and gastrocnemius muscle in either the postabsorptive
      or the fed state. Epitrochlearis muscle degradation rates and plasma amino acid
      concentrations were measured at the same times. The pulse pattern had the
      following effects: 1) it significantly increased liver protein synthesis response
      to feeding and postprandial plasma amino acid concentrations at both ages; 2) it
      restored a significant response to feeding of gastrocnemius muscle protein
      synthesis in old rats; and 3) it had no effect in small intestine or on muscle
      breakdown. Thus, using a pulse pattern could be useful in preventing the age
      related loss of muscle by increasing feeding-induced stimulation of muscle
      protein synthesis.

PMID- 11983829
TI  - The regionalization of PepT1, NBAT and EAAC1 transporters in the small intestine
      of rats are unchanged from birth to adulthood.
AB  - The ontogenetic development of PepT1, NBAT and EAAC1 along the vertical and
      horizontal axes of the rat small intestine was evaluated using semiquantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. The proximodistal profiles of mRNA levels showed that PepT1
      was evenly distributed, whereas NBAT had greater expression in the proximal part,
      and EAAC1 in the distal part. These regionalizations were the same from postnatal
      days 4 to 50. PepT1 and NBAT proteins were detected in the microvilli of
      enterocytes along the length of the villi. NBAT was also found in the cytoplasm.
      Surprisingly, EAAC1 was located exclusively in the microvilli of enterocytes in
      the crypt and the bases of the villi. These protein expression patterns were
      similar in all parts of the small intestine (proximal, median and distal), at all
      ages. We conclude that the expression of PepT1, NBAT or EAAC1 are differently
      regulated according to both the horizontal and vertical axes.

PMID- 11983830
TI  - The effects of short-chain fatty acids on human colon cancer cell phenotype are
      associated with histone hyperacetylation.
AB  - The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial
      fermentation within the colon and is thought to be protective in regard to colon
      carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA,
      a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to
      exert its cellular effects through the induction of histone hyperacetylation. We
      sought to determine the effects of a variety of the SCFA on colon carcinoma cell
      growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21
      deleted) cells were treated with physiologically relevant concentrations of
      various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel
      electrophoresis and immunoblotting. Growth and apoptotic effects were studied by
      flow cytometry, and differentiation effects were assessed using transient
      transfections and Northern blotting. Propionate (C3) and valerate (C5) caused
      growth arrest and differentiation in human colon carcinoma cells. The magnitude
      of their effects was associated with a lesser degree of histone hyperacetylation
      compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not
      cause histone hyperacetylation and also had no appreciable effects on cell growth
      or differentiation. SCFA-induced transactivation of the differentiation marker
      gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase
      (HDAC), further supporting the critical link between SCFA and histones. Butyrate
      also significantly increased apoptosis, whereas the other SCFA studied did not.
      The growth arrest induced by the SCFA was characterized by an increase in the
      expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1
      (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate
      of proliferation. These data suggest that the antiproliferative, apoptotic and
      differentiating properties of the various SCFA are linked to the degree of
      induced histone hyperacetylation. Furthermore, SCFA-mediated growth arrest in
      colon carcinoma cells requires the p21 gene.

PMID- 11983831
TI  - Dietary copper affects azoxymethane-induced intestinal tumor formation and
      protein kinase C isozyme protein and mRNA expression in colon of rats.
AB  - Previous studies have show that changes in protein kinase C (PKC) isoform
      expression may be related to increased susceptibility of copper-deficient rats to
      aberrant crypt formation. The purpose of this study was to determine whether
      dietary copper would affect azoxymethane-induced intestinal tumor formation and
      PKC isozyme expression in normal colonic mucosa and tumor samples. Eighty
      weanling Fischer-344 rats were randomly assigned to diets that contained either
      0.8 or 5.3 microg Cu/g diet. After 24 and 31 d of diet consumption, 30 rats/diet
      were administered azoxymethane (15 mg/kg i.p.) and 10 rats/diet were administered
      saline. Rats continued to consume their respective diets for an additional 38 wk.
      Rats injected with azoxymethane and fed the low copper diet had a significantly
      (P < 0.0001) greater small intestinal and total tumor incidence compared with
      rats fed adequate dietary copper. However, dietary copper did not affect colon
      tumor incidence. Low dietary copper significantly (P < 0.004) decreased PKC alpha
      protein expression in normal but not in tumor tissue. In contrast, low dietary
      copper did not affect PKC delta or zeta protein expression in either the normal
      or tumor tissue. PKC alpha and delta protein and mRNA expression were lower in
      tumor tissue than in normal tissue. These results along with previous
      observations suggest that dietary copper-mediated changes in PKC alpha, delta and
      zeta protein expression are not as important for colon tumor
      promotion/progression as they are for tumor initiation.

PMID- 11983832
TI  - Large particles increase viscosity and yield stress of pig cecal contents without
      changing basic viscoelastic properties.
AB  - The viscosity of gut contents should influence digestion and absorption. Earlier
      investigators measured the viscosity of intestinal contents after the removal of
      solid particles. However, we previously found that removal of solid particles
      from pig cecal contents dramatically lowered the viscosity of the contents.
      Accordingly, we examined the contribution of large solid particles to
      viscoelastic parameters of gut contents in the present study. We removed large
      particles from pig cecal contents by filtration through surgical gauze. Then, we
      reconstructed the cecal contents by returning all, one half or none of the
      original amount of the large particles to the filtrate. We measured the
      viscosity, shear stress and shear rate of these reconstructed cecal contents
      using a tube-flow viscometer. The coefficient of viscosity was larger when the
      large-particle content was higher (P < 0.01). Cecal contents behaved as a non
      Newtonian fluid and showed an apparent Bingham plastic nature irrespective of
      large-particle content. We calculated the yield stress of these fluids assuming
      that the fluids behave as Bingham plastic. The yield stress of the cecal contents
      was greater (P < 0.05) when the large-particle content was higher. The above
      results indicated that large particles elevated the viscosity and yield stress of
      gut contents without changing their basic viscoelastic character. Integrating the
      present and our previous results, we conclude that it is likely that finer
      particles such as bacteria should provide non-Newtonian and apparent Bingham
      plastic characteristics to pig cecal contents.

PMID- 11983833
TI  - Characterization of diet-dependent metabolic serotypes: proof of principle in
      female and male rats.
AB  - Our research seeks to identify a serum profile, or serotype, that reflects
      substantial changes in food intake. Earlier studies demonstrated that a number of
      low-molecular-weight, redox-active compounds of metabolome were sufficiently
      stable analytically and biologically to identify biomarkers of dietary
      restriction (DR, restriction of total food intake) in rats. A second initial
      requirement is to demonstrate feasibility, i.e., that concentration changes in
      selected serum metabolites can contain sufficient information to classify rats by
      diet. The current study distinguished 101 (female) and 112 (male)
      chromatographically identifiable compounds that differ between ad libitum (AL)
      consumption and DR 6-mo-old rats. In a cohort of female rats, both hierarchical
      cluster analysis (HCA) and principal component analyses (PCA) could distinguish
      dietary groups with 100% efficiency (101 metabolites). Repeating the
      classification studies using the 63 biologically and analytically most robust
      metabolites decreased noise without affecting categorical separation. In a cohort
      of male rats, PCA, but not HCA, distinguished the original dietary groups with
      100% accuracy (112 metabolites). A subset of 52 of the 112 metabolites enabled
      both HCA and PCA to group the male rats with 100% accuracy. These data
      demonstrate that quantitative analysis of selected serum metabolites can yield
      sufficient information by which to classify the dietary intake of a group of
      rats, identify such markers chromatographically and set the stage for validation
      of these metabolic serotypes in independent datasets.

PMID- 11983834
TI  - Characterization of diet-dependent metabolic serotypes: primary validation of
      male and female serotypes in independent cohorts of rats.
AB  - Our research seeks to identify serum profiles, or serotypes, that reflect
      substantial changes in food intake in both male and female rats. This report
      validates previously defined subsets of redox-active low-molecular-weight
      metabolites using independent cohorts of ad libitum consumption (AL) and energy
      or dietary restricted (DR) 6-mo-old male and female rats. In the male study, both
      hierarchical cluster analysis (HCA) and principal component analysis (PCA)
      distinguished the dietary groups of origin in the second male cohort with >85%
      accuracy using 56 analytically and biologically valid metabolites. Further
      analysis revealed that 29 metabolites (nine previously unidentified metabolites +
      20 chosen from the 56 metabolites) enabled HCA to distinguish dietary groups at
      100% efficacy. In the female study, the 63 previously identified serum
      metabolites were sufficiently robust to enable classification of the dietary
      intake of two female cohorts (cohorts 2 and 3) that were independent of the
      cohort on which these markers were initially identified (cohort 1).
      Classification accuracy was 94 and 100% using HCA and PCA, respectively, in the
      female cohort 2. HCA and PCA revealed that the 63-metabolite profile
      distinguished AL and DR samples at 91 and 100% accuracy in the female cohort 3,
      establishing the 63-metabolite dataset as our baseline profile. These studies
      used independent cohorts to validate and potentially improve upon previously
      defined metabolic serotype in male and female rats and set the stage for pattern
      recognition-based approaches to establish metabolome-based categorical
      separations.

PMID- 11983835
TI  - Protection against cancer by energy restriction: all experimental approaches are
      not equal.

PMID- 11983836
TI  - Modified food guide pyramid for lactovegetarians and vegans.

PMID- 11983840
TI  - The scientific evidence for a beneficial health relationship between walnuts and
      coronary heart disease.
AB  - The author and four independent experts evaluated the intent and quality of
      scientific evidence for a potential beneficial health relationship between the
      intake of walnuts and the reduction and prevention of coronary heart disease. The
      report also addresses the supporting evidence for the health benefit of other
      tree nuts and selected legumes. Compared to most other nuts, which contain
      monounsaturated fatty acids, walnuts are unique because they are rich in n-6
      (linoleate) and n-3 (linolenate) polyunsaturated fatty acids. Walnuts contain
      multiple health-beneficial components, such as having a low lysine:arginine ratio
      and high levels of arginine, folate, fiber, tannins, and polyphenols. Though
      walnuts are energy rich, clinical dietary intervention studies show that walnut
      consumption does not cause a net gain in body weight when eaten as a replacement
      food. Five controlled, peer-reviewed, human clinical walnut intervention trials,
      involving approximately 200 subjects representative of the 51% of the adult
      population in the United States at risk of coronary heart disease were reviewed.
      The intervention trials consistently demonstrated walnuts as part of a heart
      healthy diet, lower blood cholesterol concentrations. None of these studies were
      of extended duration that would be essential for evaluation of the sustainability
      of the observed outcomes. These results were supported by several large
      prospective observational studies in humans, all demonstrating a dose response
      related inverse association of the relative risk of coronary heart disease with
      the frequent daily consumption of small amounts of nuts, including walnuts.

PMID- 11983842
TI  - Mercury and dentists.

PMID- 11983843
TI  - Health and neuropsychological functioning of dentists exposed to mercury.
AB  - OBJECTIVES: A cross sectional survey of dentists in the west of Scotland and
      unmatched controls was conducted to find the effect of chronic exposure to
      mercury on health and cognitive functioning. METHODS: 180 dentists were asked to
      complete a questionnaire that included items on handling of amalgam, symptoms
      experienced, possible influences on psychomotor function, and the 12 item general
      health questionnaire. Dentists were asked to complete a dental chart of their own
      mouths and to give samples of urine, hair, and nails for mercury analysis.
      Environmental measurements of mercury in dentists' surgeries were made and
      participants undertook a package of computerised psychomotor tests. 180 control
      subjects underwent a similar procedure, completing a questionnaire, having their
      amalgam surfaces counted, giving urine, hair, and nail samples and undergoing the
      psychomotor test package. RESULTS: Dentists had, on average, urinary mercury
      concentrations over four times that of control subjects, but all but one dentist
      had urinary mercury below the Health and Safety Executive health guidance value.
      Dentists were significantly more likely than control subjects to have had
      disorders of the kidney and memory disturbance. These symptoms were not
      significantly associated with urinary mercury concentration. Differences were
      found between the psychomotor performance of dentists and controls after
      adjusting for age and sex, but there was no significant association between
      changes in psychomotor response and mercury concentrations in urine, hair, or
      nails. CONCLUSIONS: Several differences in health and cognitive functioning
      between dentists and controls were found. These differences could not be directly
      attributed to their exposure to mercury. However, as similar health effects are
      known to be associated with mercury exposure, it would be appropriate to consider
      a system of health surveillance of dental staff with particular emphasis on
      symptoms associated with mercury toxicity where there is evidence of high levels
      of exposure to environmental mercury.

PMID- 11983844
TI  - Effects of air pollution on general practitioner consultations for upper
      respiratory diseases in London.
AB  - OBJECTIVES: Few published studies have examined the effect of air pollution on
      upper respiratory conditions. Furthermore, most epidemiological studies on air
      pollution focus on mortality or hospital admissions as the main health outcomes,
      but very rarely consider the effect in primary care. If pollution effects do
      exist then the public health impact could be considerable because of the many
      patient contacts involved. We investigated the relation between air pollution and
      upper respiratory disease as reflected in number of consultations made at family
      practices in London. METHODS: The study used non-parametric methods of analysis
      of time series data, adjusting for seasonal factors, day of the week, holiday
      effects, influenza, weather, pollen concentrations, and serial correlation.
      RESULTS: It was estimated that a 10-90th percentile change (13-31 microg/m(3)) in
      sulphur dioxide (SO(2)) measures resulted in a small increase in numbers of
      childhood consultation: 3.5% (95% confidence interval (95% CI 1.4% to 5.8%).
      Stronger associations were found in the case of a 10-90th percentile change (16
      47 microg/m(3)) in fine particles (PM(10)) in adults aged 15-64 5.7% (2.9% to
      8.6%), and in adults aged 65 and over: 10.2% (5.3% to 15.3%). In general,
      associations were strongest in elderly people, weakest in the children, and were
      largely found in the winter months for these two age groups, and in the summer
      months for adults aged 15-64. An apparent decrease in consultations was
      associated with ozone concentrations but this was most pronounced in colder
      months when ozone concentrations were at their lowest. CONCLUSIONS: The results
      suggest an adverse effect of air pollution on consultations for upper respiratory
      symptoms, in particular in the case of PM(10) and SO(2). The effects are
      relatively small; however, due to the many consultations made in primary care,
      the impact on demand for services could be considerable.

PMID- 11983845
TI  - The EMECAM project: a multicentre study on air pollution and mortality in Spain:
      combined results for particulates and for sulfur dioxide.
AB  - OBJECTIVE: The EMECAM study is a collaborative effort to evaluate the impact of
      air pollution on mortality in Spain. In this paper the combined results are
      presented for the short term effects of particulates and sulfur dioxide on both
      daily mortality for all and for specific causes. METHODS: The relation between
      daily mortality for all causes, cardiovascular diseases, and respiratory
      diseases, and air pollution for particulates (daily concentrations) and SO(2) (24
      and 1 hour concentrations) was assessed in 13 Spanish cities for the period 1990
      6. With a standardised method, magnitude of association in each city was
      estimated by Poisson regression in a generalised additive model. Local estimates
      were obtained from both single and two pollutant analyses. Lastly, combined
      estimates for each cause and pollutant were obtained. RESULTS: For combined
      results, in single pollutant models a 10 microg/m(3) increase in the
      concentration of the mean of the concurrent and one day lag for black smoke was
      associated with a 0.8% (95% confidence interval (95% CI) 0.4 to 1.1%) increase in
      total mortality. The estimates for total suspended particles (TSPs) and
      particulate matter of aerodynamic diameter <10 microm (PM(10)) and total
      mortality were slightly lower. The same increase in concentrations of SO(2) was
      associated with a 0.5% increase in daily deaths. For groups of specific causes,
      higher estimations were found, specially for respiratory conditions. Peak
      concentrations of SO(2) showed significant associations with the three groups of
      mortality. When two pollutant analyses were performed, estimates for
      particulates, specially for black smoke, did not substantially change. The
      estimates for daily concentrations of SO(2) were greatly reduced, but, on the
      contrary, the association with peak concentrations of SO(2) did not show any
      change. CONCLUSIONS: There is an association between mortality and pollution
      through particulates among city populations in Spain. Peak rather than daily
      concentrations of SO(2) were related to mortality. Results suggest that
      populations in Spanish cities are exposed to health risks derived from air
      pollution.

PMID- 11983846
TI  - International business travel: impact on families and travellers.
AB  - OBJECTIVES: Spouses and staff of the World Bank Group (WBG) were questioned about
      the impact of international business travel on families and travellers. Dependent
      variables were self reported stress, concern about the health of the traveller,
      and negative impact on the family. We hypothesised that several travel factors
      (independent variables) would be associated with these impacts. These travel
      factors had to do with the frequency, duration, and predictability of travel and
      its interference with family activities. METHODS: Survey forms were developed and
      distributed to all spouses of travelling staff as well as a small sample of
      operational staff. Kendall's tau b correlation coefficients of response
      frequencies were computed with the data from scaled items. Written responses to
      open ended questions were categorised. RESULTS: Response rates for spouses and
      staff were 24% and 36%, respectively. Half the spouse sample (n=533) and almost
      75% of the staff sample (n=102) reported high or very high stress due to business
      travel. Self reported spouse stress was associated with six out of eight travel
      factors. Female spouses, those with children, and younger spouses reported
      greater stress. Self reported staff stress was significantly associated with four
      out of nine travel factors. Further insight into how business travel affects
      families and staff (including children's behavioural changes) and how families
      cope was gained through responses to written questions. CONCLUSIONS: The findings
      support the notion that lengthy and frequent travel and frequent changes in
      travel dates which affect family plans, all characteristic of WBG missions,
      negatively affects many spouses and children (particularly young children) and
      that the strain on families contributes significantly to the stress staff feel
      about their travel. Policies or management practices that take into consideration
      family activities and give staff greater leeway in controlling and refusing
      travel may help relieve stress.

PMID- 11983847
TI  - High physical work load and low job satisfaction increase the risk of sickness
      absence due to low back pain: results of a prospective cohort study.
AB  - OBJECTIVE: To determine whether physical and psychosocial load at work influence
      sickness absence due to low back pain. METHODS: The research was a part of the
      study on musculoskeletal disorders, absenteeism, stress, and health (SMASH), a 3
      year prospective cohort study on risk factors for musculoskeletal disorders.
      Workers from 21 companies located throughout The Netherlands participated in the
      part of this study on sickness absence due to low back pain. The study population
      consisted of 732 workers with no sickness absences of 3 days or longer due to low
      back pain in the 3 months before the baseline survey and complete data on the
      reasons for absences during the follow up period. The mean (range) period of
      follow up in this group was 37 (7-44) months. Physical load at work was assessed
      by analyses of video recordings. Baseline information on psychosocial work
      characteristics was obtained by a questionnaire. Data on sickness absence were
      collected from company records. The main outcome measure was the rate of sickness
      absences of 3 days or longer due to low back pain during the follow up period.
      RESULTS: After adjustment of the work related physical and psychosocial factors
      for each other and for other potential determinants, significant rate ratios
      ranging from 2.0 to 3.2 were found for trunk flexion, trunk rotation, lifting,
      and low job satisfaction. A dose-response relation was found for trunk flexion,
      but not for trunk rotation or lifting. Non-significant rate ratios of about 1.4
      were found for low supervisor support and low coworker support. Quantitative job
      demands, conflicting demands, decision authority, and skill discretion showed no
      relation with sickness absence due to low back pain. CONCLUSIONS: Flexion and
      rotation of the trunk, lifting, and low job satisfaction are risk factors for
      sickness absence due to low back pain. Some indications of a relation between low
      social support, either from supervisors or coworkers, and sickness absence due to
      low back pain are also present.

PMID- 11983848
TI  - Stomach cancer and occupation in Sweden: 1971-89.
AB  - OBJECTIVES: To examine the relation between gastric cancer and occupation among
      men and women gainfully employed in 1970 in Sweden for the period 1971-89 and,
      more specifically, to evaluate whether any excess of incidence of gastric cancer
      had also occurred among the subcohort of people reporting the same occupation in
      1960 and 1970. METHODS: In both sexes and cohorts, relative risks adjusted for
      age, period of diagnosis, and geographical risk area were computed for
      occupational codes specified at one, two, or three level (occupational sector,
      occupational group, and occupation, respectively). Relative risks were calculated
      with all other occupations as reference and then, to take socioeconomic status
      into account, solely other occupations within the same occupational sector were
      used. RESULTS: Among men, occupations with increased risk included miners and
      quarrymen, construction and metal processing workers, supporting the possible
      causative role of dusty environments in stomach cancer. In men, the results also
      provide support for increased risks among electrical and mechanical engineers,
      fishermen, petrol station workers, motor vehicle drivers, butchers and meat
      preparers, dockers, freight handlers, launderers and dry cleaners. Furthermore,
      it is worth noting interesting results for women, whose occupational risks have
      been studied less. Excess risks were found for practical nurses, cashiers, bank
      employees, engineering and electronic industry workers, food industry,
      housekeeping and cleaning workers. Due to the many occupations studied, several
      significant associations may be expected by chance. CONCLUSIONS: The study is
      explorative but provides support for the relations suggested previously between
      occupational exposure to dusty environments and stomach cancer, together with
      some new high risk occupations which should be further studied.

PMID- 11983850
TI  - Respiratory symptoms, lung function, and nasal cellularity in Indonesian wood
      workers: a dose-response analysis.
AB  - OBJECTIVES: It was hypothesised that inflammation plays a dominant part in the
      respiratory effects of exposure to wood dust. The purpose of this study was to
      relate the nasal inflammatory responses of workers exposed to meranti wood dust
      to (a) levels of exposure, (b) respiratory symptoms and (c) respiratory function.
      METHODS: A cross sectional study was carried out in 1997 in a woodworking plant
      that used mainly meranti, among 982 workers exposed to different concentrations
      of wood dust. Personal sampling (n=243) of inhalable dust measurements indicated
      mean exposure in specific jobs, and enabled classification of 930 workers in
      three exposure classes (<2, 2-5, and >5 mg/m(3)) based on job title.
      Questionnaires were used to screen respiratory symptoms in the entire population.
      Lung function was measured with two different techniques, conventional flow
      volume curves and the forced oscillation technique. Nasal lavage was done to
      assess inflammation in the upper respiratory tract. RESULTS: A negative trend
      between years of employment and most flow-volume variables was found in men, but
      not in women workers. Current exposure, however, was not related to spirometric
      outcomes, respiratory symptoms, or nasal cellularity. Some impedance variables
      were related to current exposure but also with better function at higher
      exposure. CONCLUSIONS: Exposure to meranti wood dust did not cause an
      inflammation in the upper respiratory tract nor an increase of respiratory
      symptoms or decrease of lung function. These data do not corroborate the
      hypothesis that inflammation plays a part in airway obstruction induced by wood
      dust.

PMID- 11983851
TI  - Non-malignant mortality among Norwegian silicon carbide smelter workers.
AB  - OBJECTIVES: To investigate associations between exposures in the silicon carbide
      (SiC) industry and mortality from non-malignant diseases. METHODS: Mortality
      among 2562 men, working in one of three silicon carbide smelters was
      investigated, giving 52,618 person-years of follow up from 1962 to 1996. Dose
      response relations were investigated by internal comparisons using Poisson
      regression and by stratified standardised mortality ratio (SMR) analyses.
      RESULTS: Mortality from all causes was significantly raised compared with the
      Norwegian mortalities among men, SMR=1.12, (95% confidence interval (95% CI) 1.05
      to 1.20). An excess mortality from asthma, emphysema, and chronic bronchitis
      combined was found, SMR=2.21 (95% CI 1.61 to 2.95), increasing from 1.05 in the
      unexposed category to 2.64 (95% CI 1.44 to 4.43) in the upper category of
      exposure to total dust. The Poisson regression analysis confirmed the results
      from the stratified SMR analyses, and suggested that smoking did not act as a
      confounder. No association was found for circulatory mortality. CONCLUSIONS:
      There was an increased mortality from asthma, emphysema, and chronic bronchitis
      combined among SiC workers exposed to dust.

PMID- 11983852
TI  - Design of measurement strategies for workplace exposures.

PMID- 11983853
TI  - Drying-induced hydrophobic polymer collapse.
AB  - We have used computer simulation to study the collapse of a hydrophobic chain in
      water. We find that the mechanism of collapse is much like that of a first-order
      phase transition. The evaporation of water in the vicinity of the polymer
      provides the driving force for collapse, and the rate limiting step is the
      nucleation of a sufficiently large vapor bubble. The study is made possible
      through the application of transition path sampling and a coarse-grained
      treatment of liquid water. Relevance of our findings to understanding the folding
      and assembly of proteins is discussed.

PMID- 11983854
TI  - Complete pathway for protein disulfide bond formation encoded by poxviruses.
AB  - We show that three cytoplasmic thiol oxidoreductases encoded by vaccinia virus
      comprise a complete pathway for formation of disulfide bonds in intracellular
      virion membrane proteins. The pathway was defined by analyzing conditional lethal
      mutants and effects of cysteine to serine substitutions and by trapping disulfide
      bonded heterodimer intermediates for each consecutive step. The upstream
      component, E10R, belongs to the ERV1/ALR family of FAD-containing sulfhydryl
      oxidases that use oxygen as the electron acceptor. The second component, A2.5L,
      is a small alpha-helical protein with a CxxxC motif that forms a stable disulfide
      linked heterodimer with E10R and a transient disulfide-linked complex with the
      third component, G4L. The latter is a thioredoxin-like protein that directly
      oxidizes thiols of L1R, a structural component of the virion membrane with three
      stable disulfide bonds, and of the related protein F9L. These five proteins are
      conserved in all poxviruses, suggesting that the pathway is an ancestral
      mechanism for direct thiol-disulfide interchanges between proteins even in an
      unfavorable reducing environment.

PMID- 11983855
TI  - Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4
      chemokine receptor.
AB  - We investigated the role of the CXCR4 chemokine receptor in development of the
      mouse hippocampus. CXCR4 mRNA is expressed at sites of neuronal and progenitor
      cell migration in the hippocampus at late embryonic and early postnatal ages.
      mRNA for stromal cell-derived factor 1 (SDF-1), the only known ligand for the
      CXCR4 receptor, is expressed close to these migration sites, in the meninges
      investing the hippocampal primordium and the primordium itself. In mice
      engineered to lack the CXCR4 receptor, the morphology of the hippocampal dentate
      gyrus (DG) is dramatically altered. Gene expression markers for DG granule
      neurons and bromodeoxyuridine labeling of dividing cells revealed an underlying
      defect in the stream of postmitotic cells and secondary dentate progenitor cells
      that migrate toward and form the DG. In the absence of CXCR4, the number of
      dividing cells in the migratory stream and in the DG itself is reduced, and
      neurons appear to differentiate prematurely before reaching their target. Our
      findings indicate a role for the SDF-1/CXCR4 chemokine signaling system in DG
      morphogenesis. Finally, the DG is unusual as a site of adult neurogenesis. We
      find that both CXCR4 and SDF-1 are expressed in the adult DG, suggesting an
      ongoing role in DG morphogenesis.

PMID- 11983857
TI  - Collaborative signaling by mixed chemoreceptor teams in Escherichia coli.
AB  - Chemoreceptors of the methyl-accepting chemotaxis protein family form clusters,
      typically at the cell pole(s), in both Bacteria and Archaea. To elucidate the
      architecture and signaling role of receptor clusters, we investigated
      interactions between the serine (Tsr) and aspartate (Tar) chemoreceptors in
      Escherichia coli by constructing Tsr mutations at the six hydrophobic and five
      polar residues implicated in "trimer of dimers" formation. Tsr mutants with
      proline replacements could not mediate serine chemotaxis, receptor clustering, or
      clockwise flagellar rotation. Alanine and tryptophan mutants, although also
      nonchemotactic, formed receptor clusters, and some produced clockwise flagellar
      rotation, indicating receptor-coupled activation of the signaling CheA kinase.
      The alanine and tryptophan mutants evidently assemble defective receptor
      complexes that cannot modulate CheA activity in response to serine stimuli. In
      cells containing wild-type Tar receptors, tryptophan replacements in Tsr
      interfered with Tar function, whereas four Tsr mutants with alanine replacements
      regained Tsr function. These epistatic and rescuable phenotypes imply
      interactions between Tsr and Tar dimers in higher-order signaling teams. The
      bulky side chain in tryptophan mutants may prevent stimulus-induced
      conformational changes in the team, whereas the small side chain in alanine
      mutants may permit signaling control when teamed with functional receptor
      molecules. Direct physical interactions between Tsr and Tar molecules were
      observed by in vivo chemical crosslinking. Wild-type Tsr crosslinked to Tar,
      whereas a clustering-defective proline replacement mutant did not. These findings
      indicate that bacterial chemoreceptor clusters are comprised of signaling teams,
      seemingly based on trimers of dimers, that can contain different receptor types
      acting collaboratively.

PMID- 11983858
TI  - Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ
      domain protein GRIP1.
AB  - Glutamate receptor-interacting protein 1 (GRIP1) is an adaptor protein composed
      of seven PDZ (postsynaptic density-95/Discs large/zona occludens-1) domains,
      capable of mediating diverse protein-protein interactions. GRIP1 has been
      implicated in the regulation of neuronal synaptic function, but its physiologic
      roles have not been defined in vivo. We find that elimination of murine GRIP1
      results in embryonic lethality. GRIP1(-/-) embryos develop abnormalities of the
      dermo-epidermal junction, resulting in extensive skin blistering around day 12 of
      embryonic life. Ultra-structural characterization of the blisters (or bullae)
      revealed cleavage of the dermo-epidermal junction below the lamina densa, an
      alteration reminiscent of the dystrophic form of human epidermolysis bullosa.
      Blisters were also observed in the lateral ventricle of the brain and in the
      meninges covering the cerebral cortex. These genetic data suggest that the GRIP1
      scaffolding protein is required for the formation and integrity of the dermo
      epidermal junction and reveal the importance of PDZ domains in the organization
      of supramolecular structures essential for mammalian embryonic development.

PMID- 11983859
TI  - Aldosterone signaling pathway across the nuclear envelope.
AB  - We describe the route by which aldosterone-triggered macromolecules enter and
      exit the cell nucleus of Xenopus laevis oocyte. Oocytes were microinjected with
      50 fmol aldosterone and then enucleated 2-30 min after injection. After
      isolation, nuclear envelope electrical resistance (NEER) was measured in the
      intact cell nuclei by using the nuclear hourglass technique. We observed three
      NEER stages: an early peak 2 min after injection, a sustained depression after 5
      15 min, and a final late peak 20 min after injection. Because NEER reflects the
      passive electrical permeability of nuclear pores, we investigated with atomic
      force microscopy aldosterone-induced conformational changes of individual nuclear
      pore complexes (NPCs). At the early peak we observed small ( congruent with 100
      kDa) molecules (flags) attached to the NPC surface. At the sustained depression
      NPCs were found free of flags. At the late peak large ( congruent with 800 kDa)
      molecules (plugs) were detected inside the central channels. Ribonuclease or
      actinomycin D treatment prevented the late NEER peak. Coinjection of aldosterone
      (50 fmol) and its competitive inhibitor spironolactone (500 fmol) eliminated the
      electrical changes as well as flag and plug formation. We conclude: (i) The
      genomic response of aldosterone can be electrically measured in intact oocyte
      nuclei. (ii) Flags represent aldosterone receptors on their way into the cell
      nucleus whereas plugs represent ribonucleoproteins carrying aldosterone-induced
      mRNA from the nucleoplasm into the cytoplasm. (iii) Because plugs can be
      mechanically harvested with the atomic force microscopy stylus, oocytes could
      serve as a bioassay system for identifying aldosterone-induced early genes.

PMID- 11983860
TI  - Global changes in gene expression by human polymorphonuclear leukocytes during
      receptor-mediated phagocytosis: cell fate is regulated at the level of gene
      expression.
AB  - Phagocytes are a critical component of the innate immune response in humans and
      eliminate invading microorganisms through a process known as phagocytosis. Two
      distinct receptor-linked phagocytic pathways, one with Ab receptors (FcRs; FcR,
      Fc receptor) and the other complement receptors (CRs), mediate binding and
      ingestion of pathogens by human polymorphonuclear leukocytes (PMNs). Although
      progress has been made toward defining complex signal transduction processes that
      underlie phagocytosis in each pathway, very little is known about gene regulation
      during or after phagocytosis. Therefore, we used human oligonucleotide
      microarrays to identify changes in expression of 12,561 genes accompanying FcR-
      and CR-mediated phagocytosis. Eighty-four percent of 279 differentially expressed
      genes were induced or repressed 90 min after ingestion of Ab- and/or complement
      opsonized particles. Unexpectedly, more than 30 of these genes encoded proteins
      involved in at least three distinct apoptotic pathways. Ninety-four
      differentially expressed cell fate-related genes were identified between 180 and
      360 min after phagocytosis and most were induced or repressed by PMNs activated
      through both receptors simultaneously. By using flow cytometry, we found that FcR
      and CR-mediated phagocytosis each promoted programmed cell death in human PMNs;
      however, phagocytosis mediated by the combination of FcRs and CRs induced
      apoptosis earlier than that by either receptor alone. Our results reveal distinct
      patterns of receptor-mediated gene expression that define complex inducible
      apoptotic pathways in activated PMNs. Most significantly, we discovered that
      programmed cell death is regulated at the level of gene expression. Thus, we
      hypothesize that gene regulation in PMNs facilitates resolution of inflammatory
      responses.

PMID- 11983861
TI  - Key role of proline L209 in connecting the distant quinone pockets in the
      reaction center of Rhodobacter sphaeroides.
AB  - Photosynthetic bacterial reaction centers convert light excitation into chemical
      free energy. The initial electron transfer leads to the consecutive
      semireductions of the primary (Q(A)) and secondary (Q(B)) quinone acceptors. The
      Q(A)(-) and Q(B)(-) formations induce proton uptake from the bulk. Their
      magnitudes (H(+)/Q(A)(-) and H(+)/Q(B)(-), respectively) probe the electrostatic
      interactions within the complex. The pH dependence of H(+)/Q(A)(-) and H(+)/Q(B)(
      ) were studied in five single mutants modified at the L209 site (L209P-
      >F,Y,W,E,T). This residue is situated at the border of a continuous chain of
      water molecules connecting Q(B) to the bulk. In the wild type (WT), a proton
      uptake band is present at high pH in the H(+)/Q(A)(-) and H(+)/Q(B)(-) curves and
      is commonly attributed to a cluster of acidic groups situated nearby Q(B). In the
      H(+)/Q(A)(-) curves of the L209 variants, this band is systematically absent but
      remains in the H(+)/Q(B)(-) curves. Moreover, notable increase of H(+)/Q(B)(-) is
      observed in the L209 mutants at neutral pH as compared with the WT. The large
      effects observed in all L209 mutants are not associated with significant
      structural changes (Kuglstatter, A., Ermler, U., Michel, H., Baciou, L. &
      Fritzsch, G. Biochemistry (2001) 40, 4253-4260). Our data suggest that, in the
      L209 mutants, the Q(B) cluster does not respond to the Q(A)(-) formation as
      observed in the WT. We propose that, in the mutants, removal of the rigid proline
      L209 breaks a necessary hydrogen bonding connection between the quinone sites.
      These findings suggest an important role for structural rigidity in ensuring a
      functional interaction between quinone binding sites.

PMID- 11983863
TI  - The genetics of maternal care: direct and indirect genetic effects on phenotype
      in the dung beetle Onthophagus taurus.
AB  - While theoretical models of the evolution of parental care are based on the
      assumption of underlying genetic variance, surprisingly few quantitative genetic
      studies of this life-history trait exist. Estimation of the degree of genetic
      variance in parental care is important because it can be a significant source of
      maternal effects, which, if genetically based, represent indirect genetic
      effects. A major prediction of indirect genetic effect theory is that traits
      without heritable variation can evolve because of the heritable environmental
      variation that indirect genetic effects provide. In the dung beetle, Onthophagus
      taurus, females provide care to offspring by provisioning a brood mass. The size
      of the brood mass has pronounced effects on offspring phenotype. Using a half-sib
      breeding design we show that the weight of the brood mass females produce
      exhibits significant levels of additive genetic variance due to sires. However,
      variance caused by dams is considerably larger, demonstrating that maternal
      effects are also important. Body size exhibited low additive genetic variance.
      However, body size exerts a strong maternal influence on the weight of brood
      masses produced, accounting for 22% of the nongenetic variance in offspring body
      size. Maternal body size also influenced the number of offspring produced but
      there was no genetic variance for this trait. Offspring body size and brood mass
      weight exhibited positive genetic and phenotypic correlations. We conclude that
      both indirect genetic effects, via maternal care, and nongenetic maternal
      effects, via female size, play important roles in the evolution of phenotype in
      this species.

PMID- 11983862
TI  - Mutations associated with base excision repair deficiency and methylation-induced
      genotoxic stress.
AB  - The long-term effect of exposure to DNA alkylating agents is entwined with the
      cell's genetic capacity for DNA repair and appropriate DNA damage responses. A
      unique combination of environmental exposure and deficiency in these responses
      can lead to genomic instability; this "gene-environment interaction" paradigm is
      a theme for research on chronic disease etiology. In the present study, we used
      mouse embryonic fibroblasts with a gene deletion in the base excision repair
      (BER) enzymes DNA beta-polymerase (beta-pol) and alkyladenine DNA glycosylase
      (AAG), along with exposure to methyl methanesulfonate (MMS) to study mutagenesis
      as a function of a particular gene-environment interaction. The beta-pol null
      cells, defective in BER, exhibit a modest increase in spontaneous mutagenesis
      compared with wild-type cells. MMS exposure increases mutant frequency in beta
      pol null cells, but not in isogenic wild-type cells; UV light exposure or N
      methyl-N'-nitro-N-nitrosoguanidine exposure increases mutant frequency similarly
      in both cell lines. The MMS-induced increase in mutant frequency in beta-pol null
      cells appears to be caused by DNA lesions that are AAG substrates, because
      overexpression of AAG in beta-pol null cells eliminates the effect. In contrast,
      beta-pol/AAG double null cells are slightly more mutable than the beta-pol null
      cells after MMS exposure. These results illustrate that BER plays a role in
      protecting mouse embryonic fibroblast cells against methylation-induced mutations
      and characterize the effect of a particular combination of BER gene defect and
      environmental exposure.

PMID- 11983864
TI  - Molecular dynamics simulations of protein folding from the transition state.
AB  - Putative transition-state ensemble (TSE) conformations of src SH3 were identified
      by monitoring the deviation from the experimental phi values along molecular
      dynamics (MD) simulations of unfolding. Sixty MD trajectories (for a total of
      about 7 micros) were then started from the putative TSE. About one-half of the 60
      runs reached the folded state while unfolding was observed in the remaining half
      of the runs. This result validates phi-value analysis as an approach to obtain
      structural information on the transition state. It also demonstrates that an
      atomic resolution description of the TSE can be extracted from MD simulations.
      All conformations in the TSE have the central three-stranded beta-sheet formed in
      agreement with experimental data. An elongation of strand beta 2 as well as non
      native side-chain interactions between the diverging turn and the distal hairpin
      are observed. The simulation results indicate that the tight packing of the side
      chains between the diverging turn and the distal hairpin is a necessary condition
      for rapid folding. Contacts between residues in the most structured element of
      the TSE, the central beta-sheet, are kinetically more important than those
      between the N- and C-terminal strands.

PMID- 11983865
TI  - Repression of photosynthesis gene expression by formation of a disulfide bond in
      CrtJ.
AB  - Many species of purple photosynthetic bacteria repress synthesis of their
      photosystem in the presence of molecular oxygen. The bacterium Rhodobacter
      capsulatus mediates this process by repressing expression of bacteriochlorophyll,
      carotenoid, and light-harvesting genes via the aerobic repressor, CrtJ. In this
      study, we demonstrate that CrtJ forms an intramolecular disulfide bond in vitro
      and in vivo when exposed to oxygen. Mutational and sulfhydryl-specific chemical
      modification studies indicate that formation of a disulfide bond is critical for
      CrtJ binding to its target promoters. Analysis of the redox states of aerobically
      and anaerobically grown cells indicates that they have similar redox states of
      approximately -200 mV, thereby demonstrating that a change in midpoint potential
      is not responsible for disulfide bond formation. In vivo and in vitro analyses
      indicate that disulfide bond formation in CrtJ is insensitive to the addition of
      hydrogen peroxide but is sensitive to molecular oxygen. These results suggest
      that disulfide bond formation in CrtJ may differ from the mechanism of disulfide
      bond formation used by OxyR.

PMID- 11983866
TI  - ATP6S1 elicits potent humoral responses associated with immune-mediated tumor
      destruction.
AB  - An important goal of cancer immunology is the identification of antigens
      associated with tumor destruction. Vaccination with irradiated tumor cells
      engineered to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF)
      generates potent, specific, and long-lasting antitumor immunity in multiple
      murine tumor models. A phase I clinical trial of this vaccination strategy in
      patients with advanced melanoma demonstrated the consistent induction of dense
      CD4(+) and CD8(+) T lymphocyte and plasma cell infiltrates in distant metastases,
      resulting in extensive tumor destruction, fibrosis, and edema. Antimelanoma
      antibody and cytotoxic T cell responses were associated with tumor cell death. To
      characterize the targets of these responses, we screened an autologous cDNA
      expression library prepared from a densely infiltrated metastasis with
      postvaccination sera from a long-term responding patient. High-titer IgG
      antibodies detected ATP6S1, a putative accessory unit of the vacuolar H(+)-ATPase
      complex. A longitudinal analysis of this patient revealed an association between
      the vaccine-induced increase in antibodies to ATP6S1 and tumor destruction. Three
      additional vaccinated melanoma patients and three metastatic non-small cell lung
      carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells
      similarly showed a correlation between humoral responses to ATP6S1 and tumor
      destruction. Moreover, a chronic myelogenous leukemia patient who experienced a
      complete remission after CD4(+) donor lymphocyte infusions also developed high
      titer antibodies to ATP6S1. Lastly, vaccination with GM-CSF-secreting B16
      melanoma cells stimulated high-titer antibodies to ATPS1 in a murine model. Taken
      together, these findings demonstrate that potent humoral responses to ATP6S1 are
      associated with immune-mediated destruction of diverse tumors.

PMID- 11983867
TI  - Dynamic assembly of MinD on phospholipid vesicles regulated by ATP and MinE.
AB  - Selection of the division site in Escherichia coli is regulated by the min system
      and requires the rapid oscillation of MinD between the two halves of the cell
      under the control of MinE. In this study we have further investigated the
      molecular basis for this oscillation by examining the interaction of MinD with
      phospholipid vesicles. We found that MinD bound to phospholipid vesicles in the
      presence of ATP and, upon binding, assembled into a well-ordered helical array
      that deformed the vesicles into tubes. Stimulation of the MinD ATPase by addition
      of MinE led to disassembly of the tubes and the release of MinD from the
      vesicles. It is proposed that this MinE-regulated dynamic assembly of MinD
      underlies MinD oscillation.

PMID- 11983868
TI  - Selection bias in gene extraction on the basis of microarray gene-expression
      data.
AB  - In the context of cancer diagnosis and treatment, we consider the problem of
      constructing an accurate prediction rule on the basis of a relatively small
      number of tumor tissue samples of known type containing the expression data on
      very many (possibly thousands) genes. Recently, results have been presented in
      the literature suggesting that it is possible to construct a prediction rule from
      only a few genes such that it has a negligible prediction error rate. However, in
      these results the test error or the leave-one-out cross-validated error is
      calculated without allowance for the selection bias. There is no allowance
      because the rule is either tested on tissue samples that were used in the first
      instance to select the genes being used in the rule or because the cross
      validation of the rule is not external to the selection process; that is, gene
      selection is not performed in training the rule at each stage of the cross
      validation process. We describe how in practice the selection bias can be
      assessed and corrected for by either performing a cross-validation or applying
      the bootstrap external to the selection process. We recommend using 10-fold
      rather than leave-one-out cross-validation, and concerning the bootstrap, we
      suggest using the so-called .632+ bootstrap error estimate designed to handle
      overfitted prediction rules. Using two published data sets, we demonstrate that
      when correction is made for the selection bias, the cross-validated error is no
      longer zero for a subset of only a few genes.

PMID- 11983869
TI  - Base-specific fragmentation of amplified 16S rRNA genes analyzed by mass
      spectrometry: a tool for rapid bacterial identification.
AB  - A rapid approach to the 16S rRNA gene (16S rDNA)-based bacterial identification
      has been developed that combines uracil-DNA-glycosylase (UDG)-mediated base
      specific fragmentation of PCR products with matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOF MS). 16S rDNA signature
      sequences were PCR-amplified from both cultured and as-yet-uncultured bacteria in
      the presence of dUTP instead of dTTP. These PCR products then were immobilized
      onto a streptavidin-coated solid support to selectively generate either sense or
      antisense templates. Single-stranded amplicons were subsequently treated with
      uracil-DNA-glycosylase to generate T-specific abasic sites and fragmented by
      alkaline treatment. The resulting fragment patterns were analyzed by MALDI-TOF
      MS. Mass signals of 16S rDNA fragments were compared with patterns calculated
      from published 16S rDNA sequences. MS of base-specific fragments of amplified 16S
      rDNA allows reliable discrimination of sequences differing by only one
      nucleotide. This approach is fast and has the potential for high-throughput
      identification as required in clinical, pharmaceutical, or environmental
      microbiology. In contrast to identification by MS of intact whole bacterial
      cells, this technique allows for the characterization of both cultured and as-yet
      uncultured bacteria.

PMID- 11983870
TI  - Laurasian migration explains Gondwanan disjunctions: evidence from Malpighiaceae.
AB  - Explanations for biogeographic disjunctions involving South America and Africa
      typically invoke vicariance of western Gondwanan biotas or long distance
      dispersal. These hypotheses are problematical because many groups originated and
      diversified well after the last known connection between Africa and South America
      (approximately 105 million years ago), and it is unlikely that "sweepstakes"
      dispersal accounts for many of these disjunctions. Phylogenetic analyses of the
      angiosperm clade Malpighiaceae, combined with fossil evidence and molecular
      divergence-time estimates, suggest an alternative hypothesis to account for such
      distributions. We propose that Malpighiaceae originated in northern South
      America, and that members of several clades repeatedly migrated into North
      America and subsequently moved via North Atlantic land connections into the Old
      World during episodes starting in the Eocene, when climates supported tropical
      forests. This Laurasian migration route may explain many other extant lineages
      that exhibit western Gondwanan distributions.

PMID- 11983871
TI  - The OhrR repressor senses organic hydroperoxides by reversible formation of a
      cysteine-sulfenic acid derivative.
AB  - Reactive oxygen species induce the expression of detoxification and repair genes
      critical for life in an aerobic environment. Bacterial factors that sense
      reactive oxygen species use either thiol-disulfide exchange reactions (OxyR,
      RsrA) or redox labile 2Fe-2S clusters (SoxR). We demonstrate that the reduced
      form of Bacillus subtilis OhrR binds cooperatively to two adjacent inverted
      repeat sequences in the ohrA control region and thereby represses transcription.
      In the presence of organic hydroperoxides, OhrR is inactivated by the reversible
      oxidation of a single conserved cysteine residue to the corresponding cysteine
      sulfenic acid, and perhaps to higher oxidation states.

PMID- 11983872
TI  - beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility,
      and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous
      wounds.
AB  - Fibroproliferative processes are a group of disorders in which there is excessive
      proliferation of spindle (mesenchymal fibroblast-like) cells. They range from
      hypertrophic scars to neoplasms such as aggressive fibromatosis. Cells from these
      disorders share cytologic similarity with fibroblasts present during the
      proliferative phase of wound healing, suggesting that they represent a prolonged
      wounding response. A critical role for beta-catenin in mesenchymal cells in
      fibroproliferative processes is suggested by its high rate of somatic mutation in
      aggressive fibromatosis. Using a Tcf-reporter mouse we found that beta-catenin
      protein level and Tcf-transcriptional activity are elevated in fibroblasts during
      the proliferative phase of healing. We generated a transgenic mouse in which
      stabilized beta-catenin is expressed in mesenchymal cells under control of a
      tetracycline-regulated promoter. Fibroblasts from the transgenic mice exhibited
      increased proliferation, motility, and invasiveness when expressing stabilized
      beta-catenin and induced tumors after induction of the transgene when grafted
      into nude mice. Mice developed aggressive fibromatoses and hyperplastic
      gastrointestinal polyps after 3 months of transgene induction and healed with
      hyperplastic cutaneous wounds compared with control mice, which demonstrates an
      important function for beta-catenin in mesenchymal cells and shows a central role
      for beta-catenin in wound healing and fibroproliferative disorders.

PMID- 11983873
TI  - Iris hypoplasia in mice that lack the alternatively spliced Pax6(5a) isoform.
AB  - PAX6 is an evolutionarily conserved transcription factor that plays a critical
      role in vertebrate and invertebrate eye formation. Heterozygous null mutations in
      the PAX6 gene result in aniridia in humans and a distinct small eye syndrome in
      rodents. Vertebrates primarily express two alternatively spliced isoforms of Pax6
      that differ by the presence or absence of exon 5a (e5A) that encodes an
      additional 14 aa residues within the paired domain. The e5a-containing isoform,
      PAX6(5a), is specific to and conserved in vertebrates. To determine the role of
      PAX6(5a), we have generated mice that lack e5a of the Pax6 gene. Unlike Pax6 null
      mice that exhibit anopthalmia with central nervous system defects and lethality,
      5a isoform-null mice have iris hypoplasia and defects in the cornea, lens, and
      retina. Although invertebrates have structures that respond to light intensity
      and act to restrict light exposure of the eyes, a significant and distinct
      feature of the vertebrate eye is its ability to regulate the amount of incoming
      light through contractile pupils. This feature of the eye not only allows
      vertebrates to see in various light conditions but also enhances image
      resolution. The requirement of the 5a isoform in iris formation suggests that the
      evolution of this isoform contributed to advanced features of the vertebrate eye.

PMID- 11983874
TI  - Antibiotics in agriculture: when is it time to close the barn door?

PMID- 11983875
TI  - Unraveling the genetics and mechanisms of cardiac arrhythmia.

PMID- 11983876
TI  - Disentangling the MYC web.

PMID- 11983877
TI  - Brain-directed gene therapy for lysosomal storage disease: going well beyond the
      blood- brain barrier.

PMID- 11983878
TI  - Finding the crosswalks on DNA.

PMID- 11983883
TI  - The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole
      dimers: structure, quantum-theoretical analysis, and simultaneity principles.
AB  - Six stable dimer models for 7-azaindole (including the classic C(2h) doubly
      hydrogen-bonded, coplanar, centrosymmetric dimer) are considered to be observable
      in adiabatic nozzle jet molecular beams. They are analyzed by hybrid density
      functional theory (DFT), the MP2 ab initio method for the ground electronic
      state, and the single-excitation configuration interaction (CIS) (over frozen
      ground state optimized geometries obtained from DFT) excited state calculations,
      for global potential minima and proton-transfer potential energy curves. Three
      simultaneity principles are stated: (i) intermolecular coherent excitation
      molecular exciton simultaneity, (ii) intramolecular acid-base change simultaneity
      at the pyrrolo-N-H and aza-N proton-donor, proton-acceptor sites, and (iii)
      intermolecular simultaneity of catalytic proton-donor, proton-acceptor action. It
      is suggested that the formation of the classic C(2h) dimer of 7-azaindole, which
      is considered exclusively by previous researchers, can be formed from at least
      one of the several card-pack hydrogen-bonded dimers in a secondary slower step
      approaching a microsecond scale, instead of the picosecond events at the
      supersonic nozzle. It is proposed that the complexity of dimerization modes is
      the basis of the postexcitation, postionization diverse kinetic isotope results.

PMID- 11983884
TI  - The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole
      dimers: a model for the secondary evolution of the classic C2h dimer and
      comparison of four mechanisms.
AB  - A mechanism is proposed for the formation in gas phase, during a short time, of
      the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly
      hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry
      structures most likely to be formed in the supersonic jet expansion molecular
      beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer
      with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown
      to be capable of unhinging about the hydrogen-bond pair as an axis, from 0
      degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h)
      structure with its delicate geometry and symmetry. This relaxation mechanism is
      feasible in the 3-micros interval between the nozzle escape and the first laser
      pulse interception of the molecular beam. In the second part of the paper four
      published mechanisms are compared for concerted vs. two-step biprotonic
      phototransfer for the 7AI dimers. The dependence of the latter two models on H
      atom instead of proton-transfer as an intermediate step negates the mechanism in
      a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron
      orbital that would be generated. The concerted mechanism for biprotonic
      phototransfer is reaffirmed by the analysis of the quantum mechanical conditions
      set on the biprotonic transfer in the photo-excited molecular 7AI pair.

PMID- 11983885
TI  - Determination of causal connectivities of species in reaction networks.
AB  - We present an approach to the determination of causal connectivities and part of
      the kinetics of complex reaction systems. Our approach is based on analytical and
      computational methods for studying the effects of a pulse change of concentration
      of a chemical species in a reaction network, either at equilibrium or in a
      nonequilibrium stationary state. Such disturbances generally propagate through a
      few species, depending on the values of the kinetic coefficients, before being
      broadened and dissipated. This short range gives a local probe of the kinetics
      and connectivity of the reaction network. The range of propagation also indicates
      species to perturb in further experiments. From piecing together these local
      connectivities, the global structure of the network can be constructed. The
      experimental design allows deduction of both reaction orders and rate constants
      in many cases. An example of the usefulness of the approach is illustrated on a
      model of a part of glycolysis.

PMID- 11983886
TI  - Loss of the membrane anchor of the target receptor is a mechanism of
      bioinsecticide resistance.
AB  - The mosquitocidal activity of Bacillus sphaericus is because of a binary toxin
      (Bin), which binds to Culex pipiens maltase 1 (Cpm1), an alpha-glucosidase
      present in the midgut of Culex pipiens larvae. In this work, we studied the
      molecular basis of the resistance to Bin developed by a strain (GEO) of C.
      pipiens. Immunohistochemical and in situ hybridization experiments showed that
      Cpm1 was undetectable in the midgut of GEO larvae, although the gene was
      correctly transcribed. The sequence of the cpm1(GEO) cDNA differs from the
      sequence we previously reported for a susceptible strain (cpm1(IP)) by seven
      mutations: six missense mutations and a mutation leading to the premature
      termination of translation. When produced in insect cells, Cpm1(IP) was attached
      to the membrane by a glycosylphosphatidylinositol (GPI). In contrast, the
      premature termination of translation of Cpm1(GEO) resulted in the targeting of
      the protein to the extracellular compartment because of truncation of the GPI
      anchoring site. The interaction between Bin and Cpm1(GEO) and the enzyme activity
      of the receptor were not affected. Thus, Bin is not toxic to GEO larvae because
      it cannot interact with the midgut cell membrane, even though its receptor site
      is unaffected. This mechanism contrasts with other known resistance mechanisms in
      which point mutations decrease the affinity of binding between the receptor and
      the toxin.

PMID- 11983887
TI  - The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho
      D-arabinonohydroxamic acid.
AB  - Phosphoglucose isomerase (EC ) catalyzes the second step in glycolysis, the
      reversible isomerization of D-glucose 6-phosphate to D-fructose 6-phosphate. The
      reaction mechanism involves acid-base catalysis with proton transfer and proceeds
      through a cis-enediol(ate) intermediate. 5-Phospho-D-arabinonohydroxamic acid
      (5PAH) is a synthetic small molecule that resembles the reaction intermediate,
      differing only in that it has a nitrogen atom in place of C1. Hence, 5PAH is the
      best inhibitor of the isomerization reaction reported to date with a K(i) of 2 x
      10(-7) M. Here we report the crystal structure of rabbit phosphoglucose isomerase
      complexed with 5PAH at 1.9 A resolution. The interaction of 5PAH with amino acid
      residues in the enzyme active site supports a model of the catalytic mechanism in
      which Glu-357 transfers a proton between C1 and C2 and Arg-272 helps stabilize
      the intermediate. It also suggests a mechanism for proton transfer between O1 and
      O2.

PMID- 11983888
TI  - Solution structures of the cytoplasmic tail complex from platelet integrin alpha
      IIb- and beta 3-subunits.
AB  - Integrin adhesion receptors constitute a cell-signaling system whereby
      interactions in the small cytoplasmic domains of the heterodimeric alpha- and
      beta-subunits provoke major functional alterations in the large extracellular
      domains. With two-dimensional NMR spectroscopy, we examined two synthetic
      peptides [alphaIIb((987)MWKVGFFKRNR) and beta3((716)KLLITIHDRKEFAKFEEERARAKWD)]
      encompassing the membrane-proximal regions of the cytoplasmic domain motifs from
      the platelet integrin complex alphaIotaIotabbeta3. These membrane-proximal
      regions contain two conserved motifs, represented by (989)KVGFFKR in the alphaIIb
      subunit, and (716)KLLITIHDR in the beta3-subunit. The dimer interaction consists
      of two adjacent helices with residues V990 and F993 of the alphaIotaIotab-subunit
      heavily implicated in the dimer interfacial region, as is I719 of beta3. These
      residues are situated within the conserved motifs of their respective proteins.
      Further structural analysis of this unique peptide heterodimer suggests that two
      distinct conformers are present. The major structural difference between the two
      conformers is a bend in the beta3-peptide between D723 and A728, whereas the
      helical character in the other regions remains intact. Earlier mutational
      analysis has shown that a salt bridge between the side chains of
      alphaIotaIotab(R955) and beta3(D723) is formed. When this ion pair was modeled
      into both conformers, increased nuclear Overhauser effect violations suggested
      that the more bent structure was less able to accommodate this interaction. These
      results provide a molecular level rationalization for previously reported
      biochemical studies, as well as a basis for an atomic level understanding of the
      intermolecular interactions that regulate integrin activity.

PMID- 11983889
TI  - Galactose metabolism is essential for the African sleeping sickness parasite
      Trypanosoma brucei.
AB  - The tsetse fly-transmitted protozoan parasite Trypanosoma brucei is the causative
      agent of human African sleeping sickness and the cattle disease Nagana. The
      bloodstream form of the parasite uses a dense cell-surface coat of variant
      surface glycoprotein to escape the innate and adaptive immune responses of the
      mammalian host and a highly glycosylated transferrin receptor to take up host
      transferrin, an essential growth factor. These glycoproteins, as well as other
      flagellar pocket, endosomal, and lysosomal glycoproteins, are known to contain
      galactose. The parasite is unable to take up galactose, suggesting that it may
      depend on the action of UDP-glucose 4'-epimerase for the conversion of UDP-Glc to
      UDP-Gal and subsequent incorporation of galactose into glycoconjugates via UDP
      Gal-dependent galactosyltransferases. In this paper, we describe the cloning of
      T. brucei galE, encoding T. brucei UDP-Glc-4'-epimerase, and functional
      characterization by complementation of a galE-deficient Escherichia coli mutant
      and enzymatic assay of recombinant protein. A tetracycline-inducible conditional
      galE null mutant of T. brucei was created using a transgenic parasite expressing
      the TETR tetracycline repressor protein gene. Withdrawal of tetracycline led to a
      cessation of cell division and substantial cell death, demonstrating that
      galactose metabolism in T. brucei proceeds via UDP-Glc-4'-epimerase and is
      essential for parasite growth. After several days without tetracycline, cultures
      spontaneously recovered. These cells were shown to have undergone a genetic
      rearrangement that deleted the TETR gene. The results show that enzymes and
      transporters involved in galactose metabolism may be considered as potential
      therapeutic targets against African trypanosomiasis.

PMID- 11983890
TI  - The identification of functional modules from the genomic association of genes.
AB  - By combining the pairwise interactions between proteins, as predicted by the
      conserved co-occurrence of their genes in operons, we obtain protein interaction
      networks. Here we study the properties of such networks to identify functional
      modules: sets of proteins that together are involved in a biological process. The
      complete network contains 3,033 orthologous groups of proteins in 38 genomes. It
      consists of one giant component, containing 1,611 orthologous groups, and of 516
      small disjointed clusters that, on average, contain only 2.7 orthologous groups.
      These small clusters have a homogeneous functional composition and thus represent
      functional modules in themselves. Analysis of the giant component reveals that it
      is a scale-free, small-world network with a high degree of local clustering (C =
      0.6). It consists of locally highly connected subclusters that are connected to
      each other by linker proteins. The linker proteins tend to have multiple
      functions, or are involved in multiple processes and have an above average
      probability of being essential. By splitting up the giant component at these
      linker proteins, we identify 265 subclusters that tend to have a homogeneous
      functional composition. The rare functional inhomogeneities in our subclusters
      reflect the mixing of different types of (molecular) functions in a single
      cellular process, exemplified by subclusters containing both metabolic enzymes as
      well as the transcription factors that regulate them. Comparative genome
      analysis, thus, allows identification of a level of functional interaction
      between that of pairwise interactions, and of the complete genome.

PMID- 11983891
TI  - Catalysis of S-nitrosothiols formation by serum albumin: the mechanism and
      implication in vascular control.
AB  - Nitric oxide (NO(.)) is a short-lived physiological messenger. Its various
      biological activities can be preserved in a more stable form of S-nitrosothiols
      (RS-NO). Here we demonstrate that at physiological NO(.) concentrations, plasma
      albumin becomes saturated with NO(.) and accelerates formation of low-molecular
      weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar
      catalysis of NO(.) oxidation in the albumin hydrophobic core and specific
      transfer of NO(+) to LMW thiols. Albumin-mediated S-nitrosylation and its
      vasodilatory effect directly depend on the concentration of circulating LMW
      thiols. Results suggest that the hydrophobic phase formed by albumin serves as a
      major reservoir of NO(.) and its reactive oxides and controls the dynamics of
      NO(.)-dependant processes in the vasculature.

PMID- 11983892
TI  - A chloroplast-resident DNA methyltransferase is responsible for hypermethylation
      of chloroplast genes in Chlamydomonas maternal gametes.
AB  - Chloroplast DNA of the green alga Chlamydomonas reinhardtii is maternally
      inherited. Methylation mapping directly revealed that, before mating, chloroplast
      DNA of maternal (mating type plus; mt(+)) gametes is heavily methylated whereas
      that of paternal (mating type minus; mt(-)) gametes is not. Indirect
      immunofluorescence analyses with anti-5-methylcytosine mAbs visually showed
      methylation to occur exclusively in chloroplast DNA of mt(+) gametes, and not in
      mt(-) gametes or nuclear DNA of either mt. To clarify the relationship between
      methylation and maternal inheritance of chloroplast DNA, we have isolated and
      characterized a cDNA encoding a DNA methyltransferase. The deduced protein,
      CrMET1, consists of 1,344 aa and contains a conserved catalytic domain at the C
      terminal and a nonconserved N-terminal region. The predicted N-terminal region
      has an arginine-rich domain, suggesting CrMET1 is transferred to chloroplasts.
      This finding could be directly shown by green fluorescent protein epifluorescence
      microscopy analyses. CrMET1 transcripts were found to be absent in both mt(+) and
      mt(-) vegetative cells. Upon gametogenesis, however, transcript levels clearly
      increased in mt(+) but not mt(-) cells. These experiments suggest that the CrMET1
      protein is located in chloroplasts and that it specifically methylates cytosine
      residues of chloroplast DNA in mt(+) gametes. This conclusion was further
      strengthened by the observation that, during gametogenesis, CrMET1 is expressed
      in a mt(-) mutant, mat-1, whose chloroplast DNA is heavily methylated in gametes
      and paternally inherited. The results provide evidence that cytosine methylation
      plays a critical role in maternal inheritance of chloroplast genes in C.
      reinhardtii.

PMID- 11983893
TI  - Calreticulin recognizes misfolded HLA-A2 heavy chains.
AB  - Our studies investigated functional interactions between calreticulin, an
      endoplasmic reticulum chaperone, and major histocompatibility complex (MHC) class
      I molecules. Using in vitro thermal aggregation assays, we established that
      calreticulin can inhibit heat-induced aggregation of soluble, peptide-deficient
      HLA-A2 purified from supernatants of insect cells. The presence of HLA-A2
      specific peptides also inhibits heat-induced aggregation. Inhibition of heat
      induced aggregation of peptide-deficient HLA-A2 by calreticulin correlates with a
      rescue of the HLA-A2 heavy chain from precipitation, by forming high-molecular
      weight complexes with calreticulin. Complex formation between HLA-A2 heavy chains
      and calreticulin occurs at 50 degrees C but not 37 degrees C, suggesting
      polypeptide-based interactions between the HLA-A2 heavy chain and calreticulin.
      Once complexes are formed, the addition of peptide is not sufficient to trigger
      efficient assembly of heavy chain/beta2m/peptide complexes. Using a fluorescent
      peptide-based binding assay, we show that calreticulin does not enhance peptide
      binding by HLA-A2 at 37 degrees C. We also show that calreticulin itself is
      converted to oligomeric species on exposure to 37 degrees C or higher
      temperatures, and that oligomeric forms of calreticulin are active in inhibiting
      thermal aggregation of peptide-deficient HLA-A2. Taken together, these results
      suggest that calreticulin functions in the recognition of misfolded MHC class I
      heavy chains in the endoplasmic reticulum. However, in the absence of other
      endoplasmic reticulum components, calreticulin by itself does not enhance the
      assembly of misfolded MHC class I heavy chains with beta2m and peptides.

PMID- 11983894
TI  - Direct mass spectrometric analysis of intact proteins of the yeast large
      ribosomal subunit using capillary LC/FTICR.
AB  - Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry coupled with capillary reverse-phase liquid chromatography was used
      to characterize intact proteins from the large subunit of the yeast ribosome.
      High mass measurement accuracy, achieved by "mass locking" with an internal
      standard from a dual electrospray ionization source, allowed identification of
      ribosomal proteins. Analyses of the intact proteins revealed information on
      cotranslational and posttranslational modifications of the ribosomal proteins
      that included loss of the initiating methionine, acetylation, methylation, and
      proteolytic maturation. High-resolution separations permitted differentiation of
      protein isoforms having high structural similarity as well as proteins from their
      modified forms, facilitating unequivocal assignments. The study identified 42 of
      the 43 core large ribosomal subunit proteins and 58 (of 64 possible) core large
      subunit protein isoforms having unique masses in a single analysis. These results
      demonstrate the basis for the high-throughput analyses of complex mixtures of
      intact proteins, which we believe will be an important complement to other
      approaches for defining protein modifications and their changes resulting from
      physiological processes or environmental perturbations.

PMID- 11983895
TI  - Modulation of tRNAAla identity by inorganic pyrophosphatase.
AB  - A highly sensitive assay of tRNA aminoacylation was developed that directly
      measures the fraction of aminoacylated tRNA by following amino acid attachment to
      the 3'-(32)P-labeled tRNA. When applied to Escherichia coli alanyl-tRNA
      synthetase, the assay allowed accurate measurement of aminoacylation of the most
      deleterious mutants of tRNA(Ala). The effect of tRNA(Ala) identity mutations on
      both aminoacylation efficiency (k(cat)/K(M)) and steady-state level of aminoacyl
      tRNA was evaluated in the absence and presence of inorganic pyrophosphatase and
      elongation factor Tu. Significant levels of aminoacylation were achieved for tRNA
      mutants even when the k(cat)/K(M) value is reduced by as much as several
      thousandfold. These results partially reconcile the discrepancy between in vivo
      and in vitro analysis of tRNA(Ala) identity.

PMID- 11983896
TI  - Observation by fluorescence microscopy of transcription on single combed DNA.
AB  - Molecular combing is a powerful procedure for aligning a large array of DNA
      molecules onto a surface. This technique usually leads to an overstretching of
      about 150% of the molecules' contour length. By changing the magnitude of
      capillary forces during the combing process, we were able to reduce the relative
      extension of the DNA molecules. Thus we achieved combing of T7 DNA with an
      extension close to its molecule contour length. We checked the ability of combed
      DNA to interact with DNA binding proteins. Using the T7 bacteriophage
      transcription system, we investigated the transcription activity of RNA
      polymerase on combed DNA by direct visualization of newly synthesized fluorescent
      RNAs. Our experiments show that no transcription activity occurs on overstretched
      DNA molecules, whereas we observe a transcription activity for nonoverstretched
      molecules. This activity is observed both in multiple initiation experiments and
      for one immobilized T7 RNA polymerase per promoter. These results open
      possibilities for the study of single enzyme actions on combed DNA by optical
      methods.

PMID- 11983897
TI  - Heparin-binding EGF-like growth factor mediates the biological effects of P450
      arachidonate epoxygenase metabolites in epithelial cells.
AB  - In addition to its important functions in detoxification of foreign chemicals and
      biosynthesis of steroid hormones, the cytochrome P450 enzyme system metabolizes
      arachidonate to 14,15-epoxyeicosatrienoic acid (14,15-EET). This study
      demonstrates that a P450 arachidonate epoxygenase metabolite can activate
      cleavage of heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      and delineates an essential role for HB-EGF in the mitogenic effects of this
      lipid mediator. Blockade of HB-EGF processing or EGF receptor (EGFR) inhibited
      14,15-EET-stimulated early mitogenic signals and DNA synthesis. 14,15-EET failed
      to induce mitogenesis in cell lines expressing minimal HB-EGF, whereas 14,15-EET
      induced soluble HB-EGF release into the conditioned media of cell lines that both
      express high levels of HB-EGF and display mitogenic response to this lipid
      mediator. Moreover, transfection of a bacterial 14,15-epoxygenase established
      intracellular endogenous 14,15-EET biosynthesis in cultured cell systems, which
      allowed direct confirmation of involvement of EGFR transactivation in the
      endogenous 14,15-EET-mediated mitogenic signaling pathway. This mechanism
      involves EET-dependent activation of metalloproteinases and release of the potent
      mitogenic EGFR ligand, HB-EGF.

PMID- 11983898
TI  - Estimates of lateral and longitudinal bond energies within the microtubule
      lattice.
AB  - We developed a stochastic model of microtubule (MT) assembly dynamics that
      estimates tubulin-tubulin bond energies, mechanical energy stored in the lattice
      dimers, and the size of the tubulin-GTP cap at MT tips. First, a simple
      assembly/disassembly state model was used to screen possible combinations of
      lateral bond energy (DeltaG(Lat)) and longitudinal bond energy (DeltaG(Long))
      plus the free energy of immobilizing a dimer in the MT lattice (DeltaG(S)) for
      rates of MT growth and shortening measured experimentally. This analysis predicts
      DeltaG(Lat) in the range of -3.2 to -5.7 k(B)T and DeltaG(Long) plus DeltaG(S) in
      the range of -6.8 to -9.4 k(B)T. Based on these estimates, the energy of
      conformational stress for a single tubulin-GDP dimer in the lattice is 2.1-2.5
      k(B)T. Second, we studied how tubulin-GTP cap size fluctuates with different
      hydrolysis rules and show that a mechanism of directly coupling subunit addition
      to hydrolysis fails to support MT growth, whereas a finite hydrolysis rate allows
      growth. By adding rules to mimic the mechanical constraints present at the MT
      tip, the model generates tubulin-GTP caps similar in size to experimental
      estimates. Finally, by combining assembly/disassembly and cap dynamics, we
      generate MT dynamic instability with rates and transition frequencies similar to
      those measured experimentally. Our model serves as a platform to examine GTP-cap
      dynamics and allows predictions of how MT-associated proteins and other effectors
      alter the energetics of MT assembly.

PMID- 11983899
TI  - The bimodal regulation of epidermal growth factor signaling by human Sprouty
      proteins.
AB  - Signal transduction through epidermal growth factor receptors (EGFRs) is
      essential for the growth and development of multicellular organisms. A genetic
      screen for regulators of EGFR signaling has led to the identification of Sprouty,
      a cell autonomous inhibitor of EGF signaling that is transcriptionally induced by
      the pathway. However, the molecular mechanisms by which Sprouty exerts its
      antagonistic effect remain largely unknown. Here we have used transient
      expression in human cells to investigate the functional properties of human
      Sprouty (hSpry) proteins. Ectopically expressed full-length hSpry1 and hSpry2
      induce the potentiation of EGFR-mediated mitogen-activated protein (MAP) kinase
      activation. In contrast, truncation mutants of hSpry1 and hSpry2 containing the
      highly conserved carboxyl-terminal cysteine-rich domain inhibit EGF-induced MAP
      kinase activation. The potentiating effect of the full-length hSpry2 proteins on
      EGF signaling is mediated by the amino-terminal domain and results from the
      sequestration of c-Cbl, which in turn leads to the inhibition of EGFR
      ubiquitination and degradation. These results indicate that hSpry2 can function
      both as a negative and positive regulator of EGFR-mediated MAP kinase signaling
      in a domain-dependent fashion. A dual function of this kind could provide a
      mechanism for achieving proper balance between the activation and repression of
      EGFR signaling.

PMID- 11983901
TI  - A single domestication for maize shown by multilocus microsatellite genotyping.
AB  - There exists extraordinary morphological and genetic diversity among the maize
      landraces that have been developed by pre-Columbian cultivators. To explain this
      high level of diversity in maize, several authors have proposed that maize
      landraces were the products of multiple independent domestications from their
      wild relative (teosinte). We present phylogenetic analyses based on 264
      individual plants, each genotyped at 99 microsatellites, that challenge the
      multiple-origins hypothesis. Instead, our results indicate that all maize arose
      from a single domestication in southern Mexico about 9,000 years ago. Our
      analyses also indicate that the oldest surviving maize types are those of the
      Mexican highlands with maize spreading from this region over the Americas along
      two major paths. Our phylogenetic work is consistent with a model based on the
      archaeological record suggesting that maize diversified in the highlands of
      Mexico before spreading to the lowlands. We also found only modest evidence for
      postdomestication gene flow from teosinte into maize.

PMID- 11983900
TI  - The LEF1/beta -catenin complex activates movo1, a mouse homolog of Drosophila ovo
      required for epidermal appendage differentiation.
AB  - Drosophila ovo/svb (dovo) is required for epidermal cuticle/denticle
      differentiation and is genetically downstream of the wg signaling pathway.
      Similarly, a mouse homolog of dovo, movo1, is required for the proper formation
      of hair, a mammalian epidermal appendage. Here, we provide biochemical evidence
      that movo1 encodes a nuclear DNA binding protein (mOvo1a) that binds to DNA
      sequences similar to those that dOvo binds to, further supporting the notion that
      mOvo1a and dOvo are genetically and biochemically homologous proteins.
      Additionally, we show that the movo1 promoter is activated by the lymphoid
      enhancer factor 1 (LEF1)/beta-catenin complex, a transducer of wnt signaling.
      Collectively, our findings suggest that movo1 is a developmental target of wnt
      signaling during hair morphogenesis in mice, and that the wg/wnt-ovo link in
      epidermal appendage regulatory pathways has been conserved between mice and
      flies.

PMID- 11983902
TI  - The global phylogeny of glycolytic enzymes.
AB  - Genes encoding the glycolytic enzymes of the facultative endocellular parasite
      Bartonella henselae have been analyzed phylogenetically within a very large
      cohort of homologues from bacteria and eukaryotes. We focus on this relative of
      Rickettsia prowazekii along with homologues from other alpha-proteobacteria to
      determine whether there have been systematic transfers of glycolytic genes from
      the presumed alpha-proteobacterial ancestor of the mitochondrion to the nucleus
      of the early eukaryote. The alpha-proteobacterial homologues representing the
      eight glycolytic enzymes studied here tend to cluster in well-supported nodes.
      Nevertheless, not one of these alpha-proteobacterial enzymes is related as a
      sister clade to the corresponding eukaryotic homologues. Nor is there a close
      phylogenetic relationship between glycolytic genes from Eucarya and any other
      bacterial phylum. In contrast, several of the reconstructions suggest that there
      may have been systematic transfer of sequences encoding glycolytic enzymes from
      cyanobacteria to some green plants. Otherwise, surprisingly little exchange
      between the bacterial and eukaryotic domains is observed. The descent of
      eukaryotic genes encoding enzymes of intermediary metabolism is reevaluated.

PMID- 11983903
TI  - Mutator clones of Neisseria meningitidis in epidemic serogroup A disease.
AB  - Serogroup A Neisseria meningitidis has repeatedly caused widespread epidemics of
      meningitis and septicemia throughout the 20th century. Recently, in a limited
      collection of strains, epidemic serogroup A isolates were found to have elevated
      mutation rates that was caused by defects in mismatch repair pathways. To
      ascertain the role of these mutators in the epidemic spread of this serogroup,
      the prevalence of hypermutability in a collection of 95 serogroup A N.
      meningitidis invasive isolates was determined. Overall mutability in Neisseriae
      can be described by measuring both missense mutation rates as well as phase
      variation frequencies of "contingency loci." Fifty-seven percent of serogroup A
      isolates possessed elevated mutability, which could be divided into two classes:
      intermediate and high level. Eleven of 20 high-level mutators, with phase
      variation rates >100-fold higher than wild-type isolates, were defective in
      mismatch repair. Ten of the 34 intermediate mutators possessing >10-fold
      increases in phase variation rates could be partially complemented by a wild-type
      mutL allele. A high prevalence of mutators in epidemic isolates indicates that
      hypermutability may play a major role in the transmission of this pathogen. The
      added diversity derived from increased phase variation rates may allow fixation
      of mutator alleles more frequently during epidemic spread.

PMID- 11983904
TI  - Intron evolution as a population-genetic process.
AB  - Debate over the mechanisms responsible for the phylogenetic and genomic
      distribution of introns has proceeded largely without consideration of the
      population-genetic forces influencing the establishment and retention of novel
      genetic elements. However, a simple model incorporating random genetic drift and
      weak mutation pressure against intron-containing alleles yields predictions
      consistent with a diversity of observations: (i) the rarity of introns in
      unicellular organisms with large population sizes, and their expansion after the
      origin of multicellular organisms with reduced population sizes; (ii) the
      relationship between intron abundance and the stringency of splice-site
      requirements; (iii) the tendency for introns to be more numerous and longer in
      regions of low recombination; and (iv) the bias toward phase-0 introns. This
      study provides a second example of a mechanism whereby genomic complexity
      originates passively as a "pathological" response to small population size, and
      raises difficulties for the idea that ancient introns played a major role in the
      origin of genes by exon shuffling.

PMID- 11983905
TI  - Dental microstructure and life history in subfossil Malagasy lemurs.
AB  - When compared with their recently extinct relatives, living lemurs represent a
      mere fraction of a broad radiation that occupied unique niches in the recent
      past. Among living lemurs, indrids exhibit the fastest rates of dental
      development. This dental precocity is tightly correlated with rapid pace of
      postnatal dental eruption, early replacement of the deciduous teeth, high dental
      endowment at weaning, and relatively slow somatic growth. This pattern is in
      stark contrast to that seen in extant lemurids, where somatic development is
      highly accelerated and dental development is relatively slow. We report on the
      pace of dental development in one species of palaeopropithecid, the sister group
      to extant indrids. Like much smaller modern indrids, the chimpanzee-sized
      Palaeopropithecus ingens was dentally precocious at birth as evidenced by the
      advanced state of molar crown formation. This finding implies a pattern
      characteristic of Propithecus and other indrids-rapid dental development despite
      relatively prolonged gestation. Gestation length in this one species of subfossil
      lemur was likely greater than 9 months. Our results demonstrate that large body
      size in primates does not preclude exceedingly rapid dental development.

PMID- 11983906
TI  - Evolutionary conservation of zebrafish linkage group 14 with frequently deleted
      regions of human chromosome 5 in myeloid malignancies.
AB  - Recurring interstitial loss of all or part of the long arm of chromosome 5,
      del(5q), is a hallmark of myelodysplastic syndrome and acute myeloid leukemia.
      Although the genes affected by these changes have not been identified, two
      critically deleted regions (CDRs) are well established. We have identified 76
      zebrafish cDNAs orthologous to genes located in these 5q CDRs. Radiation hybrid
      mapping revealed that 33 of the 76 zebrafish orthologs are clustered in a genomic
      region on linkage group 14 (LG14). Fifteen others are located on LG21, and two on
      LG10. Although there are large blocks of conserved syntenies, the gene order
      between human and zebrafish is extensively inverted and transposed. Thus,
      intrachromosomal rearrangements and inversions appear to have occurred more
      frequently than translocations during evolution from a common chordate ancestor.
      Interestingly, of the 33 orthologs located on LG14, three have duplicates on
      LG21, suggesting that the duplication event occurred early in the evolution of
      teleosts. Murine orthologs of human 5q CDR genes are distributed among three
      chromosomes, 18, 11, and 13. The order of genes within the three syntenic mouse
      chromosomes appears to be more colinear with the human order, suggesting that
      translocations occurred more frequently than inversions during mammalian
      evolution. Our comparative map should enhance understanding of the evolution of
      the del(5q) chromosomal region. Mutant fish harboring deletions affecting the 5q
      CDR syntenic region may provide useful animal models for investigating the
      pathogenesis of myelodysplastic syndrome and acute myeloid leukemia.

PMID- 11983907
TI  - Reverse engineering gene networks using singular value decomposition and robust
      regression.
AB  - We propose a scheme to reverse-engineer gene networks on a genome-wide scale
      using a relatively small amount of gene expression data from microarray
      experiments. Our method is based on the empirical observation that such networks
      are typically large and sparse. It uses singular value decomposition to construct
      a family of candidate solutions and then uses robust regression to identify the
      solution with the smallest number of connections as the most likely solution. Our
      algorithm has O(log N) sampling complexity and O(N(4)) computational complexity.
      We test and validate our approach in a series of in numero experiments on model
      gene networks.

PMID- 11983908
TI  - Asymmetrical flagellar rotation in Borrelia burgdorferi nonchemotactic mutants.
AB  - The Lyme disease spirochete Borrelia burgdorferi has bundles of periplasmic
      flagella subpolarly located at each cell end. These bundles rotate in opposite
      directions during translational motility. When not translating, they rotate in
      the same direction, and the cells flex. Here, we present evidence that
      asymmetrical rotation of the bundles during translation does not depend upon the
      chemotaxis signal transduction system. The histidine kinase CheA is known to be
      an essential component in the signaling pathway for bacterial chemotaxis. Mutants
      of cheA in flagellated bacteria continually rotate their flagella in one
      direction. B. burgdorferi has two copies of cheA designated cheA1 and cheA2. Both
      genes were found to be expressed in growing cells. We reasoned that if chemotaxis
      were essential for asymmetrical rotation of the flagellar bundles, and if the
      flagellar motors at both cell ends were identical, inactivation of the two cheA
      genes should result in cells that constantly flex. To test this hypothesis, the
      signaling pathway was completely blocked by constructing the double mutant
      cheA1kan cheA2ermC. This double mutant was deficient in chemotaxis. Rather than
      flexing, it failed to reverse, and it continually translated only in one
      direction. Video microscopy of mutant cells indicated that both bundles actively
      rotated. The results indicate that asymmetrical rotation of the flagellar bundles
      of spirochetes does not depend upon the chemotaxis system but rather upon
      differences between the two flagellar bundles. We propose that certain factors
      within the spirochete localize at the flagellar motors at one end of the cell to
      effect this asymmetry.

PMID- 11983909
TI  - Recall and propagation of allospecific memory T cells independent of secondary
      lymphoid organs.
AB  - The allospecifc T cell population responding to a transplanted organ consists of
      both naive and memory lymphocytes. Although it is established that naive T cells
      are activated by antigen within the organized structures of secondary lymphoid
      organs (the spleen, lymph nodes, and mucosal lymphoid tissues), it is not clear
      whether memory T cell activation and propagation depend on homing to these
      organs. To answer this question, we investigated whether allospecific naive or
      memory T cells can mediate acute cardiac allograft rejection in mutant mice that
      lack all of their secondary lymphoid tissues. The results of our experiments
      demonstrated that antigen-experienced memory T cells have two advantages over
      naive T cells: (i) memory T cells mount a vigorous immune response that leads to
      allograft rejection independent of secondary lymphoid organs; and (ii) memory T
      cells generate more memory T cells without homing to secondary lymphoid organs.
      These unique properties of memory T cells were further confirmed by showing that
      memory-like T cells that arise from the homeostatic proliferation of naive T
      cells in the absence of antigenic stimulation are suboptimal at rejecting
      allografts and do not generate memory T cells in mice devoid of secondary
      lymphoid tissues.

PMID- 11983910
TI  - ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2
      cytokine secretion by memory CD4+ T cells.
AB  - Endothelial cells (EC) play a central role in inflammatory immune responses and
      efficiently induce effector functions in T cells, despite lacking the classical
      costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate
      that human inducible costimulator-ligand (ICOS-L), a molecule related to
      CD80/CD86, is constitutively expressed on human EC in vivo. In vitro, ICOS-L
      expression was strongly enhanced on human umbilical vein EC and microvascular EC
      by the inflammatory cytokines tumor necrosis factor alpha and IL-1beta, and to a
      lower extent by stimulation of EC by CD40 or lipopolysaccharide. Coculture of MHC
      class II(+) EC with resting memory CD4(+) T cells in the presence of superantigen
      led to a marked up-regulation of ICOS on T cells and to the production of Th1
      (IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-10, IL-13). When these cocultures
      were performed in the presence of the inhibitory mAb HIL-131, secretion of all
      cytokines was reduced by about 50-80%, indicating that ICOS-L is a major
      costimulator in EC-mediated T cell activation. Taken together, our data suggest
      an important physiological role of ICOS-L in the reactivation of effector/memory
      T cells on the endothelium controlling the entry of immune cells into inflamed
      tissue.

PMID- 11983911
TI  - Generation of functional antigen-specific T cells in defined genetic backgrounds
      by retrovirus-mediated expression of TCR cDNAs in hematopoietic precursor cells.
AB  - We have developed an alternative to transgenesis for producing antigen-specific T
      cells in vivo. In this system, clonal naive T cells with defined antigen
      specificity are generated by retrovirus-mediated expression of T cell antigen
      receptor cDNAs in RAG1-deficient murine hematopoietic precursor cells. These T
      cells can be stimulated to proliferate and produce cytokines by exposure to
      antigen in vitro, and they become activated and expand in vivo after
      immunization. IL-2-deficient T cells generated by this technique show decreased
      proliferation and cytokine production, both of which can be rescued by exogenous
      addition of this growth factor. Thus, retrovirus-mediated expression of T cell
      antigen receptor cDNAs in hematopoietic precursor cells permits the rapid and
      efficient analysis of the life history of antigen-specific T cells in different
      genetic backgrounds and may allow for the long-term production of antigen
      specific T cells with different functional properties for prophylactic and
      therapeutic purposes.

PMID- 11983912
TI  - Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a
      role of retinoschisin in retinal cell layer organization and synaptic structure.
AB  - Deleterious mutations in RS1 encoding retinoschisin are associated with X-linked
      juvenile retinoschisis (RS), a common form of macular degeneration in males. The
      disorder is characterized by a negative electroretinogram pattern and by a
      splitting of the inner retina. To gain further insight into the function of the
      retinoschisin protein and its role in the cellular pathology of RS, we have
      generated knockout mice deficient in Rs1h, the murine ortholog of the human RS1
      gene. We show that pathologic changes in hemizygous Rs1h(-/Y) male mice are
      evenly distributed across the retina, apparently contrasting with the macula
      dominated features in human. Similar functional anomalies in human and Rs1h(-/Y)
      mice, however, suggest that both conditions are a disease of the entire retina
      affecting the organization of the retinal cell layers as well as structural
      properties of the retinal synapse.

PMID- 11983913
TI  - Neutrophils are indispensable for hematopoietic stem cell mobilization induced by
      interleukin-8 in mice.
AB  - The CXC chemokine interleukin-8 (IL-8/CXCL8) induces rapid mobilization of
      hematopoietic progenitor cells (HPCs). Previously we showed that mobilization
      could be prevented completely in mice by pretreatment with neutralizing
      antibodies against the beta2-integrin LFA-1 (CD11a). In addition, murine HPCs do
      not express LFA-1, indicating that mobilization requires a population of
      accessory cells. Here we show that polymorphonuclear cells (PMNs) serve as key
      regulators in IL-8-induced HPC mobilization. The role of PMNs was studied in mice
      rendered neutropenic by administration of a single injection of antineutrophil
      antibodies. Absolute neutropenia was observed up to 3-5 days with a rebound
      neutrophilia at day 7. The IL-8-induced mobilizing capacity was reduced
      significantly during the neutropenic phase, reappeared with recurrence of the
      PMNs, and was increased proportionally during the neutrophilic phase. In
      neutropenic mice, the IL-8-induced mobilizing capacity was restored by the
      infusion of purified PMNs but not by infusion of mononuclear cells. Circulating
      metalloproteinase gelatinase B (MMP-9) levels were detectable only in neutropenic
      animals treated with PMNs in combination with IL-8, showing that in vivo
      activated PMNs are required for the restoration of mobilization. However, IL-8
      induced mobilization was not affected in MMP-9-deficient mice, indicating that
      MMP-9 is not indispensable for mobilization. These data demonstrate that IL-8
      induced mobilization of HPCs requires the in vivo activation of circulating PMNs.

PMID- 11983914
TI  - Differential regulation of the human and murine CD34 genes in hematopoietic stem
      cells.
AB  - Human CD34 (hCD34)-positive cells are used currently as a source for
      hematopoietic transplantation in humans. However, in steady-state murine
      hematopoiesis, hematopoietic stem cells (HSCs) with long-term reconstitution
      activity are found almost exclusively in the murine CD34 (mCD34)-negative to low
      fraction. To evaluate the possible differences in hCD34 and mCD34 gene expression
      in hematopoiesis, we made transgenic mouse strains with human genomic P1
      artificial chromosome clones spanning the entire hCD34 genomic locus. In all
      transgenic mouse strains, a vast majority of phenotypic and functional HSC
      populations including mCD34(-/lo) express the hCD34 transgene. These data
      strongly support the notion that hCD34(+) human bone marrow cells contain long
      term HSCs that can maintain hematopoiesis throughout life.

PMID- 11983915
TI  - bcl-2 overexpression promotes myocyte proliferation.
AB  - To determine the influence of Bcl-2 on the developmental biology of myocytes, we
      analyzed the population dynamics of this cell type in the heart of transgenic
      (TG) mice overexpressing Bcl-2 under the control of the alpha-myosin heavy chain
      promoter. TG mice and non-TG (wild type, WT) mice were studied at 24 days, 2
      months, and 4 months after birth. Bcl-2 overexpression produced a significant
      increase in the percentage of cycling myocytes and their mitotic index. These
      effects were strictly connected to the expression of the transgene, as
      demonstrated in isolated myocytes. The formation of mitotic spindle and
      contractile ring was identified in replicating cells. These typical aspects of
      mitosis were complemented with the demonstration of karyokinesis and cytokinesis
      to provide structural evidence of cell division. Apoptosis was low at all ages
      and was not affected by Bcl-2. The higher cell replication rate in TG was
      conditioned by a decrease in the expression of the cell-cycle inhibitors,
      p21(WAF1) and p16(INK4a), and by an increase in Mdm2-p53 complexes. In comparison
      with WT, TG had 0.4 x 10(6), 0.74 x 10(6), and 1.2 x 10(6) more myocytes in the
      left ventricle at 24 days, 2 months, and 4 months, respectively. Binucleated
      myocytes were 12% and 25% larger in WT than in TG mice at 2 and 4 months of age.
      Taken together, these observations reveal a previously uncharacterized
      replication-enhancing function of Bcl-2 in myocytes in vivo in the absence of
      stressful conditions.

PMID- 11983916
TI  - Characterization of the c-MYC-regulated transcriptome by SAGE: identification and
      analysis of c-MYC target genes.
AB  - To identify target genes of the oncogenic transcription factor c-MYC, serial
      analysis of gene expression (SAGE) was performed after adenoviral expression of c
      MYC in primary human umbilical vein endothelial cells: 216 different SAGE tags,
      corresponding to unique mRNAs, were induced, whereas 260 tags were repressed
      after c-MYC expression (P < 0.05). The induction of 53 genes was confirmed by
      using microarray analysis and quantitative real-time PCR: among these genes was
      MetAP2/p67, which encodes an activator of translational initiation and represents
      a validated target for inhibition of neovascularization. Furthermore, c-MYC
      induced the cell cycle regulatory genes CDC2-L1, Cyclin E binding protein 1, and
      Cyclin B1. The DNA repair genes BRCA1, MSH2, and APEX were induced by c-MYC,
      suggesting that c-MYC couples DNA replication to processes preserving the
      integrity of the genome. MNT, a MAX-binding antagonist of c-MYC function, was up
      regulated, implying a negative feedback loop. In vivo promoter occupancy by c-MYC
      was detected by chromatin immunoprecipitation for CDK4, Prohibitin, MNT, Cyclin
      B1, and Cyclin E binding protein 1, showing that these genes are direct c-MYC
      targets. The c-MYC-regulated genes/tags identified here will help to define the
      set of bona fide c-MYC targets and may have potential therapeutic value for
      inhibition of cancer cell proliferation, tumor-vascularization, and restenosis.

PMID- 11983917
TI  - Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol
      level and foam cell lesion size.
AB  - Inflammatory cytokines have been linked to atherosclerosis by using cell culture
      models and acute inflammation in animals. The goal of this study was to examine
      lipoprotein levels and early atherosclerosis in chronic animal models of altered
      IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist
      (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo
      had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend
      toward increased foam-cell lesion area compared to wild-type littermate controls.
      IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a
      cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high
      density lipoprotein cholesterol, consistent with the IL-1ra knockout data,
      although there was no change in lesion size. When these IL1-ra overexpressing
      transgenic mice on the LDLR knockout background were fed a high-cholesterol/high
      fat diet containing cholate, however, a statistically significant 40% decrease in
      lesion area was observed compared to LDLR knockout mice lacking the transgene. By
      immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae,
      absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL
      1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein
      levels and, when fed a cholate-containing diet, decrease foam-cell lesion size.
      These data demonstrate that in selected models of murine atherosclerosis, chronic
      IL-1ra depletion or overexpression has potentially important effects on
      lipoprotein metabolism and foam-cell lesion development.

PMID- 11983918
TI  - Gene expression analysis reveals matrilysin as a key regulator of pulmonary
      fibrosis in mice and humans.
AB  - Pulmonary fibrosis is a progressive and largely untreatable group of disorders
      that affects up to 100,000 people on any given day in the United States. To
      elucidate the molecular mechanisms that lead to end-stage human pulmonary
      fibrosis we analyzed samples from patients with histologically proven pulmonary
      fibrosis (usual interstitial pneumonia) by using oligonucleotide microarrays.
      Gene expression patterns clearly distinguished normal from fibrotic lungs. Many
      of the genes that were significantly increased in fibrotic lungs encoded proteins
      associated with extracellular matrix formation and degradation and proteins
      expressed in smooth muscle. Using a combined set of scoring systems we determined
      that matrilysin (matrix metalloproteinase 7), a metalloprotease not previously
      associated with pulmonary fibrosis, was the most informative increased gene in
      our data set. Immunohistochemisry demonstrated increased expression of matrilysin
      protein in fibrotic lungs. Furthermore, matrilysin knockout mice were
      dramatically protected from pulmonary fibrosis in response to intratracheal
      bleomycin. Our results identify matrilysin as a mediator of pulmonary fibrosis
      and a potential therapeutic target. They also illustrate the power of global gene
      expression analysis of human tissue samples to identify molecular pathways
      involved in clinical disease.

PMID- 11983919
TI  - Heparan sulfate proteoglycan-dependent induction of axon branching and axon
      misrouting by the Kallmann syndrome gene kal-1.
AB  - Kallmann syndrome is a neurological disorder characterized by various behavioral
      and neuroanatomical defects. The X-linked form of this disease is caused by
      mutations in the KAL-1 gene, which codes for a secreted molecule that is
      expressed in restricted regions of the brain. Its molecular mechanism of action
      has thus far remained largely elusive. We show here that expression of the
      Caenorhabditis elegans homolog of KAL-1 in selected sensory and interneuron
      classes causes a highly penetrant, dosage-dependent, and cell autonomous axon
      branching phenotype. In a different cellular context, heterologous C. elegans kal
      1 expression causes a highly penetrant axon-misrouting phenotype. The axon
      branching and -misrouting activities require different domains of the KAL-1
      protein. In a genetic modifier screen we isolated several loci that either
      suppress or enhance the kal-1-induced axonal defects, one of which codes for an
      enzyme that modifies specific residues in heparan sulfate proteoglycans, namely
      heparan-6O-sulfotransferase. We hypothesize that KAL-1 binds by means of a
      heparan sulfate proteoglycan to its cognate receptor or other extracellular cues
      to induce axonal branching and axon misrouting.

PMID- 11983920
TI  - Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation
      inducing electrical stimulation patterns.
AB  - The neurotrophin (NT) brain-derived neurotrophic factor (BDNF) plays an essential
      role in the formation of long-term potentiation (LTP). Here, we address whether
      this modulation by BDNF requires its continuous presence, or whether a local
      increase in BDNF is necessary during a specific time period of LTP initiation.
      Using electrical field stimulation of primary cultures of hippocampal neurons, we
      demonstrate that short high-frequency bursts of stimuli that induce LTP evoke
      also an instantaneous secretion of BDNF. In contrast, stimuli at low frequencies,
      inducing long-term depression, do not enhance BDNF secretion, suggesting that
      BDNF is specifically present, and thus required, at the time of LTP induction.
      The field-stimulation-mediated BDNF secretion depends on the formation of action
      potentials and is induced by IP(3)-mediated Ca(2+) release from intracellular
      stores. Experiments, aimed at determining the sites of NT secretion that use NT6,
      showed similar patterns of surface labeling by field stimulation to those shown
      previously by high potassium.

PMID- 11983921
TI  - Visualization of Ca2+ entry through single stretch-activated cation channels.
AB  - Stretch-activated channels (SACs) have been found in smooth muscle and are
      thought to be involved in myogenic responses. Although SACs have been shown to be
      Ca(2+) permeable when Ca(2+) is the only charge carrier, it has not been clearly
      demonstrated that significant Ca(2+) passes through SACs in physiological
      solutions. By imaging at high temporal and spatial resolution the single-channel
      Ca(2+) fluorescence transient (SCCaFT) arising from Ca(2+) entry through a single
      SAC opening, we provide direct evidence that significant Ca(2+) can indeed pass
      through SACs and increase the local [Ca(2+)]. Results were obtained under
      conditions where the only source of Ca(2+) was the physiological salt solution in
      the patch pipette containing 2 mM Ca(2+). Single smooth muscle cells were loaded
      with fluo-3 acetoxymethyl ester, and the fluorescence was recorded by using a
      wide-field digital imaging microscope while SAC currents were simultaneously
      recorded from cell-attached patches. Fluorescence increases at the cell-attached
      patch were clearly visualized before the simultaneous global Ca(2+) increase that
      occurred because of Ca(2+) influx through voltage-gated Ca(2+) channels when the
      membrane was depolarized by inward SAC current. From measurements of total
      fluorescence ("signal mass") we determined that about 18% of the SAC current is
      carried by Ca(2+) at membrane potentials more negative than the resting level.
      This would translate into at least a 0.35-pA unitary Ca(2+) current at the
      resting potential. Such Ca(2+) currents passing through SACs are sufficient to
      activate large-conductance Ca(2+)-activated K(+) channels and, as shown
      previously, to trigger Ca(2+) release from intracellular stores.

PMID- 11983922
TI  - Ectopic D-type cyclin expression induces not only DNA replication but also cell
      division in Arabidopsis trichomes.
AB  - Although the mechanisms controlling the two cell-cycle checkpoints G(1)-S and
      G(2)-M are well studied, it remains elusive how they are linked in higher
      eukaryotes. In animals, D-type cyclins have been implicated in the control of
      cell-cycle progression in mitotic as well as in endoreduplicating cells. By
      contrast, we show that the expression of the D-type cyclin CYCD3;1 in
      endoreduplicating Arabidopsis trichome cells not only induced DNA replication but
      also cell divisions.

PMID- 11983923
TI  - Expression and disruption of the Arabidopsis TOR (target of rapamycin) gene.
AB  - TOR (target of rapamycin) protein kinases were identified in yeasts, mammals, and
      Drosophila as central controllers of cell growth in response to nutrient and
      growth factors. Here we show that Arabidopsis thaliana possesses a single TOR
      gene encoding a protein able to complex with yeast 12-kDa FK506-binding protein
      and rapamycin despite the insensitivity of Arabidopsis vegetative growth to
      rapamycin. Analysis of two T-DNA insertion mutants shows that disruption of AtTOR
      leads to the premature arrest of endosperm and embryo development. A T-DNA
      mediated translational fusion of AtTOR with the GUS reporter gene allows us to
      show that AtTOR is expressed in primary meristem, embryo, and endosperm, but not
      in differentiated cells. The implications of these features for the plant TOR
      pathway are discussed.

PMID- 11983924
TI  - Combining constitutive materials modeling with atomic force microscopy to
      understand the mechanical properties of living cells.
AB  - The goal of this work is to study the properties of living cells and cell
      membranes by using atomic force microscopy. During atomic force microscopy (AFM)
      measurement, there is a strong mechanical coupling between the AFM tip and the
      cell. The purpose of this paper is to present a model of the overall mechanical
      response of the cell that allows us to separate out the mechanical response of
      the cell from the local surface interactions we wish to quantify. These local
      interactions include recognition (or binding) events between molecules bound to
      an AFM tip (e.g., an antibody) and molecules or receptors on the cell surface
      (e.g., the respective antigen). The computational model differs from traditional
      Hertzian contact models by explicitly taking into account the mechanics of the
      biomembrane and cytoskeleton. The model also accounts for the mechanical response
      of the living cell during arbitrary deformation. The indentation of a bovine
      sperm cell is used to test the validity of this model, and further experiments
      are proposed to fully parameterize the model.

PMID- 11983925
TI  - Distributed response analysis of conductive behavior in single molecules.
AB  - The ab initio computational approach of distributed response analysis is used to
      quantify how electrons move across conjugated molecules in an electric field, in
      analogy to conduction. The method promises to be valuable for characterizing the
      conductive behavior of single molecules in electronic devices.

PMID- 11983926
TI  - SOFTDOCK: understanding of molecular recognition through a systematic docking
      study.
AB  - Molecular recognition and docking are essential to the biological functions of
      proteins. SOFTDOCK was one of the first molecular docking methods developed for
      protein-protein docking. Its ability to represent the molecular surface with
      different shapes and properties and to dock a variety of molecular complexes with
      certain conformational changes was demonstrated in a previous study. In the
      present work, we studied the effects of the docking parameters through
      statistical analysis. Seventy one typical binary complexes of different
      categories in PDB were also systematically docked for a test; 57 of them produced
      correct solutions with one set of docking parameters whereas the other 14
      complexes required adjustment of the docking parameters, by decreasing the
      softness of the recognition and hence the background noise. We found that these
      14 complexes had special structural features. Our results suggest that a variety
      of mechanisms may be involved in molecular recognition rather than the shape
      complementarity only, which is very helpful in developing more powerful methods
      for predicting molecular recognition.

PMID- 11983927
TI  - Analysis of homodimeric protein interfaces by graph-spectral methods.
AB  - The quaternary structures impart structural and functional credibility to
      proteins. In a multi-subunit protein, it is important to understand the factors
      that drive the association or dissociation of the subunits. It is a well known
      fact that both hydrophobic and charged interactions contribute to the stability
      of the protein interface. The interface residues are also known to be highly
      conserved. Though they are buried in the oligomer, these residues are either
      exposed or partially exposed in the monomer. It is felt that a systematic and
      objective method of identifying interface clusters and their analysis can
      significantly contribute to the identification of a residue or a collection of
      residues important for oligomerization. Recently, we have applied the techniques
      of graph-spectral methods to a variety of problems related to protein structure
      and folding. A major advantage of this methodology is that the problem is viewed
      from a global protein topology point of view rather than localized regions of the
      protein structure. In the present investigation, we have applied the methods of
      graph-spectral analysis to identify side chain clusters at the interface and the
      centers of these clusters in a set of homodimeric proteins. These clusters are
      analyzed in terms of properties such as amino acid composition, accessibility to
      solvent and conservation of residues. Interesting results such as participation
      of charged and aromatic residues like arginine, glutamic acid, histidine,
      phenylalanine and tyrosine, consistent with earlier investigations, have emerged
      from these analyses. Important additional information is that the residues
      involved are a part of a cluster(s) and that they are sequentially distant
      residues which have come closer to each other in the three-dimensional structure
      of the protein. These residues can easily be detected using our graph-spectral
      algorithm. This method has also been used to identify important residues ('hot
      spots') in dimerization and also to detect dimerization sites on the monomer. The
      residues predicted using the present algorithm have correlated well with the
      experiments indicating the efficacy of this method in predicting residues
      involved in dimer stability.

PMID- 11983928
TI  - A divide and conquer approach to fast loop modeling.
AB  - We describe a fast ab initio method for modeling local segments in protein
      structures. The algorithm is based on a divide and conquer approach and uses a
      database of precalculated look-up tables, which represent a large set of possible
      conformations for loop segments of variable length. The target loop is
      recursively decomposed until the resulting conformations are small enough to be
      compiled analytically. The algorithm, which is not restricted to any specific
      loop length, generates a ranked set of loop conformations in 20-180 s on a
      desktop PC. The prediction quality is evaluated in terms of global RMSD.
      Depending on loop length the top prediction varies between 1.06 A RMSD for three
      residue loops and 3.72 A RMSD for eight-residue loops. Due to its speed the
      method may also be useful to generate alternative starting conformations for
      complex simulations.

PMID- 11983929
TI  - Prediction of proteasome cleavage motifs by neural networks.
AB  - We present a predictive method that can simulate an essential step in the antigen
      presentation in higher vertebrates, namely the step involving the proteasomal
      degradation of polypeptides into fragments which have the potential to bind to
      MHC Class I molecules. Proteasomal cleavage prediction algorithms published so
      far were trained on data from in vitro digestion experiments with constitutive
      proteasomes. As a result, they did not take into account the characteristics of
      the structurally modified proteasomes--often called immunoproteasomes--found in
      cells stimulated by gamma-interferon under physiological conditions. Our
      algorithm has been trained not only on in vitro data, but also on MHC Class I
      ligand data, which reflect a combination of immunoproteasome and constitutive
      proteasome specificity. This feature, together with the use of neural networks, a
      non-linear classification technique, make the prediction of MHC Class I ligand
      boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage
      sites are correctly determined. Moreover, we show that the neural networks
      trained on the constitutive proteasome data learns a specificity that differs
      from that of the networks trained on MHC Class I ligands, i.e. the specificity of
      the immunoproteasome is different than the constitutive proteasome. The tools
      developed in this study in combination with a predictor of MHC and TAP binding
      capacity should give a more complete prediction of the generation and
      presentation of peptides on MHC Class I molecules. Here we demonstrate that such
      an approach produces an accurate prediction of the CTL the epitopes in HIV Nef.
      The method is available at www.cbs.dtu.dk/services/NetChop/.

PMID- 11983930
TI  - Model of Vibrio cholerae toxin coregulated pilin capable of filament formation.
AB  - A complete three-dimensional model (RCSB001169; PDB code 1qqz ) for the Vibrio
      cholerae toxin coregulated pilus protein (TcpA), including residues 1-197, is
      presented. We have used the crystal structure of the Neisseria gonorrhoeae pilin
      (PilE), available biochemical data about TcpA, variations in the primary
      sequences of TcpA among various Vibrio cholerae strains and secondary structure
      prediction, hydrophilicity, surface probability and antigenicity plots for TcpA
      to build our model. In our TcpA model, the first 137 residues possess a structure
      similar to the PilE, but the remainder is different. Though the ladle shape is
      still preserved, TcpA possesses a larger ladle head or globular domain compared
      to PilE. Using this model, it has been possible to identify two kinds of
      conserved residues: (i) those forming the core of the TcpA monomer and (ii) those
      involved in the monomer-monomer interactions leading to fibre formation. Residues
      on the fibre exterior, important in the mediation of bacterium (pilus)-bacterium
      (pilus) and bacterium (pilus)-host interactions, show more variability in
      comparison to those of (i) and (ii).

PMID- 11983931
TI  - Proteo-chemometrics analysis of MSH peptide binding to melanocortin receptors.
AB  - The published data for six melanocortin peptides binding to wild-type and
      chimeric melanocortin MC(1)/MC(3) receptors were analysed using the novel proteo
      chemometrics modelling approach. The chimeric receptors and the peptides were
      coded using binary descriptors and used to correlate with the experimental data
      for affinity or selectivity for peptides binding to receptors. Correlations were
      achieved using partial least squares projection to latent structures (PLS) and
      statistically valid models were obtained. The models were further improved by
      adding cross-terms and applying orthogonal signal correction. The models were
      validated using external prediction, with half of the data being excluded from
      the modelling. Interpretation of the results using PLS coefficient plots revealed
      that the binding pocket for the melanocortins is located between the first,
      second, third, sixth and seventh transmembrane regions of the melanocortin
      receptors, in good agreement with previous three-dimensional models for the
      interactions of melanocortins with melanocortin receptors. Further, analysis of
      cross-terms between peptide descriptors indicated that the proteo-chemometrics
      modelling is able to distinguish between differences in the conformational space
      of the peptides that affect binding affinity and selectivity.

PMID- 11983932
TI  - Molecular modelling and site-directed mutagenesis of human GALR1 galanin receptor
      defines determinants of receptor subtype specificity.
AB  - Human galanin is a 30 amino acid neuropeptide that elicits a range of biological
      activities by interaction with G protein-coupled receptors. We have generated a
      model of the human GALR1 galanin receptor subtype (hGALR1) based on the alpha
      carbon maps of frog rhodopsin and investigated the significance of potential
      contact residues suggested by the model using site-directed mutagenesis. Mutation
      of Phe186 within the second extracellular loop to Ala resulted in a 6-fold
      decrease in affinity for galanin, representing a change in free energy consistent
      with hydrophobic interaction. Our model suggests interaction between Phe186 of
      hGALR1 and Ala7 or Leu11 of galanin. Receptor subtype specificity was
      investigated by replacement of residues in hGALR1 with the corresponding residues
      in hGALR2 and use of the hGALR2-specific ligands hGalanin(2-30) and [D
      Trp2]hGalanin(1-30). The His267Ile mutant receptor exhibited a pharmacological
      profile corresponding to that of hGALR1, suggesting that His267 is not involved
      in a receptor-ligand interaction. The mutation Phe115Ala resulted in a decreased
      binding affinity for hGalanin and for hGALR2-specific analogues, indicating
      Phe115 to be of structural importance to the ligand binding pocket of hGALR1 but
      not involved in direct ligand interaction. Analysis of Glu271Trp suggested that
      Glu271 of hGALR1 interacts with the N-terminus of galanin and that the Trp
      residue in the corresponding position in hGALR2 is involved in receptor subtype
      specificity of binding. Our model supports previous reports of Phe282 of hGALR1
      interacting with Trp2 of galanin and His264 of hGALR1 interacting with Tyr9 of
      galanin.

PMID- 11983933
TI  - Requirement for hydrophobic Phe residues in Pleurotus ostreatus proteinase A
      inhibitor 1 for stable inhibition.
AB  - Pleurotus ostreatus proteinase A inhibitor 1 (POIA1) has been shown to be unique
      among the various serine protease inhibitors in that its C-terminal region
      appears to be the reactive site responsible for its inhibitory action toward
      proteases. To investigate in more detail the mechanism of inhibition by POIA1, we
      have been studying its structural requirements for stable inhibition of
      proteases. In this study, we focused on hydrophobic Phe residues, which are
      generally located in the interior of protein molecules. A Phe-->Ala replacement
      at position 44 or 56 was introduced into a 'parent' mutant of POIA1 that had been
      converted into a strong and resistant inhibitor of subtilisin BPN' by replacement
      of its six C-terminal residues with those of the propeptide of subtilisin BPN'
      and the effects on inhibitory properties and structural stability were examined.
      Both of the mutated POIA1 molecules not only were found to exhibit decreased
      ability to bind to subtilisin BPN' (80-fold for the F44A mutant and 13-fold for
      the F56A mutant), but were also converted to temporary inhibitors that were
      degraded by the protease. The structural stability of the mutated POIA1 was also
      lowered, as shown by a 13 degrees C decrease in melting temperature for the F56A
      mutant. In particular, the F44A mutant was found to lose its tertiary structure,
      as judged from the circular dichroism spectrum, demonstrating that Phe44 is a
      strict requirement for structural formation by the POIA1 molecule. These results
      clearly indicate that stabilization of POIA1 by hydrophobic residues in its
      molecular interior is required for stable inhibition of the protease. This
      requirement for a stable tertiary structure is shared with other serine protease
      inhibitors, but other structural requirements seem to differ, in that strong
      binding with the protease is required for POIA1 whereas conformational rigidity
      around the reactive site is essential for many other protease inhibitors.

PMID- 11983934
TI  - Dehydrophenylalanine zippers: strong helix-helix clamping through a network of
      weak interactions.
AB  - A decapeptide Boc-L-Ala-(Delta Delta Phe)(4)-L-Ala-(Delta Delta Phe)3-Gly-OMe
      (Peptide I) was synthesized to study the preferred screw sense of consecutive
      alpha,beta-dehydrophenylalanine (Delta Delta Phe) residues. Crystallographic and
      CD studies suggest that, despite the presence of two L-Ala residues in the
      sequence, the decapeptide does not have a preferred screw sense. The peptide
      crystallizes with two conformers per asymmetric unit, one of them a slightly
      distorted right-handed 3(10)-helix (X) and the other a left-handed 3(10)-helix
      (Y) with X and Y being antiparallel to each other. An unanticipated and
      interesting observation is that in the solid state, the two shape-complement
      molecules self-assemble and interact with an extensive network of C-H...O
      hydrogen bonds and pi-pi interactions, directed laterally to the helix axis with
      amazing regularity. Here, we present an atomic resolution picture of the weak
      interaction mediated mutual recognition of two secondary structural elements and
      its possible implication in understanding the specific folding of the hydrophobic
      core of globular proteins and exploitation in future work on de novo design.

PMID- 11983935
TI  - Engineering a novel secretion signal for cross-host recombinant protein
      expression.
AB  - Protein secretion is conferred by a hydrophobic secretion signal usually located
      at the N-terminal of the polypeptide. We report here, the identification of a
      novel secretion signal (SS) that is capable of directing the secretion of
      recombinant proteins from both prokaryotes and eukaryotes. Secretion of fusion
      reporter proteins was demonstrated in Escherichia coli, Saccharomyces cerevisiae
      and six different eukaryotic cells. Estrogen-inducibility and secretion of fusion
      reporter protein was demonstrated in six common eukaryotic cell lines. The rate
      of protein secretion is rapid and its expression profile closely reflects its
      intracellular concentration of mRNA. In bacteria and yeast, protein secretion
      directed by SS is dependent on the growth culture condition and rate of
      induction. This secretion signal allows a flexible strategy for the production
      and secretion of recombinant proteins in numerous hosts, and to conveniently and
      rapidly study protein expression.

PMID- 11983936
TI  - Do defects in ion channel glycosylation set the stage for lethal cardiac
      arrhythmias?
AB  - Many ion channels are modified by the addition of carbohydrate residues. Fozzard
      and Kyle discuss evidence that sialic acid residues on glycosylated cardiac
      sodium and potassium channels may be important for preventing early after
      depolarizations that can result in cardiac arrhythmias.

PMID- 11983937
TI  - Opening Pandora's box: clinical data and the study of complex diseases.
AB  - Complex diseases have complex phenotypes, and proper diagnosis requires that the
      analysis take into account the patient's history and exposure to environmental
      factors, as well as genetic information. Signaling information is one aspect of a
      grander "biomedical informatics" approach advocated for a better understanding of
      a patient's medically relevant disease phenotype.

PMID- 11983938
TI  - Lethal weight loss: the focus shifts to signal transduction.
AB  - A hallmark of life-threatening disease in vertebrates is cachexia, a syndrome of
      weight loss with progressive erosion of body protein. Tumor necrosis factor (TNF)
      and other endogenously derived factors are sufficient to mediate the
      pathophysiology of cachexia in vivo, but the downstream signaling pathways have
      remained a mystery until recently. Tracey describes the involvement of the stress
      activated protein kinase p38 and the transcriptional regulators nuclear factor
      kappa B and peroxisome proliferator-activated receptor gamma coactivator-1 in
      causing alterations in myocytes and skeletal muscle physiology. Furthermore,
      soluble factors including TNF and proteolysis-inducing factor may enhance protein
      degradation through the ubiquitin-proteosome pathway.

PMID- 11983939
TI  - Harvesting cells under anchorage-independent cell transformation conditions for
      biochemical analyses.
AB  - Most molecular biology and biochemical analyses use cultured cells grown in
      anchorage-dependent monolayer conditions. The standard oncogenic transformation
      assay for cell lines is usually performed in soft agar rather than in monolayers
      because of the higher transformation efficiency of cells in soft agar. However,
      cells suspended in soft agar cannot be readily recovered for studying inducible
      biochemical and molecular events. We developed an over-agar assay that enables us
      to study tumor promoter-induced cell transformation and the associated
      biochemical or molecular events under anchorage-independent conditions.

PMID- 11983940
TI  - Standardized angiographically guided  over-dilatation  of stents using high
      pressure technique optimize results without increasing risks.
AB  - BACKGROUND: Routine angio-guided stent deployment results in a relatively high
      restenosis rate, which is mostly due to stent sub-expansion. Several different
      intravascular ultrasound (IVUS) criteria for optimal stent deployment have been
      proposed. A minimal in-stent restenosis and a minimal in-stent lumen area of > or
      = 9 mm2 have been associated with low rates of restenosis and target lesion
      revascularization (TLR) at 6 months. The role of high-pressure stent deployment
      and/or upsizing the post-dilatation balloon has not yet been clarified. The aim
      of this study was to evaluate the possibility of achieving accepted IVUS criteria
      safely without IVUS guidance with the combination of high-pressure deployment and
      post-dilatation with a 0.25 mm oversized balloon. METHODS: Thirty-four stents (26
      NIR, 3 AVE GFX, 3 ACS GFX, 1 Bard, 1 Jostent) were implanted in 30 patients until
      optimal angiographical results were obtained (< 10% residual stenosis visually).
      Forty percent of the patients had unstable angina pectoris, forty-four percent
      had complex lesions (B2 and C) and 29% were occlusions. Mean inflation pressure
      was 12.6 +/- 1.6 atm, mean stent diameter was 3.2+/- 0.4 mm and mean stent length
      was 15.1+/- 5.4 mm. Post-dilatation was performed with the same stent using a
      short (compared to the angiographic reference segment), 0.25 mm oversized Scimed
      Maxxum Energy 3.5 +/- 0.4 mm balloon using high pressure (16.1 +/- 1.7 atm)
      followed by an off-line IVUS examination of the stents. There was clinical follow
      up for 1 year. Results in patients with single-vessel disease were compared with
      those of non-randomized controls, who were stented with high pressure but without
      over-dilatation. RESULTS: No stent achieved the nominal diameter, in spite of
      over-dilatation. Mean minimal stent diameter (MLD) according to IVUS was 2.9 +/-
      0.4 mm (92% of the angiographic reference diameter). Mean minimal lumen area
      (MLA) was 7.7 +/- 2.2 mm2. An in-stent MLA > or = 90% of the distal reference
      segment (AVID criteria) and an MLA > or = 100% or > or = 90% of the
      smallest/average reference segment (MUSIC criteria) was found in 67% and 57%,
      respectively. MLA > or = 9 mm2 was achieved in 38%. All stents had good
      apposition and obtained a symmetry index > or = 0.7 mm. No acute perforations,
      dissections or other serious complications occurred during the over-dilatation.
      At 1 year, five patients had re-angina leading to a new coronary angiography;
      only 1 patient had a significant in-stent restenosis requiring re-PTCA. Compared
      to non-overdilated historical controls, the standardized over-dilatation seemed
      to give a larger MLD (3.0 +/- 0.4 mm vs. 2.7 +/- 0.4 mm; p = 0.03), more patients
      who fulfilled AVID criteria (70% vs. 32%; p = 0.048) and more stents with MLA >
      or = 9 mm2 (46% vs. 11%; p = 0.02). CONCLUSION: A standardized 0.25 mm over
      dilatation of stents never achieved nominal stent size, but did improve lumen
      gain and was associated with low target vessel revascularization without adding
      complications to the routine stenting procedure.

PMID- 11983941
TI  - A simple step towards better stent deployment.

PMID- 11983942
TI  - Angiopeptin-eluting stents: observations in human vessels and pig coronary
      arteries.
AB  - Local drug delivery from polymer-coated coronary stents may reduce the incidence
      of in-stent restenosis. Angiopeptin, an inhibitor of smooth muscle cell
      proliferation, may reduce the clinical impact of restenosis. The objectives of
      this study were to characterize the release kinetics and distribution of
      angiopeptin-loaded phosphorylcholine (PC)-coated drug delivery (DD) BiodivYsio
      stents and assess their safety and efficacy at reducing neointima formation. I125
      angiopeptin-loaded DD-PC-coated stents were implanted into human saphenous vein
      segments ex vivo, and I125 angiopeptin was detected in the medial layer at 1
      hour. When implanted in pig coronary arteries, I125 angiopeptin was found
      adjacent to the stent at intervals up to 28 days. No significant amounts were
      found elsewhere. To assess efficacy, twelve angiopeptin-loaded DD-PC-coated
      stents, twelve non-loaded DD-PC stents, ten standard PC-coated stents and 8
      uncoated stents were implanted into normal porcine coronary arteries. Stents were
      harvested at 28 days and neointima formation was assessed by computerized
      morphometry. No adverse tissue reactions were seen with any of the PC-coated
      stents. No significant differences were seen in neointimal or luminal cross
      sectional areas between study groups. Local delivery of I125 angiopeptin into the
      vascular wall can be achieved using a PC-coated stent. Delivery of angiopeptin
      from  drug delivery  PC-coated stents is safe, but does not lead to a significant
      reduction in neointimal growth at 28 days within the parameters of this study.

PMID- 11983943
TI  - Early and late clinical and angiographic outcomes following terumo coronary stent
      implantation.
AB  - The Terumo stent is a new, balloon-expandable, stainless-steel device with a
      unique multicellular design to provide robust radial force and end-stoppers to
      prevent dislodgement. We evaluated the early and late clinical and angiographic
      outcomes of Terumo coronary stent implantation in native coronary arteries using
      an open, nonrandomized 3-center registry. From July 1998 to June 1999, a total of
      118 Terumo stents were implanted in 105 patients (mean age, 58 +/- 10 years). A
      significant proportion of patients suffered from diabetes (34%), prior myocardial
      infarction (MI; 43%) and unstable angina (31%). Most target lesions (48%) had
      unfavorable morphological characteristics (type B2 or C); mean reference luminal
      diameter was 2.76 +/- 0.41 mm and lesion length was 11.4 +/- 5.3 mm. Primary
      success in stent deployment was achieved in 103 patients (98%). There was 1
      patient with acute stent thrombosis in whom 2 overlapping stents were deployed.
      Following stenting, the minimal luminal diameter increased from 1.04 +/- 0.48 mm
      to 2.39 +/- 0.33 mm. Six-month angiography was performed in 97 patients (92%),
      and the binary angiographic restenosis (> or = 50% narrowing) rate was 16%. Late
      loss index was 0.50 +/- 0.43. By 6 months, two patients (1.9%) died, two patients
      (1.9%) had Q-wave MI and 9 patients (8.4%) required repeat coronary
      interventions. Therefore, our study shows that the Terumo stent is potentially
      safe and efficacious in the treatment of coronary narrowings, even in the
      presence of unfavorable clinical conditions and complex lesion morphological
      characteristics.

PMID- 11983944
TI  - Clopidogrel treatment before percutaneous coronary intervention reduces adverse
      cardiac events.
AB  - OBJECTIVE: Platelet inhibition during percutaneous coronary intervention (PCI)
      generally reduces adverse cardiac events. There are very few data on the
      combination of aspirin and the platelet adenosine diphosphate-receptor inhibitor
      clopidogrel given before the intervention. DESIGN: In a non-randomized
      comparison, a total of 706 consecutive patients received clopidogrel 375 mg in
      addition to aspirin on the day before PCI. The control group consisted of 724
      consecutive PCI patients receiving only aspirin pre-treatment. RESULTS: The two
      groups were well balanced regarding baseline characteristics. Pre-treatment with
      clopidogrel reduced the in-hospital composite of death, myocardial infarction or
      urgent revascularization by 41% compared to the control (8.2% versus 4.8%,
      respectively; p = 0.010). This was due to a decreased incidence of myocardial
      infarction (7.2% versus 4.4%; p = 0.024) and percutaneous reintervention (1.2%
      versus 0.3%; p = 0.039). There was no difference in femoral complications between
      the groups. For every patient in the clopidogrel group, there was a cost
      reduction of SEK 447 ($40 United States currency). CONCLUSION: Clopidogrel
      treatment in addition to aspirin before PCI was associated with a reduction of in
      hospital adverse cardiac events. It was also safe and cost-saving.

PMID- 11983945
TI  - Use of clopidogrel loading, enoxaparin, and double-bolus eptifibatide in the
      setting of early percutaneous coronary intervention for acute coronary syndromes.
AB  - This study sought to evaluate the safety and feasibility of using the combination
      of aspirin, front-loaded clopidogrel, enoxaparin, and eptifibatide in patients
      with acute coronary syndromes immediately prior to percutaneous coronary
      intervention. One hundred ninety-eight patients (39 with acute myocardial
      infarction) received aspirin 325 mg orally, clopidogrel 300 mg orally, enoxaparin
      0.5 mg/kg intravenous (IV), and eptifibatide using the ESPIRIT dosing (180  g/kg
      bolus IV, immediately followed by a 2  g/kg/minute continuous IV infusion, and
      then a second 180  g/kg bolus IV ten minutes after the first bolus). A total of
      363 lesions were intervened; two were determined unsuccessful. Arterial sheaths
      were removed using manual compression after 3 hours. In the immediate follow-up,
      one patient developed rigors thought to be related to the eptifibatide therapy
      and a second patient experienced rebleeding at the access site. No other major
      bleeding or access-site hematomas were noted, and no patient developed
      thrombocytopenia. Over the subsequent 30 days, no episodes of acute vessel/stent
      thromboses were recognized. There were no deaths. Repeat coronary intervention
      was required in one patient at a previously untreated site. Clopidogrel was
      discontinued early in 5 patients due to rash. In conclusion, this pilot study
      demonstrates the feasibility of administering aspirin, clopidogrel, enoxaparin,
      and eptifibatide in the setting of percutaneous coronary intervention for acute
      coronary syndromes. These agents can be administered moments before the coronary
      intervention with no apparent compromise in patient safety.

PMID- 11983946
TI  - Optimized combination of antiplatelet treatment and anticoagulation for
      percutaneous coronary intervention: the final word is not out yet!

PMID- 11983947
TI  - Part II: risk stratification in patients with unstable angina and non-ST segment
      elevation myocardial infarction: evidence-based review.

PMID- 11983948
TI  - Aortic dissection complicating failed coronary stenting.
AB  - We present a case of coronary dissection with retrograde extension to the sinus
      of Valsalva and ascending aorta after transradial percutaneous coronary
      intervention. Sealing the entry port of the coronary dissection with a stent
      resulted in failure. We made careful observation of the patient s course because
      the dissection did not seem to progress. Abnormal staining of the false lumen
      disappeared within an hour and the dissection repaired itself spontaneously in a
      day.

PMID- 11983949
TI  - Unstable angina in a patient with a single sequential saphenous vein bypass graft
      supplying the entire coronary circulation.

PMID- 11983950
TI  - Endovascular treatment of carotid artery aneurysms with stent grafts.
AB  - Two patients with cervical carotid artery aneurysms were treated with stent
      grafts. Case report #1 was a 65-year-old male with aneurysm of the right internal
      carotid artery and recurrent transient ischemic attacks. Case report #2 describes
      a 64-year-old male with a pulsatile neck mass and persistent neck discomfort.
      Both patients underwent successful implantation of stent grafts with complete
      obliteration of the aneurysms and alleviation of symptoms. Case report #2 also
      underwent coil embolization of the right external carotid artery to prevent
      retrograde filling of the aneurysmal sac. Endovascular stent graft obliteration
      of carotid aneurysms appears safe, feasible and a less invasive option compared
      to surgical repair.

PMID- 11983951
TI  - Treatment of a giant coronary aneurysm with a novel technique: scaffolding
      (tunnel) stenting to support PTFE-covered stents: insights from intravascular
      ultrasound.
AB  - This report describes a patient with progressive angina and a giant coronary
      aneurysm in the right coronary artery. Percutaneous treatment was performed using
      a novel technique consisting of implantation of a long stent that provided 
      scaffolding  or bridge for the subsequent implantation of two
      polytetrafluoroethylene-covered stents. Complete closure of the aneurysm was
      successfully achieved. In the angiogram performed 3 months later for recurrent
      angina, a localized narrowing at the distal stent edge (corresponding to severe
      underexpansion of the stent struts on intravascular ultrasound) was observed.
      This was successfully treated with balloon angioplasty. The technical details of
      this new technique are described.

PMID- 11983952
TI  - Subclavian artery pseudoaneurysm   successful exclusion with a covered self
      expanding stent.
AB  - Subclavian pseudoaneurysms are rare clinical entities occurring most commonly
      after iatrogenic injury to the subclavian artery. The management of subclavian
      pseudoaneurysms remains a challenge because of their non-compressibility and
      close proximity to vital intra-thoracic structures. Until recently, the treatment
      of choice was surgical intervention. In this case report, an iatrogenic
      subclavian pseudoaneurysm was successfully managed using a covered, self
      expanding stent after an uncovered stent was unsuccessful in sealing the
      pseudoaneurysm.

PMID- 11983953
TI  - Obliteration of a left main coronary artery aneurysm with a PTFE-coated stent.
AB  - The successful percutaneous obliteration of a left main coronary artery aneurysm
      using a covered stent (JOMED) is described. The immediate angiographic result was
      excellent and the early post-procedural period was uneventful. Six-month follow
      up angiography revealed no changes.

PMID- 11983954
TI  - Spontaneous closure of a perforation-induced coronary artery pseudoaneurysm.
AB  - We describe an unusual case of a coronary perforation presenting as a large
      pseudoaneurysm. An elderly woman who had undergone percutaneous coronary
      intervention several months earlier presented with shortness of breath. Cardiac
      catheterization revealed a large pseudoaneurysm arising from the proximal
      circumflex artery. At follow-up angiography a few days later, the pseudoaneurysm
      had spontaneously closed. In the discussion, we describe the incidence and
      treatment of this rare complication.

PMID- 11983955
TI  - Rapid evolution from coronary dissection to pseudoaneurysm after stent
      implantation: a glimpse at the pathogenesis using intravascular ultrasound.
AB  - Coronary dissection during angioplasty can evolve into pseudoaneurysm. Stenting
      should prevent this complication. We present a case of coronary pseudoaneurysm
      after dissection that developed despite stent implantation. Intravascular
      ultrasound demonstrated no sealing of the false lumen due to undersizing and non
      apposition to the wall by the stent.

PMID- 11983956
TI  - Letting the air out of the follow-up balloon.

PMID- 11983957
TI  - A new quaternary thiophosphate, RbNb2(S2)3(PS4).
AB  - The structure of the new quaternary thiophosphate rubidium diniobium
      tris(disulfide) tetrathiophosphate, RbNb(2)(S2)(3)(PS4), is made up of one
      dimensional (infinity)(1)[Nb(2)(S2)(3)(PS4)(-)] chains along the [101] direction,
      and these chains are separated from one another by Rb(+) ions. The chain is
      basically built up from [Nb(2)S(12)] units and tetrahedral [PS(4)] groups. The
      [Nb(2)S(12)] units are linked together to form a linear [Nb(2)S(9)] chain by
      sharing the S-S prism edge. Short and long Nb-Nb distances [2.888 (2) and 3.760
      (2) A, respectively] alternate along the chain, and the anionic species S(2)(2-)
      and S(2-) are observed.

PMID- 11983958
TI  - Copper(II) hypophosphite: the alpha- and beta-forms at 270 and 100 K, and the
      gamma-form at 270 K.
AB  - Copper(II) hypophosphite has been shown to exist as several polymorphs. The
      crystal structures of monoclinic alpha-, orthorhombic beta- and orthorhombic
      gamma-Cu(H(2)PO(2))(2) have been determined at different temperatures. The
      geometry of the hypophosphite anion in all three polymorphs is very close to the
      idealized one, with point symmetry mm2. Despite having different space groups,
      the structures of the alpha- and beta-polymorphs are very similar. The polymeric
      layers formed by the Cu atoms and the hypophosphite ions, which are identical in
      the alpha- and beta-polymorphs, stack in the third dimension in different ways.
      Each hypophosphite anion is coordinated to three Cu atoms. On cooling, a minimum
      amount of contraction was observed in the direction normal to the layers. The
      structure of the polymeric layers in the gamma-polymorph is quite different.
      There are two symmetry-independent hypophosphite anions; the first is coordinated
      to two Cu atoms, while the second is coordinated to four Cu atoms. In all three
      polymorphs, the Cu atoms are coordinated by six O atoms of six hypophosphite
      anions, forming tetragonal bipyramids; in the alpha- and beta-polymorphs, there
      are four short and two long Cu-O distances, while in the gamma-polymorph, there
      are four long and two short Cu-O distances.

PMID- 11983959
TI  - AgNi3(PO4)(HPO4)2: an alluaudite-like structure.
AB  - The new title phosphate, silver trinickel phosphate bis(hydrogenphosphate), has
      been synthesized by the hydrothermal method. It has an alluaudite-like structure
      but shows some differences owing to the presence of the H atoms. The structure is
      isomorphous with the compounds of general formula AM(3)(XO(4))(HXO(4))(2) (A is
      Na or Ag, M is Co, Zn or Mn, and X is As or P), with the Ag atom, one Ni atom and
      one P atom lying on twofold axes.

PMID- 11983960
TI  - Tl2Te and its relationship with Tl5Te3.
AB  - The crystal structure of Tl(2)Te, dithallium telluride, has been determined by
      single-crystal X-ray diffraction. The analysis of the structure shows that this
      compound is the first known representative of a new crystal structure type. The
      structural relationship with the related Tl(5)Te(3) phase is discussed.

PMID- 11983961
TI  - Bis(ammonium) fluorophosphate at room temperature.
AB  - The title room-temperature phase of (NH(4))(2)(PO(3)F) is orthorhombic (Pna2(1))
      and is related to the beta-K(2)SO(4) structure family. The title structure
      consists of ammonium cations, NH(4)(+), and fluorophosphate anions, (PO(3)F)(2-).
      These ions are connected by N-H.O hydrogen bonds. Two-centre N-H.F hydrogen bonds
      are not present in the structure. Phase transitions were detected at 251+/-2 and
      274+/-2 K during cooling and heating, respectively.

PMID- 11983962
TI  - gamma-Sodium gallate: a Rietveld refinement using X-ray powder diffraction.
AB  - Tetrahedrally coordinated oxides usually present polymorphism, but for NaGaO(2),
      only the beta polymorph has been reported. In this work, the synthesis and
      structural characterization of gamma-sodium gallate, gamma-NaGaO(2), are
      presented. The crystal structure belongs to the orthorhombic system, space group
      Pbca (No. 61), and has been characterized by a Rietveld refinement of the X-ray
      powder diffraction pattern. The structure is similar to those exhibited by the
      gamma phases of many tetrahedral oxides.

PMID- 11983963
TI  - trans-(2-Acetylpyridine-kappa2N,O)dichlorobis(dimethyl sulfoxide
      kappaS)ruthenium(II).
AB  - In the title complex, [RuCl(2)(C(7)H(7)NO)(C(2)H(6)OS)(2)], the metal ion is at
      the centre of a distorted octahedral NOCl(2)S(2) coordination sphere. The neutral
      2-acetylpyridine ligand binds to the metal ion through the pyridine N and
      carbonyl O atoms, forming a five-membered chelate ring. The monodentate S
      coordinating dimethyl sulfoxide molecules are mutually cis, and the two remaining
      positions in the coordination sphere are occupied by two mutually trans Cl(-)
      ions.

PMID- 11983964
TI  - Comparison of two polymeric transition metal complexes with 1,4
      benzenedicarboxylate ions as bridging ligands, [Co(C8H4O4)(C12H8N2)(H2O)] and
      [Cu(C8H4O4)(C10H9N3)].H2O.
AB  - The title complexes, catena-poly[[aqua(1,10-phenanthroline
      kappa(2)N,N')cobalt(II)]-micro-benzene-1,4-dicarboxylato-kappa(2)O(1):O(4)],
      [Co(C(8)H(4)O(4))(C(12)H(8)N(2))(H(2)O)], (I), and catena-poly[[[(di-2-pyridyl
      kappaN-amine)copper(II)]-micro-benzene-1,4-dicarboxylato
      kappa(4)O(1),O(1'):O(4),O(4')] hydrate], [Cu(C(8)H(4)O(4))(C(10)H(9)N(3))].H(2)O,
      (II), take the form of zigzag chains, with the 1,4-benzenedicarboxylate ion
      acting as an amphimonodentate ligand in (I) and a bis-bidentate ligand in (II).
      The Co(II) ion in (I) is five-coordinate and has a distorted trigonal-bipyramidal
      geometry. The Cu(II) ion in (II) is in a very distorted octahedral 4+2
      environment, with the octahedron elongated along the trans O-Cu-O bonds and with
      a trans O-Cu-O angle of only 137.22 (8) degrees.

PMID- 11983965
TI  - A three-dimensional CuII-WIV bimetallic porous assembly containing a zigzag
      ladder structure.
AB  - The asymmetric unit of the three-dimensional Cu(II)-W(IV) polymeric assembly
      [Cu(en)(2)][Cu(en)][W(CN)(8)].4H(2)O](n) (en is ethylenediamine, C(2)H(8)N(2)) or
      [Cu(2)W(CN)(8)(C(2)H(8)N(2))(3)].4H(2)O](n), which can be named as polymeric
      bis(ethylenediamine)copper(II) (ethylenediamine)copper(II) octacyanotungstate(IV)
      tetrahydrate or penta-micro-cyano
      tricyanotris(ethylenediamine)dicopper(II)tungsten(IV) tetrahydrate, consists of
      two half [Cu(en)(2)](2+) cations (Cu(2+) on inversion centres), a [Cu(en)](2+)
      cation and a [W(CN)(8)](4-) ion, together with four water molecules. The latter
      Cu(II) site is coordinated by five N atoms from an en ligand and by three
      cyanides in a distorted square-pyramidal geometry. The Cu(II) atoms of the two
      [Cu(en)(2)](2+) cations reside in an elongated octahedral coordination
      environment, and one of them is localized at a centre of inversion. The W atom is
      coordinated by eight cyano groups in an irregular square antiprism. Five of these
      act as bridging units connecting the W and the three Cu atoms, to form an
      infinite three-dimensional porous network containing a zigzag ladder structure.

PMID- 11983966
TI  - Polymeric aqua(nitrilotriacetato)erbium(III).
AB  - In the structure of the title compound, [Er(C(6)H(6)NO(6))(H(2)O)](n), the Er
      atoms are eight-coordinated by one N atom and six O atoms from three symmetry
      related nitrilotriacetate (NTA) ligands, and by one O atom of a water molecule,
      adopting a distorted square-antiprismatic geometry. The Er atoms are linked by
      the NTA ligands into layers, which are interconnected via O-H.O hydrogen bonds
      between the water molecules and the carboxylate O atoms. The asymmetric unit
      contains one Er atom, one NTA ligand and one water molecule, all of which are
      located in general positions.

PMID- 11983967
TI  - trans-Bis[3-(2-fluorophenyl)-1-(4-nitrophenyl)triazenido-kappaN3]bis(pyridine
      kappaN)palladium(II).
AB  - In the title complex, [Pd(C(12)H(8)FN(4)O(2))(2)(C(5)H(5)N)(2)] or trans
      [Pd(FC(6)H(4)N=N-NC(6)H(4)NO(2))(C(5)H(5)N)(2)], the Pd atom lies on a centre of
      inversion in space group P-1. The coordination geometry about the Pd(2+) ion is
      square planar, with two deprotonated 3-(2-fluorophenyl)-1-(4
      nitrophenyl)triazenide ions, FC(6)H(4)N=N-NC(6)H(4)NO(2)(-), acting as
      monodentate ligands (two-electron donors), while two neutral pyridine molecules
      complete the metal coordination sphere. The whole triazenide ligand is not
      planar, with the largest interplanar angle being 16.8 (5) degrees between the
      phenyl ring of the 2-fluorophenyl group and the plane defined by the N=N-N
      moiety. The Pd-N(triazenide) and Pd-N(pyridine) distances are 2.021 (3) and 2.039
      (3) A, respectively.

PMID- 11983968
TI  - catena-Poly[[bis(cis-1-tert-butyltetrazole-kappaN4)copper(II)]-di-micro-chloro].
AB  - The title polymeric compound, [CuCl(2)(C(5)H(10)N(4))(2)](n), is the first
      structurally characterized complex with a bulky 1-alkyltetrazole ligand. The
      coordination polyhedron of the Cu atom is an elongated octahedron. The equatorial
      positions of the octahedron are occupied by the two Cl atoms, with Cu-Cl
      distances of 2.2920 (8) and 2.2796 (9) A, and by the two N-4 atoms of the
      tetrazole ligands, with Cu-N distances of 2.023 (2) and 2.039 (2) A. Two symmetry
      related Cl atoms occupy the axial positions, at distances of 2.8244 (8) and
      3.0174 (8) A from the Cu atom. The [CuCl(2)(C(5)H(10)N(4))(2)] units form
      infinite chains extended along the b axis, linked together only by van der Waals
      interactions. The skeleton of each chain consists of Cu and Cl atoms.

PMID- 11983969
TI  - Tetrakis(5-tert-butylpyrazole-1kappaN2)tetrachloro-1kappaCl,2kappa3Cl-micro-oxo
      1:2kappa2O-diiron(III).
AB  - The title compound, [Fe(2)Cl(4)O(C(7)H(12)N(2))(4)], contains vertex-sharing
      distorted tetrahedral [FeOCl(3)](-) and octahedral [FeOCl(Hpz(t)Bu)(4)](+)
      moieties (Hpz(t)Bu is 5-tert-butylpyrazole), linked by a bent oxo bridging
      ligand. The two Fe(III) centres are also bridged by intramolecular hydrogen bonds
      between the pyrazole N-H groups and the O(2-) and Cl(-) ligands.

PMID- 11983970
TI  - Tetrakis(micro-benzothiazole-2-thiolato)-1:2kappa4N:S2;1:2kappa4S2:N-dichloro
      1kappaCl,2kappaCl-dirhenium(III)(Re-Re) dichloromethane solvate: a bridged
      complex with a long Re-Re quadruple bond.
AB  - The title compound, [Re(2)(C(7)H(4)NS(2))(4)Cl(2)].CH(2)Cl(2), consists of
      dirhenium molecules with bridging N,S-benzothiazole-2-thiolate ligands, axial Cl(
      ) ligands and intramolecular hydrogen bonding. These molecules adopt somewhat
      staggered conformations, with a long Re-Re quadruple bond distance of 2.2716 (3)
      A.

PMID- 11983971
TI  - Tetraaquatetrakis(trimethylphosphine oxide-kappaO)cerium(III) trichloride
      trihydrate.
AB  - The title compound, [Ce(C(3)H(9)OP)(4)(H(2)O)(4)]Cl(3).3H(2)O, contains eight
      coordinate Ce atoms in an approximate dodecahedral arrangement, with Ce-O(P) =
      2.372 (2)-2.423 (2) A and Ce-O(H(2)) = 2.518 (2)-2.630 (2) A.

PMID- 11983972
TI  - Pentacarbonyl[tris[4-(methylsulfonyl)phenyl]stannyl]manganese(I): an unexpected
      tetragonal structure.
AB  - The title compound, [MnSn(C(7)H(7)O(2)S)(3)(CO)(5)], is asymmetric but
      crystallizes in the highly symmetric tetragonal space group I-4. This is achieved
      without the need for any disorder, either around the Sn atom or in any of the
      methylsulfonyl groups. The environment around the Sn atom has the following
      geometry: Sn-Mn = 2.6564 (7) A, mean Sn-C = 2.175 (5) A, mean C-Sn-C = 103 (2)
      degrees and mean C-Sn-Mn = 115 (6) degrees. The crystal packing is assisted by
      weak Sn.O interactions between adjacent columns of molecules, with the resulting
      geometry at Sn approaching highly distorted trigonal-bipyramidal.

PMID- 11983973
TI  - Dichlorobis(2-methylquinoline N-oxide-kappaO)zinc(II) from powder data.
AB  - The crystal structure of the title compound, [ZnCl(2)(C(10)H(9)NO)(2)], has been
      determined from laboratory powder diffraction data. Although the powder pattern
      was initially indexed with tetragonal unit-cell dimensions, the correct solution
      was found in an orthorhombic space group using a combination of grid-search and
      simulated-annealing techniques. The subsequent bond-restrained Rietveld
      refinement gave bond lengths and angles within expected ranges. The molecule has
      crystallographically imposed twofold symmetry.

PMID- 11983974
TI  - Pentachloro-1,3,6-tris(diethylphenylphosphino)dirhenium(II,III).
AB  - The title complex [systematic name: pentachloro-1kappa(3)Cl,2kappa(2)Cl
      tris(diethylphenylphosphino)-1kappaP,2kappa(2)P-dirhenium(II,III)(Re-Re)], 1,3,6
      Re(2)Cl(5)(PEt(2)Ph)(3) or [Re(2)Cl(5)(C(10)H(15)P)(3)], consists of dirhenium
      molecules with eclipsed structures similar to those of previously characterized
      1,3,6-Re(2)Cl(5)(PR(3))(3) compounds. The Re-Re bond distance is 2.2262 (3) A and
      the metal-metal bond order is 3.5.

PMID- 11983975
TI  - [2,6-Bis[(dimethylamino-kappaN)methyl]phenyl-kappaC]iodopalladium(II)
      bis(diiodine).
AB  - The distorted square-planar coordination environment of the palladium(II) centre
      in [Pd(NCN)I].2I(2) [NCN is 2,6-bis[(dimethylamino)methyl]phenyl, C(12)H(19)N(2)]
      is defined by the monoanionic terdentate NCN ligand and one iodide anion. Two
      neutral I(2) molecules interact with the coordinated iodide anion at distances of
      approximately 3.3 A, suggesting an alternative description of the title compound
      as a palladium pentaiodide complex, i.e. [Pd(NCN)I(5)]. Weaker interactions of
      approximately 3.6 A between the I(5)(-) anions link the complexes into a two
      dimensional network.

PMID- 11983976
TI  - Intermolecular interactions in cyanodimethylarsine and cyanodimethylstibine.
AB  - Cyanodimethylarsine, [As(CH(3))(2)(CN)], and cyanodimethylstibine,
      [Sb(CH(3))(2)(CN)], have closely related, but not isomorphous, crystal structures
      containing XCN.XCN. chains. The N. As distance of 3.185 (3) A is slightly shorter
      than the expected van der Waals distance of 3.5 A, while the N.Sb distance of
      2.862 (9) A, compared with the expected value of 3.7 A, is much shorter. This is
      consistent with Sb being a stronger Lewis acid than As.

PMID- 11983977
TI  - Multiple bridging modes in a novel trinuclear titanium 1,3-dioxypropane compound,
      Ti3(methyliminodiethanolate)2(1,3-propanediolate)4.
AB  - The title compound, bis(2,2'-methyliminodiethanolato)
      1kappa(3)O,N,O';3kappa(3)O,N,O'-di-micro(3)-propane-1,3-diolato
      1:2:3kappa(8)O:O,O':O'-micro-propane-1,3-diolato-1:3kappa(2)O:O'-propane-1,3
      diolato-2kappa(2)O,O'-trititanium(IV),
      [Ti(3)(C(5)H(11)NO(2))(2)(C(3)H(6)O(2))(4)], has four 1,3-propanediolate ligands
      binding in three different modes. Two ligands chelate adjacent Ti atoms with
      normal micro(3)-O bridges, giving typical edge-sharing of the Ti distorted
      octahedra, one chelating to the central Ti atom with no micro-bridging, and the
      other spanning the cluster, binding only to the outermost Ti atoms. The two
      methyliminodiethanolate ligands each coordinate to the outer Ti atoms via their N
      and two O atoms. The Ti-O bond lengths range, in a self-consistent fashion, from
      1.816 (2) to 2.082 (2) A, while the average Ti-N distance is 2.391 (3) A.

PMID- 11983978
TI  - Enantiomeric bis(micro-N,N'-hexamethylenedisalicylaldiminato)dicopper(II)
      complexes.
AB  - The title dimeric complex, bis[micro-2,2'-[hexane-1,6
      diylbis(nitrilomethylidyne)]diphenolato
      1:2kappa(4)O,N:N',O']dicopper(II),[Cu(2)(C(20)H(22)N(2)O(2))(2)], has been
      investigated by single-crystal X-ray diffraction, by thermogravimetric analysis
      and differential scanning calorimetry, and also by FT-IR spectroscopy. Different
      synthetic and crystallization procedures gave crystals which were quite different
      in appearance, and it was initially thought that these were different polymorphic
      forms. Subsequent structure determination showed, in fact, serendipitous
      preparation of crystals in the P4(1) space group by one method and in space group
      P4(3) by the other. In these enantiomorphic structures, the Cu atoms have a
      distorted flattened tetrahedral coordination, with Cu-N and Cu-O distances in the
      ranges 1.954 (4)-1.983 (4) and 1.887 (4)-1.903 (4) A, respectively.

PMID- 11983979
TI  - (eta3-Allyl-2kappa3C)(chloro-1kappaCl)(micro-N,N'-diethyldithioxamidato
      1:2kappa4S,S':N,N')[diphenyl(2-pyridyl)phosphine
      1kappaP]palladium(II)platinum(II) chloroform solvate.
AB  - The title compound, [PdPtCl(C(3)H(5))(C(6)H(10)N(2)S(2))(C(17)H(14)NP)].CHCl(3),
      was obtained by deprotonation of the initial platinum(II) complex of the
      dithioxamide and subsequent reaction with [Pd(eta(3)-C(3)H(5))(micro-Cl)](2).
      Both metal atoms exhibit a square-planar coordination geometry, with the two
      planes forming a dihedral angle of 21.7 (2) degrees. The dithioxamide bis
      chelating bridge is flat.

PMID- 11983980
TI  - Dichlorobis(1-propylimidazolidine-2-thione-kappaS)cobalt(II).
AB  - The crystal structure of the title compound, [CoCl(2)(C(6)H(12)N(2)S)(2)],
      consists of monomer units of a Co(II) atom coordinated to two 1
      propylimidazolidine-2-thione ligands and to two chloride ions. The heterocyclic
      thione ligand is monodentate and coordinated to the metal through the thione S
      atom. The environment around the Co(II) atom is a slightly distorted tetrahedron.
      The Co-S bond lengths are 2.341 (2) and 2.330 (2) A, and the Co-Cl bond lengths
      are 2.234 (2) and 2.238 (2) A. The most important point of distortion is the S-Co
      S bond angle of only 97.83 (8) degrees. Intramolecular classical hydrogen bonds
      are found between the chloride ions and the N-H groups. Additionally, intra- and
      intermolecular non-classical hydrogen bonds are found.

PMID- 11983981
TI  - (+)-2-(1,2,3,4,4a,5,6,7-Octahydro-4a,8-dimethyl-7-oxo-2-naphthyl)propionic acid:
      catemeric hydrogen bonding in a bicyclic sesquiterpenoid keto acid.
AB  - The title compound, C(15)H(22)O(3), derived from a naturally occurring
      sesquiterpenoid, has two molecules in the asymmetric unit, differing principally
      in the rotational conformation of the carboxyl group. Each species aggregates
      separately as a carboxyl-to-ketone hydrogen-bonding catemer [O.O = 2.752 (4) and
      2.682 (4) A, and O-H.O = 161 (4) and 168 (4) degrees ], producing two
      crystallographically independent single-strand hydrogen-bonding helices, with
      opposite end-to-end orientations, passing through the cell in the b direction.
      Three intermolecular C-H.O=C close contacts exist for the ketone.

PMID- 11983982
TI  - Arene-arene stacking in the revised structure of 2,2'-bipyridinium
      hexafluorophosphate.
AB  - The title compound, C(10)H(9)N(2)(+).PF(6)(-), crystallizes in space group
      P2(1)/c in a supercell doubled along b, rather than in the previously reported
      polar space group Pc [Milani, Anzilutti, Vicentini, Santi, Zangrando, Geremia &
      Mestroni (1997). Organometallics, 16, 5064-5075]. This new structure
      determination provides a more appropriate description of intra- and
      intermolecular parameters. The crystal packing is dominated by shifted pi-stacked
      arrangements of adjacent aromatic moieties.

PMID- 11983983
TI  - 2-[1-(Phenylsulfonyl)ethyl]benzoic acid and 2-[1-(phenylsulfonyl)propyl]benzoic
      acid.
AB  - In the title acids, C(15)H(14)O(4)S, (I), and C(16)H(16)O(4)S, (II),
      respectively, the angle between the planes of the benzene ring and the carboxyl
      group is 13.7 (1) degrees for (I) and 21.3 (1) degrees for (II). The molecular
      structures are stabilized by intramolecular C-H.O hydrogen bonds. The crystal
      packing is stabilized by a single O-H.O hydrogen bond in both compounds, in which
      the O and H atoms are ordered; H.O 1.87 A for (I) and 1.83 A for (II), O.O 2.680
      (2) A for (I) and 2.652 (3) A for (II), and O-H.O 172 degrees for (I) and 175
      degrees for (II). The hydrogen bond forms a cyclic dimer, with graph-set
      descriptor R(2)(2)(8), about a centre of symmetry.

PMID- 11983984
TI  - 4-Methoxyphenylphosphonic acid: reactivity of Lawesson's reagent.
AB  - The title compound, C(7)H(9)O(4)P, obtained as a by-product of the reaction
      between Lawesson's reagent, (I), and CH(3)I, can be recognized as the final
      product of the S/O interchange reaction at the P atom of (I). Hydrogen bonds of
      type P-O-H.O=P link molecules into helical chains and form ten-membered hydrogen
      bonded rings with the graph-set notation R(3)(2)(10). Weaker intermolecular
      contacts between P-O and a phenyl H atom link the chains into a three-dimensional
      lattice. The parent benzenephosphonic acid [Weakley (1976). Acta Cryst. B32, 2889
      2890] does not adopt an analogous structure, but its arsenic analogue [Shimada
      (1960). Bull. Chem. Soc. Jpn, 33, 301-304] does and can be regarded as
      isostructural. We rationalize these three structures in terms of their
      significant intermolecular interactions.

PMID- 11983985
TI  - Di-2-pyridyl ketone p-aminobenzoylhydrazone hydrate.
AB  - The title compound [systematic name: 4-amino-2'-(di-2
      pyridylmethylene)benzohydrazide hydrate], C(18)H(15)N(5)O.H(2)O, crystallizes in
      the triclinic space group P-1. Structural analysis shows one pyridine ring and
      the p-aminobenzoylhydrazone moiety to be coplanar and orthogonal to the second
      pyridine ring. The packing reveals infinite molecular units interlocked via a
      network of hydrogen bonds.

PMID- 11983986
TI  - Ethyl 6-acetylamino-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylate.
AB  - The title compound, C(20)H(21)NO(3), is a derivative of Aib (alpha
      aminoisobutyric acid) and is cyclized at the C(alpha) position by biphenyl rings.
      The seven-membered ring possesses C2 symmetry. The C(alpha) cyclization causes
      the backbone to assume a helical conformation in the crystal structure. The
      packing of the molecules is stabilized by intermolecular C-H.O, C-H.pi and N-H.O
      hydrogen bonds.

PMID- 11983987
TI  - Pseudophomins A and B, a class of cyclic lipodepsipeptides isolated from a
      Pseudomonas species.
AB  - The crystal structures of pseudophomins A and B, with primary structures beta
      hydroxydecanoyl-L-Leu-D-Glu-D-allo-Thr-D-Ile-D-Leu-D-Ser-L-Leu-D-Ser-L-Ile
      monohydrate, C(55)H(97)N(9)O(16).H(2)O, and beta-hydroxydodecanoyl-L-Leu-D-Glu-D
      allo-Thr-D-Ile-D-Leu-D-Ser-L-Leu-D-Ser-L-Ile monohydrate,
      C(57)H(101)N(9)O(16).H(2)O, new cyclic lipodepsipeptides isolated from
      Pseudomonas fluorescens strain BRG100, have been solved. The absolute
      configuration of pseudophomin A has been determined from anomalous dispersion and
      the stereochemistry of the beta-hydroxy acid group is R.

PMID- 11983988
TI  - N,N',N",N"'-Tetraethylterephthalamidinium bis(tetrazolate).
AB  - The crystal structure of the title 2:1 salt of tetrazole and a substituted
      terephthalamidine, C(16)H(28)N(4)(2+).2CHN(4)(-), contains an infinite network of
      hydrogen bonds, with short N.N distances of 2.820 (2) and 2.8585 (19) A between
      the tetrazolate anion and the amidinium cation. Involvement of the lateral N
      atoms of the tetrazole in the hydrogen bonding appears to be a typical binding
      pattern for the tetrazolate anion.

PMID- 11983989
TI  - Reactive intermediates in peptide synthesis: the N-oxysuccinimido ester of Nalpha
      para-toluenesulfonyl-alpha-aminoisobutyric acid.
AB  - The preparation, characterization, and molecular and crystal structures of
      succinimido 2-(tosylamino)isobutyrate, C(15)H(18)N(2)O(6)S, are described. The
      succinimido ring is nearly orthogonal to the ester group.

PMID- 11983990
TI  - Ethyl beta-[2-[4-(dimethylamino)phenyliminomethyl]-1-(phenylsulfonyl)indol-3
      yl]acrylate.
AB  - The title compound, C(28)H(27)N(3)O(4)S, crystallizes in the centrosymmetric
      space group P2(1)/n, with one molecule in the asymmetric unit. In the indole
      ring, the dihedral angle between the fused rings is 3.6 (1) degrees. The phenyl
      ring of the sulfonyl substituent makes a dihedral angle of 79.2 (1) degrees with
      the best plane of the indole moiety. The phenyl ring of the dimethylaminophenyl
      group is orthogonal to the phenyl ring of the phenylsulfonyl group. The dihedral
      angle formed by the weighted least-squares planes through the pyrrole ring and
      the phenyl ring of the dimethylaminophenyl group is 7.8 (1) degrees. The
      molecular structure is stabilized by C-H.O and C-H.N interactions.

PMID- 11983991
TI  - 5,5-Dimethyl-2-[6-methyl-2-(methylsulfanyl)pyrimidin-4-yloxy]-1,3,2
      dioxaphosphorinane-2-thione.
AB  - The title compound, C(11)H(17)N(2)O(3)PS(2), is a cyclic thiophosphoryl
      pyrimidine derivative exhibiting insecticidal properties. The crystal structure
      determination gives evidence for the presence of the thione isomer of the
      compound. The pyrimidine nucleus is planar and its substituents have small
      deviations from the least-squares plane. The dioxaphosphorinane ring adopts a
      chair conformation. The lack of classical hydrogen bonds and the weak
      intermolecular interactions lead to a 'loose' packing characterized by channels
      in the structure.

PMID- 11983992
TI  - Secondary interactions in 4-bromo-N,N-dimethylanilinium bromide.
AB  - The crystal packing of the title compound, C(8)H(11)BrN(+).Br(-), involves three
      types of secondary interaction: a classical N-H.Br(-) hydrogen bond, a 'weak' but
      short C-H.Br(-) interaction (normalized H.Br distance of 2.66 A) and a cation
      anion Br.Br contact of 3.6331 (4) A. The hydrogen bonds connect two cations and
      two anions to form rings of graph set R(4)(2)(14). The Br.Br contacts link these
      rings to form layers parallel to the bc plane.

PMID- 11983994
TI  - 1-Acetyl-3'-(4-bromophenyl)-3'-chlorospiro[3H-indole-3,2'-oxetan]-2(1H)-one.
AB  - In the title compound, C(18)H(13)BrClNO(3), the heterocyclic ring of the indole
      is distorted from planarity towards an envelope conformation. The orientations of
      the indole, oxetane, chloro and bromophenyl substituents are conditioned by the
      sp(3) states of the spiro-junction and the Cl-attached C atoms.

PMID- 11983993
TI  - 4-Amino-6-benzyloxy-2-(methylsulfanyl)-5-nitrosopyrimidine: hydrogen-bonded
      dimers linked into pi-stacked chains.
AB  - The title compound, C(12)H(12)N(4)O(2)S, crystallizes with Z' = 2 in space group
      P2(1)/c. The intramolecular dimensions are consistent with a highly polarized
      electronic structure. Each of the independent molecules forms a centrosymmetric
      dimer linked by paired N-H.N hydrogen bonds, and these dimers are linked into a
      single type of chain by aromatic pi-pi-stacking interactions.

PMID- 11983995
TI  - Hydrogen bonding in 2-amino-4,6-dimethoxypyrimidine, 2-benzylamino-4,6
      bis(benzyloxy)pyrimidine and 2-amino-4,6-bis(N-pyrrolidino)pyrimidine: chains of
      fused rings and a centrosymmetric dimer.
AB  - Molecules of 2-amino-4,6-dimethoxypyrimidine, C(6)H(9)N(3)O(2), (I), are linked
      by two N-H.N hydrogen bonds [H.N 2.23 and 2.50 A, N.N 3.106 (2) and 3.261 (2) A,
      and N-H.N 171 and 145 degrees ] into a chain of fused rings, where alternate
      rings are generated by centres of inversion and twofold rotation axes. Adjacent
      chains are linked by aromatic pi-pi-stacking interactions to form a three
      dimensional framework. In 2-benzylamino-4,6-bis(benzyloxy)pyrimidine,
      C(25)H(23)N(3)O(2), (II), the molecules are linked into centrosymmetric
      R(2)(2)(8) dimers by paired N-H.N hydrogen bonds [H.N 2.13 A, N.N 2.997 (2) A and
      N-H.N 170 degrees ]. Molecules of 2-amino-4,6-bis(N-pyrrolidino)pyrimidine,
      C(12)H(19)N(5), (III), are linked by two N-H.N hydrogen bonds [H.N 2.34 and 2.38
      A, N.N 3.186 (2) and 3.254 (2) A, and N-H.N 163 and 170 degrees ] into a chain of
      fused rings similar to that in (I).

PMID- 11983996
TI  - 9-Cyano-10-methylacridinium hydrogen dinitrate.
AB  - The title compound, C(15)H(11)N(2)(+).HN(2)O(6)(-), crystallizes in the
      monoclinic space group C2/c with four molecules in the unit cell. The planar 9
      cyano-10-methylacridinium cations lie on crystallographic twofold axes and are
      arranged in layers, almost perpendicular to the ac plane, in such a way that
      neighbouring molecules are positioned in a 'head-to-tail' manner. These cations
      and the hydrogen dinitrate anions are linked through C-H.O interactions involving
      four of the six O atoms of the anion and the H atoms attached to the C atoms of
      the acridine moiety in ring positions 2 and 4. The H atom of the hydrogen
      dinitrate anion appears to be located on the centre of inversion relating two of
      the four O atoms engaged in the above-mentioned C-H.O interactions. In this way,
      columns of either anions or cations running along the c axis are held in place by
      the network of C-H.O interactions, forming a relatively compact crystal lattice.

PMID- 11983997
TI  - C-H...pi and pi--pi interactions in the supramolecular structure of 3-methyl-1,4
      diphenyl-1H-pyrazolo[3,4-b]pyridine.
AB  - The supramolecular structure of the title compound, C(19)H(15)N(3), is defined by
      pi-pi-stacking and C-H.pi interactions. There are no conventional hydrogen bonds
      in the structure.

PMID- 11983998
TI  - Three isomeric bis(methoxycarbonyl)[2.2]paracyclophanes.
AB  - The title isomers 4,16- (pseudo-ortho), 4,15- (pseudo-gem) and 4,12
      bis(methoxycarbonyl)[2.2]paracyclophane (pseudo-para), C(20)H(20)O(4), all show
      the typical structural features of [2.2]paracyclophanes (flattened boat
      conformation of the rings, lengthened single bonds in the bridges and narrow ring
      angles at the bridgehead atoms). The 4,12-isomer displays crystallographic
      inversion symmetry. The carbonyl groups adopt a conformation in which they are
      directed away from the ring systems towards the nearest bridge; the corresponding
      angle at the ring substituent atom is widened. Crystal packing involves C-H.pi
      interactions for the 4,15-isomer and weak C-H.O hydrogen bonds for the other two
      isomers.

PMID- 11983999
TI  - The molecular and supramolecular structures of four 1,5,6,10b
      tetrahydropyrazolo[1,5-c]quinazolines.
AB  - The supramolecular structures of the title compounds, 2-phenyl-5-p-tolyl
      1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline, C(23)H(21)N(3), (I), 5-(4
      bromophenyl)-2-phenyl-1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline,
      C(22)H(18)BrN(3), (II), 2-(4-chlorophenyl)-5-phenyl-1,5,6,10b
      tetrahydropyrazolo[1,5-c]quinazoline, C(22)H(18)ClN(3), (III), and 5-(4
      bromophenyl)-2-(4-chlorophenyl)-1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline,
      C(22)H(17)BrClN(3), (IV), are of two general types. Compounds (I), (II) and (III)
      form base-paired dimers via N-H.N hydrogen bonds, where (I) and (II) are
      isomorphous, while in (IV), there are no conventional hydrogen bonds.

PMID- 11984000
TI  - Reactive oxygen-induced carcinogenesis causes hypermethylation of p16(Ink4a) and
      activation of MAP kinase.
AB  - BACKGROUND: Implantation of foreign materials into mice and humans has been noted
      to result in the appearance of soft tissue sarcomas at the site of implantation.
      These materials include metal replacement joints and Dacron vascular grafts. In
      addition, occupational exposure to nickel has been shown to result in an
      increased risk of carcinogenesis. The molecular mechanisms of foreign body
      induced carcinogenesis are not fully understood. MATERIALS AND METHODS: In order
      to gain insight into these mechanisms, we implanted nickel sulfide into wild type
      C57BL/6 mice as well as a mouse heterozygous for the tumor suppressor gene, p53.
      Malignant fibrous histiocytomas arose in all mice, and we have characterized the
      profile of tumor suppressor genes and signal transduction pathways altered in
      these cells. RESULTS: All tumors demonstrated hypermethylation of the tumor
      suppressor gene p16, as well as activation of the mitogen activated protein
      kinase (MAP kinase) signaling pathway. This knowledge may be beneficial in the
      prevention and treatment of tumors caused by foreign body implantation.
      CONCLUSIONS: Oxidative stress induced by nickel sulfide appears to cause loss of
      p16 and activation of MAP kinase signaling. These findings support the hypothesis
      of synergistic interactions between MAP kinase activation and p16 loss in
      carcinogenesis.

PMID- 11984001
TI  - Influenza virus infection is not affected by serum amyloid P component.
AB  - BACKGROUND: Binding of serum amyloid P component (SAP) to its ligands, including
      bacteria, chromatin and amyloid fibrils, protects them from degradation, is anti
      opsonic and anti-immunogenic. SAP thereby enhances the virulence of pathogenic
      bacteria to which it binds. However SAP also contributes to host resistance
      against bacteria to which it does not bind. Human SAP has been reported to bind
      to the influenza virus and inhibit viral invasion of cells in tissue culture. We
      therefore investigated a possible role of SAP in either host resistance or viral
      virulence during influenza infection in vivo. MATERIALS AND METHODS: The clinical
      course of mouse adapted influenza virus infection, the host antibody response,
      and viral replication, were compared in wild type mice, mice with targeted
      deletion of the SAP gene, and mice transgenic for human SAP. The effects of
      reconstitution of SAP deficient mice with pure human SAP, and of a drug that
      specifically blocks SAP binding in vivo, were also studied. Binding of mouse and
      human SAP to immobilized influenza virus was compared. RESULTS: The presence,
      absence, or availability for binding of SAP in vivo had no significant or
      consistent effect on the course or outcome of influenza infection, or on either
      viral replication or the anti-viral antibody response. Mouse SAP bound much less
      avidly than human SAP to influenza virus. CONCLUSIONS: In marked contrast to the
      dramatic effects of SAP deficiency on host resistance to different bacterial
      infections, mouse SAP apparently plays no significant role during infection of
      mice with influenza virus. Human SAP binds much more avidly than mouse SAP to the
      virus, but also had no effect on any of the parameters measured and is therefore
      unlikely to be involved in human influenza infection.

PMID- 11984002
TI  - Association of severe noncerebral Plasmodium falciparum malaria in Brazil with
      expressed PfEMP1 DBL1 alpha sequences lacking cysteine residues.
AB  - BACKGROUND: Cytoadherence and rosetting contribute to the development of severe
      Plasmodium falciparum malaria. In Brazil,severe falciparum malaria is mostly
      associated with renal or pulmonary complications and very rarely with cerebral
      malaria. The most N-terminal DBL1 alpha domain of PfEMP1, a protein encoded by
      the var multigene family mediates rosetting. We analyzed parasites of Brazilian
      patients with severe malaria to determine whether there were particular DBL1
      alpha var sequences predominantly expressed in such patients. MATERIALS AND
      METHODS: DBL1 alpha var sequences were obtained from parasites of Brazilian
      patients with severe and mild malaria and were analyzed by standard bioinformatic
      programs. Three hundred twenty var DBL1 alpha sequences obtained from 80
      Brazilian patients with mild malaria were spotted in high-density filters and
      hybridized to probes representing predominantly expressed sequences in parasites
      from patients with severe malaria. A DBL1 alpha domain was expressed in bacteria
      and used to demonstrate its binding capacity to erythrocytes by
      immunofluorescence. RESULTS: Forty-three different and unreported DBL1 alpha
      amino acid sequences were obtained. Sequences predominantly expressed in patients
      with severe malaria could be subgrouped due to deletions of 1-2-cysteine
      residues. These sequences were commonly found in the var gene repertoire of
      parasites from patients with mild malaria, yet they were rarely expressed in
      these patients. A recombinant protein representing the most abundantly expressed
      sequence detected in one patient with severe malaria bound directly to uninfected
      erythrocytes. CONCLUSIONS: This is the first report showing an association of
      severe noncerebral malaria from Brazil with particular DBL1 alpha sequences.

PMID- 11984003
TI  - The dual AngII/AVP receptor gene N119S/C163R variant exhibits sodium-induced
      dysfunction and cosegregates with salt-sensitive hypertension in the Dahl salt
      sensitive hypertensive rat model.
AB  - BACKGROUND: Essential hypertension is a prevalent complex polygenic disease and a
      major risk factor for cardiovascular disease, the leading cause of death in
      developed countries. Because of its complex and multifactorial nature, its
      genetic determinants still remain largely unknown. The Dahl salt-sensitive
      hypertensive rat model exhibits impaired sodium handling, which is hypothesized
      to play a key role in the pathophysiology of polygenic hypertension. Thus, genes
      associated with renal regulation of salt and water balance are a priori likely
      candidates for a causative role in hypertension pathogenesis. The functional
      properties and renal-specific expression of the recently characterized AngII/AVP
      receptor suggest a putative modulator role in tubular sodium and fluid
      reabsorption. Based on these observations, we investigated the potential
      involvement of the AngII/AVP receptor in salt-sensitive hypertension. MATERIALS
      AND METHODS: We performed cosegregation analysis of the AngII/AVP receptor locus
      with salt-sensitive hypertension in an F2 (Dahl S X Dahl salt-resistant [R])
      hybrid male cohort characterized for blood pressure by radiotelemetry after 8
      weeks of high salt challenge. Further molecular analysis was done to identify
      putative AngII/AVP receptor molecular variants that could account for the AngII/
      AVP receptor involvement in salt-sensitive hypertension pathogenesis. RESULTS:
      The AngII/AVP receptor was mapped to rat chromosome 1, 1.7 cM centromeric to the
      D1Rat188 marker by radiation hybrid mapping analysis. Quantitative trait locus
      (QTL) analysis detected a highly significant linkage of the AngII/AVP receptor
      locus with high blood pressure (LRS = 13.8, p= 0.0002). Molecular
      characterization of the Dahl S and Dahl R AngII/AVP receptor cDNAs revealed two
      amino acid substitutions in the Dahl S AngII/AVP receptor (N119S, C163R) when
      compared to the Dahl R AngII/AVP receptor. These mutations are associated with an
      increased receptor affinity for both ligands (AVP and AngII) and an enhanced G(s)
      coupling by the receptor resulting in increased activation of adenylate cyclase
      with concomitant increase in cAMP production. CONCLUSIONS: The observed molecular
      dysfunction in the Dahl S AngII/AVP receptor is consistent with increased tubular
      sodium and fluid reabsorption observed in Dahl S rats. Interestingly, the
      AngII/AVPr locus is within the narrowed chromosome 1 QTL region for blood
      pressure detected in different rat intercross linkage analyses. Altogether, the
      data strongly suggest that the AngII/AVP receptor is a hypertension
      susceptibility gene in the Dahl S rat model, as well as raises the hypothesis
      that it too underlies the chromosome 1 blood pressure QTL identified in other
      hypertension rat models.

PMID- 11984004
TI  - Identification of two novel elements involved in human MUCI gene expression in
      vivo.
AB  - BACKGROUND: MUC1, a membrane-tethered glycoprotein that is expressed on a number
      of epithelial cell types in vivo, is over-expressed in adenocarcinomas and
      thought to play a significant role in tumour progression and metastasis. Hence,
      elucidation of the mechanisms of regulation of MUC1 gene expression is of
      considerable biological importance. Our aim was to evaluate regulation of MUC1
      expression in vivo. MATERIALS AND METHODS: DNase I hypersensitive sites (DHS)
      were mapped in chromatin from human cell lines and human MUC1 transgenic mice.
      MUC1 expression was evaluated by RT-PCR and Northern blots. RESULTS: We
      identified two novel DHS in the MUC1 promoter at -750 bp and -250 bp from the
      transcriptional start site. These DHS were detected in human cell lines and in a
      human MUC1 transgene in mice. The -750 DHS was apparent in many cell types
      irrespective of the level of MUC1 expression but the -250 DHS was only evident in
      cells that express MUC1 and its intensity correlated with the abundance of MUC1
      transcripts. The -250 DHS became undetectable in cell lines representing a
      transition from colon adenoma to carcinoma, commensurate with a significant
      reduction in MUC1 expression. CONCLUSIONS: The -750 and -250 regions are
      conserved between the human MUC1 and mouse Muc1 genes and may be associated with
      functionally important genetic elements. The DHS at -250 is in the vicinity of
      previously defined purine/pyrimidine mirror repeat elements that may form
      intramolecular H-DNA structures, which can alter the accessibility of chromatin
      to regulatory proteins.

PMID- 11984005
TI  - Identification and functional characterization of a human GalNAc [alpha]2,6
      sialyltransferase with altered expression in breast cancer.
AB  - BACKGROUND: We sought to identify genes with altered expression during human
      breast cancer progression by applying mRNA comparisons of normal and tumor
      mammary cell lines with increasingly malignant phenotypes. The gene encoding a
      new sialyltransferase (STM) was found to be down-regulated in tumor cells.
      Abnormal expression and enzymatic activities of sialyltransferases in tumor cells
      result in the formation of tumor-associated carbohydrate antigens that can be
      used for the better understanding of the disease process and are applied for
      tumor diagnosis and immunotherapy. Altered glycosylation patterns of the MUC1
      mucin, in particular, is a target antigen for immunotherapy of breast and other
      cancers. MATERIALS AND METHODS: Total RNAs from multiple normal mammary
      epithelial cell strains and tumor cell lines were compared by differential
      display and the differential expression of selected cDNAs was confirmed by
      Northern analyses. Recombinant STM was expressed in COS-7 cells. The substrate
      and linkage specificity of STM was examined using various oligosaccharides and O
      glycosylated proteins as acceptor substrates. The chromosomal localization of the
      SIATL1 gene was assigned by somatic cell hybrid analysis. RESULTS: A human
      sialyltransferase gene was identified by differential display as being down
      regulated in breast tumor cell lines as compared to normal mammary epithelial
      cell strains, and the corresponding full-length cDNA (stm) was cloned. The
      encoded protein of 374 amino acid residues contained the L- and S-sialylmotifs,
      two catalytic regions conserved in all functional sialyltransferases. Recombinant
      STM is an active GalNAc alpha2,6-sialyltransferase with Gal beta 1,3 GalNAc-O
      Ser/Thr and (+/- Neu5Ac alpha 2,3) Gal beta 1,3GalNAc-O-Ser/Thr acceptor
      specificity. The SIATL1 gene, encoding STM, was mapped to the long arm of human
      chromosome 17 at q23-qter, a region that is nonrandomly deleted in human breast
      cancers. However, Southern analyses indicated that SIATL1 is usually not grossly
      rearranged in breast tumors. Northern analyses showed that the gene was widely
      expressed in normal human tissues, as well as in normal breast and prostate
      epithelial cell lines, but significantly down-regulated or absent in
      corresponding tumor cell lines. CONCLUSIONS: Our findings suggest that aberrant
      expression of STM sialyltransferase in tumors could be a feature of the malignant
      phenotype. In breast cancers, the MUC1 mucin is overexpressed and contains
      shorter O-glycans as compared to the normal mucin. Because STM catalyzes the
      synthesis of O-glycans, cloning and characterization of its substrate specificity
      will contribute to the understanding of the molecular mechanisms underlying the
      aberrant glycosylation patterns of O-glycans and the formation of mucin-related
      antigens in human breast cancers.

PMID- 11984007
TI  - Arrhythmic and sudden death in chronic ischemic heart disease--a review of
      epidemiological data.

PMID- 11984006
TI  - The Chediak-Higashi protein interacts with SNARE complex and signal transduction
      proteins.
AB  - BACKGROUND: Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency
      disease characterized by giant lysosomes and impaired leukocyte degranulation.
      CHS results from mutations in the lysosomal trafficking regulator (LYST) gene,
      which encodes a 425-kD cytoplasmic protein of unknown function. The goal of this
      study was to identify proteins that interact with LYST as a first step in
      understanding how LYST modulates lysosomal exocytosis. MATERIALS AND METHODS:
      Fourteen cDNA fragments, covering the entire coding domain of LYST, were used as
      baits to screen five human cDNA libraries by a yeast two-hybrid method, modified
      to allow screening in the activation and the binding domain, three selectable
      markers, and more stringent confirmation procedures. Five of the interactions
      were confirmed by an in vitro binding assay. RESULTS: Twenty-one proteins that
      interact with LYST were identified in yeast two-hybrid screens. Four
      interactions, confirmed directly, were with proteins important in vesicular
      transport and signal transduction (the SNARE-complex protein HRS, 14-3-3, and
      casein kinase II). CONCLUSIONS: On the basis of protein interactions, LYST
      appears to function as an adapter protein that may juxtapose proteins that
      mediate intracellular membrane fusion reactions. The pathologic manifestations
      observed in CHS patients and in mice with the homologous mutation beige suggest
      that understanding the role of LYST may be relevant to the treatment of not only
      CHS but also of diseases such as asthma, urticaria, and lupus, as well as to the
      molecular dissection of the CHS-associated cancer predisposition.

PMID- 11984008
TI  - Prevention of cardiac arrest: risk assessment after myocardial infarction.

PMID- 11984009
TI  - Primary prevention in chronic ischemic heart disease.

PMID- 11984010
TI  - Arrhythmias associated with dilated cardiomyopathy.

PMID- 11984011
TI  - Arrhythmias and sudden death in hypertrophic cardiomyopathy.

PMID- 11984012
TI  - Risk assessment in hypertrophic cardiomyopathy.

PMID- 11984013
TI  - Prognosis of patients with hypertrophic cardiomyopathy in Japan.

PMID- 11984014
TI  - Arrhythmias, sudden death and syncope in hypertensive cardiovascular disease.

PMID- 11984015
TI  - Arrhythmias in patients with congenital heart disease.

PMID- 11984016
TI  - The Brugada syndrome.

PMID- 11984017
TI  - ECG phenomenon of idiopathic and paradoxical short QT intervals.

PMID- 11984018
TI  - Update of arrhythmogenic right ventricular dysplasia.

PMID- 11984019
TI  - Congenital Long QT syndrome.

PMID- 11984020
TI  - Idiopathic left ventricular tachycardia: clinical features, mechanisms and
      management.

PMID- 11984021
TI  - Right ventricular outflow tract tachycardia: an update.

PMID- 11984022
TI  - Arrhythmogenic right ventricular cardiomyopathy caused by a deletion in
      plakoglobin (Naxos disease).

PMID- 11984023
TI  - Familial polymorphic ventricular tachycardia--intracellular calcium channel
      disorder.

PMID- 11984024
TI  - Idiopathic ventricular tachycardias in infants and children.

PMID- 11984025
TI  - Catecholaminergic polymorphic ventricular tachyarrhythmias in children.

PMID- 11984026
TI  - Perioperative arrhythmias: incidence, risk assessment, evaluation, and
      management.

PMID- 11984027
TI  - The young competitive athlete with cardiovascular abnormalities: causes of sudden
      death, detection by preparticipation screening, and standards for
      disqualification.

PMID- 11984028
TI  - Arrhythmic sudden cardiac death due to coronary artery spasm.

PMID- 11984029
TI  - Coronary artery anomalies and sudden death.

PMID- 11984030
TI  - Myocardial bridging: does it cause sudden death?

PMID- 11984031
TI  - Arrhythmias associated with Chagas' heart disease.

PMID- 11984032
TI  - Cardiac arrhythmias in the elderly.

PMID- 11984033
TI  - Mitral valve prolapse and cardiac arrhythmias.

PMID- 11984034
TI  - Arrhythmias associated with neuromuscular disorders.

PMID- 11984035
TI  - Arrhythmias occurring during pregnancy.

PMID- 11984036
TI  - Cardiac transplantation and pacemakers: when and what to implant.

PMID- 11984037
TI  - Arrhythmias in systemic sclerosis and related disorders.

PMID- 11984038
TI  - Arrhythmias and risk assessment in patients with renal failure.

PMID- 11984039
TI  - Cardiopulmonary resuscitation in dialysis patients.

PMID- 11984040
TI  - Sudden death in children with restrictive cardiomyopathy.

PMID- 11984041
TI  - Arrhythmias associated with cocaine abuse.

PMID- 11984042
TI  - Alternative medicine--boom or bust?

PMID- 11984043
TI  - Cardiac tumors that cause arrhythmias.

PMID- 11984045
TI  - The Quiet Professionals of Advances.

PMID- 11984046
TI  - Preparing for Another Innovative Conference.

PMID- 11984047
TI  - The AHCPR clinical practice guidelines, a decade later.

PMID- 11984048
TI  - Calciphylaxis: identification and wound management.

PMID- 11984049
TI  - Development of a severity scale for evaluating the need for Graftskin in
      nonhealing venous ulcers.
AB  - OBJECTIVE: To construct an easy-to-use severity scale based on data from a
      multicenter venous leg ulcer trial to predict which wounds will progress toward
      closure and which will remain unhealed. DESIGN: Factors that have an impact on
      wound healing (eg, ulcer duration, depth, area, location, and fibrin) were
      identified in the literature. A severity scale was constructed based on these
      factors. SETTING: Multicenter clinical trial. PATIENTS: 240 patients with venous
      leg ulcers of longer than 1 month's duration. MAIN RESULTS: Wound duration and
      area were identified as having the greatest impact on ulcer healing. Using
      multivariate regression analyses, a wound score of 8 or less was considered mild
      to moderate. A severe wound, having a score of 9 or greater, was found to be
      unlikely to heal with compression therapy alone. CONCLUSION: This severity scale
      can serve as an adjunctive tool in the prompt identification of ulcers with a
      poor healing prognosis and enable early intervention with alternate therapies. To
      optimize the severity scale, future trials should incorporate a method to review
      the interaction of known factors that impair wound healing.

PMID- 11984050
TI  - The cost of illness of pressure ulcers in The Netherlands.
AB  - OBJECTIVE: To conduct a cost-of-illness study of pressure ulcers in the
      Netherlands for different care settings, including home care, nursing homes,
      general hospitals, and university hospitals. DESIGN: A cost-of-illness study was
      conducted based on prevalence figures and expert opinion. A differential cost
      study approach was used, distinguishing among the 4 stages of pressure ulcer
      severity and the different care settings. To obtain expert opinion, structured
      interviews were conducted with pressure ulcer experts who were chosen randomly
      from the membership of the Dutch Society of Pressure Ulcer Experts. Information
      was gathered on volume of care parameters for each pressure ulcer stage,
      including personnel, extra days of care, and use of special beds and medical
      materials. Experts were asked to estimate the percentage of patients for which
      each care parameter was considered relevant; low and high estimates of each
      figure were given to determine the range of the calculations. Cost estimates were
      obtained from Dutch guidelines for cost calculations in health care, then
      converted to US dollars. SETTING: Home care, nursing homes, general hospitals,
      and university hospitals in the Netherlands. PARTICIPANTS: Experts on pressure
      ulcer management working in the different care settings. MAIN OUTCOME MEASURE:
      Cost-of-illness of pressure ulcers, converted to US dollars. MAIN RESULTS: The
      cost-of-illness of pressure ulcers ranged from a low estimate of $362 million to
      a high estimate of $2.8 billion. The most conservative estimate is approximately
      1% of the total Dutch health care budget. CONCLUSION: The cost-of-illness of
      pressure ulcers in the Netherlands is considerable.

PMID- 11984052
TI  - New Wound Care Codes for 2002.

PMID- 11984053
TI  - Evaluating and managing bite wounds.

PMID- 11984054
TI  - Measuring height and weight.

PMID- 11984055
TI  - Seizing the Opportunities for Wound Healing.

PMID- 11984063
TI  - Amifostine in clinical oncology: current use and future applications.
AB  - Amifostine (Ethyol), an inorganic thiophosphate, is a selective broad-spectrum
      cytoprotector of normal tissues that provides cytoprotection against ionizing
      radiation and chemotherapeutic agents, thus preserving the efficacy of
      radiotherapy and chemotherapy. This review summarizes the preclinical data and
      clinical experience with amifostine, and provides insight into future clinical
      directions. Amifostine, an inactive pro-drug, is transformed to an active thiol
      after dephosphorylation by alkaline phosphatase found in the normal endothelium.
      The absence of alkaline phosphatase in the tumoral endothelium and stromal
      components, and the hypovascularity and acidity of the tumor environment, may
      explain its cytoprotective selectivity. The cytoprotective mechanism of
      amifostine is complicated, involving free radical scavenging, DNA protection and
      repair acceleration, and induction of cellular hypoxia. Intravenous
      administration of amifostine 740-900 mg/m(2) before chemotherapy and 250-350
      mg/m(2) before each radiotherapy fraction are widely used regimens. The US Food
      and Drug Administration has approved the use of amifostine as a cytoprotector for
      cisplatin chemotherapy and for radiation-induced xerostomia. Ongoing trials are
      being conducted to determine the efficacy of amifostine in reducing radiation
      induced mucositis and other toxicities. Novel schedules and routes of
      administration are under investigation, and may further simplify the use of
      amifostine and considerably broaden its applications.

PMID- 11984064
TI  - The role of DNA repair in nitrogen mustard drug resistance.
AB  - The nitrogen mustards are an important class of DNA cross-linking agents, which
      are utilized in the treatment of many types of cancer. Unfortunately, resistance
      often develops in the treatment of patients and the tumor either never responds
      to or becomes refractory to these agents. Resistance to the nitrogen mustards in
      murine and human tumor cells has been reported to be secondary to alterations in
      (i) the transport of these agents, (ii) their reactivity, (iii) apoptosis and
      (iv) altered DNA repair activity. In the present review, we will discuss the role
      of DNA repair in nitrogen mustard resistance in cancer. The nitrogen mustards'
      lethality is based on the induction of DNA interstrand cross-links (ICLs). Two
      DNA repair pathways are known to be involved in removal of ICLs: non-homologous
      DNA end-joining (NHEJ) and Rad51-related homologous recombinational repair (HRR).
      The reports discussed here lead us to hypothesize that low NHEJ activity defines
      a hypersensitive state, while high NHEJ activity, along with increased HRR
      activity, contributes to the resistant state in chronic lymphocytic leukemia.
      Studies on human epithelial tumor cell lines suggest that HRR rather than NHEJ
      plays a role in nitrogen mustard sensitivity.

PMID- 11984065
TI  - Perindopril: possible use in cancer therapy.
AB  - Since angiogenesis is essential for the growth of any solid tumor, emerging
      efforts are being made to develop antiangiogenic therapy. To date, however, no
      antiangiogenic agent has become widely available for the clinical setting.
      Angiotensin I-converting enzyme (ACE) inhibitors are commonly used as
      antihypertensive agents and it has recently been suggested that they decrease the
      risk of cancer. Studies have found that an ACE inhibitor, perindopril, is a
      potent inhibitor of experimental tumor development and angiogenesis at a
      clinically comparable dose. The potent angiogenic factor, vascular endothelial
      growth factor (VEGF), is significantly suppressed by perindopril and also
      inhibits VEGF-induced tumor growth. In vitro studies showed that perindopril is
      not cytotoxic to either tumor cells or endothelial cells. Since perindopril is
      already in widespread clinical use without serious side effects, it may represent
      a potential new strategy for anticancer therapy.

PMID- 11984066
TI  - Immunotherapy of tumors with vaccines based on xenogeneic homologous molecules.
AB  - This review summarizes and discusses a new vaccine strategy based on xenogeneic
      homologous molecules by the breaking of immune tolerance against the growth
      factors or their receptors associated with tumor growth in a cross-reaction
      between the xenogeneic homologs and self-molecules. The xenogeneic vaccine may
      circumvent the fact that few tumor-specific antigens have been identified in
      human solid tumors and that the host usually shows immune tolerance to self
      molecules as antigens. It may be of importance for the further exploration of the
      applications of xenogeneic homologous genes identified in human and other animal
      genome sequence projects in cancer therapy.

PMID- 11984067
TI  - Vacuolar H(+)-ATPase: functional mechanisms and potential as a target for cancer
      chemotherapy.
AB  - Tumor cells in vivo often exist in a hypoxic microenvironment with a lower
      extracellular pH than that surrounding normal cells. Ability to upregulate proton
      extrusion may be important for tumor cell survival. Such microenvironmental
      factors may be involved in the development of resistant subpopulations of tumor
      cells. In solid tumors, both intracellular and extracellular pH differ between
      drug-sensitive and -resistant cells, and pH appears critical to the therapeutic
      effectiveness of anticancer agents. Four major types of pH regulators have been
      identified in tumor cells: the sodium-proton antiporter, the bicarbonate
      transporter, the proton-lactate symporter and proton pumps. Understanding
      mechanisms regulating tumor acidity opens up novel opportunities for cancer
      chemotherapy. In this minireview, we describe the structure and function of
      certain proton pumps overexpressed in many tumors--vacuolar H(+)-ATPases--and
      consider their potential as targets for cancer chemotherapy.

PMID- 11984068
TI  - Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12),
      collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type
      plasminogen activator, and diminish invasion and migration of human malignant and
      endothelial cell lines.
AB  - Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at
      therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13
      and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen
      activator (uPA), a serine proteinase and a pro-MMP activator. Dose-dependent
      inhibition was shown by three independent MMP assays. The inhibition was reduced
      in the presence of an increased concentration of Ca(2+) when compared to
      physiologic Ca(2+) concentration. Alendronate inhibited the in vitro invasion
      (Matrigel) of human HT1080 fibrosarcoma and C8161 melanoma cells, and the random
      migration of these malignant and endothelial cell lines capable of expressing
      MMPs and uPA. The concentration of alendronate required to inhibit 50% of the
      activity (IC(50)=40-70 microM) of MMPs corresponded to the IC(50) of down
      regulation of in vitro invasion and migration. The ability of bisphosphonates to
      down-regulate the in vitro invasion and random migration was comparable or
      slightly better in relation to the selective gelatinase inhibitor CTTHWGFTLC
      peptide. Alendronate but not CTTHWGFTLC peptide promoted the adhesion of HT1080
      fibrosarcoma and C8161 melanoma cell lines on fibronectin. Bisphosphonates are
      broad-spectrum MMP inhibitors and this inhibition involves cation chelation.
      Bisphosphonates further exert antimetastatic, anti-invasive and cell adhesion
      promoting properties, which may prevent metastases not only into hard tissues but
      also to soft tissues.

PMID- 11984069
TI  - The doxorubicin cardioprotective agent dexrazoxane (ICRF-187) induces
      endopolyploidy in rat neonatal myocytes through inhibition of DNA topoisomerase
      II.
AB  - Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin-induced
      cardiotoxicity, is also a potent catalytic inhibitor of DNA topoisomerase II. In
      this study we showed that dexrazoxane inhibited the division of neonatal rat
      ventricular myocytes in culture, and resulted in nuclear multilobulation
      (demonstrated by three-dimensional reconstruction of confocal images) and marked
      increases in nuclear size and DNA ploidy levels (as shown by flow cytometry). It
      was concluded that dexrazoxane interfered with cell division in cardiac myocytes
      by virtue of its ability to inhibit topoisomerase II.

PMID- 11984070
TI  - Biochemical and molecular effects of UCN-01 in combination with 5
      fluorodeoxyuridine in A431 human epidermoid cancer cells.
AB  - Concurrent and pre-exposure of A431 human epidermoid cancer cells to UCN-01, an
      investigational anticancer drug, with 5-fluoro--2'-deoxyuridine (FdUrd), which
      targets thymidylate synthase, produced more than additive cytotoxicty. A 24-h
      exposure to 10 nM FdUrd led to inhibition of TS, a 2.5-fold increase in total
      thymidylate synthase protein content, profound dTTP depletion and a 6.3-fold
      increase in the ratio of dATP to dTTP, but did not cause single-strand breaks in
      DNA. However, FdUrd enhanced UCN-01-associated DNA strand breaks. Concurrent
      thymidine exposure led to repletion of dTTP pools, and cytoprotection against
      FdUrd alone and with UCN-01. UCN-01 arrested cells in G1, decreased the
      percentage of FdUrd-treated cells in S phase and reduced FdUrd-DNA incorporation,
      suggesting the latter was not important for cytotoxicity. Delayed induction of
      high molecular mass DNA fragmentation and poly(ADP-ribose) polymerase cleavage
      was observed with the combination of UCN-01 and FdUrd. These findings suggest
      that while FdUrd-mediated deoxynucleotide imbalance alone was insufficient to
      induce apoptosis in this p53-mutant cell line, it magnified UCN-01's effects,
      most likely by interfering with DNA repair. The clinical evaluation of UCN-01
      combined with 5-fluoropyrimidines may be of interest.

PMID- 11984071
TI  - The effect of DNA-alkylating agents on gene expression from two integrated
      reporter genes in a mouse mammary tumor line.
AB  - A model system was developed to investigate the effects of DNA alkylating agents
      on cellular gene expression. The cytomegalovirus immediate-early promoter (CMV)
      and the mouse mammary tumor virus promoter (MMTV) were coupled separately to the
      luciferase reporter gene and stably expressed in cultured cells. The change in
      luciferase activity was used as a measure of gene expression inhibition. Seven
      well-characterized DNA alkylating agents of varied DNA adduct-forming ability
      were evaluated in this system. The major groove binders/intercalators (that form
      guanine adducts) increased CMV-luciferase activity above background, while minor
      groove binders (that form adenine adducts) all decreased it. The MMTV-luciferase
      activity was remarkably different to the CMV-luciferase activity and was
      inhibited to the greatest extent by the minor groove alkylators. One of these, a
      polybenzamide with spatially separated alkylating groups, inhibited gene
      expression to a greater extent than inhibition of general DNA or RNA synthesis.

PMID- 11984072
TI  - Role of gamma-glutamyltranspeptidase on the response of poorly and moderately
      differentiated rhabdomyosarcoma cell lines to buthionine sulfoximine-induced
      inhibition of glutathione synthesis.
AB  - Glutathione (GSH) is involved in many cellular functions, including cell growth
      and differentiation. GSH also plays an important role in the protection of cells
      against oxidative damage and hence in determining the sensitivity of cells to the
      cytotoxicity of anticancer agents. Because of this, induction of GSH depletion
      has been proposed as a good strategy for sensitizing tumor cells to antitumor
      agents. The aim of the present work is to study the effect of buthionine
      sulfoximine (BSO, a specific cellular GSH-depleting agent) in two rat tumor cell
      lines derived from the same rhabdomyosarcoma tumor model, the moderately
      differentiated and low metastatic F21 cell line, and the poorly differentiated
      and high metastatic S4MH cell line, to investigate the influence of the degree of
      differentiation in the induction of GSH depletion-based therapy. We observed
      that, whereas in the S4MH cell line BSO induced a dose-dependent inhibition of
      both cell growth in vitro and tumorigenic potential in vivo, in F21 cells the
      administration of moderate doses of BSO enhanced tumor growth and only at high
      doses was there a slight reduction of their tumorigenic potential. These effects
      were in consonance with the fact that the activity of gamma
      glutamyltranspeptidase (gamma-GT) present in the F21 cells was 4 times higher
      than in the S4MH cells. Indeed, inhibition of gamma-GT activity by acivicin not
      only abrogated the BSO-induced increase of GSH content and of cell growth, but
      also the combination of acivicin + BSO significantly decreased intracellular GSH
      levels and cell proliferation, and induced F21 cells to apoptosis. These studies
      suggest that, as occurs in the rhabdomyosarcoma tumor model, gamma-GT levels and
      the degree of differentiation of tumor cells might influence the response of
      tumor cells to inducers of GSH depletion, and should be taken into account in
      therapies based on GSH metabolism.

PMID- 11984073
TI  - Arsenic trioxide as a novel anticancer agent against human transitional carcinoma
      -characterizing its apoptotic pathway.
AB  - Arsenic trioxide (As(2)O(3)) has been shown to be an active agent against acute
      promyelocytic leukemia. Little is known about its therapeutic efficacy in human
      transitional carcinomas. In this study, the arsenic-mediated apoptotic pathway in
      transitional carcinoma cells was investigated. Three bladder transitional
      carcinoma cell lines were used, including a parental sensitive line and two
      resistant daughter lines (cisplatin and As(2)O(3) resistant). The As(2)O(3)
      mediated cytotoxicity to the three cell lines was studied in vitro in the
      presence or absence of buthionine sulfoximine (BSO), a chemotherapy modulator. In
      results, although a lesser extent of apoptosis was seen in cells treated with
      As(2)O(3) alone, more significant apoptotic events were observed in the combined
      treatment of As(2)O(3) and non-toxic concentrations of BSO (up to 10 microM).
      These included the accumulation of sub-G(1) fractions and internucleosomal DNA
      breakdown, which were preceded by production of reactive oxygen species, loss of
      mitochondrial membrane potential and activation of caspase-3. In conclusion,
      As(2)O(3) in the presence of BSO may be an active agent against both chemonaive
      and cisplatin-resistant transitional carcinomas. The As(2)O(3)-mediated
      cytotoxicity appeared to go through the conventional apoptotic pathway. Our
      results have clinical implications and warrant further investigation.

PMID- 11984074
TI  - Synthesis of a novel phosphatidylcholine conjugated to docosahexaenoic acid and
      methotrexate that inhibits cell proliferation.
AB  - Here we report the synthesis and characterization of a lipophilic
      phosphatidylcholine containing the omega-3 fatty acid docosahexaenoic acid (DHA)
      and the cytotoxic drug methotrexate (MTX). This novel phospholipid combines the
      fatty acid's and the drug's anticancer activities in a molecule amenable to a
      liposome bilayer for safe, simultaneous delivery of the two agents. Two
      phosphatidylcholines were synthesized, from 1-stearoyl or 1-docosahexaenoyl, 2
      hydroxy-sn-glycero-3-phosphocholine, to contain MTX in the sn-2 position and
      either stearic acid or DHA in the sn-1 position. The products contain fatty acid,
      MTX and phosphorus (1:1:1), and the MTX was released by phospholipase A(2),
      consistent with the proposed phospholipid structure. The predominant product
      linked MTX to the glycerol moiety through MTX's gamma-carboxyl group. Liposomes
      composed of 1-stearoyl, 2-oleoyl phosphatidylcholine plus 1-stearoyl, 2-oleoyl
      phosphatidylethanolamine and various concentrations of the novel phospholipids
      caused dose-dependent inhibition of murine leukemia cell proliferation in
      culture. The DHA- and MTX-containing phosphatidylcholine was more effective than
      that containing stearic acid, and DHA appeared to synergize with MTX when they
      were added as free agents or covalently linked in the phospholipid. These data
      show the feasibility of synthesizing, and the inhibitory activity of
      phosphatidylcholine with DHA in the sn-1 position and MTX in the sn-2 position,
      and suggest the compound's potential use in cancer chemotherapy.

PMID- 11984075
TI  - The antiproliferative and immunotoxic effects of L-canavanine and L-canaline.
AB  - L-Canavanine and its arginase-catalyzed metabolite, L-canaline, are two novel
      anticancer agents in development. Since the immunotoxic evaluation of agents in
      development is a critical component of the drug development process, the
      antiproliferative effects of L-canavanine and L-canaline were evaluated in vitro.
      Both L-canavanine and L-canaline were cytotoxic to peripheral blood
      mononucleocytes (PBMCs) in culture. Additionally, the mononucleocytes were
      concurrently exposed to either L-canavanine or L-canaline and each one of a
      series of compounds that may act as metabolic inhibitors of the action of L
      canavanine and L-canaline (L-arginine, L-ornithine, D-arginine, L-lysine, L
      homoarginine, putrescine, L-omega-nitro arginine methyl ester and L-citrulline).
      The capacity of these compounds to overcome the cytotoxic effects of L-canavanine
      or L-canaline was assessed in order to provide insight into the biochemical
      mechanisms that may underlie the toxicity of these two novel anticancer agents.
      The results of these studies suggest that the mechanism of L-canavanine toxicity
      is mediated through L-arginine-utilizing mechanisms and that the L-canavanine
      metabolite, L-canaline, is toxic to human PBMCs by disrupting polyamine
      biosynthesis. The elucidation of the biochemical mechanisms associated with the
      effects of L-canavanine and L-canaline on lymphoproliferation may be useful for
      maximizing the therapeutic effectiveness and minimizing the toxicity of these
      novel anticancer agents.

PMID- 11984076
TI  - Modification of adriamycin pharmacokinetics by direct electric current in rats.
AB  - Adriamycin (ADR, doxorubicin), a drug having cardiotoxicity, is electrically
      charged as a cation in blood. We therefore investigated whether iontophoresis
      caused by direct electric current (DC; 50 microA, 90 min) would cause systemic
      modification of ADR pharmacokinetics. Cathode and anode were placed into a right
      kidney and muscles of the abdominal wall, respectively, in six Donryu rats.
      Urinary excretion of ADR, as measured by catheterizing into the right kidney, was
      significantly higher in the DC group than in the controls (p < 0.05). Both
      plasmic and renal ADR clearances were significantly higher in the DC group
      (p<0.005 and p<0.001, respectively). Tissue ADR concentrations were significantly
      lower in the DC group (heart: p<0.003; liver and lung: both p<0.05). These
      results suggest that electric therapy might potentially induce modification of
      ADR pharmacokinetics by iontophoresis, and that the therapy might effectively
      change ADR concentration both locally and systemically.

PMID- 11984077
TI  - Life-threatening anaphylactoid reaction to amifostine used with concurrent
      chemoradiotherapy for nasopharyngeal cancer in a patient with dermatomyositis: a
      case report with literature review.
AB  - Dermatomyositis is associated with malignancy in approximately 20-25% of cases.
      The most common associated cancers are ovarian, lung, pancreatic, stomach, colon
      and non-Hodgkin's lymphoma. Nasopharyngeal cancer is not common in the Caucasian
      population; however, there is a much higher incidence in Asian patients.
      Radiotherapy is the mainstay of treatment for early nasopharyngeal cancer, but
      combination chemoradiotherapy is becoming more common for patients with advanced
      disease since the Intergroup trial 0099 demonstrated improved progression-free
      survival and overall survival for chemoradiotherapy. Increasingly, the cytotoxic
      agent amifostine is being used prior to radiotherapy in an attempt to decrease
      associated morbidities. Amifostine has been found to significantly decrease acute
      and chronic xerostomia but not mucositis. It appears to be selectively protective
      to salivary glands and kidneys without being tumor protective. The most common
      side effects associated with amifostine are nausea, vomiting, hypotension,
      hypocalcemia and allergic reactions. We describe the case of a man with
      dermatomyositis and stage IV nasopharyngeal cancer treated with chemoradiotherapy
      and s.c. amifostine. The patient suffered a life-threatening anaphylactoid
      reaction to amifostine.

PMID- 11984078
TI  - Isothiocyanates: mechanism of cancer chemopreventive action.
AB  - Dietary and synthetic isothiocyanates have cancer chemopreventive activity.
      Dietary isothiocyanates are formed from glucosinolate precursors of ingested
      green vegetables. Isothiocyanates are absorbed across intestinal cell membranes
      by passive diffusion and bind reversibly to plasma protein thiols by
      thiocarbamoylation. Free isothiocyanate enters cells and is converted to the
      glutathione conjugate by glutathione S-transferases (GSTs). The glutathione
      conjugate is exported from cells by multidrug resistance proteins (MRPs), and
      metabolized in the mercapturic acid pathway to the corresponding mercapturic
      acid. The isothiocyanate is reformed by fragmentation of mercapturic acid pathway
      metabolites; it is inactivated by slow hydrolysis to the corresponding amine that
      is inactive in chemoprevention. Depletion of cellular glutathione and protein
      thiocarbamoylation activates signal transduction for cancer chemoprevention.
      Isothiocyanates inhibited and inactivated cytochrome P450 isoforms. They induced
      increased expression of GST, NADPH: quinone oxidoreductase, aldo-keto reductase
      and gamma-glutamylcysteine synthetase. These responses were coordinated at the
      transcription level by nuclear factor-erythroid 2 p45-related factor-2 acting
      through the antioxidant/electrophile enhancer response element and stimulated by
      the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase
      kinase-1 and c-Jun N-terminal kinase-1 (JNK1) pathway. Isothiocyanates also
      induced apoptosis of pre-cancerous cells and tumor cells activated by caspase-8
      and potentiated by JNK1. The chemopreventive activity of isothiocyanates is
      influenced by the isothiocyanate bioavailability-as is toxicity, GST
      polymorphism, protein thiocarbamoylation and probably also by MRP expression.
      These features of isothiocyanate metabolism and chemoprevention deserve further
      investigation.

PMID- 11984079
TI  - Treatment of myeloma: recent developments.
AB  - Melphalan was the first described treatment for patients with multiple myeloma in
      the 1960s and is still being used in clinical practice. However, the use of
      melphalan in combination with prednisone resulted in a median survival of only 2
      3 years. Therefore, the dose of melphalan has been intensified since then (140
      200 mg/m(2)). In order to diminish treatment-related morbidity and mortality due
      to severe myelosuppression induced by these regimens, high-dose melphalan is
      currently supported with autologous stem cells. Indications for high-dose therapy
      and the role of further intensification by performing second or allogeneic
      transplantations are discussed. Furthermore, new therapeutic modalities, such as
      inhibitors of angiogenesis, also showing direct antiproliferative, cytokine
      related and immunomodulatory effects on plasma cells (thalidomide and its newer
      derivatives), inhibitors of the transcription factor NF-kappa B (proteasome
      inhibitors) and immunotherapy are described.

PMID- 11984080
TI  - Tumor-specific DNA in plasma of breast cancer patients.
AB  - The presence of DNA fragments circulating in cancer patients was described a
      number of years ago. The mere presence of DNA in the circulation is not
      indicative of cancer. However, there are reports that apoptosis and necrosis of
      the cancer cells can increase the levels of circulating DNA. The study of plasma
      DNA with the detection of genetic abnormalities associated with specific cancers
      has produced some promising results. Primary cancer often harbors ras or p53
      mutations and the detection of these mutations in free circulating DNA could
      indicate the presence of cancer. Other approaches have included detection of
      specific losses of heterozygosity (LOH), microsatellite instability (MI) and
      promoter hyper-methylation. For breast cancer, studies published to date have
      focused on detecting LOH, MI and methylation of the p16INK4A promoter. Good
      concordance between alterations in the primary tumor and detection of the same
      alterations in the circulation has been observed. Also, it is encouraging to note
      that DNA alterations have been detected in patients with small or even in situ
      lesions, indicating that circulating tumor DNA is shed early in the disease
      process. If 'universal' breast-specific DNA alterations can be identified, this
      approach may hold significant promise for early detection of breast cancer.

PMID- 11984081
TI  - Identification of phenyl-pyridine-2-carboxylic acid derivatives as novel cell
      cycle inhibitors with increased selectivity for cancer cells.
AB  - Ro 41-4439, a phenyl-pyridine-2-carboxylic acid derivative, was identified by a
      cell-based screening approach that exploits the differences between normal and
      cancer cells in their sensitivity to cytotoxic agents. This compound showed low
      micromolar antiproliferative activity and cytotoxicity against a broad panel of
      human cancer cell lines in vitro, and over 10-fold selectivity to cancer cells
      when tested in parallel with a panel of proliferating normal human cells.
      Cytotoxicity of Ro 41-4439 is due to arrest of cell cycle progression in mitosis
      followed by induction of apoptosis. Four-week treatment of nude mice bearing
      established mammary tumor xenografts (MDA-MB-435) with well-tolerated doses of
      the compound showed 73% inhibition of tumor growth. Limited exploration of
      structure-activity relationships involving side chain length, and aryl and
      pyridine rings allowed for the identification of more potent analogs.

PMID- 11984082
TI  - Synthesis and cytogenetic effects of aminoquinone derivatives with a di- and a
      tripeptide.
AB  - Quinones are of significant interest due to their important role in specific
      cellular functions. Quinoproteins are a big class of oxyreductive agents
      occurring in bacteria and other organisms. In this investigation derivatives of 2
      amino-1,4-benzoquinone, 2-amino-1,4-naphthoquinone and 2-amino-5,8-dihydroxy-1,4
      naphthoquinone with a di- and a tripeptide were prepared for first time. The
      effect of the synthesized compounds on sister chomatid exchange (SCE) rates and
      human lymphocyte proliferation kinetics on a molar basis was studied. Among these
      coupled products the most effective in inducing SCEs and depressing proliferation
      rate indices is the coupling product of 2-amino-1,4-naphthoquinone with the
      tripeptide GHK (10). Next in order of magnitude in inducing cytogenetic effects
      is 2-amino-1,4-naphthoquinone (2) and its coupling products with glycine and
      serine (4 and 5), while the rest displayed marginal activity.

PMID- 11984083
TI  - Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by
      mistletoe extracts in vitro.
AB  - Extracts of Viscum album (mistletoe) are widely used as complementary cancer
      therapies in Europe. The mistletoe lectins have been identified as the main
      active principle of mistletoe extracts. They have been shown to exhibit cytotoxic
      effects as well as immunomodulatory activities. The latter is exemplified by
      induction of cytokine secretion and increased activity of natural killer cells.
      Recent reports, however, indicated possible tumor growth stimulation by mistletoe
      extracts. Therefore, the three aqueous mistletoe extracts (Iscador M special,
      Iscador Qu special and Iscador P) were evaluated for antiproliferative and/or
      stimulatory effects in a panel of 16 human tumor cell lines in vitro using a
      cellular proliferation assay. The results show no evidence of stimulation of
      tumor growth by any of the three Iscador preparations, comprising central nervous
      system, gastric, non-small cell lung, mammary, prostate, renal and uterine cancer
      cell lines, as well as cell lines from hematological malignancies and melanomas.
      On the contrary, Iscador preparations containing a high lectin concentration
      (Iscador M special and Iscador Qu special) showed antitumor activity in the
      mammary cancer cell line MAXF 401NL at the 15 microg/ml dose level with a more
      than 70% growth inhibition compared to untreated control cells. In addition, a
      slight antitumor activity (growth inhibition 30-70%) was found in three tumor
      cell lines for Iscador M special and in seven tumor cell lines for Iscador Qu
      special, respectively. Iscador P, which contains no mistletoe lectin I, showed no
      antiproliferative activity.

PMID- 11984084
TI  - Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin
      743 administered as a 1- and 3-h infusion in a phase I study.
AB  - Ecteinascidin 743 (ET-743) is an anticancer agent derived from the Caribbean
      tunicate Ecteinascidia turbinata. In the present article, the pharmacokinetics
      and pharmacodynamics of ET-743 are described within a phase I study. Forty
      patients with solid tumors initially received ET-743 as a 1-h i.v. infusion every
      21 days at nine dose levels (50-1100 microg/m(2)). The maximal tolerated dose
      (MTD) was 1100 microg/m(2), with thrombocytopenia and fatigue as dose-limiting
      toxicities (DLTs). As this MTD was substantially lower than in parallel phase I
      studies, dose escalation continued using a prolonged, 3-h infusion. Thirty-two
      patients were entered at five dose levels (1000-1800 microg/m(2)). The MTD was
      1800 microg/m(2) with pancytopenia and fatigue as DLTs. The recommended phase II
      dose was 1650 microg/m(2) given over 3 h at which 12 patients were treated.
      Pharmacokinetic monitoring was performed for both treatment schedules. Non
      compartmental pharmacokinetic parameters at the recommended dose with the 3-h
      infusion were (mean value+/-SD): clearance 87+/-30 l/h and mean elimination half
      life 26+/-7 h. Pharmacokinetics were linear at the dose range tested with this
      schedule. The percentage decrease in platelets, white blood cells and neutrophils
      correlated with the area under the plasma concentration versus time curve (AUC),
      dose and maximal plasma concentration (C(max)). Hepatic toxicity increased with
      dose, AUC and C(max). Administration of 1650 microg/m(2) ET-743 over 3 h seemed
      clinically feasible; pharmacokinetics were linear with this schedule. Hepatic and
      hematological toxicities correlated with exposure to ET-743.

PMID- 11984085
TI  - Influence of amifostine on toxicity of CHOP in elderly patients with aggressive
      non-Hodgkin's lymphoma--a phase II study.
AB  - Due to concerns about toxicity, many elderly patients with aggressive non
      Hodgkin's lymphoma (NHL) are not considered candidates for standard chemotherapy
      with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The
      cytoprotective agent amifostine has the potential to reduce toxicity when added
      to chemotherapy. The purpose of the current study was to examine the toxicity of
      CHOP combined with amifostine in elderly patients with aggressive NHL. A
      prospective phase II study was performed in patients aged 60 years and older.
      Patients with stage I/II disease received 4 cycles of CHOP followed by involved
      field irradiation. Patients with stage III/IV received 6-8 cycles of CHOP.
      Amifostine (740 mg/m(2)) was administered as a 15-min i.v. infusion immediately
      before chemotherapy. Forty-one (median age 69.5 years, range 60-87) of 49
      consecutive previously untreated patients, aged 60 years and older, with
      aggressive NHL seen in our center were included in the study. Twenty-one patients
      had stage I/II disease and 20 had stage III/IV disease. The patients received a
      total of 207 cycles of amifostine-CHOP. Infusion of amifostine caused mild to
      moderate transient side effects, including a drop of systolic blood pressure >20
      mmHg in 54 cycles and nausea/vomiting in 36 cycles. Hematotoxicity of CHOP
      consisted of leukopenia grade 4 in only 15.4% of cycles. There were two cases of
      grade 3 anemia. No thrombocytopenia higher than grade 2 occurred. Febrile
      neutropenia was rare, occurring in 4.3% of cycles. One patient died after the
      first CHOP administration because of anthracycline-related acute cardiomyopathy
      (corresponding to a toxic death rate of 2.4%). The complete response rates were
      85 and 75% in stage I/II and stage III/IV patients, respectively. After median
      follow-up of 33 months (range 17-50 months) the median overall survival was not
      reached in patients with stage I/II and was found to be 32 months in patients
      with stage III/IV. At 2 years, 76% of patients with stage I/II and 70% with stage
      III/IV were alive. Twelve of the 15 patients who died were aged older than 70.
      Amifostine pre-treatment was associated with a low toxicity of CHOP in elderly
      patients with aggressive NHL treated with curative intent. Treatment outcomes
      appeared not to be impaired by the addition of amifostine to CHOP. This schedule
      merits further testing in a randomized trial.

PMID- 11984086
TI  - Capecitabine in patients with breast cancer relapsing after high-dose
      chemotherapy plus autologous peripheral stem cell transplantation--a phase II
      study.
AB  - Capecitabine, a tumor-selective, oral fluoropyrimidine, has demonstrated
      significant antitumor activity in patients with metastatic breast cancer. In this
      open-label monocenter phase II study the efficacy and safety of capecitabine in
      patients with metastatic breast cancer who relapsed after high-dose chemotherapy
      was examined. Female patients 18-65 years of age, with a histologically confirmed
      diagnosis of metastatic breast cancer, who relapsed after high-dose chemotherapy
      (adjuvant and/or metastatic) followed by autologous peripheral blood stem cell
      transplantation (PBSCT) and who had been treated in their course of the disease
      with an anthracycline and/or an anthracycline/taxane containing regimen were
      included into this clinical study. Capecitabine was applied as the first salvage
      chemotherapy at relapse after high-dose chemotherapy (1250 mg/m(2) b.i.d. p.o.
      for 14 days followed by 7 days rest period). Responding patients or those with
      stable disease after two treatment cycles were offered to continue treatment
      until tumor progression. Response rate, time to disease progression, survival,
      toxicity and quality of life were assessed. Fourteen patients between 35 and 60
      years (median 45.5 years) entered this study and received a median number of 5
      cycles (range 1-19) of capecitabine. All patients were evaluable for response.
      All patients had been pretreated with 1-2 cycles of high-dose chemotherapy plus
      PBSCT. Furthermore, 13 patients had additionally received local radiotherapy. On
      average, the patients showed metastatic disease in two organ sites (range 1-4
      sites). One patient obtained a complete response and five patients a partial
      response, accounting for a response rate of 42.9% [95% confidence interval
      (17.7%; 71.1%)]. All responses were already achieved at the first observation
      time point 6 weeks after treatment initiation. Two further patients obtained
      stable disease for at least 12 weeks. At the time of final analysis all patients
      have progressed. Median time to progression was 2.8 months (range 0.4-13.3
      months). No median survival time was reached (range 3.9-36.5 months, at the time
      of reporting eight patients were alive and six patients had died). Two patients
      developed grade III granulocytopenia. Five patients developed grade III hand-foot
      syndrome. One patient had the combination of nausea, fever and diarrhea grade
      III. All adverse events were considered manageable. We conclude that capecitabine
      as single-agent oral chemotherapy is active and well tolerated in heavily
      pretreated patients with breast cancer. It can be safely used in patients who
      have been intensively pretreated by myelotoxic chemotherapy or who have even
      relapsed after high-dose chemotherapy with PBSCT.

PMID- 11984087
TI  - Dihydropyrimidine dehydrogenase-related enzymes predict efficacy and adverse
      reactions of UFT1+cisplatin neoadjuvant chemotherapy for gastric cancer.
AB  - Dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHP) are metabolic
      enzymes of fluoropyrimidine. UFT containing uracil (U) and Tegafur is the first
      reported DPD-inhibitory fluoropyrimidine. To clarify the significance of the
      enzyme activities, we examined the relationships between the effects and adverse
      reactions, and DPD and DHP activities in gastric cancer treated with
      UFT1+cisplatin neoadjuvant chemotherapy. Twenty-five gastric cancer patients were
      administered UFT at 370 mg/m(2)/day for 21 days and cisplatin at 15 mg/m(2)/day
      for 2 days. Dihydrouracil (DU) and U levels in the urine and DPD activities in
      the resected tumors were measured. Chemotherapeutic effects were classified
      histologically into non-responder and responder groups. The responder group
      accounted for 48% of the patients. All six patients with high DPD activities (>
      or = 0.08 nmol/min/ww) belonged to the non-responder group and 11 of 19 patients
      with low DPD activities (<0.08 nmol/min/ww) belonged to the responder group; the
      difference was significant (p=0.0435). Adverse reactions to UFT occurred in four
      patients, all of whom were among the six patients with abnormal DU/U values. The
      incidence of UFT adverse reactions was estimated at 67%. In conclusion, the
      measured levels of DPD-related enzyme activities appear to be significant for
      predicting the effects and adverse reactions to chemotherapy.

PMID- 11984088
TI  - Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast
      cancer: a phase II pilot study.
AB  - The aim of the present trial was to investigate the protective effects on ovarian
      function, and the efficacy and tolerability of goserelin added to adjuvant
      chemotherapy for early breast cancer. Following surgical treatment, 64
      premenopausal patients with early breast cancer received goserelin 3.6 mg (every
      28 days for 1 year) and an adjuvant treatment which was chosen according to the
      patient's prognosis. Median age was 42 years (range 27-50). ECOG performance
      status was 0-1 in all patients. Twenty-eight patients (44%) had estrogen receptor
      (ER)+ tumors and 36 (56%) patients had ER- tumors. Fifty-two (81%) patients had
      stage II disease and 12 (19%) had stage III disease. Eighteen patients received
      cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, 46 patients
      received an anthracycline-based regimen, and nine of them received high-dose
      chemotherapy and autologous peripheral blood progenitor cell transplantation.
      Fifty-one patients (80%) were irradiated. ER+ patients also received tamoxifen
      for 5 years. Serum estradiol was suppressed to values below 40 pg/ml in all
      patients. After a median follow-up of 55 months, 86% of patients had resumed
      normal menses, 84% of patients were disease-free and 94% were alive. The 1-, 3-
      and 5-year projected recurrence-free survival rates were 100, 81 and 75%,
      respectively. Five years after treatment one patient had a pregnancy that ended
      with a normal childbirth. No unexpected adverse events were reported. These data
      show that the addition of goserelin to adjuvant therapy of premenopausal patients
      with early breast cancer is well tolerated and protects long-term ovarian
      function.

PMID- 11984089
TI  - Docetaxel does not impair cardiac autonomic function in breast cancer patients
      previously treated with anthracyclines.
AB  - The effects of docetaxel treatment on autonomic cardiac function was studied with
      24-h ECG recordings in breast cancer patients pretreated with anthracyclines.
      Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses
      of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate
      variability (HRV) in both the time and frequency domain were assessed from 24-h
      ECG recordings. The acute effects of docetaxel were calculated from 1-h
      recordings immediately prior to, during and after infusion. Long-term effects
      were evaluated from 24-h recordings performed before treatment and after 3-4
      courses of docetaxel. There was no increase in the number of cardiac
      extrasystoles during docetaxel infusion. The number of ventricular extrasystoles
      decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion
      (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4
      courses of docetaxel. The treatment did not abolish circadian variability of the
      heart rate. Docetaxel did not deteriorate autonomic cardiac function. In
      conclusion, our findings suggest that docetaxel does not have harmful cumulative
      effects on autonomic control of the heart and is therefore unlikely to be
      cardiotoxic.

PMID- 11984090
TI  - Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is
      an effective therapy in advanced gastric cancer.
AB  - Treatment failure of surgically treated gastric cancer is attributed to the
      spread of gastric cancer cells into the abdominal cavity and lymphatic or
      hematogenic canals. In the present study, local injection of mitomycin C bound to
      activated carbon (M-CH) combined with i.p. hyperthermic hypo-osmolar infusion
      (IPHHOI) was intraoperatively administered to prevent lymph node recurrence and
      peritoneal recurrence of gastric cancer. Between April 1998 and August 1999, 79
      patients with advanced gastric cancer were allocated randomly to two groups.
      Forty patients underwent M-CH plus IPHHOI combined with surgery (M-CH1+IPHHOI
      group) and the remaining 39 underwent surgery alone (control group). Lymph node
      and peritoneal recurrence were significantly decreased in the M-CH1+IPHHOI group
      compared to that in the control group (p<0.05). The 1- and 2-year survival rates
      for the M-CH1+IPHHOI group were 91.2 and 72.1%, and those for the control group
      were 78.9 and 45.5%. The M-CH1IPHHOI group reaped a significant survival benefit
      (p=0.0352) compared to the control group. Although this study was conducted
      randomly for a small number of patients and short time, compared with the control
      group, the M-CH1+IPHHOI group had a beneficial effect in preventing lymph node
      recurrence and peritoneal recurrence after curative gastrectomy for advanced
      gastric cancer.

PMID- 11984092
TI  - Presenter-to-Go for the Handspring.

PMID- 11984091
TI  - Using Web technology in graduate and undergraduate nursing education.

PMID- 11984093
TI  - Nursing Informatics: Education for Practice.

PMID- 11984094
TI  - Ethical issues of informed consent: mothers' experiences enrolling their children
      in bone marrow transplantation research.
AB  - Twelve mothers whose children had undergone bone marrow transplantation were
      interviewed about their experiences giving informed consent. They were asked to
      describe how they were introduced to bone marrow transplantation as a course of
      action to treat their gravely ill children, what their understanding of the
      protocol was, and the process by which they gave their consent. Their stories
      reveal complex ethical issues that may surface in the course of informed consent
      for research involving children. Findings suggest that mothers perceive life-and
      death circumstances when a child is offered bone marrow transplantation, altering
      the voluntary nature of the research enterprise. The emotional trauma of the
      diagnosis decreases a mother's ability to absorb and understand vital
      information, and the emergent nature of the children's condition and the urgency
      to begin treatment further compromise informed consent by constricting the time
      and resources mothers may need to make a decision. Once a protocol is underway,
      mothers often experience regrets and self-recriminations about their decision to
      consent. Recommendations are offered that expand upon the current
      cognitive/rational approach to informed consent and take into account emotional
      experiences and the importance of building relationships to ensure informed
      consent over the life of a clinical trial.

PMID- 11984095
TI  - Determinants of exercise intention and behavior in survivors of breast and
      prostate cancer: an application of the theory of planned behavior.
AB  - The purpose of this study was to evaluate the theory of planned behavior as a
      framework for understanding exercise intention and behavior in survivors of
      breast and prostate cancer. Participants were 83 survivors of breast and 46
      survivors of prostate cancer who were diagnosed within the previous 4 years and
      had completed treatment. Each participant completed a mailed self-administered
      questionnaire that assessed exercise during the previous week, demographic and
      medical variables, and the theory of planned behavior. For survivors of breast
      cancer, regression analyses indicated that attitude, subjective norm, and
      perceived behavioral control explained 45% of the variance in exercise intention
      with attitude, subjective norm, and perceived behavioral control each uniquely
      contributing to intention. Furthermore, exercise intention explained 30% of the
      variance in exercise behavior; however, perceived behavioral control added no
      unique variance. For survivors of prostate cancer, attitudes, subjective norm,
      and perceived behavioral control explained 36% of the variance in exercise
      intention, but only perceived behavioral control made a significant unique
      contribution. Furthermore, intention explained 36% of the variance in exercise
      behavior; however, perceived behavioral control added no unique variance. Results
      suggest that nurses may use the theory of planned behavior as a model for
      understanding the determinants of exercise intentions and behavior in survivors
      of breast and prostate cancer.

PMID- 11984096
TI  - The face of suffering among women with breast cancer-being in a field of forces.
AB  - Through qualitative interviews, the suffering experiences of women with breast
      cancer and their significant others were disclosed. Seventeen women with
      different stages of breast cancer and 16 significant others from 4 different care
      cultures in Sweden and Finland participated. Five of the women had advanced
      metastatic breast cancer, and 12 had a localized disease. Mean age was 48 years.
      As a methodology, a team approach, inspired by the Vancouver School of Doing
      Phenomenology, was used. The findings elucidate how the suffering experience
      touched the women's inner existence and values. This can metaphorically be
      described as a "field of force" and affected everything in the women's lives,
      including their views of themselves and their relationships. Existential
      questions were raised about life and death and the meaning of life. In their
      suffering, the women's dependency upon significant others, as well as healthcare
      personnel, was prominent. Suffering related to healthcare was a strong theme.
      Different faces of suffering related to breast cancer may still be unknown by
      healthcare professionals working in cancer care.

PMID- 11984098
TI  - A pilot study of magnetic therapy for hot flashes after breast cancer.
AB  - The purpose of this randomized placebo-controlled crossover pilot study was to
      evaluate the effectiveness and acceptability of magnetic therapy for hot flashes
      among breast cancer survivors. Participants completed a 24-hour baseline hot
      flash monitoring session, wore the magnetic devices or placebo for 3 days,
      completed an after-treatment hot-flash monitoring session, experienced a 10-day
      washout period, and then crossed over to the opposite study arm. Magnetic devices
      and placebos were placed on 6 acupressure sites corresponding to hot-flash
      relief. Complete data were available from 11 survivors of breast cancer. Results
      indicated magnetic therapy was no more effective than placebo in decreasing hot
      flash severity, and contrary to expectations, placebo was significantly more
      effective than magnets in decreasing hot-flash frequency, bother, interference
      with daily activities, and overall quality of life. Implications for clinical
      practice and future research include the need to explore alternative
      interventions aimed at alleviating hot flashes in this population.

PMID- 11984099
TI  - Applications of advances in molecular biology and genomics to clinical cancer
      care.
AB  - Genetics technologies, methods, and discoveries are being integrated rapidly into
      medical and nursing practices in a variety of ways. The purpose of this article
      is to familiarize nurses with how new genetic technologies and discoveries are
      being incorporated into various phases of clinical oncology practice. The scope
      of this article is broad to provide an overview of the of ways in which cancer
      prevention, surveillance, diagnosis, prognosis, monitoring, treatment, and gene
      therapy are evolving due to advances in the molecular biology of cancer. We use
      specific examples to demonstrate the use of genetic information to achieve these
      objectives and to illustrate principles and strategies that may be applied to a
      variety of cancers.

PMID- 11984100
TI  - Pain management autobiographies and reluctance to use opioids for cancer pain
      management.
AB  - Although pain management education results in improved pain control for some
      patients, it does not work for all patients because some patients remain
      reluctant or unwilling to use prescribed analgesics to their optimal effect. In a
      randomized clinical trial that tested the effectiveness of the PRO-SELF Pain
      Control Program, 11 patients declined to increase their analgesic use despite
      moderate to severe pain. These patients were selected for a qualitative analysis
      of their audiotaped discussions about pain management with their intervention
      nurses. This analysis revealed that these patients often spontaneously provided
      detailed explanations about why they were reluctant or unwilling to take
      analgesics in general or opioids in particular. We termed these explanatory
      accounts pain management autobiographies because of their narrative character and
      multilayered, richly detailed quality. Pain management autobiographies included
      stories about (1) previous experience with chronic pain management, including
      stigmatizing interactions with clinicians and family members; (2) bad experiences
      with cancer pain management, including severe constipation; and 3) strongly held
      conventions about medication use, including the belief that all medications are
      "toxins" that should be avoided. The study findings suggest that a small subset
      of patients with cancer pain may need interventions such as individual or family
      counseling or alternative pain management strategies to augment education about
      opioids.

PMID- 11984101
TI  - The Chinese translation of the Index of Nausea, Vomiting, and Retching.
AB  - The purpose of this study was to determine reliability and validity of the
      Chinese version of the Index of Nausea, Vomiting, and Retching (INVR) and the
      Index of Nausea and Vomiting Form 2 (INV-2) to provide a reliable and valid
      measure of nausea, vomiting, and retching for Chinese nurses and other healthcare
      providers. An integrative translation method was used in the study. The
      reliability and validity of the Chinese versions of the INVR and the INV-2 was
      evaluated using test-retest, parallel forms, and crossover design. A convenience
      sample of 177 Chinese-speaking participants was accrued from a large teaching
      cancer institute and a teaching obstetric hospital in Beijing, Peoples Republic
      of China. The integrative translation method was proven to be an effective method
      for translating instruments from the source to the target language. The Chinese
      versions of both the INV-2 and INVR were found to have high Cronbach's alpha
      scores and high agreement rates. The responses to the Chinese version of INVR
      were more frequently consistent than the responses to the INV-2. The majority of
      the patients voiced preference for the INVR. The findings suggest the
      significance of the Chinese versions of INVR and INV-2 in terms of nursing
      practice. The findings also support the cross-cultural method for future study at
      international level.

PMID- 11984102
TI  - Attempting to find meaning in illness to achieve emotional coherence: the
      experiences of patients with colorectal cancer.
AB  - The aim of the study was to explore the emotional and interactional perspectives
      of the meaning of illness in patients with colorectal cancer. Fifty-two
      respondents were included in the study. Data were obtained through an open-ended
      question at the time of diagnosis as well as 3 and 12 months after diagnosis. The
      constant comparative method of data analysis, consisting of an interpretation of
      the data, was used. The overall ascribed meaning was expressed in the main theme,
      attempting to find meaning in illness to achieve emotional coherence. The main
      theme consisted of 2 dimensions: unified and dichotomized embodiment. The unified
      embodiment dimension subthemes include gratefulness, confidence in oneself and
      others, and looking forward to creating a new future. The dichotomized embodiment
      dimension subthemes include altered self-value, loss of temporality, and
      infringement of body integrity. The characteristics of unified embodiment were
      hope and faith, a strong self-value, and an anticipated future. For dichotomized
      embodiment, the characteristics were the struggle, loss of temporality,
      nonmovement, and lack of hope and faith. The study provided a theoretical basis
      that is relevant for both nursing practice and nursing education.

PMID- 11984103
TI  - Interest and participation in support group programs among patients with
      colorectal cancer.
AB  - Previous studies have demonstrated that support intervention improved quality of
      life and survival for patients with breast, melanoma, prostate, and
      gastrointestinal cancer. A standardized approach to encourage participation in
      support group programs among patients with colorectal cancer (CRC) had been
      initiated at this study site. The purpose of this study was to examine the
      characteristics of patients with CRC interested in this type of intervention and
      to identify barriers to attendance at an established patient support program.
      Consecutive patients with CRC were informed and encouraged to attend Wellspring,
      a nonprofit patient support program that offers a wide range of services. A
      patient survey was conducted and correlated with data on the clinical, social,
      and demographic characteristics of patients. Factors predictive of interest in
      the Wellspring support program and barriers to attendance were examined.Fifty
      eight patients were eligible for this study. A total of 44 (76%) surveys were
      completed. Predictors of interest in patient support were age less than 65 years,
      encouragement from medical staff to attend, level of education, comfort in
      spiritual beliefs, religious affiliation, and complementary/alternative medicine
      use. Disease stage, gender, ethnicity, and level of social supports were not
      significant in this population. Although patients were routinely informed about
      the program in a standardized fashion, a significant proportion (36.4%) of
      patients did not recall receiving encouragement. Multiple logistic regression
      showed that level of education and recollection of encouragement from medical
      staff were independent predictors of interest. Although 14 patients were
      interested in attending (32%), only 4 ultimately attended Wellspring programs
      (9.1%). The most frequently cited barrier to attendance was a perception of
      adequate support at home, followed by living too far away, no perceived need of
      supports, and not feeling well.A significant proportion of patients with CRC are
      interested in structured support programs, but only a minority of patients
      ultimately participate in such programs. Further participation may be achieved by
      recognizing common barriers to participation and optimizing strategies to enhance
      attendance. Optimizing use of support services such as Wellspring has the
      potential to improve the effectiveness of the multidisciplinary cancer care of
      patients with CRC.

PMID- 11984104
TI  - Influencing factors of place of death among home care patients with cancer in
      Taiwan.
AB  - Multiple factors, including personal and cultural values, physical and medical
      factors, and various healthcare systems' forces, influence the place of death of
      patients with cancer. The purpose of this retrospective chart audit study was to
      examine the influence of sociodemographic factors, family support, patient
      functioning, and care needs on the place of death for patients with cancer served
      by a home care program in Taiwan. Among the 264 study patients, 182 (69%) died at
      home and 82 (31%) died in the hospital. Significant differences were found
      between patients dying at home or in a hospital predominantly in the categories
      of patient functioning and care needs. From the multivariate logistic regression
      model, home care patients with cancer who were never rehospitalized, who received
      more home care visits, and who were referred to home care services at the
      greatest functionally dependent status and with pain were more likely to die at
      home. Overall, this model could accurately classify 78% of the place of death,
      which is higher than other published studies. Understanding factors that
      influence place of death of terminally ill patients with cancer allow healthcare
      professionals to modify healthcare systems and tailor effective interventions to
      help patients die at the place they prefer.

PMID- 11984106
TI  - What makes advanced practice nurses special?

PMID- 11984107
TI  - The emerging role of advanced nursing practice in acute pain management
      throughout Canada.
AB  - The purpose of this study was to describe the role qualifications and
      responsibilities related to advanced nursing practice in acute pain management
      across Canada. The Canadian Nurses Association national framework on advanced
      nursing practice was used as a guide to identify role components for nurses
      within this specialty. A self-administered questionnaire of fixed choice and open
      ended questions was mailed to nurses in acute pain management throughout Canada.
      Respondents identified their primary role responsibilities as clinical,
      educational, and administrative. Role challenges included lack of
      administrative/colleague support, complexity of pain problems, role definition,
      and acceptance. Key areas of positive outcomes involved the patient as well as
      interdisciplinary and nursing teams. Nurses described the ability to provide
      continuity of care, patient and staff education, and leadership in pain
      management as important and rewarding. The role of advanced nursing practice in
      acute pain management throughout Canada is evolving. The affect of this role
      promises to enhance the quality of pain management for healthcare professionals
      and their patients.

PMID- 11984108
TI  - Dealing with the knowledge explosion.

PMID- 11984109
TI  - The clinical leadership role of the CNS in the identification of nursing
      sensitive and multidisciplinary quality indicator sets.
AB  - Within a team-oriented approach to healthcare, the demonstration of quality is
      challenging. Multidisciplinary quality indicators ideally represent all pertinent
      stakeholders and are preferred when evaluating the quality of care for specific
      patient populations. Recently, however, nursing-sensitive indicators have been
      developed that reflect the unique contribution of nursing to patient outcomes.
      Because nursing-sensitive quality indicators reflect nursings' accountability for
      patient care, they must also be considered when identifying indicators sets.
      Controversy exists concerning the appropriate definition, number, and approach to
      indicator identification. Many organizations are attempting to measure everything
      to ensure that all appropriate indicators are represented. To incorporate both
      nursing-sensitive and multidisciplinary quality indicators, a phased organization
      wide approach is advocated. Through clinical leadership skills combined with the
      advanced practice roles of consultant, educator, and researcher, the clinical
      nurse specialist can facilitate the inclusion of relevant indicators, preserve
      both multidisciplinary and nursing-sensitive approaches, and maintain efficiency
      during the process. The clinical nurse specialist, with clinical expertise and
      advanced education has a unique leadership role in the identification of the
      resultant critical indicator matrix.

PMID- 11984110
TI  - Searching for information for presentations and publications.
AB  - Numerous information sources are available to the clinical nurse specialist
      preparing a presentation or writing a manuscript for publication. However,
      searching through this information to identify reputable sources and reliable
      data can be time consuming. Using a search plan that incorporates a timeline
      increases efficiency and helps visualize progress. A targeted search of
      biomedical databases, such as MEDLINE and PubMed, retrieves pertinent journal
      articles and avoids the "hit-and-miss" approach often used by novice speakers and
      authors. Information should be reviewed and organized soon after it is obtained
      so that more time can be spent writing and less time spent locating a specific
      reference or piece of information. The information can then be arranged in the
      order of the presentation or manuscript to facilitate the preparation process.

PMID- 11984111
TI  - Functions of the CNS in early discharge and home followup of very low birthweight
      infants. 1991.

PMID- 11984112
TI  - Hospital deaths and weekend admissions--how do we leap across a chasm?

PMID- 11984113
TI  - Continuous intravenous insulin infusion in patients with diabetes after cardiac
      surgery.

PMID- 11984115
TI  - Expectations about patient adherence.

PMID- 11984114
TI  - Keeping current with federal legislation affecting clinical nurse specialist
      practice.

PMID- 11984116
TI  - Patient outcomes beyond hospitalization: carotid endarterectomy surgical patient
      outcomes after a rapid recovery program.
AB  - Improved surgical techniques for carotid endarterectomy (CEA) surgical patients
      have resulted in improved postoperative hemodynamic stability of patients and
      reduced lengths of hospitalization. The purpose of this pilot project was to
      determine CEA patient outcomes after a rapid recovery hospitalization program.
      Thirty-nine patients were enrolled in the study and contacted at 1 month after
      CEA surgery to examine carotid occlusive disease clinical symptoms, functional
      status, atherosclerotic disease risk-factor reduction, and patient satisfaction.
      Findings of the pilot study demonstrated that CEA surgical patients were able to
      resume physical and psychosocial functioning by 1 month after surgery at levels
      comparable to preoperative functioning. Subjects reported relief of carotid
      artery occlusive disease symptoms and reported high levels of independent
      functioning and satisfaction with CEA surgery. Men in the study had significantly
      higher levels of reported independence in functioning compared with the women,
      using a "0" to "10" scale to rate level of functioning independence. Findings
      from the pilot study will be used to develop an early recovery and
      atherosclerotic disease risk-factor modification program for CEA surgical
      patients.

PMID- 11984122
TI  - Audio computerized self-report interview use in prenatal clinics: audio computer
      assisted self interview with touch screen to detect alcohol consumption in
      pregnant women: application of a new technology to an old problem.
AB  - Computer interviewing to obtain sensitive information is not a new concept.
      However, concerns about the acceptance of computers in disadvantaged populations
      with potentially low literacy led us to combine audio- and touch-screen
      technologies with an audio computerized self-report interview to obtain
      information about alcohol use. This study evaluated acceptance and ease of use by
      a disadvantaged population of pregnant women in the District of Columbia.
      Patients attending an initial visit at prenatal clinics answered questions
      anonymously about their consumption of alcoholic beverages and other personal
      information. The questionnaire was programmed on a laptop computer. The computer
      administered the recorded questions via earphones, as well as displayed them on
      the screen, and patients answered by touching the computer screen. Results were
      immediately available. A total of 507 women were interviewed, who were primarily
      African American, non-Hispanic, and never married. Nearly 24% did not complete a
      high school education, 43% were unemployed, and 30% received public assistance.
      Most of the women (59%) used computers occasionally (a few days a month) or
      never. Nearly all patients (96%) reported that the computer was not difficult to
      use, and approximately 90% liked answering the questions by computer. The study
      demonstrates that using computers to screen for alcohol use in disadvantaged
      pregnant populations is feasible and acceptable to the patients.

PMID- 11984123
TI  - A comparative analysis of computer-based grading programs.
AB  - There are several elements to nursing students' course grades: quizzes,
      examinations, and presentations. There are several weights for the elements,
      which adds to the complexity of calculating grades. The accuracy and efficiency
      of calculating grades can be increased with the help of an appropriate computer
      program. Nursing faculty may have access to a variety of these computer software
      programs to aid them in calculating and maintaining students' course grades.
      These programs include spreadsheets, specific grading programs, and grading
      features included in online course programs. This article reviews selected
      computer-based grading programs and reviewers' evaluation of each program, based
      on the major features.

PMID- 11984124
TI  - Measuring nurses' computer competency: an analysis of published instruments.
AB  - The rapid expansion of computer-driven technologies into multiple aspects of
      modern healthcare suggests that many of the important competencies of the 21st
      century nurse will encompass mastery of computer technology. This is a
      comprehensive review of the published measures of computer competence during the
      past 12 years. Essential knowledge, attitudes, and skills were identified and
      classified. Multiple competency assessment instruments of varying quality were
      examined. Little agreement was found regarding specific computer-focused
      competencies necessary for nurses. Taken as a whole, however, there is consensus
      that the computer-competent nurse possesses a general knowledge and understanding
      of computer technology, coupled with a positive attitude toward computers and
      software. In addition, such a nurse is skillful in computer hardware and software
      use and able to grasp how such technology benefits nursing and the overall
      healthcare environment.

PMID- 11984125
TI  - The potential contribution of social science to information technology
      implementation in healthcare.
AB  - Information technology systems in hospitals and other healthcare settings have
      sometimes proved difficult to implement successfully. Some of the problems
      encountered in the implementation of information technology systems in healthcare
      can be explained by the use of techniques and theoretical approaches derived from
      the social sciences, notably sociology and anthropology. Research from a variety
      of countries and healthcare systems confirms the explicative value of these
      techniques and approaches. These techniques can also be used to inform better the
      process of design and implementation of computer systems. Although they have been
      successfully applied in several industries and spread across several countries,
      these techniques have not yet been widely used in healthcare. This article
      suggests how these approaches can be fruitfully applied to the design and
      implementation of IT systems in healthcare and how this might be achieved.

PMID- 11984127
TI  - Progestogen-only contraceptives and cancer risk.

PMID- 11984128
TI  - A review of epidemiological studies on cancer in relation to the use of anti
      ulcer drugs.
AB  - H2-receptor antagonists have been widely used since the late 1970s for the
      treatment of gastrointestinal ulcers and other benign conditions of the stomach,
      oesophagus and duodenum. Several case reports suggested that long-term therapy
      with H2-receptor antagonists, mainly cimetidine and ranitidine, might increase
      the risk of gastric cancer. After early case reports, at least six analytical
      epidemiological studies (two cohort and four case-control) were published,
      including a total of about 1000 cases of gastric cancer. The relative risks (RR)
      were systematically and substantially elevated in the first year since starting
      H2-receptor antagonist use, and levelled off in the following years. Some excess
      risk was still apparent during the first 5 years of drug use, probably due to
      incorrect diagnosis and treatment of pre-existing neoplastic gastric lesions, but
      the estimated RR was not above unity for > or = 10 years since starting drug
      treatment in the two studies including information on long-term use. The findings
      of analytical epidemiological studies are thus consistent with the absence of a
      causal association between H2-receptor antagonist use and gastric cancer risk.
      Data on oesophageal and colorectal cancer do not support a relevant relation
      between cimetidine use and the risk of these neoplasms. With reference to total
      cancer mortality, in a Danish cohort study, for males the RR was 1.9 in the first
      year, and 1.4 in the first 5 years; corresponding values for females were 1.7 and
      1.5. In a British cohort study, the RR was 3.4 in the first year, and 1.3 in the
      years 2-10. The excess risk in the first year was essentially due to gastric
      cancer. Post-marketing surveillance data for omeprazole and other proton pump
      inhibitors are much scantier than for H2-receptor antagonists, particularly on
      long-term use.

PMID- 11984129
TI  - Diabetes and the risk of prostate cancer.
AB  - The relation between diabetes and prostate cancer risk was investigated in a
      combined analysis of two hospital-based case-control studies conducted in Italy
      and Greece, between 1985 and 1997. Cases were 608 men with incident prostate
      cancer, and controls were 1008 men admitted to hospital for acute non-neoplastic
      diseases. No material association between diabetes and prostate cancer was
      observed, with a multivariate odds ratio (OR) of 1.07 (95% confidence interval
      (CI) 0.68-1.66). Compared with men without diabetes, there was a non-significant
      increased risk of prostate cancer in those diagnosed with diabetes within the
      last 5 years (OR 2.04), while the ORs were 0.96 and 0.78 respectively for a
      diagnosis of diabetes 5-9 years and > or = 10 years ago.

PMID- 11984130
TI  - Serum levels of beta-hexachlorocyclohexane, hexachlorobenzene and polychlorinated
      biphenyls and breast cancer in Mexican women.
AB  - Information on the association between exposure to beta-hexachlorocyclohexane
      (beta-HCH), hexachlorobenzene (HCB) or polychlorinated biphenyls (PCBs) and the
      incidence of breast cancer is inconclusive. However, exposure to such compounds
      is a public health concern in Mexico and is subject to recent regulation. Serum
      levels of beta-HCH, HCB and PCBs were analysed in 95 histologically confirmed
      breast cancer cases and 95 hospital controls, 20-79 years of age, from Mexico
      City, enrolled between March 1994 and April 1996. After adjusting for established
      risk factors, there was no evidence of a relationship between beta-HCH, HCB and
      PCBs and breast cancer risk (OR for beta-HCH tertile 3 versus tertile 1: 1.05 95%
      CI 0.46-2.40; OR for HCB tertile 3 versus tertile 1: 0.46 95% CI 0.20-1.07; OR
      for PCBs 1.31 95% CI 0.33-5.21 for the high category of exposure). This study
      lends no support to the case for a role for beta-HCH, HCB or PCBs in breast
      cancer aetiology.

PMID- 11984131
TI  - Coffee and tea consumption and cancers of the bladder, colon and rectum.
AB  - Coffee has been observed to be associated weakly or not at all with bladder
      cancer risk, inversely with colon cancer risk, and inconsistently with rectal
      cancer risk. The association between these cancers and consumption of coffee and
      tea was examined in a single case-control study conducted in Ontario, Canada from
      1992 to 1994. A questionnaire was filled out by 927 bladder cancer cases, 991
      colon cancer cases, 875 rectal cancer cases, and 2118 population controls.
      Although bladder cancer risk was not associated with coffee or tea, risk
      estimates associated with coffee among subjects who had never smoked were non
      significantly increased. Colon cancer risk was inversely associated with coffee.
      Relative to those drinking less than 1 cup of coffee per day, the odds ratios
      (OR) for those drinking 1-2 cups was 0.9 (95% CI 0.8-1.1), for those drinking 3-4
      cups was 0.8 (95% CI 0.7-1.0), and for those drinking 5 or more cups was 0.7 (95%
      CI 0.5-0.9); these ORs decreased linearly (P = 0.008). The reduced risk estimates
      were more pronounced with cancer of the proximal colon than the distal colon.
      Rectal cancer risk was not associated with either coffee or tea. Coffee
      consumption was observed to have a different relationship for each of the cancer
      sites and tea consumption was not related to any cancer site.

PMID- 11984132
TI  - Age-specific accuracy of initial versus subsequent mammography screening: results
      from the Ghent breast cancer-screening programme.
AB  - The aim of this study was to determine whether age-related differences in the
      accuracy of mammography breast cancer screening decrease with repeated
      examination. Data from the first 8 years (May 1992 to April 1999) of the Ghent
      breast cancer-screening programme were used for analysis. In total, 28 944
      mammography examinations were included. The referral rate, cancer detection rate,
      positive predictive value, sensitivity and specificity were chosen as performance
      indicators. Values were calculated for women aged 40-49, 50-59 and 60-69 years,
      at initial versus subsequent examinations, respectively. For first examinations,
      overall, performance was much lower for the women in their forties than for the
      older age groups. On subsequent screening, the effect of age disappeared, as
      expected, or was even reversed for the positive predictive value and sensitivity
      of the examination. In the light of the ongoing debate over the eligible age for
      mammography screening, these results support a universal recommendation beginning
      at the age of 40 years.

PMID- 11984133
TI  - Lifestyle-related factors and colorectal polyps: preliminary results from a
      Norwegian follow-up and intervention study.
AB  - Lifestyle-related variables are suggested to play a major role in the development
      of colorectal cancer (CRC). Within a 3-year follow-up and intervention study with
      calcium and antioxidants against growth and recurrence of colorectal polyps,
      supplementary studies were performed in which different aspects of lifestyle were
      examined. Instead of polypectomy at diagnosis, polyps <9 mm were left in situ in
      116 polyp patients (50-76 years, 50% men). After 3 years, all polyps were removed
      and subjected to histology. Two different sets of control groups were included
      (all controls were age- and sex-matched and proven to be free of polyps). We
      applied two different methods in order to assess most exposure variables.
      Generally, in case-control studies, the validity of the study outcomes is high if
      they are similar regardless of choice of controls and methods, since bias due to
      these choices may affect the risk estimates. In contrast, the validity of the
      study outcomes is low if dependent upon these choices. Our preliminary data
      support the theory that different factors may be of importance in different
      stages of the neoplastive formation, and that lifestyle-related factors are
      likely to play a major role in CRC development.

PMID- 11984134
TI  - Sunbathing intentions in Irish people travelling to Mediterranean summer holiday
      destinations.
AB  - As exposure to UV light is thought to be the most significant environmental and
      behavioural risk factor for avoiding skin cancer, we have analysed the sunbathing
      intentions and attitudes of Irish people travelling to Mediterranean and Iberian
      holiday destinations. Ninety per cent of respondents planned to get a suntan on
      their vacation with 44% likely to burn their skin in the process. Although all
      intended to apply sun cream on holiday only 40% would apply >SPF 15. Sixty-four
      per cent planned to sunbathe between 11.00 am and 3.00 pm, with 25% intending to
      spend <5 hours in the sun. One-third of those intending to sunbathe for >6 hours
      per day were aged between 16 and 24 years. Approximately eight out of 10 people
      thought suntans made them feel healthier or attractive. Fifty-six per cent
      regularly checked their moles but men were less likely to check their skin for
      pigment changes. The results provide baseline information on sunbathing attitudes
      of Irish people. They show that while most people feel they adopt a careful
      approach to sunbathing, the experiences and intentions, especially in younger
      people, are influenced by the desirability of a suntan, and reflect a behaviour
      that increases their risk of skin cancer.

PMID- 11984135
TI  - Focusing management in implementing a smoking ban in a university hospital in
      Sweden.
AB  - To explore the impact of various steps when introducing a smoking ban at the
      Karolinska Hospital (1000 beds; 6000 employees) in Stockholm, Sweden, a multiple
      evaluation strategy was performed over 5 years. All heads of clinical departments
      (N = 41) and a random sample of employees (n = 517) and a convenience sample of
      hospital labour managers (n = 17) were separately addressed through questionnaire
      surveys at different time intervals after the introduction of the ban in 1992. An
      observational and interview study completed the follow-up. The implementation
      process was supplemented by a comprehensive information strategy over 5 years.
      The two most important steps during implementation were management support and
      focus on environmental tobacco. The ban was well known at introduction. Heads of
      clinical departments reported a third of staff to be satisfied with the
      restrictions. In contrast, the staff survey revealed 62% to be positive. A shift
      in favour of a radical tobacco-free hospital was perceived during follow-up. Co
      operation between hospital board, heads of clinical departments and local labour
      managers proved successful. The consecutive evaluations served as tools in labour
      management and contributed to staff compliance. A total ban, including the
      selling of tobacco and smoking in the hospital grounds is still to be achieved.

PMID- 11984136
TI  - Global increases in kidney cancer incidence, 1973-1992.
AB  - Reports of increasing rates for kidney cancers in several count prompted this
      analysis of global incidence trends for total kidney cancers and by subsite.
      International incidence data for 5-year periods 1973-1977, 1978-1982, 1983-1987
      and 1988-1992 were obtained from volumes IV to VII of Cancer Incidence in Five
      Continents published by the International Agency for Research on Cancer. The USA
      data for the same 5-year periods were obtained from the Surveillance,
      Epidemiology, and End Results Program of the National Cancer Institute.
      Percentage changes in incidence rates were computed using the relative difference
      between the time periods 1973-1977 and 1988-1992, and annual percentage changes
      in incidence rates were computed using log linear regression. In 1988-1992,
      kidney cancer incidence rates (age-adjusted to the world-standard population)
      were highest in France (16.1/100,000 man-years and 7.3/100,000 woman-years) and
      lowest in India (2.0 and 0.9, respectively). Between 1973-1977 and 1988-1992,
      incidence rates rose among men and women in all regions and ethnic groups, with a
      few exceptions, mostly in Scandinavian countries. The largest percentage increase
      for men was in Japan (171%) and for women in Italy (107%). Rates for renal pelvis
      cancer were less than 1/100,000 person-years in almost all regions in both sexes,
      and the temporal trends were inconsistent. Incidence trends for renal parenchyma
      cancer tracked those for total kidney cancers, and appeared to result from
      increases in the prevalence of risk factors and in use of diagnostic imaging
      procedures.

PMID- 11984137
TI  - Psychological distress in cancer patients: hypothesis of a distress model.
AB  - A substantial body of research suggests links between stress, coping and cancer.
      Research also implicates the immune system as a link between stressful events and
      cancer. The current trend in research in the area of psycho-oncology attempts to
      define the types of stress and coping mechanisms being used in order to identify
      predictors of psychological distress. Based on the available review of
      literature, the impact of distress does seem to play a prominent role in the
      transition from a state of health to that of ill-health or even a terminal event.
      In the light of these studies, a distress model for the cancer patient has been
      hypothesized here.

PMID- 11984138
TI  - Colorectal cancer in an African city population in transition.
AB  - An enquiry has been made on a series of African patients with colorectal cancer
      who were admitted in 1995-1999 to Chris Hani Baragwanath Hospital (3200 beds),
      and who lived in Soweto (population about 1 million), Johannesburg, South Africa.
      In the urban context described, Africans have considerably more advantages, socio
      economically, dietarily and in other respects, than their rural counterparts. The
      126 patients comprised 58 males and 68 females, giving calculated incidence rates
      in their communities for colorectal cancer of 1.7 and 2.0, respectively, per
      100,000 'world' population. In contrast, as indicated in the South African Cancer
      Registry for 1993-1995, the corresponding rates for white males and females were
      24.7 and 19.3, respectively, per 100,000. The proportion of African patients
      under 40 years was 19.0%; but was only 4.0% in the white population. In contrast
      to this major disparity, there was only a minor interethnic disparity regarding
      cancers that are very common in Africans, namely, those of the oesophagus and
      lung. Hence, with ongoing transitional changes - in diet and other respects - the
      relatively high proportion of younger African patients probably indicates a
      rising occurrence of colorectal cancer in the urban African population.

PMID- 11984139
TI  - Dietary sphingolipids in colorectal cancer prevention.
AB  - Sphingolipids are widespread membrane components that are found in all eukaryotic
      cells. They consist of a long chain sphingoid-base, usually sphingosine, which is
      acylated at the 2-amino position, forming a ceramide. All together, sphingolipids
      may represent the most structurally diverse category of lipids in nature. There
      is no known nutritional requirement for sphingolipids. Nonetheless, studies with
      experimental animals have shown that consumption of sphingolipids inhibits colon
      carcinogenesis, reduces serum low-density lipoprotein cholesterol and elevates
      high-density lipoproteins, which suggest that they are 'functional' components of
      food. In animal models (CF1 mice) sphingomyelin supplementation reduces the
      number of aberrant colonic crypt foci by approximately 70% and, with longer
      feeding, reduces the number of colonic adenocarcinomas. A possible mechanism of
      action of sphingolipids in suppressing colon carcinogenesis is that exogenously
      supplied sphingolipids bypass a sphingolipid signalling defect that is important
      in cancer (for example, a loss of cellular sphingomyelin turnover to produce
      ceramide and sphingosine). Indirect evidence suggests that sphingolipids can
      inhibit colon cancer in humans: sphingosine and ceramide induce apoptosis in a
      human adenocarcinoma cell line and feeding sphingolipids to Min mice reduces the
      number of colon tumours.

PMID- 11984141
TI  - But baby, it's cold outside.

PMID- 11984142
TI  - Genetically modified interferon: is there a consensus yet?
AB  - The treatment of patients with chronic hepatitis C virus infection has evolved
      during the last decade from interferon monotherapy to combination therapy with
      interferon and ribavirin. National and international guidelines recommend either
      6 or 12 months of interferon/ribavirin combination therapy depending on the pre
      treatment virological status of the patient. However, the choice for second-line
      treatment of patients who do not achieve sustained viral clearance with
      combination therapy has yet to be defined. This commentary examines previously
      published studies of the use of consensus interferon for hepatitis C virus
      infected patients. The characteristics of the treated populations and response to
      treatment are examined. The current and potential roles for this type of
      interferon in the treatment of hepatitis C virus infection are considered.

PMID- 11984143
TI  - Can risk stratification improve the management of acute upper-gastrointestinal
      bleeding?
AB  - Acute upper-gastrointestinal bleeding is a common indication for emergency
      admission to hospital. Risk-stratification scores have been devised to identify
      patients at risk of re-bleeding or death, but these have usually required both
      clinical and endoscopic assessment. Two recent studies have employed clinical
      criteria alone to identify low-risk patients that may not require admission or in
      patient endoscopy. While each of these studies has individual merit, both are
      unable to answer the question of whether risk stratification improves health
      outcomes or resource use in acute gastrointestinal haemorrhage. They will
      nevertheless help the development of guidelines that enable patients to be
      managed more efficiently and outcomes to be compared more fairly.

PMID- 11984144
TI  - Consensus interferon for chronic hepatitis C patients with genotype 1 who failed
      to respond to, or relapsed after, interferon alpha-2b and ribavirin in
      combination: an Italian pilot study.
AB  - OBJECTIVE: To evaluate the long-term efficacy of consensus interferon in the
      treatment of chronic hepatitis C patients with genotype 1 who failed to respond
      to, or relapsed after, combination therapy with interferon alpha-2b and
      ribavirin. DESIGN: Open label pilot study. METHODS: Twenty-four chronic hepatitis
      C outpatient non-responders to (12 cases), or relapsers after (12 cases),
      standard combination therapy were treated with consensus interferon (9 microg
      five times per week) for 36 weeks. The patients were followed up for a further 24
      weeks. The primary end-point of the study was the rate of sustained virological
      response. RESULTS: Sustained virological response was observed in 33% of previous
      non-responders and in 42% of previous relapsers. Improvement of the histological
      score was documented in 80% of previous non-responders and in all previous
      relapsers who showed undetectable levels of hepatitis C virus RNA at the end of
      treatment. Logistic regression analysis showed that sustained virological
      response was associated with a hepatitis C viral load of 2 x 106 copies/ml or
      less, with an inflammation score of 7 or less and with an estimated duration of
      disease of 10 years or less. The treatment was well tolerated with an 83%
      compliance. CONCLUSIONS: Consensus interferon given at a dose of 9 microg five
      times per week for 36 weeks may offer a good chance of sustained virological
      response in a subset of patients who failed to respond to, or relapsed after,
      standard combination therapy. However, a larger randomized trial is required to
      assess the efficacy of consensus interferon before its use can be advocated for
      the treatment of such patients.

PMID- 11984145
TI  - The antibody response to hepatitis B virus vaccination is negatively influenced
      by the hepatitis C virus viral load in patients with chronic hepatitis C: a case
      control study.
AB  - The purpose of this work was to evaluate in a case-control study the
      immunogenicity of a recombinant hepatitis B virus (HBV) vaccine in patients with
      chronic hepatitis C. Seventy-seven patients with histologically proven chronic
      hepatitis C without cirrhosis were included in a prospective trial and matched
      for sex and age to 231 healthy adult subjects. Recombinant HBV vaccine was
      administered at a dose of 20 microg at months 0, 1 and 2. The definition of
      'responder to vaccination' was anti-HBs titre > 10 mIU/ml after the three
      injections. Forty-nine (63.6%) chronic hepatitis C patients were responders to
      vaccination, compared with 217 (93.9%) controls (P < 0.0001). After the three
      injections, anti-HBs titres were 156 +/- 260 and 615 +/- 435 mIU/ml (P < 0.0001),
      respectively. Chronic hepatitis C patients who were non-responders to vaccination
      had significantly higher viral load than responders to vaccination. Moreover, a
      negative correlation was observed between viral load and anti-HBs concentration
      (r = -0.36, P = 0.003). No significant side effects were observed. There was no
      effect of vaccination on alanine aminotransferase (ALT) levels and hepatitis C
      virus (HCV) viral load during or after vaccination. In multivariate analysis, the
      main predictive factors of response to HBV vaccine were absence of anti-HCV
      antibodies (OR = 7.65, P < 0.0001), weight < 75 kg (OR = 1.99, P < 0.035), and
      age < 50 years (OR = 1.58, P < 0.082). Our results suggest that viral load seems
      to negatively influence the response to HBV vaccine.

PMID- 11984146
TI  - Pharmacokinetic study of esomeprazole in patients with hepatic impairment.
AB  - OBJECTIVE: To evaluate the pharmacokinetics and safety of esomeprazole (Nexium),
      the S-isomer of omeprazole, after repeated oral dosing in patients with hepatic
      impairment. DESIGN: Single-centre, open-label one-way study. METHODS: Twelve
      patients (aged 40-60 years) with mild to severe hepatic impairment received once
      daily oral esomeprazole 40 mg for 5 days. Serial blood samples were drawn up to
      24 h post-dose on day 5 to determine plasma levels of esomeprazole and its
      metabolites. Pharmacokinetic parameters were compared with an historical control
      group of 36 gastro-oesophageal reflux disease (GORD) patients (aged 29-58 years)
      with normal hepatic function. RESULTS: Esomeprazole was absorbed rapidly (mean
      maximum plasma concentration (Cmax) 6.1 micromol/l, mean time to Cmax (tmax) 1.9
      h) and eliminated rapidly (mean plasma elimination half-life (t1/2) 2.1 h).
      Elimination of its pharmacologically inactive sulphone and hydroxy metabolites
      was more gradual. Patients with mild hepatic impairment had area under the plasma
      concentration-time curve during the dosage interval (AUCtau) and t1/2 values
      largely within the range of the control group. In patients with moderate hepatic
      impairment, t1/2 values were similar and AUCtau was slightly higher than in
      controls, whereas both parameters were increased in patients with severe hepatic
      impairment. The mean ratios of esomeprazole AUCtau, Cmax and t1/2 values in
      patients with and without hepatic impairment were 1.8, 1.3 and 1.3, respectively.
      CONCLUSIONS: The steady-state pharmacokinetics of esomeprazole were not altered
      substantially by mild or moderate hepatic impairment; however, plasma levels of
      esomeprazole were elevated in severe cases. Thus, dose adjustment appears
      unwarranted in mild or moderate hepatic impairment, but may be required in some
      severely impaired patients. Esomeprazole was tolerated well across the spectrum
      of hepatic impairment.

PMID- 11984147
TI  - Three-year prospective validation of a pre-endoscopic risk stratification in
      patients with acute upper-gastrointestinal haemorrhage.
AB  - OBJECTIVE: To assess the accuracy of a risk stratification that is used at
      initial assessment to identify groups with increased risk of mortality and
      requirement for urgent treatment intervention. DESIGN: Prospective assessment of
      risk stratification in consecutive patients with acute upper-gastrointestinal
      haemorrhage. METHODS: Over a 3-year period, 1349 consecutive patients with acute
      upper-gastrointestinal haemorrhage presenting to a single teaching hospital were
      prospectively risk stratified before endoscopy and followed up for outcome. MAIN
      OUTCOME MEASURES: Two-week, all-cause mortality, re-bleeding, and need for urgent
      treatment intervention. RESULTS: Stratification within the high-risk group
      predicted a significant increased risk of 2-week, all-cause mortality (P < 0.001)
      when compared with intermediate- and low-risk patients (11.8%, 3% and 0%,
      respectively), re-bleeding (P < 0.001) (44.1%, 2.3% and 0%, respectively), and
      need for urgent treatment intervention (P < 0.001) (71%, 40.6% and 2.6%,
      respectively). CONCLUSIONS: Over a 3-year period, medical staff at this
      institution have routinely used this risk stratification, which identifies groups
      of patients at high and low risk of mortality, re-bleeding and need for urgent
      treatment intervention following acute upper-gastrointestinal haemorrhage. Use of
      this risk stratification should allow targeting of more intensive treatment where
      it might be of most benefit. Those patients at lowest risk from outpatient
      management are also identified.

PMID- 11984148
TI  - Eosinophil infiltration and activation at the gastric ulcer margin in rats.
AB  - BACKGROUND: Recruitment and activation of eosinophils have been studied intensely
      in asthma and other allergic diseases. Less is known about the infiltration and
      behaviour of eosinophils during gastric ulcer healing. AIM: To examine the tissue
      infiltration and activation of eosinophils in the ulcer margin at different time
      points after ulcer induction (days 1-15). METHODS: Eosinophil peroxidase (EPO)
      staining and transmission electron microscopy (TEM) were used to observe
      eosinophil infiltration and activation in rats with acetic-acid-induced ulcer in
      the oxyntic mucosa. The distribution of macrophages was evaluated by
      immunocytochemistry using the macrophage-specific antibodies ED1 and ED2.
      RESULTS: There was a prominent increase in eosinophils around the ulcer margin at
      day 1 after ulcer induction, which peaked at day 5. TEM revealed characteristic
      signs of eosinophil activation, including cytolysis and piecemeal degranulation.
      Eosinophil cytolysis was the major form of activation, seen most frequently at
      day 5. A few scattered apoptotic eosinophils could also be observed. In normal
      controls and sham-operated rats, activated eosinophils were detected rarely. The
      distribution pattern of infiltrated eosinophils closely resembled that of
      macrophages at the ulcer margin. However, in the central part of the granulation
      tissue (at day 5) only macrophages could be found. CONCLUSIONS: There is marked
      infiltration and signs of activation of eosinophils together with macrophages at
      the margin of newly formed ulcers.

PMID- 11984149
TI  - Validated accuracy of a novel urea breath test for rapid Helicobacter pylori
      detection and in-office analysis.
AB  - BACKGROUND: A novel 14C-urea breath test (UBT) was developed to detect the
      presence of Helicobacter pylori by bench analysis in office, enabling the
      practitioner to readily reveal H. pylori infection. AIM: To validate the novel
      UBT (Heliprobe) versus conventional UBT. METHODS: Pretreatment (n = 203) and post
      treatment (n = 147) detection of H. pylori. Additional tests with encapsulated
      14C-urea (n = 37) were validated. After intake of liquid or encapsulated 14C
      urea, exhaled 14CO2 in breath was trapped in benzethoniumhydroxide/ethanol, or
      adsorbed to LiOH-soaked pads on a dry cover surface (Heliprobe BreathCard). The
      amount of adsorbed 14C was detected using a beta-scintillator or two Geiger
      Muller counters operating in parallel (Heliprobe Analyzer). RESULTS: For
      pretreatment detection, we found full concordance between the UBTs, with 100%
      sensitivity and specificity (CI 95-100% and 97-100%, respectively) and strong
      agreement (r = 0.80, CI 0.75-0.85; kappa = 1, CI 0.86-1.14; P < 0.0001).
      Similarly, for post-treatment follow-up detection, sensitivity and specificity
      were 100% (CI 85-100% and 97-100%, respectively) with significant agreement (r =
      0.48, CI 0.34-0.59; kappa = 1, CI 0.84-1.16; P < 0.0001). The use of encapsulated
      14C-urea did not change agreement between the tests. Sensitivity and specificity
      were 100% (CI 72-100% and 87-100%, respectively) with strong agreement between
      the tests (r = 0.71, CI 0.50-0.84; kappa = 1, CI 0.68-1.32; P < 0.0001).
      CONCLUSION: The novel Heliprobe UBT, with either liquid or encapsulated 14C-urea,
      seems equi-efficacious to conventional UBT in fulfilling its role as the non
      invasive gold standard for detection of H. pylori.

PMID- 11984150
TI  - Helicobacter pylori infection is unlikely to be transmitted between partners:
      evidence from genotypic study in partners of infected patients.
AB  - INTRODUCTION: We postulated that the oro-oral route of transmission between
      spouses could be an important route of transmission of Helicobacter pylori. AIMS:
      To estimate the prevalence of different genotypes of H. pylori as distinguished
      by the polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method in our local population, and to compare the genotypes of H. pylori
      isolated from patients and their spouses. METHODS: Gastric biopsies were obtained
      from 183 dyspeptic patients during endoscopy. PCR for H. pylori was carried out
      using the uceC gene for amplification, and PCR products were digested further for
      RFLP analysis using the enzyme MboI. Spouses of H. pylori-positive index cases
      were screened for the infection using serological testing; if found to be
      positive serologically, endoscopy and gastric biopsies were performed for
      genotypic study of the micro-organism. For couples with indistinguishable H.
      pylori strain on RFLP with restriction endonuclease MboI, the process of RFLP was
      repeated with digestion of the PCR products using restriction endonuclease HhaI.
      RESULTS: We established our PCR technique to be 89.5% sensitive and 95.5%
      specific. Eighty-nine subjects were found to be H. pylori positive by PCR, and
      eight different genotypic strains were found according to our RFLP analysis. Two
      genotypes accounted for 80.8% of the cases. Sixteen of 31 spouses tested
      serologically for H. pylori were positive. All 13 spouses who agreed to undergo
      endoscopy were PCR positive for H. pylori. Five couples shared indistinguishable
      H. pylori genotypes, but this strain was also the commonest genotype in our local
      population, as based on RFLP with restriction endonuclease MboI. Further RFLP on
      the PCR products on these five couples using restriction endonucleases HhaI
      showed that the H. pylori isolated from these five couples were of different
      strains. CONCLUSION: The oro-oral route of transmission between spouses is
      unlikely to be an important mode for H. pylori infection.

PMID- 11984151
TI  - A case-control study of childhood environmental risk factors for the development
      of inflammatory bowel disease.
AB  - OBJECTIVE: To clarify the relationship between childhood environment and the risk
      of subsequent development of Crohn's disease or ulcerative colitis. DESIGN AND
      OUTCOME MEASURES: A case-control study, assessing the risk of inflammatory bowel
      disease in relation to a series of historical and serological markers of
      childhood circumstance, analysed using the maximum likelihood form of conditional
      logistic regression. SETTING: District general hospital (secondary care
      institution). PARTICIPANTS: Subjects with Crohn's disease (n = 139) or ulcerative
      colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with
      an outpatient control. RESULTS: Helicobacter seroprevalence was substantially
      reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative
      colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative
      association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01
      0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI,
      1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91).
      There was no association between hepatitis A seroprevalence and either disease.
      CONCLUSION: The findings are consistent with the hypothesis that improved
      childhood living conditions are associated with increased risk of Crohn's
      disease. The study confirms that the negative association between appendectomy
      and ulcerative colitis relates primarily to events in childhood. Overall, the
      findings strongly support the assertion that childhood environment is an
      important determinant of the risk of inflammatory bowel disease in later life,
      with quite distinct risk factors for ulcerative colitis and Crohn's disease.

PMID- 11984152
TI  - Predominance of caecal injury in a new dextran sulphate sodium treatment in rats:
      histopathological and fermentative characteristics.
AB  - OBJECTIVES: Cyclic administrations of dextran sulphate sodium (DSS) alternating
      with distilled water usually induce chronic colitis after a few weeks. In order
      to obtain stable chronic colitis (without recovery or relapse) in a few days, a
      new continuous DSS treatment was tested and characterized. Short-chain fatty
      acids (SCFAs), which remain poorly documented in experimental colitis, were also
      investigated. METHODS: Thirty-six Sprague-Dawley rats were treated with 5% DSS
      for 7 days (DI) followed by 3% DSS for 7 days (DM) or 14 days (DF). Control rats
      received only water. Inflammatory injuries in the caecum and the colon were
      assessed by macroscopic (colon length, caecum weight, damages score) and
      histological parameters. SCFAs (acetate, propionate, butyrate) were quantified
      individually in caecal, proximal and distal contents. RESULTS: Macroscopic and
      histological observations revealed that this continuous DSS treatment induced
      acute inflammation (DI) followed rapidly by chronic active colitis. The latter
      was uncommonly predominant in the caecum and the distal colon, and was also
      associated with some fermentative disturbances. Caecal SCFA concentrations
      decreased with DSS at DI and DM. The molar ratio of caecal butyrate increased
      with DSS. Acetate decreased in the colon while propionate increased. CONCLUSION:
      This new DSS treatment is able to induce in a few days stable chronic
      inflammation with caecal and distal predominant injuries, and mild fermentative
      caeco-colonic alterations. This model could contribute to the study of potential
      anti-inflammatory effects of prebiotics.

PMID- 11984153
TI  - Social position of adolescents with chronic digestive disorders.
AB  - OBJECTIVE: To investigate the consequences of having a chronic digestive disorder
      on the social position of adolescents. METHODS: Five diagnostic groups, including
      inflammatory bowel disease (IBD), chronic liver diseases, congenital digestive
      disorders, coeliac disease and food allergy (total n = 758, ages 12-25 years),
      were each compared with a population-based control group in a multicentre study
      using a cross-sectional design. Social position was assessed by a mailed
      questionnaire measuring 24 aspects, categorized as education, leisure activities,
      friendship, labour participation, financial situation, partnership and sexuality.
      RESULTS: Eight aspects of social position were found to be affected negatively by
      one or more chronic digestive diseases: absence from school due to illness, going
      out, having a paid job, needing re-education in order to get a job, getting
      benefits as main income source, encountering bottlenecks in establishing
      financial commitments, having self-confidence in making a pass at someone, and
      restrictions in making love. Adolescents with chronic liver disease and IBD were
      found to experience more restrictions in social position. Adolescents with food
      allergy and congenital digestive disorders appear to experience some
      restrictions, but to a lesser degree, and adolescents with coeliac disease do not
      appear to have any problems regarding social position compared with controls.
      CONCLUSION: The social position of adolescents is affected negatively by having a
      chronic digestive disease, in particular chronic liver disease and IBD. Negative
      consequences occur in education, leisure activities, labour participation,
      financial situation, partnership and sexuality.

PMID- 11984154
TI  - Duodenal ulcer and pancreatitis associated with pancreatic arteriovenous
      malformation.
AB  - Arteriovenous malformation (AVM) of the pancreas is a rare condition that may
      cause severe gastrointestinal bleeding. We describe a 54-year-old man with a 7
      year history of recurrent duodenal ulcer due to AVM in the pancreatic head. We
      recommended pancreatoduodenectomy because of recurrent haemorrhage from the
      duodenal ulcer, but the patient refused surgery on several occasions. He was
      admitted to our hospital complaining of severe upper abdominal pain radiating to
      the back and was diagnosed with acute pancreatitis. He agreed at that stage to
      the surgical treatment. The resected specimen contained a highly vascular
      malformation in the pancreatic head and ulceration in the adjacent descending
      duodenum. Histopathological examination revealed numerous vascular structures
      with dilated and tortuous vessels in the pancreatic head, confirming the presence
      of AVM. Moreover, oedema, inflammatory cell infiltration, haemorrhage and
      necrosis were evident, confirming the presence of acute pancreatitis.

PMID- 11984155
TI  - Rhabdomyolysis and severe haemolytic anaemia, hepatic dysfunction and intestinal
      osteopathy due to hypophosphataemia in a patient after Billroth II gastrectomy.
AB  - Hypophosphataemic syndromes lead to appreciable morbidity and mortality. A
      deficiency or lack of phosphate leads to tissue hypoxia and disruption of
      cellular function, which may cause severe clinical complications. We present
      various manifestations of hypophosphataemia; in all cases, diagnosis was delayed
      due to lack of follow-up. We present the case of a patient with rhabdomyolysis,
      severe haemolytic anaemia, hepatic dysfunction and intestinal osteopathy due to
      hypophosphataemia complicated by gastric Billroth II anastomosis surgery. We also
      review the literature concerning hypophosphataemic conditions. In conclusion, the
      determination of serum calcium and phosphate levels should be included in the
      routine follow-up of Billroth II anastomosed patients.

PMID- 11984156
TI  - Hepatitis associated with Chinese herbs.
AB  - Traditional Chinese herbal medicines are widely available in Western society and
      are popular as a form of 'natural' alternative medicine. Their use is increasing,
      as they are perceived to be free of side effects, but they remain largely
      unregulated. We describe two patients who suffered severe hepatitis, one of whom
      died, after taking Chinese herbal remedies for minor complaints. We also review
      the English-language literature on hepatitis associated with Chinese herbs. Two
      products appear to be implicated frequently: Jin bu huan was taken by 11
      patients, and Dictamnus dasycarpus was taken by six patients, including both
      fatal cases. It is difficult to provide conclusive evidence of what caused
      hepatitis, as these products are mixtures that may contain adulterants. These
      cases highlight not only the potential dangers of these products to consumers but
      also the need for greater control of their manufacture and use.

PMID- 11984157
TI  - Hepatitis B associated fulminant polyarteritis nodosa: successful treatment with
      pulse cyclophosphamide, prednisolone and lamivudine following emergency surgery.
AB  - For hepatitis B virus associated polyarteritis nodosa, alpha interferon and
      plasma exchanges have been proposed to be the first-line treatment. We report a
      case of hepatitis B surface antigen (HBsAg)-positive fulminant polyarteritis
      nodosa with predominant gastrointestinal involvement who showed good response to
      pulse cyclophosphamide, prednisolone, and lamivudine therapy. The patient, a 22
      year-old man, presented with a short history of epigastric pain. Initial upper
      gastrointestinal endoscopy revealed gastritis and duodenal erosions. His pain did
      not respond to H2-receptor antagonists. He had slightly impaired liver function
      tests, and was HBsAg and hepatitis B e antigen (HBeAg) positive. Around 3 weeks
      after initial presentation, he developed massive gastrointestinal haemorrhage
      requiring resuscitation and emergency laparotomy. Microscopic examination of the
      resection specimens revealed necrotizing vasculitis of small and medium-sized
      arteries in the submucosa compatible with polyarteritis nodosa. The patient was
      treated with pulse cyclophosphamide and prednisolone, with lamivudine being added
      when he showed an acute rise in liver enzymes. He subsequently developed HBeAg
      seroconversion, and remained well 18 months after cessation of all
      immunosuppressives. We believe that the efficacy of pulse cyclophosphamide,
      prednisolone, and lamivudine in the treatment of hepatitis B virus associated
      polyarteritis nodosa, especially in comparison with interferon and plasma
      exchanges, deserves further evaluation.

PMID- 11984158
TI  - Transjugular intrahepatic portosystemic shunt by direct transcaval approach in
      patients with acute and hyperacute Budd-Chiari syndrome.
AB  - When Budd-Chiari syndrome (BCS) is due to occlusion of all three hepatic veins,
      the standard transjugular intrahepatic portosystemic shunt (TIPS) technique can
      be extremely laborious. A feasible alternative is to use the direct transcaval
      approach, by which a shunt can be created directly between the intrahepatic
      inferior vena cava and the portal vein. We describe two patients (one with acute
      BCS and one with hyperacute BCS) who were successfully managed with this modified
      technique. Both patients recovered; one of them underwent elective liver
      transplantation 15 months after the procedure, whereas the other still had good
      hepatic function and a patent stent 24 months after the procedure. We conclude
      that, in selected patients with acute and hyperacute BCS, placement of a TIPS by
      the direct transcaval approach is a rapid and effective emergency procedure,
      which can either be curative or function as a bridge for elective liver
      transplantation.

PMID- 11984159
TI  - Neuromas of the extrahepatic bile ducts as a cause of obstructive jaundice.
AB  - We present four cases of extrahepatic bile duct neuromas causing obstructive
      jaundice. Two patients with neuromas localized in the hepatic duct had no
      evidence of gallstones or history of previous surgery. In these subjects, partial
      resection of the common bile duct and cholecystectomy was followed by hepatico
      jejunostomy with Roux-en-Y reconstruction. In another patient, 7 years after
      cholecystectomy, a neuroma localized in the hepatic duct was treated by insertion
      of a T-tube. In the fourth patient, 9 years after laparoscopic cholecystectomy,
      partial common bile duct resection and Roux-en-Y hepatico-jejunostomy was
      performed. In all cases, the correct diagnosis of this very rare cause of
      extrahepatic bile duct obstruction was established postoperatively.

PMID- 11984160
TI  - Caroli's disease diagnosed by magnetic resonance cholangiopancreatography.

PMID- 11984161
TI  - Is our specialty special?

PMID- 11984162
TI  - The benefits and challenges of the computerized electronic medical record.
AB  - Data from aggregate individual patient records can be gathered to answer many
      clinical and nursing research questions about quality assurance and resource
      allocation, assisting in the measurement and evaluation of patient care outcomes.
      The use of standardized nursing language, large integrated computer databases,
      and information management processes provide for the use of patient-specific data
      and information to facilitate patient care. The use of aggregated data can also
      facilitate the comparison of nursing practice across populations, demonstrate and
      project nursing care trends, serve as a financial and legal record, aid in
      clinical research, support decision analysis, and guide professional and
      organization performance improvement.

PMID- 11984163
TI  - Anthrax: is there a risk of cross-infection during endoscopy?
AB  - Bacillus anthracis is a large, gram-positive, spore-forming bacterium responsible
      for human anthrax. Review of the medical literature indicates specific instrument
      reprocessing instructions addressing the prevention of B. anthracis transmission
      are limited. Although nosocomial anthrax infection has not been reported, strict
      adherence to well-established instrument reprocessing guidelines for cleaning and
      high-level disinfection is recommended to prevent patient-to-patient transmission
      of B. anthracis (or any other pathogen) via gastrointestinal endoscopes or
      bronchoscopes. All liquid chemical sterilants labeled for high-level disinfection
      of endoscopes would be expected to destroy B. anthracis. Additional instrument
      cleaning or disinfection procedures appear to be unnecessary. Reprocessing the
      endoscope immediately following the procedure is emphasized.

PMID- 11984164
TI  - Biliary and pancreatic stents.
AB  - Endoscopic retrograde cholangiopancreatography is one of the most challenging and
      demanding procedures performed in endoscopy units. Many endoscopy staff nurses
      become overwhelmed by the complexity of patient management and the realm of
      equipment necessary in providing endoscopic therapy for patients with biliary and
      pancreatic disease. The case of Ray, a 45-year-old patient, is used in this
      article to demonstrate the current value of biliary stenting and its potential
      impact on a patient's life. An understanding of the indications for and uses of
      stents in the treatment of biliary occlusion and pancreatic disease will provide
      a foundation for those assisting in endoscopic retrograde
      cholangiopancreatography.

PMID- 11984165
TI  - Frequency of operative trauma to anal sphincters: evaluation with endoanal
      ultrasound.
AB  - Sphincter trauma after anorectal surgery is usually asymptomatic. Frequency of
      trauma cannot be established with the clinical examination only. The frequency of
      operative sphincter defects and their correlation with disorders of continence
      was evaluated with the endoanal ultrasound. This study includes 123 subjects who
      had undergone anorectal surgery in the past and were examined with endoanal
      ultrasound for various indications such as continence disorders, recurrent
      fistula, idiopathic perineal pain, or simple postoperative follow-up. No subjects
      had isolated external anal sphincter defects. Nineteen of 123 patients (15%) had
      minor or major continence disorders, 55 patients (45%) had no sphincter defects,
      42 (34%) had only internal anal sphincter (IAS) defects, and 26 (21%) had
      simultaneously external and internal anal sphincter (EAS) defects. The incidence
      of IAS and EAS trauma after Milligan-Morgan hemorrhoidectomy was 1/18 (5.5%) and
      0/18 respectively; after fistula repair, 24/42 (57%) and 12/42 (29%); and after
      anal dilatation, 13/17 (76%) and 4/17 (24%). Sixteen of 26 patients (62%) with
      EAS trauma and 51/68 patients (75%) with IAS trauma did not report any disorders
      of continence. In patients with two or more operations, the frequency of IAS
      trauma was 74%, 30% for EAS trauma, and 26% for continence disorders.

PMID- 11984166
TI  - Therapeutic bronchoscopy: endobronchial laser resection and airway stenting.
AB  - Lung cancer is the leading cause of cancer death among both men and women. About
      30% of lung cancers cause obstruction of the major bronchus leading to severe
      complications such as postobstructive pneumonia, hemoptysis, and progressive
      dyspnea. Endobronchial laser treatment and airway stenting is an interventional
      pulmonary treatment offered to patients with lung tumors that obstruct the main
      airways. This article will provide an overview of endobronchial laser resection
      and airway stenting with a particular focus on procedural techniques and care of
      the patient.

PMID- 11984167
TI  - Complementary health care practices: what is homeopathy?

PMID- 11984169
TI  - Research in practice: formulating a research question.

PMID- 11984168
TI  - Leading the way: nix the nails.

PMID- 11984173
TI  - Ten myths and facts about hospice care.

PMID- 11984174
TI  - CMS updates HIM-11.

PMID- 11984175
TI  - Phlebotomy tools of the trade.

PMID- 11984176
TI  - Assessing behavioral health using OASIS: Part 1: Depression and suicidality.
AB  - This article is the first of a two-part series on assessing behavioral health in
      adult and elderly patients using OASIS. Direct questioning about emotional and
      behavioral symptoms in addition to observation, reports from family members, and
      input from other team members are used. This approach improves assessment
      information and increases nurse confidence and accuracy when making referrals for
      further psychiatric evaluation and treatment.

PMID- 11984177
TI  - Illuminating the experience of student precepting: insights and narratives from
      home care nurses.
AB  - Home care nurses precepting students eloquently describe the rewards and
      frustrations associated with this role. Narratives illustrating the experience
      give voice to home care nurses. Lessons learned provide planning suggestions and
      insight for nurses who might be contemplating this role as well as for student
      and faculty planning.

PMID- 11984178
TI  - Diabetes pattern management: the key to diabetes self-management and glycemic
      control.
AB  - Technological advances in home blood glucose monitors have no practical value
      unless the test results are recorded and used for pattern management. This
      systematic approach is central to the plan of care for patients with diabetes.
      Pattern management helps patients, caregivers, and referring physicians identify
      patterns in blood glucose readings, so treatment and/or lifestyle changes can be
      made without delay.

PMID- 11984179
TI  - Partners in healing: home care, hospice, and parish nurses.
AB  - A creative way to support patients in self-care strategies is to work with the
      parish nurse as a practice partner. This article shares approaches and innovative
      ideas on how home care and hospice nurses can work effectively with parish
      nurses.

PMID- 11984180
TI  - Techniques for stabilizing urinary catheters.

PMID- 11984181
TI  - The Joint Commission home care contracted services survey process.

PMID- 11984182
TI  - Accomplishing quality of life in end-stage heart failure: a hospice
      multidisciplinary approach.
AB  - The literature addresses using multidisciplinary teams to manage outpatient heart
      failure patients to reduce hospital readmission rates, increase functional
      capacity, and improve quality of life. This article shows how a multidisciplinary
      team can be used for these same patients in a hospice home care program.

PMID- 11984183
TI  - In diabetic management--control is the goal.

PMID- 11984187
TI  - The fuzzy math of Medicare home care cuts.

PMID- 11984188
TI  - HIPAA...one size does not necessarily fit all.
AB  - HIPPA is an important piece of legislation that will affect agency operations,
      clinical practice, regulatory compliance, and patient care. This article gives
      you the foundation needed to understand how HIPPA will affect you!

PMID- 11984189
TI  - New initiatives to address the nursing shortage.

PMID- 11984190
TI  - Fifteen ways to enhance client outcomes by using your registered dietitian.

PMID- 11984191
TI  - Assessing behavioral health using OASIS: part 2: cognitive impairment,
      problematic behaviors, and anxiety.
AB  - This article is the second of a two-part series on assessing behavioral health in
      adult and elderly home care patients using OASIS. Part 1 presented an assessment
      approach for depressive symptoms and suicidality. This article presents the
      assessment of cognitive impairment, problematic behaviors, and anxiety using
      OASIS as a framework and stresses the importance of direct questioning. Case
      scenarios and guidelines for referral for further evaluation and possible
      treatment are provided.

PMID- 11984192
TI  - An exploratory study of nurse bag use by home visiting nurses.
AB  - Although the bag of the home care nurse is functional and historical, there is
      limited information in the literature about its use and nurses' preferences. This
      study analyzes how the bag is used, and examines comfort issues and preferences
      nurses have for this valuable tool. Implications for design and features are
      gained from this research as well as specific features to seek when choosing this
      important ergonomic tool.

PMID- 11984193
TI  - Positive inotropic drug infusions for patients with heart failure: current
      controversies and best practice.
AB  - Patients who experience severe symptoms of heart failure and repeated
      hospitalizations for exacerbations may benefit from positive inotropic drug
      infusion therapy such as dobutamine or milrinone. This article provides an
      overview of inotropic drug delivery in the home including current controversies
      and best practices to ensure safe home care policies and practice.

PMID- 11984194
TI  - Defining and monitoring indwelling catheter-related urinary tract infections.
AB  - Defining and monitoring infection rates in home care is of major importance with
      the implementation of Adverse Event Outcome Reports. This study identifies the
      collective effort of home care quality improvement nurses in defining standard
      indicators for urinary tract infections and the ways to monitor these infections
      within and across home care agencies for evaluation and benchmarking.

PMID- 11984195
TI  - Using OASIS data to improve skin care.
AB  - Using the FOCUS-PDCA process, this article outlines an early intervention project
      focusing on improving patient interventions for skin care using OASIS data.

PMID- 11984196
TI  - Frequently asked questions about CHAP accreditation.

PMID- 11984197
TI  - Medicare part B changes affect wound care planning for 2002.

PMID- 11984198
TI  - HHNA Research Committee update.

PMID- 11984199
TI  - Point-of-care technology: are we ready?

PMID- 11984202
TI  - Clinical significance, detection, and medical treatment for peripheral arterial
      disease.

PMID- 11984203
TI  - Prevalence of lipid-lowering therapy at cardiac rehabilitation entry: 2000 versus
      1996.

PMID- 11984204
TI  - A comparison of methods for the calculation of peak oxygen uptake in patients
      with heart failure.

PMID- 11984205
TI  - How should peak oxygen uptake be expressed in heart failure?

PMID- 11984206
TI  - Using the Duke Activity Status Index in heart failure.

PMID- 11984207
TI  - The metabolic demand of golf in patients with heart disease and in healthy
      adults.
AB  - PURPOSE: To evaluate the metabolic cost of golf, while pulling a cart, in a group
      of patients with heart disease (HD) and healthy adults with a wide range of
      functional capacities. METHODS: Twenty male golfers aged 49 to 78 years
      participated in this study. All participants underwent a graded exercise test
      (GXT) with expired gas analysis to determine functional capacity. Each patient
      with HD (n = 10) was matched with a healthy adult of similar age. Each pair
      completed 9 holes of golf while pulling a cart, during which oxygen consumption
      was monitored continuously via the Cosmed K4b2 portable unit. RESULTS: The
      average metabolic equivalent (MET) value (1 MET = 3.5 mL x kg(-1) x min(-1))
      (mean +/- SEM) for 9 holes of golf in this group of men with HD (4.1 +/- 0.1
      METs) was similar to that previously reported value of 4.3 METs. Whereas the
      average MET responses were similar between the groups, when expressed relative to
      peak oxygen consumption, on average, patients with HD worked at a significantly
      higher percentage of their functional capacity (57 +/- 2.7%) compared to the
      healthy adults (46 +/- 2.6%). Some patients with HD exceeded 100% of GXT MET
      level during golf. In contrast, some healthy adults failed to reach 60% of GXT
      MET level during golf. CONCLUSIONS: Based on these data, walking the golf course
      while pulling a cart appears to provide an adequate training stimulus for most
      patients with HD. However, some lower fit patients with HD (< 8 METs) are in
      danger of exceeding a safe level and should be encouraged to monitor intensity on
      the golf course and consider using a motorized cart. For most individuals who are
      more fit (functional capacity > or = 8 METs), golf does not appear to provide the
      stimulus generally associated with improvement in functional capacity.

PMID- 11984208
TI  - Medically directed home-based exercise using a stepping device with ECG telemetry
      monitoring in patients with previous myocardial infarction.

PMID- 11984209
TI  - Exercise training improves outcomes of a dyspnea self-management program.
AB  - PURPOSE: The purpose of this study was twofold: (1) to determine whether exercise
      training adds to the benefit of a dyspnea self-management (DM) program; and (2)
      to determine if there is a "dose response" to supervised exercise training (0, 4,
      or 24 sessions) in dyspnea, exercise performance, and health-related quality of
      life. METHODS: Subjects with chronic obstructive pulmonary disease (n = 103, 46
      men, 57 women; age 66 +/- 8 years; forced expiratory volume in 1 second 44.8 +/-
      14% predicted) were randomized to DM, DM-exposure, or DM-training. Dyspnea self
      management included individualized education about dyspnea management strategies,
      a home-walking prescription, and daily logs. Outcomes were measured at baseline
      and 2 months as part of a 1-year longitudinal randomized clinical trial. Outcomes
      included dyspnea during laboratory exercise and with activities of daily living
      (Chronic Respiratory Questionnaire [CRQ]), Shortness of Breath Questionnaire,
      Baseline/Transitional Dyspnea Index), exercise performance (incremental treadmill
      tests (ITTs) and endurance treadmill tests (ETTs), 6-minute walk (6MW), and
      health-related quality of life (SF-36). RESULTS: The DM-training group had
      significantly greater improvements than the DM-exposure and the DM groups in
      dyspnea at isotime during ITT (P =.006); exercise performance during ITT (P
      =.005), ETT (P =.003), and 6MW (P =.01); SF-36 Vitality (P =.031); and CRQ
      mastery (P =.007). There was a dose-dependent improvement in CRQ dyspnea scores
      (P <.05) with significant improvements only in the DM-training and DM-exposure
      groups. CONCLUSION: Exercise training substantially improved the impact of a
      dyspnea self-management program with a home walking prescription (DM). This
      impact tended to be dependent on the "dose" of exercise.

PMID- 11984210
TI  - Pulmonary rehabilitation after near-fatal asthma in an adolescent female.

PMID- 11984211
TI  - Helicobacter pylori infection, the cytotoxin gene A strain, and carotid artery
      intima-media thickness.
AB  - BACKGROUND: Chronic Helicobacter pylori infection has been implicated as a risk
      factor for stroke and other cardiovascular disease. It has been suggested that it
      acts by promoting atherogenesis. A particular strain of H. pylori, the cytotoxin
      gene A strain (CagA strain), which has been associated with increased
      inflammation, has been reported to account for much of this relationship. An
      early estimate of atherosclerosis can be obtained by ultrasonic imaging of the
      carotid artery to determine intima-media thickness (IMT). We determined whether
      H. pylori infection, and particularly the CagA strain, is associated with
      increased IMT. METHODS: In 983 normal population individuals we measured common
      carotid artery (CCA) IMT. From serum samples we determined H. pylori and CagA
      status. RESULTS: There was no significant association between H. pylori
      seropositivity and CCA IMT after controlling for age and gender. There were
      significant relationships between H. pylori seropositivity and a number of
      conventional cardiovascular risk factors (age, systolic and diastolic blood
      pressure, body mass index, smoking) and after controlling for these the magnitude
      of the regression coefficient was reduced by a further half. Amongst H. pylori
      seropositives the CagA strain was associated with increased IMT after controlling
      for age and gender (B = 0.0256, 95% CI 0.001-0.050, P = 0.038). The relationship
      was no longer significant after controlling for other cardiovascular risk
      factors. (B = 0.0194, 95% CI -0.004-0.042, P = 0.098). CONCLUSIONS: H. pylori and
      the CagA strain are not major risk factors for early arteriosclerosis as assessed
      by carotid artery intima-media thickness.

PMID- 11984212
TI  - Angiographic intervention trial using HMG CoA reductase inhibitor to evaluate
      retardation of obstructive multiple atheroma in West Japan (ATHEROMA study):
      rationale, design and baseline.
AB  - The ATHEROMA study is a prospective, multicentre, randomized controlled study in
      Japan to assess the changes of coronary atherosclerosis of patients with pre
      existing coronary artery disease (CAD) by cholesterol-lowering therapy (CLT)
      using pravastatin 10-20 mg per day for 3 years. The primary objective is to
      evaluate the changes in coronary minimum lumen diameters by quantitative coronary
      arteriography, and the secondary outcome is to observe morphological changes of
      plaques and clinical events including mortality, recurrence of CAD and the
      requirement of any coronary intervention. The primary objective will test the
      hypothesis that CLT results in a beneficial effect on coronary vessels in
      patients with coronary atherosclerosis in Japan, where the incidence of CAD is
      the lowest among industrialized countries. A total of 373 eligible patients were
      recruited from 799 patients and allocated to a dietary (n=187) and pravastatin
      regimen (n=186) by the minimization method. Clinical characteristics in the two
      groups were well matched and there were no differences in serum lipids and
      coronary status between them. The average +/- SD (range) of total, LDL and HDL
      cholesterol were 225.6 +/- 17.3 mg/dl, 141.9 +/- 21.2 mg/dl and 49.4 +/- 12.0
      mg/dl, respectively. Three years of follow-up were completed in late 2000, and
      cine angiograms blinded through the study coordinating centre were interpreted at
      the angiographic core laboratory. The final results, which are due to be
      published in 2002, will reveal whether or not specifically designed prophylactic
      strategy based on different cultural background is required.

PMID- 11984213
TI  - Current status of coronary risk factors among rural Malays in Malaysia.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of death in
      Malaysia, despite its status as a developing country. The rural population is
      thought to be at low risk. OBJECTIVE: To investigate the prevalence of risk
      factors and global risk profile among rural Malays in Malaysia. METHODS: We
      studied 609 rural Malay subjects (346 females, 263 males; age range 30-65 years).
      Blood pressure (BP), body mass index (BMI), waist-hip ratio (WHR), smoking habits
      and family history of premature CHD were documented. Fasting blood samples were
      analysed for serum lipids, lipoprotein (a), plasma glucose and fibrinogen. Oral
      glucose tolerance tests were performed using 75 g anhydrous glucose. RESULTS: The
      prevalence of hypercholesterolaemia for total cholesterol concentrations of > or
      = 5.2, > or =6.5 and > or =7.8 mmol/l were 67.3, 30.5 and 11.8% respectively.
      There was a high prevalence of low serum high-density lipoprotein cholesterol
      (13.1%), hypertension (30.3%), smokers (24.4%), diabetes (6.4%), impaired fasting
      glucose or glucose tolerance (13.9%), overweight or obesity (44.7%) and increased
      WHR (48.5%). Global risk assessment showed that 67.3% of the study population
      were at risk, with 15.9, 18.9 and 32.5% in the mild, moderate and high risk
      categories respectively. CONCLUSION: Prevalence of risk factors was high in the
      rural population. Global risk assessment showed a high-risk profile with two
      thirds being at risk, and one-third being categorized into the high-risk group.
      Although rural communities were considered at low risk of developing CHD, this is
      changing fast, possibly due to the rapid socio-economic development, in addition
      to underlying genetic predisposition.

PMID- 11984214
TI  - Glutathione S-transferase mu1 deficiency, cigarette smoking and coronary artery
      disease.
AB  - BACKGROUND: While genetic variation accounts for a large proportion of
      interindividual differences in coronary artery disease (CAD) development,
      environmental factors such as cigarette smoking may genotype-dependently initiate
      or accelerate the risk. Glutathione S-transferase mu1 (GSTM1) is one of the GST
      isoenzymes and contributes to the detoxification process of organic compounds
      produced by cigarette smoking. In the present study we explored the hypothesis
      that GSTM1 deficiency, caused by GSTM1 null allele, may predispose subjects to
      cigarette smoking related CAD risk. DESIGN: Cross-sectional. METHODS: We
      genotyped the GSTM1 null allele in 868 angiographically characterized CAD
      patients who were consecutively recruited in the present study. RESULTS: The
      frequency of the null genotype in this high-risk patient population was 57.1%
      (55.4% for males and 61.0% for females). While 75.7% male and 50.7% female null
      GSTM1 patients had significant CAD as defined by one or more significantly
      stenosed coronary arteries, 79.3% male and 48.3% female patients with positive
      GSTM1 also had the significant CAD (P > 0.05). However, although 54.3% male and
      55.2% female GSTM1 null patients had triple vessel disease, only 45.7% male and
      44.5% female GSTM1 positive patients had the severe disease. Controlling for
      cigarette smoking did not change the relationship. The occurrences of MI were
      37.9% in male and 31.4% in female with the null genotype whereas they were 42.8%
      in male 37.6% in female with positive GSTM1 (P > 0.05). Using logistic regression
      analyses, we found no interactions between GSTM1 genotype and cigarette smoking
      in relation to CAD or MI. CONCLUSIONS: While our data may be consistent with that
      the GSTM1 null genotype predisposes subjects to cigarette smoking related severe
      CAD, interactive effect on CAD risk is minor and insignificant. GSTM1 deficiency
      alone is not sufficient to cause CAD.

PMID- 11984215
TI  - Atorvastatin versus four statin-fibrate combinations in patients with familial
      combined hyperlipidaemia.
AB  - BACKGROUND: Statin-fibrate combinations are very effective in the treatment of
      familial combined hyperlipidaemia (FCHL). Nonetheless, they have not been
      extensively used because of the fear of side effects. Thus, a therapeutic
      alternative is required for this lipid disorder. OBJECTIVE: To compare the long
      term (one-year) efficacy of atorvastatin monotherapy with those of four statin
      fibrate combinations in 675 FCHL patients. METHODS: Patients were randomly
      assigned to atorvastatin monotherapy (A 20 mg/day) n = 134, or pravastatin (P 20
      mg/day)+gemfibrozil (G 1200 mg/day) n = 135, simvastatin (S 20 mg/day)+G (1200
      mg/day) n = 137, P (20 mg/day)+ciprofibrate (C 100 mg/day) n = 135, and S (20
      mg/day)+C (100 mg/day) n = 134. RESULTS: Twelve patients on statin-fibrate
      combinations were withdrawn from the study because of side effects: three because
      of CK elevation, two because of myalgia and seven due to increase in serum
      transaminase levels. One patient on A was withdrawn because of persistent
      epigastric discomfort. Atorvastatin reduced low density lipoprotein cholesterol
      and apoprotein B more than all four combinations (-45% vs. maximum -40% of S+C,
      and -39% vs. maximum -32% of the same combination, respectively, P < 0.001 for
      both), but had a lesser effect on triglycerides (-38% vs. maximum -53% of S+C, P
      = 0.0002) and high density lipoprotein cholesterol (6% vs. maximum 21% of S+G, P
      = 0.0003). The effect of A on plasma fibrinogen was analogous to that of G
      combinations (-8% vs. -9% of P+G and -11% of S+G, P = NS vs. baseline and among
      each other) and inferior to that of the ciprofibrate combinations (-8% vs. -24%
      of P+C, P = 0.0002 and -26% S+C, P = 0.0001). A had a lower treatment cost and
      better patient compliance, P = 0.04 vs. C combinations and P = 0.02 vs. G
      combinations. CONCLUSIONS: The data suggest that statin-fibrate combinations have
      a beneficial effect on all lipid parameters. Atorvastatin monotherapy has a
      better effect on LDL-C and apoprotein B than statin-fibrate combinations, but a
      lesser effect on HDL-C, TG and in the case of ciprofibrate combinations,
      fibrinogen. The clinical significance of these findings should be tested in a
      large, long-term survival study.

PMID- 11984216
TI  - The big mush: psychometric measures are confounded and non-independent in their
      association with age at initial diagnosis of Ischaemic Coronary Heart Disease.
AB  - The present study uses early diagnosis of ischaemic coronary heart disease (ICHD)
      as a proxy for disease malignancy in testing the statistical strength of
      association, and uniqueness/confounding, of several psychometric scales that have
      previously been found to prospectively predict death in cardiac samples (Beck
      Depression Inventory, Crown-Crisp Phobic Anxiety Scale, Type D Scale & Ketterer
      Stress Symptom Frequency Checklist). Eighty-three patients (no. of females = 35)
      with documented ICHD were assessed for traditional and psychometric risk factors.
      The psychometric risk factors were moderately to strongly intercorrelated, and
      strongly confounded in their relationship to age at initial diagnosis. In a
      stepwise multiple regression, only the AIAI (aggravation, irritation, anger and
      impatience) scale of the Ketterer Stress Symptom Frequency Checklist (KSSFC)
      survived as a predictor of age at initial diagnosis (P = 0.016). In a subgroup of
      the sample for whom the Spouse/Friend Version of the KSSFC was received (n = 58,
      or 70%), spouse/friend reported AIAI survived as the only predictor (P = 0.010).
      While present results need replication in a prospective study of diagnosed ICHD
      patients for all important clinical outcomes, only one psychometric screening
      instrument may be necessary to identify patients in need of treatment.

PMID- 11984217
TI  - Wives of patients with acute myocardial infarction are at an increased risk of
      developing coronary artery disease.
AB  - BACKGROUND: The present study was carried out to investigate risk factors for
      developing coronary artery disease in wives of patients with acute myocardial
      infarction. SUBJECTS AND METHODS: Risk factors for developing coronary artery
      disease were investigated in 50 wives of patients who developed an acute
      myocardial infarction (group A) and were compared with those of 50 wives of
      normal healthy men (group B). The average age was 50.20 +/- 1.56 years (mean +/-
      SD) and 50.20 +/- 1.53 years for group A and group B respectively. The parameters
      assessed were: plasma cholesterol (TC), high density lipoprotein cholesterol (HDL
      C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic and
      diastolic blood pressure, smoking habits and body mass index (BMI). RESULTS: The
      levels of LDL-C in the wives of patients with myocardial infarction were higher
      than those of the wives of normal healthy men (167.8 +/- 5.84 mg/dl and 148.4 +/-
      4.85 mg/dl, respectively, P < 0.01). Moreover, HDL-C concentrations were lower in
      the wives of the patients (51.34 +/- 0.92 mg/dl) than in the wives of the healthy
      men (58.14 +/- 1.39 mg/dl), (P < 0.001). Finally, TG levels were higher in the
      wives of the patients (132.2 +/- 7.9 mg/dl) than in the wives of the normal
      healthy men (96.9 +/- 5.94 mg/dl) (P < 0.01). CONCLUSIONS: Although plasma lipid
      levels themselves were not excessively high, the wives of patients with an acute
      myocardial infarction are at a higher risk of developing coronary artery disease
      than the wives of normal healthy men, in the long term, due to higher levels of
      LDL-C and TG as well as lower levels of HDL-C.

PMID- 11984218
TI  - Endothelium-dependent vasodilation is impaired in apparently healthy subjects
      with a family history of myocardial infarction.
AB  - OBJECTIVES: To investigate whether endothelial-dependent vasodilation is altered
      in healthy subjects with a family history of myocardial infarction. SETTING:
      Tertiary University Hospital SUBJECTS AND DESIGN: Fifty apparently healthy
      subjects selected from the general population were subjected to an evaluation of
      endothelial-dependent vasodilation (EDV) and endothelial-independent vasodilation
      (EIDV) by means of local infusion of methacholine (MCh, 2 and 4 microg/min) and
      sodium nitroprusside (SNP, 5 and 10 microg/min) with measurements of forearm
      blood flow with venous occlusion plethysmography. The occurrence of plaque and
      the intima-media thickness of the carotid arteries were determined by
      ultrasonography. RESULTS: Subjects reporting at least one parent suffering from
      myocardial infarction (n = 11) showed a significantly lower EDV than subjects
      without such a family history (21 +/- 3.7 vs. 26 +/- 6.7 ml/min/100 ml tissue at
      MCh 4 microg/min, P<0.05). EIDV was not significantly different between the
      groups (21 +/- 6.8 vs. 18 +/- 5.4 ml/min/100 ml tissue at SNP 10 microg/min).
      Age, sex distribution, body mass index, waist to hip ratio, blood pressure,
      lipids, fasting blood glucose, smoking habits and status of the carotid arteries
      were not significantly different between the groups. CONCLUSION: A family history
      of myocardial infarction was found to be associated with an impaired endothelial
      dependent vasodilation in the forearm of apparently healthy subjects. The risk
      factor profile was not different from the control group, suggesting that genetic
      factors are responsible for the impaired endothelial-dependent vasodilation.

PMID- 11984219
TI  - The poliovirus receptor related 2 (PRR2) and apolipoprotein E genes and coronary
      heart disease.
AB  - BACKGROUND: Recently, we localized the Human Poliovirus Receptor Related 2 Gene
      (PRR2) 17kb centromeric to the gene for apolipoprotein E (APOE). Common
      polymorphisms in the latter have been found, in some studies, to be related to
      coronary heart disease (CHD) but the PRR2 gene has not been studied in this
      context. Here, we examined relationships between a PRR2 Sau96I (A/G)
      polymorphism, the epsilon2, 3 and 4 alleles of APOE and CHD. DESIGN AND METHODS:
      Consecutive Caucasian patients (n = 640) < 50 years with angiographically
      documented coronary obstructive disease and/or with unequivocal myocardial
      infarction were compared with 624 control subjects, aged 30-50 years, randomly
      selected from the community and without a history of CHD. RESULTS: An excess of
      PRR2-A homozygotes was observed in cases (20% vs. 15%; OR 1.4, CI 1.04-1.86, P =
      0.026) particularly in those with single vessel disease (OR 1.7, CI 1.2-2.4, P
      <0.01). The A allele was in linkage disequilibrium with the epsilon4 allele and
      the G allele with the epsilon2. Overrepresentation of the A allele and
      underrepresentation of the G allele in the CHD group did not reach significance
      (P = 0.054). While the epsilon2 allele was underrepresented in the CHD group (OR
      0.64, CI 0.46-0.89, P = 0.009), the epsilon4 allele was not significantly
      overrepresented. CONCLUSION: The relationship between the PRR2 Sau96I (A/G)
      polymorphism and early onset coronary artery disease may be due to linkage
      disequilibrium with the APOE gene and underrepresentation, or a protective
      effect, of the epsilon2 allele. Alternatively, since A allele homozygosity is
      particularly overrepresented, the relationship could be more direct, perhaps
      through a viral association.

PMID- 11984221
TI  - Infusion nurses society position paper. Administration of antineoplastic agents.
AB  - The Infusion Nurses Society (INS) recognizes the inherent risks to the patient,
      caregiver, and healthcare professional associated with the administration of
      antineoplastic agents. Individuals involved in the administration of these agents
      should have documented specialty education and demonstration and documentation of
      competency on a regular basis according to organizational policies and
      procedures.

PMID- 11984222
TI  - Test your knowledge: preparing to take the CRNI exam. Pediatrics.
AB  - The CRNI Certification Examination consists of 200 multiple-choice questions
      covering the nine core content areas of infusion nursing: Technology and Clinical
      Applications, Fluid and Electrolyte Balance, Pharmacology, Infection Control,
      Pediatrics, Transfusion Therapy, Antineoplastic Therapy, Parenteral Nutrition,
      and Quality Assurance. The review questions provided below are modeled on the
      CRNI exam and are intended to help exam candidates test their knowledge of
      infusion therapy practice. This special section is a regular addition to the
      Journal of Infusion Nursing, with each edition focusing on a single content area.

PMID- 11984223
TI  - Reducing infusion phlebitis in Singapore hospitals using extended life end-line
      filters.
AB  - Two studies were conducted to investigate the impact of the 4-day end-line filter
      used to treat infusion phlebitis in Singapore. In the first study, conducted in
      1997, 200 patients received IV antibiotics and chemotherapy. In the first 100
      patients, end-line filters were not used during the infusions. This resulted in a
      phlebitis rate of 31%. In the second group of 100 patients, end-line filtration
      was used, resulting in a phlebitis rate of 5%. In 2000, a second study was
      conducted, measuring the outcome of end-line filtration versus no end-line
      filtration use. In this case, phlebitis developed in 35% of 100 patients
      receiving antibiotics, as compared with 8% of 394 patients with the use of 4-day
      end-line filtration. These are the first such studies performed in Southeast Asia
      that highlight identical benefits, namely the reduction of phlebitis by
      elimination of particulates, in two separate patient populations. End-line
      filtration, when used to deliver antibiotics and chemotherapy, will result in
      significantly fewer cases of infusion phlebitis, reduce the cost of delivering IV
      antibiotics and chemotherapy, increase nursing efficiency, and ultimately improve
      patient comfort.

PMID- 11984224
TI  - Methods for treating diabetic gastroparesis.
AB  - Diabetic gastroparesis, caused by an autonomic neuropathy of the vagus nerve, is
      seen in up to 50% of individuals with diabetes. It results in a delay of gastric
      emptying that wreaks havoc on glycemic control and also has nutritional
      implications. Treatment is directed toward ameliorating symptoms and improving
      nutritional and glycemic control.

PMID- 11984225
TI  - Comparing the effect of a skills checklist on teaching time required to achieve
      independence in administration of infusion medication.
AB  - This study evaluated the efficacy of a skills checklist, which included a
      standardized instruction sheet based in part on Rutledge and Donaldson's
      recommendations for reducing the amount of time required to make a patient
      independent in the administration of an antibiotic. The use of a skills checklist
      was found to reduce the time it takes for a patient to become independent with
      their therapy by reducing the number of teaching visits, and thereby the total
      time of instruction. Time-saving and a decrease in the number of individuals
      providing instruction to a patient offer the prospect of lowering the cost of
      care. The skills checklist also improves communication between nurses providing
      instruction.

PMID- 11984226
TI  - Reflex sympathetic dystrophy syndrome.
AB  - Reflex sympathetic dystrophy is a condition characterized by unrelenting pain,
      swelling, discoloration, temperature, and physical changes in the affected body
      part that are life-altering for the patient and the family. Early diagnosis and
      treatment are essential to minimize the progressive disability from this disorder
      that results in limb pain, physical changes, and deformity. This article
      considers the current understanding of RSDS in terms of historical perspective,
      clinical features, pathophysiologic theories, diagnostic evaluation, treatment
      options, and nursing care.

PMID- 11984227
TI  - Use of hepatic lines: their journey from percutaneous to implantable.
AB  - Hepatic arterial infusions have been performed since the early 1980s, primarily
      for the treatment of hepatocellular cancer, but also for metastatic (hepatic)
      colorectal carcinoma. The goal is to infuse chemotherapy directly into the
      hepatic artery, thereby providing high concentration of the drug to the tumor
      while limiting systemic side effects. This article explores the evolution of
      hepatic arterial catheters and delivery systems over the past 20 years. Anatomy
      and physiology is briefly reviewed and the history of hepatic catheters is
      presented along with their placement, care, and complications.

PMID- 11984228
TI  - Becoming a nurse-writer: advice on writing for professional publication.
AB  - Successful nursing professionals already have what it takes to write for
      publication, namely, strong oral and written communication skills honed every day
      in the workplace. Nurses spend much time and effort in training and actual
      practice refining their rhetorical skills, that is, their ability to communicate
      ideas clearly and persuasively to a variety of audiences composed of physicians,
      other nursing professionals, pharmaceutical representatives, patients, and their
      families. Without a doubt, experienced nurses have what it takes to write for
      professional publication.

PMID- 11984229
TI  - Their money or your health: who owns health care?

PMID- 11984230
TI  - Seven methods to effectively manage patient care labor resources.

PMID- 11984231
TI  - Thoughts on nursing work.

PMID- 11984232
TI  - Performance management data systems for nursing service organizations.
AB  - Increasing demands are being placed on nursing administrators to manage the cost
      efficiency and quality-effectiveness of the nursing service organization. One
      effective administrative tool that can be used for both internal management and
      external reporting of a nursing service organization performance is the
      performance management data system described in this article. While efforts are
      underway to build essential elements of a performance management data system,
      including the structure and content of nursing-sensitive databases and data
      management methods, no consensus has been reached. The author reviews the
      relevant literature and offers guidelines to take the nursing administrator
      through the process of developing a performance management data system. Beginning
      with a conceptualization of the nursing service organization as a system, the 5
      phased process moves through data variable selection, data variable measurement,
      and data analysis to the final internal and external reporting of the
      organization's performance.

PMID- 11984233
TI  - The nursing shortage. Past, present, and future.
AB  - According to healthcare experts, the present nursing shortage is going to extend
      to 2020 with an estimated 400,000 RN vacancies. A number of factors are
      contributing to the shortage: an increase in the age of registered nurses,
      decreased school enrollment, increased career opportunities for women, changes in
      the healthcare delivery system, nurse "burn-out," and the public's
      misunderstanding of what nurses do. Additionally, a number of social and economic
      trends are going to affect the healthcare delivery system in the future, such as:
      aging of the population, increased technology, the increase of the
      health/wellness movement, changes in employee's work ethic, influence of
      Generation X and dot.com workers, and scarcity of entry-level and low-wage
      workers. If nursing is going to be a major player in the healthcare delivery
      system in 2020, nurses must take an active role in developing and implementing a
      strategic plan. We need to look beyond solutions used in the past, such as
      increasing compensation and modifying school curriculums.

PMID- 11984234
TI  - Evidence-based nursing practice, Part 2: Building skills through research
      roundtables.
AB  - Numerous articles describe barriers to nurses conducting research and achieving
      evidence-based practice as well as strategies for overcoming barriers. The
      Research Roundtable format is one such strategy. It is an interactive means for
      providing novice nurse researchers and nursing students with the skill sets
      required to drive application of existing evidence to nursing practice and
      conduct outcome studies to derive new evidence. The authors discuss their
      Research Roundtable series that addressed a number of barriers to research,
      research utilization, and evidence-based practice and how the series increased
      nurses knowledge and skills, demystified the research process, provided role
      models, demonstrated managerial and collegial support, and provided library,
      fiscal, and other resource support to complete staff projects. The details of the
      Research Roundtable series will guide others in replicating the process in their
      own organizations and academic communities.

PMID- 11984235
TI  - Professional staff education. Quantifying costs and outcomes.
AB  - In today's cost-conscious marketplace, it is critical to identify the true costs
      of professional staff development within a healthcare organization. Many hidden
      costs can be difficult to quantify. This article will help administrators
      identify these costs, and decide whether their professional staff education would
      be done better internally or using outside resources.

PMID- 11984236
TI  - Is shared governance still relevant?

PMID- 11984237
TI  - Nursing quality outcome indicators. The North Dakota Study.
AB  - The purpose of this study was to assess the feasibility and conduct a pilot study
      of the ANA Nursing Care Report Card Study in one state. Clinical indicators
      studied include agency data, skin integrity, patient falls, and nurse (n = 217)
      and patient (n = 924) satisfaction. Patients were well satisfied with their care.
      Nurses were less satisfied, with a significant difference between what was
      important to their satisfaction and their current level of satisfaction.
      Important information is included for hospital and nursing service
      administrators, as well as for nurses.

PMID- 11984238
TI  - Communication. Improving RNs' organizational and professional identification in
      managed care hospitals.
AB  - Nurse administrators are searching for an expanded repertoire of strategies to
      attract and retain qualified nursing staff in today's managed care environment.
      This study examined hospital registered nurses' interpretations of managed care
      and the effects of those views on nurses' identification with their employing
      organization and the nursing profession. Findings show that nurses held greater
      identification with their occupation than their organization. Significant factors
      influencing nurses' attachment to both of these reference groups included
      uncertainty about managed care changes, information received about managed care
      changes, and effects of managed care on the nursing role. Communication
      principles and strategies are presented to nurse leaders for use in fostering a
      stronger organizational affiliation among staff nurses while maintaining a strong
      identification with the nursing profession.

PMID- 11984239
TI  - Inspiring support staff employees.

PMID- 11984240
TI  - Tough times in healthcare.

PMID- 11984241
TI  - Advanced practice nursing. Acute care model in progress.

PMID- 11984242
TI  - From executive to retiree.

PMID- 11984243
TI  - Retaining rural and remote area nurses. The Queensland, Australia experience.
AB  - Because higher-than-average turnover rates for nurses who work in remote and
      rural areas are the norm, the authors conducted a study to identify professional
      and personal factors that influenced rural nurses' decisions to resign. Using a
      mail survey, the authors gathered qualitative and quantitative data from nurses
      who had resigned from rural and remote areas in Queensland, Australia. Their
      findings, categorized into professional and rural influences, highlight the
      importance of work force planning strategies that capitalize on the positive
      aspects of rural and remote area practice, to retain nurses in nonmetropolitan
      areas.

PMID- 11984244
TI  - Nursing manager leadership skills.
AB  - Nurse managers are internal stakeholders who play essential roles in managing
      change, cultural integration, retention, and direction of staff attitudes toward
      changing healthcare structures. The challenges facing them as they attempt to
      understand and to support employees during times of change are monumental. They
      frequently assume expanded roles and responsibilities without adequate education,
      resources, or support. The author reports variables key to the success of the
      role and areas of education that may influence that success.

PMID- 11984245
TI  - Registered nurse unions and patient outcomes.
AB  - Although research shows substantial relationships between several organizational
      characteristics in hospitals and patient outcomes, the relationship between nurse
      unions and patient outcomes has not been explored. Because of the workplace chaos
      of the last half of the 1990s, some nurses are rethinking their relationships
      with unions; some have the perception that union activity has increased. It is
      not always clear whether changes in healthcare are associated with patient
      outcomes, but it is clear that hospitals/health systems with unions often engage
      in spirited rhetoric about what is best for patients with little objective
      evidence to support either view. This study examines the relationship between the
      presence of a bargaining unit for registered nurses and the acute myocardial
      infarction mortality rate for acute care hospitals in California. The authors
      also discuss how registered nurse wage, hospital bed size, volume of patients,
      and other organizational factors may influence and confound this relationship.

PMID- 11984246
TI  - Job strain among staff of rural nursing homes. A comparison of nurses, aides, and
      activity workers.
AB  - Caring for growing numbers of residents with Alzheimer's disease and related
      dementias increases the potential for stress among nursing home staff. To better
      understand occupational stress among caregivers in rural nursing homes, the
      authors studied differences in job strain among registered nurses, nursing aides,
      and activity workers. The authors discuss data from their survey questionnaires
      and focus group interviews with staff, providing insight into job strain and
      possible intervention strategies to improve the work environment.

PMID- 11984247
TI  - The nursing shortage. Implications for military nurses.
AB  - Trends relative to nursing vacancies are expected to exist into the next decade.
      Unlike the cyclical shortages of the past, this shortage may not resolve itself.
      The authors present five major factors in nursing that have led to the shortage
      and that contribute to its continuation. Because military nurses provide much
      manpower in the healthcare industry, shortages in their ranks will affect the
      entire healthcare system. The five factors were applied to the military nursing
      force to demonstrate that the military also feels the pinch of the current
      nursing shortage.

PMID- 11984248
TI  - Regionalization: economies of scale for acute critical care.

PMID- 11984249
TI  - Filipino nurse recruitment as a staffing strategy.
AB  - Challenging times require challenging strategies. The recruitment of nurses from
      the Philippines is a strategy that makes sense both ethically and economically
      when the processes are managed by well-capitalized vendors with experience and
      expertise in the area. A one-stop turnkey approach for a set fee is recommended.
      Filipino nurse recruitment addresses short-term and intermediate-term strategies
      that can offer support to hospitals and full-time employed nurses needing more
      help to do their work. This process benefits the patient who needs access to
      care, it benefits the employing organization as an economical method to fill
      vacant positions, it benefits the Filipino nurse who has an opportunity for a
      better quality of life than she would have access to in her homeland, the
      colleagues on the rest of the clinical team are benefited by having qualified
      staff to share the workload, and the home country of the Filipino nurse benefits
      when the expatriate nurses send money regularly that goes back into the general
      economy of the country.

PMID- 11984250
TI  - Saving nursing management.

PMID- 11984251
TI  - When you have to leave. Readjusting attitude.

PMID- 11984252
TI  - Strategic partnerships.

PMID- 11984253
TI  - Where have all the nursing administration students gone? Issues and solutions.

PMID- 11984254
TI  - Realizing your marketing influence, Part 1. Meeting patient needs through
      collaboration.
AB  - To what degree do or should marketing and nursing overlap? If marketing is about
      meeting patient needs, who better than the nursing staff to inform marketing
      decisions? Meeting patient needs profitably ensures that patient care can
      continue to move toward excellence. As competition continues to intensify and
      reimbursement remains insufficient, using all of the healthcare system's
      available intellectual capital is imperative to achieving maximum competitive
      advantage. The author applies current marketing theory to the healthcare
      environment and provides practical suggestions on how nursing administrators and
      staff can work collaboratively with marketing colleagues to develop and implement
      strategic marketing programs. This is the first in a series of 3 articles, which
      will move readers from broad marketing strategy to specific applications. The
      second (June, 2002) and third articles (July/August, 2002) will focus on internal
      marketing and using professional certification as a marketing tool.

PMID- 11984255
TI  - Critical pathways. A systematic review.
AB  - Critical pathways are care plans that detail the essential steps in patient care
      with a view to describing the expected progress of the patient. The authors'
      review of the literature suggest the use of critical pathways reduces the cost of
      care and the length of patient stay in hospital. They also have a positive impact
      on outcomes, such as increased quality of care and patient satisfaction, improved
      continuity of information, and patient education.

PMID- 11984256
TI  - Exploring emotional intelligence. Implications for nursing leaders.
AB  - Emotional intelligence is being touted in the popular literature as an important
      characteristic for successful leaders. However, caution needs to be exercised
      regarding the connection between emotional intelligence and workplace success.
      The author contrasts 2 current models of emotional intelligence, the measurements
      being used, and the ability of emotional intelligence to predict success.
      Implications for the workplace are discussed.

PMID- 11984257
TI  - New graduate RNs in a float pool. An inner-city hospital experience.
AB  - Nurse managers and nurse educators alike have historically discouraged hiring new
      graduate RNs into a float pool and have preferred experienced nurses with
      multiple clinical skills. With a nursing shortage and changing marketplace, we
      need different strategies for recruitment and retention and ways to improve our
      clinical practice. A new graduate RN offers a nursing service an opportunity to
      employ a motivated, ready-to-learn, educationally prepared and intellectually
      stimulated nurse who happens to have limited clinical experience. The authors
      present a program for training new graduate RNs to practice nursing in a float
      pool. The training program focuses on their clinical practice needs and on
      transitioning them to the RN role. This program resulted in a 96% retention rate.
      The program offered our medical surgical units a strong clinical support float
      nurse, our managers a staffing solution in times of need, and the new graduate RN
      a broad range of clinical experiences making them more valuable members of the
      healthcare team. This training model is one approach to increasing recruitment
      and retention and can be replicated in other institutions.

PMID- 11984258
TI  - CAM therapies and nursing competency.
AB  - Americans are embracing complementary and alternative medical (CAM) therapies in
      ever-increasing numbers, with more than $30 billion spent on CAM each year. This
      consumer-driven trend challenges staff development leaders to learn more about
      CAM and the implications for staff competency. This article reviews CAM
      integration from the Federal to state level, and describes guidelines to
      facilitate development of policies related to CAM, nursing competency, and
      promotion of patient advocacy in use of CAM therapies.

PMID- 11984259
TI  - Principles of web site development and design: powerful educational tools.
AB  - Setting up an educational Web site is easy and is a huge benefit to the nursing
      profession. Although Web sites may radically differ in their audiences and
      intent, the principles behind a great site are the same. This article provides
      basic information, terminology, and advice on how to create effective Web sites
      using concepts of Web design and Web publishing.

PMID- 11984260
TI  - Supporting preceptors.
AB  - For effective teaching of nursing students and management of stress of increased
      workloads, preceptors require a great deal of support from nursing faculty,
      peers, and administrative personnel. Through a mailed survey, 295 preceptors
      reported that they would have appreciated more support. The best support is the
      continued and visible presence and involvement of instructors, which can be
      provided in person, by telephone, or via fax. This is best achieved if nurse
      educators, directors, and deans view themselves as copreceptors.

PMID- 11984261
TI  - How to facilitate the orientation of new nurses into the workplace.
AB  - The orientation of new nursing graduates into the workplace is an impressive
      challenge. A research study was performed to identify the key elements of a
      program that would address the various issues regarding this orientation. A team
      of researchers from Laval University and the Centre Hospitalier Universitaire de
      Quebec (CHUQ) used a descriptive and participative research method and identified
      five key elements that must be considered in order for this orientation to
      succeed.

PMID- 11984262
TI  - Designing and implementing an RN refresher course for the acute care hospital:
      development of the nurses' critical thinking skills.
AB  - With today's nursing shortage, hospitals are seeking creative strategies to
      recruit nurses. The task of recruiting inactive nurses has been more difficult
      because of the challenges faced by hospital-based nurses in this era of managed
      care and increased acuity of patients. This article describes a unique 8-week
      course, which provides the nurses with an update of technical skills and
      emphasizes the development of the critical-thinking skills necessary to deliver
      safe, competent patient care.

PMID- 11984263
TI  - Development of educator competencies and the professional review process.
AB  - As staff development educators prepare themselves and their organizations for
      forthcoming healthcare challenges, educators influence the practice of staff
      development through the use of competencies. Because competencies and peer review
      are expectations for staff, educator competencies and educator professional
      review should be essential for those who train staff. Based upon the American
      Nurses Association Standards of Practice, National Nursing Staff Development
      Organization research, and Patricia Benner's work, competencies for educators
      reflect practice levels from novice to expert and challenge educators to attain
      levels of excellence in practice. Use of educator competencies includes the
      professional review process components of peer input, self-evaluation, and
      portfolio development. Portfolio development provides documentation of educator
      accomplishments for the organization. This approach to educator competencies
      serves as a strategy to position educators to meet healthcare demands and
      demonstrates leadership in the profession. The staff development educators at a
      large Midwestern health system have refined this process during the past 2 years,
      and their unique approach to educator competencies and professional review can
      benefit both individual educators and healthcare organizations now and in the
      future.

PMID- 11984264
TI  - Policies and procedures: from binders to PCs: a retrospective.
AB  - This article describes the implementation of an online, document-tracking system
      for policies and procedures. The process of converting from a "binder system" to
      an online, paperless system is described in detail. The advantages of real-time
      computer access to staff are identified as well as the necessary steps needed to
      move an entire hospital into the future and use emerging technology.

PMID- 11984265
TI  - Instant teaching tools.

PMID- 11984267
TI  - Entrepreneurial case management.

PMID- 11984268
TI  - Rural case management: nursing role variations.
AB  - The authors describe a study of rural case managers' role perceptions. Although
      various studies have investigated the role of the case manager, no study has
      examined the role in a rural environment. Survey data and focus groups are used
      to determine information about the role. Nurses identified differences and
      problems associated with the case management role in the rural environment.
      Respondents in the study also identified changes in role expectations, essential
      clinical skills for rural case managers, and ways in which case management
      affects healthcare outcomes for rural clients. Essential elements of content for
      educational preparation of these case managers are also investigated.

PMID- 11984269
TI  - Don't squander case management resources.

PMID- 11984270
TI  - How to begin or add a geriatric care management business.

PMID- 11984271
TI  - Case management guideline: Alzheimer disease and other dementias.
AB  - Case management guidelines are an integration of information obtained from
      research, observations, clinical experience, and judgments of expert clinicians,
      scientists, and clients. This guideline integrates information from multiple
      practice guidelines in order to guide the case manager in managing clients with
      Alzheimer disease and other dementias. The guideline provides direction in
      recognition of symptoms or triggers, risk factors, possible complications, case
      management outcomes, barriers to effective outcomes, goals,
      providers/practitioners, treatment options, location of treatment, estimated cost
      of treatment, psychosocial issues, life planning and long-term planning,
      vocational issues and teaching protocols. In addition, resource contacts and
      sources for major instruments used in measuring Alzheimer disease and dementia
      are presented.

PMID- 11984272
TI  - Do you love nursing?

PMID- 11984273
TI  - Nurse tracking systems: do the benefits to nurse managers outweigh risks to
      nurses' privacy?

PMID- 11984275
TI  - Primary care of the premature infant discharged from the neonatal intensive care
      unit.
AB  - Premature infants require varying degrees of newborn intensive care and have a
      wide range of physical and developmental outcomes. Subsequent ambulatory care for
      these infants is often complex. Although tertiary hospitals often provide
      multidisciplinary follow-up clinics, the pediatric nurse practitioner (PNP)
      responsible for primary care has a unique opportunity to influence the lives of
      these special babies and their families. While the basic principles of well child
      care and health maintenance apply to this special population, there are several
      inherent challenges. The transition from neonatal intensive care unit (NICU) to
      home can be stressful for families. Infants born prematurely often have
      unpredictable behavior and present with cues that are vague and unclear to
      caregivers. Growth must be monitored adjusting for prematurity, and nutrition
      must be tailored to the physical and developmental level of the infant.
      Assessments of development, vision, and hearing must also be adjusted for
      prematurity. Fortunately, the majority of premature infants discharged from the
      NICU thrive and develop normally. However, some will experience medical problems
      and developmental delay. Knowledge of complications common to premature infants
      will be helpful to the PNP providing primary care. These include difficulties of
      growth and feeding, gastroesophageal reflux, apnea and bradycardia, chronic lung
      disease, fine and gross motor abnormalities, and other learning problems.
      Providing care to the NICU graduate is one of the challenges faced by PNPs in
      primary care, but one that is both rewarding and enjoyable.

PMID- 11984276
TI  - Neural tube defects.
AB  - The purpose of this article is to describe the etiology of neural tube defects
      (NTDs) and the role of folic acid in their prevention. NTDs are all too common
      and devastating outcomes of many pregnancies. The brain and spinal cord
      malformations that develop during gestation in the NTD-affected pregnancies are
      expressed through various anomalies. Estimates by the Centers for Disease Control
      and Prevention (CDC) for 1995 reported over 4,000 occurrences of NTDs in the
      United States alone. Research has demonstrated that the preconception and
      prenatal addition of folic acid can greatly reduce the incidence of NTDs. Recent
      advances in genetic studies have increased awareness of the important role of
      folic acid in preventing NTDs. Identification of a genetic marker will allow for
      specific treatment of those women at high risk for NTDs. Despite recommendations
      from the CDC for folic acid supplementation, there is insufficient awareness of
      these guidelines by both the public and by healthcare providers. A National
      campaign to promote awareness of the role of folic acid in the prevention of NTDs
      has been initiated, and has been successful at reducing NTDs's by 19%. Nurses can
      be instrumental in the dissemination of information not only to women of
      childbearing age, but also to other nurses and physicians.

PMID- 11984277
TI  - Autonomic dysreflexia.
AB  - The purpose of this article is to help perinatal nurses understand how to more
      effectively care for women in labor who have spinal cord injuries (SCIs),
      especially those women who develop the complication of autonomic dysreflexia
      (AD). AD is a syndrome that can occur in patients with SCIs above the level of
      T6. Its symptoms include dangerous paroxysmal hypertension, resulting from
      abnormal interplay between the parasympathetic and sympathetic nervous systems.
      While this syndrome was not commonly encountered by perinatal nurses in
      childbirth settings in the past, the dramatic improvements in both acute care and
      rehabilitation for women with SCI has increased the numbers of women with SCI who
      become pregnant and experience childbirth. Therefore, it is essential that
      perinatal nurses be made aware of how to effectively identify AD, and what steps
      to take should it occur.

PMID- 11984278
TI  - A descriptive study of women's perceptions of their asthma during pregnancy.
AB  - PURPOSE: To determine the impact of asthma during pregnancy from the perspective
      of the pregnant woman. STUDY DESIGN AND METHODS: A descriptive survey using the
      Internet for subject recruitment and data collection was conducted using an
      adaptation of the Cancer Survivors Survey Questionnaire. Women with asthma who
      were pregnant or who had recently given birth (n = 166) were the sample. Women
      responded from the United States, Canada, Europe, and Asia. Physical symptoms,
      emotional responses, and coping strategies to deal with the asthma were queried.
      RESULTS: Women reported a variety of respiratory difficulties including wheezing,
      coughing, and shortness of breath. They were concerned about avoiding triggers
      leading to acute asthma, the effect of the asthma medications on the fetus, and
      losing their jobs due to absenteeism. They wanted to know more about how to
      prevent an asthma attack and what effect their disease could have on their unborn
      infants. CLINICAL IMPLICATIONS: Women need education and support to help them
      deal with asthma during pregnancy. Nursing can have an important role in teaching
      these women and helping them monitor their asthma status during pregnancy.

PMID- 11984279
TI  - Who knows more about condoms? A comparison between nursing students, education
      students, and at-risk adolescents.
AB  - PURPOSE: To examine knowledge regarding appropriate use of condoms and lubricants
      among three groups: female at-risk adolescents, nursing students, and education
      students. METHODS: Study participants were 236 adolescents: 65 recruited through
      community agencies, 79 female nursing students, and 92 female education students.
      These participants completed anonymous questionnaires concerning lubricants,
      general condom knowledge, and sexual experience. RESULTS: Neither nursing
      students nor education students were more knowledgeable than adolescents not
      enrolled in college. All participants were about as likely to think unsafe
      lubricants were safe as they were to think that safe lubricants were unsafe.
      Personal experience with vaginal intercourse and condom use was associated with
      increased knowledge (p < 0.05). However, 27% to 66% of participants who had used
      condoms answered the lubricant questions incorrectly. IMPLICATIONS: Nursing
      students need more education about condoms and condom lubricants if they intend
      to teach patients effectively. Moreover, nurses should not assume that youth are
      knowledgeable about appropriate condom use based on their level of education or
      sexual experience.

PMID- 11984280
TI  - "Keep a blank face. I need to tell you what has been happening to me.
AB  - PURPOSE: To explore adolescents' experiences of abuse in the year before and
      during pregnancy. METHODS: This prospective study used structured and focused
      interviews and content analysis. Forty teens' stories of abuse were extracted
      from focused interview questions during a larger study of pregnant adolescents
      aged 18 to 20. Elements of the stories were coded and categorized according to
      content and meaning. Seven themes were identified using a generalized qualitative
      approach that blended content and thematic analysis. RESULTS: Teens reported
      abuse from a variety of individuals, including intimate partners, former
      partners, and family members. Thirteen of the 40 teens reported being pregnant in
      the year before the index pregnancy, with 11 of the pregnancies ending in
      miscarriage, elective abortion, or fetal demise. Four of the pregnancy losses
      were directly attributed to abuse. Seven themes were identified that reflected
      the teens' stories of violence: seeking safety (self-protection with risks and
      benefits); losing faith (negative experiences with police and social justice
      institutions); experiencing loss (compromised reproductive health); living on the
      edge (substance abuse concerns); taking the next step (developmental concerns);
      crying out for help (suicide attempts); and changing and temporary relationships
      (loss of family bonds and serial monogamy). CLINICAL IMPLICATIONS: Routine
      screening for violence prior to and during pregnancy should include questions
      about past pregnancies, sexual abuse, and multiple perpetrators, as well as
      perpetrators other than intimate partners. Adolescent developmental concerns
      should be incorporated in safety planning and advocacy interventions.

PMID- 11984281
TI  - Sterile speculum exams, nitrazine, and ferning.

PMID- 11984282
TI  - Are there legal issues of concern for nurses when patients use complimentary and
      alternative medicine?

PMID- 11984283
TI  - Nursing support during pregnancy.

PMID- 11984284
TI  - Gender as a qualification.

PMID- 11984285
TI  - Are you an empowered nurse?

PMID- 11984286
TI  - Public health nurses.

PMID- 11984287
TI  - Cardiorespiratory fitness and smoking-related and total cancer mortality in men.
AB  - PURPOSE: We investigated the association between cardiorespiratory fitness and
      smoking-related, nonsmoking-related, and total cancer mortality in men. METHODS:
      We followed 25,892 men, age 30-87 yr, who had a preventive medical evaluation,
      including a maximal exercise test and self-reported health habits. There were 335
      cancer deaths (133 from smoking-related cancer, 202 from nonsmoking-related
      cancer) during an average of 10 yr of follow-up (259,124 man-yr). RESULTS: After
      adjustment for age, examination year, smoking habits, alcohol intake, body mass
      index, and diabetes mellitus, there was an inverse association between
      cardiorespiratory fitness levels and smoking-related (P < 0.001 for trend),
      nonsmoking-related (P = 0.001 for trend), and total cancer mortality (P < 0.001
      for trend). Moderate and high levels of cardiorespiratory fitness were associated
      with lower risk of smoking-related and nonsmoking-related cancer mortality when
      compared with low fitness in men. We also observed that smoking-related mortality
      rates were progressively lower across low, moderate, and high fitness groups in
      former (P = 0.06 for trend) and current (P = 0.04 for trend) smokers. CONCLUSION:
      We conclude that cardiorespiratory fitness may provide protection against cancer
      mortality in men.

PMID- 11984288
TI  - Musculoskeletal fitness and risk of mortality.
AB  - PURPOSE: To quantify the relationship between musculoskeletal fitness and all
      cause mortality in the Canadian population. METHODS: The sample consisted of 8116
      people (3933 men and 4183 women), aged 20-69 yr, who participated in the 1981
      Canada Fitness Survey. Measures of musculoskeletal fitness included sit-ups, push
      ups, grip strength, and sit-and-reach trunk flexibility. In the 13 yr after the
      Canada Fitness Survey, there were 238 deaths and a total of 101,685 person-years.
      Proportional hazards regression was used to estimate the risk of mortality across
      baseline age- and sex-specific quartiles of the musculoskeletal fitness measures.
      All models included the effects of age, smoking status, body mass, and estimated
      VO2max as covariates, and the upper quartile was set as the reference group.
      RESULTS: There was no pattern of increased risk of mortality across quartiles of
      trunk flexibility or push-ups; however, there was a significantly higher risk in
      the lower quartile of sit-ups in both men (relative risk (RR) = 2.72, 95% CI 1.56
      4.64) and women (RR = 2.26, 95% CI 1.15-4.43). Grip strength was not predictive
      of mortality in women, although there was a 49% increased risk of death in the
      lower quartile of grip strength in males (RR = 1.49, 95% CI 0.86-2.59).
      CONCLUSION: The results suggest that some components of musculoskeletal fitness,
      particularly sit-ups (abdominal muscular endurance), are predictive of mortality
      in the Canadian population.

PMID- 11984289
TI  - Factors influencing exercise-related transient abdominal pain.
AB  - PURPOSE: Exercise-related transient abdominal pain (ETAP) is a widely experienced
      but poorly understood problem. This study examined the influence of age, gender,
      body mass index (BMI), training status, and sporting activity on the experience
      of ETAP and shoulder tip pain (STP). STP may occur as a result of referred pain
      from tissues innervated by the phrenic nerve; these tissues are implicated in
      theories proposed to explain ETAP. METHODS: A total of 965 regular sporting
      participants were surveyed from six sporting activities: running, swimming,
      cycling, aerobics, basketball, and horse riding. RESULTS: The prevalence (r = 
      0.28, P < 0.01) and severity (r = -0.17, P < 0.01) of ETAP decreased with age.
      Gender, BMI, and training status had no affect on the prevalence or severity of
      ETAP, but respondents who trained more frequently reported experiencing ETAP less
      often. Younger respondents were more inclined than the older respondents to
      report ETAP on the left side of the abdomen (P < 0.05). The prevalence (r = 
      0.11, P < 0.01) and severity (r = -0.37, P < 0.01) of STP decreased with age. STP
      was described as more severe (r = 0.23, P < 0.05) by respondents with high BMI
      values. Gender and training status had no influence on the experience of STP.
      Controlling for all other factors, ETAP was respectively 10.5 and 9 times more
      common (P < 0.01) in running and horse riding than cycling. STP was 13 times more
      common in running than cycling. CONCLUSION: Training status alters the frequency
      of occurrence of ETAP but has little effect on the incidence or severity of the
      pain. Further, ETAP and STP decrease with age but are not related to gender or
      BMI.

PMID- 11984290
TI  - Effect of pregnancy on heart rate/oxygen consumption calibration curves.
AB  - PURPOSE: The purpose of this investigation was to determine heart rate
      (HR)/oxygen consumption (VO2) calibration curves for exercising and sedentary
      women during pregnancy and the postpartum periods. METHODS: Fifty-two women were
      studied at three time points: 20 wk gestation, 32 wk gestation, and 12 wk
      postpartum. Subjects were grouped either as regular exercisers (N = 27) or
      sedentary controls (N = 25). At each time point, each woman had HR and VO2
      measured at rest (lying, seated, and standing) as well as during steady-state
      treadmill exercise performed at three increasing intensities. Flex HRs were
      defined and calculated by averaging the value seen during the lowest exercise
      intensity and highest value during rest. Individual HR/VO2 calibration curves
      were generated for exercise at each time point. Statistical analyses of all
      dependent variables included comparisons of subject groups (exercise and
      sedentary) and pregnancy status (20 wk, 32 wk, and 12 wk postpartum). RESULTS:
      Resting VO2 (mL.kg-1.min-1) was approximately 6.5% greater during pregnancy
      compared with postpartum conditions (P < 0.005). Also, both resting and flex HRs
      were greater during pregnancy compared with postpartum (P < 0.01). Resting HR was
      lower in exercising women compared with sedentary controls at all time points (P
      < 0.01). Slopes of HR/VO2 regression curves were flatter during pregnancy (P <
      0.005), but there was no difference between groups. Y-intercepts were less at 20
      wk compared with 36 wk postpartum. CONCLUSIONS: A woman's HR, VO2, and the
      relationship between these two parameters are altered during pregnancy. Change in
      slope of HR/VO2 regression curves indicates less energy expenditure at a given HR
      as pregnancy progresses, compared with postpartum conditions. A woman's true
      energy expenditure would be overestimated at rest, and underestimated during
      physical activity, if these physiological changes are not taken into account.

PMID- 11984291
TI  - Wheelchair propulsion technique and mechanical efficiency after 3 wk of practice.
AB  - PURPOSE: Differences in gross mechanical efficiency between experienced and
      inexperienced wheelchair users may be brought about by differences in propulsion
      technique. The purpose of this experiment was to study changes in propulsion
      technique (defined by force application, left-right symmetry, intercycle
      variability, and timing) and gross mechanical efficiency during a 3-wk wheelchair
      practice period in a group of novice able-bodied nonwheelchair users. METHODS:
      Subjects were randomly divided over an experimental group (N = 10) and a control
      group (N = 10). The experimental group received a 3-wk wheelchair practice period
      (3.wk-1, i.e., 9 practice trials) on a computer-controlled wheelchair ergometer,
      whereas the control group only participated in trials 1 and 9. During all nine
      practice trials, propulsion technique variables and mechanical efficiency were
      measured. RESULTS: No significant differences between the groups were found for
      force application, left-right symmetry, and intercycle variability. The push
      frequency and negative power deflection at the start of the push phase diminished
      significantly in the experimental group in contrast to the control group (P <
      0.05). Work per cycle, push time, cycle time, and mechanical efficiency
      increased. CONCLUSION: The practice period had a favorable effect on some
      technique variables and mechanical efficiency, which may indicate a positive
      effect of improved technique on mechanical efficiency. Although muscle activation
      and kinematic segment characteristics were not measured in the present study,
      they may also impact mechanical efficiency. No changes occurred over time in most
      force application parameters, left-right symmetry, and intercycle variability
      during the 3-wk practice period; however, these variables may change on another
      time scale.

PMID- 11984292
TI  - Vasomotor responses in glabrous and nonglabrous skin during sinusoidal exercise.
AB  - PURPOSE: To test whether vasomotor responses to dynamic exercise differ in
      glabrous and nonglabrous human skin, we determined the phase response and
      amplitude response of cutaneous vascular conductance in the forearm (CVCforearm),
      dorsal hand (CVCdorsal hand), and palm (CVCpalm) to sinusoidal exercise. METHODS:
      Nine healthy subjects exercised on a cycle ergometer with a constant load (35% of
      peak O2 uptake) for 20 min at an ambient temperature of 25 degrees C and relative
      humidity of 60%; for the next 40 min, they exercised with a sinusoidal load. The
      sinusoidal load variation ranged from 10% to 60% of peak O2 uptake over a 4-min
      period. Skin blood flow was monitored by laser-Doppler flowmetry. CVC was
      calculated from the ratio of blood flow to mean arterial pressure (MAP). RESULTS:
      During sitting rest and exercise, CVCpalm showed consistently higher value than
      CVCforearm and CVCdorsal hand. During sinusoidal exercise, the amplitude in
      CVCpalm was 7.4 times and 3.2 times greater than those in CVCforearm and
      CVCdorsal hand, respectively (P < 0.05). The phase difference in CVCforearm and
      CVCdorsal hand were smaller than that in CVCpalm (P < 0.05). CONCLUSION: These
      findings of significant differences in phase and amplitude of responses in CVC
      between glabrous and nonglabrous skin during cyclic changes of dynamic exercise
      load suggest functionally important differences in the reflex control of these
      regions of skin.

PMID- 11984294
TI  - Effects of reduced ambient temperature on fat utilization during submaximal
      exercise.
AB  - PURPOSE: The influence of cold air exposure on fuel utilization during prolonged
      cycle exercise was investigated. METHODS: Nine male subjects cycled for 90 min in
      ambient temperatures of -10 degrees C, 0 degrees C, 10 degrees C, and 20 degrees
      C. External work performed between conditions was constant. Mean oxygen
      consumption (VO2) over the 90 min in the 20 degrees C trial corresponded to 64 +/
      5.8% VO2peak. RESULTS: Although mean skin temperature was different between
      trials (P < 0.05), rectal temperatures were not different. At -10 degrees C and 0
      degrees C, the respiratory exchange ratio was higher compared with 10 degrees C
      and 20 degrees C (0.98 +/- 0.01 and 0.97 +/- 0.01 vs 0.92 +/- 0.01 and 0.91 +/-
      0.01; P < 0.05). The associated rates of fat oxidation were lower at -10 degrees
      C and 0 degrees C compared with 10 degrees C and 20 degrees C (0.15 +/- 0.06 and
      0.17 +/- 0.06 vs 0.35 +/- 0.06 and 0.40 +/- 0.04 g.min-1; P < 0.05). Blood
      glycerol was lower at -10 degrees C and 0 degrees C compared with 20 degrees C (P
      < 0.05); mean values were 0.13 +/- 0.0, 0.13 +/- 0.0, and 0.18 +/- 0.0 mmol.L-1
      for the -10 degrees C, 0 degrees C, and 20 degrees C trials, respectively. Mean
      VO2 was lower in the -10 degrees C trial than the 20 degrees C trial (2.53 +/-
      0.06 vs 2.77 +/- 0.09. L.min-1; P < 0.05). Mean blood glucose concentrations were
      lower at -10 degrees C than 20 degrees C (4.9 +/- 0.2 vs 5.3 +/- 0.1 mmol.L-1; P
      < 0.05). Although plasma epinephrine concentrations were greater during the 20
      degrees C trial compared with all other trials (P < 0.05), plasma norepinephrine
      did not differ between trials. CONCLUSION: The diminished fat oxidation at colder
      temperatures potentially reflects a reduction in lipolysis and/or mobilization of
      FFA or impairment in the oxidative capacity of the muscle.

PMID- 11984295
TI  - A muscle temperature compensation technique for EMG fatigue measures.
AB  - PURPOSE: The use of electromyogram-based fatigue measurements during high
      intensity, dynamic activities is confounded by the accompanying increase in
      muscle temperature. The purpose of this communication was to demonstrate the use
      of a muscle temperature compensation technique for electromyogram (EMG) fatigue
      measurements. METHODS: Subjects were six healthy men (mean age 30.8 +/- 5.6 yr)
      with no recent history of lower extremity injury. In part 1 of this study, the
      relationship between muscle temperature and EMG mean power frequency was
      determined for the vastus lateralis muscle (VL). The VL was heated with diathermy
      to a temperature of approximately 39 degrees C. Isometric EMG data were collected
      during the performance of a nonfatiguing protocol as the muscle cooled (39-34
      degrees C). In part 2 of this study, the subjects rode a lower-extremity
      ergometer at workloads of 25%, 50%, and 75% of their VO2max. Isometric EMG and
      intramuscular temperature data were collected from the VL during intermittent
      interruptions of the activity. The relationship between muscle temperature and
      EMG mean power frequency established in part 1 was used with the measured change
      in muscle temperature to correct for the effect of temperature on the EMG mean
      power frequency. RESULTS: The results from part 1 revealed a linear relationship
      between EMG mean power frequency and muscle temperature (N = 5, mean slope = 2.82
      +/- 0.27 Hz. degrees C-1, R2 = 0.88 +/- 0.02). The mean slope was used as a
      muscle temperature compensation factor that quantified the influence of muscle
      temperature on EMG mean power frequency. For part 2, representative data from a
      single subject are presented to demonstrate the use of the muscle temperature
      compensation technique. CONCLUSION: A muscle temperature compensation technique
      for EMG mean power frequency analysis has been demonstrated. This technique
      corrects for the detrimental influence of muscle temperature changes on EMG
      fatigue measurements, thereby improving the efficacy of EMG fatigue measurements
      during high-intensity, dynamic activities that result in muscle temperature
      increases.

PMID- 11984296
TI  - Inspiratory muscle fatigue in trained cyclists: effects of inspiratory muscle
      training.
AB  - PURPOSE: This study evaluated the influence of simulated 20- and 40-km time
      trials upon postexercise inspiratory muscle function of trained competitive
      cyclists. In addition, we examined the influence of specific inspiratory muscle
      training (IMT) upon the responses observed. METHODS: Using a double-blind placebo
      controlled design, 16 male cyclists (mean +/- SEM VO2max 64 +/- 2 mL.kg-1.min-1)
      were assigned randomly to either an experimental (IMT) or sham-training control
      (placebo) group. Maximum static and dynamic inspiratory muscle function was
      assessed immediately pre- and <2, 10, and 30 min post-simulated 20- and 40-km
      time trials before and after 6-wk of IMT or sham-IMT. RESULTS: Maximum
      inspiratory mouth pressure (P0) measured within 2 min of completing the 20- and
      40-km time trial rides was reduced by 18% and 13%, respectively, and remained
      below preexercise values at 30 min. The 20- and 40-km time trials induced a
      reduction in inspiratory flow rate at 30% P0 by 14% and 6% in the IMT group
      versus 13% and 7% for the placebo group, and also remained below preexercise
      values at 30 min. There was also a significant slowing of inspiratory muscle
      relaxation rate postexercise; these trends were almost completely reversed by 30
      min postexercise. Significant improvements in 20- and 40-km time trial
      performance were seen (3.8 +/- 1.7% and 4.6 +/- 1.9%, respectively; P < 0.05) and
      postexercise reductions in muscle function were attenuated with IMT. CONCLUSION:
      These data support existing evidence that there is significant global inspiratory
      muscle fatigue after sustained heavy endurance exercise. Furthermore, the present
      study provides new evidence that performance enhancements observed after IMT are
      accompanied by a decrease in inspiratory muscle fatigue.

PMID- 11984297
TI  - Decreased taurine concentration in skeletal muscles after exercise for various
      durations.
AB  - PURPOSE: To examine the changes of taurine concentrations in blood and skeletal
      muscles after transient exercise. METHODS: Rats were placed on a treadmill set at
      25 m.min-1. The animals were divided into four groups: control (no exercise) and
      exercise groups 1, 2, and 3. The exercise duration for groups 1, 2, and 3 was 30,
      60, and 100 +/- 12.5 min (to exhaustion: mean +/- SD), respectively. We examined
      the plasma concentrations of taurine and lactate, the serum concentrations of
      sodium and chloride ions, as well as the skeletal muscle taurine content in the
      soleus (slow-twitch fiber dominant type), gastrocnemius (slow- and fast-twitch
      fiber mix type), and plantaris and extensor digitorum longus (fast-twitch fiber
      dominant type) muscles. RESULTS: Although the plasma taurine concentration was
      not affected by the increased exercise duration, that in skeletal muscles was
      significantly decreased. The gastrocnemius and plantaris muscles from the
      exercise group 3 had a significantly lower concentration of taurine than those of
      the control group. The extensor digitorum longus taurine concentration from the
      different exercise groups was significantly decreased compared with that from the
      control group. However, there was no significant difference among the exercise
      groups. CONCLUSION: Taurine concentration was decreased in all skeletal muscles
      after exercise, regardless of the duration. Moreover, this decrease was specific
      to fast-twitch dominant fibers. However, under these conditions, the plasma
      taurine concentration remained unchanged.

PMID- 11984298
TI  - Contraction-induced muscle damage is unaffected by vitamin E supplementation.
AB  - PURPOSE: Vitamin E supplementation may confer a protective effect against
      eccentrically biased exercise-induced muscle damage through stabilization of the
      cell membrane and possibly via inhibition of free radical formation. Evidence
      supporting a protective role of vitamin E after contraction-induced muscle injury
      in humans is, however, inconsistent. The present study sought to determine the
      effect of vitamin E supplementation on indices of exercise-induced muscle damage
      and the postexercise inflammatory response after performance of repeated
      eccentric muscle contractions. METHODS: Young healthy men performed a bout of 240
      maximal isokinetic eccentric muscle contractions (0.52 rad.s-1) after being
      supplemented for 30 d with either vitamin E (N = 9; 1200 IU.d-1) or placebo (N =
      7; safflower oil). RESULTS: Measurements of torque (isometric and concentric)
      decreased (P < 0.05) below preexercise values immediately post- and at 48 h post
      exercise. Biopsies taken 24 h postexercise showed a significant increase in the
      amount of extensive Z-band disruption (P < 0.01); however, neither the torque
      deficit nor the extent of Z-band disruption were affected by vitamin E. Exercise
      resulted in increased macrophage cell infiltration (P = 0.05) into muscle, which
      was also unaffected by vitamin E. Serum CK also increased as a result of the
      exercise (P < 0.05) with no effect of vitamin E. CONCLUSION: We conclude that
      vitamin E supplementation (30 d at 1200 IU.d-1), which resulted in a 2.8-fold
      higher serum vitamin E concentration (P < 0.01), had no affect on indices of
      contraction-induced muscle damage nor inflammation (macrophage infiltration) as a
      result of eccentrically biased muscle contractions.

PMID- 11984299
TI  - Resistance exercise-induced hormonal responses in men, women, and pubescent boys.
AB  - PURPOSE: This study was designed to investigate the acute plasma catecholamine
      (CA) response to resistance exercise and its association with serum testosterone
      (TES), cortisol (COR), and growth hormone (GH) concentration changes. METHODS:
      Six men, six women, and six adolescent boys (14 +/- 0 yr) performed five sets of
      10 knee extensions with 40% of one-repetition maximum followed by two sets
      performed to exhaustion. Arterialized venous blood was sampled before, during,
      and after the exercise for the hormone analysis. External work performed (Wext),
      average EMG normalized for maximal EMG, exercise-induced maximal voluntary
      contraction decline, and plasma volume change (deltaPV) were also determined.
      RESULTS: No differences between groups were observed in Wext relative to lean
      body mass, average EMG, or in exercise-induced fatigue. Plasma norepinephrine
      (NE) concentrations were similar in the three groups. However, peak plasma
      epinephrine (E) increase from preexercise was about twice as high in boys (5.0 +/
      2.6 nmol.L-1 as in men (2.5 +/- 0.8 nmol.L-1] and in women (2.1 +/- 0.6 nmol.L
      1) (P < 0.05). The deltaPV could explain a significant increase in serum TES
      concentration in men, and increases in GH concentrations in every group, but not
      that of COR observed only in boys. No correlation between the CA concentration
      changes and those of the other hormones were observed even if the groups were
      combined. CONCLUSION: No associations between the CA and the other hormone
      responses were observed. However, the results may suggest a trend for higher
      stress response to this particular exercise in the boys than in adults.

PMID- 11984300
TI  - Relationship between physical activity and oxidative stress biomarkers in women.
AB  - PURPOSE: To examine the relationship between physical activity and levels of
      plasma lipid peroxides, superoxide dismutase in erythrocytes (SOD), and
      glutathione peroxidase (GSH-Px) in whole blood activities. METHODS: Cross
      sectional study in 488 Spanish women. Two categories of leisure time physical
      activity were defined according to their intensity: low (<or=6 METs) and high (>6
      METs). Energy expenditure in household activities was also recorded. Multivariate
      linear regression analyses were used to adjust for the effect of physical
      activity on lipid peroxides and SOD and GSH-Px for confounding variables.
      RESULTS: The amount of leisure time physical activity was associated with high
      activity levels of SOD (P = 0.022) and GSH-Px (P = 0.002). Similar results were
      obtained when physical activity in household activities was added to total
      leisure physical activity. Physical activity of low intensity was associated with
      high SOD activity levels (P = 0.002) and that of high intensity with high GSH-Px
      activity levels (P = 0.001). CONCLUSION: The amount and intensity of leisure
      physical activity were directly related to both antioxidant enzyme activity
      levels. The findings of this study suggest a modulatory effect of leisure
      physical activity intensity on antioxidative balance in the studied female
      population.

PMID- 11984301
TI  - Effects of resistance training on protein utilization in healthy children.
AB  - PURPOSE: Public health initiatives promote increased physical activity in
      children. More specifically, resistance training has recently received attention
      as an important component of youth fitness programs. The study examined the
      effect of this mode of exercise on protein utilization in young boys and girls.
      METHODS: Healthy children (N = 11, 8.6 +/- 1.1 yr, 33.7 +/- 9.4 kg, 131 +/- 9.6
      cm, BMI = 19.1 +/- 3.4) participated in a supervised resistance-training program
      2 times.wk-1 for 6 wk. 15N glycine methodology was used to assess nitrogen flux
      (Q), protein synthesis (PS), protein breakdown (PB), and net turnover ([NET] = PS
      - PB) before (PRE) and after (POST) resistance training. Percent body fat (%BF),
      fat-free mass (FFM), fat mass (FM), and energy and protein intakes were also
      determined. PRE/POST measurements of 1RM for the chest press and leg extension
      were used to examine strength gains. RESULTS: Gains associated with the chest
      press and leg extension were 10% and 75% (P < 0.001), respectively. Significant
      increases (P < 0.05) were noted for weight, height, FFM, and FM. Energy and
      protein intake remained constant. Significant decreases (PRE vs POST) were
      observed for Q (1.22 +/- 0.1 vs 0.75 +/- 0.05 gN.kg-1.d-1, P < 0.001), PS (6.48
      +/- 0.47 vs 3.55 +/- 0.30 g.kg-1.d-1, P < 0.001), and PB (5.24 +/- 0.41 vs 2.96
      +/- 0.30 g.kg-1.d-1, P < 0.01) after 6 wk of resistance training. NET was also
      reduced (P = 0.07, 1.24 +/- 0.31 vs 0.59 +/- 0.20 g.kg-1.d-1). CONCLUSIONS:
      Resistance training resulted in a downregulation in protein metabolism, which may
      be energy based. Future studies are needed to clarify energy, as well as protein,
      needs in young children participating in this form of exercise.

PMID- 11984302
TI  - Postexercise protein intake enhances whole-body and leg protein accretion in
      humans.
AB  - PURPOSE: Exercise increases the use of amino acids for glucose production and
      stimulates the oxidation of amino acids and other substrates to provide ATP for
      muscular contraction, and thus the availability of amino acids and energy for
      postexercise muscle protein synthesis may be limiting. The purpose of this study
      was to determine the potential of postexercise nutrient intake to enhance the
      recovery of whole-body and skeletal muscle protein homeostasis in humans.
      METHODS: Primed-continuous infusions of L-[1-13C]leucine and L-[ring
      2H5]phenylalanine were initiated in the antecubital vein and blood was sampled
      from a femoral vein and a heated (arterialized) hand vein. Each study consisted
      of a 30-min basal, a 60-min exercise (bicycle at 60% VO2max), and a 180-min
      recovery period. Five men and five women were studied three times with an oral
      supplement administered immediately following exercise in random order: NO = 0,
      0, 0; SUPP = 0, 8, 3; or SUPP+PRO = 10, 8, 3 g of protein, carbohydrate, and
      lipid, respectively. RESULTS: Compared to NO, SUPP did not alter leg or whole
      body protein homeostasis during the recovery period. In contrast, SUPP+PRO
      increased plasma essential amino acids 33%, leg fractional extraction of
      phenylalanine 4-fold, leg uptake of glucose 3.5-fold, and leg and whole-body
      protein synthesis 6-fold and 15%, respectively. Whereas postexercise intake of
      either NO or SUPP resulted in a net leg release of essential amino acids and net
      loss of whole-body and leg protein, SUPP+PRO resulted in a net leg uptake of
      essential amino acids and net whole-body and leg protein gain. CONCLUSIONS: These
      findings suggest that the availability of amino acids is more important than the
      availability of energy for postexercise repair and synthesis of muscle proteins.

PMID- 11984303
TI  - Epidemiology of musculoskeletal injuries among sedentary and physically active
      adults.
AB  - PURPOSE: This study describes the types and frequencies of musculoskeletal
      injuries among a cohort of adults with above average activity levels who were
      enrolled in the Aerobics Center Longitudinal Study (Dallas, TX). METHODS:
      Participants were adults aged 20-85 yr who completed a baseline clinical
      examination (1970-1982) and returned a mailed follow-up survey in 1986.
      Participants (5,028 men, 1,285 women) were measured for aerobic fitness, height,
      and body weight during the baseline examination. They reported detailed
      information about their physical activity levels and injury experiences on the
      follow-up survey (1986). An injury was defined as any self-reported soft tissue
      or bone injury that occurred within the previous 12 months. Activity-related
      injuries were those injuries participants attributed to participation in a formal
      exercise program. RESULTS: A quarter of all participants reported a
      musculoskeletal injury. Of these, 83% were activity-related. More than 66% of
      activity-related injuries occurred in the lower extremity; the knee was listed as
      the joint most often affected. There were no significant sex differences in the
      prevalence of injury, regardless of cause. Sport participants had the highest
      proportion of all-cause and activity-related musculoskeletal injuries among both
      men and women. Self-perceived severe injuries had a significant negative impact
      on physical activity levels since almost 1/3 of subjects reported permanently
      stopping their exercise program after injury. CONCLUSION: These results suggest
      the need for developing and implementing injury prevention programs targeted
      toward moderately active adults.

PMID- 11984304
TI  - Validation of the Godin-Shephard questionnaire in prepubertal girls.
AB  - PURPOSE: This study was designed to provide validation of the Godin-Shephard
      questionnaire for the assessment of habitual activity in prepubertal children.
      METHODS: Twenty-nine female competitive gymnasts and 32 recreational and
      nongymnasts, aged 7-11 yr, underwent multiple measures of physical activity over
      a 15 month period. The Godin-Shephard questionnaire (G-S) was completed once, in
      the middle of the study period. The Physical Activity Checklist Inventory (PACI)
      was completed 6 times, at intervals throughout the study, for 2 weekend days and
      4 weekdays. Caltrac activity monitors (Hemokinetics, Madison, WI) were worn by
      each subject in two waves consisting of 2 weekdays and 1 weekend day each. Self
      reported activity (h/wk) was recorded by the gymnasts in daily logs and for the
      nongymnasts through quarterly queries regarding participation in organized
      activities. A rank order was assigned to each subject for each tool. Spearman
      rank order correlations assessed the relationship between the G-S versus each
      measure and combination of measures. Subjects were also divided into gymnast and
      recreational/nongymnast groups, and alternately into 7-9 yr old and >or= 10 yr
      old groups, re-ranked and re-analyzed. RESULTS: The average rank of combined
      PACI, Caltrac and h/wk scores showed only moderate correlation with ranked G-S
      scores for the overall group and for the 7-9 yr old subset, rho = 0.380 (P =
      0.003) and rho = 0.422 (P = 0.043), respectively. The average rank of combined
      PACI and Caltrac scores also showed only moderate correlation with the ranked G-S
      scores for the gymnast subset, rho = 0.423 (P = 0.025). No measure or combination
      of measures correlated significantly with the ranked G-S scores for the >or= 10
      yr old subset or the nongymnast subset. CONCLUSION: Based upon comparison with
      multiple single day measures of activity, the G-S did not provide a good estimate
      of habitual activity in preadolescent females.

PMID- 11984305
TI  - Resistance training alters torque-velocity relation of elbow flexors in elderly
      men.
AB  - PURPOSE: The aim of the study was to compare in vivo dynamic muscle
      characteristics (torque-velocity relation and maximal contraction velocity) of
      sedentary young subjects with elderly men before and after training. METHODS:
      Elbow flexion maximal isometric (Tmax) and dynamic torque at velocities between
      100 degrees.s-1 and 600 degrees.s-1 were measured, from which maximal contraction
      velocity was estimated (eVmax). These parameters were obtained from 18 young
      sedentary subjects (Y) and from 23 healthy sedentary elderly (mean age 63 yr) men
      (E) before (PRE), after 13 wk (MID), and 26 wk (POST) of moderate intensity
      resistance training (30RM) of the elbow flexor muscles. RESULTS: Y and E before
      training had similar Tmax, but mean dynamic torque over all velocities was 49.1%
      higher in Y compared with E. After 13 wk of training TmaxE increased by 8.2% and
      mean dynamic torque increased by 61.2%, with a velocity dependent gain. For
      eVmaxE an increase of 21.8% was observed. The second 13-wk training period did
      not induce further increases. CONCLUSION: The results of the present study
      demonstrate that, after moderate intensity resistance training of healthy elderly
      men, maximal contraction velocity of elbow flexors (eVmax), estimated from the
      torque-velocity curve, increased to values observed for sedentary young men.

PMID- 11984306
TI  - Electromyographic (EMG) normalization method for cycle fatigue protocols.
AB  - PURPOSE: To determine the most effective electromyographic (EMG) normalization
      method for cycling fatigue protocols. METHODS: Ten healthy subjects performed two
      5-s isometric knee extension maximal voluntary contractions (MVC) at a knee joint
      angle of 60 degrees, two fixed cycle pedal contraction at knee joint angles of 60
      degrees (60 degrees A) and 108 degrees (108 degrees A), and a dynamic single
      maximal revolution of a cycle pedal (1REV). Integrated EMG (IEMG) data were
      recorded for all contractions and power output recorded during MVC and 1REV.
      RESULTS: Mean IEMG for MVC was significantly (P < 0.01) greater than 60 degrees
      C, 108 degrees C, and 1REV. There were no significant differences between MVC and
      1REV power output/EMG relationship. CONCLUSIONS: MVC will record a higher IEMG
      than 60 degrees A, 108 degrees A, and 1REV. As IEMG was greatest during MVC, and
      the relationship between IEMG and power output was not different between MVC and
      1REV, normalization against maximal possible recruitment potential is most likely
      during MVC.

PMID- 11984307
TI  - Perceived exertion responses to novel elbow flexor eccentric action in women and
      men.
AB  - PURPOSE: The primary aim was to describe perceived exertion responses to
      different intensities of eccentric exercise in women and men. METHODS: 42 adults
      (21 men and 21 women, 7 per condition) completed elbow extension exercises with a
      weight corresponding to 80%, 100%, or 120% of maximal voluntary concentric
      strength. Total work was equated by manipulating the number of repetitions in the
      80% (N = 45), 100% (N = 36), and 120% (N = 30) conditions. RESULTS: A two-way
      ANOVA showed significant main effects for the intensity and sex factors.
      Perceived exertion ratings were strongly dependent on exercise intensity, and
      women reported lower RPEs than men. A separate three-way mixed model ANOVA that
      included a repetition factor showed that perceived exertion ratings increased
      similarly across the first 30 repetitions in all exercise conditions. Significant
      partial correlations were found between mean RPE during the eccentric exercise
      bout, and the mean intensity of delayed-onset muscle pain measured from 12- to 72
      h postexercise after controlling for the relative exercise intensity (r12.3 =
      0.28) or the maximum concentric strength of the elbow flexors (r12.3 = 0.33).
      CONCLUSIONS: 1) for both women and men, there is a positive association between
      the intensity of eccentric exercise performed with the elbow flexors and RPE; 2)
      perceived exertion ratings increase significantly then plateau when repeated
      eccentric muscle actions are performed at constant, submaximal absolute
      intensities; 3) women rate eccentric exercise performed at the same intensity
      (relativized to MVC-C) as being less effortful compared with men; and 4) RPE
      during eccentric exercise can account for a small but significant amount of
      variability in delayed-onset muscle pain after statistically controlling for
      differences in strength or relative intensity.

PMID- 11984308
TI  - Hematological indices and iron status in athletes of various sports and
      performances.
AB  - PURPOSE: Alterations of the red blood cell system and iron metabolism can
      influence physical performance. On the other hand, exercise can influence
      hematological variables. The purpose of this epidemiological study was to
      investigate the characteristics of the red blood cell system and the iron
      metabolism in athletes of different sporting disciplines and at different levels
      of performance. METHODS: We studied 851 male subjects (747 athletes, 104
      untrained controls). Hemoglobin (Hb), hematocrit (Hct), red blood cell count
      (RBC), iron, transferrin, ferritin (Fer), and haptoglobin were analyzed in
      standardized blood samples, obtained after 2 d of rest, considering levels of
      performance (internationally, nationally, locally competitive, and leisure time),
      distinctive sporting category (endurance- (END), strength- (POW), and mixed
      trained (MIX)), and, within endurance athletes, distinctive disciplines (cycling
      (CYC) and running (RUN)). RESULTS: No difference was found between athletes and
      controls in Hb and Hct. Reduced Hb, Hct, and RBC levels were observed in END
      compared with POW and MIX. These findings can mainly be attributed to exercise
      induced plasma volume expansion, and only to a lesser degree and in selected
      athlete populations to hemolysis, as low haptoglobin is only observed in RUN, not
      in CYC, suggesting that not exercise itself but the "traumatic" movement of
      running might trigger the destruction of red blood cells. Physical activity of
      increasing duration and workloads (leisure time compared with competitive
      athletes) leads to decreased Fer levels in athletes, disregarding their
      discipline, but more pronounced in RUN. CONCLUSION: Physical training itself has
      no significant effect on selected hematological variables in athletes compared
      with untrained controls. The specific type and duration of exercise is of major
      importance in the adaptations of the blood cell system and the iron metabolism.

PMID- 11984309
TI  - Increased body iron stores in elite road cyclists.
AB  - BACKGROUND: One third of French elite road cyclists were found to have
      hyperferritinemia on antidoping control tests performed during the Tour de France
      in 1998. PURPOSE: This study was undertaken to determine whether
      hyperferritinemia corresponded to elevated body iron stores or not and,
      affirmatively, what were its mechanism, its clinical consequences, and its
      spontaneous course. METHODS: 83 elite road male cyclists presenting with
      hyperferritinemia, defined as serum ferritin level greater than 300 microg.L-1,
      were studied with respect to consumption of iron and other drugs, serum iron
      tests, HFE mutations, and hepatic iron concentration (HIC; N < 35 micromol.g-1
      dry weight). RESULTS: All cyclists were asymptomatic and had normal physical and
      cardiac examination. Their median (range) serum ferritin, serum iron, and
      transferrin saturation levels were 504 microg.L-1 (306-1671), 20 micromol.L-1
      (8.5-36.3), and 39% (20-76), respectively. HIC was increased in 24/27 up to 187
      micromol.g-1. Allelic frequency of the H63D mutation was increased in cyclists
      when compared to controls (P = 0.04). However, iron tests did not differ
      according to HFE genotypes. Most cyclists (89%) had been supplemented with iron.
      The median iron supplementation was 25.5 g (range: 1.4-336) and correlated well
      (P = 0.002) with serum ferritin. Evolution of serum ferritin levels did not
      differ whether cyclists had been continuing iron supplementation or not.
      CONCLUSION: Hyperferritinemia in elite road cyclists accounted for increased body
      iron stores caused by and persisting after cessation of excessive iron
      supplementation. Even when mild, iron excess may expose to long-term
      complications and should be removed, at least at the time when professional
      cyclists retire. To prevent iatrogenic iron overload, supplementation with iron
      must be done according to serum ferritin follow-up and not either blindly or on
      the basis of serum iron determination only.

PMID- 11984310
TI  - Heart rate prescriptions from performance and anthropometrical characteristics.
AB  - PURPOSE: Heart rate (HR) is widely used to adjust exercise intensity in aerobic
      training. Training HR recommendations are calculated often from simple equations.
      Because at lactate steady state (LASS) may be an intensity of exercise eliciting
      similar objective measures of intensity and similar subjective measures of
      metabolism, it is an appropriate intensity upon which to base aerobic-training
      prescription. The purpose of this research was to develop regression equations
      using age and other easily accessible characteristics to estimate the HR
      associated with LASS (HRLASS). METHODS: The data of 7397 healthy subjects (age
      >or= 10 yr; 5044 male, 2353 female) with different training habits were analyzed.
      All participants were tested in an incremental exercise test on the treadmill
      until subjective exhaustion. The LASS was determined by the concept of blood
      lactate at the "lactate threshold" plus a net increase of 1.5 mmol.L-1. The
      interdependence of further characteristics was tested by stepwise multiple
      regression. RESULTS: Age alone did not allow a precise prediction of
      lass=hText>HRLASS (r = 0.645 for all participants), regardless of adjustment by
      sex, training state, body mass, or performance characteristics using ANCOVA.
      Resting HR (HRrest) decreased steeply within the second life decade but not with
      further advancing age. The best discrete lactate-independent predictor for HRLASS
      was HRmax (r = 0.798). Inclusion of age and weight in the model resulted in only
      a small improvement of the prediction (r = 0.826). Other anthropometrical
      characteristics could not improve the model further. CONCLUSIONS: The use of age
      alone seems too imprecise for exactly driven aerobic training prescriptions. A
      minor improvement can be achieved in this objective by use of HRmax supplemented
      by age using a multiple regression model.

PMID- 11984311
TI  - Validity of the simultaneous heart rate-motion sensor technique for measuring
      energy expenditure.
AB  - PURPOSE: To determine the validity of the simultaneous heart rate-motion sensor
      (HR+M) technique for estimating energy expenditure (EE) by comparing it with
      indirect calorimetry. In addition, we examined the validity of the flex heart
      rate (FlexHR) method to estimate EE. METHODS: Ten participants (4 men: 26.7 yr +/
      1.5, and 6 women: 26.5 yr +/-3.3) performed arm and leg work in the laboratory
      for the purpose of developing individualized HR-oxygen uptake (VO2) regression
      equations. Participants completed physical tasks in a field setting while HR,
      VO2, and motion sensor data were collected on a near-continuous basis for 6 h.
      Accelerometers, one on the arm and one on the leg, were used to discriminate
      between upper- and lower-body movement. HR was used to predict EE (METs) from the
      corresponding laboratory regression equation. Predicted values (METs) were
      compared with measured values (METs) obtained via a portable metabolic
      measurement system. RESULTS: The simultaneous HR+M technique showed a
      significantly stronger relationship with VO2 (R2 = 0.81, SEE = 0.55 METs) in
      comparison with the FlexHR method (R2 = 0.63, SEE = 0.76 METs) (P < 0.001). The
      FlexHR method significantly overestimated measured minute-by-minute EE (P <
      0.001), whereas the simultaneous HR+M technique did not. The simultaneous HR+M
      technique accurately reflected time spent in resting/light, moderate, and hard
      activity, whereas the FlexHR method underpredicted time spent in resting/light
      activity (P = 0.02) and overpredicted time spent in moderate activity (P = 0.02).
      The simultaneous HR+M technique also accurately estimated total 6-h EE.
      CONCLUSION: The simultaneous HR+M technique is an accurate predictor of EE during
      free-living activity and provides a valid measure of the time spent in various
      intensity categories.

PMID- 11984312
TI  - Determining energy expenditure during some household and garden tasks.
AB  - PURPOSE: This study: a) calculated the reproducibility (intraclass correlation
      coefficient, ICC) and precision (technical error of measurement, TEM) for VO2
      during moderate paced walking, self-paced sweeping, window cleaning, vacuuming
      and lawn mowing; b) determined which of the five activities rated >or= 3.0 when
      exercise intensity was calculated in METs (1 MET or metabolic equivalent = VO2 of
      3.5 mL.kg-1.min-1) and multiples of the measured resting metabolic rate (RMR);
      and c) expanded the limited database on energy expenditure during household and
      garden activities. METHODS: Twelve men and 12 women (mean +/- SD: 39.3 +/- 3.4
      yr; 171.6 +/- 9.6 cm; 81.0 +/- 15.5 kg) were measured for RMR and VO2 during the
      five activities on two separate days via indirect calorimetry by using the
      Douglas bag method. RESULTS: The interday ICCs and TEMs for the five activities
      ranged from 0.81 to 0.97 and from 2.1 to 7.0%, respectively. The means were
      significantly (P < 0.001) above 3.0 for moderate paced walking (range = 3.3-8.7),
      sweeping (2.9-6.7), window cleaning (3.0-6.0), vacuuming (2.6-4.4), and lawn
      mowing (4.9-7.5) when VO2 was divided by measured RMR, but one and five subjects
      scored below 3.0 for sweeping and vacuuming, respectively. Division of exercise
      VO2 by the convention of 3.5 mL O2.kg-1.min-1 significantly decreased (P < 0.001)
      each mean, and lawn mowing (5.0 METs) was the only activity where all subjects
      scored above 3.0 METs (P < 0.001; 3.8-6.4); nevertheless, the means for walking
      (3.7 METs), sweeping (3.2 METs), and window cleaning (3.6 METs) were also in the
      moderate intensity category of 3-6 METs. CONCLUSIONS: These data: a) emphasize
      that the VO2 during self-paced moderate intensity walking and self-paced
      household and garden activities can be measured with reproducibility and
      precision, b) demonstrate that expressing energy expenditure in conventional METs
      yields lower values than when it is presented as a multiple of measured RMR, c)
      suggest that all activities except vacuuming are performed at moderate intensity
      when energy expenditure is expressed in conventional METs, and d) highlight the
      biological variability in energy expenditure when different people perform the
      same task.

PMID- 11984314
TI  - A New Year's resolution: safety first!

PMID- 11984316
TI  - Winning the "blame game".
AB  - Promoting trust within an organization involves doing away with the culture of
      blame that surrounds medical errors. When nurses feel safe to report errors and
      near misses, nurse leaders can identify weak areas and strengthen systems.

PMID- 11984317
TI  - Let's bring down age retention barriers.

PMID- 11984321
TI  - Sedation, anesthesia update.
AB  - JCAHO surveyors have scored the revised Sedation and Anesthesia Care Standards
      since January 2000, resulting in insufficient evidence of hospital compliance.

PMID- 11984322
TI  - Report impaired practice--stat.
AB  - Don't hesitate to report substance abuse and mental illness-doing so often
      initiates the treatment process for valued staff.

PMID- 11984323
TI  - Searching for nursing's future? Here's how to turn your vision into reality.
AB  - Nurses from the Inova Health System, an integrated care system in northern
      Virginia, used the Future Search process to create an action plan for their
      future practice.

PMID- 11984324
TI  - Staff development special: spinal anesthesia and analgesia.
AB  - When caring for a patient who's received drugs intrathecally, teach staff how to
      assess his condition, anticipate and recognize problems, and intervene correctly.

PMID- 11984326
TI  - Cut to the chase.

PMID- 11984327
TI  - A decent proposal.

PMID- 11984330
TI  - The magnetic pull: top Magnet plan administrators share how their organizations
      achieved nursing's highest honor.
AB  - First in a continuing series of articles, discover the major attributes of
      organizations that earn Magnet status through The Magnet Nursing Services
      Recognition Program for Excellence in Nursing Services of the American Nurses
      Credentialing Center.

PMID- 11984331
TI  - Bioterrorism's invisible threats: heightened awareness will help nurses identify
      real and suspected bioterrorism.
AB  - Ready your nursing staff for potential bioterrorism with this review of the
      symptoms and treatment of anthrax, smallpox, plague, tularemia, and botulism.

PMID- 11984332
TI  - Say it with a smile.

PMID- 11984333
TI  - Get customer sensitive.

PMID- 11984334
TI  - Point-of-care: in vivo technology.
AB  - In vivo testing offers disease management with real-time results.

PMID- 11984338
TI  - Put the progress in progressive care.

PMID- 11984339
TI  - How to slash costly turnover.
AB  - Enhance retention efforts to help lower the hefty price tag of staff turnover.

PMID- 11984340
TI  - New direction, same road.
AB  - New managers rely on solid competency to rise to new challenges.

PMID- 11984341
TI  - Give the gift of gratitude.

PMID- 11984345
TI  - Watch it drop!

PMID- 11984346
TI  - Sift with savvy.

PMID- 11984348
TI  - Once isn't enough when measuring staff competence.
AB  - Certain aspects of evaluating competence are ongoing, at the very least, once
      within the 3-year accreditation cycle.

PMID- 11984349
TI  - A liability checklist for clinical pathways.
AB  - To ensure safe, responsible use of clinical pathways, follow written policies and
      procedures and document all patient care.

PMID- 11984350
TI  - Progressive care series. Part 1. Keep with step-down care.
AB  - Progressive care units provide care to stable, critically ill patients of varying
      acuities. Managers of these diverse units must consider care delivery systems,
      staffing, technology, acuity measurement, and regulatory issues.

PMID- 11984352
TI  - Staff development special: a new beat for BLS and ACLS guidelines.
AB  - Under new basic life support guidelines, stroke victims receive the same priority
      care as those having a heart attack. Revised advanced cardiac life support
      guidelines encompass changes to algorithms and policies.

PMID- 11984353
TI  - Solutions success: clinical documentation technology.
AB  - Informatics and computerization offer reliable solutions for numerous health care
      needs. The challenge is acclimating staff to this process change.

PMID- 11984354
TI  - The ripple effect: it's time for health care leaders to address staff concerns
      following restructuring.
AB  - The degree of support an organization shows during periods of restructuring and
      downsizing greatly impacts staff stress levels and work environment perception.

PMID- 11984355
TI  - Soar to excellence with rapid feedback and rapid response.
AB  - Understanding the health care market requires understanding its customers as
      people, not as patients.

PMID- 11984356
TI  - APN spells success for a heart failure program.
AB  - Review the relationship between advanced practice nurse-directed heart failure
      programs and patient length of stay, mortality, re-admission rate, and adherence
      to recommended clinical regimens.

PMID- 11984357
TI  - Optimal infusion therapy? Overcome occlusions.
AB  - Identify, prevent, or manage the etiology of central vascular access device
      (CVAD) occlusions to promote better treatment outcomes, shorter hospital stays,
      and reduced care costs.

PMID- 11984375
TI  - Research vulnerability and patient advocacy: balance-seeking perspectives for the
      clinical nurse scientist?

PMID- 11984376
TI  - The management of surgical drains in plastic surgical units.

PMID- 11984377
TI  - Health disparities among vulnerable populations: evolution of knowledge over five
      decades in Nursing Research publications.
AB  - BACKGROUND: Considerable attention has been focused recently on conducting
      research on the health disparities experienced by some Americans as the result of
      poverty, ethnicity, and/or marginalized social status. Nursing research has a
      major role to play in developing this body of knowledge. PURPOSE: The purpose of
      this paper is to review the contributions that Nursing Research made through its
      publications over the last five decades in developing the body of tested
      knowledge about health disparities in vulnerable groups and to analyze the
      progress made. METHODS: Criteria for reviewing the literature were established.
      All Nursing Research publications between 1952 and 2000 were searched manually,
      indexes of each year's bound volumes were reviewed, and computer searches were
      conducted. Included in the review were research reports, research briefs, and
      methodology articles. RESULTS: Seventy-nine papers were found that met basic
      criteria for inclusion. The number of relevant publications increased each
      decade, with a sizable increase in numbers since 1990, and may be related to the
      social, political, and economic climate of each decade. The research questions
      asked and the methods used became more complex over time. CONCLUSIONS: Nursing
      Research has made a significant contribution in disseminating the body of tested
      knowledge related to the health disparities experienced by vulnerable populations
      and the methodologies associated with vulnerable populations research. Areas for
      future research are community-based studies, intervention studies that provide
      tangible resources, and methodologic approaches that involve participants in the
      research process.

PMID- 11984378
TI  - Self-efficacy and perceived exertion of girls during exercise.
AB  - BACKGROUND: An important national goal in Healthy People 2010 is to reduce the
      high prevalence of sedentary lifestyles and resultant overweight and obesity
      among girls. OBJECTIVES: The purpose of the present study was threefold: (a) to
      determine if pre-exercise self-efficacy predicted girls' perceptions of exertion
      during exercise, (b) to determine if these perceptions, in turn, influenced
      postexercise self-efficacy, and (c) to assess if exercise self-efficacy increased
      following completion of an exercise task. METHODS: A sample of 103 girls, 8 to 17
      years of age, pedaled 20 minutes on a cycle ergometer at 60% of their
      predetermined peak VO2 in a climatic chamber (90 degrees F, 50% relative
      humidity). Ratings of perceived exertion were obtained every 4 minutes. Exercise
      self-efficacy was assessed before and after the exercise session. RESULTS:
      Controlling for peak VO2 and percent body fat, pre-exercise efficacy exerted an
      independent effect on perception of exertion during exercise with girls high on
      pre-exercise self-efficacy reporting lower perceived exertion during exercise,
      than girls low on self-efficacy. Both pre-exercise efficacy and perceived
      exertion explained postexercise efficacy. Exercise self-efficacy increased
      significantly from pre- to postexercise. CONCLUSIONS: Pre-exercise efficacy is an
      important factor influencing girls' perceptions of exertion during exercise and
      their postexercise efficacy. Increased exercise self-efficacy of girls following
      successful completion of an exercise challenge suggests possible strategies to
      increase physical activity.

PMID- 11984379
TI  - Dysphoria among high-risk pregnant hospitalized women on bed rest: a longitudinal
      study.
AB  - BACKGROUND: While approximately 700,000 women experience pregnancy complications
      and are treated with bed rest in the hospital each year, little is known about
      negative affect in these women. OBJECTIVES: The study purpose was to describe
      dysphoria, a composite of symptoms of negative affect across the antepartum and
      postpartum and to identify the relationship between dysphoria and the length of
      pre-admission home bed rest, hospital bed rest, and maternal and fetal/neonatal
      indices of risk. METHODS: The convenience sample for this longitudinal repeated
      measures study consisted of 63 high-risk pregnant women admitted on antepartum
      bed rest to one of three university-affiliated hospitals. Women were included if
      they were diagnosed with (a) preterm labor, (b) premature rupture of membranes,
      (c) incompetent cervix, (d) placenta previa, (e) placental abruption or multiple
      gestation, and (f) did not have a psychiatric disorder. The Multiple Affect
      Adjective Checklist-Revised (MAACL-R) was used to assess dysphoria. Obstetric
      risk status was assessed by both the Hobel and Creasy Risk Assessment tools.
      RESULTS: Dysphoria was highest upon hospital admission and decreased
      significantly across time (F (5) = 23.58, p <.001). Positive Affect-Sensation
      Seeking significantly increased across time (F (5) = 53.16, p <.001). Dysphoria
      scores were significantly greater for those with highest Hobel obstetric risk
      scores (F (1, 60) = 4.53, p =.037). Antepartum dysphoria was not correlated with
      gestational age upon hospital admission, length of bed rest, or Creasy risk
      status. However, gestational age at birth was significantly correlated with
      postpartum dysphoria. DISCUSSION: The stimulus for antepartum dysphoria is
      unclear. However, postpartum dysphoria appears to be related to indicators of the
      infant's state of health at birth.

PMID- 11984380
TI  - Explaining Mexican American workers' hearing protection use with the health
      promotion model.
AB  - BACKGROUND: Mexican American workers are vulnerable to noise-induced hearing
      loss, the most common occupational disease in the United States. OBJECTIVES: The
      purpose was to test the applicability of the Health Promotion Model to Mexican
      American workers' use of hearing protection devices. METHOD: A correlational
      descriptive design and path analysis were used to determine the relationships
      between cognitive-perceptual factors, modifying factors and use of hearing
      protection devices. A questionnaire was completed by a total of 119 workers in
      three garment manufacturing plants. Interviews were conducted with the
      occupational health nurse or safety director in each plant to determine the
      policy regarding hearing protection also. RESULTS: Factors that directly
      influenced the use of hearing protection devices were a clinical definition of
      health, benefits of and barriers to use of hearing protection devices, self
      efficacy in the use of hearing protection devices and perceived health status (R2
      =.25, p <.01). An exploratory analysis allowing a direct relationship of
      modifying factors with the dependent variable explained additional variance in
      use of hearing protection devices through the contribution of situational factors
      (R2 =.55, p <.01). CONCLUSIONS: Important factors related to Mexican American
      workers' use of hearing protection devices were identified to provide direction
      for nursing interventions. Future research should further test the explanatory
      capabilities of the Health Promotion Model, explore the importance of situational
      influences on health behavior, and ensure reliable measures of all model
      components for this population.

PMID- 11984381
TI  - Describing an episode of home nursing care for elderly postsurgical cancer
      patients.
AB  - BACKGROUND: While studies have documented the beneficial effect of home care for
      cancer patients, the actual interventions implemented during these studies have
      not been well described. OBJECTIVES: Purposes of this study were to analyze
      interventions documented in narrative form by advanced practice nurses during a
      four-week episode of home care and describe intervention type, frequency, range,
      and variation over time in intervention emphasis and dose intensity. METHODS:
      Chart audits were performed on records kept for 148 postsurgical cancer patients
      who were assigned to the experimental group in a randomized clinical trial to
      evaluate the effect of home care on quality of life outcomes (McCorkle et al.,
      2000). Interventions statements (N = 7,275) were analyzed using Grobe's (1996)
      Nursing Intervention Lexicon and Taxonomy. RESULTS: Teaching accounted for the
      highest percentage of interventions documented, followed by provision of
      psychological support and reassurance, determination of patient needs and nursing
      care requirements, assessment of current status, and indirect care. Physical care
      and actions to promote self-care independence were documented least frequently.
      Differences in nursing care were found by cancer site with the greatest diversity
      of interventions documented for breast cancer patients. Intervention emphasis and
      dose intensity varied over time, suggesting that these nurses altered their care
      in response to the changing needs of their patients. CONCLUSIONS: These nurses
      responded to complex problems and used a variety of interventions to assist
      patients and families in management of the illness experience. They also tailored
      their care to each patient's location along the illness trajectory. These
      findings provide beginning support for the clinical utility of Nursing
      Intervention Lexicon and Taxonomy as a way to quantify an episode of nursing
      care.

PMID- 11984382
TI  - Reducing venipuncture and intravenous insertion pain with eutectic mixture of
      local anesthetic: a meta-analysis.
AB  - BACKGROUND: The eutectic mixture of local anesthetics (EMLA), by producing dermal
      anesthesia through contact with intact skin, has become a major indication for
      the reduction of pain experienced during venipuncture (VE) and intravenous (IV)
      insertion. OBJECTIVES: The purpose of the study was to determine the mean effect
      sizes and moderators of EMLA cream application in reducing VE and IV insertion
      pain. METHOD: A meta-analysis of 20 studies was conducted to determine the
      magnitude of the effect of EMLA cream on VE and IV insertion pain. Effect sizes
      were calculated three ways: weighted, unweighted, and weighted by quality index
      score. Potential moderating variables of sample age, premedication, therapist
      control, insertion site, application duration, research design, pain scale, and
      funding, were investigated for their influence on EMLA's effect. RESULTS: EMLA
      cream had a large significant effect on VE pain (d = 1.05) with a 95% confidence
      interval from.92 to 1.34 and a large significant effect on IV insertion pain (d =
      1.04) with a 95% confidence interval from.84 to 1.46. Subject age (child versus
      adult), type of pain scale, number of therapists, location of insertion site,
      premedication, funding, or study design did not appear to act as effect
      modifiers. CONCLUSIONS: EMLA cream can significantly decrease VE and IV insertion
      pain in 85% of the population.

PMID- 11984384
TI  - Maintaining data integrity in randomized clinical trials.
AB  - BACKGROUND: The process of attaining and maintaining data integrity is critical
      to ensure a successful randomized clinical trial. Methodologic strategies to
      achieve data integrity when repeated measures are used has not been discussed in
      detail in the literature. The National Institutes of Health requires that data
      integrity and safety monitoring boards or plans be established for randomized
      clinical trials. OBJECTIVES: The objectives of this paper are to (a) examine
      important data collection issues nurse scientists often encounter in randomized
      clinical trials and (b) present a process that researchers can apply to achieve
      data integrity. METHODS: The process to achieve data integrity is based on
      strategies that were developed by an interdisciplinary hospice research team
      involved in an ongoing National Institutes of Health-funded clinical trial. The
      process and key issues are illustrated with methodologic examples from the
      randomized clinical trial and supporting literature. RESULTS: The process of
      achieving data integrity involves developing protocols in three key areas: data
      collection, training of data collectors, and data monitoring. The use of these
      protocols will increase the rigor of the clinical trial and assist in maintaining
      study validity. CONCLUSIONS: Investigators conducting clinical trials need to
      consider all issues involved in achieving data integrity and have tested
      protocols in place throughout the study. These approaches will not only help
      maintain study validity but also help ensure data of sufficient quantity and
      quality to achieve the desired statistical power.

PMID- 11984383
TI  - Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and
      vomiting.
AB  - BACKGROUND: The mechanisms for postoperative nausea and vomiting are numerous and
      pathways not well elucidated. Although many medications have been developed to
      help prevent postoperative nausea and vomiting, the search for better approaches
      to recovery treatment continues. OBJECTIVE: The purpose of this study was to
      evaluate the effectiveness of isopropyl alcohol (IPA) inhalation for treatment of
      postoperative nausea and vomiting for patients who have general anesthesia for a
      surgical procedure. METHOD: Participants were recruited from an urban hospital on
      the East Coast of the United States. Participants were assigned to an
      experimental or control group and IPA inhalation was compared to the standard
      anti-emetic treatment for rescue treatment in the immediate postoperative period.
      Postoperative nausea and vomiting was rated using a descriptive ordinal scale.
      RESULTS: The results of this study show IPA to be effective and that there was no
      significant difference between the standard treatment protocol and treatment with
      IPA. Treatment with IPA was significantly more cost effective than standard drug
      treatment. DISCUSSION: Further research is recommended to evaluate the length of
      effectiveness, standard dose needed, most effective mode of inhalation, and
      factors blocking IPA effectiveness.

PMID- 11984385
TI  - The operations manual: a mechanism for improving the research process.
AB  - BACKGROUND: The development and use of an operations manual has the potential to
      improve the capacity of nurse scientists to address the complex, multifaceted
      issues associated with conducting research in today's healthcare environment. An
      operations manual facilitates communication, standardizes training and
      evaluation, and enhances the development and standard implementation of clear
      policies, processes, and protocols. A 10-year review of methodology articles in
      relevant nursing journals revealed no attention to this topic. OBJECTIVES: This
      article will discuss how an operations manual can improve the conduct of research
      methods and outcomes for both small-scale and large-scale research studies. It
      also describes the purpose and components of a prototype operations manual for
      use in quantitative research. CONCLUSION: The operations manual increases
      reliability and reproducibility of the research while improving the management of
      study processes. It can prevent costly and untimely delays or errors in the
      conduct of research.

PMID- 11984386
TI  - Academics that fail the grade: the CREST factors.

PMID- 11984387
TI  - A joint junior-senior clinical experience.

PMID- 11984388
TI  - Preceptor programs: increasing student self-confidence and competency.

PMID- 11984389
TI  - Faculty/student collaboration: an approach to teaching nursing research.

PMID- 11984390
TI  - Two views on clinical rotations: different students each time or always the same?

PMID- 11984391
TI  - Shaping the future of nursing education in Ireland.

PMID- 11984392
TI  - Outcomes of critical thinking and professional attitudes in RN/BSN completion
      programs.

PMID- 11984393
TI  - Assessing computer projection technology needs.
AB  - Computer projection technology is a widely accepted tool for delivering
      presentations. Many educators are responsible for purchasing the equipment for
      their departments to use, however, deciding which product to buy can be
      overwhelming. The authors present an overview of essential factors to consider
      when examining computer projectors. Also included is a 4-step process to assist
      educators when making these purchasing decisions.

PMID- 11984394
TI  - The 4 Cs: a model for teaching dosage calculation.
AB  - Performing dosage calculation can be viewed as the ability to perform the 4 Cs:
      compute, convert, conceptualize, and critically evaluate. Ability to perform the
      4 Cs is dependent on a variety of student and program factors. A model for
      teaching dosage calculation, grounded in research on mathematical success, is
      presented. Strategies for teaching dosage calculation based on this model are
      discussed.

PMID- 11984395
TI  - Student nurse stress in the preceptorship experience.
AB  - Student nurses appear to experience significantly more stress during their
      academic preparation than they do during the first year of employment.
      Preceptorship is among the most stressful of student experiences. It is within
      the context of a challenging and at times daunting work environment that two
      complete strangers (preceptor and student) strive to accommodate one another
      within a professional capacity. If the relationship between preceptor and student
      is less than successful, not only can it be frustrating and disheartening, but it
      can result in student stress and disillusionment about nursing and an inability
      to integrate and learn. Using a hypothetical case, the authors discuss the
      importance of student assessment, close communication between faculty and
      preceptors, and quick responses to student stress as a means by which to
      circumvent the serious potential of student burnout in the practice setting.

PMID- 11984396
TI  - Teaching students to care for and about people with disabilities.
AB  - Although nursing curricula emphasize acute care in hospitals and communities, 25%
      of North Americans are living with long-term disabilities without an available or
      foreseeable cure. Underserved in our society, this group is also underserved in
      nursing curricula, which rarely address their unique needs and issues. The
      authors share information about a required baccalaureate nursing course focusing
      on people with disabilities and the changes in students who complete the course.

PMID- 11984412
TI  - 'Unruffling' the mystique of therapeutic touch. A voice for TT.

PMID- 11984397
TI  - Do progression and remediation policies improve NCLEX-RN pass rates?
AB  - Administrators at 5 schools of nursing who implemented a progression policy based
      on HESI Exit Exam scores were interviewed regarding their NCLEX-RN pass rates
      before and after initiating the policy and methods used for remediation. Even
      though the methods used for remediation were quite different among the
      participating schools, data obtained from these interviews indicated that the
      schools' NCLEX-RN pass rates improved 9-41% within 2 years after implementing the
      progression policies.

PMID- 11984413
TI  - 'Unruffling' the mystique of therapeutic touch. And voices against TT.

PMID- 11984414
TI  - Debate or deceit? A look at CRNA care.

PMID- 11984415
TI  - Prevent corticosteroid-induced osteoporosis.

PMID- 11984416
TI  - Where do leukotriene modifiers fit in asthma management?
AB  - Effective asthma treatment requires long-term inflammation control. Patient
      adherence to corticosteroid treatment regimens remains problematic. Leukotriene
      modifiers, a newer drug class, add to the pharmacologic approaches to asthma
      management. Here, we review the role of leukotrienes in asthma pathogenesis and
      appropriate uses for leukotriene modifiers in asthma management.

PMID- 11984417
TI  - Chronic hepatitis C: latest treatment options.
AB  - The most common chronic bloodborne infection in the United States, hepatitis C
      virus (HCV) is the most frequent reason for liver transplantation. Unfortunately,
      most infected individuals don't realize they're HCV positive and only discover
      the disease after severe liver damage has occurred. Here, update your knowledge
      on the epidemiology, transmission and risk factors, diagnosis, clinical
      presentation, and management of chronic HCV. Insight on counseling and quality of
      life issues for infected patients is also included.

PMID- 11984418
TI  - Should you recommend a low-carb, high-protein diet?
AB  - Despite the billions of dollars spent each year on weight-loss diets and
      products, few individuals maintain their weight loss after initiating popular
      diet programs. One diet that has raised safety concerns among the scientific
      community is the low-carbohydrate, high-protein diet. This article evaluates the
      scientific validity of this diet so that clinicians can appropriately advise
      patients.

PMID- 11984419
TI  - The long and winding road to NP unity.

PMID- 11984421
TI  - PREVENTIVE CARE.

PMID- 11984420
TI  - Using anakinra for adult rheumatoid arthritis.

PMID- 11984422
TI  - CARDIOVASCULAR CARE.

PMID- 11984423
TI  - Clinical Tips: The New Commission on Dietetic Registration/Professional
      Development Portfolio Process: You're in the Driver's Seat.
AB  - After more than 25 years of credentialing dietetic professionals, the Commission
      on Dietetic Registration is revising the format for logging continuing
      professional education. As of 2001, the new system will be phased in over 5
      years. Each registered dietetic professional will now plan a course of continuing
      education to meet personal and professional growth needs. This is a very exciting
      process and one that has many asking questions of "why, how, when, and where."
      This article is designed to put a perspective on the new process.

PMID- 11984424
TI  - Food and Nutrition Policy: Food, Nutrition, Germs, and Health: The 2001 Hazel K.
      Stiebeling Lecture.
AB  - Safe food is a prerequisite for good nutrition and health. This idea has driven
      scientific investigations and public policies that, in turn, led to major
      improvements in health and longevity. Changes in food production and consumption
      practices, population demographics, and health status and understanding the long
      term health consequences of food-borne illnesses will impel future policy
      reforms.

PMID- 11984425
TI  - Guest Editorial: Managing Bovine Spongiform Encephalopathy Risk in the United
      States.
AB  - The United States has built a triple firewall system to prevent the introduction
      or emergence of bovine spongiform encephalopathy. The firewalls are preventing
      bovine spongiform encephalopathy's introduction through bans on imports of
      animals and animal products, actively looking for bovine spongiform
      encephalopathy in the US cattle herd, and banning ruminant animal feed
      supplements found to carry the infectious agent and spread the disease in
      England.

PMID- 11984427
TI  - Editorial Advisory Board Spotlight: CATHERINE WOTEKI, PhD.

PMID- 11984426
TI  - Food Safety: Bovine Spongiform Encephalopathy (Mad Cow Disease).
AB  - Bovine spongiform encephalopathy is just one of a group of diseases known as
      transmissible spongiform encephalopathies. Only recently has it become recognized
      that transmissible spongiform encephalopathies are likely due to proteins known
      as prions. Although it has been recognized that transmissible spongiform
      encephalopathies may readily spread within species, the recent observations that
      bovine spongiform encephalopathy in cattle may have originated from another
      transmissible spongiform encephalopathy in sheep, known as scrapie, is cause for
      concern. Further, bovine spongiform encephalopathy has now been strongly linked
      with a universally fatal human neurologic disease known as new variant
      Creutzfeldt-Jakob disease. Currently the only approach to preventing bovine
      spongiform encephalopathy, and subsequent new variant Creutzfeldt-Jakob disease
      in humans, from ingestion of bovine spongiform encephalopathy-infected material
      is to avoid consumption of contaminated food. Little can be done to treat food
      that will destroy prions and leave a palatable product. At this stage we are
      continuing to learn about transmissible spongiform encephalopathies and their
      implications on human health. This is an ever-changing situation and has an
      unpredictable element in terms of the extent of the current outbreaks in England
      and other parts of Europe.

PMID- 11984428
TI  - In Summary: Caffeine for the Sustainment of Mental Task Performance: Formulations
      for Military Operations.

PMID- 11984429
TI  - Focus on Communications: Communicating the Message: Clarifying the Controversies
      About Caffeine.
AB  - Today's "coffee culture" and the widespread availability of caffeine-containing
      foods and beverages fuel the ongoing study of caffeine and its subsequent
      coverage by the media. Although the media has become influential in communicating
      health and nutrition information to the public, coverage of emerging science,
      such as the study of caffeine, does not necessarily bring clarity or improved
      understanding for consumers. This article highlights the current knowledge of
      caffeine's effects on health, with emphasis on the most common areas of interest
      and confusion. To address persistent misperceptions about caffeine, this article
      also accentuates the need for nutrition professionals to help put the findings of
      caffeine research into perspective and suggests practical ways to do this.

PMID- 11984431
TI  - Business and Nutrition: Our Ready-prepared Ready-to-eat Nation.
AB  - Ready-to-eat/ready-prepared foods loom larger in most Americans' eating
      repertoires than they realize. One of our nutrition-business experts takes a look
      at how we got there and what is likely next.

PMID- 11984432
TI  - Are Activity and Diet Really Important for Children's Bones?
AB  - During the last decade the focus of osteoporosis prevention moved toward
      understanding the importance of maximizing peak bone mass early in life. The role
      of nutrition, physical activity, and genetics in the attainment of peak bone mass
      is currently a major focus of osteoporosis research. Calcium intake and physical
      activity play important roles in the development of peak bone mass. Genetics also
      plays an important role and may interact with diet and activity in its effect on
      bone. Future studies on how diet, activity, and genetics interact with each other
      will provide important insights into the development of peak bone mass.

PMID- 11984433
TI  - What Do Infants Really Eat?
AB  - This article compares the feeding practices of healthy infants reported by their
      mothers in studies spanning two decades. Nutrient intakes are largely adequate
      and feeding practices are changing to meet recommendations, but breast-feeding
      rates do not meet public health guidelines.

PMID- 11984434
TI  - Weight Loss and Medication in Polycystic Ovary Syndrome Therapy.
AB  - Polycystic ovary syndrome, which is a complex syndrome, affects approximately 6%
      of reproductive-age women. Many abnormalities are associated with polycystic
      ovary syndrome, but confusion still exists about their causation. Diagnosis of
      polycystic ovary syndrome is by exclusion. Management of the metabolic aspects of
      polycystic ovary syndrome focuses on minimizing insulin resistance and
      hyperinsulinemia with diet therapy or insulin-lowering drugs.

PMID- 11984435
TI  - Diet and Polycystic Ovary Syndrome.
AB  - Polycystic ovary syndrome is a common endocrine disorder found in up to 10% of
      women. It can have profound metabolic consequences, including increased risk of
      diabetes and heart disease, if not treated. The majority of women with polycystic
      ovary syndrome are obese and many are insulin resistant. Diet, exercise, and
      weight loss play important roles in the treatment of polycystic ovary syndrome.

PMID- 11984436
TI  - The Nutrition Status of Women and Children Who Are Homeless.
AB  - Women and children are the fastest growing segment of the homeless population,
      and yet there is a lack of research examining their nutrition status. This
      article reviews existing literature to understand better their situation and what
      might be effective strategies to improve their condition.

PMID- 11984437
TI  - Editorial Advisory Board Spotlight.

PMID- 11984438
TI  - Food Brands: Friend or Foe?
AB  - Food brands are household words to many Americans but some are anathema to
      nutritionists and they would gladly banish them. Here's a look at the pros and
      cons of some of the old favorites from our nutrition business editor.

PMID- 11984439
TI  - The Emerging Roles of Zinc in Infant Nutrition, Development, and Infectious
      Diseases: Part 2.
AB  - This part of the series on zinc delineates current knowledge on the roles of zinc
      in immunity and infectious disease. It also suggests strategies for improving
      zinc status.

PMID- 11984440
TI  - Epidemic Lymphogranuloma venereum during epidemics of crack cocaine use and HIV
      infection in the Bahamas.
AB  - BACKGROUND: Since the early 1980s, the Bahamas has experienced sequential
      epidemics of freebase/crack cocaine use, genital ulcer-inguinal adenopathy
      disease (GUD), and heterosexual HIV infection. GOAL: To prospectively define the
      etiology of GUD in patients at the Princess Margaret Hospital during outbreaks of
      crack cocaine use, GUD, and HIV infection in the Bahamas. STUDY DESIGN: In
      Nassau, 47 consecutive patients with GUD underwent serologic testing for syphilis
      and for infections with HIV, herpes simplex virus type 2 (HSV-2), and Chlamydia
      trachomatis. Genital ulcer specimens were tested by culture and/or polymerase
      chain reaction (PCR) assay for Haemophilus ducreyi; by PCR and/or antigen assay
      for HSV; and by PCR for C trachomatis. Lymph node aspirates were tested by PCR
      for C trachomatis and H ducreyi. RESULTS: Twenty patients (43%) had HIV
      infection; eight had lymphogranuloma venereum (LGV), confirmed by PCR detection
      of C trachomatis sequences consistent with the L2 serovar; and nine others had
      possible LGV, on the basis of serum microimmunofluorescent C trachomatis antibody
      titers > or =256. Inguinal lymphadenopathy or bubo was present in 15 of 17
      patients, who thus met the laboratory criteria for definite or possible LGV, and
      in 7 of 30 who did not meet such laboratory criteria (P < 0.001). Thirteen
      patients had confirmed genital herpes, seven had confirmed chancroid, and four
      had probable or possible primary syphilis. CONCLUSIONS: The epidemics in the
      Bahamas of crack use, heterosexual HIV infection, and GUD apparently included
      epidemic transmission of LGV.

PMID- 11984441
TI  - Epidemic crack cocaine use linked with epidemics of genital ulcer disease and
      heterosexual HIV infection in the Bahamas: evidence of impact of prevention and
      control measures.
AB  - BACKGROUND: Epidemic freebase/crack cocaine use began in the Bahamas in 1982,
      closely followed by epidemics of genital ulcer disease (GUD) and HIV infection.
      Numbers of new clients receiving ambulatory treatment for cocaine use in Nassau
      peaked in 1984. GOAL: To assess interrelations among epidemics of crack use, GUD,
      and HIV infection. STUDY DESIGN: The study was designed for review and comparison
      of temporal trends in ambulatory and inpatient treatment of cocaine users and in
      numbers of cases of sexually transmitted disease (STD) and HIV infection in the
      Bahamas. A retrospective case-control study of cocaine use and STDs was performed
      at the Comprehensive Dermatovenereology Clinic in Nassau. RESULTS: Ambulatory
      visits and inpatient admissions for cocaine use peaked in 1984 and 1987,
      respectively. GUD cases increased 12-fold in the Bahamas from 1983 to the period
      of 1985-1987 and then declined. At the Comprehensive Dermatovenereology Clinic,
      gonorrhea cases outnumbered bacterial GUD cases approximately 10:1 in 1982 and
      1983, but the latter increased to outnumber gonorrhea cases in 1985 and 1987
      1988. Annual HIV seroprevalences at new-problem visits rose from less than 0.3%
      in 1986 to 12.9% by 1994 and then leveled off. Cocaine use among patients seen
      with STD from 1985 through 1990 was significantly associated with GUD (odds ratio
      [OR], 3.3; 95% CI, 2.1-5.1), secondary syphilis (OR 5.5; 95% CI, 2.4-12.6), and
      HIV infection (OR, 8.1; 95% CI, 4.3-15.2). CONCLUSIONS: In temporally linked
      successive epidemics of cocaine use, GUD, and HIV infection, case-control
      analyses confirmed the association of cocaine use with GUD and with HIV
      infection. Declining GUD and HIV seroprevalence stabilization followed declines
      in cocaine use and implementation of syndromic management of GUD, as well as
      intensified partner-notification efforts.

PMID- 11984442
TI  - Human immunodeficiency virus and other sexually transmitted infections among
      female sex workers in two major cities in Papua New Guinea.
AB  - BACKGROUND: Treatable sexually transmitted infections are very common in
      developing countries and quite often are inadequately treated or remain untreated
      despite the fact that they enhance the transmission of human immunodeficiency
      virus (HIV). GOAL: To estimate the prevalence of HIV, syphilis, chlamydial
      infection, gonorrhea, and trichomoniasis among female sex workers in Port Moresby
      and Lae, Papua New Guinea, and to collect data on associated behaviors. STUDY
      DESIGN: Self-identified female sex workers recruited through our peer-mediated
      sexually transmitted disease (STD)/HIV risk-reduction community outreach program
      were invited to participate in the study. Participants underwent pretest
      counseling, were interviewed, and were asked to self-collect vaginal swab
      specimens for the detection of STDs and to provide 10 mL of blood for HIV and
      syphilis testing. RESULTS: A total of 407 female sex workers, 207 in Port Moresby
      and 200 in Lae, were enrolled in the study. The overall prevalence rates of HIV,
      syphilis, genital chlamydial infection, gonorrhea, and trichomoniasis among these
      women were estimated to be 10%, 32%, 31%, 36%, and 33%, respectively. The sex
      workers in Port Moresby had a significantly higher HIV infection rate (17%) than
      those in Lae (3%) and a significantly lower trichomoniasis rate (21%) than those
      in Lae (44%). Mixed infections were common, occurring in 45% of the cases.
      Despite a high rate of symptoms, the rate of treatment-seeking was low. Condom
      use among the sex workers was very inconsistent; 85% reported that they did not
      use condoms at all times when having sex with their clients. Common reasons cited
      were dislike by clients, unavailability, alcohol use, and familiarity with a
      client. CONCLUSIONS: STDs are very common among female sex workers in Port
      Moresby and Lae and very often present as multiple infections. Despite STD/HIV
      awareness campaigns, unsafe sex-particularly irregular use of condoms-continues
      among sex workers and their clients. Barriers to safer sexual behavior need to be
      addressed, as do improvements in provision of STD services.

PMID- 11984443
TI  - Screening women in jails for chlamydial and gonococcal infection using urine
      tests: feasibility, acceptability, prevalence, and treatment rates.
AB  - BACKGROUND: Women entering jails are at high risk for sexually transmitted
      diseases; however, screening for chlamydial and gonococcal infection is not
      routinely performed in most jails. New urine tests have made it easier to screen
      for these infections in nonclinical settings. GOAL: The feasibility and
      acceptability of urine-based screening for women entering jails and the
      prevalence of and treatment rates for chlamydial and gonococcal infections were
      determined. STUDY DESIGN: Women entering jails in Chicago, Illinois; Birmingham,
      Alabama; and Baltimore, Maryland, who signed consent forms were tested for
      chlamydial and gonococcal infection by means of the urine ligase chain reaction
      assay. Those testing positive were treated in jail; health department staff
      members attempted to contact those already released. RESULTS: Most women who were
      approached agreed to be tested (range, 87-98%, depending on city), and most of
      these women provided a specimen (range, 92-100%). Among 5364 women aged 16 to 75
      years who were tested, the prevalence of chlamydial and gonococcal infections was
      high, especially among those <25 years of age (range, 15.3-21.5% for chlamydial
      infection and 8.2-9.2% for gonorrhea, depending on city). The majority of women
      testing positive were treated in jail or outside of jail (61-85%). CONCLUSIONS:
      Screening women in jails for chlamydial and gonococcal infection with urine tests
      is feasible, is acceptable to most women, and leads to detection and treatment of
      many infections. Routine screening should reduce medical complications in this
      population and should prevent transmission in the community, given that many
      women are soon released.

PMID- 11984444
TI  - Rapid public health interventions in response to an outbreak of syphilis in Los
      Angeles.
AB  - BACKGROUND: Despite national ambitions to eliminate syphilis, occasional
      outbreaks continue to occur in many areas of the United States. GOAL: The goal of
      the study was to describe and evaluate the public health interventions in
      response to an outbreak of syphilis in Los Angeles County among men who have sex
      with men. STUDY DESIGN: Reported cases of primary, secondary, and early latent
      syphilis that occurred during an outbreak period from December 1999 to September
      2000 were included in the study. The outbreak components of provider awareness,
      active surveillance, community-based organization recruitment, media campaign,
      community-outreach education and screening, and a correctional facility
      intervention were described. Screening results were reviewed, sexually
      transmitted disease (STD) hotline calls were counted, and a street-intercept
      survey was conducted. RESULTS: A multifaceted outbreak response was initiated in
      March 2000. Of the 89 outbreak cases identified, 40% were detected by HIV/AIDS
      early intervention providers and 26% by private clinicians or health maintenance
      organizations. Other case identification sources included public STD clinics
      (10%), STD program case-management contacts (7%), mobile van screening (7%), and
      correctional facility screening (10%). Screening at high-risk venues detected a
      syphilis prevalence of <1% and an HIV prevalence of 6%. Weekly calls to the STD
      hotline increased 600% during the outbreak, and 80% of surveyed individuals cited
      the media as the source of their awareness of syphilis. CONCLUSIONS: A
      multifaceted outbreak response was launched to react to an outbreak of syphilis
      among men who have sex with men. Prompt provider awareness and a preexisting
      network of HIV/AIDS providers aided case detection. Although the effectiveness of
      the response could not be scientifically determined, the diverse components of
      the response were associated with a faster decline in the outbreak than would
      have been expected. After 3 months, 89 cases had been identified. Outbreak
      preparedness should include a focus on communities of men who have sex with men,
      because the reintroduction of syphilis in this population may threaten national
      efforts toward syphilis elimination.

PMID- 11984445
TI  - Syphilis outbreaks among men who have sex with men: a public health trend of
      concern.

PMID- 11984446
TI  - Microflora changes with the use of a vaginal microbicide.
AB  - BACKGROUND: The rate of HIV transmission is increasing more in women than in any
      other group. There is an urgent need for the development of microbicides with
      activity against this virus that women can use during intercourse. These products
      must be convenient, effective, and safe, and ideally they will cause minimal
      disruption in the normal vaginal ecosystem. GOAL: The objective of this study was
      to evaluate changes in vaginal microflora, specifically Lactobacillus species,
      with the use of BufferGel. STUDY DESIGN: A prospective cohort study was performed
      to evaluate the change in vaginal flora before and after BufferGel use. BufferGel
      was applied vaginally once or twice daily for 14 days by low-risk abstinent and
      monogamous women. RESULTS: There was no change in frequency of Lactobacillus
      species after BufferGel use. However, there was a decrease in H2O2-producing
      lactobacilli (from 4.9 x 107 to 1.1 x 107 cfu; P = 0.001). The proportion of
      facultative gram-negative rods present increased from 27% to 65% after BufferGel
      use, whereas obligately anaerobic microbes decreased from 62% to 38%. CONCLUSION:
      Use of BufferGel once or twice daily for 14 days resulted in no clinically
      significant change in Lactobacillus colonization.

PMID- 11984447
TI  - Community-based chlamydia and gonorrhea screening through the United States mail,
      San Francisco.
AB  - BACKGROUND: Because gonococcal and chlamydial infections are often asymptomatic,
      disease control requires population-based screening. This report describes the
      feasibility of home-based testing for sexually transmitted diseases (STDs) and of
      specimen transport via the US mail. GOAL: This project sought to establish the
      efficacy and acceptability to the public of screening by means of urine kits made
      available in public places and mailed in for STD testing. STUDY DESIGN: Self
      selected community participants obtained STD test kits from local businesses,
      collected urine specimens at home, and mailed kits to the health department for
      nucleic acid amplification testing. RESULTS: Participants picked up 209 test kits
      and returned 80 (38%): 3 (3.8%) of 76 were positive for gonorrhea and 1 (1.3%) of
      76 was positive for chlamydia. The majority (95%) of participants were white gay
      men. The cost of specimen collection and transport was similar to that of other
      population-based screening programs. CONCLUSION: Using the mail for home-based
      testing for gonorrhea and chlamydia was feasible and may be a useful addition to
      STD control efforts.

PMID- 11984448
TI  - Using sexually transmitted disease incidence as a surrogate marker for HIV
      incidence in prevention trials: a modeling study.
AB  - BACKGROUND: Because many of the sexual behaviors that place individuals at risk
      of acquiring HIV are the same as those that place them at risk for other sexually
      transmitted diseases (STDs), researchers and policymakers have called for the use
      of non-HIV STDs as surrogate markers for HIV infection. GOALS: This study
      examined the epidemiologic conditions under which changes in STD incidence are
      associated with changes in HIV incidence. STUDY DESIGN: A mathematical model of
      HIV/STD transmission was applied to empirical data from a large HIV prevention
      intervention. The association between participants' HIV infection risk reduction
      scores and their STD risk reduction scores was measured with use of the Pearson
      product-moment correlation. The authors examined how the strength of association
      varied across different epidemiologic parameters and heterosexual behaviors.
      RESULTS: Moderate to strong associations were noted when the infectivity of the
      STD was similar to the infectivity of HIV. The association was attenuated for
      larger STD infectivity values. The prevalence of STD infection was a less
      important determinant of the strength of association. Stronger associations were
      obtained when the number of sex partners was large or the number of sex acts was
      small. CONCLUSIONS: Easily transmitted STDs, such as gonorrhea, are unsuitable
      for general use as surrogate markers for HIV infection. Hepatitis B, syphilis,
      and chlamydial infection have more promising epidemiologic profiles. Careful
      studies of STD infectivity are needed to aid in the identification of potential
      marker STDs.

PMID- 11984449
TI  - In vitro reactivation of HIV-1 by stimulation with herpes simplex virus
      infection.

PMID- 11984451
TI  - Health professionals keep making the same mistakes.

PMID- 11984452
TI  - Nurse who failed to account properly for residents' money.

PMID- 11984454
TI  - Patients need a well educated and rewarded nursing workforce.

PMID- 11984453
TI  - Nurses of all levels can improve patients' experience of health care.

PMID- 11984455
TI  - Sixty-five years of nursing: selected recollections.

PMID- 11984456
TI  - Generating dialogue in nursing.

PMID- 11984457
TI  - Nutritional care: implications and recommendations for nursing.
AB  - Nutrition is a basic human requirement with both physiological and psychosocial
      dimensions that affect well-being. In times of illness ensuring adequate
      nutrition is particularly important because of the central part it plays in
      healing and recovery. This article explores the premise that current nutritional
      care in nursing practice is often inadequate with the result that patients'
      nutritional requirements are not met. It investigates the causative factors of
      poor nutritional care in nursing practice, the implications of such practice for
      both the patient and the professional, and proposes a number of recommendations
      for future change.

PMID- 11984458
TI  - Lymphoedema 3: the available treatments for lymphoedema.
AB  - The third article in this series describes the treatment available to sufferers
      of lymphoedema in the UK. Lymphoedema is a condition that cannot be cured and
      requires lifelong treatment to control symptoms that, if left untreated, would
      progressively worsen. The aim of treatment is to stabilize the oedema and empower
      the patient with the necessary skills to undertake self-care. Four components of
      treatment are used to achieve this goal: care of the skin, compression and
      support, lymphatic massage and exercise. The purpose of each treatment will be
      explained and supported with research findings. Examination of the literature
      reveals a weak evidence base supporting treatment practice in this country. The
      majority of evidence relates to vascular insufficiency and findings from abroad.
      A brief account will be made of the reasons for this and how the trend is
      changing.

PMID- 11984459
TI  - Contractual responsibilities of both the employer and employee.

PMID- 11984460
TI  - Myocardial infarction: nursing responsibilities in the first hour.
AB  - The aim of this article is to provide a comprehensive review of the physiological
      processes that occur during the first hour following a myocardial infarction
      (MI). It will identify the general principles and the physiological processes
      that occur in response to a MI, outlining the consequences of cellular hypoxia to
      the heart. The implications for clinical practice and how they link to the
      physiological processes are detailed. Understanding the physiological principles
      involved in a MI is important for identification and to ensure patient management
      is initiated. This, together with prompt diagnosis and interventions, will assist
      in reducing mortality within the first hour following a MI.

PMID- 11984461
TI  - National Service Framework for Older People: promoting health.
AB  - In March 2001, the National Service Framework (NSF) for Older People set out
      standards for the care and treatment of the over 60s in England. In Wales, a
      strategy for older people is expected in 2002. The eight standards of the NSF for
      Older People include strategies to reduce falls, strokes and poor mental health
      among older people as well as improving general and intermediate care. The final
      standard "Promoting health and active life in older age" is an overarching theme.
      As well as strategies to promote health in older people, the NSF requires service
      providers to develop long-term strategies to promote health throughout life in
      order to prevent chronic illness. This should include the prevention and
      treatment of osteoporosis. In promoting positive role models, the NSF for Older
      People is reflecting social trends in tackling ambivalence about ageing. Key
      themes of the standard include empowerment and improving quality of life for
      older people. Patient-centred care and the appointment of older people's
      champions are possible routes towards this aim. Although there is evidence of
      some patient-focused models of health promotion, a review of the literature
      suggests that these are limited.

PMID- 11984462
TI  - Nurses' views about returning to practice after a career break.
AB  - Shortages in nursing staff have led to recruitment campaigns targeting nurses who
      have left the profession. The present study explored reasons why career-break
      nurses decide for or against a return to practice, as well as perceptions of
      nursing following return. Semistructured interview were conducted with 24 nurses
      who had returned recently to the profession and 28 nurses on a "career break".
      Findings revealed that those who returned did so when their personal
      circumstances allowed, and half returned as bank nurses in order to work
      flexible, family-friendly hours. Some non-returners reported that they could not
      afford to return because of childcare costs. Although still a caring one, the
      nurse's role is seen by returners as becoming increasingly technologically and
      administratively demanding. Flexibility with regard to working practices,
      increased salaries and demonstrating that it values its staff, were highlighted
      by interviewees generally as priority issues for the NHS if it wishes to recruit
      career-break nurses.

PMID- 11984463
TI  - Review of advances in pressure ulcer management since 1992.
AB  - This article seeks to review the progress in the treatment and prevention of
      pressure ulcers over the last 10 years under the headings of attitudes, politics,
      research and best practice. It is considered that attitudes have changed and
      there is a greater awareness of, and interest in, the topic among other
      healthcare professionals, not just nurses. This may be in part because the topic
      has risen up the political agenda following studies that have highlighted the
      numbers of sufferers and the cost of treatment. Unfortunately, there is a
      scarcity of high quality research to inform practice. Despite these limitations,
      overall, there has been some progress in preventing and treating pressure ulcers,
      but there is still a considerable journey ahead.

PMID- 11984464
TI  - A review of children's nursing: but does it have a future?
AB  - With less than 35,000 registered children's nurses in the UK it is timely in the
      10-year anniversary issue of the British Journal of Nursing to examine the
      progress of children's nursing. This article explores the ramifications of the
      outgoing UKCC's 'Fitness for Practice and Purpose' document (UKCC, 2001) and its
      legacy to the incoming Nursing and Midwifery Council. The argument as to whether
      preregistration nurse training should become generic with specialization
      occurring as a postregistration activity will be debated.

PMID- 11984465
TI  - Developments in learning disability nursing over the last 10 years.
AB  - This article aims to reflect upon the changes in the learning disability nursing
      profession over the last 10 years. It highlights the nurses' role in supporting a
      change of culture within the field of learning disability from one of oppression
      and restriction of individual rights to one where the principles characterized in
      the White Paper--civil rights, independence, choice and inclusion--are being
      increasingly supported by learning disability nurses. It concludes by examining
      the key issues that face the learning disability profession over the next 10
      years.

PMID- 11984466
TI  - Working with older people: what do the next 10 years hold?
AB  - This article briefly considers the challenges facing gerontological nursing over
      the next 10 years. It suggests that future quality of care will depend largely on
      the ability to recruit and retain staff who actively choose to work with older
      people. This will mean raising the status and profile of gerontological nursing
      and identifying a philosophy that provides direction and purpose for future care
      practices.

PMID- 11984467
TI  - An examination of the last 10 years of mental health nursing.
AB  - This article offers an examination of the mental health nursing articles
      published in the British Journal of Nursing during the last 10 years, and a
      commentary on how these reflect developments within this specialism. It
      identifies a number of clinical and professional issues, which have emerged over
      the last decade, including: community care; concerns over the quality of acute
      inpatient services; clinical supervision; and the integration of schools of
      nursing into higher education. Finally, the article identifies some clinical
      areas which it suggests warrant attention in the next decade such as child and
      adolescent mental health and mental health care for older people.

PMID- 11984468
TI  - The development of the role of the clinical nurse specialist in the UK.
AB  - The modern development of specialist nurses started in the early 1970s. This
      article provides a brief history of their evolution and in particular outlines
      some of the key factors in their emergence as a key care provider in health care
      today. There is a constant threat that their clinical nursing background and key
      nursing skills will be sacrificed or substituted by a more medical-oriented
      approach. The future, therefore, is one of striking the right balance between
      nursing and medicine sub-specialism and holistic patient care.

PMID- 11984469
TI  - Introducing the Reflexion pressure-redistributing cushion.
AB  - Preventing pressure ulcer incidence and ensuring patient comfort are essential
      components of providing quality clinical care (Hampton, 2001), and therefore
      comfortable pressure-redistributing seating should be a prerequisite to care
      provision. However, even though education in tissue viability has increased, it
      is only within the last 2 years that chair cushions have been noted for their
      importance in reducing pressure ulceration. It is not unknown for patients to
      have excellent pressure-reducing equipment on the bed but have chair cushions
      that are of an inferior standard (Hampton, 1999). This article, therefore,
      examines the Reflexion cushion, manufactured by Vitafoam, and the role it may
      have in preventing pressure ulceration.

PMID- 11984470
TI  - 10 years on and I fear for the future of nursing.

PMID- 11984471
TI  - [The Journal of Neuroradiology moves ahead].

PMID- 11984472
TI  - DWI prediction of symptomatic hemorrhagic transformation in acute MCA infarct.
AB  - PURPOSE: Symptomatic hemorrhagic transformation is a severe complication of acute
      ischemic stroke which occurs at a higher frequency after thrombolysis. The
      present study was designed to analyze whether early DWI can be used for
      predicting the risk of hemorrhagic transformation with clinical worsening in MCA
      stroke patients. MATERIALS AND METHODS: Of 28 patients with a middle cerebral
      artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MR
      angiography performed within 14 hours after onset (mean 6.5 +/- 3.5 hours, median
      5.2 hours), 4 developed hemorrhagic transformation with clinical worsening, while
      24 did not. For the 2 groups, we compared admission NIHSS score, site of arterial
      occlusion, volume of DWI abnormalities, and several apparent diffusion
      coefficient (ADC) measurements: ADC(infarct) (mean ADC value of the whole
      infarct), ADC(core) (peak ADC decrease as calculated in a 57 mm(2) circular ROI,
      manually centered on the ischemic area with the lowest ADC value on the ADC
      maps), ADC(superficial) and ADC(deep). Discriminant function analysis was used to
      determine the most accurate predictors of symptomatic hemorrhagic transformation.
      RESULTS: The best predictor was the ADC(core) (F=5.34, p=2.9%, cut-off value=300
      x 10(-6) mm(2)/s). This monovariate model allowed to correctly classify all 4
      patients (ADC(core) 300 x 10(-6) mm(2)/s) with subsequent symptomatic hemorrhage,
      and 17 of the 24 patients without symptomatic hemmorrhage (ADC(core)>300 x 10(-6)
      mm(2)/s) (100% sensitivity, 71% specificity). CONCLUSION: Although preliminary,
      these results suggest that a simple measurement of minimum ADC values within an
      acute MCA stroke could be useful in targeting those patients with a high risk of
      severe hemorrhagic transformation.

PMID- 11984473
TI  - [MRI: an essential examen for the management of sacrococcygeal chondromas].
AB  - Chordomas are rare tumors, involving mainly the sacrococcygeal area and the
      clivus. Although a significant radiological semiology exists (osteolytic,
      lobulated, calcified tumor), the definite diagnosis is histological. Five cases
      of sacral and/or coccygeal chordomas were studied by CT scan and MRI. Clinical,
      radiological (tumoral topography and extension) and histological data were noted
      in all cases. At CT scan, the tumor was median, osteolytic, often calcified, of
      intermediate density, sparing iliac bones. MRI showed, in all the cases, a
      tumoral lobulation making easier the diagnosis of chordoma. Futhermore, as
      compared to CT scan MRI brought new information for the study of the tumoral
      extension, revealing a frequent involvement of adjacent muscles and spinal canal.
      It also showed that the tumor most often spared the rectal wall. These data are
      fundamental in the management of patients: the therapeutical aim must be, if
      possible, a complete removal of the tumor. Thus, besides its interest in the
      diagnosis, MRI appears to be essential in the pre-therapeutical assessment of
      sacro-coccygeal chordomas.

PMID- 11984474
TI  - Proton MR spectroscopy in the diagnosis and differentiation of encephalitis from
      other mimicking lesions.
AB  - In this study, proton magnetic resonance spectroscopy (1H MRS) findings of
      encephalitis were reported. For comparison, other lesions mimicking encephalitis
      on conventional magnetic resonance (MR) imaging were included in the study. These
      lesions consisted of acute infarctions and low grade infiltrative gliomas. The 1H
      MRS findings of encephalitis and gliomas were almost the same whereas infarctions
      revealed high lactate levels differentiating the disorder from other two
      pathologies. The differentiation of encephalitis and gliomas based on MR findings
      could reliably made with short time follow up MR examinations where gliomas tend
      to grow in contrast to encephalitis which showed regression.

PMID- 11984475
TI  - Morphometric comparison of the human corpus callosum in professional musicians
      and non-musicians by using in vivo magnetic resonance imaging.
AB  - The purpose of this study was to determine the possible morphometrical
      differences of the corpus callosum between professional musicians and non
      musicians. Certain callosal dimensions and areas were measured in 20 professional
      musicians and compared with 20 age-, sex- and handedness-matched control group by
      using in vivo magnetic resonance imaging (MRI). Sagittal T1-weighted midsagittal
      sections were traced with the digitizer and the metric scale of the system was
      used for the measurements. Results were statistically analysed by independent t
      test. There were significant differences between the two groups both for the
      anterior and posterior areas of the corpus callosum. Furthermore, significant
      differences between the two groups were found in the thicknesses of certain parts
      of the corpus callosum. Our results support the hypothesis that brain morphology
      is prone to plastic changes caused by environmental factors.

PMID- 11984476
TI  - [What is your diagnostic? Pseudotumoral cerebral actinomycosis].

PMID- 11984477
TI  - Diffusion-weighted imaging in a case of wernicke encephalopathy.
AB  - In a chronic alcoholic patient with progressive confusion, which was consistent
      with the clinical diagnosis of Wernicke encephalopathy, T2-weighted, FLAIR and
      diffusion weighted (DWI) MR imaging depicted brain abnormalities located in both
      medial thalamic nuclei. Apparent Diffusion Coefficient (ADC) measurements in
      these regions shown unexpected normal values, referring to Wernicke pathological
      findings and DWI data. DWI may be helpful to diagnose early basal nuclei
      abnormalities, but may fail to compute ADC values in these locations.

PMID- 11984478
TI  - [Idiopathic granulomatous hypophysitis: clinical apppearance and imaging].
AB  - Idiopathic granulomatous hypophysitis is a chronic inflammation of the pituitary
      gland. It is a rare occurrence and is diagnosed only on pathologic examination.
      We report a case of a 23-year-old female patient presenting with polyuria and
      polydipsia associated with a pituitary failure and hyperprolactinemia. MRI study
      showed a space occupying lesion of the pituitary gland with a marked enhancement
      after gadolinium injection. Pituitary biopsy was consistent with the diagnosis of
      idiopathic granulomatous hypophysitis. The aim of this work is to discuss the
      different clinical and radiological aspects of the disease with a special
      emphasis on differential diagnosis.

PMID- 11984479
TI  - [Intracerebral radiation-induced cavernous angiomas].
AB  - We present four cases of cerebral cavernous angioma that developed after
      radiatherapy for brain tumor in three cases and for cavernous angioma in one
      case. The time interval between irradiation and the detection of the cavernous
      angioma varied from three to nine years and the doses from 24 to 60 Grays. Brain
      hemorrhage appeared in two cases. Explanation for the formation of cavernous
      malformations is unclear but is probably related to proliferation and dilatation
      of the vascular endothelium with formation of capillary telangiectasis with
      evolution to cavernous angiomas. The pediatric brain appears particularly
      vulnerable to radiation injury. The risk of hemorrhage appears higher than with
      spontaneous cavernous malformations.

PMID- 11984480
TI  - [Lymphocytic hypophysitis].
AB  - Lymphocytic hypophysitis is a rare inflammatory disease of the pituitary gland
      which may be related to an autoimmune process. Only twenty cases are reported in
      male. Patients usually present with symptoms of an expanding intrasellar mass or
      varying degrees of hypopituitarism. Most of the cases are misconsidered
      preoperatively as pituitary adenomas. We report a case of lymphocytic
      hypophysitis which has occurred at a 37-year-old-man.

PMID- 11984482
TI  - [Gamma knife radiosurgery for the treatment of severe epilepsy].
AB  - The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated
      well its efficiency, its low morbidity and its comfort in the treatment of
      numerous neurosurgical disorders. These advantages of this type of intervention
      make it a method of great interest in functional neurosurgery and quite
      particularly in surgery of epilepsy. French experience is a pionner one in this
      domain. If for several years the positive evolution of the epilepsy associated to
      brain lesions had been noticed after the Gamma Knife radiosurgical treatment, the
      use of this approach in surgery of the epilepsy is systematically estimated since
      1993. Data are today available concerning the surgical treatment of the
      epilepsies originating in temporomesiale area without occupying process,
      epilepsies associated to hypothalamic hamartomas and epilepsies associated to
      cavernous angiomas or to low grade gliomas. The quality of the epileptological
      result obtained in these various indications associated to a very reduced
      morbidity lets suppose that the Gamma Knife radiosurgery could indeed have
      tomorrow a place within the sample group of surgical approaches dedicated to the
      treatment of severe epilepsies. However, a larger number of treated patients and
      a more prolonged follow-up remains necessary to estimate in a more definitive way
      this approach.

PMID- 11984483
TI  - [The varied etiologies of childhood-onset dystonia].
AB  - Dystonia is not uncommon in childhood, and identification of its etiology is an
      ultimate aim in the clinical evaluation of dystonia. Advances in neuroimaging,
      recent identification of gene or loci implicated in dystonic syndromes, and
      characterisation of new pathological entities (creatine deficiency, biotin
      responsive basal ganglia disease) enlarge our understanding of childhood
      dystonia, and expend its diagnosis spectrum. Awareness of the diverse etiologic
      categories of childhood-onset dystonia is necessary to accurate diagnosis
      approach. Clinical examination and cerebral magnetic resonance imaging are the
      keys of this diagnosis approach. Primary dystonia is defined as syndromes in
      which dystonia is the sole phenotypic manifestation (especially no cognitive
      deterioration is observed, and brain MRI is normal); DYT1 dystonia, in which the
      abnormal gene is located on chromosome 9, is the most frequent childhood-onset
      primary dystonia; progressive generalisation of the abnormal movements occur in
      70p.cent of the patients. Dopa - Responsive Dystonia are characterized by marked
      diurnal fluctuations of the dystonic symptoms and by their marked and sustained
      response to dopaminergic therapy; associated parkinsonian signs are usually
      observed later in the course of the disease. Clinical presentation of DRD might
      be atypical (mimicking cerebral palsy or isolated limb pain without diurnal
      fluctuation). DRD is rare, but a trial of L-dopa should be performed on all
      patients with childhood-onset dystonia, lasting at least one month. Secondary
      dystonias or heredodegenerative diseases are the most frequent etiology of
      childhood-onset dystonic syndromes. Among a huge range of heredodegenerative
      disease, those that are amenable to a specific treatment, such as Wilson's
      disease or creatine deficiency, should be particularly investigated. The main
      objective of investigation of dystonia is to identify secondary dystonias or
      heredodegenerative diseases. Further investigations will be performed according
      to the clinical characteristics of the dystonia, to the presence of associated
      neurological or extraneurological symptoms, and according to brain imaging; this
      approach must be discussed for each single patient. The aim of the diagnosis
      strategy is the rapid identification of the etiology of dystonia which will lead
      to accurate treatment and pertinent genetic counselling.

PMID- 11984484
TI  - [Double dissociation between unilateral neglect and anosognosia].
AB  - We report two patients presenting with a subacute right hemisphere stroke. These
      cases demonstrate a double dissociation between unilateral neglect and
      anosognosia for hemiplegia. The first patient suffered from a severe left
      hemiplegia associated with severe and persisting unilateral neglect. He appeared
      fully aware of his motor impairment. The second patient had a severe left
      hemiplegia, without any major sign of unilateral neglect on clinical tests nor on
      behavioural assessment. Nevertheless, he presented a severe and sustained
      anosognosia for hemiplegia. These case reports support the assumption that
      anosognosia and unilateral neglect, although they are frequently associated, may
      rely on independent mechanisms.

PMID- 11984485
TI  - [Perceptual analysis of dysarthria: presentation and validation of a clinical
      scale. Preliminary study].
AB  - Perceptual analysis is widely used in clinical practice to assess motor speech
      disorders such as dysarthria. Unfortunately, there is no standardised tool
      available in French. The purpose of this study was first to develop a perceptual
      rating system modelled after systems currently used in the English literature and
      second to determine its reliability. We evaluated 33 dimensions using a 5-point
      scale. The production of 10 dysarthric patients were rated by 9 clinicians during
      both spontaneous speech and a reading task. Intra judge reliability (at 1-point)
      was about 90 percent, while inter judge reliability was about 80 percent. Ratings
      were comparable for the spontaneous speech and the reading task. Perceptual
      analysis of dysarthria is an easy and reproducible approach that can be used for
      the initial evaluation and for the follow up of dysarthric patients.

PMID- 11984486
TI  - [Influence of general practitioners' personal knowledge on migraine in medical
      attitudes towards their patients suffering from migraine].
AB  - The subjective aspects of the doctor-patient relationship may impact disease
      management methods applied to migraine patients. This prospective study compared
      the medical attitudes of doctors towards migraine headache in relationship to
      their personal sensitivity to this disease. The study concerned data on the
      health care management of migraine headache by 711 general practitioners, 325 of
      whom suffer from migraine headache themselves, 227 who do not suffer from
      migraines, but who have a close family member that does, and 159 who neither
      suffer from migraine headache, nor have anyone close who does. Each doctor filled
      out a medical practice questionnaire concerning this pathology and included one
      migraine patient in the survey. Each patient answered a specific quality of life
      questionnaire. It was shown that doctors suffering from migraine headache
      themselves declared having more migraine patients in their practices than the
      other doctors. Nonetheless, the doctor's sensitivity to migraine headache does
      not seem to have an impact on the diagnosis and therapeutic care of patients;
      diagnosis criteria are the same within the three groups and correspond to
      international headache society criteria. Furthermore, the therapeutic means
      applied, whether acute first or second intention treatment, or long-term
      treatment, do not differ amongst the three groups. Quality of life and patients'
      feelings about medical support were significantly related to the doctor's level
      of sensitivity towards the disease: they were highest amongst patients treated by
      doctors suffering from migraines themselves, and lowest amongst patients treated
      by doctors with no close family members suffering from migraines. Although
      therapeutical attitudes do not vary, the quality of life perceived by patients is
      better when the doctors themselves are concerned by the disease.

PMID- 11984487
TI  - [Acute optic neuritis: clinical and MRI prognostic factors. Study of fifty
      patients].
AB  - The objective of this study was to evaluate the risk of visual outcome after
      acute optic neuritis (ON) in relation to clinical and MRI findings. Fifty cases
      of acute ON within one month were retrospectively studied. MRI with Short Tau
      Inversion Recovery (STIR) sequence of the optic nerve were obtained with a median
      time onset of 9 days after ON. Mean age of patients was 32.8 years, mean initial
      visual acuity was 3/10 and orbital pain was present in 86 percent100 of patients.
      The STIR sequence revealed lesion in 88 percent 100 of acutely symptomatic optic
      nerves. An initial low visual acuity (less than 2/10), the absence of orbital
      pain and involvement of the intracanalicular portion of the optic nerve on STIR
      sequence were statistically correlated with a poorer visual outcome (respectively
      p=0.0041, p=0.035 and p=0.011).

PMID- 11984488
TI  - [Assessment of quality of life for home ventilated patients with Duchenne
      muscular dystrophy].
AB  - A social and psychological survey was conducted for patients with DMD submitted
      to home mechanical ventilation for more than one year. Thirty six were
      tracheostomized and 16 were using non invasive ventilation. Fifty two patients
      were recruited: 36 were tracheostomized and 16 were using non invasive
      ventilation. Mean age was 25 +/- 5 years. In the two groups: 1- the main
      disagreement was air leaking and cutaneous erosions. 2- when present, headache,
      dyspnea, sleep troubles and general fatigue were improved by mechanical
      ventilation. 3- ventilation was considered as improving health but with an
      increasing of dependencies. 4- Majors disappointment are sexual life (70 percent)
      and physical status (40 percent) but patients spent more than half time with
      positive feeling (92 percent). There was no difference between satisfaction
      evaluation and type of ventilation. Home ventilated patients with DMD have
      positive assessment of satisfaction. Despite technical disagreement as air
      leaking, patients feel an improvement of their life and advise other DMD to use
      early home ventilation.

PMID- 11984489
TI  - [Hashimoto's encephalopathy: an anatomicoclinical observation].
AB  - Hashimoto's encephalopathy (HE) is a rare neurological complication of chronic
      lymphocytic thyroiditis. As its clinical presentation is aspecific, other
      etiologies of acute encephalopathy have to be ruled out. We report the case of a
      29-year old woman with neuropsychiatric signs preceding coma, myoclonus and
      epileptic seizures. Clinical and electroencephalographic features were consistent
      with the diagnosis of new variant of Creutzfeldt-Jakob disease. However, high
      titres of antithyroid antibodies in serum directed towards the diagnosis of HE.
      Despite oral steroids, the patient died five months later. Neuropathological
      findings ruled out spongiform encephalopathy and disclosed aspecific activated
      microglia. Our observation suggests that this process could be involved in the
      pathogenesis of HE. Even in the absence of clinical dysthyroidism, HE diagnosis
      has to be suspected in the settings of acute encephalopathy associated with seric
      antithyroid antibodies.

PMID- 11984490
TI  - [Chronic meningitis before diagnosis of celiac disease].
AB  - Neurological complications, mainly cerebellar syndrome, have been associated with
      coeliac disease. We report the first observation of a 56-year-old woman with a
      chronic meningitis revealing coeliac disease. Neuralgia of the trijeminal nerve
      and cerebellar syndrome only appeared seven years after the onset of meningitis.
      MRI examination showed a cerebellar atrophy and a leucoencephalopathy. This case
      report emphasizes the utility of detection of anti-gliadin antibodies for the
      diagnosis of a chronic meningitis.

PMID- 11984491
TI  - [Acute encephalitis complicating acute polyradiculoneuritis].
AB  - We report the case of a 43-year-old man who developed an acute encephalopathy
      after IVIg therapy for AIDP. Imaging studies showed predominantly posterior
      leukoencephalopathy. The signs and symptoms of the encephalopathy completely
      resolved by steroids. Two patients with acute encephalopathy, following IVIg
      therapy, were reported previously in the literature. However, our observation
      differed from them by the presence of a marked pleiocytosis of cephalospinal
      fluid before beginning of IgIV. Two hypothesis may be made: a post-infectious
      meningo-encephalo-AIDP or a complication of IgIV. This side effect, even rare,
      has not to be underestimated.

PMID- 11984492
TI  - [Candida albicans meningoencephalomyeloradiculitis].
AB  - A 25-year-old immunocompetent male heroin addict was admitted for acute confusion
      associated with gait disorders of three month duration. The diagnosis was
      meningoencephalomyeloradiculitis secondary to Candida albicans infection. Outcome
      was good after a 6-month regimen with antifungal drugs. Neurological
      complications of Candida albicans infection are rare and prognosis is generally
      poor. This case report illustrates diagnostic and therapeutic difficulties
      encountered.

PMID- 11984493
TI  - [Visual field defect in a patient given sodium valporate then carbamazepine:
      possible effect of aminotransferase inhibition].
AB  - We report the case of a 25-years old woman with anti-epileptic drugs who presents
      a visual field defect similar to those described with vigabatrin even though she
      was successfully treated with valproic acid then carbamazepine without
      vigabatrin. The association with trichorrhexis nodosa, a hair disease sometimes
      associated with inherited perturbation of metabolism of urea cycle in which
      visual loss can occur, could suggest an aspecific inhibition of several
      aminotransferases which could explain different adverse effects of some anti
      epileptic drugs (visual abnormalities, alopecia) perhaps in genetic predisposed
      patients.

PMID- 11984494
TI  - [Acute confusion and cerebral infarcts].

PMID- 11984495
TI  - [Nerve biopsy].

PMID- 11984496
TI  - [ANOCEF MEETING December 8, 2001. Summary of the meeting].

PMID- 11984497
TI  - Intraosseous pleomorphic adenoma: case report and review of the literature.
AB  - Pleomorphic adenoma is the most common neoplasm of the salivary glands, affecting
      mainly the parotid gland. The preferential intraoral site of this tumor is the
      palate. A case of a 31-year-old woman with an intraosseous pleomorphic adenoma
      located in the maxilla (left paramedian region), showing an approximate evolution
      of one year is reported. The present intraosseous case represents a rare
      location, with the tumor probably originating from glandular epithelial remnants
      captured during embryogenesis. In a review of the literature of 142 cases of
      intragnathic localization (24% in the maxilla) are identified. A slight
      predominance of women was observed (56%), with 55% of the patients being affected
      during the 5th to 7th decade of life. The tumors were malignant in 94% of the
      cases, with special predominance of mucoepidermoid carcinoma (65%). Intraosseous
      pleomorphic adenomas are rare, with the present patient being the 6th case
      reported in the literature and the second found in the maxilla. Mean age of the 5
      previously reported cases was 58.8 years.

PMID- 11984498
TI  - Necessity for and control of dental treatment in HIV infected children. Inter
      professional relationship between dentist and paediatrician.
AB  - HIV infected children frequently suffer from buccal-dental lesions needing dental
      treatment. This treatment should improve their systemic affection, localised
      pathology, psychological and affective state and their general quality of life.
      Hardly any of these children are ever treated; sometimes because of lack of
      family motivation (the most frequent cause) and others because of the lack of a
      Paediatric Dental Unit in the hospitals they attend. For this reason we present
      here two cases of HIV infected children, with HIV infected mothers, who, thanks
      to the relationship between the Paediatric and Dental Units of the hospital, have
      had access to dental treatment for multiple caries and candidiasis. An
      anatopathological diagnosis of gingival inflammation, which was also infected by
      candida, was also carried out. The treatment included extraction of teeth,
      pulpotomy, pulpectomy and the fitting of prostheses. It should be made clear that
      a good inter-professional relationship is needed and it must also be taken into
      account the great difficulty that is encountered when trying to make this group
      of patients understand the need for, and benefits of, dental treatment.

PMID- 11984499
TI  - Primary herpetic gingivostomatitis in a 65-year-old patient.
AB  - We report a case of primary herpetic gingivostomatitis in a 65 years old patient.
      Age of onset for this disease is typically 1-5 years, though it may also arise in
      adolescents and young adults; it is rare in children of less than 6 months, as
      well as in adults more than 40 years old. Our case is thus, unusual in view of
      the patient's age. We discuss criteria for diagnosis in cases of this type.

PMID- 11984500
TI  - Prevalence of oral lesions in the 6-year-old pediatric population of Oviedo
      (Spain).
AB  - OBJECTIVE: The present study investigates the prevalence of oral diseases in
      children in the city of Oviedo (Spain). METHODS: A representative sample was
      selected from among the 6-year-old children in Oviedo (n= 786), involving a
      protocol developed for pediatric oral diseases. RESULTS: A total of 344 lesions
      were detected in 243 children. The most common disorder was saburral tongue
      (16,02%), followed by traumatisms (12.17%) and geographic tongue (4.48%). The
      prevalence of aphthous stomatitis was 2.24% and herpes labialis was 1,6%.
      Ankyloglossia was observed in 2.08% of cases, and a hypertrophic lip frenulum in
      1.28%. CONCLUSIONS: In this study shows the prevalence of the lesions of the oral
      mucosa in the Spanish population of 6 year-old. Of the results of the present
      study comes off that the objectives sanitary oral publics and deprived in this
      field they should go focused toward: 1) the eradication of illnesses of local
      cause (language saburral, traumatic ulcerations, etc.) for their high
      prevalencia; and, 2) the precocious diagnosis of anomalies of the development
      (anquiloglosias and labial frenum) for their relationship with dysfunctions of
      the phonation and future malocclusions.

PMID- 11984501
TI  - Idiopathic external root resorption associated to hypercalciuria.
AB  - Although external root resorption (ERR) is a physiological process in deciduous
      dentition, it is very infrequent in permanent dentition - where the phenomenon is
      related to the existence of inadequate occlusal forces, periodontal pathology and
      microtraumatisms, etc. However, in many cases root resorption cannot be
      attributed to any concrete cause; such cases are defined as idiopathic external
      root resorption (IERR). Epidemiological studies have found that the underlying
      cause can only be established in 5% of all ERR. The present study describes three
      cases of IERR with different degrees of involvement and associated to mild
      calciuria and a history of nephrolithiasis. Hypercalciuria with normal blood
      calcium levels is usually idiopathic and exhibits a familial trait, with a
      prevalence of 20-40 cases per 1,000 individuals in adults. A form of
      hypercalciuria associated to nephrolithiasis with a mutation of the CLCN5 gene
      has been identified, involving low molecular weight proteinuria - though this
      mutation has not been uniformly demonstrated in most cases of idiopathic
      hypercalciuria. The peculiarity of the cases described in the present study is
      attributable to the coexistence of IERR with normocalcemic hypercalciuria and
      nephrolithiasis - thus pointing to the need for in-depth evaluation of the
      possible association of these three clinical situations.

PMID- 11984502
TI  - Invasive maxillary aspergillosis: report of a case and review of the literature.
AB  - A case of invasive aspergillosis of the maxillary sinus in an immunocompromised
      patient is presented. Aspergillosis of the paranasal sinuses is uncommon,
      however, its incidence has shown a marked increase in number in the recent years.
      It has been classified into four types: allergic, noninvasive, invasive and
      fulminant. Immunocompromised patients are particularly at the risk of fulminant
      invasive aspergillosis. Early diagnosis is essential in order to avoid the high
      morbidity and mortality associated with the destructive disease and to instigate
      treatment before irreversible conditions arise.

PMID- 11984503
TI  - Quantitative and functional neutrophil deficiencies.
AB  - Neutrophil is a cell involved in the maintenance of homeostasis of the organism.
      It plays an important role in the elimination and control of certain pathogenic
      microorganisms. Deficiency in function and quantity of neutrophils, either due to
      congenital or secondary etiological extrinsic factors, lead to recurrent
      infectious processes of variable severity. The most frequent oral complications
      in these patients are ulcers, periodontal disease and candidiasis. Due to their
      high susceptibility to infections and the risk implied in undergoing surgical
      procedures, actions leading to a higher degree of prophylaxis must be carried out
      on these patients (oral hygiene habits, fluoridation, dietary advise, etc.). The
      use of granulocyte colony-stimulating factors (G-CSF) allows, in some cases, the
      fullfillment of some, until recently considered controversial dental procedures.
      Its administration demands an adequate selection of patients and a close
      collaboration between physician and dental practitioner. Despite G-CSF
      effectiveness, dental treatment in severe neutropenic patients must be carried
      out in a hospital and, in some cases, regardless of adequate care, the progress
      of periodontal disease cannot be avoided.

PMID- 11984504
TI  - Dental management of the patient with ischemic heart disease: an update.
AB  - Ischemic heart disease is the most common cause of death in developed countries.
      The classical protocols for providing dental care in these patients with chest
      angina or myocardial infarction were based on the classification of the American
      Society of Anesthesiologists (ASA), postponing therapy for a minimum of 6 months
      after infarction in order to ensure safer dental treatment. However, advances in
      diagnostic techniques and medical and surgical treatments in patients with heart
      disease have led to the development of more precise risk assessment protocols,
      thus allowing earlier post-infarction dental treatments and oral surgery, with
      acceptable safety margins.

PMID- 11984505
TI  - Dental gemination: report of case.
AB  - Dental anomalies can be classified in different groups: anomalies of volume,
      anomalies of number, anomalies of form, anomalies of position and anomalies by
      union. Of the latter, we distinguish between fusion, alveolus-dental gemination,
      concrescence, coalescence and anchylosis. Gemination is more frequent in the
      anterior teeth, although it can also affect the bicuspids and molars, being an
      anomaly of infrequent union (prevalence 0.5%). We present the case of a young
      male patient age 19, without medical antecedents of interest, that goes to
      consultation for repeated inflammatory accidents at level of the inferior left
      retromolar area. These episodes are caused by a semi-impacted inferior third
      molar that is fused to a supernumerary fourth molar, sharing its roots, crown,
      pulp chambers and canals. After the appropriate radiologic study and suitable
      planning, the semi-impacted third molar was extracted under local anaesthesia and
      without any other complications during or after the operation.

PMID- 11984506
TI  - Activated virus-specific T cells are early indicators of anti-CMV immune
      reactions in liver transplant patients.
AB  - BACKGROUND & AIMS: Cytomegalovirus (CMV) infection represents the most common
      infectious complication after liver transplantation. Because CMV-associated
      complications in liver transplantation patients are often liver-restricted and
      clinically unrecognized, diagnosis of early infection or reactivation is still
      very difficult. Because cytotoxic T cells (CTLs) are crucial for the immune
      control of CMV, analysis of virus-specific CTLs could contribute to diagnosis and
      management of CMV infection. METHODS: Major histocompatibility complex class I
      tetramers and intracellular cytokine staining were used to determine frequencies
      and phenotypes of peripheral blood CMV/pp65-specific CD8(+) T cells in HLA-A2, 
      B7, and -B35 positive liver transplantation patients and in healthy individuals.
      RESULTS: After liver transplantation (6-33 months after liver transplantation),
      frequencies of CMV-specific T cells were significantly elevated compared with
      healthy individuals. In contrast to immunoglobulin (Ig) M-negative patients and
      healthy blood donors, patients with increasing CMV IgM titers or IgG
      seroconversion had high percentages of activated (CD38(high)) CMV-specific T
      cells. In recently transplanted patients, activation of CMV-specific T cells was
      associated with increased transaminases and histopathological abnormalities in
      the absence of positive CMV-polymerase chain reaction results from peripheral
      blood. CONCLUSIONS: These data indicate that T-cell analysis based on MHC
      tetramer staining may be a valuable parameter in the early diagnosis of CMV
      induced, liver-restricted complications after liver transplantation.

PMID- 11984507
TI  - Eosinophilic esophagitis in children: immunopathological analysis and response to
      fluticasone propionate.
AB  - BACKGROUND & AIMS: Eosinophilic esophagitis (EE) shares symptoms with
      gastroesophageal reflux disease but has distinctive pathologic features and
      unknown immunopathology. Treatments with antigen restriction or systemic
      immunosuppression pose problems with compliance and side effects. Topically
      applied steroids offer an attractive alternative treatment. The aims of this
      study were to determine the immunopathologic features of EE and the effectiveness
      of antigen-specific diet restriction (DR) and topical immunosuppression. METHODS:
      A prospective trial was conducted examining the impact of DR and swallowed
      fluticasone propionate (FP) on pediatric patients with EE. Clinicopathologic
      features, including immunohistochemical analysis of the esophageal mucosa, were
      measured before and after treatment. RESULTS: Immunohistochemical analysis of 11
      prospectively identified children showed a significantly greater number of
      mucosal CD3 and CD8 lymphocytes, as well as CD1a antigen-presenting cells
      compared with normal controls. DR did not induce clinical improvement in any
      patients, whereas all children who completed treatment with FP had resolution of
      symptoms. Posttreatment analysis of proximal and distal esophageal mucosa showed
      a significant reduction in the number of eosinophils, as well as CD3(+) and
      CD8(+) lymphocytes compared with pretreatment sections. CONCLUSIONS: EE is
      characterized by immunologically active esophageal mucosa. FP, not DR,
      effectively relieves symptoms. FP significantly reduces mucosal inflammation
      associated with EE.

PMID- 11984508
TI  - On-site screening sigmoidoscopy promotes long-term utilization but fails as a
      venue for training primary care endoscopists.
AB  - BACKGROUND & AIMS: "Academic detailing" is an effective strategy for promoting
      the use of screening sigmoidoscopy by primary care physicians. The primary
      objectives of this study were to determine whether the sustained presence of an
      "outside" university-based gastroenterologist performing on-site screening
      sigmoidoscopy promoted long-term utilization and whether the provision for on
      site sigmoidoscopy was an effective venue for training primary care endoscopists.
      METHODS: Nine urban community health centers, including 4 intervention and 5
      control sites, participated in a nonrandomized controlled trial conducted over 3
      years. RESULTS: By the end of year 3, overall self-reported use of screening
      sigmoidoscopy increased by 61% for the intervention group vs. only 25% for the
      comparison group (P = 0.001). Ninety-seven percent of those reporting compliance
      referred 1 or more asymptomatic average-risk patients for screening examinations.
      Only 2 of 83 (2.4%) eligible providers completed on-site training and continued
      performing screening examinations independently. The major barriers to
      participation included lack of interest, lack of time to learn or perform
      sigmoidoscopy, concerns about technical competence, and lack of need because of
      on-site availability. CONCLUSIONS: Maintenance of on-site screening sigmoidoscopy
      services performed by an outside gastroenterologist promotes long-term
      utilization but fails as venue for training primary care endoscopists.
      Alternative strategies for expanding capacity are needed.

PMID- 11984509
TI  - The true impact of fatigue in primary biliary cirrhosis: a population study.
AB  - BACKGROUND & AIMS: Patient surveys suggest that fatigue is a common problem in
      primary biliary cirrhosis (PBC). The actual extent of the problems caused by
      fatigue in PBC has yet to be determined as previous studies addressing this
      question have tended to use selected patient subgroups and subjective or non
      quantitative fatigue assessment tools. Here, we have attempted to more accurately
      assess the extent of fatigue in PBC, and the specificity of the symptom for this
      disease, by the application of an objective measure of fatigue impact (the
      fatigue impact score [FIS]) to a geographically based patient cohort, age- and
      sex-matched normal controls, and chronic liver disease controls. METHODS: Postal
      completion of the FIS and linked symptom assessment tools. RESULTS: Median FIS
      was significantly higher in patients (n = 136) than community controls (40 [0
      138] vs. 28 [0-156]; P < 0.0001) and chronic liver disease controls (n = 38)
      (20.5 [0-145]; P < 0.05). Fatigue scores in the 11 patients who had undergone
      liver transplantation (median 3.5 years previously) were the same as those in non
      transplanted patients with advanced disease. CONCLUSIONS: Fatigue is a
      significant and specific problem in PBC. It is not, however, universal and
      affects fewer patients than has previously been thought to be the case based on
      data from selected patient cohorts. This definition of the "normal range" for
      fatigue in PBC will assist in future studies of etiology and therapy.

PMID- 11984510
TI  - The value of serologic markers in indeterminate colitis: a prospective follow-up
      study.
AB  - BACKGROUND & AIMS: In the absence of pathognomonic markers for Crohn's disease
      (CD) and ulcerative colitis (UC), the diagnosis of inflammatory bowel disease
      depends on a compendium of clinical, radiographic, endoscopic, and histologic
      criteria that bears imperfect specificity to the individual disorders. In 10% of
      cases of colitis, no differentiation can be made between CD and UC; these
      patients are diagnosed with indeterminate colitis (IC). We evaluated the value of
      anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil
      cytoplasmic antibodies (pANCA) to increase diagnostic accuracy in categorizing
      IC. METHODS: Since 1996, 97 patients with IC from 3 centers (Leuven, Lille, and
      Vienna) were enrolled, analyzed for pANCA and ASCA, and followed up
      prospectively. RESULTS: A definitive diagnosis has been reached for 31 of 97
      patients (32%). In these patients, ASCA+/pANCA- correlated with CD in 8 of 10
      patients, whereas ASCA-/pANCA+ correlated with UC in 7 of 11 patients. The
      remaining 4 cases became CD, clinically behaving as UC-like CD. Almost half of
      the patients (47 of 97 [48.5%]) were negative for ASCA and pANCA, and 40 remain
      diagnosed with IC to date. Only 7 seronegative cases (14.9%) became CD or UC
      compared with 48% (24 of 50) of seropositive patients (P < 0.001). CONCLUSIONS:
      Results so far show that ASCA+/pANCA- predicts CD in 80% of patients with IC and
      ASCA-/pANCA+ predicts UC in 63.6%. Interestingly, 48.5% of patients do not show
      antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC
      during their further clinical course, perhaps reflecting a distinct
      clinicoserological entity.

PMID- 11984511
TI  - Dietary nitrate generates potentially mutagenic concentrations of nitric oxide at
      the gastroesophageal junction.
AB  - BACKGROUND & AIMS: Twenty-five percent of absorbed dietary nitrate is re-secreted
      in saliva, and 30% of this is reduced to nitrite by buccal bacteria. When saliva
      is swallowed, the acidic gastric juice reduces the nitrite to nitric oxide. The
      aim of this study was to examine the anatomic distribution of nitric oxide
      generation within the lumen of the upper gastrointestinal tract under basal
      conditions and after ingesting nitrate equivalent to that in salad portion.
      METHODS: Using custom-made sensors, the dissolved luminal nitric oxide
      concentration and pH were measured at 1-cm increments for 2 minutes throughout
      the length of the stomach and distal esophagus in 15 Helicobacter pylori-negative
      healthy volunteers with and without ingestion of 2 mmol potassium nitrate. Serum
      nitrate and saliva nitrite concentrations were also monitored. RESULTS: The
      nitrate ingestion increased mean (range) serum nitrate from 30 micromol/L (18-49)
      to 95 micromol/L (32-152), mean salivary nitrite from 36 micromol/L (19-153) to
      252 micromol/L (32-600), and mean peak luminal nitric oxide concentration from
      4.7 micromol/L (1.4-7.8) to 23.2 micromol/L (2.1-50) (P < 0.05 for each). After
      nitrate, the peak nitric oxide concentration occurred in 11 of the 15 (73%)
      subjects within 1 cm distal to the gastroesophageal pH step-up point. The mean
      nitric oxide concentration over the 1-cm segment immediately distal to the
      gastroesophageal pH step-up after nitrate was 7.5 micromol/L (range, 0.5-30.7)
      and was significantly higher than at all other sites. Nitric oxide concentrations
      greater than 50 micromol/L were observed at the precise location where neutral
      esophageal pH fell to acidic gastric pH. CONCLUSIONS: Luminal generation of
      nitric oxide from dietary nitrate via salivary nitrite is maximal at the
      gastroesophageal junction and cardia. The high concentrations of nitric oxide
      generated may contribute to the high incidence of mutagenesis and neoplasia at
      this site.

PMID- 11984512
TI  - Abnormal esophageal motility in children with congenital central hypoventilation
      syndrome.
AB  - BACKGROUND & AIMS: Congenital central hypoventilation syndrome, an unexplained
      disorder of the central control of breathing that may reflect widespread
      dysfunction of brainstem structures, is regarded as a form of neuro cristopathy.
      Because swallowing-induced peristalsis is centrally controlled and depends on
      neural crest-derived esophageal innervation, we looked for esophageal dysmotility
      in patients with congenital central hypoventilation syndrome. METHODS: Seven
      patients without dysphagia or any other upper gastrointestinal tract symptoms
      were studied prospectively (5 girls and 2 boys; median age, 14 years; range, 11
      18 years). They were compared with 7 age- and sex-matched controls. Esophageal
      manometry was performed using a low-compliance infusion system and the station
      pull-through technique. At least 10 wet swallows were analyzed in each subject.
      RESULTS: Pressure wave propagation was abnormal in all 7 patients (median
      percentage of swallows propagated, 18%, and range, 0-66; controls, 90% and 80
      100; P < 0.001). Lower esophageal sphincter relaxation was abnormal in 5 patients
      (patients, 73% and 53-100; controls, 95% and 90-100; P = 0.01). In 2 patients,
      lower esophageal sphincter pressure was above the 95th percentile of control
      values. CONCLUSIONS: These abnormalities are strong evidence of lower esophageal
      dysfunction in congenital central hypoventilation syndrome. We speculate that the
      underlying mechanism may be dysfunction of the central structures that control
      swallowing.

PMID- 11984513
TI  - HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the
      Japanese population.
AB  - BACKGROUND & AIMS: Autoimmune pancreatitis is a distinctive disease entity
      characterized by high serum immunoglobulin G4 concentrations. Because of the
      close association between some autoimmune diseases and particular alleles of
      major histocompatibility complex genes, we investigated the association between
      HLA alleles and autoimmune pancreatitis. METHODS: HLA-A, -B, -C, -DR, and -DQ
      gene typing and HLA-DRB1, -DQB1, and -DPB1 allele typing were performed by the
      polymerase chain reaction sequence-specific primers method and the restriction
      fragment length polymorphism method, respectively, in 40 patients with autoimmune
      pancreatitis, 43 patients with chronic calcifying pancreatitis, and 201 healthy
      subjects. RESULTS: In patients with autoimmune pancreatitis compared with healthy
      subjects, we found a significant increase in DR4 (73% vs. 44%, corrected P =
      0.01) and DRB1*0405 (58% vs. 21%, corrected P = 0.000026) and DQ4 (58% vs. 26%,
      corrected P = 0.001) and DQB1*0401 (58% vs. 21%, corrected P = 0.000017). The
      DRB1*0405-DQB1*0401 haplotype in autoimmune pancreatitis showed no significant
      association with any HLA class I antigens, in contrast to the B54-DRB1*0405
      DQB1*0401 haplotype reported in autoimmune hepatitis. The frequencies of
      DRB1*0405 and DQB1*0401 were significantly high in patients with autoimmune
      pancreatitis compared with chronic calcifying pancreatitis. CONCLUSIONS: It is
      probable that DRB1*0405-DQB1*0401 haplotype is associated with autoimmune
      pancreatitis in the Japanese population.

PMID- 11984514
TI  - Dyspepsia management in primary care: a decision analysis of competing
      strategies.

PMID- 11984515
TI  - T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond
      to H. pylori eradication.
AB  - BACKGROUND & AIMS: Eradication of Helicobacter pylori leads to cure of gastric
      mucosa-associated lymphoid tissue (MALT) lymphoma in 75% of localized cases.
      However, prolonged follow-up is necessary to determine whether a lymphoma
      responds to therapy. In a small series of cases, we showed that t(11;18)(q21;q21)
      positive MALT lymphomas failed to respond to H. pylori eradication. The present
      study aimed to verify this finding in a large cohort and confirm whether the
      translocation predicts the response of stage I(E) tumors, for which clinical
      staging has little prognostic value. METHODS: A total of 111 patients with H.
      pylori-positive gastric MALT lymphoma treated with antibiotics were studied.
      Clinical staging was undertaken before therapy. The response of lymphoma to H.
      pylori eradication was determined by histologic examination of gastric biopsy
      specimens. Diagnostic biopsy specimens were analyzed for t(11;18)(q21;q21) by
      reverse-transcription polymerase chain reaction of the API2-MALT1 transcript.
      RESULTS: Forty-seven of the 48 patients who showed complete regression had
      lymphoma at stage I(E), whereas 43 of the 63 nonresponsive cases were at stage
      I(E) and the remaining cases at stage II(E) or above. t(11;18)(q21;q21) was
      detected in 2 of 48 complete-regression cases, and these positive cases showed
      relapse of lymphoma in the absence of H. pylori reinfection. In contrast, the
      translocation was present in 42 of the 63 nonresponsive cases, including 26 of 43
      (60%) at stage I(E). CONCLUSIONS: t(11;18)(q21;q21)-positive gastric MALT
      lymphomas, including those at stage I(E), do not respond to H. pylori
      eradication. Detection of the translocation should help the clinical management
      of patients with gastric MALT lymphoma.

PMID- 11984516
TI  - Clinical and pathologic findings in hemochromatosis type 3 due to a novel
      mutation in transferrin receptor 2 gene.
AB  - BACKGROUND & AIMS: Although most patients with hereditary hemochromatosis are
      homozygous for a single mutation of the HFE gene on chromosome 6p, accumulating
      evidence indicates that the disease is genetically heterogeneous. Type 3
      hemochromatosis, recently described in 4 families, is linked to mutations of the
      gene encoding transferrin receptor 2 on chromosome 7q22. Here we report data from
      a family carrying a new mutation of the transferrin receptor 2 gene. METHODS:
      Detailed clinical and histopathologic documentation was available for most family
      members. The entire coding sequence and exon/intron boundaries of the transferrin
      receptor 2 gene were analyzed by direct sequencing. RESULTS: A 12-nucleotide
      deletion in exon 16, causing the loss of 4 amino acids (AVAQ 594-597 del), was
      detected at the homozygous state in the 3 patients with histologically proven
      iron overload. The deletion segregated with the disease within the family and was
      not found in 100 healthy controls. Some clinical and pathologic characteristics,
      such as low penetrance in the premenopausal woman, and early iron deposition in
      periportal hepatocytes resembled those of classic, HFE-related hemochromatosis.
      CONCLUSIONS: Our data support the role of the transferrin receptor 2 gene in
      hemochromatosis type 3 as well as its critical involvement in the maintenance of
      iron homeostasis in humans.

PMID- 11984517
TI  - Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in
      patients with chronic hepatitis C.
AB  - BACKGROUND & AIMS: Liver fibrosis is an important prognostic factor in patients
      with hepatitis C. The effect of pegylated (PEG) interferon alone or its
      combination with ribavirin on fibrosis has not been established. METHODS: We
      pooled individual data from 3010 naive patients with pretreatment and
      posttreatment biopsies from 4 randomized trials. Ten different regimens combining
      standard interferon, PEG interferon, and ribavirin were compared. The impact of
      each regimen was estimated by the percentage of patients with at least 1 grade
      improvement in the necrosis and inflammation (METAVIR score), the percentage of
      patients with at least 1 stage worsening in fibrosis METAVIR score, and by the
      fibrosis progression rate per year. RESULTS: Necrosis and inflammation
      improvement ranged from 39% (interferon 24 weeks) to 73% (optimized PEG 1.5 and
      ribavirin; P < 0.001). Fibrosis worsening ranges from 23% (interferon 24 weeks)
      to 8% (optimized PEG 1.5 and ribavirin; P < 0.001). All regimens significantly
      reduced the fibrosis progression rates in comparison to rates before treatment.
      The reversal of cirrhosis was observed in 75 patients (49%) of 153 patients with
      baseline cirrhosis. Six factors were independently associated with the absence of
      significant fibrosis after treatment: baseline fibrosis stage (odds ratio [OR] =
      0.12; P < 0.0001), sustained viral response (OR = 0.36; P < 0.0001), age < 40
      years (OR = 0.51; P < 0.001), body mass index < 27 kg/m(2) (OR = 0.65; P <
      0.001), no or minimal baseline activity (OR = 0.70; P = 0.02), and viral load <
      3.5 millions copies per milliliter (OR = 0.79; P = 0.03). CONCLUSIONS: PEG
      interferon and ribavirin combination significantly reduces the rate of fibrosis
      progression in patients with hepatitis C.

PMID- 11984518
TI  - Rehabilitation of swallowing by exercise in tube-fed patients with pharyngeal
      dysphagia secondary to abnormal UES opening.
AB  - BACKGROUND & AIMS: We evaluated the effect of a novel rehabilitative exercise on
      restoration of deglutition in a group of patients with deglutitive failure caused
      by abnormal upper esophageal sphincter (UES) opening manifested by postswallow
      residue and aspiration necessitating percutaneous tube feeding. METHODS: We
      studied a total of 27 patients by videofluoroscopy and functional assessment of
      swallowing scores before and after 6 weeks of a head-raising exercise program.
      Seven of 27 patients, assigned randomly, participated in a sham exercise before
      entering the tested exercise program. Eleven of 27 were randomized to the real
      exercise program. RESULTS: Although there was no change in swallow function and
      biomechanics after the sham exercise, following 6 weeks of real exercise, all 11
      patients exhibited a significant improvement in their UES opening, anterior
      laryngeal excursion (P < 0.01), as well as resolution of postdeglutitive
      aspiration and were able to resume oral feeding. Similar results were found when
      the 7 patients in the sham group were crossed over to the real exercise group.
      Comparison of before and after exercise values for anteroposterior UES opening (P
      < 0.01) and laryngeal anterior excursion (P < 0.05), as well as functional
      outcome assessment of swallowing (P < 0.05) in the entire group of 27 patients
      also showed significant improvement. Etiology and duration of dysphagia did not
      affect the outcome. CONCLUSIONS: The proposed suprahyoid muscle strengthening
      exercise program is effective in restoring oral feeding in some patients with
      deglutitive failure because of abnormal UES opening.

PMID- 11984519
TI  - H/dipeptide absorption across the human intestinal epithelium is controlled
      indirectly via a functional Na/H exchanger.
AB  - BACKGROUND & AIMS: For optimal nutrient absorption to occur, the enterocyte must
      express a range of specialist ion-driven carrier proteins that function
      cooperatively in a linked and mutually dependent fashion. Thus, absorption via
      the human intestinal H(+)-coupled di/tripeptide transporter (hPepT1) is dependent
      on maintenance of the trans-apical driving force (the H(+)-electrochemical
      gradient) established, in part, by brush-border Na(+)/H(+) exchanger (NHE3)
      activity. This study aimed to examine whether physiologic regulation of NHE3
      activity can limit hPepT1 capacity and, therefore, protein absorption after a
      meal. METHODS: hPepT1 and NHE3 activities were determined in intact human
      intestinal epithelial Caco-2 cell monolayers by measurements of
      [(14)C]glycylsarcosine transport and uptake, (22)Na(+)-influx, H(+)-influx, and
      H(+)-efflux. Expression of NHE regulatory factors was determined by reverse
      transcriptase polymerase chain reaction. RESULTS: Optimal dipeptide transport was
      observed in the presence of a transapical pH gradient and extracellular Na(+). At
      apical pH 6.5, and only in Na(+)-containing media, protein kinase A activation
      (by forskolin or vasoactive intestinal peptide) or selective NHE3 inhibition (by
      S1611) reduced transepithelial dipeptide transport and cellular accumulation by a
      reduction in the capacity (without effect on affinity) of dipeptide uptake.
      CONCLUSIONS: Protein kinase A-mediated modulation of intestinal dipeptide
      absorption is indirect via effects on the apical Na(+)/H(+) exchanger.

PMID- 11984520
TI  - Critical role of caspases in the regulation of apoptosis and proliferation of
      mucosal T cells.
AB  - BACKGROUND & AIMS: Caspases are critical mediators of apoptosis and proliferation
      of peripheral blood T cells (PBT), but their role in lamina propria T cells
      (LPT), a cell population highly susceptible to apoptosis, has not been explored.
      METHODS: RA(+), RO(+) PBT, and LPT were activated with CD3, CD2, and CD28
      antibodies, and caspase activity, apoptosis, and proliferation were measured by a
      fluorometric assay, DNA content, and thymidine incorporation, respectively.
      Levels of FLIP, an endogenous inhibitor of caspase 8, were measured by
      immunoblotting. RESULTS: In RA(+) and RO(+) PBT, activation leads to significant
      increase of caspase activity but not cell death, whereas in LPT a lower elevation
      of caspase activity was followed by a marked degree of apoptosis. Based on the
      results of its inhibition, caspase 8 seemed to be essential for LPT apoptosis
      but, in contrast to RA(+) PBT, had no effect on proliferation. In addition,
      compatible with their differential susceptibility to apoptosis, levels of FLIP
      were lower in LPT than PBT. CONCLUSIONS: The high susceptibility of LPT to
      apoptosis is associated with a distinct regulation of caspase 8 activity, which
      seems to reflect their mucosal origin rather than simply their memory status.
      This unique behavior may allow proper control of mucosal T-cell proliferation
      while still permitting elimination by apoptosis in the face of excessive
      antigenic pressure.

PMID- 11984521
TI  - Monoassociation of SCID mice with Helicobacter muridarum, but not four other
      enterics, provokes IBD upon receipt of T cells.
AB  - BACKGROUND & AIMS: Recently, a number of animal models for different aspects of
      inflammatory bowel disease (IBD) have been developed. The aim of this study was
      to use one of these to determine whether particular, ostensibly innocuous,
      intestinal bacteria could provoke or exacerbate IBD. METHODS: Conventionally
      reared C.B17 SCID mice were compared with germ-free and gnotobiotic mice,
      monoassociated with 1 of 5 intestinal bacteria, after transfer of CD45RB(high)
      CD4(+) T cells from conventionally reared congenic BALB/c mice. Recipient mice
      were monitored over 7-12 weeks for clinical signs of IBD, and tissues were
      analyzed by histology/flow cytometry for abnormal inflammation and CD4(+) T cell
      outgrowth. RESULTS: Neither germ-free mice nor mice monoassociated with segmented
      filamentous bacteria, Ochrobactrum anthropi, a nonpathogenic mutant of Listeria
      monocytogenes, or Morganella morganii developed any signs of IBD. In contrast,
      mice monoassociated with Helicobacter muridarum displayed an accelerated
      development of IBD in 5-6 weeks compared with 8-12 weeks observed in
      conventionally reared mice. The outgrowth of CD4(+) T cells in spleen and large
      intestine of H. muridarum monoassociated mice, as well as in conventionally
      reared mice was significantly higher than that in the other monoassociated mice.
      CONCLUSIONS: Among the intestinal bacteria tested, H. muridarum can serve as a
      provocateur of IBD in this model.

PMID- 11984522
TI  - NO sensitizes rat hepatocytes to proliferation by modifying S-adenosylmethionine
      levels.
AB  - BACKGROUND & AIMS: Liver regeneration is a fundamental response of this organ to
      injury. Hepatocyte proliferation is triggered by growth factors, such as
      hepatocyte growth factor. However, hepatocytes need to be primed to react to
      mitogenic signals. It is known that nitrous oxide (NO), generated after partial
      hepatectomy, plays an important role in hepatocyte growth. Nevertheless, the
      molecular mechanisms behind this priming event are not completely known. S
      adenosylmethionine (AdoMet) synthesis by methionine adenosyltransferase is the
      first step in methionine metabolism, and NO regulates hepatocyte S
      adenosylmethionine levels through specific inhibition of this enzyme. We have
      studied the modulation of hepatocyte growth factor-induced proliferation by NO
      through the regulation of S-adenosylmethionine levels. METHODS: Studies were
      conducted in cultured rat hepatocytes isolated by collagenase perfusion, which
      triggers NO synthesis. RESULTS: The mitogenic response to hepatocyte growth
      factor was blunted when inducible NO synthase was inhibited; this process was
      overcome by the addition of an NO donor. This effect was dependent on methionine
      concentration in culture medium and intracellular S-adenosylmethionine levels.
      Accordingly, we found that S-adenosylmethionine inhibits hepatocyte growth factor
      induced cyclin D1 and D2 expression, activator protein 1 induction, and
      hepatocyte proliferation. CONCLUSIONS: Together our findings indicate that NO may
      switch hepatocytes into a hepatocyte growth factor-responsive state through the
      down-regulation of S-adenosylmethionine levels.

PMID- 11984523
TI  - The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in
      the murine intestinal mucosa.
AB  - BACKGROUND & AIMS: Apoptosis is especially relevant in the gastrointestinal tract
      because the mammalian intestinal mucosa undergoes continual epithelial
      regeneration. Most recently, we confirmed the proapoptotic role of endogenous
      transforming growth factor (TGF)-beta in the developing chick retina as well as
      in chick ciliary, dorsal root, and spinal motor neurons. In the present study, we
      determined to establish the role of TGF-beta2 and TGF-beta3 in mediating
      apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of
      Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice. METHODS: Intestinal
      localization of TGF-beta2 and TGF-beta3 isoforms and antiapoptotic molecules Bcl
      xL and Bcl-2 was examined immunocytochemically and by Western blot analysis.
      Apoptosis was detected by enzyme-linked immunosorbent assay and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling, and proliferation was detected by proliferating cell nuclear antigen
      stains. RESULTS: TGF-beta2 was detected in endocrine cells, whereas TGF-beta3 was
      predominantly found in goblet cells. Programmed cell death was significantly
      reduced in the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous
      mice. This decrease in apoptosis was accompanied by an increase in villus length;
      proliferation, however, seemed to remain unchanged. The level of Bcl-xL and Bcl-2
      was significantly up-regulated in Tgfbeta2(+/-) and Tgfbeta3(+/-) mice.
      CONCLUSIONS: Our data show that TGF-beta2 and TGF-beta3 play an important role in
      mediating apoptosis in the intestinal mucosa and regulating apoptosis-associated
      proteins Bcl-xL and Bcl-2 in vivo.

PMID- 11984524
TI  - CpG island methylation in sporadic colorectal cancers and its relationship to
      microsatellite instability.
AB  - BACKGROUND & AIMS: Methylation of CpG islands is increasingly recognized as an
      important event in colorectal carcinogenesis. We evaluated the extent of CpG
      island methylation in 426 sporadic colorectal cancers to define its relationship
      to microsatellite instability and to describe its clinicopathologic and genetic
      features. METHODS: Fresh cancer tissue was obtained from 417 consecutive
      individuals undergoing curative surgery for sporadic colorectal cancer.
      Methylation of p16 and hMLH1 promoters was determined by methylation-specific
      polymerase chain reaction (PCR), whereas methylation at MINT 1, 2, 12, and 31
      loci was assessed by bisulfite PCR. Microsatellite instability and K-ras and p53
      status were determined using microsatellite PCR, restriction enzyme-mediated PCR,
      and immunohistochemistry, respectively. RESULTS: Individual loci were commonly
      methylated, but locus-specific phenotypic changes were not seen. CpG island
      methylation was associated with right-sided location, female sex, and older age,
      as well as high tumor grade, mucinous type, wild-type P53, microsatellite
      instability, and K-ras mutations. More than half of tumors showing CpG island
      methylation were microsatellite stable. Compared with microsatellite unstable
      cancers, they were more commonly left-sided, had fewer intraepithelial
      lymphocytes, presented later, and had a worse outcome. CONCLUSIONS: Colorectal
      cancers with CpG island methylation have distinct clinicopathologic features and
      in some cases lead to sporadic microsatellite unstable cancers.

PMID- 11984525
TI  - Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene
      (NAG-1) in human and mouse tissue.
AB  - BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce NSAID
      activated gene 1 (NAG-1), which has proapoptotic and antitumorigenic activities.
      However, NAG-1 expression and its relationship with apoptosis in human and mouse
      intestinal tract have not been determined. METHODS: NAG-1 expression in human and
      mouse tissue was determined by immunohistochemistry, and apoptosis was estimated
      by in situ apoptosis detection. Apoptosis in NAG-1 overexpressing HCT-116 cells
      was examined with flow cytometry after cell sorting by green fluorescence
      protein. NAG-1 regulation in mouse cells was examined by Northern blot analysis,
      comparing sulindac-treated and nontreated mice. RESULTS: Apoptosis was higher in
      NAG-1 overexpressing cells compared with controls. Human NAG-1 protein was
      localized to the colonic surface epithelium where cells undergo apoptosis, and
      higher expression was observed in the normal surface epithelium than in most of
      the tumors. This localization and lower expression in tumors was similar to that
      in the Min mouse, in which NSAIDs were also shown to regulate the expression of
      NAG-1 in mouse cells. Sulindac treatment of mice increased the NAG-1 expression
      in the colon and liver. CONCLUSIONS: Based on these results, we propose that NAG
      1 acts as a mediator of apoptosis in intestinal cells and may contribute to
      cancer chemoprevention by NSAIDs.

PMID- 11984526
TI  - Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling
      of extracellular matrix in the rat.
AB  - BACKGROUND & AIMS: In this study, we investigated the role of leptin and its
      receptors (Ob-R) in profibrogenic responses in the liver using Zucker (fa/fa)
      rats, a natural occurring Ob-R-deficient animal. METHODS: Male Zucker (fa/fa)
      rats and their lean (+/?) littermates were given intraperitoneal injections of
      thioacetamide (TAA) (200 mg/kg body wt, 3 times/wk) for 4-8 weeks, and
      progression of hepatic fibrosis was evaluated. In vitro transactivation of
      hepatic stellate cells (HSCs) isolated from Zucker rats was evaluated by Western
      blotting and immunocytochemistry for alpha-smooth muscle actin and type I
      collagen. Further, a long-form Ob-R (Ob-Rb) in sinusoidal endothelial cells
      (SECs) and Kupffer cells was identified by reverse-transcription polymerase chain
      reaction. Moreover, transforming growth factor (TGF)-beta1 messenger RNA in LSE
      cells, a human SEC-derived cell line, was measured by Northern blotting. RESULTS:
      Although the normal liver does not produce leptin, activated HSCs produced leptin
      in vivo during fibrogenesis caused by TAA. In Zucker rats, TAA-induced hepatic
      fibrosis was prevented almost completely, whereas induction of TGF-beta1 and
      activation of HSCs were abolished. It is less likely, however, that leptin plays
      an essential role in the activation of HSCs as a strong autocrine regulator,
      because HSCs isolated from Zucker rats undergo normal transactivation process in
      vitro. In contrast, SECs and Kupffer cells contain Ob-Rb, through which leptin up
      regulates the expression of matrix remodeling genes including TGF-beta1.
      CONCLUSIONS: Collectively, these findings indicated that leptin and its
      functional receptors (Ob-Rb) play a pivotal role in profibrogenic responses in
      the liver.

PMID- 11984527
TI  - Taurolithocholic acid-3 sulfate induces CD95 trafficking and apoptosis in a c-Jun
      N-terminal kinase-dependent manner.
AB  - BACKGROUND & AIMS: Prevention of bile acid-induced apoptosis is of therapeutic
      interest and requires the understanding of underlying mechanisms. METHODS: The
      effect of tauroursodeoxycholate (TUDC) on taurolithocholic acid-3 sulfate (TLCS)
      induced apoptosis was studied in cultured rat hepatocytes. RESULTS: TLCS induced
      activation of caspases 8, 9, and 3 and hepatocyte apoptosis. These effects were
      abolished by TUDC in a PI 3-kinase-/protein kinase B (PKB)-, p38(MAPK)-, and
      extracellular signal-regulated kinase-2 (Erk-2)-independent manner. These protein
      kinases were activated by both TLCS and TUDC, however, with different kinetics.
      TLCS, but not TUDC, led to a sustained activation of c-Jun N-terminal kinase
      (JNK) and CD95 trafficking to the plasma membrane; both TLCS effects were
      prevented by TUDC. Inhibition of JNK1 or protein kinase C prevented TLCS-induced
      CD95 membrane trafficking and blunted the apoptotic response. The apoptotic
      potency of other bile acids paralleled their ability to induce sustained JNK
      activation. CONCLUSIONS: Protection by TUDC against TLCS-induced apoptosis starts
      upstream of caspase 8 activation and is independent of a PI 3-kinase-dependent
      survival pathway. JNK activation may be important for bile acid-induced apoptosis
      by triggering ligand-independent CD95 surface trafficking and activation of
      apoptosis.

PMID- 11984528
TI  - Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis.
AB  - BACKGROUND & AIMS: Impaired mucosal barrier, cytokine imbalance, and dysregulated
      CD4(+) T cells play important roles in the pathogenesis of experimental colitis
      and human inflammatory bowel disease. Immunostimulatory DNA sequences (ISS-DNA)
      and their synthetic oligonucleotide analogs (ISS-ODNs) are derived from bacterial
      DNA, are potent activators of innate immunity at systemic and mucosal sites, and
      can rescue cells from death inflicted by different agents. We hypothesized that
      these combined effects of ISS-DNA could inhibit the damage to the colonic mucosa
      in chemically induced colitis and thereby limit subsequent intestinal
      inflammation. METHODS: The protective and the anti-inflammatory effect of ISS-ODN
      administration were assessed in dextran sodium sulfate-induced colitis and in 2
      models of hapten-induced colitis in Balb/c mice. Similarly, these effects of ISS
      ODN were assessed in spontaneous colitis occurring in IL-10 knockout mice.
      RESULTS: In all models of experimental and spontaneous colitis examined, ISS-ODN
      administration ameliorated clinical, biochemical, and histologic scores of
      colonic inflammation. ISS-ODN administration inhibited the induction of colonic
      proinflammatory cytokines and chemokines and suppressed the induction of colonic
      matrix metalloproteinases in both dextran sodium sulfate- and hapten-induced
      colitis. CONCLUSIONS: As the colon is continuously exposed to bacterial DNA,
      these findings suggest a physiologic, anti-inflammatory role for
      immunostimulatory DNA in the GI tract. Immunostimulatory DNA deserves further
      evaluation for the treatment of human inflammatory bowel disease.

PMID- 11984529
TI  - Constitutive expression and function of cyclooxygenase-2 in murine gastric
      muscles.
AB  - BACKGROUND & AIMS: Cyclooxygenase enzymes (COX) generate intermediates in the
      prostaglandin (PG) cascade. COX-1 is constitutively expressed in many cells, and
      COX-2 is typically thought to be an inducible isoform. METHODS: We evaluated
      constitutive expression and function of COX-2 in murine gastric muscles. RESULTS:
      Immunohistochemistry showed COX-2-like immunoreactivity (COX-2-LI) in myenteric
      neurons. Half the neurons with COX-2-LI expressed nitric oxide synthase (NOS).
      COX-2-LI was not observed in smooth muscle cells. Interstitial cells of Cajal
      within muscle layers (IC-IM) expressed COX-2-LI, suggesting a novel role for IC
      IM. Molecular studies verified expression of COX-2 in gastric muscles.
      Quantitative polymerase chain reaction (PCR) showed equal expression of COX-1 and
      COX-2 in the antrum. COX-2 was more abundant in fundus. Indomethacin and
      GR253035X, a COX-2 inhibitor, increased antral phasic contractions and
      potentiated responses to ACh. Indomethacin, but not GR253035X, increased
      contractions and potentiated responses in tissues of COX-2 knockout mice.
      Indomethacin and GR253035X reduced tone in the fundus. CONCLUSIONS: COX-2 is
      constitutively expressed by IC-IM and neurons in the stomach and at levels
      similar to COX-1. Prostanoids produced by COX-2 regulate mechanical activities of
      fundus and antral muscles.

PMID- 11984530
TI  - Inactivation of the transcription factor Elf3 in mice results in dysmorphogenesis
      and altered differentiation of intestinal epithelium.
AB  - BACKGROUND & AIMS: The mammalian small intestine is lined by a highly specialized
      epithelium that functions in the digestion and absorption of nutrients. The
      molecular mechanisms that direct intestinal epithelial cell morphogenesis and
      terminal differentiation are poorly understood. We have previously identified
      Elf3 (E74-like factor-3) as a member of the ETS transcription factor family
      strongly expressed in small intestinal epithelium. The aim of this study is to
      investigate the biological roles of Elf3 in vivo. METHODS: Mice with a null
      mutation of Elf3 were generated through targeted gene disruption.
      Characterization of intestinal development was performed by histologic and
      immunohistochemical techniques. RESULTS: Targeted disruption of Elf3 resulted in
      fetal lethality of about 30% at around embryonic day 11.5. Seventy percent of the
      Elf3-deficent progeny were born and displayed severe alterations of tissue
      architecture in the small intestine, manifested by poor villus formation and
      abnormal morphogenesis and terminal differentiation of absorptive enterocytes and
      mucus-secreting goblet cells. Crypt cell proliferation, however, appeared intact
      in Elf3-deficient mice.Elf3-deficient enterocytes express markedly reduced levels
      of the transforming growth factor beta type II receptor (TGF-beta RII), an
      inducer of intestinal epithelial differentiation. CONCLUSIONS: Elf3 is an
      important regulator of morphogenesis and terminal differentiation of epithelial
      cell lineages in the small intestine.

PMID- 11984531
TI  - Novel genes and functional relationships in the adult mouse gastrointestinal
      tract identified by microarray analysis.
AB  - BACKGROUND & AIMS: A genome-level understanding of the molecular basis of
      segmental gene expression along the anterior-posterior (A-P) axis of the
      mammalian gastrointestinal (GI) tract is lacking. We hypothesized that functional
      patterning along the A-P axis of the GI tract could be defined at the molecular
      level by analyzing expression profiles of large numbers of genes. METHODS: Incyte
      GEM1 microarrays containing 8638 complementary DNAs (cDNAs) were used to define
      expression profiles in adult mouse stomach, duodenum, jejunum, ileum, cecum,
      proximal colon, and distal colon. Highly expressed cDNAs were classified based on
      segmental expression patterns and protein function. RESULTS: 571 cDNAs were
      expressed 2-fold higher than reference in at least 1 GI tissue. Most of these
      genes displayed sharp segmental expression boundaries, the majority of which were
      at anatomically defined locations. Boundaries were particularly striking for
      genes encoding proteins that function in intermediary metabolism, transport, and
      cell-cell communication. Genes with distinctive expression profiles were compared
      with mouse and human genomic sequence for promoter analysis and gene discovery.
      CONCLUSIONS: The anatomically defined organs of the GI tract (stomach, small
      intestine, colon) can be distinguished based on a genome-level analysis of gene
      expression profiles. However, distinctions between various regions of the small
      intestine and colon are much less striking. We have identified novel genes not
      previously known to be expressed in the adult GI tract. Identification of genes
      coordinately regulated along the A-P axis provides a basis for new insights and
      gene discovery relevant to GI development, differentiation, function, and
      disease.

PMID- 11984532
TI  - Bile acids regulate the ontogenic expression of ileal bile acid binding protein
      in the rat via the farnesoid X receptor.
AB  - BACKGROUND & AIMS: In the rat, an increase in ileal bile acid binding protein
      (IBABP) expression occurs during the third postnatal week. In vitro studies
      suggest that bile acids (BAs) increase IBABP transcription by activating the BA
      receptor, farnesoid X receptor (FXR). Thus, we investigated the role of BAs on
      the ontogenic expression of IBABP and whether FXR may mediate these effects.
      METHODS: Suckling rats were gavage-fed taurocholate for 3 days or were allowed to
      develop normally. Ileums were collected for Northern and Western blot analyses.
      Electrophoretic mobility shift assays for functional FXR were performed using
      nuclear extracts from ileums of both adult and developing rats. RESULTS:
      Taurocholate gavage significantly elevated IBABP messenger RNA and protein levels
      in suckling animals. Gelshift assays using adult ileal nuclear extracts incubated
      with a radiolabeled consensus inverted repeat-1 oligonucleotide (response element
      for FXR) revealed a high-molecular weight DNA/protein complex. Cold competition
      and supershift assays showed that this complex is sequence specific and confirmed
      that FXR is a component of the complex. Gelshift assays with nuclear extracts
      from rat ileum at different ages revealed absence of the DNA/protein complex in
      the second postnatal week when there is lack of IBABP expression and presence of
      these complexes at later ages when there is normally high expression. Western
      blot analyses showed FXR and its heterodimer partner, retinoid X receptor alpha,
      protein levels are low in the ileum during the suckling period and increase
      during the third postnatal week. CONCLUSIONS: BAs play a role in the normal
      developmental expression of IBABP through FXR activation, and decreased
      functional FXR in ileal nuclei during the suckling period may account, in part,
      for the lack of IBABP expression at this time.

PMID- 11984533
TI  - Familial gastrointestinal stromal tumors associated with dysphagia and novel type
      germline mutation of KIT gene.
AB  - A family with multiple gastrointestinal stromal tumors (GISTs), a new type of
      germline mutation of KIT gene, and dysphagia is reported. The mutation was
      observed at Asp-820 in tyrosine kinase (TK) II domain. Mutations in TK II domain
      have been found in mast cell and germ cell tumors but not in GISTs, and the
      present family members are the first reported cases of GISTs with TK II domain
      mutations, including sporadic GISTs. Because interleukin 3-dependent Ba/F3 murine
      lymphoid cells transfected with the mutant KIT complementary DNA grew
      autonomously without any growth factors and formed tumors in nude mice, the
      mutation was considered to be gain-of-function type. Family members with the
      germline KIT mutation reported dysphagia, but those without the mutation did not.
      The mechanism of dysphagia was examined with gastrointestinal fiberscopy,
      endoscopic ultrasonography, and esophageal manometry. No mechanical obstruction
      was found, and the esophagus was not remarkably dilated. In the family members
      with dysphagia, endoscopic ultrasonography at the esophagocardiac junction showed
      a thickened hyperechoic layer between the circular and longitudinal muscle
      layers, suggesting hyperplasia of interstitial cells of Cajal at the myenteric
      plexus layer. Manometry showed low resting lower esophageal sphincter pressure
      and abnormal simultaneous contractions of the esophagus without normal
      peristalsis. These findings indicate that the dysphagia of the present family is
      different from typical achalasia. This is the first report of familial dysphagia
      caused by germline gain-of-function mutation of the KIT gene at the TK II domain.

PMID- 11984534
TI  - The burden of selected digestive diseases in the United States.
AB  - BACKGROUND & AIMS: Gastrointestinal (GI) and liver diseases inflict a heavy
      economic burden. Although the burden is considerable, current and accessible
      information on the prevalence, morbidity, and cost is sparse. This study was
      undertaken to estimate the economic burden of GI and liver disease in the United
      States for use by policy makers, health care providers, and the public. METHODS:
      Data were extracted from a number of publicly available and proprietary national
      databases to determine the prevalence, direct costs, and indirect costs for 17
      selected GI and liver diseases. Indirect cost calculations were purposefully very
      conservative. These costs were compared with National Institutes of Health (NIH)
      research expenditures for selected GI and liver diseases. RESULTS: The most
      prevalent diseases were non-food-borne gastroenteritis (135 million cases/year),
      food-borne illness (76 million), gastroesophageal reflux disease (GERD; 19
      million), and irritable bowel syndrome (IBS; 15 million). The disease with the
      highest annual direct costs in the United States was GERD ($9.3 billion),
      followed by gallbladder disease ($5.8 billion), colorectal cancer ($4.8 billion),
      and peptic ulcer disease ($3.1 billion). The estimated direct costs for these 17
      diseases in 1998 dollars were $36.0 billion, with estimated indirect costs of
      $22.8 billion. The estimated direct costs for all digestive diseases were $85.5
      billion. Total NIH research expenditures were $676 million in 2000. CONCLUSIONS:
      GI and liver diseases exact heavy economic and social costs in the United States.
      Understanding the prevalence and costs of these diseases is important to help set
      priorities to reduce the burden of illness.

PMID- 11984536
TI  - Carcinogenesis at the gastroesophageal junction: free radicals at the frontier.

PMID- 11984537
TI  - Dyspepsia management in the millennium: the death of test and treat?

PMID- 11984538
TI  - Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis
      C.

PMID- 11984539
TI  - Leptin and liver fibrosis: a matter of fat.

PMID- 11984540
TI  - Angiotensin receptor antagonists in portal hypertension: fog over paradise.

PMID- 11984541
TI  - Discussion on randomized comparison of long-term losartan versus propranolol in
      lowering portal pressure in cirrhosis.

PMID- 11984542
TI  - Discussion on simultaneous intraesophageal impedance and pH measurement of acid
      and nonacid gastroesophageal reflux: effect of omeprazole.

PMID- 11984543
TI  - The human hepatocyte-specific organic anion transporter encoded by the SLC21A8
      gene.

PMID- 11984544
TI  - Does ursodeoxycholic acid cause lichenoid eruption?

PMID- 11984545
TI  - Tax-exempt terror?

PMID- 11984546
TI  - Animal welfare and scientific misconduct: reviewing, investigating, and reporting
      violations and concerns.

PMID- 11984547
TI  - To report or not to report?

PMID- 11984548
TI  - Epicorneal membrane on the eye of a Rex rabbit.

PMID- 11984550
TI  - Naked mole-rats: unique opportunities and husbandry challenges.
AB  - The naked mole-rat is a relative newcomer to biomedical and behavioral studies.
      The authors review this unusual rodent's uses in research, husbandry,
      reproduction, and common diseases.

PMID- 11984551
TI  - Husbandry and management of the domestic ferret.
AB  - Domesticated thousands of years ago and used for their hunting skills, ferrets
      have in more recent times proven to be excellent models for several fields of
      study, including virology and immunology. The author reviews the basic care and
      management of ferrets in the animal facility.

PMID- 11984552
TI  - Treating mites in a bat colony: a case study.
AB  - Since many bats used in research are wild-caught, dealing with mite infestation
      can present a unique challenge to the animal care staff. The authors tested the
      efficacy of fipronil spray for eliminating mites from a bat colony.

PMID- 11984553
TI  - Effect of body composition on isoflurane induction and recovery times in the
      meadow vole.
AB  - The inhalation anesthetic isoflurane is five times more soluble in lipid than in
      lean tissue. Using the meadow vole as a model, the authors sought to determine
      the effect of body composition on isoflurane induction and recovery times.

PMID- 11984554
TI  - Gene expression and cancer: getting it together.

PMID- 11984555
TI  - CHEKs and balances: accounting for breast cancer.

PMID- 11984556
TI  - Positioned to expand.

PMID- 11984557
TI  - Human mutation--blame (mostly) men.

PMID- 11984558
TI  - Translating the noise.

PMID- 11984561
TI  - GenMAPP, a new tool for viewing and analyzing microarray data on biological
      pathways.

PMID- 11984562
TI  - Polygenic susceptibility to breast cancer and implications for prevention.
AB  - The knowledge of human genetic variation that will come from the human genome
      sequence makes feasible a polygenic approach to disease prevention, in which it
      will be possible to identify individuals as susceptible by their genotype profile
      and to prevent disease by targeting interventions to those at risk. There is
      doubt, however, regarding the magnitude of these genetic effects and thus the
      potential to apply them to either individuals or populations. We have therefore
      examined the potential for prediction of risk based on common genetic variation
      using data from a population-based series of individuals with breast cancer. The
      data are compatible with a log-normal distribution of genetic risk in the
      population that is sufficiently wide to provide useful discrimination of high-
      and low-risk groups. Assuming all of the susceptibility genes could be
      identified, the half of the population at highest risk would account for 88% of
      all affected individuals. By contrast, if currently identified risk factors for
      breast cancer were used to stratify the population, the half of the population at
      highest risk would account for only 62% of all cases. These results suggest that
      the construction and use of genetic-risk profiles may provide significant
      improvements in the efficacy of population-based programs of intervention for
      cancers and other diseases.

PMID- 11984563
TI  - HIV maturation.

PMID- 11984564
TI  - Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of
      enzyme replacement.

PMID- 11984565
TI  - AIDS models: microbicides could learn from vaccines.

PMID- 11984566
TI  - Not just another researcher.

PMID- 11984567
TI  - Angiogenesis inhibitors revised and revived at AACR. American Association for
      Cancer Research.

PMID- 11984568
TI  - Smallpox vaccination becomes a social, financial...

PMID- 11984569
TI  - And political issue.

PMID- 11984570
TI  - Can WHO provide guidance on HIV drugs for developing countries?

PMID- 11984571
TI  - Gene therapy in recovery phase.

PMID- 11984572
TI  - Compromise for Australian ES cell research.

PMID- 11984573
TI  - Heartbeat clue to diagnosing vCJD.

PMID- 11984574
TI  - TSE threat to US increases.

PMID- 11984576
TI  - Training PhD researchers to translate science to clinical medicine: closing the
      gap from the other side.

PMID- 11984577
TI  - Emerging opportunities and career paths for the young physician-scientist.

PMID- 11984578
TI  - The other physician-scientist problem: where have all the young girls gone?

PMID- 11984580
TI  - New view at C.

PMID- 11984581
TI  - Nicotinic receptors: addiction's smoking gun?

PMID- 11984582
TI  - Gastric cancer gets the run-around.

PMID- 11984583
TI  - CREB family transcription factors inhibit neuronal suicide.

PMID- 11984584
TI  - An array of possibilities for multiple sclerosis.

PMID- 11984585
TI  - Corticosteroids and cardioprotection.

PMID- 11984586
TI  - Infectious triggers for inflammatory neurological diseases.

PMID- 11984587
TI  - No CaMK, no gain.

PMID- 11984589
TI  - ErbB2 is essential in the prevention of dilated cardiomyopathy.
AB  - Amplification of the gene encoding the ErbB2 (Her2/neu) receptor tyrosine kinase
      is critical for the progression of several forms of breast cancer. In a large
      scale clinical trial, treatment with Herceptin (trastuzumab), a humanized
      blocking antibody against ErbB2, led to marked improvement in survival. However,
      cardiomyopathy was uncovered as a mitigating side effect, thereby suggesting an
      important role for ErbB2 signaling as a modifier of human heart failure. To
      investigate the physiological role of ErbB2 signaling in the adult heart, we
      generated mice with a ventricular-restricted deletion of Erbb2. These ErbB2
      deficient conditional mutant mice were viable and displayed no overt phenotype.
      However, physiological analysis revealed the onset of multiple independent
      parameters of dilated cardiomyopathy, including chamber dilation, wall thinning
      and decreased contractility. Additionally, cardiomyocytes isolated from these
      conditional mutants were more susceptible to anthracycline toxicity. ErbB2
      signaling in cardiomyocytes is therefore essential for the prevention of dilated
      cardiomyopathy.

PMID- 11984590
TI  - Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1.
AB  - The inwardly rectifying K(+) channel Kir6.1 forms K(+) channels by coupling with
      a sulfonylurea receptor in reconstituted systems, but the physiological roles of
      Kir6.1-containing K(+) channels have not been determined. We report here that
      mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudden
      death associated with spontaneous ST elevation followed by atrioventricular block
      as seen on an electrocardiogram. The K(+) channel opener pinacidil did not induce
      K(+) currents in vascular smooth-muscle cells of Kir6.1-null mice, and there was
      no vasodilation response to pinacidil. The administration of methylergometrine, a
      vasoconstrictive agent, elicited ST elevation followed by cardiac death in Kir6.1
      null mice but not in wild-type mice, indicating a phenotype characterized by
      hypercontractility of coronary arteries and resembling Prinzmetal (or variant)
      angina in humans. The Kir6.1-containing K(+) channel is critical in the
      regulation of vascular tonus, especially in the coronary arteries, and its
      disruption may cause Prinzmetal angina.

PMID- 11984592
TI  - A pivotal role of cytosolic phospholipase A(2) in bleomycin-induced pulmonary
      fibrosis.
AB  - Pulmonary fibrosis is an interstitial disorder of the lung parenchyma whose
      mechanism is poorly understood. Potential mechanisms include the infiltration of
      inflammatory cells to the lungs and the generation of pro-inflammatory mediators.
      In particular, idiopathic pulmonary fibrosis is a progressive and fatal form of
      the disorder characterized by alveolar inflammation, fibroblast proliferation and
      collagen deposition. Here, we investigated the role of cytosolic phospholipase
      A(2) (cPLA(2)) in pulmonary fibrosis using cPLA(2)-null mutant mice, as cPLA(2)
      is a key enzyme in the generation of pro-inflammatory eicosanoids. Disruption of
      the gene encoding cPLA(2) (Pla2g4a) attenuated IPF and inflammation induced by
      bleomycin administration. Bleomycin-induced overproduction of thromboxanes and
      leukotrienes in lung was significantly reduced in cPLA(2)-null mice. Our data
      suggest that cPLA(2) has an important role in the pathogenesis of pulmonary
      fibrosis. The inhibition of cPLA(2)-initiated pathways might provide a novel
      therapeutic approach to pulmonary fibrosis, for which no pharmaceutical agents
      are currently available.

PMID- 11984591
TI  - Acute cardiovascular protective effects of corticosteroids are mediated by non
      transcriptional activation of endothelial nitric oxide synthase.
AB  - Corticosteroids have been shown to exert beneficial effects in the treatment of
      acute myocardial infarction, but the precise mechanisms underlying their
      protective effects are unknown. Here we show that high-dose corticosteroids exert
      cardiovascular protection through a novel mechanism involving the rapid, non
      transcriptional activation of endothelial nitric oxide synthase (eNOS). Binding
      of corticosteroids to the glucocorticoid receptor (GR) stimulated
      phosphatidylinositol 3-kinase and protein kinase Akt, leading to eNOS activation
      and nitric oxide dependent vasorelaxation. Acute administration of
      pharmacological concentrations of corticosteroids in mice led to decreased
      vascular inflammation and reduced myocardial infarct size following ischemia and
      reperfusion injury. These beneficial effects of corticosteroids were abolished by
      GR antagonists or eNOS inhibitors in wild-type mice and were completely absent in
      eNOS-deficient (Nos3(-/-)) mice. The rapid activation of eNOS by the non-nuclear
      actions of GR, therefore, represents an important cardiovascular protective
      effect of acute high-dose corticosteroid therapy.

PMID- 11984593
TI  - Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR
      protein in cystic fibrosis epithelial cells.
AB  - The most common mutation in cystic fibrosis, Delta F508, results in a cystic
      fibrosis transmembrane conductance regulator (CFTR) protein that is retained in
      the endoplasmic reticulum (ER). Retention is dependent upon chaperone proteins,
      many of which require Ca(++) for optimal activity. Interfering with chaperone
      activity by depleting ER Ca(++) stores might allow functional Delta F508-CFTR to
      reach the cell surface. We exposed several cystic fibrosis cell lines to the ER
      Ca(++) pump inhibitor thapsigargin and evaluated surface expression of Delta F508
      CFTR. Treatment released ER-retained Delta F508-CFTR to the plasma membrane,
      where it functioned effectively as a Cl(-) channel. Treatment with aerosolized
      calcium-pump inhibitors reversed the nasal epithelial potential defect observed
      in a mouse model of Delta F508-CFTR expression. Thus, ER calcium-pump inhibitors
      represent a potential target for correcting the cystic fibrosis defect.

PMID- 11984594
TI  - Acute phase cytotoxic T lymphocyte escape is a hallmark of simian
      immunodeficiency virus infection.
AB  - Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute
      HIV viremia. Despite two reports of CTL-resistant HIV variants emerging during
      acute infection, the contribution of acute CTL escape to HIV pathogenesis remains
      unclear. Difficulties inherent in studying acute HIV infection can be overcome by
      modeling virus-host interactions in SIV-infected rhesus macaques. We sequenced 21
      complete simian immunodeficiency virus (SIV)mac239 genomes at four weeks post
      infection to determine the extent of acute CTL escape. Here we show that viruses
      from 19 of 21 macaques escaped from CTLs during acute infection and that these
      escape-selecting CTLs were responsive to lower concentrations of peptide than
      other SIV-specific CTLs. Interestingly, CTLs that require low peptide
      concentrations for stimulation (high 'functional avidity') are particularly
      effective at controlling other viral infections. Our results suggest that acute
      viral escape from CTLs is a hallmark of SIV infection and that CTLs with high
      functional avidity can rapidly select for escape variants.

PMID- 11984595
TI  - Gene-microarray analysis of multiple sclerosis lesions yields new targets
      validated in autoimmune encephalomyelitis.
AB  - Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy
      revealed increased transcripts of genes encoding inflammatory cytokines,
      particularly interleukin-6 and -17, interferon-gamma and associated downstream
      pathways. Comparison of two poles of MS pathology--acute lesions with
      inflammation versus 'silent' lesions without inflammation--revealed
      differentially transcribed genes. Some products of these genes were chosen as
      targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice.
      Granulocyte colony-stimulating factor is upregulated in acute, but not in
      chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the
      acute phase, in contrast to knocking out the immunoglobulin Fc receptor common
      gamma chain where the effect is greatest on chronic disease. These results in EAE
      corroborate the microarray studies on MS lesions. Large-scale analysis of
      transcripts in MS lesions elucidates new aspects of pathology and opens
      possibilities for therapy.

PMID- 11984596
TI  - Autoimmunity due to molecular mimicry as a cause of neurological disease.
AB  - One hypothesis that couples infection with autoimmune disease is molecular
      mimicry. Molecular mimicry is characterized by an immune response to an
      environmental agent that cross-reacts with a host antigen, resulting in disease.
      This hypothesis has been implicated in the pathogenesis of diabetes, lupus and
      multiple sclerosis (MS). There is limited direct evidence linking causative
      agents with pathogenic immune reactions in these diseases. Our study establishes
      a clear link between viral infection, autoimmunity and neurological disease in
      humans. As a model for molecular mimicry, we studied patients with human T
      lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs.
      5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these
      antibodies would identify a central nervous system (CNS) autoantigen.
      Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear
      ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1
      cross-reacted with HTLV-1-tax, the immune response to which is associated with
      HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells,
      whose axons are preferentially damaged. Infusion of autoantibodies in brain
      sections inhibited neuronal firing, indicative of their pathogenic nature. These
      data demonstrate the importance of molecular mimicry between an infecting agent
      and hnRNP-A1 in autoimmune disease of the CNS.

PMID- 11984597
TI  - Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the
      brain and for perinatal survival.
AB  - The only proven requirement for ascorbic acid (vitamin C) is in preventing
      scurvy, presumably because it is a cofactor for hydroxylases required for post
      translational modifications that stabilize collagen. We have created mice
      deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of
      a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts
      from homozygous Slc23a1(-/-) mice had less than 5% of normal ascorbic-acid
      uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood
      and tissues of Slc23a1(-/-) mice. Prenatal supplementation of pregnant females
      did not elevate blood ascorbic acid in Slc23a1(-/-) fetuses, suggesting Slc23a1
      is important in placental ascorbic-acid transport. Slc23a1(-/-) mice died within
      a few minutes of birth with respiratory failure and intraparenchymal brain
      hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein
      B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since
      Slc23a1(-/-) mice showed no hemorrhage in any other tissues and their skin had
      normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We
      conclude that Slc23a1 is required for transport of ascorbic acid into many
      tissues and across the placenta. Deficiency of the transporter is lethal in
      newborn mice, thereby revealing a previously unrecognized requirement for
      ascorbic acid in the perinatal period.

PMID- 11984598
TI  - A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein
      inhibits Fc epsilon RI-mediated degranulation.
AB  - Human mast cells and basophils that express the high-affinity immunoglobulin E
      (IgE) receptor, Fc epsilon receptor 1 (Fc epsilon RI), have key roles in allergic
      diseases. Fc epsilon RI cross-linking stimulates the release of allergic
      mediators. Mast cells and basophils co-express Fc gamma RIIb, a low affinity
      receptor containing an immunoreceptor tyrosine-based inhibitory motif and whose
      co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivity.
      Here we designed, expressed and tested the human basophil and mast-cell
      inhibitory function of a novel chimeric fusion protein, whose structure is gamma
      Hinge-CH gamma 2-CH gamma 3-15aa linker-CH epsilon 2-CH epsilon 3-CH epsilon 4.
      This Fc gamma Fc epsilon fusion protein was expressed as the predicted 140-kappa
      D dimer that reacted with anti-human epsilon- and gamma-chain specific
      antibodies. Fc gamma Fc epsilon bound to both human Fc epsilon RI and Fc gamma
      RII. It also showed dose- and time-dependent inhibition of antigen-driven IgE
      mediated histamine release from fresh human basophils sensitized with IgE
      directed against NIP (4-hydroxy-3-iodo-5-nitrophenylacetyl). This was associated
      with altered Syk signaling. The fusion protein also showed increased inhibition
      of human anti-NP (4-hydroxy-3-nitrophenylacetyl) and anti-dansyl IgE-mediated
      passive cutaneous anaphylaxis in transgenic mice expressing human Fc epsilon RI
      alpha. Our results show that this chimeric protein is able to form complexes with
      both Fc epsilon RI and Fc gamma RII, and inhibit mast-cell and basophil function.
      This approach, using a Fc gamma Fc epsilon fusion protein to co-aggregate Fc
      epsilon RI with a receptor containing an immunoreceptor tyrosine-based inhibition
      motif, has therapeutic potential in IgE- and Fc epsilon RI-mediated diseases.

PMID- 11984599
TI  - Replication and compartmentalization of HIV-1 in kidney epithelium of patients
      with HIV-associated nephropathy.
AB  - HIV-associated nephropathy is a clinicopathologic entity that includes
      proteinuria, focal segmental glomerulosclerosis often of the collapsing variant,
      and microcystic tubulointerstitial disease. Increasing evidence supports a role
      for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated
      nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag
      and nef mRNA in renal epithelial cells of patients with HIV-associated
      nephropathy. Here, to investigate whether renal epithelial cells were
      productively infected by HIV-1, we examined renal tissue for the presence of HIV
      1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized
      the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells
      were removed by laser-capture microdissection from biopsies of two patients, DNA
      was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from
      individually dissected cells by nested PCR. Phylogenetic analysis of kidney
      derived sequences as well as corresponding sequences from peripheral blood
      mononuclear cells of the same patients revealed evidence of tissue-specific viral
      evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney
      derived sequences formed tissue-specific subclusters within the radiation of
      blood mononuclear cell-derived viral sequences from both patients. These data,
      along with the detection of HIV-1-specific proviral DNA and mRNA in tubular
      epithelium cells, argue strongly for localized replication of HIV-1 in the kidney
      and the existence of a renal viral reservoir.

PMID- 11984602
TI  - The microbial threat in fragile times: balancing known and unknown risks.

PMID- 11984600
TI  - Non-invasive in vivo monitoring of trackable viruses expressing soluble marker
      peptides.
AB  - Noninvasive methods are needed to study the kinetic properties of viruses in
      living organisms. Oncolytic viruses are used increasingly for cancer therapy but
      there is currently no satisfactory way to measure efficiency of tumor
      transduction, changing levels of viral gene expression or the timing of virus
      elimination. We therefore generated trackable oncolytic measles viruses
      expressing inert (nonimmunogenic, nonfunctional and accurately measurable)
      soluble marker peptides. The marker peptides did not compromise virus
      replication. Ex vivo and in vivo kinetics of the trackable viruses could be
      easily followed by measuring the concentrations of virally encoded marker
      peptides in culture supernatant or in serum. When mice bearing human tumor
      xenografts were challenged with the trackable viruses, distinct kinetic profiles
      of marker-gene expression could be correlated with distinct therapeutic outcomes.
      Oncolytic viruses expressing inert soluble marker polypeptides should greatly
      facilitate the rational development of effective, individually tailored cancer
      virotherapy.

PMID- 11984603
TI  - Reproductive tract infections: prevalence and risk factors in rural Bangladesh.
AB  - OBJECTIVE: To determine the prevalence of and risk factors for reproductive tract
      infections among men and women in a rural community in Bangladesh. METHODS: In
      the Matlab area a systematic sample of married non-pregnant women aged 15-50
      years was drawn from a comprehensive household registration system for married
      women. A systematic sample of married and unmarried men in the same age group was
      drawn from a census-derived demographic surveillance list. Private interviews
      were conducted with 804 women in a clinic, and cervical, vaginal, urinary and
      serological samples were collected. Urine and blood specimens were obtained from
      969 men who were interviewed at home. FINDINGS: The prevalence of bacterial and
      viral reproductive tract infections was low to moderate. For example, fewer than
      1% of the women had a cervical infection. No cases of human immunodeficiency
      virus (HIV) infection were found. However, among men there was a high level of
      reported risk behaviour and a low level of protection against infection.
      CONCLUSION: A low prevalence of reproductive tract infections, coupled with a
      high level of reported risk behaviour, indicated a need for primary programmes
      that would prevent an increase in the incidence of reproductive tract infections,
      sexually transmitted infections and HIV infection.

PMID- 11984604
TI  - Growth performance of affluent Indian children is similar to that in developed
      countries.
AB  - OBJECTIVE: A cross-sectional survey was conducted in order to determine whether
      an affluent population in south Delhi had a growth performance similar to that in
      developed countries and to identify socioeconomic factors that militated against
      optimal growth in this group. METHODS: The weights and lengths of 395 children
      aged 12-23 months and the heights of 331 mothers and 153 grandmothers were
      measured and information was obtained on family socioeconomic status and child
      feeding practices. Children born prematurely, i.e. before 37 weeks of gestation,
      and those with illness adversely affecting growth, were excluded from the
      analysis, as with the NCHS/WHO reference population. RESULTS: In 341 children
      included in the analysis, the mean Z-scores for weight-for-age, length-for-age
      and weight-for-length were -0.45, -0.28 and -0.32 respectively. About 6% of the
      children were underweight (weight-for-age Z-score < or =-2), 3% were stunted
      (length-for-age Z-score < or =-2), and 4% were wasted (weight-for-length Z-score
      < or =-2). The factors that were significantly associated with higher length-for
      age were one or both parents having 17 years or more of education (mean length
      for-age Z-score -0.17) and non-vegetarian diet (mean length-for-age Z-score -
      0.18). No socioeconomic factors were associated with mean weight-for-length.
      CONCLUSION: The children in this affluent population were close to the NCHS/WHO
      reference population with regard to anthropometric indicators. The subpopulation
      with higher parental education had even better growth. It is intended to include
      this subpopulation in the WHO Multicentre Growth Reference Study.

PMID- 11984605
TI  - Structure and performance of infectious disease surveillance and response, United
      Republic of Tanzania, 1998.
AB  - OBJECTIVE: To assess the structure and performance of and support for five
      infectious disease surveillance systems in the United Republic of Tanzania:
      Health Management Information System (HMIS); Infectious Disease Week Ending;
      Tuberculosis/Leprosy; Human Immunodeficiency Virus/Acquired Immunodeficiency
      Syndrome; and Acute Flaccid Paralysis/Poliomyelitis. METHODS: The systems were
      assessed by analysing the core activities of surveillance and response and
      support functions (provision of training, supervision, and resources). Data were
      collected using questionnaires that involved both interviews and observations at
      regional, district, and health facility levels in three of the 20 regions in the
      United Republic of Tanzania. FINDINGS: An HMIS was found at 26 of 32 health
      facilities (81%) surveyed and at all 14 regional and district medical offices.
      The four other surveillance systems were found at <20% of health facilities and
      <75% of medical offices. Standardized case definitions were used for only 3 of 21
      infectious diseases. Nineteen (73%) health facilities with HMIS had adequate
      supplies of forms; 9 (35%) reported on time; and 11 (42%) received supervision or
      feedback. Four (29%) medical offices with HMIS had population denominators to use
      for data analyses; 12 (86%) were involved in outbreak investigations; and 11
      (79%) had conducted community prevention activities. CONCLUSION: While HMIS could
      serve as the backbone for IDSR in the United Republic of Tanzania, this will
      require supervision, standardized case definitions, and improvements in the
      quality of reporting, analysis, and feedback.

PMID- 11984606
TI  - Preferences of urban Zimbabweans for health and life lived at different ages.
AB  - OBJECTIVE: To determine the age-weighting preferences of urban Zimbabweans in
      relation to health care priorities. METHOD: A total of 67 randomly selected
      residents of a high-density area of Harare participated in the study.
      Participants were asked "person trade-off" questions to determine their
      preferences in terms of the numbers of people of various ages who would be saved
      from death and from suffering a year of ill-health relative to the number of 30
      year-olds who would be saved from these eventualities. FINDINGS: The responses
      indicate that the value of averting a year of ill-health was judged greatest for
      15-year-olds and was equal for people aged 1, 30, and 45 years. The value of
      averting a death primarily reflected the expected years of life lost, but the
      influence of age-weighting was evident in that 15 years was the most highly
      valued age. CONCLUSION: Although the age-weighting curves did not correspond
      exactly with the Global Burden of Disease (GBD) age-weights, Zimbabweans showed a
      preference for saving the lives of young adults. The GBD age-weights should be
      used to determine the disability-adjusted life years lost in the Zimbabwean
      population.

PMID- 11984607
TI  - Vaccine-associated paralytic poliomyelitis in India during 1999: decreased risk
      despite massive use of oral polio vaccine.
AB  - OBJECTIVE: Vaccine-associated paralytic poliomyelitis (VAPP) is a rare but
      serious consequence of the administration of oral polio vaccine (OPV).
      Intensified OPV administration has reduced wild poliovirus transmission in India
      but VAPP is becoming a matter of concern. METHODS: We analysed acute flaccid
      paralysis (AFP) surveillance data in order to estimate the VAPP risk in this
      country. VAPP was defined as occurring in AFP cases with onset of paralysis in
      1999, residual weakness 60 days after onset, and isolation of vaccine-related
      poliovirus. Recipient VAPP cases were a subset with onset of paralysis between 4
      and 40 days after receipt of OPV. FINDINGS: A total of 181 AFP cases met the case
      definition. The following estimates of VAPP risk were made: overall risk, 1 case
      per 4.1 to 4.6 million OPV doses administered; recipient risk,1 case per 12.2
      million; first-dose recipient risk, 1 case per 2.8 million; and subsequent-dose
      recipient risk, 1 case per 13.9 million. CONCLUSION: On the basis of data from a
      highly sensitive surveillance system the estimated VAPP risk in India is
      evidently lower than that in other countries, notwithstanding the administration
      of multiple OPV doses to children in mass immunization campaigns.

PMID- 11984608
TI  - Interventions to reduce tuberculosis mortality and transmission in low- and
      middle-income countries.
AB  - Tuberculosis is among the top ten causes of global mortality and affects low
      income countries in particular. This paper examines, through a literature review,
      the impact of tuberculosis control measures on tuberculosis mortality and
      transmission, and constraints to scaling-up. It also provides estimates of the
      effectiveness of various interventions using a model proposed by Styblo. It
      concludes that treatment of smear-positive tuberculosis using the WHO directly
      observed treatment, short-course (DOTS) strategy has by far the highest impact.
      While BCG immunization reduces childhood tuberculosis mortality, its impact on
      tuberculosis transmission is probably minimal. Under specific conditions, an
      additional impact on mortality and transmission can be expected through treatment
      of smear-negative cases, intensification of case-finding for smear-positive
      tuberculosis, and preventive therapy among individuals with dual tuberculosis-HIV
      infection. Of these interventions, DOTS is the most cost-effective at around US$
      5-40 per disability-adjusted life year (DALY) gained. The cost for BCG
      immunization is likely to be under US$ 50 per DALY gained. Treatment of smear
      negative patients has a cost per DALY gained of up to US$ 100 in low-income
      countries, and up to US$ 400 in middle-income settings. Other interventions, such
      as preventive therapy for HIV-positive individuals, appear to be less cost
      effective. The major constraint to scaling up DOTS is lack of political
      commitment, resulting in shortages of funding and human resources for
      tuberculosis control. However, in recent years there have been encouraging signs
      of increasing political commitment. Other constraints are related to involvement
      of the private sector, health sector reform, management capacity of tuberculosis
      programmes, treatment delivery, and drug supply. Global tuberculosis control
      could benefit strongly from technical innovation, including the development of a
      vaccine giving good protection against smear-positive pulmonary tuberculosis in
      adults; simpler and shorter drug regimens for treatment of tuberculosis disease
      and infection; and improved diagnostics for tuberculosis infection and disease.

PMID- 11984609
TI  - A district-based audit of the causes and circumstances of maternal deaths in
      South Kalimantan, Indonesia.
AB  - A district-based audit of maternal and perinatal mortality began during 1994 in
      three provinces of South Kalimantan, Indonesia. Both medical and non-medical
      factors were documented and an effort was made to progress from merely assessing
      substandard care to recommending improvements in access to care and the quality
      of care. Extensive discussions of cases of maternal death were held during
      regular meetings with providers, policy-makers and community members. The sources
      of information included verbal autopsies with family members and medical records.
      Between 1995 and 1999 the audit reviewed 130 maternal deaths. The leading causes
      of death were haemorrhage (41%) and hypertensive diseases (32%). Delays in
      decision-making and poor quality of care in health facilities were seen as
      contributory factors in 77% and 60% of the deaths, respectively. Economic
      constraints were believed to have contributed to 37% of the deaths. The distance
      between a patient's home and a health provider or facility did not appear to have
      a significant influence, nor did transport problems. The audit led to changes in
      the quality of obstetric care in the district. Its success was particularly
      attributable to the process of accountability of both health providers and policy
      makers and to improved working relationships between health providers at
      different levels and between providers and the community. With a view to the
      continuation and further expansion of the audit it may be necessary to reconsider
      the role of the provincial team, the need of health providers for
      confidentiality, the added benefit of facility-based audits, the need to
      incorporate scientific evidence into the review process, and the possible
      consideration of severe complications as well as deaths. It may also be necessary
      to recognize that village midwives are not solely responsible for maternal
      deaths.

PMID- 11984610
TI  - Questionnaires for rapid screening of schistosomiasis in sub-Saharan Africa.
AB  - New initiatives are aiming to reduce the global burden of schistosomiasis, mainly
      through the large-scale application of chemotherapy. To target chemotherapy
      effectively, rapid assessment procedures are needed for identifying high-risk
      communities that are foci for the disease. In this review, we examine the
      development and validation of simple school questionnaires for screening
      communities for Schistosoma haematobium and S. mansoni rapidly and inexpensively.
      The focus is on sub-Saharan Africa, where 85% of the current schistosomiasis
      burden is concentrated. For more than a decade, the questionnaire approach has
      been validated in 10 countries, with 133 880 children interviewed in 1282
      schools, and with 54 996 children examined for S. haematobium. The questionnaires
      were well accepted, highly reliable, and of low cost. The success of the
      questionnaires is explained by the fact that S. haematobium infections were
      easily perceived through the presence of blood in urine. Evidence from 48 258
      children interviewed in 545 schools indicated that reported blood in stools and
      bloody diarrhoea are valuable indicators for community diagnosis of S. mansoni.
      However, the diagnostic performance of the questionnaires for S. mansoni was
      weaker than for S. haematobium, and although these results are encouraging, the
      questionnaires need additional validation. Recently, questionnaires were extended
      from community to individual diagnosis and showed considerable promise.
      Questionnaires are now available for promptly defining the magnitude of
      schistosomiasis in a large area, which will allow limited resources for morbidity
      control to be allocated optimally.

PMID- 11984611
TI  - Compression of morbidity and active ageing: key priorities for public health
      policy in the 21st century.

PMID- 11984612
TI  - Aging, natural death, and the compression of morbidity. 1980.

PMID- 11984613
TI  - The contribution of social science research to malaria prevention and control.

PMID- 11984614
TI  - Treat now--while we have the drugs: Interview by Robert Waldgate.

PMID- 11984615
TI  - Disinsection of aircraft.

PMID- 11984616
TI  - Rubella immunization strategies in the state of Sao Paulo, Brazil.

PMID- 11984617
TI  - Global Fund for AIDS, TB and malaria opens shop.

PMID- 11984618
TI  - Nurse and mother faces her own TB and HIV.

PMID- 11984624
TI  - Biological soil crusts in a xeric Florida shrubland: composition, abundance, and
      spatial heterogeneity of crusts with different disturbance histories.
AB  - Biological soil crusts consisting of algae, cyanobacteria, lichens, fungi,
      bacteria, and mosses are common in habitats where water and nutrients are limited
      and vascular plant cover is discontinuous. Crusts alter soil factors including
      water availability, nutrient content, and erosion susceptibility, and thus are
      likely to both directly and indirectly affect plants. To establish this link, we
      must first understand the crust landscape. We described the composition,
      abundance, and distribution of microalgae in crusts from a periodically burned,
      xeric Florida shrubland, with the goal of understanding the underlying
      variability they create for vascular plants, as well as the scale of that
      variability. This is the first comprehensive study of crusts in the southeastern
      United States, where the climate is mesic but sandy soils create xeric
      conditions. We found that crusts were both temporally and spatially heterogeneous
      in depth and species composition. For example, cyanobacteria and algae increased
      in abundance 10-15 years after fire and away from dominant shrubs. Chlorophyll a
      levels recovered rapidly from small-scale disturbance relative to intact crusts,
      but these disturbances added to crust patchiness. Plants less than 1 m apart can
      experience different crust environments that may alter plant fitness, plant
      interactions, and plant community composition.

PMID- 11984625
TI  - Temporal variation in community composition, pigmentation, and F(v)/F(m) of
      desert cyanobacterial soil crusts.
AB  - Summers on the Colorado Plateau (USA) are typified by harsh conditions such as
      high temperatures, brief soil hydration periods, and high UV and visible
      radiation. We investigated whether community composition, physiological status,
      and pigmentation might vary in biological soil crusts as a result of such
      conditions. Representative surface cores were sampled at the ENE, WSW, and top
      microaspects of 20 individual soil crust pedicels at a single site in Canyonlands
      National Park, Utah, in spring and fall of 1999. Frequency of cyanobacterial
      taxa, pigment concentrations, and dark adapted quantum yield [F(v)/F(m)] were
      measured for each core. The frequency of major cyanobacterial taxa was lower in
      the fall compared to spring. The less-pigmented cyanobacterium Microcoleus
      vaginatus showed significant mortality when not in the presence of Nostoc spp.
      and Scytonema myochrous (Dillw.) Agardh. (both synthesizers of UV radiation
      linked pigments) but had little or no mortality when these species were abundant.
      We hypothesize that the sunscreen pigments produced by Nostoc and Scytonema in
      the surface of crusts protect other, less-pigmented taxa. When fall and spring
      samples were compared, overall cyanobacterial frequency was lower in fall, while
      sunscreen pigment concentrations, chlorophyll a concentration, and F(v)/F(m) were
      higher in fall. The ratio of cyanobacterial frequency/chlorophyll a
      concentrations was 2-3 times lower in fall than spring. Because chlorophyll a is
      commonly used as a surrogate measure of soil cyanobacterial biomass, these
      results indicate that seasonality needs to be taken into consideration. In the
      fall sample, most pigments associated with UV radiation protection or repair were
      at their highest concentrations on pedicel tops and WSW microaspects, and at
      their lowest concentrations on ENE microaspects. We suggest that differential
      pigment concentrations between microaspects are induced by varying UV radiation
      dosage at the soil surface on these different microaspects.

PMID- 11984626
TI  - Immunological detection of Nitrospira-like bacteria in various soils.
AB  - Chemolithotrophic nitrite oxidizers were enriched from five different soils
      including freshwater marsh, permafrost, garden, agricultural, and desert soils
      and monitored during the cultivation procedure. Immunoblot analysis was used to
      identify the nitrite oxidizing organisms with monoclonal antibodies, which
      recognize the key enzyme of nitrite oxidation in a genus-specific reaction
      [Bartosch et al. (1999) Appl Environ Microbiol 65:4126-4133]. The morphological
      characteristics of the enriched nitrite oxidizers were additionally studied using
      transmission electron microscopy (TEM) and fluorescence microscopy. By means of
      the antibodies and TEM analysis Nitrospira could be clearly identified in
      enrichment cultures derived from freshwater marsh and from permafrost soil.
      Nitrospira cells were enriched simultaneously with cells of the genus Nitrobacter
      when nitrite concentrations of 0.2 g of NaNO2 L(-1) were used. However, in
      enrichment cultures containing 2 g of NaNO2 L(-1) Nitrobacter was exclusively
      detected. During fluorescence microscopic observations of DAPI stained samples
      microcolonies were found in enrichment cultures from freshwater marsh,
      permafrost, garden, and agricultural soil. They had a similar morphology to
      Nitrospira-like microcolonies from activated sludge. In conclusion, Nitrospira
      seems to be not only a common aquatic but also a usual soil bacterium.

PMID- 11984627
TI  - Eco-physiological characterization of soil bacterial populations in different
      states of growth.
AB  - The method based on characterization of microbial populations in terms of their
      growth rate in agar plates has been used for testing the prediction of the theory
      of r- and K-selection in a microbial community from a tropical soil. Conditions
      which could lead bacterial populations to grow exponentially or to enter into a
      stationary phase were obtained by growing soil microbial populations in a
      chemostat and in a chemostat with recycle, respectively. Significant differences
      in population distribution patterns were observed by comparing results from the
      two growth systems. When soil community was grown in a chemostat and subjected
      specifically to well-defined r- and K-conditions, stable associations of
      organisms with r- and K-type characteristics developed as a consequence of
      environmental pressure. In contrast, when cultivated in chemostat with recycle
      under the same r- and K-conditions imposed on chemostat cultures, distribution
      patterns of r- and K-selected populations appeared very little affected by
      changes in substrate availability.

PMID- 11984628
TI  - Characterization of Sphingomonas sp. Ant 17, an aromatic hydrocarbon-degrading
      bacterium isolated from Antarctic soil.
AB  - Sphingomonas sp. strain Ant 17 was isolated from fuel-contaminated soil collected
      at Scott Base, Ross Island, Antarctica. We anticipated that Ant 17 would be a
      good model organism for studying cold climate bioremediation, and therefore
      determined its biodegradation capabilities and tolerance of potentially growth
      limiting environmental conditions. Sphingomonas sp. Ant 17 degrades the aromatic
      fraction of several different crude oils, jet fuel, and diesel fuel at low
      temperatures and without nutrient amendment. It utilizes or transforms a broad
      range of pure aromatic substrates, including hydrocarbons, heterocycles, and
      aromatic acids and alcohols. Ant 17 grows at temperatures of 1 degree C to 35
      degrees C and mineralizes radiolabeled phenanthrene over a range of more than 24
      degrees C. This psychrotolerant isolate appears to utilize hydrocarbons more
      efficiently at low temperatures than would be predicted by mesophilic enzyme
      kinetics. The optimum pH for growth was 6.4 at 22 degrees C, with extended lag
      phases observed in more alkaline media. However, there was less effect of pH on
      lag phase at lower temperatures. Ant 17 displayed greater tolerance to UV
      irradiation and freeze-thaw cycles than the hydrocarbon-degrading isolate
      Sphingomonas sp. WPO-1, which may reflect adaptation to its Antarctic soil
      environment. However, it was more sensitive than expected to desiccation and to
      low concentrations of NaCl and CaCl(2). Ant 17 was phenotypically stable and
      lacked detectable plasmids, suggesting a chromosomal location for genes encoding
      aromatic degradation enzymes. Its broad aromatic substrate range and tolerance of
      low and fluctuating temperature and low nutrients make Sphingomonas sp. Ant 17 a
      valuable microbe for examining fuel spill bioremediation in cold soils.

PMID- 11984629
TI  - A cross-system comparison of bacterial and fungal biomass in detritus pools of
      headwater streams.
AB  - The absolute amount of microbial biomass and relative contribution of fungi and
      bacteria are expected to vary among types of organic matter (OM) within a stream
      and will vary among streams because of differences in organic matter quality and
      quantity. Common types of benthic detritus [leaves, small wood, and fine benthic
      organic matter (FBOM)] were sampled in 9 small (1st-3rd order) streams selected
      to represent a range of important controlling factors such as surrounding
      vegetation, detritus standing stocks, and water chemistry. Direct counts of
      bacteria and measurements of ergosterol (a fungal sterol) were used to describe
      variation in bacterial and fungal biomass. There were significant differences in
      bacterial abundance among types of organic matter with higher densities per unit
      mass of organic matter on fine particles relative to either leaves or wood
      surfaces. In contrast, ergosterol concentrations were significantly greater on
      leaves and wood, confirming the predominance of fungal biomass in these larger
      size classes. In general, bacterial abundance per unit organic matter was less
      variable than fungal biomass, suggesting bacteria will be a more predictable
      component of stream microbial communities. For 7 of the 9 streams, the standing
      stock of fine benthic organic matter was large enough that habitat-weighted reach
      scale bacterial biomass was equal to or greater than fungal biomass. The
      quantities of leaves and small wood varied among streams such that the relative
      contribution of reach-scale fungal biomass ranged from 10% to as much as 90% of
      microbial biomass. Ergosterol concentrations were positively associated with
      substrate C:N ratio while bacterial abundance was negatively correlated with C:N.
      Both these relationships are confounded by particle size, i.e., leaves and wood
      had higher C:N than fine benthic organic matter. There was a weak positive
      relationship between bacterial abundance and streamwater soluble reactive
      phosphorus concentration, but no apparent pattern between either bacteria or
      fungi and streamwater dissolved inorganic nitrogen. The variation in microbial
      biomass per unit organic matter and the relative abundance of different types of
      organic matter contributed equally to driving differences in total microbial
      biomass at the reach scale.

PMID- 11984630
TI  - Food web structure in the recently flooded Sep Reservoir as inferred from
      phytoplankton population dynamics and living microbial biomass.
AB  - Phytoplankton dynamics, bacterial standing stocks and living microbial biomass
      (derived from ATP measurements, 0.7-200 mm size class) were examined in 1996 in
      the newly flooded (1995) Sep Reservoir ('Massif Central,' France), for evidence
      of the importance of the microbial food web relative to the traditional food
      chain. Phosphate concentrations were low, N:P ratios were high, and phosphate
      losses converted into carbon accounted for <50% of phytoplankton biomass and
      production, indicating that P was limiting phytoplankton development during the
      study. The observed low availability of P contrasts with the high release of
      "directly" assimilable P often reported in newly flooded reservoirs, suggesting
      that factors determining nutrient dynamics in such ecosystems are complex. The
      phosphate availability, but also the water column stability, seemed to be among
      the major factors determining phytoplankton dynamics, as (i) large-size
      phytoplankton species were prominent during the period of increasing water column
      stability, whereas small-size species dominated phytoplankton assemblages during
      the period of decreasing stability, and (ii) a Dinobryon divergens bloom occurred
      during a period when inorganic P was undetectable, coinciding with the lowest
      values of bacterial standing stocks. Indication of grazing limitation of
      bacterial populations by the mixotrophic chrysophyte D. divergens (in late
      spring) and by other potential grazers (mainly rotifers in summer) seemed to be
      confirmed by the Model II or functional slopes of the bacterial vs phytoplankton
      regressions, which were always <0.63. Phytoplankton biomass was not correlated
      with phosphorus sources and its contribution was remarkably low relative to the
      living microbial biomass which, in contrast, was positively correlated with total
      phosphorus in summer. We conclude that planktonic microheterotrophs are strongly
      implicated in the phosphorus dynamics in the Sep Reservoir, and thus support the
      idea that an important amount of matter and energy flows through the "microbial
      loop" and food web, shortly after the flooding of a reservoir.

PMID- 11984631
TI  - Bacterial distribution and phylogenetic diversity in the Changjiang estuary
      before the construction of the Three Gorges Dam.
AB  - The bacterial community structure in the Changjiang estuary was studied for
      comparison with future changes, related to the construction of the Three Gorges
      Dam. Population densities of bacteria in the surface water at station C1
      estimated by CFU on marine agar plates and by DAPI direct count, were 2.8 x 10(4)
      ml(-1) and 4.2 x 10(5) ml(-1), respectively. Physicochemical properties of water,
      such as temperature and salinity, suggested that station C1 was affected by
      freshwater from the Changjiang River. Cluster analysis of the PCR-RFLP patterns
      obtained from 9 samples showed that the bacterial community structure at station
      C1 was different from the structure at the other stations. Bacterial diversity in
      the surface water at station C1 was studied based on the genotypes of the 250
      clones of 16S rRNA, and on the phenotypes generated on Biolog GN plates for 70
      isolates. Sequences of bacteria from two common marine groups, alpha- and gamma
      Proteobacteria, were frequently observed. Some other divisions, including the
      beta-Proteobacteria, C/F/B group, low G+C gram positive, high G+C gram positive,
      chloroplasts, and relatives of Verrucomicrobia were also observed. The putative
      dominant species based on both genotype and phenotype analyses were close
      relatives of Alteromonas macleodii or Roseobacter spp. These results reflected
      the nutrient-rich environment at station C1.

PMID- 11984632
TI  - Functional groups and activities of bacteria in a highly acidic volcanic mountain
      stream and lake in Patagonia, Argentina.
AB  - Acidic volcanic waters are naturally occurring extreme habitats that are subject
      of worldwide geochemical research but have been little investigated with respect
      to their biology. To fill this gap, the microbial ecology of a volcanic acidic
      river (pH approximately equal to 0-1.6), Rio Agrio, and the recipient lake
      Caviahue in Patagonia, Argentina, was studied. Water and sediment samples were
      investigated for Fe(II), Fe(III), methane, bacterial abundances, biomass, and
      activities (oxygen consumption, iron oxidation and reduction). The extremely
      acidic river showed a strong gradient of microbial life with increasing values
      downstream and few signs of life near the source. Only sulfide-oxidizing and
      fermentative bacteria could be cultured from the upper part of Rio Agrio.
      However, in the lower part of the system, microbial biomass and oxygen
      penetration and consumption in the sediment were comparable to non-extreme
      aquatic habitats. To characterize similarities and differences of chemically
      similar natural and man-made acidic waters, our findings were compared to those
      from acidic mining lakes in Germany. In the lower part of the river and the lake,
      numbers of iron and sulfur bacteria and total biomass in sediments were
      comparable to those known from acidic mining lakes. Bacterial abundance in water
      samples was also very similar for both types of acidic water (around 10(5) mL(
      1)). In contrast, Fe(II) oxidation and Fe(III) reduction potentials appeared to
      be lower despite higher biogenic oxygen consumption and higher photosynthetic
      activity at the sediment-water interface. Surprisingly, methanogenesis was
      detected in the presence of high sulfate concentrations in the profundal sediment
      of Lake Caviahue. In addition to supplementing microbiological knowledge on
      acidic volcanic waters, our study provides a new view of these extreme sites in
      the general context of aquatic habitats.

PMID- 11984633
TI  - Diversity of microcystin genes within a population of the toxic cyanobacterium
      Microcystis spp. in Lake Wannsee (Berlin, Germany).
AB  - In order to find out how many genotypes determine microcystin production of
      Microcystis spp. in field populations, single colonies (clones) were sampled from
      Lake Wannsee (Berlin, Germany), characterized morphologically, and subsequently
      analyzed by PCR for a region within the mcyB gene encoding the activation of one
      amino acid during microcystin biosynthesis. The different morphospecies varied
      considerably in the proportion of microcystin-producing genotypes. Most colonies
      (73%) of M. aeruginosa contained this gene whereas only 16% of the colonies
      assigned to M. ichthyoblabe and no colonies of M. wesenbergii gave a PCR product
      of the mcyB gene. Restriction fragment length polymorphism revealed seven
      restriction profiles showing low variability in nucleotide sequence within each
      restriction type (0.4-4%) and a low to high variability (1.6-38%) between
      restriction types. In addition, the sequences of amino acids within the mcyB gene
      were analyzed to compare the specificity of the amino acid activation during
      microcystin biosynthesis between restriction types and with the occurrence of
      amino acids in microcystin variants as detected by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Most of the microcystin
      producing colonies showed high similarity in the sequence of amino acids and
      contained microcystin-LR (LR refers to leucine and arginine in the variable
      positions of the heptapeptide), microcystin-RR, and microcystin-YR, as well as
      other variants in minor concentrations. It is concluded that the gene product
      found for most of the microcystin-producing colonies in the lake is rather
      unspecific and the diversity of microcystin variants in the lake results from
      activation of various amino acids during microcystin biosynthesis in the same
      genotypes.

PMID- 11984634
TI  - Longitudinal and vertical trends of bacterial limitation by phosphorus and carbon
      in the Mediterranean Sea.
AB  - The effect of phosphate (P), nitrate (N), and organic carbon (C, glucose)
      enrichment on heterotrophic bacterial production was examined along two
      longitudinal transects covering the whole Mediterranean Sea during June and
      September 1999. During these cruises, integrated bacterial production ranged from
      11 to 349 mgC m(-2) d(-1) for the 0-150 m layer. P was found to stimulate
      bacterial production (BP) in 13 out of 18 experiments, in the eastern and in the
      western Mediterranean Sea. Organic carbon stimulation of bacterial production was
      observed at two stations in the Alboran Sea, where the highest bacterial
      production was recorded (216 and 349 mg C m(-2) d(-1)) and in the Sicily Strait.
      Maximum rates of alkaline phosphatase (AP) increased from the Alboran to the
      Levantine Sea whereas AP turnover time decreased. Moreover, alkaline phosphatase
      activity was not systematically reduced following additions of P. In cases of P
      limitation, however, the alkaline phosphatase activity to bacterial production
      ratio was severely reduced in the P and NPC enrichments. Generally, the addition
      of the limiting factor--whether P or C--had a synchronous stimulating effect on
      bacterial production and ectoaminopeptidase activity and induced a decline in the
      amino acid respiration percentage. At two selected stations in the eastern and
      northwestern Mediterranean, response to enrichment was tested on vertical
      profiles. Bacteria shifted from P to C limitation at a depth where soluble
      reactive phosphorus was still undetectable, but corresponding to a strong
      increase in alkaline phosphatase turnover time. Our results showed that values of
      AP turnover time lower than 100 h corresponded to situations of P limitation of
      bacterial production.

PMID- 11984635
TI  - Specific 16S rDNA sequences associated with naphthalene degradation under sulfate
      reducing conditions in harbor sediments.
AB  - Previous studies have demonstrated that naphthalene and other polycyclic aromatic
      hydrocarbons (PAHs) can be anaerobically oxidized with the reduction of sulfate
      in PAH-contaminated marine harbor sediments, including those in San Diego Bay. In
      order to learn more about the microorganisms that might be involved in anaerobic
      naphthalene degradation, the microorganisms associated with naphthalene
      degradation in San Diego Bay sediments were evaluated. A dilution-to-extinction
      enrichment culture strategy, designed to recover the most numerous culturable
      naphthalene-degrading sulfate reducers, resulted in the enrichment of
      microorganisms with 16S rDNA sequences in the d-Proteobacteria, which were
      closely related to a previously described pure culture of a naphthalene-degrading
      sulfate reducer, NaphS2, isolated from sediments in Germany. A more traditional
      enrichment culture approach, expected to enrich for the fastest-growing
      naphthalene-degrading sulfate reducers, yielded 16S rDNA sequences closely
      related to those found in the dilution-to-extinction enrichments and NaphS2.
      Analysis of 16S rDNA sequences in sediments from two sites in San Diego Bay that
      had been adapted for rapid naphthalene degradation by continual amendment with
      low levels of naphthalene suggested that the microbial community composition in
      the amended sediments differed from that present in the unamended sediments from
      the same sites. Most significantly, 6-8% of the sequences recovered from 100
      clones of each of the naphthalene-amended sediments were closely related to the
      16S rDNA sequences in the enrichment cultures as well as the sequence of the pure
      culture, NaphS2. No sequences in this NaphS2 phylotype were recovered from the
      sediments that were not continually exposed to naphthalene. A PCR primer, which
      was designed based on these phylotype sequences, was used to amplify additional
      16S rDNA sequences belonging to the NaphS2 phylotype from PAH-degrading sediments
      from Island End River (Boston), MA, and Liepaja Harbor, Latvia. Closely related
      sequences were also recovered from highly contaminated sediment from Tampa Bay,
      FL. These results suggest that microorganisms closely related to NaphS2 might be
      involved in naphthalene degradation in harbor sediments. This finding contrasts
      with the frequent observation that the environmentally relevant microorganisms
      cannot be readily recovered in pure culture and suggests that further study of
      the physiology of NaphS2 may provide insights into factors controlling the rate
      and extent of naphthalene degradation in marine harbor sediments.

PMID- 11984636
TI  - Lactobacillic acid accumulation in the plasma membrane of Oenococcus oeni: a
      response to ethanol stress?
AB  - It is known that ethanol strongly interferes with the development and activity of
      lactic acid bacteria in wine. In this work, it was observed that membrane
      composition was dependent of ethanol concentration and cell physiological state.
      The protein electrophoretic profile was modified in the membranes of Oenococcus
      oeni cultured in presence of 8 and 10% ethanol. Concerning the membrane lipid
      composition, it was observed that O. oeni maintained a high level of phospholipid
      biosynthesis via the relative increased biosynthesis of phosphoethanolamine and
      sphingomyelin in presence of ethanol. On the other hand, ethanol induced an
      increase in the membrane lactobacillic acid percentage at the expense of cis
      vaccenic acid. This increased synthesis of lactobacillic acid appears as the more
      significant change induced by ethanol in O. oeni membrane. The increase of
      lactobacillic acid in the membrane of O. oeni clearly appears as a factor that
      provides protection against the toxic effect of ethanol, balancing the increase
      of membrane fluidity normally attributed to ethanol. The results presented in
      this paper constitute evidence that lactobacillic acid may have a part in the
      survival and or adaptive mechanisms developed by O. oeni under culture adverse
      conditions, allowing these bacteria to maintain their activity in the presence of
      ethanol, namely performing malolactic fermentation in wine.

PMID- 11984637
TI  - Enrichment of autotrophic anaerobic ammonium-oxidizing consortia from various
      wastewaters.
AB  - The option for biological nitrogen removal has recently been broadened with the
      description of simultaneous nitrification/denitrification, anaerobic ammonium
      oxidation (ANAMMOX) and the concept of CANON (completely autotrophic nitrogen
      removal over nitrite). An autotrophic anaerobic ammonium oxidation (AAAO)
      consortium was successfully selected and enriched from municipal treatment plant
      sludges in Sydney, Australia, but not from industrial coke-oven wastewater
      sludges. Chemolithoautotrophic basic salt (CLABS) medium was used in the
      selection of AAAO organisms and chloramphenicol was added to the initial stage of
      selection to eliminate denitrifiers. Two different temperatures, 37 degrees C and
      55 degrees C, were used in the selection of mesophilic and thermophilic
      consortia, respectively. Thermophilic AAAO organisms were not selected at 55
      degrees C. Mesophilic AAAO activities, however, were evident in both batch and
      continuous cultures, whereby ammonium was consumed concurrently with a decrease
      of nitrite, giving a ratio of 1:1-1:1.3 in ammonium removal rate over nitrite
      consumption rate. A continuous-mode mesophilic fixed-bed reactor was established
      to enrich the AAAO consortium. After 1 year, biofilms, pinkish in color, had
      developed on the support media and side wall of the feed-line tubing. Ammonium
      and nitrite consumption increased from approximately 15 mg to 60 mg d(-1) L(-1)
      over a period of 243 days. Later, transmission electron microscopy (TEM) and
      fluorescence in situ hybridization (FISH) techniques revealed that the dominant
      cell type in the AAAO consortium had a similar morphology and 16S rDNA sequence
      homology to that of the recently described ANAMMOX organism, "Brocadia
      anammoxidans".

PMID- 11984638
TI  - A dilution technique for the direct measurement of viral production: a comparison
      in stratified and tidally mixed coastal waters.
AB  - The abundance of heterotrophic bacteria and viruses, as well as rates of viral
      production and virus-mediated mortality, were measured in Discovery Passage and
      the Strait of Georgia (British Columbia, Canada) along a gradient of tidal mixing
      ranging from well mixed to stratified. The abundances of bacteria and viruses
      were approximately 10(6) and 10(7) mL(-1), respectively, independent of mixing
      regime. Viral production estimates, monitored by a dilution technique,
      demonstrated that new viruses were produced at rates of 10(6) and 10(7) mL(-1)h(
      1) across the different mixing regimes. Using an estimated burst size of 50
      viruses per lytic event, ca. 19 to 27% of the standing stock of bacteria at the
      stratified stations and 46 to 137% at the deep-mixed stations were removed by
      viruses. The results suggest that mixing of stratified waters during tidal
      exchange enhances virus-mediated bacterial lysis. Consequently, viral lysis
      recycled a greater proportion of the organic carbon required for bacterial growth
      under non-steady-state compared to steady-state conditions.

PMID- 11984639
TI  - Algal extracellular products suppress Anabaena flos-aquae heterocyst spacing.
AB  - Intra- and interspecific chemical signals allow bacteria to respond to
      environmental conditions by regulating gene transcription. In cyanobacteria, gene
      products and the presence of fixed nitrogen regulate heterocyst frequency. In
      this paper, we describe a chemical made by a green alga, Chlamydomonas
      reinhardtii, that suppresses heterocyst formation in the co-occurring
      cyanobacterium, Anabaena flos-aquae. Cyanobacterial heterocyst frequencies were
      reduced in the presence of water-soluble, proteinase- and heat-resistant
      molecules greater than 15 kDa in molecular size. Green algal cells in all phases
      of growth made the suppressor. Ammonium and nitrate concentrations in the medium
      did not correlate with this change in phenotype. In addition, growth rate was not
      enhanced by the extracellular products. Therefore, C. reinhardtii extracellular
      products acted as a heterocyst inhibitor, not as a fixed nitrogen source.
      Chemical interactions between green algae and cyanobacteria influence heterocyst
      formation, an important consideration in understanding the outcome of competition
      between these organisms and the dynamics of phytoplankton communities.

PMID- 11984640
TI  - Microhabitats and chemical microenvironments under saxicolous lichens growing on
      granite.
AB  - Lasallia hispanica, Parmelia omphalodes, and Cornicularia normoerica, saxicolous
      thalli growing on granite, show a close relationship with other lichens and
      microorganisms living in the lithic substrate beneath them. The lithobiontic
      community is an accumulation of microorganisms at an interface forming a biofilm,
      which interacts with the lithic substrate both geophysically and geochemically.
      Because of their fruticose and foliose morphology, the saxicolous species
      examined here are mainly involved in geophysical processes, but in the proximity
      of their attachment structures, geochemical processes may also be observed. On
      the other hand, fungi, algae and cyanobacteria forming crustose lichens, as well
      as free-living lithobiontic microorganisms, are known to show combined
      geophysical and geochemical action, mainly on laminar minerals. The substrate
      zone where the saxicolous lichens are attached is most affected by weathering
      reactions and shows the highest co-occurrence of lithobiontic microorganisms. The
      physical and chemical properties of the substrate, along with lichen and
      microorganism activity, determine different microenvironments and microhabitats.
      The ecological functioning of these lithobiontic communities is not yet fully
      understood, and research efforts similar to the present are needed to confirm
      that their development is influenced by interrelations between different
      community members and the substrate, as suggested here.

PMID- 11984641
TI  - A Lotka-Volterra competition model and its global convergence to a definite axial
      equilibrium.
AB  - We consider a four-species model based on competition and show that the whole
      four-species system collapses to a definite single species equilibrium at its
      carrying capacity. To do so, we use the results of Hirsch, Van Den Driessche and
      Zeeman, Hofbauer and Sigmund, and the product theorem of the Conley connection
      matrix theory by Mischaikow and Reineck.

PMID- 11984642
TI  - Homoclinic solutions in mechanical systems with small dissipation. Application to
      DNA dynamics.
AB  - This paper analyzes the problem of persistence of homoclinic solutions to
      perturbed systems of second order ODE's. These systems arise from PDE's, when
      considering solutions in the form of travelling waves. It is shown that
      homoclinic solutions persist in the presence of dissipation. Dissipation can be
      balanced by nonautonomous terms of compact support, which are controlled by a
      single parameter. This result is applied to prove the existence of torsional
      pulse-like travelling waves propagating along a nonelastic DNA molecule. In this
      case the energy is added to system by advancing the RNA polymerase.

PMID- 11984643
TI  - Regularity in irregular echinoids.
AB  - Using the mathematical concept of eutactic star, we prove that it is possible to
      define a morphospace for irregular echinoids by using a single parameter. In
      particular, we have found an extraordinary geometric property in the flower-like
      patterns of the five ambulacral petals of these animals. This property is
      fulfilled with great accuracy for a large collection of fossil specimens and
      provides new insights in the study of the viable skeletal designs of extinct
      and/or living organisms.

PMID- 11984644
TI  - Analysing protein energy data by a stochastic model for cooperative interactions:
      comparison and characterization of cooperativity.
AB  - In the frame of a Markov chain model for cooperative interactions in proteins,
      previously introduced by us, we deal here with estimation of unknown parameters
      from protein energy data. One of these parameters characterizes the cooperativity
      of a protein; we propose to measure it also by the so-called approximate entropy.
      By our computations the approximate entropy turns out to be a decreasing function
      of the cooperativity. We analyse both simulated data of the Markov chain, and
      protein energy data obtained by molecular dynamics simulation. Moreover, we
      compare two rubredoxin proteins at different temperatures, according to their
      degrees of cooperativity.

PMID- 11984645
TI  - Vessel distensibility and flow distribution in vascular trees.
AB  - In a class of model vascular trees having distensible blood vessels, we prove
      that flow partitioning throughout the tree remains constant, independent of the
      nonzero driving flow (or nonzero inlet to terminal outlet pressure difference).
      Underlying assumptions are: (1) every vessel in the tree exhibits the same
      distensibility relationship given by D/D(0) = f(P) where D is the diameter which
      results from distending pressure P and D(0) is the diameter of the individual
      vessel at zero pressure (each vessel may have its own individual D(0). The choice
      of f(P) includes distensibilities often used in vessel biomechanics modeling,
      e.g., f(P) = 1 + alpha P or f(P) = b + (1-b) exp(-c P), as well as f(P) which
      exhibit autoregulatory behavior. (2) Every terminal vessel in the tree is
      subjected to the same terminal outlet pressure. (3) Bernoulli effects are
      ignored. (4) Flow is nonpulsatile. (5) Blood viscosity within any individual
      vessel is constant. The results imply that for a vascular tree consistent with
      assumptions 2-5, the flow distribution calculations based on a rigid geometry,
      e.g., D=D(0), also gives the flow distribution when assuming the common
      distensibility relationships.

PMID- 11984646
TI  - Fitness versus longevity in age-structured population dynamics.
AB  - We examine the dynamics of an age-structured population model in which the life
      expectancy of an offspring may be mutated with respect to that of the parent.
      While the total population of the system always reaches a steady state, the
      fitness and age characteristics exhibit counter-intuitive behavior as a function
      of the mutational bias. By analytical and numerical study of the underlying rate
      equations, we show that if deleterious mutations are favored, the average fitness
      of the population reaches a steady state, while the average population age is a
      decreasing function of the average fitness. When advantageous mutations are
      favored, the average population fitness grows linearly with time t, while the
      average age is independent of the average fitness. For no mutational bias, the
      average fitness grows as t2/3.

PMID- 11984647
TI  - A method for estimating torque-vector directions of shoulder muscles using
      surface EMGs.
AB  - In this study, a new method is proposed to estimate the torque-vector directions
      of each shoulder muscle. The method is based on a multiple regression model that
      reconstructs shoulder torque, which is calculated from the hand force and
      posture, from the surface EMG of many muscles recorded simultaneously. The torque
      vector directions of eleven shoulder muscles of four subjects were obtained at up
      to 30 different arm postures with this method. The mean confidence interval ( p<
      0.05) of the estimated torque-vector direction of each subject was 7.7-10.6
      degrees. The correlation coefficient between the measured shoulder torque and
      reconstructed shoulder torque was between 0.76-0.84. The results for majority of
      the muscles were in accordance with previous studies, and reasonable from the
      viewpoint of anatomy. The torque-vector directions of a muscle, which are
      estimated with this method, have more of a functional meaning than a pure
      anatomical or mechanical one. These indicate the direction of the shoulder torque
      accompanying the muscle activation for a normal shoulder action that involves the
      cooperative contraction of many muscles.

PMID- 11984648
TI  - Detecting determinism in short time series, with an application to the analysis
      of a stationary EEG recording.
AB  - We have developed a new method for detecting determinism in a short time series
      and used this method to examine whether a stationary EEG is deterministic or
      stochastic. The method is based on the observation that the trajectory of a time
      series generated from a differentiable dynamical system behaves smoothly in an
      embedded phase space. The angles between two successive directional vectors in
      the trajectory reconstructed from a time series at a minimum embedding dimension
      were calculated as a function of time. We measured the irregularity of the angle
      variations obtained from the time series using second-order difference plots and
      central tendency measures, and compared these values with those from surrogate
      data. The ability of the proposed method to distinguish between chaotic and
      stochastic dynamics is demonstrated through a number of simulated time series,
      including data from Lorenz, Rossler, and Van der Pol attractors, high-dimensional
      equations, and 1/f noise. We then applied this method to the analysis of
      stationary segments of EEG recordings consisting of 750 data points (6-s
      segments) from five normal subjects. The stationary EEG segments were not found
      to exhibit deterministic components. This method can be used to analyze
      determinism in short time series, such as those from physiological recordings,
      that can be modeled using differentiable dynamical processes.

PMID- 11984649
TI  - Dynamics and stability of legged locomotion in the horizontal plane: a test case
      using insects.
AB  - Motivated by experimental studies of insects, we propose a model for legged
      locomotion in the horizontal plane. A three-degree-of freedom, energetically
      conservative, rigid-body model with a pair of compliant virtual legs in
      intermittent contact with the ground allows us to study how dynamics depends on
      parameters such as mass, moment of inertia, leg stiffness, and length. We find
      periodic gaits, and show that mechanics alone can confer asymptotic stability of
      relative heading and body angular velocity. We discuss the relevance of our
      idealized models to experiments and simulations on insect running, showing that
      their gait and force characteristics match observations reasonably well. We
      perform parameter studies and suggest that our model is relevant to the
      understanding of locomotion dynamics across species.

PMID- 11984650
TI  - Analysis of short- and long-term effects of adaptation in human postural control.
AB  - The short-term (i.e., days) and long-term (i.e., months) effects of adaptation to
      posturography examinations were investigated in 12 normal subjects who were
      repeatedly examined for five consecutive days and again after 90 days. The
      examinations were conducted both with eyes open and closed, and the perturbations
      were evoked by a pseudorandomly applied vibration stimulation to the calf
      muscles. The evoked anteroposterior responses were analyzed with a method
      considering adaptation in the slow changes in posture and in the stimulus
      response relationship. Repetition of examinations on a daily basis revealed a
      gradual improvement of postural-control performance. The body sway induced by the
      stimulation was significantly reduced and the dynamical properties changed. Most
      of the improvements remained after 90 days, but some parameters such as the
      complexity of the control system used were increased to the initial level. The
      results confirm previous observations that postural control contains several
      partially independent adaptive processes, observed in terms of alteration of
      posture and as a progressive reduction of body sway induced by stimulation. The
      method used for the adaptation analysis in this study could be applied to analyze
      biological systems with multiple individual adaptive processes with different
      time courses or characteristics, or where the adaptation processes are related to
      multiple internal or external factors.

PMID- 11984651
TI  - New attractor states for synchronous activity in synfire chains with excitatory
      and inhibitory coupling.
AB  - In a feedforward network of integrate-and-fire neurons, where the firing of each
      layer is synchronous (synfire chain), the final firing state of the network
      converges to two attractor states: either a full activation or complete fading of
      the tailing layers. In this article, we analyze various modes of pattern
      propagation in a synfire chain with random connection weights and delta-type
      postsynaptic currents. We predict analytically that when the input is fully
      synchronized and the network is noise free, varying the characteristics of the
      weights distribution would result in modes of behavior that are different from
      those described in the literature. These are convergence to fixed points, limit
      cycles, multiple periodic, and possibly chaotic dynamics. We checked our analytic
      results by computer simulation of the network, and showed that the above results
      can be generalized when the input is asynchronous and neurons are spontaneously
      active at low rates.

PMID- 11984652
TI  - A model of the cerebellar pathways applied to the control of a single-joint robot
      arm actuated by McKibben artificial muscles.
AB  - This article describes an expanded version of a previously proposed motor control
      scheme, based on rules for combining sensory and motor signals within the central
      nervous system. Classical control elements of the previous cybernetic circuit
      were replaced by artificial neural network modules having an architecture based
      on the connectivity of the cerebellar cortex, and whose functioning is regulated
      by reinforcement learning. The resulting model was then applied to the motion
      control of a mechanical, single-joint robot arm actuated by two McKibben
      artificial muscles. Various biologically plausible learning schemes were studied
      using both simulations and experiments. After learning, the model was able to
      accurately pilot the movements of the robot arm, both in velocity and position.

PMID- 11984653
TI  - Nonlinear dynamics of the EEG separated by independent component analysis after
      sound and light stimulation.
AB  - The electroencephalogram (EEG) is a multiscaled signal consisting of several time
      series components each with different dominant frequency ranges and different
      origins. Nonlinear measures of the EEG reflect the complexity of the overall EEG,
      but not of each component in it. The aim of this study is to examine effect of
      the sound and light (SL) stimulation on the complexity of each component of the
      EEG. We used independent component analysis to obtain independent components of
      the EEG. The first positive Lyapunov exponent (L1) was estimated as a nonlinear
      measure of complexity. Twelve subjects were administered photic and auditory
      stimuli with a frequency of 10 Hz, which corresponded to the alpha frequency of
      the EEG, by a sound and light entrainment device. We compared the L1 values of
      the EEGs and their independent components between baseline and after the SL
      stimulation. We detected that the L1 values of the EEG decreased after the SL
      stimulation in all channels except C3 and F4, indicating that the complexity of
      the EEG decreased. We showed that alpha components increased in proportion but
      decreased in complexity after the SL stimulation. The beta independent components
      were found to decrease in proportion and complexity. These results suggest that
      decreased complexity of the EEG after the SL stimulation may be principally
      caused by decreased complexity and increased proportion of the alpha independent
      components. We showed also that theta components increased in complexity after
      the SL stimulation. We propose that nonlinear dynamical analysis combined with
      independent component analysis may be helpful in understanding the temporal
      characteristics of the EEG, which cannot be detected by conventional linear or
      nonlinear methods.

PMID- 11984654
TI  - White-noise stimulation of the Hodgkin-Huxley model.
AB  - We studied the combined influence of noise and constant current stimulations on
      the Hodgkin-Huxley neuron model through time and frequency analysis of the
      membrane-potential dynamics. We observed that, in agreement with experimental
      data (Guttman et al. 1974), at low noise and low constant current stimulation the
      behavior of the model is well approximated by that of the linearized Hodgkin
      Huxley system. Conversely, nonlinearities due to firing dominate at large noise
      or current stimulations. The transition between the two regimes is abrupt, and
      takes place in the same range of noise and current intensities as the noise
      induced transition characterized by the qualitative change in the stationary
      distribution of the membrane potential (Tanabe and Pakdaman 2001a). The
      implications of these results are discussed.

PMID- 11984655
TI  - Increased rates of pulmonary metastases following sham laparotomy compared to CO2
      pneumoperitoneum and the inhibition of metastases utilizing perioperative
      immunomodulation and a tumor vaccine.
AB  - BACKGROUND: Subcutaneous tumor growth and establishment is increased after
      laparotomy; significantly smaller increases have been noted after
      CO2pneumoperitoneum (CO2 pneumo). Less is known about the impact of surgery on
      the fate of blood borne tumor cells. The extent of surgical abdominal wall trauma
      also correlates with the extent of early postoperative immunosuppression and the
      inflammatory response. These changes may favor lung metastases (mets) formation.
      This study's hypotheses were: (a) a reduction in surgical trauma or (b) a
      perioperative (periop) tumor vaccine or nonspecific immune up-regulation would
      limit lung mets formation. An intravenous tumor cell injection lung met model was
      used to test these hypotheses. METHODS: Study 1 determined the incidence of lung
      mets after sham laparotomy (OP) and CO2 pneumo. Three groups were studied
      (n=25/group) : Anesthesia control (AC), CO2 pneumo, and OP. 1 x 105 TA3Haushka
      adenocarcinoma cells were inoculated via tail vein injection into all mice
      immediately after surgery. Study 2 determined the impact of perioperative
      immunomodulation on lung mets formation. Five groups were studied (n=20/group) :
      AC, OP, OP + Monophosphoryl Lipid A (MPLA), OP + lysed tumor cells (LTC), or OP +
      MPLA + LTC. The vaccine consisted of 5 x 105 lysed TA3Ha tumor cells (LTC) and
      was given 5 times preop and once postop to the vaccine groups. MPLA, the nontoxic
      moiety of lipopolysaccharide, was used both as a vaccine adjuvant in the OP +
      MPLA + LTC group and as a nonspecific perioperative immune up-regulator in the OP
      + MPLA group. Five periop injections of MPLA were given to the OP + MPLA group.
      All mice were given tail vein injections of tumor cells after surgery. Fourteen
      days after surgery all mice were sacrificed, the lungs transected en bloc, and
      India ink injected into the trachea. The lungs were placed in Fekete's solution
      to counterstain the tumor foci white. The number of surface lung metastases was
      determined by two blinded observers, separately. RESULTS: In Study 1, there were
      significantly more lung tumors in the OP group (median=31.5) than the AC group
      (median=9; p<0.05) or the CO2 Pneumo group (median=6.5; p<0.05). There were no
      significant differences in the number of metastases between the AC and the CO2
      Pneumo groups or in the incidence of animals in each group with 1 or more lung
      mets. In Study 2 significantly fewer metastases were noted for the Op + LTC group
      (median=3; p<0.05) and the OP + LTC + MPLA group (median=0; p<0.05) when compared
      to the OP group (median=20). Although the OP + MPLA group mice had fewer
      metastases (median=4) than the OP group, this difference was not significant.
      Significantly fewer of the OP + LTC + MPLA group mice developed one or more lung
      tumors than in the OP, OP + MPLA, and the OP + LTC groups. CONCLUSIONS: Full sham
      laparotomy was associated with more postoperative lung metastases than CO2 pneumo
      or anesthesia alone in this murine model. Up-regulation of the immune system in
      the perioperative period with lysed tumor cells, alone or in combination with
      MPLA, resulted in significantly fewer postoperative lung metastases. MPLA alone
      resulted in a less marked reduction of lung metastases.

PMID- 11984656
TI  - Early small bowel obstruction complicating hand-assisted laparoscopic donor
      nephrectomy: an uncommon etiology.
AB  - Laparoscopic donor nephrectomy is gaining widespread acceptance as a minimally
      invasive technique for kidney donation. Although it has been associated with
      decreased patient morbidity and more rapid recovery, it exposes patients to
      possible complications inherent in its transperitoneal route. We report a case of
      a small bowel obstruction secondary to midjejunal intussusception occurring on
      the third postoperative day after a hand-assisted laparoscopic donor nephrectomy.
      The intussusception proved to be idiopathic since no lead point was identified.
      The patient recovered without significant sequela after reduction of the
      intussusceptum. Postoperative ideopathic intussusception is an uncommon cause of
      bowel obstruction in adults. Surgeons that perform laparoscopic donor nephrectomy
      will need to remain vigilant for complications that can be associated with the
      intraperitoneal route of this technique.

PMID- 11984657
TI  - Laparoscopic renal biopsy in bilateral pelvic kidney with chronic
      glomerulonephritis.
AB  - Percutaneous needle biopsy under the guidance of ultrasound or computerized
      tomography is the most valuable method in the diagnosis of parenchymal kidney
      diseases. However, sometimes it can be difficult to perform in the presence of
      certain anomalies, anatomic variations, or medical problems. In the presence of
      bilateral pelvic kidney, which is a rare anomaly, laparoscopy can be used to
      obtain biopsy. Biopsy of kidney was planned in a 26-year-old woman who presented
      with a history of hypertension for 7 years and proteinuria with the diagnosis of
      nephrotic syndrome. For the biopsy, the laparoscopic approach was chosen since
      the patient had bilateral pelvic kidneys. Under general anesthesia, using three
      port sites, the right kidney was reached, which was located more anterior than
      the left one. Three biopsy specimens for histologic evaluation were taken with a
      Tru-Cut biopsy needle. No complications were encountered during or after the
      operation. The patient was ceased from urological follow-up after performing an
      ultrasound on the first postoperative day. This is the first case of pelvic
      kidney with chronic glomerulonephritis reported in the literature in which the
      histologic diagnosis was made with the help of laparoscopy. Laparoscopic kidney
      biopsy is a minimally invasive technique that can be done in cases with anatomic
      variations, making percutaneous needle biopsy impossible.

PMID- 11984658
TI  - Primary pancreatic lymphoma.
AB  - Primary pancreatic lymphoma (PPL) is a rare form of extranodal lymphoma (less
      than 0.5% of pancreatic tumors) originating from the pancreatic parenchyma.
      Histopathological examination is usually mandatory to obtain a definitive
      diagnosis since symptoms and radiological features are quite similar to those of
      other pancreatic masses. Percutaneous fine-needle aspiration (FNA) of the
      pancreas requires experienced cytopathologists as well as advanced
      immunohistochemical assays to obtain a final diagnosis on a small amount of
      tissue. A 46-year-old man complaining of watery diarrhea and severe weight loss
      (more than 20 kg) for more than 1 year was admitted to our hospital due to severe
      diabetic crisis. Enlarged lymph nodes (2.5 x 1 cm) were found at the right
      axillary stations. Abdominal ultrasound revealed the presence of a large
      hyperechogenic mass, mainly located at the pancreatic head. Abdominal computed
      tomography scan confirmed a diffuse enlargement of the head and body of the
      pancreas associated with lymphadenopathy along the lesser gastric curvature.
      Percutaneous ultrasound-guided FNA of the pancreas as well as gross biopsy of the
      axillary lymph nodes were unable to identify the nature of the mass. Diagnostic
      laparoscopy was performed: several enlarged lymph nodes along the lesser gastric
      curvature were revealed. Multiple biopsies of the pancreatic head were taken and
      lymphadenectomy along the lesser curvature and the hepatic hilus was also
      performed. The definitive histopathological examination of the pancreatic
      specimen revealed a primary low-grade non-Hodgkin B cell pancreatic lymphoma. The
      postoperative course was unremarkable; the patient underwent systemic
      chemotherapy regime for low-grade B cell Hodgkin lymphoma and he was symptom free
      at 9-month follow-up.

PMID- 11984659
TI  - Ambulatory laparoscopic repair of inferior lumbar or Petit hernia: a case report.
AB  - Lumbar hernias are an uncommon variety of abdominal wall defect. Diagnosis
      depends largely on the capacity for clinical suspicion, and confirmation is based
      on imaging tests. Surgical treatment is controversial due to difficulty in
      defining the borders of the lumbar defect and the involvement of a bone margin.
      We present a case of traumatic lumbar hernia in the Petit triangle, diagnosed by
      computed tomography (CT) and repaired laparoscopically as a major ambulatory
      surgery procedure. The laparoscopic approach enabled us to identify the whole of
      the lumbar area and effect a profound reconstruction on the same side as the
      defect.

PMID- 11984661
TI  - Austrian experiences of antireflux surgery.
AB  - BACKGROUND: Antireflux surgery (ARS) is a well established treatment for GERD
      (gastroesophageal reflux disease). The present study gives an overview of
      experience in Austria regarding the frequency of open and laparoscopic ARS and
      how Austrian departments meet the requirements for surgery. METHODS: A
      questionnaire was sent to 115 surgical departments in Austria to evaluate in how
      many institutions antireflux surgery (open and/or laparoscopically) was performed
      since 1990, and which pre- and postoperative tests were obligatory, optional, or
      not performed. Units were divided into specialized and nonspecialized. RESULTS:
      The laparoscopic approach has gained in importance by about 300% in the past 5
      years in the few hospitals performing this procedure. Esophageal manometry and 24
      h pH monitoring were rarely done in nonspecialized units, despite the fact that
      GERD is mainly a functional disorder of the esophagus and stomach. In contrast to
      the nonspecialized units, the specialized unit performed upper endoscopy,
      esophageal manometry and 24-h esophageal pH monitoring as obligatory tests.
      CONCLUSIONS: ARS, both open and laparoscopic, is not commonly performed in
      surgical departments in Austria but the frequency has significantly increased in
      recent years. Laparoscopic ARS is a safe procedure in hospitals performing this
      frequently. Laparoscopic ARS should only be performed in specialized units with
      significant experience in gastroesophageal diseases, where functional testing of
      the esophagus can be done.

PMID- 11984662
TI  - Laparoscopic diaphragmatic hernia repair.
AB  - BACKGROUND: Adult-congenital diaphragmatic hernias and chronic traumatic
      diaphragmatic hernias are uncommon entities that are often technically
      challenging to repair. There is growing experience with a minimal access approach
      to these defects. METHODS: We reviewed the English-language literature using a
      MEDLINE search for "diaphragmatic hernia" and "laparoscopy." RESULTS: We found 19
      case reports of laparoscopic adult-congenital diaphragmatic hernia repair.
      Reported complications included two enterotomies, one of which required
      conversion to laparotomy. We also found 11 case reports of laparoscopic chronic
      traumatic diaphragmatic hernia repair, with no reported complications or
      recurrences. Average operative time was 98 min, and average length of stay was
      4.5 days. All reports claimed that there was less postoperative pain and an
      earlier return to full activity with the laparoscopic approach. Herein we discuss
      anatomy, pathophysiology, diagnosis, method of repair, and recurrence.
      CONCLUSION: Adult-congenital diaphragmatic hernia and chronic traumatic
      diaphragmatic hernia are amenable to laparoscopic repair. Although experience is
      still limited, laparoscopic repair appears safe and is associated with a shorter
      hospital stay.

PMID- 11984663
TI  - Retroperitoneoscopic nephropexy for symptomatic nephroptosis.
AB  - BACKGROUND: Open nephropexy for nephroptosis creates significant morbidity. We
      describe our technique for retroperitoneoscopic nephropexy and evaluate its
      efficacy. METHODS: Twenty-five renal units in 23 patients with symptomatic
      nephroptosis underwent retroperitoneoscopic nephropexy by suturing the posterior
      renal capsules and transfixing them to the back muscles. The diagnosis and
      postoperative assessment were made by typical symptoms (via patient
      questionnaire) and findings of intravenous urography (IVU) when the position was
      changed from supine to erect. RESULTS: Mean operative time was 188 min (range, 90
      330). Mean narcotic use was 15.6 mg morphine. Complete resolution of symptoms
      occurred in 84% (21/25) renal units; 12% (three of 25) achieved partial
      improvement (>75% decrease of preoperative symptoms). Follow-up IVU showed that
      88% of patients had a renal descent of <2 cm on standing; the others had a
      descent of 2-4 cm. All of the five renal units with hydronephrosis resolved
      completely after the operation. CONCLUSIONS: This modified technique of
      retroperitoneoscopic nephropexy is a minimally invasive, feasible, and highly
      successful option for treating patients with symptomatic nephroptosis.

PMID- 11984664
TI  - Symptomatic and physiologic outcomes after operative treatment for
      extraesophageal reflux.
AB  - BACKGROUND: Pharyngeal pH monitoring has recently been used to identify patients
      with extraesophageal symptoms induced by gastroesophageal reflux. We employed
      this method of acid detection to evaluate patients with respiratory symptoms
      prior to and after laparoscopic Nissen fundoplication to further elucidate the
      relationship between GERD and respiratory symptoms. METHODS: Twenty-one
      consecutive patients with extraesophageal symptoms thought to be caused by reflux
      underwent symptomatic and functional evaluation (esophageal manometry and 24-h pH
      monitoring with a pharyngeal probe) before and after laparoscopic Nissen
      fundoplication. Episodes of pharyngeal acid exposure were considered abnormal if
      the pH dropped below 4, occurred simultaneously with esophageal acidification,
      and occurred outside meal times. RESULTS: All patients had gastroesophageal
      reflux disease (GERD) and respiratory symptoms; nine of 15 (60%) had evidence of
      pharyngeal reflux preoperatively. Antireflux procedures resulted in a significant
      decrease in pharyngeal reflux (7.9 to 1.6 episodes/24h; p <0.05) and esophageal
      acid exposure (7.5% to 2.1%; p <0.05). In patients with pharyngeal reflux and
      complete postoperative testing, three (60%) obtained improvement of respiratory
      symptoms and resolution of pharyngeal reflux. In two patients with recurrent
      respiratory symptoms after surgery, persistent pharyngeal reflux was detected.
      CONCLUSION: Operative treatment of GERD is effective in controlling
      extraesophageal reflux, measured subjectively and objectively. Evidence of
      pharyngeal reflux on pH testing helps to identify which patients with respiratory
      symptoms will benefit from an antireflux procedure.

PMID- 11984666
TI  - Laparoscopic splenectomy using Ligasure. Preliminary experience.
AB  - BACKGROUND: Intraoperative bleeding is the main complication and main cause of
      conversion during laparoscopic splenectomy (LS). We present the advantages of the
      use of the Ligasure Vessel Sealing System added to lateral approach for achieving
      a safe vascular control. METHODS: Ligasure is an energy-based device which works
      applying a precise amount of bipolar energy and pressure to the tissue, achieving
      a permanent seal. We have performed a total of 35 LS in a 5-year period using
      different approaches and methods of dissection, including the anterior approach,
      monopolar coagulation, clips, endostaplers, and ultrasonic shears. In the last 10
      patients (4 males and 6 females, mean age 24 yr) we employed a technique with 4
      trocars, right semilateral position associated with the entire dissection of the
      spleen and vessels sealing (lower pole vessels, main vascular pedicles, short
      gastric vessels) performed with Ligasure. Six had thrombocytopenic idiopatic
      purpura (ITP), 2 hereditary spherocytosis and one each b-thalassemia and
      hemolytic anemia. RESULTS: Nine LS were completed with one (10%) conversion
      because of hilar bleeding due to accidental injury with Ligasure. The average
      splenic weight was 485 g (range 265-1800), with an average diameter of 16 cm
      (range 12-25). In all but one patients (the converted one) the intraoperative
      blood loss was less than 100 mL (range 50-100 mL, average 80 mL). No blood
      transfusion were needed. The average operative time was 120 min (range 90-165),
      including 2 patients undergoing combined laparoscopic cholecystectomy. There was
      no mortality, with one (10%) postoperative complication (thrombosis of the spleno
      portal axis), treated with a conservative approach. The average postoperative
      hospital stay was 3.5 days (range 3-6). CONCLUSIONS: The use of Ligasure,
      associated with the lateral position, results in a gain of time and safety.
      Furthermore, the average intraoperative bleeding of this series is very low.

PMID- 11984667
TI  - The duration of hemodynamic depression during laparoscopic cholecystectomy.
AB  - BACKGROUND: We previously evaluated the effects of pneumoperitoneum and patient
      position on hemodynamics during laparoscopic cholecystectomy and found that
      patient position had no effect on cardiac index (CI), stroke volume (SV), and
      left ventricular end diastolic volume (LVEDV). Analysis of that data showed that
      the hemodynamic depression associated with pneumoperitoneum was transient with
      values trending toward baseline during the operative period. The purpose of this
      study was to examine the duration of the adverse hemodynamic effects of
      pneumoperitoneum during laparoscopic cholecystectomy. METHODS: Thirty-eight
      patients undergoing laparoscopic cholecystectomy by a single surgeon were
      enrolled in the study. Hemodynamic data was collected via a transthoracic
      bioimpedance monitor. Baseline readings were taken prior to establishing
      pneumoperitoneum. Data was then collected continuously over the course of each
      case. Patients were compared to their baseline values. Data was analyzed every 5
      min with the paired t-test used to determine statistical significance. RESULTS:
      All parameters were compared to baseline values. Baseline was defined as 5 min
      after the induction of anesthesia. With insufflation to 15 mmHg CO2, CI fell from
      a baseline value of 2.82 L/min/m2 to 2.66 L/min/m2 (p = 0.04), SV from 71.58 mL
      to 65.44 mL (p = 0.002), and LVEDV from 111.46 mL to 102.68 mL (p = 0.003). At 5
      min, all values were further depressed. At 10 min all values were no longer
      significantly different from baseline. Values returned to baseline at 15 min and
      did not walver for the remainder of each case or the next 35 min. CONCLUSION:
      Patients undergoing laparoscopic cholecystectomy experience significant
      hemodynamic depression with pneumoperitoneum. These changes are short-lived and
      lose their statistical significance at 10 min from the time a patient undergoes
      pneumoperitoneum.

PMID- 11984669
TI  - Effects of carbon dioxide pneumoperitoneum on hemodynamics in cirrhotic rats.
AB  - BACKGROUND: The aim of our study was to investigate the effect of carbon dioxide
      pneumoperitoneum on systemic and splanchnic hemodynamics in cirrhotic rats.
      METHODS: Sprague-Dawley rats (n = 80) were used in this study. Liver cirrhosis
      was induced by thioacetamide administration intraperitoneally (200 mg/kg body
      weight, twice a week for 16 weeks). The radioactive microsphere method was used
      to measure systemic and regional hemodynamic parameters before, 1 h after the
      start, and 1 h after the release of pneumoperitoneum. RESULTS: Splanchnic blood
      flow and cardiac index were significantly depressed during pneumoperitoneum in
      liver cirrhosis and control groups, but no significant differences were seen
      between the two groups. In both groups, portal venous inflow decreased and
      hepatic arterial blood flow increased significantly during pneumoperitoneum.
      However, during pneumoperitoneum, total hepatic blood flow as a percentage of its
      value before pneumoperitoneum was lower in cirrhotic rats (71.0%) than in control
      rats (91.9%) (p <0.05, Mann-Whitney U-test). CONCLUSIONS: Carbon dioxide
      pneumoperitoneum markedly decreases total hepatic blood flow in cirrhotic rats
      due to the impaired hepatic arterial buffer response. Liver function should be
      carefully controlled in cirrhotic patients after laparoscopic surgery with
      pneumoperitoneum.

PMID- 11984670
TI  - Complications due to gallstones lost during laparoscopic cholecystectomy.
AB  - BACKGROUND: The aim of this study was to identify predisposing factors for
      complications after gallstone spillage during laparoscopic cholecystectomy (LC).
      METHODS: Papers derived from Medline search and papers from reference lists
      within these papers were studied. Ninety-one reports on complications caused by
      lost gallstones published between 1991 and 1998 were analyzed. These patients
      were compared with cases in published series on LC in general. RESULTS:
      Gallbladder perforation (20%) and stone spillage (9%) were the two most common
      complications of LC which occurred during the dissection (75%) and removal (25%)
      of the gallbladder. Predisposing factors for developing complications after stone
      spillage were: older age, male sex, acute cholecystitis, spillage of pigment
      stones, number of stones (>15) or size of the stone (O > 1.5 cm), and perihepatic
      localization of lost stones. CT-scan and ultrasound examination proved best for
      the recognition of complications caused by lost stones. Explorative laparotomy
      and surgical removal of the stones was the most frequently used therapy.
      CONCLUSIONS: Gallbladder perforation and stone spillage might cause hazardous
      complications. In cases with loss of numerous or large pigment stones which
      cannot be retrieved by laparoscopy, intraoperative conversion to open surgery can
      be justified.

PMID- 11984671
TI  - Grasping and dissecting instrument for hand-assisted laparoscopic surgery:
      development and early clinical experience.
AB  - BACKGROUND: The operative potential of hand-assisted laparoscopic surgery (HALS)
      could be enhanced by the introduction of a new generation of assisting
      instruments. These tools will have to meet specific requirements of shape,
      function, and safety of use. METHODS: Problems related to the working environment
      of HALS and deriving projectual restrictions of HALS instruments were analyzed in
      order to develop and manufacture a working prototype with grasping and dissecting
      properties to assist during HALS procedures. The resulting instrument was
      mechanically and clinically tested in 22 HALS procedures. RESULTS: The additional
      benefit of the new device was particularly appreciated during dissection and
      isolation of vascular pedicles (nephrectomies and splenectomies). It was shown to
      be safe and effective in providing the additional assistance it was designed for.
      CONCLUSION: The described grasping and dissecting instrument for HALS is of great
      value in assisting the surgeon during fine dissection, as required in selected
      procedures. New generation of HALS instruments should comply with the functional
      and safety issues analyzed in this report.

PMID- 11984672
TI  - Is laparoscopic left pancreatic resection justified?
AB  - BACKGROUND: We reviewed our experience of laparoscopic left pancreatectomy to
      establish the feasibility of this approach and the characteristics of the
      operating procedure. METHODS: Thirteen patients with a mean age of 60 years were
      deemed for a left pancreatectomy. Preoperative diagnoses were: nine mucinous
      cystadenoma and one insulinoma, intraductal mucinous ectasia, chronic
      pancreatitis with ductal stenosis, and distal pancreatic tumor. RESULTS:
      Operative mortality was nil. Two patients required conversion for bleeding from
      splenic vein injuries leading to a splenectomy in one case. The spleen was
      preserved in 10 cases. Postoperative course was uneventful in nine cases. Four
      patients experienced postoperative complications: one pancreatic fistula, two
      liquid cysts on the pancreatic margin, and one reoperation for bleeding from a
      trocar port. Length of stay ranged from 5 to 22 days. CONCLUSION: These
      preliminary results confirm that in selected cases laparoscopic resection of the
      left pancreas is feasible and safe.

PMID- 11984673
TI  - Power spectral analysis of heart rate variability during positive pressure
      pneumoperitoneum: the significance of increased cardiac sympathetic expression.
AB  - BACKGROUND: Positive pressure pneumoperitoneum (PPP) effects on the autonomic
      nervous system (ANS) might be of clinical importance, as imbalance in the
      autonomic cardiac control might lead to serious consequences. METHODS: Fifteen
      healthy patients undergoing elective laparoscopic cholecystectomy were analyzed
      for cardiac autonomic nervous activity by spectral heart rate variability, during
      awake state, before and after intubation, during CO2 PPP (14 mmHg), and after CO2
      evacuation. The very low, low, high and very high frequency (VLF, LF, HF, VHF
      respectively) bands of the spectral density of the heart rate variability (HRV)
      and their normalized values, as well as the LF/HF ratio, were obtained from the
      power spectra of R-R intervals, using the fast-Fourier transformation algorithm.
      RESULTS: Using Friedman's nonparametric test, only the difference between the
      power of LF during anesthesia (median 30.74) and the middle of PPP (median
      195.66) was found to be significant (p<0.012). Such change was recorded in 14
      patients (p = 0.001, sign test). CONCLUSIONS: Increased LF power reflects
      sympathetic cardiac activation. As the LF range accounts for regulation of blood
      pressure and baroreflex, several mechanisms may explain this activation. This in
      turn may predispose patients who suffer from cardiac disease to higher risk of
      developing ventricular arrhythmias, besides the possible adverse hemodynamic
      consequences of PPP.

PMID- 11984674
TI  - Elective laparoscopic colonic resection for diverticular disease: results of a
      multicenter study in 179 patients.
AB  - BACKGROUND: We undertook a retrospective multicenter study of elective
      laparoscopic sigmoidectomy for diverticulitis in order to assess the safety and
      the results of the procedure performed by a large number of surgeons. MATERIALS
      AND METHODS: Between January 1998 and April 1999, the French Society of
      Laparoscopic Surgery recruited retrospectively 179 patients from 10 surgical
      units, operated on for elective laparoscopic sigmoidectomy. There were 94 men and
      85 women with a mean age of 58 years (range, 30-82). The indications for surgery
      were acute attacks in 123 cases, complicated diverticulitis in 47 cases, and
      miscellaneous in 9 cases. RESULTS: The performed procedure was a successful
      laparoscopic assisted sigmoidectomy in 154 cases (with totally intracorporeal
      anastomosis in 136 cases and hand-sewn anastomosis via small incision in 18
      cases). The mean operation time was 223 min +/- 79 (range, 100-480). There was no
      mortality and 23 complications occurred in 23 patients (14.9%). Postoperative
      ileus lasted 2.5 +/- 0.9 days (range, 1-6), and oral intake started after 3.3 +/-
      1.3 days (range, 1-12). The mean postoperative stay was 9.3 days (range, 4-50).
      Conversion to laparotomy was necessary in 25 cases (13.9%). The essential causes
      of conversion were obesity, severe adhesions, and colonic inflammation. The mean
      postoperative stay for the 25 converted patients was 13 +/- 8.5 days (range, 7
      42). CONCLUSION: Elective laparoscopic sigmoidectomy for diverticulitis is
      feasible and is safe. The complication and mortality rates are similar to those
      observed after open procedures. For experienced surgical teams, laparoscopic
      colonic resection is a good approach for selected patients suffering from
      symptomatic diverticulitis.

PMID- 11984675
TI  - Laparoscopic cholecystectomy: are patients with biliary pancreatitis at increased
      operative risk?
AB  - BACKGROUND: Previous reports of laparoscopic cholecystectomy (LC) in patients
      with biliary pancreatitis suggested increased operative difficulty, high rates of
      conversion, and greater morbidity and mortality. METHODS: Between 1990 and 1997,
      LC was performed for biliary pancreatitis in 63 patients (Group I) and for other
      causes in 829 patients (Group II). RESULTS: Patients with biliary pancreatitis
      were significantly older (median age 57 vs 50 years, p = 0.009), with greater co
      morbidity (ASA III/IV 24% vs 11%, p = 0.008). The groups were comparable with
      respect to the frequency of previous abdominal operations, acute inflammation of
      the gallbladder, and the frequency of bile duct calculi detected by
      intraoperative cholangiography. Moderate to severe adhesions involving the
      gallbladder were significantly more frequent in patients with biliary
      pancreatitis (46% vs 29%, p = 0.004). No significant differences were observed
      between the two groups with respect to intraoperative (1.5% Group I vs 6.0% Group
      II, p = 0.109) or postoperative complications (10% vs 8%, p = 0.426), conversion
      rate (0 vs 2.7%, p = 0.181), or duration of operation (median 92 vs 85 min, p =
      0.33). CONCLUSION: Despite increased age and co-morbidity and more frequent
      adhesions, our data showed no evidence that intraoperative or postoperative
      complications were more frequent in patients with biliary pancreatitis than in
      other patients undergoing LC.

PMID- 11984676
TI  - Laparoscopic options in the treatment of splenic artery aneurysms.
AB  - BACKGROUND: The retrogastric and often intrapancreatic position of splenic artery
      aneurysms (SAA) has discouraged many surgeons from attempting the laparoscopic
      resection of SAA. Only two reports of successful laparoscopically resected SAA
      have appeared in the surgical literature. METHODS/RESULTS: The successful
      laparoscopic resection of a large expanding SAA was accomplished using a
      modification of currently described techniques. CONCLUSIONS: The semilateral
      decubitus position affords excellent access to the lesser sac, allowing excision
      of SAA with good visualization of the splenic artery and splenic hilar vessels
      should splenic hypoperfusion demand splenic resection. Excision of SAA is
      preferred to ligation except when dense adhesions or intrapancreatic arterial
      course preclude safe dissection. Pseudoaneurysms from trauma or pancreatitis are
      likely best treated with intraarterial embolization but significant complications
      should be expected in this high-risk subset of patients.

PMID- 11984679
TI  - Scientific data from clinical trials: investigators' responsibilities and rights.

PMID- 11984680
TI  - Laparoscopic treatment of a gastric outlet obstruction caused by a gallstone
      (Bouveret's syndrome).
AB  - Duodenal impaction of a gallstone after its migration through a
      cholecystoduodenal fistula is an uncommon cause of gallstone ileus described as
      Bouveret's syndrome. Surgical treatment is recommended, but the morbidity and
      mortality rates are nearly 60% and 30%, respectively. To reduce these rates using
      improved endoluminal surgery, a laparoscopically assisted intraluminal gastric
      surgery could be considered. A 74 year-old woman was admitted with typical
      Bouveret's syndrome. An intraluminal gastric laparoscopy was performed. The large
      stone impacted in the first duodenum was removed through the pylorus and pulled
      into the stomach. After its mechanical fragmentation, the stone was extracted
      with a sterile retriever bag through the main trocar. In the case of Bouveret's
      syndrome, treatment of the duodenal obstruction is mandatory. Surgical treatment
      of the cholecystoduodenal fistula still is controversial. We never perform a one
      stage procedure, and we reserve a biliary operation for the patient who remains
      symptomatic. In this way, laparoscopically assisted intraluminal gastric surgery
      with transpyloric extraction of the stone can be a safe and interesting approach
      for this type of pathology.

PMID- 11984681
TI  - Early experiences of endoscopic procedures in general surgery assisted by a
      computer-enhanced surgical system.
AB  - We performed a variety of complete total endoscopic general surgical procedures,
      including colon resection, distal gastrectomy, and splenectomy, successfully with
      the assistance of the da Vinci computer-enhanced surgical system. The robotic
      system allowed us to manipulate the endoscopic instruments as effectively as
      during open surgery. It enhanced visualization of both the operative field and
      precision of the necessary techniques, as well as being less stressful for the
      endoscopic operating team. This technological innovation can therefore help
      surgeons overcome many of the difficulties associated with the endoscopic
      approach and thus has the potential to enable more precise, safer, and more
      minimally invasive surgery in the future.

PMID- 11984682
TI  - The effect of hepatic inflow occlusion on laparoscopic radiofrequency ablation
      using simulated tumors.
AB  - BACKGROUND: The purpose of this study was to determine the effect of hepatic
      inflow occlusion (the Pringle maneuver) on laparoscopic radiofrequency (RF)
      ablation. METHODS: Using a previously validated agarose tissue-mimic model, 1-cm
      simulated hepatic tumors (three per animal) were laparoscopically ablated in five
      pigs with normal perfusion and then in five pigs with hepatic artery and portal
      vein occlusion. Energy was applied until tissue temperature reached 100 degrees C
      (warm-up) and thereafter for eight min. Specimens were examined immediately after
      treatment. RESULTS: Vascular occlusion was successful in all cases per color-flow
      Doppler ultrasound. Pringle time was 11.4 +/- 1.6 min. Warm-up time (2.7 +/- 1.4
      vs 20.2 +/- 14.0 min) was significantly faster in the Pringle group. Ablation
      diameter (34.8 +/- 2.9 vs 24.7 +/- 3.1 mm), proportion of round/ovoid lesions
      (93% vs 20%), ablation symmetry (100% vs 40%), and margin distance (5.1 +/- 3.0
      vs 1.1 +/- 1.2 mm) were significantly better for the Pringle group than the No
      Pringle group, respectively. CONCLUSION: Using a Pringle maneuver during
      laparoscopic RF ablation significantly enhances ablation geometry and results in
      larger margins.

PMID- 11984683
TI  - Symptomatic improvement in gastroesophageal reflux disease (GERD) following
      laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: The purpose of this study was to determine the effect of laparoscopic
      Roux-en-Y gastric bypass (LRYGBP) on symptomatic control of gastroesophageal
      reflux disease (GERD). METHODS: Morbidly obese patients (n = 435) who underwent
      LRYGBP for morbid obesity were assessed for changes in GERD symptoms, quality of
      life, and patient satisfaction after surgery. RESULTS: A total of 238 patients
      (55%) had evidence of chronic GERD, and 152 patients (64%) voluntarily
      participated in the study. The mean body mass index (BMI) was 48 kg/m2. The mean
      excess weight loss was 68.8% at 12 months. There was a significant decrease in
      GERD-related symptoms, including heartburn (from 87% to 22%, p<0.001); water
      brash (from 18% to 7%, p<0.05); wheezing (from 40% to 5%, p<0.001) laryngitis
      (from 17% to 7%, p<0.05); and aspiration (from 14% to 2%, p<0.01) following
      LRYGBP. Postoperatively, the use of medication decreased significantly both for
      proton pump inhibitors (from 44% to 9%, p<0.001) and for the H2 blockers (from
      60% to 10%, p<0.01). SF-36 physical function scores and the mental component
      summary scores improved after the operation (87 vs 71; p<0.05 and 83 vs 66;
      p<0.05, respectively). Overall patient satisfaction was 97%. CONCLUSION: LRYGBP
      results in very good control of GERD in morbidly obese patients with follow-up as
      late as 3 years. Morbidly obese patients who require surgery for GERD may be
      better served by LRYGBP than fundoplication because of the additional benefit of
      significant weight loss.

PMID- 11984684
TI  - Results of laparoscopic vs open resections for colon cancer in patients with a
      minimum follow-up of 3 years.
AB  - BACKGROUND: Laparoscopic resection for colon cancer is still a controversial
      procedure, the major cause of concern being the lack of long-term results. The
      aims of this study was to compare long-term outcome in unselected patients
      undergoing either laparoscopic (LH) or open hemicolectomy (OH) for colonic
      cancer. METHODS: From March 1992 to August 1997, 197 elective patients were
      included in this prospective nonrandomized study. The patients were operated on
      by the same surgical team following the same type of surgical technique for both
      right and left hemicolectomy, excluding segmental resections; the only difference
      was the type of access, which was either laparoscopic or open. Each patient gave
      a written consent, and the allocation to each group (laparoscopic or open) was
      done on the basis of the patient's choice. The long-term outcomes of the two
      groups were compared. Follow-up for both groups ranged from 36 to 96 months
      (mean, 48.9). RESULTS: In all, 149 (74 LH, 75 OH) of 197 patients were studied,
      excluding palliative resections, conversions to open surgery, perioperative
      deaths, and deaths not related to cancer. Only two patients in the laparoscopic
      group were lost to follow-up. The local recurrence after LH was 1.3% vs 2.7%
      after OH (p = 0.105). Metachronous metastases rates were similar for the two
      groups (10.8% for LH and 10.7% for OH). Cumulative survival probability (CSP) in
      the LH group vs the OH group was 0.892 vs 0.867 (p = 0.513), respectively. CSP
      for Duke's stage B and C in the LH group vs the OH group was 0.910 vs 0.895 (p =
      0.506) and 0.800 vs 0.734 (p = 0.544) respectively. Sixty-four LH patients
      (86.5%) and 65 OH patients (86.7%) are disease-free. CONCLUSION: In our series of
      patients, no statistically significant difference was found between the two
      groups in terms of long-term survival rate.

PMID- 11984685
TI  - After 10 years and 1903 inguinal hernias, what is the outcome for the
      laparoscopic repair?
AB  - BACKGROUND: The procedure of choice for inguinal hernia repair has remained
      controversial for decades. The laparoscopic approach has now been utilized for
      more than 10 years, and a significant volume of patient outcomes is now available
      for review. METHODS: The hospital and office records of 1388 patients who
      underwent 1903 laparoscopic inguinal hernia repairs at Atlanta Medical Center
      during the past 10 years were retrospectively reviewed in order to determine
      demographics, recurrence rate, and complications. In addition, 123 hernia repairs
      were prospectively studied in 71 patients during this time period in order to
      accurately evaluate postoperative pain and return to activity. RESULTS: Two
      hundred fifty-five (13.4%) hernias were recurrent and 1648 (86.6%) were primary.
      Five hundred and fifteen (37.1%) hernias were bilateral. The total
      extraperitoneal approach was utilized for 1561 (82.0%) of the 1903 repairs. The
      average operative time was 75.4 (14-193) minutes. Estimated blood loss was 22.0
      (0-250) ml. Seventeen patients (1.2%) were converted to an open form of hernia
      repair. Minor complications occurred in 83 (6.0%) patients and major
      complications occurred in 18 (1.3%) patients. CONCLUSIONS: The laparoscopic
      approach is a safe form of inguinal hernia repair that offers the patient a
      shorter and less painful recovery with an extremely low recurrence rate.

PMID- 11984687
TI  - Science and industry: can this relationship be controlled?

PMID- 11984689
TI  - Laparoscopic vs open approach for Nissen fundoplication. A comparative study.
AB  - BACKGROUND: Several studies, most of them nonrandomized, have shown similar
      functional results for both laparoscopic and open Nissen fundoplication, the
      operation of choice for the treatment of gastroesophageal reflux disease (GERD).
      METHODS: A total of 106 patients with documented GERD were randomized to receive
      either a laparoscopic or an open Nissen fundoplication. Preoperative and
      postoperative investigations included clinical assessment, esophagogram, upper
      gastrointestinal endoscopy, esophageal manometry, and 24-h ambulatory pHmetry.
      RESULTS: Both approaches were successful in controlling reflux. There was an
      overall improvement in esophageal peristalsis and an increase in lower esophageal
      sphincter (LES) pressure in both groups. Open Nissen fundoplication was
      associated with a significantly increased rate of wound (p <0.001) and
      respiratory (p <0.05) complications. Hospitalization was also longer after the
      open technique (p <0.001). At 3-month follow-up, although the rate of
      postoperative dysphagia was similar for the two approaches, the open approach was
      associated with a significantly higher incidence of postprandial epigastric
      fullness (p <0.05) and bloating syndrome (p <0.01). CONCLUSIONS: The open and
      laparoscopic approaches for the Nissen fundoplication are equally effective in
      controlling GERD. The open approach is associated with a significantly higher
      rate of wound and respiratory complications and, at early stages, an increased
      rate of postprandial epigastric fullness and abdominal bloating. The dysphagia
      rate is similar with both methods.

PMID- 11984690
TI  - Management of common bile duct stones: selective endoscopic retrograde
      cholangiography and endoscopic sphincterotomy: short- and long-term results.
AB  - BACKGROUND: Common bile duct stones are still a frequent problem. Although new
      diagnostic and therapeutic techniques are continually being development, they
      remain poorly defined. Therefore, we decided to evaluate our standard method of
      diagnosing and treating common bile duct stones. The aim of the study was to
      determine the short- and long-term results of this method. METHODS: Between 1985
      and 1995, 552 consecutive patients (200 men and 352 women; median age, 69 years)
      underwent endoscopic retrograde cholangiography (ERC) because of suspected common
      bile duct stones. If stones were detected, they were treated endoscopically, if
      possible. The results and complications of this policy were recorded. Patients
      were followed 1-13 years after undergoing ERC and endoscopic sphincterotomy (ES).
      Long-term results and complications during this period were also recorded.
      RESULTS: ERC was attempted in 552 patients and succeeded in 510 patients (92%):
      ES was attempted in 315 patients and failed in five (98%). Duct clearance was
      done in 271 patients; in 26 of these patients, symptoms disappeared
      spontaneously. Ten patients underwent common bile duct exploration. Complications
      occurred in 46 patients (8.3%). Mortality was 0.4%, hemorrhage occurred in 3.6%,
      pancreatitis in 1.4%, sepsis and cholangitis also in 1.4%, and the lithotripter
      basket became impacted in four patients (0.8%), necessitating to common bile duct
      exploration. During follow-up, 45 patients (8%) returned, 35 with recurrent
      stones, five with cholangitis, two with stenosis of the papilla of Vater, and one
      with biliary pancreatitis. In 35 cases, complications were treated
      endoscopically, common bile duct exploration was performed in five cases, and
      symptoms disappeared spontaneously in five cases. CONCLUSIONS: ERC is a safe and
      reliable way of diagnosing common bile duct stones, and ES is a very efficient
      way of treating them. Morbidity and mortality are low, and the long-term results
      are very good.

PMID- 11984691
TI  - Quantitative evaluation of three advanced laparoscopic viewing technologies: a
      stereo endoscope, an image projection display, and a TFT display.
AB  - BACKGROUND: Compared to open surgery, minimally invasive surgery (MIS) relies
      heavily on advanced technology, such as endoscopic viewing systems and innovative
      instruments. The aim of the study was to objectively compare three
      technologically advanced laparoscopic viewing systems with the standard viewing
      system currently used in most Dutch hospitals. METHODS: We evaluated the
      following advanced laparoscopic viewing systems: a Thin Film Transistor (TFT)
      display, a stereo endoscope, and an image projection display. The standard
      viewing system was comprised of a monocular endoscope and a high-resolution
      monitor. Task completion time served as the measure of performance. Eight
      surgeons with laparoscopic experience participated in the experiment. RESULTS:
      The average task time was significantly greater (p <0.05) with the stereo viewing
      system than with the standard viewing system. The average task times with the TFT
      display and the image projection display did not differ significantly from the
      standard viewing system. CONCLUSION: Although the stereo viewing system promises
      improved depth perception and the TFT and image projection displays are supposed
      to improve hand-eye coordination, none of these systems provided better task
      performance than the standard viewing system in this pelvi-trainer experiment.

PMID- 11984693
TI  - Toward understanding the functions of the two highly related Sox5 and Sox6 genes.

PMID- 11984694
TI  - The current strategy on the prevention and treatment of osteoporosis in Taiwan.

PMID- 11984695
TI  - C-type natriuretic peptide/guanylate cyclase B system in ATDC5 cells, a
      chondrogenic cell line.
AB  - Natriuretic peptides constitute a family of three structurally related peptides:
      atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type
      natriuretic peptide (CNP). Particulate guanylate cyclases, GC-A, and GC-B, are
      the receptors for these peptides to mediate their action. ANP and BNP possess
      high affinities for GC-A, and CNP is the preferred ligand for GC-B. In this
      article, we report our study of the expression and possible role(s) of
      natriuretic peptides in ATDC5 cells, which represent a chondrogenic cell line.
      ATDC5 cells produced cyclic guanosine monophosphate (cGMP) in response to
      natriuretic peptides. CNP was far more potent than ANP in terms of cGMP
      production. The messages for GC-A and GC-B were demonstrated by means of Northern
      blot analysis, and the presence of CNP was shown by Southern blotting coupled
      with reverse transcription-polymerase chain reaction (RT-PCR). These results
      suggest that the CNP/GC-B system is preferentially expressed in ATDC5 cells. GC-B
      mRNA expression was higher at 14 days after confluency than that at confluency.
      CNP or 8-bromo cGMP reduced [3H] thymidine uptake and slightly increased the
      message for collagen type X, which is a marker of hypertrophic chondrocytes.
      These data suggest that the CNP/GC-B system is likely to be an
      autocrine/paracrine regulator of ATDC5 cells, thus affecting both their growth
      and differentiation.

PMID- 11984696
TI  - Inhibition of growth plate angiogenesis and endochondral ossification with
      diminished expression of MMP-13 in hypertrophic chondrocytes in FGF-2-treated
      rats.
AB  - Fibroblast growth factors (FGFs)/fibroblast growth factor receptor-3 signaling
      interferes with endochondral bone growth. However, the exact mechanisms by which
      FGFs inhibit endochondral ossification remain to be elucidated. In the present
      study, we utilized immunohistochemical techniques to clarify the effects of FGF-2
      on the proximal tibial growth plate cartilage, when injected systemically into
      growing rats. In the FGF-2-treated rats, the growth plate was obviously thickened
      and, in the lowermost part, the hypertrophic chondrocytes were flattened, with an
      irregular arrangement. The connection of the cartilage columns and trabecular
      bone was disrupted. FGF-2 treatment stimulated the proliferation of chondrocytes
      and permitted their differentiation, but inhibited vascular invasion and
      resorption of the cartilage matrix. Expression of matrix metalloproteinase-13
      (MMP-13) was detected in the chondrocytes in the last row of the hypertrophic
      zone of the growth plate in control animals. The immunoreactivity of MMP-13 was
      diminished in the regions where endochondral ossification was disturbed in the
      FGF-2-treated rats. Because MMP-13 has potent proteolytic activity on cartilage
      components, the FGF-2 signal may inhibit angiogenesis and endochondral
      ossification of the growth plate by the suppression of MMP-13 expression in
      hypertrophic chondrocytes.

PMID- 11984697
TI  - Anabolic effect of phosphogenistein and phosphodaidzein on bone components in rat
      femoral-metaphyseal tissues in vitro.
AB  - The effect of phosphogenistein and phosphodaidzein, which are phosphorylated for
      the hydroxyl group (OH) at the 7-position of genistein and daidzein, on bone
      components was investigated. Femoral-metaphyseal tissues obtained from male rats
      (4 weeks old) were cultured for 24-72 h in Dulbecco's modified Eagle's medium
      (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The
      presence of phosphogenistein (10(-5) M) caused a significant increase in calcium
      content, alkaline phosphatase activity, and deoxyribonucleic acid (DNA) content
      in bone tissues cultured for 24 h. Phosphodaidzein (10(-5) M) significantly
      elevated bone calcium and DNA content. These effects were completely prevented by
      the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis. When
      femoral-metaphyseal tissues were cultured for 48 h in the presence of parathyroid
      hormone (1-34) (PTH; 10(-8) M) or prostaglandin E2 (PGE2; 10(-6) M), bone calcium
      content was significantly decreased. This decrease was significantly blocked by
      the presence of phosphogenistein (10(-6) and 10(-5) M) or phosphodaidzein (10(-6)
      and 10(-5) M). The presence of PTH (10(-8) M) or PGE2 (10(-6) M) caused a
      significant increase in glucose consumption and lactic acid production by bone
      tissues. These increases were significantly inhibited by the presence of
      phosphogenistein (10(-5) M) or phosphodaidzein (10(-5) M), indicating their
      inhibitory effect on bone resorption. The present study has demonstrated that
      both phosphogenistein and phosphodaidzein have an anabolic effect on bone
      metabolism in rat femoral-metaphyseal tissues in vitro.

PMID- 11984698
TI  - Pedigree-based quantitative genetic analysis of interindividual variation in
      circulating levels of IGFBP-3.
AB  - Circulating levels of insulin-like growth factor binding protein-3 (IGFBP-3) vary
      greatly between normal individuals, but until now little attention has been given
      to the study of the genetic factors involved in IGFBP-3 variability in healthy
      populations. The present study investigated the extent and pattern of the
      possible genetic influences on plasma levels of IGFBP-3 in 91 nuclear and more
      complex families, totaling 396 individuals (201 males and 195 females) of
      Caucasian ethnic origin. The variance decomposition analysis, was performed using
      the FISHER statistical package. In the second stage of the analysis, we used
      complex segregation analysis as implemented in the statistical package MAN.
      Significant negative correlation was revealed between age and plasma levels of
      IGFBP-3 in both sexes ( r=-0.49; r=-0.23; P<0.001). Multivariate analysis
      identified age, body weight, and height as significant covariates in men, but for
      women only age had a considerable effect. It has been demonstrated that about
      57.7% of IGBP-3 variation adjusted for significant confounding factors was
      attributable to genetic factors. The results of bivariate variance decomposition
      analysis showed no significant genetic and phenotypic correlation between the
      mineral density of hand bones and IGFBP-3. Segregation analysis revealed the
      existence of a potential major gene effect that was able to explain some 27.5% of
      IGFBP-3 variation. Multifactorial effects, likely, unknown minor genes,
      contributed an additional 30% to IGFBP-3 variation. The segregation analysis also
      provided evidence of significant genotype X sex interaction in the determination
      of plasma levels of IGFBP-3.

PMID- 11984699
TI  - Association of gene polymorphisms and bone density in Japanese girls.
AB  - Although some studies have reported a relationship between several candidate
      polymorphic genes and bone mineral density (BMD), little is known concerning the
      genetic factors influencing BMD in children. This study examined this
      relationship in healthy Japanese girls (n=125; age, 13.4 +/- 0.89 years; range,
      12-15 years). We investigated allelic variants of the vitamin D receptor (VDR)
      gene, the estrogen receptor (ER) gene, the parathyroid hormone (PTH) gene, the Ca
      sensing receptor (CaSR) gene, and the beta3-adrenergic receptor (beta3-AR) gene.
      The genotype of the VDR gene (Fok I) correlated with lumbar spine, and femoral
      neck BMD. The PTH polymorphisms (BstB I, Dra II) were also associated with lumbar
      spine BMD. No relationship was found between genotypes of the ER gene, CaSR gene,
      or beta3-AR gene and BMD. The age, height, weight, and body mass index did not
      differ significantly among girls with different VDR and PTH genotypes. These
      results suggest that the Fok I polymorphism of the VDR gene and the Dra II
      polymorphism of the PTH gene are risk factors for low bone density in Japanese
      girls.

PMID- 11984700
TI  - Alendronate and pharmacological doses of 1alpha OHD3 therapy in a patient with
      McCune-Albright syndrome and accompanying hypophosphatemia.

PMID- 11984701
TI  - Increased bone resorption with decreased activity and increased recruitment of
      osteoblasts in osteogenesis imperfecta type I.
AB  - An iliac bone biopsy from an adult male, 58 years of age, with osteogenesis
      imperfecta type I was studied by bone histomorphometry after double-fluorescence
      labeling with tetracycline. Low bone mineral density (BMD) of the radius,
      measured by dual-energy X-ray absorptiometry (DXA) was associated with high
      levels of urinary deoxypyridinoline and serum bone-specific alkaline phosphatase
      and osteocalcin. At the tissue level, low cancellous bone volume (BV/TV) was
      associated with increased eroded surface (ES/BS) and a relatively increased
      osteoclast number (N.Oc/BS). Osteoid thickness (O.Th) was also decreased as a
      result of decreased bone matrix synthesis, in terms of decreased osteoblastic
      activity. However, osteoid surface (OS/BS) and osteoblast surface (ObS/BS), in
      terms of the number of osteoblasts, were increased. We conclude that the patient
      showed cancellous osteopenia, which was likely due to increased bone resorption
      with decreased activity and increased recruitment of osteoblasts.

PMID- 11984702
TI  - Meeting report of the 72nd Japanese Gastric Cancer Congress.

PMID- 11984703
TI  - Screening for gastric cancer in Japan.
AB  - In Japan, mass screening for gastric cancer with photofluorography was initiated
      in 1960. At present, over 6 million people are screened annually. The sensitivity
      and specificity of photofluorography are 70%-90% and 80%-90%, respectively. The 5
      year survival rate is 15%-30% better in screen-detected cancers than in symptom
      diagnosed cases. Although no randomized controlled trials have been reported,
      cohort and case-control studies generally showed a decreased risk of mortality
      from gastric cancer in the screened subjects. The summary odds ratio (95%
      confidence interval) of three case-control studies for ever screened versus never
      screened subjects was 0.39 (0.29-0.52) for men and 0.50 (0.34-0.72) for women.
      Substantial evidence indicates that the Japanese screening program with
      photofluorography is effective in reducing the mortality from gastric cancer. The
      measurement of serum pepsinogens has recently drawn attention as an alternative
      to photofluorography, given its lower cost and simplicity. Some studies have
      suggested a comparable accuracy for the two methods. However, these
      investigations may have overestimated the relative sensitivity of serum
      pepsinogen testing compared with photofluorography, because serum pepsinogen
      testing was conducted as prevalent screening, while photofluorography was done as
      incident screening. Furthermore, no studies have directly examined whether the
      screening with serum pepsinogens reduced gastric cancer mortality. Therefore, at
      present, evidence is insufficient to determine the benefit of this program.

PMID- 11984704
TI  - Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients
      with bone metastasis.
AB  - BACKGROUND: Patients with bone metastasis of gastric cancer occasionally
      experience disseminated intravascular coagulation (DIC), with a very poor
      prognosis.METHODS: We treated 18 gastric cancer patients with bone metastasis
      with sequential methotrexate and 5-fluorouracil (sequential MTX/5-FU therapy).
      The treatment schedule comprised weekly administration of methotrexate (MTX; 100
      mg/m(2), i.v. bolus) followed by 5-fluorouracil (5-FU; 600 mg/m(2), i.v. bolus)
      after an interval of 3 h. Calcium leucovorin (10 mg/m(2), p.o. or i.v.) was
      administered six times, every 6 h starting 24 h after the administration of
      MTX.RESULTS: In 11 patients with measurable metastatic lesions, the response rate
      was 64% (7/11). Nine patients (50%) had DIC before the initiation of
      chemotherapy, and 8 of them (89%) recovered from it. Two of these 9 patients
      (22%) survived for more than 1 year. The median survival times for all patients
      and for the 9 with DIC were 186 and 113 days, respectively. Grade 4 leukopenia
      was observed in 3 patients (17%). No treatment-related deaths
      occurred.CONCLUSION: Sequential MTX/5-FU therapy may have palliative potential
      and may be a feasible treatment for gastric cancer patients with bone metastasis
      with or without DIC.

PMID- 11984705
TI  - Influence of perioperative blood transfusion on the prognosis of patients with
      gastric cancer receiving anticancer chemotherapy.
AB  - BACKGROUND: The deleterious effect of blood transfusions on survival has been
      reported in patients with cancers of various organs. However, it remains unclear
      whether there is any adverse effect of blood transfusion when the patients are
      administered anticancer drugs after surgery for gastric cancers.METHODS: Data
      from patients with gastric resection for advanced gastric cancer were
      retrospectively analyzed to determine the influence of perioperative blood
      transfusion on the survival rate. All patients were administered anticancer drugs
      (mitomycin C [MMC] and tegafur-uracil [UFT]). Sixty-nine (33%) of 208 patients
      received blood transfusion perioperatively, while 139 patients (67%) did not
      receive transfusion. Multivariate analysis of clinicopathologic prognostic
      factors, including blood transfusion, was performed. Lymphocyte subsets were
      measured to investigate the immunosuppressive effect of blood
      transfusion.RESULTS: The 5-year survival rate was 48.8% in the 69 transfused
      patients and 66.9% in the 139 non-transfused patients ( P < 0.01). Cox's multiple
      regression analysis showed that, when patients received anticancer drugs,
      perioperative blood transfusion was not a significant factor affecting survival
      after the gastric cancer surgery. However, the CD4/CD8 ratio at 3 months after
      the surgery was significantly lower in the transfused group than in the non
      transfused group.CONCLUSION: Blood transfusion did not affect the survival of
      operated patients who received postoperative adjuvant chemotherapy. However, the
      finding that the ratio of CD4/CD8 after surgery was significantly higher in the
      non-transfused group than in the transfused group supports the notion that
      transfusion causes broad-spectrum immunosuppression.

PMID- 11984706
TI  - Prediction of recurrence after curative resection of gastric carcinoma invading
      the muscularis propria: a multivariate analysis.
AB  - BACKGROUND: In Japan, the incidence of gastric cancer invading the muscularis
      propria is about 10% of all patients with gastric cancer undergoing surgical
      resection. Although many prognostic factors for early gastric cancer and advanced
      gastric cancer have been identified, there are few reports concerning prognostic
      factors for gastric cancer invading the muscularis propria, and the
      characteristics of recurrence are not well understood.METHODS: We retrospectively
      analyzed data on 167 patients with gastric cancer that had invaded the muscularis
      propria. All patients had undergone curative resection.RESULTS: Recurrences were
      evident in 37 patients (22.2%). Based on our univariate analysis, the recurrence
      was associated with lymph node metastases. Multivariate analysis showed that
      independent risk factors for recurrence were lymph node metastases and location
      of tumor in the upper or lower one-third of the stomach. With respect to the
      pattern of recurrence, 17 (46.0%) were secondary to hematogenous recurrence, 8
      (21.6%) to peritoneal dissemination, and 6 (16.2%) to a local recurrence in the
      remnant stomach and in regional lymph nodes. Most deaths occurred during the
      second year after surgery, and approximately two-thirds of all patients (64.8%)
      died within 3 years after surgery.CONCLUSION: In patients with the risk factors
      of lymph node metastases and tumor in the upper or lower one-third of the
      stomach, lymph node dissection and postoperative adjuvant therapy are vital to
      try to prevent recurrences, especially during the first 2 years after surgery.

PMID- 11984707
TI  - Papillary adenocarcinoma of the stomach.
AB  - BACKGROUND: Papillary gastric carcinoma (PGC) is a rare histologic entity among
      gastric adenocarcinomas. The aim of this study was to clarify the
      clinicopathologic characteristics of PGC, including the survival rate, recurrence
      pattern, and factors influencing the prognosis of patients with PGC.METHODS: The
      clinicopathologic findings of 65 patients with PGC and 566 patients with non
      papillary gastric carcinoma (NGC) were examined and compared. The tumor was
      classified as PGC when more than 50% of the tumor area contained papillary
      structures. Survival rates were calculated using the Kaplan-Meier method and were
      assessed by the generalized Wilcoxon test. Prognostic factors were evaluated by
      univariate analysis, using the chi(2) test and Student's t-test, and confirmed by
      multivariate analysis, using the Cox proportional hazards model.RESULTS: PGC was
      characteristically found in patients over 65 years of age (68%), was located in
      the upper one-third of the stomach (37%), was of grossly localized type (85%),
      was negative for serosal invasion (86%), and was associated with liver metastasis
      (14%). The overall 5-year survival rate for patients with PGC was significantly
      lower than the rate for those with NGC (63% vs 76%) ( P < 0.05). Although the 5
      year survival rate for each stage of PGC and NGC did not differ significantly,
      the death of PGC patients was more frequently associated with liver metastasis
      (62%) than with peritoneal dissemination (5%). Independent prognostic factors of
      PGC were liver metastasis, serosal invasion, and lymph node
      metastasis.CONCLUSION: These results suggest that PGC is characterized by
      advanced patient age, proximal tumor location, grossly localized type, negative
      serosal invasion, and frequent liver metastasis. A poor prognosis for patients
      with PGC is associated with the presence or recurrence of liver metastasis.

PMID- 11984708
TI  - A model chemosensitivity test examining apoptosis in small specimens of gastric
      cancer.
AB  - BACKGROUND: Because chemosensitivity tests usually require a large amount of
      tissue, they are not used routinely in patients with unresectable gastric cancer.
      The aim of this study was to investigate whether apoptosis can be used as a
      sensitivity assay for chemosensitivity in small gastric cancer specimens.METHODS:
      Apoptosis, detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick labeling (TUNEL), was investigated in small specimens of the MKN-1, MKN-45,
      and TMK-1 human gastric cancer cell lines as a marker of chemosensitivity
      following exposure to antineoplastic agents.RESULTS: Doxorubicin (DXR), SN-38
      (active metabolite of irinotecan), and paclitaxel (Taxol) induced DNA
      fragmentation in MKN-45 and TMK-1 cells, but not in MKN-1. In contrast, neither 5
      fluorouracil (5-FU) nor cisplatin (CDDP) induced DNA fragmentation in any of the
      three cell lines. Small pieces cut from tumors implanted in nude mice were
      exposed to the antineoplastic agents in culture medium for 24 h, and the
      percentage of TUNEL-positive cancer cells (TUNEL positivity) was examined. TUNEL
      positivity in all three cancers increased after exposure to DXR, SN-38, and
      Taxol, but not after exposure to CDDP or 5-FU. MKN-45 showed the highest TUNEL
      positivity with SN-38 and Taxol, and TMK-1 TUNEL positivity was highest with DXR.
      MKN-45 and TMK-1 were the most sensitive to these three antineoplastic agents in
      vitro, while MKN-1, with the lowest TUNEL positivity, was the least sensitive to
      these three antineoplastic agents. TUNEL positivity after exposure to Taxol
      correlated with the antitumor effects of this compound in an animal
      model.CONCLUSION: These results suggest that, in small gastric cancer specimens
      where apoptosis is implicated, TUNEL positivity may be applicable to a
      chemosensitivity test.

PMID- 11984709
TI  - Histological differences in the invasion of advanced esophageal and gastric
      carcinoma beyond the esophago-gastric junction.
AB  - BACKGROUND: The esophago-gastric junction (EGJ) has several unique anatomical and
      histological features. We investigated the histological differences between
      esophageal squamous cell carcinoma with invasion of the gastric wall (esophageal
      group of patients) and gastric carcinoma with invasion of the esophageal wall
      (gastric group of patients).METHODS: Thirty-six patients in the esophageal group
      and 83 patients in the gastric group were histologically examined in regard to
      the mode of invasion. The pattern of tumor invasion beyond the EGJ was classified
      as continuous or discontinuous.RESULTS: The discontinuous pattern was more
      frequently seen in the esophageal group than in the gastric group. In the gastric
      group, however, the distance invaded beyond the EGJ was significantly greater in
      tumors with the discontinuous pattern than in those with the continuous pattern (
      P < 0.01). Gastric mucosal invasion at the EGJ was not seen in 36% of the
      esophageal group, whereas tumor infiltration into the esophageal mucosal layer at
      the tip beyond the EGJ was found in 60% of the gastric group. The incidence of
      invasion deeper than the muscularis propria in the gastric and esophageal groups
      was 18% and 58%, respectively ( P < 0.0001).CONCLUSION: The histological
      characteristics of esophageal or gastric carcinoma beyond the EGJ should be taken
      into consideration in diagnosis and surgical procedures.

PMID- 11984711
TI  - A wider audience for Japanese research through use of the Web.

PMID- 11984710
TI  - Laparoscopic D2 lymph node dissection for advanced gastric cancer located in the
      middle or lower third portion of the stomach.
AB  - The standard lymph node dissection for advanced gastric cancer is a D2
      dissection, performed in accordance with the new Japanese classification of
      gastric carcinoma (13th edition). Although laparoscopic D2 dissections according
      to the General rules for gastric cancer study (12th edition) have been reported,
      no studies have reported laparoscopic D2 dissections according to the revised
      classification for advanced gastric cancers located in the middle or lower
      portions of the stomach. The lack of such studies is due to the perceived
      technical difficulty of the procedure. However, we successfully performed this
      novel procedure in five patients with advanced gastric cancer located in the
      middle or lower portions of the stomach. In fact, this surgical procedure is
      technically feasible and safe.

PMID- 11984712
TI  - Clinical relevance of telomerase activity in primary gastric lymphoma.
AB  - BACKGROUND: To distinguish between low-grade lymphoma and reactive lymphoid
      infiltrate can be demanding for pathologists. Demonstration of B-cell
      monoclonality by polymerase chain reaction (PCR) analysis of immunoglobulin heavy
      chain is useful as referential data. Telomerase activity, which is frequently
      detected in malignant tumors while being undetectable in normal tissues, may also
      have a supportive role in the diagnostic procedure, but has not been investigated
      in specimens of primary gastric lymphoma. METHODS: Telomerase activity was
      qualitatively and quantitatively evaluated, using fluorescence-based telomeric
      amplification assay protocol (TRAP) analysis, in 16 malignant lymphoma and
      related specimens, including 7 specimens of low-grade mucosa-associated lymphoid
      tissue (MALT) lymphoma, among which specimens before and after Helicobacter
      pylori eradication were evaluated from five patients. RESULTS: Telomerase
      activity was detected more frequently (6 of 7 specimens) at higher levels in high
      grade lymphoma compared with low-grade MALT lymphoma. It was detected in 3 of 7
      specimens of low-grade MALT lymphoma, but was undetectable either at the stage of
      Helicobacter pylori-induced gastritis or after H. pylori eradication therapy.
      CONCLUSION: Telomerase activity evaluated by fluorescence-based TRAP analysis was
      detectable late in the process of evolution of MALT lymphoma and was undetectable
      early in the process of regression. It was frequently and overtly elevated in
      high-grade lymphoma. Telomerase activity may have a role in confirming the
      histologic diagnosis of primary gastric lymphoma.

PMID- 11984713
TI  - Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer.
AB  - BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is an important matrix-degrading
      enzyme that has a large role in the invasion and metastasis of cancer. To
      discover the mechanism of the formation of peritoneal dissemination in gastric
      cancer, we studied the mRNA and protein expression of MMP-7 in primary gastric
      cancers and peritoneal dissemination.METHODS: MMP-7 expression in primary gastric
      cancers (136 patients) was studied by immunohistochemistry and reverse
      transcription-polymerase chain reaction (RT-PCR), and the results were compared
      with chinicopathological parameters.RESULTS: MMP-7 mRNA was expressed in 28 (53%)
      of 53 primary gastric cancers, but not in normal gastric mucosa, fibroblasts, or
      mesothelial cells. An immunohistochemical method demonstrated that MMP-7
      immunoreactivity was found on the cell membrane and cytoplasm of cancer cells.
      Among 136 primary tumors, 70 (53%) tumors overexpressed MMP-7, and MMP-7 tissue
      status had significant positive correlation with serosal involvement, lymph node
      metastasis, poor differentiation of cancer, and peritoneal dissemination.
      Patients with MMP-7-positive tumor had significantly poorer survival and more
      frequently died of peritoneal recurrence than did those with MMP-7-negative
      tumors. All 6 examined peritoneal disseminations expressed MMP-7 mRNA, and 13 of
      14 peritoneal disseminations showed immunoreactivity to anti-human MMP-7
      monoclonal antibody. Logistic regression analysis showed that MMP-7
      immunohistological status was an independent risk factor for peritoneal
      dissemination, and patients with MMP-7 mRNA-positive tumors had a 9.9-fold higher
      relative risk for peritoneal metastasis.CONCLUSION: These results strongly
      suggest that MMP-7 may have a large role in the formation of peritoneal
      dissemination in gastric cancer, and that clonal selection of cancer cells with
      MMP-7 overexpression may occur during the invasion of intraperitoneal free cancer
      cells from the peritoneal surface into the subperitoneal tissue. MMP-7 tissue
      status in the primary tumor may be a good indicator of peritoneal dissemination.

PMID- 11984714
TI  - Prognostic factors in stage IV gastric cancer: univariate and multivariate
      analyses.
AB  - BACKGROUND: The prognosis of stage IV gastric cancer is poor with the 5-year
      survival rate still being about 10%.METHODS: We classified 130 patients with
      stage IV gastric cancer into four groups: peritoneal metastasis, liver
      metastasis, lymph node metastasis, and multiple factor groups, according to the
      factors that determined stage IV in each patient and compared survival in the
      four groups. We also performed univariate and multivariate analyses of various
      prognostic clinicopathological factors. The 5-year survival rate in the patients
      with stage IV gastric cancer was 7.4%.RESULTS: No significant differences were
      observed in survival among the four groups. Univariate analysis showed
      significant differences in survival among the categories of lymphatic invasion (
      P = 0.0045), venous invasion ( P = 0.0024), peritoneal metastasis ( P = 0.0019),
      postoperative chemotherapy ( P = 0.0385), curability ( P = 0.0001), and lymph
      node dissection ( P = 0.0001). In the curability B group, survival was prolonged
      in the postoperative chemotherapy group. Multivariate analysis revealed the
      highest relative hazard (RH) for lymph node dissection (RH, 2.261), followed, in
      descending order, by curability (RH, 1.905), peritoneal metastasis (RH, 1.896),
      lymphatic invasion (RH, 1.736), and venous invasion (RH, 1.481).CONCLUSION: As
      prognostic factors in stage IV gastric cancer, the tumor factors of peritoneal
      metastasis and vessel invasion, and the treatment factors of curability and lymph
      node dissection may be important, and active treatment appears to improve
      survival.

PMID- 11984715
TI  - A micrometric classification of intramucosal carcinomas of the stomach.
AB  - BACKGROUND: The aim of this study was to assess whether the results of
      micrometric measurements could be correlated with the macroscopic-endoscopic
      classification of intramucosal carcinomas of the stomach.METHODS: The thickness
      of 86 consecutive intramucosal gastric carcinomas (IMGCs) was micrometrically
      assessed. IMGCs having more than twice the thickness of the non-involved gastric
      mucosa (NIGM) were regarded as protruding (type I) and those having twice or less
      of the thickness of the NNGM, as non-protruding (type II). Non-protruding IMGCs
      were subclassified as elevated (thicker than NNGM, or type IIa), flat (the same
      thickness as NNGM, or type IIb), and depressed (thinner than NNGM, or type
      IIc).RESULTS: Only 9.3% ( n = 8) of the 86 IMGCs were protruding and 90.7% ( n =
      78) were non-protruding. Of the 78 non-protruding IMGCs, 46.2% ( n = 36) were
      elevated (type IIa), 38.5% ( n = 30) were flat (type IIb), and the remaining
      15.4% ( n = 12) were depressed (type IIc). A low correlation was found when the
      micrometric and a similar gross classification were compared. Protruding and
      elevated IMGCs were often histologically of intestinal type (60.3%), whereas flat
      and depressed IMGCs were often of diffuse type (73.9%).CONCLUSION: Tumor
      differentiation may be related to the micrometric profile of the tumor. Non
      protruding IMGCs (type II) may expand laterally, without "becoming" protruding
      and without invading the submucosal layer.

PMID- 11984716
TI  - Relationship between interleukin-1-alpha concentration in tumors and cell growth
      in gastric cancer, determined using flow cytometry.
AB  - BACKGROUND: Interleukin-1-alpha (IL-1alpha) produced by tumor cells stimulates
      the proliferation or the growth of several cancer cell lines. The aim of this
      study was to clarify the relationship between growth activity evaluated by DNA
      analysis and the concentration of tumor-derived IL-1alpha in gastric cancers in
      clinical cases.METHODS: We measured the concentration of IL-1alpha in homogenized
      tumor samples obtained from 49 patients with gastric cancer, using an enzyme
      linked immunosorbent assay, and we analyzed the cellular DNA content of paraffin
      embedded tumor sections using flow cytometry.RESULTS: Both the IL-1alpha
      concentration and the percentage of S-phase fraction were significantly
      correlated with liver metastasis, histologic type, pattern of tumor infiltration,
      quantity of stroma, and venous invasion. A good correlation was found between IL
      1alpha concentration in tumors and the percentage of S-phase fraction ( R =
      0.604, P < 0.0001).CONCLUSION: IL-1alpha may be related to the stimulation of
      cell growth of gastric cancer in clinical cases.

PMID- 11984717
TI  - Micrometastasis in lymph nodes of mucosal gastric cancer.
AB  - BACKGROUND: Endoscopic mucosal resection is frequently used in the treatment of
      mucosal gastric cancer. Micrometastasis in the lymph nodes of mucosal gastric
      cancer remains unclear.METHODS: We examined 2526 lymph nodes from 84 patients
      with mucosal gastric cancer. Two consecutive sections were prepared, for
      simultaneous staining with hematoxylin and eosin and immunostaining with CAM 5.2
      monoclonal antibody against cytokeratin (CK), respectively. A clinicopathological
      comparison was made between patients with and without lymph node
      involvement.RESULTS: Lymph node involvement was detected in 45 of 2526 (1.8%)
      lymph nodes. The incidence of nodal involvement was significantly increased, from
      1.2% (1/84 patients) with hematoxylin and eosin staining, to 19% (16/84 patients)
      with CK immunostaining. Although no significant difference was found,
      micrometastasis to lymph nodes was more frequently detected in tumors larger than
      1.0 cm (15/72 patients, 21%) than in those less than or equal to 1.0 cm (1/12
      patients; 8%, P = 0.307). However, discrete CK-positive cancer cells or clusters
      of CK-positive cancer cells were detected only in tumors larger than 2
      cm.CONCLUSION: Because mucosal gastric cancer of more than 1.0 cm in superficial
      diameter may indicate a risk of micrometastasis to lymph nodes, endoscopic
      mucosal resection is not recommended for these patients.

PMID- 11984718
TI  - Decreasing complication rates with stapled esophagojejunostomy following a
      learning curve.
AB  - BACKGROUND: Recently, two reports of clinical trials on gastric cancer surgery
      have reported high mortality following extended lymph node dissection. In these
      reports, anastomotic leakage at the esophagojejunostomy was observed in
      approximately 10% of patients, with high mortality. These data highlight the
      importance of avoiding this complication. In this article, we report the use of a
      stapler to achieve a safe anastomosis, with low incidences of leakage and
      postoperative stenosis. METHODS: From January 1985 to December 1997, we performed
      1234 esophagojejunal anastomoses at the National Cancer Center Hospital. Records
      of the 1234 patients were reviewed to evaluate changes in anastomotic techniques
      and changes in the incidence of anastomotic leakage. In this series, 588 stapled
      anastomoses were carried out between 1992 and 1997. These were evaluated to
      calculate the incidence of leakage and stenosis, with special reference to the
      use of supplementary sutures around the stapled anastomosis. Statistical analysis
      was performed by the chi2 test. RESULTS: This series showed an overall increase
      in the use of staplers to form the esophagojejunal anastomosis, and a decrease in
      the incidence of leakage. In 1995, all anastomoses were stapled, with a leakage
      rate of less than 1.0%. In the last 6 years of the series (1992-1997), the
      leakage rate was 1.0% and the incidence of postoperative stenosis was 1.2%. The
      results were not improved by supplementary sutures around the stapled
      anastomosis. CONCLUSION: These data show that a stapled esophagojejunal
      anastomosis without supplementary sutures is a safe way to create a
      esophagojejunal anastomosis, with results superior to those with hand suturing.
      We believe the stapled anastomosis should become the "gold standard" for
      esophagojejunal anastomosis.

PMID- 11984719
TI  - Gastric cancer recognized by metastasis to the ureter.
AB  - Although ureteral obstruction is rarely noted in patients with gastric cancer at
      an advanced stage or at autopsy, the condition caused by authentic ureteral
      metastasis of gastric cancer is extremely rare. We experienced a case of gastric
      cancer in a 51-year-old woman who showed bilateral ureteral metastasis. The
      patient initially complained of right flank pain, caused by right ureteral
      obstruction, and was referred to our hospital, where she underwent a right
      nephroureterectomy, with suspicion of primary ureteral neoplasm.
      Histopathological examination of the resected specimen showed that metastatic
      growth of adenocarcinoma in the ureteral wall had caused the obstruction, and the
      subsequent extensive search for the primary lesion revealed asymptomatic gastric
      cancer. Soon after the nephroureterectomy, the patient developed left
      hydronephrosis, possibly caused by left ureteral metastasis, and a left
      percutaneous nephrostomy was performed. She then received chemotherapeutic
      reagents. However, she finally developed peritoneal carcinomatosis, and died of
      the disease about 1 year after the onset of the disease. In this report, we also
      review true ureteral metastasis from the stomach, and discuss the
      clinicopathologic features.

PMID- 11984720
TI  - Five-year survivor with liver metastasis from gastric cancer successfully treated
      with systemic chemotherapy.
AB  - We report a patient with liver metastasis from gastric cancer who has achieved a
      5-year survival after systemic chemotherapy. The patient was diagnosed with
      advanced gastric cancer and received a total gastrectomy in August 1991, followed
      by adjuvant chemotherapy. Liver and lymph node metastases were detected in April
      1994, and systemic chemotherapy with a combination of etoposide, doxorubicin, and
      cisplatin was initiated. Although the liver metastasis completely disappeared,
      lymph node metastasis at the falciform ligament of the liver and around the
      portal fissure remained after six courses of this therapy. A second type of
      chemotherapy, a combination of 5-fluorouracil and methotrexate, was then
      administered, 12 times, from December 1994 to May 1995, during which time no
      disease progression was observed. After surgery for the metastatic lymph nodes in
      August 1995, no progression was observed until December 1998, when a tumor
      thrombus was detected in the portal vein. Combination chemotherapy of irinotecan
      and cisplatin was initiated in January 1999. Although tumor regression was
      achieved after two courses of this, the disease continued to progress after five
      courses. In July 1999, a fourth type of chemotherapy, using 1 M tegafur-0.4 M
      gimestat-1 M otastat potassium (S-1), was initiated, and size reduction of the
      tumor thrombus was achieved; this therapy has continued to the time of submission
      of this report.

PMID- 11984721
TI  - Extensive liver metastasis of gastric cancer effectively treated by hepatic
      arterial infusion of 5-fluorouracil/cisplatin.
AB  - Most gastric cancer patients with jaundice caused by extensive liver metastasis
      show no tumor shrinkage response to systemic chemotherapy, while often showing
      severe adverse reactions. Their prognosis is very poor. We experienced two
      patients for whom hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) and
      cisplatin through an implantable port was effective for treating extensive liver
      metastasis. One patient had jaundice (serum bilirubin level before HAI therapy,
      12.4 mg/dl) caused by metachronous liver metastasis, and prior systemic
      chemotherapy with 5-FU and irinotecan had not been effective. The other patient
      had gastric cancer with synchronous liver metastasis and also exhibited jaundice
      (serum bilirubin level before HAI therapy, 11.8 mg/dl). Both patients were
      treated with HAI of cisplatin, 20 mg/m(2) for 30 min on day 1, and continuous
      intraarterial infusion of 5-FU, 300 mg/m(2), from day 1 to day 4 every week.
      Their metastatic liver tumors were significantly reduced in volume and the
      jaundice disappeared. They survived for 30 and 27 weeks, respectively. A
      pharmacokinetic study conducted during the period of partial remission revealed
      that the extraction ratios of 5-FU and cisplatin in the liver were 0.89 and
      0.024, respectively, suggesting a favorable first-pass effect of 5-FU. Although
      our findings here suggest that the successful local control of liver metastasis
      could improve the deteriorated condition and prolong the survival in some
      patients with far advanced cancer, it is essential to pay much attention to
      possible adverse effects during the treatment.

PMID- 11984722
TI  - Redefining surgery for gastric cancer: is "stage-appropriate surgery" an
      appropriate standard for Western surgeons?

PMID- 11984723
TI  - The challenge of early gastric cancer: the need to optimize microstaging and
      therapy.

PMID- 11984724
TI  - Time trends for small gastric cancer in Japan.
AB  - BACKGROUND: Gastric cancer rates in Japan have been declining since the 1970s.
      The rate of differentiated carcinomas has decreased and that of undifferentiated
      carcinomas has increased. However, little is known about the time trends of small
      gastric cancer. The aim of this study was to investigate the trends of small
      gastric cancer over time in Japan. METHODS: We reviewed cases of small gastric
      cancer (less than 20 mm in diameter) in two groups of patients who entered the
      age range of 55-to-67 years 14 years apart: patients in cohort 1 (n = 66) were
      born between 1899 and 1912, and those in cohort 2 (n = 66) were born between 1926
      and 1936. Between-group comparisons were made for macroscopic, microscopic, and
      histochemical findings. Mucin histochemical analysis was used to investigate
      gastric and nongastric phenotypes. Helicobacter pylori was also investigated by
      immunohistochemistry. RESULTS: There were significant decreases in the incidence
      of elevated carcinoma (20% in cohort 1 vs 6% in cohort 2; P < 0.05) and papillary
      adenocarcinoma (11% vs 2%; P < 0.05). The incidence of flat carcinomas was
      significantly increased (3% vs 15%; P < 0.05). The incidence of tumors surrounded
      by fundic gland mucosa increased (20% vs 29%), whereas that of tumors surrounded
      by intestinal metaplastic mucosa decreased (52% vs 41%). The rate of H. pylori
      infection in mucosa surrounding tumors was the same in both groups (35%). The
      incidence of tubular adenocarcinoma with gastric-type mucin was higher in cohort
      2 (64%) than in cohort 1 (51%). CONCLUSION: The rate of tubular adenocarcinomas
      containing gastric type mucin has increased over time. These tumors had a
      tendency to develop in the fundic gland mucosa and to show less intestinal
      metaplasia. The H. pylori infection rate was unrelated to this time trend. In
      advanced gastric cancer, the differentiated carcinoma rate has decreased;
      however, in small gastric cancer, the rate of tubular adenocarcinoma containing
      gastric type mucin has increased. This suggests that tubular adenocarcinoma with
      gastric type mucin changes into poorly differentiated adenocarcinoma as tumors
      grow to advanced stages.

PMID- 11984725
TI  - Significance of and problems in adopting response evaluation criteria in solid
      tumor RECIST for assessing anticancer effects of advanced gastric cancer.
AB  - BACKGROUND: The response evaluation criteria in solid tumor (RECIST) exclude the
      use of barium meal studies. This will deeply affect the Japanese criteria for
      evaluating the response in the primary lesion of gastric cancer.METHODS: Of 280
      patients with gastric cancer enrolled in a Japan Clinical Oncology Group (JCOG)
      phase III study, 255 had been assessed for response by the WHO and/or Japanese
      criteria. We selected these 255 patients as our subjects and reassessed their
      response outcomes by RECIST.RESULTS: Of the 255 patients, 32 (13%) had no
      evaluable lesion other than the primary site, and 171 (67%) had some measurable
      lesion defined by the WHO criteria. Because the lesions in 129 of these 171
      patients were 20 mm or more in size, only 51% of the 255 subjects were eligible
      for assessment of the target lesion by RECIST. In 162 of the 171 patients who had
      a lesion of 10 mm or more, response rates by the old and new criteria were nearly
      equal, in spite of the different methods of measurement. The response rate in the
      primary lesions assessed by the Japanese criteria was lowest among all the groups
      examined.CONCLUSION: The RECIST is simple and good for clinical practice.
      Nevertheless, the recommendation of 20 mm or more for target lesions, which may
      restrict the number of eligible patients, could be replaced by a size of 10 mm or
      more. Because the Japanese evaluation criteria are rigid and do not inflate the
      response rate, they can be used, as additional criteria for assessing the quality
      of response, when the RECIST is used.

PMID- 11984726
TI  - The role of growth patterns, according to Kodama's classification, and lymph node
      status, as important prognostic factors in early gastric cancer: analysis of 412
      cases.
AB  - BACKGROUND: During the 1970s, a special type of Gastric Cancer with excellent
      prognosis (early gastric cancer; EGC) was identified by the Japanese Research
      Society for Gastric Cancer. EGC has been defined as a tumor which invades the
      mucosa and/or submucosa, regardless of the lymph node status. Using this
      definition, we identified an initial phase of tumor development which could be
      treated both endoscopically and surgically.METHODS: We examined 412 EGC patients,
      recruited between 1976 and 1999, with an average follow-up of 9 years. All tumors
      were classified according to the macroscopic and microscopic criteria proposed by
      the Japanese Society of Gastroenterological Endoscopy (JSGE) and Lauren,
      respectively. The infiltrative growth pattern was evaluated according to Kodama's
      classification. Only tumor-related death was considered as an end-point of
      interest for the survival analysis.RESULTS: Submucosal tumors ( P = 0.008), Pen A
      (see definition below) type disease ( P = 0.0001), and lymph node-positive
      cancers ( P = 0.0002) were significant prognostic factors on univariate analysis.
      Moreover, bivariate analysis showed that the worst prognosis, in terms of
      survival, was for patients with nodal involvment, submucosal invasion, and node
      positive and Pen-A type cancer. The abbreviation Pen, penetrating, indicates a
      lesion with a diameter of less than 4 cm, which invades the submucosa diffusely.
      Pen A type EGC represents a subgroup of tumors which infiltrates the submucosa
      extensively, with nodular masses, causing the complete destruction of the
      muscularis mucosae.CONCLUSION: In our series, Pen A type was an important
      prognostic factor (hazard ratio; HR, 8.32; 95% confidence interval [CI], 3.49
      19.86. For this reason, we believe it is important to evaluate the infiltration
      into the wall in all patients with EGC, paying particular attention to the growth
      pattern of the neoplasm. Moreover, submucosal Pen A type tumors had a
      considerably worse prognosis and this finding was reinforced when lymph node
      metastases coexisted. We suggest, therefore, that surgical treatment with at
      least a D2 lymphadenectomy is performed in all these patients, as the lesions
      must be considered to be advanced, no longer being EGC.

PMID- 11984727
TI  - Effect of fat volume on postoperative complications and survival rate after D2
      dissection for gastric cancer.
AB  - BACKGROUND: D2 lymph node dissection in gastric cancer is controversial in
      Western countries because of the relatively high complication and mortality
      rates. The purpose of this study was to clarify the effects of fat volume on
      operation factors, postoperative complications, and survival in gastric cancer
      surgery.METHODS: We studied 293 consecutive patients who had undergone distal
      gastrectomy with D2 dissection for gastric cancer at our hospital between 1990
      and 1997. The patients were classified into three groups according to their body
      mass index (BMI; kg/m(2)). We analyzed differences in the operation time, the
      amount of blood loss, the postoperative complications and the survival rate among
      the three groups.RESULTS: Group A patients had a BMI of less than 20 ( n = 61),
      group B had a BMI of 20-25 ( n = 178), and group C had a BMI of more than 25 ( n
      = 54). There were significant differences in operation time (group A, 206 +/- 66
      min; group B, 226 +/- 61 min; group C, 252 +/- 61 min; P < 0.05), blood loss
      (group A, 417 +/- 282 ml; group B, 501 +/- 295 ml; group C, 605 +/- 333 ml; P <
      0.05), and postoperative complications (group A, 3.3%; group B, 5.6%; group C,
      22.0%). There were significant differences in postoperative complications between
      groups A and C, and between groups B and C. However, the difference between
      groups A and B was not significant, and no significant difference in survival
      rate was seen among the three groups.CONCLUSION: Fat volume definitely increases
      the postoperative complications. Accordingly, the high rate of postoperative
      complications of D2 surgery in Western countries may be related to the patients'
      relative obesity.

PMID- 11984728
TI  - Long-term results for patients with unresectable gastric cancer who received
      chemotherapy in the Japan Clinical Oncology Group (JCOG) trials.
AB  - BACKGROUND: Despite recent developments in chemotherapeutic trials, the long-term
      results of chemotherapy remain to be clarified. We evaluated the impact of
      chemotherapy on long-term survival in patients with unresectable gastric
      cancer.METHODS: Between 1985 and 1991, a total of 363 patients with gastric
      cancer were enrolled into a single randomized phase II study and into three
      series of phase II studies of the Japan Clinical Oncology Group. The chemotherapy
      regimens consisted of tegafur + mitomycin C (FTM), uracil-tegafur + mitomycin C
      (UFTM), 5'deoxy-flurorouridine + cisplatin (5'P), etoposide + doxorubicin +
      cisplatin (EAP), and 5-fluorouracil + cisplatin (FP). After a review of the 363
      patients' case records, 226 patients who fulfilled the criteria of having
      "unresectable" factors prior to chemotherapy became the subjects for this
      analysis. Of the 226 patients, 50 were in the FTM regimen group, 39, in the UFTM;
      49, in the 5'P; 42, in the EAP; and 46, in the FP group. Survival was updated
      continually.RESULTS: Of the 226 patients, 22 (10%) survived longer than 2 years,
      and 8 (4%) have survived longer than 5 years. The 8 5-year survivors consisted of
      6 patients who had para-aortic node metastases alone as an "unresectable factor",
      1 who had para-aortic and cervical node metastases, and the remaining patient who
      had liver metastasis alone. Twenty-nine patients with para-aortic node metastasis
      alone had a significantly longer survival than the other 197 patients ( P <
      0.001).CONCLUSION: Systemic chemotherapy may offer some hope of achieving long
      term survival in patients with unresectable gastric cancer, particularly when the
      patient has metastasis only to para-aortic nodes.

PMID- 11984729
TI  - Successful curative resection of gastric cancer with AIDS infection.
AB  - This report describes the case of a 47-year-old Japanese man with human
      immunodeficiency virus (HIV) infection with AIDS, who was successfully treated
      for gastric cancer. A review of gastric cancer associated with HIV is also
      presented. Prior to surgical treatment, azidothymidine (AZT), nerfinavir (NFV),
      and lamivudine (3TC) were administered to the patient in order to improve his
      blood CD4 count and reduce the viral burden. Consequently, distal gastrectomy was
      performed as a curative resection without any complications. The gastric cancer
      included a signet-ring cell carcinoma, as was noted in eight of the nine reported
      cases associated with HIV. This suggests that the HIV virus may play a role in
      causing signet-ring cell carcinoma, especially in the stomach.

PMID- 11984730
TI  - Surgically treated Cronkhite-Canada syndrome associated with gastric cancer.
AB  - Cronkhite-Canada syndrome is generally accepted to be a benign disorder, with 374
      reported cases to the present. Worldwide, there have been 18 previously reported
      cases of Cronkhite-Canada syndrome associated with gastric cancer. In this report
      we describe a case of a 52-year-old man with the clinical features of Cronkhite
      Canada syndrome combined with gastric cancer. Although the gastric tumor was
      located at the antrum of the stomach, we performed a total gastrectomy because of
      the edematous swelling and high risk of malignancy in the remnant stomach. As
      Cronkhite-Canada syndrome may be a premalignant condition for gastric cancer, as
      well as for colorectal cancer, we suggest periodic examination of the stomach,
      colon, and rectum for patients with Cronkhite-Canada syndrome.

PMID- 11984731
TI  - Benign gastric carcinoid tumor with hypergastrinemia followed up for 12 years.
AB  - Gastric carcinoid tumors associated with chronic atrophic gastritis type A have
      been reported to show good prognosis, because invasion and metastasis are rare.
      We report a case of gastric carcinoid tumor associated with hypergastrinemia that
      showed no malignant changes for 12 years. A 15-year-old man with abdominal
      discomfort underwent endoscopic examination. A polypoid lesion was detected on
      the atrophic mucosa of the fundus, and was diagnosed as a carcinoid tumor.
      Serological examination revealed a high level of anti-parietal-cell antibody,
      suggesting that the patient had chronic atrophic gastritis type A. The tumor was
      treated by endoscopic mucosal resection. Follow-up examinations were performed
      for 12 years, but showed no recurrence. This case confirms that gastric carcinoid
      tumors associated with chronic atrophic gastritis type A may have a good
      prognosis.

PMID- 11984732
TI  - Gastritis cystica polyposa associated with a gastric stump carcinoma, with
      special reference to cell kinetics and p53 gene aberrations.
AB  - We report a case of gastritis cystica polyposa (GCP) that developed in
      association with a small stump carcinoma. The patient had had distal gastrectomy
      for peptic ulcer 33 years prior to the present illness. Total gastrectomy was
      carried out for the stump carcinoma of the remnant stomach, followed by Roux-en-Y
      anastomosis. Histological examination revealed that the cancer was associated
      with a GCP lesion in its neighborhood. The resected stomach was subjected to a
      cell kinetics study and p53 gene analysis, as GCPs are thought to have a high
      potential for carcinogenesis. The GCP mucosae, as well cancer tissues and remnant
      mucosae obtained from the same specimens, were investigated and compared. We
      found that cell kinetics, as measured by a Ki-67 labeling index count, was more
      accelerated in the GCP than in the remnant mucosa, and that p53 gene aberrations,
      including both mutations and deletions, took place in the GCP lesion. As the p53
      gene is considered to be recessive, in principle, its tumor suppressive activity
      is lost only when gene aberration, either mutation or deletion, occurs
      concurrently or successively in both alleles. It was of interest to us that a
      benign lesion such as GCP had, in this instance, already developed both gene
      aberrations, strongly suggesting a precancerous nature for this disease.

PMID- 11984733
TI  - Advanced gastric carcinoma successfully treated with TS-1 as neoadjuvant
      chemotherapy.
AB  - We report a patient with advanced gastric carcinoma successfully treated with the
      novel oral fluoropyrimidine anticancer drug TS-1 as neoadjuvant chemotherapy. The
      patient was a 76-year-old man who had gastric cancer clinically diagnosed as
      N2T4, invading the pancreas, the duodenum, and the transverse colon. He was
      treated as an outpatient with TS-1, 120 mg, administered orally every day for 28
      days, followed by 14 days' rest, as one course. Two courses resulted in a marked
      reduction of the tumor without severe toxicity. Subsequently, the patient
      underwent curative surgery consisting of distal gastrectomy with D2 lymph node
      dissection. No surgical complications were observed. On microscopic examination,
      a few tumor cells were detected in the ulcer scar of the resected stomach and in
      the regional lymph nodes. Our report is the first to demonstrate the advantages
      of TS-1 as neoadjuvant chemotherapy for the treatment of advanced gastric
      carcinoma.

PMID- 11984734
TI  - Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with
      gastric cancer.
AB  - BACKGROUND: This clinicopathological study evaluated the utility of serum
      carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors
      of locoregional recurrence and long-term disease-free survival in patients with
      gastric cancer.METHODS: During the period January 1989 to December 1994, 485
      patients with primary gastric cancer were evaluated. Gastrectomies were performed
      in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and
      multivariate analysis, using Cox regression.RESULTS: Elevated serum CEA and CA19
      9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435
      patients (21.8%), respectively, and both markers were elevated in 29 of these 435
      patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph
      node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of
      invasion, and curability. Patients with elevated serum CEA levels were at
      significantly higher risk of having all recurrence factors than were those with
      normal serum CEA levels. Patients with elevated serum CA19-9 levels were at
      significantly higher risk of having peritoneal metastases and distant metastases
      than were those with normal serum CA19-9 levels. A significant difference in the
      cumulative survival curves of patients was demonstrated between those with
      elevated and those with normal serum CEA or CA19-9 levels, even for patients at
      the same disease stage (stage III). Patients with elevated levels of both markers
      had a significantly worse prognosis than patients in whom the levels of both
      markers were normal. In patients who underwent gastrectomy, elevated serum CEA
      levels either preoperatively or within 3 weeks after gastrectomy were associated
      with significantly worse prognosis than were normal levels. When the cutoff level
      of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis,
      and surgical stage grouping were selected as independent prognostic factors by
      multivariate analysis of 14 prognostic factors, using Cox regression.CONCLUSION:
      Serum CEA and CA19-9 levels provide additional prognostic information in patients
      with primary gastric cancer. In particular, an elevated serum CEA level provides
      additional prognostic information and is a useful indicator of curability in
      patients who undergo gastrectomy. Serum CEA level is an independent prognostic
      factor in patients with primary gastric cancer.

PMID- 11984735
TI  - Expression of transforming growth factor beta (TGF-beta) may contribute, in part,
      to the variations in histogenesis and the prevalence of peritoneal dissemination
      in human gastric carcinoma.
AB  - BACKGROUND: Alterations in the activity of transforming growth factor beta (TGF
      beta) in humans have been implicated in fibrosis, immunosuppression, development
      of cancer, and other disorders. Scirrhous gastric carcinoma is characterized by
      cancer cells that infiltrate rapidly in the stroma with extensive growth of
      fibroblasts and fibrous tissue. Hence, the majority of studies examining the role
      of TGF-beta in gastric carcinoma have focused on scirrhous carcinoma.METHODS: We
      undertook a retrospective immunohistochemical study of gastric carcinoma in order
      to characterize TGF-beta expression in malignant gastric lesions and to determine
      whether TGF-beta expression was related to disease progression.RESULTS: TGF-beta
      expression in scirrhous gastric carcinomas was significantly higher than that in
      nonscirrhous gastric carcinomas. In patients with advanced gastric carcinoma with
      surgically curative resection, TGF-beta expression was significantly higher in
      those patients who developed peritoneal recurrence after surgery than in those
      who did not develop such recurrence. Patients with TGF-beta expression-positive
      tumors had significantly poorer survival than did those with TGF-beta expression
      negative tumors ( P = 0.017). In addition, multivariate Cox proportional hazard
      model analysis showed that TGF-beta immunohistochemical status was an independent
      prognostic factor ( P = 0.0031).CONCLUSION: These data suggest that TGF-beta may
      contribute, in part, to the variations in histogenesis and to the prevalence of
      peritoneal dissemination in gastric carcinoma.

PMID- 11984736
TI  - Clinical significance of disordered beta-catenin expression pattern in human
      gastric cancers.
AB  - BACKGROUND: Beta-catenin plays two distinct roles, in intercellular adhesion by E
      cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the
      former role is tumor-suppressive, while the latter is oncogenic. We investigated
      the involvement of beta-catenin in the histogenesis and clinical outcome of
      gastric cancers.METHODS: The expression pattern of beta-catenin was evaluated in
      stomach and lymph nodes from 82 patients with gastric cancer by
      immunohistochemistry and Western blot. Its association with E-cadherin expression
      and clinicopathological factors, including histological type and postoperative
      survival, was examined.RESULTS: Beta-catenin expression was classified into two
      patterns, normal (23.2%; 19 patients) and disordered (76.8%; 63 patients), the
      latter being subclassified as overexpressed (7.3%; 6 patients) and reduced
      (69.5%; 57 patients). A disordered beta-catenin expression pattern was
      significantly correlated with diffuse type adenocarcinoma and deep tumor
      infiltration ( P = 0.0154), but was not associated with lymph node metastasis ( P
      = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered
      beta-catenin expression was significantly associated with reduced E-cadherin
      expression ( P < 0.0001). On univariate analysis, the beta-catenin pattern, as
      well as depth of invasion and lymph node metastasis, was associated with
      postoperative prognosis; however, only lymph node metastasis was an independent
      prognostic factor on multivariate analysis. Interestingly, different disordered
      patterns of beta-catenin expression, both overexpressed and reduced, were
      associated with E-cadherin reduction and poorer postoperative
      survival.CONCLUSION: Although disordered patterns of beta-catenin expression
      varied in gastric cancers, they were consistently associated with cancer
      progression.

PMID- 11984737
TI  - Prognostic factors in patients with advanced gastric cancer with macroscopic
      invasion to adjacent organs treated with radical surgery.
AB  - BACKGROUND: The prognosis of patients with gastric cancer with invasion to
      adjacent organs is poor. The prognostic factors of patients with advanced gastric
      cancer with macroscopic invasion to adjacent organs (T4) who were treated with
      radical surgery was determined in the present study.METHODS: A total of 86
      consecutive patients with advanced gastric cancer who underwent radical
      (potentially curable) gastrectomy with combined resection of other organs for
      macroscopic invasion to adjacent organs during surgery, were investigated. The
      organs invaded macroscopically were the pancreas in 43 patients, mesocolon in 29,
      liver in 7, transverse colon in 5, adrenal gland in 3, spleen in 1, diaphragm in
      1, and other organs in 5. The prognostic factors were evaluated by univariate and
      multivariate analysis.RESULTS: The cumulative 5-year survival rate of the
      patients treated by radical surgery with the combined resection of invaded organs
      was 35.0%. Multivariate analysis demonstrated that location of the tumor, lymph
      node metastasis, histological depth of invasion, and extent of lymph node
      dissection were significant prognostic factors in advanced gastric cancer
      patients treated by radical surgery with combined resection of adjacent organs
      for macroscopic invasion.CONCLUSION: For patients with macroscopic T4 gastric
      cancer located in the middle- or lower-third of the stomach, aggressive resection
      of invaded adjacent organs with extended lymph node dissection should be
      performed to improve long-term outcome.

PMID- 11984738
TI  - Gastric cancer with extragastric lymph node metastasis: multivariate prognostic
      study.
AB  - BACKGROUND: Although many authors have investigated the prognostic factors of
      gastric cancer, there are few comprehensive studies on the prognosis of patients
      with extensive lymph node metastasis. The aim of this study was to clarify the
      prognostic factors of gastric cancer with extragastric lymph node metastasis,
      using multivariate analysis.METHODS: The study population consisted of 121
      patients who had undergone radical gastrectomy and extended lymph node dissection
      (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined
      18 clinicopathologic factors, including the type of gastrectomy, tumor size,
      depth of wall invasion, status of lymph node metastasis, and stage of disease.
      Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and
      multivariate analysis was done using the Cox proportional hazards model.RESULTS:
      The overall 5-year survival rate was 32%, and the 5-year survival rate after
      curative gastrectomy was 37%. Overall survival rate was associated with the type
      of gastrectomy, stage of disease, operative curability, tumor size, depth of wall
      invasion, and anatomical distribution of positive nodes, whereas the survival
      rate after curative gastrectomy was correlated with the type of gastrectomy,
      stage of disease, tumor size, gross type, and depth of wall invasion. Independent
      prognostic factors were operative curability and depth of wall invasion, and
      survival after curative gastrectomy was influenced only by the depth of wall
      invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa
      [T3]).CONCLUSION: In patients with gastric cancer with extragastric lymph node
      metastasis, independent prognostic factors after gastrectomy were operative
      curability and depth of wall invasion. Long-term survival can be achieved when
      the patients have no serosal invasion (T1, T2) and are treated by curative
      gastrectomy.

PMID- 11984739
TI  - Incidence of lymph node metastasis from early gastric cancer: estimation with a
      large number of cases at two large centers.
AB  - BACKGROUND: The presence of lymph node metastasis (LNM) is the most important
      prognostic factor for patients with early gastric cancer (EGC). A D2 gastrectomy
      has been the gold standard treatment. Strict criteria for endoscopic mucosal
      resection have been widely accepted in Japan. There are some trials aimed at
      expanding the indications for local treatment, although there has not been a
      comprehensive review of the risk of LNM with the lesions of EGC.METHODS: We
      investigated 5265 patients who had undergone gastrectomy with lymph node
      dissection for EGC at the National Cancer Center Hospital and the Cancer
      Institute Hospital. Nine clinicopathological factors were assessed for their
      possible association with LNM.RESULTS: None of the 1230 well differentiated
      intramucosal cancers of less than 30 mm diameter regardless of ulceration
      findings, were associated with metastases (95% confidence interval [CI], 0-0.3%).
      None of the 929 lesions without ulceration were associated with nodal metastases
      (95% CI, 0-0.4%) regardless of tumor size. Similarly to findings for intramucosal
      cancers, for submucosal lesions, there was a significant correlation between
      tumor size larger than 30 mm and lymphatic-vascular involvement with an increased
      risk of LNM. None of the 145 differentiated adenocarcinomas of less than 30-mm
      diameter without lymphatic or venous permeation were associated with LNM,
      provided that the lesion had invaded less than 500 &mgr;m into the submucosa (95%
      CI, 0-2.5%).CONCLUSION: Based on our large series of cases, we have been able to
      clarify the risks associated with EGC and to propose expansion of the criteria
      for local treatment. However, accurate histological evaluation of the resected
      specimens is essential to avoid recurrence for such EGCs that should be cured.

PMID- 11984740
TI  - Advanced gastric glandular-endocrine cell carcinoma with 1-year survival after
      gastrectomy.
AB  - Primary gastric endocrine cell carcinoma (ECC) is extremely rare. In general,
      when it is advanced, gastric ECC causes extensive ulceration (type 2) and invades
      or metastasizes to other organs, frequently to the liver and sometimes to the
      lungs or bones, and carries a poor prognosis. We herein report a 67-year-old man
      with advanced gastric ECC of extensive-polypoid shape (type 1) but without
      distant metastasis, who underwent total gastrectomy and treatment with oral
      tegafur-uracil (UFT), and showed no sign of recurrence 1 year later.

PMID- 11984741
TI  - Role of endothelin in cardiovascular disease.
AB  - Endothelins are a family of peptides, which comprises endothelin-1 (ET-1),
      endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1
      is a peptide secreted mostly by vascular endothelial cells, the predominant
      isoform expressed in vasculature and the most potent vasoconstrictor currently
      known. ET-1 also has inotropic, chemotactic and mitogenic properties. In
      addition, it influences salt and water homeostasis through its effects on the
      renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic
      peptide and stimulates the sympathetic nervous system. The overall action of
      endothelin is to increase blood pressure and vascular tone. Therefore, endothelin
      antagonists may play an important role in the treatment of cardiac, vascular and
      renal diseases associated with regional or systemic vasoconstriction and cell
      proliferation, such as essential hypertension, pulmonary hypertension, chronic
      heart failure and chronic renal failure. Long-term anti-endothelin therapy may
      improve symptoms and favourably alter the progression of heart failure.
      Endothelin appears to participate in induction and progression of sclerotic renal
      changes, leading to progression to end-stage renal disease. Anti-endothelin
      therapy might offer additional benefits in the prevention of progression of
      chronic renal failure in addition to the known benefits of RAAS inhibition.
      Clinical trials have demonstrated potentially important benefits of endothelin
      antagonists for patients with essential hypertension, pulmonary hypertension and
      heart failure. Further studies are necessary to determine the role of anti
      endothelin therapy in the treatment of cardiovascular diseases and determine the
      different roles of selective receptor antagonism vs. mixed ET(A/B)-receptor
      antagonism in human diseases.

PMID- 11984742
TI  - Interaction of ACE inhibitors and AT(1)-receptor blockers on maximum blood
      pressure response in spontaneous hypertensive rats.
AB  - This study in spontaneous hypertensive rats (SHR) was designed to determine
      whether a greater fall in blood pressure (BP) could be achieved with the
      combination of an angiotensin-converting enzyme inhibitor (ACE-I) and an AT(1)
      receptor blocking drug than with higher doses of either drug alone. The peak
      effect of captopril occurred 3 4 hours post-dose and a plateau response was
      achieved with 10 mg/kg. The peak effect of losartan occurred 7 8 hours post-dose
      and a plateau response was achieved with 10 mg/kg. Increasing the dose of either
      drug caused no greater fall in BP, but increased the duration of the effect.
      Captopril, 10 mg/kg, administered with losartan 10 mg/kg caused a greater fall in
      BP than captopril or losartan, 20 mg/kg. This was present after acute doses or
      after one week of daily therapy. The combination of ACE-I and AT(1)-blocking
      drugs is more effective than either therapy alone and may be a useful combination
      to manage hypertension and/or cardiac failure.

PMID- 11984743
TI  - Hyperglycaemia-induced intrarenal RAS activation: the contribution of metabolic
      pathways.
AB  - Hyperglycaemia-induced activation of the renin-angiotensin system (RAS) has been
      observed in normal and diabetic humans. Our main objective was to determine
      whether the mechanism involved a physical or metabolic effect of glucose. First,
      Sprague-Dawley rats of the CD strain were given sequential intravenous (i.v.)
      doses of 0.01, 0.1, 1.0, and 3.0 mg/kg candesartan 30 minutes apart, in the
      presence of a continuous i.v. infusion of dextrose 20% in water (D20W). The 0.1
      mg/kg dose produced a maximal renal blood flow (RBF) response and was used
      thereafter. Another set of animals then received an infusion of either normal
      saline (NS), dextrose 5% in water (D5W) or dextrose 20% in water (D20W) for 2
      hours, followed by candesartan 0.1 mg/kg i.v. Finally, the response to
      candesartan 0.1 mg/kg i.v. during D20W infusion was compared with that during
      infusion of 2-deoxyglucose (2DG), a glucose analogue that competitively inhibits
      the glycolytic enzyme, hexokinase. RBF (electromagnetic flowmeter), blood
      pressure (BP), blood glucose, and urine glucose were monitored. There was no
      significant RBF response to candesartan on either NS (6.01 to 0.48 to 6.20 to
      0.49 ml/minute/g kidney; p=0.216) or D5W (7.63 to 1.20 to 7.58 to 1.39
      ml/minute/g kidney; p=0.965), whereas there was a significant response to D20W
      (6.64 to 0.59 to 7.46 to 0.67 ml/minute/g kidney; p=0.002). The RBF response was
      significantly enhanced by D20W compared with 2DG (change in RBF: 0.82 to 0.22 vs.
      -0.04 to 0.26; p=0.05), despite similar BP, blood glucose, and urine glucose.
      Glucose acts, at least in part, through intracellular utilisation to induce RAS
      activation, as manifested by an enhanced renal vascular response to an
      angiotensin II antagonist.

PMID- 11984744
TI  - Oxidative stress increases the expression of the angiotensin-II receptor type 1
      in mouse peritoneal macrophages.
AB  - Angiotensin II (Ang II) has been shown to accelerate atherogenesis, and the
      cellular Ang II type 1 (AT(1))-receptor mediates most of Ang II-induced pro
      atherogenic effects. In this study we have examined the effect of macrophage
      oxidative stress on cellular AT(1)-receptor expression. Mouse peritoneal
      macrophages (MPM) from apolipoprotein-E deficient (E(0)) mice at increasing ages
      (1 6 months) demonstrated an age-dependent increase in cellular lipid-peroxides
      (PD) content. In parallel, the AT(1)-receptor mRNA and protein levels both
      increased by up to 3.7-fold and 1.7-fold, respectively, in MPM from 6-month old
      mice compared with 1-month old mice. Vitamin E supplementation to E(0) mice
      significantly decreased the MPM PD content and macrophage AT(1)-receptor mRNA
      expression compared with placebo-treated mice. The role of oxidative stress in
      the cellular expression of AT(1)-receptors was further demonstrated by
      manipulation of macrophage glutathione content. Buthionine-sulfoximine, a
      glutathione synthesis inhibitor, increased MPM PD content and AT(1)-receptor mRNA
      expression, whereas L-2-oxothiazolidine-4-carboxylic acid, that contributes to
      glutathione synthesis, reduced macrophage PD and AT(1)-receptor mRNA expression.
      Incubation of MPM with oxidised low-density lipoproteins (LDL) led to a
      significant, dose-dependent and time-dependent increase in macrophage AT(1)
      receptor mRNA and protein expression, compared with control cells. In contrast,
      native LDL or acetylated LDL did not significantly affect macrophage AT(1)
      receptor mRNA expression. In conclusion, our findings suggest that oxidative
      stress in macrophages induces AT(1)-receptor expression. This phenomenon can
      stimulate the interaction of Ang II with macrophages and hence accelerate
      macrophage foam cell formation and early atherogenesis.

PMID- 11984745
TI  - Comparative effects of cilazapril, carvedilol and their combination in preventing
      from left ventricular remodelling after acute myocardial infarction in rats.
AB  - OBJECTIVES: To compare the effects of cilazapril, carvedilol and their
      combination in preventing left ventricular remodelling (LVRM) after acute
      myocardial infarction (AMI) in rats. METHODS: Twenty-four hours after left
      coronary artery ligation, 100 surviving AMI female Sprague-Dawley rats were
      randomly assigned to: (1) AMI control (n=25); (2) cilazapril (Cila, 1 mg/kg/day)
      (n=25); (3) carvedilol (Car, 1 mg/kg/day) (n=25), and (4) cilazapril (1
      mg/kg/day)+ carvedilol (1 mg/kg/day) (combination) (n=25) groups. A sham-operated
      group (n=17) was selected randomly as a non-infarction control. After four weeks
      of therapy with the drugs given by gastric gavage, haemodynamic studies were
      performed, following which the rat hearts were fixed and pathologically analysed.
      Rats with MI size <35% or >55% were excluded. Complete data were obtained in 64
      rats, comprising AMI control (n=13), Cila (n=12), Car (n=12), Combination (n=14),
      and sham-operated (n=13) groups. RESULTS: There were no significant differences
      in MI size between the four AMI groups (45.2 46.7%, p>0.05). Compared with the
      sham-operated group, left ventricular (LV) end diastolic pressure (LVEDP), volume
      (LVV), weight (LVW), septal thickness (STh) and right ventricular weight (RVW)
      were all significantly increased (all p<0.001) in the AMI group, while the LV
      pressure maximal rate of rise and fall ( dp/dt) was significantly decreased (all
      p<0.001). In comparison with the AMI group, LVEDP, LVV, LVW, STh and RVW were all
      significantly decreased, while dp/dt was significantly increased in the Cila,
      Car, and combination groups, with LVEDP and STh decreasing more in the
      combination group than in the two monotherapy groups (p<0.05 0.01). There were no
      significant differences in other variables between the three therapy groups.
      CONCLUSIONS: Cilazapril, carvedilol and their combination are all effective in
      preventing LVRM after AMI in rats, and in improving haemodynamics and LV
      function, with the combination therapy being superior to monotherapy in all
      respects.

PMID- 11984746
TI  - Forearm vasodilator response to angiotensin II in elderly women receiving
      candesartan: role of AT(2)- receptors.
AB  - The effects of angiotensin II (Ang II) and the Ang II type 2 (AT(2)) receptor
      antagonist, PD 123319, on forearm vascular resistance (FVR) were studied in
      elderly women during Ang II type 1 (AT(1)) receptor antagonist therapy. Eight
      women, aged 67 +/- 6 years, received the AT(1)-receptor antagonist, candesartan,
      8-16 mg once-daily for three weeks. FVR responses to intra-brachial arterial
      infusions of Ang II (8-32 ng/minute) during the co-infusion of PD 123319 (8
      microg/minute) or placebo were measured at the end of the second and third weeks
      in a randomised, double-blind, crossover study. Ang II produced dose-dependent
      reductions in FVR during both the placebo and PD 123319 infusions. However, FVR
      was significantly higher during PD 123319 infusions than during placebo
      infusions. Candesartan therapy unmasks a vasodilator response to Ang II in
      forearm resistance vessels of elderly women. AT(2)-receptor blockade increases
      FVR, but does not prevent vasodilator responses to Ang II, suggesting that other
      vasodilator mechanisms may also be involved.

PMID- 11984747
TI  - Acute and long-term effects of ACE inhibition on renal haemodynamics in
      glomerular and interstitial nephropathies.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are the drugs of
      choice for the treatment of hypertension in patients with non-diabetic
      nephropathies. However, not every trial has reported better results with ACE
      inhibitors (ACE-I) than with other drugs. This study investigates whether the
      acute and chronic effects of ACE inhibition on renal and glomerular haemodynamics
      are similar in glomerular and interstitial nephropathies. METHODS: We studied 20
      hypertensive patients, on their usual diet, with mild-to-moderate chronic renal
      failure secondary to non-diabetic nephropathy. After a three-week wash out
      period, we determined plasma clearances of para-amino-hippurate and inulin
      before, and after acute oral administration of either enalapril or ramipril. This
      same test was carried out after one and two years of treatment with the same
      drug. RESULTS: Acute ACE inhibition causes a decrease of renal perfusion,
      glomerular filtration and pressure with an increase of afferent resistances. Long
      term ACE inhibition is associated only with a decrease in renal perfusion, with a
      non-significant tendency to higher filtration fraction and lower afferent
      resistances. All the renal haemodynamic modifications mentioned above are present
      only in patients with glomerular diseases. CONCLUSIONS: Renal and glomerular
      haemodynamic responses are not similar after acute and chronic ACE inhibition.
      Only patients with glomerular diseases show acute or long-term responses to ACE
      inhibition.

PMID- 11984748
TI  - Strain differences in angiotensin-converting enzyme and angiotensin II type I
      receptor expression. Possible implications for experimental chronic renal
      transplant failure.
AB  - BACKGROUND: The Fisher to Lewis (F-L) model of renal transplantation (Rtx) is
      widely used. Rtx from F to L without immunosuppressive treatment results in 50%
      survival, whereas L to F results in survival rates similar to syngrafts. When
      treated with an angiotensin-converting enzyme (ACE) inhibitor or antihypertensive
      triple therapy, renal damage is markedly reduced in F-L allografts. Despite
      similar reductions in blood pressure, the ACE inhibitor (ACE-I) is more effective
      than antihypertensive triple therapy, suggesting that the inhibition of
      intrarenal ACE plays an additional role in the attenuation of renal damage.
      METHODS: In the present study, we investigated strain-related differences in
      intrarenal ACE activity between F and L rats and whether treatment with ACE-I in
      F-L allografted rats results in reduction of intrarenal ACE. Intrarenal ACE was
      measured by activity assays, immunohistochemistry and PCR. RESULTS: In control
      kidneys from healthy F rats (n=8), we found a four-fold higher ACE activity than
      in native L rats (n=8, p<0.01). This was confirmed by a three-fold difference in
      ACE mRNA expression (n=5 for both, p<0.01). Using immunohistochemistry, we found
      strong tubular ACE expression in the F rat, whereas the L rat had no tubular ACE
      at all. In F-L allografts (n=9) we noted significant glomerulosclerosis and
      proteinuria after 34 weeks. Treatment with ACE-I in F-L (n=8) prevented the
      development of these changes. Although ACE mRNA and ACE protein expression were
      similar in treated and untreated allografts, intrarenal ACE activity was reduced
      by 50% in allografts with ACE-I. CONCLUSION: In conclusion, intrarenal levels of
      ACE may play a role in the development of renal damage in experimental chronic
      renal transplant failure.

PMID- 11984749
TI  - The renin-angiotensin system does not contribute to the endothelial dysfunction
      and increased infarct size in rats exposed to second hand smoke.
AB  - INTRODUCTION: Both second hand smoke (SHS) and the renin-angiotensin system (RAS)
      contribute to endothelial dysfunction and increased infarct size in a rat
      ischaemia-reperfusion model. However, the potential interaction between SHS and
      the RAS is unknown. METHODS: Eighty-four rats were randomised into four groups:
      group C was a normal control; L was given 40 mg/kg/day of losartan in drinking
      water; SC and SL were exposed to SHS (smoking chamber) and given regular water or
      40 mg/kg/day of losartan in drinking water, respectively. After six weeks of pre
      treatment, rats were subjected to 17 minutes of left coronary artery occlusion
      and 2 hours of reperfusion with haemodynamic and ECG monitoring. RESULTS:
      Haemodynamics were not significantly different among the four groups. Losartan
      increased the threshold for ventricular fibrillation (p=0.0001) and reduced
      spontaneous ventricular arrhythmias (p=0.002) during ischaemia-reperfusion, while
      SHS did not (p=0.713, 0.110), and there was no interaction between losartan and
      SHS. The maximal endothelium-dependent vasorelaxation induced by a calcium
      ionophore (A23187) was increased by losartan (p=0.007). Myocardial infarct size
      was smaller in the losartan groups (p=0.032), larger in the SHS groups
      (p=0.0001), and there was no significant interaction. CONCLUSION: In conclusion,
      losartan decreased infarct size and increased endothelium-dependent
      vasorelaxation. SHS exposure impaired endothelial function and increased infarct
      size. The effects of losartan and SHS were consistently independent of each
      other. These results suggest that the RAS does not contribute to the adverse
      effects of SHS.

PMID- 11984750
TI  - Synthesis and stereochemistry of dispiro substituted pyridazines: application of
      ellipticity-absorbance ratio spectra for proving enantiomeric relationship by
      HPLC-CD/UV detection.
AB  - The aim of our study was to synthesize vinylic and pyrido-fused pyridazines with
      a spirano moiety and to investigate their stereochemistry by spectroscopic and
      HPLC analyses. The vinylic compounds 5 were obtained by Knoevenagel condensation
      of cyclohexylidene malonates 1 with pyridazinecarbaldehyde 2. Compound 5b
      exhibits geometric isomerism identified by NMR, HPLC, and X-ray methods. The
      thermal rearrangement reactions of compounds 5 easily led to the pyridopyridazine
      derivatives 6. In the case of 6b, possessing both central and axial chirality,
      both diastereomers and the respective enantiomers were detected. Their
      stereochemical relationships could be determined by HPLC-CD/UV analyses with
      application of anisotropy spectra in a novel way.

PMID- 11984751
TI  - Chromatographic enantioseparation by cycloalkylcarbamate derivatives of cellulose
      and amylose.
AB  - Cyclopentyl and (+/-)-exo-2-norbornylcarbamates of cellulose and amylose were
      prepared and their chiral recognition abilities as chiral stationary phases for
      high-performance liquid chromatography (HPLC) were evaluated. Among these
      carbamates, cellulose tris(cyclopentylcarbamate) and amylose tris((+/-)-exo-2
      norbornylcarbamate) showed particularly high chiral recognition, which is
      comparable to that of several well-known phenylcarbamate derivatives. The chiral
      recognition mechanism of cellulose tris(cyclohexylcarbamate), which was
      previously found to be an effective chiral stationary phase for HPLC, was
      investigated using NMR spectroscopy. The derivative dissolved in chloroform
      exhibited the chiral discrimination of several enantiomers in NMR as well as in
      HPLC. For example, the 1,1'-bi-2-naphthol enantiomers were distinctly
      discriminated in the (1)H, (13)C, and 2D-NOESY spectra.

PMID- 11984752
TI  - Theoretical CD spectrum calculations of the crown-ether aralkyl-ammonium salt
      complex.
AB  - Rotatory strengths of the alpha-(1-naphtyl)-ethylammonium perchlorate (NEA)
      phenazino-18-crown-6 ether molecular complex is determined theoretically by the
      coupled oscillator model and using ab initio random phase approximation (RPA) to
      describe local excitations on the chromophores. The computational results are
      compared to the experimental circular dichroism (CD) spectrum published
      previously. The good qualitative agreement between calculated and measured
      optical rotatory strengths allows one to assign the CD bands of the complex in a
      unique manner.

PMID- 11984753
TI  - Enantioselective conjugate addition of diethylzinc to cyclic enones catalyzed by
      copper complexes of methylene-bridged P-chirogenic diphosphines.
AB  - The copper-catalyzed enantioselective conjugate addition of diethylzinc to 2
      cyclohexen-1-one was investigated using (R,R)-bis-(t-butylmethylphosphino)methane
      (1c) as a chiral ligand. The reaction was carried out at 0 degrees C in THF
      toluene as the solvent system and in the presence of 1.2 mol% of CuOTf afforded
      (S)-3-ethylcyclohexan-1-one with 85% ee.

PMID- 11984754
TI  - Enantiomeric separation of a thiazolbenzenesulfonamide compound using packed
      column subcritical fluid chromatography.
AB  - Separation of enantiomers of a thiazolbenzenesulfonamide compound was performed
      on a Chiralpak AD column using subcritical fluid chromatography. Effects of
      alcohol modifier and temperature on the separations were studied. The results
      revealed that while the main adsorbing interactions were between the hydroxyl
      group of the analyte and the carbamate group of the stationary phase, chiral
      discrimination was achieved through an inclusion mechanism within the chiral
      cavity created along the amylose chains. Analogs and synthetic precursors of the
      thiazolbenzenesulfonamide studied were also investigated so as to understand the
      effect of functional groups and configuration of the analyte molecule upon chiral
      recognition.

PMID- 11984755
TI  - Determination of absolute configuration using vibrational circular dichroism
      spectroscopy: the chiral sulfoxide 1-thiochromanone S-oxide.
AB  - We reexamined the absolute configuration (AC) of the chiral sulfoxide 1
      thiochromanone S-oxide (1) using vibrational circular dichroism (VCD)
      spectroscopy. The VCD spectrum of 1 was analyzed using density functional theory
      (DFT). DFT predicts two stable conformations of 1, separated by <1 kcal/mole.
      Their VCD spectra were calculated using the DFT/GIAO methodology. The VCD
      spectrum predicted for the equilibrium mixture of the two conformations of (S)-1
      is in excellent agreement with the experimental spectrum of (+)-1. The AC of 1 is
      therefore definitively R(-)/S(+).

PMID- 11984756
TI  - First direct discrimination of chiral phosphine selenide (P=Se) derivatives by
      multinuclear magnetic resonance spectroscopy in the presence of a chiral
      dirhodium complex.
AB  - Enantiomeric ratios of compounds with P=Se functionalities (phosphine selenides)
      can easily be determined by (1)H, (13)C, (31)P, and (77)Se NMR spectroscopic
      inspection of their diastereomeric complexes with (R)-Rh(2)(MTPA)(4) (MTPA-H
      identical with methoxytrifluoromethylphenylacetic acid; Mosher's acid). This is
      the first facile and rapid spectroscopic method for chiral recognition in this
      class of compounds. Whereas most complexation shifts Delta(delta) are moderate or
      even negligible, significant signal dispersions Delta(nu) can be observed. Some
      rationalization for the adduct formation mode is presented. NMR spectral
      characteristics of the free P=Se compounds 1-5 are described.

PMID- 11984757
TI  - Axially dissymmetric (R)-(+)-5,5',6,6',7,7',8,8' octahydro
      [1,1']binaphthyldiimine chiral salen type-ligands for copper-catalyzed asymmetric
      aziridination.
AB  - Axially dissymmetric chiral diimine ligand 2 was prepared from the reaction of
      (R)-(+)-5,5',6,6',7,7',8,8'-octahydro-[1,1']binaphthyl-2,2'-diamine 1 with 2,6
      dichlorobenzaldehyde. The catalytic asymmetric aziridination of alkenes was
      examined using this novel chiral ligand. Excellent enantioselective aziridination
      of cinnamates was achieved using C(2)-symmetric chiral ligand 2.

PMID- 11984758
TI  - Recent applications of stereoselective chromatography.
AB  - Some recent applications of stereoselective chromatography in the fields of
      clinical pharmacy, drug analysis, food, and natural products are reviewed. The
      review is documented with up-to-date literature, which will assist further
      expansion of research in these areas.

PMID- 11984759
TI  - Pharmacokinetics of the active antifungal enantiomer, SCH 42427 (RR), and
      evaluation of its chiral inversion in animals following its oral administration
      and the oral administration of its racemate genaconazole (RR/SS).
AB  - Genaconazole (SCH 39304) is a potent triazole antifungal agent that is active
      both orally and topically. Genaconazole is a racemic mixture which contains 50%
      of the RR (SCH 42427) and 50% of the SS (SCH 42426) enantiomers. The RR isomer
      accounts for most of the antifungal activity of genaconazole. Serum
      concentrations of the RR and SS enantiomers were analyzed by a chiral HPLC method
      which involved extraction of serum with organic solvent followed by separation on
      a Cyclobond I column and quantification by UV absorbance at 205 nm. The
      bioavailability and pharmacokinetic profiles of the two enantiomers after oral
      administration of the racemate (genaconazole) were very similar in cynomolgus
      monkeys. In rats following dosing with genaconazole, the RR enantiomer had a
      lower C(max) and a longer t(1/2) than the SS enantiomer, while the AUC(I) values
      of the two enantiomers were similar. Based on chiral HPLC analysis, there was no
      evidence for the inversion of the RR to the SR isomer, or of the SS to the SR
      isomer, indicating that there was no chiral inversion of the RR or SS enantiomers
      in either species. Genaconazole at 20 mg/kg and the RR (SCH 42427) enantiomer at
      10 mg/kg had very similar serum concentration-time profiles and C(max), AUC(I),
      and t(1/2) values for the RR enantiomer in both rats and monkeys, indicating that
      the two treatments were equivalent with respect to the bioavailability of the RR
      enantiomer.

PMID- 11984760
TI  - Stereoselective kinetics of warfarin binding to human serum albumin: effect of an
      allosteric interaction.
AB  - Kinetic and equilibrium binding studies were performed on the interaction of
      warfarin enantiomers with human serum albumin (HSA) in the absence and presence
      of lorazepam acetate (LoAc) enantiomers. Binding kinetics were followed by
      recording changes in the fluorescence of warfarin upon binding to HSA using the
      stopped-flow technique. The binding of (R)-warfarin displayed an exponentially
      increasing fluorescence, satisfying the two-step mechanism reported previously
      for the racemate, i.e., a diffusion controlled pre-equilibrium is followed by a
      slower rearrangement of the complex. In the case of (S)-warfarin, the signal was
      biphasic: a fast fluorescence enhancement was followed by a slow decline. The
      different kinetic features indicate that the equilibrium conformations of the
      [(S)-warfarin-HSA] and [(R)-warfarin-HSA] complexes are achieved via different
      mechanisms. The phenomenon was seen in buffers of different pH and compositions.
      Equilibrium binding measurements indicated significantly lower molar intrinsic
      fluorescence for the (S)-warfarin complex, suggesting differences in the
      microenvironments of the bound enantiomers. In the presence of (S)-LoAc, the
      allosterically enhanced binding of (S)-warfarin manifested itself in accelerated
      relaxation kinetics. In accordance with the low molar intrinsic fluorescence
      determined for the stable ternary complex, the amplitude of the decline in
      fluorescence became larger.

PMID- 11984761
TI  - Chiral discrimination by HPLC and CE and antifungal activity of racemic
      fenticonazole and its enantiomers.
AB  - Fenticonazole is a chiral antifungal agent, used in therapy as the racemic
      mixture. The investigation on the chirality of fenticonazole is reported in this
      study. rac-Fenticonazole was resolved by HPLC and by capillary electrophoresis
      (CE). The chiral stationary phase (CSP), used in HPLC, was Daicel OD-H, a
      commercial phase, which allowed the separate collection of the two enantiomers.
      The chiral selectors used for CE were some cyclodextrin derivatives. The analysis
      time required from CE was about the half the HPLC enantioseparation time. The
      biological activity of the rac-mixture and each individual enantiomer was tested
      against Cryptococcus neoformans and two Aspergillus nidulans strains. The minimum
      inhibitory concentration (MIC) evaluation showed that the eutomer was the
      enantiomer chromatographically more retained and had a longer migration time in
      the electrophoretic enantioseparation. The CD spectrum of the eutomer showed a
      positive Cotton effect.

PMID- 11984786
TI  - Correlation between the sequential ingrowth of afferents and transient patterns
      of cortical lamination in preterm infants.
AB  - Transient patterns of regional, laminar, modular, neuronal, and functional
      organization are essential features of the developing cerebral cortex in preterm
      infants. Analysis of cytological, histological, histochemical, functional, and
      behavioral parameters revealed that transient cerebral patterns develop and
      change rapidly between 24 weeks post ovulation (W) and birth. The major afferent
      fibers (thalamocortical, basal forebrain, and corticocortical) grow through the
      transient "waiting" subplate zone (SP) compartment and accumulate below the
      cortical plate (CP) between 22 and 26 W. These afferent fibers gradually
      penetrate the CP after 26 W. The prolonged process of dissolution of the SP can
      be explained by prolonged growth and maturation of associative connections in the
      human cerebral cortex. The neurons and circuitry elements of the transient layers
      are the substrate for transient functional and behavioral patterns. The
      predominance of deep synapses and deep dendritic maturation underlies the
      immaturity and different polarity of the cortical electrical response in the
      preterm infant. The significant changes in the transient SP, together with
      profound changes in the transient architecture of the neocortical plate, parallel
      the changes observed in recent MRI studies. The role of the SP in the formation
      of cortical connections and functions is an important factor in considering the
      pathogenesis of cognitive deficits after brain lesions in the preterm infant.

PMID- 11984787
TI  - Calnexin is associated with and induced by overexpressed human complement protein
      C2.
AB  - C2 is a serum glycoprotein that is essential for activation of the classical and
      lectin pathways of the complement system. We reported previously that in
      transiently transfected COS cells, C2 accumulates in the endoplasmic reticulum
      Golgi intermediate compartment (ERGIC). Transfection with a cDNA corresponding to
      a variant C2 mRNA in which exon 17 is spliced out, C2Delta(17), resulted in
      retention of the mutant polypeptide in the ER. We now show that calnexin, a
      lectin-like chaperone, colocalizes with wild-type (wt) C2 and C2Delta(17).
      Biosynthetic labeling and sequential immunoprecipitation experiments indicated
      that colocalization is due to a physical association between calnexin and C2.
      Immunofluorescence analysis indicated that calnexin was upregulated in cells
      transfected with either C2 species. Upregulation of calnexin was not affected by
      castanospermine, which inhibits glucosidases I and II. However, castanospermine
      inhibited translocation of calnexin to the ERGIC in wt C2 transfected cells.
      Upregulation of calnexin was also observed in cells transfected with the
      complement protein factor B, a glycoprotein with extensive structural and
      functional similarities to C2, but not in cells transfected with complement
      proteins C3 or factor D, which have no structural similarity to C2, and low or no
      glycan content, respectively. Calnexin upregulation by transfection with C2 or
      factor B, but not factor D, was also demonstrated by quantitative analysis of
      calnexin immunoprecipitates from biosynthetically labeled cells. Increased
      calnexin expression by overexpressed C2 and factor B appears to be triggered
      either by the high glycan content of these proteins or, since it also occurs in
      the presence of castanospermine, by shared features of the structure of these two
      proteins.

PMID- 11984788
TI  - Structure of the conus arteriosus of the sturgeon (Acipenser naccarii) heart. I:
      the conus valves and the subendocardium.
AB  - Sturgeons are bony fish that retain structural traits typical of the more
      primitive Chondrostei. From an evolutionary viewpoint, sturgeons are considered
      relic fish. However, they show remarkable ecological plasticity and are well
      adapted to contemporary environmental conditions. Although development of the
      cardiovascular system is critical for all organs and systems, and is affected by
      evolutionary changes, the structure of the sturgeon heart has been mostly
      overlooked. This is also true for the conus arteriosus, which, as in Chondrostei,
      is endowed with several rows of valves and a layer of contractile myocardium.
      This work reports on the structure of the valves, the endocardium, and the
      subendocardium of the conus arteriosus of the sturgeon (Acipenser naccarii)
      heart. It is part of a broader study that aims to cover the entire structure of
      the sturgeon heart. The conus arteriosus of 15 A. naccarii hearts, ranging in age
      from juveniles to sexually-differentiated adults, has been studied by
      conventional light, transmission (TEM), and scanning electron microscopy (SEM).
      In addition, maceration of the soft tissues with NaOH, and actin localization by
      fluorescent phalloidin has been used. The conus is a tubular chamber that arises
      from the right ventricular side and presents two constrictions at the conus
      ventricle and conus-aorta junctions. The conus is endowed with three rows of
      valves: one distal and two proximal. The segment of the conus located between the
      distal and the two proximal rows is devoid of valvular structures. The distal row
      has four leaflets, while the two proximal rows show the greatest variation in
      leaflet number, size, and shape. All leaflets have collagenous chordae tendineae
      arising from the free border and from the parietal side of the leaflets. The
      endocardium is a flat endothelium which shows a thick, irregular basement
      membrane. The leaflet body is formed by a loose connective tissue which blends
      with the subendocardium. The subendocardium is a connective tissue consisting of
      myofibroblasts, collagen, and elastin. It is divided into two distinct areas: one
      proximal, which shows little elastin and poorly organized collagen; and one
      distal, which is rich in elastin, with cells and extracellular fibers organized
      into layers that are oriented in alternative circumferential and longitudinal
      directions. The present report is the first systematic analysis of the structure
      of the sturgeon conus. Descriptions of the conus valves should recognize the
      existence of three valve rows only. The variability in valve morphology, and the
      loose structure of the leaflet tissue make it unlikely that the valves play an
      effective role in preventing blood backflow. In this regard, the ventricle-conus
      constriction may act as a sphincter. The subendocardium is an elastic coat
      capable of actively sustaining the tissue deformation that accompanies the heart
      contractile cycle. Further comparative studies are needed to provide deeper
      insight into the structural changes that accompany phyletic diversification.

PMID- 11984789
TI  - Adipogenic healing in adult mice by implantation of hollow devices in muscle.
AB  - In mammals, wound healing is thought to result in the formation of scar tissue,
      with the exception of bony healing after fractures. Here we describe a previously
      unknown pattern of wound healing in which adipose rather than scar tissue is
      formed. Adipogenesis is normally confined to the embryo, although there are
      several experimental models for adipogenesis with highly specific dietary,
      cytokine, matrix, sex, or age requirements. The adipogenic healing described in
      this work provides a simple and reproducible experimental mouse model for
      adipogenesis without these limitations. Mice received intramuscular implants of
      nylon mesh material. Fibrinous material impregnated implants and within 4 weeks
      was replaced with highly vascular granulation tissue, typical of wound healing.
      Also consistent with wound healing was a reduction in vascularity of the newly
      formed tissue over time (P < 0.05). Lipoblasts were prevalent in granulation
      tissue, reaching a maximum in week 2 (P < 0.001) but falling to very low levels
      by week 9. These cells matured to adipocytes, with intermediate forms being seen.
      The identity of lipoblasts and adipocytes was confirmed by Oil Red O staining and
      electron microscopy. Control experiments confirmed that adipogenesis was
      independent of the materials used as well as of the sex and age of the animals.
      Rather, adipogenesis appeared to be due to replacement of fibrinous material in a
      space created within muscle. It is possible that adipogenic healing represents an
      adaptation for limiting the formation of restrictive scar tissues within muscle,
      and that this is the basis for the formation of traumatic lipomas in humans.
      Also, muscle tissue is replaced by adipose cells, seemingly derived from
      pluripotential satellite cells, in several degenerative muscle conditions,
      suggesting a role for adipogenic healing in these conditions.

PMID- 11984790
TI  - Morphological effects in the mouse myocardium after methylenedioxymethamphetamine
      administration combined with loud noise exposure.
AB  - Early toxicity occurring during or immediately after 3,4
      methylenedioxymethamphetamine (MDMA, or "ecstasy") administration has not been
      investigated in detail, although in humans it is responsible for marked side
      effects, and even death. Acute toxicity induced by MDMA produces rhabdomyolysis
      involving the myocardium (myocytolysis). Cardiac symptoms, such as tachycardia,
      hypertension, and arrhythmia, are present to a variable extent in humans abusing
      ecstasy. In most cases, this substance is abused in the presence of loud noise,
      which may affect the myocardium. Despite the frequency of the concomitant
      exposure to ecstasy and loud noise, and the similarities between the early side
      effects of these two agents, to our knowledge no study has investigated the role
      of loud noise in modulating MDMA toxicity. Therefore, in the present study, we
      evaluated whether cardiac effects of MDMA administration following a typical
      "binging" pattern are enhanced by concomitant exposure to loud noise. We selected
      low doses of MDMA in order to avoid gross morphological alterations, or lesions
      detectable under light microscopy. The myocardial alterations observed were
      visible only at the ultrastructural level. We found a dramatic enhancement of
      alterations in the mouse heart upon MDMA administration during loud noise
      exposure. Remarkably, this enhancement was evident both as a decrease in the
      threshold dose of MDMA necessary to alter the myocardial ultrastructure, and as
      an increase in myocardial alterations produced by a higher dose of MDMA.

PMID- 11984791
TI  - Abdominal situs inversus in a Holstein calf.
AB  - Situs inversus is a rare congenital anomaly wherein the normal, left-right organ
      location is inverted. The anatomical inversion (heterotaxy) is usually detected
      in routine radiography or other medical interventions. A 5-month-old Holstein
      heifer calf was identified as a suspected situs inversus totalis during abdominal
      surgery. Following surgery the calf did not gain weight. On admission to the
      Ontario Veterinary Hospital, it was given a routine clinical examination and a
      detailed cardiovascular, Doppler ultrasound examination, which appeared normal.
      Because of declining health and chronic bloating in the heifer, euthanasia was
      performed. A detailed post-mortem dissection was carried out. No heart or lung
      anomalies were detected. Other thoracic organs were normal, except for a helical
      coil of the esophagus as it traversed the diaphragm. The rumen was located
      entirely on the right side of the abdomen and had a large area of adhesion to the
      parietal peritoneal wall. The left kidney was abnormally placed: retroperitoneal
      and cranial to the right. There were two spleens. The caudal vena cava was
      distended and twisted to the left. Thus the calf was situs inversus abdominalis.
      This suggests that the development of laterality in the early embryo may include
      both timing and positional regulation.

PMID- 11984792
TI  - Hominid cranial bone structure: a histological study of Omo 1 specimens from
      Ethiopia using different microscopic techniques.
AB  - The microstructure of a hominid cranial vault has not previously been studied to
      determine its tissue histology, and differences in comparison with that of modern
      humans. We selected the parietals of Omo-Kibish 1, regarded as one of the oldest
      (about 130,000 years old) anatomically modern humans, and Omo 1 (Howell), which
      is a very recent human (about 2,000 years old)-both from the same area of
      Ethiopia. A combination of macrophotography, polarizing microscopy in the
      incident and transmission illumination mode, and confocal laser scanning
      microscopy (CLSM) was employed to examine thin sections, as well as polished and
      unpolished block faces of unembedded bone fragments, to minimize specimen
      destruction as much as possible. The methods enabled remarkably detailed
      information on bone microstructure and remodeling to be gleaned from tiny
      fragments of bone. The best method for examining fossilized human bones was shown
      to be that of incident light microscopy, which was the least destructive while
      producing the most amount of information. Unless the above methods are used, bone
      filling minerals, such as calcite, can cause erroneous estimations of bone
      thickness, as observations with the naked eye or even a magnifying glass cannot
      determine the limit between the cortex and the diploe. This is particularly
      important for sciences such as paleoanthropology, in which, for instance, a thick
      cranial bone of Homo erectus may be confused with a pathological one of H.
      sapiens and vice versa. Cross sections of parietal bones revealed differences
      between Omo-Kibish 1 and Omo 1 (Howell) in diploic histology and in the relative
      thickness between the cortex and diploe, with the former specimen having an H.
      erectus ratio despite its H. sapiens gross anatomy. Omo-Kibish 1 may still retain
      some affinities with H. erectus despite its being classified as H. sapiens. Newly
      described histological structures, such as the reverse type II osteons, the
      multicanalled osteons, and the osteocytomata are presented here. A modern human
      skeletal anatomy does not necessarily imply a modern human cranial bone
      histology. The outer circumferential lamellae of cranial bones are in essence
      growth lines. Cranial histology of hominids may provide useful information
      concerning their taxonomy and life history, including such factors as growth
      rate, developmental stress, and diet.

PMID- 11984793
TI  - S100P expression in human esophageal epithelial cells: Human esophageal
      epithelial cells sequentially produce different S100 proteins in the process of
      differentiation.
AB  - Extracellular calcium ions (Ca(2+)) are important in regulating the
      differentiation of keratinocytes and squamous epithelial cells. To clarify the
      mechanisms involved in the differentiation of human esophageal epithelial cells
      (EECs), we used the primary culture of human EECs, which can be differentiated by
      increasing the concentration of extracellular Ca(2+), and tried to reveal the
      extracellular Ca(2+) inducible genes using a differential display (DD) method. We
      found that the calcium-binding protein S100P showed a Ca(2+)-inducible expression
      in the EECs. Our immunohistochemical study demonstrated that differentiated large
      EECs expressing S100P overlie immature proliferating cells which lack S100P
      immunoreactivity. S100P was detected in vivo in the suprabasal layers of the
      epithelium. These findings indicate that S100P expression is closely associated
      with differentiation of human EECs. We also investigated the expression of other
      S100 proteins, including S100A2, S100A6, and CAAF1 (S100A12), in human EECs. Most
      of the immature EECs were positive for S100A2 and S100A6, whereas the S100A12
      producing cells were similar to the S100P-producing cells. In vivo, S100A12 was
      strongly detected on all epithelial cells except for basal and proliferating
      cells. S100A2 was detected on all of the epithelial cells. S100A6 was
      preferentially seen in the cells of basal layers. These findings suggest that
      within EECs S100 proteins might play important roles in cell differentiation
      during specific stages. Among them, S100P expression is unique in that this
      protein is transiently expressed during the early stage of differentiation.

PMID- 11984794
TI  - Cholinergic and noncholinergic innervation of the smooth muscle layers in the
      bovine abomasum.
AB  - The intrinsic innervation of muscle layers in the mammalian gastrointestinal
      tract has been mainly studied in nonruminants. The aim of this study was to
      identify intrinsic motor neurones in the bovine abomasum that innervate the
      circular and longitudinal muscles. Circular (CMN) and longitudinal muscle motor
      neurones (LMN) were selectively labeled by application of the retrograde tracer
      1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) onto the
      muscle layers. The transmitter phenotype was determined by immunohistochemical
      detection of choline acetyltransferase (ChAT), nitric oxide synthase (NOS), and
      neurone-specific enolase (NSE). On average, the myenteric ganglia contained 61 +/
      19 NSE-positive cell bodies, of which 89% were ChAT-positive and 10% were NOS
      positive. Only 0.7% of NSE-positive neurones (41 of 5,777) contained both ChAT
      and NOS. Application of DiI onto the circular and longitudinal muscles revealed
      on average 60 +/- 27 (n = 4) and 68 +/- 36 (n = 4), respectively, labeled cell
      bodies in the myenteric plexus. For the circular and longitudinal muscles the
      proportions of ascending to descending neurones were 76 : 24% and 54 : 46%,
      respectively. While most ascending CMN were ChAT-positive (96%), 51% of the
      descending CMN were ChAT-negative. All ascending and 95% of descending LMN were
      ChAT-positive. It was concluded that cholinergic excitatory innervation is
      predominant in both muscle layers of the abomasum. Whereas the circular muscle
      receives cholinergic excitatory and nitrergic inhibitory innervation, the
      longitudinal muscle is only innervated by cholinergic pathways. This innervation
      pattern is different from that in gastric muscle layers in monogastric animals.

PMID- 11984795
TI  - Comparative anatomy of the buccinator muscle in cat (Felis domestica).
AB  - Published descriptions of the buccinator muscle of the cat (Felis domestica)
      differ from those for the same muscle in other mammals. Only an oral component of
      the muscle has been described in cats, not a buccal part. The purpose of this
      study was to identify the buccinator muscle in the cat and report on its
      anatomical features in detail. Dissections of the facial muscles were carried out
      on 12 specimens of adult cats (6 males and 6 females) that had been fixed with
      10% formalin. We then observed the facial muscles and traced their innervations,
      arteries, and veins under a binocular microscope. The buccinator muscle in the
      cat was identified underneath an orbicularis oris, arising from the lower buccal
      membrane and from the molar region of the alveolar border of the mandible. It was
      about 3 mm wide at its origin, 4 mm wide at its insertion, and about 11 mm in
      length from origin to insertion. This contrasts with humans, in whom the muscle
      arises not only from the mandible, but also from the maxilla. Apart from this
      difference, this muscle in cats displays the following similarities to the
      buccinator muscle of other mammals: 1) it is innervated by the facial nerve; 2)
      it supports the buccal membrane; 3) it seems to insert into the modiolus; 4) its
      bundles run antero-posteriorly; 5) the posterior part of the muscle is located
      medially to the masseter muscle; 6) the parotid duct, facial nerve, artery, and
      vein run lateral to the muscle; 7) it is located deeper than other facial
      muscles; and 8) the buccal nerve runs on its surface. These relationships are
      spatially similar to those of the buccinator muscle in mammals. This muscle may
      aid in mastication, including suckling, and in expelling air forcibly, like the
      buccinator in humans.

PMID- 11984796
TI  - Editorial: chemotherapy for retinoblastoma.

PMID- 11984797
TI  - In vitro drug resistance profile of Philadelphia positive acute lymphoblastic
      leukemia is heterogeneous and related to age: a report of the Dutch and German
      Leukemia Study Groups.
AB  - BACKGROUND: The t(9;22)(q34;q11) translocation leading to the Philadelphia (Ph)
      chromosome resulting in BCR-ABL gene fusion is associated with a poor prognosis
      in acute lymphoblastic leukemia (ALL). PROCEDURE: We studied the relation between
      t(9;22), determined by karyotype, fluorescence in situ hybridization (FISH) or
      polymerase chain reaction (PCR), and in vitro drug resistance, measured by the
      MTT assay, in precursor B-cell ALL at diagnosis. The findings in twenty-one Ph
      positive (Ph+) childhood common/precursorB (c/preB) cases were compared with 254
      Ph-negative (Ph-) ALL cases. RESULTS: A large range of LC(50) values was found
      within the Ph+ patients. Moreover, LC(50) values did not differ significantly
      between Ph+ and Ph- samples for prednisolone, dexamethasone, L-asparaginase,
      vincristine, anthracyclines, thiopurines, epipodophyllotoxins, and 4H00
      ifosfamide, even after matching for important prognostic features (age, white
      blood cell count (WBC), and immunophenotype). Adult Ph+ (n = 12) ALL was more
      resistant to prednisolone (> 270-fold, P = 0.030), and displayed an overall
      tendency to resistance when compared to matched cases of Ph- (n = 15) adult
      precursor B-cell ALL. Within Ph+ ALL, in vitro prednisolone resistance increased
      significantly with age (P = 0.006). The expression of lung resistance protein
      (LRP), but not P-glycoprotein (P-gp) or multidrug resistance protein (MRP), was
      significantly higher in all Ph+ patients. CONCLUSIONS: Both childhood and adult
      Ph+ precursor B-cell ALL samples display a heterogeneous in vitro resistance
      profile, with relatively sensitive and resistant cases. The adult Ph+ samples,
      however, are generally more resistant compared to matched Ph- controls, reaching
      significance for prednisolone. The correlation of prednisolone resistance with
      age within the Ph+ cases might help explain the poorer prognosis of adult Ph+
      ALL.

PMID- 11984798
TI  - Isolated extramedullary relapse in acute myeloid leukemia: A retrospective
      analysis.
AB  - BACKGROUND: Little is known about the characteristics and outcome of children
      with acute myeloid leukemia (AML) experiencing an isolated extramedullary relapse
      (IEMR). PROCEDURE: The tumor registry of The Children's Hospital of Philadelphia
      identified 215 patients with AML diagnosed between 1970 and 2000, of which 16
      (7.4%) experienced IEMR. Patient- and disease-related features and outcome of
      patients with IEMR and other patients with AML were compared. RESULTS: IEMR
      occurred a median of 4.5 months (1.5-74 months) from diagnosis. Male to female
      ratio was 4.3:1 in patients with IEMR and 1.1:1 in the other patients with AML (P
      = 0.048). Median age at diagnosis and median presenting WBC were not
      significantly different in patients with and without IEMR. Patients with IEMR
      were more likely to have extramedullary disease (EMD) at diagnosis (31 vs. 4.5%)
      (P =.002) and FAB M4 or M5 morphology (P =.0001). Leukemic cells in 7 of 13
      patients (54%) had t(11q23), inversion 16 or t(8;21) with IEMR compared to 21 of
      93 other patients (23%) (P = 0.166). Six of 16 (37.5%) patients survive a median
      of 4.5 years (range 1.5-15 years) after IEMR and there are 13 survivors (23%) of
      57 patients after marrow or combined relapse (P = 0.56). One survivor of IEMR
      received local irradiation and continued on maintenance therapy while the other
      five received chemotherapy, irradiation, and allogeneic marrow transplant in
      second or third remission. CONCLUSIONS: Patients with isolated EMR are typically
      young males with monoblastic or myeloblastic leukemia who present with EMD at
      diagnosis. Marrow transplant following chemotherapy and local radiotherapy offer
      the potential for long-term survival.

PMID- 11984799
TI  - Perinatal exposure to infection and risk of childhood leukemia.
AB  - BACKGROUND: A population-based case-control study was conducted to investigate
      the association between childhood leukemia and infectious exposures during
      pregnancy and early neonatal period. PROCEDURE: Children born and diagnosed with
      leukemia between 1973 and 1989 in Sweden (578 lymphatic, 74 myeloid) were
      selected as cases. One control was randomly selected for each case and
      individually matched by sex, month, and year of birth. Children with Down's
      syndrome were excluded. Exposure data were blindly abstracted from antenatal,
      obstetric, and other standardized medical records. Odds ratios (OR) and 95%
      confidence intervals (CI) were calculated by conditional logistic regression.
      RESULTS: A history of maternal infection was not significantly associated with
      childhood leukemia, OR = 1.25 (95% CI 0.95-1.65). Maternal lower genital tract
      infection significantly increased the risk of childhood leukemia, OR = 1.78 (95%
      CI 1.17-2.72), and especially for children over 4 years of age at diagnosis, OR =
      2.01 (95% CI 1.12-3.80). Neonatal infection was not associated with the risk of
      leukemia. The results remained unaltered after adjustment for potential
      confounders, and separate analyses for myeloid and lymphoid leukemia.
      CONCLUSIONS: We could document an association between exposure to maternal lower
      genital tract infection in utero, and a subsequent risk for childhood leukemia,
      which indicate the importance of an early exposure.

PMID- 11984800
TI  - Cytodifferentiation and clinical outcome after chemotherapy and radiation therapy
      for rhabdomyosarcoma (RMS).
AB  - BACKGROUND: Second-look surgery after therapy for rhabdomyosarcoma (RMS) may
      yield prognostic information regarding tumor responsiveness to treatment.
      Favorable outcome is suggested by tumor cells which have undergone maturation
      (cytodifferentiation). PROCEDURE: Specimens from patients treated on Intergroup
      RMS Study-IV (IRSG-IV) were studied before and after treatment. All patients
      received chemotherapy and most received radiation therapy. Post-treatment
      specimens were graded according to the quantity of tumor showing
      cytodifferentiation (0 = absent, 1 = mild, 2 = moderate, 3 = extensive).
      Proliferative activity by MIB-1, topoisomerase II-alpha, and p53 protein
      expression were measured. RESULTS: 19/31 cases from IRSG-IV were adequate for
      analysis. Six out of nineteen patients failed therapy within 1.3 years of
      treatment. Grade 3 cytodifferentiation was present in 10 cases (2 BRMS, 8 ERMS);
      none failed therapy. Grade 2 cytodifferentiation was present in 5 cases (1 ERMS,
      2BRMS, 2ARMS); 2 patients with ARMS failed therapy. Grade 0-1 cytodifferentiation
      was present in 4 cases (1 ERMS and 3 ARMS); all failed therapy. Proliferative
      activity by MIB-1 and topoisomerase II-alpha immunohistochemistry decreased or
      was unchanged after treatment for all ERMS/BRMS, and 4/5 cases of ARMS. p53
      immunohistochemistry showed no consistent pattern of reactivity. Sparse
      persistent tumor cells were present in 9/10 ERMS, 3/4 BRMS, 5/5 ARMS.
      CONCLUSIONS: Extensive cytodifferentiation is more commonly seen in ERMS/BRMS
      compared with less evidence for cytodifferentiation in ARMS suggesting
      fundamentally different mechanisms of cellular response to therapy in RMS. Sparse
      persistent tumor cells in post treatment ERMS/BRMS specimens does not appear to
      affect outcome.

PMID- 11984801
TI  - Prevalence of thrombophilia and central venous catheter-associated neck vein
      thrombosis in 41 children with cancer--a prospective study.
AB  - BACKGROUND: This study was designed to prospectively evaluate the prevalence of
      thrombophilia and central venous catheter-associated neck vein thrombosis in
      children with cancer. PROCEDURE: Children with cancer and central lines, treated
      at the National Hospital in Norway, were consecutively enrolled in the study.
      Biochemical analysis of thrombophilia and Doppler ultrasonography of neck veins
      were performed at inclusion, and ultrasonography was repeated 3-5 months later.
      We recorded systematically positive blood-cultures and days with intravenous
      antibiotics. In a subgroup of 13 patients with acute lymphoblastic leukaemia, the
      thrombophilia parameters were re-evaluated during asparaginase therapy. RESULTS:
      Forty-one children were included in the study and observed for a mean of 266 days
      (range 95-569 days). Eighteen patients (44%) developed venous thrombosis (VT),
      visualized by Doppler ultrasonography of the catheterized vein. Some clots were
      transient, but blood clots with diameters > 0.5 cm (n = 11) had a tendency to
      remain (P = 0.14). Twelve children (29%) were classified as thrombophilic at
      inclusion, with elevated serum levels of homocysteine and lipoprotein (a) as the
      most frequent alterations. Transient thrombophilia developed in all patients
      during asparaginase-therapy. Within the limitations of our study, we did not find
      any significant correlation between thrombophilia and development of VT, nor
      thrombosis and infectious disease. CONCLUSIONS: VT develops frequently in
      paediatric cancer patients with central lines, but the clinical implication of
      this observation remains to be clarified.

PMID- 11984802
TI  - Combined chemotherapy and local treatment in the management of intraocular
      retinoblastoma.
AB  - BACKGROUND: To assess the efficacy of chemotherapy (chemoreduction) plus local
      treatments as an alternative to external beam and enucleation for intraocular
      retinoblastoma. MATERIALS AND METHODS: A prospective study was performed on 21
      patients with retinoblastoma treated in our institution from September 1997 to
      December 2000 to study the ocular outcome of those 33 eyes. RESULTS: There were 9
      unilateral and 12 bilateral retinoblastoma cases. There were 12 eyes with Reese
      Ellsworth group I-IV and 21 eyes with group V. Among 33 eyes, nine eyes (27%)
      were initially managed by enucleation. The remaining 24 eyes (73%) were initially
      treated with chemoreduction (maximum of six cycles of carboplatin, vincristine,
      etoposide) or chemothermotherapy. Among those 24 eyes, 20 were successfully
      treated with local treatments (thermotherapy plus cryotherapy in 16 eyes and
      thermotherapy plus cryotherapy plus (125)I plaque radiotherapy in 4 eyes),
      enucleation eventually underwent in two eyes and was proposed but refused in one
      child with bilateral group V retinoblastoma. With a median follow-up of 21
      months, conservative management without external beam radiation was successful in
      all 12 eyes with group I-IV and in a total of 20/33 eyes (60%). Among the nine
      cases of unilateral retinoblastoma, eight were enucleated but among the 24 eyes
      with bilateral retinoblastoma, 19 (79%) were successfully treated with
      conservative therapy. CONCLUSIONS: It may be possible to eradicate viable tumor
      in all eyes with Reese-Ellsworth group I-IV retinoblastoma by chemoreduction
      followed by local treatments. Although 8 out of 21 eyes (38%) with group V
      retinoblastoma may be salvaged after chemoreduction and local therapies,
      enucleation remained the treatment of choice in those eyes with total retinal
      detachment and diffuse vitreous seeding.

PMID- 11984803
TI  - Topical topic: value of fine needle aspiration biopsy in childhood
      rhabdomyosarcoma: twenty-six years of experience in Slovenia.
AB  - BACKGROUND: Chemotherapy (Cht) for rhabdomyosarcoma (RMS) given before local
      treatment can prevent mutilating surgery and high-dose irradiation (RT). Fine
      needle aspiration biopsy (FNAB) can confirm the diagnosis and neoadjuvant
      treatment can start without delay. The purpose of our study was to assess the
      role of FNAB in the management of childhood RMS in Slovenia. PROCEDURE: A total
      of 78 children and young adults were included. FNAB provided the pre-treatment
      diagnosis in 37 and surgical biopsy in 41 patients. In 61 cases
      recurrent/metastatic disease was aspirated. Cytological diagnoses were compared
      to the original histological diagnoses. All case histories, cytological and
      histological material were reviewed and immunocytochemical staining performed
      when necessary. RESULTS: FNAB provided a correct diagnosis of malignancy in all
      37 primary tumours, a specific diagnosis of RMS was given in 29 (78%). With the
      use of immunocytochemistry during the last 15 years, the accuracy has risen to
      87%. FNAB provided the diagnosis of recurrence/metastasis in 57/61 cases. No
      complications of FNAB were noted. Review of histology reclassified five original
      diagnoses of RMS into one malignant rhabdoid tumour and four sarcomas NOS. In
      review of cytology we were able to sub classify 80% of RMS. CONCLUSIONS: FNAB is
      a safe method, which enables us to establish the pre-treatment diagnosis of RMS,
      and to some extent even its type, without delay. In our study, FNAB successfully
      replaced surgical biopsy in 87% of RMS patients during the last 15 years.
      Neoadjuvant Cht was started immediately, surgery was delayed and more
      conservative. Consequently, the risk for treatment sequelae was considerably
      reduced.

PMID- 11984804
TI  - International note: second malignant neoplasms in children: a multicenter study
      of the Polish Pediatric Leukemia/Lymphoma Group.

PMID- 11984805
TI  - Kasabach-Merritt syndrome in a neonate caused by a kaposiform
      haemangioendothelioma.

PMID- 11984806
TI  - Overview: chemotherapy for retinoblastoma: an expanding area of clinical
      research.

PMID- 11984807
TI  - Brief report: conservative treatment in unilateral retinoblastoma: a preliminary
      report.

PMID- 11984808
TI  - Brief report: chronic myelopathy after combined chemo-radiotherapy in a patient
      with relapsed mediastinal B-cell lymphoma.

PMID- 11984809
TI  - Brief report: transient mutism following posterior fossa surgery studied by
      single photon emission computed tomography (SPECT).

PMID- 11984810
TI  - Letter to the editor: neurofibromatosis type 1 (NF 1) associated with embryonal
      rhabdomyosarcoma of the orbit.

PMID- 11984811
TI  - Letter to the editor: acute myeloid leukemia in a patient surviving
      retinoblastoma.

PMID- 11984812
TI  - Letter to the editor: acute myeloid leukemia in a child with Goldenhar syndrome.

PMID- 11984813
TI  - Letter to the editor: osteogenic sarcoma--cutaneous metastases.

PMID- 11984814
TI  - Letter to the editor: tumor thrombus in a child with primitive neuroectodermal
      tumor.

PMID- 11984815
TI  - Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in
      the mouse brain.
AB  - Zinc maintains a diverse array of functions in the mammalian central nervous
      system as a key component of numerous enzymes, via its role in the activation of
      transcription factors, and as a neuroregulator, modulating neuronal receptors
      such as N-methyl-D-aspartate and gamma-aminobutyric acid. Zinc has a dark side,
      however, with massive influx of Zn(2+) to neurons considered to be a key factor
      in neuronal death secondary to ischemia and seizure. Several different putative
      zinc transporters, ZnT-1-4, have recently been identified and characterized.
      Among them, ZnT-1 has been suggested to play a key role in reducing cellular
      Zn(2+) toxicity. In the present study, we describe the regional and cellular
      distribution of ZnT-1 in the adult mouse brain using an antibody raised against
      the C-terminal domain of mouse ZnT-1. The distribution of ZnT-1 was compared to
      that of chelatable Zn(2+), visualized by means of neoTimm histochemistry or N-(6
      methoxy-8-quinolyl)-p-toluene-sulfonamide (TSQ) histofluorescence. Extracts from
      various brain regions specifically stained a 60-kDa peptide corresponding to the
      expected molecular weight of ZnT-1. The expression of ZnT-1 was highest in the
      cerebral cortex and cerebellum, moderate in the hippocampus, hypothalamus, and
      olfactory bulb, and lowest in the striatum and septum. In brain sections, ZnT-1
      immunoreactive neurons, in particular principle neurons, in the somatosensory
      cortex, hippocampus, and olfactory bulb, were closely related to synaptic Zn(2+).
      Robust ZnT-1 immunoreactivity was also observed in cerebellar Purkinje cells.
      Although the function of the protein in these cells is unclear, in the forebrain,
      ZnT-1 is strikingly present in cells and regions where significant Zn(2+)
      homeostasis is required. This finding suggests a protective role for neuronal ZnT
      1 in the context of both normal and pathophysiological activity.

PMID- 11984816
TI  - Distribution of postsynaptic GABA(A) receptor aggregates in the deep cerebellar
      nuclei of normal and mutant mice.
AB  - In the central nervous system, the aggregation of receptors is crucial for
      synapse formation and function. To study the role of presynaptic terminals in the
      maintenance of postsynaptic specializations, we analyzed the synaptic contacts
      between Purkinje cells and neurons of the deep cerebellar nuclei in two in vivo
      models: the Lurcher and Purkinje cell-deficient (PCD) mutant mice. These mutants
      lose their Purkinje cells at different postnatal stages. By using confocal
      scanner microscopy and immunohistochemistry, we studied the distribution of the
      alpha subunit of the gamma-aminobutyric acid (GABA)(A) receptor (GABA(A)Ralpha1)
      and gephyrin, one of its anchoring proteins, in relation to the distribution of
      presynaptic markers, glutamic acid decarboxylase (GAD), or synaptophysin. In
      Lurcher the distribution of GABA(A) receptor aggregates on the membrane of
      postsynaptic neurons was not affected by the important loss of GAD-positive
      terminals, whereas in PCD, the number of large GABA(A) receptor aggregates
      increased. In both mutants the number of aggregates of gephyrin decreased. Most
      of these remaining aggregates were clustered to form groups, some of which were
      in front of GAD-positive terminals. This study shows, for the first time, the
      localization of GABA(A)R alpha 1 in Lurcher and PCD mutant mice. It clearly
      establishes that GABA(A)R alpha 1 and gephyrin are differentially affected by
      deafferentation. Because the receptor aggregates are maintained while the
      gephyrin aggregates are lost, as a result some receptor aggregates are not
      associated with any gephyrin. These two postsynaptic components appeared to be
      regulated by different mechanisms.

PMID- 11984817
TI  - Development of convergent synaptic inputs to subpopulations of autonomic neurons.
AB  - Visceromotor neurons in mammalian prevertebral sympathetic ganglia receive
      convergent synaptic inputs from spinal preganglionic neurons and peripheral
      intestinofugal neurons projecting from the enteric plexuses. Vasomotor neurons in
      the same ganglia receive only preganglionic inputs. How this pathway-specific
      pattern of connectivity is established is unknown. We have used a combination of
      immunohistochemical, ultrastructural, and electrophysiological techniques to
      investigate the development of synaptic inputs onto visceromotor and vasomotor
      neurons in the celiac ganglion of guinea pigs. Functional synaptogenesis occurred
      primarily from early fetal (F30-F35) to midfetal (F36-F45) stages, after the
      neurochemical differentiation of vasomotor and visceromotor neurons but before
      establishment of their electrophysiological phenotypes. Intestinofugal inputs
      were detected only on presumptive visceromotor neurons located primarily in
      medial regions of the ganglion. The number of ultrastructurally identified
      synaptic profiles increased in parallel with functional synaptogenesis,
      especially in medial regions, where dendritic growth rates also were higher.
      However, the expression of immunoreactivity to choline acetyltransferase in the
      terminals of inputs was very low until late fetal stages, after functional
      transmission already had been established. These results show that peripheral
      intestinofugal neurons directly establish appropriate functional connections with
      their target visceromotor neurons simultaneously with the development of
      functional preganglionic inputs to both visceromotor and vasomotor neurons. It
      seems likely that synaptogenesis occurs independently of the neurochemical
      differentiation of the target neurons but is closely related to the pathway
      specific dendritic development of those neurons.

PMID- 11984818
TI  - Estrogen-induced dendritic spine elimination on female rat ventromedial
      hypothalamic neurons that project to the periaqueductal gray.
AB  - Neurons of the ventromedial hypothalamic nucleus (VMH) that project to the
      periaqueductal gray (PAG) form a crucial segment of the motor pathway that
      produces the lordosis posture, the hallmark of female rat sexual behavior. One
      suggested mechanism through which estrogen facilitates lordosis is by remodeling
      synaptic connectivity within the VMH. For instance, estrogen alters VMH dendritic
      spine density. Little is known, however, about the local VMH microcircuitry
      governing lordosis nor how estrogen alters synaptic connectivity within this
      local circuit to facilitate sexual behavior. The goal of this study was to define
      better the neuron types within the VMH microcircuitry and to examine whether
      estrogen alters synaptic connectivity, as measured by dendritic spine density, on
      VMH projection neurons. A retrograde tracer was injected into the PAG of
      ovariectomized rats treated with vehicle or estradiol. Retrogradely labeled VMH
      neurons were filled with Lucifer yellow, then immunostained for estrogen receptor
      alpha (ER alpha). VMH neurons that project to the PAG had more dendrites than
      functionally unidentified neurons. Additionally, VMH projection neurons could be
      subdivided into those located within the cluster of ER alpha-containing neurons
      and those medial to the cluster. Estrogen decreased spine density by 57% on the
      long primary dendrites of VMH projection neurons located within the ER alpha
      cluster but not on projection neurons medial to the cluster. Only 4% of the VMH
      projection neurons expressed ER alpha. These results suggest that estrogen may
      facilitate sexual behavior by decreasing spines selectively, via an indirect
      mechanism, on a subset of VMH neurons that project to the PAG.

PMID- 11984819
TI  - Distribution and morphology of nigral axons projecting to the thalamus in
      primates.
AB  - This study presents an analysis of the distribution and organization pattern of
      axons originating from the substantia nigra pars reticulata and projecting to the
      thalamus in monkeys. Biotin dextran amine was iontophoretically injected into
      different parts of the substantia nigra pars reticulata of monkeys (African green
      monkeys and macaques). In whatever part of the substantia nigra the injection was
      made, numerous axonal endings were found to be distributed within different
      thalamic regions: the ventral anterior nucleus and mainly its magnocellular part,
      the most ventromedial part of the ventral lateral nucleus, and the mediodorsal
      and parafascicular nuclei. Moreover, the nigrothalamic projection appeared to be
      topographically organized. Ten anterogradely labeled axons were reconstructed
      from serial sections. The axons terminated in three to six terminal fields per
      axon located in a relatively small portion of only one thalamic region. These
      terminal fields were variable in size and comprised 4-43 very thin, varicose
      branches. They consisted either of different axonal branches of the same axon or
      of different axons and covered 10-31 thalamic cell bodies. These findings
      demonstrate that the overall morphological organization of individual nigral
      axons is complex and allows single axons to influence thalamic neurons via a
      combination of divergent, convergent, and amplification processes.

PMID- 11984820
TI  - Expression of basal lamina protein mRNAs in the early embryonic chick eye.
AB  - Laminin, collagen IV, collagen XVIII, agrin, and nidogen are major protein
      constituents of the chick retinal basal lamina. To determine their sites of
      synthesis during de novo basal lamina assembly in vivo, we localized their mRNA
      expression in the eye during maximum expansion of the retina between embryonic
      day (E) 2.5 and E6. Our in situ hybridization studies showed that the expression
      pattern of every basal lamina protein mRNA in the developing eye is unique.
      Collagen IV and perlecan originate predominantly from the lens epithelium,
      whereas collagen XVIII, nidogen, and the laminin gamma 1 and beta1 chains are
      synthesized mainly by the ciliary body. Agrin, collagen XVIII, collagen IV, and
      laminin gamma 1 also originate from cells of the optic disc. The only basal
      lamina protein that is synthesized by the neural retina throughout development is
      agrin with ganglion cells as its main source. Some of the mRNAs have short,
      transient expressions in the retina, most notably that of collagen IV and laminin
      gamma 1, both of which appear in the ventral retina between E4 and E5. That most
      retinal basal lamina proteins originate from extraretinal tissues infers that the
      basal lamina proteins have to be shed from the lens, optic disc, and ciliary body
      into the vitreous body. The assembly of the retinal basal lamina then occurs by
      the binding of these proteins by cellular receptor proteins on the vitreal
      endfeet of the retinal neuroepithelial cells.

PMID- 11984821
TI  - Ultrastructural characterization of the accessory lobes of Lachi in the
      lumbosacral spinal cord of the pigeon with special reference to intrinsic
      mechanoreceptors.
AB  - The lumbosacral spinal cord of birds is unique among vertebrates in that
      segmentally organized accessory lobes protrude from the ventrolateral spinal cord
      into the vertebral canal. Recently, it has been suggested that these lobes may be
      part of an extralabyrinthine sense organ of equilibrium. For a better
      understanding of such a function, a complete analysis of the structural basis was
      performed by means of electron microscopy. The lobes consist of multipolar
      neurons, myelinated and unmyelinated axons, glia-derived glycogen cells, glial
      cells, and capillaries. The dorsal part of the lobe is covered by a loose mesh of
      pia mater. Ventrolaterally, an arachnoidal trabecle is in close contact with the
      lobe. Extracellular lacunae extend from the periphery deep into each lobe. The
      lacunae are separated from the subarachnoidal space by a loose mesh of processes
      of the glycogen cells with its basal lamina. The lacunae are filled by a network
      of processes of glycogen cells, glial cell, dendrites, and small axons. Both
      neuronal somata and dendrites are contacted by numerous axon terminals that form
      rather uniform synapses. Finger-like processes emerge from both the somata and
      the dendrites. The dendrites branch deeply into the extracellular lacunae and
      form lateral ramifications, which consist of narrow stalks with serially arranged
      bulbous portions, from which finger-like processes emerge. Finger-like processes
      are well-known elements in mechanotransduction. Glycogen cells and lacunae may
      contribute to transmission of hydrostatic pressure changes during movements of
      the body.

PMID- 11984822
TI  - Nigral and pallidal inputs to functionally segregated thalamostriatal neurons in
      the centromedian/parafascicular intralaminar nuclear complex in monkey.
AB  - In primates, thalamostriatal projections from the centromedian (CM) and
      parafascicular (Pf) nuclei are strong and organized according to a strict pattern
      of functional connectivity with various regions of the striatal complex. In turn,
      the CM/Pf complex receives a substantial innervation from the internal globus
      pallidus (GPi). In this study, we demonstrate that the substantia nigra pars
      reticulata (SNr) also provides a massive input to Pf in monkeys. These
      pallidothalamic and nigrothalamic projections provide routes whereby information
      can flow in functional loops between the basal ganglia and the intralaminar
      nuclear group. To understand better the anatomical organization and the degree of
      functional specificity of these loops, we combined retrograde and anterograde
      labeling methods from functionally defined regions of the striatum and GPi/SNr to
      determine the relationships between thalamostriatal neurons and basal ganglia
      afferents. Together with previous studies, our data suggest the existence of
      tightly connected functional circuits between the basal ganglia and the CM/Pf in
      primates: 1) A "sensorimotor" circuit links together the medial two-thirds of CM,
      the postcommissural putamen, and the ventrolateral part of the caudal GPi; 2) a
      "limbic" circuit involves the rostral one-third of Pf, the ventral striatum, and
      the rostromedial pole of GPi; and 3) an "associative"circuit exists between the
      caudal two-thirds of Pf, the caudate nucleus, and the SNr. An additional
      "associative" circuit that involves the caudate-receiving territory of GPi
      (dorsal one-third), the dorsolateral Pf (Pfdl), and the precommissural putamen
      was also disclosed. In conclusion, findings of this study provide additional
      evidence for the high degree of functional specificity of the thalamostriatal
      system through which CM/Pf may provide attention-specific sensory information
      important for conditional responses to the primate striatum.

PMID- 11984823
TI  - Central administration of neuropeptide FF (NPFF) causes increased neuronal
      activation and up-regulation of NPFF gene expression in the rat brainstem.
AB  - Neuropeptide FF (NPFF) is a morphine modulatory peptide that plays an important
      role in a wide variety of physiological functions, including those related to
      nociception and central autonomic regulation. NPFF fibers and cells have been
      shown to be discretely localized in key autonomic centers within the brain,
      including the brainstem nucleus of the solitary tract (NTS). Central applications
      of NPFF evoke a number of important biological effects through activation of
      central neuronal circuits whose identities remain unknown at present. NPFF
      administered in this manner may also be capable of up- or down-regulating its own
      gene expression. In this study, we investigated the effects of
      intracerebroventricular (i.c.v.) administration of NPFF on the activation and the
      gene expression of NPFF in NTS neurons. Conscious rats received saline or NPFF (8
      or 10 microg i.c.v.), with concomitant monitoring of arterial blood pressure.
      Brains were prepared for Fos immunohistochemistry to identify neuronal activation
      and NPFF in situ hybridization to determine cells expressing NPFF mRNA in the
      NTS. At a dose of 8 microg, i.c.v., NPFF did not evoke alterations in blood
      pressure, but, at 10 microg, there was an increase in arterial blood pressure of
      30-40 mmHg. Image analysis showed a dose-dependent increase in number of NPFF
      neurons that were activated in rats receiving i.c.v. NPFF compared with saline
      controls. NPFF gene expression in the NTS showed a similar dose-dependent
      increase following i.c.v. administration of either 8 or 10 microg of NPFF.
      Significantly greater numbers of activated neurons expressing the NPFF gene
      (double labeled) were observed in the NTS at the level of the area postrema in
      animals receiving i.c.v. NPFF compared with saline controls. These data indicate
      that centrally administered NPFF is capable of up-regulating its own gene
      expression in the NTS and that this effect appears in part to be independent of
      elevations in arterial blood pressure that this peptide can evoke when
      administered i.c.v. at the higher dose. The up-regulation of NPFF may play a
      homeostatic role in response to specific cardiovascular challenges, such as
      hypotension.

PMID- 11984824
TI  - Expression of matrix metalloproteinase -2, -9 and tissue inhibitors of
      metalloproteinase -1, -2, -3 mRNAs in rat uterus during early pregnancy.
AB  - Zymography and in situ hybridizition were used to investigate matrix
      metalloproteinase-2, -9 (MMP-2, -9) activities, and expression of mRNAs for MMP
      2, -9 and tissue inhibitors of matrix metalloproteinases (TIMP-1, -2, -3) in the
      rat uterus during early pregnancy (day 1-7). The zymography results showed two
      forms of MMP-2 (64 and 67 kDa) in the rat uteri during early pregnancy. The 64
      kDa MMP-2 activity was the highest on day 2 (P < 0.01) and higher on day 5 and 6
      (P < 0.05). The 67-kDa MMP-2 activity reached the highest on day 5 and 6 (P <
      0.01). The 64-kDa MMP-2 activity at the implantation sites was higher than those
      at interimplantation sites (P < 0.05). Furthermore, the 67 kDa MMP-2 can be
      converted to 64 kDa forms by incubation with p-aminophenylmercuric acetate (APMA)
      and trypsin in vitro. The 92-kDa MMP-9 activity was only detected on day 5 and 6
      of pregnancy (P < 0.01). In situ hybridization showed that on day 1-4 of
      pregnancy, both MMP-2 and TIMP-2 mRNAs were evidently localized in the basal
      stromal cells. On day 5, MMP-2 mRNA signals were decreased in the basal stromal
      cells and mRNA for TIMP-2 was expressed in the epithelial cells and subepithelial
      stromal cells. The mRNAs for MMP-9, TIMP-1, and -3 were mainly expressed in
      epithelial cells on day 1-5. At the implantation site on day 6, the mRNAs for MMP
      2, -9, TIMP-1, -2, and -3 were highly expressed in the primary decidual zone
      surrounding the implanting embryo, and in the whole decidualized stromal cells
      (the primary and secondary decidual zones) at the implantation site on day 7. The
      intensities of mRNAs for the TIMPs in decidualized stromal cells at the
      implantation site on day 6 and 7 were stronger than those for the MMPs. The weak
      mRNAs for MMP-2, -9, TIMP-1, and -3 but not TIMP-2 were also observed in the
      ectoplacental cone/trophoblastic cells of the implanting embryos. However, at the
      interimplantation sites on day 6 and 7, MMP-2, -9, TIMP-1, -2, and -3 mRNAs were
      weakly expressed in the epithelial cells, subepithelial stromal cells, and
      myometrium. The results suggested that the implanting rat embryo strongly induced
      MMP-2 and -9 proteins and gene expression for decidulization and embryo invasion,
      which were strictly controlled and balanced by the simultaneous expression of
      TIMP-1, -2 and -3.

PMID- 11984825
TI  - Expression and localization of angiogenin in placenta: enhanced levels at term
      over first trimester villi.
AB  - Human angiogenin, a 14-kDa non-glycosylated polypeptide with both angiogenic and
      ribonucleolytic activities, is implicated in angiogenesis, a complex process of
      proliferation and formation of new capillary blood vessels from existing blood
      vessels. Placental growth requires extensive angiogenesis, which develops its
      vascular structure in both fetal chorionic villi and maternal deciduas. In this
      study, we investigated the expression profiles of angiogenin in placental villi
      from early and late gestation at both mRNA and protein levels using explant
      cultures in vitro followed by RT-PCR, immunoblot, and immunohistochemical
      analyses. From functionally active placental explants, angiogenin was detected in
      conditioned media of all the samples from first trimester and term group. The
      mean levels of angiogenin produced by term villi were found to be 2.6-, 2.1-, and
      2.2-fold higher (P < 0.01) than first trimester villi at 24, 48, and 72 hr of
      culture, respectively. Expression profiles of angiogenin from term and first
      trimester villi seem to agree with its mRNA levels and immunoblot analysis; the
      expression in term villi was twice that in first trimester villi. The presence of
      angiogenin in placental villi and upregulation of its production towards term
      indicate that angiogenin production by the placenta is specific to the
      developmental stage. In conclusion, the observed changes in the localization and
      mRNA expression of angiogenin during placental development raise the possibility
      that it is involved in morphological and angiogenic changes in this endocrine
      organ vital to the successful fetal outcome during pregnancy.

PMID- 11984826
TI  - mdr1a deficiency corrects sterility in Niemann-Pick C1 protein deficient female
      mice.
AB  - Niemann-Pick type C disease is a progressive neurological disease with
      cholesterol storage in liver, and npc1-/- mice share these features and are
      sterile. We have searched for the cause of sterility and found normal
      folliculogenesis and progesterone levels but lack of implantation. Multiple drug
      resistance (MDR) P-glycoproteins are plasma membrane proteins implicated in the
      movement of drugs and lipids across membranes. Their functions are inhibited by
      progesterone, which has been shown to alter cellular cholesterol homeostasis and
      has implicated P-glycoproteins in the movement of cholesterol to the endoplasmic
      reticulum. We have introduced the mdr1a knockout into the npc1 mutant line. While
      the neurological disease continues at its usual rate, preventing the females from
      taking care of their litters, npc1-/-, mdr1a-/- females became fertile. Although
      the mdr1a P-glycoprotein co-localizes with caveolae, neither caveolin-1 nor npc1
      levels were significantly altered in the livers of double homozygotes. The
      absence of mdr1a was confirmed by immunoblotting, but npc1 deficiency was not
      associated with consistent changes in cerebellar mdr1a in mdr1a+/+ mice. The
      results show that a mdr1a mutation is an in vivo suppressor of female sterility
      in npc1 deficient mice.

PMID- 11984827
TI  - Induced thermotolerance in bovine two-cell embryos and the role of heat shock
      protein 70 in embryonic development.
AB  - Induced thermotolerance is a phenomenon whereby exposure to a mild heat shock can
      induce heat shock proteins (HSP) and other cellular changes to make cells more
      resistant to a subsequent, more severe heat shock. Given that the 2-cell bovine
      embryo is very sensitive to heat shock, but can also produce HSP70 in response to
      elevated temperature, experiments were conducted to test whether 2-cell embryos
      could be made to undergo induced thermotolerance. Another objective was to test
      the role of the heat-inducible form of heat shock protein 70 (HSP70i) in
      development and sensitivity of bovine embryos to heat shock. To test for induced
      thermotolerance, 2-cell bovine embryos were first exposed to a mild heat shock
      (40 degrees C for 1 hr, or 41 degrees C or 42 degrees C for 80 min), allowed to
      recover at 38.5 degrees C and 5% (v/v) CO2 for 2 hr, and then exposed to a severe
      heat shock (41 degrees C for 4.5, 6, or 12 hr). Regardless of the conditions,
      previous exposure to mild heat shock did not reduce the deleterious effect of
      heat shock on development of embryos to the blastocyst stage. The role of HSP70i
      in embryonic development was tested in two experiments by culturing embryos with
      a monoclonal antibody to the inducible form of HSP70. At both 38.5 degrees C and
      41 degrees C, the proportion of 2-cell embryos that developed to blastocyst was
      reduced (P < 0.05) by addition of anti-HSP70i to the culture medium. In contrast,
      sensitivity to heat shock was not generally increased by addition of antibody. In
      conclusion, bovine 2-cell embryos appear incapable of induced thermotolerance.
      Lack of capacity for induced thermotolerance could explain in part the increased
      sensitivity of 2-cell embryos to heat shock as compared to embryos at later
      stages of development. Results also implicate a role for HSP70i in normal
      development of bovine embryos.

PMID- 11984828
TI  - Outer egg coats of the marsupial conceptus: secretion and protein composition.
AB  - Little is known of the composition of the outer egg coats. We aimed to quantify
      secretion during embryonic development, identify precursor secreting cells and
      investigate protein composition. The study was based on 259 egg coats and 14
      reproductive tracts of 104 T. vulpecula undergoing natural and induced cycles and
      341 coats from 35 Sminthopsis macroura undergoing natural cycles. Following PAGE,
      Western blotting, and amino acid sequencing of egg coats, the short peptide
      sequences obtained from T. vulpecula and S. macroura coats were found to be
      dissimilar to each other and to any known protein. However, in T. vulpecula, S.
      macroura coat polyclonal antibody cross-reacted with coat precursors, suggesting
      similar epitopes, and showed mucoid precursors in secretory cells in oviduct
      epithelia and shell precursors in glands in the utero-tubal junction and uterus.
      Immuno-electron microscopy located shell coat precursors in various previously
      unidentified cell types, including pre-ovulatory apoptotic cells, early post
      ovulatory holocrine cells, and milk-producing cells, found at blastocyst stages.
      Ultrastructural and quantitative volumetric analysis of the intact shell coat
      suggested a second wave of secretion at the blastocyst stages in T. vulpecula.
      Despite differences in protein composition, it was concluded that marsupial egg
      coats are homologous to each other because of similarities in ultrastructure and
      time and location of secretion.

PMID- 11984829
TI  - Betaine is a highly effective organic osmolyte but does not appear to be
      transported by established organic osmolyte transporters in mouse embryos.
AB  - Betaine protects early preimplantation mouse embryos against increased osmolarity
      in vitro, functioning as an organic osmolyte. Betaine is effective at very low
      external concentrations, with half-maximal protection of 1-cell embryo
      development to blastocysts at approximately 50 microM, making it one of the best
      osmoprotectants for mouse preimplantation embryos. We performed studies designed
      to determine whether known high-affinity organic osmolyte transporters could
      account for the ability of betaine to act as an organic osmolyte in
      preimplantation embryos. We found no evidence in 1-cell embryos of transport by a
      betaine/GABA transporter (BGT1), the osmoregulated betaine transporter found in a
      number of cell types, as betaine and GABA did not inhibit each other's transport.
      Instead, all saturable GABA transport in embryos was apparently via the beta
      amino acid transporter. We also found that the glycine transporter, GLY, which
      mediates osmoprotective transport of glycine in early preimplantation embryos,
      does not appear to transport betaine. Finally, increased osmolarity did not
      induce any detectable System A amino acid transporter activity, which is
      osmotically-inducible in other cells and can transport betaine. There does
      appear, however, to be a saturable betaine transporter in 1-cell mouse embryos,
      as considerable 14C-betaine transport was measured which was substantially
      inhibited by excess unlabeled betaine. Our data imply that betaine functions as
      an organic osmolyte in embryos due to its saturable transport via a mechanism
      distinct from known osmolyte transporters. We propose that an unidentified high
      affinity betaine transporter may be expressed in early embryos and mediate
      transport of betaine as an organic osmolyte.

PMID- 11984830
TI  - Cysteamine supplementation during in vitro maturation and embryo culture: a
      useful tool for increasing the efficiency of bovine in vitro embryo production.
AB  - Cysteamine when added during in vitro maturation (IVM) or in vitro embryo culture
      (IVC) stimulates glutathione (GSH) synthesis and improves embryo developmental
      rates. This suggests that GSH synthesis is decreased in the in vitro produced
      embryo. The present study was carried out to evaluate if addition of cysteamine
      to culture medium at the same time, during IVM and IVC of bovine oocytes, may
      promote an overall improvement on the developmental rate and embryo quality.
      Oocytes were matured in TCM 199 supplemented with 10% (v/v) fetal calf serum,
      hormones, and 0 or 100 microM of cysteamine for 24 hr. After IVM, the oocytes
      were fertilized (day 0). Day 2 embryos (2-8 cell) were washed and transferred to
      fresh IVC medium supplemented with 0, 25, 50, or 100 microM of cysteamine and
      cultured for 48 hr. After this, embryos were cultured in IVC medium without
      cysteamine until day 8 of IVC. In the present study, we confirmed our previous
      results by demonstrating that the percentage of embryos that developed to the
      blastocyst stage was significantly higher (P < 0.05) when 100 microM of
      cysteamine was added during IVM, and this was further improved when 100 and 50
      microM of cysteamine where present during IVM and IVC, respectively (P < 0.05).
      After cryopreservation, no differences were observed on embryo development, but a
      significant increase on embryo hatching was found between unsupplemented and
      supplemented oocytes with 100 and 50 microM of cysteamine during IVM and IVC,
      respectively (P < 0.05). We can conclude that GSH synthesis stimulation during
      bovine IVM with cysteamine, concomitant with GSH stimulation during IVC, will be
      a useful and simple tool for increasing the efficiency of in vitro bovine embryo
      production.

PMID- 11984831
TI  - Relationship between adenylate cyclase sensitivity to follitropin and FSH
      receptor mRNA expression in the ovary of the lizard Podarcis sicula.
AB  - In mammals, gonadal functions are regulated by two pituitary gonadotropins,
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH), that interact
      with gonadal membrane receptors to activate adenylate cyclase. In comparison to
      mammalian systems, in squamate reptiles a reduced amount of information exists on
      gonadotropins and their related receptors. This study is aimed at clarifying if,
      in the lizard Podarcis sicula, the ovarian sensitivity to FSH is correlated to
      the reproductive cycle and to the expression of membrane receptors involved in
      the hormone recognition. The results demonstrate that the ovarian adenylate
      cyclase responsiveness to FSH parallels ovarian functions, being maximal during
      the ovulatory period. The ovarian sensitivity to FSH is also related to oocyte
      growth and vitellogenesis. Northern blot analyses reveal that the FSH receptor
      mRNA is maximally expressed in vitellogenic oocytes during the reproductive
      period. These results suggest that, in lizard ovary, hormone activation of
      adenylate cyclase is mediated by de novo synthesis of receptors specifically
      involved in FSH recognition. In lizards treated in vivo with FSH during the pre
      ovulatory period, adenylate cyclase becomes refractory to further FSH stimulation
      2 hr after treatment, but sensitivity to the hormone is restored after 2 weeks.
      Nevertheless, while the restored level of activity never exceeds that observed
      during the nonreproductive period, the expression level of FSH receptor mRNAs is
      significantly enhanced in these animals. These results suggest that in lizard the
      processes that regulate ovarian growth, vitellogenesis, and ovulation are
      controlled by a complex network of signals including gonadotropin, FSH receptor
      expression, and adenylate cyclase.

PMID- 11984832
TI  - Immunohistochemical detection of the retinoid acid receptors (RXR-alpha, -beta, 
      gamma) and Farnesoid X-activated receptor (FXR) in the marbled newt along the
      annual cycle.
AB  - Retinoid acid receptors (RXR-alpha, -beta, -gamma) and Farnesoid X-activated
      receptor (FXR) expression in the testis of the marbled newt were investigated
      with special attention to the changes during the annual testicular cycle, using
      light microscopy immunohistochemistry and Western blot analysis. The annual
      testicular cycle of the marbled newt (Triturus marmoratus marmoratus) comprises
      three periods: (a) proliferative period (germ cell proliferation from primordial
      germ cells to round spermatids, April-June); (b) spermiogenesis period (July
      September); and (c) quiescence period (interstitial and follicular cells form the
      glandular tissue, October-April). In the proliferative period, primordial germ
      cells and primary spermatogonia immunostained intensely to the three types of
      RXRs and also to FXR. In the other periods, immunostaining to these antibodies
      was weak or absent. Secondary spermatogonia stained weakly to the four antibodies
      in the proliferative period, and only to FXR, also weakly, in the spermiogenesis
      period. Immunoreactive primary spermatocytes were weakly labeled with the RXR
      antibodies in the proliferative period. Spermatids and spermatozoa did not stain
      to any antibody in any period. Follicular cells only immunostained to RXR-gamma
      and only in the quiescence period when they are forming the glandular tissue,
      together with the interstitial cells. As follicular cells, interstitial cells
      only immunostained in the quiescence period; however, they immunoreacted to the
      three types of RXRs. These findings suggest that in the newt, RXRs and FXR are
      involved in spermatogenesis control by regulating the proliferation of primordial
      germ cells and spermatogonia. In addition, RXR-gamma seems to be also involved in
      the development of the glandular (steroidogenic) tissue.

PMID- 11984833
TI  - Stage-specific expression of proprotein form of hyaluronan binding protein 1
      (HABP1) during spermatogenesis in rat.
AB  - The presence of the 34-kDa hyaluronan binding protein 1 (HABP1) on sperm surface
      and its role in fertilization is already established (Ranganathan et al., 1994:
      Mol Reprod Dev 38:69-76). In the present communication, we examined the
      expression of HABP1 in adult rat testis during spermatogenesis. Interestingly,
      using anti-rHABP1 antibody, we detected a protein of 55 kDa which was present
      only in testis, but not in other somatic tissues like spleen and liver. However,
      even in testis, only one transcript of HABP1 mRNA of 1.63 kb was observed. In
      addition, we confirm that this testis-specific 55 kDa protein was immunologically
      identical with proprotein form of HABP1 using antibody raised against a
      decapeptide present in the proprotein region of HABP1. Comparative
      immunohistochemistry of testis, spleen, and liver tissues using both the
      antibodies supported the observation that the proprotein form of HABP1 is present
      only in testis. Higher mRNA expression of HABP1 in testis as compared to that of
      liver and spleen could be speculated from the RT-PCR product. Finally, detailed
      study of the immunohistochemical staining of the seminiferous tubules revealed
      the expression of the HABP1 proprotein in specific stages of germ cells, like
      pachytene spermatocytes and round spermatids, but not in elongated ones,
      suggesting a possible role of HABP1 proprotein in spermatogenic differentiation.

PMID- 11984834
TI  - A novel asparaginase-like protein is a sperm autoantigen in rats.
AB  - A novel asparaginase-like protein (ALP) of spermatozoa was cloned from rat and
      human testis cDNA libraries on the basis of reactivity with antibodies produced
      after vasectomy. Although obstruction of the male reproductive tract is known to
      cause an immunologic response, few of the sperm antigens responsible for the
      generation of autoantibodies have been characterized. We are identifying proteins
      of interest by coring autoantigenic protein spots from two-dimensional (2-D) gels
      of rat sperm extracts and microsequencing them by mass spectrometry. The peptide
      sequences from ALP, a 28 kDa, pI 5.7 protein, matched to a single partial length
      rat EST. These peptide sequences were used to clone a cDNA encoding a novel 333
      amino acid open reading frame. The new protein had a similarity to portions of L
      asparaginases of plants (43%) and to glycosylasparaginases in animal cells (32%).
      Human ALP cDNA was subsequently cloned. It showed 77% identity to the rat ALP
      sequence and the gene, ASRGL1 (asparaginase-like 1), mapped to chromosome locus
      11q12.3. Purified recombinant rat ALP (rALP), expressed in E. coli, was used to
      raise polyclonal antiserum in guinea pigs. Two observations verified that the
      correct protein had been cloned: 1) the anti-rALP antibody reacted with both rALP
      and rat sperm; and 2) post-vasectomy sera bound rALP. Anti-rALP antibody stained
      the midpiece of rat and human sperm coincident with staining by MitoTracker Green
      FM, suggesting that ALP is associated with the mitochondria. Northern analysis
      revealed that rat ALP message was abundantly expressed in the testis but was also
      present in heart, brain, liver, skeletal muscle, and kidney.

PMID- 11984835
TI  - In vivo versus in vitro oviductal glycoprotein (OGP) association with the zona
      pellucida (ZP) in the hamster and baboon.
AB  - The goal of this study was to determine if differences exist between in vivo vs.
      in vitro OGP association with the ZP and to quantitate those differences. Ovarian
      oocytes were harvested 12.5 or 27 hr post-hCG from hyperstimulated hamsters or
      baboons, respectively. Hamster and baboon ovarian oocytes were incubated in vitro
      in media +/- homologous OGP (100 or 200 microg/100 microl) or in some studies
      with 100 microl oviductal fluid for 3, 6, or 24 hr at 37 degrees C. Some of the
      baboon ovarian oocytes were transferred immediately after harvesting to the
      ampulla of both oviducts using a tom cat catheter and retrieved after a 3 hr in
      situ incubation. Hamster oviductal oocytes were collected 3, 6, and 24 hr
      following ovulation. After incubation or oocyte retrieval from the oviduct,
      cumulus cells were removed, oocytes were washed extensively and binding of OGP to
      the ZP was examined by immunofluorescence. Fluorescence intensity was quantified
      using densitometric scanning of photographic negatives with the background of
      each negative as an internal control. In all studies, OGP association with the ZP
      was significantly greater in vivo than in vitro (P < 0.05). In vitro OGP
      association with the ZP did not significantly increase with incubation time or
      OGP concentration; however, a small nonsignificant increase in OGP association
      with the ZP in the oviduct was detected over time. Differences did not appear to
      be due to depletion of OGP from the in vitro incubation media, since Western blot
      analysis of the media showed that OGP was still present. Although OGP
      concentration in vivo is unknown, Western blots showed similar intensity
      comparing 100 microg of OGP media and oviductal fluid. Immunolocalization of OGP
      using laser confocal microscopy showed regional differences in OGP binding. The
      outer half of the zona pellucida had significantly more OGP bound than the inner
      half on oviductal oocytes. No regional differences were detected for in vitro
      incubated oocytes. In conclusion, OGP association with the ZP is greater in vivo
      vs. in vitro, suggesting that one must be cautious in designing and evaluating in
      vitro studies of OGP function.

PMID- 11984836
TI  - Immunization of female cynomolgus macaques with a synthetic epitope of sperm
      specific lactate dehydrogenase results in high antibody titers but does not
      reduce fertility.
AB  - Previous studies have reported reduced fertility in female baboons immunized with
      a synthetic peptide derived from the sperm-specific isozyme of lactate
      dehydrogenase (LDH-C). In this study, a similar approach was used to immunize
      female cynomolgus macaques with the same peptide sequence (bC5-19) conjugated to
      a T-cell epitope from tetanus toxin (TT). Twelve female monkeys were immunized
      with bC5-19:TT delivered with Ribi MPL adjuvant vehicle, and 10 control female
      monkeys were injected with the adjuvant vehicle only. All 12 females in the
      treatment group developed LDH-C-specific serum antibodies as measured by ELISA,
      but anti-LDH-C antibodies were not detected in vaginal fluids of the immunized
      animals. After 4 months of timed mating immediately following the immunizations,
      five of the ten immunized females became pregnant, as did six of the ten control
      females. Anti-sera from both pregnant and nonpregnant bC5-19:TT-immunized females
      recognize a single band at 35 kDa on Western blots of whole sperm extracts, and
      purified Igs from the same sera localize along the principle piece of the
      flagellum of permeabilized sperm.

PMID- 11984837
TI  - Creatine phosphokinase in domestic cat epididymal spermatozoa.
AB  - Mammalian spermatozoa that have not completed final testicular sperm maturation
      have residual cytoplasm and increased creatine phosphokinase (CK) content. This
      study determined: (1) if CK could be detected by immunostaining cat spermatozoa
      from the caput, corpus, and cauda epididymis, (2) fluctuations in the proportions
      of spermatozoa with mature or immature CK-staining patterns during epididymal
      sperm transit, and (3) how well sperm maturity (as determined by a CK marker)
      correlated with testicular or epididymal dysfunctions associated with
      morphological sperm abnormalities. One epididymis was collected from each of 37
      cats after orchiectomy and processed immediately to allow sperm morphology
      evaluations on a 'regional' basis. Sperm released from the contralateral
      epididymis were evaluated for motility, sperm membrane integrity, and
      immunostaining with CK-B antibodies. Proportions of spermatozoa with malformed or
      detached heads, proximal droplets and acrosomal or midpiece abnormalities
      decreased (P < 0.05) from the caput to the cauda epididymis. In contrast,
      proportions of spermatozoa that were motile, membrane-intact or with flagellar
      abnormalities or distal droplets increased (P < 0.05) from the caput to cauda
      region. Percentages of spermatozoa with an immature CK-staining pattern also
      decreased (P < 0.05) with epididymal transit (which differs from that reported
      for the human and stallion). There was no correlation (P > 0.05) between sperm
      morphology and the CK-staining patterns. In summary, the results reveal that some
      specific sperm malformations in the domestic cat are of testicular origin,
      whereas others develop during epididymal transit.

PMID- 11984838
TI  - Localization and roles in fertilization of sperm proteasomes in the ascidian
      Halocynthia roretzi.
AB  - We previously reported that sperm proteasome is responsible for degradation of
      the ubiquitinated vitelline-coat during fertilization in the ascidian Halocynthia
      roretzi. Here, we report the roles in fertilization and localization in the sperm
      cell surface of H. roretzi sperm proteasome. An anti-proteasome antibody, as well
      as the proteasome inhibitors MG115 and MG132, inhibited the fertilization,
      indicating that the sperm proteasome functions extracellularly in ascidian
      fertilization. In order to further assess this issue, the sperm surface
      proteasome activity was labeled with a cell-impermeable labeling reagent, NHS-LC
      biotin, extracted with 0.1% CHAPS, and was subjected to a pull-down assay with
      avidin-agarose beads. It was found that a substantial amount of sperm proteasome
      is exposed to the cell surface. Partition analysis with Triton X-114 also
      revealed that a considerable amount of the sperm proteasome activity is
      partitioned into a lipid layer. Localization of the proteasome activity was
      investigated by fluorescence microscopy with succinyl-Leu-Leu-Val-Tyr-4
      methylcoumaryl-7-amide as a substrate. The sperm proteasome activity was
      specifically detected in the sperm head region, and it was markedly activated
      upon sperm activation. The membrane-associated proteasome was purified from the
      membrane fraction of H. roretzi sperm by affinity chromatography using an anti
      20S proteasome antibody-immobilized Sepharose column. SDS-PAGE of the purified
      preparation showed a similar pattern of subunit composition to that of the 26S
      proteasome of mammalian origin. Taken together, these results indicate that H.
      roretzi sperm has the membrane-associated proteasome on its head, which is
      activated upon sperm activation, and that sperm proteasome plays an essential
      role in H. roretzi fertilization.

PMID- 11984839
TI  - Checkpoint for DNA integrity at the first mitosis after oocyte activation.
AB  - Activation of oocytes, arrested at the meiosis II (MII) in mammals, initiates
      meiotic release, mitotic divisions, and development. Unlike most somatic cell
      types, MII arrested female germ cells lack an efficient DNA integrity checkpoint
      control. Here we present evidence showing a unique checkpoint for DNA integrity
      at first mitosis after oocyte activation. Mouse oocytes carrying intact DNA
      cleaved normally after meiotic release, whereas 50% of oocytes harboring damaged
      DNA manifested cytofragmentation, a morphological hallmark of apoptosis. If not
      activated, DNA-damaged MII oocytes did not show apoptotic fragmentation. Further,
      activated, enucleated oocytes or enucleated fertilized oocytes also underwent
      cytofragmentation, implicating cytoplasmic coordination of the fragmentation
      process, independent of the nucleus. Depolymerization of either actin filaments
      or microtubules induced no cytofragmentation, but inhibited fragmentation upon
      oocyte activation. During the process of fragmentation, microtubule networks
      formed, then microtubule asters congregated at discrete locations, around which
      fragmented cellular bodies formed. Mitotic spindles, however, were not formed
      inactivated oocytes with damaged or absent DNA; in contrast, normal mitotic
      spindles were formed in activated oocytes with intact DNA. These results
      demonstrate that damaged DNA or absence of DNA leads to cytofragmentation after
      oocyte activation. Further, we found a mechanism of cytoskeletal involvement in
      the process of cytofragmentation. In addition, possible implication of the
      present findings in somatic cell cloning and human clinical embryology is
      discussed.

PMID- 11984840
TI  - L1 mediated homophilic binding and neurite outgrowth are modulated by alternative
      splicing of exon 2.
AB  - The neural cell adhesion molecule (CAM) L1 is a member of the immunoglobulin
      superfamily that has been implicated in neuronal adhesion, neurite outgrowth, and
      axon guidance. The clinical importance of L1 is illustrated by pathological
      mutations that lead to hydrocephalus, mental retardation, motor defects, and
      early mortality. The L1 gene is composed of 28 exons, including exons 2 and 27
      that are spliced alternatively, and mutations in exon 2 are associated with
      severe neurological abnormalities in humans. To elucidate the role of L1 exon 2,
      a recombinant Fc fusion protein called Delta2L1 was constructed lacking the
      second exon in the extracellular domain of L1. When bound to fluorescent beads,
      L1 exhibited homophilic binding while Delta2L1 did not. However, L1 beads
      coaggregated with the Delta2L1 beads. Similarly, in cell binding studies, L1
      bound to L1 and Delta2L1 did not bind to Delta2L1 but it bound moderately to L1.
      Given the reduced binding of Delta2L1, we tested its effect on neurons. By
      comparison to L1, a lower percentage of dissociated neurons extended neurites on
      Delta2L1, and there was a modest decrease in the length of the neurites that
      grew. Neurite outgrowth from reaggregated neurons was much less robust on
      Delta2L1 than on L1. The combined results indicate that Delta2L1 does not bind
      homophilically but it can interact with L1 containing exon 2. The reduced binding
      and neurite promoting activity of Delta2L1 provides an explanation for certain
      pathological mutations in L1 that lead to clinically apparent disease in the
      absence of the normal form of L1 in the nervous system.

PMID- 11984841
TI  - Complementary expression and heterophilic interactions between IgLON family
      members neurotrimin and LAMP.
AB  - Neurotrimin (Ntm) and the limbic system-associated membrane protein (LAMP) are
      members of the IgLON (LAMP, OBCAM, Ntm) family of glycorylphosphatidylinositol
      anchored neural cell adhesion molecules. We previously reported that LAMP and Ntm
      promote adhesion and neurite outgrowth via a homophilic mechanism, suggesting
      that these proteins promote the formation of specific neuronal circuits by
      homophilic interactions. In this report, we have further characterized the
      expression and binding specificity of Ntm. Using a newly generated monoclonal
      antibody to Ntm, we demonstrated that this protein is largely expressed in a
      complementary pattern to that of LAMP in the nervous system, with co-expression
      at a few sites. Ntm is expressed at high levels in sensory-motor cortex and, of
      particular note, is transiently expressed in neurons of cortical barrel fields
      and corresponding thalamic "barreloids." Binding of a recombinant, soluble form
      of Ntm to CHO cells expressing either Ntm or LAMP demonstrates that Ntm and LAMP
      interact both homophilically and heterophilically. In contrast to conventional
      growth-promoting activity of Ig superfamily members, LAMP strongly inhibits the
      outgrowth of Ntm-expressing dorsal root ganglion (DRG) neurons in a heterophilic
      manner. These anatomical and functional data support the concept that homophilic
      and heterophilic interactions between IgLON family members are likely to play a
      role in the specification of neuronal projections via growth promoting and
      inhibiting effects, respectively.

PMID- 11984842
TI  - Forked end: a novel transmembrane protein involved in neuromuscular specificity
      in drosophila identified by gain-of-function screening.
AB  - The Drosophila neuromuscular connectivity provides an excellent model system for
      studies on target recognition and selective synapse formation. To identify
      molecules involved in neuromuscular recognition, we conducted gain-of-function
      screening for genes whose forced expression in all muscles alters the target
      specificity. We report here the identification of a novel transmembrane protein,
      Forked end (FEND), encoded by the fend gene, by the said screening. When the FEND
      expression was induced in all muscles, motoneurons that normally innervate muscle
      12 formed ectopic synapses on a neighboring muscle 13. The target specificity of
      these motoneurons was also altered in the loss-of-function mutant of fend. During
      embryonic development, fend mRNA was detected in a subset of cells in the central
      nervous system and in the periphery. These results suggest that FEND is a novel
      axon guidance molecule involved in neuromuscular specificity.

PMID- 11984843
TI  - Septum volume and food-storing behavior are related in parids.
AB  - The hippocampal formation (HF) of food-storing birds is larger than non-storing
      species, and the size of the HF in food-storing Black-Capped Chickadees (Poecile
      atricapillus) varies seasonally. We examined whether the volume of the septum, a
      medial forebrain structure that shares reciprocal connections with the HF,
      demonstrates the same species and seasonal variation as has been shown in the HF.
      We compared septum volume in three parid species; non-storing Blue Tits (Parus
      caeruleus) and Great Tits (Parus major), and food-storing Black-Capped
      Chickadees. We found the relative septum volume to be larger in chickadees than
      in the non-storing species. We also compared septum and nucleus of the diagonal
      band (NDB) volume of Black-Capped Chickadees at different times of the year. We
      found that the relative septum volume varies seasonally in food-storing birds.
      The volume of the NDB does not vary seasonally. Due to the observed species and
      seasonal variation, the septum, like the hippocampal formation of food-storing
      birds, may be specialized for some aspects of food-storing and spatial memory.

PMID- 11984844
TI  - Time course of morphological alterations of fungiform papillae and taste buds
      following chorda tympani transection in neonatal rats.
AB  - The time course of structural changes in fungiform papillae was analyzed in rats
      that received unilateral chorda tympani nerve transection at 10 days of age.
      Morphological differences between intact and denervated sides of the tongue were
      first observed at 8 days postsection, with an increase in the number of fungiform
      papillae that did not have a pore. In addition, the first papilla with a filiform
      like appearance was noted on the denervated side at 8 days postsectioning. By 11
      days after surgery, the total number of papillae and the number of papillae with
      a pore were significantly lower on the transected side of the tongue as compared
      to the intact side. At 50 days postsection, there was an average of 70.5
      fungiform papillae on the intact side and a mean of only 20.8 fungiform papillae
      the denervated side. Of those few remaining papillae on the cut side, an average
      of 13.5 papillae were categorized as filiform-like, while no filiform-like
      papillae occurred on the intact side. Significant reduction in taste bud volume
      was noted at 4 days posttransection and further decrements in taste bud volume
      were noted at 8 and 30 days postsection. Electron microscopy of the lingual
      branch of the trigeminal nerve from adult rats that received neonatal chorda
      tympani transection showed normal numbers of both myelinated and unmyelinated
      fibers. Thus, in addition to the well-characterized dependence of taste bud
      maintenance on the chorda tympani nerve, the present study shows an additional
      role of the chorda tympani nerve in papilla maintenance during early postnatal
      development.

PMID- 11984845
TI  - Multiphoton stimulation of neurons.
AB  - We pulsed the activation of neurons using a femtosecond laser. Pyramidal neurons
      are depolarized and fire action potentials when high intensity mode-locked
      infrared light irradiates somatic membranes and axon initial segments. This
      depolarization is reversible, does not occur with CW laser light, and appears to
      be due to multiphoton excitation. We describe two regimes of multiphoton optical
      stimulation. Low intensity, long duration laser irradiation produces a sustained
      depolarization, insensitive to sodium channel blockers yet sensitive to
      antioxidants. On the other hand, high intensity, short duration irradiation can
      induce fast depolarizations, which appear due to different mechanism. The
      combination of multiphoton stimulation and optical probing could enable
      systematic analysis of circuits.

PMID- 11984846
TI  - Inactivation of olfactory sensilla of a single morphological type differentially
      affects the response of Drosophila to odors.
AB  - The olfactory organs on the head of Drosophila, antennae and maxillary palps,
      contain several hundred olfactory hairs, each with one or more olfactory receptor
      neurons. Olfactory hairs belong to one of three main morphological types,
      trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial
      distribution patterns on the surface of the antenna and maxillary palps. Here we
      show that targeting expression of the cell-death gene reaper to basiconic
      sensilla (BS) causes the specific inactivation of most olfactory sensilla of this
      type with no detectable effect on other types of olfactory sensilla or the
      structure of the antennal lobe. Our data suggest that BS are required for a
      normal sensitivity to many odorants with a variety of chemical structures,
      through a wide range of concentrations. Interestingly, however, in contrast to
      other odorants tested, the behavioral response of ablated flies to intermediate
      concentrations of propionic and butyric acids is normal, suggesting the
      involvement of sensilla unaffected by ectopic reaper expression, probably
      coeloconic sensilla that respond strongly to these two organic acids. As
      inactivation of BS causes an underestimation of the concentration of both acids
      detectable at both the highest and lowest odorants concentrations, our results
      suggest that concentration coding for these two odorants relies on the
      integration of signals from different subsets of sensilla, most likely of
      different morphological types.

PMID- 11984847
TI  - Extracting hydration sites around proteins from explicit water simulations.
AB  - Two new methods are assessed for determining the location of hydration sites
      around proteins from computer simulation. Current methods extract hydration sites
      from peaks in the water density constructed in the protein frame. However, the
      dynamic nature of the water molecules, the nearby protein residues, and the
      protein reference frame as a whole tend to smear out the water density, making it
      more difficult to resolve sites. Two techniques are introduced to better resolve
      the water density. The first is to construct the water density from the time
      averaged position of each water molecule in the protein frame while the water
      remains within a given distance of this averaged position. The second technique
      is to construct the water density from the time-averaged position of each water
      in the reference frame only of the nearby residues. Criteria for determining
      hydration sites from the water density are examined. Both techniques are found to
      significantly improve the detail in the water density and the number of hydration
      sites detected.

PMID- 11984848
TI  - Quantum bits with polyacetylene.
AB  - The dynamics of a polyacetylene single chain as a system for possible physical
      implementations of quantum bits is determined. This novel proposition is studied
      by varying intensity and duration of application of an electric field as well as
      the intensity, number, and position in the polymer chain of impurity molecules.
      The behavior of soliton pairs, whose associated energy levels form the quantum
      bit, is analyzed. The chain is modeled by a modified Pariser-Parr-Pople
      Hamiltonian extended to include the effects of an external electric field and the
      parameters of the impurity molecules. The effect of the variation of the field
      and impurities on the separation of the energy levels associated with soliton
      pairs is analyzed by numerical integration of the equations of motion. Two
      different approaches for controlling the separation of levels are presented, and
      their features compared. First, the use of changes in the electric field to
      control the distance (and ultimately coupling) between two solitons moving freely
      on the chain or captured by the potential generated by the impurity molecules.
      Second, the change in the intensity of the impurities alone, with no application
      of an external field. We have found that the effect of the use of the field on
      the separation of levels is much smaller than the one obtained by changes in the
      parameters of the impurity molecules, which eventually led us to achieve quantum
      bit behavior in a polyacetylene chain. The influence of the field and impurity
      parameters in the energy levels is determined, as well as their role in the
      coupling of the two solitons on the chain. Critical values for distance between
      solitons, intensity of field, and impurities that determine whether a pair of
      solitons can work as a quantum bit are obtained.

PMID- 11984849
TI  - Theoretical investigation of electron transfer transition in tetracyanoethylene
      contained organic complexes.
AB  - In this work, the authors use complete active space self-consistent field method
      to investigate the photoinduced charge-separated states and the electron transfer
      transition in complexes ethylene-tetracyanoethylene and tetramethylethylene
      tetracyanoethylene. Geometries of isolated tetracyanoethylene, ethylene, and
      tetramethylethylene have been optimized. The ground state and the low-lying
      excited states of ethylene and tetracyanoethylene have been optimized. The state
      energies in the gas phase have been obtained and compared with the experimentally
      observed values. The torsion barrier of tetracyanoethylene has been investigated
      through the state energy calculation at different conformations. Attention has
      been particularly paid to the charge-separated states and the electron transfer
      transition of complexes. The stacked conformations of the donor-acceptor
      complexes have been chosen for the optimization of the ground and low-lying
      excited states. Equilibrium solvation has been considered by means of conductor
      like screening model both in water and in dichloromethane. It has been found that
      the donor and tetracyanoethylene remain neutral in complexes in ground state
      (1)A(1) and in lowest triplet state (3)B(1), but charge separation appears in
      excited singlet state (1)B(1). Through the correction of nonequilibrium solvation
      energy based on the spherical cavity approximation, pi-->pi* electron transfer
      transition energies have been obtained. Compared with the experimental
      measurements in dichloromethane, the theoretical results in the same solvent are
      found higher by about 0.5 eV.

PMID- 11984850
TI  - Improved RGF method to find saddle points.
AB  - The predictor-corrector method for following a reduced gradient (RGF) to
      determine saddle points [Quapp, W. et al., J Comput Chem 1998, 19, 1087] is
      further accelerated by a modification allowing an implied corrector step per
      predictor but almost without additional costs. The stability and robustness of
      the RGF method are improved, and the new version in addition reduces the number
      of gradient and Hessian calculations.

PMID- 11984851
TI  - Quantum chemical calculation of vibrational spectra of large molecules--Raman and
      IR spectra for Buckminsterfullerene.
AB  - In this work we demonstrate how different modern quantum chemical methods can be
      efficiently combined and applied for the calculation of the vibrational modes and
      spectra of large molecules. We are aiming at harmonic force fields, and infrared
      as well as Raman intensities within the double harmonic approximation, because
      consideration of higher order terms is only feasible for small molecules. In
      particular, density functional methods have evolved to a powerful quantum
      chemical tool for the determination of the electronic structure of molecules in
      the last decade. Underlying theoretical concepts for the calculation of
      intensities are reviewed, emphasizing necessary approximations and formal aspects
      of the introduced quantities, which are often not explicated in detail in
      elementary treatments of this topic. It is shown how complex quantum chemistry
      program packages can be interfaced to new programs in order to calculate IR and
      Raman spectra. The advantages of numerical differentiation of analytical
      gradients, dipole moments, and static, as well as dynamic polarizabilities, are
      pointed out. We carefully investigate the influence of the basis set size on
      polarizabilities and their spatial derivatives. This leads us to the construction
      of a hybrid basis set, which is equally well suited for the calculation of
      vibrational frequencies and Raman intensities. The efficiency is demonstrated for
      the highly symmetric C(60), for which we present the first all-electron density
      functional calculation of its Raman spectrum.

PMID- 11984852
TI  - Pure component spectral reconstruction from mixture data using SVD, global
      entropy minimization, and simulated annealing. Numerical investigations of
      admissible objective functions using a synthetic 7-species data set.
AB  - A combination of singular value decomposition, entropy minimization, and
      simulated annealing was applied to a synthetic 7-species spectroscopic data set
      with added white noise. The pure spectra were highly overlapping. Global minima
      for selected objective functions were obtained for the transformation of the
      first seven right singular vectors. Simple Shannon type entropy functions were
      used in the objective functions and realistic physical constraints were imposed
      in the penalties. It was found that good first approximations for the pure
      component spectra could be obtained without the use of any a priori information.
      The present method out performed the two widely used routines, namely Simplisma
      and OPA-ALS, as well as IPCA. These results indicate that a combination of SVD,
      entropy minimization, and simulated annealing is a potentially powerful tool for
      spectral reconstructions from large real experimental systems.

PMID- 11984853
TI  - Analytical energy gradient evaluation in relativistic and nonrelativistic density
      functional calculations.
AB  - The expressions of analytical energy gradients in density functional theory and
      their implementation in programs are reported. The evaluation of analytical
      energy gradients can be carried out in the fully 4-component relativistic,
      approximate relativistic, and nonrelativistic density functional calculations
      under local density approximation or general gradient approximation with or
      without frozen core approximation using different basis sets in our programs. The
      translational invariance condition and the fact that the one-center terms do not
      contribute to the energy gradients are utilized to improve the calculation
      accuracy and to reduce the computational effort. The calculated results of energy
      gradients and optimized geometry as well as atomization energies of some
      molecules by the analytical gradient method are in very good agreement with
      results obtained by the numerical derivative method.

PMID- 11984854
TI  - Ab initio study on the electronic structures of styrene in the Franck-Condon
      region.
AB  - The electronic structures of styrene in the Franck-Condon region have been
      theoretically examined by means of ab initio complete active space self
      consistent field (CASSCF) and the second order multireference Moller-Plesset
      calculations. The optimized structure of styrene in S(0) is planar but the
      torsional motion of the phenyl group is very floppy. The S(1) state is assigned
      to the local pi-pi* excitation within the benzene ring. On the other hand, S(2),
      above S(1) by 0.561 eV, is assigned to a state that resembles the so-called V
      state of ethylene. The transition intensity of S(0)-S(1) is weak, while that of
      S(0)-S(2) is strong. This is in good agreement with the experimental absorption
      spectrum where the S(0)-S(1) and S(0)-S(2) transitions are in the energy range of
      290-220 nm. The optimized geometry of S(1), characterized by an enlarged benzene
      ring and its vibrational analyses, further justifies the assignment of the S(1)
      state.

PMID- 11984855
TI  - Isomers of C(20): an energy profile.
AB  - Semiempirical calucaltions, at the PM 3 level, are used to geometrically optimize
      and determine the absolute energies (heats of formation) of a variety of C(20)
      isomers. Based on the geometrically optimized Cartesian coordinates of the ring
      and the bowl isomers, and the subsequent saddle-point calculation, a two
      dimensional energy profile between these two isomers is generated. Performing
      geometry optimization on the Cartesian coordinates that correspond to energy
      minima within the ring-bowl profile, we have been able to identify several more
      isomers of C(20) that are predicted to be energitically stable. With these
      additional stable structures, we have identified pairs of isomers that lie
      adjacent to one another on the potential energy surface, as is evidenced by the
      form of their respective energy profiles. These adjacent pairs of isomers
      establish a step-wise transformation between the ring and the bowl. This process,
      which extends out over the three-dimensional surface, is predicted to require
      less energy than that of the direct, two-dimensional transformation predicted in
      the ring-bowl profile.

PMID- 11984856
TI  - Measurement of dopamine transporter occupancy for multiple injections of cocaine
      using a single injection of [F-18]FECNT.
AB  - The fraction of transporters occupied following injection of specific inhibitors
      is an important parameter for defining and comparing the molecular mechanisms of
      different drugs. This work generalizes the reference tissue method to estimate
      dopamine transporter occupancy for two levels of cocaine administration using
      only a single injection of [(18)F]FECNT. The results are validated by comparison
      with literature values. Five rhesus monkeys were studied. On each animal, a
      baseline scan was collected following [(18)F]FECNT injection (phase a). At 120
      min postinjection, 0.1 mg/kg cocaine was injected and the animal was scanned for
      50 additional min (phase b). Then 1.0 mg/kg cocaine was injected and another 50
      min scan sequence was collected (phase c). Time-activity curves (encompassing all
      three phases) were generated for each animal from regions drawn over the putamen
      and cerebellum. The putamen curve was modeled using the cerebellum as the input
      function. Percent DAT occupancy following the cocaine injections was determined
      by comparing k(3)/k(4) = B(max)/k(D) for the three phases. The 0.1 and 1.0 mg/kg
      cocaine doses occupied 53% +/- 5% and 87% +/- 5% of the transporters,
      respectively. The measured occupancies are consistent with literature values that
      maintain self-administration in animals and produce a "high" in human subjects.
      This work demonstrates that a single injection of [(18)F]FECNT can be used to
      measure the effects of multiple cocaine challenges. Two advantages of this
      technique are: reduced variability in dose-response curves because the subject is
      his/her own control, and the (18)F label allows evaluation of longer-acting
      drugs.

PMID- 11984857
TI  - Distinct gene expression signatures in the striata of wild-type and heterozygous
      c-fos knockout mice following methamphetamine administration: evidence from cDNA
      array analyses.
AB  - Methamphetamine (METH) is a drug of abuse which can cause apoptosis and
      degeneration of monoaminergic terminals in the mammalian brain. c-fos appears to
      play a protective role against METH-induced damage because METH toxicity is
      exacerbated in c-fos heterozygous knockout mice. In the present study, we used
      the comprehensive technique of cDNA array to test the idea that heterozygous c
      fos knockout mice might show differential METH-induced molecular responses in
      comparison to wild-type (WT) animals. Of 1,176 genes examined, the expression of
      195 genes in either of the two groups of mice was affected by at least 2-fold at
      2 or 12 h after METH treatment. More genes were either up- or downregulated in
      the WT mice. Moreover, there were substantial differences in the pattern of
      responses between the two genotypes, with more genes involved in DNA repair and
      protective processes being upregulated in WT mice after METH administration.
      These results support the idea that the c-fos knockout genotype may render the
      animals unable to trigger multicomponent responses in order to protect against
      the multifaceted toxic effects of this illicit neurotoxin.

PMID- 11984858
TI  - Regulation of striatal dopamine neurotransmission by nitric oxide: effector
      pathways and signaling mechanisms.
AB  - An important role for the reactive gas nitric oxide (NO) in regulating striatal
      dopaminergic neurotransmission was identified shortly after initial observations
      indicated that this unorthodox neurotransmitter mediates many of the influences
      of glutamatergic neurotransmission in the cerebellum, cortex, and hippocampus.
      While the precise actions of NO on striatal presynaptic and postsynaptic elements
      remain to be fully characterized, the recent application of sophisticated
      anatomical, neurochemical, and electrophysiological approaches to the study of
      nitrergic signaling has revealed that NO exerts a powerful influence both on
      tonic extracellular dopamine (DA) levels and phasic DA neuron spike activity via
      the modulation of intrinsic striatal mechanisms and striatonigral feedback loops.
      Although the nature of the NO-mediated modulatory influence on DA
      neurotransmission was initially clouded by seemingly conflicting neurochemical
      observations, a growing body of literature and understanding of the diverse
      signaling mechanisms and effector pathways utilized by NO indicates that NO
      exerts a primary facilitatory influence over tonic and phasic dopaminergic
      neurotransmission under physiological conditions. A review of neurochemical and
      electrophysiological studies examining the influence of endogenous and exogenous
      NO on DA neurotransmission indicates that NO signaling exerts multiple effects on
      local striatal circuits and projection neurons involved in regulating basal
      ganglia output and nigrostriatal DA neuron activity. In addition to summarizing
      these influences, the current review focuses on the mechanisms utilized by
      striatal NO signaling pathways involved in modulating DA transmission at the
      level of the terminal and cell body and attempts to integrate these observations
      into a functional model of NO-dependent regulation of basal ganglia systems.

PMID- 11984859
TI  - Effect of tetrabenazine on the striatal uptake of exogenous L-DOPA in vivo: a PET
      study in young and aged rhesus monkeys.
AB  - The effect of tetrabenazine (TBZ) pretreatment on the striatal uptake of
      exogenous L-DOPA in vivo was assessed noninvasively in rhesus monkeys by positron
      emission tomography (PET) using the tracer [(18)F]-FluoroDOPA (FDOPA). Paired
      studies were done comparing baseline vs. TBZ treatment on the uptake of FDOPA, a
      measure of aromatic L-amino acid decarboxylase (AAAD) activity. Results show
      increased AAAD activity with TBZ treatment. These results suggest that the action
      of TBZ as a dopamine antagonist dominates more than its expected action as a
      potent vesicular monoamine transporter (VMAT2) inhibitor. Results also showed
      diminished responsivity of AAAD to TBZ challenge in aged monkey brain.

PMID- 11984860
TI  - Increased GABA neurotransmission via administration of gamma-vinyl GABA decreased
      nicotine self-administration in the rat.

PMID- 11984862
TI  - Interactions between genetic and reproductive factors in breast cancer risk in a
      population-based sample of African-American families.
AB  - Incidence of breast cancer (BC) varies among ethnic groups, with higher rates in
      white than in African-American women. Until now, most epidemiological and genetic
      studies have been carried out in white women. To investigate whether interactions
      between genetic and reproductive risk factors may explain part of the ethnic
      disparity in BC incidence, a genetic epidemiology study was conducted, between
      1989 and 1994, at the Howard University Cancer Center (Washington, DC), which led
      to the recruitment of 245 African-American families. Segregation analysis of BC
      was performed by use of the class D regressive logistic model that allows for
      censored data to account for a variable age of onset of disease, as implemented
      in the REGRESS program. Segregation analysis of BC was consistent with a putative
      dominant gene effect (P < 0.000001) and residual sister-dependence (P < 0.0001).
      This putative gene was found to interact significantly with age at menarche (P =
      0.048), and an interaction with a history of spontaneous abortions was suggested
      (P = 0.08). A late age at menarche increased BC risk in gene carriers but had a
      protective effect in non-gene carriers. A history of spontaneous abortions had a
      protective effect in gene carriers and increased BC risk in non-gene carriers.
      Our findings agree partially with a similar analysis of French families showing a
      significant gene x parity interaction and a suggestive gene x age at menarche
      interaction. Investigating gene x risk factor interactions in different
      populations may have important implications for further biological investigations
      and for BC risk assessment.

PMID- 11984863
TI  - Unified sampling approach for multipoint linkage disequilibrium mapping of
      qualitative and quantitative traits.
AB  - Rapid development in biotechnology has enhanced the opportunity to deal with
      multipoint gene mapping for complex diseases, and association studies using
      quantitative traits have recently generated much attention. Unlike the
      conventional hypothesis-testing approach for fine mapping, we propose a unified
      multipoint method to localize a gene controlling a quantitative trait. We first
      calculate the sample size needed to detect linkage and linkage disequilibrium
      (LD) for a quantitative trait, categorized by decile, under three different modes
      of inheritance. Our results show that sampling trios of offspring and their
      parents from either extremely low (EL) or extremely high (EH) probands provides
      greater statistical power than sampling in the intermediate range. We next
      propose a unified sampling approach for multipoint LD mapping, where the goal is
      to estimate the map position (tau) of a trait locus and to calculate a confidence
      interval along with its sampling uncertainty. Our method builds upon a model for
      an expected preferential transmission statistic at an arbitrary locus conditional
      on the sampling scheme, such as sampling from EL and EH probands. This approach
      is valid regardless of the underlying genetic model. The one major assumption for
      this model is that no more than one quantitative trait locus (QTL) is linked to
      the region being mapped. Finally we illustrate the proposed method using family
      data on total serum IgE levels collected in multiplex asthmatic families from
      Barbados. An unobserved QTL appears to be located at tau; = 41.93 cM with 95%
      confidence interval of (40.84, 43.02) through the 20-cM region framed by markers
      D12S1052 and D12S1064 on chromosome 12. The test statistic shows strong evidence
      of linkage and LD (chi-square statistic = 18.39 with 2 df, P-value = 0.0001).

PMID- 11984864
TI  - Mapping multiple genes for quantitative or complex traits.
AB  - Models for complex and quantitative traits that involve multiple, possibly
      interacting, genes are described. Methods of linkage analysis are developed that
      utilize special features of these models, and their power is compared with that
      of simple genome scans that ignore these special features. Our calculations show
      that for family-based nonparametric linkage analysis in human genetics, in
      contrast to experimental genetics, there are limits to the increase in power that
      can be achieved by correctly modeling gene-gene interactions. In particular, the
      noncentrality parameter of likelihood-based statistics to detect single gene
      effects involves both single gene and interaction components of variance, so even
      when the interaction components of variance are relatively large, the incremental
      power from a statistic designed to detect both single gene and interaction
      effects is often quite modest. We carry out our analysis with the assistance of a
      parameterization that allows us to compute score statistics, noncentrality
      parameters, and Fisher information matrices reasonably explicitly.

PMID- 11984865
TI  - Allele sharing and allelic association I: sib pair tests with increased power.
AB  - Affected sib pair data contain information about allele sharing and allelic
      association. Either of these features can point to the presence of a risk-related
      gene. This study introduces the elliptical sib pair test, a generalization of
      traditional sib pair tests. The proposed test can be implemented using any of
      three strategies, the choice of which depends on the anticipated combination of
      sharing and association. The elliptical sib pair test can achieve substantial
      gains in power relative to traditional tests for likely alternative hypotheses at
      little or no cost for other alternatives. The proposed test is valid under most
      models of genetic risk, disease etiology, and genotype-haplotype distributions.
      This study also provides new insight into the trade-off between tests of allelic
      association and tests of allele sharing.

PMID- 11984866
TI  - Score test for detecting linkage to quantitative traits.
AB  - The two most popular methods to detect linkage of a quantitative trait to a
      marker are the Haseman-Elston regression method and the variance components
      likelihood-ratio test. In the literature, these methods are frequently compared
      and the relative advantages and disadvantages of each method are well known. In
      this article, we derive a score test for the variance component attributable to a
      specific quantitative trait locus and show that for sib-pairs it is
      mathematically equivalent to a recently proposed version of the Haseman-Elston
      method that optimally combines the sum squared and the difference squared of the
      centered phenotype values of the sibs. Because score tests and likelihood-ratio
      tetsts are equivalent for large sample sizes, the variance components likelihood
      ratio test is also asymptotically equivalent to this optimal Haseman-Elston test.
      This fact gives a theoretical explanation of the empirical observation from
      simulation studies reporting similar power of the variance components likelihood
      ratio test and the optimal Haseman-Elston method. Perhaps more importantly for
      practical purposes, the score test can also be extended in a natural way to
      support the simultaneous analysis of more than two subjects and multivariate
      phenotypes.

PMID- 11984867
TI  - A Bayesian partition model for case-control studies on highly polymorphic
      candidate genes.
AB  - We present a new statistical model for the analysis of case-control or cohort
      studies examining a highly polymorphic candidate disease susceptibility gene.
      Many genotypes are possible for such a gene. Consequently, the average number of
      subjects having each genotype will be modest. If analyzed separately, the risks
      associated with most genotypes will be estimated imprecisely. Our Bayesian
      partition model clusters genotypes according to risk, only allowing partitions
      that satisfy a particular assumption about the joint effect of the two alleles
      making up a genotype. This assumption is genetically plausible, imposes structure
      on the set of genotype risks, and still leaves a highly flexible model. By
      Bayesian model averaging over partitions, the model becomes, in effect, a
      semiparametric model for genotype risk. It allows borrowing of strength, i.e.,
      estimates of risk for one genotype are informed by the risk estimates of all the
      genotypes. We present the results of fitting the model to two datasets, one
      simulated and one genuine case-control study of the NAT1 gene and lung cancer,
      and compare it in a simulation study with a haplotype relative risk model. The
      partition model enables genotype risks to be estimated more accurately and the
      alleles to be ranked according to risk.

PMID- 11984868
TI  - A note on estimating the posterior density of a quantitative trait locus from a
      Markov chain Monte Carlo sample.
AB  - We provide an overview of the use of kernel smoothing to summarize the
      quantitative trait locus posterior distribution from a Markov chain Monte Carlo
      sample. More traditional distributional summary statistics based on the histogram
      depend both on the bin width and on the sideway shift of the bin grid used. These
      factors influence both the overall mapping accuracy and the estimated location of
      the mode of the distribution. Replacing the histogram by kernel smoothing helps
      to alleviate these problems. Using simulated data, we performed numerical
      comparisons between the two approaches. The results clearly illustrate the
      superiority of the kernel method. The kernel approach is particularly efficient
      when one needs to point out the best putative quantitative trait locus position
      on the marker map. In such situations, the smoothness of the posterior estimate
      is especially important because rough posterior estimates easily produce biased
      mode estimates. Different kernel implementations are available from Rolf
      Nevanlinna Institute's web page (http://www.rni.helsinki.fi/;fjh).

PMID- 11984869
TI  - Constructing the hindbrain: insights from the zebrafish.
AB  - The hindbrain is responsible for controlling essential functions such as
      respiration and heart beat that we literally do not think about most of the time.
      In addition, cranial nerves projecting from the hindbrain control muscles in the
      jaw, eye, and face, and receive sensory input from these same areas. In all
      vertebrates that have been studied, the hindbrain passes through a segmented
      phase shortly after the neural tube has formed, with a series of seven bulges-
      the rhombomeres--forming along the anterior-posterior extent of the neural tube.
      Our current understanding of vertebrate hindbrain development comes from
      integrating data from several model systems. Work on the chick has helped us to
      understand the cell biology of the rhombomeres, whereas the power of mouse
      molecular genetics has allowed investigation of the molecular mechanisms
      underlying their development. This review focuses on the special insights that
      the zebrafish system has provided to our understanding of hindbrain development.
      As we will discuss, work in the zebrafish has elucidated inductive events that
      specify the presumptive hindbrain domain and has identified genes required for
      hindbrain segmentation and the specification of segment identities.

PMID- 11984870
TI  - Turn-off, drop-out: functional state switching of cadherins.
AB  - The classic cadherins are a group of calcium dependent, homophilic cell-cell
      adhesion molecules that drive morphogenetic rearrangements and maintain the
      integrity of cell groups through the formation of adherens junctions. The
      formation and maintenance of cadherin-mediated adhesions is a multistep process
      and mechanisms have evolved to regulate each step. This suggests that functional
      state switching plays an important role in development. Among the many challenges
      ahead is to determine the developmental role that functional state switching
      plays in tissue morphogenesis and to define the roles of each of the several
      regulatory interactions that participate in switching. One correlate of the loss
      of cadherin-mediated adhesion, the "turn-off" of cadherin function, is the exit,
      or "drop-out" of cells from neural and epithelial layers and their conversion to
      a motile phenotype. We suggest that epithelial mesenchymal conversions may be
      initiated by signaling pathways that result in the loss of cadherin function.
      Tyrosine phosphorylation of beta-catenin is one such mechanism. Enhanced
      phosphorylation of tyrosine residues on beta-catenin is almost invariably
      associated with loss of the cadherin-actin connection concomitant with loss of
      adhesive function. There are several tyrosine kinases and phosphatases that have
      been shown to have the potential to alter the phosphorylation state of beta
      catenin and thus the function of cadherins. Our laboratory has focused on the
      role of the nonreceptor tyrosine phosphatase PTP1B in regulating the
      phosphorylation of beta-catenin on tyrosine residues. Our data suggest that PTP1B
      is crucial for maintenance of N-cadherin-mediated adhesions in embryonic neural
      retina cells. By using an L-cell model system constitutively expressing N
      cadherin, we have worked out many of the molecular interactions essential for
      this regulatory interaction. Extracellular cues that bias this critical
      regulatory interaction toward increased phosphorylation of beta-catenin may be a
      critical component of many developmental events.

PMID- 11984871
TI  - Mouse dystrophin enhancer preferentially targets lacZ expression in skeletal and
      cardiac muscle.
AB  - Duchenne muscular dystrophy is a muscle wasting disease that results from a
      dystrophin deficiency in skeletal and cardiac muscle. Studies concerning the
      regulatory elements that govern dystrophin gene expression in skeletal and/or
      cardiac muscle in both mouse and human have identified a promoter and an enhancer
      located in intron 1. In transgenic mice, the muscle promoter alone targets the
      expression of a lacZ reporter gene only to the right ventricle of the heart,
      suggesting the need for other regulatory elements to target skeletal muscle and
      the rest of the heart. Here we report that the mouse dystrophin enhancer from
      intron 1 can target the expression of a lacZ reporter gene in skeletal muscle as
      well as in other heart compartments of transgenic mice. Our results also suggest
      that sequences surrounding the mouse dystrophin enhancer may affect its function
      throughout mouse development.

PMID- 11984872
TI  - Ontogenesis of female-to-male sex-reversal in XX polled goats.
AB  - The association of polledness and intersexuality in domestic goats (PIS mutation)
      made them a practical genetic model for studying mammalian female-to-male sex
      reversal. In this study, gonads from XX sex-reversed goats (PIS-/-) were
      thoroughly characterized at the molecular and histologic level from the first
      steps of gonadal differentiation (36 days post coitum [dpc]) to birth. The first
      histologic signs of gonadal sex reversal were detectable between 36 and 40 dpc (4
      5 days later than the XY male) and were mainly characterized by the reduction of
      the ovarian cortex and the organization of seminiferous cords. As early as 36
      dpc, aromatase (CYP19) gene expression was decreased in XX (PIS-/-) gonads,
      whereas genes normally up-regulated in males, such as SOX9 and AMH, showed an
      increased expression level from 40 dpc. Thereafter, steroidogenic cell precursors
      were affected, and at 56 dpc, WNT4 and 3beta-HSD were expressed in a male
      specific manner in sex-reversed gonads. Another noticeable feature was a
      progressive disappearance of germ cells, clearly visible in testicular cords
      around 70 dpc where 50-75% of germ cells were absent in XX (PIS-/-) gonads. These
      observations indicated that the causal mutation of PIS acts very early in the sex
      determining cascade and affects primarily the supporting cells of the gonad.

PMID- 11984873
TI  - Evidence for a glycosaminoglycan on the nudel protein important for dorsoventral
      patterning of the drosophila embryo.
AB  - Dorsoventral patterning of the Drosophila embryo requires Nudel, a large mosaic
      protein with a protease domain. Previous studies have implicated Nudel's protease
      domain as the trigger of a proteolytic cascade that activates the Toll signaling
      pathway to establish dorsoventral polarity in the embryo. However, the function
      of other regions of Nudel has been unclear. By using two-dimensional gel
      electrophoresis and site-directed mutagenesis, we have obtained evidence that the
      N-terminal region of Nudel contains a site for glycosaminoglycan (GAG) attachment
      that is required for dorsoventral patterning. Disruption of this site blocks a
      disulfide-based association between N- and C-terminal Nudel polypeptides and
      proteolytic activation of Nudel's protease domain. We discuss how a GAG chain on
      Nudel might be required for Nudel protease activation.

PMID- 11984874
TI  - HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders
      and modulates keratinocyte proliferation.
AB  - The HOX homeodomain proteins are fundamental regulators of organ and tissue
      development, where they are thought to function as transcription factors, and HOX
      gene expression has been associated with numerous types of cancers. Previous
      studies have demonstrated that enforced expression of the HOXB4 protein
      transforms cultured fibroblasts and leads to a selective expansion of the
      hematopoietic stem cell pool, suggesting that this protein might play a role in
      cellular proliferation. In support of this concept, we now show that enforced
      expression of HOXB4 in human neonatal keratinocytes results in increased cellular
      proliferation and colony formation as well as decreased expression of the alpha-2
      integrin and CD44 cell surface adhesion molecules. We previously have reported
      HOXB4 gene expression in the basal and suprabasal layers of developing human skin
      and now show extensive HOXB4 mRNA in psoriatic skin and basal cell carcinoma. In
      fetal human skin HOXB4 protein expression was both nuclear and cytoplasmic within
      epidermal basal cells and in hair follicle inner and outer root sheath cells,
      whereas strong nuclear signals were observed in the bulge region. In adult skin,
      HOXB4 protein expression was both nuclear and cytoplasmic, but was predominantly
      localized to the intermediate and differentiated cell layers. In contrast to the
      striking gradient patterns of HOX gene and protein expression previously
      described in developing spinal cord and limb, HOXB4 protein was uniformly
      detected in all regions of the fetal and adult skin. Although little HOXB4 signal
      localized to proliferative cell layers, as marked by proliferating cell nuclear
      antigen (PCNA) staining, in normal adult epidermis, nuclear HOXB4 protein
      expression substantially overlapped with PCNA-positive cell in a series of
      samples of hyperproliferative skin. Taken together, these data suggest that
      nuclear HOXB4 protein may play a role in the regulation of cellular
      proliferation/adhesion in developing fetal human epidermis and in
      hyperproliferation conditions, including cancers, in adult epidermis. Published
      2002 Wiley-Liss, Inc.

PMID- 11984875
TI  - Receptor-regulated and inhibitory Smads are critical in regulating transforming
      growth factor beta-mediated Meckel's cartilage development.
AB  - The proper development of Meckel's cartilage is critical for craniofacial
      skeletogenesis, because it serves as the primordium for the formation of
      mandible, malleus, incus, and sphenomandibular ligament. Cranial neural crest
      (CNC) cells contribute significantly to the formation of Meckel's cartilage.
      Members of the transforming growth factor beta (TGF-beta) family control the
      proliferation and differentiation of CNC cells during craniofacial
      skeletogenesis. TGF-beta signaling is transduced from the cell membrane to the
      nucleus by means of specific type I and type II receptors and phosphorylated Smad
      proteins. Here we demonstrate that application of TGF-beta promotes
      chondrogenesis by specifically increasing proliferation of CNC-derived
      chondrocytes and production of extracellular matrix. To understand the molecular
      regulation of TGF-beta signaling, we have examined the biological function of
      both TGF-beta receptor-regulated and inhibitory Smads during Meckel's cartilage
      development. The expression patterns of Smad2, 3, and 7 are identical to the ones
      of endogenous TGF-beta and its cognate receptors during Meckel's cartilage
      development, establishing the potential that these intracellular signaling Smads
      may regulate TGF-beta-mediated chondrogenesis. Functional haploinsufficiency of
      Smad2 delays TGF-beta-mediated Meckel's cartilage development. Overproduction of
      Smad7 severely inhibits Meckel's cartilage formation, indicating a negative
      feedback on TGF-beta signaling by inhibitory Smad is critical in orchestrating
      TGF-beta-mediated gene regulation during embryonic chondrogenesis. The
      effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene
      expression.

PMID- 11984876
TI  - Growth defect in Grg5 null mice is associated with reduced Ihh signaling in
      growth plates.
AB  - Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro),
      results in postnatal growth retardation in mice. The growth defect, most striking
      in approximately half of the Grg5 null mice, occurs during the first 4-5 weeks of
      age, but most mice recover retarded growth later. We used the nonlinear mixed
      effects model to fit the growth data of wild-type, heterozygous, and Grg5 null
      mice. On the basis of preliminary evidence suggesting an interaction between Grg5
      and the transcription factor Cbfa1/Runx2, critical for skeletal development, we
      further investigated the skeleton in the mice. A long bone growth plate defect
      was identified, which included shorter zones of proliferative and hypertrophic
      chondrocytes and decreased trabecular bone formation. This decreased trabecular
      bone formation is likely caused by a reduced recruitment of osteoblasts into the
      growth plate region of Grg5 null mice. Like the growth defect, the growth plate
      and trabecular bone abnormality improved as the mice grew older. The growth plate
      defect was associated with reduced Indian hedgehog expression and signaling. We
      suggest that Grg5, a transcriptional coregulator, modulates the activities of
      transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and
      the function of long bone growth plates.

PMID- 11984877
TI  - Villin: A marker for development of the epithelial pyloric border.
AB  - In the adult gastrointestinal tract, the morphologic borders between esophagus
      and stomach and between stomach and small intestine are literally one cell thick.
      The patterning mechanisms that underlie the development of these sharp regional
      divisions from a once continuous endodermal tube are still obscure. In the
      embryonic endoderm of the developing gut, region-specific expression of certain
      genes (e.g., intestine-specific expression of the actin bundling protein villin)
      can be detected as early as 9.0 days post coitum, although the morphologic
      differentiation of the gut epithelium proper does not begin until 4 to 5 days
      later. By using a mouse model in which a beta-galactosidase marker has been
      inserted into the endogenous villin locus, we examined the development of the
      stomach/intestinal (pyloric) border during gut organogenesis. The data indicate
      that the border is not sharp from the outset. Rather, the initial border region
      is characterized by a decreasing gradient of villin/beta-galactosidase expression
      that extends into the distal stomach. A sharp epithelial border of villin/beta
      galactosidase expression appears abruptly at day 16 and is further refined over
      the next 3 weeks to form the distinct one-cell-thick border characteristic of the
      adult. These results indicate that an important previously unrecognized
      patterning event occurs in the gut epithelium at 16 days; this event may define
      an epithelial compartment boundary between the stomach and the intestine. The
      villin/beta-galactosidase mouse model characterized here provides an excellent
      substrate with which to further dissect the mechanisms involved in this
      patterning process.

PMID- 11984878
TI  - Multistep role for actin in initial closure of the mesencephalic neural groove in
      the chick embryo.
AB  - In a previous study, we have demonstrated that initial closure of the
      mesencephalic neural groove in the chick embryo is different from neurulation
      elsewhere. The neural groove invaginates, the walls appose and make contact in a
      ventrodorsal direction, and subsequently separate ventrally, forming an incipient
      neural tube lumen, which finally widens into a definitive lumen. In this study, a
      role for actin in the processes of this initial mesencephalic closure is studied.
      Based on rhodamine-phalloidin-stained sections, three distinct actin distribution
      patterns emerged, and time-lapse video microscopy revealed cytochalasin-D
      reversible neurulation movements. We propose that actin is involved in formation
      and stabilization of the neural groove hinge point, in invagination of dorsal
      neuroepithelial cells into the neural groove, in the origin of the incipient
      lumen and the reinforcement of adhesion of the dorsal neural folds, and finally
      in the development of a wide lumen. Such a multifunctional effect of actin
      microfilaments within a narrow time window and at specific sites has not been
      reported yet.

PMID- 11984879
TI  - Cloning and expression analysis of the chick DAN gene, an antagonist of the BMP
      family of growth factors.
AB  - Differential screening-selected gene aberrative in neuroblastoma (DAN) is a
      member of a cystine knot protein family that includes Cerberus and Gremlin. First
      isolated in a screen to identify genes down-regulated in transformed rat
      fibroblasts, DAN has subsequently been cloned in Xenopus, mouse, and human.
      Overexpression of DAN suppresses the transformed phenotype and retards the cell's
      entry into S phase. Biochemical analyses have demonstrated DAN's ability to bind
      bone morphogenetic proteins and antagonize their signaling activity. In this
      study, chick DAN was cloned and sequenced, revealing a conserved cystine knot
      region as well as an N-glycosylation site. A riboprobe was designed from the 3'
      chick DAN coding sequence and used for analysis of DAN in the developing chick
      embryo by in situ hybridization. Chick DAN was expressed beginning at stage 10 in
      the developing somites and the medial otic epithelium. Expression in the neural
      layer of the eye became apparent at stage 14. By stage 17, expression had
      expanded to the base of the hindbrain. Limb bud labeling began at stage 20,
      whereas expression in the branchial arches appeared at stage 25. Chick DAN
      expression generally corresponded to that of mouse DAN expression as shown by
      comparative in situ hybridization. However, chick DAN was found in the otic
      epithelium and notochord, whereas mouse DAN was restricted to the overlying otic
      ectomesenchyme and was absent from the notochord. This observation suggests that
      DAN may play different roles in chick and mouse otic and notochord development.

PMID- 11984880
TI  - Isolation of DNTNP, which encodes a potential nuclear protein that is expressed
      in the developing, dorsal neural tube.
AB  - We have performed a screen to identify genes expressed in a functionally
      significant anatomic region of the vertebrate dorsal neural tube, the dorsomedial
      roof of the third ventricle (DMRTV). The DMRTV includes the primordia of a series
      of circumventricular organs. The screen searched for genes preferentially
      expressed in the DMRTV of stage 18-25 chicken embryos, relative to their
      telencephala and ventral diencephalon. Through this screen, we have cloned a
      series of genes strongly expressed in the dorsal but not ventral neural tube. We
      describe here the first of these genes, DNTNP (dorsal neural tube nuclear
      protein). DNTNP is highly expressed in the dorsal regions of the diencephalon,
      the midbrain, the hindbrain, and the spinal neural tube in the chicken stage 18
      embryo. Expression is also observed in the telencephalon, the branchial arches,
      the heart, and somites, but is absent from the presomitic mesoderm. The amino
      acid sequence of DNTNP reveals that it belongs to an uncharacterized protein
      family with at least two additional members. All the members of this family
      possess a basic region reminiscent of a nuclear localization signal (NLS). We
      demonstrate that the putative NLS of DNTNP can indeed direct nuclear localization
      of green fluorescent protein (GFP). The dorsal localization of DNTNP in the early
      embryonic central nervous system suggests roles for this molecule in specifying
      dorsal cell fates within the neural tube.

PMID- 11984886
TI  - How to build a birth network.

PMID- 11984887
TI  - Midwifery Arts Center. Establishing our vision.

PMID- 11984888
TI  - A circle of women. Building a freestanding birth center.

PMID- 11984889
TI  - Unexpected allies. How a rural hospital medical staff came to the support of
      midwives.

PMID- 11984890
TI  - Where is your birth community?

PMID- 11984891
TI  - Interconnections. Faith, love, beauty and birth.

PMID- 11984892
TI  - The blessings of a birthing community.

PMID- 11984893
TI  - Life is not a tame lion. A response to the Midwifery Today Issue 56 editorial.

PMID- 11984894
TI  - Warrior midwife.

PMID- 11984895
TI  - Becoming a holistic traditional midwife.

PMID- 11984896
TI  - Regulating midwifery. Parallels in Texas and British Columbia.

PMID- 11984897
TI  - Traditional midwifery in danger.

PMID- 11984898
TI  - Lessons. What a midwife imparts to her daughter.

PMID- 11984899
TI  - Honoring traditional midwifery apprentices--my daughters!

PMID- 11984900
TI  - Vitamin K deficiency. The waterbirth and hospitalization of Amanda.

PMID- 11984901
TI  - Vitamin K: a flaw in the blueprint?

PMID- 11984902
TI  - Babies and vitamin K.

PMID- 11984903
TI  - Risk assessment and the new World Health Organization recommendations.

PMID- 11984904
TI  - Essential oils and miscarriage.

PMID- 11984905
TI  - Challenges facing midwives on both sides of the Atlantic.

PMID- 11984906
TI  - Observing and charting for family planning.

PMID- 11984907
TI  - The ripe pomegranate. Choosing in vitro fertilization.

PMID- 11984908
TI  - Guatemala journey. Partnering with traditional midwives.

PMID- 11984909
TI  - Global midwifery: topic group report. Midwifery Today's New York City
      International Conference, September 2000.

PMID- 11984910
TI  - Water stillbirth.

PMID- 11984911
TI  - More on Rhogam.

PMID- 11984912
TI  - Make room at the table. Building and sustaining a strong birth community.

PMID- 11984913
TI  - PPS: the supply issue.

PMID- 11984914
TI  - TPN update: making each visit count.
AB  - Caring for patients on TPN is a challenge for the home care nurse. These patients
      may present with either a short- or long-term need for TPN but in either case,
      the impact on daily life related to administration and monitoring of this complex
      infusion therapy is significant for both patients and their caregivers. The risks
      and complications of TPN can be serious. Nurses must possess expert knowledge of
      TPN administration and a high level of competence in assessment and monitoring of
      patients on TPN. Patients and caregivers will learn technical procedures in the
      home that produce anxiety in graduate nurses! The nurse must also possess skill
      and confidence in teaching patients to effectively administer, manage, and
      incorporate TPN infusion therapy into their lives.

PMID- 11984915
TI  - Why caregiver depression, and self-care abilities should be part of the PPS case
      mix methodology. Interview by Robert Ferry.

PMID- 11984916
TI  - Avoiding the pitfalls of hospice continuous care.

PMID- 11984917
TI  - Ensuring the quality of OASIS data: one agency's plan.

PMID- 11984918
TI  - How to develop a written progress report following a Joint Commission home care
      survey.

PMID- 11984919
TI  - ACE inhibitors.

PMID- 11984920
TI  - What you need to know about dietary supplements.
AB  - Herbs and botanicals are used by a large number of people in the United States
      and have been used therapeutically in Europe for decades. Consumers are becoming
      more interested and subsequently better informed on the use of herbs to self
      treat minor illness. Unfortunately, because of conflicting and anecdotal
      information, variable potency, and the widespread availability of herbs, many
      home care patients are left vulnerable to potentially life-threatening
      situations. A neutral discussion of alternative medical treatment should occur
      with all home care patients. Carefully worded questions should be asked and
      documented in the medical record. Finally, science-based teaching tools outlining
      the risks and benefits of botanicals must be available. A registered dietitian or
      pharmacist should be able to help nurses and agencies locate appropriate teaching
      tools on dietary supplements, including commonly used herbs and meal
      replacements.

PMID- 11984921
TI  - HPNA monographs foster quality care.

PMID- 11984922
TI  - Rural and urban nurses are on common ground.

PMID- 11984923
TI  - HHNA's core curriculum.

PMID- 11984924
TI  - Three patients' tele-home care experiences.

PMID- 11984925
TI  - Referral rate to transplant higher for whites than blacks.

PMID- 11984926
TI  - Proposal by Fresenius Medical Care to fold in separately billable laboratory
      tests.

PMID- 11984927
TI  - Medical psychologists in the past several months who are advocating for
      psychological services for end-stage renal disease (ESRD) patients.

PMID- 11984928
TI  - Amgen asks judge for speedy ruling in patent case.

PMID- 11984929
TI  - Daily dialysis and long-term outcomes--the Lynchburg Nephrology NHHD experience.

PMID- 11984930
TI  - Composite rate increase, improved drug coverage are bright spots in a tough year
      of investigations, legal battles, and provider miscues.

PMID- 11984931
TI  - Political turmoil in organ allocation.

PMID- 11984932
TI  - RPA an advocate for excellence in nephrology in 1999.

PMID- 11984933
TI  - NKF continues Making Lives Better, promotes rehabilitation in 1999.

PMID- 11984934
TI  - [Severe sepsis and septic shock].

PMID- 11984935
TI  - [Prophylaxis against opportunistic microorganisms].

PMID- 11984936
TI  - [Clinical profile of infections caused by opportunistic microorganisms in HIV
      positive patients--own observation].

PMID- 11984937
TI  - [Tuberculosis and mycobacteriosis important opportunistic disease in AIDS
      patients].
AB  - OBJECTIVE: The aim of the search was investigation of tuberculosis in AIDS
      patients. Each year 8-9 mln people fall ill of tuberculosis and one third of them
      die. To the infection of tuberculosis and fast development into active state are
      especially exposed people with AIDS. MATERIAL AND METHODS: 696 people were
      examined on tuberculosis most of which were AIDS patients hospitalized and cured
      in Hospital of Infection Diseases and Prison Hospital. 159 patients were women
      and 537 were men. The average age was between 25 and 45 (70%). The investigated
      population was characterized according to age, social and living conditions,
      using drugs and former contact with tuberculosis. All patients suspected of
      tuberculosis had chest X-rayed, sputum, BAL and pleural liquor were taken to
      bacteriological examination when extrapulmonary tuberculosis was suspected. The
      material was taken adequately to the disease process: CSF, urine, lymph nodes,
      peritoneal fluids, blood, stool, swabs and other. Bacteriological investigations
      have been carried out by fast cultivating method since 1998 and rapid genetic
      method since 1999. Apart from modern, fast diagnostic methods, routine
      bacteriological procedures were applied in tuberculosis diagnosis. RESULTS: More
      than 30% of the examined population were from bad social-living conditions, 78%
      had risk factors, 65% were drug users. The analysis of the tuberculosis illness
      from 1997 to July 2001 shows growing tendency. Nowadays it is 20% cases proved by
      bacteriological diagnosis. The structure of falling ill with tuberculosis has
      changed. Considerable increase of extrapulmonary tuberculosis was observed, 20
      patients died due to tuberculosis and 8 patients due to mycobacteriosis.
      Resistance of M.tub.complex occurred within the range of 10% cases.

PMID- 11984938
TI  - [Opportunistic infections in HIV-positive patients hospitalized in the Clinic of
      Infectious Diseases AMG].
AB  - Opportunistic infections are one of the major problem among HIV infected patients
      still connected with high mortality. The aim of the investigation is to evaluate
      the incidence and mortality from opportunistic infections in HIV infected
      population in Pomeranian region of Poland. The paper presents analysis of
      incidence of opportunistic infections among 141 AIDS patients hospitalised in
      Clinic for Infectious Diseases in Gdansk from 1988 to 2001/June/. In examined
      group 179 opportunistic infections were diagnosed. Most frequent was oesophageal
      candidiasis 58%, tuberculosis 29%, pneumocystis carinii pneumonia 21% and central
      nervous system toxoplasmosis 13%. The occurrence of opportunistic infections
      depends on CD4 count and rises with CD4 decline. Opportunistic infections were
      the reason of death in 33 from 74 cases/45%/. CONCLUSIONS: In examined group 28%
      of patients did not know about HIV infection when first opportunistic infection
      was diagnosed. Most frequent opportunistic infections in AIDS patients were
      oesophageal candidiasis, tuberculosis, pneumocystis carinii pneumonia and
      toxoplasmosis. In 98% of cases opportunistic infection developed when no HAART
      nor infection prophylaxis was administered. Opportunistic infection was the
      reason of death in 45% of cases, the most frequent were PCP and CNS
      toxoplasmosis.

PMID- 11984939
TI  - [Etiology, pathogenesis and treatment options in Kaposi's sarcoma of HIV
      infection].

PMID- 11984940
TI  - [Drug combination therapy for children infected with HIV/AIDS--own experience].
AB  - Background antiretroviral therapy (HAART) for primary perinatal infection with
      three drugs is recommended because it provides the best opportunity to preserve
      immune function and delay disease progression. The aim of HAART is to maximally
      suppress viral replication, preferably to undetectable levels. We evaluated the
      safety and efficacy of a three drug regimen in a small group 7 of maternally
      infected and 1 probably nosocomial infected children from 1998. METHODS: Triple
      drug combination regimen the most often was composed of: either AZT + 3TC + NFV,
      ddi + d4T + NFV, or ddI + d4T + NVP. This therapy was monitored by serial
      measurements of peripheral-blood CD4, viral load (VL), biochemical parameters and
      clinical observation. Lately also genotyping resistance and phenotyping drug
      susceptibility were investigated in the patients with high > 5000 kopii/ml VI.
      RESULTS: The three-drug regiment was well tolerated in 6/8 patients.
      Hematological abnormalities (severe anaemia after AZT) was noticed in 1 patient
      and hyperlipidemia in the second one (after Nelfinavir). 3TC resistance or
      genotyping mutations were observed in 4/8. These patients had low or undetectable
      VL during a long time, but lately after > 1 year therapy VL has risen. In all 8
      patients clinical and immunological parameters are good, stabile. The
      opportunistic infections weren't observed. CONCLUSIONS: Although further
      observations are needed., it appears that in HIV infected children combined
      treatment is well tolerated and has sustained efficacy against HIV.

PMID- 11984941
TI  - [Infective endocarditis in adults].
AB  - OBJECTIVE: The aim of the research was to demonstrate that the early diagnosis of
      infective endocarditis influences significantly the results of treatment.
      METHODS: The following clinical analysis covered 56 patients, aged 18 to 81 (the
      average age--50 years) with infective endocarditis treated in the years 1998
      2000. Data from patient history, physical examination, laboratory investigations
      and treatment were analysed. Apart from clinical symptoms for infective
      endocarditis diagnosis, also blood cultures and echocardiography were important.
      MAIN OBSERVATIONS: Infective endocarditis was present in 24 patients (42.8%) with
      heart defects, 7 (12.5%) with prosthetic heart valves, and 4 (7.1%) treated with
      haemodialysis. RESULTS: In 38 (67.8%) individuals, the echocardiography showed
      vegetations, and in 14 (25.0%) other abnormalities. Blood cultures were positive
      in 33 (58.9%) patients. Fever was present in 47 (83.9%) patients. The progression
      of heart failure appeared in 26 (46.4%) individuals. The average time of
      antibiotic therapy was 34 days. 11 (19.6%) patients died. 9 (16.1%) individuals
      had cardiosurgery operations. CONCLUSIONS: Early diagnosis of infective
      endocarditis is substantial as it improves patients' prognosis as to health and
      life.

PMID- 11984942
TI  - [The analysis of hepatitis B and hepatitis C in Swietokrzyski Voivodeship during
      years 1997-2000].
AB  - For many years sick rates of hepatitis B and hepatitis C are higher in
      Swietokrzyskie Voivodeship than in Poland. The morbidity of hepatitis B decreases
      from the level of 13.8 (12.49) in 1997 to 10.04 (6.97) in 2000. The lowest
      morbidity is in the group of children 0-6 years old, the highest in age group
      over 65. Differences of morbidity in towns and rural areas are not significant.
      The morbidity of hepatitis C is still growing from the level of 5.9 (2.58) in
      1997 to 14.96 (5.09) in 2000. The morbidity is higher in towns--8.43 in 1997 and
      23.22 in 2000, than in rural areas--3.58 in 1997 and 7.96 in 2000. As protracted
      cases were registered 45% cases of hepatitis B and 95% cases of hepatitis C.
      Acute cases of hepatitis B have documentary evidence of contact with health
      service in last 6 months. As a result of widespread vaccination against hepatitis
      B the number of cases decreases. The high sick rate of hepatitis B and nearly 3
      times higher than in Poland sick rate of hepatitis C manifests negligence of
      sanitary conditions, non observance proper medical practices and procedures, lack
      of hygienic habits in health service institutions and paradoxically, good
      diagnostics and registration of infectious diseases. *Morbidity in Poland.

PMID- 11984943
TI  - [Cellular expression of human cytomegalovirus (HCMV) in children with chronic
      hepatitis B].
AB  - OBJECTIVE: The study aimed at detection tissue expression of human
      cytomegalovirus (HCMV) in children with chronic type B hepatitis. MATERIAL AND
      METHODS: The studies were performed on liver biopsies obtained from 26 children
      with active HBV replication after excluding infection with other hepatotropic
      viruses. Control group consisted of liver biopsies obtained from 5 children with
      chronic hepatitis of other aetiology (HCV, HCMV, autoimmune hepatitis). The
      studies were performed employing immunocytochemical techniques of detecting the
      early viral antigen (HCMV-EA) and the in situ hybridisation to detect HCMV-mRNA
      and HCMV-DNA. MAIN OBSERVATIONS: Among 26 children with chronic type B hepatitis,
      presence of HCMV-DNA and HCMV-EA was demonstrated in one child. In the case, no
      HCMV-mRNA was detected in the tissue. In the control group, immunoreactivity for
      EA was noted in one child with HCMV-induced chronic hepatitis. Neither DNA nor
      mRNA of--HCMV could be noted in the tissue. In another child of the control group
      pronounced (in over 60% cells) expression of HCMV-DNA was demonstrated, in the
      absence of HCMV-mRNA and EA-HCMV. CONCLUSIONS: As shown by our studies, active
      HCMV infection in the liver in children with chronic HBV infection is a rare
      event and it does not deteriorate further histological pattern of the liver.
      However, effects of incomplete HCMV replication of extrahepatic localisation of
      viral particles on subsequent course of chronic hepatitis cannot be excluded.
      High effectiveness of the ImmunoMax technique should be stressed: the technique
      permitted to demonstrate even scanty amounts of the virus in the organ and in
      conditions of its incomplete replication.

PMID- 11984944
TI  - [Selected immunologic markers of HCV in children with chronic hepatitis B].

PMID- 11984945
TI  - [Dynamics of serum copper level in patients in the acute phase of hepatitis B and
      in early convalescence].
AB  - OBJECTIVE: Analysis of serum copper (Cu) level dynamics during the acute phase of
      hepatitis acute B and the early convalescence in compliance with gravity of the
      acute disease course. METHODS: The study included 39 patients (12 men and 27
      women), aged 18 to 76 years. They were hospitalised in the Department of
      Infectious Diseases of Medical Academy in Lublin because of the hepatitis acute
      B, without coexisting diseases. The diagnosis was based on the epidemiologic
      anamnesis, clinical symptoms, biochemical and serological examinations. The
      studied group was divided in respect to sex and the course of the disease as:
      light, medium-weighty and weighty. In all examined patients, the serum Cu level
      was determined according to the following scheme: at the first, tenth, twentieth
      and the last day of the hospitalisation and additionally one time at four weeks
      after discharging from the clinic. The serum Cu level was made by atomic
      absorption spectrometry (AAS) at the wave length of 324.8 nm. The received data
      were subjected to statistical analysis according to t-Student's test and in cases
      of significant differences according to the variants of c-Cochran and Cox's
      tests. According to the SI Unit Conversion Guide, the values 11.22 to 23.58
      mumol/l were taken as the normal range. The values derived from the control group
      of 24 healthy persons (13 men and 11 women) aged 22 to 69 years. RESULTS: The
      significant increase of serum Cu level in comparison with the control values was
      found both in the acute phase of hepatitis B and the early convalescence. It
      could be observed a correlation between serum Cu level and the course of
      hepatitis viralis acuta B.

PMID- 11984946
TI  - [Hepatocytes growth factor (HGF), leptin, neopterin serum concentrations in
      patients with chronic hepatitis C].
AB  - In 18 patients with chronic hepatitis C we evaluated leptin (with IRMA method)
      and HGF and neopterin (with ELISA method) serum concentrations. Concentrations of
      leptin, HGF and neopterin were higher than in the control group. Leptin serum
      concentrations correlated with liver biopsy inflammatory grading, but higher HGF
      concentrations were connected with fibrosis staging. Neopterin correlated with
      both parameters and GGTP activity. IN CONCLUSION: increased neopterin
      concentrations could inform about liver inflammation activity; leptin and HGF
      serum concentrations could reflect the liver damage intensity.

PMID- 11984947
TI  - [Progression of treatment of hepatitis C--peginterferon].

PMID- 11984948
TI  - [Hepatitis B virus vaccination among Polish surgeons from the county of Western
      Pomerania].
AB  - Orthopaedic surgeons are at risk of acquiring hepatitis B virus, so preventive
      measures, including the vaccination, are important. OBJECTIVE: To determine
      surgeons" prevention through vaccination against hepatitis B and to access the
      frequency of "sharps" injuries during surgery. METHODS: An anonymous
      questionnaire prepared by A. Lowenfels from New York Medical College, USA was
      distributed between May and July 2001 to 182 members of surgical staff. Twelve
      hospitals located in the city of Szczecin (4 academic, 4 municipal) as well as
      located within a 45-mile radius in the county of Western Pomerania, Poland took
      part. RESULTS: 9.3% of the surgeons who responded had been infected with
      hepatitis B virus (group I), 79.7% had been immunised against hepatitis B (group
      II). The rest 11%, mainly of the age > 47 years, had never been vaccinated nor
      infected (group III). The median number of puncture injuries was 10 per year and
      the number of hours spent in the operating room--59 per month. There was no
      statistically significant difference in the variables such as: sex, surgical
      status, sub-specialty or type of hospital between the groups. CONCLUSIONS: The
      coverage with the vaccine should be improved. A lot of surgeons who replied take
      high risk of percutaneous blood exposure and thus possibility of infection with
      HBV, but every tenth has never been vaccinated nor infected. The complete
      information on the risk of hepatitis B and on the safety and efficiency of active
      immunisation should be supplied not only among medical students, but surgical
      experienced staff as well.

PMID- 11984949
TI  - [Bacterial meningitis in children in Poland--multicenter study ].

PMID- 11984950
TI  - [Epidemiologic aspect of lyme borreliosis among the inhabitants of Podlasie
      Province].
AB  - The aim of this study was to evaluate Lyme borreliosis morbidity among the
      inhabitants of Podlasie Province in the years of 1996-2000. MATERIAL AND METHODS:
      The new cases of Lyme borreliosis reported in the years of 1996-2000 in Podlasie
      Province were analyzed. The analysis included the data from Mz-56 and Mz-57 forms
      and the information from epidemiologic investigations sent to Regional Sanitary
      and Epidemiologic Station in Bialystok. In 1996-2000, screening examinations were
      carried out in the same group of 358 forestry workers including 44 (12.29%)
      females and 314 (87.71%) males aged from 21 to 64 (x = 41.2) years.
      Immunoenzymatic test of ELISA Borrelia recombinant IgM and IgG by Biomedica firm
      (Austria) were used to detect B. burgdorferi antibodies. RESULTS: In 1996-2000,
      4933 of borreliosis cases were registered in Poland including 1377 (27.91%) in
      Podlasie Province. The morbidity rate in Podlasie province ranged from 15.05% in
      1996 year to 21.29% in 2000 year of the whole country morbidity. At the same
      time, the incidence rate in Podlasie Province ranged from 9.09 in 1996 to 32.2 in
      2000 year and was 6.72-fold higher than the incidence rate in the whole country.
      In Eastern and Central region of the province, 80.54% of cases were registered
      whereas, 14.09% by the Lakeside of Augustow and Suwalki only 5.37% in the western
      region of the province. It was proved that the morbidity increased in proportion
      to the age of patients (41.39% of patients were at the age of 30-49) and it
      decreased only above the age of 60. Thus, Lyme borreliosis affects mainly people
      at working age. The increase in B. burgdorferi antibody detectability was noticed
      in the population of forestry workers; it was detected in 38.55% in 1995 and in
      2000 in 43.56% of the examined. Interestingly, 81 people infected with B.b in
      1995-2000 included 74 men and only 7 women, supporting the statement that B.b
      infection affects mainly working professionals and the risk increases with the
      practice. CONCLUSIONS: Our studies indicate that Lyme borreliosis is a serious
      health problem among the inhabitants of Podlasie Province which is an endemic
      area for Ixodes ricinus ticks infected with B. burgdorferi spirochete.

PMID- 11984951
TI  - [Are all diseases caused by infections?].

PMID- 11984952
TI  - [New public health approach to STIs prevention].
AB  - International Conference on Population and Development (1994) recommended that
      the scope of reproductive health should be broadened beyond family planning and
      maternal care. It should include prevention and management of HIV/AIDS/STIs and
      many others issues. The arguments for this shift and some organizational rules
      for health reproductive system performance are presented.

PMID- 11984953
TI  - [Vegetations associated with infective endocarditis in children].
AB  - OBJECTIVE: The purpose of this study were clinical analysis of vegetations
      associated with infective endocarditis. MATERIAL AND METHODS: Between 1990-1999
      years 7 children (aged 2-17 years) with infective endocarditis were study in the
      Cardiology Department Children's Memorial Health Institute. Analysed clinical
      features of vegetations associated with endocarditis. MAIN OBSERVATIONS AND
      RESULTS: The most of them vegetations were localized on the mitral valve and in
      children without congenital heart disease (CHD). Remaining patients were: girl
      with bicuspidal aortic valve-vegetation on the aortic valve, boy with simple
      ventricle, pulmonary stenosis and atrial septal defect-vegetation on the
      pulmonary valve, boy with double outlet right ventricle, pulmonary stenosis and
      atrial septal defect-vegetation on the tricuspid valve, boy with patent ductus
      arteriosus-vegetation on the pulmonary valve. In all patients were regurgitations
      of this valves (> II degree). 71% patients had fever, 57% another murmur in the
      heart, 43% hepatosplenomegalia. Positive result of the blood sowing was in 72%
      patients. After medical treatment of vegetations good result was in 4 children.
      Chirurgical treatment were performance in 3 children. CONCLUSIONS: 1. Vegetations
      in the echocardiographic examination were in 21.8% children associated with
      infective endocarditis. 2. The most of them vegetations were localized on the
      mitral valve and in children without CHD. 3. Good result after medical treatment
      of vegetations was in 57% patients.

PMID- 11984954
TI  - [Etiology and course of sepsis in adult patients treated in the Department of
      Infectious Diseases, Medical University of Lodz--two-year observation].
AB  - Results of treatment of 22 adults hospitalized for sepsis in Intensive Care Unit
      of Department of Infectious Diseases, Medical University of Lodz, are presented.
      Etiology, confirmation of diagnosis according to common microbiological criteria,
      source of sepsis and final results of treatment were analysed. There were 14
      death among these patients (63.6%). In 50% of cases methycillin-resistant
      Staphylococcus aureus (MRSA) was the infectious agent.

PMID- 11984955
TI  - [Sepsis in HIV-positive patients--own observation].
AB  - In the period of 1988-2001 (June) 24 HIV-positive patients with symptoms of
      sepsis were observed. Most of them (17 persons) were intravenous drug addicts,
      six patients were infected HIV trough sexual contact and one person-via blood
      transfusion. There were 26 cases analyzed (one of the patients went trough three
      episodes of sepsis). Bacterial sepsis dominated (22 cases). In three patients
      fungoid etiology was diagnosed, and one case was of mixed character. The highest
      risk factors of sepsis were: intravenous drug addiction and advanced stage of HIV
      infection.

PMID- 11984956
TI  - [Infections as complications of blood transfusion]].

PMID- 11984957
TI  - [Monitoring of bacteremia in oncological patients].
AB  - The aim of the present study was analysis of bacteremia occurring among
      oncological patients treated in 3 departments of Regional Center of Oncology, in
      period 1997-2000. A total number of 255 blood cultures from 89 patients were
      tested using the automatic system to early detection of positive blood-cultures
      Bactec 9050 (Becton Dickinson). The strains were identified in the automatic
      VITEK system using commercial strips with biochemical tests and in manual system
      API (bioMerieux). The total number of positive blood cultures was 70 (27.45%).
      The most frequently isolated causal agents were the Gram-positive microorganisms
      (65.79%). Among 28 examined patients with positive blood cultures 10 were with
      lymphoma and 9 with cancer of the gastrointestinal tract. 9 patients (32.14%) had
      sepsis, 4 patients with sepsis died. Constant monitoring of bacteremia in
      oncological patients should be fundamental element in control of hospital
      infection program.

PMID- 11984958
TI  - [Epidemiology of infections after liver transplantation in children].
AB  - One of the most important problems after solid organ transplantation including
      liver, remains infections. Multiple risk factors play a role among which the most
      important are: general patients health before transplantation, prolong operative
      time, graft function and type of immunosuppression. The most important problems
      with bacterial, fungal and viral infections was described as well as treatment
      and profilaxis.

PMID- 11984959
TI  - [Epstein-Barr virus infection in patients after bone marrow and heart
      transplantation].
AB  - Epstein-Barr virus (EBV) infections in immunosuppressed patients cause the severe
      clinical problems. Posttransplant lymphoproliferative disease (PTLD) might occur
      as a result of the latent EBV activation. OBJECTIVE: Occurrence of active EBV
      infection in heart and bone marrow transplant patients. METHODS: 68 serum samples
      obtained from 13 allogenic bone marrow and 20 heart transplant patients were
      tested by IF and ELISA methods. Antibodies against VCA, EA and EBNA antigens were
      measured. RESULTS: All patients showed the presence of anti-VCA IgG antibodies,
      thus all were seropositive. Three patients (9%) showed primary EBV infection
      while in 12 (36%) patients virus reactivation or reinfection was confirmed.
      CONCLUSIONS: 1. EBV infection in immunosuppressed patients is mainly caused by
      latent virus reactivation. 2. Type of EBV infection can be confirmed
      serologically only by the detection of specific anti-VCA, EA and EBNA antibodies.
      3. The risk of PTLD in transplant patients creates the need for frequent
      monitoring.

PMID- 11984960
TI  - [B Streptococcus and other pathogenic bacteria colonization in hospitals in the
      Gdansk Metro Area].
AB  - A survey of group B Streptococcus and other pathogenic bacteria colonization was
      carried out on 658 neonates in 8 neonatal wards of hospitals in the Gdansk Metro
      Area and the district of Gdansk. Out of pathogenic bacteria Haemophilus and
      enteric bacteria the most frequently were isolated. The percentage of
      Staphylococcus aureus was relatively low (19.4). The group B Streptococcus
      frequency in throat was established as 3.8% and ranging from 1.7 to 8.8% in
      particular wards. In two cases group B streptococcus were not isolated. In probes
      taken from anus of newborn tested typical enteric flora dominated and E coli and
      Klebsiella sp were the most frequently encountered. Profile and frequency of
      bacterial colonization indicated that epidemiological situation in majority of
      particular wards in similar.

PMID- 11984961
TI  - [Iatrogenic streptococcal sepsis-- a case report].
AB  - A case study of iatrogenic streptococcal sepsis is presented. That was caused by
      the stomatological device left in a dental alveolus at time of dental treatment
      and prosthetic restoration. Systemic inflammatory response because of dentigenous
      spread endangered the patients life.

PMID- 11984962
TI  - [Usefulness of plasma C-reactive protein (CRP) estimation in patients with
      bacterial sepsis].
AB  - Between 1997-2000 there were 30 patients with bacterial sepsis treated at
      Department of Infectious Diseases of Silesian Medical University School in Bytom.
      Neisseria meningitidis (23.33%), Streptococcus pneumoniae (20%) and
      Staphylococcus aureus (3.33%) were most frequent etiological factors of the
      disease. The etiology of sepsis was not revealed in 53.34% of cases. Clinical
      state of patients was assessed using SSS and SAPS II score. All subjects were
      divided into two groups: group I--patients with septic syndrome symptoms (11
      cases), group II--patients without septic syndrome symptoms (19 cases). The aim
      of the study was usefulness of plasma C-reactive protein estimation in the course
      of bacterial sepsis monitoring. Plasma CRP concentration was assessed by
      immunoturbidometric method (using RANDOX, UK kits). Blood samples were taken on
      th 1., 4. and 10. day of therapy. Plasma CRP levels were statistically
      significantly higher in patients of the group I in samples of the first and the
      second assay. CRP serum concentration correlated with severity of a patient's
      clinical state. Type of sepsis's etiological factor did not exert influence on
      plasma CRP level. In fatal cases high plasma CRP concentration was recorded
      during the whole time of hospitalization, whereas in cases of recovery fast
      decrease of this protein level was noted. The obtained result indicate, that
      estimation of plasma CRP concentration in patients with bacterial sepsis may be
      helpful in evaluation of clinical state severity, monitoring of the disease
      course as well as therapy efficacy.

PMID- 11984963
TI  - [Immunity to infection. Infection in primary immunodeficiency].
AB  - The human body has an elaborate system of local and systemic, immune (cellular,
      humoral) and nonimmune (skin, mucous membranes) defense mechanisms to protect
      itself against microbal invaders. Disorders of this intricate system of host
      defense may generally be classified as primary or secondary. Unusual pathogens
      infect immunocompromised hosts. Ubiquitous organisms can become opportunistic
      pathogens. Reactivation of latent organisms is common in this group of patients.
      Despite their unusual features, infections in the primary immunodeficiency do not
      occur in a haphazard fashion but rather are predictable depending on the type of
      immune defects.

PMID- 11984964
TI  - [The role of pathomorphology in treatment of infections].

PMID- 11984965
TI  - [Clinical and bacteriological aspects of treatment of infection].

PMID- 11984966
TI  - [Treatment of severe sepsis and septic shock--are antibiotics the only remedy to
      treat infections?].

PMID- 11984967
TI  - [Severe infections and sepsis--the rules of empirical chemotherapy].

PMID- 11984968
TI  - [The essence of infection by opportunistic microorganisms].
AB  - Infection is regarded as an imbalance between microbial pathogenicity factors and
      the host defense systems. Opportunistic infections are defined as infections
      rarely observed in humans with normal immune responses. The term
      immunocompromised (compromised) host refers to host in which one or more defence
      mechanisms are inactive and in which the probability of infection is therefore
      increased. Hospital patients are often compromised host. Compromised hosts exist
      even outside the hospital (smoking, intravenous drug use, poor nutrition and
      other). A good example is HIV (human immunodeficiency virus). HIV causes acquired
      immunodeficiency syndrome (AIDS) by destroying the CD4 T lymphocytes, involved in
      the immune response. The most common AIDS-associated opportunistic infections
      include pneumonia caused by the fungus Pneumocystis carinii, systemic candidiasis
      (Candida albicans) and cryptococcosis (Cryptococcus neoformans), protozoal
      infections such as cryptosporidiosis (Cryptosporidium spp.) and toxoplasmosis
      (Toxoplasma gondii), viral infections due to HSV, CMV, EBV, HPV or HHV8,
      tuberculosis and other bacterial infections. Pneumocystis carinii pneumonia (PCP)
      is the most common opportunistic disease observed in AIDS patients. Disease does
      not necessarily follow exposure to a given causal agent (pathogen 01
      opportunistic pathogen). In fact, the occurrence (or otherwise) of disease
      typically depends on various factors--including the degree of sensitivity of the
      host (as above) and the virulence factors of the pathogens. Overtly aggressive
      products such as toxins and aggressins are clearly virulence factors. However, so
      too are those products and strategies which help a pathogen to become established
      in the host and to evade the host's defences. Certain virulence factors can be
      induced in the pathogen via signal transduction pathways from environment.

PMID- 11984969
TI  - [Chronic fatigue syndrome, an unappreciated syndrome].

PMID- 11984970
TI  - [Humanism and medicine].
AB  - WITH THE PROGRESS MADE IN KNOWLEDGE AND TECHNIQUES: Therapeutic efficacy has
      advanced. However, interrogations concerning the control of the power that is
      conferred and the new obligations towards patients that stem from this progress
      have emerged and, further to the sinister ethical deviations in medical research
      and testing, and the supreme temptation that is represented by the money
      involved, questioning has increased. THE NUREMBERG CODE: Promulgated in December
      1947, is the founder text of modern biomedical ethics. Subsequently completed by
      numerous other international conventions, it established the principle of
      voluntary, informed consent, therefore confirming the autonomy of the patient and
      the respect that is due from the physicians. However, questions arise not only
      regarding the foetus and embryo, but also regarding those reaching the end of
      their lives. CONCERNING EMBRYOS: No contradiction is apparent between the
      singularity of the human embryo and the use of embryos destined to be destroyed
      in highly scientific and moral quality research projects. With regard to the
      development of methods for producing cloned human embryos, it appears to be
      associated with greater risks than establishing urgent and necessary steps
      towards fulfilling the promises of regenerating medicine. Last but not least,
      deviations in reproductive biology and clinical trials conducted in this field,
      with relentless procreation and "human studies", must be denounced. AT THE OTHER
      END OF LIFE: It is worrying to note the apparent facility with which our
      societies consider that old age is an indignity. To call knowledge a 'power' is
      to consider that such power can be used not only to relieve suffering but also to
      manipulate others. The humanistic finality of an intention is not sufficient to
      guarantee neither its benignity nor its morality.

PMID- 11984971
TI  - [Incidence of acute cor pulmonale and deep venous thrombosis in acute pulmonary
      embolism].
AB  - OBJECTIVE: Ultrasounds are a useful tool when looking for indirect evidence in
      favor of pulmonary embolism. The aim of this study was to determine the incidence
      of acute cor pulmonale and deep venous thrombosis revealed by ultrasonographic
      techniques in a population of patients presenting with pulmonary embolism.
      METHODS: 96 consecutive patients with a mean (+/- SD) age of 65 +/- 15 years,
      admitted to our hospital for pulmonary embolism were included in this study. The
      diagnosis of pulmonary embolism was made either by spiral computed tomography or
      selective pulmonary angiography. Each patient subsequently underwent both trans
      thoracic echocardiography and venous ultrasonography. The diagnostic criterion
      used for defining acute cor pulmonale by echocardiography was the right to left
      ventricular end-diastolic area ratio over (or equal to) 0.6. Diagnosis of deep
      venous thrombosis was supported by the visualization of thrombi or vein
      incompressibility and/or the absence of venous flow or loss of flow variability
      by venous ultrasonography. RESULTS: Using ultrasounds, an acute cor pulmonale was
      found in 63% of our patients while 79% were found to have deep venous thrombosis
      and 92% of the patients had either acute cor pulmonale or deep venous thrombosis
      or both. All of the patients with proximal pulmonary embolism had acute cor
      pulmonale and/or deep venous thrombosis. The presence of acute cor pulmonale on
      echocardiography was significantly higher in patients with proximal pulmonary
      embolism (p < 0.0001). CONCLUSION: This study emphasizes the potential value of
      ultrasonographic techniques in the diagnosis of acute pulmonary embolism.

PMID- 11984972
TI  - [Chylothorax and malignant pleurisy, little known effusions].

PMID- 11984973
TI  - [Chylothorax].
AB  - PHYSIOLOGY: Chylothorax corresponds to the intrathoracic presence of chyle. Chyle
      is a lymph of intestinal origin containing the product of digested fat. This
      lymph joins the blood circulation through the thoracic duct. The thoracic duct
      receives a part of the lymphatic drainage from the viscera below the diaphragm,
      from the diaphragm and from the sterno-costal wall. PHYSIOPATHOLOGY: Intrapleural
      chyle issue is explained by an acquired or spontaneous lesion of the thoracic
      duct or of one of its collaterals in the thorax. The iatrogenic or spontaneous
      lesions of the collaterals suggest that the latter are incontinent and have lost
      their valve capacity, and hence provoke a reflux of chyle from the thoracic duct.
      The anatomy of the chylothorax (occasionally pathological) can be specified by a
      pedal lymphography. FROM A THERAPEUTIC POINT OF VIEW: Treatment, essentially
      medical, can be completed by surgery. The medical treatment is based on re
      nutrition and a diet excluding fat, supplemented by medium chain triglycerides.
      Surgery consists in pleural symphysis and/or suture of the damaged collaterals,
      or ligature of the thoracic duct. The indications depend on the severity of the
      chyle leakage and the type of original lesion. The indications therefore depend
      on the etiology and clinical evolution of each case. These different treatments,
      isolated or combined, lead to the regression of the effusion in nearly all cases.

PMID- 11984974
TI  - [Secondary tumoral pleurisy].
AB  - WHEN THE PRIMARY CANCER IS KNOWN: Secondary tumoral pleurisy can develop at any
      stage in the evolution of a neoplastic disease and its diagnosis is easy when the
      primitive cancer is known. Cytological analysis of the pleural liquid and/or
      biopsy often provides material and the slides can then be compared with those of
      the primitive cancer and a relationship established. However, a probabilistic
      diagnosis should not be in haste, without anatomopathological confirmation, since
      the causes of pleurisy in a cancer patient are varied. WHEN THE PRIMARY CANCER IS
      NOT KNOWN: The most difficult situation is that when the pleurisy is revelatory
      of a neoplastic disease. In this case, explorations should be limited to a few
      essential examinations guided by the clinical profile, without being tempted to
      carrying out exhaustive explorations of the primitive cancer, which would not
      change the prognosis. Before such explorations, it is essential to obtain a
      precise pleural diagnosis, and for this, the indication for a pleuroscopy must be
      easily and rapidly accessible. FROM A THERAPEUTIC POINT OF VIEW: Once the
      diagnosis of pleurisy has be established, treatment is in two parts, associated
      or not: local treatment consisting in pleural sympysis and general treatment
      (chemotherapy or even hormone therapy, adapted to the primitive neoplasia).
      Pleural sympysis is often performed using talc, either during the pleuroscopy
      (talc insufflated under visual control), or during thoracic draining (talc
      slurry).

PMID- 11984975
TI  - [Effect of almitrine/raubasine on cerebral metabolism in the elderly].
AB  - Recent neurobiological data has led to renewed interest in oxygen (O2). The
      discovery of neuroglobin, protein varyingly present in the brain, has been
      enhanced by the elucidation of the mechanisms through which oxygen intervenes in
      neuronal metabolism. Almitrine/raubasine activates the metabolism of
      hypoxic/ischemic neurones by increasing O2 bioavailability. This mechanism
      supports the effects on behaviour obtained in various animal models and the
      benefits observed during clinical trials in elderly patients presenting with
      cognitive defects.

PMID- 11984976
TI  - [Bioethics and the 21st century, viewpoint of the jurist].
AB  - It is essential to approach the question of protection of human life from a legal
      point of view, because the developments in reproductive biology and the new
      research fields on the embryo and the so called 'stem' cells, imply the
      establishment of new laws. This is a real challenge, since to infer rights to the
      onset of life means that the embryo or the foetus has to have a status. The
      European Ethics Group has to provide propositions concerning the ethical aspects
      of embryo research, related to research on the 'stem' cells. In fact, Europe is
      confronted with several problems related to the cultural, legal and religious
      pluralism and the market regulations. Reflections on embryos must no longer be
      based on the search of means to improve reproduction techniques, but on their use
      as simple cell producers. Some suggestions can be made in favour of a mutual
      European approach to bioethics: research and medicine devoted to the onset of
      life must be submitted to strict public control; the status of the embryo must be
      clarified; recommendations have to be drawn-up regarding so-called 'therapeutic'
      cloning; and International laws concerning bioethics must be established.

PMID- 11984977
TI  - [Hospital intern, what title for which training?].

PMID- 11984978
TI  - [Internship, an essential learning period (interview by Veronique Girault)].

PMID- 11984979
TI  - [Chronology of 2 centuries of internship].

PMID- 11984980
TI  - [Screening and follow-up of nosocomial infections by multiresistant bacteria
      using the Bacterio software. Microbiology laboratory data].
AB  - OBJECTIVE: To study the relationship between the prevalence of multi-resistant
      bacteria (MRB) and nosocomial MRB infections. METHOD: This work presents the
      results of a follow up of hospital-acquired infections due to multidrug-resistant
      bacteria (MRB), based on microbiology detection with the Bacterio software and
      clinical confirmation. RESULTS: Clinical responses reached 93%. During the year
      2000, the incidence of hospital-acquired MRB infections was 1.23 for 1000
      hospitalization days and 1.00 for 100 admissions. Ticarcilline-resistant P.
      aeruginosa were responsible for 32% of hospital-acquired MRB infections. The
      incidence curve of MRB colonization was parallel with that of hospital-acquired
      infections. Hence, the incidence of MRB colonization is a rapid and good means of
      assessing the best probabilistic antibiotherapy especially in intensive care
      units. COMMENTS: Examination of medical records is however necessary to obtain
      complementary clinical information on: risk factors, use of medical devices,
      medical or chirurgical antecedents and prior antibiotherapy. The easiness of
      detection and management of hospital-acquired infections allowed us to extend its
      use in 2001 to the follow-up of all hospital-acquired infections, with or without
      MRB. Bacterio is also able to detect the hospital-acquired infections that,
      according to the recent decree (No. 2001-671, july 30th, 2001), must be declared
      to the sanitary authorities. Such suspicions should then be validated by the
      clinicians and the practising hygienist.

PMID- 11984981
TI  - [Indication for labor induction by prostaglandin E2 vaginal gel. Retrospective
      study of a continuous series of 170 patients].
AB  - OBJECTIVE: To assess the factors of efficacy, side effects and complications
      following vaginal application of prostaglandin E2 (PGE2). METHODS: Retrospective
      study of 170 women in whom a PGE2 vaginal gel was administered between June 1,
      1999 and June 1, 2000. The efficacy (labor effectively induced), quality of
      myometrial response, side effects and complications were studied globally and in
      each clinical context: intra-uterine delayed growth (IUDG), pre-eclampsia without
      IUDG, diabetes, pregnancy prolonged without IUDG, anomaly in fetal heart rate
      (FHR) and/or in amniotic liquid without IUDG discovered during the systematic
      monitoring at the end of pregnancy, premature rupture of the membrane without
      IUDG. RESULTS: The overall success (defined as the onset of labor) was of 94.1%.
      This rate was of 90.7% in primiparous and of 100% in multiparous women. Twenty
      three patients (13.5%) experienced side effects (hyperkinesia or hyperthermia)
      and 35 patients (20.6%) complications (hyperkinesia or hypertonia with fetal
      repercussion). The maternal-response to infection was significantly improved (p <
      0.05) in cases of prolonged rupture of the membranes or anomaly discovered during
      monitoring, but only in patients with diabetes. In cases of IUDG of vascular
      etiology with multiparity, the total quantity of PGE2 necessary was only of 1.14
      mg and 85% of patients subsequently delivered without ocytocine. CONCLUSION: IUDG
      and prolonged pregnancy are the principle indications for PGE2 vaginal gels. The
      quality of response depends on the clinical context. In cases of premature
      rupture of the membranes or of anomaly discovered during monitoring (FHR and
      amniotic liquid), response was only improved in diabetic patients. In cases of
      vascular IUDG and multiparity, the response was excellent and the majority of
      women subsequently delivered without ocytocine, thus confirming the quality of
      myometrial response. Hence, the quantity of PGE2 required varied, depending on
      the subjecent pathology. This strategy could limit the risk of excessive
      myometrial response (hyperkinesia or hypertonia) and thus improve fetal
      tolerance.

PMID- 11984982
TI  - [Treatment of severe botulism with 3,4-diaminopyridine]].
AB  - INTRODUCTION: The specific treatments of botulism with serotherapy and with
      guanidine are of debatable efficacy. We report a case of nutritional toxin B
      botulism successfully treated with 3,4-diaminopyridine. OBSERVATION: Following a
      meal, a 69 year-old woman consulted for digestive disorders followed by damage to
      several cranial pairs, autonomous nervous system and ventilation command,
      motivating mechanical ventilation on tracheal intubation. Administration of
      symptomatic treatment with 3,4-diaminopyridine led to progressive improvement,
      although the diagnosis of toxin B botulism was confirmed. COMMENTS:
      Administration of 3,4-diaminopyridine, the efficacy of which had been suggested
      by the review of experimental literature, led to rapid and clear improvement,
      probably due to its potentiating effect on acetylcholine release in the
      neuromuscular junction.

PMID- 11984983
TI  - [Portal vein thrombosis and Prevotella melanigenica revealing an appendicular
      abscess].
AB  - INTRODUCTION: The misleading aspects of appendicitis are multiple. We report an
      observation, original not only from a clinical and bacteriological point of view
      but also because of the presence of a portal vein thrombosis. OBSERVATION: A 48
      year-old man was hospitalized for prolonged fever. Examination revealed a
      thrombosis of the portal vein. Several hemocultures were positive for Prevotella
      melaninogenica. There was no abnormality in blood crasis and/or thrombophilia.
      Since the digestive and endoscopic control was negative, as well as the
      scanographic and sonographic exploration of the appendix area, exploratory
      laparotomy was performed and revealed an abscess on the appendix, which was
      responsible for the clinical, biological and radiological images. Appendectomy
      led to complete, immediate and permanent regression of the fever. COMMENTS: The
      discovery of a Prevotella-type germ disputes the pathogenicity of such an
      anaerobic germ, at distance from a site where it is normally saprophyte.

PMID- 11984984
TI  - [Ivermectin, a broad spectrum antiparasitic drug].
AB  - ACTIVITY: Ivermectine, derived from beta avermectines, monocyclic lactones
      produced by Streptomyces avermitilis, is a potent oral microfilaricide used by
      veterinaries since 1981. The anti-filarial activity is two-fold: both
      microfilaricide and embryotoxic in female adults; it has no activity on the
      latter. INDICATIONS: Ivermectine is the treatment of choice in onchocercosis,
      induced by the nematode Onchocerca volvulus, and was included in the
      onchocercosis control program (programme de controle de l'onchocercose (OCP) in
      1987. Ivermectine has also demonstrated efficacy on other filaries (Wuchereria
      bancrofti, Loa loa), in intestinal nematodes (Ascaris lumbricoides, Strongyloides
      stercoralis) and in parasite nematodes in man (larva migrans ankylosis).
      ACCORDING TO THE RESULTS OF RECENT STUDIES: Its activity has been recently
      extended to ectoparasitosis: sarcoptes and pediculosis of the scalp.

PMID- 11984985
TI  - [Cytosteatonecrosis of the newborn infant].
AB  - CHARACTERISTICS: Cytosteatonecrosis of the newborn (CSNN) is an acute
      hypodermatitis that appears within the first four weeks of life. It essentially
      develops in infants born at term or postmature, and following a difficult
      delivery. THE LESIONS: The lesions are more or less extended sub-cutaneous
      nodules or inflammatory plaques on the body that regress spontaneously, without
      after effects, within one to four months. A cutaneous biopsy, rarely required for
      diagnosis, reveals a granulomatous reaction to a foreign body in a necrosed
      subcutaneous adipose tissue. EVOLUTION: Although the progression is generally
      benign, it may be complicated by the occurrence of hypercalcemia. The management
      of these infants justifies the regular monitoring of blood calcium levels and
      treatment of an eventual hypercalcemia.

PMID- 11984986
TI  - Advancements and opportunities in sterilisation.
AB  - Radiation sterilisation often significantly degrades polymers. This article
      reports on a study that compares materials degradation after sterilisation by
      gamma and electron beam (E-beam). Also, in a discussion of the mechanisms of
      thermal processing by steam autoclave, ways to enhance product quality are
      presented.

PMID- 11984987
TI  - Experiences with microbiological validation of radiation sterilisation.
AB  - Apart from process control, the two most critical activities associated with
      radiation sterilisation of medical devices are the dosimetric and microbiological
      analyses required to validate the process. This article discusses some of the
      problems experienced in the field of microbiological validation and highlights
      the coming changes to the standards.

PMID- 11984988
TI  - The technological edge.
AB  - A new 3D system that employs autostereoscopic display and an eye-tracking device
      will improve the safety of laparoscopic surgery.

PMID- 11984989
TI  - Update on ISO 13485.
AB  - A previous article discussed the impact that new quality management system
      standards are likely to have on the CE-marking process. The draft international
      standard for medical device quality systems has now been published. This article
      will discuss important issues related to the new standard.

PMID- 11984990
TI  - Regulatory barriers to tissue-engineered products.
AB  - Autologous tissue-engineering technology uses the body's own regenerative
      capacity to solve clinical problems. Human cellular- and tissue-based products
      include an array of medical products for repair, reproduction, replacement and
      other therapeutic purposes. However, the lack of European Union regulation for
      these products is putting the future of the technology at risk in Europe.

PMID- 11984991
TI  - Standards in the 21st century. Standards and new technologies.

PMID- 11984992
TI  - Micromachining.
AB  - Components and features can be made in a number of ways. This article describes
      the different micromachining processes and what they can achieve in terms of
      precision, repeatability and cost savings.

PMID- 11984993
TI  - In search of the ideal bone graft.
AB  - This summary of materials used to replace bone describes polymer developments and
      suggests the route to finding the ideal graft material. This includes a look at
      the potential of bone morphogenetic proteins.

PMID- 11984994
TI  - Switzerland: research themes in orthopaedics.

PMID- 11984995
TI  - Catheters, materials and infection.
AB  - The possible influence of catheter material on infection rates, particularly in
      relation to the use of central venous catheters, has been a controversial matter
      for many years. Some of the factors that control the occurrence of infection are
      considered in this article.

PMID- 11984996
TI  - [Atrial fibrillation: conversion to sinus rhythm?].

PMID- 11984997
TI  - [Bone marrow examination].

PMID- 11984998
TI  - [Maturity-onset diabetes of the young--MODY. Molecular-genetic,
      pathophysiological and clinical characteristics].
AB  - Maturity-onset diabetes of the young (MODY) is a genetically and clinically
      heterogeneous subtype of type 2 diabetes characterised by an early onset, an
      autosomal dominant inheritance, and a primary defect in insulin secretion. MODY
      comprises 2-5% of cases of type 2 diabetes. So far, six MODY genes have been
      identified (MODY1-6): hepatocyte nuclear factor (HNF-4 alpha), glucokinase, HNF-1
      alpha, HNF-1 beta, insulin promoter factor 1(IPF-1), and neurogenic
      differentiation factor 1 (NEUROD1). MODY2 and MODY3 are the most common forms of
      MODY. Mutations in glucokinase/MODY2 result in a mild form of diabetes. In
      contrast, MODY3 and some of the other MODY forms are characterised by major
      insulin secretory defects and severe hyperglycaemia associated with microvascular
      complications. About 25% of known MODY is caused by mutations in yet unknown
      genes and present results suggest that other monogenic forms of type 2 diabetes
      might exist. The diagnosis of MODY has implications for the clinical management
      of the patient's diabetes. The identification of MODY genes also opens new
      perspectives in the understanding of the molecular basis of diabetes and may
      probably contribute to the definition of novel targets for drug development and
      gene therapy.

PMID- 11984999
TI  - [The effect of metformin on late diabetic complications and cardiovascular events
      in obese patients with type 2 diabetes].
AB  - The aim of this review, after a short presentation of the United Kingdom
      Prospective Diabetes Study (UKPDS), is to stress that metformin is the drug of
      choice for overweight type 2 diabetic patients. The effect of metformin on
      various cardiovascular risk factors is briefly discussed.

PMID- 11985000
TI  - [Metformin. Mode of action and effect of monotherapy and combination therapy on
      glucose metabolism in type 2 diabetes].
AB  - The aim of the review is to give a short presentation of the pharmacological
      properties and effectiveness of metformin. Existing evidence for the clinical use
      of metformin, both in monotherapy and in combination with other classes of anti
      diabetics, is discussed. Overall, metformin presents a very favourable profile in
      the treatment of type 2 diabetes.

PMID- 11985001
TI  - [Steadily changing food consumption of Danes. Clear trends during the period 1995
      2001].
AB  - INTRODUCTION: The aim of the study was to describe trends in food habits in
      Denmark derived from a food frequency survey conducted by the Danish Nutrition
      Council in 2001 and compare it to similar surveys from 1995 and 1998. MATERIAL
      AND METHODS: A random population sample of 1000 men and women (aged 15-91 years)
      were interviewed by telephone. They were asked 13 food frequency questions about
      nutritionally important foods (yoghurt, milk, cheese, rye bread, wheat bread,
      sandwiches with fish, fish as the main meal, meat as the main meal, potatoes,
      rice/pasta, vegetables (two questions) fruit) and about the type of milk and fat
      spreads most often used. RESULTS: Several of the changes seen from 1995 to 1998
      had continued into the 1998-2001 period. The results showed increased frequencies
      for shredded salad/raw vegetables and rice/pasta, but reduced frequencies for
      meat as the main meal and potatoes. Fruit consumption had also increased between
      1998 and 2001. Average frequencies differed by 13-28%. Another pronounced trend
      was the increased use of low-fat milk (< or = 0.5% fat) instead of whole milk
      (42% drinking low-fat milk in 2001 versus 28% in 1998) and the greater numbers
      who did not spread any kind of fat on their bread (40% versus 22% in 1995, for
      rye bread). DISCUSSION: In general the observed trends point in the right
      direction in respect of food-based dietary guidelines and other recommendations.
      This indicates that the Danish population has been influenced by the nutritional
      messages and campaigns stressing fat reduction and increased intake of fruit and
      vegetables. An important factor in this context is the increasing availability of
      low-fat milk products on the Danish market. Whether or not the positive trends
      for foods included are supported by the rest of the diet remains to be answered.

PMID- 11985002
TI  - [Upper airway obstruction in thyroid diseases].
AB  - INTRODUCTION: Respiratory symptoms (stridor) in thyroid diseases are rather
      common, but often overlooked, especially in older people in whom they may be
      misinterpreted as asthma or chronic bronchitis. MATERIAL AND METHODS: To assess
      the value of lung function tests for differential diagnosis we used these tests
      in 33 patients with upper airway obstruction caused by an enlargement of the
      thyroid gland. The clinical examination consisted of an evaluation of the
      respiration, examination of the movement of the vocal chords, thyroid parameters,
      Tc scintigraphy, ultrasound examination, and X-ray examination of the thorax and
      trachea up to the level of the glottis, supplemented by a CT scan if needed. Lung
      function tests were carried out in all patients before and after the operation as
      conventional spirometry with registration of the flow-volume curve and
      application of peak expiratory flow (PEF), maximal expiratory and inspiratory
      flow at 50% of the vital capacity (MEF 50 and MIF 50) and MEF 50/MIF 50. RESULTS:
      The surgical treatment consisted in hemithyroidectomy in 10 patients and total
      thyroidectomy in 23 patients. In all cases, considerable clinical improvement in
      respiration was achieved and the X-ray examination showed a normalisation of the
      lumen of the trachea. In 24 of 33 patients (73%), the flow-volume curve showed
      preoperatively a configuration compatible with a variable upper airway
      obstruction (i.e. MIF 50 < MEF 50). An increase postoperatively was found in the
      PEF of 21 patients (64%) and MEF 50/MIF 50 < 1 in 19 patients (58%). DISCUSSION:
      It is important to distinguish between respiratory symptoms (stridor) caused by
      obstruction of the upper air way and dyspnoea in cardiopulmonary diseases. Lung
      function tests with registration of the flow-volume curve and measurement of MEF,
      MIF, and PEF are a useful supplement, as values indicating upper airway
      obstruction will be present in about 60% of the cases. Lung function tests pre-
      and postoperatively will serve as a good control on the effect of the operation
      on the thyroid gland.

PMID- 11985003
TI  - [Malaria in the county of Funen 1987-1999].
AB  - INTRODUCTION: We describe epidemiological, prophylactic, and clinical aspects of
      imported malaria in the county of Funen, 1987-1999. MATERIAL AND METHODS: The
      medical records of 136 patients were reviewed for age, gender, nationality, place
      of exposure, chemoprophylaxis, time lag from departure to diagnosis, Plasmodium
      species, treatment, and complications. Data on prescribed chemoprophylaxis
      dispensed from the pharmacies in the county of Funen were recorded. RESULTS:
      Seventy-two per cent of the patients were Danish, 28% foreigners. Sixty per cent
      of the cases were caused by P. falciparum, of more than 90% which was acquired in
      sub-Saharan Africa. Cases of benign malaria were most often acquired in SE Asia.
      In the 49 patients with falciparum malaria, who had taken chemoprophylaxis, only
      31 (63%) were fully compliant. Compliance was 76% in patients taking chloroquine
      phosphate + proguanil and 36% in patients taking only chloroquine phosphate. Six
      patients had complications, but all recovered. DISCUSSION: Contributory causes in
      a large number of the reported cases of imported malaria in this study were no
      chemoprophylaxis or poor compliance. With respect to falciparum malaria,
      prescription of non-recommended chemoprophylaxis also contributed.
      Chemoprophylaxis dispensed from the pharmacies on Funen over recent years
      indicates that general practitioners are aware of altered recommendations.

PMID- 11985004
TI  - [Testicular microlithiasis--are biopsy and follow-up necessary?].
AB  - INTRODUCTION: Improvement in the technology of ultrasound has made it possible to
      visualise small calcifications in the testes, known in the literature as
      testicular microlithiasis (TM). TM is described in otherwise healthy men, but is
      also found related to cancer and CIS. Here we will discuss the evaluation and
      follow up of patients with diagnosed TM. MATERIAL AND METHODS: The study
      comprises 14 patients in whom TM was diagnosed sonographically in the period from
      December 1997 to May 2000. RESULTS: Ultrasound indicated cancer in two patients.
      Pathology showed germ cell cancer in both. In 12 patients, ultrasound showed only
      TM, no suspicion of cancer. Biopsies taken in eight of these patients were all
      benign. DISCUSSION: The prevalence of TM is still unknown, as is its aetiology.
      TM is somehow correlated to testicular cancer, as microliths are found much more
      often in testes with cancer than in those without malignancy. However, in the
      vast majority of patients, evidence of cancer or CIS cannot be found. Development
      of cancer in patients formerly diagnosed with TM is rarely described. In the case
      of TM and no sonographic signs of cancer, we therefore believe biopsies can be
      limited to patients at increased risk of testicular cancer, for instance those
      with retained or small atrophic testes, and also possibly to patients known to
      have developed TM between repeated ultrasound examinations. If a biopsy shows no
      signs of malignancy or CIS, we see no need for follow up. If biopsy is not
      indicated, we recommend a clinical check up, followed by further investigations
      if these are indicated.

PMID- 11985005
TI  - [Asystole following synchronized DC conversion].
AB  - A case of asystole following direct current CDC cardioversion for atrial
      fibrillation is described and studies of the complications associated with DC
      cardioversion are presented. It is important to be aware of the possible severe
      complications of DC cardioversion.

PMID- 11985006
TI  - [Watermelon stomach and scleroderma].
AB  - We report here a 72-year-old man with severe, persistent, iron deficiency
      anaemia. Upper gastrointestinal endoscopy revealed red stripes radiating to the
      pylorus, characteristic of watermelon stomach (gastric antral vascular ectasia).
      The patient was found to have scleroderma with calcinosis, sclerodactyly, and
      telangiectasias, but neither Raynaud's phenomenon nor oesophageal dysmotility.
      The patient was treated with endoscopic Argon laser therapy, repeated six times,
      but this did not control the bleeding. Altogether the patient received 62 units
      of blood transfusions. The patient died after 9 months.

PMID- 11985007
TI  - [Radiation myelopathy. Four case reports].
AB  - Chronically progressive (permanent) radiation myelopathy is a serious
      complication to irradiation of head/neck carcinoma. We describe four patients who
      developed stationary neurological deficits with a considerable reduction in
      function. One patient received a radiation dose below 50 Gy and the others up to
      58 Gy against the cervical medulla. One patient developed an intramedullary
      syrinx.

PMID- 11985008
TI  - [Recommendations from the Danish Society of Plastic and Reconstructive Surgery
      and its quality assurance committee].

PMID- 11985009
TI  - [Treatment of ascites without laparocentesis].

PMID- 11985010
TI  - [Poisoning after decantation].

PMID- 11985011
TI  - [Animal experiments are necessary. Coordinated control functions are difficult to
      study without the use of nature's most complex systems: mammals and human
      beings].

PMID- 11985012
TI  - [Home care aides should be competent in health care. Changed guidelines when it
      comes to drug handling].

PMID- 11985013
TI  - [Unqualified home care aides put the patient at risk. Better knowledge concerning
      drug administration must be required].
AB  - During the last few years the home care services have had to face an increased
      responsibility for medical tasks. A study in the city of Malmo in 1993, repeated
      in 1998, shows that 95% of the health care assistants are engaged in the
      administration of medication. The studies demonstrate that health care assistants
      have inadequate knowledge not only about medicines and their administration but
      also about common diseases and their symptoms. Delegating the task of medication
      administration to non-nurse personnel within the social services therefore
      entails an increased risk for the patient.

PMID- 11985014
TI  - [Nuclear receptors in man, fly and worm provide greater understanding of
      disease].
AB  - Recently the complete genomic sequences for three very different multicellular
      organisms have been published, from one nematode (Caenorhabditis elegans), one
      fly (Drosophila melanogaster) and human (Homo sapiens). Of course, this means a
      breakthrough in many ways for biological research. Summarised in this article are
      the findings made using these genomic sequences regarding the protein family of
      nuclear receptors. This is a group of transcription factors involved in many
      important biological processes, i.e. regulation of cholesterol homeostasis and
      fertility; classical members of this protein family are, amongst others, the
      receptors for estradiol and progesterone.

PMID- 11985015
TI  - [Newly discovered association between lung disease and surfactant proteins].

PMID- 11985016
TI  - [High sense of coherence can have health enhancing effects].
AB  - Sense of coherence (SOC), e.g. meaningfulness of life, is according to the
      sociologist A. Antonovsky a health-promoting construct, which has been used in a
      number of descriptive studies in various populations. The aim of this population
      based cross-sectional study was to investigate if middle-aged women with a self
      reported low level of SOC also differed in biological variables, e.g. related to
      glucose and lipid metabolism, from women with a high level of SOC. These
      variables could potentially represent links in the pathophysiological chain of
      events causing somatic disease. We found significant differences according to
      dyslipidaemia (low HDL cholesterol and increased triglyceride levels) between
      groups of women with differing SOC scores, most negative findings were found in
      the group with lowest SOC. Women with medium-high or high SOC also reported less
      symptoms and need of regular medical controls. The results support a potential
      association between cognitive processes (SOC) and biological mechanisms causing
      adverse health effects.

PMID- 11985017
TI  - [Linezolide--an antibiotic with new action mechanism].

PMID- 11985018
TI  - [Low birth weight and social factors affect the risk of coronary disease].

PMID- 11985019
TI  - [The Helsinki Declaration. A broader basis concerning the next revision is
      wanted].

PMID- 11985020
TI  - [Our ethical obligation is to allow animal experiments!].

PMID- 11985021
TI  - [A new place for the mentally ill--patients in Beckomberga during the 1930s].

PMID- 11985022
TI  - [Till death do them part?].

PMID- 11985023
TI  - [A proposal on ethical scrutiny of research has a legal lopsidedness and should
      be reconsidered].

PMID- 11985024
TI  - [Realization of national programs via "green islands" and smart family practice
      listing].

PMID- 11985025
TI  - [Compulsory specialist examination?].

PMID- 11985026
TI  - [Somatization--a challenge for health care].

PMID- 11985027
TI  - ["NSAID preparations prevent Alzheimer disease"--a treacherous headline!].

PMID- 11985028
TI  - [SOS-International should revise own routines].

PMID- 11985029
TI  - [It's ageism to deprive retired physicians of the right to prescribe drugs at
      reduced rate].

PMID- 11985030
TI  - [Three level course and internship certificates].

PMID- 11985031
TI  - Violations of the WHO code for ethical marketing of baby milks.

PMID- 11985033
TI  - Grieving and surviving PPS.

PMID- 11985032
TI  - Policy makers will hear from you!

PMID- 11985034
TI  - PPS case mix methodology.

PMID- 11985035
TI  - Needlesticks.

PMID- 11985036
TI  - 2001-2002 Joint Commission Home Care Manual: what's new? Part 1.
AB  - The changes in the format of the 2001-2002 CAMHC are tremendously helpful for
      organizations that provide multiple types of home care programs. At last,
      reviewing the common and service-specific standards can identify the applicable
      standards. The most significant change is the change in the aggregation
      methodology that places home care and hospice organizations at higher risk for
      type 1 recommendation(s). The next Accreditation Strategies column will review
      the changes in the standards in the 2001-2002 CAMHC from the chapter entitled
      "Improving Organizational Performance" through the chapter entitled
      "Surveillance, Prevention and Control of Infection".

PMID- 11985037
TI  - Using performance improvement to reinvent your skin care program.

PMID- 11985038
TI  - Case management is critical in PPS.
AB  - The home care industry is undergoing tremendous changes in the reimbursement
      model presented in the Prospective Payment System (PPS). Case management is a
      model of care delivery that can provide the oversight required in this
      comprehensive prospective payment environment.

PMID- 11985039
TI  - Hospice outcomes: meeting requirements and developing a national consensus.
AB  - This article describes the rationale for outcome measurement in hospice care and
      the requirements related to such measurement as stipulated by regulatory bodies,
      third party payers, and accreditation organizations. Also discussed are the end
      result outcomes of hospice care and efforts by the National Hospice and
      Palliative Care Organization to develop consensus related to definition and
      measurement of these outcomes.

PMID- 11985040
TI  - Rehospitalization among home healthcare patients: results of a prospective study.
AB  - Reduction in rehospitalization is an outcome measure used to evaluate home care
      services, especially in Outcome Based Quality Management using OASIS data;
      however, practitioners and managers must carefully analyze the reasons patients
      return to the hospital. This study examines events leading to rehospitalization
      of patients with CHF, whether it is possible to determine upon admission which
      patients are at risk, and whether the readmissions were necessary and/or
      preventable. Among the study's important findings are that half of the patients
      developed a new problem that required the rehospitalization. This and other
      research outcomes should be considered when analyzing adverse event reports.

PMID- 11985041
TI  - Clinical update: deep vein thrombosis.

PMID- 11985042
TI  - Updated definition of homebound status.

PMID- 11985043
TI  - About the cardiac home care nursing practice guidelines.

PMID- 11985044
TI  - Telehealth interventions for PPS.
AB  - The ongoing challenge for nurses using home telehealth in PPS will be defining
      and routinely redefining what works to help patients better manage themselves and
      their treatment and care routines. This process requires careful thought and
      customization of telehealth routines and interventions. In PPS there is clearly a
      demand that nurses document that patients have followed needed care directives to
      reach successful outcomes, whether or not they have followed a conventional
      telehealth path to get there.

PMID- 11985047
TI  - [Disturbance of lipid metabolism].
AB  - The disturbance of lipid metabolism is seen in some inherited diseases and also
      in patients with some kinds of underlying diseases. The presence of its
      disturbance can be detected by measuring the concentrations of cholesterol and
      triglyceride in serum. Although hyperlipidemia or hypolipidemia is the result of
      abnormal lipid metabolism, hyperlipidemia is of more concern to physicians
      because of the close association with atherosclerosis. Responsible genes for some
      primary (or hereditary) hyperlipidemic diseases have been confirmed as follows;
      LPL or apo C-II for primary chylomicronemia, LDL receptor for familial
      hypercholesterolemia and apo B-100 for familial defective apo B-100. However, the
      responsible gene remains controversial for familial combined hyperlipidemia,
      though AI/CIII/AIV cluster is one of the possible candidate genes. Secondary
      hyperlipidemia is caused by various diseases such as diabetes mellitus, renal
      diseases and cholestasis. This type of hyperlipidemia is improved by therapy for
      the underlying diseases. To date, the mechanism of lipid metabolism has been
      defined in a molecular basis. In fact, sterol regulatory element-binding protein
      (SREBP), peroxisome proliferator-activated receptor (PPAR) and ATP-binding
      cassette transporter subfamily A, member 1(ABCA1) were recently identified and it
      was demonstrated that these regulate lipid metabolism.

PMID- 11985048
TI  - [Development of homogeneous assay for HDL-C in serum].
AB  - Recent development of several homogeneous assays for measuring HDL-cholesterol
      (HDL-C) in serum without pretreatment has been reviewed. Several problems on the
      five homogeneous assays based on PEG-modified enzyme/alpha-cyclodextrin sulfate
      (PEGME), polyanion-polymer/detergent (PPD), immunoinhibition, catalase/detergent
      and 4-sulfonyl calyx[8]areine are discussed comparing with CDC reference method.
      The two homogeneous assays (PEGME and PPD) used in many laboratories were precise
      and correlated well with CDC reference method (mean percentage bias: < 5%). The
      discrepancies of recoveries for apo E-rich HDL-C were observed among reagents of
      homogeneous assays in serum from patients with hepatobiliary diseases and
      cholesterol ester transfer protein (CETP) deficiency. Apo E-rich HDL slightly
      contained in normal serum was most recovered by homogeneous methods, but not by
      precipitation methods. The differences between the normal values for HDL-C
      obtained by homogeneous assay (PEGME method) and precipitation method (dextran
      sulfate-phosphotungstate-MgCl2) were statistically significant (p < 0.01).

PMID- 11985049
TI  - [A new comparison method of HDL-cholesterol measurement for evaluation of routine
      methods].

PMID- 11985050
TI  - [Evaluation of LDL-cholesterol measurement].
AB  - As a result of increased recognition of elevated LDL-cholesterol (LDL-C) as a
      risk for ischemic heart disease, the necessity for LDL-C measurement emerged in
      clinical laboratories. Consequently various LDL-C measurement methods were
      developed. The objective of the present review article is to compare and to
      evaluate the characteristics of various methods for LDL-C measurement. Because
      LDL is a particle defined by its density, ultracentrifugation method; beta
      quantification is currently considered the reference method, but it is a time
      consuming and expensive technique. The evaluation by Friedewald's equation is
      simple and applicable to the vast majority of normolipidemic samples. LDL-C
      measurement by electrophoresis provides an evaluation of LDL along with other
      lipoproteins. Homogeneous assays have the advantage of obviating the need for
      pretreatment of samples, and this is suitable for online performance, requiring
      only a few microliters of sample. Generally, there is little disagreement between
      methods in LDL-C data of normolipidemic samples. However, when the sample is from
      patients with dyslipidemia, there may be disagreement in LDL-C results between
      methods and the reason for this phenomena has been discussed. At the moment, the
      method for LDL-C measurement at each clinical laboratory has to be selected by
      adequately balancing demands, costs and benefits.

PMID- 11985051
TI  - [Oxidized LDL, clinical aspects and measurement methods].
AB  - It is well recognized that oxidative modification of low-density lipoprotein(LDL)
      accelerates atherogenesis of the arterial vascular wall. Each of lipid
      peroxidation products, surface charge, or spectrophotometric patterns is
      applicable to the evaluation of in vitro oxidation. The lag time may contribute
      to the evaluation of effect of the lipid lowering and antioxidant drugs. ELISA
      using monoclonal antibody has the potential for clinical use. However, the
      applicability is not yet established, because of the different kinds of antibody
      used.

PMID- 11985052
TI  - [Treatment of hyperlipidemia].
AB  - Hyperlipidemia, especially hypercholesterolemia is one of the most important risk
      factors for coronary heart disease. Now it is well recognized that aggressive
      lipid-lowering drug treatment in high-risk individuals reduces coronary heart
      disease morbidity and mortality rates and increases overall survival.
      Hypertriglyceridemia has now been recognized as another important risk factor for
      coronary heart disease. Recently, much attention has been focused on the
      atherogenesis of small, dense LDL, remnant lipoprotein and isolated
      hypoalphalipoproteinemia. Hypertriglyceridemia is known to be deeply involved in
      the pathogenesis of all of these abnormal lipoprotein profiles. Therefore,
      treatment of hypertriglyceridemia as well as hypercholesterolemia must be fully
      discussed. In this issue, I will talk about new insights into treatment of
      dyslipidemia by changing the life style and/or by various hypolipidemic drugs.

PMID- 11985053
TI  - [Choosing effective laboratory tests for hyperlipidemia, and the reimbursement
      system].
AB  - The Japanese Government has developed health-care payment policies designed to
      balance the growth of health-care expenditure against other national priorities.
      Often these policies tend to limit the various services. The Japan
      Atherosclerosis Society published management guidelines for hyperlipidemia in
      1997. There is increasing concern about the cost of laboratory studies as well as
      the cost of the management of hyperlipidemia. The Japanese Society of Laboratory
      Medicine has also developed standards to choose effective laboratory tests for
      general practitioners. Health professionals must have a clear knowledge of not
      only the clinical significance of the laboratory tests but also of the
      reimbursement system in order to understand the economic factors that control the
      services available to their patients. Both knowledge can make the physicians
      proper medical services for the patients.

PMID- 11985054
TI  - [How is bone formed and resorbed?-- molecular mechanisms of bone formation and
      resorption].
AB  - Bone has developed as a storage of calcium as well as a supporting tissue in
      vertebrates. Bone is a complex tissue in which resorption and formation take
      place throughout life. This process is called bone remodeling. Osteotrophic
      hormones such as 1 alpha,25-dihydroxyvitamin D3[1 alpha,25 (OH) 2D3], parathyroid
      hormone (PTH) and calcitonin maintain serum calcium homeostasis within a narrow
      range of 9 to 10 mg/dl by regulating intestinal absorption of calcium and bone
      remodeling. Bone tissue contains various types of cells, of which bone-forming
      osteoblasts and bone-resorbing osteoclasts are mainly responsible for bone
      remodeling. Osteoblasts arise from common progenitors with chondrocytes, myotubes
      and adipocytes. Recently, four research groups independently identified core
      binding protein alpha-1(Cbfa-1) as a key transcription factor for osteoblast
      differentiation and bone formation, since Cbaf-1 knockout mice completely lacked
      bone formation due to maturation arrest of osteoblasts. In contrast,
      multinucleated osteoclasts are primarily responsible for bone resorption. The
      recent discovery of new members of tumor necroses factor (TNF) receptor-ligand
      family has indicated the precise mechanism by which osteoblasts/stromal cells
      regulate osteoclast formation. Osteoblasts/stromal cells express a new member of
      the TNF ligand family "osteoclast differentiation factor (ODF)" as a membrane
      associated factor. Osteoclast progenitors which express ODF receptor(RANK)
      recognize ODF through cell-to-cell interaction with osteoblasts/stromal cells,
      then differentiate into osteoclats. Osteoprotegerin (OPG)/osteoclastogenesis
      inhibitory factor (OCIF) is a soluble decoy receptor for ODF. Thus, ODF, RANK and
      OPG/OCIF are the three key molecules for osteoclast formation. The discovery of
      Cbfa-1 and ODF may establish a new way to treat several metabolic bone diseases
      caused by abnormal bone formation and resorption.

PMID- 11985055
TI  - [Criteria for diagnosing DIC].
AB  - The differences between reagents of prothrombin time (PT), fibrinogen and fibrin
      and fibrinogen degradation products(FDP) were examined in patients with
      disseminated intravascular coagulation (DIC) and without DIC. The sensitivity of
      the PT ratio for DIC is lowered by the PT reagent with a high international
      sensitivity index, and the difference between PT reagents was marked. The
      sensitivity of PT-international normalized ratio (INR) for DIC was higher than
      that of the PT ratio and the difference between reagents in PT-INR was low.
      Though the difference between reagents for fibrinogen is slight, the usefulness
      in diagnosing DIC is also slight. Though the sensitivity of FDP for DIC was good,
      the difference between FDP reagents was marked. Therefore, standardization of PT
      and FDP seems to be necessary. Concordance of overt-DIC diagnostic criteria by
      the International Society of Thrombosis and Haemostasis (ISTH) and DIC diagnostic
      criteria of Japanese Ministry of Health and Welfare (JMHW) was about 70%, and
      overt-DIC diagnostic criteria of ISTH seemed to diagnose the typical type of DIC
      diagnosed by JMHW criteria. Finally, the diagnostic criteria of non-overt DIC are
      expected to become increasingly important.

PMID- 11985056
TI  - [Prothrombin time and its standardization: a potentiality to introduce INR method
      in criteria for disseminated intravascular coagulation].
AB  - Prothrombin time (PT) is widely utilized for evaluation of diseases with single
      or multiple coagulation factors disorders, such as severe liver dysfunction and
      disseminated intravascular coagulation (DIC). However, its standardization of
      reagent and method is not established yet for universal purpose except
      International Normalized Ratio (INR) for control of oral anticoagulant therapy
      (OAT). Neither Prothrombin time ratio adapted in Japanese criteria for DIC nor
      seconds method in criteria reported by the last SSC meeting is corrected between
      assays, therefore much dependence on these criteria causes risk of misdiagnosis.
      In order to resolve incoherence of method of PT, we performed this study for
      introducing INR method to diagnostic criteria for DIC. In our results,
      sensitivities of two reagents from human tissue factor (TF) to DIC model plasma
      with middle to low activities of multiple coagulation factors almost equal to
      plasma from patients with OAC, although other two reagents from rabbit TF show
      discrepancy of sensitivities between DIC and OAT plasma. These suggest a
      potentiality to introduce INR system to diagnosis of DIC when human TF is used as
      a PT reagent. Based on standardization of method, significance of PT in DIC
      criteria should be reevaluated in worldwide.

PMID- 11985057
TI  - [Standardization of the laboratory method for antithrombin activity measurement].
AB  - Measurement of antithrombin (AT) activity in plasma provides important
      information for the diagnosis of congential antithrombin deficiency and
      disseminated intravascular coagulation. When measured in the presence of heparin,
      plasma antithrombin activity includes heparin cofactor II activity as about 20
      30% of the total activity. Antithrombin assay methods measuring plasma anti-F.Xa
      activity or those measured in the presence of 0.22 M NaCl exclude the influence
      of HC II activity. Dilution of the plasma sample is necessary to measure the
      heparin cofactor anti-thrombin activity of AT correctly. A laboratory method that
      precisely reflects plasma heparin cofactor anti-thrombin activity of AT should be
      established as the standard laboratory method.

PMID- 11985059
TI  - [Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic
      liver cirrhosis].
AB  - We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver
      cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake
      of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed
      histologically. Infections with hepatitis B and C viruses were ruled out by
      assaying serum virus markers. No tumor was detected in liver by ultrasonography
      and computed tomography during observation period. None of the patients studied
      were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with
      alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast,
      only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had
      elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of
      hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic
      liver cirrhosis approached its rates in HCC. However, the time course for the
      elevation of serum PIVKA-II levels was different each other in alcoholic liver
      cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until
      therapy. In contrast, its elevation was transient and its levels returned to
      baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and
      ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver
      cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II
      levels in patients with alcoholic liver cirrhosis occurred, we studied the effect
      of vitamin K on production of PIVKA-II and AFP by hepatocytes.
      Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of
      various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no
      effect on AFP production. In contrast, PIVKA-II production was inhibited by
      addition of vitamin K in a dose dependent manner. Moreover, elevation of serum
      PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by
      administration of vitamin K (Kaytwo) to these patients. Taken together, these
      results suggest that vitamin K may have a role in the mechanism of PIVKA-II
      elevation in sera of these patients. Then, we measured serum concentrations of
      vitamin K(PK, MK-4, MK-7) in these patients. There was no correlation observed
      between vitamin K and PIVKA-II in these patients. This result suggests that
      elevation of serum PIVKA-II in these patients may not be due to vitamin K
      deficiency. One question not answered here is how serum PIVKA-II levels in these
      patients are suppressed by treatment with vitamin K (Kaytwo). More detailed
      analysis of the mechanism of elevation of serum PIVKA-II levels in patients with
      alcoholic liver cirrhosis is needed.

PMID- 11985060
TI  - [Study of genotype frequencies of ANP 664G/A polymorphism in normal subjects and
      CVD patients, and its association with plasma ANP levels].
AB  - Atrial natriuretic peptide (ANP) plays a crucial role in regulating body fluid
      volume and blood pressure, by promoting natriuresis and vasodilatation and by
      inhibiting the renin-angiotensin system. Plasma levels of ANP are elevated in
      heart failure and hypertension, and ANP is thus believed to be involved in the
      pathogenesis of cardiovascular disorders. Previous case-control studies have
      shown that a single nucleotide polymorphism in the first exon of ANP gene,
      664G/A, is associated with a risk of cerebrovascular disease (CVD) in white
      populations. Plasma ANP levels, however, were not evaluated in these studies in
      relation to the 664G/A, although the nucleotide substitution causes an amino-acid
      change in the propeptide of ANP. In this study, we analyzed the genotype
      frequencies of the 664G/A in Japanese patients with CVD (n = 199) and age- and
      gender-matched control subjects(n = 176). Genotypes with the 664A allele in the
      Japanese control subjects (G/A and A/A 12.5%) were apparently more frequent
      compared to the published frequency of the white control population (G/A and A/A
      6.6%, p = 0.0437). Genotypes with the 664A allele, however, were not
      significantly different between our CVD patients(15.1%) and controls (12.5% p =
      0.4714). In the control group (n = 137), the mean plasma ANP levels were not
      different between the 664G/G (15.7 +/- 10.7 pg/ml) and 664G/A genotypes (15.6 +/-
      6.8 pg/ml, p = 0.9708). These results suggest that there is a racial difference
      in the allele frequency of 664G/A, and that this polymorphism may not be a major
      risk factor for CVD in the Japanese, nor is it a major determinant of plasma ANP
      level.

PMID- 11985061
TI  - [Von Willebrand factor-cleaving protease activity in patients of collagen disease
      with antiphospholipid antibodies].
AB  - Acquired thrombotic thrombocytopenic purpura (TTP), characterized by widespread
      thrombus formation in the microcirculation, is a ponderous complication of
      antiphospholipid syndrome. Recently, von Willebrand factor-cleaving protease (VWF
      CPase) activity has been reported as a possible determinant for the occurrence of
      TTP. To clarify the role of VWF-CPase in the thrombus formation associated with
      antiphospholipid syndrome, we investigated plasma VWF-CPase activity in patients
      of collagen diseases with lupus anticoagulant (LA). Decreased plasma VWF-CPase
      activity less than 50% of the normal activity was observed in 25.7% (n = 18) in
      70 patients with collagen diseases and 7 (10%) cases of them showed more lower
      VWF-CPase activity less than 25%. The IgG fractions obtained from 2 patients with
      the low VWF-CPase activity strongly inhibited the proteolytic reaction of normal
      VWF-CPase. There was no significant relationship between LA and plasma VWF-CPase
      activity. Thrombotic episodes, especially arterial thrombosis, were more
      frequently observed in LA-positive patients with low VWF-CPase activity. These
      results suggest that decreased activity of VWF-CPase, partly due to IgG type
      inhibitor to the enzyme activity may be an additional risk factor for arterial
      thrombosis in collagen disease patients with antiphospholipid antibodies.

PMID- 11985062
TI  - [Determination of medullasin levels for the diagnosis of multiple sclerosis].
AB  - Medullasin levels in granulocytes of patients with neurological diseases and
      healthy volunteers were determined by the enzyme immunoassay using mouse
      monoclonal antibodies against human medullasin and o-phenylenediamine-H2O2 as the
      detection system of the enzyme activity. One hundred twenty-one out of 159
      patients with multiple sclerosis (76.1%) showed positive results (above means of
      normals + 2SD) in this test, while only 16.9% (24/142) of patients with non
      inflammatory neurological diseases had positive results. This enzyme immunoassay
      method for medullasin is considered to be an useful paraclinical test for the
      diagnosis of multiple sclerosis.

PMID- 11985063
TI  - [Re-evaluation of HCV Ab detection kits approved for marketing in Japan].

PMID- 11985064
TI  - [Trends in recent studies of memory by cognitive neuroscience approach].

PMID- 11985065
TI  - [Cognitive process of time perception and working memory].

PMID- 11985066
TI  - [Time-space characteristics in cognition of facial expressions and eye contact:
      Psychological basis in communication].

PMID- 11985067
TI  - [Search for the mechanism of cognition development].

PMID- 11985068
TI  - [Psychiatric symptoms and pathological processes in patients with Alzheimer's
      disease--special reference to dissection analysis of the visual-spatial world].

PMID- 11985069
TI  - [Effects of anti-psychotic agents on brain glucose metabolism and regional
      cerebral circulation in patients with schizophrenia-- study by functional brain
      imaging of SPECT and PET].

PMID- 11985070
TI  - [Establishment of the Systematic Brain Bank Network for studies of mental
      disorders].

PMID- 11985071
TI  - [Questionnaire survey on the utilization of forensic psychiatric evidence in
      criminal proceedings].

PMID- 11985072
TI  - [Practice guidelines for cardiopulmonary resuscitation].

PMID- 11985073
TI  - [Two cases of broncholithiasis].

PMID- 11985074
TI  - [Pseudoaneurysm of the thoracoabdominal aorta from colonic injury by the anterior
      fixation device].

PMID- 11985075
TI  - [Slowly progressive type 1 diabetes mellitus whose anti-GAD antibody showed
      positive conversion after 9 years interval from the onset of the disease].

PMID- 11985076
TI  - [Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome
      with malignant lymphoma].

PMID- 11985077
TI  - [Economy class syndrome associated with electrocardiographic changes that
      required discrimination from coronary artery disease].

PMID- 11985078
TI  - [Combined antithymocyte globulin. cyclosporin. methylprednisolone and granulocyte
      colony-stimulating factor are effective in a patient with hepatitis-associated
      severe aplastic anemia].

PMID- 11985079
TI  - [History of cardiology in the last 100 years: Heart auscultation].

PMID- 11985080
TI  - [History of cardiology in the last 100 years: ECG].

PMID- 11985081
TI  - [History of cardiology in the last 100 years: Cardiac electrophysiological
      studies].

PMID- 11985082
TI  - [History of cardiology in the last 100 years: Cardiac catheterization].

PMID- 11985083
TI  - [History of cardiology in the past 100 years: CT Xray and MRI].

PMID- 11985084
TI  - [History of cardiology in the last 100 years: Echocardiography].

PMID- 11985085
TI  - [History of cardiology in the last 100 years: Heart nuclear medicine].

PMID- 11985086
TI  - [History of cardiology in the last 100 years: Heart and vasoactive substances].

PMID- 11985087
TI  - [History of cardiology in the last 100 years: Genetic studies of cardiovascular
      diseases].

PMID- 11985088
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      Kawasaki disease].

PMID- 11985089
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      atrioventricular node (Tawara)].

PMID- 11985090
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      percutaneous transvenous mitral commissurotomy, PTMC].

PMID- 11985091
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      Tako-tsubo like left ventricular dysfunction].

PMID- 11985092
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      apical hypertrophy].

PMID- 11985093
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      coronary vasospasm].

PMID- 11985094
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      Fabry's disease].

PMID- 11985095
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      Emax].

PMID- 11985096
TI  - [History of cardiology in the last 100 years: Japanese contribution to studies on
      ATP sensitive potassium channel].

PMID- 11985097
TI  - [History of cardiology in the last 100 years: Angina pectoris].

PMID- 11985098
TI  - [History of cardiology in the last 100 years: Myocardial infarction].

PMID- 11985099
TI  - [History of cardiology in the last 100 years: Heart failure].

PMID- 11985100
TI  - [History of cardiology in the last 100 years: Cardiomyopathies].

PMID- 11985101
TI  - [History of cardiology in the last 100 years: Heart valve diseases].

PMID- 11985102
TI  - [History of cardiology in the last 100 years: Pediatric cardiology].

PMID- 11985103
TI  - [History of cardiology in the last 100 years: Endocarditis].

PMID- 11985104
TI  - [History of cardiology in the last 100 years: Arrhythmia].

PMID- 11985105
TI  - [History of cardiology in the last 100 years: Cor pulmonale].

PMID- 11985106
TI  - [History of cardiology in the last 100 years: Aortic aneurysm and
      arteriosclerosis obliterans].

PMID- 11985107
TI  - [History of cardiology in the last 100 years: Pulmonary thromboembolism].

PMID- 11985108
TI  - [History of cardiology in the last 100 years: Hypertension].

PMID- 11985109
TI  - [History of cardiology in the 20th century and outlook for cardiology in the 21st
      century(discussion)].

PMID- 11985110
TI  - [Practice guidelines for therapy of patients with hypertension].

PMID- 11985111
TI  - [Practice guidelines for patients with chronic heart failure].

PMID- 11985112
TI  - [Practice guidelines for therapy of patients with ischemic heart disease].

PMID- 11985113
TI  - [Basic and clinical studies on methampetamine-related psychosis].

PMID- 11985114
TI  - [Biological studies on alcoholism and their application in clinical practice].

PMID- 11985115
TI  - [Role of rehabilitation in university hospital psychiatric departments].

PMID- 11985116
TI  - [Imaginary companion in adolescence].
AB  - The phenomenon of imaginary companions, which is usually regarded as normal in
      children, but which when encountered in adolescence suggests a psychopathologic
      condition, appears to have had limited investigation. This study indicates some
      psychopathologic characteristics of imaginary companions by interviewing
      adolescent patients. Imaginary companions are experienced as one or more
      invisible persons who have some conversations with patients directly and mutually
      for a period of time. They consist of vivid images which range between pure
      perceptions and pure images. The position of these images is not specified, and
      includes images perceived internally and externally by the patient. Adolescent
      patients sense the reality of these images and think of them as other persons,
      but recognize that these are not real people. Generally, imaginary companions are
      beneficial to the patients. These characteristics indicate that the phenomenon of
      imaginary companions has a mainly pathologic structure, but some characteristics,
      such as the patients' recognition of the imaginary aspect of the companion and
      the benefit for patients, does not fall under the category of psychopathology. We
      suppose that elucidation of this phenomenon would lead us to productive research
      in the psychopathologic field.

PMID- 11985117
TI  - [Role of psychiatrists in capital punishment cases : a review].
AB  - Many medical organizations have passed resolutions banning participation of
      psychiatrists in legal executions, such as the Madrid Declaration of World
      Psychiatric Association. The Criminal Procedure Act of Japan prohibits the
      execution of the insane. Although the USA and Japan are both among the few so
      called developed countries that have a system of capital punishment, many
      disputes about psychiatrists' participation in death penalty cases have occurred
      in the US, but few in Japan. This author has reviewed papers addressing this
      issue. The U.S. Supreme Court decided in Ford v. Wainwright that the execution of
      an "insane" inmate was not constitutional. The rationale for excluding the
      mentally incompetent from execution, however, is not completely clear. The most
      compelling reason is that execution does not satisfy the requirement for
      "effective retribution," since the insane criminal is not capable of
      understanding the implications of the death penalty. Nonetheless, there are those
      who dispute this interpretation and offer other explanations. Psychiatrists may
      be called upon to assess a criminal's competency for execution. Some find no
      problem with this practice, while others object to it stating that it conflicts
      with the ethical tenet to "first do no harm." Those who argue from a middle
      position insist on assessing competency while recognizing the existence of
      problems in making such an assessment. Furthermore, there is controversy over
      which factors exactly constitutes "competency to be executed." Usually, it is
      thought to be one's capacity to understand the nature of the death penalty and
      the reasons why the penalty is to be inflicted, but other arguments exist,
      including the capacity to assist legal counsel in last minute appeals. The
      question of whether to offer treatment to death row inmates who have been found
      incompetent to be executed is also under debate. The first position argues that
      they should "never be treated", because such prisoners would be executed when
      treatment restores competency. The second, always-treat-position, asserts that
      psychiatrists are responsible for treating severe mental illness whenever
      possible. The third, intermediate position, insists upon treatment with several
      conditions, which entail, for example, respecting the prisoner's autonomy and/or
      selecting forms of treatment that are unlikely to restore competency. When
      treatment is given, assessment as to whether competency has been restored is then
      required. This is still a troublesome issue. The decision in Perry v. Louisiana
      dealt with the question of whether the state may forcibly treat prisoners
      incompetent for execution. There were reports about ambivalence and anger among
      the staff of a psychiatric hospital where an inmate found incompetent for
      execution was treated. More than a few disputes insist that the ethical dilemma
      can only be resolved by commuting the sentences of incompetent death row
      prisoners to life imprisonment. This author further asserts that the
      secretiveness with which the Ministry of Justice of Japan handles these types of
      cases should be abolished as soon as possible.

PMID- 11985118
TI  - Polymerase chain reaction in diagnosis of Borrelia burgdorferi infections and
      studies on taxonomic classification.
AB  - Lyme borreliosis caused by the spirochete Borrelia burgdorferi is now the most
      common vectorborne disease in North America, Europe and Asia. It is a
      multisystemic infection which may cause skin, neurological, cardiac or
      rheumatologic disorders. The aims of the present thesis were: (i) to develop a
      PCR assay for direct detection of B. burgdorferi DNA and to evaluate the
      diagnostic utility of PCR in clinical specimens from patients with Lyme
      borreliosis and (ii) to study the taxonomic classification of B. burgdorferi
      isolates and its implications for epidemiology and clinical presentation.
      Laboratory diagnosis of Lyme borreliosis by direct demonstration of B.
      burgdorferi in clinical specimens would compared to current serology allow (i)
      optimal specificity, (ii) increased sensitivity during the first weeks of
      infection, when the antibody response is not yet detectable and (iii)
      discrimination between ongoing and past infection. Due to the extreme paucity of
      spirochetes in clinical specimens neither in vitro culture nor antigen detection
      had yielded a sufficient diagnostic sensitivity. Thus the recently introduced
      highly sensitive PCR methodology could be a solution and was thus studied. Assays
      for PCR amplification and subsequent identification of B. burgdorferi specific
      sequences were established and used. For all assays the analytical sensitivity
      was a few genome copies using purified DNA as template. The efficacy of PCR was
      initially evaluated using tissue samples from experimentally infected gerbils in
      order to start with biological samples a priori known to contain B. burgdorferi.
      B. burgdorferi DNA was detectable in 88% of the specimens. Thus the diagnostic
      sensitivity of PCR was comparable to and even higher than in vitro culture. PCR
      was significantly more sensitive than a histological B. burgdorferi specific
      immunophosphatase-staining method. The utility of the PCR was then tested for
      identification of B. burgdorferi DNA in skin biopsies from 31 patients with
      erythema migrans. The sensitivity of PCR was 71%, which was superior to culture
      and serology. Based on own and otherwise published results there is clear
      evidence for PCR being the most sensitive and specific test for detection of B.
      burgdorferi in skin biopsies from patients with both early and late
      dermatoborreliosis. However, since the clinical diagnosis of dermatoborreliosis
      in most instances is easy, an invasive procedure as a skin biopsy, will only be
      justified in patients with an atypical clinical presentation. The most frequent
      and serious manifestation of disseminated Lyme borreliosis is neuroborreliosis.
      PCR was applied to 190 patients with untreated and confirmed neuroborreliosis. B.
      burgdorferi DNA was detectable in 17-21% of CSF samples from patients with
      neuroborreliosis. In patients with very early neuroborreliosis (< 2 weeks), still
      being negative for specific intrathecal antibody synthesis, a positive PCR was
      more frequent than in patients with longer disease duration. PCR can be used as a
      diagnostic aid in these patients. However, in general the measurement of specific
      intrathecal antibody production in patients with neuroborreliosis was superior to
      PCR. In urine samples from patients with Lyme borreliosis the diagnostic
      sensitivity varied, generally showing a low reproducibility. Urine is thus not
      regarded as a suitable sample source for B. burgdorferi PCR. The reason may be
      the variable presence of Taq polymerase inhibitors. Based on a semi-quantitative
      detection system for amplicons, reflecting the input amount of specific DNA and
      thus the density of spirochetes in the clinical samples high amounts of DNA were
      found in skin biopsies whereas especially in urine the amount of DNA was low.
      When the present study was initiated there was no accepted classification of B.
      burgdorferi. A heterogeneity among B. burgdorferi strains might have important
      implications for understanding the epidemiology and different clinical
      presentations (dermatoborreliosis versus neuroborreliosis) and courses (self
      limiting versus chronic disease). Furthermore, strain differences were of
      importance for selection of suitable antigens for diagnostic assays and for
      vaccine development. Since then, B. burgdorferi isolates have been studied by
      phenotypic and genotypic traits and have been shown to be highly heterogeneous.
      Our first approach was to genotype a panel of human B. burgdorferi isolates by
      restriction fragment length polymorphism (RFLP) of three genes. Thereafter,
      sequencing and dideoxy fingerprinting of ospA was applied. By RFLP the strains
      could be differentiated into two to five groups. The RFLP classification was
      compared with four different phenotypic and genotypic methods including the rRNA
      typing. Results obtained with the different methods correlated highly and
      confirmed the meanwhile accepted taxonomic classification by Baranton et al.,
      According to this the term B. burgdorferi sensu lato comprises three different
      human pathogenic genospecies B. burgdorferi sensu stricto, B. garinii and B.
      afzelii. All three genospecies have been isolated among Danish patients with Lyme
      borreliosis and are thus prevalent in Denmark. Since isolation of B. burgdorferi
      from patients with Lyme borreliosis is laborious and often unsuccessful molecular
      typing methods based on PCR are recommended obviating the need for isolation by
      prior culture. Of special interest was to study a possible association of
      neuroborreliosis to certain B. burgdorferi genospecies, indicating species
      depended organotropism. By RFLP all six CSF isolates tested belonged to B.
      garinii and that 6 out of 7 isolates from patients with acrodermatitis chronica
      atrophicans belonged to B. afzelii. Due to the low culture yield of B.
      burgdorferi from CSF, the association of B. garinii and neuroborreliosis was
      further studied by sequence analysis and dideoxyfingerprinting analysis of ospA
      PCR amplicons obtained from CSF samples from patients with neuroborreliosis.
      Phylogenetic analysis showed that in 11 out of 13 patients B. garinii DNA was
      found in CSF. These data strongly supports the hypothesis that B. garinii is the
      principal agent of Lyme neuroborreliosis in Europe. Similarly it was shown that
      B. afzelii is associated with acrodermatitis chronica atrophicans and thus
      dermatoborreliosis. Due to a strain dependent different selection pressure in
      culture only PCR based methods can be used to answer whether mixed infection in
      patients specimens occur. Our data indicate that mixed infections in humans if
      ever are rare.

PMID- 11985119
TI  - Effectiveness of a dental gel to reduce plaque in beagle dogs.
AB  - Tooth brushing is considered a superior technique for reducing plaque
      accumulation. Chemical agents may be used to reduce plaque accumulation on tooth
      surfaces since many owners may not be willing or able to brush their dog's teeth.
      Following a professional teeth cleaning procedure, a dental gel containing
      chlorhexidine was applied in 11 dogs BID for 7-days, while 11 other dogs received
      a control dental gel applied in the same manner. Dogs in the treatment group had
      significantly less plaque accumulation during the trial period compared with dogs
      in the control group. The dental gel applied in the study reported here decreases
      plaque accumulation in the short-term and may be beneficial in reducing the
      severity of gingivitis and associated periodontal disease if provided on a long
      term basis.

PMID- 11985120
TI  - Effects of a dental food on plaque accumulation and gingival health in dogs.
AB  - Recent studies have demonstrated that typical dry dog foods have significantly
      less efficacy in reducing accumulation of dental substrates compared to a
      specifically formulated and processed dental food. This study compared the
      effects of a typical dry food and a dental food on plaque accumulation and
      gingival inflammation in dogs during a 6-month period. Daily feeding of the
      dental food significantly reduced plaque and gingivitis by 39% and 36%,
      respectively, compared with daily feeding of the typical dry food. Feeding a food
      that decreases plaque accumulation and reduces gingivitis contributes to canine
      oral health maintenance.

PMID- 11985121
TI  - Lingual calcinosis circumscripta in a dog.
AB  - Calcinosis circumscripta occurs rarely in dogs and cats, especially in the oral
      cavity. This case report describes the diagnosis and management of lingual
      calcinosis circumscripta in an eight-month-old, intact/male German shepherd-cross
      dog. An excellent prognosis for this disease may be achieved when the patient is
      managed as described in this report.

PMID- 11985122
TI  - Management of bilateral, pathologic, mandibular fractures in a dog.

PMID- 11985123
TI  - Gingival hemangiosacroma in a dog.

PMID- 11985124
TI  - Surgical extraction of the mandibular first molar tooth in the dog.

PMID- 11985125
TI  - Elevated lipase level always means pancreatitis?

PMID- 11985126
TI  - Keeping an eye on cardiovascular risk. A practical, case-study approach to
      assessment in office practice.
AB  - Primary care physicians typically encounter patients who are not at obvious risk
      for CAD but who nonetheless need and can benefit from lipid-lowering therapy.
      Applying algorithms or scoring systems can be helpful in estimating an individual
      patient's risk, but the basic tools available in everyday clinical practice can
      be used to alert physicians to elevated CAD risk in their patients. Those
      patients whose LDL-C level is at or above 220 mg/dL (5.69 mmol/L) should
      routinely and deservedly get clinical attention, but they account for only 2.5%
      to 5% of the population. Those with an "average" LDL-C level number in the
      millions, and from this patient pool come the coronary events that fill clinics
      and hospitals. Aggressive treatment approaches are required to meet NCEP
      objectives, and every indication suggests that these goals are just the minimum.
      The third report of the NCEP Expert Panel on Detection, Evaluation, and Treatment
      of High Blood Cholesterol in Adults (Adult Treatment Panel III) has broadened the
      indications for drug therapy, reclarifying diabetes and peripheral vascular or
      cardiovascular disease equivalents and using a global evaluation concept, which
      will identify 30 million Americans in need of drug treatment. The statins safely
      and effectively lower LDL-C levels, which is the basis for instituting drug
      therapy, according to NCEP guidelines. Using these drugs also raises HDL-C
      levels, which is somewhat protective, and decreases triglyceride levels. The
      efficacy of statin therapy in both primary and secondary prevention of CAD is now
      well established. If used more often when dietary therapy fails, which happens
      quite often, and in doses sufficient to work effectively, statins have the power
      to turn the corner on the prevention and treatment of atherosclerotic coronary
      disease in the United States.

PMID- 11985127
TI  - Black-dot tinea capitis. Patchy hair loss is common in pediatric patients.

PMID- 11985128
TI  - Tolerating the intolerable. How do physicians thrive in an increasingly regulated
      profession?

PMID- 11985129
TI  - Who should be screened for TB?

PMID- 11985130
TI  - Patient notes: chronic fatigue syndrome.

PMID- 11985131
TI  - Unresolved issues in diabetes screening.

PMID- 11985132
TI  - Tension-type, the forgotten headache. How to recognize this common but
      undertreated condition.
AB  - Tension-type headache is the most prevalent headache type, affecting most women
      and men at some time in their lives, and can impair job productivity and
      interfere with family and social time. However, despite its impact, tension-type
      headache is also the most misunderstood headache type. Because of these
      misperceptions, many affected people are reluctant to seek medical treatment. In
      this article, Dr Mueller discusses possible triggers of tension-type headache,
      appropriate evaluation, and management with pharmacologic, nonpharmacologic, and
      alternative therapies.

PMID- 11985133
TI  - Cardiovascular disease and the kidney. Tracking a killer in chronic kidney
      disease.
AB  - The interlinking of CVD with CKD is undeniable. CVD accounts for more than 50% of
      all morbidity and mortality in patients with kidney disease who have undergone
      renal replacement therapy, and CVD is also prevalent in patients with mild and
      moderately severe kidney disease. To help address the elevated risks of these
      patients, primary care physicians need to maintain vigilance in (1) identifying
      patients who have CKD and (2) implementing strategies for reducing the prevalence
      of CVD in this population. It is essential that patients be screened for
      relatively mild kidney disease by measurement of serum creatinine and urine
      microalbumin and by calculation of the glomerular filtration rate in mL/min/1.73
      m2 using equations based on serum creatinine. Rigorous assessment of conventional
      risk factors, including dyslipidemia, hypertension, and diabetes, is also
      necessary to prevent the poor outcomes currently observed in persons with CKD.
      Routine use of ACE inhibitors and aspirin is encouraged in all patients with CKD,
      and strict glycemic and blood pressure control is recommended for optimal
      outcomes. In addition, patients should be screened and treated for risk factors
      particularly associated with kidney disease and CVD morbidity and mortality,
      including anemia, hyperphosphatemia, and hyperparathyroidism. Finally, physicians
      should be careful to avoid therapeutic nihilism in patients with kidney disease;
      those at highest risk of CVD are likely to receive the greatest benefit from
      cardiovascular therapies.

PMID- 11985134
TI  - Return of the painful leg ulcers. Antiphospholipid-antibody syndrome.

PMID- 11985135
TI  - Inflammatory rheumatologic disorders in the elderly. Unusual presentations,
      altered outlooks.
AB  - Comorbidities, metabolic alterations, immunosenescence, and use of drugs may
      affect the manifestation, clinical course, immunopathogenesis, and prognosis of
      inflammatory rheumatologic disease in older persons. These factors need to be
      considered in evaluation and treatment in the geriatric population. In this
      article, Drs Belostocki and Paget discuss rheumatologic disorders that typically
      occur in advanced age, as well as those that characteristically occur in younger
      patients but may present de novo in the elderly.

PMID- 11985136
TI  - Endocrine origins of rheumatic disease. Diagnostic clues to interrelated
      syndromes.
AB  - Heightened awareness of endocrine abnormalities is important in evaluation of
      patients presenting with musculoskeletal symptoms. Endocrine disorders such as
      diabetes, hyperthyroidism, hypothyroidism, hyperparathyroidism,
      hypoparathyroidism, hyperadrenocorticism, and acromegaly cause a unique array of
      rheumatic manifestations. Such conditions include Dupuytren's contracture, carpal
      tunnel syndrome, chondrocalcinosis, pseudogout, scleredema, and osteoporosis.
      Characteristic changes on radiologic evaluation and serum enzyme testing are
      additional clues to these atypical presentations. Consideration of a possible
      endocrine cause early in the evaluation may improve management in patients with
      such an underlying disorder.

PMID- 11985137
TI  - Cancer-associated neuromusculoskeletal syndromes. Recognizing the rheumatic
      neoplastic connection.
AB  - Several cancer-associated neuromusculoskeletal syndromes initially described in
      isolated case reports were later defined more thoroughly in population-based and
      prospective studies. The pathophysiologic basis of various paraneoplastic
      neurologic degenerations also has been established by use of cellular and
      molecular methods. Tumors may release humoral factors that affect the function of
      distant tissues. Tumor antigens can be recognized by the immune system, leading
      to generation of antibodies or T cells that can target normal tissue. Such
      mechanisms have been described for tumor-associated myasthenia gravis and
      paraneoplastic cerebellar degeneration. Epidemiologic data support the
      association between rheumatic diseases (e.g., dermatomyositis, Sjogren's
      syndrome, systemic sclerosis, hypertrophic osteoarthropathy) and cancer. The
      pathogenesis of this association remains to be clarified.

PMID- 11985138
TI  - Paediatric nurses's pain management practice.

PMID- 11985139
TI  - Advanced nurse practitioners in a hospital setting: the reality.

PMID- 11985140
TI  - Information sources for specialist nurses.

PMID- 11985141
TI  - The first Diana Team in Wales: an update.

PMID- 11985142
TI  - Children's nursing education: towards a consensus.

PMID- 11985143
TI  - Health and safety for parents.

PMID- 11985144
TI  - The asthma files: evaluation of a multimedia package for children's asthma
      education.
AB  - Children's knowledge of asthma triggers and the impact on children's knowledge of
      using 'The Asthma Files', an interactive, educational computer program, were
      evaluated in this pilot study. Thirty-one children aged between seven and 14
      years and diagnosed with asthma were recruited to the study. Ten boys
      participated in evaluating the triggers section and a questionnaire was used to
      determine their feelings about the program and retention of information. Children
      enjoyed using the package and knowledge about asthma triggers increased
      significantly. 'The Asthma Files' shows promise as an additional tool to augment
      existing education.

PMID- 11985145
TI  - Manual handling and nursing children.
AB  - The aim of this article is to highlight some of the unique challenges relating to
      handling children, such as: their stage of physical and cognitive development,
      their position in relation to the carer's centre of gravity, their level of
      comprehension and their ability to communicate.

PMID- 11985146
TI  - A post-colonial analysis of healthcare discourses addressing aboriginal women.
AB  - Annette Browne and Vicki Smye use post-colonial theoretical perspectives to
      inform a critical analysis of healthcare discourses related to cervical cancer
      among Canadian aboriginal women. They also examine how decontextualised
      discourses addressing aboriginal women's risks for cervical cancer can perpetuate
      negative stereotypical images of aboriginal women while downplaying or ignoring
      the historical, social and economic context of women's health risks.

PMID- 11985147
TI  - 'Cultural safety' and the analysis of health policy affecting aboriginal people.
AB  - Vicki Smye and Annette Browne explore the exportability of the concept of
      'cultural safety' from the healthcare literature in New Zealand to inform an
      analysis of mental health policy discourse affecting aboriginal communities in
      British Columbia, Canada. The moral issues raised are, they suggest, ones that
      nurses in research, policy and practice must attend to when providing health care
      to marginalised, disenfranchised populations.

PMID- 11985148
TI  - Representing 'others': avoiding the reproduction of unequal social relations in
      research.
AB  - In this paper, the final one in a series of four articles on post-colonial
      research, Tam Truong Donnelly argues that some researchers have represented
      'Others' in ways that tend to reproduce unequal social relations. Researchers
      undertaking cross-cultural studies must recognise how meanings are constructed in
      and through systems of representation, the article concludes.

PMID- 11985149
TI  - Peers and partners: a stakeholder evaluation of preceptorship in mental health
      nursing.
AB  - This article, by Cris Allen, describes a study that examined the issues and
      concerns of stakeholders involved in preceptorship in pre- and post-registration
      mental health nursing. A responsive evaluation methodology was used to capture
      views on the preparation and support needs of preceptors.

PMID- 11985150
TI  - Toward a post-colonial feminist methodology in nursing research: exploring the
      convergence of post-colonial and black feminist scholarship.
AB  - In this paper, Joan M Anderson explores post-colonial feminist scholarship,
      generated through the convergence of black feminist and post-colonial
      scholarship, and examines its use as a theory and methodology for nursing
      scholarship.

PMID- 11985151
TI  - The new gatekeepers.

PMID- 11985152
TI  - Goodbye to PREP.

PMID- 11985153
TI  - Born again.

PMID- 11985154
TI  - Against the odds [interview by Charlotte Alderman].

PMID- 11985155
TI  - What's it all for?

PMID- 11985156
TI  - Growing nurses.

PMID- 11985157
TI  - Special pleading.

PMID- 11985158
TI  - Drug tolerance.

PMID- 11985159
TI  - Extensive first-aid kit. Are you carrying yours?

PMID- 11985161
TI  - The comfort zone. Research looks at improving quality of life for older people.

PMID- 11985160
TI  - Keep an open mind on MMR vaccination.

PMID- 11985162
TI  - Nurse education. Learning valuable lessons.

PMID- 11985163
TI  - Getting the job done.

PMID- 11985164
TI  - Cancer care. Education proves a vital link.

PMID- 11985165
TI  - Children's nursing. Looking after our future.

PMID- 11985166
TI  - Mental health. All about satisfaction.

PMID- 11985167
TI  - Communication. Information central.

PMID- 11985168
TI  - Intensive care. A difficult move to make.

PMID- 11985169
TI  - Teamwork. Inner tensions.

PMID- 11985170
TI  - Leaders or managers: the drive for effective leadership.
AB  - In the light of government initiatives to develop effective clinical leadership,
      the author asks whether a leader is the same thing as a manager. While management
      implies leadership, leaders are not necessarily managers.

PMID- 11985171
TI  - Mental health needs of children and young people.
AB  - Nurses should have an understanding of the mental health needs of children and
      young people. In this article, Mervyn Townley introduces a number of concepts
      that relate to these needs.

PMID- 11985172
TI  - Midwives' supervision may show the way on professional conduct.

PMID- 11985173
TI  - Wider range of misconduct sanctions.

PMID- 11985174
TI  - Council considers annual medical checks for nurses.

PMID- 11985175
TI  - The Tissue Viability Society.

PMID- 11985176
TI  - The causes and management of foot ulceration.
AB  - Managing foot ulceration is a challenge for all concerned. This article argues
      that the key to successful management of ulceration lies with the accurate
      identification of the underlying cause of the ulcer and consideration of the
      additional factors that are likely to impair healing. The common causes of foot
      ulceration are discussed, the means of evaluation and assessment are outlined and
      appropriate management strategies are identified. As with all care pathways,
      patient concordance is essential in reaching successful clinical outcomes and
      foot ulceration is no exception.

PMID- 11985177
TI  - Grading review 'ignores' some mental health staff.

PMID- 11985178
TI  - The project nurse and pressure-relieving equipment.
AB  - This article describes the work of a project management nurse in improving
      accessibility and appropriate use of pressure-relieving equipment in an
      integrated (acute and community) trust. It examines key issues for future service
      development in the management and appropriate use of pressure-relieving
      equipment. The importance of education in maintaining the accuracy and process of
      recording pressure damage at ward level is also highlighted. One recommendation
      is that employing a pressure equipment assistant might improve the control and
      management of pressure equipment availability.

PMID- 11985179
TI  - Dutch nurses fear murder charges for mercy killings.

PMID- 11985180
TI  - The impact of diabetes on wound management.
AB  - Kate Springett discusses the management of chronic diabetic wounds in the lower
      leg and foot. The aim of the article is to enhance the practitioner's
      understanding of the pathogenesis of these wounds and to aid clinical assessment
      and management while working within local wound management guidelines.

PMID- 11985181
TI  - New transfusion safety role could help cut errors.

PMID- 11985182
TI  - Nurses get wider remit under care trust scheme.

PMID- 11985183
TI  - Genetic screening for Alzheimer's disease: what factors predict intentions to
      take a test?
AB  - The authors investigated factors that predict intention to take a genetic test
      for Alzheimer's disease (AD). The 449 men and women were surveyed in two groups:
      (a) those told that a positive result meant a 90% chance of developing AD
      (increased certainty) and (b) those told that a positive result meant a 50%
      chance of developing AD (decreased certainty). Participants completed measures of
      the Theory of Planned Behavior (TPB), anticipated regret, risk perception,
      likelihood of taking a genetic test for cancer, and AD risk factors. Just over
      50% of the variance in intentions was related to TPB variables, likelihood of
      taking a genetic test for cancer, number of people the participants knew who had
      AD, experimental condition, and anticipated regret. The subjective norm was the
      strongest predictor of intention in the increased certainty group, whereas
      positive belief was the strongest predictor in the decreased certainty group.

PMID- 11985184
TI  - Facilitation of patient involvement in care: development and validation of a
      scale.
AB  - The authors describe the development and validation of the Facilitation of
      Patient Involvement Scale, a 9-item measure of the degree to which patients
      perceive that their physicians actively facilitate or encourage them to be
      involved in their own healthcare. They first assessed the unidimensionality of
      the measure, conducting factor analysis in a pilot study of 236 individuals.
      Subsequently, they assessed the scale's reliability and validity with additional
      samples of 333, 338, 44, and 84 participants. Reliability of the scale was very
      high, with average Cronbach's alpha levels of .91. To test the validity of the
      scale, they used correlational and multiple regression analyses. The findings
      indicated that patients' satisfaction with their medical encounters was
      associated with patients' perceptions of facilitation; that perceptions of
      facilitation were also moderately correlated with general adherence patterns and
      preferred communication styles; and that patient age, gender, and education level
      were not relevant to perceptions that healthcare professionals promote patients'
      involvement in their own care.

PMID- 11985185
TI  - Alexithymia and body weight in obese patients.
AB  - The authors evaluated severely obese patients to determine whether being far
      different in body shape from the accepted standard may cause obese people to
      develop alexithymic personality traits. They evaluated the food- and weight
      related attitudes in obesity surgery patients and in long-term follow-up of those
      who had previously had biliopancreatic diversion (BPD) for obesity. One quarter
      of the obese patients had alexithymic characteristics without any modification
      following stable weight loss, a rate of alexithymia similar to that observed in
      the nonclinical population. Furthermore, the frequency of alexithymia and the
      patients' scores on the Toronto Alexithymia Scale were similar in obese and post
      BPD individuals. The authors concluded that being obese by itself does not
      influence the presence of alexithymic personality traits. However, they suggest
      that the improvement in food-related and weight-related attitudes following
      stable weight loss may be different in alexithymic and in nonalexithymic obese
      patients.

PMID- 11985186
TI  - Effect of music on anxiety of women awaiting breast biopsy.
AB  - The authors investigated the effect of music on the state anxiety of a sample of
      20 patients awaiting breast biopsy at a suburban medical facility. The patients
      were assigned alternately to either the control or experimental group. The
      individuals in the experimental group were given a 20-minute music-based
      intervention in a preoperative holding area, whereas the patients in the control
      group received the customary preoperative care. Clinicians measured blood
      pressure, heart rate, and respiration in both groups of patients, and the
      participants completed the State portion of the self-administered State-Trait
      Anxiety Inventory (STAI). After the patients completed the 20 minutes of music or
      of preoperative care without music, clinicians again measured the participants'
      vital signs and the patients completed the STAI. The authors' findings indicated
      that the posttest state anxiety and respiratory rates of the patients in the
      experimental group were significantly lower than those of the patients in the
      control group.

PMID- 11985187
TI  - Intraprofessional controversies: reflections on the stainless steel crown
      situation.

PMID- 11985188
TI  - Fluoride varnishes and caries development in primary tooth enamel: an in vitro
      study.
AB  - This in vitro study evaluated the effect of fluoride varnishes on caries
      development in primary tooth enamel using polarized light microscopic techniques.
      A total of forty extracted or exfoliated primary teeth with intact, caries-free
      smooth surfaces underwent a fluoride-free prophylaxis and soft tissue were
      assigned to one of the following groups: 1) duraphat (5 percent sodium fluoride,
      vanish, Colgate, n=10); 2) Duraflor (5 percent sodium fluoride, Pharmascience, n
      = 10); 3 Cavity Shield (5 percent sodium fluoride varnish, Omni, n=10); and 4)
      Control (n=10). An acid-resistant coating was applied to the specimens leaving an
      exposed window of sound enamel (5mm x 1mm). The fluoride varnishes were applied
      to the primary teeth according to the manufacturer's recommendation. Following
      thermocycling (500 cycles, 5-50 degrees C) of the fluoride varnish-treated and
      control teeth, a fluoride-free pumice toothbrushing was performed to remove
      visible and macroscopically (dissecting microscope at 16x) detectable fluoride
      varnish. An acid resistant coating was reapplied where necessary, leaving the
      fluoride varnish treated sound enamel window exposed. Following in vitro caries
      formation (2.2mM Ca, 2.2mM PO4 50mM acetic acid, 0.5ppm fluoride, pH 3.90),
      longitudinal sections (5 per specimen) were obtained and evaluated by polarized
      light microscopy for mean lesion depth. Comparisons were made among treatment and
      control groups.

PMID- 11985189
TI  - Microleakage of two polyacid-modified resin composites under different
      conditioning methods in primary teeth.
AB  - This study evaluated the effect of different conditioning methods on micro
      leakage in primary teeth. Fifty-one cervical cavities were prepared on the twenty
      six extracted primary molars and divided randomly into five groups. In Group I
      and IV phosphoric acid, in group 11 non-rinse conditioner (NRC) was applied. In
      group III and V no pretreatment was used. Groups I-III were restored with Prime &
      Bond NT and Dyract AP and Group IV-V restored with Syntac SC and Compoglass F.
      The restored teeth were stored for 24 hours in distilled water at 37 degrees C,
      immersed in 0.5 percent basic fuchsin for 24 hours. Dye penetration was
      determined using a stereomicroscope. The results revealed that although enamel
      microleakage was not affected by the conditioning method used in both restorative
      materials, pretreating the cavity with phosphoric acid had a positive effect on
      reducing the dentin microleakage compared with conditioning by NRC.

PMID- 11985190
TI  - Dental emergencies in a university-based pediatric dentistry postgraduate
      outpatient clinic: a retrospective study.
AB  - The purpose of this retrospective study was to determine the prevalence and types
      of dental emergencies occurring in a university-based, pediatric dentistry
      postgraduate outpatient clinic. All patients presenting for emergency dental care
      during scheduled clinic hours over a three year were identified, and their charts
      were retrieved. Each record was reviewed for demographic information, chief
      complaint and clinical diagnosis. Only those charts with both chief complaints
      and clinical diagnoses recorded were included in this study. A total of 816
      patients received emergency care, representing 15.3 percent of all patient
      treated during the study period. The patient population had a slight female
      predilection (53 percent female, 47 percent male) and a mean age of 5.1 years
      (range 10 days to 15 years). Ethnicity (39 percent African-American, 36 percent
      Hispanic, 24 percent Caucasian <1 percent Asian-American) was similar to that for
      the clinic in general. Reimbursement for dental care was primarily via Medicaid
      (91 percent) with <10 percent covered by insurance or payment by responsible
      parents. For one quarter of the children, the emergency visit was their first
      dental visit. Reasons for seeking emergency included 1) pain or discomfort due to
      caries [30.1 percent] with 27 percent due to early childhood caries; 2) dental
      trauma [23 percent];3) eruption difficulties [18 percent] with 27 percent due to
      early childhood caries; 2) dental trauma [23 percent];3 eruption difficulties [18
      percent];4) soft tissue pathoses [16 percent]; 5) problems with orthodontic
      appliances or space maintainers [10 percent]; and 6) lost restorations [2
      percent]. Pain and bleeding were the most common reasons for seeking emergency
      dental care. Most causes for seeking outpatient emergency dental care are disease
      processes which may be avoided by infant oral health and preventive dentistry
      programs and early treatment intervention.

PMID- 11985191
TI  - Primary incisor triplication defect.
AB  - Conjoining abnormalities occur in less than 1 percent of the population.
      Triplication of primary teeth is even a rarer phenomenon with a prevalence of
      0.02 percent. This study describes the clinical features and the light
      microscopic appearance of a case of triplicated primary teeth. The teeth with the
      conjoined defect were examined by light microscopy to evaluate the exact level
      and appearance of the fusion area. The light microscopic examination revealed
      grooves and cracks consisting of enamel and dentine in the fusion area, fusion
      was irregular and both dentin and cementum were confluent. It is concluded that
      the clinician should identify children were conjoined anomalies and should be
      aware of the oncoming problems.

PMID- 11985192
TI  - Evaluation of non-invasive treatment applied to occlusal surfaces.
AB  - The purpose of this study was to evaluate the efficacy of non-invasive methods of
      treatment for active incipent occlusal caries. Anamnesis, professional
      prophylaxis, and visual inspection were used to classify 250 Brazilian pre-school
      children. First permanent decayed molars (n=98) from thirty-one subjects (6
      years+ 6 months) were selected and divided into three groups. Group 1: fissure
      sealants with resin-modified glass ionomer - Vitremer (n=29); Group 2: fluoride
      varnish -Duraphat (n=36) and control group: tooth brushing and 0.2 percent NaF
      weekly mouthwashes (n=33). Four clinical evaluations were carried out over three,
      six, nine, and twelve months. Caries activity and progression were observed
      through clinical and radiographic evaluation. The results were analyzed by
      Fisher=s Exact test. After twelve months, the results showed 100 percent of
      arrestment of caries activity for Group 1, 83.3 percent for group 2, and 72.7
      percent for control group. At the same time, the results showed 0 percent of
      caries progression for group 1, 5.5 percent for Group 2, and 6.1 percent for
      control group. Group 1 showed a better inactivation property than the other
      groups (p<0.05). There were no statistically significant differences in caries
      progression among these groups (p>0.05). It was concluded that this non-invasive
      methods were able to arrest the progression of occlusal caries, but fissure
      sealant showed better results in controlling caries activity.

PMID- 11985193
TI  - Complication associated with general anesthesia: report of case.

PMID- 11985194
TI  - Quantification of the lamina dura and dentin density in children.
AB  - This study used 150 periapical radiographs of primary mandibular molars along
      with an aluminum stepwedge consisting of 5 steps from 2 to 10mm which were
      exposed and developed under standard conditions. A Mustek (Taiwan, R.O.C.)
      flatbed scanner with transparency adapter was used to digitize the radiographs. A
      600 dpi, 10 bit gray level scanning transparency scanning mode were used. The
      thickness of the lamina dura was measured with the electronic ruler whereas
      density of dentin was calculated using the density function of a software program
      (Image Tool 2.0). Dentin density of the bifuraction area was calculated as 7.42
      +/- 37 mm=A1 in primary second molars and 11.02 +/- 1.37mm = A1 for permanent
      first molar teeth. Differences in the thickness of the lamina dura in primary
      posterior teeth ranged from 0.23 +/- 0.01mm to 0.42 +/- 0.01mm.

PMID- 11985195
TI  - Restorative materials used on primary teeth: a comparative study between two
      European universities: Nice and Amsterdam.
AB  - A descriptive retrospective survey was carried in two European dental schools
      (UNSA - Nice and ACTA - Amsterdam), in order to compare the restorative materials
      used in deciduous dentition. Examination of 460 patient files showed that age and
      sex distribution among children in both cities was comparable. The dft scores
      were also comparable but the number of decayed teeth was higher in Nice (4.61 +/-
      2.68) than in Amsterdam (2.86 +/- 2.30). In Nice, composite resins, compomers and
      glass ionomers were all used in deciduous anterior teeth whereas only compomers
      were used in Amsterdam. As far as deciduous molars were concerned, composite
      resins and amalgams were used on small and large cavities respectively in Nice
      whereas in Amsterdam, compomers were once again preferred.

PMID- 11985196
TI  - Palatal lymphangioma: a case report.
AB  - Lymphangioma is a rare, congenital benign tumor involving vascular malformation,
      with a great potential for recurrence. It appears during the early years of life
      and therefore is highly common among children. We report here a five-year-old
      patient with a simple lymphngioma. The mother of the child reported she had noted
      the lesion in the palate after an injury in the area with a pen. The recommended
      treatment was surgical excision since this was a small and well-delimited lesion.
      Periodic clinical controls for 18 months showed that mucosa presented normal
      characteristics, with no signs of recurrence.

PMID- 11985197
TI  - Macrodontia of a mandibular second premolar: a case report.
AB  - Localized macrodontia is very rare. The majority of cases have been reported in
      mandibular second premolars. This paper describes the dental management of a
      child who presented with macrodontia of a mandibular right second premolar.

PMID- 11985198
TI  - EEC syndrome (ectrodactyly-ectodermal dysplasia-clefting): a clinical case
      report.
AB  - The EEC syndrome (ectrodactyly-ectodermal dysplasia -clefting) is defined as a
      multiple congenital anomaly syndrome characterized by ectodermal dysplasia,
      distal limb anomaly, cleft lip/palate, and lacrimal duct anomalies. This case
      report reviews and presents clinical symptoms and treatment of the EEC syndrome.

PMID- 11985199
TI  - Black stain and dental caries in schoolchildren in Potenza, Italy.
AB  - This study examined the correlation between dark pigmented dental plaque (black
      stain) and caries. Black stain was observed in 67 of 1086 schoolchildren (from 6
      12 years old). The mean DMF-T was 0.49 = 1.05 for children with black stain and
      0.97 = 1.40 for children with black without black stain (p<0.05). The results
      suggest an association between black stain and a decreased caries experience at
      least in the permanent dentition. Further studies are necessary to examine the
      etiology and whether or not black stain can protect against caries.

PMID- 11985200
TI  - Low birthweight babies grow older, but there could be many problems.
AB  - An increasing number of low birthweight babies are surviving into their teen
      years and beyond, but with lifelong problems- including physical, intellectual
      and behavior difficulties. In the past, the indicators and measures used to
      evaluate health outcome have been selected from the perspective of the health
      care provider. There have been considerable skepticism as to the ability of
      parents to provide data about the development of their children. But
      practitioners often must rely upon the parent/guardian of children (particularly
      children with developmental and /or emotional disabilities) for significant
      input. This input is essential, but should be considered within the context of
      raising a child with special health care needs.

PMID- 11985201
TI  - Children with both mental retardation and mental illnesses live in our
      communities and need dental care.
AB  - Children with mental retardation may also suffer from the dual condition of
      mental health problems. As a result of deinstitutionalization and mainstreaming
      of many of these youngsters, an increasing number reside in our communities and
      are dependent upon local dentists for services. A review of the complicating
      realities of these comorbidities is presented.

PMID- 11985202
TI  - A quarter of a million dollars to raise a child born in 2000: and if the child is
      disabled....
AB  - Raising children in the year 2000 and beyond will be expensive. A review of
      actual costs by expense categories and a variety of family demographic
      characteristics provides practitioners with an appreciation of the competitive
      financial realities faced by many families. An added review of the costs of
      raising children with disabilities adds further dimension to the financial
      pressures placed on many families.

PMID- 11985203
TI  - Pockets of childhood poverty persisted despite a strong economy in the late
      1990s: impact in special cases.
AB  - Governmental and private agency reports provide varying views on childhood
      poverty levels during the final years of the 1990s. A review of these reports
      reveals that significant levels of childhood poverty continue, particularly in
      single parent households. The impact on children with special health care needs
      is considered.

PMID- 11985204
TI  - Identifying risk factors for predicting caries in school-aged children using
      dental health information collected at preschool age.
AB  - The study was done to identify toddlers who have an increased risk of developing
      dental decay at school age. Six variables-Cariostat score, mother's ethnicity,
      evidence of baby bottle tooth decay, mother;s dental health status, toddler's age
      at first tooth, and frequency of brushing - showed a significant association with
      decay status at school age with odds ratios ranging from 1.89 to 2.63. The
      Cariostat score and the frequency of brushing remained significant in a logistic
      regression. No interaction terms were significant. The Cariostat caries activity
      test would be a useful screening tool for identifying toddlers most likely to
      develop decay or could be used periodically as the deciduous molars erupt and
      become colonized with oral bacteria. The findings confirm that good oral hygiene
      practices can have an impact on future dental health, and caregivers should be
      encouraged to brush young children's teeth regularly.

PMID- 11985205
TI  - Influence of oral health attitude of mothers on the gingival health of their
      school age children.
AB  - We investigated the influence of mothers' oral health attitudes on their
      children's gingival health level, in 257 pairs of mothers and children from an
      elementary school in Hiroshima. The Oral Rating Index for Children (ORI-C) was
      used for the gingival health examination, and the Hiroshima University Dental
      Behavioral Inventory (HU-DBI) was used to assess the oral health attitude of each
      mother. Subjects in mother and child pairs were divided into a lower grade group
      (L-group) (grades 1-3), and upper grade group (U-group) (grades 4-6). Gingival
      health i L-group children was 3.42 times higher in those whose mothers noticed
      plaque, and 2.68 times higher in those who received dental check-ups. However,
      ORI-C scores were not correlated to HU-DBI scores in the U-group. We concluded
      that the gingival health of children could be significantly influenced by the
      oral health attitude of their mothers up to approximately ten years of age.

PMID- 11985206
TI  - Trends in special care training in pediatric dental residencies.
AB  - Pediatric dentist are often regarded by the dental community as the specialty
      group best prepared to treat patients with developmental disabilities. This may
      be because it is the only specialty that receives formal training in behavior
      management techniques. A questionnaire was mailed to the directors of all 55 ADA
      accredited pediatric dental residency programs in the U.S. The purpose of the
      survey was two-fold: the first aim was to quantify the training that pediatric
      dental residents receive in providing care to persons with developmental
      disabilities. A second area of investigation addressed the issue of pediatric
      dentist continuing yo treat persons with developmental disabilities into
      adulthood. The survey determined that pediatric dental residency programs provide
      considerable training in "Special Care" dentistry. While adults with
      developmental disabilities continue to be treated in 48 percent of responding
      programs, 55 percent of the program directors stated outright that it should not
      be the role of pediatric dentist to provide treatment to this population.

PMID- 11985207
TI  - Profile of pediatric dental literature: thirty-year time trends (1969-1998).
AB  - The objectives of this study were to determine the importance of the various
      areas of research interest in the pediatric dental literature and to measure
      their changes over a thirty-year period (1969-98). The Journal of Dentistry for
      Children and Pediatric Dentistry were reviewed by direct physical reference
      review and the publications categorized by research area. Frequency distribution
      and time series analyses were performed. There were 2.848 publications included
      in the study. Oral medicine, pathology and surgery remained the largest research
      area throughout the study period accounting for one-third of the publications.
      Time trends showed an increase in the following research areas: health services
      research; and pharmacologic behavior management; and an decrease in the following
      research areas: child behavior and nonpharmacologic behavior management; dental
      trauma; growth and development and orthodontics; and pulp therapy and
      medicaments. Time series analysis showed a strong negative correlation between
      the proportion of publications listed under pharmacologic behavior management,
      and child behavior and nonpharmacologic behavior management. In conclusion,
      pediatric dental literature reflected the trends in clinical practice.

PMID- 11985208
TI  - Establishing partnerships with social services agencies for community health
      education.
AB  - Nursing education is currently faced with many changes in both the academic and
      clinical environments. A significant challenge is to provide students with
      meaningful clinical placements. Experiences in clinical placements allow students
      to test assessment, critical thinking, communication, and decision-making skills
      in real and culturally diverse world situations. Nursing faculties need to
      develop new and innovative approaches for students to gain the necessary clinical
      experience. This article describes a community health clinical placement designed
      and implemented through a partnership of academic and social service
      organizations. It details the conception, growth, and development of student
      nursing clinics based in elderly and disabled housing sites.

PMID- 11985209
TI  - Examining health problems and intensity of need for care in family-focused
      community and public health nursing.
AB  - The purpose of this study was to advance evidence-based family-focused community
      and public health nursing (C/PHN) practice by examining 2 important indicators of
      health need, family health problem labels, and intensity of need for care, and
      their relationship to each other. The Omaha System (OS; Martin & Scheet, 1992)
      was the framework used to classify the most common family health problems.
      Intensity of need for care was determined using the Community Health Intensity
      Rating Scale (CHIRS; Hays, Sather, & Peters, 1998). Secondary analysis of C/PHN
      clinical data was done using a descriptive correlational design (n = 205). An
      investigator scored the CHIRS and assigned OS family problems based on clinical
      record data. The mean number of family health problems per person was 4.40 (+/-
      2.06). The mean CHIRS total score was 33.9 (+/- 6.34). The total number of OS
      problems was significantly correlated with CHIRS total scores (r = .586, p <
      .001). Family problem labels and intensity of need for care both provide
      essential information for health need determination in C/PHN practice.

PMID- 11985210
TI  - Surveillance as a nursing intervention: use in community nursing centers.
AB  - The purpose of this multisite retrospective descriptive study was to describe the
      nature of surveillance as a nursing intervention within 3 urban community nursing
      centers (CNCs). Secondary analysis of clinical data was conducted for clients
      seen in 1995. The CNCs used the Automated Community Health Information System
      (Lundeen & Friedbacher, 1994), a relational database. Nursing diagnoses and
      interventions were described according to the Omaha Classification System (Martin
      & Scheet, 1992b). The sample included 1,506 unduplicated clients who received
      care during 5,248 encounters and was characterized by more adults 20 years and
      older (56.1%), women (71.0%), and African Americans (77.2%). The age range of the
      clients was infancy to 95 years (M = 29.90 years). Surveillance was a significant
      nursing intervention making up 27.1% of all interventions (7,557 of 27,898), and
      68.5% of the clients received surveillance. There was a significant relation
      between the provision of surveillance and age range, chi 2 (5, N = 1,427) =
      211.96, p < or = .001, V = .385, and gender, chi 2 (1, N = 1,501) = 17.90, p < or
      = .001, phi = .109. Clients who were 40 years and older and who were women were
      more likely to receive surveillance. Surveillance was provided most often for the
      diagnoses of circulation and nutrition. Health promotion and disease prevention
      diagnoses were more likely to prompt surveillance. The provision of surveillance
      was linked to age and developmental risk factors.

PMID- 11985211
TI  - Application of Roy's adaptation model when caring for a group of women coping
      with menopause.
AB  - This article details the application of Roy's (Roy & Andrews, 1999) adaptation
      model when caring for a group of women experiencing changes associated with
      menopause. The Roy model guided the assessment of the members' levels of
      adaptation and facilitated the management of stimuli to promote their adaptation.
      Nursing interventions focused on issues surrounding menopause including
      disturbance in body image and social isolation.

PMID- 11985212
TI  - Nursing clinics in elder housing: providing access and improving health care
      outcomes.
AB  - This article describes one approach to helping elder individuals residing in
      subsidized senior housing achieve better health outcomes by providing health
      promotion and disease prevention services at on-site student nursing clinics.
      Clinics operate 2 days a week in the community room at the elderly housing sites
      and are staffed by senior baccalaureate nursing students who are in their
      community health clinical rotation. The student nursing clinic outcomes
      demonstrate improvement in residents' health through increased access to care,
      better identification and management of hypertension, more involvement for
      residents with diabetes in monitoring and management of their conditions, and
      better preparation for emergency medical situations.

PMID- 11985213
TI  - [Cervical spondylodiscitis].
AB  - Eighty patients were treated for spondylodiscitis with the cervical spine
      involved in nine cases. Conservative treatment was applied in seven cases with
      Minerva jacket and antibiotics, and surgical treatment was applied in severe,
      rapidly, progressive, complicated cases and in patients with involvement of
      nervous system (two cases). The good and satisfactory results in both group were
      similar. These results show that when the indications are properly established,
      both conservative and operative methods have satisfactory results.

PMID- 11985214
TI  - [Controlled liberation of active principles by means of new galenic
      formulations].
AB  - Drugs inside a conventional galenic form are distributed between specific
      biological targets and other anatomical tissues. With the aim to obtain a more
      rational and a better therapeutic, one of the most promising possibilities by
      using the concept of vectorization: association of an active principle to an
      appropriate vector with the object to increase its action efficiency and
      efficacy. By this means, they do not just increase the affinity of the drug to
      the target but also active principle gets protected from a potentially hostile
      environment (hydrolytic enzymes, acid pH, etc.). The success in the extension of
      the applications of the vectorizacion depends more and more of an appropriate
      design, for what the fundamental objective of this revision will be the one of
      presenting the general characteristics and some of the current applications in
      these new galenic forms.

PMID- 11985215
TI  - [AZOOR. After whiplash injury].
AB  - PURPOSE/METHOD: To present a case of a 30 years old woman that suffered a car
      accident one year ago, diagnosed of cervical sprain. One month after the
      accident, the patient saw a black stein in the outer side of the visual field on
      the left eye. RESULTS/CONCLUSIONS: Brain CAT, evocate visual potentials, color
      test and MRI were within of the normality. According with the ophthalmic
      examination, visual field test and OCT (optical coherence tomography), the
      diagnosis was acute zonal occult outer retinopathy (AZOOR).

PMID- 11985216
TI  - [Genes and responsibility].

PMID- 11985217
TI  - [How and when will Alzheimer's disease will be cured].

PMID- 11985218
TI  - [Quinupristin/dalfopristin].

PMID- 11985219
TI  - [The use of the impact index as a quality measure in research].
AB  - In this article some considerations are made upon the use of the impact factor as
      a measure for the quality in research. A historical view of the term "impact
      factor" is presented together with other aspects to keep in mind when the impact
      factor is used as a measure of citations. In addition, some criticisms are
      pointed out in the use of the impact factor as a tool to evaluate the quality of
      research, funding, employment and tenure.

PMID- 11985220
TI  - Changes in the 2001 Joint Commission home care survey process.
AB  - These are just a few of the forthcoming changes facing accredited home care and
      hospice organizations. The next "Accreditation Strategies" column will review the
      changes in the standards from the 2001-2002 Comprehensive Accreditation Manual
      for Home Care, discuss the new aggregation rules, and explain what the changes
      mean for accredited home care and hospice organizations.

PMID- 11985221
TI  - Quality end-of-life care: where does nutrition fit?

PMID- 11985222
TI  - 101 uses for OASIS?

PMID- 11985223
TI  - Guidelines for developing clinical paths in your agency.

PMID- 11985224
TI  - Narcophobia. Part 1: defining he problem..

PMID- 11985226
TI  - Improving the performance of continuous care hospice nurses.

PMID- 11985227
TI  - Occupational injuries--practice the policy.

PMID- 11985228
TI  - When home is where the risk is.

PMID- 11985229
TI  - Percutaneous injuries in home healthcare settings.

PMID- 11985230
TI  - Is your phlebotomy technique putting you at risk?

PMID- 11985231
TI  - Guide to needle prevention devices.

PMID- 11985232
TI  - The impact of the Needlestick Safety and Prevention Act on home care and hospice
      organizations.
AB  - Administrators, managers, and clinicians need to be up-to-date on all aspects of
      the new Needlestick Safety and Prevention Act recently passed into law. This
      article gives the background and foundation needed to implement policies,
      procedures, and actions that will assure compliance with the law and increased
      worker safety.

PMID- 11985233
TI  - What to do if you're exposed to a bloodborne pathogen.
AB  - What happens when the healthcare worker is the one needing care? Occupational
      exposure to a bloodborne pathogen is a known risk for healthcare workers but one
      that we are often ill prepared to handle. Each healthcare worker must know what
      the risks are and how to immediately access specialized care. This article will
      outline what you should expect and do if you are exposed.

PMID- 11985234
TI  - Latex allergies: management and clinical responsibilities.
AB  - Natural Rubber Latex (NRL) is found in over 40,000 products and presents many
      challenges to provide "reasonable accommodations" to keep employees safe in the
      work environment. In addition, patient care must also be modified in order to
      keep patients who are latex sensitive safe. This article presents the background
      of latex allergies and describes how to better manage both the employee and the
      patient with this allergy based on the most current information.

PMID- 11985235
TI  - Needlestick safety alliance unites clinicians and device makers.

PMID- 11985236
TI  - Helping ease transitions to the end of life. Interview by Audrey Kinsella.

PMID- 11985237
TI  - Standards of practice: a measure of competence.

PMID- 11985239
TI  - Doing more with less and less with more.
AB  - The "devil is in the details" of any policy response. What forms such changes may
      take, and what research informs them, are critical to the profession as a whole
      and to practitioners on a daily basis. Research partnerships between home care
      agencies and university professors may provide rigorous, systematic, and
      validated findings necessary for meaningful solutions (Plotkin & Roche, 2000).
      The evidence of a dialogue between nursing researchers, home healthcare
      practitioners, and policymakers anticipating impacts on practice of changing
      fiscal and information-gathering requirements is scant. Such issues are in need a
      priority discussion by agencies, and collaborative investigative efforts between
      all involved.

PMID- 11985240
TI  - Medical review under PPS.

PMID- 11985241
TI  - What's the difference.

PMID- 11985242
TI  - Narcophobia. Part 2: the Solution.

PMID- 11985243
TI  - Take the frustration out of patient education.

PMID- 11985244
TI  - Using OBQI to improve assessment and management of pain.

PMID- 11985245
TI  - Who sets the standard for hospice care?

PMID- 11985248
TI  - Earlier detection than mammogram possible?

PMID- 11985247
TI  - Are there financial benefits of adding to the home health aide's role?

PMID- 11985249
TI  - Medicare = inadequate care?

PMID- 11985250
TI  - Home visit 2002.

PMID- 11985251
TI  - The value of ECG monitoring in the home.

PMID- 11985252
TI  - A clinical pathway for congestive heart failure.
AB  - This study has shown improved outcomes with the use of a clinical pathway.
      However, under PPS additional ways for coordination among healthcare providers
      and patients need to be developed to ensure improved care beyond those focusing
      on the use of the pathway. One recommendation is the use of telehealth.

PMID- 11985253
TI  - Ethics in the absence of truth.
AB  - Nurses are passionate about patients' rights; especially the right of all
      patients to full disclosure, autonomy, and decision making. When these patient
      rights have been violated by an absence of truth, by deception, or by lies,
      nurses become unwilling actors in a part they find neither wise nor ethical. This
      discomfort can negatively impact patient care and contributes to job
      dissatisfaction. This article examines real-life situations where the principle
      of veracity has been abused. Suggestions for resolving ethical concerns can help
      readers to approach similar situations in a new light.

PMID- 11985254
TI  - Wound care products: how to choose.
AB  - Working in PPS means that agencies and clinicians must determine which wound care
      regimen will reach the intended patient goal in the most cost-effective way in
      terms of supply and visit cost. This article outlines the specific rationale
      clinicians can use when assessing wounds and choosing the dressing(s) that are
      appropriate to meet patient and agency goals. Using the performance-based model
      approach, clinicians learn how to choose dressings based on product price versus
      treatment costs.

PMID- 11985255
TI  - Home healthcare and client outcomes.
AB  - This study examined the outcome measures of readmission to the hospital and
      change in functional status/quality of life. Patients were admitted to the
      hospital most commonly by the 15th visit indicating complications arise soon
      after home care initiation. Implications for more specific data related to
      acuity, family support, and outcomes are suggested to develop and evaluate
      strategies for cost-effective care. The potential for preventing hospitalizations
      may be diminished due to the cost containment strategies currently used by
      agencies in response to PPS.

PMID- 11985256
TI  - Teaching the use of walkers and canes.
AB  - Home care and hospice nurses frequently encounter patients who use assistive
      devices to safely remain mobile in their homes. Incorrectly used, these devices
      may contribute to falls. This article provides a review on the use and teaching
      of these devices to patients and caregivers. A physical therapist, occupational
      therapist, or rehabilitation nurse should be consulted for any questions about
      applying the guidelines in this article to patients.

PMID- 11985257
TI  - Teaching an insulin-dependent blind patient about self-care.
AB  - Today's home care nurse faces many challenges in providing patient-centered care
      while working within the guidelines set forth by the payor. A patient with Type 1
      diabetes who was blind and lived alone was referred to our agency. A
      multidisciplinary approach for diabetes education along with tools for the
      visually impaired led our patient to independent diabetes management while
      keeping within the managed care guidelines.

PMID- 11985258
TI  - [Y chromosome variations and hyplogroups from 15 biallelic markers in six Chinese
      populations].
AB  - By using 15 biallelic markers, 342 male individuals from six populations in China
      were genotyped with ASPCR (allele specific PCR). The 15 biallelic markers
      included M1 (YAP), M15 (9 bp insertion), M89 (C-->T), M9 (C-->G), M119 (A-->C),
      M50 (T-->C), M110 (T-->C), M103 (C-->T), M95 (C-->T), M88 (A-->G), M111 (2-bp
      deletion), M45 (G-->A), M122 (T-->C), M7 (C-->G) and M134 (1 bp deletion). The
      distribution of variation frequencies of 15 biallelic markers in six populations
      showed that with the extremely high frequencies of M9G (96.20% & 96.43%) and Han
      nationality displayed higher diversity than the four minority populations. It's
      noteworthy that M95T (82.14%) in Sichuan Han and M45A (18.57%) in Hui gave
      prominace to the two populations. The six populations displayed 34 (Fujian Han),
      21 (Sichuan Han), 14 (Mongol), 26 (Hui), 10 (Xibo) and 8 (Hezhe) haplogroups
      respectively with 2, 1, 2, 1, 2 and 2 prominent haplogroups among them.
      Furthermore, the haplogroup analysis revealed that one predominant haplogroup was
      shared in the four minority populations and even two predominant haplogroups were
      shared in Mongol, Hezhe and Xibo. Unlike Han populations, the minority
      populations showed strikingly different haplogroups which were close to the
      ancestral pattern. However, the two Han populations exhibited divergence between
      them with the distinct frequencies of M89T and M95T. With the comparison of the
      number of people sharing the common haplogroups between any two of the four
      minority populations, relative genetic distance among them was deduced.

PMID- 11985259
TI  - [A short tandem repeat polymorphism in the inducible nitric oxide synthase gene
      in Chinese population].
AB  - Polymorphism of the (CCTTT)n repeat, a short tandem repeats (STR) located in
      promoter region of the inducible nitric oxide synthase (iNOS) gene, was analyzed
      in a total of 316 Chinese healthy subjects. Twelve alleles and forty-nine
      genotypes were identified. Three alleles that had not been reported previously,
      namely 17-repeats, 18-repeats and 19-repeats, were found in Chinese population.
      Mendelian inheritance of the allele in a family composed of three generations was
      determined. Some of the observed allele frequency of this STR locus in Chinese
      differed significantly from that of Caucasians in England.

PMID- 11985260
TI  - [Polymorphism analysis of 825C/T of the G-protein beta 3 subunit in high risk
      population of hypertension in the northeast China].
AB  - PCR-RFLP was used for genotyping of GNB3 C/T in 133 patients with EH and 257
      healthy control subjects in the high risk population and in 98 patients with EH
      and 110 healthy control subjects in general population. Some biochemical tests
      were performed also. The association between the polymorphism and blood pressure
      was analyzed by the case-control study. Not association between GNB3 825C/T
      polymorphism and blood pressure was found in both populations. CT and TT
      genotypes in women of the high risk population are associated with diastolic
      blood pressure, serum sodium and calcium. Although GNB3 is not a susceptible gene
      of hypertension in the northeast Chinese, it still has some effects on regulation
      of the blood pressure in susceptible women.

PMID- 11985261
TI  - [Cloning and analysis of human alpha-1B glycoprotein precursor gene: a novel
      member of human immunoglobulin superfamily].
AB  - A cDNA of 1694 bp was cloned from human liver Marathon cDNA by means of Rapid
      Amplification of cDNA Ends (RACE). The cDNA has an open reading frame at 43-1530
      bp encoding 495 amino acid residues and a 17-residue signal peptide. There are
      four Igc2 domains in the translated polypeptide, which is highly homologous to
      the human alpha-1B glycoprotein isolated from human plasma. Upon this, we
      conclude that this cDNA is the alpha-1B glycoprotein precursor gene which has
      never been cloned before, and it may be a novel member of immunoglobulin
      superfamily and may involved in the cell recognition and the regulation of cell
      behavior.

PMID- 11985262
TI  - [Establishment of permanent lymphoblastoid cell lines of 47 patients with
      abnormal chromosome karyotype].
AB  - To increase the efficiency of in vitro transformation of human lymphocytes by
      Epstein-Barr virus (EBV) and establish permanent lymphoblastoid cell lines from
      patients with abnormal chromosome karyotype, B lymphoid cells were prepared from
      cryopreserved heparinized blood samples. The lymphoid cell pellet was resuspended
      with 0.5 ml medium of RPMI with 20% fetal calf serum(FCS), and added 2 ml virus
      containing superatant of the EB virus-producing cell lines by filtrated, and
      mixed. Four 25 cm2 cell culture bottles were put upright. A total of 2.5 ml of
      RPMI with 20% FCS was put in each of them. The blood-virus mixture was
      distributed among the four cell culture bottles as follows: Bottle I, Bottle II,
      Bottle III and Bottle IV were added with 0.3 ml, 0.6 ml, 1.2 ml and the rest
      respectively. The cells culture bottles were put into the cell culture incubator
      in an upright position. After 3 days the cells were puting new medium with 20%
      FCS as follows: Bottle I 3 ml, Bottle II 4 ml, Bottle III 5 ml and Bottle IV 6
      ml. After one week, the medium was changed again as described above. The medium
      change was conducted until the cells grew very fast. The right ratio between
      blood cells and virus titer can not be exactly determined for every blood sample,
      and therefore a dilution series with four different blood/virus ratios was set
      up. Due to the dilution series, addition of immune inhibitors like cyclosporine,
      was not necessary. Forty-seven permanent lymphoblastoid cell lines of patients
      with abnormal chromosome karyotype. Transformed cells were found in only one or
      two of the four cell culture bottles. The total successive rate increased up to
      97.87%. Of the four cell culture bottles, Bottle I, Bottle II, Bottle III and
      Bottle IV, the successive rates were 6.39%, 61.70%, 31.91% and 8.51%
      respectively. This method can be used for preserving large number of
      lymphoblastoid cell lines, and also provide enough research materials for further
      studies.

PMID- 11985263
TI  - [Pedigree analysis of captive giant panda].
AB  - Pedigree analysis of captive giant panda was conducted by Sparks Ver1.4 Software.
      The result shows that genetic drift has a strong effect on the loss of genetic
      diversity. And the dispersal of captive giant panda is an acute dangerous factor
      when all of these small populations would be declined if inbreeding happened. For
      this reason, all these small populations should be managed as a whole unit to
      approach the goal for long-term conservation.

PMID- 11985264
TI  - [The studies of the phylogeny of acridoidea based on mtDNA sequences].
AB  - The mtDNA Cyt b sequences (432 bp) were analyzed in 10 individuals from 8
      different families of Acridoidea in China. The homologous sequences were
      compared, the used frequency of nucleotide was calculated and the molecular
      phylogenetic tree constructed by Neighbor-Joining method using T. japonica as
      outgroup. The confidence of nodes in the trees was evaluated by bootstrap (1000
      replicates). These sequences were the middle part of Cyt b gene, and in the
      obtained sequences, A% + T% was about 70.4% and G% + C% only 29.6%. The sequence
      data revealed considerable variation in 177 nucleotide sites (about 41.0%) among
      the analyzed individuals from 8 different families. From every amino acid codon,
      A% + T% in the third site was higher (86.6%) than the other two sites and lower
      than other insects in the corresponding region. The NJ tree suggested that 11
      individuals from the 8 families clustered in 4 groups, among which Gomphoceridae
      and Pamphagidae firstly clustered and then together with Arcypteridae and
      Acrididae to form group I; Cluster II was made of three species from
      Catantopidae, O. japonica, O. chinensis and O. intricata; Pyrgmorphidae and
      Oedipodidae formed group III and Chrotogonidae single as cluster IV,
      respectively. The phylogenetic relationships of the 8 families was: Chrotogonidae
      ->Pyrgomorphidae and Oedipodidae-->Catantopidae-->Acrididae-->Arcypteridae-
      >Gomphoceridae and Pamphagidae, which is little different from the morphological
      results.

PMID- 11985265
TI  - [Studies of relationship between the melanocortin-3 receptor gene and body weight
      in chicken for high and low weight lines' intercross].
AB  - Genetic studies in mice have demonstrated a complementary role for the
      melanocortin-3 receptor (MC3R) and MC4R in the control of energy balance.
      Knockout of the MC3R in mice revealed an exclusively metabolic syndrome and
      increased fat mass. In the present study, we found a total of 5 novel single
      nucleotide polymorphisms (SNPs) of the MC3R gene in the chickens of high weight
      (HW) and low weight (LW) lines from divergently selected for high or low body
      weight at 8 weeks of age in White Plymouth Rock. Only one of the 5 SNPs led to
      amino acid substitution (Leu-->Arg) in HW and LW lines animals: a T/G
      substitution at nucleotide (nt) position 452 of coding sequence. Three of the 5
      SNPs distinguished the birds from HW and LW lines: an A/G substitution at nt
      position 549 in LW line, an A/G substitution at nt position 882 in HW line, and a
      C/T substitution at nt position 894 in LW line, respectively. Another SNP was
      presented only in one of two HW line animals: a C/T substitution at nt position
      564. Of the 5 SNPs, only A/G polymorphism at nt position 549 is located within a
      Dde I restriction enzyme recognition site. We designed a PCR-RFLP test based on
      the enzyme Dde I and screened the chickens for HW and LW lines' intercross.
      Analysis of variance revealed a significant influence of the MC3R genotype on
      body weight in the chickens for both sex and abdominal fat mass in male chickens.
      The result suggests that the MC3R as a candidate gene can explain significant
      difference for body weight in the intercross chickens.

PMID- 11985266
TI  - [Polymorphism of porcine myostatin gene].
AB  - Myostatin(MSTN) gene is expressed specifically in developing and mature skeletal
      muscle, and the expression products of MSTN gene inhibits muscle growth and
      differentiation. The polymorphism of the porcine MSTN gene was researched by PCR
      SSCP. The SSCP was found in the MSTN gene exon 2 and exon 3. It showed three
      genotypes (CC, CT, TT) in exon 2 and two genotypes (AG, GG) in exon 3 in Large
      White pigs. The relationship between polymorphism in exons 2 and 3 and productive
      performance was analysed. Variance analysis showed that there was no significant
      relationship between the polymorphism in exon 2 and productive performance. But t
      test showed that there was a significant relationship between the polymorphism in
      exon 3 and back fat thickness (P < 0.05), there was also a relationship between
      the polymorphism in exon 3 and lean meat percentage, but not significant (P >
      0.05). The fragments with SSCP polymorphism in exon 2 and 3 were sequenced, the
      sequencing results showed that there were two single nucleotides mutation, i.e. A
      ->G at 1008 (exon 3) and G-->T at 480 (exon 2). Two mutations did not change the
      amino acid but brought an Apa I site in exon 3, and PCR-RFLP molecular marker
      technique was established with Apa I.

PMID- 11985267
TI  - [Detection and analysis of QTL for resistance to the brown planthopper,
      Nilaparvata lugens (Stal), in rice (Oryza sativa L.), using backcross inbred
      lines].
AB  - A mapping population of 98 BC1F9 lines (backcross inbred lines: BILs), derived
      from a backcross of Nipponbare (japonica)/Kasalath (indica)//Nipponbare by the
      single-seed descent methods, was used to detect quantitative trait loci (QTL) for
      resistance to brown planthopper (BPH), Nilaparvata lugens (Stal). Seedbox
      Screening Technique (SST) was applied to evaluate the reactions of two parents
      and 98 BILs to BPH at the seedling stage, and the entries were graded on ratio of
      dead seedlings. A total of three QTL controlling BPH resistance were detected on
      chromosomes 2, 10 and 12, respectively. Individual QTL accounted for between
      10.4% and 16.6% of the phenotypic variance, and the resistance of all the three
      QTL came from Kasalath, the moderate resistance parent. These QTL should be
      useful in breeding of varieties resistant to BPH in marker-assisted selection
      (MAS) program.

PMID- 11985268
TI  - [Identification of quantitative trait loci controlling F2 sterility and heading
      date in rice].
AB  - Ninety-six F2 lines derived from a cross between a japonica cultivar Taichung 65
      and an indica cultivar Bhadua were developed. At the first step, an RFLP linkage
      map based on the F2 lines was constructed. The RFLP map contained 94 RFLP makers.
      F2 sterility and heading date are important agronomic traits of rice; meanwhile
      heading date is related to many characters of agronomic importance including
      sterility. Quantitative trait locus (QTL) analysis was carried out to identify
      genes controlling F2 sterility and heading date. Both single factor analysis and
      interval analysis were applied for QTL analysis. Two QTLs for F2 spikelet
      sterility were newly detected on Chromosome 1 and 8. Five QTLs for heading date
      were detected on Chromosome 1, 4, 6, 8 and 10. Two of them on chromosome 1 and 10
      were newly detected. Near-isogenic lines are now under construction for further
      QTL analysis and gene mapping of these QTLs newly identified in this paper.

PMID- 11985269
TI  - [Molecular markers and its clone for salt tolerance gene in wheat].
AB  - Genetic and RAPD analysis were studied among [4] individuals in F2 segregated
      population originating from a cross between wheat cultivator Nongda 85021 (female
      parent, salt sensitive) and Chadian Red (male parent, salt tolerant). For genetic
      analysis and chi-square test gave a good fit of 1:2:1 ratio showing that one
      major gene was controlling the salt tolerant character in Chadian Red. DNA of F2
      population was extracted to develop tolerant and sensitive gene pools,
      respectively, based the BSA (Bulked Segregate Analysis). By RAPD (Randomly
      Amplified Polymorphic DNAs), 520 random primers were used to amplify the two
      types of gene pools. Only primer OPZ09 was found to be polymorphic with a
      fragment of 590 bp in the two parents, F1 and F2 populations. So, the specific
      fragment OPZ09-590 was, a RAPD marker linked to salt tolerance gene in Chadian
      Red. By the software JOINMAP (Version 1.4), the recombination was 5.674% and the
      linking distance was 6.557 cM. OPZ09-590 was extracted from the agarose and mixed
      with pUCm-T vector, then the vector was transferred into JM109. The clone was
      determined 591 bp after being sequenced. It indicated that the RAPD marker of
      salt tolerance gene in Chadian Red was OPZ09-591.

PMID- 11985270
TI  - [Development of Triticum aestivum-Leymus racemosus translocation lines NAU601 and
      NAU618 and their test-cross analysis with double ditelosomic].
AB  - Two Triticum aestivum-Leymus racemosus disomic translocation lines were selected
      and identified from irradiated progenies of T. aestivum-L. racemosus addition
      lines Lr. 2 and Lr. 7 by somotic chromosome C-banding and fluorescence in situ
      hybridization by using L. racemosus genomic DNA as probe. NAU618 (MS142-3), 2n =
      44, is a disomic addition translocation line with a pair of translocated
      chromosome consisting of 5/6 length of L. racemosus chromosome Lr. 7 (including
      centromere) and 1/3 distal part of wheat chromosome 1A short arm. The alien
      segment is about 4/5 of the length of translocated chromosome. NAU601 (MS101-4),
      2n = 42, is a disomic translocation lines with a pair of translocated chromosome
      consisting of 4B short arm, interstitial 1/3 part of 4BL and almost Lr. 2S, the
      alien segment is a half of the long arm of translocated chromosome. The results
      of test-cross analysis with T. aestivum c. v Chinese Spring double ditelosomic
      combine meiotic chromosomes C-banding indicated that the translocated chromosomes
      in these two translocation lines were involved in chromosome 1A and 4B
      respectively. Their resistance to wheat scab was identified using single floret
      inoculation in three successive years and showed that the resistance of
      NAU618(MS142-3) was similar to that of resistant check variety Sumai 3, and
      NAU601(MS101-4) was lower than Sumai 3 but much higher than susceptible parent
      Chinese Spring.

PMID- 11985271
TI  - [Structural changes of 4V chromosome of Haynaldia villosa induced by gametocidal
      chromosome 3C of Aegilops triuncialis].
AB  - Chromosome 3C of Aegilops triuncialis was discovered with ability to be
      transferred preferentially in the case of its monosomic status in wheat
      background, whereas, those gametes without 3C would result in chromosome
      structural changes including deletions and translocations. In the present study,
      Triticum aestivum-Haynaldia villosa substitution line 4V(4D) developed in our
      laboratory, was crossed to T. aestivum c.v. Norin 26-Aegilops triuncialis 3C
      addition line, and the hybrids F1 were then backcrossed with common wheat in
      order to induce structural changes of 4V. Both chromosome C-banding and genomic
      in situ hybridization was applied to search such chromosome variations. In this
      case, total genomic DNA of Haynaldia villosa was labelled by Biotin-11-dUTP as
      probes and total genomic DNA of Chinese Spring as the block. Moreover, several
      chromosome changes within common wheat such as isochromosome 1BL.1BL(B39-2) and
      others were also revealed. The result indicated that two translocation lines
      T4VL.3AS(A47-10-3) and T4VS.4DL(A47-25-4), two telocentric chromosome lines A47-7
      2(4VS) and A47-32-2(4VL), and two isochromosomes including 4VS.4VS(A47-23) and
      4VL.4VL(A412-5-4) were identified from BC1F2 or BC1F3. This result indicated that
      gametocidal chromosome 3C of Aegilop triuncialis could effectively induce
      structural changes of both chromosome 4V of Haynaldia villosa and chromosomes of
      wheat.

PMID- 11985272
TI  - [The cDNA-AFLP differential display in developing anthers between cotton male
      sterile and fertile line of "Dong A"].
AB  - cDNA-AFLP, an effective method for mRNA differential display, was employed to
      compare the gene expression in developing anthers between the male sterile and
      fertile plants of cotton (Gossypium hirsutum L.) cultivar, Dong A. In the micro
      spore stage, there were more differential bands of cDNA-AFLP than that in the
      meio-phase stage. Among 64 differential fragments produced by cDNA-AFLP, three
      were randomly selected for further analysis. RNA dot blotting showed that the
      GHA27 transcript was expressed mainly in floral tissues; on the other hand, the
      GHA28 and GHA47 transcripts were present specifically in anther. BLAST analysis
      demonstrated that GHA27 was highly similar to the plant ADP-ribosylation factor
      genes, while GHA28 and GHA27 were shown no significant similar to any sequences
      in the available databases.

PMID- 11985273
TI  - [Inheritance of organelle genomes of the somatic hybrid between Cleopatra
      mandarin (Citrus reticulata) and flying dragon (Poncirus trifoliata)].
AB  - Cleaved Amplified Polymorphic Sequence (CAPS) was successfully applied to analyze
      the organelle composition of three eight-year-old trees of the somatic hybrid
      between Cleopatra mandarin (Citrus reticulata) and Flying Dragon (Poncirus
      trifoliata). Five chloroplast and five mitochondrial universal primer pairs were
      used. All chloroplast primer pairs (rbcL-rbcL, rbcL-PSA I, TrnH-Trnk, TrnD-TrnT,
      TrnK-TrnK) and three (nad 1 exon B-nad 1 exon C, 18S rRNA-5S rRNA, nad 4 exon 1
      nad 4 exon 2) of the five mitochondrial primer pairs, were efficiently amplified,
      but no polymorphism was detected, when the PCR products were digested by eleven
      restriction endonucleases, including, Hin6 I, Bus RI, Taq I, Msp I, HinfI, AluI,
      Dra I, EcoR I, Hind III, BamH I and Pst I respectively, three polymorphic cpDNA
      CAPS markers (rbcL-rbcL/Hin 6 I, TrnD-TrnT/BusR I, TrnD-TrnT/Taq I) and one mtDNA
      CAPS marker (nad 1-nad1/Msp I) were found. The results showed that cpDNA in the
      somatic hybrid plants came from Flying Dragon, the mesophyll parent, and mtDNA
      from Cleopatra mandarin, the embryogenic suspension parent uniformly. In order to
      prove the reliability of CAPS results, and to get more detailed information about
      the mtDNA inheritance, RFLP analyses was conducted. Genomic DNA of the somatic
      hybrids and their corresponding parents were digested by five restriction
      endonucleases (Dra I, EcoR I, Hind III, BamH I and Pst I), and hybridized with
      five mitochondrial probes (Cob, Pro 2, Pro I, atp 6, 26S rRNA) as well as one
      chloroplast probe, i.e. the PCR product of Flying Dragon with the primer pair of
      trnd 1-trnt 1. The results were in line with those of CAPS, and no novel bands
      were detected, which indicated that no organelle DNA recombination or
      rearrangement have been detected in the hybrid plants. The research showed that
      novel pattern of nuclear-mitochondria-chloroplast interaction could be reached
      via protoplast fusion.

PMID- 11985275
TI  - The dis-ease of nursing academia: putting the vulnerability 'out there' (Part 2).
AB  - In this article, the second in a two-part series on research investigating the
      lived experiences of women nurse academics in australia, the results of the study
      are revealed. The major findings indicated that the Australian university system
      remains competitive and non-supportive of women nurse academics. The women who
      participated in this study had a strong desire to share their stories and reveal
      their vulnerability associated with their everyday life experiences in
      universities. Cultural descriptions revealed the complexity of women nurse
      academics' vulnerability as well as the dimensions of emotional resilience and
      optimism for their associated emotional healing.

PMID- 11985274
TI  - Simultaneous expression of CS3 colonization factor antigen and LT-B/ST fusion
      enterotoxin antigen of enterotoxigenic Escherichia coli by attenuated Salmonella
      typhimurium.
AB  - LT and ST are the main enterotoxins of enterotoxigenic Escherichia coli (ETEC)
      found in clinical isolates, and CS3 (the common antigen in the CFA/II family of
      fimbrial antigens) is one of the most prevalent antigens of colonization factors.
      The genetic determinants encoding CS3 and LT-B/ST fusion toxin were manipulated
      so that these important antigens are expressed simultaneously in attenuated
      Salmonella typhimurium oral vaccine strain X4072. These antigens produced by
      X4072 (pXZL88) could be recognized with monospecific CS3, LT or ST antibodies
      respectively. The specific antibodies against CS3, LT and ST could be detected.
      In the sera of immunized mice via oral route with the live bacteria.
      Significantly, the antibody to ST was able to neutralize the biological activity
      of native ST. This prototype construct may be proved to be useful in
      investigating the live vector approach to immunoprophylaxis of ETEC diarrhea
      disease.

PMID- 11985276
TI  - Welcome to the training bazaar.

PMID- 11985277
TI  - Staying power.

PMID- 11985278
TI  - Casualties of the property boom.

PMID- 11985279
TI  - A steep learning curve.

PMID- 11985280
TI  - Same old story, different ending.

PMID- 11985281
TI  - Quitters' tips.

PMID- 11985283
TI  - 'I was regarded as one of the girls'.

PMID- 11985282
TI  - Medical values for money.

PMID- 11985285
TI  - The cost of death deferred.

PMID- 11985284
TI  - Time for beds.

PMID- 11985286
TI  - RP-forme fruste.

PMID- 11985287
TI  - The effect of fluoxetine on the pharmacokinetics and safety of risperidone in
      psychotic patients.
AB  - In this open, 30-day trial, the pharmacokinetics, safety and tolerability of a
      combination therapy of risperidone (4 or 6 mg/day)and fluoxetine (20mg/day from
      day 6) were evaluated in 11 psychotic inpatients. CYP2D6 genotyping revealed that
      3 and 8 patients were poor metabolizers (PMs) and extensive metabolizers (EMs) of
      debrisoquine, respectively. The mean (+/- SD) AUC of risperidone increased from
      83.1 +/- 46.8 ng.h/ml and 398.3 +/- 33.2 ng.h/ml (monotherapy) to 345.1 +/- 158.0
      ng.h/ml (p < 0.05) and 514.0 +/- 144.2 ng.h/ml (p < 0.001) when coadministered
      with fluoxetine in EMs and PMs, respectively. The AUC of the active moiety
      (risperidone plus 9-hydroxy-risperidone) increased from 470.0 +/- 170.0 ng.h/ml
      to 663.0 +/- 243.3 ng.h/ml (p < 0.05)and from 576.3 +/- 19.6 ng.h/ml to 788.0 +/-
      89.1 ng.h/ml (ns) in EMs and PMs, respectively. In EMs, the AUC of 9-hydroxy
      risperidone remained similar (monotherapy vs. combination therapy: 386.8 +/-
      153.0 ng.h/ml vs. 317.7 +/- 125.2 ng.h/ml, ns),whereas it increased in PMs (178.3
      +/- 23.5 ng.h/ml vs. 274.0 +/- 55.1 ng.h/ml (p < 0.05)). Ten of the 11 patients
      showed a clinical improvement (reduction of 20% or more in total PANSS score and
      70% on the mean MADRS score compared to baseline). The severity and incidence of
      extrapyramidal symptoms and adverse events did not significantly increase when
      fluoxetine was added.

PMID- 11985288
TI  - Felix T. Rapaport, M.D. Founding editor, Transplantation proceedings.

PMID- 11985289
TI  - Nursing home administrator compensation: pay equity and determinants of salary.
AB  - This study evaluates the issue of gender-based pay inequality. Male NHAs earn 7
      percent more than female NHAs, but factors such as education, experience, tenure,
      facility size, ownership, location, competition, and emphasis on private pay
      census account for the difference. The findings, however, indicate that racial
      inequalities and gender differences among married NHAs may be present, requiring
      further investigation. Key implications of the results are discussed.

PMID- 11985290
TI  - A post-1990s assessment of strategic hospital alliances and their marketplace
      orientations: time to refocus.
AB  - In past years, many SHAs formed in local urban markets to better compete for
      managed care contracts. In response to 1990s forces, these SHAs appear to have
      adapted product, production, and selling orientations to their markets, aimed at
      large institutional purchasers of health care. However, health care markets have
      evolved differently than anticipated. SHAs and their hospitals should now adopt
      the marketing orientation and focus more on patients and enrollees.

PMID- 11985291
TI  - Business ethics and health care: a stakeholder perspective.
AB  - This article examines the recent controversy in health care delivery about
      whether it should be conceptualized as a business. The current debate implicitly
      appeals to a common understanding of business and business practices that is no
      longer very useful. This common notion, which the authors call "cowboy
      capitalism," conceptualizes business as a competitive jungle resting on self
      interest and an urge for competition in order to survive. The authors suggest
      that stakeholder capitalism offers a more useful framework for the dialogue about
      health care reform.

PMID- 11985292
TI  - Evaluating stakeholder management performance using a stakeholder report card:
      the next step in theory and practice.
AB  - In the highly competitive health care environment, the survival of an
      organization may depend on how well powerful stakeholders are managed. Yet, the
      existing strategic stakeholder management process does not include evaluation of
      stakeholder management performance. To address this critical gap, this paper
      proposes a systematic method for evaluation using a stakeholder report card. An
      example of a physician report card based on this methodology is presented.

PMID- 11985293
TI  - Professional association membership by nursing facility administrators and
      quality of care.
AB  - This article compares 4,220 nursing homes whose administrators belonged to a long
      term-care professional association to 12,322 nursing homes whose administrators
      did not belong to a long-term-care professional association. The research results
      show that professional membership is associated with higher quality of care on
      several measures and with a higher private-pay proportion. The study suggests
      that these facilities do not do better because they have more resources or
      because they care for less-challenging residents-they do better because they have
      a professional association as a resource.

PMID- 11985294
TI  - Valued stakeholders or unwanted stepchildren?--A stepfamily theory regarding
      physician group divestitures.
AB  - Drawing upon stakeholder and stepfamily literature, this article identifies
      critical factors that determine physician group acquisition retention or
      divestiture. Based on the stepfamily literature propositions are developed
      regarding why many physician group acquisitions do not work.

PMID- 11985295
TI  - Rethinking the probative value of evidence: base rates, intuitive profiling, and
      the "postdiction" of behavior.
AB  - It is argued that American courts may be routinely admitting evidence with little
      to no probative value and great potential for prejudicial impact. This may be
      particularly likely with regard to what is essentially "intuitive profiling" or
      "stereotype" related evidence, defined herein as evidence suggesting that the
      defendant (or other party), or his (her) behavior, fits intuitive "profiles" (or
      stereotypes) of the type of person likely to commit the crime or behavior in
      question. In other words, "intuitive profiling" evidence is admitted to
      "postdict" behavior Formal empirically based "profiling" evidence (testimony
      regarding the fit of a defendants characteristics or behaviors to formal or
      scientific profiles of the typical perpetrator of the crime in question) for use
      to prove guilt is inadmissible in American courts. However, we suggest that
      everyday use of informal intuitive profiles underlies both judicial
      determinations of probative value (diagnosticity), and thus admissibility, of
      evidence, and jurors' use of the evidence in determining guilt. Demonstrations of
      the use of base rate information to evaluate the probative value of such
      intuitive profiling evidence both as evidence of guilt and as evidence of
      innocence are provided. Demonstrations of both how to evaluate the actual
      probative value of evidence (when all necessary values are known), and the
      theoretical limit of its probative value (in circumstances where some values are
      not known) are provided. It is argued that such evaluations may provide the basis
      for (1) support of motions to either admit or to exclude evidence, (2) testimony
      to the jury to help them weigh or interpret evidence, (3) exculpatory profiling
      (profiling evidence of innocence), (4) pretrial research to establish probative
      versus prejudicial value of evidence, and (5) sufficiency analyses to determine
      maximum likelihood of guilt, given multiple items of evidence. Among these, the
      first two are considered most important, as it can be demonstrated that many
      "profiling" characteristics currently admitted in trial (such as evidence of
      battery to support a murder charge) are not probative of guilt.

PMID- 11985296
TI  - Forecasting trial outcomes: lawyers assign higher probability to possibilities
      that are described in greater detail.
AB  - The study of judgment under uncertainty has revealed that people judge the
      probability of an event to be higher when the event is described as a disjunction
      of constituent events or when they judge constituent events separately. These
      observations have motivated the development of support theory (Y. Rottenstreich &
      A. Tversky, 1997; A. Tversky & D. J. Koehler, 1994), a descriptive model of
      judgment under uncertainty. The major predictions of support theory are that (1)
      the judged probabilities of complementary events sum to 1; (2) the judged
      probabilities of n > 2 exclusive and exhaustive events generally sum to more than
      1; and (3) the judged probability of an event generally increases when it is
      described as a disjunction of specific possibilities. We test these predictions
      in 6 studies of experienced attorneys who judged the likelihood of particular
      trial outcomes or were asked to offer advice on whether or not to accept a
      settlement offer. The results demonstrate that attorneys are indeed susceptible
      to bias in forecasting trial outcomes, consistent with support theory.

PMID- 11985297
TI  - The role of death qualification in venirepersons' evaluations of aggravating and
      mitigating circumstances in capital trials.
AB  - Previous research has found that death qualification impacts jurors'
      receptiveness to aggravating and mitigating circumstances (e.g., J. Luginbuhl &
      K. Middendorf, 1988). However, the purpose of this study was to investigate
      whether death qualification affects jurors' endorsements of aggravating and
      mitigating circumstances when Witt, rather than Witherspoon, is the legal
      standard for death qualification. Four hundred and fifty venirepersons from the
      11th Judicial Circuit in Miami, Florida completed a booklet of stimulus materials
      that contained the following: two death qualification questions; a case scenario
      that included a summary of the guilt and penalty phases of a capital case; a 26
      item measure that required participants to endorse aggravators, nonstatutory
      mitigators, and statutory mitigators on a 6-point Likert scale; and standard
      demographic questions. Results indicated that death-qualified venirepersons, when
      compared to excludables, were more likely to endorse aggravating circumstances.
      Excludable participants, when compared to death-qualified venirepersons, were
      more likely to endorse nonstatutory mitigators. There was no significant
      difference between death-qualified and excludable venirepersons with respect to
      their endorsement of 6 out of 7 statutory mitigators. It would appear that the
      Gregg v. Georgia (1976) decision to declare the death penalty unconstitutional is
      frustrated by the Lockhart v. McCree (1986) affirmation of death qualification.

PMID- 11985298
TI  - Effects of social support on children's eyewitness reports: a test of the
      underlying mechanism.
AB  - Research on children's eyewitness testimony demonstrates that interviewer
      provided social support given during a mock forensic interview helps children
      resist an interviewer's misleading suggestions about past events. We proposed and
      tested 1 potential mechanism underlying support effects: "Resistance Efficacy,"
      or children's perceived self-efficacy for resisting an interviewer's suggestions.
      Eighty-one 6- and 7-year-old children experienced a play event, then were
      interviewed about the event with misleading and specific questions. Consistent
      with prior research, children interviewed by a supportive person were more
      resistant to misleading suggestions than were those interviewed by a
      nonsupportive person. Although Resistance Efficacy did not mediate the effects of
      interviewer support in the full sample, additional analyses revealed that
      Resistance Efficacy may be a mediator for older, but not younger, children.
      Contrary to predictions, children's preexisting social support reserves were not
      related to children's interview accuracy nor to perceived Resistance Efficacy.
      Implications for psychological theory are discussed, as well as implications for
      understanding and improving children's eyewitness reports.

PMID- 11985299
TI  - Adolescent development and the measurement of juvenile psychopathy.
AB  - Researchers are currently seeking antecedents of psychopathy among children and
      adolescents. Instruments developed for this purpose are likely to be used in the
      future in ways that may have serious implications for youths in delinquency and
      criminal cases. In this regard, and because the concept and measurement of
      psychopathy have been developed in reference to adults, there is reason to be
      concerned about potential developmental sources of false positives when measuring
      psychopathic traits in juvenile offenders. We provide the basis for our concern,
      as well as standards regarding the types of research evidence that should be
      provided before psychopathy measures are accepted for use in juvenile forensic
      assessments.

PMID- 11985300
TI  - Commentary on Seagrave and Grisso: impressions of the state of the art.
AB  - Seagrave and Grisso (2001) questioned the clinical-forensic utility of tests
      designed to assess juvenile psychopathy. They discussed potential problems with
      such tests and some avenues for future research. We agree with the points made by
      Seagrave and Grisso, but believe their critique did not go far enough. The "state
      of the art" with respect to the assessment of juvenile psychopathy is like an
      Impressionist painting: fine from a distance; but the closer you get, the messier
      it looks. We conclude that although tests of "juvenile psychopathy" measure
      something, it is impossible to be sure at this time they are actually measuring
      psychopathy.

PMID- 11985301
TI  - Juvenile psychopathy from a developmental perspective: implications for construct
      development and use in forensic assessments.
AB  - D. Seagrave and T. Grisso (2002) provide a review of the emerging research on the
      construct of juvenile psychopathy and make the important point that use of this
      construct in forensic decision-making could have serious consequences for
      juvenile offenders. Furthermore, the existing literature on the construct of
      psychopathy in youth is not sufficient to justify its use for most forensic
      purposes. These basic points are very important cautions on the use of measures
      of psychopathy in forensic settings. However, in this response, several issues
      related to the reasons given for why concern over the potential misuse of
      measures of psychopathy should be greater than that for measures of other
      psychopathological constructs used to make decisions with potentially serious
      consequences are discussed. Also, the rationale for some of the standards
      proposed to guide research on measures of juvenile psychopathy that focus on
      assumptions about the construct of psychopathy that are not clearly articulated
      and that are only peripherally related to validating their use in forensic
      assessments is questioned.

PMID- 11985302
TI  - Fledgling psychopathy: a view from personality theory.
AB  - Although the author agrees with Seagrave and Grisso that the research base does
      not yet support the use of extant measures of juvenile psychopathy in forensic
      settings, he disagrees with the general pessimism of Seagrave and Grisso
      regarding the assessment of juvenile psychopathy. The author argues that data
      drawn from basic research in personality argues against the concern that
      normative development changes will cloud the assessment of psychopathy.
      Additionally, the present author argues that fledgling psychopathy holds the key
      to successful intervention.

PMID- 11985303
TI  - Manipulating chemoattractant and receptor genes.
AB  - Chemoattractants, including classical chemotactic factors and members of the
      chemokine superfamily, function as inducers of leukocyte trafficking and
      activation based on interactions with seven transmembrane (STM), G protein
      coupled receptors. These molecules are expressed by many cell types either
      constitutively or upon stimulation. Considerable knowledge about the
      pathophysiological role of chemoattractants and their receptors has been
      accumulated during the past two decades. However, recent studies using transgenic
      and gene targeting technology have provided a better illustration of the
      importance and complexity of the involvement of chemoattractants and receptors in
      leukocyte trafficking, inflammation, infection, immune responses, development,
      angiogenesis/angiostasis, and malignant tumors.

PMID- 11985304
TI  - Multiplexed gene expression analysis using the invader RNA assay with MALDI-TOF
      mass spectrometry detection.
AB  - A mass spectrometric approach for measuring gene expression levels has been
      developed. This technique utilizes a signal amplification system and analysis by
      matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry. Signal amplification from the targeted RNA employs a recently
      developed invasive cleavage assay that does not require prior PCR amplification.
      The assay uses a set of target-specific probes (oligonucleotides), which
      hybridize to the RNA being measured to create an overlap structure with a single
      stranded flap. This flap is enzymatically cleaved and accumulates linearly in a
      target-specific manner. The products of the reaction, short DNA oligomers, are
      well suited for quantitative detection by MALDI-TOF mass spectrometry.
      Multiplexing is achieved by designing the assays so that reaction products for
      different mRNA targets have discrete masses that can be resolved in a single mass
      spectrum. Simultaneous analysis of human cytokine in vitro transcripts IL-1beta,
      TNF-alpha, and IL-6, with GAPDH as a reference standard, was used as a model
      system to demonstrate this novel method of gene expression analysis.

PMID- 11985305
TI  - A simplified broadband coupling approach applied to chemically robust sol-gel,
      planar integrated optical waveguides.
AB  - A new generation waveguide spectrometer with broadband coupling capabilities has
      been developed. As opposed to previous devices, this attenuated total reflection
      (ATR) spectrometer is much simpler in design, is more chemically robust, and
      transmits light down to at least 400 nm. The attenuated total reflection element
      consists of a single-mode, planar integrated optical waveguide fabricated by dip
      coating a approximately 300 nm thick, sol-gel composite layer on a glass
      substrate. A commercially available prism is used as the incoupler with an
      integral holographic diffraction grating acting as the dispersive outcoupling
      element. The transmission of narrow band-pass filters was used to compare the
      response of the waveguide spectrometer to that of a conventional transmission
      instrument. Spectral resolution was assessed by measuring the fwhm of various
      laser lines, which were found to range from 0.5 to 1.3 nm. The measured limits of
      detection for the waveguide spectrometer from 400 to 600 nm are 8.0 and 10.1
      milliabsorbance units for TE and TM polarizations, respectively. Finally, to
      demonstrate the application of this technology to a molecular film confined to a
      solid-liquid interface, visible ATR spectra of an adsorbed submonolayer of horse
      heart cytochrome c were acquired. A procedure to correct the waveguide spectra
      for the wavelength dependence in ATR path length is described.

PMID- 11985306
TI  - Protein identification by MALDI-TOF-MS peptide mapping: a new strategy.
AB  - A new strategy for identifying proteins by MALDI-TOF-MS peptide mapping is
      reported. In contrast to current approaches, the strategy does not rely on a good
      relative or absolute mass accuracy as the criterion that discriminates false
      positive results. The protein sequence database is first searched for all
      proteins that match a minimum five of the submitted masses within the maximum
      expected relative errors when the default or externally determined calibration
      constants are used, for instance, +/-500 ppm. Typically, this search retrieves
      many thousand candidate sequences. Assuming initially that each of these is the
      correct protein, the relative errors of the matching peptide masses are
      calculated for each candidate sequence. Linear regression analysis is then
      performed of the calculated relative errors as a function of m/z for each
      candidate sequence, and the standard deviation to the regression is used to
      distinguish the correct sequence among the candidates. We show that this
      parameter is independent of whether the mass spectrometric data were internally
      or externally calibrated. The result is a search engine that renders internal
      spectrum calibration unnecessary and adapts to the quality of the raw data
      without user interference. This is made possible by a dynamic scoring algorithm,
      which takes into account the number of matching peptide masses, the percentage of
      the protein's sequence covered by these peptides and, as new parameter, the
      determined standard deviation. The lower the standard deviation, the less
      cleavage peptides are required for identification and vice versa. Performance of
      the new strategy is demonstrated and discussed. All necessary computing has been
      implemented in a computer program, free access to which is provided in the
      Internet.

PMID- 11985307
TI  - A prototype two-dimensional capillary electrophoresis system fabricated in
      poly(dimethylsiloxane).
AB  - A method for carrying out 2D gel electrophoresis in a capillary format is
      presented. In this method, separation in the first dimension is carried out in a
      1D capillary, with this system physically isolated from the capillaries that
      provide the separation in the second dimension. After completion of the first
      separation, the 1D channel is physically connected to the 2D capillaries, and a
      second separation is carried out in an orthogonal set of parallel capillaries.
      The ability of poly(dimethylsiloxane) (PDMS) to support the fabrication of 3D
      microfluidic systems makes it possible to produce membranes that both enclose the
      gel used in the first separation in a capillary and provide passages for the
      proteins to migrate into the array of orthogonal capillaries. The elastomeric
      nature of PDMS makes it possible to make reversible connections between pieces of
      PDMS. The feasibility of this system is demonstrated using a protein mixture
      containing fluorescein-conjugated carbonic anhydrase, fluorescein-conjugated BSA,
      and Texas Red-conjugated ovalbumin. This work suggests one type of design that
      might form the basis for a microfabricated device for 2D capillary
      electrophoresis.

PMID- 11985308
TI  - A 2-D liquid separations/mass mapping method for interlysate comparison of
      ovarian cancers.
AB  - A two-dimensional liquid phase separation of proteins from whole cell lysates
      coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass
      spectrometer (MS) is used to map the protein content of ovarian surface
      epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two
      dimensions involve the use of liquid isoelectric focusing as the first phase and
      nonporous silica reversed-phase HPLC as the second phase of separation. Accurate
      molecular weight (MW) values are then obtained upon the basis of ESI-TOFMS so
      that an image of isolectric point (pI) versus MW analogous to 2-D gel
      electrophoresis is produced. The accurate MW together with the pI fraction and
      corresponding hydrophobicity (%B) are used to tag each protein so that protein
      expression can be compared in interlysate studies. Each protein is also
      identified on the basis of matrix-assisted laser desorption-ionization (MALDI)
      TOFMS peptide mapping and intact MW so that a standard map is produced against
      which other cell lines can be compared. Quantitative changes in protein
      expression are measured in these interlysate comparisons using internal standards
      in the on-line ESI-TOFMS process. In the ovarian epithelial cell lines under
      study, it is shown that in the three pI fractions chosen for detailed analysis,
      over 50 unique proteins can be detected per fraction, of which 40% can be
      identified from web-based databases. It is also shown that when using an accurate
      MW to compare proteins in the OSE versus ovarian cancer sample, there are
      proteins highly expressed in cancer cells but not in normal cells. In addition,
      many of the proteins in the cancer sample appear to be down-regulated, as
      compared to the normal cells. This two-dimensional (2-D) liquid/mass mapping
      method may provide a means of studying proteins in interlysate comparisons not
      readily available by other methods.

PMID- 11985309
TI  - High-sensitivity detection of DNA hybridization on microarrays using resonance
      light scattering.
AB  - The application of resonance light scattering (RLS) particles for high
      sensitivity detection of DNA hybridization on cDNA microarrays is demonstrated.
      Arrays composed of approximately 2000 human genes ("targets") were hybridized
      with colabeled (Cy3 and biotin) human lung cDNA probes at concentrations ranging
      from 8.3 ng/microL to 16.7 pg/microL. After hybridization, the arrays were imaged
      using a fluorescence scanner. The arrays were then treated with 80-nm-diameter
      gold RLS Particles coated with anti-biotin antibodies and imaged in a white
      light, CCD-based imaging system. At low probe concentrations, significantly more
      genes were detected by RLS compared to labeling by Cy3. For example, for
      hybridizations with a probe concentration of 83.3 pg/microL, approximately 1150
      positive genes were detected using RLS compared to approximately 110 positive
      genes detected with Cy3. In a differential gene expression experiment using human
      lung and leukemia RNA samples, similar differential expression profiles were
      obtained for labeling by RLS and fluorescence technologies. The use of RLS
      Particles is particularly attractive for detection and identification of low
      abundance mRNAs and for those applications in which the amount of sample is
      limited.

PMID- 11985310
TI  - Cell lysis and protein extraction in a microfluidic device with detection by a
      fluorogenic enzyme assay.
AB  - A critical requirement for achieving a micro total analytical system for the
      analysis of cells and their constituent proteins is to integrate the lysis and
      fractionation steps on-chip. Here, an experimental microfluidic system
      integrating the lysis of bacterial cells and the extraction of a large
      intracellular enzyme, beta-galactosidase, is demonstrated. The beta-galactosidase
      is detected and quantified using a fluorogenic enzyme assay and a numerical
      model. While the focus is on the lysis of typical gram-negative bacterial cells
      (E. coli), the techniques described here could, in principle, be applied to a
      variety of different cell types.

PMID- 11985311
TI  - Arrays of self-assembled monolayers for studying inhibition of bacterial
      adhesion.
AB  - This paper describes a simple and convenient method for the rapid screening of
      potential inhibitors of bacterial adhesion and for the quantitative evaluation of
      the efficacy of the inhibitors using arrays of self-assembled monolayers (SAMs)
      of alkanethiolates on gold that are presented on a 96-well microtiter plate. The
      SAMs present mixtures of alpha-D-mannopyranoside (a ligand that promotes the
      adhesion of uropathogenic Escherichia coli by binding to the FimH proteins on the
      tip of type 1 pili), and tri(ethylene glycol) moieties (organic groups that
      resist nonspecific adsorption of proteins and cells). The SAMs provide surfaces
      for studies of adhesion of uropathogenic E. coli to specific ligands; they also
      provide excellent resistance to nonspecific adhesion. Using arrays of mannoside
      presenting SAMs, inhibitors of bacterial adhesion were easily screened by
      observing the number of bacteria that adhered to the surface of the SAMs in the
      presence of inhibitor. The potency of the inhibitor was quantified by measuring
      the percentage of inhibition as a function of the concentration of the inhibitor.
      The properties of SAMs, when combined with the convenience and standardization of
      a microtiter plate, make arrays of SAMs a versatile tool that can be applied to
      high-throughput screening of inhibitors of bacterial, viral, and mammalian cell
      adhesion and of strongly binding ligands for proteins.

PMID- 11985312
TI  - Imaging solute distribution in capillary electrochromatography with laser
      scanning confocal microscopy.
AB  - A method for the direct observation of solute molecules interacting with a C18
      stationary phase under real separation conditions in capillary
      electrochromatography (CEC) is investigated. The experiments were performed in a
      capillary electrochromatographic mode; however, the method and findings are
      useful both in CEC and revered-phase liquid chromatography. The distribution of
      solute molecules in the packed capillary is directly imaged with laser scanning
      confocal fluorescence microscopy. Conventional imaging techniques produce images
      where the C18 silica beads cannot be distinctively identified as a result of the
      deep depth of field. The optical sectioning capability of confocal imaging
      overcomes this problem to afford clearly defined images of the stationary-phase
      packing and the surrounding mobile phase. Fluorescein molecules are
      preferentially distributed in the mobile phase under reversed-phase
      chromatographic conditions. Nile Red and rhodamine 6G molecules prefer the
      environments of the porous C18 beads. Intensity distributions over time for areas
      within the stationary-phase beads differ from distributions of areas outside the
      beads in the mobile phase. Images taken at different depths into the capillary
      probe the internal structure of the C18 beads. While the internal structures of
      most beads are porous, confocal images show a small fraction (2%) of the silica
      beads have porous shells and nonporous cores. The capability of imaging the
      stationary phase distinctively from the mobile phase opens the possibilities of
      studying the quality of stationary phase, the structure of the column packing,
      and the mechanisms of separation.

PMID- 11985313
TI  - In situ time-resolved fluorescence spectroscopy in the frequency domain in
      capillary electrochromatography.
AB  - In situ time-resolved fluorescence spectroscopy for capillary
      electrochromatography (CEC) is described in the frequency domain. Fluorescence
      decay of the solute molecules is collected directly in the packed stationary
      phase of the CEC capillary. The fluorescence lifetime profile of the solute
      molecules reveals the microenvironments they experience in the C18
      chromatographic interface. A quartz flow cell and experimental optimization of
      the signal-to-noise ratio are described that enable the collection of high
      quality decay data and subsequent calculation of fluorescence lifetime profiles
      of the solute molecules. The distribution of pyrene (PY), 1-pyrenemethanol (PY
      MeOH), and 1-pyrenebutanol (PY-BuOH) into the C18 stationary phase and the solute
      C18 phase interactions are probed, under separation conditions for CEC. All three
      molecules display a Gaussian distribution of lifetimes, consistent with an
      ensemble of heterogeneous microenvironments in the C18 stationary phase. The
      least polar molecule PY diffuses deeply into and interacts extensively with the
      C18 phase, experiencing high hydrophobicity and significant heterogeneity of
      microenvironments. The retention order of PY-MeOH, PY-BuOH, and PY in CEC is
      determined by their interactions with the stationary phase, revealed by their
      fluorescence lifetime distributions.

PMID- 11985314
TI  - Interpretation of static time-of-flight secondary ion mass spectra of adsorbed
      protein films by multivariate pattern recognition.
AB  - Multivariate analysis has become increasingly common in the analysis of
      multidimensional spectral data. We previously showed that the multivariate
      analysis technique principal component analysis (PCA) is an excellent method for
      interpreting the static time-of-flight secondary ion mass spectrometry (TOF-SIMS)
      spectra of adsorbed protein films. PCA is an unsupervised pattern recognition
      technique that loses resolution between spectra of different proteins as more
      proteins are added to the data set due to large within-group variation. The
      supervised pattern recognition techniques discriminant principal component
      analysis (DPCA) and linear discriminant analysis (LDA), which aim to control
      within-group variation while maximizing between-group separation to enhance
      discrimination between groups, were compared with PCA using data sets of TOF-SIMS
      spectra of proteins adsorbed onto mica and PTFE substrates. DPCA and LDA
      quantitatively improved discrimination between groups and provided different
      information about the data than PCA. LDA was able to classify unknown samples
      with a misclassification rate lower than PCA or DPCA. Both unsupervised and
      supervised pattern recognition techniques are useful for the interpretation and
      classification of static TOF-SIMS spectra of adsorbed protein films.

PMID- 11985315
TI  - High-density fiber-optic genosensor microsphere array capable of zeptomole
      detection limits.
AB  - The detection limit of a fiber-optic microsensor array was investigated for
      simultaneous detection of multiple DNA sequences. A random array composed of
      oligonucleotide-functionalized 3.1-microm-diameter microspheres on the distal
      face of a 500-microm etched imaging fiber was monitored for binding to
      fluorescently labeled complementary DNA sequences. Inherent sensor redundancy in
      the microarray allows the use of multiple microspheres to increase the signal-to
      noise ratio, further enhancing the detection capabilities. Specific hybridization
      was observed for each of three sequences in an array yielding a detection limit
      of 10(-21) mol (approximately 600 DNA molecules).

PMID- 11985316
TI  - Electrochemical imaging of diffusion through single nanoscale pores.
AB  - A combined scanning electrochemical-atomic force microscope (SECM-AFM) has been
      used to probe the diffusional transport of target electroactive solutes in
      isolated nanopores of a track-etched membrane. A polycarbonate membrane (100-nm
      diam pore size) hydrated with an electrolyte solution, containing a redox-active
      probe molecule, such as IrCl6(3-) or Fe(phen)3(2+), functions as the model
      membrane system. The use of a mobile Pt-coated AFM probe enables individual
      solution-filled pores to be topographically identified. Analysis of the
      corresponding current images for the diffusion-limited oxidation of the redox
      mediator indicates that solution is largely confined to pores in the membrane.
      Moreover, the tip collector current response provides information on diffusion of
      the mediator through the pore. Force-distance tip approach and retract
      measurements allow the radius of contact between the electrochemical-AFM tip and
      solution confined within a pore at the point of pull-off to be estimated.

PMID- 11985317
TI  - Rapid enumeration of respiratory viruses.
AB  - Virus detection and enumeration has become increasingly important in fields
      ranging from medicine and biotechnology to environmental science. Although there
      are a wide variety of techniques that can be used to count viruses, there is
      demand for a rapid and more accurate means for virus enumeration. In this work,
      the performance of a flow cytometer that was designed and custom-built
      specifically for rapid detection of single viruses was evaluated. The instrument,
      designated a single nanometric particle enumerator (SNaPE), was characterized and
      calibrated using fluorescent polystyrene nanospheres. The reliability of the
      instrument with respect to virus enumeration was demonstrated for three medically
      relevant viruses, adenovirus-5, respiratory syncytial virus, and influenza A,
      treated with a fluorescent nucleotide stain. In each case, the SNaPE yielded a
      virus particle concentration consistent with, but slightly lower than,
      transmission electron microscopy (TEM) results, as expected. In addition, on the
      basis of calibration of signal intensity, the average peak height for a given
      virus was correlated with genome size, as expected. In contrast to time-consuming
      analyses such as TEM and plaque titers, SNaPE analysis of pure virus samples
      (including sample handling, data collection, and data processing) can be
      completed within 1 h.

PMID- 11985318
TI  - Electrophoretic profiling of both RNA and protein from a single 250-pL sample.
AB  - A novel approach is described that uses capillary electrophoresis (CE) to
      electrophoretically sample and separate both protein and RNA from a single
      injected plug of cell lysate. A 250-pL sample of lysate from Chinese hamster
      ovary cells (9.6 x 10(7) cells/mL) was hydrodynamically injected into a capillary
      containing a Tris-based aqueous buffer. This was followed by selective
      electrokinetic ejection of RNA from the lysate into water, yielding an effective
      cell concentration of RNA of 3000 cells/mL. The cellular components (e.g.,
      proteins) retained in the capillary were separated and then detected with laser
      induced fluorescence (LIF) using 275-nm excitation. The ejected/diluted sample
      was subsequently injected into a separate CE-LIF system, which utilized an
      entangled polymer sieving matrix and 543-nm excitation for the detection of
      ethidium bromide-labeled nucleic acids (i.e., RNA). Virtually no sample
      preparation is required other than simple washing and lysing of the cells
      isolated from culture. This combined approach can be easily modified for the
      detection of any analyte through adjustment of CE-HF conditions. In addition, it
      provides an effective method for desalting cellular RNA samples having complex
      matrixes, which results in improved RNA injection efficiency and a 7600-fold
      effective signal enhancement over total lysate injection.

PMID- 11985319
TI  - Polymerase chain reaction amplification of DNA from aged blood stains:
      quantitative evaluation of the "suitability for purpose" of four filter papers as
      archival media.
AB  - In collaboration with the Armed Forces Institute of Pathology's Department of
      Defense DNA Registry, the National Institute of Standards and Technology recently
      evaluated the performance of a short tandem repeat multiplex with dried whole
      blood stains on four different commercially available identification card
      matrixes. DNA from 70 stains that had been stored for 19 months at ambient
      temperature was extracted or directly amplified and then processed using routine
      methods. All four storage media provided fully typeable (qualitatively identical)
      samples. After standardization, the average among-locus fluorescence intensity
      (electropherographic peak height or area) provided a suitable metric for
      quantitative analysis of the relative amounts of amplifiable DNA in an archived
      sample. The amounts of DNA in Chelex extracts from stains on two untreated high
      purity cotton linter pulp papers and a paper treated with a DNA-binding coating
      were essentially identical. Average intensities for the aqueous extracts from a
      paper treated with a DNA-releasing coating were somewhat lower but also somewhat
      less variable than for the Chelex extracts. Average intensities of directly
      amplified punches of the DNA-binding paper were much larger but somewhat more
      variable than the Chelex extracts. Approximately 25% of the observed variation
      among the intensity measurements is shared among the four media and thus can be
      attributed to intrinsic variation in white blood count among the donors. All of
      the evaluated media adequately "bank" forensically useful DNA in well-dried whole
      blood stains for at least 19 months at ambient temperature.

PMID- 11985320
TI  - Analysis by capillary electrophoresis of the kinetics of charge ladder formation
      for bovine carbonic anhydrase.
AB  - A series of charge ladders of bovine carbonic anhydrase II were synthesized and
      the relative abundances of the rungs analyzed by capillary electrophoresis as a
      function of the quantity of acylating agent used. A simulation that models the
      kinetics of formation of the members of the charge ladders is described. The
      observed rate constants decreased as the extent of acylation increased. These
      rate constants correlated adequately with theoretical rate constants calculated
      using Debye-Huckel theory. The data are compatible with, but do not demand, a
      model for the formation of this charge ladder in which all unacetylated amino
      groups in each rung have indistinguishable reactivity and in which the reactivity
      of the amines in each rung decreases as the net charge on the protein increases;
      in this model, decreased reactivity is due to increased extent of protonation.
      This agreement between experiment and model suggests that the charge shielding
      that results from an ionic strength of 130 mM is not sufficient to suppress the
      influence of the increasingly negative charge of the protein with acetylation on
      the extent of protonation of Lys epsilon-NH2 groups.

PMID- 11985321
TI  - Composition of explosives by electrospray ionization Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - Commercial explosives are complex mixtures that contain not only the active
      explosive agent(s) but also a host of other organic and inorganic compounds. The
      ultrahigh mass resolving power (m/delta m50% >200,000) and mass accuracy (<1 ppm)
      of electrospray ionization Fourier transform ion cyclotron resonance (ESI FTICR)
      mass spectrometry allow for definitive identification of various species in TNT,
      RDX, and HMX. We are thereby able to correct prior misassignments of the
      elemental compositions of the most abundant negative ions from electrospray of
      RDX and HMX. Although the (known) active agents of many explosives may be
      identified by low-resolution MS or MS/MS, it is the other characteristic
      components (indigenous or artificial additives) whose presence and elemental
      composition can potentially identify the source of the product. ESI FTICR mass
      spectrometry of smokeless powder, TNT, and Powermite resolves and identifies
      numerous nonactive ingredients, many of which are recovered in a postblast
      residue. In contrast, the residue recovered from an explosion of military C4
      yielded several species derived from RDX but virtually none from other
      ingredients.

PMID- 11985322
TI  - Optimization of guanidination procedures for MALDI mass mapping.
AB  - Improved procedures for guanidination of lysine-containing peptides, a
      derivatization that results in increased MALDI mass spectral signal intensities
      are presented. The complete conversion of lysines to homoarginines can be
      accomplished in as little as 5 min. The method is demonstrated on a model peptide
      and on tryptic digests of three proteins. To demonstrate the applicability to
      proteomics samples, it is successfully applied to the digest of 50 fmol of a
      protein. Approaches for concentrating and purifying low-quantity protein digests
      following guanidination are evaluated. Experiments with the model peptide GRGDSPK
      enable investigation of the specificity of the guanidination reaction.

PMID- 11985323
TI  - Atmospheric pressure matrix-assisted laser desorption/ionization in transmission
      geometry.
AB  - In both atmospheric pressure matrix-assisted laser desorption/ionization (AP
      MALDI) and vacuum MALDI, the laser typically illuminates the analyte on the front
      side of an opaque surface (reflection geometry). Another configuration consisting
      of laser illumination through the sample backside (transmission geometry) has
      been used in conventional MALDI; however, its use and the number of reports in
      the literature are limited. The viability of transmission geometry with AP MALDI
      is demonstrated here. Such a geometry is simple to implement, eliminates the
      restriction for a metallic sample holder, and allows for the potential analysis
      of samples on their native transparent surfaces, e.g., cells or tissue sections
      on slides.

PMID- 11985324
TI  - An evaluation of a four-channel multiplexed electrospray tandem mass spectrometry
      for higher throughput quantitative analysis.
AB  - A four-channel multiplexed electrospray inlet system (MUX) coupled to a triple
      quadrupole mass spectrometer was investigated as a higher throughput approach to
      quantitative analysis. Four discrete samples may be simultaneously analyzed by
      virtue of a rotating sampler with a concomitant 4-fold increase in analytical
      throughput. Although absolute sensitivity was reduced using the MUX interface
      compared with analysis using traditional single electrospray interface,
      reproducibility of response was shown to be comparable. Source robustness was
      established for the analysis of both aqueous drug standards and drugs in
      biological media, and linearity of response for a test compound, diazepam, was
      demonstrated over 2 orders of magnitude. Analyte-dependent response differences
      were exhibited between the four channels of the interface, and this led to the
      overall conclusion that samples to be compared quantitatively must be analyzed
      through the same sprayer. In addition, each channel must be independently
      calibrated to afford true quantification. Should a deuterated internal standard
      be employed, however, quantitative comparisons can be made across channels. An
      HPLC pumping system providing individual back-pressure regulation to each channel
      was shown to provide adequate chromatography even in the event of a channel
      blockage. Furthermore, following multiple injections of biological samples onto
      the MUX interface, an eluent flow diversion was integrated into the first part of
      each analytical run. This served to prevent source fouling, and thus, no
      detrimental effects to response reproducibility or sensitivity were observed.

PMID- 11985325
TI  - Affinity capillary electrophoresis using a low-concentration additive with the
      consideration of relative mobilities.
AB  - Most affinity studies in capillary electrophoresis assume that the analyte
      concentration is much smaller than the additive concentration so that the
      migration of the analyte has no effect on the concentration of the additive in
      the capillary. However, in most medium- to high-affinity interactions, the
      additive concentration has to be kept rather low to observe the changes in
      analyte mobility before saturation is reached. In this paper, a mathematical
      model is developed to describe the migration behavior of the analyte in a system
      where the complex formed becomes concentrated to levels much greater than the
      original concentration of the additive due to the differences in the mobilities
      of the analyte, additive, and complex. The analyte is flurbiprofen, the additive
      is transthyretin, and the stoichiometry of the reaction between the two is 1:2.
      This study also provides a new algorithm to determine medium- to high-affinity
      binding interaction constants by CE.

PMID- 11985326
TI  - A protein-encapsulation technique by the sol-gel method for the preparation of
      monolithic columns for capillary electrochromatography.
AB  - A novel protein-encapsulation technique using sol-gels was developed for the
      preparation of monolithic capillary columns for capillary electrochromatography.
      Two chiral compounds, bovine serum albumin (BSA) and ovomucoid (OVM) from chicken
      egg white, were encapsulated in tetramethoxysilane-based hydrogel and their
      chiral selectivity was evaluated for the separation of some selected enantiomers
      (tryptophan, benzoin, eperisone, chlorpheniramine). The protein encapsulation was
      carried out within a capillary in a single step under mild conditions. The
      resultant monolithic columns showed adequate chromatographic performance,
      including mechanical strength, penetration of pressurized flow, and chiral
      separation. Two different proteins, BSA and OVM, were successfully encapsulated
      into the gel matrixes by changing the alkoxysilane compositions of the gel. Run
      to-run repeatability was quite satisfactory. The consecutive analysis of the
      neutral compound, benzoin, by the OVM-encapsulated column showed good
      repeatability in the retention time (RSD = 1.23% for the first peak, N = 10).
      Under optimized conditions, the theoretical plate number for the first peak of
      benzoin reached 72,000 plates/m.

PMID- 11985327
TI  - Development and validation of spectroscopic methods for monitoring density
      changes in pressurized gaseous and supercritical fluid systems.
AB  - The further development of new processes utilizing liquid or supercritical CO2 as
      a solvent will benefit from the rational design of new CO2-philes. Understanding
      solvation structures and mechanisms of these molecules is an important part of
      this process. In such studies, determining the change in density as a function of
      the measured thermodynamic conditions (pressure and temperature) provides an
      excellent means of directly monitoring the solution conditions in the detection
      volume for a given technique. By integrating spectroscopic peaks, changes in area
      can be used to determine changes in analyte concentration in the detection
      volume, and thus, it should be possible to monitor the system density in situ. In
      the present study, we examine the utility of Raman and NMR spectroscopy as a
      means of following changes in solution density conditions and validate this
      approach in pure fluids and gases (N2 and CO2) and supercritical fluid mixtures
      (acetaldehyde vapor in N2). In addition, we present the design of a simple,
      inexpensive cell for conducting Raman and NMR measurements under moderate
      pressure conditions.

PMID- 11985328
TI  - Temperature gradient interaction chromatography and MALDI-TOF mass spectrometry
      analysis of stereoregular poly(ethyl methacrylate)s.
AB  - Temperature gradient interaction chromatography (TGIC) was applied for the
      separation of stereoregular poly(ethyl methacrylate) (PEMA) according to the
      tacticity. The three PEMA samples with differing tacticity (rr triad content 0,
      53, and 91%) prepared by anionic polymerization were used. C18 bonded silica and
      a mixture of CH2Cl2 and CH3CN (30/70, v/v) were used as stationary and mobile
      phase, respectively. TGIC was able to separate the PEMA samples, showing the
      increasing retention in the order of decreasing rr triad contents; however TGIC
      elution peaks of the three PEMAs were not fully resolved but, rather, were
      partially overlapped. To isolate the tacticity effect from the molecular weight
      effect on the TGIC retention, the PEMA samples were fractionated by TGIC, and the
      accurate molecular weight of the fractions was determined by MALDI-TOF mass
      spectrometry. The fractions showed a much narrower molecular weight distribution
      than the mother PEMAs. The TGIC fractions of similar molecular weight but with
      different tacticity were fully resolved by TGIC, but mother PEMAs were not. These
      results indicate that the retention in TGIC is affected by both tacticity and
      molecular weight.

PMID- 11985329
TI  - Resveratrol, a natural chemopreventive agent against degenerative diseases.
AB  - Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring compound shown
      to modulate the risk of cardiovascular degenerative diseases (atherosclerosis)
      and inhibit chemical carcinogenesis in rodents. Various studies have demonstrated
      the effect of this phytoalexin on biological mechanisms involved in
      cardioprotection. These include modulation of lipid turnover, inhibition of
      eicosanoid production, prevention of the low-density lipoprotein oxidation and
      inhibition of platelet aggregation. Carcinogenesis in animal models can be
      divided at least into three stages: initiation, promotion and progression.
      Initiation occurs as result of interaction of a reactive form of carcinogen with
      DNA. Chemical carcinogens like polycyclic aromatic hydrocarbons are metabolized
      to reactive species by cytochrome P450 dependent enzymes activated through aryl
      hydrocarbon (Ah) receptor. The inhibition of tumor initiation by resveratrol most
      probably occurs through preventing the activation of Ah receptor. Resveratrol
      affects also several factors involved in tumor promotion and progression. Since
      tumor promoting agents alter the expression of genes whose products are
      associated with inflammation, chemoprevention of cardiovascular diseases and
      cancer may share the same common mechanisms. This includes principally modulation
      of the expression of growth factors and cytokines. Recently, chemopreventive
      properties of resveratrol have been associated with the inhibition of NF-kappaB.
      This transcription factor is strongly linked to inflammatory and immune
      responses, regulation of cell proliferation and apoptosis, thus it is important
      for tumor development and many other diseases including atherosclerosis. Although
      the mechanisms by which resveratrol interferes with the activation of NF-KB are
      not clear, it seems that inhibition of its degradation which is necessary for its
      cellular activation is the principal target. Based on the quantity and diversity
      of data available on the biological activity of resveratrol, it has to be
      considered a very promising chemoprotector and chemotherapeutic. Urgent
      investigations on its bioavailability and effects on in vivo systems, especially
      in humans, are necessary.

PMID- 11985330
TI  - Repeated imipramine treatment enhances the 7-OH-DPAT-induced hyperactivity in
      rats: the role of dopamine D2 and D3 receptors.
AB  - Previous studies have shown that antidepressant drugs with different
      pharmacological profiles, administered repeatedly, increase the locomotor
      hyperactivity induced by various dopaminomimetics, among others by (+/-)7
      hydroxydipropylaminotetralin (7-OH-DPAT). Since, according to a recent study,
      this drug shows a high affinity for not only dopamine D3 but also dopamine D2
      receptors, a question arises whether dopamine D3 receptors are involved in the
      increase in 7-OH-DPAT-elicited locomotor hyperactivity induced by repeated
      treatment with antidepressant drugs. The aim of the present study was to
      investigate the effect of imipramine (IMI), administered repeatedly, on the
      hyperactivity induced by 7-OH-DPAT, a dopamine D3 receptor-preferring agonist.
      Male Wistar rats were treated with IMI (10 mg/kg po) either acutely (single dose)
      or repeatedly (twice daily for 14 days). The locomotor hyperactivity induced by 7
      OH-DPAT (3 mg/kg sc) was measured in photoresistor actometers. The influence of
      nafadotride (0.2 and 0.4 mg/kg ip), a dopamine D3-preferring antagonist or
      sulpiride (10 and 25 mg/kg ip), a dopamine D2/D3 antagonist, on the 7-OH-DPAT
      induced locomotor hyperactivity was studied. Nafadotride (in both doses used) or
      sulpiride (in the higher dose only) reduced (by about 50%) the hyperactivity
      induced by 7-OH-DPAT. Combined treatment with nafadotride (0.2 mg/kg) and
      sulpiride (25 mg/kg) completely abolished the effect of 7-OH-DPAT. IMI
      administered repeatedly (but not acutely) enhanced the 7-OH-DPAT-induced
      hyperactivity. Neither nafadotride, 0.2 mg/kg (or sulpiride, 10 mg/kg), given
      alone nor combined treatment with both these substances changed the hyperactivity
      induced by repeated treatment with IMI and 7-OH-DPAT (given 2 h after the last
      dose of IMI). Joint treatment with nafadotride, 0.2 mg/kg, and sulpiride, 25
      mg/kg, completely abolished the enhancing effect of repeated treatment with IMI
      and 7-OH-DPAT. The above results indicate that both types of dopamine receptors,
      D3 and D2, may play a substantial role in the mechanism of the 7-OH-DPAT-induced
      hyperactivity, as well as in the increase evoked by repeated treatment with IMI
      in rats.

PMID- 11985331
TI  - Does combined treatment with novel antidepressants and a dopamine D3 receptor
      agonist reproduce cocaine discrimination in rats?
AB  - It is established that dopamine (DA) neurotransmission plays a critical role in
      the behavioral (e.g. discriminative stimulus) effects of cocaine in rodents.
      Nonetheless, research has also demonstrated that reciprocal signaling between DA
      and monoamine neurotransmitters, i.e. serotonin (5-HT) and norepinephrine (NE)
      has important implication for understanding the actions of cocaine. The present
      study was focussed on the ability of novel antidepressant drugs (milnacipram,
      reboxetine and venlafaxine), which affect either NE or both 5-HT and NE reuptake
      mechanism, to alter (enhance or antagonize) the discriminative stimulus effects
      of cocaine. Moreover, we investigated if the combined treatment with those drugs
      and a DA D3 receptor agonist (pramipexole) could reproduce cocaine
      discrimination. Male Wistar rats were trained to discriminate cocaine (10 mg/kg,
      ip) from saline (ip) in a two-choice, water-reinforced fixed-ratio 20 drug
      discrimination paradigm. Given alone, none of antidepressant drugs induced
      substitution for the cocaine-lever responses. Pramipexole (0.25 mg/kg) produced a
      partial substitution for cocaine (i.e. 43-52% cocaine-lever responding). In
      combination experiments, milnacipram (10 mg/kg) or reboxetine (10 mg/kg) given
      with submaximal doses of cocaine (1.25-5 mg/kg) did not affect the cocaine dose
      response curve or its ED50 values. Venlafaxine (10 mg/kg) given in combination
      with submaximal doses of cocaine (0.6-5 mg/kg) produced significant enhancement
      of cocaine discrimination with a leftward shift in the cocaine dose-response
      curve and a decrease in its ED50 value. Pretreatment with either milnacipram (10
      mg/kg) or reboxetine (10 mg/kg) failed to modulate the partial substitution
      evoked by pramipexole (0.25 mg/kg). On the other hand, venlafaxine (10 mg/kg)
      given in combination with a submaximal dose of pramipexole (0.25 mg/kg), which
      separately elicited 16 and 42% the cocaine-lever responses, produced significant
      enhancement of cocaine discrimination (up to 99% of the drug-lever responding).
      These results indicate that the discriminative stimulus effects of cocaine in
      rats can be enhanced by venlafaxine or mimicked by the combination with this
      antidepressant drug and the DA D3 receptor agonist. This finding, together with
      the recent data reporting the lack of rewarding properties of venlafaxine and the
      attenuation of morphine dependence and withdrwal signs in rats by the drug, may
      indicate a possible therapeutic use of this antidepressant in cocaine abuse.

PMID- 11985332
TI  - Effect of NOS inhibitor on forced swim test and neurotransmitters turnover in the
      mouse brain.
AB  - The previous experiments have demonstrated that NMDA receptor antagonists and
      nitric oxide synthase (NOS) inhibitors have antidepressant- and anxiolytic-like
      activities in rodents. Moreover, chronic treatments with these agents result in
      down-regulation of beta-adrenoceptors in the brain cortex with a magnitude
      comparable to clinically effective antidepressants. However, still little is
      known about the effect of NOS inhibitors on the regulation of neurotransmitter
      utilization in vivo. The aim of present study was to elucidate the effect of NOS
      inhibitor at doses active in forced swim test (FST) on dopamine and serotonin
      turnover in the mouse brain structures. Mice were treated with imipramine (15
      mg/kg ip), electroconvulsive shock (ECS) and NOS inhibitor, N(G)-nitro-L-arginine
      (L-NA) acutely (at doses of 1, 3, 10 mg/kg ip) and chronically (0.3, 1, 3 mg/kg
      ip). Experiments were carried out 1 h after single and 3 h after chronic (21
      days) administration. Metabolism of dopamine and serotonin was investigated using
      high pressure liquid chromatography (HPLC) with electrochemical detection. The
      metabolism rate was calculated as a ratio of a metabolite to the parent amine.
      FST was performed using protocol described previously by Porsolt et al. Now we
      report that L-NA decreases the level of immobility with potency similar to
      imipramine. The effect of L-NA was reversed by NOS substrate, L-arginine. L-NA
      given acutely at doses active in FST did not change the dopamine metabolism rate
      but it did decrease the serotonin turnover rate in the frontal cortex in a manner
      similar to imipramine. Thus, it appears that under basal conditions endogenous NO
      may influence the serotonin turnover, and the acute inhibition of NOS can mimic
      the effect of imipramine what may result in the antidepressant-like effect in
      FST. Imipramine given acutely produced massive increase in the level of serotonin
      in the frontal cortex as well as in the hypothalamus (by 40%, p < 0.01) what was
      reflected in significant decreases in the metabolism rate. Contrary to acute
      effect, chronic treatment of L-NA (the most effective dose was 1 mg/kg) produced
      increase in the dopamine metabolism rate within all investigated structures. In
      the present study, we demonstrated for the first time that L-NA may alter the
      neurotransmitter utilization in vivo and the observed effect may be due to
      adaptational changes in neuronal function.

PMID- 11985333
TI  - N(G)-nitro-L-arginine and its methyl ester inhibit brain synthesis of kynurenic
      acid possibly via nitric oxide-independent mechanism.
AB  - The effect of nitric oxide synthase (NOS) inhibitors on the brain production of
      endogenous glutamate receptor antagonist, kynurenic acid, was estimated in vitro.
      Under standard incubation conditions N(G)-nitro-L-arginine, but not N(G)-nitro-L
      arginine methyl ester, up to 5 mM, or 7-nitroindazole, up to 100 microM,
      inhibited de novo synthesis of kynurenic acid in cortical slices. However, during
      prolonged incubation, N(G)-nitro-L-arginine methyl ester also reduced the
      production of kynurenic acid. The substrate for NOS, L-arginine (up to 5 mM), did
      not influence kynurenic acid synthesis and did not reverse the N(G)-nitro-L
      arginine-evoked changes, suggesting that the observed effects are not related to
      disturbed generation of NO. Enzymatic studies revealed that N(G)-nitro-L-arginine
      and its methyl ester blocked the activity of brain kynurenine aminotransferase
      (KAT) I. The activity of KAT II was diminished only by N(G)-nitro-L-arginine.
      Kinetic analyses have shown that N(G)-nitro-L-arginine and its methyl ester
      reduce Vmax and increase Km of KAT I, whereas N(G)-nitro-L-arginine diminishes
      Vmax of KAT II. In conclusion, we report that N(G)-nitro-L-arginine and its
      methyl ester impair brain synthesis of kynurenic acid, probably via NO
      independent mechanism, what could contribute, at least partially, to the
      enhancement of neurotoxicity or seizures observed in some experimental designs
      based on their use.

PMID- 11985334
TI  - Pharmacometric analysis of alpha1-adrenoceptor function in rat tail artery
      pretreated with lipopolysaccharides.
AB  - The inhibitory effect of lipopolysaccharides (LPS) on contraction evoked by alpha
      adrenergic stimulation is quite well-known, but molecular mechanism of this
      inhibition is unclear. In the present study, an interaction between alpha
      adrenoceptor response and LPS in rat tail artery was investigated using chemical
      stimulation. In the presence of LPS noradrenaline and phenylephrine,
      concentration-response curves were shifted to the right with a change in maximal
      responses. The K(A) and K(B) values calculated in the presence and absence of LPS
      did not differ significantly. The results strongly suggest that LPS did not
      change the affinity of alpha-adrenoceptors. Changes in the plot showing
      relationship between agonist-evoked responses and receptor occupancy in the
      presence of LPS and reduction of K(A)/ED50 value suggest reduction of alpha
      adrenoceptor reserve. In the experiments performed on arteries without
      endothelium, the inhibitory effect of LPS was still present. In the presence of
      atropine, antazoline and indomethacin, the reduction of alpha-adrenoceptor
      reserve was noted, but in the presence of N-omega-nitro-L-arginine methyl ester
      (L-NAME), the inhibitory effect of LPS was not significant. Moreover, in LPS
      pretreated arteries, in the presence of L-NAME, the increase in the receptor
      reserve was observed. It suggests that inhibitory effect of LPS is partially
      reversible. The results strongly indicate that in early endotoxemia, main
      inhibitory effect of LPS is connected with releasing nitric oxide and decreasing
      coupling between alpha1-adrenoceptor and signal induction.

PMID- 11985335
TI  - Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and
      hydroxylation in the rat liver.
AB  - The primary metabolic pathways of caffeine are 3-N-demethylation to paraxanthine
      (CYP1A2), 1-N-demethylation to theobromine and 7-N-demethylation to theophylline
      (CYP1A2 and other enzymes), and 8-hydroxylation to 1,3,7-trimethyluric acid
      (CYP3A). The aim of the present study was to investigate the influence of
      phenothiazine neuroleptics (chlorpromazine, levomepromazine, thioridazine,
      perazine) on cytochrome P-450 activity measured by caffeine oxidation in rat
      liver microsomes. The obtained results showed that all the investigated
      neuroleptics competitively inhibited caffeine oxidation in the rat liver, though
      their potency to inhibit particular metabolic pathways was not equal.
      Levomepromazine exerted the most potent inhibitory effect on caffeine oxidation
      pathways, the effect on 8-hydroxylation being the most pronounced. This indicates
      inhibition of CYP 1 A2 (inhibition of 3-N- and 1-N-demethylation; Ki = 36 and 32
      microM, respectively), CYP3A2 (inhibition of 8-hydroxylations; Ki = 20 microM),
      and possibly other CYP isoenzymes (inhibition of 7-N-demethylation; Ki = 58
      microM) by the neuroleptics. The potency of inhibition of caffeine oxidation by
      perazine was similar to levomepromazine. Thioridazine was a weaker inhibitor of
      caffeine 3-N- and 7-N-demethylation, while chlorpromazine was weaker in
      inhibiting caffeine 1-N- and 7-N-demethylation, compared to levomepromazine. In
      summary, the obtained results showed that all the investigated neuroleptics had a
      broad spectra of CYP inhibition in the rat liver. The isoenzymes CYP1A2 and
      CYP3A2 were distinctly inhibited by all the investigated neuroleptics, while
      other CYP isoenzymes (CYP2B and/or 2E1) by perazine and levomepromazine. The
      CYP3A2 inhibition was most pronounced. (Ki = 20-40 microM).

PMID- 11985336
TI  - In vitro-in vivo correlation of the pharmacokinetics of vinpocetine.
AB  - Vinpocetine is extensively metabolized in rats, dogs and humans, and the plasma
      clearance approximates the hepatic plasma flow in each of the species. In vitro
      degradation studies with hepatocytes have shown that the activity of human
      hepatocytes is about one order of magnitude higher than the activity of dog
      hepatocytes, and two orders of magnitude higher than that of rat hepatocytes.
      These differences can explain the differences in bioavailabilities of vinpocetine
      in the three species (52% in rats, 21.5+/-19.3% in dogs and 6.2+/-1.9% in
      humans). In dogs and humans, the compound seems to be metabolized exclusively in
      the liver whereas in rats extrahepatic metabolism seems also to be important. The
      in vivo clearance predicted from the activity of hepatocytes is in good agreement
      with the values measured in vivo in the case of humans and dogs. The estimated
      values for bioavailability showed good correlation with in vivo data in each
      species if the free drug ratio was assumed to equal 1.

PMID- 11985337
TI  - NADPH-induced oxidative damage of rat liver microsomes: protective role of
      chlorpromazine and trifluoperazine.
AB  - Two widely used antipsychotic drugs, chlorpromazine (CPZ) and trifluoperazine
      (TFZ) inhibit NADPH-induced microsomal lipid peroxidation (LPO). Study of
      microsomal membrane fluidity revealed considerable disorganization in its
      architecture in the presence of NADPH, which can be restored back in the presence
      of CPZ and TFZ. NADPH-dependent microsomal LPO is catalyzed by NADPH: cytochrome
      P450 reductase. These drugs also inhibit the activity of this enzyme. TFZ always
      shows stronger inhibitory effect than CPZ. TFZ contains a trifluromethyl group
      (CF3) in its second position that gives rise to stronger electron abstraction
      tendency by which LPO and NADPH: cytochrome P450 reductase activity is inhibited
      more potently than by CPZ which contains a chlorine ligand in the same position.
      Due to the stronger antioxidant property of TFZ, it can be prescribed as a better
      therapeutic agent, which plays a protective role for the cellular system.

PMID- 11985338
TI  - Repeated imipramine administration enhances the effects of NMDA receptor ligands
      on synchronous activity in rat frontal cortex in vitro.
AB  - This study assessed the effects of repeated administration (14 days) of
      imipramine on the function of NMDA receptors by measuring the frequency of
      spontaneous epileptiform discharges which develop in rat frontal cortical slices
      incubated in Mg2+-free conditions. Imipramine significantly enhanced both the
      excitatory effect of NMDA and the inhibitory effect of the competitive NMDA
      receptor antagonist CGP 37849 on the frequency of discharges. These results are
      consistent with studies indicating that chronic administration of antidepressant
      drugs induces adaptive changes in NMDA receptor/ channel complex in the cerebral
      cortex.

PMID- 11985339
TI  - Rise in zinc affinity for the NMDA receptor evoked by chronic imipramine is
      species-specific.
AB  - Zinc and magnesium are potent inhibitors of the NMDA receptor complex. Previous
      reports demonstrated that both zinc and magnesium, like other NMDA receptor
      antagonists, exhibit antidepressant-like effects in rodent screening tests.
      Moreover, chronic treatment with antidepressants and electroconvulsive shock
      increase zinc concentration in the rat hippocampus. The present study examined
      the effect of tricyclic antidepressant, imipramine, on the potency of zinc and
      magnesium to inhibit [3H]MK-801 binding in the mouse and rat cerebral cortex and
      hippocampus. Chronic treatment with imipramine produced statistically significant
      increase in the potency of zinc to inhibit [3H]MK-801 binding in the mouse
      cerebral cortex but not in the hippocampus. However, this treatment neither
      influenced the zinc affinity in rat tissue nor magnesium affinity in tissue of
      both species. The present data indicate that, although imipramine-induced rise in
      zinc affinity to the NMDA receptor complex is in agreement with previously
      reported antidepressant-induced reduction of the NMDA receptor function, this
      effect is species-specific.

PMID- 11985340
TI  - Aorta response to secretin in intact and diabetic rats.
AB  - The influence of secretin (10(-10) - 10(-8) M), a gastrointestinal hormone, on
      the relaxing response of rat thoracic aorta rings preconstricted by 40 mM KCl was
      studied by measuring changes in isometric tension in intact and diabetic animals.
      Initial contraction of aorta rings was markedly decreased in diabetic state.
      Secretin administered at two higher doses (10(-9), 10(-8) M) caused significant
      relaxation. In diabetes, relaxing effect was observed at all three doses of the
      peptide. These data indicate that secretin relaxes thoracic aorta rings and state
      of diabetes markedly amplifies the relaxant response to this peptide.

PMID- 11985341
TI  - Significance of toxic interactions in medicolegal evidence. Complex fatal
      poisoning with drugs of abuse in the material of the Chair of Forensic Medicine,
      Collegium Medicum, Jagiellonian University in Krakow.
AB  - The subject of the study was fatal complex poisonings with drugs of abuse in two
      young men. In the first case, postmortem investigation revealed cardiotoxic death
      as the result of an interaction between opiates, amphetamine derivatives and
      oxazepam. In the second case, death followed the administration of amphetamine
      derivatives and cocaine (xenobiotics known on the illicit drug market as "UFO").
      Based on the toxicological postmortem analysis the authors discuss the
      interpretation of the results in the light of general problems of interactions
      taking place in toxicokinetic and toxicodynamic phases of intoxication processes.

PMID- 11985342
TI  - Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in the
      rat hippocampus in an animal model of depression.
AB  - The aim of our study was to investigate the level of metabotropic glutamate
      receptors (mGluRs) in the brains of rats after chronic mild stress. Using Western
      blotting procedure we showed that the level of mGluR5 receptor protein was
      increased in CA1 and decreased in CA3 region of the hippocampus. Our results
      indicate that mGluR5 can possibly be engaged in the mechanism of depression.

PMID- 11985343
TI  - Effect of repeated treatment with reboxetine on the central alpha1-adrenergic
      system.
AB  - The obtained results indicate that repeated administration of reboxetine
      (selective noradrenaline reuptake inhibitor, without any affinity for
      neurotransmitter receptors) increased the responsiveness of alpha1-adrenergic
      system (potentiating the methoxamine-induced exploratory hyperactivity in rats
      and clonidine-induced aggressiveness in mice), as tricyclic antidepressants did.
      However, the question whether the increased functional responsiveness found in
      the present study is important for the clinical antidepressant efficacy, remains
      open.

PMID- 11985344
TI  - Opposite effects of olanzapine and haloperidol in rat ultrasonic vocalization
      test.
AB  - The opposite effects of the classical antipsychotic, haloperidol, and atypical
      neuroleptic, olanzapine, in the rat ultrasonic vocalization test of anxiety were
      observed. The present data are discussed in relation to growing body of evidence
      of specific brain biochemical changes after pretreatment with different
      antipsychotics.

PMID- 11985345
TI  - Immunohistochemical evidence for localization of NMDAR1 receptor subunit on
      dopaminergic neurons of the rat substantia nigra, pars compacta.
AB  - Non-fluorescent, double-labeling techniques were used in order to investigate
      whether NMDAR1 receptor subunits are localized on dopaminergic (i.e. tyrosine
      hydroxylase-positive) neurons of the rat substantia nigra, pars compacta. It has
      been found that NMDAR1 receptor subunits are highly abundant in the pars compacta
      neurons and their dendritic processes. It was also found that vast majority, if
      not all, of pars compacta neurons which are positive for the presence of NMDAR1
      receptor subunits are dopaminergic ones. It is concluded that if NMDAR1 receptor
      subunits, an indispensable element of functional NMDA receptor ion channel
      complex, is co-assembled with other subunits of NMDA receptor ion channel
      complex, NMDA receptors might directly control the activity of dopaminergic
      neurons.

PMID- 11985346
TI  - Search for the presence of glucocorticoid receptors in dopaminergic neurons of
      rat ventral tegmental area and substantia nigra.
AB  - Using non-fluorescent immunocytochemical double-labelling procedure and specific
      antibodies visualizing GR (glucocorticoid receptors) and TH (tyrosine
      hydroxylase) we have been looking for the co-localization of both antigens in
      neurons of the rat ventral tegmental area and adjacent substantia nigra. This
      experimental direction has been inspired by the available data showing that
      alterations in the level of circulating glucocorticosteroids have distinct
      effects on the intensity of dopaminergic neurotransmission. Thus, it was of
      interest to find the anatomical background for the above interaction. It has been
      found that the rat ventral tegmental area and substantia nigra possess a
      relatively moderate number of cells with active GR, i.e. receptors which are
      condensed in the nuclei. Further, we found that dopaminergic neurons (TH
      positive) of the ventral tegmental area and substantia nigra were not
      immunopositive for GR. This observation was in the sharp contrast to the results
      from the locus coeruleus, where the co-localization of GR with TH was a general
      rule. Above anatomical data indicate that glucocorticoid receptors influence the
      dopaminergic neurotransmission by an indirect mechanism, which possibly involves
      intermittent neurotransmitter.

PMID- 11985347
TI  - Conditions of application of repeated transcranial magnetic stimulation to rats
      may mask the effects of the treatment.
AB  - Rats of sham repeated transcranial magnetic stimulation (rTMS) group, kept in
      noisy room and transiently immobilized (5 min) for 12 consecutive days, showed
      similar inhibition of body weight gain, increase in exploratory locomotor
      activity, and elevation of motor response to apomorphine as rats undergoing
      magnetic stimulation of the brain, and had only slightly lower response in
      apomorphine stereotypy. Some of the responses ascribed to antidepressant action
      of rTMS in animal experiment may be due to environmental conditions, and not
      alternating magnetic field passing the brain.

PMID- 11985348
TI  - Influence of new gamma-aminobutyric acid amide derivatives and its phthalimide
      precursors on the central nervous system activity in mice.
AB  - The present study investigated the influence of BM-78, BM-121 (gamma-aminobutyric
      acid amide derivatives) and BM-42, BM-43 (phthalimide precursors of BM-78 and BM
      121) on the spontaneous locomotor activity and on the picrotoxin-induced
      seizures. Results of pharmacological in vivo examination of the effects of new
      gamma-aminobutyric acid amide derivatives and its phthalimide precursors
      (compounds BM-78, BM-121, BM-42, BM-43), presented in this paper showed that all
      the compounds had different but clear influence on CNS in mice.

PMID- 11985349
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) activate protein kinase C in chick cerebral cortex.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP38) and vasoactive
      intestinal peptide (VIP) were tested for their ability to influence protein
      kinase C (PKC) activity in the chick cerebral cortical slices. Thirty minutes
      incubation of the chick tissue with PACAP38 (0.1-1 microM) or VIP (0.3-3 microM)
      produced significant and concentration-dependent changes in PKC activity. Both
      peptides enhanced the enzyme activity in cell membrane preparation, and decreased
      it in cytosol preparation obtained from cerebral cortical slices. These changes
      in PKC activity suggest that PACAP and VIP are capable of activating this enzyme
      in cerebral cortex of chick.

PMID- 11985350
TI  - Betahistine inhibits food intake in rats.
AB  - Betahistine, administered intraperitoneally, decreased, in a dose-dependent
      manner and in a statistically significant degree, total food intake in different
      experimental models in rats.

PMID- 11985351
TI  - Influence of thalidomide on Bcl2 expression and proangiogenic cytokine levels in
      short-term culture of peripheral blood and bone marrow mononuclear cells of
      multiple myeloma patients.
AB  - Supernatants from short-term culture of peripheral blood and bone marrow
      mononuclear cells obtained from 22 multiple myeloma patients were used to measure
      the concentration of TNF-alpha, HGF, IL-6 and its soluble receptor (sIL-6R), VEGF
      and bFGF. Cells were cultured with or without thalidomide (THAL). We observed
      statistically significant decrease in TNF-alpha, HGF, IL-6, sIL-6R in
      supernatants from THAL cultures compared to cells cultured without THAL. Flow
      cytometry technique was applied to study the Bcl2 expression on CD 4, CD 8 and CD
      138 positive cells. The statistically significant decrease in Bcl2 expression on
      myeloma cells (CD 138+) was observed both in PB and BM cultures. THAL could
      inhibit the plasma cell growth both by diminishing proangiogenic cytokines
      production and enhancing myeloma cell apoptosis.

PMID- 11985352
TI  - Expression of proenkephalin (PENK) mRNA in inflammatory leukocytes during
      experimental peritonitis in Swiss mice.
AB  - Zymosan- or thioglycollate-induced experimental peritoneal inflammation in mice
      may serve as a convenient model for investigations of involvement of opioid
      peptides derived from exudatory leukocytes in the inflammatory processes. During
      peritonitis, the influx of neutrophils and monocytes/macrophages correlated with
      a sequential appearance of proinflammatory cytokines (IL-1beta and TNFalpha).
      After both kinds of stimulation, the expression of PENK mRNA was much higher in
      exudatory peritoneal leukocytes than its basal level in steady state.

PMID- 11985353
TI  - Fluorescence of yellow budgerigars.

PMID- 11985354
TI  - Another look at MgB2 and YBCO wires.

PMID- 11985355
TI  - Cryopreservation: freezing and vitrification.

PMID- 11985356
TI  - Antiaging technology and pseudoscience.

PMID- 11985357
TI  - URRs and Nobel Prizes.

PMID- 11985358
TI  - Nasal reconstruction in ancient India.

PMID- 11985359
TI  - Family health nurse pilot project.

PMID- 11985360
TI  - Problems associated with foot supports.

PMID- 11985362
TI  - In the matter of anonymous, a minor: fetal representation in hearings to waive
      parental consent for abortion.

PMID- 11985363
TI  - Antitrust, health care quality, and the courts.
AB  - Antitrust law represents the principal legal tool that the United States employs
      to police private markets, yet it often relegates quality and nonprice
      considerations to a secondary position. While antitrust law espouses the belief
      that vigorous competition will enhance quality as well as price, little evidence
      exists of the practical ability of courts to deliver on that promise. In this
      Article, Professors Hammer and Sage examine American health care as a vehicle for
      advancing understanding of the nexus among competition, quality, and antitrust
      law. The Article reports results of a comprehensive empirical review of judicial
      opinions in health care antitrust litigation between 1985 and 1999, with specific
      attention to courts' handling of quality and other nonprice concerns. Professors
      Hammer and Sage conclude that, although antitrust law cannot be expected to serve
      as the sole oversight mechanism for industries as complex and quality dependent
      as health care, courts have been successful incorporating some nonprice factors
      into antitrust analysis.

PMID- 11985364
TI  - Computer-enhanced surgical systems ("robotic surgery").
AB  - Computer-linked surgical systems allow surgeons to perform procedures without
      coming into contact with the patient. Indications for these robotic surgery
      systems are expanding. This technology offers potential advantages through
      enabling more precise surgery, which may lead to shorter patient recovery times,
      fewer complications and improved patient outcomes. Limited studies indicate the
      promise of these systems, which appear to be safe, but their efficacy is not
      fully established. In some procedures, the advantages they offer may also be
      achieved by newer non-computer assisted techniques. Capital costs are high and
      cost-effectiveness has not been demonstrated. Diffusion of these systems can be
      expected to continue, but their place in surgical practice is not yet clear. They
      are most likely to be of value for centres undertaking specialized surgical
      services.

PMID- 11985365
TI  - Activated protein C for severe sepsis.
AB  - Severe sepsis is a systemic inflammatory response to infection involving organ
      dysfunction. Severe sepsis is a common cause of death and is associated with a
      20% to 56% mortality rate. Drotrecogin alpha (activated) is a recombinant human
      activated protein C(rhAPC) approved in the U.S. for the reduction of mortality in
      adult patients with severe sepsis who have a high risk of death. Drotrecogin
      alpha (activated), when administered to adult patients with clinically defined
      severe sepsis, demonstrated a 6.1% absolute reduction (p=0.005) in 28-day all
      cause mortality in one published, randomized, double-blind study of 1,690
      patients (PROWESS). Drotrecogin alpha (activated) is used as an adjunct to
      standard therapy and is therefore and "add-on" cost. Close attention must be paid
      to proper patient selection for treatment with drotrecogin alpha (activated).
      Certain individuals, such as those at a greater risk of bleeding, could be harmed
      from therapy. The benefit or harm in individuals not meeting the trial selection
      criteria is uncertain.

PMID- 11985366
TI  - Clozapine: new preparation. A last resort for parkinsonian patients with
      psychosis.
AB  - (1) Psychotic disorders occurring in patients with Parkinson's disease are
      usually linked to antiparkinsonian treatments. Tapering the dose of dopaminergic
      or anticholinergic drugs does not always yield a satisfactory balance between the
      psychotic and motor disorders. Most neuroleptics tend to worsen extrapyramidal
      manifestations and are contraindicated in combination with dopaminergic agents.
      Their assessment in patients with Parkinson's disease has been limited. (2)
      Clozapine, a neuroleptic, is now indicated in this type of patient. (3) The
      evidence comes from two double-blind placebo-controlled trials, each involving 60
      patients. In these trials, 40% of patients lost all their psychotic disorders on
      low-dose clozapine, usually with no worsening of parkinsonian manifestations. (4)
      In clinical trials of clozapine in Parkinson's disease, the incidence of
      neutropenia was between 2 and 3%, and that of agranulocytosis 0.3%. The risks of
      myocarditis, dilated myocardiopathy and malignant neuroleptic syndrome associated
      with clozapine call for strict pharmacovigilance. (5) In practice, when adjusting
      antiparkinsonian treatment fails to strike a balance between psychotic and
      parkinsonism disorders, clozapine is the standard neuroleptic. It should be used
      with care, however, because of its adverse effects.

PMID- 11985367
TI  - Orlistat: a second look. At best, a minor adjunct to dietary measures.
AB  - (1) Treatments for obesity are disappointing, and none has yet shown an effect on
      morbidity or mortality. Non drug treatments have not been assessed adequately.
      Long-term maintenance of weight loss requires long-term patient management. (2)
      Orlistat, a gastrointestinal lipase inhibitor, is licensed in Europe for the
      treatment of obesity, in combination with a low-calorie diet. (3) The risk
      benefit ratio of orlistat could not be estimated from the initial assessment file
      in 1999. There were fears over a possible increase in the risk of breast cancer.
      (4) Few new efficacy data have been obtained since. Medium-term trials (12-24
      months) show that orlistat (120 mg three times a day), combined with dietary
      intervention, has a minor supplementary effect on weight loss (-3.5 kg on
      average). (5) A meta-analysis of three of the four available comparative trials
      lasting two years failed to conclude that orlistat prevents the onset of type 2
      diabetes. Likewise, there is no firm evidence that orlistat lowers cardiovascular
      morbidity or mortality. (6) Orlistat frequently has gastrointestinal adverse
      effects, and case reports of hypertension have been published. Orlistat probably
      interacts with a number of other drugs. (7) Follow-up of nearly 8,000 women for
      only a few years showed no increase in the incidence of breast cancer on
      orlistat. (8) In practice, dietary intervention and risk factor management remain
      the cornerstones in the management of obesity. Orlistat is only a minor, optional
      and temporary aid, although it appears so far to have no serious adverse effects.

PMID- 11985368
TI  - Tinzaparin: new indication. Easier treatment of less severe pulmonary embolism.
AB  - (1) The standard first-line antithrombotic treatment for pulmonary embolism in
      patients without cardiovascular shock or marked hypotension is intravenous
      infusion of unfractionated heparin for a few days, followed by several months of
      oral anticoagulation. (2) In France, tinzaparin is the first low-molecular-weight
      heparin (LMWH) to be licensed specifically for treating pulmonary embolism (one
      subcutaneous injection daily). (3) The clinical file mainly comprises data from a
      comparative unblinded trial versus unfractionated heparin in 612 patients, which
      shows tinzaparin to have no advantage in terms of overall mortality or the
      incidence of bleeding. A trial comparing unfractionated heparin with another
      LMWH, reviparin, gave similar results. (4) In practice, tinzaparin offers the
      advantage over unfractionated heparin of not requiring intravenous
      administration. For the least severely ill patients, tinzaparin is an advance.
      Close laboratory monitoring of clotting factors is warranted for elderly and
      obese patients, and those with renal impairment. For other patients, intravenous
      infusion of unfractionated heparin remains the standard treatment for pulmonary
      embolism.

PMID- 11985369
TI  - Drugs can trigger pathological gambling.
AB  - Dopaminergic drugs can trigger pathological gambling in patients with Parkinson's
      disease.

PMID- 11985370
TI  - Severe liver damage on terbinafine.

PMID- 11985371
TI  - Drugs and breast-feeding.
AB  - (1) Report of severe adverse effects in infants from drugs passing into breast
      milk are rare. (2) Two reports of neurological disorders in infants due to
      doxepin, a tricyclic antidepressant, necessitating hospitalisation, serve as a
      reminder that this risk exists. (3) Epidemiological data are almost non existent.
      A prospective follow-up study of more than 800 breast-fed infants whose mothers
      were taking medicinal drugs showed minor adverse effects in 11% of the children
      (mainly diarrhoea, drowsiness and irritability). None of the mothers sought
      medical advice. (4) When a breast-feeding mother requires drug therapy, all
      available information should be weighed up before advising her to switch to
      bottle feeding.

PMID- 11985372
TI  - Simple febrile convulsions in children: explain and reassure the parents.
AB  - (1) Simple febrile convulsions (brief and generalised) in children carry a high
      risk of recurrence during new febrile episodes (30-50%), especially while the
      child is under the age of 3 years. These relapses are rarely severe and only
      occur during a minority of febrile episodes. Later onset of epilepsy is rare. (2)
      Long term treatment with phenobarbital and valproic acid reduce the risk of
      relapse but carry a risk of bothersome or severe adverse effects. These
      treatments are rarely warranted in this setting. (3) Oral diazepam administration
      to a febrile child has moderate preventive efficacy, which is further limited by
      the difficulty of timing the treatment correctly. Oral diazepam has frequent but
      generally mild adverse effects. (4) Antipyretics are not very effective at
      preventing febrile convulsions but can make the child more comfortable. (5)
      Parents are often upset when they first see their child have a febrile
      convulsion. It is important to take the time to reassure them.

PMID- 11985373
TI  - Highlights of the 22nd French pharmacovigilance meeting.
AB  - (1) The 22nd French pharmacovigilance meeting, held in July 2001, presented data
      on adverse effects notified by health professionals to regional pharmacovigilance
      centres in France. (2) Non specific "immunostimulants" are not harmless placebos,
      as might be concluded from the relative lack of data. There have been 315
      notifications of severe adverse effects, some with positive rechallenge,
      reporting cutaneous, gastrointestinal, respiratory, haematological and other
      disorders. Attributability was considered "likely" in 68% of cases. Three deaths
      occurred. (3) Other well known adverse effects continue to occur: convulsions
      with camphor, visual hallucinations with oxybutynin, headache with antimigraine
      drugs, liver damage with dextropropoxyphene, neuropsychological disorders after
      buflomedil overdose (especially in patients with renal failure), hyperkalaemia
      during spironolactone combination with an angiotensin-converting-enzyme inhibitor
      (ACE inhibitor), and severe infections after intravesical BCG. (4) Rare adverse
      effects of old drugs were identified, such as oedema with valproic acid,
      interstitial pneumonia with flecainide, and a bleeding risk due to tramadol
      interaction with oral anticoagulants. (5) The adverse effects of new drugs are
      better documented: celecoxib is now implicated in visual disorders. (6) Overall,
      the meeting confirmed that only a small proportion of adverse drug reactions are
      notified, that a large number of hospitalised patients suffer from drug induced
      complications, and that summaries of product characteristics (SPC) are often too
      brief or reassuring regarding pharmacovigilance data. The poor risk-benefit
      ratios of some drugs call for their immediate market withdrawal.

PMID- 11985374
TI  - Management of advanced-stage ovarian cancer: median survival rate about 2-3
      years.
AB  - (1) Most cases of ovarian cancer are diagnosed at an advanced stage (peritoneal
      extension beyond the pelvis or distant metastases). (2) The standard treatment is
      surgery followed by chemotherapy with paclitaxel + platinum salt. Data favouring
      carboplatin over cisplatin in this setting are of poor quality. (3) There is no
      standard second-line chemotherapy regimen.

PMID- 11985375
TI  - Drug packaging: safety and convenience above all.

PMID- 11985376
TI  - 7-valent pneumococcal conjugate vaccine: new preparation. Prevents rare invasive
      infections in infants.
AB  - (1) Infants under two years of age are the children most exposed to invasive
      pneumococcal infections (meningitis and bacteraemia). The estimated incidence in
      France is about 45 cases per year per 100,000 in the first year of life. The 23
      valent pneumococcal polysaccharide vaccine is ineffective in children under two
      years of age. (2) Marketing authorization has now been granted for a 7-valent
      pneumococcal conjugate vaccine for children under two years. It is the first
      pneumococcal vaccine specifically designed for this age group. (3) Its
      immunogenicity in 2 year old children has been carefully documented. (4) A
      comparative, randomised, double-blind trial involving nearly 38,000 Californian
      infants showed a lower incidence of both all invasive pneumococcal infections
      (approximately 1 case avoided per 400 children vaccinated), and those due to the
      7 serotypes covered by the vaccine. (5) These results are not directly applicable
      to France, where the pneumococcal serotype distribution (especially the 7
      serotypes covered by the vaccine) seems to be somewhat different, and where the
      incidence of invasive pneumococcal infections is much lower. (6) The 7-valent
      vaccine has not been assessed adequately in children who are at high risk for
      invasive pneumococcal infection. Some small studies of children with sickle-cell
      disease show adequate immunogenicity. (7) The known adverse effects of the 7
      valent vaccine are acceptable, mainly comprising local reactions and fever. (8)
      The risk of an epidemiological shift towards serotypes not covered by the vaccine
      (through pharyngeal carriage and invasive infection) cannot been ruled out. In
      otitis media, an increase in pneumococcal infections due to serotypes not covered
      by the vaccine negates the benefit of vaccination. (9) In practice, considering
      the severity of invasive pneumococcal infections and the documented efficacy and
      safety of the 7-valent conjugate vaccine, vaccination is warranted for individual
      children under two years of age, especially those at risk, but epidemiological
      monitoring and pharmacovigilance must continue.

PMID- 11985377
TI  - Lumbar puncture and the risk of herniation: when should we first perform CT?
AB  - Death following lumbar puncture (LP) is feared by physicians. Many opinions are
      found in literature on the question whether computed cranial tomography (CT)
      should be performed before LP, to prevent herniation. These opinions are mainly
      based on retrospective studies and pathophysiological reasoning. In this review
      the difficulties in the decision whether we should perform CT before LP are
      discussed. It is explained that the concept of "raised intracranial pressure" is
      confusing, and that the less ambiguous terms "brain shift" and "raised CSF
      pressure" should be used instead. Brain shift is a contraindication to LP,
      whether CSF pressure is raised or not, and whether papilloedema is present or
      not. Subsequently, recommendations are offered for indications to perform CT
      before LP, grouped according to the safety and clinical utility of LP.

PMID- 11985378
TI  - The heterogeneity of idiopathic Parkinson's disease.
AB  - The diagnosis of Idiopathic Parkinson's disease (IPD) requires post mortem
      neuropathological confirmation to be secure, since there is marked heterogeneity
      in the clinical phenotype of these patients. Pathologically confirmed IPD
      encompasses a spectrum of microscopic appearances with respect to the extent and
      distribution of Lewy Body deposition, which may reflect the clinical phenotypes
      observed during life. In this review, we discuss how IPD is currently defined and
      the purpose and applications of a classification of the disease. We have also
      performed a systematic review of the literature to present the quantitative
      evidence on which potential classifications of the disease might be based. This
      evidence suggests that sub-groups based on age of onset, motor presentation, or
      subsequent motor phenotype may have some use in predicting disease progression.
      However, further clinicopathological studies are required to evaluate
      pathological heterogeneity within these groups. Clinical sub-groups may be
      related to a variety of as yet unknown risks, including genetic factors for both
      the familial and sporadic forms of the disease, and may have far reaching
      consequences for our understanding of disease pathogenesis and treatment
      strategies.

PMID- 11985379
TI  - Endocrine rhythms in patients with restless legs syndrome.
AB  - There is increased evidence that the dopaminergic system plays a major role in
      the pathophysiology of the restless legs syndrome (RLS). Dopamine is the major
      inhibitory factor of prolactin release and also influences growth hormone (hGH)
      secretion. The aim of this study was to measure the endocrine activity of RLS
      patients, to compare it with that of normal subjects and to detect possibly
      altered patterns of hormonal secretion in RLS patients. Prolactin, hGH and
      cortisol plasma levels were measured every 20 min for 24 hours in 10 male never
      medicated RLS patients (aged 56 +/- 6 years) who have had mild to moderate
      symptoms for 15 +/- 10 years and in 8 age-matched male controls (aged 57 +/- 5
      years). The blood samples taken during the night were paralleled by
      polysomnographic recordings including the assessment of periodic leg movements
      (PLM). Plasma levels as well as frequency and amplitude of the pulses of
      prolactin, hGH and cortisol were not different between RLS patients and controls.
      Both groups showed the same rhythms during the night- and daytime for all
      hormones. Cross correlations resulted in high correlation coefficients for each
      hormone at lag 0 (0.964,0.943 and 0.971 for mean locations of cortisol, hGH and
      prolactin, respectively). Concerning sleep parameters, there were no significant
      differences between the two groups apart from a higher PLMS arousal index in RLS
      patients (25.9 +/- 17.1) compared with the controls (12.0 +/- 9.2; p < 0.05). It
      is suggested that a possible dysfunction of the dopaminergic system in RLS does
      not affect the release of prolactin and hGH from the pituitary gland.

PMID- 11985380
TI  - The costs of multiple sclerosis: a cross-sectional, multicenter cost-of-illness
      study in Italy.
AB  - OBJECTIVES: To estimate the socio-economic impact of multiple sclerosis (MS) in
      Italy. METHODS: Outpatients with MS were enrolled at 44 centres across Italy.
      Socio-demographic, clinical and resource utilization data were collected using a
      validated questionnaire. Each patient completed a weekly diary of expenses due to
      MS over a three-month period. Direct health care costs and indirect costs (lack
      of productivity for the patient and for caregivers) were assessed for the whole
      population and were compared among five groups, categorised by disease severity
      (EDSS score). An analysis of variance was carried out on socio-demographic
      variables. RESULTS: For the total population of 566 patients, the mean direct
      cost over three months was ITL 2,134,000, the mean indirect cost was ITL
      7,775,000. Costs were significantly higher for male patients (p < 0.05) and
      showed a significant increase with increasing age (p < 0.0005), disease duration
      (p < 0.0005) and disease severity (p < 0.0005). Costs for patients in a
      progressive phase were significantly higher (p < 0.0005). There were no
      significant geographical differences among the regions of Italy. CONCLUSIONS:
      This study confirms that MS represents a high economic burden, with indirect
      costs greatly exceeding direct costs. Unpaid caregivers remain the culturally
      accepted mode of care for MS patients in Italy and this study illustrates the
      impact of their loss of earnings. As costs increase with disease progression,
      these findings suggest that treatment efforts should focus on patients in the
      early stages of MS, in order to slow down disease progression.

PMID- 11985381
TI  - SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless
      legs syndrome with periodic leg movements in sleep.
AB  - Restless legs syndrome (RLS) is a common sleep-related disorder principally
      characterised by leg paresthesia associated with an irresistible urge to move. A
      majority of RLS patients experience periodic leg movements during sleep (PLMS)
      and wakefulness. Pharmacological evidence suggests that RLS-PLMS may be caused by
      a central nervous system dopaminergic (DA) dysfunction. The aim of the present
      study was to evaluate the striatal pre- and postsynaptic DA status in patients
      suffering from both RLS and PLMS, by means of [123I] beta-CIT and [123I]IBZM
      SPECT respectively. Ten drug-naive patients and ten age-matched controls
      participated in this study. All participants were recorded for at least one night
      of polysomnography before the SPECT studies. No difference was seen in DA
      transporter ([123I] beta-CIT) binding between RLS-PLMS patients (MD=4.89) and
      controls (MD=4.81; p=0.81). The study of the striatal D2-receptor binding
      ([123I]IBZM) revealed a significantly lower binding in patients (MD= 1.72)
      compared with controls (MD=1.85; p=0.006). These results support the hypothesis
      that a central DA dysfunction is involved in the physiopathology of RLS-PLMS.
      Several mechanisms may be responsible for the decrease of the D2-receptor
      binding. However, since [123I] beta-CIT binding is normal, a decreased number of
      D2-receptors or a decreased affinity of D2-receptors for [123I]IBZM is more
      likely than an increased level of synaptic DA with attendant downregulation of D2
      receptors.

PMID- 11985382
TI  - Monitoring disease activity and progression in primary progressive multiple
      sclerosis using MRI: sub-voxel registration to identify lesion changes and to
      detect cerebral atrophy.
AB  - OBJECTIVE: To explore the potential usefulness of two new magnetic resonance
      imaging (MRI) analysis techniques for assessment of progressive cerebral atrophy
      and T2 lesion activity in primary progressive multiple sclerosis (PPMS), and
      thereby assess the relationship between MRI activity and atrophy in this patient
      group. BACKGROUND: Measurements of cerebral atrophy and net change in T2 lesion
      volumes are currently used as surrogate markers of disease progression in
      multiple sclerosis (MS). However, manual implementation of these techniques is
      time-consuming and the pathological specificity of T2 lesion change is low.
      Advances in serial scan registration have facilitated the development of a new,
      fully-automated technique to measure cerebral volume (SIENA; Structural Image
      Evaluation, using Normalisation, of Atrophy), and a technique to measure the
      total new T2 lesion volume selectively (MRI difference imaging). METHOD: SIENA
      measures changes in cerebral size based on sub-voxel detection of shifts in edge
      contours. The lesion difference imaging method measures differences in lesion
      volumes over time as defined by a semi-automated outlining technique. The two new
      methods were validated against the T2 lesion volume contour technique and a
      previously described measure of partial brain volume (which uses six slices
      centred on the presumed area of greatest change around the lateral ventricles).
      All were applied to serially acquired MR images from a cohort of 39 patients with
      PPMS, who also underwent scoring on the expanded disability status scale (EDSS)
      twice, two years apart. RESULTS: The two measures reflecting cerebral atrophy
      correlated strongly (r = 0.58, p < 0.001). T2 lesion load measurements using the
      two techniques correlated very highly (r = 0.999, p < 0.001). 91% of the total
      new T2 lesion volume was from enlargement of pre-existent lesions and only 9 %
      from new, discrete, lesions. No relationship was seen between the traditional
      measure of net gain in T2 lesion load and either measure of atrophy. However, the
      fully-automated measure of total new T2 load correlated with both measures of
      atrophy (SIENA technique, r= -0.37, p= 0.02; six slice measure, r = -0.41, p =
      0.01). There was no relationship between the MRI measures and changes in the
      EDSS. CONCLUSION: Both of the new image analysis techniques appear to be
      promising as sensitive markers for disease progression in PPMS. The correlation
      of total new T2 lesion volume with the progression of cerebral atrophy (which is
      known to be a consequence of axonal loss in progressive disease), compared with a
      lack of correlation with the traditional net gain in T2 lesion load is
      interesting and suggests that the total new T2 lesion volume may ultimately be
      the most useful measure.

PMID- 11985383
TI  - Use of the short form health survey (SF-36) in patients with amyotrophic lateral
      sclerosis: tests of data quality, score reliability, response rate and scaling
      assumptions.
AB  - OBJECTIVES: To evaluate response rate, data quality, score reliability and
      scaling assumptions of the 36 item Short Form Health Survey (SF-36) in a large
      scale pan European survey of amyotrophic lateral sclerosis (ALS) patients.
      DESIGN: A questionnaire based survey of patients diagnosed with ALS across 15
      European countries. SAMPLE PATIENTS: presenting at neurological clinics for
      treatment of their condition were asked to partake in the survey. RESULTS: 948
      patients have been recruited into the survey, from whom responses have been
      gained in 754 (79.5%). Scores on the eight dimensions of the SF-36 were found to
      manifest high internal consistency reliability. Items were, in most instances,
      found to be most highly correlated with their own (corrected) scale score than
      with other scale scores. However, on two dimensions (role-physical and role
      emotional) there was high levels of missing data, together with substantial floor
      and ceiling effects. The two factor model (of underlying constructs of physical
      and emotional health) for the SF-36 suggested by the developers was not supported
      in this patient group. CONCLUSION The SF-36 appears to provide reliable
      information for this patient group, and for the most part there are high levels
      of item completeness and good spread of scores. This is not, however, true for
      the role functioning dimensions. Furthermore, the underlying two factor model for
      the SF-36 was not supported. The implications for measuring health status in this
      patient group are discussed.

PMID- 11985384
TI  - Interferon beta1a (Avonex) treatment in multiple sclerosis: similarity of effect
      on progression of disability in patients with mild and moderate disability.
AB  - OBJECTIVE: To compare clinical responses to once-weekly intramuscular interferon
      beta-1 a [IFNbeta-1 a, Avonex, Biogen] in multiple sclerosis (MS) patients with
      baseline Expanded Disability Status Scale (EDSS) < or = 3.5 or > 3.5. METHODS:
      Patients with relapsing-remitting MS (RRMS), 124 with baseline EDSS < or = 3.5
      and 64 RRMS patients with EDSS > 3.5, were consecutively recruited to receive
      IFNbeta-1 a 30 microg as a once weekly injection for 18 months. The primary
      endpoint of the study was the number of patients in each group with sustained
      worsening in disability, defined as 1-point deterioration in EDSS that persisted
      for at least 6 months during the 18 month follow-up period. Subordinate endpoints
      included relapse rates and the number of treatment dropouts. RESULTS: Among
      patients with baseline EDSS < or = 3.5,16.9% experienced a deterioration in EDSS
      of at least 1 point; 22.5% experienced a deterioration of at least 0.5%.
      Corresponding rates in patients with baseline EDSS > 3.5 were 23.4% and 29%
      respectively (no significant differences between patients stratified according to
      baseline EDSS status). The proportion of patients discontinuing therapy was
      significantly higher in patients with baseline EDSS > 3.5 than in those with
      baseline EDSS < or = 3.5 (16/64 versus 12/124; p = 0.005). At the conclusion of
      follow-up, IFNbeta-1 a therapy was associated with a 31.7% reduction in relapse
      rate in patients with baseline EDSS < or = 3.5 and a 37% reduction in those with
      baseline EDSS > 3.5 (difference not significant). CONCLUSIONS: During 18 months
      of treatment and follow-up, no difference was observed in clinical responses to
      IFNbeta-1 a between RRMS patients with mild and moderate disability but
      discontinuation of therapy was more frequent in the more disabled group.

PMID- 11985385
TI  - Recanalization of acute symptomatic occlusions of the internal carotid artery.
AB  - BACKGROUND: Little is known about the natural course of internal carotid artery
      (ICA) occlusion and its possible recanalization. The present study was designed
      to evaluate recanalization rates of extracranial ICA occlusions in acute stroke
      patients by means of color-coded duplex sonography (CCDS). METHODS: 305 patients
      with acute ischemia in the territory of the middle cerebral artery were included
      in this study. All patients had a neurological examination on admission and on
      discharge and were rated by means of the European Stroke Scale (ESS).
      Extracranial color-coded duplexsonography, transcranial Doppler sonography and
      cranial computed tomography were immediately performed after admission and within
      7 days. RESULTS: 254 patients showed no sign of hemodynamic relevant stenosis
      greater than 70% of the ICA. 21 patients had symptomatic high grade ICA stenosis.
      20 patients had an acute occlusion and 10 patients an old ICA occlusion as judged
      by duplex sonographic criteria. Six patients (5 male, 1 female; age range 57 to
      77 years) with an acute atherothrombotic or cardioembolic occlusion showed a
      recanalization of the ICA in the follow-up ultrasonography. Two patients with
      cardiogenic embolic occlusion of the ICA had the most favorable outcome and these
      patients showed no residual stenosis. 4 patients who had ultrasound findings
      consistent with atherosclerosis on follow-up examination (2 high-grade stenosis,
      2 with carotid plaques) did not show a notable improvement of their ESS-score.
      Patients with carotid plaques developed complete MCA infarctions; the other 4
      patients had partial anterior circulation infarction on follow-up CT.
      CONCLUSIONS: The present study showed that recanalization of the occluded ICA in
      acute stroke patients is more frequent than generally presumed. CCDS should be
      routinely performed in the follow-up of stroke patients as spontaneous
      recanalization may influence clinical outcome.

PMID- 11985386
TI  - The relationship between lesion and normal appearing brain tissue abnormalities
      in early relapsing remitting multiple sclerosis.
AB  - BACKGROUND: In multiple sclerosis (MS), pathological changes have been found both
      in macroscopic lesions and normal appearing tissue. Magnetisation transfer ratio
      (MTR) and T1 relaxation time are abnormal in normal appearing tissues in
      established MS. This study used these MR techniques in early MS to study normal
      appearing tissues and lesions. The purpose was to determine whether abnormalities
      are already detectable in normal appearing tissues in early MS, and if so how
      they correlate with lesion characteristics. METHODS: Twenty two patients with
      early relapsing remitting (RR) MS (median disease duration 2 years, range 7
      months-3 years) and 11 age-matched controls were studied. MTR and T1 relaxation
      times were measured in 9 regions of normal appearing white matter (NAWM) and 7 of
      normal appearing grey matter (NAGM). Gadolinium enhancing, T1-hypointense and T2
      lesion loads were measured in all patients. RESULTS: When all regions were
      combined, there was a significant difference between patient and control NAWM for
      both T1 and MTR; T1 was abnormal in 6/9 and MTR in 3/9 NAWM regions. Global
      assessment of NAGM revealed a significant difference between patients and
      controls for Ti but not for MTR; T1 was significantly abnormal only in frontal
      NAGM. There was no significant correlation between NAWM T1 or MTR and any of the
      lesion load measurements. CONCLUSIONS: This study reveals quantitative MR
      abnormalities in both NAWM and NAGM in early RR MS, with more extensive changes
      in the former. The lack of correlation between NAWM and lesion abnormalities
      suggests that they have developed by at least partly independent mechanisms. T1
      may be more sensitive than MTR in detecting subtle pathological changes in NAWM
      and NAGM.

PMID- 11985387
TI  - Missense and splice site mutations in SPG4 suggest loss-of-function in dominant
      spastic paraplegia.
AB  - We studied nine Italian families with a pure form of autosomal dominant spastic
      paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We
      observed marked intrafamilial variability in both age-at-onset and clinical
      severity, ranging from severe congenital presentation to mild involvement after
      age 55 years to healthy carriers of the mutation after age 70. Four of nine
      probands harboured SPG4 mutations, We identified three new SPG4 mutations, all
      predicting a loss-of-func-tion with apparently important consequences for spastin
      function. RT-PCR studies predict loss-of-function as a possible mechanism leading
      to spastin-related HSP. The current study expands the spectrum of allelic
      variants in SPG4, confirming their pathological significance in pure AD-HSP and
      suggesting implications for the presumed function of spastin.

PMID- 11985388
TI  - Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised
      placebo-controlled trial.
AB  - BACKGROUND: Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are
      allelic disorders with distinct types of mutations in the CACNA1A gene. EA2
      attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase
      inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.
      OBJECTIVES: To evaluate the efficacy and the tolerability of acetazolamide in
      migraine prophylaxis. METHODS: We compared daily oral 500 mg acetazolamide and
      placebo in patients with migraine in a multicentre, double-blind, randomised
      trial of 12 weeks duration after a run-in period of 4 weeks without treatment.
      Frequency of attacks at the last trial period of 4 weeks was the primary efficacy
      criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks,
      the severity and duration of attacks, the number of hours with migraine as well
      as the number of responders with more than 50% reduction in attack frequency.
      RESULTS: 53 patients had been enrolled when the study was prematurely stopped
      because of a high number of withdrawals (34%), primarily linked to acetazolamide
      related side effects. Considering the primary and secondary efficacy criteria,
      among the 53 included patients (27 in the placebo group and 26 in the
      acetazolamide group), no difference between the 2 study groups could be
      demonstrated. The most frequent adverse events related to acetazolamide were
      paresthesias and asthenia. CONCLUSIONS: In this trial, migraine sufferers poorly
      tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious
      prophylactic beneficial effect of acetazolamide appeared on migraine attacks.

PMID- 11985389
TI  - T cell vaccination in multiple sclerosis: results of a preliminary study.
AB  - Myelin basic protein (MBP)-reactive T cells are potentially involved in the
      pathogenesis of multiple sclerosis (MS), and can be depleted by subcutaneous
      inoculations with irradiated autologous MBP-reactive T cells (T cell
      vaccination). This preliminary open label study was undertaken to evaluate
      whether depletion of MBP-reactive T cells would be clinically beneficial to
      patients with MS. Fifty-four patients with relapsing-remitting (RR) MS (n=28) or
      secondary progressive (SP) MS (n=26) were immunized with irradiated autologous
      MBP-reactive T cells and monitored for changes in rate of relapse, expanded
      disability scale score (EDSS) and MRI lesion activity over a period of 24 months.
      Depletion of MBP-reactive T cells correlated with a reduction (40%) in rate of
      relapse in RR-MS patients as compared with the pre-treatment rate in the same
      cohort. However, the reduction in EDSS was minimal in RR-MS patients while the
      EDSS was slightly increased in SP-MS patients over a period of 24 months. Serial
      semi-quantitative MRI examinations suggest stabilization in lesion activity as
      compared with baseline MRI. The findings suggest some potential clinical benefit
      of T cell vaccination in MS and encourage further investigations to evaluate the
      treatment efficacy of T cell vaccination in controlled trials.

PMID- 11985390
TI  - Facioscapulohumeral muscular dystrophy and myasthenia gravis co-existing in the
      same patient: a case report.

PMID- 11985391
TI  - Brain abscess developing at the site of preceding intracerebral hemorrhage.

PMID- 11985392
TI  - Successful treatment of a spontaneous cervical cerebrospinal fluid leak with a CT
      guided epidural blood patch.

PMID- 11985393
TI  - Neurocysticercosis: an unusual presentation of a rare disease.

PMID- 11985394
TI  - Marchiafava-Bignami disease with resolving symmetrical putaminal lesion.

PMID- 11985396
TI  - Herman Boerhaave (1668-1738).

PMID- 11985395
TI  - Painful neck stiffness secondary to an intramedullary abscess of the spinal cord
      in a HIV infected patient: a case report.

PMID- 11985398
TI  - At a crossroads: ADA and public policy.

PMID- 11985399
TI  - SI units revisited.

PMID- 11985400
TI  - Upcoming DRI report: new ways of defining fiber.

PMID- 11985401
TI  - Case management positions offer rewarding educational opportunities for
      registered dietitians.

PMID- 11985402
TI  - Eating disorders: a few more thoughts.

PMID- 11985403
TI  - Food industry's role in national nutrition policy: working for the common good.

PMID- 11985404
TI  - The impact of gaining provider status in the Medicare program. What all dietetics
      professionals need to know.

PMID- 11985405
TI  - Comparison of international food guide pictorial representations.

PMID- 11985406
TI  - High-soluble-fiber foods in conjunction with a telephone-based, personalized
      behavior change support service result in favorable changes in lipids and
      lifestyles after 7 weeks.
AB  - OBJECTIVE: To evaluate whether an intervention of foods high in soluble fiber
      from psyllium and/or oats plus a telephone-based, personalized behavior change
      support service improves serum lipids and elicits cholesterol-managing lifestyle
      changes vs usual care. DESIGN: 7-week randomized, controlled intervention.
      SUBJECTS/SETTING: 150 moderately hypercholesterolemic men and women, age range 25
      to 70 years. INTERVENTION: The intervention group consumed 4 servings/day of high
      fiber foods and had weekly telephone conversations with a personal coach who
      offered support and guidance in making lifestyle changes consistent with the
      National Cholesterol Education Program's (NCEP) cholesterol-lowering guidelines.
      The usual care group received a handout describing the NCEP Step-1 diet. MAIN
      OUTCOME MEASURES: Serum lipids and lipoproteins and self-reported lifestyle
      changes. STATISTICAL ANALYSES: For physiologic and dietary changes, mixed linear
      models for repeated measures were applied. Models were simplified using analysis
      of covariance where age in years was the covariate. Traditional general linear
      models were used to assess lifestyle changes. RESULTS: In the intervention group
      total cholesterol (TC) decreased 5.6%, low-density lipoprotein (LDL) cholesterol
      7.1%, LDL/high-density lipoprotein (HDL) cholesterol ratio 5.6%, and
      triglycerides (TG) 14.2% (P<.0167); decreases in TC and LDL were significantly
      different from the usual care group. In the usual care group TC decreased 1.9%,
      LDL 1.2%, LDL/HDL 1.9%, and TG 4.4% (all not significant). The intervention group
      also reported an increase in their knowledge, ability, and confidence to make
      cholesterol-managing diet and exercise changes compared with the usual care group
      (P<.05). The intervention group had a greater decrease in energy intake from
      saturated fat (-1.6%) and increase in soluble fiber intake (7.3%) than the usual
      care group (P<.05). The intervention group reported an increase in exercise vs
      the usual care group (P<.05). Both intervention and control groups had a minimal
      reduction (<1%) in body weight compared with baseline (P<.0167).
      APPLICATIONS/CONCLUSIONS: A 7-week intervention that includes both functional
      foods and individualized, interactive support for behavior change could be an
      effective model for dietitians to use with patients at risk for CVD, pending
      results of long-term studies.

PMID- 11985407
TI  - Serum cholesterol levels in children are associated with dietary fat and fatty
      acid intake.
AB  - BACKGROUND: Recent studies in adults suggest that individual dietary fatty acids
      differ markedly in their effects on serum lipids and lipoprotein levels. However,
      these associations have rarely been studied in children. OBJECTIVE: To assess,
      using regression procedures, the associations in children between specific fatty
      acids and nonfasting serum lipids and cholesterol after controlling for total
      energy and total fat intake, SUBJECTS: The sample consisted of 1,182 children who
      participated in the Child and Adolescent Trial for Cardiovascular Health. The
      sample was equally distributed across 4 sites (Louisiana, Texas, Minnesota,
      California). The sample was 48% boys; 71% white, 15% Hispanic-American, 10%
      African-American, 2% Asian, and 2% from other or unspecified racial/ethnic
      heritage. DESIGN: In this randomized multicenter trial with 56 intervention and
      40 control elementary schools, food record-assisted 24-hour dietary recalls and
      serum lipid measurements were collected for each child at baseline (3rd grade)
      and at the 5th grade follow-up. STATISTICAL ANALYSES: Repeated-measures analysis
      of variance was used to evaluate the association between nutrient composition of
      the diet and serum lipids. Independent dietary variables included amount and type
      of fat, individual fatty acids, protein, carbohydrate, and fiber. The dependent
      variables were the absolute values of serum total cholesterol (TC) and high
      density lipoprotein cholesterol (HDL-C) both at baseline (3rd grade) and at
      follow-up (5th grade). RESULTS: Increased total fat (b=0.053; P<.03) was
      associated with increased TC in the model when energy was held constant, whereas
      increased carbohydrate was associated with decreased TC (b=-0.021, P<.02) and HDL
      C (b=-0.010, P<.005) levels. Increased total protein (b=0.017, P<.05) was
      associated with increased HDL-C when energy was held constant. Saturated fat
      (b=0.004, P<.04), unsaturated fat (b=0.004, P<.03), and myristic fatty acid
      (b=0.021, P<.01) all increased TC in the model when total fat and total energy
      were held constant. CONCLUSIONS/APPLICATIONS: We conclude that using a modeling
      approach, the effect of diet on serum lipids in children is similar to that
      observed in adults. Total fat and saturated fat were positively associated with
      TC and HDLC levels, saturated fat was positively associated with TC, and
      carbohydrate was inversely associated with both TC and HDL-C. In the statistical
      model, substitution of unsaturated fatty acids, monounsaturated fatty acids, or
      oleic acid for saturated fat, while holding total fat and energy constant,
      slightly lowered TC. In contrast, substitution of total fat for carbohydrate in
      the model increased TC and, thus, did not seem to be associated with an apparent
      health advantage except for HDL-C elevating effects. However, consumption of
      individual fats tends to be highly correlated, and we were unable to determine if
      these biological effects were operating independently.

PMID- 11985408
TI  - Dietary patterns and nutrient intakes of 7-year-old children taking part in an
      atherosclerosis prevention project in Finland.
AB  - OBJECTIVE: To evaluate the dietary patterns of 7-year-old children participating
      in an atherosclerosis prevention project and the relationship of those dietary
      patterns to nutrient intakes and serum cholesterol values. DESIGN: In the
      randomized, prospective Special Turku Coronary Risk Factor Intervention Project
      (STRIP) 1,062 children were randomly assigned to an intervention group (n=540;
      low-saturated fat, low-cholesterol diet) or to a control group (n=522;
      unrestricted diet) at 7 months of age. SUBJECTS/SETTINGS: The intervention
      families received, at 6-month intervals, individualized counseling that focused
      on the known environmental atherosclerosis risk factors and aimed at reducing
      children's saturated fat and cholesterol intake. Nutrition counseling was
      targeted at the child but, because of the young age of the children, was given to
      the parents. When children were 7 years old, food and nutrient intakes of 307
      intervention and 323 control children were studied using 4-day food records.
      STATISTICAL ANALYSES PERFORMED: K-means cluster analysis was used to classify
      children into 4 groups on the basis of similarity of food intake. Differences in
      nutrient intakes and serum lipid concentrations between children in the 4 food
      intake clusters were evaluated using Tukey's multiple comparison test. RESULTS:
      Intervention children dominated the bread, skim milk, and margarine cluster and
      the cereals, rice, and pasta cluster whereas the 1.5%-fat milk and butter cluster
      included mainly control children. Saturated fat intake was nearest to the
      recommendations, that is 11.7% and 11.9% of energy, in the bread, skim milk, and
      margarine cluster and the cereals, rice, and pasta cluster, respectively.
      Children in the bread, skim milk, and margarine cluster had 20% to 27% higher
      fiber intakes (P<.001) whereas children in the sugar and sweets cluster had
      markedly higher sugar intakes than children in other clusters (P<.001). Serum
      cholesterol concentrations were lower in those clusters with high dietary ratios
      of polyunsaturated to saturated fat. CONCLUSION: Detailed and repeated dietary
      counseling of parents, starting when children are aged 7 months, that aims at
      decreasing children's exposure to known nutrition risk factors for coronary heart
      disease modifies children's food patterns and nutrient intakes toward expected
      values.

PMID- 11985409
TI  - Stability of ascorbic acid in commercially available orange juices.
AB  - OBJECTIVE: To compare the vitamin C content of reconstituted frozen orange juice
      concentrates at preparation to that of ready-to-drink orange juices purchased 4
      to 5 weeks from expiration. DESIGN: Juices were unsealed and analyzed for reduced
      and oxidized vitamin C content at the time of purchase and reanalyzed 3 times
      weekly for 4 to 5 weeks. Same-lot samples of the ready-to-drink juices remained
      sealed after purchase and were opened for analyses at 3, 2, 1, or 0 weeks before
      expiration. SAMPLES/SETTING: Orange juices were reconstituted frozen
      concentrates, ready-to-drink juice packaged in resealable, screw-top containers,
      or ready-to-drink juice packaged in nonresealable containers. Juices were
      obtained from local retailers and stored at 4 degrees C in their original
      containers when appropriate. STATISTICAL ANALYSES PERFORMED: The reduced vitamin
      C content of juices analyzed repeatedly, 3 times weekly for 4 weeks, were
      compared using repeated measures analysis of variance. Linear regression lines
      were computed for reduced vitamin C in each juice over time, and differences
      between slopes were analyzed by oneway analysis of variance. RESULTS: The orange
      juices from frozen concentrates contained 86 mg reduced vitamin C per fluid cup
      at initial preparation and 39 to 46 mg/c after 4 weeks of storage. Ready-to-drink
      juices averaged significantly lower reduced vitamin C: 27 to 65 mg/c at opening
      and 0 to 25 mg/c at expiration 4 weeks later. Ready-to-drink orange juices had
      twofold to threefold higher concentrations of oxidized vitamin C vs the orange
      juices reconstituted from frozen, and the decomposition rate of reduced vitamin C
      was similar for all juices, about 2% per day once opened. APPLICATIONS: Ready-to
      drink orange juices should be purchased 3 to 4 weeks before expiration date and
      consumed within 1 week of opening.

PMID- 11985410
TI  - Using Dietary Reference Intake-based methods to estimate the prevalence of
      inadequate nutrient intake among school-aged children.
AB  - OBJECTIVE: To estimate the prevalence of inadequate usual intakes of nutrients by
      school-aged children. DESIGN: A descriptive study using data from the US
      Department of Agriculture 1994 to 1996 Continuing Survey of Food Intake by
      Individuals. Each subject provided two 24-hour recalls. We adjusted for day-to
      day variation in nutrient intake and estimated the percentage of children with
      intakes below the Estimated Average Requirement (EAR) using the Software for
      Intake Distribution Estimation Program. SUBJECTS: A national sample of
      noninstitutionalized children aged 6 to 18 years (N=2,692). STATISTICAL ANALYSES:
      Chi2 tests showed that background characteristics or percentages with intakes
      below the EAR were the same across the 6 gender-age and racial/ethnic groups. The
      SUDAAN statistical package was used to account for the complex sample design.
      RESULTS: Usual intakes were more favorable for 5 B vitamins and iron than for the
      other nutrients examined. High percentages of children had intakes below the EAR
      for vitamin E. Many children aged 9 years and older had intakes below the EAR for
      folate and magnesium. Females aged 9 years and older had low calcium intakes
      relative to the Adequate Intake value. Females aged 14 to 18 years were at
      highest risk of usual intakes that did not meet the EARs. Few males in this age
      group met the EAR for vitamin E or magnesium. APPLICATIONS: Females aged 14 to
      18, in particular, should be targeted for efforts to improve nutrient intakes.
      Studies should monitor children's usual nutrient intakes after adjusting for day
      to-day variation.

PMID- 11985411
TI  - Question of the month. Does the alcohol used in cooking burn off completely?

PMID- 11985412
TI  - Coping with Prader-Willi syndrome.
AB  - Weight- and behavior-control issues are major concerns for parents of a child
      with Prader-Willi syndrome. However, limited information is available on how
      families implement the necessary dietary restrictions and the effects of the
      strategies. This study identified the advice a group of families received
      regarding weight management, the nutrition concerns they faced and how they coped
      with these concerns, and the effectiveness of their coping strategies. A 2-step
      survey methodology was used. Survey 1 identified the strategies parents used to
      cope with the feeding issues typically presented by children with Prader-Willi
      syndrome. Survey 2 evaluated the frequency with which these coping strategies
      were used and their effectiveness. Respondents also provided information on why
      strategies were not effective. Surveys were mailed to 496 parents/guardians of
      children (aged 25 years or younger) with Prader-Willi syndrome. A total of 293
      (64%) responded. Advice given to families centered on general weight management
      and dietary guidance. Difficulties centered around coping with food-related
      behaviors. Coping strategies varied; what worked for 1 family did not necessarly
      work for another. Participants indicated a desire to share experiences and a need
      for specific strategies to cope with feeding-behavior difficulties. A few basic
      behavior-management strategies, including successful use of incentives,
      responding to misbehavior, rewarding compliance with an exercise program, and
      modifying the behavior management when indicated, are briefly reviewed.

PMID- 11985413
TI  - Supervised practice preceptors' perceptions of rewards, benefits, support, and
      commitment to the preceptor role.

PMID- 11985414
TI  - The spoken menu concept of patient foodservice delivery systems increases overall
      patient satisfaction, therapeutic and tray accuracy, and is cost neutral for food
      and labor.

PMID- 11985415
TI  - High dietary fiber consumption is not associated with gastrointestinal discomfort
      in a diet intervention trial.

PMID- 11985416
TI  - Assessment of the diet quality of middle-aged and older adult Korean Americans
      living in Chicago.

PMID- 11985418
TI  - Assessment of nutrition education needs in an urban school district in
      Connecticut: establishing priorities through research.

PMID- 11985417
TI  - Dietary intakes of Native American children: findings from the pathways
      feasibility study.

PMID- 11985419
TI  - Regional body fat distribution and insulin resistance during adolescent
      pregnancy.

PMID- 11985420
TI  - 2002 accreditation standards for dietetics education.

PMID- 11985421
TI  - A problem-based nutrition care model that is diagnostic driven and allows for
      monitoring and managing outcomes.
AB  - The provision of quality food and nutrition services is at the core of dietetic
      practice. It is exciting to have the profession engaged in discussions regarding
      the development of a standardized care process/model to further enhance the
      quality of nutrition services. Educators, consultants, and practitioners have
      already spoken on behalf of such a tool. This article demonstrates how a
      systematic model, when incorporated into education and practice contributes to
      improved provision of MNT and adds value to the unique contributions of dietetic
      professionals. The authors hope that the discussion will continue and that more
      ideas and suggestions will be forthcoming.

PMID- 11985422
TI  - Intensive insulin therapy reduced mortality and morbidity in critically ill
      patients.

PMID- 11985423
TI  - Irbesartan was renoprotective in patients with type 2 diabetes, hypertension, and
      microalbuminuria.

PMID- 11985424
TI  - Irbesartan reduced progression of nephropathy caused by type 2 diabetes
      independent of the effect on blood pressure.

PMID- 11985425
TI  - Losartan was renoprotective in diabetic nephropathy independent of its effect on
      blood pressure.

PMID- 11985426
TI  - Review: recombinant human erythropoietin decreases the need for blood
      transfusions and may delay dialysis in chronic renal failure.

PMID- 11985427
TI  - Benzodiazepines were as safe as and more effective than placebo for out-of
      hospital status epilepticus.

PMID- 11985428
TI  - A specialist-nurse intervention reduced readmissions in patients hospitalized
      with chronic heart failure.

PMID- 11985429
TI  - Left ventricular assist devices reduced the risk for death and increased 1-year
      survival in chronic end-stage heart failure.

PMID- 11985430
TI  - Abciximab plus stenting reduced coronary events in patients with acute myocardial
      infarction.

PMID- 11985431
TI  - Early goal-directed therapy reduced mortality and multiorgan dysfunction in
      severe sepsis or septic shock.

PMID- 11985432
TI  - Review: hemoccult screening reduces death from colorectal cancer in average-risk
      patients > 50 years of age.

PMID- 11985433
TI  - Olsalazine was not better than placebo in maintaining remission in inactive Crohn
      disease.

PMID- 11985434
TI  - Enteral nutrition led to fewer postoperative complications than did parenteral
      feeding in gastrointestinal cancer.

PMID- 11985435
TI  - Nadolol and isosorbide prevented recurrent variceal bleeding better than did
      endoscopic ligation in cirrhosis.

PMID- 11985436
TI  - Lansoprazole provided more effective and faster relief for heartburn than did
      omeprazole in erosive esophagitis.

PMID- 11985437
TI  - Estrogen did not prevent death or nonfatal stroke in postmenopausal women with
      ischemic stroke or TIA.

PMID- 11985438
TI  - Review: adding newer disease-modifying drugs or biological agents to methotrexate
      improved rheumatoid arthritis symptoms.

PMID- 11985439
TI  - Review: etidronate decreases vertebral but not nonvertebral fractures in
      postmenopausal women.

PMID- 11985440
TI  - Review: adding antileukotrienes to inhaled corticosteroids reduces exacerbations
      in symptomatic chronic asthma.

PMID- 11985441
TI  - Review: exercise training reduces HbA1c levels but not body mass in type 2
      diabetes mellitus.

PMID- 11985442
TI  - Overall satisfaction increased more with inhaled insulin than with subcutaneous
      insulin in type 1 diabetes.

PMID- 11985443
TI  - Montelukast moderately decreased asthma symptoms in children with persistent
      asthma.

PMID- 11985444
TI  - Review: inactivated vaccines provide the greatest protection against influenza in
      healthy persons.

PMID- 11985445
TI  - Review: in relapsing-remitting multiple sclerosis, recombinant interferon reduces
      exacerbations in the first 2 treatment years.

PMID- 11985446
TI  - Review: haloperidol does not reduce agitation in dementia.

PMID- 11985447
TI  - Review: antidepressants increase remission and clinical improvement in bulimia
      nervosa.

PMID- 11985448
TI  - Review: psychological treatment is as effective as antidepressants for bulimia
      nervosa, but a combination is best.

PMID- 11985449
TI  - Review: primary care counseling improves psychological symptoms in patients with
      psychological and psychosocial problems.

PMID- 11985450
TI  - Initial bromocriptine did not change mortality in early, mild Parkinson disease.

PMID- 11985451
TI  - Review: pressurized metered-dose inhalers are as effective as other handheld
      inhalers for corticosteroid use in asthma.

PMID- 11985452
TI  - Review: pressurized metered-dose inhalers are as effective as other handheld
      inhalers for beta2-agonist bronchodilator use in asthma.

PMID- 11985453
TI  - Review: evidence on surgical interventions for distal radial fractures is
      inconclusive.

PMID- 11985454
TI  - Review: physical diagnostic tests have low diagnostic accuracy for meniscal
      lesions of the knee.

PMID- 11985455
TI  - Review: stress hyperglycemia after ischemic stroke indicates a greater risk for
      death in patients without diabetes.

PMID- 11985456
TI  - Review: breast cancer is associated with a family history of the disease in first
      degree relatives.

PMID- 11985457
TI  - 1 of 2 quality-improvement interventions for depression in managed care was more
      effective but more costly than usual care.

PMID- 11985458
TI  - Several simple rules predicted complications in high-risk patients with diabetes.

PMID- 11985459
TI  - Evidence-based medicine in practice.

PMID- 11985462
TI  - Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with
      potent antibacterial activity against gram-positive pathogens.
AB  - Potent nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase
      have been derived from a file compound high throughput screening hit. Optimized
      compounds show excellent antibacterial activity against staphylococcal and
      enterococcal pathogens, including strains resistant to clinical antibiotics.
      Compound 11 demonstrated in vivo efficacy in an S. aureus rat abscess infection
      model.

PMID- 11985463
TI  - Identification of a nonsteroidal liver X receptor agonist through parallel array
      synthesis of tertiary amines.
AB  - A potent, selective, orally active LXR agonist was identified from focused
      libraries of tertiary amines. GW3965 (12) recruits the steroid receptor
      coactivator 1 to human LXRalpha in a cell-free ligand-sensing assay with an
      EC(50) of 125 nM and profiles as a full agonist on hLXRalpha and hLXRbeta in cell
      based reporter gene assays with EC(50)'s of 190 and 30 nM, respectively. After
      oral dosing at 10 mg/kg to C57BL/6 mice, 12 increased expression of the reverse
      cholesterol transporter ABCA1 in the small intestine and peripheral macrophages
      and increased the plasma concentrations of HDL cholesterol by 30%. 12 will be a
      valuable chemical tool to investigate the role of LXR in the regulation of
      reverse cholesterol transport and lipid metabolism.

PMID- 11985464
TI  - Docking into knowledge-based potential fields: a comparative evaluation of
      DrugScore.
AB  - A new application of DrugScore is reported in which the knowledge-based pair
      potentials serve as objective function in docking optimizations. The Lamarckian
      genetic algorithm of AutoDock is used to search for favorable ligand binding
      modes guided by DrugScore grids as representations of the protein binding site.
      The approach is found to be successful in many cases where DrugScore-based re
      ranking of already docked ligand conformations does not yield satisfactory
      results. Compared to the AutoDock scoring function, DrugScore yields slightly
      superior results in flexible docking.

PMID- 11985465
TI  - Solid-phase library synthesis, screening, and selection of tight-binding reduced
      peptide bond inhibitors of a recombinant Leishmania mexicana cysteine protease B.
AB  - A one-bead-two-compound inhibitor library was synthesized by the split-mix method
      for the identification of inhibitors of a recombinant cysteine protease from
      Leishmania mexicana, CPB2.8DeltaCTE. The inhibitor library was composed of
      octapeptides with a centrally located reduced bond introduced by reductive
      amination of the resin-bound amines with Fmoc amino aldehydes. The library was
      screened on solid phase, and less than 1% of the library contained active
      compounds. The inhibitors displayed great specificity in the subsites flanking
      the enzyme catalytic triad with Cha and Ile/Leu preferred in P(2), Phe in P(1),
      Cha and Ile/Leu in P(1)', and Ile/Leu in P(2)'. Some of the inhibitors were
      resynthesized, and the kinetics of inhibition were determined in solution-phase
      assays. Most of the inhibitors had micromolar K(i) values, and a few inhibited
      the enzyme at nanomolar concentrations. One inhibitor, DKHF(CH(2)NH)LLVK (K(i) =
      1 microm), was tested for antiparasite efficacy and shown to affect parasite
      survival with an IC(50) of approximately 50 microm.

PMID- 11985466
TI  - Development of a combined protein and pharmacophore model for cytochrome P450
      2C9.
AB  - A combined protein and pharmacophore model for cytochrome P450 2C9 (CYP2C9) has
      been derived using various computational chemistry techniques. A combination of
      pharmacophore modeling (using 31 metabolic pathways for 27 substrates), protein
      modeling (using the rabbit CYP2C5/3 crystal structure), and molecular orbital
      calculations was used to derive a model that incorporated steric, electronic, and
      chemical stability properties. The initial pharmacophore model (based on a subset
      of 17 metabolic pathways for 16 substrates) and the protein model used to
      construct the combined model were derived independently and showed a large degree
      of complementarity. The combined model is in agreement with experimental results
      concerning the substrates used to derive the model and with site-directed
      mutagenesis data available for CYP2C9. The model has been successfully used to
      predict the metabolism of substrates not used to construct the model, of which
      four examples are discussed in detail. The model has also been successful in
      explaining the differences in substrate specificity between CYP2C9 and CYP2C19.

PMID- 11985467
TI  - Distribution of furamidine analogues in tumor cells: influence of the number of
      positive charges.
AB  - Fluorescence microscopy has been used to study the cellular distribution
      properties of a series of DNA binding cationic compounds related to the potent
      antiparasitic drug furamidine (DB75). The compounds tested bear a diphenylfuran
      or a phenylfuranbenzimidazole unfused aromatic core substituted with one or two
      amidine or imidazoline groups. The synthesis of five new compounds is reported.
      The B16 melanoma cell line was used to compare the capacities of mono-, bis-, and
      tetracations to enter the cell and nuclei. The high-resolution fluorescence
      pictures show that in the furamidine series, the compounds with two or four
      positive charges selectively accumulate in the cell nuclei whereas, in most
      cases, those bearing only one positive charge show reduced cell uptake
      capacities. One of the monocationic compounds, DB607, distributes in the
      cytoplasm, possibly in mitochondria, with no distinct nuclear accumulation. In
      sharp contrast, furamidine and benzimidazole analogues, including the drug DB293
      that forms DNA minor groove dimers, efficiently accumulate in the cell nuclei and
      the intranuclear distribution of these DNA minor groove binders is significantly
      different from that seen with the DNA intercalating drug propidium iodide. The
      results suggest that the presence of two amidine terminal groups plays a role in
      facilitating nuclear accumulation into cells, probably as a result of nucleic
      acid binding. The determination of DNA melting temperature increases on addition
      of these compounds supports the importance of DNA binding in nuclear uptake.

PMID- 11985468
TI  - Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and
      carbocyanine peptide-based optical contrast agents.
AB  - Site-specific delivery of drugs and contrast agents to tumors protects normal
      tissues from the cytotoxic effects of drugs and enhances the contrast between
      normal and pathologic tissues. One approach to achieve selectivity is to target
      overexpressed receptors on the membranes of tumor cells and to visualize the
      tumors by a noninvasive optical imaging method. Accordingly, we conjugated
      fluorescein and carbocyanine dyes to somatostatin and bombesin receptor-avid
      peptides and examined their receptor binding affinities. We also prepared
      potential dual imaging probes consisting of a bioactive peptide for tumor
      targeting, a biocompatible dye for optical imaging, and a radioactive or
      paramagnetic metal chelator for scintigraphic or magnetic resonance imaging of
      tumors. Using these approaches, the resulting carbocyanine derivatives of
      somatostatin and bombesin analogues retained high binding for their respective
      receptors. Further evaluation of representative molecules in rats bearing
      somatostatin- and bombesin-positive tumors showed selective uptake of the agents
      by the tumor cells. Unlike carbocyanine derivatives, the receptor binding of
      fluorescein-somatostatin peptide conjugates was highly sensitive to the type of
      linker and the site of fluorescein attachment on the nonreceptor binding region
      of the peptide. In general, the presence of flexible linkers disrupted binding
      affinity, possibly due to the interaction of the linker's thiourea group with the
      peptide's cyclic disulfide bond. While the receptor binding affinity of the dual
      probes was not dependent on the type of chelating group examined, it was affected
      by the relative positions of fluorescein and chelator on the lysine linker. For
      somatostatin compounds, best results were obtained when the chelator was on the
      alpha-amino lysine linker and fluorescein was on the epsilon-amino group. In
      contrast, conjugation of the chelator to epsilon- and fluorescein to the alpha
      amino lysine linker of bombesin peptides resulted in high receptor binding. These
      findings indicate that despite their small size, conjugation of dyes to truncated
      somatostatin and bombesin peptide analogues results in promising diagnostic
      agents that retain high receptor binding activity in vitro. The results further
      show that these contrast agents can selectively and specifically localize in
      receptor-positive tumors in rat models.

PMID- 11985469
TI  - Structure-based design of a parallel synthetic array directed toward the
      discovery of irreversible inhibitors of human rhinovirus 3C protease.
AB  - Utilizing the tools of parallel synthesis and structure-based design, a new class
      of Michael acceptor-containing, irreversible inhibitors of human rhinovirus 3C
      protease (HRV 3CP) was discovered. These inhibitors are shown to inhibit HRV-14
      3CP with rates of inactivation ranging from 886 to 31 400 M(-1) sec(-1). These
      inhibitors exhibit antiviral activity when tested against HRV-14 infected H1-HeLa
      cells, with EC(50) values ranging from 1.94 to 0.15 microM. No cytotoxicity was
      observed at the limits of the assay concentration. A crystal structure of one of
      the more potent inhibitors covalently bound to HRV-2 3CP is detailed. These
      compounds were also tested against HRV serotypes other than type 14 and were
      found to have highly variable activities.

PMID- 11985470
TI  - C-terminal cyclization of an SDF-1 small peptide analogue dramatically increases
      receptor affinity and activation of the CXCR4 receptor.
AB  - In an effort to improve the activities and bioavailabilities of stromal cell
      derived factor-1 (SDF-1, CXCL12) sdf-(1-67)-OH (1), we have prepared a linear
      peptide analogue [sdf-(1-31)-NH(2) (2)] and two lactam analogues [cyclo(Lys(20)
      Glu(24))-sdf-(1-31)-NH(2) (3) and cyclo(Glu(24)-Lys(28))-sdf-(1-31)-NH(2) (4)],
      consisting of the N-terminal region (amino acids 1-14) joined by a four-glycine
      linker to the C-terminal region (amino acids 56-67) of 1. Analogues 2 and 4 had
      eight residues of alpha-helix, as estimated from its circular dichroism (CD)
      spectra, in contrast to 10 residues in analogue 3. Cyclization of analogue 2 at
      residues 20 and 24 to give analogue 3 resulted in only a slight change to the
      theta;(222)/theta;(209) ratio (0.81 to 0.86, where 1.09 is considered a perfect
      alpha-helix), although an increase in the alpha-helix length of analogue 3 was
      observed. In contrast, cyclization between residues 24 and 28 by lactamization to
      give analogue 4 only slightly affected the helical content but clearly resulted
      in a more classical alpha-helical structure (theta;(222)/theta;(209) = 0.98).
      Cyclization of the linear analogue 2 enhanced the SDF-1 receptor CXCR4 binding
      approximately 114-fold, where the IC(50) values derived from (125)I-SDF-1
      competitive binding assays with CEM cells were found to be 39.5 +/- 5.9 nM, 28.9
      +/- 6.3 microM, 225.8 +/- 11.8 nM, and 254.1 +/- 5.4 nM for analogues 1-4,
      respectively. Intracellular calcium mobilization ([Ca(2+)](i)) induced after
      interaction with CXCR4, as measured by EC(50), was significantly reduced in
      analogue 4 compared to 3, and approached the EC(50) of native SDF-1, indicating a
      correlation between the degree of alpha-helix and biological activity. Therefore,
      the biological activity of small peptide SDF-1 analogues is highly dependent on
      the conformation of its C-terminal region.

PMID- 11985471
TI  - Design and synthesis of novel 5-substituted acyclic pyrimidine nucleosides as
      potent and selective inhibitors of hepatitis B virus.
AB  - A novel class of 5-substituted acyclic pyrimidine nucleosides, 1-[(2
      hydroxyethoxy)methyl]-5-(1-azidovinyl)uracil (9a), 1-[(2-hydroxy-1
      (hydroxymethyl)ethoxy)methyl]-5-(1-azidovinyl)uracil (9b), and 1-[4-hydroxy-3
      (hydroxymethyl)-1-butyl]-5-(1-azidovinyl)uracil (9c), were synthesized by
      regiospecific addition of bromine azide to the 5-vinyl substituent of the
      respective 5-vinyluracils (2a-c) followed by treatment of the obtained 5-(1-azido
      2-bromoethyl) compounds (3a-c) with t-BuOK, to affect the base-catalyzed
      elimination of HBr. Thermal decomposition of 9b and 9c at 110 degrees C in
      dioxane yielded corresponding 5-[2-(1-azirinyl)]uracil analogues (10b,c). The 5
      (1-azidovinyl)uracil derivatives 9a-c were found to exhibit potent and selective
      in vitro anti-HBV activity against duck hepatitis B virus (DHBV) infected primary
      duck hepatocytes at low concentrations (EC(50) = 0.01-0.1 microg/mL range). The
      most active anti-DHBV agent (9c), possessing a [4-hydroxy-3-(hydroxymethyl)-1
      butyl] substituent at N-1, exhibited an activity (EC(50) of 0.01-0.05 microg/mL)
      comparable to that of reference compound (-)-beta-L-2',3'-dideoxy-3'-thiacytidine
      (3-TC) (EC(50) = 0.01-0.05 microg/mL). In contrast, related 5-[2-(1
      azirinyl)]uracil analogues (10b,c) were devoid of anti-DHBV activity, indicating
      that an acyclic side chain at C-5 position of the pyrimidine ring is essential
      for anti-HBV activity. The pyrimidine nucleosides (9a-c, 10b,c) exhibited no
      cytotoxic activity against a panel of 60 human cancer cell lines. All of the
      compounds investigated did not show any detectable toxicity to several stationary
      and proliferating host cell lines or to mitogen stimulated proliferating human T
      lymphocytes, up to the highest concentration tested.

PMID- 11985472
TI  - Structure-activity relationships of a novel class of endothelin-A receptor
      antagonists and discovery of potent and selective receptor antagonist, 2
      (benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2H-chromene-3
      carboxylic acid (S-1255). 1. Study on structure-activity relationships and basic
      structure crucial for ET(A) antagonism.
AB  - A novel series of endothelin-A (ET(A)) selective receptor antagonists having a 2H
      chromene skeleton are described. A lead compound, 2-(benzo[1,3]dioxol-5-yl)-2H
      chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin
      II antagonist. A structure-activity relationship (SAR) study of 3 reveals that
      the structural requirements essential for potent and selective ET(A) receptor
      binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy
      groups at the 2-, 3-, and 6-positions, respectively, on the (R)-2H-chromene
      skeleton. The substituent at the 4-position is also important for improving the
      activity, and various hydrophobic functional groups of 6-9 A such as liner,
      branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups,
      and even halogen atoms were acceptable. These results suggest that (R)-2
      (benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108,
      is the crucial basic structure to be recognized by the ET(A) receptor. The most
      potent compound is (R)-48 (S-1255), which binds to the ET(A) receptor with an
      IC(50) value of 0.19 nM and is 630-fold selective for the ET(A) receptor than for
      the ET(B) receptor. This compound has 55% oral bioavailability in rats. On the
      basis of the SAR, the roles of each substituent in the receptor binding are
      discussed.

PMID- 11985473
TI  - Synthesis and biological evaluation of new citrate-based siderophores as
      potential probes for the mechanism of iron uptake in mycobacteria.
AB  - Several iron chelators containing alpha,beta-unsaturated hydroxamic acid motifs
      appended to a citric acid platform were synthesized. Mycobacterium
      paratuberculosis was then challenged to grow in the presence of a panel of
      siderophores (mycobactin J, deferrioxamine B, acinetoferrin, and nannochelin A)
      and the new synthetic agents. Of the structures tested, those containing the
      trans 2-octenoyl motif were preferred over those with trans cinnamoyl groups. In
      addition, derivatives containing longer tether lengths between the iron binding
      ligands (C5) were more efficacious and led to higher growth index values. Perhaps
      most remarkable was the finding that at 2.4 microM a trans 2-octenoylated,
      citrate-containing imide 6 was nearly 5-fold more effective in stimulating growth
      than the native chelator, mycobactin J. In this regard, new structural elements
      were identified (e.g., an imide motif or 2-octenoyl side chain), whose presence
      stimulated mycobacterial growth.

PMID- 11985474
TI  - Hematoporphyrin-derived soluble porphyrin-platinum conjugates with combined
      cytotoxic and phototoxic antitumor activity.
AB  - To combine the cytotoxic activity of cisplatin and the phototoxicicity of
      hematoporphyrin derivatives in the same molecule, hematoporphyrin was derivatized
      at the two secondary alcohol positions by etherification with oligo- and
      poly(ethylene glycol) units. The two carboxylic acid groups of the propionate
      side chains were used to bind platinum fragments. The antiproliferative activity
      of 35 platinum complexes (0.5, 1, and 5 microM) differing in solubility and type
      of the platinum fragment and the corresponding porphyrin ligands were studied in
      tests with TCC-SUP and J82 transitional bladder cancer cells in the dark and
      after irradiation (lambda = 600-730 nm, 24 J/cm(2)). The most active compounds
      were found among the porphyrin-platinum conjugates bearing the diammine and
      (RR/SS)-trans-1,2-diaminocyclohexane ligand. These porphyrin-platinum conjugates,
      especially the water-soluble species, such as diammine(7,12-bis[1-(poly(ethylene
      glycol)-750-monomethyl ether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18
      dipropionato)platinum(II), are promising candidates for the development of a
      novel type of photosensitizers with intrinsic cytotoxicity, which due to the
      porphyrin constituent may selectively enrich in tumor tissues.

PMID- 11985475
TI  - Soluble tetraarylporphyrin-platinum conjugates as cytotoxic and phototoxic
      antitumor agents.
AB  - A series of asymmetric tetraarylporphyrins was synthesized from pyrrole, para
      substituted oligo- or poly(ethylene glycol) monomethyl ether benzaldehyde and
      from 4-hydroxybenzaldehyde etherified with diethyl bromomalonate according to the
      Lindsey method. After hydrolysis of the tetraarylporphyrin esters, the resulting
      carboxylic acid groups were used to bind platinum fragments. In comparison to
      analogous hematoporphyrin-platinum conjugates, the title compounds are
      characterized by a 30 nm bathochromic shift of their absorption bands. The
      antiproliferative activity of 18 platinum complexes (1, 5, and 10 microM)
      differing in solubility, type of the platinum fragment, and the corresponding
      tetraarylporphyrin ligands were studied on TCC-SUP transitional bladder cancer
      cells in the dark and after irradiation (lambda = 600-730 nm; 24 J/cm(2)). The
      most active compounds were among the tetraarylporphyrin-platinum conjugates
      bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligands.

PMID- 11985476
TI  - Adenine nucleotide analogues locked in a Northern methanocarba conformation:
      enhanced stability and potency as P2Y(1) receptor agonists.
AB  - Preference for the Northern (N) ring conformation of the ribose moiety of
      nucleotide 5'-triphosphate agonists at P2Y(1), P2Y(2), P2Y(4), and P2Y(11)
      receptors, but not P2Y(6) receptors, was established using a ring-constrained
      methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J.
      Med. Chem. 2002, 45, 208-218.). We have now combined the ring-constrained (N)
      methanocarba modification of adenine nucleotides with other functionalities known
      to enhance potency at P2 receptors. The potency of the newly synthesized
      analogues was determined in the stimulation of phospholipase C through activation
      of turkey erythrocyte P2Y(1) or human P2Y(1) and P2Y(2) receptors stably
      expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue
      displayed an EC(50) at the hP2Y(1) receptor of 0.40 nM and was 55-fold more
      potent than the corresponding triphosphate and 16-fold more potent than the
      riboside 5'-diphosphate. 2-Cl-(N)-methanocarba-ATP and its N(6)-Me analogue were
      also highly selective, full agonists at P2Y(1) receptors. The (N)-methanocarba-2
      methylthio and 2-chloromonophosphate analogues were full agonists exhibiting
      micromolar potency at P2Y(1) receptors, while the corresponding ribosides were
      inactive. Although beta,gamma-methylene-ATP was inactive at P2Y receptors,
      beta,gamma-methylene-(N)-methanocarba-ATP was a potent hP2Y(1) receptor agonist
      with an EC(50) of 160 nM and was selective versus hP2Y(2) and hP2Y(4) receptors.
      The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues
      of AMP by rat 5'-ectonucleotidase were negligible. The rates of hydrolysis of the
      corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both
      isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis.
      The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was
      hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new,
      more stable and selective nucleotide agonists may be designed on the basis of the
      (N)-conformation, which greatly enhanced potency at P2Y(1) receptors.

PMID- 11985477
TI  - Design and synthesis of a novel series of 1,2-disubstituted cyclopentanes as
      small, potent potentiators of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4
      yl)propanoic acid (AMPA) receptors.
AB  - 2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) potentiators
      are ligands that act as positive allosteric modulators at the AMPA receptors. We
      recently disclosed a novel series of 2-arylpropylsulfonamides that were potent
      potentiators of responses mediated through AMPA receptors. To further define the
      structural requirements for activity in this series, new ring-constrained
      analogues were prepared and a new stereocenter was introduced. The potentiating
      activity was highly dependent on the stereochemistry at the 2-position of the
      disubstituted cyclopentane and was independent of the relative stereochemistry at
      the 1-position. Compound (R,R)-10 represents a potent, novel potentiator of
      iGluR4 flip receptors (EC(50) = 22.6 nM).

PMID- 11985478
TI  - A trypanocidal phenazine derived from beta-lapachone.
AB  - An intensive effort has been directed toward finding alternative drugs for
      treatment of Chagas' disease, caused by Trypanosoma cruzi, and prophylaxis of
      blood in endemic areas. Our research comprises the synthesis and trypanocidal
      screening of derivatives from naphthoquinones. Herein a new phenazine, obtained
      from the reaction of beta-lapachone with aniline, has its structure established
      by physical data and X-ray analysis. It was 9 times more active against T. cruzi
      trypomastigotes than crystal violet.

PMID- 11985479
TI  - Synthesis and in vitro evaluation of quaternary ammonium derivatives of
      chlorambucil and melphalan, anticancer drugs designed for the chemotherapy of
      chondrosarcoma.
AB  - To enhance affinity for malignant cartilaginous tumors (chondrosarcomas),
      quaternary ammonium (QA) conjugates of chlorambucil and melphalan were prepared
      by linking the QA moiety to nitrogen mustards via an amide bond. They exhibited
      closely similar and sometimes more favorable values than their parent compounds.
      In the cell lines tested, the two QA conjugates displayed appreciable
      cytotoxicity, the QA conjugate of chlorambucil even showing an enhanced
      efficiency against chondrosarcoma compared with chlorambucil.

PMID- 11985481
TI  - Adenoviruses in oncology: a viable option?
AB  - The feasibility of using adenoviruses for gene therapy has been under close
      scrutiny recently, as it has become clear that significant toxicity can result
      from the strong immune response created by intravenous administration of large
      doses of first generation adenovirus vectors. This suggests that other vectors
      could be more useful for treatment of metabolic and hereditary disease, where
      widespread transduction is often necessary for effective gene replacement, and
      the viability of target cells is important. However, promising recent results in
      human cancer trials have confirmed that adenoviruses can be very useful in
      oncology. For cancer treatment, the unparalleled transduction efficacy of
      adenovirus in dividing and dormant cells is a major benefit. As the goal in
      cancer gene therapy is to kill infected tumour cells, long-term transgene
      expression is not necessary. In addition, the immune response generated against
      infected cells could be useful for eradicating uninfected tumour. Importantly,
      more than 670 cancer patients have been treated with adenovirus intratumorally,
      intra-arterially, intraperitoneally and intravenously with very manageable
      adverse effects and no unexpected severe or lethal toxicity. Currently, the most
      promising approaches are based on replication-competent agents that allow
      efficient tumour penetration because of their capacity for tissue-specific
      replication. In addition to transcriptional control, it is becoming clear that
      targeting is necessary for efficient tumour transduction and less infection of
      normal tissues. Exciting results are anticipated when the first selectively
      replicating targeted adenoviruses go to clinical trials. In conclusion, intense
      gene therapy and virological research have suggested that while other vectors
      could be more useful for treatment of hereditary disease, adenoviruses are highly
      promising and safe agents for oncology, as suggested in a number of early phase
      clinical trials.

PMID- 11985482
TI  - The role of immune reconstitution in cytomegalovirus infection.
AB  - Cytomegalovirus (CMV) causes high morbidity and mortality in immunocompromised
      patients. The host immune response to CMV comprises specific and nonspecific
      cellular and humoral responses, but current knowledge supports a protective role
      only for cell-mediated immune responses. Although complete CMV eradication is
      unusual even in immunocompetent hosts, its morbidity can be limited by CMV
      specific CD8+ cytotoxic lymphocytes supported by CD4+-mediated T lymphocyte
      helper activity. In patients with congenital or acquired deficiencies of cell
      mediated immunity, recovery of CD4+ lymphocyte numbers and/or function coincides
      with cessation of CMV-associated morbidity. However, an immunological test that
      can predict protection against CMV disease across different types of high-risk
      patients is not yet available. In recent years, the introduction of antivirals
      active against CMV has improved the outcome of CMV disease. In addition, there is
      a continuous effort to develop CMV-specific immune-based therapies including
      vaccines and immune modulators such as cytokines, which may be of supplemental
      benefit in the control of CMV disease.

PMID- 11985483
TI  - Novel strategies for overcoming multidrug resistance in cancer.
AB  - The problems of why metastatic cancers develop pleiotropic resistance to all
      available therapies, and how this might be countered, are the most pressing in
      cancer chemotherapy. It is likely that such resistance involves a combination of
      mechanisms including changes in drug transport/drug targets, reduction in the
      degree of drug-induced apoptosis/cell loss, and increased rate of tumour
      repopulation following therapy. Current research must consider not only which
      mechanisms contribute, eventually relating this to individual patients with
      cancer, but also what strategies might be utilised to counter each of the
      important resistance mechanisms. A considerable amount of work has been devoted
      to the development of inhibitors of membrane-associated transport proteins such
      as P-glycoprotein, which mediate drug efflux. This work is now being complemented
      by approaches that target cell death pathways such as those mediated by release
      of mitochondrial proteins and by activation of surface receptors such as Fas.
      Rapid progress has been made in developing small-molecular-weight drugs that
      influence the rate of apoptosis, for instance by binding to the bcl-2 family of
      proteins regulating mitochondrial permeability. Antisense approaches aimed at
      reducing bcl-2 expression, and thus increasing the rate of cell death, are also
      showing promise. Modification of repopulation kinetics provides a further
      approach but has not received as much attention as other aspects of tumour
      resistance. New therapeutic approaches will have to be complemented by improved
      diagnostic tests to evaluate the contributions of different resistance mechanisms
      in individual patients with cancer.

PMID- 11985484
TI  - Peginterferon-alpha-2a (40kD) and ribavirin in patients with chronic hepatitis C:
      a phase II open-label study.
AB  - BACKGROUND AND AIMS: Addition of a 40kD polyethylene glycol moiety to interferon
      alpha-2a [peginterferon-alpha-2a (40kD)] improves pharmacokinetic properties over
      those of standard interferon. We conducted a phase II study to assess the safety
      and initial efficacy of peginterferon-alpha-2a (40kD) plus ribavirin combination
      therapy in patients with chronic hepatitis C (CHC). METHODS: Twenty patients
      received open-label 180 microg peginterferon-alpha-2a (40kD) subcutaneously once
      weekly and oral ribavirin 1000 or 1200mg daily for patients weighing <75 or > or
      =75kg, respectively, for a period of 24 weeks. Patients with hepatitis C virus
      (HCV) genotype 1 and a virological response at week 24 received study drugs for
      an additional 24 weeks. RESULTS: A sustained virological response, defined as
      undetectable HCV RNA 24 (i.e. <100 copies/ml) weeks after completing the therapy,
      was achieved in 50% of patients in an intent-to-treat analysis (6/16 genotype 1
      and 4/4 genotype non-1). Adverse events were similar to those reported with
      unmodified interferon plus ribavirin combination therapy. Anaemia led to
      ribavirin dose reduction in five patients. Neutropenia led to dose reduction in
      three patients treated with peginterferon-alpha-2a (40kD). CONCLUSIONS: The
      addition of ribavirin to a once-weekly peginterferon-alpha-2a (40kD) regimen
      should be investigated in larger clinical trials.

PMID- 11985485
TI  - Infliximab: an updated review of its use in Crohn's disease and rheumatoid
      arthritis.
AB  - Infliximab is a chimeric monoclonal antibody that binds to tumour necrosis factor
      alpha (TNFalpha) and neutralises its effects. TNFalpha plays an important role in
      the development of both Crohn's disease and rheumatoid arthritis. In a large,
      double-blind, randomised study involving patients with active, refractory Crohn's
      disease, significantly more recipients of intravenous infliximab, compared with
      placebo, achieved a clinical response after 4 weeks' follow-up. Moreover,
      infliximab administration was associated with a rapid improvement in endoscopic
      and histological findings in clinical trials involving patients with active,
      refractory Crohn's disease. The results of the A Crohn's Disease Clinical Trial
      Evaluating Infliximab in a New Long-Term Treatment Regimen (ACCENT) I study
      showed that maintenance infliximab therapy prolonged response and remission in
      patients with moderate to severe Crohn's disease. In patients with
      enterocutaneous fistulae associated with Crohn's disease who were involved in a
      double-blind, randomised study, significantly more patients who received multiple
      infusions of infliximab, compared with placebo, experienced a > or=50% reduction
      from baseline in the number of draining fistulae at > or =2 consecutive study
      visits. In patients with active rheumatoid arthritis refractory to treatment with
      methotrexate who were enrolled in a large, double-blind, randomised study [the
      Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study],
      American College of Rheumatology (ACR) 20, 50 and 70% response rates were seen in
      significantly more patients who received multiple infusions of infliximab plus
      methotrexate, compared with methotrexate plus placebo, after 30 and 54 weeks'
      treatment. Moreover, the ACR 20% response rate was maintained after 102 weeks'
      treatment. In addition, significantly less radiographic progression was seen in
      infliximab plus methotrexate, compared with methotrexate plus placebo, recipients
      after 54 weeks' treatment. Infliximab therapy was also associated with
      improvements in health-related quality of life in patients with Crohn's disease
      or rheumatoid arthritis. Infliximab was generally well tolerated in clinical
      trials with the most common adverse events including upper respiratory tract
      infection, headache, nausea, coughing, sinusitis and diarrhoea. Infliximab
      therapy may be associated with an increased risk of reactivation of tuberculosis
      in patients with latent disease. In conclusion, infliximab is an important
      treatment option in patients with active Crohn's disease who have not responded
      to conventional therapy and in patients with Crohn's disease who have fistulae.
      Moreover, infliximab plus methotrexate is effective in patients with active
      rheumatoid arthritis who have not responded adequately to traditional disease
      modifying antirheumatic drugs, in terms of reducing symptoms and signs, improving
      physical function and delaying the progression of structural damage.

PMID- 11985486
TI  - Angiotensin converting enzyme gene insertion/deletion polymorphism and
      cardiovascular disease: therapeutic implications.
AB  - Cardiovascular disease is the major cause of morbidity and mortality in
      Westernised societies. It is well known that the aetiology of this devastating
      disorder involves both genetic and environmental factors. Sequence variants of
      the components of the renin-angiotensin-aldosterone system and the kallikrein
      kinin system are suggested to have significant influences on cardiovascular
      homeostasis. Both gene targeting and transgenic studies in mice have clearly
      suggested a critical role of the angiotensin converting enzyme (ACE) gene in
      blood pressure regulation. Furthermore, an up-regulation of myocardial ACE gene
      expression has been observed in patients with heart failure. Thus, the ACE gene
      has been recognised as a top candidate gene for cardiovascular research. Over the
      past decade, the insertion/deletion (I/D) polymorphism of a 287-bp Alu element in
      intron 16 of the ACE gene has attracted significant attention and has been
      extensively investigated in a spectrum of cardiovascular phenotypes, because of
      its correlation with serum ACE activity. A large majority of previous studies
      have shown a positive association between the DD genotype and an increased risk
      of myocardial infarction, but results in hypertension, left ventricular
      hypertrophy, cardiomyopathy and restenosis after percutaneous transluminal
      coronary angioplasty remain quite controversial. Since ACE inhibitors are widely
      used in hypertension and congestive heart failure, we also review the literature
      on the relationship of ACE I/D polymorphism with ACE inhibitor response. It
      appears that this polymorphism has some moderate impact on the cardiovascular
      response to ACE inhibitors but there is no consensus as to which allele confers a
      more pronounced effect. In addition, previous data are suggestive of an
      association between the ACE I allele and a greater risk of increased occurrence
      of ACE inhibitor-induced cough, but such a relationship needs further
      confirmation. Overall, since ACE I/D is only an intronic marker, the true locus
      that controls the ACE enzyme activity remains to be identified, and could be
      located within either the ACE gene or another nearby gene such as the human
      growth hormone gene. We note that since associations tend to vary across
      different gender or ethnic groups, or across different socio-ecological settings,
      consideration of potential gene-gene and gene-environment interactions should be
      made. Furthermore, the dissection of the genetic underpinning of cardiovascular
      disease needs delineation of all molecular variants of the key physiological
      pathways that influence cardiovascular function.

PMID- 11985487
TI  - Options for induction immunosuppression in liver transplant recipients.
AB  - Immunosuppression administered in the early postoperative period following liver
      transplantation plays a crucial role in the survival of the graft and the
      patient. The introduction of cyclosporin was an important landmark in
      transplantation, and to this day, calcineurin inhibitors form the basis of most
      induction immunosuppression regimens. New drugs are being developed which are
      more specifically targeted to prevention of rejection, and multiple drug
      combinations have been proposed as a means of reducing the adverse effects of
      individual drugs. Azathioprine and the newer antimetabolite mycophenolate mofetil
      have been added to calcineurin inhibitor-based regimens with varying amounts of
      success. Antibody induction has evolved as a potent form of immunosuppression as
      well as a means of avoiding certain adverse effects, particularly nephrotoxicity.
      The numerous adverse effects encountered with polyclonal preparations have been
      reduced with the development of more specific monoclonal antibodies such as
      muromonab CD3 (OKT3) or interleukin (IL)-2 receptor (IL-2R) antagonists. The anti
      IL-2R antibody preparations basiliximab and daclizumab have shown excellent early
      results due to their potent yet highly targeted immunosuppressive effect and
      minimal adverse effects. Further study is needed to determine the most
      appropriate dosage, timing and patient population for these new drugs in the
      setting of liver transplantation. Although a number of different induction
      regimens have been described, no single protocol is suitable for all liver
      transplant recipients. Rather, certain regimens have advantages that could favour
      their use in a specific subgroup of patients. A number of clinical trials are
      underway to identify new, more specific drugs and combinations which could be
      useful in induction immunosuppression.

PMID- 11985488
TI  - Pharmacoeconomics of influenza vaccination for healthy working adults: reviewing
      the available evidence.
AB  - A favourable pharmacoeconomic profile has been well established for influenza
      vaccination in the elderly. For employers relevant benefits seem to exist for
      vaccinating healthy working adults to avert absenteeism and related production
      losses. From a pharmacoeconomic point of view it is relevant to consider whether
      societal benefits of vaccination for healthy working adults is worthwhile given
      the costs of vaccination for the community. We searched Medline and Embase using
      the key words influenza (vaccination) in combination with cost, cost-benefit,
      cost-effectiveness, efficiency, economic evaluation, health-policy and
      pharmacoeconomics. From this primary search, we selected 11 studies concerned
      with the group of healthy working adults. We reviewed these studies according to
      several criteria: benefit-to-cost (B/C) ratio;vaccine effectiveness, influenza
      incidence, number of days of work absence due to illness; and relative cost of
      the vaccine. Three studies on vaccinating healthy working adults found costs
      exceeding the benefits (B/C-ratio <1). The remaining eight pharmacoeconomic
      studies found a B/C-ratio of almost two or more. Cost savings are strongly
      related to the inclusion of indirect benefits related to averted production
      losses. After exclusion of indirect costs and benefits of production
      gains/losses, only one of the eight studies remains cost saving. Considering the
      available pharmacoeconomic evidence, vaccination of healthy working adults in
      Western countries may be an intervention with favourable cost-effectiveness and
      cost-saving potentials if indirect benefits of averted production losses are
      included. Excluding indirect benefits and costs of production losses/gains, cost
      saving potentials are limited. Recent international guidelines for
      pharmacoeconomic research advise the inclusion of production gains and losses in
      the preferred societal perspective. Hence, on the basis of the available
      evidence, influenza vaccination of healthy working adults may be recommended from
      pharmacoeconomic point of view. Pharmacoeconomics do, however, present only one
      argument for consideration aside from ethical issues, budgetary limits and
      psychosocial aspects.

PMID- 11985489
TI  - Mechanisms of fungal resistance: an overview.
AB  - The increased use of antifungal agents in recent years has resulted in the
      development of resistance to these drugs. The significant clinical implication of
      resistance has led to heightened interest in the study of antifungal resistance
      from different angles. In this article we discuss antifungal susceptibility
      testing, the mode of action of antifungals and mechanisms of resistance.
      Antifungals are grouped into five groups on the basis of their site of action:
      azoles, which inhibit the synthesis of ergosterol (the main fungal sterol);
      polyenes, which bind to fungal membrane sterol, resulting in the formation of
      aqueous pores through which essential cytoplasmic materials leak out;
      allylamines, which block ergosterol biosynthesis, leading to accumulation of
      squalene (which is toxic to the cells); candins (inhibitors of the fungal cell
      wall), which function by inhibiting the synthesis of beta 1,3-glucan (the major
      structural polymer of the cell wall); and flucytosine, which inhibits
      macromolecular synthesis. Different mechanisms contribute to the resistance of
      antifungal agents. These mechanisms include modification of ERG11 gene at the
      molecular level (gene mutation, conversion and overexpression), over expression
      of specific drug efflux pumps, alteration in sterol biosynthesis, and reduction
      in the intracellular concentration of target enzymes. Approaches to prevent and
      control the emergence of antifungal resistance include prudent use of
      antifungals, treatment with the appropriate antifungal and conducting
      surveillance studies to determine the frequency of resistance.

PMID- 11985491
TI  - Esomeprazole: a review of its use in the management of acid-related disorders in
      the US.
AB  - Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to
      be developed as a single optical isomer. It provides better acid control than
      current racemic proton pump inhibitors and has a favourable pharmacokinetic
      profile relative to omeprazole. In large well designed 8-week trials in patients
      with erosive oesophagitis, esomeprazole recipients achieved significantly higher
      rates of endoscopically confirmed healed oesophagitis than those receiving
      omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades
      of oesophagitis; notably, relative to lansoprazole, as the baseline severity of
      disease increased, the difference in rates of healed oesophagitis also increased
      in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole
      40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole
      recipients (20mg once daily). In a study in >5000 patients, respective healed
      oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were
      92.6 and 88.8%. Resolution of heartburn was also significantly better with
      esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12
      months) therapy with esomeprazole effectively maintained healed oesophagitis in
      these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective
      in patients with symptomatic gastro-oesophageal reflux disease (GORD) without
      oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to
      successfully managing duodenal ulcer disease. Ten days' triple therapy
      (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin
      500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with
      endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well
      tolerated, both as monotherapy and in combination with antimicrobial agents. The
      tolerability profile is similar to that of other proton pump inhibitors. Few
      patients discontinued therapy because of treatment-emergent adverse events (<3%
      of patients) and very few (<1%) drug-related serious adverse events were
      reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment
      for managing GORD and for eradicating H. pylori infection in patients with
      duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively
      healed oesophagitis and resolved symptoms in patients with endoscopically
      confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind
      trials, esomeprazole provided significantly better efficacy than omeprazole or
      lansoprazole in terms of both healing rates and resolution of symptoms. Long-term
      therapy with esomeprazole effectively maintained healed oesophagitis in these
      patients. Esomeprazole was also effective in patients with symptomatic GORD.
      Thus, esomeprazole has emerged as an effective option for first-line therapy in
      the management of acid-related disorders.

PMID- 11985493
TI  - Post-translational integration and oligomerization of connexin 26 in plasma
      membranes and evidence of formation of membrane pores: implications for the
      assembly of gap junctions.
AB  - Gap-junction channels provide a widespread intercellular signalling mechanism.
      They are constructed of a family of connexin membrane proteins that thread across
      the membrane four times and oligomerize to generate hexameric gap-junction
      hemichannels. Using an in vitro cell-free transcription/translation system, we
      demonstrate that connexin (Cx) 26, one of the smallest connexins, is integrated
      directly in a post-translational manner into plasma membranes. Protein-cleavage
      studies of Cx26 integrated into plasma membranes indicate a similar native
      transmembrane topography to that of Cx26 integrated co-translationally into
      microsomes. Cx26 integrated post-translationally into plasma membranes
      oligomerizes and, when incorporated into liposomes, provides permeability to
      ascorbic acid, suggesting that gap-junction hemichannels are generated. The
      results provide the basis of a novel alternative mechanism for spontaneous
      assembly in plasma membranes of Cx26 gap-junction hemichannels that occurs
      independently of the conventional biogenesis of gap junctions involving connexin
      trafficking and oligomerization via membrane components of the secretory pathway.

PMID- 11985492
TI  - Probing the catalytic mechanism of Escherichia coli amine oxidase using
      mutational variants and a reversible inhibitor as a substrate analogue.
AB  - Copper amine oxidases are homodimeric enzymes containing one Cu(2+) ion and one
      2,4,5-trihydroxyphenylalanine quinone (TPQ) per monomer. Previous studies with
      the copper amine oxidase from Escherichia coli (ECAO) have elucidated the
      structure of the active site and established the importance in catalysis of an
      active-site base, Asp-383. To explore the early interactions of substrate with
      enzyme, we have used tranylcypromine (TCP), a fully reversible competitive
      inhibitor, with wild-type ECAO and with the active-site base variants D383E and
      D383N. The formation of an adduct, analogous to the substrate Schiff base,
      between TCP and the TPQ cofactor in the active site of wild-type ECAO and in the
      D383E and D383N variants has been investigated over the pH range 5.5-9.4. For the
      wild-type enzyme, the plot of the binding constant for adduct formation (K(b))
      against pH is bell-shaped, indicating two pK(a)s of 5.8 and approximately 8,
      consistent with the preferred reaction partners being the unprotonated active
      site base and the protonated TCP. For the D383N variant, the reaction pathway
      involving unprotonated base and protonated TCP cannot occur, and binding must
      follow a less favoured pathway with unprotonated TCP as reactant. Surprisingly,
      for the D383E variant, the K(b) versus pH behaviour is qualitatively similar to
      that of D383N, supporting a reaction pathway involving unprotonated TCP. The TCP
      binding data are consistent with substrate binding data for the wild type and the
      D383E variant using steady-state kinetics. The results provide strong support for
      a protonated amine being the preferred substrate for the wild-type enzyme, and
      emphasize the importance of the active-site base, Asp-383, in the primary binding
      event.

PMID- 11985494
TI  - Mapping the human translation elongation factor eEF1H complex using the yeast two
      hybrid system.
AB  - In eukaryotes, the eukaryotic translation elongation factor eEF1A responsible for
      transporting amino-acylated tRNA to the ribosome forms a higher-order complex,
      eEF1H, with its guanine-nucleotide-exchange factor eEF1B. In metazoans, eEF1B
      consists of three subunits: eEF1B alpha, eEF1B eta and eEF1B gamma. The first two
      subunits possess the nucleotide-exchange activity, whereas the role of the last
      remains poorly defined. In mammals, two active tissue-specific isoforms of eEF1A
      have been identified. The reason for this pattern of differential expression is
      unknown. Several models on the basis of in vitro experiments have been proposed
      for the macromolecular organization of the eEF1H complex. However, these models
      differ in various aspects. This might be due to the difficulties of handling,
      particularly the eEF1B beta and eEF1B gamma subunits in vitro. Here, the human
      eEF1H complex is for the first time mapped using the yeast two-hybrid system,
      which is a powerful in vivo technique for analysing protein-protein interactions.
      The following complexes were observed: eEF1A1:eEF1B alpha, eEF1A1:eEF1B beta,
      eEF1B beta:eEF1B beta, eEF1B alpha:eEF1B gamma, eEF1B beta:eEF1B gamma and eEF1B
      alpha:eEF1B gamma:eEF1B beta, where the last was observed using a three-hybrid
      approach. Surprisingly, eEF1A2 showed no or only little affinity for the guanine
      nucleotide-exchange factors. Truncated versions of the subunits of eEF1B were
      used to orientate these subunits within the resulting model. The model unit is a
      pentamer composed of two molecules of eEF1A, each interacting with either eEF1B
      alpha or eEF1B beta held together by eEF1B gamma. These units can dimerize via
      eEF1B beta. Our model is compared with other models, and structural as well as
      functional aspects of the model are discussed.

PMID- 11985495
TI  - The p55 tumour necrosis factor receptor TNFR1 contains a trans-Golgi network
      localization signal in the C-terminal region of its cytoplasmic tail.
AB  - It has been reported in some human cells that, in addition to a plasma membrane
      localization, members of the tumour necrosis factor receptor superfamily may be
      localized to the Golgi complex. We have shown by immunofluorescence and
      immunoelectron microscopy that the p55 tumour necrosis factor receptor, TNFR1, is
      principally localized to the trans-Golgi network in the human breast carcinoma
      cell line, MCF7. Chimaeras consisting of the extracellular and transmembrane
      domains of CD8 together with the cytoplasmic tail of TNFR1 were targeted to the
      trans-Golgi network in stably transfected rat fibroblastic cells. Deletions in
      the cytoplasmic tails of these chimaeras demonstrated the requirement for the C
      terminal sequence of 23 amino acids for this targeting. The 23 amino acid
      sequence is mostly outside the death domain and contains both an acid patch and a
      dileucine motif. Interaction of this sequence with membrane traffic adaptor
      proteins may play an important role in controlling the responses of cells to
      tumour necrosis factor, since binding of signalling adaptor proteins has only
      been demonstrated for plasma membrane, and not Golgi-localized, TNFR1.

PMID- 11985490
TI  - Ceftriaxone: an update of its use in the management of community-acquired and
      nosocomial infections.
AB  - Ceftriaxone is a parenteral third-generation cephalosporin with a long
      elimination half-life which permits once-daily administration. It has good
      activity against Streptococcus pneumoniae, methicillin-susceptible staphylococci,
      Haemophilus influenzae, Moraxella catarrhalis and Neisseria spp. Although active
      against Enterobacteriaceae, the recent spread of derepressed mutants which
      hyperproduce chromosomal beta-lactamases and extended-spectrum beta-lactamases
      has diminished the activity of all third-generation cephalosporins against these
      pathogens necessitating careful attention to sensitivity studies. Extensive data
      from randomised clinical trials confirm the efficacy of ceftriaxone in serious
      and difficult-to-treat community-acquired infections including meningitis,
      pneumonia and nonresponsive acute otitis media. Ceftriaxone also has efficacy in
      other community-acquired infections including uncomplicated gonorrhoea, acute
      pyelonephritis and various infections in children. In the nosocomial setting,
      extensive data also confirm the efficacy of ceftriaxone with or without an
      aminoglycoside in serious Gram-negative infections, pneumonia, spontaneous
      bacterial peritonitis and as surgical prophylaxis. Outpatient use of ceftriaxone,
      either as part of a step-down regimen or parenterally, is a distinguishing
      feature of the data gathered on the agent over the last decade. The review
      focuses on new applications of the drug and its use in infections in which the
      causative pathogens or their resistance patterns have changed over the past
      decade. Ceftriaxone has a good tolerability profile, the most common events being
      diarrhoea, nausea, vomiting, candidiasis and rash. Ceftriaxone may cause
      reversible biliary pseudolithiasis, notably at higher dosages of the drug (>/=2
      g/day); however, the incidence of true lithiasis is <0.1%. Injection site
      discomfort or phlebitis can occur after intramuscular or intravenous
      administration. CONCLUSIONS: As a result of its strong activity against S.
      pneumoniae, ceftriaxone holds an important place, either alone or as part of a
      combination regimen, in the treatment of invasive pneumococcal infections,
      including those with reduced beta-lactam susceptibility. Its once-daily
      administration schedule allows simplification of otherwise complex regimens in a
      hospital setting and has also contributed to its popularity as a parenteral agent
      in an ambulatory setting. These properties, together with a well characterised
      tolerability profile, mean that ceftriaxone is likely to retain its place as an
      important third-generation cephalosporin in the treatment of serious community
      acquired and nosocomial infections.

PMID- 11985496
TI  - The C-terminal, third conserved motif of the protein activator PACT plays an
      essential role in the activation of double-stranded-RNA-dependent protein kinase
      (PKR).
AB  - One of the key mediators of the antiviral and antiproliferative actions of
      interferon is double-stranded-RNA-dependent protein kinase (PKR). PKR activity is
      also involved in the regulation of cell proliferation, apoptosis and signal
      transduction. We have recently identified PACT, a novel protein activator of PKR,
      as an important modulator of PKR activity in cells in the absence of viral
      infection. PACT heterodimerizes with PKR and activates it by direct protein
      protein interactions. Endogenous PACT acts as an activator of PKR in response to
      diverse stress signals, such as serum starvation and peroxide or arsenite
      treatment, and is therefore a novel, stress-modulated physiological activator of
      PKR. In this study, we have characterized the functional domains of PACT that are
      required for PKR activation. Our results have shown that, unlike the N-terminal
      conserved domains 1 and 2, the third conserved domain of PACT is dispensable for
      its binding of double-stranded RNA and inter action with PKR. However, a deletion
      of domain 3 results in a loss of PKR activation ability, in spite of a normal
      interaction with PKR, thereby indicating that domain 3 plays an essential role in
      PKR activation. Purified recombinant domain 3 could also activate PKR efficiently
      in vitro. Our results indicate that, although dispensable for PACT's high
      affinity interaction with PKR, the third motif is essential for PKR activation.
      In addition, domain 3 and eukaryotic initiation factor 2alpha both interact with
      PKR through the same region within PKR, which we have mapped to lie between amino
      acid residues 318 and 551.

PMID- 11985497
TI  - RGS3 interacts with 14-3-3 via the N-terminal region distinct from the RGS
      (regulator of G-protein signalling) domain.
AB  - RGS3 belongs to a family of the regulators of G-protein signalling (RGS), which
      bind and inhibit the G alpha subunits of heterotrimeric G-proteins via a
      homologous RGS domain. Increasing evidence suggests that RGS proteins can also
      interact with targets other than G-proteins. Employing yeast two-hybrid screening
      of a cDNA library, we identified an interaction between RGS3 and the
      phosphoserine-binding protein 14-3-3. This interaction was confirmed by in vitro
      binding and co-immunoprecipitation experiments. RGS3-deletion analysis revealed
      the presence of a single 14-3-3-binding site located outside of the RGS domain.
      Ser(264) was then identified as the 14-3-3-binding site of RGS3. The S(264)A
      mutation resulted in the loss of RGS3 binding to 14-3-3, without affecting its
      ability to bind G alpha(q). Signalling studies showed that the S(264)A mutant was
      more potent than the wild-type RGS3 in inhibition of G-protein-mediated
      signalling. Binding experiments revealed that RGS3 exists in two separate pools,
      either 14-3-3-bound or G-protein-bound, and that the 14-3-3-bound RGS3 is unable
      to interact with G-proteins. These data are consistent with the model wherein 14
      3-3 serves as a scavenger of RGS3, regulating the amounts of RGS3 available for
      binding G-proteins. This study describes a new level in the regulation of G
      protein signalling, in which the inhibitors of G-proteins, RGS proteins, can
      themselves be regulated by phosphorylation and binding 14-3-3.

PMID- 11985498
TI  - Inhibition of potato lipoxygenase by linoleyl hydroxamic acid: kinetic and EPR
      spectral evidence for a two-step reaction.
AB  - The reaction mechanism of an electrophoretically pure potato tuber lipoxygenase
      (ptLOX) was studied by EPR spectroscopy. An EPR spectrum of the 'native' ptLOX
      recorded at 4.5+/-0.5 K showed signals of a high-spin (pseudo) axial Fe(3+) with
      a g-value of approx. 6.3+/-0.1 with a shoulder at g=5.9+/-0.1, and a rhombic
      Fe(3+) signal at g=4.35+/-0.05. When the enzyme was treated with a 2-fold molar
      excess of 13(S)-hydroperoxyoctadecadienoic acid [13(S)-HPODE], a 3-fold increase
      in the integral intensity of the g=6.3 signal was observed, indicating that 25%
      of the native ptLOX iron was in ferrous state. The positional isomer 9(S)-HPODE
      caused similar spectral changes. Therefore the catalytic centre of ptLOX appears
      to accommodate both positional isomers of linoleic acid hydroperoxides in a
      manner that ensures proper alignment of their hydroperoxy groups with the iron
      centre of the enzyme. Treatment of the Fe(3+)-ptLOX form with a 3-fold molar
      excess of linoleyl hydroxamic acid (LHA) completely quenched the g=6.3 signal.
      Concurrently, a dramatic increase in the signal at g=4.35 was detected, which was
      attributed to a newly formed LHA-Fe(3+)-ptLOX complex. The spectral
      characteristics of the complex are similar to those of a 4-nitrocatechol-Fe(3+)
      ptLOX complex. From these observations, we conclude that LHA did not reduce
      Fe(3+) to Fe(2+), but rather formed a LHA-Fe(3+)-ptLOX complex. Formation of such
      a complex may be responsible for the inhibitory activity of LHA, at least in the
      initial stages of enzyme inhibition. A prolonged 15 min incubation of the complex
      at 23+/-1 degrees C led to the partial quenching of the g=4.35 signal. The
      quenching is attributed to the reduction of Fe(3+)-ptLOX by LHA, with concomitant
      formation of its oxidation product(s). A kinetic scheme for the inhibition is
      proposed.

PMID- 11985510
TI  - Cellular immune responses against hepatitis C virus: the evidence base 2002.
AB  - Hepatitis C virus (HCV) is an RNA virus which is estimated to persistently infect
      about 170 million people worldwide. After acute infection, there is an initial
      period during which long-term outcome is decided. There is strong evidence that
      the cellular immune responses, involving both CD4+ and CD8+ T lymphocytes, are
      involved at this stage and it is their effectiveness which determines outcome.
      What is not understood is what determines their effectiveness. The most important
      component of this is likely to be some aspect of epitope selection, itself
      dictated by host MHC. Thus, to understand host immunity to HCV, we need to have a
      detailed understanding of the peptides involved in T lymphocyte responses. In
      this review, we discuss the peptide epitopes that have been identified so far,
      and their potential significance. We relate this to a scheme of host defence
      which may be useful for understanding natural and vaccine-induced immunity.

PMID- 11985511
TI  - Treatment of autoimmune diabetes recurrence in non-obese diabetic mice by mouse
      interferon-beta in combination with an analogue of 1alpha,25-dihydroxyvitamin-D3.
AB  - Autoimmune diabetes recurrence is in part responsible for islet graft destruction
      in type 1 diabetic individuals. The aim of the present study was to design
      treatment modalities able to prevent autoimmune diabetes recurrence after islet
      transplantation in spontaneously diabetic NOD mice. In order to avoid confusion
      between autoimmune diabetes recurrence and allograft rejection, we performed
      syngeneic islet transplantations in spontaneously diabetic NOD mice. Mice were
      treated with mouse interferon-beta (IFN-beta, 1 x 105 IU/day), a new 14-epi-1,25
      (OH)2D3-analogue (TX 527, 5 microg/kg/day) and cyclosporin A (CsA, 7.5 mg/kg/day)
      as single substances and in combinations. Treatment was stopped either 20 days
      (IFN-beta and CsA) or 30 days (TX 527) after transplantation. Autoimmune diabetes
      recurred in 100% of control mice (MST 11 days). None of the mono-therapies
      significantly prolonged islet graft survival. Combining CsA with TX 527
      maintained graft function in 67% of recipients as long as treatment was given
      (MST 31 days, P < 0.01 versus controls). Interestingly, 100% of the IFN-beta plus
      TX 527-treated mice had normal blood glucose levels during treatment, and even
      had a more pronounced prolongation of graft survival (MST 62 days, P < 0.005
      versus controls). Cytokine mRNA analysis of the grafts 6 days after
      transplantation revealed a significant decrease in IL-2, IFN-gamma and IL-12
      messages in both IFN-beta plus TX 527- and CsA plus TX 527-treated mice, while
      only in the IFN-beta with TX 527 group were higher levels of IL-10 transcripts
      observed. Therefore, we conclude that a combination of IFN-beta and TX 527 delays
      autoimmune diabetes recurrence in islet grafts in spontaneously diabetic NOD
      mice.

PMID- 11985512
TI  - Immunological and pathological comparative analysis between experimental latent
      tuberculous infection and progressive pulmonary tuberculosis.
AB  - Mycobacterium tuberculosis produces latent infection or progressive disease.
      Indeed, latent infection is more common since it occurs in one-third of the
      world's population. We showed previously, using human material with latent
      tuberculosis, that mycobacterial DNA can be detected by in situ PCR in a variety
      of cell types in histologically-normal lung. We therefore sought to establish an
      experimental model in which this phenomenon could be studied in detail. We report
      here the establishment of such a model in C57Bl/6 x DBA/2 F1 hybrid mice by the
      intratracheal injection of low numbers of virulent mycobacteria (4000). Latent
      infection was characterized by low and stable bacillary counts without death of
      animals. Histological and immunological study showed granulomas and small patches
      of alveolitis, with high expression of tumour necrosis factor alpha (TNFalpha),
      inducible nitiric oxide synthase (iNOS), interleukin 2 (IL-2) and interferon
      gamma (IFNgamma). In contrast, the intratracheal instillation of high numbers of
      bacteria (1 x 106) produced progressive disease. These animals started to die
      after 2 months of infection, with very high bacillary loads, massive pneumonia,
      falling expression of TNF-alpha and iNOS, and a mixed Th1/Th2 cytokine pattern.
      In situ PCR to detect mycobacterial DNA revealed that the most common positive
      cells in latently-infected mice were alveolar and interstitial macrophages
      located in tuberculous lesions, but, as in latently-infected human lung, positive
      signals were also seen in bronchial epithelium, endothelial cells and fibroblasts
      from histologically-normal areas. Our results suggest that latent tuberculosis is
      induced and maintained by a type 1 cytokine pattern plus TNFalpha, and that
      mycobacteria persist intracellularly in lung tissue with and without histological
      evidence of a local immune response.

PMID- 11985513
TI  - Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas
      gingivalis in a mouse model.
AB  - T cell cytokine profiles and specific serum antibody levels in five groups of
      BALB/c mice immunized with saline alone, viable Fusobacterium nucleatum ATCC
      25586, viable Porphyromonas gingivalis ATCC 33277, F. nucleatum followed by P.
      gingivalis and P. gingivalis followed by F. nucleatum were determined. Splenic
      CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4,
      interferon (IFN)-gamma and IL-10 by dual colour flow cytometry and the levels of
      serum anti-F. nucleatum and anti-P. gingivalis antibodies determined by an ELISA.
      Both Th1 and Th2 responses were demonstrated by all groups, and while there were
      slightly lower percentages of cytokine positive T cells in mice injected with F.
      nucleatum alone compared with the other groups immunized with bacteria, F.
      nucleatum had no effect on the T cell production of cytokines induced by P.
      gingivalis in the two groups immunized with both organisms. However, the
      percentages of cytokine positive CD8 cells were generally significantly higher
      than those of the CD4 cells. Mice immunized with F. nucleatum alone had high
      levels of serum anti-F. nucleatum antibodies with very low levels of P.
      gingivalis antibodies, whereas mice injected with P. gingivalis alone produced
      anti-P. gingivalis antibodies predominantly. Although the levels of anti-F.
      nucleatum antibodies in mice injected with F. nucleatum followed by P. gingivalis
      were the same as in mice immunized with F. nucleatum alone, antibody levels to P.
      gingivalis were very low. In contrast, mice injected with P. gingivalis followed
      by F. nucleatum produced equal levels of both anti-P. gingivalis and anti-F.
      nucleatum antibodies, although at lower levels than the other three groups
      immunized with bacteria, respectively. Anti-Actinobacillus actinomycetemcomitans,
      Bacteroides forsythus and Prevotella intermedia serum antibody levels were also
      determined and found to be negligible. In conclusion, F. nucleatum immunization
      does not affect the splenic T cell cytokine response to P. gingivalis. However,
      F. nucleatum immunization prior to that of P. gingivalis almost completely
      inhibited the production of anti-P. gingivalis antibodies while P. gingivalis
      injection before F. nucleatum demonstrated a partial inhibitory effect by P.
      gingivalis on antibody production to F. nucleatum. The significance of these
      results with respect to human periodontal disease is difficult to determine.
      However, they may explain in part differing responses to P. gingivalis in
      different individuals who may or may not have had prior exposure to F. nucleatum.
      Finally, the results suggested that P. gingivalis and F. nucleatum do not induce
      the production of cross-reactive antibodies to other oral microorganisms.

PMID- 11985514
TI  - Up-regulation of MMP-8 and MMP-9 activity in the BALB/c mouse spinal cord
      correlates with the severity of experimental autoimmune encephalomyelitis.
AB  - Induction of EAE can be inhibited or repressed by administration of soluble
      metalloproteinase inhibitors. We studied the matrix metalloproteinase (MMP) and
      their tissue inhibitor (TIMP) expression pattern in experimental autoimmune
      encephalomyelitis (EAE) of the resistant Th2 prone BALB/c mouse, where the
      disease can be induced with ultrasound-emulsified antigen/adjuvant (son-ag), but
      not with conventional technique (syr-ag). We found highly elevated expression of
      MMP-8 (neutrophil collagenase) mRNA and protein in diseased son-ag challenged
      mice, colocalizing to neutrophil infiltrates found in brain and extensively in
      the spinal cord submeningeal space. MMP-8 expression has not been found
      previously in sensitive mouse strains. The infiltrates stained positive also for
      MMP-9 protein, and brain homogenates from corresponding mice showed MMP-9
      activity during overt disease (days 12-16 post-immunization). TIMP-1 gene
      expression could be detected in CNS samples from diseased son-ag challenged mice
      but not in syr-ag or control mice, and the TIMP-1 protein colocalized with GFAP
      staining. In contrast, in syr-ag mice both TIMP-2 and TIMP-3 gene expression in
      the spinal cords was elevated. The results show that sonication, but not
      extrusion, creates an adjuvant formula potent in activating the matrix
      metalloproteinase cascade similar to sensitive mouse strains, strongly
      implicating their role in EAE induction in this Th2 prone strain. The study
      provides the basis for establishment of MMP-specific therapy in this model.

PMID- 11985515
TI  - Induction of apoptosis and modulation of activation and effector function in T
      cells by immunosuppressive drugs.
AB  - Immunosuppressive drugs (ISD) are used for the prevention and treatment of graft
      rejection, graft-versus-host-disease (GVHD) and autoimmune disorders. The precise
      mechanisms by which ISD interfere with T cell activation and effector function or
      delete antigen-specific T cells are defined only partially. We analysed commonly
      used ISD such as dexamethasone (DEX), mycophenolic acid (MPA), FK506, cyclosporin
      A (CsA), rapamycin (RAP), methotrexate (MTX) and cyclophosphamide (CP) for
      apoptosis-induction and modulation of activation and effector function in human
      peripheral T cells, cytotoxic T cell lines (CTL) and Jurkat T cells. Of all drugs
      tested only CP and MTX prevented antigen-specific proliferation of T cells and
      decreased cytotoxicity of alloantigen specific CTL lines by direct induction of
      apoptosis. MTX and CP also slightly increased activation-induced cell death
      (AICD) and CD95-sensitivity. In contrast, all other drugs tested did not induce T
      cell apoptosis, increase CD95-sensitivity or AICD. CsA and FK506 even prevented
      AICD by down-modulation of CD95L. DEX, MPA, CsA, FK506 and RAP inhibited
      activation of naive T cells, but were not able to block proliferation of
      activated T cells nor decrease cytotoxic capacity of CTL lines. These results
      show that ISD can be classified according to their action on apoptosis-induction
      and inhibition of proliferation and would favour a rational combination therapy
      to delete existing reactive T cells and prevent further T cell activation.

PMID- 11985516
TI  - Caspase activation in the absence of mitochondrial changes in granulocyte
      apoptosis.
AB  - Eosinophils and neutrophils are two different types of granulocytes evolved from
      a common haematopoetic precursor in the bone marrow. Eosinophils are mainly
      involved in parasitic infection and allergic inflammation while neutrophils
      mainly participate in the defence against bacterial infections. Prolongation of
      granulocyte life span by inhibition of apoptosis may lead to tissue load of
      cells, and this has been detected in different inflammatory reactions. The
      molecular mechanisms and the potential role of the mitochondria in granulocyte
      apoptosis are poorly understood. In the present study we have characterized
      further the role of the mitochondria in granulocyte-apoptosis by studying the
      sequence of mitochondrial permeability transition (MPT) induction, loss of
      mitochondrial membrane potential (Deltapsim) and release of cytochrome c. This
      was made possible by applying tributyltin (TBT), a well-characterized apoptotic
      stimulus and MPT-inducer. We also studied potential differences in apoptosis
      susceptibility between eosinophils and neutrophils. Ten minutes of TBT-exposure
      resulted in a substantial caspase-3 activity in both eosinophils and neutrophils,
      followed by phosphatidylserine (PS)-exposure after 30-120 min. Interestingly,
      caspase-3 activity was not preceded by MPT-induction, loss of Deltapsim or by
      cytochrome c-release in either eosinophils or neutrophils. In conclusion, we have
      demonstrated an extremely rapid induction of caspase-3 activity and apoptosis in
      human blood granulocytes without prior mitochondrial changes, including loss of
      mitochondrial membrane potential and release of cytochrome c. Our results open
      the possibility for a mitochondrial-independent activation of caspase 3 and
      subsequent apoptosis in granulocytes.

PMID- 11985517
TI  - Effects of human placental lactogen on the expression of CD163 and CD14 on human
      monocytes in culture.
AB  - The effect of human placental lactogen (hPL), a member of the somatomammotrophin
      family, on the regulation of the scavenger receptor molecules CD14 and CD163 on
      human monocytes cultured for 48h was investigated. Cells were cultured in the
      presence or absence of the hormone and also in the presence or absence of IFN
      gamma and dexamethasone. Monocytes cultured in the presence of hPL showed a
      significant increase in the expression of CD14 in both males and females compared
      to background. When IFN-gamma and dexamethasone were added to the cultures, CD14
      expression was decreased and was not rescued by the presence of hPL. hPL alone
      had no effect on the expression of CD163 on cultured monocytes from either
      gender, although cells cultured in the presence of IFN-gamma and dexamethasone
      showed a profound increase in their expression of CD163. This expression was
      augmented further by the presence of hPL in the cultures over a 48-h period.
      These results support the hypothesis of a potential role of this hormone in the
      regulation of the innate immune response.

PMID- 11985518
TI  - Regulation of alpha1-proteinase inhibitor release by proinflammatory cytokines in
      human intestinal epithelial cells.
AB  - alpha1-Proteinase inhibitor (alpha1-PI) is the main serine proteinase inhibitor
      in human plasma. Apart from its synthesis in the liver, this anti-inflammatory
      protein is also synthesized by and excreted from human intestinal epithelial
      cells. Antiinflammatory actions of alpha1-PI are thought to be of relevance in
      the pathogenesis of inflammatory bowel disease. To investigate the role of
      macrophage-derived cytokines on alpha1-PI secretion from intestinal epithelial
      cells, we cultured Caco-2 cells until differentiation (14 days in culture) on
      permeable filter supports. Monolayers of differentiated Caco-2 cells were then co
      cultured with human peritoneal macrophages, grown on plastic in the basolateral
      chamber. Under these conditions, alpha1-PI secretion from Caco-2 cells was
      enhanced by 45%, probably by a direct action of macrophage-derived cytokines on
      Caco-2 cells. To extend this observation further, we treated differentiated Caco
      2 cells with macrophage-derived proinflammatory cytokines (IL-1beta, IL-8, TNF
      alpha), as well as with lymphocyte-derived cytokines IL-2, IL-6 and IFN-gamma. As
      early as after 24h treatment, IL-2 and IL-8 induced a significant and dose
      dependent increase of alpha-1-PI secretion into cell culture medium; this effect
      was completely reversed after immunoneutralization by the antibodies against IL-2
      and IL-8 alpha1-PI secretion was only slightly decreased after treatment with IFN
      gamma, while IL-1beta, IL-6 and TNF-alpha had no effect. alpha1-PI secretion
      correlated well with the expression of this protein in differentiated Caco-2
      cells after cytokine treatment, as confirmed by Western blot. Our data imply
      that, in vitro, alpha1-PI secretion in enterocyte-like Caco-2 cells is up
      regulated by IL-2 and IL-8. Our results suggest that both lymphocyte- and
      macrophage-derived cytokines regulate secretion of the anti-inflammatory protein
      alpha1-PI in intestinal epithelial cells.

PMID- 11985519
TI  - IFNgamma induces functional chemokine receptor expression in human mesangial
      cells.
AB  - Infiltration of leucocyte populations into sites of inflammation is a common
      feature in renal diseases. Glomerular mesangial cells are potent producers of a
      variety of chemokines, leading to specific attraction of distinct types of
      inflammatory leucocytes into the glomerulus, but so far there is limited
      knowledge about the responsiveness of mesangial cells to chemokines. We
      investigated the expression of chemokine receptors and the responsiveness of
      primary human mesangial cells (HMC) to the chemokines which they produce, namely
      monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-8. We found that
      mRNAs of the chemokine receptors CCR1, which has been shown before, CCR2 and
      CXCR2 were induced by T-helper cytokine interferon-gamma (IFNgamma). In IFNgamma
      stimulated cells, CCR2 and CXCR2 were detectable by flow cytometry. Following
      treatment with IFNgamma, HMC responded to MCP-1 and IL-8 with an increase of IL-6
      mRNA and protein expression, which was in part blocked by pertussis toxin.
      Moreover, chemokine stimulation of transfected HMC led to an activation of the
      immunoregulatory transcription factors NFkappaB and AP-1. Additionally, we found
      that MCP-1 enhanced the expression of its own mRNA in cells activated to express
      CCR2, suggesting autocrine feedback mechanisms in MCP-1 regulation. Finally,
      IFNgamma-activated cells migrated towards an MCP-1 gradient in a chemotaxis
      assay. These results strengthen the assumption that chemokines are not only
      involved in the recruitment of immune cells to inflamed tissues, but also seem to
      play a central role in the autocrine regulation of local tissue cells, leading to
      proceeding inflammation and possibly contributing to healing by mediating cell
      growth and migration.

PMID- 11985520
TI  - TCR usage and cytokine expression in peripheral blood and BAL T cells.
AB  - T cells are thought to play an important regulatory role in atopic asthma. We
      hypothesized that human blood and BAL T cell subsets bearing various TCR-Vbeta
      genes might show selective differences in their cytokine profile. Peripheral
      blood (PB) and bronchoalveolar lavage (BAL) T cells from seven atopic asthmatic
      and six non-atopic non-asthmatic subjects were stimulated with PMA and ionomycin
      in the presence of monensin and analysed for TCR-Vbeta expression and production
      of cytokines at the single cell level. The percentage of IFN-gamma- and IL-2
      producing BAL T cells was elevated compared with PB T cells from both the
      asthmatic subjects and the non-atopic, non-asthmatic controls. A small percentage
      of PB and BAL T cells produced IL-4 and IL-5, in asthmatic and normal subjects.
      In peripheral blood, the percentage of T cells expressing each cytokine was
      similar in the various TCR-Vbeta subsets and in total CD3+ T cells in all normal
      and six of seven asthmatic subjects. However, there was a substantial degree of
      heterogeneity in the cytokine profile of BAL TCR-Vbeta subsets compared with the
      total CD3+ T cells. This was more obvious in the asthmatic subjects with a
      reduction in the percentage of IFN-gamma- and IL-2-expressing T cells (five of
      seven asthmatic subjects) and an increase in the percentage of IL-4- and IL-5
      expressing T cells (two of seven asthmatic subjects). These data confirm previous
      findings of an elevated proportion of IFN-gamma- and IL-2-producing BAL T cells
      while only a small proportion of PB and BAL T cells produce IL-4 and IL-5.
      Moreover, subsets of BAL T cells, defined by their TCR-Vbeta usage, may differ in
      their cytokine profile compared with the total CD3+ T cells, implying that T
      cells expressing different Vbeta elements may play different roles in regulating
      the airway inflammation in asthma.

PMID- 11985521
TI  - The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the
      production of IL-10 by mononuclear cells in Graves' disease: the role of CD8+
      cells.
AB  - The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell
      activation in Graves' disease were investigated by analysing lymphocyte subsets
      in peripheral blood mononuclear cells (PBMC) and their production of soluble
      factors and cytokines such as IL-10 in patients with Graves' disease, Hashimoto's
      thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8
      depleted cells by magnetic separation columns, and cultured for 7 days with or
      without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was
      assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by
      flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased
      sCD23 levels and the number of CD23+ cells. The latter was further augmented by
      depletion of CD8+ cells. This combination of B cell stimulants increased
      production of IL-10 by PBMC from patients with Graves' disease. The CD40- and IL
      4-activated production of IL-10 was decreased by CD8+ cell depletion. In
      contrast, constitutive production of IL-10 was increased after CD8+ cell
      depletion in a group of patients with low basal secretion levels (<35 ng/ml). It
      was, however, decreased in a group with higher basal production levels, but such
      a relationship was not found in the normal control group. Thus, T cell-dependent
      B-cell activation via a CD40 pathway activates CD23+ cells, leading to over
      production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while
      CD8+ cells may suppress this activation to counteract the Th2 deviation in
      Graves' disease.

PMID- 11985522
TI  - Defining a T-cell epitope within HSP 65 in recurrent aphthous stomatitis.
AB  - The 65 kD heat shock protein (HSP) has been implicated in the aetiology of
      recurrent aphthous stomatitis (RAS). We have previously demonstrated that peptide
      91-105 derived from the sequence of mycobacterial 65 kD HSP stimulates
      specifically lymphocytes from patients with RAS. In this investigation, we show
      that both CD4+ and CD8+ T cells were significantly stimulated with mycobacterial
      peptide 91-105. In contrast, the human homologous peptide 116-130 stimulated only
      CD4+ T cells. Inhibition studies showed that CD4+ T cells were class II
      restricted, whereas CD8+ T cells were class I restricted. We then used truncated
      or substituted peptides, and demonstrated that residues 95-105 appear to be
      important, and residue 104(Arg) critical, in stimulating the T cells. Thus,
      peptide 95- 105 may constitute a T-cell proliferative epitope in RAS. We
      postulate that the high load of micro-organisms that colonize the oral mucosa may
      initiate an immune response by the microbial HSP 65-derived peptide 95-105,
      stimulating the numerous Langerhans cells in the oral mucosa to activate a cross
      reacting immune response to the homologous peptide 116-130 within the epithelial
      HSP 60, initiating the immunopathological changes that lead to RAS.

PMID- 11985523
TI  - Effect of CD14 promoter polymorphism and H. pylori infection and its clinical
      outcomes on circulating CD14.
AB  - CD14 is a pattern recognition receptor on the membranes of monocytes and
      macrophages for several microbial products, of which lipopolysaccharide (LPS) is
      the best known. A shed form of CD14 is present in serum. As the CD14 gene
      promoter polymorphism -159C/T and some bacterial infections may affect the sCD14
      levels, we compared the impact of both the CD14 promoter polymorphism and
      Helicobacter pylori infection on serum sCD14 levels in 201 dyspeptic patients
      (group 1) who had undergone gastroscopy, and 127 staff members (group 2) with no
      endoscopy. sCD14 was measured from the sera by a commercial enzyme immunoassay
      (EIA), and CD14 genotyping was carried out with PCR. Helicobacter pylori
      infection was detected by serology and/or culture or PCR. sCD14 levels were
      elevated in the subjects carrying the T allele (CT or TT genotype) in both groups
      when compared with subjects with the CC genotype. Overall, H. pylori-positive
      subjects tended to have higher sCD14 levels compared with H. pylori-negative
      subjects. In group 1 consisting of dyspeptic patients, those with gastric ulcer,
      gastric erosion or duodenal ulcer had significantly elevated levels of sCD14
      compared with the patients with normal endoscopic findings or macroscopic
      gastritis. The recent use of NSAIDs was also associated with enhanced sCD14.
      Thus, we were able to show several factors, one genetic and the other
      environmental (H. pylori infection and mucosal lesion), to have an impact on
      sCD14.

PMID- 11985524
TI  - High levels of inflammatory cytokines are associated with poor clinical response
      to steroid treatment and recurrent episodes of type 1 reactions in leprosy.
AB  - Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis
      factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy
      patients with type 1 reactions (T1R) before, during and after a standard 12-week
      course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy
      patients with untreated T1R produced significantly more TNF-alpha than leprosy
      patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients
      fell during treatment with steroids; however, TNF-alpha levels increased as the
      steroid dose was reduced. Median IL-10 levels increased throughout the steroid
      treatment period and were associated strongly with TNF-alpha levels. Patients
      with high cytokine levels had a poorer recovery of sensory or voluntary muscle
      nerve function, a higher risk of reactivation of symptoms during steroid
      treatment, and a higher risk of another episode of T1R within 2 months of
      completing the steroid regimen. Rapid and effective reversal of the inflammatory
      process in T1R is critical to prevent permanent nerve damage from T1R and
      monitoring cytokine levels during treatment may be useful.

PMID- 11985525
TI  - A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of
      influenza.
AB  - Influenza patients show a high incidence of T lymphocytopenia in the acute phase
      of the illness. Since CD8+ T cells play an important role in influenza virus
      infection, we investigated which subset of CD8+ T cells was involved in this
      lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied
      for lymphocyte count, surface marker, and intracellular IFN-gamma production in
      the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte
      counts in the acute phase were approximately three times less than in the
      recovery phase; however, the CD4/8 ratio was the same in both phases. The cell
      count reduction in the acute phase was attributed predominantly to the CD28+ CD8+
      subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO
      on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype,
      was reduced significantly in number in the acute phase compared with the recovery
      phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the
      acute phase, but the reduction was not statistically significant. Intracellular
      IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow
      cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was
      significantly less than in the recovery phase. These results indicated that the
      predominant reduction of peripheral CD8+ T cells in the acute phase of influenza
      was from naive-type lymphocytes, suggesting that these quantitative and
      qualitative changes of CD8+ T cells in influenza are important for understanding
      the immunological pathogenesis.

PMID- 11985526
TI  - Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in
      hepatitis C virus (HCV) infection.
AB  - Hepatitis C virus (HCV) infection has been found to be strikingly associated with
      autoimmune phenomena. The aim of the present study was to investigate the
      presence of various autoantibodies in patients with HCV infection. Anti
      neutrophil cytoplamic antibody (ANCA), anti-dihydrolipoamide dehydrogenase (anti
      E3), rheumatoid factor (RF), anti-dihydrolipoamide acetyltransferase (anti-E2),
      anti-SS-A/Ro (60 kD), anti-SS-A/Ro (52 kD), anti-SS-B/La, anti-topoisomerase II
      (anti-topo II), anti-cardiolipin (aCL), anti-dsDNA, anti-ssDNA, anti-nuclear
      antibodies (ANA), anti-proteinase 3 (anti-Pr3) and anti-myeloperoxidase (anti
      MPO) were determined in sera from 516 patients with HCV infection, 11 with
      primary biliary cirrhosis (PBC) and 44 healthy controls. Assays employed were
      indirect immunofluoresence, the particle latex agglutination test, enzyme-linked
      immunosorbent assay (ELISA) and immunoblotting. ANCA, anti-E3 antibody and RF
      were positive in 278/516 (55.6%), 276/516 (53.3%) and 288/516 (56%) patients with
      HCV infection, respectively. Positivity for ANA was present in 15.8%, anti-ssDNA
      in 15.6%, anti-dsDNA in 8.5%, aCL in 5%, anti-SS-B/La in 4.1%, anti-SS-A/Ro (60
      kD) in 3.9%, anti-E2 in 3.3% and anti-SSA/Ro (52 kD) in 1.2%, anti-MPO in 4.8%,
      anti-Topo II and anti-actinin in 0%. All sera with ANCA showed c-ANCA patterns
      and contained anti-PR3 specificity. HCV patients with ANCA showed a higher
      prevalence of skin involvement, anaemia, abnormal liver function and alpha
      Fetoprotein (alpha-FP). HCV patients with anti-E3 antibodies showed a higher
      prevalence of liver cirrhosis, arthritis, abnormal liver function and elevated
      alpha-FP levels. The prevalence of autoantibodies was not affected by treatment
      with interferon-alpha (IFN-alpha). In conclusion, autoantibodies are commonly
      found in patients with HCV infection. There is a high prevalence of anti-E3, ANCA
      and RF in these patients. Proteinase 3 and E3 are the major target antigens in
      HCV infection. HCV may be regarded as a possible causative factor in ANCA-related
      vasculitis.

PMID- 11985527
TI  - Peripheral B-cell CD5 expansion and CD81 overexpression and their association
      with disease severity and autoimmune markers in chronic hepatitis C virus
      infection.
AB  - Hepatitis C virus (HCV) infection is associated with immune-mediated
      abnormalities and B-cell lymphoproliferation evolving to an overt lymphoma.
      Recently, CD81 was identified as an HCV receptor on B-lymphocytes, providing a
      mechanism by which B cells are infected and activated by the virus. In addition,
      expansion of CD5+ B lymphocytes was described to be associated with various non
      HCV related autoimmune disorders. Therefore, we studied the possible role of
      peripheral B cells CD81 and CD5 over-expression in the development of HCV-related
      autoimmunity and their association with disease severity in chronic HCV
      infection. Peripheral B cells CD5 expression and mean fluorescence intensity
      (MFI) of CD81 were determined in 30 HCV-infected patients, 30 healthy controls
      and 15 patients with hepatitis B virus infection using fluorescence-activated
      cell scan (FACS). We have also investigated the association between peripheral
      CD5 and CD81 B-cell over-expression and markers of autoimmunity and disease
      severity in patients chronically infected by HCV. CD5+ B-cells were increased in
      chronic HCV infection (23.2 +/- 7.2%) compared with those of healthy controls (15
      +/- 5.5%) (P < 0.0001) and chronic HBV infection (19 +/- 3.7%) (P = 0.08). CD81
      MFI was significantly higher in HCV-infected compared to HBV-infected patients
      and healthy controls. Both increased CD81 MFI and CD5+ B-cell expansion were
      associated with the production of rheumatoid factor and mixed cryoglobulins and
      positively correlated with HCV viral load and histological activity index. The
      overexpression of CD81 and the expansion of CD5+ peripheral B-cells in HCV
      infected patients may possibly play a role in the development of HCV-associated
      autoimmunity and lymphoproliferation.

PMID- 11985528
TI  - Predictors of HIV-specific lymphocyte proliferative immune responses induced by
      therapeutic vaccination.
AB  - We treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine
      (REMUNE, HIV-1 Immunogen) in an open label study. We then determined whether
      baseline parameters, such as CD4 cell count, viral load and IgG levels, were
      predictive of the magnitude of the HIV-specific lymphocyte proliferative
      responses (LPRs). We demonstrate herein that there is a significant enhancement
      from baseline for both HIV and p24 antigen-stimulated LPRs after immunization.
      Using a responder definition of a stimulation index of >5 on at least two post
      immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38
      (71%) responded to native p24 antigen. Viral load and total IgG were negatively
      correlated, while CD4 cell counts were positively associated with the magnitude
      of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best
      predictor of HIV antigen LPR post-immunization.

PMID- 11985529
TI  - Highly active antiretroviral therapy restores in vitro mitogen and antigen
      specific T-lymphocyte responses in HIV-1 perinatally infected children despite
      virological failure.
AB  - To analyse the effect of highly active antiretroviral therapy (HAART) on T
      lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC
      immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA
      levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART.
      Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+,
      CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses
      to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen)
      and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline
      and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children
      were studied as controls. A gain in body weight, no worsening of the disease and
      no recurrence of opportunistic infections were observed. At baseline, the
      majority of the children had low responses to mitogens, and all of them had a
      defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations
      below the mean result for controls). During HAART, a significant increase in the
      response to mitogens and antigens was observed in all the patients. The T
      lymphocyte response was restored more consistently against antigens to which the
      immune system is constantly exposed (Candida albicans, baseline versus 12 months:
      P < 0.001) compared with a low-exposure antigen (tetanus toxoid, baseline versus
      12 months: P < 0.01). HAART restores in vitro T-lymphocyte responses even in the
      absence of a significant viral load decrease and despite any significant increase
      in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved
      in the overall immune recovery under HAART.

PMID- 11985530
TI  - Transforming growth factor-beta expression in human retinal pigment epithelial
      cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis
      of retinochoroiditis.
AB  - Retinochoroiditis caused by Toxoplasma gondii infection results in inflammation
      and necrosis of the retina. We have used human retinal pigment epithelial
      cultures (HRPE) as an in vitro model to investigate the role of TGF-beta in T.
      gondii-induced retinochoroiditis. RT-PCR analyses showed enhanced steady state
      levels of TGF-beta1 and TGF-beta2 mRNA in T. gondii-infected HRPE. Uninfected
      HRPE secrete TGF-beta1 in a latent form while 10-30% of the secreted TGF-beta2
      was in the active form. T. gondii infection induced a significant increase (P <
      0.01) in total TGF-beta1 and TGF-beta2 secretion by HRPE. In addition, soluble
      extracts of T. gondii (ST) stimulated secretion of both TGF-beta1 and TGF-beta2
      significantly (P < 0.01). Interestingly, T. gondii infection as well as ST of the
      parasites completely inhibited secretion of the active form of TGF-beta2. Studies
      evaluating the effect of TGF-beta on T. gondii replication in HRPE revealed that
      TGF-beta enhanced parasite replication. The interactions between host retinal
      cells and T. gondii may play an active role in the pathogenesis of
      retinochoroiditis.

PMID- 11985531
TI  - Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells.
AB  - Myeloid (CD11c+) dendritic cells (DC) are present in cerebrospinal fluid (CSF),
      as well as in the meninges and choroid plexus. Functional studies of these DC are
      hindered or impossible. To obviate this problem, we investigated the effects of
      CSF supernatants from patients with non-inflammatory neurological diseases
      (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme
      meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy
      donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as
      reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86
      expression. The maturation effect of MS CSF and LM CSF could be blocked by anti
      TNF-alpha MoAb or recombinant human IL-10. moDC cultured with BM CSF either
      remained immature or turned into CD14+ macrophage-like cells and were relatively
      inefficient at inducing T cell responses in vitro. In contrast, moDC cultured
      with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN
      gamma, a cytokine that augments IL-12 production by moDC and hence should confer
      an ability to induce a Th1 response. However, BM CSF also contained high levels
      of IL-10, which could antagonize the effects of IFN-gamma on moDC. moDC cultured
      with MS CSF induced a higher production of IFN-gamma from T cells compared to
      moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the
      CSF may influence the phenotype and functions of meningeal, choroid plexus and
      CSF DC which, in turn, may have an impact on the character of intrathecal T cell
      responses.

PMID- 11985532
TI  - Down-regulated donor-specific T-cell reactivity during successful tapering of
      immunosuppression after kidney transplantation.
AB  - Stable cadaveric renal transplant patients were routinely converted from
      cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1
      year after transplantation to reduce the side effects of long-term
      immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered
      to 50% at 2 years after transplantation. We questioned whether a reduction of
      immunosuppressive treatment results in a rise of donor-specific T-cell
      reactivity. Before transplantation (no immunosuppression), 1 year (high dose
      immunosuppression) and 2 years (low dose immunosuppression) after
      transplantation, the T-cell reactivity of peripheral blood mononuclear cells
      (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte
      cultures (MLC) and against tetanus toxoid (TET) to test the general immune
      response. We also measured the frequency of donor and third-party reactive helper
      (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution
      assay. Donor-specific responses, calculated by relative responses (RR =
      donor/third-party reactivity), were determined. Comparing responses after
      transplantation during high dose immunosuppression with responses before
      transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0.04),
      HTLp-RR (P = 0.04) and CTLp-RR (P = 0.09) decreased, while the TET-reactivity did
      not change. Comparing the responses during low dose with high dose
      immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp
      RR and CTLp-RR, although TET-reactivity increased considerably (P = 0.0005). We
      observed a reduction in donor-specific T-cell reactivity in stable patients after
      renal transplantation during in vivo high dose immunosuppression. Tapering of the
      immunosuppressive load had no rebound effect on the donor-specific reactivity,
      while it allowed recovery of the response to nominal antigens.

PMID- 11985533
TI  - Central mechanisms underlying short- and long-term regulation of the
      cardiovascular system.
AB  - 1. Sympathetic vasomotor nerves play a major role in determining the level of
      arterial blood pressure and the distribution of cardiac output. The present
      review will discuss briefly the central regulatory mechanisms that control the
      sympathetic outflow to the cardiovascular system in the short and long term. 2.
      In the short term, the sympathetic vasomotor outflow is regulated by: (i)
      homeostatic feedback mechanisms, such as the baroreceptor or chemoreceptor
      reflexes; or (ii) feed-forward mechanisms that evoke cardiovascular changes as
      part of more complex behavioural responses. 3. The essential central pathways
      that subserve the baroreceptor reflex and, to a lesser extent, other
      cardiovascular reflexes, have been identified by studies in both anaesthetized
      and conscious animals. A critical component of these pathways is a group of
      neurons in the rostral ventrolateral medulla that project directly to the spinal
      sympathetic outflow and that receive inputs from both peripheral receptors and
      higher centres in the brain. 4. Much less is known about the central pathways
      subserving feed-forward or 'central command' responses, such as the
      cardiovascular changes that occur during exercise or that are evoked by a
      threatening or alerting stimulus. However, recent evidence indicates that the
      dorsomedial hypothalamic nucleus is a critical component of the pathways
      mediating the cardiovascular response to an acute alerting stimulus. 5. Long-term
      sustained changes in sympathetic vasomotor activity occur under both
      physiological conditions (e.g. a change in salt intake) and pathophysiological
      conditions (e.g. heart failure). There is evidence that the paraventricular
      nucleus in the hypothalamus is a critical component of the pathways mediating
      these changes. 6. Understanding the central mechanisms involved in the long-term
      regulation of sympathetic activity and blood pressure is a major challenge for
      the future. As a working hypothesis, a model is presented of the postulated
      central mechanisms that result in sustained changes in sympathetic vasomotor
      activity that are evoked by different types of chronic stimulation.

PMID- 11985534
TI  - Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar
      fatty rats.
AB  - 1. The effects of combined treatment with pioglitazone.HCl and metformin on
      diabetes and obesity were investigated in Wistar fatty rats, which are
      hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total
      ketone bodies than lean rats. 2. Plasma glucose was significantly decreased when
      pioglitazone.HCl or metformin was administered alone and combined treatment
      accentuated this decrease. The administration of pioglitazone.HCl, but not
      metformin, also decreased plasma levels of triglyceride and total ketone bodies.
      3. The glycogen content of skeletal muscle was not increased by pioglitazone.HCl
      or metformin alone, but was increased by combined treatment (P=0.003, ANOVA). 4.
      Pioglitazone.HCl produced increased food intake and bodyweight in hyperphagic
      Wistar fatty rats; however, concurrent administration of metformin significantly
      ameliorated these pioglitazone.HCl-induced increases. 5. These results indicate
      that combined treatment with pioglitazone.HCl and metformin induces a marked
      hypoglycaemic effect accompanied by a reduction in plasma levels of total ketone
      bodies and prevention of excessive bodyweight gain in Wistar fatty rats. These
      favourable effects suggest that the combination would be beneficial in treating
      patients with type 2 diabetes.

PMID- 11985535
TI  - Nitric oxide in mesenteric vascular reactivity: a comparison between rats with
      normotension and hypertension.
AB  - 1. Nitric oxide (NO) plays an important role in various physiological functions.
      The continuous formation of endogenous NO from endothelial cells maintains a
      vasodilator tone and regulates blood flow and pressure. However, the role of NO
      in hypertension remains controversial. 2. In the present study, we used an in
      situ mesenteric perfusion system. The primary objectives of the study were to
      examine whether or not mesenteric vasoreactivity is changed by alterations in
      perfusion pressure and to assess the role of NO in changes of vascular reactivity
      in hypertension. 3. Spontaneously hypertensive rats (SHR; 12-15 weeks of age) and
      age-matched normotensive Wistar-Kyoto (WKY) rats were used as the experimental
      and control groups, respectively. Endothelium-dependent and -independent
      vasodilation was detected by acetylcholine (ACh) or NO donors (sodium
      nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP)). Dose-dependent
      reactivity to these agents (10(-6) to 10(-4) mol/L) was detected by bolus intra
      arterial injections of 10 microL of the test agents at 5 min intervals. Dose
      dependent responses to vasoconstrictor drugs, such as noradrenaline (NA) and
      phenylephrine (PE; 10(-6) to 10(-4) mol/L) were also observed. The NO synthase
      inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) was given to
      examine the contribution of NO to the vasoreactivity of the mesenteric bed. 4.
      Acetylcholine, SNP and SNAP produced dose-dependent vasodilation in both WKY rats
      and SHR. The magnitude of the vasodilation was significantly greater in SHR than
      in WKY rats. It was also greater at high than low flow rates in SHR. The increase
      in mesenteric perfusion pressure following L-NAME was significantly higher in SHR
      than in WKY rats. However, there were no differences in responses to L-NAME
      between low and high flow rates in SHR. Endothelium-independent vasoconstriction
      (NA and PE) was dose dependent in both SHR and WKY rats. The magnitude of the
      endothelium-independent vasoconstriction was greater in SHR than in WKY rats. 5.
      The results suggest that endothelium-dependent or -independent mesenteric
      vasoconstriction and vasodilation is enhanced in SHR compared with WKY rats,
      supporting the concept of enhancement of NO function in the hypertensive state.
      Flow-induced shear stress is also a key factor in the regulation of peripheral
      resistance depending on NO formation in hypertension.

PMID- 11985536
TI  - Effect of alpha-lipoic acid on lipid peroxidation and anti-oxidant enzyme
      activities in diabetic rats.
AB  - 1. Oxidative damage has been suggested to be a contributory factor in the
      development and complications of diabetes. Recently, alpha-lipoic acid (ALA) has
      gained considerable interest as an anti-oxidant. Various studies have indicated
      the anti- oxidant effects of ALA and its reduced form dihydrolipoic acid.
      Therefore, it appears that these compounds have important therapeutic potential
      in conditions where oxidative stress is involved. The aim of the present study
      was to investigate the effect of ALA supplementation on lipid peroxidation and
      anti-oxidant enzyme activities in various tissues in diabetic rats. 2. Male
      Wistar rats were divided into three groups. Diabetes was induced by
      streptozotocin (STZ) injection in the two groups of rats to be supplemented and
      not to be supplemented with ALA. Another group of rats, which received saline
      injection, formed the control group. After 5 weeks of diabetes, rats were killed.
      In order to assess the redox status of various organs in the diabetic and control
      rats, thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH)
      levels, as well as superoxide dismutase (SOD), glutathione peroxidase (G-Px) and
      glutathione reductase (G-Red) activities were determined in the liver, pancreas
      and kidney. 3. In both diabetic groups, TBARS levels and SOD activity were
      increased in the liver and pancreas, G-Px and G-Red activities were increased in
      the kidney and GSH levels were decreased in all organs compared with controls. In
      the ALA- supplemented group, TBARS levels were decreased, GSH levels were
      increased in the liver and pancreas, SOD activity was decreased in the liver, G
      Px activity remained unchanged in all tissues and G-Red activity was increased in
      the pancreas compared with the diabetic group that did not receive ALA
      supplementation. 4. In conclusion, ALA supplementation has disparate effects on
      the redox status of different organs. These data are not sufficient for
      confirmation the beneficial effects of ALA supplementation on the redox status of
      various organs in diabetic rats.

PMID- 11985537
TI  - Neutrophil migration during liver cirrhosis in rabbits.
AB  - 1. The aim of the present study was to investigate neutrophil chemotaxis during
      the induction of liver cirrhosis in rabbits. 2. Liver cirrhosis was induced in
      male New Zealand white rabbits. The study consisted of three experimental groups:
      (i) group A (n=16) served as the control and received only normal chow and all
      rabbits in this group were killed at 16 weeks; (ii) group B rabbits (n=8) were
      killed immediately after the chemotaxis assay, which was performed 24 h after
      CCl4 administration, at weeks 2, 4, 6 and 8; and (iii) in group C rabbits (n=19),
      the chemotaxis assay was performed every second week on the day before CCl4
      administration for 16 weeks and all animals in this group were killed at 16
      weeks. 3. Four of six rabbits in group B had liver cirrhosis at week 8. In group
      C, liver cirrhosis occurred in seven of eight animals. All rabbits with liver
      cirrhosis had an inflammatory infiltrate of neutrophils. In group B, there was a
      significant increase in polymorphonuclear cells and neutrophil chemotaxis and a
      significant reduction in mononuclear leucocytes at week 8. The rabbits in group C
      showed a significant increase in total leucocyte and polymorphonuclear numbers at
      week 10. A significant increase in neutrophil chemotaxis was also observed from
      week 2 through to week 6. 4. The presence of neutrophils in the liver of all
      rabbits with cirrhosis, associated with an increase in polymorphonuclear cell
      chemotaxis during this process, supports the view that this cell type has an
      important role in the development of toxic liver damage.

PMID- 11985538
TI  - Modulation Of [35S]-tert-butylbicyclophosphorothionate binding by somatostatin in
      rat hypothalamus.
AB  - 1. The present study was designed to assess the effect of the tetradecapeptide
      somatostatin on the GABA(A) receptor complex in the rat hypothalamus. 2. GABA(A)
      receptors were labelled with [35S]-tert-butylbicyclophosphorothionate (TBPS),
      which binds in or near the chloride channel, and binding as assessed by in vitro
      quantitative autoradiography using a computer-assisted image analysis system. 3.
      Somatostatin inhibited the binding of [35S]-TBPS to the convulsant site of the
      hypothalamic GABA(A) receptor complex of rat slide-mounted hypothalamic
      structures in a concentration-dependent manner with an affinity in the micromolar
      range (10(-6) to 3 x 10(-6) mol/L). Somatostatin appeared to mimic the effects of
      the neurosteroid 5alpha-pregnane-3alpha ol-one (5alpha3alphaP), GABA and
      picrotoxin on [35S]-TBPS binding in the rat hypothalamus in all structures
      examined. Furthermore, GABA or muscimol (a GABA(A) receptor agonist), when added
      to the incubation medium, enhanced the capacity of somatostatin to inhibit [35S]
      TBPS binding, with an IC50 of 10(-7) mol/L. However, incubation with bicuculline
      (a GABA(A) receptor antagonist) led to the abolition of the inhibitory effect of
      somatostatin on [35S]-TBPS specific binding in rat hypothalamus. 4. The present
      results demonstrate the presence of a modulatory effect of somatostatin on the
      GABA(A) receptor complex in rat hypothalamic structures. Furthermore, the data
      suggest that somatostatin allosterically modifies [35S]-TBPS binding through a
      mechanism similar to that of GABA. Taken together, these results provide evidence
      for the presence of somatostatin- GABA interactions in rat hypothalamus.

PMID- 11985539
TI  - Altered expression of vascular natriuretic peptide receptors in experimental
      hypertensive rats.
AB  - 1. The aim of the present study was to determine whether the regulation of
      vascular natriuretic peptide receptors (NPR) is related to the local renin
      angiotensin system (RAS). 2. Male Sprague-Dawley rats were made two-kidney, one
      clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive to activate
      and inhibit the RAS, respectively. Another model of hypertension was induced by
      treatment with an inhibitor of nitric oxide synthesis, namely NG-nitro-L-arginine
      methyl ester (L-NAME). 3. The mRNA expression of NPR-A, NPR-C, angiotensin-
      converting enzyme (ACE) and angiotensin AT1 receptors was determined in the
      thoracic aorta by semiquantitative reverse transcription-polymerase chain
      reaction. The particulate guanylyl cyclase activity stimulated by atrial
      natriuretic peptide (ANP) was also determined in the membrane fraction of the
      thoracic aorta. 4. The plasma concentrations of ANP were increased significantly
      in the three models of hypertension. Plasma renin activity was increased in 2K1C
      hypertension, decreased in DOCA-salt hypertension and not significantly altered
      in L-NAME hypertension. 5. The mRNA expression of NPR-A and NPR-C was decreased,
      whereas that of ACE and AT1 receptors was increased in 2K1C and L-NAME
      hypertension. The mRNA expression of NPR-A and NPR-C was increased, whereas that
      of ACE and AT1 receptors was decreased in DOCA-salt hypertension. 6. The
      particulate guanylyl cyclase activity was decreased in 2K1C and L-NAME
      hypertension and increased in DOCA-salt hypertension. 7. The vascular expression
      of NPR may be reciprocally regulated by local RAS activity.

PMID- 11985541
TI  - Oxidative stress and potassium channel function.
AB  - 1. Modulation of K+ channel activities by cellular oxidative stress has emerged
      as a significant determinant of vasomotor function in multiple disease states. 2.
      Evidence from in vitro and in vivo studies suggest that superoxide (O2-) and
      hydrogen peroxide (H2O2) enhance BKCa channel activity in rat and cat cerebral
      arterioles; however, activity is decreased by peroxynitrite (ONOO-) in rat
      cerebral arteries. The mechanisms of changes in BKCa channel properties are not
      fully understood and may involve oxidation of cysteine residues that are located
      in the cell membranes. 3. Studies further suggest that O2- increases KATP channel
      activity in guinea-pig cardiac myocytes, but decreases opening in cerebral
      vasculature. Both H2O2 and ONOO- enhance KATP channel activity in the myocardium
      and in coronary, renal, mesenteric and cerebral vascular beds. Alteration of KATP
      channels by free radicals may be due to oxidation of SH groups or changes in the
      cytosolic concentration of ATP. 4. It does appear that O2- produced by either
      reaction of xanthine and xanthine oxidase or elevated levels of glucose reduces
      Kv channel activity and the impairments can be partially restored by free radical
      scavengers, superoxide dismutase and catalase. 5. Thus, redox modulation of
      potassium channel activity is an important mechanism regulating cell vascular
      smooth muscle membrane potential.

PMID- 11985542
TI  - Functional roles of KATP channels in vascular smooth muscle.
AB  - 1. ATP-sensitive potassium channels (K(ATP)) are present in vascular smooth
      muscle cells and play important roles in the vascular responses to a variety of
      pharmacological and endogenous vasodilators. 2. The K(ATP) channels are composed
      of four inwardly rectifying K+ channel subunits and four regulatory sulphonylurea
      receptors. The K(ATP) channels are inhibited by intracellular ATP and by
      sulphonylurea agents. 3. Pharmacological vasodilators such as cromakalim,
      pinacidil and diazoxide directly activate K(ATP) channels. The associated
      membrane hyperpolarization closes voltage-dependent Ca2+ channels, which leads to
      a reduction in intracellular Ca2+ and vasodilation. 4. Endogenous vasodilators
      such as calcitonin gene-related peptide, vasoactive intestinal polypeptide,
      prostacylin and adenosine activate K(ATP) by stimulating the formation of cAMP
      and increasing the activity of protein kinase A. Part of the mechanism of
      contraction of endogenous vasoconstrictors is due to inhibition of K(ATP)
      channels. 5. The K(ATP) channels appear to be tonically active in some vascular
      beds and contribute to the physiological regulation of vascular tone and blood
      flow. These channels also are activated under pathophysiological conditions, such
      as hypoxia, ischaemia, acidosis and septic shock, and, in these disease states,
      may play an important role in the regulation of tissue perfusion.

PMID- 11985543
TI  - Molecular diversity of vascular potassium channel isoforms.
AB  - 1. One essential role for potassium channels in vascular smooth muscle is to
      buffer cell excitation and counteract vasoconstrictive influences. Several
      molecular mechanisms regulate potassium channel function. The interaction of
      these mechanisms may be one method for fine-tuning potassium channel activity in
      response to various physiological and pathological challenges. 2. The most
      prevalent K+ channels in vascular smooth muscle are large-conductance calcium-
      and voltage-sensitive channels (maxi-K channels) and voltage-gated channels (Kv
      channels). Both channel types are complex molecular structures consisting of a
      pore-forming alpha-subunit and an ancillary beta-subunit. The maxi-K and Kv
      channel alpha-subunits assemble as tetramers and have S4 transmembrane domains
      that represent the putative voltage sensor. While most vascular smooth muscle
      cells identified to date contain both maxi-K and Kv channels, the expression of
      individual alpha-subunit isoforms and beta-subunit association occurs in a tissue
      specific manner, thereby providing functional specificity. 3. The maxi-K channel
      alpha-subunit derives its molecular diversity by alternative splicing of a single
      gene transcript to yield multiple isoforms that differ in their sensitivity to
      intracellular Ca2+ and voltage, cell surface expression and post- translational
      modification. The ability of this channel to assemble as a homo- or
      heterotetramer allows for fine-tuning control to intracellular regulators.
      Another level of diversity for this channel is in its association with accessory
      beta-subunits. Multiple beta-subunits have been identified that can arise either
      from separate genes or alternative splicing of a beta-subunit gene. The maxi-K
      channel beta-subunits modulate the channel's Ca2+ and voltage sensitivity and
      kinetic and pharmacological properties. 4. The Kv channel alpha-subunit derives
      its diverse nature by the expression of several genes. Similar to the maxi-K
      channel, this channel has been shown to assemble as a homo- and heterotetramer,
      which can significantly change the Kv current phenotype in a given cell type.
      Association with a number of the ancillary beta-subunits affects Kv channel
      function in several ways. Beta-subunits can induce inactivating properties and
      act as chaperones, thereby regulating channel cell-surface expression and current
      kinetics.

PMID- 11985544
TI  - Role of augmented expression of intermediate-conductance Ca2+-activated K+
      channels in postischaemic heart.
AB  - 1. The rat intermediate conductance calcium-activated potassium channel (ImK) was
      cloned from a cDNA library of vascular smooth muscle cells (VSM) in rat pulmonary
      artery. The ImK distributes in a variety of tissue, including VSM, endothelial
      cells, leucocytes and fibroblasts. The ImK has a tyrosine phosphorylation
      consensus site in the proximal portion of the C-terminus and motifs exist for the
      DNA-binding protein AP-1 in the promoter, suggesting this channel is upregulated
      and active in cell cycle functions. The aim of the present study was to examine
      the role of ImK in postischaemic cardiovascular remodelling in relation to the
      angiotensin AT1 receptor-mediated AP-1 signalling pathway. 2. Rats underwent left
      coronary artery ligation for periods between 1 day and 3 weeks. The temporal
      profile of expression of ImK mRNA was analysed by RNase protection assay. To test
      the effect of AT1 receptor blockade, candesartan (3 mg/kg per day) was
      administered via an osmotic mini-pump implanted in the intraperitoneal space 3
      days prior to coronary occlusion. 3. ImK expression in postischaemic hearts
      showed a significant increase with two distinct peaks; the first peak at day 3
      (2.7-fold compared with control levels; P < 0.001) and the second after 2 weeks
      (1.5-fold; P < 0.01). Reperfusion following 30 min of ischaemia markedly
      accelerated and augmented the first peak at days 1-3 (4.8-fold), but completely
      abolished the second peak after 1-2 weeks (0.8-fold). In situ hybridization of
      ImK mRNA and immunostaining of ImK protein with specific antibody revealed that
      this was not only the result of the increase in ImK expression in vascular cells,
      but also related to infiltration of mononuclear leucocytes and fibroblasts into
      the ischaemic region. Candesartan inhibited cardiac hypertrophy and perivascular
      fibrosis of coronary arterioles in the non-ischaemic region. Candesartan also
      abrogated both peaks in ImK expression. 4. These findings indicate that both the
      inflammatory reaction and the postischaemic cardiovascular remodelling promote
      increased expression of ImK in postischaemic hearts via the AT1 receptor-mediated
      AP-1 signalling pathway.

PMID- 11985545
TI  - Potassium channels underlying the resting potential of pulmonary artery smooth
      muscle cells.
AB  - 1. The molecular identity of the K channels giving rise to the negative membrane
      potential of pulmonary artery smooth muscle cells has yet to be determined. 2. To
      date, most studies have focused on voltage-gated, delayed rectifier channels and
      their roles in mediating hypoxia-induced membrane depolarization. There is,
      however, strong evidence that an outwardly rectifying K+ conductance distinct
      from the classical delayed rectifier is involved. 3. Growing evidence that TASK
      like channels can sense hypoxia and are present in pulmonary artery smooth muscle
      cells suggests that they may be responsible for the resting K+ conductance and
      resting potential. 4. The present review considers the evidence that particular K
      channels maintain the resting membrane potential of pulmonary artery smooth
      muscle cells and mediate the depolarizing response to hypoxia.

PMID- 11985546
TI  - The adenine nucleotide translocator: regulation and function during myocardial
      development and hypertrophy.
AB  - 1. The present review focuses on the adenine nucleotide translocator (ANT), which
      facilitates exchange of cytosolic ADP for mitochondrial ATP. This protein serves
      a central role in regulating cellular oxidative capacity. 2. The ANT, a nuclear
      encoded mitochondrial protein, is developmentally regulated and, thus,
      accumulates within the mitochondrial membrane during maturation. 3. Accumulation
      of ANT parallels changes in kinetics of myocardial respiration determined from
      31P magnetic resonance spectroscopy studies. 4. Thyroid hormone modulates
      developmental transitions in ANT content, as well as respiratory control
      patterns. These transitions are linked to quantitative ANT changes, not to
      alterations in functionality at individual exchanger sites. 5. Developmental
      programming for ANT and parallel alterations in oxidative phosphorylation
      kinetics are relevant to the heart, which exhibits remodelling in response to
      pathological processes. Maladaptive hearts exhibiting ANT deficits demonstrate
      ADP-dependent respiratory kinetics similar to the newborn heart. Thus, ANT
      deficits and alterations in mitochondrial respiratory function may contribute to
      the pathogenesis of myocardial remodelling and heart failure.

PMID- 11985547
TI  - Transcriptional activation of energy metabolic switches in the developing and
      hypertrophied heart.
AB  - 1. The present review focuses on the gene regulatory mechanisms involved in the
      control of cardiac mitochondrial energy production in the developing heart and
      following the onset of pathological cardiac hypertrophy. Particular emphasis has
      been given to the mitochondrial fatty acid oxidation (FAO) pathway and its
      control by members of the nuclear receptor transcription factor superfamily. 2.
      During perinatal cardiac development, the heart undergoes a switch in energy
      substrate preference from glucose in the fetal period to fatty acids following
      birth. This energy metabolic switch is paralleled by changes in the expression of
      the enzymes and protein involved in the respective pathways. 3. The postnatal
      activation of the mitochondrial energy production pathway involves the induced
      expression of nuclear genes encoding FAO enzymes, as well as other proteins
      important in mitochondrial energy transduction/production pathways. Recent
      evidence indicates that this postnatal gene regulatory effect involves the
      actions of the nuclear receptor peroxisome proliferator-activated receptor alpha
      (PPARalpha) and its coactivator the PPARgamma coactivator 1 (PGC-1). 4. The PGC-1
      not only activates PPARalpha to induce FAO pathway enzymes in the postnatal
      heart, but it also plays a pivotal role in the control of cardiac mitochondrial
      number and function. Thus, PGC-1 plays a master regulatory role in the high
      capacity mitochondrial energy production system in the adult mammalian heart. 5.
      During the development of pathological forms of cardiac hypertrophy, such as that
      due to pressure overload, the myocardial energy substrate preference shifts back
      towards the fetal pattern, with a corresponding reduction in the expression of
      FAO enzyme genes. This metabolic shift is due to the deactivation of the
      PPARalpha/PGC-1 complex. 6. The deactivation of PPARalpha and PGC-1 during the
      development of cardiac hypertrophy involves regulation at several levels,
      including a reduction in the expression of these genes, as well as post
      translational effects due to the mitogen-activated protein kinase pathway. Future
      studies aim at defining whether this transcriptional 'switch' and its effects on
      myocardial metabolism are adaptive or maladaptive in the hypertrophied heart.

PMID- 11985548
TI  - Mitochondrial proteins in hypertrophy and atrophy: a transcript analysis in rat
      heart.
AB  - 1. Metabolic processes are acutely and chronically regulated in response to
      changes in the workload of the heart. Acute changes in cardiac work result in
      activation and inactivation of existing enzymes and in altered fluxes through
      existing metabolic pathways. Sustained or chronic changes in cardiac work result
      in both trophic and transcriptional alterations. 2. The metabolic consequences of
      a sustained increase or decrease in the workload of the heart are surprisingly
      uniform and consist of a switch from the predominant oxidation of fatty acids to
      oxidation of glucose. 3. This switch is reflected in the changes of the
      transcript levels of three key regulators of mitochondrial function: pyruvate
      dehydrogenase kinase 4 (PDK4), which phosphorylates and inactivates the pyruvate
      dehydrogenase complex, malonyl-CoA decarboxylase (MCD), which regulates malonyl
      CoA levels and, therefore, rates of beta-oxidation of long-chain fatty acids, and
      uncoupling protein 3 (UCP-3), which uncouples the oxidative phosphorylation of
      ADP. 4. The transcript levels of all three proteins are downregulated in
      hypertrophy as well as in atrophy of rat heart. All three transcripts are
      transcriptionally regulated by the nuclear receptor peroxisome proliferator
      activated receptor alpha (PPARalpha). 5. Diminished expression of PPARalpha and
      PPARalpha-regulated genes constitutes an adaptive mechanism in response to
      altered workload, because reactivation of PPARalpha in hypertrophied heart
      results in severe contractile dysfunction.

PMID- 11985549
TI  - Myocardial energetics in cardiac hypertrophy.
AB  - 1. This review is presented with the intent of illustrating the representative
      studies of functional and myocardial energetic consequences of hearts with
      postinfarction left ventricular (LV) remodelling or with concentric hypertrophy
      and diastolic LV dysfunction in porcine models. 2. Both eccentric and concentric
      cardiac hypertrophy are associated with the abnormal myocardial energetics that
      are most severe in hearts with congestive heart failure (CHF). Presently, these
      abnormalities cannot be satisfactorily explained to be the cause(s) of the
      dysfunction of failing hearts or cause the progress from compensated cardiac
      hypertrophy to CHF. 3. Mechanisms governing abnormal myocardial high-energy
      phosphate (HEP) metabolism in hearts with cardiac hypertrophy and CHF are
      unclear. Myocardial energy metabolism studies use both kinetic and thermodynamic
      models. The thermodynamic studies examine the myocardial steady state levels of
      high- and low-energy phosphate, which indicate myocardial energy state or
      phosphorylation potential that is defined by the ratio of [ATP]/([ADP][Pi]). The
      kinetics studies examine the reaction velocity that is regulated by: (i) quantity
      and activity of the key enzymes; (ii) the concentrations of all the substrates
      and products; and (iii) the Michaelis-Menten constants of each substrate of the
      reaction. 4. Significant alterations in myocardial concentrations of
      phosphocreatine (PCr), ATP and ADP, myocardial oxidative phosphorylation (OXPHOS)
      protein expression and substrate preference are found in hearts with
      postinfarction LV remodelling and CHF. However, to define a causal relationship
      is a different matter. 5. Future studies of animal models of LV hypertrophy or
      heart failure using gene manipulation may provide additional insights to answer
      the persisting question of whether limitations of ATP synthetic or transport
      capacities contribute to the pathogenesis of LV remodelling or failure.

PMID- 11985550
TI  - Capsazepine partially inhibits neurally mediated gastric mucus secretion
      following activation of protease-activated receptor 2.
AB  - 1. Protease-activated receptor 2 (PAR2), present in capsaicin-sensitive sensory
      neurons, induces gastric mucus secretion and mucosal cytoprotection. 2. We
      studied the possible cross-talk between PAR2 and vanilloid receptor 1 (VR1). The
      VR1 antagonist capsazepine partially inhibited the PAR2-mediated increase in
      gastric mucus secretion. 3. Thus, activation of VR1 is responsible, at least in
      part, for the neurally mediated mucosal cytoprotection following activation of
      PAR2.

PMID- 11985551
TI  - Detection of small numbers of cells characteristic for haematological disorders
      in peripheral blood (the deep diff).
AB  - We studied cytocentrifuge preparations of peripheral blood mononuclear leucocytes
      in haematological patients with nondiagnostic white cell differential counts.
      This approach (the 'deep diff') enabled the detection of small numbers of
      diagnostically significant cells in a majority of patients. We found ringed
      sideroblasts in 5/7 patients with sideroblastic anaemia and megaloblasts in 9/10
      patients with megaloblastic anaemia. We observed centrocytes in seven patients
      with follicular lymphoma, mantle cells in five patients with mantle cell lymphoma
      and marginal zone cells in five patients with nodal marginal zone lymphoma. We
      detected small percentages of lymphoma cells in cytospins of mononuclear
      leucocytes in 12 patients with large B-cell lymphoma, Burkitt's lymphoma and
      anaplastic large-cell lymphoma. The deep diff was nondiagnostic in 5/6 patients
      with hairy cell leukaemia and in 9/10 patients with Waldenstrom's
      macroglobulinaemia and small lymphocytic lymphoma. In these cases, there were
      insufficient cells to detect light chain restriction. Increased counts of
      leukaemic cells were found in 12/13 patients with acute leukaemia with < 3%
      blasts in the conventional white cell differential. Increased blasts were also
      observed in six patients with refractory anaemia with excess of blasts (RAEB).
      Decreased blasts were found in five patients with aplastic anaemia and in nine
      patients with bone marrow aplasia after intensive chemotherapy. Increased plasma
      cell counts were observed in 13/14 patients with advanced plasma cell myeloma. We
      conclude that the 'deep diff', augmented by immunocytochemistry, may be useful in
      the diagnosis of haematological disorders.

PMID- 11985552
TI  - Activated monocytes and platelet-monocyte aggregates in patients with sickle cell
      disease.
AB  - Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)
      increase endothelial surface receptors that mediate the adherence of sickle
      erythrocytes to the endothelium. Increased circulating levels of these cytokines
      have been found in patients with sickle cell disease (SCD). Monocytes are a
      source of both of these inflammatory mediators; we therefore determined whether
      circulating monocytes were activated in SCD, as defined by intracellular
      expression of these cytokines. Blood was also assayed for the presence of
      platelet-monocyte aggregates (PMAs), as platelet adherence is one possible
      mechanism for monocyte activation. The median percentages of monocytes expressing
      intracellular TNF-alpha and IL-1beta in SCD patients were 6.8 (2.8-17.3) [median
      (range)] and 14.1 (1.3-44.8), respectively. In African-American controls the
      corresponding percentages were 0.3 (0.1-0.5) and 0.4 (0.1-3.0), and in Caucasians
      0.2 (0.1-0.5) and 0.8 (0.8-1.9) (P < 0.001, Kruskal-Wallis). The mean percentage
      (+/- SD) of PMA was 14.0 +/- 8.3 for Caucasian controls, 25.7 +/- 7.3 for African
      American controls, and 45.7 +/- 21.6 for patients with SCD (P < 0.001, RM ANOVA;
      P < 0.05, Newman-Keuls posthoc test). We conclude that there are increased
      circulating PMAs and monocyte activation in patients with SCD.

PMID- 11985553
TI  - Evaluation of flow cytometric enumeration of foetal erythrocytes in maternal
      blood.
AB  - In pregnant women subject to abdominal trauma or other foetomaternal haemorrhage,
      foetal red blood cells containing haemoglobin-F (HbF) can be found in the
      circulation. Recently, a monoclonal antibody to HbF has become commercially
      available, enabling application of a flow cytometric immunofluorescence method
      for accurately determining the concentration of HbF+ red blood cells. We
      demonstrate that white blood cells are included in the cluster selected as red
      blood cells and that these white blood cells exhibit a level of autofluorescence
      that coincides with the fluorescence signal from HbF+ red blood cells. However,
      these white blood cells can be excluded from the analysis, thus preventing
      spuriously increased HbF+ red blood cell counts. We present the results of
      patient samples containing HbF+ red cells as illustrations of the technique and
      as a potential interference by HbF-containing cells of nonfoetal origin. Using
      samples spiked with cord blood, the method is exactly linear with a high
      coefficient of correlation (r=0.997). Furthermore, the assay has excellent
      precision (CV < 2.4%), a low limit of detection (0.12% HbF+ RBC), is independent
      of Rhesus D and can be completed within 1.5 h. This method is suitable for
      accurate determination of foetomaternal haemorrhage.

PMID- 11985554
TI  - Clinical experience with the use of rhG-CSF in secondary autoimmune neutropenia.
AB  - This paper outlines the impact of granulocyte-colony stimulating factor (G-CSF)
      used as a single modality therapy in 17 patients with secondary autoimmune
      neutropenia (S-AIN) who had been treated a multiple number of times previously.
      Fifteen of these patients had demonstrable antineutrophil antibodies and two had
      cellular S-AIN with haemopoietic inhibitory T-cells present in the marrow. Prior
      to treatment, all had had problems with infection. All patients responded within
      7 days of commencement of treatment. Provided G-CSF neutrophil counts were
      maintained above 1 x 109/l, no further infections occurred. This was achievable
      by using G-CSF administered as infrequently as once every 8 days. Eight of the 17
      patients remained on G-CSF, although five switched to the glycosylated form
      because of side-effects. None have developed osteoporosis despite 47.29 patient
      years of total experience with G-CSF. In conclusion both glycosylated and
      nonglycosylated G-CSF can be used effectively in treating AIN on a long-term
      basis.

PMID- 11985555
TI  - Nonchemotherapy drug-induced agranulocytosis: experience of the Strasbourg
      teaching hospital (1985-2000) and review of the literature.
AB  - Agranulocytosis is a life-threatening disorder that frequently occurs as an
      adverse reaction to drugs. The overall incidence of nonchemotherapy drug-induced
      agranulocytosis (DIA) ranges from 2.6 to 10 cases per million patients exposed to
      drugs per year. Although patients experiencing DIA may initially be asymptomatic,
      the severity of the neutropenia usually leads to severe sepsis, requiring
      intravenous broad-spectrum antibiotic therapy. In this setting, old age,
      septicaemia, shock, and the metabolic complications of infection, such as renal
      failure, are poor prognostic variables. The severity of neutropenia (< 0.1 x
      10(9))/l) and its duration (> 10 days) may also impact negatively on the outcome.
      With appropriate management using pre-established procedures, the mortality rate
      is now around 5%. Haematopoietic growth factors have been shown to shorten the
      duration of neutropenia in DIA. However, it has yet to be determined whether
      their use translates into a better outcome in DIA patients experiencing sepsis.
      DIA still remains a rare event. However, given the increased life expectancy and
      subsequent longer exposure to drugs, as well as the development of new agents,
      physicians should be aware of this complication and its management.

PMID- 11985556
TI  - Prevalence of hepatitis C virus and hepatitis G virus in patients with non
      Hodgkin's lymphoma.
AB  - Hepatitis C virus (HCV) and hepatitis G virus (HGV) belong to the same family of
      flaviviridea. A causative role of HCV infection in the pathogenesis of non
      Hodgkin's lymphoma (NHL) has been discussed widely. Little is known about the
      possible association between NHL and HGV discovered recently. In this study, anti
      HCV and HGV-RNA prevalence were investigated in a group of 70 patients with NHL.
      The results were compared to a control group of 70 age- and sex-matched healthy
      subjects. One patient in each group (1.4%) was found to be anti-HCV-positive; the
      difference was not statistically significant (P > 0.05). Five subjects in the
      patient group (7.1%) were positive for HGV-RNA, while a single subject was
      positive in the control group (1.4%); the difference was not statistically
      significant (P > 0.05). Odds ratios for anti-HCV and HGV-RNA were 1 and 5.30,
      respectively. Our findings suggest that neither HCV nor HGV are causative or
      contributing factors in the aetiopathogenesis of NHL.

PMID- 11985557
TI  - Burkitt's lymphoma: single-centre experience with modified BFM protocol.
AB  - Burkitt's lymphoma is a rare aggressive lymphoma, which responds poorly to
      standard chemotherapy regimens used to treat high-grade non-Hodgkin's lymphoma
      (NHL). The use of intensive chemotherapy protocols using alkylating agents and
      intensive CNS prophylaxis has dramatically altered prognosis. We have treated
      eight patients with Burkitt's lymphoma with a modified BFM protocol. The dose of
      methotrexate was reduced from 5 g/m2 to 1.5 g/m2 with the aim of reducing
      toxicity. Seven patients received a total of six cycles of chemotherapy each and
      one patient received five cycles of chemotherapy. Each cycle included high-dose
      methotrexate, an alkylating agent (ifosphamide or cyclophosphamide) and two
      triple intrathecal injections of chemotherapy. Two patients with bulky abdominal
      disease in addition received an autologous stem cell transplant. The regimen was
      well tolerated with minimal toxicity. At a median follow-up of 16 months (range
      10-28), six of the eight patients (75%) were alive and in complete remission. Two
      patients relapsed, one 24 months post-BFM chemotherapy and the other 1-month post
      autologous stem cell transplantation and 2 months post-BFM chemotherapy.

PMID- 11985558
TI  - Flow cytometric analysis of platelet activation under calcium ion-chelating
      conditions.
AB  - Platelet activation and aggregation results in factitious counting and sizing in
      routine haematology testing. In this study, the possibility of platelet
      activation in anticoagulated solutions was examined. Whole blood was examined
      using an automated counter and a flow cytometer before and after strong vortex
      agitation. Blood treated with ethylenediaminetetraacetic acid (EDTA) exhibited
      platelet activation both pre- and postagitation but activated platelets did not
      cause platelet aggregation. With sodium citrate, platelets were only minimally
      activated both pre- and postagitation. Heparin-treated blood exhibited minimal
      platelet activation preagitation, but agitation resulted in strong platelet
      activation and aggregation. Platelet size was increased by agitation in blood
      with EDTA and with sodium citrate, in association with significant increases in
      mean platelet volume (MPV) and platelet distribution width (PDW), but MPV and PDW
      were significantly higher in EDTA solution than in sodium citrate solution.
      Change in platelet size was observed even in the presence of EDTA, indicating
      that careful sampling and processing are needed in the collection of specimens.
      Specimens obtained from patients with EDTA-dependent pseudothrombocytopenia
      exhibited the same level of activation as controls, although platelets exhibited
      aggregation in such specimens. In conclusion, platelet activation involving
      platelet size change can occur in the absence of calcium ions in blood treated
      with EDTA.

PMID- 11985559
TI  - The hyperaggregability of platelets from normal pregnancy is mediated through
      thromboxane A2 and cyclic AMP pathways.
AB  - There is substantial evidence of increased platelet reactivity in vivo and in
      vitro during pregnancy, with the risk of developing pre-eclampsia. In this study,
      platelet function was studied during 28-40 weeks of gestation in a group of women
      who remained normotensive and in a group of nonpregnant female controls. Platelet
      aggregation stimulated by thrombin and adenosine diphosphate was markedly
      enhanced in washed platelets from pregnant subjects. Thrombin (0.04 U/ml)-evoked
      increases in intracellular Ca+2 mobilization of Fura 2-AM-loaded platelets were
      also enhanced in pregnant subjects. The binding of fluorescein isothiocyanate
      (FITC)-triflavin (2 microg/ml) to the glycoprotein IIb/IIIa complex in thrombin
      activated platelets did not differ significantly between the nonpregnant and
      pregnant groups. Thromboxane A2 (TXA2) formation in both resting and thrombin
      activated platelets from pregnant subjects was significantly greater than from
      nonpregnant subjects. Levels of cyclic adenosine monophosphate (cAMP) in both
      resting and prostaglandin E1-treated platelets (10 micromol/l) from pregnant
      subjects were significantly lower than those from nonpregnant subjects. There
      were no significant differences between nonpregnant and pregnant subjects in
      platelet cAMP levels in the presence of imidazole (600 micromol/l) and
      indomethacin (500 micromol/l). Intracellular pH values in platelets were measured
      spectrofluorometrically using the fluorescent probe, BCECF-AM. The increase in
      intracellular pH stimulated by thrombin (0.04 U/ml) in pregnant subjects was
      markedly greater than that in observed nonpregnant subjects. We conclude that the
      agonist-induced hyperaggregability of platelets in normal pregnancy may be due,
      at least partly, to stimulation of the Na+/H+ exchanger and subsequently to
      elevated intracellular Ca+2 mobilization, and then to increased TXA2 formation
      and a lowered level of cAMP, which leads to further increases in intracellular
      Ca+2 mobilization, and finally to enhanced platelet aggregation.

PMID- 11985560
TI  - Splenectomy in a case of splenic vein thrombosis unmasks essential
      thrombocythemia.
AB  - We report a patient with splenic vein thrombosis (SVT) in whom splenectomy
      resulted in the unmasking of essential thrombocythemia (ET). He had portal
      hypertension with haematemesis, resulting in anaemia requiring repeated blood
      transfusions. Investigations revealed SVT. Following splenectomy, he suffered a
      transient ischaemic attack episode, associated with persistent thrombocytosis (>
      2000 x 10(9)/l). Other myeloproliferative disorders were excluded and a diagnosis
      of ET was established. He responded to hydroxyurea but, due to financial
      constraints, he discontinued treatment and subsequently relapsed. The association
      of ET with SVT is rare and the diagnosis of ET was missed initially as the
      platelet count was normal prior to splenectomy.

PMID- 11985561
TI  - Spherocytes, irregularly contracted cells or ... schistocytes?

PMID- 11985562
TI  - Lessons from the audit of invasive cervical cancer.

PMID- 11985563
TI  - Bethesda 2001.
AB  - The Bethesda system (TBS) for reporting cervical/vaginal cytological diagnoses
      was originally developed in 1988 at a National Cancer Institute (NCI) workshop
      convened to consider the benefits of increased standardization in the diagnostic
      reports provided by cytology laboratories. It rapidly gained acceptance in
      laboratory practice in the USA and beyond and three years later the NCI sponsored
      another workshop to assess the use of TBS in practice and consider areas for
      improvement. Subsequently an illustrated guide was published.

PMID- 11985564
TI  - Expression of CD40, CD44, bcl-2 antigens and rate of cell proliferation on fine
      needle aspirates from metastatic melanoma.
AB  - The clinical behaviour of melanoma is often unpredictable using clinical and
      histological criteria. Tumour cell markers related to cell cycle regulation,
      apoptosis, cell-cell interactions and cell proliferation might improve the
      possibility of predicting the clinical course of melanoma. The aim of the present
      study was to refine prognostic criteria by an immunocytochemical investigation of
      CD44, CD40, bcl-2 antigens and cell proliferation in tumour cells aspirated from
      metastases of malignant melanoma. CD40 is a cell surface receptor shown to be
      expressed by lymphomas as well as carcinomas, and is thought to play a central
      role in the process of tumour progression. CD44 is a transmembrane glycoprotein,
      which is involved in growth signal transmission of importance in the binding of
      tumour cells to endothelium, cell migration and enhancement of cell motility,
      which makes it of interest to study in relation to the metastasizing capacity of
      tumours. The bcl-2 protein is active in the process of programmed cell death
      (apoptosis) as an antiapoptotic agent and its expression may reflect tumour
      progression. Mean/median percentages of tumour cell positivity were 8.5/3.0 for
      CD40, 76.1/86.3 for CD44 and 7.4/3.3 for bcl-2. A significant correlation was
      observed between expression of apoptosis-associated bcl-2 antigen and overall
      survival (r = 0.33). The CD44 positive cell fraction was higher in patients with
      short overall survival than those with long survival but this difference was not
      statistically significant. The expression of CD40 did not correlate with overall
      survival. The mean/median proliferation fraction assessed by MIB-1 monoclonal
      antibody was 25.8/23.9 and showed a significant correlation with survival after
      diagnosis of melanoma metastasis (r = 0.32). Lack of bcl-2 expression and a high
      proportion of tumour cells expressing Ki-67 antigen are predictors of poor
      prognosis that are independent of the traditionally accepted Breslow's thickness
      of the primary melanomas.

PMID- 11985565
TI  - Papillary neoplasms of the breast: clues in fine needle aspiration cytology.
AB  - Papillary neoplasms of the breast include a wide spectrum of mammary lesions. The
      differential diagnosis of benign and malignant lesions can be problematic not
      only cytologically, but also histopathologically. Aspiration smears can
      demonstrate that cytological differentiation is feasible. A retrospective study
      of 30 cases of papillary tumour of the breast, 15 papillary carcinomas and 15
      papillomas, was performed to find the cytological differences between the
      pathologies. Cytological samples of papillary carcinomas were characterized by an
      abundance of cellular material, three-dimensional papillary clusters without
      fibrovascular connective tissue cores, small papillae arranged in cell balls,
      tall columnar cells and isolated naked nuclei. Numerous haemosiderin-laden
      macrophages were seen. There were no eosinophilic bipolar cytoplasmic granules,
      bipolar naked nuclei or apocrine metaplasia. In the papillomas there was less
      material; the papillae had cohesive stalks surrounded by columnar cells in a
      honeycomb pattern. We also found fewer small papillae and isolated columnar
      cells. In addition, the presence of apocrine metaplasia and bipolar naked nuclei
      was noted. We suggest that papillary carcinoma of the breast can be diagnosed by
      cytology and differentiated from papilloma.

PMID- 11985566
TI  - Aspiration cytology of Hashimoto's thyroiditis in an endemic area.
AB  - Fine needle aspiration (FNA) plays a significant role in the diagnosis of thyroid
      lesions due to its simplicity and low cost. Hashimoto's thyroiditis (HT) is the
      second most common thyroid lesion next to endemic goitre diagnosed on FNA in
      iodine (I2) deficient areas. Data on its incidence, prevalence and
      clinicopathological features in I2 deficient areas is scanty compared to I2
      sufficient areas. In the present study the patients presented with HT a decade
      earlier than reported in I2 sufficient areas. Presentation as a nodular thyroid
      is common. Diagnosis of HT is likely to be missed in smears showing cytological
      evidence of hyperplasia or abundant colloid. HT was concurrent in 20 cases of
      endemic goitre. Careful screening for Hurthle cell change and lymphocytic
      infiltration into follicular cells should be carried out. In equivocal cases
      multiple punctures and immunological investigations are helpful. In antibody
      negative cases repeat FNA at follow-up is useful. Marked lymphocytic infiltration
      and Hurthle cell change may indicate a hypothyroid state but hormonal levels are
      required for clinical management.

PMID- 11985567
TI  - Evidence for direct learning curve for technique on change of cervical sampling
      device.
AB  - The recommended sampling device within the NHS Cervical Screening Programme is
      the Aylesbury spatula. A local decision was taken to decrease brush usage (either
      alone or in combination) by 50% from an initial level of 41.8%, with an initial
      inadequate smear rate of 9.93%. This was managed by controlling smear taking
      equipment through provision of smear taking kits. The monthly inadequate rate
      unexpectedly rose to 17.8% before dropping back to previous levels. Brush usage
      overall fell to 35.2%, with a corresponding increase in spatula use. The possible
      reasons for this are discussed. The facts suggest that these changes were
      directly linked, and that there is a learning curve with change of sampling
      device and that a rise in the inadequate rate should be expected under these
      circumstances.

PMID- 11985568
TI  - Method of producing tissue sections from endometrial scrapings.
AB  - Endometrial cytology is important not only for observing cytological findings,
      but also for assessing histological architecture. Therefore, we attempted to
      produce a histological preparation from the sample using an automatic fixation
      apparatus (ACF 1000) which employs a membrane filter method. After observation of
      the cytological features, the cover slip was removed and a paraffin-embedded
      section was prepared. Producing a histological section from a cytological
      specimen prepared with the ACF 1000 apparatus was more useful and easier than
      with the techniques described to date. Peelability of the cell was avoided by
      using a silane-coated membrane filter. Observation of the same cell cluster as
      that observed in the cytological sample was also facilitated in the histological
      section by this technique.

PMID- 11985569
TI  - Epithelioid malignant peripheral nerve sheath tumour: case report and review of
      the previously published cases.

PMID- 11985570
TI  - Foam cells in nipple aspiration fluid.

PMID- 11985571
TI  - Is it reality or an illusion that liquid-based cytology is better than
      conventional cervical smears?

PMID- 11985572
TI  - Is it reality or an illusion that liquid-based cytology is better than
      conventional cervical smears?

PMID- 11985574
TI  - Three detailed hypotheses implicating oxidative damage to mitochondria as a major
      driving force in homeotherm aging.

PMID- 11985575
TI  - The mitochondrial-lysosomal axis theory of aging: accumulation of damaged
      mitochondria as a result of imperfect autophagocytosis.
AB  - Cellular manifestations of aging are most pronounced in postmitotic cells, such
      as neurons and cardiac myocytes. Alterations of these cells, which are
      responsible for essential functions of brain and heart, are particularly
      important contributors to the overall aging process. Mitochondria and lysosomes
      of postmitotic cells suffer the most remarkable age-related alterations of all
      cellular organelles. Many mitochondria undergo enlargement and structural
      disorganization, while lysosomes, which are normally responsible for
      mitochondrial turnover, gradually accumulate an undegradable, polymeric,
      autofluorescent material called lipofuscin, or age pigment. We believe that these
      changes occur not only due to continuous oxidative stress (causing oxidation of
      mitochondrial constituents and autophagocytosed material), but also because of
      the inherent inability of cells to completely remove oxidatively damaged
      structures (biological 'garbage'). A possible factor limiting the effectiveness
      of mitochondial turnover is the enlargement of mitochondria which may reflect
      their impaired fission. Non-autophagocytosed mitochondria undergo further
      oxidative damage, resulting in decreasing energy production and increasing
      generation of reactive oxygen species. Damaged, enlarged and functionally
      disabled mitochondria gradually displace normal ones, which cannot replicate
      indefinitely because of limited cell volume. Although lipofuscin-loaded lysosomes
      continue to receive newly synthesized lysosomal enzymes, the pigment is
      undegradable. Therefore, advanced lipofuscin accumulation may greatly diminish
      lysosomal degradative capacity by preventing lysosomal enzymes from targeting to
      functional autophagosomes, further limiting mitochondrial recycling. This
      interrelated mitochondrial and lysosomal damage irreversibly leads to functional
      decay and death of postmitotic cells.

PMID- 11985576
TI  - The reductive hotspot hypothesis of mammalian aging: membrane metabolism
      magnifies mutant mitochondrial mischief.
AB  - A severe challenge to the idea that mitochondrial DNA mutations play a major role
      in the aging process in mammals is that clear loss-of-function mutations
      accumulate only to very low levels (under 1% of total) in almost any tissue, even
      by very old age. Their accumulation is punctate: some cells become nearly devoid
      of wild-type mitochondrial DNA and exhibit no activity for the partly
      mitochondrially encoded enzyme cytochrome c oxidase. Such cells accumulate in
      number with aging, suggesting that they survive indefinitely, which is itself
      paradoxical. The reductive hotspot hypothesis suggests that these cells adjust
      their metabolism to use plasma membrane electron transport as a substitute for
      the mitochondrial electron transport chain in the reoxidation of reduced
      dinucleotides, and that, like mitochondrial electron transport, this process is
      imperfect and generates superoxide as a side-effect. This superoxide, generated
      on the outside of the cell, can potentially initiate classical free radical
      chemistry including lipid peroxidation chain reactions in circulating material
      such as lipoproteins. These, in turn, can be toxic to mitochondrially nonmutant
      cells that import them to satisfy their cholesterol requirements. Thus, the
      relatively few cells that have lost oxidative phosphorylation capacity may be
      toxic to the rest of the body. In this minireview, recent results relevant to
      this hypothesis are surveyed and approaches to intervening in the proposed
      process are discussed.

PMID- 11985577
TI  - Mitochondrial DNA deletion mutations: a causal role in sarcopenia.
AB  - Mitochondrial DNA (mtDNA) deletion mutations accumulate with age in tissues of a
      variety of species. Although the relatively low calculated abundance of these
      deletion mutations in whole tissue homogenates led some investigators to suggest
      that these mutations do not have any physiological impact, their focal and
      segmental accumulation suggests that they can, and do, accumulate to levels
      sufficient to affect the metabolism of a tissue. This phenomenon is most clearly
      demonstrated in skeletal muscle, where the accumulation of mtDNA deletion
      mutations remove critical subunits that encode for the electron transport system
      (ETS). In this review, we detail and provide evidence for a molecular basis of
      muscle fiber loss with age. Our data suggest that the mtDNA deletion mutations,
      which are generated in tissues with age, cause muscle fiber loss. Within a fiber,
      the process begins with a mtDNA replication error, an error that results in a
      loss of 25-80% of the mitochondrial genome. This smaller genome is replicated
      and, through a process not well understood, eventually comprises the majority of
      mtDNA within the small affected region of the muscle fiber. The preponderance of
      the smaller genomes results in a dysfunctional ETS in the affected area. As a
      consequence of both the decline in energy production and the increase in
      oxidative damage in the region, the fiber is no longer capable of self
      maintenance, resulting in the observed intrafiber atrophy and fiber breakage. We
      are therefore proposing that a process contained within a very small region of a
      muscle fiber can result in breakage and loss of muscle fiber from the tissue.

PMID- 11985578
TI  - Tissue factor pathway inhibitor: a possible mechanism of action.
AB  - We have analyzed several mathematical models that describe inhibition of the
      factor VIIa-tissue factor complex (VIIa-TF) by tissue factor pathway inhibitor
      (TFPI). At the core of these models is a common mechanism of TFPI action
      suggesting that only the Xa-TFPI complex is the inhibitor of the extrinsic tenase
      activity. However, the model based on this hypothesis could not explain well all
      the available experimental data. Here, we show that a good quantitative
      description of all experimental data could be achieved in a model that contains
      two more assumptions. The first assumption is based on the hypothesis originally
      proposed by Baugh et al. [Baugh, R.J., Broze, G.J. Jr & Krishnaswamy, S. (1998)
      J. Biol. Chem. 273, 4378-4386], which suggests that TFPI could inhibit the enzyme
      product complex Xa-VIIa-TF. The second assumption proposes an interaction between
      the X-VIIa-TF complex and the factor Xa-TFPI complex. Experiments to test these
      hypotheses are suggested.

PMID- 11985579
TI  - Protein methylation as a marker of aspartate damage in glucose-6-phosphate
      dehydrogenase-deficient erythrocytes: role of oxidative stress.
AB  - The 'Mediterranean' variant of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency is due to the C563CT point mutation, leading to replacement of Ser
      with Phe at position 188, resulting in acute haemolysis triggered by oxidants.
      Previous work has shown increased formation of altered aspartate residues in
      membrane proteins during cell ageing and in response to oxidative stress in
      normal erythrocytes. These abnormal residues are specifically recognized by the
      repair enzyme L-isoaspartate (d-aspartate) protein O-methyltransferase (PCMT; EC
      2.1.1.77). The aim of this work was to study the possible involvement of protein
      aspartate damage in the mechanism linking the G6PD defect and erythrocyte injury,
      through oxidative stress. Patients affected by G6PD deficiency (Mediterranean
      variant) were selected. In situ methylation assays were performed by incubating
      intact erythrocytes in the presence of methyl-labelled methionine. Altered
      aspartate residues were detected in membrane proteins by methyl ester
      quantification. We present here evidence that, in G6PD-deficient erythrocytes,
      damaged residues are significantly increased in membrane proteins, in parallel
      with the decay of pyruvate kinase activity, used as a cell age marker.
      Erythrocytes from patients were subjected to oxidative stress in vitro, by
      treatment with t-butylhydroperoxide, monitored by a rise in concentration of both
      methaemoglobin and thiobarbituric acid-reactive substances. L-Isoaspartate
      residues increased dramatically in G6PD-deficient erythrocytes in response to
      such treatment, compared with baseline conditions. The increased susceptibility
      of G6PD-deficient erythrocytes to membrane protein aspartate damage in response
      to oxidative stress suggests the involvement of protein deamidation/isomerization
      in the mechanisms of cell injury and haemolysis.

PMID- 11985580
TI  - Electrostatic properties of the structure of the docking and dimerization domain
      of protein kinase A IIalpha.
AB  - The structure of the N-terminal docking and dimerization domain of the type
      IIalpha regulatory subunit (RIIalpha D/D) of protein kinase A (PKA) forms a
      noncovalent stand-alone X-type four-helix bundle structural motif, consisting of
      two helix-loop-helix monomers. RIIalpha D/D possesses a strong hydrophobic core
      and two distinct, exposed faces. A hydrophobic face with a groove is the site of
      protein-protein interactions necessary for subcellular localization. A highly
      charged face, opposite to the former, may be involved in regulation of protein
      protein interactions as a result of changes in phosphorylation state of the
      regulatory subunit. Although recent studies have addressed the hydrophobic
      character of packing of RIIalpha D/D and revealed the function of the hydrophobic
      face as the binding site to A-kinase anchoring proteins (AKAPs), little attention
      has been paid to the charges involved in structure and function. To examine the
      electrostatic character of the structure of RIIalpha D/D we have predicted mean
      apparent pKa values, based on Poisson-Boltzmann electrostatic calculations, using
      an ensemble of calculated dimer structures. We propose that the helix promoting
      sequence Glu34-X-X-X-Arg38 stabilizes the second helix of each monomer, through
      the formation of a (i, i +4) side chain salt bridge. We show that a weak inter
      helical hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary
      packing and may be responsible for discriminating from alternative quaternary
      packing of the two monomers. We also show that an inter-monomer hydrogen bond
      between Asp30-Arg40 contributes to quaternary packing. We propose that the
      charged face comprising of Asp27-Asp30-Glu34-Arg38-Arg40-Glu41-Arg43-Arg44 may be
      necessary to provide flexibility or stability in the region between the C
      terminus and the interdomain/autoinhibitory sequence of RIIalpha, depending on
      the activation state of PKA. We also discuss the structural requirements
      necessary for the formation of a stacked (rather than intertwined) dimer, which
      has consequences for the orientation of the functionally important and distinct
      faces.

PMID- 11985581
TI  - ORF6 from the clavulanic acid gene cluster of Streptomyces clavuligerus has
      ornithine acetyltransferase activity.
AB  - The clinically used beta-lactamase inhibitor clavulanic acid is produced by
      fermentation of Streptomyces clavuligerus. The orf6 gene of the clavulanic acid
      biosynthetic gene cluster in S. clavuligerus encodes a protein that shows
      sequence homology to ornithine acetyltransferase (OAT), the fifth enzyme of the
      arginine biosynthetic pathway. Orf6 was overexpressed in Escherichia coli (at
      approximately 15% of total soluble protein by SDS/PAGE analysis) indicating it
      was not toxic to the host cells. The recombinant protein was purified (to > 95%
      purity) by a one-step technique. Like other OATs it was synthesized as a
      precursor protein which underwent autocatalytic internal cleavage in E. coli to
      generate alpha and beta subunits. Cleavage was shown to occur between the alanine
      and threonine residues in a KGXGMXXPX--(M/L)AT (M/L)L motif conserved within all
      identified OAT sequences. Gel filtration and native electrophoresis analyses
      implied that the ORF6 protein was an alpha2beta2 heterotetramer and direct
      evidence for this came from mass spectrometric analyses. Although anomalous
      migration of the beta subunit was observed by standard SDS/PAGE analysis, which
      indicated the presence of two bands (as previously observed for other OATs), mass
      spectrometric analyses did not reveal any evidence for post-translational
      modification of the beta subunit. Extended denaturation with SDS before PAGE
      resulted in observation of a single major beta subunit band. Purified ORF6 was
      able to catalyse the reversible transfer of an acetyl group from N
      acetylornithine to glutamate, but not the formation of N-acetylglutamate from
      glutamate and acetyl-coenzyme A, nor (detectably) the hydrolysis of N
      acetylornithine. Mass spectrometry also revealed the reaction proceeds via
      acetylation of the beta subunit.

PMID- 11985582
TI  - Crystal structure of the catalytic domain of a human thioredoxin-like protein.
AB  - Thioredoxin is a ubiquitous dithiol oxidoreductase found in many organisms and
      involved in numerous biochemical processes. Human thioredoxin-like protein
      (hTRXL) is differentially expressed at different development stages of human
      fetal cerebrum and belongs to an expanding family of thioredoxins. We have solved
      the crystal structure of the recombinant N-terminal catalytic domain (hTRXL-N) of
      hTRXL in its oxidized form at 2.2-A resolution. Although this domain shares a
      similar three-dimensional structure with human thioredoxin (hTRX), a unique
      feature of hTRXL-N is the large number of positively charged residues distributed
      around the active site, which has been implicated in substrate specificity.
      Furthermore, the hTRXL-N crystal structure is monomeric while hTRX is dimeric in
      its four crystal structures (reduced, oxidized, C73S and C32S/C35S mutants)
      reported to date. As dimerization is the key regulatory factor in hTRX, the
      positive charge and lack of dimer formation of hTRXL-N suggest that it could
      interact with the acidic amino-acid rich C-terminal region, thereby suggesting a
      novel regulation mechanism.

PMID- 11985583
TI  - Purification and biochemical characterization of some of the properties of
      recombinant human kynureninase.
AB  - Recombinant human kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) was purified
      to homogeneity (60-fold) from Spodoptera frugiperda (Sf9) cells infected with
      baculovirus containing the kynureninase gene. The purification protocol comprised
      ammonium sulfate precipitation and several chromatographic steps, including DEAE
      Sepharose CL-6B, hydroxyapatite, strong anionic and cationic separations. The
      purity of the enzyme was determined by SDS/PAGE, and the molecular mass verified
      by MALDI-TOF MS. The monomeric molecular mass of 52.4 kDa determined was > 99.99%
      of the predicted molecular mass. A UV absorption spectrum of the holoenzyme
      resulted in a peak at 432 nm. The optimum pH was 8.25 and the enzyme displayed a
      strong dependence on the ionic strength of the buffer for optimum activity. This
      cloned enzyme was highly specific for 3-hydroxykynurenine (Km = 3.0 microm +/-
      0.10) and was inhibited by L-kynurenine (Ki = 20 microm), d-kynurenine (Ki = 12
      microm) and a synthetic substrate analogue D,L-3,7-dihydroxydesaminokynurenine
      (Ki = 100 nm). The activity/concentration profile for kynureninase from this
      source was sigmoidal in all instances. There appeared to be partial inhibition by
      substrate, and excess pyridoxal 5'-phosphate was found to be inhibitory.

PMID- 11985584
TI  - Kinetic analysis of hydroxylation of saturated fatty acids by recombinant
      P450foxy produced by an Escherichia coli expression system.
AB  - Cytochrome P450foxy (P450foxy, CYP505) is a fused protein of cytochrome P450
      (P450) and its reductase isolated from the fungus Fusarium oxysporum, which
      catalyzes the subterminal (omega-1 approximately omega-3) hydroxylation of fatty
      acids. Here, we produced, purified and characterized a fused recombinant protein
      (rP450foxy) using the Escherichia coli expression system. Purified rP450foxy was
      catalytically and spectrally indistinguishable from the native protein, but most
      of the rP450foxy was recovered in the soluble fraction of E. coli cells unlike
      the membrane-bound native protein. The results are consistent with our notion
      that the native protein is targeted to the membrane by a post-translational
      modification mechanism. We also discovered that P450foxy could use shorter
      saturated fatty acid chains (C9 and C10) as a substrate. The regiospecificity
      (omega-1 approximately omega-3) of hydroxylation due to the enzymatic reaction
      for the short substrates (decanoate, C10; undecanoate, C11) was the same as that
      for longer substrates. Steady state kinetic studies showed that the kcat values
      for all substrates tested (C9-C16) were of the same magnitude (1200-1800 min-1),
      whereas the catalytic efficiency (kcat/Km) was higher for longer fatty acids.
      Substrate inhibition was observed with fatty acid substrates longer than C13, and
      the degree of inhibition increased with increasing chain length. This substrate
      inhibition was not apparent with P450BM3, a bacterial counterpart of P450foxy,
      which was the first obvious difference in their catalytic properties to be
      identified. Kinetic data were consistent with the inhibition due to binding of
      the second substrate. We discuss the inhibition mechanism based on differences
      between P450foxy and P450BM3 in key amino acid residues for substrate binding.

PMID- 11985585
TI  - Properties of group I allergens from grass pollen and their relation to cathepsin
      B, a member of the C1 family of cysteine proteinases.
AB  - Expansins are a family of proteins that catalyze pH-dependent long-term extension
      of isolated plant cell walls. They are divided into two groups, alpha and beta,
      the latter consisting of the grass group I pollen allergens and their vegetative
      homologs. Expansins are suggested to mediate plant cell growth by interfering
      with either structural proteins or the polysaccharide network in the cell wall.
      Our group reported papain-like properties of beta-expansin of Timothy grass
      (Phleum pratense) pollen, Phl p 1, and suggested that cleavage of cell wall
      structural proteins may be the underlying mechanism of expansin-mediated wall
      extension. Here, we report additional data showing that beta-expansins resemble
      ancient and modern cathepsin B, which is a member of the papain (C1) family of
      cysteine proteinases. Using the Pichia pastoris expression system, we show that
      cleavage of inhibitory prosequences from the recombinant allergen is facilitated
      by its N-glycosylation and that the truncated, activated allergen shows
      proteolytic activity, resulting in very low stability of the protein. We also
      show that deglycosylated, full-length allergen is not activated efficiently and
      therefore is relatively stable. Motif and homology search tools detected
      significant similarity between beta-expansins and cathepsins of modern animals as
      well as the archezoa Giardia lamblia, confirming the presence of inhibitory
      prosequences, active site and other functional amino-acid residues, as well as a
      conserved location of these features within these molecules. Lastly, we
      demonstrate by site-directed mutagenesis that the conserved His104 residue is
      involved in the catalytic activity of beta-expansins. These results indicate a
      common origin of cathepsin B and beta-expansins, especially if taken together
      with their previously known biochemical properties.

PMID- 11985586
TI  - The role of hydrophobic active-site residues in substrate specificity and acyl
      transfer activity of penicillin acylase.
AB  - Penicillin acylase of Escherichia coli catalyses the hydrolysis and synthesis of
      beta-lactam antibiotics. To study the role of hydrophobic residues in these
      reactions, we have mutated three active-site phenylalanines. Mutation of
      alphaF146, betaF24 and betaF57 to Tyr, Trp, Ala or Leu yielded mutants that were
      still capable of hydrolysing the chromogenic substrate 2-nitro-5
      [(phenylacetyl)amino]-benzoic acid. Mutations on positions alphaF146 and betaF24
      influenced both the hydrolytic and acyl transfer activity. This caused changes in
      the transferase/hydrolase ratios, ranging from a 40-fold decrease for alphaF146Y
      and alphaF146W to a threefold increase for alphaF146L and betaF24A, using 6
      aminopenicillanic acid as the nucleophile. Further analysis of the betaF24A
      mutant showed that it had specificity constants (kcat/Km) for p
      hydroxyphenylglycine methyl ester and phenylglycine methyl ester that were
      similar to the wild-type values, whereas the specificity constants for p
      hydroxyphenylglycine amide and phenylglycine amide had decreased 10-fold, due to
      a decreased kcat value. A low amidase activity was also observed for the
      semisynthetic penicillins amoxicillin and ampicillin and the cephalosporins
      cefadroxil and cephalexin, for which the kcat values were fivefold to 10-fold
      lower than the wild-type values. The reduced specificity for the product and the
      high initial transferase/hydrolase ratio of betaF24A resulted in high yields in
      acyl transfer reactions.

PMID- 11985587
TI  - Identification of novel membrane proteins by searching for patterns in hydropathy
      profiles.
AB  - A technique has been developed to search a proteome database for new members of a
      functional class of membrane protein. It takes advantage of the highly conserved
      secondary structure of functionally related membrane proteins. Such proteins
      typically have the same number of transmembrane domains located at similar
      relative positions in their polypeptide sequence. This gives rise to a
      characteristic pattern of peaks in their hydropathy profiles. To conduct a
      search, each member of a polypeptide database is converted to a hydropathy
      profile, peaks are automatically detected, and the pattern of peaks is compared
      with a template. A template was designed for the acetylcholine (ACh) and glycine
      receptors of the cys-loop receptor superfamily. The key feature was a closely
      spaced triplet of hydropathy peaks bracketed by deep valleys. When applied to the
      human proteome the search procedure retrieved 153 profiles with a receptor-like
      triplet of peaks. The approach was highly selective with 70% of the retrieved
      profiles annotated as known or putative receptors. These included ACh, glycine,
      gamma-amino butyric acid and serotonin receptors, which are all related by
      sequence. However, ionotropic glutamate receptors, which have almost no sequence
      homology with ACh receptors, were also retrieved. Thus, the strategy can find
      members of a functional class that cannot be identified by sequence alignment. To
      demonstrate that the strategy can easily be extended to other membrane protein
      families, a template was developed for the neurotransmitter/Na+ symporter family,
      and similar results were obtained. This approach should prove a useful adjunct to
      sequence-based retrieval tools when searching for novel membrane proteins.

PMID- 11985588
TI  - Thiol-modifying inhibitors for understanding squalene cyclase function.
AB  - The function of squalene-hopene cyclase from Alicyclobacillus acidocaldarius was
      studied by labelling critical cysteine residues of the enzyme, either native or
      inserted by site-directed mutagenesis, with different thiol-reacting molecules.
      The access of the substrate to the active centre cavity through a nonpolar
      channel that contains a narrow constriction harbouring a cysteine residue (C435)
      was probed by labelling experiments on both a C435S mutant, lacking C435 of the
      channel constriction, and a C25S/C50S/C455S/C537S mutant, bearing C435 as the
      only cysteine residue. Labelling experiments with tritiated 3-carboxy-4
      nitrophenyl-dithio-1,1',2-trisnorsqualene (CNDT-squalene) showed that the
      cysteine residue at the channel constriction was covalently modified by the
      squalene-like inhibitor. Time-dependent inactivation of the C25S/C50S/C455S/C537S
      mutant by a number of squalene analogues and other agents with thiol-modifying
      activity suggested that modifying C435 caused the obstruction of the channel
      constriction thus blocking access of the substrate to the active site. The
      tryptic fragment comprising C435 of the quadruple mutant labelled with the most
      effective inhibitor had the expected altered molecular mass, as determined by LC
      ESI-MS measurements. The arrangement of the substrate in the active site cavity
      was studied by using thiol reagents as probes in labelling experiments with the
      double mutant D376C/C435S in which D376, supposedly the substrate-protonating
      residue, was substituted by cysteine. The inhibitory effect was evaluated in
      terms of the reduced ability to cyclize oxidosqualene, as the mutant is unable to
      catalyse the reaction of squalene to hopene. Among the inhibitors tested, the
      substrate analogue squalene-maleimide proved to be a very effective time
      dependent inhibitor.

PMID- 11985589
TI  - The role of zinc in the methylation of the coenzyme M thiol group in
      methanol:coenzyme M methyltransferase from Methanosarcina barkeri.
AB  - Methanol:coenzyme M methyltransferase from methanogenic archaea is a cobalamin
      dependent enzyme composed of three different subunits: MtaA, MtaB and MtaC. MtaA
      is a zinc protein that catalyzes the methylation of coenzyme M (HS-CoM) with
      methylcob(III)alamin. We report zinc XAFS (X-ray absorption fine structure)
      results indicating that, in the absence of coenzyme M, zinc is probably
      coordinated by a single sulfur ligand and three oxygen or nitrogen ligands. In
      the presence of coenzyme M, one (N/O)-ligand was replaced by sulfur, most likely
      due to ligation of the thiol group of coenzyme M. Mutations in His237 or Cys239,
      which are proposed to be involved in ligating zinc, resulted in an over 90% loss
      in enzyme activity and in distinct changes in the zinc ligands. In the His237-
      >Ala and Cys239-->Ala mutants, coenzyme M also seemed to bind efficiently by
      ligation to zinc indicating that some aspects of the zinc ligand environment are
      surprisingly uncritical for coenzyme M binding.

PMID- 11985590
TI  - The refolding of type II shikimate kinase from Erwinia chrysanthemi after
      denaturation in urea.
AB  - Shikimate kinase was chosen as a convenient representative example of the
      subclass of alpha/beta proteins with which to examine the mechanism of protein
      folding. In this paper we report on the refolding of the enzyme after
      denaturation in urea. As shown by the changes in secondary and tertiary structure
      monitored by far UV circular dichroism (CD) and fluorescence, respectively, the
      enzyme was fully unfolded in 4 m urea. From an analysis of the unfolding curve in
      terms of the two-state model, the stability of the folded state could be
      estimated as 17 kJ.mol-1. Approximately 95% of the enzyme activity could be
      recovered on dilution of the urea from 4 to 0.36 m. The results of spectroscopic
      studies indicated that refolding occurred in at least four kinetic phases, the
      slowest of which (k = 0.009 s-1) corresponded with the regain of shikimate
      binding and of enzyme activity. The two most rapid phases were associated with a
      substantial increase in the binding of 8-anilino-1-naphthalenesulfonic acid with
      only modest changes in the far UV CD, indicating that a collapsed intermediate
      with only partial native secondary structure was formed rapidly. The relevance of
      the results to the folding of other alpha/beta domain proteins is discussed.

PMID- 11985591
TI  - Expression pattern in the antennae of a newly isolated lepidopteran Gq protein
      alpha subunit cDNA.
AB  - From the antennae of the moth Mamestra brassicae, we have identified a
      lepidopteran G protein alpha subunit belonging to the Gq family, through
      immunological detection in crude antennal extract and antennal primary cell
      cultures, followed by molecular cloning. The complete cDNA sequence (1540 bp)
      contains an open reading frame encoding a protein of 353 amino acids. This
      deduced sequence possesses all of the characteristics of the Gq family and shares
      a very high degree of amino-acid sequence identity with vertebrate (80% with
      mouse or human Gqalpha) and invertebrate subunits (varying between 60 and 87% for
      Gqalpha from organisms as diverse as sponge and Drosophila). The expression
      pattern of the Gq subunit in adult antennae was associated with the olfactory
      sensilla suggesting a specific role in olfaction. These data provide molecular
      evidence for a component of the phosphoinositide signaling pathway in moth
      antennae: this G protein alpha subunit may be involved in the olfaction
      transduction process through interaction with G-protein-coupled receptors,
      stimulating the phospholipase C mediated second messenger pathway.

PMID- 11985592
TI  - The phosphotransferase system of Streptomyces coelicolor.
AB  - We have investigated the crr gene of Streptomyces coelicolor that encodes a
      homologue of enzyme IIAGlucose of Escherichia coli, which, as a component of the
      phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) plays a key
      role in carbon regulation by triggering glucose transport, carbon catabolite
      repression, and inducer exclusion. As in E. coli, the crr gene of S. coelicolor
      is genetically associated with the ptsI gene that encodes the general
      phosphotransferase enzyme I. The gene product IIACrr was overproduced, purified,
      and polyclonal antibodies were obtained. Western blot analysis revealed that
      IIACrr is expressed in vivo. The functionality of IIACrr was demonstrated by
      phosphoenolpyruvate-dependent phosphorylation via enzyme I and the histidine
      containing phosphoryl carrier protein HPr. Phosphorylation was abolished when
      His72, which corresponds to the catalytic histidine of E. coli IIAGlucose, was
      mutated. The capacity of IIACrr to operate in sugar transport was shown by
      complementation of the E. coli glucose-PTS. The striking functional resemblance
      between IIACrr and IIAGlucose was further demonstrated by its ability to confer
      inducer exclusion of maltose to E. coli. A specific interaction of IIACrr with
      the maltose permease subunit MalK from Salmonella typhimurium was uncovered by
      surface plasmon resonance. These data suggest that this IIAGlucose-like protein
      may be involved in carbon metabolism in S. coelicolor.

PMID- 11985593
TI  - Nuclear proteins that bind to metal response element a (MREa) in the Wilson
      disease gene promoter are Ku autoantigens and the Ku-80 subunit is necessary for
      basal transcription of the WD gene.
AB  - Wilson disease (WD), an inherited disorder affecting copper metabolism, is
      characterized by hepatic cirrhosis and neuronal degeneration, which result from
      toxic levels of copper that accumulate in the liver and brain, respectively. We
      reported previously that the approximately 1.3-kb promoter of the WD gene
      contains four metal response elements (MREs). Among the four MREs, MREa plays the
      most important role in the transcriptional activation of the WD promoter.
      Electrophoretic mobility shift assays (EMSAs) using synthetic MREa and an
      oligonucleotide containing the binding site for transcription factor Sp1 revealed
      the presence of nuclear factors that bind specifically to MREa. Two MREa-binding
      proteins of 70 and 82 kDa were purified using avidin-biotin affinity
      chromatography. Amino acid sequences of peptides from each protein were found to
      be highly homologous to the Ku proteins. Immunoblot analysis and EMSAs showed
      that the MREa-binding proteins are immunologically related to the Ku proteins. To
      study further the functional significance of these Ku-related proteins in
      transcriptional regulation of the WD gene, we performed RNA interference (RNAi)
      assays using a Ku-80 inverted-repeat gene to inhibit expression of the Ku-80 gene
      in vivo. Results of the RNAi assays showed that expression of the Ku-80 protein
      was suppressed in transfected cells, which in turn led to the suppression of the
      WD gene. In addition, a truncated Ku-80 (DeltaKu-80) mutant inhibited WD promoter
      activity in HepG2 cells in a dominant-negative manner. We also found that WD
      promoter activity was decreased in Xrs5 cells, which, unlike the CHO-K1 cells,
      are defective in the Ku-80 protein. When Ku-80 cDNA was transfected into Xrs5 and
      CHO cells, WD promoter activity was recovered only in Xrs5 cells. Taken together,
      our findings suggest that the Ku-80 subunit is required for constitutive
      expression of the WD gene.

PMID- 11985594
TI  - Bromoperoxidase activity of vanadate-substituted acid phosphatases from Shigella
      flexneri and Salmonella enterica ser. typhimurium.
AB  - Vanadium haloperoxidases and the bacterial class A nonspecific acid phosphatases
      have a conserved active site. It is shown that vanadate-substituted recombinant
      acid phosphatase from Shigella flexneri (PhoN-Sf) and Salmonella enterica ser.
      typhimurium (PhoN-Se) in the presence of H2O2 are able to oxidize bromide to
      hypobromous acid. Vanadate is essential for this activity. The kinetic parameters
      for the artificial bromoperoxidases have been determined. The Km value for H2O2
      is about the same as that for the vanadium bromoperoxidases from the seaweed
      Ascophyllum nodosum. However, the Km value for Br- is about 10-20 times higher,
      and the turnover values of about 3.4 min-1 and 33 min-1 for PhoN-Sf and PhoN-Se,
      respectively, are much slower, than those of the native bromoperoxidase. Thus,
      despite the striking similarity in the active-site structures of the vanadium
      haloperoxidases and the acid phosphatase, the turnover frequency is low, and
      clearly the active site of acid phosphatases is not optimized for haloperoxidase
      activity. Like the native vanadium bromoperoxidase, the vanadate-substituted PhoN
      Sf and PhoN-Se catalyse the enantioselective sulfoxidation of thioanisole.

PMID- 11985595
TI  - Effect of adenosine 5'-[beta,gamma-imido]triphosphate on myosin head domain
      movements.
AB  - Conventional and saturation transfer electron paramagnetic resonance spectroscopy
      (EPR and ST EPR) was used to study the orientation of probe molecules in muscle
      fibers in different intermediate states of the ATP hydrolysis cycle. A separate
      procedure was used to obtain ST EPR spectra with precise phase settings even in
      the case of samples with low spectral intensity. Fibers prepared from rabbit
      psoas muscle were labeled with isothiocyanate spin labels at the reactive thiol
      sites of the catalytic domain of myosin. In comparison with rigor, a significant
      difference was detected in the orientation-dependence of spin labels in the ADP
      and adenosine 5'-[beta,gamma-imido]triphosphate (AdoPP[CH2]P) states, indicating
      changes in the internal dynamics and domain orientation of myosin. In the
      AdoPP[CH2]P state, approximately half of the myosin heads reflected the motional
      state of ADP-myosin, and the other half showed a different dynamic state with
      greater mobility.

PMID- 11985596
TI  - Activation of a covalent outer membrane phospholipase A dimer.
AB  - The activity of outer membrane phospholipase A (OMPLA) is regulated by reversible
      dimerization. However, native OMPLA reconstituted in phospholipid vesicles was
      found to be present as a dimer but nevertheless inactive. To investigate the
      importance of dimerization for control of OMPLA activity, a covalent OMPLA dimer
      was constructed and its properties were compared to native OMPLA both in a
      micellar detergent and after reconstitution in a phospholipid bilayer. Unlike
      native OMPLA, activity of the covalent OMPLA dimer was independent of type and
      concentration of detergent in micellar systems. In such systems, the covalent
      OMPLA dimer invariantly displayed high calcium affinity. In contrast, high
      calcium concentrations were required to activate a covalent OMPLA dimer when
      present in intact vesicles. Solubilization of the vesicles increased the affinity
      for calcium, suggesting that in an intact bilayer the dimer interface is not
      properly formed. This was supported by the observation that OMPLA variants having
      an impaired dimeric interface also lacked high affinity calcium binding. A
      covalent linkage was not able to restore high affinity calcium binding in these
      variants, demonstrating that a proper dimer interface is essential for optimal
      catalysis.

PMID- 11985597
TI  - Soluble guanylate cyclase is allosterically inhibited by direct interaction with
      2-substituted adenine nucleotides.
AB  - Nitric oxide (NO), the principal endogenous ligand for soluble guanylate cyclase
      (sGC), stimulates that enzyme and accumulation of intracellular cGMP, which
      mediates many of the (patho) physiological effects of NO. Previous studies
      demonstrated that 2-substituted adenine nucleotides, including 2-methylthioATP
      (2MeSATP) and 2-chloroATP (2ClATP), allosterically inhibit guanylate cyclase C,
      the membrane-bound receptor for the Escherichia coli heat-stable enterotoxin in
      the intestine. The present study examined the effects of 2-substituted adenine
      nucleotides on crude and purified sGC. 2-Substituted nucleotides inhibited basal
      and NO-activated crude and purified sGC, when Mg2+ served as the substrate cation
      cofactor. Similarly, 2-substituted adenine nucleotides inhibited those enzymes
      when Mn2+, which activates sGC in a ligand-independent fashion, served as the
      substrate cation cofactor. Inhibition of sGC by 2-substituted nucleotides was
      associated with a decrease in Vmax, consistent with a noncompetitive mechanism.
      In contrast to guanylate cyclase C, 2-substituted nucleotides inhibited sGC by a
      guanine nucleotide-independent mechanism. These studies demonstrate that 2
      substituted adenine nucleotides allosterically inhibit basal and ligand
      stimulated sGC. They support the suggestion that allosteric inhibition by adenine
      nucleotides is a general characteristic of the family of guanylate cyclases. This
      allosteric inhibition is mediated by direct interaction of adenine nucleotides
      with sGC, likely at the catalytic domain in a region outside the substrate
      binding site.

PMID- 11985598
TI  - Structural studies on the core and the O-polysaccharide repeating unit of
      Pseudomonas aeruginosa immunotype 1 lipopolysaccharide.
AB  - The structure of the lipopolysaccharide (LPS) of Pseudomonas aeruginosa
      immunotype 1 was studied after mild acid and strong alkaline degradations by MS
      and NMR spectroscopy. Three types of LPS molecules were found, including those
      with an unsubstituted glycoform 1 core (A) or an isomeric glycoform 2 core
      substituted with one O-polysaccharide repeating unit (B) or with a long-chain O
      polysaccharide. Therefore, of two core glycoforms, only glycoform 2 accepts the O
      polysaccharide. In the structures A and B, Kdo, Hep, Hep7Cm, GalNAcAN3Ac,
      GalNFoAN, QuiNAc, GalNAla represent 3-deoxy-d-manno-octulosonic acid, l-glycero-d
      manno-heptose, 7-O-carbamoyl-l-glycero-d-manno-heptose, 2-acetamido-3-O-acetyl-2
      deoxygalacturonamide, 2-formamido-2-deoxygalacturonamide, 2-acetamido-2,6
      dideoxyglucose and 2-(l-alanylamino)-2-deoxygalactose, respectively; all sugars
      are in the pyranose form and have the d configuration unless otherwise stated.
      One or more phosphorylation sites may be occupied by diphosphate groups. In a
      minority of the LPS molecules, an O-acetyl group is present in the outer core
      region at unknown position. The site and the configuration of the linkage between
      the O-polysaccharide and the core and the structure of the O-polysaccharide
      repeating unit were defined in P. aeruginosa immunotype 1. The QuiNAc residue
      linked to the Rha residue of the core was found to have the beta configuration,
      whereas in the interior repeating units of the O-polysaccharide this residue is
      in the alpha-configuration. The data obtained are in accordance with the
      initiation of biosynthesis of the O-polysaccharide of P. aeruginosa O6, which is
      closely related to immunotype 1, by transfer of d-QuiNAc-1-P to undecaprenyl
      phosphate followed by synthesis of the repeating O-antigen tetrasaccharide.

PMID- 11985599
TI  - Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a
      biosynthetic key to over 2000 monoterpenoid indole alkaloids.
AB  - Strictosidine glucosidase (SG) is an enzyme that catalyses the second step in the
      biosynthesis of various classes of monoterpenoid indole alkaloids. Based on the
      comparison of cDNA sequences of SG from Catharanthus roseus and raucaffricine
      glucosidase (RG) from Rauvolfia serpentina, primers for RT-PCR were designed and
      the cDNA encoding SG was cloned from R. serpentina cell suspension cultures. The
      active enzyme was expressed in Escherichia coli and purified to homogeneity.
      Analysis of its deduced amino-acid sequence assigned the SG from R. serpentina to
      family 1 of glycosyl hydrolases. In contrast to the SG from C. roseus, the enzyme
      from R. serpentina is predicted to lack an uncleavable N-terminal signal
      sequence, which is believed to direct proteins to the endoplasmic reticulum. The
      temperature and pH optimum, enzyme kinetic parameters and substrate specificity
      of the heterologously expressed SG were studied and compared to those of the C.
      roseus enzyme, revealing some differences between the two glucosidases. In vitro
      deglucosylation of strictosidine by R. serpentina SG proceeds by the same
      mechanism as has been shown for the C. roseus enzyme preparation. The reaction
      gives rise to the end product cathenamine and involves 4,21-dehydrocorynantheine
      aldehyde as an intermediate. The enzymatic hydrolysis of dolichantoside (Nbeta
      methylstrictosidine) leads to several products. One of them was identified as a
      new compound, 3-isocorreantine A. From the data it can be concluded that the
      divergence of the biosynthetic pathways leading to different classes of indole
      alkaloids formed in R. serpentina and C. roseus cell suspension cultures occurs
      at a later stage than strictosidine deglucosylation.

PMID- 11985600
TI  - Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice
      lacking the aromatase gene (Cyp19 ).
AB  - We previously generated mice lacking aromatase activity by targeted disruption of
      Cyp19 (ArKO mice), and reported phenotypes of the female mice, showing hemorrhage
      formation and follicular depletion in the ovary, diminution in uterine size, and
      bone loss. In the present study, we examined the influence of dietary bisphenol A
      (BPA), a monomer used for the production of polycarbonate and known to have
      estrogenic activity, on these phenotypes of the ArKO mice. When ArKO mice were
      fed chow diets supplemented with 0.1% or 1% (w/w) BPA for 5 months, they were
      protected from ovarian degeneration, uterine diminution and bone loss in a dose
      dependent manner. Northern blot analyses of ovarian RNA of ArKO mice showed
      differences in the expression levels of insulin-like growth factor (IGF)-I, IGF-I
      receptor, growth differentiation factor 9 and bone morphogenetic protein 15 as
      compared with those in the ovaries of wild-type mice. The differences in the
      expression levels were restored by dietary BPA. In the ArKO uteri, expression of
      progesterone receptor and vascular endothelial growth factor mRNAs was
      diminished, and was restored by BPA to the levels in wild-type mice. In contrast,
      BPA had little effect on the ovarian, uterine and skeletal structures of wild
      type mice. In conclusion, estrogenic effects of BPA on the reproductive tract as
      well as skeletal tissue were evident in adult female ArKO mice. These results
      suggest that the ArKO mouse is an animal model suitable for studying effects of
      estrogenic chemicals as well as estrogen in vivo.

PMID- 11985601
TI  - Secretion of egg envelope protein ZPC after C-terminal proteolytic processing in
      quail granulosa cells.
AB  - In avian species, an egg envelope homologous to the mammalian zona pellucida is
      called the perivitelline membrane. We have previously reported that one of its
      components, a glycoprotein homologous to mammalian ZPC, is synthesized in the
      granulosa cells of the quail ovary. In the present study, we investigated the
      proteolytic cleavage of the newly synthesized ZPC and the secretion of ZPC from
      the granulosa cells. Western blot analysis of the cell lysates demonstrated that
      the 43-kDa protein is the precursor of mature ZPC (proZPC), and is converted to
      the 35-kDa protein before secretion. The accumulation of proZPC in the presence
      of brefeldin A, and conversion of proZPC to ZPC in the presence of monensin,
      indicate the possibility that the proteolytic processing of ZPC occurs in the
      Golgi apparatus. An analysis of amino-acid sequence identified that the C
      terminus of mature ZPC protein is Phe360, and the N-terminal amino-acid sequence
      of the proZPC-derived fragment was determined as Asp363. These results suggest
      that newly synthesized ZPC is cleaved at the consensus furin cleavage site, and
      the resulting two basic residues at the C terminus are subsequently trimmed off
      to generate mature ZPC prior to secretion.

PMID- 11985602
TI  - Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge.
AB  - We report the isolation of a novel antimicrobial peptide, bass hepcidin, from the
      gill of hybrid striped bass, white bass (Morone chrysops) x striped bass (M.
      saxatilis). After the intraperitoneal injection of Micrococcus luteus and
      Escherichia coli, the peptide was purified from HPLC fractions with antimicrobial
      activity against Escherichia coli. Sequencing by Edman degradation revealed a 21
      residue peptide (GCRFCCNCCPNMSGCGVCCRF) with eight putative cysteines. Molecular
      mass measurements of the native peptide and the reduced and alkylated peptide
      confirmed the sequence with four intramolecular disulfide bridges. Peptide
      sequence homology to human hepcidin and other predicted hepcidins, indicated that
      the peptide is a new member of the hepcidin family. Nucleotide sequences for cDNA
      and genomic DNA were determined for white bass. A predicted prepropeptide (85
      amino acids) consists of three domains: a signal peptide (24 amino acids),
      prodomain (40 amino acids) and a mature peptide (21 amino acids). The gene has
      two introns and three exons. A TATA box and several consensus-binding motifs for
      transcription factors including C/EBP, nuclear factor-kappaB, and hepatocyte
      nuclear factor were found in the region upstream of the transcriptional start
      site. In white bass liver, hepcidin gene expression was induced 4500-fold
      following challenge with the fish pathogen, Streptococcus iniae, while expression
      levels remained low in all other tissues tested. A novel antimicrobial peptide
      from the gill, bass hepcidin, is predominantly expressed in the liver and highly
      inducible by bacterial exposure.

PMID- 11985603
TI  - The amyloid precursor protein interacts with neutral lipids.
AB  - The amyloid protein precursor (APP) was incorporated into liposomes or
      phospholipid monolayers. APP insertion into liposomes required neutral lipids,
      such as L-alpha-phosphatidylcholine, in the target membrane. It was prevented in
      vesicles containing L-alpha-phosphatidylserine. The insertion was enhanced in
      acidic solutions, suggesting that it is modulated by specific charge/charge
      interactions. Surface-active properties and behaviour of APP were characterized
      during insertion of the protein in monomolecular films of L-alpha
      phosphatidylcholine, L-alpha-phosphatidylethanolamine or L-alpha
      phosphatidylserine. The presence of the lipid film enhanced the rate of
      adsorption of the protein at the interface, and the increase in surface pressure
      was consistent with APP penetrating the lipid film. The adsorption of APP on the
      lipid monolayers displayed a significant head group dependency, suggesting that
      the changes in surface pressure produced by the protein were probably affected by
      electrostatic interactions with the lipid layers. Our results indicate that the
      penetration of the protein into the lipid monolayer is also influenced by the
      hydrophobic interactions between APP and the lipid. CD spectra showed that a
      large proportion of the alpha-helical secondary structure of APP remained
      preserved over the pH or ionic strength ranges used. Our findings suggest that
      APP/membrane interactions are mediated by the lipid composition and depend on
      both electrostatic and hydrophobic effects, and that the variations observed are
      not due to major secondary structural changes in APP. These observations may be
      related to the partitioning of APP into membrane microdomains.

PMID- 11985604
TI  - Expression of recombinant murine pregnancy-associated plasma protein-A (PAPP-A)
      and a novel variant (PAPP-Ai) with differential proteolytic activity.
AB  - Murine pregnancy-associated plasma protein-A (PAPP-A) cDNA encoding a 1545 amino
      acid protein has been cloned. We have also identified and cloned cDNA that
      encodes a novel variant of PAPP-A, PAPP-Ai, carrying a 29-residue highly basic
      insert. The point of insertion corresponds to a junction between two exons in the
      human PAPP-A gene. The human intron flanked by these exons does not encode a
      homologous corresponding insert, which is unique to the mouse. The overall
      sequence identity between murine and human PAPP-A is 91%, and murine PAPP-A
      contains sequence motifs previously described in the sequence of human PAPP-A.
      Through expression in mammalian cells, we show that murine PAPP-A and PAPP-Ai are
      active metalloproteinases, both capable of cleaving insulin-like growth factor
      binding protein (IGFBP)-4 and -5. Cleavage of IGFBP-4 is dramatically enhanced by
      the addition of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by IGF, as
      previously established with human PAPP-A. Surprisingly, however, quantitative
      analyses demonstrate that the murine PAPP-Ai cleaves IGFBP-4 very slowly compared
      to PAPP-A, even though its ability to cleave IGFBP-5 is unaffected by the
      presence of the insert. By RT-PCR analysis, we find that both variants are
      expressed in several tissues. The level of mRNA in the murine placenta does not
      exceed the levels of other tissues analyzed. Furthermore, the IGFBP-4-proteolytic
      activity of murine pregnancy serum is not elevated. This is in striking contrast
      to the increase seen in human pregnancy serum, and the expression of PAPP-A in
      the human placenta, which exceeds other tissues at least 250-fold. Interestingly,
      the position of the insert of PAPP-Ai, within the proteolytic domain, lies in
      close proximity to the cysteine residue, which in human PAPP-A forms a disulfide
      bond with the proform of eosinophil major basic protein (proMBP). ProMBP
      functions as a proteinase inhibitor in the PAPP-A-proMBP complex, but whether any
      mechanistic parallel on regulation of proteolytic activity can be drawn between
      the insert of PAPP-Ai and the linkage to proMBP is not known. Importantly, these
      data support the development of the mouse as a model organism for the study of
      PAPP-A, which must take into account the differences between the mouse and the
      human.

PMID- 11985605
TI  - Effect of coenzymes and thyroid hormones on the dual activities of Xenopus
      cytosolic thyroid-hormone-binding protein (xCTBP) with aldehyde dehydrogenase
      activity.
AB  - A cytosolic thyroid-hormone-binding protein (xCTBP), predominantly responsible
      for the major binding activity of T3 in the cytosol of Xenopus liver, has been
      shown to be identical to aldehyde dehydrogenase class 1 (ALDH1) [Yamauchi, K.,
      Nakajima, J., Hayashi, H., Horiuchi, R. & Tata, J.R. (1999) J. Biol. Chem. 274,
      8460-8469]. Within this paper we surveyed which signaling, and other, compounds
      affect the thyroid hormone binding activity and aldehyde dehydrogenase activity
      of recombinant Xenopus ALDH1 (xCTBP/xALDH1) while examining the relationship
      between these two activities. NAD+ and NADH (each 200 microm), and two steroids
      (20 microm), inhibit significantly the T3-binding activity, while NADH and NADPH
      (each 200 microm), and iodothyronines (1 microm), inhibit the ALDH activity.
      Scatchard analysis and kinetic studies of xCTBP/xALDH1 indicate that NAD+ and T3
      are noncompetitive inhibitors of thyroid-hormone-binding and ALDH activities,
      respectively. These results indicate the formation of a ternary complex
      consisting of the protein, NAD+ and thyroid hormone. Although the in vitro
      studies indicate that NAD+ and NADH markedly decrease T3-binding to xCTBP/xALDH1
      at approximately 10-4 m, a concentration equal to the NAD content in various
      Xenopus tissues, photoaffinity-labeling of [125I]T3 using cultured Xenopus cells
      demonstrates xCTBP/xALDH1 bound T3 within living cells. These results raise the
      possibility that an unknown factor(s) besides NAD+ and NADH may modulate the
      thyroid-hormone-binding activity of xCTBP/xALDH1. In comparison, thyroid hormone,
      at its physiological concentration, would poorly modulate the enzyme activity of
      xCTBP/xALDH1.

PMID- 11985606
TI  - Chromatin. The living genome.

PMID- 11985607
TI  - Chromatin assembly. Cooperation between histone chaperones and ATP-dependent
      nucleosome remodeling machines.
AB  - Chromatin is a highly dynamic structure that plays an essential role in
      regulating all nuclear processes that utilize the DNA template including DNA
      repair, replication, transcription and recombination. Thus, the mechanisms by
      which chromatin structures are assembled and modified are questions of broad
      interest. This minireview will focus on two groups of proteins: (a) histone
      chaperones and (b) ATP-dependent chromatin remodeling machines, that co-operate
      to assemble DNA and histone proteins into chromatin. The current understanding of
      how histone chaperones and ATP-dependent remodeling machines coordinately
      assemble chromatin in vitro will be discussed, together with the growing body of
      genetic evidence that supports the role of histone chaperones in the cell.

PMID- 11985608
TI  - Nuclear receptor-dependent transcription with chromatin. Is it all about enzymes?
AB  - Nuclear receptors (NRs) are ligand-regulated, DNA-binding transcription factors
      that function in the chromatin environment of the nucleus to alter the expression
      of subsets of hormone-responsive genes. It is clear that chromatin, rather than
      being a passive player, has a profound effect on both transcriptional repression
      and activation mediated by NRs. NRs act in conjunction with at least three
      general classes of cofactors to regulate transcription in the context of
      chromatin: (a) chromatin remodelers; (b) corepressors; and (c) coactivators, many
      of which have distinct enzymatic activities that remodel nucleosomes or
      covalently modify histones (e.g. acetylases, deacetylases, methyltransferases,
      and kinases). In this paper, we will present a brief overview of these enzymes,
      their activities, and how they assist NRs in the repression or activation of
      transcription in the context of chromatin.

PMID- 11985609
TI  - Chromatin remodeling in nuclear cloning.
AB  - Nuclear cloning is a procedure to create new animals by injecting somatic nuclei
      into unfertilized oocytes. Recent successes in mammalian cloning with
      differentiated adult nuclei strongly indicate that oocyte cytoplasm contains
      unidentified remarkable reprogramming activities with the capacity to erase the
      previous memory of cell differentiation. At the heart of this nuclear
      reprogramming lies chromatin remodeling as chromatin structure and function
      define cell differentiation through regulation of the transcriptional activities
      of the cells. Studies involving the modification of chromatin elements such as
      selective uptake or release of binding proteins, covalent histone modifications
      including acetylation and methylation, and DNA methylation should provide
      significant insight into the molecular mechanisms of nuclear dedifferentiation
      and redifferentiation in oocyte cytoplasm.

PMID- 11985610
TI  - Nucleotide excision repair and chromatin remodeling.
AB  - The organization of DNA within eukaryotic cell nuclei poses special problems and
      opportunities for the cell. For example, assembly of DNA into chromatin is
      thought to be a principle mechanism by which adventitious general transcription
      is repressed. However, access to genomic DNA for events such as DNA repair must
      be facilitated by energy-intensive processes that either directly alter chromatin
      structure or impart post-translational modifications, leading to increased DNA
      accessibility. The assembly of DNA into chromatin affects both the incidence of
      damage to DNA and repair of that damage. Correction of most damage to DNA caused
      by UV irradiation occurs via the nucleotide excision repair (NER) process. NER
      requires extensive involvement of large multiprotein complexes with relatively
      large stretches of DNA. Here, we review recent evidence suggesting that at least
      some steps of NER require ATP-dependent chromatin remodeling activities while
      perhaps others do not.

PMID- 11985611
TI  - When the embryonic genome flexes its muscles.
AB  - During the development of multicellular organisms, both transient and stable gene
      expression patterns have to be established in a precisely orchestrated sequence.
      Evidence from diverse model organisms indicates that this epigenetic program
      involves not only transcription factors, but also the local structure,
      composition, and modification of chromatin, which define and maintain the
      accessibility and transcriptional competence of the nucleosomal DNA template. A
      paradigm for the interdependence of development and chromatin is constituted by
      the mechanisms controlling the specification and differentiation of the skeletal
      muscle cell lineage in vertebrates, which is the topic of this review.

PMID- 11985612
TI  - Beyond the ABCs of CKC and SCC. Do centromeres orchestrate sister chromatid
      cohesion or vice versa?
AB  - The centromere-kinetochore complex is a highly specialized chromatin domain that
      both mediates and monitors chromosome-spindle interactions responsible for
      accurate partitioning of sister chromatids to daughter cells. Centromeres are
      distinguished from adjacent chromatin by specific patterns of histone
      modification and the presence of a centromere-specific histone H3 variant (e.g.
      CENP-A). Centromere-proximal regions usually correspond to sites of avid and
      persistent sister chromatid cohesion mediated by the conserved cohesin complex.
      In budding yeast, there is a substantial body of evidence indicating centromeres
      direct formation and/or stabilization of centromere-proximal cohesion. In other
      organisms, the dependency of cohesion on centromere function is not as clear.
      Indeed, it appears that pericentromeric heterochromatin recruits cohesion
      proteins independent of centromere function. Nonetheless, aspects of centromere
      function are impaired in the absence of sister chromatid cohesion, suggesting the
      two are interdependent. Here we review the nature of centromeric chromatin, the
      dynamics and regulation of sister chromatid cohesion, and the relationship
      between the two.

PMID- 11985613
TI  - A pool of Y2 neuropeptide Y receptors activated by modifiers of membrane
      sulfhydryl or cholesterol balance.
AB  - The cloned guinea-pig Y2 neuropeptide Y (NPY) receptors expressed in Chinese
      hamster ovary (CHO) cells, as well as the Y2 receptors natively expressed in rat
      forebrain, are distributed in two populations. A smaller population that is
      readily accessed by agonist peptides on the surface of intact cells constitutes
      less than 30% of Y2 receptors detected in particulates after cell homogenization.
      A much larger fraction of cell surface Y2 sites can be activated by sulfhydryl
      modifiers. A fast and large activation of these masked or cryptic sites could be
      obtained with membrane-permeating, vicinal cysteine-bridging arsenical
      phenylarsine oxide. A lower activation is effected by N-ethylmaleimide, an
      alkylator that slowly penetrates lipid bilayers. The restricted-access alkylator,
      2-[(trimethylammonium)ethyl]methanethiosulfonate, was not effective in unmasking
      these sites. Some of the hidden cell surface Y2 sites could be activated by
      polyene filipin III through complexing of membrane cholesterol. The results are
      consistent with the presence of a large Y2 reserve in a compartment that can be
      accessed by alteration of sulfhydryl balance or fluidity of the cell membrane,
      and by treatments that affect the anchoring and aggregation of membrane proteins.

PMID- 11985614
TI  - Chimeric receptor analyses of the interactions of the ectodomains of ErbB-1 with
      epidermal growth factor and of those of ErbB-4 with neuregulin.
AB  - A series of chimeric receptors was generated between the epidermal growth factor
      (EGF) receptor, ErbB-1, and its homologue, ErbB-4, to investigate the roles of
      the extracellular domains (I-IV) in the ligand specificities. As compared with
      ErbB-1 and the chimeras with both domains I and III of ErbB-1, the chimeras with
      only one of these domains exhibited reduced binding of 125I-labeled EGF.
      Particularly, the contribution of domain III was appreciably larger than that of
      domain I of ErbB-1 in 125I-labeled EGF binding. Nevertheless, the chimeras with
      domain III of ErbB-1 and domain I of ErbB-4 were prevented from binding to 125I
      labeled EGF competitively by the ErbB-4 ligand, neuregulin (NRG). On the other
      hand, NRG did not compete with 125I-labeled EGF for binding to the chimeras with
      the ErbB-1 domain I and the ErbB-4 domain III. Therefore, NRG binding to ErbB-4
      depends much more on domain I than on domain III. With respect to
      autophosphorylation and subsequent ERK activation, EGF activated the chimeras
      with either domain I or III of ErbB-1. In contrast, NRG activated the chimeras
      with the ErbB-4 domain I and the ErbB-1 domain III, but not those with the ErbB-1
      domain I and the ErbB-4 domain III. Therefore, the relative contributions between
      domains I and III of ErbB-4 in the NRG signaling are different from those of ErbB
      1 in the EGF signaling.

PMID- 11985615
TI  - Exploring the role of a glycine cluster in cold adaptation of an alkaline
      phosphatase.
AB  - In an effort to explore the role of glycine clusters on the cold adaptation of
      enzymes, we designed point mutations aiming to alter the distribution of glycine
      residues close to the active site of the psychrophilic alkaline phosphatase from
      the Antarctic strain TAB5. The mutagenesis targets were residues Gly261 and
      Gly262. The replacement of Gly262 by Ala resulted in an inactive enzyme.
      Substitution of Gly261 by Ala resulted to an enzyme with lower stability and
      increased energy of activation. The double mutant G261A/Y269A designed on the
      basis of side-chain packing criteria from a modelled structure of the enzyme
      resulted in restoration of the energy of activation to the levels of the native
      enzyme and in an increased stability compared to the mutant G261A. It seems
      therefore, that the Gly cluster in combination with its structural environment
      plays a significant role in the cold adaptation of the enzyme.

PMID- 11985616
TI  - The effects of low pH on the properties of protochlorophyllide oxidoreductase and
      the organization of prolamellar bodies of maize (Zea mays).
AB  - Prolamellar bodies (PLB) contain two photochemically active forms of the enzyme
      protochlorophyllide oxidoreductase POR-PChlide640 and POR-PChlide650 (the
      spectral forms of POR-Chlide complexes with absorption maxima at the indicated
      wavelengths). Resuspension of maize PLB in media with a pH below 6.8 leads to a
      rapid conversion of POR-PChlide650 to POR-PChlide640 and a dramatic re
      organization of the PLB membrane system. In the absence of excess NADPH, the
      absorption maximum of the POR complex undergoes a further shift to about 635 nm.
      This latter shift is reversible on the re-addition of NADPH with a half
      saturation value of about 0.25 mm NADPH for POR-PChlide640 reformation. The
      disappearance of POR-PChlide650 and the reorganization of the PLB, however, are
      irreversible. Restoration of low-pH treated PLB to pH 7.5 leads to a further
      breakdown down of the PLB membrane and no reformation of POR-PChlide650. Related
      spectral changes are seen in PLB aged at room temperature at pH 7.5 in NADPH-free
      assay medium. The reformation of POR-PChlide650 in this system is readily
      reversible on re-addition of NADPH with a half-saturation value about 1.0 microm.
      Comparison of the two sets of changes suggest a close link between the stability
      of the POR-PChlide650, membrane organization and NADPH binding. The low-pH driven
      spectral changes seen in maize PLB are shown to be accelerated by adenosine AMP,
      ADP and ATP. The significance of this is discussed in terms of current
      suggestions of the possible involvement of phosphorylation (or adenylation) in
      changes in the aggregational state of the POR complex.

PMID- 11985617
TI  - Phosphatidylinositol synthesis and exchange of the inositol head are catalysed by
      the single phosphatidylinositol synthase 1 from Arabidopsis.
AB  - In order to study some of its enzymatic properties, phosphatidylinositol synthase
      1 (AtPIS1) from the plant Arabidopsis thaliana was expressed in Escherichia coli,
      a host naturally devoid of phosphatidylinositol (PtdIns). In the context of the
      bacterial membrane and in addition to de novo synthesis, the plant enzyme is
      capable of catalysing the exchange of the inositol polar head for another
      inositol. Our data clearly show that the CDP-diacylglycerol-independent exchange
      reaction can occur using endogenous PtdIns molecular species or PtdIns molecular
      species from soybean added exogenously. Exchange has been observed in the absence
      of cytidine monophosphate (CMP), but is greatly enhanced in the presence of 4
      microm CMP. Our data also show that AtPIS1 catalyses the removal of the polar
      head in the presence of much higher concentrations of CMP, in a manner that
      suggests a reverse of synthesis. All of the PtdIns metabolizing activities
      require free manganese ions. EDTA, in the presence of low Mn2+ concentrations,
      also has an enhancing effect.

PMID- 11985618
TI  - Role of sulfoquinovosyl diacylglycerol for the maintenance of photosystem II in
      Chlamydomonas reinhardtii.
AB  - The physiological role of sulfoquinovosyl diacylglycerol (SQDG) in photosynthesis
      was investigated with a SQDG defective mutant (hf-2) of Chlamydomonas reinhardtii
      that did not have any detectable amount of SQDG. The mutant showed a lower rate
      of photosystem II (PSII) activity by approximately 40% and also a lower growth
      rate than those of the wild-type. Results of genetical analysis of hf-2 strongly
      suggest that the SQDG defect and the lowered PSII activity are due to a single
      gene mutation. The supplementation of SQDG to hf-2 cells restored the lowered
      PSII activity to the same level as that of wild-type cells, and also enabled the
      mutant to grow even in the presence of 135 nm 3-(3,4-dichlorophenyl)-1,1
      dimethylurea. Moreover, the incubation of isolated thylakoid membranes of hf-2
      with SQDG raised the lowered PSII activity. Chemical modifications of SQDG
      impaired the recovery of PSII activity. The results suggest that SQDG is
      indispensable for PSII activity in Chlamydomonas by maintaining PSII complexes in
      their proper state.

PMID- 11985619
TI  - Molecular and biochemical characteristics of a gene encoding an alcohol acyl
      transferase involved in the generation of aroma volatile esters during melon
      ripening.
AB  - Two genes (CM-AAT1 and CM-AAT2) with strong sequence homology (87% identity at
      the protein level) putatively involved in the formation of aroma volatile esters
      have been isolated from Charentais melon fruit. They belong to a large and highly
      divergent family of multifunctional plant acyl-transferases and show at most 21%
      identity to the only other fruit acyl-transferase characterized so far in
      strawberry. RT-PCR studies indicated that both genes were specifically expressed
      in fruit at increasing rates in the early and mid phases of ripening. Expression
      was severely reduced in ethylene-suppressed antisense ACC oxidase (AS) fruit and
      in wild-type (WT) fruit treated with the ethylene antagonist 1-MCP. Cloning of
      the two genes in yeast revealed that the CM-AAT1 protein exhibited alcohol acyl
      transferase activity while no such activity could be detected for CM-AAT2 despite
      the strong homology between the two sequences. CM-AAT1 was capable of producing
      esters from a wide range of combinations of alcohols and acyl-CoAs. The higher
      the carbon chain of aliphatic alcohols, the higher the activity. Branched
      alcohols were esterified at differential rates depending on the position of the
      methyl group and the nature of the acyl donor. Phenyl and benzoyl alcohols were
      also good substrates, but activity varied with the position and size of the
      aromatic residue. The cis/trans configuration influenced activity either
      positively (2-hexenol) or negatively (3-hexenol). Because ripening melons evolve
      the whole range of esters generated by the recombinant CM-AAT1 protein, we
      conclude that CM-AAT1 plays a major role in aroma volatiles formation in the
      melon.

PMID- 11985620
TI  - Enhancement by alpha-tocopheryl hemisuccinate of nitric oxide production induced
      by lypopolysaccharide and interferon-gamma through the upregulation of protein
      kinase C in rat vascular smooth muscle cells.
AB  - The effect of alpha-tocopheryl hemisuccinate (TS) on lipopolysaccharide
      (LPS)/interferon-gamma (IFN)-induced nitric oxide production in rat vascular
      smooth muscle cells (VSMC) was examined. The LPS/IFN-induced NO production was
      enhanced by TS but not by the other alpha-tocopherol (alpha-T) derivatives alpha
      tocopheryl acetate (TA) and alpha-tocopheryl nicotinate (TN), or alpha-T itself.
      alpha-T, TA and TN inhibited the enhancement by TS of LPS/IFN-induced NO
      production. The enhancing effect of TS was observed in the presence of LPS, but
      not IFN, suggesting that TS participates in the LPS-stimulated signal pathway
      leading to NO production. Protein kinase C (PKC) inhibitors, but not protein
      kinase A inhibitors, inhibited the enhancing effect of TS on LPS/IFN-induced NO
      production. Furthermore, TS enhanced the amount of PKCalpha in VSMC. From these
      results, we concluded that the enhancing effect of LPS/IFN-induced NO production
      was caused by upregulation of PKC in VSMC.

PMID- 11985621
TI  - Purification, characterization, cloning, and expression of the chicken liver ecto
      ATP-diphosphohydrolase.
AB  - We previously demonstrated that the major ecto-nucleoside triphosphate
      phosphohydrolase in the chicken liver membranes is an ecto-ATP-diphosphohydrolase
      (ecto- ATPDase) [Caldwell, C., Davis, M.D. & Knowles, A.F. (1999) Arch. Biochem.
      Biophys. 362, 46-58]. Enzymatic properties of the liver membrane ecto-ATPDase are
      similar to those of the chicken oviduct ecto-ATPDase that we have previously
      purified and cloned. Using antibody developed against the latter, we have
      purified the chicken liver ecto-ATPDase to homogeneity. The purified enzyme is a
      glycoprotein with a molecular mass of 85 kDa and a specific activity of
      approximately 1000 U.mg protein-1. Although slightly larger than the 80-kDa
      oviduct enzyme, the two ecto-ATPDases are nearly identical with respect to their
      enzymatic properties and mass of the deglycosylated proteins. The primary
      sequence of the liver ecto-ATPDase deduced from its cDNA obtained by RT-PCR
      cloning also shows only minor differences from that of the oviduct ecto-ATPDase.
      Immunochemical staining demonstrates the distribution of the ecto-ATPDase in the
      bile canaliculi of the chicken liver. HeLa cells transfected with the chicken
      liver ecto-ATPDase cDNA express an ecto-nucleotidase activity with
      characteristics similar to the enzyme in its native membranes, most significant
      of these is stimulation of the ATPDase activity by detergents, which inhibits
      other members of the ecto- nucleoside triphosphate diphosphohydrolase (E-NTPDase)
      family. The stimulation of the expressed liver ecto-ATPDase by detergents
      indicates that this property is intrinsic to the enzyme protein, and cannot be
      attributed to the lipid environment of the native membranes. The molecular
      identification and expression of a liver ecto-ATPDase, reported here for the
      first time, will facilitate future investigations into the differences between
      structure and function of the different E-NTPDases, existence of liver ecto
      ATPDase isoforms in different species, its alteration in pathogenic conditions,
      and its physiological function.

PMID- 11985622
TI  - Re-oxygenation of hypoxic simian virus 40 (SV40)-infected CV1 cells causes
      distinct changes of SV40 minichromosome-associated replication proteins.
AB  - Hypoxia interrupts the initiation of simian virus 40 (SV40) replication in vivo
      at a stage situated before unwinding of the origin region. After re-oxygenation,
      unwinding followed by a synchronous round of viral replication takes place. To
      further characterize the hypoxia-induced inhibition of unwinding, we analysed the
      binding of several replication proteins to the viral minichromosome before and
      after re-oxygenation. T antigen, the 34-kDa subunit of replication protein A
      (RPA), topoisomerase I, the 48-kDa subunit of primase, the 125-kDa subunit of
      polymerase delta, and the 37-kDa subunit of replication factor C (RFC) were
      present at the viral chromatin already under hypoxia. The 70-kDa subunit of RPA,
      the 180-kDa subunit of polymerase alpha, and proliferating cell nuclear antigen
      (PCNA) were barely detectable at the SV40 chromatin under hypoxia and
      significantly increased after re-oxygenation. Immunoprecipitation of
      minichromosomes with T antigen-specific antibody and subsequent digestion with
      micrococcus nuclease revealed that most of the minichromosome-bound T antigen was
      associated with the viral origin in hypoxic and in re-oxygenated cells. T antigen
      catalysed unwinding of the SV40 origin occurred, however, only after re
      oxygenation as indicated by (a) increased sensitivity of re-oxygenated
      minichromosomes against digestion with single-stranded DNA-specific nuclease P1;
      (b) stabilization of RPA-34 binding at the SV40 minichromosome; and (c)
      additional phosphorylations of RPA-34 after re-oxygenation, probably catalysed by
      DNA-dependent protein kinase. The results presented suggest that the subunits of
      the proteins necessary for unwinding, primer synthesis and primer elongation
      first assemble at the SV40 origin in form of stable, active complexes directly
      before they start to work.

PMID- 11985623
TI  - Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled
      with in situ regeneration of NADH.
AB  - Phenylacetaldehyde reductase (PAR) produced by styrene-assimilating
      Corynebacterium strain ST-10 was used to synthesize chiral alcohols. This enzyme
      with a broad substrate range reduced various prochiral aromatic ketones and beta
      ketoesters to yield optically active secondary alcohols with an enantiomeric
      purity of more than 98% enantiomeric excess (e.e.). The Escherichia coli
      recombinant cells which expressed the par gene could efficiently produce
      important pharmaceutical intermediates; (R)-2-chloro-1-(3-chlorophenyl)ethanol
      (28 mg.mL-1) from m-chlorophenacyl chloride, ethyl (R)-4-chloro-3-hydroxy
      butanoate) (28 mg.mL-1) from ethyl 4-chloro-3-oxobutanoate and (S)-N-tert
      butoxycarbonyl(Boc)-3-pyrrolidinol from N-Boc-3-pyrrolidinone (51 mg.mL-1), with
      more than 86% yields. The high yields were due to the fact that PAR could
      concomitantly reproduce NADH in the presence of 3-7% (v/v) 2-propanol in the
      reaction mixture. This biocatalytic process provided one of the best asymmetric
      reductions ever reported.

PMID- 11985624
TI  - Systematic search for zinc-binding proteins in Escherichia coli.
AB  - A systematic search for Escherichia coli proteins with the zinc-binding activity
      was performed using the assay of radioactive Zn(II) binding to total E. coli
      proteins fractionated by two methods of two-dimensional gel electrophoresis. A
      total of 30-40 radioactive spots were identified, of which 14 have been assigned
      from N-terminal sequencing. In addition to five known zinc-binding proteins, nine
      zinc-binding proteins were newly identified including: acetate kinase (AckA),
      DnaK, serine hydroxymethyltransferase (GlyA), transketolase isozymes (TktA/TktB),
      translation elongation factor Ts (Tsf), ribosomal proteins L2 (RplB), L13 (RplM)
      and one of S15 (RpsO), S16 (RpsP) or S17 (RpsQ). Together with about 20 known
      zinc-binding proteins, the total number of zinc-binding proteins in E. coli
      increased up to more than 30 species (or more than 3% of about 1000 proteins
      expressed under laboratory culture conditions). The specificity and affinity of
      zinc-binding were analysed for some of the zinc-binding proteins.

PMID- 11985625
TI  - Two GPX-like proteins from Lycopersicon esculentum and Helianthus annuus are
      antioxidant enzymes with phospholipid hydroperoxide glutathione peroxidase and
      thioredoxin peroxidase activities.
AB  - This study investigated the enzymatic function of two putative plant GPXs, GPXle1
      from Lycopersicon esculentum and GPXha2 from Helianthus annuus, which show
      sequence identities with the mammalian phospholipid hydroperoxide glutathione
      peroxidase (PHGPX). Both purified recombinant proteins expressed in Escherichia
      coli show PHGPX activity by reducing alkyl, fatty acid and phospholipid
      hydroperoxides but not hydrogen peroxide in the presence of glutathione.
      Interestingly, both recombinant GPXle1 and GPXha2 proteins also reduce alkyl,
      fatty acid and phospholipid hydroperoxides as well as hydrogen peroxide using
      thioredoxin as reducing substrate. Moreover, thioredoxin peroxidase (TPX)
      activities were found to be higher than PHGPX activities in terms of efficiency
      and substrate affinities, as revealed by their respective Vmax and Km values. We
      therefore conclude that these two plant GPX-like proteins are antioxidant enzymes
      showing PHGPX and TPX activities.

PMID- 11985626
TI  - The symptomatic treatment of multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined
      aetiology that occurs sporadically and manifests itself as a combination of
      parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any
      effective therapy to reverse this condition, some of the symptoms may be, at
      least temporarily, improved with adequate symptomatic therapies. Medical
      treatment is largely aimed at mitigating the parkinsonian and autonomic features.
      The therapeutic results of levodopa therapy in cases of MSA are difficult to
      interpret because of their variability. Nevertheless, the statement that patients
      with MSA are non or poorly levodopa-responsive is misleading. Clinical and
      pathologically proven series document about 40-60% levodopa efficacy in patients
      with MSA presenting with predominant parkinsonian features. Unfortunately, other
      antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective
      than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's
      history and subsequently documented in the clinic by measuring lying and standing
      blood pressure. The diagnosis ideally should be confirmed in the laboratory with
      additional tests to determine the cause and evaluate the functional deficit, so
      as to aid treatment. A variety of pharmacological agents with different
      mechanisms of action have been used in MSA to reduce OH when this is symptomatic.
      OH can also be alleviated by avoiding aggravating factors, such as the effects of
      food, micturition, exposure to a warm environment and physiological diurnal
      changes and by using other non-pharmacological strategies. The treatment of the
      very common genito-urinary symptoms (incontinence, retention, impotence) should
      also be considered in order to improve the quality of life of these patients.

PMID- 11985627
TI  - The position of the neurologist in neuro-oncology.
AB  - Neuro-oncology is a growing new subspeciality with a strong interdisciplinary
      character. This position paper explains the role of neurology in the
      multidisciplinary field of neurosurgeons, radiotherapists and general
      oncologists, dealing with neuro-oncological patients. The paper delineates the
      varied spectrum of the field of neuro-oncology which expands from primary brain
      tumours, to metastatic and non-metastatic effects of systemic cancer on the
      central and peripheral nervous system, neurotoxicity due to cancer treatment and
      issues of quality of life. It has been written by the scientific neuro-oncology
      panel of the European Federation of Neurological Societies (EFNS) to delineate
      the situation of neuro-oncology in Europe, and facilitate the understanding and
      implementation of this subspeciality in the future.

PMID- 11985628
TI  - EFNS guideline on mild traumatic brain injury: report of an EFNS task force.
AB  - In 1999, a Task Force on Mild Traumatic Brain Injury (MTBI) was set up under the
      auspices of the European Federation of Neurological Societies. Its aim was to
      propose an acceptable uniform nomenclature for MTBI and definition of MTBI, and
      to develop a set of rules to guide initial management with respect to ancillary
      investigations, hospital admission, observation and follow-up.

PMID- 11985629
TI  - Serum uric acid levels in multiple sclerosis patients correlate with activity of
      disease and blood-brain barrier dysfunction.
AB  - Several findings suggest lower levels of serum uric acid in multiple sclerosis
      (MS) patients. The aim of this study is to investigate relationships of uric acid
      serum levels in relapse-remitting (RR) MS patients with clinical activity of
      disease and blood-brain barrier (BBB) condition. Sixty-three definite RRMS
      patients and 40 controls divided into two groups: 20 healthy donors and 20
      patients with other inflammatory neurological diseases (OINDs) were analysed. By
      using a quantitative enzymatic assay according to the manufacture's protocol and
      a commercial uric acid standard solution, serum uric acid levels were measured
      and the results were standardized. To investigate BBB function, magnetic
      resonance imaging after administration of gadolinium was used. MS patients were
      found to have significantly lower serum uric acid levels (193.89 +/- 49.05
      micromol/l; mean value +/-SD) in comparison with healthy donors (292.7 +/- 58.65
      micromol/l; P=0.000) and OIND patients (242.7 +/- 46.66 micromol/l; P=0.001). We
      found that MS patients with relapse had significantly lower serum uric acid
      levels (161.49 +/- 23.61 micromol/l) than MS patients with remission (234.39 +/-
      41.96 micromol/l; P=0.000) and more over, MS patients with BBB disruption had
      significantly lower serum uric acid levels (163.95 +/- 26.07 micromol/l) than
      those with normal BBB (252.48 +/- 25.94 micromol/l; P=0.000). Further, we also
      found that serum uric acid level independently correlated with disease activity,
      BBB disruption, and gender. These results indicate that lower uric acid levels in
      MS patients are associated with relapse and suggest that uric acid might be
      beneficial in the treatment of MS.

PMID- 11985630
TI  - Median nerve somatosensory evoked potentials in migraine.
AB  - In visual evoked potential studies, habituation during stimulus repetition with
      the same stimulus at a constant intensity has been found to be abnormal in
      migraineurs between attacks. The purpose of this study was to investigate
      habituation of somatosensory evoked potentials (SEPs) and the effects of migraine
      on them. Eighty-five subjects were included in the study: 30 healthy volunteers
      (HVs) and 55 migraineurs [30 with migraine without aura (MO), 25 with migraine
      with aura (MA)]. During continuous stimulation at 3 Hz, four blocks of 100
      responses were sequentially averaged of Erb's point (N9), cervical (N13), and
      cortical (N20) median nerve SEPs. Mean amplitude changes in the second, third and
      fourth blocks are expressed as percentages of the first block. There was
      habituation to N13 and N20 in the second, third and fourth blocks in HVs. In the
      migraine groups, there was no habituation; on the contrary, potentiation was
      found. This potentiation was statistically significant only in the second blocks
      for N13 (MO P=0.007, MA P=0.01 versus HVs). However, in both migraineur groups,
      the rate of N20 potentiations was statistically significant versus that in HVs
      for all blocks (all P < 0.05). It is concluded that whilst physiological
      habituation occurs in HVs for cervical and cortical SEPs, in migraine patients
      there is an interictal deficit of habituation of this sensory modality.

PMID- 11985631
TI  - Education, occupation, and perception of health amongst previous polio patients
      compared to their siblings.
AB  - Patients with previous polio represent a challenge for neurological
      rehabilitation. We examined 168 previous polio patients and 239 of their
      siblings, the patients either from the 1950-1954 epidemic cohort, or from a
      cohort of hospital-admitted rehabilitation patients. Ninety-four paralytic
      patients and 74 non-paralytic patients were included. All patients and siblings
      answered the same questionnaires for socioeconomic and health factors and chi
      square comparisons were performed. Previous polio did not affect the level of
      education. Both patients and siblings rated their educational options to have
      been good. Significantly less patients were full-time employed at the age of 40
      years compared to their siblings (P=0.015). This was the result of a lower full
      time employment rate amongst the paralytic patients, only 52% of this group being
      employed full-time. Male patients and paralytic patients reported to have
      experienced reduced professional options. More patients were living alone
      compared to their siblings (P=0.035). The perception of general health was lower
      amongst patients than siblings, as was assessment of total life situation and
      patients reported more frequently symptoms like pain and tiredness. In
      conclusion, previous polio had not lowered the polio patients' educational
      status, but fewer patients were employed full-time at the age of 40 years.

PMID- 11985632
TI  - Multiple MAG peptides are recognized by circulating T and B lymphocytes in
      polyneuropathy and multiple sclerosis.
AB  - Abnormal immune responses to myelin associated glycoprotein (MAG), a component of
      myelin of the central and peripheral nervous system, have been suggested to play
      a role in the pathogenesis of multiple sclerosis (MS) and certain types of
      inflammatory polyneuropathy. To identify possible immunodominant MAG peptides in
      neuroinflammation, we examined T and B cell responses to five selected synthetic
      MAG peptides and myelin proteins in 21 patients with non-inflammatory
      polyneuropathy, 26 patients with MS, 10 optic neuritis patients and 17 healthy
      subjects. Enzyme-linked immunosorbent spot-forming cell assays were adopted,
      allowing the detection and enumeration of individual antigen responsive T and B
      cells in body fluids. Patients with polyneuropathy as well as those with MS had
      elevated levels of T and B cells recognizing MAG and its peptides. Any of the
      five MAG peptides under study functioned as immunodominant T and/or B cell
      epitope in individual subjects. None of the MAG peptides elicited a specific
      disease-associated T or B cell response. The enhanced T and B cell response to
      myelin components like MAG may play some role in initiation and/or progression of
      these diseases, but they could also represent secondary responses associated with
      myelin damage and indicate tolerization rather than autoaggressive immunity.

PMID- 11985633
TI  - Ropinirole for the treatment of tremor in early Parkinson's disease.
AB  - The effect of Ropinirole on tremor in early Parkinson's disease (PD) was
      assessed. The results of three multicentre, randomized, double-blind trials
      comparing ropinirole monotherapy with levodopa, bromocriptine and placebo
      treatment were analysed retrospectively with respect to improvement of resting
      tremor and postural/action tremor as measured by items 20 and 21 of the motor
      section of the Unified Parkinson's Disease Rating Scale (UPDRS). Improvements in
      resting tremor were significantly better with ropinirole than placebo. There were
      no significant differences between the effect of ropinirole and those of levodopa
      (L-dopa) or bromocriptine on resting tremor. Postural/action tremor was mild in
      these early therapy studies, and there were no significant differences between
      treatment groups. These results suggest that ropinirole monotherapy is effective
      in treating resting tremor in early PD. On the other hand, response of
      postural/action tremor to dopaminergic treatment in early PD was not
      significantly better than to placebo at the dosages used in these trials.

PMID- 11985634
TI  - Electrophysiological study of vocal-fold mobility disorders using a magnetic
      stimulator.
AB  - In the field of neurolaryngology, there has been a great interest in
      neurophysiological studies, such as neurography, for the assessment of the
      integrity of the laryngeal neural pathway. Such tools provide an indication about
      the site and the nature of the nerve lesion. We have tried to use a magnetically
      evoked potential to assess the corticolaryngeal pathway in order to provide
      normative data on laryngeal nerve conductivity and to evaluate the integrity of
      the laryngeal neural system in patients with vocal-fold mobility disorders. This
      study was conducted on 26 subjects (10 normal volunteers and 16 patients with
      vocal-fold immobility) who were primarily selected on the basis of a
      comprehensive laryngeal evaluation including laryngo-videostroboscopy assessment.
      Transcranial (cortical) and mastoid (peripheral) magnetic stimulations were
      performed to evoke muscle action potentials of the thyro-arytenoid (TA) and
      cricothyroid muscles (CT). In normal volunteers, cortical stimulation leads to
      contralateral responses (cortical latency) after 10.9 and 11.3 ms and ipsilateral
      responses after 8.3 and 9.4 ms for right CT and TA muscles, respectively. There
      was a significant prolongation of cortical latency of the left TA compared with
      the right TA muscle, whilst no such significant difference was observed in the CT
      muscles. Peripheral stimulation evoked response (peripheral latency) after 2.8
      and 2.7 ms in the right CT and TA, respectively, with the same significant
      prolongation of the left TA response compared with the right side. Amongst the
      patient groups, variable patterns of laryngeal muscle response latencies
      occurred, including normal response latency, lack of response of CT and TA
      muscles, prolonged peripheral latency with secondary prolonged cortical latency
      and prolonged cortical latency with normal peripheral latency. The results
      indicate that the magnetically evoked potential of laryngeal muscles offers an
      easy, non-invasive technique and could have a role in the assessment of the
      integrity of corticolaryngeal pathways.

PMID- 11985635
TI  - Post-stroke depression, executive dysfunction and functional outcome.
AB  - The early diagnosis of vascular cognitive impairment has been challenged and
      executive control function has been suggested to be a rational basis for the
      diagnosis of vascular dementia. We sought to examine the correlates of executive
      dysfunction in a well-defined stroke cohort. A group of 256 patients from a
      consecutive cohort of 486 patients with ischaemic stroke, aged 55-85 years, was
      subjected to a comprehensive neuropsychological examination 3-4 months after
      ischaemic stroke and 188 of them in addition to detailed psychiatric examination.
      Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke
      were assessed. The DSM-III-R criteria were used for the diagnosis of the
      depressive disorders. Altogether 40.6% (n=104) of the patients had executive
      dysfunction. The patients with executive dysfunction were older, had lower level
      of education, were more often dependent, did worse in bADLs and cADLs, had more
      often DSM-III dementia, had worse cognition as measured by Mini Mental State
      Examination (MMSE) and were more depressed as measured by the BECK depression
      scale, but not with the more detailed psychiatric evaluation. They had more often
      stroke in the anterior circulation and less often in the posterior circulation.
      The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI
      1.03-1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42
      1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18-0.84).
      Clinically significant executive dysfunction is frequent after ischaemic stroke
      and is closely connected with cADLs and to overall cognitive status but could be
      distinguished from depression by detailed neuropsychological examination.
      Executive measures may detect patients at risk of dementia and disability post
      stroke.

PMID- 11985636
TI  - Functional MRI of the visual cortex and visual testing in patients with previous
      optic neuritis.
AB  - The volume of cortical activation as detected by functional magnetic resonance
      imaging (fMRI) in the visual cortex has previously been shown to be reduced
      following optic neuritis (ON). In order to understand the cause of this change,
      we studied the cortical activation, both the size of the activated area and the
      signal change following ON, and compared the results with results of
      neuroophthalmological testing. We studied nine patients with previous acute ON
      and 10 healthy persons served as controls using fMRI with visual stimulation. In
      addition to a reduced activated volume, patients showed a reduced blood
      oxygenation level dependent (BOLD) signal increase and a greater asymmetry in the
      visual cortex, compared with controls. The volume of visual cortical activation
      was significantly correlated to the result of the contrast sensitivity test. The
      BOLD signal increase correlated significantly to both the results of the contrast
      sensitivity test and to the Snellen visual acuity. Our results indicate that fMRI
      is a useful method for the study of ON, even in cases where the visual acuity is
      severely impaired. The reduction in activated volume could be explained as a
      reduced neuronal input; however, the greater asymmetry might point to a cortical
      reorganization as a consequence of neuronal damage. Future fMRI studies in ON
      will add to the understanding of the neural adaptive behaviour following ON.

PMID- 11985637
TI  - Decrease in heart ventricular ejection fraction during multiple sclerosis.
AB  - Recent studies have shown that mitoxantrone is effective in patients with active
      multiple sclerosis (MS) and that cardiac monitoring is usually required. However,
      right and left ventricular ejection fractions (VEFs) have never been studied in
      MS patients as compared with control subjects. Radionuclide angiocardiography
      (RA) was performed to assess right and left VEFs at rest in 40 consecutive
      patients with active definite MS [15 men and 25 women; mean age 33.9 +/- 10
      years; mean disease duration 8 +/- 6.5 years; 18 had relapsing-remitting and 22
      had secondary progressive forms of the disease; mean Expanded Disability Status
      Scale (EDSS) score 4.8 +/- 1.9]. The control group consisted of 40 subjects free
      of neurological or cardiovascular disease (17 men and 23 women; 44.6 +/- 13.4
      years of age). The VEF values obtained in the control group defined the normal
      limits (right VEF 32-54%; left VEF 50-74%). A statistically significant decrease
      of right (P=0.02) and left (P < 0.0001) VEFs was found in MS patients as compared
      with control subjects. RA showed pathological results for right (7.5%), left
      (10%) and both (7.5%) VEFs in 25% of MS patients. No correlation was found
      between VEF and sex, age, disease duration, disease course, EDSS score or
      previous treatment. Autonomic impairment, which frequently occurs in MS patients,
      may have accounted for the decrease in VEFs. Further physiological studies are
      required to determine factor responsible for the decrease of VEFs in MS.

PMID- 11985638
TI  - The Mures-Uzhgorod-Debrecen study: a comparison of hospital stroke services in
      Central-Eastern Europe.
AB  - Stroke mortality is extremely high in Central-Eastern European countries. The
      high rate of risk factors and differences in health care services might be among
      the factors resulting in high stroke morbidity and mortality in this region. As
      only few prospectively collected information are available from this region, we
      decided to evaluate some characteristics of stroke services in neurological
      departments of a Romanian, a Ukrainian and a Hungarian city in the framework of
      the Mures-Uzhgorod-Debrecen comparative epidemiological study. We registered
      demographic data, the absence or presence of the most important risk factors, and
      clinical signs on admission and at discharge. We recorded the application of
      various diagnostic methods, stroke treatment and recommendations for secondary
      prevention. Follow-up is planned after 30 days and after 1 year. The paper
      summarizes the methodology of this prospective epidemiological study of stroke
      patients hospitalized in neurological departments in Targu Mures, Uzhgorod and
      Debrecen, three Central-Eastern European cities in Romania, Ukraine and Hungary,
      respectively.

PMID- 11985639
TI  - Blood glucose increases early after stroke onset: a study on serial measurements
      of blood glucose in acute stroke.
AB  - The aim of this study was to evaluate if blood glucose levels change within the
      first 12 h after stroke onset and to investigate if the degree of change is
      related to stroke severity, type of stroke, or prognosis. This was a
      retrospective, descriptive trial based on 445 stroke patients with two blood
      glucose tests within 12 h of stroke onset and no history of diabetes mellitus.
      Blood glucose increased in the first 12 h after stroke onset; in mild to moderate
      stroke from 5.8 to 6.1 mmol/l (P < 0.001) and in severe stroke from 6.2 to 6.7
      mmol/l (P < 0.001). In patients who died within 7 days of stroke onset, blood
      glucose increased from 6.8 to 7.1 mmol/l (P < 0.001). In conclusion, blood
      glucose increases after the onset of acute stroke and the increase is related to
      the severity of the stroke.

PMID- 11985640
TI  - Association between seropositivity to Chlamydia pneumoniae and acute ischaemic
      stroke.
AB  - Recent studies suggest an association between Chlamydia pneumoniae infection with
      atherosclerosis, including cerebrovascular disease. We investigated the
      prevalence of Chlamydial seropositivity in patients with acute ischaemic stroke
      syndrome compared with age- and sex-matched control subjects. Specific antibodies
      (IgA) to C. pneumoniae were measured by microimmunofluorescence in both the
      clinical group (n=91) and the control group (n=112). Forty patients (43.9%) and
      34 controls (30.3%) had positive IgA titres (P < 0.05). The pooled data from this
      and previous series yielded 45% of seropositivity in cerebrovascular patients vs.
      19% in control subjects (P < 0.001). In conclusion, we suggest an association
      between chronic infection by C. pneumoniae and acute ischaemic stroke.

PMID- 11985641
TI  - Atherogenic progression of carotid stenosis associates selectively with monocyte
      fraction in circulating leukocytes.
AB  - Humoral biomarkers of inflammation appear to correlate with future cardiovascular
      events warranting investigation of more specific associations between phenotypic
      subclasses of circulating cellular immunity and atherogenic progression of
      carotid stenosis. Retrospective study of carotid stenosis progression based on
      archived serial carotid duplex ultrasonography examinations in 100 patients.
      Predictors of atherogenic progression of carotid stenosis were sought using
      univariate and multivariate analysis of age, gender, hypertension, diabetes
      mellitus, smoking, peripheral blood leukocyte count and leukocyte differential
      profile, platelets, diastolic and systolic and mean arterial blood pressure,
      pulse pressure, creatinine, glucose, total-, HDL-, and LDL-cholesterol,
      triglycerides, and body mass index. Atherogenic progression of carotid stenosis
      was limited to patients with carotid stenosis at baseline (41/100) and exhibited
      a sporadic episodic temporal course. Univariate predictors of stenosis
      progression were diabetes mellitus, smoking, percent monocytes, and absolute
      monocyte count. Logistic regression demonstrated that monocytes as a percentage
      of circulating leukocytes [odds ratio (OR) 1.25, 95% confidence interval (CI)
      1.06-1.47, P=0.0093] and smoking (OR 7.09, 95% CI 1.97-25.43, P=0.0027) were
      independently associated with atherogenic epochs. A selective association between
      the fraction of monocytes among leukocytes in peripheral blood and atherogenic
      progression of carotid stenosis is described.

PMID- 11985643
TI  - Reversible ageusia induced by losartan: a case report.

PMID- 11985642
TI  - Akinetic mutism caused by bilateral infiltration of the fornix in a patient with
      astrocytoma.
AB  - In a 59-year-old female patient, a World Health Organization (WHO) grade II
      astrocytoma had been diagnosed 16 years ago, which finally progressed into WHO
      grade III. Several right frontal neurosurgical resections, local radiation and a
      local radioimplant had been applied. Despite this long record, she was reported
      alert with a Karnofsky index of 90% until admission. Within a few weeks she
      rapidly developed akinetic mutism. Upon admission, computed tomography (CT) scan
      showed a large cystic right frontal defect and a suggested small tumor
      recurrence. White matter of the frontal lobe appeared to be translucent and
      compatible with previous radiation. The severe mental changes were initially
      attributed to a delayed radiation encephalopathy. Neuropathologically, the white
      matter of the frontal lobe showed mild elevated cell density consistent with
      gliosis; however, a tumor recurrence invading the tip of the corpus callosum and
      invading the entire length both fornices appeared. From the neuropathological
      findings of massive local tumor recurrence in both fornices, together with the
      acute clinical onset, it seems unlikely that the sequel of radiotherapy caused
      akinetic mutism, but the symmetric and severe involvement of the limbic system.
      We conclude that the rapid progression from a state of alertness to a full
      clinical picture of akinetic mutism was because of infiltration of both fornices.

PMID- 11985644
TI  - Smoking and Parkinson's disease.

PMID- 11985645
TI  - Covert vision sign.

PMID- 11985646
TI  - A stroke patient with a non-convulsive status epilepticus during citalopram
      therapy.

PMID- 11985647
TI  - Maurice Ravel and right hemisphere creativity.

PMID- 11985648
TI  - Maurice Ravel and right hemisphere creativity.

PMID- 11985657
TI  - T-cell antigen receptor signal transduction.

PMID- 11985659
TI  - Diacylglycerol kinase alpha activity promotes survival of CD4+ 8+ double positive
      cells during thymocyte development.
AB  - The diacylglycerol kinases (DGK) form a family of isoenzymes that catalyse the
      conversion of diacylglycerol (DAG) to phosphatidic acid (PA), both powerful
      second messengers in the cell. DGKalpha is expressed in brain, peripheral T cells
      and thymocytes and has been shown to translocate to the nuclear matrix upon T
      cell receptor (TCR) engagement. Here, we show that high level expression of
      DGKalpha is induced following a signal transmitted through the pre-TCR and the
      protein tyrosine kinase, lck. Activity of DGKalpha contributes to survival in
      CD4+ 8+ (DP) thymocytes as pharmacological inhibition of DGK activity results in
      death of this cell population both in cell suspension and thymic explants.
      DGKalpha promotes survival in these thymocytes through a Bcl-regulated pathway. A
      consequence of inhibition of DGKalpha is the specific down-regulation of Bcl-xl,
      whereas in transgenic mice that over-express Bcl-2, death induced by the
      inhibitor is partially blocked. Thus we report a novel activity of DGKalpha in
      survival of thymocytes immediately after entry into the DP stage in development.

PMID- 11985660
TI  - The regulation of DNAse activities in subcellular compartments of activated
      thymocytes.
AB  - Thymocytes expressing self-reactive T-cell receptors (TCR) are eliminated in the
      thymus through a TCR-mediated signal. This cell death signal (negative selection)
      generates nuclear morphological change and DNA fragmentation in thymocytes.
      However, the pathway leading to DNA fragmentation of thymocytes following TCR
      engagement remains obscure. In this study, we investigated the localization and
      function of caspase-activated DNAse (CAD) and its inhibitor (ICAD) in thymocytes
      prior to or after in vivo TCR stimulation. We showed that CAD and ICAD are co
      localized in microsome, nuclei and cytosol in unstimulated thymocytes. Following
      in vivo TCR engagement, ICAD located in cytosol and microsome was degraded and
      the resulting activated CAD induced chromosomal DNA fragmentation. CAD present in
      cytosol and microsome of unstimulated thymocytes was activated by recombinant
      caspase-3, and microsomal CAD was released to the cytosol. These results
      demonstrate that TCR engagement of thymocytes induces caspase-3-dependent
      activation of CAD localized in both cytosol and microsome, leading to DNA
      fragmentation in harmony.

PMID- 11985661
TI  - Developmentally regulated interactions of human thymocytes with different laminin
      isoforms.
AB  - The gene family of heterotrimeric laminin molecules consists of at least 15
      naturally occurring isoforms which are formed by five different alpha, three beta
      and three gamma subunits. The expression pattern of the individual laminin chains
      in the human thymus was comprehensively analysed in the present study. Whereas
      laminin isoforms containing the laminin alpha1 chain (e.g. LN-1) were not present
      in the human thymus, laminin isoforms containing the alpha2 chain (LN-2/4) or the
      alpha5 chain (LN-10/11) were expressed in the subcapsular epithelium and in
      thymic blood vessels. Expression of the laminin alpha4 chain seemed to be
      restricted to endothelial cells of the thymus, whereas the LN-5 isoform
      containing the alpha3 chain could be detected on medullary thymic epithelial
      cells and weakly in the subcapsular epithelium. As revealed by cell attachment
      assays, early CD4- CD8- thymocytes which are localized in the thymus beneath the
      subcapsular epithelium adhered strongly to LN-10/11, but not to LN-1, LN-2/4 or
      LN-5. Adhesion of these thymocytes to LN-10/11 was mediated by the integrin
      alpha6beta1. During further development, the cortically localized CD4+ CD8+
      thymocytes have lost the capacity to adhere to laminin-10/11. Neither do these
      cells adhere to any other laminin isoform tested. However, the more
      differentiated single positive CD8+ thymocytes which were mainly found in the
      medulla were able to bind to LN-5 which is expressed by medullary epithelial
      cells. Interactions of CD8+ thymocytes with LN-5 were integrin alpha6beta4
      dependent. These results show that interactions of developing human thymocytes
      with different laminin isoforms are spatially and developmentally regulated.

PMID- 11985658
TI  - Tissue-specific expression of mast cell granule serine proteinases and their role
      in inflammation in the lung and gut.
AB  - Serine proteinases with trypsin-like (tryptase) and chymotrypsin-like (chymase)
      properties are major constituents of mast cell granules. Several tetrameric
      tryptases with differing specificities have been characterized in humans, but
      only a single chymase. In other species there are larger families of chymases
      with distinct and narrow proteolytic specificities. Expression of chymases and
      tryptases varies between tissues. Human pulmonary and gastrointestinal mast cells
      express chymase at lower levels than tryptase, whereas rodent and ruminant
      gastrointestinal mast cells express uniquely mucosa-specific chymases. Local and
      systemic release of chymases and tryptases can be quantified by immunoassay,
      providing highly specific markers of mast cell activation. The expression and
      constitutive extracellular secretion of the mucosa-specific chymase, mouse mast
      cell proteinase-1 (mMCP-1), is regulated by transforming growth factor-beta1 (TGF
      beta1) in vitro, but it is not clear how the differential expression of chymases
      and tryptases is regulated in other species. Few native inhibitors have been
      identified for tryptases but the tetramers dissociate into inactive subunits in
      the absence of heparin. Chymases are variably inhibited by plasma proteinase
      inhibitors and by secretory leucocyte protease inhibitor (SLPI) that is expressed
      in the airways. Tryptases and chymases promote vascular permeability via indirect
      and possibly direct mechanisms. They contribute to tissue remodelling through
      selective proteolysis of matrix proteins and through activation of proteinase
      activated receptors and of matrix metalloproteinases. Chymase may modulate
      vascular tissues through its ability to process angiotensin-I to angiotensin-II.
      Mucosa-specific chymases promote epithelial permeability and are involved in the
      immune expulsion of intestinal nematodes. Importantly, granule proteinases
      released extracellularly contribute to the recruitment of inflammatory cells and
      may thus be involved in innate responses to infection.

PMID- 11985662
TI  - Human monoclonal natural autoantibodies against the T-cell receptor inhibit
      interleukin-2 production in murine T cells.
AB  - Natural autoantibodies (NAAbs) specific for the T-cell receptor (TCR) are present
      in all human sera, but individuals with rheumatoid arthritis (RA) generally
      produce higher titres of immunoglobulin M (IgM) isotype autoantibodies (AAbs)
      against Vbeta TCR epitopes. To investigate possible correlations between the
      specificity of such AAbs and their role in immunomodulation, we generated seven B
      cell hetero-hybridomas, secreting monoclonal IgM NAAbs, from the synovial tissue
      and peripheral blood of patients with RA. Here we report three anti-TCR
      monoclonal autoantibodies (mAAbs)--OR2, OR5 and Syn 2H-11--with the ability to
      bind subsets of murine T cells, including the ovalbumin-specific DO-11.10 clone.
      These antibodies did not induce apoptosis in vitro, but prevented interleukin-2
      (IL-2) production by antigen-specific T cells. These findings suggest an
      immunomodulatory function for NAAbs to TCR V-region epitopes and serve as the
      foundation for testing human anti-TCR mAAbs in animal models with the eventual
      goal of using them as therapeutic agents in human disease.

PMID- 11985663
TI  - Endothelial cell and cAMP regulation of T-cell CD40 ligand: relevance of
      calcium/calmodulin-dependent kinase IV signalling.
AB  - CD40 ligand (CD40L) expression is now recognized to contribute in the
      pathogenesis of vascular disease. Because increased CD40L has been associated
      with myocardial infarction, effects of endothelial cells and cAMP with respect to
      CD40L regulation may be of clinical relevance. In the present study, endothelial
      cells are shown to markedly increase CD40L on naive CD4+ T cells with a more
      modest effect on memory T cells. Furthermore, the addition of dibutyryl cyclic
      AMP (dbcAMP) synergistically increased naive cell CD40L but inhibited memory cell
      CD40L. Although it has previously been recognized that human endothelial cells
      can increase T-cell CD40L, this is the first description of the difference in
      responses of naive and memory cells and the first demonstration of synergistic
      effects of endothelial cells and cAMP on CD40L regulation. Consistent with
      previous reports that CD40L regulation is distinctive, another marker of early
      activation (CD69) was not similarly regulated. The mechanisms of CD40L regulation
      were related to calcineurin and calcium/calmodulin dependent kinase IV (CaMKIV)
      signalling pathways. Endothelial cell costimulation of CD40L was found to be
      dependent upon calcineurin activity while cAMP actions to increase CD40L were
      dependent upon CaMKIV. Expression of a dominant negative CaMKIV construct further
      indicated an important role for CaMKIV in regulation of CD40L and cAMP responses.
      These data indicate that endothelial cell costimulation can interact with cAMP
      through calcium signalling pathways to synergistically enhance CD40L expression.
      Because increased CD40L is associated with atherosclerotic plaque and
      instability, results are relevant to the pathogenesis of atherosclerosis and
      myocardial infarction.

PMID- 11985664
TI  - Identification and characterization of L-selectin ligands in porcine lymphoid
      tissues.
AB  - A human L-selectin-ZZ fusion protein was used to screen porcine inguinal lymph
      nodes for the presence of monoclonal antibody (mAb) MECA 79-negative ligands.
      Fractionation of lymph node-conditioned medium by anion-exchange chromatography
      revealed two distinct L-selectin-binding fractions, one containing a MECA 79 non
      reactive species and the second containing two MECA 79 reactive species of
      approximately 84 000 and 210 000 molecular weight. The MECA 79 non-reactive
      species exhibited Ca2+- and lectin-dependent binding to L-selectin-ZZ in a solid
      phase capture enzyme-linked immunosorbent assay (ELISA), and this was
      specifically disrupted by the addition of EDTA, mannose-6-phosphate and the
      blocking anti-L-selectin mAb, DREG-56. Enzymatic characterization of the ligand
      by trypsin, O-sialoglycoprotease endopeptidase, heparinases I and III, or
      chondroitinase ABC lyase digestion indicated that L-selectin binding was
      predominantly dependent upon a chondroitin sulphate-modified glycoprotein
      determinant. Although Coomassie Blue staining of sodium dodecyl sulphate (SDS)
      polyacrylamide gels did not reveal a detectable protein species, carbohydrate
      specific staining using GlycoTrack revealed a single, heavily glycosylated
      protein of high molecular weight (> 220 000). These studies have revealed the
      existence of a MECA 79 non-reactive, chondroitin sulphate glycosaminoglycan
      modified ligand, termed csgp>220, which is secreted by peripheral lymph nodes and
      may play a role in leucocyte trafficking to the lymph node.

PMID- 11985665
TI  - Crucial Fas-Fas ligand interaction in spontaneous acceptance of hepatic
      allografts in mice.
AB  - The Fas/Fas ligand (FasL) system plays important roles in the immune system,
      including host immunoregulation and cytotoxicity. In this study, we investigated
      the involvement of Fas-FasL interactions in spontaneous acceptance of hepatic
      allografts in murine orthotopic liver transplantation. Liver transplantation
      between the C57BL/6 (B6, H-2b) donor and the MRL/Mp (MRL, H-2k) recipient was
      performed in various combinations of donor and recipient mice with wild type
      (+/+), Fas-mutant (lpr) or FasL-mutant (gld) genotypes. The prolongation and
      spontaneous acceptance of the fully allogeneic grafts in recipients was not
      observed in either MRL-lpr recipients with B6+/+ livers or MRL+/+ recipients with
      B6-gld livers. Moreover, the serum alanine aminotransferase (ALT) levels and the
      degree of cell infiltration into hepatic allografts on day 7 after
      transplantation were inversely correlated with the recipient survival time (in
      days). The donor-specific cytotoxic T-lymphocyte (CTL) activities of the graft
      infiltrating cells (GICs) from MRL-gld recipients with B6+/+ livers were much
      lower than those from MRL+/+ or -lpr recipients on days 5 and 10 after
      transplantation. However, the CTL activities of the GICs from MRL+/+ and -gld
      recipients predominantly disappeared by day 15 after transplantation.
      Furthermore, the anti-donor CTL activities induced in MRL+/+ recipients were
      ascribed to CD8+ cells, and were not mediated by Fas-FasL interactions. These
      results strongly suggest that the Fas/FasL system plays a critical role for
      recipient immunoregulation, enabling recipients in accepting hepatic allografts
      by deletion of the donor-specific T cells, but not for CTL/target cell
      interaction in MRL+/+ recipients.

PMID- 11985666
TI  - Age-related telomere length dynamics in peripheral blood mononuclear cells of
      healthy cynomolgus monkeys measured by Flow FISH.
AB  - Telomere length is a good biomarker to study the cellular senescence as well as
      aging of an organism, because it regulates the replicative capacity of vertebrate
      somatic cells. To demonstrate age-related telomere length dynamics in the
      peripheral blood mononuclear cells (PBMC) of the cynomolgus monkey, we introduced
      a novel method of measuring telomere length by fluorescence in situ hybridization
      with a Peptide Nucleic Acid (PNA) labelled probe and flow cytometry (Flow FISH).
      A highly significant correlation was observed between the intensity of telomere
      specific fluorescence by Flow FISH and telomere length by Southern blot analysis
      (R = 0.923, n = 22). The intensity of telomere fluorescence in PBMC significantly
      decreased with age in 55 monkeys aged from 0 to 34 years and this decrease
      corresponded to the loss of 62.7 base pairs per year (R = - 0.52, P < 0.00004).
      We also analysed the expression of naive cell-associated markers, CD28, CD62L and
      CD45RA/CD62L in T lymphocytes of 47 cynomolgus monkeys. An age-related increase
      in the CD28- subset was observed in CD8+ T lymphocytes in monkeys less than 11
      years old and in CD4+ T lymphocytes in monkeys over 23 years old, respectively.
      The percentage of CD62L+ subsets was significantly decreased with age in both
      CD4+ (R = - 0.55) and CD8+ T lymphocytes (R = - 0.73). From the comparison of
      telomere length among PBMC, CD62L+ and CD62L- T lymphocytes, it was clearly
      evident that loss of naive subsets results in the shortening of telomere length
      in vivo. These results show that this method can be applicable to studying the
      turnover and precursor-progeny of PBMC in cynomolgus monkeys as an animal model
      of aging.

PMID- 11985667
TI  - Influence of ageing on Langerhans cell migration in mice: identification of a
      putative deficiency of epidermal interleukin-1beta.
AB  - Previous studies in mice have reported a decrease in epidermal Langerhans cell
      (LC) density in aged skin, however, the impact of this reduction on LC function
      and cutaneous immune responses is unclear. In the present series of experiments,
      the frequency of major histocompatibility complex class II+ LC in the epidermis
      of older (6-month-old) mice was found to be reduced significantly compared with
      that observed for young (6-8-week-old) mice. LC mobilization and the subsequent
      accumulation of dendritic cells (DC) in regional lymph nodes in response to
      topical challenge with a chemical allergen were found to be less vigorous in
      older mice. Flow cytometric analyses of DC derived from the draining lymph nodes
      of fluorescein isothiocyanate (FITC)-sensitized mice revealed that the frequency
      of FITC+-DC arriving in draining lymph nodes was also reduced in older mice but
      that the fluorescence intensity was comparable. Control and allergen-treated
      older mice also displayed decreased total lymph node cellularity. Contact
      hypersensitivity responses were found not to be compromised in older mice.
      However, the cytokine regulation of LC migration in the two age groups of mice
      did differ. LC migration provoked by intradermal injection of tumour necrosis
      factor-alpha (TNF-alpha) was reduced in older animals, whereas, the percentage of
      LC that migrated in response to exogenous interleukin-1beta (IL-1beta) was
      comparable for both young and aged mice. Since both allergen- and TNF-alpha
      induced LC responses are known to require receipt by LC of a signal from IL-1beta
      for effective migration, the suggestion is that impaired LC migration in older
      mice may be due to a reduced availability of epidermal IL-1beta.

PMID- 11985668
TI  - HeLa cells cocultured with peripheral blood lymphocytes acquire an immuno
      inhibitory phenotype through up-regulation of indoleamine 2,3-dioxygenase
      activity.
AB  - The mechanisms by which tumour cells escape recognition by the immune system or
      subvert antitumour effector responses remain poorly understood. In the course of
      investigating the potential of costimulatory signals in anticancer immunotherapy
      strategies, we have observed that HeLa cells (a human cervical carcinoma cell
      line) cocultured with peripheral blood lymphocytes (PBL) acquire the capacity to
      inhibit PBL proliferation in response to interleukin-2 (IL-2). This immuno
      inhibitory phenotype was further shown to result from induction of the tryptophan
      catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO), by interferon-gamma (IFN
      gamma) secreted from cocultured allo-reactive PBL. This enzyme has recently been
      shown to be a critically important modulator of immunological responses, most
      notably through the capacity to protect allogeneic concepti from alloreactive
      maternal lymphocytes. While the cytostatic consequences of IDO activity in tumour
      cells has received attention, the data presented in this report support the
      hypothesis that IDO activity may also act to impair antitumour immune responses.

PMID- 11985669
TI  - Lung dendritic cells are primed by inhaled particulate antigens, and retain MHC
      class II/antigenic peptide complexes in hilar lymph nodes for a prolonged period
      of time.
AB  - Intratracheal (IT) administration of heat-killed Listeria monocytogenes (HKL)
      results in an influx of macrophage and dendritic cell (DC) precursors into the
      lung interstitium. Low-density, FcR+, interstitial lung cells isolated from rats
      instilled 24 hr before with HKL or vehicle alone, were > 90% Mar1+. After
      culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3
      days, up to 24% of the loosely adherent cells were DC that stimulated allogeneic
      T-cell proliferation in an mixed lymphocyte reaction (MLR) assay. After only an
      overnight incubation with GM-CSF, however, the capacity of interstitial Mar1+
      cells to stimulate HKL immune T-cell proliferation without exogenous antigen was
      low. By contrast, when DC were isolated as major histocompatibility complex (MHC)
      class II+ cells from rat lungs at 1, 3, 7 and 14 days after HKL instillation and
      cultured overnight with GM-CSF, their antigen presentation capacity without added
      exogenous antigen was robust, but declined over the 2-week period. Interestingly,
      hilar lymph node DC maintained their HKL antigen-presenting capacity for up to 2
      weeks after instillation of HKL. Following IT administration of PKH-26 labelled
      HKL, fluorescent or immunolabelled organisms were detected in OX62+ DC in airway
      epithelium, lung interstitium and hilar lymph nodes in situ and in MHC class II+
      DC isolated from these sites. We conclude that newly immigrated Mar1+ lung DC
      precursors, while efficient in endocytosing particulate antigens, are incapable
      of eliciting a significant proliferative response from HKL-sensitized T cells. By
      contrast, MHC class II+ DC isolated from lungs and incubated overnight with GM
      CSF induce vigorous antigen-specific T-cell proliferation. Antigen-loaded lung DC
      in hilar lymph nodes maintain their antigen presentation capacity for up to 2
      weeks.

PMID- 11985670
TI  - Local T-cell activation after segmental allergen challenge in the lungs of
      allergic dogs.
AB  - Dogs with immunoglobulin E (IgE) allergy for ragweed that are sensitized by
      intrapulmonary exposure to ragweed can be used to study the pulmonary immune
      response that is important in allergic asthma. Using this model, we tested the
      hypothesis that T lymphocytes are activated locally in the airways shortly after
      allergen exposure of the lungs. The airways of six allergic dogs and three non
      allergic dogs were exposed to ragweed by segmental allergen challenge (SAC). T
      cell subsets and T-cell activation in blood and bronchoalveolar lavage (BAL)
      fluid were measured by flow cytometry before SAC and at 4, 24 and 72 hr
      thereafter. SAC caused a statistically significant increase in the percentage of
      major histocompatibility complex (MHC) class II-positive CD4 and CD8 T cells in
      BAL fluid and a significant increase in the mean fluorescent activity of MHC
      class II from 4 hr after SAC onward. This activation was significantly different
      from that found in cells from lung lobes challenged with saline, or from lung
      lobes in non-allergic dogs challenged with ragweed. The percentage of
      CD45RA(bright) CD8 cells increased significantly in allergic dogs after both
      ragweed and saline challenges. This was significantly higher than in non-allergic
      dogs. We conclude that T-cell activation in the airways of dogs can be measured
      after in vivo activation of the cells by measuring MHC class II and CD45RA
      expression in BAL fluid T cells. Furthermore, in allergic dogs, T cells are
      activated locally in the lungs within 4 hr after exposure to ragweed allergen.
      These results suggest a role for T lymphocytes in the development of late-phase
      allergic reactions in the airways.

PMID- 11985671
TI  - Lack of Shiga-like toxin binding sites in germinal centres of mouse lymphoid
      tissues.
AB  - B cells in germinal centres are known to express carbohydrate antigen CD77 in
      human lymphoid tissues. The CD77 antigen is specifically recognized by Shiga-like
      toxins (SLTs) that are produced by enterohaemorrhagic Escherichia coli O157:H7.
      To determine whether the binding subunits of Shiga-like toxin-1 (SLT-1B) could
      have adverse effects on the murine immune system when used as an immunogen, we
      investigated whether SLT-1B could bind to germinal centres of mouse lymphoid
      tissues. Frozen sections of peripheral lymph nodes and Peyer's patches from
      immunized mice were tested for the presence of SLT-1B-binding sites by
      immunohistological methods. Germinal centres were not stained with SLT-1B, while
      they were intensely stained with peanut agglutinin (PNA), another marker of
      germinal centres. On the other hand, SLT-1B specifically bound to renal tubules
      and collecting ducts in frozen sections of mouse kidney. This is consistent with
      results from human tissues. We also demonstrated that B220/PNA double-positive
      populations in lymph nodes from immunized mice exhibited only marginal staining
      with SLT-1B. The present results suggest that SLTs would not impede germinal
      centre functions of the murine immune system.

PMID- 11985672
TI  - Administration of plasmids expressing interleukin-4 and interleukin-10 causes
      BALB/c mice to induce a T helper 2-type response despite the expected T helper 1
      type response with a low-dose infection of Leishmania major.
AB  - BALB/c mice are susceptible to developing an infection with Leishmania major as a
      result of a fatal T helper 2 (Th2)-type response. However, mice infected with a
      low dose of parasites are reported to be able to overcome the lesions associated
      with a T helper 1 (Th1)-type response. To clarify why a difference in the dose of
      parasites induces a difference in the polarization of the Th phenotype, we first
      attempted to measure cytokine production. Soon after infection, the mice given
      high doses of parasites produced elevated levels of both Th1 [interferon-gamma
      (IFN-gamma)] and Th2 [interleukin (IL)-4 and IL-10] cytokines. However, when
      assessed at 1 and 2 weeks after infection, no significant difference in the
      balance of Th1 and Th2 cytokines could be detected between mice infected with low
      or high doses of L. major. These results support the notion that the Th2 cytokine
      levels at an early phase of infection could be a key factor for the induction of
      a Th2 response. In order to assess the efficacy of Th2 cytokines, the mice
      infected with low doses of L. major were co-administered IL-4 plasmid and IL-10
      plasmid. Consequently, the mice (which originally exhibited a Th1 response)
      showed progressive disease and developed a Th2 response. However, administration
      of these plasmids at 7 days postinfection could not alter the Th polarization.
      Furthermore, production of IL-12 from the spleen cells stimulated by L. major was
      suppressed in the presence of IL-4 and IL-10. These results strongly suggest that
      the susceptibility to L. major in BALB/c mice depends on the persistence of Th2
      cytokine levels at an early phase of infection.

PMID- 11985673
TI  - Mechanisms involved in the resistance of Enterococcus faecalis to calcium
      hydroxide.
AB  - AIM: This study sought to clarify the mechanisms that enable E. faecalis to
      survive the high pH of calcium hydroxide. METHODOLOGY: E. faecalis strain JH2-2
      was exposed to sublethal concentrations of calcium hydroxide, with and without
      various pretreatments. Blocking agents were added to determine the role of stress
      induced protein synthesis and the cell wall-associated proton pump. RESULTS: E.
      faecalis was resistant to calcium hydroxide at a pH of 11.1, but not pH 11.5. Pre
      treatment with calcium hydroxide pH 10.3 induced no tolerance to further exposure
      at pH 11.5. No difference in cell survival was observed when protein synthesis
      was blocked during stress induction, however, addition of a proton pump inhibitor
      resulted in a dramatic reduction of cell viability of E. faecalis in calcium
      hydroxide. CONCLUSIONS: Survival of E. faecalis in calcium hydroxide appears to
      be unrelated to stress induced protein synthesis, but a functioning proton pump
      is critical for survival of E. faecalis at high pH.

PMID- 11985674
TI  - Radiographic evaluation of the prevalence and technical quality of root canal
      treatment in a French subpopulation.
AB  - AIM: This study was undertaken to examine the prevalence and technical quality of
      root fillings and the periapical status of endodontically treated teeth in a
      French subpopulation. METHODOLOGY: Full-mouth periapical radiographs were
      obtained from 208 consecutive adult patients seeking care within the dental
      service provided by the Hotel-Dieu in Paris. The occurrence and technical quality
      of root fillings were assessed for each root according to the position and the
      density of the obturation. The periapical status was evaluated using the
      Periapical Index Scoring System. The type of coronal restoration and the presence
      of posts were also noted. RESULTS: Of the 8743 roots included in the survey, 23%
      were root-filled. An acceptable standard of treatment was found in 21% of roots
      with 16% of these cases associated with signs of periapical disease. In roots
      with unacceptable root-fillings, 27% had periapical pathology. A post was seen in
      26% of the root-filled canals, with 29% of these cases associated with periapical
      pathology. An intracoronal restoration existed in 30% of the filled roots, of
      which 22% exhibited a periapical lesion. An extra-coronal restoration was present
      in 60% of the filled roots, of which 24% had radiographic signs of periapical
      pathology. The remaining 10% of filled roots that had no coronal restoration were
      associated with periapical pathology in 33% of cases. At least one periapical
      lesion was seen in 63% of the patients. CONCLUSION: The results demonstrate a
      high prevalence of root-filled teeth and poor technical quality of treatment.
      Roots presenting with acceptable root fillings were associated with a lower
      prevalence of periapical pathology (P < 0.001). Posts in roots were associated
      with periapical pathology significantly more than in roots without posts (P <
      0.001).

PMID- 11985675
TI  - An in vitro comparison of pH changes in root dentine following canal dressing
      with calcium hydroxide points and a conventional calcium hydroxide paste.
AB  - AIM: This study aimed to measure and compare pH changes at apical and cervical
      sites on the external root surface of extracted teeth dressed with calcium
      hydroxide in two different formulations. METHODOLOGY: Root canals of 45 single
      rooted extracted human teeth were accessed and shaped using a step-down technique
      with rotary instrumentation. Standard cavities were prepared on the external root
      surface at specific apical and cervical sites. The teeth were randomly allocated
      to three groups. Teeth in group A were dressed with calcium hydroxide points,
      those in group B were dressed with an aqueous calcium hydroxide paste and teeth
      in group C were left unfilled. Following storage in humid conditions, the pH of
      the dentine at apical and cervical sites was measured at baseline and then at 24
      h, 72 h, 1 week, 10 days, 2 weeks and 3 weeks. RESULTS: The pH of the root
      dentine at both apical and cervical sites was significantly greater (P < 0.001)
      in teeth dressed with aqueous calcium hydroxide paste compared with those dressed
      with calcium hydroxide points, when averaged out across all time periods. For all
      groups, there was a significant difference between the mean apical and cervical
      pH values for each tooth with lower values for the apical sites (P < 0.001).
      CONCLUSION: The results of this study indicate that an aqueous calcium hydroxide
      paste was more effective than calcium hydroxide points at raising the pH on the
      external root surface of extracted teeth.

PMID- 11985676
TI  - The dentinogenic effect of mineral trioxide aggregate (MTA) in short-term capping
      experiments.
AB  - AIM: The objective of the present experiment was to study the early pulpal cell
      response and the onset of reparative dentine formation after capping application
      of MTA in mechanically exposed pulps. METHODOLOGY: Thirty-three teeth from three
      dogs, 12-18 months of age were mechanically exposed via class V cavities. Light
      pressure was applied to control haemorrhage. ProRoot MTA (Dentsply Simfra, Paris)
      was placed at the exposure site and light pressure was applied with a wet cotton
      pellet. The cavities were restored with amalgam and the pulpal tissue reactions
      were assessed by light and electron microscopy (transmission and scanning) after
      healing intervals of 1, 2 or 3 weeks. RESULTS: A homogenous zone of crystalline
      structures was initially found along the pulp-MTA interface, whilst pulpal cells
      showing changes in their cytological and functional state were arranged in close
      proximity to the crystals. Deposition of hard tissue of osteotypic form was found
      in all teeth in direct contact with the capping material and the associated
      crystalline structures. Formation of reparative dentine (tubular matrix formation
      in a polar predentine-like pattern by elongated polarized cells) was consistently
      related to a firm osteodentinal zone. CONCLUSIONS: The present experiments
      indicate that MTA is an effective pulp-capping material, able to stimulate
      reparative dentine formation by the stereotypic defensive mechanism of early
      pulpal wound healing.

PMID- 11985677
TI  - Guided bone regeneration (GBR) using membranes and calcium sulphate after
      apicectomy: a comparative histomorphometrical study.
AB  - AIM: The purpose of the present study was to evaluate the effects of resorbable
      and non-resorbable membranes, and calcium sulphate on bone regeneration in
      osseous defects in conjunction with apicectomy. METHODOLOGY: The mandibular third
      and fourth premolars of 12 beagle dogs were root treated, and apicectomies were
      performed. The osseous defects were divided randomly into five groups. In groups
      A, B and C the osseous defects were covered with e-PTFE membranes, PLGA
      membranes, and collagen membranes, respectively. In group D, defects were filled
      with calcium sulphate. Nothing was used in group E, which served as controls. The
      dogs were sacrificed 4, 8, and 16 weeks after the surgery. Undemineralized
      sections were obtained and evaluated histomorphometrically. RESULTS: Newly formed
      cortical bone had closed the defect in the cortical plate in all groups at 16
      weeks. The degree of concavity of the new cortical bone at 16 weeks in groups A
      and D was significantly less than in group B (P < 0.01). The percentage of
      regenerated bone in group A was significantly greater than in groups B (P <
      0.01), C (P < 0.05) and E (P < 0.05). In group D, it was significantly greater
      than in groups B (P < 0.01) and E (P < 0.05). CONCLUSIONS: The data suggests that
      e-PTFE membrane is more effective compared to resorbable membranes and controls
      for bone regeneration after apicectomy, and that calcium sulphate could be
      substituted for e-PTFE membrane.

PMID- 11985678
TI  - Does the first file to bind correspond to the diameter of the canal in the apical
      region?
AB  - AIM: The aim of this study was to determine whether the first file that binds at
      the working length corresponds to the canal diameter. METHODOLOGY: Two similar
      groups (n = 10) of mandibular premolars with curved canals were selected on the
      basis of their morphology. Following access and pulp tissue removal, the first
      instrument that bound in each canal at the working length was determined. In one
      group the instrument used was a K-file, in the other group a Lightspeed
      instrument was used. After fixing the instruments in place, the apices were
      ground to the level of the working length and the diameters of both the
      instrument and the apical canal were recorded. RESULTS: In 75% of the canals, the
      instruments bound at one side of the wall only; in the other 25%, the instrument
      did not contact the wall. In 90% of the canals, the diameter of the instrument
      was smaller than the short diameter of the canal; this discrepancy was up to 0.19
      mm. No significant difference in discrepancy was found between instruments (P >
      0.05). CONCLUSIONS: Neither the first K-file nor the first Lightspeed instrument
      that bound at the working length accurately reflected the diameter of the apical
      canal in curved mandibular premolars. It is uncertain whether dentine can be
      removed from the entire circumference of the canal wall by filing the root canal
      to three sizes larger than the file that binds first.

PMID- 11985679
TI  - An in vitro comparison of the bactericidal efficacy of lethal photosensitization
      or sodium hyphochlorite irrigation on Streptococcus intermedius biofilms in root
      canals.
AB  - AIM: To compare the bacterial killing of Streptococcus intermedius biofilms in
      root canals using lethal photosensitization with various combinations of
      photosensitizer concentration and laser light dose or 3% sodium hypochlorite
      (NaOCl) irrigation. METHODOLOGY: Extracted teeth (n = 35) with single canals were
      selected and the canals prepared to apical size 25 with a 10% taper. The teeth
      were autoclaved and the canals inoculated with Streptococcus intermedius in brain
      heart infusion broth and were incubated for 48 h to allow a biofilm to form. The
      teeth were then subjected to 3% NaOCl irrigation (n = 4) or lethal
      photosensitization using combinations of a range of toluidine blue O (TBO)
      photosensitizer concentrations (12.5, 25, 50, 100 microgram/mL-1) and light doses
      (60, 90, 120, 300, 600 s equivalent to energy doses of 2.1-21 J) using a 35-mW
      helium-neon low power laser targeted at the access cavity (n = 4 for each
      combination). Controls consisted of laser light only (TBO = 0 microgram/mL-1) (n
      = 4), TBO only (light dose = 0 s) (n = 4), and no treatment (positive control n =
      17). Following treatment the canal contents were sampled with sterile paper
      points, the sample was dispersed in transport medium, serially diluted and
      cultured on blood agar to determine the number of colony forming units (CFU).
      RESULTS: The combination of 100 microgram/mL-1 TBO and 600 s (21 J) of laser
      energy achieved maximum reduction in recovered viable bacteria (5 log10 CFU). TBO
      at low concentrations (< or =50 microgram/mL-1) was not bactericidal but
      treatment with 100 microgram/mL-1 TBO alone reduced recovered viable bacteria by
      3 log10 CFU. Laser light alone had limited bactericidal effect. No viable
      bacteria were recovered following treatment with 3% NaOCl. CONCLUSIONS: The
      combined use of a photosensitizing agent and a low power laser directed at the
      access cavity was bactericidal to S. intermedius biofilms in root canals but was
      unable to achieve total kill, unlike 3% NaOCl.

PMID- 11985680
TI  - The long-term sealing ability of an epoxy resin root canal sealer used with five
      gutta percha obturation techniques.
AB  - AIM: The aim of the present study was to evaluate the long-term sealing ability
      (both apical and coronal) of an epoxy resin root canal sealer (AH26) when used
      with different gutta-percha obturation techniques. METHODOLOGY: Straight single
      rooted teeth with mature apices were divided into 10 groups of 75 teeth and one
      group of 40 control teeth. Root canals were prepared according to the crown
      down/step-back technique and using both 2.5% sodium hypochlorite and an EDTA
      paste. Root canals were obturated using cold lateral condensation, warm vertical
      condensation and hybrid condensation of gutta-percha; and with Thermafil and Soft
      Core obturators. AH26 was used as the sealer in all cases. After root canal
      filling, each group was divided into five individual groups of 15 teeth. The
      first group of 15 teeth was kept for 1 day, the second for 1 week, the third for
      4 months, the fourth for 6 months and the fifth for 12 months at 37 degrees C in
      vacutainers in 80% relative humidity. The teeth were immersed in India ink for 90
      h, each root was split and sectioned longitudinally, and the maximum extent of
      leakage was measured using a stereomicroscope at x6 magnification. RESULTS:
      Leakage occurred whatever filling technique was combined with AH26. The number of
      teeth with gross leakage increased with time up to 4 months, but did not appear
      to increase between 6 and 12 months storage. The degree of apical leakage and the
      number of leaking teeth in the Soft-Core obturator groups was significantly
      higher than all four other gutta-percha obturation techniques. Up to 4 months the
      degree of coronal leakage and the number of leaking teeth in the Thermafil groups
      was significantly higher than the other gutta-percha obturation techniques,
      except for Soft-Core. In the Soft-Core obturator groups the degree of coronal
      leakage and the number of leaking teeth was significantly higher than the other
      gutta-percha obturation techniques, except for Thermafil at all evaluation times.
      CONCLUSION: The hybrid gutta-percha condensation technique was superior to the
      other four obturation techniques in respect of apical leakage. Coronal leakage
      was significantly greater during the first 4 months for the Thermafil system as
      compared to the three condensation techniques; coronal leakage was significantly
      greater at all time periods for the Soft-Core system. There were no significant
      differences between the Thermafil and the Soft-core system.

PMID- 11985681
TI  - A comparison of the shaping characteristics of two nickel-titanium endodontic
      hand instruments.
AB  - AIM: The purpose of this study was to compare the shaping characteristics of Ni
      Ti K-files and Ni-Ti S-files manipulated by hand. METHODOLOGY: A total of 60
      extracted human roots were embedded in resin blocks. The embedded roots were
      divided into three groups: (i) roots with straight; (ii) apically curved; and
      (iii) continuously curved canals. Each of the three groups was randomly divided
      into two subgroups; one subgroup in each group was prepared with Ni-Ti K-files
      and the other with Ni-Ti S-files. The files were used with a step-back technique
      and enlarged so that the master apical file was size 30, and the canals were
      stepped back to size 40. The performance of the files was assessed by the
      superimposition of projected radiographs taken in bucco-lingual and mesio-distal
      directions before and after the preparation. The results were analysed
      statistically using analysis of covariance and Duncan's multiple range test.
      RESULTS: Although canal preparation using Ni-Ti K-files was quicker, there were
      no statistically significant differences between file types. The Ni-Ti S-file
      removed significantly more material at the most coronal level (P < 0.05). There
      were minor differences between instruments at the apical level. Only in the
      proximal view of apically curved canals prepared with Ni-Ti S-files was
      significantly more dentine removed from the outer aspect of the curvature (P <
      0.05). At the middle level (wide danger zone) the Ni-Ti S-files removed more
      dentine from the inner aspect of the curvature in those roots with apically
      curved canals. CONCLUSIONS: Under the conditions of this study, preparation with
      Ni-Ti K-files produced more appropriate shapes in roots with apically curved
      canals than Ni-Ti S-files.

PMID- 11985684
TI  - Swiss nurses' knowledge related to health care reforms: an exploratory study.
AB  - BACKGROUND: This study examines health care reforms' implementation processes
      from the perspective of nurses' knowledge regarding the reforms. The research has
      been carried out in the Swiss (Canton Vaud) context, where health care reforms
      have been initiated, on the National (Federal) level, in 1996. OBJECTIVES: Three
      research questions were formulated: (a) What is the level of nurses' knowledge
      regarding the basic principles of LAMal (Loi federale sur l'assurance maladie,
      Federal Health Insurance Law)? (b) What is the level of nurses' knowledge
      concerning the principles of health care reforms in Canton Vaud (NOPS, Nouvelles
      Orientations de la Politique Sanitaire)? and (c) Are there knowledge differences
      relating to employment setting (hospital, community, and education), nurses'
      roles (managerial vs. staff nurses) and level of education? METHODS: The sample
      consisted of a total of 74 nurses. Of these, 20 were employed in the community,
      30 in hospital settings and 24 worked in schools of nursing. The research tool
      utilized was 40-items nurses' knowledge questionnaire developed for the purpose
      of this study. Three knowledge subscales and a subscale of certainty were
      constructed. RESULTS: Overall, data showed a moderate to high mean level of
      knowledge (around 70% correct responses) on all knowledge scales considered.
      Community setting, managerial position, and a nonacademic nursing degree were all
      positively related to higher levels of reforms' knowledge. On the contrary,
      employment in a hospital setting and having a university degree had both negative
      impacts on achieving a high score of knowledge. Levels of certainty were
      significantly higher for LAMal than NOPS and for correct rather than for wrong
      responses.

PMID- 11985685
TI  - The role of ritualistic ceremonial in removing barriers between subcultures in
      the National Health Service.
AB  - The role of ritualistic ceremonial in removing barriers between subcultures in
      the National Health Service Background. One of the ways in which it is possible
      to achieve successful organizational change is through the elimination of those
      ceremonies that reinforce or preserve the negative aspects of professional and
      work group autonomy, thus maintaining the barriers between subcultures.
      Conversely, the encouraging of ceremonies which reinforce positive aspects is
      likely to achieve more flexible, team-orientated changes. Aim. The paper
      considers those ceremonies, which perpetuate barriers in a National Health
      Service (NHS) Trust, and explores new ceremonies which may question, weaken or
      eliminate current dysfunctional practices. Design. Our research approach was
      mainly phenomenological, as we wished to elicit the symbolic significance of
      organizational routines. The primary source of data was spoken language. The
      findings are based on purposive sampling of informants by means of semi
      structured interview and observation. Other types of information were also
      collected, including business plans, reports and brochures. Informants included
      the Chief Executive and four Board members, three consultants, the director of
      nursing and midwifery, 10 middle managers and eight junior, nonmedical and
      nonmanagerial employees. Findings. Two broad bands of ceremonies have been
      identified - those which preserve the existing norms and autonomy of professional
      and worker groups, which we have named Ceremonies of Preservation, and those
      which encourage change, which we have called Ceremonies of Change. Considerable
      data are provided to help to 'tell the story'. Conclusion. The paper argues that
      attention to ceremonial in the wider change process may facilitate the desired,
      specific change or changes in practice. It suggests that changes which confront
      unnecessary demarcation, but which do not undermine professional integrity, can
      create real benefits for NHS hospitals.

PMID- 11985686
TI  - A discipline-specific determination of high quality nursing care.
AB  - AIM: The purpose of this study is to establish a framework for defining quality
      of care based in nursing's unique body of knowledge through identification of
      nursing actions associated with high quality care. RATIONALE: Nurses are legally
      liable and morally responsible for the quality of the care they provide to
      patients. Yet the meaning of 'high quality nursing care' remains ambiguous mainly
      because models used to define it are borrowed from other disciplines. DESIGN: Two
      frameworks, quality and nursing knowledge, guided the selection and review of
      this literature review. The third framework of learning domains, an educational
      theory, assisted in organizing the data gathered from the literature. FINDINGS:
      Attributes of high quality nursing care as perceived by both patients and nurses
      are described. Despite a professed philosophy of holism and humanism, nursing
      relies heavily on the industrially derived structure-process-outcome model with
      current emphasis on outcomes. CONCLUSIONS: Patient outcomes are the product of
      the service nurses deliver and are appropriate as defining criteria only when
      care is being evaluated from the patient's perspective. Defining quality from the
      nursing profession's frame of reference focuses on evaluating the services
      provided; that is, nursing actions and behaviours, linked to the use of nursing
      knowledge. High quality nursing equates with competence in the cognitive,
      affective, and psychomotor domains.

PMID- 11985687
TI  - Deciphering the 4 D's: cognitive decline, delirium, depression and dementia--a
      review.
AB  - PURPOSE: The purpose of this paper is to assist advanced practice nurses to
      recognize, identify, and diagnose cognitive change in older adults.
      BACKGROUND/RATIONALE: Optimal cognitive function is important for continued
      independence, and yet changes in cognition are frequently unrecognized among
      older adults. Cognitive change in older adults can be observed due to age-related
      cognitive decline, the development of acute confusion (delirium), depression,
      dementia and/or a combination of these. When the aetiological source for
      alterations in cognitive function is delirium or depression, the potential for
      reversibility mandates that the reason for the cognitive change be identified
      with steps taken to remedy the situation. Also, early recognition of dementia is
      an important factor in obtaining timely and appropriate care. These conditions
      can exist concurrently and may fluctuate making deciphering the reason for the
      cognitive change problematic. CONCLUSIONS: It is essential to understand how the
      4 'D's' are expressed and to recognize the potential contributing factors to an
      observable change in cognitive function for diagnosis and treatment.
      Recommendations for obtaining a person's history are included.

PMID- 11985688
TI  - Supporting and policing mothers: an analysis of the disciplinary practices of
      health visiting.
AB  - AIM: This paper draws on the notion of disciplinary power developed by Michel
      Foucault to discuss whether the professional practices inherent in British health
      visiting can be understood in terms of support or surveillance. BACKGROUND: The
      notion of disciplinary power embedded within Foucault's writings has been widely
      applied to the sociological analysis of health care professions. While a number
      of studies have focused on nursing practice, there has been little empirical work
      developing these ideas in the context of British health visiting. METHODS: A
      qualitative approach using interviews with 24 health visitors and 16 women who
      had experienced domestic violence was used. For reasons of confidentiality, the
      women were not matched to the health visitors. Data analysis was continuous with
      data collection and led to identification of a number of categories. The
      theoretical framework of feminist poststructuralism underpinned the analysis.
      FINDINGS: The women who participated in this research described their engagement
      in a number of disciplinary practices. These included the discursive production
      of themselves as good mothers, subjects and objects of the health visiting gaze,
      as well as their practices of resistance to health visiting work. Analysis of the
      health visitors' interview data provided further evidence concerning the exercise
      of disciplinary power in their everyday work of providing support and health care
      to women and children. CONCLUSIONS: The paper highlights tensions within the
      health visitor's role between welfare and surveillance, as well as differences
      between lay and professional perspectives.

PMID- 11985689
TI  - Defining and measuring nursing productivity: a concept analysis and pilot study.
AB  - AIMS: The purpose of this article is fourfold. First we report a concept analysis
      of nursing productivity to show the complexity of the concept and its
      measurement. We then show how the concept analysis was used to design a method
      for measuring nursing productivity. Third, we describe how we used this measure
      in a pilot study of the impact of a differentiated Registered Nurse (RN) practice
      model on productivity. Finally, we identify the challenges encountered and
      present recommendations for nurse executives and researchers based on our
      findings. RATIONALE: We believe our experience can be useful to nurse executives
      and researchers who are interested in studying the impact of care delivery models
      on nursing productivity. DESIGN: We defined productivity as the ratio of output
      (patient care hours per patient day) to input (paid salary and benefit dollars).
      We conducted a pilot test using the productivity measure developed from the
      concept analysis to determine the effects of a differentiated RN practice model
      on patient, staff, and organizational outcomes. The purpose of the pilot study
      was to determine whether the data needed to measure productivity could be
      obtained from administrative databases and to develop the steps and process for
      the analysis. We analysed data by 2-week pay periods for two quarters prior to
      implementation of the differentiated nursing practice model and for two quarters
      after implementation to assess for changes in nursing productivity. RESULTS:
      Pilot testing showed that we could detect changes in productivity using this
      measurement approach. It also revealed several challenges in using administrative
      databases to measure productivity. CONCLUSIONS: We discuss these challenges with
      recommendations for both nurse executives and researchers. The most reasonable
      approach for operational decision-making is longitudinal monitoring of
      productivity by organizational units combined with indicators of quality of
      patient care.

PMID- 11985690
TI  - Expert supervisors' views of clinical supervision: a study of factors promoting
      and inhibiting the achievements of multiprofessional team supervision.
AB  - BACKGROUND: Only a few studies are available of team supervision and its
      challenges to supervisors. A multiprofessional team supervision project was
      accomplished in 1995-1998 in one university hospital in Finland. Eighty-two
      practitioners from five wards participated in the project and 10 experienced
      supervisors implemented their team supervision. AIM: The aim of this qualitative
      study is to describe the experiences of five supervisor pairs (n=10) of
      multiprofessional team supervision. METHODS: Data were collected by semi
      structured interviews from the supervisor pairs. The interviewing style was open
      and followed that of a guided conversation between supervisors and researcher.
      Interview data were analysed using thematic content analysis. FINDINGS: The
      factors that influenced team supervision were as follows: advanced knowledge of
      supervision and confidence in supervisors, commitment and motivation, interaction
      and collaborative relationships and the arrangements of team supervision. The
      positive effects of team supervision as identified by the supervisors were as
      follows: influence on interaction and human relationships in the work community,
      supervisees' strengthened professional identity and the development of
      multiprofessional practice. CONCLUSIONS: Several factors can promote or inhibit
      the achievements of team supervision. Regardless of all the difficulties related
      to team supervision, its effects on a work community are positive. For the
      supervisors, team supervision is a demanding and challenging but also a rewarding
      process.

PMID- 11985691
TI  - Predictors of nursing home placement and home nursing services utilization by
      elderly patients after hospital discharge in Taiwan.
AB  - BACKGROUND: Providing appropriate follow-up health/long-term care services after
      hospital discharge for elderly persons is important to enhance health and quality
      of life. Therefore, identifying factors that affect follow-up service utilization
      has become an important concern. Most studies of predictors of follow-up service
      utilization for elderly persons after discharge were conducted in the United
      States of America (USA). Taiwan differs substantially from the USA in health care
      system, clinical practice, case-mix, culture, and social organization; thus the
      findings from the USA need to be validated in Taiwan to ensure appropriate
      discharge referrals. AIM: To investigate pre-discharge predictors of follow-up
      care including home nursing services and nursing home placement for elderly
      patients, discharged from hospitals in Taiwan. METHODS: A prospective study with
      a case-control design was used. FINDINGS: The strongest predictors of
      institutionalization in a nursing home at 1, 3 and 6 months after discharge were
      the elderly person's pre-admission institutionalization (0.33 to 0.48) and the
      caregiver's preference for institutional displacement (0.23 to 0.85). The
      strongest predictors of use of home nursing services were the elder's self-care
      ability (0.69 to 0.76), conscious level (0.51 to 0.73), and tubes remaining
      before discharge (0.58 to 0.79). These predictors were stable at 1, 3 and 6
      months after discharge and could correctly classify 60-89% of sample.
      CONCLUSIONS: When taking nursing home and home nursing utilization into
      considerations at the same time, the elderly person's pre-admission
      institutionalization and the caregiver's preference for institutional
      displacement strongly predicted nursing home utilization after hospital
      discharge. The elder's self-care ability, conscious level, and tubes remaining
      before discharge strongly predicted the use of home nursing services after
      discharge.

PMID- 11985692
TI  - The safety and effectiveness of a nurse-led anticoagulant service.
AB  - AIM: The aim of this study was to compare the safety and effectiveness of
      anticoagulant nurses and a consultant haematologist in managing anticoagulant
      patients in a hospital outpatient setting. BACKGROUND: Nurses are increasingly
      developing roles traditionally undertaken by medical staff. As a result nurse-led
      practice has expanded in many areas including anticoagulant services. Previous
      studies have attempted to demonstrate the effectiveness of using other
      professionals to manage anticoagulant clinics over short periods of time. This
      research evaluates the safety and effectiveness of a consultant-led and a nurse
      led service over two sequential 18-month periods. RESEARCH METHODS: A
      nonexperimental design was adopted. Data were collected retrospectively, from a
      random sample of 197 patients, who had been managed by both the consultant-led
      and nurse-led service. Two main outcome measures were selected: anticoagulant
      control between professional groups and interval between outpatient clinic
      appointments. RESULTS: No statistically significant difference in anticoagulant
      control was found between professional groups (P=0.137). There was evidence that
      patients attended anticoagulant clinics on significantly fewer occasions with
      nurse-led management (P < 0.0005). CONCLUSION: At the department within which
      this research was conducted, anticoagulant nurses were found to be at least as
      safe and effective as the consultant haematologist in managing outpatient
      anticoagulant patients over the study period. These findings are of importance in
      both shaping the future provision of anticoagulant care and also contributing to
      the wider area in evaluating the impact of nurse-led practice within health care.

PMID- 11985693
TI  - Nursing staffs' perceptions of persons suffering from mania in acute psychiatric
      care.
AB  - AIM: The aim of this study was to illuminate nursing staff perceptions of persons
      suffering from mania and how this influences the provision of nursing care.
      BACKGROUND: Nursing staffs' experiential knowledge in relation to their work with
      persons with manic illness is explored, guided by a theoretical framework of
      mania as suffering. METHODS: The study was carried out with a participatory
      inquiry design, and focus group interviews were employed for the collection of
      data. The data analysis followed the qualitative content analysis procedure.
      FINDINGS: Four main themes emerged from the analysis: staff views of patients'
      self-image, needs and desires, a united stance, nursing strategies, and ethical
      dilemmas. Nursing staff discern the 'disease suffering' based on what is typical
      in the patient's behaviour, apprehend the existential suffering through the
      uniqueness of the patient's situation, and finally, realize the various ways in
      which patients can experience suffering as a consequence of nursing care and
      treatment. The findings further revealed that one of the greatest challenges of
      working with persons suffering from mania is that they are often admitted against
      their will and do not perceive themselves as being ill or in need of help.
      CONCLUSIONS: In conclusion, the findings from this study are theoretically
      transferable to similar contexts. We suggest that the themes identified above
      could be used by nursing staff to reflect on their perceptions of and encounters
      with persons suffering from mania. Furthermore, value-based psychiatric nursing
      practice, focusing on patients' experiential knowledge, is needed in order to
      assess the influence of suffering on a person's life and their experiences of
      treatment and care.

PMID- 11985694
TI  - Response to: Heartcare: an Internet-based information and support system for
      patient home recovery after coronary artery bypass graft (CABG) surgery by P.
      Flatley Brennan, S.M. Moore, G. Bjornsdottir, J. Jones, C. Visovsky and M. Rogers
      (2001) Journal Of Advanced Nursing 35, 699-708.

PMID- 11985703
TI  - Antibacterial activities and conformations of synthetic alpha-defensin HNP-1 and
      analogs with one, two and three disulfide bridges.
AB  - Structure and biological activities of synthetic peptides corresponding to human
      alpha-defensin HNP-1, AC1YC2RIPAC3IAGERRYGTC4IYQGRLWAFC5C6 with the S-S
      connectivities: C1-C6, C2-C4, C3-C5, and its variants with one, two and three
      disulfide bridges were investigated. Oxidation of synthetic, reduced HNP-1
      yielded a peptide with S-S connectivities C1-C3, C2-C4 and C5-C6, and not with
      the S-S linkages as in naturally occurring HNP-1. Selective protection of
      cysteine sulfhydryls was necessary for the formation of S-S bridges as in native
      HNP-1. Likewise, oxidation of peptide encompassing the segment from C2 to C5,
      resulted in the S-S linkages C2-C3 and C4-C5 instead of the expected linkage C2
      C4 and C3-C5. Antibacterial activities were observed for all peptides,
      irrespective of how the S-S bridges were linked. Linear peptides without S-S
      bridges were inactive. Circular dichroism (CD) spectra suggest that peptides
      constrained by one and two S-S bridges do not form rigid beta-sheet structures in
      an aqueous environment. The spectrum of HNP-1 in an aqueous environment suggests
      the presence of a beta-hairpin conformation. In the presence of lipid vesicles,
      the S-S constrained peptides tend to adopt a beta-structure. Although the S-S
      connectivities observed in HNP-1 may be necessary for other physiological
      activities, such as chemotaxis, they are clearly not essential for antibacterial
      activity.

PMID- 11985704
TI  - High-throughput peptide synthesis and peptide purification strategy at the low
      micromol-scale using the 96-well format.
AB  - The increasing demand for short- and medium-sized peptides in many fields of
      biological, medical and pharmaceutical research requires optimized and
      universally applicable high-throughput synthesis and purification techniques at
      the low-micromol scale. Here, we describe a continuous peptide
      synthesis/purification approach using the 96-well format. First, a micromol scale
      peptide synthesis on resin beads was optimized on a novel miniaturized 96
      reaction vessel block employing standard Fmoc/tBu-chemistry. Almost 90% of the
      synthesized peptides contained the target sequence as the main component, as
      judged from matrix-assisted laser desorption/ionization (MALDI) mass spectra.
      Impurities were mostly related to partially protected peptides. Second, we tested
      the applicability of ion pair reversed-phase solid-phase extraction (IP-RP-SPE)
      to purify individual peptides. Depending on the length and predicted
      hydrophobicity of the peptides, elution was performed with 25 or 35% aqueous
      acetonitrile in the presence of 0.1% trifluoroacetic acid (TFA). Thus, scavengers
      used during TFA cleavage and partially protected peptides carrying very
      hydrophobic protecting groups were effectively removed. Using a narrow step
      gradient, the target peptides were even separated from deleted sequences and
      protected peptides with similar hydrophobicities. Third, we combined the micromol
      scale synthesis in the 96-well format with purification by IP-RP-SPE on a 96-well
      micro-extraction plate format. This simple, fast and parallel approach was tested
      on 12-mer and 15-mer peptides to map epitopes of T- and B-cell clones,
      respectively. Approximately 80% of all peptides were obtained at purities > 90%
      without purification by RP-HPLC. In summary, this novel approach has several
      advantages: (i) the micromol-scale reduced the cost of peptide synthesis, (ii)
      large numbers of peptides were purified faster, (iii) the volumes of eluents and
      waste were significantly reduced, and (iv) the RP-HPLC column was not
      contaminated with hydrophobic impurities.

PMID- 11985705
TI  - Modeling alternative binding registers of a minimal immunogenic peptide on two
      class II major histocompatibility complex (MHC II) molecules predicts polarized T
      cell receptor (TCR) contact positions.
AB  - Several major histocompatibility complex class II (MHC II) complexes with known
      minimal immunogenic peptides have now been solved by X-ray crystallography.
      Specificity pockets within the MHC II binding groove provide distinct peptide
      contacts that influence peptide conformation and define the binding register
      within different allelic MHC II molecules. Altering peptide ligands with respect
      to the residues that contact the T-cell receptor (TCR) can drastically change the
      nature of the ensuing immune response. Here, we provide an example of how MHC II
      (I-A) molecules may indirectly effect TCR contacts with a peptide and drive
      functionally distinct immune responses. We modeled the same immunogenic 12-amino
      acid peptide into the binding grooves of two allelic MHC II molecules linked to
      distinct cytokine responses against the peptide. Surprisingly, the favored
      conformation of the peptide in each molecule was distinct with respect to the
      exposure of the N- or C-terminus of the peptide above the MHC II binding groove.
      T-cell clones derived from each allelic MHC II genotype were found to be allele
      restricted with respect to the recognition of these N- vs. C-terminal residues on
      the bound peptide. Taken together, these data suggest that MHC II alleles may
      influence T-cell functions by restricting TCR access to specific residues of the
      I-A-bound peptide. Thus, these data are of significance to diseases that display
      genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid
      arthritis.

PMID- 11985706
TI  - Crystal structure of biphalin sulfate: a multireceptor opioid peptide.
AB  - Biphalin is a dimeric opioid peptide, composed of two tetrapeptides connected
      'tail-to-tail', that exhibits a high affinity for all three opioid receptor types
      (i.e. mu, delta and kappa). This study presents the X-ray crystal structure of
      biphalin sulfate and compares it to other opioids that interact with the same
      biological targets. Both halves of the molecule have a folded backbone
      conformation but differ significantly from one another. Residues 1-4 in biphalin,
      which compare well with the delta selective opioid peptide DADLE, fold into a
      random coil. Residues 5-8, which can be fit to the mu selective peptide D-TIPP
      NH2, exhibit a fairly normal type III' beta bend. Biphalin also exhibits
      structural similarities with two naltrexone analogs, naltrexonazine and
      norbinaltorphamine, that are specific to mu and kappa receptor sites.

PMID- 11985707
TI  - The chemical syntheses and bioactivities of novel peptide-based endothelin
      antagonists.
AB  - Endothelin antagonists, novel tripeptides containing a series of unnatural amino
      acids, were synthesized and characterized. A linear peptide BQ-485,
      perhydroazepin-1-yl-L-leucyl (1)-D-tryptophanyl (2)-D-tryptophan (3), was
      selected as the parent compound. The introduction of D-Phe derivatives into these
      peptidic ET antagonists resulted in potent activity against the contraction of
      rat aortic smooth muscles induced by ET-1 (10 nM) which activated the ET
      receptors. Among these compounds, 15 tripeptides had high enough antagonistic
      activity at the level of 10(-7) mol/L (IC50). The activity of three compounds was
      10(-6) mol/L (IC50). These HIM-CO-Leu-D-Trp-D-Phe(-R)-OH compounds as ETA
      antagonists may provide a tool for the development of therapeutic agents in the
      treatment of putative ET-1-related disorders.

PMID- 11985708
TI  - Fractionation of Escherichia coli cell populations at different stages during
      growth transition to stationary phase.
AB  - Cultures of Escherichia coli could be separated into more than 15 cell
      populations, each forming a discrete band after Percoll gradient centrifugation.
      The cell separation was found to result from the difference in buoyant density
      but not the size difference. The cell density increases upon transition from
      exponential growth to stationary phase. Exponential phase cultures formed at
      least five discrete bands with lower densities, whereas stationary phase cultures
      formed more than 10 bands with higher densities. Two molecular markers
      characterizing each cell population were identified: the functioning promoter
      species, as identified by measuring the expression of green fluorescent protein
      under the control of test promoters; and the expressed protein species, as
      monitored by quantitative immunoblotting. These findings together suggest that
      the growth phase-coupled transition of E. coli phenotype is discontinuous.

PMID- 11985709
TI  - Identification of loci critical for replication and compatibility of a Borrelia
      burgdorferi cp32 plasmid and use of a cp32-based shuttle vector for the
      expression of fluorescent reporters in the lyme disease spirochaete.
AB  - The 32kb circular plasmid (cp32) family of Borrelia burgdorferi has been the
      subject of intensive investigation because its members encode numerous
      differentially expressed lipoproteins. As many as nine different cp32s appear to
      be capable of stable replication within a single spirochaete. Here, we show that
      a construct (pCE310) containing a 4 kb fragment from the putative maintenance
      region of a B. burgdorferi CA-11.2A cp32 was capable of autonomous replication in
      both high-passage B. burgdorferi B31 and virulent B. burgdorferi 297. Deletion
      analysis revealed that only the member of paralogous family 57 and the adjacent
      non-coding segment were essential for replication. The PF32 ParA orthologue
      encoded by the pCE310 insert was almost identical to the PF32 orthologues encoded
      on the B31 and 297 cp32-3 plasmids. The finding that cp32-3 was selectively
      deleted in both B31 and 297 transformants carrying pCE310 demonstrated the
      importance of the PF32 protein for cp32 compatibility and confirmed the
      prediction that cp32 plasmids expressing identical PF32 paralogues are
      incompatible. A shuttle vector containing the CA-11.2A cp32 plasmid maintenance
      region was used to introduce green, yellow and cyan fluorescent protein reporters
      into B. burgdorferi. Flow cytometry revealed that the green fluorescent protein
      was well expressed by almost 90% of both avirulent and infectious transformants.
      In addition to enhancing our understanding of B. burgdorferi plasmid biology, our
      results further the development of genetic systems for dissecting pathogenic
      mechanisms in Lyme disease.

PMID- 11985710
TI  - The terminal proteins of linear Streptomyces chromosomes and plasmids: a novel
      class of replication priming proteins.
AB  - The chromosomes of the soil bacteria Streptomyces, unlike those of most other
      bacteria, are linear DNA molecules. Their telomeres contain long-terminal
      inverted repeats and covalently bound terminal proteins (TPs). These bacteria
      also harbour linear plasmids that share the same structural features. In this
      study, we demonstrated that the TP was covalently bound to the 5' ends as
      proposed previously. A linear plasmid with chromosomal telomeres was constructed
      and used to purify the TPs of the Streptomyces coelicolor A3(2) chromosome. A 20
      kDa protein and its 10 kDa degradation product were isolated and their sequences
      determined by mass spectrometry. The coding sequence (tpgC) was about 100 kb from
      the right end of the chromosome. Two tpg homologues were identified by sequencing
      the 50kb linear plasmid SLP2 of Streptomyces lividans: tpgSLP2 at 6 kb from the
      left end and a putative tpg pseudogene at 8 kb from the right. The latter was in
      a terminal repeat shared by the right end of SLP2 and both ends of the S.
      lividans chromosome. The lack of the typical Streptomyces codon preference in
      this open reading frame suggests that it is a pseudogene. The close physical
      linkage between the tpg genes and their cognate telomeres would favour their
      cosegregation and co-evolution. All the Tpg polypeptides are similar in length
      (184-185 amino acids) and sequences, which include a putative helix domain that
      is homologous to part of the DNA-binding 'thumb' domain of HIV reverse
      transcriptase, and a putative amphiphilic beta-sheet that may be involved in the
      observed self-aggregation of the TP and/or the proposed membrane binding.

PMID- 11985711
TI  - Functional characterization of the antagonistic flagellar late regulators FliA
      and FlgM of Helicobacter pylori and their effects on the H. pylori transcriptome.
AB  - Helicobacter pylori is thought to regulate gene expression with a very small set
      of regulatory genes. We identified a previously unannotated open reading frame
      (ORF) in the H. pylori 26695 genome (HP1122) as a putative H. pylori flgM gene
      (sigma28 factor antagonist) by a motif-based bioinformatic approach. Deletion of
      HP1122 resulted in a fourfold increase in transcription of the sigma28-dependent
      major flagellin gene flaA, supporting the function of HP1122 as H. pylori FlgM.
      Helicobacter pylori FlgM lacks a conserved 20-amino-acid N-terminal domain of
      enterobacterial FlgM proteins, but was able to interact with the Salmonella
      typhimurium sigma28 (FliA) and inhibit the expression of FliA-dependent genes in
      Salmonella. Helicobacter pylori FlgM inhibited FliA to the same extent in a
      Salmonella strain with an intact flagellar export system and in an export
      deficient strain. Helicobacter pylori FliA was able to drive transcription of
      FliA-dependent genes in Salmonella. The effects of mutations in the H. pylori
      flgM and fliA genes on the H. pylori transcriptome were analysed using whole
      genome DNA microarrays. The antagonistic roles of FlgM and FliA in controlling
      the transcription of the major flagellin gene flaA were confirmed, and two
      additional FliA/FlgM dependent operons (HP472 and HP1051/HP1052) were identified.
      None of the three genes contained in these operons has a known function in
      flagellar biogenesis in other bacteria. Like other motile bacteria, H. pylori has
      a FliA/FlgM pair of sigma and anti-sigma factors, but the genes controlled by
      these differ markedly from the Salmonella/Escherichia coli paradigm.

PMID- 11985713
TI  - Interactions of haemoglobin with the Neisseria meningitidis receptor HpuAB: the
      role of TonB and an intact proton motive force.
AB  - We have characterized the interaction of the Neisseria meningitidis TonB
      dependent receptor HpuAB with haemoglobin (Hb). Protease accessibility assays
      indicated that HpuA and HpuB are surface exposed, HpuB interacts physically with
      HpuA, and TonB energization affects the conformation of HpuAB. Binding assays
      using [125I]-Hb revealed that the bipartite receptor has a single binding site
      for Hb (Kd 150 nM). Competitive binding assays using heterologous Hbs revealed
      that HpuAB Hb recognition was not species specific. The binding kinetics of Hb to
      HpuAB were dramatically altered in a TonB- mutant and in wild-type meningococci
      treated with the protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP),
      indicating that TonB and an intact proton motive force are required for normal Hb
      binding and release from HpuAB. Our results support a model in which both HpuA
      and HpuB are required to form a receptor complex in the outer membrane with a
      single binding site, whose structure and ligand interactions are significantly
      affected by the TonB-mediated energy state of the receptor.

PMID- 11985712
TI  - Structure of the Lrp-regulated serA promoter of Escherichia coli K-12.
AB  - Expression of the Escherichia coli serA gene is activated in vivo by the product
      of the lrp gene, leucine-responsive regulatory protein (Lrp), an effect partially
      reversed by L-leucine. We show here that serA is transcribed from two promoters,
      P1 45 bp upstream of the translation start site, and P2 92 bp further upstream.
      Lrp binds to a long AT-rich sequence from -158 to -82 from the start of the
      coding region, i.e. upstream of P1 and overlapping P2. It activates transcription
      from P1 and represses expression from P2. A second regulator, cAMP/CRP, activates
      P2, an effect that is largely inhibited by Lrp, such that catabolite repressor
      protein (Crp) and Lrp are rival activators of serA transcription.

PMID- 11985714
TI  - Complex formation between activator and RNA polymerase as the basis for
      transcriptional activation by MarA and SoxS in Escherichia coli.
AB  - Transcriptional activation in Escherichia coli is generally considered to proceed
      via the formation of an activator-DNA-RNA polymerase (RNP) ternary complex.
      Although the order of assembly of the three elements is thermodynamically
      irrelevant, a prevalent idea is that the activator-DNA complex is formed first,
      and recruitment of RNP to the binary complex occurs subsequently. We show here
      that the closely related activators, MarA, SoxS and Rob, which activate the same
      family of genes, are capable of forming complexes with RNP core or holoenzyme in
      the absence of DNA. In addition, we find that the ternary MarA-DNA-RNP and SoxS
      DNA-RNP complexes are more stable than the corresponding Rob-DNA-RNP complex,
      although the binary Rob-DNA complex is often more stable than the corresponding
      MarA- or SoxS-DNA complexes. These results may help to explain certain puzzling
      aspects of the MarA/SoxS/Rob system. We suggest that activator-RNP complexes scan
      the chromosome and bind promoters of the regulon more efficiently than either RNP
      or the activators alone.

PMID- 11985715
TI  - A fadD mutant of Sinorhizobium meliloti shows multicellular swarming migration
      and is impaired in nodulation efficiency on alfalfa roots.
AB  - Swarming is a form of bacterial translocation that involves cell differentiation
      and is characterized by a rapid and co-ordinated population migration across
      solid surfaces. We have isolated a Tn5 mutant of Sinorhizobium meliloti GR4
      showing conditional swarming. Swarm cells from the mutant strain QS77 induced on
      semi-solid minimal medium in response to different signals are hyperflagellated
      and about twice as long as wild-type cells. Genetic and physiological
      characterization of the mutant strain indicates that QS77 is altered in a gene
      encoding a homologue of the FadD protein (long-chain fatty acyl-CoA ligase) of
      several microorganisms. Interestingly and similar to a less virulent Xanthomonas
      campestris fadD(rpfB) mutant, QS77 is impaired in establishing an association
      with its host plant. In trans expression of multicopy fadD restored growth on
      oleate, control of motility and the symbiotic phenotype of QS77, as well as acyl
      CoA synthetase activity of an Escherichia coli fadD mutant. The S. meliloti QS77
      strain shows a reduction in nod gene expression as well as a differential
      regulation of motility genes in response to environmental conditions. These data
      suggest that, in S. meliloti, fatty acid derivatives may act as intracellular
      signals controlling motility and symbiotic performance through gene expression.

PMID- 11985716
TI  - Lateral flagella of Aeromonas species are essential for epithelial cell adherence
      and biofilm formation.
AB  - Mesophilic Aeromonas strains express a single polar flagellum in all culture
      conditions and produce lateral flagella on solid media. Such hyperflagellated
      cells demonstrate increased adherence. Nine lateral flagella genes, lafA-U for
      Aeromonas hydrophila, and four Aeromonas caviae genes, lafA1, lafA2, lafB and
      fliU, were isolated. Mutant characterization, nucleotide and N-terminal
      sequencing demonstrated that the A. hydrophila and A. caviae lateral flagellins
      were almost identical, but were distinct from their polar flagellum counterparts.
      The aeromonad lateral flagellins exhibited higher molecular masses on SDS-PAGE,
      and this aberrant migration was thought to result from post-translational
      modification through glycosylation. Mutation of the Aeromonas lafB, lafS or both
      A. caviae lateral flagellins caused the loss of lateral flagella and a reduction
      in adherence and biofilm formation. Mutations in lafA1, lafA2, fliU or lafT
      resulted in strains that expressed lateral flagella, but had reduced adherence
      levels. Mutation of the lateral flagella loci did not affect polar flagellum
      synthesis, but the polarity of the transposon insertions on the A. hydrophila
      lafTlU genes resulted in non-motility. However, mutations that abolished polar
      flagellum production also inhibited lateral flagella expression. We conclude that
      Aeromonas lateral flagella: (i) play a role in adherence and biofilm formation;
      (ii) are distinct from the polar flagellum; (iii) synthesis is dependent upon the
      presence of a polar flagellum filament; and (iv) that the motor proteins of the
      polar and lateral flagella systems appear to be shared.

PMID- 11985717
TI  - Regulation of the bacillus subtilis ccpC gene by ccpA and ccpC.
AB  - Bacillus subtilis CcpC, a LysR-type transcriptional regulator, represses the
      transcription of genes for citrate synthase (citZ) and aconitase (citB) in
      response to citrate availability. Transcription of ccpC was shown to initiate at
      two promoters, P1, located just upstream of the ccpC gene, and P2, located within
      or upstream of the neighbouring ykuL gene. Expression from the ccpC-specific
      promoter (P1) was negatively regulated by CcpC but independent of the carbon
      source in the medium. Gel shift and DNase I footprinting experiments revealed
      that CcpC binds to an interrupted dyad sequence that surrounds the ccpC
      transcriptional start point. Transcription of ccpC from the upstream promoter
      (P2) was repressed by glucose in a CcpA-dependent manner. A putative CcpA binding
      site (cre) was identified upstream of the -35 region of the P1 promoter.
      Transcriptional fusion studies demonstrated that glucose repression of ccpC
      expression from the P2 promoter depends on this cre site. In addition, DNase I
      footprinting experiments showed that CcpA specifically binds to this cre site and
      that the introduction of mutations (cre*) into this site abolished the binding.
      These results suggest that CcpA may control CcpC synthesis by acting as a road
      block to readthrough transcription from the P2 promoter.

PMID- 11985718
TI  - LcrQ and SycH function together at the Ysc type III secretion system in Yersinia
      pestis to impose a hierarchy of secretion.
AB  - LcrQ is a regulatory protein unique to Yersinia. Previous study in Yersinia
      pseudotuberculosis and Yersinia enterocolitica prompted the model in which LcrQ
      negatively regulates the expression of a set of virulence proteins called Yops,
      and its secretion upon activation of the Yop secretion (Ysc) type III secretion
      system permits full induction of Yops expression. In this study, we tested the
      hypothesis that LcrQ's effects on Yops expression might be indirect. Excess LcrQ
      was found to exert an inhibitory effect specifically at the level of Yops
      secretion, independent of production, and a normal inner Ysc gate protein LcrG
      was required for this activity. However, overexpression of LcrQ did not prevent
      YopH secretion, suggesting that LcrQ's effects at the Ysc discriminate among the
      Yops. We tested this idea by determining the effects of deletion or
      overexpression of LcrQ, YopH and their common chaperone SycH on early Yop
      secretion through the Ysc. Together, our findings indicated that LcrQ is not a
      negative regulator directly, but it acts in partnership with SycH at the Ysc gate
      to control the entry of a set of Ysc secretion substrates. A hierarchy of YopH
      secretion before YopE appears to be imposed by SycH in conjunction with both LcrQ
      and YopH. LcrQ and SycH in addition influenced the deployment of LcrV, a
      component of the Yops delivery mechanism. Accordingly, LcrQ appears to be a
      central player in determining the substrate specificity of the Ysc.

PMID- 11985719
TI  - Novel gene products associated with NdhD3/D4-containing NDH-1 complexes are
      involved in photosynthetic CO2 hydration in the cyanobacterium, Synechococcus sp.
      PCC7942.
AB  - Cyanobacteria possess light-dependent CO2 uptake activity that results in the net
      hydration of CO2 to HCO3- and may involve a protein-mediated carbonic anhydrase
      (CA)-like activity. This process is vital for the survival of cyanobacteria and
      may be a contributing factor in the ecological success of this group of
      organisms. Here, via isolation of mutants of Synechococcus sp. PCC7942 that
      cannot grow under low-CO2 conditions, we have identified two novel genes, chpX
      and chpY, that are involved in light-dependent CO2 hydration and CO2 uptake
      reactions; co-inactivation of both these genes abolished both activities. The
      function and mechanism of the CO2 uptake systems supported by each chp gene
      product differs, with each associated with functionally distinct NAD(P)H
      dehydrogenase (NDH-1) complexes. The ChpX system has a low affinity for CO2 and
      is dependent on photosystem I cyclic electron transport, whereas the inducible
      ChpY system has a high affinity for CO2 and is dependent on linear electron
      transport. We believe that ChpX and ChpY are involved in a unique, net hydration
      of CO2 to HCO3-, that is coupled electron flow within the NDH-1 complex on the
      thylakoid membrane.

PMID- 11985720
TI  - Genetic and functional analysis of the phosphorylcholine moiety of commensal
      Neisseria lipopolysaccharide.
AB  - Phosphorylcholine (ChoP) is a common surface feature of many mucosal organisms,
      including Neisseria spp., in which it is present exclusively on pili of
      pathogenic Neisseria and on the lipopolysaccharide (LPS) of commensal Neisseria
      (Cn). Its presence in Cn has been confirmed by nuclear magnetic resonance. It
      appears that choline is the main source for the production of ChoP by Cn. We have
      sequenced a locus, containing four genes (licA-D) with 47-73% identity to the
      lic1 locus of Haemophilus influenzae (Hi) and 21-40% identity to lic genes in
      Streptococcus pneumoniae, involved in the production and incorporation of ChoP.
      The arrangement of the Cn genes and the presence of CAAT repeats, responsible for
      phase variation of ChoP expression, resemble Hi and differ from S. pneumoniae. Cn
      DNA flanking the lic locus contains genes ilvE and NMA2149 with >85% identity to
      the pathogenic Neisseria genes. However, there are no lic genes in the
      corresponding location or elsewhere in pathogenic Neisseria. This suggests either
      the loss of the locus from pathogenic Neisseria or a horizontal transfer of genes
      to Cn, perhaps from H. influenzae spp. As in Hi, ChoP enhances adherence to and
      invasion of human epithelial cells via the receptor for platelet-activating
      factor. However, ChoP expression also increases susceptibility to serum killing
      mediated by complement and C-reactive protein. Taken together, these observations
      support the hypothesis that the ability of many organisms to switch off ChoP
      expression rapidly represents an important adaptation to different environments
      encountered during the colonization/infection process and that the ChoP moiety
      apparently synthesized by distinct means in pathogenic and commensal Neisseria
      represents an advantage in the colonization properties of these bacteria.

PMID- 11985721
TI  - Differential roles of two SARP-encoding regulatory genes during tylosin
      biosynthesis.
AB  - The tylosin biosynthetic gene cluster of Streptomyces fradiae is remarkable in
      harbouring at least five regulatory genes, two of which (tylS and tylT) encode
      proteins of the Streptomyces antibiotic regulatory protein (SARP) family. The aim
      of the present work was to assess the respective contributions of TylS and TylT
      to tylosin production. A combination of targeted gene disruption, fermentation
      studies and gene expression analysis via reverse transcriptase-polymerase chain
      reaction (RT-PCR) suggests that tylS is essential for tylosin production and
      controls the expression of tylR (previously shown to be a global activator of the
      biosynthetic pathway) plus at least one other gene involved in polyketide
      metabolism or regulation thereof. This is the first demonstration of a SARP
      acting to control another regulatory gene during antibiotic biosynthesis. In
      contrast, tylT is not essential for tylosin production.

PMID- 11985723
TI  - A novel type II secretion system in Pseudomonas aeruginosa.
AB  - The genome sequence of Pseudomonas aeruginosa strain PAO1 has been determined to
      facilitate postgenomic studies aimed at understanding the capacity of adaptation
      of this ubiquitous opportunistic pathogen. P. aeruginosa produces toxins and
      hydrolytic enzymes that are secreted via the type II secretory pathway using the
      Xcp machinery or 'secreton'. In this study, we characterized a novel gene
      cluster, called hxc for homologous to xcp. Characterization of an hxcR mutant,
      grown in phosphate-limiting medium, revealed the absence of a 40 kDa protein
      found in the culture supernatant of wild-type or xcp derivative mutant strains.
      The protein corresponded to the alkaline phosphatase L-AP, renamed LapA, which is
      secreted in an xcp-independent but hxc-dependent manner. Finally, we showed that
      expression of the hxc gene cluster is under phosphate regulation. This is the
      first report of the existence of two functional type II secretory pathways within
      the same organism, which could be related to the high adaptation potential of P.
      aeruginosa.

PMID- 11985722
TI  - A cytoplasmic coiled-coil domain is required for histidine kinase activity of the
      yeast osmosensor, SLN1.
AB  - The yeast histidine kinase, Sln1p, is a plasma membrane-associated osmosensor
      that regulates the activity of the osmotic stress MAP kinase pathway. Changes in
      the osmotic environment of the cell influence the autokinase activity of the
      cytoplasmic kinase domain of Sln1p. Neither the nature of the stimulus, the
      mechanism by which the osmotic signal is transduced nor the manner in which the
      kinase is regulated is currently clear. We have identified several mutations
      located in the linker region of the Sln1 kinase (just upstream of the kinase
      domain) that cause hyperactivity of the Sln1 kinase. This region of histidine
      kinases is largely uncharacterized, but its location between the transmembrane
      domains and the cytoplasmic kinase domain suggests that it may have a potential
      role in signal transduction. In this study, we have investigated the Sln1 linker
      region in order to understand its function in signal transduction and regulation
      of Sln1 kinase activity. Our results indicate that the linker region forms a
      coiled-coil structure and suggest a mechanism by which alterations induced by
      osmotic stress influence kinase activity by altering the alignment of the phospho
      accepting histidine with respect to the catalytic domain of the kinase.

PMID- 11985724
TI  - Ribonucleoside diphosphate reductase is a component of the replication
      hyperstructure in Escherichia coli.
AB  - Although the nrdA101 allele codes for a ribonucleoside diphosphate (rNDP)
      reductase that is essentially destroyed in less than 2 min at 42 degrees C, and
      chemical inhibition of the enzyme by hydroxyurea stops DNA synthesis at once, we
      found that incubation at 42 degrees C of an Escherichia coli strain containing
      this allele allows DNA replication for about 40min. This suggests that mutant
      rNDP reductase is protected from thermal inactivation by some hyperstructure. If,
      together with the temperature upshift, RNA or protein synthesis is inhibited, the
      thermostability time of the mutant rNDP reductase becomes at least as long as the
      replication time and residual DNA synthesis becomes a run-out replication
      producing fully replicated chromosomes. This suggests that cessation of
      replication in the nrdA101 mutant strain is not the result of inactivation of its
      gene product but of the activity of a protein reflecting the presence of a
      partially altered enzyme. The absence of Tus protein, which specifically stops
      the replication complex by inhibiting replicative helicase activity, allows forks
      to replicate for a longer time at the restrictive temperature in the nrdA101
      mutant strain. We therefore propose that rNDP reductase is a component of the
      replication complex, and that this association with other proteins protects the
      protein coded by allele nrdA101 from thermal inactivation.

PMID- 11985725
TI  - Identification of N-acetylgalactosamine-containing glycoproteins PEB3 and CgpA in
      Campylobacter jejuni.
AB  - It was demonstrated recently that there is a system of general protein
      glycosylation in the human enteropathogen Campylobacter jejuni. To characterize
      such glycoproteins, we identified a lectin, Soybean agglutinin (SBA), which binds
      to multiple C. jejuni proteins on Western blots. Binding of lectin SBA was
      disrupted by mutagenesis of genes within the previously identified protein
      glycosylation locus. This lectin was used to purify putative glycoproteins
      selectively and, after sodium dodecyl sulphatepolyacrylamide gel electrophoresis
      (SDS-PAGE), Coomassie-stained bands were cut from the gels. The bands were
      digested with trypsin, and peptides were identified by mass spectrometry and
      database searching. A 28kDa band was identified as PEB3, a previously
      characterized immunogenic cell surface protein. Bands of 32 and 34kDa were both
      identified as a putative periplasmic protein encoded by the C. jejuni NCTC 11168
      coding sequence Cj1670c. We have named this putative glycoprotein CgpA. We
      constructed insertional knockout mutants of both the peb3 and cgpA genes, and
      surface protein extracts from mutant and wild-type strains were analysed by one-
      and two-dimensional polyacrylamide gel electrophoresis (PAGE). In this way, we
      were able to identify the PEB3 protein as a 28 kDa SBA-reactive and
      immunoreactive glycoprotein. The cgpA gene encoded SBA-reactive and
      immunoreactive proteins of 32 and 34 kDa. By using specific exoglycosidases, we
      demonstrated that the SBA binding property of acid-glycine extractable C. jejuni
      glycoproteins, including PEB3 and CgpA, is a result of the presence of alpha
      linked N-acetylgalactosamine residues. These data confirm the existence, and
      extend the boundaries, of the previously identified protein glycosylation locus
      of C. jejuni. Furthermore, we have identified two such glycoproteins, the first
      non-flagellin campylobacter glycoproteins to be identified, and demonstrated that
      their glycan components contain alpha-linked N-acetylgalactosamine residues.

PMID- 11985726
TI  - Identification and characterization of phage-resistance genes in temperate
      lactococcal bacteriophages.
AB  - The sie2009 gene, which is situated between the genes encoding the repressor and
      integrase, on the lysogeny module of the temperate lactococcal bacteriophage
      Tuc2009, was shown to mediate a phage-resistance phenotype in Lactococcus lactis
      against a number of bacteriophages. The Sie2009 protein is associated with the
      cell membrane and its expression leaves phage adsorption, transfection and
      plasmid transformation unaffected, but interferes with plasmid transduction, as
      well as phage replication. These observations indicate that this resistance is as
      a result of DNA injection blocking, thus representing a novel superinfection
      exclusion system. A polymerase chain reaction (PCR)-based strategy was used to
      screen a number of lactococcal strains for the presence of other prophage-encoded
      phage-resistance systems. This screening resulted in the identification of two
      such systems, without homology to sie2009, which were shown to mediate a phage
      resistance phenotype similar to that conferred by sie2009. To our knowledge, this
      is the first description of a phage-encoded super-infection exclusion/injection
      blocking mechanism in the genus Lactococcus.

PMID- 11985727
TI  - Analysis of the kefA2 mutation suggests that KefA is a cation-specific channel
      involved in osmotic adaptation in Escherichia coli.
AB  - Mechanosensitive channels play an essential role in the regulation of turgor
      pressure in bacteria. In Escherichia coli, there are multiple mechanosensitive
      channels that have been characterized genetically: MscL, YggB and KefA. In this
      report, we describe the cloning of the kefA gene, the organization of the KefA
      protein and the phenotype of a missense mutation, kefA, which affects the KefA
      mechanosensitive channel. The altered function of the channel is manifest through
      increased sensitivity to K+ during growth at low osmolarity and complete
      inhibition of growth in media containing high K+ concentrations (0.6 M) in the
      presence of betaine or proline. Growth in high Na+ medium (0.6 M NaCl plus 20 mM
      K+) is normal. Analysis of the cytoplasmic pools shows that the mutant cannot
      regulate the K+ content of the cytoplasm when grown in high K+ medium. However,
      regulation of pools of amino acids is essentially normal and the mutant can
      accumulate high pools of proline during growth inhibition. The mutant shows
      increased sensitivity to acid hypo-osmotic shock (transition from neutral to acid
      pH combined with a reduction in osmolarity). The data are consistent with
      abnormal regulation of KefA in the presence of high K+ concentrations and either
      betaine or proline.

PMID- 11985729
TI  - Clinical significance of vascular endothelial growth factor in patients with
      primary lung cancer.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is an angiogenesis factor
      closely associated with the growth and metastasis of malignant tumours.
      METHODOLOGY: In the present study, we measured plasma VEGF levels in 20 normal
      subjects (N), 35 patients with benign lung diseases (B), 28 patients with
      untreated advanced lung cancer (NT) and 10 patients with treated lung cancer (T).
      In addition, we measured the VEGF levels in pleural effusions from five patients
      with primary lung cancer and two patients with active infectious diseases.
      Vascular endothelial growth factor was measured by ELISA. RESULTS: The mean (+/
      SD) plasma VEGF level in NT patients (160.8 +/- 177.4 pg/mL) was fivefold higher
      than that in other patient groups (T, 17.7 +/- 4.9 pg/mL; B, 28.3 +/- 17.6 pg/mL)
      and the N group (14.9 +/- 7.0 pg/mL; P < 0.01). Vascular endothelial growth
      factor from lung cancer pleural effusions (17 526.0 +/- 22 498.2 pg/mL) was 25
      fold higher than that from patients with active infectious diseases (665.5 +/-
      259.0 pg/mL). CONCLUSIONS: Plasma VEGF may be a good clinical indicator for the
      assessment of primary lung cancer and pleural effusion VEGF in primary lung
      cancer is higher than pleural effusion VEGF in patients with inflammatory
      diseases.

PMID- 11985730
TI  - Serum vascular endothelial growth factor levels correlate better with tumour
      stage in small cell lung cancer than albumin, neuron-specific enolase or lactate
      dehydrogenase.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is an important cytokine in
      the process of angiogenesis. Elevated serum levels of the cytokine may determine
      cancer patients who will benefit from adjuvant anti-angiogenic therapy in the
      future. To correlate serum levels of VEGF with tumour stage and established
      prognostic markers in patients with small cell lung cancer (SCLC), a prospective
      study was performed on 70 patients. METHODOLOGY: From August 1999 to May 2000, 70
      consecutive patients (51 male, 19 female) with histologically proven SCLC were
      enrolled into the study. Staging of the disease included clinical investigation,
      bronchoscopy, chest X-ray, thoracic computed tomography and ultrasound. The
      patients were grouped into five stages according to the Marburg classification
      (very limited disease (VLD), limited disease (LD), extensive disease I (EDI),
      extensive disease II (EDII) and extensive disease III (EDIII)). Prior to
      treatment, a 10 mL serum sample from each patient was examined by ELISA to
      quantify levels of VEGF and neuron-specific enolase (NSE). Lactate dehydrogenase
      (LDH) and albumin levels were determined by photomorphometric analysis.
      Statistical analysis was performed using the Waller-Duncan k ratio t-test and
      Pearson's correlation test. RESULTS: Serum VEGF levels correlated well with
      tumour stage (P < 0.0001). Albumin levels were not correlated with tumour stage,
      but levels of NSE and LDH increased with stage progression. When patients were
      divided into two groups (VLD and LD vs EDI-III), VEGF levels were significantly
      lower in the initial stages of the disease compared with extensive disease (P <
      0.0001). Serum levels of VEGF correlated better with tumour stage than did
      concentrations of NSE, LDH or albumin. CONCLUSION: Serum VEGF levels may serve as
      an additional prognostic marker in the course of patients with SCLC. Further
      studies are needed to determine whether these patients may benefit from
      additional anti-angiogenic therapy in the future.

PMID- 11985731
TI  - Cyclic stretch upregulates interleukin-8 and transforming growth factor-beta1
      production through a protein kinase C-dependent pathway in alveolar epithelial
      cells.
AB  - OBJECTIVE: Positive-pressure mechanical ventilation can injure the lung, causing
      oedema and alveolar inflammation, which is termed 'ventilator-induced lung
      injury' (VILI). We postulated that cyclic stretch upregulates the release of
      cytokines, which may cause lung damage, and explored which cytokines were
      released after cyclic stretch in type II alveolar epithelial cells (A549).
      METHODOLOGY: To test this hypothesis, A549 cells were cultured on a silicoelastic
      membrane and interleukin (IL)-1beta, IL-8, granulocyte-macrophage colony
      stimulating factor, activin, transforming growth factor (TGF)-beta1, insulin-like
      growth factor-2 and tumour necrosis factor-alpha mRNA and protein were assessed
      after stimulation of the cells by cyclic stretch. RESULTS: Cyclic stretch induced
      activation of protein kinase C and resulted in the release of IL-8 and TGF-beta1
      from A549 cells. CONCLUSIONS: The release of IL-8 and TGF-beta1 from alveolar
      epithelial cells may be a contributing factor in alveolitis associated with VILI.

PMID- 11985732
TI  - Optimization of sputum-processing methods for the measurement of interleukin-5:
      effects of protease inhibition.
AB  - BACKGROUND: Interleukin (IL)-5 measurement in sputum samples has produced
      variable results that appear to be due to methodological problems. The aim of the
      present study was to investigate the effects of dithiothreitol (DTT), sputum
      protease inhibition and sample storage on IL-5 recovery in order to develop a
      method to accurately measure IL-5 in dispersed sputum supernatant. METHODOLOGY:
      Measurement of IL-5 in sputum was performed in 22 subjects with airway disease.
      Interleukin-5 recovery was measured in samples spiked with recombinant human IL-5
      using a commercial ELISA. A mix of four protease inhibitors (PI) was added to
      sputum processed using the selection method with dispersion using DTT and stored
      with and without inhibitors. RESULTS: The addition of PI to sputum resulted in a
      24% increase in IL-5 recovery. Recovery was not further increased with the
      addition of a blocking protein. Storage of IL-5-spiked sputum gave significantly
      less recovery. The addition of PI to sputum processed with DTT had no effect on
      total cell count, viability or cell differential. CONCLUSION: Interleukin-5
      recovery is increased by the addition of PI to samples processed using the
      selected portion method with DTT dispersion. A protease inhibitor cocktail should
      be added to sputum for IL-5 assay.

PMID- 11985733
TI  - Use of star volume to measure the size of the alveolar space in the asthmatic
      guinea-pig lung.
AB  - BACKGROUND: The ovalbumin-sensitized guinea-pig is a useful small-animal model of
      allergic asthma; however, it is unclear whether considerable morphological
      changes occur in the lung. METHODOLOGY: Guinea-pigs were initially given
      ovalbumin (i.p. injection) for 14 days and asthma was then induced by daily
      challenges with aerosolized ovalbumin for 10 days. During this time, animals were
      treated with either saline (positive control) or dexamethasone. Pulmonary
      sections were prepared to estimate the volume and surface area of the alveolar
      space, mean thickness of the alveolar septum and star volume of the alveolar
      space using stereological methods. RESULTS: The primary change in the lung in the
      positive control group was a significantly increased star volume, which was
      approximately threefold that of animals not treated with ovalbumin and the
      dexamethasone-treated group. There were no significant differences in other
      morphometric parameters between the groups. CONCLUSION: Star volume of the
      alveolar space appears to be a good and useful parameter to detect morphological
      changes of the asthmatic lung.

PMID- 11985734
TI  - Comparison between specified percentage and fifth percentile criteria for
      spirometry interpretation in Thai patients.
AB  - OBJECTIVES: The present study was conducted to determine the degree of agreement
      between the interpretation of spirometry using a specified percentage of
      predicted value (SPC) and the fifth percentile (FPC) as the cut off between
      normal and abnormal. METHODOLOGY: Spirometric values were collected for 1754
      subjects attending the respiratory service at Siriraj Hospital between February
      2000 and April 2001. These values included forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV1), FEV1/FVC, maximal mid-expiratory flow (FEF25
      75%) and peak expiratory flow (PEF). A comparison of results between SPC and FPC
      was performed. The SPC cut-off values for FVC, FEV1, FEV1/FVC, FEF25-75% and PEF
      were 80% predicted, 80% predicted, 70%, 65% predicted and 80% predicted,
      respectively. The FPC cut-off values were calculated from reference equations for
      the Thai population. Inter-rater agreement was calculated as the kappa score.
      RESULTS: High kappa scores were obtained for FVC (0.84), FEV1 (0.88) and FEF25
      75% (0.80). However, poor agreement was found for FEV1/FVC (0.72) and PEF (0.61).
      When the cut-off values for SPC were modified to 90% of predicted values for
      FEV1/FVC and to 65% of predicted values for PEF, agreement was substantially
      improved to 0.92 and 0.89, respectively. CONCLUSIONS: Interpretation by SPC using
      cut-off values of 80% predicted for FVC and FEV1 and 65% predicted for FEF25-75%
      resulted in good agreement with FPC. However, the SPC cut-off values for FEV1/FVC
      and PEF should be modified to 90% predicted and 65% predicted, respectively.

PMID- 11985735
TI  - Prevalence of self-reported respiratory symptoms in rural areas of Iran in 2000.
AB  - OBJECTIVES: The aims of the present study were to measure the population
      prevalence of symptoms of asthma, chronic bronchitis, obstructive lung disease
      and non-specific respiratory symptoms in randomly selected rural communities in
      south-west Isfahan, Iran. METHODOLOGY: Nine hundred and ninety-four subjects from
      a total of 1127 villagers (88.2% response rate) took part in a medical interview
      conducted by interns from the Isfahan Medical School. RESULTS: The mean (+/-SD)
      age of the population surveyed was 25.21 +/- 17.55 years and the smoking rate was
      7.2%. The self-reported prevalence rates for current asthma, chronic bronchitis,
      non-specific exercise-induced cough and night cough were 6.1, 4.4, 13.3 and
      11.3%, respectively. CONCLUSION: Asthma, chronic bronchitis and other respiratory
      disorders in rural Isfahan are more prevalent than expected for a young rural
      population with low smoking rates. The cause of this should be investigated.

PMID- 11985736
TI  - Adherence to asthma self-management plans with inhaled corticosteroid and oral
      prednisone: A descriptive analysis.
AB  - BACKGROUND: Asthma self-management plans (SMP) are widely recommended for use,
      but there is little information regarding the degree of patient adherence to
      their instructions. The aim of the present study was to perform a descriptive
      analysis of patient responses to worsening asthma with regard to using
      individualized SMP. METHODS: Diary data were obtained from an earlier 2 year
      study in which patients used regularly revised SMP in combination with daily
      recordings of peak expiratory flow (PEF) and symptoms to manage intercurrent
      asthma episodes. Based on PEF and symptom changes, the SMP contained instructions
      about increasing the dose of inhaled corticosteroid (ICS) or commencing oral
      prednisone during worsening asthma, depending on severity. Data from 165 patient
      diaries were analysed. First, documented responses to episodes of worsening
      asthma were matched against SMP instructions and adherence was determined using a
      priori criteria. Second, each occasion when the ICS dose was increased or
      prednisone was commenced was identified and changes in PEF and/or symptoms that
      may have led to these actions were sought. RESULTS: Adherence for increasing the
      ICS dose was dependent on asthma severity, ranging from 78% during severe
      episodes to 31% during mild short-lived events. When oral prednisone was
      indicated, patients were adherent on 56% of occasions. Symptoms prompted
      intervention more frequently than changes in PEF. Significant changes in PEF were
      absent on 41 and 48% of occasions for ICS dose increase and oral prednisone use,
      respectively. CONCLUSIONS: Adherence to asthma SMP is variable and often poor. It
      tends to increase in proportion to the severity and duration of an asthma
      episode. This underscores the importance of SMP in more severe asthma. Symptoms
      are more important then PEF in prompting patients to alter treatment. This ought
      to modify our approach in constructing individual asthma SMP.

PMID- 11985737
TI  - Chronic cough at a non-teaching hospital: Are extrapulmonary causes overlooked?
AB  - OBJECTIVE: To estimate the prevalence, assess the diagnostic approach and to
      identify specific causes and treatment response of chronic persistent cough (CPC)
      in consecutive adult patients attending the chest clinic at a non-teaching
      hospital in Riyadh, Saudi Arabia. METHODOLOGY: Chronic persistent cough was
      defined as cough persisting for more than 3 weeks. Patients were assessed
      clinically and investigated according to the suspected diagnosis. The specific
      causes were confirmed by appropriate investigations, as well as response to
      specific therapy. Improvement in cough following therapy was assessed
      subjectively by patients on a scale from 0 to 100%. RESULTS: Of 1332 patients
      seen in the chest clinic, 136 (10.2%; 95% confidence interval 8.6-11.8%)
      presented with CPC as the main complaint. One hundred patients (55% males) were
      assessed, after excluding 36 patients who were lost to follow up. The common
      presenting diagnoses (for the 81 patients who had previously consulted a
      physician) were upper respiratory tract infection (17.1%), asthma (15.9%),
      bronchitis (9.8%) and unknown in 30.8% of patients. Final diagnoses (as a sole or
      contributory cause) were established in 96% of patients and included
      rhinosinusitis (RS; 60%), asthma (26%), gastro-oesophageal reflux (GERD; 9%),
      postinfectious cough (8%) and bronchiectasis (5%). The agreement between the
      presenting and final diagnoses was generally poor, especially for extrapulmonary
      causes, which was as low as 5.3%. All patients, except for one, had complete or
      substantial improvement in the severity of cough. CONCLUSIONS: In a non-teaching
      hospital setting, CPC is a common benign disorder that rarely requires
      specialized investigations and is easily treated once the causes are identified.
      The multiplicity of causes and extrapulmonary triggers of CPC, particularly RS,
      are often overlooked. The principal causes in our series remain the same as in
      studies elsewhere, namely RS, asthma and GERD.

PMID- 11985738
TI  - Are you busy for the next 5 years? Recruitment in the Childhood Asthma Prevention
      Study (CAPS).
AB  - OBJECTIVE: The process of recruitment into randomized controlled trials is not
      often reported. In the present paper, the methods used for recruitment into the
      Childhood Asthma Prevention Study are reported and the reasons why eligible
      subjects chose not to participate or withdrew from the trial are examined.
      METHODOLOGY: Recruitment was conducted at the antenatal clinics of six hospitals
      in Sydney (NSW, Australia). Pregnant women with a family history of asthma who
      consented to participate were randomized into one of four groups and were asked
      to follow a set of interventions. The study will continue until the infants are 5
      years old. RESULTS: Of 7171 women screened, 2095 (29.2%) were eligible, of whom
      only 616 (29.4% of eligible women) were recruited. The main reasons for not
      taking part in the study were a lack of interest, ineligibility (on further
      questioning), inability to be contacted and 'too busy'. During the first 21/2
      years of the trial, 10% of participants withdrew. The most common reasons for
      withdrawal from the study were loss of contact, family moving interstate or
      overseas and medical reasons. In families that withdrew from the trial or who
      were eligible but did not participate, the parents were significantly younger,
      mothers were less educated and fathers were less likely to be in full-time
      employment. CONCLUSIONS: By collecting demographic data on people who withdrew
      from the study and chose not to participate, we gained a better understanding of
      why our recruitment rate was low. The preferential recruitment of some sectors of
      the community has important implications for the ways in which future studies
      will be planned.

PMID- 11985739
TI  - An inverse correlation between estimated tuberculosis notification rates and
      asthma symptoms.
AB  - BACKGROUND: A recent ecological analysis demonstrated a strong inverse
      relationship between tuberculosis notification rates and the prevalence of asthma
      symptoms in 13-14-year-old children as obtained from the International Study of
      Asthma and Allergies in Childhood (ISAAC). However, the analysis was confined to
      the 23 countries in which the tuberculosis notification rates were considered to
      be of sufficient validity. METHODS: A similar analysis was performed using
      estimated tuberculosis incidence rates obtained from the World Health
      Organization Global Tuberculosis Programme and asthma symptom prevalence data
      from ISAAC for both the 6-7 and 13-14 years age groups in 38 and 55 countries,
      respectively. RESULTS: For the 6-7-year-old children, there was a significant
      inverse relationship between estimated tuberculosis incidence and the prevalence
      of key asthma symptoms. However, in the 13-14 year age group, a significant
      inverse relationship was only demonstrated for 'asthma ever'. CONCLUSION: The
      present study extends the inverse relationship between tuberculosis rates and
      asthma prevalence to the 6-7-year-old age group and suggests that the
      association, if causal, may be stronger at this younger age.

PMID- 11985740
TI  - Diffuse alveolar haemorrhage: a rare reaction to insect sting.
AB  - Insect stings and subsequent reactions are common occurrences, but life
      threatening systemic reactions are rare. Herein, we describe the case of a young
      man who developed diffuse pulmonary haemorrhage following an insect sting. He had
      experienced urticarial reactions to insect stings previously. Diffuse pulmonary
      haemorrhage should be recognized as an uncommon manifestation of severe systemic
      reaction to insect sting.

PMID- 11985741
TI  - Spontaneous bilateral rupture of the Achilles tendon in a patient with chronic
      obstructive pulmonary disease.
AB  - A 69-year-old man with chronic obstructive pulmonary disease (COPD) presented
      with an exacerbation of cough and breathlessness, as well as a 5 day history of
      sudden-onset bilateral calf tenderness. He had been commenced on inhaled steroids
      41/2 years earlier and then received maintenance oral prednisone. Upon
      examination, there was a haematoma inferior to the medial malleolus with no
      Achilles tenderness on the left side. On the right side, there was focal
      tenderness over the mid-portion of the Achilles tendon with pain accentuated upon
      dorsi flexion. A venous duplex study confirmed superficial venous thrombosis
      involving the left gastrocnemius vein extending proximally to the popliteal vein
      junction. The major axial deep veins of the left lower leg were patent. Findings
      on the right side were normal. A subsequent diagnostic ultrasound demonstrated
      unequivocal bilateral Achilles tendon ruptures. The patient subsequently
      underwent corrective surgery. There have been several reports of bilateral
      Achilles tendon rupture associated with long-term corticosteroid use. It is
      likely that this entity is underdiagnosed because of a lack of awareness of this
      association by physicians. Recognition and surgical intervention are likely to
      reduce morbidity and improve outcome.

PMID- 11985743
TI  - Effects of an implemented care policy on patient and personnel experiences of
      care.
AB  - A care policy was implemented within health care in the county of Vasterbotten,
      Sweden. A questionnaire was administered before and after the implementation of
      the care policy to assess its effects. Patients within hospital care and primary
      health care described their experiences in a base-line study (n=3950) in 1994 and
      a follow-up study (n=2941) in 1996. On the same occasions personnel (n=2362 and
      2310, respectively) answered the same questionnaire assessing what they thought
      their patients experienced. No significant positive effects of the implementation
      were seen by the patients. Fewer patients felt that they were understood when
      they talked about their problems, dared to express criticism or denied they were
      treated nonchalantly in the follow-up study. The experiences of the personnel
      were in line with those of the patients concerning nonchalant treatment in the
      follow-up study. Furthermore, fewer staff members thought that their patients
      felt they had adequate help with hygiene whilst more thought that their patients
      felt they were responded to in a loving way. One interpretation of the negative
      outcome is that organizational changes, strained resources and cuts in staffing
      during the 90s may have reduced the possibility of integrating the care policy in
      spite of an ambitious and extensive intervention.

PMID- 11985744
TI  - Professional carers' struggle to be confirmed. Narratives within the care of the
      elderly and disabled.
AB  - Twenty-seven members of staff working in special types of housing in Sweden
      narrated 95 narratives about their experience of being in problematic situations
      during the working day. The narratives were interpreted using a phenomenological
      hermeneutic approach inspired by the philosophy of Ricoeur. The narratives mainly
      concerned interactions with colleagues and very few narratives concerned
      interactions with residents and relatives. On the relationship level of
      communication there is evidence that many interactions among the staff, residents
      and relatives were of a receptive and disconfirming nature. The results indicate
      that the staff feel lonely, and struggled to maintain self-esteem and to be
      confirmed.

PMID- 11985745
TI  - Gender bias in nursing care? Gender-related differences in patient satisfaction
      with the quality of nursing care.
AB  - Gender-related differences in experience with nursing care, was studied using
      data from a Norwegian survey of patient-satisfaction. The survey included 1469
      male and 1226 female patients. Results showed that young female patients were
      less content with all aspects of nursing care when compared with young male
      patients. Female patients experienced, quite contrary to their male counterparts,
      that the nursing staff was less committed and caring, has less time and was less
      skilled. The young women were also less content with what they felt was a lack of
      opportunity to provide the staff with information they believed to be important
      to their condition or ailment. Analysis also revealed that female patients,
      compared with their male counterparts, indicated a higher score on the subjective
      importance of the different aspects of care. These findings are discussed on the
      basis of gender-related research in general. The finding of lower satisfaction
      amongst younger female patients could be ascribed to the power-balance between
      nursing staff and patients. The discussion shows, however, that there are a
      number of possible interpretations as to why female patients are less content
      with nursing care compared with male patients. As the reasons for the findings
      may be derived from several sources it becomes evident that there is a need for
      further research using alternative approaches.

PMID- 11985746
TI  - Disabled children's perceptions of technical aids, assistance and peers in play
      situations.
AB  - The purpose of the study was to gain a deeper understanding of how children with
      disabilities perceive their technical aids in play situations. Transcribed
      interviews with eight children with disabilities were analysed according to the
      constant comparative method of grounded theory described by Glaser & Strauss.
      Three categories were found in the data, forming a model describing the child's
      relations in play situations (core category): to technical aids, to assistance
      and to the play environment. Two of the categories included relations to adults.
      The children's opportunities to play required that a parent or an assistant be
      present. Access to the playground also required the assistance of adults. The
      third category, relation to technical aids, is an individual one, as the
      technical aids were perceived differently by all the children. The technical aids
      were also seen as an extension of the child. The implications for parents and
      service providers are discussed.

PMID- 11985747
TI  - Long-term increase in quality of nursing documentation: effects of a
      comprehensive intervention.
AB  - This study aimed to evaluate the longitudinal effects of a nursing-documentation
      intervention on the quantity and quality of the nursing documentation in a sample
      of patient records at a university hospital in Stockholm, Sweden. In this quasi
      experimental longitudinal study, two hospital wards participated in a 2-year
      intervention and a third ward was used for comparison. The intervention consisted
      of organizational changes and education regarding nursing documentation in
      accordance with the VIPS model, a model designed to structure nursing
      documentation. To evaluate the effect, patient records were audited at three
      different time points: before the intervention, directly after the intervention
      and 3 years after the intervention. A total of 269 patient records were used. The
      findings showed a significant score increase in quantity as well as in quality of
      the nursing documentation, in the intervention wards directly after the
      intervention, as compared with those from the comparison ward. The results
      suggests that a comprehensive intervention based on the VIPS model and including
      organizational support for registered nurses (RN) may improve nursing
      documentation in an acute care hospital setting.

PMID- 11985748
TI  - Struggling to be/show oneself valuable and worthy to get care. One aspect of the
      meaning of being dependent on care--a study of one patient, his wife and two of
      his professional nurses.
AB  - Dependency on care has commonly been described negatively and as a problem that
      needs to be addressed. From a larger data material, interviews with an old,
      hospitalized man with a chronic disease, his wife and two of his professional
      nurses was selected to study. The aim was to illuminate the meaning of being
      dependent on care, when it appears "negative". A phenomenological-hermeneutic
      approach was used to interpret the material. The interpretation shows that
      dependency on care is reluctantly shown although it is expected to be expressed
      and/or respected as it is shown. This makes dependency on care camouflaged and
      the space to be dependent is limited. The meaning of being dependent on care is
      understood as a two-dimensional struggle for existence. One dimension of the
      struggle is about to be/show oneself worthy to get care, as dependency on care
      holds a fear to be abandoned. The other dimension of the struggle is about to
      be/show oneself valuable as a human being, as identity is built upon being able
      to manage oneself and be strong. The interpretation if reflected on can open up
      possibilities to improve the quality of life for patients who are dependent on
      care.

PMID- 11985749
TI  - Organization, work and work reactions: a study of the relationship between
      organizational aspects of nursing and nurses' work characteristics and work
      reactions.
AB  - This article describes a quantitative, correlational study of the relationship
      between organizational aspects (such as the predictability of the care), work
      characteristics (autonomy and workload) and work reactions (work satisfaction and
      health complaints) in nursing work. The variables have been measured by
      questionnaires. Subjects were 155 nurses from nine units in two general hospitals
      in the Netherlands. Several organizational aspects seem to be correlated with
      work characteristics and work reactions. Organizational aspects particularly
      influence work characteristics and play, therefore, a mediating role in the
      relationship between organizational aspects and work reactions. Job satisfaction
      is not only correlated with the autonomy, but also with workload. Health
      complaints appeared to be mainly correlated with the workload. It is concluded
      that for an improvement of job satisfaction and reduction of health complaints,
      it is not only necessary to improve autonomy and reduce workload, but also to pay
      attention to organizational aspects because these may influence the work
      characteristics.

PMID- 11985750
TI  - Life situation and function in elderly people with and without leg ulcers.
AB  - The majority of elderly patients with leg ulcers live at home and receive
      treatment for their ulcers within the primary health care system. Little is known
      about the patients' ability or behaviour in the life situation and how well they
      manage their daily life at home. The Philadelphia Geriatric Center Multilevel
      Assessment Instrument (PGC MAI) was used to assess and compare the life situation
      in 70 patients (mean age 79 +/- 6.5 years) with leg ulcers and in 74 elderly
      persons (mean age 80 +/- 5.7 years) without leg ulcers. The patients with leg
      ulcers had significantly lower mean values in the domains of physical health,
      activity of daily living (ADL), cognition, time use and social behaviour,
      personal adjustment and environmental quality than those without ulcers. Sixty
      three percent of the patients reported ulcer-related pain, and all of them were
      dependent on health care personnel for dressing changes. This may indicate that
      the life situation among elderly persons with leg ulcers is not so good as
      compared with that of elderly persons without ulcers and that patients with leg
      ulcers are more vulnerable than elderly people of the same age.

PMID- 11985751
TI  - Incidence of violence towards staff caring for the elderly.
AB  - A survey study concerning violence was conducted among staff (n=506) working with
      the elderly in residential settings and ordinary homes. The major aim of the
      study was to investigate the incidence of violence directed towards staff by
      elderly people living in residential settings. Furthermore, associations between
      the number of violent incidents and gender, age, year in service, year at present
      place of work, education of the staff, type of setting, the frequency and type of
      violence as well as the emotional reactions expressed by the staff should be
      examined. Forty percent of the staff was exposed to violence during the preceding
      year and 18% noted incidents of violence daily. A significantly larger proportion
      of staff working in nursing homes registered violence compared with those working
      in other types of settings. Physical violence was the most common (76%) type of
      violence. Powerlessness, sadness, anger and feelings of insufficiency were the
      most dominant feelings among staff facing by violent situations. Our results
      point to the necessity to further study caregivers' perception of patient
      violence and its impact on the quality of care.

PMID- 11985752
TI  - Asthma nurse practice improves outcomes and reduces costs in primary health care.
AB  - OBJECTIVE: The aim of this study was to elucidate the care of patients with
      asthma in primary health care from medical, patient self-management, health,
      quality of life, and health economic perspectives. METHODS: Asthma nurse practice
      (ANP), an alternative asthma self-management strategy, was compared with
      traditional asthma care in primary health care in southern Sweden regarding
      medical history, lifestyle, self-management, symptoms caused by asthma, effects
      on sick leave, state of health, quality of life and health care costs. The first
      part of the investigation comprised a retrospective study of a randomly selected
      sample of patient records of asthmatics (n=152). The second part, lasting 3
      months, was prospective and included consecutive patients visits (n=347).
      RESULTS: The ANP approach showed better results in most of the evaluated outcomes
      such as asthma quality documentation and self-management and the number of asthma
      symptoms was significantly lower. From a health economic perspective the results
      were encouraging with respect to ANP. CONCLUSION: This alternative asthma
      strategy, ANP, improved asthma care in primary health care and resulted in
      economic advantages in the health care sector. However the result may only be
      generalized to other practices working with asthma nurses in the same way.

PMID- 11985753
TI  - Nurses' experiences of abusive/non-abusive caring for demented patients in acute
      care settings.
AB  - Nurses caring for patients with dementia in acute care settings often lack
      specialized education in geriatric nursing. The acute care settings do not have
      an environment made for dementia care. The staff often had a high workload, which
      makes the situation stressful and the nurses who take care of these patients
      might end up in difficult situations. The aim of this study was to describe
      nurses' experiences of difficulties related to caring for patients with dementia
      in acute care settings. Interviews were performed with 12 nurses. Qualitative
      thematic content analyses were carried out in several steps. The results show
      that the nurses experienced various difficulties in meeting patients with
      dementia in acute care settings. This gave rise to for example frustration. Most
      commonly reported was lack of time to treat these patients satisfactorily. The
      difficulties were mostly related to the often disorderly conduct of these
      patients, the ethical problems that appeared in the care of these patients, and
      the medical care organization. The problematic situations described sometimes led
      to abuse and neglect of these patients.

PMID- 11985754
TI  - Body mass index, weight loss and energy intake of old Danish nursing home
      residents and home-care clients.
AB  - Low body mass index (BMI) and weight loss is common among old home-care clients
      and nursing home residents in many countries - often in spite of an apparent
      sufficient intake of energy. The aim of this study was to assess whether a
      similar problem exists in Denmark. Information regarding height, body weight,
      BMI, and energy intake was collected. Besides this, 24 residents were weighed
      regularly during 1 year. The study was carried out in five nursing homes and two
      home-care districts situated in the area of Copenhagen. A total of 180 residents
      and 200 clients 65+ years of age participated. Main outcome measures were
      prevalence of BMI < 20 kg/m2, BMI < 18.5 kg/m2, acute weight loss and median
      energy intake. Thirty-three and thirty per cent of the residents and clients had
      a BMI < 20 kg/m2 and, 22 and 12% had a BMI < 18.5 kg/m2. Of the residents, who
      were weighed regularly, 38% had a weight loss above 5%. The median intake of
      energy was equal to or above the estimated median energy requirement. Hence, the
      prevalence of low BMI and weight loss among old Danish nursing home residents and
      home-care clients is high and similar to that found in other countries. There is
      a need for increased focus on nutritional state and risk factors in these
      settings.

PMID- 11985755
TI  - Colour perception among the very elderly related to visual and cognitive
      function.
AB  - Colour perception was studied among a representative sample of 95-year olds and
      compared with previously examined 80-year olds and a group with Alzheimer's
      disease (AD), mean age of 80 years. The 95-year olds' results were on a
      significantly lower level than the other two groups but showed a similar pattern
      as to colour -discrimination, -naming, -preferences and colour/form recognition.
      Visual function among 95-year olds had only minor influence on their result in
      contrast to cognitive function which had a more profound impact. Most
      interestingly though, the subjects with Alzheimer's diagnosis, younger than the
      95-year olds but with a conclusive diagnosis of dementia, performed on an overall
      higher level than the 95-year olds. This advantage for the Alzheimer group
      remained even when compared with a sub sample of the 95-year olds with possible
      dementia diagnosis excluded. On the other hand, only including 95-year olds with
      a Mini Mental Examination score of >26 in comparison with the Alzheimer group
      made the differences between the two groups disappear. It is suggested that
      colour perception as measured in this study is well preserved throughout life.
      The overall lower colour perception ability in 95-year olds compared with both 80
      year olds and subjects with AD may be an expression of the complexity of very
      high age rather than any isolated concomitant factor.

PMID- 11985756
TI  - The meaning and form of occupational therapy as experienced by women with
      psychoses. A phenomenological study.
AB  - The meaning and form of occupational therapy as experienced by women with
      psychoses: a phenomenological study The aim of this study was to illuminate the
      experiences of occupational therapy interventions in individuals with psychoses.
      Repeated tape-recorded narrative interviews were conducted with six women
      participating in occupational therapy immediately after an intervention. The
      subsequent analyses followed a phenomenological approach. Key constituents
      integrated in two structures, are the main findings. The meaning of occupational
      therapy as expressed in the key constituents relief, self-knowledge, belief in
      the future, capability, resistance and satisfaction formed one structure. The
      form of occupational therapy as expressed in the key constituents time,
      environment, guidance, voluntariness and collaboration represented the other
      structure. These findings confirm and give empirical support to beliefs and
      assumptions expressed in occupational therapy literature. The results form a
      conceptual base for developing an evaluative assessment instrument for
      individuals with psychoses participating in occupational therapy.

PMID- 11985758
TI  - Ultrasonography, exploration of human muscle-tendon function.

PMID- 11985759
TI  - Measurement of viscoelastic properties of tendon structures in vivo.
AB  - The purpose of this study was to investigate the viscoelastic properties of
      tendon structures in humans. Elongation of the tendon and aponeurosis of medial
      gastrocnemius muscle (MG) was directly measured by ultrasonography, while
      subjects (n=19) performed ramp isometric plantar flexion up to the voluntary
      maximum, followed by a ramp relaxation. The relationship between tendon
      elongation (L) and estimated muscle force (Fm) was fitted to a linear regression,
      the slope of which was defined as compliance of the tendon structures. The
      hysteresis was calculated as the ratio of the area within the L-Fm loop (elastic
      energy dissipated) to the area beneath the load portion of the curve (elastic
      energy input). The resulting L-Fm relationship was non-linear in form, as
      previously reported on animal and human tendons in vitro. The mean compliance was
      4.5+/-1.1. 10-2 mm/N. However, there was a considerable inter-subject variability
      (2.9 to 7.2. 10-2 mm/N). The Young's modulus, i.e., the slope of the stress
      strain curve, was 280 MPa, which tended to be lower than the previously reported
      values for human tendons. It was also found that the strain of the tendon
      structures was homogeneously distributed along their length. The mean hysteresis
      (energy dissipation) was 22.2+/-8.8%. However, again there was a considerable
      inter-subject variability (9.7 to 37.2%). The present results indicated that the
      tendon structures of human MG were considerably compliant and their hysteresis
      was in accordance with previously reported values.

PMID- 11985760
TI  - Calf muscle function after Achilles tendon rupture. A prospective, randomised
      study comparing surgical and non-surgical treatment.
AB  - In a prospective, randomised, multicentre study, 112 patients with Achilles
      tendon rupture (ATR) were allocated to surgical treatment (n=59), followed by
      early functional rehabilitation using a brace, and non-surgical treatment (n=53),
      i.e. eight weeks of plaster treatment. In this study, the results of the
      isokinetic muscle strength evaluation are presented for contractions in both the
      concentric and the eccentric mode, plantar flexion and dorsiflexion, two angular
      velocities and three different positions of the subject. The heel-raise test for
      endurance, maximum calf circumference and tendon width were also evaluated. The
      re-rupture rate was 20.8% in the non-surgically-treated group and 1.7% in the
      surgically-treated group. No significant differences were found between the
      treatment groups in terms of the isokinetic strength measurements and the
      endurance test among the patients who did not sustain a re-rupture. If a re
      rupture is avoided, both surgical and non-surgical treatment for ATR produce good
      functional outcome; however, the muscle function was not restored after two years
      in either group.

PMID- 11985761
TI  - Adaptation of cardiac morphology and function to endurance and strength training.
      A comparative study using MR imaging and echocardiography in males and females.
AB  - Left ventricular (LV) dimensions and function and maximal oxygen uptake
      (VO(2)max) were measured in endurance-trained (10 male, m, 10 female, f),
      strength-trained athletes (8 m, 10 f) and untrained subjects (9 m, 10 f). LV
      dimensions were measured using magnetic resonance imaging (MRI) and
      echocardiography and the results were equal irrespective of method. Endurance
      trained m and f had significantly higher LV volumes and mass than both strength
      trained and controls. No VO(2)max or dimensional differences were seen between
      strength-trained and untrained subjects. In endurance-trained males, LV volumes
      and mass/kg bw were higher than in endurance-trained females. There was no
      significant gender difference for strength-trained or untrained subjects
      regarding body weight-related heart dimensions. It is concluded that LV
      dimensions and volumes are strongly dependent on oxygen transport capacity in
      normal subjects practising different modes of training, and that the gender
      differences, if LV dimensions are related to aerobic work capacity, are smaller
      than previously reported.

PMID- 11985762
TI  - Effect of treatment with nifedipine, an L-type calcium channel blocker, on
      muscular atrophy induced by hindlimb immobilization.
AB  - The purpose of this study was to investigate whether the prevention of calcium
      influx through L-type calcium channels contributed to the attenuation of muscular
      atrophy induced by hindlimb immobilization (HI) in a shortened position. Mice
      were divided into four groups (8 mice/group): control; nifedipine; HI; and HI
      with nifedipine. Mice received nifedipine at a dose of 5 mg/kg one day before and
      during the 8 days of HI. Quantitative alterations in the amount of myosin heavy
      chain (MyHC) and actin proteins in the soleus muscle were analyzed using SDS
      PAGE. The weight of the soleus muscle decreased significantly by 40.8% (P<0.05)
      and 27.0% (P<0.05) after the hindlimb immobilization in the HI and HI with
      nifedipine groups, respectively, when compared to that of the control or
      nifedipine groups. Treatment with nifedipine alone appeared to have no effect on
      muscle mass or the amount of myofibrillar proteins. The level of MyHC proteins
      decreased significantly by 25.1% (P<0.001) and 17.4% (P<0.001) in the HI and HI
      with nifedipine groups, respectively. The level of MyHC protein in the HI with
      nifedipine group was significantly greater than that of the HI group (P<0.05),
      although there were no significant differences in the amount of actin protein.
      These findings suggest that nifedipine treatment may have a beneficial effect on
      muscular atrophy.

PMID- 11985763
TI  - Effect of salbutamol, a beta-2-adrenergic agonist, on erythropoietin
      concentration in healthy males.
AB  - Fifteen healthy males, aged 20-30 years, participated in a double-blind cross
      over study on the effect of the beta-2 stimulator salbutamol on erythropoietin
      concentration and hemoglobin concentration. The treatment period comprised
      inhalation of salbutamol, 0.8 mg four times daily for 2 weeks. Serum
      erythropoietin was essentially unaltered after treatment with salbutamol, 9.5 +/-
      4.94 IU. l-1 (mean +/- SD), as compared to both control situation, 9.2 +/- 4.50
      IU. l-1(mean +/- SD), and placebo treatment (9.7 +/- 4.07 IU. l-1) (mean+/-SD).
      The same pattern, no significant changes between control situation and treatment
      with salbutamol or placebo, also applied to hemoglobin concentration. In
      conclusion, it is not possible to increase erythropoietin concentration, and
      thereby erythropoiesis, by inhalation of high doses of the International Olympic
      Committee (IOC)-approved beta-2 stimulator salbutamol for 2 weeks in healthy
      young males.

PMID- 11985764
TI  - Skeletal muscle fatigue in long-distance runners, sprinters and untrained men
      after repeated drop jumps performed at maximal intensity.
AB  - One hundred drop jumps were performed at maximal intensity every 20 s in 12
      untrained subjects (UT), 9 sprinters (S) and 10 long-distance runners (LDR).
      Muscle contraction force (P20, P50) induced by percutaneous electrical
      stimulation (20 Hz and 50 Hz, respectively) as well as maximal voluntary
      contraction force and the height of vertical jumps performed in different ways
      decreased (P<0.05) and was not restored to the initial value 20 min post
      exercise. There was a marked increase in low frequency fatigue (LFF) in all the
      groups studied as substantiated by a significant decrease in the ratio of P20/P50
      immediately after exercise as well as 20 min post exercise compared to pre
      exercise values (P<0.05). However, low frequency fatigue was similar in UT, S and
      LDR. The jump height of the sprinters during counter-movement jump and drop jump
      at 90 degrees decreased to a smaller extent compared to jumps performed by LDR
      and UT. Muscle pain did not differ between UT, S and LDR at 24 h post exercise.
      The present data indicate that endurance training status as well as prevalence of
      muscle fibres of the slow type does not decrease muscle resistance to LFF nor
      accelerate the recovery of muscle contraction force following maximal,
      intermittent stretch-shortening cycle exercise.

PMID- 11985765
TI  - Which factors predict outcome in the treatment program of anterior knee pain?
AB  - The goal of this prospective study was to determine the outcome-predictive role
      of various parameters in the nonoperative treatment of chronic anterior knee pain
      patients. Thirty patients followed a five-week treatment program, which consisted
      out of only closed kinetic chain exercises. Prior to this treatment all subjects
      were evaluated on muscular characteristics, subjective symptoms, weight, sex,
      duration of symptoms and functional performance. A multiple stepwise regression
      analysis revealed that the reflex response time of m. vastus medialis obliquus
      (VMO) (P=0.041; 0.026), and the duration of symptoms (P=0.019; 0.045) were the
      only two parameters which were significantly associated with the outcome
      (evaluated by the Kujala score) at five weeks, and at three months. The shorter
      the duration of symptoms, or the faster the reflex response time of VMO prior to
      the treatment, the better the outcome after a closed kinetic chain exercise
      program. The statistical significance of these parameters in this study may be
      seen as an indication of the importance of these variables as predictors of the
      outcome of a closed kinetic chain strengthening program. Using this information,
      it seems clinically important to begin the treatment program before the anterior
      knee pain becomes more chronic and treatment results become less good.

PMID- 11985766
TI  - Comparison of functional outcome after anterior cruciate ligament reconstruction
      resulting in low, normal and increased laxity.
AB  - The aim of the study was to analyse and compare the results after arthroscopic
      anterior cruciate ligament (ACL) reconstruction using patellar tendon autografts
      in three groups of patients. The groups were determined by knee laxity as
      measured with the KT-1000 arthrometer at the follow-up two to five years after
      the reconstruction. Group A (n=15) had an anterior side-to-side laxity difference
      of <-3 mm (i.e. the reconstructed knee was less lax than the contralateral non
      injured knee), Group B (n=376) had a difference of > or = -1, but < or = +2 mm
      and Group C (n=38) had a difference of > or g=6 mm. All the patients had a normal
      contralateral knee. In Group A, 7/15 (47%) patients and, in Group B, 82/375 (22%)
      patients had an extension deficit of > or =5 degrees (P=0.052). The corresponding
      values in terms of flexion deficit were 8/15 (53%) and 99/375 (26%) respectively
      (P=0.04) (one missing value in Group B). In Group C, 14/38 (37%) had an extension
      deficit (P=0.04; Group B vs Group C). Group C displayed worse results than Group
      B in terms of the Lysholm score and the one-leg-hop test (P=0.001 and P=0.011
      respectively). The corresponding comparison between Group A and Group B revealed
      no significant differences. We conclude that a considerable number of patients
      showed persisting deficits in range of motion (ROM) after an ACL reconstruction.
      No major differences were found if they were analysed in subgroups with
      decreased, near normal or with increased knee laxity. The worst residual
      functional impairment, as measured with the Lysholm score and one-leg-hop test,
      was found in the group with increased knee laxity and most ROM deficits in the
      knees with decreased laxity.

PMID- 11985767
TI  - Elite athletes' experiences of the motivational climate: the coach matters.
AB  - Recent research investigating the effect of the motivational climate has found
      that even elite athletes benefit from a mastery climate. The purpose of the
      present study was to obtain a deeper understanding of the importance of the
      climate surrounding an athlete and the role of the coach for elite athletes by
      conducting in-depth interviews with a group of athletes (n=7). The athletes also
      completed the Perception of Success Questionnaire (POSQ) and Perception of
      Motivational Climate Questionnaire (PMCQ) to measure motivational indices. All
      the athletes were very high on task orientation and moderate to high on ego
      orientation. Most of the athletes perceived a high mastery climate and a low
      performance climate. The athletes emphasized the importance of the coach as the
      creator of the climate, as well as their preference for a supportive and caring
      climate. This speaks for an emphasis on a mastery climate for elite athletes.

PMID- 11985775
TI  - Weight-modification trials in older adults: what should the outcome measure be?
AB  - BACKGROUND: Overweight older adults are often counseled to lose weight, even
      though there is little evidence of excess mortality in that age group. Overweight
      and underweight may be more associated with health status than with mortality,
      but few clinical trials of any kind have been based on maximizing years of
      healthy life (YHL), as opposed to years of life (YOL). OBJECTIVE: This paper
      examines the relationship of body mass index (BMI) to both YHL and YOL. Results
      were used to determine whether clinical trials of weight-modification based on
      improving YHL would be more powerful than studies based on survival. DESIGN: We
      used data from a cohort of 4,878 non-smoking men and women aged 65-100 at
      baseline (mean age 73) and followed 7 years. We estimated mean YHL and YOL in
      four categories of BMI: underweight, normal, overweight, and obese. RESULTS:
      Subjects averaged 6.3 YOL and 4.6 YHL of a possible 7 years. Both measures were
      higher for women and whites. For men, none of the BMI groups was significantly
      different from the normal group on either YOL or YHL. For women, the obese had
      significantly lower YHL (but not YOL) than the normals, and the underweight had
      significantly lower YOL and YHL. The overweight group was not significantly
      different from the normal group on either measure. CONCLUSIONS: Clinical trials
      of weight loss interventions for obese older women would require fewer
      participants if YHL rather than YOL was the outcome measure. Interventions for
      obese men or for the merely overweight are not likely to achieve differences in
      either YOL or YHL. Evaluations of interventions for the underweight (which would
      presumably address the causes of their low weight) may be conducted efficiently
      using either outcome measure.

PMID- 11985776
TI  - Clinical significance of cardiovascular dysmetabolic syndrome.
AB  - Although diabetes mellitus is predominantly a metabolic disorder, recent data
      suggest that it is as much a vascular disorder. Cardiovascular complications are
      the leading cause of death and disability in patients with diabetes mellitus. A
      number of recent reports have emphasized that many patients already have
      atherosclerosis in progression by the time they are diagnosed with clinical
      evidence of diabetes mellitus. The increased risk of atherosclerosis and
      cardiovascular complications in diabetic patients is related to the frequently
      associated dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, and
      endothelial dysfunction. The evolving knowledge regarding the variety of
      metabolic, hormonal, and hemodynamic abnormalities in patients with diabetes
      mellitus has led to efforts designed for early identification of individuals at
      risk of subsequent disease. It has been suggested that insulin resistance, the
      key abnormality in type II diabetes, often precedes clinical features of diabetes
      by 5-6 years. Careful attention to the criteria described for the cardiovascular
      dysmetabolic syndrome should help identify those at risk at an early stage. The
      application of nonpharmacologic as well as newer emerging pharmacologic therapies
      can have beneficial effects in individuals with cardiovascular dysmetabolic
      syndrome and/or diabetes mellitus by improving insulin sensitivity and related
      abnormalities. Early identification and implementation of appropriate therapeutic
      strategies would be necessary to contain the emerging new epidemic of
      cardiovascular disease related to diabetes.

PMID- 11985777
TI  - The Myocardial Ischemia Reduction with Acute Cholesterol Lowering trial:
      MIRACuLous or not, it's time to change current practice.
AB  - The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL)
      study was the first trial to assess whether statins might be of clinical benefit
      in those with recently unstable coronary disease. MIRACL found that high-dose
      atorvastatin was safe and reduced the incidence of the composite endpoint, death,
      non-fatal myocardial infarction, resuscitated sudden cardiac death or emergent
      rehospitalization for recurrent ischemia at 16 weeks when compared with placebo.
      Despite a number of important study limitations, MIRACL's findings and the prior
      observation that inpatient initiation of lipid-lowering therapy is associated
      with higher rates of subsequent utilization, suggest that it is prudent to begin
      statin therapy when patients present with an acute coronary syndrome.

PMID- 11985778
TI  - Problems in dealing with missing data and informative censoring in clinical
      trials.
AB  - Acommon problem in clinical trials is the missing data that occurs when patients
      do not complete the study and drop out without further measurements. Missing data
      cause the usual statistical analysis of complete or all available data to be
      subject to bias. There are no universally applicable methods for handling missing
      data. We recommend the following: (1) Report reasons for dropouts and proportions
      for each treatment group; (2) Conduct sensitivity analyses to encompass different
      scenarios of assumptions and discuss consistency or discrepancy among them; (3)
      Pay attention to minimize the chance of dropouts at the design stage and during
      trial monitoring; (4) Collect post-dropout data on the primary endpoints, if at
      all possible; and (5) Consider the dropout event itself an important endpoint in
      studies with many.

PMID- 11985779
TI  - The evolutionary position of nematodes.
AB  - BACKGROUND: The complete genomes of three animals have been sequenced by global
      research efforts: a nematode worm (Caenorhabditis elegans), an insect (Drosophila
      melanogaster), and a vertebrate (Homo sapiens). Remarkably, their relationships
      have yet to be clarified. The confusion concerns the enigmatic position of
      nematodes. Traditionally, nematodes have occupied a basal position, in part
      because they lack a true body cavity. However, the leading hypothesis now joins
      nematodes with arthropods in a molting clade, Ecdysozoa, based on data from
      several genes. RESULTS: We tested the Ecdysozoa hypothesis with analyses of more
      than 100 nuclear protein alignments, under conditions that would expose biases,
      and found that it was not supported. Instead, we found significant support for
      the traditional hypothesis, Coelomata. Our result is robust to different rates of
      sequence change among genes and lineages, different numbers of taxa, and
      different species of nematodes. CONCLUSION: We conclude that insects (arthropods)
      are genetically and evolutionarily closer to humans than to nematode worms.

PMID- 11985780
TI  - Multi site polyadenylation and transcriptional response to stress of a vacuolar
      type H+-ATPase subunit A gene in Arabidopsis thaliana.
AB  - BACKGROUND: Vacuolar type H+-ATPases play a critical role in the maintenance of
      vacuolar homeostasis in plant cells. V-ATPases are also involved in plants'
      defense against environmental stress. This research examined the expression and
      regulation of the catalytic subunit of the vacuolar type H+-ATPase in Arabidopsis
      thaliana and the effect of environmental stress on multiple transcripts generated
      by this gene. RESULTS: Evidence suggests that subunit A of the vacuolar type H+
      ATPase is encoded by a single gene in Arabidopsis thaliana. Genome blot analysis
      showed no indication of a second subunit A gene being present. The single gene
      identified was shown by whole RNA blot analysis to be transcribed in all organs
      of the plant. Subunit A was shown by sequencing the 3' end of multiple cDNA
      clones to exhibit multi site polyadenylation. Four different poly (A) tail
      attachment sites were revealed. Experiments were performed to determine the
      response of transcript levels for subunit A to environmental stress. A PCR based
      strategy was devised to amplify the four different transcripts from the subunit A
      gene. CONCLUSIONS: Amplification of cDNA generated from seedlings exposed to
      cold, salt stress, and etiolation showed that transcript levels for subunit A of
      the vacuolar type H+-ATPase in Arabidopsis were responsive to stress conditions.
      Cold and salt stress resulted in a 2-4 fold increase in all four subunit A
      transcripts evaluated. Etiolation resulted in a slight increase in transcript
      levels. All four transcripts appeared to behave identically with respect to
      stress conditions tested with no significant differential regulation.

PMID- 11985781
TI  - Klippel-Feil syndrome - the risk of cervical spinal cord injury: a case report.
AB  - BACKGROUND: Klippel-Feil syndrome is defined as congenital fusion of two or more
      cervical vertebrae and is believed to result from faulty segmentation along the
      embryo's developing axis during weeks 3-8 of gestation. Persons with Klippel-Feil
      syndrome and cervical stenosis may be at increased risk for spinal cord injury
      after minor trauma as a result of hypermobility of the various cervical segments.
      Persons with Klippel-Feil Syndrome often have congenital anomalies of the urinary
      tract as well. CASE PRESENTATION: A 51-year male developed incomplete tetraplegia
      in 1997 when he slipped and fell backwards hitting his head on the floor. X-rays
      of cervical spine showed fusion at two levels: C2 and C3 vertebrae, and C4 and C5
      vertebrae. Intravenous urography (IVU) revealed no kidneys in the renal fossa on
      both sides, but the presence of crossed, fused renal ectopia in the left ilio
      lumbar region. This patient had a similar cervical spinal cord injury about 15
      years ago, when he developed transient numbness and paresis of the lower limbs
      following a fall. DISCUSSION AND CONCLUSION: 1) Persons with Klippel-Feil
      syndrome should be made aware of the increased risk of sustaining transient
      neurologic deterioration after minor trauma if there is associated radiographic
      evidence of spinal stenosis.2) Patients with Klippel-Feil syndrome often have
      congenital anomalies of the urinary tract. Our patient had crossed, fused,
      ectopia of kidney.3) When patients with Klippel-Feil syndrome sustain tetraplegia
      they have increased chances of developing urinary tract calculi. Treatment of
      kidney stones may pose a challenge because of associated renal anomalies.4)
      Health professionals caring for cervical spinal cord injury patients with Klippel
      Feil syndrome and renal anomalies should place emphasis on prevention of kidney
      stones. A large fluid intake is recommended for these patients, as a high intake
      of fluids is still the most powerful and certainly the most economical means of
      prevention of nephrolithiasis.

PMID- 11985782
TI  - A new device for measurement of fibrin clot lysis: application to the euglobulin
      clot lysis time.
AB  - BACKGROUND: Determination of clot lysis times on whole blood, diluted whole
      blood, plasma or plasma fraction has been used for many years to assess the
      overall activity of the fibrinolytic system. We designed a completely
      computerised semi-automatic 8-channel device for measurement and determination of
      fibrin clot lysis. The lysis time is evaluated by a mathematical analysis of the
      lysis curve and the results are expressed in minute (range: 5 to 9999). We have
      used this new device for Euglobulin Clot Lysis Time (ECLT) determination, which
      is the most common test used in laboratories to estimate plasma fibrinolytic
      capacity. RESULTS: The correlation between ECLT and manual method is very tight :
      R = 0,99; p < 10(-6). The efficiency scores of the method are <4% in intra-assay
      and <7% in inter-assay. It allows to achieve the tests on hyperlipaemic samples.
      This new device has been easily integrated in laboratory routine and allows to
      achieve several ECLT every day without disturbance of laboratory workflow.
      CONCLUSIONS: The routine use of this new device could be useful in various
      situations such as assessment in atherosclerosis and arteriosclerosis associated
      diseases, coagulation survey of liver transplantations, cardiovascular surgery or
      pharmacological research.It has already provided highly promising results in
      preliminary studies on the relation between fibrinolysis and cardiovascular risk
      factors.

PMID- 11985783
TI  - Lack of Ku80 alteration in multiple myeloma.
AB  - Chromosomal rearrangement involving the immunoglobulin gene locus, as a result of
      marked chromosomal instability, is the hallmark of human multiple myeloma (MM)
      cells. Since Ku80 plays a key role in the non-homologous end-joining (NHEJ)
      system, we investigated whether Ku80 alteration contributes to this genetic
      instability by examining its status in 16 MM cell lines. Our study demonstrated a
      lack of Ku80 alterations at the protein, mRNA and gene level in 15 out of the 16
      cell lines. Only the U266 cell line carried a missense mutation of Ser335Leu in
      one allele of the cDNA. Six marrow samples derived from myeloma patients also did
      not show any aberrant Ku80 protein, in terms of size. Accordingly, Ku80
      alteration is unlikely to be involved in MM, in disagreement with a previous
      study reporting frequent presence of a 69-kD Ku80 variant (Ku86v) with reduced
      DNA binding activity in MM cells.

PMID- 11985784
TI  - Autologous fixed tumor vaccine: a formulation with cytokine-microparticles for
      protective immunity against recurrence of human hepatocellular carcinoma.
AB  - We developed a tumor vaccine consisting of fixed hepatocellular carcinoma (HCC)
      cells/tissue fragments, biodegradable microparticles encapsulating granulocyte
      macrophage-colony stimulating factor and interleukin-2, and an adjuvant. The
      vaccine protected 33% of syngeneic mice from HCC cell challenge. The vaccine
      containing human autologous HCC fragments showed essentially no adverse effect in
      a phase I/IIa clinical trial and 8/12 patients developed a delayed-type
      hypersensitivity (DTH) response against the fragments. Although 2 of 4 DTH
      response-negative patients had recurrence after curative resection, the DTH
      response-positive patients had no recurrence. The time before the first
      recurrence in the vaccinated patients was significantly longer than that in 24
      historical control patients operated in the same department (P < 0.05). This
      formulation is a promising candidate to prevent recurrence of human HCC.

PMID- 11985785
TI  - Deletion of dinucleotide repeat (Delta 14 allele) in the methylthioadenosine
      phosphorylase (MTAP) promoter and the allelotype of MTAP promoter in the Japanese
      population.
AB  - 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAP) is an enzyme involved in
      purine and polyamine metabolism and is ubiquitously expressed in normal human
      tissues and cells. However, this enzyme has been found to be deficient in a
      variety of human cancers. Although the enzyme deficiency is known to be caused by
      MTAP gene deletion, human diffuse histiocytic lymphoma cell line DHL-9 without
      any detectable MTAP activity has been found to possess the intact MTAP gene.
      These lines of evidence suggested that promoter abnormality might cause the MTAP
      deficiency in DHL-9. Therefore, we analyzed the MTAP promoter region of DHL-9 and
      found the deletion of 14 bases in its sequence. We designated the allele lacking
      (GT)(6)GC as dinucleotide repeat deletion (Delta 14 allele) and determined the
      effect of the Delta 14 allele on the MTAP promoter activity by a luciferase
      reporter assay. We have also analyzed the distribution of the Delta 14 allele and
      wild-type (WT) allele in the Japanese population by PCR assay. A reporter plasmid
      harboring the Delta 14 allele exhibited luciferase activity comparable to that of
      a plasmid containing the WT allele. Forty-six (22%) out of 210 people were
      homozygous for WT allele in the MTAP promoter, whereas 43 (20.5%) were homozygous
      for Delta 14 allele. The remaining 121 people (57.5%) possessed Delta 14/WT
      alleles in the MTAP promoter region. These results indicated that the Delta 14
      allele has nothing to do with MTAP deficiency in DHL-9. The Delta 14 allele is
      distributed among the general population irrespective of gender.

PMID- 11985786
TI  - Reversibility of heterotopic proliferative glands in glandular stomach of
      Helicobacter pylori-infected Mongolian gerbils on eradication.
AB  - Helicobacter pylori (Hp) infection is an important factor in human gastric
      disorders. Mongolian gerbils can be easily infected with Hp and represent
      excellent experimental models to clarify the role of Hp in chronic active
      gastritis, peptic ulcers, intestinal metaplasia, and gastric carcinoma. We have
      proved the enhancing effects of Hp infection on all histological types of gastric
      cancers in Mongolian gerbils exposed to chemical carcinogens. Heterotopic
      proliferative glands (HPGs) also frequently develop with Hp infection in the
      glandular stomach of infected gerbils, with a slightly dysplastic change of
      constituent cells. Distinguishing reversible inflammatory lesions from true
      neoplasms upon eradication is necessary for further biological or histochemical
      investigations using this model. We employed an experimental model of long-term
      Hp infection and eradication in gerbils. HPGs finally developed with a phenotypic
      shift of intestinalization with Paneth cells. After eradication, HPGs were
      obviously reduced, and gastric lesions in mucosa also improved with few remnants
      of the former injury. This shows that reversible HPGs are frequently induced
      solely by Hp infection in this animal species, and are related to severe
      gastritis, rather than being malignant in character. Thus, distinguishing
      reversible lesions from true neoplasms is necessary to investigate the
      relationship of Hp infection and gastric carcinogenesis in this animal model.

PMID- 11985787
TI  - Frequent and multiple mutations at minisatellite loci in sporadic human
      colorectal and gastric cancers--possible mechanistic differences from
      microsatellite instability in cancer cells.
AB  - Minisatellites (MNs), composed of 5 to 100 nucleotide repeat units, range from
      0.5 to 30 kb in length, and have been reported to be mutated in various human
      malignancies. In this study, frequencies of MN mutations in sporadic human
      colorectal (34 cases) and gastric cancers (24 cases) at various
      clinicopathological stages were assessed by multilocus DNA fingerprint analysis
      with three MN probes, Pc-1, 33.6 and 33.15. MN mutations were observed in both
      colorectal and gastric cancers, but at a significantly higher frequency in the
      former (56%) than in the latter (25%). Multiplicities of MN mutations were 1.50
      +/- 1.81 and 0.46 +/- 1.10 in colorectal and gastric cancers, respectively, and
      the difference was also significant. Neither the presence nor multiplicity of MN
      mutations in either colorectal or gastric cancer cases had any correlation with
      the pathological stage, histological grading or the presence of microsatellite
      instability (MSI). Although the biological relevance of MN mutations still
      remains to be clarified, a subset of colorectal and gastric cancers could feature
      a new type of genomic instability, distinct from MSI.

PMID- 11985788
TI  - Expression of macrophage migration inhibitory factor in human breast cancer:
      association with nodal spread.
AB  - Macrophage migration inhibitory factor (MIF) is known to exert pleiotropic
      functions including inhibition of macrophage migration, anchoring, and
      counteraction of the anti-inflammatory and immunosuppressive activity of
      glucocorticoids. Ninety-three primary breast cancer tissues and 64 sera of
      primary breast cancer patients were analyzed for the expression of MIF. The
      clinico-pathological significance of MIF expression was evaluated. It was found
      that MIF was frequently over-expressed in primary breast cancer tissues. RT-PCR
      and western blotting analysis confirmed that wild-type MIF is expressed, and
      immunohistochemical analysis showed that MIF expression was localized at tumor
      cells as well as stromal cells, including tumor-associated macrophages.
      Intratumoral MIF protein concentrations detected by enzyme-linked immunosorbent
      assay (ELISA) varied with a median value of 1821 ng/mg protein (range: 8 - 8126
      ng/mg protein), and correlated inversely with nodal involvement (P = 0.039). No
      significant correlation was observed with other clinico-pathological factors
      including tumor size, menopausal status and hormone receptors. The circulating
      level of MIF protein ranged up to 105.7 ng/ml (median: 17.3 ng/ml), and it was
      also found to correlate inversely with the number of involved nodes (P = 0.02). A
      comparative study with other soluble inflammatory mediators showed that
      intratumoral levels of MIF were significantly associated with those of
      interleukin-1 beta, suggesting that interactions between tumor cells and tumor
      associated macrophages play an important role in the up-regulation of MIF. The
      multifunctional inflammatory/immune mediator MIF was frequently expressed in
      primary breast cancer, and its expression level was inversely associated with
      nodal spread. Thus, MIF seems to play a role in tumor-stroma interactions of
      primary breast cancers, particularly those with a phenotype of node-negative or
      minimal nodal spread.

PMID- 11985789
TI  - Expansion of lung V alpha 14 NKT cells by administration of alpha
      galactosylceramide-pulsed dendritic cells.
AB  - NKT cells, a novel murine lymphoid lineage bearing an invariant T cell receptor
      encoded by V alpha 14 and J alpha 281 gene segments, recognize a specific ligand
      glycolipid, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner.
      Recent research has revealed that activated V alpha 14 NKT cells have dramatic
      antitumor effects against a wide variety of tumor cell lines in vivo and in
      vitro. Here, we demonstrate strong in vivo antitumor effects brought about by
      treatment with alpha-GalCer-pulsed dendritic cells in comparison with in vitro
      activated V alpha 14 NKT cells. Furthermore, we show a significant expansion of
      endogenous V alpha 14 NKT cells in the lung following the administration of alpha
      GalCer-pulsed dendritic cells. The feasibility of immunotherapy with alpha-GalCer
      pulsed dendritic cells is discussed.

PMID- 11985790
TI  - Association of HLA-DQB1*0301 and HLA-DQB1*0602 with different subtypes of gastric
      cancer in Taiwan.
AB  - Gastric cancer (GC) is a heterogeneous disorder with multifactorial etiologies.
      Genetic predisposition, environmental factors, and Helicobacter pylori infection
      are thought to interact in the manifestation of GC. Particular human leukocyte
      antigen (HLA) alleles play a pivotal role in cellular immunity and may be an
      important genetically determined host trait. To elucidate the association between
      the genotype of HLA class II genes and the clinical phenotype of GC,
      polymorphisms of HLA-DRB1 and HLA-DQB1 were determined by polymerase chain
      reaction with sequence-specific primers in 106 Taiwanese patients with GC and in
      208 healthy controls. Comparison of allele frequencies between GC patients and
      healthy controls showed no significant difference at the HLA-DRB1 locus. Patients
      with GC had a higher frequency of DQB1(*)0602 (9.4% vs. 3.6%, P < 0.05, odds
      ratio 2.79, 95% confidence interval 1.41 - 5.47) and a lower frequency of
      DQB1(*)0301 (14.6% vs. 23.8%, P < 0.05, odds ratio 0.55, 95% confidence interval
      0.35 - 0.85) compared to healthy controls. Correlation of HLA-DQB1 status with
      clinicopathologic features revealed predominance of male gender (16/3 vs. 50/37,
      P < 0.05) and proximal location (12/7 vs. 28/59, P < 0.05) in patients with
      positive HLA-DBQ1(*)0602 compared to those with negative HLA-DBQ1(*)0602. In
      contrast, a higher ratio of diffuse/intestinal subtype (20/10 vs. 30/46, P <
      0.05) and a lower seropositivity of Helicobacter pylori (14/30 vs. 58/76, P <
      0.005) were noted in patients with positive HLA-DQB1(*)0301 compared to those
      with negative HLA-DQB1(*)0301. In conclusion, HLA-DQB1(*)0602 confers
      susceptibility to gastric cancer, especially for male Taiwanese and proximal
      tumor location, while HLA-DQB1(*)0301 may have a protective effect on GC,
      probably through resistance to Helicobacter pylori infection. HLA-DQB1 alleles
      are associated with susceptibility or resistance to GC and also influence its
      clinical features.

PMID- 11985791
TI  - Enhanced expression of neuron-specific enolase (NSE) in pyothorax-associated
      lymphoma (PAL).
AB  - Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma of mostly large cell
      type developing in the pleural cavity of patients with long-standing pyothorax.
      Neuron-specific enolase (NSE) is an enolase comprising gamma subunit and is
      located at high levels in neuronal and neuroendocrine cells, together with their
      neoplasias. Expression of NSE at protein and mRNA levels was examined in PAL and
      other types (non-PAL) of non-Hodgkin's lymphomas. In PAL, serum levels of NSE
      were elevated (5.32 to 168.0, mean 42.6 ng/ml) and tended to decrease after
      incisional biopsy followed by chemotherapy (2.38 to 195.5, mean 34.1 ng/ml). Two
      cell lines established from two cases of PAL produced and secreted NSE in the
      culture medium. Immunohistochemistry revealed that the positive rate for NSE
      staining in PAL (10 of 14 cases, 71.4%) was significantly higher than that in non
      PAL cases (6 of 38 cases, 15.8%) (P < 0.01). RT-PCR analysis showed that the
      expression levels of NSE mRNA in two cell lines and a biopsy sample from PAL were
      rather similar to those of the control samples from non-neoplastic lymph nodes.
      These findings suggest the posttranscriptional regulation of NSE in PAL. Thus, an
      elevation of serum NSE level in patients with chronic pyothorax may be an
      indicator of PAL development.

PMID- 11985792
TI  - Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the
      modulation of mitochondrial function in endothelial cells.
AB  - Betulinic acid (BetA), a pentacyclic triterpene, is a selective apoptosis
      inducing agent that works directly in mitochondria. Recent study has revealed
      that BetA inhibits in vitro enzymatic activity of aminopeptidase N (APN, EC
      3.4.11.2), which is known to play an important role in angiogenesis, but the anti
      angiogenic activity of BetA has not been reported yet. Data presented here show
      that BetA potently inhibited basic fibroblast growth factor (bFGF)-induced
      invasion and tube formation of bovine aortic endothelial cells (BAECs) at a
      concentration which had no effect on the cell viability. To access whether the
      anti-angiogenic nature of BetA originates from its inhibitory action against
      aminopeptidase N (APN) activity, the effect of BetA on APN was investigated.
      Surprisingly, BetA did not inhibit in vivo APN activity in endothelial cells or
      APN-positive tumor cells. On the other hand, BetA significantly decreased the
      mitochondrial reducing potential, and treatment with mitochondrial permeability
      transition (MPT) inhibitors attenuated BetA-induced inhibition of endothelial
      cell invasion. These results imply that anti-angiogenic activity of BetA occurs
      through a modulation of mitochondrial function rather than APN activity in
      endothelial cells.

PMID- 11985793
TI  - Macrophage colony-stimulating factor (M-CSF) prevents infectious death induced by
      chemotherapy in mice, while granulocyte-CSF does not.
AB  - To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and
      macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced
      infection, we estimated the effect of those CSFs on a mouse model under severe
      myelosuppression. First, we established an animal model in which 48.9% (22/45) of
      C3H/Hej mice died of sepsis related to severe myelosuppression after
      intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G
      CSF or M-CSF was administered to this model on various administration schedules
      after chemotherapy, and the effect of those CSFs on survival rates, peripheral
      blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18)
      on granulocytes and granulocyte function (phagocytosis and superoxide anion
      production) were examined. In all G-CSF administration groups, peripheral blood
      granulocyte counts were increased, but improvements in expression of adhesion
      molecules such as CD11a and CD18, and granulocyte function were less marked and
      survival rates were not improved. Meanwhile, when M-CSF was administered from 1
      to 7 days after chemotherapy, granulocyte and platelet counts were increased, and
      moreover, expression of adhesion molecules and granulocyte function were markedly
      improved. Furthermore, the survival rate was significantly improved to 77.8%
      (28/36) compared with the MMC group (P < 0.05). Positive rate of blood culture
      examination at 7 days after chemotherapy in the M group was 0%, and was
      significantly lower than that in the G group (40%) and the MMC group (40%) (P <
      0.05). These results demonstrated that it is important not only to increase the
      granulocyte counts, but also to improve granulocyte functions for preventing
      infection under myelosuppression after chemotherapy.

PMID- 11985794
TI  - Tumor necrosis factor alpha-gene therapy for an established murine melanoma using
      RGD (Arg-Gly-Asp) fiber-mutant adenovirus vectors.
AB  - Although adenovirus vectors (Ad) provide high-level transduction efficacy to many
      cell types, extremely high doses of Ad are required for sufficient gene
      transduction into several tumors, including melanoma. Here, we demonstrated that
      the expression of coxsackie-adenovirus receptor, a primitive Ad-receptor, was
      very low in murine and human melanoma cells. We also found that fiber-mutant Ad
      containing the Arg-Gly-Asp (RGD) sequence in the fiber knob remarkably augmented
      gene transduction efficacy in melanoma cells by targeting alpha(v)-integrins. In
      addition, intratumoral injection of RGD fiber-mutant Ad containing the tumor
      necrosis factor alpha gene (Ad-RGD-TNFalpha) revealed dramatic anti-tumor
      efficacy through hemolytic necrosis in an established murine B16 BL6 melanoma
      model. Ad-RGD-TNFalpha required one-tenth the dosage of Ad-TNFalpha to induce an
      equal therapeutic effect. These results suggest that alpha(v)-integrin-targeted
      Ad will be a very powerful tool for the advancement of melanoma gene therapy.

PMID- 11985795
TI  - Cellular and biochemical mechanisms of the resistance of human cancer cells to a
      new anticancer ribo-nucleoside, TAS-106.
AB  - We have established variants of DLD-1 human colon carcinoma and HT-1080 human
      fibrosarcoma cells resistant to the new anticancer ribo-nucleosides, 1-(3-C
      ethynyl-beta-D-ribo-pentofuranosyl)-cytosine (ECyd, TAS-106) and 1-(3-C-ethynyl
      beta-D-ribo-pentofuranosyl)uracil (EUrd). Both variants were shown to have
      decreased (3- to 24-fold decrease) uridine-cytidine kinase (UCK) activity, and
      exhibited cross-resistance to EUrd and TAS-106. Based on the IC(50) values
      determined by chemosensitivity testing, a 41- to 1102-fold resistance to TAS-106
      was observed in the resistant cells. TAS-106 concentration-dependently inhibited
      RNA synthesis, while its effect on DNA synthesis was negligible. The degree of
      resistance (14- to 3628-fold resistance) calculated from the inhibition of RNA
      synthesis tended to be close to the degree of chemoresistance of tested cells to
      TAS-106. The experiments on the intracellular metabolism of TAS-106 in the
      parental cells revealed a rapid phosphorylation to its nucleotides, particularly
      the triphosphate (ECTP), its major active metabolite. The amount of TAS-106
      transported into the resistant cells was markedly reduced and the intracellular
      level of ECTP was decreased from 1/19 to below the limit of detection; however,
      the unmetabolized TAS-106 as a percentage of the total metabolite level was high
      as compared with the parental cells. The ratio of the intracellular level of ECTP
      between parental and resistant cells tended to approximate to the degree of
      resistance calculated from the inhibitory effect on RNA synthesis. These results
      indicate that the TAS-106 sensitivity of cells is correlated with the
      intracellular accumulation of ECTP, which may be affected by both the cellular
      membrane transport mechanism and UCK activity.

PMID- 11985796
TI  - Elevation of serum MAGE-4 protein levels and prediction of hepatocellular
      carcinogenesis in patients with liver cirrhosis.
AB  - Early detection of hepatocellular carcinoma (HCC) is clinically important because
      advanced HCC limits treatment modalities for the cancer. We have previously
      reported that serum levels of MAGE-4 protein are strongly associated with the
      development of HCC. The present study was designed to determine whether elevated
      serum MAGE-4 protein levels can predict hepatocellular carcinogenesis in patients
      with liver cirrhosis before clinical diagnosis. Among 62 cirrhotic patients, 28
      patients were diagnosed with HCC during the follow-up period. The levels of MAGE
      4 protein and alpha-fetoprotein (AFP) were significantly elevated in cirrhotic
      patients with HCC. Univariate and multivariate analyses suggest that elevated
      serum MAGE-4 protein is more significant than AFP. Importantly, retrospective
      analysis of prefrozen sera of cirrhotic patients revealed a transient or
      continuous elevation of serum MAGE-4 protein levels in 14 of 28 cirrhotic
      patients with HCC (50%) before clinical diagnosis. In contrast, elevated serum
      MAGE-4 protein levels were observed in 3 of 33 cirrhotic patients without HCC
      (9%), and in 2 of 34 hepatitic patients (6%). These results indicate that
      elevated serum MAGE-4 protein levels can be a predictive marker of hepatocellular
      carcinogenesis in cirrhotic patients, thereby enabling us to treat patients at an
      earlier stage.

PMID- 11985797
TI  - Elevated level of plasma basic fibroblast growth factor in multiple myeloma
      correlates with increased disease activity.
AB  - Recent reports that bone marrow angiogenesis is increased in multiple myeloma
      prompted us to examine plasma concentrations of angiogenic growth factors and to
      elucidate their clinical and biological significance. In 45 cases including 36
      cases of multiple myeloma and 9 cases of monoclonal gammopathies of undetermined
      significance (MGUS), plasma concentrations of basic fibroblast growth factor (FGF
      2) and vascular endothelial growth factor (VEGF) were evaluated. FGF-2 was
      significantly elevated in 25 out of 45 (56%) of the patients with multiple
      myeloma compared with control subjects (median 9.01 pg ml vs. 1.58 pg/ml, P <
      0.0001). The 25 cases were all active multiple myeloma, and none of the non
      active myeloma and MGUS patients showed a high FGF-2 level. VEGF level was also
      elevated in 26 out of 45 patients (58%) compared with control subjects (median
      42.0 pg/ml vs. 15.8 pg/ml, P < 0.0001 for VEGF). VEGF concentration was high in
      20 active myelomas, but also in one non-active myeloma and five MGUS. Elevation
      of FGF-2 level was associated with beta2-microglobulin level, anemia and bone
      marrow plasma cell percentage, which represent disease activity. Interestingly,
      none of five Bence-Jones type myelomas, including four clinically active cases,
      revealed a high plasma FGF-2 level, while all of them showed a high VEGF level.
      In all five responders, the plasma FGF-2 levels were significantly decreased
      after chemotherapy. FGF-2 was immunohistochemically detected in the bone marrow
      myeloma cells of the patients with high plasma FGF-2 level. We conclude that
      plasma concentration of FGF-2 can be a useful indicator of disease activity.

PMID- 11985798
TI  - [Study of hepatitis B virus replication and infection by other hepatitis viruses
      in patients with chronic hepatitis B virus infection].
AB  - AIM: To study hepatitis B virus (HBV) replication in a series of patients with
      HBV infection and to analyze the frequency of associated hepatitis C virus (HCV)
      and hepatitis D (HDV) infection. PATIENTS AND METHOD: Serological markers of HBV,
      HCV and HDV, transaminase values and HBV DNA were studied in serum samples from
      463 patients with chronic HBV infection. RESULTS: Three hundred ninety-six
      (85.5%) were classified as hepatitis B, 33 (7.1%) as hepatitis B and C, 17 (3.6%)
      as hepatitis B and D and 17 (3.6%) as hepatitis B, C and D. Sixty-seven percent
      of patients with hepatitis B and 33% of those with chronic hepatitis B were
      asymptomatic HBsAg carriers. HVB DNA was identified in 27.7% of patients with
      hepatitis B, in 24% of those with hepatitis B and C, in 11.7% of those with
      hepatitis B and D and in 29.4% of those with hepatitis B, C and D. HBV DNA and
      elevated transaminase levels were found in 63% of HBeAg-positive patients and in
      only 16% of those who were anti-HBe-positive. These latter were considered
      candidates for antiviral treatment. CONCLUSIONS: In our environment, most
      patients with HBV infection are asymptomatic HBsAg carriers. Viral replication
      and elevated alanine aminotransferase levels were found in 22% of the patients.
      Consequently, these patients are candidates for antiviral treatment. Between 3.6%
      and 7.1% of patients with hepatitis B presented coinfection with HCV or HDV, or
      both. No significant differences were found in HBV replication among the
      different groups.

PMID- 11985799
TI  - [Effect of exogenous administration of platelet-derived growth factor and
      epidermal growth factor on duodenal ulcer healing in rats treated with
      indomethacin].
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) delay peptic ulcer
      healing through mechanisms that are still not entirely understood. Growth factors
      play a significant role in healing. AIM: To evaluate whether exogenous
      administration of platelet-derived growth factor (PDGF) reverses the effect of
      indomethacin in experimental duodenal ulcers in rats and to define the potential
      mechanisms involved in this process. METHOD: Duodenal ulcer was induced in male
      Wistar rats with acetic acid. The rats were then administered indomethacin (2
      mg/kg/day), PDGF-BB (30 ng/100 g/day), epidermal growth factor (EGF) (50 /kg/day)
      or famotidine (positive control) or the possible combinations of these.
      Macroscopic area, reduction in microscopic diameter, epithelial and granulation
      tissue proliferation, collagen secretion by granulation tissue, and gastric acid
      secretion were analyzed. RESULTS: Indomethacin delayed duodenal ulcer healing by
      decreasing cellular proliferation and inhibiting collagen secretion. PDGF and EGF
      accelerated healing and reversed the effects of indomethacin. The mechanisms
      involved were associated with an increase in collagen proliferation and secretion
      without affecting gastric acid secretion. Famotidine also accelerated healing and
      reversed the effect of indomethacin, and these effects were associated with a
      marked inhibition of gastric acid secretion and increase in collagen secretion by
      granulation tissue. CONCLUSIONS: Exogenous administration of PDGF and EGF
      accelerated healing and reversed the harmful effects of indomethacin in an
      experimental model of duodenal ulcer.

PMID- 11985800
TI  - [Frequent Internet use among Catalan patients with inflammatory bowel disease].
AB  - No data are available on the use of the Internet by Spanish patients with chronic
      diseases. AIM: To determine the extent to which patients with inflammatory bowel
      disease (IBD) in Barcelona (Spain) make use of the Internet and the relationship
      between Internet use and demographic characteristics. METHOD: A questionnaire on
      Internet use was administered to 200 patients attending an information session on
      IBD organized by the Gastroenterology Department of a university referral
      hospital in the city of Barcelona. RESULTS: Replies were received from 86% of
      those surveyed. The mean age was 40 years and 60% were women. Sixty-eight percent
      had home computers and 49% had an Internet connection. Forty-four percent
      sporadically or regularly obtained information on IBD from the web. A positive
      correlation was found between availability and Internet use and young age and
      higher educational level. No differences were found between men and women. Eighty
      four percent expressed interest in having a web site on IBD supported by the
      physicians of their referral center and 65% were prepared to pay a subscription
      for this service. CONCLUSION: Patients with IBD from Barcelona frequently looked
      for information on their disease on the Internet and were receptive to
      initiatives concerning electronic information from physicians of their local
      referral center.

PMID- 11985801
TI  - [Constipation and digestive bleeding as an atypical presentation of Whipple's
      disease].
AB  - Whipple's disease is a rare systemic disease of infectious etiology. Its clinical
      presentation is highly variable. The most common symptoms are diarrhea, weight
      loss, abdominal pain and joint manifestations. Non-digestive manifestations
      frequently precede digestive symptoms by several years. For all these reasons,
      diagnosis is difficult. Definitive diagnosis is established by the finding of PAS
      positive macrophages in the lamina propria of the thin intestine. It is important
      to start appropriate antibiotic therapy early, as this improves the prognosis. We
      present the case of a male patient in whom the first manifestations of the
      disease were constipation and upper gastrointestinal hemorrhage, two forms of
      clinical presentation that have rarely been described in the literature on
      Whipple's disease.

PMID- 11985803
TI  - [Anal neosphincters in the treatment of fecal incontinence].

PMID- 11985802
TI  - [Idiopathic cholestasis associated with progressive ductopenia in two patients
      with hodgkin's disease].
AB  - INTRODUCTION: Jaundice in Hodgkin's disease can be due to several causes. Ductal
      lesions and ductopenia, which we describe below, have rarely been reported. CASE
      REPORT: We describe 2 cases of idiopathic cholestasis associated with Hodgkin's
      disease in which duction lesions and ductopenia were found. In one case, the
      ductal lesion progressed to ductopenia and the patient died from complications of
      her oncological disease while in the second case, outcome was favorable with
      improvement of cholestasis and remission of Hodgkin's lymphoma. DISCUSSION:
      Ductopenia should be included in the differential diagnosis of cholestasis
      associated with Hodgkin's disease, for which a high degree of suspicion is
      required. Hodgkin's disease should be suspected when ductopenia is found.

PMID- 11985804
TI  - [Indications for azathioprine treatment in inflammatory bowel disease].

PMID- 11985805
TI  - [Hepatotoxicity due to herbal infusion].

PMID- 11985806
TI  - [ERCP in the diagnosis of delayed rupture of the gallbladder].

PMID- 11985807
TI  - [Adenosquamous carcinoma of the gallbladder. What are the prognostic implications
      of this histological variant?].

PMID- 11985808
TI  - [Viral genotypes in patients with hepatitis C virus infection in Medellin].

PMID- 11985809
TI  - [Treatment of postoperative intrahepatic biloma due to liver trauma with external
      percutaneous drainage].

PMID- 11985810
TI  - [Immunohemolytic anemia associated with acute hepatitis B virus infection].

PMID- 11985811
TI  - [Treatment of chronic hepatitis C in patients with HIV-coinfection].

PMID- 11985812
TI  - [Antiviral treatment of chronic hepatitis C in interferon nonresponders].

PMID- 11985813
TI  - [Chronic hepatitis C: initial treatment in patients without previous treatment].

PMID- 11985814
TI  - [Treatment of chronic hepatitis C in cirrhosis of the liver].

PMID- 11985815
TI  - G-protein-coupled receptors, tyrosine kinases and neurotransmission.

PMID- 11985816
TI  - Calcineurin acts via the C-terminus of NR2A to modulate desensitization of NMDA
      receptors.
AB  - Phosphatase IIb (calcineurin, CaN) can reduce N-methyl-D-aspartate (NMDA)
      synaptic responses by enhancing glycine-independent desensitization. We examined
      the action of CaN on desensitization in recombinant NMDA receptors comprised of
      NMDA receptor 1 (NR1) and NR2A subunits. The C-terminus of NR2A, but not NR1, was
      critical for modulation of desensitization by CaN. Alanine-scanning mutagenesis
      indicated that serines 900 and 929 in NR2A altered desensitization, as did
      inhibition of tyrosine phosphatases. Our data suggest that dephosphorylation
      dependent regulation of the C-terminus of NR2A increases desensitization of NMDA
      receptors, providing an additional mechanism for modulation of synaptic signals.

PMID- 11985817
TI  - Functional characterization of kainate receptors in the mouse nucleus accumbens.
AB  - Kainate receptors are abundantly expressed in the nucleus accumbens but their
      functional characterization and their role in synaptic transmission has not yet
      been investigated. Using patch-clamp recordings in mouse nucleus accumbens
      slices, we show the presence of functional kainate receptors activated by low
      concentrations of kainate (100-300 nM) in medium size neurons. These
      somatodendritic receptors are comprised of the GluR6 subunit, since they are
      absent in GluR6-deficient mice. Kainate receptors do not directly participate in
      glutamatergic synaptic transmission evoked by electrical stimulation of cortical
      afferent fibers in nucleus accumbens neurons. However, application of low
      concentrations of kainate inhibits cortico-accumbens synaptic transmission, by
      increasing synaptic failure rate and increasing variation coefficient, thus
      indicating a presynaptic site of action. Presynaptic kainate receptors are
      observed both in GluR6 and in GluR5-deficient mice, but are absent in mice devoid
      of both subunits. Hence, at variance with somatodendritic kainate receptors,
      presynaptic kainate receptors on cortical afferents are composed of both GluR5
      and GluR6 kainate receptor subunits. These results indicate that different
      subtypes of kainate receptors, representing distinct pharmacological targets,
      should play important roles in the synaptic integration properties of nucleus
      accumbens neurons.

PMID- 11985818
TI  - Protection of methylmercury effects on the in vivo dopamine release by NMDA
      receptor antagonists and nitric oxide synthase inhibitors.
AB  - The possible protective effects of NMDA receptor antagonists dizocilpine (MK-801)
      and D(-)-2-amino-5-phosphonopentanoic acid (AP5), and nitric oxide synthase (NOS)
      inhibitors L-nitro-arginine methyl ester (L-NAME) and 7-nitro-indazol (7-NI) on
      the methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were
      investigated using in vivo microdialysis. Intrastriatal infusion of 400 microM or
      4 mM MeHg increased the extracellular DA levels to 1941+/-199 and 7971+/-534%
      with respect to basal levels. Infusion of 400 microM or 4 mM MeHg in 400 microM
      MK-801 pretreated animals, increased striatal DA levels to 677+/-126 and 2926+/
      254%, with respect to basal levels, these increases being 65 and 63% smaller than
      those induced by MeHg in non-pretreated animals. Infusion of 400 microM or 4 mM
      MeHg in 400 microM AP5 pretreated animals, increased striatal DA levels to 950+/
      234 and 2251+/-254% with respect to basal levels, these increases being 51 and
      72% smaller than those induced by MeHg in non-pretreated animals. Infusion of 400
      microM MeHg in 100 microM L-NAME or 7-NI pretreated animals, increased the
      extracellular DA levels to 1159+/-90 and 981+/-292%, with respect to basal
      levels, these increases being 40 and 50% smaller than those induced by MeHg in
      non-pretreated animals. In summary, MeHg acts, at last in part, through an
      overstimulation of NMDA receptors with possible NO production to induce DA
      release, and administration of NMDA receptor antagonists and NOS inhibitors
      protects against MeHg-induced DA release from rat striatum.

PMID- 11985819
TI  - Tolerance to the sedative effect of lorazepam correlates with a diminution in
      cortical release and affinity for glutamate.
AB  - Benzodiazepines are anxiolytic, anticonvulsant, sedative and hypnotic compounds
      usually prescribed on a long-term basis. Chronic treatment with these compounds
      induces tolerance, which has been extensively attributed to modifications in the
      GABAergic neurotransmission. However, a compensatory increase in the excitatory
      response, named as an oppositional response, has also been put forward as a means
      for explaining such tolerance. Changes in the excitatory neurotransmission have
      been found in withdrawn rats after a long treatment with benzodiazepines but
      these modifications have not been conclusively studied during tolerance. In this
      work we studied several parameters of the glutamatergic neurotransmission in rats
      made tolerant to the sedative effect of 3 mg/kg (i.p.) of lorazepam (LZ). We
      found a decrease in the affinity of cortical NMDA receptors for (3)H-glutamate
      (K(D): 124.4 +/- 13.3 nM in tolerant rats, 71.6 +/- 10.4 nM in controls, P<0.05)
      together with a decrease in the in vitro 60 mM K(+)-stimulated cortical glutamate
      release (59+/- 12% vs. 153 +/- 38%, tolerant rats vs. controls, P<0.05). We
      conclude that tolerance to the sedative effect of LZ correlates with a decreased
      sensitivity for glutamate that may in turn diminish the cortical response to a
      chemical stimulus. Our findings constitute an evidence against the oppositional
      model of pharmacodynamic tolerance in this experimental condition.

PMID- 11985820
TI  - CGP 44532, a GABAB receptor agonist, is hedonically neutral and reduces cocaine
      induced enhancement of reward.
AB  - Drugs that alter the function of gamma-aminobutyric acid (GABA) neurotransmission
      seem to reduce cocaine reinforcement, and as such may be useful in
      pharmacologically treating cocaine addiction. In the present experiment, the anti
      cocaine effects of CGP 44532, a phosphinic acid analogue of GABA, and a highly
      selective GABA(B) receptor agonist were examined in male Sprague-Dawley rats
      using brain stimulation reward (BSR) paradigm. In this method, the relationship
      between the rate of bar pressing and the frequency of stimulation pulses was
      analyzed in two measures: the maximum rate of responding (MAX) and the frequency
      necessary to sustain half maximal rate of responding known as the locus of rise
      (LOR). CGP 44532 was found to be hedonically neutral without producing any
      measurable effects on performance (MAX). It also dose-dependently reduced cocaine
      induced BSR enhancement, in the order of 15-31%, as shown by progressive shifts
      in LOR towards baseline. Thus, in theory, administration of CGP 44532 might
      reduce cocaine's hedonic effects, while also maintaining patient compliance.
      Whether this agent would also be effective at curbing craving, a long-term
      consequence of drug abuse, remains to be determined.

PMID- 11985821
TI  - Increased conditioned fear response and altered balance of dopamine in the shell
      and core of the nucleus accumbens during amphetamine withdrawal.
AB  - It has been suggested that neuroadaptations within the nucleus accumbens (NAC)
      dopaminergic (DA) projection contribute to the negative affect associated with
      psychostimulant withdrawal. The present study assessed the effects of amphetamine
      (AMPH) withdrawal on behavioral and NAC DA responses to conditioned fear stress.
      Animals injected with escalating-dose AMPH (1-5mg/kg, three injections/day, 6
      days) or saline (SAL) acquired a tone-shock association on withdrawal day 3 and
      were tested for extinction of conditioned freezing to the tone on withdrawal day
      4. Extracellular levels of NAC shell and core DA were monitored using in vivo
      microdialysis on both days. AMPH-withdrawn animals exhibited more conditioned
      freezing than SAL animals during both acquisition and extinction. During
      acquisition, DA increased more in the shell than the core of the NAC in both AMPH
      and SAL groups. During extinction to the tone, shell DA increased in SAL- but not
      AMPH-treated animals, whereas core DA activity was greater in AMPH than SAL
      animals. These data demonstrate that AMPH withdrawal alters the balance between
      shell and core DA transmission while increasing the behavioral expression of
      conditioned fear. Such drug-induced neuroadaptations in the NAC stress response
      may be involved in the exacerbation of negative emotions associated with drug
      withdrawal and stimulant-induced psychosis.

PMID- 11985822
TI  - Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial
      movement topographies in congenic dopamine D1A receptor 'knockout' mice.
AB  - A novel system was used to assess the role of D(1)-like dopamine receptors in
      distinct topographies of orofacial movements in mice with congenic D(1A) receptor
      knockout. Under spontaneous conditions, vertical jaw movements in wild-types
      declined with time at a rate that was reduced in D(1A) mutants, while horizontal
      jaw movements emerged progressively in wild-types but not in D(1A) mutants;
      tongue protrusions were absent in D(1A) mutants, while incisor chattering was
      initially reduced in D(1A) mutants but rose subsequently to reach the level of
      wild-types. D(1A) receptors exert a topographically specific role in regulating
      individual spontaneous orofacial movements, and these involve interactions with
      psychomotor processes which 'sculpt' behavioural change over time. The anomalous
      D(1)-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the
      stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical
      jaw movements, tongue protrusions and incisor chattering, and these response
      topographies were absent in D(1A) mutants. These results suggest that D(1A)
      receptors may exert some form of permissive role over orofacial topographies
      initiated via a novel, putative D(1)-like site not linked to adenylyl cyclase, or
      that some D(1A) receptors might be coupled to a transduction system other than
      adenylyl cyclase.

PMID- 11985823
TI  - Nicotinic acetylcholine receptor-mediated release of [3H]norepinephrine from
      developing and adult rat hippocampus: direct and indirect mechanisms.
AB  - The primary role of nicotinic acetylcholine receptors in adult and developing
      brain is to modulate neurotransmission. Using in vitro neurotransmitter release,
      we have examined mechanisms underlying nicotine-induced [(3)H]norepinephrine
      release from developing and adult rat hippocampus. At birth, nicotine
      significantly stimulated hippocampal [(3)H]norepinephrine release with a
      monotonic increase in maximal drug effect over the first ten postnatal days. No
      developmental changes in agonist or antagonist potency were observed. Comparison
      of synaptosomal and slice preparations, as well as examination of the effects of
      tetrodotoxin, indicated that at least two nicotinic acetylcholine receptor
      populations regulated [(3)H]norepinephrine release from neonatal and adult
      hippocampus; one localized on noradrenergic terminals, the other on adjacent
      cells. To further characterize the indirect mechanism of nicotine action in the
      adult, we examined the effects of pharmacological blockade of various
      neurotransmitter systems that provide excitatory input to hippocampal
      noradrenergic terminals. Whereas glutamate and muscarinic receptor blockade was
      ineffective, the GABA-A receptor antagonists, bicuculline and picrotoxin,
      inhibited the indirect component of nicotine-mediated [(3)H]norepinephrine
      release. Furthermore, pentobarbital, an allosteric effector at GABA-A receptors,
      potentiated the effect of submaximal concentrations of nicotine. These findings
      are consistent with the hypothesis that nicotine-induced GABA release serves as
      an additional stimulus for [(3)H]norepinephrine secretion within rat hippocampus.

PMID- 11985824
TI  - Inhibition of skeletal muscle nicotinic receptors by the atypical antipsychotic
      clozapine.
AB  - We have previously observed that certain atypical antipsychotic drugs reduce the
      amplitude and duration of miniature end-plate currents (EPCs) at the frog
      neuromuscular junction (Effects of atypical antipsychotics on vertebrate
      neuromuscular transmission, Nguyen, Q.-T., Yang, J., Miledi, R. Neuropharmacology
      42, 2002, 670-676), therefore suggesting that these drugs act on nicotinic
      acetylcholine receptors. In this study we examined the effects of the atypical
      antipsychotic clozapine on nicotinic receptors of frog neuromuscular end-plates
      or in Xenopus oocytes expressing the alpha(1)beta(1)gamma delta mouse skeletal
      muscle nicotinic receptor. At neuromuscular junctions, postsynaptic currents were
      reduced by micromolar concentrations of clozapine. This compound also acted
      presynaptically by increasing the quantal content of EPCs of muscles without
      noticeably affecting paired-pulse facilitation. In oocytes, clozapine inhibited
      alpha(1)beta(1)gamma delta receptors with an IC(50) of 10 microM and a Hill
      coefficient of 1. Blockage of alpha(1)beta(1)gamma delta receptors by clozapine
      bears several hallmarks of open-channel blockers, including faster response
      decays, strong voltage dependence of the block, large rebound currents upon wash,
      and reduction of peak responses even at saturating concentrations of
      acetylcholine. However, clozapine increased the EC(50) for acetylcholine and its
      blocking effect was enhanced by preincubation. These results suggest that
      clozapine antagonizes muscle nicotinic receptors by blocking open channels, and
      possibly also by another mechanism which still remains to be investigated.

PMID- 11985825
TI  - Effects of atypical antipsychotics on vertebrate neuromuscular transmission.
AB  - A study was made of the effects of the atypical antipsychotics clozapine,
      olanzapine, sulpiride and risperidone on nicotinic synaptic transmission at the
      frog neuromuscular junction. At concentrations higher than 10 microM, these
      atypical antipsychotics partially reduced the amplitude of miniature end-plate
      currents (mEPCs) in a dose-dependent and reversible manner. Atypical
      antipsychotics were, however, less effective than typical neuroleptics of the
      phenothiazine family at inhibiting mEPCs. In addition to decreasing mEPC
      amplitude, the atypical antipsychotics reduced the half-decay time of mEPCs. In
      the case of clozapine, the reduction in mEPC amplitude and duration was not
      markedly voltage-dependent. Beside their post-synaptic effects, all atypical
      neuroleptics, except sulpiride, increased the frequency of mEPCs in a
      concentration-dependent manner, with the strongest effect seen with clozapine.
      Altogether, these results raise the possibility that atypical neuroleptics could
      derive some of their therapeutic effects not only from their well-known
      inhibitory action on dopaminergic receptors, but also from their pre- and post
      synaptic modulation of nicotinic neurotransmission.

PMID- 11985826
TI  - Stereospecific blockade of marble-burying behaviour in mice by selective, non
      peptidergic neurokinin1 (NK1) receptor antagonists.
AB  - By analogy with the selective serotonin reuptake inhibitor, fluvoxamine, and the
      tricyclic agent, clomipramine, the novel, selective, non-peptidergic NK(1)
      receptor antagonist, GR205,171, dose-dependently and completely blocked marble
      burying behaviour in mice: Inhibitory Dose(50)s (ID(50)s), 4.5, 4.8 and 7.6
      mg/kg, respectively. In contrast to GR205,171, its isomer, GR226,206, which
      displays substantially lower affinity for NK(1) receptors, was inactive (> 40.0
      mg/kg). By analogy with GR205,171, a further, selective NK(1) antagonist,
      RP67,580, abolished marble-burying behaviour with an ID(50) of 11.9 mg/kg. At
      doses significantly reducing marble-burying behaviour, GR205,171 and RP67,580
      little influenced motor behaviour. In conclusion, like fluvoxamine and
      clomipramine, selective, non-peptidergic NK(1) receptor antagonists block marble
      burying in mice. Although the biological bases of this behaviour remain unclear,
      these observations underpin the contention that NK(1) receptors may be implicated
      in affective disorders.

PMID- 11985827
TI  - Developmental regulation of alpha 1A-adrenoceptor function in rat brain
      oligodendrocyte cultures.
AB  - In this study, we examined the effect of norepinephrine (NE) on
      phosphatidylinositol-4,5-bisphosphate (PI) hydrolysis in progenitors and
      differentiated oligodendrocytes. NE caused a time- and concentration-dependent
      increase in total inositol phosphate (IP(t)) formation. The magnitude of this
      response increased as oligodendrocytes matured and was accompanied with an
      increase in alpha(1)-adrenoceptor (alpha(1)-AR) levels. To pharmacologically
      characterize the alpha(1)-AR subtype mediating PI hydrolysis in 12-day
      differentiated oligodendrocytes, various selective antagonists were used.
      Prazosin, the non-selective 1-AR antagonist, blocked NE-mediated IP(t) formation.
      Similarly, the alpha(1A)-AR selective competitive antagonists, 5-methyl urapidil
      (5-MU) and WB4104, were potent blockers of NE-mediated IP(t) formation. In
      contrast, the alpha(1B)- and alpha(1D)-AR antagonist, chloroethylclonidine and
      the alpha(1D)-AR antagonist, BMY 7378, had no effect. These results suggest that
      NE-induced PI hydrolysis in differentiated oligodendrocytes was mediated through
      the alpha(1A)-AR. Furthermore, this response was prevented by EGTA and CdCl(2),
      suggesting a requirement for extracellular calcium. The presence of alpha(1)-AR
      subtypes in oligodendrocytes was confirmed by reverse transcriptase coupled
      polymerase chain reaction and by immunoprecipitation, with subtype specific
      antibodies. The results indicated that mRNA and protein for the alpha(1A)-,
      alpha(1B)- and alpha(1D)-AR subtypes were expressed. In conclusion, our findings
      show that oligodendrocytes express all three alpha(1)-AR subtypes but that only
      the alpha(1A)-AR was involved in NE-mediated IP(t) formation.

PMID- 11985828
TI  - Presence of alpha-1 adrenoreceptors on thermosensitive neurons in the medial
      preoptico-anterior hypothalamic area in rats.
AB  - Earlier microinjection studies showed that norepinephrine in the medial preoptico
      anterior hypothalamic area (mPOAH) regulates body temperature and the action is
      mediated through alpha-1 adrenoceptors. This study was conducted to confirm if
      the thermosensitive neurons in the mPOAH of rats possess alpha-1 adrenoceptors.
      First, the thermosensitivity of mPOAH neurons was tested and then the effects of
      microiontophoretic application of prazosin, alpha 1 adrenoceptor antagonist, on
      the firing rate of both the thermosensitive as well as the insensitive neurons
      were recorded. Prazosin significantly inhibited the firing rate of the
      thermosensitive neurons suggesting that most of the cold and warm sensitive
      neurons in the mPOAH possess alpha-1 adrenoceptors. These results at the single
      neuronal level confirm our earlier hypothesis that in the mPOAH, norepinephrine
      regulates body temperature by acting on alpha-1 adrenoceptors. The data also
      suggest that sensitivity of the mPOAH neurons to norepinephrine alter with
      changes in body temperature. The detailed physiological significance of the
      results with special reference to thermoregulation at the single neuronal level
      has been discussed.

PMID- 11985829
TI  - An alpha-mercaptoacrylic acid derivative (PD150606) inhibits selective motor
      neuron death via inhibition of kainate-induced Ca2+ influx and not via calpain
      inhibition.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by selective motor neuron death. The exact mechanism responsible for this
      selectivity is not clear, although it is known that motor neurons are very
      sensitive to excitotoxicity. This high sensitivity is due to a high density of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors on
      their surface and to a limited Ca(2+) buffering capacity. Ca(2+) can enter the
      cell upon stimulation through voltage-operated Ca(2+) channels and through the
      Ca(2+)-permeable portion of AMPA receptors. How this Ca(2+) kills motor neurons
      is incompletely understood. In the present study, we report that kainate (KA)
      induced motor neuron death is purely mediated through Ca(2+) entering motor
      neurons through Ca(2+)-permeable AMPA receptors and that voltage-operated Ca(2+)
      channels play no significant role. In contrast to what has been observed in other
      neuronal models or after N-methyl-D-aspartate stimulation, NO synthase inhibition
      and a number of antioxidants did not protect motor neurons from KA-induced death.
      Only PD150606, derived from alpha-mercaptoacrylic acid and considered as a
      selective calpain antagonist, inhibited dose-dependently the KA-induced motor
      neuron death. However, other calmodulin and calpain inhibitors were not
      effective. At least part of the inhibitory effect of PD150606 is due to an
      irreversible inhibition of the Ca(2+) influx through the Ca(2+)-permeable AMPA
      receptor. These results demonstrate the interesting property of PD150606 to
      interfere with excitotoxicity-dependent motor neuron death and show that PD150606
      is not an exclusive calpain/calmodulin antagonist.

PMID- 11985830
TI  - Prostaglandin E1 protects cultured spinal neurons against the effects of nitric
      oxide toxicity.
AB  - The effects of prostaglandin (PG) E(1) on NO neurotoxicity were examined using
      rat cultured spinal neurons. Rat cultured spinal neurons exposed to the NO donor,
      2,2'-(hydroxynitrosohydrazono) bis-ethanamine (NOC18), showed neurotoxic effects
      that were accompanied by apoptotic nuclear change, free radical generation, a
      reduction in glutathione, and mitochondrial dysfunction. PGE(1), at
      concentrations of 1-100 nM, protected cultured spinal neurons from NO toxicity by
      reversing the oxidative and pro-apoptotic properties elicited by NOC18 exposure.
      The administration of PGE(1) increased the intracellular cyclic AMP (cAMP) levels
      in cultured spinal neurons. In addition, reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis confirmed the existence of EP4, a cAMP-elevating PGE
      receptor, in cultured spinal neurons. The protective effects of PGE(1) against NO
      neurotoxicity was partially blocked by an inhibitor of MEK [the mitogen-activated
      protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase],
      suggesting that the MAPK/ERK pathway may play a significant role in the activity
      of PGE(1). PGE(1) up-regulated the expression of the anti-apoptotic protein, Bcl
      2, as determined by Western blot analysis. PGE(1) also induced the expression of
      thioredoxin in cultured spinal neurons. Our data indicate that PGE(1) exerts a
      protective action against NO neurotoxicity in cultured spinal neurons, and
      suggests a therapeutic potential of PGE(1) against spinal cord disease, such as
      amyotrophic lateral sclerosis.

PMID- 11985831
TI  - The peroxisome proliferator-activated receptor alpha-selective activator
      ciprofibrate upregulates expression of genes encoding fatty acid oxidation and
      ketogenesis enzymes in rat brain.
AB  - Activated peroxisome proliferator activated receptor alpha (PPAR alpha) protects
      against the cellular inflammatory response, and is central to fatty acid-mediated
      upregulation of the gene encoding the key ketogenic enzyme mitochondrial 3
      hydroxy-3-methylglutaryl-CoA synthase (mHS). We have previously demonstrated both
      PPAR alpha and mHS expression in brain, implying that brain-targeted PPAR alpha
      activators may likewise up-regulate mHS expression in brain. Thus, to attempt
      pharmacological activation of brain PPAR alpha in vivo, we have administered to
      rats two drugs with previously defined actions in rat brain, namely the PPAR
      alpha-selective activator ciprofibrate and the pan-PPAR activator valproate.
      Using the sensitive and discriminatory RNase protection co-assay, we demonstrate
      that both ciprofibrate and valproate induce mHS expression in liver, the
      archetypal PPAR alpha-expressing organ. Furthermore, ciprofibrate potently
      increases mHS mRNA abundance in rat brain, together with lesser increases in two
      other PPAR alpha-regulated mRNAs. Thus we demonstrate, for the first time, up
      regulation of expression of PPAR alpha-dependent genes including mHS in brain,
      with implications in the increased elimination of neuro-inflammatory lipids and
      concomitant increased production of neuro-protective ketone bodies.

PMID- 11985832
TI  - Suppression of experimental autoimmune neuritis by ABR-215062 is associated with
      altered Th1/Th2 balance and inhibited migration of inflammatory cells into the
      peripheral nerve tissue.
AB  - The therapeutic effects of ABR-215062, which is a new immunoregulator derived
      from Linomide, have been evaluated in experimental autoimmune neuritis (EAN), a
      CD4(+) T cell-mediated animal model of Guillain-Barre syndrome in man. In
      previous studies, we reported that Linomide suppressed the clinical EAN and
      myelin antigen-reactive T and B cell responses. Here EAN induced in Lewis rats by
      inoculation with peripheral nerve myelin P0 protein peptide 180-199 and Freund's
      complete adjuvant was strongly suppressed by ABR-215062 administered daily
      subcutaneously from the day of inoculation. ABR-215062 dose-dependently reduced
      the incidence of EAN, ameliorated clinical signs and inhibited P0 peptide 180-199
      specific T cell responses as well as also the decreased inflammation and
      demyelination in the peripheral nerves. The suppression of clinical EAN was
      associated with inhibition of the inflammatory cytokines IFN-gamma and TNF-alpha,
      as well as the enhancement of anti-inflammatory cytokine IL-4 in lymph node cells
      and periphery nerve tissues, respectively, in a dose-dependent manner. These
      effects indicate that ABR-215062 may mediate its effects by regulation of Th1/Th2
      cytokine balance and suggest that ABR-215062 is potentially a new chemical entity
      for effective treatment of autoimmune diseases.

PMID- 11985833
TI  - Asymmetry in facial expression of emotions by chimpanzees.
AB  - Asymmetries in human facial expressions have long been documented and
      traditionally interpreted as evidence of brain laterality in emotional behavior.
      Recent findings in nonhuman primates suggest that this hemispheric specialization
      for emotional behavior may have precursors in primate evolution. In this study,
      we present the first data collected on our closest living relative, the
      chimpanzee. Objective measures (hemimouth length and area) and subjective
      measures (human judgements of chimeric stimuli) indicate that chimpanzees' facial
      expressions are asymmetric, with a greater involvement of the left side of the
      face in the production of emotional responses. No effect of expression type
      (positive versus negative) on facial asymmetry was found. Thus, chimpanzees, like
      humans and some other nonhuman primates, show a right hemisphere specialization
      for facial expression of emotions.

PMID- 11985834
TI  - Intact artificial grammar learning in patients with cerebellar degeneration and
      advanced Parkinson's disease.
AB  - In an artificial grammar learning task, subjects were asked to memorise short
      lists of letter strings formed according to complex rules for letter order. After
      an interval they were unexpectedly asked to discriminate new grammatical strings
      from strings which used the same letters but violated the sequential constraints
      of the grammar. Artificial grammar learning can be mastered successfully by
      amnesic patients and is considered to be an implicit learning task independent of
      declarative learning and memory mechanisms. In this study, 10 patients with
      cerebellar degeneration (CD), 21 Parkinson's disease (PD) and 15 control subjects
      were tested on artificial grammar learning. Additionally PD patients with
      advanced disease were examined under adequate medication and dopaminergic
      withdrawal. All patient groups showed intact artificial grammar learning. Neither
      cerebellar damage nor basal ganglia dysfunction nor dopaminergic medication
      impairs or affects artificial grammar learning. Although the patients showed
      significant executive dysfunction, implicit learning remains intact. The
      conclusion is that cerebellar and basal ganglia circuits play no essential part
      in this kind of implicit learning. The results suggest that artificial grammar
      learning is a cortically mediated function comparable to the mechanism of visual
      priming.

PMID- 11985835
TI  - A callosal transfer deficit in children with developmental language disorder.
AB  - Twenty-two control children (aged 6-12 years) and forty-three children with
      developmental language disorder (DLD) (aged 7-12 years) received a test of
      callosal transfer of tactile information. Among the children with dysphasia, 30
      had a diagnosis of receptive dysphasia and 13 of expressive dysphasia. Both
      control children and children with DLD made a significantly larger number of
      errors in the crossed localization condition (implying callosal transfer of
      tactile information) versus the uncrossed localization condition. In the crossed
      localization condition, children with DLD made a significantly larger number of
      errors than controls, while no differences were found in the two groups of
      children with DLD. These data suggest that the corpus callosum may be involved in
      the pathogenesis of DLD.

PMID- 11985836
TI  - Lexical processing of vocabulary class in patients with Broca's aphasia: an event
      related brain potential study on agrammatic comprehension.
AB  - This paper presents electrophysiological evidence of an impairment in the on-line
      processing of word class information in patients with Broca's aphasia with
      agrammatic comprehension. Event-related brain potentials (ERPs) were recorded
      from the scalp while Broca patients and non-aphasic control subjects read open-
      and closed-class words that appeared one at a time on a PC screen. Separate
      waveforms were computed for open- and closed-class words. The non-aphasic control
      subjects showed a modulation of an early left anterior negativity in the 210
      325ms as a function of vocabulary class (VC), and a late left anterior negative
      shift to closed-class words in the 400-700ms epoch. An N400 effect was present in
      both control subjects and Broca patients. We have taken the early
      electrophysiological differences to reflect the first availability of word
      category information from the mental lexicon. The late differences can be related
      to post-lexical processing. In contrast to the control subjects, the Broca
      patients showed no early VC effect and no late anterior shift to closed-class
      words. The results support the view that an incomplete and/or delayed
      availability of word-class information might be an important factor in Broca's
      agrammatic comprehension.

PMID- 11985837
TI  - The contribution of visual areas to speech comprehension: a PET study in cochlear
      implants patients and normal-hearing subjects.
AB  - Early visual cortex can be recruited by meaningful sounds in the absence of
      visual information. This occurs in particular in cochlear implant (CI) patients
      whose dependency on visual cues in speech comprehension is increased. Such cross
      modal interaction mirrors the response of early auditory cortex to mouth
      movements (speech reading) and may reflect the natural expectancy of the visual
      counterpart of sounds, lip movements. Here we pursue the hypothesis that visual
      activations occur specifically in response to meaningful sounds. We performed PET
      in both CI patients and controls, while subjects listened either to their native
      language or to a completely unknown language. A recruitment of early visual
      cortex, the left posterior inferior temporal gyrus (ITG) and the left superior
      parietal cortex was observed in both groups. While no further activation occurred
      in the group of normal-hearing subjects, CI patients additionally recruited the
      right perirhinal/fusiform and mid-fusiform, the right temporo-occipito-parietal
      (TOP) junction and the left inferior prefrontal cortex (LIPF, Broca's area). This
      study confirms a participation of visual cortical areas in semantic processing of
      speech sounds. Observation of early visual activation in normal-hearing subjects
      shows that auditory-to-visual cross-modal effects can also be recruited under
      natural hearing conditions. In cochlear implant patients, speech activates the
      mid-fusiform gyrus in the vicinity of the so-called face area. This suggests that
      specific cross-modal interaction involving advanced stages in the visual
      processing hierarchy develops after cochlear implantation and may be the
      correlate of increased usage of lip-reading.

PMID- 11985838
TI  - Stroop interference and negative priming in patients with multiple sclerosis.
AB  - The experiment reported represents a preliminary assessment of the ability of
      multiple sclerosis (MS) patients to inhibit distracting stimuli in a selective
      attention task. Twenty MS and 20 matched control participants were given a card
      version of the Stroop colour-word interference task. Four conditions were
      included; neutral (strings of coloured Xs), congruent (colour and word matched),
      Stroop interference (colour and word conflicted) and ignored repeated (again,
      conflicting colour and words, but colour on trial n matched the word on trial n
      1). Response times (RTs) to 30 trials in each condition were measured to the
      nearest second. Increased Stroop interference scores were evident for the MS
      patients relative to the control group. However, a negative priming effect was
      evident for both MS and control groups; RTs were longer for the ignored repeated
      condition relative to the Stroop interference condition. This suggests that both
      groups were able to inhibit distractors on trial n-1, and that increased Stroop
      interference scores, for MS patients were not due to a complete breakdown of
      inhibitory processing. Although negative priming effects did not differ across
      the groups, the possibility of a partial breakdown in inhibitory processes could
      not be ruled out. Other explanations for increased Stroop interference in MS
      patients are also briefly considered.

PMID- 11985839
TI  - Task-dependent differences in the exploratory behaviour of patients with spatial
      neglect.
AB  - The present study analysed task-dependent effects on the exploratory behaviour of
      neglect patients during their spontaneous search of the surroundings. We were
      asking whether different tasks would be associated with different structuring of
      the visual display and, therefore, would result in different forms of neglect in
      one and the same brain-damaged subjects. Neglect patients' eye and head movements
      were recorded when they searched for a target within a homogeneous stimulus array
      surrounding the subjects. Subsequently, they explored the same array which was
      now segmented into different areas. When the patients' attention was allocated to
      the whole surrounding space, all patients completely neglected the left hemispace
      and spontaneously attended to the right hemispace. No significant left-right
      asymmetry was detected in a selected segment located in the periphery of the
      attended, right hemispace. However, all patients completely ignored the left part
      of this segment when they had to concentrate visual search on this segment alone.
      The results suggest an important influence of task-dependent effects on the
      exploratory behaviour of neglect patients. They show that one and the same
      physical stimulus at one and the same location in a scene might be attended or,
      in another situation, neglected, just depending on the behavioural goal of the
      subject. The findings support the idea that the brain organises and reorganises
      continuously the representation of the same physical input according to the
      changing task requirements.

PMID- 11985840
TI  - Sustained attention deficit in bipolar disorder is not a working memory
      impairment in disguise.
AB  - Euthymic patients with bipolar disorder have been reported to show persistent
      deficits in sustained attention. However, the sustained attention task which was
      used also placed demands on working memory. Bipolar disorder patients in the
      euthymic state were therefore compared with healthy controls on two measures of
      sustained attention with and without a working memory component. Signal detection
      methodology was applied to the results. Euthymic patients with bipolar disorder
      were particularly impaired at detecting targets in the sustained attention task
      without a working memory component. This deficit was still apparent in a sub
      group of patients who were not currently receiving lithium medication. By
      contrast, performance in the sustained attention task involving working memory
      task was not significantly different in the two groups. Sustained attention
      deficits apparent during the euthymic period of bipolar disorder cannot be
      explained in terms of working memory impairment and represents a reduced inherent
      capacity rather than a change in response bias. Deficits in sustaining attention
      may help explain the difficulties in psychological and occupational functioning
      in bipolar disorder patients during remission.

PMID- 11985841
TI  - Effect of age of onset of temporal lobe epilepsy on the severity and the nature
      of preoperative memory deficits.
AB  - The nature and severity of pre-operative memory deficits observed in unilateral
      temporal lobe epilepsy depend upon a number of variables. Among these variables,
      age of seizure onset seems to be important. The age at which the lesion is
      sustained could modify the normal functional organization of the brain. Many
      studies have examined the effect of age of onset on the severity of memory
      deficits but have seldom focused on the nature of such deficits
      (verbal/nonverbal) as a function of epileptic focus laterality. This study
      investigates the effect of age of onset on the nature and severity of memory
      impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20
      normal subjects were administered a neuropsychological evaluation. Four groups of
      patients were constituted: left or right temporal lobe epilepsy with early (0-5
      years) or late (10 years and over) age of seizure onset. The early group showed
      major verbal and nonverbal memory deficits. The late group presented minor
      specific deficits: essentially verbal deficits with left temporal lobe seizures
      and nonverbal deficits with right temporal lobe seizures. These results may be
      interpreted in the framework of ontogenesis theories of hemispheric
      specialization.

PMID- 11985842
TI  - Cerebral hemispheric differences in memory of emotional and non-emotional words
      in normal individuals.
AB  - The present study was designed to examine the cerebral hemispheric differences in
      memory of positive, negative and non-emotional words using a new method of
      successive presentation to each visual half-field in which perception of each
      item was nearly perfect thereby allowing laterality differences for effects of
      emotion on memory to emerge unconfounded by perception (Experiment 1). This
      procedure was compared with traditional perceptual identification (Experiment 2).
      In Experiment 1, 12 words were presented successively in each half field in each
      trial followed by free recall at the end of the trial. The results showed that
      recall of positive and negative emotional words was better than that of non
      emotional words in both visual fields. Recall of positive and negative emotional
      words was not different in left and right visual fields (RVFs) although the
      recall of non-emotional words was better in the RVF than in the left visual field
      (LVF). The differences in recall between emotional and non-emotional words was
      greater in the LVF than in the RVF. Experiment 2 used the more traditional method
      of perceptual identification following each visual half-field presentation of a
      single item. Perceptual identification was better in the RVF than the LVF in each
      word condition. There were no visual field differences in perceptual
      identification between emotional and non-emotional words, as there was for memory
      in Experiment 1. The results supported the hypothesis that explicit memory for
      emotional words was dependent more on the right hemisphere, whereas perception of
      both emotional and non-emotional words was more dependent on the left hemisphere.

PMID- 11985843
TI  - Category-specific naming deficits for objects and actions: semantic attribute and
      grammatical role hypotheses.
AB  - Research on category-specific naming deficits and on noun and verb naming has
      raised questions about how organization of knowledge in the brain impacts word
      retrieval. The semantic attribute hypothesis posits that lexical access is
      mediated by brain systems that process the most definitive attributes of specific
      concepts. For example, it has been suggested that the most definitive attribute
      of living things is their visual form, whereas the most definitive attribute of
      non-living things is their function. The competing grammatical role hypothesis
      posits that access to a word depends on the grammatical role it plays in a
      sentence. Since nouns and verbs have different roles, it is assumed that the
      brain uses different systems to process them. These two hypotheses were tested in
      experimental subjects who had undergone left anterior temporal lobectomy (LATL)
      or right anterior temporal lobectomy (RATL) by assessing confrontation naming of
      living things, tools/implements, non-human actions, and human actions. The names
      of living things and implements are nouns and the names of actions are verbs.
      Within each grammatical class, items were characterized either predominantly by
      visual attributes (living things and non-human actions) or by attributes related
      to human activity (implements and human actions). Our results support the
      semantic attribute hypothesis. Patients with LATL were worse at naming
      tools/implements and human actions than RATL patients. Dysfunction in or removal
      of the left anterior temporal lobe disrupts fronto-temporal connections from the
      uncinate fasciculus. These connections may mediate activation of action-related
      information (i.e. movement plan and/or motor use) that facilitates the retrieval
      of names for tools/implements and human actions.

PMID- 11985844
TI  - Fast responses to neglected targets in visual search reflect pre-attentive
      processes: an exploration of response times in visual neglect.
AB  - AE is a patient who suffered a right hemisphere stroke resulting in visual
      neglect symptoms. In the first experiment, AE neglected a single visual target
      that was present in half of the trials and appeared in variable and unpredictable
      positions on the computer screen. The contrast of the target to the screen's
      background was also varied. AE demonstrated severe neglect for left-sided
      targets, and yet his RTs to targets reported incorrectly as absent were faster
      than correct rejections and even right-sided hits. AEs fast "neglect" responses
      seem to indicate that the target was detected but that he remained unaware of its
      presence. Counter intuitively, his fast misses got faster as the discriminability
      of the target decreased. The possibility that fast responses to neglected targets
      reflected a guessing strategy, used proportionally to the degree of uncertainty
      of a target presence, was examined. AEs fast misses were indeed faster at lower
      level of contrast of the stimulus, but his error rate did not tend to approach
      the chance level as the guessing model would predict. In a second experiment, AE
      searched for the letter Z, present on half of the trials, among variable sets of
      distractor letters. In one condition the distractors were all O's and therefore
      differed from the target by an elementary feature. In the other condition, the
      distractors were various letters that differed from the target by combinations of
      features. The key finding was that fast responses to neglected targets occurred
      only in the simple feature search task and not in the complex features
      (conjunction) task. We interpret these findings as indicating that AEs pre
      attentive processing can detect pop-out targets on the left-hand side, but that
      the attentional search is faulty and is aborted early. Hence, the patient's
      attentional system has an "early start" when "pop-out" forms are present, but can
      also fail to "grab" the detected target; consequently, by not attending to a
      stimulus, the patient remains unaware of its presence and will quickly respond
      "no" to present targets.

PMID- 11985845
TI  - A tomato enzyme catalyzing the phosphorylation of 3,4-dihydroxy-2-butanone.
AB  - A riboflavin biosynthesis ribB mutant of Escherichia coli deficient of 3,4
      dihydroxy-2-butanone 4-phosphate synthase was complemented with a cDNA library
      from Lycopersicon esculentum. The complementing gene was isolated and expressed
      in E. coli. The resulting protein was shown to specify a 62 kDa protein which
      phosphorylates dihydroxyacetone, both enantiomers of 3,4-dihydroxy-2-butanone,
      and several other aldoses and ketoses. Sequence analysis revealed homology to
      dihydroacetone kinases (dak) genes from plants, animals, fungi and some
      eubacteria. Genes with similarity to the 5' part of the dak gene from tomato were
      found in many other eubacteria. The physiological role of the dak gene is still
      incompletely known.

PMID- 11985846
TI  - Biosynthesis of the sesquiterpene germacrene D in Solidago canadensis: 13C and
      (2)H labeling studies.
AB  - The biogenetic origin of the isoprenoid building blocks of the sesquiterpene
      germacrene D was studied in Solidago canadensis. Feeding experiments were carried
      out with 1-[5,5-D(2)]deoxy-D-xylulose-5-phosphate (D(2)-DOXP), [5
      13C]mevalonolactone (13C-MVL) and [1-13C]-D-glucose. The hydrodistillate of a cut
      shoot fed with D(2)-DOXP was investigated by enantio-MDGC-MS and the volatile
      fraction of a shoot supplied with 13C-MVL was examined by GC-C-IRMS. The
      incorporation of [1-13C]-D-glucose was analyzed by quantitative 13C NMR
      spectroscopy after isolation of germacrene D from the essential oil. Our labeling
      studies revealed that the biosynthesis of the C-15 skeleton of sesquiterpene
      germacrene D in Solidago canadensis proceeds predominantly via the
      methylerythritol phosphate pathway.

PMID- 11985847
TI  - The amino acid precursors and odor formation in society garlic (Tulbaghia
      violacea Harv.).
AB  - Identification and isolation of (R(S)R(C))-S-(methylthiomethyl)cysteine-4-oxide
      from rhizomes of Tulbaghia violacea Harv. is reported. The structure and absolute
      configuration of the amino acid have been determined by NMR, MALDI-HRMS, IR, and
      CD spectroscopy. Its content varied in different parts of the plant (rhizomes,
      leaves, and stems) between 0.12 and 0.24 mg g(-1) fr. wt, being almost equal in
      the stems and rhizomes. In addition, S-methyl- and S-ethylcysteine derivatives
      have been detected in minute amounts (<3 microg g(-1) fr. wt) in all parts of the
      plant. The enzymatic cleavage of the amino acid and subsequent odor formation are
      discussed. 2,4,5,7-Tetrathiaoctane-4-oxide, the primary breakdown product, has
      been detected and isolated for the first time.

PMID- 11985848
TI  - Ultraviolet induced stress response in fresh cut cantaloupe.
AB  - Changes in the composition of volatile compounds in cantaloupe melon (Cucumis
      melo L. var. reticulatus) as a result of UV induced stress were determined by gas
      chromatography-mass spectrometry (GC-MS). Several volatile ester compounds were
      present, of which twenty-seven were identified in fresh cut cantaloupe. Fruit
      exposure to UV light decreased the concentrations of most of the aliphatic esters
      by over 60% of the amounts present in the corresponding fresh cut fruit. Cyclic
      and acyclic terpenoids, including phytoalexin compounds beta-ionone,
      geranylacetone and terpinyl acetate, were also produced as a result of UV
      exposure for 15 and 60 min, respectively. beta-Ionone, when added to crushed
      cantaloupe (0.01% w/w) completely inhibited microbial growth in the fruit for 24
      h at 20 degrees C. Geranylacetone and terpinyl acetate reduced the microbial
      population from 6.3x10(8) in the untreated control to 1.2x10(8) and 3.5x10(7)
      CFU/g respectively. The results indicate the potential use of UV induced stress
      for screening cantaloupe melon cultivars for disease resistance, and as a minimal
      processing method to extend the shelf life of fresh cut cantaloupe products.

PMID- 11985849
TI  - JM47, a cyclic tetrapeptide HC-toxin analogue from a marine Fusarium species.
AB  - The known metabolite, enniatin B, and a cyclic tetrapeptide, JM47, which is a new
      natural product, were extracted from brown rice cultures of a marine fungus,
      identified as a Fusarium species, isolated from the marine alga Codium fragile.
      NMR studies, including 15N HMQC and 15N HMBC, established the structure of JM47
      as cyclo(Ala-Ala-Aoh-Pro), where Aoh is the amino acid, (2S,9S)-2-amino-8-oxo-9
      hydroxydecanoic acid. The absolute stereochemistry of the Aoh side chain carbinol
      centre was determined using Mosher ester methodology. Analysis of NOESY data
      assisted by molecular modelling revealed an alternating L-, D-, L-, D
      configuration for the tetrapeptide core. The absolute stereochemistry of the core
      was determined by acidic hydrolysis and chiral TLC analysis of the proline
      residue. JM47 belongs to the HC-toxin family of cyclic tetrapeptides which
      possess a 2-amino-8-oxo-9,10-epoxydecanoic acid residue in place of the Aoh unit.
      This is the first report of an analogue of HC-toxin from a marine Fusarium
      species.

PMID- 11985850
TI  - Antiplasmodial activity of naphthoquinones and one anthraquinone from
      Stereospermum kunthianum.
AB  - A lipophilic extract of the root bark of Stereospermum kunthianum revealed
      antiplasmodial activity in vitro. Bioassay-guided fractionation led to the
      isolation of four novel naphthoquinones (sterekunthals A and B, pyranokunthones A
      and B) and one novel anthraquinone (anthrakunthone) together with the known
      naphthoquinone pinnatal. The structures of the novel compounds were determined by
      comprehensive analyses of their 1D and 2D NMR data. The antiplasmodial activities
      and toxicity against the endothelial cell line ECV-304 of the isolated compounds
      have been assessed.

PMID- 11985851
TI  - Cytochalasins Z1, Z2 and Z3, three 24-oxa[14]cytochalasans produced by
      Pyrenophora semeniperda.
AB  - Three new cytochalasans, named cytochalasins Z1, Z2 and Z3, were isolated from
      the wheat culture of Pyrenophora semeniperda, a fungus proposed to biologically
      control grass weeds. Other cytochalasins isolated from the same organic extract
      were identified as the already known cytochalasins F, T, deoxaphomin and
      cytochalasins B, the latter being produced in very large amounts. All three new
      cytochalasins were characterized as 24-oxa[14]cytochalasans by extensive use of
      NMR and MS techniques. Cytochalasins Z1 and Z2 proved to be structurally related
      to cytochalasin T, whereas cytochalasin Z3 was related to cytochalasin B. When
      assayed on wheat and tomato seedlings, cytochalasin Z3, in comparison to the new
      cytochalasins, cytochalasin B, its 21,22-dihydroderivative, cytochalasin F and
      deoxaphomin showed a remarkable ability to inhibit root elongation. The
      possibility of using these metabolites in biological control strategies is
      discussed.

PMID- 11985852
TI  - Diterpenoids from Isodon enanderianus.
AB  - Four ent-kauranoids, 6-epiangustifolin and enanderinanins F-H, as well as 11
      known ent-kaurane diterpenoids, macrocalin B, xerophilusin A, trichorabdal A,
      trichorabdal B, effusin, angustifolin, longikaurin D, longikaurin F,
      enanderinanin B, xerophilusin G and shikokianin were isolated from the aerial
      parts of Isodon enanderianus. The new diterpenoids were identified as 6
      epiangustifolin (11alpha-hydroxy-6alpha-methoxy-6,19-epoxy-6,7-seco-ent-kaur-16
      en-15-one-7,20-olide), enanderinanin F (19-acetoxy-6,20:6,11beta-diepoxy-6,7-seco
      ent-kaur-16-en-15-one-1beta,7-olide), enanderinanin G (1beta,6beta,7beta
      trihydroxy-19-acetoxy-16beta-methoxymethyl-7alpha,20-epoxy-ent-kaur-15-one) and
      enanderinanin H (6beta,7beta,14beta-trihydroxy-1alpha,11beta-acetonide-7alpha,20
      epoxy-ent-kaur-16-en-15-one), respectively, on the basis of spectral data,
      especially by 2D NMR techniques. 6-Epiangustifolin showed significant cytotoxic
      activity against K562 cell.

PMID- 11985853
TI  - Dimeric phenylphenalenones from Musa acuminata and various Haemodoraceae species.
      Crystal structure of anigorootin.
AB  - Three fused octacyclic phenylphenalenone dimers were isolated from Musa
      acuminata: Anigorootin, which was first isolated from Anigozanthos flavidus and
      hitherto represented the only compound of that type, the new 4'-hydroxy
      anigorootin, and 4',4"-di-hydroxy-anigorootin, which is a revised structure. The
      crystal structure of anigorootin was determined by X-ray crystallography. 3,3'
      Bis-hydroxyanigorufone, a dimer of the conventional type known from Anigozanthos
      preissii, was also found in Musa acuminata. Phytochemical analysis of several
      Haemodoraceae species revealed the occurrence of anigorootin, 3,3'-bis
      hydroxyanigorufone, and the novel metabolite 3,3'-bis-anigorufone. The occurrence
      of the same compounds in Musaceae and Haemodoraceae indicates the close
      chemotaxonomic relationship of both plant families.

PMID- 11985854
TI  - Patterns of methyl and O-acetyl esterification in spinach pectins: new
      complexity.
AB  - Driselase-digestion of cell walls from suspension-cultures of spinach (Spinacia
      oleracea L.), followed by anion-exchange chromatography, gel-permeation
      chromatography, preparative paper chromatography and preparative paper
      electrophoresis, yielded ten uronic acid-containing products in addition to free
      galacturonic acid (GalA). These included 4-O-methylglucuronic acid, alpha-L
      rhamnopyranosyl-(1-->4)-D-glucuronic acid and several oligosaccharides containing
      GalA residues. The structures were unambiguously determined by a combination of 1
      and 2-dimensional NMR spectroscopic techniques. Five of the six homogalacturonan
      derived oligosaccharides purified contained 3-O-acetyl-GalA residues; however,
      methyl-esterified GalA residues occurred adjacent to both 2-O-acetyl-GalA and 3-O
      acetyl-GalA residues. An acetylated, rhamnogalacturonan-I-derived oligosaccharide
      that was purified also contained 3-O-acetyl-GalA residues. Taken together with
      published data, our findings indicate considerable diversity in the patterns of
      pectin esterification. The implications for the action of pectin esterases are
      discussed.

PMID- 11985855
TI  - Acylated anthocyanins from red radish (Raphanus sativus L.).
AB  - Twelve acylated anthocyanins were isolated from the red radish (Raphanus sativus
      L.) and their structures were determined by spectroscopic analyses. Six of these
      were identified as pelargonidin 3-O-[6-O-(E)-feruloyl-2-O-beta-D-glucopyranosyl]
      (1-->2)-beta-D-glucopyranoside]-5-O-(beta-D-glucopyranoside), pelargonidin 3-O-[6
      O-(E)-caffeoyl-2-O-(6-(E)-feruloyl-beta-D-glucopyranosyl)-(1-->2)-beta-D
      glucopyranoside]-5-O-(beta-D-glucopyranoside), pelargonidin 3-O-[6-O-(E)-p
      coumaroyl-2-O-(6-(E)-caffeoyl-beta-D-glucopyranosyl)-(1-->2)-beta-D
      glucopyranoside]-5-O-(beta-D-glucopyranoside), pelargonidin 3-O-[6-O-(E)-feruloyl
      2-O-(6-(E)-caffeoyl-beta-D-glucopyranosyl)-(1-->2)-beta-D-glucopyranoside]-5-O
      (beta-D-glucopyranoside), pelargonidin 3-O-[6-O-(E)-p-coumaroyl-2-O-(6-(E)
      feruloyl-beta-D-glucopyranosyl)-(1-->2)-beta-D-glucopyranoside]-5-O-(beta-D
      glucopyranoside), and pelargonidin 3-O-[6-O-(E)-feruloyl-2-O-(2-(E)-feruloyl-beta
      D-glucopyranosyl)-(1-->2)-beta-D-glucopyranoside]-5-O-(beta-D-glucopyranoside).

PMID- 11985856
TI  - Structural studies of the pectic polysaccharide from duckweed Lemna minor L.
AB  - The pectic polysaccharide of duckweed Lemna minor L. termed lemnan (LM) was shown
      to contain the ramified, "hairy" region. Using partial acid hydrolysis and Smith
      degradation followed by NMR spectroscopy of the fragments obtained, some
      structural features of the hairy region of LM were elucidated. Partial acid
      hydrolysis of LM afforded the crude polysaccharide fraction LMH that was
      separated into two polysaccharide fractions: LMH-1 and LMH-2. In addition, the
      oligosaccharide fraction LMH-3 contained 97% D-apiose was obtained from the
      supernatant. A further more rigorous acidic hydrolysis of LMH led to the crude
      polysaccharide fraction LMHR which was separated in to two fractions: LMHR-1 and
      LMHR-2. Smith degradation of LMH afforded the polysaccharide fragment LMHS
      differed in low contents of apiose residues. Unfortunately, NMR-spectroscopy
      failed to provide significant evidence concerning the structure of LMH-1 due to
      the complexity of the macromolecule. The structure of the 1H/13C-NMR spectroscopy
      including the correlation 2D NMR spectroscopy. As a result, alpha-1,4-D
      galactopyranosyluronan was confirmed to be the main constituent of the LM
      backbone. In addition, the ramified, "hairy" region of the macromolecule appeared
      to contain segments consisting of residues of terminal and beta-1,5-linked
      apiofuranose, terminal and alpha-1,5-linked arabinofuranose, terminal and beta
      1,3- and beta-1,4- linked galactopyranose, the terminal and beta-1,4-linked
      xylopyranose, and beta-1,4-linked 2-mono-O-methyl xylopyranose. Analytical and
      NMR-spectral data of LMHS confirmed the presence of considerable amounts of the
      non-oxidized of 1,4-linked D-galactopyranosyl uronic acid residues. Thus, some
      side chains of the ramified region of lemnan appeared to attach to D
      galactopyranosyl uronic acid residues of the backbone.

PMID- 11985858
TI  - Development and applications of transgenesis in the yellow fever mosquito, Aedes
      aegypti.
AB  - Transgenesis technology has been developed for the yellow fever mosquito, Aedes
      aegypti. Successful integration of exogenous DNA into the germline of this
      mosquito has been achieved with the class II transposable elements, Hermes,
      mariner and piggyBac. A number of marker genes, including the cinnabar(+) gene of
      Drosophila melanogaster, and fluorescent protein genes, can be used to monitor
      the insertion of these elements. The availability of multiple elements and marker
      genes provides a powerful set of tools to investigate basic biological properties
      of this vector insect, as well as the materials for developing novel, genetics
      based, control strategies for the transmission of disease.

PMID- 11985859
TI  - PSLAP, a protein with multiple adhesive motifs, is expressed in Plasmodium
      falciparum gametocytes.
AB  - A gene coding for a protein containing two Scavenger Receptor Cysteine-Rich
      (SRCR) motifs, four Limulus factor C, Coch-5b2 and Lgl1 (LCCL) motifs; and one
      Polycystin-1, Lipoxygenase and Alpha Toxin (PLAT) motif was cloned from
      Plasmodium chabaudi and homologues identified in the P. falciparum and P. yoelii
      genome data bases. At least one of these sequence motifs (SRCR) has adhesive
      properties in other proteins, therefore, we propose to name this protein PSLAP
      for Plasmodium SRCR, LCCL Adhesive-like Protein. Southern blotting and chromosome
      analysis showed that pslap is a single copy gene on chromosome 14 in P.
      falciparum 3D7. pslap mRNA is strongly expressed in P. falciparum gametocytes,
      but was undetectable on Northern blots of RNA from the asexual blood stages.
      Polyclonal antibodies raised to different parts of PSLAP detected a protein
      expressed in late gametocytes, but not in the early stages of gametocytogenesis
      or asexual blood stages of P. falciparum. We suggest that PSLAP functions in the
      mosquito, for example, in modulation of the invertebrate host immune response or
      in protection against complement factors in the blood meal.

PMID- 11985860
TI  - Antibodies raised against receptor-binding domain of Plasmodium knowlesi Duffy
      binding protein inhibit erythrocyte invasion.
AB  - Erythrocyte invasion by malaria parasites requires specific receptor-ligand
      interactions. Plasmodium vivax and Plasmodium knowlesi are completely dependent
      on binding the Duffy blood group antigen to invade human erythrocytes. P.
      knowlesi invades rhesus erythrocytes by multiple pathways using the Duffy antigen
      as well as alternative receptors. Plasmodium falciparum binds sialic acid
      residues on glycophorin A as well as other sialic acid-independent receptors to
      invade human erythrocytes. Parasite proteins that mediate these interactions
      belong to a family of erythrocyte binding proteins, which includes the P. vivax
      Duffy binding protein, 175 kDa P. falciparum erythrocyte binding antigen (EBA
      175), P. knowlesi alpha protein, which binds human and rhesus Duffy antigens, and
      P. knowlesi beta and gamma proteins, which bind Duffy-independent receptors on
      rhesus erythrocytes. The receptor-binding domains of these proteins lie in
      conserved, N-terminal, cysteine-rich regions that are referred to as region II.
      Here, we have examined the feasibility of inhibiting erythrocyte invasion with
      antibodies directed against receptor-binding domains of erythrocyte binding
      proteins. Region II of P. knowelsi alpha protein (Pk(alpha)RII), which binds the
      Duffy antigen, was expressed as a secreted protein in insect cells and purified
      from culture supernatants. Rabbit antibodies raised against recombinant
      Pk(alpha)RII were tested for inhibition of erythrocyte binding and invasion.
      Antibodies raised against Pk(alpha)RII inhibit P. knowlesi invasion of both human
      and rhesus erythrocytes. These data provide support for the development of
      recombinant vaccines based on the homologous binding domains of P. vivax Duffy
      binding protein and P. falciparum EBA-175.

PMID- 11985861
TI  - Sequence variation in the dihydrofolate reductase-thymidylate synthase (DHFR-TS)
      and trypanothione reductase (TR) genes of Trypanosoma cruzi.
AB  - Dihydrofolate reductase-thymidylate synthase (DHFR-TS) and trypanothione
      reductase (TR) are important enzymes for the metabolism of protozoan parasites
      from the family Trypanosomatidae (e.g. Trypanosoma spp., Leishmania spp.) that
      are targets of current drug-design studies. Very limited information exists on
      the levels of genetic polymorphism of these enzymes in natural populations of any
      trypanosomatid parasite. We present results of a survey of nucleotide variation
      in the genes coding for those enzymes in a large sample of strains from
      Trypanosoma cruzi, the agent of Chagas' disease. We discuss the results from an
      evolutionary perspective. A sample of 31 strains show 39 silent and five amino
      acid polymorphisms in DHFR-TS, and 35 silent and 11 amino acid polymorphisms in
      TR. No amino acid replacements occur in regions that are important for the
      enzymatic activity of these proteins, but some polymorphisms occur in sites
      previously assumed to be invariant. The sequences from both genes cluster in four
      major groups, a result that is not fully consistent with the current
      classification of T. cruzi in two major groups of strains. Most polymorphisms
      correspond to fixed differences among the four sequence groups. Two tests of
      neutrality show that there is no evidence of adaptive divergence or of selective
      events having shaped the distribution of polymorphisms and fixed differences in
      these genes in T. cruzi. However, one nearly significant reduction of variation
      in the TR sequences from one sequence group suggests a recent selective event at,
      or close to, that locus.

PMID- 11985862
TI  - SmCB2, a novel tegumental cathepsin B from adult Schistosoma mansoni.
AB  - Papain-like cysteine endopeptidases have been recognized as potential targets for
      chemotherapy and serodiagnostic reagents in infections with the human parasitic
      helminth Schistosoma. A novel cathepsin B endopeptidase from adult S. mansoni has
      been isolated and characterized. The enzyme is termed SmCB2 to distinguish it
      from the first recorded schistosome cathepsin B, SmCB1, also known as Sm31. A
      rapid and convenient protocol involving anion exchange and affinity
      chromatography is described for the isolation of SmCB1 and SmCB2 from the same
      parasite starting material. SmCB2 has been functionally expressed in and purified
      from Pichia pastoris. Both native and recombinant SmCB2 migrate similarly (33
      kDa) by SDS-PAGE. Both display strict acidic pH activity profiles and similar
      K(m) and k(cat) for dipeptidyl amidomethylcoumarin substrates. We conclude that
      the recombinant enzyme is properly folded. The S(2) subsite specificity of
      recombinant SmCB2 exhibits the preferences Phe>Leu>Val>>Arg. By immunoblotting
      with anti-SmCB2 IgG, a 33 kDa protein was identified in soluble extracts of male
      schistosomes. By immunohistochemistry, SmCB2 was localized in the tegumental
      tubercles and parenchyma of males with less product being visualized in the
      parenchyma of females. The enzyme may be lysosomal and function at the host
      parasite-interface.

PMID- 11985863
TI  - TbRAB18, a developmentally regulated Golgi GTPase from Trypanosoma brucei.
AB  - The trypanosomal secretory system is broadly similar to that of higher eukaryotes
      as proteins enter the system via the endoplasmic reticulum and are transported to
      the Golgi complex for elaboration of glycan chains. Importantly N-glycan
      processing is stage specific with only the bloodstream form (BSF) processing
      beyond the oligomannose form. Increased complexity of the BSF Golgi apparatus, as
      evidenced by morphological studies, may underpin this higher activity, but few
      trypanosome-specific Golgi proteins have been described that may play a role in
      this developmental alteration. Here we describe a novel member of the T. brucei
      Rab family, TbRAB18, which is stage-regulated and highly expressed in the BSF
      whilst barely detectable in the insect stage. This stage-specific expression
      suggests the presence of a TbRAB18-dependent transport pathway required for
      survival in the mammalian host. Furthermore, data indicate that TbRAB18 localises
      to membranes in close juxtaposition to structures stained with BODIPY-ceramide, a
      Golgi marker. Wild type TbRAB18, ectopically expressed in insect stage cells
      colocalises with TbRAB31, and hence is targeted to the Golgi complex, consistent
      with the location of the endogenous protein in the bloodstream form, whilst GTP
      and GDP-locked mutant isoforms demonstrate distinct localisations, suggesting
      that Golgi-targetting of TbRAB18 is nucleotide-state dependent. We also find that
      ectopic expression of TbRAB18 wild type and mutant isoforms has no detectable
      effect on the synthetic anteriograde trafficking probe, TbBiPN. Finally, the
      location, and hence function, of TbRAB18 are distinct from the closest metazoan
      homologue, murine Rab18; the latter protein is involved in endocytic transport
      pathways whilst clearly TbRAB18 is not. Our data indicate further complexity in
      the evolution of small GTPases, and highlight the need for robust functional data
      prior to assignment of members of complex gene families.

PMID- 11985864
TI  - Genetic and structural heterogeneity of proteophosphoglycans in Leishmania.
AB  - Proteophosphoglycans (PPG) are a large family of extensively glycosylated
      proteins with some unusual and unique features. The ppg gene family is conserved
      in at least three Leishmania species and localises to chromosome 35. Previous
      studies using standard discontinuous SDS-PAGE have been incapable of resolving
      PPG heterogeneity with most material failing to enter the resolving gel. We have
      exploited a continuous electrophoretic system, which allows for the first time
      the separation and characterisation of a low molecular weight population of PPG
      polypeptides. We provide evidence of surface expressed and developmentally
      regulated forms. Among those, we identify for the first time the previously
      described membrane-bound PPG and a form of filamentous fPPG, which is altered, or
      absent in two of the three L. major isolates examined.

PMID- 11985865
TI  - A 24 bp cis-acting element essential for the transcriptional activity of
      Plasmodium falciparum CDP-diacylglycerol synthase gene promoter.
AB  - CDP-diacylglycerol synthase (CDS) is a key rate-limiting enzyme in the
      phospholipid metabolism of Plasmodium falciparum, converting phosphatidic acid to
      CDP-diacylglycerol. The CDS gene is predominantly expressed in the mature
      intraerythrocytic stages. Consequently, we physically and functionally
      characterized the CDS gene promoter. The mRNA transcription initiation site was
      mapped 121 bp upstream of the CDS gene translation start site. A 1909 bp 5'
      upstream sequence was isolated and found to be transcriptionally active thus
      constituting a functional CDS promoter. Mapping of this promoter identified a 44
      bp cis-acting sequence, located between -1640 and -1596 bp upstream of the ATG
      codon, essential for efficient transcriptional activity. This 44 bp sequence
      binds specifically to nuclear factors from trophozoite stage parasites. We
      further showed that a 24 bp element, lying within the 44 bp sequence, mediates
      the specific binding to nuclear proteins and shows no significant homology to
      known eukaryotic DNA consensus sequence elements that bind transcription factors.
      The deletion of the 24 bp element abrogated promoter activity, indicating that
      this cis-acting sequence element is essential for efficient transcription of the
      CDS gene.

PMID- 11985866
TI  - Substrate specificity of schistosome versus human legumain determined by P1-P3
      peptide libraries.
AB  - Asparaginyl endopeptidases, or 'legumains' have been identified and characterized
      in plants, the blood fluke parasite Schistosoma, and mammals. The legumains are a
      novel family of cysteine proteases and display restricted specificity for peptide
      hydrolysis on the carboxyl side of asparagine residues. Two forms of recombinant
      asparaginyl endopeptidase from Schistosoma mansoni (C197 Sm32 and N197C Sm32),
      expressed in Pichia pastoris, have been analyzed for substrate specificity using
      a positional-scanning synthetic combinatorial library (PS-SCL). We first screened
      Sm32 using a P1-diverse library. This library demonstrated the absolute
      specificity of Sm32 for asparagine at P1. To determine the P2-P3 preferences of
      Sm32, we constructed a library with asparagine fixed at P1, and the P2-P3
      positions randomized. The library was screened using the two forms of Sm32, human
      asparaginyl endopeptidase, and to confirm its diversity, cruzain from Trypanosoma
      cruzi. The schistosome legumain showed a preference for P3: Thr>Ala>Val>Ile, and
      P2: Ala>Thr>Val>Asn, with an overall broader specificity at P3 than at P2. Both
      human and schistosome legumain can accommodate Thr and Ala at P2 and P3. However,
      optimal substrate sequences differ, with Sm32 preferring Thr-Ala-Asn, and human
      legumain preferring Pro-Thr-Asn. Predictions of substrate specificity from the
      library screen were confirmed using single peptide substrates for kinetic assays.

PMID- 11985867
TI  - Molecular characterization of a calcium binding translationally controlled tumor
      protein homologue from the filarial parasites Brugia malayi and Wuchereria
      bancrofti.
AB  - We have cloned homologues of the mammalian translationally controlled tumor
      protein (TCTP) from the human filarial parasites Wuchereria bancrofti and Brugia
      malayi. TCTP genes from B. malayi and W. bancrofti were expressed in a T7
      promoter vector as histidine tagged fusion proteins. Both the recombinant B.
      malayi TCTP (rBm-TCTP) and recombinant W. bancrofti TCTP (rWb-TCTP) have a
      molecular mass of approximately 28 kDa with the histidine tag. Sequence analyses
      showed that there is a 98% similarity between the two filarial TCTPs at amino
      acid levels and are immunologically cross-reactive. Analysis of soluble proteins
      from various lifecycle stages of B. malayi suggested that the expression of Bm
      TCTP might be differentially regulated and occurs in multimeric form. Recombinant
      TCTP were found to form multimers in solution under non-reducing conditions. The
      tendency for filarial TCTPs to become multimers was predicted by the presence of
      the Lupas coiled coil structure in their sequence. Despite the absence of a
      signal sequence, Bm-TCTP is present abundantly in the excretory/secretions (ES)
      of microfilariae. Characterization studies showed that both Bm- and Wb-TCTPs are
      calcium-binding proteins and have histamine-releasing function in vitro. When
      injected intraperitoneally both the filarial TCTPs induced inflammatory
      infiltration of eosinophils into the peritoneal cavity of mice suggesting that
      the filarial TCTPs may have a role in the allergic inflammatory responses
      associated with filarial infections.

PMID- 11985868
TI  - Biosynthesis of the major surface protease GP63 of Leishmania chagasi.
AB  - The protozoan Leishmania chagasi expresses a surface metalloprotease, GP63, whose
      abundance increases 14-fold as parasites grow from logarithmic to stationary
      phase. L. chagasi GP63 is encoded by three classes of MSP genes that are
      differentially expressed during parasite growth. Using metabolic labeling and
      immunoprecipitation, we found L. chagasi GP63 first appeared as a 66-kDa band
      that was replaced by a 63-kDa protein. This pattern also occurred in transfected
      L. donovani harboring detectable products of only one MSP gene, suggesting a
      precursor-product relationship. The half-life of GP63 increased from 29 h in
      logarithmic phase to >72 h in stationary phase promastigotes. GP63 loss from the
      cell was complemented by the appearance of a 63-kDa GP63 in extracellular medium
      in both membrane-associated and -free forms. Calculations suggested that the long
      and lengthening T(1/2) of cell-associated GP63 accounts in part for its
      progressive accumulation in the cell during promastigote growth. The current
      findings add yet another level of complexity to post-transcriptionally regulated
      expression of an abundant surface molecule in a trypanosomatid protozoan.

PMID- 11985869
TI  - The disulfide redox system of Schistosoma mansoni and the importance of a
      multifunctional enzyme, thioredoxin glutathione reductase.
AB  - Schistosoma mansoni, a causative agent of schistosomiasis, is a major cause of
      human morbidity in tropical countries. Adult schistosomes, which reside in the
      hepatic portal system, are exposed to reactive oxygen compounds through
      respiration and as a result of the host immune response. To minimize oxidative
      stress schistosomes must possess adequate mechanisms of detoxification. Major
      detoxification systems rely on reducing equivalents from the disulfide
      oxidoreductases glutathione and thioredoxin. Therefore, maintenance of adequate
      levels of these thiols in a reduced form is critical. Here we show that S.
      mansoni possess an unusual thiol redox system centered on thioredoxin glutathione
      reductase. This enzyme represents an unusual fusion of a pyridine nucleotide
      disulfide oxidoreductase with a redox active glutaredoxin extension. Furthermore,
      we predict that this is a selenocysteine protein. Immunoprecipitation, western
      blot and inhibitor studies show that this protein has thioredoxin reductase,
      glutathione reductase, and glutaredoxin activities. Most importantly, we show
      that thioredoxin glutathione reductase appears to be the major, if not the sole
      enzyme for these activities in adult worms, completely replacing thioredoxin
      reductase and glutathione reductase. This is the first example of an organism
      with a redox system based exclusively on thioredoxin glutathione reductase.

PMID- 11985870
TI  - Efficient transposition of preformed synaptic Tn5 complexes in Trypanosoma
      brucei.

PMID- 11985871
TI  - Detection of iNOS gene expression in cutaneous leishmaniasis biopsy tissue.

PMID- 11985872
TI  - RNA interference in trypanosomes transfected with sense and antisense plasmids.

PMID- 11985873
TI  - In vivo expression of ferredoxin in a drug resistant trichomonad increases
      metronidazole susceptibility.

PMID- 11985875
TI  - A Schistosoma mansoni Pad1 homologue stabilizes c-Jun.
AB  - We report the cloning and functional analysis of a Pad1 homologue (SmPOH) from
      Schistosoma mansoni. SmPOH encodes a protein of approximately 35 kDa with high
      amino acid identities to yeast Pad1 (65%) and its human homologue, POH1 (78%).
      Members of the Pad1 family are subunits of the 26S proteasome and have been
      implicated as positive modulators of transcription in yeast. Recombinant SmPOH
      expressed in COS7 cells exhibited a punctate pattern of distribution throughout
      the cytoplasm and nucleus, predominantly in the nuclear periphery, a distribution
      consistent with that of the cellular proteasome. Transient overexpression of
      SmPOH in COS7 cells caused a dose-dependent stimulation in AP-1 transcriptional
      activity, as determined by a reporter gene assay. This effect was associated with
      a pronounced increase in the levels of cellular c-Jun. In vitro degradation
      assays further demonstrated that SmPOH specifically decreased the rate of c-Jun
      degradation in a dose dependent manner. Taken together, these results suggest
      that SmPOH, and possibly other related Pad1 proteins, function as positive
      modulators of transcription by increasing the stability of cellular c-Jun, making
      elevated amounts of this protein available for transactivation of AP-1-responsive
      genes.

PMID- 11985876
TI  - Complementary distribution of vesicular glutamate transporters in the central
      nervous system.
AB  - Two vesicular glutamate transporters (VGluTs) have been identified at the
      molecular level very recently and revealed to possess similar pharmacological
      characteristics for glutamate uptake. Vesicular glutamate transporter 1 (VGluT1),
      which was originally named brain-specific Na+-dependent inorganic phosphate
      cotransporter (BNPI), is mainly expressed in telencephalic regions, whereas
      vesicular glutamate transporter 2 (VGluT2), formerly referred to as
      differentiation-associated Na+-dependent inorganic phosphate cotransporter
      (DNPI), is produced principally in diencephalic and lower brainstem regions.
      Since no other proteins show as high molecular similarity to VGluT1 or VGluT2 as
      the two transporters exhibit, it is likely that the mammalian central nervous
      system use only two gene products for vesicular glutamate uptake. Immunoelectron
      microscopic analysis has revealed that the two VGluTs are located on synaptic
      vesicles in axon terminals making an asymmetric type of synapses, supporting that
      they serve as vesicular transporters in excitatory terminals. Furthermore, mRNA
      and immunoreactivity for VGluTs are distributed largely in a complementary
      fashion to distinct populations of excitatory neurons; for example, in the
      cerebral cortex, thalamocortical axon terminals use VGluT2, whereas excitatory
      axon terminals of corticocortical or intracortical fibers seem to apply VGluT1
      for glutamate uptake. This complementary distribution might suggest that the two
      VGluTs have an as yet unknown difference in functions.

PMID- 11985877
TI  - Reciprocal age-related changes in GAP-43/B-50, substance P and calcitonin gene
      related peptide (CGRP) expression in rat primary sensory neurones and their
      terminals in the dorsal horn of the spinal cord and subintima of the knee
      synovium.
AB  - Age-related changes in the expression of the growth associated protein GAP-43/B
      50, and the neuropeptides substance P and calcitonin gene-related peptide (CGRP)
      were investigated in the sensory neurones of rat dorsal root ganglia, dorsal
      horns of the spinal cord and subintimal knee synovium. The two time-points
      studied were 2 months (young adults) and 14-month (aged)-old Sprague Dawley rats.
      Dorsal root ganglia: In young adults, 40 and 35% of the L4-L5 dorsal root
      ganglion neurones were positive for GAP-43/B-50 with a 1.5 fold increase in
      frequency in aged rats at the L5 ganglion. GAP-43/B-50 was strongly expressed by
      the non-neuronal satellite cells of some medium and many large sized neurones in
      aged rats. There were marked reciprocal shifts between small and medium sized
      sensory neurones in respect to their substance P and CGRP expression profiles.
      Dorsal horn of the spinal cord: there was a 1.3 fold decrease of substance P at
      L5 level and a 1.3 and 1.5 fold decrease of CGRP at L4-L5 levels in aged rats,
      respectively. Synovial membrane: There was a 2.3 fold increase in GAP-43/B-50 and
      a 2.5 fold decrease of CGRP with no changes in substance P expression. These
      results indicate that (i) primary sensory neurones undergo age-related changes
      already in early stages of aging, (ii) aging may result in a reduction of
      substance P and CGRP axonal transport, and (iii) reduced numbers of CGRP
      containing synovial perivascular fibres may imply a deficient regulation of the
      synovial microvasculature and therefore metabolic homeostasis of the joint in
      aged subjects.

PMID- 11985878
TI  - Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells.
AB  - Programmed cell death plays an integral role in neurodegenerative diseases such
      as Alzheimer's disease (AD). Acetylcholinesterase (AChE) was suggested to be
      neurotoxic in vivo and in vitro and accelerate assembly of amyloid peptide into
      Alzheimer's fibrils. In our experiments, we found increased AChE expression in
      apoptotic neuroblastoma SK-N-SH cells after long-term culture. Our results first
      showed that in apoptotic SK-N-SH cells, AChE aggregated in the nucleus and
      suppression of AChE expression with antisense oligonucleotide could save the
      cells from apoptosis. It was also found that caspase-3 activity was parallel with
      AChE activation in apoptotic SK-N-SH cells. These results suggest that AChE plays
      an important role in the procession of neuroblastoma cell apoptosis and favor the
      association between AChE and neuronal apoptosis in AD.

PMID- 11985879
TI  - Bcl-2 expression in thalamus, brainstem, cerebellum and visual cortex of adult
      primate.
AB  - Due to the functional importance of Bcl-2, which acts as an anti-apoptotic
      protein that also affects neural differentiation and adult neurogenesis, we
      undertook a detailed immunohistochemical study of the distribution of this
      protein in the brain of squirrel monkeys. The present study describes findings
      obtained at thalamic, brainstem, cerebellum and visual cortex levels, and the
      data are compared with our previous results gathered in the same species. At
      thalamic level, Bcl-2-positive neurons occur in anterior, rostral intralaminar,
      midline and lateral habenular nuclei. The protein is also expressed in several
      structures associated with the ventricular system, including the subventricular
      zone (SVZ), the subcommissural organ, and the periventricular grey at rostral and
      caudal tips of the fourth ventricle. At brainstem and cerebellar levels, Bcl-2
      positive neurons occur in the dorsal raphe nucleus, inferior olivary complex, and
      in molecular and granular layers of the cerebellum. Finally, neurons of layer IV
      of the striate cortex display a very strong Bcl-2 immunoreactivity that contrasts
      with the poor labeling of neurons in adjacent parastriate and peristriate
      cortices. These finding suggests that Bcl-2 plays a role in the plasticity and
      structural maintenance of various structures in the primate brain and indicate
      that the mitotically active SVZ might be more extended along the rostrocaudal
      axis in primates than in rodents.

PMID- 11985880
TI  - Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation.
AB  - While the role of creatine in preventing muscle (peripheral) fatigue for high
      performance athletes is well understood, its biochemical role in prevention of
      mental (central) fatigue is not. Creatine is abundant in muscles and the brain
      and after phosphorylation used as an energy source for adenosine triphosphate
      synthesis. Using double-blind placebo-controlled paradigm, we demonstrated that
      dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when
      subjects repeatedly perform a simple mathematical calculation. After taking the
      creatine supplement, task-evoked increase of cerebral oxygenated hemoglobin in
      the brains of subjects measured by near infrared spectroscopy was significantly
      reduced, which is compatible with increased oxygen utilization in the brain.

PMID- 11985881
TI  - A mouse with a point mutation in plasma membrane Ca2+-ATPase isoform 2 gene
      showed the reduced Ca2+ influx in cerebellar neurons.
AB  - We analyzed mutant mice showing behavioral defects such as severe tremor, up-and
      down and side-to-side wriggling of neck without coordination, and found that the
      gene causing the defects was located between 46 and 60.55 centimorgans (cM) on
      the mouse chromosome 6. In this region, nucleotide transition of the plasma
      membrane Ca2+-ATPase isoform 2 (PMCA2) gene was found, which caused a glutamic
      acid to change into lysine. Since PMCA2 is expressed in the cerebellum and plays
      an important role to maintain the homeostasis of the intracellular Ca2+ as a Ca2+
      pump, the behavioral defect can be ascribed to the impairment of Ca2+ regulation
      in neurons of the cerebellum. To confirm the defect of Ca2+ homeostasis in the
      mutant mice, we measured high K+-induced changes in intracellular Ca2+
      concentration ([Ca2+]i) in the cerebellar neurons. Contrary to our expectation,
      the extent of the [Ca2+]i increase in all the regions tested in the cerebellar
      slice was far smaller than that of the wild type mice, while the resting [Ca2+]i
      remained almost unaltered. The rate of rise in [Ca2+]i during high K+-induced
      depolarization was significantly reduced, and the extrusion rate of increased
      [Ca2+]i was also reduced. These results suggested that voltage-gated Ca2+
      channels were down-regulated in the mutant mice in order to regulate [Ca2+]i
      toward the normal homeostasis. The behavioral defects may be ascribed to the down
      regulated Ca2+ homeostasis since dynamic changes in [Ca2+]i are important for
      various neuronal functions.

PMID- 11985882
TI  - A chromodomain-containing nuclear protein, MRG15 is expressed as a novel type of
      dendritic mRNA in neurons.
AB  - On the basis of a hypothesis that proteins encoded by the mRNAs that are
      transported to and translated at the dendrites/synapses may play key roles in
      synaptic plasticity, this study reports on attempts to isolate mRNAs which are
      localizing at the dendrites/synapses from mouse cerebellar synaptosomal
      fractions. Among 100 pieces of dendritic mRNA candidates, 10 pieces of mRNAs were
      found to contain the cytoplasmic polyadenylation element (CPE)-like sequences
      which were contained in certain mRNAs translated in dendrites. We next examined
      the issue of whether the CPE-like sequence-containing mRNAs (CPERs) were
      localized in the synapses/dendrites by means of in situ hybridization. The
      findings indicate that CPER9 was actually localized at the apical dendrites of a
      portion of cerebral cortex layer V pyramidal cells, as well as at the proximal
      dendrites of some of the cerebellar Purkinje cells. CPER9 was found to encode a
      mouse homolog of MRG15, a nuclear protein which contains a chromodomain
      identified in several proteins that act as regulators of transcription.
      Immunohistochemistry with anti-MRG15 antibodies revealed that MRG15 was localized
      in dendrites as well as in the nuclei of Purkinje cells. These results suggest
      that MRG15 may serve as a link between synaptic activity and gene expression.

PMID- 11985883
TI  - Neuronal expression of arylalkylamine N-acetyltransferase (AANAT) mRNA in the rat
      brain.
AB  - The role of arylalkylamine N-acetyltransferase (AANAT) in neuronal functioning
      has been suggested based on biochemical assays; only scarce evidence indicates
      neuronal expression of the mRNA encoding for this enzyme that catalyzes the
      conversion of serotonin into N-acetylserotonin. Using a quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) assay with internal standards,
      and an in-situ RT-PCR hybridization assay we found evidence for the expression of
      AANAT in the rat brain. In the localization studies, the most prominent AANAT
      mRNA signal was found in the granule neurons of the hippocampus, the olfactory
      bulb, and the cerebellum, and in the gray matter of the spinal cord. Diurnal
      differences in AANAT mRNA content were observed in the pineal gland but not in
      the hippocampus; the content of AANAT mRNA was lower both in the pineal gland and
      the hippocampus of old (24 months) compared with young (2 months) rats. These
      data are consistent with the hypothesis that AANAT may play a physiological role
      in mammalian central nervous system neurons. Further studies are warranted into
      the possible functional significance of neuronal expression of AANAT mRNA.

PMID- 11985884
TI  - Lack of antiandrogenic effects in adult male rats following acute exposure to 2,2
      bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE).
AB  - Although the insecticide dichlorodiphenyltrichloroethane (DDT) was banned in the
      US in 1972, DDT and its major metabolite 2,2-bis(4-chlorophenyl)-1,1
      dichloroethylene (DDE) are still persistent in the environment. DDE at high doses
      is antiandrogenic in fetal and adult rats and, therefore, is of concern in humans
      exposed environmentally. The objective of this work was to determine the dose
      response relationship between DDE and its antiandrogenic effect in adult, male
      rats and to quantitate the concentration of DDE in tissues following oral
      exposures. Adult, male, Long-Evans rats (11-13 weeks) were castrated, implanted
      with testosterone capsules, and dosed by oral gavage with 0, 5, 12.5, 25, 50, or
      100 mg DDE per kg body weight (BW) per day in corn oil for 4 days. On day 5 the
      rats were euthanized and liver, adrenals, ventral prostate, and seminal vesicles
      were weighed as a measure of response to DDE exposure. Blood, adrenals, brain,
      fat, kidney, lung, liver, muscle, ventral prostate, seminal vesicles, and skin
      were analyzed for DDE concentrations. Testosterone and dihydrotestosterone were
      measured in serum. There was a decrease in prostate weight that was not dose
      dependent; only the prostate weights in rats treated with 12.5 mg DDE per kg BW
      per day were reduced significantly compared to controls. The liver displayed a
      dose-dependent increase in weight that was significantly greater than control at
      DDE doses of 25, 50, and 100 mg/kg BW per day. Blood concentrations of DDE ranged
      from 0.32 to 11.3 ppm, while tissue concentrations ranged from 0.72 to 2620 ppm
      with the highest concentration in fat. Although DDE concentrations in the
      androgen-responsive tissues were higher than concentrations previously shown in
      vitro to inhibit androgen-receptor transcriptional activity, these concentrations
      did not appear to be antiandrogenic in vivo. The doses administered to the rats
      in this study are at least 10(5)-fold greater than the daily, average of human
      dietary intake of DDE.

PMID- 11985885
TI  - Biochemical changes in primary culture of skeletal muscle cells following
      dimethoate exposure.
AB  - In order to investigate the cellular mechanism of muscular weakness in the
      Intermediate Myasthenia Syndrome (IMS) following acute organophosphate poisoning,
      we studied the cytotoxicity of dimethoate and its effects on the activity of
      acetylcholine esterase (AChE), Na+-K+-ATPase, succinate dehydrogenase (SDH), and
      Ca2+-ATPase in primary cultured skeletal muscle cells. The results showed that
      the activity of AChE was significantly inhibited in a dose and time-dependent
      manner when cells were exposed to dimethoate for 2 h, but the expression of heat
      shock protein (HSP70) in muscle cells was significantly increased in a time
      dependent manner following dimethoate exposure. Dimethoate can significantly
      increase the activity of Na+-K+-ATPase in the mitochondrial and cytoplasm
      fraction of muscle cells, and inhibit the activity of Ca2+-ATPase. This study
      suggests that the disruption of intracellular homeostasis and energy metabolism
      of the muscle cells may play a role in the etiology of IMS.

PMID- 11985886
TI  - Does prolonged oral exposure to cyanide promote hepatotoxicity and
      nephrotoxicity?
AB  - Long-term exposure to cyanide and/or its main metabolite, thiocyanate, has been
      associated with goiter, pancreatic diabetes and several neurological disorders.
      However, very little is found in the literature relating the nephrotoxic and
      hepatotoxic effects of these substances. Thus, the objective of the present study
      was to verify the effects of prolonged exposure to potassium cyanide (KCN) in
      these organs. Forty-six male adults rats, weighing approximately 200 g at the
      beginning of the experiment, were distributed into five groups-four experimental
      and one control. Experimental groups were dosed with target doses of 0.3, 0.9,
      3.0 or 9.0 mg KCN/kg per day, in the drinking water, during 15 days and the
      control groups received only tap water. At the end of this experiment, all rats
      were subjected to euthanasia and plasma samples were obtained in order to
      determine thiocyanate and thyroidal hormones levels and fragments of thyroid,
      kidney and liver were collected. Rats treated with the highest cyanide dose (9.0
      mg KCN/kg per day) showed lower body weight gain. An increase in the thiocyanate
      levels was verified in all experimental groups. The histopathologic study
      revealed hydropic degeneration of the renal tubular epithelial cells in those
      animals, which received KCN at the dose of 3.0-9.0 mg/kg per day. This study also
      showed hydropic degeneration of the hepatocytes of those animals, which received
      KCN at a dose of 9.0 mg/kg per day, and in the thyroid gland an increase was
      observed in the number of reabsorption vacuoles on follicular colloid, in a dose
      dependent manner, in all animals of the experimental groups.

PMID- 11985887
TI  - Comparison of antiandrogenic activities of vinclozolin and D,L-camphorquinone in
      androgen receptor gene transcription assay in vitro and mouse in utero exposure
      assay in vivo.
AB  - A chemical substance used as a photoinitiator for light-cure resin compositions,
      D,L-camphorquinone (CQN) was found to be weakly antiandrogenic in vitro. It
      competitively antagonized dihydrotestosterone (DHT)-induced transcriptional
      activity on the yeast-based androgen receptor gene transcription assay (YAA).
      Antiandrogenic activity of CQN was shown at higher concentration than 10(-4) M
      while the well-known antiandrogen, vinclozolin (VCZ) showed the activity at
      concentrations of 10(-6) M and above in YAA. The antiandrogenic activity of CQN
      was reconfirmed in the human cell line-based androgen receptor gene transcription
      assay (HCAA). To determine whether CQN affect male reproductive development, CQN
      or VCZ was administered to pregnant mice daily from gestational days 10 to 18 by
      gavage. In utero exposure to VCZ at 100 mg/kg/day caused a significant decrease
      in anogenital distance (AGD) of F1 neonates and reduced spermatogenesis in F1
      males at 42 days of age. In contrast, maternal doses (100 and 300 mg/kg/day) of
      CQN had no affect on these endpoints in F1 offspring. Further, VCZ or CQN had no
      adverse affect on F1 male fertility. From these observations, CQN is potentially
      antagonistic to androgen receptor (AR) in vitro, but is estimated to be less
      antiandrogenic in vivo when it is administered to pregnant mice by gavage.
      Furthermore, these findings are the first to demonstrate that VCZ exerts
      significant antiandrogenic effects on reproductive tract development during
      gestation in mice.

PMID- 11985888
TI  - Upregulation of stress response mRNAs in COS-7 cells exposed to cadmium.
AB  - Exposure of cells to cadmium (Cd) is known to stimulate the expression of various
      types of genes. These changes in gene expression are presumed to be related to
      the cellular response to Cd toxicity. To better understand the mechanisms related
      to Cd toxicity, suppression subtractive hybridization was carried out on COS-7
      cells (African green monkey kidney cells) and the gene expression induced by Cd
      exposure was investigated. Heat shock protein (hsp) 10, 40, 60, 70, 89alpha and
      metallothionein II (MTII) mRNAs were found to be induced by Cd. This is the first
      report to describe the Cd-inducibility of hsp10, 40 and 89alpha mRNAs. Semi
      quantitative reverse-transcription polymerase chain reaction showed the diverse
      expression patterns of these genes, depending on Cd concentration and exposure
      time. A marked elevation of hsp70 mRNA and induction of mRNA for the co
      chaperone, hsp40, were detected. A relatively low level of hsp10 and hsp60 mRNAs
      was induced, with only a 2-fold increase within 24 h. Hsp89alpha mRNA was induced
      shortly after Cd exposure. These various induction patterns suggest that hsps
      play different roles in the cell against Cd toxicity.

PMID- 11985889
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on preimplantation mouse
      embryos.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental contaminant
      that can exert developmental toxicity. To investigate the stage-specific effects
      of TCDD on preimplantation embryos, we exposed mouse embryos to TCDD at different
      stages (1-, 2-, and 8-cell) and collected them at different stages of development
      (the 1- or 2-, 8-cell, and blastocyst stage, respectively). Semiquantitative RT
      PCR revealed increased constitutive gene expression of the arylhydrocarbon
      receptor (AhR) and AhR nuclear translocator (Arnt) at the 1-cell stage, decreased
      expression at the 2- to 8-cell stage, and increased expression again at the
      blastocyst stage, and addition of TCDD to media did not affect their mRNA levels.
      Interestingly, no cytochrome P4501A1 (CYP1A1) mRNA was detected in embryos at the
      1-, 2-, and 8-cell stages after exposure to 10 nM TCDD for 12 or 24 h, whereas
      CYP1A1 mRNA was significantly increased at the blastocyst stage in response to
      TCDD, and its induction was found to be concentration-dependent on TCDD exposure
      from 0.01 to 10 nM for 24 h. In addition, no significant differences in
      development rate of preimplantation embryos, cell number of blastocyst embryos,
      or apoptotic indices, such as TUNEL-positive cell number or Bax/Bcl-2 expression
      ratios were observed at the blastocyst stage between TCDD-exposed groups and non
      exposed group. These results suggest that the sensitivity to TCDD differs with
      the embryonic stage, which may reflect an ability of embryos to adapt to
      environmental stressors, such as dioxins.

PMID- 11985890
TI  - Effect of some hypoglycemic herbs on the activity of phase I and II drug
      metabolizing enzymes in alloxan-induced diabetic rats.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and N-nitrosamines (NNA) are mainly
      activated by cytochrome P450s, and their associated enzyme activities such as
      aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH), N-nitrosdimethylamine N
      demethylase I (NDMA-dI), NADPH-cytochrome C reductase, and detoxified by
      glutathione S-transferase (GST) and glutathione (GSH). The present study shows
      the influence of Cymbopogon proximus (Halfa barr), Zygophyllum coccineum L.
      (Kammun quaramany), Lupinus albus (Termis) as herbs capable of inducing
      hypoglycemia on the activity of the above mentioned enzymes in the liver of
      diabetic rats. Alloxan was administered as a single dose (120 mg/kg body weight)
      to induce diabetes and the herbs were administered to diabetic rats as repeated
      doses for 4 weeks. Alloxan-induced diabetes significantly increased the blood
      glucose level by 93% compared to the control level. On the other hand, repeated
      dose treatments of diabetic rats with Cymbopogon proximus and Lupinus albus are
      more effective than Zygophyllum coccineum in restoring the elevated blood glucose
      level to the normal level. Alloxan treatment increased the hepatic activity of
      cytochrome P450, NADPH-cytochrome C reductase, AHH, NDMA-dI, GST and GSH by 112,
      122, 82, 99, 64 and 26%, respectively. These herbs decreased the activity of
      above mentioned enzymes in the liver of diabetic rats compared to alloxan-treated
      rats. We conclude that alloxan increased the activity of cytochrome P450 system
      and that such herbs reduced these activities. The toxic effects of PAHs (e.g.
      benzo(a)pyrene) and NNA (e.g. N-nitrosdimethylamine) could be increased in the
      liver of diabetic rats through induction of their corresponding bioactivating
      enzymes. On the other hand, hypoglycemic herbs could alleviate the deleterious
      effects of these carcinogens in the liver of diabetic rats since these herbs
      reduced the hepatic content of cytochrome P450 and other associated enzyme
      activities compared to the diabetic group. Such alterations in the activity of
      phase I and II drug-metabolizing enzymes should be considered when therapeutic
      drugs are administered to diabetic patients since most of drugs are metabolized
      mainly by the cytochrome P450 system.

PMID- 11985891
TI  - Reduction of streptavidin RYDS-mediated renal adhesion by site-directed
      mutagenesis.
AB  - Naturally occurring core-Streptavidin (c-Strep) would serve as a more useful
      agent in vivo if not for its high kidney retention. This retention is mediated by
      an integrin-binding motif-RYDS-that shares homology to the more common RGDS. We
      generated a c-Strep molecule constituting amino acids 13-139 of streptavidin and
      by site-directed mutagenesis altered the RYDS motif to RYES. RYDS-c-Streptavidin
      and RYES-c-Streptavidin were expressed in E. coli and purified on a 2
      imminobiotin matrix. Each demonstrated an affinity for biotin similar to that of
      native post-secretory streptavidin while maintaining their ability to form dimers
      and tetramers. The mutant RYES-c-Streptavidin was no longer able to mediate
      normal rat kidney cell attachment in an in vitro assay. RYDS-c-Streptavidin
      mediated kidney cell attachment was inhibited by competition with c-Streptavidin,
      RYDS-c-Streptavidin and RGDS-containing peptides but not with an irrelevant
      peptide or RYES-c-Streptavidin. Therefore, the point mutation D49E generates a
      molecule, which may not display the in vivo kidney retention observed for RYDS-c
      Streptavidin, potentially finding more widespread clinical application.

PMID- 11985892
TI  - Protective effects of carnosine, homocarnosine and anserine against peroxyl
      radical-mediated Cu,Zn-superoxide dismutase modification.
AB  - Carnosine (beta-alanyl-L-histidine), homocarnosine (gamma-amino-butyryl-L
      histidine) and anserine (beta-alanyl-1-methyl-L-histidine) have been proposed to
      act as anti-oxidants in vivo. The protective effects of carnosine and related
      compounds against the oxidative damage of human Cu,Zn-superoxide dismutase (SOD)
      by peroxyl radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride
      (AAPH) were studied. The oxidative damage to Cu,Zn-SOD by AAPH-derived radicals
      led to protein fragmentation, which is associated with the inactivation of
      enzyme. Carnosine, homocarnosine and anserine significantly inhibited the
      fragmentation and inactivation of Cu,Zn-SOD by AAPH. All three compounds also
      inhibited the release of copper ions from the enzyme and the formation of
      carbonyl compounds in AAPH-treated Cu,Zn-SOD. These compounds inhibited the
      fragmentation of other protein without copper ion. The results suggest that
      carnosine and related compounds act as the copper chelator and peroxyl radical
      scavenger to protect the protein fragmentation. Oxidation of amino acid residues
      in Cu,Zn-SOD induced by AAPH were significantly inhibited by carnosine and
      related compounds. It is proposed that carnosine and related dipeptides might be
      explored as potential therapeutic agents for pathologies that involve Cu,Zn-SOD
      modification mediated by peroxyl radicals.

PMID- 11985893
TI  - Antioxidative or prooxidative effect of 4-hydroxyquinoline derivatives on free
      radical-initiated hemolysis of erythrocytes is due to its distributive status.
AB  - 7-Chloro-4-hydroxyquinoline (CQ) is an antitumor drug but its efficiency is not
      very satisfactory. This fact motivates us to study the relationship between the
      structure of 4-hydroxyquinoline with various substituent and its antioxidant
      effect against free-radical-initiated peroxidation: the hemolysis of human
      erythrocyte initiated thermally by water-soluble initiator, 2,2'-azobis (2
      amidinopropane hydrochloride) (AAPH), acts as an experimental system. 7-Fluoro-4
      hydroxyquinoline (FQ) and CQ can be synthesized by decarboxylation of 7-fluoro-4
      hydroxyquinoline-3-carboxylic acid (FQCA) and 7-chloro-4-hydroxyquinoline-3
      carboxylic acid (CQCA), respectively, and FQCA and CQCA are prepared by
      hydrolysis of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (FQCE) and ethyl 7
      chloro-4-hydroxyquinoline-3-carboxylate (CQCE), respectively. The inhibitory
      concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the
      erythrocyte has been studied and found that all these chemicals dissolved in
      dimethyl sulfoxide (DMSO) can inhibit the free-radical-induced peroxidation. To
      clarify the relationship between the distributive status of the chemicals and
      their antioxidant effect, the chemical has been dissolved in the vesicle of
      dipalmitoyl phosphatidylcholine (DPPC) by sonication and suspended in the
      reaction system. It is found that FQCE, CQCE, FQCA and CQCA act as prooxidants
      either used alone or used in combination with alpha-tocopherol (TOH),
      demonstrating that FQCE, CQCE, FQCA and CQCA play a prooxidative role when they
      are packaged in the DPPC vesicle. This can be understood that the electron
      attracting group, i.e. -COOC(2)H(5), -COOH, at the ortho position to the hydroxy
      group of quinoline makes the phenoxy radical of quinoline derivatives active by
      attracting negative charge from the electron-deficient radical site. These
      unstable free radicals preserved in DPPC vesicle can initiate additional
      propagation of lipid peroxidation and cause hemolysis. However, FQ and CQ without
      electron-attracting group are antioxidants even in DPPC vesicle either used
      alone, or mixed with TOH. Moreover, the antioxidative activity of FQ is much
      better than CQ either used alone or in combination with TOH, indicating that FQ
      has the potential to replace CQ to be an antioxidant drug. Therefore, the
      antioxidant/prooxidant effect is not only correlated with the molecular structure
      but also the distributive status in the reaction system.

PMID- 11985894
TI  - Time-resolved 1H and 13C NMR spectroscopy for detailed analyses of the
      Azotobacter vinelandii mannuronan C-5 epimerase reaction.
AB  - AlgE2, AlgE4, and AlgE6 are members of a family of mannuronan C-5 epimerases
      encoded by Azotobacter vinelandii, and are active in the biosynthesis of
      alginate, where they catalyze the post-polymerization conversion of beta-D
      mannuronic acid residues into alpha-L-guluronic acid residues. To study the
      kinetics and mode of action of these enzymes, homopolymeric mannuronan and other
      alginate samples with various composition were epimerized by letting the
      enzymatic reaction take place in an NMR tube. Series of 1H NMR spectra were
      recorded to obtain a time-resolved picture of the epimerization progress and the
      formation of specific monomer sequences. Starting from mannuronan, guluronic acid
      contents of up to 82% were introduced by the enzymes, and the product
      specificity, substrate selectivity, and reaction rates have been investigated. To
      obtain direct information of the GulA-block formation, similar experiments were
      performed using a 13C-1-enriched mannuronan as substrate. The NMR results were
      found to be in good agreement with data obtained by a radioisotope assay based on
      3H-5-labeled substrates.

PMID- 11985895
TI  - Channel modulators affect PGE(2) binding to bovine aortic endothelial cells.
AB  - PGE(2), PGF(2alpha) and the thromboxane agonist U-46619 bind to bovine aortic
      endothelial cells and compete on the same binding site with similar affinity. In
      addition, binding remains unaffected by prolonged exposure to the ligand. These
      characteristics differ significantly from those of any known G-coupled
      prostaglandin receptor. Binding of PGE(2) to the cells is reduced in the presence
      of the cyclic nucleotides cGMP and cAMP, and is unaffected by protein kinase
      inhibitors. Removal of permeable cyclic nucleotides from the cell medium results
      in a fast and complete restoration of PGE(2) binding to the cells, suggesting
      that both cyclic nucleotides reduce PGE(2) binding by a reversible interaction
      with the prostaglandin-binding site, without the involvement of second messenger
      activated protein kinases. Our data further show that binding of prostaglandins
      to bovine aortic endothelial cells is sensitive to heavy metals and to activators
      and blockers of calcium, ATP-sensitive K(+) and chloride channels. Nickel, a
      specific cyclic nucleotide-gated (CNG) channel activator, decreases PGE(2)
      binding and so do the CNG channel activators Rp-8-Br-PET-cGMPS and Sp-8-Br-PET
      cGMPS. On the other hand, the calcium channel blockers pimozide, diltiazem as
      well as LY-83,583, a guanylate cyclase inhibitor, which were reported to block
      CNG channels, enhance PGE(2) binding. The sensitivity of PGE(2) binding to
      selective CNG channel modifying agents, as well as the rapid and reversible
      interaction with cyclic nucleotides, may suggest that the common low-affinity
      prostanoid-binding site on bovine aortic endothelial cells is associated with a
      molecular entity, which possess several properties of a CNG channel.

PMID- 11985896
TI  - A calpain-like activity insensitive to calpastatin in Drosophila melanogaster.
AB  - Calpains are neutral Ca2+-dependent cysteine proteases. In this study, we
      utilized casein zymography to detect such a proteolytic activity in Drosophila
      melanogaster extracts throughout the life of this organism. One calpain-like
      activity that was sensitive to the general cysteine protease inhibitors, E64 and
      calpain inhibitor I, but insensitive to the human calpain-specific inhibitor,
      calpastatin, is demonstrated. The relevance of this finding is discussed with
      respect to the absence of a corresponding Drosophila gene, homologous to the
      vertebrate calpastatin genes, as concluded from our unsuccessful attempts to
      clone such a gene and our Blast searches using the FlyBase. The mechanisms of
      Drosophila calpain regulation require further investigation. However, we suggest
      that single chain, non-heterodimeric calpains may be insensitive to calpastatin
      and that Drosophila cystatin-like molecules may play a role in negatively
      regulating Drosophila calpain.

PMID- 11985897
TI  - Effect of nitrosylmyoglobin and saturated fatty acid anions on metmyoglobin
      catalyzed oxidation of aqueous methyl linoleate emulsions.
AB  - In aqueous methyl linoleate emulsions (pH 7.4, 25 degrees C, air-saturated),
      nitrosylmyoglobin and saturated fatty acid anions (palmitate and stearate
      investigated) each showed antioxidant effect on metmyoglobin-induced peroxidation
      as measured by oxygen depletion rate. For equimolar concentration of
      nitrosylmyoglobin and metmyoglobin and for metmyoglobin in moderate excess, a
      reduction in oxygen consumption rate of approximately 70% was observed. Fatty
      acid anions reduced oxygen consumption rate most significantly for palmitate (up
      to 60% for a fatty acid:heme protein ratio of 90:1). No further antioxidative
      effect was seen for fatty acid anions in the presence of nitrosylmyoglobin,
      whereas nitrosylmyoglobin showed a further antioxidant effect in presence of
      fatty acid anions in the metmyoglobin-catalyzed process. The antioxidative
      mechanism of nitrosylmyoglobin and fatty acid anions is different, and while the
      fatty acid anions seem active in inhibiting initiation of oxidation through
      protection against metmyoglobin activation into perferrylmyoglobin, as shown by
      freeze-quench Electron Spin Resonance (ESR) spectroscopy, nitrosylmyoglobin is
      rather active in the oxygen consuming (propagation) phase.

PMID- 11985898
TI  - Ethanol perfusion increases the yield of oxidative phosphorylation in isolated
      liver of fed rats.
AB  - The question arises as to the effect of ethanol on the actual yield of oxidative
      phosphorylation in the whole liver because of contradictory results reported in
      isolated hepatic mitochondria. The adenosine triphosphate (ATP) content of liver
      isolated from fed rats and perfused in the presence (10 mM) and absence of
      ethanol was continuously evaluated using 31P Nuclear Magnetic Resonance (NMR). An
      accurate estimation of mitochondrial ATP synthesis in the whole organ was
      obtained by subtracting the glycolytic ATP supply from the total ATP production.
      Simultaneously, the respiratory activity was assessed using O(2) Clark
      electrodes. The data indicate that ethanol enhanced the net consumption of ATP,
      leading to a new steady state of the ATP content. ATP synthesis was also found
      higher under ethanol [1.86+/-0.02 micromol/min g wet weight (min g ww)] than in
      control [1.44+/-0.18 micromol/min g ww]. However, mitochondrial respiration
      remained unchanged [2.20+/-0.13 micromol/min g ww] and, consequently, the in situ
      mitochondrial ATP/O ratio increased from 0.33+/-0.035 (control) to 0.42+/-0.015
      (ethanol). The increase of the oxidative phosphorylation yield in the whole liver
      may be linked to the decrease in cytochrome oxidase activity induced by ethanol
      [FEBS Lett. 468 (2000) 239]. The significant raise (27%) of the ATP/O ratio was
      not sufficient to maintain the ATP level following ethanol-increased ATP
      consumption.

PMID- 11985899
TI  - Functional investigation of a gene encoding pteridine glycosyltransferase for
      cyanopterin synthesis in Synechocystis sp. PCC 6803.
AB  - A gene (slr1166) putatively encoding pteridine glycosyltransferase was disrupted
      with a kanamycin resistance cassette in Synechocystis sp. PCC 6803, which
      produces cyanopterin. The deduced polypeptide from slr1166 consisted of 354 amino
      acid residues sharing 45% sequence identity with UDP-glucose:tetrahydrobiopterin
      alpha-glucosyltransferase (BGluT) isolated previously from Synechococcus sp. PCC
      7942. The knockout mutant was unable to produce cyanopterin but only 6
      hydroxymethylpterin-beta-galactoside, verifying that slr1166 encodes a pteridine
      glycosyltransferase, which is responsible for transfer of the second sugar
      glucuronic acid in cyanopterin synthesis. The mutant was affected in its
      intracellular pteridine content and growth rate, which were 74% and 80%,
      respectively, of wild type, demonstrating that the second sugar residue is still
      required for quantitative maintenance of cyanopterin. This supports the previous
      suggestion that glycosylation may contribute to high cellular concentration of
      pteridine compounds.

PMID- 11985900
TI  - Citizens of the world.

PMID- 11985901
TI  - Surrogate end points in heart failure.
AB  - Because of the increasing number of pharmacologic strategies available for
      treatment of heart failure (HF), the time has come to reassess the adequacy of
      end points used to evaluate therapeutic efficacy. Interest in the use of
      surrogate end points in clinical studies is increasing. A surrogate end point is
      defined as a measurement that can substitute for a true end point for the purpose
      of comparing specific interventions or treatments in a clinical trial. A true end
      point is one that is of clinical importance to the patient (e.g., mortality or
      quality of life), whereas a surrogate end point is one biologically closer to the
      disease process (e.g., ejection fraction or left ventricular volume in HF). The
      prime motivation for the use of a surrogate end point concerns the possible
      reduction in sample size or trial duration. Such reductions have important cost
      implications and in some cases may influence trial feasibility. Another, perhaps
      more important, aspect of measuring surrogate end points is that they increase
      our understanding of the mechanism of action of drugs and thus may help
      physicians to take a more enlightened approach in managing their patients. In
      this article we have analyzed the possible potentials of the surrogate end points
      in clinical studies of patients with chronic HF. Other uses of possible
      surrogates are discussed, and the limitations in finding true surrogates are
      mentioned. At this time we conclude there is no well established surrogate in HF.

PMID- 11985902
TI  - N-acetylcysteine in acute cardiology: 10 years later: what do we know and what
      would we like to know?!
AB  - N-acetylcysteine (NAC) is known in a variety of branches of medicine. This paper
      addresses in detail the action of NAC as it is emerging from research and
      clinical trials over the past decade in cardiology, giving rise to new concepts.
      The result is a process resembling creation of a mosaic from individual pieces.
      Also, the role of NAC in acute cardiology, during acute reperfusion in
      particular, is defined.

PMID- 11985903
TI  - Identification, regulation and function of a novel lectin-like oxidized low
      density lipoprotein receptor.
AB  - Oxidatively modified low-density lipoprotein (ox-LDL) leads to endothelial
      activation, dysfunction and injury. Recently, a novel lectin-like receptor for ox
      LDL (LOX-1) has been identified, primarily in the endothelial cells, and it
      allows uptake of ox-LDL into endothelial cells. This receptor is
      transcriptionally upregulated by tumor necrosis factor-alpha, angiotensin II,
      shear stress and ox-LDL itself. The expression of this receptor activates a
      variety of intracellular processes that lead to expression of adhesion molecules
      and endothelial activation. This receptor is highly expressed in the blood
      vessels of animals and humans with hypertension, diabetes mellitus and
      atherosclerosis. Expression of this receptor may also be relevant in intra
      arterial thrombogenesis and myocardial ischemia-reperfusion injury.
      Identification and regulation of this receptor and understanding of signal
      transduction pathways may lead to new therapies of diseases characterized by
      endothelial dysfunction.

PMID- 11985904
TI  - Embolic events in patients with atrial fibrillation and effective
      anticoagulation: value of transesophageal echocardiography to guide direct
      current cardioversion. Final results of the Ludwigshafen Observational
      Cardioversion Study.
AB  - OBJECTIVES: The primary objective was to evaluate the usefulness of
      transesophageal echocardiography (TEE)-guided cardioversion to prevent
      thromboembolic complications in patients with atrial fibrillation (AF) and
      effective anticoagulation (International Normalized Ratio of 2 or 3) at least
      three weeks before cardioversion. BACKGROUND: Transesophageal echocardiography
      has been proposed as a method of screening patients for left atrial thrombi
      before direct-current cardioversion of AF. The usefulness of TEE as a screening
      tool has always been evaluated in patients without long-term anticoagulation
      before cardioversion. METHODS: This prospective, single-center, observational
      study, performed on an intention-to-cardiovert basis, comprised 1,076
      consecutive, unselected patients with AF. The initial two years were designed to
      be the control phase, during which the conventional approach was used. After
      that, cardioversion guided by TEE was performed in consecutive patients. RESULTS:
      The prevalence of left atrial thrombi was 7.7% in patients with persistent AF and
      effective anticoagulation. During the first four weeks after electrical
      cardioversion, six thromboembolic complications were observed in patients in whom
      the TEE-guided approach was employed (6 [0.8%] of 719 patients), compared with
      three thromboembolic complications in patients in whom the conventional approach
      was used (3 [0.8%] of 357 patients). None of the patients in whom electrical
      cardioversion was not performed experienced an embolic event. CONCLUSIONS: There
      were no differences in the rate of embolic events between the two treatment
      groups. In patients with AF and effective anticoagulation, TEE-guided electrical
      cardioversion does not reduce the embolic risk. However, TEE revealed left atrial
      thrombi in 7.7% of patients with AF and effective anticoagulation, before direct
      current cardioversion.

PMID- 11985905
TI  - Clinical value of left atrial appendage flow for prediction of long-term sinus
      rhythm maintenance in patients with nonvalvular atrial fibrillation.
AB  - OBJECTIVES: This study evaluated the role of various clinical and
      echocardiographic parameters, including the left atrial appendage (LAA)
      anterograde flow velocity, for prediction of the long-term preservation of sinus
      rhythm (SR) in patients with successful cardioversion (CV) of nonvalvular atrial
      fibrillation (AF). BACKGROUND: Echocardiographic parameters for assessing long
      term SR maintenance after successful CV of nonvalvular AF are not accurately
      defined. METHODS: Clinical, transthoracic echocardiographic and transesophageal
      echocardiographic (TEE) data--measured in AF lasting >48 h--of 186 consecutive
      patients (116 men, mean age: 65 +/- 9 years) with successful CV (electrical or
      pharmacologic) were analyzed for assessment of one-year maintenance of SR.
      RESULTS: At one-year follow-up, 91 of 186 (49%) patients who underwent successful
      CV continued to have SR. Mean LAA peak emptying flow velocity was higher in
      patients remaining in SR for one year than in those with AF relapse (41.7 +/-
      20.2 cm/s vs. 27.7 +/- 17.0 cm/s; p < 0.001). On multivariate logistic regression
      analysis, only the mean LAA peak emptying velocity >40 cm/s (p = 0.0001; chi(2):
      23.9, odds ratio [OR] = 5.2, confidence interval [CI] 95% = 2.7 to 10.1) and the
      use of preventive antiarrhythmic drug treatment (p = 0.0398; chi(2): 4.2; OR =
      2.0, CI 95% = 1.0 to 3.8) predicted the continuous preservation of SR during one
      year, outperforming other univariate predictors such as absence of left atrial
      spontaneous echocardiographic contrast during TEE, the left atrial parasternal
      diameter <44 mm, left ventricular ejection fraction >46% and AF duration <1 week
      before CV. The negative and positive predictive values of the mean LAA peak
      emptying velocity >40 cm/s for assessing preservation of SR were 66% (CI 95% =
      56.9 to 74.2) and 73% (CI 95% = 62.4 to 83.3), respectively. CONCLUSIONS: In TEE
      guided management of nonvalvular AF, high LAA flow velocity identifies patients
      with greater likelihood to remain in SR for one year after successful CV. Low LAA
      velocity is of limited value in identifying patients who will relapse into AF.

PMID- 11985906
TI  - Right ventricular dysfunction and risk of heart failure and mortality after
      myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to determine the prognostic value of right
      ventricular (RV) function in patients after a myocardial infarction (MI).
      BACKGROUND: Right ventricular function has been shown to predict exercise
      capacity, autonomic imbalance and survival in patients with advanced heart
      failure (HF). METHODS: Two-dimensional echocardiograms were obtained in 416
      patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] < or =
      40%) from the Survival And Ventricular Enlargement (SAVE) echocardiographic
      substudy (mean 11.1 +/- 3.2 days post infarction). Right ventricular function
      from the apical four-chamber view, assessed as the percent change in the cavity
      area from end diastole to end systole (fractional area change [FAC]), was related
      to clinical outcome. RESULTS: Right ventricular function correlated only weakly
      with the LVEF (r = 0.12, p = 0.013). On univariate analyses, the RV FAC was a
      predictor of mortality, cardiovascular mortality and HF (p < 0.0001 for all) but
      not recurrent MI. After adjusting for age, gender, diabetes mellitus,
      hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment
      assignment, RV function remained an independent predictor of total mortality,
      cardiovascular mortality and HF. Each 5% decrease in the RV FAC was associated
      with a 16% increased odds of cardiovascular mortality (95% confidence interval
      4.3% to 29.2%; p = 0.006). CONCLUSIONS: Right ventricular function is an
      independent predictor of death and the development of HF in patients with LV
      dysfunction after MI.

PMID- 11985907
TI  - Revisiting the culprit lesion in non-Q-wave myocardial infarction. Results from
      the VANQWISH trial angiographic core laboratory.
AB  - OBJECTIVE: We sought to determine the underlying coronary anatomy and
      characterize the culprit lesion after non-Q-wave myocardial infarction (NQWMI).
      BACKGROUND: Although the culprit lesion and infarct-related artery often are
      easily identified with coronary angiography after Q-wave MI, the culprit lesion
      after NQWMI has not been well characterized. Small retrospective studies have
      suggested that the absence of Q-waves on an electrocardiogram is due to
      incomplete occlusion of the infarct-related artery. METHODS: Coronary angiograms
      from 350 patients randomized to the early invasive strategy in the Veterans
      Affairs Non-Q-Wave Infarction Strategies in-Hospital (VANQWISH) trial were
      systematically analyzed in an angiographic core laboratory. A consensus panel
      identified the culprit lesion and the infarct-related artery using prespecified
      criteria for complex lesion morphology and acute versus chronic occlusions.
      Severity of angiographic disease and left ventricular function also were
      analyzed. Patients with a single identified culprit lesion were compared with
      those who had multiple apparent culprits and those without an identifiable
      culprit lesion. RESULTS: A single culprit lesion was identified in only 49% of
      patients undergoing early angiography after NQWMI. The majority of patients
      either had no identifiable culprit (37%) or multiple apparent culprit lesions
      (14%). A single incomplete occlusion of the infarct-related artery was found in
      only 36% of patients, and an isolated acute occlusion of the infarct-related
      artery occurred in 13%. Patients without an identifiable culprit lesion had
      severe coronary disease (obstructive coronary artery disease [CAD] in 84%) but no
      complex lesion morphology. There was no difference in angiographic severity of
      disease comparing patients with and without identifiable culprit lesions.
      Patients with a single incomplete occlusion of the infarct-related artery were
      more likely to undergo percutaneous transluminal coronary angioplasty than other
      patients, whereas patients with multiple culprit lesions were more frequently
      treated with coronary artery bypass grafting. CONCLUSIONS: Coronary angiography
      early after NQWMI frequently identifies severe obstructive CAD, but a single
      identifiable culprit lesion was identified in <50% of patients. Multiple culprit
      lesions were seen in 14% of patients. An angiographic culprit lesion could not be
      identified in more than one-third of patients undergoing coronary angiography as
      part of an invasive strategy.

PMID- 11985908
TI  - Angiographic plaque complexity: the tip of the unstable plaque iceberg.

PMID- 11985909
TI  - Active interstitial remodeling: an important process in the hibernating human
      myocardium.
AB  - OBJECTIVES: The purpose of this study is to investigate the morphologic
      characteristics of the cardiac interstitium in the hibernating human myocardium
      and evaluate whether active remodeling is present and is an important determinant
      of functional recovery. BACKGROUND: Myocardial hibernation is associated with
      structural myocardial changes, which involve both the cardiomyocytes and the
      cardiac interstitium. METHODS: We evaluated 15 patients with coronary disease
      with two-dimensional echocardiography and thallium-201 ((201)Tl) tomography
      before coronary bypass surgery. During surgery, transmural myocardial biopsies
      were performed guided by transesophageal echocardiography. Myocardial biopsies
      were stained immunohistochemically to investigate fibroblast phenotype and
      examine evidence of active remodeling in the heart. RESULTS: Among the 29
      biopsied segments included in the study, 24 showed evidence of systolic
      dysfunction. The majority of dysfunctional segments (86.4%) were viable ((201)Tl
      uptake > or = 60%). After revascularization, 12 dysfunctional segments recovered
      function as assessed with an echocardiogram three months after bypass surgery.
      Interstitial fibroblasts expressing the embryonal isoform of smooth muscle myosin
      heavy chain (SMemb) were noted in dysfunctional segments, predominantly located
      in border areas adjacent to viable myocardial tissue. Segments with recovery had
      higher SMemb expression (0.46 +/- 0.16% [n = 12] vs. 0.10 +/- 0.02% [n = 12]; p <
      0.05) and a higher ratio of alpha-smooth muscle actin to collagen (0.14 +/- 0.026
      [n = 12] vs. 0.07 +/- 0.01 [n = 12]; p < 0.05) compared with segments without
      recovery, indicating fibroblast activation and higher cellularity of the fibrotic
      areas. In addition, interstitial deposition of the matricellular protein
      tenascin, a marker of active remodeling, was higher in hibernating segments than
      in segments with persistent dysfunction (p < 0.05), suggesting an active
      continuous fibrotic process. Multiple logistic regression demonstrated a
      significant independent association between SMemb expression and functional
      recovery (p < 0.01). CONCLUSIONS: Fibroblast activation and expression of SMemb
      and tenascin provide evidence of continuous remodeling in the cardiac
      interstitium of the hibernating myocardium, an important predictor of recovery of
      function after revascularization.

PMID- 11985910
TI  - Prognostic value of the Duke treadmill score in the elderly.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that the Duke
      treadmill score works less well for risk stratification in patients age 75 years
      or above. BACKGROUND: Although the Duke treadmill score is generally effective
      for risk stratification, its prognostic value in the elderly may be limited
      because they have a higher prevalence of coronary artery disease (CAD), more
      severe CAD and a lower exercise tolerance. METHODS: The study population
      consisted of 247 patients age 75 years or above, and the control population
      consisted of 2,304 patients below 75 years of age. All patients were symptomatic,
      had undergone exercise thallium testing between 1989 and 1991 and were followed
      for a median of >6.5 years. The Cox regression model was used to test the
      association of the Duke score (utilized both as a continuous variable and using
      previously published risk group cutoffs) with outcomes (cardiac death, nonfatal
      myocardial infarction [MI], late revascularization). RESULTS: Using the Duke
      score to risk-stratify the elderly, 26% were in the low risk group, 68% were in
      the intermediate risk group and 6% were in the high risk groups; seven-year
      cardiac survival was 86%, 85% and 69%, respectively (p = 0.45). There was also no
      significant association between these Duke score risk groups and all other
      outcome end points in the elderly. The Duke score as a continuous variable did
      not predict cardiac death (p = 0.43) or cardiac death or MI (p = 0.42), but did
      predict total cardiac events (which included late revascularization) (p =
      0.0027). For the control population, more patients (55%) were in the low risk
      group, and the Duke score (as a continuous variable or in risk groups) was highly
      predictive of all end points (p = 0.0001). CONCLUSIONS: The Duke score predicted
      cardiac survival in younger patients but not in patients age 75 years or above.
      The majority of the elderly were classified as intermediate risk by the Duke
      score. Only a minority of the elderly were classified as low risk, but this group
      still had an annual cardiac mortality of 2%/year.

PMID- 11985911
TI  - Physical activity attenuates the effect of increased left ventricular mass on the
      risk of ischemic stroke: The Northern Manhattan Stroke Study.
AB  - OBJECTIVES: The goal of this study was to determine whether the risk of ischemic
      stroke associated with increased left ventricular mass (LVM) is modified by
      physical activity (PA). BACKGROUND: Increased LVM is associated with an increased
      risk for stroke. Physical activity can decrease the risk of stroke and may have
      variable effects on LVM. METHODS: We used a case-control study design in a
      multiethnic population in northern Manhattan, New York, to study 394 case
      subjects who had a first ischemic stroke and 413 stroke-free control subjects.
      All subjects were interviewed and two-dimensional echocardiograms obtained to
      determine LVM. RESULTS: A sharp increase in risk of ischemic stroke was seen in
      the highest quartile of LVM (odds ratio [OR]: 6.14 [95% confidence interval [CI]:
      3.04 to 12.38]). Thus, increased LVM was defined by the highest quartile of LVM.
      In multivariate analysis, the effect of increased LVM on the risk of stroke was
      significantly decreased by the presence of any level of PA versus no PA (OR: 1.59
      [95% CI: 0.99 to 2.57] p < 0.07 vs. 3.53 [95% CI: 1.94 to 6.42] p < 0.0001).
      Although PA decreased the risk of stroke in all patients, the effect was stronger
      in subjects with increased LVM than among those without increased LVM (p =
      0.033). CONCLUSIONS: Increased LVM is associated with an increased risk of
      stroke, especially among sedentary patients. Physical activity decreases the risk
      of stroke among patients with increased LVM to a level comparable to that of
      patients without increased LVM. Recommending PA may be a nonpharmacologic tool to
      reduce the stroke risk, especially among patients with increased LVM.

PMID- 11985912
TI  - Risk of embolization after institution of antibiotic therapy for infective
      endocarditis.
AB  - OBJECTIVES: This study was designed to assess the risk of systemic embolization
      in patients with left-sided infective endocarditis, once adequate antibiotic
      treatment had been initiated, on the basis of prospective clinical follow-up.
      BACKGROUND: As one of the complications of infective endocarditis, embolization
      has a great impact on prognosis. Prediction of an individual patient's risk of
      embolization is very difficult. METHODS: We studied 217 episodes of left-sided
      endocarditis that were experienced among a cohort of 211 prospectively recruited
      patients. According to the Duke criteria, 91% of the episodes were definite
      infective endocarditis. Seventy-two episodes involved infections located on
      prosthetic valves. All patients were studied by transthoracic and transesophageal
      echocardiography. Clinical, echocardiographic and microbiologic data were entered
      in a data base. The mean follow-up interval was 151 days. RESULTS: Twenty-eight
      episodes (12.9%; group I) of endocarditis had embolic events after the initiation
      of antibiotic therapy. The remaining 189 episodes did not embolize (group II).
      Most emboli (52%) affected the central nervous system, and 65% of the embolic
      events occurred during the first two weeks after initiation of antibiotic
      therapy. Previous embolism was associated with new embolism (relative risk [RR]
      1.73, 95% confidence interval [CI] 1.02 to 2.93; p = 0.05). There was an increase
      in the risk of embolization with increasing vegetation size (RR 3.77, 95% CI 0.97
      to 12.57; p = 0.07). Vegetation size had no impact on the risk of embolization in
      streptococcal endocarditis or aortic infection. By contrast, large (> or = 10 mm)
      vegetations had a higher incidence of embolism when the microorganism was
      staphylococcus (p = 0.04) and the mitral valve was infected (p = 0.03). The
      increase in vegetation size at follow-up showed a higher risk for embolization
      (RR 2.64, 95% CI 0.98 to 7.16; p = 0.02). CONCLUSIONS: Embolism before
      antimicrobial therapy is a risk factor for new emboli. The risk of embolization
      seems to increase with increasing vegetation size, and this is particularly
      significant in mitral endocarditis and staphylococcal endocarditis. An increase
      in vegetation size, despite antimicrobial treatment, may predict later embolism.

PMID- 11985913
TI  - Effects of beraprost sodium, an oral prostacyclin analogue, in patients with
      pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled
      trial.
AB  - OBJECTIVES: The purpose of this study was to assess the efficacy and safety of
      beraprost sodium, an orally active prostacyclin analogue, in New York Heart
      Association (NYHA) functional class II and III patients with pulmonary arterial
      hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a life
      threatening disease for which continuous intravenous infusion of prostacyclin has
      been proven effective. However, this treatment is associated with serious
      complications arising from the complex delivery system. METHODS: In this double
      blind, placebo-controlled study, 130 patients with PAH were randomized to the
      maximal tolerated dose of beraprost (median dose 80 microg four times a day) or
      to placebo for 12 weeks. The primary end point was the change in exercise
      capacity assessed by the 6-min walk test. Secondary end points included changes
      in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class.
      RESULTS: Patients treated with beraprost improved exercise capacity and symptoms.
      The difference between treatment groups in the mean change of 6-min walking
      distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p =
      0.036). The difference in the mean change of Borg dyspnea index was -0.94 (95%
      CI: -1.63 to -0.24, p = 0.009). In the sub-group of patients with primary
      pulmonary hypertension, the difference in the mean change of 6-min walking
      distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary
      hemodynamics and NYHA functional class had no statistically significant changes.
      Drug-related adverse events were common in the titration phase and decreased in
      the maintenance period. CONCLUSIONS: Beraprost improves exercise capacity and
      symptoms in NYHA functional class II and III patients with PAH and, in
      particular, in those with primary pulmonary hypertension.

PMID- 11985914
TI  - Periodic rescreening is indicated for family members at risk of developing
      familial dilated cardiomyopathy.
AB  - OBJECTIVES: This study evaluated the role of clinical rescreening of family
      members at risk for familial dilated cardiomyopathy (FDC). BACKGROUND: Familial
      dilated cardiomyopathy is a genetic cardiomyopathy that usually is transmitted in
      an autosomal dominant pattern and may underlie from one-quarter to one-half of
      idiopathic dilated cardiomyopathy (IDC) diagnoses. Thus, FDC may present with
      advanced heart failure (HF) or sudden cardiac death (SCD). Because FDC may
      respond to medical intervention, we have previously recommended that screening of
      first-degree relatives (parents, siblings, children) of patients diagnosed with
      IDC be undertaken to rule out FDC, and that with a diagnosis of FDC in the
      kindred, unaffected but at-risk family members be rescreened every three to five
      years. METHODS; Follow-up screening (history, examination, electrocardiogram,
      echocardiography) of a large family with FDC was performed six years after
      initial screening. Of 68 family members who underwent rescreening, two (one with
      left ventricular enlargement only, one with a left bundle branch block) presented
      with advanced HF and SCD, respectively. Two additional subjects, asymptomatic at
      initial screening, were also affected with FDC at follow-up. CONCLUSIONS:
      Considerable vigilance for disease presentation and progression is indicated in
      at-risk members of a kindred with FDC, especially those with incipient FDC.

PMID- 11985915
TI  - The interleukin-6/interleukin-6-receptor system is activated in donor hearts.
AB  - OBJECTIVES: To assess the potential of the donor heart to respond to interleukin
      6 (IL6), the present study investigated the expression of IL6 receptor components
      in the myocardium of donor hearts before transplantation. BACKGROUND: Donor heart
      dysfunction early after transplantation has been associated with the cytokine
      storm after donor brain death. Proinflammatory cytokines are thought to play a
      central role in this process. Interleukin-6 is of specific interest because it
      has been associated with cardiac allograft dysfunction and is related to an
      impaired prognosis. Its action requires expression of the specific IL6 receptor
      (IL6R), and the common signal transducer of the IL6 family glycoprotein 130
      (gp130) in the donor heart. METHODS: The activation of IL6, IL6R and gp130
      messenger ribonucleic acid (mRNA) and protein was studied via reverse
      transcription-polymerase chain reaction (RT-PCR) and immunohistology in donor
      hearts (n = 6) and compared with patients undergoing evaluation of ventricular
      arrhythmias (control, n = 9) or with advanced heart failure (n = 20). RESULTS:
      Messenger RNA of IL6, IL6R and gp130 was strongly expressed in all chambers of
      donor hearts, whereas right ventricles of control patients did not show any
      expression (donor vs. control: p < 0.005). Right ventricles of failing hearts
      showed IL6, IL6R and gp130 mRNA levels comparable with those found in donor
      hearts. Immunohistochemistry paralleled the RT-PCR data on the protein level.
      While IL6 was mainly expressed by myocytes, both receptor components were
      preferentially found mainly on interstitial cells. CONCLUSIONS: The expression of
      the IL6 receptor components in the donor heart before transplantation establishes
      the condition sine qua non for the response of the donor heart to circulating
      IL6. This mechanism may explain the close association of elevated IL6 serum
      levels to acute cardiac allograft dysfunction in the early perioperative period.

PMID- 11985916
TI  - Coronary hemodynamics of stent implantation after suboptimal and optimal balloon
      angioplasty.
AB  - OBJECTIVES: This study was performed to evaluate hemodynamic alterations of stent
      implantation after Doppler flow-guided balloon angioplasty (BA). BACKGROUND:
      There is controversy regarding the effect of stent implantation on coronary
      hemodynamics after suboptimal and optimal BA. METHODS: A total of 523 of 620
      patients underwent Doppler-guided BA in the setting of a multicenter study and
      were analyzed before and after additional stent implantation. Balloon angioplasty
      was considered optimal when the diameter stenosis (DS) was < or = 35% and
      coronary flow reserve (CFR) was >2.5 and suboptimal if these two criteria were
      not met. Coronary flow reserve was also measured in an angiographically normal
      artery to determine relative CFR. Patients were followed for 12 months to
      document major adverse cardiac events (MACE). RESULTS: The main difference
      between patients with suboptimal BA (n = 195 [51%]) and optimal BA (n = 184
      [49%]) was a more pronounced increase in baseline blood flow velocity (15 +/- 8
      to 22 +/- 11 vs. 14 +/- 8 to 16 +/- 10 cm/s, p < 0.01). Coronary flow reserve
      improved after stent implantation in both patient groups, owing to a reduction in
      residual lumen obstruction, as determined by angiographic (%DS) and Doppler flow
      criteria (hyperemic blood flow velocity, relative CFR), and was associated with a
      decrease in MACE (16% vs. 7% in optimal BA group, p = 0.08; and 27% vs. 11% in
      suboptimal BA group, p = 0.007). CONCLUSIONS: Stent implantation enhances CFR
      after suboptimal and optimal Doppler-guided BA, owing to a reduction in residual
      lumen obstruction-determined by angiographical and Doppler flow criteria-as the
      underlying mechanism for an improved clinical outcome.

PMID- 11985917
TI  - A comparison of cardiac troponin T and creatine kinase-MB for patient evaluation
      after cardiac surgery.
AB  - OBJECTIVES: The aim of this study was to assess the role of serum markers of
      myocardial necrosis after cardiac surgery. BACKGROUND: The role of serum troponin
      T (TnT) and creatine kinase-MB (CK-MB) for the risk stratification of patients
      after cardiac surgery remains undefined. METHODS: Serum levels of TnT and CK-MB
      were measured from 224 patients every 8 h after cardiac surgery. The results of
      serum cardiac marker testing were correlated with adverse events, including new
      myocardial infarction (MI), cardiogenic shock or death. Univariable analysis
      identified factors predictive of complications, while stepwise logistic
      regression identified independent predictors of postoperative complications.
      RESULTS: Cardiac marker elevation was universal after cardiac surgery. At all
      time points measured, compared with those patients without complications, the TnT
      levels from patients with complications were more significantly elevated (all: p
      < 0.0005). In contrast, among identically timed specimens, the levels of CK-MB
      from complicated patients were less reliably discriminatory. Multivariable
      analysis suggested that a TnT level in the highest quintile (> or = 1.58 ng/ml)
      was the strongest predictor of complications, including death (post-op, odds
      ratio [OR] = 31.0, 95% confidence interval [CI] = 3.67 to 263.1, p = 0.002) or
      shock (post-op: OR = 18.9, 95% CI = 2.29 to 156.1, p = 0.006; 18 h to 24 h: OR =
      30.7, 95% CI = 3.75 to 250.7, p = 0.001), as well as the composite end points of
      death/MI (18 h to 24 h: OR = 60.1, 95% CI = 7.34 to 492.1, p < 0.0005), shock/MI
      (post-op: OR = 23.3, 95% CI = 2.82 to 191.4, p = 0.003; 18 h to 24 h: OR = 37.8,
      95% CI = 4.66 to 307.3, p = 0.001) or death/shock/MI (post-op: OR = 20.0, 95% CI
      = 2.81 to 142.0, p = 0.003; 18 h to 24 h: OR = 67.4, 95% CI = 6.96 to 652.3, p <
      0.0005). In contrast, in the presence of TnT, the results of CK-MB measurement
      added no independent prognostic information. CONCLUSIONS: Troponin T is superior
      to CK-MB for the prediction of impending complications after cardiac surgical
      procedures.

PMID- 11985918
TI  - Inter-relations among declines in arterial distensibility, baroreflex function
      and respiratory sinus arrhythmia.
AB  - OBJECTIVES: We hypothesized that structural and neural cardiovascular (CV)
      deficits may be intimately linked. Specifically, decreased carotid distensibility
      with age may blunt the arterial baroreflex, thereby reducing resting cardiac
      vagal tone. BACKGROUND: Increased CV risk is associated with lower carotid
      distensibility, impaired baroreflex function and reduced respiratory sinus
      arrhythmia (RSA), possibly representing a direct path between structural and
      neural CV deficits. METHODS: We estimated the mechanostructural and neural
      components of baroreflex function and examined their relation to RSA in young (20
      to 31 years) and older (59 to 71 years) subjects rigorously screened for CV and
      autonomic diseases. RESULTS: In the older subjects, RSA was < 20% of that in the
      younger subjects. Moreover, mechanical transduction of pressure into barosensory
      vessel stretch was approximately 40% lower (p < 0.05) and arterial baroreflex
      gain more than 60% lower (p < 0.05) in the older group. Although neural
      transduction of stretch into vagal outflow only tended to be less (p < 0.08), it
      was an important determinant of baroreflex function. A path analysis model showed
      comparable contributions of both the mechanical and neural components to
      baroreflex gain; however, lower overall baroreflex gain in the older group did
      not relate to lower RSA. CONCLUSIONS: These data suggest that decreased carotid
      distensibility does reduce baroreflex function with age, but this does not lead
      to reduced resting vagal outflow.

PMID- 11985919
TI  - Time to onset of regional relaxation: feasibility, variability and utility of a
      novel index of regional myocardial function by strain rate imaging.
AB  - OBJECTIVES: Time to onset of regional relaxation (T(R)) has been proposed as a
      novel index of regional myocardial function. This study sought to prospectively
      establish the feasibility and variability of T(R) in healthy volunteers (CONTROL)
      and to examine its utility in patients with inducible ischemia (PATIENT).
      BACKGROUND: Strain rate imaging (SRI) depicts myocardial deformation and enables
      quantitation of regional myocardial function with high temporal and spatial
      resolution. Thus, regional mechanical events can be accurately timed with SRI.
      The time point of regional transition from contraction to relaxation is altered
      in pathologic states. METHODS: Resting mean segmental T(R) was determined in 60
      subjects: 20 in the CONTROL group and 40 in the PATIENT group. T(R) was also
      measured at peak dobutamine stress in the PATIENT group. An automated image
      analysis program determined the time point of transition from regional
      contraction to relaxation activity, and calculated T(R), defined as the time, in
      milliseconds, from the electrocardiogram R-wave to this transition point.
      RESULTS: Automated T(R) measurements were feasible in more than 90% of the
      segments in CONTROL and PATIENT groups. Mean T(R) was 353 +/- 24 ms and was
      shorter in the mid segments compared to apical and basal segments. Intra- and
      interobserver variability were low (6% and 9%, respectively). In the PATIENT
      group, the percent decrease in T(R) during dobutamine stress was significantly
      higher in normal compared to ischemic segments (30% vs. 19%, respectively, p =
      0.01). A percent change >20% in T(R) identified patients with an ischemic
      response during dobutamine infusion (sensitivity 92%, specificity 75%).
      CONCLUSIONS: T(R), a novel quantitative index of regional myocardial function,
      can be determined with low variability and satisfactory feasibility in routine
      clinical settings. Percent change in T(R) identifies ischemic segments during
      dobutamine stress echocardiography (DSE) and may allow quantitative assessment of
      DSE.

PMID- 11985920
TI  - Vascular remodeling during healing after myocardial infarction in the dog model:
      effects of reperfusion, amlodipine and enalapril.
AB  - OBJECTIVES: We sought to determine whether reperfusion and the calcium channel
      blocker amlodipine or the angiotensin-converting enzyme inhibitor enalapril,
      during healing over six weeks after myocardial infarction (MI), limit structural
      vascular remodeling in the noninfarct zone (NIZ). BACKGROUND: The effect of
      reperfusion and amlodipine or enalapril on structural vascular remodeling during
      healing of MI has not been determined. METHODS: We randomly assigned 54 dogs to
      reperfused or nonreperfused MI, followed by twice-daily doses of oral placebo,
      amlodipine (5 mg) or enalapril (5 mg) for six weeks and three days off treatment,
      or to three matching sham groups. We measured in vivo hemodynamic data and left
      ventricular (LV) function and remodeling (by echocardiography) over the six
      weeks, as well as ex vivo structural vascular, ventricular and collagen
      remodeling in the hearts after six weeks. RESULTS: Compared with placebo and sham
      groups, both amlodipine and enalapril with or without reperfusion produced LV
      unloading and limited structural LV remodeling and dysfunction over six weeks in
      vivo, and also decreased the NIZ resistance vessel media/lumen area ratio at six
      weeks ex vivo. In addition, amlodipine, but not enalapril, preserved infarct scar
      collagen and increased the border zone collagen volume fraction and perivascular
      fibrosis, as well as NIZ resistance vessel media thickness. Enalapril, but not
      amlodipine, decreased transforming growth factor-beta in the border zone and NIZ.
      CONCLUSIONS: The results indicate that therapy with amlodipine and enalapril
      during healing after reperfused MI limits structural vascular remodeling in the
      NIZ, probably by different mechanisms.

PMID- 11985921
TI  - Contrast echocardiography can assess risk area and infarct size during coronary
      occlusion and reperfusion: experimental validation.
AB  - OBJECTIVES: We sought to validate the ability of real-time myocardial contrast
      echocardiography (MCE) measures of opacification defect and contrast refilling
      parameters to estimate risk area (RA) and infarct area (IA) during coronary
      occlusion and reperfusion. BACKGROUND: No data exist establishing the accuracy of
      MCE in determining RA and IA size. We hypothesized that in the setting of
      coronary occlusion, MCE should identify RA as a perfusion defect early after
      bubble destruction, collateral flow to viable myocardium as opacification late
      during refilling and IA as absent opacification. METHODS: Three hours of coronary
      occlusion and reperfusion were each produced in 11 dogs in which real-time MCE
      was performed during intravenous infusion of Sonovue (Bracco). Real-time contrast
      echocardiography was performed at baseline, during occlusion and reperfusion.
      Early (BEGIN) and end (END) images from a FLASH refilling sequence were acquired,
      as well as late refilling images (LATE) 1 min after FLASH. Real-time contrast
      echocardiography defect size and quantitative refilling parameters were compared
      with RA and IA determined by tissue staining. RESULTS: During occlusion, defect
      size varied with refilling time; defects from BEGIN images correlated best to RA
      and those from LATE images to IA. Refilling parameters, but not LATE peak
      intensity, did not predict the IA size during occlusion. During reperfusion,
      defects from BEGIN images were well correlated to RA and END images to IA,
      whereas peak plateau intensity and refilling slope parameters predicted IA size.
      CONCLUSIONS: Real-time contrast echocardiography defect size varies throughout
      microbubble refilling. Appropriately selected defect sizes and refilling
      parameters provide estimates of RA and IA during coronary occlusion and
      reperfusion.

PMID- 11985922
TI  - Chronic endothelin receptor antagonism prevents coronary vasa vasorum
      neovascularization in experimental hypercholesterolemia.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that endothelin
      (ET) receptor antagonism reduces coronary vasa vasorum neovascularization in
      experimental hypercholesterolemia. BACKGROUND: Experimental hypercholesterolemia
      is associated with increased expression of ET-1, an endothelium-derived peptide
      with vasoconstricting, mitogenic and angiogenic properties, in the coronary
      arterial wall as well as with vasa vasorum neovascularization. A pathomechanistic
      role of the endogenous ET system in vasa vasorum neovascularization in
      hypercholesterolemia has, however, remained uncertain so far. METHODS: Female
      domestic pigs were placed on a normal diet (N; n = 7) or on a
      hypercholesterolemic diet without (HC; n = 6) or with ET-A receptor antagonism
      (ABT-627, 4 mg/kg/day; HC + ET-A; n = 6). After 12 weeks, coronary vasa vasorum
      structure was assessed by three-dimensional microscopic computed tomography,
      expression of vascular endothelial growth factor (VEGF) within the coronary
      arterial wall by Western blotting and immunostaining. RESULTS: Compared with the
      N group, plasma concentrations of low-density lipoprotein cholesterol were higher
      in both the HC and HC + ET-A groups (36 +/- 3 mg/dl vs. 312 +/- 153 mg/dl and 303
      +/- 113 mg/dl, p < 0.01). Vasa vasorum density was higher in the HC group
      compared with the N group (4.7 +/- 1.8 per mm(2) vs. 2.5 +/- 1.5 per mm(2); p <
      0.05) and was preserved in the HC + ET-A group (3.2 +/- 0.7 per mm(2)). In
      parallel, increase in VEGF expression in the coronary arterial wall in the HC
      group was preserved in the HC + ET-A group. CONCLUSIONS: The current study
      demonstrates that chronic endothelin receptor antagonism prevents the increase in
      VEGF expression and vasa vasorum density of coronary arteries in experimental
      hypercholesterolemia. These findings support a role for the endogenous ET system
      in vasa vasorum neovascularization in early coronary atherosclerosis.

PMID- 11985924
TI  - Obesity, weight reduction and survival in heart failure.

PMID- 11985926
TI  - Ischemic cardiomyopathy: a historical note.

PMID- 11985927
TI  - Is early invasive treatment of unstable coronary artery disease equally effective
      for both women and men?

PMID- 11985929
TI  - Working toward the next generation of diabetes self-management education.

PMID- 11985930
TI  - Striving for a more active community. Lessons from the diabetes prevention
      program and beyond.

PMID- 11985931
TI  - Translating evidenced-based physical activity interventions into practice. The
      2010 challenge.

PMID- 11985932
TI  - Recommendations for healthcare system and self-management education interventions
      to reduce morbidity and mortality from diabetes.

PMID- 11985933
TI  - The effectiveness of disease and case management for people with diabetes. A
      systematic review.
AB  - This report presents the results of a systematic review of the effectiveness and
      economic efficiency of disease management and case management for people with
      diabetes and forms the basis for recommendations by the Task Force on Community
      Preventive Services on the use of these two interventions. Evidence supports the
      effectiveness of disease management on glycemic control; on screening for
      diabetic retinopathy, foot lesions and peripheral neuropathy, and proteinuria;
      and on the monitoring of lipid concentrations. This evidence is applicable to
      adults with diabetes in managed care organizations and community clinics in the
      United States and Europe. Case management is effective in improving both glycemic
      control and provider monitoring of glycemic control. This evidence is applicable
      primarily in the U.S. managed care setting for adults with type 2 diabetes. Case
      management is effective both when delivered in conjunction with disease
      management and when delivered with one or more additional educational, reminder,
      or support interventions.

PMID- 11985934
TI  - Increasing diabetes self-management education in community settings. A systematic
      review.
AB  - This report presents the results of a systematic review of the effectiveness and
      economic efficiency of self-management education interventions for people with
      diabetes and forms the basis for recommendations by the Task Force on Community
      Preventive Services. Data on glycemic control provide sufficient evidence that
      self-management education is effective in community gathering places for adults
      with type 2 diabetes and in the home for adolescents with type 1 diabetes.
      Evidence is insufficient to assess the effectiveness of self-management education
      interventions at the worksite or in summer camps for either type 1 or type 2
      diabetes or in the home for type 2 diabetes. Evidence is also insufficient to
      assess the effectiveness of educating coworkers and school personnel about
      diabetes.

PMID- 11985935
TI  - Recommendations to increase physical activity in communities.

PMID- 11985936
TI  - The effectiveness of interventions to increase physical activity. A systematic
      review.
AB  - The Guide to Community Preventive Service's methods for systematic reviews were
      used to evaluate the effectiveness of various approaches to increasing physical
      activity: informational, behavioral and social, and environmental and policy
      approaches. Changes in physical activity behavior and aerobic capacity were used
      to assess effectiveness. Two informational interventions ("point-of-decision"
      prompts to encourage stair use and community-wide campaigns) were effective, as
      were three behavioral and social interventions (school-based physical education,
      social support in community settings, and individually-adapted health behavior
      change) and one environmental and policy intervention (creation of or enhanced
      access to places for physical activity combined with informational outreach
      activities). Additional information about applicability, other effects, and
      barriers to implementation are provided for these interventions. Evidence is
      insufficient to assess a number of interventions: classroom-based health
      education focused on information provision, and family-based social support
      (because of inconsistent findings); mass media campaigns and college-based health
      education and physical education (because of an insufficient number of studies);
      and classroom-based health education focused on reducing television viewing and
      video game playing (because of insufficient evidence of an increase in physical
      activity). These recommendations should serve the needs of researchers, planners,
      and other public health decision makers.

PMID- 11985937
TI  - Impact of oral L-glutamine on glutathione, glutamine, and glutamate blood levels
      in volunteers.
AB  - OBJECTIVE: We investigated the effect of glutamine supplementation on plasma
      glutamine (Gln), glutamate (Glu), and whole-blood glutathione (GSH)
      concentrations in human volunteers. METHODS: Subjects first adapted to a standard
      diet with known intakes of protein, total GSH, cysteine, methionine, and total
      Glu (Glu values include Glu and Gln) for 3 d. Plasma Gln, Glu, and whole-blood
      GSH levels were then measured at 4-h intervals over 24 h. Supplemental oral Gln
      (0.3 g x kg(-1) x d(-1)) was ingested for 10 d and then 24-h plasma levels of
      Gln, Glu, and whole-blood GSH were measured. RESULTS: The plasma concentrations
      of Glu (116%; P = 0.006) and Gln (20%; P = 0.046) were significantly higher,
      whereas concentrations of GSH were significantly lower (37%; P = 0.00091) after
      oral Gln supplementation. CONCLUSION: Oral Gln increases Glu and Gln levels in
      plasma of healthy subjects but does not increase GSH red cell (whole-blood)
      levels. Thus, GSH biosynthesis and preservation of GHS stores in red blood cells
      may involve rate-limiting substrates other than Gln.

PMID- 11985938
TI  - Can glutamine modify the apparent immunodepression observed after prolonged,
      exhaustive exercise?
AB  - Glutamine is an important fuel for some cells of the immune system. In situations
      of stress, such as clinical trauma, starvation, or prolonged, strenuous exercise,
      the concentration of glutamine in blood is decreased, often substantially. In
      endurance athletes this decrease occurs concomitantly with relatively transient
      immunodepression. Provision of glutamine or a glutamine precursor has been found
      to decrease the incidence of illness in endurance athletes. To date, it has not
      been established precisely which aspect of the immune system is affected by
      glutamine feeding during the transient immunodepression that occurs after
      prolonged, strenuous exercise. However, there is increasing evidence that
      neutrophils may be implicated.

PMID- 11985939
TI  - Branched-chain amino acid supplementation and the immune response of long
      distance athletes.
AB  - OBJECTIVE: Intense long-duration exercise has been associated with
      immunosuppression, which affects natural killer cells, lymphokine-activated
      killer cells, and lymphocytes. The mechanisms involved, however, are not fully
      determined and seem to be multifactorial, including endocrine changes and
      alteration of plasma glutamine concentration. Therefore, we evaluated the effect
      of branched-chain amino acid supplementation on the immune response of
      triathletes and long-distance runners. METHODS: Peripheral blood was collected
      prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte
      proliferation, cytokine production by cultured cells, and plasma glutamine were
      measured. RESULTS: After the exercise bout, athletes from the placebo group
      presented a decreased plasma glutamine concentration that was abolished by
      branched-chain amino acid supplementation and an increased proliferative response
      in their peripheral blood mononuclear cells. Those cells also produced, after
      exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and
      48% more interleukin-2. Supplementation stimulated the production of interleukin
      2 and interferon after exercise and a more pronounced decrease in the production
      of interleukin-4, indicating a diversion toward a Th1 type immune response.
      CONCLUSIONS: Our results indicate that branched-chain amino acid (BCAA)
      supplementation recovers the ability of peripheral blood mononuclear cells
      proliferate in response to mitogens after a long distance intense exercise, as
      well as plasma glutamine concentration. The amino acids also modify the pattern
      of cytokine production leading to a diversion of the immune response toward a Th1
      type of immune response.

PMID- 11985940
TI  - Early postoperative feeding and outcome in neonates.
AB  - OBJECTIVES: The results of neonatal surgery in the Western world have rapidly
      improved over the past three decades. Early nutrition support is thought to be
      one of the key factors. We used transgastric, transanastomotic feeding
      jejunostomy tubes in every infant undergoing upper gastrointestinal surgery when
      the expected period of fasting has exceeded 7 d. METHODS: Newborns with duodenal
      atresia, malrotation, and jejunal atresia were treated consecutively between
      November 1998 and November 1999. We analyzed the outcome of such a practice.
      There were 17 consecutive babies recruited into the study. Ten babies had
      duodenal atresia, one associated with esophageal atresia and tracheo-esophageal
      fistula, six had malrotation, and one had jejunal atresia. The weights of the
      babies varied between 1.2 and 3.78 kg (mean = 2.1 kg) and they were referred
      between the ages of 1 and 23 d. Three babies were younger than 32 wk of gestation
      and weighed less than 1.5 kg; all had multiple bowel atresia, including one with
      associated pyloric atresia. None of these three survived. Enteral feeding was
      started by postoperative day 2 in 14 cases. Period of feeding varied between 3
      and 20 d, with a mean of 10.4 d in the surviving babies. Three of the tubes had
      minor mechanical complications. RESULTS: The weight loss or gain during the
      period of hospitalization was not significant (P = 0.3) Breast milk was the most
      common nutrient. Thirteen of the 14 babies weighing more than 1.5 kg were
      discharged and are being followed; the remaining baby died from neonatal
      septicemia. Excellent results can be obtained with aggressive enteral nutrition
      support in newborns undergoing upper intestinal surgery. CONCLUSIONS:
      Transgastric, transanastomotic feeding jejunostomy was well tolerated by the
      newborns and is preferable to parenteral nutrition.

PMID- 11985941
TI  - Reference values of the bioelectrical impedance vector in neonates in the first
      week after birth.
AB  - OBJECTIVE: To determine the reference, bivariate, tolerance intervals of the
      whole-body impedance vector for healthy white neonates, we performed an
      observational, cross-sectional study in two university hospitals. METHODS: The
      impedance vector (standard, tetrapolar analysis at 50-kHz frequency) was measured
      in 163 consecutive subjects (87 boys and 76 girls) with postnatal ages of 1 to 7
      d. Bivariate vector analysis was conducted with the resistance-reactance (RXc)
      graph method. RESULTS: The age-specific 95% confidence intervals of mean vectors
      and the 95%, 75%, and 50% tolerance intervals for individual vector measurements
      were plotted using R and Xc components standardized by the subject's crown-to
      heel length (height). Mean vectors from the groups (1, 2, and 3 to 7 d) with
      overlapping 95% confidence ellipses were considered representative of only one
      age class of 1 to 7 d. The impedance vector distribution of neonates also was
      compared with healthy white children (1014 boys and 1030 girls, age 2-15 y) and
      adult subjects (354 men and 372 women, age 15-85 y) from the same geographic
      area. There was a definite, progressive, vector shortening from birth, through
      ages 2 to 15 y, toward the adults' vector position. CONCLUSIONS: We established
      the reference, bivariate, 95%, 75%, and 50% tolerance intervals of the impedance
      vector in the first postnatal week for healthy white neonates, with which the
      vectors from infants with altered body composition can be tested (free software
      is available from apiccoli@ unipd.it).

PMID- 11985942
TI  - Effects of a milk-based bioactive micronutrient beverage on pain symptoms and
      activity of adults with osteoarthritis: a double-blind, placebo-controlled
      clinical evaluation.
AB  - OBJECTIVES: A 6 wk, double-blind, placebo-controlled study investigated the
      effects of a nutritional supplement beverage containing milk-based micronutrients
      and fortified with vitamins and minerals on pain symptoms and activity in adults
      with osteoarthritis. METHODS: Thirty-one subjects with osteoarthritis of both
      knees were randomized into two groups and given 12 oz daily of the micronutrient
      containing beverage or a placebo for 6 wk. Subjects were instructed not to change
      their normal activities and diets. Body weights, vital signs, blood chemistries,
      and adverse events were monitored to assess safety. The principal outcome
      measurement for efficacy was the Western Ontario MacMaster Universities
      Osteoarthritis Index (WOMAC) derived from the Knee Injury and Osteoarthritis
      Outcome Score (KOOS) questionnaire administered weekly. RESULTS: Safety
      indicators remained unchanged in the test and placebo groups. All KOOS scores
      improved significantly (P < 0.03) over time in the micronutrient group, whereas
      scores only for sport function and knee-related quality of life improved in the
      placebo group. The overall treatment effect (based on changes in the WOMAC
      composite score) was significant (P = 0.016). The effect size was moderate at
      0.555. CONCLUSIONS: Thus, daily consumption of the nutritional beverage
      containing milk-based micronutrients, vitamins, and minerals was beneficial in
      alleviating symptoms and dysfunction in subjects with osteoarthritis.

PMID- 11985943
TI  - Use of fermented foods to combat stunting and failure to thrive.
AB  - OBJECTIVES: With the adoption of vigorous child survival strategies, infant and
      child mortalities in India have declined significantly, even among the poorest,
      most undernourished segments of the population. Of the surviving infants and
      children, however, many remain stunted and undernourished. The present study was
      based on the hypothesis that failure to thrive is the result of damage to the gut
      epithelium incurred during repeated bouts of gastrointestinal infections.
      Promoting the regeneration of the damaged gut epithelium through the use of
      lactobacillus-rich fermented foods may yield beneficial results. This low-cost
      procedure can be widely used, even in poor communities. The objectives of this
      study were to investigate the effect in poor Indian communities of
      supplementation with a probiotic on the growth of children (aged 2 to 5 years)
      with growth retardation and assess the difference in morbidity between those
      receiving the supplement (n = 50) and the control group (n = 50), mainly with
      respect to the frequency, severity, and duration of diarrheal episodes. METHODS:
      One hundred children aged 2 to 5 y from an urban slum of New Delhi were matched
      for their age (+/-36 d), sex and weight (+/-1 kg) and assigned to one of two
      groups (experimental n= 50 and control n= 50). The experimental group received a
      probiotic supplement (50 ml curd containing Lactobacillus acidophilus) and the
      control group received an isocaloric supplement daily for 6 mo. Weight, height,
      and morbidity profile with respect to diarrhea, fever, cough, and cold was
      recorded. RESULTS: Increases in weight (P < 0.002) and height (P < 0.001) were
      significantly greater in the experimental group than in the control group. In
      addition, after 6 mo, of supplementation, there were fewer cases of diarrhea (P <
      0.005) and fever (P < 0.001) in the intervention group then in the control group.
      CONCLUSIONS: From this study, it can be concluded that 6 mo of probiotic
      supplementation may be beneficial with respect to decrease in diarrheal morbidity
      and accelerated growth in the experimental group.

PMID- 11985944
TI  - Effect of creatine loading on anaerobic performance and skeletal muscle volume in
      NCAA Division I athletes.
AB  - OBJECTIVE: We measured the effect of 3 d of creatine (Cr) supplementation on
      repeated sprint performance and thigh muscle volume in elite power athletes.
      METHODS: Ten male (mean +/- standard deviation of body mass and percentage of fat
      (81.1 +/- 10.5 kg and 9.8 +/- 3.5) and ten female (58.4 +/- 5.3 kg and 15.0 +/-
      3.4) athletes were matched for sex and 10-s cycle sprint scores, paired by rank,
      and randomly assigned to the Cr or placebo (P) group. Subjects completed six
      maximal 10-s cycle sprints interspersed with 60 s of recovery before and after 3
      d of Cr (0.35 g/kg of fat-free mass) or P (maltodextrin) ingestion. Before and
      after supplementation, 10 contiguous transaxial images of both thighs were
      obtained with magnetic resonance imaging. RESULTS: Cr supplementation resulted in
      statistically significant increases in body mass (0.9 +/- 0.1 kg, P < 0.03),
      total work during the first sprint (P < 0.04), and peak power during sprints 2 to
      6 (P < 0.10). As expected, total work and peak power values for males were
      greater than those for their female counterparts during the initial sprint (P <
      0.02); however, the reverse was true during the last three sprints (P < 0.01).
      Imaging data showed a 6.6% increase in thigh volume in five of six Cr subjects (P
      = 0.05). CONCLUSION: These data indicate that 3 d of Cr supplementation can
      increase thigh muscle volume and may enhance cycle sprint performance in elite
      power athletes; moreover, this effect is greater in females as sprints are
      repeated.

PMID- 11985945
TI  - Homocysteine and psychological traits: a study in obesity.
AB  - OBJECTIVE: Total serum homocysteine is a risk factor for cardiovascular disease
      in the general population. Further, homocysteine might be the link between
      psychological traits (namely anger and hostility) and cardiovascular disease,
      mediated by stressful events and sympathetic nervous tone. METHODS: We measured
      total plasma homocysteine levels and psychological traits in 205 obese
      individuals entering a weight-reduction program (162 females; age range, 17-64
      years; body mass index, 37.7 +/- 6.2 kg/m(2), mean +/- standard deviation).
      Psychometric assessment was performed with three self-administered questionnaires
      (Symptom Checklist 90, composed of nine subscales including Hostility/Anger and
      Depression scales; Beck Depression Inventory; and Binge Eating Scale). RESULTS:
      Homocysteine levels were moderately increased in obese individuals when compared
      with the normal population and higher in males (median, 12.9 micromol/L; range,
      6.9-26.3) than in females (9.8; 4.6-24.6; P < 0.0002), but not different in
      relation to the severity of obesity. Serum folate and vitamin B12 were normal.
      Psychometric testing showed pathologic data in up to 50% of patients and the
      Anger/Hostility scale was positive in 24%, mainly female, subjects. There were no
      differences in psychological traits in relation to the severity of obesity.
      Homocysteine did not correlate with Symptom Checklist 90 values or other values
      of psychometric testing. CONCLUSIONS: In obese persons, psychological traits are
      not major determinants of total homocysteine. A different response to stressful
      events, not simply mediated by sympathetic nervous tone, might be present in
      obesity.

PMID- 11985946
TI  - Prevalence of decubitus ulcer and associated risk factors in an institutionalized
      Spanish elderly population.
AB  - OBJECTIVE: We investigated the prevalence and associated risk factors of
      decubitus ulcer in an institutionalized Spanish elderly population. METHODS: A 1
      d cross-sectional study in 50 Spanish geriatric facilities was carried out. Data
      collection included age, sex, body mass index, presence of decubitus ulcer,
      duration of ulcer, days of hospitalization, risk according to the Norton scale,
      associated risk factors, and nutrition status evaluation including assessment
      according to the Nutrition Screening Initiative. Logistic regression analysis
      calculated prevalence and association with risk factors. RESULTS: Data from 827
      elderly people (71.3% female) were collected. Mean age (+/- standard deviation)
      was 82.4 (+/-8.0) y. Decubitus ulcer prevalence was 35.7%, with no sex
      differences (34.1% males and 37.2% females). Body mass index was inversely
      associated with ulcer prevalence in a statistically significant way (odds ratio =
      0.94, 95% confidence interval = 0.92-0.97), but the following were risk factors:
      age (1.03, 1.01-1.06), previous ulcer (3.09, 2.16-4.04), diabetes (1.54, 1.02
      2.51), functionality (2.91, 2.05-4.12), immobility (8.30, 5.09-11.51), erythema
      (12.12, 7.46-16.78), dehydration (2.09, 1.31-2.87), and edema (2.35, 1.64-3.06).
      Subjective evaluation of nutrition status and nutrition status as assessed by the
      Nutrition Screening Initiative Determine scale (modified) showed a significant
      linear association with ulcer (P < 0.001), and a score above 14 points in the
      modified Norton scale was associated with a lower ulcer rate (P < 0.001).
      CONCLUSIONS: Prevalence of decubitus ulcer in the Spanish elderly population
      increased with age, poor nutrition status, immobilization, and impaired
      functionality.

PMID- 11985947
TI  - Fish as a major source of vitamin D in the Japanese diet.
AB  - OBJECTIVES: We investigated the amount and sources of vitamin D in the Japanese
      diet by analyzing diet records collected over a 4-mo period. METHODS: Dietary
      data for this study were provided by a nursing home in Niigata, Japan. Diet
      records, written by the nursing home's dietitian, for 122 consecutive days
      between September and December 1999, were used. The amount of food for an
      individual was weighed before cooking and recorded on the diet record. Vitamin D
      containing foods, including fish, eggs, meat, and mushrooms, were selected from
      the diet records, and their vitamin D (vitamin D2 plus D3) per day was calculated
      by referring to the Standard Tables of Food Composition in Japan. RESULTS: The
      overall average vitamin D intake per day was 7.10 microg (284 IU), which is about
      70% of the recommended dietary allowance of 10 microg (400 IU). There were no
      significant differences in vitamin D values over the 4 mo (P = 0.822). Overall,
      the contribution of vitamin D from fish to total vitamin D intake was 90.7%,
      followed by mushrooms (4.4%), eggs (3.2%), and meat (1.7%). CONCLUSIONS: Frequent
      fish intake appears to be an advisable health practice in terms of preventing
      vitamin D insufficiency in the elderly.

PMID- 11985948
TI  - Obesity and gender differences in the risk of type 2 diabetes mellitus in Uganda.
AB  - OBJECTIVE: We assessed the severity of type 2 diabetes in urban and rural
      communities of Uganda and characterized this disease according to sex, obesity,
      and hypertension. METHODS: A total of 440 subjects was tested for high blood and
      urine glucose levels with the respective glucometers and sample strips. Body mass
      index and hypertension were determined by measuring height, weight, and blood
      pressure. RESULTS: In a random study conducted in the communities of the
      districts of Kampala and Mokono, the prevalence of type 2 diabetes was found to
      be about 8.1% (n = 148). An association between obesity, hypertension, and risk
      of type 2 diabetes was found among the women, of whom nearly 80% were overweight.
      However, the men, who were primarily lean, did not exhibit this same correlation.
      CONCLUSIONS: These epidemiologic data suggest a variance from the strong
      correlation of type 2 diabetes and obesity seen in Western countries and most of
      Europe. Specifically, the etiology of this disease in Uganda is different between
      men and women. The reasons for this phenomenon are not well elucidated, but it is
      likely that a long history of obesity in women may genetically or environmentally
      predispose them to this disease.

PMID- 11985949
TI  - Physical inactivity is the major determinant of obesity in black women in the
      North West Province, South Africa: the THUSA study. Transition and Health During
      Urbanisation of South Africa.
AB  - OBJECTIVE: We investigated the association between measures and determinants of
      obesity in African women. METHODS: For a cross-sectional study of adult black
      women in the North West Province, South Africa, we used a stratified sample of
      1040 volunteers from 37 randomly selected sites in the province according to the
      level of urbanization. We analyzed the association between measures of obesity,
      namely body mass index (BMI), waist circumference, waist-to-hip ratio, triceps
      and subscapular skinfolds, and socioeconomic factors, dietary intakes, and
      physical activity. RESULTS: The rate of obesity (BMI > 30) in the sample was
      28.6%. We found a significant positive association between household income and
      measures of obesity. After exclusion of underreporters and adjustments for age,
      smoking, and household income, we found significant positive correlations between
      total energy intake, fat intake, and BMI. Physical activity index (derived from a
      subset of 530 subjects) correlated negatively with BMI and waist circumference.
      Subjects in the highest third of physical activity were less likely to be obese
      (odds ratio-0.38, 95% confidence interval-0.22-0.66). CONCLUSIONS: Women with
      higher incomes and lower physical activity were at the greatest risk of increased
      BMI. Physical inactivity showed the strongest association with measures of
      obesity in this study.

PMID- 11985950
TI  - Effect of treatment with folic acid and vitamin B6 on lipid and homocysteine
      concentrations in patients with coronary artery disease.

PMID- 11985951
TI  - Obesity, metabolic syndrome X, and inflammation.

PMID- 11985952
TI  - Red wine consumption and brain aging.

PMID- 11985953
TI  - Glutamine and gut barrier function.

PMID- 11985954
TI  - Nutrition, cancer, and children.

PMID- 11985955
TI  - Bacterial translocation and glutamine.

PMID- 11985956
TI  - Prevalence of decubitus ulcer and associated risk factors in an institutionalized
      Spanish elderly population.

PMID- 11985957
TI  - Estimating energy and protein requirements of thermally injured patients: art or
      science?

PMID- 11985958
TI  - Tea as a functional food for oral health.

PMID- 11985959
TI  - Route of nutrition support.

PMID- 11985960
TI  - A trawl through the current nutrition literature.

PMID- 11985961
TI  - Evaluation of integral membrane antigens of Mycobacterium habana for
      serodiagnosis of extrapulmonary tuberculosis: association between levels of
      antibodies and Mycobacterium tuberculosis antigens.
AB  - The performance of integral membrane antigens (IMAs) of Mycobacterium habana TMC
      5135 in detecting antimycobacterial antibodies in serum and body fluids of
      patients mainly of extrapulmonary tuberculosis was evaluated. The IMAs were
      recovered from the detergent phase during Triton X-114 treatment of the plasma
      membrane of M. habana. Antimycobacterial antibodies were detected by ELISA using
      IMAs in serum and body fluids of 42 patients and 62 control subjects. As
      authentic adjunct Mycobacterium tuberculosis antigens were also detected (by
      ELISA) in body fluids and circulating immune complexes using anti-M. tuberculosis
      H37Ra antibodies. Anti-M. habana IMA antibody detection increased the positivity
      rate from 26.% (11/42) and 10% (4/42) obtained by culture and smear microscopy,
      respectively, to 86% (36/42). M. tuberculosis antigens were also found in 29 out
      of 36 anti-M. habana IMA antibody-positive cases. Interestingly, all 11 culture
      positive cases were also positive for anti-M. habana IMA antibodies. The mean
      antigen titres in 23 cases, positive for antigens in body fluids, were 2.34 times
      higher in those who were also positive for anti-IMA antibodies in serum than in
      those negative for these antibodies. M. habana IMAs may be promising non
      tubercular candidate antigens in ELISA-based serodiagnosis of extrapulmonary
      tuberculosis with substantial sensitivity, specificity and safety.

PMID- 11985962
TI  - Immunogenic protein variations of Clostridium chauvoei cellular antigens
      associated with the culture growth phase.
AB  - The immunoprotective capacity of four Clostridium chauvoei strains at different
      growth stages is reported. In all the strains tested, the cells coming from the
      stationary phase were those with the highest immunoprotective capacity and,
      depending on the strain, this protective capacity diminished or even disappeared
      in other phases. Protein profiles were similar in all the strains and few
      proteins were differentially expressed during growth as shown by SDS-PAGE. For
      strain 17, a local strain, a clear relationship was observed between the
      diminution of immunogenicity and the total loss of protective capacity of
      sonicated cells at late stationary phase.

PMID- 11985963
TI  - Staphylococcal alpha-toxin synergistically enhances inflammation caused by
      bacterial components.
AB  - This study was performed to investigate the in vivo effects of staphylococcal
      alpha-toxin on phagocytosis and the secretion of proinflammatory cytokines at
      local sites of intraperitoneal toxin-challenged mice. A dosage of 45 hemolytic
      units (HU) of alpha-toxin induced a marked increase in the peritoneal neutrophil
      count. The toxin caused a 52% decrease in phagocytosis by peritoneal macrophages,
      compared with that of control mice receiving Staphylococcus aureus particles
      alone. However, no effect on phagocytosis in neutrophils was observed. A dosage
      of 45 HU toxin and the synergistic activity of S. aureus particles strongly
      induced interleukin (IL) 6 secretion but only mildly induced IL-1alpha secretion.
      The toxin did not induce the secretion of tumor necrosis factor-alpha (TNF
      alpha). Interestingly, S. aureus culture supernatant induced the secretion of TNF
      alpha in cultured macrophages. These results suggest that alpha-toxin damages the
      primary host defense system by inducing the oversecretion of IL-1alpha and IL-6,
      but not TNF-alpha, via a mechanism that requires the synergistic action of
      bacterial components.

PMID- 11985964
TI  - Type 1, P and S fimbriae, and afimbrial adhesin I are not essential for
      uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells.
AB  - Fimbrial (type 1, P, and S) and afimbrial adhesins, the unique virulence traits
      of uropathogenic Escherichia coli (UPEC), are well recognized for their role in
      the initial step of uropathogenesis. In this study, we investigated whether these
      adhesins are dispensable for UPEC in adherence and invasion of uroepithelial
      cells by using E. coli isolates (n=40) from cystitis patients and T-24 cells, the
      bladder carcinoma cell line. We found all isolates adherent to T-24 cells within
      15 min of infection. In invasion assay, all isolates could invade T-24 cells to a
      variable degree; 22.5% of them were found highly invasive. About 33% of isolates
      that do not have any recognized adhesins were as invasive as other isolates. The
      amplitude of invasiveness was also independent of the adhesins. In conclusion,
      this study demonstrates that type 1 fimbriae, P fimbriae, S fimbriae, and
      afimbrial adhesin I are not required for UPEC to adhere to and invade
      uroepithelial cells.

PMID- 11985965
TI  - Incidence of Norwalk-like viruses, rotavirus and adenovirus infection in patients
      with acute gastroenteritis in Jakarta, Indonesia.
AB  - Norwalk-like viruses (NLVs), rotavirus and adenovirus are reportedly responsible
      from 4 to 42% of non-bacterial acute sporadic gastroenteritis. The incidence of
      NLVs, adenovirus and rotavirus infections in Indonesia is unclear. A total of 402
      symptomatic cases from Indonesian patients with acute gastroenteritis and 102
      asymptomatic controls that tested negative for bacteria and parasites were
      screened for the presence of NLVs, rotavirus and adenovirus using the reverse
      transcriptase-polymerase chain reaction (RT-PCR), Rotaclone kits and Adenoclone
      kits. Specific prototype probes were used to ascertain which NLV prototypes were
      present in the area. NLVs were detected in 45/218 (21%), rotavirus was detected
      in 170/402 (42%) and adenovirus was detected in 11/273 (4%) samples examined.
      Genetic analysis of the RT-PCR products using specific prototype probes for NLVs
      indicated that the prototypes were 42% Taunton agent and 58% Hawaii/Snow Mountain
      agent. Comparative data on patients showed that the incidence of rotavirus
      infections was two times greater than the NLVs infections, and that adenovirus
      infections were the least prevalent. All of the control samples tested were
      negative for NLVs and adenoviruses, however 8/70 (11%) of the samples were
      positive for rotaviruses. The high incidence of enteric viral-related infections
      is a threat among acute diarrheic patients in Jakarta, Indonesia.

PMID- 11985966
TI  - Minor pilin subunits are conserved in Vibrio cholerae type IV pili.
AB  - The nucleotide sequences of five open reading frames within the Vibrio cholerae
      NAGV14 type IV pilus gene cluster were determined. The genes showed high homology
      to the mannose-sensitive hemagglutinin (MSHA) pilus genes mshB, mshC, mshD, mshO
      and mshP. PCR analysis showed that a MSHA-like gene cluster is highly conserved
      among different V. cholerae strains, with the exception of the previously
      reported major pilin subunit. Recombinant MshB and MshO proteins were purified
      and specific antiserum was raised to each of them. Western blotting analyses
      showed that these antisera reacted with purified NAGV14 and MSHA pili. The
      results suggested that MshB and MshO are minor components of the pilus fiber.
      Although there was no cross-reaction between the major pilin subunits of NAGV14
      and MSHA pili, minor components seemed to be highly homologous and
      immunologically cross-reactive.

PMID- 11985967
TI  - beta-1,3-Glucan reduces growth of Mycobacterium tuberculosis in macrophage
      cultures.
AB  - The effect of beta-1,3-D-glucans SSG, from Sclerotinia sclerotiorum, or soluble
      (sMG) or particulate (pMG) MacroGard from baker's yeast on growth of
      Mycobacterium tuberculosis H37Rv in cultures of peritoneal macrophages from
      BALB/c mice was examined. After 24 h intracellular bacteria from lysed
      macrophages were cultured and the number of cfu counted. SSG given with
      challenge, but not 24 h after, reduced the number of M. tuberculosis cfu
      significantly. pMG, but not sMG, given with challenge had an even stronger
      inhibitory effect, which was enhanced after serum opsonization of the particles.
      The effect of serum-treated pMG was abrogated by addition of a monoclonal
      antibody to CD11b. The results indicate that beta-glucans inhibit growth of M.
      tuberculosis in host cells in vitro, probably due to cellular stimulation and/or
      competitive inhibition of uptake of bacteria via CR3 (CD11b/18).

PMID- 11985968
TI  - The potentially insecticidal Narcissus pseudonarcissus lectin demonstrates age
      related mitogenicity.
AB  - Lectins from monocotyledonous plants such as Narcissus pseudonarcissus (NPA)
      possess insecticidal properties and have the potential to increase pest
      resistance in transgenic crops. Therefore it is of interest to investigate the
      mitogenic properties of such lectins. Mononuclear cells purified from human
      umbilical cord and adult peripheral blood samples were stimulated with NPA and
      compared to phytohaemagglutinin as an example of a lectin from a dicotyledonous
      plant. Here we report that NPA is slightly mitogenic for adult human lymphocytes
      but mitogenicity is increased more than sevenfold for lymphocytes from umbilical
      cord blood. Similarly, NPA was found to be mitogenic for peripheral blood
      mononuclear cells (PBMC) from lambs and not adult sheep, supporting the age
      related mitogenicity and indicating that further examination of the younger human
      population is warranted.

PMID- 11985969
TI  - Identification of a new segment involved in cagA 3' region variation of
      Helicobacter pylori.
AB  - The cagA 3' region shows marked variation among Helicobacter pylori strains. Two
      segments of 102 bp and 57 bp are reportedly responsible for this variation. We
      analysed the cagA 3' region in 70 H. pylori strains using polymerase chain
      reaction and sequencing. We found that another segment, namely beta segment, was
      also involved in the variation of this region. The beta segment was 105 bp long
      and located between the aforementioned two segments. Six genotypes were
      identified based on the structure of the cagA 3' region. No relationship was
      found between these genotypes and the clinical outcomes or vacA genotypes. The
      numbers of tyrosine phosphorylation sites within the cagA 3' region varied among
      strains, but this was not related to the cagA genotypes. Our data suggest that
      the cagA 3' region is significantly variable. It appears that the variation of
      the cagA 3' region might contribute to the modification of virulence.

PMID- 11985970
TI  - Assessment of antibody responses to antigens of Mycobacterium tuberculosis and
      Cysticercus cellulosae in cerebrospinal fluid of chronic meningitis patients for
      definitive diagnosis as TBM/NCC by passive hemagglutination and immunoblot
      assays.
AB  - Tanned sheep erythrocytes stabilized with pyruvic aldehyde and glutaraldehyde,
      called double-aldehyde-stabilized cells, were used to standardize passive
      hemagglutination assay (PHA) for detection of antibody responses to sonicate
      extract of Mycobacterium tuberculosis and Cysticercus cellulosae soluble
      antigens. PHA was performed in the following groups of cerebrospinal fluid (CSF)
      samples: group I - chronic infections of the central nervous system with the
      possible diagnosis of tuberculous meningitis (TBM), tuberculoma and
      neurocysticercosis (NCC) (n=88), and group II - controls which included (a) non
      infectious non-neurological conditions (n=30), (b) infectious neurological
      conditions (n=21) and (c) non-infectious neurological conditions (n=133). PHA
      could detect anti-mycobacterial antibodies at the sensitivity level of 80.76%
      with a specificity of 92.4% and anti-cysticercal antibodies with a sensitivity of
      100% and specificity of 92.94%. However, in 6.33% (i.e. 14/221) of group I and
      group II (c) CSFs both anti-mycobacterial and anti-cysticercal antibodies were
      detected. Immunoblot analysis of CSFs derived from TBM patients reacted
      predominantly to 120-kDa, 96-kDa, 65-kDa, 38-kDa, 26-kDa, 23-kDa, 19-kDa and 12
      14-kDa and 4-6-kDa antigens of M. tuberculosis sonicate extract (MTSE), whilst
      CSFs of proven NCC reacted to >110-kDa, 96-kDa, 80-kDa, 66-68-kDa, 52-kDa and 26
      28-kDa antigens of porcine whole cyst sonicate extract (PCSE). On immunoblot
      analysis, some of the CSFs of TBM patients were PHA positive for both MTSE and
      PCSE showed antibody reactivity to 70-kDa and 10-kDa antigens of C. cellulosae.
      Similarly CSF antibody of some Guillain Barre syndrome and myeloradiculopathy
      patients reacted with cysticercal antigens. But per se no cross-reactivity
      between MTSE and anti-cysticercal antibodies and vice-versa were observed.
      However, findings of this study should alert laboratory personnel especially in
      endemic areas to be extra careful in interpretation of antibody detection
      results.

PMID- 11985971
TI  - Comparison of Fonsecaea pedrosoi sclerotic cells obtained in vivo and in vitro:
      ultrastructure and antigenicity.
AB  - The parasitic form of Fonsecaea pedrosoi from the hyperkeratotic layer of the
      skin was obtained from four patients with chromoblastomycosis. Primary cultures
      containing hyphae and conidia were successfully converted into sclerotic cells in
      the presence of 800 microM propranolol and low pH as described before. The
      morphology of sclerotic cells of F. pedrosoi obtained in vivo and in vitro was
      analyzed by light and electron microscopy. Their antigenicity was also compared
      by immunofluorescence microscopy and ELISA assays, using serum samples from
      untreated patients infected with F. pedrosoi. Due to the similarity of the
      sclerotic cells obtained in vivo and in vitro, the latter can be more adequately
      in studies of host-parasite interactions in chromoblastomycosis.

PMID- 11985973
TI  - Renal cell carcinoma metastatic to the pancreas: results of surgical management.
AB  - Metastatic tumors to the pancreas are uncommon. Renal cell carcinoma is one of
      the few tumors known to metastasize to the pancreas. The purpose of the current
      report is to evaluate the surgical management and long-term outcome of patients
      with metastatic renal cell carcinoma. A retrospective review of patients
      undergoing pancreatic resection for renal cell carcinomas metastatic to the
      pancreas or periampullary region between April 1989 and May 1999, inclusive, was
      performed. Time from initial presentation, other metastatic sites, surgical
      outcomes, and long-term survival were evaluated. During the 10-year time period,
      10 patients underwent pancreatic resection for renal cell carcinoma metastases.
      Of those, six underwent pancreaticoduodenectomy and two underwent distal
      pancreatectomy, whereas the two remaining patients underwent total pancreatectomy
      for extensive tumor involvement throughout the entire gland. The mean time from
      nephrectomy for resection of the primary tumor to reoperation for periampullary
      recurrence was 9.8 years (median 8.5 years). The range was 0 to 28 years, with
      one patient presenting with a synchronous metastasis. The mean age of the
      patients was 61.2 years with 60% of patients being male and 90% being white.
      Pathologic findings included histologically negative lymph nodes and negative
      surgical margins in all patients. One patient had tumor involving the
      retroperitoneal soft tissue, but final margins were negative. The mean live
      patient follow-up was 30 months (median = 15 months), with eight patients
      remaining alive. The Kaplan-Meier actuarial 5-year survival was 75%, with the
      longest survivor still alive 117 months following resection. The patient with
      retroperitoneal soft tissue involvement died 4 months after resection. The
      pancreas is an uncommon site of metastasis for renal cell carcinoma, typically
      occurring years after treatment of the primary tumor. When the metastatic focus
      is isolated and the tumor can be resected in its entirety, patients can
      experience excellent 5-year survival rates. The current report suggests that
      pancreatic metastases from renal cell carcinoma should be managed aggressively
      with complete resection when possible.

PMID- 11985972
TI  - Post-ERCP pancreatitis: reduction by routine antibiotics.
AB  - Cholangitis and pancreatitis are severe complications of endoscopic retrograde
      cholangiopancreatography (ERCP). Antibiotics have been considered important in
      preventing cholangitis, especially in those with jaundice. Some have suggested
      that bacteria may play a role in the induction of post-ERCP pancreatitis. It is
      not clear, however, whether the incidence of post-ERCP pancreatitis could be
      reduced by antibiotic prophylaxis, as is the case with septic complications. In
      this prospective study, a total of 321 consecutive patients were randomized to
      the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of
      cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n =
      160) that received no antibiotics. All patients admitted to the hospital for ERCP
      who had not taken any antibiotics during the preceding week were included.
      Patients who were allergic to cephalosporins, patients with immune deficiency or
      any other condition requiring antibiotic prophylaxis, patients with clinical
      jaundice, and pregnant patients were excluded. In the final analysis six patients
      were excluded because of a diagnosis of bile duct obstruction but with
      unsuccessful biliary drainage that required immediate antibiotic treatment. The
      diagnosis of cholangitis was based on a rising fever, an increase in the C
      reactive protein (CRP) level, and increases in leukocyte count and liver function
      values, which were associated with bacteremia in some. The diagnosis of acute
      pancreatitis was based on clinical findings, and increases in the serum amylase
      level (>900 IU/L), CRP level, and leukocyte count with no increase in liver
      chemical values. The control group had significantly more patients with post-ERCP
      pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control
      group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to
      the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15
      patients in the control group (9%) had remarkably increased serum amylase levels
      (>900 IU/L) after ERCP, but clinical signs of acute pancreatitis with
      leukocytosis, CRP reaction, and pain developed in four of nine patients in the
      prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the
      control group (P = 0.003). In a multivariate analysis, the lack of antibiotic
      prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P =
      0.05) were independent risk factors for the development of post-ERCP
      pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the
      risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be
      routinely recommended prior to ERCP. These results suggest that bacteria could
      play a role in the pathogenesis of post-ERCP pancreatitis

PMID- 11985974
TI  - Overexpression of caspase-1 in pancreatic disorders: implications for a function
      besides apoptosis.
AB  - The caspases are known to play a crucial role in the triggering and execution of
      apoptosis in a variety of cell types. We assessed the expression of caspase-1 in
      42 pancreatic cancer tissue samples, 38 chronic pancreatitis specimens, and nine
      normal pancreatic tissues by immunohistochemistry and Western blot analysis. We
      found a clear overexpression of caspase-1 in both disorders, but differences in
      the expression patterns in distinct morphologic compartments. Pancreatic cancer
      tissue showed a clear cytoplasmatic overexpression of caspase-1 in tumor cells in
      71% of the tumors, whereas normal pancreatic tissue showed only occasional
      immunoreactivity. In chronic pancreatitis an overexpression of caspase-1 was
      found in atrophic acinar cells (89%), hyperplastic ducts (87%), and
      dedifferentiating acinar cells (84%). Although in atrophic cells a clear nuclear
      expression was found, hyperplastic ducts and dedifferentiating acinar cells
      showed clear cytoplasmic expression. Western blot analysis revealed a marked
      expression of the 45 kDa precursor of caspase-1 in pancreatic cancer and chronic
      pancreatitis (80% and 86%, respectively). Clear bands at 30 kDa, suggested to
      represent the p10-p20 heterodimer of active caspase-1, were found in 60% of the
      cancer tissue and 14% of the pancreatitis tissue specimens. Since we found a
      highly significant correlation between cytoplasm overexpression of caspase-1 in
      pancreatic cancer and overexpression of the known prognostic factors cyclin D1,
      epidermal growth factor, and epidermal growth factor receptor, it is plausible
      that caspase-1 has a yet unknown function in proliferative processes in addition
      to its well-known role in the apoptotic pathway.

PMID- 11985975
TI  - Pancreatic schwannoma: an uncommon but important entity.
AB  - The literature contains five single case reports of pancreatic schwannoma-two of
      the five occurred in patients with von Recklinghausen's disease, and three of the
      five proved malignant. Within a 3-month period, we resected benign pancreatic
      schwannomas in two patients without von Recklinghausen's disease. Both patients
      presented with pain that led to the discovery of a complex pancreatic mass on
      abdominal CT scan. Pancreatic schwannoma should be included in the differential
      diagnosis of cystic or solid pancreatic abnormalities on imaging studies.

PMID- 11985976
TI  - Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882)
      on bacterial translocation in acute pancreatitis.
AB  - Bacterial translocation is an important source of pancreas infection in acute
      pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis
      of acute pancreatitis has been proved in various studies. The aim of this study
      was to determine whether potent PAF antagonists influence bacterial translocation
      in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by
      injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats
      treated with PAF factor antagonists received intravenous injection of WEB-2170
      (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before
      induction of acute pancreatitis. Six hours after induction of acute pancreatitis,
      bacteriologic cultures and histologic scoring of tissues were performed. There
      was a statistically significant reduction in bacterial translocation to the
      mesenteric lymph nodes and liver but not to the pancreas of the rats treated with
      PAF antagonists. No significant increase in the intestinal bacterial population
      of any group was found. There were no statistical differences between the
      pancreatic histologic scores of the groups. PAF antagonists reduced bacterial
      translocation to distant sites other than the pancreas, preventing the bacterial
      dissemination that occurs in the early phase of acute pancreatitis and may have
      beneficial effects on the evolution of this disease.

PMID- 11985977
TI  - Necrotizing pancreatitis during pregnancy: a rare cause and review of the
      literature.
AB  - Acute pancreatitis is an uncommon cause of abdominal pain during pregnancy, and
      rarely progresses to the necrotizing from of the disease in this clinical
      setting. Hyperlipidemia is an infrequent cause of acute pancreatitis. Whereas
      only 100 cases of hyperlipidemia-induced necrotizing pancreatitis have been
      reported in the literature to date, all of the cases were mild in severity and
      responsive to conservative medical management. Herein we present a case of life
      threatening necrotizing pancreatitis, which developed in a hyperlipidemic
      pregnant woman and required multiple peripartum pancreatic necrosectomies.
      Additionally, we review the evaluation of pregnant patients with abdominal pain,
      the pathophysiology of hyperlipidemia-induced necrotizing pancreatitis, and the
      operative care of this challenging group of patients, revisiting an innovative
      technique for management of the retroperitoneum.

PMID- 11985978
TI  - Mediators for fat-induced ileal brake are different between stomach and proximal
      small intestine in conscious dogs.
AB  - Our aim was to determine the mechanisms by which intraileal fat alters proximal
      gastrointestinal motility--the ileal brake. Five mongrel dogs with ileal Thiry
      Vella fistulas were equipped with strain gauge force transducers on the upper gut
      to measure contractile activity. Ileal infusions of 115 mmol/L oleic acid and
      triglyceride were studied in dogs with extrinsically innervated and extrinsically
      denervated Thiry-Vella loops. Plasma concentrations of peptide YY and total
      glucagon-like immunoactivity were measured. Oleic acid but not triglyceride
      inhibited postprandial contractions in the gastric antrum in dogs with innervated
      and denervated Thiry-Vella loops. Postprandial duodenal and jejunal motility was
      inhibited by oleic acid regardless of extrinsic denervation to the loops (P
      <0.05), but triglyceride inhibited small intestinal motility only in dogs with
      innervated Thiry-Vella loops. Intraileal oleic acid but not triglyceride
      increased plasma concentrations of peptide YY and total glucagon-like
      immunoactivity in dogs with innervated and denervated Thiry-Vella loops.
      Intraileal oleic acid inhibits gastric and small intestinal motility possibly via
      increased plasma concentrations of peptide YY and enteroglucagon. Intact
      extrinsic innervation is necessary for intraileal triglyceride to inhibit small
      intestinal motility.

PMID- 11985979
TI  - Results of salvage abdominoperineal resection for recurrent anal carcinoma
      following combined chemoradiation therapy.
AB  - Combined chemotherapy and radiation therapy is the standard treatment for
      epidermoid carcinoma of the anal canal. Failures are often not associated with
      distant recurrence and are therefore potentially amenable to salvage
      abdominoperineal resection. The aim of this study was to review our experience
      with abdominoperineal resection following failure of chemoradiation therapy for
      epidermoid carcinoma of the anus. Between 1980 and 1998, 17 patients underwent
      salvage abdominoperineal resection following failure of chemoradiation therapy.
      Four patients were excluded from survival analysis because resection was
      performed with palliative intent. Survival curves were based on the method of
      Kaplan and Meier, and univariate analysis of predictive variables was performed
      using the log-rank test. Twelve patients underwent abdominoperineal resection for
      persistent disease and five patients for recurrent disease. No operative deaths
      occurred, but local complications including perineal wound infection and wound
      breakdown was seen in 8 of 17 patients and 6 of 17 patients, respectively.
      Patients undergoing omental flap reconstruction (n = 3) or no pelvic
      reconstruction (n = 5) had a higher incidence of perineal breakdown compared to
      those undergoing muscle flap reconstruction (n = 9) (P <0.05). The median follow
      up time for the patients operated on with curative intent was 53 months. The 5
      year actuarial survival was 47%. Potential prognostic factors that were not found
      to have an impact on survival included margin status of resection, sphincter
      invasion, and degree of differentiation. Only pathologic tumor size greater than
      5.0 cm (P <0.001) and age over 55 years (P <0.05) adversely affected survival.
      Selected patients with recurrent or persistent anal carcinoma following
      chemoradiation therapy can be offered salvage abdominoperineal resection. This
      operation is associated with a high incidence of local wound complications, and
      muscle flap reconstruction should be considered when possible. Prolonged survival
      can be achieved in some patients following salvage resection for epidermoid
      carcinoma of the anal canal.

PMID- 11985980
TI  - Ischemic colitis in young adults: a single-institution experience.
AB  - Ischemic colitis is not well characterized in the young adult population, despite
      its commonness in older patients. The aim of this study was to investigate the
      demographics, etiology, clinical features, and prognosis of ischemic colitis in
      young adults. We conducted a retrospective study of 39 young adults (<50 years of
      age) diagnosed with ischemic colitis over a period of 9 years (1990 to 1998). The
      mean age at diagnosis was 38 +/- 2 years (range 18 to 49 years); the female:male
      ratio was 1.8. Fifty-two percent (13 of 25) of women were using oral
      contraceptives at the time of diagnosis. Other potential associations identified
      were vascular thromboembolism (4 of 39), vasoactive drugs (4 of 39), hypovolemia
      (4 of 39), and vasculitis (2 of 39); 19 patients (49%) had no identifiable
      predisposing factors. Dominant presenting symptoms were abdominal pain (77%),
      bloody diarrhea (54%), and hematochezia (51%). Most patients were diagnosed at
      colonoscopy, and most disease was left sided. Twenty-nine patients were
      successfully managed with intravenous fluids, broad-spectrum antibiotics, and
      bowel rest; 10 patients required surgery. There was one disease-related death in
      the operative group. We found a strong female predominance and an association
      with oral contraceptive use, but almost half of the patients did not have an
      identifiable etiology. Mortality from ischemic colitis in this patient population
      is low.

PMID- 11985981
TI  - Iron deficiency suppresses ileal nitric oxide synthase activity.
AB  - Intestinal motility disorders are more common in women of childbearing age who
      are prone to iron deficiency anemia. The neurotransmitters nitric oxide (NO) and
      acetylcholine (ACh) play a key role in ileal smooth muscle relaxation and
      contraction, respectively. Iron-containing heme is known to be a cofactor for
      nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore
      we tested the hypothesis that iron deficiency would downregulate ileal NOS
      activity without affecting the ileum's response to ACh. Twelve adult female
      prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) (n = 6) or an
      iron-deficient (Fe-) (8 ppm) (n = 6) diet for 8 weeks. Ileal circular muscle
      strips were harvested to measure responses to ACh and electrical field
      stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nomega-nitro-L
      arginine (L-NNA), an NOS inhibitor, and VIP(10-28), a vasoactive intestinal
      peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC
      inhibitory responses are expressed as a percentage of optimal relaxation from
      EDTA. The excitatory response to ACh was similar in both groups (1.1 +/- 0.3
      N/cm(2) vs. 1.5 +/- 0.3 N/cm(2), P = 0.45). The inhibitory response to electrical
      field stimulation under NANC conditions was greater in the Fe+ group (34.7 +/-
      2.9%) compared to the Fe- group (23.9 +/- 3.2%; P<0.01). L-NNA eliminated the
      inhibitory response in the Fe+ group (0.02 +/- 0.02%) but not in the Fe- group
      (8.38 +/- 2.15%; P <0.01). VIP(10-28) led to greater relaxation in the Fe+
      animals (45.8 +/- 6.6%) than in the Fe- animals (23.4 +/- 5.8%; P <0.05). Both L
      NNA and VIP(10-28) had no inhibitory response (0.02 +/- 0.02%) in the Fe+
      animals, whereas the Fe- animals had some residual inhibition (2.54 +/- 1.04%; P
      <0.05). These data suggest that ileal NANC relaxation is due to NOS and that iron
      deficiency results in (1) decreased NANC relaxation, (2) a compensatory
      relaxation due to a non-NOS, non-VIP mechanism, and (3) a normal excitatory
      response. We conclude that iron deficiency suppresses ileal NOS activity.

PMID- 11985982
TI  - Quality of life following laparoscopic gastric banding in patients with morbid
      obesity.
AB  - In a prospective study of 188 patients with morbid obesity, the time-dependent
      changes in the quality of life of individual patients were analyzed following
      laparoscopic gastric banding (LGB). These 188 patients (148 females and 40 males;
      age 19 to 59 years; body mass index 33 to 72 kg/m(2)) underwent evaluation of the
      LGB according to a strict protocol that included psychological testing using
      standardized instruments, detailed medical evaluation, upper gastrointestinal
      function studies, and evaluation of quality of life using the Gastrointestinal
      Quality of Life Index (GIQLI). Following this evaluation, 73 patients (57 females
      and 16 males; age 37 years [range 19 to 59 years]; body mass index 48 kg/m(2)
      [range 37 to 72 kg/m(2)]) underwent LGB and were followed up for 2 years focusing
      on weight loss, postoperative morbidity, weight-related comorbidity, and quality
      of life. The results demonstrate that LGB is well able to allow for a significant
      loss of excess weight and a significant improvement in patients' quality of life,
      both after a rather short period of time after surgery and at a continuous rate
      throughout the follow-up. The price for this success that was found in
      approximately 90% of patients is a complication rate of 38%; 85% of these
      patients, almost one third of all patients, must undergo some type of revision
      surgery. However, once the complications are resolved, these patients achieve the
      same level of weight loss and improvement in quality of life as patients with an
      uncomplicated postoperative course.

PMID- 11985983
TI  - Functional outcome after Heller myotomy and fundoplication for achalasia.
AB  - This study aims to provide longitudinal prospective data on symptomatic outcome
      following Heller myotomy with fundoplication and to examine variables that might
      predict a poor outcome. Patients were prospectively followed by means of a
      biannual mailed questionnaire that assessed symptoms, satisfaction with the
      procedure, medication, and need for further intervention. Patients were
      classified as achieving a good or poor outcome based on predetermined criteria.
      Duration of clinical remission was determined using Kaplan-Meier curves. Between
      1992 and 1999, 62 patients with at least 12 months' follow-up were categorized as
      having either a good outcome (41 patients) or a poor outcome (21 patients). The
      cumulative probability of a good outcome at 7 years was 37%. Dysphagia
      significantly increased over the follow-up period despite initial resolution.
      Patient variables (age, sex, symptom duration, esophageal dilatation, manometric
      findings) and operative factors (myotomy length, wrap type, case number mucosal
      perforation, primary therapy) were not demonstrated to influence outcome at 3
      years. A comparison of Nissen fundoplication with partial fundoplication
      suggested increased dysphagia and chest pain in the Nissen group. Despite initial
      symptomatic relief, patients with achalasia suffer a progressive decline with
      recurrent dysphagia and regurgitation. The type of fundoplication used may
      contribute to these poor results.

PMID- 11985984
TI  - Esophageal carcinosarcoma.
AB  - Carcinosarcoma is an uncommon malignancy of the esophagus that presents as a
      bulky intraluminal polypoid lesion of the esophagus. Histologically, both
      carcinomatous and sarcomatous components are seen. Because of accelerated
      intraluminal growth, esophageal carcinosarcoma often presents relatively early.
      This report describes a 64-year-old man with carcinosarcoma who was successfully
      treated with an esophagectomy. As in typical squamous cell carcinoma, early
      detection and treatment by surgical resection are needed to produce significant
      long-term survival.

PMID- 11985985
TI  - Selective role of vagal and nonvagal innervation in initiation and coordination
      of gastric and small bowel patterns of interdigestive and postprandial motility.
AB  - Our previous studies suggested that extrinsic innervation modulates upper gut
      motility but is not requisite for cyclic interdigestive and postprandial motility
      of the stomach. However, the specific role of vagal and nonvagal extrinsic
      innervation in the initiation, coordination, and pattern of gastric motility in
      dogs after denervation of the entire upper gastrointestinal tract remains
      unclear. The aim of this study was to determine the role of vagal and nonvagal
      extrinsic innervation in control of gastric motility patterns. Mongrel dogs were
      subjected first to extrinsic denervation (in situ neural isolation) of the
      stomach, small bowel, proximal colon, liver, and pancreas but specifically
      maintaining vagal innervation to the stomach alone. After fasting and fed
      motility patterns were measured with indwelling gastric and small bowel manometry
      catheters, the dogs underwent transthoracic truncal vagotomy (completion of total
      extrinsic denervation of stomach), and motility studies were repeated. Vagal
      integrity to the stomach and pancreas was confirmed by means of a modified
      Hollander test and serum pancreatic polypeptide concentrations after the
      injection of exogenous insulin, respectively. We found that a cyclic motility
      pattern (migrating motor complex) persisted during fasting in both the stomach
      and the small bowel and that the patterns of the stomach and the duodenum
      remained temporally coordinated before and after vagotomy. However, although a
      cyclic phase III activity persisted in the stomach after vagotomy, the number of
      contractions and the motility index during phase III were decreased, and the
      duration between groupings of contractions was increased. No differences were
      noted in the duration of postprandial inhibition after feeding meals before and
      after vagotomy. These observations support our hypothesis that the vagal nerves
      are not necessary for the initiation or temporal coordination of global fasting
      or postprandial gastroduodenal motility patterns but are involved in modulating
      the pattern of contractions during gastric phase III.

PMID- 11985986
TI  - A simple scoring system for predicting bile duct stones in patients with
      cholelithiasis.
AB  - A means of accurately predicting the presence of stones in the bile duct in
      patients undergoing laparoscopic cholecystectomy for gallbladder stones is
      lacking. With the use of a three-stage analysis, a predictive score was developed
      from seven common parameters. Initially the score was formulated by using data
      from a retrospective series of patients undergoing laparoscopic cholecystectomy;
      the system was then tested prospectively over a 1-year period in patients
      undergoing laparoscopic cholecystectomy for gallbladder stones. This simple
      scoring system demonstrated an ability to predict bile duct stones with a
      sensitivity in excess of 70%. The use of such a score may allow the development
      of preoperative strategies for treating patients undergoing laparoscopic
      cholecystectomy.

PMID- 11985987
TI  - Operations for peptic ulcer disease: paradigm lost.
AB  - Over the past several decades, the pharmacologic and endoscopic treatment of
      peptic ulcer disease (PUD) has dramatically improved. To determine the effects of
      these and other changes on the operative management of PUD, we reviewed our
      surgical experience with gastroduodenal ulcers over the past 20 years. A
      computerized surgical database was used to analyze the frequencies of all
      operations for PUD performed in two training hospitals during four consecutive 5
      year intervals beginning in 1980. Operative rates for both intractable and
      complicated PUD were compared with those for other general surgical procedures
      and operations for gastric malignancy. In the first 5-year period (1980 to 1984),
      a yearly average of 70 upper gastrointestinal operations were performed. This
      experience included 36 operations for intractability, 15 for hemorrhage, 12 for
      perforation, and seven for obstruction. During the same time span, 13 resections
      were performed annually for gastric malignancy. By the most recent 5-year
      interval (1994 to 1999), the total number of upper gastrointestinal operations
      had declined by 80% (14 cases), although the number of operations for gastric
      cancer had changed only slightly. Operations decreased most markedly for patients
      with intractability, but the prevalence of operations for bleeding, obstruction,
      and perforation was also decreased. We conclude that improved pharmacologic and
      endoscopic approaches have progressively curtailed the use of operative therapy
      for PUD. Elective surgery is now rarely indicated, and emergency operations are
      much less common. This changed paradigm poses new challenges for training and
      suggests different approaches for practice.

PMID- 11985990
TI  - Outcome of laparoscopic anterior 180-degree partial fundoplication for
      gastroesophageal reflux disease.

PMID- 11985993
TI  - Management of patients with gastroesophageal reflux disease and esophageal or
      gastric dysmotility.

PMID- 11985994
TI  - Approach and management of patients with recurrent gastroesophageal reflux
      disease.

PMID- 11985995
TI  - The short esophagus-recognition and management.

PMID- 11985996
TI  - Laparoscopic fundoplication for symptomatic but physiologic gastroesophageal
      reflux.
AB  - Esophageal pH monitoring identifies some patients who have physiologic amounts of
      esophageal acid exposure but have a strong correlation between symptoms of
      esophageal reflux events. These patients with symptomatic physiologic reflux
      probably have enhanced sensory perception of reflux events and may be difficult
      to control with acid-suppressive therapy. Little is known about the role of
      fundoplication in such patients. Patients with no endoscopic evidence of
      gastroesophageal reflux disease and a normal 24-hour pH composite score (<22.4 in
      our laboratory), but a symptom index (SI = number of symptoms with pH <4/total
      number of symptoms) greater than 50% were offered laparoscopic fundoplication if
      acid-suppressive therapy was unsatisfactory. This group comprised 18 (4%) of 459
      patients undergoing fundoplication at our institution. Heartburn, dysphagia, and
      reflux symptoms were scored on a scale of 0 to 10 with patients on and off
      medicine preoperatively, and at a mean of 7.2 months (range 1 to 32 months)
      postoperatively. The 18 patients with symptomatic physiologic reflux (6 males and
      12 females) had heartburn as a major complaint. Preoperative response to proton
      pump inhibitors for heartburn was 72% and for all symptoms was 60%. The group had
      a mean pH composite score of 14 (range 4 to 22). The symptom used to calculate
      the symptom index was heartburn in 12 patients, regurgitation in three, chest
      pain in two, and cough in one. An average of 18 symptoms (range 2 to 56) were
      recorded. The mean symptom index was 82% (range 50% to 100%). A Nissen
      fundoplication was performed in nine patients and a Toupet fundoplication in
      nine. Surgery was successful (>90%) in alleviating reflux symptoms in 14 patients
      and partially successful (>75%) in three of the remaining four patients. Gas
      bloat and dysphagia were seen in one patient each. Fundoplication is effective at
      relieving reflux symptoms in carefully selected patients with symptomatic
      physiologic reflux, with minimal side effects.

PMID- 11985997
TI  - Hepatitis B or C virus serology as a prognostic factor in patients with
      hepatocellular carcinoma.
AB  - It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is
      a prognostic factor for hepatocellular carcinoma. We performed this study to
      determine if chronic HBV or HCV infection had any impact on postresection
      survival or affected patterns of failure. The records of 77 patients undergoing
      surgical resection for hepatocellular carcinoma between January 1990 and December
      1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients
      (23%) had HBV infection, and 15 patients (20%) had negative serology. There were
      no differences in age, sex, or tumor size among the groups, and all patients had
      margin-negative resections. There was a significantly higher incidence of
      satellitosis and vascular invasion in patients with HCV infection (32% and 41%
      respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a
      significantly decreased local disease-free survival (LDFS) was seen in HBV
      positive (5-year LDFS 26%) or HCV-positive (5-year LDFS 38%) patients compared to
      those with negative serology (5-year LDFS 79%; P <0.05). There was also a trend
      toward a decreased overall survival in patients with positive hepatitis serology
      compared to patients with negative serology (37% vs. 79%; P = 0.12). Univariate
      analysis revealed that only satellitosis was related to local recurrence and
      overall survival. Patients with positive serology for hepatitis B or C undergoing
      resection for hepatocellular carcinoma have a trend toward worse overall
      prognosis and a significantly decreased LDFS when compared to patients with
      negative serology.

PMID- 11985998
TI  - Ultrasound-guided radiofrequency thermal ablation of liver tumors: percutaneous,
      laparoscopic, and open surgical approaches.
AB  - Only 10% to 20% of patients with primary and colorectal metastatic liver tumors
      are candidates for curative surgical resection. Even after curative treatment,
      tumors recur commonly in the liver. As a less invasive therapy, radiofrequency
      thermal ablation (RFA) of primary, metastatic, and recurrent liver tumors was
      performed under percutaneous, laparoscopic, or open intraoperative ultrasound
      guidance. The safety and local control efficacy of RFA were investigated. RFA was
      performed mostly in patients with unresectable hepatomas or metastatic liver
      tumors. Patients with large tumors, major vessel or bile duct invasion, limited
      extrahepatic metastases, or liver dysfunction were not excluded. An RFA system
      with a 15-gauge electrode-cannula with four-pronged retractable needles was used.
      All patients were followed for more than 8 months to assess morbidity and
      mortality, and to determine tumor recurrence. Sixty RFA operations were performed
      in 46 patients: 11 patients underwent repeat RFA once or twice. A total of 204
      tumors were treated: 70 hepatomas and 134 metastatic tumors. Tumor size ranged
      from 5 mm to 180 mm (mean 36 mm). RFA was performed in 29 operations for 81
      tumors percutaneously, in seven operations for 14 tumors laparoscopically, and in
      24 operations for 109 tumors by open surgery. Combined colorectal resection was
      carried out in five operations and combined hepatic resection was carried out in
      three operations. There was one death (1.7%) from liver failure, and there were
      three major complications (5%): one case of bile leakage and two biliary
      strictures due to thermal injury. There were no intra-abdominal infectious or
      bleeding complications. The length of hospital stay ranged from 0 to 2, 1 to 3,
      and 4 to 7 days for percutaneous, laparoscopic, and open surgical RFA,
      respectively. During a mean follow-up period of 20.5 months, local tumor
      recurrence at the RFA site was diagnosed in 18 (8.8%) of 204 tumors. The risk
      factors for local recurrence included large tumor size and major vessel invasion:
      recurrence rates for tumors less than 4 cm, 4 to 10 cm, and greater than 10 cm,
      and for those with vessel invasion were 3.3%, 14.7%, 50%, and 47.8%,
      respectively. Ten of 18 tumors recurring locally were retreated by RFA, and eight
      of them showed no further recurrence. Ultrasound-guided RFA is a relatively safe,
      well-tolerated, and versatile treatment option that offers excellent local
      control of primary and metastatic liver tumors. The appropriate use of
      percutaneous, laparoscopic, and open surgical RFA is beneficial in the management
      of patients with liver tumors in a variety of situations.

PMID- 11985999
TI  - Alterations in intrahepatic hemodynamics of the harvested porcine liver.
AB  - Hemodynamic properties of a donor liver, during initial reperfusion, are
      associated with the degree of graft preservation injury and have been proposed to
      correlate with subsequent markers of liver function. In the present study,
      hepatic hemodynamics, that is, portal venous pressure, hepatic vascular
      resistance, and compliance (vascular distensibility), were characterized (1) in
      situ before porcine livers were manipulated, (2) after these same livers were
      isolated and perfused within a bypass circuit, and (3) on reperfusion after 2
      hours of cold ischemia. Hepatic vascular resistance was determined in each of
      these three states from the portal vein pressure response to differing hepatic
      blood flows. In addition, the response of the same livers to norepinephrine and
      nitroprusside was evaluated in each condition. In the in situ and isolated
      perfused liver, portal venous pressure increased only modestly despite doubling
      of hepatic flows. After cold ischemia, the pressure response to higher flows was
      significantly greater and much less of a reduction in hepatic vascular resistance
      was noted than in studies prior to cold ischemia. Unlike livers prior to cold
      ischemia, the pressure response to norepinephrine was attenuated following cold
      ischemia. The response to nitroprusside, however, remained intact reducing the
      portal pressure to that of in situ livers. Therefore the portal hypertension that
      follows cold ischemia appears to be largely provoked by the preservation injury
      and not by surgical manipulation or the bypass circuit. This increment in portal
      pressure is responsive to a nitric oxide donor.

PMID- 11986000
TI  - Diminished morbidity and mortality in portal hypertension surgery: relocation in
      the therapeutic armamentarium.
AB  - Although several effective therapeutic options are available for bleeding from
      portal hypertension, surgery has a well-defined role in the management of
      patients with good liver function who are electively operated. The aim of this
      investigation was to evaluate the operative mortality and morbidity of portal
      blood flow-preserving procedures in a highly select patient population. The
      records of 148 patients operated on between 1996 and 2000 using one of two
      techniques (selective shunts or a Sugiura-Futagawa operation [complete
      portoazygos disconnection]) were analyzed with particular attention to operative
      mortality, postoperative rebleeding, and encephalopathy. Survival was calculated
      according to the Kaplan-Meier method. Sixty-one patients had distal splenorenal
      shunts placed, and 87 patients had a devascularization procedure. Operative
      mortality for the group as a whole was 1.2%. In the group with selective shunts,
      the rebleeding rate was 4.9%, the encephalopathy rate was 9.8%, and the shunt
      obstruction rate was 1.6%. Survival at 24 months was 94% and at 48 months was
      92%. In those undergoing devascularization, the encephalopathy rate was 5% and
      the rebleeding rate was 14%. Survival at 24 months was 90% and at 48 months was
      86%. Portal blood flow-preserving procedures have very low morbidity and
      mortality rates at specialized centers. In addition, a low rebleeding rate is
      associated with a good quality of life. Low-risk patients with bleeding portal
      hypertension should be considered for surgical treatment.

PMID- 11986001
TI  - Preoperative intraluminal application of capsaicin increases postoperative
      gastric and colonic motility in rats.
AB  - In a model to investigate postoperative gastrointestinal motility with strain
      gauge transducers in awake rats, we tested the effects of intraluminal capsaicin
      infusion into the cecum 2 days or 14 days prior to abdominal surgery. Acute
      infusion of capsaicin into the cecum for 30 minutes increased the gastric, small
      intestinal, and colonic motility index by up to 115%, 34%, and 59%, respectively,
      compared to vehicle infusion. Intraluminal capsaicin infusion 2 days prior to
      abdominal surgery significantly increased the intraoperative gastric and colonic
      motility index by 166% and 100%, respectively, compared to vehicle, but had no
      effect on small intestinal motility. The postoperative decrease in gastric or
      colonic motility was completely prevented by capsaicin pretreatment, representing
      a 73% and a 72% increase in the motility index during the first postoperative
      hour and a 40% and a 29% increase in the motility index during the second
      postoperative hour compared to vehicle, whereas the postoperative decrease in
      small intestinal motility was not altered by capsaicin pretreatment. In contrast,
      intraluminal capsaicin infusion 14 days prior to abdominal surgery had no effect
      on postoperative inhibition of gastrointestinal motility. Our results suggest
      that capsaicin-sensitive visceral afferent C-fibers, presumably of the submucosa,
      play an important role in mediating postoperative ileus. Intraluminal capsaicin
      does probably ablate these nerve fibers temporarily, with no systemic side
      effects observed with the use of the tail flick test as a measure of skin
      nociception.

PMID- 11986002
TI  - Myenteric plexus in spastic motility disorders.
AB  - Previous studies have often revealed an absence or reduction of ganglia in
      Auerbach's plexus in many patients with achalasia, which has been postulated to
      be related to the elevated lower esophageal sphincter pressure in these patients.
      We undertook a prospective study to determine whether microscopic changes were
      present in the myenteric plexus of patients with hypertensive lower esophageal
      sphincter, nutcracker esophagus, and diffuse esophageal spasm and if there was a
      correlation with lower esophageal sphincter pressure. Nine patients (3 men and 6
      women; ages 49 to 72 years, mean 58 years) underwent a laparoscopic
      esophagomyotomy with fundoplication for symptomatic spastic motility disorder. A
      10 mm x 5 mm segment of esophageal muscle was removed from the border of the
      myotomy incision, fixed in formalin, and examined under light microscopy for the
      presence or absence of ganglia and inflammation. Correlation between the presence
      of ganglia and lower esophageal sphincter pressure was tested by Pearson's
      bivariant correlation. Manometry revealed three patients with hypertensive lower
      esophageal sphincter, four patients with nutcracker esophagus, and two patients
      with diffuse esophageal spasm. All three patients with a hypertensive lower
      esophageal sphincter revealed an absence of ganglia, whereas the six patients
      with nutcracker esophagus and diffuse esophageal spasm exhibited ganglia despite
      an elevated lower esophageal sphincter pressure in four. Hypertensive lower
      esophageal sphincter resembled achalasia in its absence of ganglia in Auerbach's
      plexus, whereas nutcracker esophagus and diffuse esophageal spasm exhibited
      ganglia. There was no significant correlation in our series between the presence
      of ganglia and an elevated lower esophageal sphincter pressure in spastic
      motility disorders.

PMID- 11986004
TI  - Long- or short-limb gastric bypass?
AB  - The aim of this study was to determine whether longer limb length improved
      results of gastric bypass in patients who were morbidly obese (body mass index
      <50 kg/m(2)) or superobese (body mass index >50 kg/m(2). A total of 242 patients
      were followed for a mean of 5.5 years. The standard operation was a Roux-en-Y
      gastric bypass with a 40 cm Roux limb and a 10 cm afferent limb. The long-limb
      operation had a 100 cm Roux limb and a 100 cm afferent limb. Morbidly obese
      patients did not benefit from a long-limb bypass. The final body mass index was
      28.6 +/- 4.7 kg/m(2) in the short-limb group and 28.5 +/- 3.8 kg/m(2) in the long
      limb group. The superobese patients did benefit from a long-limb bypass. Final
      body mass index was 35.8 +/- 6.7 kg/m(2) in the short-limb patients and 32.7 +/-
      5.1 in the long-limb patients (P = 0.049). A subgroup of 20 patients, all of whom
      had a body mass index greater than 60 kg/m(2), benefited the most from long-limb
      bypass. No macronutritional side effects unique to the long-limb bypass were
      encountered.

PMID- 11986003
TI  - Ileal absorptive adaptation to jejunal resection and extrinsic denervation:
      implications for living-related small bowel transplantation.
AB  - Net absorption of water, electrolytes, and simple nutrients decreases early after
      jejunoileal autotransplantation (extrinsic denervation) in a canine model but
      recovers toward normal by 8 weeks. However, the ability of the extrinsically
      denervated ileum to adapt after total jejunectomy, which would be relevant as a
      model of segmental small bowel transplantation, remains unknown. Two groups of
      five dogs each were studied before and 2 weeks and 12 weeks after 50% proximal
      enterectomy. A control group remained neurally intact, whereas the other group
      underwent extrinsic denervation (Ext Den) of the remaining ileum. Using a
      perfusion technique, net absorption of water, electrolytes, and five simple
      nutrients (glucose, arginine, glutamine, and oleic and taurocholic acids) was
      measured at the three time points. Ileal morphometry was also evaluated. All dogs
      developed diarrhea, which resolved by 12 weeks in all but two of the Ext Den
      dogs. Weight in both groups was decreased at 2 weeks (P <0.05), returned to
      normal at 12 weeks in control dogs, but remained low in Ext Den dogs (P <0.05).
      Maximal weight loss was greater in the Ext Den group (P <0.05). No consistent or
      important differences in net absorptive fluxes of water, electrolytes, or simple
      nutrients were noted either within or between groups at any time point. Villous
      height, crypt depth, and longitudinal muscle width increased significantly at 12
      weeks after jejunectomy in the Ext Den dogs, but not in the control dogs (P
      <0.05). Extrinsic denervation of the ileum results in persistent weight loss
      after proximal 50% enterectomy. Despite diarrhea, only minor changes in
      electrolyte absorption occur, and ileal net absorption of simple nutrients
      remains unaffected. The ileum of extrinsically denervated dogs undergoes a more
      prominent morphometric adaptation after jejunectomy. Extrinsic denervation
      necessitated by small bowel transplantation, independent of immune effects, does
      not appear to suppress the ileal adaptive response to maintain net absorption of
      water, electrolytes, and simple nutrients.

PMID- 11986005
TI  - Effects on endogenous acetaldehyde production by disulfiram and ethanol feeding
      on rat pancreas.
AB  - Exogenous acetaldehyde infusion can induce pancreatitis-like injury of the
      pancreas in some isolated pancreas models, whereas in vivo such treatment has
      failed to induce pancreatitis. In vivo exogenous acetaldehyde may not be
      effective because it is rapidly metabolized. The aim of this study was to
      investigate whether endogenous acetaldehyde accumulates in the pancreas after
      ethanol feeding when acetaldehyde metabolism is blocked by disulfiram, and
      whether this treatment can induce pancreatitis-like injury in the rat. The liver
      was studied for comparison. In part I of the experiment, adult male Wistar rats
      were given water (n = 24), ethanol (n = 24), disulfiram (n = 24), and ethanol
      plus disulfiram for 1 week (n = 24) or 3 weeks (n = 24) and for 3 weeks with (n =
      6) and without (n = 6) hypovolemia. In part II of the experiment, rats were given
      water (n = 6), ethanol (n = 6), and high-dose disulfiram (n = 6) and ethanol plus
      high-dose disulfiram (n = 6). Ethanol and acetaldehyde concentrations in blood,
      liver, and pancreas were measured. Animal behavior was monitored, and weight
      changes, plasma amylase activity, water content, and histomorphology of the
      pancreas and liver were studied without knowing the group. No increases in plasma
      amylase activity and no histomorphologic changes in the pancreas were observed
      under light or electron microscopy in part I of the experiment. In part II,
      treatment with ethanol induced acetaldehyde accumulation in the liver (33.6 +/-
      2.6 micromol/L), but to a lesser degree in the blood (9.6 +/- micromol/L) and
      pancreas (5.0 +/-.2 micromol/L). Ethanol plus disulfiram induced marked
      accumulation of acetaldehyde in the liver (83.2 +/- 15.9 micromol/L), blood
      (280.0 +/- 47.4 micromol/L), and pancreas (43.6 +/- 4.7 micromol/L). When tissue
      acetaldehyde levels reached 30 to 40 micromol/L, we found a decrease in zymogen
      granules along with formation of small intracytoplasmic vacuolizations in the
      acinar cells and accumulation of lipid droplets in the hepatocytes, whereas
      physiologic signs of pancreatitis (hyperamylasemia, edema) or increases in liver
      enzymes did not develop. High levels of acetaldehyde accumulate in the liver and
      pancreas with the treatment described. Although this was accompanied by lipid
      degeneration of the hepatocytes and some subcellular changes in the acinar cells,
      physiologic signs of pancreatitis did not develop. Thus acetaldehyde accumulation
      alone, or in combination with hypovolemia, is not responsible for the induction
      of acute pancreatitis.

PMID- 11986006
TI  - Bile acid absorption after near-total proctocolectomy in dogs: ileal pouch vs.
      jejunal pouch-distal rectal anastomosis.
AB  - Bile acid malabsorption is often present in patients after near-total
      proctocolectomy and ileal pouch-anal canal anastomosis, suggesting ileal
      dysfunction. Experiments were performed in dogs to compare bile acid absorption
      after a modified procedure, in which a jejunal pouch was interposed between the
      terminal ileum and the distal rectum, with that after a conventional ileal pouch
      operation. Fecal bile acid output (equivalent to hepatic bile acid biosynthesis)
      and composition were determined by gas chromatography/mass spectrometry in five
      jejunal pouch dogs and in five ileal pouch dogs more than 6 months after
      operation. Fecal bile acid output in the jejunal pouch dogs (mean +/- standard
      deviation) was 215 +/- 59 mg/day (10.1 +/- 2.7 mg/kg-day), a value similar to
      that obtained in the ileal pouch dogs (261 +/- 46 mg/day [12.8 +/- 3.1 mg/kg
      day]; P >0.05). These values were also similar to those reported by others for
      healthy unoperated dogs, indicating that increased bile acid biosynthesis
      occurring in response to bile acid malabsorption was not present. Fecal bile
      acids in pouch dogs were completely deconjugated and extensively 7-dehydroxylated
      (jejunal pouch = 90.4% dehydroxylated; ileal pouch = 88.6% +/- 6.6%
      dehydroxylated) and consisted predominantly of deoxycholic acid derivatives. We
      conclude that when either a jejunal pouch or an ileal pouch is used as a rectal
      substitute in dogs, an anaerobic pouch flora develops that efficiently
      deconjugates and dehydroxylates bile acids, rendering them membrane permeable.
      The resultant passive absorption of unconjugated bile acids appears to compensate
      for any loss of active ileal absorption of conjugated bile acids, and bile acid
      malabsorption does not occur.

PMID- 11986007
TI  - Hypoosmotic stress stimulates growth in HepG2 cells via protein kinase B
      dependent activation of activator protein-1.
AB  - Although hypoosmotic stress-induced cell swelling activates phosphatidylinositol
      3-kinase, its impact on the downstream signal protein kinase B and cell growth is
      unknown. Activator protein-1 is in part phosphatidylinositol-3-kinase dependent,
      and is important in proliferation. We hypothesized that cell swelling modulates
      proliferation in HepG2 cells via the protein kinase B-dependent activation of
      activator protein-1. HepG2 cells pretreated with or without LY294002 were exposed
      for up to 30 minutes to hypoosmotic medium (160 mOsm/L). Tumor necrosis factor
      alpha (1.4 nmol/L) or normoosmolar medium (270 mOsm/L) served as positive and
      negative controls, respectively. Western immunoblots measured cytoplasmic
      phosphorylated and total protein kinase B. Electromobility shift assays measured
      nuclear activator protein-1. Methylene blue assays measured cell proliferation at
      24, 48, and 72 hours after stimulation. Hypoosmotic stress phosphorylated protein
      kinase B by 10 minutes. Subsequently, hypoosmotic exposure stimulated activator
      protein-1 by 30 minutes. Pulse exposure to hypoosmotic stress potentiated HepG2
      proliferation by 72 hours as compared to both negative controls and LY-inhibited
      cells (n = 4 per group, P = 0.009 and P = 0.004, respectively; P <0.001 analysis
      of variance. All three activation events were abolished with LY294002
      pretreatment. In HepG2 cells, hypoosmotic stress-induced swelling stimulates
      proliferation via protein kinase B-mediated activation of activator protein-1.
      These data delineate a possible mechanism linking changes in cell volume to
      growth in human liver cancer.

PMID- 11986009
TI  - Letter to the editors.

PMID- 11986011
TI  - Absence of gastroesophageal reflux disease in a majority of patients taking acid
      suppression medications after Nissen fundoplication.
AB  - Recent studies have shown that many patients use acid suppression medications
      after antireflux surgery. The aim of this study was to determine the frequency of
      gastroesophageal reflux disease in a cohort of surgically treated patients with
      postoperative symptoms and a high prevalence of acid suppression medication use.
      The study group consisted of 86 patients who had symptoms following Nissen
      fundoplication that were sufficient to merit evaluation with 24-hour distal
      esophageal pH monitoring. All completed a detailed symptom questionnaire. The
      mean postoperative follow-up period was 28 months (median 18 months). Thirty
      seven patients (43%) were taking acid suppression medications after
      fundoplication. Only 23% (20 of 86) of all the patients and only 24% (9 of 37) of
      those taking acid suppression medications had abnormal esophageal acid exposure
      on the 24-hour pH study. Heartburn and regurgitation were the only symptoms that
      were significantly associated with an abnormal pH study. Endoscopic assessment of
      the fundoplication was the most significant factor associated with an abnormal pH
      study. Multivariable logistic regression analysis showed that patients with a
      disrupted, abnormally positioned fundoplication had a 52.6 times increased risk
      of abnormal esophageal acid exposure. Most patients who use acid suppression
      medications after antireflux surgery do not have abnormal esophageal acid
      exposure, and the use of these medications is thus often inappropriate. Because
      of the limited predictive power of symptoms, objective evidence of reflux disease
      should be obtained before prescribing acid suppression medication for patients
      who have undergone antireflux surgery.

PMID- 11986008
TI  - The gut and food intake: an update for surgeons.
AB  - Food intake is the simplest and most obvious measure of gastrointestinal
      function, yet it rarely receives more than cursory attention from surgeons. In
      this review we cover recent findings on relationships between gut function and
      appetite regulation mediated via neuropeptides influenced by afferent and
      efferent vagal activity. Evidence from the new discipline known as
      neurogastroenterology elucidates gastric and intestinal signals involved in the
      elicitation of hunger, satiety, and aversion. Discovery of the adipose-tissue
      derived hormone, leptin, has energized the field of metabolism spawning
      increasing numbers of publications related to interactions between leptin and
      insulin release and glucose disposal, as well as appetitive behavior. Peptides
      such as cholecystokinin (CCK), the proglucagon-derived peptides, glucagon-like
      peptides 1 and 2 (GLP-1 and GLP-2), and the recently identified powerful intake
      stimulating molecule, orexin, are examples of potential targets for drug
      development and studies of surgical pathophysiology. A major conclusion of this
      work is that the considerable redundancy and overlap between mediators of caloric
      intake subserving survival of the species, while beneficial after foregut
      surgery, contribute to the complexity of treating the global epidemic of obesity.
      Possibly knowledge derived from basic research in neurogastroenterology can
      translate into advances in surgical treatment of obesity.

PMID- 11986012
TI  - Computer-enhanced vs. standard laparoscopic antireflux surgery.
AB  - Computer-assisted telesurgical devices have recently been approved in the United
      States for general surgery. To determine the safety and efficacy of these
      procedures, we performed a prospective trial of computer-enhanced "robotic"
      fundoplication compared to standard laparoscopic control procedures. Consecutive
      patients undergoing surgical treatment for gastroesophageal reflux were included.
      The operating surgeon worked at a console using a three-dimensional image and
      manipulated hand controls. Operative times, complications, and length of hospital
      stay were recorded. A standardized questionnaire was administered to evaluate
      symptoms. Twenty patients were entered into each group. There were no differences
      in age, preoperative weight, or sex. Operative times were significantly longer in
      the robot group (97 vs. 141 minutes). There were no complications and most
      patients went home the first postoperative day. At follow-up, symptoms were
      similar in both groups; however, there was a significant difference in the number
      of patients taking antisecretory medication--none in the robotic group but six in
      the laparoscopic group reported regular use. Computer-assisted laparoscopic
      antireflux surgery is safe. However, operative times are longer, with little
      difference in outcomes. At the current level of technology and experience,
      robotic antireflux surgery appears to offer little advantage over standard
      laparoscopic approaches.

PMID- 11986013
TI  - Laparoscopic antireflux surgery and its effect on cough in patients with
      gastroesophageal reflux disease.
AB  - In addition to heartburn and regurgitation, cough is a frequent nonspecific
      complaint of patients with gastroesophageal reflux disease. The incidence of
      alternative etiologies for patients with chronic cough who are undergoing
      antireflux surgery is not known. To determine this, and the response of chronic
      cough to fundoplication, we performed a retrospective review of 129 patients with
      proven gastroesophageal reflux referred for surgical therapy. Chronic cough was
      present in 37 (29%) preoperatively. No differences were found in age, sex, or
      preoperative manometric findings between those with and without chronic cough.
      Patients with cough had a higher number of lower esophageal reflux events on
      preoperative 24-hour pH testing, and were more likely to have persistent
      dysphagia after surgery. Fifty-nine percent of patients with cough had an
      alternative etiology for cough, compared to 36% of those without cough. Of the
      common alternative etiologies, only a history of postnasal drip occurred more
      frequently in those with cough. Complete resolution of cough occurred in 24
      patients (64%), with another 10 (27%) reporting significant improvement. The
      average cough score improved significantly regardless of which coexisting
      etiology the patients may have had. Additionally, heartburn and regurgitation
      were improved in 94% of all patients.

PMID- 11986014
TI  - Physiologic mechanism and preoperative prediction of new-onset dysphagia after
      laparoscopic Nissen fundoplication.
AB  - The aim of this study was to determine whether preoperative physiologic factors
      can account for and be used to predict the development of postoperative dysphagia
      after laparoscopic Nissen fundoplication. One hundred sixty-three patients with
      gastroesophageal reflux disease underwent laparoscopic Nissen fundoplication with
      a median follow-up of 14 months (range 6 to 81 months). Preoperative dysphagia
      was present in 37% (60 of 163) and was relieved in all but five patients (92%).
      Female sex (P = 0.01) and the presence of a stricture (P = 0.02) were the only
      preoperative variables associated with the presence of preoperative dysphagia.
      Eight percent (8 of 103) of patients without preoperative dysphagia developed new
      onset dysphagia, and of these 63% (5 of 8) had a normal lower esophageal
      sphincter (LES) (pressure >6 mm Hg; length >2 cm; abdominal length >1 cm). New
      onset dysphagia was significantly more common in patients with a normal LES (22%
      [5 of 23] vs. 4% [3 of 80], P = 001). Patients with a normal LES had almost a
      sixfold increase in the risk of developing dysphagia as those with an abnormal
      LES (relative risk = 5.8). Only a preoperative normal LES (P = 0.02) or mean LES
      pressures (P = 0.04) were positively associated with the development of
      postoperative dysphagia. The severity of this dysphagia also showed a strong
      positive trend of increasing with mean preoperative LES pressures (P = 0.07).
      Finally, preoperative LES pressure significantly correlated with postoperative
      LES pressure (r = 0.48, P = 0.01) and with mean residual LES (nadir) pressure (r
      = 0.33, P = 0.05) offering insight into the mechanism of this dysphagia. In
      conclusion, preoperative LES parameters play a role in the development of
      dysphagia after laparoscopic Nissen fundoplication. Patients with a normal LES or
      high mean LES pressures are at increased risk for developing this complication
      and should be informed of this before laparoscopic Nissen fundoplication.

PMID- 11986015
TI  - Long-term survival after esophagectomy for Barrett's adenocarcinoma in
      endoscopically surveyed and nonsurveyed patients.
AB  - There is growing controversy over the cost-effectiveness of surveillance
      endoscopy for patients with Barrett's esophagus. A retrospective review was
      performed of 80 patients who underwent resection for Barrett's adenocarcinoma to
      assess the influence of endoscopic surveillance on long-term survival. Twelve
      patients initially were diagnosed with benign Barrett's esophagus and were
      followed with endoscopic surveillance. The remaining 68 patients had the
      diagnosis of Barrett's esophagus made at the time of their cancer diagnosis or
      resection. Patients in surveillance programs were younger (53 vs. 64 years; P =
      0.008), had better performance status (8.9 vs. 8.2; P = 0.04), had less weight
      loss (0.3 vs. 5.5 kg; P < 0.001), had a similar incidence of gastroesophageal
      reflux disease symptoms (75% vs. 60%), and were less likely to undergo
      preoperative chemotherapy and/or radiation therapy (8% vs. 28%). Pathologic stage
      was 0 or I in 9 (75%) of 12 patients in the surveillance group compared to 12
      (18%) of 68 of those in the no surveillance group (P < 0.001). Median survival
      for patients in the surveillance group was 107 months compared to 12 months for
      those in the no surveillance group (P < 0.001). Stratifying for stage,
      surveillance (hazard ratio = 3.05; confidence interval = 1.09 to 8.57; P = 0.034)
      was the only predictor of survival. Surveillance endoscopy permits early
      diagnosis of adenocarcinoma in patients with Barrett's esophagus and contributes
      substantially to long-term survival.

PMID- 11986016
TI  - Novel nuclear shuttle peptide to increase transfection efficiency in esophageal
      mucosal cells.
AB  - The major barrier to successful transfection appears to be passage of the DNA
      plasmid from the cytoplasm into the cell nucleus. The M9 nuclear localization
      peptide, a fragment of the naturally occurring heterogeneous nuclear
      ribonucleoprotein A1, which serves to shuttle messenger RNA across the nuclear
      membrane, has been proposed as a tool for enhancing transfection efficiency. We
      tested three different reporter plasmids to assess the ability of M9 to improve
      transfection efficiency in esophageal mucosal cells. The effect of M9 on the
      intracellular movement of plasmid was also assessed using fluorescent microscopy
      to trace rhodamine-labeled plasmid. The M9 nuclear shuttle peptide consistently
      increased the transfection efficiency. When transfection was carried out with
      specific plasmids, beta-galactosidase enzyme activity, keratinocyte growth factor
      1 growth factor levels, and the number of transfected cells expressing growth
      factor peptides were progressively increased with increasing M9 to plasmid
      ratios. Fluorescent microscopy demonstrated that the M9 shuttle allowed rhodamine
      tagged plasmid to gain access to the nucleus, while it was located exclusively in
      the cytoplasm without the peptide. The M9 shuttle peptide increases transfection
      efficiency in esophageal mucosal cells, and therefore may have a useful role in
      gene therapy applications involving the esophagus.

PMID- 11986017
TI  - Does mechanical massage of the abdominal wall after colectomy reduce
      postoperative pain and shorten the duration of ileus? Results of a randomized
      study.
AB  - The aim of this study was to determine the effectiveness of mechanical abdominal
      massage on postoperative pain and ileus after colectomy. We hypothesized that
      parietal abdominal stimulation could counteract induced pain and postoperative
      ileus, through common spinal-sensitive pathways, with nociceptive visceral
      messages. After preoperative randomization, 25 patients (age 52 +/- 5 years)
      underwent active mechanical massage by intermittent negative pressure on the
      abdominal wall resulting in aspiration (Cellu M50 device, LPG, Valence, France),
      and 25 patients (age 60 +/- 6 years) did not receive active mechanical massage
      (placebo group). Massage sessions began the first day after colectomy and were
      performed daily until the seventh postoperative day. In the active-massage group,
      amplitude and frequency were used, which have been shown to be effective in
      reducing muscular pain, whereas in the placebo group, ineffective parameters were
      used. Visual analogue scale (VAS) pain scores, doses of analgesics
      (propacetamol), and delay between surgery and the time to first passage of flatus
      were assessed. Types and dosages of the anesthetic drugs and the duration of the
      surgical procedure did not differ between groups. From the second and third
      postoperative days, respectively, VAS pain scores (P < 0.001) and doses of
      analgesics (P < 0.05) were significantly lower in patients receiving active
      massage compared to the placebo group. Time to first passage of flatus was also
      significantly shorter in the active-massage group (1.8 +/- 0.3 days vs. 3.6 +/-
      0.4 days, P < 0.01). No adverse effects were observed. These results suggest that
      mechanical massage of the abdominal wall may decrease postoperative pain and
      ileus after colectomy.

PMID- 11986018
TI  - Should suspected early gallbladder cancer be treated laparoscopically?
AB  - Early gallbladder cancer (EGC), defined as T1 and T2 disease, is frequently
      curable when completely excised without bile spillage. The objective of the
      present study was to determine what effect initial laparoscopic cholecystectomy
      has on outcome in patients with EGC. Of 89 patients referred to our institution
      with gallbladder cancer over an 11-year period, 26 had undergone initial
      laparoscopic cholecystectomy. Sixteen of the 26 patients had T1 or T2 disease and
      are the subjects of this report. These patients were reviewed retrospectively to
      assess preoperative diagnosis, intraoperative bile spillage, and outcome
      (recurrence and survival). In addition, the Western literature was reviewed to
      determine the impact of initial laparoscopic cholecystectomy on recurrence and
      survival of patients with EGC. Six patients had a preoperative ultrasound
      consistent with a mass in the gallbladder wall. Seven (44%) had documented bile
      spillage during the laparoscopic cholecystectomy. T stage based on the
      laparoscopic cholecystectomy was T1 (n = 1) and T2 (n = 15). Twelve patients
      underwent reexploration of whom seven underwent further radical excision
      (gallbladder liver bed resection and extensive lymphadenectomy). After a mean
      follow-up of 20.1 months (range 4 to 39 months), 69% of patients have had a
      recurrence or died. Three patients had a port-site recurrence. Five (71%) of
      seven patients with bile spillage at laparoscopic cholecystectomy have had a
      recurrence or died of disease. A review of the Western literature on EGC
      initially removed by laparoscopic cholecystectomy (including the present series)
      yielded 21 patients with T1 and 42 patients with T2 disease. One-year Kaplan
      Meier survival (T1 = 89%, T2 = 71%) and 3-year Kaplan-Meier survival (T1 = 47%,
      T2 = 40%) of these patients is worse than prior reports for open cholecystectomy.
      An initial laparoscopic cholecystectomy with its potential for bile spillage can
      convert potentially curable EGC to incurable disease. Patients with preoperative
      findings suspicious for gallbladder cancer should undergo open exploration with
      intent to perform a radical cancer operation as a primary procedure if the
      diagnosis is confirmed intraoperatively.

PMID- 11986019
TI  - American Hepato-Pancreato-Biliary Association: who are we and where are we going?
AB  - The American Hepato-Pancreato-Biliary Association (AHPBA) was initiated in 1994
      following the first World Congress of the International Hepato-Pancreato-Biliary
      Association (IHPBA), which was held in Boston. Presently, the AHPBA has more than
      500 dues-paying members whose median age is in the mid-40s. More than 90% of
      members reside in North America. Approximately 80% of members have completed a
      fellowship in transplantation, hepato-pancreato-biliary surgery and/or research,
      surgical oncology, gastroenterology, or laparoscopy. Approximately 90% have a
      faculty appointment with 80% of these being full-time faculty. More than half of
      the average AHPBA member's time is spent in patient care, but approximately 45%
      of time is divided equally among research, teaching, and administration.
      Approximately 85% of members perform biliary, 75% hepatic, and 45% pancreatic
      surgery, whereas 25% perform liver and pancreatic transplantation. Nearly 90% are
      members of the American College of Surgeons, two thirds The Society for Surgery
      of the Alimentary Tract, 60% the Association for Academic Surgery, and 40% the
      IHPBA. The AHPBA's vision is to be the leading American association devoted to
      hepato-pancreato-biliary education, research, surgical training, and patient care
      and to serve as the American chapter of the IHPBA. The AHPBA mission is as
      follows: (1) to disseminate knowledge of hepato-pancreato-biliary disease,
      techniques, and research; ( 2) to facilitate clinical trials in hepato-pancreato
      biliary disease; (3) to coordinate advanced training in hepato-pancreato-biliary
      surgery; and (4) to foster excellence in the care of patients with hepato
      pancreato-biliary disease. The AHPBA has strategic initiatives to increase
      membership, bring value to a journal affiliation, and enhance its education,
      research, and training missions through multiple collaborations and better
      communication.

PMID- 11986020
TI  - Cystic pancreatic neuroendocrine tumors: is preoperative diagnosis possible?
AB  - Pancreatic neuroendocrine tumors rarely undergo cystic degeneration leading to a
      radiologic appearance, which is often interpreted as a pancreatic mucinous
      cystadenoma or pseudocyst. We reviewed our experience with 38 neuroendocrine
      tumors, four of which were cystic, and 24 other cystic pancreatic tumors
      (mucinous cystadenoma [n = 5], cystadenocarcinoma [n = 6], serous cystadenoma [n
      = 3], solid/cystic papillary neoplasm [n = 3], intraductal papillary mucinous
      tumor [n = 6], and mucinous adenocarcinoma [n = 1]) managed operatively between
      1990 and 2000. This review was undertaken to identify clinical and pathologic
      features useful for preoperative diagnosis of cystic neuroendocrine tumors. Two
      of the four patients with cystic neuroendocrine tumors presented with abdominal
      pain, one patient was asymptomatic, and one patient had hypoglycemia. Three of
      the four cystic neuroendocrine tumors were identified by CT scan, and none were
      biopsied preoperatively. Preoperative diagnoses included mucinous cystadenoma in
      two patients (n = 2), pancreatic cystic neoplasm in one patient, (n = 1) and
      insulinoma in one patient (n = 1). All four cystic neuroendocrine tumors were
      benign and were completely resected (distal pancreatectomy [n = 2], enucleation
      [n = 2]). Cystic neuroendocrine tumors are difficult to diagnose preoperatively
      because the majority of these tumors are nonfunctional, and CT does not
      differentiate these tumors from other cystic neoplasms. Cystic neuroendocrine
      tumors represent a subgroup of pancreatic cystic and neuroendocrine tumors with
      malignant potential. Their high resectability rate further supports the role of
      surgical exploration and resection in the treatment of pancreatic cystic
      neoplasms.

PMID- 11986021
TI  - Diagnostic laparoscopy for periampullary and pancreatic cancer: what is the true
      benefit?
AB  - The role of diagnostic laparoscopy in patients with periampullary and pancreatic
      malignancies is controversial. A retrospective review was performed including all
      patients (n = 188) with a periampullary or pancreatic malignancy who underwent
      both CT and laparotomy at our institution between January 1997 and December 1999.
      The overall resectability rate for all periampullary cancers was 67.3% (115 of
      171 patients). This compared favorably with the resectability rate for cancers of
      the pancreatic body and tail (3 of 17 patients, 17.6%; P < 0.01 vs. periampullary
      cancers). Fifty percent of patients with periampullary cancers were unresectable
      because of metastatic disease, whereas metastatic disease precluded resection in
      64.3% of patients with cancers of the pancreatic body and tail. After patients
      undergoing operative palliation were eliminated, a nontherapeutic laparotomy
      would have been precluded by the use of diagnostic laparoscopy in only 2.3% of
      patients with periampullary cancers (4 of 171 patients). In contrast, 6 (35.3%)
      of 17 patients with cancers of the pancreatic body and tail underwent a
      nontherapeutic laparotomy (P < 0.01 vs. periampullary cancers). One hundred fifty
      eight (84%) of the 188 CT reports reviewed could be definitively categorized as
      either "likely to be resectable" or "likely to be unresectable." The remaining
      16% were equivocal. Of the 107 patients categorized as likely to be resectable,
      89 were actually resected (83.2%). In contrast, only 10 of the 51 patients
      categorized as likely to be unresectable could be resected (19.6%).

PMID- 11986022
TI  - Pancreas-preserving duodenectomy in the management of duodenal familial
      adenomatous polyposis.
AB  - Most patients with familial adenomatous polyposis (FAP) develop disease in the
      duodenum. The duodenal lesions mostly occur in the periampullary region, but some
      patients develop diffuse polyposis involving all parts of the duodenum. These
      neoplastic polyps have malignant potential, and thus warrant surveillance and
      timely intervention. We reviewed our experience with management of FAP over a 10
      year period, focusing on patients who had diffuse polyposis of the duodenum and
      their subsequent management. Three patients with FAP had diffuse duodenal
      involvement, documented by upper gastrointestinal endoscopy. Neoplasia was
      confirmed by endoscopic biopsy, but no patients had histologic evidence of
      carcinoma. The patients underwent resection of the entire duodenum from the
      pylorus to the ligament of Treitz with preservation of the pancreas. Our surgical
      technique is described. One patient had a postoperative wound infection and one
      patient had a biliary leak that resolved with closed suction drainage for 5 days.
      Long-term follow-up in these patients revealed excellent functional status. One
      patient had polyp recurrence in the jejunum at 5-year follow-up, but no patients
      have developed adenocarcinoma. We conclude that patients with duodenal polyps
      associated with FAP may be safely and effectively treated by pancreas-preserving
      duodenectomy.

PMID- 11986023
TI  - Diabetes is associated with increased perioperative mortality but equivalent long
      term outcome after hepatic resection for colorectal cancer.
AB  - Diabetes is associated with alterations in liver metabolism and immune response
      that may influence postoperative recovery and long-term survival after
      hepatectomy for cancer. Patients with type I or type II diabetes mellitus
      submitted to a potentially curative hepatic resection for metastatic colorectal
      cancer were identified from the prospective database, and compared with patients
      with hepatic colorectal metastases submitted to resection during the same time
      interval, but without diabetes mellitus. Data on operative morbidity and
      mortality and long-term survival were analyzed. Between December 1990 and July
      1999, a total of 727 patients underwent hepatic resection, 61 of whom (8.1%) had
      type I and type II diabetes mellitus. Operative mortality in the diabetic
      patients was significantly greater than in nondiabetic patients (8% vs. 2%, P <
      0.02). Among patients with diabetes mellitus, four of the five perioperative
      deaths were due to liver failure after major hepatic resection (lobectomy or
      greater). All four of these patients had significant parenchymal abnormality
      (three with steatosis). Long-term survival was identical to that in nondiabetic
      control subjects. We conclude that the presence of diabetes is associated with a
      higher incidence of perioperative mortality. In patients with diabetes mellitus
      and parenchymal steatosis, major hepatic resection should be undertaken with
      caution.

PMID- 11986024
TI  - Cryosurgery after chemoembolization for hepatocellular carcinoma in patients with
      cirrhosis.
AB  - Most cirrhotic patients with hepatocellular carcinoma (HCC) are not candidates
      for resection. Transarterial chemoembolization (TACE) may ablate a significant
      portion of the tumor but has a high rate of recurrence. Cryosurgery may permit
      successful ablation of hepatic tumors but can be complicated by postoperative
      hemorrhage and is also associated with a significant risk of recurrence. The
      combination of the two techniques might be beneficial. We evaluated in a
      prospective study the safety and efficacy of this combination in cirrhotic
      patients with unresectable HCC. Fifteen patients were included in this study. All
      but one patient underwent one or several sessions of TACE before cryosurgery.
      Cryoablation was successfully performed in each patient. The patient who did not
      undergo preoperative TACE required reoperation for hemorrhage. Another patient
      with Child-Pugh class B cirrhosis died postoperatively of hepatic and multiorgan
      failure. At a mean follow-up of 2.5 years, three patients had recurrence of
      disease, and 13 of 15 patients were alive with the longest survival time being 5
      years. The actuarial survival rate at 5 years was 79%. Cryosurgery after TACE is
      feasible in cirrhotic livers with HCC and can increase the cure rate in large
      tumors. TACE may reduce the risk of hemorrhage after cryosurgery but can increase
      the risk of hepatic failure in patients with poor hepatic function.

PMID- 11986025
TI  - Hepatocellular carcinoma: a prime indication for living donor liver
      transplantation.
AB  - Cadaveric liver transplantation for hepatocellular carcinoma (HCC) is limited by
      donor organ availability. This report reviews our initial experience with living
      donor liver transplantation (LDLT) for HCC. Since August 1998, a total of 71
      adults have undergone LDLT; 27 (38%) for HCC. Underlying diagnoses included
      hepatitis C in 17, hepatitis B in eight, cryptogenic cirrhosis in one, and
      primary biliary cirrhosis in one. Four patients had recurrent HCC after
      resection. Patients with tumors measuring 5 cm or larger received a single dose
      of intravenous doxorubicin intraoperatively and six cycles of doxorubicin at 3
      week intervals beginning 6 weeks postoperatively. All HCC patients are followed
      with CT scans and alpha-fetoprotein measurements every 3 months during the first
      2 years after transplant. Mean waiting time to transplant for patients with HCC
      was 83 days, compared to 414 (P = 0.001) days for 50 patients with HCC who were
      transplanted with cadaveric organs during this period. At median follow-up of 236
      days, there have been four deaths due to non-tumor-related causes and one death
      from recurrence; recurrence has been observed in one other patient. LDLT permits
      expeditious transplantation in patients with early HCC, and provides access to
      transplantation for patients with HCC exceeding the United Network of Organ
      Sharing criteria for prioritization who are, in effect, barred from receiving
      cadaveric organs.

PMID- 11986026
TI  - Effects of hepatitis C virus infection and its recurrence after liver
      transplantation on functional performance and health-related quality of life.
AB  - Our aim was to examine the effects of hepatitis C virus (HCV) infection, a
      leading cause of end-stage liver disease, and its recurrence after liver
      transplantation on functional performance and health-related quality of life.
      Functional performance, liver function, and HCV recurrence were assessed
      longitudinally in 75 adult transplant recipients (28 with HCV). Quality of life
      was reported once after transplantation. Functional performance improved through
      year 2 (P < 0.001) and then declined in those with HCV, whereas the others
      remained stable (P = 0.05). Time had a positive effect (beta = 0.22, P = 0.05)
      and HCV infection had a negative effect (beta = -0.28, P = 0.01) on post
      transplant functional performance. Educational level (beta = 0.24, P < 0.05) and
      recent functional performance (beta = 0.31, P = 0.01) had positive effects on
      quality of life. HCV recurrence was associated with relatively poorer
      pretransplant functional performance, a greater rate of improvement through month
      3 (P < 0.05), and abnormal transaminase values between years 1 and 2 (P < 0.001).
      Rehospitalization for recurrent HCV was associated with reduced functional
      performance (P < 0.05). Functional performance improves with time following liver
      transplantation, but HCV infection exerts an opposing and comparably strong
      effect. Post-transplant functional performance, in turn, directly affects post
      transplant quality of life. Severe, recurrent HCV illness is associated with
      reduced functional performance.

PMID- 11986027
TI  - Repair of bile duct injuries with Gore-Tex vascular grafts: experimental study in
      dogs.
AB  - Bile duct injury is the most feared complication related to biliary tract
      operations. The goal of this investigation was to offer an alternative treatment
      that might prevent this complication. Twelve mongrel dogs, thin-walled FEP-ringed
      Gore-Tex vascular grafts, and Gore-Tex sutures were used in this study. The dogs
      were randomized into three groups of four according to the length of time of
      graft implantation: group 1 = 1 month; group 2 = 2 months; and group 3 = 3
      months. During the first part of the study, a biliary injury was induced by
      ligating the middle choledocus after performing a conventional cholecystectomy.
      During the second part of the study, biliodigestive and biliobiliary anastomosis
      were performed using Gore-Tex vascular grafts prior to resection of the stenotic
      area. Initially, an increase in serum bilirubin and alkaline phosphatase levels
      was noted. Two weeks later, after implantation of the grafts, these values
      returned to normal. Thin-walled FEP-ringed Gore-Tex vascular grafts were found to
      be useful in the repair of bile duct injuries, especially in complete
      transections of the common bile duct. The ductility and flexibility of the
      material allows any type of anastomosis to be performed, especially when bile
      duct-gut anastomosis is technically difficult.

PMID- 11986029
TI  - Concerning results of laparoscopic Nissan fundoplication.

PMID- 11986031
TI  - Effect of the human genome project on the practice of adolescent medicine.
AB  - As the Human Genome Project nears completion, anticipation and speculation about
      its effects on the practice of medicine have increased. This chapter explores the
      various ramifications of the Human Genome Project on the practice of adolescent
      medicine in particular. The potential uses of genetic discoveries for diagnosis,
      prediction, and perhaps treatment are discussed. In addition to potential
      benefits from the completion of the Human Genome Project, however, drawbacks and
      pitfalls also are anticipated, particularly in the areas of confidentiality and
      insurability.

PMID- 11986032
TI  - Advise or consent? Issues in genetic testing of adolescents.
AB  - Medical genetics is a rapidly advancing field, and genetic testing is becoming
      readily accessible as well as more sophisticated. Genetic testing has the
      potential to be both harmful and beneficial in terms of physical, psychosocial,
      and reproductive health. Ethical and legal implications of genetic testing are
      profound and particularly confounding in children and adolescents. This chapter
      discusses points to consider in evaluating the potential benefit and harm of the
      decision to undergo testing in adolescence.

PMID- 11986033
TI  - Adolescent sexuality and disability.
AB  - All human beings are sexual from birth to death and all adolescents, with or
      without chronic illness or disability, must incorporate appropriate concepts of
      sexuality into their process of development from child to adult. This chapter
      reviews normal adolescent development with specific reference to sexuality.
      Potential effects of chronic illness and disability on this process are reviewed,
      including coital behavior, sexual abuse, sexual dysfunction, and sexual
      offending. Management of sexual issues in chronically ill or disabled adolescents
      is considered, including comments about gynecologic needs of disabled girls.

PMID- 11986034
TI  - Genes and athletes.
AB  - Genetics plays an important role in determining characteristics desired for
      success in a given sport. Advances in biotechnology pose interesting and
      perplexing dilemmas for athletes, parents, health care providers, and society at
      large. Gene therapy holds great prospects for disease prevention and treatment.
      The same techniques also can be misused for genetic manipulation to enhance
      athletic prowess. This chapter reviews selective aspects of genotype influence on
      sport performance, uses and misuses of genetic technology, and ethical as well as
      legal dilemmas.

PMID- 11986035
TI  - Pitfalls of genetic diagnosis in the adolescent: the changing face.
AB  - Considerable change occurs in the face, both normal and syndromic, with age.
      Despite knowledge of that change, which we view in ourselves, our family and our
      friends every day, only recently has recognition of phenotypic change been
      incorporated into diagnosis of a genetic syndrome or pattern. This lack of
      awareness can be a substantial pitfall. Over the past 20 years, the author has
      studied facial change in several different conditions, using subjective and
      objective statistical approaches. These studies have revealed age-related changes
      that render the phenotype more subtle, challenging diagnostic acumen. The
      opposite scenario also may occur: the phenotype unfolds with age, and diagnosis
      in infancy and early childhood is more challenging. Syndrome-specific patterns of
      features can be documented objectively, along with the superimposed differential
      rates in facial growth that are the normal process of aging. Measurement of
      facial dimensions can add to or validate a subjective "gestalt" impression. A
      brief review of techniques available for objective assessment of the face is
      provided. Review of serial photographs from birth can enhance diagnostic
      potential by taking into account the phenotype at all ages. This approach is
      particularly helpful in the evaluation of adolescents and adults. Lastly,
      experience should never be underestimated; the opinion of a geneticist may be
      invaluable.

PMID- 11986036
TI  - Adverse environmental exposures in pregnancy: teratology in adolescent medicine
      practice.
AB  - A teratogen is any drug, chemical, infectious or physical agent, or maternal
      disease or altered metabolic state that causes a structural or functional
      disability by acting on the embryo or fetus. Teratogens are responsible for
      approximately 10% of all human birth defects. Education of physicians caring for
      children and adolescents in the basic principles of teratology, the spectrum of
      human teratogens, and the recognition of associated anomalies is essential,
      because many maternal exposures and resultant fetal defects are completely
      preventable.

PMID- 11986037
TI  - Prenatal diagnosis in the adolescent patient.
AB  - Despite a 21% reduction in the birth rate for adolescents aged 15-19 years
      between 1991 and 2000, there are still over 470,000 births to adolescents
      nationwide. The primary purpose of prenatal screening is to determine the risk of
      a disease or condition affecting either the patient or her fetus. A determination
      of risk is possible only after an accurate assessment of all information unique
      to each pregnancy. This assessment includes a medical, obstetrical, social, and
      family history. Ethnicity-based screening tests should be offered to patients at
      risk for specific disorders unique to their ancestry, whereas population-based
      screening tests, such as maternal serum screening and ultrasound screening,
      should be offered to all pregnant women. Invasive diagnostic testing should be
      reserved for patients whose pregnancy has been determined to be at risk for a
      particular disease or condition.

PMID- 11986038
TI  - FISHing for answers: the use of molecular cytogenetic techniques in adolescent
      medicine practice.
AB  - Chromosomal abnormalities are common causes of a variety of diseases, cancers,
      and malformation syndromes. Identification of chromosomal aberrations is
      important for counseling families about prognosis and reproductive risks with
      future pregnancies. However, limited resolution leads to the inability to detect
      small deletions, small insertions or duplications, and complex chromosomal
      rearrangements. Fluorescence-based assays, which have become possible because of
      sophisticated cloning technologies and improved sensitivity of antibody
      conjugates, enable the detection of subtle chromosomal changes beyond the
      resolution of classic cytogenetics. Such techniques have greatly expanded the
      diagnostic armamentarium available in the investigation of adolescents with
      mental retardation, malformations and many other disorders.

PMID- 11986039
TI  - The adolescent with an inborn error of metabolism: medical issues and transition
      to adulthood.
AB  - As patients with inborn errors of metabolism survive longer, understanding of
      potential medical and psychiatric complications adolescence and adulthood has
      increased. In general, detailed therapeutic guidelines for specific metabolic
      disorders are not available, and medical management must be tailored to the
      individual patient. Close interaction between the biochemical genetics clinic
      staff, primary care physician, mental health professional, and other specialists
      is necessary to formulate an integrated care plan. The education of the patient
      and family is a critical function of the biochemical genetics clinic, and
      transition from dependence on parents or other care providers to full
      independence is gradual. The ultimate goal is for the patient to have the
      essential knowledge and motivation required to cope responsibly with dietary and
      medical therapeutic regimens by adolescence or early adulthood. Specific
      illustrative inborn errors of metabolism are discussed (aminoacidemias, urea
      cycle defects, organic acidemias, fatty acid oxidation defects, disorders of
      carbohydrate metabolism, lysosomal storage disorders) in light of potential
      problems encountered in adolescence and adulthood, including issues involving
      pregnancy and long-term medical, psychosocial, and psychiatric complications.

PMID- 11986040
TI  - Rational evaluation of the adolescent with mental retardation.
AB  - Mental retardation in adolescents presents multiple challenges. Among these is
      the frequent lack of an accurate etiologic diagnosis. Retarded youngsters may
      enter adolescence without an established diagnosis; in many, no attempt at
      diagnosis has been made. The diagnostic approach is often more difficult in
      adolescents than in younger children because of the effects of age on physical
      features and changes in the family structure. Despite these challenges, advances
      in cytogenetic technology, cranial imaging, and molecular diagnostics offer
      patients and families real hope that a diagnosis can be achieved, even when
      previous attempts have failed. This chapter discusses the benefits and yield of
      such evaluations. The appropriate clinical and laboratory diagnostic evaluations
      are discussed with attention to the indications for chromosomal analyses,
      molecular testing, cranial imaging, and targeted metabolic testing.

PMID- 11986041
TI  - Medical care and monitoring for the adolescent with Down syndrome.
AB  - As the child with Down syndrome enters the second decade of life, some of the
      original medical issues, such as cardiac, vision, and hearing problems, continue
      to concern parents. Dermatologic and podiatric problems may become particularly
      bothersome. Although the child may be doing well, monitoring for thyroid and
      celiac disease continues to be needed. Continued vigilance is needed for
      arthritis, diabetes, leukemia, neck subluxation, and seizures. Prevention and
      treatment of dental and obesity problems are important. Psychiatric and
      behavioral problems may compromise the adolescent's opportunities. Sexuality and
      the associated issues of abuse, pregnancy, and menstrual hygiene must be
      addressed.

PMID- 11986042
TI  - Turner syndrome.
AB  - The adolescent with Turner syndrome usually enjoys good health, satisfactory
      school performance, and normal peer relationships. Some girls, however, have
      medical, developmental, or social problems that need to be addressed in a timely
      fashion. Newly diagnosed patients require baseline evaluations for
      cardiovascular, endocrine, gastrointestinal, and audiologic abnormalities. In
      those with an established diagnosis, routine health supervision requires an
      expanded and individualized approach that considers the natural history and known
      risk factors. Multiple medical specialists may need to provide additional
      diagnostic and treatment services. Primary care physicians also need to be aware
      of the neurobehavioral and psychosocial complications that may be encountered so
      that they may be an effective advocate for appropriate academic and psychological
      interventions. This chapter focuses on the basic science and clinical aspects of
      Turner syndrome that can serve as a foundation for development of appropriate
      health supervision strategies.

PMID- 11986043
TI  - Diagnosis and management of the adolescent boy with Klinefelter syndrome.
AB  - Klinefelter syndrome is the most common sex chromosome disorder, affecting
      approximately 1/500 to 1/1000 males. The condition results when one or more extra
      X chromosomes are present in the cells of XY fetuses. Although the clinical
      presentation is variable, all males with Klinefelter syndrome demonstrate
      hypogonadism, impaired spermatogenesis, and androgen deficiency. Treatment
      options include testosterone replacement for correction of the androgen
      deficiency and tailoring of school curricula to address specific areas of
      learning difficulties. Adolescence can be a challenging time for any child, but
      for boys with Klinefelter syndrome who receive proper guidance the transition
      through puberty should not be a time for undue anxiety, Most boys with
      Klinefelter syndrome do not differ vastly from their peers. Several
      manifestations of the syndrome, however, should be monitored during adolescence
      and require the primary care physician's attention.

PMID- 11986044
TI  - Genetic and nongenetic factors influencing substance use by adolescents.
AB  - Substance use by adolescents can lead to mortality, physical and social
      morbidity, and a brain disorder called substance dependence if allowed to
      progress to chronic, repetitive self-administration. Substance abuse and
      dependence can begin in adolescence or adulthood, but many of the attitudes and
      behaviors that affect risk become established during adolescence. Genetic risk
      factors have been identified for at least two distinct disorders and more are
      under active study to determine the cause and pathophysiology of addictive
      disorders. Although much remains to be done, a complex interplay of numerous
      genetic and environmental risk factors clearly is involved. An understanding of
      the most important environmental risk factors has led to effective primary
      prevention approaches; knowledge of the genetic risk factors and
      neuropharmacology of drugs of abuse in the brain is beginning to influence
      secondary prevention efforts and treatment, including better medications for
      addictive disorders. A large proportion of adolescents carry a genetic
      vulnerability that can be expressed when they accept peer and societal influences
      that promote experimentation with substances of abuse. At that point, the genetic
      factors take over, maintaining the drug self-administration pattern. Decay of
      social status results from association with drug-using peers and shifts in
      priorities supportive of drug use rather than education and productivity. More
      research into the genetic risk factors and applications of current knowledge to
      treatment is needed.

PMID- 11986047
TI  - Responses of deciduous broadleaf trees to defoliation in a CO2 enriched
      atmosphere.
AB  - Relatively little is known about the implications of atmospheric CO2 enrichment
      for tree responses to biotic disturbances such as folivory. We examined the
      combined effects of elevated CO2 concentration ([CO2]) and defoliation on growth
      and physiology of sugar maple (Acer saccharum Marsh.) and trembling aspen
      (Populus tremuloides Michx.). Seedlings were planted in the ground in eight open
      top chambers. Four chambers were ventilated with CO2-enriched air (ambient + 283
      micromol mol-1) and four chambers were supplied with ambient air. After 6 weeks
      of growth, half of the leaf area was removed on a subset of seedlings of each
      species in each CO2 treatment. We monitored subsequent biomass gain and
      allocation, along with leaf gas exchange and chemistry. Defoliation did not
      significantly affect final seedling biomass in either species or CO2 treatment.
      Growth recovery following defoliation was associated with increased allocation to
      leaf mass in maple and a slight enhancement of mean photosynthesis in aspen.
      Elevated [CO2] did not significantly affect aspen growth, and the observed
      stimulation of maple growth was significant only in mid-season. Correspondingly,
      simulated responses of whole-tree photosynthesis to elevated [CO2] were
      constrained by a decrease in photosynthetic capacity in maple, and were partially
      offset by reductions in specific leaf area and biomass allocation to foliage in
      aspen. There was a significant interaction between [CO2] and defoliation on only
      a few of the measured traits. Thus, the data do not support the hypothesis that
      atmospheric CO2 enrichment will substantially alter tree responses to folivory.
      However, our findings do provide further indication that regeneration-stage
      growth rates of certain temperate tree species may respond only moderately to a
      near doubling of atmospheric [CO2].

PMID- 11986048
TI  - Temporal variation of microfibril angle in Eucalyptus nitens grown in different
      irrigation regimes.
AB  - In 1990, a 2-ha plantation of Eucalyptus nitens (Deane and Maiden) Maiden was
      established in southeastern Tasmania and subjected to different irrigation
      regimes. Point dendrometers were installed in March 1995 to monitor radial stem
      movement every 15 min over several growing seasons. In this study, data from two
      growing seasons (1996-1998) were considered. From these measurements, daily
      increments of stem radius were determined. At the end of the second growing
      season, we extracted 12-mm cores and measured microfibril angles (MFA) of the
      wood at high resolution. Microfibril angles were rescaled on a time axis and
      mapped to daily and distance-based elements. Among treatments, irrigated trees in
      particular formed higher MFA early in the growing season (September-November) and
      lower MFA later in the growing season. Trees subjected to cyclic droughts showed
      clear relationships between MFA and soil water deficits, with MFA increasing in
      response to water stress release. Increases in MFA were preceded by accelerations
      in daily increment of stem radius. Among treatments, trees subjected to severe
      drought had the smallest MFA and generally low fluctuations in MFA. Irrigated
      trees were susceptible to changes in climate, whereas growth of the trees in the
      other treatments was limited by water availability. Use of path-analysis showed
      that temperature had an effect on stem radius increment but not on MFA; wind
      speed was the only factor that influenced MFA directly. Microfibril angle was
      correlated with stem shrinking and expansion phases; growth period length and
      growth rates were positively related to MFA.

PMID- 11986049
TI  - Soil compaction effects on water status of ponderosa pine assessed through
      13C/12C composition.
AB  - Soil compaction is a side effect of forest reestablishment practices resulting
      from use of heavy equipment and site preparation. Soil compaction often alters
      soil properties resulting in changes in plant-available water. The use of
      pressure chamber methods to assess plant water stress has two drawbacks: (1) the
      measurements are not integrative; and (2) the method is difficult to apply
      extensively to establish seasonal soil water status. We evaluated leaf carbon
      isotopic composition (delta13C) as a means of assessing effects of soil
      compaction on water status and growth of young ponderosa pine (Pinus ponderosa
      var. ponderosa Dougl. ex Laws) stands across a range of soil textures. Leaf
      delta13C in cellulose and whole foliar tissue were highly correlated. Leaf
      delta13C in both whole tissue and cellulose (holocellulose) was up to 1.0 per
      thousand lower in trees growing in non-compacted (NC) loam or clay soils than in
      compacted (SC) loam or clay soils. Soil compaction had the opposite effect on
      leaf delta13C in trees growing on sandy loam soil, indicating that compaction
      increased water availability in this soil type. Tree growth response to
      compaction also varied with soil texture, with no effect, a negative effect and a
      positive effect as a result of compaction of loam, clay and sandy loam soils,
      respectively. There was a significant correlation between 13C signature and tree
      growth along the range of soil textures. Leaf delta13C trends were correlated
      with midday stem water potentials. We conclude that leaf delta13C can be used to
      measure retrospective water status and to assess the impact of site preparation
      on tree growth. The advantage of the leaf delta13C approach is that it provides
      an integrative assessment of past water status in different aged leaves.

PMID- 11986050
TI  - Lignification in beech (Fagus sylvatica) grown at elevated CO2 concentrations:
      interaction with nutrient availability and leaf maturation.
AB  - Beech (Fagus sylvatica L.) seedlings were grown in an ambient or elevated CO2
      concentration ([CO2]) either in small stands in microcosms for three to four
      seasons or individually in pots fertilized at different nutrient supply rates.
      Leaves at different stages of development, as well as stems and roots at the end
      of the growing season, were used for analysis of structural biomass and lignin.
      In elevated [CO2], lignification of leaves was slightly retarded compared with
      structural biomass production and showed a strong correlation with the activities
      of ionically, cell-wall-bound peroxidases but not with total soluble peroxidases
      or covalently wall-bound peroxidases. The effect of elevated [CO2] on lignin
      concentration of mature tissues was dependent on nutrient supply rate. In leaves
      and roots, elevated [CO2] increased the lignin concentration in dry mass in N
      limited plants. In seedlings grown with high nutrient supply, the lignin
      concentration in dry mass was unaffected or diminished by elevated [CO2]. Because
      elevated [CO2] enhanced seedling growth in the high nutrient supply treatments,
      the total amount of lignin produced per seedling was higher in these treatments.
      We predict that long-term sequestration of carbon will increase as long as
      biomass production is stimulated by elevated [CO2] and that tissue quality will
      change depending on developmental stage and nutrient availability.

PMID- 11986051
TI  - Minimum cuticular conductance and cuticle features of Picea abies and Pinus
      cembra needles along an altitudinal gradient in the Dolomites (NE Italian Alps).
AB  - Winter desiccation is believed to contribute to stress in coniferous trees
      growing at the treeline because cuticular conductance increases with altitude. To
      test whether winter desiccation occurs in high-altitude conifers of the Dolomites
      (NE Italian Alps), we measured minimum cuticular conductance (g(min)), needle
      wettability (contact angle) and cuticle thickness in Picea abies (L.) Karst. and
      Pinus cembra L. needles from December to August. Samples were collected from
      adult trees along an altitudinal gradient from valley bottom (1050 m a.s.l.) to
      the treeline (2170 m a.s.l.). The treeline site is one of the highest in the area
      and is characterized by a generally low wind exposure. Altitude had no effect on
      g(min) in either species. In P. abies, large seasonal variations in g(min) were
      recorded but no changes were related to needle age class. Pinus cembra had a low
      g(min) and appeared to be efficient in reducing needle water losses. There was a
      significant increase in g(min) with needle aging in P. cembra growing at low
      altitude that could be related to a shorter needle longevity compared with P.
      abies. High contact angles (> 110-120 ) suggested the presence of tubular
      epicuticular waxes on needles of both species. Contact angles were higher (low
      wettability) in high-altitude needles than in low-altitude needles. By the end of
      winter, there was no difference in contact angles between needles in the windward
      and leeward positions. Wax structures transformed toward planar shapes as
      demonstrated by the decrease in contact angle from winter to summer. In both
      species, the cuticle was thicker in needles of high-altitude trees than in
      needles of low-altitude trees and there was no correlation between g(min) and
      cuticle thickness. Because desiccation resistance did not decrease with altitude
      in either species, we conclude that they are not susceptible to winter
      desiccation at the tree line.

PMID- 11986052
TI  - Diurnal changes in gas exchange and carbon partitioning in needles of fast- and
      slow-growing families of loblolly pine (Pinus taeda).
AB  - We investigated diurnal and seasonal changes in carbon acquisition and
      partitioning of recently assimilated carbon in fast- and slow-growing families of
      loblolly pine (Pinus taeda L.) to determine whether fast-growing families
      exhibited greater carbon gain at the leaf level. Since planting on a xeric
      infertile site in Scotland County, NC, USA in 1993, five Atlantic Coastal Plain
      (ACP) and five "Lost Pines" Texas (TX) families have been grown with either
      optimal nutrition or without fertilization (control). In 1998 and 1999, gas
      exchange parameters were monitored bimonthly in four families and needles were
      analyzed bimonthly for starch and soluble sugar concentrations. Although diurnal
      and seasonal effects on net photosynthesis (A(net)) and maximum rate of light
      saturated photosynthesis (A(max)) were significant, few family or treatment
      differences in gas exchange characteristics were observed. The A(net) peaked at
      different times during the day over the season, and A(max) was generally highest
      in May. Instantaneous water-use efficiency (WUE(i)), derived from gas exchange
      parameters, did not differ among families, whereas foliage stable isotope
      composition (delta(13)C) values suggested that TX families exhibited lower WUE
      than more mesic ACP families. Although there were no diurnal effects on foliar
      starch concentrations, needles exhibited pronounced seasonal changes in absolute
      concentrations of total nonstructural carbohydrates (TNC), starch and soluble
      sugars, and in partitioning of TNC to starch and sugars, mirroring seasonal
      changes in photosynthesis and shoot and root growth. In all families, foliar
      starch concentrations peaked in May and decreased to a minimum in winter, whereas
      reducing sugar concentrations were highest in winter. Some family and treatment
      differences in partitioning of recently assimilated carbon in needles were
      observed, with the two TX families exhibiting higher concentrations of TNC and
      starch and enhanced starch partitioning compared with the ACP families. We
      conclude that growth differences among the four families are not a function of
      differences in carbon acquisition or partitioning at the leaf level.

PMID- 11986053
TI  - Changes in foliar spectral reflectance and chlorophyll fluorescence of four
      temperate species following branch cutting.
AB  - Spectral reflectance and chlorophyll fluorescence are rapid non-invasive methods
      that can be used to quantify plant stress. Because variation in ambient light
      (e.g., diurnal patterns of solar radiation) may have a confounding effect on
      these measurements, branches are often excised in the field and then measured
      under controlled conditions in the laboratory. We studied four temperate tree
      species (Abies balsamea (L.) Mill. (balsam fir), Betula papyrifera var.
      cordifolia (Regel) Fern. (paper birch), Picea rubens Sarg. (red spruce) and
      Sorbus americana Marsh. (mountain-ash)) to determine how quickly reflectance and
      fluorescence change following branch cutting. We hypothesized that conifer
      species, which have tough xeromorphic foliage, would exhibit changes more slowly
      than broadleaf species. Furthermore, we hypothesized that keeping broadleaf
      samples cool and moist would delay the onset of reflectance and fluorescence
      changes. In one set of experiments, we did not use any treatments to maintain the
      freshness of cut branches. During the first 12 h following cutting, changes in
      reflectance and fluorescence were slight for all species. Two or 3 days after
      branch cutting, the two conifers still showed only small changes in the ratio of
      variable to maximum fluorescence (Fv/Fm) and most reflectance indices, whereas
      paper birch and mountain-ash showed larger and more rapid declines in Fv/Fm and
      most reflectance indices. We attribute these declines to loss of water. As a
      consequence of xeromorphic leaf structure, the conifers were better able to
      minimize water loss than the two broadleaf species. In another experiment, paper
      birch that had been kept cool and moist after cutting showed only slight changes
      in fluorescence and reflectance, even after 3 days, indicating that with careful
      handling the time interval between collection and measurement of reflectance and
      fluorescence of many broadleaf specimens can be extended to several days. We
      conclude that measurements of reflectance and fluorescence need not be made in
      situ to be accurate and reliable.

PMID- 11986055
TI  - LASIK-induced optic neuropathy.

PMID- 11986056
TI  - LASIK-induced optic neuropathy.

PMID- 11986057
TI  - LASIK-induced optic neuropathy.

PMID- 11986060
TI  - LASIK-induced optic neuropathy.

PMID- 11986061
TI  - Management of pseudophakic malignant glaucoma.

PMID- 11986063
TI  - LASIK-induced optic neuropathy.

PMID- 11986064
TI  - Interferon-induced retinopathy in asymptomatic cancer patients.

PMID- 11986066
TI  - ILM peeling in macular hole surgery.

PMID- 11986069
TI  - Visual halos after sildenafil (Viagra).

PMID- 11986071
TI  - tPA and gas in submacular hemorrhage.

PMID- 11986073
TI  - Intraoperative MMC after excimer laser surgery for myopia.

PMID- 11986075
TI  - Brimonidine 0.2% to prevent post laser IOP elevation.

PMID- 11986079
TI  - TEE in retinal occlusion.

PMID- 11986080
TI  - Adjuvant 5-FU and heparin prevent PVR.

PMID- 11986082
TI  - Take good care of my baby: evolving standards of care for retinopathy of
      prematurity.

PMID- 11986083
TI  - Radiation for optic nerve meningiomas: is this the answer?

PMID- 11986084
TI  - Indecision about corticosteroids for bacterial keratitis: an evidence-based
      update.
AB  - PURPOSE: To quantify the effect of topical corticosteroids on bacterial
      keratitis. CLINICAL RELEVANCE: Bacterial keratitis is an economically important
      infection affecting 1 in 10,000 Americans annually. The predisposing factors,
      prior ocular health, infecting microorganisms, inflammatory severity, and
      therapeutic choices can affect the course and outcome. Antibacterial treatment is
      often curative but does not guarantee good vision. Because many treated patients
      develop a sight-limiting corneal problem, antiinflammatory therapy has sometimes
      been recommended. LITERATURE REVIEWED: Publications from 1950 to 2000 that
      evaluated the effect of corticosteroids on bacterial keratitis in animal
      experiments, case reports and series, case-comparison and cohort studies, and
      clinical trials were systematically identified by electronic and manual search
      strategies. RESULTS: The use of a topical corticosteroid before the diagnosis of
      bacterial keratitis significantly predisposed to ulcerative keratitis in eyes
      with preexisting corneal disease (odds ratio [OR], 2.63; 95% confidence limits
      [CL], 1.41, 4.91). Once microbial keratitis occurred, prior corticosteroid use
      significantly increased the odds of antibiotic treatment failure or other
      infectious complications (OR, 3.75; 95% CL, 2.52, 5.58). However, the effect of a
      topical corticosteroid with antibiotics after the onset of bacterial keratitis
      was unclear. Experimental models suggested likely advantages, but clinical
      studies did not show a significant effect of topical corticosteroid therapy on
      the outcome of bacterial keratitis (OR, 0.62; 95% CL, 0.25, 1.54). CONCLUSIONS:
      Topical corticosteroids increase the risk of infectious complications affecting
      the cornea but may or may not have an effect during antibacterial therapy. The
      unproven role of corticosteroids in the adjunctive treatment of bacterial
      keratitis highlights the need to collect prospective information that would guide
      appropriate management for this common eye disease.

PMID- 11986086
TI  - The effects of cidofovir 1% with and without cyclosporin a 1% as a topical
      treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot
      study.
AB  - OBJECTIVE: To evaluate the efficacy of cidofovir 1% eyedrops with and without
      cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis
      (AKC). DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four patients
      with acute adenoviral keratoconjunctivitis of recent onset. METHODS: Patients
      were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir
      10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily,
      and 4) sodium chloride four times daily (control). The diagnosis was confirmed by
      adenoviral polymerase chain reaction from conjunctival swabs. Duration of
      treatment was 21 days. MAIN OUTCOME MEASURES: Severity of conjunctival injection,
      conjunctival chemosis, punctate epithelial keratitis during the course of
      treatment, and presence and severity of corneal subepithelial infiltrates were
      evaluated by a clinical score. Duration until subjective improvement of symptoms
      was recorded. RESULTS: The frequency of severe corneal opacities was lower with
      cidofovir (P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and
      the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were
      clinically similar to the signs of the initial viral inflammation. They first
      appeared 8 to 12 days after beginning of treatment and completely subsided 7 to
      28 days after discontinuation of cidofovir. The outcome measures of local
      inflammation did not differ between the four treatment groups. Cyclosporin A did
      not alter the course of the infection. CONCLUSIONS: Cidofovir lowers the
      frequency of severe corneal opacities, but its clinical use 4 to 10 times daily
      at a 1% concentration is limited by local toxicity. Further clinical studies to
      find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an
      improved pharmaceutical preparation, are required.

PMID- 11986087
TI  - Tuberculin skin testing in uveitis patients and treatment of presumed intraocular
      tuberculosis in Japan.
AB  - PURPOSE: To evaluate the results of tuberculin skin testing in Japanese patients
      with intraocular inflammation and to assess the outcome of treatment for presumed
      intraocular tuberculosis in selected patients. DESIGN: Prospective,
      noncomparative, interventional case series. PARTICIPANTS: One hundred twenty-six
      patients, newly referred to the Ocular Inflammation Service at the Kyorin Eye
      Center from April 1998 to August 2000, underwent systemic evaluation for the
      diagnosis and/or treatment of uveitis. METHODS: Tuberculin skin testing with
      purified protein derivative was performed as part of the systemic evaluation. The
      diagnosis of presumed intraocular tuberculosis was made when findings were
      consistent with possible intraocular tuberculosis, the tuberculin skin test was
      positive (induration more than 10 mm), and no other cause of uveitis was
      suggested by symptoms, signs, or ancillary testing. Using these criteria, 10
      patients were given a diagnosis of presumed intraocular tuberculosis and treated
      with antituberculosis therapy consisting of isoniazid, with or without
      rifampicin. Some of these patients also received a tapered course of oral
      corticosteroids after the initiation of antituberculosis treatment. None of the
      patients had any signs or symptoms of acquired immunodeficiency syndrome. MAIN
      OUTCOME MEASURES: Visual acuity and ophthalmologic examination to assess degree
      of intraocular inflammation. RESULTS: Twenty-six of the 126 patients (20.6%) had
      a positive tuberculin skin test result. Ten of these 26 patients (38.5%) were
      treated for a diagnosis of presumed intraocular tuberculosis. Nine patients had
      no evidence of pulmonary tuberculosis, and one patient had presumed tuberculous
      hilar lymphadenitis. The predominant clinical finding was choroidal or optic disc
      nodule in three patients, retinal vasculitis in three patients, and choroiditis
      in four patients. Nine patients exhibited decreased intraocular inflammation with
      treatment. CONCLUSIONS: Roughly one fifth of the uveitis patients who underwent
      systemic evaluation had a positive tuberculin skin test result, and 9 of 10
      selected skin test-positive patients with clinical findings consistent with
      intraocular tuberculosis had a favorable response to antituberculosis therapy.
      These results suggest that intraocular tuberculosis continues to be a major
      diagnostic consideration for uveitis patients in Japan.

PMID- 11986088
TI  - Induced sputum for identifying sarcoidosis in patients with uveitis.
AB  - OBJECTIVE: To evaluate the value of the induced sputum technique in diagnosing
      sarcoidosis as the cause of uveitis. DESIGN: Comparative case series.
      PARTICIPANTS: Seventeen patients with uveitis. Two control groups were used. The
      first included 10 patients with sarcoid without uveitis; the second included 5
      healthy volunteers. TESTING: Sputum was induced by a 20-minute inhalation of 3.5%
      saline using an ultrasonic nebulizer. Samples were studied by differential counts
      of 200 cells on cytopreps stained by Giemsa. T lymphocyte subset analyses were
      done by fluorescence-activated cell sorter using the monoclonal antibodies CD4 (T
      helper cells) and CD8 (T suppressor-cytotoxic cells). Angiotensin-converting
      enzyme (ACE) serum levels were obtained. MAIN OUTCOME MEASURES: A CD4/CD8 ratio
      >2.5 and an ACE level >145 microl/ml/minute were considered to be abnormal.
      RESULTS: The difference in the CD4/CD8 ratios in the induced sputum examination
      between the group of patients with an elevated ACE level and the group of
      patients with an ACE level within normal limits was statistically significant (P
      = 0.0001). CONCLUSIONS: The induced sputum examination showed increased CD4/CD8
      ratios in patients with uveitis who also had elevated ACE levels, suggesting the
      presence of sarcoidosis.

PMID- 11986089
TI  - Limbal stem cell transplantation in chronic inflammatory eye disease.
AB  - OBJECTIVE: The goal of this study was to describe the outcome of limbal stem cell
      transplantation (LSCT) in patients with severe ocular surface disease caused by
      underlying chronic inflammatory eye disease. DESIGN: Retrospective noncomparative
      case series. PARTICIPANTS: Nine patients with limbal stem cell deficiency caused
      by an underlying ocular inflammatory disease who underwent LSCT. METHODS: The
      authors reviewed the records of 11 eyes of 9 patients with immunologically
      mediated ocular surface disease that underwent LSCT. MAIN OUTCOME MEASURES: The
      main outcome measures were reepithelialization of the corneal surface,
      restoration of corneal surface, and improvement in visual acuity. RESULTS: A
      total of 11 eyes underwent either autologous (n = 1) or HLA-matched living
      related donor (n = 10) LSCT for ocular surface disease secondary to inflammatory
      disease. Reepithelialization of the corneal surface in the immediate
      postoperative period occurred in 10 eyes (91%) within an average of 10 days
      (range, 3-21 days). Long-term restoration of the corneal surface was achieved in
      six (55%) eyes. Visual acuity improved in six eyes (55%). Reasons for poor
      outcomes included microbial infection, limbal stem cell graft rejection, and
      corneal ulceration. No donor eyes had complications. CONCLUSIONS: Patients with
      underlying immunologically mediated diseases, such as Stevens-Johnson syndrome,
      toxic epidermal necrolysis, or ocular cicatricial pemphigoid, who undergo LSCT
      have lower success rates than do those patients with noninflammatory ocular
      surface diseases.

PMID- 11986090
TI  - Ocular toxoplasmosis: clinical features and prognosis of 154 patients.
AB  - PURPOSE: To ascertain the clinical features, visual outcome, and recurrence rates
      of ocular toxoplasmosis (OT) in a large series of patients. To determine the
      efficacy of various treatment strategies and identify the patients at risk of
      visual loss. DESIGN: Retrospective noncomparative observational case series.
      PARTICIPANTS: One hundred fifty-four consecutive patients with active lesions of
      OT (first attack and/or recurrence) were identified in a cohort of 1300
      consecutive patients with uveitis. Mean follow-up was 5.8 years. INTERVENTION: A
      review of the medical records of 154 patients with active OT. MAIN OUTCOME
      MEASURES: Patients were subdivided according to clinical and laboratory criteria.
      Numerous variables were compared per patient and group, including age and gender
      distribution, onset and course of infection, clinical ocular features, laboratory
      data, therapeutic strategies and their outcomes, number of recurrences,
      complications, final visual acuity, and features associated with poor visual
      outcome. RESULTS: Primary retinal lesions were observed in 28% and a combination
      of active lesions and old retinochoroidal scars in 72% of the patients at first
      presentation to the ophthalmologist. Mean age at first presentation with an
      active OT lesion was 29.5 years. Patients with primary OT were older than those
      with a combination of active lesions and old scars (P < 0.001). Serologic
      characteristics of the acute phase of systemic infection were found in 11% of the
      patients. Ocular involvement in these patients was associated with advanced age
      at onset (P < 0.001) and was characterized by severe intraocular inflammation.
      Most (82%) of the patients with serologic characteristics of the acute phase of
      systemic infection had primary lesions (compared with 23% of OT in the chronic
      phase of systemic infection; P < 0.001). Extensive retinal lesions were more
      frequently observed during the acute phase of systemic infection (P = 0.02) and
      in patients with primary OT (P < 0.04). Recurrences, which developed in 79% of
      all patients followed for more than 5 years, were located predominantly in
      previously affected eyes (with old scars) in contrast to the sporadic cases of
      recurrence in the healthy contralateral eye (P < 0.0001). Standard short-term
      therapeutic modalities had no effect on visual outcome or future recurrence
      rates. Legal blindness in one or both eyes was confirmed for 24% of the patients.
      Blindness of both eyes was more frequent in patients with congenital OT (P <
      0.001). Risk factors for visual loss included congenital infection, OT
      manifesting during the acute phase of systemic infection, central location and/or
      extensive retinal lesions, and the administration of corticosteroids without a
      shield of antiparasitic drugs. CONCLUSIONS: Legal blindness in at least one eye
      developed in 24% of the patients with OT. Recurrences, which developed in 79% of
      the patients with long-term follow-up, were located predominantly in eyes with
      toxoplasmic scars. Various short-term therapeutic modalities had no effect on
      visual outcomes or future recurrence rates, with the exception of a poor visual
      outcome for patients who received corticosteroids without a shield of
      antiparasitic drugs.

PMID- 11986091
TI  - Cytomegalovirus as a cause of anterior uveitis with sectoral iris atrophy.
AB  - OBJECTIVE: To report two cases of recurrent anterior uveitis with sectoral iris
      atrophy and ocular hypertension during attacks caused by cytomegalovirus (CMV).
      DESIGN: Two observational case reports. PARTICIPANTS: Two immunocompetent
      patients with a history of recurrent unilateral hypertensive anterior uveitis
      with sectoral iris atrophy were referred to us with the presumptive diagnosis of
      herpetic uveitis. MAIN OUTCOME MEASURES: Comprehensive ophthalmic examination,
      aqueous humor polymerase chain reaction (PCR), and peripheral blood serologic
      studies were performed on both patients. RESULTS: Examination of aqueous humor by
      PCR was positive for CMV and negative for herpesvirus. Serum IgG/IgM titers
      disclosed past CMV infection. Both patients responded well to antiviral therapy
      with ganciclovir. The final visual acuity level was 20/20 in both eyes of both
      patients. CONCLUSIONS: CMV infection can produce recurrent attacks of anterior
      uveitis with clinical characteristics indistinguishable from those previously
      considered highly suggestive or even pathognomonic for herpetic infection. This
      observation has implications for the therapeutic management of such patients.

PMID- 11986092
TI  - The Chirila Keratoprosthesis: phase I human clinical trial.
AB  - OBJECTIVE: To undertake a preliminary safety and performance evaluation of an
      artificial cornea, the Chirila Keratoprosthesis, in human patients. DESIGN: A
      prospective, interventional case series. PARTICIPANTS: Fourteen consecutive
      patients with blindness of corneal origin not treatable by repeated standard
      penetrating keratoplasty. METHODS: Keratoprostheses were manufactured and
      implanted. The patients, all with preoperative visual acuity of light perception
      to count fingers (CF), were followed clinically in adherence to a protocol. MAIN
      OUTCOME MEASURES: Safety (keratoprosthesis retention, incidence of serious
      complications) and performance (visual acuity, comfort, appearance). RESULTS:
      Ninety-three percent of keratoprostheses were retained to the date of reporting,
      up to 2.5 years. One keratoprosthesis (7%) was removed in a manner that restored
      the patient's preoperative condition. All but one patient maintained their
      preoperative level of visual acuity or improved on it, with most achieving their
      estimated full potential visual acuity, (range, count fingers - 20/20).
      CONCLUSIONS: This keratoprosthesis is acceptably safe and has demonstrated an
      ability to restore vision in cases in which alternative management would have had
      a poor prognosis. More extensive trials are warranted.

PMID- 11986093
TI  - A long-term visual outcome comparison in patients with optic nerve sheath
      meningioma managed with observation, surgery, radiotherapy, or surgery and
      radiotherapy.
AB  - PURPOSE: Comparison of treatment outcome in patients with primary optic nerve
      sheath meningioma (ONSM). DESIGN: Retrospective, nonrandomized, comparative
      interventional case series. PARTICIPANTS: Sixty-four patients with at least 50
      months of well-documented follow-up. INTERVENTION: Observation, surgery only,
      radiotherapy only, or surgery and radiotherapy. MAIN OUTCOME MEASURES: Visual
      acuity expressed as ratio, radiographic progression, and treatment complications.
      RESULTS: Sixty-four patients (55 women [85.9%] and nine men [14.1%]) were
      followed for a mean of 150.2 months (range, 51-516 months; standard deviation
      [SD], 74.7). The mean age at diagnosis was 47.1 years (range, 17-81 years; SD,
      15.4). Fifty-eight patients had unilateral disease and six patients had bilateral
      disease. Of 59 patients with vision greater than no light perception at
      diagnosis, 13 patients were observed only, 12 had surgery only (four biopsies or
      partial resections, eight total resections), 18 received radiation alone, and 16
      had surgery and radiation (14 biopsies or partial resections and radiation, two
      total resections and radiation). Irradiated patients received 4000 to 5500 cGy of
      conventional multiport or conformal external beam therapy, typically fractionated
      over 6 weeks. Visual acuity measurements at diagnosis among the four groups were
      not different (ratio, P = 0.186). Visual acuity at diagnosis was > or =0.5 in
      56.3%, 0.4 to 0.050 in 12.5%, and <0.050 in 31.3%. Visual acuity measures at last
      follow-up were different among the four groups (ratio, P = 0.004). At last follow
      up the acuity was > or =0.5 in 28.1%, 0.4 to 0.050 in 15.6%, and <0.050 in 56.3%.
      Visual acuity fell significantly for the observed only (ratio, P = 0.002),
      surgery only (ratio, P = 0.019), and surgery with radiation groups (ratio, P =
      0.030). The radiation only group showed a decrease in visual acuity that was not
      significant (ratio, P = 0.301). Complication rate was 33.3% in radiation only
      cases, 66.7% in surgery only cases, and 62.5% in surgery with radiation cases.
      Twenty-one patients (32.8%) showed radiographic progression. Four patients who
      were observed, seven patients who had surgery alone, and eight patients who had
      surgery and radiation developed radiographic progression. Two patients who had
      radiation alone had radiographic progression before treatment. Only two patients
      treated with radiation only showed radiographic progression after radiotherapy,
      and both had at least one surgical procedure before the radiotherapy.
      CONCLUSIONS: Patients with ONSM receiving radiation alone demonstrated the best
      visual outcome during the follow-up period. We recommend that fractionated
      external beam radiation (5000-5500 cGy) be considered as initial treatment in
      adults in selected cases of ONSM when preservation of visual function is a
      reasonable therapeutic goal.

PMID- 11986095
TI  - Clinicopathologic features and behavior of cutaneous eyelid melanoma.
AB  - OBJECTIVE: To study the clinical and histopathologic features of cutaneous eyelid
      melanomas and identify prognostic factors in the behavior of such tumors. DESIGN:
      Retrospective observational case series. PARTICIPANTS: Twenty-three patients with
      cutaneous eyelid melanomas without conjunctival involvement. METHODS: Patients'
      charts were reviewed for clinical information, treatment procedure, and disease
      course (updated at the time of study). Histopathologic sections from all surgical
      procedures were reviewed. MAIN OUTCOME MEASURES: Histologic type of melanoma,
      tumor growth phase, Clark's level of invasion, tumor thickness, and other
      microscopic features were evaluated in each case. The width of excision margins
      was considered and measured histologically when possible. RESULTS: There was no
      gender predilection. The lower eyelid was more frequently involved than the upper
      eyelid or canthi. Seventeen cases (74%) were invasive, and six (26%) were in situ
      melanomas. Lentigo maligna melanoma was the most common histologic type,
      accounting for 61% (14 cases) of all melanomas and 53% (9 cases) of invasive
      melanomas. Superficial spreading melanoma accounted for 22% (5 cases) and nodular
      melanoma for 17% (4 cases) of all melanomas. Surgical excision, as the treatment
      of choice, was incomplete in nine cases, two thirds of which were lentigo maligna
      melanoma (in situ or invasive). Tumor reappeared in 77.8% of these cases.
      Fourteen patients had initial narrow excisions, and three of them (21.4%) had
      local recurrences. Although recurrence occurred in one each of our "in situ,"
      "thin," and "thick" melanomas, it proceeded to distant metastases and death only
      in the "thin" one. Adjuvant radiotherapy was used in six patients with successful
      disease control in two cases. CONCLUSIONS: Eyelid skin melanomas have a
      relatively good clinical prognosis. The histologic type and thickness of the
      primary melanoma were not clearly related to the clinical behavior once they were
      completely excised. The use of very narrow excisions of 5 mm or less was
      associated with greater frequency of local recurrence. Lentigo maligna melanomas
      were the largest tumors at presentation and, despite being thinner, were a
      greater surgical challenge. This type of melanoma is almost certainly
      underdiagnosed by ophthalmologists.

PMID- 11986096
TI  - Incidence of radiation retinopathy after high-dosage single-fraction gamma knife
      radiosurgery for choroidal melanoma.
AB  - OBJECTIVE: To investigate the incidence and clinical findings of radiation
      retinopathy after single-fraction high-dose gamma knife radiosurgery for
      choroidal melanoma. DESIGN: Retrospective noncomparative interventional case
      series. PARTICIPANTS: Thirty-two patients with choroidal melanoma. METHODS:
      Review of charts, color fundus photographs, and fluorescein angiograms of 32
      choroidal melanoma patients after radiosurgery. All patients were treated with
      the Leksell gamma knife in one fraction with a marginal dose between 40 and 80 Gy
      (median, 50 Gy) and were followed for at least 24 months (or until enucleation
      because of complications secondary to radiation). MAIN OUTCOME MEASURES: Any
      clinical feature of radiation retinopathy and neovascular glaucoma. RESULTS:
      During a mean follow-up of 38 months (range, 6-81 months) we found radiation
      retinopathy in 84% of our patients. The most common findings in these patients
      were intraretinal hemorrhages with an incidence of 70%, macular edema and
      capillary nonperfusion in 63%, and hard exudates in 52% of the patients. Less
      common were microaneurysms in 30% and retinal neovascularization in 22%. The time
      of onset of the various radiation-associated retinal findings ranged between 1
      and 22 months. Forty-seven percent of all patients developed neovascular
      glaucoma. In our study there was no correlation between radiation dosage applied
      and clinical findings. CONCLUSIONS: Single-fraction high-dose Leksell gamma knife
      radiosurgery of choroidal melanomas with a median marginal dose of 50 Gy is
      highly associated with early radiation retinopathy and with neovascular glaucoma.

PMID- 11986097
TI  - Corneally displaced malignant conjunctival melanomas.
AB  - PURPOSE: To characterize and classify malignant conjunctival melanomas with
      exclusively corneal invasive growth. DESIGN: Population-based, nationwide
      retrospective cross-sectional study. PARTICIPANTS: Patients with primary
      malignant conjunctival melanoma diagnosed between 1967 and 2000 in Finland.
      METHODS: On the basis of all available clinical and histopathologic data of
      tumors diagnosed during the study period, malignant conjunctival melanomas that
      first demonstrated invasive growth on the cornea without evidence of conjunctival
      tumors other than primary acquired melanosis were identified, their prevalence
      calculated, and their characteristics reviewed. On the basis of these cases and
      literature data, a classification for "corneal melanoma" was developed. MAIN
      OUTCOME MEASURES: Frequency and type of corneal involvement, recurrence, and
      survival. RESULTS: Patients with exclusively corneal invasive tumor accounted for
      5% (95% confidence interval, 1-12) of 85 consecutive primary conjunctival
      melanomas. Two were separated from the limbus by clear cornea (type I), and two
      paralleled but did not invade the limbal conjunctiva (type II). Two were
      associated with clear evidence of primary acquired melanosis. None of the tumors
      recurred after local excision, and no metastases were observed during a median
      follow-up of 2 years 5 months (range, 1 year 8 months-7 years 10 months).
      CONCLUSIONS: Primary malignant conjunctival melanomas can grow on the cornea
      without conjunctival involvement other than acquired melanosis. They are easily
      removed and do not cause lymphatic metastases. The term "corneally displaced
      malignant conjunctival melanoma" would best describe their supposed conjunctival
      origin and actual corneal location.

PMID- 11986098
TI  - Intravitreal triamcinolone for refractory diabetic macular edema.
AB  - PURPOSE: To determine if intravitreal injection of triamcinolone acetonide is
      safe and effective in treating diabetic macular edema unresponsive to prior laser
      photocoagulation. DESIGN: Prospective, noncomparative, interventional case
      series. PARTICIPANTS: Sixteen eyes with clinically significant diabetic macular
      edema (CSME) that failed to respond to at least two previous sessions of laser
      photocoagulation. METHODS: Eyes were diagnosed with CSME and treated with at
      least two sessions of laser photocoagulation according to Early Treatment
      Diabetic Retinopathy Study guidelines. At least 6 months after initial laser
      therapy, the response was measured by clinical examination and optical coherence
      tomography (OCT). Eyes with a residual central macular thickness of more than 300
      microm (normal, 200 microm) and visual loss from baseline were offered
      intravitreal injection of 4 mg triamcinolone acetonide. The visual and anatomic
      responses were observed as well as complications related to the injection
      procedure and corticosteroid medication. MAIN OUTCOME MEASURES: Visual acuity and
      quantitative change in OCT macular thickening were assessed. Potential
      complications were monitored, including intraocular pressure response, cataract
      progression, retinal detachment, vitreous hemorrhage, and endophthalmitis.
      RESULTS: All patients completed 3 months of follow-up, and 8 of 16 patients (50%)
      completed 6 or more months of follow-up. Mean improvement in visual acuity
      measured 2.4, 2.4, and 1.3 Snellen lines at the 1-, 3-, and 6-month follow-up
      intervals, respectively. The central macular thickness as measured by OCT
      decreased by 55%, 57.5%, and 38%, respectively, over these same intervals from an
      initial pretreatment mean of 540.3 microm (+/-96.3 microm). Intraocular pressure
      exceeded 21 mmHg in 5, 3, and 1 eye(s), respectively, during these intervals. One
      eye exhibited cataract progression at 6 months. No other complications were noted
      over a mean follow-up of 6.2 months. Reinjection was performed in 3 of 8 eyes
      after 6 months because of recurrence of macular edema. CONCLUSIONS: Intravitreal
      triamcinolone is a promising therapeutic method for diabetic macular edema that
      fails to respond to conventional laser photocoagulation. Complications do not
      appear to be prohibitive. Further study is warranted to assess the long-term
      efficacy and safety, and the need for retreatment.

PMID- 11986099
TI  - A comparison of laser photocoagulation with cryotherapy for threshold retinopathy
      of prematurity at 10 years: part 1. Visual function and structural outcome.
AB  - OBJECTIVE: To assess visual and structural outcomes after laser photocoagulation
      and transscleral cryotherapy for threshold retinopathy of prematurity (ROP) after
      10 years. DESIGN: Extended follow-up of a randomized controlled clinical trial.
      PARTICIPANTS: One hundred eighteen eyes from 66 patients were randomly assigned
      to receive either cryotherapy or laser photocoagulation for threshold ROP. Forty
      four eyes from 25 patients were examined for 10-year follow-up evaluations.
      INTERVENTION: Early Treatment of Diabetic Retinopathy Study (ETDRS) visual
      acuity, slit-lamp, and fundus examination; fundus photography; and B-scans (eyes
      with retinal detachments) were performed. Patients' histories were taken to
      elicit past amblyopia therapy. Based on fundus photographs, independent observers
      graded the degree of retinal dragging as none, mild, moderate, or severe. MAIN
      AND SECONDARY OUTCOME MEASURES: Best-corrected ETDRS visual acuity (BCVA). The
      degree of dragging was determined clinically and photographically. In addition,
      the presence of strabismus or amblyopia and/or any history of treatment for
      amblyopia were noted accordingly. RESULTS: Eyes treated with laser had a mean
      BCVA of 20/66 (Snellen equivalent), whereas cryotherapy-treated eyes had a mean
      BCVA of 20/182 (Snellen equivalent) (P = 0.015, n = 42). Compared with eyes
      treated with cryotherapy, eyes treated with laser photocoagulation were 5.2 times
      more likely to have a 20/50 or better BCVA (95% confidence interval, 1.37-19.8, n
      = 42). Eyes treated with cryotherapy were 7.2 times (95% confidence interval,
      1.54-33.6, n = 33) more likely to develop retinal dragging compared with laser
      treatment. By linear regression analysis, ETDRS visual acuity was inversely
      proportionate to the degree of retinal dragging in both laser (r = -0.637, P =
      0.006) and cryotherapy (r = -0.517, P = 0.040) treated eyes. Among the 21
      patients with favorable outcomes in both eyes, 13 had strabismus (62%) and 6 had
      received amblyopia therapy (29%). Ptosis, loss of cilia, and cortical cataract
      were among probable treatment-related complications that were noted in this
      study. CONCLUSIONS: Overall, laser-treated eyes had better structural and
      functional outcome compared with eyes treated with cryotherapy.

PMID- 11986101
TI  - A comparison of laser photocoagulation with cryotherapy for threshold retinopathy
      of prematurity at 10 years: part 2. Refractive outcome.
AB  - OBJECTIVE: To compare the refractive outcome of eyes treated with cryotherapy for
      threshold retinopathy of prematurity (ROP) with eyes treated with laser
      photocoagulation. DESIGN: Extended follow-up of a randomized controlled clinical
      trial. PARTICIPANTS: One hundred eighteen eyes from 66 patients were randomly
      assigned to receive either cryotherapy or laser photocoagulation for threshold
      ROP. Twenty-five patients (44 eyes treated) were available for follow-up
      examination 10 years later. INTERVENTION: Cycloplegic autorefraction or
      retinoscopy was performed. Immersion ultrasound biometry (A-scan) was also
      performed, and an autokeratometer was used for keratometry. If an A-scan could
      not be tolerated or the patient was not cooperative, a B-scan through-the-lid
      biometry was performed. Corneal thickness was measured using optical coherence
      tomography. MAIN AND SECONDARY OUTCOME MEASURES: Refractive error. In addition,
      anterior chamber depth, lens thickness, and axial length were measured. Central
      corneal thickness measurements and keratometric readings were also obtained.
      RESULT: Eyes treated with cryotherapy were significantly more myopic than those
      treated with laser photocoagulation. When comparing patients with bilateral
      treatment, the mean spherical equivalent (SE) of eyes treated with laser was 
      4.48 diopters (D) compared with a mean SE of -7.65 D for eyes treated with
      cryotherapy (n = 15 pairs of eyes, P = 0.019). Cryotherapy-treated eyes had a
      mean axial length of 21.7 mm versus 22.9 mm for laser-treated eyes (P = 0.024, n
      = 12 pairs of eyes). The anterior chamber depth and lens thickness averaged 2.86
      mm and 4.33 mm, respectively, in the cryotherapy-treated eyes compared with 3.42
      mm and 3.95 mm in the laser-treated eyes (P < 0.001, n = 12 pairs for both
      measurements). There were no statistical differences in anterior corneal
      curvature and central corneal thickness between the two treatment modalities.
      Crystalline lens power bore the strongest correlation to refractive outcomes in
      both laser-treated (r = 0.885, P < 0.001) and cryotherapy-treated eyes (r =
      0.591, P = 0.026). Although keratometric readings were higher than normal values
      in these eyes, there was no correlation to the degree of myopia. CONCLUSIONS:
      Laser-treated eyes were significantly less myopic than cyrotherapy-treated eyes.
      Lens power seemed to be the predominant factor contributing to the excess myopia.

PMID- 11986102
TI  - Ophthalmic findings in fetal anticonvulsant syndrome(s).
AB  - PURPOSE: To report the prevalence of ocular abnormalities in a group of children
      diagnosed with fetal anticonvulsant (FAC) syndrome(s). DESIGN: Retrospective,
      observational, noncomparative case series. PARTICIPANTS: Forty-six children, age
      range 8 months to 16 years 5 months (mean, 7 years 1 month), with a confirmed
      diagnosis of an FAC syndrome. Thirty-seven subjects were exposed in utero to
      sodium valproate (29 as monotherapy), and the remainder (n = 9) to other
      anticonvulsants, mainly carbamazepine. METHODS: A total of 46 subjects underwent
      ophthalmic assessment consisting of visual acuity, cover test, ocular movements,
      analysis of spectacle lens power, cycloplegic refraction, and anterior segment
      examination with portable slit lamp, plus direct and indirect ophthalmoscopy.
      MAIN OUTCOME MEASURES: Refraction and ocular motility status. RESULTS: Thirty-one
      of 46 (67%) had ocular abnormalities, most commonly errors of refraction (19 of
      46; 41%). Myopia was common (14 of 28; 50%) in those exposed to valproate
      monotherapy and there were high frequencies of strabismus (20%), astigmatism
      (24%), and anisometropia (11%) in the group as a whole. Thirty-one percent of
      myopes and 27% of astigmates did not wear glasses, of whom three subjects and two
      subjects, respectively, were less than 8 years old and therefore at risk of
      anisometropic or ametropic amblyopia. One subject had epicanthus, one color
      vision deficiency, and one bilateral congenital cataract. CONCLUSIONS: We
      conclude that (1) abnormal ophthalmic findings are common in subjects with
      confirmed FAC syndrome, in particular myopia in those with fetal valproate
      syndrome; (2) children with FAC syndrome should receive preschool vision testing;
      (3) preschool vision testing should be considered in all children exposed to
      anticonvulsants in utero.

PMID- 11986103
TI  - Outcome of phacoemulsification after pars plana vitrectomy.
AB  - PURPOSE: To compare the outcome of phacoemulsification surgery in patients with
      and without prior vitrectomy, adjusted for confounding factors. DESIGN:
      Retrospective cohort study. PARTICIPANTS AND CONTROLS: Thirty-one consecutive
      eyes undergoing phacoemulsification after pars plana vitrectomy (PPV) and 116
      consecutive eyes undergoing phacoemulsification without previous PPV. METHODS:
      Office records of the operating surgeons were reviewed for age, gender, type of
      cataract, vitrectomy status, best-corrected visual acuity (BCVA) before and after
      phacoemulsification, intraoperative difficulties, and postoperative
      complications. Bivariate analyses between these predictors and the main outcome,
      BCVA of 20/40 or better after phacoemulsification, were performed using Pearson's
      chi-square tests. An adjusted analysis of the relationship between outcome and
      vitrectomy status was performed with logistic regression. Pearson's chi-square
      tests were used to compare type of cataract, intraoperative difficulties, and
      postoperative complications in study and control eyes. MAIN OUTCOME MEASURES:
      BCVA of 20/40 or better after phacoemulsification, rates of intraoperative
      difficulties, and postoperative complications. RESULTS: The most common
      indication for PPV was macular hole. The average interval from PPV to
      phacoemulsification was 15.4 months. Study eyes were followed for an average of
      10 months compared with 6.6 months for controls. Study eyes were more likely than
      controls to have predominantly nuclear sclerotic cataracts (P = 0.002). After
      cataract extraction, 24 of 31 study eyes (77.4%) and 110 of 116 control eyes
      (94.8%), had BCVAs of 20/40 or better. After adjusting for confounders, eyes
      without previous vitrectomy were 3.44 times more likely to obtain a BCVA of 20/40
      or better than eyes with prior PPV, but this difference was not statistically
      significant (95% CI, 0.72-16.67). Only 3 of 31 (9.7%) study and 11 of 116 (9.4%)
      control eyes had intraoperative difficulties (P = 0.47). Posterior capsule plaque
      was the most common intraoperative difficulty in study eyes; small pupil
      requiring stretching or iris hooks was most common in controls. Only 1 of 31
      (3.2%) study eyes had a postoperative complication other than posterior capsule
      opacification compared with 18 of 116 (15.5%) controls (P = 0.07). CONCLUSIONS: A
      large proportion of patients with prior PPV obtain good visual acuity after
      phacoemulsification. We did not find significantly higher rates of intraoperative
      difficulties or postoperative complications compared with controls. The benefits
      of phacoemulsification seem to be limited only by retinal comorbidity.

PMID- 11986104
TI  - Comparison of iris-fixed Artisan lens implantation with excimer laser in situ
      keratomileusis in correcting myopia between -9.00 and -19.50 diopters: a
      randomized study.
AB  - OBJECTIVE: To compare Artisan lens implantation with laser in situ keratomileusis
      (LASIK) for the correction of myopia between -9.00 and -19.50 diopters. DESIGN:
      Prospective randomized clinical trial. PARTICIPANTS: Ninety eyes of 61
      consecutive patients were enrolled in the study. INTERVENTION: Forty-five eyes
      (50%) received Artisan lens, and 45 eyes (50%) received LASIK; the procedure
      assigned to each eye was randomized. Eighteen patients (29.5%) received Artisan
      lens in one eye and LASIK in the other. MAIN OUTCOME MEASURES: Slit-lamp
      microscopy, manifest refraction, uncorrected and spectacle-corrected visual
      acuity, contrast sensitivity, and specular microscopy were performed before
      surgery, and 1, 3, 6, and 12 months after surgery. Patient satisfaction and
      preference were assessed by a subjective questionnaire. RESULTS: At 1 year, 43
      eyes (95.6%) from the Artisan group and 41 eyes (91.1%) from the LASIK group were
      examined, the mean spherical equivalent refraction was -0.64 +/- 0.8 diopter in
      the Artisan eyes and -0.87 +/- 0.8 in the LASIK eyes. The uncorrected visual
      acuity was 20/20 or better in 9 Artisan eyes (20.9%) and 5 LASIK eyes (12.2%) and
      20/40 or better in 38 Artisan eyes (88.4%) and 24 LASIK eyes (58.5%); no Artisan
      eyes and 5 LASIK eyes (12.2%) lost 2 or more Snellen lines of spectacle-corrected
      visual acuity. One Artisan eye (2.3%) and six LASIK eyes (14.6%) reported severe
      night glare; the Artisan lens was exchanged with a larger optic diameter lens.
      Mean endothelial cell loss at 1 year was 0.7 +/- 1.1 cells/mm(2) in the Artisan
      eyes and 0.3 +/- 0.9 cells/mm(2) in the LASIK eyes. Contrast sensitivity curve
      decreased by 2 or more lines in two Artisan (4.7%) and six LASIK eyes (14.6%). Of
      the 18 patients who received both surgeries, one in each eye, 13 patients (72.2%)
      preferred the Artisan procedure because of the better quality of vision.
      CONCLUSIONS: In this study, Artisan lens implantation and LASIK were found to be
      similarly effective, stable, and reasonably safe for the correction of myopia
      between -9.00 and -19.50 diopters. Better uncorrected and spectacle-corrected
      visual acuity and contrast sensitivity, a lower enhancement rate, and
      exchangeability are the main advantages of Artisan lens implantation. Thirteen
      (72.2%) of the 18 patients who received the Artisan lens in one eye and LASIK in
      the other preferred the Artisan lens to the LASIK, mainly because of the better
      quality of vision.

PMID- 11986105
TI  - Tracker-assisted laser in situ keratomileusis for myopia using the autonomous
      scanning and tracking laser: 12-month results.
AB  - OBJECTIVE: To determine the safety, efficacy, and predictability of the
      Autonomous scanning and tracking laser for the correction of myopia and myopic
      astigmatism with laser in situ keratomileusis (LASIK) procedure. DESIGN:
      Retrospective, noncomparative case series. PARTICIPANTS: The first 129
      consecutive eyes with up to -13.00 diopters (D) of myopia and -5.00 D of
      astigmatism. INTERVENTION: Myopic tracker-assisted LASIK (T-LASIK) using the
      Autonomous Laser (Alcon Summit Autonomous, Waltham, MA) and Hansatome
      microkeratome (Bausch & Lomb Surgical, Bracknell, England). MAIN OUTCOME
      MEASURES: Uncorrected visual acuity (UCVA), manifest spherical equivalent (MSE),
      best spectacle-corrected visual acuity (BSCVA), and complications were studied.
      RESULTS: At 12 months, the mean MSE was -0.02 +/- 1.01 D, with 79.1% of eyes
      within 0.5 D and 89.9% of eyes within 1 D of the intended correction. UCVA was
      20/20 or better in 71.4%, 20/25 or better in 78.5%, and 20/40 or better in 92.8%
      of eyes. Two eyes (1.6%) lost 2 lines and five eyes (3.8%) gained 2 lines of
      BSCVA. Sixteen eyes (12.4%) required retreatment to correct residual myopia or
      astigmatism. After retreatment, 14 of 16 eyes were within 0.5 D of emmetropia.
      Nine eyes (6.9%) had minor flap complications; two eyes (1.6%) had grade 2
      diffuse lamellar keratitis, of which one eye had associated peripheral flap melt.
      One eye showed slight decentration; this eye was rolling throughout the
      procedure. All eyes had some dryness, with 10% severe enough to require temporary
      punctual occlusion with plugs. CONCLUSIONS: T-LASIK for myopic astigmatism with
      the Autonomous Laser is relatively safe, effective, and predictable. The tracker
      seems to be effective, and the complications are relatively few. Retreatment
      rates are acceptable and can be performed safely and effectively to improve
      visual outcome. The outcomes are comparable with other published data.

PMID- 11986106
TI  - Optical low coherence reflectometry for noncontact measurements of flap thickness
      during laser in situ keratomileusis.
AB  - OBJECTIVE: There is growing evidence that iatrogenic keratectasia after laser in
      situ keratomileusis (LASIK) for high corrections occurs more frequently than
      initially assumed, and that it may result from larger variation in flap
      thickness. DESIGN: Consecutive noncomparative case series PARTICIPANTS: Thirty
      four patients who underwent LASIK for myopia and astigmatism (first treatment
      group) and 10 patients who received re-LASIK (retreatment group). METHODS:
      Central corneal thickness and thickness of the lamella during LASIK were
      determined by optical low coherence reflectometry (OLCR) and contact ultrasound
      pachymetry. MAIN OUTCOME MEASURES: Thickness of the flap and its standard
      deviation, as well as its correlation with age, sphere, cylinder, corneal
      thickness, intraocular pressure, and corneal refractive power (K-readings).
      RESULTS: The mean flap thickness of the first treatment group determined by OLCR
      was 130 +/- 29 microm; the 95 percentile was 169 microm and the 5 percentile was
      86 microm. The flap thickness was not correlated with any of the investigated
      demographic or refractive parameters. The mean flap thickness of the retreatment
      group was 152 +/- 14 microm; the 95 percentile was 175 microm and the 5
      percentile was 137 microm. Thus, the flap thickness of the retreatment group was
      significantly thicker compared with the first treatment group (P < 0.001).
      CONCLUSIONS: Optical low coherence reflectometry (OLCR) was shown to be an
      appropriate alternative to ultrasonic preoperative and intraoperative corneal
      pachymetry in laser assisted in situ keratomileusis. The lack of correlation
      between achieved flap thickness and preoperative clinical data, such as corneal
      thickness, corneal curvature, intraocular pressure, and refraction, emphasizes
      the importance of measuring flap thickness and corneal bed thickness during
      surgery.

PMID- 11986107
TI  - Reliability of proton and goldmann applanation tonometers in normal and
      postkeratoplasty eyes.
AB  - OBJECTIVE: To compare the reliability of intraocular pressure (IOP) measurements
      with the ProTon tonometer and the Goldmann applanation tonometer (GAT) in normal
      and post-penetrating keratoplasty (post-PK) eyes. DESIGN: Prospective,
      nonrandomized, comparative case series. PARTICIPANTS: Twenty-four individuals (48
      eyes) with no known ocular disorder and 59 patients (59 eyes) that had undergone
      penetrating keratoplasty (PK) were included in the normal and post-PK groups,
      respectively. METHODS: Three readings at 5-minute intervals each were obtained
      with GAT and ProTon in both the groups. Each reading with ProTon was a mean of
      five accepted readings with the highest accuracy (standard error of mean, <0.5
      mmHg). In post-PK eyes with more than 3.00 diopters of astigmatism or with
      irregular astigmatism, the mean of two readings taken with GAT in the steepest
      and flattest axis was considered to be the IOP. MAIN OUTCOME MEASURES: The IOP
      measurements in all groups were compared using a two-tail paired t test. The
      coefficient of repeatability and Cronbach's coefficient alpha were calculated
      separately for the IOP measured using both instruments in each group. RESULTS:
      There was no significant difference in the second (r1) and third (r2) IOP reading
      using the GAT and ProTon tonometers in normal and post-PK eyes. The coefficients
      of repeatability for GAT and ProTon were 2.64 and 2.49 in normal versus 3.72 and
      3.47 in the post-PK group. The Cronbach's alpha for GAT and ProTon was 0.94 and
      0.95 in the normal group versus 0.95 for both GAT and ProTon in the post-PK
      group. CONCLUSIONS: The results of our study show that the ProTon tonometer is
      reliable and comparable with GAT for recording IOP in normal and post-PK eyes.

PMID- 11986108
TI  - Delayed-onset bleb-associated endophthalmitis: clinical features and visual
      acuity outcomes.
AB  - OBJECTIVE: To investigate clinical factors, causative organisms, treatments, and
      visual acuity and intraocular pressure outcomes associated with delayed-onset,
      bleb-associated endophthalmitis. DESIGN: Retrospective, noncomparative,
      consecutive case series. PARTICIPANTS: All patients treated for bleb-associated
      endophthalmitis at Bascom Palmer Eye Institute between January 1, 1996, and July
      1, 2001. All patients had prior glaucoma filtering surgery. Patients with
      inadvertent functioning blebs after cataract extraction were excluded. MAIN
      OUTCOME MEASURES: Visual acuity outcomes and intraocular pressure control after
      endophthalmitis. RESULTS: An antifibrotic agent was used in 40 (82%) of the 49
      eyes identified, including mitomycin-C in 33 (67%) and 5-fluorouracil (5-FU) in 7
      (14%). The mean interval between the initial filtering surgery and
      endophthalmitis diagnosis was 5.0 years (range, 0.7-12.2 years). The mean follow
      up time after treatment for endophthalmitis was 6.9 months (range, 1-60 months).
      As recorded in the medical record, potential risk factors and clinical features
      among the study population included history of bleb leak in 13 (27%) eyes, bleb
      manipulations in 15 (31%) (needling in 3 [6%], compression sutures in 2 [4%],
      laser suture lysis in 6 [12%], bleb revision in 5 [10%], and autologous blood
      injection in 2 [4%]), bleb defects in 6 (12%), inferior bleb location 6 (12%),
      and nasolacrimal duct obstruction in 1 (2%). The most common causative organisms
      were Streptococcus species in 15 eyes (31%) and Staphylococcus species in 11 eyes
      (22%). Final visual acuities in the vitrectomy group (n = 22) versus the initial
      tap group (n = 26) were as follows: > or = 20/40 (5% versus 15%), 20/50 to 20/400
      (32% versus 54%), and < 5/200 (64% versus 31%). Eleven (22%) patients eventually
      underwent enucleation or evisceration secondary to pain and/or poor vision (light
      perception to no light perception). In 4 (11%) of the 38 eyes not enucleated,
      intraocular pressures were poorly controlled at last follow-up (>21 mmHg) after
      treatment of endophthalmitis. CONCLUSIONS: Streptococcus species and
      Staphylococcus species were the most common causative organisms in the current
      series of patients with delayed-onset bleb-associated endophthalmitis. Despite
      successful treatment of the infection, visual outcomes are generally poor.

PMID- 11986109
TI  - Trabeculectomies in fellow eyes have an increased risk of tenon's capsule cysts.
AB  - OBJECTIVE: To assess outcomes and complications of primary trabeculectomies in
      fellow eyes in a large group of patients. The assumption was that first and
      fellow eyes undergoing fistulizing surgical procedures behave similarly in the
      postoperative period. DESIGN: Retrospective nonrandomized comparative trial
      (paired eye study). PARTICIPANTS: Over a 4-year period, 566 consecutive patients
      underwent primary trabeculectomy, all without antifibrotic agents. One hundred
      thirty-eight of these patients underwent bilateral surgery. INTERVENTION: A
      primary trabeculectomy was performed. MAIN OUTCOME MEASURES: Preoperative data,
      postoperative intraocular pressure, and visual acuity were monitored. In
      addition, complications and the need for consecutive surgical procedures were
      noted. RESULTS: The mean follow-up period of these trabeculectomies was 27.4
      months (range, 7-62 months). Of the 124 bilateral adult cases, no statistical
      difference was found in intraocular pressures, number of antiglaucomatous
      medications, and success or failure rates between the two eyes. The need for
      enhancement procedures, such as needling or surgical excision of Tenon's capsule
      cysts, was significantly higher in fellow eyes than in first eyes (16 vs. 6
      cases; P = 0.03; Mann-Whitney U test). Hypotony as a complication occurred more
      frequently in fellow eyes. CONCLUSIONS: Primary trabeculectomies performed in
      both eyes of patients have a remarkably similar clinical course. Failures of
      first eyes may be a reason to use antimetabolites in primary trabeculectomy of
      the fellow eye. The present data suggest that fellow eyes have a greater risk of
      Tenon's capsule cyst formation. This may be important for patient counseling
      before surgery. These results may additionally be important for clinical studies.
      Given that first and fellow eyes do not behave in an absolutely similar manner,
      study designs making intraindividual comparisons may not be feasible.

PMID- 11986111
TI  - Short wavelength automated perimetry, frequency doubling technology perimetry,
      and pattern electroretinography for prediction of progressive glaucomatous
      standard visual field defects.
AB  - PURPOSE: To evaluate the clinical use of a test battery of short wavelength
      automated perimetry (SWAP), frequency doubling technology perimetry (FDT), and
      pattern electroretinography (PERG) in predicting progressive glaucomatous visual
      field defects on standard automated perimetry (SAP). STUDY DESIGN: A prospective,
      longitudinal, observational case series. PARTICIPANTS: One hundred and fifty-two
      patients with primary open-angle glaucoma (POAG) with bilateral glaucomatous
      visual field defects on SAP were followed at 6-month intervals over a period of
      30 months. MAIN OUTCOME MEASURES: Short wavelength automated perimetry, FDT, and
      PERG results were compared between POAG eyes with and without progressive field
      loss on SAP. These two groups were used to evaluate whether PERG, SWAP, and/or
      FDT is predictive of future progression of field loss on SAP. RESULTS: Using the
      criteria of progressive field loss on SAP defined by the Collaborative Normal
      Tension Glaucoma Study, 54 eyes (study group) of 54 POAG patients showed
      progressive defects, whereas 84 eyes (control group) of 84 POAG patients showed
      no progression. Only 11.1% (6 of 54) of the eyes with a progression of field loss
      on SAP showed no increase of deficits on the three functional tests before
      progression. Short wavelength automated perimetry detected early progressive
      defects on SAP in 43 of the 54 eyes (79.6%). Of these 54 POAG eyes, FDT showed
      progressive deficits in 40 eyes (74.1%), whereas PERG amplitude P1N2 showed
      progressive deficits in 35 eyes (64.8%) before progression of field loss on SAP.
      A test battery consisting of SWAP and PERG P1N2-amplitude was able to detect
      88.9% of eyes before a prediction of field loss on SAP. When comparing the
      results of the two functional tests, SWAP and FDT in the 84 eyes without
      progression of field loss on SAP between baseline and at 30 months, SWAP and FDT
      showed progressive deficits in 34.5% and 35.7%, respectively. CONCLUSIONS: All
      three tests (SWAP, FDT, and PERG) have been successful in detecting glaucoma eyes
      with a future progression of standard visual field defects. A test battery of
      SWAP and PERG P1N2-amplitude improved the power to predict these progressive
      defects on SAP. It remains to be seen whether the long-term follow-up in POAG
      eyes will improve the false-positive rate of SWAP and FDT.

PMID- 11986110
TI  - Comparison of travoprost 0.0015% and 0.004% with timolol 0.5% in patients with
      elevated intraocular pressure: a 6-month, masked, multicenter trial.
AB  - OBJECTIVE: To compare the safety and intraocular pressure (IOP)-lowering efficacy
      of once-daily travoprost (0.0015% and 0.004%) to twice-daily timolol 0.5%.
      DESIGN: Prospective, 6-month, randomized, controlled, multicenter, double-masked,
      phase III study. PARTICIPANTS: Six hundred five patients with open-angle glaucoma
      or ocular hypertension. METHODS: Patients with an 8 AM IOP between 24 to 36 mmHg
      in at least one eye (the same eye) at two eligibility visits received either
      travoprost 0.0015%, travoprost 0.004% (dosed every day), or timolol 0.5% (dosed
      twice daily). MAIN OUTCOME MEASURES: Mean IOP at 8 AM, 10 AM, and 4 PM in the
      patient's eye with the higher baseline IOP. RESULTS: The mean IOP was
      significantly lower for both concentrations of travoprost compared with timolol.
      Travoprost was statistically superior to timolol at 9 of 13 visits, with
      differences in IOP reductions ranging from 0.9 to 1.8 mmHg (0.0015%) and 10 of 13
      visits with differences in IOP reductions from 0.9 to 2.4 mmHg (0.004%). Mean IOP
      changes from baseline ranged from -6.0 to -7.5 mmHg (0.0015%), -6.5 to -8.0 mmHg
      (0.004%), and -5.2 to -7.0 mmHg for timolol. Hyperemia was experienced at rates
      of 29.2% (59 of 202) for travoprost 0.0015%, 42.8% (86 of 201) for travoprost
      0.004%, and 8.9% (18 of 202) for timolol. Iris pigmentation changes were observed
      in 1.0% (2 of 200) of patients receiving travoprost 0.004% with no changes noted
      in the travoprost 0.0015% group or the timolol group. A decrease in pulse and
      systolic blood pressure was observed in the timolol group. There were no other
      clinically relevant or statistically significant changes from baseline in ocular
      signs or laboratory values, and no serious, related, unexpected adverse events
      were reported for any group. CONCLUSIONS: Travoprost (0.0015% and 0.004%), dosed
      once daily in the evening, is statistically superior or equal to timolol 0.5%
      dosed twice daily at all treatment visits during this 6-month study. IOP
      reductions of up to 2.0 mmHg greater than timolol were found in the travoprost
      0.004% pooled data group. Travoprost is safe and well tolerated in patients with
      open-angle glaucoma or ocular hypertension.

PMID- 11986112
TI  - Depression in patients with glaucoma as measured by self-report surveys.
AB  - PURPOSE: This study aimed to determine whether patients with glaucoma have more
      depressive symptoms than patients without glaucoma. DESIGN: Prospective case
      control study. PARTICIPANTS: The study population was recruited from two
      university-based glaucoma clinical practices and a university-based general
      ophthalmology clinic and consisted of 121 patients with open-angle glaucoma, 42
      with diagnoses of suspected glaucoma, and 135 with no chronic ocular conditions
      except cataract. INTERVENTION: The Center for Epidemiologic Studies Depression
      Scale (CES-D) and Composite International Diagnostic Interview, Short Form (CIDI
      SF) questionnaires were administered to all subjects. Demographic information,
      medical history, and responses to the questionnaires were elicited by an
      interviewer. Medical record review was performed to obtain clinical examination
      data and to substantiate the medical and demographic data obtained by the
      interviewer. MAIN OUTCOME MEASURES: The questionnaire scores by diagnostic group,
      demographic characteristics, and medical history were examined. Secondary outcome
      measures were questionnaire scores in patients with glaucoma by visual impairment
      and glaucoma medication use. RESULTS: Depression scores for patients with
      glaucoma did not differ significantly from scores of control patients. Having
      past or present mental illness was the only consistent predictor for depression
      in both questionnaires. Among glaucoma patients, visual acuity level, visual
      field severity, and use of topical beta-blockers were not predictors for
      depression. CONCLUSIONS: Patients with glaucoma do not report being more
      depressed than patients without glaucoma as measured by the CES-D and the CIDI-SF
      questionnaires.

PMID- 11986113
TI  - Management of myogenic ptosis.
AB  - OBJECTIVE: To review the genetics, clinical features, and management of patients
      affected by myogenic ptosis. DESIGN: Retrospective, noncomparative interventional
      case series. PARTICIPANTS: Twenty-eight patients with myogenic ptosis. METHODS: A
      review of all patients with myogenic ptosis between 1992 and 2000 was made in a
      tertiary oculoplastics practice. MAIN OUTCOME MEASURES: Ocular and systemic
      findings associated with myogenic ptosis were examined. Patients were diagnosed
      clinically, and ancillary tests (including genetic tests and muscle biopsy
      histologic findings) were reviewed. Surgical management principles and
      complications are discussed. RESULTS: Most of our ptosis patients had chronic
      progressive external ophthalmoplegia (43%), oculopharyngeal muscular dystrophy
      (OPMD; 18%), and myotonic dystrophy (18%). Fifty percent of myogenic ptosis
      patients in our series underwent frontalis suspensions. Twenty-one percent of
      patients who initially had operations at our institution had minor complications,
      most related to corneal exposure. The most common ocular finding other than
      ptosis and ophthalmoplegia was pigmentary retinopathy (25%). The most common
      systemic finding in our patients was dysphagia (43%). Genetic testing for OPMD
      was highly sensitive. Muscle biopsy results for mitochondrial myopathies were
      less accurate as adjunctive diagnostic tests. CONCLUSIONS: Myogenic ptosis should
      be considered in the differential diagnosis of any atypical ptosis presentation.
      To avoid complications, surgery should be performed only when the visual axis is
      obscured. We recommend the use of silicone slings in any patient with severe
      ptosis and less than 8 mm of levator function. Genetic testing of patients with
      myogenic ptosis is important to allow accurate diagnosis and to permit
      appropriate counseling on potentially life-threatening health issues.

PMID- 11986114
TI  - Darkness and near work: myopia and its progression in third-year law students.
AB  - PURPOSE: To evaluate myopia prevalence, myopia progression, and various potential
      myopia risk factors in third-year law students. DESIGN: Cross-sectional study and
      survey. PARTICIPANTS: One hundred seventy-nine third-year law students at the
      University of Pennsylvania. METHODS: We administered a questionnaire to assess
      the prevalence of myopia, myopia progression, and risk factors, including near
      work, family history, and daily light/dark exposure. We conducted a screening eye
      examination to ascertain myopia status. Myopia was defined as the mean spherical
      equivalent of the two eyes of </=-0.5 diopters; myopia progression was defined by
      the self-reported need for a stronger eyeglass prescription during law school.
      MAIN OUTCOME MEASURES: (1) prevalence of myopia, (2) progression of myopia.
      RESULTS: Seventy-nine percent of the class participated (n = 179, two were
      excluded for amblyopia leaving 177 students). Fifty-eight percent were male, 75%
      were Caucasian, and the mean age was 27 years. Seventy-nine percent reported
      parental myopia. The mean amount of near work was 7.4 hours/day; mean sleep was
      7.9 hours/day; mean darkness was 5.3 hours/day. Sixty-six percent of the students
      were myopic. Of 96 participants myopic before law school, myopia increased in 83
      (86%) during law school. Among 75 students not myopic at the beginning of law
      school, 14 (19%) became myopic. The onset of myopia could not be determined for 6
      patients. There were trends for higher myopia prevalence among those with a
      parental myopia history (P = 0.14) and for increased myopia progression among
      those reporting more daily near work (P = 0.18). Students with </=5.6 hours of
      daily darkness were more likely to report myopia progression than those with >5.6
      hours of darkness per day (95% vs. 80%, P = 0.07). To account for possible
      confounding effects of risk factors with myopia progression, logistic regression
      with categorization of the continuous exposure variables (hours of near work,
      sleep, and darkness) above or below median values weakened the near work
      association (odds ratio 1.8, 95% confidence interval 0.5-6.7, P = 0.35) but
      continued to identify darkness association with daily hours of darkness (odds
      ratio 4.8, 95% confidence interval 1.0 >/= 23.3, P < 0.05). Among the 77 students
      with myopia onset before college, those with </=5.6 hours of daily darkness were
      more likely to progress than those with more hours of daily darkness (97% vs.
      76%, P = 0.01). CONCLUSIONS: This study confirms high rates of myopia prevalence
      and myopia progression among law students. The strongest association, especially
      in those with myopia onset before college, was a relation of myopia progression
      during law school with less daily exposure to darkness, a potential risk factor
      previously identified in childhood myopia. The role of exposure to darkness in
      refractive development warrants additional study.

PMID- 11986117
TI  - EMRA's policy on unsupervised resident moonlighting: a time to refocus, indeed.

PMID- 11986118
TI  - Functional imaging is fulfilling some promises.

PMID- 11986119
TI  - The integration of neurology, psychiatry, and neuroscience in the 21st century.
AB  - OBJECTIVE: This article examines the historical basis for the divergence of
      neurology and psychiatry over the past century and discusses prospects for a
      rapprochement and potential convergence of the two specialties in the next
      century. METHOD: The author presents a brief historical overview of developments
      in neurology and psychiatry from the late 19th century. The histories of research
      and prevailing scientific opinion on two neuropsychiatric disorders, Alzheimer's
      disease and Tourette's syndrome, are compared to illustrate the effects of
      viewing a disease process from, respectively, the neurologic/organic and
      psychiatric/functional perspectives. RESULTS: Research on Alzheimer's disease,
      because of its early pathologic demonstration, moved rapidly toward
      identification of associated synaptic abnormalities and genetic mutations. In
      Tourette's syndrome, the absence of evident brain pathology resulted in
      vacillation between organic and functional explanations and persistent
      controversy about the nature of the illness. CONCLUSIONS: Neurology and
      psychiatry have, for much of the past century, been separated by an artificial
      wall created by the divergence of their philosophical approaches and research and
      treatment methods. Scientific advances in recent decades have made it clear that
      this separation is arbitrary and counterproductive. Neurologic and psychiatric
      research are moving closer together in the tools they use, the questions they
      ask, and the theoretical frameworks they employ. The interests of neurology and
      psychiatry converge within the framework of modern neuroscience. Further progress
      in understanding brain diseases and behavior demands fuller collaboration and
      integration of these fields. Leaders in academic medicine and science must work
      to break down the barriers between disciplines.

PMID- 11986120
TI  - Informed consent and the capacity for voluntarism.
AB  - OBJECTIVE: Informed consent is built upon the elements of information, decisional
      capacity, and volunteerism. Of these elements, voluntarism in clinical and
      research consent is the least well understood. This has interfered with the
      ability to resolve key ethical problems faced by the field of psychiatry. METHOD:
      The author suggests that voluntarism encompasses an individual's ability to act
      in accordance with one's authentic sense of what is good, right, and best in
      light of one's situation, values, and prior history. Voluntarism further entails
      the capacity to make this choice freely and in the absence of coercion.
      Deliberateness, purposefulness of intent, clarity, genuineness, and coherence
      with prior life decisions are implicitly emphasized in this construction.
      RESULTS: The author offers and illustrates a framework for voluntarism in
      clinical and research consent decisions, focusing on four domains of potential
      influence: 1) developmental factors, 2) illness-related considerations, 3)
      psychological issues and cultural and religious values, and 4) external features
      and pressures. CONCLUSIONS: It is hoped that improved understanding of
      voluntarism will help in our efforts to fulfill the principle of respect for
      persons in clinical care and research.

PMID- 11986121
TI  - Schizophrenia: reproductive hormones and the brain.
AB  - OBJECTIVE: Onset of schizophrenia occurs during the reproductive period in more
      than 80% of those affected. The author reviews neuroendocrine and physiologic
      events that occur in the basal forebrain at the initiation of and throughout the
      reproductive period and proposes their possible relationship to the onset of
      schizophrenia. METHOD: The neuroendocrine changes that occur in specific areas of
      the anterior basal forebrain during the reproductive period are reviewed and
      analyzed in relation to reported anatomic, molecular, and biochemical pathologies
      of schizophrenia. RESULTS: The reproductive period is associated with development
      of regular pulsatile release in the brain and bloodstream of gonadotropic
      releasing hormones from the hypothalamus, luteinizing and follicle stimulating
      hormones from the pituitary, and gonadal hormones from the ovaries and testes. In
      addition to being concentrated in the hypothalamus, brain receptors for
      gonadotropic and gonadal hormones are concentrated in specific subcortical
      forebrain nuclei of the limbic system that project to the thalamus and to
      cortical and subcortical structures that subserve perception, cognition, and
      behavior. CONCLUSIONS: There is a flood of estrogen and testosterone to the brain
      and body during puberty and throughout the reproductive period. To avoid
      hyperexcitability and seizures, the surge of these excitatory hormones must be
      counterbalanced by appropriate inhibitory factors. Excessive focal inhibition may
      be induced by increased release of or increased receptors for one or more
      inhibitory transmitters, e.g., dopamine, serotonin, and gamma-aminobutyric acid
      in the anterior basal forebrain. Further investigation of the physiology and
      pathology of this brain region, where abnormal electrical activity was recorded
      from individuals with schizophrenia many years ago and where dopamine D(2) and
      dopamine D(3) receptors targeted by the most effective antipsychotic agents are
      maximally expressed, could lead to greater understanding of the critical
      pathophysiology for development of schizophrenia.

PMID- 11986122
TI  - The human genome: gene silencing.

PMID- 11986123
TI  - Creating a psychodynamic formulation from a clinical evaluation.

PMID- 11986125
TI  - The functional neuroanatomy of the placebo effect.
AB  - OBJECTIVE: Administration of placebo can result in a clinical response
      indistinguishable from that seen with active antidepressant treatment. Functional
      brain correlates of this phenomenon have not been fully characterized. METHOD:
      Changes in brain glucose metabolism were measured by using positron emission
      tomography in hospitalized men with unipolar depression who were administered
      placebo as part of an inpatient imaging study of fluoxetine. Common and unique
      response effects to administration of placebo or fluoxetine were assessed after a
      6-week, double-blind trial. RESULTS: Placebo response was associated with
      regional metabolic increases involving the prefrontal, anterior cingulate,
      premotor, parietal, posterior insula, and posterior cingulate and metabolic
      decreases involving the subgenual cingulate, parahippocampus, and thalamus.
      Regions of change overlapped those seen in responders administered active
      fluoxetine. Fluoxetine response, however, was associated with additional
      subcortical and limbic changes in the brainstem, striatum, anterior insula, and
      hippocampus, sources of efferent input to the response-specific regions
      identified with both agents. CONCLUSIONS: The common pattern of cortical glucose
      metabolism increases and limbic-paralimbic metabolism decreases in placebo and
      fluoxetine responders suggests that facilitation of these changes may be
      necessary for depression remission, regardless of treatment modality. Clinical
      improvement in the group receiving placebo as part of an inpatient study is
      consistent with the well-recognized effect that altering the therapeutic
      environment may significantly contribute to reducing clinical symptoms. The
      additional subcortical and limbic metabolism decreases seen uniquely in
      fluoxetine responders may convey additional advantage in maintaining long-term
      clinical response and in relapse prevention.

PMID- 11986126
TI  - Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A
      Potential Outcome Measure in Alzheimer's Disease Treatment Studies.
AB  - OBJECTIVE: It is well established that regional cerebral metabolic rates for
      glucose assessed by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography
      (PET) in patients with Alzheimer's disease in the mental resting state (eyes and
      ears covered) provide a sensitive, in vivo metabolic index of Alzheimer's disease
      dementia. Few studies, however, have evaluated longitudinal declines in regional
      cerebral glucose metabolism in patients with dementia caused by Alzheimer's
      disease. In addition, the available studies have not used recently developed
      brain mapping algorithms to characterize the progression of Alzheimer's disease
      throughout the brain, and none considered the statistical power of regional
      cerebral glucose metabolism in testing the ability of treatments to attenuate the
      progression of dementia. METHOD: The authors used FDG PET and a brain mapping
      algorithm to investigate cross-sectional reductions in regional cerebral glucose
      metabolism, longitudinal decline in regional cerebral glucose metabolism after a
      1-year follow-up, and the power of this method to evaluate treatments for
      Alzheimer's disease in patients with mild to moderate dementia. PET scans were
      initially acquired in 14 patients with Alzheimer's disease and 34 healthy
      comparison subjects of similar age and sex. Repeat scans were obtained in the
      patients 1 year later. Power analyses for voxels showing maximal decline over the
      1-year period in regional cerebral glucose metabolism (mg/100 g per minute) were
      computed to estimate the sample sizes needed to detect a significant treatment
      response in a 1-year, double-blind, placebo-controlled treatment study. RESULTS:
      The patients with Alzheimer's disease had significantly lower glucose metabolism
      than healthy comparison subjects in parietal, temporal, occipital, frontal, and
      posterior cingulate cortices. One year later, the patients with Alzheimer's
      disease had significant declines in glucose metabolism in parietal, temporal,
      frontal, and posterior cingulate cortices. Using maximal glucose metabolism
      reductions in the left frontal cortex, we estimated that as few as 36 patients
      per group would be needed to detect a 33% treatment response with one-tailed
      significance of p</=0.005 and 80% power in a 1-year, double-blind, placebo
      controlled treatment study. CONCLUSIONS: These findings indicate that brain
      metabolism as assessed by FDG PET during mental rest is a sensitive marker of
      disease progression in Alzheimer's disease over a 1-year period. These findings
      also support the feasibility of using FDG PET as an outcome measure to test the
      ability of treatments to attenuate the progression of Alzheimer's disease.

PMID- 11986127
TI  - Relationships among the metabolic patterns that correlate with mnemonic,
      visuospatial, and mood symptoms in Parkinson's disease.
AB  - OBJECTIVE: A multivariate analysis of baseline brain metabolism was used to
      investigate the relationships among pathophysiological mechanisms responsible for
      cognitive dysfunction and dysphoria in nondemented patients with Parkinson's
      disease. METHOD: Using [(18)F]fluorodeoxyglucose positron emission tomography and
      neuropsychological tests, the authors studied 15 nondemented patients who had
      Parkinson's disease without major depression (DSM-III-R). Their mean age was 59.2
      years (SD=9.2), the mean rating of Parkinson's disease stage (Hoehn and Yahr
      scale) was 3.3 (SD=0.9), and all had Mini-Mental State Examination scores of 24
      or higher. To identify specific regional patterns of brain metabolism associated
      with abnormal cognitive and mood functioning, the data were analyzed by using
      brain-behavior partial least squares. This multivariate voxel-based analysis
      allowed detection of significant topographic patterns of metabolic activity and
      quantification of the extent to which each topographic pattern correlated with
      scores on mnemonic, visuospatial, and dysphoric tests. RESULTS: Two significant,
      independent topographic patterns were identified. Pattern 1 included parieto
      occipito-temporal and medial temporal brain regions, and pattern 2 included the
      lateral frontal and anterior limbic cortex. Patterns 1 and 2 exhibited a double
      dissociation in their behavioral correlates: pattern 1 correlated with both
      visuospatial and mnemonic functioning but not with dysphoria; pattern 2
      correlated with dysphoria but not with the cognitive measures. CONCLUSIONS: The
      authors used the independence of topographic patterns and the size of
      correlations between topographic patterns and behavior to infer relationships
      among the pathophysiological processes responsible for the correlations. The
      finding that mildly abnormal mnemonic and visuospatial functioning correlated
      with the same topographic pattern suggests that a common pathophysiology
      underlies this marker of cognition in Parkinson's disease. By contrast, the
      independence of the two topographic patterns supports the notion that different
      mechanisms underlie cognitive and dysphoric symptoms in nondemented patients with
      Parkinson's disease.

PMID- 11986128
TI  - Fluorine magnetic resonance spectroscopy measurement of brain fluvoxamine and
      fluoxetine in pediatric patients treated for pervasive developmental disorders.
AB  - OBJECTIVE: Pediatric populations, including those with autistic disorder or other
      pervasive developmental disorders, increasingly are being prescribed selective
      serotonin reuptake inhibitors (SSRIs). Little is known about the age-related
      brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing
      of medications for children. The authors used fluorine magnetic resonance
      spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of
      fluvoxamine and fluoxetine in children taking SSRIs. METHOD: Twenty-one pediatric
      subjects with diagnoses of autistic disorder or other pervasive developmental
      disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or
      fluoxetine, were recruited for the study; 16 successfully completed the imaging
      protocol. Whole-brain drug levels in this group were compared to similarly
      acquired data from 28 adults. RESULTS: A significant relationship between dose
      and brain drug concentration was observed for both drugs across the age range
      studied. Brain fluvoxamine concentration in the children was lower, consistent
      with a lower dose/body mass drug prescription; when brain concentration was
      adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine
      concentration was similar between age groups; no significant age effects on brain
      fluoxetine drug levels remained after adjustment for dose/mass. Observations of
      brain fluoxetine bioavailability and elimination half-life also were similar
      between age groups. CONCLUSIONS: These findings suggest that fluvoxamine or
      fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment
      approach for medicating children with autistic disorder or other pervasive
      developmental disorders. It must be determined whether these findings can be
      generalized to other pediatric populations.

PMID- 11986129
TI  - PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with
      schizophrenia.
AB  - OBJECTIVE: Postmortem studies and a positron emission tomography (PET) study have
      suggested that there is a disturbance of central D(1) dopamine receptor function
      in schizophrenia. The objective of the present PET study was to compare D(1)
      receptor binding in first-admission, neuroleptic-naive patients with
      schizophrenia and in healthy subjects. METHOD: Ten healthy comparison subjects
      and 10 neuroleptic-naive patients with schizophrenia (diagnosed according to DSM
      III-R) were examined twice by PET using (11)C-labeled SCH 23390 ([(11)C]SCH
      23390) with high and low specific radioactivity, respectively. The binding
      potential, receptor density (B(max)), and affinity (K(d)) were determined for the
      caudate nucleus, the putamen, and several neocortical regions during both PET
      examinations. Scatchard plots from the two measurements were used to calculate
      regional D(1) B(max) and K(d). The regional binding values were tested for
      hemispheric asymmetry and for correlation to clinical symptoms measured by the
      Brief Psychiatric Rating Scale (BPRS). RESULTS: [(11)C]SCH 23390 binding to D(1)
      receptors did not differ significantly between subjects with schizophrenia and
      healthy subjects in any of the brain regions or for any of the binding measures
      studied. Asymmetry of the regional binding values did not differ significantly
      between the two groups. Scores on the BPRS negative symptom subscale correlated
      significantly with the B(max) in the right frontal cortex. CONCLUSIONS: These
      results do not replicate previous postmortem and PET findings of altered central
      dopamine D(1) receptor binding in schizophrenia. The finding of a positive
      correlation between frontal D(1) binding and scores on the negative symptom
      subscale of the BPRS is contrary to a previously reported finding of a negative
      correlation. These discrepancies motivate further studies using D(1) ligands with
      higher signals for cortical regions.

PMID- 11986130
TI  - PET study of [(18)F]6-fluoro-L-dopa uptake in neuroleptic- and mood-stabilizer
      naive first-episode nonpsychotic mania: effects of treatment with divalproex
      sodium.
AB  - OBJECTIVE: Although dopaminergic hyperactivity has been implicated in mania, the
      precise location in the brain of the abnormality is unclear. This study assessed
      presynaptic dopamine function in neuroleptic- and mood-stabilizer-naive
      nonpsychotic first-episode manic patients before and after treatment with
      divalproex sodium by measuring [(18)F]6-fluoro-L-dopa ([(18)F]DOPA) uptake in the
      striatum with positron emission tomography (PET). METHOD: Thirteen patients with
      DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects
      underwent [(18)F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6
      weeks after beginning treatment with divalproex sodium monotherapy. [(18)F]DOPA
      uptake rate constants (K(i) values) in the striatum were calculated by using
      graphical analysis with activity from the occipital cortex as the input function.
      RESULTS: No significant differences in [(18)F]DOPA uptake rate constants in the
      striatum were found between the manic patients and the comparison subjects. After
      treatment with divalproex sodium, [(18)F]DOPA rate constants were significantly
      reduced in the patients and were lower in the patients than in the comparison
      subjects. CONCLUSIONS: Although presynaptic dopamine function as reflected by
      [(18)F]DOPA uptake is not altered in mania, presynaptic dopamine function in
      manic patients was lower after treatment with divalproex sodium.

PMID- 11986131
TI  - Validity of controlled clinical trials of psychotherapy: findings from the NIMH
      Treatment of Depression Collaborative Research Program.
AB  - OBJECTIVE: This research extends a series of studies that have examined the
      process of psychotherapy. The authors hypothesized that manual regimens of
      psychotherapy compared in a controlled clinical trial would overlap considerably
      in process and technique and that intervention strategies common to both
      treatments would be responsible for promoting patient change. METHOD: Expert
      therapists developed prototypes of the ideal regimens of brief interpersonal
      psychotherapy and cognitive behavior therapy using the Psychotherapy Process Q
      Set, an instrument designed to provide a standard language for describing
      treatment processes. A separate set of clinical judges then used the
      Psychotherapy Process Q-Set to score the actual transcripts of interpersonal
      psychotherapy and cognitive behavior therapy sessions conducted as part of the
      NIMH Treatment of Depression Collaborative Research Program. The expert
      prototypes were then compared with actual therapy administered in order to
      determine the extent to which each form of therapy conformed to its ideal
      prototype. RESULTS: Both the interpersonal psychotherapy and cognitive behavior
      therapy sessions adhered most strongly to the ideal prototype of cognitive
      behavior therapy. In addition, adherence to the cognitive behavior therapy
      prototype yielded more positive correlations with outcome measures across both
      types of treatment. CONCLUSIONS: Relying on brand names of therapy can be
      misleading. These findings suggest that the basic premise of controlled clinical
      trials (i.e., that the compared interventions represent separate and distinct
      treatments) may not have been met in the NIMH Treatment of Depression
      Collaborative Research Program. The implications of these findings for using
      controlled clinical trials to study psychotherapy are discussed.

PMID- 11986132
TI  - Characterizing affective instability in borderline personality disorder.
AB  - OBJECTIVE: This study sought to understand affective instability among patients
      with borderline personality disorder by examining the degree of instability in
      six affective domains. The authors also examined the subjective intensity with
      which moods are experienced and the association between instability and intensity
      of affect. METHOD: In a group of 152 patients with personality disorders,
      subjective affective intensity and six dimensions of affective instability were
      measured. The mean scores for lability and intensity for each affective domain
      for patients with borderline personality disorder were compared with those of
      patients with other personality disorders through analyses that controlled for
      other axis I affective disorders, age, and sex. RESULTS: Greater lability in
      terms of anger and anxiety and oscillation between depression and anxiety, but
      not in terms of oscillation between depression and elation, was associated with
      borderline personality disorder. Contrary to expectation, the experience of an
      increase in subjective affective intensity was not more prominent in patients
      with borderline personality disorder than in those with other personality
      disorders. CONCLUSIONS: By applying a finer-grained perspective on affective
      instability than those of previous personality disorder studies, this study
      points to patterns of affective experience characteristic of patients with
      borderline personality disorder.

PMID- 11986133
TI  - Depressive and anxiety disorders in women with HIV infection.
AB  - OBJECTIVE: This study examined whether there were differences in the rate of
      depressive and anxiety disorders between HIV-infected women (N=93) and a
      comparison group of uninfected women (N=62). Secondary objectives were to examine
      correlates of depression in HIV-infected women-including HIV disease stage and
      protease inhibitor use-and the associations between symptoms of depression or
      anxiety and other potential predictor variables. METHOD: Subjects underwent
      extensive semiannual clinical, psychiatric, neuropsychological, and immunological
      evaluations. Depressive and anxiety disorder diagnoses were assessed by using the
      Structured Clinical Interview for DSM-IV. Symptoms of depression and anxiety were
      evaluated with the Hamilton Depression Rating Scale (the 17-item version and a
      modified 11-item version) and the Hamilton Anxiety Rating Scale, respectively.
      RESULTS: The rate of current major depressive disorder was four times higher in
      HIV-seropositive women (19.4%) than in HIV-seronegative women (4.8%). Mean
      depressive symptom scores on the 17-item Hamilton depression scale also were
      significantly higher, overall, in the HIV-infected women (mean=8.7, SD=8.0)
      relative to comparison subjects (mean=3.3, SD=5.8). There was no significant
      between-group difference in the rate of anxiety disorders. However, HIV
      seropositive women had significantly higher anxiety symptom scores (mean=8.8,
      SD=8.9) than did HIV-seronegative women (mean=3.6, SD=5.5). Both groups had
      similar substance abuse/dependence histories, but adjusting for this factor had
      little impact on the relationship of HIV status to current major depressive
      disorder. CONCLUSIONS: HIV-seropositive women without current substance abuse
      exhibited a significantly higher rate of major depressive disorder and more
      symptoms of depression and anxiety than did a group of HIV-seronegative women
      with similar demographic characteristics. These controlled, clinical findings
      extend recent epidemiologic findings and underscore the importance of adequate
      assessment and treatment of depression and anxiety in HIV-infected women.

PMID- 11986134
TI  - Impaired decision-making ability in subjects with Alzheimer's disease and
      willingness to participate in research.
AB  - OBJECTIVE: Ethical concerns persist over research participation of decisionally
      impaired persons, such as those suffering from Alzheimer's disease. Such persons
      may be poor judges of the burdens and risks of specific research protocols. Since
      even decisionally incapacitated persons cannot be enrolled in studies against
      their objection, their preferences convey important ethical information. The
      authors examined the effects of cognitive and decisional impairment on
      willingness to participate in research among persons with Alzheimer's disease.
      METHOD: Cognitive status, decision-making ability, and willingness to participate
      in four hypothetical research protocols of varying risk/benefit profiles were
      measured in 34 subjects with mild to mild/moderate Alzheimer's disease and 14
      healthy elderly comparison subjects. Univariate and multivariate methods were
      used to analyze the effects of impairment in cognitive and decision-making
      abilities on willingness to participate in research. RESULTS: There were no
      differences in willingness to participate found between the Alzheimer's and the
      healthy comparison subjects for three of the four hypothetical protocols. In both
      groups, willingness declined as risk increased. Within the Alzheimer's disease
      group, the presence of greater decisional impairment tended to predict less
      willingness to participate in research, even after adjusting for cognitive
      impairment, gender, and education. CONCLUSIONS: Persons with decisional
      impairment due to Alzheimer's disease are as a group able to distinguish between
      research protocols of varying risk/benefit profiles. Because declining decision
      making abilities may predict declining willingness to participate in research,
      informed consent procedures for Alzheimer's disease research should be sensitive
      to this possibility.

PMID- 11986135
TI  - A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with
      schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: Some genome-wide scans and association studies for schizophrenia
      susceptibility genes have yielded significant positive findings, but there is
      disagreement between studies on their locations, and no mutation has yet been
      found in any gene. Since schizophrenia is a complex disorder, a study with
      sufficient power to detect a locus with a small or moderate gene effect is
      necessary. METHOD: In a genome-wide scan of 382 sibling pairs with a diagnosis of
      schizophrenia or schizoaffective disorder, 396 highly polymorphic markers spaced
      approximately 10 centimorgans apart throughout the genome were genotyped in all
      individuals. Multipoint nonparametric linkage analysis was performed to evaluate
      regions of the genome demonstrating increased allele sharing, as measured by a
      lod score. RESULTS: Two regions with multipoint maximum lod scores suggesting
      linkage were found. The highest lod scores occurred on chromosome 10p15-p13 (peak
      lod score of 3.60 at marker D10S189) and the centromeric region of chromosome 2
      (peak lod score of 2.99 at marker D2S139). In addition, a maximum lod score of
      2.00 was observed with marker D22S283 on chromosome 22q12, which showed evidence
      of an imprinting effect, whereby an excess sharing of maternal, but not paternal,
      alleles was present. No evidence of linkage was obtained at several locations
      identified in previous studies, including chromosomes 1q, 4p, 5p-q, 6p, 8p, 13q,
      15p, and 18p. CONCLUSIONS: The findings of this large genome-wide scan emphasize
      the weakness and fragility of linkage reports on schizophrenia. No linkage
      appears to be consistently replicable across large studies. Thus, it has to be
      questioned whether the genetic contribution to this disorder is detectable by
      these strategies and the possibility raised that it may be epigenetic, i.e.,
      related to gene expression rather than sequence variation. Nevertheless, the
      positive findings on chromosome 2, 10, and 22 should be pursued further.

PMID- 11986136
TI  - Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion
      tensor imaging study.
AB  - OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may
      explain some of the symptoms observed in schizophrenia. Conventional magnetic
      resonance imaging (MRI) studies, however, have not shown compelling evidence for
      white matter abnormalities, because white matter fiber tracts cannot be
      visualized by conventional MRI. Diffusion tensor imaging is a relatively new
      technique that can detect subtle white matter abnormalities in vivo by assessing
      the degree to which directionally organized fibers have lost their normal
      integrity. The first three diffusion tensor imaging studies in schizophrenia
      showed lower anisotropic diffusion, relative to comparison subjects, in whole
      brain white matter, prefrontal and temporal white matter, and the corpus
      callosum, respectively. Here the authors focus on fiber tracts forming temporal
      frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate
      fasciculus, the most prominent white matter tract connecting temporal and frontal
      brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison
      subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line
      scan diffusion tensor images. Maps of the fractional anisotropy were generated to
      quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings
      revealed a group-by-side interaction for fractional anisotropy and for uncinate
      fasciculus area, derived from automatic segmentation. The patients with
      schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in
      the comparison subjects. CONCLUSIONS: These findings demonstrate the importance
      of investigating white matter tracts in vivo in schizophrenia and support the
      hypothesis of a disruption in the normal pattern of connectivity between temporal
      and frontal brain regions in schizophrenia.

PMID- 11986137
TI  - Estimated neuronal populations and volumes of the hippocampus and its subfields
      in schizophrenia.
AB  - OBJECTIVE: It has been suggested that the primary focus of the pathological
      process in schizophrenia is on the limbic system, and there have been several
      postmortem reports of changes in the histological structure or volume of the
      hippocampus, as well as a larger number of MRI reports of volume reductions.
      There are conflicting findings, however, with both techniques. METHOD: The
      authors conducted a study of the gross and subfield structure and cellular
      composition of the hippocampus in postmortem brains from 30 patients with DSM-IV
      diagnosed schizophrenia (13 women, 17 men) and 29 comparison subjects with no
      psychopathology (14 women, 15 men). Stereological sampling procedures were
      applied to 25-microm-thick coronal paraffin sections taken at 5-mm intervals
      throughout the formalin-fixed hippocampus. Subfields were defined as the dentate
      fascia, the hilus (CA4), an amalgamation of the CA2 and CA3 subfields, the CA1
      subfield, and the subiculum. Volumes, cell densities, and cell numbers of the
      subfields were assessed microscopically, and the volume of the hippocampus was
      estimated from both photographs and histological slides of the coronal slices.
      RESULTS: As assessed from histologically stained slides, the volumes of the
      hippocampus and its subfields did not differ between patients and comparison
      subjects. Left-sided reduction in hippocampal volumes estimated from photographs,
      which may have included parahippocampal tissue, was not confirmed on histological
      examination. No significant differences were observed between patients and
      comparison subjects in the cellular composition of the hippocampus. CONCLUSIONS:
      These findings do not support a primary alteration of the hippocampus in
      schizophrenia.

PMID- 11986138
TI  - Supplementing clinic-based skills training with manual-based community support
      sessions: effects on social adjustment of patients with schizophrenia.
AB  - OBJECTIVE: Although skills training is a validated psychosocial treatment for
      schizophrenia, generalization of the skills to everyday life has not been
      optimal. This study evaluated a behaviorally oriented method of augmenting clinic
      based skills training in the community with the aim of improving opportunities,
      encouragement, and reinforcement for outpatients to use their skills in their
      natural environment. METHOD: Sixty-three individuals with schizophrenia were
      randomly assigned to 60 weeks of clinic-based skills training alone or of clinic
      based skills training supplemented with manual-based generalization sessions in
      the community. Patients were also randomly assigned to receive either haloperidol
      or risperidone. Therapists' fidelity to the manuals was measured. Patients'
      acquisition of the skills from pre- to posttraining was evaluated. The primary
      outcome measures were the Social Adjustment Scale-II and the Quality of Life
      Scale. RESULTS: Seventy-one percent of the patients completed the trial. Only six
      participants experienced psychotic exacerbations during the trial. There was no
      evidence of a differential medication effect on social functioning. Social
      functioning improved modestly in both psychosocial conditions over time;
      participants who received augmented skills training in the community showed
      significantly greater and/or quicker improvements. CONCLUSIONS: Given judicious
      and effective antipsychotic medication that limited exacerbations to less than
      10% during the trial, a wide range of outpatients with schizophrenia demonstrated
      substantial learning of illness management and social skills in the clinic. When
      clinic-based skills training was augmented by in vivo training and consultation,
      transfer of the skills to everyday life was enhanced. These benefits were
      established regardless of the medications prescribed.

PMID- 11986139
TI  - Test-retest stability of the Repeatable Battery for the Assessment of
      Neuropsychological Status in schizophrenia.
AB  - OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status
      (RBANS) was designed as a cognitive screening test, providing both a total scale
      score and five specific cognitive ability index scores. This study examined the
      test-retest stability of the RBANS in individual patients with schizophrenia
      relative to a healthy comparison group. METHOD: A total of 181 patients with
      schizophrenia or schizoaffective disorder were recruited from three clinical
      settings. Healthy comparison subjects were recruited as part of the RBANS
      standardization. Participants were administered one form of the RBANS on one
      occasion and another form at a later date, with intervals ranging from 1 to 134
      days. RESULTS: Intraclass correlation coefficients for the RBANS total scale were
      0.84 for the patients with schizophrenia and 0.77 for the healthy comparison
      subjects. Confidence intervals and percentile data for the total scale change
      scores were similar for both groups. CONCLUSIONS: The RBANS demonstrated
      reasonable intraclass correlation coefficient test-retest reliability for both
      schizophrenia patients and healthy comparison subjects. Confidence intervals are
      comparable to those previously published for the WAIS-R and Wechsler Memory Scale
      Revised, suggesting that retest measurement error is not dramatically increased
      in the RBANS, despite the brevity of the test. These data may serve as an
      informative guide for using the RBANS to evaluate neuropsychological change on
      the level of the individual subject.

PMID- 11986140
TI  - Dropping out of mental health treatment: patterns and predictors among
      epidemiological survey respondents in the United States and Ontario.
AB  - OBJECTIVE: The authors interviewed individuals treated for self-described mental
      health problems in the preceding year to examine patterns and predictors
      associated with dropping out of treatment. METHOD: Subjects were drawn from
      respondents to community epidemiological surveys carried out in representative
      samples of the United States and Ontario populations. Dropouts were those who had
      left mental health treatment during the prior year for reasons other than symptom
      improvement. The surveys also assessed potential dropout correlates:
      sociodemographic characteristics, attitudes about mental health care, disorder
      type, provider type, and treatment received. RESULTS: The proportion of dropouts
      did not significantly differ between the United States (19.2%) and Ontario
      (16.9%), nor did the effects of the predictors differ significantly between the
      two samples. Sociodemographic characteristics associated with treatment dropout
      included low income, young age, and, in the United States, lacking insurance
      coverage for mental health treatment. Patient attitudes associated with dropout
      included viewing mental health treatment as relatively ineffective and
      embarrassment about seeing a mental health provider. Respondents who received
      both medication and talk therapy were less likely to drop out than those who
      received single-modality treatments. CONCLUSIONS: Mental health treatment dropout
      is a serious problem, especially among patients who have low income, are young,
      lack insurance, are offered only single-modality treatments, and have negative
      attitudes about mental health care. Cost-effective interventions targeting these
      groups are needed to increase the proportion of patients who complete an adequate
      course of treatment.

PMID- 11986141
TI  - Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive
      compulsive disorder.
AB  - OBJECTIVE: The study tested the effect of comorbid posttraumatic stress disorder
      (PTSD) on behavior therapy outcome for obsessive-compulsive disorder (OCD).
      METHOD: Subjects were 15 patients with treatment-refractory OCD who were admitted
      consecutively to a short-term residential facility. Eight met DSM-IV criteria for
      comorbid PTSD. Patients participated in coached and self-directed behavior
      treatments of exposure and response prevention as well as in group treatments
      targeting specific OCD symptoms and related difficulties. Severity of OCD and
      depression were assessed at admission and exit. RESULTS: Patients with comorbid
      PTSD showed no significant improvements in OCD and depression symptoms. OCD and
      depression symptoms improved significantly more in patients without comorbid PTSD
      than in patients with comorbid PTSD. CONCLUSIONS: Behavioral treatment (with or
      without medication) of OCD may be adversely affected by the presence of comorbid
      PTSD.

PMID- 11986142
TI  - Sleep complaints as early predictors of posttraumatic stress disorder: a 1-year
      prospective study of injured survivors of motor vehicle accidents.
AB  - OBJECTIVE: Disturbed sleep is a common complaint among patients with
      posttraumatic stress disorder (PTSD) that appears in the reexperiencing and
      hyperarousal symptom clusters in DSM-IV. The causal relationship between sleep
      complaints and PTSD is unclear. METHOD: Self-reported insomnia and excessive
      daytime sleepiness were assessed in 102 victims of motor vehicle accidents and 19
      comparison subjects 1 week and 1, 3, 6, and 12 months after the trauma. At 12
      months the Structured Clinical Interview for DSM-III-R was administered to
      determine diagnoses of PTSD. RESULTS: Twenty-six of the accident victims but none
      of the comparison subjects met the criteria for PTSD. Logistic regression models
      indicated that sleep complaints from 1 month on were significant in predicting
      PTSD at 1 year. CONCLUSIONS: These results suggest that on the basis of sleep
      complaints as early as 1 month after the trauma, it is possible to detect
      subjects who will later develop chronic PTSD.

PMID- 11986143
TI  - Psychiatric disorders in rescue workers after the Oklahoma City bombing.
AB  - OBJECTIVE: Psychiatric disorders were studied in a volunteer group of 181
      firefighters who served as rescue/recovery workers after the Oklahoma City
      bombing. METHOD: Approximately 34 months after the disaster, the authors
      retrospectively assessed psychopathology both before and after the bombing with
      the Diagnostic Interview Schedule. Findings for male rescue workers were compared
      with those of male primary victims who had been in the direct path of the blast
      and who had been assessed with the same instrument. RESULTS: The prevalence of
      posttraumatic stress disorder related to the bombing was significantly lower in
      male rescue workers (13%) than in male primary victims (23%). High rates of
      alcohol disorders (postdisaster: 24%; lifetime: 47%) were seen among all rescue
      workers, with virtually no new cases occurring after the bombing. CONCLUSIONS:
      The resilience seen in firefighters may be related to their career selection,
      their preparedness and experience, the fewer injuries they suffered, and
      postdisaster mental health interventions. However, alcohol disorders were endemic
      before the disaster, indicating a need for ongoing programs targeting this
      problem.

PMID- 11986144
TI  - Mental health care quality under managed care in the United States: a view from
      the Health Employer Data and Information Set (HEDIS).
AB  - OBJECTIVE: This study examined the rates and correlates of mental health care
      performance measures in the Health Employer Data and Information Set (HEDIS).
      METHOD: For all 384 health maintenance organizations (HMOs) participating in the
      HEDIS program of the National Committee for Quality Assurance during 1999,
      analyses examined the rates of compliance with five mental health care
      performance measures and their association with general medical care quality,
      public reporting, and HMO finances. RESULTS: The mean rate of mental health care
      performance was 48.0%, compared with 69.2% for non-mental-health care domains. In
      multivariate models adjusted for plan characteristics, scores for worse quality
      of non-mental-health domains, failure to report data publicly, and low medical
      loss ratio (proportion of revenues spent on clinical care) all predicted poor
      mental health care performance. CONCLUSIONS: Better general medical care,
      transparency of reporting, and commitment of fiscal resources to clinical care
      predicted better mental health care performance for U.S. HMOs.

PMID- 11986145
TI  - Prospective diagnosis of the initial prodrome for schizophrenia based on the
      Structured Interview for Prodromal Syndromes: preliminary evidence of interrater
      reliability and predictive validity.
AB  - OBJECTIVE: This study was conducted to determine the interrater reliability and
      predictive validity of a set of diagnostic criteria for the prodrome of the first
      episode of schizophrenic psychosis when based on the Structured Interview for
      Prodromal Syndromes. METHOD: The subjects were patients referred for evaluation
      because of a suspected schizophrenia prodromal syndrome. For the reliability
      study, two to four raters independently diagnosed 18 patients on the basis of
      face-to-face or videotaped interviews. For the validity study, 6- and 12-month
      outcome data were collected for 29 patients. RESULTS: Agreement in
      differentiating prodromal from nonprodromal patients was 93%. The prodromal
      features had converted to schizophrenic psychosis for 46% of the prodromal
      patients at 6 months and for 54% at 12 months. CONCLUSIONS: In small groups of
      subjects, these diagnostic criteria for the schizophrenic prodrome and the
      Structured Interview for Prodromal Syndromes showed promising interrater
      reliability and predictive validity.

PMID- 11986146
TI  - Shape differences in the corpus callosum in first-episode schizophrenia and first
      episode psychotic affective disorder.
AB  - OBJECTIVE: The corpus callosum, the largest white matter tract in the brain, is a
      midline structure associated with the formation of the hippocampus, septum
      pellucidum, and cingulate cortex, which have been implicated in the pathogenesis
      of schizophrenia. Corpus callosum shape deformation, therefore, may reflect a
      midline neurodevelopmental abnormality. METHOD: Corpus callosum area and shape
      were analyzed in 14 first-episode psychotic patients with schizophrenia, 19 first
      episode psychotic patients with affective disorder, and 18 normal comparison
      subjects. RESULTS: No statistically significant corpus callosum area differences
      between groups were found, but there were differences in the structure's shape
      between the patients with schizophrenia and the comparison subjects. A
      correlation between width and angle of the corpus callosum was found in patients
      with affective disorder. CONCLUSIONS: Corpus callosum shape abnormalities in
      first-episode psychotic patients with schizophrenia may reflect a midline
      neurodevelopmental abnormality.

PMID- 11986147
TI  - Neurobiological measures of schizotypal personality disorder: defining an
      inhibitory endophenotype?
AB  - OBJECTIVE: Subjects with schizotypal personality disorder demonstrate deficits in
      inhibition when assessed on prepulse inhibition, P50 suppression, and antisaccade
      paradigms. This study determined if distinct subgroups of subjects with
      schizotypal personality disorder could be identified on the basis of performance
      on these measures and whether endophenotypes could be defined for future genetic
      study by using measures of inhibitory function. METHOD: Prepulse inhibition, P50
      suppression, and antisaccade paradigms were assessed in 21 subjects with
      schizotypal personality disorder. RESULTS: Seven subjects with schizotypal
      personality disorder had deficits on each paradigm; seven had no deficits on any
      paradigm. P50 and antisaccade deficits were present in five of the same subjects
      and significantly correlated. CONCLUSIONS: These results suggest that P50 and
      antisaccade performance reflects a common endophenotype and that prepulse
      inhibition identifies a separate endophenotype reflecting different
      neurobiological substrate(s) in subjects with schizotypal personality disorder.
      This pattern may generalize to schizophrenia spectrum disorder patients.

PMID- 11986148
TI  - Topiramate for obstructive sleep apnea and snoring.

PMID- 11986149
TI  - Fluoxetine for OCD after brain injury.

PMID- 11986150
TI  - Pulmonary embolism and severe depression.

PMID- 11986151
TI  - Cyproheptadine for drug-induced sweating.

PMID- 11986152
TI  - Antituberculosis agents and carbamazepine.

PMID- 11986153
TI  - Light therapy, obesity, and night-eating syndrome.

PMID- 11986154
TI  - Clozapine and venous thromboembolism.

PMID- 11986155
TI  - Posttermination boundary issues.

PMID- 11986157
TI  - The mind-body problem.

PMID- 11986158
TI  - Posttermination boundary issues.

PMID- 11986159
TI  - The mind-body problem.

PMID- 11986160
TI  - The mind-body problem.

PMID- 11986162
TI  - The mind-body problem.

PMID- 11986164
TI  - Abuse, dependence, or withdrawal associated with tramadol.

PMID- 11986165
TI  - Residual depressive symptoms in bipolar depression.

PMID- 11986180
TI  - Minimally invasive ablation techniques in breast cancer treatment.

PMID- 11986181
TI  - Intraoperative sentinel node assessment is a touchy subject.

PMID- 11986182
TI  - Retroperitoneal sarcoma: time for a national trial?

PMID- 11986183
TI  - Focused microwave phased array thermotherapy for primary breast cancer.
AB  - BACKGROUND: A pilot safety study of focused microwave phased array thermotherapy
      in the treatment of primary breast carcinomas was conducted. METHODS: Ten
      patients with breast carcinomas beneath the skin surface that ranged in maximal
      clinical size from 1 to 8 cm (mean, 4.3 cm) were treated with the breast
      compressed in the prone position. We planned to deliver a tumor thermal dose
      equivalent to 60 minutes at 43 degrees C. Breast imaging and pathology data were
      used to assess efficacy. RESULTS: For the 10 patients, the mean tumor equivalent
      thermal dose was 51.7 minutes, the mean peak tumor temperature was 44.9 degrees
      C, and the mean treatment time was 34.7 minutes. Ultrasound imaging demonstrated
      a significant reduction in tumor size (mean, 41%) 5 to 18 days after
      thermotherapy in 6 (60%) of 10 patients. A significant tumor response on the
      basis of reduction in tumor size or significant tumor cell kill occurred in 8
      (80%) of 10 patients. CONCLUSIONS: With sufficient skin cooling, delivery of
      focused microwave phased array thermotherapy is safe in treating breast
      carcinomas when used alone, and some potential efficacy was demonstrated at the
      tumor thermal doses administered. Increased tumor thermal dose efficacy studies
      in larger patient populations for improved breast conservation should be
      investigated.

PMID- 11986184
TI  - Intraoperative touch preparation for sentinel lymph node biopsy: a 4-year
      experience.
AB  - BACKGROUND: The optimal technique for intraoperative pathologic examination of
      sentinel lymph nodes (SLNs) is still controversial. Recent small series report
      sensitivity between 60% and 100% for various techniques. The aim of this study
      was to evaluate our long-term experience with touch preparation cytology (TPC)
      and frozen section (FS) in the intraoperative examination of SLNs for breast
      cancer. METHODS: A total of 247 patients with operable breast cancer underwent an
      SLN biopsy for staging of the axilla. The SLN was identified by (99m)Tc-labeled
      sulfur colloid unfiltered dye, blue dye, or both and dissected, and then
      intraoperative TPC or FS and permanent section, or both, were performed. RESULTS:
      A total of 479 SLNs were submitted for TPC and permanent hematoxylin and eosin. A
      total of 68 SLNs were positive by hematoxylin and eosin; 65 SLNs were positive by
      TPC, with a false-negative rate of 5.8%. The sensitivity for TPC was 94.2%, with
      a false-positive rate of 0.2%. A total of 165 SLNs were submitted for FS, with a
      sensitivity of 85.7% and a specificity of 98.6%. The false-positive rate was
      1.4%, with a false-negative rate of 15.8%. CONCLUSIONS: In a large series, TPC is
      as accurate as FS but is simpler and faster in the detection of intraoperative
      metastasis in SLNs for breast cancer.

PMID- 11986185
TI  - Prognoses of T4 breast cancer subsets.
AB  - BACKGROUND: The relative prognoses of subsets of patients with T4 breast tumors,
      since the advent of neoadjuvant therapy, are unknown, although inflammatory
      carcinoma (T4d) is considered to have the worst prognosis. METHODS: Subsets of T4
      patients were analyzed for the incidence of distant metastases at presentation
      (M1; n = 263). T4M0 patients treated with neoadjuvant therapy (n = 126) were
      analyzed for relapse-free survival (RFS). T4d tumors with (Cut/CW+) and without
      (Cut/CW-) skin nodules, posterior fixation, or both were analyzed separately.
      RESULTS: Fewer patients with T4d (Cut/CW-) tumors had distant metastases at
      presentation than T4d (Cut/CW+) patients or T4b and T4c patients (P =.001,.001,
      and.009, respectively). RFS was longer for T4b patients than for T4c patients (P
      =.018) or T4d (Cut/CW+) patients (P =.003). RFS of the T4d (Cut/CW+) patients was
      shorter than for T4d (Cut/CW-) patients (P =.050). CONCLUSIONS: The incidence of
      distant metastases at presentation was lowest, and RFS was longest, for patients
      with T4d tumors not grossly involving the skin or posterior structures. Patients
      whose tumors grossly invaded both skin and posterior structures (T4c) or those
      with T4d tumors grossly invading either most frequently presented with distant
      metastases and had the shortest RFS.

PMID- 11986186
TI  - Initial results of a trial of preoperative external-beam radiation therapy and
      postoperative brachytherapy for retroperitoneal sarcoma.
AB  - BACKGROUND: Surgical resection alone does not cure the majority of patients with
      retroperitoneal sarcoma (RPS). We evaluated the effects of preoperative external
      beam radiotherapy (XRT) and postoperative brachytherapy (BT) combined with
      complete surgical resection. METHODS: Fifty-five patients with primary or locally
      recurrent RPS judged to be resectable were entered onto a trial of combined
      therapy and observed prospectively. Forty-six patients underwent complete gross
      resection with curative intent. Of these, 41 patients completed preoperative XRT
      and 23 patients received BT. Outcome measures were treatment toxicity, overall
      survival, and disease-free survival (DFS). RESULTS: Preoperative XRT was very
      well tolerated and was associated with Radiation Therapy Oncology Group acute
      toxicity scores of < or = 2 in all patients. Acute postoperative and BT-related
      toxicity resulted in modified RTOG scores of > or = 3 in 39.1% (18 of 46) of
      patients. Late toxicity was associated with death in 4.3% (2 of 46) and with life
      threatening illness in 2.2% (1 of 46) of patients, all of whom had been treated
      with BT to the upper abdomen. The 2-year overall survival and DFS for resected
      RPS were 88% and 80%, respectively. Significantly better 2-year DFS was achieved
      in patients with primary RPS and in those with low-grade tumors (93% and 95%,
      respectively). CONCLUSIONS: The initial results of combined therapy are
      promising. Although preoperative XRT was very well tolerated, BT to the upper
      abdomen was associated with substantial toxicity. Our current protocol includes
      selective application of BT to the lower abdomen only.

PMID- 11986187
TI  - Value of continuous leakage monitoring with radioactive iodine-131-labeled human
      serum albumin during hyperthermic isolated limb perfusion with tumor necrosis
      factor-alpha and melphalan.
AB  - BACKGROUND: The aim of this study was to analyze the value of continuous leakage
      monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in
      patients treated with hyperthermic isolated limb perfusion with tumor necrosis
      factor-alpha (TNF alpha) and melphalan. METHODS: Forty-eight patients with
      melanoma (n = 14) or soft tissue sarcoma (n = 34) of an extremity underwent 51
      perfusions. Perfusion was performed at the iliac level in 22 cases, at the
      popliteal level in 16 cases, at the femoral level in 7 cases, and at the axillary
      level in 6 cases. Leakage rates and perfusion circuit and systemic levels of TNF
      alpha, interleukin-6, and C-reactive protein were determined, as were systemic
      hematological and metabolic profiles and tumor response. RESULTS: The mean
      isotopically measured leakage was 2.9%. Systemic leakage was < or = 2% in 28
      perfusions and >2% in 23 perfusions. The correlation between the maximal
      monitored leakage and maximal systemic TNF alpha levels was.7114. The area under
      the curve for TNF alpha in the perfusion circuit, indicating the exposure of the
      perfused limb to TNF alpha, was 18.7% lower in the >2% leakage group. No
      significant differences in tumor response were found between groups. The area
      under the curve for systemic TNF alpha, indicating the exposure of the patient to
      TNF alpha, was 18.1 times higher in the >2% leakage group, resulting in a
      significant decrease in leukocyte and platelet count, hyperbilirubinemia,
      hypocholesterolemia, and proteinemia. No beneficial effect of the systemically
      leaked TNF and melphalan was seen on the occurrence of distant metastasis during
      follow-up. There was a significant difference between perfusions performed at the
      iliac and femoral levels compared with leakage values at the popliteal level.
      CONCLUSIONS: A good correlation between RISA leakage measurement and TNF alpha
      exposure during and after hyperthermic isolated limb perfusion with TNF alpha and
      melphalan was demonstrated. RISA leakage measurement serves as a good guide for
      the effectiveness of isolation during perfusion. If leakage exceeds the 2% limit
      during perfusion, less exposure of the tumor-bearing limb to TNF alpha, increased
      exposure of the patient systemic circulation to TNF alpha, and more systemic side
      effects can be expected.

PMID- 11986188
TI  - Intraoperative molecular detection of circulating tumor cells by reverse
      transcription-polymerase chain reaction in patients with biliary-pancreatic
      cancer is associated with hematogenous metastasis.
AB  - BACKGROUND: Circulating tumor cells in the blood were frequently detected by
      reverse transcription-polymerase chain reaction during operation in patients with
      biliary-pancreatic cancer. We investigated the relationship between circulating
      tumor cells during operation and hematogenous metastases. METHODS: Blood samples
      from 67 patients with biliary-pancreatic cancer were obtained from the portal
      vein, peripheral artery, and superior vena cava during operation. After total RNA
      was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific
      reverse transcription-polymerase chain reaction was performed. RESULTS:
      Intraoperative CEA-messenger RNA (mRNA) expression was detected in the blood of
      32 (47.8%) of 67 patients with biliary-pancreatic cancer, although it was not
      detected in the blood obtained from 20 healthy volunteers or 15 patients with
      benign disease of the biliary pancreas. The incidence (37.5%) of hematogenous
      metastases after surgery in the CEA-mRNA-positive group (n = 32) was
      significantly higher than that (11.4%) in the negative group (n = 35; P =.01). In
      stage I, II, and III patients, survival of the CEA-mRNA-positive group was
      significantly worse compared with that of negative group (P =.03). CONCLUSIONS:
      Intraoperative molecular detection of circulating tumor cells in patients with
      biliary-pancreatic cancer relates to a high risk of hematogenous metastasis and
      is associated with unfavorable prognosis even after curative resection.

PMID- 11986189
TI  - Deficient expression of O(6)-methylguanine-DNA methyltransferase combined with
      mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human
      biliary tract carcinoma.
AB  - BACKGROUND: O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair
      enzyme that transfers methyl groups from O(6)-methylguanine to itself. Alkylation
      of DNA at the O(6) position of guanine is an important step in the induction of
      mutations in the organism by alkylating agents. The O(6)-methyl G:T mismatch is
      recognized by the mismatch-repair (MMR) pathway. The biliary duct is highly
      exposed to alkylating agents because of its anatomical location. METHODS: We
      examined 39 surgically resected gallbladder carcinomas and 35 extrahepatic bile
      duct carcinomas and evaluated the expression of MGMT and MMR protein (hMLH1 and
      hMSH2) by immunohistochemical staining. RESULTS: MGMT-negative staining was
      detected in 59.0% of gallbladder carcinoma specimens and 60.0% of extrahepatic
      bile duct carcinoma specimens. In gallbladder carcinoma, hMLH1- and hMSH2
      negative staining was observed in 51.3% and 59.0%, respectively, whereas in
      extrahepatic bile duct carcinoma, the respective values were 57.1% and 65.7%.
      MGMT-negative staining correlated with hepatic invasion in gallbladder carcinoma
      and with poor prognosis in both types of tumor. Furthermore, a combined MGMT and
      MMR status was shown to be a more significant prognostic biomarker in both tumor
      types. CONCLUSIONS: Combined MGMT and MMR is a possible prognostic marker that
      probably reflects an accumulation of genetic mutations.

PMID- 11986190
TI  - A population-based study of the extent of surgical resection of potentially
      curable colon cancer.
AB  - BACKGROUND: We attempted to determine factors contributing to the extent of
      initial curative resection for colon cancer in a population-based cohort. Total
      abdominal colectomy with ileorectal anastomosis (TAC-IR) may be considered for
      young patients or those with a colorectal cancer family history to prevent
      metachronous lesions and facilitate surveillance. METHODS: All Ontario patients
      newly diagnosed with colon cancer over 12 months beginning in July 1997 were
      staged at the time of surgery. The extent of resection was compared with
      variables, including familial risk obtained from the Ontario Familial Colon
      Cancer Registry. RESULTS: Complete staging was possible for 86% of patients. A
      total of 1223 patients had a potentially curative resection: 17%, 46%, and 36%
      were stage I, II, and III, respectively. Patients were more likely to receive a
      TAC-IR if they were < or = 50 years old (odds ratio [OR], 3.5; 95% confidence
      interval [CI], 1.8-6.6), if they had a synchronous lesion (OR, 28.37; 95% CI,
      12.2-61.2), or if they were at a teaching hospital (OR, 2.8; 95% CI, 1.6-4.7),
      but not if they had a family history (OR,.7; 95% CI,.3- 1.5). CONCLUSIONS: Young
      age, teaching hospital, and multiple cancers but not family history were
      important factors for performing a TAC-IR.

PMID- 11986191
TI  - RCAS1 expression as a prognostic factor after curative surgery for extrahepatic
      bile duct carcinoma.
AB  - BACKGROUND: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a
      cancer cell-surface antigen and has been identified as a prognostic factor in
      several cancers. It is thought that tumor cells escape from immune attack by
      expressing RCAS1, which induces apoptosis in receptor-positive immune cells. We
      investigated the relationship between RCAS1 expression and clinicopathologic
      features and clinical outcome in patients with extrahepatic bile duct carcinoma
      (EBDC) who underwent curative resection. METHODS: RCAS1 expression was determined
      by immunohistochemistry in 60 patients with EBDC who underwent curative resection
      from 1992 to 1999. The patients were divided into two groups on the basis of the
      extent of RCAS1 expression: a low-expression group (immunoreactivity in <25% of
      cells) and a high-expression group. Expression was correlated with
      clinicopathologic features and prognosis. RESULTS: RCAS1 was expressed in 52
      (86.7%) of 60 tumors and at a high frequency in all histopathologic stages. High
      expression of RCAS1 was detected in 46 (76.7%) of 60 cases. No correlation
      existed between the pattern of RCAS1 expression and any clinicopathologic
      feature, although high expression did correlate with poor prognosis. High RCAS1
      expression was an independent negative predictor for survival. CONCLUSIONS: RCAS1
      expression predicts poor outcome in resectable EBDC.

PMID- 11986192
TI  - Recurrence patterns after radical gastrectomy for gastric cancer: prognostic
      factors and implications for postoperative adjuvant therapy.
AB  - BACKGROUND: A recent Intergroup trial demonstrated a significant survival
      advantage of postgastrectomy chemoradiation in gastric cancer patients, primarily
      because of a reduction of a relative locoregional recurrence (LRR) rate exceeding
      70% in control patients. Radical gastrectomy with extended lymphadenectomy may
      reduce LRR, possibly affecting adjuvant treatment strategies. METHODS:
      Information on patients undergoing gastrectomy for potentially curable gastric
      cancer between 1990 and 2000 was reviewed. Patterns of first disease recurrence,
      survival, and disease-free survival were calculated, and predictors were
      identified. RESULTS: Gastrectomies were performed in 73 patients, with R0
      resections in 82%. The median lymph node count was 24; positive nodes were found
      in 64% of patients. The median actuarial survival was 27 months, with a 5-year
      survival of 37%. Disease recurred in 35 patients (48%) after a median interval of
      7 months (range,.5-67). Recurrent disease patterns included distant only (37%),
      peritoneal only (23%), peritoneal/locoregional (17%), all sites combined (14%),
      locoregional only (6%), and distant/locoregional (3%). Recurrence predictors were
      N3 category for distant recurrence (hazard ratio [HR], 10.2; P =.005), T3/4
      category for peritoneal recurrence (HR, 4.8; P =.008), peritoneal relapse (HR,
      40; P =.002), and a prior abdominal operation for LRR (HR, 3.2; P =.01). N2
      disease had a distant failure risk similar to N1 status and an intraperitoneal
      failure risk similar to an N3 category. CONCLUSIONS: Isolated LRR of gastric
      cancer after gastrectomy and extended lymphadenectomy is rare in this series.
      Most recurrences appeared diffusely at distant or peritoneal sites, and most LRRs
      occurred in conjunction with relapse at extraregional sites. Pathologic
      predictors of intraperitoneal (T3/4) or systemic failure (>N1) could be used to
      guide individualized, risk-oriented, adjuvant treatment.

PMID- 11986193
TI  - Is D2 lymph node dissection necessary for early gastric cancer?
AB  - BACKGROUND: The objective of this study was to clarify a survival benefit of D2
      lymphadenectomy in patients with early gastric carcinoma (GC). METHODS: A
      retrospective study was conducted to examine the incidence of metastasis to level
      2 lymph nodes, the causes of postoperative death, and the mode of recurrence in
      1041 patients who had early GC and underwent D2 lymphadenectomy with curative
      intent. RESULTS: Postoperative mortality occurred in 129 (12.4%) of 1041
      patients, 6 patients (.6%) died of surgical complications, 108 (10.2%) died of
      diseases other than cancer, and 16 (1.5%) died of recurrence. Hematogenous
      metastasis was the major mode of recurrence (56.3% of recurrences). The incidence
      of metastasis to level 2 nodes was 2.5% (26 of 1041 patients, 18 of whom were
      alive). Thus, the estimated survival benefit of radical lymphadenectomy for
      patients with early GC was calculated to be 1.7% (18 of 1041 patients).
      CONCLUSIONS: D2 lymphadenectomy in patients with early GC had little survival
      benefit because (1) metastasis to level 2 nodes was rare, (2) most causes of
      death were not related to the tumor, and (3) more than half the recurrences were
      hematogenous. Use of radical lymphadenectomy for early GC should be limited.

PMID- 11986194
TI  - The First International Conference on Sentinel Node Biopsy in Mucosal Head and
      Neck Cancer and adoption of a multicenter trial protocol.
AB  - BACKGROUND: Sentinel node biopsy (SNB) is a new technique in staging the
      clinically N0 neck. On June 25 and 26, 2001, the First International Conference
      on Sentinel Node Biopsy in Mucosal Head and Neck Cancer took place in Glasgow,
      United Kingdom. METHODS: Twenty-two centers contributed results on the use of SNB
      as a staging tool in head and neck squamous cell carcinoma. The pathology of the
      sentinel node was compared with that of the pathologic neck specimen. RESULTS:
      Three hundred sixteen clinically N0 necks were included. Sentinel nodes were
      identified in 301 necks (95%). Of these 301 necks, 76 necks were staged positive
      with SNB, and 225 were staged negative. The overall sensitivity of the procedure
      was 90%. Centers who had performed < or = 10 cases had a lower sensitivity (57%),
      discovering only 4 of 7 metastatic nodes, in comparison with 72 of 77 metastatic
      nodes discovered for centers that had performed >10 cases (sensitivity, 94%).
      CONCLUSIONS: The cumulative results of all those who contributed to the first
      international conference confirm that there is a role for SNB for staging the
      clinically N0 neck, and it has a similar sensitivity to that of a staging neck
      dissection.

PMID- 11986195
TI  - Mature CD83(+) dendritic cells infected with recombinant gp100 vaccinia virus
      stimulate potent antimelanoma T cells.
AB  - BACKGROUND: Mature dendritic cells (DCs) are potent antigen-presenting cells that
      activate naive T lymphocytes and initiate cellular immune responses. The ability
      of CD83(+) mature DCs infected with vaccinia virus encoding the gp100 melanoma
      transgene (rV-gp100) to stimulate an antimelanoma CD8(+) T-cell response was
      investigated. METHODS: Monocyte-derived immature or CD83(+) mature DCs were
      infected with rV-gp100. The activation state of the DCs and the expression of
      gp100 protein were evaluated by flow cytometry. The reactivity of antimelanoma
      CD8(+) T cells was confirmed by measuring specific interferon gamma secretion by
      using enzyme-linked immunosorbent assay in a mixed-tumor lymphocyte culture.
      RESULTS: Both immature and CD83(+) mature DCs expressed gp100 protein when the
      DCs were infected with rV-gp100. Calcium-signaling agents were required to induce
      maturation of both infected and noninfected immature DCs. Only rV-gp100-infected
      CD83(+) DCs induced CD8(+) T cells, after a single stimulation that recognized
      both peptide-pulsed target cells to multiple gp100 epitopes and a melanoma cell
      line that endogenously expressed gp100 antigen. CONCLUSIONS: CD83(+) DCs
      transduced with rV-gp100 are capable of generating a strong CD8(+) T-cell
      response against melanoma tumor cells. Expression of melanoma antigens by mature
      DCs offers the potential advantage of presenting multiple endogenously processed
      T-cell epitopes and using multiple HLA restriction elements for antimelanoma
      vaccine therapy.

PMID- 11986199
TI  - The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory
      cells inhibits graft-versus-host disease lethality.
AB  - Immune regulatory CD4(+)CD25(+) cells play a vital role in the induction and
      maintenance of self-tolerance and the prevention of autoimmunity. Recently,
      CD4(+)CD25(+) cells have been shown to be required for the ex vivo induction of
      tolerance to alloantigen via costimulatory blockade and to inhibit allogeneic
      skin graft rejection. Data presented here demonstrate that CD4(+)CD25(+) cells
      play an important role in graft-versus-host disease (GVHD) generation. Depletion
      of CD4(+)CD25(+) cells from the donor T-cell inoculum or in vivo CD25-depletion
      of the recipient before transplantation resulted in increased GVHD mediated by
      CD4(+) or whole T cells in several strain combinations irrespective of the total
      body irradiation conditioning regime. The infusion of freshly purified donor
      CD4(+)CD25(+) cells modestly inhibited GVHD when administered in equal numbers
      with whole CD4(+) cells. Because CD4(+)CD25(+) cells only account for 5% to 10%
      of the total CD4(+) population, the administration of high numbers of fresh donor
      CD4(+)CD25(+) cells may not be clinically practical. However, we found that large
      numbers of CD4(+)CD25(+) cells can be obtained by ex vivo activation and
      expansion. Cultured CD4(+)CD25(+) cells, administered in equal numbers with
      CD4(+) T cells or CD25-depleted whole T cells, resulted in significant inhibition
      of rapidly lethal GVHD. To our knowledge, this study is the first to demonstrate
      that activated, cultured CD4(+)CD25(+) cells can offer substantial protection in
      a relevant in vivo animal model of disease. These data have important
      ramifications for clinical bone marrow and solid organ transplantation.
      CD4(+)CD25(+) cells warrant consideration as an exciting new modality of cellular
      therapy for the inhibition of undesirable autologous and allogeneic responses.

PMID- 11986200
TI  - Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD)
      mice.
AB  - The glycoprotein CD47 (integrin-associated protein, IAP) is present on the
      surface of virtually all cells, including red blood cells (RBCs). CD47 acts like
      a marker of self by ligating the macrophage inhibitory receptor signal regulatory
      protein alpha (SIRPalpha). In this manner mild reactivity of wild-type RBCs with
      macrophage phagocytic receptors is tolerated, whereas otherwise identical CD47
      deficient RBCs are rapidly eliminated. We show here that virtually all CD47
      deficient nonobese diabetic (NOD) mice spontaneously develop severe lethal
      autoimmune hemolytic anemia (AIHA) at 180 to 280 days of age, whereas none of the
      control CD47(+) NOD mice develop lethal AIHA at least during the first year of
      life. This phenotype is at least partially due to a markedly increased rate of
      elimination of opsonized CD47(-/-) compared to CD47(+) RBCs. Similarly, CD47(-/
      )C57BL/6 mice were much more sensitive than their wild-type counterparts to
      experimental passive AIHA induced by anti-RBC monoclonal antibodies. Thus, CD47
      SIRPalpha signaling can have a profound influence on the severity of AIHA, making
      manipulation of this signaling pathway a theoretically appealing avenue in the
      treatment of the disease.

PMID- 11986201
TI  - Regulation of ferritin genes and protein.

PMID- 11986202
TI  - A white blood cell index as the main prognostic factor in t(8;21) acute myeloid
      leukemia (AML): a survey of 161 cases from the French AML Intergroup.
AB  - While the t(8;21) translocation is one of the most recurrent chromosomal
      abnormalities in acute myeloid leukemia, prognostic studies have been hampered by
      the relatively few number of patients reported. We thus performed a large
      retrospective study in 161 adults and children with t(8;21) acute myeloid
      leukemia, all prospectively enrolled in 6 different trials conducted in France
      between 1987 and 1998 (median follow-up 4.9 years). Prognostic studies were
      performed in the 154 patients who achieved a complete remission. Individual data
      were registered, including sex, age, blood and marrow counts, extramedullary
      disease, and cytogenetics. The value of allogeneic stem cell transplantation
      versus chemotherapy as postremission therapy was evaluated according to the
      intent-to-treat principle. Estimated 5-year disease-free survival (DFS) and
      overall survival were 52% and 59%, respectively. Outcome was not significantly
      better in patients from the stem cell transplantation group (estimated 5-year DFS
      and survival, 56% vs 52% and 67% vs 57%; P =.55 and.64, respectively). White
      blood cell count (WBC) was the only identified prognostic factor. To further take
      into account the spontaneous differentiation potential of the leukemic clone, a
      WBC index was derived as the product of WBC by the ratio of marrow blast. This
      WBC index was a more powerful factor than the original WBC, allowing us to
      distinguish 3 subgroups of patients with different outcomes (low index, < 2.5;
      intermediate index, 2.5-20; high index, 20 or more). In multivariate analysis,
      the WBC index was the only prognostic factor for DFS (P =.003), complete
      remission duration (P =.002), and overall survival (P =.04).

PMID- 11986203
TI  - Mannose-binding lectin gene polymorphisms are associated with major infection
      following allogeneic hemopoietic stem cell transplantation.
AB  - Life-threatening complications such as graft versus host disease and infection
      remain major barriers to the success of allogeneic hemopoietic stem cell
      transplantation (SCT). While pretransplantation conditioning and
      posttransplantation immunosuppression are important risk factors for infection,
      the reasons that similarly immunosuppressed transplant recipients show marked
      variation in frequency of infection after allogeneic SCT are unclear. Mannose
      binding lectin (MBL) deficiency is a risk factor for infection in other
      situations where immunity is compromised. We investigated associations between
      MBL2 gene polymorphisms and risk of major infection following allogeneic SCT.
      Ninety-seven related allogeneic donor-recipient pairs were studied. Clinical data
      including survival, days of fever, graft versus host disease incidence and
      severity, and infection were collected by case note review. Five single
      nucleotide polymorphisms in the MBL2 gene were genotyped using the polymerase
      chain reaction and sequence-specific primers. MBL2 coding mutations were
      associated with an increased risk of major infection following transplantation.
      This association was seen for donor (P =.002, odds ratio [OR] 4.1) and recipient
      (P =.04, OR 2.6) MBL2 genotype. MBL2 promoter variants were also associated with
      major infection. The high-producing haplotype HYA was associated with a markedly
      reduced risk of infection (recipient HYA P =.0001, OR 0.16; donor HYA P =.001, OR
      0.23). Donor MBL2 coding mutations and recipient HYA haplotype were independently
      associated with infection in multivariate analysis. These results suggest that
      MBL2 genotype influences the risk of infection following allogeneic SCT and that
      both donor and recipient MBL2 genotype are important. These findings raise the
      possibility that MBL replacement therapy may be useful following transplantation.

PMID- 11986204
TI  - Imatinib induces hematologic and cytogenetic responses in patients with chronic
      myelogenous leukemia in myeloid blast crisis: results of a phase II study.
AB  - Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and
      is highly refractory to therapy. CML is caused by expression of the chimeric BCR
      ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia
      translocation. Imatinib (Glivec, formerly STI571) is a rationally developed,
      orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260
      patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed
      diagnosis of CML in blast crisis. Patients were treated with imatinib in daily
      oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of
      patients and sustained hematologic responses lasting at least 4 weeks in 31% of
      patients, including complete hematologic responses in 8%. For patients with a
      sustained response, the estimated median response duration was 10 months.
      Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the
      responses being complete. Median survival time was 6.9 months. Nonhematologic
      adverse reactions were frequent but generally mild or moderate. Episodes of
      severe cytopenia were also frequent and were attributable to the underlying
      condition and treatment with imatinib. Drug-related adverse events led to
      discontinuation of therapy in 5% of patients, most often because of cytopenia,
      skin disorders, or gastrointestinal reactions. These results demonstrate that
      imatinib has substantial activity and a favorable safety profile when used as a
      single agent in patients with CML in blast crisis. Additional clinical studies
      are warranted to explore the efficacy and feasibility of imatinib used in
      combination with other antileukemic drugs.

PMID- 11986205
TI  - Evidence that thrombocytopenia observed in humans treated with orally
      bioavailable glycoprotein IIb/IIIa antagonists is immune mediated.
AB  - Glycoprotein (GP) IIb/IIIa antagonists are effective therapeutic agents, but
      elicit thrombocytopenia with a frequency that approaches 2%. Here, we provide
      evidence that thrombocytopenia in humans treated with the GP IIb/IIIa antagonist
      roxifiban is immune mediated. Two patients underwent conversion to a highly
      positive drug-dependent antibody (DDAB) status temporally associated with
      thrombocytopenia. Despite the continued presence of DDABs, the fall in platelet
      count was reversed by discontinuation of drug treatment, pointing to the
      exquisite drug dependency of the immune response. DDABs appear to bind to
      neoepitopes in GP IIb/IIIa elicited on antagonist binding. This information was
      used to develop an enzyme-linked immunosorbent assay (ELISA) for DDAB using solid
      phase GP IIb/IIIa. A high level of specificity is indicated by the observation
      that DDAB binding is dependent on the chemical structure of the GP IIb/IIIa
      antagonist and that only 2% to 5% of human blood donors and 5% of chimpanzees
      present with pre-existing DDABs. Furthermore, none of 108 nonthrombocytopenic
      patients from the phase II roxifiban study showed an increase in antibody titer.
      Absorption of thrombocytopenia plasma with platelets reduced the DDAB ELISA
      signal, indicating that the test detects physiologically relevant antibodies.
      Screening patients for pre-existing or increasing DDAB titer during treatment
      with GP IIb/IIIa antagonists may reduce the incidence of drug-induced
      thrombocytopenia.

PMID- 11986206
TI  - Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic
      myelogenous leukemia in blast phase.
AB  - Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated
      with the development and progression of Philadelphia chromosome-positive (Ph(+))
      chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr
      Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity
      in phase I and II studies of CML. Here, we describe the use of imatinib mesylate
      to treat 75 patients in blast-phase CML (median age, 53 years; 65 with
      nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a
      historical control group treated with standard cytarabine-based therapy. Imatinib
      mesylate was given as oral doses at 300 to 1000 mg per day and was the first
      salvage therapy for 47 patients. The objective response rate was 52% (39 of 75
      patients: 16 had complete and 3 had partial hematologic response; 12 had
      hematologic improvement; 7 returned to second chronic phase; and 1 had a complete
      response in extramedullary blastic disease). Response rates were not different
      between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16%
      (12 patients: 5 complete, 3 partial [Ph(+) below 35%], and 4 minor [Ph(+), 34% to
      90%]). The estimated median overall survival was 6.5 months; the estimated 1-year
      survival was 22%. Response to therapy (landmark analysis at 8 weeks) was
      associated with survival prolongation. Compared with standard cytarabine
      combinations, imatinib mesylate therapy was less toxic and produced a higher
      response rate (55% versus 29%, P =.001), longer median survival (7 versus 4
      months, P =.04), and lower 4-week induction mortality (4% versus 15%, P =.07).
      Imatinib mesylate is currently being tested in combination with other drugs to
      improve the prognosis for blast-phase CML.

PMID- 11986207
TI  - Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed
      fludarabine: results of a large international study.
AB  - This study investigated the efficacy, safety, and clinical benefit of alemtuzumab
      (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic
      leukemia exposed to alkylating agents and having failed fludarabine therapy.
      Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim
      to obtain an overall response rate of at least 20%. Dosage was increased
      gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection
      prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2
      months after treatment. Responses were assessed at weeks 4, 8, and 12, and
      patients were followed for 34 months. Overall objective response in the intent-to
      treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was
      1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months
      overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were
      alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months
      for responders. Nineteen responders survived more than 21 months. Clinical
      benefit was observed both in responders and in patients with stable disease. The
      most common adverse events were related to infusion, generally grade 1 or 2 in
      severity, occurring mainly in the first week. Grade 3 or 4 infections were
      reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who
      responded to alemtuzumab treatment developed grade 3 or 4 infections on the
      study. Alemtuzumab induced significant responses in these patients with clinical
      benefit in the majority and with acceptable toxicity in a high-risk group.

PMID- 11986208
TI  - Paraneoplastic erythrocytosis associated with an inactivating point mutation of
      the von Hippel-Lindau gene in a renal cell carcinoma.
AB  - The von Hippel-Lindau (VHL) tumor suppressor gene targets hypoxia-inducible
      transcription factors (HIFs) for proteasomal degradation. Erythrocytosis due to
      inappropriate production of erythropoietin (EPO), one of the HIF target genes, is
      a classic albeit rare finding in patients with renal cancer. We report the
      clinical to molecular analysis in a patient in whom a thrombotic myocardial
      infarction was the first manifestation of a clear cell renal carcinoma associated
      with an elevated serum EPO level (109 U/L) and erythrocytosis (hemoglobin 200 g/L
      [20 g/dL]). The tumor strongly expressed EPO messenger RNA and the 2 regulatory
      subunits HIF-1alpha and HIF-2alpha. Sequence analysis of tumor tissue identified
      a point mutation of the VHL gene (nucleotide 701 T > C) with a predicted amino
      acid exchange (Leu163Pro). This structural change, although located at distance
      to the HIF-binding region, was found to inhibit binding of HIF-1alpha to VHL,
      thus leading to accumulation of HIF, which drives EPO production.

PMID- 11986209
TI  - In vivo depletion of hematopoietic stem cells in the rat by an anti-CD45 (RT7)
      antibody.
AB  - Anti-CD45 monoclonal antibodies (mAbs) are potentially powerful tools for the
      depletion of mature leukocytes. As their application for immunotherapy also
      depends on their effects on bone marrow (BM) progeny, the in vivo effects of an
      anti-CD45 mAb (anti-RT7(a) mAb) on BM precursor cells were analyzed in a rat
      model. Anti-RT7(a) mAb treatment was performed in LEW.1W (RT1(u) RT7(a)) rats
      with the use of different dosages. In addition, major histocompatibility complex
      (MHC)-congenic BM transplantation making use of a diallelic polymorphism
      (RT7(a)/RT7(b)) of rat CD45 was applied. Following injection of anti-RT7(a) mAb
      into normal LEW.1W rats, T cells were profoundly depleted in blood, lymph nodes,
      and spleen, whereas B cells were coated only by the antibody. Single injection of
      anti-RT7(a) mAb in a high dose induced a lethal aplastic syndrome with severe
      thrombocytopenia. Rescue of antibody-treated animals with BM from congenic LEW.1W
      7B rats (RT1(u) RT7(b)) and transplantation of BM from LEW.1W rats pretreated
      with anti-RT7(a) mAb into sublethally irradiated LEW.1W-7B recipients revealed a
      profound effect of the mAb on progeny of myeloid and T-cell lineage. Following
      repeated antibody treatment of stable mixed chimeras (RT7(b)/RT7(a)), very few
      RT7(a)-positive B cells were still detectable after 6 months and their number
      declined during the subsequent year. These observations show that this anti
      RT7(a) mAb effectively depletes mature T cells as well as BM precursor cells of
      myeloid, T-cell, and thrombocytic lineage after in vivo application. In contrast,
      mature B cells are not depleted, but precursors also appear to be eliminated.
      Overall, the findings suggest that the anti-RT7(a) mAb efficiently depletes early
      rat hematopoietic stem cells.

PMID- 11986210
TI  - Lineage-specific growth factors can compensate for stem and progenitor cell
      deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G
      CSF receptor-deficient mice.
AB  - Multiple lines of evidence indicate that thrombopoietin (TPO) substantially
      impacts the number of hematopoietic stem cells and progenitors of all myeloid
      lineages. Nevertheless, tpo knock-out mice (T(-)) display thrombocytopenia only;
      blood erythroid and neutrophil levels are normal despite 60% to 85% reductions in
      stem and progenitor cells. The compensatory mechanism(s) for these deficiencies
      remains uncertain; lineage-specific cytokines such as erythropoietin or
      granulocyte colony-stimulating factor (G-CSF) have been postulated but never
      proven to be responsible. To directly test whether G-CSF can compensate for the
      myeloid progenitor cell reduction in the T(-) model of hematopoietic deficiency,
      T(-) and G-CSF-receptor knock-out (GR(-)) mice were crossed, and F1 animals bred
      to obtain doubly nullizygous mice (T(-)GR(-)). This experiment also allowed us to
      test the hypothesis that G-CSF contributes to the residual platelet production in
      T(-) mice. We found that T(-)GR(-) F2 mice displayed similar blood platelet
      levels as that seen in T(-) mice, indicating that G-CSF does not account for the
      residual megakaryopoiesis in T(-) mice. However, we also noted excessive
      perinatal mortality of T(-)GR(-) animals, caused by infection due to a profound
      and significant decrease in marrow and peripheral blood neutrophils, far greater
      than that seen in either T(-) or GR(-) mice. These data indicate that in the
      additional absence of GR, T(-) mice cannot compensate for their 62% reduction in
      myeloid progenitors and become profoundly neutropenic, supporting the hypothesis
      that G-CSF can compensate for the myeloid effects of TPO deficiency by expanding
      the pool of cells between the granulocyte-macrophage colony-forming unit and
      mature neutrophil stages of granulopoiesis.

PMID- 11986211
TI  - Fibronectin- and protein kinase C-mediated activation of ERK/MAPK are essential
      for proplateletlike formation.
AB  - The megakaryoblastic CHRF-288 cell line was used to investigate signal
      transduction pathways responsible for proplateletlike formation (PPF). The role
      of fibronectin (FN) and protein kinase C (PKC) activation in PPF were examined.
      In the presence of serum and phorbol 12-myristate 13-acetate (PMA), a PKC
      activator, cells exhibited full megakaryocytic differentiation, manifested by
      adhesion, shape change, increased cell size, polyploidy, PPF, and expression of
      CD41(+), CD61(+), and CD62P(+). The same morphologic and phenotypic features were
      observed in serum-free cultures in the presence of FN/PMA. Only partial
      differentiation occurred when other integrin ligands were substituted for FN. FN
      alone induced minimal cell adhesion and spreading, while PMA alone induced only
      polyploidy without adhesion. Signal transduction changes involved the activation
      of the extracellular signal-regulated protein kinase 1 (ERK1)/ERK2 as well as c
      Jun amino-terminal kinase 1 (JNK1)/stress-activated protein kinase (SAPK).
      Phosphoinositide-3 kinase and p38 were not stimulated under these conditions.
      Inhibitors were used to identify the causal relationship between signaling
      pathways and PPF. PD98059 and GF109203X, inhibitors of ERK1/ERK2 pathway and PKC,
      respectively, blocked PPF, while adhesion, spreading, and polyploidy were normal.
      These studies show that activation of ERK1/ERK2 mitogen-activated protein kinase
      pathway plays a critical role in PPF. The elucidation of the signal transduction
      pathway on megakaryocyte development and PPF is of crucial importance for
      understanding this unique biological process.

PMID- 11986212
TI  - Factor XII interacts with the multiprotein assembly of urokinase plasminogen
      activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes.
AB  - Investigations were performed to define the factor XII (FXII) binding site(s) on
      cultured endothelial cells (HUVECs). Biotin- or fluorescein isothiocyanate (FITC)
      FXII in the presence of 10 microM Zn(2+) specifically binds to HUVEC monolayers
      or cells in suspension. Collagen-stimulated platelets release sufficient Zn(2+)
      to support FXII binding. On laser scanning confocal microscopy or electron
      microscopy, FITC-FXII or Nanogold-labeled FXII, respectively, specifically bind
      to HUVECs. Antibodies to gC1qR, urokinase plasminogen activator receptor (uPAR)
      and, to a lesser extent, cytokeratin 1 (CK1) block FXII binding to HUVECs as
      determined by flow cytometry and soluble or solid phase binding assays. FITC-FXII
      on endothelial cells colocalizes with gC1qR, uPAR and, to a lesser extent, CK1
      antigen. Combined recombinant soluble uPAR and CK1 inhibit 80% FITC-FXII binding
      to HUVECs. Peptide Y(39)HKCTHKGR(47) (YHK9) from the N-terminal region of FXII
      and peptide H(479)KHGHGHGKHKNKGKKNGKH(498) from HK's domain 5 cell-binding site
      block FITC-FXII binding to HUVECs. Peptide YHK9 also inhibits FXIIa's activation
      of prekallikrein and FXI on HUVECs. These combined investigations indicate that
      FXII through a region on its fibronectin type II domain binds to the same
      multiprotein receptor complex that comprises the HK binding site of HUVECs.
      However, plasma concentrations of HK and vitronectin inhibit FXII binding to
      HUVECs 100% and 50%, respectively, and plasma albumin and other proteins prevent
      a sufficient level of free Zn(2+) to be available to support FXII binding to
      HUVECs. Thus, physiologic FXII expression on HUVECs is secondary to HK binding
      and highly restricted in its ability to initiate prekallikrein or FXI activation.

PMID- 11986213
TI  - Fibrinogen Hillsborough: a novel gammaGly309Asp dysfibrinogen with impaired
      clotting.
AB  - We present a novel gamma-chain dysfibrinogen that was discovered in a 32-year-old
      asymptomatic man admitted to the hospital after a car accident. He presented with
      a low fibrinogen concentration, 0.5 mg/mL, and a prolonged thrombin clotting
      time, 58 seconds. Analysis of purified fibrinogen by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed a gamma-chain variant with an
      apparently higher molecular weight. Isoelectric focusing (IEF) demonstrated an
      anodal shift in the banding pattern of the chains and electrospray ionization
      mass spectrometry (ESIMS) showed a 27-Da increase in the average mass of the
      unresolved variant and normal gamma chains. DNA sequence analysis showed a
      heterozygous mutation of GGC (Gly)-->GAC (Asp) at codon 309 of the gamma chain
      gene. This Gly--> Asp substitution was consistent with the charge change shown by
      IEF as well as the mass change identified by ESIMS. Functional analysis revealed
      that thrombin-catalyzed polymerization occurred with a longer lag time, lower
      rate of lateral aggregation, and similar final turbidity compared to normal and
      that factor XIII cross-linking was normal. The polymerization results suggest
      that residue gamma309 is necessary for proper alignment of fibrinogen molecules,
      specifically in protofibril formation and D:D interactions. gammaGly309 is highly
      conserved and x-ray structures support the conclusion that the lack of a side
      chain at this position helps facilitate the close contact between abutting gammaD
      domains of condensing fibrin monomers during polymerization.

PMID- 11986214
TI  - Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the
      salivary gland of the tick, Ixodes scapularis: identification of factor X and
      factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex.
AB  - Saliva of the hard tick and Lyme disease vector, Ixodes scapularis, has a
      repertoire of compounds that counteract host defenses. Following sequencing of an
      I scapularis salivary gland complementary DNA (cDNA) library, a clone with
      sequence homology to tissue factor pathway inhibitor (TFPI) was identified. This
      cDNA codes for a mature protein, herein called Ixolaris, with 140 amino acids
      containing 10 cysteines and 2 Kunitz-like domains. Recombinant Ixolaris was
      expressed in insect cells and shown to inhibit factor VIIa (FVIIa)/tissue factor
      (TF)-induced factor X (FX) activation with an inhibitory concentration of 50%
      (IC(50)) in the picomolar range. In nondenaturing gel, Ixolaris interacted
      stoichiometrically with FX and FXa but not FVIIa. Ixolaris behaves as a fast-and
      tight ligand of the exosites of FXa and gamma-carboxyglutamic acid domainless FXa
      (des-Gla-FXa), increasing its amidolytic activity. At high concentration,
      Ixolaris attenuates the amidolytic activity of FVIIa/TF; however, in the presence
      of DEGR-FX or DEGR-FXa (but not des-Gla-DEGR-FXa), Ixolaris becomes a tight
      inhibitor of FVIIa/TF as assessed by recombinant factor IX (BeneFIX) activation
      assays. This indicates that FX and FXa are scaffolds for Ixolaris in the
      inhibition of FVIIa/TF and implies that the Gla domain is necessary for
      FVIIa/TF/Ixolaris/FX(a) complex formation. Additionally, we show that Ixolaris
      blocks FXa generation by endothelial cells expressing TF. Ixolaris may be a
      useful tool to study the structural features of FVIIa, FX, and FXa, and an
      alternative anticoagulant in cardiovascular diseases.

PMID- 11986215
TI  - Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the
      endocytic machinery, resulting in retention of low-density lipoprotein on the
      cell surface.
AB  - The influence of platelets on the cellular metabolism of atherogenic lipoproteins
      has not been characterized in detail. Therefore, we investigated the effect of
      platelet factor 4 (PF4), a cationic protein released in high concentration by
      activated platelets, on the uptake and degradation of low-density lipoprotein
      (LDL) via the LDL receptor (LDL-R). LDL-R-dependent binding, internalization, and
      degradation of LDL by cultured cells were inhibited 50%, 80%, and 80%,
      respectively, on addition of PF4. PF4 bound specifically to the ligand-binding
      domain of recombinant soluble LDL-R (half-maximal binding 0.5 microg/mL PF4) and
      partially (approximately 50%) inhibited the binding of LDL. Inhibition of
      internalization and degradation by PF4 required the presence of cell-associated
      proteoglycans, primarily those rich in chondroitin sulfate. PF4 variants with
      impaired heparin binding lacked the capacity to inhibit LDL. PF4, soluble LDL-R,
      and LDL formed ternary complexes with cell-surface proteoglycans. PF4 induced the
      retention of LDL/LDL-R complexes on the surface of human fibroblasts in
      multimolecular clusters unassociated with coated pits, as assessed by immuno
      electron microscopy. These studies demonstrate that PF4 inhibits the catabolism
      of LDL in vitro in part by competing for binding to LDL-R, by promoting
      interactions with cell-associated chondroitin sulfate proteoglycans, and by
      disrupting the normal endocytic trafficking of LDL/LDL-R complexes. Retention of
      LDL on cell surfaces may facilitate proatherogenic modifications and support an
      expanded role for platelets in the pathogenesis of atherosclerosis.

PMID- 11986216
TI  - Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF
      monoclonal antibody results in abolition of in vivo arterial platelet thrombus
      formation in baboons.
AB  - The interaction between collagen, von Willebrand factor (VWF), and glycoprotein
      Ib is the first step in hemostasis and thrombosis especially under high shear
      conditions. We studied the inhibition of the VWF-collagen interaction by using an
      antihuman VWF monoclonal antibody 82D6A3 to prevent arterial thrombosis in
      baboons to develop a new kind of antithrombotic strategy and determine for the
      first time experimental in vivo data concerning the importance of the collagen
      VWF interaction. We used a modified Folts model to study the antithrombotic
      efficacy of 82D6A3, where cyclic flow reductions (CFRs) were measured in the
      femoral artery. Administering a dose of 100, 300, and 600 microg/kg resulted in a
      58.3%, 100%, and 100% reduction in the CFRs, respectively. When 100 microg/kg
      82D6A3 was infused into the baboons, 80% of VWF-A3 domain was occupied,
      corresponding to 30% to 36% ex vivo inhibition of VWF binding to collagen, with
      no prolongation of the bleeding time. The bleeding time was also not
      significantly prolonged when the CFRs were abolished at doses of 300 microg/kg
      and 600 microg/kg. At these doses 100% of VWF was occupied by the antibody and
      100% ex vivo inhibition of the VWF-collagen binding was observed. 82D6A3 has a
      high affinity for VWF; after 48 hours still 68% VWF (300 microg/kg) was occupied
      with a pharmacologic effect up to 5 hours after administration (80%-100%
      occupancy). In conclusion, these results clearly indicate that the VWF-collagen
      interaction is important in vivo in thrombosis under high shear conditions and
      thus might be a new target for preventing arterial thrombosis.

PMID- 11986217
TI  - Protease-activated receptors 1 and 4 do not stimulate G(i) signaling pathways in
      the absence of secreted ADP and cause human platelet aggregation independently of
      G(i) signaling.
AB  - Thrombin is an important agonist for platelet activation and plays a major role
      in hemostasis and thrombosis. Thrombin activates platelets mainly through
      protease-activated receptor 1 (PAR1), PAR4, and glycoprotein Ib. Because
      adenosine diphosphate and thromboxane A(2) have been shown to cause platelet
      aggregation by concomitant signaling through G(q) and G(i) pathways, we
      investigated whether coactivation of G(q) and G(i) signaling pathways is the
      general mechanism by which PAR1 and PAR4 agonists also activate platelet
      fibrinogen receptor (alphaIIbbeta3). A PAR1-activating peptide, SFLLRN, and PAR4
      activating peptides GYPGKF and AYPGKF, caused inhibition of stimulated adenylyl
      cyclase in human platelets but not in the presence of either Ro 31-8220, a
      protein kinase C selective inhibitor that abolishes secretion, or AR-C66096, a
      P2Y12 receptor-selective antagonist; alpha-thrombin-induced inhibition of
      adenylyl cyclase was also blocked by Ro 31-8220 or AR-C66096. In platelets from a
      P2Y12 receptor-defective patient, alpha-thrombin, SFLLRN, and GYPGKF also failed
      to inhibit adenylyl cyclase. In platelets from mice lacking the P2Y12 receptor,
      neither alpha-thrombin nor AYPGKF caused inhibition of adenylyl cyclase.
      Furthermore, AR-C66096 caused a rightward shift of human platelet aggregation
      induced by the lower concentrations of alpha-thrombin and AYPGKF but had no
      effect at higher concentrations. Similar results were obtained with platelets
      from mice deficient in the P2Y12. We conclude that (1) thrombin- and thrombin
      receptor-activating peptide-induced inhibition of adenylyl cyclase in platelets
      depends exclusively on secreted adenosine diphosphate that stimulates G(i)
      signaling pathways and (2) thrombin and thrombin receptor-activating peptides
      cause platelet aggregation independently of G(i) signaling.

PMID- 11986218
TI  - Tissue-type plasminogen activator (t-PA) is stored in Weibel-Palade bodies in
      human endothelial cells both in vitro and in vivo.
AB  - Vascular endothelial cells are thought to be the main source of plasma tissue
      type plasminogen activator (t-PA) and von Willebrand factor (VWF). Previous
      studies have suggested that both t-PA and VWF are acutely released in response to
      the same stimuli, both in cultured endothelial cells and in vivo. However, the
      subcellular storage compartment in endothelial cells has not been definitively
      established. We tested the hypothesis that t-PA is localized in Weibel-Palade
      (WP) bodies, the specialized endothelial storage granules for VWF. In cultured
      human umbilical vein endothelial cells (HUVECs), t-PA was expressed in a minority
      of cells and found in WP bodies by immunofluorescence. After up-regulation of t
      PA synthesis either by vascular endothelial growth factor (VEGF) and retinoic
      acid or by sodium butyrate, there was a large increase in t-PA-positive cells. t
      PA was exclusively located to WP bodies, an observation confirmed by
      immunoelectron microscopy. Incubation with histamine, forskolin, and epinephrine
      induced the rapid, coordinate release of both t-PA and VWF, consistent with a
      single storage compartment. In native human skeletal muscle, t-PA was expressed
      in endothelial cells from arterioles and venules, along with VWF. The 2 proteins
      were found to be colocalized in WP bodies by immunoelectron microscopy. These
      data indicate that t-PA and VWF are colocalized in WP bodies, both in HUVECs and
      in vivo. Release of both t-PA and VWF from the same storage pool likely accounts
      for the coordinate increase in the plasma level of the 2 proteins in response to
      numerous stimuli, such as physical activity, beta-adrenergic agents, and 1
      deamino-8d-arginine vasopressin (DDAVP) among others.

PMID- 11986219
TI  - Naturally occurring mutations in the thrombomodulin gene leading to impaired
      expression and function.
AB  - Sporadic mutations in the thrombomodulin (TM) gene occur in patients with both
      arterial and venous thrombosis, but the effects of these mutations on expression
      and function are largely unexplored. Full-length wild-type TM complementary DNA
      (cDNA) was incorporated into vector pcDNA6 for transfection into COS-7 cells for
      transient expression. Mutagenesis was performed to create 7 TM mutants with
      natural mutations either previously identified (Ala25Thr, Gly61Ala, Asp468Tyr,
      Pro477Ser, Pro483Leu) or reported here (an 11-base pair [bp] deletion, del791
      801, leading to STOP306, and a missense mutation, Arg385Ser). Four mutations were
      found to detrimentally affect the level of expression of the TM protein. Of the
      missense mutations, 3 had reduced expression compared to wild-type TM (100%),
      Arg385Ser (50.2% +/- 5%, P <.001), Pro477Ser (76.8% +/- 1%, P <.001), Pro483Leu
      (82.1% +/- 8%, P <.007). No TM protein expression could be detected on the cell
      surface for mutation del791-801. The cofactor activity of TM in protein C
      activation was also evaluated. The Michaelis constant (K(m)) for wild-type
      thrombin-TM complex was 634 +/- 6 nmol/L. Two mutants, with Arg385Ser and
      Pro477Ser, had increased (P <.0001) K(m), 2967 +/- 283 nM, and 2342 +/- 219 nM,
      respectively, demonstrating impaired function of the thrombin-TM complex. This
      work presents biochemical evidence that certain (but not all) natural mutations
      in the TM gene reduce expression and impair function of the protein on the cell
      surface, and helps clarify the suggested contribution that these mutations might
      make to the risk of thromboembolic disease.

PMID- 11986220
TI  - Analysis of fibrinogen gamma-chain truncations shows the C-terminus, particularly
      gammaIle387, is essential for assembly and secretion of this multichain protein.
AB  - To examine the role of the fibrinogen gamma chain in the assembly and secretion
      of this multichain protein, we synthesized a series of fibrinogen variants with
      truncated gamma chains, terminating between residues gamma379 and the C-terminus,
      gamma411. The variant fibrinogens were synthesized from altered gamma-chain
      complementary DNAs in cultured Chinese hamster ovary cells. Immunoassays of the
      culture media demonstrated that only those variants with gamma chain longer than
      386 residues were secreted and that the concentration of fibrinogen decreased
      with the length of the gamma chain, from 1.4 microg/mL for normal fibrinogen to
      0.39 microg/mL for gamma 387 fibrinogen. Immunoassays of cell lysates showed that
      all variant gamma chains were synthesized, although the levels varied
      significantly. For variants longer than 386 residues, levels decreased with
      length but remained near normal. In contrast, expression of the 4 variants with
      386 residues or less was about 20-fold reduced. Quantitative reverse
      transcription-polymerase chain reaction demonstrated that the gamma-chain
      messenger RNA level was independent from chain length. Western blot analyses
      showed that lysates expressing variants with 387 residues or more contained
      species comparable to the known intermediates in fibrinogen assembly, including
      half-molecules. For shorter variants, these intermediates were not evident. We
      conclude that residues near the C-terminus of the gamma chain are essential for
      fibrinogen assembly, and more specifically, that gamma387 is critical. We propose
      that the loss of residue gamma387 destabilized the structure of gamma chain,
      preventing assembly of alphagamma and betagamma dimers, essential intermediates
      in the assembly of normal fibrinogen.

PMID- 11986221
TI  - Defective expression and function of natural killer cell-triggering receptors in
      patients with acute myeloid leukemia.
AB  - The cytolytic function of natural killer (NK) cells is induced by the engagement
      of a series of activating receptors and coreceptors some of which have recently
      been identified and collectively termed natural cytotoxicity receptors (NCRs).
      Here, we analyzed the cytolytic function of NK cells obtained from patients with
      acute myeloid leukemia (AML). In sharp contrast with healthy donors, in most (16
      of 18) patients with AML the majority of NK cells displayed low NCR surface
      density (NCR(dull)). This phenotype correlated with a weak cytolytic activity
      against autologous leukemic cells that could not be reversed by the monoclonal
      antibody-mediated disruption of HLA class I/killer immunoglobulinlike receptor
      interaction. The remaining 2 patients were characterized by NK cells having an
      NCR(bright) phenotype. Surprisingly, although displaying NCR-mediated cytolytic
      activity, these NCR(bright) NK cells were unable to kill autologous leukemic
      blasts. Importantly, the leukemic blasts from these 2 patients were also
      resistant to lysis mediated by normal NCR(bright) allogeneic NK cells. Our study
      suggests that in most instances the inability of NK cells to kill autologous
      leukemic blasts is consequent to low NCR surface expression. In few cases,
      however, this failure appears to involve a mechanism of tumor escape based on
      down-regulation of ligands relevant for NCR-mediated target cell recognition.

PMID- 11986222
TI  - Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different
      immunosuppressive regimens.
AB  - We studied the degree and the pattern of skewing of the variable region of beta
      chain (VB) T-cell receptor (TCR) repertoire in aplastic anemia (AA) at initial
      presentation and after immunosuppression using a high-resolution analysis of the
      TCR VB complementarity-determining region 3 (CDR3). Age-matched healthy
      individuals and multitransfused patients with non-immune-mediated hematologic
      diseases were used as controls. In newly diagnosed AA, the average frequency of
      CDR3 size distribution deviation indicative of oligoclonal T-cell proliferation
      was increased (44% +/- 33% vs 9% +/- 9%; P =.0001); AA patients with human
      leukocyte antigen (HLA)-DR2 and those with expanded paroxysmal nocturnal
      hemoglobinuria clones showed more skewed VB repertoires. Nonrandom oligoclonal
      patterns were found for VB6, VB14-16, VB21, VB23, and VB24 subfamilies in more
      than 50%, and for VB15, VB21, and VB24 in more than 70% of AA patients with HLA
      DR2. Patients received immunosuppression with antithymocyte globulin
      (ATG)/cyclosporine (CsA) or cyclophosphamide (CTX) with CsA in combination, and
      their VB repertoire was reanalyzed after treatment. Whereas no significant change
      in the degree of VB skewing in patients who had received ATG was seen, patients
      treated with CTX showed a much higher extent of oligoclonality within all VB
      families, consistent with a profound and long-lasting contraction of the T-cell
      repertoire. VB analysis did not correlate with the lymphocyte count prior to
      lymphocytotoxic therapy; however, after therapy the degree of VB skewing was
      highly reflective of the decrease in lymphocyte numbers, suggesting iatrogenic
      gaps in the VB repertoire rather than the emergence of clonal dominance. Our data
      indicate that multiple specific clones mediate the immune process in AA.

PMID- 11986223
TI  - Human platelets express heat shock protein receptors and regulate dendritic cell
      maturation.
AB  - Immunizations using the endoplasmic reticulum-resident heat shock protein Gp96
      induce specific immune responses. Specificity is based on the major
      histocompatibility complex class I-restricted cross-presentation of Gp96
      associated peptides derived from endogenous proteins. Initiation of the immune
      response depends on the ability of Gp96 to induce the production of
      proinflammatory cytokines by macrophages and dendritic cells (DCs) and of their
      maturation in a fashion presumably independent of associated peptide. Both events
      are mediated by Gp96 receptors on antigen-presenting cells. It is known that Gp96
      is released from cells at necrosis induced, for example, by virus infection.
      Although this event supports the efficient induction of immune responses, it
      might also interfere with processes that are susceptible to chronic inflammation,
      such as wound healing after tissue damage. Therefore, Gp96-mediated stimulation
      of the immune system requires tight regulation. Here we show that human
      thrombocytes specifically interact with Gp96 and that binding of Gp96 to
      platelets is enhanced more than 10-fold on activation by thrombin. Gp96
      interferes with neither thrombin-induced platelet activation nor platelet
      aggregation. However, the presence of platelets during Gp96-mediated DC
      activation reduces the secretion of proinflammatory cytokines and the activation
      of DCs. This effect is independent of soluble platelet factors and cell-to-cell
      contact between DCs and thrombocytes. Thus, we provide evidence for a regulatory
      mechanism that neutralizes Gp96 molecules systemically, especially in the blood.
      This effect might be of significance in wounds in which chronic inflammation and
      immune responses against autoantigens have to be prevented.

PMID- 11986224
TI  - Constitutive nuclear factor-kappaB activity preserves homeostasis of quiescent
      mature lymphocytes and granulocytes by controlling the expression of distinct Bcl
      2 family proteins.
AB  - Constitutive nuclear factor kappaB (NF-kappaB) activity protects quiescent mature
      immune cells from spontaneous apoptosis. Here, we examined whether NF-kappaB
      exerts its antiapoptotic function in these cells through the control of Bcl-2
      family proteins. Specific pharmacologic inhibitors of NF-kappaB were used to
      achieve total NF-kappaB inactivation in quiescent human blood lymphocytes,
      granulocytes, and monocytes. NF-kappaB inhibition induced drastic lymphocyte and
      granulocyte apoptosis, but only moderate monocyte apoptosis. T- and B-cell
      apoptosis was slow and associated with a gradual down-regulation of the
      prosurvival Bcl-2 family proteins Bcl-x(L) and Bcl-2, respectively. By contrast,
      granulocyte apoptosis was fast and accompanied by a rapid cellular accumulation
      of Bcl-x(S), the proapoptotic Bcl-x isoform that is generated from alternative
      splicing of the bcl-x pre-mRNA. Finally, antisense bcl-x(L) and bcl-2 knockdown
      in T and B cells, respectively, and induction of Bcl-x(S) expression in
      granulocytes through antisense oligonucleotide-mediated redirection of bcl-x pre
      mRNA splicing were sufficient to induce significant apoptosis in these cells.
      Taken together, these results reveal that basal NF-kappaB activity preserves
      homeostasis of quiescent mature lymphocytes and granulocytes through regulation
      of distinct members of the Bcl-2 family. This study sheds light on the
      constitutive mechanisms by which NF-kappaB maintains defense integrity.

PMID- 11986225
TI  - Differential abilities of central nervous system resident endothelial cells and
      astrocytes to serve as inducible antigen-presenting cells.
AB  - Microglial cells and astrocytes are capable of processing and presenting antigens
      for efficient activation of T cells. However, the antigen-presenting function and
      role of cerebrovascular endothelial cells (CVEs) in central nervous system
      inflammatory responses remain controversial. We compared the expression of
      necessary accessory molecules and the functional antigen-presenting capacity of
      cloned SJL/J CVEs and primary astrocytes in response to the pro-inflammatory
      cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF
      alpha). Astrocytes and CVEs up-regulated major histocompatibility complex (MHC)
      class II, and primarily B7-1 as opposed to B7-2, in response to IFN-gamma. TNF
      alpha inhibited the IFN-gamma-induced up-regulation of MHC class II on CVEs
      correlating to a decrease in the mRNA for the class II transactivator (CIITA),
      whereas CIITA expression in astrocytes was unaffected. Unlike astrocytes, CVEs
      did not elicit significant MHC class II-restricted T-cell responses. Furthermore,
      we have found that CVE monolayers are altered following T-cell contact,
      implicating CVE/T-cell contact in the breakdown of the blood-brain barrier during
      neuro-inflammatory responses.

PMID- 11986226
TI  - T-cell repopulation and thymic volume in HIV-1-infected adult patients after
      highly active antiretroviral therapy.
AB  - The origin of T cells after highly active antiretroviral therapy (HAART) in
      patients infected with human immunodeficiency virus 1 (HIV-1) is now under
      discussion. The possibility of renewed lymphopoiesis in aged thymuses is still
      controversial. In this work we combine the analysis of naive T cells, T-cell
      receptor excision circles (TRECs), and computed tomography scanning of thymic
      tissue to further assess whether the thymus is involved in immune reconstitution.
      Fifteen antiretroviral-naive HIV-1-infected patients were evaluated during 48
      weeks of HAART. At baseline, significant correlation was present among age and
      both thymic volume and TRECs, and between naive T cells and TRECs. After starting
      HAART, there was a significant increase at week 12 in naive CD4(+) and CD8(+) T
      cells, TRECs, and thymic volume. The initial net increases in naive T cells and
      TREC counts were significantly correlated. Changes in thymic volume and TRECs
      were also indirectly related; splitting the population into 2 groups of high and
      low baseline TREC levels, only the group with low TREC levels had significant
      increases in both TRECs and thymic volume. Thus, the increase in thymic volume
      might be functional, in response to depleted TREC levels. Taken together, our
      data strongly suggest a thymic role in immune reconstitution, at least in
      patients with depleted baseline TREC levels. (Blood. 2002;99:3702-3706)

PMID- 11986227
TI  - Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in
      vivo from spontaneous complement attack.
AB  - Decay-accelerating factor (DAF) and CD59 are 2 glycosylphosphatidylinositol
      anchored membrane proteins that inhibit complement activation at the C3 and C5b-9
      step, respectively. CD59 is considered critical for protecting erythrocytes from
      spontaneous complement attack, as deficiency of CD59 or CD59/DAF, but not of DAF
      alone, on human erythrocytes renders them sensitive to complement lysis in
      paroxysmal nocturnal hemoglobinuria syndrome. To evaluate the relative roles of
      CD59 and DAF in vivo, we have generated and studied a CD59 knockout and a
      CD59/DAF double-knockout mouse. CD59-deficient and CD59/DAF-double-deficient
      mouse erythrocytes were highly sensitive to antibody-induced complement lysis in
      vitro, yet neither CD59 knockout nor CD59/DAF double-knockout mouse developed
      spontaneous hemolytic anemia. Consistent with the latter observation,
      erythrocytes from the 2 strains of mutant mice were shown to have a normal
      lifespan in vivo. In contrast, mouse erythrocytes deficient in complement
      receptor 1 (CR1)-related gene y (Crry), a membrane C3 inhibitor with DAF and
      membrane cofactor protein activities, were rapidly eliminated from the
      circulation by a complement-dependent mechanism. Compared with DAF-deficient
      erythrocytes, Crry-deficient erythrocytes incurred higher levels of spontaneous
      C3 deposition in vivo. These findings demonstrate that CD59 and DAF are not
      indispensable on murine erythrocytes. Rather, effective C3 regulation on the cell
      surface, provided by Crry rather than DAF, is necessary for mouse erythrocytes to
      resist spontaneous complement attack. Our results raise the possibility that
      proper control of C3 activation may also be critical on human erythrocytes, where
      CR1 but not DAF could be the principal regulator of spontaneous C3 activation.

PMID- 11986228
TI  - Presentation of a major histocompatibility complex class 1-binding peptide by
      monocyte-derived dendritic cells incorporating hydrophobized polysaccharide
      truncated HER2 protein complex: implications for a polyvalent immuno-cell
      therapy.
AB  - Recognition of the essential role of dendritic cells (DCs) as professional
      antigen-presenting cells has prompted investigators to search for methods to use
      DCs as natural adjuvants in immunotherapy. A number of antigenic oligopeptides,
      recognized by CD8(+) cytotoxic T lymphocytes (CTLs) specific for cancer cells,
      have been applied in clinical trials using DCs. Such a monovalent vaccine with a
      single epitope for a particular type of HLA class 1 molecule would be effective.
      However, a polyvalent vaccine might be more potent. We designed a novel protein
      delivery system consisting of hydrophobized polysaccharides complexed with target
      proteins. The truncated HER2 protein encompassing 147 N-terminal amino acids,
      including the 9-mer HER2p63-71 peptide (HER2p63), TYLPTNASL, the human homologue
      of an antigenic murine tumor rejection peptide, was prepared. We report here that
      HLA-A2402(+) DCs could incorporate hydrophobized polysaccharide-truncated HER2
      protein complexes and process the protein to present major histocompatibility
      complex class 1-binding HER2p63 peptide. The complexes enter DCs by phagocytosis,
      and then the truncated protein is processed through a pathway similar to that for
      endogenous proteins. DCs sensitized by these complexes primed and boosted HER2p63
      specific CD8(+) T cells in the context of HLA-A2402. Vaccination with DCs
      incorporating these complexes completely suppressed lung metastases in a HER2
      expressing murine tumor model. We also generated 3 CD4(+) clones reactive with
      different HER2- derived 25-mer peptides from lymph node cells in mice treated
      with CHP/HER2-147. Thus, hydrophobized polysaccharide-protein complexes are
      promising candidates for the construction of polyvalent vaccines.

PMID- 11986229
TI  - Epstein-Barr virus inhibits the development of dendritic cells by promoting
      apoptosis of their monocyte precursors in the presence of granulocyte macrophage
      colony-stimulating factor and interleukin-4.
AB  - Epstein-Barr virus (EBV) is a tumorigenic human herpesvirus that persists for
      life in healthy immunocompetent carriers. The viral strategies that prevent its
      clearance and allow reactivation in the face of persistent immunity are not well
      understood. Here we demonstrate that EBV infection of monocytes inhibits their
      development into dendritic cells (DCs), leading to an abnormal cellular response
      to granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4
      (IL-4) and to apoptotic death. This proapoptotic activity was not affected by UV
      inactivation and was neutralized by EBV antibody-positive human sera, indicating
      that binding of the virus to monocytes is sufficient to alter their response to
      the cytokines. Experiments with the relevant blocking antibodies or with mutated
      EBV strains lacking either the EBV envelope glycoprotein gp42 or gp85
      demonstrated that interaction of the trimolecular gp25-gp42-gp85 complex with the
      monocyte membrane is required for the effect. Our data provide the first evidence
      that EBV can prevent the development of DCs through a mechanism that appears to
      bypass the requirement for viral gene expression, and they suggest a new strategy
      for interference with the function of DCs during the initiation and maintenance
      of virus-specific immune responses.

PMID- 11986230
TI  - Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique
      subset of patients.
AB  - The t(11;14)(q13;q32) results in up-regulation of cyclin D1 and is the most
      common translocation detected in multiple myeloma, where it is also associated
      with a lymphoplasmacytic morphology. We performed an interphase fluorescent in
      situ hybridization (FISH) study to determine the clinical and biologic
      significance of the abnormality when testing a large cohort of myeloma patients.
      Bone marrow slides from multiple myeloma patients entered into the Eastern
      Cooperative Oncology Group phase III clinical trial E9486 and associated
      laboratory correlative study E9487 were analyzed using interphase FISH combined
      with immune-fluorescent (cytoplasmic immunoglobulin-FISH) detection of clonal
      plasma cells. We used FISH probes that hybridize to the 14q32 and 11q13
      chromosomal loci. The t(11;14)(q13;q32) was correlated with known biologic and
      prognostic factors. Of 336 evaluable patients, 53 (16%) had abnormal FISH
      patterns compatible with the t(11;14)(q13;q32). These patients appeared to be
      more likely to have a serum monoclonal protein of less than 10 g/L (1 g/dL) (28%
      vs 15%, P =.029) and a lower plasma cell labeling index (P =.09). More
      strikingly, patients were less likely to be hyperdiploid by DNA content analysis
      (n = 251, 14% vs 62%, P <.001). Patients with the t(11;14)(q13;q32) appeared to
      have better survival and response to treatment, although this did not reach
      statistical significance. Multiple myeloma with the t(11;14)(q13;q32) is a unique
      subset of patients, not only characterized by cyclin D1 up-regulation and a
      lymphoplasmacytic morphology, but is also more frequently associated with small
      serum monoclonal proteins and is much less likely to be hyperdiploid. These
      patients do not have a worsened prognosis as previously thought.

PMID- 11986231
TI  - Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic
      leukemia.
AB  - Members of the Notch family encode transmembrane receptors that modulate
      differentiation, proliferation, and apoptotic programs of many precursor cells,
      including hematopoietic progenitors. Stimulation of Notch causes cleavage
      followed by translocation of the intracellular domain (NotchIC) to the nucleus,
      where it activates transcription of CBF1 responsive genes. The aim of this study
      was to elucidate the mechanisms leading to the overexpression of CD23, a striking
      feature of B-cell chronic lymphocytic leukemia (B-CLL) cells. By electrophoretic
      mobility shift assays, we identified a transcription factor complex (C1) that
      binds sequence specific to one known and 4 newly identified putative CBF1
      recognition sites in the CD23a core promoter region. With the use of Epstein-Barr
      virus (EBV)-infected B cells as a model for CBF1 mediated CD23a expression, C1
      was found to be EBV inducible. Supershift assays revealed that the nuclear form
      of Notch2 is a component of C1 in B-CLL cells, supporting a model in which
      NotchIC activates transcription by binding to CBF1 tethered to DNA. Transient
      transfection of REH pre-B cells with an activated form of Notch2 induced
      endogenous CD23a, confirming that CD23a is a target gene of Notch2 signaling.
      Finally, reverse transcription-polymerase chain reaction and kinetic analysis
      demonstrated that the Notch2 oncogene is not only overexpressed in B-CLL cells
      but might also be related to the failure of apoptosis characteristic for this
      disease. In conclusion, these data suggest that deregulation of Notch2 signaling
      is involved in the aberrant expression of CD23 in B-CLL.

PMID- 11986232
TI  - Vaccination with CD20 peptides induces a biologically active, specific immune
      response in mice.
AB  - CD20 is a 33-kD B-cell antigen that is expressed from the early pre-B-cell stage
      of development and is lost on differentiation of B cells into plasma cells.
      Because CD20 is expressed strictly by B cells, it is an attractive target for B
      cell lymphoma therapy. Monoclonal antibodies to CD20 have been used successfully
      in the treatment of B-cell lymphomas. We hypothesized that a vaccine consisting
      of CD20 peptide sequences might be capable of inducing an active, specific,
      humoral immune response to the protein. Vaccine therapy would have the advantage
      of generating a polyclonal response to the antigen in contrast to the monoclonal
      response of an infused antibody. Balb/c mice were vaccinated with prototype
      vaccine constructs that consisted of peptides representing the human or mouse
      CD20 extracellular sequences conjugated to carrier proteins and mixed with QS21
      adjuvant. Sera from the vaccinated mice demonstrated high-titer, specific
      antibodies to various epitopes on the immunizing peptides in enzyme-linked
      immunosorbent assay, weaker antibody binding to native CD20 on cells by flow
      cytometry, and antibody-mediated complement killing of CD20(+) cells in some
      cases. Specific proliferation and secretion of interleukin 4 and interferon gamma
      by mouse spleen cells in response to the immunizing peptides were also
      demonstrated. Mice vaccinated with the CD20 peptide keyhole limpet hemocyanin
      conjugates had a 25% decrease in CD19(+) splenic B cells relative to control
      mice. These data indicate that a biologically active, specific immune response to
      CD20 can be elicited in mice vaccinated with CD20 peptide conjugates.

PMID- 11986233
TI  - Interleukin-21 is a growth and survival factor for human myeloma cells.
AB  - Interleukin-21 (IL-21) is a recently cloned cytokine with homology to IL-2, IL-4,
      and IL-15. In this study we examined the effects of IL-21 on human myeloma cells.
      We found that IL-21 induced proliferation and inhibited apoptosis of the IL-6
      dependent human myeloma cell lines ANBL-6, IH-1, and OH-2. The potency of IL-21
      was close to that of IL-6 in the OH-2 cell line. Neutralizing antibodies to IL-6
      or the IL-6 receptor transducer chain (gp130) did not affect IL-21-induced DNA
      synthesis, indicating that IL-21-induced proliferation was not mediated through
      these proteins. Tumor necrosis factor (TNF), another stimulator of myeloma cell
      growth, up-regulated the expression level of IL-21 receptor (IL-21R), and
      combinations of TNF and IL-21 gave synergistic effects on myeloma cell
      proliferation. Furthermore, 4 of 9 purified samples of primary myeloma cells
      showed a significant increase in DNA synthesis on stimulation of the cells by IL
      21. By Western blot analysis, we demonstrated that the intracellular signaling
      pathways of IL-21 in myeloma cells involved phosphorylation of Jak1, Stat3, and
      Erk1/2 (p44/42 mitogen-activated protein kinase). IL-21 is a novel growth and
      survival factor in multiple myeloma and may represent a target for future
      therapy.

PMID- 11986234
TI  - Expression and activity of breast cancer resistance protein (BCRP) in de novo and
      relapsed acute myeloid leukemia.
AB  - Overexpression of the breast cancer resistance protein (BCRP) efflux pump in
      human cancer cell lines results in resistance to a variety of cytostatic agents.
      The aim of this study was to analyze BCRP protein expression and activity in
      acute myeloid leukemia (AML) samples and to determine whether it is up-regulated
      due to clonal selection at relapse/refractory disease. BCRP protein expression
      was measured flow cytometrically with the monoclonal antibodies BXP-34 and BXP-21
      in 20 paired samples of de novo and relapsed/refractory AML. BXP
      34/immunoglobulin G1 ratios were observed of 1.6 +/- 0.5 (mean +/- SD, range 0.8
      2.7) and BXP-21/immunoglobulin G2a ratios of 4.9 +/- 3.0 (range 1.1-14.5) in the
      patient samples versus 9.8 +/- 6.8 and 6.5 +/- 2.4, respectively, in the MCF-7
      cell line. BCRP activity was determined flow cytometrically by measuring
      mitoxantrone accumulation in absence and presence of the inhibitor fumitremorgin
      C. Mitoxantrone accumulation, expressed as mean fluorescence intensity (MFI),
      varied between 44 and 761 MFI (227 +/- 146 MFI) and correlated inversely with
      BCRP expression (r = -0.58, P <.001). Addition of fumitremorgin C showed a small
      increase in mitoxantrone accumulation (11 +/- 29 MFI, n = 40) apart from the
      effect of PSC833 and MK-571. No consistent up-regulation of BCRP expression or
      activity was observed at relapse/refractory disease; some cases showed an
      increase and other cases a decrease at relapse. Relatively high BCRP expression
      correlated with immature immunophenotype, as determined by expression of the
      surface marker CD34 (r = 0.54, P =.001). In conclusion, this study shows that
      BCRP protein is expressed at low but variable levels in AML, especially in
      immature CD34(+) cells. BCRP was not consistently up-regulated in
      relapsed/refractory AML.

PMID- 11986235
TI  - Antitumorigenic effects of HIV protease inhibitor ritonavir: inhibition of Kaposi
      sarcoma.
AB  - Treatment of patients with human immunodeficiency virus (HIV) protease inhibitors
      such as ritonavir can result in increases in CD4(+) T-cell counts that are
      independent of a reduction in HIV-1 viral load. This lack of correlation between
      the 2 has led to the identification of additional effects of ritonavir that
      potentially alter HIV disease pathogenesis. Our previous studies indicated that
      ritonavir directly affects immune cell activation, proliferation, and
      susceptibility to apoptosis. We show here that ritonavir inhibited the activation
      and proliferation of primary endothelial cells and decreased the production of
      tumor necrosis factor alpha (TNF-alpha) interleukin 6 (IL-6), IL-8, and vascular
      endothelial growth factor, factors that all contribute to tumor
      neovascularization and to the development of Kaposi sarcoma (KS) lesions.
      Ritonavir also suppressed the expression of vascular cell adhesion molecule 1,
      intercellular adhesion molecule 1, and E-selectin, which correlated with a
      functional decrease in leukocyte adhesion. Transcriptional activation of nuclear
      factor-kappaB, as induced by the KS-promoting factor TNF-alpha, the HIV-1 Tat
      protein, or the human herpesvirus 8 protein ORF74, was inhibited by ritonavir. KS
      derived cell lines underwent apoptosis in vitro after treatment with ritonavir at
      concentrations that are obtained in clinical therapy (3-15 microM). In a KS mouse
      xenotransplantation model, ritonavir inhibited tumor formation and progression by
      KS-derived cells. Taken together, these data suggest that ritonavir has
      antineoplastic effects that are independent from its ability to inhibit the HIV
      protease.

PMID- 11986236
TI  - The AF10 leucine zipper is required for leukemic transformation of myeloid
      progenitors by MLL-AF10.
AB  - The t(10;11)(p12;q23) chromosomal translocation in human acute myeloid leukemia
      results in the fusion of the MLL and AF10 genes. The latter codes for a novel
      leucine zipper protein, one of many MLL fusion partners of unknown function. In
      this report, we demonstrate that retroviral-mediated transduction of an MLL-AF10
      complementary DNA into primary murine myeloid progenitors enhanced their
      clonogenic potential in serial replating assays and led to their efficient
      immortalization at a primitive stage of myeloid differentiation. Furthermore, MLL
      AF10-transduced cells rapidly induced acute myeloid leukemia in syngeneic or
      severe combined immunodeficiency recipient mice. Structure/function analysis
      showed that a highly conserved 82-amino acid portion of AF10, comprising 2
      adjacent alpha-helical domains, was sufficient for immortalizing activity when
      fused to MLL. Neither helical domain alone mediated immortalization, and deletion
      of the 29-amino acid leucine zipper within this region completely abrogated
      transforming activity. Similarly, the minimal oncogenic domain of AF10 exhibited
      transcriptional activation properties when fused to the MLL or GAL4 DNA-binding
      domains, while neither helical domain alone did. However, transcriptional
      activation per se was not sufficient because a second activation domain of AF10
      was neither required nor competent for transformation. The requirement for alpha
      helical transcriptional effector domains is similar to the oncogenic
      contributions of unrelated MLL partners ENL and ELL, suggesting a general
      mechanism of myeloid leukemogenesis by a subset of MLL fusion proteins, possibly
      through specific recruitment of the transcriptional machinery.

PMID- 11986237
TI  - Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase
      genes and risk of adult acute lymphocytic leukemia.
AB  - We previously reported that 2 polymorphisms in the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) gene at positions C677T and A1298C were associated with lower
      risk of adult acute lymphocytic leukemia (ALL). In the present study, we have
      examined whether polymorphisms in other folate-metabolizing genes play a role in
      ALL susceptibility. Polymorphisms in methionine synthase (MS A2756G), cytosolic
      serine hydroxymethyltransferase (SHMT1 C1420T), and a double (2R2R) or triple
      (3R3R) 28-bp tandem repeat in the promoter region of thymidylate synthase (TS)
      were studied and found to modulate ALL risk. In a univariate analysis, SHMT1
      1420CT individuals exhibited a 2.1-fold decrease in ALL risk (odds ratio [OR] =
      0.48; 95% confidence interval [CI], 0.25-0.91), whereas the 1420TT genotype
      conferred a 3.3-fold reduction in risk (OR = 0.31; 95% CI, 0.10-0.90). Similarly,
      TS 2R3R individuals exhibited a 2.8-fold reduction in ALL risk (OR = 0.36; 95%
      CI: 0.16-0.83), while the TS 3R3R genotype conferred an even greater level of
      protection (OR = 0.25; 95% CI, 0.08-0.78). However, no significant associations
      were evident for the MS 2756AG polymorphism (OR = 0.79; 95% CI, 0.38-1.7). In
      addition, potential interactions between the SHMT1 and TS or MS genes were
      observed. TS 3R3R individuals who were SHMT1 1420CT/TT had a 13.9-fold decreased
      ALL risk (OR = 0.072; 95% CI, 0.0067-0.77). Further, MS 2756AG individuals who
      were SHMT1 1420CT/TT had a 5.6-fold reduction in ALL risk (OR = 0.18; 95% CI,
      0.05-0.63). This study suggests an important role for uracil misincorporation and
      resultant chromosomal damage in the pathogenesis of ALL, and that genetic
      interactions involving low penetrance polymorphisms in folate-metabolizing genes
      may increase ALL risk.

PMID- 11986238
TI  - Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in
      chronic myelogenous leukemia through reversal of abnormally increased
      proliferation.
AB  - Imatinib mesylate (STI571) is a promising new treatment for chronic myelogenous
      leukemia (CML). The effect of imatinib mesylate on primitive malignant
      progenitors in CML has not been evaluated, and it is not clear whether
      suppression of progenitor growth represents inhibition of increased
      proliferation, induction of apoptosis, or both. We demonstrated here that in
      vitro exposure to concentrations of imatinib mesylate usually achieved in
      patients (1-2 microM) for 96 hours inhibited BCR/ABL-positive primitive
      progenitors (6-week long-term culture-initiating cells [LTCICs]) as well as
      committed progenitors (colony-forming cells [CFCs]). No suppression of normal
      LTCICs and significantly less suppression of normal CFCs were observed. A higher
      concentration of imatinib mesylate (5 microM) did not significantly increase
      suppression of CML or normal LTCICs but did increase suppression of CML CFCs, and
      to a lesser extent, normal CFCs. Analysis of cell division using the fluorescent
      dye carboxyfluorescein diacetate succinimidyl ester indicated that imatinib
      mesylate (1-2 microM) inhibits cycling of CML primitive (CD34(+)CD38(-)) and
      committed (CD34(+)CD38(+)) progenitors to a much greater extent than normal
      cells. Conversely, treatment with 1 to 2 microM imatinib mesylate did not
      significantly increase the percentage of cells undergoing apoptosis. Although a
      higher concentration of imatinib mesylate (5 microM) led to an increase in
      apoptosis of CML cells, apoptosis also increased in normal samples. In summary,
      at clinically relevant concentrations, imatinib mesylate selectively suppresses
      CML primitive progenitors by reversing abnormally increased proliferation but
      does not significantly increase apoptosis. These results suggest that inhibition
      of Bcr-Abl tyrosine kinase by imatinib mesylate restores normal hematopoiesis by
      removing the proliferative advantage of CML progenitors but that elimination of
      all CML progenitors may not occur.

PMID- 11986239
TI  - In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid
      leukemia.
AB  - Recent reports have established the prenatal origin of leukemia translocations
      and resultant fusion genes in some patients, including MLL-AF4 translocations in
      infants and TEL-AML1 translocations in children. We now report evidence for the
      prenatal origin of a translocation in childhood acute myeloid leukemia (AML). The
      t(8;21) AML1-ETO translocations were sequenced at the genomic level in 10
      diagnostic leukemia samples from children with available neonatal Guthrie blood
      spots. Clonotypic genomic AML1-ETO sequences were detected in the Guthrie spots
      for 5 individuals, providing unambiguous evidence of prenatal origin in these
      cases. Two of these patients were older than 10 years of age at diagnosis,
      indicative of a protracted postnatal latency. Three of the patients were assessed
      for the persistence of genomic fusion sequences in complete clinical remission
      samples and were found to be positive. These data indicate that t(8;21) in
      childhood AML can arise in utero, possibly as an initiating event in childhood
      AML, and may establish a long-lived or stable parental clone that requires
      additional secondary genetic alterations to cause leukemia.

PMID- 11986240
TI  - Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular
      lymphoma: 2 types of follicular lymphoma grade 3.
AB  - Follicular lymphoma (FL) grades 1 and 2 are regarded as a distinct disease
      entity, whereas data suggest that FL grade 3 might be an inhomogeneous tumor
      category. To define the biologic spectrum of FL, 89 follicular lymphomas were
      studied for their cytologic composition, antigen expression, mitotic and
      proliferation indices, cytogenetics, and clinical data. In contrast to the
      homogeneous appearance of FL grades 1 and 2 (29 and 33 cases, respectively), 2
      types of FL grade 3 were recognized. Eleven cases of FL 3a displayed structural
      features similar to those of FL 1 and 2 and were composed of centroblasts and
      centrocytes, whereas 16 cases of FL 3b, with (n = 4) or without (n = 12) a
      diffuse large B-cell lymphoma component (DLBL) (FL 3b +/- DLBL), consisted
      exclusively of blasts. In contrast to FL 3a, FL 3b +/- DLBL were CD10(+) in only
      50% of cases and displayed plasmacytoid differentiation in 44% of cases. Although
      FL3a was t(14;18)+ in 8 of 11 (73%) cases, only 2 of 16 (13%) FL3b +/- DLBLs
      harbored this translocation. In contrast, chromosomal breaks at 3q27 were
      encountered in 7 of 16 (44%) FL 3b +/- DLBL in contrast to only 2 of 11 (18%) FL
      3a, and the spectrum of secondary aberrations in FL 3b +/- DLBL was similar to
      that of diffuse large B-cell lymphoma. We conclude, therefore, that FL grade 3 is
      a heterogeneous disease group and that the distinction proposed in the new World
      Health Organization classification between FL 3a (with centrocytes) and FL3b
      (without centrocytes) is of biologic, and possibly clinical, importance.

PMID- 11986241
TI  - Erythroid differentiation and protoporphyrin IX down-regulate frataxin expression
      in Friend cells: characterization of frataxin expression compared to molecules
      involved in iron metabolism and hemoglobinization.
AB  - Friedreich ataxia (FA) is caused by decreased frataxin expression that results in
      mitochondrial iron (Fe) overload. However, the role of frataxin in mammalian Fe
      metabolism remains unclear. In this investigation we examined the function of
      frataxin in Fe metabolism by implementing a well-characterized model of erythroid
      differentiation, namely, Friend cells induced using dimethyl sulfoxide (DMSO). We
      have characterized the changes in frataxin expression compared to molecules that
      play key roles in Fe metabolism (the transferrin receptor [TfR] and the Fe
      transporter Nramp2) and hemoglobinization (beta-globin). DMSO induction of
      hemoglobinization results in a marked decrease in frataxin gene (Frda) expression
      and protein levels. To a lesser extent, Nramp2 messenger RNA (mRNA) levels were
      also decreased on erythroid differentiation, whereas TfR and beta-globin mRNA
      levels increased. Intracellular Fe depletion using desferrioxamine or pyridoxal
      isonicotinoyl hydrazone, which chelate cytoplasmic or cytoplasmic and
      mitochondrial Fe pools, respectively, have no effect on frataxin expression.
      Furthermore, cytoplasmic or mitochondrial Fe loading of induced Friend cells with
      ferric ammonium citrate, or the heme synthesis inhibitor, succinylacetone,
      respectively, also had no effect on frataxin expression. Although frataxin has
      been suggested by others to be a mitochondrial ferritin, the lack of effect of
      intracellular Fe levels on frataxin expression is not consistent with an Fe
      storage role. Significantly, protoporphyrin IX down-regulates frataxin protein
      levels, suggesting a regulatory role of frataxin in Fe or heme metabolism.
      Because decreased frataxin expression leads to mitochondrial Fe loading in FA,
      our data suggest that reduced frataxin expression during erythroid
      differentiation results in mitochondrial Fe sequestration for heme biosynthesis.

PMID- 11986242
TI  - Mixed chimerism induces donor-specific T-cell tolerance across a highly disparate
      xenogeneic barrier.
AB  - Induction of tolerance is likely to be essential for successful
      xenotransplantation because immune responses across xenogeneic barriers are
      vigorous. Although mixed hematopoietic chimerism leads to stable donor-specific
      tolerance in allogeneic and closely related xenogeneic (eg, rat-to-mouse)
      combinations, the ability of this approach to induce tolerance across a highly
      disparate xenogeneic barrier has not yet been demonstrated. In this study, we
      investigated the immune responses of murine T cells that developed in mice with
      pre-established porcine hematopoietic chimerism. Our results show for the first
      time that induction of porcine hematopoietic chimerism can eliminate the
      development of antiporcine donor responses in a highly disparate xenogeneic
      species. Porcine hematopoietic chimeras showed donor-specific nonresponsiveness
      in the mixed lymphocyte reaction, lack of antidonor IgG antibody production, and
      acceptance of donor skin grafts. Thus, mixed chimerism is capable of inducing
      tolerance in a highly disparate xenogeneic combination and may have clinical
      potential to prevent xenograft rejection. (Blood. 2002;99:3823-3829)

PMID- 11986243
TI  - Sensitive detection of human cytomegalovirus peptide-specific cytotoxic T
      lymphocyte responses by interferon-gamma-enzyme-linked immunospot assay and flow
      cytometry in healthy individuals and in patients after allogeneic stem cell
      transplantation.
AB  - Reconstitution of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocytes
      (CTLs), predominantly directed against pp65, provides protective immunity for the
      development of HCMV disease after allogeneic stem cell transplantation (SCT). To
      define pp65-derived CTL epitopes that would allow sensitive detection of HCMV
      specific immune reconstitution, a computer-based epitope prediction was
      performed. Peptide-specific CTL responses were assessed by interferon-gamma
      release. With this approach, pp65-derived epitopes presented by the HLA alleles
      A*0101, A*0201, A*1101, and B*0702 were identified. The frequency of CTLs in
      healthy HCMV-seropositive individuals ranged from about 0.1% to 3.3% of all
      CD8(+) T cells. In patients at risk of HCMV infection after allogeneic SCT, HCMV
      peptide-specific CTLs were found in 14 of 19 patients at a median of 90 days
      after SCT (range, 35-234 days) and HCMV-antigen-specific CD4(+) T lymphocytes in
      11 of 18 patients at a median of 90 days after SCT (range, 35->180 days). Peak
      counts of peptide-specific CD8(+) T cells ranged from 0.14 to 60.6 cells/microL;
      those of protein-specific CD4(+) T cells ranged from 0.64 to 18.97 cells/microL.
      Reconstitution of HCMV-peptide-specific CD8(+) T cells and protein-specific
      CD4(+) T cells was associated with clearance of HCMV infection (r(2) = 0.89, P
      <.0001 and r(2) = 0.61, P =.0045, respectively). HCMV infection recurred after
      documentation of HCMV-specific T-cell reconstitution (n = 4) when
      immunosuppression was intensified. Patients in whom late-onset HCMV disease
      developed lacked HCMV-protein-specific T cells at 3 months after SCT. In
      conclusion, prospective monitoring of HCMV-specific CD4(+) and CD8(+) T-cell
      reconstitution can be performed rapidly by using flow cytometry after specific
      stimulation with HCMV peptides and proteins and might help to further improve
      clinical management of HCMV infection after allogeneic SCT.

PMID- 11986244
TI  - Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by
      cellular or nonspecific mitogenic stimuli.
AB  - CD2(+) T lymphocytes obtained from either the donor of bone marrow stromal cells
      (BMSCs) or a third party were cultured in mixed lymphocyte reactions (MLRs) with
      either allogeneic dendritic cells (DCs) or peripheral blood lymphocytes (PBLs).
      When autologous or allogeneic BMSCs were added back to T cells stimulated by DCs
      or PBLs, a significant and dose-dependent reduction of T-cell proliferation,
      ranging from 60% +/- 5% to 98% +/- 1%, was evident. Similarly, addition of BMSCs
      to T cells stimulated by polyclonal activators resulted in a 65% +/- 5% (P
      =.0001) suppression of proliferation. BMSC- induced T-cell suppression was still
      evident when BMSCs were added in culture as late as 5 days after starting of
      MLRs. BMSC-inhibited T lymphocytes were not apoptotic and efficiently
      proliferated on restimulation. BMSCs significantly suppressed both CD4(+) and
      CD8(+) T cells (65% +/- 5%, [P =.0005] and 75% +/- 15% [P =.0005], respectively).
      Transwell experiments, in which cell-cell contact between BMSCs and effector
      cells was prevented, resulted in a significant inhibition of T-lymphocyte
      proliferation, suggesting that soluble factors were involved in this phenomenon.
      By using neutralizing monoclonal antibodies, transforming growth factor beta1 and
      hepatocyte growth factor were identified as the mediators of BMSC effects. In
      conclusion, our data demonstrate that (1) autologous or allogeneic BMSCs strongly
      suppress T-lymphocyte proliferation, (2) this phenomenon that is triggered by
      both cellular as well as nonspecific mitogenic stimuli has no immunologic
      restriction, and (3) T-cell inhibition is not due to induction of apoptosis and
      is likely due to the production of soluble factors.

PMID- 11986245
TI  - Herpes simplex virus type 2-specific CD8 cytotoxic T lymphocyte cross-reactivity
      against prevalent HLA class I alleles.
AB  - Clonally expressed T-cell receptor alphabeta heterodimers are able to bind many
      different major histocompatibility complex/peptide combinations. This promiscuity
      is thought to be required for adequate surveillance against microbial and
      malignancy-associated antigens. After transplantation, T cells may react with
      nonself structures, contributing to graft-versus-host disease, in the case of
      hematopoietic stem cell transplantation, or graft failure, when the host immune
      system is preserved. We describe 2 distinct HLA A*0201-restricted, cytotoxic CD8
      T-cell responses to the prevalent chronic pathogen, herpes simplex virus type 2,
      that cross-react with cells bearing specific alleles of the common HLA B44
      family. Transfection of human or primate renal epithelial cells with HLA class I
      complementary DNA confirmed these results. Given the prevalence of this viral
      infection and the HLA alleles involved, it is possible that this cross-reactivity
      may be involved in clinically significant events.

PMID- 11986246
TI  - Unlike AML1, CBFbeta gene is not deregulated by point mutations in acute myeloid
      leukemia and in myelodysplastic syndromes.
AB  - The core-binding factor (CBF) complex is a heterodimeric transcription factor
      composed of 2 subunits, CBFalpha and CBFbeta, that play a major role in
      hematopoiesis. Both members of the CBF complex are frequently altered in acute
      myeloid leukemia (AML) by translocation, most commonly t(8;21), t(12;21), and
      t(3;21) for CBFalpha, located in 21q22, and inv(16)(p13;q22) for CBFbeta, located
      on 16q22. Recently, a new mechanism of alteration of CBFalpha, by point mutation,
      has been reported in myeloid malignancies, particularly in M0 AML. In the present
      study, we found no point mutation of the CBFbeta gene in 30 myelodysplastic
      syndromes and 100 AMLs, suggesting a limited role, if any, of CBFbeta point
      mutations in those disorders.

PMID- 11986247
TI  - Paradoxical secondary polycythemia in von Hippel-Lindau patients treated with
      anti-vascular endothelial growth factor receptor therapy.
AB  - Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer
      syndrome caused by germline mutations in the VHL tumor-suppressor gene. Central
      nervous system (CNS) and retinal hemangioblastomas are highly vascular tumors
      that are hallmarks of the disease. These tumors overexpress vascular endothelial
      growth factor (VEGF) and represent a potential target for anti-angiogenic drugs.
      We observed, after 3 to 4 months of treatment, secondary paradoxical polycythemia
      in 3 VHL patients with CNS or retinal hemangioblastomas treated by the anti-VEGF
      receptor SU5416. Hematocrit was normal before the beginning of the trial, and no
      progression of hemangioblastomas was observed. Polycythemia vera and all known
      causes of secondary polycythemia were also ruled out. Polycythemia has never been
      reported in current SU5416 trials for advanced malignancies and could express a
      specific action on red blood cell precursors occurring only in the absence of a
      functional VHL gene. These findings could also affect the inclusion of VHL
      patients with pre-existing polycythemia in future anti-VEGF receptor trials.

PMID- 11986248
TI  - Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia.
AB  - In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were
      treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held
      in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia,
      6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema,
      3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in
      whom retreatment at a reduced dose was possible, 11 patients (48%) were able to
      continue treatment beyond 3 months. None of the patients experienced a response
      in anemia, and only 2 had partial responses in splenomegaly. A greater than 50%
      increase in platelet count was documented in 11 (48%) patients, but not in those
      with baseline platelet counts of less than 100 x 10(9)/L. In vitro, imatinib
      mesylate caused variable degrees of growth suppression of myeloid and erythroid
      progenitors that unfortunately did not translate into clinical benefit.

PMID- 11986249
TI  - NUP98 is fused to the NSD3 gene in acute myeloid leukemia associated with
      t(8;11)(p11.2;p15).
AB  - Fusion between the NUP98 and NSD3 genes in a patient with acute myeloid leukemia
      associated with t(8;11)(p11.2;p15), is reported for the first time. The
      t(8;11)(p11.2;p15) was identified by classical cytogenetics. Fluorescence in situ
      hybridization (FISH) analysis revealed a split signal with a mix of BAC 118H17
      and 290A12, indicating the translocation disrupted NUP98. FISH restriction at
      8p11-12 showed a split of BAC 350N15. Molecular investigations into candidate
      genes in this BAC showed the NUP98 fusion partner at 8p11.2 was the NSD3 gene. To
      date the NSD3 gene has never been implicated in hematologic malignancies.

PMID- 11986250
TI  - Imatinib mesylate (STI571) in the treatment of relapse of chronic myeloid
      leukemia after allogeneic stem cell transplantation.
AB  - Donor lymphocyte infusion (DLI) can restore durable molecular remission in a high
      percentage of patients with chronic myeloid leukemia (CML) who have relapses
      after allogeneic stem cell transplantation, but for patients who do not respond
      survival is poor. Imatinib mesylate (STI571) is a specific inhibitor of BCR-ABL
      tyrosine kinase that can induce hematologic and cytogenetic remissions in
      patients with CML. We report here a male patient who had a relapse to chronic
      phase after stem cell transplantation for CML, did not benefit from treatment
      with DLI, and then was administered STI571 at a dose of 400 mg daily. There was a
      rapid, complete hematologic response, and complete restoration of donor-type
      hematopoiesis (100% 46, XX marrow metaphases) was achieved after 6 months of
      therapy, though RT-PCR studies still detected BCR-ABL transcripts in the blood at
      low level. This case demonstrates that imatinib mesylate can be highly effective
      in the management of patients who have relapses after allograft for CML.

PMID- 11986251
TI  - Aotus New World monkeys: model for studying malaria-induced anemia.
AB  - Falciparum malaria is a major cause of disease and death in African children and
      pregnant women, primarily due to severe anemia. We studied anemia in vaccinated
      Aotus monkeys during a second infection where the animals were considered to be
      semi-immune. Most animals had extremely low or undetectable levels of
      parasitemia; in some, anemia did not develop and reticulocytemia remained
      unchanged; in others, moderate to severe anemia developed with inappropriately
      low reticulocytemia indicating bone marrow dysfunction. Bone marrow rapidly
      responded after parasite clearance. The rapid drop in hematocrit despite
      extremely low to undetectable parasitemia indicated massive removal of uninfected
      red blood cells from the circulation that, in the presence of bone marrow
      dysfunction, led to severe anemia-the problem that occurs in African children. We
      demonstrate that Aotus monkeys are a nonhuman primate model to gain insight into
      the pathogenesis of severe anemia in African children.

PMID- 11986252
TI  - Host background immunity and human immunodeficiency virus protective vaccines, a
      major consideration for vaccine efficacy in Africa and in developing countries.

PMID- 11986253
TI  - PCR in diagnosis of infection: detection of bacteria in cerebrospinal fluids.

PMID- 11986255
TI  - Comparison of human immunodeficiency virus antigens as stimulants for lymphocyte
      proliferation assays.
AB  - CD4 proliferative responses to the human immunodeficiency virus (HIV) type 1 (HIV
      1) p24 (gag) antigen inversely correlate with the plasma viral load in HIV
      infected subjects who control viral replication without antiretroviral therapy.
      Use of a single HIV-1 protein to assess CD4 proliferative responses may not
      reflect the global response to this pathogen. We compared the abilities of HIV
      p24 and gp120 antigens from two different vendors, an inactivated whole HIV-1 MN
      virion preparation and an HIV-1E culture supernatant antigen, to elicit
      proliferative responses in HIV-seropositive and HIV-seronegative donors.
      Peripheral blood mononuclear cells from 12 HIV-seropositive donors (each with HIV
      1 loads <4,000 copies/ml of plasma, >350 CD4 T lymphocytes/mm(3), and no
      antiretroviral therapy) and 15 HIV-seronegative donors were assessed with
      multiple concentrations of each stimulant by standard lymphocyte proliferation
      assays. Wide variations in response rates were found, with zero, three, five, and
      eight individuals demonstrating stimulation indices of >3 for the HIV culture
      antigen supernatant, gp120, p24, and inactivated whole-virus preparations,
      respectively. These results suggest that the use of the inactivated whole virus
      resulted in a more sensitive assay for detection of CD4 T-lymphocyte function in
      HIV-infected subjects.

PMID- 11986254
TI  - In vitro and animal models of human immunodeficiency virus infection of the
      central nervous system.

PMID- 11986256
TI  - Endotoxin-induced gamma interferon production: contributing cell types and key
      regulatory factors.
AB  - Gamma interferon (IFN-gamma) is an important mediator of endotoxin
      (lipopolysaccharide [LPS])-induced immune responses. However, the specific cell
      types that produce IFN-gamma in response to LPS and the cellular factors that
      regulate LPS-induced IFN-gamma production have not been fully determined. The
      present studies were undertaken to characterize the cell populations that produce
      IFN-gamma after LPS challenge in the spleens of mice and to determine the
      regulatory factors that modulate LPS-induced production of IFN-gamma. Our studies
      show that the levels of splenic IFN-gamma mRNA and protein production peak at 6
      and 8 h, respectively, after systemic LPS challenge. Approximately 60% of IFN
      gamma-producing cells are natural killer (NK) cells (CD3(-)DX5(+)) and 25% are
      NKT cells (CD3(+)DX5(+)). Most of the remaining IFN-gamma-producing cells are T
      cells (CD3(+)DX5(-)), macrophages, and dendritic cells. Functionally, interleukin
      12 (IL-12) is the major IFN-gamma-stimulating factor after LPS challenge, with
      costimulation provided by IL-15, IL-18, and B7 proteins. IL-10 is a major
      inhibitor of LPS-induced IFN-gamma production. Unlike intact heat-killed gram
      negative and gram-positive bacteria, the class II major histocompatibility
      complex did not play a functional role in LPS-induced IFN-gamma production. LPS
      is a potent stimulus for splenic IL-10, IL-12 p40, and IL-15 mRNA expression,
      whereas IL-12 p35 and IL-18 mRNAs, as well as B7 proteins, are constitutively
      expressed in the mouse spleen. Of the factors studied, IL-18 serves as the most
      potent costimulus with IL-12 for IFN-gamma production, followed by IL-15 and B7
      proteins. These data demonstrate that NK cells and NKT cells are the most
      abundant IFN-gamma-producing cells in the mouse spleen after LPS challenge and
      that IL-10 and IL-12 are key functional regulators of LPS-induced IFN-gamma
      production.

PMID- 11986257
TI  - Use of immunoglobulin m cross-reactions in differential diagnosis of human
      flaviviral encephalitis infections in the United States.
AB  - To define the virus specificity of the immunoglobulin M (IgM) antibody-capture
      enzyme-linked immunosorbent assay (MAC-ELISA) among the medically important
      members of the Japanese encephalitis (JE) virus serocomplex of flaviviruses, 103
      IgM-positive human serum samples from patients with confirmed West Nile (WN)
      virus, St. Louis encephalitis (SLE) virus, or JE virus infections were assembled
      and simultaneously tested against all three viral antigens in a standardized MAC
      ELISA. Of the serum samples tested, 96 (93%) showed higher positive-to-negative
      absorbance ratios (P/Ns) with the infecting virus antigen compared to those
      obtained with the other two virus antigens. Of the seven specimens with higher
      P/Ns with heterologous virus antigens, six were from patients with SLE virus
      infections (the serum samples had higher levels of reactivity with WN virus
      antigen) and one was from a patient with a JE virus infection (this serum sample
      also had a higher level of reactivity with WN virus antigen). Not surprisingly,
      similar virus specificity was observed with WN virus-elicited IgM in
      cerebrospinal fluid. As shown in previous studies, a subset of these specimens
      was even less reactive in the MAC-ELISA with dengue virus, a member of a
      different flavivirus serocomplex. The degree of virus cross-reactivity did not
      appear to be related to days postonset, at least during the first 40 days of
      infection. Infections with WN virus could be correctly distinguished from
      infections with SLE virus on the basis of the observed anti-viral IgM cross
      reactivities alone 92% of the time. Infections with SLE virus resulted in
      antibody that was more cross-reactive, so identification of SLE virus as the
      infecting agent by use of MAC-ELISA cross-reactivity alone was more problematic.

PMID- 11986258
TI  - CD8 alpha-deficient mice are highly susceptible to 5-fluorouracil-induced
      lethality.
AB  - Intestinal intraepithelial lymphocytes (i-IEL) expressing CD8 alpha are located
      in the intestine and may confer protection against invasion of intestinal
      microflora. We found that mice rendered deficient in CD8 alpha molecules by
      homologous recombination were susceptible to 5-fluorouracil (5-FU)-induced
      lethality accompanied by translocation of members of the enterobacteria. The
      number of i-IEL was greatly reduced on day 6 after 5-FU administration in both
      CD8 alpha(+/-) mice and CD8 alpha(-/-) mice, whereas the recovery of the level of
      i-IEL thereafter was significantly impaired in CD8 alpha(-/-) mice compared with
      that in CD8 alpha(+/-) mice. The ability of i-IEL to produce gamma interferon in
      response to immobilized T-cell receptor (TCR) alpha beta or TCR gamma delta
      monoclonal antibodies was significantly lower in CD8 alpha(-/-) mice than in CD8
      alpha(+/-) mice. Transfer of CD8(+) i-IEL conferred significant protection
      against 5-FU-induced lethality in CD8 alpha(-/-) mice. The results suggest that
      CD8(+) i-IEL play an important role in protection against 5-FU-induced lethality
      with translocation of Enterobacteriaceae.

PMID- 11986259
TI  - Levels of soluble CD40 ligand (CD154) in serum are increased in human
      immunodeficiency virus type 1-infected patients and correlate with CD4(+) T-cell
      counts.
AB  - CD40 ligand (CD40L or CD154) is a costimulatory molecule expressed mainly on
      activated CD4(+) T cells. Concentrations of the soluble form of CD40L (sCD40L) in
      serum were determined for a cohort of 77 human immunodeficiency virus type 1 (HIV
      1)-infected patients before and after initiation of highly active antiretroviral
      treatment (HAART) by a quantitative enzyme-linked immunosorbent assay.
      Circulating sCD40L levels were higher by twofold in untreated patients than in
      healthy controls (means +/- standard deviations [SD]: 1.41 +/- 1.48 versus 0.69
      +/- 0.59 ng/ml; P < 0.001). HIV-1-infected patients classified as CD4 T-cell
      category 1 had significantly higher sCD40L levels than patients classified as CD4
      categories 2 and 3 (mean +/- SD: 2.08 +/- 1.46 ng/ml versus 1.57 +/- 1.58
      [category 2] and 0.94 +/- 1.25 ng/ml [category 3]; P = 0.046), while no
      correlation with clinical categories A, B, and C was found. Individual serum
      sCD40L levels correlated with CD4(+) T-cell counts (P = 0.039) but not with viral
      load, gamma globulin levels, or acute-inflammatory-response markers. After 8 to
      12 months of HAART, a further threefold increase of serum sCD40L levels, which
      paralleled the increase of CD4(+) T-cell counts, was observed. These novel
      findings suggest that sCD40L measurement in HIV-1-infected patients could serve
      as a new surrogate marker useful in the assessment of treatment efficacy,
      especially in settings where well-equipped laboratories and funding required for
      CD4(+) T-cell count and viral load measurements are not available.

PMID- 11986260
TI  - Inclusion fluorescent-antibody test as a screening assay for detection of
      antibodies to Chlamydia pneumoniae.
AB  - A study was conducted to determine the ability of the inclusion
      immunofluorescence assay (inclusion IFA) to act as a screening test to detect
      samples with antibodies to Chlamydia pneumoniae; microimmunofluorescence (MIF)
      was used as the "gold standard." In addition, the inclusion IFA was compared
      using HEp-2 cells infected with either C. pneumoniae CM-1 or Chlamydia
      trachomatis serovar E. A total of 331 serum samples representing a range of MIF
      titers were evaluated. The sensitivities of the inclusion IFA for detecting
      samples with C. pneumoniae MIF titers of > or = 16 were 96.9 and 74.8% with C.
      pneumoniae- and C. trachomatis-infected cells, respectively. For samples with an
      elevated C. pneumoniae MIF titer of > or = 512, the sensitivities of the C.
      pneumoniae- and C. trachomatis-based inclusion IFA were 97.0 and 8.8%,
      respectively. These results suggest that the inclusion IFA is not a genus
      specific test, as evidenced by the failure of the C. trachomatis-infected cells
      to detect a significant number of samples with C. pneumoniae antibodies. Samples
      that had elevated C. pneumoniae inclusion IFA and MIF titers but that were found
      negative (titer, <16) by the C. trachomatis inclusion IFA were further tested by
      an in vitro neutralization assay for functional antibodies that might not have
      been detected by the serological assays. The in vitro neutralization results
      corroborated the serological results in that all seven sera tested had a
      neutralization titer for C. pneumoniae (range, 20 to 225), while all but one
      failed to have any effect on the infectivity of C. trachomatis serovar E. While
      the C. pneumoniae inclusion IFA had a high sensitivity for detecting chlamydial
      antibodies, depending on whether it was used as a screening test for detecting
      samples with low (> or = 16) or elevated (> or = 512) MIF titers, its specificity
      ranged from 53.4 to 77.1%. In conclusion, the inclusion IFA with C. pneumoniae
      infected cells was best suited as a sensitive screening test for identifying
      specimens with elevated MIF titers (those associated with a possible acute
      infection with C. pneumoniae).

PMID- 11986261
TI  - Predicting kala-azar disease manifestations in asymptomatic patients with latent
      Leishmania donovani infection by detection of antibody against recombinant K39
      antigen.
AB  - Clinically visceral leishmaniasis is suspected in only a fraction of infected
      persons, as the majority of these may not have clinical manifestations and remain
      asymptomatic. There is scanty information on diagnosing latent infections and
      predicting disease in asymptomatic persons. We therefore carried out a study on
      asymptomatic contacts of patients with visceral leishmaniasis and post-kala-azar
      dermal leishmaniasis by using methods for detection of antibody to recombinant
      K39 (rK39) antigen. A total of 240 patients with leishmaniasis and 150
      asymptomatic contacts were tested for anti-rK39 immunoglobulin G (IgG) and IgA
      antibodies. Fifty-five asymptomatic persons were found to be seropositive. These
      individuals were monitored every 3 months for 1 year. On follow-up, 43.9% of the
      asymptomatic seropositive contacts developed kala-azar within the first 3 months,
      and a cumulative total of 69% developed kala-azar within 1 year. The rest
      remained asymptomatic and self-healed the infection. The sensitivity and
      specificity of rK39 enzyme-linked immunosorbent assay (ELISA) and dipstick tests
      were 100%, while an in-house-developed latex agglutination test had 80%
      sensitivity. The antibody profile showed that the IgG anti-rK39 antibodies
      reached a titer of up to 10(-6) within 6 months of infection, started declining
      thereafter, and completely disappeared in 2 to 3 years in successfully treated
      cases. Significant titers of IgA antibodies were detectable a little earlier than
      those of IgG antibodies and were undetectable after 6 months. The study showed
      that mass screening of family members and contacts by using anti-rK39 ELISA could
      be a highly reliable tool for early diagnosis and to plan prophylactic treatment
      of latently infected asymptomatic carriers to eradicate kala-azar.

PMID- 11986262
TI  - Usefulness of hydatid cyst fluid of Echinococcus granulosus developed in mice
      with secondary infection for serodiagnosis of cystic Echinococcosis in humans.
AB  - The aim of this work was to assess the usefulness of hydatid cyst fluid (HCF) of
      Echinococcus granulosus, obtained from mice experimentally infected with hydatid
      cyst tissue homogenates, for the serodiagnosis of cystic echinococcosis (CE) in
      humans. The sensitivity and specificity of HCF obtained from mice for the
      detection of immunoglobulin G (IgG) antibodies in the sera of CE patients were
      compared with those of HCF from sheep and/or from a human CE patient by using
      immunoblotting (IB) and an enzyme-linked immunosorbent assay (ELISA). HCFs
      obtained from three different host species all were highly useful for
      immunoblotting, and sera from 19 (95%) of 20 CE patients equally recognized the
      antigen B subunit (approximately 8 kDa). HCF from mice showed a cross-reaction
      with 9 of 20 alveolar echinococcosis (AE) sera (45%), whereas HCFs from two other
      host species cross-reacted with 14 of the AE sera (70%). Although 2 (10%) of 20
      sera from neurocysticercosis (NCC) patients were false positive with HCF from
      both sheep and humans, none of these sera showed a positive reaction with HCF
      from mouse origin. ELISAs with HCFs from both mouse and sheep origins detected
      all 20 CE and AE sera; however, these ELISAs showed 45% (9 of 20) and 60% (12 of
      20) false-positive reactions with 20 NCC sera, respectively. The presence of
      nonspecific human IgG in HCF obtained from a CE patient prevented us from
      applying it to the ELISA. HCF of E. granulosus, obtained from laboratory mice
      with a secondary infection with hydatid cyst tissue homogenates, appears to be
      highly useful for the serodiagnosis of CE in humans and may be useful in domestic
      animals.

PMID- 11986263
TI  - Optimization of a human papillomavirus-specific enzyme-linked immunosorbent
      assay.
AB  - A strategy was developed for the control, standardization, and critical
      evaluation of an enzyme-linked immunosorbent assay (ELISA) for the detection of
      human papillomavirus-specific immunoglobulin G in human sera. Control human sera,
      polyclonal animal sera, and monoclonal antibodies were used to establish optimal
      assay parameters, including antigen coating, serum dilutions, and criteria for
      daily reproducibility, monitoring, and rejection of assays. Three evaluation
      techniques were used in parallel to define an optimal cutoff absorbance value
      that yields greater than 93% sensitivity and 98.5% specificity in the assay's
      ability to discriminate positive and negative control sera. This strategy
      provides an optimal method by which to determine cutoff absorbance values for
      ELISA.

PMID- 11986264
TI  - Treatment with megestrol acetate improves human immunodeficiency virus-associated
      immune thrombocytopenia.
AB  - Splenic macrophage Fc gamma receptors participate in the pathophysiology of
      immune cytopenias, and in such disorders, the beneficial effects of
      glucocorticoids are in part mediated by decreased expression of macrophage Fc
      gamma receptors. In the animal model, progesterones, like glucocorticoids,
      inhibit expression of these receptors. Megestrol acetate (MA) is a progesterone
      frequently used for treating human immunodeficiency virus (HIV)-associated
      anorexia-cachexia. Twenty-eight patients with HIV-associated thrombocytopenia
      with shortened platelet survival and increased platelet-associated immunoglobulin
      G (IgG) who were being treated with MA for anorexia-cachexia were prospectively
      studied for a 6-month period to assess the potential role of progesterones in the
      treatment of immune thrombocytopenia. Treatment with MA for non-consecutive
      periods of 2 months and 1 month significantly increased platelet count and
      platelet survival without significant alteration of platelet-associated
      immunoglobulin levels. Of the 28 patients studied, 22 presented a complete
      response, 19 presented a complete response 1 month after finishing the MA
      treatment regimen, and 12 remained in complete response for a further month.
      Expression of Fc gamma receptors (Fc gamma RI and Fc gamma RII) by peripheral
      blood monocytes and the in vitro recognition of IgG-sensitized cells by monocytes
      were significantly decreased by the MA treatment. Decreased expression and
      functioning of these receptors significantly correlated with platelet counts and
      survival times, but no relationship was found with platelet-associated
      immunoglobulin, circulating immune complexes, body mass index, plasma HIV load,
      or CD4 lymphocyte levels. These results suggest that treatment with
      progesterones, like MA, may be an alternative therapy for immune cytopenias, with
      few side effects.

PMID- 11986265
TI  - Evaluation of the in vitro pyrogen test system based on proinflammatory cytokine
      release from human monocytes: comparison with a human whole blood culture test
      system and with the rabbit pyrogen test.
AB  - The reliability of an in vitro pyrogen test system based on proinflammatory
      cytokine release from human monocytic cells was assessed by comparison with a
      test system based on a human whole blood culture as well as with the conventional
      rabbit pyrogen test. The human cells used as the pyrogen indicator cells were
      newly selected by subcloning of a human monocytic cell line, Mono-Mac-6. The
      selected cells, named MM6-CA8, responded to various pyrogens, including
      endotoxin, peptidoglycan (PG), Staphylococcus aureus Cowan 1 (SAC), and poly(I x
      C), with a high sensitivity and produced proinflammatory cytokines, such as
      interleukin 1 (IL-1), IL-6, and tumor necrosis factor alpha. Among these
      cytokines, IL-6 was produced most sensitively in response to traces of the
      pyrogens and detected in the largest quantities in the culture medium. The
      cytokine-producing responses of MM6-CA8 cells correlated significantly with the
      responses of cultured human whole blood, which represents an ex vivo culture test
      system reproducing pyrogen-induced cytokine production in the human body. In
      terms of cytokine inducibility, the pyrogens were ranked in the order endotoxin >
      PG > poly (I. C) > SAC in both culture systems, a ranking which almost agreed
      with the ranking of their pyrogenicity as assessed by the rabbit pyrogen test.
      These results suggest that the in vitro responsiveness of MM6-CA8 cells to
      various pyrogens is highly relevant for human pyrogenic reactions. Therefore, the
      in vitro test system is useful and reliable for detecting the presence of
      materials that are pyrogenic for humans.

PMID- 11986266
TI  - YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis.
AB  - YKL-40, a member of the family 18 glycosyl hydrolases, is secreted by activated
      neutrophils and macrophages. It is a growth factor for connective tissue cells
      and a potent migration factor for endothelial cells and may function in
      inflammation and tissue remodeling. YKL-40 was determined in 134 cerebrospinal
      fluid (CSF) samples taken on admission from patients suspected of having
      meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with
      encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were
      significantly higher in patients with purulent meningitis (median, 663
      microg/liter [range, 20 to 8,960]) and encephalitis (5,430 microg/liter [620 to
      11,600]) than in patients with lymphocytic meningitis (137 microg/liter [41 to
      1,865]) or patients without meningitis (167 microg/liter [24 to 630]) (Kruskal
      Wallis and Dunn multiple comparison tests, P < 0.001). CSF YKL-40 levels were
      also determined for 26 patients with purulent meningitis having a repuncture, and
      patients who died (n = 5) had significantly higher YKL-40 levels than patients
      who survived (n = 21) (2,100 microg/liter [1,160 to 7,050] versus 885
      microg/liter [192 to 15,400], respectively; Mann-Whitney test, P = 0.018). YKL-40
      was most likely locally produced, since patients with infections of the central
      nervous system had CSF YKL-40 levels that were at least 10-fold higher than the
      corresponding levels in serum (2,033 microg/liter [470 to 11,600] versus 80
      microg/liter [19 to 195]). The CSF neopterin level was the biochemical parameter
      in CSF and blood that correlated best with CSF YKL-40 levels, indicating that YKL
      40 may be produced by activated macrophages within the central nervous system. In
      conclusion, high levels of YKL-40 in CSF are found in patients with purulent
      meningitis.

PMID- 11986267
TI  - Reduced levels of nitric oxide metabolites in cerebrospinal fluid are associated
      with equine protozoal myeloencephalitis.
AB  - Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily
      associated with infection with the apicomplexan Sarcocystis neurona. Infection
      with this parasite alone is not sufficient to induce the disease, and the
      mechanism of neuropathogenesis associated with EPM has not been reported. Nitric
      oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector
      and is produced in response to several parasitic protozoa. The purpose of this
      work was to determine if the concentration of NO metabolites (NO(x)(-)) in the
      cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NO(x)(-)
      levels were measured before and after transport-stressed, acclimated, or
      dexamethasone-treated horses (n = 3 per group) were experimentally infected with
      S. neurona sporocysts. CSF NO(x)(-) levels were also compared between horses that
      were diagnosed with EPM after natural infection with S. neurona and horses that
      did not have clinical signs of disease or that showed no evidence of infection
      with the parasite (n = 105). Among the experimentally infected animals, the mean
      CSF NO(x)(-) levels of the transport-stressed group, which had the most severe
      clinical signs, was reduced after infection, while these values were found to
      increase after infection in the remaining groups that had less severe signs of
      EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF
      NO(x)(-) concentration than clinically normal horses with antibodies (Abs)
      against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had
      a significantly lower mean CSF NO(x)(-) concentration than horses that did not
      have neurologic signs (n = 24). In conclusion, lower CSF NO(x)(-) levels were
      associated with clinical EPM, suggesting that measurement of CSF NO(x)(-) levels
      could improve the accuracy of diagnostic tests that are based upon detection of
      S. neurona-specific Abs in CSF alone and that reduced NO levels could be causally
      related to the development of EPM.

PMID- 11986268
TI  - Sensitive and specific identification of Neospora caninum infection of cattle
      based on detection of serum antibodies to recombinant Ncp29.
AB  - Neosporosis is an economically important disease of dairy cattle caused by the
      protozoan Neospora caninum. Diagnostic tests for neosporosis are complicated by
      the potential for cross-reaction of antibodies to antigens that are similar
      between N. caninum and closely related parasites Toxoplasma gondii and
      Sarcocystis cruzi. To provide a sensitive and specific assay for detecting
      antibodies to N. caninum in the serum of infected animals, we have investigated a
      recombinant form of the antigen known as Ncp29 (rNcp29), which is a major surface
      protein of the parasite. Ncp29 is encoded by a gene that is homologous to the
      SAG1 gene previously characterized from T. gondii. An enzyme-linked immunosorbent
      assay (ELISA) was used to screen animals for the presence of serum antibodies
      specific to rNcp29. The rNcp29 ELISA readily distinguished between cattle known
      to be infected with N. caninum (optical density [OD] > 1.2 at 1:500 or greater
      dilution) and negative controls (OD < 0.5 at 1:500). Additionally, sera from
      animals that were infected with T. gondii or S. cruzi were negative. The rNcp29
      ELISA developed here provides a specific and sensitive assay for detecting
      neosporosis in cattle.

PMID- 11986269
TI  - Vitamin A levels and immunity in humans.
AB  - In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to
      type 1 (cellular) cytokines; there are no similar data for humans. Control of
      human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections
      requires type 1 cytokine (cellular) immunity. These infections and vitamin A
      deficiency are highly prevalent in Africa. We therefore examined the interactions
      among serum vitamin A levels, immune parameters, HIV infection status,
      Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine
      profile), and clinical findings for 70 hospitalized children in Malawi, Africa.
      Directly conjugated monoclonal antibodies and flow cytometry were used to assess
      cell-specific cytokine production by peripheral blood monocytes and lymphocyte
      subpopulations. The statistical techniques employed included nonparametric
      statistics and logistic regression analyses. Thirty percent of the participants
      had severe vitamin A deficiency (<10 microg/dl), 34% had moderate deficiency (10
      to <20 microg/dl), and 36% had normal levels (> or = 20 microg/dl). Vitamin A
      levels were lower for HIV-positive than for HIV-negative children (median, 10 and
      17 microg/dl, respectively). Vitamin A-deficient children (<20 microg/dl) were
      more likely than non-vitamin A-deficient children to have higher proportions of
      natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios
      of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing
      monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A
      deficient children were also more likely than non-vitamin A-deficient children to
      exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83%
      versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A
      status did not vary with gender, age, incidence of malaria parasitemia, blood
      culture positivity, or rates of mortality (6% of vitamin A-deficient children
      died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were
      associated with a relative type 1 cytokine dominance and proportionately more NK
      cells, both of which may be somewhat beneficial to persons who are exposed to
      HIV, M. tuberculosis, or other type 1 pathogens.

PMID- 11986270
TI  - Impact of hepatitis B and hepatitis C virus infections in a hematology-oncology
      unit at a children's hospital in Nicaragua, 1997 to 1999.
AB  - The risk of acquiring both hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections in patients with hematological-oncological disorders has been
      documented. However, the impact and risk factors for such infections from
      different geographical areas vary, and the use of both immunological and
      molecular assays to determine HCV infections has been our approach. Children from
      a hematology-oncology unit (HOU) in Nicaragua were studied for both HBV and HCV
      serological markers; studies for the latter used both immunological (anti-HCV)
      and molecular (HCV RNA) assays. The children from the HOU included patients with
      leukemia, lymphoma, other neoplasias, and anemia and a smaller group with other
      hematological diseases. As a control group, children from other units at the same
      hospital were enrolled, as well as health care workers attending both patient
      populations. Pertinent clinical and personal data for each child at the HOU were
      obtained for statistical analysis. Of the 625 children from the HOU enrolled in
      this study 53.3% were infected with HCV and 29.4% had a prior or present HBV
      infection. In the child patient control group 3.2% had HBV markers and all were
      negative for HCV. The group of children with leukemia had the highest infection
      rate for both HBV and HCV. However, the determination of anti-HCV was found to
      have an overall low sensitivity in children from HOU, and a retest consisting of
      a molecular assay to determine HCV RNA was performed to better establish the
      total number of HCV-infected subjects in this group. The highest independent risk
      factor for infection was hospitalization. The very high prevalence rates for both
      HBV and HCV infection in this patient group indicate an urgent need to implement
      better control of known risk factors and to consider the use of both
      immunological and molecular assays for HCV diagnostic purposes.

PMID- 11986271
TI  - Cloning and expression of a Helicobacter bilis immunoreactive protein.
AB  - In an effort to identify immunoreactive Helicobacter bilis antigens with
      potential for serodiagnosis, sera from mice experimentally infected with H. bilis
      were used to screen an H. bilis genomic DNA expression library. Among 17
      immunoreactive clones, several contained sequences that encoded a predicted 167
      kDa protein (P167). Five overlapping P167 peptides (P167A to P167E) of
      approximately 40 kDa each were generated and tested. Immune sera reacted with
      fragments P167C and P167D at dilutions of 1:1,600 and 1:6,400, respectively, and
      reacted with an H. bilis membrane extract at a dilution of 1:800 in an enzyme
      linked immunosorbent assay. Sera from mice experimentally infected with H.
      hepaticus did not react with P167C and P167D. Sera from mice naturally infected
      with H. bilis but not sera from mice naturally infected with H. hepaticus reacted
      with P167C and P167D. Hyperimmune sera against P167C peptide reacted with
      recombinant P167C and with a 120-kDa band in H. bilis lysates but did not react
      with a protein of the same size on immunoblots prepared from H. hepaticus, H.
      muridarum, or unrelated Borrelia burgdorferi and Campylobacter jejuni whole-cell
      lysates. Nevertheless, the P167A, P167B, P167C, and P167D primers, but not the
      P167E primers, amplified DNA from H. hepaticus, and all five primer sets
      amplified DNA from H. muridarum. These results suggest that P167 is an
      immunodominant, H. bilis-specific antigen that may have potential for use in
      serodiagnosis.

PMID- 11986272
TI  - Multiplex assay for detection of strain-specific antibodies against the two
      variable regions of the G protein of respiratory syncytial virus.
AB  - The role of strain differences in respiratory syncytial virus (RSV) disease has
      not been clearly defined. To investigate the possibility that strain differences
      contribute to susceptibility to repeat infections, we developed assays to detect
      antibodies to the two variable regions of the RSV G protein by cloning and
      expressing the internal variable region at amino acids (aa) 60 to 172 (g1) and
      the carboxy-terminal variable region at aa 193 to the carboxy terminus (g2) from
      different genotypes of RSV. The purified proteins were covalently linked to beads
      with different proportions of red and orange fluorescent dyes and reacted against
      serum specimens. Antibody reacting against the differently colored beads, and
      thus against different G polypeptides, was detected by use of flow cytometry and
      the Luminex system. This assay system detected group- and, to some extent,
      genotype-specific responses to RSV infection and can be used to investigate the
      role of strain differences in RSV disease.

PMID- 11986273
TI  - Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay.
AB  - We developed a quantitative enzyme immunoassay (EIA) for antibody to hepatitis E
      virus (HEV) by using truncated HEV capsid protein expressed in the baculovirus
      system to improve seroepidemiology, to contribute to hepatitis E diagnosis, and
      to enable vaccine evaluations. Five antigen lots were characterized; we used a
      reference antiserum to standardize antigen potency. We defined Walter Reed
      antibody units (WR U) with a reference antiserum by using the four-parameter
      logistic model, established other reference pools as assay standards, and
      determined the conversion factor: 1 WR U/ml = 0.125 World Health Organization
      unit (WHO U) per ml. The EIA performed consistently; median intra- and inter-test
      coefficients of variation were 9 and 12%, respectively. The accurate minimum
      detection limit with serum diluted 1:1,000 was 5.6 WR U/ml; the test could detect
      reliably a fourfold antibody change. In six people followed from health to onset
      of hepatitis E, the geometric mean antibody level rose from 7.1 WR U/ml to
      1,924.6 WR U/ml. We used the presence of 56- and 180-kDa bands by Western
      blotting as a confirmatory test and to define true-negative and -positive serum
      specimens. A receiver-operating characteristics plot identified 30 WR U/ml as an
      optimum cut-point (sensitivity, 86%; specificity, 89%). The EIA detected antibody
      more sensitively than a commercially available test. The EIA was transferred to
      another laboratory, where four operators matched reference laboratory results for
      a panel of unknowns. Quantitation of antibody to HEV and confirmation of its
      specificity by Western blotting make HEV serology more meaningful.

PMID- 11986274
TI  - Activation of human NK cells by staphylococci and lactobacilli requires cell
      contact-dependent costimulation by autologous monocytes.
AB  - NK cells are instrumental in innate immune responses, in particular for the early
      production of gamma interferon (IFN-gamma) and other cytokines necessary to
      control certain bacterial, parasitic, and viral infections. NK cell-mediated
      effector functions are controlled by a fine balance between distinct receptors
      mediating activating and inhibitory signals; however, little is known about
      activating receptors on NK cells and their corresponding ligands. Several studies
      have shown that commensal lactobacilli isolated from the human gastrointestinal
      tract activate human mononuclear cells and are potent inducers of IFN-gamma and
      monocyte-derived interleukin 12 (IL-12). NK cell activation was shown for
      Lactobacillus johnsonii La1. In this study the cellular mechanisms of in vitro NK
      cell activation by gram-positive bacteria were analyzed. Staphylococcus aureus-
      and L. johnsonii La1-mediated activation of CD3(-) CD16(+) CD56(+) human
      peripheral blood NK cells, including expression of the activation antigen CD69
      and secretion of IFN-gamma, required cell contact-dependent costimulation by
      autologous monocytes. S. aureus- and L. johnsonii-preactivated monocytes retained
      their capacity to induce NK cell activation. In contrast, cytokine-primed
      monocytes completely failed to induce NK cell activation unless bacteria were
      present. This suggests that phagocytosis of bacteria provided additional
      coactivation signals on accessory cells that may differ from those induced by
      tumor necrosis factor and IFN-gamma. Blocking of costimulatory molecules by B7.1,
      B7.2, and IL-12 but not CD14 monoclonal antibodies inhibited S. aureus- and L.
      johnsonii-induced effector function of NK cells. Our data suggest an important
      role for accessory cell-derived signals in the process of NK cell activation by
      gram-positive bacteria.

PMID- 11986275
TI  - Infection of tick cells and bovine erythrocytes with one genotype of the
      intracellular ehrlichia Anaplasma marginale excludes infection with other
      genotypes.
AB  - Anaplasma marginale, a tick-borne rickettsial pathogen of cattle, is endemic in
      several areas of the United States. Many geographic isolates of A. marginale that
      occur in the United States are characterized by the major surface protein 1a,
      which varies in sequence and molecular weight due to different numbers of tandem
      repeats of 28 or 29 amino acids. Recent studies (G. H. Palmer, F. R. Rurangirwa,
      and T. F. McElwain, J. Clin. Microbiol. 39:631-635, 2001) of an A. marginale
      infected herd of cattle in an area of endemicity demonstrated that multiple
      msp1alpha genotypes were present but that only one genotype was found per
      individual bovine. These findings suggested that infection of cattle with other
      genotypes was excluded. The present study was undertaken to confirm the
      phenomenon of infection exclusion of A. marginale genotypes in infected bovine
      erythrocytes and cultured tick cells. Two tick-transmissible isolates of A.
      marginale, one from Virginia and one from Oklahoma, were used for these studies.
      In two separate trials, cattle inoculated with equal doses of the two isolates
      developed infection with only one genotype. Tick cell cultures inoculated with
      equal doses of the two isolates became infected with only the Virginia isolate of
      A. marginale. When cultures were inoculated with different ratios of the Oklahoma
      and Virginia isolates of A. marginale, the isolate inoculated in the higher ratio
      became established and excluded infection with the other. When cultures with
      established infections of one isolate were subsequently infected with the other,
      only the established isolate was detected. We documented infection exclusion
      during initial infection in cell culture by labeling each isolate with a
      different fluorescent dye. After 2 days in culture, only a single isolate was
      detected per cell by fluorescence microscopy. Finally, when Anaplasma ovis
      infections were established in cultures that were subsequently inoculated with
      the Virginia or Oklahoma isolate of A. marginale, A. marginale infection was
      excluded. These studies confirm that infection exclusion occurs with A. marginale
      in bovine erythrocytes and tick cells, resulting in the establishment of only one
      genotype, and appears to be the first report of infection exclusion for Anaplasma
      and Ehrlichia species.

PMID- 11986276
TI  - Animal model of Mycoplasma pneumoniae infection using germfree mice.
AB  - We have attempted to establish a gnotobiotic mouse model monoassociated with
      Mycoplasma pneumoniae following single or repeated infection to examine the
      mechanism of pathogenesis following M. pneumoniae infection. M. pneumoniae
      inoculated into germfree mice colonized equally well at 10(5) CFU/lung in both
      single infection and repeated infection. In histopathological observation,
      repeatedly infected mice showed pneumonia with mild infiltration of mononuclear
      cells and macrophages. Antibody titers against M. pneumoniae rose in the
      repeatedly infected mice but not in the singly infected mice. The percentage of
      CD4-positive, CD8-positive, and CD25-positive lymphocytes infiltrated in the lung
      was increased in the repeatedly infected mice. In contrast, the lymphocyte subset
      in the spleen was not significantly different among mock-, singly, and repeatedly
      infected mice. In the study of cytokine productivity of spleen cells, production
      of interleukin (IL)-4 and IL-10 was significantly increased and that of gamma
      interferon was remarkably increased in the mice following repeated infection.
      These results indicate that a gnotobiotic mouse model monoassociated with M.
      pneumoniae was established and that immune mechanisms might be involved in the
      pathogenesis in pneumonia following M. pneumoniae infection.

PMID- 11986277
TI  - Low-dose UVB contributes to host resistance against Leishmania amazonensis
      infection in mice through induction of gamma interferon and tumor necrosis factor
      alpha cytokines.
AB  - UV radiation suppresses the immune response, a fact which raises the question of
      whether the phenomenon may find practical applications in the outcome of
      infectious diseases. In this study, BALB/c mice were exposed to low-dose UVB (250
      J/m(2)) from Dermaray M-DMR-100 for 4 consecutive days. Twelve hours after the
      last UV exposure, groups of mice were injected with 2 x 10(6) Leishmania
      amazonensis promastigotes. The development of skin lesions, as assessed by
      measurement of visible cutaneous lesions, was significantly suppressed in low
      dose UVB-irradiated mice compared to nonirradiated controls. In order to
      characterize the cytokines involved in this phenomenon, BALB/c mice were
      irradiated with identical doses of UVB, and gamma interferon (IFN-gamma), tumor
      necrosis factor alpha (TNF-alpha), and interleukin 4 cytokine levels in blood
      serum and skin were examined at different times by a sandwich enzyme-linked
      immunosorbent assay, immunohistochemical analysis, and reverse transcription (RT)
      PCR. Upregulated expression of serum IFN-gamma and TNF-alpha was observed from 6
      to 24 h. Positive results for IFN-gamma and TNF-alpha in UVB-irradiated mice were
      obtained by immunohistochemical analysis. By RT-PCR, the mRNA expression of both
      IFN-gamma and TNF-alpha cytokines was detected in a time-dependent manner only in
      UVB-irradiated mice. Histopathological analysis and electron microscopy revealed
      that cellular infiltration, tissue parasitism, and parasitophorus vacuoles in
      irradiated mice were markedly less noticeable than those in nonirradiated
      controls. These results suggested that low-dose UVB irradiation played a pathogen
      suppressing role in Leishmania-susceptible BALB/c mice via systemic and local
      upregulation of Th1 (IFN-gamma and TNF-alpha) cytokines.

PMID- 11986278
TI  - Polyclonal antibodies to glutathione S-transferase--verotoxin subunit a fusion
      proteins neutralize verotoxins.
AB  - The A1 subunits of verotoxin-1 (VT1) and VT2 genes were cloned into pGEX-4T-2 for
      the expression of glutathione S-transferase (GST) fusion proteins. The N-terminal
      and the transmembrane regions of the A1 subunits were excluded from the
      constructs in order to increase the product yields. Polyclonal anti-VT1A1 and
      anti-VT2A1 antibodies were produced by immunizing rabbits with GST-VT1A1 and GST
      VT2A1 fusion proteins, respectively. The antibodies were tested for their ability
      to neutralize active toxins from 45 VT-producing Escherichia coli (VTEC) strains.
      The antibodies had significantly high neutralizing activities against their
      homologous toxins. The average percentages of neutralization of VT1 by anti-GST
      VT1A1 and anti-GST-VT2A1 were 76.7% +/- 7.9% and 3.6% +/- 2.3%, respectively, and
      those of VT2 were 1.7% +/- 2.3% and 82.5% +/- 13.9%, respectively. VT2 variant
      toxin was neutralized by anti-GST-VT2A1, with cross neutralization being a
      possible consequence of sequence homology between VT2 and a VT2 variant. To our
      knowledge, this is the first report on the production of polyclonal antibodies
      from GST-VT fusion proteins. The antibodies were shown to exhibit specific toxin
      neutralizing activities and may be useful for immunological diagnosis of VTEC
      infections.

PMID- 11986279
TI  - Comparison of immunoglobulin G subclass profiles induced by measles virus in
      vaccinated and naturally infected individuals.
AB  - A total of 258 human sera positive for measles antibodies were divided into four
      different groups: group 1 contained 54 sera from children after natural measles
      infection (immunoglobulin M [IgM] positive, early infection phase), group 2
      contained 28 sera from children after measles vaccination (IgM positive, early
      infection phase), group 3 contained 100 sera from healthy adults (natural long
      lasting immunity), and group 4 contained 76 sera from healthy children
      (postvaccinal long-lasting immunity). In the early phase of infection, the
      percent distributions of measles virus-specific IgG isotypes were similar between
      natural and postvaccinal immune responses. IgG1 and IgG4 were the dominant
      isotypes, with mean levels of detection of 100% (natural infection) and 100%
      (postvaccinal) for IgG1 and 96% (natural infection) and 92% (postvaccinal) for
      IgG4. In comparison, the IgG4 geometric mean titer (GMT) in the early phase of
      natural infection was significantly higher than the IgG4 GMT detected in the
      postvaccinal immune response (80 versus 13; 95% confidence interval). In the
      memory phase, IgG2 and IgG3 responses decreased significantly in both natural
      infection and postvaccinal groups, while IgG1 levels were maintained. In
      contrast, the IgG4 postvaccinal immune response decreased strongly in the memory
      phase, whereas IgG4 natural long-lasting immunity remained unchanged (9 versus
      86%; P < 0.05). The results obtained suggest that IgG4 isotype could be used in
      the early phase of infection as a quantitative marker and in long-lasting
      immunity as a qualitative marker to differentiate between natural and
      postvaccinal immune responses.

PMID- 11986280
TI  - Importance of M-protein C terminus as substrate antigen for serodetection of
      equine arteritis virus infection.
AB  - Equine arteritis virus (EAV), an enveloped positive-stranded RNA virus, is the
      prototype of the arterivirus group. In a previous paper (A. Kheyar, S. Martin, G.
      St.-Laurent, P. J. Timoney, W. H. McCollum, and D. Archambault, Clin. Diagn. Lab.
      Immunol. 4:648-652, 1997), we have shown that the unglycosylated membrane (M)
      protein, which is composed of 162 amino acids (aa), is a major target of equine
      antibody to EAV. In order to determine the antigenic regions of the M protein,
      the cDNA encoding the M protein of EAV was inserted into the procaryotic
      expression vector pGEX-4T-1 to produce recombinant glutathione S-transferase-M
      fusion protein. Various deletion mutant clones, which covered the entire sequence
      of the M protein, were then generated by inverse PCR and expressed in Escherichia
      coli to examine, by a Western blot assay, the antigenic reactivity of the clone
      derived truncated M proteins with sera from horses either experimentally or
      naturally infected with EAV. Deletion of the hydrophobic N-terminal 87 aa did not
      abolish immune reactivity of the protein with serum antibodies to EAV, thereby
      demonstrating the antigenicity of the C-terminal region (aa 88 to 162) of the M
      protein. Further truncations of the M-protein C-terminal domain defined
      particular linear epitope-containing amino acid sequence regions. However, only
      the M-protein C-terminal region was readily recognized by all EAV-specific horse
      antisera tested in this study. Based on these findings, only the M-protein C
      terminal polypeptide composed of aa 88 to 162 is necessary to identify horse
      serum antibodies specific to the EAV M protein. Thus, this polypeptide might be
      useful for serodetection of EAV-infected animals.

PMID- 11986281
TI  - Cellular immune responses to recombinant antigens in pregnant women chronically
      infected with Toxoplasma gondii.
AB  - The parasite Toxoplasma gondii can infect most mammals and birds, sometimes
      causing severe pathology. Primary infection during pregnancy can result in
      abortion or fetal defects. Host immunity, particularly cellular immunity towards
      antigenic peptides, can control infection, but an efficient vaccine is not yet
      available. We have evaluated T-cell responses to a crude soluble toxoplasma
      antigen (ST-Ag) and to five recombinant peptide antigens of cells in whole-blood
      cultures from 22 pregnant women with preexisting infections and from 7 pregnant
      negative controls. Cells from all infected patients but from none of the controls
      responded specifically to ST-Ag by expressing surface CD25 on culture. Responses
      to the recombinant antigens showed considerable variation between individuals.
      rGRA1 elicited a response in 16 of the 22 samples (73%), rSAG1 in 13, rGRA7 in 9,
      rGRA6-CT in 4, and rGRA6-NT in only 1. Most responding cells were CD4(+). Cells
      from infected subjects cultured with ST-Ag all released high levels of gamma
      interferon (IFN-gamma) into the culture supernatant (4,343 +/- 2,536 pg/ml).
      Cells from 12 patients released IFN-gamma after culture with rGRA1 (130 +/- 98
      pg/ml), those from 10 patients released it after culture with rSAG1 (183 +/- 128
      pg/ml), and those from 4 patients released it after culture with rGRA7 (324 +/-
      374 pg/ml). Intensity of IFN-gamma production in response to the latter two
      recombinant antigens correlated with responses to ST-Ag (r = 0.61 and 0.53,
      respectively; P < 0.01). Interleukin-4 was always absent from supernatants of
      cells stimulated with toxoplasma antigens. The heterogeneity of human responses
      to individual recombinant toxoplasma antigens should be considered in the design
      of potential vaccines.

PMID- 11986282
TI  - Effect of contaminating red blood cells on OKT3-mediated polyclonal activation of
      peripheral blood mononuclear cells.
AB  - Erythrocytes are typically present as impurities in the majority of peripheral
      blood mononuclear cell (PBMC) preparations. This study was undertaken to
      investigate the effects of contaminating red blood cells (RBC) on the ability of
      OKT3 to activate CD4(+) and CD8(+) T cells. Surprisingly, the levels of gamma
      interferon, tumor necrosis factor alpha, and interleukin-1 beta (IL-1 beta)
      produced by PBMC upon stimulation by OKT3 were increased (P < 0.05) in a dose
      dependent manner when increasing amounts of autologous RBC (RBC-to-PBMC ratios of
      2:1, 10:1, and 50:1) were spiked into PBMC preparations. The OKT3-driven
      induction of the IL-2 receptor (CD25) and the proliferation of T lymphocytes in
      response to phorbol myristate acetate were not affected by the addition of RBC.

PMID- 11986283
TI  - Use of reverse transcriptase PCR in early diagnosis of Rift Valley fever.
AB  - Reverse transcriptase PCR (RT-PCR) for diagnosis of Rift Valley fever (RVF) was
      evaluated by using 293 human and animal sera sampled during an RVF outbreak in
      Mauritania in 1998. Results of the RT-PCR diagnostic method were compared with
      those of virus isolation (VI) and detection of immunoglobulin M (IgM) antibodies.
      Our results showed that RT-PCR is a specific, sensitive tool for RVF diagnosis in
      the early phase of the disease and that its results do not differ significantly
      from those obtained by VI. Moreover, the combined results of RT-PCR and IgM
      antibody detection were in 100% concordance with the results of VI.

PMID- 11986284
TI  - One-step PCR to distinguish B virus from related primate alphaherpesviruses.
AB  - By adding betaine to the PCR mixture, we previously established a PCR method to
      amplify a DNA segment of the glycoprotein G gene of B virus (BV) derived from a
      rhesus macaque. We have found that DNA of other BV strains derived from
      cynomolgus, pigtail, and lion-tailed macaques can also serve as the template in
      our PCR assay. Under the same conditions no product was obtained with DNA of
      simian agent 8 of green monkeys and Herpesvirus papio 2 of baboons, or the human
      herpes simplex viruses types 1 and 2. Thus, this PCR method is useful to
      discriminate BV from other closely related primate alphaherpesviruses.

PMID- 11986285
TI  - Increased levels of soluble CD30 in plasma of patients with Plasmodium falciparum
      malaria.
AB  - Levels of soluble CD30 (sCD30) in serum were elevated in patients with Plasmodium
      falciparum malaria but showed decline following treatment. The levels of sCD30 in
      serum were correlated significantly with the expression of gamma interferon by
      peripheral T cells. These data suggest that CD30(+) cells are upregulated during
      a malaria attack and that they may play a regulating role at the site of
      inflammation.

PMID- 11986286
TI  - Development, evaluation, and application of lateral-flow immunoassay
      (immunochromatography) for detection of rotavirus in bovine fecal samples.
AB  - A lateral-flow immunoassay (LFT) was developed to detect bovine rotavirus in
      fecal samples. Using samples (n = 74) from diarrheic calves, a comparison of the
      LFT with a commercial latex agglutination test (LAT) and transmission electron
      microscopy (EM) was conducted. When EM was used as the reference method, initial
      studies of 29 samples indicated 70 and 80% sensitivities of the LFT and LAT,
      respectively, with both being 100% specific. When the LAT was the reference test,
      the LFT was 75% sensitive and 91% specific. Additional specimens (n = 45) were
      tested by the LFT and LAT alone, and results were identical for both methods.

PMID- 11986287
TI  - Assignment of additional anticapsular antibody concentrations to the Neisseria
      meningitidis group A, C, Y, and W-135 meningococcal standard reference serum
      CDC1992.
AB  - We assigned additional enzyme-linked immunosorbent assay antibody concentrations
      (immunoglobulin G [IgG], IgM, and IgA, and total) to the Neisseria meningitidis
      standard reference serum CDC1992 for groups Y and W-135 to 12 Centers for Disease
      Control and Prevention quality control sera. These assignments will supplement
      previous assignments and will aid in the evaluation of present and developing
      vaccines.

PMID- 11986288
TI  - Infection with the helminth Nippostrongylus brasiliensis does not interfere with
      efficient elimination of Mycobacterium bovis BCG from the lungs of mice.
AB  - Infection with Mycobacterium tuberculosis continues to be one of the major global
      health threats. Strong mycobacterium-specific Th1 immune responses correlate with
      protection, and decreased Th1 responses correlate with disease progression. In
      contrast, the impact of Th2 responses on the development of protective immune
      responses to mycobacteria remains unclear. To analyze whether ongoing Th2
      responses present in the lung influence the development of a protective Th1
      immune response to mycobacteria, we coinfected mice with the helminth
      Nippostrongylus brasiliensis and Mycobacterium bovis BCG. We found that the T
      cells from the lymph nodes of coinfected mice secreted significantly less gamma
      interferon than did the T cells from mice infected with M. bovis BCG after in
      vitro stimulation with purified protein from M. tuberculosis when 10(8) CFU of M.
      bovis BCG were used for the infection. This result indicates that the helminth
      infection reduced the Th1 immune response to the mycobacteria in the lung.
      However, mycobacterial clearance was not delayed in the coinfected animals.
      Importantly, the infection with BCG after the helminth infection did not reduce
      the helminth-induced Th2 response in the lung, ruling out the possibility that
      the lack of a reduction in bacterial clearance in the coinfected mice was due to
      a downmodulation of the helminth-induced Th2 response. Taken together, our
      results suggest that ongoing Th2 responses in the lung do not necessarily lead to
      increased susceptibility to mycobacterial infection.

PMID- 11986289
TI  - Activated T lymphocytes disappear from circulation during endotoxemia in humans.
AB  - Seventeen volunteers received an intravenous bolus of endotoxin (2 ng/kg of body
      weight). Endotoxin-induced lymphopenia was constituted mainly by cells with an
      immature phenotype (CD45RA(+) CD45RO(-)) that were less likely to undergo
      apoptosis (CD28(+)), whereas cells with the highest rates of disappearance were
      characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a
      phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced
      lymphopenia reflects the disappearance from the circulation of activated
      lymphocytes prone to undergo apoptosis.

PMID- 11986290
TI  - Helicobacter pylori seroprevalence in asymptomatic pregnant women in France.
AB  - The purpose of our study was to evaluate the incidence of Helicobacter pylori
      seropositivity in two different populations of asymptomatic pregnant women from
      different geographic origins during two separate time periods. A retrospective
      study of consecutive sera obtained from 169 and 302 asymptomatic pregnant women
      in 1990 and 1999, respectively, was carried out. The global H. pylori
      seroprevalences for 1990 and 1999 were 21.3 and 21.5% (where P is
      nonsignificant), respectively. For both periods the H. pylori seroprevalences
      were significantly higher in non-French pregnant women (66.6 and 50.6%) than in
      French pregnant women (18.7 and 11.2%) (P = 0.01 and 0.001, respectively). H.
      pylori seroprevalence in French pregnant women decreased significantly from the
      first period (18.7%) to the second one (11.2%) (P = 0.03).

PMID- 11986291
TI  - Reducing health inequalities--time for optimism.

PMID- 11986292
TI  - Evaluation of the European Union Programme of Community Action on Health
      Promotion, Information, Education and Training 1996-2000.
AB  - The Programme of Community Action on Health Promotion, Information, Education and
      Training 1996-2000 was administered by the European Commission's Services in DGV
      Luxembourg. The programme was a consequence of a decision of the European
      Parliament and the Council of the European Union in March 1996. Middlesex
      University Health Research Centre won the tender to evaluate this programme. In
      this paper the evaluation team disseminate some of the findings that are
      pertinent to the international health promotion community. Key findings include
      significant differences in number of applications and in acceptance rates for
      different Member States. The expert assessors' opinions of the programme suggest
      a number of problems with its administration. Some projects were awarded
      commendably high ratings and others were very weak. The most serious weakness of
      many of the supported projects is lack of any internal evaluation. In order to
      broaden the scope of the second phase of the evaluation of this programme, more
      open communication and dialogue will be needed between all of the stakeholders.
      This implies a change in the culture of the European Commission's Services which,
      in the case of the units involved with this evaluation, are lacking in
      efficiency, openness and transparency.

PMID- 11986293
TI  - Impact evaluation of an oral health intervention amongst primary school children
      in Ireland.
AB  - A pilot oral health programme was developed which aimed to improve dental health
      knowledge and behaviour amongst Irish school children aged 7-12 years. The
      programme comprised two integral components: a television campaign, run over a 6
      week period, was incorporated into the children's programme 'Den TV' on national
      television, with video clips of a member of the music band Boyzone promoting key
      oral health messages; and a Smile of the Year contest. Concurrently, a dental
      nurse delivered an interactive talk with pupils, showed a video of the Den TV
      oral health programme and distributed posters and leaflets. The aim of this study
      was to assess the impact of the overall intervention on school pupils' dental
      health knowledge and reported behaviour. Thirty-two primary schools in two health
      board regions in the Republic of Ireland participated in the study. At baseline
      and after 6 weeks, 1534 school children completed specially developed
      questionnaires. There was a positive net effect of the dental nurse intervention
      in all but one question. The percentage of children who reported using the
      recommended amount of toothpaste and brushing for 3 min appeared to have been
      further increased having observed the television campaign. These results are in
      line with the argument that mass media campaigns work to supplement the one-to
      one activities of health professionals in order to effect knowledge and
      behavioural change.

PMID- 11986294
TI  - Promoting physical activity in women: evaluation of a 2-year community-based
      intervention in Sydney, Australia.
AB  - Women are less likely than men to reach recommended levels of physical activity
      and have unequal access to active leisure time. Studies in Australia have
      consistently found that women are only half as likely as men to be adequately
      active. A community-based multi-strategic health promotion intervention,
      'Concord, A Great Place to be Active', was implemented from 1997 to 1999. It
      aimed to increase the physical activity levels of women aged 20-50 years living
      in the Concord Local Government Area (LGA), an inner-western region of Sydney,
      Australia. A key feature of this intervention was a partnership between Concord
      Council (the local government) and the Central Sydney Health Promotion Unit
      (CSHPU). The project was evaluated using qualitative and quantitative methods.
      Key informant interviews and focus groups were conducted to inform the
      development of the intervention and to assess the impact of the project on
      Concord Council. Pre- and post-intervention telephone surveys of the target group
      were also conducted. Following the intervention, there was a statistically
      significant (6.4%) reduction in the proportion of sedentary women. Further, there
      were a number of positive enhancements in the Council's capacity to promote
      physical activity in the community. These findings demonstrate that a community
      based intervention targeting a specific population can achieve positive changes
      in physical activity and that a local government has the capacity to be involved
      in and sustain physical activity interventions.

PMID- 11986295
TI  - Externalizing and internalizing problems at school as signs of health-damaging
      behaviour and incipient marginalization.
AB  - This study aimed to investigate whether behavioural or emotional problems in
      adolescents detected by their teachers are signs of a common psychosocial
      maladjustment and of the beginning of social marginalization. Altogether, 171
      pupils (15 years of age) from the eastern part of Finland participated in the
      survey. Behavioural and emotional problems and academic achievements were
      assessed separately by two teachers. Pupils filled in a questionnaire about
      alcohol use, smoking, physical exercise and fitness, self-rated health,
      psychosomatic symptoms, social relationships and future educational plans.
      Results showed that poor success at school and the absence of or limited
      educational plans were associated with both externalizing and internalizing
      problems. Externalizing problems were associated with health-damaging behaviour
      and with bullying others. Internalizing problems were associated with poor
      perceived health and a low level of exercise, with mental symptoms, and with
      problems in social relationships. Thus, the pupils in both problem groups had a
      clustering of different risk factors. We conclude that the accumulation in
      adolescents of self-reported health-damaging behaviour, problems related to
      school, to future educational plans and to social relationships are already
      obvious in pupils with externalizing and/ or internalizing problems detected by
      their teachers at the age of 15 years. The capacity of teachers to identify
      pupils at risk as early as possible should therefore be utilized. The development
      of a vicious circle might be prevented through early intervention at school, by
      offering pupils guidance, counselling and treatment.

PMID- 11986296
TI  - The educational experiments of school health promotion for the youth in Japan:
      analysis of the 'sport test' over the past 34 years.
AB  - The objective of this study was to analyze independently the results of a 'sport
      test' that had been conducted in Japanese schools for 34 years without
      interruption, and to examine how physical education in Japanese schools affects
      health promotion in youths and what problems remain to be solved. The source of
      materials for the present study were the Annual Reports on the Survey of Physical
      Fitness and Athletic Ability for the period 1965-1998, published by the Ministry
      of Education, Science, Sports and Culture. Means and standard deviations of total
      scores from physical fitness and athletic ability tests in 11-year-olds (6th
      graders in elementary school), 14-year-olds (3rd graders in junior high school)
      and 17-year-olds (3rd graders in senior high school) were analyzed. The results
      of this study suggest that the trends of changes in mean score and coefficient of
      variation (CV) for physical fitness and athletic ability in Japanese youths are
      associated with the outcome of physical training through physical education in
      school, as well as the effect of the media--mainly television and television
      games. (1) The increase in mean scores and the decrease in CV observed from 1964
      to the first half of the 1970s were probably due to the positive influence of the
      Guideline for Teaching. This guideline emphasized a systematic approach to
      athletic techniques, together with active practice of physical fitness training
      in schools, under the directives of the Boards of Education in response to the
      social 'Physical Fitness Campaign' policy at that time. (2) The leveling off of
      mean scores and CVs observed from the early half of the 1970s to the later half
      of the 1980s might be a result of the invasion of television into Japanese family
      life. (3) The decrease in mean scores and increase in CV observed since the later
      half of the 1980s were assumed to be caused by the negative influence of a
      Guideline for Teaching characterized by the key words 'Physical Education for
      More Pleasure' and a steep increase in the number of television games. (4) In
      terms of methodology, analyzing not only the mean scores but also the CV probably
      provided a more accurate evaluation of the outcome of health promotion in youths.
      In conclusion, strategies for health promotion in youths, especially for proper
      nurturing of physical fitness and athletic ability, should include not only
      delivery of physical fitness training in schools, but also continuous monitoring
      of multiple indicators, and ensuring proper 'Learning of the Body'. The latter
      should include providing learning opportunities centering on the 'body' (not the
      'body' for the sake of labour or military manpower, but one's own 'body' per se);
      guiding young people to recognize the states of their own body and physical
      fitness, and to understand how they can be improved. To be effective in
      implementation, the need to increase the number of professional teachers in
      physical education should be examined. All possible opportunities should also be
      taken to inform youths of the negative effects of television and television
      games, and to encourage them to spend less time on these and more time being
      physically active from the moment they arise.

PMID- 11986297
TI  - Development of a Swedish bicycle helmet promotion programme--one decade of
      experiences.
AB  - OBJECTIVE: to describe 10 years of experiences of the Swedish National Bicycle
      Safety Programme which started during 1990 as part of an initiative taken by the
      World Health Organization (WHO). In relation to WHO's efforts with regard to
      accident and injury prevention, a global programme to increase helmet-wearing by
      two-wheel riders was launched. The idea was to introduce a simple 'vaccine' for
      everyone that was achievable at a low cost. The Swedish initiative was taken up
      by the Karolinska Institute and the National Institute of Public Health. METHOD:
      at an operational level, all available methods and data sources were utilized in
      the programme: surveillance of injuries, provision of information and advice,
      training and supervision, environment and product improvements, and legislation.
      RESULTS: considerable progress has been made in reducing bicycle-related injuries
      in Sweden over the last two decades. Cycling injuries among the elderly must be a
      matter of particular concern. CONCLUSIONS: our 10 years of experiences from a
      bicycle helmet promotion programme lead to the conclusion that there is a case
      for mandatory helmet wearing, as one of the most important strategies on the
      national level. But regional and community-based efforts will still need to be
      more comprehensive. Besides this, efforts must be made to intensify the
      activities of parties already involved in prevention programmes. New target
      groups must be approached, such as immigrants, vulnerable social groups, and
      teenagers. Sustainability of the Swedish Bicycle Helmet Initiative Group,
      including continued participation of group members and organizations, is the key-
      in the long term--to protecting Swedish bicyclists against head injuries.

PMID- 11986298
TI  - Booze and beach bans: turning the tide through community action in New Zealand.
AB  - Many beach and holiday resorts experience major problems with alcohol-related
      public disorder. Following an escalation in alcohol-related incidents in the New
      Zealand beach community of Piha, a community-driven response to address issues of
      community well-being and safety was initiated by concerned residents. A case
      study evaluation reported on the development of a community coalition involving
      community and statutory stakeholders and the successful implementation of local
      community action strategies. These included a beach alcohol ban, extensive local
      publicity and a community policing presence over successive summers. An
      examination of the case study suggests that inter-sectoral collaboration, and
      multiple level strategies through policy, promotion and enforcement activities
      are key factors in enabling communities to successfully reduce alcohol-related
      harm.

PMID- 11986299
TI  - A framework for health promoting emergency departments.
AB  - Since 1986, the World Health Organization (WHO) has been advocating for the
      health sector to move increasingly in a health promotion direction, beyond its
      responsibility for providing clinical and curative services (WHO, 1986). Some
      Emergency Departments (EDs) have partially achieved this through providing
      patient health information, screening and early intervention programs, injury
      prevention and asthma education. While EDs are a suitable setting for health
      promotion, they are grounded in a medical paradigm where most of the staff are
      educated to think exclusively of relation care. As such, a significant
      organizational shift is required for EDs to be more inclusive of health promotion
      principles. Following a comprehensive literature review, a theoretical framework
      was developed for the Health Promoting Emergency Departments Program (HPEDP). It
      describes the opportunities for health promotion in EDs through combining the
      'strategies for health promotion' with the 'spectrum of health and disease'. This
      forms a matrix to enable health development, primary prevention and secondary
      prevention interventions to be planned in EDs. The framework is a tool to support
      the development of coordinate and comprehensive health promotion programs and to
      avoid the use of isolated victim-blaming strategies. Beyond EDs, planners in
      other health care institutions may also find the framework useful-particularly
      those settings where staff health promotion training and experience is limited.

PMID- 11986300
TI  - The limitations of population health as a model for a new public health.
AB  - Population health as developed by the Canadian Institute for Advanced Research
      (CIAR) has influenced the shape and direction of Canadian public health policy,
      and has the potential to do so in the USA and elsewhere. There is reason to be
      concerned about this ascendence of CIAR thinking: population health is rooted
      within epidemiology, a militantly quantitative discipline; population health
      eschews analysis of societal structures as determinants of health; and population
      health elevates scientific understanding over health promotion action. Its lack
      of an explicit values base is also problematic. Policy makers should recognize
      these and other limitations as they consider models for a new public health.

PMID- 11986301
TI  - The extracellular toll-like receptor 2 domain directly binds peptidoglycan
      derived from Staphylococcus aureus.
AB  - Toll-like receptor 2 (TLR2) has been recognized to mediate cell signaling in
      response to peptidoglycan (PGN), a major cell wall component of Gram-positive
      bacteria. The mechanism by which TLR2 recognizes PGN is unknown. It is not even
      clear whether TLR2 directly binds to PGN. In this study, we generated a soluble
      form of recombinant TLR2 (sTLR2) possessing only its putative extracellular
      domain by using the baculovirus expression system to examine the direct
      interaction between sTLR2 and PGN. sTLR2 bound avidly to insoluble PGN (iPGN)
      from Staphylococcus aureus coated onto microtiter wells in a concentration
      dependent manner. In contrast, sTLR2 exhibited a very weak binding to
      lipopolysaccharide. iPGN cosedimented sTLR2 after the mixture of iPGN and sTLR2
      had been incubated and centrifuged. sTLR2 partially attenuated the iPGN-induced
      NF-kappaB activation in TLR2-transfected HEK 293 cells and the iPGN-induced IL-8
      secretion in U937 cells. One of anti-human TLR2 monoclonal antibodies, which
      blocked iPGN-induced NF-kappaB activation in TLR2-transfected cells, inhibited
      the binding of sTLR2 to iPGN. In addition, we found that sCD14 interacted with
      sTLR2 and increased the binding of sTLR2 to iPGN. From these results, we conclude
      that the extracellular TLR2 domain directly binds to PGN.

PMID- 11986302
TI  - Identification of the substrate-binding sites of 2'-5'-oligoadenylate synthetase.
AB  - 2'-5'-Oligoadenylate synthetases are interferon-induced enzymes that upon
      activation by double-stranded RNA polymerize ATP to 2'-5'-linked oligoadenylates.
      In our continuing effort to understand the mechanism of catalysis by these
      enzymes, we used photo affinity cross-linking and peptide mapping to identify the
      substrate-binding sites of the P69 isozyme of human 2'-5'-oligoadenylate
      synthetases. Radiolabeled azido 2'-5'-oligoadenylate dimers were enzymatically
      synthesized and used as ligands for cross-linking to the P69 protein by exposure
      to ultraviolet light. The radiolabeled protein was digested with trypsin, and two
      ligand-cross-linked peptides were purified by immobilized aluminum affinity
      chromatography followed by reverse phase high pressure liquid chromatography. The
      peptides were identified by mass spectrometry and peptide sequencing and were
      found to correspond to residues 420-425 and 539-547 of P69. To examine the
      functional importance of the cross-linking sites, specific residues in the two
      peptides were mutated. When residues in the two sites were mutated individually,
      ligand cross-linking was selectively eliminated at the mutated site, and the
      enzyme activity was lost almost completely. Using substrates that can serve
      either as a donor or as an acceptor but not both, we could identify one of the
      sites as the acceptor and the other as the donor site.

PMID- 11986303
TI  - Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation.
AB  - Hydrogen peroxide is implicated as an intracellular messenger in various cellular
      responses such as proliferation and differentiation. Peroxiredoxin (Prx) I is a
      member of the peroxiredoxin family of peroxidases and contains a consensus site
      (Thr(90)-Pro-Lys-Lys) for phosphorylation by cyclin-dependent kinases (CDKs).
      This protein has now been shown to be phosphorylated specifically on Thr(90) by
      several CDKs, including Cdc2, in vitro. Phosphorylation of Prx I on Thr(90)
      reduced the peroxidase activity of this protein by 80%. The phosphorylation of
      Prx I in HeLa cells was monitored with the use of antibodies specific for Prx I
      phosphorylated on Thr(90). Immunoblot analysis with these antibodies of HeLa
      cells arrested at various stages of the cell cycle revealed that Prx I
      phosphorylation occurs in parallel with the activation of Cdc2; Prx I
      phosphorylation was thus marked during mitosis but virtually undetectable during
      interphase. Furthermore, when Cdc2 expression was reduced by RNA interference
      with cognate small interfering RNAs, Prx I phosphorylation was not observed in
      the cells synchronized in mitotic phase. The cytosolic location of Prx I likely
      prevents its interaction with activated CDKs until after the breakdown of the
      nuclear envelope during mitosis, when Cdc2 is the CDK that is most active.
      Phosphorylation of Prx I on Thr(90) both in vitro and in vivo was blocked by
      roscovitine, an inhibitor of CDKs. These results suggest that Cdc2-mediated
      phosphorylation and inactivation of Prx I and the resulting intracellular
      accumulation of H(2)O(2) might be important for progression of the cell cycle.

PMID- 11986304
TI  - Lymphoid enhancer factor-1 blocks adenomatous polyposis coli-mediated nuclear
      export and degradation of beta-catenin. Regulation by histone deacetylase 1.
AB  - The oncogenic protein beta-catenin is overexpressed in many cancers, frequently
      accumulating in nuclei where it forms active complexes with lymphoid enhancer
      factor-1 (LEF-1)/T-cell transcription factors, inducing genes such as c-myc and
      cyclin D1. In normal cells, nuclear beta-catenin levels are controlled by the
      adenomatous polyposis coli (APC) protein through nuclear export and cytoplasmic
      degradation. Transient expression of LEF-1 is known to increase nuclear beta
      catenin levels by an unknown mechanism. Here, we show that APC and LEF-1 compete
      for nuclear beta-catenin with opposing consequences. APC can export nuclear beta
      catenin to the cytoplasm for degradation. In contrast, LEF-1 anchors beta-catenin
      in the nucleus by blocking APC-mediated nuclear export. LEF-1 also prevented the
      APC/CRM1-independent nuclear export of beta-catenin as revealed by in vitro
      assays. Importantly, LEF-1-bound beta-catenin was protected from degradation by
      APC and axin in SW480 colon cancer cells. The ability of LEF-1 to trap beta
      catenin in the nucleus was down-regulated by histone deacetylase 1, and this
      correlated with a decrease in LEF1 transcription activity. Our findings identify
      LEF-1 as key regulator of beta-catenin nuclear localization and stability and
      suggest that overexpression of LEF-1 in colon cancer and melanoma cells may
      contribute to the accumulation of oncogenic beta-catenin in the nucleus.

PMID- 11986305
TI  - Psathyrella velutina Mushroom Lectin Exhibits High Affinity toward
      Sialoglycoproteins Possessing Terminal N-Acetylneuraminic Acid alpha 2,3-Linked
      to Penultimate Galactose Residues of Trisialyl N-Glycans. Comparison with other
      sialic acid-specific lectins.
AB  - A lectin from the fruiting body of the Psathyrella velutina mushroom (PVL) was
      found to bind specifically to N-acetylneuraminic acid, as well as to GlcNAc
      (Ueda, H., Kojima, K., Saitoh, T., and Ogawa, H. (1999) FEBS Lett. 448, 75-80).
      In this study, the glycan sequences that PVL recognizes with high affinity on
      sialoglycoproteins were revealed. Among sialic acid-specific lectins only PVL
      could reveal the sialylated N-acetyllactosamine structure of glycoproteins in
      blotting studies, based on the dual specificity. The affinity of PVL to fetuin
      was measured by surface plasmon resonance to be 10(7) m(-1), which is an order of
      magnitude higher than those of Sambucus nigra agglutinin and Maackia amurensis
      mitogen, whereas affinity to asialofetuin was approximately 0 and to asialo
      agalactofetuin was 10(8) m(-1), suggesting that PVL exhibits remarkably high
      affinities toward glycoproteins possessing trisialo- or GlcNAc-exposed glycans.
      Transferrin was separated into fractions that correspond to the sialylation
      states on an immobilized PVL column. Transferrin-possessing trisialoglycans
      containing alpha2,3-linked N-acetylneuraminic acid on the beta1,4-linked GlcNAc
      branch bound to the PVL column and eluted with GlcNAc; those containing only
      alpha2,6-linked sialic acids were retarded, whereas other transferrin fractions
      passed through the column. These results indicate that PVL is a lectin with
      potential for separation and detection of sialoglycoproteins because of its dual
      specificity toward sialoglycans and GlcNAc exposed glycans.

PMID- 11986306
TI  - Thermodynamics of the pyruvate kinase reaction and the reversal of glycolysis in
      heart and skeletal muscle.
AB  - The effect of temperature, pH, and free [Mg(2+)] on the apparent equilibrium
      constant of pyruvate kinase (phosphoenol transphosphorylase) (EC ) was
      investigated. The apparent equilibrium constant, K', for the biochemical reaction
      P-enolpyruvate + ADP = ATP + Pyr was defined as K' = [ATP][Pyr]/[ADP][P
      enolpyruvate], where each reactant represents the sum of all the ionic and metal
      complexed species in M. The K' at pH 7.0, 1.0 mm free Mg(2+) and I of 0.25 m was
      3.89 x 10(4) (n = 8) at 25 degrees C. The standard apparent enthalpy (DeltaH'
      degrees ) for the biochemical reaction was -4.31 kJmol(-1) in the direction of
      ATP formation. The corresponding standard apparent entropy (DeltaS' degrees ) was
      +73.4 J K(-1) mol(-1). The DeltaH degrees and DeltaS degrees values for the
      reference reaction, P-enolpyruvate(3-) + ADP(3-) + H(+) = ATP(4-) + Pyr(1-), were
      -6.43 kJmol(-1) and +180 J K(-1) mol(-1), respectively (5 to 38 degrees C). We
      examined further the mass action ratio in rat heart and skeletal muscle at rest
      and found that the pyruvate kinase reaction in vivo was close to equilibrium i.e.
      within a factor of about 3 to 6 of K' in the direction of ATP at the same pH,
      free [Mg(2+)], and T. We conclude that the pyruvate kinase reaction may be
      reversed under some conditions in vivo, a finding that challenges the long held
      dogma that the reaction is displaced far from equilibrium.

PMID- 11986307
TI  - The RFX family interacts at the collagen (COL1A2) start site and represses
      transcription.
AB  - The transcription start site of the collagen alpha2(1) gene (COL1A2) has a
      sequence-specific binding site for a DNA methylation-responsive binding protein
      called regulatory factor for X-box 1 (RFX1) (Sengupta, P. K., Erhlich, M., and
      Smith, B. D. (1999) J. Biol. Chem. 274, 36649-36655). In this report, we
      demonstrate that RFX1 forms homodimers as well as heterodimers with RFX2 spanning
      the collagen transcription start site. Methylation at +7 on the coding strand
      increases RFX1 complex formation in gel shift assays. Methylation on the template
      strand, however, does not increase RFX1 complex formation. DNA from human
      fibroblasts contains minimal methylation on the coding strand (<4%) with variable
      methylation on the template strand. RFX1 acts as a repressor of collagen
      transcription as judged by in vitro transcription and co-transfection assays with
      an unmethylated collagen promoter-reporter construct. In addition, an RFX5
      complex present in human fibroblasts interacts with the collagen RFX site, which
      is not sensitive to methylation. This is the first demonstration of RFX5 complex
      formation on a gene other than major histocompatibility complex (MHC) promoters.
      Also, RFX5 represses transcription of a collagen promoter-reporter construct in
      rat fibroblasts that have no detectable RFX5 complex formation or protein. RFX5
      complex activates MHC II transcription by interacting with an interferon-gamma
      (IFN-gamma)-inducible protein, major histocompatibility class II trans-activator
      (CIITA). Collagen transcription is repressed by IFN-gamma in a dose-dependent
      manner in human but not in rat fibroblasts. IFN-gamma enhances RFX5 binding
      activity, and CIITA is present in the RFX5 complex of IFN-gamma-treated human
      fibroblasts. CIITA repressed collagen gene transcription more effectively in
      human fibroblasts than in rat fibroblasts, suggesting that the RFX5 complex may,
      in part, recruit CIITA protein to the collagen transcription start site. Thus the
      RFX family may be important repressors of collagen gene transcription through a
      RFX binding site spanning the transcription start site.

PMID- 11986308
TI  - Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA
      substrate interactions and cleavage site determination.
AB  - Flap endonuclease-1 (FEN-1) is a critical enzyme for DNA replication and repair.
      Intensive studies have been carried out on its structure-specific nuclease
      activities and biological functions in yeast cells. However, its specific
      interactions with DNA substrates as an initial step of catalysis are not defined.
      An understanding of the ability of FEN-1 to recognize and bind a flap DNA
      substrate is critical for the elucidation of its molecular mechanism and for the
      explanation of possible pathological consequences resulting from its failure to
      bind DNA. Using human FEN-1 in this study, we identified two positively charged
      amino acid residues, Arg-47 and Arg-70 in human FEN-1, as candidates responsible
      for substrate binding. Mutation of the Arg-70 significantly reduced flap
      endonuclease activity and eliminated exonuclease activity. Mutation or
      protonation of Arg-47 shifted cleavage sites with flap substrate and
      significantly reduced the exonuclease activity. We revealed that these
      alterations are due to the defects in DNA-protein interactions. Although the
      effect of the single Arg-47 mutation on binding activities is not as severe as
      R70A, its double mutation with Asp-181 had a synergistic effect. Furthermore the
      possible interaction sites of these positively charged residues with DNA
      substrates were discussed based on FEN-1 cleavage patterns using different
      substrates. Finally data were provided to indicate that the observed negative
      effects of a high concentration of Mg(2+) on enzymatic activity are probably due
      to the competition between the arginine residues and metal ions with DNA
      substrate since mutants were found to be less tolerant.

PMID- 11986309
TI  - Isolation of cyanophycin-degrading bacteria, cloning and characterization of an
      extracellular cyanophycinase gene (cphE) from Pseudomonas anguilliseptica strain
      BI. The cphE gene from P. anguilliseptica BI encodes a cyanophycinhydrolyzing
      enzyme.
AB  - Eleven bacteria capable of utilizing cyanophycin (cyanophycin granule polypeptide
      (CGP)) as a carbon source for growth were isolated. One isolate was taxonomically
      affiliated as Pseudomonas anguilliseptica strain BI, and the extracellular
      cyanophycinase (CphE) was studied because utilization of cyanophycin as a carbon
      source and extracellular cyanophycinases were hitherto not described. CphE was
      detected in supernatants of CGP cultures and purified from a corresponding
      culture of strain BI employing chromatography on the anion exchange matrix Q
      Sepharose and on an arginine-agarose affinity matrix. The mature form of the
      inducible enzyme consisted of one type of subunit with M(r) = 43,000 and
      exhibited high specificity for CGP, whereas proteins and synthetic polyaspartic
      acid were not hydrolyzed or were only marginally hydrolyzed. Degradation products
      of the enzyme reaction were identified as aspartic acid-arginine dipeptides (beta
      Asp-Arg) by high performance liquid chromatography and electrospray ionization
      mass spectrometry. The corresponding gene (cphE, 1254 base pairs) was identified
      in subclones of a cosmid gene library of strain BI by heterologous active
      expression in Escherichia coli, and its nucleotide sequence was determined. The
      enzyme exhibited only 27-28% amino acid sequence identity to intracellular
      cyanophycinases occurring in cyanobacteria. Analysis of the amino acid sequence
      of cphE revealed a putative catalytic triad consisting of the motif GXSXG plus a
      histidine and most probably a glutamate residue. In addition, the strong
      inhibition of the enzyme by Pefabloc((R)) and phenylmethylsulfonyl fluoride
      indicated that the catalytic mechanism of CphE is related to that of serine type
      proteases. Quantitative analysis on the release of beta-Asp-Arg dipeptides from C
      terminal labeled CGP gave evidence for an exo-degradation mechanism.

PMID- 11986310
TI  - Direct interaction of proliferating cell nuclear antigen with the small subunit
      of DNA polymerase delta.
AB  - The interaction between proliferating cell nuclear antigen (PCNA) and DNA
      polymerase delta is essential for processive DNA synthesis during DNA
      replication/repair; however, the identity of the subunit of DNA polymerase delta
      that directly interacts with PCNA has not been resolved until now. In the present
      study we have used reciprocal co-immunoprecipitation experiments to determine
      which of the two subunits of core DNA polymerase delta, the 125-kDa catalytic
      subunit or the 50-kDa small subunit, directly interacts with PCNA. We found that
      PCNA co-immunoprecipitated with human p50, as well as calf thymus DNA polymerase
      delta heterodimer, but not with p125 alone, suggesting that PCNA directly
      interacts with p50 but not with p125. A PCNA-binding motif, similar to the
      sliding clamp-binding motif of bacteriophage RB69 DNA polymerase, was identified
      in the N terminus of p50. A 22-amino acid oligopeptide containing this sequence
      (MRPFL) was shown to bind PCNA by far Western analysis and to compete with p50
      for binding to PCNA in co-immunoprecipitation experiments. The binding of p50 to
      PCNA was inhibited by p21, suggesting that the two proteins compete for the same
      binding site on PCNA. These results establish that the interaction of PCNA with
      DNA polymerase delta is mediated through the small subunit of the enzyme.

PMID- 11986311
TI  - Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor
      2, and heparin via its b1b2 domain.
AB  - Neuroplin-1 (NRP1), a receptor for vascular endothelial growth factor (VEGF)
      family members, has three distinct extracellular domains, a1a2, b1b2, and c. To
      determine the VEGF(165) and placenta growth factor 2 (PlGF-2)-binding sites of
      NRP1, recombinant NRP1 domains were expressed in mammalian cells as Myc-tagged,
      soluble proteins, and used in co-precipitation experiments with 125I-VEGF165 and
      125I-PlGF-2. Anti-Myc antibodies immunoprecipitated 125I-VEGF165 and 125I-PlGF-2
      in the presence of the b1b2 but not of the a1a2 and c domains. Neither b1 nor b2
      alone was capable of binding 125I-VEGF165. In competition experiments, VEGF165
      competed PlGF-2 binding to the NRP1 b1b2 domain, suggesting that the binding
      sites of VEGF165 and PlGF-2 overlap. The presence of the a1a2 domain greatly
      enhanced VEGF165, but not PlGF-2 binding to b1b2. Heparin enhanced the binding of
      both 125I-VEGF165 and 125I-PlGF-2 to the b1b2 domain by 20- and 4-fold,
      respectively. A heparin chain of at least 20-24 monosaccharides was necessary for
      binding. In addition, the b1b2 domain of NRP1 could bind heparin directly,
      requiring heparin oligomers of at least 8 monosaccharide units. It was concluded
      that an intact b1b2 domain serves as the VEGF165-, PlGF-2-, and heparin-binding
      sites in NRP1, and that heparin is a critical component for regulating VEGF165
      and PlGF-2 interactions with NRP1 by physically interacting with both receptor
      and ligands.

PMID- 11986312
TI  - Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast
      cells.
AB  - After attachment to receptors, reovirus virions are internalized by endocytosis
      and exposed to acid-dependent proteases that catalyze viral disassembly. Previous
      studies using the cysteine protease inhibitor E64 and a mutant cell line that
      does not support reovirus disassembly suggest a requirement for specific
      endocytic proteases in reovirus entry. This study identifies the endocytic
      proteases that mediate reovirus disassembly in murine fibroblast cells. Infection
      of both L929 cells treated with the cathepsin L inhibitor Z-Phe-Tyr(t-Bu)
      diazomethyl ketone and cathepsin L-deficient mouse embryo fibroblasts resulted in
      inefficient proteolytic disassembly of viral outer-capsid proteins and decreased
      viral yields. In contrast, both L929 cells treated with the cathepsin B inhibitor
      CA-074Me and cathepsin B-deficient mouse embryo fibroblasts support reovirus
      disassembly and growth. However, removal of both cathepsin B and cathepsin L
      activity completely abrogates disassembly and growth of reovirus. Concordantly,
      cathepsin L mediates reovirus disassembly more efficiently than cathepsin B in
      vitro. These results demonstrate that either cathepsin L or cathepsin B is
      required for reovirus entry into murine fibroblasts and indicate that cathepsin L
      is the primary mediator of reovirus disassembly. Moreover, these findings suggest
      that specific endocytic proteases can determine host cell susceptibility to
      infection by intracellular pathogens.

PMID- 11986313
TI  - Mouse DTEF-1 (ETFR-1, TEF-5) is a transcriptional activator in alpha 1-adrenergic
      agonist-stimulated cardiac myocytes.
AB  - alpha(1)-Adrenergic signaling in cardiac myocytes activates the skeletal muscle
      alpha-actin gene through an MCAT cis-element, the binding site of the
      transcriptional enhancer factor-1 (TEF-1) family of transcription factors. TEF-1
      accounts for more than 85% of the MCAT binding activity in neonatal rat cardiac
      myocytes. Other TEF-1 family members account for the rest. Although TEF-1 itself
      has little effect on the alpha(1)-adrenergic activation of skeletal muscle alpha
      actin, the related factor RTEF-1 augments the response and is a target of
      alpha(1)-adrenergic signaling. Here, we examined another TEF-1 family member
      expressed in cardiac muscle, DTEF-1, and observed that it also augmented the
      alpha(1)-adrenergic response of skeletal muscle alpha-actin. A DTEF-1 peptide
      specific antibody revealed that endogenous DTEF-1 accounts for up to 5% of the
      MCAT binding activity in neonatal rat cardiac myocytes. A TEF-1/DTEF-1 chimera
      suggests that alpha(1)-adrenergic signaling modulates DTEF-1 function.
      Orthophosphate labeling and immunoprecipitation of an epitope-tagged DTEF-1
      showed that DTEF-1 is phosphorylated in vivo. alpha(1)-Adrenergic stimulation
      increased while phosphatase treatment lowered the MCAT binding by DTEF-1 and the
      endogenous non-TEF-1 MCAT-binding factor. In contrast, alpha(1)-adrenergic
      stimulation did not alter, and phosphatase treatment increased, MCAT binding of
      TEF-1 and RTEF-1. Taken together, these results suggest that DTEF-1 is a target
      for alpha(1)-adrenergic activation of the skeletal muscle alpha-actin gene in
      neonatal rat cardiac myocytes.

PMID- 11986314
TI  - Identification and characterization of a novel rat ov-serpin family member,
      trespin.
AB  - Serpins are responsible for regulating a variety of proteolytic processes through
      a unique irreversible suicide substrate mechanism. To discover novel genes
      regulated by transforming growth factor-beta1 (TGF-beta 1), we performed
      differential display reverse transcriptase-PCR analysis of NRP-152 rat prostatic
      epithelial cells and cloned a novel rat serpin that is transcriptionally down
      regulated by TGF-beta and hence named trespin (TGF-beta-repressible serine
      proteinase inhibitor (trespin). Trespin is a 397-amino acid member of the ov
      serpin clade with a calculated molecular mass of 45.2 kDa and 72% amino acid
      sequence homology to human bomapin; however, trespin exhibits different tissue
      expression, cellular localization, and proteinase specificity compared with
      bomapin. Trespin mRNA is expressed in many tissues, including brain, heart,
      kidney, liver, lung, prostate, skin, spleen, and stomach. FLAG-trespin expressed
      in HEK293 cells is localized predominantly in the cytoplasm and is not
      constitutively secreted. The presence of an arginine at the P1 position of
      trespin's reactive site loop suggests that trespin inhibits trypsin-like
      proteinases. Accordingly, in vitro transcribed and translated trespin forms
      detergent-stable and thermostable complexes with plasmin and elastase but not
      subtilisin A, trypsin, chymotrypsin, thrombin, or papain. Trespin interacts with
      plasmin at a near 1:1 stoichiometry, and immunopurified mammal-expressed trespin
      inhibits plasmin in a dose-dependent manner. These data suggest that trespin is a
      novel and functional member of the rat ov-serpin family.

PMID- 11986315
TI  - Expression of endomembrane calcium pumps in colon and gastric cancer cells.
      Induction of SERCA3 expression during differentiation.
AB  - Calcium mobilization from the endoplasmic reticulum (ER) into the cytosol is a
      key component of several signaling networks controlling tumor cell growth,
      differentiation, or apoptosis. Sarco/endoplasmic reticulum calcium transport
      ATPases (SERCA-type calcium pumps), enzymes that accumulate calcium in the ER,
      play an important role in these phenomena. We report that SERCA3 expression is
      significantly reduced or lost in colon carcinomas when compared with normal
      colonic epithelial cells, which express this enzyme at a high level. To study the
      involvement of SERCA enzymes in differentiation, in this work differentiation of
      colon and gastric cancer cell lines was initiated, and the change in the
      expression of SERCA isoenzymes as well as intracellular calcium levels were
      investigated. Treatment of the tumor cells with butyrate or other established
      differentiation inducing agents resulted in a marked and specific induction of
      the expression of SERCA3, whereas the expression of the ubiquitous SERCA2 enzymes
      did not change significantly or was reduced. A similar marked increase in SERCA3
      expression was found during spontaneous differentiation of post-confluent Caco-2
      cells, and this closely correlated with the induction of other known markers of
      differentiation. Analysis of the expression of the SERCA3 alternative splice
      isoforms revealed induction of all three known iso-SERCA3 variants (3a, 3b, and
      3c). Butyrate treatment of the KATO-III gastric cancer cells led to higher
      resting cytosolic calcium concentrations and, in accordance with the lower
      calcium affinity of SERCA3, to diminished ER calcium content. These data taken
      together indicate a defect in SERCA3 expression in colon cancers as compared with
      normal colonic epithelium, show that the calcium homeostasis of the endoplasmic
      reticulum may be remodeled during cellular differentiation, and indicate that
      SERCA3 constitutes an interesting new differentiation marker that may prove
      useful for the analysis of the phenotype of gastrointestinal adenocarcinomas.

PMID- 11986316
TI  - Opposing action of estrogen receptors alpha and beta on cyclin D1 gene
      expression.
AB  - Induction of cyclin D1 gene transcription by estrogen receptor alpha (ERalpha)
      plays an important role in estrogen-mediated proliferation. There is no classical
      estrogen response element in the cyclin D1 promoter, and induction by ERalpha has
      been mapped to an alternative response element, a cyclic AMP-response element at 
      57, with possible participation of an activating protein-1 site at -954. The
      action of ERbeta at the cyclin D1 promoter is unknown, although evidence suggests
      that ERbeta may inhibit the proliferative action of ERalpha. We examined the
      response of cyclin D1 promoter constructs by luciferase assay and the response of
      the endogenous protein by Western blot in HeLa cells transiently expressing
      ERalpha, ERalphaK206A (a derivative that is superactive at alternative response
      elements), or ERbeta. In each case, ER activation at the cyclin D1 promoter is
      mediated by both the cyclic AMP-response element and the activating protein-1
      site, which play partly redundant roles. The activation by ERbeta occurs only
      with antiestrogens. Estrogens, which activate cyclin D1 gene expression with
      ERalpha, inhibit expression with ERbeta. Strikingly, the presence of ERbeta
      completely inhibits cyclin D1 gene activation by estrogen and ERalpha or even by
      estrogen and the superactive ERalphaK206A. The observation of the opposing action
      and dominance of ERbeta over ERalpha in activation of cyclin D1 gene expression
      has implications for the postulated role of ERbeta as a modulator of the
      proliferative effects of estrogen.

PMID- 11986317
TI  - The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis,
      and proliferation are differentiation stage-specific.
AB  - FAZF, a member of the BTB/POZ family of transcriptional repressor proteins, has
      been shown to bind to FANCC, the protein defective in patients with the bone
      marrow failure syndrome Fanconi anemia complementation group C. Because bone
      marrow failure in Fanconi anemia has been attributed to a failure of the
      hematopoietic stem cell population to produce sufficient progeny, we documented
      the expression of FAZF in human CD34(+) hematopoietic progenitor cells. FAZF was
      expressed at high levels in early stages of differentiation but declined during
      subsequent differentiation into erythroid and myeloid lineages. Consistent with
      its presumed role as a transcriptional repressor, FAZF was found in the nuclear
      compartment, where it resides in distinct nuclear speckles at or near sites of
      DNA replication. Using a FAZF-inducible myeloid cell line, we found that enforced
      expression of FAZF was accompanied by accumulation in the G(1) phase of the cell
      cycle followed later by apoptosis. These results suggest an essential role for
      FAZF during the proliferative stages of primitive hematopoietic progenitors,
      possibly acting in concert with (a subset of) the Fanconi anemia proteins.

PMID- 11986318
TI  - The human papillomavirus oncoprotein E7 attenuates NF-kappa B activation by
      targeting the Ikappa B kinase complex.
AB  - Infection with high-risk human papillomaviruses (HPV) can lead to the development
      of cervical carcinomas. This process critically depends on the virus-encoded E6
      and E7 oncoproteins, which stimulate proliferation by manipulating the function
      of a variety of host key regulatory proteins. Here we show that both viral
      proteins dose-dependently interfere with the transcriptional activity of NF
      kappaB. A variety of experimental approaches revealed that a fraction of the E7
      proteins is found in association with the IkappaB kinase complex and attenuates
      induced kinase activity of IkappaB kinase alpha (IKKalpha) and IKKbeta, thus
      resulting in impaired IkappaBalpha phosphorylation and degradation. Indirect
      immunofluorescence shows that E7 impairs TNFalpha-induced nuclear translocation
      of NF-kappaB, thus preventing NF-kappaB from binding to its cognate DNA. While E7
      obviates IKK activation in the cytoplasm, the E6 protein reduces NF-kappaB p65
      dependent transcriptional activity within the nucleus. We suggest that HPV
      oncogene-mediated suppression of NF-kappaB activity contributes to HPV escape
      from the immune system.

PMID- 11986319
TI  - The donor substrate specificity of the human beta 1,3-glucuronosyltransferase I
      toward UDP-glucuronic acid is determined by two crucial histidine and arginine
      residues.
AB  - The human beta1,3-glucuronosyltransferase I (GlcAT-I) plays a key role in
      proteoglycan biosynthesis by catalyzing the transfer of glucuronic acid onto the
      trisaccharide-protein linkage structure Galbeta1,3Galbeta1,4Xylbeta-O-Ser, a
      prerequisite step for polymerization of glycosaminoglycan chains. In this study,
      we identified His(308) and Arg(277) residues as essential determinants for the
      donor substrate (UDP-glucuronic acid) selectivity of the human GlcAT-I. Analysis
      of the UDP-glucuronic acid-binding site by computational modeling in conjunction
      with site-directed mutagenesis indicated that both residues interact with
      glucuronic acid. Substitution of His(308) by arginine induced major changes in
      the donor substrate specificity of GlcAT-I. Interestingly, the H308R mutant was
      able to efficiently utilize nucleotide sugars UDP-glucose, UDP-mannose, and UDP-N
      acetylglucosamine, which are not naturally accepted by the wild-type enzyme, as
      co-substrate in the transfer reaction. To gain insight into the role of Arg(277),
      site-directed mutagenesis in combination with chemical modification was carried
      out. Substitution of Arg(277) with alanine abrogated the activity of GlcAT-I.
      Furthermore, the arginine-directed reagent 2,3-butanedione irreversibly inhibited
      GlcAT-I, which was effectively protected against inactivation by UDP-glucuronic
      acid but not by UDP-glucose. It is noteworthy that the activity of the H308R
      mutant toward UDP-glucose was unaffected by the arginine-directed reagent. Our
      results are consistent with crucial interactions between the His(308) and
      Arg(277) residues and the glucuronic acid moiety that governs the specificity of
      GlcAT-I toward the nucleotide sugar donor substrate.

PMID- 11986320
TI  - Gal80 confers specificity on HAT complex interactions with activators.
AB  - Several yeast transcription activators have been shown to interact with and
      recruit histone acetyltransferase complexes to promoters in chromatin. The
      promiscuity of activator/HAT interactions suggests that additional factors
      temporally regulate these interactions in response to signaling pathways. In this
      study, we demonstrate that the negative regulator, Gal80, blocks interactions
      between the SAGA and NuA4 HAT complexes and the Gal4 activator. By contrast,
      Gal80 did not inhibit SAGA and NuA4 interaction with another activator Gcn4. The
      function of Gal80 prevented Gal4 targeting of SAGA and displaced SAGA targeted by
      Gal4 to a promoter within a nucleosome array. In the same set of experiments,
      targeting of SAGA by Gcn4 was unaffected by Gal80. These studies demonstrate that
      the specificity of HAT/activator interactions can be dictated by cofactors that
      modulate activation domain function in response to cellular signals.

PMID- 11986321
TI  - Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human
      Fcgamma RIII and antibody-dependent cellular toxicity.
AB  - Lec13 cells, a variant Chinese hamster ovary cell line, were used to produce
      human IgG1 that were deficient in fucose attached to the Asn(297)-linked
      carbohydrate but were otherwise similar to that found in IgG1 produced in normal
      Chinese hamster ovary cell lines and from human serum. Lack of fucose on the IgG1
      had no effect on binding to human FcgammaRI, C1q, or the neonatal Fc receptor.
      Although no change in affinity was found for the His(131) polymorphic form of
      human FcgammaRIIA, a slight improvement in binding was evident for FcgammaRIIB
      and the Arg(131) FcgammaRIIA polymorphic form. In contrast, binding of the fucose
      deficient IgG1 to human FcgammaRIIIA was improved up to 50-fold. Antibody
      dependent cellular cytotoxicity assays using purified peripheral blood monocytes
      or natural killer cells from several donors showed enhanced cytotoxicity,
      especially evident at lower antibody concentrations. When combined with an IgG1
      Fc protein variant that exhibited enhanced antibody-dependent cellular
      cytotoxicity, the lack of fucose was synergistic.

PMID- 11986322
TI  - Role of p50/CDC37 in hepadnavirus assembly and replication.
AB  - The cellular chaperone Hsp90 has been shown to associate with the reverse
      transcriptase (RT) of the duck hepatitis B virus and is required for RT
      functions. However, the molecular basis for the specific interaction between the
      RT and Hsp90 remains unknown. Comparison of protein compositional properties
      suggests that the RT is highly related to the protein kinase c-Raf, which
      interacts with Hsp90 via the cochaperone p50 (CDC37). We tested whether the RT,
      like c-Raf, is specifically recognized by p50. Immunoprecipitation and pull-down
      assays showed that p50 or p50deltaC, a p50 mutant defective in Hsp90 binding,
      could interact specifically with the RT both in vitro and in vivo, indicating
      that p50 can bind the RT independently of Hsp90. Furthermore, purified p50 and
      p50deltaC interacted directly with purified RT. The importance of p50-RT
      interaction for RT functions was underscored by 1) inhibition of protein-primed
      initiation of reverse transcription by p50deltaC in vitro and 2) stimulation of
      viral DNA replication and RNA packaging by p50 and their inhibition by p50deltaC
      in transfected cells. These results suggest that p50 can function as a cellular
      cofactor for the hepadnavirus RT by mediating the interaction between the RT and
      Hsp90.

PMID- 11986323
TI  - Truncated, inactive N-acetylglucosaminyltransferase III (GlcNAc-TIII) induces
      neurological and other traits absent in mice that lack GlcNAc-TIII.
AB  - N-Acetylglucosaminyltransferase III (GlcNAc-TIII), the product of the Mgat3 gene,
      transfers the bisecting GlcNAc to the core mannose of complex N-glycans. The
      addition of this residue is regulated during development and has functional
      consequences for receptor signaling, cell adhesion, and tumor progression. Mice
      homozygous for a null mutation at the Mgat3 locus (Mgat3(Delta)) or for a
      targeted mutation in the Mgat3 gene (previously called Mgat3(neo), but herein
      renamed Mgat3(T37) because the allele generates inactive GlcNAc-TIII of
      approximately 37 kDa) were found to exhibit retarded progression of liver tumors.
      Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of
      neutral N-glycans from kidneys revealed no significant differences, and both
      mutants showed the expected lack of N-glycan species with an additional GlcNAc.
      However, the two mutants differed in several biological traits. Mgat3(T37/T37)
      homozygotes in a mixed or 129(SvJ) background were retarded in growth rate and
      exhibited an altered leg clasp reflex, an altered gait, and defective nursing
      behavior. Pups abandoned by Mgat3(T37/T37) mothers were rescued by wild-type
      foster mothers. None of these Mgat3(T37/T37) traits were exhibited by
      Mgat3(Delta/Delta) mice or by heterozygous mice carrying the Mgat3(T37) mutation.
      Similarly, no dominant-negative effect was observed in Chinese hamster ovary
      cells expressing truncated GlcNAc-TIII in the presence of wild-type GlcNAc-TIII.
      However, compound heterozygotes carrying both the Mgat3(T37) and Mgat3(Delta)
      mutations exhibited a marked leg clasp reflex, indicating that in the absence of
      wild-type GlcNAc-TIII, truncated GlcNAc-TIII causes this phenotype. The Mgat3
      gene was expressed in brain at embryonic day 10.5 and thereafter and in neurons
      of adult cerebellum. The mutant Mgat3 gene was also highly expressed in
      Mgat3(T37/T37) brain. This may be the basis of the unexpected neurological
      phenotype induced by truncated, inactive GlcNAc-TIII in the mouse.

PMID- 11986324
TI  - Dominant Saccharomyces cerevisiae msh6 mutations cause increased mispair binding
      and decreased dissociation from mispairs by Msh2-Msh6 in the presence of ATP.
AB  - A previous study described four dominant msh6 mutations that interfere with both
      the Msh2-Msh6 and Msh2-Msh3 mismatch recognition complexes (Das Gupta, R., and
      Kolodner, R. D. (2000) Nat. Genet. 24, 53-56). Modeling predicted that two of the
      amino acid substitutions (G1067D and G1142D) interfere with protein-protein
      interactions at the ATP-binding site-associated dimer interface, one (S1036P)
      similarly interferes with protein-protein interactions and affects the Msh2 ATP
      binding site, and one (H1096A) affects the Msh6 ATP-binding site. The ATPase
      activity of the Msh2-Msh6-G1067D and Msh2-Msh6-G1142D complexes was inhibited by
      GT, +A, and +AT mispairs, and these complexes showed increased binding to GT and
      +A mispairs in the presence of ATP. The ATPase activity of the Msh2-Msh6-S1036P
      complex was inhibited by a GT mispair, and it bound the GT mispair in the
      presence of ATP, whereas its interaction with insertion mispairs was unchanged
      compared with the wild-type complex. The ATPase activity of the Msh2-Msh6-H1096A
      complex was generally attenuated, and its mispair-binding behavior was
      unaffected. These results are in contrast to those obtained with the wild-type
      Msh2-Msh6 complex, which showed mispair-stimulated ATPase activity and ATP
      inhibition of mispair binding. These results indicate that the dominant msh6
      mutations cause more stable binding to mispairs and suggest that there may be
      differences in how base base and insertion mispairs are recognized.

PMID- 11986325
TI  - Cercarial elastase is encoded by a functionally conserved gene family across
      multiple species of schistosomes.
AB  - Water borne cercaria(ae) of the trematode genus Schistosoma rapidly penetrate
      host skin. A single serine protease activity, cercarial elastase, is deposited in
      advance of the invading parasite by holocytosis of vesicles from ten large
      acetabular gland cells. Cercarial elastase activity is a composite of multiple
      isoforms. Genes coding for the isoforms can be divided into two classes by amino
      acid and promoter sequence homology. Two of the five genes identified in
      Schistosoma mansoni account for over 90% of the activity and protein released.
      The remaining genes produce little protein or are silent. Positional scanning
      synthetic combinatorial substrate libraries demonstrate that the two major
      isoforms have similar substrate specificities and are, therefore, isoenzymes. The
      closely related Schistosoma hematobium and the distantly related Schistosomatium
      douthitti also contain multiple orthologous cercarial elastase genes suggesting
      that gene duplication may have occurred after speciation in Schistosoma evolution
      and that this duplication has been conserved.

PMID- 11986326
TI  - Structures of lipopolysaccharides from Klebsiella pneumoniae. Eluicidation of the
      structure of the linkage region between core and polysaccharide O chain and
      identification of the residues at the non-reducing termini of the O chains.
AB  - Deamination of LPSs from Klebsiella pneumoniae released O-chain polysaccharides
      together with a fragment of the core oligosaccharide. The structures of the
      products from serotypes O1, O2a, O2a,c, O3, O4, O5, and O12 were determined by
      NMR spectroscopy and chemical methods, identifying the linkage region between the
      O antigens and the core as well as novel residues at the non-reducing ends of the
      polysaccharides. All serotypes had an identical linkage between the O chain and
      core.

PMID- 11986327
TI  - Cloning and characterization of human Siglec-11. A recently evolved signaling
      molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue
      macrophages, including brain microglia.
AB  - Siglecs are sialic acid-recognizing animal lectins of the immunoglobulin
      superfamily. We have cloned and characterized a novel human molecule, Siglec-11,
      that belongs to the subgroup of CD33/Siglec-3-related Siglecs. As with others in
      this subgroup, the cytosolic domain of Siglec-11 is phosphorylated at tyrosine
      residue(s) upon pervanadate treatment of cells and then recruits the protein
      tyrosine phosphatases SHP-1 and SHP-2. However, Siglec-11 has several novel
      features relative to the other CD33/Siglec-3-related Siglecs. First, it binds
      specifically to alpha2-8-linked sialic acids. Second, unlike other CD33/Siglec-3
      related Siglecs, Siglec-11 was not found on peripheral blood leukocytes. Instead,
      we observed its expression on macrophages in various tissues, such as liver
      Kupffer cells. Third, it was also expressed on brain microglia, thus becoming the
      second Siglec to be found in the nervous system. Fourth, whereas the Siglec-11
      gene is on human chromosome 19, it lies outside the previously described
      CD33/Siglec-3-related Siglec cluster on this chromosome. Fifth, analyses of
      genome data bases indicate that Siglec-11 has no mouse ortholog and that it is
      likely to be the last canonical human Siglec to be reported. Finally, although
      Siglec-11 shows marked sequence similarity to human Siglec-10 in its
      extracellular domain, the cytosolic tail appears only distantly related. Analysis
      of genomic regions surrounding the Siglec-11 gene suggests that it is actually a
      chimeric molecule that arose from relatively recent gene duplication and
      recombination events, involving the extracellular domain of a closely related
      ancestral Siglec gene (which subsequently became a pseudogene) and a
      transmembrane and cytosolic tail derived from another ancestral Siglec.

PMID- 11986328
TI  - Estrogen-related receptor alpha 1 actively antagonizes estrogen receptor
      regulated transcription in MCF-7 mammary cells.
AB  - The estrogen-related receptor alpha (ERRalpha) is an orphan member of the nuclear
      receptor superfamily. We show that the major isoform of the human ERRalpha gene,
      ERRalpha1, can sequence-specifically bind a consensus palindromic estrogen
      response element (ERE) and directly compete with estrogen receptor alpha
      (ERalpha) for binding. ERRalpha1 activates or represses ERE-regulated
      transcription in a cell type-dependent manner, repressing in ER-positive MCF-7
      cells while activating in ER-negative HeLa cells. Thus, ERRalpha1 can function
      both as a modulator of estrogen responsiveness and as an estrogen-independent
      activator. Repression likely occurs in the absence of exogenous ligand since
      charcoal treatment of the serum had no effect on silencing activity. Mutational
      analysis revealed that repression is not simply the result of competition between
      ERalpha and ERRalpha1 for binding to the DNA. Rather, it also requires the
      presence of sequences within the carboxyl-terminal E/F domain of ERRalpha1. Thus,
      ERRalpha1 can function as either an active repressor or a constitutive activator
      of ERE-dependent transcription. We hypothesize that ERRalpha1 can play a critical
      role in the etiology of some breast cancers, thereby providing a novel
      therapeutic target in their treatment.

PMID- 11986329
TI  - Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to
      mature anchoring fibril collagen.
AB  - Collagen VII is the major structural component of the anchoring fibrils at the
      dermal-epidermal junction in the skin. It is secreted by keratinocytes as a
      precursor, procollagen VII, and processed into mature collagen during
      polymerization of the anchoring fibrils. We show that bone morphogenetic protein
      1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C
      terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1
      consensus cleavage site SYAA/DTAG within the NC-2 domain. Mammalian tolloid-like
      (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to
      process procollagen VII at the same site in vitro. Immunohistochemical and
      genetic evidence supported the involvement of these enzymes in cleaving type VII
      procollagen in vivo. Both BMP-1 and mTLL-1 are expressed in the skin and in
      cultured cutaneous cells. A naturally occurring deletion in the human COL7A1
      gene, 8523del14, which is associated with dystrophic epidermolysis bullosa and
      eliminates the BMP-1 consensus sequence, abolished processing of procollagen VII,
      and in mutant skin procollagen VII accumulated at the dermal-epidermal junction.
      On the other hand, deficiency of BMP-1 in the skin of knockout mouse embryos did
      not prevent processing of procollagen VII to mature collagen, suggesting that
      mTLL-1 and/or mTLL-2 can substitute for BMP-1 in the processing of procollagen
      VII in situ.

PMID- 11986330
TI  - A highly active homeobox gene promoter regulated by Ets and Sp1 family members in
      normal granulosa cells and diverse tumor cell types.
AB  - One mechanism by which normal cells become converted to tumor cells involves the
      aberrant transcriptional activation of genes that are normally silent. We
      characterize a promoter that normally exhibits highly tissue- and stage-specific
      expression but displays ubiquitous expression when cells become immortalized or
      malignant, regardless of their lineage or tissue origin. This promoter normally
      drives the expression of the Pem homeobox gene in specific cell types in ovary
      and placenta but is aberrantly expressed in lymphomas, neuroblastomas,
      retinoblastomas, carcinomas, and sarcomas. By deletion analysis we identified a
      region between nucleotides -80 and -104 that was absolutely critical for the
      expression from this distal Pem promoter (Pem Pd). Site-specific mutagenesis and
      transfection studies revealed that this region contains two consensus Ets sites
      and a single Sp1 site that were necessary for Pem Pd expression. Gel shift
      analysis showed that Ets and Sp1 family members bound to these sites.
      Transfection studies demonstrated that the Ets family members Elf1 and Gabp and
      the Sp1 family members Sp1 and Sp3 transactivated the Pem Pd. Surprisingly, we
      found that Sp3 was a more potent activator of the Pem Pd than was Sp1; this is
      unusual, because Sp3 is either a weak activator or a repressor of most other
      promoters. Activation by either Elf1 or Gabp required an intact Sp1 family member
      binding site, suggesting that Ets and Sp1 family members cooperate to activate
      Pem Pd transcription. Expression from the Pem Pd (either transiently transfected
      or endogenous) depended on the Ras pathway, which could explain both its Ets- and
      Sp1-dependent expression in normal cells and its aberrant expression in tumor
      cells, in which ras protooncogenes are frequently mutated. We suggest that the
      Pem Pd may be a useful model system to understand the molecular mechanism by
      which a tissue-specific promoter can be corrupted in tumor cells.

PMID- 11986331
TI  - Autophosphorylation of the mammalian multifunctional protein that initiates de
      novo pyrimidine biosynthesis.
AB  - CAD, a large multifunctional protein that carries carbamoyl phosphate synthetase
      (CPSase), aspartate transcarbamoylase, and dihydroorotase activities, catalyzes
      the first three steps of de novo pyrimidine biosynthesis in mammalian cells. The
      CPSase component, which catalyzes the initial, rate-limiting step, exhibits
      complex regulatory mechanisms involving allosteric effectors and phosphorylation
      that control the flux of metabolites through the pathway. Incubation of CAD with
      ATP in the absence of exogenous kinases resulted in the incorporation of 1 mol of
      P(i)/mol of CAD monomer. Mass spectrometry analysis of tryptic digests showed
      that Thr(1037) located within the CAD CPS.B subdomain was specifically modified.
      The reaction is specific for MgATP, ADP was a competitive inhibitor, and the
      native tertiary structure of the protein was required. Phosphorylation occurred
      after denaturation, further purification of CAD by SDS gel electrophoresis, and
      renaturation on a nitrocellulose membrane, strongly suggesting that phosphate
      incorporation resulted from an intrinsic kinase activity and was not the result
      of contaminating kinases. Chemical modification with the ATP analog, 5'-p
      fluorosulfonylbenzoyladenosine, showed that one or both of the active sites that
      catalyze the ATP-dependent partial reactions are also involved in
      autophosphorylation. The rate of phosphorylation was dependent on the
      concentration of CAD, indicating that the reaction was, at least in part,
      intermolecular. Autophosphorylation resulted in a 2-fold increase in CPSase
      activity, an increased sensitivity to the feedback inhibitor UTP, and decreased
      allosteric activation by 5-phosphoribosyl-1-pyrophosphate, functional changes
      that were distinctly different from those resulting from phosphorylation by
      either the protein kinase A or mitogen-activated protein kinase cascades.

PMID- 11986332
TI  - beta 1 integrin regulates fibroblast viability during collagen matrix contraction
      through a phosphatidylinositol 3-kinase/Akt/protein kinase B signaling pathway.
AB  - Integrins regulate cell viability through their interaction with the
      extracellular matrix. Integrins can sense mechanical forces arising from the
      matrix and convert these stimuli to chemical signals capable of modulating
      intracellular signal transduction. The phosphatidylinositol 3-kinase (PI3K)/Akt
      signaling pathway is a major regulator of cell survival. It is not known,
      however, whether integrins, acting as mechanoreceptors, regulate cell survival
      via the PI3K/Akt pathway. Here, we show that in response to a matrix-derived
      mechanical stimulus, beta1 integrin regulated cell viability by regulating Akt
      activity in a PI3K-dependent fashion. To accomplish this, we employed fibroblasts
      cultured in collagen gels. During contraction of collagen matrices, fibroblasts
      underwent apoptosis. We demonstrate that ligation of beta1 integrin with anti
      beta1 integrin antibodies protected fibroblasts from apoptosis. The nature of the
      survival signal activated by beta1 integrin engagement with antibody was mediated
      by PI3K acting through Akt/protein kinase B. We show that Akt phosphorylation
      decreased during collagen contraction and that this decrease correlated precisely
      with the onset of fibroblast apoptosis. Fibroblasts transfected with
      constitutively active PI3K displayed increased Akt phosphorylation and were
      protected from anoikis and collagen gel contraction-induced apoptosis. Our data
      identify a novel role for beta1 integrin in regulating fibroblast viability
      through a PI3K/Akt/protein kinase B signaling pathway in response to a matrix
      derived mechanical stimulus.

PMID- 11986333
TI  - Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas?
AB  - Uterine carcinosarcomas (malignant mixed Mullerian tumours) are highly aggressive
      and have traditionally been regarded as a subtype of uterine sarcoma. However, in
      recent years convincing evidence has suggested that most, but not all, are
      monoclonal in origin rather than true collision tumours. Data confirm that the
      carcinomatous element is the "driving force" and that the sarcomatous component
      is derived from the carcinoma or from a stem cell that undergoes divergent
      differentiation. Thus, uterine carcinosarcomas are best regarded as metaplastic
      carcinomas, although the designation carcinosarcoma is likely to remain. Adjuvant
      treatment for uterine carcinosarcoma should probably be similar to that directed
      against aggressive high grade endometrial carcinomas rather than being sarcoma
      based. Importantly, a small proportion of uterine carcinosarcomas are true
      collision tumours and should be recognised as such because, in some instances,
      the prognosis may be better than for a similar stage carcinosarcoma.

PMID- 11986334
TI  - Diagnosis of premalignant endometrial disease.
AB  - Modern molecular methods for precancer diagnosis have expanded the range of
      detectable disease to a preclinical level and provided material for
      histopathological correlation. The precancer scenario begins with sporadic
      acquisition of rare PTEN mutation bearing glands, which are morphologically
      unremarkable, and progresses to discrete foci of cytologically altered glands,
      readily visible on routinely stained sections. Clinical outcome studies of women
      with endometrial lesions have established threshold diagnostic features that
      confer increased cancer risk. This class of high risk lesions has been designated
      endometrial intraepithelial neoplasia (EIN). EIN is diagnosed by presence of
      cytological demarcation, crowded gland architecture, minimum size of 1mm, and
      careful exclusion of mimics. Most EIN lesions have been diagnosed as atypical
      endometrial hyperplasias in the World Health Organisation system. Specialised
      molecular and morphometric analyses have been extremely useful in redefining
      clinically relevant premalignant endometrial disease, but translation to improved
      patient care requires the informed participation of pathologists.

PMID- 11986335
TI  - Multidrug resistance related molecules in human and murine lung.
AB  - AIMS: Transporter proteins known to mediate multidrug resistance (MDR) in tumour
      cells--MDR1 P-glycoprotein (P-gp) and multidrug resistance related protein 1
      (MRP1)--are thought to be involved in protecting the lungs against inhaled toxic
      pollutants. Recently, several new transporter family members have been identified
      -for example, MRP2, MRP3, and breast cancer resistance protein (BCRP). To study
      the possible contribution of these proteins and the earlier defined MDR1 and MDR3
      P-gp molecules, MRP1, and the major vault protein (MVP) to lung functioning,
      their expression was analysed in normal lung tissue of humans and several animal
      species. METHODS: Frozen sections of normal lung tissues were examined for the
      expression of the multidrug resistance associated proteins, using an extended
      panel of monoclonal antibodies that specifically detect these proteins in
      immunohistochemical techniques. RESULTS: In line with earlier reports, the
      expression of MDR1 P-gp and MRP1 was readily detected in the apical and
      basolateral membranes, respectively, of the epithelial cell layers of the lungs.
      In addition, prominent cytoplasmic MVP staining was detected in these layers. In
      contrast, the recently discovered transporters were either undetectable or they
      were present at very low values in lung tissue. Immunohistochemical staining in
      tissues from mice, rats, and guinea pigs points to a strong evolutionary
      conservation for these transporter proteins. CONCLUSIONS: These results show that
      the "classic" MDR related molecules, MDR1 P-gp, MRP1, and MVP, should be
      considered the most important transporters in normal lung physiology. It will be
      of great interest to investigate differences in expression of both classic and
      newly defined transporters between normal individuals and-for example, patients
      with various bronchopulmonary pathological conditions.

PMID- 11986336
TI  - Pancreatic cancer after remote peptic ulcer surgery.
AB  - BACKGROUND: Peptic ulcer surgery may carry an increased risk for pancreatic
      cancer development. Molecular analysis of K-ras codon 12, frequently mutated in
      conventional pancreatic cancers, might provide insight into the aetiological
      mechanisms. METHODS: The relative risk of pancreatic cancer was computed by
      multivariate and person-year analysis in a cohort of 2633 patients who had
      undergone gastrectomy. Lung cancer risk was analysed as an indirect means of
      assessing smoking behaviour. K-ras codon 12 mutational analysis was performed on
      15 postgastrectomy pancreatic cancers. RESULTS: There was an overall increased
      risk of pancreatic carcinoma of 1.8 (95% confidence interval, 1.3 to 2.6) five to
      59 years postoperatively, which gradually increased to 3.6 at 35 years or more
      after surgery (chi(2) test for trend, p < 0.05). Multivariate analysis indicated
      that parameters other than postoperative interval did not influence the risk.
      Lung cancer risk was significantly increased after surgery, but no time trend was
      observed. The spectrum and prevalence of K-ras codon 12 mutations were comparable
      to conventional pancreatic cancer. CONCLUSIONS: Remote partial gastrectomy is
      associated with an increased risk of pancreatic cancer. Postgastrectomy and non
      postgastrectomy pancreatic cancers may share similar aetiological factors, such
      as smoking. However, the neoplastic process in patients who have undergone
      gastrectomy appears to be accelerated by factors related to the surgery itself.

PMID- 11986338
TI  - A clinicopathological study of 152 surgically treated primary gastric lymphomas
      with survival analysis of 109 high grade tumours.
AB  - AIMS: To describe the clinicopathological features of a large number of
      surgically treated and followed up primary gastric lymphomas and thereby gain a
      better understanding of their biology, with particular reference to the
      prognostic factors of high grade tumours. METHODS: A retrospective study of 152
      patients. RESULTS: High grade gastric lymphomas, both pure and with a residual
      low grade component, differed from low grade mucosa associated lymphoid tissue
      (MALT)-type lymphomas in that they were more frequently large, ulcerated, at an
      advanced stage, and highly proliferating. In addition, patients were older and
      had a worse outcome. The prognosis of high grade lymphomas was influenced by
      patient age, tumour stage, depth of infiltration in the gastric wall, and the
      invasion of adjacent organs. Adjuvant postsurgical treatment prolonged survival
      only in patients with advanced stage and deep neoplastic infiltration.
      CONCLUSIONS: There is a sharp distinction between low grade MALT-type lymphomas
      and tumours with a high grade component, justifying their different treatment
      approach. The postsurgical management of high grade lymphomas should be based on
      the accurate evaluation of the neoplastic extension.

PMID- 11986340
TI  - Foveolar hyperplasia at the gastric cardia: prevalence and associations.
AB  - AIMS: In the gastric antrum and body, foveolar hyperplasia is a feature of
      reactive gastritis resulting from--for example, duodenogastric bile reflux and
      the use of non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study
      was to examine the occurrence and clinical relevance of gastric cardiac foveolar
      hyperplasia. METHODS: The study population was drawn from a consecutive series of
      1698 patients sent for upper gastrointestinal endoscopy. Only cases without
      chronic gastritis or Barrett's oesophagus were included. The final study
      population consisted of 307 patients. RESULTS: Foveolar hyperplasia was seen in
      the gastric cardiac mucosa in 31 (10%) patients with histologically normal
      stomach mucosa, but none had endoscopically noticeable hyperplastic polyps.
      Compared with patients without gastric cardiac hyperplasia, those with
      hyperplasia more often had chronic inflammation and complete intestinal
      metaplasia in the junctional biopsies (48% v 77% and 9% v 26%, respectively).
      Logistic regression analysis revealed that chronic cardiac inflammation (odds
      ratio (OR), 3.2; 95% confidence interval (CI), 1.3 to 7.8) and intestinal
      metaplasia of the complete type (OR, 2.8; 95% CI, 1.1 to 7.1) were independent
      risk factors for cardiac foveolar hyperplasia. In univariate analysis, endoscopic
      erosive oesophagitis (endoscopy positive gastro-oesophageal reflux disease) and
      the use of NSAIDs were not related to the presence of foveolar hyperplasia.
      CONCLUSIONS: Foveolar hyperplasia in the gastric cardiac mucosa occurs in
      patients with histologically normal non-gastritic stomachs and may develop as a
      consequence of chronic inflammation limited to the gastro-oesophageal junction
      ("junctitis"). It is not associated directly with endoscopy positive gastro
      oesophageal reflux disease or the use of NSAIDs.

PMID- 11986341
TI  - Prevalence of antibodies to Chlamydia pneumoniae in an Israeli population without
      clinical evidence of respiratory infection.
AB  - AIMS: To estimate the occurrence of recent, past, and "persistent" infections
      with Chlamydia pneumoniae--as indicated by serology--in an Israeli population
      without clinical evidence of respiratory infection. METHODS: Serum samples from
      402 subjects (172 children and 230 adults), without known respiratory symptoms,
      were collected. Antibodies to C pneumoniae (IgG, IgA, and IgM) were evaluated
      using the microimmunofluorescence (MIF) assay. Antibody prevalence and indication
      of recent, past, and persistent infections were calculated and their distribution
      determined according to age, sex, and season. RESULTS: Antibodies to C pneumoniae
      were detected in 53 children (31%) and 171 adults (74%). Recent infection was
      indicated in only one of 50 children under 5 years of age, in nine of 122 older
      children, and in 19 of 230 adults. IgM antibodies were detected in nine children,
      but only in three adults. Past infection was indicated in six of 96 young
      children (aged 1-10 years), in 28 of 76 teenagers, and in 128 of 230 adults.
      Persistent infection was indicated in three young children, in six teenagers, and
      in 24 adults, with a significantly higher frequency (p = 0.012) in men (18 of
      117) than in women (six of 113). No seasonal differences could be detected.
      CONCLUSIONS: Infection with C pneumoniae was detected serologically in children
      and adults without clinical signs of respiratory disease. These results should
      serve as a basis for studies on the role of C pneumoniae infections and their
      sequelae in Israel and contribute to the general understanding of asymptomatic
      infection with C pneumoniae.

PMID- 11986342
TI  - Multiparameter flow cytometry as a tool for the detection of micrometastatic
      tumour cells in the sentinel lymph node procedure of patients with breast cancer.
AB  - AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used
      for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast
      cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n =
      238) from 98 patients were analysed. For each lymph node, sections for
      haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for
      cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The
      intervening material was used for MP-FCM. Cells were immunostained with MNF116,
      followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat
      antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph
      node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of
      the 98 patients with breast carcinoma showed evidence of metastatic disease in
      the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic
      cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive
      cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2
      mm (macrometastasis) and in 14 these foci were smaller than 2 mm
      (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs,
      although this was not seen at first glance in the H&E or IHC sections. After
      revision of the slides, one of these three remained negative. However, MP-FCM
      analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which
      was almost identical to that of the primary breast tumour. Duplicate
      measurements, done in 41 cases, showed a 99% reproducibility. In five of 14
      patients with micrometastasis, one or two metastatic foci were found in the non
      SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have
      metastatic tumour. All micrometastases except for the remaining negative one
      mentioned above showed only diploid tumour cells, despite the fact that their
      primary tumours contained both diploid and aneuploid tumour cells. In primary
      tumours with more than 60% aneuploid cells, predominantly aneuploid
      macrometastasis were found, whereas diploid primary tumours only showed diploid
      micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases
      were associated with non-SLN metastases in five of seven patients, whereas
      diploid cases showed additional non-SLN metastases in only seven of 16 patients.
      CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour
      cells in a large volume of lymph node tissue from SLNs. In some cases it was
      superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are
      accompanied by additional non-SLN metastases. The size of the aneuploid fraction
      (> 60%) in the primary tumour may influence the risk of having both SLN and non
      SLN metastases.

PMID- 11986343
TI  - Thromboxane synthase immunohistochemistry in inflammatory bowel disease.
AB  - BACKGROUND: Thromboxanes are produced in excess in inflammatory bowel disease.
      Preliminary reports suggest that ridogrel, a thromboxane synthase inhibitor, is
      anti-inflammatory and may have therapeutic benefits in patients with ulcerative
      colitis. AIMS: To investigate the immunohistochemical expression of thromboxane
      synthase in the colorectal mucosa of patients with inflammatory bowel disease.
      METHODS: Immunostaining of colonic biopsies from patients with inflammatory bowel
      disease (n = 13) and controls (n = 5) was performed using a monoclonal antibody
      to human thromboxane synthase. The extent of staining in cells of the lamina
      propria was compared in patient and control groups, and was assessed in relation
      to disease activity scored macroscopically and histologically. RESULTS: The
      percentage of cells in the lamina propria staining for thromboxane synthase was
      higher in patients with active inflammatory bowel disease than in those with
      inactive disease or in controls (p = 0.02 and p = 0.002, respectively). There was
      a direct correlation between disease activity, measured endoscopically and
      histologically, and the percentage of lamina propria cells staining for
      thromboxane synthase (R = 0.71, p = 0.001 and R = 0.72, p = 0.001, respectively).
      CONCLUSIONS: Increased thromboxane synthase expression in lamina propria cells
      occurs in active inflammatory bowel disease. It is possible that this results in
      increased thromboxane synthesis, which may in turn contribute to mucosal
      inflammation and intramucosal thrombogenesis.

PMID- 11986344
TI  - Distinct expression patterns of ER alpha and ER beta in normal human mammary
      gland.
AB  - AIM: Two oestrogen receptors (ERs) have been identified to date-the "classic" ER
      alpha and the more recently described ER beta. Although much is known about ER
      alpha at the mRNA and protein levels, our knowledge of the expression and
      distribution of ER beta protein is much more limited. The aim of this study was
      to compare the cellular distribution of ER alpha and ER beta in normal human
      mammary gland. METHODS: Formalin fixed, paraffin wax embedded material was
      obtained from reduction mammoplasty specimens, normal tissue adjacent to breast
      tumour, or fibroadenoma. Sections were immunohistochemically stained for ER
      alpha, ER beta, and the progesterone receptor. The staining pattern for each
      antibody was evaluated and compared. RESULTS: ER alpha was restricted to the cell
      nuclei of epithelial cells lining ducts and lobules. Although ER beta was also
      seen in these cells, additional strong staining was detected specifically in the
      cell nuclei of myoepithelial cells. Occasional staining was seen in surrounding
      stromal and endothelial cell nuclei and in lymphocytes. CONCLUSIONS: ER subtypes
      have distinct distribution patterns in the normal mammary gland. The widespread
      distribution of ER beta suggests that it may be the dominant ER in the mammary
      gland where it may be acting as a natural suppressor.

PMID- 11986345
TI  - Validation of a simple, rapid, and economical technique for distinguishing type 1
      and 2 fibres in fixed and frozen skeletal muscle.
AB  - AIMS: To produce a method of distinguishing between type 1 and 2 skeletal muscle
      fibres that would be more economical and reproducible than the standard ATPase
      method and be applicable to both fixed and frozen tissue. Because the ATPase
      method has been accepted as the basis for fibre identification for the past 50
      years, the new method should not give significantly different results. METHODS:
      Isoforms of myosin correlate with isoforms of myofibrillar ATPase and an
      immunohistochemical (IHC) double labelling protocol was devised using monoclonal
      antibodies to fast and slow myosin. This required one tissue section rather than
      four. The results of the two methods were compared by means of morphometric
      analysis of skeletal muscle biopsies from 20 normal healthy volunteers. RESULTS:
      There were no significant differences (p = 0.57) in the percentages of type 1
      (46% using the IHC method v 48% using ATPase) or type 2 fibres (54% v 52%,
      respectively). The 2a and 2b subtypes were distinguished easily. Analysis of
      variance revealed that cross sectional area (mu m(2)), diameter (mu m), form
      factor, and density of fibre staining (a measure of substrate-enzyme or protein)
      were all similar. The method worked equally well on fixed material. CONCLUSION:
      An IHC method based on the fast and slow isoforms of myosin shows no significant
      differences in fibre type analysis from the standard ATPase method although it
      provides important advantages because it is applicable to fixed (including
      archival) material, is economical and reproducible, and yields a permanent
      preparation.

PMID- 11986346
TI  - The expression of bone morphogenetic proteins in osteosarcoma and its relevance
      as a prognostic parameter.
AB  - AIMS: The expression of bone morphogenetic proteins (BMPs) was analysed in 47
      osteosarcomas to determine differences in the expression of BMP subtypes and to
      correlate expression with response to chemotherapy, in addition to the disease
      free and overall survival of patients. METHODS: The expression of BMPs was
      examined immunohistochemically in 47 biopsy specimens of osteosarcoma using
      commercially available antibodies against different subtypes (BMP-2/4 (A-20), BMP
      3 (N-19), BMP-4 (N-19), BMP-5 (N-19), BMP-6 (N-19), BMP-7 (N-19), BMP-8 (N-19)).
      The avidin-biotin-immunoperoxidase method was used for all antibodies. RESULTS:
      The expression of BMP subtypes varied considerably: 28 of the 47 tumours
      expressed BMP-2/4, 24 expressed BMP-3, 41 expressed BMP-5, 31 expressed BMP-6, 43
      expressed BMP-7, and 42 expressed BMP-8. High expression of BMP-6 was found in
      those parts of the osteosarcoma with a chondroid differentiation (p = 0.016, Mann
      Whitney test). No correlation was observed between the response to chemotherapy
      and the expression of BMPs (p > 0.05, Mann-Whitney test). Univariate analysis
      showed no correlation between overall survival or progression free survival and
      the expression of BMPs (p > 0.05, log rank test). CONCLUSIONS: BMP-7 and BMP-8
      are highly expressed in osteosarcoma. Moreover, high expression of BMP-6
      correlates with a chondroid differentiation. In contrast to conclusions derived
      from previous studies in which small numbers of tumours were investigated, these
      results indicate that the expression of BMPs does not help to predict the outcome
      of patients.

PMID- 11986347
TI  - The influence of nodal size on the staging of colorectal carcinomas.
AB  - AIMS: The reliable identification of node negative colorectal carcinomas (CRCs)
      has often been linked to the histological examination of a minimum number of
      lymph nodes. The sizes of the lymph nodes, their metastatic status, and their
      number were investigated to establish whether these parameters are related, and
      whether their relation could help in determining the adequacy of staging.
      METHODS: One thousand three hundred and thirty four negative lymph nodes, 189
      metastatic lymph nodes, and 43 pericolonic/perirectal tumour deposits measuring >
      or = 3 mm from 60 node positive and from 63 node negative patients with CRC were
      assessed for size. RESULTS: The mean size (SD) of these structures was 4.5 (2.7)
      mm. The lymph nodes were significantly larger in the CRCs with metastatic nodes
      (4.7 v 4.3 mm). Involved nodes were significantly larger than negative nodes (6.3
      v 4.2 mm), despite the fact that the largest node was < or = 5 mm in one third of
      node positive CRCs. The examination of the seven largest nodes could have
      adequately staged 97% of node positive CRCs and 98% of all CRCs. CONCLUSIONS: The
      nodal staging of CRCs is dependent not only on the number of lymph nodes
      investigated, but also on qualitative features of the lymph nodes assessed,
      including their size. Lymph nodes are not equivalent and any study neglecting
      this fact will give grounds for error in the recommendation of a minimum number
      of nodes for the reliable determination of node negative CRCs. Although
      pathologists should aim to recover all nodes, a negative nodal status based on
      only seven nodes can be reliable.

PMID- 11986349
TI  - CD10 is useful in demonstrating endometrial stroma at ectopic sites and in
      confirming a diagnosis of endometriosis.
AB  - AIMS: Recent studies have shown that CD10 is a useful immunohistochemical marker
      of normal endometrial stroma and of endometrial stromal neoplasms. The aim of
      this study was to investigate whether CD10 immunoreactivity is present in ectopic
      endometrial stroma and whether staining is of value in confirming a diagnosis of
      endometriosis. METHODS/RESULTS: Twenty five cases of endometriosis were stained
      with a commercially available antibody against CD10. Endometrial stromal cells
      were positive in 22 of 25 cases. There was little or no staining of other
      tissues. CONCLUSIONS: CD10 immunoreactivity is largely maintained in endometrial
      stromal cells located outside the uterus. Immunohistochemical staining with CD10
      may be of value in confirming a diagnosis of endometriosis when there is
      morphological doubt.

PMID- 11986350
TI  - Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?
AB  - BACKGROUND: An increase in intraepithelial lymphocytes (IELs) is mandatory for
      the histological diagnosis of coeliac disease (CD). Currently, duodenal biopsies
      are used almost exclusively to establish the diagnosis, yet published work
      continues to cite an upper limit of 40 lymphocytes/100 epithelial cells, a figure
      derived from jejunal biopsies over 30 years ago. AIM: To establish the normal
      range for IEL counts in distal duodenal biopsies. MATERIALS/METHODS: Twenty
      subjects (seven men, 13 women; median age, 34 years; range, 20-65) with a normal
      sugar permeability test and concurrent distal duodenal biopsies were identified.
      The number of IELs and epithelial cell nuclei in an uninterrupted length of
      surface (villous) epithelium (> 500 cells) was counted. An image analysis system
      was used to assess villous architecture by calculating the villous height to
      crypt depth ratio. RESULTS: The range of IEL counts in 20 subjects was 1.8-26/100
      villous epithelial cells, with a mean value of 11 and SD of 6.8. The mean villous
      to crypt ratio was 1.82 (SD, 0.38; range, 1.22-2.46). There was no correlation
      between IEL counts and villous to crypt ratio (Spearman rank correlation, -0.066;
      p = 0.80). CONCLUSIONS: These results suggest that 25 IELs/100 epithelial cells
      (mean +2 SD) should be taken as the upper limit of the normal range for duodenal
      mucosa.

PMID- 11986351
TI  - Lack of CD34 positive stromal cells within angiomyomas (vascular leiomyomas).
AB  - AIMS: To investigate the role of CD34 positive stromal cells in the morphogenesis
      and tumour growth regulation of angiomyomas (vascular leiomyomas). METHODS:
      Histochemical analysis using monoclonal antibodies to CD34 and CD31 was performed
      in 10 angiomyomas and their adjacent soft tissue. RESULTS: CD34 positive stromal
      cells were not seen within the tumour tissue; the thick walled vessels within the
      tumours lacked CD34 positive stromal cells. In contrast, bundles of CD34 positive
      stromal cells were detected at the tumour border of all of the angiomyomas and in
      the adventitial tissue of the surrounding normal vessels. CONCLUSIONS: The lack
      of CD34 positive stromal cells within an angiomyoma is associated with the
      characteristic morphology of an angiomyoma.

PMID- 11986352
TI  - Oesophagobronchial fistula caused by varicella zoster virus in a patient with
      AIDS: a unique case.
AB  - Human herpesvirus oesophagitis in human immunodeficiency virus positive patients
      is caused by cytomegalovirus and herpes simplex virus; no cases of oesophagitis
      and oesophagobrochial fistula as a result of varicella zoster virus (VZV) have
      been reported to date. This report describes the case of a patient with a 2-3 mm
      deep oesophageal ulcer whose viral culture was positive for VZV. The patient was
      treated with acyclovir with resolution of the symptomatology. After the end of
      the induction treatment, because of the onset of fever and fits of coughing
      during eating, the patient underwent oesophagography, which showed an ulcer with
      an oesophagobronchial fistula in the middle and lower third of the oesophagus.
      This case report stresses the role of VZV infection as a possible cause of
      oesophagobronchial fistula, a rare but benign condition in patients with AIDS.

PMID- 11986353
TI  - Vaccination to prevent varicella and shingles.

PMID- 11986354
TI  - Introduction to the special issue: economic, health, and mental health
      disparities among ethnic minority children and families.

PMID- 11986355
TI  - Expanding pediatric psychology beyond hospital walls to meet the health care
      needs of ethnic minority children.
AB  - OBJECTIVE: To discuss the need for an ecological model and new approaches for
      meeting the psychological and physical health care needs of minority children.
      METHOD: I support approaches that are informal, empowerment oriented, and
      culturally sensitive and that address illness prevention and health promotion.
      DISCUSSION: Assessment, intervention, and research challenges involved in
      implementing these approaches are identified, and some strategies for overcoming
      these challenges are discussed. CONCLUSIONS: Pediatric psychology can be expanded
      to embrace the advocated model and intervention approaches to better meet the
      health care needs of minority children.

PMID- 11986356
TI  - Empirically supported treatments in pediatric psychology: where is the diversity?
AB  - OBJECTIVE: To examine the extent to which studies used to support empirically
      supported treatments for asthma, cancer, diabetes, and obesity address issues of
      cultural diversity. METHOD: We chose original articles (71) of treatments used to
      support empirically supported treatments (ESTs) published as part of a special
      series on ESTs in the Journal of Pediatric Psychology. Trained coders reviewed
      each study to determine if the following were reported: race/ethnicity and
      socioeconomic status (SES) of the sample, moderating cultural variables, cultural
      assumptions or biases of the treatment, larger cultural issues, and measurement
      or procedure bias. RESULTS: Results revealed that few studies addressed cultural
      variables in any way. Only 27% of the studies reported the race or ethnicity and
      18% reported the SES of research participants. Additionally, 6% discussed
      potential moderating cultural variables. The remaining variables were addressed
      in 7% or less of the studies. CONCLUSIONS: These data support the criticism that
      ESTs fail to address important issues of culture and call into question the
      external validity of ESTs to diverse populations. Future research should
      explicitly address cultural issues according to the nine recommendations
      described here.

PMID- 11986357
TI  - Cultural issues in the treatment of young African American children diagnosed
      with disruptive behavior disorders.
AB  - OBJECTIVE: To discuss issues relevant to treating young African American children
      with disruptive behavior disorders. METHOD: We treat behavior disorders,
      correlates of behavior disorders, and special differences between African
      American and Caucasian children that could lead to or explain behavior problems.
      DISCUSSION: The majority of the information on young children diagnosed with
      disruptive behavior disorders has been obtained primarily from Caucasian children
      and families. Unfortunately, this reliance on Caucasian data neglects the unique
      needs of minorities and may lessen the quality of the services that they receive.
      Omission of ethnic concerns becomes even more salient with the increasing ethnic
      diversity among children and families in the United States. CONCLUSIONS: We
      suggest future research and clinical directions that will ultimately assist
      clinicians to provide high-quality mental health services to African American
      children.

PMID- 11986358
TI  - Validation of a screening instrument for exposure to violence in African American
      children.
AB  - OBJECTIVE: To provide concurrent validity data for the KID-SAVE as a screening
      instrument for exposure to violence in African American children, to explore
      demographic differences in KID-SAVE scores, and to provide preliminary
      reliability data on a parent version of the KID-SAVE. METHOD: Questionnaire data
      were collected regarding exposure to violence, children's behavior and symptoms,
      and family aggression. A sample of 182 children and their parents participated.
      RESULTS: Both parent and child report of violence exposure was significantly
      related to the child's psychological adjustment as endorsed by both parents and
      children. Also, significant relationships were obtained between parent report of
      their child's exposure to violence and the presence of family violence.
      CONCLUSIONS: The KID-SAVE appears to be a promising instrument for the assessment
      of exposure to violence, specifically in African American children, and may be
      applicable in a variety of clinical settings.

PMID- 11986359
TI  - Psychological distress in high-risk youth with asthma.
AB  - OBJECTIVE: To examine the relationship between asthma and psychological distress
      among adolescents already at-risk for adjustment problems secondary to lower
      economic strata and educational or vocational failure. METHOD: Twenty-five high
      risk adolescents with asthma and 25 high-risk controls without asthma 16 to 21
      years old completed the Brief Symptom Inventory, the Beck Depression Inventory,
      and the Beck Anxiety Inventory. RESULTS: Adolescents with asthma had
      significantly higher scores on multiple measures of psychological distress.
      Specifically, adolescents with asthma evidenced higher levels of anxiety,
      depression, and global psychological distress than those without asthma.
      CONCLUSIONS: High-risk adolescents with asthma may be more likely to experience
      psychological distress than those without asthma. Our findings suggest that
      asthma constitutes an additional significant independent stressor or risk factor
      among adolescents who already are at high risk for multiple adjustment problems.

PMID- 11986361
TI  - Medical management of asthma and folk medicine in a Hispanic community.
AB  - OBJECTIVE: To describe beliefs about asthma and asthma treatment in a Hispanic
      (Dominican-American) community to determine how alternative belief systems affect
      compliance with medical regimens. METHOD: Twenty-five mothers of children with
      asthma were interviewed in their homes, in their primary language, Spanish.
      Mothers were questioned about their beliefs regarding asthma etiology, treatment,
      prevention of acute episodes, and use of prescribed medications. RESULTS: Most
      mothers (72%) said that they did not use prescribed medicines for the prevention
      of asthma; instead, they substituted folk remedies called "zumos." The home
      remedies were derived from their folk beliefs about health and illness. Most
      mothers (60%) thought that their child did not have asthma in the absence of an
      acute episode. Eighty-eight percent said that medications are overused in this
      country and that physicians hide therapeutic information from them. CONCLUSIONS:
      Mothers' reliance on home remedies for asthma prevention leads to a high rate of
      noncompliance with prescribed regimens. Yet they perceive themselves as compliant
      with an effective regimen that differs from standard medical practice. Further
      studies should explore ways of promoting physician/patient communication in order
      to find ways of coordinating medical and folk beliefs to enhance compliance with
      medically prescribed regimens.

PMID- 11986360
TI  - Psychological adjustment, substance use, HIV knowledge, and risky sexual behavior
      in at-risk minority females: developmental differences during adolescence.
AB  - OBJECTIVE: To assess developmental differences in the psychological functioning,
      substance use, coping style, social support, HIV knowledge, and risky sexual
      behavior of at-risk, minority adolescent girls; to assess developmental
      differences in psychosocial correlates of risky sexual behavior in older and
      younger adolescents. METHOD: Participants included 164 minority teens, ages 12
      19, who were receiving medical care in an adolescent primary care clinic. Teens
      completed measures of psychological adjustment, substance use, coping style,
      social support, religious involvement, and HIV knowledge and attitudes. In
      addition, they answered questions regarding their sexual history, family
      situation, school status, and psychiatric and legal history. RESULTS: Younger
      teens (ages 12-15) reported more symptoms of depression and earlier sexual debuts
      than older teens (ages 16-19). However, older teens reported significantly more
      substance use and were more likely to have been pregnant and to have contracted a
      sexually transmitted disease (STD) than younger teens. Older teens also reported
      more religious involvement and using more adaptive coping strategies than younger
      teens. Developmental differences in the correlates of risky behaviors were also
      found between younger and older teens. Specifically, conduct problems and
      substance use were significantly associated with risky sexual behavior for
      younger teens, but not for older teens. Similarly, younger teens whose peers were
      engaging in risky behaviors reported engaging in more risky sexual behaviors;
      however, these same relations were not found for older teens. CONCLUSIONS: Young
      minority adolescents exhibiting conduct problems and using substances seem to be
      at highest risk for contracting HIV and STDs as a result of risky sexual
      behavior. Prevention interventions should target teens in high-risk environments
      during late elementary school or early middle school to encourage teens to delay
      intercourse, practice safer sex, and avoid drug and alcohol use. An
      interdisciplinary model of care in primary care settings is clearly indicated to
      provide these services to at-risk youths.

PMID- 11986362
TI  - Race as a moderator of parent and family outcomes following pediatric traumatic
      brain injury.
AB  - OBJECTIVE: To use data from a prospective, longitudinal study to determine
      whether race moderates parent and family outcomes during the first year following
      pediatric traumatic brain injuries (TBI). METHOD: Participants included 73 white
      and 18 black children with moderate to severe TBI and their families, and 32
      white and 23 black children with orthopedic injuries only (OI) and their
      families. Assessments of parent and family functioning occurred shortly after
      injury (baseline) and at 6- and 12-month follow-ups. RESULTS: Race was a
      significant moderator of group differences in parental psychological distress and
      perceived family burden, by and large independent of socioeconomic status. The
      negative consequences of TBI were relatively less pronounced for parents of black
      children than for parents of white children at baseline, but became more
      pronounced at the two follow-ups. Black and white parents differed in preferred
      coping strategies, which may partially account for their different reactions to
      their children's injuries. CONCLUSIONS: The sociocultural factors associated with
      race may moderate the effects of pediatric TBI and OI on parents and families.

PMID- 11986363
TI  - Cause for excite-M-ent in adrenal chromaffin cells.

PMID- 11986364
TI  - Mechanism of Kir6.2 channel inhibition by sulfhydryl modification: pore block or
      allosteric gating?
AB  - Chemical modification can inhibit ion channels either by reacting with pore
      lining residues and directly occluding the channel or by closing the channel
      allosterically. A general method to distinguish between these two mechanisms does
      not exist. Previously, sulfhydryl (SH) modification has been shown to inhibit ATP
      sensitive K(+) (K(ATP)) channels. The crucial modification has been localized to
      C42 near the N-terminus of Kir6.2, a pore-forming subunit of K(ATP) channels, but
      little is known about how SH modification of C42 causes channel inhibition. To
      investigate this mechanism, we used the membrane-impermeable
      methanethiosulfonates, MTSET and MTS-TEAH, to modify Kir6.2 channels. While
      intracellular application of MTSET irreversibly inhibited channels, MTS-TEAH
      failed to do so. Instead, MTS-TEAH treatment prolonged channel openings and
      prevented the effect of subsequent MTSET treatment. Similar observations were
      made in mutants in which cysteines other than C42 had been mutated. Neither MTSET
      nor MTS-TEAH, however, affected mutant channels in which valines were substituted
      for C42 residues in all subunits. The reagents were effective when two of four
      C42 residues in the tetramer were replaced by valines. These results can be
      interpreted as indicating that both reagents modify C42. We then employed
      spermine, a known inner pore blocker, as a probe to examine whether MTS-TEAH
      modification alters pore accessibility. We found that spermine block was not
      changed by MTS-TEAH modification. Based on these data, we postulate that C42
      faces either the cytoplasm or a vestibule section wide enough to allow spermine
      to pass freely after modification by MTS-TEAH. Our study suggests that channel
      inhibition caused by SH modification of Kir6.2 is an allosteric effect, and is
      not caused by direct pore blockage.

PMID- 11986365
TI  - Activity-dependent bidirectional regulation of GABA(A) receptor channels by the 5
      HT(4) receptor-mediated signalling in rat prefrontal cortical pyramidal neurons.
AB  - Emerging evidence has implicated a potential role for 5-HT(4) receptors in
      cognition and anxiolysis. One of the main target structures of 5-HT(4) receptors
      on 'cognitive and emotional' pathways is the prefrontal cortex (PFC). As
      GABAergic signalling plays a key role in regulating PFC functions, we examined
      the effect of 5-HT(4) receptors on GABA(A) receptor channels in PFC pyramidal
      neurons. Application of 5-HT(4) receptor agonists produced either an enhancement
      or a reduction of GABA-evoked currents in PFC neurons, which are both mediated by
      anchored protein kinase A (PKA). Although PKA phosphorylation of GABA(A) receptor
      beta3 or beta1 subunits leads to current enhancement or reduction respectively in
      heterologous expression systems, we found that beta3 and beta1 subunits are co
      expressed in PFC pyramidal neurons. Interestingly, altering PKA activation levels
      can change the direction of the dual effect, switching enhancement to reduction
      and vice versa. In addition, increased neuronal activity in PFC slices elevated
      the PKA activation level, changing the enhancing effect of 5-HT(4) receptors on
      the amplitude of GABAergic inhibitory postsynaptic currents (IPSCs) to a
      reduction. These results suggest that 5-HT(4) receptors can modulate GABAergic
      signalling bidirectionally, depending on the basal PKA activation levels that are
      determined by neuronal activity. This modulation provides a unique and flexible
      mechanism for 5-HT(4) receptors to dynamically regulate synaptic transmission and
      neuronal excitability in the PFC network.

PMID- 11986366
TI  - Roscovitine: a novel regulator of P/Q-type calcium channels and transmitter
      release in central neurons.
AB  - Roscovitine is widely used for inhibition of cdk5, a cyclin-dependent kinase
      expressed predominantly in the brain. A novel function of roscovitine, i.e. an
      effect on Ca(2+) channels and transmitter release in central neurons, was studied
      by whole-cell voltage-clamp recordings and time-lapse fluorescence imaging
      techniques. Extracellular application of roscovitine markedly enhanced the tail
      calcium current following repolarization from depolarized voltages. This effect
      was rapid, reversible and dose dependent. Roscovitine dramatically slowed the
      deactivation kinetics of calcium channels. The deactivation time constant was
      increased 3- to 6-fold, suggesting that roscovitine could prolong the channel
      open state and increase the calcium influx. The potentiation of tail calcium
      currents caused by roscovitine and by the L-channel activator Bay K 8644 was not
      occluded but additive. Roscovitine-induced potentiation of tail calcium currents
      was significantly blocked by the P/Q-channel blocker CgTx-MVIIC, indicating that
      the major target of roscovitine is the P/Q-type calcium channel. In mutant mice
      with targeted deletion of p35, a neuronal specific activator of cdk5, roscovitine
      regulated calcium currents in a manner similar to that observed in wild-type
      mice. Moreover, intracellular perfusion of roscovitine failed to modulate calcium
      currents. These results suggest that roscovitine acts on extracellular site(s) of
      calcium channels via a cdk5-independent mechanism. Roscovitine potentiated
      glutamate release at presynaptic terminals of cultured hippocampal neurons
      detected with the vesicle trafficking dye FM1-43, consistent with the positive
      effect of roscovitine on the P/Q-type calcium channel, the major mediator of
      action potential-evoked transmitter release in the mammalian CNS.

PMID- 11986367
TI  - Hypoxia inhibits human recombinant large conductance, Ca(2+)-activated K(+) (maxi
      K) channels by a mechanism which is membrane delimited and Ca(2+) sensitive.
AB  - Large conductance, Ca(2+)-activated K(+) (maxi-K ) channel activity was recorded
      in excised, inside-out patches from HEK 293 cells stably co-expressing the alpha-
      and beta-subunits of human brain maxi-K channels. At +50 mV, and in the presence
      of 300 nM Ca2+i, single channel activity was acutely and reversibly suppressed
      upon reducing P(O(2)) from 150 to > 40 mmHg by over 30 %. The hypoxia-evoked
      reduction in current was due predominantly to suppression in NP(o), although a
      minor component was attributable to reduced unitary conductance of 8-12 %.
      Hypoxia caused an approximate doubling of the time constant for activation but
      was without effect on deactivation. At lower levels of Ca2+i(30 and 100 nM),
      hypoxic inhibition did not reach significance. In contrast, 300 nM and 1 microM
      Ca2+i both sustained significant hypoxic suppression of activity over the entire
      activating voltage range. At these two Ca2+i levels, hypoxia evoked a positive
      shift in the activating voltage (by approximately 10 mV at 300 nM and
      approximately 25 mV at 1 microM). At saturating [Ca(2+)](i) (100 microM), hypoxic
      inhibition was absent. Distinguishing between hypoxia-evoked changes in voltage-
      and/or Ca2+i-sensitivity was achieved by evoking maximal channel activity using
      high depolarising potentials (up to +200 mV) in the presence of 300 nM or 100
      microM Ca2+i or in its virtual absence (> 1 nM). Under these experimental
      conditions, hypoxia caused significant channel inhibition only in the presence of
      300 nM Ca2+i. Thus, since regulation was observed in excised patches, maxi-K
      channel inhibition by hypoxia does not require soluble intracellular components
      and, mechanistically, is voltage independent and Ca2+i sensitive.

PMID- 11986368
TI  - Association of upregulated activity of K(ATP) channels with impaired insulin
      secretion in UCP1-expressing insulinoma cells.
AB  - Insulin-secreting MIN6 cells overexpressing uncoupling protein-1 (UCP1) were
      studied regarding insulin secretion in response to various secretagogues.
      Overexpression of UCP1 prevented an increase of cytosolic ATP levels induced by
      glucose. In contrast, glucose utilization was not affected, nor was glycerol
      phosphate flux. The UCP1-expressing cells showed an inability to increase
      cytosolic Ca(2+) concentration ([Ca(2+)](i)) in response to glucose or alpha
      ketoisocaproate and this resulted in less insulin secretion, whereas initial
      reduction in [Ca(2+)](i) occurring upon either nutrient addition was not
      affected. Moreover, the effectiveness of tolbutamide on [Ca(2+)](i) increase was
      reduced and the dose-response relations for insulin secretion induced by the
      agent was shifted toward the right in the UCP1-expressing cells. The resting
      membrane potential of the UCP1-expressing cells was significantly hyperpolarized
      by 6.2 mV compared with control cells. In the perforated and conventional whole
      cell patch-clamp configurations, the conductance density of ATP-sensitive K(+)
      (K(ATP)) channels of the UCP1-expressing cells was 6-fold and 1.7-fold greater
      than that of the control cells, respectively. The sensitivity of K(ATP) channels
      for tolbutamide was not different between two groups, indicating that in intact
      cells more than 6-fold higher concentrations of tolbutamide were required to
      reduce the K(ATP) channel currents of UCP1-expressing cells to the same levels as
      of the control cells. The current density of the voltage-dependent Ca(2+)
      channels was not influenced. In conclusion, UCP1-expressing cells showed a
      refractoriness to respond to tolbutamide as well as nutrients. An upregulated
      activity of K(ATP) channels was associated with unresponsiveness to the agent in
      the cells with impaired mitochondrial function.

PMID- 11986369
TI  - Adenosine inhibition via A(1) receptor of N-type Ca(2+) current and peptide
      release from isolated neurohypophysial terminals of the rat.
AB  - Effects of adenosine on voltage-gated Ca(2+) channel currents and on arginine
      vasopressin (AVP) and oxytocin (OT) release from isolated neurohypophysial (NH)
      terminals of the rat were investigated using perforated-patch clamp recordings
      and hormone-specific radioimmunoassays. Adenosine, but not adenosine 5'
      triphosphate (ATP), dose-dependently and reversibly inhibited the transient
      component of the whole-terminal Ba(2+) currents, with an IC(50) of 0.875 microM.
      Adenosine strongly inhibited, in a dose-dependent manner (IC(50) = 2.67 microM),
      depolarization-triggered AVP and OT release from isolated NH terminals. Adenosine
      and the N-type Ca(2+) channel blocker omega-conotoxin GVIA, but not other Ca(2+)
      channel-type antagonists, inhibited the same transient component of the Ba(2+)
      current. Other components such as the L-, Q- and R-type channels, however, were
      insensitive to adenosine. Similarly, only adenosine and omega-conotoxin GVIA were
      able to inhibit the same component of AVP release. A(1) receptor agonists, but
      not other purinoceptor-type agonists, inhibited the same transient component of
      the Ba(2+) current as adenosine. Furthermore, the A(1) receptor antagonist 8
      cyclopentyltheophylline (CPT), but not the A(2) receptor antagonist 3, 7-dimethyl
      1-propargylxanthine (DMPGX), reversed inhibition of this current component by
      adenosine. The inhibition of AVP and OT release also appeared to be via the A(1)
      receptor, since it was reversed by CPT. We therefore conclude that adenosine,
      acting via A(1) receptors, specifically blocks the terminal N-type Ca(2+) channel
      thus leading to inhibition of the release of both AVP and OT.

PMID- 11986370
TI  - A Ca(2+)-inhibited non-selective cation conductance contributes to pacemaker
      currents in mouse interstitial cell of Cajal.
AB  - Interstitial cells of Cajal (ICC) provide pacemaker activity in some smooth
      muscles. The nature of the pacemaker conductance is unclear, but studies suggest
      that pacemaker activity is due to a voltage-independent, Ca(2+)-regulated, non
      selective cation conductance. We investigated Ca(2+)-regulated conductances in
      murine intestinal ICC and found that reducing cytoplasmic Ca(2+) activates whole
      cell inward currents and single-channel currents. Both the whole-cell currents
      and single-channel currents reversed at 0 mV when the equilibrium potentials of
      all ions present were far from 0 mV. Recordings from on-cell patches revealed
      oscillations in unitary currents at the frequency of pacemaker currents in ICC.
      Voltage-clamping cells to -60 mV did not change the oscillatory activity of
      channels in on-cell patches. Depolarizing cells with high external K(+) caused
      loss of resolvable single-channel currents, but the oscillatory single-channel
      currents were restored when the patches were stepped to negative potentials.
      Unitary currents were also resolved in excised patches. The single-channel
      conductance was 13 pS, and currents reversed at 0 mV. The channels responsible
      were strongly activated by 10(-7) M Ca(2+), and 10(-6) M Ca(2+) reduced activity.
      The 13 pS channels were strongly activated by the calmodulin inhibitors
      calmidazolium and W-7 in on-cell and excised patches. Calmidazolium and W-7 also
      activated a persistent inward current under whole-cell conditions. Murine ICC
      express Ca(2+)-inhibited, non-selective cation channels that are periodically
      activated at the same frequency as pacemaker currents. This conductance may
      contribute to the pacemaker current and generation of electrical slow waves in GI
      muscles.

PMID- 11986371
TI  - Rapidly and slowly activating components of delayed rectifier K(+) current in
      guinea-pig sino-atrial node pacemaker cells.
AB  - The components and properties of the delayed rectifier K(+) current (I(K)) in
      isolated guinea-pig sino-atrial (SA) node pacemaker cells were investigated using
      the whole-cell configuration of the patch-clamp technique. An envelope of tails
      test was conducted by applying depolarizing pulses from a holding potential of 
      50 mV to +30 mV for various durations ranging from 40 to 2000 ms. The ratio of
      the tail current amplitude elicited upon return to the holding potential to the
      magnitude of the time-dependent outward current activated during depolarizing
      steps was dependent on the pulse duration, while after exposure to the selective
      I(Kr) inhibitor E-4031 (5 microM) this current ratio became practically constant
      irrespective of the pulse duration. These observations are consistent with the
      presence of the E-4031-sensitive, rapidly activating and E-4031-resistant, slowly
      activating components of I(K) (I(Kr) and I(Ks), respectively) in guinea-pig SA
      node cells. The activation range for I(Kr), defined as the E-4031-sensitive
      current (half-maximal activation voltage (V(1/2)) of -26.2 mV) was much more
      negative than that for I(Ks), defined as the E-4031-resistant current (V(1/2) of
      +17.2 mV). I(Kr) exhibited a marked inward rectification at potentials positive
      to -50 mV, whereas I(Ks) showed only a slight rectification. In the current-clamp
      experiments, bath application of E-4031 (0.5 and 5 microM) initially slowed the
      repolarization at potentials negative to approximately -30 mV and produced a
      significant depolarization of the maximum diastolic potential, followed by the
      arrest of electrical activity, thus indicating that the late phase of the
      repolarization leading to the maximum diastolic potential at around -60 mV in
      spontaneous action potentials is primarily produced by I(Kr) in guinea-pig SA
      node cells. External application of the selective I(Ks) inhibitor 293B (30
      microM) also delayed the repolarization process at potentials negative to about 
      20 mV and induced moderate depolarization of the maximum diastolic potential
      leading to the arrest of the spontaneous activity. These results provide evidence
      to suggest that both I(Kr) and I(Ks) are present and play crucial roles in the
      spontaneous electrical activity of guinea-pig SA node pacemaker cells.

PMID- 11986372
TI  - Inward rectifier K(+) current under physiological cytoplasmic conditions in
      guinea-pig cardiac ventricular cells.
AB  - The outward current that flows through the strong inward rectifier K(+) (K(IR))
      channel generates I(K1), one of the major repolarizing currents of the cardiac
      action potential. The amplitude and the time dependence of the outward current
      that flows through K(IR) channels is determined by its blockage by cytoplasmic
      cations such as polyamines and Mg(2+). Using the conventional whole-cell
      recording technique, we recently showed that the outward I(K1) can show a time
      dependence during repolarization due to competition of cytoplasmic particles for
      blocking K(IR) channels. We used the amphotericin B perforated patch-clamp
      technique to measure the physiological amplitude and time dependence of I(K1)
      during the membrane repolarization of guinea-pig cardiac ventricular myocytes. In
      5.4 mM K(+) Tyrode solution, the density of the current consisting mostly of the
      sustained component of the outward I(K1) was about 3.1 A F(-1) at around -60 mV.
      The outward I(K1) showed an instantaneous increase followed by a time-dependent
      decay (outward I(K1) transient) on repolarization to -60 to -20 mV subsequent to
      a 200 ms depolarizing pulse at +37 mV (a double-pulse protocol). The amplitudes
      of the transients were large when a hyperpolarizing pre-pulse was applied before
      the double-pulse protocol, whereas they were small when a depolarizing pre-pulse
      was applied. The peak amplitudes of the transients elicited using a
      hyperpolarizing pre-pulse were 0.36, 0.63 and 1.01 A F(-1), and the decay time
      constants were 44, 14 and 6 ms, at -24, -35 and -45 mV, respectively. In the
      current-clamp experiments, a phase-plane analysis revealed that application of
      pre-pulses changed the current density at the repolarization phase to the extents
      expected from the changes of the I(K1) transient. Our study provides the first
      evidence that an outward I(K1) transient flows during cardiac action potentials.

PMID- 11986373
TI  - Modulation of K(+) currents in Xenopus spinal neurons by p2y receptors: a role
      for ATP and ADP in motor pattern generation.
AB  - We have investigated the pharmacological properties and targets of p2y
      purinoceptors in Xenopus embryo spinal neurons. ATP reversibly inhibited the
      voltage-gated K(+) currents by 10 +/- 3 %. UTP and the analogues alpha,beta
      methylene-ATP and 2-methylthio-ATP also inhibited K(+) currents. This agonist
      profile is similar to that reported for a p2y receptor cloned from Xenopus
      embryos. Voltage-gated K(+) currents could be inhibited by ADP (9 +/- 0.8 %)
      suggesting that a further p2y1-like receptor is also present in the embryo spinal
      cord. Unexpectedly we found that alpha,beta-methylene-ADP, often used to block
      the ecto-5'-nucleotidase, also inhibited voltage-gated K(+) currents (7 +/- 2.3
      %). This inhibition was occluded by ADP, suggesting that alpha,beta-methylene-ADP
      is an agonist at p2y1 receptors. We have directly studied the properties of the
      ecto-5'-nucleotidase in Xenopus embryo spinal cord. Although ADP inhibited this
      enzyme, alpha,beta-methylene-ADP had no action. Caution therefore needs to be
      used when interpreting the actions of alpha,beta-methylene-ADP as it has
      previously unreported agonist activity at P2 receptors. Xenopus spinal neurons
      possess fast and slow voltage-gated K(+) currents. By using catechol to
      selectively block the fast current, we completely occluded the actions of ATP and
      ADP. Furthermore, the purines appeared to block only the fast relaxation
      component of the tail currents. We therefore conclude that the p2y receptors
      target only the fast component of the delayed rectifier. As ATP breakdown to ADP
      is rapid and ADP may accumulate at higher levels than ATP, the contribution of
      ADP acting through p2y1-like receptors may be an important additional mechanism
      for the control of spinal motor pattern generation.

PMID- 11986374
TI  - Spike-independent release of ATP from Xenopus spinal neurons evoked by activation
      of glutamate receptors.
AB  - As the release of ATP from neurons has only been directly studied in a few cases,
      we have used patch sniffing to examine ATP release from Xenopus spinal neurons.
      ATP release was detected following intracellular current injection to evoke
      spikes. However, spiking was not essential as both glutamate and NMDA could evoke
      release of ATP in the presence of TTX. Neither acetylcholine nor high K(+) was
      effective at inducing ATP release in the presence of TTX. Although Cd(2+) blocked
      glutamate-evoked release of ATP suggesting a dependence on Ca(2+) entry, neither
      omega-conotoxin-GVIA nor nifedipine prevented ATP release. N-type and L-type
      channels are thus not essential for glutamate-evoked ATP release. That glutamate
      receptors can elicit release in the absence of spiking suggests a close physical
      relationship between these receptors, the Ca(2+) channels and release sites. As
      the dependence of ATP release on the influx of Ca(2+) through Ca(2+) channel
      subtypes differs from that of synaptic transmitter release, ATP may be released
      from sites that are distinct from those of the principal transmitter. In addition
      to its role as a fast transmitter, ATP may thus be released as a consequence of
      the activation of excitatory glutamatergic synapses and act to signal information
      about activity patterns in the nervous system.

PMID- 11986375
TI  - Developmental profiles of glutamate receptors and synaptic transmission at a
      single synapse in the mouse auditory brainstem.
AB  - Using whole-cell recordings from presynaptic terminals and postsynaptic principal
      neurons in the mouse medial nucleus of the trapezoid body (MNTB), we have
      characterized properties of the calyx of Held synapse during the first three
      postnatal weeks. We observed that evoked excitatory postsynaptic currents (EPSCs)
      mediated by NMDA receptors (NMDAR) increased until postnatal day 11/12 (P11/12)
      after which they declined to very low or undetectable levels at P16. Meanwhile,
      EPSCs mediated by AMPA receptors (AMPAR) showed an approximate three-fold
      increase in amplitude. These changes were paralleled by NMDAR and AMPAR currents
      evoked by exogenous NMDA and kainate to MNTB neurons except that whole-cell
      kainate currents remained constant after P7/8 while AMPAR-EPSCs continued to
      increase. We found that the decay time constant tau for NMDAR-EPSCs and AMPAR
      EPSCs declined by about 30 % and 70 %, respectively. Analyses of NMDAR-EPSCs with
      subunit-specific pharmacological agents including ifenprodil, N,N,N',N'
      tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), zinc and Mg(2+) revealed subtle
      developmental changes in subunit composition. As maturation progressed, this
      synapse displayed a reduction in the number of presynaptic spike failures and the
      extent of synaptic depression in response to trains of stimuli (50-300 Hz) while
      the recovery rate from depression accelerated. These results demonstrate profound
      changes in the size and kinetics of postsynaptic glutamate receptors and in the
      spike-firing capability of presynaptic terminals at the calyx of Held-MNTB
      synapse during early development. We suggest that these concurrent presynaptic
      and postsynaptic adaptations represent important steps for synapse consolidation
      and refinement and ultimately for the development of fast high-fidelity
      transmission at this synapse.

PMID- 11986376
TI  - An M-like outward current regulates the excitability of spinal motoneurones in
      the adult turtle.
AB  - The excitatory action of muscarine on spinal motoneurones was investigated with
      intracellular recordings in a slice preparation from adult turtles. In these
      cells muscarine is known to facilitate a persistent inward current mediated by L
      type Ca(2+) channels. When this effect was blocked by nifedipine, muscarine still
      increased the excitability. In voltage clamp, a slowly activating outward
      current, generated during depolarizing voltage commands and deactivating as a
      tail current on return to the holding voltage, was reduced by muscarine. This
      outward current was activated when the voltage was stepped to potentials positive
      to -60 mV, was voltage sensitive and had a deactivation time constant of
      approximately 80 ms. These findings are compatible with an M-current. This
      possibility was also supported by the finding that the current was reduced by XE
      991 - a selective blocker of the KCNQ potassium channels underlying M-currents in
      other cell types. Our findings suggest that an M-like current, mediated by a KCNQ
      channel, contributes to the intrinsic response properties of motoneurones in the
      adult spinal cord by increasing adaptation of repetitive firing and decreasing
      the slope of the frequency-current relation.

PMID- 11986377
TI  - Phosphorylation and functional regulation of ClC-2 chloride channels expressed in
      Xenopus oocytes by M cyclin-dependent protein kinase.
AB  - Many dramatic alterations in various cellular processes during the cell cycle are
      known to involve ion channels. In ascidian embryos and Caenorhabditis elegans
      oocytes, for example, the activity of inwardly rectifying Cl(-) channels is
      enhanced during the M phase of the cell cycle, but the mechanism underlying this
      change remains to be established. We show here that the volume-sensitive Cl(-)
      channel, ClC-2 is regulated by the M-phase-specific cyclin-dependent kinase,
      p34(cdc2)/cyclin B. ClC-2 channels were phosphorylated by p34(cdc2)/cyclin B in
      both in vitro and cell-free phosphorylation assays. ClC-2 phosphorylation was
      inhibited by olomoucine and abolished by a (632)Ser-to-Ala (S632A) mutation in
      the C-terminus, indicating that (632)Ser is a target of phosphorylation by
      p34(cdc2)/cyclin B. Injection of activated p34(cdc2)/cyclin B attenuated the ClC
      2 currents but not the S632A mutant channel currents expressed in Xenopus
      oocytes. ClC-2 currents attenuated by p34(cdc2)/cyclin B were increased by
      application of the cyclin-dependent kinase inhibitor, olomoucine (100 microM), an
      effect that was inhibited by calyculin A (5 nM) but not by okadaic acid (5 nM). A
      yeast two-hybrid system revealed a direct interaction between the ClC-2 C
      terminus and protein phosphatase 1. These data suggest that the ClC-2 channel is
      also counter-regulated by protein phosphatase 1. In addition, p34(cdc2)/cyclin B
      decreased the magnitude of ClC-2 channel activation caused by cell swelling. As
      the activities of both p34(cdc2)/cyclin B and protein phosphatase 1 vary during
      the cell cycle, as does cell volume, the ClC-2 channel could be regulated
      physiologically by these factors.

PMID- 11986378
TI  - Mechanisms and physiological role of enhancement of mGlu5 receptor function by
      group II mGlu receptor activation in rat perirhinal cortex.
AB  - In this study we have investigated mechanisms underlying enhancement by group II
      metabotropic glutamate (mGlu) receptors of group I mGlu receptor-induced calcium
      mobilization. Inhibition of protein kinase A (PKA) caused an enhancement of mGlu5
      receptor-mediated calcium mobilization and occluded the enhancement by group II
      mGlu receptors. A peptide (Ht31) that prevents interaction between A-kinase
      anchoring protein (AKAP) and PKA also enhanced mGlu5-mediated calcium
      mobilization. Enhancement of mGlu5 function, by inhibition of PKA or by
      activation of group II mGlu receptors, was prevented by the protein phosphatase
      2B (PP2B) inhibitor cyclosporin A. Furthermore, the enhancement by activation of
      group II mGlu receptors was prevented by raising intracellular cAMP. These
      results suggest that the regulation by PKA and PP2B of phosphorylation of a
      substrate on mGlu5 and/or on group II mGlu receptors is intimately involved in
      the mechanisms underlying interaction between group II mGlu and mGlu5 receptors.
      Long-term depression (LTD) in perirhinal cortex requires group I, group II and
      NMDA receptor activation at resting membrane potentials but does not require
      group II mGlu receptor activation at depolarized potentials. We previously
      suggested that interaction between group I and group II mGlu receptors is
      required for induction of LTD at resting potentials. In support of this, we
      demonstrate in perirhinal cortex slices that blocking mechanisms underlying mGlu
      receptor synergy (by raising intracellular cAMP or by inhibition of PP2B)
      selectively prevented LTD at resting membrane potentials. This study thus
      provides a potential explanation for the co-requirement in LTD of group I and
      group II mGlu receptor activation. Similar mechanisms of synergistic interaction
      may also be important in other physiological processes dependent on mGlu
      receptors.

PMID- 11986379
TI  - Regenerative component of slow waves in the guinea-pig gastric antrum involves a
      delayed increase in [Ca(2+)](i) and Cl(-) channels.
AB  - Regenerative potentials were initiated by depolarizing short segments of single
      bundles of circular muscle isolated from the gastric antrum of guinea-pigs. When
      changes in [Ca(2+)](i) and membrane potential were recorded simultaneously,
      regenerative potentials were found to be associated with an increase in
      [Ca(2+)](i), with the increase starting after a minimum latency of about 1 s.
      Although the increase in [Ca(2+)](i) was reduced by nifedipine, the amplitudes of
      the regenerative responses were little changed. Regenerative responses and
      associated changes in [Ca(2+)](i) were abolished by loading the preparations with
      the Ca(2+) chelator MAPTA-AM. Regenerative potentials were abolished by 2
      aminoethoxydiphenyl borate (2APB), an inhibitor of IP(3) induced Ca(2+) release,
      by N-ethylamaleimide (NEM), an alkylating agent which blocks activation of G
      proteins and were reduced in amplitude by two agents which block chloride (Cl(-))
      selective channels in many tissues. The observations suggest that membrane
      depolarization triggers IP(3) formation. This causes Ca(2+) release from
      intracellular stores which activates Ca(2+)-dependent Cl(-) channels.

PMID- 11986380
TI  - Histamine promotes excitability in bovine adrenal chromaffin cells by inhibiting
      an M-current.
AB  - The current study has investigated the electrophysiological responses evoked by
      histamine in bovine adrenal chromaffin cells using perforated-patch techniques.
      Histamine caused a transient hyperpolarization followed by a sustained
      depolarization of 7.2 +/- 1.4 mV associated with an increase in spontaneous
      action potential frequency. The hyperpolarization was abolished after depleting
      intracellular Ca(2+) stores with thapsigargin (100 nM), and was reduced by 40 %
      with apamin (100 nM). Membrane resistance increased by about 60 % during the
      histamine-induced depolarization suggesting inhibition of a K(+) channel. An
      inward current relaxation, typical of an M-current, was observed in response to
      negative voltage steps from a holding potential of -30 mV. This current reversed
      at -81.6 +/- 1.8 mV and was abolished by the M-channel inhibitor linopirdine (100
      microM). During application of histamine, the amplitude of M-currents recorded at
      a time corresponding with the sustained depolarization was reduced by 40 %. No
      inward current rectification was observed in the range -150 to -70 mV, and
      glibenclamide (10 microM) had no effect on either resting membrane potential or
      the response to histamine. The results show that an M-current is present in
      bovine chromaffin cells and that this current is inhibited during sustained
      application of histamine, resulting in membrane depolarization and increased
      discharge of action potentials. These results demonstrate for the first time a
      possible mechanism coupling histamine receptors to activation of voltage-operated
      Ca(2+) channels in these cells.

PMID- 11986381
TI  - Mechanical function of intermediate filaments in arteries of different size
      examined using desmin deficient mice.
AB  - Protein composition and mechanical function of intermediate filaments were
      examined in arteries of different sizes using desmin deficient mice (Des-/-) and
      their wild-type controls (Des+/+). Using SDS-PAGE gels and Western blots we found
      a gradient in desmin expression in the arterial tree; the desmin content
      increased from the elastic artery aorta, via the muscular mesenteric artery to
      the resistance-sized mesenteric microarteries approximately 150 microm in
      diameter in Des+/+ mice. Mechanical experiments were performed on the aorta, the
      mesenteric artery and resistance-sized arteries using wire myographs. For aorta
      and mesenteric artery, no differences in passive or active circumference- stress
      relations were found between Des-/- and Des+/+ mice. In microarteries, both
      passive and active stress were lower in the Des-/- group. In conclusion, large
      elastic and muscular arteries contain a relatively low amount of desmin, and the
      desmin intermediate filaments do not seem to play a major role in the mechanical
      properties of these larger arterial vessels. In the microarteries, where
      expression of desmin is high, desmin plays a role in supporting both passive and
      active tension.

PMID- 11986382
TI  - Quantification of the response of rat medullary raphe neurones to independent
      changes in pH(o) and P(CO2).
AB  - The medullary raphe nuclei contain putative central respiratory chemoreceptor
      neurones that are highly sensitive to acidosis. To define the primary stimulus
      for chemosensitivity in these neurones, the response to hypercapnic acidosis was
      quantified and compared with the response to independent changes in P(CO2) and
      extracellular pH (pH(o)). Neurones from the ventromedial medulla of neonatal rats
      (P0-P2) were dissociated and maintained in tissue culture for long enough to
      develop a mature response (up to 70 days). Perforated patch clamp recordings were
      used to record membrane potential and firing rate while changes were made in
      pH(o), P(CO2) and/or [NaHCO(3)](o) from baseline values of 7.4, 5 % and 26 mM,
      respectively. Hypercapnic acidosis (P(CO2) 9 %; pH(o) 7.17) induced an increase
      in firing rate to 285 % of control in one subset of neurones ('stimulated
      neurones') and induced a decrease in firing rate to 21 % of control in a
      different subset of neurones ('inhibited neurones'). Isocapnic acidosis (pH(o)
      7.16; [NaHCO(3)](o) 15 mM) induced an increase in firing rate of stimulated
      neurones to 309 % of control, and a decrease in firing rate of inhibited neurones
      to 38 % of control. In a different group of neurones, isohydric hypercapnia (9 %
      P(CO2); [NaHCO(3)](o) 40 mM) induced an increase in firing rate of stimulated
      neurones by the same amount (to 384 % of control) as in response to hypercapnic
      acidosis (to 327 % of control). Inhibited neurones also responded to isohydric
      hypercapnia in the same way as they did to hypercapnic acidosis. In Hepes
      buffered solution, both types of neurone responded to changes in pH(o) in the
      same way as they responded to changes in pH(o) in bicarbonate-buffered Ringer
      solution. It has previously been shown that all acidosis-stimulated neurones in
      the medullary raphe are immunoreactive for tryptophan hydroxylase (TpOH-ir). Here
      it was found that TpOH-ir neurones in the medullary raphe were immunoreactive for
      carbonic anhydrase type II and type IV (CA II and CA IV). However, CA
      immunoreactivity was also common in neurones of the hypoglossal motor nucleus,
      inferior olive, hippocampus and cerebellum, indicating that its presence is not
      uniquely associated with chemosensitive neurones. In addition, under the
      conditions used here, acetazolamide (100 microM) did not have a significant
      effect on the response to hypercapnic acidosis. We conclude that chemosensitivity
      of raphe neurones can occur independently of changes in pH(o), P(CO2) or
      bicarbonate. The results suggest that a change in intracellular pH (pH(i)) may be
      the primary stimulus for chemosensitivity in these putative central respiratory
      chemoreceptor neurones.

PMID- 11986383
TI  - The elementary force generation process probed by temperature and length
      perturbations in muscle fibres from the rabbit.
AB  - Single chemically permeabilized fibres from rabbit psoas muscle were activated
      maximally at 5-6 degrees C and then exposed to a rapid temperature increase ('T
      jump') up to 37 degrees C by passing a high-voltage pulse (40 kHz AC, 0.15 ms
      duration) through the fibre length. Fibre cooling after the T-jump was
      compensated by applying a warming (40 kHz AC, 200 ms) pulse. Tension and changes
      in sarcomere length induced by the T-jumps and by fast length step perturbations
      of the fibres were monitored. In some experiments sarcomere length feedback
      control was used. After T-jumps tension increased from approximately 55 kN m(-2)
      at 5-6 degrees C to approximately 270 kN m(-2) at 36-37 degrees C, while
      stiffness rose by approximately 15 %, suggesting that at a higher temperature the
      myosin head generates more force. The temperature-tension relation became less
      steep at temperatures above 25 degrees C, but was not saturated even at near
      physiological temperature. Comparison of tension transients induced by the T-jump
      and length steps showed that they are different. The T-jump transients were
      several times slower than fast partial tension recovery following length steps at
      low and high temperature (phase 2). The kinetics of the tension rise after the T
      jumps was independent of the preceding length changes. When the length steps were
      applied during the tension rise induced by the T-jump, the observed complex
      tension transient was simply the sum of two separate responses to the mechanical
      and temperature perturbations. This demonstrates the absence of interaction
      between these processes. The data suggest that tension transients induced by the
      T-jumps and length steps are caused by different processes in myosin cross
      bridges.

PMID- 11986384
TI  - Calcitonin gene-related peptide immunoreactivity and afferent receptive
      properties of dorsal root ganglion neurones in guinea-pigs.
AB  - To establish the afferent receptive properties of lumbosacral dorsal root
      ganglion (DRG) neurones that express calcitonin gene-related peptide (CGRP),
      intracellular recordings were made with fluorescent dye-filled electrodes in
      deeply anaesthetised young guinea-pigs. After determination of neuronal
      functional properties, dye was injected into the soma. CGRP-like immunoreactivity
      (CGRP-LI) was examined on histological sections of dye-marked neurones. Fourteen
      of 34 C-fibre neurones showed CGRP-LI. These included 10/21 C-fibre nociceptive
      neurones. All C-polymodal nociceptors in glabrous (n = 4) but none in hairy skin
      (n = 4) were positive. Positive C-fibre high threshold mechanoreceptive (HTM)
      units had receptive fields in dermal or deeper tissue. Four (n = 6) unresponsive
      or unidentified C-fibre units were positive. Neither C-fibre cooling sensitive (n
      = 4) nor C-fibre low threshold mechanoreceptive (LTM) units (n = 3) had CGRP-LI.
      Six of 23 A-fibre nociceptive cells were positive including one Aalpha/beta unit.
      Three of these positive cells had epidermal and three had dermal/deep receptive
      fields. Three of 36 A-fibre LTM units exhibited CGRP-LI; all were Aalpha/beta
      fibre G hair units. All glabrous skin and muscle spindle units and in hairy skin
      slowly adapting and field units, and some G-hair units lacked CGRP-LI. CGRP-LI
      stained fibres were found in tissues containing receptive fields of positive DRG
      neurones: glabrous skin, near hair follicles and in skeletal muscle. A few
      substance P-labelled neurones did not exhibit CGRP-LI and vice versa. Thus CGRP
      expression was detected in under half the nociceptive neurones, was not limited
      to nociceptive neurones and apart from receptive properties was also related to
      location/depth in the tissues of a DRG neurone's peripheral terminals.

PMID- 11986385
TI  - Regional variation in contribution of myenteric and intramuscular interstitial
      cells of Cajal to generation of slow waves in mouse gastric antrum.
AB  - When intracellular recordings were made from the antral region of murine stomach,
      cells with three different patterns of electrical activity were detected. One
      group of cells generated follower potentials, the second group generated
      pacemaker potentials and the third group generated slow waves that consisted of
      primary and secondary components. Slow waves recorded in different regions of the
      gastric antrum had similar amplitudes but different characteristic shapes. At the
      greater curvature, slow waves had large initial components. Midway between the
      greater and lesser curvature, the amplitude of the initial component was reduced
      and at the lesser curvature an initial component was difficult to detect. When
      the distributions of myenteric (ICC-MY) and intramuscular interstitial cells of
      Cajal (ICC-IM) were determined, using an antibody to Kit, ICC-MY were found to be
      present at the greater curvature but were greatly reduced in density at the
      lesser curvature. In contrast, ICC-IM were found in the circular layer of each
      region. When recordings were made from the antrum of W/W(V) mice, which lack ICC
      IM, incomplete slow waves were detected and their amplitudes fell from the
      greater to the lesser curvature. Again, a corresponding fall in the density of
      ICC-MY was detected. The observations indicate that the contribution of ICC-MY
      and ICC-IM to the generation of slow waves varies in different regions of the
      mouse gastric antrum.

PMID- 11986386
TI  - Inhibition of haem oxygenase activity increases leukocyte accumulation in the
      liver following limb ischaemia-reperfusion in mice.
AB  - The role of haem oxygenase (HO) in the hepatic accumulation of leukocytes in mice
      during the initiation of remote organ injury following normotensive limb
      ischaemia-reperfusion (I-R) was investigated. Remote organ injury was initiated
      by 1 h bilateral hindlimb ischaemia followed by either 1 or 1.5 h reperfusion (I
      R) in male C57BL/6 mice. Mice were randomly assigned to either sham (no I-R, n =
      4), I-R (n = 4 for both time points), I-R plus chromium mesoporphyrin (CrMP, n =
      4) to inhibit HO or I-R plus haemin (n = 4) to increase HO. Leukocyte
      accumulation and leukocyte-endothelial interaction were directly measured using
      fluorescence intravital microscopy. Leukocytes were labelled via an injection of
      rhodamine 6G. In sinusoids the total number and the number of stationary
      leukocytes were assessed. In postsinusoidal venules the number of adherent and
      rolling leukocytes and the velocities of both red blood cells and leukocytes were
      measured. The total number of leukocytes increased in sinusoids of I-R mice
      reaching a plateau within 1 h compared with sham animals, while the number of
      stationary leukocytes progressively increased over the entire study period.
      Stationary leukocytes in sinusoids increased after 1 and 1.5 h of I-R following
      CrMP, while they were significantly reduced following haemin treatment compared
      to animals treated with I-R only. In postsinusoidal venules a progressive
      increase in adherent leukocytes also occurred. As observed in sinusoids, CrMP
      significantly increased, while haemin significantly reduced leukocyte adhesion.
      The number of rolling leukocytes increased after CrMP in both I-R groups (1 and
      1.5 h). The velocities of rolling leukocytes declined following 1.5 h of I-R
      compared with sham. Haemin treatment of 1.5 h I-R animals restored the velocities
      back to sham levels. The calculated wall shear rates in postsinusoidal venules
      were significantly lower in all I-R groups in comparison to sham animals.
      Combination of 1.5 h I-R with CrMP resulted in the lowest shear rates of all I-R
      groups. The number of stationary leukocytes within sinusoids and adherent
      leukocytes in postsinusoidal venules were correlated to the corresponding alanine
      aminotransferase (ALT) levels. In conclusion, endogenous HO reduces leukocyte
      endothelial interactions within the liver. Thus, endogenous HO activity provides
      an important mechanism controlling the hepatic inflammatory response during the
      initiation of remote organ injury following normotensive limb ischaemia
      reperfusion.

PMID- 11986387
TI  - Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and
      thoracic duct.
AB  - There are only a few reports of the influence of imposed flow on an active lymph
      pump under conditions of controlled intraluminal pressure. Thus, the mechanisms
      are not clearly defined. Rat mesenteric lymphatics and thoracic ducts were
      isolated, cannulated and pressurized. Input and output pressures were adjusted to
      impose various flows. Lymphatic systolic and diastolic diameters were measured
      and used to determine contraction frequency and pump flow indices. Imposed flow
      inhibited the active lymph pump in both mesenteric lymphatics and in the thoracic
      duct. The active pump of the thoracic duct appeared more sensitive to flow than
      did the active pump of the mesenteric lymphatics. Imposed flow reduced the
      frequency and amplitude of the contractions and accordingly the active pump flow.
      Flow-induced inhibition of the active lymph pump followed two temporal patterns.
      The first pattern was a rapidly developing inhibition of contraction frequency.
      Upon imposition of flow, the contraction frequency immediately fell and then
      partially recovered over time during continued flow. This effect was dependent on
      the magnitude of imposed flow, but did not depend on the direction of flow. The
      effect also depended upon the rate of change in the direction of flow. The second
      pattern was a slowly developing reduction of the amplitude of the lymphatic
      contractions, which increased over time during continued flow. The inhibition of
      contraction amplitude was dependent on the direction of the imposed flow, but
      independent of the magnitude of flow. Nitric oxide was partly but not completely
      responsible for the influence of flow on the mesenteric lymph pump. Exposure to
      NO mimicked the effects of flow, and inhibition of the NO synthase by N (G)
      monomethyl-L-arginine attenuated but did not completely abolish the effects of
      flow.

PMID- 11986388
TI  - Hypertonic fluids are secreted by medial and lateral segments in duck (Anas
      platyrhynchos) nasal salt glands.
AB  - Indwelling catheters were used to collect fluid directly from the medial and
      lateral segments of duck nasal salt glands showing, for the first time, that the
      secretions are fully hypertonic before reaching the medial and lateral drainage
      ducts. Using this method it was possible to show that (a) there is a functional
      symmetry between the left and right salt glands, (b) the medial segment always
      secretes fluid at approximately twice the rate of the lateral segment and (c)
      fluid secreted by the medial segment has the same ionic composition but variable
      ion concentrations when compared with fluid from the lateral segment. A 12 %
      increase in post-segmental fluid osmolality was probably due to the evaporation
      of water from epithelial surfaces in the nasal cavities during breathing. A post
      segmental outflux of Ca(2+), Mg(2+) and Cl(-) in the medial and lateral
      collecting ducts and/or nasal epithelium may be of adaptive significance when
      birds inhabit calcium- and magnesium-rich marine environments.

PMID- 11986389
TI  - Swallowing-related activities of respiratory and non-respiratory neurons in the
      nucleus of solitary tract in the rat.
AB  - Swallowing-related activity was examined in respiratory (n = 60) and non
      respiratory (n = 82) neurons that were located in and around the nucleus of the
      solitary tract (NTS) in decerebrated, neuromuscularly blocked and artificially
      ventilated rats. Neurons that were orthodromically activated by electrical
      stimulation of the superior laryngeal nerve (SLN) were identified, and fictive
      swallowing was evoked by SLN stimulation. The pharyngeal phase of swallowing was
      monitored by hypoglossal nerve activity. Two types of non-respiratory neurons
      with swallowing-related bursts were identified: 'early' swallowing neurons (n =
      24) fired during periods of hypoglossal bursts, and 'late' swallowing neurons (n
      = 8) fired after the end of hypoglossal bursts. The remaining non-respiratory
      neurons were either suppressed (n = 21) or showed no change in activity (n = 29)
      during swallowing. On the other hand, respiratory neurons with SLN inputs
      included 56 inspiratory and four expiratory neurons. Inspiratory neurons were
      classified into two major types: a group of neurons discharged simultaneously
      with hypoglossal bursts (type 1 neurons, n = 19), while others were silent during
      bursts but were active during inter-hypoglossal bursts when swallowing was
      provoked repetitively (type 2 neurons, n = 34). Three of the expiratory neurons
      fired during hypoglossal bursts. Many of the swallowing-related non-respiratory
      neurons and the majority of the inspiratory neurons received presumed
      monosynaptic inputs from the SLN. Details of the distribution and firing patterns
      of these NTS neurons, which have been revealed for the first time in a fictive
      swallowing preparation in the rat, suggest their participation in the initiation,
      pattern formation and mutual inhibition between swallowing and respiration.

PMID- 11986390
TI  - Common principles of sensory encoding in spinal reflex modules and cerebellar
      climbing fibres.
AB  - An important step towards understanding the function of olivo-cerebellar climbing
      fibres must be to clarify what they signal. We suggest that climbing fibres
      projecting to paravermal cerebellum mediate highly integrated sensorimotor
      information derived from activity in spinal withdrawal reflex modules acting on
      single forelimb muscles. To test this hypothesis, cutaneous nociceptive receptive
      fields of spinal reflex modules were mapped and compared to those of climbing
      fibres. Quantitative methods were used both for mapping and for comparing
      receptive fields. The organization of muscle afferent input converging on
      individual climbing fibres was analysed in the light of results from receptive
      field comparisons. Individual cutaneous receptive fields in the two systems were
      readily matched. Matched pairs were highly similar with regard to detailed
      distributions of sensitivity: correlation coefficient r = 0.85; overlap of
      receptive field foci 72 % (average values). The olivary targets of muscle
      afferents from a given muscle were mainly climbing fibres with cutaneous
      receptive fields similar to that of the muscle itself, but to a lesser extent
      also other climbing fibres. In conclusion, paravermal climbing fibres apparently
      convey information integrating (i) cutaneous input to an individual spinal
      withdrawal reflex module, (ii) muscle afferent input from the output muscle of
      that module and (iii) muscle afferent input from muscles that constitute the
      output of functionally related modules. This suggests that an individual climbing
      fibre signals cutaneous sensory events reflecting activity of a single muscle
      conditional upon the functional state of the muscle itself and that of
      functionally related muscles.

PMID- 11986391
TI  - Repeated ischaemic isometric exercise increases muscle fibre conduction velocity
      in humans: involvement of Na(+)-K(+)-ATPase.
AB  - This study was performed to test two hypotheses: (1) ischaemic preconditioning
      (development of tolerance to ischaemia) influences muscle fibre conduction
      velocity (MFCV) during repeated ischaemic isometric exercise and (2) the increase
      in MFCV to supranormal levels during recovery from ischaemic exercise is caused
      by activation of Na(+)-K(+)-ATPase. For this purpose, MFCV was measured with
      surface electromyography (sEMG) during repeated ischaemic isometric exercise of
      the brachioradial muscle (2 min at 30 % of maximal voluntary contraction). The
      involvement of ischaemic preconditioning was tested by changing the duration of
      ischaemia and by intra-arterial infusion of adenosine (brachial artery, 50 microg
      min(-1) dl(-1)). The role of Na(+)-K(+)-ATPase was explored using ouabain (0.2
      microg min(-1) dl(-1)). During the exercise, MFCV decreased from 4.4 +/- 0.2 m s(
      1) to 3.7 +/- 0.2 m s(-1) (P < 0.01, n = 13). Similar reductions in MFCV were
      observed during repeated exercise, irrespective of the reperfusion time (10 min
      vs. 18 min) or duration of the ischaemia (2 vs. 10 min). However, initial MFCV
      gradually increased for each subsequent contraction when contractions were
      repeated at 10 min intervals (4.4 +/- 0.2 m s(-1) vs. 4.9 +/- 0.2 m s(-1) for the
      first and fourth contraction respectively; P < 0.01; n = 13). This increase was
      not observed when contractions were performed at 18 min intervals, nor when
      additional ischaemia was applied. Intra-arterial adenosine did not affect MFCV.
      Intra-arterial ouabain did not affect the reduction in MFCV during exercise but
      completely prevented the increase in MFCV during recovery: from 4.7 +/- 0.2 m s(
      1) to 5.2 +/- 0.2 m s(-1) vs. 4.5 +/- 0.1 m s(-1) to 4.5 +/- 0.1 m s(-1) in the
      absence and presence of ouabain respectively (P < 0.05 for ouabain effect; n =
      6). In conclusion, ischaemic preconditioning is not involved in changes in MFCV
      during repeated ischaemic isometric exercise. The increase in MFCV during
      recovery from repeated ischaemic isometric exercise is caused by rapid activation
      of Na(+)-K(+)-ATPase.

PMID- 11986392
TI  - Exercise with low muscle glycogen augments TCA cycle anaplerosis but impairs
      oxidative energy provision in humans.
AB  - We tested the hypotheses that: (i) exercise with low muscle glycogen would reduce
      pyruvate flux through the alanine aminotransferase (AAT) reaction and attenuate
      the increase in tricarboxylic acid (TCA) cycle intermediates, and (ii)
      attenuation of tricarboxylic acid cycle intermediate (TCAI) pool expansion would
      limit TCA cycle flux, thereby accelerating phosphocreatine (PCr) degradation.
      Eight men cycled for 10 min at 70 % of their (VO(2,max) on two occasions: (i)
      following their normal diet (CON) and (ii) after cycling to exhaustion and
      consuming a low carbohydrate diet for approximately 2 days (LG). Biopsies (m.
      vastus lateralis) confirmed that [glycogen] was lower in LG vs. CON at rest (257
      +/- 18 vs. 611 +/- 54 mmol (kg dry mass)(-1); P 0.05); however, net
      glycogenolysis was not different after 1 or 10 min of exercise. PCr degradation
      from rest to 1 min was approximately 26 % higher in LG vs. CON (38 +/- 4 vs. 28
      +/- 4 mmol (kg dry mass)(-1); P< or =0.05). The sum of five measured TCAIs
      (approximately 90 % of total pool) was not different between trials at rest and
      after 1 min, but was higher after 10 min in LG vs. CON (5.51 +/- 0.43 vs. 4.45 +/
      0.49 mmol (kg dry mass)(-1); P 0.05). Pyruvate dehydrogenase complex (PDC)
      activity was lower during exercise in LG vs. CON (2.2 +/- 0.2 vs. 1.4 +/- 0.2
      mmol min(-1) (kg wet weight)(-1) after 10 min; P< or =0.05), and acetylcarnitine
      was approximately threefold less, implying increased pyruvate availability for
      flux through AAT. Resting muscle [glutamate] was higher in LG vs. CON (16.1 +/-
      0.8 vs. 11.8 +/- 0.4 mmol (kg dry mass)(-1); P< or =0.05) and the net decrease in
      [glutamate] during exercise was approximately 30 % greater in LG vs. CON. These
      findings suggest that: (i) contrary to our hypotheses, LG increased anaplerosis
      by decreasing PDC flux and/or increasing the conversion of glutamate carbon to
      TCAIs, and (ii) accelerating the rate of muscle TCAI expansion did not affect
      oxidative energy provision during the initial phase of contraction, since changes
      in [TCAI] were not temporally related to PCr degradation.

PMID- 11986393
TI  - Effects of insulin on adipose tissue blood flow in man.
AB  - Adipose tissue blood flow (ATBF) rises after nutrient ingestion. It is not clear
      whether this is due to insulin. The aim of this study was to investigate the role
      of insulin in the regulation of subcutaneous ATBF. We have investigated the role
      of insulin in the regulation of ATBF in normal, healthy subjects in a three-step
      procedure to determine the functional level at which insulin may potentially
      exert its effect. Fifteen subjects were studied on two occasions. On the first
      visit, 75 g oral glucose was given. In the second, similar plasma concentrations
      of insulin and glucose were achieved by dynamic intravenous infusions of insulin
      and glucose. The increase in ATBF after oral glucose (4.2 +/- 1.4 ml min(-1) (100
      g tissue)(-1), P = 0.01) was significantly greater (P < 0.05) than that after
      intravenous infusions (1.5 +/- 0.6 ml min(-1) (100 g tissue)(-1) P < 0.05). For
      the local delivery of potentially vasoactive substances and simultaneous
      measurement of ATBF, we describe a novel combination of methods, which we have
      called 'microinfusion'. We have used this technique to show that locally infused
      insulin, even at pharmacological concentrations, had no demonstrable effect on
      ATBF in nine subjects. We conclude that whilst insulin does not have a direct
      effect on ATBF, it is likely to be an important mediator, possibly acting via
      sympathetic activation. In the postprandial state, other candidate peptides and
      hormones are also likely to play important roles.

PMID- 11986394
TI  - Heart rate at the onset of muscle contraction and during passive muscle stretch
      in humans: a role for mechanoreceptors.
AB  - Previous evidence suggests that the heart rate (HR) increase observed with
      isometric exercise is dependent on different afferent mechanisms to those
      eliciting the increase in blood pressure (BP). Central command and muscle
      metaboreceptors have been shown to contribute to this differential effect.
      However, in experimental animals passive stretch of the hindlimb increases HR
      suggesting that small fibre mechanoreceptors could also have a role. This has not
      been previously shown in humans and was investigated in this study. Healthy human
      volunteers were instrumented to record BP, ECG, respiration, EMG of rectus
      femoris and gastrocnemius and contraction force of triceps surae. Voluntary
      isometric contraction of triceps surae elicited a significant HR change in the
      first three respiratory cycles at 40 % of maximum voluntary contraction whereas
      BP did not change significantly until after 30 s. This suggests that different
      mechanisms are involved in the initiation of the cardiovascular changes.
      Sustained passive stretch of triceps surae for 1 min, by dorsiflexion of the
      foot, caused a significant (P < 0.05) increase in HR (5 +/- 2.6 beats min(-1))
      with no significant change in BP. A time domain measure of cardiac vagal activity
      was reduced significantly during passive stretch from 69.7 +/- 12.9 to 49.6 +/-
      8.9 ms. Rapid rhythmic passive stretch (0.5 Hz for 1 min) was without significant
      effect suggesting that large muscle proprioreceptors are not involved. We
      conclude that in man small fibre muscle mechanoreceptors responding to stretch,
      inhibit cardiac vagal activity and thus increase HR. These afferents could
      contribute to the initial cardiac acceleration in response to muscle contraction.

PMID- 11986395
TI  - Post-junctional alpha-adrenoceptors and basal limb vascular tone in healthy men.
AB  - Previous studies have demonstrated that post-junctional alpha(1)- and alpha(2)
      adrenoceptors mediate vasoconstriction in the human forearm. However, the
      relative contributions of the alpha-adrenoceptor subtypes to basal limb vascular
      tone are unknown. In healthy young men, forearm blood flow (FBF; venous occlusion
      plethysmography) responses to brachial artery administration of prazosin (an
      alpha(1)-adrenoceptor antagonist), yohimbine (an alpha(2)-adrenoceptor
      antagonist) and phentolamine (a non-selective alpha-adrenoceptor antagonist) were
      determined after local beta-adrenoceptor blockade with propranolol. In 10
      subjects, prazosin increased FBF from 2.4 +/- 0.3 to 5.8 +/- 1.0 ml (100 ml)(-1)
      min(-1) (approximately 140 %; P < 0.001 vs. baseline). Subsequently, phentolamine
      further increased FBF to 11.7 +/- 1.6 ml (100 ml)(-1) min(-1) (approximately 385
      %; P < 0.001 vs. baseline). Thus, the average calculated increase in FBF due to
      removal of alpha(2)-vasoconstrictor tone was greater than that due to removal of
      alpha(1)-tone (5.9 +/- 0.8 vs. 3.4 +/- 0.8 ml (100 ml)(-1) min(-1); P < 0.01) and
      represented approximately 63 % of basal sympathetic tone. Complete alpha(1)
      adrenoceptor blockade was confirmed by a minimal reduction in FBF in response to
      phenylephrine after prazosin (46 +/- 3 vs. 6 +/- 4 %; before vs. after blockade)
      and in a separate group of four subjects, increasing the dose of prazosin
      threefold did not evoke further forearm vasodilatation. Additionally, the
      reduction in FBF in response to tryamine (evokes endogenous noradrenaline
      release) was abolished after phentolamine (40 +/- 3 vs. 2 +/- 1 %; before vs.
      after blockade), documenting complete pharmacological sympathectomy. In another
      group of seven subjects, administering yohimbine prior to phentolamine resulted
      in similar findings. These observations indicate that vasoconstricting post
      junctional alpha(2)-adrenoceptors contribute more to basal vascular tone than
      alpha(1)-adrenoceptors in the forearms of young healthy men. The potential
      physiological and pathophysiological implications of these findings are
      discussed.

PMID- 11986396
TI  - Human balancing of an inverted pendulum: position control by small, ballistic
      like, throw and catch movements.
AB  - In standing, there are small sways of the body. Our interest is to use an
      artificial task to illuminate the mechanisms underlying the sways and to account
      for changes in their size. Using the ankle musculature, subjects balanced a large
      inverted pendulum. The equilibrium of the pendulum is unstable and quasi-regular
      sway was observed like that in quiet standing. By giving full attention to
      minimising sway subjects could systematically reduce pendulum movement. The
      pendulum position, the torque generated at each ankle and the soleus and tibialis
      anterior EMGs were recorded. Explanations about how the human inverted pendulum
      is balanced usually ignore the fact that balance is maintained over a range of
      angles and not just at one angle. Any resting equilibrium position of the
      pendulum is unstable and in practice temporary; movement to a different resting
      equilibrium position can only be accomplished by a biphasic 'throw and catch'
      pattern of torque and not by an elastic mechanism. Results showed that balance
      was achieved by the constant repetition of a neurally generated ballistic-like
      biphasic pattern of torque which can control both position and sway size. A
      decomposition technique revealed that there was a substantial contribution to
      changes in torque from intrinsic mechanical ankle stiffness; however, by itself
      this was insufficient to maintain balance or to control position. Minimisation of
      sway size was caused by improvement in the accuracy of the anticipatory torque
      impulses. We hypothesise that examination of centre of mass and centre of
      pressure data for quiet standing will duplicate these results.

PMID- 11986397
TI  - Molecular aspects of melanocytic dysplastic nevi.
AB  - Melanocytic dysplastic nevi were first described in both patients and their
      relatives who had one or several cutaneous malignant melanomas. Most of these
      dysplastic lesions are biologically stable, but some of them have severe
      histological atypia and can progress further to melanomas. Although several
      studies have suggested the etiological importance of dysplastic nevi in the
      development of melanomas, comprehensive reviews of the molecular changes in these
      dysplastic lesions are still scarce. To remedy this issue, this article analyzes
      the available molecular information about dysplastic nevi and provides the
      current state of knowledge regarding the karyotypic abnormalities of the
      melanoma/dysplastic nevus trait and the involvement of allelic loss, tumor
      suppressor genes, mismatch repair proteins, microsatellite instability,
      oncogenes, extracellular matrix proteins, and growth factors in the genesis of
      these lesions. These studies suggest that although some of these lesions
      represent "genetic dead-ends," others represent intermediate lesional steps in
      the melanoma tumorigenesis pathway.

PMID- 11986398
TI  - Immunoglobulin heavy chain gene analysis in lymphomas: a multi-center study
      demonstrating the heterogeneity of performance of polymerase chain reaction
      assays.
AB  - Determination of monoclonality through an evaluation of immunoglobulin heavy
      chain (IgH) gene rearrangements is a commonly performed and useful diagnostic
      assay. Many laboratories that perform this assay do so by the polymerase chain
      reaction (PCR). To evaluate current methods for performing IgH gene testing, 19
      different Association of Molecular Pathology (AMP) member laboratories analyzed
      29 blinded B cell and T cell lymphoid neoplasm samples of extracted DNA and
      formalin-fixed, paraffin-embedded (FFPE) tissue and were asked to complete a
      technical questionnaire. From this study, it is clear that Southern blot analysis
      remains the diagnostic gold standard, with a 100% diagnostic sensitivity and
      specificity. There was, however, remarkable heterogeneity in the performance of,
      and results obtained from, IgH PCR assays with diagnostic sensitivity ranging
      from over 90% to as low as 20%, when evaluating the same specimens. Many
      laboratories overestimate the diagnostic sensitivity of their IgH PCR assay, and
      there was a significant, and under appreciated, drop-off (from 61.3% to 41.8%) in
      detection in paired FFPE as compared with fresh/frozen tissues. Fixation has a
      dramatic impact on the inability to perform the test on FFPE (43.1%) versus DNA
      already extracted from fresh or frozen tissue (2.8%). A number of variables that
      affected the outcome of IgH PCR were identified. Strategies that improved the
      detection of monoclonal IgH rearrangements include: the addition of FRII to the
      FRIII upstream primer (increasing detection from 57.3% to 73.6%) and the use of
      the FR3A rather than the FR3 FRIII primer (increasing detection from 54.7% to
      69.7%). Although numerous variables (from DNA extraction to PCR product
      detection) were evaluated, making it difficult to mandate alterations in
      laboratory practice, these findings ought to prompt diagnostic molecular
      pathology laboratories to reevaluate their claims of sensitivity, as well as
      their methodologies. Both pathologists and surgeons need to ensure that not all
      submitted material is fixed, if there is adequate sample. Importantly, there is a
      need for greater standardization to reduce the unacceptably high false negative
      rate of this crucial diagnostic assay.

PMID- 11986399
TI  - Fluorescence PCR quantification of cyclin D1 expression.
AB  - We have used a continuous fluorescence monitoring method to assess cyclin D1 mRNA
      expression in a variety of hematological and non-hematological processes. We
      examined 14 cell lines, 11 reactive lymphoid tissues, and 57 primary
      hematopoietic neoplasms including mantle cell lymphoma (MCL) (n = 10), chronic
      lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 11), acute
      lymphoblastic leukemia/lymphoma (n = 15), follicular lymphoma (n = 6), peripheral
      T-cell lymphoma (PTCL) (n = 3), anaplastic large cell lymphoma (n = 3), hairy
      cell leukemia (n = 3), Burkitt lymphoma (n = 1), Burkitt-like lymphoma (n = 4),
      and plasmacytoma (n = 1) for the expression of cyclin D1 mRNA using fluorescently
      labeled sequence-specific hybridization probes. Fluorescence (F) was plotted
      against cycle (C) number over 45 cycles. The log-linear portion of the F versus C
      graph identified a fractional cycle number for threshold fluorescence. A beta
      globin mRNA transcript with equivalent amplification efficiency to that of cyclin
      D1 was used for assessment of RNA integrity and normalization. In general, the
      MCLs demonstrated substantially higher levels of cyclin D1 mRNA than the other
      lymphoproliferative processes. Moderately high levels of cyclin D1 mRNA were
      detected in one PTCL. On average, the CLL/SLL cases showed cyclin D1 mRNA levels
      two to three orders of magnitude lower than observed in the MCLs. Cell lines
      derived from non-hematopoietic neoplasms such as fibrosarcoma, small cell
      carcinoma, and neuroblastoma showed comparable or higher levels of cyclin D1 mRNA
      than the MCLs. Our results indicate that quantitative real-time reverse
      transcription (RT) polymerase chain reaction is a simple, rapid, and accurate
      technique for assessing cyclin D1 expression, and while it is not specific, it
      can reliably be used in the distinction of MCL from CLL/SLL.

PMID- 11986400
TI  - Measurements of human papillomavirus transcripts by real time quantitative
      reverse transcription-polymerase chain reaction in samples collected for cervical
      cancer screening.
AB  - Specific assays capable of distinguishing normal and atypical cervical changes
      from pre-cancerous lesions are direly needed to improve screening for cervical
      cancer. Specific genes transcripts that are up-regulated in dysplastic and cancer
      cells can be exploited as new markers for cervical cancer screening provided that
      they can be detected in heterogeneous populations such as those collected for
      Papanicolaou tests. We hypothesized that expression of the HPV early region gene
      E7 might distinguish between normal samples (absent expression) and high-grade
      lesions (detectable E7 expression). Our goal was to detect and measure gene
      expression in cells scraped from the cervix using real time quantitative reverse
      transcription-polymerase chain reaction (TaqMan). We have optimized collection
      and extraction procedures to provide suitable RNA for TaqMan analysis in clinical
      samples collected for cervical cancer screening and have demonstrated efficient
      measurements of housekeeping genes in these samples. HPV 16 or 18 early gene E7
      transcripts were detected in 47% of samples with a clinical diagnosis of high
      grade SIL and in 0% of cytologically normal samples (P = 0.006). Our study
      demonstrates that the TaqMan assay can be reliably applied to samples collected
      for cervical cancer screening, and that presence of detectable HPV E7 transcripts
      can distinguish between normal and abnormal samples.

PMID- 11986401
TI  - Competitive amplification and unspecific amplification in polymerase chain
      reaction with confronting two-pair primers.
AB  - Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an
      inexpensive, time-saving genotyping method that is applicable for most single
      nucleotide polymorphisms. To date, we have applied PCR-CTPP successfully for the
      genotyping of more than 30 polymorphisms. This paper demonstrates the differences
      in DNA amplification among different annealing temperatures of PCR-CTPP with
      given melting temperatures for four primers. The NQO1 C609T (Pro187Ser)
      polymorphism was used as an example. Two sets of four primers were applied for
      PCR-CTPP; the first set with different melting temperatures (Tms), and the second
      with similar Tms. The comparisons with one-pair primer PCR (allele-specific PCR)
      revealed that PCR-CTPP amplified DNA more specifically than allele-specific PCR.
      The primers with different Tms caused competitive DNA amplification for
      heterozygous genotype. Four primers with similar Tms amplified both alleles
      unspecifically at a lower annealing temperature, while the same DNA samples were
      correctly genotyped under an optimal annealing temperature. These findings are
      unique for PCR-CTPP, and important characteristics when the primers and annealing
      temperatures in PCR-CTPP are designed. The knowledge of these characteristics
      will extend the applicability of PCR-CTPP for polymorphism genotyping.

PMID- 11986402
TI  - Diagnosis of five spinocerebellar ataxia disorders by multiplex amplification and
      capillary electrophoresis.
AB  - The autosomal-dominant spinocerebellar ataxias (ADCA) are a heterogeneous group
      of neurodegenerative disorders with variable expression and phenotypic overlap.
      An accurate diagnosis relies on detection of a mutation in a specific causative
      gene, which is typically an abnormal number of CAG trinucleotide repeats. To
      streamline testing in a clinical setting, we converted our current panel of tests
      for the spinocerebellar ataxias (SCA) types SCA1, SCA2, SCA3, SCA6, and SCA7 from
      five independent amplification reactions analyzed by polyacrylamide gel
      electrophoresis (PAGE) to a single multiplex amplification reaction analyzed by
      capillary electrophoresis (CE). Multiplex amplification was facilitated by the
      use of chimeric primers; different lengths and fluorochromes distinguished the
      amplicons. During CE with commercially available molecular weight standards, the
      SCA amplicons migrated faster than predicted, thereby underestimating their
      length compared to that determined previously by PAGE. This was observed to
      varying degrees for each of the five loci, with the greatest size differential
      occurring in amplicons with greater (CAG)(n). To determine accurate amplicon
      length, and therefore an accurate number of CAG repeats, a size correction
      formula was calculated for each locus. This multiplex semi-automated assay has
      been reliable during 1 year of use in a clinical setting during which 57 samples
      were tested and five positive samples were detected.

PMID- 11986403
TI  - A 39-bp deletion polymorphism in PTEN in African American individuals:
      implications for molecular diagnostic testing.
AB  - Germline mutations in the PTEN/MMAC1/TEP1 tumor suppressor gene cause Cowden
      syndrome (CS), a hereditary hamartoma-tumor syndrome with an increased risk of
      breast, thyroid, and endometrial cancers, and seemingly unrelated developmental
      disorders, such as Bannayan-Riley-Ruvalcaba (BRR) syndrome, Proteus, and Proteus
      like syndromes. Data to date suggest that irrespective of the clinical
      presentation, the identification of a PTEN mutation should trigger medical
      management which includes cancer surveillance. Clinic-based molecular diagnostic
      testing for germline PTEN mutations has been available for at least 2 years. This
      study reports on the finding of a previously unobserved heterozygous alteration
      (IVS7-15-->53del39) found in an African American individual who had features of
      CS. Further investigation revealed that 12 of 42 (28.6%) African American
      controls, but not individuals of Caucasian or Japanese origin, also carried this
      heterozygous 39-bp deletion in PTEN. Due to its location immediately upstream of
      the splicing site of exon 8, this polymorphism could be mistaken for a
      deleterious mutation in the PTEN.

PMID- 11986404
TI  - T cell receptor gamma-chain gene polymerase chain reaction to diagnose central
      nervous system involvement by cutaneous T cell lymphoma.
AB  - The authors describe a patient who was suspected of having cutaneous T cell
      lymphoma involvement of the brain despite repeatedly negative cerebrospinal fluid
      (CSF) cytology, inconclusive flow cytometry, and no discrete lesion for brain
      biopsy. The diagnosis was made by polymerase chain reaction (PCR) analysis that
      showed a monoclonal T cell receptor gamma-chain gene rearrangement in the CSF,
      identically sized to that present in a skin biopsy specimen. Thus, PCR could be
      used early and routinely to diagnose central nervous system spread of T cell
      lymphomas, because of its potentially superior sensitivity and specificity to CSF
      cytology.

PMID- 11986406
TI  - Image in clinical medicine. Left ventricular thrombus.

PMID- 11986407
TI  - Beta-blockers for stable heart failure.

PMID- 11986408
TI  - Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha.
AB  - BACKGROUND: There are few effective treatments for ankylosing spondylitis, which
      causes substantial morbidity. Because of the central role of tumor necrosis
      factor alpha in the spondyloarthritides, we performed a randomized, double-blind,
      placebo-controlled trial of etanercept, a recombinant human tumor necrosis factor
      receptor (p75):Fc fusion protein, in patients with ankylosing spondylitis.
      METHODS: Forty patients with active, inflammatory ankylosing spondylitis were
      randomly assigned to receive twice-weekly subcutaneous injections of etanercept
      (25 mg) or placebo for four months. The primary end point was a composite of
      improvements in measures of morning stiffness, spinal pain, functioning, the
      patient's global assessment of disease activity, and joint swelling. Patients
      were allowed to continue taking nonsteroidal antiinflammatory drugs, oral
      corticosteriods (< or =10 mg per day), and disease-modifying antirheumatic drugs
      at stable doses during the trial. RESULTS: Treatment with etanercept resulted in
      significant and sustained improvement. At four months, 80 percent of the patients
      in the etanercept group had a treatment response, as compared with 30 percent of
      those in the placebo group (P=0.004). Improvements over base-line values for
      various measures of disease activity, including morning stiffness, spinal pain,
      functioning, quality of life, enthesitis, chest expansion, erythrocyte
      sedimentation rate, and C-reactive protein, were significantly greater in the
      etanercept group. Longitudinal analysis showed that the treatment response was
      rapid and did not diminish over time. Etanercept was well tolerated, with no
      significant differences in rates of adverse events between the two groups.
      CONCLUSIONS: Treatment with etanercept for four months resulted in rapid,
      significant, and sustained improvement in patients with ankylosing spondylitis.

PMID- 11986409
TI  - Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking
      agents.
AB  - BACKGROUND: Beta-blocker therapy may improve cardiac function in patients with
      idiopathic dilated cardiomyopathy. We tested the hypothesis that beta-blocker
      therapy produces favorable functional effects in dilated cardiomyopathy by
      altering the expression of myocardial genes that regulate contractility and
      pathologic hypertrophy. METHODS: We randomly assigned 53 patients with idiopathic
      dilated cardiomyopathy to treatment with a beta-adrenergic-receptor blocking
      agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA)
      for contractility-regulating genes (those encoding beta1- and beta2-adrenergic
      receptors, calcium ATPase in the sarcoplasmic reticulum, and alpha- and beta
      myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy
      (beta-myosin heavy chain and atrial natriuretic peptide) was measured with a
      quantitative reverse-transcription polymerase chain reaction in total RNA
      extracted from biopsy specimens of the right ventricular septal endomyocardium.
      Myocardial levels of beta-adrenergic receptors were also measured. Measurements
      were conducted at base line and after six months of treatment, and changes in
      gene expression were compared with changes in the left ventricular ejection
      fraction as measured by radionuclide ventriculography. RESULTS: Twenty-six of 32
      beta-blocker-treated patients (those with complete mRNA measurements) had an
      improvement in left ventricular ejection fraction of at least 5 ejection-fraction
      (EF) units (mean [+/-SE] increase, 18.8+/-1.8). As compared with the six beta
      blocker-treated patients who did not have a response (mean change, a decrease of
      2.5+/-1.8 EF units), those who did have a response had an increase in
      sarcoplasmic-reticulum calcium ATPase mRNA and alpha-myosin heavy chain mRNA and
      a decrease in beta-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum
      calcium ATPase was not present in the patients in the placebo group who had a
      spontaneous response. There were no differences between those who had a response
      and those who did not in terms of the change in mRNA or protein expression of
      beta-adrenergic receptors. CONCLUSIONS: In idiopathic dilated cardiomyopathy,
      functional improvement related to treatment with beta-blockers is associated with
      changes in myocardial gene expression.

PMID- 11986410
TI  - An outbreak of mycobacterial furunculosis associated with footbaths at a nail
      salon.
AB  - BACKGROUND: In September 2000, a physician in northern California described four
      patients with persistent, culture-negative boils on the lower extremities. The
      patients had received pedicures at the same nail salon. We identified and
      investigated an outbreak of Mycobacterium fortuitum furunculosis among customers
      of this nail salon. METHODS: Patients were defined as salon customers with
      persistent skin infections below the knee. A case-control study was conducted
      that included the first 48 patients identified, and 56 unaffected friends and
      family members who had had a pedicure at the same salon served as controls.
      Selected M. fortuitum isolates, cultured from patients and the salon environment,
      were compared by pulsed-field gel electrophoresis. RESULTS: We identified 110
      customers of the nail salon who had furunculosis. Cultures from 34 were positive
      for rapidly growing mycobacteria (32 M. fortuitum and 2 unidentified). Most of
      the affected patients had more than 1 boil (median, 2; range, 1 to 37). All
      patients and controls had had whirlpool footbaths. Shaving the legs with a razor
      before pedicure was a risk factor for infection (70 percent of patients vs. 31
      percent of controls; adjusted odds ratio, 4.8; 95 percent confidence interval,
      2.1 to 11.1). Cultures from all 10 footbaths at the salon yielded M. fortuitum.
      The M. fortuitum isolates from three footbaths and 14 patients were
      indistinguishable by electrophoresis. CONCLUSIONS: We identified a large outbreak
      of rapidly growing mycobacterial infections among persons who had had footbaths
      and pedicures at one nail salon. Physicians should suspect this cause in patients
      with persistent furunculosis after exposure to whirlpool footbaths.

PMID- 11986411
TI  - Image in clinical medicine. Bronchiectasis with Mycobacterium avium complex
      infection.

PMID- 11986412
TI  - Participation in research and access to experimental treatments by HIV-infected
      patients.
AB  - BACKGROUND: Although there is concern that minority groups and women are
      underrepresented in research involving patients with human immunodeficiency virus
      (HIV) infection, the available data are inconclusive. METHODS: We used nationally
      representative data from the HIV Cost and Services Utilization Study to determine
      the characteristics of the participants and nonparticipants in trials of
      medications for HIV infection and whether or not patients had access to
      experimental treatments. A probability sample of 2864 persons, representing all
      231,400 adults with known HIV infection who are cared for in the contiguous
      United States, were interviewed on three occasions between 1996 and 1998. They
      were asked about participation in clinical research studies of medications and
      past receipt of experimental medications for HIV. RESULTS: We estimate that 14
      percent of adults receiving care for HIV infection participated in a medication
      trial or study; 24 percent had received experimental medications; and 8 percent
      had tried and failed to obtain experimental treatments. According to multivariate
      models, non-Hispanic blacks and Hispanics were less likely to be participating in
      trials than non-Hispanic whites (odds ratio for participation among non-Hispanic
      blacks, 0.50 [95 percent confidence interval, 0.28 to 0.91]; odds ratio among
      Hispanics, 0.58 [95 percent confidence interval, 0.37 to 0.93]) and to have
      received experimental medications (odds ratios, 0.41 [95 percent confidence
      interval, 0.32 to 0.54] and 0.56 [95 percent confidence interval, 0.41 to 0.78],
      respectively). Patients who were cared for in private health maintenance
      organizations were less likely to participate in trials than those with fee-for
      service insurance (odds ratio, 0.43 [95 percent confidence interval, 0.21 to
      0.88]). Women were not underrepresented in research trials and had a similar
      likelihood of receiving experimental treatments. CONCLUSIONS: Among patients with
      HIV infection, participation in research trials and access to experimental
      treatment is influenced by race or ethnic group and type of health insurance.

PMID- 11986413
TI  - Bronchiectasis.

PMID- 11986414
TI  - Clinical problem-solving. One foot away.

PMID- 11986415
TI  - Anti-TNF-alpha therapy for ankylosing spondylitis--a specific or nonspecific
      treatment?

PMID- 11986416
TI  - Racial disparities in clinical trials.

PMID- 11986417
TI  - IRB reform.

PMID- 11986418
TI  - A central institutional review board for multi-institutional trials.

PMID- 11986419
TI  - Chimerism of the transplanted heart.

PMID- 11986420
TI  - Prevention of relapse in schizophrenia.

PMID- 11986421
TI  - Coronary magnetic resonance angiography.

PMID- 11986422
TI  - Irinotecan in small-cell lung cancer.

PMID- 11986423
TI  - Hereditary periodic fever.

PMID- 11986424
TI  - Head and neck cancer.

PMID- 11986425
TI  - Long-term follow-up of Hodgkin's disease trial.

PMID- 11986426
TI  - Improving protection for research subjects.

PMID- 11986427
TI  - Rising prevalence of antidepressants among US youths.
AB  - OBJECTIVE: To examine changes in antidepressant (ATD) prevalence and the
      sociodemographic and clinical correlates of ATD use among youths who are treated
      in community practice settings. METHODS: A retrospective study was undertaken
      using large data sets from 3 US sites. Outpatient prescription and clinical
      service records of youths who were aged 2 to 19 and enrolled in Midwestern
      Medicaid (MWM) and mid-Atlantic Medicaid (MAM) state programs and a group-model
      health maintenance organization (HMO) were organized into seven 1-year cross
      sectional data sets from 1988 through 1994 to evaluate ATD utilization patterns.
      RESULTS: In 1994, ATD prevalence per 1000 youths was 19.10 (MWM), 17.78 (MAM),
      and 12.85 (HMO), which represented a consistent increase in prevalence from 1988
      1994: 2.9-fold (MWM), 4.6-fold (MAM), and 3.6-fold (HMO). Despite the rapidly
      expanding use of selective serotonin reuptake inhibitors prescribed mainly for
      depression, more than half of ATD use in 1994 was still attributable to tricyclic
      antidepressants prescribed mainly for attention-deficit/hyperactivity disorder.
      ATD prevalence was generally predominant among 10- to 14-year-old boys and among
      15- to 19-year-old girls. In the Medicaid populations, 42% (MAM) and 72% (MWM) of
      ATD-treated youths had primary care services, whereas the bulk of the remainder
      had psychiatric services. Attention-deficit/hyperactivity disorder followed by
      depression led the physician-reported primary care diagnoses associated with ATD
      use, whereas that diagnostic rank order was reversed for youths who received
      psychiatric services. CONCLUSIONS: ATD treatments among youths substantially
      increased in the 1990s. This was generated primarily by primary care providers,
      and thus evaluations of the outcome of ATD treatment need to target primary care
      in addition to psychiatric providers. Longitudinal study designs are needed to
      evaluate the use of ATDs in youths in regard to the duration of treatment,
      combination medications, and the reasons for treatment.

PMID- 11986428
TI  - Factors associated with prescription drug expenditures among children: an
      analysis of the Medical Expenditure Panel survey.
AB  - OBJECTIVE: Pharmaceutical costs have reached 14% of total health care costs in
      the United States and continue to rise. Many studies have looked at factors that
      influence utilization of hospital and ambulatory care services in the pediatric
      population. This study examines the factors that influence utilization of
      prescription drugs in the pediatric population. METHODS: Data from the 1996
      Medical Expenditure Panel Survey (MEPS) were used in the analysis. A 2-part
      multivariate regression analysis was conducted using pediatric (ages 0-17)
      prescription drug expenditures as the dependent variable. Independent variables
      were constructed using demographic variables, socioeconomic variables, health
      status, and medical conditions. RESULTS: Black children are less likely than
      white children to use any prescription drug (odds ratio: 0.67). Similarly,
      uninsured children are less likely than privately insured children to use any
      prescription drug (odds ratio: 0.62). Among children who had any prescription
      drug expenditure in 1996, children who are black, Asian, and Hispanic had lower
      prescription drug expenditures than children who are white. Children who are
      uninsured had lower expenditures than children who are privately insured.
      Children in near-poor families had lower prescription drug expenditures than
      those in high-income families, even after controlling for insurance status.
      Children who are covered by Medicaid had comparable prescription drug
      expenditures to children who are covered by private insurance. CONCLUSION:
      Socioeconomic characteristics such as race, insurance status, and family income
      levels had significant impact on pediatric prescription drug expenditures, even
      after controlling for the influences of health status and medical conditions.

PMID- 11986429
TI  - Psychotropic medication use in a population of children who have attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: Recent reports suggest a trend of increasing prevalence of
      psychotropic drug prescriptions among children with attention
      deficit/hyperactivity disorder (ADHD); however, reasons for the increased use of
      such medications is unclear. The objectives of this study were to examine
      differences in nonstimulant psychotropic medication fills between children with
      and without identified ADHD and to assess associations with non-ADHD
      neurobehavioral disorders. METHODS: A population-based retrospective matched
      cohort study was conducted of a large group model health maintenance organization
      located in western Washington State. Eligible patients were children who were
      ages 3 to 17 years and were continuously enrolled and used services from January
      1 to December 31, 1997 (N = 57 216). Children with ADHD were identified by a
      diagnosis of ADHD or a pharmacy fill for a stimulant medication using automated
      patient files. Children without ADHD were randomly selected and matched 4:1 to
      children with ADHD on age and gender. Neurobehavioral disorders and pharmacy
      fills for psychotropic medications were measured. RESULTS: During 1997, 2992
      children were identified as having ADHD (5.2%). These children were more likely
      to have a diagnosis of a non-ADHD neurobehavioral disorders (adjusted odds ratio:
      6.3; 95% confidence interval: 5.4-7.3) than children without ADHD. Although most
      (78%) were treated with stimulant medications, children who were identified as
      having ADHD were also more likely to receive pharmacy fills for nonstimulant
      medications than were children without ADHD. Nonstimulant medications were more
      often used along with stimulant medications and were frequently prescribed in
      association with ADHD after controlling for other disorders. CONCLUSIONS:
      Children who were identified as having ADHD were more likely to have a diagnosis
      of other neurobehavioral disorders and to receive nonstimulant psychotropic
      medications than were children without ADHD. Because many of these drugs have
      little or no empirical basis in the treatment of ADHD, the rationale for their
      use is less clear. Future research to examine the use, effectiveness, and safety
      of these medications alone and in combination in children with ADHD is urgently
      needed.

PMID- 11986430
TI  - Parent and physician attitudes regarding electronic communication in pediatric
      practices.
AB  - OBJECTIVE: To determine 1) the electronic mail (e-mail) capabilities of families,
      general pediatricians (GPs), and subspecialty pediatricians (SPs) from an
      integrated pediatric health care delivery system and 2) the knowledge base and
      attitudes of these groups regarding the potential issues involved in using e-mail
      for physician-patient communication. METHODS: Parents were interviewed in the
      offices of participating practices using a standardized survey tool.
      Pediatricians and staff were interviewed using a separate instrument. The data
      were entered into a database for analysis. RESULTS: A total of 325 parents and 37
      physicians were interviewed. Fifty-seven percent of the 161 parents who were
      interviewed at the GP offices and 66% of the 164 families that were interviewed
      at SP offices had access to e-mail. Parents aged 31 to 40 years were
      significantly more likely to have access to e-mail than parents of other age
      groups. Access to e-mail increased with family income and parental education.
      Most (74%) parents who were interviewed expressed interest in using e-mail to
      contact their child's physician/physician's office for several purposes,
      including getting information or test results, scheduling appointments, and/or
      discussing a particular symptom. Although both groups of parents expressed
      concerns about confidentiality, parents at the GP offices were significantly more
      concerned (median(GP) = 95 vs median(SP) = 70). Seventy-four percent of GPs and
      100% of SPs had access to e-mail; however, 79% did not want to use e-mail for
      physician-patient communication, citing concerns about confidentiality and the
      time demands that patient e-mail might engender. CONCLUSIONS: The majority of
      parents and pediatricians at both general and subspecialty pediatric offices are
      capable of communicating electronically. Parents and pediatricians are aware of
      the issues surrounding e-mail use for patient communication. Most parents express
      an interest in using e-mail for patient-physician communications, whereas most
      physicians are opposed to this practice.

PMID- 11986431
TI  - Mortality in low birth weight infants according to level of neonatal care at
      hospital of birth.
AB  - OBJECTIVE: In 1976, the Committee on Perinatal Health recommended that hospitals
      with no neonatal intensive care unit (NICU) or intermediate NICUs transfer high
      risk mothers and infants that weigh <2000 g to a regional NICU. This standard was
      based on expert opinion and has not been validated carefully. This study
      evaluated the effect of NICU level and patient volume at the hospital of birth on
      neonatal mortality of infants with a birth weight (BW) of <2000 g. METHODS: Birth
      certificates of 16 732 singleton infants who had a BW of <2000 g and were born in
      nonfederal hospitals in California in 1992 and 1993 were linked to death
      certificates and to discharge abstracts. The hospitals were classified by the
      level of NICU: no NICU, no intensive care; intermediate NICU, intermediate
      intensive care; community NICU, expanded intermediate intensive care; and
      regional NICU, tertiary intensive care. A logistic regression model that
      controlled for demographic risks, diagnoses, transfer, average NICU census, and
      NICU level was estimated using death within the first 28 days or first year of
      life if continuously hospitalized as the main outcome measure. RESULTS: Compared
      with birth in a hospital with a regional NICU, risk-adjusted mortality of infants
      with BW of <2000 g was higher when birth occurred in hospitals with no NICU (odds
      ratio [OR]: 2.38; 95% confidence interval [CI]: 1.81-3.13), an intermediate NICU
      (OR: 1.92; 95% CI: 1.44-2.54), or a small (average census <15) community NICU
      (OR: 1.42; 95% CI: 1.14-1.76). Risk-adjusted mortality for infants who were born
      in hospitals with a large (average census > or =15) community NICU was not
      statistically different compared with those with a regional NICU (OR: 1.11; 95%
      CI: 0.87-1.43). Except for large community NICUs, all of these ORs are larger
      when the data are restricted to infants with BW of <1500 g or BW of <1250 g and
      smaller for BW between 1250 g and 1999 g and 1500 g and 1999 g. For large
      community NICUs, the results are similar for the smaller BW intervals and
      significant only for the larger BW interval. CONCLUSIONS: These results support
      the recommendation that hospitals with no NICU or intermediate NICUs transfer
      high-risk mothers with estimated fetal weight of <2000 g to a regional NICU. For
      infants with BW of <2000 g, birth at a hospital with a regional NICU is
      associated with a lower risk-adjusted mortality than birth at a hospital with no
      NICU, intermediate NICU of any size, or small community NICU. Subsequent neonatal
      transfer to a regional NICU only marginally decreases the disadvantage of birth
      at these hospitals. The evidence for the few hospitals with large community NICUs
      is mixed. Although the data point to higher mortality in large community NICUs,
      they are not conclusive and additional study is needed on the mortality effects
      of large community NICUs. Greater efforts should be made to deliver infants with
      expected BW of <2000 g at hospitals with regional NICUs.

PMID- 11986432
TI  - Performance profiles: the influence of patient satisfaction data on physicians'
      practice.
AB  - OBJECTIVE: Health maintenance organizations and other payers increasingly use
      patient satisfaction data to profile physician performance. Little is known about
      physicians' use of patient satisfaction information or how profiles affect
      individual physician behaviors. The objective of this study was to examine
      primary care physicians' perceptions of performance profiles based on patient
      satisfaction data, whether physicians use profiles to change practice behaviors,
      and which profile components physicians think are important for assessing quality
      of care. METHODS: A written survey was conducted in 1998 in Massachusetts with
      810 primary care physicians (304 pediatricians, 201 family practitioners, 305
      internists) who had at least 100 patients in a large managed care plan and had
      received 1 or more profiles based on patient satisfaction data. Physicians in
      training were excluded. Physicians' perceptions of profiles and their reported
      use to change practice behaviors were measured. RESULTS: The response rate was
      68%. Twenty-three percent reported that profiles were very or extremely useful
      for improving care. Only 7% reported using profiles often or always to change
      care. Although specific profile components related to interpersonal aspects of
      care were rated more useful, <11% reported using profiles often or always to make
      changes on any individual component. A majority, 67% to 89%, reported making no
      or minor changes on profile components. Responses did not vary by specialty,
      demographics, or practice characteristics. Physicians rated interpersonal factors
      (eg, ability to communicate with patients, ability to show caring and empathy) as
      the most important indicators of quality of care; they report having the most
      control over these factors. Office factors (eg, staying on schedule, ease of
      scheduling appointments) were ranked as least important for assessing quality of
      care. CONCLUSION: Although health maintenance organizations and other payers
      increasingly use patient satisfaction reports to profile individual physicians
      and guide physician compensation and health plan participation, <25% of primary
      care physicians find profiles useful for improving patient care and even fewer
      report using profiles to change practice. Profiles likely have limited influence
      on behavior changes. Payers who invest in profiles may find it advantageous to
      focus on health plans and practice facilities rather than on individual
      physicians.

PMID- 11986433
TI  - Ventilator-associated pneumonia in pediatric intensive care unit patients: risk
      factors and outcomes.
AB  - OBJECTIVES: To determine the rates, risk factors, and outcomes of ventilator
      associated pneumonia in pediatric intensive care unit (PICU) patients. METHODS: A
      prospective cohort study was conducted at the St Louis Children's Hospital PICU
      on all patients who were admitted to the PICU from September 1, 1999, to May 31,
      2000, except those who died within 24 hours, were > or =18 years of age, or were
      neonatal intensive care unit patients on extracorporeal membrane oxygenation. The
      primary outcome measured was the development of ventilator-associated pneumonia.
      Secondary outcomes were death and hospital and PICU length of stay. Multiple
      logistic regression analysis was performed to determine independent predictors
      for ventilator-associated pneumonia. RESULTS: There were 34 episodes of
      ventilator-associated pneumonia in 30 patients of 911 admissions (3.3%) and 595
      (5.1%) mechanically ventilated patients. The mean ventilator-associated pneumonia
      rate was 11.6/1000 ventilator days. By logistic regression analysis, genetic
      syndrome (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.01-5.46),
      reintubation (OR: 2.71; 95% CI: 1.18-6.21), and transport out of the PICU (OR:
      8.90; 95% CI: 3.82-20.74) independently predicted ventilator-associated
      pneumonia. CONCLUSIONS: Ventilator-associated pneumonia occurs at significant
      rates among mechanically ventilated PICU patients and is associated with
      processes of care. Additional studies are necessary to develop interventions to
      prevent ventilator-associated pneumonia.

PMID- 11986434
TI  - Evaluation of young children in contact with adult multidrug-resistant pulmonary
      tuberculosis: a 30-month follow-up.
AB  - SETTING: The Western Cape Province of South Africa, an area with a high
      tuberculosis (TB) incidence, where initial multidrug resistance (MDR) among adult
      TB cases was 1.1% during 1992-1993. OBJECTIVE: To determine the long-term
      prevalence of TB infection and disease in children in household contact with
      adults with MDR pulmonary TB, and to establish the efficacy of chemoprophylaxis
      in preventing disease in these children. METHOD: Children <5 years old in contact
      with 73 MDR TB adults were evaluated. Disease was treated by prescribing at least
      2 drugs to which the adult's strain was susceptible. The remaining children were
      classified as infected or noninfected and received chemoprophylaxis according to
      the index's strain susceptibility or were followed up and treated when indicated.
      All were followed up for 30 months. RESULTS: At the initial evaluation 125
      children were seen, median age 27.5 months. Of these, 119 were followed up.
      Fourteen (12%) had disease, 61 (51%) were infected only, and 44 (37%) were
      noninfected. By 30-month follow-up, 29 (24%) had developed disease and 64 (54%)
      were infected only. Four adult-child pair Mycobacterium tuberculosis isolates
      were compared by DNA fingerprinting; 3 were identical. All children who developed
      TB disease were clinically cured. Two (5%) of 41 children who received
      appropriate chemoprophylaxis and 13 (20%) of 64 who did not, developed TB during
      follow-up (odds ratio: 4.97). CONCLUSION: The study confirms MDR TB transmission
      to childhood contacts. Seventy-eight percent of children were infected or
      developed disease. Appropriate chemoprophylaxis may prevent disease in these
      children.

PMID- 11986435
TI  - Comparison between simultaneously recorded amplitude integrated
      electroencephalogram (cerebral function monitor) and standard
      electroencephalogram in neonates.
AB  - OBJECTIVE: To assess the value and the limitations of amplitude integrated
      electroencephalogram (EEG) using the cerebral function monitor (CFM) in
      comparison with standard EEG in neonates who have hypoxic ischemic encephalopathy
      or were suspected of having convulsions. METHODS: In 36 neonates with a
      gestational age > or =36 weeks, CFM and simultaneously recorded EEG traces were
      analyzed off-line and independently classified. CFM background activity:
      continuous normal voltage; continuous normal voltage, slightly discontinuous
      (DNV); burst-suppression (BS); continuous extremely low voltage; flat tracing.
      CFM epileptiform activity: suspected epileptic activity, single seizure (SS),
      repetitive seizures (RS), status epilepticus (SE). EEG background activity:
      normal, depressed, low voltage undifferentiated, excessive discontinuity, BS, no
      activity. Epileptiform activity: interictal unifocal, interictal multifocal,
      ictal unifocal, ictal multifocal, SE. RESULTS: A total of 33 traces were suitable
      for analysis. Interobserver agreement on background activity was reached in 31
      cases (kappa = 0.92) for CFM and in 27 cases (kappa = 0.74) for EEG. There was
      full agreement on CFM ictal activity (RS, SS, or SE) and EEG ictal activity. A
      normal CFM (continuous normal voltage) corresponded with a normal or a depressed
      EEG in 90% of the cases. The positive predictive value for a severely abnormal
      CFM (BS, continuous extremely low voltage, flat tracing) to correspond with a
      severely abnormal EEG (excessive discontinuity, BS, low voltage undifferentiated,
      no activity) was 100% (negative predictive value, 80%; sensitivity, 76%;
      specificity, 100%). DNV (10) on CFM corresponded either with depressed (6) or
      excessive discontinuity (4) on EEG. Ictal activity on EEG corresponded with SS,
      RS, or SE on CFM in 8 cases (sensitivity, 80%; specificity, 100%; positive
      predictive value, 100%; negative predictive value, 92%). CONCLUSION: CFM is a
      reliable tool for monitoring both background patterns (especially normal and
      severely abnormal) and ictal activity. Certain focal, low amplitude, and very
      short periods of seizure discharges can be missed. We recommend using CFM as a
      monitoring device and performing intermittent standard EEG whenever there is any
      doubt about the classification of the CFM (ie, DNV pattern or suspected
      epileptiform activity).

PMID- 11986436
TI  - Efficacy of the ketogenic diet for infantile spasms.
AB  - OBJECTIVE: The objective of this study was to determine whether the ketogenic
      diet is safe, well-tolerated, and efficacious in the treatment of infantile
      spasms. METHODS: During a 4-year period, 23 children with infantile spasms, aged
      5 months to 2 years, were started on the ketogenic diet; 9 (39%) had symptomatic
      infantile spasms, and 16 (70%) had hypsarrhythmia. Children had an average
      prediet exposure to 3.3 anticonvulsants. Two children were enrolled before any
      medication had been tried. Seizure reduction was analyzed retrospectively, using
      parent reports and electroencephalograms (EEGs) when available. RESULTS: At 3, 6,
      9, and 12 months, 38%, 39%, 53%, and 46%, respectively, of all patients currently
      on the diet were >90% improved (3 were seizure-free at 12 months); 67%, 72%, 93%,
      and 100% were >50% improved. Fifty-six percent remained on the diet at 12 months,
      46% of whom were >90% improved and 100% were >50%. Fifty percent of those with
      hypsarrhythmia and follow-up EEGs had EEG improvement. Fifty-seven percent had
      their medications reduced or discontinued by 12 months. Fifty-seven percent had
      improvement in development, which was correlated with seizure control.
      Independent factors that predicted improvement included age younger than 1 year
      and previous exposure to 3 or fewer anticonvulsants. No child has died, and 7
      children had diet-related adverse reactions (nephrolithiasis, gastroesophageal
      reflux). DISCUSSION: The ketogenic diet is a safe, well-tolerated, and possibly
      effective potential alternative to other therapies for infantile spasms.

PMID- 11986437
TI  - Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants.
AB  - OBJECTIVE: In adults, a single dose of 250 mg of caffeine may decrease cerebral
      blood flow by 30%. In preterm infants, caffeine is commonly used for the
      treatment and prophylaxis of apnea. The purpose of this investigation was to
      assess effects of caffeine on circulatory parameters in preterm infants. METHODS:
      We studied 16 preterm neonates with a mean gestational age (mean +/- standard
      deviation) of 31 +/- 1.2 weeks (range: 29-33 weeks), birth weight of 1400 +/- 380
      g (range: 625-2060 g), and postnatal age of 24 to 72 hours before and 1 and 2
      hours after an oral loading dose of 25 mg/kg pure caffeine. We investigated left
      ventricular output (LVO), cerebral blood flow velocity (BFV) of the internal
      carotid artery (ICA) and the anterior cerebral artery, and intestinal BFV of the
      celiac artery and superior mesenteric artery by Doppler sonography. RESULTS: Mean
      BFV in the ICA decreased significantly 1 (17%) and 2 hours (22%) after caffeine
      administration. Mean BFV in the anterior cerebral artery showed a reduction of
      14% after 2 hours. The mean BFV in the superior mesenteric artery decreased
      significantly 1 and 2 hours after caffeine administration (30%). Mean BFV in the
      celiac artery showed a significant reduction of 14% 1 hour after caffeine. No
      changes were observed in LVO, blood pressure, and heart rate. CONCLUSION: Oral
      administration of a high loading dose of caffeine results in marked reduction of
      cerebral and intestinal BFV, without changing LVO, blood pressure, and heart
      rate.

PMID- 11986438
TI  - Demography of pediatric primary care in Europe: delivery of care and training.
AB  - OBJECTIVE: The Union of National European Pediatric Societies and Associations
      recognized the lack of information regarding demography of delivery of care and
      training for the doctors who care for children in Europe. Therefore, the Union of
      National European Pediatric Societies and Associations studied factors and
      explanations for the variation between countries regarding pediatric primary care
      (PPC) and community pediatrics (CP) as well as the extent of formal training
      provided for those who take care of children at the community level. METHODS: An
      explanatory letter and a questionnaire with 12 questions regarding delivery of
      PPC and CP and training was mailed to the president of each of 41 national
      pediatric societies in Europe. Statistical data about population, country's
      income, and infant mortality rate (IMR) were also obtained from World Health
      Organization data. Statistical analysis using multivariate and linear regression
      was conducted to ascertain which variables were associated with IMR. Descriptive
      statistics regarding demography and training are also reported. RESULTS: In 1999,
      a total of 167 444 pediatricians served a population of 158 million children who
      were younger than 15 years and living in the 34 reporting European countries. The
      median number of children per pediatrician was 2094; this varied from 401 to 15
      150. A pediatric system for PPC existed in 12 countries; 6 countries had a
      general practitioner system, and a combined system was reported from 16
      countries. Pediatricians did not work at the primary care level at all in 3
      countries. In 14 of 34 countries, pediatricians worked in various aspects of
      community medicine, such as developmental pediatrics, well-infant care, school
      physicians, and so forth. IMR was lower in countries with a higher income per
      capita. In addition, a pediatric system of primary care had a protective effect
      when looking at IMR as the outcome. In 75% of the countries, some form of
      training in pediatric care for pediatricians was reported; the corresponding data
      for general practitioners was 60%. Community-based teaching programs were offered
      to pediatricians and general practitioners in a minority of countries only.
      CONCLUSIONS: At the end of the century, Europe showed a considerable variation in
      both delivery of PPC and training for doctors who care for children. This study
      identified 3 different health care delivery systems for PPC, as well as 2 types
      of pediatricians who work in community-based settings. Formal training in PPC or
      CP for both pediatricians and general practitioners varied from established
      curricula to no teaching at all. Economic and sociopolitical issues, professional
      power, and geographical and historical factors may explain the differences in
      pediatric care among European countries.

PMID- 11986439
TI  - Association between infantile colic and carbohydrate malabsorption from fruit
      juices in infancy.
AB  - OBJECTIVE: To determine whether infantile colic (IC) is associated with
      malabsorption of carbohydrates present in fruit juices. METHODS: In this double
      blind study, parents of 30 healthy infants (5.1 +/- 0.7 months, 7.4 +/- 1.0 kg,
      64 +/- 4 cm) were administered a questionnaire to quantitatively assess IC.
      Thereafter, they were divided into 2 groups, 16 infants with and 14 without IC.
      Within each treatment group infants were fed 120 mL (16.3 +/- 2.0 mL/kg) of
      either white grape (sorbitol-free; 1:1 fructose-to-glucose ratio) or apple
      (sorbitol 0.5 g/dL; 2.6:1 fructose-to-glucose ratio) juice. Physical activity
      (PA), energy expenditure (EE), crying, and sleeping times were measured for 0.5
      and 3.0 hours before and after juice feeding, respectively, using the Enhanced
      Metabolic Testing Activity Chamber. Carbohydrate malabsorption was determined by
      breath hydrogen (BH(2)) gas analysis after juice feedings. Statistical
      differences between groups were determined by 2-way analysis of variance with the
      Tukey procedure. RESULTS: Infants with IC fed apple juice exhibited carbohydrate
      malabsorption as shown by increased BH(2) excretion, whereas those without IC
      absorbed carbohydrates normally when fed this juice. Infants fed apple juice with
      carbohydrate malabsorption cried more and consequently slept less during the last
      1.5 hours of the study. This was associated with increased PA and EE as compared
      with infants without IC fed apple juice. In contrast, infants fed white grape
      juice, regardless of IC, showed no increase in BH(2) excretion, PA, and EE.
      Furthermore, crying and sleeping times were unchanged in infants fed white grape
      juice regardless of the presence or absence of IC. CONCLUSIONS: IC was associated
      with carbohydrate malabsorption from fruit juices containing sorbitol and a high
      fructose-to-glucose ratio.

PMID- 11986440
TI  - Assent observed: children's involvement in leukemia treatment and research
      discussions.
AB  - OBJECTIVE: Assent is a critical issue in pediatric ethics that has not been well
      studied. We examined the role of older children in discussing a recent diagnosis
      of acute leukemia and treatment options, including participation in a randomized,
      clinical trial (RCT). DESIGN: Our sample was drawn from data collected as part of
      a larger, National Cancer Institute-funded study in which we observed, tape
      recorded, and transcribed the informed consent conference (ICC) for children with
      leukemia at 6 institutions. We analyzed the data for the child's presence and
      role, examined 5 discussion categories relevant to assent in the context of
      pediatric cancer treatment/research, conducted parent interviews, and
      administered clinician questionnaires to examine these issues. We report a
      qualitative analysis of 14 cases in which the child was present for the ICC.
      RESULTS: Clinicians varied with regard to whom they directed specific discussions
      when patients were present. Questions asked by the children predominantly related
      to details of the disease and treatment, with few questions about the RCT.
      Clinicians and parents attribute responsibility for decision-making about
      participation in RCTs in a variety of ways. In conferences that included the
      child-patient, parents asked significantly fewer questions than in other ICCs.
      CONCLUSION: There is significant variation among ICCs that include the older
      child. Additional empirical study of assent is warranted, and our data suggest
      several hypotheses that should be tested in future research.

PMID- 11986441
TI  - Validity of maternal report of prenatal alcohol, cocaine, and smoking in relation
      to neurobehavioral outcome.
AB  - OBJECTIVE: Evidence that mothers report higher levels of drinking retrospectively
      than during pregnancy has led some investigators to suggest that women
      systematically underreport alcohol antenatally and that alcohol-related deficits
      may actually reflect heavier prenatal exposure. This study is the first to
      compare the validity of antenatal and retrospective reports of pregnancy
      drinking, drug use, and smoking in relation to effects on infant neurobehavioral
      outcomes. METHODOLOGY: Three hundred fifty-four inner-city mothers were
      interviewed regarding their alcohol, drug use, and smoking during pregnancy and
      retrospectively at 13 months' postpartum. Their infants were assessed at 6.5, 12,
      and 13 months on a large battery of neurobehavioral assessments. RESULTS:
      Although higher levels of alcohol were reported retrospectively, the correlations
      of prenatal alcohol exposure with infant outcome were as strong or stronger for
      the antenatal measures and only the antenatal reports predicted poorer cognitive
      performance on the Bayley Scales and symbolic play, slower processing speed on
      the Fagan Test of Infant Intelligence and cross-modal transfer, and slower infant
      reaction time. Women also reported higher levels of cocaine and marijuana but not
      cigarette smoking retrospectively. Relations between cocaine use and smoking on
      birth size and gestational age were as strong for either report. No effects were
      detected in relation to either report of marijuana use during pregnancy.
      CONCLUSIONS: These findings suggest that antenatal alcohol interviews provide the
      most valid information and demonstrate the importance of assessing prenatal
      alcohol use during pregnancy to minimize the risk of failing to detect
      neurobehavioral deficits. Adverse effects were consistently seen at levels as low
      as 0.5 oz absolute alcohol/day (the equivalent of 7 drinks per week) based on
      maternal antenatal report. These data suggest that alcohol-related deficits do
      not reflect heavier prenatal exposure than that reported during pregnancy and
      that threshold values derived from antenatal reports are reasonably accurate.

PMID- 11986442
TI  - Viral respiratory infection in schoolchildren: effects on middle ear pressure.
AB  - OBJECTIVE: To evaluate the effect of uncomplicated viral respiratory infections
      (colds) on middle ear pressure in healthy school-aged children. METHODS: Children
      (ages 2-12) with normal tympanograms before onset of illness had bilateral
      tympanometry daily except weekends for 2 weeks after the onset of a cold.
      Nasopharyngeal secretion obtained at onset of illness was cultured for bacterial
      pathogens of otitis media using selective agars and tested for rhinovirus,
      coronavirus, respiratory syncytial virus, influenza A and B, and parainfluenza 1
      3 by reverse transcriptase polymerase chain reaction technology. Tympanometry was
      designated as abnormal with peak pressure of < or =-100 daPa or > or =50 daPa
      and/or a compliance peak of < 0.2 cm(3). RESULTS: Eighty-six colds were studied,
      82 in schoolchildren (5-12 years old) and 4 in 2- to 3-year-olds. Abnormal
      negative middle ear pressure occurred at least once during the 2 weeks after
      onset in 57 (66%) of the 86 colds. Tympanometry was abnormal in the first week
      after onset in 50 (88%) of the 57 colds and was abnormal on a single day in 17
      (30%) of the 57. The middle ear pressure abnormalities were intermittent and
      shifted from one ear to the other ear from day to day. Reverse transcriptase
      polymerase chain reaction was positive for a respiratory virus in 56 (65%) of the
      86 illnesses. Rhinovirus was found in 48% and respiratory syncytial virus in 14%.
      Pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae, or
      Moraxella catarrhalis) were detected in nasopharyngeal secretion in 29 (34%) of
      the 86 colds; the bacteria were in high titer (> or =10(3) cfu/mL) in 26 of the
      29 positive specimens. None developed illness that required a visit to a
      physician. Age, detection of a respiratory virus, and presence of bacterial
      pathogen in the nasopharyngeal secretion had a negligible effect on the
      occurrence of abnormal tympanometry. Occurrence of negative middle ear pressure
      in winter-spring colds was significantly greater than in fall colds for
      unexplained reasons. CONCLUSIONS: Transient negative middle ear pressure occurred
      in two thirds of uncomplicated colds in healthy children. This negative pressure,
      which may facilitate secondary viral or bacterial otitis media, seems to result
      from viral infection of the nasopharynx and distal tube causing bilateral
      eustachian tube dysfunction. Tympanometry provides an objective measure of the
      potential beneficial effects of investigational treatments on the risk of
      eustachian tube dysfunction/otitis media.

PMID- 11986443
TI  - Occurrence of celiac disease after onset of type 1 diabetes: a 6-year prospective
      longitudinal study.
AB  - OBJECTIVE: To investigate the prevalence of celiac disease in a large cohort of
      children and adolescents at the onset of type 1 diabetes and the occurrence of
      new cases during a 6-year follow-up. METHODS: We prospectively studied, by
      repeated serologic screening, 274 consecutive patients at the onset of type 1
      diabetes (age [mean +/- standard deviation]: 8.28 +/- 4.65 years) for 6
      subsequent years. One patient had a diagnosis of celiac disease before the onset
      of diabetes. The immunoglobulin A-antiendomysium antibody test was selected as
      the screening test; patients with positive results (++ or +++) or with 2
      consecutive weak positive tests (+) were considered appropriate for the jejunal
      biopsy. RESULTS: At diabetes onset, 15 (5.5%) of 273 patients tested positive
      with the antiendomysium test; jejunal biopsy was performed in 10, and celiac
      disease was diagnosed in 9. The prevalence of biopsy-confirmed celiac disease at
      the manifestation of diabetes was 3.6% (10 of 274 patients). Twelve more patients
      with a negative antiendomysium antibody test at diabetes onset tested positive
      during the follow-up within 4 years; 10 of them had biopsies performed, and 7 had
      celiac disease. Therefore, the overall prevalence of biopsy-confirmed celiac
      disease in the entire cohort of patients was 6.2%. The age at diabetes onset in
      patients with and without celiac disease was not different (7.88 +/- 5.69 vs 8.3
      +/- 4.58 years). The majority of cases of celiac disease were asymptomatic in
      their presentation, and no signs of overt malnutrition were documented.
      CONCLUSIONS: The prevalence of celiac disease in patients with type 1 diabetes is
      approximately 20 times higher than in the general population. Sixty percent of
      cases are already present at diabetes onset, mostly undetected, but an additional
      40% of patients develop celiac disease a few years after diabetes onset.
      Extending screening programs for celiac disease after the onset of type 1
      diabetes is recommended, even in the absence of clinical symptoms.

PMID- 11986444
TI  - Hepatitis A virus infections in the United States: model-based estimates and
      implications for childhood immunization.
AB  - OBJECTIVE: The high prevalence of antibody to hepatitis A virus (HAV) in the US
      population suggests that the incidence of infection is much higher than reported,
      but the infection rate is difficult to measure directly because of anicteric
      infection and underreporting. We present a model that reconciles the reported
      incidence of hepatitis A with the observed prevalence of antibody to HAV and
      provides an estimate of the true incidence of HAV infection. METHODS: In the
      model, reported incidence of hepatitis A in the United States was adjusted to
      account first for anicteric infection and then for underreporting and declining
      incidence over time such that the prevalence predicted by the model approximated
      that observed in 2 nationwide surveys. RESULTS: The model showed incidence in the
      susceptible population declining by 4.5% per year. As incidence declined early in
      the 1900s, the average age at infection increased, leading to a paradoxical
      increase in the incidence of icteric infection followed by a slow decline. The
      model estimated approximately 270 000 (range: 190 000-360 000) infections
      annually from 1980 to 1999, 10.4 times the number of hepatitis A cases actually
      reported during this period. More than half of these infections occurred in
      children who were younger than 10 years, most of which would have been clinically
      unrecognizable as hepatitis. CONCLUSIONS: These results suggest a large reservoir
      of infection in children and that interruption of transmission in children may
      substantially reduce incidence of hepatitis A overall.

PMID- 11986445
TI  - Jaundice as an early diagnostic sign of urinary tract infection in infancy.
AB  - OBJECTIVE: Urinary tract infections (UTIs) are a common clinical problem in
      febrile infants younger than 8 weeks old, with a prevalence between 5% and 11%.
      Previous studies have noted that jaundice may be one of the first signs of a
      bacterial infection in infants. Our goal was to determine the incidence of UTIs
      in asymptomatic, jaundiced infants younger than 8 weeks old and to determine
      which historical and laboratory parameters are associated with UTIs. METHODS: We
      prospectively evaluated asymptomatic, jaundiced infants younger than 8 weeks old
      for evidence of a UTI (defined as >10 000 colony-forming units per milliliter of
      a single pathogen, obtained by bladder catheterization). A serum fractionated
      bilirubin level was obtained on all study patients. Detailed questionnaires were
      completed, which included demographic information, prenatal, intrapartum, and
      postnatal events. RESULTS: Twelve (7.5%) of 160 infants had a UTI (95% confidence
      interval: 3.9%-12.7%). Isolated organisms included Escherichia coli, Enterobacter
      cloacae, Enterococcus, Klebsiella pneumoniae, group B Streptococcus,
      Streptococcus viridans, and Staphylococcus aureus. Patients with the onset of
      jaundice after 8 days of age had a higher incidence of UTI, 6 (50%) of 12 infants
      in the positive culture group, versus 15 (10%) of 148 infants in the negative
      culture group. Abnormal urinalysis and microscopy results were noted in 5 (42%)
      of 12 infants with a UTI, and 6 (55%) of 11 infants had abnormal renal ultrasound
      results. CONCLUSION: A UTI was found in 7.5% of asymptomatic, afebrile, jaundiced
      infants younger than 8 weeks old. In addition, infants with the onset of jaundice
      after 8 days of age or patients with an elevated conjugated bilirubin fraction
      were more likely to have a UTI. Therefore, we recommend that testing for a UTI be
      included as part of the evaluation in asymptomatic, jaundiced infants presenting
      to the emergency department.

PMID- 11986446
TI  - Efficacy and safety of tolazoline for treatment of severe hypoxemia in extremely
      preterm infants.
AB  - OBJECTIVE: To determine the efficacy of tolazoline as a rescue treatment for
      hypoxemia in preterm infants with respiratory distress syndrome. METHODS:
      Retrospective chart review on case series of infants weighing < 750 g at birth
      who received tolazoline during a severe hypoxemic episode while receiving maximal
      ventilator support for respiratory distress syndrome. A slow bolus infusion of
      low dose tolazoline (0.5 mg-2 mg/kg) mixed with plasmanate or normal saline (10
      mL/kg) was administered. Outcome measures evaluated included an increase in
      PaO(2) > or =20 mm Hg from pretreatment value and an increase in oxygen
      saturation to > or =90%. RESULTS: Forty-three infants with a mean gestational age
      and birth weight of 24 weeks and 581 g, respectively, received tolazoline. All
      infants were mechanically ventilated and required a fraction of inspired oxygen
      of 1.0. Oxygenation improved in 72% (31/43) of infants with a tolazoline dose of
      0.5 to 1.0 mg/kg. Of those who responded, PaO(2) values (mean +/- standard
      deviation) pretolazoline and posttolazoline were 32 +/- 7.5 mm Hg and 156 +/-
      114.9 mm Hg, respectively. In all responders, oxygen saturation increased to > or
      =90% within 30 minutes of tolazoline administration. Improvement in pH, pCO(2),
      oxygenation index, and mean airway pressure was also noted. Among nonresponders,
      pH decreased and pCO(2) increased after tolazoline. Minimal change in blood
      pressure was noted in both responders and nonresponders. Heart rate decreased by
      19 beats per minute among nonresponders compared with an increase of 3 beats per
      minute in those who responded to tolazoline. CONCLUSION: Tolazoline is an
      effective treatment of severe resistant hypoxemia in preterm infants who are
      already on vigorous ventilatory support.

PMID- 11986447
TI  - Racial/ethnic variation in asthma status and management practices among children
      in managed medicaid.
AB  - OBJECTIVE: Racial/ethnic disparities in hospitalization rates among children with
      asthma have been documented but are not well-understood. Medicaid programs, which
      serve many minority children, have markedly increased their use of managed care
      in recent years. It is unknown whether racial/ethnic disparities in health care
      use or other processes of care exist in managed Medicaid populations. This study
      of Medicaid-insured children with asthma in 5 managed care organizations aimed to
      1) compare parent-reported health status and asthma care processes among black,
      Latino, and white children and 2) test the hypothesis that racial/ethnic
      variations in processes of asthma care exist after adjusting for socioeconomic
      status and asthma status. METHODS: This cross-sectional study collected data via
      telephone interviews with parents and computerized records for Medicaid-insured
      children with asthma in 5 managed care organizations in California, Washington,
      and Massachusetts. The American Academy of Pediatrics (AAP) Children's Health
      Survey for Asthma was used to measure parent-reported asthma status. We used
      multivariate models to evaluate associations between race/ethnicity and asthma
      status while controlling for other sociodemographic variables. We evaluated
      racial/ethnic variations in selected processes of asthma care while controlling
      for other demographic variables and asthma status. RESULTS: The response rate was
      63%. Of the 1658 children in the respondent group, 38% were black, 19% were
      Latino, and 31% were white. Black children had worse asthma status than white
      children on the basis of the AAP asthma physical and emotional health scores,
      symptom-days, and school days missed in the past 2 weeks. Latino children had
      equivalent AAP scores but missed more school days than white children. On the
      basis of the AAP asthma physical health score, the black-white disparity
      persisted after adjusting for other sociodemographic variables. After adjusting
      for sociodemographic variables and asthma status, black and Latino children were
      less likely to be using inhaled antiinflammatory medication than white children
      (relative risk for blacks: 0.69; relative risk for Latinos: 0.58). They were more
      likely to have home nebulizers. Other processes of asthma care, including ratings
      of providers and asthma care, use of written management plans, use of preventive
      visits and specialists, and having no pets or smokers at home, were equal or
      better for minority children compared with white children. CONCLUSIONS: Black and
      Latino children had worse asthma status and less use of preventive asthma
      medications than white children within the same managed Medicaid populations.
      Most other processes of asthma care seemed to be equal or better for minorities
      in the populations that we studied. Increasing the use of preventive medications
      is a natural focus for reducing racial disparities in asthma.

PMID- 11986448
TI  - Nebulized budesonide inhalation suspension compared with cromolyn sodium
      nebulizer solution for asthma in young children: results of a randomized outcomes
      trial.
AB  - OBJECTIVE: The availability of antiinflammatory asthma medications for infants
      and young children has been limited. The objective of this study was to compare
      effects of nebulized budesonide inhalation suspension and cromolyn sodium
      nebulizer solution on asthma-related health outcomes in young children with
      asthma. METHODS: We conducted a randomized, parallel-group, 52-week, open-label
      study in 36 US clinical sites. Patients included 335 children who were 2 to 6
      years of age and had persistent asthma that had been treated with at least 1 long
      term control medication; 287 children (86%) completed the study. Patients
      received budesonide inhalation suspension, 0.5 mg daily (n = 168), or cromolyn
      sodium nebulizer solution, 20 mg 4 times daily (n = 167), for 8 weeks, followed
      by dose titration at the investigator's discretion. The main outcome measure was
      the rate of asthma exacerbations over 52 weeks. Secondary measures included times
      to first asthma exacerbation and first use of additional asthma therapy, asthma
      symptom scores, rescue medication use, and health care resource use. RESULTS: The
      budesonide group had a mean (median) asthma exacerbation rate of 1.23 (0.99) per
      year compared with 2.41 (1.85) for the cromolyn group, significantly longer times
      to first exacerbation and first use of additional long-term asthma medication,
      greater improvements in asthma symptom scores, reduced use of rescue medication,
      and fewer urgent care visits. Both treatments were well tolerated. CONCLUSIONS:
      Budesonide inhalation suspension was more effective than nebulized cromolyn
      sodium in young children with persistent asthma. Both treatments were well
      tolerated with similar adverse event profiles.

PMID- 11986449
TI  - Reduced risk of sudden death from chest wall blows (commotio cordis) with safety
      baseballs.
AB  - OBJECTIVES: In an experimental model of sudden death from baseball chest wall
      impact (commotio cordis), we sought to determine if sudden death by baseball
      impact could be reduced with safety baseballs. BACKGROUND: Sudden cardiac death
      can occur after chest wall impact with a baseball (commotio cordis). Whether
      softer-than-standard (safety) baseballs reduce the risk of sudden death is
      unresolved from the available human data. In a juvenile swine model, ventricular
      fibrillation (VF) has been shown to be induced reproducibly by precordial impact
      with a 30-mph baseball 10 to 30 ms before the T-wave peak, and this likelihood
      was reduced with the softest safety baseballs (T-balls). To further test whether
      safety baseballs would reduce the risk of sudden death at velocities more
      relevant to youth sports competition, we used our swine model of commotio cordis
      to test baseballs propelled at the 40-mph velocity commonly attained in that
      sport. METHODS: Forty animals received up to 3 chest wall impacts at 40 mph
      during the vulnerable period of repolarization for VF with 1 of 3 different
      safety baseballs of varying hardness, and also by a standard baseball. RESULTS:
      Safety baseballs propelled at 40 mph significantly reduced the risk for VF. The
      softest safety baseballs triggered VF in only 11% of impacts, compared with 19%
      and 22% with safety baseballs of intermediate hardness, and 69% with standard
      baseballs. CONCLUSION: In this experimental model of low-energy chest wall
      impact, safety baseballs reduced (but did not abolish) the risk of sudden cardiac
      death. More universal use of these safety baseballs may decrease the risk of
      sudden death on the playing field for young athletes.

PMID- 11986450
TI  - Serial assessment of mortality in the neonatal intensive care unit by algorithm
      and intuition: certainty, uncertainty, and informed consent.
AB  - OBJECTIVES: Does predictive power for outcomes of neonatal intensive care unit
      (NICU) patients get better with time? Or does it get worse? We determined the
      predictive power of Score for Neonatal Acute Physiology (SNAP) scores and
      clinical intuitions as a function of day of life (DOL) for newborn infants
      admitted to our NICU. METHODS: We identified 369 infants admitted to our NICU
      during 1996-1997 who required mechanical ventilation. We calculated SNAP scores
      on DOL 1, 3, 4, 5, 7, 10, 14, 21, 28, and weekly thereafter until either death or
      extubation. We also asked nurses, residents, fellows, and attendings on each day
      of mechanical ventilation: "Do you think this child is going to live to go home
      to their family, or die before hospital discharge?" RESULTS: Two thousand twenty
      eight SNAP scores were calculated for 285 infants. On DOL 1, SNAP for
      nonsurvivors (24 +/- 8.7 [standard deviation]) was significantly higher than SNAP
      for survivors (13 +/- 6.1). However, this difference diminished steadily and by
      DOL 10 was no longer statistically significant (12.7 +/- 4.9 vs 10.0 +/- 4.8). On
      each NICU day, at all ranges of SNAP scores, there were at least as many infants
      who would ultimately survive as would die. Consequently, the positive predictive
      value of any SNAP value for subsequent mortality was <0.5 on all NICU days.
      Prediction profiles were obtained for 230 ventilated infants reflecting over 11
      000 intuitions obtained on 2867 patient days. One hundred fifty-seven (81%) of
      192 survivor profiles displayed consistent accurate prediction profiles-at least
      90% of their NICU ventilation days were characterized by 100% prediction of
      survival. Twenty-five (13%) of 192 surviving infants survived somewhat
      unexpectedly; that is, after at least 1 day characterized by at least 1 estimate
      of "death." Thirty-three (60%) of the 55 nonsurvivors died before DOL 10. Eighty
      two percent of the prediction profiles for these early dying infants were
      homogeneous, dismal, and accurate. Twenty-two (40%) of the 55 nonsurvivors died
      after DOL 10. Seventeen (78%) of these 22 late-dying infants were predicted to
      live by many observers on many hospital days. Sixty-one (30%) of 230 profiled
      patients had at least 1 NICU day characterized by at least 1 prediction of death;
      26/61 (43%) of these patients were incorrectly predicted; that is, they survived.
      Seventeen infants who were predicted to die during but survived nonetheless were
      assessed neurologically at 1 year. Fourteen (82%) of these 17 were not
      neurologically normal-8 were clearly abnormal, 1 suspicious, and 5 had died.
      CONCLUSIONS: If absolute certainty about mortality is the only criterion that can
      justify a decision to withhold or withdraw life-sustaining treatment in the NICU,
      these data would make such decisions difficult on the first day of life, and
      increasingly problematic thereafter. However, if we acknowledge that medicine is
      inevitably an inexact science and that clinical predictions can never be perfect,
      we can ask the more interesting question of whether good but less-than-perfect
      predictions of imprecise but ethically relevant clinical outcomes can still be
      useful. We think that they can-and that they must.

PMID- 11986451
TI  - Characteristics of deaths occurring in children's hospitals: implications for
      supportive care services.
AB  - CONTEXT: End-of-life care is an important yet underdeveloped component of
      pediatric hospital services. OBJECTIVES: We sought 1) to describe the
      demographics of children who die in children's hospitals, 2) to describe the
      prevalence of complex chronic conditions (CCCs) among these cases, and 3) to test
      the hypotheses that cases with a greater number of CCC diagnoses experience
      longer periods both of mechanical ventilation and of hospitalization before
      death. Design and Methods. We identified all deaths of patients 0 to 24 years old
      that occurred in the 60 hospitals contributing discharge data to the National
      Association of Children's Hospitals and Related Institutions data consortium for
      the years 1991, 1994, and 1997. We classified discharge diagnoses into 9 major
      categories of CCCs (cardiovascular, neuromuscular, malignancy, respiratory,
      renal, metabolic, gastrointestinal, hematologic/immunologic, and other
      congenital/genetic). RESULTS: Of the 13 761 deaths identified, 42% had been
      admitted between 0 and 28 days of life, 18% between 1 and 12 months, 25% between
      1 and 9 years, and 15% between 10 and 24 years. Fifty-three percent were white,
      20% were black, and 9% were Hispanic. The principal payer was listed as a
      governmental source for 42% and a private insurance company for 35%. Based on all
      the discharge diagnoses recorded for each case, 40% had no CCC diagnosis, 44% had
      diagnoses representing 1 major CCC category, 13% had diagnoses representing 2 CCC
      categories, and 4% had diagnoses representing 3 or more CCC categories. Among
      cases that had no CCC diagnoses, the principal diagnoses were related to
      prematurity and newborn disorders for 32% of these cases, injuries and poisoning
      for 26%, and an assortment of acute and infectious processes for the remaining
      42%. Mechanical ventilation was provided to 66% of neonates, 40% of infants, 36%
      of children, and 36% of adolescents. Cases with CCCs were more likely than non
      CCC cases to have been mechanically ventilated (52% vs 46%), and to have been
      ventilated longer (mean: 11.7 days for CCC cases vs 4.8 days for non-CCC cases).
      The median duration of hospitalization was 4 days, while the mean was 16.4 days.
      After adjustment for age, sex, year, and principal payer, compared with patients
      with no CCC diagnoses, those with 1 major CCC category had a significantly lower
      hazard of dying soon after admission (hazard ratio [HR]: 0.60; 95% confidence
      interval [CI]: 0.57-0.62), those with 2 CCC categories even lower (HR: 0.53; 95%
      CI: 0.50-0.57), and those with 3 or more CCC categories the lowest hazard of
      rapid death (HR: 0.51; 95% CI: 0.46-0.57). This trend of diminishing hazard of
      rapid death was significant across the 3 groups of children with 1 or more CCCs.
      CONCLUSIONS: Children's hospitals care for a substantial number of dying
      patients, who differ widely by age and medical conditions. Children who die in
      the hospital with CCCs are more likely to experience longer periods of mechanical
      ventilation and hospitalization before death.

PMID- 11986452
TI  - A randomized, clinical trial of oral midazolam plus placebo versus oral midazolam
      plus oral transmucosal fentanyl for sedation during laceration repair.
AB  - OBJECTIVE: To determine whether a combination of oral transmucosal fentanyl
      (Fentanyl Oralet, Abbott Laboratories, North Chicago, IL) plus oral midazolam has
      an acceptable safety profile and is more effective than oral midazolam alone for
      sedation during laceration repair in a pediatric emergency department (ED).
      METHODS: Randomized, double-blind, placebo-controlled, clinical trial. Patients
      between 2 and 8 years of age who weighed >10 kg and presented to the ED with a
      laceration in need of repair under sedation were eligible for inclusion. All
      patients received oral midazolam (0.5 mg/kg; maximum dose 10 mg) and either
      fentanyl (5-10 microg/kg) or placebo in oralet form. Data collected every 5
      minutes included the following: heart rate, oxygen saturation, respiratory rate,
      pain as measured on a Children's Hospital of Eastern Ontario Pain Score (CHEOPS)
      scale (range: 4-13), and an activity scale (range: 1-5). Effectiveness of
      sedation was measured by CHEOPS and activity scores compared between the
      treatment groups. RESULTS: Fifty-one patients were randomized to receive oral
      midazolam plus fentanyl (N = 28) or oral midazolam plus placebo (N = 23). Age,
      weight, gender, or baseline pain and activity scores did not differ between the 2
      groups. Seven patients in the fentanyl group vomited compared with 0 patients in
      the placebo group. Three patients in the fentanyl group and no patients in the
      placebo group had brief oxygen saturation below 93% on room air. The mean pain
      score within 5 minutes of the start of the procedure did not differ between the 2
      groups (fentanyl group, 9.4 versus placebo group, 8.8). Mean activity scores
      within 5 minutes of the start of the procedure were also similar (fentanyl group,
      4.3 versus placebo group, 4.3). CONCLUSIONS: The addition of oral transmucosal
      fentanyl to oral midazolam did not improve pain or activity scores in pediatric
      patients given sedation for laceration repair. Patients who received Fentanyl
      Oralet suffered significantly more side effects despite the relatively low doses
      administered in this study. Oral transmucosal fentanyl should not be used for
      procedural sedation in the ED.

PMID- 11986453
TI  - Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young
      children.
AB  - Intervention trials have shown that zinc is efficacious in treating acute
      diarrhea in children of developing countries. In a randomized, placebo-controlled
      trial, we assessed the effectiveness and efficacy of giving 3 Recommended Daily
      Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea.
      METHODS: Seventeen hundred ninety-two cases of acute diarrhea in Nepalese
      children were randomized to 4 study groups. Three groups were blinded and the
      children supplemented daily by field workers with placebo syrup, zinc syrup, or
      zinc syrup and a massive dose of vitamin A at enrollment. The fourth group was
      open and the caretaker gave the children zinc syrup daily. Day-wise information
      on morbidity was obtained by household visits every fifth day. RESULTS: The
      relative hazards for termination of diarrhea were 26% (95% confidence interval
      [CI]: 8%, 46%), 21% (95% CI: 4%, 38%), and 19% (95% CI: 2%, 40%) higher in the
      zinc, zinc-vitamin A, and zinc-caretaker groups, respectively, than in the
      placebo group. The relative risks of prolonged diarrhea (duration >7 days) in
      these groups were 0.57 (95% CI: 0.38, 0.86), 0.53 (95% CI: 0.35, 0.81), and 0.55
      (0.37, 0.84); zinc accordingly reduced the risk of prolonged diarrhea with 43% to
      47%. Five percent and 5.1% of all syrup administrations were followed by
      regurgitation in the zinc and zinc-vitamin A group, respectively, whereas this
      occurred after only 1.3% of placebo administrations. Vomiting during diarrhea was
      also more common in children receiving zinc. CONCLUSIONS: Three Recommended Daily
      Allowances of zinc given daily by caretakers or by field workers substantially
      reduced the duration of diarrhea. The effect of zinc was not dependent on or
      enhanced by concomitant vitamin A administration.

PMID- 11986454
TI  - Occurrence of omphalocele in relation to maternal multivitamin use: a population
      based study.
AB  - OBJECTIVE: We evaluated the association between mothers' use of multivitamin
      supplements and their infants' risk for omphalocele, a congenital anomaly of the
      abdominal wall. Omphalocele can occur in certain multiple congenital anomaly
      patterns with neural tube defects, for which a protective effect of multivitamins
      with folic acid has been demonstrated. METHODS: We used data from a population
      based case-control study of infants born from 1968-1980 to mothers residing in
      metropolitan Atlanta. Case-infants with nonsyndromic omphalocele (n = 72) were
      actively ascertained from multiple sources. Control-infants (n = 3029), without
      birth defects, were selected from birth certificates by stratified random
      sampling. RESULTS: Compared with no use in the periconceptional period,
      periconceptional use of multivitamin supplements (regular use from 3 months
      before pregnancy through the first trimester of pregnancy) was associated with an
      odds ratio for nonsyndromic omphalocele of 0.4 (95% confidence interval [CI]: 0.2
      1.0). For the subset comprising omphalocele alone or with selected midline
      defects (neural tube defects, hypospadias, and bladder/cloacal exstrophy), the
      odds ratio was 0.3 (95% CI: 0.1-0.9). These estimates were similar when the
      reference group also included women who began using multivitamins late in
      pregnancy (during the second or third month of pregnancy). The small number of
      participants limited the precision of subgroup analyses and translated into wide
      confidence intervals that included unity. CONCLUSIONS: Periconceptional
      multivitamin use was associated with a 60% reduction in the risk for nonsyndromic
      omphalocele. These findings await replication from additional studies to confirm
      the findings, generate more precise estimates, and detail possible mechanisms of
      actions.

PMID- 11986455
TI  - Adverse clinical outcomes associated with short stature at dialysis initiation: a
      report of the North American Pediatric Renal Transplant Cooperative Study.
AB  - OBJECTIVE: We examined whether height less than the 1% for age (z score <-2.5) at
      dialysis initiation predicts adverse clinical outcomes for children with kidney
      failure. DESIGN: National cohort study of children initiating dialysis, followed
      for a minimum of 1 month to a maximum of 8 years. SETTING: Voluntary consortium
      of pediatric nephrology centers across the United States and Canada in the North
      American Pediatric Renal Transplant Cooperative Study. PATIENTS: Two thousand
      three hundred six patients </=21 years old initiated on dialysis between 1992 and
      2000. Outcome Measures. School attendance, transplant wait listing,
      hospitalization rates, and survival. RESULTS: Although there were no differences
      in transplant wait listings, school-aged children with short stature were less
      likely to be attending school full-time than were their counterparts with more
      normal height, even if medically capable. Short-stature patients have
      significantly more hospital days per month of dialysis follow-up than those
      patients with better growth (mean: 1.92 vs 1.58; median: 0.73 vs 0.44 hospital
      days per month of follow-up). Cox proportional hazards regression analyses show
      that children with height <1% for age have a twofold higher risk of death than
      those with more normal height, even after controlling for patient age, race,
      gender, cause of end-stage renal disease, wait list status, and dialysis
      modality. CONCLUSIONS: Poor growth during chronic renal insufficiency leading to
      short stature at dialysis initiation is a marker for a more complicated clinical
      course for children with kidney failure. Aggressive nutritional support and early
      referral to a nephrologist to optimize growth may improve long-term outcomes for
      children with chronic kidney disease.

PMID- 11986456
TI  - Hirschsprung's disease: a review.

PMID- 11986457
TI  - Improving childhood asthma outcomes in the United States: a blueprint for policy
      action.
AB  - BACKGROUND/OBJECTIVE: Asthma is increasingly being recognized as an important
      public health concern for children in the United States. Effective management of
      childhood asthma may require not only improving guideline-based therapeutic
      interventions, but also addressing social and physical environmental risk
      factors. The objective of this project was to create a blueprint for improvement
      of national policy in this area. DESIGN/METHODS: A nominal group process with
      nationally recognized experts and leaders (referred to as "the committee") in
      childhood asthma. RESULTS: The committee identified 11 policy recommendations
      (numbered in order below) in 2 broad categories: Improving Health Care Delivery
      and Financing, and Strengthening the Public Health Infrastructure.
      Recommendations regarding Improving Health Care Delivery and Financing include
      the development and implementation of quality-of-care standards in 1) primary
      care, 2) self-management education, and 3) case-management interventions, and the
      expansion of insurance coverage and benefit design by 4) extending continuous
      health insurance coverage for all children, 5) developing model insurance
      benefits packages for essential childhood asthma services, and 6) educating
      health care purchasers in how to use them. Recommendations for Strengthening the
      Public Health Infrastructure include public funding of asthma services that fall
      outside the insurance system through establishing 7) public health grants to
      foster asthma-friendly communities and 8) school-based asthma initiatives. 9)
      Launching a national asthma public education campaign, 10) developing a national
      asthma surveillance system, and 11) establishing a national agenda for asthma
      prevention research, with an emphasis on epidemiologic and behavioral sciences,
      are also recommended. CONCLUSIONS: Implementing these recommendations will
      require coordination of activities at the national, state, and local community
      level, and within and outside the health care delivery system. With a further
      commitment of national and local resources, implementation of these
      recommendations will likely lead to improved child and family asthma outcomes in
      the United States. childhood asthma, health care policy, health care services.

PMID- 11986458
TI  - Unique features of infective endocarditis in childhood.

PMID- 11986459
TI  - Diagnosing celiac disease in 2002: who, why, and how?

PMID- 11986460
TI  - "You've got mail": issues in communicating with patients and their families by e
      mail.

PMID- 11986461
TI  - Probiotics in pediatrics.

PMID- 11986462
TI  - Chronic lung disease after activated charcoal aspiration.
AB  - The ingestion of toxic substances is a common pediatric emergency. Activated
      charcoal is part of the standard treatment for most toxic ingestions and is
      considered a benign therapy. We report a case of inadvertent administration of
      activated charcoal into the trachea that resulted in the development of chronic
      lung disease.

PMID- 11986463
TI  - Is it more than just constipation?
AB  - We report an infant presenting with constipation, whose history and physical
      examination initiated the investigation that led to the diagnosis of the
      Currarino triad in the proband and 2 other family members.

PMID- 11986464
TI  - Diffuse alveolar hemorrhage in pediatric hematopoietic cell transplant patients.
AB  - OBJECTIVE: Diffuse alveolar hemorrhage (DAH) is defined as a syndrome of hypoxia,
      dyspnea, infiltrates on chest radiograph, and bloody fluid on successive
      bronchoalveolar lavages without apparent infection. Minimal experience has been
      reported with DAH after hematopoietic cell transplant (HCT) in children. We
      reviewed the incidence, management and outcome of DAH in a pediatric HCT
      population. METHODS: Retrospective review of 138 patients undergoing allogeneic
      (n = 89) or autologous (n = 49) HCT at a referral children's medical center
      between January 1996 and April 2000. RESULTS: Seven (5.1%) of 138 patients met
      criteria for DAH; all were allogeneic recipients. Mean age of DAH patients was 11
      years (range: 1.4-15.2). Median onset of DAH following HCT was day 24 (range: 10
      50), median day of engraftment day 20 and white blood cell count 0.54 x 10(9)/L
      (range: < 0.1-7.03), with no difference between survivors and nonsurvivors. All
      patients developed clinical respiratory failure and 6 required intubation, with
      PaO(2)/fraction of inspired oxygen <200. Patients were intubated a median of 12
      days (range: 1-75). All patients experienced >1 episode of bleeding and 3
      patients required reintubation after successful extubation resulting from
      recurrent DAH. Bronchoalveolar lavage fluid cultures were negative for viruses,
      bacteria and fungi. All DAH patients received steroids. Three patients died with
      progressive pulmonary failure and other organ system involvement. Four of 7 DAH
      patients (57%) survived to discharge, but 3 died from disease relapse at days
      116, 138, and 273 post-HCT. CONCLUSION: DAH occurred more frequently in
      allogeneic HCT recipients compared with autologous recipients. Onset of DAH
      coincided closely with white blood cell engraftment. Although associated with
      significant respiratory failure and need for mechanical ventilation, HCT patients
      can survive DAH.

PMID- 11986465
TI  - Late diagnosis of severe colchicine intoxication.
AB  - A 4-year-old Turkish girl was referred to our hospital with the findings of
      encephalopathy and pancytopenia. She had a history of severe abdominal cramps and
      gastrointestinal bleeding. A confused state, muscle pain and weakness, erythema
      bullous and erythema-nodosum-like skin lesions, and alopecia were observed at her
      hospitalization. All of these symptoms resolved on follow-up. On laboratory
      investigation severe thrombocytopenia and leukopenia, mild anemia, a moderate
      increase in aspartate aminotransferase and alanine aminotransferase levels were
      detected. After reevaluating her medical history, it was learned that she had
      accidentally taken 1.3 to 1.5 mg/kg of colchicine 3 to 4 days before her first
      hospitalization. The possibility of misdiagnosis of colchicine intoxication
      should be borne in mind, and pediatricians must be aware of its toxic effects,
      especially in areas where patients with familial Mediterranean fever are present.

PMID- 11986466
TI  - Guidelines for expert witness testimony in medical malpractice litigation.
      Committee on Medical Liability. American Academy of Pediatrics.
AB  - The interests of the public and the medical profession are best served when
      scientifically sound and unbiased expert witness testimony is readily available
      to plaintiffs and defendants in medical negligence suits. As members of the
      physician community, as patient advocates, and as private citizens, pediatricians
      have ethical and professional obligations to assist in the administration of
      justice, particularly in matters concerning potential medical malpractice. The
      American Academy of Pediatrics believes that the adoption of the recommendations
      outlined in this statement will improve the quality of medical expert witness
      testimony in such proceedings and thereby increase the probability of achieving
      equitable outcomes. Strategies to enforce ethical guidelines should be monitored
      for efficacy before offering policy recommendations on disciplining physicians
      for providing biased, false, or unscientific medical expert witness testimony.

PMID- 11986467
TI  - Red reflex examination in infants. Section on Ophthalmology. American Academy of
      Pediatrics.
AB  - Red reflex examination is recommended for all infants. This statement describes
      the indications for and the technique to perform this examination, including
      indications for dilation of the pupils before examination and indications for
      referral to an ophthalmologist.

PMID- 11986468
TI  - Pediatric Organ Donation and Transplantation: policy statement: organizational
      principles to guide and define the child health care system and/or improve the
      health of all children: Committee on Hospital Care and Section on Surgery.
      American Academy of Pediatrics.
AB  - Pediatric organ donation and organ transplantation can have a significant life
      extending benefit to the young recipients of these organs and a high emotional
      impact on donor and recipient families. Pediatricians should become better
      acquainted with evolving national strategies involving organ procurement and
      organ transplantation to help acquaint families with the benefits of organ
      donation and to help shape public policies that will aid in efforts to provide a
      system of procurement, distribution, and finance that is fair and equitable to
      children and adults. Major issues of concern are availability and access;
      oversight and control; pediatric medical and surgical consultation throughout the
      organ donation and transplantation process; ethical, social, financial, and
      follow-up issues; insurance coverage issues; and public awareness of the need for
      organ donors of all ages.

PMID- 11986469
TI  - Diagnostic accuracy of screening electrocardiograms in the long QT syndrome.

PMID- 11986470
TI  - Glucagon is very unlikely to have caused hyponatremia.

PMID- 11986471
TI  - Noise-induced hearing loss.

PMID- 11986472
TI  - Appendicitis-pediatric surgeons versus general surgeons.

PMID- 11986473
TI  - Absent nasal flaring in a newborn with bilateral choanal stenosis.

PMID- 11986474
TI  - FOPE II report summary and pediatric subspecialists.

PMID- 11986475
TI  - Embryonic stem cell research.

PMID- 11986476
TI  - A meta-analysis of randomized, controlled trials comparing short- and long-course
      antibiotic therapy for urinary tract infections in children.
AB  - BACKGROUND: Short-course antibiotic regimens, ranging in duration from a single
      dose to 3 days, are the current standard of care for the treatment of acute lower
      urinary tract infections (UTIs) in adult women. Despite multiple small
      randomized, controlled trials (RCTs) showing no difference in efficacy between
      short-course (</=3 days) and long-course (7-14 days) therapy in children,
      concerns about occult pyelonephritis and renal scarring have prompted standard
      recommendations of 7 to 14 days of antibiotics for UTIs in children. OBJECTIVE:
      To determine whether long-course antibiotic therapy is more effective than short
      course therapy for the treatment of UTIs in children, and to explore potential
      sources of heterogeneity in the results of existing studies. METHODS: We searched
      online bibliographic databases (Medline and Cochrane Clinical Trials Registry)
      for RCTs comparing short- and long-course therapy for the treatment of UTI in
      children, and examined the references of all retrieved articles. Candidate
      studies for meta-analysis were restricted to RCTs comparing short-course (</=3
      days) and long-course (7-14 days) outpatient therapy for acute UTI in children
      age 0 to 18 years. We excluded studies that were restricted to children with
      recurrent UTI or included children with asymptomatic bacteriuria. Sixteen studies
      met the inclusion criteria. Study quality was evaluated using a 9-item scoring
      system developed by the investigators. Data on the primary outcomes-treatment
      failure and reinfection rate-were extracted when available and reanalyzed based
      on intention to treat whenever possible. To determine whether anatomic level of
      infection (upper vs lower urinary tract) influenced the results, the meta
      analysis was repeated on the subgroup of studies that attempted to restrict their
      participants to children with lower UTI. To determine whether there was a dose
      response effect for the duration of short-course therapy, we performed separate
      subgroup analyses of studies of single-dose or single-day therapy and studies of
      3-day therapy. To explore other potential sources of study result heterogeneity,
      such as study quality and patient age, we developed a random-effects regression
      model that included these variables as covariates. RESULTS: The pooled estimate
      for the relative risk (RR) of treatment failure with short-course antibiotic
      therapy was 1.94 (95% confidence interval [CI]: 1.19-3.15) and for the RR of
      reinfection was 0.76 (95% CI: 0.39-1.47). When we excluded the 3 studies that did
      not attempt to restrict their participants to patients with lower UTI, the pooled
      RR of treatment failure was 1.74 (95% CI: 1.05-2.88) and of reinfection was 0.69
      (95% CI: 0.32-1.52). For the subgroup of studies comparing single-dose or 1-day
      therapy to long-course therapy, the pooled RR of treatment failure was 2.73 (95%
      CI: 1.38-5.40) and of reinfection was 0.37 (95% CI: 0.12-1.18). For the subgroup
      of studies comparing 3-day therapy to long-course therapy, the pooled RR of
      treatment failure was 1.36 (95% CI: 0.68-2.72) and of reinfection was 0.99 (95%
      CI: 0.46-2.13). In the meta-regression, neither study quality nor mean
      participant age was significantly associated with the odds ratio of treatment
      failure or reinfection, in either the complete set of studies or the subset of
      studies restricted to patients with lower UTI. CONCLUSIONS: In pooled analyses of
      published studies comparing long- and short-course antibiotic treatment of UTI in
      children, long-course therapy was associated with fewer treatment failures
      without a concomitant increase in reinfections, even when studies including
      patients with evidence of pyelonephritis were excluded from the analysis. Until
      there are more accurate methods for distinguishing upper from lower UTI in
      children, no additional comparative trials are warranted and clinicians should
      continue to treat children with UTI for 7 to 14 days.

PMID- 11986477
TI  - How should a fever mercury thermometer be disposed of ? A survey of those likely
      to be asked.
AB  - The American Academy of Pediatrics' recent technical report entitled "Mercury in
      the Environment: Implications for Pediatricians" was widely reported on by the
      news media. After the media reports, the New Jersey Poison Information and
      Education System experienced a notable increase in the volume of calls on this
      topic. We surveyed local, county, and state health officers who would likely be
      contacted by citizens with the question: "How should a fever mercury thermometer
      be disposed of?" Our initial contacts with health officers corroborated our
      caller's account: a lack of uniformity of response. This led us to question if
      there was any consensus in advice being offered to the public at large.

PMID- 11986478
TI  - Alcohol, breastfeeding, and development at 18 months.
AB  - OBJECTIVE: We aimed to replicate a previous study of 1-year-olds that reported a
      deficit in motor development associated with moderate alcohol use during
      lactation, using a different but comparable population. METHODOLOGY: The mental
      development of 915 18-month-old toddlers from a random sample of a longitudinal
      population-based study in the United Kingdom was measured using the Griffiths
      Developmental Scales. Frequent self-administered questionnaires during and after
      pregnancy provided maternal data. The dose of alcohol available to the lactating
      infant was obtained by multiplying the alcohol intake of the mother by the
      proportion of breast milk in the infant's diet. We compared this dose with the
      Griffiths Scales of Mental Development, taking into account potentially
      confounding variables. RESULT: Three of the Griffiths scales increased slightly
      but significantly with increasing infant alcohol exposure; there was no
      association in the remaining 2 or average of the scales. DISCUSSION: We were
      unable to replicate the earlier deficit in motor skills associated with lactation
      alcohol use. One reason may be that the dose of alcohol reaching the lactating
      infant is small, and tests of infants and toddlers have limited ability to pick
      up small effects. Studies of older children may resolve the question of the
      safety of drinking while nursing.

PMID- 11986479
TI  - Left ventricular structure and function in obese adolescents: relations to
      cardiovascular fitness, percent body fat, and visceral adiposity, and effects of
      physical training.
AB  - OBJECTIVE: Little is known about the relations of fitness and fatness to left
      ventricular structure and function in obese adolescents. This project had 2
      purposes: 1) to determine the correlations of cardiovascular fitness and
      adiposity to left ventricular parameters in obese adolescents; and 2) to see the
      effect of 8 months of physical training (PT) at low and high intensities. DESIGN:
      Obese 13- to 16-year-olds (N = 81) were tested at baseline and then randomly
      assigned to lifestyle education (LSE) alone, LSE plus moderate-intensity PT, or
      LSE plus high-intensity PT. Follow-up testing was conducted 8 months later.
      Because no significant differences were found between moderate-intensity and high
      intensity PT, the groups were combined to form a LSE + PT group. INTERVENTION:
      Eight months of PT, offered 5 days per week with the target energy expenditure
      for all PT participants being 250 kcal/session, and LSE every 2 weeks. Outcome
      Measures. Left ventricular mass divided by height to the 2.7th power
      (LVM/Ht(2.7)), midwall fractional shortening (MFS), and relative wall thickness
      (RWT) were measured using M-mode echocardiography. Cardiovascular fitness was
      measured by a maximal multistage treadmill test; percent body fat (%BF) with dual
      energy radiograph absorptiometry; and visceral adipose tissue (VAT) with magnetic
      resonance imaging. RESULTS: At baseline, high levels of VAT were associated with
      higher RWT (r = 0.30) and lesser MFS (r = -0.29). Compared with the LSE-alone
      group, the LSE + PT group significantly improved in cardiovascular fitness and
      decreased in %BF and VAT. However, there were no significant differences between
      groups on changes in LVM/Ht(2.7), MFS, or RWT. Individual changes in
      cardiovascular fitness, %BF, and VAT did not correlate significantly with
      interindividual changes in left ventricular structure and function. CONCLUSIONS:
      High levels of VAT were associated with unfavorable left ventricular structure
      and function. However, no evidence was provided that an 8-month PT program, which
      improved cardiovascular fitness and reduced general and visceral adiposity,
      improved left ventricular structure and function. Future studies consisting of
      longer training programs and/or greater weight reductions are needed to see
      whether the adverse left ventricular effects of obesity can be ameliorated by
      exercise training.

PMID- 11986480
TI  - Osteonecrosis of the hip (Legg-Calve-Perthes disease) in human immunodeficiency
      virus-infected children.
AB  - OBJECTIVE: Osteonecrosis of the hip has been reported in human immunodeficiency
      virus (HIV)-infected adults; whether this is related to HIV infection or its
      treatment is unknown. There has been 1 report of osteonecrosis among HIV-infected
      children. Specifically, avascular necrosis of the hip consistent with Legg-Calve
      Perthes disease (LCPD) was reported in 3 HIV-infected children with AIDS from
      Spain in 1992. We evaluated the prevalence and incidence of LCPD, the pediatric
      equivalent of adult osteonecrosis of the hip, in HIV-infected children
      participating in a prospective cohort study of long-term outcomes in HIV-infected
      and HIV-exposed children-Pediatric AIDS Clinical Trials Group (PACTG) protocol
      219. METHODS: PACTG 219 enrolled 2014 HIV-infected and 849 HIV-exposed,
      uninfected children between April 1993 and September 2000. Children had periodic
      examinations with collection of clinical and laboratory data. The database was
      reviewed for reports of LCPD and other bone disorders. A prevalent case was
      defined as LCPD diagnosis preceding PACTG 219 enrollment and an incident case had
      to have occurred between enrollment and September 2000. A case-control study
      (matching on age, gender, and race/ethnicity, which are known to be associated
      with risk of LCPD and HIV infection status) was performed to investigate factors
      possibly associated with LCPD. RESULTS: Six cases of LCPD (4 prevalent cases
      reported at study entry; 2 diagnosed during 5837 person-years of follow-up) were
      observed; LCPD was seen only in children with perinatal HIV infection. LCPD
      prevalence was 199 per 100 000 compared with an estimated general pediatric
      population prevalence of 23 per 100 000. Based on age-adjusted general population
      rates, the expected number of prevalent cases at PACTG 219 study entry would have
      been 0.44; the age-adjusted LCPD prevalence rate ratio was 9.0 (95% confidence
      interval [CI]: 8.3-9.7) for HIV-infected children compared with the general
      population. LCPD incidence was 34 per 100 000 person-years (95% CI: 0.42-124)
      compared with the estimated general population incidence of 6 per 100 000 person
      years (95% CI: 5-7). Based on age-adjusted general population rates, the expected
      incidence of LCPD in PACTG 219 would have been 0.42; the age-adjusted relative
      risk of LCPD in HIV-infected PACTG 219 children was 4.8 (95% CI: 0.56-10.4). No
      cases were observed in uninfected children during 1919 person-years of follow-up
      on PACTG 219; the age-adjusted expected number of cases was 0.09. Median onset
      age was 7 years; 67% were of Hispanic or black race/ethnicity and 33% were
      female. Four of the 6 LCPD cases had received antiretroviral therapy before
      diagnosis; treatment was primarily with nucleoside reverse transcriptase
      inhibitors, and 2 had received protease inhibitors. Three of the LCPD cases had
      corticosteroid exposure before the diagnosis, but only 1 child had systemic
      exposure and the remaining 2 had topical exposure exclusively. In the case
      control study, antiretroviral and corticosteroid therapy, CD4 cell percentage,
      birth weight, height for age and gender percentile, and triglyceride levels were
      not significantly associated with LCPD. However, the case-control study had
      limited power to evaluate possible associations. CONCLUSION: Similar to HIV
      infected adults, children with perinatal HIV infection have an increased risk for
      osteonecrosis of the hip, and clinicians should be alert to this diagnosis when
      HIV-infected children present with limp or hip pain. Whether LCPD is attributable
      to HIV infection itself, HIV-associated complications that could predispose to
      hypercoagulopathy, HIV-related therapies, or to the growth abnormalities in HIV
      infected children is unknown and deserves additional evaluation.

PMID- 11986481
TI  - Caloric intake and eating behavior in infants and toddlers with cystic fibrosis.
AB  - OBJECTIVE: Infants and toddlers with cystic fibrosis (CF) are at risk for poor
      growth. Controlled behavioral assessment studies have not focused on this
      population. This study compared calorie intake, percentage of Recommended Daily
      Allowance (RDA) per day and per kilogram, and percentage of calories from fat,
      protein, and carbohydrates between infants and toddlers with CF and healthy
      peers. Also, eating behaviors, such as meal duration, bites and sips per minute,
      percentage of meal spent eating, children's problematic eating behaviors, and
      parents' perceptions of mealtime behaviors were compared between infants and
      toddlers with CF and controls. Five hypotheses were tested. 1) Infants and
      toddlers with CF would be comparable to controls on the number of calories
      consumed per day and the percentage of calories from fat. 2) Infants and toddlers
      with CF would not meet the CF dietary guidelines for the percentage of RDA for
      calories or the percentage of calories from fat. 3) Infants and toddlers with CF
      would have longer meal durations than healthy peers, but would not differ on the
      pace of eating, the number of calories consumed during the meal, or the
      percentage of time spent eating during the meal. 4) Parents of infants and
      toddlers with CF would perceive more problematic mealtime behavior than controls.
      5) Parents' perceptions of children's mealtime behavior would positively
      correlate with meal duration and negatively correlate with the number of calories
      consumed during the meal. DESIGN: A 2-group comparison study. SETTING/SAMPLE: A
      clinical sample of 35 infants and toddlers with CF (M = 18.6; standard deviation
      = 8.1 months; range = 7-35 months) and a community sample of 34 healthy peers
      matched for age, gender, socioeconomic status, and number of parents and siblings
      present during mealtimes. MEASUREMENT AND MAIN RESULTS: Children's calorie intake
      was measured using 3-day diet diaries. The 2 groups did not differ on the total
      number of calories consumed per day, the percentage of calories derived from fat,
      or the percentage of RDA consumed per day. Infants and toddlers with CF were not
      meeting the CF dietary recommendations of 120% to 150% RDA for energy with 40% of
      calories coming from fat. Using the Dyadic Interaction Nomenclature for Eating, a
      behavioral coding system, videotaped recordings of children's dinner meals were
      scored for meal duration, number of bites and sips per minute, number of calories
      per bite or sip, and the percentage of 10-second intervals with bites and sips.
      The CF sample had significantly longer mealtimes (20.2 minutes) than the control
      group (16.4 minutes), but did not differ on calories consumed at the meal, bites
      and sips per minute, calories per bite and sip, or time spent eating during the
      meal. On the Behavioral Pediatrics Feeding Assessment Scale, a measure of
      parental perceptions of mealtime behavior that was completed by a subset of
      families (39 families), parents of infants and toddlers with CF endorsed a
      greater number of mealtime behaviors as problems and a higher occurrence of
      problems than did parents of controls. Examples of these behaviors for the CF
      sample included problems with their child's willingness to try new foods (48%),
      eat vegetables (48%), and observations that their child has a poor appetite (32%)
      and would rather drink than eat (32%). Parents of children with CF chose a
      greater number of mealtime strategies and feelings as problems and reported more
      frequently using problematic strategies at mealtimes than did parents of
      controls. Examples of problematic strategies and feelings for parents of infants
      and toddlers with CF included feeling anxious/frustrated when feeding their
      children (37%), not feeling confident that their child eats enough (32%), and
      using coaxing to get their child to take a bite (26%). For the entire sample, a
      positive correlation of 0.29 was found between the number of mealtime behavior
      problems reported by parents and meal duration, suggesting the co-occurrence of
      problematic mealtime behavior with longer meal duration. No relationship was
      found between the number of child mealtime behavior problems reported by parents
      and the number of calories consumed during the filmed meal. For the CF sample, a
      correlation of -0.26 between children's weight percentile for age and the filmed
      meal duration was found, suggesting a tendency for meal duration to increase as
      children's weight for age decreases. Post-hoc analyses were conducted comparing
      infants and toddlers with previously reported samples of preschool and school
      aged children on meal duration. Results demonstrated that in each group, children
      with CF had longer meals than age-matched controls. CONCLUSIONS: Our findings
      reveal significant deficits in achieving dietary recommendations for many
      families of infants and toddlers with CF. Only 11% of infants and toddlers with
      CF met the CF dietary recommendation of at least 120% of the RDA/day for energy.
      In addition, infants and toddlers were found to derive only 34% of their daily
      calories from fat, compared with the recommended 40% needed for a moderate to
      high fat diet. These results underscore the need for intervention in families of
      infants and toddlers with CF, who in addition to being at increased risk for
      malnutrition, may also experience a hastening in the decline of their pulmonary
      status because of poor nutritional status. Currently, there is limited
      programmatic research on nutritional and feeding interventions for toddlers and
      infants with CF. One study, which used a hospital-based behavioral education
      program to increase the caloric intake of 3 children (ages 10-20 months) who were
      below the fifth percentile for weight for length, found at least a 54% increase
      in calories for each child after treatment. Similarly, preliminary findings of 2
      parent-based interventions, a nutrition education curriculum and a nutrition
      education plus behavior parent-training curriculum, found a 22% and 32% increase
      in daily calories, respectively, at treatment completion. A large-scale clinical
      trial is needed to evaluate the efficacy of any nutritional intervention before
      widespread dissemination. Additional assessment-focused research is also needed
      to identify patients' who may be at greatest risk for malnutrition and to guide
      the development of interventions to treat them.

PMID- 11986482
TI  - An English-language clinic-based literacy program is effective for a multilingual
      population.
AB  - OBJECTIVE: To assess the effectiveness of a clinic-based pediatric literacy
      intervention on a multilingual population. BACKGROUND: Clinic-based literacy
      interventions are effective among English- and Spanish-speaking children. No data
      exist for multilingual populations. SETTING: Pediatric clinic in an urban county
      hospital. Design/Methods. Reading practices of 2 cross-sectional groups were
      assessed by standardized interview before and after the intervention. The
      intervention consisted of waiting-room volunteers reading to children, literacy
      counseling, and gift of a children's book at each well-child visit from 6 months
      to 5 years. Outcomes were assessed separately for primary English-speaking and
      primary non-English-speaking families. RESULTS: The baseline (N=85) and
      postintervention (N=95) groups were similar with respect to child age and sex,
      parental education, and length of time in the United States. Fourteen languages
      were represented in total, the most common being English (41%), Somali (28%),
      Spanish (9%), Vietnamese (7%), Oromo (3%), and Tigrinyan (3%). Compared with
      baseline, postintervention respondents were more likely to report reading as a
      favorite activity for the child (10% vs 25%) and parent (18% vs 40%), to read to
      their child before bed at least weekly (45% vs 71%), and to possess over 10
      children's books at home (49% vs 63%). Among English-speaking families (N=30
      baseline, N=40 postintervention), weekly bedtime reading increased (63% to 93%),
      reading as child's favorite activity increased (7% vs 30%), and reading as the
      parent's favorite activity to do with child increased (33% vs 58%). The
      proportion of English-speaking families possessing over 10 books at home and
      those reading with their children at least weekly showed no difference between
      the baseline and postintervention groups. Among non-English-speaking families
      (N=55 baseline, N=55 postintervention), weekly bedtime reading increased (36% vs
      56%), reading as the parent's favorite activity increased (11% vs 27%), and the
      number of families to possess >10 children's books in the home increased (31% vs
      49%). Reading as child's favorite activity (13% vs 24%) and weekly book sharing
      (60% vs 76%) showed nonsignificant trends between the non-English-speaking
      baseline and postintervention groups. CONCLUSIONS: This clinic-based literacy
      intervention influences home literacy behavior in this multiethnic setting, in
      both English-speaking and non-English-speaking families. Although efforts should
      be made to make such programs more appropriate for linguistic minorities, non
      English-speaking families do stand to benefit from English-language-oriented
      programs. literacy, Reach Out and Read, pediatrics, reading, child development.

PMID- 11986483
TI  - Ultrasonographic evaluation of cervical lymph nodes in Kawasaki disease.
AB  - OBJECTIVE: Kawasaki disease (KD) is one of the common causes of cervical
      lymphadenopathy during early childhood. The purpose of this study was to compare
      the ultrasonographic feature of cervical lymph nodes in patients with KD,
      bacterial lymphadenitis, and infectious mononucleosis. DESIGN: We studied 22
      patients with KD, 8 with presumed bacterial lymphadenitis, and 5 with Epstein
      Barr virus infectious mononucleosis. We examined the cervical nodes by
      ultrasonography using a 7.5-MHz or 10-MHz transducer of a B-mode sector scanner
      in all patients with a chief complaint of fever and a visible cervical mass
      during a fixed time interval (July 1995-March 2000). RESULTS: In KD patients,
      transverse ultrasonograms demonstrated multiple hypoechoic-enlarged nodes forming
      one palpable mass, which resembled a cluster of grapes. The ultrasonographic
      appearance of these nodes was similar in patients with acute Epstein-Barr virus
      infection, but differed from the pattern in presumed bacterial lymphadenitis.
      Five KD patients had had fever and cervical lymphadenopathy for several days
      before other manifestations of KD were noted. In these patients, it was possible
      to differentiate by ultrasonography between KD and presumed bacterial
      lymphadenitis at an early stage. CONCLUSION: Ultrasonographic features of
      cervical lymph nodes were different for KD than for presumed bacterial
      lymphadenitis. Ultrasonographic evaluation might be of value for diagnosis of KD
      patients with cervical lymphadenopathy at an early stage of the disease.

PMID- 11986484
TI  - Pneumatosis intestinalis after pediatric thoracic organ transplantation.
AB  - OBJECTIVE: To review and describe pneumatosis intestinalis (PI) in children who
      have undergone thoracic organ transplantation and evaluate potential risk
      factors. METHODS: We retrospectively reviewed abdominal radiographs obtained from
      June 1992 through September 2000 in all pediatric (age <21 years) thoracic organ
      recipients who survived at least 1 week after transplantation. In this group, a
      case was defined as an episode of radiographically confirmed PI; those without PI
      were assigned as controls. Variables analyzed included demographic data,
      gastroenteritis history (stool cultures or symptoms of gastroenteritis), and
      transplant-related factors (ie, graft type, rejection history, immunosuppression
      regimen). Significance was defined as P <.05. RESULTS: Over this 8-year period,
      PI occurred in 8 (7%) of 116 patients (0.86% annual risk). No child had >1
      diagnosed episode of PI. Of these 8 cases, 7 presented with 1 or more abdominal
      symptoms. Three of these children had rotavirus antigen isolated in their stool,
      2 others were noted to have stool positive for Clostridium difficile toxin, and
      in the other 3, no pathogen was identified. All cases were treated with a regimen
      of intravenous antibiotics and total parenteral nutrition. There were no deaths;
      however, 1 patient developed an Aspergillus pulmonary infection during his course
      of antibiotic therapy, and another underwent an exploratory laparotomy without
      bowel resection. Significant risk factors included black race (unadjusted odds
      ratio: 16), younger age at presentation (age <5 years; unadjusted odds ratio: 9),
      higher steroid dose (steroid dose >0.5 mg/kg/d; unadjusted odds ratio: 7), and a
      higher tacrolimus level at presentation (tacrolimus level >1; unadjusted odds
      ratio: 6). PI did not occur with a steroid dose <0.4 mg/kg/d. Variables not
      associated with increased risk for developing PI included gender, graft type,
      total white blood cell count, recent antibiotic use, concurrent use of an
      antimetabolite, cytomegaloviral infection, past use of extracorporeal membrane
      oxygenation, and graft rejection history. CONCLUSIONS: Significant risk factors
      for the development of PI in our pediatric thoracic organ transplantation
      population included black race, younger age, higher daily steroid dosing, and a
      high tacrolimus level at presentation. In the children diagnosed with PI, there
      were no related deaths, significant gastrointestinal sequelae, or complications.
      These findings suggest that in this population, PI will often have a benign
      course when treated aggressively, and that steroid dosing should be reduced to
      <0.5 mg/kg/d whenever possible.

PMID- 11986485
TI  - Mortality associated with congenital syphilis in the United States, 1992-1998.
AB  - OBJECTIVE: To summarize national trends in the incidence of congenital syphilis
      (CS) and associated mortality. METHODS: We analyzed CS surveillance data reported
      to the Centers for Disease Control and Prevention by 50 states and the District
      of Columbia from 1992-1998. RESULTS: From 1992-1998, 942 deaths, including 760
      stillbirths, were reported among 14 627 cases of CS, yielding a case fatality
      ratio (stillborns and deaths/all cases) of 6.4%. Untreated, inadequately treated,
      or undocumented treatment of syphilis during pregnancy accounted for 87.4% of
      reported cases. Among CS cases, there was an inverse relationship between the
      number of prenatal care visits (0, 1-4, 5-9, >/=10) and risk of fatal outcome.
      Among deaths, 52% of deliveries occurred by 30 weeks' gestation. Among live born
      infants with CS, death occurred more often in infants for whom no radiograph or
      cerebrospinal fluid evaluation was reported. Although both cases and deaths from
      CS declined from 1992-1998, there was no significant change in the case fatality
      ratio. CONCLUSION: Mortality associated with CS continues to be an important
      public health problem that will resurge if adult syphilis rates increase. Because
      a large proportion of deaths occur at low gestational age, earlier diagnosis and
      treatment of maternal syphilis may substantially reduce the case fatality ratio.

PMID- 11986486
TI  - Influenza vaccination coverage level at a cystic fibrosis center.
AB  - BACKGROUND: Influenza causes substantial morbidity and mortality, particularly in
      vulnerable populations. Annual vaccination is the most effective means to prevent
      or attenuate this illness. The vaccine is recommended for patients with cystic
      fibrosis (CF) older than 6 months, but the degree of adherence with this
      recommendation is unknown. OBJECTIVES: To determine 1) the vaccination coverage
      level for the 1997-1998 influenza season in a population of CF patients, and 2)
      the factors associated with nonadherence with vaccination. DESIGN: Retrospective
      chart review, a mailed survey, and telephone interviews. SETTING: Intermountain
      CF Center. This center, accredited by the CF Foundation, delivers health care to
      affected individuals throughout the Intermountain West. Care of children and
      adults is based at Primary Children's Medical Center and the University of Utah
      Hospital, respectively. The adjacent hospitals are comprehensive, tertiary care
      medical centers on the University of Utah campus in Salt Lake City. Approximately
      one third of the center's patient population lives in southern Idaho. There are 2
      affiliate centers in Idaho, one based in Pocatello/Idaho Falls and the other in
      Boise. PATIENTS: All patients over 6 months of age on the center's roster.
      RESULTS: We found documentation of influenza vaccination status in the medical
      records of 99 patients; 98 who received the vaccine and 1 who did not because of
      an allergy to egg products. Through the mailed surveys and telephone interviews,
      we collected data on 236 additional patients. Thus, we report data on 335 (92.5%)
      of 362 patients on the center's roster. A total of 256 (76.4%) of 335 patients
      received the influenza vaccine before the 1997-1998 flu season, including 181
      (79.4%) of 228 children (<18 years of age) and 75 (70.1%) of 107 adult patients
      (</=18 years of age). We also analyzed the data assigning all patients to their
      major site of care, either the Salt Lake parent center or one of the Idaho
      affiliates. We found no difference in the vaccination rate when comparing parent
      center to affiliates: 179 (78.2%) of 229 patients at the parent center were
      vaccinated versus 77 (72.6%) of 106 patients at the affiliates. For the 79
      patients who did not obtain the influenza vaccine, the major reasons were:
      "forgot," "too healthy," "too busy," "worried about the side effects," or "too
      sick at the time." The unvaccinated group had fewer clinic visits, fewer CF
      related hospitalizations, and lived further from the care center than the
      vaccinated group. To further explore the association between contact with the
      center and vaccination status, we categorized patients into those who were
      evaluated in the outpatient clinic and/or hospitalized in 1997 and those who were
      not. We found that 80.8% of the 281 patients who actually received care at the
      center during 1997 were vaccinated as compared with only 59.5% of the 42 patients
      who did not receive care during that year. The timing of clinic visits also
      appears to be a critical factor. We found that 87.1% of patients who had a visit
      during the fourth quarter of the year had the vaccination as compared with 64.9%
      of patients who did not have a fourth quarter visit. A fourth quarter visit
      remained highly associated with vaccination in a logistic regression analysis,
      whereas number of clinic visits did not. CONCLUSIONS: The vaccination coverage
      level in this vulnerable population is higher than other high-risk groups of
      comparable age. Nonetheless, there is room for improvement. Strategies aimed at
      increasing patient contact with the CF center, particularly during the fourth
      quarter of the calendar year, may result in improved vaccination rates.
      Additional data encompassing a cross-section of CF centers would be helpful in
      ensuring that influenza vaccination is receiving adequate attention in this
      patient population. Systematic monitoring of influenza vaccination rates at a
      national level should be considered as a means of encouraging compliance with
      this important preventive measure. cystic fibrosis, influenza, vaccination,
      health care delivery.

PMID- 11986487
TI  - Economic burden of obesity in youths aged 6 to 17 years: 1979-1999.
AB  - OBJECTIVE: To examine the trend of obesity-associated diseases in youths and
      related economic costs. METHODS: Using a multiyear data file of the National
      Hospital Discharge Survey, 1979-1999, we analyzed the changes in obesity
      associated diseases and economic costs in youths (6-17 years of age) over time.
      Diabetes, obesity, sleep apnea, and gallbladder disease were examined to explore
      the trend of the disease burden. Other obesity-associated diseases for which
      obesity was listed as a secondary diagnosis were also analyzed. Obesity
      associated hospital costs were estimated from the discharges with obesity listed
      as a principal or secondary diagnosis. RESULTS: From 1979-1981 to 1997-1999, the
      percentage of discharges with obesity-associated diseases increased. The
      discharges of diabetes nearly doubled (from 1.43% to 2.36%), obesity and
      gallbladder diseases tripled (0.36% to 1.07% and 0.18% to 0.59%, respectively),
      and sleep apnea increased fivefold (0.14% to 0.75%). Ninety-six percent of
      discharges with a diagnosis of obesity listed obesity as a secondary diagnosis.
      Asthma and some mental disorders were the most common principal diagnoses when
      obesity was listed as a secondary diagnosis. Obesity-associated annual hospital
      costs (based on 2001 constant US dollar value) increased more than threefold;
      from $35 million (0.43% of total hospital costs) during 1979-1981 to $127 million
      (1.70% of total hospital costs) during 1997-1999. CONCLUSIONS: Among all hospital
      discharges, the proportion of discharges with obesity-associated diseases has
      increased dramatically in the past 20 years. This increase has led to a
      significant growth in economic costs. These findings may reflect the impact of
      increasing prevalence and severity of obesity. Diet and physical activity
      interventions should be developed for weight loss and prevention of weight gain
      in youths.

PMID- 11986488
TI  - Accuracy of pediatric primary care providers' screening and referral for early
      childhood caries.
AB  - PURPOSE: Tooth decay is one of the more common diseases of childhood. Slightly
      >40% of US children are already affected by the time they reach kindergarten.
      Primary care physicians can play an important role in prevention and control of
      this disease because of their ready access to this population. Unlike dentists,
      they see a large percentage of children during their infant and toddler years.
      However, few studies have been conducted on oral screenings and referrals by
      primary care physicians or the effectiveness of their oral health preventive
      activities. The purpose of this study was to determine the accuracy of pediatric
      primary care providers' screening and referral for Early Childhood Caries.
      METHODS: We sought to compare independent, blinded oral screening results and
      referral recommendations made by primary care providers with those of a pediatric
      dentist, considered for purposes of the study to be the reference gold standard.
      The study was conducted at a private pediatric group practice in North Carolina.
      The practice was selected because it serves a large volume of Medicaid patients
      and includes a large number of pediatric primary care providers (11 pediatricians
      and 1 nurse practitioner). Study participants included Medicaid-eligible children
      younger than 36 months of age with erupted teeth. The pediatric primary care
      providers in this practice received 2 hours of training in infant oral health.
      The training consisted of a review of the study methods and clinical slides
      illustrating dental caries in various stages of progression. Specific
      instructions were given to the providers on how to recognize a cavitated carious
      lesion and how to determine when a dental referral is needed. Providers were
      instructed to refer any child with 1 or more cavitated carious lesions, soft
      tissue pathology, or evidence of trauma to the teeth or mouth. Before commencing
      the study, calibration and a comparative analysis were performed to establish
      reliability and validity of the examinations performed by the pediatric dentist.
      Both a pediatric dentist and a pediatric primary care provider conducted a dental
      screening on each child and recorded carious teeth and whether a dental referral
      was needed. Sensitivity and specificity were calculated to compare the pediatric
      primary care providers' screenings to the gold standard (pediatric dentist) in 3
      categories: caries at the tooth level, caries at the patient level (1 or more
      affected teeth), and need for referral. RESULTS: The final study sample consisted
      of 258 preschool-aged children (122 males and 136 females) with a mean age of
      21.2 months (standard deviation [SD]: 9.13). One hundred eighty-four (71.3%) of
      the participants were white, 58 (22.5%) were black, and 16 (6.2%) were Hispanic.
      Tooth-Level Analysis: The pediatric dentist reported an average of 0.30 (SD:
      0.005) cavitated teeth per child, whereas the pediatric primary care providers
      reported a mean of 0.25 (SD: 0.004). This difference was not statistically
      significant (t test). The pediatric dentist identified 80 (2.4%) teeth with
      cavitated carious lesions, whereas the pediatric primary care providers
      identified 64 (1.9%), 25 of which were false-positives. Their screening results
      include 41 false-negative teeth. Thus, the primary care providers tended to under
      count the number of teeth with carious lesions. They achieved a sensitivity of
      0.49 (95% confidence interval [CI]: 0.47-0.51) and a specificity of 0.99 (95% CI:
      0.99-1.0) when their screening results for individual teeth were compared with
      the gold standard. Patient-Level Analysis: At the patient level, the pediatric
      dentist identified 25 (9.7%) children with 1 or more teeth affected by cavitated
      lesions. The pediatric primary care providers collectively identified 30 (11.6%)
      children who had cavitated lesions. They achieved a sensitivity of 0.76 (95% CI:
      0.71-0.81) and a specificity of 0.95 (95% CI: 0.93-0.98) in identifying those
      children with cavitated carious lesions. There were 6 false-negatives and 11
      false-positives when the pediatric primary care providers' findings were compared
      with the gold standard. At the patient-level, the positive predictive value of
      the dental screening was 0.63 and the negative predictive value was 0.97. Dental
      Referral: The pediatric dentist referred a total of 27 (10.5%) children to a
      dentist. Two of these children were referred for trauma and the other 25 were
      referred for cavities. The pediatric primary care providers referred a total of
      23 (8.9%) children to a dentist. Two referrals were made because the provider was
      concerned about stains on the teeth, whereas the remaining 21 were referred for
      cavities. The pediatric primary care providers achieved a sensitivity of 0.63
      (95% CI: 0.57-0.69) and a specificity of 0.98 (95% CI: 0.96-0.99) when their
      recommendations for referral were compared with the gold standard. The number of
      children receiving a referral from a pediatric primary care provider for cavities
      (N = 21) was less than the number of children they identified as having cavities
      (N = 30). The providers as a whole tended to under-refer, and only 70% of
      children with evidence of dental disease received a referral. CONCLUSIONS: After
      2 hours of training in infant oral health, the pediatric primary care providers
      in this study achieved an adequate level of accuracy in identifying children with
      cavitated carious lesions. Additional training and research would be needed to
      optimize pediatric primary care providers' identification of carious teeth if
      that were the goal of screening. However, the purpose of screening by nondental
      personnel generally is to accurately identify those in need of referral, which
      does not require a tooth-by-tooth identification of cavities. Additional research
      is also needed to determine how to improve dental referrals by pediatric primary
      care providers. Results of our study suggest that dental screenings can easily be
      incorporated into a busy pediatrics practice and that pediatric primary care
      providers can significantly contribute to the overall oral health of young
      children by the identification of those children who need to be seen by a
      dentist.

PMID- 11986489
TI  - Pediatrician counseling about preventive health topics: results from the
      Physicians' Practices Survey, 1998-1999.
AB  - OBJECTIVE: Government agencies and national organizations recommend that
      physicians counsel their child and adolescent patients about preventive health
      topics. Using data from a national survey, we describe the counseling patterns of
      pediatricians in regard to 9 recommended preventive health topics. METHODOLOGY:
      Between October 1998 and April 1999, information was collected from 907 of 1760
      primary care pediatricians randomly selected from a nationally representative
      sample. Through either a telephone interview or a mail survey, pediatricians were
      asked how frequently in the past month they counseled about 9 preventive health
      topics during the well-care visits or routine check-ups of their patients.
      Pediatricians answered questions regarding their patients aged 2 to 5, 6 to 12,
      and 13 to 18 years. RESULTS: Over 80% of the pediatricians counseled about 1 or
      more recommended preventive health topics during the well-care visits or routine
      check-ups of their patients. As compared with pediatricians who did not counsel
      about any topic, pediatricians who counseled were significantly more likely to be
      female and spend longer amounts of time with their patients during these visits.
      The frequency with which specific preventive health topics were discussed varied
      with the topic and the age of the patient. CONCLUSION: Most pediatricians
      routinely counsel about some, but not all, recommended preventive health topics.
      An understanding of why pediatricians selectively counsel about specific topics
      is needed.

PMID- 11986490
TI  - Black-white differences in health care utilization among US children with
      frequent ear infections.
AB  - OBJECTIVE: To examine differences in patterns of and barriers to health care
      utilization between black and white children who have frequent ear infections
      (FEI). METHODS: Analysis was conducted using the 1997 and 1998 National Health
      Interview Survey-Sample Child Files. Data on 25 497 children under 18 years of
      age and 1985 who were reported by the parent/guardian to have had "3 or more ear
      infections during the past 12 months" were analyzed. The data were weighted and
      analyzed to represent all black and white children nationwide, accounting for the
      complex survey design. RESULTS: Of white and black children under 18 years of age
      in the United States, 8.0 and 6.6%, respectively, had FEI in the past year. Among
      those with FEI, whites and blacks exhibited significantly different patterns in
      the type of health insurance they had and in the usual source of care. After
      accounting for sociodemographic factors, health insurance, and usual source of
      care, there were still significant differences in health care use between whites
      and blacks. The affected black children had an increased risk of getting delayed
      care because of transportation problems (odds ratio [OR]: 2.32) and a reduced
      likelihood of seeing a medical specialist (OR: 0.49) and having surgery (OR:
      0.39) in comparison to white children. CONCLUSION: Although black children with
      FEI were as likely as white children to be covered by health insurance and have a
      usual place of health care, they were significantly more likely to face barriers
      in obtaining the care, especially the more specialized care.

PMID- 11986491
TI  - Hearing screening.

PMID- 11986492
TI  - Cytomegalovirus infection.

PMID- 11986493
TI  - Screening for iron deficiency.

PMID- 11986494
TI  - Index of suspicion.

PMID- 11986495
TI  - Question from the clinician: fluoride supplementation and dental caries.

PMID- 11986496
TI  - The wheel, reinvented.

PMID- 11986498
TI  - Consumer & family information. How to help someone who is suicidal.

PMID- 11986499
TI  - State variations in complaint rates to protection and advocacy systems.

PMID- 11986500
TI  - Patients' preference for conventional antipsychotic medications.

PMID- 11986501
TI  - Training persons with schizophrenia in illness self-management: a randomized
      controlled trial in Japan.
AB  - Despite the worldwide shift from inpatient to community-based treatment for
      individuals with severe mental illness, Japanese psychiatric services remain
      hospital based. In 1998, Japan had 29 psychiatric beds per 10,000 persons, twice
      as many as in most European countries and five times as many as in the United
      States (1). The reasons for Japan's slow transition to a community-based mental
      health system are both economic and cultural. For instance, 90 percent of
      psychiatric beds are in private for-profit hospitals. There is little incentive
      for inpatient facilities to discharge patients promptly, because the Japanese
      health care system provides universal coverage with virtually unlimited
      reimbursement for inpatient services, and the government does not have a
      mechanism for financing the relocation of resources from hospitals to communities
      (2). In addition, the stigma associated with mental illness in Japanese families
      is high (3). Thus a patient's primary residence is the psychiatric hospital, and
      opportunities are provided for periodic visits from the family.However,
      psychiatric rehabilitation principles and practices are beginning to take root in
      Japan. Anzai and his colleagues at the Matsuzawa Psychiatric Hospital in Tokyo
      have adapted an empirically validated skills training program to prepare patients
      with schizophrenia for life in the community after discharge from the hospital.
      In this column, they report the results of a randomized controlled trial of this
      approach in an inpatient facility serving a large urban center.

PMID- 11986502
TI  - Detection of intimate-partner violence among members of a managed behavioral
      health organization.
AB  - This column describes a creative effort on the part of a national behavioral
      managed care plan to identify cases of domestic violence in its covered
      population. Although the screening efforts by intake counselors and clinicians
      yielded a lower rate of domestic violence than would have been expected, the
      effort established a baseline or benchmark from which the organization can now
      work. Clinical benchmarks are critical to developing an understanding of best
      practices. In this case, the benchmark finding initiated a best practices process
      through which this organization--and, hopefully, others--will continue to create
      better methods for identifying and helping people who experience domestic
      violence.

PMID- 11986503
TI  - When it really hurts to listen: psychotherapy in the aftermath of September 11.

PMID- 11986504
TI  - Role of social disadvantage in crime, joblessness, and homelessness among persons
      with serious mental illness.
AB  - Research on mental illness in relation to social problems such as crime,
      unemployment, and homelessness often ignores the broader social context in which
      mental illness is embedded. Policy, research, and practice will be improved if
      greater attention is given to social context. The authors critically analyze the
      approach used in much of the psychiatric services literature to infer links
      between mental illness and social problems. They compare these studies with
      studies that have been more validly conceptualized to account for social context.
      With this broader perspective, the impact of mental illness on crime,
      unemployment, and homelessness appears to be much smaller than that implied by
      much of the psychiatric services literature. Poverty moderates the relationship
      between serious mental illness and social problems. Factors related to poverty
      include lack of education, problems with employment, substance abuse, and a low
      likelihood of prosocial attachments. This relationship is often complicated and
      is not amenable to simple explanations. Research and policy that take this
      complexity into account may lead to greater effectiveness in interventions for
      persons with serious mental illness.

PMID- 11986506
TI  - Characteristics of suicide attempts in a large urban jail system with an
      established suicide prevention program.
AB  - OBJECTIVE: The King County Department of Adult and Juvenile Detention in
      Washington State, like many jail systems across the nation, implemented a suicide
      prevention program in response to high suicide rates. A review committee was
      formed to prospectively study the patterns of suicide attempts that occurred in
      the system after the program was implemented and to make recommendations for
      improvements. METHODS: All first suicide attempts per jail booking over a 33
      month period in two of the department's jails were studied. For each attempt,
      characteristics of the individual and of the attempt were abstracted by trained
      staff. RESULTS: A total of 132 first suicide attempts were made by 124 individual
      inmates during the study period. The prevalence of mental illness among inmates
      who attempted suicide was 77 percent, compared with 15 percent in the general
      jail population. Seventy-five percent of the inmates who attempted suicide had
      received a mental health evaluation from jail personnel before the attempt.
      Suicide attempts that were made in observation units for suicidal inmates (42
      percent of all attempts), particularly those made in group observation units,
      necessitated fewer visits to an emergency department than those that occurred in
      general areas of the jail. CONCLUSIONS: On the basis of these findings, the jails
      implemented interventions such as more suicide screening and treatment for
      inmates who have active substance abuse, greater consensus building in decisions
      about housing, and structural changes such as greater use of group-housing units
      and the use of barriers to prevent the inmates from jumping from balconies.

PMID- 11986507
TI  - Use of antidepressants to treat depression in bipolar disorder.
AB  - For decades, clinicians and researchers did not distinguish between bipolar and
      unipolar depression. The safety and efficacy of antidepressants for the treatment
      of unipolar depression were studied, and the data were applied to the treatment
      of bipolar depression without validation. As evidence has accumulated that
      antidepressants may adversely affect the course of bipolar illness, more research
      has been focused on that problem. Current evidence suggests that although
      antidepressants are clearly effective in the acute treatment of type I and type
      II bipolar depression, they are also associated with a variety of adverse
      outcomes. They may induce a switch to mania or hypomania at a rate two or three
      times the spontaneous rate. Long-term use may destabilize the illness, leading to
      an increase in the number of both manic and depressed episodes; induce rapid
      cycling (at least four episodes a year); and increase the likelihood of a mixed
      state. Antidepressants should be used with caution in the treatment of bipolar
      depression.

PMID- 11986508
TI  - Psychodynamic psychotherapy and clomipramine in the treatment of major
      depression.
AB  - OBJECTIVE: The authors compared a combination of clomipramine and psychodynamic
      psychotherapy with clomipramine alone in a randomized controlled trial among
      patients with major depression. METHODS: Seventy-four patients between the ages
      of 20 and 65 years who were assigned to ten weeks of acute outpatient treatment
      for major depression were studied. Bipolar disorder, psychotic symptoms, severe
      substance dependence, organic disorder, past intolerance to clomipramine, and
      mental retardation were exclusion criteria. RESULTS: Marked improvement was noted
      in both treatment groups. Combined treatment was associated with less treatment
      failure and better work adjustment at ten weeks and with better global
      functioning and lower hospitalization rates at discharge. A cost savings of 2,311
      dollars per patient in the combined treatment group, associated with lower rates
      of hospitalization and fewer lost work days, exceeded the expenditures related to
      providing psychotherapy. CONCLUSIONS: Provision of supplemental psychodynamic
      psychotherapy to patients with major depression who are receiving antidepressant
      medication is cost-effective.

PMID- 11986509
TI  - Exclusions and limitations in children's behavioral health care coverage.
AB  - OBJECTIVE: The objective of this study was to identify benefit limits, diagnostic
      exclusions, and service exclusions of private behavioral health care plans that
      can influence the delivery of care to children. METHODS: A total of 128
      commercial, employment-based behavioral health plans were examined for types of
      benefit limits, service exclusions, and diagnostic exclusions applicable to
      children. RESULTS: Almost half of the plans had restrictions on the number of
      outpatient visits, with limits ranging from 12 to 60 clinic visits a year. More
      than half of the plans had limitations on the number of inpatient days, ranging
      from 20 to 60 days a year. Diagnoses excluded from coverage included autism,
      mental retardation, problems related to child abuse, and impulse control
      disorders, such as kleptomania and pyromania. Half of the services excluded could
      be categorized as either social and human services or complementary medicine
      rather than as mental health care. CONCLUSIONS: Plans commonly had service and
      diagnostic exclusions that could disrupt children's health care. The results of
      the study emphasize a need to address the types of treatment covered by mental
      health insurance.

PMID- 11986510
TI  - Relationship of treatment orientation and continuing care to remission among
      substance abuse patients.
AB  - OBJECTIVES: The authors examined whether continuing outpatient mental health
      care, the orientation of the treatment program (12-step, cognitive-behavioral, or
      eclectic), and involvement in self-help groups were linked to substance abuse
      patients' remission status two years after discharge. METHODS: The data were from
      a cohort of 2,805 male patients who were treated through one of 15 Department of
      Veterans Affairs substance abuse programs. Remission was defined as abstinence
      from illicit drug use and abstinence from or nonproblem use of alcohol during the
      previous three months. The relationships of the three variables to remission were
      tested with regression models that controlled for baseline characteristics.
      RESULTS: About a quarter of the study participants (28 percent) were in remission
      two years after discharge. Intake characteristics that predicted remission at two
      years included less severe substance use and psychiatric problems, lower expected
      disadvantages and costs of discontinuing substance use, and having abstinence as
      a treatment goal. No significant relationship emerged between treatment
      orientation and remission status two years later. Involvement in outpatient
      mental health care during the first follow-up year and participation in self-help
      groups during the last three months of that year were associated with a greater
      likelihood of remission at the two-year follow-up. CONCLUSIONS: The results
      extend previously published one-year outcome findings showing that cognitive
      behavioral and 12-step treatment programs result in similar remission rates.
      Patients who enter intensive substance abuse treatment with polysubstance use,
      psychiatric symptoms, or significant emotional distress have more difficulty
      achieving remission. Routinely engaging patients in continuing outpatient care is
      likely to yield better outcomes. The duration of such care is probably more
      important than the number of sessions.

PMID- 11986511
TI  - The feasibility of enhancing psychiatric outpatients' readiness to change their
      substance use.
AB  - OBJECTIVE: This stage I therapy development study evaluated the feasibility and
      acceptability of a brief motivational intervention for outpatients with severe
      and persistent mental illness and drug use problems and examined preliminary
      indicators of outcome. METHODS: A motivational intervention was evaluated with 22
      outpatients. The intervention consisted of four individual sessions that were
      guided by the therapeutic principles of motivational interviewing. All
      participants met DSM-IV criteria for substance abuse or dependence within the
      previous six months and were not engaged in treatment for substance abuse.
      Substance use, treatment involvement, and attitudes toward substance use and
      cessation were assessed before and after the intervention and at a three-month
      follow-up session. RESULTS: The feasibility of the motivational intervention was
      demonstrated. The median time to completion of the intervention was 28 days. It
      was possible to retain psychiatric outpatients in the intervention, and the
      patients had favorable perceptions of the intervention. Readiness to change and
      involvement in treatment increased between preintervention and postintervention
      assessments. However, many of the postintervention gains had not been maintained
      at three-month follow-up. CONCLUSIONS: Use of brief motivational interventions
      can enhance patients' readiness to change substance use to better prepare them
      for drug treatment programs. Future interventions might benefit from the
      integration of the intervention with ongoing treatment to ensure that
      motivational gains are maintained.

PMID- 11986512
TI  - Palliative and aggressive end-of-life care for patients with dementia.
AB  - OBJECTIVES: The goals of this study were to establish the frequency of palliative
      and aggressive treatment measures among patients with and without dementia during
      the last six months of life, to identify relationships between the severity of
      dementia and aggressive and palliative care, and to determine whether treatment
      patterns have changed over time. METHODS: Antemortem data for 279 patients with
      dementia and 24 control patients who were brought for autopsy in chronic care
      facilities between 1985 and 2000 were reviewed. The severity of dementia was
      defined by scores on the Clinical Dementia Rating scale. Data on use of systemic
      antibiotics (designated as an aggressive treatment measure) and on use of
      narcotic and nonnarcotic pain medications and nasal oxygen (defined as palliative
      measures) were collected from medical charts. RESULTS: Fifty-three percent of the
      patients with dementia and 46 percent of those without dementia had received
      systemic antibiotics. Fourteen percent of the patients with dementia and 38
      percent of those without dementia had received narcotic pain medications. The
      prevalence of aggressive and palliative measures did not vary significantly with
      the severity of dementia. Eleven percent of the patients with dementia who died
      between 1991 and 1995 and 18 percent of those who died between 1996 and 2000 had
      received narcotic pain medications in the last six months of their lives.
      CONCLUSIONS: Use of systemic antibiotics is prevalent in the treatment of
      patients with end-stage dementia, despite the limited utility and discomfort
      associated with the use of these agents. That patients with severe dementia and
      those with milder cognitive impairment received similar treatment may be contrary
      to good clinical practice, given the poor prognosis of patients with severe
      dementia.

PMID- 11986513
TI  - Risk factors for psychosocial dysfunction among enrollees in the State Children's
      Health Insurance Program.
AB  - OBJECTIVE: The authors studied enrollees in the State Children's Health Insurance
      Program (SCHIP) (Title XXI) to characterize risk factors for psychosocial
      dysfunction among children of the working poor. METHODS: Medical and psychosocial
      variables were included in a survey completed by 393 parents of children enrolled
      in SCHIP. Regression analysis was used to examine the relationship between these
      variables and scores on the Pediatric Symptom Checklist, a measure of
      psychosocial dysfunction among children. RESULTS: Stepwise multiple regression
      showed that parental dysphoria, parental history of psychiatric or substance use
      problems, childhood chronic medical illness, and exposure to traumatic events
      each contributed independently to variance in psychosocial dysfunction in this
      population, explaining 34 percent of total variance. CONCLUSIONS: Despite strong
      progress in implementing SCHIP at the state level, the behavioral health care
      needs of children of the working poor have not been well defined. This study
      identified risk factors that can be easily found in the patient's medical record
      or detected during an interview by the primary care physician. Thus screening to
      identify children at risk of psychosocial dysfunction is warranted among SCHIP
      enrollees.

PMID- 11986514
TI  - Financial aspects of court-ordered evaluations.
AB  - The authors sought to establish the financial cost of involuntary court-ordered
      evaluations and potential strategies for reducing these costs. Medical charges
      from the time of admission to the time of the court hearing were calculated for
      998 patients who received involuntary court-ordered evaluations at the department
      of psychiatry of the Maricopa Medical Center in Phoenix, Arizona, in 1999. The
      average cost of an involuntary court-ordered evaluation was 8,236 dollars, and
      the average cost per day was 686 dollars. The analysis showed that several
      options could be used to reduce costs: expediting evaluations, holding court
      hearings on weekends and holidays, conducting evaluations on an outpatient basis,
      and housing patients in a less acute setting.

PMID- 11986515
TI  - Predictions made by psychiatrists and psychiatric nurses of violence by patients.
AB  - Studies have shown that it is difficult for psychiatrists to accurately predict
      which patients will be violent while hospitalized. The authors compared the
      predictions of 14 psychiatrists and nine psychiatric nurses who independently
      evaluated 308 patients consecutively admitted to a hospital in Israel and rated
      their likelihood of becoming violent. The psychiatrists and nurses also completed
      a general questionnaire about the criteria they used to predict violence. No
      significant differences were found in the accuracy of predictions between the two
      professional groups or in the criteria they used to predict violence. The total
      predictive value, or proportion of all cases predicted correctly, was 82 percent
      for the psychiatrists and 84 percent for the nurses. The predictions of the two
      groups coincided for 83 percent of the patients. The results suggest that
      psychiatrists and psychiatric nurses make similarly accurate predictions of
      violence and use similar criteria for making them.

PMID- 11986516
TI  - Return to treatment after assessment in a community children's mental health
      clinic.
AB  - Most people who receive mental health assessments do not follow up on needed
      treatment. The authors examined factors that predicted return for at least one
      treatment visit among 113 children who presented for treatment at a rural
      community mental health center, using predictors of return for adults from a
      previous study. Sixty-four percent of the children, compared with 46 percent of
      the adults, returned at least once. Time until the first appointment predicted
      whether patients returned for treatment. The age of the child was the only other
      variable that predicted initial treatment engagement. The results strongly
      suggest that community mental health agencies can improve treatment acceptance
      rates by providing rapid response to requests for treatment.

PMID- 11986517
TI  - The medicalization of the human condition.

PMID- 11986518
TI  - Stigma as a barrier to recovery.

PMID- 11986519
TI  - Is there a shortage of psychiatrists?

PMID- 11986520
TI  - Assertive community treatment in the UK.

PMID- 11986522
TI  - Clinical experience and prescribing practices.

PMID- 11986523
TI  - Evidence-based practices and recovery.

PMID- 11986526
TI  - Trauma and PTSD among substance-abusing patients.

PMID- 11986527
TI  - Surgical coronary revascularization in the elderly.

PMID- 11986528
TI  - Predictors of physical activity in older adults in an independent living
      retirement community.
AB  - This study was undertaken to examine potential predictors of physical activity in
      older adults in an independent living retirement community. Participants received
      a self-developed questionnaire that included questions regarding age, gender,
      educational attainment, physical activity habits, and physicians' physical
      activity counseling habits. One hundred nine of 150 questionnaires (72.7%) were
      completed and returned. Multivariate regression analyses revealed that younger
      age (p=0.013), higher educational attainment (p=0.003), positive attitude toward
      physical activity (p=0.030), and receiving advice from a physician to be
      physically active (p=0.001) were all positive predictors of increased physical
      activity. The results demonstrate that younger age, higher educational
      attainment, a positive attitude toward physical activity, and receiving advice
      from a physician to be physically active result in increased physical activity
      levels of older adults in an independent living retirement community.

PMID- 11986529
TI  - Long-term survival of quiescent left atrial myxoma in an elderly patient.
AB  - Left atrial myxoma, if left untreated, is inexorably progressive and usually
      fatal. The classical management of this disease is prompt surgical removal.
      However, there may be exceptions to this traditional dogma. The authors report an
      85-year-old man who presented with features of chronic obstructive airway disease
      and congestive heart failure 15 years previously. Auscultation of the heart
      showed a pansystolic murmur. Two-dimensional echocardiography revealed a
      nonobstructive, calcified, and well circumscribed mass in the left atrium, with a
      pedicle attached to the interatrial septum. Because the patient refused high-risk
      cardiac surgery related to his comorbidity, he was managed medically with a
      bronchodilator, diuretics, and digoxin. There have been no features of embolism
      or intracardiac obstruction, and serial echocardiography demonstrates no disease
      progression over this long period of time. This case illustrates that calcified
      left atrial myxoma may exhibit a quiescent phase. Tumor calcification, slow
      growth potential, and the absence of intracardiac obstruction may correlate with
      a better outcome in the elderly patient.

PMID- 11986530
TI  - Surgical coronary revascularization in geriatric patients.
AB  - Surgical coronary revascularization, especially in geriatric patients, is
      technically demanding and requires careful patient selection, selection of type
      of procedure, and postoperative care. Recent advances in coronary
      revascularization, especially in the variety of minimally invasive approaches and
      beating heart surgery, has enabled surgeons to operate upon elderly patients with
      improved results.

PMID- 11986531
TI  - Doppler echocardiographic assessment of left ventricular filling pressures in
      elderly patients with moderate/severe aortic stenosis.
AB  - Doppler-derived mitral inflow indices reflect left ventricular (LV) filling
      pressures but often vary with age. Diastolic filling is impaired in LV pressure
      overload states. The objective of this study was to determine the influence of
      age on the relationship between mitral inflow indices and LV filling pressures in
      patients with aortic stenosis. The authors studied 57 consecutive patients (age,
      77 years; 52% male) with moderate to severe aortic stenosis (aortic valve area <
      or =1.0 cm(2)) on cardiac catheterization and echocardiographic studies performed
      within 48 hours of catheterization. Patients with atrial fibrillation, aortic
      insufficiency, mitral stenosis, and paced rhythm were excluded. Echocardiographic
      variables obtained from five cardiac cycles were: E/A ratio and deceleration time
      (DT). Patients were subclassified by age (< and > or =75 years), ejection
      fraction ([EF] < and > or =50%), and coronary artery disease (CAD). Pulmonary
      capillary wedge pressure (PCWP) correlated with DT (r=-0.86; p=0.001) and with
      E/A (r=0.7; p=0.001) more strongly than did LV end-diastolic pressure. Age did
      not alter the relationship between DT and PCWP (r=-0.92; p=0.001 for < 75 years
      vs. r=-0.83; p=0.001 for > or =75 years). PCWP was predicted by the equation
      PCWP=-0.10DT+43, regardless of age. EF also had little influence on the
      correlation between PCWP and DT (r=-0.80; p=0.001 for EF < 50% vs. r=-0.94;
      p=0.001 for EF > or =50%). Similarly, there were no significant differences
      between the regression equations and correlations between the CAD and no-CAD
      groups: for CAD patients, PCWP=41.8-0.10DT; p < 0.0001; r=-0.84 (p < 0.0001). For
      no-CAD subjects, PCWP=46.2-0.12DT; p < 0.0001; r=20.92 (p < 0.0001). In patients
      with significant aortic stenosis, DT correlated strongly with PCWP but not with
      LV end-diastolic pressure. This relationship was independent of age, CAD, or EF.

PMID- 11986532
TI  - Primary diastolic heart failure.
AB  - Diastolic heart failure is defined clinically when signs and symptoms of heart
      failure are present in the presence of preserved left ventricular systolic
      function (ejection fraction >45%). The incidence and prevalence of primary
      diastolic heart failure increases with age and it may be as high as 50% in the
      elderly. Age, female gender, hypertension, coronary artery disease, diabetes, and
      increased body mass index are risk factors for diastolic heart failure.
      Hemodynamic consequences such as increased pulmonary venous pressure, post
      capillary pulmonary hypertension, and secondary right heart failure as well as
      decreased cardiac output are similar to those of systolic left ventricular
      failure, although the nature of primary left ventricular dysfunction is
      different. Diagnosis of primary diastolic heart failure depends on the presence
      of preserved left ventricular ejection fraction. Assessment of diastolic
      dysfunction is preferable but not mandatory. It is to be noted that increased
      levels of B-type natriuretic peptide does not distinguish between diastolic and
      systolic heart failure. Echocardiographic studies are recommended to exclude
      hypertrophic cardiomyopathy, infiltrative heart disease, primary valvular heart
      disease, and constrictive pericarditis. Myocardial stress imaging is frequently
      required to exclude ischemic heart disease. The prognosis of diastolic heart
      failure is variable; it is related to age, severity of heart failure, and
      associated comorbid diseases such as coronary artery disease. The prognosis of
      severe diastolic heart failure is similar to that of systolic heart failure.
      However, cautious use of diuretics and/or nitrates may cause hypotension and low
      output state. Heart rate control is essential to improving ventricular filling.
      Pharmacologic agents such as angiotensin receptor blockers, angiotensin
      converting enzyme inhibitors, and calcium channel blockers are used in selected
      patients to decrease left ventricular hypertrophy. To decrease myocardial
      fibrosis, aldosterone antagonists have a potential therapeutic role. However,
      prospective controlled studies will be required to establish their efficacy in
      primary diastolic heart failure.

PMID- 11986533
TI  - Ethical issues in the management of geriatric cardiac patients: a woman executed
      a living will with provisions that impeded its implementation.

PMID- 11986534
TI  - Electrocardiology teacher analysis and review: inferior peri-infarction block.

PMID- 11986535
TI  - Images in geriatric cardiology: transesophageal echocardiographic finding of
      bronchial artery dilatation in chronic obstructive pulmonary disease.

PMID- 11986536
TI  - Transfusion in the elderly with acute myocardial infarction.

PMID- 11986537
TI  - Noncardiac drugs and QTc interval prolongation: an often unrecognized risk factor
      for adverse cardiovascular outcomes.

PMID- 11986538
TI  - Staying on course: the effects of an adherence facilitation intervention on home
      exercise participation.
AB  - The purpose of this investigation was to test the effectiveness of an adherence
      facilitation intervention consisting of goal setting, graphic feedback, and
      provider guidance to support adherence to home exercise in a sample of patients
      with heart failure who had completed a supervised exercise program. The sample
      consisted of 13 patients with an ejection fraction of 40% or less who were
      randomly assigned to either the exercise only group (n=6) or the exercise with
      adherence facilitation group (n=7). The format of the intervention was graphic
      depiction of each patient's exercise goals in comparison to each patient's
      exercise participation. Graphs were mailed at 3-week intervals for 12 weeks.
      Results indicate that patients who received the intervention demonstrated higher
      exercise adherence and greater confidence in continuing to exercise in the
      future. The adherence facilitation intervention may be helpful to heart failure
      patients in adapting to a program of home exercise. (c)2002 CHF, Inc.

PMID- 11986539
TI  - Syncope: a fall from grace.
AB  - Falls by the elderly are not always what they appear to be on the surface. In the
      following paper, a woman must experience a long process of trial and error, as
      well as injury and suffering, before the underlying condition is finally
      uncovered by an astute nurse practitioner. The path to the diagnosis of syncope
      is a complex one, with economic, physical, and even social and psychological
      repercussions. Grace's "fall" not only contributes to burns and fractures, but
      damages her self-esteem and threatens her very independence. Armed with a
      thorough assessment, complete history, and the use of cardiac event recorders, a
      cardiovascular nurse has the unique opportunity to make a difference in the life
      of a patient suffering from suspicious falls and help her maintain a high quality
      of life.

PMID- 11986540
TI  - Healing the heart: integrating complementary therapies and healing practices into
      the care of cardiovascular patients.
AB  - Complementary therapies and healing practices have been found to reduce stress,
      anxiety, and lifestyle patterns known to contribute to cardiovascular disease.
      Promising therapies include imagery and hypnosis, meditation, yoga, tai chi,
      prayer, music, exercise, diet, and use of dietary supplements. Many of these
      complementary approaches to healing have been within the domain of nursing for
      centuries and can readily be integrated into the care of patients with
      cardiovascular disease. While individual complimentary modalities hold
      considerable merit, it is critical that the philosophy underlying these therapies
      -caring, holism, and harmony--also be understood and honored.

PMID- 11986541
TI  - The use of combination drug therapy in the treatment of hypertension.
AB  - Data from the National Health and Nutritional Examination Survey and from the
      World Health Organization have clearly demonstrated that, worldwide, less than
      one quarter of hypertensive patients are adequately controlled by our currently
      accepted blood pressure (BP) goals. These patients remain at significant risk for
      the development of cardiovascular disease. Although, there are multiple reasons
      contributing to inadequate blood pressure control, the most important include: 1)
      patient compliance; 2) acceptance of inadequate BP control by clinicians; 3)
      lower BP goals; and 4) the fact that it is very difficult or impossible to
      achieve adequate BP control with monotherapy in the majority of patients. The use
      of combination therapy, either as first-line treatment or much earlier in the
      course of treating hypertensive patients, may provide the solution to many of
      these management problems. Low-dose combination therapy provides several
      advantages in that: 1) it will be more effective than monotherapy due to the
      additive effect on BP of complementary drugs; 2) it will provide 24-hour efficacy
      with once-a-day dosing since most of the low-dose combination drugs include long
      acting components; 3) it will have a higher response rate than monotherapy and
      will be effective in most subgroups of hypertensive patients due to the
      complementary nature of combination therapy; 4) it may have fewer metabolic side
      effects than higher dose monotherapy since metabolic side effects also tend to be
      dose dependent; 5) it may have fewer dose-dependent side effects than
      monotherapy, as BP control is obtained at lower doses of each of the component
      drugs; 6) it is more convenient than monotherapy; 7) it may cost less, since low
      dose combination therapy tends to be a little more expensive than each of the
      components but cheaper than if each of the components were used separately. For
      these reasons, the use of low-dose combination therapy as first-line treatment or
      much earlier in the stepped-care approach may play a major role in improving the
      dismal control rates in hypertensive patients, which may ultimately have a
      positive impact on the rate of development of cardiovascular disease.

PMID- 11986542
TI  - The use of nesiritide in the management of acute decompensated heart failure.

PMID- 11986543
TI  - NHF-COACH multicenter trial in The Netherlands: searching for underlying
      potentially beneficial mechanisms in nurse led heart failure management.

PMID- 11986544
TI  - Heart transplantation for a prisoner.

PMID- 11986545
TI  - Why does the QRS morphology of the paced beat change in patients with
      biventricular cardiac pacing systems?

PMID- 11986546
TI  - The effects of simvastatin-niacin and antioxidant therapy on HDL.

PMID- 11986548
TI  - Electron beam computed tomographic scanning in preventive medicine.
AB  - Undetected coronary atherosclerosis is present in the majority of patients
      suffering myocardial infarction or sudden death. Electron beam computed
      tomography affords noninvasive scanning of the heart to detect and measure
      coronary calcification. These data permit dramatically improved assessment of
      both short-term and future risk for cardiac and other events. Knowledge of this
      risk gives the physician an opportunity for timely and cost-effective
      interventions.

PMID- 11986549
TI  - Beyond traditional risk factor analysis for coronary artery disease: the case for
      coronary artery calcium assessment with electron beam computed tomography.
AB  - Coronary artery disease is often asymptomatic, leading to inefficient detection.
      Although coronary artery disease is associated with multiple risk factors, better
      methods for detection are needed. The quantity of coronary artery calcium as
      detected with electron beam computed tomography is indicative of plaque mass, and
      the likelihood of coronary obstruction and future coronary events is independent
      of other risk factors. Screening for coronary artery disease with electron beam
      computed tomography offers a complimentary way of detecting early atherosclerosis
      in asymptomatic patients.

PMID- 11986550
TI  - A treatise on the "mammogram of the heart".
AB  - The enormous toll that coronary heart disease takes on our population merits
      serious consideration of all possible approaches toward early detection and
      prevention. It is pedestrian to the knowledgeable epidemiologist to state that
      coronary disease will kill more than twice as many women this year than will
      breast cancer. Coronary disease kills men at an even greater rate. If we had an
      effective preventive strategy involving early screening for one disease, why not
      find and apply a similar strategy for the other? Its vocal proponents have touted
      the coronary computed tomographic scan for calcification as the mammogram of the
      heart. However, unlike the breast mammogram, there are no studies showing that
      those tested fare any better than those who forego testing, in other words, that
      the test actually improves prognosis. Furthermore, the results regarding the
      prognostic value of computed tomographic screening are far from completely
      conclusive and will not be until the ongoing Multi-Ethnic Study of
      Atherosclerosis (MESA) trial (available at: http://140.142.220.3/mesa/) is
      completed.

PMID- 11986551
TI  - A review of electron beam computed tomography: implications for coronary artery
      disease screening.
AB  - Coronary artery disease is the leading cause of death in the United States, thus
      the intense interest in a screening test that would allow early identification of
      coronary artery disease in its asymptomatic stage, allowing early aggressive
      targeted risk factor reduction. While office-based risk factor assessment is
      currently the reference standard for prediction of cardiac risk, several imaging
      tests are currently being investigated. Electron beam computed tomography (EBCT)
      can accurately identify calcium in the coronary tree noninvasively. Coronary
      calcium is clearly linked with coronary atherosclerosis. In population studies,
      populations with higher calcium scores have more calcium events. The predictive
      value of a calcium score for an individual is currently under investigation, as
      well as the incremental value of a calcium score over office-based risk
      assessment in cardiac risk prediction. This review looks at the current role of
      EBCT in the prevention of cardiovascular disease. It summarizes the current data
      for calcium as a screening tool, which is strongest in establishing that
      asymptomatic people undergo increased rates of revascularization after an EBCT
      test. Widespread clinical use of EBCT is not recommended, pending data to
      establish its efficacy in the role of risk factor reduction and prevention of
      cardiovascular disease.

PMID- 11986552
TI  - Three-dimensional coronary anatomy in contrast-enhanced multislice computed
      tomography.
AB  - A number of three-dimensional imaging modalities, such as magnetic resonance
      imaging, electron beam computed tomography, ultrasonography, and multislice
      computed tomography have been introduced in cardiovascular medicine. One of the
      most recently developed techniques, multislice computed tomographic coronary
      angiography, allows assessment of the small coronary vessels. The entire heart is
      scanned within a single breathhold and contrast-enhanced images are reconstructed
      through retrospective electrocardiographic gating. Instead of the conventional
      two-dimensional projection images, multislice computed tomographic data can be
      displayed in a three-dimensional, volume-rendered manner. This paper presents an
      overview of the cardiac and coronary morphology as it is imaged with contrast
      enhanced multislice computed tomography. Further imaging characteristics of
      computed tomographic angiography are discussed.

PMID- 11986553
TI  - Will helical CT replace electron beam CT in the assessment of coronary calcium?
AB  - Accurate determination of coronary calcification has, until recently, required
      the use of electron beam computed tomography to acquire images with sufficient
      time and spatial resolution. Recent technologic advances in helical computed
      tomography, including rapid gantry rotation, multidetector arrays, and the use of
      electrocardiographic gating have resulted in image acquisition which parallels
      that of electron beam computed tomography. Direct comparisons of these techniques
      have shown relative equivalence in calcium scores, and the availability of
      helical computed tomography suggests that this technique will result in the
      proliferation of coronary computed tomographic scanning.

PMID- 11986554
TI  - Perspectives: some thoughts on the Adult Treatment Panel III report.
AB  - The guidelines of the Adult Treatment Panel III (ATP III) of the National
      Cholesterol Education Program are similar to prior recommendations in focusing on
      elevations of low-density lipoprotein (LDL) cholesterol as the primary target of
      therapy and in gauging the intensity of therapy to the degree of coronary heart
      disease risk. New elements in the current guidelines include: quantification of
      risk, heightened attention to the risk imparted by low high-density lipoprotein
      levels, utilization of non-high-density lipoprotein cholesterol levels in risk
      assessment for hypertriglyceridemic individuals, and emphasis on the metabolic
      syndrome. Nonetheless, the current guidelines are not perfect. The recommended
      algorithm for treatment is excessively complex; this complexity may keep the
      guidelines from being widely used. This complexity is generated by a hybrid
      scheme of risk assessment utilizing both counting of categorical coronary heart
      disease risk factors and calculation of coronary heart disease using the
      Framingham model. This hybrid method also results in undesirable inconsistencies
      in treatment. ATP III explicitly agrees that the therapeutic LDL goal should be
      determined by the burden of non-LDL risk factors. However, the current guidelines
      violate this principle by giving the baseline LDL cholesterol level a role in
      determining the therapeutic LDL goal. Additionally, the ATP III guidelines lead
      to under-treatment of women. Simplification should be a goal of the next
      iteration of the guidelines. Specific suggestions are given for simplification of
      the guidelines and for enhanced treatment of women. Furthermore, it is urged that
      the risk-assessing spreadsheet be provided in an "unlocked" form so that its
      details can be inspected.

PMID- 11986555
TI  - Problems with the new Adult Treatment Panel III guidelines.

PMID- 11986556
TI  - Did you know? Chelation therapy: new proof of lack of efficacy.

PMID- 11986557
TI  - Pursuit of the ideal perfusion agent.

PMID- 11986559
TI  - Validation of SPECT equilibrium radionuclide angiographic right ventricular
      parameters by cardiac magnetic resonance imaging.
AB  - BACKGROUND: Recent advances in the treatment of primary pulmonary hypertension
      (PPH), and in surgery to correct tetralogy of Fallot (TOF), have rekindled
      interest in evaluating right ventricular (RV) volume and ejection fraction (EF).
      The purpose of this investigation was to determine the accuracy of RV functional
      parameters assessed by single photon emission computed tomography (SPECT)
      equilibrium radionuclide angiography (ERNA). METHODS AND RESULTS: Twenty-eight
      patients with PPH (n = 15) or TOF (n = 13) (aged 28 +/- 14 years; 57% male) were
      analyzed by means of SPECT ERNA algorithms that automatically identified mid-RV
      tomographic planes, generated regions isolating the right ventricle from other
      structures, and presented RV-segmented regions as a cinematic display. RV EF and
      volumes were computed and compared with values obtained by magnetic resonance
      imaging (MRI). Mean values were not different between SPECT ERNA and MRI for RV
      EF, end-diastolic volume, and end-systolic volume (42% +/- 11% vs 41% +/- 10%,
      135 +/- 67 mL vs 139 +/- 91 mL, and 87 +/- 54 mL vs 85 +/- 61 mL, respectively; P
      = not significant for all comparisons). Significant linear correlation (P <.0001)
      was found between SPECT ERNA and MRI for RV EF, end-diastolic volume, and end
      systolic volume (r = 0.85, r = 0.94, and r = 0.93, respectively). No
      statistically significant trends or biases for RV EF were found. Intraobserver
      and interobserver comparisons demonstrated good reproducibility. As expected, RV
      volume was significantly higher and RV EF was significantly lower for patients
      with PPH and TOF than were values for individuals at low likelihood for coronary
      artery disease or other cardiac disease. CONCLUSIONS: SPECT ERNA provides
      accurate, reproducible assessment of RV volumes and EF and should prove useful in
      evaluating the magnitude of RV dysfunction in patients and in providing an
      objective means with which to assess the results of therapeutic interventions.

PMID- 11986560
TI  - Identification of extensive coronary artery disease: incremental value of
      exercise Tl-201 SPECT to clinical and stress test variables.
AB  - BACKGROUND: The ability of the size of a total myocardial perfusion defect (MPD)
      to detect extensive coronary artery disease (CAD) is currently suboptimal with
      exercise thallium 201 single photon emission computed tomography (SPECT). To
      improve its performance, exercise electrocardiography and indirect scintigraphic
      markers of extensive CAD were proposed (increased right ventricular Tl-201
      uptake, lung-to-heart [L/H] ratio, and left ventricular transient ischemic
      dilation ratio). We aimed to determine the additive value of these criteria for
      the detection of extensive CAD. METHODS AND RESULTS: The population included 338
      patients who underwent exercise Tl-201 SPECT and coronary angiography. Patients
      were classified as having extensive CAD (left main, multivessel, or 1-vessel
      proximal left anterior descending CAD) or limited CAD (1-vessel disease other
      than proximal left anterior descending CAD or no CAD). First, Tl-201 SPECT
      provided higher diagnostic value than exercise electrocardiography. Second, age,
      percent target heart rate achieved, total MPD, and L/H ratio were independent
      predictors of extensive CAD. Third, visually estimated abnormal right ventricular
      Tl-201 uptake did not present additional information. Fourth, L/H ratio presented
      a higher diagnostic accuracy than left ventricular transient ischemic dilation
      ratio. CONCLUSIONS: With exercise Tl-201 SPECT, age, percent target heart rate
      achieved, total MPD, and L/H ratio were independent predictors of extensive CAD.

PMID- 11986561
TI  - Value of exercise data for the interpretation of myocardial perfusion SPECT.
AB  - BACKGROUND: Artificial neural networks have successfully been applied for
      automated interpretation of myocardial perfusion images. So far the networks have
      used data from the myocardial perfusion images only. The purpose of this study
      was to investigate whether the automated interpretation of myocardial perfusion
      images with the use of artificial neural networks was improved if clinical data
      were assessed in addition to the perfusion images. METHODS AND RESULTS: A
      population of 229 patients who had undergone both rest-stress myocardial
      perfusion scintigraphy in conjunction with an exercise test and coronary
      angiography, with no more than 3 months elapsing between the 2 examinations, were
      studied. The networks were trained to detect coronary artery disease or
      myocardial ischemia with the use of 2 different gold standards. The first was
      based on coronary angiography, and the second was based on all data available
      (including perfusion scintigrams, coronary angiography, exercise test, resting
      electrocardiography, patient history, etc). The performance of the neural
      networks was quantified as areas under the receiver operating characteristic
      curves. The results showed that the neural networks trained with perfusion images
      performed better than those trained with exercise data (0.78 vs 0.55, P <.0001),
      with coronary angiography used as the gold standard. Furthermore, the networks
      did not improve when data from the exercise test were used as input in addition
      to the perfusion images (0.78 vs 0.77, P =.6). CONCLUSIONS: The results show that
      the clinically important information in combined exercise test and myocardial
      scintigraphy could be found in the perfusion images. Exercise test information
      did not improve upon the accuracy of automated neural network interpretation of
      myocardial perfusion images in a receiver operator characteristic analysis of
      test accuracy.

PMID- 11986562
TI  - Prediction of long-term effects of revascularization on regional and global left
      ventricular function by dobutamine echocardiography and rest Tl-201 imaging alone
      and in combination in patients with chronic coronary artery disease.
AB  - BACKGROUND: The aim of this study was to evaluate the accuracy of low-dose
      dobutamine echocardiography (DE) and resting thallium 201 single photon emission
      computed tomography (SPECT) alone and in combination for prediction of functional
      recovery at late follow-up (1 year) after revascularization. METHODS AND RESULTS:
      Twenty-six patients with coronary artery disease and ventricular dysfunction
      (ejection fraction, 42% +/- 9%) underwent DE and Tl-201 SPECT 14 +/- 9 (mean +/-
      SD) days before revascularization and repeated echocardiography 12 +/- 5 months
      thereafter. Discriminant analysis was applied to combine Tl-201 SPECT and DE data
      to classify dysfunctional segments as viable or nonviable. In 78
      akinetic/dyskinetic revascularized segments, Tl-201 SPECT provided a sensitivity
      of 83% and a specificity of 55%, whereas DE showed a sensitivity of 60% and a
      specificity of 91%, for prediction of improvement in regional function at follow
      up. The combination of data through use of discriminant analysis provided a
      sensitivity of 80% and a specificity of 86%, with an overall accuracy of 82%,
      significantly higher than DE (71%; P <.05) and Tl-201 SPECT (73%; P <.05) alone.
      Moreover, discriminant analysis identified 12 (75%) of 16 patients with and 8
      (80%) of 10 patients without significant improvement in ejection fraction at
      follow-up, with an accuracy of 77%. CONCLUSIONS: The combination of Tl-201 SPECT
      and DE data provides higher accuracy than either technique alone for prediction
      of recovery of regional and global function after revascularization.

PMID- 11986563
TI  - Attenuation correction and gating synergistically improve the diagnostic accuracy
      of myocardial perfusion SPECT.
AB  - BACKGROUND: The diagnostic accuracy of myocardial perfusion single photon
      emission computed tomography is limited by soft tissue attenuation. Artifacts may
      be reduced by attenuation correction (AC) or compensated for by assessment of
      wall motion in gated images. We studied the benefit of gating and AC, both
      separately and combined, in improving accuracy. METHODS AND RESULTS: Sixty-six
      subjects (27 with > or =50% angiographic stenosis, 5 with <50% stenosis, and 34
      Bayesian normal volunteers) underwent gated AC single photon emission computed
      tomography. Images were reconstructed and independently viewed in 4 ways: static
      with motion correction (MC) only, gated with MC only, static with MC plus blur
      correction plus AC (referred to as combined corrections [CC]), and gated with CC.
      Images were interpreted by 2 blinded observers for overall presence of coronary
      disease and for vascular territory (left anterior descending [LAD], left
      circumflex [LCx], and right coronary artery [RCA]). Statistical analysis of
      sensitivity and normalcy was done by means of the Cochran Q test. Overall
      diagnostic accuracy showed statistically significant improvement (P =.05 for
      sensitivity, P <.001 for normalcy), progressing from static MC to gated MC to
      static CC to gated CC (sensitivity/normalcy = 85%/54%, 78%/62%, 93%/77%, and
      96%/85%, respectively, for the 4 reconstruction and viewing approaches).
      Sensitivity was highest in all 3 vascular territories for the combination of
      gating and CC; normalcy was also highest with the same combination for the LAD
      and RCA territories; sensitivity/normalcy with this combination was 85%/87% for
      the LAD, 69%/87% for the LCx, and 89%/87% for the RCA territory. CONCLUSIONS: The
      combination of gating and CC provides the highest diagnostic accuracy, and gating
      and AC should thus be considered complementary and synergistic.

PMID- 11986564
TI  - Pharmacologic stress perfusion imaging with adenosine: role of simultaneous low
      level treadmill exercise.
AB  - BACKGROUND: Adenosine is commonly used for pharmacologic stress myocardial
      perfusion imaging (MPI). However, it frequently results in adverse effects, and
      the subdiaphragmatic tracer uptake may interfere with the image interpretation.
      Our aim was to determine the feasibility of combining low-level treadmill
      exercise with adenosine MPI and its impact on adverse effects, image quality, and
      myocardial ischemia. METHODS AND RESULTS: Forty-one patients underwent technetium
      99m sestamibi single photon emission computed tomography following adenosine and
      adenosine with low-level exercise (adenosine-Ex) on separate occasions and rest
      MPI. A comparison was made of symptoms, hemodynamic response,
      electrocardiographic changes, image quality, and image interpretation between the
      2 protocols. With adenosine-Ex, fewer patients had one or more adverse effects
      (61% vs 90%; P =.006), more patients had ischemic electrocardiographic changes
      (34% vs 15%; P =.03), a higher percentage had excellent- or fair-quality images
      (88% vs 61%; P =.003), and they had higher heart-liver ratios (1.0 +/- 0.37 vs
      0.84 +/- 0.29; P =.002) compared with adenosine alone. Four adenosine MPI
      studies, but only 2 adenosine-Ex studies, were uninterpretable because of
      excessive subdiaphragmatic radiotracer activity. Of the 39 patients with at least
      1 interpretable stress study, interpretation was discordant in 11 (28%): 7 showed
      greater ischemia with adenosine-Ex, 2 uninterpretable adenosine studies were
      interpretable with adenosine-Ex, and 2 studies interpreted as abnormal with
      adenosine were normal by adenosine-Ex (both had normal coronary angiograms).
      CONCLUSIONS: Simultaneous low-level treadmill exercise with adenosine Tc-99m
      sestamibi imaging is safe and feasible, significantly reduces unfavorable side
      effects, enhances image quality, and may result in greater ischemia detection
      compared with adenosine alone.

PMID- 11986565
TI  - Removal of liver activity contamination in teboroxime dynamic cardiac SPECT
      imaging with the use of factor analysis.
AB  - BACKGROUND: One of the major problems associated with technetium 99m teboroxime
      cardiac imaging is the high concentration of activity in the liver. In some cases
      it is impossible to diagnose defects on the inferior wall because of the finite
      resolution and scatter that cause images of the inferior wall and the liver to
      overlap. METHODS AND RESULTS: The least-squares factor analysis of dynamic
      structures method, with correction for non-unique solutions, was used to remove
      the liver activity from the image. The method was applied to dynamically acquired
      Tc-99m teboroxime data. The liver activity removal method was tested through use
      of computer simulations and tomographically acquired canine and patient cardiac
      studies. In all studies the least-squares factor analysis of dynamic structures
      method was able to extract the liver activity from the series of dynamic images,
      thereby making it possible to remove it quantitatively from the entire series.
      The method was used successfully to remove the liver activity that partially
      overlapped the inferior wall in normal hearts. The method tends to increase the
      contrast between defects and normal myocardial tissue in abnormal hearts.
      CONCLUSIONS: The method presented can be used to assist in diagnosis of cardiac
      disease when dynamically acquired teboroxime data are used. Because the contrast
      between the defect and normal myocardial tissue can be changed, the processed
      image cannot be used by itself to make an accurate diagnosis. However, with the
      liver activity removed, the image provides additional information that is very
      useful in the imaging of patients whose liver activity overlaps the inferior
      heart wall.

PMID- 11986566
TI  - The molecular basis of cardiac arrhythmias.

PMID- 11986568
TI  - The right stuff.

PMID- 11986569
TI  - Assessment of myocardial viability after myocardial infarction.

PMID- 11986567
TI  - Peripheral limitations of maximal aerobic capacity in patients with chronic heart
      failure.

PMID- 11986570
TI  - Significance of right ventricular visualization on stress sestamibi in a patient
      with dyspnea after atrial septal defect repair.

PMID- 11986571
TI  - Correlation of coronary artery anatomy with myocardial perfusion maps.

PMID- 11986572
TI  - Standardized myocardial segmentation and nomenclature for tomographic imaging of
      the heart. A statement for healthcare professionals from the Cardiac Imaging
      Committee of the Council on Clinical Cardiology of the American Heart
      Association.

PMID- 11986573
TI  - American Society of Nuclear Cardiology position statement on radionuclide imaging
      in patients with suspected acute ischemic syndromes in the emergency department
      or chest pain center.

PMID- 11986574
TI  - The Bournemouth Questionnaire: a short-form comprehensive outcome measure. II.
      Psychometric properties in neck pain patients.
AB  - OBJECTIVE: To modify an existing outcome measure (Bournemouth Questionnaire [BQ])
      for use in patients with nonspecific neck pain and test its psychometric
      properties. DESIGN: Prospective longitudinal study in which the questionnaire was
      administered on 3 occasions (pretreatment, retest, and posttreatment). SETTING:
      Anglo-European College of Chiropractic outpatient clinic and 8 field chiropractic
      practices. METHOD: Seven core items relating to the biopsychosocial model of pain
      were included in the original questionnaire (back BQ). The wording of one of
      these items (disability in activities of daily living) was modified to include
      activities likely to be affected by neck pain. Testing of the neck BQ was carried
      out in 102 patients with nonspecific neck pain. RESULTS: The instrument
      demonstrated high internal consistency on 3 administrations (Cronbach's alpha =
      0.87, 0.91, 0.92). All 7 items were retained on the basis that they each
      significantly contributed to the total score (item-corrected total score
      correlations >0.43) and to the instrument's responsiveness to clinical change
      (item change-corrected total change score correlations >0.42). The instrument was
      reliable in test-retest administrations in stable subjects (ICC = 0.65). The
      instrument demonstrated acceptable construct validity and longitudinal construct
      validity with established external measures. The treatment effect size of the
      instrument was found to be high (1.67). CONCLUSION: The neck BQ covers the
      salient dimensions of the biopsychosocial model of pain, is quick and easy to
      complete, and has been shown to be reliable, valid, and responsive to clinically
      significant change in patients with nonspecific neck pain. Its use as an outcome
      measure in clinical trials and outcomes research is recommended.

PMID- 11986575
TI  - The effect of chiropractic manipulation on salivary cortisol levels.
AB  - BACKGROUND: The stress response in humans is a healthy response and is necessary
      for life. The effects of chiropractic manipulation (CM), if any, on stress are
      ill-defined. Cortisol has been used as an accurate measure of the stress response
      system in humans. Salivary cortisol is a noninvasive technique to accurately
      quantify biologically active cortisol. OBJECTIVE: To determine whether basal
      salivary cortisol levels can be properly detected and whether CM has any direct
      effect on basal salivary cortisol levels in humans. METHODS: Subjects were adult
      male students attending a chiropractic college. Salivary samples were collected
      for 5 weeks. During Week 1, samples were collected by the students at home upon
      waking. During Weeks 2 through 5, home samples were collected upon waking and
      were followed by an additional time course of samples collected in a laboratory
      setting before and after CM. Salivary cortisol was measured by enzyme-linked
      immunoassay. RESULTS: Chiropractic manipulative therapy did not significantly
      change basal salivary cortisol levels. The time course of acute changes to
      cortisol levels was independent of testing week and group. A decrease in salivary
      cortisol was detected over time on each trial testing day. Overall, cortisol
      levels significantly decreased from the time of the home samples until the
      pretreatment laboratory measurement (P <.05). Cortisol levels subsequently
      decreased from pretreatment to 15 minutes after treatment (P <.05). After
      treatment, there were progressive decreases in cortisol levels from the 15- and
      30-minute time points to the 60-minute time point (P <.05). CONCLUSION: The
      results of this pilot study suggest that there is no effect of CM on salivary
      cortisol levels in asymptomatic subjects. As such, we conclude that neither the
      anticipation of CM nor the spinal manipulative procedure itself induces a state
      of stress or anxiety.

PMID- 11986576
TI  - A comparison of methods of evaluating cervical range of motion.
AB  - OBJECTIVE: To determine whether there are differences in results when evaluating
      cervical range of motion (ROM) with radiographic analysis, a bubble goniometer,
      and a dual inclinometer and whether particular physical parameters are related to
      cervical ROM. METHODS: We evaluated the cervical ROM of 115 volunteers with each
      of the 3 clinical methods. Tape measurements of neck girth, distance from chin to
      sternal notch, and distances from ears to acromion were also recorded, along with
      sex and age. Interrater and intrarater reliabilities were determined, and the
      Pearson product moment correlation test and t test were performed on all data.
      RESULTS: Cervical ROM as determined by radiographic analysis was greater than
      that obtained with either a dual inclinometer or a bubble goniometer. All tape
      measurements were weakly correlated with all 3 means of cervical ROM evaluation,
      with the exception of the measurement of ear lobes to acromion, which did not
      correlate with radiographic analysis. There were also differences found in
      cervical ROM by sex and by age, with female subjects and younger subjects having
      a greater ROM. CONCLUSION: Compared with a dual inclinometer and a bubble
      goniometer, radiographic analysis provides a more accurate evaluation of cervical
      ROM.

PMID- 11986577
TI  - Chiropractic patients in Denmark: a short description of basic characteristics.
AB  - BACKGROUND: The vast majority of information on chiropractic and chiropractic
      patients originates from English-speaking countries. Lately, however, reports
      describing chiropractic patients and practice in other European countries have
      emerged. OBJECTIVE: To describe basic characteristics of Danish chiropractic
      patients. DESIGN: Survey questionnaire. All chiropractic clinics in Denmark were
      asked to collect information on new patients during 1 randomly assigned week in
      1999. SETTING: Private chiropractic practice and a nonprofit research
      institution. OUTCOME MEASURES: Age and sex, location and duration of chief
      complaint, pain intensity, limitation of activities of daily living from chief
      complaint, and mode of referral. RESULTS: Eighty-eight percent of all
      chiropractic clinics in Denmark participated in the study. Out of 2020 patients
      from the participating clinics, 1897 (94%) filled out a self-administered
      questionnaire. The mean age of participants was 42 years, and slightly more women
      than men returned the questionnaire. By far the most frequent area of complaint
      was pain related to the lower back (50%) followed by pain related to the neck
      (15%). The majority of patients had complaints in the subacute or chronic
      category (duration 1-6 months). Patients with sciatica had significantly higher
      pain scores and limitation in activities of daily living (ADL) than any other
      group, whereas patients with neck pain tended to score lower. Patients in the
      subacute category had the highest pain scores and limitation in ADL. For
      complaints lasting more than 6 months, limitation in ADL remained constant at a
      low level. Twenty-three percent of all patients were referred to the
      chiropractor, most frequently by a general medical practitioner. More than half
      of all patients had previously been treated for the same or similar problems,
      most frequently by a chiropractor. Fifty-one percent had also received
      chiropractic care for other types of problems. CONCLUSIONS: Most Danish
      chiropractic patients complain of pain related to the low back or neck of between
      1 and 6 months' duration. This study confirms that chiropractic is fairly well
      integrated in the Danish primary health care system. There are differences
      between the chiropractic patient population in Denmark compared with that of
      Sweden and Holland.

PMID- 11986578
TI  - The diet-induced proinflammatory state: a cause of chronic pain and other
      degenerative diseases?
AB  - BACKGROUND: It is the rare physician who includes diet therapy and nutritional
      supplements in patient care. Perhaps this is because chiropractic and medical
      schools devote very few classroom hours to nutrition. It is also possible that
      physicians are under the misconception that a detailed biochemical understanding
      of each individual disease is required before nutritional interventions can be
      used. OBJECTIVE: The purpose of this article is two-fold: (1) to demonstrate that
      chronic pain and other degenerative conditions encountered in clinical practice
      have similar biochemical etiologies, such as a diet-induced proinflammatory
      state, and (2) to outline a basic nutritional program that can be used by all
      practitioners. DATA SOURCES: The data were accumulated over a period of years by
      reviewing contemporary articles and books and subsequently by retrieving relevant
      articles. Articles were also selected through MEDLINE and manual library
      searches. RESULTS: The typical American diet is deficient in fruits and
      vegetables and contains excessive amounts of meat, refined grain products, and
      dessert foods. Such a diet can have numerous adverse biochemical effects, all of
      which create a proinflammatory state and predispose the body to degenerative
      diseases. It appears that an inadequate intake of fruits and vegetables can
      result in a suboptimal intake of antioxidants and phytochemicals and an
      imbalanced intake of essential fatty acids. Through different mechanisms, each
      nutritional alteration can promote inflammation and disease. CONCLUSION: We can
      no longer view different diseases as distinct biochemical entities. Nearly all
      degenerative diseases have the same underlying biochemical etiology, that is, a
      diet-induced proinflammatory state. Although specific diseases may require
      specific treatments, such as adjustments for hypomobile joints, beta-blockers for
      hypertension, and chemotherapy for cancer, the treatment program must also
      include nutritional protocols to reduce the proinflammatory state.

PMID- 11986579
TI  - Transcranial sonography and vertebrobasilar insufficiency.
AB  - OBJECTIVE: The objective was to discuss a case illustrating the role of
      transcranial Doppler sonography in the screening and treatment of a patient with
      intermittent vertebral artery brainstem ischemia. CLINICAL FEATURES: A 28-year
      old woman had neck pain, arm pain, headaches, and dizziness. Her symptoms
      occurred intermittently over several years. Past care had provided little relief.
      De Kleyn's test, transcranial Doppler sonography, and magnetic resonance
      imaging/magnetic resonance angiography helped establish a diagnosis of
      vertebrobasilar syndrome. INTERVENTION AND OUTCOME: The patient was referred for
      neurosurgical evaluation. She subsequently chose to be treated with spinal
      manipulative therapy. Her neck pain, headaches, and radicular symptoms resolved.
      The dizzy spells abated to a tolerable level. The neurosurgeon subsequently re
      evaluated the patient and recommended that surgery not be performed. CONCLUSIONS:
      This illustrates a case of extra-arterial mechanical compression of the vertebral
      arteries documented by transcranial Doppler sonography procedures. Brainstem
      symptoms were correlated with a documented perfusion deficit during cervical
      positional testing. This case also demonstrated that spinal manipulative therapy
      may be safely used on patients with vertebrobasilar insufficiency when the
      biomechanics and related flow studies are elucidated.

PMID- 11986580
TI  - Ganglioneuroma masquerading as spinal pain.
AB  - OBJECTIVE: To discuss the clinical features of ganglioneuroma and to propose it
      as a differential diagnosis for a young patient suffering from chronic back pain.
      CLINICAL FEATURES: A 25-year-old patient suffered from chronic mid-thoracic pain
      and a history of scoliosis. The physical examination result was unremarkable;
      thus radiographs were obtained. A posteroanterior and lateral chest radiograph
      demonstrated a well-defined opacity extending from the region of the left hilum
      to below the diaphragm. A differential diagnosis of a posterior mediastinal mass
      was advanced. Computed tomography revealed a homogenous, nonenhancing left
      posterior mediastinal mass with adjacent posterior rib deformity. Computed
      tomography (CT)-guided biopsy subsequently defined the mass as a ganglioneuroma.
      INTERVENTION AND OUTCOME: The mass was surgically resected. Although the patient
      experienced some postsurgical discomfort, she has fared well. CONCLUSION: Twenty
      percent of mediastinal tumors are neurogenic, and 10% of neurogenic tumors are
      ganglioneuromas. In spite of the rarity of this tumor, ganglioneuroma should be
      considered in the differential diagnosis of young patients suffering from back
      pain. The diagnosis is important to ascertain because surgical resection is
      curative and can relieve the symptoms.

PMID- 11986581
TI  - Intermittent cervical traction for cervical radiculopathy caused by large-volume
      herniated disks.
AB  - OBJECTIVE: To describe the use of intermittent cervical traction in managing 4
      patients with cervical radiculopathy and large-volume herniated disks. CLINICAL
      FEATURES: Four patients had neck pain radiating to the arm. The clinical
      examination was typical in all cases for radiculopathy of cervical origin.
      Magnetic resonance imaging (MRI) of the cervical spine revealed large-volume
      herniated disks in all patients. INTERVENTIONS AND OUTCOME: The treatment
      consisted of intermittent on-the-door cervical traction under the supervision of
      our physiotherapists. Complete symptom resolution for each patient occurred
      within 3 weeks. One patient who had an episode of recurrence 16 months after the
      first treatment was successfully managed again with cervical traction and
      physiotherapy. CONCLUSION: Cervical spine traction could be considered as a
      therapy of choice for radiculopathy caused by herniated disks, even in cases of
      large-volume herniated disks or recurrent episodes.

PMID- 11986582
TI  - The role of the institution in developing the next generation chiropractor:
      clinician and researcher.

PMID- 11986583
TI  - Rating specific chiropractic technique procedures for common low back conditions.

PMID- 11986584
TI  - The use and role of sport chiropractors in the national football league: a short
      report.
AB  - OBJECTIVE: To analyze chiropractic utilization on National Football League (NFL)
      medical teams and the role played by chiropractors. DESIGN: Postal survey of head
      athletic trainers of the 36 teams. Survey questions were developed from responses
      to a questionnaire submitted to a pilot group of 30 sport chiropractors and a
      panel of 20 postdoctoral faculty of the sport chiropractic program of the
      American Chiropractic Board of Sport Physicians, as well as a representative from
      the University of South Alabama. RESULTS: Twenty-two of 36 questionnaires were
      returned for a return rate of 66%. Of the trainers who did respond, 45% have
      personally been treated by a chiropractor, and 55% have not. Seventy-seven
      percent of the trainers have referred to a chiropractor for evaluation or
      treatment, and 23% have not. Thirty-one percent of NFL teams use a chiropractor
      in an official capacity on their staffs, and 69% do not. When asked to identify
      conditions appropriate for referral to a chiropractor, the respondents identified
      low back pain (61%), "stingers" and "burners" usually associated with neck injury
      (31%), headaches (8%), asthma or other visceral disorders (0%). All respondents
      (100%) agree that some players use chiropractic care without referral from team
      medical staff. CONCLUSION: There is significant chiropractic participation in US
      professional football. Certified athletic trainers see a role for the sport
      chiropractor in the NFL, primarily as a spinal specialist treating low back and
      other musculoskeletal injuries. A substantial majority of NFL trainers have
      developed cooperative relationships with chiropractors, with 77% having referred
      a player to a chiropractor. Thirty-one percent of NFL teams have a chiropractor
      officially on staff, and an additional 12% of teams refer players to
      chiropractors but do not directly retain these chiropractors.

PMID- 11986585
TI  - Surgical substrates of postoperative junctional ectopic tachycardia in congenital
      heart defects.

PMID- 11986586
TI  - Mathematic modeling and cardiac surgery.

PMID- 11986587
TI  - Temperature management after hypothermic circulatory arrest.

PMID- 11986588
TI  - Surgical substrates of postoperative junctional ectopic tachycardia in congenital
      heart defects.
AB  - BACKGROUND: Junctional ectopic tachycardia is a major cause of postoperative
      morbidity after surgery for congenital cardiac disease. To elucidate the
      mechanism of junctional ectopic tachycardia, surgical correlations were studied
      in four types of congenital heart defects involving closure of a ventricular
      septal defect, relief of right ventricular outflow tract obstruction, or both.
      METHODS: Between 1997 and 1999, a total of 343 consecutive patients underwent
      repair of tetralogy of Fallot (n = 114), common truncus arteriosus (n = 10),
      ventricular septal defect (n = 161), and atrioventricular septal defect (n = 58).
      Variables studied included demographic and bypass data, surgical approaches
      toward ventricular septal defect closure and relief of right ventricular outflow
      tract obstruction, and resection as opposed to division of muscle bundles.
      RESULTS: Junctional ectopic tachycardia occurred most frequently after repair of
      tetralogy of Fallot (n = 25; 21.9%), with no cases occurring after repair of
      common trunk, 6 occurring after repair of ventricular septal defect (3.7%), and 6
      occurring after repair of atrioventricular septal defect (10.3%). Stepwise
      logistic regression revealed that resection of muscle bundles (P <.0001), higher
      bypass temperatures (P <.03), and relief of right ventricular outflow tract
      obstruction through the right atrium (P <.05) significantly and independently
      predicted postoperative junctional ectopic tachycardia. CONCLUSIONS: Relief of
      right ventricular outflow tract obstruction appears to be more important in the
      causation of junctional ectopic tachycardia than does ventricular septal defect
      closure, which may explain the higher incidence of this complication after
      tetralogy of Fallot repair. Muscular resection seems to be more arrhythmogenic
      than is simple division. Increased traction through the right atrium for relief
      of right ventricular outflow tract obstruction would fit the hypothesis that
      enhanced automaticity of the His bundle, the morphologic substrate for junctional
      ectopic tachycardia, may result from direct trauma or infiltrative hemorrhage of
      the conduction system. When feasible, techniques avoiding both extensive muscle
      resection and excessive traction should be applied during resection of right
      ventricular outflow tract obstruction.

PMID- 11986589
TI  - Neurodevelopmental outcomes after biventricular repair of congenital heart
      defects.
AB  - OBJECTIVE: This study was undertaken to assess neurodevelopment of children after
      biventricular repair of congenital heart defects. METHODS: Full-scale,
      performance, and verbal IQs of 69 patients who had undergone biventricular repair
      were assessed at 5 years of age with the Wechsler Preschool and Primary Scales of
      Intelligence-Revised. The Wide Range Assessment of Visual-Motor Abilities was
      used to measure visual-motor skills. Regression analyses adjusting for parental
      IQ and socioeconomic status were used to evaluate outcome predictors. RESULTS:
      Median age at repair was 91 days (range 1-1558 days). Hypothermic circulatory
      arrest was used in 35 cases (mean duration of hypothermic circulatory arrest 33
      +/- 17 minutes). Mean full-scale, performance, and verbal IQs for the entire
      study population were within the reference range (full-scale 96.9 +/- 15.9,
      performance 96.6 +/- 16.8, verbal 97.7 +/- 15.2). Anatomic diagnosis, age at
      operation, and use of hypothermic circulatory arrest did not influence full-scale
      IQ (P =.66, P =.14, and P =.46, respectively), performance IQ (P =.64, P =.36,
      and P =.73, respectively), or verbal IQ (P =.74, P =.08, and P =.39,
      respectively). Among patients subjected to hypothermic circulatory arrest,
      duration of arrest was evaluated as a predictor of outcome. After adjustment for
      parental IQ, full-scale (P =.12), performance (P =.07), and verbal (P =.22) IQ
      scores of patients with more than 39 minutes of hypothermic circulatory arrest
      were not different from those of patients who had arrest periods of 39 minutes or
      less. After adjustment for socioeconomic status, however, full-scale (P =.05) and
      performance (P =.03) IQ scores were lower among patients who had more than 39
      minutes of hypothermic circulatory arrest. After adjustment for either parental
      IQ or socioeconomic status, patients with more than 39 minutes of arrest had
      lower scores on Wide Range Assessment of Visual-Motor Abilities subtests of
      visual-motor and fine motor abilities and on several performance IQ subtests.
      CONCLUSIONS: IQs of patients who had undergone biventricular repair of congenital
      heart defects were within the reference range. However, hypothermic circulatory
      arrest for longer than 39 minutes was associated with deficits in visual-motor
      and fine motor skills and possibly in full-scale IQ.

PMID- 11986590
TI  - Total right ventricular exclusion procedure: an operation for isolated congestive
      right ventricular failure.
AB  - OBJECTIVE: To prevent possible deleterious effects of right ventricular volume
      overload on cardiorespiratory function, we developed a total right ventricular
      exclusion procedure for the treatment of end-stage isolated congestive right
      ventricular failure. METHODS: Since 1996, this procedure has been performed in 5
      patients in New York Heart Association functional class IV: 2 adults with
      arrhythmogenic right ventricular dysplasia and 3 children with Ebstein anomaly.
      The entire right ventricular free wall was resected along the atrioventricular
      groove and then parallel to the interventricular septum, sparing the pulmonary
      valve and a skeletonized right coronary artery. The orifice of the tricuspid
      valve was closed with either a polytetrafluoroethylene patch or with its
      leaflets. The defect of the right ventricular free wall was covered with a
      polytetrafluoroethylene patch in the 2 patients with arrhythmogenic right
      ventricular dysplasia and directly closed with the remnant of the free wall in
      the 3 children with Ebstein anomaly. After resection of a redundant right atrial
      wall, coronary sinus blood flow was rerouted into the left atrium through an
      atrial septal defect. A total cavopulmonary connection was constructed in 4
      patients and a bidirectional superior cavopulmonary anastomosis in 1 infant. The
      heart was controlled with a DDD pacemaker in 3 patients. RESULTS: The patients
      were extubated at a mean of 14 hours postoperatively (range, 1-38 hours). There
      were no early or late deaths. At follow-up, ranging from 8 to 57 months, the mean
      cardiothoracic ratio had decreased from 74% +/- 7% before the operation to 52% +/
      6% (P <.01). All patients are in functional class I. Neither of the patients
      with arrhythmogenic right ventricular dysplasia have had attacks of ventricular
      tachycardia nor are they using antiarrhythmic medication. CONCLUSIONS: The total
      right ventricular exclusion procedure provides effective decompression of the
      lung, as well as the left ventricle, and may result in more effective volume
      loading of a surgically created single ventricle with increased systemic output.
      We believe that this new surgical option offers rescue treatment for isolated end
      stage right ventricular failure in critically ill patients.

PMID- 11986591
TI  - Cardiac surgery with deep hypothermic circulatory arrest produces less systemic
      inflammatory response than low-flow cardiopulmonary bypass in newborns.
AB  - OBJECTIVE: We sought to compare low-flow cardiopulmonary bypass with deep
      hypothermic circulatory arrest in respect to the influence on the systemic
      inflammatory response. METHODS: Twenty-three infants weighing less than 10 kg and
      scheduled for repair of congenital malformations were enrolled in a randomized,
      controlled study. Eleven patients underwent cardiac surgery with deep hypothermic
      circulatory arrest (the DHCA group). Low-flow cardiopulmonary bypass was used in
      another 12 patients (the LF group). Interleukin 6 and 8 and anaphylatoxin C3a
      levels were measured 6 times perioperatively. Also, perioperative weight gain and
      a radiologic soft-tissue index were compared. RESULTS: All patients had an
      uneventful clinical course. Duration of deep hypothermic circulatory arrest was
      40 +/- 4 minutes; the bypass time was significantly shorter in the DHCA group (85
      +/- 8 vs 130 +/- 19 minutes). However, the duration of the operation was similar
      in both groups (245 +/- 30 vs 246 +/- 30 minutes). During cardiopulmonary bypass
      (rewarming), the concentration of C3a (3751 +/- 388 vs 5761 +/- 1688 ng/mL, mean
      +/- SEM) was significantly lower in the DHCA group than in the LF group. The
      interleukin 8 level was significantly lower, and the interleukin 6 level had a
      tendency to be lower in the DHCA group compared with levels in the LF group.
      There was less weight gain on the first postoperative day in the DHCA group (65
      +/- 61 vs 408 +/- 118 g). The soft-tissue index suggested reduced edema formation
      in the DHCA group. CONCLUSION: Deep hypothermic circulatory arrest produces less
      systemic inflammatory response than low-flow cardiopulmonary bypass. In addition,
      there is an indication of less fluid accumulation postoperatively.

PMID- 11986592
TI  - Cavopulmonary anastomosis induces pulmonary expression of the angiotensin II
      receptor family.
AB  - BACKGROUND: Cavopulmonary anastomosis is used for palliation of cyanotic cardiac
      lesions. Postoperative development of pulmonary arteriovenous malformations can
      be significant in 10% to 25% of patients. To study the basis for formation of
      arteriovenous malformations, we developed an ovine model that reliably induces
      their development 8 weeks after cavopulmonary anastomosis. Previously, we found
      that cavopulmonary anastomosis inhibits the expression of pulmonary angiotensin
      converting enzyme and suppresses angiotensin II production. OBJECTIVE: This study
      examines the role of the angiotensin II receptors, type 1 and type 2, in this
      setting of pulmonary vascular remodeling. METHODS: Lambs, aged 40 to 50 days,
      underwent cavopulmonary anastomosis. In age-matched control animals, a sham
      operation was performed. Messenger RNA and protein expression in lung specimens
      was measured at successive time points after cavopulmonary anastomosis or sham
      operations (n = 3 at each time point). RESULTS: Angiotensin type 1 mRNA was
      maximally upregulated 2-fold at 5 weeks after cavopulmonary anastomosis (P
      =.006). Expression of angiotensin type 1 protein was increased at least 2-fold at
      2, 5, and 15 weeks after cavopulmonary anastomosis (P =.005). Cavopulmonary
      anastomosis also increased angiotensin type 2 mRNA and protein expression at
      least 2-fold at 2 and 5 weeks (P =.02) after surgical intervention. At 15 weeks,
      expression of angiotensin type 2 mRNA and protein was unchanged from that seen in
      control animals. Immunolocalization in pulmonary tissue sections 2 weeks after
      cavopulmonary anastomosis revealed markedly enhanced staining of angiotensin II
      receptor type 1 in vascular smooth muscle and angiotensin II receptor type 2 in
      the endothelium of pulmonary arteries. CONCLUSIONS: Rapid elevation in the
      expression of the type 1 and 2 angiotensin II receptors in the affected pulmonary
      vasculature after cavopulmonary anastomosis suggests their involvement in the
      pathologic vascular remodeling that occurs after cavopulmonary anastomosis.

PMID- 11986593
TI  - Preoperative prediction of the risk of pulmonary complications after
      esophagectomy for cancer.
AB  - OBJECTIVES: Pulmonary complication is a frequent morbid event after esophagectomy
      for cancer. Its prediction may help select patients for preoperative
      rehabilitation. METHODS: We performed a retrospective review of 292 patients (231
      men and 61 women; mean age, 60.1 years) who underwent esophagectomy for cancer
      between 1980 and 2000. Data were analyzed to identify factors associated with the
      development of pulmonary complications (reintubation for isolated respiratory
      failure and pneumonia). A scoring system was developed, and its ability to
      predict complications was assessed. RESULTS: Resection was performed for squamous
      cancer (n = 100), adenocarcinoma (n = 186), and other histologic types (n = 6) in
      patients with stages 0 or I (n = 53), II (n = 94), III (n = 114), and IV (n = 23)
      disease. Pulmonary complications, which developed in 78 (27%) patients, were
      associated with a 4.5-fold increase in operative mortality (7%-32%).
      Multivariable analysis identified independent predictors of pulmonary
      complications to be patient age (odds ratio [OR], 1.31; 95% confidence interval
      [CI], 0.99-1.74; P =.059), percentage forced expiratory volume in 1 second (OR,
      1.21; 95% CI, 1.07-1.38; P =.003), and possibly performance status (OR, 1.48; 95%
      CI, 0.88-2.50; P =.14). A scoring system using these 3 covariates was developed,
      which predicted incremental risk of pulmonary complications (P =.013). The
      incremental risks of cardiovascular and overall cardiopulmonary complications
      were also predicted with this scoring system (P <.01 for each). CONCLUSIONS: A
      scoring system using patient age, spirometry, and performance status helps
      predict the likelihood of pulmonary and cardiovascular complications after
      esophagectomy and can help select patients who may benefit from preoperative
      cardiopulmonary rehabilitation.

PMID- 11986594
TI  - Results of en bloc resection for bronchogenic carcinoma with chest wall invasion.
AB  - OBJECTIVE: Lung cancer invading the chest wall without lymph node metastasis has
      recently been downstaged to stage IIb. To validate this reclassification, we
      reviewed our experience with en bloc lung and chest wall resection for
      bronchogenic carcinoma. METHODS: From February 1985 to November 1999, 95 en bloc
      lung and chest wall resections were performed on 94 patients (62 men and 32
      women). The median age was 66 years (range, 38-93 years). Pancoast tumors were
      excluded. Factors that may affect survival were analyzed with univariate
      analysis, and factors found to be significant univariately were analyzed
      multivariately to determine whether the significant association remained after
      adjusting for other significant factors. RESULTS: Presenting symptoms included
      chest wall pain in 42 patients, cough in 17 patients, and "other" in 16 patients.
      Twenty patients were asymptomatic. Ninety-two patients were current or former
      smokers (median pack-years, 50; range, 8-150 pack-years). Seventy-five
      lobectomies, 12 pneumonectomies, 5 bilobectomies, 2 wedge excisions, and 1
      segmentectomy were performed. The number of ribs resected ranged from 1 to 5
      (median, 3). Sixty-one patients required chest wall reconstruction (prostheses in
      60 and bovine pericardium in 1). Operative morbidity and mortality were 44.2% and
      6.3%, respectively. Sixty-five cancers were classified as T3 N0 M0, 16 as T3 N1
      M0, and 14 as T3 N2 M0. Squamous cell carcinoma was present in 56 tumors,
      adenocarcinoma in 25, large cell carcinoma in 11, and "other" in 3. Follow-up was
      complete in 86 (96.6%) of 89 operative survivors and ranged from 1 month to 15
      years (median, 19 months). Overall 5-year actuarial survival was 38.7%. Five-year
      survival for patients with stage IIb disease (T3 N0 M0) was 44.3% compared with
      only 26.3% for those with stage IIIa disease (T3 N1 M0 or T3 N2 M0, P =.0082).
      Women had a better 5-year survival than men (52.9% vs 31.0%, P =.0122). The best
      5-year survival was observed in women with stage IIb disease (61.2%). All other
      variables (age, tumor size, histopathology, forced expiratory volume in 1 second,
      extent of operation, depth of invasion, and adjuvant therapy) did not
      significantly affect survival. CONCLUSIONS: En bloc resection of lung cancer
      invading the chest wall is safe but associated with significant morbidity. Long
      term survival is stage and sex dependent. The best survival is observed in women
      who have T3 N0 M0 disease (stage IIb).

PMID- 11986595
TI  - En bloc resection of non-small cell lung cancer invading the thoracic inlet and
      intervertebral foramina.
AB  - OBJECTIVE: In patients with non-small cell lung cancer invading the thoracic
      inlet, the transcervical approach does not permit removal of tumor in the
      intervertebral foramina. We report a variant that lifts this limitation. METHODS:
      Through the transcervical approach, resectability was assessed and tumor-bearing
      structures were removed, leaving tumor-free margins. Standard upper lobectomy was
      performed, leaving the lobe in place. A posterior midline approach was used for
      multilevel unilateral laminectomy, nerve root division inside the spinal canal,
      and vertebral body division along the midline. The tumor was removed en bloc with
      the lung, ribs, and vessels through the posterior incision. Fixation of the spine
      was performed. Medical charts of patients treated with this technique between
      October 1994 and April 2001 were reviewed retrospectively. RESULTS: Seventeen
      patients (mean age 45 years) were treated. Resection of the upper lobe and T1
      root was done in all 17 cases; 3- and 4-level hemivertebrectomies were done in 13
      and 3 cases, respectively; 2-level total vertebral body resection and 2-level
      hemivertebrectomy were done in 1 case; and resections of the phrenic nerve and
      subclavian artery were done in 7 and 6 patients, respectively. There were no
      perioperative deaths or residual neurologic impairments. Postoperative
      complications were pneumonia (n = 6), cerebrospinal fluid leakage (n = 1), wound
      breakdown (n = 1), and bleeding necessitating reoperation (n = 1). The overall 3-
      and 5-year survivals were 39% and 20%, respectively. CONCLUSIONS: Non-small cell
      lung cancers invading the thoracic inlet and intervertebral foramina can be
      removed completely through a combined anterior transcervical and posterior
      midline approach, with good results.

PMID- 11986596
TI  - Pharmacokinetics of paclitaxel administered by hyperthermic retrograde isolated
      lung perfusion techniques.
AB  - OBJECTIVE: Although paclitaxel is widely used as a systemic agent for the
      treatment of solid tumors, limited information is available concerning
      administration of this taxane by regional techniques. The present study was
      undertaken to evaluate the pharmacokinetics and acute toxicity of paclitaxel
      administered by hyperthermic retrograde isolated lung perfusion techniques to
      ascertain its potential for the regional therapy of unresectable pulmonary
      neoplasms. METHODS: Adult sheep underwent 90 minutes of retrograde isolated lung
      perfusion with escalating doses of paclitaxel and moderate hyperthermia using a
      protein-free, oxygenated extracorporeal circuit and a steady perfusion pressure
      of 14 to 16 mm Hg. An additional animal received paclitaxel by means of 1-hour
      central venous infusion. Paclitaxel concentrations in lung tissues, perfusates,
      and systemic circulation were determined by high-performance liquid
      chromotography techniques. Cytotoxicity of paclitaxel in cancer cells and in
      normal human bronchial epithelial cells was evaluated in vitro using 4, 5
      dimethylthiazo-2-yl-25-dipagnyl tetrazolium bromide assays. Lung tissues were
      examined by hematoxylin-and-eosin techniques. RESULTS: Paclitaxel concentrations
      (maximum concentration and area under the plasma concentration time curve) in
      perfused tissues increased with escalating perfusate doses. Uptake of drug into
      lung parenchyma appeared saturable at high paclitaxel exposure; a substantial
      pharmacokinetic advantage was observed. Paclitaxel concentrations in systemic
      circulation were undetectable or exceedingly low after perfusion. Histopathologic
      examination of lung tissues harvested 3 hours after completion of isolated lung
      perfusion revealed no immediate toxicity, even at a paclitaxel exposure 20-fold
      higher than that achievable after 1 hour of intravenous administration at the
      maximum tolerable dose in human subjects. Moderate hyperthermia enhanced
      paclitaxel-mediated cytotoxicity 5- to 100-fold in cultured cancer lines. No
      paclitaxel toxicity was observed in cultured normal human bronchial epithelial
      cells after exposure to paclitaxel under normothermic or hyperthermic conditions.
      CONCLUSIONS: These data support further evaluation of paclitaxel administered by
      hyperthermic retrograde isolated lung perfusion techniques for the treatment of
      unresectable malignant pulmonary tumors.

PMID- 11986597
TI  - A prematurely terminated phase III trial of intraoperative intrapleural hypotonic
      cisplatin treatment in patients with resected non-small cell lung cancer with
      positive pleural lavage cytology: the incidence of carcinomatous pleuritis after
      surgical intervention.
AB  - BACKGROUND: The prognosis of patients with resected non-small cell lung cancer
      without carcinomatous pleuritis whose intrapleural cancer cells were detected by
      means of a cytologic examination of pleural lavage fluid obtained immediately
      after a thoracotomy has been reported to be poor. METHODS: The Japan Clinical
      Oncology Group conducted a phase III trial for a 3-year period starting from
      October 1994 to determine whether intraoperative intrapleural hypotonic cisplatin
      treatment could effectively control pleural disease and thereby prolong the
      survival of these patients. The patients were randomized to receive either
      intraoperative intrapleural hypotonic cisplatin treatment or no treatment before
      closure of the open thorax. The intraoperative intrapleural hypotonic cisplatin
      treatment consisted of exposing the entire thorax to cisplatin (50 microg/mL) in
      distilled water for 15 minutes. RESULTS: Because of the slow registration pace,
      the study was prematurely terminated in January 1998. During the 41-month period
      from the start of the registration, 49 patients were entered into the study, and
      all were eligible. Twenty-five and 24 patients were randomly assigned to the
      treatment and control groups, respectively. No statistically significant
      difference in the overall survival and disease-free survival between the 2 groups
      was observed. However, the appearance of carcinomatous pleuritis was suppressed
      by the hypotonic cisplatin treatment (42% of the control group vs 8% of the
      treatment group, P =.008). CONCLUSIONS: Although the randomized trial was
      prematurely terminated, the intraoperative intrapleural hypotonic cisplatin
      treatment was found to effectively suppress the appearance of carcinomatous
      pleuritis in resected patients who demonstrated a positive pleural lavage
      cytology finding.

PMID- 11986598
TI  - Reverse remodeling and improved regional function after repair of left
      ventricular aneurysm.
AB  - BACKGROUND: Changes in regional left ventricular mechanics after anteroapical
      aneurysm repair in human subjects can be studied noninvasively by means of
      magnetic resonance tagging. We hypothesized that left ventricular intramyocardial
      function would improve throughout the left ventricle after repair. METHODS: We
      studied 6 male patients with a left ventricular anteroapical aneurysm (mean age
      +/- SD, 63 +/- 5 years) using magnetic resonance tagging 3 +/- 1 weeks before and
      6 +/- 1 weeks after aneurysm repair, coronary artery bypass grafting, and mitral
      valve repair (n = 2). Breath-hold tagged imaging spanned the left ventricle in
      the short axis from apex to base. Left ventricular mass, end-diastolic and end
      systolic volume, and ejection fraction were measured. Two-dimensional strain
      analysis was applied; averaged for the apical, middle, and basal left ventricle
      and the whole left ventricle; and expressed as greatest lengthening (similar to
      wall thickening), greatest shortening, and angular deviation of the lengthening
      strain from the radial direction. RESULTS: After aneurysm repair, left
      ventricular mass decreased from 373 +/- 27 to 333 +/- 25 g (P <.05), end
      diastolic volume from 212 +/- 22 to 168 +/- 18 mL (P <.005), and end-systolic
      volume from 188 +/- 26 to 113 +/- 18 mL (P <.005); ejection fraction improved
      from 13% +/- 4% to 23% +/- 4% (P <.005). For the whole left ventricle,
      lengthening strain increased from before to after the operation (8% +/- 1% to 10%
      +/- 1%, P <.01). Most of the improved lengthening occurred at the middle left
      ventricle (8% +/- 1% to 11% +/- 1%, P <.01), in the base (8% +/- 1% to 10% +/-
      1%, P <.05), and in the inferior wall (9% +/- 1% to 12% +/- 1%, P <.05).
      Lengthening tended to become more radially oriented, decreasing from 31 degrees
      +/- 3 degrees to 27 degrees +/- 3 degrees (P =.10). Shortening strain did not
      change (10% +/- 1% to 11% +/- 1%, P = not significant). CONCLUSIONS: Left
      ventricular aneurysm repair is associated with reverse remodeling and an
      improvement in the extent and orientation of intramyocardial function, especially
      at the middle and basal left ventricle and inferior wall.

PMID- 11986599
TI  - Randomized trial comparing partial versus complete chordal-sparing mitral valve
      replacement: effects on left ventricular volume and function.
AB  - OBJECTIVE: The merits of retaining the subvalvular apparatus during mitral valve
      replacement for chronic mitral regurgitation have been demonstrated in numerous
      retrospective clinical investigations but not in a randomized study. In this
      report we analyzed the early and late effects of complete versus partial chordal
      preservation on left ventricular mechanics. METHODS: Forty-seven patients
      undergoing isolated surgical correction of mitral insufficiency were
      prospectively randomized to either total or partial chordal-sparing mitral valve
      replacement. Complete data from 36 patients were available for analysis. Of these
      individuals, 15 had preservation of the posterior leaflet only (P-MVR group), and
      21 had complete preservation of all chordal structures (C-MVR group).
      Echocardiography was performed preoperatively, at the time of discharge, and
      after 1 year to determine dimensions, wall stress, left ventricular mass, and
      ejection function. RESULTS: End-diastolic volume decreased in both groups
      initially but continued to decline only in the C-MVR cohort. Similarly, although
      end-systolic volume decreased over time with total chordal preservation, no
      notable changes were observed in the P-MVR group. In the C-MVR group, end
      systolic stress decreased initially but rose slightly by 1 year. In contrast, end
      systolic stress remained unchanged at discharge in the P-MVR group and increased
      at 1 year. In terms of systolic performance, ejection fraction declined after
      surgical intervention with partial chordal-sparing techniques and did not improve
      by 1 year. Ejection fraction returned to the preoperative level after an initial
      decrease in the C-MVR group. Finally, left ventricular mass was reduced in the C
      MVR cohort versus no change in the P-MVR group. CONCLUSION: Complete retention of
      the mitral subvalvular apparatus during mitral valve replacement confers a
      significant early advantage by reducing left ventricular chamber size and
      systolic afterload compared with partial chordal preservation. Furthermore, left
      ventricular ejection performance continues to improve over time, probably because
      of more favorable left ventricular remodeling.

PMID- 11986600
TI  - Better anticoagulation control improves survival after valve replacement.
AB  - OBJECTIVE: We sought to assess the effect of anticoagulation control on long-term
      survival after valve replacement with the Medtronic Hall valve (Medtronic, Inc,
      Minneapolis, Minn). METHODS: Prospective follow-up data, including 82,297
      international normalized ratios, were collected for 1476 patients undergoing
      single valve replacement with the Medtronic Hall valve between 1979 and 1994,
      with follow-up to the end of 1998. After excluding 204 patients who either died
      within 30 days or had fewer than 10 international normalized ratios recorded
      beyond 30 days, there were 10,203 patient years of follow-up for analysis.
      Anticoagulation variability was measured as the percentage of international
      normalized ratios outside a target range of 2.0 to 4.0 for each patient. RESULTS:
      Linearized rates for late death rose progressively with increasing deciles of
      anticoagulation variability for both aortic and mitral valve replacement (2.7%
      and 3.3% per year, respectively, in deciles 1 and 2 up to 9.5% and 14.6% per
      year, respectively, in deciles 6-10; P <.001). Survival at 15 years after aortic
      valve replacement was 59% for low anticoagulation variability (deciles 1 and 2),
      55% for intermediate anticoagulation variability (decile 3), and 28% for high
      anticoagulation variability (deciles 4-10); survivals at 15 years after mitral
      valve replacement were 56%, 42%, and 24%, respectively (P <.001 between low
      intermediate anticoagulation variability and high anticoagulation variability for
      both aortic and mitral valve replacement). On multivariate analysis, significant
      predictors of reduced survival were anticoagulation variability per 20% increase
      (hazard ratio, 1.8), diabetes (hazard ratio, 1.6), decade of age (hazard ratio,
      1.6), concomitant coronary artery bypass grafting (hazard ratio, 1.5), male sex
      (hazard ratio, 1.4), hypertension (hazard ratio, 1.4), New York Heart Association
      class III or IV (hazard ratio, 1.3), and non-sinus rhythm (hazard ratio, 1.2).
      Patients with low anticoagulation variability who were in sinus rhythm and did
      not have diabetes, coronary bypass grafting, or hypertension had survivals equal
      to those of the age- and sex-matched general population at 15 years. The
      incidence of valve-related deaths was significantly higher with high
      anticoagulation variability compared with the incidence with low-intermediate
      anticoagulation variability for both aortic (1.4% vs 0.5% per year, P <.001) and
      mitral valve replacement (1.5% vs 0.5% per year, P <.001). By means of univariate
      analysis, high anticoagulation variability was significantly associated with New
      York Heart Association class III or IV at 5 years postoperatively (P <.001) and
      with age of greater than 60 years at the time of the operation (P =.002).
      CONCLUSIONS: High anticoagulation variability is the most important independent
      predictor of reduced survival after valve replacement with a mechanical valve.
      Better anticoagulation control should improve survival.

PMID- 11986601
TI  - Prolonged mild hypothermia after experimental hypothermic circulatory arrest in a
      chronic porcine model.
AB  - OBJECTIVES: We sought to evaluate the potential efficacy of prolonged mild
      hypothermia after hypothermic circulatory arrest. METHODS: Twenty pigs, after a
      75-minute period of hypothermic circulatory arrest, were randomly assigned to be
      rewarmed to 37 degrees C (normothermia group) or to 32 degrees C and kept at that
      temperature for 14 hours from the start of rewarming (hypothermia group).
      RESULTS: The 7-day survival was 30% in the hypothermia group and 70% in the
      normothermia group (P =.08). The hypothermia group had poorer postoperative
      behavioral scores than the normothermia group. Prolonged hypothermia was
      associated with lower oxygen extraction and consumption rates and higher mixed
      venous oxygen saturation levels during the first hours after hypothermic
      circulatory arrest. Decreased cardiac index, lower pH, and higher partial
      pressure of carbon dioxide were observed in the hypothermia group. There was a
      trend for beneficial effect of prolonged hypothermia in terms of lower brain
      lactate levels until the 4-hour interval and of intracranial pressure until the
      10-hour interval. Postoperatively, total leukocyte and neutrophil counts were
      lower, and creatine kinase BB was significantly increased in the hypothermia
      group. At extubation, the hypothermia group had higher oxygen extraction rates
      and lower brain tissue oxygen tension. CONCLUSIONS: A 14-hour period of mild
      hypothermia after 75-minute hypothermic circulatory arrest seems to be associated
      with poor outcome. However, the results of this study suggest that mild
      hypothermia may preserve its efficacy when it is used for no longer than 4 hours,
      but the potentials of a shorter period of postoperative mild hypothermia still
      require further investigation.

PMID- 11986602
TI  - Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated
      coronary artery bypass grafting operations: does it exist?
AB  - OBJECTIVE: Operations coupled with cardiopulmonary bypass may provoke a systemic
      inflammatory response, and it has been suggested that this responses causes
      capillary leakage of proteins, edema formation, and even organ failure. However,
      capillary leak syndrome is mainly a clinical diagnosis and has not been verified
      as yet by actual demonstration of protein leakage from the circulation. We have
      therefore measured the disappearance of labeled plasma protein before and after
      cardiopulmonary bypass. METHODS: Sixteen patients scheduled for elective coronary
      artery bypass grafting were enrolled in a prospective controlled study. The
      cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis
      factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal
      complement complex C5b9 levels were determined before, during, and 3 hours after
      cardiopulmonary bypass. The transvascular escape rate of plasma protein from the
      intravascular compartment was assessed by measuring the disappearance of
      intravenously injected Evans blue dye before and during the third hour after
      cardiopulmonary bypass. RESULTS: A significant inflammatory response could be
      demonstrated by means of the 5 measured mediators after bypass. The maximal
      increase, as compared with the baseline value, was found for interleukin 6 (36
      fold). The transvascular escape rate of Evans blue dye was similar before and
      after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS: The above data
      confirm the systemic inflammatory response induced by cardiopulmonary bypass.
      Contrary to expectations, the transvascular escape rate of Evans blue dye did not
      change when comparing values before and after bypass. The data do not support the
      concept of increased protein leakage in the exchange vessels after bypass. We
      were unable to demonstrate a capillary leak syndrome.

PMID- 11986603
TI  - Limitation of thrombin generation, platelet activation, and inflammation by
      elimination of cardiotomy suction in patients undergoing coronary artery bypass
      grafting treated with heparin-bonded circuits.
AB  - OBJECTIVE: Reports evaluating the efficacy of heparin-bonded circuits to blunt
      inflammation, platelet dysfunction, and thrombin generation in response to
      cardiopulmonary bypass have varied. We hypothesized that this variability may in
      part be related to the use of cardiotomy suction, which has been demonstrated to
      reintroduce procoagulant and proinflammatory factors into the systemic
      circulation during cardiopulmonary bypass. A prospective, randomized study was
      undertaken to evaluate the specific effects of cardiotomy suction. METHODS:
      Thirty-six patients undergoing first-time, nonemergency coronary artery bypass
      grafting with cardiopulmonary bypass were randomly assigned to one of three
      treatment groups: group I, non-heparin-bonded circuits with the use of cardiotomy
      suction (n = 12); group II, Duraflo II (BCR-3500; Jostra Bentley Corp, Irvine,
      Calif) heparin-bonded circuits with cardiotomy suction (n = 12); and group III,
      Duraflo II heparin-bonded circuits without cardiotomy suction (n = 12). Thrombin
      generation, neutrophil activation (polymorphonuclear elastase), platelet
      activation (beta-thromboglobulin), and neuronal injury (neuron-specific enolase)
      were analyzed by enzyme-linked immunosorbent assays after cardiopulmonary bypass
      and compared with prebypass levels. Results are presented as mean +/- SEM.
      RESULTS: Prebypass levels of all markers were similar among treatment groups.
      However, postbypass levels were significantly and consistently highest in group I
      relative to groups II and III. Thrombin generation levels were 5.0 +/- 0.9 nmol/L
      in group I, 3.0 +/- 0.6 nmol/L in group II, and 1.5 +/- 0.1 nmol/L in group III
      (P <.05 vs group II and P <.001 vs group I). Polymorphonuclear elastase levels
      were 307 +/- 64 microg/L in group I, 128 +/- 24 microg/L in group II (P <.05 vs
      group I), and 75 +/- 14 microg/L in group III (P <.001 vs group I). beta
      Thromboglobulin levels were 2692 +/- 401 IU/mL in group I, 912 +/- 99 IU/mL in
      group II (P =.001 vs group I), and 646 +/- 133 IU/mL in group III (P =.001 vs
      group I). Neuron-specific enolase levels were 9.8 +/- 0.9 ng/mL in group I, 10.5
      +/- 1.6 ng/mL in group II, and 4.2 +/- 0.5 ng/mL in group III (P =.001 vs groups
      I and II). CONCLUSIONS: Use of cardiotomy suction resulted in significant
      increases in thrombin, neutrophil, and platelet activation, as well as the
      release of neuron-specific enolase, after cardiopulmonary bypass. Limiting
      increases in these markers would be best accomplished by eliminating cardiotomy
      suction and routinely using heparin-bonded circuits whenever possible.

PMID- 11986604
TI  - Decreased lung ischemia-reperfusion injury in rats after preoperative
      administration of cyclosporine and tacrolimus.
AB  - OBJECTIVES: Calcineurin inhibitors reduce experimental reperfusion injury in the
      liver, brain, heart, kidney, and small bowel. These studies were undertaken to
      determine whether these agents are similarly protective against lung ischemia
      reperfusion injury. METHODS: Left lungs of male rats were rendered ischemic for
      90 minutes and reperfused for as long as 4 hours. Treated animals received
      cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours
      before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was
      quantitated in terms of tissue polymorphonuclear leukocyte accumulation
      (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum
      albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate
      tissue samples were processed for nuclear protein and cytokine messenger RNA.
      RESULTS: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours
      before reperfusion reduced lung vascular permeability by 54% and 56% relative to
      control animals (P <.03). The protective effects of cyclosporine and tacrolimus
      treatment before reperfusion correlated with 42% and 43% reductions in tissue
      polymorphonuclear leukocyte (myeloperoxidase) content (P <.008) and marked
      reductions in bronchoalveolar lavage leukocyte accumulation (P <.01).
      Administration of cyclosporine or tacrolimus at the time of reperfusion or 2
      hours into the reperfusion period offered little or no protection. Animals
      treated before reperfusion also demonstrated marked reductions in nuclear factor
      kappaB activation and expression of proinflammatory cytokine messenger RNA.
      CONCLUSION: Cyclosporine and tacrolimus treatment before reperfusion was
      protective against lung ischemia-reperfusion injury in rats. The mechanism of
      these protective effects may involve the inhibition of nuclear factor kappaB, a
      central transcription factor mediating inflammatory injury. The decreased
      expression of cytokine messenger RNA indicates that both cyclosporine and
      tacrolimus may exert their protective effects at the pretranscriptional level.

PMID- 11986605
TI  - Percutaneous aortic valve replacement: an experimental study. I. Studies on
      implantation.
AB  - OBJECTIVE: The purpose of this preliminary study was to devise a new surgical
      procedure for minimally invasive aortic valve implantation with a transluminal
      technique. METHODS: The new collapsible heart valve was prepared by mounting a
      porcine aortic valve, taken from a freshly slaughtered pig, into a self
      expandable nitinol stent by means of a suture technique. The outer diameter of
      the valved stent ranged from 15 to 23 mm, and the length ranged from 21 to 28 mm.
      Before implantation in vivo, these valved stents were tested in an in vitro
      circulatory system. Only in vitro-tested valved stents with a pressure gradient
      of less than 7 mm Hg and regurgitation of I degrees or less were used for
      transluminal aortic valve implantation in vivo. Six of these valved stents were
      implanted in the descending aorta and 8 in the ascending aorta of anesthetized
      pigs. The catheter delivery system (22F) was extraperitoneally inserted through
      the left iliac artery or the infrarenal aorta. Measurements for transvalvular
      gradient, valvular opening and closure, blood-flow characteristics,
      regurgitation, and macroscopic analysis were performed at baseline and after the
      observation period (164 +/- 48 minutes). RESULTS: This preliminary study
      contained 14 animals. One animal died of ventricular fibrillation. Technical
      failure occurred in 2 pigs as a result of stent twisting. At the end of the
      observation period, the 11 successfully implanted valved stents demonstrated low
      transvalvular gradients (mean end-systolic Deltarho(max) of 5.4 +/- 3.3 mm Hg for
      the descending aorta group, 5.4 +/- 1.2 mm Hg for the supracoronary group, and
      5.4 +/- 1.1 mm Hg for the subcoronary group), which did not differ from their in
      vitro gradients. Two-dimensional echocardiography demonstrated complete valvular
      closure and opening in 5 of 5 cases. Angiography indicated only a physiologic jet
      of regurgitation (0 degrees ) in 8 animals and mild (I degrees ) regurgitation in
      3 animals. Color Doppler ultrasonography indicated no regurgitation in 5 of 5
      cases and minor paravalvular leakage in 1 case. CONCLUSION: Aortic valved stents
      can be successfully implanted without thoracotomy by using a transluminal
      catheter technique. Long-term function of the valves remains to be established.

PMID- 11986606
TI  - The St Jude Medical symmetry aortic connector system for proximal vein graft
      anastomoses in coronary artery bypass grafting.
AB  - OBJECTIVES: A new device designed to create proximal vein graft anastomoses to
      the aorta in coronary artery bypass grafting was recently developed by the St
      Jude Medical Anastomotic Technology Group (Minneapolis, Minn). This new
      anastomosis system consists of a nickel-titanium (nitinol) connector, an aortic
      cutter, and a delivery device. METHODS: The loading of the vein on the aortic
      connector and its delivery to the aorta are described. In 43 consecutive patients
      (mean age 68 +/- 10 years, age range 33-91 years), 65 proximal vein graft
      anastomoses were performed with the new system. Intraoperative flow rates were
      assessed for all grafts according to the transit time principle. RESULTS: All
      connector anastomoses were performed without the use of any aortic clamp. Times
      to complete these mechanical anastomoses were less than 10 seconds in all cases.
      Hemostasis was instantaneous in all cases, with only 3 system failures. These
      connectors were easily removed so that the anastomoses could be performed with
      standard suturing technique through the same aortotomy without complications. All
      vein grafts were patent at the end of the procedure, and there were no
      intraoperative or postoperative complications related to the device. CONCLUSIONS:
      The aortic connector system was easy to handle and allowed quick creation of
      reliable, reproducible, and uniform anastomoses. In addition, anastomoses could
      be done without any clamping of the aorta, which is especially attractive for off
      pump procedures, because aortic manipulation and therefore the risks of embolism
      and aortic dissection would be further minimized. In on-pump cases this technique
      would facilitate the single-clamp technique, again minimizing aortic
      manipulation.

PMID- 11986607
TI  - Early experience of coronary artery bypass grafting with a new self-closing clip
      device.
AB  - OBJECTIVE: We are in the midst of development of several new anastomotic devices
      for use in coronary artery bypass grafting surgery. This study was designed to
      examine one of these devices (a new self-closing clip) for left internal thoracic
      artery-left anterior descending coronary artery anastomosis. Its feasibility and
      the quality of anastomosis were evaluated. METHODS: Fourteen patients who
      underwent first-time elective coronary artery bypass surgery were enrolled
      between July and December 2000. The left internal thoracic artery was anastomosed
      to the left anterior descending coronary artery in an interrupted manner with
      Coalescent U-clips (Coalescent Surgical, Inc, Sunnyvale, Calif). Immediate
      patency was checked with a transit-time flowmeter. Selective angiography was
      performed 6 months after surgical intervention. RESULTS: Five patients underwent
      on-pump coronary bypass grafting, 9 on the beating heart. One patient was
      excluded from the study intraoperatively because of a poor target site
      necessitating a 2-cm-long anastomosis. Left internal thoracic artery-left
      anterior descending artery anastomoses were created with an average of 11.8 clips
      in 15.9 minutes. Mean graft flow was 45.6 mL/min. Neither conversion to standard
      suture technique nor revision of anastomosis was necessary. There tended to be a
      learning curve in the anastomosis on the beating heart. Postoperative lengths of
      stay in the intensive care unit and the hospital were 20.7 hours and 3.9 days,
      respectively. Neither death nor major complication was seen, except for temporary
      atrial fibrillation in 2 patients. Graft patency at 6 months was 100% (FitzGibbon
      grade A). CONCLUSION: Left internal thoracic artery-left anterior descending
      artery anastomoses can be created safely and effectively with new self-closing
      clips on the beating, as well as the arrested, heart. Midterm patency was shown
      to be perfect by means of angiography.

PMID- 11986608
TI  - Sutureless coronary anastomosis with an anastomotic device and tissue adhesive in
      off-pump porcine coronary bypass grafting.
AB  - OBJECTIVE: In the search for a facilitated coronary artery anastomosis, we
      assessed the feasibility of a hybrid anastomosis technique that used a prototype
      anastomotic device with an extraluminal frame (crinoline-like) and octyl
      cyanoacrylate adhesive. METHODS: During off-pump coronary artery bypass grafting
      in pigs (n = 8), a left internal thoracic artery-right coronary artery
      anastomosis was constructed and evaluated during the operation and at 5
      postoperative weeks. The anastomosis was examined by flow measurement,
      angiography, intraluminal cast geometric analysis, and histologic analysis.
      RESULTS: Anastomosis construction required 6.2 +/- 1.3 minutes (mean +/- SD). At
      5 weeks all anastomoses were fully patent, with minor anastomotic diameter
      narrowing (median 16%, 15th-85th percentile 16%-26%). After 30-second graft
      occlusion, median peak hyperemic flow response was 5.0 (15th-85th percentile 4.4
      6.5). As a result of complete, streamlining filling of anastomotic wall recesses
      by neointima formation, more intimal hyperplasia was found in the crinoline
      adhesive anastomoses than in sutured control anastomoses. No excessive, lumen
      narrowing neointima formation was observed, however. CONCLUSIONS: The hybrid
      coronary anastomosis technique was feasible without any need for dedicated
      application tools. If technical improvements can be realized, the hybrid
      technique may provide an alternative to manual suturing.

PMID- 11986609
TI  - Low-dose endobronchial gene transfer to ameliorate lung graft ischemia
      reperfusion injury.
AB  - OBJECTIVE: This study was undertaken to determine whether low-dose endobronchial
      transfer to the donor of the gene for human interleukin 10 would decrease
      ischemia-reperfusion injury in lung transplantation. METHODS: Experiments used
      male Fischer rats. Donor animals underwent right thoracotomy. A catheter was
      introduced into the left main bronchus, and vector was instilled. Group I (n = 6)
      received 2 x 10(7) plaque-forming units of adenovirus encoding human interleukin
      10, group II (n = 6) received an adenovirus control encoding beta-galactosidase,
      and group III (n = 6) received saline solution. After instillation the left main
      bronchus was clamped for 60 minutes. Lungs were removed 24 hours later and stored
      in low-potassium dextran glucose solution for 18 hours before left lung
      transplantation. Graft function was assessed at 24 hours immediately before the
      animals were killed. Ratio of wet to dry weight and tissue myeloperoxidase
      activity were measured. Transgenic expression of human interleukin 10 was
      evaluated by means of enzyme-linked immunosorbent assay and immunohistochemical
      assay. RESULTS: Arterial oxygenation was significantly improved in group I
      relative to groups II and III (257.6 +/- 59.7 mm Hg vs 114.6 +/- 66.9 mm Hg and
      118.6 +/- 91.1 mm Hg, P =.008 and P =.007, respectively). Neutrophil
      sequestration, as measured by myeloperoxidase activity, was also significantly
      reduced in group I relative to groups II and III (0.141 +/- 0.025 vs 0.304 +/-
      0.130 and 0.367 +/- 0.153 Delta optical density units/[min. mg protein], P =.029
      and P =.004, respectively). Enzyme-linked immunosorbent assay and
      immunohistochemical assay demonstrated the expression of human interleukin 10 in
      transfected lungs only. CONCLUSIONS: Low-dose endobronchial transfer to the donor
      of the gene for human interleukin 10 ameliorated ischemia-reperfusion injury in
      rodent lung transplantation by improving graft oxygenation and reducing
      neutrophil sequestration. Only 2 x 10(7) plaque-forming units of adenoviral
      vector were required for functional transgenic expression. Endobronchial gene
      transfer to lung grafts may be a useful delivery route even at low doses.

PMID- 11986610
TI  - Role of CD8+ lymphocytes in chronic rejection of transplanted hearts.
AB  - BACKGROUND: The contribution of CD8(+) lymphocytes to the pathogenesis of cardiac
      allograft vasculopathy, or chronic rejection in heart transplants, remains
      undefined. We used both major histocompatibility complex class I mismatched and
      major histocompatibility complex class II mismatched models of cardiac allograft
      vasculopathy to characterize the role of CD8(+) lymphocytes in the development of
      cardiac allograft vasculopathy. METHODS: Donor hearts from B10.A mice were
      transplanted into B10.BR recipients (major histocompatibility complex class I
      mismatched). Donor hearts were harvested at 1, 7, 14, and 30 days after
      transplantation and (1) quantitated morphometrically for lesion development, (2)
      stained immunohistochemically, or (3) digested for isolation of graft
      infiltrating cells. The cytotoxic phenotype of graft-infiltrating CD8(+)
      lymphocytes was determined with flow cytometry. Intracellular cytokine staining
      of CD8(+) and CD4(+) lymphocytes for interleukin 2, interferon g, interleukin 4,
      and interleukin 10 was performed with 2-color flow cytometry. Finally, B6.C
      H2(bm12) donor hearts were transplanted into either C57BL/6 wild-type (major
      histocompatibility complex class II mismatched) or CD8 -/- knockout recipients
      and examined for the development of cardiac allograft vasculopathy. RESULTS: In
      the major histocompatibility complex class I mismatched model, CD8(+) lymphocytes
      were the predominant T-lymphocyte subset that infiltrated the allografts and
      demonstrated markers of activation. The intracellular cytokine-staining assay
      demonstrated that CD8(+) lymphocytes were the primary sources of allograft
      interleukin 2 and interferon gamma. Intimal lesions developed in the allografts
      by day 14 (12.0% +/- 4.0%) and further increased by day 30 (44.0% +/- 5.0%). In
      the major histocompatibility complex class II mismatched model, the donor hearts
      in the CD8 -/- knockout recipients had substantially less severe intimal lesions
      when compared with the donor hearts in wild-type recipients (19.0% +/- 6.0% vs
      50.0% +/- 7.0%, respectively; P <.05). CONCLUSIONS: In both major
      histocompatibility complex class I and II mismatched models, CD8(+) lymphocytes
      contribute significantly to chronic rejection. The findings of this study suggest
      that control of chronic rejection requires interventions directed at CD8(+)
      lymphocytes.

PMID- 11986611
TI  - Heart transplantation with donors fifty years of age and older.
AB  - OBJECTIVE: Limited availability of donor organs has led to the progressive
      expansion of the criteria for donor selection, particularly a higher age limit of
      potential donors. We retrospectively reviewed the outcomes of patients who
      underwent heart transplantation using cardiac allografts 50 years of age and
      older and compared them with patients who had donor organs younger than 50 years.
      METHOD: Between September 1989 and May 2000, 20 patients underwent orthotopic
      heart transplantation using donor hearts 50 years of age and older (range 50-56
      years, mean 52.7 +/- 1.8 years) and were compared with 267 patients who received
      donor organs less than 50 years of age (range 9-49.9 years, mean 27.2 +/- 8.6
      years). Patient and donor criteria were identical in both groups. Follow-up was 4
      to 128 months with a mean of 37.4 +/- 2.8 months in the older donor group and
      52.6 +/- 2.4 months in the younger donor group. RESULTS: There were no
      differences between these 2 cohorts of patients regarding age, sex,
      cardiomyopathy, preoperative cytomegalovirus status, New York Heart Association
      class, and transplant status at transplantation. Donor characteristics, including
      sex, left ventricular ejection fraction, diabetes, cytomegalovirus status, and
      allograft ischemic times, were also similar in the 2 groups. Donor/recipient
      cytomegalovirus matching showed no differences as well. Thirty-day or to
      discharge operative mortality was similar in the older and younger donor groups
      (5% +/- 4.8% vs 3.5% +/- 1.1%; P =.84). Actuarial survival at 1 and 5 years was
      also similar in both groups (89.7% +/- 6.9% vs 91% +/- 1.8% and 53.1% +/- 14.7%
      vs 71.0% +/- 3.1%, respectively; P =.59). No patient in the older donor group
      required coronary artery bypass grafting or retransplantation during the follow
      up period, whereas 2 patients in the younger donor group required coronary artery
      bypass, and 5 patients underwent retransplantation (P > or =.50). Two patients in
      the older donor group died of nonspecific allograft failure, whereas 3 patients
      in the younger donor group experienced similar posttransplant complication (P >
      or =.50). CONCLUSIONS: Carefully selected donor hearts 50 years of age and older
      can be used for heart transplantation with long-term survival and related
      outcomes similar to those of younger donor organs. This use of selective cardiac
      allografts maximizes donor organ usage and expands the donor pool effectively
      without an adverse impact on long-term results.

PMID- 11986612
TI  - Facilitated anastomosis for reoperative circumflex coronary revascularization on
      the beating heart through a left thoracotomy.

PMID- 11986613
TI  - Reverse saphenous interposition vein graft repair of a giant atherosclerotic
      aneurysm of the left anterior descending coronary artery.

PMID- 11986614
TI  - Renal vein injury complicating removal of intravenous leiomyoma.

PMID- 11986615
TI  - Inflammatory aneurysm of the ascending thoracic aorta.

PMID- 11986616
TI  - Interatrial septostomy under transesophageal echocardiography guidance: a novel
      approach.

PMID- 11986617
TI  - Carotid artery patch plasty as a last resort repair for long-segment congenital
      tracheal stenosis.

PMID- 11986618
TI  - Fate of the unligated vertical vein after surgical correction with total
      anomalous pulmonary venous connection in early infancy.

PMID- 11986619
TI  - A question of terminology.

PMID- 11986620
TI  - Adaptation in the chemotactic guidance of nerve growth cones.
AB  - Pathfinding by growing axons in the developing nervous system may be guided by
      gradients of extracellular guidance factors. Analogous to the process of
      chemotaxis in microorganisms, we found that axonal growth cones of cultured
      Xenopus spinal neurons exhibit adaptation during chemotactic migration,
      undergoing consecutive phases of desensitization and resensitization in the
      presence of increasing basal concentrations of the guidance factor netrin-1 or
      brain-derived neurotrophic factor. The desensitization is specific to the
      guidance factor and is accompanied by a reduction of Ca2+ signalling, whereas
      resensitization requires activation of mitogen-associated protein kinase and
      local protein synthesis. Such adaptive behaviour allows the growth cone to re
      adjust its sensitivity over a wide range of concentrations of the guidance
      factor, an essential feature for long-range chemotaxis.

PMID- 11986621
TI  - Formation and propagation of matter-wave soliton trains.
AB  - Attraction between the atoms of a Bose-Einstein condensate renders it unstable to
      collapse, although a condensate with a limited number of atoms can be stabilized
      by confinement in an atom trap. However, beyond this number the condensate
      collapses. Condensates constrained to one-dimensional motion with attractive
      interactions are predicted to form stable solitons, in which the attractive
      forces exactly compensate for wave-packet dispersion. Here we report the
      formation of bright solitons of (7)Li atoms in a quasi-one-dimensional optical
      trap, by magnetically tuning the interactions in a stable Bose-Einstein
      condensate from repulsive to attractive. The solitons are set in motion by
      offsetting the optical potential, and are observed to propagate in the potential
      for many oscillatory cycles without spreading. We observe a soliton train,
      containing many solitons; repulsive interactions between neighbouring solitons
      are inferred from their motion.

PMID- 11986622
TI  - Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent
      MAPK activation.
AB  - Neuronal growth cones are guided to their targets by attractive and repulsive
      guidance cues. In mammals, netrin-1 is a bifunctional cue, attracting some axons
      and repelling others. Deleted in colorectal cancer (Dcc) is a receptor for netrin
      1 that mediates its chemoattractive effect on commissural axons, but the
      signalling mechanisms that transduce this effect are poorly understood. Here we
      show that Dcc activates mitogen-activated protein kinase (MAPK) signalling, by
      means of extracellular signal-regulated kinase (ERK)-1 and -2, on netrin-1
      binding in both transfected cells and commissural neurons. This activation is
      associated with recruitment of ERK-1/2 to a Dcc receptor complex. Inhibition of
      ERK-1/2 antagonizes netrin-dependent axon outgrowth and orientation. Thus,
      activation of MAPK signalling through Dcc contributes to netrin signalling in
      axon growth and guidance.

PMID- 11986623
TI  - Don't boycott Israel's scientists.

PMID- 11986624
TI  - Selling science to the young.

PMID- 11986625
TI  - Venter lays foundations for fresh career as ethical philanthropist.

PMID- 11986628
TI  - Air-travel study struggles to get airborne.

PMID- 11986629
TI  - Canadian lab loses Amgen backing.

PMID- 11986631
TI  - NASA faces legal challenge over Hawaiian telescope plan.

PMID- 11986630
TI  - Norway: Turning oil into science.

PMID- 11986632
TI  - Neutrino review will seek out 'scientific redundancy'.

PMID- 11986633
TI  - No end in sight for German misconduct probe.

PMID- 11986634
TI  - Satellite delay spells shortage of star data.

PMID- 11986635
TI  - Seed imports raise hopes of Afghan recovery.

PMID- 11986637
TI  - Dual identities.

PMID- 11986638
TI  - Snowball fights.

PMID- 11986639
TI  - Information overload.

PMID- 11986640
TI  - Don't punish scientists for government actions.

PMID- 11986641
TI  - The challenge offered by X-ray lasers.

PMID- 11986642
TI  - Intensive farming, US-style, is not sustainable worldwide.

PMID- 11986643
TI  - Challenges for taxonomy.

PMID- 11986647
TI  - Brownian ratchets: Darwin's motors.

PMID- 11986648
TI  - Something new under the sea.

PMID- 11986649
TI  - Liquid crystal painting.

PMID- 11986650
TI  - The amazing astrocyte.

PMID- 11986653
TI  - How to be invasive.

PMID- 11986654
TI  - Exciton developments.

PMID- 11986655
TI  - Modular feedback.

PMID- 11986657
TI  - Rat navigation guided by remote control.
AB  - Free animals can be 'virtually' trained by microstimulating key areas of their
      brains.

PMID- 11986658
TI  - Linguistic ability and early language exposure.
AB  - For more than 100 years, the scientific and educational communities have thought
      that age is critical to the outcome of language learning, but whether the onset
      and type of language experienced during early life affects the ability to learn
      language is unknown. Here we show that deaf and hearing individuals exposed to
      language in infancy perform comparably well in learning a new language later in
      life, whereas deaf individuals with little language experience in early life
      perform poorly, regardless of whether the early language was signed or spoken and
      whether the later language was spoken or signed. These findings show that
      language-learning ability is determined by the onset of language experience
      during early brain development, independent of the specific form of the
      experience.

PMID- 11986659
TI  - Astroglia induce neurogenesis from adult neural stem cells.
AB  - During an investigation of the mechanisms through which the local environment
      controls the fate specification of adult neural stem cells, we discovered that
      adult astrocytes from hippocampus are capable of regulating neurogenesis by
      instructing the stem cells to adopt a neuronal fate. This role in fate
      specification was unexpected because, during development, neurons are generated
      before most of the astrocytes. Our findings, together with recent reports that
      astrocytes regulate synapse formation and synaptic transmission, reinforce the
      emerging view that astrocytes have an active regulatory role--rather than merely
      supportive roles traditionally assigned to them--in the mature central nervous
      system.

PMID- 11986660
TI  - The confinement of Neptune's ring arcs by the moon Galatea.
AB  - Neptune has five narrow ring arcs, spanning about 40 degrees in longitude, which
      are apparently confined against the rapid azimuthal and radial spreading that
      normally results from inter-particle collisions. A gravitational resonance based
      on the vertical motion of the nearby neptunian moon Galatea was proposed to
      explain the trapping of the ring particles into a sequence of arcs. But recent
      observations have indicated that the arcs are away from the resonance, leaving
      their stability again unexplained. Here we report that a resonance based on
      Galatea's eccentricity is responsible for the angular confinement of the arcs.
      The mass of the arcs affects the precession of Galatea's eccentric orbit, which
      will enable a mass estimate from future observations of Galatea's eccentricity.

PMID- 11986661
TI  - Towards Bose-Einstein condensation of excitons in potential traps.
AB  - An exciton is an electron-hole bound pair in a semiconductor. In the low-density
      limit, it is a composite Bose quasi-particle, akin to the hydrogen atom. Just as
      in dilute atomic gases, reducing the temperature or increasing the exciton
      density increases the occupation numbers of the low-energy states leading to
      quantum degeneracy and eventually to Bose-Einstein condensation (BEC). Because
      the exciton mass is small--even smaller than the free electron mass--exciton BEC
      should occur at temperatures of about 1 K, many orders of magnitude higher than
      for atoms. However, it is in practice difficult to reach BEC conditions, as the
      temperature of excitons can considerably exceed that of the semiconductor
      lattice. The search for exciton BEC has concentrated on long-lived excitons: the
      exciton lifetime against electron-hole recombination therefore should exceed the
      characteristic timescale for the cooling of initially hot photo-generated
      excitons. Until now, all experiments on atom condensation were performed on
      atomic gases confined in the potential traps. Inspired by these experiments, and
      using specially designed semiconductor nanostructures, we have collected quasi
      two-dimensional excitons in an in-plane potential trap. Our photoluminescence
      measurements show that the quasi-two-dimensional excitons indeed condense at the
      bottom of the traps, giving rise to a statistically degenerate Bose gas.

PMID- 11986662
TI  - All-metallic three-dimensional photonic crystals with a large infrared bandgap.
AB  - Three-dimensional (3D) metallic crystals are promising photonic bandgap
      structures: they can possess a large bandgap, new electromagnetic phenomena can
      be explored, and high-temperature (above 1,000 degrees C) applications may be
      possible. However, investigation of their photonic bandgap properties is
      challenging, especially in the infrared and visible spectrum, as metals are
      dispersive and absorbing in these regions. Studies of metallic photonic crystals
      have therefore mainly concentrated on microwave and millimetre wavelengths.
      Difficulties in fabricating 3D metallic crystals present another challenge,
      although emerging techniques such as self-assembly may help to resolve these
      problems. Here we report measurements and simulations of a 3D tungsten crystal
      that has a large photonic bandgap at infrared wavelengths (from about 8 to 20
      microm). A very strong attenuation exists in the bandgap, approximately 30 dB per
      unit cell at 12 microm. These structures also possess other interesting optical
      properties; a sharp absorption peak is present at the photonic band edge, and a
      surprisingly large transmission is observed in the allowed band, below 6 microm.
      We propose that these 3D metallic photonic crystals can be used to integrate
      various photonic transport phenomena, allowing applications in
      thermophotovoltaics and blackbody emission.

PMID- 11986663
TI  - Single-substrate liquid-crystal displays by photo-enforced stratification.
AB  - Data visualization plays a crucial role in our society, as illustrated by the
      many displays that surround us. In the future, displays may become even more
      pervasive, ranging from individually addressable image-rendering wall hangings to
      data displays integrated in clothes. Liquid-crystal displays (LCDs) provide most
      of the flat-panel displays currently used. To keep pace with the ever-increasing
      possibilities afforded by developments in information technology, we need to
      develop manufacturing processes that will make LCDs cheaper and larger, with more
      freedom in design. Existing batch processes for making and filling LCD cells are
      relatively expensive, with size and shape limitations. Here we report a cost
      effective, single-substrate technique in which a coated film is transformed into
      a polymer-covered liquid-crystal layer. This approach is based on photo-enforced
      stratification: a two-step photopolymerization-induced phase separation of a
      liquid-crystal blend and a polymer precursor. The process leads to the formation
      of micrometre-sized containers filled with a switchable liquid-crystal phase. In
      this way, displays can be produced on a variety of substrates using current
      coating technology. The developed process may be an important step towards new
      technologies such as 'display-on-anything' and 'paintable displays'.

PMID- 11986664
TI  - Distribution of breaking waves at the ocean surface.
AB  - Surface waves play an important role in the exchange of mass, momentum and energy
      between the atmosphere and the ocean. The development of the wave field depends
      on wind, wave-wave and wave-current interactions and wave dissipation owing to
      breaking, which is accompanied by momentum fluxes from waves to currents. Wave
      breaking supports air-sea fluxes of heat and gas, which have a profound effect on
      weather and climate. But wave breaking is poorly quantified and understood. Here
      we present measurements of wave breaking, using aerial imaging and analysis, and
      provide a statistical description of related sea-surface processes. We find that
      the distribution of the length of breaking fronts per unit area of sea surface is
      proportional to the cube of the wind speed and that, within the measured range of
      the speed of the wave fronts, the length of breaking fronts per unit area is an
      exponential function of the speed of the front. We also find that the fraction of
      the ocean surface mixed by breaking waves, which is important for air-sea
      exchange, is dominated by wave breaking at low velocities and short wavelengths.

PMID- 11986665
TI  - A new phylum of Archaea represented by a nanosized hyperthermophilic symbiont.
AB  - According to small subunit ribosomal RNA (ss rRNA) sequence comparisons all known
      Archaea belong to the phyla Crenarchaeota, Euryarchaeota, and--indicated only by
      environmental DNA sequences--to the 'Korarchaeota'. Here we report the
      cultivation of a new nanosized hyperthermophilic archaeon from a submarine hot
      vent. This archaeon cannot be attached to one of these groups and therefore must
      represent an unknown phylum which we name 'Nanoarchaeota' and species, which we
      name 'Nanoarchaeum equitans'. Cells of 'N. equitans' are spherical, and only
      about 400 nm in diameter. They grow attached to the surface of a specific
      archaeal host, a new member of the genus Ignicoccus. The distribution of the
      'Nanoarchaeota' is so far unknown. Owing to their unusual ss rRNA sequence,
      members remained undetectable by commonly used ecological studies based on the
      polymerase chain reaction. 'N. equitans' harbours the smallest archaeal genome;
      it is only 0.5 megabases in size. This organism will provide insight into the
      evolution of thermophily, of tiny genomes and of interspecies communication.

PMID- 11986666
TI  - Feedback with soil biota contributes to plant rarity and invasiveness in
      communities.
AB  - Understanding the relative abundance of species in plant communities is an
      unsolved problem. Mechanisms such as competition, resource partitioning,
      dispersal ability and predation tolerance do not adequately explain relative
      abundance under field conditions. Recent work suggests that interactions between
      plants and soil microbes is important. Here I show that such interaction explains
      a significant proportion of the variance in the relative abundance of species in
      plant communities. Rare plants exhibited a relative decrease in growth on 'home'
      soil in which pathogens had had a chance to accumulate, whereas invasive plants
      benefited from interactions with mycorrhizal fungi. Some plant species accumulate
      pathogens quickly and maintain low densities as a result of the accumulation of
      species-specific pathogens, whereas others accumulate species-specific pathogens
      more slowly and do not experience negative feedback until plant densities reach
      high levels. These results indicate that plants have different abilities to
      influence their abundance by changing the structure of their soil communities,
      and that this is an important regulator of plant community structure.

PMID- 11986667
TI  - Effects of size and temperature on developmental time.
AB  - Body size and temperature are the two most important variables affecting nearly
      all biological rates and times. The relationship of size and temperature to
      development is of particular interest, because during ontogeny size changes and
      temperature often varies. Here we derive a general model, based on first
      principles of allometry and biochemical kinetics, that predicts the time of
      ontogenetic development as a function of body mass and temperature. The model
      fits embryonic development times spanning a wide range of egg sizes and
      incubation temperatures for birds and aquatic ectotherms (fish, amphibians,
      aquatic insects and zooplankton). The model also describes nearly 75% of the
      variation in post-embryonic development among a diverse sample of zooplankton.
      The remaining variation is partially explained by stoichiometry, specifically the
      whole-body carbon to phosphorus ratio. Development in other animals at other life
      stages is also described by this model. These results suggest a general
      definition of biological time that is approximately invariant and common to all
      organisms.

PMID- 11986668
TI  - Minocycline inhibits cytochrome c release and delays progression of amyotrophic
      lateral sclerosis in mice.
AB  - Minocycline mediates neuroprotection in experimental models of neurodegeneration.
      It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide
      synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although
      minocycline does not directly inhibit these enzymes, the effects may result from
      interference with upstream mechanisms resulting in their secondary activation.
      Because the above-mentioned factors are important in amyotrophic lateral
      sclerosis (ALS), we tested minocycline in mice with ALS. Here we report that
      minocycline delays disease onset and extends survival in ALS mice. Given the
      broad efficacy of minocycline, understanding its mechanisms of action is of great
      importance. We find that minocycline inhibits mitochondrial permeability
      transition-mediated cytochrome c release. Minocycline-mediated inhibition of
      cytochrome c release is demonstrated in vivo, in cells, and in isolated
      mitochondria. Understanding the mechanism of action of minocycline will assist in
      the development and testing of more powerful and effective analogues. Because of
      the safety record of minocycline, and its ability to penetrate the blood-brain
      barrier, this drug may be a novel therapy for ALS.

PMID- 11986669
TI  - Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to
      dendrites.
AB  - In cells, molecular motors operate in polarized sorting of molecules, although
      the steering mechanisms of motors remain elusive. In neurons, the kinesin motor
      conducts vesicular transport such as the transport of synaptic vesicle components
      to axons and of neurotransmitter receptors to dendrites, indicating that vesicles
      may have to drive the motor for the direction to be correct. Here we show that an
      AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor subunit-
      GluR2-interacting protein (GRIP1)--can directly interact and steer kinesin heavy
      chains to dendrites as a motor for AMPA receptors. As would be expected if this
      complex is functional, both gene targeting and dominant negative experiments of
      heavy chains of mouse kinesin showed abnormal localization of GRIP1. Moreover,
      expression of the kinesin-binding domain of GRIP1 resulted in accumulation of the
      endogenous kinesin predominantly in the somatodendritic area. This pattern was
      different from that generated by the overexpression of the kinesin-binding
      scaffold protein JSAP1 (JNK/SAPK-associated protein-1, also known as Mapk8ip3),
      which occurred predominantly in the somatoaxon area. These results indicate that
      directly binding proteins can determine the traffic direction of a motor protein.

PMID- 11986670
TI  - Rapid regulation of steroidogenesis by mitochondrial protein import.
AB  - Most mitochondrial proteins are synthesized on cytoplasmic ribosomes and imported
      into mitochondria. The imported proteins are directed to one of four
      submitochondrial compartments--the outer mitochondrial membrane, the inner
      mitochondrial membrane, the intramembraneous space, or the matrix--where the
      protein then functions. Here we show that the steroidogenic acute regulatory
      protein (StAR), a mitochondrial protein required for stress responses,
      reproduction, and sexual differentiation of male fetuses, exerts its activity
      transiently at the outer mitochondrial membrane rather than at its final resting
      place in the matrix. We also show that its residence time at this outer membrane
      and its activity are regulated by its speed of mitochondrial import. This may be
      the first example of a mitochondrial protein exerting its biological activity in
      a compartment other than that to which it is finally targeted. This system
      enables steroidogenic cells to initiate and terminate massive levels of
      steroidogenesis within a few minutes, permitting the rapid regulation of serum
      steroid hormone concentrations.

PMID- 11986671
TI  - HIV preferentially infects HIV-specific CD4+ T cells.
AB  - HIV infection is associated with the progressive loss of CD4(+) T cells through
      their destruction or decreased production. A central, yet unresolved issue of HIV
      disease is the mechanism for this loss, and in particular whether HIV-specific
      CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory
      CD4(+) T cells in infected individuals contain more HIV viral DNA than other
      memory CD4(+) T cells, at all stages of HIV disease. Additionally, following
      viral rebound during interruption of antiretroviral therapy, the frequency of HIV
      viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a
      greater extent than in memory CD4(+) T cells of other specificities. These
      findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV
      in vivo. This provides a potential mechanism to explain the loss of HIV-specific
      CD4(+) T-cell responses, and consequently the loss of immunological control of
      HIV replication. Furthermore, the phenomenon of HIV specifically infecting the
      very cells that respond to it adds a cautionary note to the practice of
      structured therapy interruption.

PMID- 11986672
TI  - Reduction of cytochrome c oxidase by a second electron leads to proton
      translocation.
AB  - Cytochrome c oxidase, the terminal enzyme of cellular respiration in mitochondria
      and many bacteria, reduces O(2) to water. This four-electron reduction process is
      coupled to translocation (pumping) of four protons across the mitochondrial or
      bacterial membrane; however, proton pumping is poorly understood. Proton pumping
      was thought to be linked exclusively to the oxidative phase, that is, to the
      transfer of the third and fourth electron. Upon re-evaluation of these data,
      however, this proposal has been questioned, and a transport mechanism including
      proton pumping in the reductive phase--that is, during the transfer of the first
      two electrons--was suggested. Subsequently, additional studies reported that
      proton pumping during the reductive phase can occur, but only when it is
      immediately preceded by an oxidative phase. To help clarify the issue we have
      measured the generation of the electric potential across the membrane, starting
      from a defined one-electron reduced state. Here we show that a second electron
      transfer into the enzyme leads to charge translocation corresponding to pumping
      of one proton without necessity for a preceding turnover.

PMID- 11986676
TI  - NTP Hepatotoxicity Studies of the Liver Carcinogen Methapyrilene Hydrochloride
      (CAS No. 135-23-9) Administered in Feed to Male F344/N Rats.
AB  - Methapyrilene hydrochloride is a histamine H(1)-receptor antagonist that was an
      active ingredient in many over-the-counter cold and allergy medications. In the
      mid- to late 1970s, studies in rats suggested that methapyrilene hydrochloride
      was a hepatocarcinogen, and the drug was removed from these preparations. In most
      cases, methapyrilene hydrochloride was replaced by pyrilamine maleate, a
      structurally similar analogue. As part of a program to investigate mechanisms of
      toxicity whereby structurally similar chemicals produce different toxicities,
      these chemicals were studied for induction of cell proliferation and protein
      alterations by two-dimensional gel electrophoresis in the liver of F344/N rats. A
      complete toxicologic evaluation was not needed for this research-oriented study.
      Rather, the goal of the present study was to provide retrospective data from
      subchronic toxicity studies with the known rat carcinogen methapyriline
      hydrochloride that could then be used to predict the potential carcinogenicity of
      unknown chemical agents and that could also be compared with similar data on the
      structural analogue pyrilamine maleate. Pyrilamine maleate differs from
      methapyrilene hydrochloride in the substitution of the thienyl ring with a
      paramethoxyphenyl ring. Pyrilamine maleate has been shown to produce an equivocal
      increase in the incidences of liver neoplasms in rats in 2-year feed studies, but
      only at 2,000 ppm, indicating that its potency, if any, to produce neoplasms is
      much less than that of methapyriline hydrochloride. The hepatocarcinogenic
      peroxisome proliferator Wy-14,643 was included in this study as a positive
      control that is known to induce cell proliferation, as well as protein
      alterations, in the liver. In the 14-week study of methapyrilene hydrochloride,
      groups of 40 male F344/N rats were given 0, 50, 100, 250, or 1,000 ppm
      methapyrilene hydrochloride, 1,000 ppm pyrilamine maleate (negative control), or
      50 ppm Wy-14,643 ( positive control) in feed. Rats in all groups were
      administered bromodeoxyuridine (BrdU) by osmotic minipump for the assessment of
      hepatocyte proliferation. Ten rats from each group were evaluated on days 15, 29,
      and 43 and at 14 weeks. At these times, samples of liver tissue were analyzed for
      evidence of cell proliferation via BrdU labeling and proliferating cell nuclear
      antigen (PCNA) labeling. There were no exposure-related deaths. Low mean body
      weights were generally observed in the 1,000 ppm methapyriline hydrochloride
      group and in the positive control group. Final mean body weights and mean body
      weight gains of rats exposed to 1,000 ppm methapyrilene hydrochloride were
      significantly less than those of the untreated control group at all time points.
      The final mean body weights of rats in the positive control group were
      significantly less than those of the untreated control group for rats evaluated
      on days 29 and 43 and at week 14; the mean body weight gains of rats in the
      positive control group were significantly less than those of the untreated
      control group on day 29 and at week 14. Feed consumption by rats exposed to 1,000
      ppm methapyrilene hydrochloride was significantly less than that by the untreated
      control group throughout the study. The predominant clinical observation related
      to methapyrilene hydrochloride exposure was thinness in rats exposed to 1,000
      ppm; this finding was first observed on day 29. On days 29 and 43 and at 14
      weeks, the absolute liver weights of rats exposed to 1,000 ppm methapyrilene
      hydrochloride were significantly less than those of the untreated control group.
      At all time points, the relative liver weights of rats exposed to 1,000 ppm
      methapyrilene hydrochloride and the absolute and relative liver weights of
      positive control rats were significantly greater than those of the untreated
      control group. No significant differences in liver weights were observed between
      the negative and untreated control groups at any time point. Hepatic lesions were
      observed predominantly in the 250 and 1,000 ppm methapyrilene hydrochloride
      groups and in the positive control group. The incidences of bile duct
      hyperplasia, hepatocyte necrosis, hepatocyte mitosis, and hepatocyte hypertrophy
      in rats in the 1,000 ppm group were significantly greater than those in the
      untreated control group at all time points. The severities of hepatocyte
      hypertrophy and hepatocyte mitosis in 1,000 ppm rats were generally mild to
      moderate; the lesions occurring in 250 ppm animals were less severe. At each time
      point, the incidence of bile duct hyperplasia in 250 ppm rats was significantly
      greater than that in the untreated control group. The incidences of hepatocyte
      mitosis on days 15 and 29 and the incidences of hepatocyte necrosis on days 29
      and 43 in rats in the 250 ppm group were significantly greater than those in the
      untreated control group. Incidences of pigmentation in the 250 and 1,000 ppm
      methapyrilene hydrochloride groups were significantly greater than those in the
      untreated control group on days 29 and 43 and at 14 weeks. In the positive
      control group, the incidences of granulomatous inflammation were significantly
      greater than those in the untreated control group on days 15, 29, and 43. The
      incidences of hepatocyte hypertrophy and hepatocyte mitosis in the positive
      control group were significantly greater than those in the untreated control
      group on days 15, 29, and 43. The incidence of hepatocyte hypertrophy was also
      significantly increased in the positive control group at 14 weeks. The severity
      of hepatocyte hypertrophy in the 1,000 ppm methapyrilene hydrochloride group was
      generally greater than that in the positive control group at each time point. In
      general, methapyriline hydrochloride produced a dramatic and sustained increase
      in hepatic cell proliferation over 14 weeks, whereas pyrilamine maleate at the
      same concentration produced few if any effects. Wy-14,643 also induced a large
      increase in cell proliferation which declined over time, as has been observed in
      previous studies. The mean BrdU labeling indexes of the 250 and 1,000 ppm
      methapyrilene hydrochloride groups were generally significantly greater than
      those of the untreated controls at all time points. In the negative control
      group, the BrdU labeling index was significantly less than that of the untreated
      control group on day 29. The BrdU labeling index in the positive control group
      was significantly greater than that of the untreated control group at all time
      points. On day 43 and at week 14, the mean PCNA labeling indexes of the 1,000 ppm
      methapyrilene hydrochloride group were significantly greater than those of the
      untreated control group. The mean PCNA labeling indexes of the negative control
      group were significantly less than those of the untreated control group on days
      29 and 43. On day 29, the mean PCNA labeling index of the positive control group
      was significantly greater than that of the untreated control group. The mitotic
      indexes of the 1,000 ppm methapyrilene hydrochloride group were significantly
      greater than those of the untreated control group at all time points. The mitotic
      indexes of the 250 ppm group were significantly greater than those of the
      untreated control group on day 43 and at week 14. At least 32 proteins underwent
      significant abundance changes at the highest exposure concentration of
      methapyrilene hydrochloride, and 39 protein changes were observed in the positive
      control group. Many, but not all, of the protein changes in the methapyrilene
      hydrochloride-exposed animals also occurred in the positive control group.
      Treatment with pyrilamine maleate produced no significant quantitative protein
      changes, as judged by the same criteria used for methapyrilene hydrochloride and
      Wy-14,643. Methapyrilene hydrochloride produced covalent modification of
      mitochondrial proteins as measured by the charge modification index. PCNA
      abundance in liver samples from the 250 and 1,000 ppm methapyrilene hydrochloride
      exposure groups on day 43 was significantly greater than that of the untreated
      control group. Results of tests for induction of mutagenicity by methapyrilene
      hydrochloride were negative in Salmonella typhimurium strains TA98, TA100,
      TA1535, and TA1537 and in L5178Y mouse lymphoma cells, with and without S9
      metabolic activation. However, positive responses were obtained in cytogenetic
      tests with cultured Chinese hamster ovary cells, in which methapyrilene
      hydrochloride induced sister chromatid exchanges and chromosomal aberrations. The
      increases in sister chromosome exchanges were obtained with and without S9, but
      chromosomal aberrations were increased only in the presence of S9. In summary,
      the significance of the increased hepatic cell proliferation and the protein
      alterations observed in this study is not definite, but may be of predictive
      value for assessing the toxicity and carcinogenicity of chemicals in preclinical
      assays. A chemical which does not produce an increase in cell proliferation or a
      large number of protein changes may be considered safer than a similar chemical
      that produces many such changes.

PMID- 11986677
TI  - NTP Toxicity Studies of Cyclohexanone Oxime Administered by Drinking Water to
      B6C3F1 Mice (CAS No. 100-64-1).
AB  - Cyclohexanone oxime is used primarily as a captive intermediate in the synthesis
      of caprolactam for the production of polycaprolactam (Nylon-6) fibers and
      plastics and also in a variety of industrial applications. Cyclohexanone oxime
      was selected for study because of the potential for human exposure and the
      interest in oximes as a chemical class. Toxicity studies of cyclohexanone oxime
      (approximately 99% pure) were carried out in male and female B6C3F1 mice; the
      compound was administered in drinking water for 2 weeks or 13 weeks. In addition,
      the genetic toxicity of cyclohexanone oxime was evaluated by determining
      mutagenicity in Salmonella typhimurium and induction of chromosomal aberrations
      in cultured Chinese hamster ovary cells in vitro, with and without S9 activation.
      The frequency of micronucleated normochromatic erythrocytes in the bone marrow
      and peripheral blood of mice from the 13-week study was also determined. In the 2
      week study, groups of five male and five female mice were given drinking water
      containing 0, 106, 312, 625, 1,250, or 2,500 ppm cyclohexanone oxime. No deaths
      occurred, and there was no decrease in weight gain in any group. No gross lesions
      were observed; there were significant increases in relative spleen weights of
      males and females in the 2,500 ppm group and increases in the relative liver
      weight of male mice exposed to 312 ppm or greater. In the 13-week studies, groups
      of 10 male and 10 female mice were given drinking water containing 625, 1,250,
      2,500, 5,000 or 10,000 ppm cyclohexanone oxime. Deaths occurred in the 10,000 ppm
      groups and weight gain was depressed in males and females given 10,000 ppm and in
      females given 5,000 ppm. There were significant increases in relative spleen
      weight at exposure levels of 5,000 and 10,000 ppm and significant increases in
      the relative liver weights of males and females that received 10,000 ppm.
      Microscopically, hematopoietic cell proliferation was observed in the spleen of
      males and females in the 5,000 and 10,000 ppm groups. Centrilobular cell
      hypertrophy was observed in the liver of males in the 2,500, 5,000, and 10,000
      ppm groups and in females in the 5,000 and 10,000 ppm groups. Olfactory
      epithelial degeneration was observed in all exposed groups. Cyclohexanone oxime
      was mutagenic in Salmonella typhimurium strain TA1535 with S9 activation only;
      results of mutagenicity testing of cyclohexanone oxime were negative in strains
      TA97, TA98, and TA100, with and without S9. Cyclohexanone oxime gave equivocal
      results in a test for induction of chromosomal aberrations in cultured Chinese
      hamster ovary cells without S9; with S9, results were negative. In vivo, no
      induction of micronuclei was noted in erythrocytes of mice treated with
      cyclohexanone oxime either for 13 weeks in drinking water or for 3 days by
      intraperitoneal injection. In summary, the major targets of cyclohexanone oxime
      toxicity are the erythrocyte, spleen, liver, and nasal epithelium. The no-effect
      level for erythrotoxicity is 2,500 ppm following 13 weeks of exposure. The no
      effect level for hematopoietic cell proliferation in the spleen is 2,500 ppm. The
      no-effect level for hepatotoxicity is 1,250 ppm for males and 2,500 ppm for
      females following 13 weeks of exposure. Some nasal olfactory epithelial
      degeneration was observed at all exposure levels; only at 625 ppm in males was
      the incidence of this lesion not significantly different from that in the
      controls. Cyclohexanone oxime was mutagenic only in Salmonella typhimurium strain
      TA1535 with S9 activation.

PMID- 11986678
TI  - NTP Toxicity Studies of Methyl Ethyl Ketoxime Administered in Drinking Water to
      F344/N Rats and B6C3F1 Mice (CAS No. 96-29-7).
AB  - Methyl ethyl ketoxime is used primarily as an antiskinning agent in alkyd coating
      resins. Methyl ethyl ketoxime was selected for study because of the potential for
      human exposure and because of interest in oximes as a chemical class. Toxicity
      studies of methyl ethyl ketoxime (greater than 99% pure) were carried out in male
      and female F344/N rats and B6C3F1 mice. The compound was administered in drinking
      water for 14 days or 13 weeks. In addition, the genetic toxicity of methyl ethyl
      ketoxime was evaluated by determining mutagenicity in Salmonella typhimurium and
      induction of sister chromatid exchanges and chromosomal aberrations in cultured
      Chinese hamster ovary cells in vitro, with and without S9 activation. The
      frequency of micronucleated normochromatic erythrocytes in the peripheral blood
      of mice from the 13-week study was also determined. In the 14-day studies, groups
      of five male and five female rats and mice were given drinking water containing
      0, 106, 312, 625, 1,250, or 2,500 ppm methyl ethyl ketoxime. The mean body weight
      gain of male rats in the 2,500 ppm group was significantly less than that of the
      controls; the final mean body weight of male mice in the 2,500 ppm group was also
      less than that of the controls. Spleen weights were increased in male and female
      rats in the 1,250 and 2,500 ppm groups. No chemical-related gross lesions were
      observed. Microscopic tissue evaluations were not performed. In the 13-week
      studies, groups of 10 male and 10 female rats were given drinking water
      containing 0, 312, 625, 1,250, 2,500, or 5,000 ppm and groups of 10 male and 10
      female mice were given drinking water containing 0, 625, 1,250, 2,500, 5,000, or
      10,000 ppm. Mean body weights and body weight gains of 2,500 and 5,000 ppm male
      rats and 10,000 ppm male and female mice were less than those of the controls;
      mean body weight gains of male rats in the 1,250, 2,500 and 5,000 ppm groups and
      females in the 2,500 and 5,000 ppm groups were also less than those of the
      controls. Hematology results of this drinking water study indicate that methyl
      ethyl ketoxime induces a methemoglobinemia and a responsive Heinz body anemia.
      Liver and spleen weights were generally significantly greater than those of the
      controls in male and female rats exposed to 1,250 ppm or greater; spleen weights
      were also increased in male and female mice in the 10,000 ppm groups. Kidney
      weights were significantly greater in male rats in the 5,000 ppm group and in
      female rats exposed to 1,250 ppm or greater than those of the controls.
      Microscopically, there were exposure-related increases in the incidences and
      severities of hematopoietic cell proliferation in the spleen at exposure
      concentrations of 625 ppm or greater in male and female rats and at 5,000 and
      10,000 ppm in male and female mice. A significant increase in the incidence of
      hematopoietic proliferation in the bone marrow was observed in rats exposed to
      625 ppm or greater. Liver Kupffer cell erythrophagocytosis and hemosiderin
      pigmentation, as well as renal tubule hemosiderin pigmentation, occurred in
      exposed rats and mice. Other lesions observed include hyperplasia of the
      transitional epithelial lining of the urinary bladder in male and female mice
      exposed to 2,500 ppm or greater and degeneration of the nasal olfactory
      epithelium in male and female rats in the 2,500 and 5,000 ppm groups, male mice
      in the 5,000 and 10,000 ppm groups, and female mice exposed to 2,500 ppm or
      greater. Methyl ethyl ketoxime is extensively metabolized and does not accumulate
      in tissues. Single gavage doses of 2.7, 27, or 270 mg/kg administered to rats
      were primarily converted to carbon dioxide, mostly in the first 24 hours after
      dosing. After intravenous administration, less radioactivity on a percentage
      basis was excreted as carbon dioxide than in the gavage study, and more of the
      administered dose was excreted in urine and as volatiles. Following dermal
      administration, significantly greater amounts of volatiles were excreted than
      after gavage or intravenous administration. The 270 mg/kg gavage dose may result
      in saturation of a metabolic pathway(s). There is some evidence that the ketoxime
      is metabolized to the ketone and, presumably, hydroxylamine. Methyl ethyl
      ketoxime was mutagenic in Salmonella typhimurium strain TA1535 when tested in the
      presence of hamster liver S9 activation enzymes; results of mutagenicity testing
      were negative in strains TA97, TA98, and TA100, with and without exogenous
      metabolic activation. No induction of sister chromatid exhanges or chromosomal
      aberrations was observed in cultured Chinese hamster ovary cells treated with
      methyl ethyl ketoxime, with or without S9, and no increase in the frequency of
      micronucleated erythrocytes was noted in peripheral blood obtained from male and
      female mice administered methyl ethyl ketoxime in drinking water for 13 weeks. In
      summary, the major target of methyl ethyl ketoxime is the erythrocyte; the no
      effect level for erythrotoxicity is 625 ppm in male rats and 312 ppm in female
      rats based on erythrocyte counts after 13 weeks of exposure. The no-effect level
      for hematopoietic toxicity is 312 ppm in rats based on erythroid cell hyperplasia
      in bone marrow and 2,500 ppm in mice based on hematopoietic cell proliferation in
      the spleen. Hematology results of this drinking water study indicate that methyl
      ethyl ketoxime induces a methemoglobinemia and a responsive Heinz body anemia.
      Methyl ethyl ketoxime was at most weakly genotoxic; it induced mutations in S.
      typhimurium under very specific conditions and increased the frequency of sister
      chromatid exchanges in cultured Chinese hamster ovary cells, but it did not
      induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese
      hamster ovary cells in vitro or increase the frequency of micronucleated
      erythrocytes in mice treated in vivo.

PMID- 11986679
TI  - NTP toxicity studies of carisoprodol (CAS No. 78-44-4) administered by Gavage to
      F344/N rats and B6C3F1 mice.
AB  - [carisoprodol structure: see text] Carisoprodol is a widely used skeletal muscle
      relaxant and analgesic and is available as a prescription drug. Comparative
      studies were conducted to determine the toxicity of carisoprodol administered in
      corn oil and in 0.5% methylcellulose by gavage. Carisoprodol plasma
      concentrations of rats and mice were measured at the end of the 13-week studies;
      single-dose plasma carisoprodol analyses were also performed. Genetic toxicity
      studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells,
      cultured Chinese hamster ovary cells, and peripheral blood erythrocytes of mice.
      Groups of 10 male and 10 female F344/N rats received 0, 100, 200, 400, 800, or
      1,600 mg carisoprodol per kilogram body weight in corn oil by gavage or 0, 100,
      200, 400, or 800 mg/kg carisoprodol in 0.5% methylcellulose by gavage for 13
      weeks. Groups of 10 male and 10 female B6C3F1 mice received 0, 75, 150, 300, 600,
      or 1,200 mg/kg carisoprodol in corn oil by gavage or 0, 600, 1,200, or 1,600
      mg/kg carisoprodol in 0.5% methylcellulose by gavage for 13 weeks. Among rats
      that received carisoprodol in corn oil, survival was similar to that of the
      vehicle controls. Survival of rats administered carisoprodol in 0.5%
      methylcellulose was also similar to that of the vehicle controls after adjustment
      for deaths (two males and one female in the 800 mg/kg group and two females in
      the 400 mg/kg group). The final mean body weight gain of males administered 1,600
      mg/kg carisoprodol in corn oil was significantly less than that of the vehicle
      controls; the final mean body weights and body weight gains of female rats in the
      800 and 1,600 mg/kg groups were significantly greater. In the carisoprodol in
      0.5% methylcellulose study, males in the 200 mg/kg group and females in the 100
      and 800 mg/kg groups had significantly greater mean body weights and body weight
      gains than did the vehicle controls. Clinical findings in rats administered
      carisoprodol in corn oil or in 0.5% methylcellulose included lethargy, ataxia,
      diarrhea, and prostration; the incidences were dose-related, and females were
      more sensitive than males to the effects of carisoprodol. In the carisoprodol in
      corn oil study, differences in hematology and clinical chemistry parameters
      occurred with no consistent patterns. The effects of carisoprodol in 0.5%
      methylcellulose on hematology and clinical chemistry parameters were not studied.
      In the corn oil study, the kidney and liver weights of male and female rats
      administered 200 mg/kg carisoprodol or greater were generally significantly
      greater than those of the vehicle controls. In the 0.5% methylcellulose study,
      liver weights were significantly greater in male rats administered 400 or 800
      mg/kg and in female rats administered 800 mg/kg carisoprodol compared to the
      vehicle controls; however, a consistent effect on the kidney weights was not
      observed. Nephropathy was observed in male rats administered 400 mg/kg
      carisoprodol or greater in corn oil; the livers of four males in the 1,600 mg/kg
      group had centrilobular hypertrophy of hepatocytes. No lesions were observed
      histopathologically in female rats administered carisoprodol in corn oil. In the
      carisoprodol in 0.5% methylcellulose study, the severity of nephropathy in males
      administered 200 mg/kg or greater was enhanced, and the incidence of nephropathy
      in female rats in the 800 mg/kg group was slightly greater than that in the
      vehicle controls. Plasma carisoprodol concentrations at the end of 13 weeks
      generally increased with increasing dose in rats administered carisoprodol in
      corn oil or in 0.5% methylcellulose. The plasma carisoprodol concentrations in
      rats administered a single gavage dose of carisoprodol in corn oil also increased
      with increasing dose. In the carisoprodol in corn oil mouse study, two females
      each in the vehicle control and 75 mg/kg groups and one female each in the 150
      and 600 mg/kg groups were accidentally killed; all males survived to the end of
      the study. One male and one female administered 1,600 mg/kg carisoprodol in 0.5%
      methylcellulose died; seven mice were accidentally killed. The mean body weights
      and body weight gains of mice administered carisoprodol in corn oil were
      generally similar to those of the vehicle controls. The final mean body weights
      and body weight gains of all groups of males and females administered
      carisoprodol in 0.5% methylcellulose were significantly less. Clinical findings
      in the carisoprodol in corn oil study included lethargy, ataxia, tremors, and
      prostration in male and female mice. Ataxia, lethargy, convulsions, and
      prostration were observed in all dosed groups of males and females administered
      carisoprodol in 0.5% methylcellulose. In the carisoprodol in corn oil study,
      liver weights were significantly greater in males administered 300 mg/kg or
      greater and in females administered 150 mg/kg or greater than in the vehicle
      controls. In the carisoprodol in corn oil study, no gross or microscopic lesions
      were considered related to carisoprodol administration. Minimal to mild
      centrilobular hypertrophy was observed in the liver of all dosed groups of males
      and in females in the 1,200 and 1,600 mg/kg groups in the carisoprodol in 0.5%
      methylcellulose study. The testis weights of males administered 1,200 mg/kg
      carisoprodol in corn oil were significantly less than those of the vehicle
      controls; the sperm motility of males in this group was also significantly less
      than that of the vehicle controls. There were no significant differences in
      vaginal cytology parameters between dosed and vehicle control females. At the end
      of the carisoprodol in corn oil study, the concentration of carisoprodol was
      above the limit of detection in the plasma of only one male mouse each in the 300
      and 1,200 mg/kg groups and in four females in the 1,200 mg/kg group. In mice
      administered a single gavage dose of carisoprodol in corn oil, plasma
      concentrations increased with increasing dose; peak plasma concentrations
      occurred at 20 to 120 minutes in males and 60 to 120 minutes in females. In the
      carisoprodol in 0.5% methylcellulose study, plasma carisoprodol concentrations of
      female, but not male, mice increased with increasing dose; peak plasma
      carisoprodol concentrations occurred at 30 minutes postdosing in all groups of
      males and females. Results of proportionality and bioavailability studies
      indicated that single gavage doses of 200 to 800 mg/kg carisoprodol in 0.5%
      methylcellulose in rats or 300 to 1,200 mg/kg in mice were dose proportional;
      absolute bioavailability values increased with increasing dose, ranging from 15%
      to 32% for rats and from 18% to 38% for mice. For rats, the bioavailability of
      carisoprodol in 0.5% methylcellulose was approximately fivefold that of
      carisoprodol in corn oil; the Cmax values of the dose in 0.5% methylcellulose
      were approximately threefold those of the dose in corn oil. For mice, no
      significant difference was observed in the bioavailability of carisoprodol
      between the vehicles; however, the Cmax values of the dose in 0.5%
      methylcellulose were 1.5 to 1.75 times those of the dose in corn oil.
      Carisoprodol was not mutagenic in any of four strains of Salmonella typhimurium,
      with or without S9 metabolic activation. It did induce mutations in L5178Y mouse
      lymphoma cells in the absence of S9; with S9, no mutagenic activity was noted in
      this assay. Results of the sister chromatid exchange test with carisoprodol in
      cultured Chinese hamster ovary cells were considered equivocal with and without
      S9. Chromosomal aberrations in cultured Chinese hamster ovary cells were clearly
      increased by carisoprodol treatment, particularly in the presence of S9. No
      significant increases in the frequency of micronucleated erythrocytes were
      observed in peripheral blood samples from male and female mice administered
      carisoprodol by gavage for 13 weeks. In conclusion, carisoprodol induced ataxia
      and prostration in rats and mice, increases in liver weights in rats and mice,
      and nephropathy in male rats. The bioavailability of carisoprodol in 5%
      methylcellulose was greater than in corn oil. The no-observed-adverse-effect
      (NOAEL) level of carisoprodol administered in corn oil or in 0.5% methylcellulose
      was determined to be 100 mg/kg, compared to the clinical dose of 20 mg/kg per day
      for adults and 5 to 7.5 mg/kg per day for children.

PMID- 11986680
TI  - NTP Toxicity Studies of Benzyltrimethylammonium Chloride (CAS No. 56-93-9)
      Administered by Gavage to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice.
AB  - Benzyltrimethylammonium chloride is widely used as a solvent for cellulose, a
      gelling inhibitor in polyester resins, a chemical intermediate, a paint
      dispersant, and an acrylic dyeing agent. It is also used in plant growth
      regulator compositions and synthetic processes. The National Institute of
      Environmental Health Sciences nominated benzyltrimethylammonium chloride for
      study due to its high production volume and the potential for occupational
      exposure, as well as the limited information on toxicity of this chemical. Male
      and female F344/N rats and B6C3F1 mice received benzyltrimethylammonium chloride
      by gavage for 16 days or 13 weeks. Animals were evaluated for hematology,
      clinical chemistry, histopathology, neurotoxicity, and reproductive toxicity.
      Genetic toxicology studies were conducted in Salmonella typhimurium and in mouse
      peripheral blood erythrocytes. In the 16-day studies, groups of five male and
      five female rats received 0, 16, 32, 63, 125, or 250 mg benzyltrimethylammonium
      chloride/kg body weight in deionized water by gavage, 5 days per week for 16
      days. Groups of five male and five female mice received 0, 63, 125, 250, 500, or
      1,000 mg/kg benzyltrimethylammonium chloride in deionized water by gavage, 5 days
      per week for 16 days. All rats in the 125 and 250 mg/kg groups, all mice in the
      250, 500, and 1,000 mg/kg groups, and one 125 mg/kg female mouse died on day 1 of
      the studies. Clinical findings observed in 125 mg/kg male and female rats
      included abnormal breathing, ataxia, lethargy (males only), nasal and eye
      discharge, and tremors. Salivation was slightly increased in male and female rats
      in the 63 mg/kg groups. Female mice in the 125 mg/kg group had a significantly
      greater absolute liver weight than that of the vehicle controls. No gross or
      microscopic changes observed in rats or mice were considered related to chemical
      administration. In the 13-week studies, groups of 10 male and 10 female rats and
      mice received benzyltrimethylammonium chloride in deionized water by gavage at
      doses of 0, 12.5, 25, 50, or 100 mg/kg, 5 days per week for 13 weeks.
      Benzyltrimethylammonium chloride generally had little effect on the body weights
      of rats or mice. Final mean body weights of dosed animals were within 8% (rats)
      or 3% (mice) of the control group body weights. The deaths of two female rats and
      one male and one female mouse administered 100 mg/kg were the result of
      pharmacologic effects on the cardiovascular system. Some cholinergic effects
      including chromodacryorrhea, lacrimation, salivation, pupillary constriction,
      altered gait, and mild tremors were observed at nonlethal doses in rats; these
      effects were accompanied by alterations in body position. No significant target
      organ toxicity was observed in dosed rats or mice. Benzyltrimethylammonium
      chloride was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535,
      with or without S9 metabolic activation enzymes. However, significant increases
      in the frequency of micronucleated normochromatic erythrocytes were found in the
      peripheral blood of male and female mice administered benzyltrimethylammonium
      chloride by gavage for 13 weeks. Based on the mortality observed in the 16-day
      and 13-week studies, rats and mice appeared to be equally sensitive to
      benzyltrimethylammonium chloride. The minimally toxic dose for rats and mice was
      estimated to be 50 mg/kg.

PMID- 11986681
TI  - NTP Toxicity Studies of 60-Hz Magnetic Fields Administered by Whole Body Exposure
      to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice.
AB  - Electric and magnetic fields are associated with the production, transmission,
      and use of electricity; thus the potential for human exposure is high. These
      electric and magnetic fields are predominantly of low frequency (60 Hz) and
      generally of low intensity. The prevailing view among physicists is that exposure
      to these low-frequency, low-intensity fields does not pose a health hazard.
      However, this view has been challenged by reports linking magnetic field exposure
      to the development of leukemia and other cancers. Because multiple epidemiologic
      studies suggested a potential for increased cancer rates with increasing
      exposure, and because of public concern, the effects of 60-Hz magnetic field
      exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body
      exposure studies. Animals were evaluated for hematology and clinical chemistry
      (rats only) parameters, pineal gland hormone concentrations, and histopathology.
      Additional studies were performed in Sprague-Dawley rats to examine teratologic
      and reproductive effects of magnetic field exposure. In the 8-week toxicity
      studies, groups of male and female F344/N rats and B6C3F1 mice were exposed for
      18.5 hours per day to 60-Hz magnetic fields at intensities of 0 (control), 0.02,
      2, and 10 gauss (G). Additional groups of rats and mice were exposed to
      intermittent 10 G fields (1 hour on/1 hour off) for 18.5 hours per day. No
      evidence of toxicity associated with exposure to magnetic fields was observed in
      rats or mice. Clinical observations provided no evidence of adverse effects
      associated with magnetic field exposure. Compared to control rats and mice, there
      were no biologically significant differences in hematology or clinical chemistry
      parameters of rats exposed to magnetic fields. No gross lesions or
      histopathologic findings in rats or mice were attributed to exposure to 60-Hz
      magnetic fields. In addition, magnetic field exposure was not associated with a
      significant reduction in serum melatonin or pineal gland melatonin concentration,
      or pineal gland activity of N-acetyltransferase in either species. One female rat
      in the 2 G exposure group died during the 8-week toxicity study from causes
      unrelated to magnetic field exposure; all other male and female rats and mice in
      the study survived until the end of the study. Final mean body weights and mean
      organ weights of a few groups of exposed animals differed from those of the
      control groups; however, no clear pattern of magnetic field effects was observed,
      and these differences are not considered to be biologically significant. For the
      teratology study, groups of 55 pregnant female Sprague-Dawley rats were exposed
      to the same magnetic fields as in the toxicity study on gestation days 6 through
      19. Fifteen pregnant females exposed to 85 mg ethylenethiourea/kg body weight
      served as positive controls. Except for the positive controls, there were no
      changes in maternal or fetal weights, nor were fetal abnormalities found. The
      number of pregnant females was significantly lower in groups exposed to magnetic
      fields than in the control group; however, all breeding in the teratology study
      was completed prior to the first day of magnetic field or sham exposure. On this
      basis, this finding is unrelated to magnetic field exposure. In addition, there
      were no differences between control and exposed groups in the number of pregnant
      females in the continuous breeding study, in which breeding took place within the
      magnetic fields. Groups of 40 breeding pairs of Sprague-Dawley rats were exposed
      to the same magnetic fields as in the toxicity study during the breeding and
      lactation of five litters in a continuous breeding study. The fifth litter was
      exposed during gestation and lactation; one male and one female from each litter
      were raised to sexual maturity receiving the same exposures as the parents; rats
      were mated to nonsibling rats and allowed to deliver the third-generation
      offspring. The results of the continuous breeding study demonstrated no effects
      of magnetic field exposure on reproductive performance in either male or female
      rats.

PMID- 11986682
TI  - NTP Technical Report on the Toxicity Studies of 3,3',4,4'-Tetrachloroazobenzene
      (CAS No. 14047-09-7) Administered by Gavage to F344/N Rats and B6C3F1 Mice.
AB  - 3,3',4,4'-Tetrachloroazobenzene is not commercially manufactured but is formed as
      an unwanted byproduct in the manufacture of 3,4-dichloroaniline and its
      herbicidal derivatives Propanil(R), Linuron(R), and Diuron(R). In addition,
      environmental contamination by 3,3',4,4'-tetrachloroazobenzene occurs from the
      degradation of chloranilide herbicides and the photolysis and biolysis of 3,4
      dichloroaniline. 3,3',4,4'-Tetrachloroazobenzene was nominated by the United
      States Environmental Protection Agency for toxicity testing based on concerns
      over the potential for human exposure, the structural resemblance to 2,3,7,8
      tetrachlorodibenzo-p-dioxin, and the reported dioxin-like effects of 3,3',4,4'
      tetrachloroazobenzene. The toxicity of 3,3',4,4'- tetrachloroazobenzene was
      evaluated in 16-day and 13-week gavage studies in male and female F344/N rats and
      B6C3F1 mice. In addition to histopathology, evaluations included hematology (rats
      only), clinical chemistry, thyroid hormone analyses (rats only), cytochrome
      P(450)1A immunohistochemical staining in the liver (rats only), and assessments
      of male reproductive endpoints and estrous cycle length. Genetic toxicology
      studies included mutagenicity tests in Salmonella typhimurium and the
      determination of micronuclei in mouse bone marrow and peripheral blood
      erythrocytes. In the 16-day studies, groups of five male and five female rats
      received 3,3',4,4'-Tetrachloroazobenzene in corn oil by gavage 5 days a week at
      doses of 0, 12.5, 32, 80, 200, or 500 mg per kg body weight. Groups of five male
      and five female mice received 3,3',4,4'-Tetrachloroazobenzene in corn oil by
      gavage 5 days a week at doses of 0, 1, 3.2, 10, 32, or 100 mg/kg. Major effects
      included increases in liver, lung, and spleen weights of rats and liver and heart
      weights of mice and decreases in thymus weights of rats and mice. No effects were
      found on survival or mean body weight gains of rats or mice. Incidences of
      hematopoietic cell proliferation in the spleen were increased in all groups of
      dosed male rats, in female rats that received 32 mg/kg or greater, and in 100
      mg/kg male and female mice. Renal tubule hyaline droplet accumulation in the
      cytoplasm of renal cortical epithelial cells and chronic nephropathy were
      observed microscopically in male rats in the 80, 200, and 500 mg/kg groups.
      Female mice in the 100 mg/kg group had atrophy of the thymus. In the 13-week
      studies, groups of 10 male and 10 female rats and mice received 3,3',4,4'
      Tetrachloroazobenzene in corn oil by gavage 5 days a week at doses of 0, 0.1, 1,
      3, 10, or 30 mg/kg. In the 13-week rat study, the major effects included a
      decrease in the mean body weight gain of 30 mg/kg females and final mean body
      weights of 30 mg/kg males and females, decreased thymus weights of males and
      females in the 10 and 30 mg/kg groups accompanied by thymic atrophy observed
      microscopically, increased incidences of hematopoietic cell proliferation in the
      spleen in 10 and 30 mg/kg males and females, a responsive anemia in 10 and 30
      mg/kg males and females at week 13, and decreased platelet counts in 10 and 30
      mg/kg males and females on day 21 and at week 13. Spleen weights were increased
      in 10 and 30 mg/kg males and females. Liver weights were increased in males that
      received 1 mg/kg or greater and in 10 and 30 mg/kg females. Furthermore, hepatic
      cytochrome P(450)1A staining presence and intensity were increased in 30 mg/kg
      males and females. Sharp decreases in circulating thyroxine concentrations were
      observed in males and females at all doses. In spite of this sharp decrease,
      thyroid-stimulating hormone concentrations were marginally increased. Incidences
      of hyperplasia of the forestomach were increased in males administered 3 mg/kg or
      greater and females administered 30 mg/kg. In the 13-week mouse study, the major
      effects included increases in liver and spleen weights of 10 and 30 mg/kg males
      and females and increased incidences of hyperplasia of the forestomach in males
      and females that received 1 mg/kg or greater. Furthermore, a decrease in thymus
      weight of 30 mg/kg males, an increase in centrilobular hypertrophy of hepatocytes
      in males that received 3 mg/kg or greater, and an increase in the incidences of
      hematopoietic cell proliferation in the spleen in males that received 3 mg/kg or
      greater were observed. A significant decrease in epididymal spermatozoal
      concentration was observed in 3 and 30 mg/kg males. 3,3',4,4'
      Tetrachloroazobenzene was mutagenic in S. typhimurium strain TA97 in the presence
      of rat liver S9 activation enzymes; no mutagenic activity was detected in strain
      TA98, TA100, TA1535, or TA1537 with or without S9. In vivo, the frequency of
      micronucleated erythrocytes was significantly increased in peripheral blood
      samples from male and female mice given 3,3',4,4'-Tetrachloroazobenzene by gavage
      for 13 weeks. However, results of a 3-day exposure of up to 200 mg/kg by
      intraperitoneal injection did not demonstrate induction of micronuclei in bone
      marrow erythrocytes of male mice. In summary, 3,3',4,4'-Tetrachloroazobenzene
      caused typical dioxin-like effects, such as thymic atrophy, an increase in liver
      weights, induction of hepatic cytochrome P(450)1A, and decreased mean body weight
      gains. Furthermore, in the 13-week studies, a sharp decrease in circulating
      thyroxine concentrations was observed even at the lowest dose (0.1 mg/kg) tested
      in rats. Other effects included a decrease in epididymal spermatozoal
      concentration in mice, major effects on the hematopoietic system, and increased
      incidences of hyperplasia of the forestomach in 3 and 30 mg/kg males and 30 mg/kg
      females. A no-observable-adverse-effect-level (NOAEL) was not reached in rats.
      The NOAEL in mice was 0.1 mg/kg. Comparison of various dioxin-like effects in
      these studies with those reported in the literature indicate that 3,3',4,4'
      Tetrachloroazobenzene is six to two orders of magnitude less potent than 2,3,7,8
      tetrachlorodibenzo-p-dioxin.

PMID- 11986683
TI  - NTP Technical Report on the Toxicity Studies of 3,3',4,4'-Tetrachloroazoxybenzene
      (CAS No. 21232-47-3) Administered by Gavage to F344/N Rats and B6C3F1 Mice.
AB  - 3,3',4,4'-Tetrachloroazoxybenzene is not commercially manufactured but is present
      as a contaminant of 3,4-dichloroaniline and its herbicidal derivative Diuron(R).
      In addition, environmental contamination occurs when 3,3',4,4'
      tetrachloroazoxybenzene is formed by the photolysis and biolysis of 3,4
      dichloroaniline. 3,3',4,4'-Tetrachloroazoxybenzene was nominated by the United
      States Environmental Protection Agency for toxicity testing based on concerns
      over the potential for human exposure, the structural resemblance to 2,3,7,8
      tetrachlorodibenzo-p-dioxin, and the reported dioxin-like effects of 3,3',4,4'
      tetrachloroazoxybenzene. The toxicity of 3,3',4,4'-tetrachloroazoxybenzene was
      evaluated in 16-day and 13-week gavage studies in male and female F344/N rats and
      B6C3F1 mice. In addition to histopathology, evaluations included hematology (rats
      only), clinical chemistry, thyroid hormone analyses (rats only), hepatic cell
      proliferation (rats only), cytochrome P(450)1A immunohistological staining in the
      liver (rats only), and assessments of male reproductive endpoints and estrous
      cycle length. Additional genetic toxicology studies included mutagenicity tests
      in Salmonella typhimurium and the determination of micronuclei in mouse bone
      marrow and peripheral blood erythrocytes. In the 16-day studies, groups of five
      male and five female rats received 3,3',4,4'-tetrachloroazoxybenzene in corn oil
      by gavage at doses of 0, 12.5, 32, 80, 200, or 500 mg per kg body weight, 5 days
      a week. Groups of five male and five female mice received 0, 1, 3.2, 10, 32, or
      100 mg/kg in corn oil by gavage, 5 days a week. Major effects in rats included
      increases in liver and lung weights, and decreases in mean body weights and body
      weight gains, heart weights, and thymus weights. Effects in mice included
      increases in liver weights and decreases in thymus weights. No effects on
      survival were observed. Treatment-related lesions included cytoplasmic alteration
      of hepatocytes, splenic hematopoietic cell proliferation, thymic atrophy, and
      nephropathy in rats and thymic atrophy, splenic hematopoietic cell proliferation,
      and hepatic foci of inflammation and necrosis in mice. In the 13-week studies,
      groups of 10 male and 10 female rats and mice received 3,3',4,4'-
      tetrachloroazoxybenzene in corn oil by gavage at doses of 0, 0.1, 1, 3, 10, or 30
      mg/kg, 5 days a week. In the 13-week rat study, all males and seven females in
      the 30 mg/kg groups died. Decreases in final mean body weights and body weight
      gains were observed in 3 and 10 mg/kg males and 10 and 30 mg/kg females.
      Decreased thymus weights, accompanied by thymic atrophy observed microscopically,
      were observed at doses of 1 mg/kg or greater in males and females. Increased
      liver weights were observed in males and females administered 1 mg/kg or greater,
      and hepatic cytochrome P(450)1A staining was increased in 1 and 3 mg/kg males and
      3, 10, and 30 mg/kg females. In addition, a responsive anemia and decreases in
      platelet counts were observed in dosed male and female rats. A marked decrease in
      circulating thyroxine concentrations was observed in dosed males and females. In
      spite of this sharp decrease, thyroid-stimulating hormone concentrations were
      marginally increased. A decrease in epididymal spermatozoal motility was observed
      in all dosed groups tested. In 10 mg/kg females, the estrous cycle length was
      increased. Major effects included increased incidences of hyperplasia of the
      forestomach in 3, 10, and 30 mg/kg males and 10 and 30 mg/kg females. Increased
      incidences of centrilobular degeneration and hematopoietic cell proliferation
      were observed in the liver of dosed males and females. Furthermore, chronic
      active inflammation of the lung vasculature and hematopoietic cell proliferation
      in the spleen were observed in dosed males and females. The increased severities
      of cardiomyopathy and nephropathy in males and the incidences of cardiomyopathy
      and nephropathy and severity of cardiomyopathy in females were 3,3',4,4'
      tetrachloroazoxybenzene related. In the 13-week mouse study, the major effects
      included increases in liver weights in males administered 3 mg/kg or greater and
      females administered 1 mg/kg or greater. Hyperplasia of the forestomach and
      dilatation of hair follicles were observed in 10 and 30 mg/kg males and 30 mg/kg
      females. Furthermore, thymus weights were decreased in males administered 3 mg/kg
      or greater and in 10 and 30 mg/kg females. Increased incidences of centrilobular
      hypertrophy of hepatocytes were observed in 10 and 30 mg/kg males and females.
      Increased incidences of hematopoietic cell proliferation in the spleen were
      observed in 30 mg/kg males and in 10 and 30 mg/kg females. Increases in the
      incidences of thymocyte necrosis were observed in 10 mg/kg males and in 10 and 30
      mg/kg females. The incidences of splenic pigmentation were increased in all dosed
      groups of males, and the severity of pigmentation increased with increasing dose
      in males and females. 3,3',4,4'-Tetrachloroazoxybenzene was not mutagenic in S.
      typhimurium strain TA97, TA98, TA100, or TA1535 with or without induced S9
      metabolic activation enzymes. It did not induce significant increases in
      micronucleated erythrocytes in a three-exposure male mouse bone marrow
      micronucleus test up to dose levels of 200 mg/kg, but results of a 13-week
      peripheral blood micronucleus test conducted in male and female mice were
      positive. In summary, 3,3',4,4'-tetrachloroazoxybenzene caused typical dioxin
      like effects, including thymic atrophy, increased liver weights, induction of
      hepatic cytochrome P(450)1A, and decreased mean body weight gains. Furthermore, a
      marked decrease in circulating thyroxine concentrations was observed in male and
      female rats, even at the lowest dose (0.1 mg/kg) in female rats. A decrease in
      epididymal sperm motility was observed at all doses in rats. Effects on the
      hematopoietic system occurred at doses including and lower than those that caused
      histopathologic alterations in the liver. A no-observable-adverse-effect-level
      (NOAEL) was not reached in rats. In male and female mice, the NOAEL was 1 and 0.1
      mg/kg, respectively. Furthermore, treatment-related effects included increased
      incidences of hyperplasia of the forestomach epithelium in rats and mice, chronic
      active inflammation of the vasculature of the lung in rats, increased incidences
      and/or severities of cardiomyopathy and nephropathy in rats, and dilatation of
      the hair follicles in mice. Comparison of various dioxin-like effects in these
      studies with those reported in the literature indicate that 3,3',4,4'-
      tetrachloroazoxybenzene is six to two orders of magnitude less potent than
      2,3,7,8-tetrachlorodibenzo-p-dioxin.

PMID- 11986684
TI  - [Pathological and virological studies of the liver tissues from the patients with
      sporadic hepatitis E].
AB  - OBJECTIVE: To study the pathological feature, viral distribution and replication
      in the liver tissue of sporadic hepatitis E(HE), and to explore the mechanism of
      the liver injury induced by hepatitis E virus(HEV). METHODS: The total bioptic
      liver tissues (n=54) were obtained from the patients with sporadic hepatitis E,
      including the clinical acute stage (n=20), the convalescent stage (n=16), and the
      chronic hepatitis B (CHB) overlapped with HEV infection recently (n=18). The
      pathological changes in the liver tissues were observed under the light and the
      electron microscope. HEV RNA was detected by in situ hybridization, and Kupffer
      cells were marked with immunohistochemistry. RESULTS: The HE liver tissues showed
      the pathological features in the clinical acute stage, presenting frequently with
      feathery degeneration of hepatocytes (100%), cholangiolar cholestasis (75.0%),
      and double nuclei and multinuclei hepatocytes (65.0%). The apoptotic body of
      hepatocyte was larger and irregular, and the proliferation of Kupffer cells was
      prominent. HEV RNA was distributed in hepatocyte cytoplasm near the nuclei. The
      positive rate of HEV RNA in acute stage was evidently higher than that in
      convalescent stage (100% vs 12.5%,P < 0.001), and the HEV RNA positive
      hepatocytes and the viral copies in acute stage were also more than in
      convalescent stage, in which the liver tissues were becoming normal. The liver
      tissue changes of the CBH overlapped with HEV infection were more severe compared
      with the single CHB. CONCLUSIONS: Sporadic HE had histopathological
      characteristics. HEV infection and replication in hepatocytes occurred mainly
      during clinical acute stage and regressed in convalescent stage, which suggested
      sporadic acute HE may have a good result. The immune-mediated liver injury by
      lymphocytes might be a main pathogenesis of HE,but the liver injury induced
      directly by HEV might not be excluded.

PMID- 11986685
TI  - [Chromosome aberration and carcinogenicity of CHO dhfr- cells transformed by
      plasmid containing S+ and Pre S1 of fusion gene of hepatitis B virus].
AB  - OBJECTIVE: To investigate the chromosome aberrations and carcinogenicity of CHO
      dhfr- cell induced by integration of plasmid containing S+ and Pre S1 fusion gene
      of hepatitis B surface antigen (HBsAg). METHODS: The plasmid pCHBSS1G was
      constructed with S+ Pre S1 of HBsAg. CHO-dhfr- cells were transformed with this
      recombinant plasmid DNA and CHO cells lines with integrated DNA were cloned and
      named GdSS118. The GdSS1 18 cell lines secreting the S+ Pre S1 fusion protein of
      HBsAg at high level were developed by screening in increased concentration of MTX
      and MSX in cultured media. To make sample of cells chromosome, the cells
      integrated DNA were subcutaneously injected into nude mouse. RESULTS: The CHO
      dhfr- cell lines integrated with S and Pre S1 fusion protein of HBsAg were
      developed and named GdSS1-18 cell lines. The frequencies and type of chromosome
      aberrations of the GdSS1-18 cell lines with different passage generations were
      11%, 56% and 29%, respectively, while that of the control CHO-dhfr- cell lines
      was 6%. There was no change in the mode of chromosomes, both cell lines having 20
      chromosome s. Both cell lines were non-oncogenic in nude mouse. CONCLUSIONS: The
      chromosome aberration of CHO-dhfr- cells with integrated DNA were obviously
      higher than that of the original CHO-dhfr- cells without integrated DNA. Both
      cell lines were non oncogenic in nude mouse.

PMID- 11986686
TI  - [Prevalence of mutants in the    determinant region of hepatitis B surface
      antigen among Chinese carriers after receiving only active postexposure
      immunoprophylaxis].
AB  - OBJECTIVE: To determine the frequency of hepatitis B surface antigen (HBsAg)
      mutations in the alpha determinant region among children who developed chronic
      hepatitis B virus (HBV) infection after receiving only active postexposure
      immunoprophylaxis. METHODS: HBsAg mutations were determined by PCR-directed
      nucleotide sequencing and sequence-specific solid-phase PCR analysis(SS-SPPCR)
      for 97 Chinese carrier cases after hepatitis B vaccination, for 88 children born
      aged women controls, and for 95 population based children controls. RESULTS:
      Prevalence of amino acid substitutions as detected by direct sequencing among
      carrier cases, women controls, and children controls were 30.9%, 10.2%, and 5.3%,
      respectively. The most frequent amino acid substitutions observed were at
      residues 145, 126, and 133. However, there was no difference in the prevalence of
      145 and 126 amino acid mutants as detected by a sensitive SS-SPPCR method between
      carrier cases and controls. The prevalence of 145 Arg and 145 Ala mutants that
      were detected by SS-SPPCR was 39.2%, 33.0% and 32.6% among carrier cases, women
      controls, and children controls, respectively. The total odds ratio was 5.41 for
      mutants detected by direct sequencing. Odds ratio were 34.55 and 33.39 among adw2
      subtype and genotype B subjects for mutants detected by direct sequencing,
      respectively. CONCLUSIONS: The results show that hepatitis B virus mutants in the
      determinant are fairly consistent observed but without immune selective
      pressures; HBV variant strains may pre-existent as minor quasispecies. The
      prevalence of mutants is related to HBV subtypes and genotypes.

PMID- 11986687
TI  - [Screening and characterization of human phage antibody to hepatitis virus C NS5A
      antigen].
AB  - OBJECTIVE: To screen and characterize human phage antibody against hepatitis C
      virus (HCV)NS5A antigen. METHODS: The recombinant phages were panned by
      recombinant HCV NS5A antigen which was coated in a microtiter plate; after five
      rounds of biopanning, 35 clones were obtained and demonstrated specific to NS5A
      antigen. The specific binding capacity of the ScFv antibody to HCV NS5A antigen
      was determined by ELISA. RESULTS: HCV NS5A phage antibody had a specific
      combination capacity with hepatitis C virus NS5A antigen. The DNA sequence data
      showed that the ScFv gene was composed of 789 bp and codes for a peptide of 262
      amino acid residues. CONCLUSIONS: Human single chain antibody to hepatitis C
      virus NS5A antigen has been identified by means of the phage display technology.

PMID- 11986688
TI  - [Analysis of the nucleotide sequence for C and NS5 regions and the genotype of
      HCV isolate in Shandong Province].
AB  - OBJECTIVE: To study the genotype of HCV epidemic strains in Shandong Province.
      METHODS: HCV fragments of C(432 bp) and NS5(319 bp) regions were amplified by RT
      nested PCR. The fragments were cloned to T vector and sequenced by
      dideoxynucleotide chain termination reaction. RESULTS: Three of all 4 strains in
      C region were 1b genotype, and 1 was 2a. All of 10 strains of NS5 region were 1b
      genotype. No other genotype was found in this region. The homology of nucleotide
      sequence was over 90% compared with that of more than 50 strains in Gen Bank.
      CONCLUSIONS: The major genotype of HCV epidemic strains in Shandong Province is
      1b. The 2a genotype is also found in this area.

PMID- 11986689
TI  - [The recombinant vaccinia viruses expressing HPV type 16 wild or mutant E7
      protein elicit immunity against tumor cells in mice].
AB  - OBJECTIVE: To select mutants of HPV 16 E7 suitable for vaccine development.
      METHODS: Several recombinant vaccinia viruses (VwE7, VmE7-1, and VmE7-2)
      expressing wild E7 or its mutants, ME7-1 (24G26G) and ME7-2 (24G26G91G)
      respectively, were employed to study their antigenicity and anti tumor activity.
      RESULTS: Both VmE7-1 and VwE7 could elicit cytotoxic T lymphocytes (CTL)and
      protect mice against tumor cells challenge, but VmE7-2 could not induce the
      immune reactions compared with VmE7-1 and VwE7. CONCLUSIONS: It suggested that
      ME7-1 could be used to develop a therapeutic vaccine for cervical cancer.

PMID- 11986690
TI  - [Examination and evaluation of lipopolysaccharide binding protein in serum of
      patients with chronic hepatitis, severe hepatitis].
AB  - OBJECTIVE: To observe the variability of lipopolysaccharide binding protein (LBP)
      in patients with chronic hepatitis and severe hepatitis. METHODS: Using ELISA the
      authors detected the serum LBP of 71 patients including 16 with chronic
      hepatitis, 15 with post hepatitis cirrhosis, 12 with severe hepatitis and 17
      healthy controls. RESULTS: The serum LBP of chronic liver disease group was 35
      166.25 micrograms/L, which was higher than that of healthy control group (18
      590.00 micrograms/L). The serum LBP of chronic hepatitis and cirrhosis patients
      was higher than that of severe hepatitis cases. These differences were
      significant. The serum LBP had positive correlation with prothrombin activity
      (PTA) (r =0.395 8,P <0.01), while it had no significant correlation with serum
      ALT and total bilirubin levels (r =0.164 5,0.189 4, respectively, P <0.05).
      CONCLUSIONS: Serum LBP could be used as an index for predicting liver function
      compensation.

PMID- 11986691
TI  - [Regulatory effect of Bcl-2 on the cortical neurons of primary cultured mice with
      HSV-1 infection].
AB  - OBJECTIVE: To study the effect of Bcl-2 on the cortical neurons of primary
      cultured mice with HSV-1 infection. METHODS: Analysis of the expression of Bcl-2
      on the cortical neurons of primary cultured fetal mice in vitro infected with HSV
      1 for 11 hours or exposed to sorbitol for 5 hours was made by flow cytometry and
      Western blotting. RESULTS: The Bcl-2 of the cultured neurons undergoing HSV-1
      infection expressed upregulating compared with the mock untreated neurons. The
      Bcl-2 protein of HSV-1 infected and exposed to sorbitol neurons expressed
      upregulating compared with the control group. The Bcl-2 protein of the primary
      cultured 3 day cells expressed higher than that of the primary cultured 7 day
      cells. The higher neurovirulence, the higher expression of Bcl-2. CONCLUSIONS:
      Bcl-2 might protect the primary cultured cortical neurons of fetal mice from
      apoptosis where infected with HSV-1, and thereby the lifespan of host cells may
      be prolonged.

PMID- 11986692
TI  - [A discussion on diagnosis and typing of viral hepatitis].
AB  - OBJECTIVE: To bring forward a suggestion about clinical diagnostic standard and
      clinical typing for chronic and severe hepatitis. METHODS: To make a
      comprehensive study on clinical features and pathology of 895 cases of severe and
      chronic hepatitis, liver cirrhosis after hepatitis based on the viral prevention
      and control plan laid down in 1995. RESULTS: The chronic hepatitis can still be
      divided into mild, moderate and severe types clinically, but the PTA should be
      changed for normol-71, 70-61, 60-51, the A/G value for normal, 1.5-1.3, 1.2-1.0
      respectively. ALT, BIL, alpha-globulin are kept unchanged. The albumin value can
      be cut out from the reference indexes of clinical typing for chronic hepatitis.
      Acute severe hepatitis can be divided into early stage (taking edema as the main
      type) and late stage (taking necrosis as the main type); subacute severe
      hepatitis can be divided into ascite type, coma type and mixed type; if those
      lacking of coma and ascite with PTA about 60%. 50% can be treated as earlier
      stage. Subacute and chronic severe hepatitis still can be divided into early,
      middle and late stages. The disease course of subacute severe hepatitis may
      prolong to six months. Chronic severe hepatitis can be divided into type B
      (typical chronic hepatitis type) type C (liver cirrhosis type) and type c (acute
      liver failure type developed from chronic hepatitis and viral carriers).
      CONCLUSIONS: The original procedure of 1995 are feasible on the whole.

PMID- 11986693
TI  - [The predomination of rotavirus G3 serotype among children with diarrhea in
      Lulong County in 1998].
AB  - OBJECTIVE: To investigate the epidemiology of rotavirus diarrhea among children
      in rural population. METHODS: 120 stool specimens collected from children with
      diarrhea during the winter of 1998 in Lulong County, Hebei Province were examined
      for rotavirus by PAGE and ELISA and for serotype by ELISA and PCR. RESULTS:
      Rotavirus was detected in children aged between 2-24 months. The positive rate of
      rotavirus was 39.2% and the ratio of male to female was 1-1.47. All rotavirus RNA
      profiles were long pattern. The distribution of rotavirus serotypes was type
      3(61.7%), followed by type 1(36.2%), and type 4(6.4%). CONCLUSIONS: The
      epidemiology of rotavirus diarrhea during 1998 rotavirus season in Lulong County
      was similar to that of other regions in China, but rotavirus serotype G3 was a
      prevalent strain in Lulong County, which was uncommon and different from the
      predominant G1 in other places throughout China.

PMID- 11986694
TI  - [Influence of a triplex superimposed treatment on HBV replication and mutation
      during treating chronic hepatitis B].
AB  - OBJECTIVE: To observe and evaluate the influence of a new antiviral treatment
      scheme on HBV replication and mutation during treating chronic hepatitis B.
      METHODS: In the test group, lamivudine, IFN alpha-2b, Astragalus membranaceus
      were chosen as a triplex superimposed treatment scheme for treating the patients
      who were on the state of HBV high replication and involved in the clinical
      condition of chronic hepatitis B. The control group was treated with lamivudine
      alone. The observed parameters percentage of patients in whom HBV DNA became
      undetectable (serum HBV DNA<1.6 ng/L), HBeAg/anti-HBe seroconversion rate; HBV
      DNA serum level; HBV YMDD mutation rate and pre-C region mutation rate. RESULTS:
      Compared with that of the control group, HBV DNA undetectable rate of the test
      group increased markedly at weeks 12, 36, 48(P <0.05), HBeAg negative rate of the
      group increased markedly at week 36, 48(P <0.05), while anti-HBe positive rate
      increased only at week 48 (31.58 vs.19.23%, P <0.05). After 4 weeks of treatment,
      HBV DNA serum level of both the test group and the control group reduced very
      remarkably (P <0.01), and at week 48, reduced more significantly (P <0.001).
      Compared with the control group, HBV DNA serum level of the test group reduced
      notably at week 12 (P <0.05) and very notable at week 36 and 48(P <0.01). At week
      12, the pre-C region mutation occurred in the test group, and at week 24, 36,48,
      the pre-C region and YMDD mutations occurred in both the test group and the
      control group. CONCLUSIONS: As to anti-viral treatment of chronic hepatitis B,
      the triplex superimposed treatment had better efficacy than lamivudine alone.

PMID- 11986695
TI  - [Long-term efficacy of vaccination against hepatitis B in newborns: 13 years'
      follow-up].
AB  - OBJECTIVE: To evaluate long-term efficacy of hepatitis B vaccination in newborns.
      METHODS: In the past 13 years we followed up the children who had been immunized
      with hepatitis B vaccine at birth in 1986 every other year. At each follow-up
      visit, every child was tested for HBsAg, anti-HBs and anti-HBc. RESULTS: HBsAg
      positive rate of these birth cohort was low (range between 0.46% and 0.98%)
      during 13 years' follow-up. Long-term efficacy of the vaccination in preventing
      HBsAg carriage was confirmed. CONCLUSIONS: Thirteen years later no booster was
      after needed.

PMID- 11986696
TI  - [Identification of the genome of a picornavirus isolate using Random-PCR].
AB  - OBJECTIVE: To identify the genome of an enterovirus isolate (XJ90). METHODS: The
      double-stranded cDNA of isolated virus was synthesized with anchored-random
      primer and was amplified with anchor primer; the PCR products were cloned into
      pGEM-T vector for sequencing and analysis. RESULTS: Analysis on agarose gel
      electrophoresis of the Random-PCR products showed a typical smear; 11 randomly
      selected clones were all homologous to the members of enteroviruses and the
      homology rate over 80%; the 11 clones were distributed evenly along the whole
      genome and they assembled 4 contigs totally 2 261 bp long which covered 30% of
      the genome. The homology of the fourth contig and coxsackie virus B6 was 97.3% at
      amino acids level. The virus gene was specifically amplified with primers derived
      from the sequenced clones. CONCLUSIONS: The picornavirus isolate XJ90 is a member
      of enteroviruses.

PMID- 11986697
TI  - [Discovery of natural variant strain of HIV1 in env gene C2-V3 encoded PND of
      membrane protein].
AB  - OBJECTIVE: To sequence and analyze the env gene C2-V3 region of proviral genome
      from a HIV1 isolate(WWBH7) which was obtained from Huadong Area in China.
      METHODS: The env gene C2-V3 DNA fragment was amplified by nested-primer PCR with
      genome DNA of eripheral blood mononuclear cells from a confirmed HIV1 infected
      individual as a template. The amplified DNA fragment was inserted into pGEM-T
      vector. The recombinant plasmid was confirmed by restriction enzyme analysis. The
      inserted DNA fragment was sequenced by ABI737 autosequencer and analyzed by
      PROSIS software. RESULTS: The HIV1 strain was the derivatives of HIV1 B subtype.
      But there was mutation of 192 bp fragment repeated insertion at env C2-V3 region
      of the HIV1 strain compared with standard HIV1 B subtype such as SF2 strain. The
      mutation brought about a double V3 region in gene encoded PND (principal
      neutralizing domains). The DNA sequence was registered in GenBank (AF220245).
      CONCLUSIONS: This was a natural mutated variant strain of HIV1 whose genome
      showed a 192 bp repeated insertion at C2-V3 region of env gene encoded PND of
      membrane protein.

PMID- 11986698
TI  - [Detection of HPV16 E6 gene in cervical tissues by quantitative polymerase chain
      reaction].
AB  - OBJECTIVE: To study the relationship between the quantities of HPV16 E6 gene in
      cervical tissues and the course of cervical disease. METHODS: The number of
      copies of HPV16 E6 gene was detected by competitive PCR in 44 positive samples
      including 20 cases of chronic cervicitis, 6 cases of cervical dysplasia and 18
      cases of cervical cancer. RESULTS: The mean copies of HPV16 E6 gene in chronic
      cervicitis, cervical dysplasia and cervical cancer were 6.16, 5.33, and 6.45
      copies in each microgram of cervical tissue respectively. The quantities of HPV16
      E6 gene were not significantly different between cervical dysplasia and chronic
      cervicitis (P<0.01). CONCLUSIONS: This study underscores the importance of the
      relationship between the quantities of HPV16 E6 gene and the course of cervical
      disease. It also suggests that quantification of HPV16 E6 gene may be useful as a
      prognostic tool to identify women who are at increased risk of developing
      cervical cancer.

PMID- 11986699
TI  - [Isolation of HIV-1 from infected individuals in Fujian Province].
AB  - OBJECTIVE: To isolate the virus from HIV-1 infected individuals. METHODS: Blood
      specimens were collected from 10 HIV-1 infected persons in Fujian Province.
      Peripheral blood mononuclear cells (PBMCs) were separated from the heparinized
      blood. Each sample was cocultured with fresh normal PBMCs to isolate HIV-1.
      Supernatant of the cocultures was tested by using HIV-1 P24 antigen Kit. RESULTS:
      Of the 10 specimens, 9 showed positive for the P24. 4 of 9 isolated infected MT4
      cells, and cell syncytias could be seen. Three isolates showed transient
      infection of MT4, which probably belong to slow/low virus. Only one isolate could
      infect MT4 successively, which had been passed for 15 generations without
      significantly changed viral titer; it is believed to be a rapid/high replication
      virus. CONCLUSIONS: HIV-1 virus was successfully isolated.

PMID- 11986700
TI  - [Detection of HPV DNA and its relationship with peripheral T cell subsets in
      patients with condyloma acuminata].
AB  - OBJECTIVE: To study the relationship between presence of HPV DNA related sequence
      and cellular-immune responses in patients with condyloma acuminata (CA). METHODS:
      HPV DNA related sequences in biopsy material of 30 CA patients were determined by
      using Southern blot hybridization, and typed according to the restricted fragment
      length polymorphism (RFLP) analysis. At the same time, the T-cell subpopulations
      in peripheral blood of 30 patient with CA were also measured by using anti-CD3,
      CD4, CD8 monoclonal antibody labeled SERC direct rosette assay. RESULTS: HPV DNA
      positive results were revealed in 19 of 30 patients with CA(63.3%). Among them, 3
      cases possessed HPV 6 DNA homologous sequence (15.8%), 15 had HPV 11 DNA
      homologous sequence(78.9%), and only one case had a sequence homologous to HPV 16
      DNA(5.2%). The percentages of CD3 and CD4 cells were significantly lower (P<
      0.01) in CA patients than those in controls. However the percentage of CD8 cell
      was strikingly higher (P< 0.001) in CA patients than that in controls.
      Consequently the CD4/CD8 ratio was noticeably lower (P<0.001) in patients with CA
      than that in controls. The decrease of CD3 cell and the lowering of C D4/CD8
      ratio were closely related to the positivity of HPV DNA homologous sequence (P
      =0.008 02, P=0.004 17). Conclusion The presence of HPV DNA in the patients with
      CA results in inhibitory effects on a series of cellular-immune responses, which
      may play an important role in the pathogenesis of CA.

PMID- 11986701
TI  - [Cloning and nucleotide sequencing of full length L segment cDNA of Hantavirus
      strain A9].
AB  - OBJECTIVE: Cloning and nucleotide sequencing of full length cDNA sequence of L
      segment of Hantavirus strain A9. METHODS: The L segment cDNA of Hantavirus strain
      A9 was amplified by RT-PCR. PCR products were cloned and sequenced. Full length
      cDNA clone of the L segment was obtained by subcloning. RESULTS: The L segment of
      strain A9 was 6 533 nucleotides in length and encoded a putative L polymerase
      that was 2 151 amino acids in length. Analysis of nucleotide and deduced amino
      acid sequences of the L segment of strain A9 showed a close relationship with the
      other Hantaviruses most notably the 76-118, Cl-1 and Cl-2 strains, with which
      they shared a 83.8% nucleotide identity. More distant similarity could also be
      seen with other Hantaviruses. Sequence comparison performed among the RNA
      dependent RNA polymerases of 27 negative stranded RNA viruses revealed that the
      same existence of six conserved regions and several strictly conserved residues
      located at the deduced amino acid sequence of A9 L segment. CONCLUSIONS: The
      nucleotide sequence of L segment of strain A9 was similar to other Hantavirus L
      segments. Deduced amino acid sequence of A9 L segment shares 6 conserved regions
      with other RNA virus RNA polymerase. The conserved residues in these polymerases
      and their possible functions in light of the available structural information
      have been discussed.

PMID- 11986702
TI  - [Detection of cytomegalovirus infection in recipients of renal transplantation].
AB  - OBJECTIVE: To investigate infection of cytomegalovirus (CMV) in recipients of
      renal transplantation (RT). METHODS: 167 recipients of RT were screened for the
      occurrence of CMV infection by using ELISA to test anti-CMV IgG, IgM from serum
      samples, using immunohistochemistry method to test CMV antigen expression and
      nest PCR to amplify CMV DNA from blood samples. RESULTS: Of these samples, 165
      and 3 came out positive of IgG and IgM with the positive rate being 98.8% and
      1.8% respectively. 79 samples resulted in antigen expression (47.3%) with the
      average antigen index being (3.2, 3.1)/5, 104 WBC. Besides, 85 samples were found
      to be positive by nest-PCR with the positive rate being 50.9%. CONCLUSIONS: The
      results indicate that the infection of RT so the detection CMV is common in
      recipients of RT. So detection of CMV-antibody, CMV antigen and CMV DNA after
      renal transplantation is very important in early diagnosis of CMV infection.

PMID- 11986703
TI  - [Expression and drug resistance of human MGMT gene in hemopoietic cells mediated
      by bicistronic retroviral vector].
AB  - OBJECTIVE: To increase myeloid progenitors resistance to chemotherapy and prevent
      myelosuppression caused by alkylating agents. METHODS: Total cellular RNA was
      extracted from human liver and cDNA was synthesized by superscript reverse
      transcriptase, a polymerase chain reaction(PCR) was conducted. We obtained a full
      length cDNA fragment encoding human alkyguarine-DNA-alhyltransferase(MGMT). The
      PCR product was cloned into pGEMT-T vector and further subcloned into G1Na
      retrovirus expression vector. Then the recombinant plasmid was transduced into
      the packaging cell lines GP+E86 and PA317 by lipofect AMINE. RESULTS: By using
      the medium containing BCNU for cloning selection and ping-ponging supernatant
      infection between ecotropic produced clone and amphotropic producer clone, we
      obtained high titer amphotropic PA317 producer clone with the highest titer up to
      8.6-10 CFU/ml. Human hematopoietic cells were infected repeatedly with this high
      titer virus under stimulation of hemopoietic growth factors IL-3, IL-6 and SCF.
      PCR, RT-PCR, Southern blot, Western blot and MTT analyses showed that MGMT gene
      has integrated into the genomic DNA of human hemopoietic cells and expressed
      efficiently. CONCLUSIONS: This study provides a foundation for application of
      gene therapy to tumor clinical trial.

PMID- 11986704
TI  - [Study on the genetic variations of the major neutralization antigen VP7 of group
      A rotavirus type G1 in China].
AB  - OBJECTIVE: To study the genetic variations of the major neutralization antigen
      VP7 of group A rotavirus, type G1 in China. METHODS: Twenty-three isolates
      derived from seven cities (Beijing, Shenyang, Xinxiang, Shanghai, Shenzhen,
      Guangzhou and Chongqing) during the period of 1988-1998 were analyzed for the VP7
      cDNA sequences. RESULTS: An obvious homology was observed in amino acid sequences
      of VP7 in the 23 isolates. Compared with the standard strain Wa, the variations
      were found at the position of aa 41, 49, 57, 65, 68, 74, 94, 97, 147, 170, 217,
      218, 268, 281 and 291, respectively, and all of these were located in the
      variable region(VR)3,4,5,7,8 as well as in the C-terminal of the peptide. There
      seemed to be no remarkable divergence among the samples collected from different
      cities and all of them shared the same genetic lineage with the strain Jpn-417,
      though there might be one or two amino acid substitutions as time passed. When
      detected simultaneously with ELISA using G1 serotype-specific monoclonal
      antibody, the location of amino acid 91 was found presumably related to the
      neutralization epitope in VP7 of the type G1. Variations at some position may be
      resulted in the change of electropherotype. CONCLUSIONS: The results indicated
      that the recent isolates with representative genetic and antigenic features
      should be used to develop effective vaccines, and the antigenic variations should
      be monitored periodically.

PMID- 11986705
TI  - [Comparative study on antibody levels of vaccination group and control group
      after 4 years of immunized with type B inactivated vaccine against hemorrhagic
      fever with renal syndrome].
AB  - OBJECTIVE: To compare the antibody level of vaccine group and control group in a
      randomized, controlled trial of type B inactivated vaccine against hemorrhagic
      fever with renal syndrome(HFRS) in Jiande County of Zhejiang Province and to find
      out if there is enhancement of subclinical infection about type B inactivated
      vaccine against HFRS. METHODS: The number of sera collected (July 1994-July 1998)
      in vaccine group immunized type B inactivated vaccine against HFRS and control
      group were 305 and 283 persons in Jiande County respectively, and indirect
      immunofluorescent antibody method(IFAT) was used for testing the titer of HFRS
      IgG in sera. The cut-off values were determined on IFA titer of the second sera
      in control group with positive and negative IFA before vaccine was given
      respectively, and the subclinical infection of positive and negative IFA of the
      first sera in vaccine group was evaluated. RESULTS: When taking different cut-off
      values of subclinical infection, there were no statistical differences in HFRS
      IFA positive rates between vaccine group and control group of positive IFA in the
      first sera. In vaccine group and control group of negative IFA before vaccine
      given, also the IFA positive rates were not statistically different in these
      groups. There were no statistical differences of IFA GMT and IFA sero-negative
      rate between vaccine group and control group. CONCLUSIONS: The investigation
      showed there was no statistical difference in antibody level between vaccine
      group and control group, so there could not be enhancement of subclinical
      infection of vaccine group receiving type B inactivated vaccine against HFRS.

PMID- 11986706
TI  - [Expression of hepatitis B virus antigen in brain tissue from liver cirrhosis
      patients with hepatitis B and its significance].
AB  - OBJECTIVE: To investigate the expression of hepatitis B virus (HBV) antigen in
      brain tissue from liver cirrhosis patients with hepatitis B and explore its
      significance. METHODS: HBsAg and HBcAg were detected in the brain tissue from 70
      liver cirrhosis dead patients with hepatitis B by S-P immunohistochemical assay,
      and the relationship between the expression of HBV antigen in brain tissue
      testing and clinic and pathology was analyzed. RESULTS: 30 patients (42.89%) were
      positive for HBV antigen. Among them, 24 patients (34.29%) were positive for
      HBsAg and 18 patients (25.71%) were positive for HBcAg. HBV antigen was mainly
      found in cytoplasm and distributed in neurons, neurogliocytes and vascular
      endothelial cells. The positive cells were distributed separately, scatteredly or
      focally. The expression of HBV antigen was not associated with the serum level of
      HBV replication but associated with the occurrence of hepatic encephalopathy (HE)
      and the severity of brain tissue pathologic lesions of HE. CONCLUSIONS: The
      results indicate that HBV infection develop in brain tissue from liver cirrhosis
      patients with hepatitis B and HBV may replicate in it. HBV infection in brain
      tissue may p lay an important role in occurrence and development of HE from liver
      cirrhosis patients with hepatitis B.

PMID- 11986707
TI  - [The inhibitory effect of decomposed Chinese traditional medicine Chaihu on
      Coxsackie B virus(CVB3m) replication and its influence on cell activity].
AB  - OBJECTIVE: To study the anti-Coxsackie B virus (CVB3m) action of Chaihu(XCT) and
      its decomposed herb soups No.1 and No.2 in vitro, and also their protective
      effect on cells. METHODS: The anti CVB3m and cell protection effects of XCT and
      its decomposed herb soups No.1 and No.2 were observed by the methods of micro
      cell culture and neutral red ingestion, taking cytopathic effect and cell
      activity as judgments of medicine toxicity and virus replication. RESULTS: The
      non-toxic concentrations of XCTand its decomposed herb soups No.1 and No.2 had no
      apparent influence on HeLa cell activity, on the contrary, in certain range of
      concentrations, they could promote cell growth and cell activity. In therapeutic
      cell group, XCT and its decomposed herb soups No.1 and No.2 all had apparent
      inhibitory effect on CVB3m replication, especially the decomposed No.1 showing an
      inhibitory rate of 107.6%. Under the same decomposed No.1 concentration(1.5
      mg/ml), the viral inhibitory rate of the preventive therapeutic cell group was
      much higher than that of the therapeutic cell group, reaching as high as 128.1%.
      In virus adsorbed cell group, the CVB3m was also obviously inhibited by the XCT
      and decomposed No.1 and No.2. CONCLUSIONS: By comparing the effects on cell
      protection and virus replication of XCT and its decomposed herb soups No.1 and
      No.2, it identifies that XCT can protect cells against virus infection and
      directly kill the CVB3m, this Chinese herb medicine may be applied clinically for
      preventing and curing of viral myocarditis.

PMID- 11986708
TI  - [The influential factors on DNA cycle sequencing and data evaluation of practical
      example].
AB  - OBJECTIVE: To study some factors that may influence DNA sequencing by analyzing
      2040 sequencing samples retrospectively. METHODS: The effects of DNA templates,
      primers, cycle sequencing reactions as well as purification methods were
      comparatively analyzed. RESULTS: 70 percent of sequencing failure is caused by
      DNA template. Characteristics of data from poor template preparation include top
      heavy with a short read length, acceptable signal with some noise peaks (Ns),
      weak signal, overall noise and flat lines or no signal. The ineffective primers
      can cause 15.4 percent sequencing failure. Possible explanations include primer
      mismatches and low Tm value. CONCLUSIONS: The quality of template DNA can have a
      major impact on the quality of the DNA sequencing. Purification of the extension
      products is absolutely necessary in DNA sequencing, and isopropanol precipitation
      is highly recommended for this procedure.

PMID- 11986709
TI  - [Establishment of detection test for hepatitis C virus antigen].
AB  - OBJECTIVE: To establish the enzyme linking immunosorbent assay (ELISA) test with
      the specific monoclonal antibody (McAb) for detecting the hepatitis C virus (HCV)
      antigen so as to study the possibility of HCV antigen detection from plasma and
      serum samples. METHODS: Among the McAbs against HCV core and NS3 region, several
      kinds of combination models were analyzed to choose the optimal one. 348 samples
      from volunteer donors were tested by this test to calculate the cutoff value. 371
      samples, among which 146 samples were positive to anti-HCV and 225 ones were
      negative to anti-HCV, were screened. The antigen positive samples were confirmed
      by HCV nested PCR. RESULTS: The model of detection test was constructed with the
      C39,C7-6 as capture McAb and C39,C7-57 as HRP Conjugated McAb. This test could
      detect the C7 antigen to 5 ng/ml, and its cutoff value was determined as the
      average value of negative control by adding 0.25. Eleven of 146 samples positive
      to anti-HCV and 16 of 225 ones negative to anti-HCV were positive to HCV antigen.
      Among these 27 antigen positive samples, there were 23 positive to HCV RNA by PCR
      detection. CONCLUSIONS: With this HCV antigen detection test, some of samples
      positive to HCV antigen can be found from plasma positive to and negative to anti
      HCV and be confirmed by PCR. It is shown that it is possible to detect HCV
      antigen directly from plasma samples and it is important for HCV basic research
      and for control of transmission of HCV.

PMID- 11986710
TI  - [Detection of serum free insulin-like growth factor 1 in patients with chronic
      viral hepatitis].
AB  - OBJECTIVE: To evaluate the serum free insulin-like growth factor 1 (IGF-1) level
      and its relation with the severity and prognosis in patients with chronic viral
      hepatitis, liver cirrhosis and severe chronic hepatitis. METHODS: Serum free IGF
      1 was detected by ELISA in 43 patients with chronic viral hepatitis, 20 with
      liver cirrhosis and 12 with chronic severe hepatitis. RESULTS: Serum free IGF-1
      was significantly decreased in patients with liver cirrhosis and severe chronic
      hepatitis. Five patients with chronic severe hepatitis whose serum free IGF-1 was
      lower than 0.2 ng/l died during follow-up. Four patients whose serum free IGF-1
      above 0.3 ng/l survived. Serum free IGF-1 was significantly reduced in patients
      with albumin lower than 30 g/l. CONCLUSIONS: Serum free IGF-1 is decreased in
      patients with liver cirrhosis and severe chronic hepatitis and it can predict the
      prognosis of patients with severe chronic hepatitis.

PMID- 11986711
TI  - [Analysis and applications of a PrP antibody elicited by synthesized human PrP
      peptides].
AB  - BACKGROUND: To further study the immuno-reactivity and specificity of a PrP
      antibody elicited by synthesized human PrP peptides. METHODS: Construction of a
      plasmid which expresses a N-terminus deleted human PrP protein and purification
      of this truncated protein. The prepared PrP antibody was tested for reaction with
      various prokaryotic expressed human PrP proteins,including the full-length
      protein,the N-terminus-and C-terminus-truncated proteins with Western blot. The
      antibody was also used in the immunofluorescence assays to identify the PrP
      proteins expressed from the cell lines transfected with human PrP genes.
      Moreover,the brain tissues from scrapie agents-infected hamsters and a CJD
      patient were extracted and the proteinase K-resistant PrP-res were analyzed with
      the prepared antibody. RESULTS: The PrP-peptide elicited antibody could recognize
      both prokaryotic and eukaryotic expressed human PrP proteins, as well as the PrP
      res proteins in the brain tissues both from the scrapie-infected hamsters and CJD
      patient. CONCLUSIONS: The tested antibody possesses eligible immuno-reactivity
      and specificity and can be used for diagnosis of CJD in the clinical work.

PMID- 11986712
TI  - [Expression of baculovirus recombinant HPV16L1 and L2 capsid proteins in insect
      cells].
AB  - BACKGROUND: To express capsid proteins of HPV16 in insect cells system. METHODS:
      Recombinant baculovirus stocks were generated by cotransfection with baculovirus
      DNA and baculovirus recombinant transfer plasmids. The expression of aimed
      proteins in insect cells were confirmed by using SDS-PAGE and Western blot.
      RESULTS: Two stable strains of recombinant baculovirus expressing HPV16L1 protein
      alone and co-expressing HPV16L1 plus L2 proteins were obtained. The L1 and L2
      ORFs of HPV16 produced proteins of 57000 and 97000, respectively. The yield of L1
      protein was about 25%-30% of the total proteins of the insect cell. CONCLUSIONS:
      L1 and L2 proteins of HPV16 could be expressed with high efficiency in insect
      cells via recombinant baculoviruses.

PMID- 11986713
TI  - [Production of HPV 16 major capsid protein L1 with baculovirus expression
      system].
AB  - BACKGROUND: To obtain human papillomavirus type 16(HPV 16) major capsid protein
      L1 with baculovirus expression system. METHODS: Using pFb1 as a vector,a
      recombinant baculovirus expressing plasmid,which contains HPV16L1 gene
      sequence,was generated. The constructed virus was infected into an insect cell
      line Sf9. RESULTS: After incubating at 27 degrees for 72 hours, the infected
      cells were collected and total cellular poteins were extracted. SDS-PAGE assay
      revealed a roughly 56 000 expressed protein and Western blot confirmed that the
      expressed protein arose from HPV16L1. CONCLUSIONS: HPV16 later protein L1 could
      be efficiently expressed with baculovirus expression system,and the expressed L1
      protein remains to have good immunoreactivity. This study may supply a basic work
      for preparing virus-like particle and prophylactic HPV subunit vaccines.

PMID- 11986714
TI  - [Expression of the human papillomavirus type 58L1 capsid protein in E.coli and
      preparation of the HPV58 L1 mouse antiserum].
AB  - BACKGROUND: Human papillomavirus type 58 (HPV58) has been shown to be one of the
      most important highly-oncogenic, risky HPV types. The present study aimed at
      investigating the expression of the HPV58 L1 major capsid protein by E.coli and
      preparation of HPV58 L1 antiserum. METHODS: The full length L1 coden region of
      HPV58 L1 was amplified by PCR, the cloned, sequenced. The expression vector
      pRSETB58 L1 was constructed to produce HPV58 L1 protein. The protein expressed
      was purified by SDS-PAGE, and used to immunize BALB/c mice. RESULTS: HPV58 L1
      protein was expressed in E. coli, which has cross reaction with anti-HPV16 L1
      antibody. The mouse anti-HPV58 L1 antibody was obtained and used to test the
      HPV58 L1 protein expressed in insect cell. CONCLUSIONS: HPV58 L1 major capsid
      protein was efficiently expressed in E. coli. The mouse anti-HPV58 L1 specific
      antibody was prepared, which can be used to test the HPV58 L1 protein expressed
      in eukaryotic cell.

PMID- 11986715
TI  - [Malignant transformation of monkey kidney epithelial cell induced by EBV BARF1
      gene and TPA].
AB  - BACKGROUND: To study the effect of Epstein-Barr virus (EBV) BARF1 gene alone and
      synergistic effect of the gene and TPA in carcinogenesis. METHODS: PT1 and PT7
      cell line which were immortalized monkey kidney epithelial cells induced by the
      BARF1 gene of EB virus.PT1 and PT7 cell were cultured with 5 ng/ml TPA for two
      weeks. Then the nude mice and scid mice were injected with PT1, PT7, PT1+TPA,
      PT7+TPA cells, respectively. RESULTS: The immortalized PT1 and PT7 cells could
      not develop the tumor in nude mice, but could develop the tumor in scid mice
      (severe combined immune deficiency mice). It took about 45-60 days for
      development of tumor. After adding the tumor promoter TPA, the PT1 and PT7 cells
      developed the tumor either in nude mice or scid mice. It needed about 20-22 days
      in nude mice and 5-7 days in scid mice for development of tumor. PCR
      amplification revealed EBV-BARF1 gene in tumor tissues. CONCLUSIONS: EB virus
      BARF1 gene is another oncogene. Malignant transformation of the primary monkey
      kidney epithelial cell can be induced with BARF1 gene,even without tumor
      promoter.

PMID- 11986716
TI  - [Establishment and characterization of three transplantable tumors of
      nasopharyngeal carcinoma in Scid mice].
AB  - BACKGROUND: To establish several transplantable tumors of nasopharyngeal
      carcinoma (NPC) in order to provide suitable models for study of EBV specific
      immunity and its application in treatment of NPC. METHODS: Balb/C nude mice and
      scid mice were used as transplantation host. Tumor tissues were obtained with
      forceps from nasopharyngeal tumors of twenty six untreated NPC patients and
      transplanted subcutaneously in axilla or back of mice with puncture trocar.
      Characteristics of the established transplantable tumors including the
      transplanting efficiency, growth rate, gross appearance morphology under optic
      microscope and electron microscope and karyotypes chromosome were investigated.
      Detection of LMP-1 as well as LMP-2 were performed for the transplantable tumors
      and cell lines with immunohistochemical methods. RESULTS: Three transplantable
      tumors were successfully established from 26 specimens of human nasopharyngeal
      carcinoma and mamed as CSNET-1, CSNET-2 and CSNET-3. The CSNET-1 was primarily
      generated in nude mice and then transplanted to scid mice after 3 passages. To
      date the CSNET-1, CSNET-2, CSNET-3 have been passed to 11th generation (23
      months), 14th generation (17 months) and 9th generation (16 months),
      respectively. The overall success rates of transplantation were 91% (39/43), 97%
      (29/30) and 94% (34/36); The median time of latent growth were 23, 38 and 20
      days;and longest persistence of tumor in vivo were 93, 38 and 44 days,
      respectively, for the above tumors. The karyotypes of all transplantable tumors
      displayed as typical human origin with hyperdiploid chromosomal and multiple
      structure aberration. Histologically, the tumors possess the characteristics of
      poor differentiated squamous carcinoma under either microscope or electron
      microscope. Some particles minimizing mature EBV were found in CSNET-1 under
      electron microscope. Either LMP-1 or LMP-2 were detectable in CSNET-1, CSNET-2,
      and CSNET-3 by immunohistochemical test. CONCLUSIONS: The transplantable tumors
      CSNET-1, CSNET-2 and CSNET-3 are of human origin and able to pass steadily in
      scid mice. They possess the characteristics of poorly differentiated squamous
      carcinoma similar to their prime tumors in human and express EBV LMP-1 and LMP-2.
      These tumors seemed to be suitable models in the study of immunotherapy for NPC.

PMID- 11986717
TI  - [Nucleotide sequence of the noncoding regions of measles virus stain CC-47 and
      comparison with other measles viruses].
AB  - BACKGROUND: To determine the nucleotide sequence of noncoding regions of Measles
      virus strain Changchun-47 (CC-47) and to compare them with other measles virus
      for revealing some vaccine-related information. METHODS: Six overlapped
      fragments, that covers complete genome of CC-47 were amplified by using RT-PCR,
      all of the amplified fragments have been cloned and sequenced. RESULTS: Seven
      noncoding regions lie in the genome sequence of CC-47 separated by six structure
      genes. The noncoding regions of CC-47 contain 1791 nucleotides totally. Comparing
      of the noncoding regions of CC-47 with other wild type strains and five Edmonston
      derived vaccine strains, four nucleotide substitutions were shared by nearly all
      vaccine strains. Two of these were in the genomic 3  terminal transcriptional
      control region: position 26 (U->G), 42 (U->G); the other were in the F mRNA 5 
      untranslated region of M/F intergenic region. These site substitutions may
      influence the efficiency of mRNA synthesis, processing, and translation, as wel l
      as genome replication and encapsidation. CONCLUSIONS: The nucleotide
      substitutions shared by different genotype measles virus vaccine strains may be
      related to virus growth in semipermissive cell or process of attenuation, which
      provide useful data for molecular epidemiology of measles virus. The nucleotide
      substitutions for attenuation were involved in several regions other than one
      definite region.

PMID- 11986718
TI  - [HIV genomic mutation on antiretroviral therapy].
AB  - BACKGROUND: To study the characteristics of HIV genomic mutation on
      antiretroviral therapy. METHODS: HIV DNA and HIV RNA were detected by using Taq
      PCR, RT-PCR, LD-PCR, hybridization, and oligonucleotide 32P- probes against gag,
      tat, nef, LTRU3, etc. RESULYS: The HIV RNA load in serum declined significantly,
      CD4 lymphocyte count increased, copies of gag region of HIV DNA decreased, and
      full-length HIV DNA disappeared. Bands showing gag segments hybridized with 32P
      probe appeared negative or less clear in some cases after antiretroviral therapy.
      However, the regions hybridized with probes Xho-nef and LTR U5 were apparently
      enhanced and some drawbands were seen. CONCLUSIONS: HIV gene may experiece
      obvious mutation on antiretroviral therapy.

PMID- 11986719
TI  - [Molecular epidemiological characterization of rabies virus isolated from
      Guangxi].
AB  - BACKGROUND: To analyze the genotype of rabies virus isolated from different areas
      in Guangxi at different time. METHODS: mRNA of 8 Guangxi isolates, 1 Anhui
      isolates and 10 isolates from different countries of rabies virus were amplified
      by reverse transcription polymerse chain reaction (TR-PCR),and the products were
      sequenced. Phylogenetic analysis was carried out by phylip program. RESULTS:
      Phylogenetic analysis showed that 8 Guangxi isolates were related regionally, the
      homologic difference was lower than 2% among the isolates of the same area;
      higher than 15% among the isolates of two different areas.8 Guangxi isolates
      belonged to genotype A1, A2 a and A2 b; 10 chb of Guangxi isolates and thbkrb
      2123 and thdg 2933 of Thailand isolates belonged to genotype A2 b, while Guangxi
      isolates were different from isolates of USA, Mexico and South Africa, which all
      belonging to genotype B. CONCLUSIONS: There are at least three groups of rabies
      virus based on limited sequencing of N gene in Guangxi.

PMID- 11986720
TI  - [Experimental and clinical studies of recombinant human growth hormone treatement
      of hypoproteinemia of liver cirrhosis patients].
AB  - BACKGROUND: To assess the effect of recombinant human growth hormone (rhGH)
      therapy to liver cirrhosis patients with hypoproteinemia. METHODS: 31 liver
      cirrhosis patients were treated with rh GH (0.25 IU/kg/day-) and 20 such patients
      with human albumin (10 g/day) as control all for 10 days. Serum levels of growth
      hormone (GH), insulin-like growth factor (IGF)-1 and albumin (ALB) were measured
      by radio-immunoassay before 24h and after 24h and 10 days of rhGH therapy. Serum
      levels of GH and IGF-1 of 10 age matched healthy subjects were also measured.
      RESULTS: As compared with healthy subjects, the pretreatment serum GH level of
      liver cirrhosis patients was high (4.96 +/- 3.97 vs 1.62 +/- 2.26, P <0.05), and
      the IGF-1 level was markedly lower (36.53 +/- 12.77 vs 56.95 +/- 16.46, P <0.01).
      After 10 days of rhGH administration, the serum IGF-1 and ALB levels of the
      treated group increased significantly as compared with the control group (P
      <0.01). CONCLUSIONS: Exogenous rhGH therapy can overcome the GH resistance of
      liver cirrhosis patient s and can increase significantly the serum albumin level
      as compared with the control group who were treated with human albumin only.

PMID- 11986721
TI  - [Study on the expression of endothelial nitric oxide synthase and its mRNA in
      liver tissues of patients with chronic hepatitis B].
AB  - BACKGROUND: To study the expression of endothelial nitric oxide synthase (eNOS)
      and its mRNA in liver tissues of patients with chronic hepatitis B (CHB) and the
      relationship between its expression and pathological changes of hepatic tissues
      and the clinical significance. METHODS: 48 cases of specimens of liver tissues
      with CHB were observed and analyzed using immunohistochemical method and in situ
      nucleic acid hybridization. RESULTS: eNOS was expressed in hepatocytes, sinusiod
      endothelial cells and vessel endothelial cells, being predominantly expressed in
      hepatocytes. The number and distribution of eNOS mRNA positive cells were
      similiar to those of its protein. Increase in expression of eNOS was correlated
      with degrees of inflammatory activity and fibrosis (r=0.6855 [P<0.05]; r=0.4828
      [P<0.05]; respectively), and with decreasing PA and ALB (F=3.4101 [P<0.05];
      F=9.1714 [P<0.0]). Changes of expression of TGF-alpha-R were parallel to those of
      eNOS. CONCLUSIONS: eNOS may be involved in pathological lesion of CHB by
      affecting the expression of TGF-R in liver tissues with CHB.

PMID- 11986722
TI  - [Hepatocyte targeted DNA carrier L-PEI: the lactosylated polyethyleneimine and
      transfection in vitro].
AB  - BACKGROUND: To develop a hepatocyte targeted DNA carrier for expression of IFN or
      delivery of antiviral antisense neucleic acid into hapatocytes. METHODS: The
      hepatocyte targeted lactosylated polyethleneimine (L-PEI) was prepared through
      reductive amination of PEI with lactose. The in vitro transfection experiment was
      conducted and the stability of the DNA complex in rat serum was evaluated.
      RESULTS: L-PEI can effectively deliver luciferase gene into the galactose
      receptor positive Huh-7 cells. The transfection can be specifically inhibited by
      the synthesized ligand-lactosaminated BSA. The complex of DNA/L-PEI is stable in
      rat serum with only little degradation observed after 30 minutes, while free DNA
      was destroyed completely. CONCLUSIONS: L-PEI can be used as an specific and
      efficient DNA carrier.

PMID- 11986723
TI  - [Relationship between cholinesterase, prothrombin activity and albumin and the
      pathology of the liver].
AB  - BACKGROUND: To investigate the relationship between serum cholinesterase, albumin
      and plasma prothrombin activity and the pathology of the liver in patients with
      viral hepatitis. METHODS: Totally 135 patients diagnosed as chronic hepatitis,
      cirrhosis and/or severe hepatitis with needle biopsy of liver were enrolled in
      this study. Serum cholinesterase and albumin of the patients were detected with
      enzyme rate method; meanwhile, their plasma prothrombin activity was detected
      with turbidimetry test. RESULTS: The percentage of decrease of the level of serum
      cholinesterase was higher than that of albumin and plasma prothrombin activity in
      chronic mild and moderate hepatitis; the level of serum cholinesterase, albumin
      and plasma prothrombin activity decreased gradually followed by the exacerbation
      of inflammatory reaction (P<0.001) and by the elevation of degree of fibrosis of
      the liver (P <0.001) their correlation coefficient was 0.720 to 0.778 (P<0.001).
      CONCLUSION: The level of serum cholinesterase could better a nd more sensitively
      reflect the synthetic function and the damage of the pathology of the liver than
      that of albumin and plasma prothrombin activity could do, they all negatively
      correlated with the pathology of the liver.

PMID- 11986724
TI  - [Relationship between intrahepatic HCV-specific CTL activity and response to
      interferon therapy in chronic hepatitis C].
AB  - BACKGROUND: To study the relationship between intrahepatic hepatitis C virus
      specific cytotoxic T lymphocyte (HCV-CTL) activity and response to interferon
      (IFN) therapy in chronic hepatitis C. METHODS: 45 patients with chronic hepatitis
      C who received IFN-alpha therapy were evaluated for HCV-specific CTL in the liver
      before treatment with standard chromium release assay. The relationship between
      treatment response and HCV-CTL activity was analyzed. RESULTS: HCV-CTL activity
      was detected in 20 (44.4%) of the 45 IFN-treated patients. Of the 42 patients who
      completed a 6-month course therapy, 19 had detectable HCV-CTL activity, 23 had no
      detectable HCV-CTL activity. After 6 months of IFN therapy, 18 of 42 (42.9%)
      patients received an end-of-treatment complete response (ETR). After 6-12 months
      of follow-up, 10 patients (23.8%) had a sustained response (SR). Of the 19
      patients with detectable HCV-CTL activity, 15 (78.9%) developed an ETR. In
      contrast, only 3 of the 23 patients with no detectable HCV-CTL activity developed
      an ETR to IFN (P <0.01). All the 10 patients who got a sustained response were
      those with detectable HCV-CTL activity. Conclusion The host immune response,
      particularly that mediated by CD8+ HCV-CTL, may be very important in determining
      the outcome of IFN therapy for the patients with chronic hepatitis C.

PMID- 11986725
TI  - [Study on applicability of hepatitis C virus serotyping].
AB  - BACKGROUND: To explore the applicability of HCV serotyping. METHODS: Enzyme
      immunoassay (EIA) was used to detect the serotypes of 148 patients with viral
      hepatitis C. RESULTS: 56.08%(83/148) patients were serotyped,of whom
      50.06%(42/83) were identified to be serotype 1,43.37%(36/83) serotype 2, and
      6.03%(5/83)mixed serotype 1 and 2. The sera from 70 HCV RNA-positive patients out
      of the 83 ones who were successfully serotyped were detected for genotyping. The
      results were completely consistent between serotyping and genotyping.
      CONCLUSIONS: Serotyping of HCV has its clinical applicable value.

PMID- 11986726
TI  - [Safety and immunogenicity of a new inactivated hepatitis A vaccine].
AB  - BACKGROUND: To evaluate the safety and immunogenicity of a new inactivated
      hepatitis A virus (HAV) vaccine. METHODS: In a randomized controlled trail thirty
      one HAV-seronegative adults were enrolled and randomly assigned to either study
      group or control group. Subjects in the study group were given 1000 units of the
      new inactivated HAV vaccine, with a booster at 3 months. Subjects in the control
      group were given 720 ELISA units Havrix, produced by SmithKline Beecham
      Biologicals, with a subsequent dose at 3 months. Local and systematic reactions
      and serum response to the vaccines were compared between the two groups. RESULTS:
      Mild local reactions were noted in one subject from the study group and two from
      the control group after primary vaccination. Mild systematic reactions were
      reported in two subjects from each group after primary vaccination and in one
      subject from the study group after booster vaccination. Seroconversion rates were
      94%, 100%, and 100% in the study group at 1, 3, and 4 (1 month after booster)
      month, respectively. The corresponding figures were 73%, 80% and 100% in the
      control group. Geometric mean antibody titers were 139.2 mIU/ml, 137.7 mIU/ml,
      and 1 066.7 mIU/ml at 1, 3, and 4 months,respectively, in the study group,and
      104.3 mIU/ml, 111.3 mIU/ml, and 760.7 mIU/ml in the control group. CONCLUSIONS:
      The new inactivated hepatitis A vaccine was safe and highly immunogenic.

PMID- 11986727
TI  - [Detection of anti-HAV, anti-HBV, anti-HCV and anti-HEV antibodies in the
      patients with sporadic acute hepatitis in Beijing during 1995-2000].
AB  - BACKGROUND: To investigate distribution of acute hepatitis A, hepatitis B,
      hepatitis C and hepatitis E in Beijing area. METHODS: Enzyme immunoassay (EIA)
      was used for detection of anti-HAV immunoglobulin M (IgM), HBsAg/anti-HBc IgM,
      anti HCV IgM/IgG and anti-HEV IgM/IgG. The samples were collected from the
      patients with sporadic hepatitis in Beijing city between 1995 and 2000. RESULTS:
      The total positive rate of IgM antibodies to the four hepatitis-viruses was 72.4%
      (155) among 214 patients with sporadic acute hepatitis; the positive rates for
      the 4 viruses were 29% (45) for anti-HAV, 18.1% (28) for anti-HBc, 3.9% (6) for
      anti-HCV and 49% (76) for anti-HEV among 155 patients with acute viral hepatitis.
      Nine patients were coinfected with two hepatitis viruses. CONCLUSIONS: 78% of
      patients with sporadic acute hepatitis were caused by enterically transmitted
      hepatitis viruses (A and E) in Beijing between 1995 and 2000, Hepatitis E had the
      highest rate. Coinfection with two hepatitis virus was found in the patient with
      intravenous drug abusers and cirrhosis or acute hepatitis.

PMID- 11986728
TI  - [Analyzing partial nucleotide and amino acid sequences of Chinese TTV isolates].
AB  - BACKGROUND: To investigate the prevalence of transfusion transmitted virus (TTV)
      and its sequence characterization in China. METHODS: TTV DNA was amplified by
      Semi-Nested-PCR, and the positive products were sequenced directly. RESULTS: The
      homology of partial nucleotide and amino acid sequences of 7 Chinese TTV isolates
      were 64.7%-98.4% and 62.7%-96.4% respectively when compared with Japanese
      isolate. Among 7 Chinese TTV isolates, the homology of partial nucleotide and
      amino acid sequences were 63.5%-98.4% and 60.2%-96.4% respectively. They
      differently belong to two genotypes and two subgenotypes. CONCLUSIONS: There
      exists TTV in China, and there might be several genotypes of Chinese TTV
      isolates.

PMID- 11986729
TI  - [HCV-PCR-Hybrid.ELISA for the detection of HCV RNA in serum samples from
      hepatitis patients].
AB  - BACKGROUND: To detect HCV RNA in serum samples from hepatitis patients by using
      the methods of HCV-Reverse transcription polymerase chain reaction and hybrid
      ELISA. METHODS: HCV RNA in serum samples was amplified by RT-PCR with one of the
      primer labeled with biotin. PCR amplified products were detected with microtiter
      plate hybridization with HCV specific probe, then determined with steptavidin-HRP
      assay. Anti-HCV in these samples was also detected with ELISA simultaneously.
      RESULTS: The positive rates of HCV RNA were 81.8% (72/88) in anti-HCV positive
      group and 57.9% (88/152) in the whole patients group. Serum HCV RNA and anti-HCV
      positive rates were compared and the consistent rate was 78.9% (120/152, P>0.05).
      The positive rate of HCV RNA was higher in H.ELISA (57.9%, 88/152) than that in
      electrophoresis (35.5%, 54/152)(P<0.01). CONCLUSIONS: The HCV-PCR-H.ELISA was a
      sensitive, specific, stable, semi-quantitative and easy to operate method. This
      HCV RNA detection was especially beneficial to early diagnosis during viramia
      period and was helpful for the evaluation of anti-HCV therapy.

PMID- 11986730
TI  - [Nucelotide sequence of an ECHO virus isolated from a meningiti].
AB  - BACKGROUND: To determine the nucleotide sequences of W strain (Zhaoyuan/W/87)
      isolated from a meningitis patient, and compare them with the sequences of
      relational enteroviruses. METHODS: Virion RNA was transcribed into cDNA by
      reverse transcriptase, cDNA was amplified by PCR, the products of PCR were
      purified. Then RNA sequence analysis was performed by the dideoxynucleotide chain
      termination method using synthetic oligodeoxynucleotide primers. RESULTS: The
      partial nucleotide sequences of 5  UTR, region 2C and 3D of W strain
      (Zhaoyuan/W/87) were respectively 244, 275 and 353 nucleotides long. The complete
      nucleotide sequences of region VP1 were 876 nucleotides long coding 292 amino
      acids. In comparison with the VP1 sequence of two ECHO29 strains in Genbank
      through internet, the homogeneity of nucleotide sequence were 82.1% and 81.7%,
      that of amino sequence were 95.1% and 94.4%. CONCLUSIONS: W strain Zhaoyuna/W/87)
      was a mutation strain of ECHO29.

PMID- 11986731
TI  - [Detection of enterovirus RNA in cerebrospinal fluid from patients with aseptic
      meningitis and encephalitis and its clinical significance].
AB  - BACKGROUND: To study the pathogenicity of enterovirus (EV) infection in central
      nervous system and the method for its detection. METHODS: Using reverse
      transcription polymerase chain reaction (RT-PCR) and viral culture techniques to
      detect EV from 46 cerebrospinal fluid (CSF) samples of aseptic meningitis and
      encephalitis patients. The sensitivity and specificity of RT-PCR for EV RNA
      detection was affirmed by specific RNA identification of 40 strains of prototype
      enterovirus. RESULTS: By the virus culture method, 14 out of the 46 CSF sample
      were tested to beEV positive (26.1%) including 6 Echovirus type 2 (ECV2), 2
      Coxackie virus type B2 (CVB2), 2CVB6, 1 ECV3 and 1 ECV11. By RT-PCR method, 31 of
      46 CSF sample were tested EV RNA positive (67.4%) through amplified product
      agarose electrophoresis and northern blot hybridizition. The positive CSF
      included 14 samples that had been tested positive by virus culture and 17 samples
      that accounted for 53.9% of the 32 CSF samples which were negetive by virus
      culture. The sensitivity of RT-PCR was statistically higher than that of the
      virus culture method, Chi(2) =12.57, P <0.01. CONCLUSIONS: EV is known as
      important etiological agents of aseptic meningitis and encephalitis. RT-PCR is
      sensitivity, specificity and rapidity, it may be popularized as an effective
      method to the detection of enterovirus.

PMID- 11986732
TI  - [A preliminary study on infection of rabbits by human cytomegalovirus AD169
      strain].
AB  - BACKGROUND: To study the susceptibility of rabbit to human cytomeglavirus (HCMV)
      in vivo and in vitro. METHODS: Rabbit embryo lung (REL) cell monolayer were
      inoculated with HCMV AD169 strain. The cytopathic effect (CPE) was observed by
      microscope. HCMV antigen was detected by immunohistochemical method and viral
      particles were shown by electron microscopy. Human embryo lung (HEL) was taken
      control. Thirty New Zealand rabbits were divided into three groups randomly, two
      were virus groups (group1, group2) and one was inactivated virus group (group3).
      50 days later, the rabbits tissue lesions were observed by pathological
      techniques, HCMV DNA was analyzed by in situ hybridization. RESULTS: The CPE
      appeared 16 h post inoculation in REL cells as well as in HEL cells, at the same
      time, the HCMV antigen also was detected by immunhistochemistry and a large
      number of viral particles were manifested in the nucleus and cytoplasm of REL
      cells by electron microscope 36 h after virus inoculation. The extensive
      pathological damages in tissues of HCMV infected rabbits were observed and the
      viral DNA was also demonstrated in many tissues of HCMV infected rabbits.
      CONCLUSIONS: HCMV can infect REL cells and fulfil its replication cycle in vitro.
      HCMV AD169 strain can infect rabbits through intravenous injection and different
      infection models can be established by controlling the dosage of inoculated
      virus.

PMID- 11986733
TI  - [Cytomegalovirus infection associated with plasma endothelin and P-selectin in
      patients with essential hypertension].
AB  - BACKGROUND: To investigate the relationship between human cytomegalovirus (HCMV)
      infection and plasma endothelin and P-selectin in patients with essential
      hypertension. METHODS: Blood samples of 98 patients with essential hypertension
      were collected for HCMV IgM and IgG antibodies, plasma endothelin and plasma P
      selectin by chemiluminescence technique, radio-immunoassay and ELISA. RESULTS:
      The rates of positive HCMV IgM antibodies and positive rates for both HCMV IgM
      and IgG antibodies were 56.12% and 54.08%, respectively, which were higher than
      that of the control group (P=0.05). The level of plasma endothelin and P-selectin
      in patients with positive HCMV IgM antibodies was 95.53 +/- 5.06 ng/ml and 42.50
      +/- 3.28 ng/ml, respectively, which were higher than that in patients with
      negative HCMV IgM antibodies (71.60 +/- 4.34 ng/ml and 27.41 +/- 5.28 ng/ml) and
      that of the control group (48.77 +/- 5.96 ng/ml and 19.80 +/- 4.62 ng/ml).
      CONCLUSIONS: These results suggest that HCMV active infection may aggravate
      vascular endothelium lesi on in patients with essential hypertension and
      contribute to the increase of endothelin and P-selectin.

PMID- 11986734
TI  - [Detecting human papillomavirus type 6/11 with fluorescence quantitative PCR].
AB  - BACKGROUND: To study the human paillomavirus type 6/11 (HPV6/11) infectious
      status of patients with vaginitis. METHODS: Fluorescence quantitative PCR (FQ
      PCR) was used to measue HPV 6/11 DNA in 129 secretion samples. RESULTS: 47
      samples were positive with a positive rate of 36.43%; 39 of 47 samples had over
      105 copy/ml of the virus. CONCLUSIONS: Middle and old aged patients do not go to
      hospital until their virus infectious state becomes serious. FQ-PCR is suitable
      for clinical application because of its high sensitivity, rapidity and accuracy.

PMID- 11986735
TI  - [Study on etiology of clinically diagnosed non A-E hepatitis].
AB  - BACKGROUND: To study etiology of clinically diagnosed non A-E hepatitis. METHODS:
      HBV, TTV, human parvovirus B19, SENV DNA were detected by nested polymerase chain
      reactions (nPCR), while HGV, HCV RNA were tested by reverse transcription nested
      polymerase chain reactions (RT-nPCR). RESULTS: Of 60 patients with clinically
      diagnosed non A-E hepatitis, 30 (50.0%) were HBV DNA positive alone, 10 (16.7%)
      HBV and TTV DNA positive, 6 (10.0%) HBV and B19 DNA positive; 1 (1.7%) HBV, SENV
      DNA and HCV RNA positive, 1 (1.7%) HCV RNA positive alone, 1 (1.7%) HCV RNA and
      B19 DNA positive, 2 (3.3%) B19 DNA positive alone, 1 (1.7%) TTV DNA positive
      alone, and the remaining 8 (13.3%) negative for all viruses. All the 60 patients
      were HGV RNA negative. There were no differences in serum biochemical markers of
      hepatitis B patients with or without TTV or B19 virus infection. CONCLUSIONS: HBV
      is a major etiologic agent for the clinically diagnosed non A-E hepatitis. HGV,
      TTV, B19 and SEBV may not be associated with nonA-E hepatitis.

PMID- 11986736
TI  - [Structural and functional analysis of 2.2 kb spliced variant of hepatitis B
      virus genomes isolated from liver tissues from hepatocellular carcinoma
      patients].
AB  - BACKGROUND: To study the structure and function of 2.2 kb spliced variant of HBV
      genome from liver tissues of hepatocellular carcinoma patients. METHODS: HBV
      genomes were amplified by using PCR from paired hepatocellular carcinoma tissues
      and peritumor tissues. The 3.2 kb full-length HBV genome and 2.2 kb spliced
      variant were separately cloned and sequenced. Hep G2 cells were co-transfected
      with full-length HBV DNA and 2.2 kb spliced variant, and after transfection, HBV
      DNAs from intracellular core particles were harvested and specific primers were
      used in PCR to evaluate the interactions between spliced variant and full-length
      counterpart in replication. RESULTS: Semi-quantification by scanning density
      showed that 2.2 kb spliced variant was present in all tumor and peri-tumor
      samples studied. Sequence analyes revealed that the 5  terminus packaging signal
      for pregenomic and X and PreC/C genes were retained. When full-length HBV DNA was
      co-transfected with 2.2 kb, the replication signal of 3.2 kb HBV genome was
      increased 3-7 times. CONCLUSIONS: The 2.2 kb HBV spliced variant was present in
      liver tissues, and relative content was higher in tumor tissues than that in the
      peri-tumor tissues. This spliced variant could enhance the replication of full
      length HBV genome, which suggested the possible role of the variant in the
      pathogenesis of development of hepatocellular carcinoma.

PMID- 11986737
TI  - [In vitro evaluation on the effects of combined lamivudine (3TC) and Ara-AMP
      against hepatitis B virus].
AB  - BACKGROUND: To evaluate the inhibitive effect of combination of 3TC with Ara-AMP
      against HBV in vitro. METHODS: Used 2.2.15 cell as target cell. With
      radioimmunological technique and blot slot, the inhibitive effect of 3TC, Ara-AMP
      and the combination of both against the HBsAg, HBeAg and intracellular HBV DNA
      were investigated. RESULTS: The inhibitive ratio of Ara-AMP against HBsAg, HBeAg
      was 45.48% and 41.46% respectively when its concentration was 400.0 microgram/ml.
      Although 3TC also has inhibitive effect in its experimental concentration, its
      effect is weaker. When Ara-AMP 50.0 microgram/ml was combined with 3TC 1.25 and
      5.00 microgram/ml respectively, the inhibitive ratio against HBsAg were 19.92%
      and 17.32% respectively. Compared with using same concentration 3TC alone, the
      difference of results was significant (P<0.05). But when compared with using the
      same concentration Ara-AMP alone, the difference of results had no statistical
      significance (P <0.05). Remarkable inhibitive effects of combination of 3TC with
      Ara-AMP against HBeAg were n ot found. When 3TC 5.00 microgram/ml was combined
      with Ara-AMP 12.5 and 50.0 microgram/ml respectively, the inhibitive ratio
      against HBV DNA was 45.90% and 50.36% respectively. Comparing the content of HBV
      DNA in these groups with that of control group and the groups using the same
      concentration 3TC and Ara-AMP alone, the differences were significant (P <0.05).
      CONCLUSIONS: Combination of 3TC with Ara-AMP could enhance the inhibitive effects
      against HBV DNA.

PMID- 11986738
TI  - [Expression of thermal stable, soluble hepatitis E virus recombinant antigen].
AB  - BACKGROUND: To obtain thermal stable, soluble, biologically active hepatitis E
      virus recombinant antigen using thioredoxin fusion expression system. METHODS:
      HEV ORF2 gene fragment (6964-7126 nt) was inserted into thioredoxin fusion
      expression vector pThioHisA. The recombinant plasmid was transformed into E. coli
      BL21 strain. After induction with IPTG, cells were lysed and the supernatant was
      subjected to 80 degree treatment for 10 minutes. After centrifugation, the
      supernatant was tested by ELISA. RESULTS: SDS-PAGE analysis showed the
      thioredoxin. HEV fusion protein was highly expressed and was thermally stable,
      soluble. HEV specific ELISA confirmed this fusion protein possessing HEV specific
      antigenicity. CONCLUSIONS: Using thioredoxin fusion expression system, a soluble,
      thermal stable, biologically active HEV recombinant antigen was successfully
      expressed.

PMID- 11986739
TI  - [Immunogenicity of recombinant HEV ORF2 protein expressed in pichia pastoris].
AB  - BACKGROUND: To study to immunogenicity of recombinant HEV ORF2 protein expressed
      in pichia pastoris. METHODS: BALB/c mice were immunized with the recombinant HEV
      ORF2 protein. The ability of antiserum to bind HEV was tested using affinity
      capture reverse transcription polymerase chain reaction (RT-PCR). Moreover, the
      recombinant protein was used to immunize BALB/c mice by different routes with
      different adjuvants. Serum conversion rate of anti-HEV antibody and the ELISA
      titer were detected. RESULTS: The antiserum could capture native HEV for RT-PCR.
      As to the immunization effect, the immune response by intramuscular route was
      better than that of the intraperitoneal route. The protein with alum and CpG
      adjuvant could elicits more significant immune responses than using the alum
      adjuvant alone. The best way was to immunize with the protein with alum and CpG
      adjuvant by intramuscular route with a boosted injection on the 4th week after
      the first immunization. The ED50 was 0.023 microgram. This is the first report
      that the antibody elicited by recombinant HEV ORF2 protein expressed in pichia
      pastoris recognizes native HEV. High immunogenicity of this kind of ORF2 was also
      demonstrated by inducing strong immune response in mice with good ED50 result.
      CONCLUSIONS: The high immunogenicity of this kind of HEV ORF2 may make a
      foundation for the development of new type of hepatitis E vaccine.

PMID- 11986740
TI  - [Clinical and pathological characteristics and pathogenesis of autoimmune
      hepatitis].
AB  - BACKGROUND: To explore the clinical and pathological characteristics and
      pathogenesis of autoimmunohepatitis (AIH). METHODS: The serum and liver biopsy
      specimens and clinical data of 26 cases with patients with AIH were analyzed and
      scored according to the criteria of International autoimmune hepatitis (IAIHG,
      1999). The changes of dendritic cells (DC) in the liver tissues were observed
      with a panel of DC markers (CD-80/B7-1, CD-86/B7-2, CD-1a and HLA-DR) and
      immunohistochemistry, and the activation of hepatic stellate cells (HSC) and the
      expression of TGF-alpha were also detected. Liver tissue specimens from 10
      patients with chronic viral hepatitis B and C respectively and 5 normal liver
      specimens were chosen as controls. RESULTS: Mean aggregate scores of 26 AIH
      cases, including 21 cases of type B (80.8%) and 5 cases of type C (19.2%), which
      were 18.6 +/- 1.4 and 19.1 +/- 2.1 respectively. There were significant
      differences between the type B and type C in the average age levels of serum ALT
      and AST, and alpha-Glo (P <0.001 or P< 0.01 or P <0.05). Histological features of
      all the AIH liver tissues showed the lesions of chronic active hepatitis such as
      interface hepatitis/piecemeal necrosis (100%), obvious lobular inflammation (type
      B 95.2%, type C 100%), bridging necrosis (57.1% type B, 80.0% type C, P<0.05),
      rosetting of liver cells (71.4% type B, 100% type C, P<0.01), central lobular
      confluent necrosis (33.3% type B, 80.0% type C, P<0.001), predominant plasmacytic
      infiltration (type B 95.2%, type C 20.0%, P<0.001). The rates of increased and
      concentrated DC in the portal and lobular areas, especially in the active lesions
      in type B and type C AIH were 85.7% (18/21) and 5/5 respectively. It was found
      that DC and lymphocytes surrounded the hepatocytes which partly expressed HLA-DR
      antigen, while there were no or a few HLA-DR positive hepatocytes in controls.
      Meanwhile, the number of alpha-SMA positive HSC and the expression of TGF- were
      obviously increased in AIH liver tissues. CONCLUSIONS: Several clinical and
      pathological features of AIH were identified in this study. As an antigen
      presenting cell, DC might play an important role in the pathogenesis of AIH. In
      China, sub-type B of AIH might be more frequent than sub-type C and there were
      differences in clinical aspects, serology and pathology between the two types.

PMID- 11986741
TI  - [Preliminary evidence that a hepatitis E virus (HEV) ORF2 recombinant protein
      protects cynomolgus macaques against challenge with wild-type HEV].
AB  - BACKGROUND: To observe the protective effect of hepatitis E virus (HEV) ORF2
      recombinant protein expressed in prokaryote cell cynomolgus macaques (cynos)
      against challenging with wild-type HEV. METHODS: Cynos were immunized with HEV
      ORF2 recombinant protein and then challenged with wild-type HEV, the unimmunized
      cynos were used as control. Blood samples were collected and tested to see if
      there were dynamic changes of ALT and antibody to HEV before and after challenge
      with wild-type HEV. RESULTS: All the five unimmunized cynos re-presented
      hepatitis 3 weeks after challenging with wild-type HEV. However, all the five
      immunized cynos showed no hepatitis and pathological changes. CONCLUSIONS: Cynos
      can be efficiently protected by immunization with HEV ORF2 recombinant protein
      against wild-type HEV. This protein can be a promising candidate for HEV vaccine.

PMID- 11986742
TI  - [Correlation between IL-6 levels and polymerized human serum albumin ceptor
      (PHSAR) in serum of chronic hepatitis patients].
AB  - BACKGROUND: To investigate the relationship between interleukin-6 (IL-6) levels
      in serum and HBV replication and the role of IL-6 in liver damage in chronic
      hepatitis B patients. METHODS: Detected IL-6 levels and polymerized human serum
      albumin receptor (PHSA-R) in serum of different type of HBV markers positive
      patients and of different degree of chronic hepatitis B patients. RESULTS: The
      results showed that the serum IL-6 levels were increased significantly in PHSA-R
      positive patients than in PHSA-R negative patients in chronic hepatitis B
      (P<0.01). The serum IL-6 levels were correlated with the levels of PHSA-R
      (r=0.694, P<0.01), and the degree of symptoms. CONCLUSIONS: This study suggested
      that the IL-6 levels in serum of hepatitis B patients correlated HBV replication
      and the degree of liver damage, serum IL-6 levels may be used as a value
      indicating of HBV replication, the degree of symptoms and the effect of
      treatment.

PMID- 11986743
TI  - [Localization of hepatitis C virus core protein in the nucleus of peripheral
      blood mononuclear cells of hepatitis C patients].
AB  - BACKGROUND: To study the significance of the expression of HCV core protein in
      PBMC of patients with chronic hepatitis C and to evaluate the relationship
      between HCV core protein expression and clinical states. METHODS: Identification
      of HCV protein antigen (Ag) in PBMC of 66 hepatitis C patients by
      immunohistochemical method and clinical status of the patients with HCV protein
      positive expression were investigated. In 27 out off 66 patients the HCV RNA and
      HCV Ag in PBMC were detected with RT-PCR and immunohistochemical method. RESULTS:
      The HCV Ag (core+NS3) was identified in PBMC in 51 out of 66 patients (77.27%).
      It was also demonstrated that HCV core protein in nucleus showed strong
      expression and NS3 protein in cytoplasm showed weak expression. The expression of
      core protein in nucleus of PBMC were 35.29% in advanced chronic hepatitis
      patients, which was significantly higher than that from moderate cases (5.88%).
      CONCLUSIONS: This study suggested that the expression of PMBC-HCV core protein
      may be related to the clinical state of the patients. The nuclear expression of
      HCV core protein in PBMC of patients with hepatitis C may be related to the
      persistence and activity of the chronic hepatitis C virus and play an important
      role in the pathogenesis of cirrhrosis and hepatocellular carcinoma.

PMID- 11986744
TI  - [Detection of the expression of alpha3-integrin on hantavirus permissive cells].
AB  - BACKGROUND: To express and purify human alpha3-integrin to serve as the antigen
      to prepare its antibody and to separate the Vero cell clones without expression
      of alpha3-integrin. METHODS: The human alpha3-integrin gene was amplified by
      using RT-PCR, then subcloned into a pQE30 expression vector and expressed in E.
      coli. The gene expression was confirmed by Western blot assay. Rabbit was
      inoculated with purified antigen to stimulate the antibody generation. The target
      Vero cells were separated by negative selection using antibody plus complement
      mediated cytolysis. The separated cell clones were confirmed by
      immunofluorescence and Western blot assay. RESULTS: The alpha3- integrin gene was
      cloned and expressed effetively, Western blot assay revealed that the expressed
      protein held good immune reactivity. High titer antibody was generated. However
      the expression of alpha3-integrin was not detected on Vero, VeroE6, Hep-2, 2BS
      and 293 cells. CONCLUSIONS: The results of the study suggested that hantavirus
      has other receptors on Vero cells beside alpha 3-integrin.

PMID- 11986745
TI  - [Characterization of intertype specific epitopes on adenoviruses hexon].
AB  - BACKGROUND: To characterize the intertype epitopes on human adenovirus (HAdV)
      hexon. METHODS: Based on computerized analysis on adenoviruses sequence of
      genomic alignment, antigenicity prediction and 3-D structure characteristics of
      hexon subunit, several peptides of hexon of adenoviruses were chosen to be
      synthesized or recombinant proteins of the hexon were expressed in E. coli by use
      of PGEX-5X. To identify the existence of intertype epitopes, the antisera raised
      with synthetic peptides or purified recombinant proteins were analyzed with
      Western blot and immunofluorescent assay. RESULTS: The results of Western blot
      indicated that both peptide and recombinant antibodies showed specific
      reactivities with hexons of HADv-3, 4, 7 individually. Meanwhile, typical stain
      of immunofluorescence was found on HeLa cells infected with these HAdV by
      incubation with peptide as well as recombinant antibodies. Also, antibodies
      raised against peptide recognized the recombinant hexon protein in which a
      corresponding region of peptides was covered. CONCLUSIONS: Most of the predicted
      intertype epitopes of HAdV hexon wer e exclusively found in synthetic peptides
      and recombinant proteins. These intertype epitopes showed to be continuous and
      sequential which could be employed for development of antibodies of diagnostic
      use.

PMID- 11986746
TI  - [Molecular cloning,nucleotides sequence and transient expression of S and M
      genome segment of hantavirus strain 84Fli].
AB  - BACKGROUND: To sequence, analyze and express the nucleotide sequences of S and M
      segments of hantavirus strain 84Fli. METHODS: S and M segments of hantavirus
      84Fli strain were amplified by RT-PCR, the PCR products were cloned into plasmid
      pCR2.1-TOPOr. Three clones of each segment which have been sequenced were
      randomly selected. The coding region of S and M segments were amplified by PCR,
      and cloned into expressing vector pcDNA3.0. Transient expression of nucleocapsid
      protein, G1 and G2 glycoproteins in COS7 cells were performed by Lipofectin
      transfection. The expression of NP, G1 and G2 have been conformed by using
      immunofluorescence, Western blot and immuno-precipitation methods. RESULTS: The
      full length S and M segments cDNA have been amplified and cloned. The S and M
      segments of hantavirus strain 84Fli contained 1 688 and 3 616 nucleotides
      respectively. CONCLUSIONS: Deduced amino acid sequences of NP and glycoproteins
      revealed high homologue to other Hantaan viruses. NP, G1 and G2 proteins of 84Fli
      can be transiently expressed in COS7 cells.

PMID- 11986747
TI  - [Construction of recombinant vectors expressing antisense RNA to CCR5 and
      expression in eukaryotic cells].
AB  - BACKGROUND: To construct recombinant vector expressing antisense RNA to CCR5 in
      eukaryotic cells and obtain recombinant pseudovirus, which will be used to block
      HIV-1 infection. METHODS: The DNA fragment targeted against the initional part of
      CCR  5 mRNA translation was amplified by using RT-PCR from peripheral blood
      mononuclear cells (PBMCs) and cloned into retroviral vector pLXSN, then
      transfected into packaging cell (PA317) with lipofectAMINE. After 2-3 weeks
      selecting with G418, the pseudovirion in the survival cell's supernatant was
      detected with RT-PCR (FQ),then was used to infect NIH/3T3 cell. RESULTS: The
      psuedovirion packed from expression vector of sense/antisense RNA to CCR5 had
      infected NIH/3T3 cell successfully. The vector had incorporated into its genome
      and transcripted into RNA. CONCLUSIONS: The gene fragment of antisense RNA to
      CCR5 could be obtained from PBMCs and transfected into eukaryotic cell with
      retroviral vector. The results made a great foundation for studying its
      inhibiting effect on HIV-1 infection.

PMID- 11986748
TI  - [The establishment and application of antiviral screening model targeted on SAH
      hydrolase].
AB  - BACKGROUND: To establish a SAH hydrolase antiviral screening in vitro model for
      screening of broad spectrum antiviral agents. METHODS: SAH hydrolase was purified
      from rat livers by (NH4) 2SO4 fractionation, DEAE52,hydroxyapatite and Sephadex G
      100 chromatography successively. The activity of SAH hydrolase was estimated by
      radio labeled substrate in synthesis direction by TLC. RESULTS: Purified SAH
      hydrolase showed a single band in SDS-PAGE electrophoresis with silver nitrate
      staining, the apparent molecular weight is 45 000. The Km for adenosine is (6.32
      +- 0.17) micromol/L. The IC50 of S-DNPA, a known inhibitor of SAH hydrolase, was
      7.6 micromol/L estimated in our system. The structure and activity relationships
      shown by racemic and regiosomer analogs of S-DHPA indicated that the structural
      specificity of SAH hydrolase was high. 42 compounds had been screened in the
      system and no compound showed more inhibitory activity against SAH hydrolase than
      S-DNPA. CONCLUSIONS: An in vitro antiviral screening model has been established
      using SAH hydrolase. It can also be used to study kinetics of enzyme inhibition.

PMID- 11986749
TI  - [Dual gene amplification and selection system with dihydrofolate reductase and
      glutamine synthetase genes effectively increase the foreign gene expression].
AB  - BACKGROUND: To study the effect of gene amplification and selection system with
      DHFR plus GS and DHFR or GS gene on the foreign gene expression. METHODS: Using
      the N-terminal truncated hTPO(T184) gene as target gene, two plasmidsre were
      constructed: pDC- T184 and pGC-T184 where DHFR and GS gene were used respectively
      as the selective amplification marker. They were cotransfected into CHO dhfr
      cells to establish dual gene amplification and selection system of DHFR plus GS
      gen and respectively transfected to establish single gene amplification and
      selection system of DHFR or GS gene. Three selective methods in dual selective
      system to compare expression efficiency of hTPO were designed: the first method
      (DG) was to use drug pressure of MTX, then use MSX; the second method (GD) was
      reversed; the third method was simultaneously to use MTX and MSX as drug
      pressure. RESULTS: DHFR+GS dual system had not only higher gene amplification
      efficiency but also higher level expression. There was no distinct affect in
      different method of drug pressure. CONCLUSIONS: MTX plus MSX dual drug pressure
      in dual selection system was an efficient and simple method to increase the
      expression of foreign gene in mammalian cells.

PMID- 11986750
TI  - [Immune status of BALB/c mice and rubella virus JR23 strain infection of central
      nervous system].
AB  - BACKGROUND: To investigate the relationship between immune status and rubella
      virus (RV) infection of central nervous system (CNS). METHODS: BALB/c mice were
      given dexamethaxone and cytoxan before RV JR23 strain infection. Immune functions
      and RV invasion to CNS were assayed at 21 days postinfection via abdominal cavity
      and their relationship was analyzed. RESULTS: T cell functions of cytoxan group
      were obviously worse than those of other groups (P <0.05) by MTT method.
      Infection rates of dexamethaxone and cytoxan and the group without any
      intervention were 60%, 90% and 50% (P >0.05), respectively. Cellular immune
      functions of the mice with CNS infection were obviously worse than those of the
      mice without CNS infection (P <0.001). Specific antibodies (Ab) were assayed in
      all groups with ELISA and the results showed that there were no significant
      differences among groups (P >0.05), neither between the groups with and without
      CNS infections. CONCLUSIONS: RV infection of CNS may relate to cellular immune
      status before specific antibody was produced in the body.

PMID- 11986751
TI  - [Effect of bilirubin derivative on HIV-1 in vitro].
AB  - BACKGROUND: To study the effect of DTB against HIV-1, for developing anti-HIV
      drugs. METHODS: Different concentration of DTB was added to cell culture system
      after viral inoculation, MTT staining method for viable cells (MTT assay) and p24
      (ELISA) were used as markers to monitor the viral replication. RESULTS: The
      inhibition rates of DTB at concentrations 160, 80, and 40mg/ml were 93.0%, 56.2%
      and 18.1%, respectively. CONCLUSIONS: DTB could effectively inhibit HIV-1 in
      vitro.

PMID- 11986752
TI  - [Establishment of a sandwich ELISA method for detection of reporter
      chloramphenicol acetyltransferase gene].
AB  - BACKGROUND: To establish a sandwich ELISA method for detection of reporter
      chloramphenicol acetyltransferase (CAT) gene. METHODS: The full length sequence
      of CAT gene was amplified with PCR using plasmid pBLCAT6 as template, and
      inserted into the prokaryotic expression plasmid Pgex-2T. The purified fusion
      protein was emulsified with complete or incomplete Freund adjuvant and injected
      subcutaneously into rabbits. The antibody was labeled with biotin, and a sandwich
      ELISA technique with biotin streptavidin amplify system was established. Several
      CAT reporter plasmids containing different HPV 16 LCR sequences were generated
      and transfected transiently to monolayer cells in vitro. The cytoplasm proteins
      were extracted and the expressions of CAT were evaluated with the newly
      established ELISA assay. RESULTS: SDS-PAGE displayed that the molecular weight of
      the expressed fusion protein was about 54,000. The prepared antiserum was able to
      recognize the CAT protein expressed by mammalian cells or prokaryote cells. Under
      the control of different promoters and their regulate sequences,two to eight
      folds CAT expression increased were evaluated in transiently transfected
      mammalian cells by the newly established sandwich ELISA method. CONCLUSIONS: The
      established method could sensitively reflect the activities of the upstream
      promoters, as well as the influence of exchanges of nucleotides within the
      regulate region on the promoter activities. Therefore, it proposes a convenient
      assay for the studies using CAT as the reporter gene.

PMID- 11986753
TI  - [Generation of a series of recombinant herpes simplex viruses which can provide
      replicating and packaging functions for recombinant adeno-associated virus].
AB  - BACKGROUND: To construct a series of recombinant herpes simplex viruses that can
      provide replicating and packaging functions for recombinant adeno-associated
      virus (rAAV), and to select the strains possessing stronger functions for large
      scale production of rAAV. METHODS: A set of cosmids that represents the whole
      genome of HSV-1 was used to generate recombinant HSV-1 expressing rep and cap
      proteins of AAV-2. An ATG-to-ACG mutation in the start codon of AAV-2 rep protein
      was generated by site-directed mutagenesis. rep and cap genes, under control of
      their native promoters, with or without the ATG-to-ACG mutation in the start
      codon of rep, were inserted into the Xba   site of UL2 or UL44 genes,
      respectively, resulting in the recombinant cosmids cos6-rmc/  UL2, cos56-rc/ 
      UL44 and cos56-rmc/  UL44. Homologous recombination among the HSV-1 fragment on
      the recombinant cosmids and the rest fragments of HSV-1 genome resulted in three
      strains of recombinant HSV-1. Together with the one was constructed previously,
      there were four strains of recombinant HSV-1named HSV1-rc/  UL2, HSV1-rmc/  UL2,
      HSV1-rc/  UL44 and HSV1-rmc/  UL44 respectively. RESULTS: PCR detection confirmed
      the existence of   rep- gene in the genomes of all four strains of the
      recombinant HSV-1. Recombinant AAV was produced after infecting the AAV vector
      cell line that carrying the GFP expression cassette with the four strains of
      recombinant HSV-1 respectively. However, HSV1-rc/  UL2 and HSV1-rmc/  UL2
      produced much more rAAV than HSV1-rc/  UL44 and HSV1c/  UL44 did. CONCLUSIONS:
      All the four strains of recombinant HSV-1 support rAAV replication and packaging.
      HSV1  UL2 and HSV1-rmc/  UL2 that provide much stronger functions may be useful
      for large-scale production of rAAV.

PMID- 11986754
TI  - [Sero-and molecular epidemiology of the gene of different ORF of transfusion
      transmitted virus (TTV) in different population of China].
AB  - BACKGROUND: To investigate the distribution of anti-TTV antibody and the
      different ORF gene in different populations of China. METHODS: The antibody to
      TTV in sera collected from different population were detected by using ELISA and
      the different ORF genes were amplified with PCR. RESULTS: The positive rates of
      TTV ORF1 DNA, ORF2 DNA and the antibody in various populations were as follows:
      16.0% (12/75), 10.7% (8/75) and 25.3% (19/75) in paid blood donors; 10.0 (3/30),
      16.7% (5/30) and 16.7% (5/30) in patients with hepatitis A, 47.5% (19/40), 42.5%
      (17/40) and 22.5% (9/40) in patients with hepatitis B; 42.9% (15/35), 37.1%
      (13/35) and 28.6% (10/35) in patients with hepatitis C; 20.0% (3/15), 26.7%
      (4/15) and 13.3% (2/15)in patients with hepatitis D; 16.7% (2/12),16.7% (2/12)
      and 33.3% (4/12)in patients with hepatitis E; 23.8% (5/21), 38.1% (8/21) and
      23.8% (5/21) in patients with hepatitis G; 61.1% (11/18), 50.0% (9/18) and 44.4%
      (8/18) in patients with non A-G hepatitis, respectively. The positive rate of
      different ORF DNA had no significant difference. Significant differences were
      found in the positive rates of TTV DNA in various populations. There was no
      relationship between the TTV DNA and the antibody to TTV. CONCLUSIONS: The
      antibody to TTV and TTV DNA were found in every population of China. There was no
      significant difference in the positive rates of TTV DNA between ORF1 and ORF2.
      The positive rate in patients with non A-G hepatitis was higher than those in the
      other populations.

PMID- 11986755
TI  - [Establishment of an indirect enzyme-linked immunosorbent assay for detecting the
      specific IgM antibodies in patients with echovirus infection].
AB  - BACKGROUND: To provide a simple, specific and early serodiagnostic technique for
      the patients with aseptic meningitis caused by echovirus. METHODS: An indirect
      enzyme-linked immunosorbent assay (ELISA) has been developed to detect echovirus
      IgM and the specificity and availability of the assay were also examined.
      RESULTS: In 78 cerebrospinal fluid (CSF) specimens which came from the children
      with aseptic meningitis, the positive rate was 17.9(14/78). In 64 CSF collected
      from non-aseptic meningitis (bacterial meningitis and cerebral trauma), the
      positive rate was 1.56(1/64). In 5 CSF specimens which were ELISA positive, the
      positive rate of neutralization test (NT) was 4/5, all the specimens which were
      ELISA negative were NT negative. In this assay there was no cross-reaction with
      poliovirus, Coxsackie virus B type 1-6 and A type 7. By blocking and destructive
      test of specific IgM, all CSF specimens with ELISA positive became negative.
      CONCLUSIONS: The established indirect ELISA was specific and reliable. The te st
      was quick, simple and available, which is suitable for early and specific
      clinical diagnosis, and will be greatly significant to clinical treatment.

PMID- 11986756
TI  - [Inducible expression of non-structural protein 3 of hepatitis C virus in E.
      coli].
AB  - BACKGROUND: To express recombinant non-structural protein 3 of hepatitis C virus
      (HCV) in E. coli. METHODS: The non-structural 3 (NS3) region DNA fragment of HCV
      was amplified by polymerase chain reaction (PCR) and inserted into inducible
      proeukaryotic expressive vector pET 30C(+)at Bam H1/EcoR1 sites. The competent
      BL21 (DE3) E.coli was transformed, and then cultured and induced with IPTG. The
      expressed HCV NS3 protein was confirmed with ELISA and dot blot hybridization
      using HCV NS3-specific single chain Fv (ScFv) antibody. RESULTS: 1 893 bp DNA
      fragment of HCV NS3 coding region was amplified by PCR technique. HCV NS3
      expressive vector pET-NS3 was constructed. After transformation with pET-NS3 and
      induction with IPTG, recombinant HCV NS3 protein was expressed and confirmed by
      specific ELISA and dot blot hybridization. CONCLUSIONS: The recombinant HCV NS3
      can be expressed in E. coli.

PMID- 11986757
TI  - Gibberellin Metabolism and Its Regulation.

PMID- 11986758
TI  - Gibberellin Biosynthesis in Plants and Fungi: A Case of Convergent Evolution? 
AB  - As well as being phytohormones, gibberellins (GAs) are present in some fungi and
      bacteria. Indeed, GAs were first discovered in the fungus Gibberella fujikuroi,
      from which gibberellic acid (GA3) and other GAs are produced commercially.
      Although higher plants and the fungus produce structurally identical GAs, there
      are important differences in the pathways and enzymes involved. This has become
      particularly apparent with the identification of almost all of the genes for GA
      biosynthesis in Arabidopsis thaliana and G. fujikuroi, following the sequencing
      of the Arabidopsis genome and the detection of a GA-biosynthesis gene cluster in
      the fungus. For example, 3b-hydroxylation occurs early in the pathway in G.
      fujikuroi and is catalyzed by a cytochrome P450 monooxygenase, whereas it is
      usually the final step in plants and is catalyzed by 2-oxoglutarate-dependent
      dioxygenases. Similarly, 20-oxidation is catalyzed by dioxygenases in plants and
      a cytochrome P450 in the fungus. Even where cytochrome P450s have equivalent
      functions in plants and Gibberella, they are unrelated in terms of amino acid
      sequence. These profound differences indicate that higher plants and fungi have
      evolved their complex biosynthetic pathways to GAs independently and not by
      horizontal gene transfer.

PMID- 11986759
TI  - The Deoxyxylulose Phosphate Pathway for the Biosynthesis of Plastidic
      Isoprenoids: Early Days in Our Understanding of the Early Stages of Gibberellin
      Biosynthesis.
AB  - The identification of a novel pathway for isopentenyl diphosphate synthesis by
      Rohmer, Arigoni and colleagues in the early 1990's has led to a reappraisal of
      terpenoid biosynthesis in many organisms. It is now apparent that in plants there
      are two biosynthetic routes to isopentenyl diphosphate-the classical mevalonate
      pathway in the cytosol and the deoxyxylulose phosphate pathway in plastids.
      Sesquiterpenoids and sterols are predominantly synthesized in the cytosol by the
      mevalonate pathway whereas monoterpenoids, diterpenoids, the phytol side-chain of
      chlorophyll, carotenoids, and the nonaprenyl side-chain of plastoquinone-9 are
      synthesized within plastids by the deoxyxylulose phosphate pathway. Our
      assumptions that the early stages of gibberellin biosynthesis are plastid
      localized has led to several attempts to demonstrate that the deoxyxylulose
      phosphate pathway is the biosynthetic route to gibberellins. Although definitive
      evidence is still not available there is a growing body of evidence, mostly from
      transgenic plants and from the use of the inhibitor, fosmidomycin, that
      gibberellins are synthesized from deoxyxylulose phosphate-derived isopentenyl
      diphosphate. However, there is evidence that a small amount of cross-talk between
      the two pathways may occur, implying that the pathways are not totally
      autonomous. Implications for the regulation of the early stages of gibberellin
      biosynthesis are discussed.

PMID- 11986760
TI  - Auxin-Gibberellin Interactions and Their Role in Plant Growth.
AB  - Recently it was discovered that auxin promotes gibberellin (GA) biosynthesis in
      decapitated stems of pea (Pisum sativum L.) and tobacco (Nicotiana tabacum L.),
      and here we review the evidence for this interaction. We also discuss the
      possible relationship between auxin and the mechanisms by which bioactive GAs
      (such as GA1) regulate their own levels, and the implications of the auxin-GA
      interaction for the control of plant growth. It is now possible to envisage auxin
      as a messenger linking the apical bud with the biosynthesis of active GAs in the
      expanding internodes. Finally, new evidence is presented that the promotion of
      growth by GA1 does not depend on GA1-induced increases in auxin content.

PMID- 11986761
TI  - Light Regulation of Gibberellin Biosynthesis and Mode of Action.
AB  - Some phenotypic effects produced in plants by light are very similar to those
      induced by hormones. In this review, the light-gibberellin (GA) interaction in
      germination, de-etiolation, stem growth, and tuber formation (process regulated
      by GAs) are discussed. Germination of lettuce and Arabidopsis seeds depends on
      red irradiation (R), which enhances the expression of GA 3-oxidase genes (GA3ox)
      and leads to an increase in active GA content. De-etiolation of pea seedling
      alters the expression of GA20ox and GA3ox genes and induces a rapid decrease of
      GA1 content. Stem growth of green plants is also affected by diverse light
      irradiation characteristics. Low light intensity increases stem elongation and
      active GA content in pea and Brassica. Photoperiod controls active GA levels in
      long-day rosette (spinach and Silene) and in woody plants (Salix and hybrid
      aspen) by regulating different steps of GA biosynthesis, mainly through
      transcript levels of GA20ox and GA3ox genes. Light modulation of stem elongation
      in light-grown plants is controlled by phytochrome, which modifies GA
      biosynthesis and catabolism (tobacco, potato, cowpea, Arabidopsis) and GA
      response (pea, cucumber, Arabidopsis). In Arabidopsis and tobacco, ATH1 (a gene
      encoding an homeotic transcription factor) is a positive mediator of a phyB
      specific signal transduction cascade controlling GA levels by regulating the
      expression of GA20ox and GA3ox. Tuber formation in potato is controlled by
      photoperiod (through phyB) and GAs. Inductive short-day conditions alter the
      diurnal rhythm of GA20ox transcript abundance, and increases the expression of a
      new protein (PHOR1) that plays a role in the photoperiod-GA interaction.

PMID- 11986762
TI  - Gibberellins and Light-Stimulated Seed Germination.
AB  - Bioactive gibberellins (GAs) promote seed germination in a number of plant
      species. In dicots, such as tomato and Arabidopsis, de novo GA biosynthesis after
      seed imbibition is essential for germination. Light is a crucial environmental
      cue determining seed germination in some species. The red (R) and far-red light
      photoreceptor phytochrome regulates GA biosynthesis in germinating lettuce and
      Arabidopsis seeds. This effect of light is, at least in part, targeted to mRNA
      abundance of GA 3-oxidase, which catalyzes the final biosynthetic step to produce
      bioactive GAs. The R-inducible GA 3-oxidase genes are predominantly expressed in
      the hypocotyl of Arabidopsis embryos. This predicted location of GA biosynthesis
      appears to correlate with the photosensitive site determined by using R micro
      beam in lettuce seeds. The GA-deficient non-germinating mutants have been useful
      for studying how GA stimulates seed germination. In tomato, GA promotes the
      growth potential of the embryo and weakens the structures surrounding the embryo.
      Endo-b-mannanase, which is produced specifically in the micropylar endosperm in a
      GA-dependent manner, may be responsible for breaking down the endosperm cell
      walls to assist germination. Recently, a role for GA in overcoming the resistance
      imposed by the seed coat was also suggested in Arabidopsis from work with a range
      of seed coat mutants. Towards understanding the GA signaling pathway, GA response
      mutants have been isolated and characterized, some of which are affected in GA
      stimulated seed germination.

PMID- 11986763
TI  - The Interaction of Gibberellins and Photoperiod in the Control of Potato
      Tuberization.
AB  - Solanum tuberosum ssp. andigena plants require a short-day (SD) photoperiod for
      tuber formation, a process that is also affected by gibberellins (GAs). Grafting
      experiments have confirmed that the photoperiod is perceived in the leaves. Tuber
      formation, however, usually takes place in the underground stolons. In this
      review, photoperiod-dependent tuberization has been divided into five
      chronological events: SD photoperiod perception, short-term adaptive responses to
      SD conditions, generation and transport of tuber-inducing signal(s), tuber
      formation, and long-term adaptive responses to tuber growth. Within this frame of
      study, the interaction of GAs and photoperiod is revised. Similar to the
      flowering process in Arabidopsis, we suggest the existence of two independent
      pathways that control tuber formation: a photoperiod-dependent pathway and a GA
      dependent pathway. Nevertheless, photoperiod-dependent tuber formation requires
      the action of GAs at specific stages to orchestrate this complex process of
      development.

PMID- 11986764
TI  - Occurrence of Gibberellins in Vascular Plants, Fungi, and Bacteria.
AB  - The occurrence of GA1 to GA126 in vascular plants, fungi, and bacteria is listed.
      The data are discussed with reference to criteria for identification and to the
      frequency of occurrence of GAs in vascular plants.

PMID- 11986766
TI  - Women's knowledge and beliefs regarding breast cancer.
AB  - Approximately 20-30% of women delay for 12 weeks or more from self-discovery of a
      breast symptom to presentation to a health care provider, and such delay
      intervals are associated with poorer survival. Understanding the factors that
      influence patient delay is important for the development of an effective,
      targeted health intervention programme to shorten patient delay. The aim of the
      study was to elicit knowledge and beliefs about breast cancer among a sample of
      the general female population, and examine age and socio-economic variations in
      responses. Participants were randomly selected through the Postal Address File,
      and data were collected through the Office of National Statistics. Geographically
      distributed throughout the UK, 996 women participated in a short structured
      interview to elicit their knowledge of breast cancer risk, breast cancer
      symptoms, and their perceptions of the management and outcomes associated with
      breast cancer. Women had limited knowledge of their relative risk of developing
      breast cancer, of associated risk factors and of the diversity of potential
      breast cancer-related symptoms. Older women were particularly poor at identifying
      symptoms of breast cancer, risk factors associated with breast cancer and their
      personal risk of developing the disease. Poorer knowledge of symptoms and risks
      among older women may help to explain the strong association between older age
      and delay in help-seeking. If these findings are confirmed they suggest that any
      intervention programme should target older women in particular, given that
      advancing age is a risk factor for both developing breast cancer and for
      subsequent delayed presentation.

PMID- 11986765
TI  - Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel
      in patients with metastatic/advanced breast cancer pretreated with
      anthracyclines.
AB  - Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5
      fluorouracil preferentially at the tumour site. This randomised, phase II trial
      evaluated the efficacy and safety of capecitabine or paclitaxel in patients with
      anthracycline-pretreated metastatic breast cancer. Outpatients with locally
      advanced and/or metastatic breast cancer whose disease was unresponsive or
      resistant to anthracycline therapy were randomised to 3-week cycles of
      intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (22
      patients)) or a reference arm of i.v. paclitaxel (175 mg m(-2), (20 patients)).
      Two additional patients were initially randomised to continuous capecitabine 666
      mg m(-2) twice daily, but this arm was closed following selection of the
      intermittent schedule for further development. Overall response rate was 36% (95%
      CI 17-59%) with capecitabine (including three complete responses) and 26% (95% CI
      9-51%) with paclitaxel (no complete responses). Median time to disease
      progression was similar in the two treatment groups (3.0 months with
      capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4
      months, respectively). Paclitaxel was associated with more alopecia, peripheral
      neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse
      events were diarrhoea, vomiting and hand-foot syndrome. Twenty-three per cent of
      capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a >
      or =10% improvement in Karnofsky Performance Status. Oral capecitabine is active
      in anthracycline-pretreated advanced/metastatic breast cancer and has a
      favourable safety profile. Furthermore, capecitabine provides a convenient,
      patient-orientated therapy.

PMID- 11986767
TI  - A phase I dose-finding study of a combination of pegylated liposomal doxorubicin
      (Doxil), carboplatin and paclitaxel in ovarian cancer.
AB  - Standard chemotherapy for advanced epithelial ovarian cancer is a combination of
      platinum-paclitaxel. One strategy to improve the outcome for patients is to add
      other agents to standard therapy. Doxil is active in relapsed disease and has a
      response rate of 25% in platinum-resistant relapsed disease. A dose finding study
      of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first
      line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian
      tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and
      doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2);
      doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of
      21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with
      doxil being administered every other course (q 42). The dose-limiting toxicities
      were found to be neutropenia, stomatitis and palmar plantar syndrome and the
      maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2)
      and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not
      allow the doxil dose to be increased. Delivering doxil on alternate cycles at
      doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The
      recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175
      mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2),
      doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the
      recommended phase II doses but was short lived and not clinically important and
      non-haematologic toxicities were generally mild and consisted of nausea,
      paraesthesiae, stomatitis and palmar plantar syndrome.

PMID- 11986768
TI  - A dose-finding study of carboplatin-epirubicin-docetaxel in advanced epithelial
      ovarian cancer.
AB  - The docetaxel-carboplatin combination is active and well tolerated in patients
      with epithelial ovarian cancer. We added epirubicin to this combination to
      investigate additional benefits of anthracyclines in epithelial ovarian cancer.
      Twenty-one patients, FIGO Ic-IV, performance status 0-1, were treated in four
      dose cohorts. Docetaxel was fixed at 75 mg m(-2), carboplatin doses were AUC 4-5
      and epirubicin doses were 50-60 mg m(-2). Drugs were given on day 1, every 3
      weeks, except in cohort 3, where epirubicin was given on day 8. Dexamethasone was
      given prophylactically. One dose-limiting toxicity occurred in cohorts 1, 2 and
      4, two occurred in cohort 3. Complicated neutropenia occurred in two patients in
      cohorts 1 and 2 and one patient in cohorts 3 and 4. Two patients experienced
      grade III diarrhoea or stomatitis in cohort 1 and two in cohort 3. There were no
      treatment-related deaths. Grade II sensory neuropathy occurred in one patient. No
      cardiac toxicity or significant oedema was observed. The overall response rate
      was 36%, and 62% were CA125 responders. The predefined maximum tolerated dose was
      exceeded in cohort 3. The cohort 4 dose level (epirubicin 50 mg m(-2),
      carboplatin AUC 4, docetaxel 75 mg m(-2)), warrants further study.

PMID- 11986769
TI  - Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features
      in lung metastases.
AB  - Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be
      activated by the same biochemical stimulus; hypoxia. A correlation between these
      two parameters has been postulated. The objective of this study was to evaluate
      the relationship between Fluoro-desoxi-glucose uptake at positron emission
      tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose
      activity, expressed as a standard uptake value, and microvessel intratumoural
      density, were retrospectively calculated in a series of 43 lung metastasis
      resected in 19 patients. Primary sites were colorectal cancer in 16 metastases,
      sarcoma in eight, gynaecological in four and other sites in 15. The correlation
      between the two parameters was tested by logistic regression and multivariate
      analysis. Positron emission tomography scan was positive in 17 patients
      (sensitivity 89%). No correlation was observed between standard uptake value and
      microvessel intratumoural density in this series of lung metastasis. Positron
      emission tomography negative and positive nodules presented comparable value of
      microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was
      significantly correlated with nodules size and was higher in colon cancer
      metastasis than in sarcoma ones. Microvessel intratumoural density was
      independent from nodule size but significantly higher in sarcoma than in colon
      cancer metastasis. The lack of correlation was confirmed by multivariate analysis
      after adjustment for tumour type and nodules size. The present study demonstrated
      that positron emission tomography scan is positive in a high proportion of
      patients regardless of microvessel density. Glucose uptake and angiogenesis
      appear to be independent biological features in lung metastasis. This observation
      may have implications for future antiangiogenic therapies.

PMID- 11986770
TI  - Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients
      with renal cell carcinoma.
AB  - As regulators of malignant cell behaviour and communication with stroma,
      cytokines have proved useful in understanding cancer biology and developing novel
      therapies. In renal cell carcinoma, patients with inflammatory reactions are
      known to have poor prognosis. In order to elucidate the relation between renal
      cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin
      6, tumour necrosis factor alpha, interleukin-1beta, were measured. One hundred
      and twenty-two patients with renal cell carcinoma and 21 healthy control subjects
      were studied, and serum cytokine levels were measured using a highly sensitive
      ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis
      factor alpha and interleukin-1beta levels were 1.79+/-2.03, 2.74+/-0.94 and
      0.16+/-0.17 pg ml(-1), respectively. In the renal cell carcinoma patients, they
      were 8.91+/-13.12, 8.44+/-4.15 and 0.53+/-0.57 pg ml(-1), respectively, and
      significantly higher. In the comparison of stage, interleukin-6 level was
      significantly higher in the stage IV group compared to the other stage groups
      including the control group, while tumour necrosis factor alpha level was
      significantly higher in each stage group compared to the control group. As for
      grade, interleukin-6 level was significantly higher in the grade 3 group compared
      to the control, grade 1 and grade 2 groups, while tumour necrosis factor alpha
      level was significantly higher in each grade group compared to the control group.
      All cytokines had a positive correlation with tumour size. In regard to the
      correlation with CRP, all cytokines had a positive correlation with CRP, while
      interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6
      may be one of the factors for the poor prognosis of patients with renal cell
      carcinoma. In addition, tumour necrosis factor alpha may be useful in the early
      diagnosis of renal cell carcinoma and post-operative follow-up.

PMID- 11986772
TI  - Population mixing and childhood leukaemia and non-Hodgkin's lymphoma in census
      wards in England and Wales, 1966-87.
AB  - We found an increased risk of childhood leukaemia with higher levels of inward
      migration, particularly from outside the region (rate ratio=1.9, 95%CI: 1.2-2.9,
      P<0.01). This significant effect was observed only in urban areas, although a
      marked but non-significant effect was seen in affluent, rural areas.

PMID- 11986771
TI  - Tumour targeting of humanised cross-linked divalent-Fab' antibody fragments: a
      clinical phase I/II study.
AB  - Antibody engineering has made it possible to design antibodies with optimal
      characteristics for delivery of radionuclides for tumour imaging and therapy. A
      humanised divalent-Fab' cross-linked with a bis-maleimide linker referred to as
      humanised divalent-Fab' maleimide was produced as a result of this design
      process. It is a humanised divalent antibody with no Fc, which can be produced in
      bacteria and has enhanced stability compared with F(ab')(2). Here we describe a
      clinical study in patients with colorectal cancer using humanised divalent-Fab'
      maleimide generated from the anti-carcinoembryonic antigen antibody A5B7
      radiolabelled with iodine-131. Ten patients received an i.v. injection of iodine
      131-labelled A5B7 humanised divalent-Fab' maleimide, and positive tumour images
      were obtained by gamma camera imaging in eight patients with known lesions, and
      one previously undetected lesion was identified. True negative results were
      obtained in two patients without tumour. Area under the curve analysis of serial
      blood gamma counting and gamma camera images showed a higher tumour to blood
      ratio compared to A5B7 mF(ab')(2) used previously in the clinic, implying this
      new molecule may be superior for radioimmunotherapy. MIRD dose calculations
      showed a relatively high radiation dose to the kidney, which may limit the amount
      of activity that could be administered in radioimmunotherapy. However the
      reduction in immunogenicity was also a major advantage for A5B7 humanised
      divalent-Fab' maleimide over murine versions of this antibody suggesting that
      humanised divalent-Fab' maleimide should be a useful vehicle for repeated
      therapies.

PMID- 11986773
TI  - Cancer risks in childhood and adolescence among the offspring of immigrants to
      Sweden.
AB  - We used the nation-wide Swedish Family-Cancer Database to analyse the risk of
      nervous system tumours, leukaemia and non-Hodgkin's lymphoma in age groups 0-4
      and 0-19 years among Swedish-born offspring of immigrants. The study included 850
      000 individuals with an immigrant background, including European, Asian and
      American parents. We calculated standardised incidence ratios for the above three
      malignancies using Swedish offspring as a reference. Subjects were grouped by
      region or by selected countries of parental origin. No group differed
      significantly from Swedes in the occurrence of nervous system neoplasm or
      leukaemia. Offspring of Yugoslav fathers (SIR 2.27) and Turkish parents were at
      increased risk of non-Hodgkin's lymphoma. The highest risk was noted for non
      Hodgkin's lymphoma among young offspring (0-4 years) of two Turkish parents
      (6.87). The currently available limited data on rates for childhood non-Hodgkin's
      lymphoma in these countries do not explain the risk in the offspring of
      immigrants. Yugoslavs and Turks are recent immigrant groups to Sweden, and their
      offspring have been subject to much population mixing, perhaps leading to
      recurring infections and immunological stimulation, which may contribute to their
      excess of lymphomas.

PMID- 11986774
TI  - Daycare attendance and risk of childhood acute lymphoblastic leukaemia.
AB  - The relationship between daycare/preschool ("daycare") attendance and the risk of
      acute lymphoblastic leukaemia was evaluated in the Northern California Childhood
      Leukaemia Study. Incident cases (age 1-14 years) were rapidly ascertained during
      1995-1999. Population-based controls were randomly selected from the California
      birth registry, individually matched on date of birth, gender, race, Hispanicity,
      and residence, resulting in a total of 140 case-controls pairs. Fewer cases
      (n=92, 66%) attended daycare than controls (n=103, 74%). Children who had more
      total child-hours had a significantly reduced risk of ALL. The odds ratio
      associated with each thousand child-hours was 0.991 (95% confidence interval
      (CI): 0.984-0.999), which means that a child with 50 thousand child-hours (who
      may have, for example, attended a daycare with 15 other children, 25 h per week,
      for a total duration of 30.65 months) would have an odds ratio of
      (0.991)(50)=0.64 (95% CI: 0.45, 0.95), compared to children who never attended
      daycare. Besides, controls started daycare at a younger age, attended daycare for
      longer duration, remained in daycare for more hours, and were exposed to more
      children at each daycare. These findings support the hypothesis that delayed
      exposure to common infections plays an important role in the aetiology of
      childhood acute lymphoblastic leukaemia, and suggest that extensive contact with
      other children in a daycare setting is associated with a reduced risk of acute
      lymphoblastic leukaemia.

PMID- 11986775
TI  - Pregnancy and risk of renal cell cancer: a population-based study in Sweden.
AB  - Epidemiological findings indicate that hormonal influences may play a role in the
      etiology of renal cell cancer (RCC). The possible effect of childbearing remains
      enigmatic; while some investigators have reported a positive association between
      number of births and renal cell cancer risk, others have not. A case-control
      study, nested within a nation-wide Fertility Register covering Swedish women born
      1925 and later, was undertaken to explore possible associations between parity
      and age at first birth and the risk of renal cell cancer. Among these women a
      total of 1465 cases of RCC were identified in the Swedish Cancer Register between
      1958 and 1992 and information on the number of live childbirths and age at each
      birth was obtained by linkage to the Fertility Database. For each case, five age
      matched controls were randomly selected from the same register. Compared to
      nulliparous women, ever-parous women were at a 40% increased risk of RCC (Odds
      Ratio [OR]=1.42; 95% CI 1.19-1.69). The corresponding OR for women of high parity
      (five or more live births) was 1.91 (95% CI 1.40-2.62). After controlling for age
      at first birth among parous women, each additional birth was associated with a
      15% increase in risk (OR=1.15; 95% CI 1.08-1.22). The observed positive
      association between parity and renal cell cancer risk is unlikely to be fully
      explained by uncontrolled confounding, but warrants further evaluation in large
      studies, with allowance for body mass index.

PMID- 11986776
TI  - A prospective cohort study of cigarette smoking and the risk of endometrial
      cancer.
AB  - Case-control studies have shown inverse associations between cigarette smoking
      and endometrial cancer risk. However, two small prospective cohort studies have
      not clearly supported an association. Moreover, quantitative measures of smoking
      have been examined infrequently. Our aim was to study the association between
      smoking and endometrial cancer risk in a large prospective cohort. We used
      proportional hazards models to estimate hazard ratios relating cigarette smoking
      to endometrial cancer risk among 70 591 women aged 40-59 years at recruitment
      into a randomised controlled trial of mammography screening for breast cancer.
      During an average of 10.6 years of follow-up (751 833 person-years), a total of
      403 women were diagnosed with incident endometrial cancer. We found that a
      reduced endometrial cancer risk was evident only among women who currently smoked
      20 cigarettes per day or more (hazard ratio=0.62, 95% CI=0.42-0.92, P for
      trend=0.03). There was some suggestion of an inverse association with smoking
      duration, but this was less clear. The association did not vary with menopausal
      status, relative body weight, or the use of hormone replacement therapy, but it
      appeared to be stronger among parous than nulliparous women. The underlying
      biological mechanisms of this association remain unclear.

PMID- 11986777
TI  - Statin use, hyperlipidaemia, and the risk of breast cancer.
AB  - Hydroxymethyl glutaryl coenzyme A inhibitors ("statins") are carcinogenic in
      rodents and an increased incidence of breast cancer was reported among
      pravastatin users in one randomised trial. We conducted a case-control study in
      the General Practice Research Database to evaluate the risk of breast cancer
      among 50- to 79-year old women treated with statins for hyperlipidaemia. Case and
      control women were matched by age, general practice, duration of prescription
      history in the General Practice Research Database, and index date. Adjusting for
      history of benign breast disease, body mass index, and use of hormone replacement
      therapy, women currently treated with statins had an estimated relative risk for
      breast cancer of 1.0 (95% confidence interval 0.6-1.6) compared to women without
      hyperlipidaemia. Untreated hyperlipidaemia was associated with an increased risk
      of breast cancer (estimated relative risk 1.6; 95% confidence interval 1.1-2.5).
      The estimated relative risk among women currently receiving only non-statin lipid
      lowering drugs was similar to that of women with untreated hyperlipidaemia (1.8;
      95% confidence interval 0.9-3.4). We found no evidence for an increasing trend in
      breast cancer risk with increasing duration of statin use (median duration 1.8
      years, maximum 8.6 years).

PMID- 11986778
TI  - Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast
      cancer.
AB  - The early detection of breast cancer is the best means to minimise disease
      related mortality. Current screening techniques have limited sensitivity and
      specificity. Breast nipple aspirate fluid can be obtained noninvasively and
      contains proteins secreted from ductal and lobular epithelia. Nipple aspirate
      fluid proteins are breast specific and generally more concentrated than
      corresponding blood levels. Proteomic analysis of 1 microl of diluted nipple
      aspirate fluid over a 5-40 kDa range from 20 subjects with breast cancer and 13
      with nondiseased breasts identified five differentially expressed proteins. The
      most sensitive and specific proteins were 6500 and 15 940 Da, found in 75-84% of
      samples from women with cancer but in only 0-9% of samples from normal women.
      These findings suggest that (1) differential expression of nipple aspirate fluid
      proteins exists between women with normal and diseased breasts, and (2) analysis
      of these proteins may predict the presence of breast cancer.

PMID- 11986779
TI  - Increase in immune cell infiltration with progression of oral epithelium from
      hyperkeratosis to dysplasia and carcinoma.
AB  - In the present study, epithelium derived lesions of various pathological
      manifestations were examined histologically and immunohistochemically for
      mononuclear cell infiltration. The infiltrate under the transformed epithelium of
      oral lesions, was examined for differences in the composition of immune
      mononuclear cells as the epithelium moves from hyperkeratosis through various
      degrees of dysplasia to squamous cell carcinoma. The study was performed on 53
      human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine
      cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19
      cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as
      pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases).
      Immunohistochemical analysis of various surface markers of the tumour
      infiltrating immune cells was performed and correlated with the transformation
      level as defined by morphology and the expression of p53 in the epithelium. The
      results revealed that, in the tongue lesions, the changes in the epithelium from
      normal appearance to transformed were accompanied by a corresponding increase in
      the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most
      significant change was an increase in B lymphocytes in tongue lesions, that was
      in accordance with the transformation level (P<0.001). In the salivary gland, a
      significant number of cases did not show an infiltrate. In cases where an
      infiltrate was present, a similar pattern was observed and the more malignant
      tissues exhibited a higher degree of immune cell infiltration.

PMID- 11986780
TI  - Evaluation of HER-2/neu gene amplification and protein expression in non-small
      cell lung carcinomas.
AB  - HER-2/neu gene amplification and cell surface overexpression are important
      factors in breast cancer for prognosis and prediction of sensitivity to anti-HER
      2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of
      HER-2/neu expression is currently under evaluation. We investigated 238 non-small
      lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry
      using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%),
      including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of
      squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The
      association between protein expression and gene copy number per cell, as
      determined by fluorescence in situ hybridisation assay, was investigated in 51 of
      these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests.
      Marked (3+) protein expression and gene amplification were present in only 4% of
      samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy
      and did not result in high protein levels while in 7 (14%) the score 2+ was
      associated with maximum number of signals per cell <9. The prognostic implication
      of HER-2/neu protein expression was studied in 187 surgically resected tumours.
      No statistical difference in survival was observed comparing patients with
      positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a
      tendency to shorter survival. The therapeutic implications of protein expression
      and gene amplification in lung cancer need to be examined in prospective clinical
      trials.

PMID- 11986781
TI  - Human kallikrein gene 13 (KLK13) expression by quantitative RT-PCR: an
      independent indicator of favourable prognosis in breast cancer.
AB  - Kallikreins are a group of serine proteases with diverse physiological functions.
      KLK13 (previously known as KLK-L4) is a novel kallikrein gene located on
      chromosome 19q13.4 and shares a high degree of homology with other kallikrein
      family members. Many kallikrein genes were found to be differentially expressed
      in various malignancies, and their regulation is controlled by steroid hormones
      in prostate and breast cancer cell lines. We studied the expression of KLK13 by
      quantitative reverse transcriptase-polymerase chain reaction in 173 patients with
      epithelial breast carcinoma. An optimal cutoff point equal to the 40th percentile
      was defined, based on the ability of KLK13 to predict disease-free survival.
      KLK13 values were then associated with other established prognostic factors and
      with disease-free survival and overall survival. Higher positivity for KLK13
      expression was found in older, oestrogen receptor positive patients. In
      univariate analysis, KLK13 expression is a significant predictor of improved
      disease-free survival and overall survival (P<0.001 and P=0.009, respectively).
      Cox multivariate analysis indicated that KLK13 was an independent prognostic
      variable in the subgroups of patients with Grade I-II tumours and in patients who
      were oestrogen receptor and progesterone receptor positive, and node positive.
      Hazard ratios derived from Cox analysis, related to disease-free survival and
      overall survival were 0.22 (P=0.001) and 0.24 (P=0.008), respectively, for the
      Grade I-II group; 0.36 (P=0.008) and 0.44 (P=0.038), respectively, for the node
      positive group and 0.36 (P=0.008) and 0.18 (P=0.008), respectively, for the
      oestrogen receptor positive group. The adjusted hazard ratio for progesterone
      receptor positive patients for disease-free survival was 0.25 (P=0.012). For
      patients in the node positive and oestrogen receptor positive subgroup (n=51) the
      adjusted hazard ratio was 0.25 (P=0.006) and for the node positive and
      progesterone receptor positive subgroup (n=46) the hazard ratio was 0.24
      (P=0.008). Taken together, these data suggest that higher KLK13 expression in
      these subgroups of breast cancer patients is associated with an approximately 55
      to 80% reduction in the risk of relapse or death. We conclude that KLK13
      expression, as assessed by quantitative reverse transcriptase-polymerase chain
      reaction, is an independent favourable prognostic marker for breast carcinoma.

PMID- 11986782
TI  - Thymidine phosphorylase expression in normal, hyperplastic and neoplastic
      prostates: correlation with tumour associated macrophages, infiltrating
      lymphocytes, and angiogenesis.
AB  - Thymidine phosphorylase is an angiogenic factor primarily expressed by cancer
      cells, stromal cells and tumour-associated macrophages in many human
      malignancies. These different types of thymidine phosphorylase-expressing cells,
      however, may have a distinct place in the angiogenic process, and this question
      was addressed in the present study. A series of 20 normal/hyperplastic prostate
      glands and 60 prostate carcinomas was investigated by immunohistochemistry, using
      specific antibodies for thymidine phosphorylase (P-GF.44C), tumour-associated
      macrophages (CD68), endothelium (CD31) and prostate specific antigen (ER-PR8).
      Thymidine phosphorylase expression by normal and hyperplastic epithelial or
      stromal cells occurred almost exclusively in the context of an intense
      lymphocytic infiltrate. High thymidine phosphorylase cancer cells and thymidine
      phosphorylase stromal cells expression was associated with high angiogenesis in
      prostate carcinomas, and this significant association was extended to include
      both tumour-associated macrophages and tumour-infiltrating lymphocytes. Thymidine
      phosphorylase expression and tumour-infiltrating lymphocytes were related
      inversely with prostate specific antigen reactivity. In conclusion, thymidine
      phosphorylase is a major angiogenic factor in prostate carcinomas and its up
      regulation is likely to occur in the context of a host immune response.

PMID- 11986783
TI  - The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR-ABL positive
      chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic
      agents.
AB  - Chronic myeloid leukaemia is typically characterised by the presence of
      dysregulated BCR-ABL tyrosine kinase activity, which is central to the oncogenic
      feature of being resistant to a wide range of cytotoxic agents. We have
      investigated whether the inhibition of this tyrosine kinase by the novel compound
      STI571 (formerly CGP57148B) would render K562, KU812 cell lines and chronic
      myeloid leukaemia-progenitor cells sensitive to induction of cell kill.
      Proliferation assays showed STI571 to be an effective cytotoxic agent in chronic
      myeloid leukaemia-derived cell lines (IC(50) on day 5 of 4.6 microg ml(-1) and
      3.4 microg ml(-1) for K562 and KU812 respectively) and in leukaemic blast cells
      (per cent viability on day 3 at 4 microg ml(-1): 55.5+/-8.7 vs 96.4+/-3.7%).
      STI571 also appeared to specifically target bcr-abl expressing cells, as results
      from colony forming assays using the surviving cell fraction from STI571-treated
      peripheral CD34(+) chronic myeloid leukaemia blast cells, indicated a reduction
      in the expansion of colonies of myeloid lineage, but no effect on normal colony
      formation. Our data also showed synergy between STI571 and other anti-leukaemic
      agents; as an example, there were significant increases in per cent cell kill in
      cell lines cultured with both STI571 and etoposide compared to the two alone (per
      cent cell kill on day 3: 73.7+/-11.3 vs 44.5+/-8.7 and 17.8+/-7.0% in cultures
      with STI571 and etoposide alone respectively; P<0.001). This study confirms the
      central oncogenic role of BCR-ABL in the pathogenesis of chronic myeloid
      leukaemia, and highlights the role of targeting this tyrosine kinase as a useful
      tool in the clinical management of the disease.

PMID- 11986784
TI  - The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs
      membrane] localisation and induces cytochrome c release in breast cancer cells.
AB  - Bisphosphonates are well established in the management of cancer-induced bone
      disease. Recent studies have indicated that these compounds have direct
      inhibitory effects on cultured human breast cancer cells. Nitrogen-containing
      bisphosphonates including zoledronic acid have been shown to induce apoptosis
      associated with PARP cleavage and DNA fragmentation. The aim of this study was to
      identify the signalling pathways involved. Forced expression of the anti
      apoptotic protein bcl-2 attenuated bisphosphonate-induced loss of cell viability
      and induction of DNA fragmentation in MDA-MB-231 cells. Zoledronic acid-mediated
      apoptosis was associated with a time and dose-related release of mitochondrial
      cytochrome c into the cytosol in two cell lines. Rescue of cells by preincubation
      with a caspase-3 selective inhibitor and demonstration of pro-caspase-3 cleavage
      products by immunoblotting suggests that at least one of the caspases activated
      in response to zoledronic acid treatment is caspase-3. In both MDA-MB-231 and MCF
      7 breast cancer cells, zoledronic acid impaired membrane localisation of Ras
      indicating reduced prenylation of this protein. These observations demonstrate
      that zoledronic acid-mediated apoptosis is associated with cytochrome c release
      and consequent caspase activation. This process may be initiated by inhibition of
      the enzymes in the mevalonate pathway leading to impaired prenylation of key
      intracellular proteins including Ras.

PMID- 11986785
TI  - Rationale for combination therapy of chronic myelogenous leukaemia with imatinib
      and irradiation or alkylating agents: implications for pretransplant
      conditioning.
AB  - The tyrosine kinase activity of the BCR-ABL oncoprotein results in reduced
      apoptosis and thus prolongs survival of chronic myelogenous leukaemia cells. The
      tyrosine kinase inhibitor imatinib (formerly STI571) was reported to selectively
      suppress the proliferation of BCR-ABL-positive cells. Assuming that imatinib
      could be included in pretransplantation conditioning therapies, we tested whether
      combinations of imatinib and gamma-irradiation or alkylating agents such as
      busulfan or treosulfan would display synergistic activity in BCR-ABL-positive
      chronic myelogenous leukaemia BV173 and EM-3 cell lines. Further, primary cells
      of untreated chronic myelogenous leukaemia patients were assayed for colony
      forming ability under combination therapy with imatinib. Additionally, the
      cytotoxic effect of these combinations on BCR-ABL-negative cells was
      investigated. In the cell lines a tetrazolium based MTT assay was used to
      quantify growth inhibition after exposure to cytotoxic drugs alone or to
      combinations with imatinib. Irradiation was applied prior to exposure to
      imatinib. Interaction of drugs was analysed using the median-effect method of
      Chou and Talalay. The combination index was calculated according to the classic
      isobologram equation. The combination imatinib + gamma-irradiation proved to be
      significantly synergistic over a broad range of cell growth inhibition levels in
      both BCR-ABL-positive cell lines and produced the strongest reduction in primary
      chronic myelogenous leukaemia colony-forming progenitor cells. Combinations of
      imatinib + busulfan and imatinib + treosulfan showed merely additive to
      antagonistic effects. Imatinib did not potentiate the effects of irradiation or
      cytotoxic agents in BCR-ABL-negative cells. Our data provide the basis to further
      develop imatinib-containing conditioning therapies for stem cell transplantation
      in chronic myelogenous leukaemia.

PMID- 11986786
TI  - Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced
      by multidrug resistance-associated protein 1.
AB  - Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines,
      possibly increase colorectal cancer risk. Anthracyclines interfere with
      topoisomerase II, intercalate DNA and are substrates for P-glycoprotein and
      multidrug resistance-associated protein 1. P-glycoprotein and multidrug
      resistance-associated protein 1 protect colonic epithelial cells against
      xenobiotics. The aim of this study was to analyse the interference of anthranoids
      with these natural defence mechanisms and the direct cytotoxicity of anthranoids
      in cancer cell lines expressing these mechanisms in varying combinations. A
      cytotoxicity profile of rhein, aloe emodin and danthron was established in
      related cell lines exhibiting different levels of topoisomerases, multidrug
      resistance-associated protein 1 and P-glycoprotein. Interaction of rhein with
      multidrug resistance-associated protein 1 was studied by carboxy fluorescein
      efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic
      in the multidrug resistance-associated protein 1 overexpressing GLC4/ADR cell
      line compared to GLC4. Multidrug resistance-associated protein 1 inhibition with
      MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by
      rhein. No P-glycoprotein dependent rhein efflux was observed, nor was
      topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but
      did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR
      mechanisms. Rhein is a substrate for multidrug resistance-associated protein 1
      and induces apoptosis. It could therefore render the colonic epithelium sensitive
      to cytotoxic agents, apart from being toxic in itself.

PMID- 11986788
TI  - Cell cycle phase perturbations and apoptosis in tumour cells induced by aplidine.
AB  - Aplidine, dehydrodidemnin B, is a marine depsipeptide isolated from the
      Mediterranean tunicate Aplidium albicans currently in phase II clinical trial. In
      human Molt-4 leukaemia cells Aplidine was found to be cytotoxic at nanomolar
      concentrations and to induce both a G(1) arrest and a G(2) blockade. The drug
      induced cell cycle perturbations and subsequent cell death do not appear to be
      related to macromolecular synthesis (protein, RNA, DNA) since the effects occur
      at concentrations (e.g. 10 nM) in which macromolecule synthesis was not markedly
      affected. Ten nM Aplidine for 1 h inhibited ornithine decarboxylase activity,
      with a subsequently strong decrease in putrescine levels. This finding has
      questionable relevance since addition of putrescine did not significantly reduce
      the cell cycle perturbations or the cytotoxicity of Aplidine. The cell cycle
      perturbations caused by Aplidine were also not due to an effect on the cyclin
      dependent kinases. Although the mechanism of action of Aplidine is still unclear,
      the cell cycle phase perturbations and the rapid induction of apoptosis in Molt-4
      cells appear to be due to a mechanism different from that of known anticancer
      drugs.

PMID- 11986787
TI  - Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell
      responsiveness to topoisomerase inhibitor drugs.
AB  - Numerous studies demonstrate that the chemopreventive effect of non-steroidal
      anti-inflammatory drugs on colon cancer is mediated through inhibition of cell
      growth and induction of apoptosis. For these effects non-steroidal anti
      inflammatory drugs have been recently employed as sensitising agents in
      chemotherapy. We have shown previously that treatments with aspirin and NS-398, a
      cyclo-oxygenase-2 selective inhibitor, affect proliferation, differentiation and
      apoptosis of the human colon adenocarcinoma Caco-2 cells. In the present study,
      we have evaluated the effects of aspirin and NS-398 non-steroidal anti
      inflammatory drugs on sensitivity of Caco-2 cells to irinotecan (CPT 11) and
      etoposide (Vp-16) topoisomerase poisons. We find that aspirin co-treatment is
      able to prevent anticancer drug-induced toxicity, whereas NS-398 co-treatment
      poorly affects anticancer drug-induced apoptosis. These effects correlate with
      the different ability of aspirin and NS-398 to interfere with cell cycle during
      anticancer drug co-treatment. Furthermore, aspirin treatment is associated with
      an increase in bcl-2 expression, which persists in the presence of the anticancer
      drugs. Our data indicate that aspirin, but not NS-398, determines a cell cycle
      arrest associated with death suppression. This provides a plausible mechanism for
      the inhibition of apoptosis and increase in survival observed in anticancer drug
      and aspirin co-treatment.

PMID- 11986789
TI  - Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP
      kinase pathway status of tumour cells on the antiproliferative effect of ZD1839
      ("Iressa").
AB  - of ZD1839 ("Iressa") is an orally active, selective epidermal growth factor
      receptor-tyrosine kinase inhibitor (EGFR-TKI), which blocks signal transduction
      pathways implicated in proliferation and survival of cancer cells, and other host
      dependent processes promoting cancer growth. Permanent downstream activation of
      the mitogen-activated protein kinase pathway can theoretically bypass the
      upstream block of epidermal growth factor receptor-dependent mitogen-activated
      protein kinase activation at the epidermal growth factor receptor level. We
      investigated the impact of epidermal growth factor receptor content, p53 status
      and mitogen-activated protein kinase signalling status on ZD1839 sensitivity in a
      panel of human tumour cell lines: seven head and neck cancer cell lines and two
      colon cancer cell lines (LoVo, HT29) with derivatives differing only by a
      specific modification in p53 status (LoVo p53 wt + p53 mut cells, HT29 p53 mut +
      p53 wt rescued cells). The antiproliferative activity of ZD1839 was evaluated by
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. ZD1839
      concentrations ranged from 0.2-200 microM (48 h exposure). Epidermal growth
      factor receptor expression, p53 status and p42/p44 (for testing a constitutively
      active mitogen-activated protein kinase pathway status) were determined by
      competition analysis (Scatchard plots), denaturing gradient cell electrophoresis
      and Western blot, respectively. Epidermal growth factor receptor levels ranged
      from 388 to 33794 fmol mg(-1) protein, a range that is similar to that found in
      head and neck tumours. The IC(50) values for cell sensitivity to ZD1839 ranged
      from 6 to 31 microM and a significant inverse correlation (P=0.022, r=0.82)
      between IC(50) values and epidermal growth factor receptor levels was observed.
      There was no influence of p53 status on the sensitivity to ZD1839. In two head
      and neck cancer cell lines with comparably elevated epidermal growth factor
      receptor expression, a two-fold higher ZD1839 IC(50) value was found for the one
      with a constitutively active mitogen-activated protein kinase. In conclusion,
      ZD1839 was active against cells with a range of epidermal growth factor receptor
      levels, although more so in cells with higher epidermal growth factor receptor
      expression. Activity was unaffected by p53 status, but was reduced in cells
      strongly dependent on epidermal growth factor receptor signalling in the presence
      of an intrinsically activated mitogen-activated protein kinase pathway.

PMID- 11986790
TI  - Predictive values of sex and tumour site for survival benefit from 5FU in
      colorectal cancer.

PMID- 11986868
TI  - Genetic divergence and reproductive isolation in the Ochthebius (Calobius)
      complex (Coleoptera: Hydraenidae).
AB  - The reproductive isolation in hydrenid beetles of the Ochthebius complex was
      studied by analysing gene exchange in natural populations of O. quadricollis,
      Ochthebius sp. A and O. brevicollis steinbuehleri collected along the
      Mediterranean coasts. The ranges of these three species are largely allopatric,
      but sympatric areas were detected between contiguous taxa, ie, O. quadricollis
      and Ochthebius sp. A; Ochthebius sp. A and O. b. steinbuehleri. Three levels of
      reproductive isolation and genetic divergence were observed. One level involves
      extensive intraspecific genetic divergence within the biological species O.
      quadricollis, Ochthebius sp. A and O. brevicollis, associated with both physical
      barriers (eg, sea and sand stretches) and the low dispersal capacity of larvae
      and adults. The finding of transitional samples between the most differentiated
      population groups should indicate, however, that there is still some gene flow
      between the populations of the three taxa. Another level is found between
      Ochthebius sp. A and O. b. steinbuehleri, whose gene pools appear to be fairly
      distinct in spite of the fact that reproductive isolation is still incomplete: in
      their few syntopic sites, some F1 hybrids appeared indeed to have lower fitness,
      since backcrosses or recombinant genotypes were never observed. The final level
      in the evolution of reproductive isolation (full reproductive isolation) has been
      achieved by the species O. quadricollis and Ochthebius sp. A. No F1 or F(n)
      hybrids, nor backcrosses were found in their sympatric areas. The relative
      importance of ecological factors and evolutionary forces in the prevention of
      gene exchange between taxa are discussed.

PMID- 11986869
TI  - Ontogenetic reaction norm for binary traits: the timing of phallus development in
      the snail Bulinus truncatus.
AB  - The ontogenetic trajectory of plastic binary traits may provide valuable insights
      into their evolutionary rate of change. In this paper, the timing of the plastic
      response of a temperature-dependent sexual polymorphism, aphally, is investigated
      in the freshwater snail Bulinus truncatus. Aphally is defined as the loss of the
      male copulatory organ in otherwise hermaphroditic animals. Individuals from two
      inbred lines were switched at various times during their early development
      between 25 and 30 degrees C, and their phally status ascertained, in order to
      evaluate the parameters characterising the ontogenetic reaction norm of aphally
      to temperature. A series of nested models including parameters for the onset,
      offset, and the intensity of the response to temperature were fitted to the data,
      allowing for a wide range of reaction norms. One genotype did not show any
      variation in aphally ratio with switching temperature, while a switch-point model
      (onset and offset corresponding to the same developmental point in time) best
      fitted the second genotype. The results suggest that the plasticity of aphally is
      expressed before eggs hatch. Their consequences on the evolution of aphally are
      discussed. More generally, the methodology proposed here can be used to analyse
      variation in ontogenetic parameters of discrete traits.

PMID- 11986870
TI  - Characterisation of mildew resistant wheat-rye substitution lines and
      identification of an inverted chromosome by fluorescent in situ hybridisation.
AB  - Seven different mildew resistant wheat lines derived from crosses between
      triticale and bread wheat were examined by molecular cytogenetics and chromosome
      C-banding in order to determine their chromosomal composition. Genomic in situ
      hybridisation (GISH) showed the presence of rye germplasm in all the lines and
      identified three substitution lines, three double substitution lines and one
      addition-substitution line. C-banding identified rye chromosomes 1R and 4R in the
      addition-substitution line, rye chromosomes 1R and 6R in two substitution lines
      and 1R and 2R in the third line, and rye chromosome 1R in the three substitution
      lines. Two of the latter lines (7-102 and 7-169) contained a modified form of the
      chromosome; fluorescent in situ hybridisation (FISH) using five different
      repetitive DNA-probes showed a pericentric inversion of 1R in both lines. The
      breakpoints of the 1R inversion were between (1) the 5S rDNA site and the NOR
      region on the satellite of the short arm, and (2) between two AAC(5) sites close
      to the centromere on the long arm. The role of the rye chromosomes in the mildew
      resistance, the utilisation of the inverted 1R and the significance of the lines
      in wheat breeding are discussed.

PMID- 11986871
TI  - B-chromosomes and male-biased sex ratio with paternal inheritance in the fairy
      shrimp Branchipus schaefferi (Crustacea, Anostraca).
AB  - This study reports on male-biased sex ratios in west Mediterranean populations of
      the freshwater anostracan Branchipus schaefferi (Crustacea, Anostraca,
      Branchipodidae), in contrast to populations elsewhere. Crossing experiments over
      several generations indicate a clear paternal inheritance of the trait, possibly
      with a dosage effect. Various mechanisms which may underlie this phenomenon are
      discussed, the most plausible being the presence of one or more supernumerary
      ('B') chromosomes--as evidenced by karyological observations--interfering with
      sex determination and probably having an accumulation mechanism in male
      individuals.

PMID- 11986872
TI  - Infection polymorphism and cytoplasmic incompatibility in Hymenoptera-Wolbachia
      associations.
AB  - Most cases of Wolbachia infection so far documented in haplodiploid Hymenoptera
      are associated with parthenogenesis induction. Only three examples of Wolbachia
      mediated cytoplasmic incompatibility (CI) have been reported, resulting either in
      haploidisation of fertilised eggs, which develop into viable males, or in their
      death. To better document this variability, we studied two new Wolbachia-wasp
      associations involving Drosophila parasitoids. In Trichopria cf. drosophilae,
      individuals are infected by two different Wolbachia variants, populations are
      nearly totally infected, and Wolbachia induces incomplete CI resulting in death
      of the fertilised eggs. On the other hand, Pachycrepoideus dubius harbours only
      one bacterial variant, populations are polymorphic for infection, and Wolbachia
      has no detectable effect. These two cases show that the range of variation in
      Wolbachia's effects in Hymenoptera is as wide as in diploids, extending from
      complete CI to an undetectable effect. Cases so far studied show some parallel
      between the strength of incompatibility, the number of Wolbachia variants
      infecting each wasp, and the natural infection frequency. These empirical data
      support theoretical models predicting evolution of CI towards lower levels,
      resulting in the decline and ultimate loss of infection, and place multiple
      infections as being an important factor in the evolution of host-Wolbachia
      associations.

PMID- 11986873
TI  - Highly repeated DNA sequences in three species of the genus Pteropus
      (Megachiroptera, Mammalia).
AB  - Bat genomes are characterised by an A-T richness and by a small C-value compared
      with other mammalian groups. It has been suggested that the small C-value is
      mainly due to the lack of repetitive DNA sequences. However, little information
      about repetitive DNA sequences in this mammalian group is available at the
      molecular level. Here we describe a PstI family of repetitive DNA sequences
      present in three species of the genus Pteropus. These repetitive sequences are
      54.97% G-C rich, organised in tandem and with a unit length of 744 bp.
      Methylation analysis indicates that some of the CCGG target sites present in
      these repetitive DNA sequences have methylated cytosines and that there are small
      differences in the methylation pattern between species. Several features of this
      family of repetitive sequences suggest that they evolved by concerted evolution.

PMID- 11986874
TI  - Inbreeding and relatedness coefficients: what do they measure?
AB  - This paper reviews and discusses what is known about the relationship between
      identity in state, allele frequency, inbreeding coefficients, and identity by
      descent in various uses of these terms. Generic definitions of inbreeding
      coefficients are given, as ratios of differences of probabilities of identity in
      state. Then some of their properties are derived from an assumption in terms of
      differences between distributions of coalescence times of different genes. These
      inbreeding coefficients give an approximate measurement of how much higher the
      probability of recent coalescence is for some pair of genes relative to another
      pair. Such a measure is in general not equivalent to identity by descent; rather,
      it approximates a ratio of differences of probabilities of identity by descent.
      These results are contrasted with some other formulas relating identity, allele
      frequency, and inbreeding coefficients. Additional assumptions are necessary to
      obtain most of them, and some of these assumptions are not always correct, for
      example when there is localized dispersal. Therefore, definitions based on such
      formulas are not always well-formulated. By contrast, the generic definitions are
      both well-formulated and more broadly applicable.

PMID- 11986875
TI  - FISH mapping of 18S-28S and 5S ribosomal DNA, (GATA)n and (TTAGGG)n telomeric
      repeats in the periwinkle Melarhaphe neritoides (Prosobranchia, Gastropoda,
      Caenogastropoda).
AB  - Spermatocyte chromosomes of Melarhaphe neritoides (Mollusca, Prosobranchia,
      Caenogastropoda) were studied using fluorescent in situ hybridization (FISH) with
      four repetitive DNA probes (18S rDNA, 5S rDNA, (TTAGGG)n and (GATA)n). Single
      colour FISH consistently mapped one chromosome pair per spread using either 18S
      or 5S rDNA as probes. The telomeric sequence (TTAGGG)n hybridized with termini of
      all chromosomes whereas the (GATA)n probe did not label any areas. Simultaneous
      18S-5S rDNA and 18S-(TTAGGG)n FISH demonstrated that repeated units of the three
      multicopy families are closely associated on the same chromosome pair.

PMID- 11986876
TI  - Self-incompatibility in ryegrass 12. Genotyping and mapping the S and Z loci of
      Lolium perenne L.
AB  - Perennial ryegrass (Lolium perenne L.) is an outcrossing, wind-pollinated species
      exhibiting a gametophytic two-locus system of self-incompatibility (S and Z). The
      two incompatibility loci were genotyped in a cross between a doubled-haploid
      plant crossed as the female parent with a normal heterozygous plant. The S and Z
      loci were found to segregate in the expected 1:1 ratio and also segregated
      independently. The two loci were mapped to linkage groups one and two
      respectively, in accordance with the Triticeae consensus map. In addition, there
      were notable associations between the segregation of particular alleles mapping
      to the S locus region of linkage group 1 and those mapping to the WG889/CDO920
      loci region of linkage group 3 which resulted in significant segregation
      distortions. No such associations were found between the Z locus and this region
      or any other region of the genome. The L. perenne S and Z loci showed conserved
      synteny with the equivalent loci in rye (Secale cereale L.).

PMID- 11986877
TI  - Microsatellite data resolve phylogeographic patterns in European grayling,
      Thymallus thymallus, Salmonidae.
AB  - The phylogeography of an endangered salmonid, European grayling (Thymallus
      thymallus), was studied based on analysis of 17 nuclear microsatellite DNA loci.
      In agreement with earlier mitochondrial DNA (mtDNA) studies, phylogenetic
      relationships of the populations suggested that northern Europe was colonized
      from two distinct Pleistocene refugia. Furthermore, microsatellites revealed
      highly supported grouping of mainland Swedish, Norwegian, Danish, German and
      Slovenian populations, suggesting that grayling from the northwestern and central
      Europe have descended from their southern conspecifics. The level of divergence
      between populations was substantial, even across short geographical distances.
      Although this was in part due to postglacial colonization patterns and
      contemporary barriers for gene flow, the high divergence estimates between
      hydrologically connected sampling locations implied efficient interpopulation
      reproductive isolation. Microsatellites revealed that the populations exhibited,
      on average, only 3.5 (+/-2.2) alleles per locus, indicating that T. thymallus has
      strikingly low levels of intrapopulation genetic diversity as compared with other
      freshwater fish species. Accordingly, as indicated by analysis of molecular
      variance (AMOVA), only 49.1-58.0% of the total grayling microsatellite diversity
      resided within populations. A latitudinal genetic diversity gradient, potentially
      resulting from glaciation-mediated founder events, was not evident.
      Alternatively, it is possible that grayling display limited dispersal
      behaviour/capability, leading to low long-term effective population sizes and,
      consequently, depauperate intrapopulation polymorphism. These findings have
      implications for conservation of T. thymallus. Importantly, they exemplify that
      microsatellites can be highly informative for intraspecific phylogeography
      studies dealing with substantial divergence scales.

PMID- 11986881
TI  - Proceedings of the 3rd Congress of the Latin American Society of Hypertension.
      Caracas, Venezuela, 1-4 November 2000.

PMID- 11986878
TI  - Nuclear RFLP variation in Eucalyptus camaldulensis Dehnh. from northern
      Australia.
AB  - Eucalyptus camaldulensis Dehnh. is the most widely planted eucalypt in the
      tropics. Natural populations are riparian and sampling strategies for breeding
      programmes have assumed that gene flow among drainage basins is limited. RFLP
      variation, within and among 31 populations from river systems across northern
      Australia, was analysed to test this hypothesis. To allow comparisons within and
      between river systems, trees were sampled from up to three populations per river
      system. Allele frequencies were correlated with longitude for more than half the
      33 RFLP loci surveyed. Genetic identity was greatest between populations in
      closest geographic proximity, irrespective of river system, suggesting that
      sampling strategies for breeding programmes should be based on geographic
      distance rather than river system. The level of genetic variation was similar
      throughout the geographic range examined (mean H(E) = 0.49). However, there was
      evidence of a barrier to gene flow between populations in the east and west of
      the species range. The RFLP data support morphological evidence of hybridisation
      between E. camaldulensis and E. tereticornis Sm. in several populations in
      northeast Queensland and the genetic divergence of E. camaldulensis subsp.
      simulata Brooker and Kleinig.

PMID- 11986883
TI  - The epidemiology of hypertension in South America.
AB  - Although cardiovascular disease (CVD) is the leading cause of death and
      disability in the majority of the countries in Latin America we have few data
      about regional differences on this topic. Developing countries have scarce
      epidemiological data on cardiovascular (CV) risk factor prevalence and
      subsequently in their control and treatment. The load of the CV risk factors,
      especially hypertension, remains uncertain. The methodology of investigation
      varies from country to country and the criteria to define 'hypertension' is
      different according to the survey year. Data on CVD from USA and Europe have been
      extrapolated to our continent but recently two large epidemiological studies have
      been conducted in the southern region: FRICAS, primary prevention, and PRESEA,
      secondary prevention. The first pointed out the importance of each cardiovascular
      risk factor, including hypertension, in the development of acute myocardial
      infarction (AMI), and the second showed the poor control of them and the
      necessity to improve them.

PMID- 11986884
TI  - Hypertension in Brazil.
AB  - PREVALENCE: Mean values for prevalence of hypertension in 18 selected
      populations, varied between 15.7% (BP > or = 95 mm Hg) and 27.7% (BP > or = 90 mm
      Hg). In three Mall surveys in Salvador (n = 5093 volunteers), prevalence mean
      value was 33.7% (JNC VI criteria), being influenced by age (5.5 to 17.8% and 41.0
      to 54.9% for the 25-34 and 55-59 year old age groups, respectively) and
      socioeconomic class (24.7 and 39.6% for the highest and lowest social class,
      respectively, OR = 0.50 (0.26-0.95, P = 0.023). The national prevalence by the
      Ministry of Health is 20%. MORTALITY AND MORBIDITY: Mortality as a consequence of
      morbidity has increased, with stroke being a leading cause of death (11.3% of
      total deaths, 10.1% of all deaths in the 20-59 year-old age group, and 33.9% of
      cardiovascular deaths in Brazilian Capitals, 1994)Cardiovascular risk factors: At
      comparable age groups, prevalence of other major cardiovascular risk factors are:
      smoking approximately 27%, total cholesterol > or =200 mg/dl approximately 32.5%,
      glucose intolerance approximately 8.0%, diabetes approximately 7.5%, BMI 25-29
      approximately 29.1%, BMI > or = 30 approximately 9.6%, and physical inactivity
      approximately 92%. AWARENESS, TREATMENT, AND CONTROL: Data are very scarce. In
      the total Mall population (n = 4613) in Salvador, a high blood pressure was
      present in 24.4% of those who either denied hypertension or ignored blood
      pressure. Of those who reported to be hypertensives, only 34.5% had their blood
      pressure <140/90 mm Hg. In a national inquiry including 2519 physicians, 88%
      would start treatment with drug monotherapy, diuretics (53%), and angiotensin
      converting enzyme inhibitor (ACEI) (24%). If blood pressure control is not
      achieved, 55% will combine with another drug (diuretic + ACEI (46%) or + beta
      blocker (24%)), and 33% will increase the dosage. Nonpharmacological treatment
      would be prescribed for every patient by 17% of the physicians, while 62% would
      prescribe it for 25% of their patients. Adhesion is better for pharmacological
      (60%) than for nonpharmacological treatment (8%). FINAL REMARKS: Three Consensus
      Documents (the most recent in 1998), the creation of the Department of
      Hypertension Leagues, the Fighting Hypertension National Day, the Confederation
      of Hypertensive Patients Associations, and the very recent launch of the National
      Plan for Reorganization of Hypertension and Diabetes Care are some measures being
      taken in a joint effort of the Ministry of Health and the Brazilian Societies of
      Cardiology, Hypertension and Nephrology, to strengthen and improve the fight
      against hypertension.

PMID- 11986885
TI  - Hypertension in black people: pathophysiology and therapeutic aspects.
AB  - Salt sensitivity is regarded as an important contributor to the higher risk of
      hypertension in black people as compared with whites. This finding is in
      agreement with a better response to diuretics than to monotherapy with
      angiotensin-converting enzyme (ACE) inhibitor in black subjects. It is important
      to remember that the hypotensive effect of ACE inhibitor is augmented in patients
      on a thiazide diuretic. Moreover, the antihypertensive response to a specific
      drug varies among black patients. Thus, ACE inhibitors should also be viewed as
      important options to treat hypertensive black subjects. Results from clinical
      trials support an emphasis on lifestyle modification and a more intensive blood
      pressure lowering by pharmacological interventions to reduce the large black
      white gap in cardiovascular events and end-stage renal disease (ESRD) attributed
      to hypertension.

PMID- 11986886
TI  - Dopamine, hypertension and obesity.
AB  - Dopamine, a neurotransmitter, precursor of noradrenaline, is responsible for
      cardiovascular and renal actions, such as increase in myocardial contractility
      and cardiac output, without changes in heart rate, producing passive and active
      vasodilatation, diuresis and natriuresis. These cardiovascular and renal actions
      take place through the interaction with dopamine receptors, D(1), D(2), D(3),
      D(4), and D(5). Recent findings point to the possibility of D(6) and
      D(7)receptors. Dopamine is known to influence the control of arterial pressure by
      influencing the central and peripheral nervous system and target organs such as
      kidneys and adrenal glands, in some types of hypertension. Although dopamine and
      its derivatives have been shown to have antihypertensive effects, these are still
      being studied; therefore it is important to explain some physiological and
      pharmacological aspects of dopamine, its receptors, and the clinical uses it
      could have in the treatment of arterial hypertension and more recently in
      obesity, based on evidence proving a clear association between obesity and the
      decrease in the expression of D(2) receptors in the brain of obese persons.

PMID- 11986887
TI  - Hypertension and obesity.
AB  - Obesity, as defined by bodily weight (body weight) and by bodily conformation
      derived variables, accompanies hypertension in many patients. Both conditions are
      independent cardiovascular risk factors. In a formal survey carried out in the
      adult general population of Uruguay (LATIR Study, 575 adult and elderly subjects
      of whom 41.6% were males), we found the prevalence of hypertension to be 28.5%
      (95% CI: 24.9-32.4%) and that 74.4% of hypertensive individuals had a body mass
      index (BMI) higher than 25 kg/m(2) (95% CI: 67.0-80.8%). This association between
      obesity and hypertension forms part of a broader relationship between body weight
      and blood pressure (BP). In the general population, BP bears a positive linear
      correlation with BMI and waist-to-hip ratio over the continuous ranges of normal
      and unfavourable values of these three variables (r = 0.42, P < 0.001 for the
      correlation between BMI and mean BP, LATIR Study). Patients who present
      hypertension and obesity usually present other unfavourable conditions for
      cardiovascular prognosis, including changes in carbohydrate and lipid metabolism,
      hyperuricaemia, left ventricular hypertrophy, and/or the obstructive sleep apnoea
      syndrome. On average, hypertension is salt-sensitive in obese patients, and
      plasma volume and cardiac index are increased. Adequate control of body weight
      results in substantial reductions in total blood volume, cardiac output, BP and
      left ventricular mass, and in an amelioration or the disappearance of sleep
      apnoea. Adequate sodium intake restriction must form part of any diet prescribed
      to obese hypertensive patients. Various drug classes may be used to treat
      hypertension efficaciously in patients who also present obesity.

PMID- 11986888
TI  - Toward a new definition of atherosclerosis including hypertension: a proposal.
AB  - Atherosclerosis is a very complex disease and while research about its aetiology
      and development advances, it is more difficult to understand its pathology.
      Because of this atherosclerosis is not easy to define. Old and even new
      definitions are incomplete. Most of them do not take into consideration the
      endothelium on both sides, and some risk factors such as high blood pressure are
      ignored. Here we present a proposal for a redefinition of atherosclerosis and
      look forward to having a better understanding about the why and how of this
      lethal disease.

PMID- 11986889
TI  - Effects of LDL cholesterol on vascular function.
AB  - Oxidised low-density lipoprotein (LDL) cholesterol is vasoconstrictor, mitogenic,
      pro-inflammatory and thrombogenic. This review summarises the evidence for its
      vasoconstrictor properties. LDL cholesterol potentiates noradrenaline
      vasoconstriction in the peripheral vasculature, and in the coronary, cerebral and
      renal vascular beds. There is also blunting of endothelium-dependent vasodilator
      responses to acetylcholine. These effects are reversed, or at least reduced, by
      lipid-lowering agents and (because LDL cholesterol down-regulates endothelial
      nitric oxide synthase) by the administration of L-arginine, the substrate for
      nitric oxide (NO) formation. Anti-oxidants also improve endothelial function in
      hypercholesterolaemic animals and human patients. More research is needed to
      assess the possible beneficial effects of lipid lowering on vascular structure
      and function, and on cardiovascular morbidity and mortality, in
      normocholesterolaemic individuals.

PMID- 11986890
TI  - Role of endothelin in stress-induced hypertension.
AB  - In this study we investigated the role of endogenous endothelin in the
      cardiovascular response to acute stress, ie mild footshocks in conscious rats.
      Footshock-stress significantly increased mean arterial pressure and heart rate (P
      < 0.05). Peripheral or intracerebroventricular (IVT) administration of BQ 788, a
      selective antagonist of ET(B) receptor, did not alter pressor response to
      footshocks. Intraperitoneal injections of BQ 123 (1 mg/kg), a selective
      antagonist of the ET(A)-receptor, had a tendency to decrease, while BQ 123 (203
      ng/5 microl) IVT administration significantly reduced the pressor response to
      footshocks (-12 mm Hg, P < 0.001). Neither ET(A) nor ET(B) antagonists, when
      injected centrally or peripherally, altered basal blood pressure or heart rate.
      Our results may indicate a role of brain endothelin in the sympathetic mediated
      cardiovascular response to stress, via stimulation of ET(A) receptor.

PMID- 11986891
TI  - Endothelial dysfunction, angiotensin-converting enzyme inhibitors and calcium
      antagonists.
AB  - The endothelium plays a crucial role in the pathogenesis of cardiovascular
      disease. Endothelial function is attenuated by the presence of different well
      known cardiovascular risk factors. Evaluation of endothelial vasodilator function
      serve as an index integrating the overall stress imposed by cardiovascular risk
      factors and reinforce the suggestion that endothelial dysfunction is an early
      marker of cardiovascular disease that precedes clinical manifestations.
      Angiotensin-converting enzyme inhibitors have been shown to reduce the
      cardiovascular mortality, an effect that could be the consequence of an
      improvement in the endothelial function. Recent studies have shown that a calcium
      antagonist might improve the endothelial function, however, there is controversy
      about this action and also about the potential mechanisms for the effect of a
      calcium antagonist in the regulation of endothelial function.

PMID- 11986892
TI  - Large therapeutic studies in elderly patients with hypertension.
AB  - Hypertension, including isolated systolic hypertension, is one of the major risk
      factors for stroke and coronary heart disease in elderly subjects, and is a
      common antecedent of heart failure, because it increases the risk either directly
      through increased after-load or indirectly as a risk factor for acute myocardial
      infarction. The proportion of people aged 65 and above is increasing. It is well
      documented that hypertension treatment in elderly patients reduces cardiovascular
      morbidity and mortality more than could be expected from the results of trials in
      middle-aged subjects. Most of the trials on old and new antihypertensive drugs
      have yielded similar results. Nevertheless, evidence in subjects above 80 years
      of age is still limited. Hypertension (systolic-diastolic) and isolated systolic
      hypertension should be treated in elderly patients, starting with low doses of
      medication, particularly diuretics alone or in combination with beta-blockers or
      angiotensin-converting enzyme inhibitors. Isolated systolic hypertension could
      also be treated with a long-acting calcium antagonist starting with low doses.
      The large therapeutic studies, because of the limitations imposed upon
      conclusions by the selection and exclusion criteria, by the statistical
      techniques that established the trial designs and by other study-related
      constraints, cannot be applied to all elderly patients seen in daily practice.
      Specifically patients may differ in age, severity of illness, presence of
      morbidity and a myriad of other clinical nuances. Non-pharmacological measures
      such as lifestyle modifications (losing weight, limiting alcohol intake, reducing
      sodium intake and exercise), should be instituted or improved if they existed, to
      maximise the benefit and minimise the risk inherent in pharmacological treatment.
      A medical approach may reconcile the results of these large therapeutic studies
      with 'real life' quality of life and patients' preferences in order to improve
      treatment compliance.

PMID- 11986893
TI  - Isolated systolic hypertension: a new challenge in medicine.
AB  - In the elderly, isolated systolic hypertension (ISH) is a particularly good
      predictor of subsequent cardiovascular events. The purpose of this article is to
      review the evidence provided by the Systolic Hypertension Elderly Program (SHEP)
      and the Systolic Hypertension in Europe Study (Syst-Eur) on the benefits of
      lowering systolic blood pressure (SBP) and to report on the preliminary findings
      of the Maracaibo Aging Study (MAS) on ISH. These two trials, the SHEP using
      chlorthalidone and atenolol as step 2 and the Syst-Eur using nitrendipine and
      hydrochlorothyazide as step 2, demonstrated a decrease of more than 30% for all
      cardiovascular complications, including stroke and coronary events. MAS is a
      population-based study that included all the subjects older than 55 years of age
      that resided in a defined area of the city of Maracaibo. There was a high
      prevalence of ISH (45.7%) being higher among women than in men, and significantly
      increased with advancing age. SBP was associated with dementia when it was
      measured by an ambulatory blood pressure monitor (ABPM), while there was no
      association when it was assessed by the casual method. Diastolic blood pressure
      (DBP) as casual or measured by ABPM was not related to dementia. In conclusion,
      ISH is a serious public health problem and benefits from lowering elevated SBP to
      reduce the risk of cardiovascular events. It was shown there was a strong
      correlation between high SBP and cognitive dysfunction and this was best
      demonstrated by using ABPM. Research should address the impact of using modern
      diagnostic tools and to compare the efficacy of the different types of
      antihypertensive drugs.

PMID- 11986894
TI  - Salt intake, hypertension and diabetes mellitus.
AB  - Diabetes mellitus affects approximately 135 million people in the world. Diabetes
      and hypertension are both relatively common diseases in westernised countries.
      Both entities increase with age. Essential hypertension accounts for the majority
      of hypertension in people with type 2 diabetes, who constitute more than 90% of
      those with a dual diagnosis of diabetes and hypertension. The benefit conferred
      per mm Hg blood pressure reduction appears to be greater in persons with type 2
      diabetes than in those with hypertension and non-coexistent diabetes mellitus.
      Similar to a subset of patients with essential hypertension, type 2 diabetic
      patients manifest dietary NaCl-induced exacerbation of hypertension. Recent
      guidelines have emphasised that the target blood pressure levels for patients
      with diabetes should be lower than in other hypertensive groups. An increased
      total body sodium and enhanced vascular reactivity are found in people with
      diabetes and most type 2 diabetic patients are salt sensitive. Type 2 diabetes
      with hypertension is associated with reduced renal plasma flow when dietary salt
      intake is high. Experimental, observational and interventional evidence support
      the benefits of sodium restriction in hypertensives. However, the full effects of
      sodium restriction are usually not obvious for at least 5 weeks. Other favourable
      effects of moderate reduction in sodium intake are a regress left ventricular
      hypertrophy, decrease in diuretic-induced potassium wastage, reduction in
      proteinuria, protection against stroke and from osteoporosis and renal stones,
      and enhancement of the antihypertensive effect of the antihypertensive agents.

PMID- 11986895
TI  - Insulin resistance and upper-normal glucose levels in hypertension: a review.
AB  - Reduced insulin-mediated glucose disposal, indicative of insulin resistance, has
      been demonstrated in lean male hypertensives both with the hyperinsulinaemic
      euglycaemic clamp and the insulin suppression test. In lean hypertensives,
      insulin resistance was not accompanied by increases in fasting plasma insulin and
      glucose levels; but with modest hyperglycaemia and hyperinsulinaemia after a
      glucose load. Population studies (no stratification) reveal that: (1) insulin
      sensitivities vary widely in normotensives and hypertensives, (2) there are
      hypertensives and normotensives with similar degrees of insulin resistance, (3)
      not all hypertensives are insulin resistant, and (4) insulin resistance does not
      contribute to the blood pressure level of the hypertensive population. In large
      cross-sectional studies, the clustering of obesity, dyslipidaemia and type 2
      diabetes is largely responsible for the observed associations between insulin or
      insulin resistance and hypertension. Recent studies indicate a role of glucose in
      blood pressure control. Glucose has been shown to elevate blood pressure in the
      presence of endothelial dysfunction and glucose values in the upper-normal range
      have been shown to be associated with increased cardiovascular mortality. Since
      endothelial dysfunction is present in hypertensives, dyslipidaemic, obese and in
      glucose intolerant individuals, lowering of high-normal glucose levels becomes a
      new, additional therapeutic target in the management of these patients.
      Hyperglycaemia together with endothelial dysfunction may account for the
      increased incidence of hypertension in obesity and diabetes mellitus. Because of
      the strong association between insulin resistance, hyperglycaemia and endothelial
      dysfunction, and the clustering of risk factors in these subjects, we propose the
      lowering of high normal glucose levels as part of the therapeutic strategy to
      prevent cardiovascular and metabolic disease.

PMID- 11986896
TI  - Hypertension and diabetes.
AB  - Diabetes and hypertension will become increasingly common as the population
      becomes older and more obese. Together, they markedly increase cardiovascular and
      renal damage, placing all diabetic hypertensives at high risk. Fortunately, the
      appropriate use of lifestyle changes and multiple drugs will always slow and
      often stop the progression of this damage.

PMID- 11986897
TI  - Hypertension and coronary heart disease.
AB  - The association of hypertension and coronary heart disease is a frequent one.
      There are several pathophysiologic mechanisms which link both diseases.
      Hypertension induces endothelial dysfunction, exacerbates the atherosclerotic
      process and it contributes to make the atherosclerotic plaque more unstable. Left
      ventricular hypertrophy, which is the usual complication of hypertension,
      promotes a decrease of 'coronary reserve' and increases myocardial oxygen demand,
      both mechanisms contributing to myocardial ischaemia. From a clinical point of
      view hypertensive patients should have a complete evaluation of risk factors for
      atherosclerosis, damage of arterial territories other than the coronary one, and
      of the extension and severity of coronary artery involvement. It is important to
      emphasise that complications and mortality of patients suffering a myocardial
      infarction are greater in hypertensive patients. Treatment should be aimed to
      achieve optimal values of blood pressure, and all the strategies to treat
      coronary heart disease should be considered on an individual basis.

PMID- 11986898
TI  - The sympathetic nervous system: the muse of primary hypertension.
AB  - Von Euler characterised the sympathetic neurotransmitter noradrenaline (NA) and
      postulated that excessive neural tone was a cause of primary hypertension (PH).
      Thirty years ago, we found raised NA levels in 30-40% of young patients with PH.
      Laragh found plasma renin activity (PRA) a risk marker for coronary artery
      disease. With Esler, Miura, and Campese, a close association was found of plasma
      NA with PRA. We found raised tyrosine hydroxylase activity (AC) in the hearts of
      a rabbit model of sinoaortic denervated hypertension and in PH with raised plasma
      NA. Esler utilised titrated NA infusion and described increased spillover of NA
      from heart, kidney and subcortical areas of brain of patients with PH. With Eide
      we found raised cerebrospinal fluid (CSF) NA in PH (not secondary hypertension)
      and with Kolloch and Miura, we found raised plasma/CSF NA in conjunction with
      reduced dopaminergic tone. With Shkvatsabaya, Yurenev and Davison, we found that
      relaxation therapy improved the anger ambience and blood pressure of PH with
      raised plasma NA vs those with normal NA levels. Campese found a hypothalamic
      source of raised blood pressure in two rat models - microphenol treated and
      ischaemic kidney. The resulting hypertension was associated with raised NA
      turnover of their hypothalamic centres. Finally, with Hsueh and Hodis, we found
      raised plasma NA in association with insulin resistance increased left
      ventricular mass and intimal medial hypertrophy in Mexican-American diabetics and
      their yet unaffected offspring. Reliable estimates of human sympathetic AC,
      including levels of plasma NA in the effluent of selected organs and peripheral
      venous and arterial sites, may eventually be displaced by techniques using
      genetic analysis and molecular biology. Never the less, the sympathetic nervous
      system appears to play an important role in the pathogenesis, sequelae and
      therapy of PH.

PMID- 11986899
TI  - Ischaemic nephropathy: can we preserve renal function?
AB  - Atherosclerotic occlusive disease of the renal arteries or ischaemic nephropathy
      represents a frequent cause of progressive renal failure and is often amenable to
      therapy. Newer, non-invasive diagnostic studies are now available to identify
      patients with potentially correctable renovascular disease and avoid the risks of
      aortic cannulation or contrast nephrotoxicity. Before preceding with an
      intervention, careful assessment of the risks vs benefits of revascularisation
      are mandatory and intervention should be considered primarily for management of
      refractory hypertension or progressive renal dysfunction.

PMID- 11986900
TI  - Microalbuminuria in essential hypertension.
AB  - Microalbuminuria (urinary albumin excretion equal to 30-300 mg/24 h) is a
      reliable indicator of premature cardiovascular mortality in diabetic patients and
      in the general population. In insulin-dependent and non-insulin-dependent
      diabetes mellitus microalbuminuria is a marker of initial diabetic nephropathy
      and predicts the evolution toward renal insufficiency. In essential hypertension
      the clinical and prognostic role of microalbuminuria is more controversial. While
      it is a recognised marker of cardiovascular complications and a reliable
      predictor of ischaemic heart disease, its prognostic value on the risk of
      progressive renal alterations is still uncertain because no prospective studies,
      taking microalbuminuria as a selection criterion and renal insufficiency as an
      end point, are available. Blood pressure control with antihypertensive drugs is
      accompanied by a reduction in urinary albumin excretion. The favourable effects
      of antihypertensive agents on microalbuminuria appear to be proportional to blood
      pressure reduction, but angiotensin-converting enzyme inhibitors and angiotensin
      II-receptor antagonists show an additional beneficial effect on urinary albumin
      excretion. Whether the reduction of microalbuminuria obtained through
      pharmacological intervention has favourable prognostic implications remain to be
      demonstrated. However, screening for microalbuminuria is a relatively easy and
      inexpensive procedure and reveals a potentially treatable abnormality. Thus,
      considering that microalbuminuria identifies hypertensive subjects at higher risk
      than standard, urinary albumin excretion should be routinely measured in
      hypertensive patients and, in the presence of microalbuminuria, antihypertensive
      treatment should be intensified in order to obtain an optimal blood pressure
      control.

PMID- 11986901
TI  - Diuretics in the therapy of hypertension.
AB  - Antihypertensive monopharmacotherapy with diuretics renders blood pressure (BP)
      values under control in a large percentage of patients suffering from essential
      hypertension, and it reduces cardiovascular morbidity and mortality. Diuretics
      are effective in adult and elderly hypertensive subjects, independently of their
      race. Treatments with classic (high) doses of antihypertensive diuretics, such as
      25 mg hydrochlorothiazide once daily, raise the activity of the RAA system,
      decrease plasma potassium and magnesium concentrations, and cause untoward
      changes in carbohydrate metabolism and in the plasma lipid profile. These changes
      appear to limit the positive response of cardiovascular prognosis to
      antihypertensive therapy with classic doses of diuretics. Lower doses of
      diuretics reduce high BP to the sought extent in many patients, and they do not
      elicit or cause only mild unfavourable neuroendocrine and metabolic changes. When
      a low dose of an antihypertensive diuretic substance is used as
      monopharmacotherapy, it may take 12-14 weeks after the initiation of treatment
      for BP to attain final stable values. The following low-dose oral formulations of
      diuretics constitute effective once-daily monopharmacotherapies for mild-to
      moderate uncomplicated essential hypertension: bendrofluazide 1.25 mg,
      chlorthalidone 12.5 and 15 mg, cicletanine 50 mg, cyclopenthiazide 0.125 mg, HCTZ
      12.5 mg, and torasemide 2.5 and 5 mg. These formulations are safer than
      classically used high-dose formulations such as hydrochlorothiazide 25 and 50 mg.

PMID- 11986902
TI  - Angiotensin II supports sympathetically mediated vasopressor response to
      footshock-stress.
AB  - The present study was carried out to assess whether endogenous angiotensin II
      (Ang II) supports sympathetically mediated cardiovascular response to stress in
      conscious unrestrained rats, using experimental models in which the renin
      angiotensin-system was reduced or blocked. Footshock-stress increased mean
      arterial pressure (MAP) and heart rate (HR). Inhibition of angiotensin-converting
      enzyme with captopril or blockade of AT(1)angiotensin receptor with losartan,
      attenuated vasopressor responses to footshocks, while heart rate response was not
      altered. Bilateral nephrectomy suppressed vasopressor response as well the
      elevation of plasma noradrenaline and adrenaline induced by footshocks, and
      reduced heart rate response. Cardiovascular response to stress in nephrectomised
      rats was restored by exogenous administration of a subpressor dose of Ang II. Our
      results demonstrate that in conscious rats cardiovascular response to footshocks
      is dependent on an active renin-angiotensin system and they indicate that
      endogenous Ang II supports the sympathetically mediated vasopressor response to
      footshocks.

PMID- 11986903
TI  - Electrical activity of the heart and angiotensin-converting enzyme inhibitors on
      the hyperpolarising action of enalapril.
AB  - This paper describes the effect of angiotensin- converting enzyme (ACE)
      inhibitors on the electrical properties of the heart, particularly the effect of
      these drugs on heart cell coupling and impulse propagation and the possible
      implications for the generation of malignant ventricular arrhythmias. The
      hyperpolarising action of enalapril is described and evidence is presented that
      the activation of the sodium-potassium pump is involved in the increment in
      membrane potential elicited by the ACE inhibitor.

PMID- 11986904
TI  - Angiotensin II receptor antagonists role in arterial hypertension.
AB  - Angiotensin II receptor blockers represent a class of effective and well
      tolerated orally active antihypertensive drugs. Activation of AT(1) receptors
      leads to vasoconstriction, stimulation of the release of catecholamines and
      antidiuretic hormone and promote growth of vascular and cardiac muscle. AT(1)
      receptor blockers antagonise all those effects. Losartan was the first drug of
      this class marketed, shortly followed by valsartan, irbesartan, telmisartan,
      candesartan, eprosartan and others on current investigation. All these drugs have
      the common properties of blockading the AT(1) receptor thereby relaxing vascular
      smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce
      antihypertensive effect without modifying heart rate or cardiac output. Most of
      the AT(1) receptor blockers in use controlled blood pressure during the 24 h with
      a once-daily dose, without evidence of producing tolerance to the
      antihypertensive effect and being with low incidence of side effects even at long
      term use. Monotherapy in mild-to-moderate hypertension controls blood pressure in
      40 to 50% of these patients; when a low dose of thiazide diuretic is added, 60
      70% of patients are controlled. The efficacy is similar to angiotensin-converting
      enzyme (ACE) inhibitors, diuretics, calcium antagonists and beta-blocking agents.
      AT(1) receptor blockers are specially indicated in patients with hypertension who
      are being treated with ACE inhibitors and developed side effects such as, cough
      or angioedema. The final position in the antihypertensive therapy in this special
      population and other clinical situations, such as left ventricular hypertrophy,
      heart failure, diabetes mellitus and renal disease, has to be determined in large
      prospective clinical trials, some of which are now being conducted and seem
      promising.

PMID- 11986905
TI  - Blockade of endothelial enzymes: new therapeutic targets.
AB  - Nitric oxide (NO) is the principal vasoactive substance produced by the vascular
      endothelium with antitrombotic, antiatherogenic and vasodilator actions. The loss
      of these functions is now known as endothelial dysfunction (ED) and it has been
      proposed that it is the final common pathway in cardiovascular disease. At the
      moment there is an important body of evidence that supports the proposal that ED
      is a consequence of an imbalance between the free radicals, NO, superoxide (O(
      )(2)) and peroxynitrate (ONOO(-)). This imbalance is the result of the actions of
      well known risk factors associated with an inappropriate diet and infection
      inflammation. Angiotensin-converting enzyme (ACE) inhibitors are highly effective
      against a variety of cardiovascular disorders. Experimental and clinical studies
      have demonstrated a beneficial effect of ACE inhibition on endothelial function.
      This action is mainly due to an increase in the concentration of bradykinin,
      which stimulates NO production. ACE inhibitors also block the formation of
      angiotensin II that results in a lower production of O(-)(2). These effects lead
      to improve the imbalance between NO and O(-)(2) observed in cardiovascular
      disease. This proposal is supported by different clinical trials that have shown
      that the ACE inhibitors with higher affinity by the tissular ACE, such as
      quinapril, are the most effective in reversing ED principally by accumulating
      bradykinin. Recently, the HOPE study conducted in patients at a high risk of
      cardiovascular events, showed how ramipril, an ACE inhibitor with high affinity
      by tissular ACE, decreased the mortality rate due to cardiovascular disease
      independently of changes in blood pressure.

PMID- 11986906
TI  - Diuretics in the treatment of patients who present congestive heart failure and
      hypertension.
AB  - The main operational objective of diuretic therapy in patients who present
      congestive heart failure and hypertension is to reduce or to suppress excess
      bodily fluid. Effective diuretic therapy decreases cardiac size when the heart is
      dilated, and it reduces lung congestion and excess water. Consequently, external
      respiratory work diminishes and cardiac output would be redistributed in favour
      of systemic vascular beds other than that of the respiratory muscles; dyspnoea
      decreases markedly and there is a slight reduction in fatigue. This clinical
      improvement and the fall in body weight caused by diuretics entail an increase in
      effort capacity. Subsequent exercise training ameliorates the abnormal
      ventilatory response to physical effort and the skeletal muscle myopathy that
      occur in heart failure, and thereby it attenuates dyspnoea and decreases fatigue
      further. Loop and/or thiazide-type diuretics may be used to augment natriuresis
      in patients with congestive heart failure and hypertension. The state of renal
      function, the existence of certain co-morbid conditions, potential untoward drug
      actions, and possible interactions of diuretics with nutrients and with other
      drugs are some of the factors that must be considered at the time of deciding on
      the diuretic drug(s) and dose(s) to be prescribed. Spironolactone has been found
      to increase life expectancy and to reduce hospitalisation frequency when added to
      the conventional therapeutic regimen of patients with advanced congestive heart
      failure and systolic dysfunction. Therefore, spironolactone should be the drug of
      choice to oppose the kaliuretic effect of a loop or of a thiazide-type diuretic.

PMID- 11986907
TI  - Update on the use of calcium antagonists on hypertension.
AB  - Calcium antagonists represent an important group of drugs for the treatment of
      hypertension; they are effective in the whole range of severity of the disease.
      Dihy- dropyridine derivatives are most frequently used, and can be used in
      association with other antihypertensive drugs; meanwhile phenylalkylamines and
      benzothiazepines are contraindicated in association with beta-blocker drugs.
      Calcium antagonists with slow starting effect and long duration of action are the
      choice for use in long-term antihypertensive treatment. This group of drugs is
      specially indicated in elderly patients, in those with diabetes mellitus and in
      patients with coronary heart disease. Phenylalkylamines and benzothiazepine
      derivatives are also used in patients with supraventricular arrhythmias. This
      group of agents is as safe as diuretics, angiotensin-converting enzyme-inhibitors
      and beta-blocking drugs in the long-term treatment of hypertension.

PMID- 11986908
TI  - Sympatholytic therapy in primary hypertension: a user friendly role for the
      future.
AB  - Effective therapy (Rx) in primary hypertension (PH) for 50 years, has featured
      sympathetic nervous system (SNS) mechanisms. Ganglionic blockers and reserpine
      were pre-eminent in the 1940s (mydriasis, ileus, impotence, peptic ulcer).
      Guanethidine, and in the 1960s clonidine and methyldopa, were step II agents to
      thiazide Rx in the 1950s. Reserpine depletes brain (depression) and peripheral
      (PPH) noradrenaline (NA) storage sites, guanethidine depleted NA storage via
      blockade of reuptake. Venomotor sympathoplegia resulted in postural hypertension.
      An analogue, metaiodobenzyguandine is used in diagnosis and Rx of
      pheochromocytoma. Clonidine lowers both central and PPH neuronal NA release via
      both stimulation of alpha agonist adrenoreceptors (sedation) and specific
      imadazoline binding sites (IBS). Methyldopa lowers pressure via PPH induced NA
      release (retrograde ejaculation) and via alphamethyl NA on central alpha-2
      receptors (depression). The alpha-2 and alpha-2 receptor antagonists (alphaRA)
      cause reflex tachycardia and first-dose hypotension. Recently a two-fold
      incidence of congestive heart failure after alphaRA in treated primary
      hypertensives question their role in PH. The beta RA, with or absent alphaRA,
      remain premier since the 1970s due to mortality benefit in systolic dysfunction
      and post myocardial infarction, certifying the role of the SNS in the
      pathogenesis and sequelae and Rx of PH. The future includes beta RA, specific IBS
      agents, angiotensin (AII) RA with avid presynaptic AII affinity and vasopeptidase
      inhibitiors that raise peptides and suppress SNS.

PMID- 11986909
TI  - New strategies for blood pressure control.
AB  - EDUCATIONAL OBJECTIVES: (1) understand the evidence-based data regarding blood
      pressure (BP) control; (2) review the current short-fall in hypertension control
      efforts; (3) appreciate physicians' attitudes toward aggressive BP therapy; (4)
      review the newer clinical trial evidence in support of treatment to lower BP
      goals.

PMID- 11986910
TI  - Higher urinary albumin excretion is associated with abnormal erythrocyte
      Na(+)/Li(+) countertransport (SLC) in non-modulating essential hypertensives and
      offspring of hypertensive parents.
AB  - Non-modulating is a highly reproducible type of sodium-sensitive hypertension.
      The aim of this study was to evaluate in non-modulating individuals the
      erythrocyte sodium-lithium countertransport (SLC) abnormalities, which have been
      mentioned as a marker of non-modulation, and the association with increased
      microalbuminuria, as a marker of an early kidney impairment. We measured
      erythrocyte SLC in 10 normotensives (NT, 28 +/- 4 years), 20 offspring of
      hypertensive parents being 10 modulating (MHO, 25 +/- 6 years) and 10 non
      modulating (NMHO, 26 +/- 5 years), and 23 essential hypertensives being 12
      modulating (MHT, 34 +/- 5 years) and 11 non-modulating (NMHT, 32 +/- 4 years). In
      all the subjects studied, microalbuminuria was determined by duplicate 24-h urine
      collection by radioimmunoassay. In non-modulating offspring of hypertensive
      parents and essential hypertensives. SLC was significantly elevated when compared
      either with normotensives without family history of hypertension, modulating
      offspring of hypertensive parents or essential hypertensives (P < 0.025).
      Likewise, 24-h urinary albumin excretion was found higher in non-modulating
      individuals (essential hypertensives and offspring of hypertensive parents) than
      in modulating individuals (P < 0.01). In conclusion, non-modulators with higher
      SLC countertransport sodium transport abnormalities showed higher elimination of
      microalbuminuria suggesting that non-modulators may have an increased risk for
      developing cardiovascular morbidity and kidney impairment even in normotensive
      subjects with familiarity history of hypertension.

PMID- 11986911
TI  - Differential blood pressure effects of oral glucose and intravenous L-arginine in
      healthy lean normotensive and obese hypertensive subjects.
AB  - We investigated the role of insulin and glucose in the pathophysiology of
      hypertension associated with obesity. The comparative effects of an oral glucose
      load and of an L-arginine infusion on plasma glucose, plasma insulin and blood
      pressures (BP) were assessed in lean normotensive and in obese hypertensive
      males. Oral glucose (75 g in 1-2 min) induced a small but significant lowering of
      BP in lean normotensives, but failed to modify BP in obese hypertensives. L
      arginine infusion (30 min, 500 mg/kg total dose) reduced BP; significantly
      greater reductions in systolic and diastolic BP were observed in obese
      hypertensives than in the control group. Both oral glucose and L-arginine induced
      greater increases in plasma insulin in obese hypertensives than in lean
      normotensives. Endothelial dysfunction which accompanies the insulin resistant
      state of obesity, glucose intolerance and hypertension, may account for the
      different BP effects induced by glucose and L-arginine in obese hypertensives and
      lean normotensives.

PMID- 11986912
TI  - Clustering of silent cardiovascular risk factors in apparently healthy Hispanics.
AB  - Ischaemic heart disease is one of the leading causes of cardiovascular morbidity
      and mortality. Because most factors leading to cardiovascular disease have a
      silent course, early screening is needed for prevention and for halting disease
      progression. In our centre, a programme was implemented in apparently healthy
      subjects for the early diagnosis and treatment of factors known to increment the
      risk of developing cardiovascular and metabolic disease. We present data from the
      first 153 individuals evaluated. The incidence of modifiable risk factors in our
      healthy population was as follows: overweight 33% (BMI: 25-30 kg/m(2)), obesity
      45% (BMI >30 kg/m(2)), sedentarism 84%, arterial hypertension 15% (>140/90 mm
      Hg), hyperinsulinaemia 50%, glucose intolerance 14% (>160 mg/dl 120 min after 75
      g glucose load), type 2 diabetes mellitus 5%, hypercholesterolaemia 50%,
      hypertriglyceridaemia 28%, and salt sensitivity 25%. Clustering of three or more
      cardiovascular risk factors was observed in 59% of the apparently healthy
      subjects. Obesity was associated with greater clustering of risk factors. The
      cardiovascular dysmetabolic syndrome was present in 72% of the obese individuals.
      These findings revealed a very high prevalence of cardiovascular risk factors in
      apparently healthy Hispanics. Even though these individuals were clinically
      asymptomatic, they are at increased risk for developing cardiovascular disease
      and type 2 diabetes mellitus. Mechanisms for the early detection and correction
      of modifiable risk factors in the healthy population must be implemented. Only
      through prevention will a reduction in the incidence of cardiovascular
      atherosclerotic disease and of type 2 diabetes mellitus be achieved.

PMID- 11986913
TI  - Comparison of two nimodipine formulations in healthy volunteers.
AB  - The objective of this study was to assess the pharmacokientic parameters of
      regular nimodipine (Bayer), 30 mg, given every 6 h and nimodipine AP (nimodipine
      in micro particles with programmed action contained in tablets, developed by
      Biocontrolled-Leti Group Laboratories), 120 mg, given every 24 h. Subjects (19
      healthy volunteers, five female; 14 male: age: 21 +/- 0.7 years) received one
      formulation over 5 days. Then, after a washout period of 7 days, the other
      formulation was given. The analyst was blinded to the relationship in formulation
      received. Antecubital blood samples were taken before the first tablet was taken
      and after 15, 45, 60 min and 2, 4, 6, 8, 12, 13, 18 and 24 h on day 1 and five of
      each formulation. Nimodipine blood levels were analysed by HPLC. At steady-state
      regular nimodipine reached a C-max of 10.208 +/- 0.317 ng/ml, at a t-max of 1 h;
      minimum concentration 6 h after dosage was 1.2929 +/- 0.411 ng/ml, half-life was
      estimated in 2.9 h. Meanwhile nimodipine AP 120 mg reach a C-max of 11.885 +/-
      0.403 ng/ml; a t-max of 1 h with a minimum concentration 24 h after the last dose
      of 4.2387 +/- 0.353 ng/ml (P < 0.001). Apparent half-life was calculated in 17.8
      h (P < 0.001). Area under the curve for the 24 h period was 143.76 ng/ml/min for
      regular nimodipine and 183.7 ng/ml/min for nimodipine AP 120 mg (P < 0.001),
      indicating better bioavailability. In conclusion nimodipine in AP formulation 120
      mg produced similar peak plasma levels (C-max) than regular nimodipine, but with
      higher trough (C-min) values and stable plasma levels with one administration
      every 24 h. This formulation would be more suitable when nimodipine chronic
      therapy is indicated.

PMID- 11986914
TI  - Insulin resistance and hypertension in postmenopausal women.
AB  - The aim of the study was to elucidate the role of hyperinsulinaemia/insulin
      resistance in hypertension of lean postmenopausal women. Twenty-four women with
      essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass
      index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who
      had been without treatment for a 4-week washout period, and 10 normotensive
      postmenopausal weight- and aged-matched controls were compared. Both groups were
      not receiving hormone replacement therapy. Hip and waist circumferences were
      measured and waist/hip ratios were calculated. Casual blood pressure was measured
      in triplicate. Neither the fasting plasma glucose nor serum insulin levels in
      hypertensive women and normotensives differed significantly. During 2 h oral
      glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5
      +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs.
      112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17
      mg/dl) were significantly higher in hypertensives than that for normotensives (P
      < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive
      women were significantly higher than that in normotensives after 15 min (92.04 +/
      59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45
      microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean
      serum insulin: plasma glucose ratio for hypertensive women was significantly
      higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/-
      0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min
      (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three
      comparisons). Significant correlations were observed between the daytime period
      and 24-h average ambulatory systolic blood pressure and the area under the serum
      insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher
      fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels
      did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic
      index was higher in dippers than in non-dippers. We conclude that in lean,
      postmenopausal hypertensive women insulin resistance is increased compared with
      age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates
      with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be
      involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

PMID- 11986915
TI  - Blood pressure response in 24 hours in patients with high blood pressure treated
      with two nifedipine formulations once a day.
AB  - A double-blind, comparative and prospective study with nifedipine once a day was
      undertaken, in patients with mild and moderate high blood pressure. Blood
      pressure was measured by mercury sphygmomanometer in two positions: resting and
      sitting at 3, 6 and 12 weeks of treatment and by ambulatory blood pressure
      monitoring (ABPM) over 24 h; both were carried out before and after the treatment
      and the uniformity in the pressure levels were obtained by means of the
      Smoothness Index. Fifty-four patients were included in the trial, 28 in the
      microgranules group and 26 in the osmotic pump group. These groups were similar
      at the baseline in age, gender, weight, height, diastolic and systolic blood
      pressure. The nifedipine microgranules group had a heart rate higher than the
      nifedipine osmotic pump group at baseline (X(M) = 75.58 vs. X(B) = 70.75). Blood
      pressure decreased significantly during the first 3 weeks; 85% in the
      microgranules group and 75% in the osmotic pump group reached a blood pressure <
      or =140/90 mm Hg at the end of the study. Three patients in the microgranules
      group and two in the osmotic pump group required an additional antihypertensive
      drug. In both groups, the average blood pressure over 24 h was lowered without
      differences between groups. A decrease was induced in the heart rate in both
      groups which reached a marginal statistical significance in the microgranules
      nifedipine group. No changes were induced in the laboratory tests; two patients
      in the microgranules (8%) nifedipine group and five in the nifedipine osmotic
      pump group, adverse effects were observed, of which only one in each group
      required stopping the treatment.

PMID- 11986916
TI  - Efficacy and safety of two different formulations of nifedipine (GITS) vs. slow
      release microgranules in patients with mild and moderate hypertension.
AB  - The objective of this study was to compare the safety and efficacy of nifedipine
      in two different formulations (osmotic pump and slow release microgranules) in
      patients with essential hypertension. A total of 91 patients with mild and
      moderate essential hypertension were recruited in a randomised, double-blinded
      trial, to receive a daily dose of 30 mg of nifedipine GITS or nifedipine slow
      release microgranules for 8 weeks. Patients who did not respond to the above
      mentioned dose at week 4 of treatment received an increased dose of 60 mg per day
      of either drug for the remaining trial period. The primary end point of this
      study was the variation in mean sitting diastolic blood pressure (SDBP) from
      baseline values to the ones found at week 4 of treatment. The secondary end point
      was the variation in mean sitting systolic blood pressure (SSBP). Drug
      tolerability was measured according to incidence of side effects. The results
      were that both presentations reduced the mean SDBP and SSBP with similar
      efficacy. Drug side effects were also similar in both formulations. In conclusion
      nifedipine in slow release microgranules (NMG) is as effective as osmotic pump
      nifedipine (GITS) in reducing blood pressure with a similar tolerability profile.

PMID- 11986918
TI  - Purification and characterization of maltooligosaccharide-forming amylase from
      Bacillus circulans GRS 313.
AB  - A maltooligosaccharide-forming amylase that hydrolyzes starch into maltotriose
      and maltopentaose was found in the culture filtrate of a strain of Bacillus
      circulans GRS 313 isolated from local soil. The enzyme was purified by organic
      solvent fractionation, Sephadex G-100 gel filtration and CM-Sephadex column
      chromatography. Optimum pH and temperature of amylase were evaluated using
      response surface methodology (RSM) and were found to be 48 degrees C and 4.9,
      respectively. The enzyme was stable up to 60 degrees C and its pH stability was
      in the range of 5.0-8.0. The Km and Vmax of the amylase with starch were 11.66
      mg/ml and 68.97 U, respectively, and the energy of activation, Ea, was 7.52
      kcal/mol. Dextrin inhibited the enzyme competitively, with a Ki of 6.1 mg/ml, and
      glucose caused noncompetitive inhibition with a Ki of 9.5 mg/ml. The enzyme was
      inhibited by Hg2+, Mn2+, Fe3+ and Cu2+ and enhanced by Co2+ and Mg2+. EDTA
      reversed the inhibitory effect of the metals. Paper chromatographic and high
      performance liquid chromatography analysis of the products of the amylolytic
      reaction showed the presence of maltotriose, maltotetraose, maltopentaose,
      maltose and glucose in the starch hydrolysate.

PMID- 11986919
TI  - Biodecolourization of azo and triphenylmethane dyes by Dichomitus squalens and
      Phlebia spp.
AB  - Nine white-rot fungal strains were screened for biodecolourization of brilliant
      green, cresol red, crystal violet, congo red and orange II. Dichomitus squalens,
      Phlebia fascicularia and P. floridensis decolourized all of the dyes on solid
      agar medium and possessed better decolourization ability than Phanerochaete
      chrysosporium when tested in nitrogen-limited broth medium.

PMID- 11986920
TI  - The performance of fungal xylan-degrading enzyme preparations in elemental
      chlorine-free bleaching for Eucalyptus pulp.
AB  - Cellulase-free xylan-degrading enzyme preparations from Acrophialophora nainiana,
      Humicola grisea var. thermoidea and two Trichoderma harzianum strains were used
      as bleaching agents for Eucalyptus kraft pulp, prior to a chlorine dioxide and
      alkaline bleaching sequence. In comparison to the control sequence (performed
      without xylanase pretreatment), the sequence incorporating enzyme treatment was
      more effective. Removal of residual lignin was indicated by a reduction in kappa
      number. Overall, enzyme preparations from T. harzianum were marginally more
      effective in reducing pulp viscosity and chlorine chemical consumption and
      improving the brightness of the kraft pulp. However, the highest reduction in
      pulp viscosity was mediated by the xylanase preparation from A. nainiana.
      Xylanase pretreatment compares very favorably with that of chemical pulping.

PMID- 11986921
TI  - Solubilization of low-rank coal by Trichoderma atroviride: evidence for the
      involvement of hydrolytic and oxidative enzymes by using 14C-labelled lignite.
AB  - The deuteromycete Trichoderma atroviride is able to solubilize lignite in
      dependence on a given carbon source for growth. When cultivated on media
      containing glutamate, this mold excreted a set of different enzymes with
      hydrolytic activity. Addition of lignite to the growth media induced the
      synthesis of extracellular lignite-specific esterase activity but no evidence has
      been provided for its direct involvement in the process of lignite
      solubilization. Hence, the basic capability of T. atroviride enzymes to degrade a
      variety of ester and ether bonds at the surface or within the bulky lignite
      structure was tested using coal following its direct labelling with 14C-alkyl
      iodide. The participation of hydrolytic and oxidative enzymes in lignite
      degradation was assessed by measuring the release of 14C radioactivity from
      selectively alkylated carboxylic and phenolic OH groups. T. atroviride cleaved
      both carboxylic esters using esterases and the phenolic ether bonds by using
      oxidative enzymes, most likely laccases.

PMID- 11986922
TI  - An implementation of the HACCP system in the production of food-packaging
      material.
AB  - The Hazard Analysis Critical Control Point (HACCP) system according to the Codex
      Alimentarius model was applied to the processes of five paper and paperboard
      mills and four plants further converting paper or board intended for contact with
      foodstuffs. The generalised flow diagrams of the processes are presented. Each of
      the overall processes contained 40-150 process steps. Normally three to five
      sessions with HACCP teams and additional private negotiations were needed for
      each mill or plant. Hazards leading to critical control points (CCPs) were
      microbiological (handling/storage, circulation water, starch, process
      environment) and physical (process environment) in mills, and microbiological
      (storage, lacquers or glues, packaging and process environment), chemical
      (printing) and physical (storage of products, packaging and process environment)
      in plants. Specifications, critical limits (e.g., based on different kinds of
      reports and instructions), monitoring methods (microbiological and visual) and
      frequency, responsibilities and corrective actions of the processes are
      presented. Most of the improvements focused on improving the process environment.
      In five cases, hygiene training was included in the implementation of the HACCP
      system.

PMID- 11986923
TI  - Inactivation of a transcriptional repressor during empirical improvement of the
      tylosin producer, Streptomyces fradiae.
AB  - Remarkably few changes of significance seem to have occurred within the tylosin
      biosynthetic gene cluster of Streptomyces fradiae during an extensive portion of
      the empirical strain improvement programme carried out at Lilly Research
      Laboratories over many years. None of the promoters for polyketide synthase (PKS)
      genes or for regulatory elements changed within this part of the lineage, nor
      were any mutations detected in other tyl promoters, although the full set was
      probably not analysed. Of five regulatory genes within the tyl cluster, only tylQ
      was altered, having undergone a single point mutation that inactivated its
      product (a transcriptional repressor). Also unchanged was a gene with unassigned
      function. Since point mutations affecting antibiotic-biosynthetic enzymes are
      unlikely to have played a major role in empirical strain improvement, enhanced
      tylosin production levels appear to have resulted, in large measure, from
      uncharacterized mutations occurring outside the tyl cluster.

PMID- 11986924
TI  - Potential microbiological hazards in the production of refined paper products for
      food applications.
AB  - This study sought to investigate the significance of raw materials (starch-based
      glues, raw material papers) at different microbiologically critical stages in the
      manufacturing process of refined paper products. The study examined the
      occurrence of microorganisms in the process and in end-product samples.
      Microbiological surveys verified that the production and use of pasteurized
      starch-based glue was the most important factor threatening the process hygiene
      and product safety. Subsequently, the production and use of starch-based glue was
      changed, and a follow-up programme targeting the microbiological quality of glue
      was developed as part of a hygiene and safety management system. A total of 33
      spore-forming bacterial and 15 enterobacterial isolates were ribotyped, and 22
      and 10 different ribogroups (ribotypes), respectively, were generated. These
      isolates from starch-based glue, raw material paper and end products were
      atypical and, thus, in many cases physiological, chemotaxonomic (FAME) and
      molecular (partial 16S rDNA) results did not correspond. The most common spore
      forming bacteria (55% of the isolates) were Paenibacillus sp. and within this
      genus several new species were also proposed. The most common enterobacteria
      (87%) were Enterobacter cloacae and Citrobacter freundii belonging to bacteria in
      hazard group 2, or species closely related to them. It was demonstrated that the
      same spore-forming bacteria (ribotypes) were present in both the glue samples and
      the end products (45% of isolates). All RiboPrint patterns were saved at the VTT
      identification library for future use.

PMID- 11986925
TI  - Production, recovery and immunogenicity of the protective antigen from a
      recombinant strain of Bacillus anthracis.
AB  - The protective antigen (PA) is one of the three components of the anthrax toxin.
      It is a secreted nontoxic protein with a molecular weight of 83 kDa and is the
      major component of the currently licensed human vaccine for anthrax. Due to
      limitations found in the existing vaccine formulation, it has been proposed that
      genetically modified PA may be more effective as a vaccine. The expression and
      the stability of two recombinant PA (rPA) variants, PA-SNKE-deltaFF-E308D and PA
      N657A, were studied. These proteins were expressed in the nonsporogenic avirulent
      strain BH445. Initial results indicated that PA-SNKE-deltaFF-E308D, which lacks
      two proteolysis-sensitive sites, is more stable than PA-N657A. Process
      development was conducted to establish an efficient production and purification
      process for PA-SNKE-deltaFF-E308D. pH, media composition, growth strategy and
      protease inhibitors composition were analyzed. The production process chosen was
      based on batch growth of B. anthracis using tryptone and yeast extract as the
      only source of carbon, pH control at 7.5, and antifoam 289. Optimal harvest time
      was 14-18 h after inoculation, and EDTA (5 mM) was added upon harvest for
      proteolysis control. Recovery of the rPA was performed by expanded-bed adsorption
      (EBA) on a hydrophobic interaction chromatography (HIC) resin, eliminating the
      need for centrifugation, microfiltration and diafiltration. The EBA step was
      followed by ion exchange and gel filtration. rPA yields before and after
      purification were 130 and 90 mg/l, respectively. The purified rPA, without
      further treatment, treated with small amounts of formalin or adsorbed on alum,
      induced, high levels of IgG anti-PA with neutralization activities.

PMID- 11986926
TI  - Purification and characterization of recombinant malate synthase enzymes from
      Streptomyces coelicolor A3(2) and S. clavuligerus NRRL3585.
AB  - Malate synthases (MS) from Streptomyces coelicolor A3(2) and S. clavuligerus
      NRRL3585 were cloned by polymerase chain reaction into a glutathione S
      transferase (GST) fusion expression vector and heterologously expressed in
      Escherichia coli. The fusion GST-MS construct improved the soluble expression of
      MS by approximately 10-fold compared to the soluble expression of nonfusion MS.
      With the significant improvement in levels of soluble MS, purification and
      subsequent cleavage of recombinant MS from GST were facilitated in this study.
      Using purified enzymes, optimized parameters, which achieved maximal specific
      activity, were established in the enzymatic assay for streptomycete MS. The
      average purified specific activities of S. coelicolor and S. clavuligerus MS were
      26199 and 11821 nmol/mg min, respectively. Furthermore, enzymatic analysis
      revealed that the two streptomycete MS displayed a similar Km value for acetyl
      CoA, but S. coelicolor MS had a Km value for glyoxylate that is approximately
      sixfold higher than S. clavuligerus MS.

PMID- 11986927
TI  - Comparison of microporous and nonporous membrane bioreactor systems for the
      treatment of BTEX in vapor streams.
AB  - Increased regulatory constraints on industrial releases of atmospheric volatile
      organic compounds (VOCs) have resulted in an interest in using biofilters,
      bioscrubbers and air/liquid membranes for treatment of vapor phase waste streams.
      In this report, we describe the comparison of the use of two fundamentally
      different types of membrane module systems that allow the rapid diffusion of
      vapor phase aromatics and oxygen to an active biofilm for subsequent
      biodegradation. One system used a commercial membrane module containing
      microporous polypropylene fibers while the other used a nonporous silicone tubing
      membrane module for the delivery of substrate (a mixture of benzene,
      ethylbenzene, toluene, and xylenes [BTEX]) and electron acceptor (O(2)). Tests of
      the systems under similar conditions with BTEX in the vapor feed stream showed
      significant performance advantages for the silicone membrane system. The average
      surface-area-based BTEX removal rate for the microporous membrane system over 500
      h of operation was 7.88 microg h(-1) cm(-2) while the rate for the silicone
      membrane system was 23.87 microg h(-1) cm(-2). The percentages of BTEX removal
      were also consistently better in the silicone membrane system versus the
      microporous system. Part of the performance problem associated with the
      microporous membrane system appeared to be internal water condensation and
      possible plugging of the pores with biomass over time that could not be resolved
      with vapor phase backflushing.

PMID- 11986928
TI  - Biodegradation of a crude oil by three microbial consortia of different origins
      and metabolic capabilities.
AB  - Microbial consortia were obtained three by sequential enrichment using different
      oil products. Consortium F1AA was obtained on a heavily saturated fraction of a
      degraded crude oil; consortium TD, by enrichment on diesel and consortium AM, on
      a mixture of five polycyclic aromatic hydrocarbons [PAHs]. The three consortia
      were incubated with a crude oil in order to elucidate their metabolic
      capabilities and to investigate possible differences in the biodegradation of
      these complex hydrocarbon mixtures in relation to their origin. The efficiency of
      the three consortia in removing the saturated fraction was 60% (F1AA), 48% (TD)
      and 34% (AM), depending on the carbon sources used in the enrichment procedures.
      Consortia F1AA and TD removed 100% of n-alkanes and branched alkanes, whereas
      with consortium AM, 91% of branched alkanes remained. Efficiency on the
      polyaromatic fraction was 19% (AM), 11% (TD) and 7% (F1AA). The increase in
      aromaticity of the polyaromatic fraction during degradation of the crude oil by
      consortium F1AA suggested that this consortium metabolized the aromatic compounds
      primarily by oxidation of the alkylic chains. The 500-fold amplification of the
      inocula from the consortia by subculturing in rich media, necessary for use of
      the consortia in bioremediation experiments, showed no significant decrease in
      their degradation capability.

PMID- 11986929
TI  - The effects of temperature on the aerobic stability of wheat and corn silages.
AB  - The aim of this work was to study the effects of temperature on the aerobic
      stability of wheat and corn silages. Three silage samples from each crop were
      taken from the faces of six different commercial bunker silos immediately after
      unloading them. The samples were exposed to air for 3 or 6 days at 10, 20, 30 or
      40 degrees C. The most intensive deterioration occurred at 30 degrees C. Samples
      incubated at 30 degrees C had the highest yeast counts, most prolific CO(2)
      production and greatest increases in pH. Silage samples exposed to 10 or 40
      degrees C remained stable. The duration of exposure had a significant effect on
      aerobic stability, especially at 30 degrees C. Temperature has a significant
      effect on silage aerobic stability. In a warm climate, special care should be
      taken during unloading of silage in order to prevent intensive aerobic
      deterioration.

PMID- 11986930
TI  - Cell surface hydrophobicity and mycolic acid composition of Rhodococcus strains
      isolated from activated sludge foam.
AB  - The bacteria causing foaming in activated sludge plants are considered to be
      hydrophobic, and their hydrophobicity is assumed to be a crucial factor in their
      foam-forming ability. This study showed no consistent relationship between cell
      surface hydrophobicity (CSH), as determined by microbial adherence to
      hydrocarbons, of three Rhodococcus spp. isolated from activated sludge foam and
      their ability to produce a stable foam. There also appeared to be no correlation
      between the mycolic acid composition of these strains, in terms of chain length
      or degree of unsaturation, and either CSH or foaming ability. Zeolite and
      bentonite successfully prevented foaming by a Rhodococcus sp. in pure culture,
      which suggests that cell surface charge may also play a role in foam
      stabilisation.

PMID- 11986931
TI  - Structure and on-site formation of biofilms in paper machine water flow.
AB  - Paper machine biofilms formed in situ on stainless steel surfaces were studied. A
      robust flow cell was fitted to side stream (1.8 m s(-1)) of the spray water
      circuit of a paper machine. This on-site tool allowed for assessing the efficacy
      of antifoulants and the adequacy of steel polishing under mill conditions. A
      rapid fluorescence-based assay was developed to quantify the biomass of shallow
      biofilms on machine steel. The fluorescence matched the ATP content measured for
      the same biofilms. Electrolytic polishing reduced the tendency of biofouling of
      500 grit surface steel. Biofilm grew under machine conditions as clusters on the
      steels, showing uniformly coccoid, filaments or short rods; only one cell type in
      each cluster. The biofilm clusters excluded latex beads of 0.02 microm with
      hydrophilic or with hydrophobic surfaces from penetrating more than three to four
      layers of cells. Under the high hydraulic flow at the machine (1.8 m s(-1)), the
      biofilm grew in 7 days 6-10 microm thick. The high flow rate guided the shape of
      the biofilm clusters emerging after the primary attachment of cells. Adhered
      individual bacteria were the platform on steel to which solids such as paper
      machine fines then accumulated.

PMID- 11986932
TI  - Production of testosterone from phytosterol using a single-step microbial
      transformation by a mutant of Mycobacterium sp.
AB  - A testosterone (TS)-producing mutant, ST2, was derived from a phytosterol
      assimilating and androst-4-ene-3,17-dione (AD)-producing bacterium, Mycobacterium
      sp. B-3805S, using nitrosoguanidine (NTG) mutagenesis. Production of TS from
      phytosterol using a single-step microbial transformation process by ST2 was
      investigated in a 5-l surface-aeration microprocessor-controlled fermentor loaded
      with a synthetic medium supplemented with 0.1% phytosterol, 2% glucose and 1%
      peptone at 30 degrees C. An increase in dissolved oxygen at the initial stage of
      fermentation favored the side-chain degradation of phytosterol to AD. Later in
      the fermentation, a decrease in the dissolved oxygen to zero resulted in a
      decrease in pH to 6.0 as well as the reduction of AD to TS. Under optimal
      fermentation conditions, the maximum conversion ratio of phytosterol to TS was
      31% after 120 h cultivation. It was concluded that the control of dissolved
      oxygen in the fermentation culture is the most important parameter for production
      of TS from phytosterol via AD. TS was isolated from the fermentation culture by
      addition of Amberlite XAD-7 resin and was further purified by flash
      chromatography on a silica gel column. After crystallization, TS was obtained as
      needle crystals with the correct melting point.

PMID- 11986933
TI  - Physiological and molecular detection of crystalliferous Bacillus thuringiensis
      strains from habitats in the South Central United States.
AB  - Gram-positive, endospore-forming Bacillus thuringiensis-like strains were
      isolated from 95 of 413 samples collected at the 0-5 cm depth of noncultivated
      soils and stagnant or dried-up ponds as well as from dust from stored grain
      products in South Central United States. Based on the production of parasporal
      crystals, 25 isolates were identified as B. thuringiensis after examining 227 B.
      thuringiensis-like colonies. The greatest proportion of samples yielding B.
      thuringiensis were from the dust from grain storage. The sodium acetate selective
      medium, heat processing, and crystal staining used in the initial screening
      revealed diverse populations of B. thuringiensis, which were categorized into
      distinct crystal morphological groups. Sugar fermentation, antibiotic
      sensitivity, growth characteristics and PCR studies showed diversity among the
      isolates that were distributed among 25 of the 58 known strains. The most
      frequently isolated strains were kurstaki, aizawai, morrisoni, thuringiensis,
      sotto and kenyae that together represented more than 90% of the characterized
      isolates. PCR analysis using 30 family primer pairs for cry and cyt genes showed
      that the frequency of the cry1 gene (62%) was predominant followed by the cry2
      genes (30%), and the rest (8%) were other cry gene types, such as cry3, cry4,
      cry10, cry11, cry14, cry15, cry20, cry24 and cry26. Both cyt1 and -2 genes were
      also detected. Several isolates showed PCR products on the gel that were not
      consistent with the expected sizes of nucleotides targeted by the primers. These
      were suggestive of nonspecific amplifications and were not used in the
      characterization process.

PMID- 11986934
TI  - Effect of process parameters on the production and drying of Leuconostoc
      mesenteroides cultures.
AB  - Leuconostoc mesenteroides BLAC was grown on MRS broth or on a carrot juice
      medium, and the effects of sugar concentration, type of pH control, aeration and
      fermentor size on viable counts were examined. The effect on viability of the
      type of centrifuge used to concentrate the bacterial culture was also examined.
      When the MRS broth had the traditional 110 mM glucose, pH control did not
      increase the final population. However, using a zone pH control mode, increasing
      the glucose content of MRS both from 110 to 220 mM almost doubled the population.
      In MRS broth, the amount of acetic acid produced was the same for all treatments,
      and was proportional to the amount of citrate consumed. There was a significantly
      lower cell yield in the carrot juice medium when the pH was not regulated. In the
      carrot juice medium, pH had a more pronounced effect on the final population
      level than did aeration, even though the quantity of viable cells was greater
      when the culture was aerated. In MRS broth, glucose was completely consumed
      during fermentation, but this was not the case in carrot juice medium. Aeration
      resulted in increased acetic acid content of the fermented medium. Viable counts
      were not affected by scaling the volume of the fermentation from 2 to 15 l,or by
      the type of centrifuge used to concentrate the cells. Cells were concentrated by
      a factor of 10, but in both centrifuge types, viable counts showed only an
      eightfold average increase. However, freeze-dried powders obtained from the
      continuous pilot-plant-centrifuged cultures had, on the average, 33% lower
      populations than those obtained from the laboratory unit.

PMID- 11986935
TI  - Enhanced production of heterologous macrolide aglycones by fed-batch cultivation
      of Streptomyces coelicolor.
AB  - A media development program for the enhanced production of macrolide aglycones by
      Streptomyces coelicolor is described. Shake flask studies utilizing a yeast
      extract and a bakers' yeast increased production by 200% and 80%, respectively.
      However, ammonia generation and high pH were identified as potential problems in
      these enriched media. Studies in pH-controlled fermentors revealed that
      production stage pH significantly affects macrolide titers, with low pH (5.5)
      being more productive than high pH (6.5). Implementation of glucose feeding in
      shake flask cultures reduced ammonia generation and controlled production stage
      pH, resulting in significantly enhanced productivities. The combined effects of
      media supplementation and glucose feeding resulted in a three to five-fold
      overall improvement in total macrolide aglycone titers, and is the first reported
      high-level (>1 g/l) production of recombinant polyketides in a heterologous host.

PMID- 11986936
TI  - Centrosome replication, genomic instability and cancer.
AB  - Karyotypic alterations, including whole chromosome loss or gain, ploidy changes,
      and a variety of chromosome aberrations are common in cancer cells. If
      proliferating cells fail to coordinate centrosome duplication with DNA
      replication, this will inevitably lead to a change in ploidy, and the formation
      of monopolar or multipolar spindles will generally provoke abnormal segregation
      of chromosomes. Indeed, it has long been recognized that errors in the centrosome
      duplication cycle may be an important cause of aneuploidy and thus contribute to
      cancer formation. This view has recently received fresh impetus with the
      description of supernumerary centrosomes in almost all solid human tumors. As the
      primary microtubule organizing center of most eukaryotic cells, the centrosome
      assures symmetry and bipolarity of the cell division process, a function that is
      essential for accurate chromosome segregation. In addition, a growing body of
      evidence indicates that centrosomes might be important for initiating S phase and
      completing cytokinesis. Centrosomes undergo duplication precisely once before
      cell division. Recent reports have revealed that this process is linked to the
      cell division cycle via cyclin-dependent kinase (cdk) 2 activity that couples
      centriole duplication to the onset of DNA replication at the G(1)/S phase
      transition. Alterations in G(1)/S phase regulating proteins like the
      retinoblastoma protein, cyclins D and E, cdk4 and 6, cdk inhibitors p16(INK4A)
      and p15(INK4B), and p53 are among the most frequent aberrations observed in human
      malignancies. These alterations might not only lead to unrestrained
      proliferation, but also cause karyotypic instability by uncontrolled centrosome
      replication. Since several excellent reports on cell cycle regulation and cancer
      have been published, this review will focus on the role of centrosomes in cell
      cycle progression, as well as causes and consequences of aberrant centrosome
      replication in human neoplasias.

PMID- 11986937
TI  - Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid
      leukaemia of infancy: report from the MRC Childhood Leukaemia working party.
AB  - The clinical features, cytogenetics and response to treatment have been examined
      in 180 infants (aged <1 year) with acute leukaemia; 118 with acute lymphoblastic
      leukaemia (ALL) and 62 with acute myeloid leukaemia (AML). Comparison of clinical
      features showed no difference in age or sex distribution between infants with ALL
      and AML but infants with ALL tended to have higher leucocyte counts at
      presentation. Cytogenetic abnormalities involving 11q23 were found in 66% of ALL
      and 35% of AML cases, the commonest, t(4;11) being found only in ALL. The other
      recognised 11q23 translocations were found in both types of leukaemia. Few
      patients had the common cytogenetic abnormalities associated with ALL in older
      children and few with AML had good risk abnormalities. Four year event-free
      survival 60% cf 30% (P = 0.001) and survival 65% cf 41% (P = 0.007) were
      significantly better in AML than ALL. These results were due to a lower risk of
      relapse 27% cf 62% at four years. Superior event-free survival was also seen in
      the subgroup of patients with 11q23 abnormalities and AML (55% cf 23%). The
      reasons for superior response in AML are unknown but may be related to the
      intensity of treatment, lineage of the leukaemia or other as yet unidentified
      factors.

PMID- 11986938
TI  - Functional disturbance of marrow stromal microenvironment in the myelodysplastic
      syndromes.
AB  - The potential contribution of abnormal marrow stromal function to ineffective
      haemopoiesis in the myelodysplastic syndromes is unclear. We have compared the
      ability of stromal layers from normal (n = 7) and myelodysplastic (n = 9) marrow
      to alter proliferation and survival of the granulocyte-macrophage colony
      stimulating factor/interleukin-3-dependent cell line F-36P. Co-cultures for 72 h
      in the absence of exogenous cytokines were either in direct contact with stroma
      or separated by transwell inserts. On normal stromal layers, the ratio of
      adherent F-36P cells relative to stromal cells increased from a mean of 0.2 +/-
      0.01 (s.d.) at 4 h of co-culture to 0.34 +/- 0.08 after 72 h (n = 7).
      Corresponding values on myelodysplastic stroma (0.2 +/- 0.02 at 4 h and 0.35 +/-
      0.05 at 72 h; n = 9) indicated that the ability of myelodysplastic stromal layers
      to regulate short-term proliferation of F-36P cells may be similar to normal.
      Apoptosis of F-36P cells was quantified after co-culture with normal or
      myelodysplastic stroma: results from myelodysplastic co-cultures were
      standardized as a fraction of values from co-cultures with paired normal stroma
      (apoptotic ratio). Augmented apoptosis of F-36P cells was detected in 8/9 co
      cultures with myelodysplastic stroma (mean = 15.7 +/- 9.7%, n = 9), compared with
      corresponding normal stroma (mean = 12.4 +/- 4.6%, n = 7, P < 0.05) with a mean
      apoptotic ratio of 1.4 +/- 0.5 (P < 0.05). There was no correlation between
      stroma-related apoptosis and FAB type, tumour necrosis factor-alpha
      concentrations in the culture supernatant or numbers of stromal macrophages, and
      no evidence of involvement of the Fas pathway. Increased apoptosis was detected
      in cells grown in transwell inserts over stroma (23.8 +/- 3%, n = 5) compared to
      adherent cells in cultures with normal stromal layers, but this survival
      difference was not observed in co-cultures with myelodysplastic stroma. These
      results suggest that abnormal stromal function in patients with myelodysplastic
      syndromes may contribute to increased apoptosis of haemopoietic cells within the
      marrow microenvironment. The effect appears to be dependent on close cellular
      contact, rather than the release of soluble factors, but the exact mechanism
      remains unclear.

PMID- 11986939
TI  - Production of matrix metalloproteinase-9 in early stage B-CLL: suppression by
      interferons.
AB  - Besides vascular endothelial growth factor (VEGF) and basic fibroblast growth
      factor (bFGF), matrix metalloproteinases (MMPs) play critical roles in
      angiogenesis, tumor invasion and metastasis. Increased angiogenesis is observed
      in chronic B lymphocytic leukemia (B-CLL) and published data reported VEGF and
      bFGF production in this disease. The purpose of this study was to investigate MMP
      expression in early stage B-CLL. Elevated MMP-9 concentrations were detected by
      ELISA in the sera of B-CLL patients (median level 250 ng/ml) compared with
      healthy donors (67 ng/ml) (P < 0.0001), and immunostaining with antibodies
      against MMP-9 and B cell antigens (CD19, CD23) substantiated the presence of MMP
      9 in tumoral B lymphocytes. By using RT-PCR, ELISA and zymography experiments, we
      confirmed that B-CLL cells expressed and released the pro-form of MMP-9 with Mr
      92 kDa (158-1300 pg/ml/10(6) cells/48 h), p-aminophenylmercuric acetate
      generating a 82 kDa active form. In contrast, the production of MMP-9 by normal
      counterpart B cells was significantly low (28-169 pg/ml/10(6)cells/48 h).
      Moreover, B-CLL culture supernatants contained bFGF (median levels 17 pg/ml/10(6)
      cells/48 h), VEGF (1.4 pg/ml/10(6) cells/48 h) and TNF-alpha (0.2 pg/ml/10(6)
      cells/48 h). TNF-alpha and VEGF antibodies blocked MMP-9 at the mRNA and protein
      levels. Interferons (IFNs) type I or type II repressed MMP-9 gelatinolytic
      activity in a dose and time dependency, and this was reflected by a parallel
      inhibition of MMP-9 mRNA and protein. IFNs however did not affect the production
      of bFGF, VEGF and TNF-alpha. Together, our data show that B-CLL lymphocytes
      synthesize MMP-9 and emphasize the specific inhibitory actions of IFNs on its
      expression.

PMID- 11986940
TI  - Role for c-jun N-terminal kinase in treatment-refractory acute myeloid leukemia
      (AML): signaling to multidrug-efflux and hyperproliferation.
AB  - A relationship was proved between constitutive activity of leukemic cell c-jun-N
      terminal kinase (JNK) and treatment failure in AML. Specifically, early treatment
      failure was predicted by the presence of constitutive JNK activity. The
      mechanistic origins of this association was sought. A multidrug resistant
      leukemic cell line, HL-60/ADR, characterized by hyperexpression of c-jun and JNK
      activity, was transfected with a mutant c-jun vector, whose substrate N-terminal
      c-jun serines were mutated. Down-regulated expression occurred of c-jun/AP-1
      dependent genes, catalase and glutathione-S-transferase (GST) pi, which
      participate in cellular homeostasis to oxidative stress and xenobiotic exposure.
      MRP-efflux was abrogated in HL-60/ADR cells with dominant-negative c-jun, perhaps
      because MRP1 protein expression was also lost. Heightened sensitivity to
      daunorubicin resulted in cells subjected to this change. Biochemical analysis in
      67 primary adult AML samples established a statistical correlation between
      cellular expression of c-jun and JNK activity, JNK activity with
      hyperleukocytosis at presentation of disease, and with exuberant MRP efflux.
      These findings reflect the survival role for c-jun/AP-1 and its regulatory kinase
      previously demonstrated for yeast in homeostatic response to oxidative stress and
      in operation of ATP-binding cassette efflux pumps, and may support evolutionary
      conservation of such function. Thus, JNK and c-jun may be salient drug targets in
      multidrug resistant AML.

PMID- 11986941
TI  - Reduced effect of gemtuzumab ozogamicin (CMA-676) on P-glycoprotein and/or CD34
      positive leukemia cells and its restoration by multidrug resistance modifiers.
AB  - Gemtuzumab ozogamicin (CMA-676), a calicheamicin-conjugated humanized anti-CD33
      mouse monoclonal antibody, has recently been introduced clinically as a promising
      drug for the treatment of patients with acute myeloid leukemia (AML), more than
      90% of which express CD33 antigen. However, our recent study suggested that CMA
      676 was excreted by a multi- drug-resistance (MDR) mechanism in P-glycoprotein (P
      gp)-expressing leukemia cell lines. We analyzed the in vitro effects of CMA-676
      on leukemia cells from 27 AML patients in relation to the amount of P-gp, MDR
      associated protein 1 (MRP1), CD33 and CD34, using a multi-laser-equipped flow
      cytometer. The cytocidal effect of CMA-676, estimated by the amount of
      hypodiploid portion on cell cycle, was inversely related to the amount of P-gp
      estimated by MRK16 monoclonal antibody (P = 0.004), and to the P-gp function
      assessed by intracellular rhodamine-123 accumulation in the presence of PSC833 or
      MS209 as a MDR modifier (P = 0.0004 and P = 0.002, respectively). In addition,
      these MDR modifiers reversed CMA-676 resistance in P-gp-expressing CD33(+)
      leukemia cells (P = 0.001 with PSC833 and P = 0.0007 with MS209). In CD33(+) AML
      cells from 13 patients, CMA-676 was less effective on CD33(+)CD34(+) than
      CD33(+)CD34(-) cells (P = 0.002). PSC833 partially restored the effect of CMA-676
      in CD33(+)CD34(+) cells. These results suggest that the combined use of CMA-676
      and a MDR modifier will be more effective on CD33(+) AML with P-gp-related MDR.

PMID- 11986942
TI  - Dexrazoxane has no impact on sensitivity of childhood leukemic blasts to
      daunorubicin.
AB  - Dexrazoxane (DEX) prevents the formation of free radical, lipid peroxidation and
      cardiotoxicity caused by anthracyclines. Due to a concern about its possible
      interference with anthracyclin cytotoxicity, the in vitro effect of DEX on
      daunorubicin (DNR) cytotoxicity, cell cycle and induction of apoptosis by annexin
      V was investigated. The sensitivity to DEX, DNR and their combination was tested
      by the MTT assay in human promyelocytic leukemia HL-60, the erythroid blast
      crisis CML K562 cell lines and in 45 children with ALL and AML. Cell cycle
      analysis and annexin-V expression were performed by flow cytometry. It has been
      observed that DEX itself weakly, but significantly caused cytotoxicity in both
      cell lines and in patient samples, especially in initial ALL samples. DEX
      sensitized K562 and HL60, but not patient samples, to cytotoxicity of DNR. The
      percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and
      annexin V staining, was higher after exposure to DEX +/- DNR, when compared to
      respective samples not treated with DEX, in both cell lines but not in patient
      samples. Expression of annexin V induced by DEX in both cell lines was enlarged,
      regardless of the presence of DNR. This difference was not observed in patient
      samples, however, the number of cells expressing annexin V was higher after
      exposure to DEX +/- DNR in comparison to respective samples not treated with DEX.
      In conclusion, it seems that DEX possibly has no impact on the sensitivity of
      childhood leukemic blasts to DNR, however, has weak cytotoxic properties itself.

PMID- 11986943
TI  - A novel mechanism of retinoic acid resistance in acute promyelocytic leukemia
      cells through a defective pathway in telomerase regulation.
AB  - Human telomerase, a cellular reverse transcriptase specifically activated in most
      malignant tumors and usually inactive in normal somatic cells, plays an important
      role in immortalization and tumorigenesis. Early reports have indicated that
      terminal differentiation of various cells is associated with a rapid inhibition
      of telomerase activity, preceded by a down-regulation of telomerase reverse
      transcriptase (hTERT) mRNA. Recently, we have shown that telomerase can be
      repressed by all-trans retinoic acid (ATRA) independently of terminal maturation
      during long-term ATRA treatment of the maturation-resistant promyelocytic
      leukemia cell line (NB4-R1), leading to shortening of telomeres and cell death,
      events overcome by ectopic hTERT expression. Here, we report the isolation of a
      variant of NB4-R1 cells (NB4-R1(SFD)), which bypasses this death step, because of
      a re-activated telomerase, despite the continuous presence of ATRA. While
      unresponsive to a long-term maturation independent regulation of telomerase by
      ATRA, these cells retain a functional pathway of telomerase down-regulation
      associated with retinoid-induced maturation. These findings reinforce the notion
      that two distinct pathways of telomerase regulation by retinoids co-exist in APL
      cells. Noteworthy, we show that the slow developing mechanism, that causes death
      of maturation-resistant cells, is subjected to a new type of retinoid-resistance
      as yet not understood.

PMID- 11986944
TI  - Increased expression of the breast cancer resistance protein (BCRP) in relapsed
      or refractory acute myeloid leukemia (AML).
AB  - Expression of the multidrug resistance proteins P-glycoprotein, encoded by the
      MDR1 gene, multidrug resistance-associated protein (MRP1) and the lung resistance
      related protein or major vault protein (LRP/MVP) is associated with clinical
      resistance to chemotherapy in acute myeloid leukemia (AML). Recently, the breast
      cancer-resistant protein (BCRP), the equivalent of mitoxantrone-resistant protein
      (MXR) or placental ABC transporter (ABCP), was described in AML. We investigated
      MDR1, MRP1, LRP/MVP and BCRP mRNA expression simultaneously in 20 paired clinical
      AML samples from diagnosis and relapse or refractory disease, using quantitative
      Taqman analysis. In addition, standard assays for P-glycoprotein expression and
      function were performed. BCRP was the only resistance protein that was expressed
      at a significantly higher RNA level (median 1.7-fold, P = 0.04) at
      relapsed/refractory state as compared to diagnosis. In contrast, LRP/MVP mRNA
      expression decreased as disease evolved (P = 0.02), whereas MDR1 and MRP1 mRNA
      levels were not different at relapse as compared to diagnosis. Also, at the
      protein level no difference of MDR1 between diagnosis and relapse was found. A
      significant co-expression of BCRP and MDR1 was found at diagnosis (r = 0.47, P =
      0.04). The present results suggest that BCRP, but not MDR1, MRP1 or LRP/MVP is
      associated with clinical resistant disease in AML.

PMID- 11986945
TI  - CD4+CD7- leukemic T cells from patients with Sezary syndrome are protected from
      galectin-1-triggered T cell death.
AB  - In early stages of cutaneous T cell lymphoma (Sezary syndrome) both CD4+CD7- and
      CD4+CD7+ T cells clonally expand whereas in late stages of the disease CD7- cells
      are predominant in number, giving rise to the question whether CD7- T cells have
      a survival advantage in the skin. Galectin-1, a cell-bound lectin, was recently
      reported to trigger apoptosis in activated CD7+ T cells. Here, we demonstrate
      that in contrast to activated CD7(+) T cells, quiescent and activated CD69+ CD7-
      T cells from healthy donors and from Sezary patients are resistant to galectin-1
      mediated cell death. CD7- T cells are apoptosis-resistant even during coculture
      with IFN-gamma-stimulated endothelial cells that constitutively express galectin
      1 in high amounts. These data imply that resistance of CD7- T cells to galectin-1
      induced apoptosis may contribute to the accumulation of CD7- Sezary T cells
      during progression of the disease.

PMID- 11986946
TI  - The coexpression of the apoptosis-related genes bcl-2 and wt1 in predicting
      survival in adult acute myeloid leukemia.
AB  - The Wilms tumor gene wt1 and the protooncogene bcl-2 are upregulated in acute
      myeloid leukemia (AML) and are known to regulate or to inhibit the onset of
      apoptosis. Since wt1 has been shown to regulate the expression of bcl-2, we
      investigated the association of the expression of these genes and their
      prognostic relevance in AML. Leukemic blasts from the bone marrow of 152 patients
      with newly diagnosed AML were analyzed for bcl-2 and wt1 mRNA expression using RT
      PCR and quantitative PCR. Therapy outcome was correlated with the level of bcl-2
      and wt1 transcripts. Bcl-2-specific mRNA was detectable in 127/152 (84%) patients
      and wt1 mRNA in 113/152 (74%) patients with AML. In monocytic subtypes the
      frequency of bcl-2 and wt1 transcripts was significantly lower. The expression of
      bcl-2 mRNA was correlated significantly with that of wt1 mRNA (P < 0.0001). In
      AML patients <60 years, high expression of bcl-2 and wt1 was associated with a
      reduced rate of continuing complete remission (CCR, P = 0.002 and P = 0.005,
      respectively) and increased death rate (P = 0.0002 and P = 0.04, respectively) in
      contrast to patients >60 years, where the expression of bcl-2 or wt1 had no
      prognostic impact. Based on the coexpression of bcl-2 and wt1, we established a
      prognostic model defining three risk groups with significant differences in CCR
      rate (P = 0.01), overall survival (P < 0.04) and disease-free survival (P <
      0.03). Thus, bcl-2 and wt1 mRNA expression are associated with response and long
      term outcome in AMLs. The coexpression of these genes allows determination of
      prognostic groups with high predictive value for overall and disease-free
      survival.

PMID- 11986947
TI  - A novel mechanism of antitumor response involving the expansion of CD3+/CD56+
      large granular lymphocytes triggered by a tumor-expressed activating ligand.
AB  - We describe a patient with acute myeloid leukemia (AML) who developed polyclonal
      large granular lymphocyte (LGL) proliferation. The reciprocal evolution of AML
      and LGLs suggested that these LGLs had an anti-tumor activity. The patient's LGLs
      killed autologous leukemia cells in a different way to classical T lymphocyte
      mediated cytotoxicity since it did not rely on the recognition of target antigens
      presented by major histocompatibility complex (MHC) class I molecules by the
      CD3/TcRalphabeta complex. This killing was also different from natural killer
      (NK)-mediated cytotoxicity, which depends on the absence of MHC class I molecule
      recognition by NK inhibitory receptors. The LGLs were polyclonal, had a
      CD3+/CD8+/CD56+ phenotype, and did not express the natural killer cell receptors
      (NKRs) for MHC class I molecules. The LGLs did not express the NK-specific
      activating natural cytotoxicity receptors but expressed the 2B4 non-MHC
      restricted triggering receptor, whose ligand CD48 was expressed by leukemic cells
      and normal bone marrow cells. The 2B4 receptor participated in the ability of
      LGLs to lyse patient's leukemia. This represents a novel function for 2B4 in man,
      since this molecule, at variance with the murine system, was considered not to
      have direct effects on CD8+ T cell-mediated cytotoxicity. This case report
      allowed us to describe a novel T lymphocyte-mediated anti-tumor mechanism which
      relied on (1) the abnormal expansion of the rare 2B4-positive CD3+/CD8+/CD56+ T
      lymphocyte subset, (2) an as yet undescribed cytotoxicity mechanism in man which
      depended on 2B4 molecule. The relevance of this observation in human cancer
      immunotherapy has to be further investigated.

PMID- 11986948
TI  - Phenotypic transformation of CD52(pos) to CD52(neg) leukemic T cells as a
      mechanism for resistance to CAMPATH-1H.
AB  - Immunotherapy utilizing CAMPATH-1H for patients with chemotherapy-refractory
      chronic lymphocytic leukemia has yielded encouraging results with many reports of
      complete remission. Here we report the outcome of two patients with CD4-positive
      T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded
      rapidly to treatment and subsequently developed CD4 lymphopenia. One patient
      remained in complete remission after 14 weeks of treatment. Serial peripheral
      blood flow cytometry revealed that the CD52 antigen was present throughout
      treatment. The other patient who was initially CD52-positive, became CD52
      negative after 6 weeks of treatment, and developed progressive symptoms of T cell
      prolymphocytic leukemia. Immunotherapy was stopped, chemotherapy proved futile,
      and the patient died. This change in phenotype from CD52-positive to -negative
      during CAMPATH-1H therapy points out a need to develop strategies for maintaining
      antigenic expression during monoclonal antibody therapy.

PMID- 11986949
TI  - Human plasma contains a soluble form of CD86 which is present at elevated levels
      in some leukaemia patients.
AB  - Cell surface expression of CD86 (mCD86) provides an important co-stimulatory
      signal which profoundly influences immune responses. In this report, we
      investigated the potential presence of a circulating soluble form of CD86 (sCD86)
      in normal individuals and patients with acute myeloid leukaemia (AML) or B cell
      chronic lymphocytic leukaemia (B-CLL). Circulating sCD86 was detected in the
      plasma of all normal individuals (1.04 +/- 0.33 ng/ml, n = 51) and patients
      analysed. Plasma collected from AML patients in remission (n = 6) contained only
      low levels of sCD86 but significantly elevated levels (> or =2.65 ng/ml, P <
      0.0001) were detected in 10/24 AML patients analysed at the time of presentation
      or relapse. Significantly elevated levels of sCD86 were also detected in 2/17 B
      CLL patients. There was no correlation between sCD86 levels and other clinical
      parameters. RT-PCR analysis demonstrated that normal monocytes and dendritic
      cells, as well as isolated AML (n = 2) and B-CLL (n = 4) cells, expressed an
      alternatively spliced transcript of CD86 which encoded a soluble form absent in
      normal T, B and NK cells. The finding that a proportion of leukaemia patients
      contain elevated levels of sCD86 and that at least some leukaemic cells express
      sCD86 transcript suggests a potential role for sCD86 in modulating mCD86
      signalling during the malignant process.

PMID- 11986950
TI  - Potential involvement of the AML1-MTG8 fusion protein in the granulocytic
      maturation characteristic of the t(8;21) acute myelogenous leukemia revealed by
      microarray analysis.
AB  - The AML1 (RUNX1)-MTG8 (ETO) fusion transcription factor generated by the t(8;21)
      translocation is believed to deregulate the expression of genes that are crucial
      for normal differentiation and proliferation of hematopoietic progenitors,
      resulting in acute myelogenous leukemia. To elucidate the role of AML1-MTG8 in
      leukemogenesis, we used oligonucleotide microarrays to detect alterations in gene
      expression caused by ectopic expression of AML1-MTG8 in a murine myeloid
      progenitor cell line, L-G. Microarray analysis of approximately 6500 genes
      identified 32 candidate genes under the downstream control of AML1-MTG8. Among
      the 32 genes, 23 were not known to be regulated by AML1-MTG8. These included many
      granule protein genes and several cell surface antigen genes. Interestingly, AML1
      MTG8 enhanced the expression of several genes that are usually induced during
      granulocytic differentiation, particularly those encoding azurophil granule
      proteins, including cathepsin G, myeloperoxidase and lysozyme. This indicates
      that AML1-MTG8 induces partial differentiation of myeloid progenitor cells into
      promyelocytes in the absence of the usual differentiation signals, while it
      inhibits terminal differentiation into mature granulocytes. Thus, AML1-MTG8
      itself may play a crucial role in defining a unique cytologic type with abnormal
      maturation, characteristic of t(8;21) acute myelogenous leukemia.

PMID- 11986951
TI  - Preferential expression of the transcription coactivator HTIF1alpha gene in acute
      myeloid leukemia and MDS-related AML.
AB  - HTIF1alpha, a transcription coactivator which is able to mediate RARalpha
      activity and functionally interact with PML, is encoded by a gene on chromosome
      7q32-34, which is a critical region in acute myeloid leukemias (AML). With the
      assumption that this gene may be related to AML, we investigated the HTIF1alpha
      DNA structure and RNA expression in leukemic cells from 36 M1-M5 AML patients (28
      "de novo" and eight "secondary" to myelodysplastic syndrome (MDS)). Abnormal
      HTIF1alpha DNA fragments were never found, whereas loss of HTIF1alpha DNA was
      observed in the patients with chromosome 7q32 deletion and translocation, and in
      one case without detectable chromosome 7 abnormality. HTIF1alpha RNA was found in
      acute myelocytic leukemic blasts, and was almost undetectable in normal
      mononuclear cells. The expression varied among the patients: higher in M1 to M3
      subtypes, with the highest values in M1; low levels were constantly observed in
      M4 and M5 AML. In addition, HTIF1alpha was significantly overexpressed in MDS
      related AML (MDR-AML), but not in MDS. We also found that HTIF1alpha expression
      was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells,
      induced to differentiate along the monocytic-macrophage pathway by TPA or vitamin
      D3, HTIF1alpha expression decreased, whereas it was maintained at high levels on
      induction to granulocytic differentiation by RA or DMSO. In K562 cells,
      HTIF1alpha RNA levels did not change after hemin-induced erythroid
      differentiation. These results suggest that HTIF1alpha could play a role in
      myeloid differentiation, being distinctly regulated in hematopoietic lineages.

PMID- 11986952
TI  - Expression of a mutated form of the p85alpha regulatory subunit of
      phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO).
AB  - Phosphatidylinositol (PI) 3-kinase plays an important role in a variety of
      biological processes, including proliferation and apoptosis. PI3-kinase is a
      heterodimer consisting of an 85 kDa adapter protein (p85) containing one SH3
      domain and two SH2 domains and a 110 kDa catalytic subunit (p110). Recently an
      oncogenic form of p85 named p65-PI3K lacking the C-terminal SH2 domain has been
      cloned from an irradiation-induced murine thymic lymphoma and transgenic mice
      expressing p65-PI3K in T lymphocytes develop a lymphoproliferative disorder. Here
      we describe the cloning of a C-terminal truncated form of p85 expressed in a
      human lymphoma cell line (CO) with a T cell phenotype derived from a patient with
      Hodgkin's disease. As a result of a frame-shift mutation at amino acid 636, p76
      is lacking most of the C-terminal SH2 domain, but contains the inter-SH2 domain
      and is associated with an active form of PI3-kinase. A PI3-kinase-dependent
      constitutive activation of Akt was detected in CO cells which was only partially
      reduced after serum starvation. Treatment of CO cells with the PI3-kinase
      inhibitor wortmannin resulted in a concentration-dependent inhibition of cell
      proliferation associated with an increased number of apoptotic cells. This is the
      first detection of a mutated form of the p85 subunit of PI3-kinase in human
      hematopoietic cells further underlining a potential role of PI3-kinase/Akt
      signaling in human leukemogenesis.

PMID- 11986953
TI  - N-(4-hydroxyphenyl)retinamide increases ceramide and is cytotoxic to acute
      lymphoblastic leukemia cell lines, but not to non-malignant lymphocytes.
AB  - The retinoid, N-(4-hydroxyphenyl)retinamide (4-HPR), mediates p53-independent
      cytotoxicity and can increase reactive oxygen species and ceramide in solid tumor
      cell lines. We determined changes in ceramide and cytotoxicity upon treatment
      with 4-HPR (3-12 microM) in six human acute lymphoblastic leukemia (ALL) cell
      lines: T cell (MOLT-3, MOLT-4, CEM), pre-B-cell (NALM-6, SMS-SB), and null cell
      (NALL-1). Exposure to 4-HPR (12 microM) for 96 h caused 4.7 (MOLT-3), 3.5 (MOLT
      4), 3.9 (CEM), 2.9 (NALM-6), 4.7 (SMS-SB), AND 4.5 (NALL-1) logs of cell kill.
      The average 4-HPR concentration that killed 99% of cells (LC(99)) for all six
      lines was 4.8 microM (range: 1.5-8.9 microM). Treatment with 4-HPR (9 microM) for
      24 h resulted in an 8.9 +/- 1.0-fold (range: 4.9-15.7-fold) increase of ceramide.
      Ceramide increase was time- and dose-dependent and abrogated by inhibitors of de
      novo ceramide synthesis. Concurrent inhibition of ceramide
      glycosylation/acylation by d,l-threo-(1-phenyl-2-hexadecanoylamino-3-morpholino-1
      propanol) (PPMP) further increased ceramide levels, and synergistically increased
      4-HPR cytotoxicity in four of six ALL cell lines. 4-HPR was minimally cytotoxic
      to peripheral blood mononuclear cells and a lymphoblastoid cell line, and
      increased ceramide <2-fold. Thus, 4-HPR was cytotoxic and increased ceramide in
      ALL cell lines, but not in non-malignant lymphoid cell types.

PMID- 11986954
TI  - B-CLL cells are capable of synthesis and secretion of both pro- and anti
      angiogenic molecules.
AB  - Initial work has shown that clonal B cells from B-chronic lymphocytic leukemia (B
      CLL) are able to synthesize pro-angiogenic molecules. In this study, our goal was
      to study the spectrum of angiogenic factors and receptors expressed in the CLL B
      cell. We used ELISA assays to determine the levels of basic fibroblast growth
      factors (bFGF), vascular endothelial growth factor (VEGF), endostatin, interferon
      alpha (IFN-alpha) and thrombospondin-1 (TSP-1) secreted into culture medium by
      purified CLL B cells. These data demonstrated that CLL B cells spontaneously
      secrete a variety of pro- and anti-angiogenic factors, including bFGF (23.9 pg/ml
      +/- 7.9; mean +/- s.e.m.), VEGF (12.5 pg/ml +/- 2.3) and TSP-1 (1.9 ng/ml +/-
      0.3). Out of these three factors, CLL B cells consistently secreted bFGF and TSP
      1, while VEGF was expressed in approximately two-thirds of CLL patients. Of
      interest, hypoxic conditions dramatically upregulated VEGF expression at both the
      mRNA and protein levels. We also employed ribonuclease protection assays to assay
      CLL B cell expression of a variety of other angiogenesis-related molecules. These
      analyses revealed that CLL B cells consistently express mRNA for VEGF receptor 1
      (VEGFR1), thrombin receptor, endoglin, and angiopoietin. Further analysis of
      VEGFR expression by RT-PCR revealed that CLL B cells expressed both VEGFR1 mRNA
      and VEGFR2 mRNA. In summary, these data collectively indicate that CLL B cells
      express both pro- and anti-angiogenic molecules and several vascular factor
      receptors. Because of the co-expression of angiogenic molecules and receptors for
      some of these molecules, these data suggest that the biology of the leukemic
      cells may also be directly impacted by angiogenic factors as a result of
      autocrine pathways of stimulation.

PMID- 11986955
TI  - Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in
      children with acute myeloid leukemia.
AB  - The purpose of this study was to assess the effect of the multidrug resistance
      modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and
      mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood
      samples for pharmacokinetic studies were obtained in 38 children over a 24-h
      period following cytotoxin treatment with or without CsA on days 1 and 4. Drug
      concentrations were quantitated using validated HPLC methods, and pharmacokinetic
      parameters were determined using compartmental modeling with an iterative two
      stage approach, implemented on ADAPT II software. Etoposide displayed a greater
      degree of interindividual variability in clearance and systemic exposure than
      mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance
      declined by 71% and 42%, respectively. These effects on clearance, in combination
      with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and
      12% increases in the mean AUC for etoposide and mitoxantrone, respectively. There
      were no differences in the rates of stomatitis or infection between the two
      groups. CsA treatment resulted in an increased incidence of hyperbilrubinemia,
      which rapidly reversed upon conclusion of drug therapy. The variability observed
      in clearance, combined with the empiric 40% dose reduction of the cytotoxins,
      resulted in statistically similar systemic exposure and similar toxicity.

PMID- 11986956
TI  - Immunoglobulin kappa deleting element rearrangements in precursor-B acute
      lymphoblastic leukemia are stable targets for detection of minimal residual
      disease by real-time quantitative PCR.
AB  - Immunoglobulin gene rearrangements are used as PCR targets for detection of
      minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We
      investigated the occurrence of monoclonal immunoglobulin kappa-deleting element
      (IGK-Kde) rearrangements by Southern blotting and PCR/heteroduplex analysis at
      diagnosis, their stability at relapse, and their applicability in real-time
      quantitative PCR (RQ-PCR) analysis. In 77 selected children with precursor-B-ALL,
      Southern blotting detected 122 IGK-Kde rearrangements, 12 of which were derived
      from subclones in six patients (8%). PCR/heteroduplex analysis with BIOMED-1
      Concerted Action primers identified 100 of the 110 major IGK-Kde rearrangements
      (91%). Comparison between diagnosis and relapse samples from 21 patients with PCR
      detectable IGK-Kde rearrangements (using Southern blotting, PCR/heteroduplex
      analysis, and sequencing) demonstrated that 27 of the 32 rearrangements remained
      stable at relapse. When patients with oligoclonal IGK-Kde rearrangements were
      excluded, 25 of the 27 rearrangements remained stable at relapse and at least one
      stable rearrangement was present in 17 of the 18 patients. Subsequently, RQ-PCR
      analysis with allele-specific forward primers, a germline Kde TaqMan-probe, and a
      germline Kde reverse primer was evaluated for 18 IGK-Kde rearrangements. In 16 of
      the 18 targets (89%) a sensitivity of < or =10(-4) was reached. Analysis of MRD
      during follow-up of eight patients with IGK-Kde rearrangements showed comparable
      results between RQ-PCR data and classical dot-blot data. We conclude that the
      frequently occurring IGK-Kde rearrangements are generally detectable by PCR (90%)
      and are highly stable MRD-PCR targets, particularly where monoclonal
      rearrangements at diagnosis (95%) are concerned. Furthermore, most IGK-Kde
      rearrangements (90%) can be used for sensitive detection of MRD (< or =10(-4)) by
      RQ-PCR analysis.

PMID- 11986957
TI  - Lack of somatic hypermutation of IG V(H) genes in lymphoid malignancies with
      t(2;14)(p13;q32) translocation involving the BCL11A gene.
AB  - The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is a rare but recurrent
      chromosomal aberration in B-cell malignancies. Hitherto, juxtaposition of BCL11A
      and IGH has only been described in B-cell chronic lymphocytic leukemia (B-CLL)
      and immunocytoma. As subgroups of B-CLL can be distinguished by the pattern of
      somatic mutation of immunoglobulin variable (V) genes we investigated four
      lymphomas with IGH/BCL11A involvement for IGH hypermutation. Clonal V(H) gene
      rearrangements were amplified; in all four cases, sequencing of the amplificates
      revealed the rearranged V(H) genes to lack somatic mutations. These results
      suggest that t(2;14)(p13;q32.3) is associated with a subset of B-CLL/immunocytoma
      characterized by non-mutated IG genes deriving from pre-germinal center B cells.
      As the translocations in both informative cases are targeted to the switch
      regions of the IGG2 gene, which is mainly used in T cell-independent immune
      responses, these translocations presumably occurred in activated B cells in the
      course of T cell-independent immune responses outside the germinal center.

PMID- 11986958
TI  - All-trans retinoic acid down-regulates prion protein expression independently of
      granulocyte maturation.
AB  - The cellular prion protein (PrPc) is a sialoglycoprotein involved in the
      pathogenesis of prion diseases. It has been identified at the plasma membrane of
      several cell types. All-trans retinoic acid (ATRA) is known to induce
      differentiation of human leukemia cell lines in vitro. PrPc messenger ribonucleic
      acid (mRNA) and protein are down-regulated upon ATRA-induced differentiation of
      HL60 cells. In this report, we have investigated the regulation of PrPc mRNA and
      protein expression during ATRA-treatment of maturation-sensitive (NB4) and 
      resistant (NB4-R1 and NB4-R2) cell lines. In ATRA-induced maturation of NB4
      cells, down-regulation of PrPc mRNA and protein were observed. We also show that
      down-regulation of PrPc mRNA is dependent on protein synthesis. Moreover, the
      same down-regulation of prion protein by ATRA was observed at the surface of
      maturation-resistant, ATRA-responsive NB4-R1 cells. In contrast, the maturation
      resistant and ATRA-unresponsive NB4-R2 subline showed no variation in membrane
      prion protein expression. These results demonstrate a dissociation between the
      regulation of prion protein expression by ATRA and the process of granulocyte
      maturation. We propose that retinoids should be investigated further as a
      preventive strategy to slow down prion disease progression.

PMID- 11986960
TI  - ABL gene fuses BCR during t(20;22) results in Philadelphia-negative, but BCR/ABL
      positive chronic myeloid leukemia.

PMID- 11986959
TI  - Infants with acute lymphoblastic leukemia: no evidence for high methotrexate
      resistance.

PMID- 11986961
TI  - Chromosome 11q deletion in myeloid malignancies.

PMID- 11986962
TI  - Distinct genomic events in the myeloid and lymphoid lineages in simultaneous
      presentation of chronic myeloid leukemia and B-chronic lymphocytic leukemia.

PMID- 11986963
TI  - Germline mutation of the p27/Kip1 gene in childhood acute lymphoblastic leukemia.

PMID- 11986964
TI  - Human herpesvirus-6 as a possible cause of encephalitis and hemorrhagic cystitis
      after allogeneic hematopoietic stem cell transplantation.

PMID- 11986965
TI  - Comment on 'Functional disturbance of marrow stromal microenvironment in the
      myelodysplastic syndromes' by S Tauro et al.

PMID- 11986967
TI  - Orbital granulocytic sarcoma and AML with poor prognosis in Turkish children.

PMID- 11986969
TI  - Screening for core binding factor gene rearrangements in acute myeloid leukemia.

PMID- 11986972
TI  - Autoimmunity in autism.

PMID- 11986975
TI  - Sex differentiated hypothalamic activation by putative pheromones.

PMID- 11986976
TI  - Map of candidate genes and STSs on 18p11.2, a bipolar disorder and schizophrenia
      susceptibility region.

PMID- 11986977
TI  - The missense mutation in the WKL1 gene not found in patients with bipolar
      affective disorder.

PMID- 11986978
TI  - Manic-depression genes and the new millennium: poised for discovery.
AB  - Manic-depressive illness is a common psychiatric disorder with complex etiology
      that likely involves multiple genes and non-genetic influences. The uncertain
      path to gene discovery has spurred considerable debate over genetic findings and
      gene-finding strategies. In this article, I review the main findings, with a
      focus on: (1) putative linked loci on chromosomes 1q31-32, 4p16, 6pter-p24,
      10p14, 10q21-26, 12q23-24, 13q31-32, 18p11, 18q21-23, 21q22, 22q11-13, and Xq24
      28; and (2) association studies with candidate genes, dynamic mutations,
      mitochondrial mutations, and chromosomal aberrations. Although no gene has been
      identified, promising findings are emerging. I then discuss the challenges and
      opportunities ahead, with special emphasis on gene-finding methods-in particular,
      questions pertaining to phenotype definition, linkage and association mapping,
      gene markers, sampling, study population, multigene systems, lessons from other
      disorders, animal models, and bioinformatics. The progress to date, together with
      rapid advances in genomics, analytical and computational methods, and
      bioinformatics, holds promise for new insights into the genetics of manic
      depression, in the new millennium.

PMID- 11986979
TI  - Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal
      neurons by L-phenylalanine at concentrations observed during phenylketonuria.
AB  - Hippocampal N-methyl-D-aspartate receptors (NMDARs) are thought to be involved in
      the regulation of memory formation and learning. Investigation of NMDAR function
      during experimental conditions known to be associated with impaired cognition in
      vivo may provide new insights into the role of NMDARs in learning and memory.
      Specifically, the mechanism whereby high concentrations of L-phenylalanine (L
      Phe) during phenylketonuria (>1.2 mM) cause mental retardation remains unknown.
      Therefore, the effects of L-Phe on NMDA-activated currents (I(NMDA)) were studied
      in cultured hippocampal neurons from newborn rats using the patch-clamp
      technique. L-Phe specifically and reversibly attenuated I(NMDA) in a
      concentration-dependent manner (IC(50) = 1.71 +/- 0.24 mM). In contrast, L
      tyrosine (L-Tyr), an amino acid synthesized from L-Phe in normal subjects, did
      not significantly change I(NMDA). Although the L-Phe-I(NMDA) concentration
      response relationship was independent of the concentration of NMDA, it was
      shifted rightward by increasing the concentration of glycine. Consistent with an
      effect of L-Phe on the NMDAR glycine-binding site, L-Phe (1 mM) did not attenuate
      I(NMDA) in the presence of D-alanine (10 microM). Furthermore, L-Phe
      significantly attenuated neither glutamate-activated current in the presence of
      MK-801, nor current activated by AMPA. The finding that L-Phe inhibits
      specifically NMDAR current in hippocampal neurons by competing for the glycine
      binding site suggests a role for impaired NMDAR function in the development of
      mental retardation during phenylketonuria and accordingly an important role for
      NMDARs in memory formation and learning.

PMID- 11986980
TI  - Child psychopathology and lower cognitive ability: a general population twin
      study of the causes of association.
AB  - Previous work has demonstrated associations between lower cognitive ability and
      childhood and adult non-psychotic psychopathology. As both cognitive ability (CA)
      and child psychopathology (CP) are influenced by genetic factors, one explanation
      for the association is that they are the pleiotropic manifestations of the same
      underlying genetic factors. The present paper examines three possible causes of
      the association: additive genetic factors, common environmental factors and
      individual-specific environmental factors. Three hundred and seventy-six twin
      pairs from the East Flanders Prospective Twin Survey were examined with the Child
      Behaviour Checklist and the Wechsler Intelligence Scale for Children-Revised. The
      cross-twin within-variable, within-twin cross-variable and cross-twin cross
      variable correlations were calculated. Using structural equation modelling,
      bivariate models were fitted. The best fitting model was chosen, based on
      likelihood and parsimony. The observed phenotypic correlation between CP and CA
      was -0.19 (95% CI: -0.09, -0.27), with genetic factors accounting for about 84%
      of the observed correlation. Bivariate model fitting quantified the genetic
      correlation between CP and CA at -0.27 (95% CI: -0.12, -0.42) and the individual
      specific environmental correlation at -0.17 (95% CI: -0.03, -0.31). In children,
      three different genetic factors may exist: one that solely affects the liability
      to CP, one that has only an effect on CA and one that influences both CP and CA.
      While individual-specific environmental factors can influence the liability to
      both traits, our results suggest that most of the environmental factors that
      increase the risk of CP do not influence CA and vice versa.

PMID- 11986981
TI  - Small intestinal enteropathy with epithelial IgG and complement deposition in
      children with regressive autism.
AB  - We have reported lymphocytic colitis in children with regressive autism, with
      epithelial damage prominent. We now compare duodenal biopsies in 25 children with
      regressive autism to 11 with coeliac disease, five with cerebral palsy and mental
      retardation and 18 histologically normal controls. Immunohistochemistry was
      performed for lymphocyte and epithelial lineage and functional markers. We
      determined the density of intraepithelial and lamina propria lymphocyte
      populations, and studied mucosal immunoglobulin and complement C1q localisation.
      Standard histopathology showed increased enterocyte and Paneth cell numbers in
      the autistic children. Immunohistochemistry demonstrated increased lymphocyte
      infiltration in both epithelium and lamina propria with upregulated crypt cell
      proliferation, compared to normal and cerebral palsy controls. Intraepithelial
      lymphocytes and lamina propria plasma cells were lower than in coeliac disease,
      but lamina propria T cell populations were higher and crypt proliferation
      similar. Most strikingly, IgG deposition was seen on the basolateral epithelial
      surface in 23/25 autistic children, co-localising with complement C1q. This was
      not seen in the other conditions. These findings demonstrate a novel form of
      enteropathy in autistic children, in which increases in mucosal lymphocyte
      density and crypt cell proliferation occur with epithelial IgG deposition. The
      features are suggestive of an autoimmune lesion.

PMID- 11986982
TI  - The dopamine D4 receptor and the hyperactivity phenotype: a developmental
      epidemiological study.
AB  - Attention-deficit hyperactivity disorder (ADHD) affects 2-6% of school-age
      children and is a precursor of behavioural problems in adolescence and adulthood.
      Underlying the categorical definition of ADHD are the quantitative traits of
      activity, impulsivity, and inattention which vary continuously in the population.
      Both ADHD and quantitative measures of hyperactivity are heritable, and
      influenced by multiple genes of small effect. Several studies have reported an
      association between clinically defined ADHD and the seven-repeat allele of a 48
      bp tandem repeat polymorphism in the third exon of the dopamine D4 receptor gene
      (DRD4). We tested this association in a large, unselected birth cohort (n = 1037)
      using multiple measures of the hyperactivity phenotype taken at multiple
      assessment ages across 20 years. This longitudinal approach allowed us to
      ascertain whether or not DRD4 has a general effect on the diagnosed (n = 49) or
      continuously distributed hyperactivity phenotype, and related personality traits.
      We found no evidence to support this association.

PMID- 11986983
TI  - Molecular abnormalities in the major psychiatric illnesses: Classification and
      Regression Tree (CRT) analysis of post-mortem prefrontal markers.
AB  - Post-mortem specimens from the Stanley Foundation Neuropathology Consortium,
      which contains matched samples from patients with schizophrenia, bipolar
      disorder, non-psychotic depression and normal controls (n = 15 per group), have
      been distributed to many research groups around the world. This paper provides a
      summary of abnormal markers found in prefrontal cortical areas from this
      collection between 1997 and 2001. With parametric analyses of variance of 102
      separate data sets, 14 markers were abnormal in at least one disease. The markers
      pertained to a variety of neural systems and processes including neuronal
      plasticity, neurotransmission, signal transduction, inhibitory interneuron
      function and glial cells. The data sets were also examined using the non
      parametric Classification and Regression Tree (CRT) technique for the four
      diagnostic groups and in pair-wise combinations. In contrast to the results
      obtained with analyses of variance, the CRT method identified a smaller set of
      nine markers that contributed maximally to the diagnostic classifications. Three
      of the nine markers observed with CRT overlapped with the ANOVA results. Six of
      the nine markers observed with the CRT technique pertained to aspects of
      glutamatergic, GABA-ergic, and dopaminergic neurotransmission.

PMID- 11986984
TI  - Meta-analysis of whole-genome linkage scans of bipolar disorder and
      schizophrenia.
AB  - Badner and Gershon (2001) presented a technique of meta-analysis of linkage data
      that could be applied to published genome scans. It combines the reported P
      values of individual studies, after correcting each value for the size of the
      region containing a minimum P-value. Simulations demonstrated that the type I
      error rate was at least as low as that for a single genome scan and thus genome
      wide significance criteria may be applied. Power to detect linkage was at least
      as high as the power of pooling the data from all the studies. We applied this
      method to all the published genome scans for bipolar disorder and schizophrenia.
      We found the strongest evidence for susceptibility loci on 13q (P < 6 x 10(-6))
      and 22q (P < 1 x 10(-5)) for bipolar disorder, and on 8p (P < 2 x 10(-4)), 13q (P
      < 7 x 10(-5)), and 22q (P < 9 x 10(-5)) for schizophrenia.

PMID- 11986985
TI  - An association between a missense polymorphism in the close homologue of L1
      (CHL1, CALL) gene and schizophrenia.
AB  - Morphological alterations in the brains of schizophrenia patients suggest that
      neurodevelopmental dysfunction is involved in the etiology of the disease.(1)
      Such dysfunction may be due to functional alterations of cell adhesion molecules,
      which play important roles in cell migration, axonal growth, fasciculation,
      synaptogenesis, and synaptic remodeling. We screened for mutations in the coding
      region of the close homologue to L1 gene (CHL1), which is located on human
      chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense
      polymorphism (Leu17Phe) in the signal peptide region was identified. A case
      control comparison revealed significantly higher frequencies of the Leu/Leu
      genotype (P = 0.004) and the Leu allele (P = 0.006) in 282 Japanese schizophrenic
      patients than in 229 Japanese control subjects. The estimated odds ratio for
      schizophrenia was 1.83 (95% CI, 1.28-2.26) for the Leu/Leu genotype compared with
      the other genotypes. An association between this CHL1 gene polymorphism and
      schizophrenia supports the notion that cell adhesion molecules are involved in
      the etiology of schizophrenia.

PMID- 11986986
TI  - Association between the ionotropic glutamate receptor kainate 3 (GRIK3) ser310ala
      polymorphism and schizophrenia.
AB  - Schizophrenia is a severe psychiatric illness characterised by disturbance of
      thought, hallucination and delusions.(1) Several studies have suggested that
      dysfunctions in the glutamatergic transmission are linked to the pathogenesis of
      schizophrenia, and in particular an excessive activation of glutamate receptors
      seems to be related to the disruption of neuronal ionic gradients leading to
      excitotoxicity.(2-7) Numerous findings suggested that the kainate ionotropic
      glutamate receptors are primarily involved in this mechanism. Recently it has
      been demonstrated that the GRIK3 gene encoding for the ionotropic glutamate
      receptor kainate 3 contains a functional polymorphism (T928G) leading to the
      substitution of a serine with an alanine in position 310 of the protein
      sequence.(8-11) We performed an association study between the ser310ala
      GRIK3polymorphism and schizophrenia in a sample of 99 schizophrenic patients and
      116 controls. We found a significant difference in the genotype distribution and
      in particular considering the ala allele as dominant (P = 0.0105, odds ratio (OR)
      2.031, 95% confidence interval (CI) 1.177-3.504). This finding suggests a
      potential role for GRIK3 for susceptibility to schizophrenia.

PMID- 11986987
TI  - No missense mutation of WKL1 in a subgroup of probands with schizophrenia.
AB  - Recently, a Leu309Met mutation in WKL1 (MLC1, KIAA0027), a gene mapped to
      chromosome 22q13.33, was reported to co-segregate with periodic catatonia, a
      clinical sub-type of schizophrenia, in seven members of an extended pedigree.(1)
      WKL1 encodes a putative membrane protein expressed exclusively in the brain,
      particularly in the amygdala, nucleus caudatus, thalamus, and hippocampus.(1) We
      screened WKL1 for etiologic mutations in 28 probands from the United States who
      were given a consensus diagnosis of schizophrenia and met at least one of these
      criteria: (1) were from multiplex schizophrenia families where at least two
      schizophrenic subjects were reported to display catatonic behavior at sometime
      during the course of their illness; or (2) were from multiplex schizophrenia
      families where, in a genome scan for schizophrenia susceptibility loci, evidence
      for excess allele sharing among affected family members for markers in the 22q13
      region was seen. In addition, 15 affected subjects from 15 German pedigrees were
      similarly screened for causative mutations. This German cohort exhibited the
      catatonia phenotype but had ambiguous linkage to 22q13 and included the mutation
      positive proband as a positive control. The 43 probands were screened for base
      changes in WKL1: 15 SNPs in the non-coding regions of the gene, three SNPs in the
      3'UTR, four synonymous coding SNPs and two non-synonymous (amino acid changing)
      SNPs were identified. We were able to rapidly confirm the Leu309Met nucleotide
      change in the positive control. No missense mutations were detected in any of the
      other 42 probands studied. These data exclude the role of WKL1 in schizophrenia
      susceptibility in the subjects studied.

PMID- 11986988
TI  - Evidence for familial cosegregation of major affective disorder and genetic
      markers flanking the gene for Darier's disease.
AB  - Darier's disease is a rare autosomal dominantly inherited keratosis.(1) We have
      previously reported a family in which major affective disorder co-segregated with
      Darier's disease, consistent with linkage between the Darier gene and a
      susceptibility locus for affective illness (max lod = 2.1).(2) The Darier gene
      has been mapped to 12q 23-q24.1 and identified as ATP2A2, a gene encoding SERCA2
      a sarcoplasmic/endoplasmic reticulum calcium pump that plays a role in
      intracellular calcium signalling.(3) A number of groups have reported independent
      evidence of linkage between bipolar disorder and markers in this region.(4) We
      here describe a further Caucasian family of European origin in which there is co
      occurrence of Darier's disease and major affective disorder including bipolar
      disorder and report the results of linkage analysis employing genetic markers
      flanking the Darier's gene. The pedigree includes two individuals with mood
      disorder from a branch of the family not affected with Darier's disease. However,
      there is a new mutation in the Darier (ATP2A2) gene in this family and all
      individuals affected by mood disorder show co-segregation with a haplotype in the
      region of the Darier's gene (max lod = 3.58). The family provides strong evidence
      against the Darier-causing mutation itself playing a major role in affective
      disorder but strongly supports the existence of a bipolar disorder susceptibility
      gene in the Darier region.

PMID- 11986989
TI  - Molecular and cellular mechanisms underlying mood stabilization in bipolar
      disorder: implications for the development of improved therapeutics.

PMID- 11986990
TI  - What makes a drug a primary mood stabilizer?
AB  - The term 'mood stabilizer' has been applied to a number of medications for the
      treatment of patients with bipolar disorder. The operational definition of the
      properties of a mood-stabilizing medication has varied according to the
      properties of specific medications and the clinical characteristics of the
      illness. Randomized controlled trials of agents accepted or proposed as mood
      stabilizers are reviewed to marshall the available evidence in support of this
      claim. In addition, potential pharmacological mechanisms underlying mood
      stabilizing effects of established compounds are reviewed.

PMID- 11986991
TI  - Antidepressant mechanisms: functional and molecular correlates of excitatory
      amino acid neurotransmission.
AB  - Specific targeting of the serotonergic and noradrenergic systems for the
      development of antidepressant compounds has resulted in drugs with more
      favourable side-effect profiles but essentially no greater efficacy than those
      compounds discovered more than 40 years ago. Alternative targets are now being
      considered in the hope that they will have a faster onset of action and be useful
      for those patients currently unresponsive to conventional treatments. Excitatory
      amino acid neurotransmission has been attributed various roles in both normal and
      abnormal brain function. The N-methyl-D-aspartate receptor in particular has long
      been postulated to play a role in the formation of memories. Major depressive
      disorder is characterised by alterations in cognitive function, as well as
      affect. Although there is evidence that early adverse events and stress can have
      a causal influence on depression, the underlying neurobiology of the disorder is
      poorly understood. This review will document current evidence for the involvement
      of excitatory amino acid neurotransmission in the pathophysiology of the
      affective disorders. The preclinical literature suggests that both
      electroconvulsive stimulation and antidepressant drugs can affect hippocampal
      long-term potentiation and the expression of excitatory amino acid receptor
      subtypes. Exposing animals to stress, including the kind that produces learned
      helplessness, can also affect synaptic plasticity in the hippocampus. There is
      clinical evidence that patients with chronic depression have structural brain
      abnormalities, including hippocampal atrophy, and a preliminary study has shown
      that an N-methyl-D-aspartate receptor antagonist may have antidepressant
      efficacy.

PMID- 11986992
TI  - Delayed pharmacological effects of antidepressants.
AB  - Although antidepressants may not be primary mood stabilizers, they are
      efficacious in the prophylaxis of recurrent depressive illnesses, as well as in
      the treatment of acute episodes. Pharmacological effects that may contribute to
      the prophylactic effects of these drugs are not understood. Studies have been
      carried out in which antidepressants have been given to laboratory animals, such
      as rats, for periods of up to 3-4 weeks. Data obtained in such studies are
      thought to be important for their beneficial effects in depressive episodes, but
      also may be relevant to their prophylactic effects. Results are presented showing
      that when selective inhibitors of serotonin or norepinephrine uptake are given
      for such time periods, they still produce selective effects on serotonergic or
      noradrenergic parameters. For example, long-term administration of selective
      norepinephrine reuptake inhibitors causes a down-regulation of beta(1)
      adrenoceptors. Selective serotonin reuptake inhibitors do not produce this
      effect. Long-term administration of selective serotonin reuptake inhibitors
      causes down-regulation of the serotonin transporter, but not the norepinephrine
      transporter. In contrast, selective norepinephrine reuptake inhibitors down
      regulate the norepinephrine transporter but not the serotonin transporter.
      Substantial loss of serotonin transporter binding sites takes 15 days to occur
      and is accompanied by a marked reduction of serotonin transporter function in
      vivo.

PMID- 11986993
TI  - Synaptic plasticity and mood disorders.
AB  - Recent studies demonstrate that the molecular elements known to regulate neuronal
      plasticity in models of learning and memory are also involved in the actions of
      drugs used for the treatment of depression and bipolar disorder. This includes up
      regulation of transcription factors, such as the cAMP response element binding
      protein and neurotrophic factors, such as brain derived neurotrophic factor.
      These findings raise the possibility that regulation of neural plasticity in
      specific neuronal circuits is integrally involved in the therapeutic intervention
      of mood disorders. Atypical antipsychotic drugs, including clozapine and
      olanzapine, are also effective for the treatment of bipolar disorder, and are
      used as add-on medication for unipolar depression. The possibility that these
      atypical antipsychotic drugs also influence the molecular determinants of
      synaptic plasticity that are involved in the response to drugs used for the
      treatment of mood disorders, is discussed.

PMID- 11986994
TI  - Mood stabilizers, glycogen synthase kinase-3beta and cell survival.
AB  - Glycogen synthase kinase-3beta (GSK3beta) is a central figure in many
      intracellular signaling systems and is directly regulated by lithium. Substantial
      evidence now indicates that an important property of the mood stabilizer,
      lithium, is to influence GSK3beta-linked signaling pathways. This raises the
      possibility that other mood stabilizers act in a similar manner, which may
      include modulation of signaling systems leading to GSK3beta, direct regulation of
      GSK3beta or regulation of signaling intermediates downstream of GSK3beta.
      Downstream targets of GSK3beta, and thus potential targets of mood stabilizers,
      are several key transcription factors, including beta-catenin, AP-1, cyclic AMP
      response element binding protein, NFkappaB, Myc, heat shock factor-1, nuclear
      factor of activated T-cells and CCAAT/enhancer-binding proteins. GSK3beta also is
      an important modulator of cell death, which may be a consequence of its
      regulatory effects on transcription factor activities. GSK3beta facilitates
      apoptosis, and lithium's inhibition of GSK3beta supports cell survival. Thus,
      signaling systems determining cell fate appear to be important targets of mood
      stabilizers, and these may include signaling pathways encompassing GSK3beta,
      including transcription factors regulated by GSK3beta.

PMID- 11986995
TI  - PKC, MAP kinases and the bcl-2 family of proteins as long-term targets for mood
      stabilizers.
AB  - The complexity of the unique biology of bipolar disorder--which includes the
      predisposition to episodic, and often progressive, mood disturbance--and the
      dynamic nature of compensatory processes in the brain, coupled with limitations
      in experimental design, have hindered our ability to identify the underlying
      pathophysiology of this fascinating neuropsychiatric disorder. Although we have
      yet to identify the specific abnormal genes in mood disorders, recent studies
      have implicated critical signal transduction pathways as being integral to the
      pathophysiology and treatment of bipolar disorder. In particular, a converging
      body of preclinical data has shown that chronic lithium and valproate, at
      therapeutically relevant concentrations, regulate the protein kinase C signaling
      cascade. This has led to the investigation of the antimanic efficacy of tamoxifen
      (at doses sufficient to inhibit protein kinase C), with very encouraging
      preliminary results. A growing body of data also suggests that impairments of
      neuroplasticity and cellular resilience may also underlie the pathophysiology of
      bipolar disorder. It is thus noteworthy that mood stabilizers, such as lithium
      and valproate, indirectly regulate a number of factors involved in cell survival
      pathways--including cAMP response element binding protein, brain derived
      neurotrophic factor, bcl-2 and mitogen-activated protein kinases--and may thus
      bring about some of their delayed long-term beneficial effects via under
      appreciated neurotrophic effects. The development of novel treatments, which more
      directly target molecules involved in critical central nervous system cell
      survival and cell death pathways, has the potential to enhance neuroplasticity
      and cellular resilience, thereby modulating the long-term course and trajectory
      of these devastating illnesses.

PMID- 11986996
TI  - Role of the cholinergic muscarinic system in bipolar disorder and related
      mechanism of action of antipsychotic agents.
AB  - The evidence for the involvement of cholinergic muscarinic receptors in mania and
      depression is reviewed. Small pilot trials with cholinesterase inhibitors and
      muscarinic agonists suggest that stimulation of muscarinic receptors may produce
      an antimanic effect, possibly by activation of muscarinic M(4) receptors. It is
      concluded that it is not likely that currently used mood stabilizers, such as
      lithium, valproic acid and carbamazepine, work directly through muscarinic
      receptor mechanisms. Furthermore, the evidence indicates that antipsychotic
      agents used for mania are working through the common mechanism of antagonism of
      dopamine D(2) receptors, and interactions with muscarinic receptors do not play a
      key role. Finally, it is hypothesized that olanzapine has robust antimanic
      activity, due to blockade of dopamine D(2) receptors and antagonism of other
      monoaminergic receptors. Olanzapine may normalize mood due to antidepressant-like
      activities, such as 5-HT(2A) receptor antagonism and increasing cortical
      norepinephrine and dopamine.

PMID- 11986997
TI  - Can brain-imaging studies provide a 'mood stabilizer signature?'.
AB  - Brain-imaging investigations have attempted to characterize the neurobiological
      basis of bipolar disorder. Preliminary studies have also focused on in vivo brain
      correlates of treatment response with antidepressants, mood stabilizers and other
      psychotropic medications. A MEDLINE literature search was conducted dating back
      to 1966. Selected in vivo brain-imaging studies that examined neurobiological
      correlates of treatment response in mood disorder patients were identified.
      Discrete anatomical abnormalities in subregions of the prefrontal cortex, medial
      temporal lobe and cerebellum have been identified in bipolar patients. Functional
      imaging studies suggested abnormalities in particular brain circuits encompassing
      these same brain regions and the striatum. However, functional imaging correlates
      of treatment response with lithium or other mood stabilizers have not yet been
      characterized. Neurochemical studies suggested a reduction in N-acetyl aspartate
      levels in prefrontal cortex and abnormalities in membrane phospholipids in
      frontal and temporal lobes. Preliminary findings suggest that lithium may
      increase the gray matter content and N-acetyl aspartate levels in various
      cortical regions, which could reflect its putative neurotrophic effects. Few in
      vivo receptor-imaging studies have examined brain correlates of treatment
      response in bipolar patients. The available studies suggest anatomical,
      neurochemical and functional brain abnormalities in bipolar patients. However, in
      vivo brain correlates of treatment response with mood stabilizers in bipolar
      patients have not yet been well characterized.

PMID- 11986998
TI  - Glutamate and GABA systems as targets for novel antidepressant and mood
      stabilizing treatments.
AB  - Glutamate and gamma-amino butyric acid (GABA) systems are emerging as targets for
      development of medications for mood disorders. There is increasing preclinical
      and clinical evidence that antidepressant drugs directly or indirectly reduce N
      methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic
      activity or glutamate receptor-related signal transduction may also have
      antimanic effects. Recent studies employing magnetic resonance spectroscopy also
      suggest that unipolar, but not bipolar, depression is associated with reductions
      in cortical GABA levels. Antidepressant and mood-stabilizing treatments also
      appear to raise cortical GABA levels and to ameliorate GABA deficits in patients
      with mood disorders. The preponderance of available evidence suggests that
      glutamatergic and GABAergic modulation may be an important property of available
      antidepressant and mood-stabilizing agents. Future research will be needed to
      develop and evaluate new agents with specific glutamate and GABA receptor targets
      in the treatment of mood disorders.

PMID- 11987003
TI  - Torture and its neurological sequelae.
AB  - BACKGROUND: Refugees and asylum seekers continue to enter the United States and
      the European Union in record numbers. Some have estimated that between 5-35% of
      all refugees have suffered torture in their countries of origin. Although general
      practitioners and specialized physicians are likely to encounter victims of
      torture as patients, few providers are familiar with the health problems that may
      affect this patient population. PURPOSE: :To provide neurologists, neurosurgeons,
      and rehabilitation medicine physicians with basic knowledge about survivors of
      torture that can help in the diagnosis, treatment, and referral of such patients.
      METHODS: A MEDLINE (1966-October 2001) search using keywords torture and sequelae
      (nervous system diseases and brain injuries) was conducted. Other data sources
      included books, reference lists, online resources and expert opinion. FINDINGS:
      :Forms of torture that may affect the nervous system include beatings, gunshot
      wounds, stab wounds, asphyxiation, prolonged suspension and electrocution.
      Victims of torture commonly experience neurological symptoms such as headaches,
      vertigo, loss of consciousness and dizziness during and after torture. A
      successful and meaningful clinical interaction with a survivor of torture
      includes avoiding retraumatization, building trust, spelling out any limits on
      confidentiality, and above anything else, establishing empathy with the patient.
      CONCLUSIONS: Neurological sequelae of torture can be devastating physically and
      psychologically. The treatment of these neurological conditions does not differ
      from other patient populations. However, the clinical approach is unique and must
      focus on avoiding retraumatization and helping the victim reintegrate into
      society as quickly as possible.

PMID- 11987004
TI  - Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal
      cord injury in rabbits.
AB  - STUDY DESIGN: Occlusion of the infrarenal abdominal aorta with administration of
      pentoxifylline was applied to adult rabbits, followed by removal of aortic clamp
      and reperfusion. Tissue levels of cytokines, lipid peroxides, and antioxidant
      enzymes were assayed and compared within groups. OBJECTIVES: To examine the
      effect of pentoxifylline (PTX) on cytokine levels, lipid peroxidation, and
      antioxidant enzymes in a rabbit model of spinal cord ischemia-reperfusion injury
      induced by aortic occlusion. SETTING: Isparta, Turkey. METHODS: Rabbits were
      randomly allocated into four groups of sham laparotomy (SHAM), sham laparotomy
      with PTX administration (SHAM+PTX), aortic occlusion and reperfusion (AOR),
      aortic occlusion and reperfusion with PTX administration (AOR+PTX). An
      intravenous bolus of 50 mg/kg PTX was given just before aortic cross clamping. An
      atraumatic microvascular clamp was then placed on the abdominal aorta immediately
      distal to the left renal artery for 30 min. PTX was infused at a rate of 0.5
      mg/kg/min during the aortic occlusion. Animals were subjected to 120 min of
      reperfusion after removal of the aortic clamp. All animals were sacrificed at the
      end of reperfusion. The lumbosacral segments of spinal cords were quickly
      harvested and stored at -78 degrees C for biochemical assays of IL-6, TNF-alpha,
      MDA, SOD, and CAT levels. Differences among groups were analyzed by one-way
      analysis of variance followed by a post hoc Tukey's honestly significant
      difference test. RESULTS: No differences in mean levels of IL-6, TNF-alpha, MDA,
      SOD, and CAT were noted between SHAM and SHAM+PTX groups (P>0.05). There was a
      significant increase in all biochemical parameters in the AOR group (P<0.05).
      Administration of PTX significantly attenuated the levels of all biochemical
      parameters in the AOR+PTX group (P<0.05). CONCLUSION: PTX pretreatment attenuated
      ischemia-reperfusion induced spinal cord injury in a rabbit model, in terms of
      biochemical parameters of ischemia and reperfusion.

PMID- 11987005
TI  - Intensive exercise may preserve bone mass of the upper limbs in spinal cord
      injured males but does not retard demineralisation of the lower body.
AB  - STUDY DESIGN: Cross-sectional study comparing a group of active spinal cord
      injured (SCI) males carefully matched for age, height, and weight with active
      able-bodied male controls. OBJECTIVES: To compare bone mass of the total body,
      upper and lower limbs, hip, and spine regions in active SCI and able-bodied
      individuals. SETTING: Outpatient study undertaken in two centres in New Zealand.
      METHODS: Dual energy X-ray absorptiometry (DEXA) scanning was used to determine
      bone mass. Questionnaires were used to ascertain total time spent in weekly
      physical activity for each individual. The criterion for entry into the study was
      regular participation in physical activity of more than 60 min per week, over and
      above that required for rehabilitation. RESULTS: Seventeen SCI and their able
      bodied controls met our required activity criterion. Bone mineral density (BMD)
      values of the total body and hip regions were significantly lower in the SCI
      group than in their controls (P=0.0001). Leg BMD and bone mineral content (BMC)
      were also significantly lower in the SCI group (P=0.0001). By contrast, lumbar
      spine BMD and arm BMD and BMC did not differ between the SCI and control groups.
      Arm BMD and BMC were greater (not significant) than the reference norms (LUNAR
      database) for both groups. CONCLUSION: Intensive exercise regimens may contribute
      to preservation of arm bone mass in SCI males, but does not prevent
      demineralisation in the lower body.

PMID- 11987006
TI  - The importance of posture on the isokinetic assessment of spasticity.
AB  - OBJECTIVE: To measure spasticity of the knee flexors and extensor muscles in two
      different hip positions. SETTING: Swiss Paraplegic Center Nottwil, Switzerland.
      METHODS: Twenty spinal cord injured (SCI) patients with complete lesions were
      tested with a torque-velocity dynamometer in the following positions: (1) supine
      with a hip angle of 0 degrees; (2) sitting with a hip angle of 90 degrees. The
      excursion of the knee was measured for both positions using a goniometer. Two
      flexion/extension movements of the knee were performed at a speed of 10 degrees
      per sec. A further four flexion/extension movements over the same trajectory were
      made at a speed of 120 degrees per sec. Eccentric peak torques were measured
      continuously during movement of both legs for both speeds. RESULTS: At a speed of
      120 degrees per second, there was a significant difference in stretch reflex of
      the hamstrings and quadriceps femoris muscles for the two positions (Wilcoxon's
      paired t-test, P<0.05). Excitability was higher for the quadriceps femoris
      muscles in supine than in sitting position. For the hamstrings, the effect was
      reversed. Significant differences between sitting and supine position were not
      found for the speed of 10 degrees per sec. Test-retest reliability was high for
      the movements of 120 degrees per sec but low for 10 degrees per sec. CONCLUSIONS:
      Our findings indicate that for a reliable and comparable measurement of
      spasticity, an exact description of test position and procedure is essential.

PMID- 11987007
TI  - Vertebral body infarction indicating midthoracic spinal stroke.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To illustrate the significance of vertebral
      body infarction as the only confirmatory sign of spinal cord ischemic stroke.
      SETTING: Department of Neurology, St. Josef-Hospital, Bochum, Germany. CASE
      DESCRIPTION: A 65-year-old man presented with clinical features suggesting
      spontaneous spinal cord infarction in the territory of the left sulcocommissural
      artery at the level of Th 8. Sequential magnetic resonance imaging (MRI)
      investigations failed to demonstrate infarction of the spinal cord but T2
      weighted images revealed bone marrow hyperintensities of vertebra Th 9 and 10 in
      their left and dorsal parts consistent with vertebral body infarction.
      CONCLUSION: In clinically presumed spontaneous spinal cord infarction and
      unremarkable signaling of the spinal cord during sequential MRI investigations
      vertebral body infarction may serve as the only confirmatory sign of spinal cord
      ischemic stroke.

PMID- 11987008
TI  - Destructive osteoblastoma of the cervical spine with complete neurologic
      recovery.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a patient with a large tumor
      lesion of the 6th vertebrae affecting surrounding soft tissue, and symptoms of
      cord compression. Histologic diagnosis indicated a destructive osteoblastoma
      following dorsal and anterior resection and internal fixation. SETTING:
      University Hospital, Germany. METHODS: A 23-year old male patient was admitted
      with a 2-month history of increasing upper extremity weakness and pain. X-ray and
      MRI indicated massive involvement of the anterior and posterior elements of the
      6th vertebrae with a large soft tissue mass. Following emergency decompression
      and dorsal stabilization, the pathologic investigation revealed a destructive
      osteoblastoma. Subsequent dorsal and anterior resection with internal fixation
      were performed. RESULTS: The patient initially presented with symptoms of
      beginning paraplegia of C6/7. According to the neurologic classification of
      spinal cord injury, motor function score was 56 and sensory function score 83.
      After emergency dorsal decompression and internal fixation with Luque
      Instrumentation he showed increasing neurological recovery. Complete neurological
      recovery was achieved at 2 and 12-months postoperatively, following secondary
      dorsal and anterior resection of the tumor and internal fixation with bone cement
      (PalacosR) and Harms-cage. Radiologic signs of local recurrence were identified 1
      year postoperatively. CONCLUSION: Osteoblastoma of the cervical spine is rare.
      Patients often present with severe neurological symptoms due to significant tumor
      mass. Complete resection is necessary to regain full recovery, to prevent
      recurrence and, in some cases, malignant transformation.

PMID- 11987009
TI  - Myelopathy and amnesia following accidental electrical injury.
AB  - OBJECTIVE: Documentation of MRI and neurophysiological changes following
      accidental electrical injury. SETTING: Tertiary care referral teaching hospital
      at Lucknow, India. RESULTS: A 30-year-old lady developed amnesia and spastic
      paraparesis with loss of pin prick sensation below the second thoracic spinal
      segment following electrocution. Her spinal MRI was normal and cranial MRI
      revealed T2 hyperintensity in the right putamen. Peroneal, sural and
      electromyography were normal. Tibial central sensory conduction time was normal
      but central motor conduction time to lower limbs and right upper limb was
      prolonged. CONCLUSION: Neurophysiological study and MRI may help in understanding
      the pathophysiological basis of neurological sequelae following electrical
      injury.

PMID- 11987010
TI  - Bone density scanning.

PMID- 11987014
TI  - [Primary prevention of type 2 diabetes].

PMID- 11987015
TI  - [Predictors of abnormal glucose tolerance in persons at risk of type 2 diabetes:
      the RIAD study].
AB  - BACKGROUND AND OBJECTIVE: Early detection of glucose intolerance is an important
      issue in diabetes care. In the metabolic syndrome it is associated with an
      increased incidence of cardiovascular events. So far it is not clear which
      anthropometric and metabolic/hormonal parameters are of importance in the
      conversion of normal to impaired glucose tolerance. PATIENTS AND METHODS: The
      participants of the RIAD (Risk factors in IGT for Atherosclerosis and Diabetes)
      study had to meet the following criteria: related to type 2 diabetic patients,
      obesity and/or dyslipidaemia. A total of 358 subjects (age: 40-70 years) with
      normal glucose tolerance (NGT) in an oral glucose tolerance test (OGTT, 75 g
      glucose), were examined after a follow-up of 2.90 +/- 0.47 years. 284 of them
      remained with normal glucose tolerance, while 64 developed an impaired glucose
      tolerance (IGT) and ten type 2 diabetes (T2DM). The data of the initial screening
      examination were analysed in three groups (NGT-NGT; NGT-IGT; NGT-T2DM). Plasma
      glucose (PG), insulin, C-peptide and proinsulin were measured in the fasting
      state, as well as every 30 minutes during an OGTT, and also basal plasminogen
      activator inhibitor (PAI) and inflammatory parameters. RESULTS: Subjects who
      converted to IGT or diabetes show, already in the stage of normal glucose
      tolerance, clear tendency for the development of the metabolic syndrome. They
      were more obese and had higher fasting and 2 hPG values. The early phase insulin
      secretion, calculated as a ratio of DeltaInsulin 30'/DeltaPG 30', was lower in
      the IGT and the diabetes groups (n. s.). Both groups showed a significantly
      increased insulin resistance. Both converter groups revealed significantly higher
      PAI (Plasminogen-Activator-Inhibitor) levels and a striking but not significant
      increase in inflammatory parameters. CONCLUSIONS: Subjects who develop IGT and
      type 2 diabetes, will already in the stage of NGT show an impairment of insulin
      secretion and higher insulin resistance. Both processes seem to develop parallel
      to each other and determine the progress of the glucose intolerance. Fasting and
      2h post-challenge glucose were the most important predictors of subsequent
      glucose intolerance.

PMID- 11987016
TI  - [Effect of glucose control on lipid levels in patients with type 2 diabetes].
AB  - BACKGROUND AND OBJECTIVE: The dyslipoproteinemia characterizing patients with
      type 2 diabetes is a major risk factor for atherosclerosis. Prospective studies
      indicate that an improved glucose control is associated with lower lipid levels.
      In this study we evaluated whether an improvement of the lipid status can also be
      observed in a routine clinical setting. Furthermore, we evaluated how many
      patients achieve lipid target levels by improving glucose control. METHODS: In 51
      type 2 diabetics (60 +/- 12 ys., 29 men, 22 women) lipid values were determined
      before and after improvement of glucose metabolism (6 - 12 weeks, HbA1c 7.9 +/-
      1.9 % vs. 7.1 +/- 1.3 %). Patients on lipid-lowering medication or with
      atherosclerosis were excluded. The improved glucose control was achieved by
      starting/intensifying treatment with diet (n = 5), acarbose (n = 5), metformin (n
      = 10), sulfonylurea/glinide (n = 12) or insulin (n = 19). RESULTS: The decrease
      in HbA1c was associated with a decrease in total cholesterol (232 +/- 64 vs. 216
      +/- 35 mg/dl, p < 0.05) and triglycerides (348 +/- 448 vs. 216 +/- 139 mg/dl, p <
      0.01), while HDL- and LDL-cholesterol did not change significantly. Only in
      patients with triglycerides > 200 mg/dl did changes in HbA1c-levels correlate
      with changes in triglyceride-levels (r(2) = 0.32, p = 0.012). Lipid target levels
      were reached in seven of 51 patients (five of 51 patients before improvement of
      HbA1c). CONCLUSION: Although in routine clinical practice an improvement in HbA1c
      results in better lipid values. This improvement is small and is usually not
      sufficient to reach lipid target levels.

PMID- 11987017
TI  - [Scintigraphic assessment of blood flow regulation and sympathetic function of
      the diabetic heart].

PMID- 11987018
TI  - [Polycystic ovary syndrome and metabolic syndrome].

PMID- 11987019
TI  - [Do we need new ways of cell and gene treatment of diabetics? - Pro].

PMID- 11987021
TI  - [Cost-effectiveness of screening in familial adenomatous polyposis].

PMID- 11987020
TI  - [Do we need new ways of cell and gene treatment of diabetics? - Contra].

PMID- 11987022
TI  - [Chronic lymphatic leukemia: significance of erythropoietin].

PMID- 11987023
TI  - [QT prolongation and torsade de pointes--tachycardia in therapy with
      maprotiline].

PMID- 11987025
TI  - Dietary modulation of circulating leptin levels: site-specific changes in fat
      deposition and ob mRNA expression.
AB  - In order to study the effects of diet on fat distribution, circulating leptin
      levels and ob mRNA expression, diets of different macronutrient composition were
      fed to lean mice and gold thioglucose-obese mice. A high-fat diet and 2 high
      carbohydrate diets, one containing mostly high-glycaemic-index starch and the
      other containing low-glycaemic-index starch were fed ad libitum for 10 weeks and
      were compared to standard laboratory chow. Weight gain was attenuated by feeding
      low-glycaemic-index starch in all mice and by feeding a high-fat diet in lean
      mice. Reduced adiposity was seen in lean mice fed low-glycaemic-index starch,
      whereas increased adiposity was seen in both lean and obese mice fed on the high
      fat diet. Circulating leptin levels, when corrected for adiposity, were decreased
      in all mice fed either the high-fat diet or the low-GI diet. In epididymal fat
      pads, decreased ob mRNA expression was seen after both high-fat and high
      glycaemic-index starch feeding. These results show that diet macronutrient
      composition contributes to the variability of circulating leptin levels by the
      combined effects of diet on fat distribution and on site-specific changes in ob
      mRNA expression.

PMID- 11987026
TI  - Metformin improves cardiac functional recovery after ischemia in rats.
AB  - The biguanide, metformin, is widely used for the treatment of type 2 diabetes
      mellitus. In the recently published United Kingdom Prospective Diabetes Study
      (UKPDS), it was shown that the use of metformin was associated with a reduction
      of macrovascular complications compared to other blood glucose-lowering
      strategies. The present study was aimed at determining whether metformin has
      direct beneficial effects on the heart. We tested the effects of metformin on
      cardiac functional recovery after a mild ischemic incident (stunning) in our
      isolated, erythrocyte perfused, rat working-heart model. Three groups were
      tested: vehicle, 50 and 500 micromol/l metformin (total n = 6). In diabetic rats,
      a concentration of 50 microM has been shown to reduce the blood glucose
      concentration. Slight metformin-induced increases in coronary blood flow during
      normoxia (pre-ischemically) and during reperfusion (post-ischemically) were
      observed and compared to vehicle (p < 0.05). Both metformin concentrations
      significantly reduced cardiac functional loss induced by the 12-min global
      ischemic incident compared with vehicle (3.4 +/- 1.0 % and 3.5 +/- 0.6 % loss
      during metformin versus 10.7 +/- 0.8 % during vehicle, p < 0.001). This study
      clearly shows that metformin acutely improves cardiac function after a mild
      ischemic incident (stunning) in rats.

PMID- 11987027
TI  - IA-2 autoantibodies restricted to the IgG4 subclass are associated with
      protection from type 1 diabetes.
AB  - The tyrosine phosphatase-like protein IA-2 is a major target antigen for
      autoantibodies in the preclinical period of type 1 diabetes. In this study, we
      examined whether immunoglobulin isotypes and IgG subclass specific autoantibodies
      directed at IA-2 discriminate between children at risk of type 1 diabetes who
      progressed to diabetes vs. those who remained diabetes-free. IgG1-4, IgA and the
      IgE-specific IA-2 antibody (IA-2A) were measured by radioligand assays in 50
      patients with type 1 diabetes and 41 ICA-positive siblings of patients with type
      1 diabetes who were followed for diabetes development. Of 41 siblings, 32 were
      positive for IA-2A; of these, 59 % had IA-2 IgG1, 59 % IgG4, 16 % IgG3, 9 % IgG2,
      16 % IgA and 13 % IgE antibodies. IA-2 IgG1 was the dominant isotype in
      prediabetic children (n = 14, 86 % positive) and patients with type 1 diabetes
      (98 % positive) whereas only 7 of 18 (39 %) non-progressors had antibodies of
      this isotype. In subjects that remained diabetes-free, a significantly higher
      frequency of IA-2 IgG4 in the absence of IgG1 was observed (50 %) compared to
      progressors (7 %) and patients with type 1 diabetes (0 %). Life-table analysis
      revealed that IA-2A restricted to IgG4 correlated with protection from type 1
      diabetes (p < 0.003). In contrast, IA-2 IgG2, IgG3, IgE and IgA did not differ
      significantly between study groups. Our findings suggest that the measurement of
      IA-2 IgG1 and IgG4 subclass antibodies can serve as surrogate marker to
      discriminate between antibody positive subjects at high or low risk for rapid
      development of diabetes.

PMID- 11987028
TI  - General screening for celiac disease is advisable in children with type 1
      diabetes.
AB  - The association between celiac disease (CD) and diabetes mellitus type 1 is well
      known. Only about one-third of all patients with CD are diagnosed in childhood as
      a result of typical gastrointestinal symptoms or growth retardation. To evaluate
      the feasibility of CD screening in diabetic children, we tested autoantibodies to
      tissue transglutaminase (tTGA) in all children with type 1 diabetes from our
      pediatric department during a 12-month period. In antibody-positive cases, we
      analyzed the clinical presentation and offered a duodenal biopsy to confirm the
      diagnosis and grade the severity of the inflammatory process. Of 205 children, 13
      (6.3 %) were tTGA-positive. In seven of eight children who agreed to perform a
      biopsy, CD typical histological signs were detected (Marsh 1: n = 1, Marsh 3: n =
      6). In three patients with confirmed disease, symptoms (iron deficiency,
      recurrent abdominal pain) remained undiscovered up to time of screening (latent
      form); in four, the disease was asymptomatic (silent form). Since clinical
      symptoms are mostly mild or absent in spite of severe signs of duodenal
      inflammation, we recommend tTGA screening in all diabetic children. This strategy
      may allow the identification of patients in an early stage in respect of
      prevention of long-term complications.

PMID- 11987029
TI  - Soluble LDL-immune complexes in type 2 diabetes and vascular disease.
AB  - BACKGROUND AND AIMS: The oxidative modification of LDL has been shown to affect
      its clearance and to exert cytotoxic and immunogenic effects. The objective of
      our study was to analyse markers of LDL oxidation-soluble LDL containing immune
      complexes (LDL-ICs) in type 2 diabetes with micro- and macrovascular disease.
      PATIENTS AND METHODS: The study included 69 diabetic patients with coronary
      artery disease (DM + CAD), 78 non-diabetics with CAD, 47 controls, and 27
      diabetics with nephropathy and 36 free from complications. OxLDL antibodies and
      advanced glycated end-products were measured by ELISA, and LDL-IC apo B content
      after PEG precipitation. RESULTS: Determination of a broad range of oxLDL
      antibody activity in all study groups showed no significant differences. In
      contrast, the content of apo B, a component of the antigen moiety of oxLDL-ICs,
      was higher in CAD and diabetes (+ CAD) than in LDL-ICs isolated from controls (p
      < 0.001). LDL-ICs did not differ between patients with CAD + DM and CAD patients
      free from diabetes. LDL-IC levels in diabetic patients with or without
      microangiopathy were significantly higher than in healthy volunteers (PEG-apo B
      0.278 +/- 0.107 vs. 0.165 +/- 105 g/l, p < 0.002; PEG-IgG 151.7 +/- 76 vs. 115.4
      +/- 62 g/l, p < 0.05). However, there was no significant difference in the level
      of circulating LDL-ICs between the subgroup of diabetic patients with
      nephropathy/retinopathy and patients free of microvascular disease (Ab-oxLDL 27.7
      +/- 10.4 vs. 27.1 +/- 9.3 AU, NS; PEG-apo B 0.324 +/- 0.111 vs. 0.287 +/- 0.124
      g/l, NS; PEG-IgG 1.68 +/- 0.68 vs. 1.42 +/- 0.80 g/l, NS). There was a
      statistically significant positive correlation between AGE content and LDL-ICs (r
      = 0.35, p < 0.009). A significant but inverse correlation was recorded between
      triglyceride concentration and level of LDL-ICs in DM + CAD (r = - 0.32, p <
      0.016) and CAD patients (r = - 0.35, p < 0.002). A highly significant negative
      correlation between triglycerides and circulating LDL-ICs (r = - 0.54, p < 0.039)
      was observed in patients with early nephropathy, but not in those with
      physiological proteinuria. It is known that at a high triglyceride level in type
      2 diabetes, the majority of LDL are small and dense, thus being more susceptible
      to oxidative modification. This could be a possible mechanism explaining why more
      LDL-ICs, with a level inversely correlating with triglyceride concentration, are
      generated in diabetes. CONCLUSION: The increased level of circulating LDL-ICs is
      a risk factor for the general population, including those with diabetes. Our
      results suggested the contribution of LDL-ICs to the development of
      atherosclerosis to probably be more significant than the direct contribution of
      oxLDLAb itself.

PMID- 11987030
TI  - Molecular and biochemical screening for the diagnosis and management of medullary
      thyroid carcinoma in multiple endocrine neoplasia type 2A.
AB  - Patients with Multiple Endocrine Neoplasia (MEN) type 2A are at risk for early
      medullary thyroid carcinoma (MTC). We performed different screening tests for MTC
      -a recently reported biochemical screening test using omeprazole-induced
      calcitonin (CT) stimulation and DNA analysis--in fifteen members of two non
      consanguineous Brazilian families with MEN 2A. RET proto-oncogene analysis was
      carried out by direct DNA sequencing of PCR-amplified products for exons 10 and
      11. Family 1 showed a germline mutation (C634Y) in three individuals; a sister
      and a brother with symptomatic MTC; the former also presented with
      pheochromocytoma and hyperparathyroidism, and her son was a nine-year-old boy of
      previously unknown status. Family 2 showed the C634R mutation only in the index
      case, who presented with cutaneous lichen amyloidosis in addition to MTC,
      pheochromocytoma and hyperparathyroidism. Neither her parents nor her four
      brothers showed this genetic abnormality, suggesting a de novo RET proto-oncogene
      mutation in this patient. The controls and patients presented normal basal
      gastrin levels and a significant increase after omeprazole. Basal CT levels were
      elevated in patients with MTC and undetectable in control and asymptomatic family
      members. No subject showed any increase in CT levels after omeprazole treatment.
      In conclusion, the two most frequent RET proto-oncogene mutations in MEN 2A are
      present in Brazilian families. In addition, the specificity of basal and
      omeprazole-stimulated calcitonin is rather limited, and the efficacy of the
      omeprazole test still needs to be systematically examined. Therefore, RET proto
      oncogene analysis must be the first choice for a screening procedure to identify
      gene carriers in MEN 2A family members and to permit early prophylactic treatment
      of MTC.

PMID- 11987031
TI  - The opposite effects of short- and long-term salt loading on pituitary adrenal
      axis activity in rats.
AB  - Osmotic stimulation has been shown to modify corticotropin responsiveness. We
      compared the effects of short- and long-term salt loading on pituitary-adrenal
      activity in control rats receiving tap water and rats submitted to salt loading
      for 1 day (S1) or 8 days (S8). Corticosterone (B) and adrenocorticotropic hormone
      (ACTH) plasma levels were determined at 8 a. m. under basal conditions or after
      immobilization stress for 15 min or corticotropin-releasing hormone (CRH)
      stimulation. S1 rats showed a similar ACTH response to immobilization, but an
      increased CRH response. In contrast, S8 rats showed blunted responses after
      immobilization or CRH stimulation. To evaluate the circadian variation of this
      inhibitory effect on the stress in the S8 group, immobilization was also
      performed at 8 p. m. Plasma ACTH and B levels under resting conditions were
      higher at 8 p. m. than 8 a. m. (p < 0.05) in control and S8 rats. The ACTH
      response to immobilization in the S8 group was lower than control at both 8 a. m.
      and 8 p. m. (p < 0.05); however, this reduction was more evident the morning,
      resulting in an inversion of the diurnal pattern with a higher ACTH response at 8
      p. m. In conclusion, short osmotic stimulation results in an increased pituitary
      response to CRH, whereas prolonged stimulation decreases the pituitary response
      to CRH and immobilization, showing an interaction between osmoregulation and
      hypothalamus-pituitary-adrenocortical activity.

PMID- 11987032
TI  - Association between maternal and child leptin levels 9 years after pregnancy
      complicated by gestational diabetes.
AB  - Obesity is a state of relative leptin resistance, and obesity in childhood is
      associated with an increased incidence of type 2 diabetes in later life.
      Offspring of mothers with gestational diabetes mellitus (GDM) are at increased
      risk of obesity. A cohort consisting of 64 mothers, 33 GDM and 31 controls
      screened for diabetes during the index pregnancy together with their 9-year-old
      offspring were studied. Our hypotheses were: 1) an elevated child leptin is
      associated with elevated maternal leptin in GDM mothers 9 years post delivery;
      and 2) child leptin at 9 years serves as a marker for incipient insulin
      resistance. By univariate analyses, child leptins were only significantly
      correlated with maternal leptins among the offspring of GDMs (OGDM) (r = 0.59; p
      = 0.001). By multivariate analyses, child leptin for the total study group was
      significantly associated with child body mass index (BMI) (R(2) = 0.65; p <
      0.0001), child fasting insulin (R(2) = 0.08; p = 0.03), and female gender (R(2) =
      0.28; p = 0.001). In addition, among OGDM child leptin was associated with
      maternal leptin (R(2) = 0.14; p = 0.005). Our results suggest that there is an
      association between maternal and child leptin levels 9 years after a pregnancy
      complicated by gestational diabetes.

PMID- 11987033
TI  - Normalization of cytoplasmic calcium response in pancreatic beta-cells of
      spontaneously diabetic GK rat by the treatment with T-1095, a specific inhibitor
      of renal Na+-glucose co-transporters.
AB  - Chronic hyperglycemia is known to lead to a progressively further impaired
      insulin response and to hasten the development of complications in patients with
      type 2 diabetes, a notion referred as glucose toxicity. T-1095, a derivative of
      phlorizin, is a newly developed oral hypoglycemic agent that acts as a specific
      inhibitor of renal Na(+)-glucose co-transporters, reducing circulating blood
      glucose levels by promoting glucose excretion into urine. The effects of glycemic
      improvement by T-1095 on secretory function and cytoplasmic calcium response in
      pancreatic beta-cells were investigated using spontaneously diabetic GK rats.
      After four weeks of treatment with T-1095 (age 4 to 8 week rats), serum glucose
      and HbA1c levels were significantly improved (serum glucose level, GK vs. GK T
      1095, 277.3 +/- 11.8 vs. 204.7 +/- 6.4 mg/dl; HbA1c level, GK vs. GK T-1095, 6.2
      +/- 0.2 vs. 4.8 +/- 0.1 %). Insulin secretion induced by 16.7 mM glucose was also
      significantly increased in the T-1095-treated group compared to the untreated
      group. The [Ca(2+)]i response induced by 16.7 mM glucose in GK beta-cells was
      characterized by the loss of the steep first peak of [Ca(2+)]i elevation, and the
      lost first peak of [Ca(2+)]i reappeared in T-1095-treated beta-cells in 32 of 34
      observations. In T-1095-treated beta-cells, the time lag to peak [Ca(2+)]i levels
      in the 16.7 mM glucose stimulation was significantly reduced (259.1 +/- 15.3 sec,
      p < 0.01) compared to untreated GK rats (524.7 +/- 52.9 sec). Thus, improvement
      of hyperglycemia by T-1095 ameliorates beta-cell function by relieving [Ca(2+)]i
      response.

PMID- 11987034
TI  - [Ultrasound biomicroscopy in eyelid lesions - a clinical study on 30 patients].
AB  - BACKGROUND: The value of ultrasound biomicroscopy in the diagnosis of eyelid
      lesions is not well known. METHODS: For the examination of eyelid lesions, we
      used an ultrasound biomicroscope (Humphrey, Zeiss, Oberkochen) with high
      frequency transducers (30 and 50 MHz). Between November 1998 and December 1999,
      30 patients with eyelid lesions, range 8 to 86 years, were available for this
      study. RESULTS: Histological examination of the excised tissue displayed the
      presence of chalazion (9/30), basal cell carcinoma (7/30), seborrhoic keratosis
      (4/30), a granulomatous process (4/30), cysts (2/30), an epidermoid cyst (1/30),
      a nevus (1/30), a pilomatrixoma (1/30), and a comedo (1/30). With ultrasound
      biomicroscopy we were able to demonstrate a cyst or a cystic tumour in six
      patients (20 %); i. e. two patients with a cyst of the eyelid, two patients with
      chalazion, one patient with a granulomatous process and one patient with an
      epidermoid cyst. In the patients with solid tumours of the eyelid, final
      diagnosis with ultrasound biomicroscopy only is not possible. CONCLUSION: For
      evaluation of cystic or solid eyelid lesions, ultrasound biomicroscopy may be an
      additional diagnostic tool, e. g. for assessment of the margins of the tumour.
      However, up to now it is not possible to differentiate tumours if only ultrasound
      biomicroscopic findings are available.

PMID- 11987035
TI  - [The effect of retrobulbar anaesthesia on visual evoked responses].
AB  - BACKGROUND: Retrobulbar anaesthesia in ocular surgery leads to a temporary
      sensory blockade of the nervus opticus. The purpose of this study was to
      investigate the effect and duration of this anaesthesia on the visual system and
      to find out whether there is any relation to the patient's age, oral
      premedication, time of oculopression and the axial length of the operated eye.
      MATERIALS AND METHODS: A total of 57 patients with a mean age of 77.4 +/- 9.5
      years were included in the study. All patients received retrobulbar injection of
      4cc Xylonest(R) 2 %/Dur-Anest(R) 1 % (3 : 1). Visual evoked potential (VEP) was
      recorded before and shortly after retrobulbar anaesthesia and several times after
      cataract surgery (45 min to 6 hours after surgery). The latency period and
      amplitude of the P100 deflection of the VEP were analysed. A possible correlation
      to the above-mentioned variables was evaluated statistically. RESULTS: Directly
      after retrobulbar injection of the anaesthetic and at the first postoperative VEP
      recordings the VEP recordings showed a decreased amplitude and an increased
      latency period. All measured values returned to normal within 2 hours after the
      retrobulbar injection, proving that the conductivity block of the optic nerve was
      temporary. There was a poor correlation between patients' age, ocular length of
      the operated eye and the degree of reduction of the recorded VEP. No correlation
      could be found between time of oculopression, premedication and the alteration of
      the VEP. CONCLUSION: Retrobulbar anaesthesia with 4cc of a mixture of
      Xylocain/Dur-Anest leads to a temporary conductivity block in the optic nerve for
      about 2 hours.

PMID- 11987036
TI  - [Enterococcal endophthalmitis following cataract surgery].
AB  - BACKGROUND: Postoperative endophthalmitis can be subdivided into acute and
      chronic forms which are typically caused by different organisms. Enterococcus
      faecalis is an organism which normally causes an acute form of endophthalmitis.
      PATIENTS AND METHODS: We report on four cases of different forms of
      endophthalmitis following cataract extraction and intraocular lens (IOL)
      implantation who had been referred to our institution between 1998 and 2001.
      Enterococcus faecalis was the causative organism in all of them. RESULTS: Two
      patients presented with an acute form and were immediately treated in our
      hospital after symptom onset utilizing pars plana vitrectomy with and without IOL
      explantation. The two other patients were initially treated with subconjunctival
      and/or systemic antibiotics and steroids over a period of about two months before
      referral to our hospital. After initial improvement the inflammation exacerbated
      in these two patients and vitrectomy with or without IOL and capsular bag
      explantation was performed. The explanted IOL and capsular bag of one patient
      were examined using scanning electron microscopy and it was shown that the
      enterococci were adherent to the IOL and the capsular bag. CONCLUSION:
      Enterococcus faecalis can be the causative organism both of an acute and of a
      recurrent form of postoperative endophthalmitis. The recurrent form may be caused
      by organisms which tend to adhere to the IOL and the capsular bag. This should be
      kept in mind when considering different treatment options.

PMID- 11987037
TI  - [Health Economical Evaluation of antibiotic prophylaxis against postoperative
      endophthalmitis].
AB  - BACKGROUND: Two independent epidemiological studies recently suggested the
      prophylactic relevance of an intraocular antibiosis against endophthalmitis after
      cataract surgery. The resulting intervention programme, however, has not only
      ethical drawbacks, but also has a health economical dimension, which will be
      focussed in this paper. MATERIAL AND METHODS: A cost analysis is performed to
      compare the direct costs saved by prevention of endophthalmitis cases and the
      costs generated by the prophylaxis itself. Furthermore, the clinics' indirect
      costs due to treatment of unprevented endophthalmitis cases are estimated.
      RESULTS: The overall gain in direct costs turns out to be about 368 000 Euro p.
      a., the indirect costs from the clinics' view can be reduced by about 260 000
      Euro p. a. due to prevention of endophthalmitis cases by the antibiotic
      intervention. CONCLUSIONS: From an economical point of view, antibiotic
      prophylaxis can be suggested; the risk of longitudinally reduced antibiotic
      effectiveness of the antibiotic agents, however, strongly calls for an overall
      health political decision rather than for an immediate implementation of the
      corresponding intervention programme.

PMID- 11987038
TI  - [Extracapsular cataract surgery with posterior chamber lens implantation in
      patients with diabetes mellitus - retrospective study on 145 patients].
AB  - BACKGROUND: The purpose of this paper is to investigate whether cataract surgery
      in patients with diabetes mellitus influences the progression of diabetic
      retinopathy, diabetic macular oedema and anterior segment complications. PATIENTS
      AND METHODS: 145 consecutive patients with type-II-diabetes mellitus underwent an
      extracapsular cataract surgery with implantation of a posterior chamber lens. 88
      patients (119 eyes have been operated) could be followed up for an average of 19
      months and 58 patients (88 eyes have been operated) could be followed up for an
      average of 38 months. Evaluation of the data included the preoperative retinal
      findings, intraoperative and early postoperative complications and problems, the
      progression of diabetic fundus changes, the progression of visual acuity and late
      complications. RESULTS: Insufficient pupil dilatation (25.2 %) was the most
      frequent intraoperative complication. Among early postoperative complications
      anterior segment inflammation was most frequent (10.1 %). During the follow-up
      period the diabetic retinopathy in the operated eyes showed a progression which
      was statistically not different from that in the non-operated eyes. After an
      average of 19 months the diabetic retinopathy deteriorated in 22.7 % of the
      operated eyes and in 17.5 % of the non-operated eyes. After an average of 38
      months the diabetic retinopathy deteriorated in additional 12.5 % of the operated
      and 11.1 % of the not-operated eyes. A diabetic macular oedema was present after
      an average of 19 months in 6.8 % of the operated 119 eyes and after an average of
      38 months in 6.7 % of the operated 88 eyes. In the non-operated partner-eyes no
      diabetic macular edema developed during the follow-up period. The main late
      complication during the whole follow-up period was the development of a capsular
      fibrosis in 52.3 % of the operated eyes. Postoperative visual acuity at the end
      of the first follow-up period (average 19 months) was >/= 0.5 in 85.7 % of the
      operated eyes and at the end of the second follow-up period (average 38 months)
      in 81.8 % of the operated eyes. CONCLUSION: Extracapsular cataract surgery in
      patients with diabetes mellitus is a procedure with good results, of high
      reliability and a slightly higher rate of complications than in non-diabetic
      patients. Extracapsular cataract surgery does not give rise to progression of
      diabetic retinopathy.

PMID- 11987039
TI  - [Topical Fk506 in inflammatory corneal and conjunctival diseases. A pilot study].
AB  - BACKGROUND: Topical corticosteroids are the only effective measure in serious
      inflammatory corneal and conjunctival diseases. Although results obtained with
      topical cyclosporin A are encuraging it is not effective in all patients. The
      mode of action of Fk506 is similar to that of cyclosporin A, i.e. it exerts an
      inhibitory effect on transcription of interleukin 2 in T lymphocytes. The
      immunosuppressive potential of Fk506, however, is much larger. Furthermore, it
      penetrates more easily into cornea and conjunctiva. To find out whether the
      theoretical advantages of topical Fk506 can be translated into clinical practice,
      a selected group of patients refractory to conventional therapy was treated in
      this pilot study. PATIENTS AND METHODS: Fk506 0.06 % was administered initially
      three times daily in 15 patients with atopic blepharokeratoconjunctivitis,
      Mooren's ulcer, ocular pemphigoid, Thygeson's superficial punctate keratitis,
      nummular adenoviral keratitis, graft-versus-host reaction of the conjunctiva and
      steroid response glaucoma after penetrating keratoplasty. RESULTS: Within a
      follow-up of 26 +/- 15 weeks improvement was recorded in 5/15 patients and
      stabilization in 5/15 patients. In two patients progression of the disease was
      noted (one patient with progression of ocular pemphigoid, another patient with
      suspected automutilation). Premature withdrawal the drug was judged to be
      necessary in two patients with ocular surface disorders and in one patient with
      non-compliance. CONCLUSIONS: Topical Fk506 seems to be a promising new
      immunosuppressive drug for patients with atopic blepharokeratoconjunctivitis,
      Thygeson's superficial punctate keratitis and nummular adenoviral keratitis.
      Exact efficacy in these and other corneal and conjunctival inflammatory diseases
      has to be determined in randomised clinical studies. Before these studies may
      start the risk of side-effects must be reduced via an improvement of the drops.

PMID- 11987040
TI  - [Impact of cataract surgery on intraocular pressure after filtering operation due
      to primary open angle glaucoma and secondary glaucoma in pseudoexfoliation
      syndrome].
AB  - PURPOSE: To analyse the impact of cataract surgery after filtering operation on
      the intraocular pressure (IOP) due to primary open angle glaucoma (pOAG) versus
      secondary open angle glaucoma in pseudoexfoliation syndrome (PEX). The regulation
      of IOP was evaluated on the basis of criteria of advanced glaucoma intervention
      study (AGIS). PATIENTS AND METHODS: Retrospectively 95 eyes of 95 patients (53 x
      pOAG, 36 x clear cornea approach [group 1] and 17 x corneoscleral tunnel [group
      2]; 42 x PEX, 30 x clear cornea approach [group 3] and 12 x corneoscleral tunnel
      [group 4]) were included. The IOP and antiglaucomatous eye drops were analysed
      before filtering operation, before cataract surgery and on average 33 months
      after cataract surgery. RESULTS: In all groups there was a significant reduction
      of IOP after filtering operation by 8.7 mm Hg on average and no significant
      difference of IOP before and after cataract surgery. At no time there was a
      significant difference in IOP between the four subgroups. According to criteria
      of the AGIS study 34 % of group 1, 29 % of group 2, 36 % of group 3 and 17 % of
      group 4 had an IOP lower than 14 mm Hg before cataract surgery. After cataract
      surgery only 31 % of group 1, 18 % of group 2, 13 % of group 3 and 8 % of group 4
      met this criterion. CONCLUSION: On first glance sequential cataract surgery after
      filtering operation seems to have no clinically relevant impact on the IOP,
      neither with regard to the type of glaucoma nor in respect of the approach for
      cataract surgery. However, if IOP is evaluated based on the criteria of the AGIS,
      primary open angle glaucoma with clear cornea approach appears to yield superior
      results in contrast to secondary open angle glaucoma in pseudoexfoliation
      syndrome with corneoscleral tunnel concerning the regulation of intraocular
      pressure.

PMID- 11987041
TI  - [Measurement of intraocular pressure using the Tono-Pen in comparison with
      Goldmann applanation tonometry - a clinical study in 100 eyes].
AB  - BACKGROUND: In clinical practice ophthalmologists often need a tonometer which is
      independent of a slit lamp. Such a hand-held device is the Tono-Pen. We compared
      the precision of two equal Tono-Pens with Goldmann applanation tonometry.
      MATERIAL AND METHODS: Measurement of intraocular pressure (IOP) was done in 100
      eyes of 51 patients (mean age 63 +/- 15 years) suffering from ocular hypertension
      or glaucoma. According to a random table either the right or left eye was
      measured using Goldmann tonometer first and the Tono-Pen second. For the other
      eye the measurement was reversed. One of the two equal Tono-Pens (Solan/USA) was
      used according to a second random table. Three measurements were obtained with
      each instrument on both eyes within 15 minutes subsequently. Patients were placed
      in an upright position for all measurements. RESULTS: Even for well-trained
      ophthalmologists a learning curve of approximately 10 measurements was observed
      using the Tono-Pen. The Tono-Pen measured an average IOP of 16.9 mm Hg in all 100
      eyes. The Goldmann tonometer measured an average IOP of 17.7 mm Hg. The
      difference was not statistically significant. The standard deviation for all
      measurements was better for the Tono-Pen (4.7 mm Hg vs 5.8 mm Hg for Goldmann
      tonometer). No reduction of the IOP after Tono-Pen measurement was observed (in
      contrast to the Goldmann tonometer). The reproducibility of the Tono-Pen on the
      same eye was inferior to the Goldmann tonometer by a factor of 2. There was an
      almost significant difference in reproducibility between two equal Tono-Pens.
      CONCLUSIONS: Measurement of IOP with the Tono-Pen is comparable to Goldmann
      applanation tonometry if an average of 3 measurements is used. The difference
      between two equal Tono-Pens indicates the need for improvement of the quality
      check during production.

PMID- 11987042
TI  - [Standard designs of epidemiological studies and their characteristics in
      ophthalmology].
AB  - This text gives an overview on standard epidemiological study designs and their
      main advantages and limitations concerning clinical and economical aspects, of
      performance. Ophthalmological examples are used to illustrate the design
      characteristics of cross-sectional, cohort and case control studies. These
      designs are compared by the fictitious planning of an epidemiological study to
      assess the prophylactical relevance of intraocular antibiotics against post
      cataract endophthalmitis; general practical hints for the designing of
      epidemiological studies are given.

PMID- 11987043
TI  - [Vision 2020: 100 years of river blindness research].
AB  - BACKGROUND: The early investigators of onchocerciasis from 1874 - 1930 in Africa
      made no mention at all of concomitant severe eye disease. Publications of the
      observations in Central America in 1917/1919 prompted some specialists in
      tropical medicine to look for eye disease associated with African onchocerciasis.
      However, there did not seem to be any eye disease leading to blindness. It was
      not until 1930/1931 that Hissette reported that 20 % of patients with
      onchocerciasis were blind in an onchocerciasis focus on the Sankuru river in the
      Belgian Congo, and that 50 % of the villagers suffered from eye troubles. Two
      years later, he found a second focus with the same pathology on the Uele river.
      WORKING HYPOTHESIS: We wished to establish why African river blindness manifested
      itself so unusually late and what criteria must be fulfilled for it to be brought
      under control quickly. The following questions are examined: (1) Had the early
      tropical doctors overlooked river blindness? (2) Could the still low distribution
      and density of microfilariae in the body of the affected patients have determined
      whether or not eye disease is likely to occur? (3) Had the microfilariae mutated
      into a more aggressive variety? RESULTS: There are indications confirming all
      three points in the working hypothesis. Before 1930, cases of African
      onchocerciasis with ocular complications were demonstrably very localized on the
      Uele river. The reason for this is likely to have been that the severity of the
      disease still varied from focus to focus at that time and/or because the
      individuals concerned still had a relatively mild microfilarial infection.
      CONCLUSION: In principle, onchocerciasis has reverted to the situation before
      occurrence of ocular complications in consequence of the ongoing control measures
      even though the insect destruction and mass therapy are sometimes incomplete.
      This appears to be sufficient to prevent blindness even if onchocerciasis is not
      cured. Only a few of the present-day patients with river blindness will still be
      left by 2030. By then, the problem of river blindness is likely to have become a
      thing of the past.

PMID- 11987044
TI  - [Ligneous conjunctivitis in a patient with plasminogen type I deficiency--case
      report with review of literature].
AB  - BACKGROUND: Ligneous conjunctivitis is a rare chronic pseudomembranous
      conjunctivitis. It forms nodular masses on the palpebral conjunctiva. Beside the
      conjunctival affection pseudomembranes can also be found on other mucosal
      tissues. PATIENT: We report on a male baby who had a ventriculoperitoneal shunt
      due to hydrocephalus internus on his fourth day after birth. Recurrent
      pseudomebranous conjunctivitis started in the first week of life. This was
      refractory to drug therapy and reoccurred soon after surgical procedure. The
      analysis of clotting parameters revealed homozygous plasminogen deficiency.
      CONCLUSION: Recently type I plasminogen deficiency seems to be a major reason for
      developing conjunctivitis lignosa. Homozygous and heterozygous mutations in the
      plasminogen gene are found. At the moment no satisfactory therapy is available.
      Cases with mild ophthalmological symptoms seem to be positively influenced by a
      therapy of topical steroids combined with heparin. In severe cases with
      generalised symptoms systemic therapy with lys-plasminogen is necessary. High
      costs and poor bioavailability complicate systemic therapy. Improved plasminogen
      variants for treatment of severe type I plasminogen deficiency would be of great
      clinical importance.

PMID- 11987045
TI  - [Implantation of an ARTISANtrade mark toric phakic intraocular lens to correct
      high astigmatism after penetrating keratoplasty].
AB  - BACKGROUND: Visual outcome after penetrating keratoplasty is often Iimited by
      residual astigmatism. Sometimes conservative treatment modalities like glasses or
      contact lenses fail to correct the keratoplasty-associated astigmatism.
      Refractive options are arcuate keratotomy, photorefractive keratectomy or laser
      in situ keratomileusis. The implantation of an ARTISAN toric intraocular lens
      presents an additive option to correct corneal astigmatism in phakic eyes. This
      toric intraocular lens (IOL) has an optical zone of 5.0 mm with a sphericaI front
      and a toric back. The torus of the IOL is available up to 7 D in half dioper
      steps. CASE REPORT: A 27-year old female presented with a bestcorrected visual
      acuity of 20/32. Penetrating keratoplasty was performed in 1997 because of a
      decompensated keratoconus. Despite a clear allgraft visual acuity was limited
      because of a keratoplasty-related high astigmatism of 7.6 D/124 degrees, which
      could not be sucessfully treated with glasses or contact lenses. An ARTISAN toric
      intraocular lens with - 3 D spherical and 7.0 D/0 degrees cylindrical power
      (individually manufactured) was implanted via a sclerocorneal tunnel incision
      into the anterior chamber. Postoperatively an optimal graft clarity with a well
      centered and stable-positioned IOL was found. After 3 months uncorrected visual
      acuity was 20/25. Six months after implantation the IOL was still well-centered
      and uncorrected visual acuity was 20/20. CONCLUSION: Implantation of an ARTISAN
      toric intraocular lens in phakic eyes is an alternative and new option to correct
      higher astigmatism. In contrast to the keratorefractive option minor manipulation
      on the allograft can be expected. For a final conclusion of the endothelial cell
      loss longer follow-up is necessary.

PMID- 11987046
TI  - [Nocardia farcinica: life-threatening chorioiditis under systemic
      immunosuppression].
AB  - BACKGROUND: Immunosuppressed patients occasionally suffer from a multifocal
      infection with Nocardia. It is important to distinguish Nocardia farcinica from
      Nocardia asteroides, because of different sensitivity against antibiotics.
      PATIENT AND METHODS: A 40-year-old patient with polycystic renal disease
      successfully underwent a kidney transplantation without complications.
      Immunosuppression consisted of: corticosteroids, azathioprin and ciclosporin A.
      Ten weeks later he developed acute choroiditis with consecutive retinal
      detachment and neovascular glaucoma in one eye. In addition, 14 weeks after
      transplantation CT scans revealed multiple cerebral abscesses. RESULTS: In the
      course of the disease Nocardia farcinica (N. f.) was identified by cerebral
      stereotactic biopsy of a cerebral lesion, histological examination of the
      enucleated globe and sputum culture. Histologically filamentous, eosinophilic
      organisms were found. Microbiology identified aerobic actinomycetes in cultures
      and Nocardia farcinica by PCR. Therapeutically the combination of vancomycin,
      ampicillin, and sulbactam was successful. CONCLUSION: In immunosuppressed
      patients Nocardia farcinica can become life-threatening. One of the first
      manifestations may be a choroiditis. Infection of the respiratory tract followed
      by hematogenous spread is the common way of systemic nocardiosis. Biopsy followed
      by identification of species by PCR is recommended because of the specific
      therapeutic strategies associated with each species.

PMID- 11987048
TI  - Endoscopic resection of a distal femoral osteochondroma: description of the
      technique and case report.
AB  - This report describes the successful endoscopic treatment of an osteochondroma of
      the distal femur. We discuss the surgical technique and the case report of a
      distal femoral osteochondroma that was endoscopically resected without any
      complications. This technique allows performing a resection that involves minimum
      morbidity and a prompt functional recovery.

PMID- 11987052
TI  - Enveloping of periosteum on the hamstring tendon graft in anterior cruciate
      ligament reconstruction.
AB  - Tendon-bone incorporation of a tendon graft within the bone tunnel is a major
      concern when using tendon graft for ligament reconstruction. Periosteum consists
      of multipotent mesodermal cells to form all varieties of connective tissue,
      including osteogenic and chondrogenic tissues. From our histologic and
      biomechanical studies in animals, a superior healing process and stronger healing
      strength can be achieved when periosteum is sutured onto the tendon inserted
      within a bone tunnel. We applied this idea to anterior cruciate ligament
      reconstruction to enhance tendon-bone healing. A quadruple-stranded hamstring
      tendon graft is used. A piece of periosteum, 3 x 3 cm, harvested from the
      anterior cortex of proximal tibia, is split into 2 rectangle flaps (1.5 x 3 cm
      each). The periosteum flaps are wrapped and sutured around the tendon graft at
      the portions near the femoral and tibial tunnel openings. The cambium layer is
      faced outside to the bone tunnel. Periosteum is easy to harvest from proximal
      tibia, where is a routine incision for harvesting hamstring tendons. Besides the
      potential for enhancement of tendon-bone healing, periosteum may be able to seal
      off the intra-articular opening in a very early period to avoid synovial fluid
      reflux into the tunnel.

PMID- 11987053
TI  - How to become a better author without really trying.

PMID- 11987054
TI  - Arthroscopic subscapularis tendon repair: Technique and preliminary results.
AB  - PURPOSE: Our objective was to evaluate the preliminary results of 25 consecutive
      arthroscopic subscapularis tendon repairs. TYPE OF STUDY: Case series. METHODS:
      All 25 shoulders had longer than 3 months follow-up, with an average of 10.7
      months (range, 3 to 48 months). The average age was 60.7 years (range, 41 to 78
      years). The average time from onset of symptoms to surgery was 18.9 months
      (range, 1 to 72 months). The shoulders were evaluated using a modified UCLA
      score, Napoleon test, lift-off test, radiographs, and magnetic resonance imaging
      (MRI). Indications for surgery included clinical and/or MRI evidence of a rotator
      cuff tear. An arthroscopic suture anchor technique devised by the senior author
      (S.S.B.) was used for repair. RESULTS: UCLA scores increased from a preoperative
      average of 10.7 to a postoperative average of 30.5 (P <.0001). By UCLA criteria,
      excellent and good results were obtained in 92% of patients, with 1 fair and 1
      poor result. Forward flexion increased from an average 96.3 degrees
      preoperatively to an average 146.1 degrees postoperatively (P =.0016). Eight of 9
      patients with a positive Napoleon test had complete tears of the subscapularis.
      All 7 patients with a negative Napoleon test had a tear of the upper half only.
      The lift-off test could not be performed reliably due to pain or restricted
      motion in 19 of the 25 patients. Eight patients had isolated tears of the
      subscapularis. The remaining 17 patients had associated rotator cuff tears with
      an average total tear size of 5 x 8 cm. Ten patients had proximal migration of
      the humerus preoperatively. Eight of these 10 patients had durable reversal of
      proximal humeral migration following surgery. These 8 patients improved their
      overhead function from a preoperative "shoulder shrug" with attempted elevation
      of the arm to functional overhead use of the arm postoperatively. CONCLUSIONS:
      (1) The senior author has been able to consistently perform arthroscopic repair
      of torn subscapularis tendons, with good and excellent results, in 92% of
      patients. (2) The Napoleon test is useful in predicting not only the presence of
      a subscapularis tear, but also its general size. (3) Combined tears of the
      subscapularis, supraspinatus, and infraspinatus tendons are frequently associated
      with proximal humeral migration and loss of overhead function. Arthroscopic
      repair of these massive tears can produce durable reversal of proximal humeral
      migration and restoration of overhead function.

PMID- 11987055
TI  - Subacromial and intra-articular morphine versus bupivacaine after shoulder
      arthroscopy.
AB  - PURPOSE: Multiple studies have compared the effects of intra-articular
      bupivacaine and morphine for postoperative pain control after arthroscopy of the
      knee. To date, these agents have not been compared in the shoulder. The purpose
      of this study was to compare intra-articular (IA)/subacromial (SA) morphine,
      bupivacaine, and placebo after shoulder arthroscopy. TYPE OF STUDY: Prospective,
      double-blind, randomized clinical trial. METHODS: The effectiveness of each drug
      was measured by comparing the amount of supplemental analgesics required as well
      as the evaluation of each patient's level of pain after surgery. A visual analog
      scale was used to record each patient's level of pain before surgery and at
      various time intervals after surgery. The amount of supplemental analgesic was
      likewise recorded for 24 hours after surgery. Sixty-four patients were randomized
      into 3 groups and injected with morphine (n = 22), bupivacaine (n = 22), or
      saline (n = 20) at the conclusion of shoulder arthroscopy. The injection was
      directed intra-articular as well as subacromial if surgical dissection had been
      performed in this area. Statistical significance was determined at P <.05.
      RESULTS: There were no differences between groups before surgery. A statistically
      significant difference in pain level at 30 and 60 minutes was found. At 30 and 60
      minutes, patients who were administered IA/SA bupivacaine reported average pain
      levels less than those administered morphine or saline. Morphine was not
      statistically different from saline at reducing postarthroscopy pain at any time
      interval. Despite differences in pain level, there were no significant
      differences in the amount of supplemental analgesics requested at any time
      interval among these 3 groups. CONCLUSIONS: IA/SA morphine does not contribute to
      postoperative pain control after shoulder arthroscopy, whereas IA/SA bupivacaine
      improves pain control during the first 60 minutes after surgery.

PMID- 11987056
TI  - Arthroscopic revision Bankart repair: a prospective outcome study.
AB  - PURPOSE: The clinical outcome of the revision surgery for the failed Bankart
      repair is not well known. The purpose of this study was to prospectively analyze
      a series of patients with recurrent instability after primary Bankart repair that
      were revised arthroscopically using a suture-anchor technique. TYPE OF STUDY:
      Prospective, nonrandomized outcome study. METHODS: Twenty-three patients with
      failed Bankart repair were treated with arthroscopic surgery and were followed up
      for a mean of 36 months (range, 24-52 months; SD, 9 months). There were 21 men
      and 2 women with the mean age of 24 years (range, 17-34 years; SD, 4.4 years).
      Eight patients had previously received an open Bankart repair (5 transosseous
      suture technique, 3 suture-anchor technique), and 15 had received an arthroscopic
      repair (10 transglenoid multiple-suture technique, 5 suture-anchor technique).
      The revision surgery included repair of the anterior labrum using suture anchors
      and nonabsorbable sutures, capsular plication, and proximal shift of the inferior
      capsule with or without closure of the rotator interval. The characteristics of
      the patients, possible modes of failure, surgical findings, shoulder scores
      (University of California at Los Angeles [UCLA] scale, Simple Shoulder Test, and
      Rowe score), and clinical outcome were evaluated. RESULTS: Recurrent instability
      developed at a mean of 21 months (range, 11-39 months; SD, 8 months) after the
      initial stabilization. A possible cause of failure in 5 patients was a
      nonanatomic repair, with the labral tissue fixed proximal or medial to the
      glenoid margin. At the follow-up, 15 patients had excellent results, 4 good, 3
      fair, and 1 poor, according to the UCLA scale. The mean Rowe score improved from
      87.3 (range, 30-100; SD, 12.6) to 91.2 (range, 40-100; SD, 14.2) (P =.023). The
      Simple Shoulder Test responses improved from 8 yes responses preoperatively to 11
      postoperatively. Eighteen patients achieved an activity return of more than 90%
      of preinjury level. Five patients had recurrence after revision surgery (1 frank
      dislocation, 2 subluxation, 2 positive anterior apprehension sign). Engagement in
      contact sports was correlated with the recurrence (r =.683, P =.003). With the
      number available, no significant difference could be detected in the outcome
      between the types of the primary surgery. Arthroscopic revision Bankart repair
      did not result in any additional loss of external rotation compared with the
      contralateral side (P =.723). The most predictable factor for the functional
      return was preoperative range of external rotation (r =.793, P =.001).
      CONCLUSIONS: Arthroscopic revision Bankart surgery using suture anchors can
      provide a satisfactory outcome, including a low recurrence rate and reliable
      functional return, in carefully selected patients.

PMID- 11987057
TI  - The cosmetic appearance of the biceps muscle after long-head tenotomy versus
      tenodesis.
AB  - PURPOSE: This study evaluates the cosmetic appearance of the biceps muscle after
      arthroscopic, intra-articular biceps tenotomy versus tenodesis by presenting
      subjective outcome results in patients with refractive bicipital pain. TYPE OF
      STUDY: Retrospective study evaluating clinical follow-up of patients with
      refractive and chronic bicipital pain. METHODS: Five consecutive years of
      patients receiving biceps tenotomy (80 patients; 40 males, 40 females; average
      age, 58 years) or tenodesis (80 patients; 51 males, 29 females; average age, 54
      years) procedures were retrospectively followed-up by grading anterior shoulder
      pain, muscle spasms in the biceps, and cosmetic deformity of the biceps muscle.
      Statistics were done by chi(2) analysis. RESULTS: When assessing the follow-up
      questions, no statistical significance was found between the biceps tenotomy and
      biceps tenodesis groups. There was also no statistical significance when
      comparing the biceps tenotomy and biceps tenodesis groups when evaluating only
      the men, women, and men versus women with respect to the questions assessed.
      CONCLUSIONS: In the majority of patients in which a biceps tenotomy is performed,
      we note that the cosmetic appearance of the biceps muscle, the grade of muscle
      spasms of the biceps, and the level of anterior shoulder pain would present with
      little difference than if a tenodesis had been performed. Therefore, a biceps
      tenotomy may be a reasonable alternative to a biceps tenodesis in patients with
      refractive and chronic bicipital pain.

PMID- 11987058
TI  - Quantifying glenoid bone loss arthroscopically in shoulder instability.
AB  - PURPOSE: Our goal was to establish a consistent methodology for quantifying
      glenoid bone loss by arthroscopic means. TYPE OF STUDY: This study was an
      anatomic investigation of glenoid structure and its consistent anatomic landmarks
      as determined by arthroscopic means in live subjects and by direct measurement in
      fresh-frozen cadaver specimens. METHODS: We arthroscopically evaluated and
      measured the location of the bare spot of the glenoid in 56 subjects that had no
      evidence of instability (average age, 40 years). We also measured the exact
      location of the glenoid bare spot in 10 cadaver shoulders (average age, 76
      years). RESULTS: The bare spot of the glenoid was a consistent reference point
      from which to determine glenoid bone loss because it was located almost exactly
      at the center of the circle that was defined by the articular margin of the
      inferior glenoid below the level of the midglenoid notch. The tightly clustered
      standard deviations of the bare spot measurements in both the live subjects and
      the cadaver specimens confirmed its consistent location. CONCLUSIONS: The glenoid
      bare spot can be used as a central reference point to quantify the percentage
      bone loss of the inferior glenoid. Such objective measurement of glenoid bone
      loss can be clinically useful to the surgeon in deciding whether bone grafting is
      necessary to restore stability to the shoulder with a bone-deficient glenoid.

PMID- 11987059
TI  - Radiofrequency thermal effects on the human meniscus: an in vitro analysis.
AB  - PURPOSE: The purpose of this study was to evaluate the thermal effects produced
      in meniscal tissue with different radiofrequency (RF) energy levels and exposure
      times using a bipolar device. TYPE OF STUDY: An anatomic in vitro analysis of the
      thermal effects of an RF device. METHODS: A specially designed jig was used to
      apply RF energy under a constant force to cadaveric menisci. Three different
      energy levels were applied for 4 different contact times. RESULTS: The overall
      mean depth of thermal change was 547 microm (range, 468 to 650 microm). There
      were no significant differences or trends when contact time and energy were
      varied. CONCLUSIONS: These data suggest that increased contact times and energy
      outputs are not associated with increased thermal change in the meniscus. The
      submillimeter thermal denaturation was consistent with published reports using
      other thermal devices, such as laser.

PMID- 11987060
TI  - Effects of knee position, graft tension, and mode of fixation in posterior
      cruciate ligament reconstruction: a cadaveric knee study.
AB  - PURPOSE: Many knees exhibit residual ligament laxity after posterior cruciate
      ligament (PCL) reconstruction, which is believed to be technique related. The
      purpose of this study was to investigate the optimal graft tension, the best
      angle of knee flexion, and the mode of fixation in PCL reconstruction. TYPE OF
      STUDY: Anatomic biomechanical study. METHODS: A testing apparatus with
      frictionless bearing that allows other degrees of freedom except for flexion and
      extension of the knee joint was designed. The normal PCL tension at different
      angles of knee flexion was measured with a force transducer, and the optimal
      tension of the PCL graft that allows full range of knee motion was studied with a
      tensiometer in 12 cadaver knees. The modes of fixation failure between
      interference screw fixation and post fixation were studied with an Instron
      (Canton, MA) machine in 8 cadaver knees. RESULTS: The lowest PCL tension in
      normal knees was noted at 20 degrees to 30 degrees of knee flexion and the
      highest at 90 degrees. The optimal tension of PCL graft, which allows full range
      of knee motion, was 15 lb (68 N). The average load of graft failure was 417 (179
      730) N with interference screw fixation and 367 (149-701) N with post fixation
      when the patellar bone-tendon-bone graft was tested. There was no statistical
      difference in the failure load between interference screw fixation and post
      fixation (P =.753); however, the modes of failure differ. The sites of failure
      for interference screw fixation were 25% caused by rupture of ligament substance
      and 75% bone plug pullout; those of post fixation were 25% caused by rupture of
      ligament substance, 37.5% caused by fracture, and 37.5% as a result of suture
      breakage. CONCLUSIONS: The results of this study suggested that a 15-lb tension
      to the graft at 20 degrees to 30 degrees of knee flexion is optimal in PCL
      reconstruction. There was no statistical difference in the failure load between
      interference fixation and post fixation despite different modes of fixation
      failure.

PMID- 11987061
TI  - Anterior cruciate ligament injuries in the National Football League: epidemiology
      and current treatment trends among team physicians.
AB  - PURPOSE: To review the epidemiology of anterior cruciate ligament (ACL) injuries
      in the National Football League (NFL) and current treatment trends within this
      population. TYPE OF STUDY: Descriptive. METHODS: Part 1 of this study reviews the
      data collected in the NFL Injury Surveillance System from 1986 to 1995 with
      respect to these injuries. Included in this review are the specifics surrounding
      these injuries such as exposure type (game versus practice), position, mechanism,
      and playing surface on which the injury occurred. Part 2 of this analysis focuses
      on present treatment performed on these high-level athletes through a survey that
      was sent to and completed by all 31 NFL team orthopaedic surgeons. RESULTS: The
      total number of ACL injuries in this select population has remained constant over
      the period analyzed. CONCLUSIONS: Current preferred treatment technique favors
      endoscopic patellar tendon autograft reconstruction.

PMID- 11987062
TI  - Interference screw divergence in femoral tunnel fixation during endoscopic
      anterior cruciate ligament reconstruction using hamstring grafts.
AB  - PURPOSE: To compare the divergence angles between bioabsorbable interference
      screws inserted into the femoral tunnel with the screwdriver placed through the
      anteromedial portal to those inserted with the screwdriver placed through the
      tibial tunnel and to examine the effect of the femoral tunnel interference
      screws' divergence angles on fixation strength of hamstring grafts after anterior
      cruciate ligament (ACL) reconstruction using hamstring grafts. TYPE OF STUDY:
      Cadaveric biomechanical pullout study. METHODS: ACL reconstruction was performed
      in 8 pairs of fresh-frozen human cadaveric knees using hamstring grafts fixed
      within the femoral tunnels using bioabsorbable interference screws. Within
      matched pairs, 1 screw was placed into the femoral tunnel using a screwdriver
      placed through the tibial tunnel (group 1), and in the other knee it was placed
      into the femoral tunnel using a screwdriver placed through the anteromedial
      portal (group 2). Radiographs were taken to measure the degree of divergence
      between the interference screw and the femoral tunnel. After disarticulation,
      pullout strength was then measured using a cyclic-loading model. RESULTS: In
      group 2, there was significantly more divergence between the screw and the
      femoral tunnel compared with group 1, particularly in the sagittal plane (average
      14.4 degrees compared with 3.4 degrees, P =.00014). With the number of specimens
      available for comparison, no significant difference was detected between the 2
      groups with regard to 3 mm and 5 mm of pullout when cyclically loaded (P =.77
      and.74, respectively). CONCLUSIONS: The increased technical difficulty, combined
      with the potential risks of tibial tunnel widening and graft damage, with
      placement of the screwdriver through the tibial tunnel for the purpose of
      decreasing femoral interference screw divergence in ACL reconstruction using
      hamstring grafts may not be justified.

PMID- 11987063
TI  - Internal health status belief and lower perceived functional deficit are related
      among anterior cruciate ligament-deficient patients.
AB  - PURPOSE: Health locus of control has been shown to influence the recovery process
      after injury and surgery. This study attempted to determine relationships between
      patient perceptions of health locus of control and their perceived functional
      limitations after anterior cruciate ligament (ACL) rupture. An external health
      locus of control refers to the belief that one's outcome after injury or surgery
      is under the control of powerful others or is determined by fate, luck, or
      chance. An internal health locus of control refers to the belief that one's
      outcome is directly related to individual patient behaviors. TYPE OF STUDY: Quasi
      experimental, posttest only design. METHODS: Over a 1-year time period, 70
      consecutive patients with unilateral ACL deficiency (acute, <1 month after onset)
      agreed to participate in this study. All data were collected 1 week before ACL
      reconstruction. Subjects completed the Health Locus of Control Scale (HLC) and
      the physical function section of the Short Form 36 (SF-36) Health Survey. A
      Kruskal-Wallis 1-way analysis of variance was used to assess group differences (P
      <.05) based on SF-36 physical function score classification. RESULTS: Subjects
      with minimal perceived functional limitations (SF-36 physical function group 3)
      displayed lower (more internal) HLC scores (29.6 +/- 4.4; range, 24-36) than
      subjects with moderate perceived functional limitations (SF-36 physical function
      group 2) (33.0 +/- 6.1; range, 22-44) or subjects with maximal perceived
      functional limitations (SF-36 physical function group 1) (33.9 +/- 2.8; range, 30
      38). CONCLUSIONS: Subjects with lower perceived functional limitations regarded
      their health status as being controlled more by internal factors. It is not
      proven whether there is a cause-and-effect relationship or which of these
      parameters is the antecedent. Related reports suggest that perception of control
      may positively influence functional outcome and disability levels. Patients who
      perceive preoperative pain and functional limitation to be excessive may have low
      tolerance for the stressors associated with surgery and postoperative
      rehabilitation. With these patients, a more conservative surgical and
      rehabilitation approach may be better. Alternatively, methods to change their
      perceptions, such as cognitive therapy, may have a positive role.

PMID- 11987064
TI  - Rotator cuff tears: the effect of the reconstruction method on three-dimensional
      repair site area.
AB  - PURPOSE: To quantitatively determine the 3-dimensional (3-D) area of the original
      supraspinatus insertion and compare it with the repair-site area after 4
      reconstructions of a simulated supraspinatus tear. TYPE OF STUDY: Ex vivo
      biomechanical study. METHODS: The outline of the original supraspinatus insertion
      was obtained in 10 human cadaveric shoulders using a 3-D digitizer. A
      supraspinatus tear was created and 4 repair techniques were evaluated:
      transosseous simple suture (TOS), transosseous mattress suture (TOM), suture
      anchor simple suture (SAS), suture-anchor mattress suture (SAM). The 3-D outlines
      of the reconstructed supraspinatus insertion were digitized after each repair.
      The outlines of the original supraspinatus insertion and repair areas were
      superimposed onto humeral geometry obtained from a laser scanner, and surface
      areas were calculated. RESULTS: The original supraspinatus insertion area was
      larger than any of the repair-site areas (P <.05). On average, TOS provided a 20%
      larger repair-site area than the other repairs (P <.05). Repair-site areas were
      not different among TOM, SAS, or SAM repairs (P >.05) and covered 67% of the
      original supraspinatus insertion. CONCLUSIONS: None of the tested repairs
      restored the area of the original supraspinatus insertion. The larger repair-site
      area of the TOS repair suggests that this technique provides better potential for
      healing and, ultimately, greater strength of repair.

PMID- 11987065
TI  - Surgical and nonsurgical management of rotator cuff tears.
AB  - Although rotator cuff tears may be asymptomatic, symptomatic tears have had
      treatment varying from nonoperative therapy and debridement with subacromial
      decompression to operative repair. The benchmark for comparison should be
      nonoperative treatment when deciding to proceed to operative repair. This review
      will analyze the recent peer-reviewed publications describing results of
      operative repair, how this regimen differs with nonoperative treatment, and any
      outcome differences between operative and nonoperative treatment. Operative
      repair has consistently shown a higher rate of pain relief in patients (85%) and
      a better return of strength. Nonoperative treatment is expected to produce
      satisfactory relief of pain in only 50% of patients and no improvement in
      strength at long-term follow-up.

PMID- 11987066
TI  - Arthroscopic treatment of a transarticular low-velocity gunshot wound using
      tractoscopy.
AB  - An unusual case of a close-range, low-velocity gunshot wound to the knee is
      presented. Arthroscopic debridement was accomplished using standard anterior
      portals as well as the existing entry and exit wounds. All bullet fragments were
      successfully removed from the joint by arthroscopy and tractoscopy. A minimally
      displaced marginal, lateral tibial plateau fracture was observed and treated with
      restricted weight bearing and active motion. The patient recovered uneventfully
      and maintained full knee range of motion and a normal gait.

PMID- 11987067
TI  - Subchondral microfracture of the knee without osteonecrosis after arthroscopic
      medial meniscectomy.
AB  - We report a case of an osteonecrosis-like lesion of the knee that developed
      shortly after an arthroscopic medial meniscectomy. Clinical presentation,
      physical findings, and imaging of the knee including magnetic resonance imaging
      were similar to those of the cases that have been reported as osteonecrosis after
      meniscectomy. However, histologic analysis of the lesion revealed that there was
      no osteonecrosis but rather a subchondral microfracture with active callus
      formation.

PMID- 11987069
TI  - Patient positioning for shoulder arthroscopy based on variability in lateral
      acromion morphology.
AB  - The purpose of this article is to highlight the variability among shoulders in
      the relationship between the lateral acromion and the humeral head and to
      describe how this variability may influence a surgeon's choice of patient
      positioning for shoulder arthroscopy. In cases of increased lateral coverage of
      the humeral head by the acromion, arthroscopic access to the superior aspect of
      the glenoid through lateral portals becomes increasingly difficult because of a
      narrowed corridor of approach. Placing the ipsilateral arm in traction will lower
      the station of the humeral head and widen the arthroscopic corridor of approach
      to the superior labrum. Based on preoperative assessment of lateral acromion
      morphology, if the surgeon determines that inferior displacement of the humeral
      head of 25% or more of the humeral head diameter will be necessary to achieve
      adequate arthroscopic accessibility of the superior glenoid through lateral
      portals, we recommend the lateral decubitus position with continuous traction on
      the ipsilateral arm over the beach-chair position.

PMID- 11987068
TI  - Preoperative magnetic resonance imaging diagnosis of the floating anterior
      inferior glenohumeral ligament.
AB  - Approximately a century ago, labral avulsion from the glenoid was described as a
      source of recurrent anterior shoulder dislocation. Since then, the significance
      of other origins of shoulder instability has been a controversial issue.
      Cadaveric dissection, biomechanical evaluation, and surgical observation have led
      to the discovery of additional pathologic conditions associated with glenohumeral
      instability that must be properly identified and addressed for operative success.
      Recently, several authors have emphasized the importance of lesions of the
      glenohumeral ligament as a cause of post-traumatic shoulder instability. One such
      condition is bipolar avulsion of the anterior inferior glenohumeral ligament
      (AIGHL), or floating AIGHL. In previous reports, this finding has only been
      identified during surgery. We present a case of traumatic anterior shoulder
      dislocation in which a preoperative diagnosis of floating AIGHL was made by
      magnetic resonance imaging. Recognition of this rare lesion before surgical
      intervention is advantageous for appropriate preoperative planning and management
      of patients with posttraumatic anterior glenohumeral instability.

PMID- 11987070
TI  - Double-bundle anatomic anterior cruciate ligament reconstruction using bone
      hamstring-bone composite graft.
AB  - The bone-hamstring-bone (BHB) composite graft is a hybrid ligament reconstruction
      methodology that combines the advantages but eliminates the disadvantages of the
      bone-patellar tendon-bone (BPTB) and tendon of semitendinosus and gracilis muscle
      (STG) methods. We have developed an innovative modified BHB method involving
      anatomic anterior cruciate ligament (ACL) reconstruction. It takes into account
      the 2 bundles of the ACL: the anteromedial bundle and the posterolateral bundle.
      The composite graft was prepared by folding the gracilis and the semitendinosus
      tendons twice and flanking the ends by bone blocks obtained from the tibia. One
      tunnel of 11-mm diameter was made in the tibia and the femur, and the top of the
      graft was introduced into the femoral socket; the distal end of the graft was
      rotated 90 degrees in the counterclockwise direction for a right knee and 90
      degrees in the clockwise direction for a left knee to apply a twist to the graft,
      giving rise to an anteromedial bundle and a posterolateral bundle. The bone
      blocks attached to the graft were fixed with 2 interference screws. Modified BHB
      technique allows free selection of the location of the bone plug, minimizes the
      intra-articular length of the graft, and maintains the double-bundle structure of
      the original ACL.

PMID- 11987071
TI  - Repair of quadriceps tendon ruptures using suture anchors.
AB  - The repair of ruptured quadriceps tendon is commonly performed by weaving sutures
      through the ruptured tendon and then attaching the tendon to the bone by passing
      these sutures through tunnels in the superior patella. This technical note is the
      first report we are aware of in the English language literature of a technique
      that uses suture anchors to attach the tendon to bone.

PMID- 11987072
TI  - Re: Coplaning of the acromioclavicular joint.

PMID- 11987074
TI  - Re: Expression of cytokines after meniscal rasping to promote meniscal healing.

PMID- 11987076
TI  - Tibial hole placement in ACL grafts.

PMID- 11987078
TI  - Ten years of experience with third and fourth branchial remnants.
AB  - BACKGROUND: Third and fourth branchial remnants may result in cysts and abscesses
      that are in close contact with the thyroid gland. These anomalies are rare and
      often present diagnostic and therapeutic challenges. METHODS: The charts of
      patients diagnosed with a branchial anomaly between July 1991 and July 2001 at
      the Montreal Children's Hospital were reviewed. All cases of third and fourth
      branchial remnants or pyriform sinus fistulae were identified. Clinical
      presentation, imaging, treatment, and outcome were recorded. RESULTS: Eight
      patients with a third or fourth branchial anomaly were identified and ranged in
      age from birth to 13 years. All anomalies were left sided. Presenting symptoms
      consisted of an asymptomatic cervical mass (n = 1), an infected mass (n = 5),
      neonatal respiratory distress (n = 1), and 1 incidental cyst found on magnetic
      resonance imaging. Ultrasonography was useful in suggesting the diagnosis in 7
      cases. Barium swallow was performed in 3 patients with 2 positive results.
      Pharyngoscopy results showed the internal opening in 2 of 7 patients. A portion
      of the thyroid gland was resected in 6 patients. One patient has not yet
      undergone a definitive procedure. There was 1 recurrence in a patient whose
      pathology did not confirm a branchial remnant. CONCLUSIONS: The diagnosis and
      management of pyriform sinus anomalies are challenging. Ultrasound scan, computed
      tomography scan, barium swallow, and pharyngoscopy are all useful. The portion of
      thyroid involved in the fistula must be excised en bloc with the inflammatory
      mass, and the tract should be ligated at the level of the pharynx to minimize
      recurrence.

PMID- 11987079
TI  - Intraoperative ultrasound reduces ECMO catheter malposition requiring surgical
      correction.
AB  - BACKGROUND/PURPOSE: One hundred ninety-three cannulation procedures for
      extracorporeal membrane oxygenation (ECMO) have been performed at the authors'
      institution from 1994 to now. Before 1996, their practice had been to position
      these catheters exclusively by clinical assessment and chest radiograph. Since
      then, the authors have utilized intraoperative ultrasound guidance during
      cannulation procedures to confirm proper tip position. This retrospective
      analysis was undertaken to establish whether this practice has reduced the rate
      of surgical repositioning of ECMO catheters in these patients. METHODS: A
      retrospective chart review was performed for all infants who underwent ECMO
      cannulation procedures at the authors' institution. Numbers of infants requiring
      surgery to readjust ECMO catheter position were totaled. Cases were categorized
      according to the presence or absence of intraoperative ultrasound scan.
      Statistical significance was determined using X(2) analysis, Student's t test, or
      analysis of variance where appropriate. RESULTS: There were 193 ECMO cannulations
      performed. Of the 101 procedures done without ultrasound scan, 18 necessitated
      surgical repositioning. In contrast, only 3 of the 92 catheters placed with
      ultrasound assistance required reoperation. This represents a reduction the rate
      of repositioning from 17.8% to 3.3% of cannulations (P =.003). CONCLUSIONS: Based
      on these findings, the authors advocate the use of intraoperative ultrasound
      imaging to optimize the position of ECMO catheters. This high rate of initial
      success helps avoid the potential morbidity of ECMO circuit malfunction, repeat
      neck dissection, and catheter manipulation in these critically ill,
      anticoagulated patients.

PMID- 11987080
TI  - Laparoscopic appendectomy in children: A favorable alternative in simple and
      complicated appendicitis.
AB  - BACKGROUND/PURPOSE: The laparoscopic treatment of pediatric appendicitis remains
      controversial, particularly in complicated cases (gangrene and perforation). This
      study evaluates outcomes of open (OA) and laparoscopic appendectomy (LA).
      METHODS: The 391 cases of pediatric appendectomy performed between January 1998
      and January 2001 were reviewed for age, sex, weight, type and length of
      intervention, operative description, antimicrobial therapy, analgesia,
      complications, length of hospitalization, and histopathology. RESULTS: A total of
      126 patients were operated on by laparoscopy, 262 by laparotomy, and there were 3
      conversions (LA + OA). LA patients were older (11.9 v 9.6 years; P <.001) and
      more frequently girls (57.1% v 38.2%; P =.0004). LA took longer to perform (45.7
      v 40.6 minutes; P =.0014). Operatively, 24.6% of LAs were described as
      complicated compared with 22.5% in OA. Narcotic use was equivalent in both groups
      (1.16 v 1.29 days; P =.434), as was the incidence of complications, either
      operative (1.6% v 0.4%; P =.20) or postoperative (10.3% v 8.02%; P =.32).
      Hospitalization was shorter in LA (2.38 v 2.94 days; P =.0131). Histopathology
      was negative in 21.4% of LAs compared with 13% of OAs (P =.032). CONCLUSIONS:
      Laparoscopic appendectomy does not increase the incidence of complications, even
      with gangrenous or perforated appendicitis. The length of intervention is
      prolonged by 5 minutes on average. This technique allows for a shorter
      hospitalization.

PMID- 11987081
TI  - Probiotic supplementation reduces the risk of bacterial translocation in
      experimental short bowel syndrome.
AB  - BACKGROUND/PURPOSE: Probiotics are live organisms that survive passage through
      the gastrointestinal tract and have beneficial effects on the host. Lactobacillus
      and Bifidobacterium have been recommended for cholesterol lowering, acute
      diarrhea, prevention of cancer, or inflammatory bowel disease. On the other hand,
      after massive bowel resection, bacterial overgrowth is frequent and favors
      bacterial translocation (BT). The possible beneficial effects of Bifidobacterium
      lactis (BL) administration on BT in experimental short bowel syndrome (SBS), have
      not been investigated. The aim of this study was to test the hypothesis that BL
      administration decreases BT in SBS in animals fed orally. METHODS: One hundred
      twenty-eight adult Wistar rats fed orally with standard rat chow and tap water
      "ad libitum" were maintained in individual metabolic cages for 10 days and
      divided into 3 groups: control group (n = 71): nonmanipulated animals; RES group
      (n = 39): 80% gut resection from 10 cm beyond the angle of Treitz to 10 cm above
      the cecum; RES-PRO group (n = 18): same resection and daily 7.8 x 10(8) CFU B
      Lactis administration, after orogastric intubation. At the end of the experiment
      they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal
      blood specimens were recovered and cultured. Bacterial identification in blood
      was made by conventional methods, and MLN culture was considered positive with a
      growth over 100 CFU/g. RESULTS: Bacterial translocation was detected in 6% of
      control group rats. The incidence of BT in the RES group was 87% (34 of 39),
      whereas only 50% (9 of 18) of RES-PRO animals had BT (P <.05). The relative risk
      reduction (RRR) was 0.43 (95% Cl 0.14 to 0.72), and the number needed to treat
      (NNT) was 3 (95% Cl 2 to 8). In other words, animals that received BL had the
      risk of BT reduced by 43% (RRR of 0.43), and of every 3 animals treated, 1 is
      expected to be free of BT (NNT of 3). CONCLUSION: Administration of B Lactis
      reduces the incidence of BT in adult Wistar rats after 80% gut resection.

PMID- 11987082
TI  - The impact of changing neonatal respiratory management on extracorporeal membrane
      oxygenation utilization.
AB  - BACKGROUND: The introduction of inhaled nitric oxide (INO) and high-frequency
      oscillatory ventilation (HFV) has had a profound effect on the use of
      extracorporeal membrane oxygenation (ECMO) for respiratory failure in neonates
      without congenital diaphragmatic hernia (CDH). The purpose of this study was to
      evaluate the changes in the demographics and outcome of non-CDH neonates who
      underwent ECMO for hypoxemic respiratory failure. METHODS: All neonates (non-CDH
      and noncardiac) who underwent ECMO between January 1, 1989 and January 1, 2001
      were reviewed. Patients were separated into 3, 4-year periods for comparison
      (period A, 1989 through 1992; B, 1993 through 1996; C, 1997 through 2000). Data
      were examined by analysis of variance and contingency table analysis. RESULTS:
      There was a progressive decline in the total number of neonates requiring ECMO
      over time (period A, 172; B, 114; C, 56; P <.01). The utilization of pre-ECMO
      alternate respiratory therapies such as INO (period A, 0%; B, 23%; C, 98%; P
      <.01) and HFV (period A, 9%; B, 61%; C, 89%; P <.01) have increased significantly
      associated with an increase in the age of ECMO initiation (Period A, 40.5 hours;
      B, 58.3 hours; C, 68.5 hours; P <.01). The length of ECMO run also has increased
      (period A, 154.7 hours; B, 193.0 hours; C, 174.5 hours; P <.01), but the overall
      mortality rate has remained unchanged. CONCLUSIONS: With the increasing use of
      INO and HFO, the absolute number of non-CDH, noncardiac neonates with hypoxemic
      respiratory failure requiring ECMO has decreased. Initiation of ECMO has become
      progressively later likely because of the use of these rescue therapies, but the
      overall mortality rate remains unchanged despite this delay.

PMID- 11987083
TI  - Is laparoscopic subtotal colectomy better than open subtotal colectomy in
      children?
AB  - PURPOSE: The role of laparoscopic colectomy is not defined clearly. The aim of
      this study was to compare clinical outcomes of laparoscopic versus open subtotal
      colectomy in children with inflammatory bowel disease. METHODS: Eight consecutive
      patients undergoing laparoscopic subtotal colectomy were compared with 10
      consecutive patients undergoing open subtotal colectomy. All patients were
      refractory to medical management on immunosuppressive regimens. Operating time,
      length of postoperative stay and intravenous narcotic use, time to return of
      intestinal function, and perioperative complications were compared between the
      groups. RESULTS: Operating times were significantly longer in the laparoscopic
      group (mean laparoscopic, 4 hours 40 minutes v mean open 2 hours 25 minutes; P
      <.01). There was no difference between the 2 groups in length of postoperative
      intravenous narcotics or hospital stay. Ileostomy output occurred earlier (mean
      laparoscopic, 2.5 days v mean open 3.8 days; P =.01), and there was a trend
      toward earlier oral intake in the laparoscopic group. A total of 6 complications
      occurred in 4 patients in the laparoscopic group compared with 5 complications in
      5 patients in the open group. CONCLUSIONS: Perioperative clinical outcomes,
      including complication rates, are similar with laparoscopic and open subtotal
      colectomy. Laparoscopic subtotal colectomy can be performed safely in children
      with improved cosmesis.

PMID- 11987085
TI  - Glucocorticoid receptor gene expression in the hypoplastic lung of newborns with
      congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: In experimentally produced congenital diaphragmatic hernia
      (CDH), antenatal glucocorticoids have been shown to improve morphologic and
      biochemical lung immaturity and normalize the thickened pulmonary vascular wall.
      The action of glucocorticoids on a target tissue is mediated by glucocorticoid
      receptors (GRs), which have 2 isoforms; GRalpha binds glucocorticoids and acts as
      a ligand-dependent transcription factor, and GRbeta does not bind glucocorticoids
      and acts as an inhibitor of GRalpha. The aim of this study was to examine the
      expression of GR gene and its isoforms in the CDH lung. METHODS: RNA was
      extracted from archival lung tissue of 11 patients (mean age, 3.5 days) with CDH.
      Five age-matched newborns (mean age, 13.5 days) with sudden death syndrome served
      as control. Reverse transcription (RT) and polymerase chain reaction (PCR) was
      performed using primers specific to the common region of GR, GRalpha, and GRbeta.
      Soluble enzyme immunohistochemistry was carried out using polyclonal antibodies
      to GRalpha. RESULTS: Relative mRNA levels of GR, GRalpha, and GRbeta as detected
      by RT-PCR were increased significantly in CDH lung compared with controls.
      GRalpha immunoreactivity confined only to the cytoplasm of the cells was markedly
      increased in the epithelium and interstitial cells in the CDH lung compared with
      controls. CONCLUSION: The findings of increased mRNA expression of GR and
      particularly of its isoform GRalpha in the CDH lung suggests that GR may play an
      important role in regulating target cell responsiveness to glucocorticoids in the
      hypoplastic lung.

PMID- 11987084
TI  - Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis.
AB  - BACKGROUND/PURPOSE: C-Kit-positive interstitial cells of Cajal (ICCs) have a key
      role in the normal motility function and development of the bowel. They are
      pacemaker cells, which facilitate active propagation of electrical events and
      neurotransmission in the bowel wall. ICCs are present in the bowel as myenteric
      ICCs (ICC(my)S) and muscular ICCs (ICC(mus)S). The aim of this study was to
      examine the distribution of c-Kit-positive ICCs and their relationship to the
      autonomic intrinsic innervation in bowel specimens from patients with isolated
      hypoganglionosis. METHODS: Full-thickness large bowel specimens were obtained
      from 6 patients with hypoganglionosis and from 4 patients during bladder
      augmentation (controls). Frozen sections and whole-mount preparations were
      stained using c-Kit immunohistochemistry, nicotinamide adenine dinucleotide
      phosphate (NADPH)-diaphorase, and acetylcholinesterase (AChE) histochemistry and
      evaluated using normal brightfield and confocal laser scanning microscopy.
      RESULTS: NADPH-diaphorase and AChE histochemistry findings showed characteristic
      histologic features of hypoganglionosis, eg, sparse and small myenteric ganglia
      and low or absent AChE activity in the lamina propria. Myenteric plexus in the
      normal bowel was surrounded by a dense network of c-Kit-positive ICC(my)S,
      whereas in hypoganglionosis sparse isolated ICC(my)S were found. C-Kit-positive
      ICC(mus)S were reduced markedly in the longitudinal and circular muscle layer and
      at the innermost part of the circular muscle in hypoganglionosis. CONCLUSION:
      Deficient expression of c-Kit-positive myenteric and muscular ICCs in the
      hypoganglionic colon may contribute to the motility dysfunction in the affected
      bowel.

PMID- 11987086
TI  - Midgut atresias result from abnormal development of the notochord in an
      Adriamycin rat model.
AB  - BACKGROUND/PURPOSE: Prenatal exposure to Adriamycin in a rat model (ARM) has been
      reported to lead to a spectrum of tracheoesophageal and associated malformations
      of the gastrointestinal tract, including multiple intestinal atresias. An
      abnormal relationship of the notochord with the foregut has been implicated in
      the formation of esophageal atresias. The authors hypothesised that midgut
      atresias arise from abnormal notochord development in the region of the midgut.
      This study was designed to examine the gut-notochord relationship during early
      embryonic development. METHODS: Timed pregnant Wistar rats were given 1.75 mg/kg
      of Adriamycin intraperitoneally on days 7, 8, and 9 of gestation. Embryos were
      recovered at 12-hour intervals from days 9.5 to 14, and at term. A control group
      was given saline instead of Adriamycin. Embryos were embedded in resin or wax,
      sectioned, and studied using light microscopy, paying particular attention to the
      notochord and surrounding structures. RESULTS: The notochord appeared identical
      in controls and experimental embryos on day 9.5. However, on day 10.5 the
      notochord was diffusely abnormal in ARM, distorted, and tethered to foregut as
      well as midgut compared with controls. This abnormality was not seen in control
      embryos. On day 12 the notochord abnormalities were more exaggerated in the
      region of the midgut in ARM embryos. Full-term ARM animals had esophageal and
      multiple intestinal atresias. CONCLUSIONS: The notochord is abnormal in the
      region of the developing midgut, and this may account for the occurrence of
      atresias found in this region.

PMID- 11987087
TI  - Differential effects of neonatal endotoxemia on heart and kidney carnitine
      palmitoyl transferase I.
AB  - BACKGROUND/PURPOSE: The heart and kidney are both affected in sepsis-related
      multiple organ failure. Both utilize fatty acid substrates during the neonatal
      period, and impairment of oxidative metabolism during sepsis could lead to
      bioenergetic failure. The enzyme carnitine palmitoyl transferase I (CPT I) is
      important in the control of fat oxidation in the neonatal period. The aim of this
      study was to determine the effects of sepsis on neonatal cardiac and renal CPT I.
      METHODS: Suckling rats received 300 microgram/kg lipopolysaccharide
      intraperitoneally. Mitochondria were isolated from the heart and kidney after 2
      hours. CPT I and II activity were measured radiochemically. Protein levels of M-
      and L- isoforms of CPT I, both of which are present in heart, were determined by
      Western blotting. RESULTS: CPT I activity was decreased significantly in the
      heart but not in the kidney by endotoxemia, whereas CPT II activity was the same
      in each organ. To investigate the mechanism of this decrease, we carried out
      Western blotting of the CPT I isoforms in heart mitochondria. Neither M- nor L-
      isoform was decreased in amount. To determine whether free-radical attack could
      directly inhibit CPT I activity, control heart mitochondria were incubated with
      free-radical generating systems. Although hydrogen peroxide had no effect on CPT
      I activity, the reactive oxygen species nitric oxide, superoxide, and
      peroxynitrite, all of which are generated in the heart during sepsis,
      significantly inhibited CPT I activity. CONCLUSIONS: The activity of CPT I, a
      rate-controlling step of fat oxidation, is significantly impaired in heart but
      not in kidney during neonatal sepsis. This may be caused by direct attack by free
      radicals, suggesting that antioxidant strategies could be of use in preventing
      sepsis-related cardiac damage.

PMID- 11987088
TI  - Laparoscopic surgery for pediatric varicoceles: Randomized controlled trial.
AB  - BACKGROUND/PURPOSE: The purpose of this investigation was to evaluate the
      advantages and the shortcomings of laparoscopic varicocelectomy compared with
      open traditional treatment of varicoceles. METHODS: A total of 654 patients were
      operated on for left-sided varicoceles over 5 years from 1995 to 2000. To
      evaluate the clinical efficiency of the treatment, the patients were divided
      randomly into 2 groups. Laparoscopic varicocelectomy (LV) was performed on 434
      patients, and open varicocelectomy (OV) in 220 patients. Outcome data looked at
      relapse rate, presence of hydrocele, wound complications, and testicular or
      scrotal edema. Operating time, postoperative length of stay, and pain control
      also were compared. In both groups, the operations were performed by Palomo's
      technique with preservation of lymphatics and mass ligation of the artery and
      veins in the retroperitoneum above the internal inguinal ring. RESULTS: In LV
      versus OV, relapse rates were 1.84% versus 1.36 (P < 0.5), hydrocele occurrence
      was 0.23% versus 1.82% (P < 0.1), wound complication was 0.23% versus 7.73%, and
      testicular or scrotal edema was 3.9% versus 13.1%. LV hospital stay was an
      average of 3 days versus 7 days for OV. Operating time was 15 minutes for LV
      versus 26 minutes in open. Postoperative analgesic use was almost cut in half
      with LV. CONCLUSION: The clinical efficacy of LV is superior to traditional OV.

PMID- 11987089
TI  - Effect of prenatal glucocorticoids and postnatal nitric oxide inhalation on
      survival of newborn rats with nitrofen-induced congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Pulmonary hypertension and pulmonary hypoplasia account for
      the high mortality rate associated with congenital diaphragmatic hernia (CDH). In
      animal models of CDH, postnatal nitric oxide (NO) inhalation resulted in
      significantly better survival rates and antenatal glucocorticoid administration
      in improved lung compliance. The objective of this study was to evaluate the
      combined effect of prenatal glucocorticoid administration and postnatal NO
      inhalation on the survival rate of newborn rats with nitrofen-induced CDH.
      METHODS: Right-sided CDH was induced by maternal administration of a single oral
      dose (100 mg, intraperitoneally) of nitrofen on day 11.5 of pregnancy.
      Dexamethasone (DEX, 0.25 mg/kg) was given in groups III and IV by maternal
      intraperitoneal injection on day 18.5 and 19.5 of pregnancy. Control animals
      (groups I and II) received vehicle alone. After spontaneous delivery, the newborn
      animals were exposed to either NO (80 ppm; groups II and IV) or room air (groups
      I and III). Vitality (Rat-Score), sO(2) and survival were monitored continuously
      for 12 hours until animals were killed. Hernia size was estimated as percentage
      of total thoracic content. RESULTS: Right-sided CDH was observed in 392 of 491
      newborn rats (81%). Animals with large hernias (>50%) died within 4 hours after
      birth, irrespective of treatment. Hernias with less than 50% of the thoracic
      volume were considered clinically relevant hernias. In this category, 12.5% of
      animals without treatment (group I) survived compared with 63.6% after NO
      treatment alone (group II; P <.01). Survival rate after DEX treatment alone
      (group III) was 69.4% (group III v I; P <.01). In group IV (DEX and NO) 95.2% of
      the animals survived (group IV v I; P <.001). In contrast to DEX alone, NO
      administration resulted in significantly better sO(2)(group II and IV) compared
      with group I (P <.05). CONCLUSION: Combination of prenatal maternal
      glucocorticoids and postnatal NO inhalation significantly improved survival rate
      of newborn rats with nitrofen-induced CDH.

PMID- 11987090
TI  - Experimental small bowel obstruction in chick embryos: Effects on the developing
      enteric nervous system.
AB  - BACKGROUND/PURPOSE: After surgical repair of congenital small bowel atresias,
      intestinal motility disorders often are observed. These may be caused by changes
      in the enteric nervous system (ENS) secondary to obstruction. To assess these
      changes, small bowel atresias were induced experimentally in chick embryos.
      METHODS: On day 11, the small intestines of 90 chicken embryos were ligated
      microsurgically in ovo. Breeding of the eggs was continued until day 19. The
      small bowel was removed, fixed, and embedded for silver-staining, semithin serial
      sections, and transmission electron microscopy. Additionally, acetyl
      cholinesterase (AChE)-staining was performed. Normal chick embryos of the same
      age served as controls. RESULTS: Macroscopically, experimentally induced small
      bowel atresias had the same characteristics as human newborns. Microscopically,
      the wall structure was preserved; however, the ENS differed markedly from
      controls. Both proximal and distal to the obstruction, the submucosal plexus was
      almost completely absent, whereas the myententeric plexus was diminished only in
      the proximal dilated blind pouch. The axonal net was disrupted additionally.
      Ganglion cells of the myenteric plexus in the proximal segment were arranged in
      longitudinal clusters of densely packed cells. In the distal segment ganglion
      cells formed round clusters. The cells of Cajal, which normally surround the
      myenteric ganglia, were absent in the proximal and distal segments. CONCLUSIONS:
      In our experiments, structural changes in the ENS could be observed secondary to
      experimentally induced small bowel atresias in the chick. Because of the lack of
      ischemia in this model, the main cause of these ENS changes seems to be the
      dilatation oft the proximal gut. Dilatations are common features in intestinal
      atresias, anorectal malformations, and Hirschsprung's disease. Our observations,
      thus, explain motility disorders after the surgical repair of these diseases.

PMID- 11987091
TI  - Monocyte and neutrophil activity after minor surgical stress.
AB  - BACKGROUND/PURPOSE: Surgical stress produces changes in the immune status of
      patients. In adults, major surgery causes immunosuppression, whereas minor
      operations stimulate immune responses. In children, the immunologic response to
      surgery has not been elucidated completely. The authors investigated the effects
      of minor surgery on immune response by analyzing neutrophil and monocyte
      phagocytosis and oxidative burst activity. METHODS: Sixteen children undergoing
      elective minor surgery were enrolled. Blood samples were collected before the
      operation (at time of induction of anesthesia), at the end of operation, and 72
      hours after surgery. Neutrophil and monocyte phagocytosis and oxidative burst
      activity were studied using a flow cytometric method. RESULTS: Phagocytosis and
      oxidative burst increased significantly at the end of the operation, both in
      neutrophils (7.4% and 14.3%, respectively) and monocytes (11.6% and 27%,
      respectively). The increase was only significant for monocytes (17.5%) 72 hours
      after surgery. White cell count did not show any significant changes. There was
      no significant correlation between phagocytosis, oxidative burst activity, and
      white cell count or neutrophil and monocyte count. CONCLUSIONS: This study shows
      that minor surgery in children induces immune activation by increasing neutrophil
      and monocyte phagocytosis and oxidative burst activity. Further studies are
      required to understand the molecular basis of these findings.

PMID- 11987092
TI  - Variability of inguinal hernia surgical technique: A survey of North American
      pediatric surgeons.
AB  - BACKGROUND/PURPOSE: The tradition of learning from mentors is a unique aspect of
      surgical training. With this in mind, the authors sought to document our roots by
      analyzing the technical variability of how pediatric surgeons perform their most
      frequent operation, the inguinal hernia, and compare these data with the original
      description by Drs William Ladd and Robert Gross. METHODS: A survey compiling the
      operative steps of an inguinal hernia repair as well as several key clinical
      situations involving hernias was mailed to pediatric surgeons in North America.
      These results then were compared with the original inguinal hernia technique by
      Drs Ladd and Gross. Results are recorded as the percent who concurred with their
      original description. RESULTS: A total of 447 of 640 (70%) surveys were returned.
      Geneologic data show that 81% of surgeons' hernia lineage could be traced to Drs
      Ladd and Gross. When compared with all respondents, Drs Ladd and Gross' hernia
      repair steps included incising Scarpa's fascia (61%), defining the external ring
      by pushing down with retractors (34%), incising the external oblique with
      scissors (18%), identifying the ileoinguinal nerve (81%), cleaning one underside
      of the external oblique (22%), bluntly spreading the cremasteric fibers (90%),
      elevating the sac with sharp dissection of the vessels (53%), opening the sac and
      inserting the forefinger into it (0%), bluntly dissecting the sac with forefinger
      and gauze (0%), ligating the sac with single ligature (22%) without twisting it
      (34%), leaving the distal sac untouched other than to drain fluid (78%), not
      inspecting the testicle (79%), performing a formal floor repair bringing external
      and internal oblique down to Poupart's ligament (10%), tightening the internal
      ring in both boys and girls (19% and 41%), using no local anesthetic (14%),
      closing Scarpa's fascia (94%), closing the skin with interrupted subcuticular
      sutures (49%), covering the incision with Collodion (48%), using the Stiles'
      dressing (0%), and only exploring the contralateral side if a hernia is suggested
      by history or physical examination (87% for boys, 60% for girls). The various
      other options surgeons use for their technique and their management decisions
      also are described. CONCLUSIONS: There is significant variability in the way
      pediatric surgeons perform inguinal herniorraphy. The differences from Drs Ladd
      and Gross' original description likely result from evolving techniques,
      experiences, and analysis of outcomes.

PMID- 11987093
TI  - Telehealth provides effective pediatric surgery care to remote locations.
AB  - PURPOSE: The aim of this study was to document the experience and patient
      satisfaction with providing pediatric surgery consultations and follow-up
      appointments to remote locations via audiovisual telecommunications technology.
      METHODS: From January 2000 to April 2001, 16 consecutive pediatric general
      surgery clinics were reviewed for the type of patient (new or review), the
      diagnosis, the adequacy and accuracy of the evaluation, and the ability to
      formulate a plan. In the first year, first-time users were requested to complete
      a satisfaction survey of 15 questions. Responses to 13 questions were recorded on
      a 4-point Likert scale, and 2 questions required a "yes" or "no" response.
      RESULTS: One hundred eighteen appointments were scheduled. Twenty patients did
      not show up or cancelled. There were 45 new patient consultations. Thirty-three
      patients were scheduled for surgery, of which, 21 are completed, and 12 are
      pending. There were no errors in diagnosis or changes in planned procedures.
      There were 42 patients seen in 53 follow-up sessions. Thirty-six surveys of a
      possible 53 were available for analysis. The mean rating of overall treatment
      experience at Telehealth was 3.47 (95% confidence interval 0.17). One hundred
      percent responded they would use Telehealth again and would recommend it to
      another person. CONCLUSION: Telehealth is an effective and acceptable way to
      provide pediatric general surgery clinics to remote locations.

PMID- 11987094
TI  - Evaluation of scooter-related injuries in children.
AB  - BACKGROUND/PURPOSE: The sudden popularity of the "scooter phenomenon" was
      followed by an increased rate of injuries associated with its use. This study
      evaluates the circumstances, types, degrees, and mechanisms of injury related to
      the use of a scooter in the pediatric population. METHODS: From January 2000 to
      February 2001, the emergency files of all the children arriving at the authors'
      institutions with a diagnosis of "scooter related trauma" were reviewed. RESULTS:
      One hundred fifty-six cases were recorded; 48% of patients were between 10 and 13
      years old; 66.6% were boys. There was a incidence peak in September and October.
      Trauma locations were as follows: face (47.5%), ankle (17.9%), wrist (17.3%),
      knee (11.5%), and head trauma (12%). Eighty-five percent healed within 1 to 4
      weeks; 16.6% needed hospitalization. Fractures occurred in 31% of cases; 38% of
      these required surgical treatment. Concerning the mechanisms of injury, 45%
      occurred on the street and sidewalk, 44% of which resulted from collisions with a
      motor vehicle, 33% were caused by inefficient braking, and 15% were related to a
      mechanical problem with the scooter's structure. CONCLUSIONS: The authors
      observed a shift in the children's interest from roller skates toward the
      scooter. Research on scooter injury prevention needs to be improved, and a
      program needs to be promoted to reduce the number and the severity of related
      injuries. For now the authors would recommend head, mainly face, wrist, and ankle
      protections.

PMID- 11987095
TI  - New strategies in nonoperative management of meconium ileus.
AB  - PURPOSE: The aim of this study was to develop new nonoperative strategies for the
      management of meconium ileus in an attempt to improve on the current unacceptable
      failure rate. METHODS: Mice were constipated with subcutaneous morphine
      injection. Each then received an enema solution (perflubron, surfactant, Tween
      80, Gastrografin, Golytely, DNase, N-Acetylcysteine, Viokase, or normal saline).
      After the enema solution was administered, stool output was quantitated.
      Histologic examination of the intestines was performed on a second group of mice
      that also received enemas. Finally, viscosity measurements were taken of human
      meconium at baseline and after variable incubation periods with each test
      solution. RESULTS: For relieving constipation in vivo, Gastrografin enema was
      most efficacious. All agents were equally benign to the intestinal mucosa. In
      vitro, only 4% N-Acetylcysteine and perflubron were less effective at decreasing
      meconium viscosity than normal saline at T = 0 hours, with N-Acetylcysteine
      producing greater reduction in viscosity than normal saline at T = 6 hours.
      CONCLUSIONS: Our results show that surfactant and Gastrografin are the most
      effective for the in vivo relief of constipation. This is accomplished without
      mucosal damage. These agents also significantly reduce viscosity in vitro, and we
      speculate that they may be beneficial in relieving constipation caused by
      meconium ileus in cystic fibrosis patients.

PMID- 11987096
TI  - Epidermal growth factor improves nutritional outcome in a rat model of short
      bowel syndrome.
AB  - BACKGROUND/PURPOSE: This study investigates the effect of epidermal growth factor
      (EGF) on nutrient absorption in a rat model of short bowel syndrome (SBS).
      METHODS: Male juvenile rats underwent either transection (Sham) or ileocecal
      resection leaving a 20-cm jejunal remnant. Animals underwent follow-up for 10
      days, and resected animals were treated with placebo or recombinant human EGF (1
      53). Animals were pair fed; in vivo nutrient absorption, intestinal permeability,
      morphology, and total intestinal DNA and protein content were measured. RESULTS:
      Resected EGF-treated animals lost significantly less weight than those in the
      placebo group (-4.2 +/- 3 v -13.7 +/- 6.9%), absorbed significantly more 3-0
      methylglucose (76.8 +/- 6.6 v 64.9 +/- 10.1%), and had reduced permeability
      (lactulose/mannitol ratio, 0.35 +/- 0.19 v 0.60 +/- 0.20; P <.05 for all
      comparisons). CONCLUSIONS: These findings show that treatment of short bowel
      syndrome animals with EGF reduced weight loss and improved carbohydrate
      absorption and intestinal permeability. These findings suggest that enteral EGF
      may be a useful therapy for short bowel syndrome; further studies are indicated.

PMID- 11987097
TI  - Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.
AB  - BACKGROUND/PURPOSE: Neutropenic enterocolitis (typhlitis) is a common
      consideration after bone marrow transplantation. This study reviews the authors'
      experience with abdominal pain and typhlitis in an active pediatric bone marrow
      transplant program. METHODS: The Pediatric Bone Marrow Transplant Program
      Database was reviewed for patients presenting with abdominal pain or typhlitis.
      RESULTS: From 1993 to 2000 a total of 142 transplants have been performed. Of
      these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis.
      Nonspecific abdominal pain developed on the 12 +/- 11th day posttransplant,
      whereas patients in whom typhlitis developed were diagnosed on day 15.5 +/- 7.
      All patients were treated with prophylactic antibiotics consisting of acyclovir,
      fluconazole, and septra. With the onset of abdominal pain, 73 of 97 patients were
      placed on therapeutic antibiotics; patients identified with typhlitis had
      amphotericin plus GCSF added. No clinical features differentiated abdominal pain
      patients from typhlitis. Oral feeding and time of discharge was similar in both
      groups. Surgical intervention was not required, and no patients died with
      typhlitis. CONCLUSIONS: Abdominal pain is a common symptom after bone marrow
      transplant; however, typhlitis is relatively rare, and surgical intervention was
      not required in this series. Broad-spectrum (including fungal) antibiotic therapy
      appears to be an effective treatment for typhlitis in this patient population.

PMID- 11987098
TI  - A minimally invasive approach to bile duct injury after blunt liver trauma in
      pediatric patients.
AB  - A 12-year-old boy presented with a large liver laceration after blunt abdominal
      trauma. He was treated nonoperatively and subsequently had bile peritonitis from
      a bile leak. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the
      bile duct injury and allowed decompression of the biliary tree with an
      endoscopically placed biliary stent. A drain also was placed over the laceration
      through a small subcostal incision. The patient recovered rapidly after this
      minimally invasive procedure and went home 9 days later.

PMID- 11987099
TI  - Esophageal foreign body obstruction after esophageal atresia repair.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine the incidence and risk
      factors for esophageal foreign body obstruction (EFBO) after esophageal
      atresia/tracheoesophageal fistula (EA-TEF) repair. METHODS: A Case-control chart
      review was conducted from 1987 to 1999. RESULTS: EFBO occurred in 14 of 108
      patients (13%) with EA-TEF. Mean follow-up was 31 months. Alimentary debris was
      the most common foreign body. Mean time between operation and EFBO was 25 months.
      EFBO recurred in 50%. Sixty-one percent of patients required endoscopic FB
      removal. Esophageal stenosis was present in 57% of EFBO patients, and 80% of
      stenoses presented initially with EFBO. The incidence of gastroesophageal reflux
      (GER; 50%), type C anomaly (100%), anastomotic leak (21%), major associated
      anomalies (50%), and encephalopathy (14%) were not significantly different
      between the EFBO group and the total EA-TEF population. There was no difference
      in the need for antireflux surgery (57%) between those with EFBO and GER and the
      total EA/TEF population with GER. CONCLUSIONS: Esophageal foreign body
      obstruction occurs in at least 13% of patients after EA-TEF repair. Because no
      reliable risk factors were identified that could predict foreign body
      obstruction, all families should be warned about this possibility during the
      first 5 years, particularly once the child begins eating solid foods.

PMID- 11987100
TI  - Blunt renal trauma-blessing in disguise?
AB  - PURPOSE: The purpose of this study was to quantify pathologic lesions of the
      kidney found incidentally during the workup of a blunt renal trauma. METHODS: A
      retrospective review of the medical records of 103 patients ages 0 to 18 years
      with blunt renal injuries admitted to a level 1 pediatric trauma center between
      January 1, 1991 and December 31, 1999 was performed. All patients underwent
      ultrasonography and Doppler of their renal vessels. Additional investigations
      with computed tomography (CT) scan, cystography, or nuclear medicine functional
      studies were performed as indicated. RESULTS: Coexisting urogenital lesions were
      identified in 13 of 103 (12.6%) patients reviewed, and 7 (54%) required surgical
      treatment. The majority of the patients (9 of 13, 69%) suffered minimal trauma.
      All patients presented with gross hematuria as their main symptom. Stenosis of
      the uretero-pelvic junction was the most frequent diagnosis (n = 7): 3 patients
      required uretero-pyeloplasty, and 3 required nephrectomy. Two heterogeneous renal
      masses were discovered in which the diagnosis of a malignant process could not be
      eliminated; elective resection and open biopsy were performed. The diagnoses of
      multicystic kidney and solitary cyst with complex hematoma, respectively, were
      confirmed on pathology. Grade III ureterovesical reflux with pyelonephritis (n =
      1), polycystic kidney (n = 1), extrarenal pelvis without obstruction (n = 1), and
      horseshoe kidney (n = 1) were the other lesions discovered. CONCLUSIONS:
      Pathologic lesions of the urinary tract are uncommon; however, they may
      complicate an otherwise negligible renal trauma. The diagnostic and therapeutic
      approach to blunt renal trauma must be modified in these cases. A high index of
      suspicion must be maintained when a patient presents with gross hematuria with a
      minimal force blunt abdominal trauma.

PMID- 11987101
TI  - Percutaneous embolization of varicocele in children: A Canadian experience.
AB  - BACKGROUND/PURPOSE: The importance of early treatment of varicocele, to prevent
      testicular damage is widely accepted. Surgical treatment of varicocele has been
      the standard method of therapy, but recently a less invasive procedure was
      introduced and utilized mostly in Europe. The authors reviewed their experience
      with percutaneous embolization and sclerotherapy to assess the feasibility and
      outcome of this approach in children. METHODS: The authors conducted a
      retrospective study including all patients who underwent percutaneous
      embolization and sclerotherapy for varicocele in the authors' institutions for
      the last 10 years. Clinical data, investigation, pre and postintervention
      management, and the technique of the procedure, including sedation and anesthesia
      when needed, were collected from the charts. Follow-up was obtained from the
      chart or by phone. RESULTS: Between 1991 and 2001, 41 patients underwent 43
      percutaneous interventions. The median age was 14 years (range, 10 to 20 years).
      All but 2 were injected with a sclerosing agent; in 26 cases coils were added.
      All procedures except one were done under local anesthesia with sedation. Only 2
      patients were admitted overnight, and 5 patients had minor complications. The
      average procedure time was 55 minutes. Follow-up data were obtained in 39
      patients (95%), with a mean follow-up of 22 months. A total of 89.1% of those who
      were injected have satisfactory results (cured or improved) without the need for
      further procedures. Six patients required surgery post-percutaneous procedure, 4
      because of persistent or recurrent varicocele and 2 because of technical failure.
      CONCLUSIONS: Percutaneous embolization is a safe and effective treatment of
      varicocele in children with technical success in 95% and therapeutic success in
      89%. It now is the authors' first treatment modality for this disease.

PMID- 11987102
TI  - Intestinal energy metabolism after ischemia-reperfusion: Effects of moderate
      hypothermia and perfluorocarbons.
AB  - PURPOSE: This study investigated the roles of moderate hypothermia and
      extraluminal oxygenated perfluorcarbon (PFC) on intestinal metabolism after
      ischemia-reperfusion. METHODS: A model of 30-minute intestinal ischemia followed
      by 60 minutes of reperfusion was used. The animals were maintained at either
      normothermia (36.5 to 37.5 degrees C) or moderate hypothermia (31 to 32 degrees
      C). Four groups of adult rats were studied (n = 8 per group): (A) sham at
      normothermia, (B) ischemia-reperfusion at normothermia, (C) ischemia-reperfusion
      at hypothermia and, (D) ischemia-reperfusion with extraluminal oxygenated PFC
      perfusion during ischemia at normothermia. Intestinal phosphocreatine, ATP and
      lactate levels were measured. Histologic changes in the intestine were evaluated.
      RESULTS: Intestinal ischemia-reperfusion at normothermia caused a marked
      reduction in phosphocreatine and ATP with an increase in lactate. Moderate
      hypothermia exerted beneficial effects by attenuating the depletion of high
      energy phosphates and the elevation of lactate. Extraluminal PFC perfusion during
      ischemia failed to produce a protective effect on high-energy phosphates,
      although it reduced lactate accumulation. Moderate hypothermia significantly
      decreased the degree of mucosal damage. CONCLUSIONS: Whole-body moderate
      hypothermia protects the small intestine from reperfusion injury as measured both
      biochemically and histologically. Extraluminal oxygenated PFC administration
      during ischemia did not protect the intestine from reperfusion injury in this
      model.

PMID- 11987103
TI  - T cryptantigen activation is associated with advanced necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: Thomsen-Friedenreich cryptantigen activation (TCA) exposes
      neonates with necrotizing enterocolitis NEC to the risk of hemolysis after
      transfusion of blood products. The authors aimed to determine the prevalence of
      TCA in neonates with NEC and to correlate TCA with severity of disease and
      outcome. METHODS: One hundred four neonates with NEC were tested for TCA on
      admission. Patients with TCA requiring transfusion were given packed red cells,
      low-titer anti-T fresh frozen plasma, and washed platelets to avoid hemolysis.
      RESULTS: Twenty-three infants had TCA, and 96% of these had stage III disease.
      The incidence of TCA was significantly higher in infants with stage III disease
      compared with those with stage II (30% v 4%; P <.01). A total of 91% of infants
      with TCA required laparotomy compared with 81% of those with no activation. At
      laparotomy, widespread disease was more common in the TCA group (71% v 55%). TCA
      did not significantly increase mortality rate (TCA, 39% v no TCA, 28%); this may
      reflect the transfusion policy of our unit. CONCLUSIONS: Twenty-two percent of
      neonates with NEC referred to our unit had TCA. There is an association between
      TCA and advanced NEC. Screening of neonates with advanced NEC for TCA is advised
      to identify those at risk of hematologic complications.

PMID- 11987104
TI  - A rare case of colonic obstruction by 'cherry tomato' phytobezoar: A simple
      technique to avoid enterotomy.
AB  - Small bowel obstruction is the most common complication of phytobezoar in
      children. The authors present a rare case of colonic obstruction caused by a
      cherry tomato phytobezoar in a 16-month-old child that was treated successfully
      during laparotomy after failure of external fragmentation.

PMID- 11987105
TI  - Liposuction of a pediatric giant superficial lipoma.
AB  - Liposuction can be considered a preferable alternative to conventional surgery in
      pediatric lipomas that are bigger than 4 cm. Liposuction of pediatric lipomas has
      not been found in the English-language literature. The case of a 5-year-old girl
      who had liposuction of a large lipoma extending from the lower cervical to the
      right lumbar region is reported with a review of the literature on the technique,
      follow-up, and outcome of the procedure.

PMID- 11987106
TI  - Congenital lobar emphysema: Like father, like son.
AB  - Congenital lobar emphysema (CLE) is an uncommon cause of progressive respiratory
      distress that typically presents in the first few days of life. There has been a
      previous report of CLE in a mother and daughter. The authors describe 2 cases
      involving the right upper and middle lobes in a father and son secondary to
      relative deficiency of the bronchial cartilage. This provides additional evidence
      for inherited factors in the etiology of CLE.

PMID- 11987107
TI  - Internal hernia of the transverse colon-Chilaiditi syndrome in a child.
AB  - A redundant loop of transverse colon was herniated symptomatically behind the
      right liver to a suprahepatic, subdiaphragmatic position in an 11-year-old girl
      (Chilaiditi Syndrome). Constipation from birth, partial obstruction, and
      recurrent severe right upper quadrant pain unresponsive to nonoperative
      management warranted transverse colectomy.

PMID- 11987108
TI  - Duplication cyst of the duodenum as an unusual cause of massive gastrointestinal
      bleeding in an infant.
AB  - Duplication cysts of the gastrointestinal tract are rare and very rarely present
      as massive intestinal bleeding. The authors present a case in which massive
      bleeding was caused by a bleeding duodenal duplication cyst and was treated
      successfully by surgical excision. A review of the literature also is presented.

PMID- 11987109
TI  - Separation of xiphi-omphalo-ischiopagus tetrapus twins with favorable internal
      anatomy.
AB  - Conjoined twinning is a rare occurrence, and ischiopagus variety is even more
      rare. So far, only 20 cases have been reported. The incidence is 1 in 500,000.
      Because of its rarity and variable anatomy, no definite line of treatment can be
      adapted. Time of operation and mode of treatment have to be tailored according to
      the local circumstances and organ sharing in each individual pair. The twins in
      this report were xi phi-omphalo-ischiopagus tetrapus conjoined twins. Although
      several internal organs were fused and shared, they were complete mirror image
      sets for each twin. In this case report, details of anatomy and more importantly,
      preoperative investigations, preparations, and organizational aspects that were
      designed to suit local conditions are described. Operative details, postoperative
      care, and short and long-term progress also has been highlighted.

PMID- 11987110
TI  - Aneurysm of the inferior vena cava in a 5-year-old boy.
AB  - The authors present a case of an aneurysm of the inferior vena cava in a 5-year
      old boy. The boy suffered from acute pulmonary and paradoxical cerebral embolism
      after a minor abdominal trauma. Magnetic resonance angiography was the key for
      correct diagnosis of the retroperitoneal process and helped develop a strategy
      for surgery. The boy underwent resection of the aneurysm and a prosthetic
      replacement of the distal inferior vena cava. Aneurysms of the inferior vena cava
      are very rare conditions. The diagnosis is difficult because they may mimic a
      retroperitoneal tumor. Thrombosis and embolism are common complications of
      aneurysms of the vena cava.

PMID- 11987111
TI  - Congenital gastric teratoma with gastric perforation mimicking meconium
      peritonitis.
AB  - A case of congenital immature gastric teratoma along with spontaneous gastric
      perforation in a 1-day-old boy is presented. The clinical features are similar to
      those of meconium peritonitis. Coincidentally, the child had an arachnoid cyst at
      25 months of age. To the best of the authors knowledge, this case of congenital
      immature gastric teratoma associated with gastric perforation mimicking meconium
      peritonitis, is the first description in the English-language literature.

PMID- 11987112
TI  - Congenital cricopharyngeal achalasia: Diagnosis and surgical management.
AB  - BACKGROUND: Congenital cricopharyngeal achalasia is a rare condition in which a
      newborn presents with dysphagia, choking, nasal reflux, and salivation. Awareness
      of this condition is important because simple myotomy of the cricopharyngeus
      muscle often solves the problem. METHODS: The diagnosis and the surgical
      management of cricopharyngeal achalasia were reviewed based on 4 cases
      experienced over the last 13 years. RESULTS: The severity of the symptoms and the
      age of onset were dependent on the severity of achalasia. The cine-fluoroscopic
      swallow is an important diagnostic procedure. Surgery should be performed early
      enough for infants to learn how to swallow properly. The surgical procedure
      involves complete myotomy of cricopharyngeus, allowing the submucosa of the
      esophagus to bulge out in the posterior midline region. Postoperatively,
      nasopharyngeal reflux may resolve immediately or decrease over several months,
      depending on the timing of surgical intervention and the patient's ability to
      learn the act of swallowing. CONCLUSIONS: Early surgical intervention for this
      disease is recommended to achieve early recovery from dysphagia and to establish
      buccopharyngeal swallowing during the appropriate period of development.

PMID- 11987113
TI  - A patient with an unusual complication of sliding inguinal hernia: Stercoral
      appendiceal fistula.
AB  - An unusual case of sliding inguinal hernia complicated by stercoral appendicular
      fistula as a result of acute appendicitis was reported in a 3-month-old boy. A
      diagnosis was made using barium enema. Elective appendectomy and narrowing of the
      internal ring using a purse-string suture were carried out safely via a right
      transverse infraumblical incision. Postoperative follow-up was uneventful.

PMID- 11987114
TI  - Heterotopic gastric mucosa in the upper esophagus after repair of atresia.
AB  - One year after neonatal repair of esophageal atresia, a boy had intermittent mild
      dysphagia. Rigid esophagoscopy showed what was thought to be some inflammation at
      the level of the anastomosis but, at 5 years of age, with flexible esophagoscopy,
      this was identified as a ring of heterotopic gastric mucosa. This ring of mucosa
      has remained stable with surveillance up to 9 years of age. Although islands of
      heterotopic gastric mucosa in the esophagus are well recognized, there are no
      published reports of this at the level of an anastomosis for esophageal atresia
      with its associated clinical implications.

PMID- 11987115
TI  - Bladder dysfunction in children with bilateral single ectopic ureters.
AB  - BACKGROUND: Single ectopic ureters are a rare malformation in children. Therapy
      consists of ureteral reimplantation. However, in case of bilateral single ectopic
      ureters, subsequent malformation of the bladder trigone and bladder neck may
      result in additional voiding dysfunction, and ureteral reimplantation alone may
      not solve the urologic problems. METHODS: The authors report their experience
      with 2 girls, in whom bilateral single ectopic ureters were treated by ureteral
      reimplantation in early childhood and who did not gain adequate bladder control
      during following years. RESULTS: Videourodynamic evaluation was done in both
      girls. No bladder overactivity was found during the urodynamic studies. However,
      cystography showed a widely open bladder neck during filling with no sufficient
      bladder neck closure shown by urethral pressure profile studies. When blocking
      the bladder outlet by balloon catheters, adequate bladder filling volume was
      achieved. Incontinence was cured by implantation of an AMS 800 artificial
      sphincter system in a 10-year-old girl. A 7-year-old girl was regarded to be too
      young for sphincter implantation and is waiting for surgery within the next
      years. CONCLUSION: Insufficient development of trigone and bladder neck with
      subsequent urinary incontinence has to be kept in mind when deciding on surgical
      procedures in children with bilateral single ectopic ureters.

PMID- 11987122
TI  - High performance two-dimensional gel electrophoresis using a wetting agent
      Tergitol NP7.
AB  - Two-dimensional electrophoresis is an efficient method for the analysis of a
      broad range of complex protein samples. Current two-dimensional gel techniques
      are not suited for analysis of the small amount of proteins from tissue samples
      in the presence of high concentration of salts. Here we describe an improved two
      dimensional gel electrophoresis procedure based on the use of a nonionic wetting
      agent, Tergitol NP7, in rehydration solution combined with the application of a
      linear potential sweep during isoelectrofocusing. This experimental approach
      yields a dramatic increase in the resolution and focusing of proteins visualized
      on two-dimensional gels. This technique is less time-consuming and laborious than
      the current techniques and can be used for a variety of two-dimensional
      electrophoresis applications, including proteome analysis.

PMID- 11987123
TI  - An improved formulation of SYPRO Ruby protein gel stain: comparison with the
      original formulation and with a ruthenium II tris (bathophenanthroline
      disulfonate) formulation.
AB  - SYPRO Ruby protein gel stain is compatible with a variety of imaging platforms
      since it absorbs maximally in the ultraviolet (280 nm) and visible (470 nm)
      regions of the spectrum. Dye localization is achieved by noncovalent,
      electrostatic and hydrophobic binding to proteins, with signal being detected at
      610 nm. Since proteins are not covalently modified by the dye, compatibility with
      downstream proteomics techniques such as matrix-assisted laser
      desorption/ionisation-time of flight mass spectrometry is assured. The principal
      limitation of the original formulation of SYPRO Ruby protein gel stain, is that
      it was only compatible with a limited number of gel fixation procedures. Too
      aggressive a fixation protocol led to diminished signal intensity and poor
      detection sensitivity. This is particularly apparent when post-staining gels
      subjected to labeling with other fluorophores such as Schiff's base staining of
      glycoproteins with fluorescent hydrazides. Consequently, we have developed an
      improved formulation of SYPRO Ruby protein gel stain that is fully compatible
      with commonly implemented protein fixation procedures and is suitable for post
      staining gels after detection of glycoproteins using the green fluorescent Pro-Q
      Emerald 300 glycoprotein stain or detection of beta-glucuronidase using the green
      fluorescent ELF 97 beta-D-glucuronide. The new stain formulation is brighter,
      making it easier to manually excise spots for peptide mass profiling. An
      additional benefit of the improved formulation is that it permits staining of
      proteins in isoelectric focusing gels, without the requirement for caustic acids.

PMID- 11987124
TI  - Simultaneous red/green dual fluorescence detection on electroblots using BODIPY
      TR-X succinimidyl ester and ELF 39 phosphate.
AB  - A two-color fluorescence detection method is described based upon covalently
      coupling the succinimidyl ester of BODIPY TR-X dye to proteins immobilized on
      polyvinylidene difluoride membranes, followed by detection of target proteins
      using the fluorogenic, precipitating substrate ELF 39-phosphate in combination
      with alkaline phosphatase conjugated reporter molecules. This results in all
      proteins in the profile being visualized as fluorescent red signal while those
      detected specifically with the alkaline phosphatase conjugate appear as
      fluorescent green signal. The dichromatic detection system is broadly compatible
      with ultraviolet epi- or trans-illuminators combined with photographic or charge
      coupled device cameras, and xenon-arc sources equipped with appropriate
      excitation/emission filters. The dichromatic method permits detection of low
      nanogram amounts of protein and allows for unambiguous identification of target
      proteins relative to the entire protein profile on a single electroblot,
      obviating the need to run replicate gels that would otherwise require
      visualization of total proteins by silver staining and subsequent alignment with
      chemiluminescent or colorimetric signals generated on electroblots. Combining the
      detection approach with an Alexa Fluor 350 dye conjugated monoclonal antibody
      permits simultaneous fluorescence detection of two antigens and the total protein
      profile on the same electroblot.

PMID- 11987125
TI  - An accurate mass tag strategy for quantitative and high-throughput proteome
      measurements.
AB  - We describe and demonstrate a global strategy that extends the sensitivity,
      dynamic range, comprehensiveness, and throughput of proteomic measurements based
      upon the use of peptide "accurate mass tags" (AMTs) produced by global protein
      enzymatic digestion. The two-stage strategy exploits Fourier transform-ion
      cyclotron resonance (FT-ICR) mass spectrometry to validate peptide AMTs for a
      specific organism, tissue or cell type from "potential mass tags" identified
      using conventional tandem mass spectrometry (MS/MS) methods, providing greater
      confidence in identifications as well as the basis for subsequent measurements
      without the need for MS/MS, and thus with greater sensitivity and increased
      throughput. A single high resolution capillary liquid chromatography separation
      combined with high sensitivity, high resolution and accurate FT-ICR measurements
      has been shown capable of characterizing peptide mixtures of significantly more
      than 10(5) components with mass accuracies of < 1 ppm, sufficient for broad
      protein identification using AMTs. Other attractions of the approach include the
      broad and relatively unbiased proteome coverage, the capability for exploiting
      stable isotope labeling methods to realize high precision for relative protein
      abundance measurements, and the projected potential for study of mammalian
      proteomes when combined with additional sample fractionation. Using this
      strategy, in our first application we have been able to identify AMTs for >60% of
      the potentially expressed proteins in the organism Deinococcus radiodurans.

PMID- 11987126
TI  - Patchwork peptide sequencing: extraction of sequence information from accurate
      mass data of peptide tandem mass spectra recorded at high resolution.
AB  - The accurate mass values of all immonium, y(1), y(2), a(2), and b(2) ions of
      tryptic peptides composed of the 20 standard amino acids were calculated. The
      differences between adjacent masses in this data set are greater than 10 mDa for
      more than 80% of the values. Using this mass list, the majority of low mass ions
      in quadrupole-time of flight tandem mass spectra of peptides from tryptic digests
      and from an elastase digest could be assigned. Besides the a(2)/b(2) ions, which
      carry residues 1-2 from the N-terminus, a variety of internal dipeptide b ions
      were regularly observed. In case internal proline was present, corresponding
      dipeptide b ions carrying proline at the N-terminal position occurred. By
      assigning the dipeptide b ions on the basis of their accurate mass, bidirectional
      or unidirectional sequence information was obtained, which is localized to the
      peptide N-terminus (a(2)/b(2) ions) or not localized (internal b ions).
      Identification of the y(1) and y(2) ions by their accurate mass provides
      unidirectional sequence information localized to the peptide C-terminus. It is
      shown that this patchwork-type sequence information extractable from accurate
      mass data of low-mass ions is highly efficient for protein identification.

PMID- 11987127
TI  - Analysis of the proteome in the human pituitary.
AB  - The pituitary is the master endocrine gland responsible for the regulation of
      various physiologic and metabolic processes. Proteomics offers an efficient means
      for a comprehensive analysis of pituitary protein expression. This paper reports
      on the application of proteomics for the mapping of major proteins in a normal
      (control) pituitary. Pituitary proteins were separated by two-dimensional gel
      electrophoresis with immobilized pH 3-10 gradient strips. Major protein spots
      that were visualized in the two-dimensional gel by silver staining were excised,
      and the proteins in these spots were digested with trypsin. The tryptic digests
      were analyzed by mass spectrometry, and the mass spectrometric data were used to
      identify the proteins through searches of the SWISS-PROT or NCBInr protein
      sequence databases. The majority of the proteins were identified on the basis of
      peptide mass fingerprinting data obtained by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Several proteins were
      also characterized based on product-ion spectra measured by post-source decay
      analysis and/or liquid chromatography-electrospray-quadrupole ion trap mass
      spectrometry. To date, 62 prominent protein spots, corresponding to 38 different
      proteins, were identified. The identified proteins include important pituitary
      hormones, structural proteins, enzymes, and other proteins. The protein
      identification data were used to establish a two-dimensional reference database
      of the human pituitary, which can be accessed over the Internet
      (http://www.utmem.edu/proteomics). This database will serve as a tool for further
      proteomics studies of pituitary protein expression in health and disease.

PMID- 11987128
TI  - Proteomic analysis of rat soleus muscle undergoing hindlimb suspension-induced
      atrophy and reweighting hypertrophy.
AB  - A proteomic analysis was performed comparing normal rat soleus muscle to soleus
      muscle that had undergone either 0.5, 1, 2, 4, 7, 10 and 14 days of hindlimb
      suspension-induced atrophy or hindlimb suspension-induced atrophied soleus muscle
      that had undergone 1 hour, 8 hour, 1 day, 2 day, 4 day and 7 days of reweighting
      induced hypertrophy. Muscle mass measurements demonstrated continual loss of
      soleus mass occurred throughout the 21 days of hindlimb suspension; following
      reweighting, atrophied soleus muscle mass increased dramatically between 8 hours
      and 1 day post reweighting. Proteomic analysis of normal and atrophied soleus
      muscle demonstrated statistically significant changes in the relative levels of
      29 soleus proteins. Reweighting following atrophy demonstrated statistically
      significant changes in the relative levels of 15 soleus proteins. Protein
      identification using mass spectrometry was attempted for all differentially
      regulated proteins from both atrophied and hypertrophied soleus muscle. Five
      differentially regulated proteins from the hindlimb suspended atrophied soleus
      muscle were identified while five proteins were identified in the reweighting
      induced hypertrophied soleus muscles. The identified proteins could be generally
      grouped together as metabolic proteins, chaperone proteins and contractile
      apparatus proteins. Together these data demonstrate that coordinated temporally
      regulated changes in the skeletal muscle proteome occur during disuse-induced
      soleus muscle atrophy and reweighting hypertrophy.

PMID- 11987129
TI  - Proteomic analysis of cytokine induced proteins in human intestinal epithelial
      cells: implications for inflammatory bowel diseases.
AB  - A role for cytokine regulated proteins in epithelial cells has been suggested in
      the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was
      to identify such cytokine regulated targets using a proteomic functional
      approach. Protein patterns from (35)S-radiolabeled homogenates of cultured colon
      epithelial cells were compared before and after exposure to interferon-gamma,
      interleukin-1beta and interleukin-6. Proteins were separated by two-dimensional
      polyacrylamide gel electrophoresis. Both autoradiographies and silver stained
      gels were analyzed. Proteins showing differential expression were identified by
      tryptic in-gel digestion and mass spectrometry. Metabolism related proteins were
      also investigated by Western blot analysis. Tryptophanyl-tRNA synthetase,
      indoleamine-2,3-dioxygenase, heterogeneous nuclear ribonucleoprotein JKTBP,
      interferon-induced 35kDa protein, proteasome subunit LMP2 and arginosuccinate
      synthetase were identified as cytokine modulated proteins in vitro. Using
      purified epithelial cells from patients, overexpression of indoleamine-2,3
      dioxygenase, an enzyme involved in tryptophan metabolism, was confirmed in
      Crohn's disease as well as in ulcerative colitis, as compared to normal mucosa.
      No such difference was found in diverticulitis. Potentially, this observation
      opens new avenues in the treatment of IBD.

PMID- 11987130
TI  - Heat shock protein expression and anti-heat shock protein reactivity in renal
      cell carcinoma.
AB  - Heat shock proteins (HSP) are families of highly conserved proteins which are
      induced in cells and tissues upon exposure to extreme conditions causing acute or
      chronic stress. They exhibit distinct functions and have been implicated in the
      pathogenesis of a number of diseases, including cancer. A causal relationship
      between HSP expression and immunogenicity has been demonstrated in murine and
      human tumors and is also associated with the immune response. In order to
      investigate the correlation of HSP expression and their immunogenic potential in
      renal cell carcinoma (RCC), we here analyzed (i) the protein expression profile
      of various members of the HSP family in untreated and interferon (IFN)-gamma
      treated RCC cell lines as well as normal kidney epithelium, and (ii) the anti
      heat shock protein reactivity in sera derived from RCC patients and healthy
      controls using proteomics-based techniques. A heterogeneous expression pattern of
      members of the HSP families was demonstrated in RCC cell lines and in cells
      representing normal renal epithelium. In some cases the expression rate is
      moderately altered by IFN-gamma treatment. In addition, a distinct anti-heat
      shock protein reactivity could be detected in autologous and allogeneic sera from
      RCC patients and healthy controls. These data suggest that HSP play a role in the
      immunogenicity of RCC and thus might be used for the design of immunization
      strategies to induce a potent antitumor response in this disease.

PMID- 11987131
TI  - Effect of mild acid pH on the functioning of bacterial membranes in Vibrio
      cholerae.
AB  - In this paper, we initiated the first two-dimensional electrophoresis map of
      Vibrio cholerae, the aetiological agent of cholera disease. In this pathogen the
      efficient adaptation to detrimental conditions plays an important role in its
      survival in both the aquatic reservoir and human intestine. By proteome analysis
      we investigated the effect of mild acid treatment on the physiology of V.
      cholerae. More than 50 proteins were identified by matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry and database searching.
      Amongst them, pH regulated proteins belong to various functional classes such as
      intermediary metabolism and bacterial envelope. Several proteins whose
      accumulation level was decreased in response to acidic pH are known to be
      involved in the organization and the functioning of membranes, including
      lipopolysaccharide. Consistent with this, we observed an increased susceptibility
      to hydrophobic drugs, a loss of motility and a reduction in the ability to form a
      biofilm in cells grown at pH 6. Our results suggest that V. cholerae is able to
      sense a moderate decrease in pH and to modify accordingly its structure and
      physiology.

PMID- 11987132
TI  - Identification of vaccine candidate antigens of Staphylococcus aureus by
      serological proteome analysis.
AB  - In this study we applied serological proteome analysis (Klade, C. S. et al.
      Proteomics 2001, 1, 890-898) for identification of bacterial vaccine candidate
      antigens. First, approximately one hundred sera from healthy individuals and
      patients suffering from Staphylococcus aureus infections were screened for
      antibodies against staphylococcal lysates and recombinant proteins representing
      surface antigens. Two pools (healthy donors, patients) each consisting of five
      sera with the highest antiproteinaceous IgG reactivity were selected. Second, S.
      aureus COL was grown under different conditions and the number of antigens
      expressed was monitored by Western blot analysis. Third, surface proteins were
      enriched by digesting the bacterial cell wall under isotonic conditions and
      subsequent removal of protoplasts. These protein preparations were resolved by
      two-dimensional electrophoresis (2-DE) (pI 4-7). 2-DE immunoblotting using the
      preselected serum pools at 1:10 000-1:100 000 dilutions revealed a number of
      highly immunogenic staphylococcal proteins. Twenty-one spots were isolated by
      preparative 2-DE, and analysed by matrix-assisted laser desorption/ionization
      mass spectrometry and tandem mass spectrometry sequencing of tryptic peptides.
      This led to the identification of 15 proteins including known and novel vaccine
      candidates. Seroreactivity of several antigens including serine-aspartate repeat
      containing protein D, immuno-dominant staphylococcal antigen and a novel 309
      amino acid lipoprotein was independently confirmed by enzyme-linked immunosorbent
      assay and Western blot analysis of purified recombinant proteins. In conclusion,
      serological proteome analysis proved to be a powerful tool for the identification
      of novel staphylococcal antigens, which provide a basis for rational vaccine
      design.

PMID- 11987133
TI  - Stabilization of cell wall proteins in Bacillus subtilis: a proteomic approach.
AB  - Even though cell wall proteins of Bacillus subtilis are characterized by specific
      cell wall retention signals, some of these are also components of the
      extracellular proteome. In contrast to the majority of extracellular proteins,
      wall binding proteins disappeared from the extracellular proteome during the
      stationary phase and are subjected to proteolysis. Thus, the extracellular
      proteome of the multiple protease-deficient strain WB700 was analyzed which
      showed an increased stability of secreted WapA processing products during the
      stationary phase. In addition, stabilization of the WapA processing products was
      observed also in a sigD mutant strain which is impaired in motility and cell wall
      turnover. Next, we analyzed if proteins that can be extracted from B. subtilis
      cell walls are stabilized in the WB700 strain as well as in the sigD mutant.
      Thus, the cell wall proteome of B. subtilis wild type was defined showing most
      abundantly cell wall binding proteins (CWBPs) resulting from the WapA and WprA
      precursor processing. The inactivation of extracellular proteases as well as
      SigmaD caused an increase of CWBP105 and a decrease of CWBP62 in the cell wall
      proteome. We conclude that WapA processing products are substrates for the
      extracellular proteases which are stabilized in the absence of sigD due to an
      impaired cell wall turnover.

PMID- 11987137
TI  - Benefits of bioterrorism.

PMID- 11987138
TI  - Primate hepatitis B viruses - genetic diversity, geography and evolution.
AB  - There are six well characterised genotypes (A-F) of human hepatitis B virus that
      have distinct geographic ranges which generally relate to chronic HBV infection.
      A seventh human genotype (G) has recently been described, but there is limited
      information on ethnic and geographic distribution. Despite the fact that early
      studies indicated that HBV antigens were present in other primates, the
      prevailing dogma that HBV was a human disease precluded alternative explanations.
      Within the past 5 years, hepatitis B viruses have been characterised from all the
      Old World great apes (orangutan, gibbons, gorillas and chimpanzees) and from a
      New World woolly monkey. Each group of non-human primates appears to have a
      distinct strain of hepatitis B virus that can be distinguished from human
      sequences based upon the nucleotide sequence and selected amino acid changes in
      the viral proteins. The woolly monkey HBV is most divergent from other primate
      and human sequences, while the great ape HBV sequences cluster together with
      separate branches for each group.

PMID- 11987139
TI  - Clinical features of variant Creutzfeldt-Jakob disease.
AB  - Since 1996, over one hundred cases of variant Creutzfeldt-Jakob disease have
      appeared, mostly in the United Kingdom. In this review, we summarise the major
      clinical features of this progressive neurodegenerative condition and compare
      them with those of sporadic Creutzfeldt-Jakob disease. We emphasise the young age
      (median 26 years) at presentation and the dominant psychiatric/behavioural
      features, particularly depression. Sensory symptoms are present initially in half
      the cases and florid psychiatric symptoms, such as delusions or hallucinations,
      are also common. Given these symptoms, many patients present in clinical practice
      initially to a psychiatrist but are referred to neurologists when neurological
      signs become apparent. Although the definitive diagnosis remains
      neuropathological, a confident pre-mortem diagnosis is now possible when the
      'pulvinar sign' is seen on magnetic resonance imaging studies.

PMID- 11987140
TI  - TTV, a new human virus with single stranded circular DNA genome.
AB  - TT virus (TTV) was found in 1997 from a hepatitis patient without virus markers.
      However, the real impact of TTV on liver diseases remains uncertain to date. Due
      to the lack of suitable cell systems to support the growth of TTV, the biology of
      TTV is still obscure. This review tries to summarise the current status of TTV on
      aspects other than the taxonomic diversity of TTV. TTV was the first human virus
      with a single stranded circular DNA genome. TTV was considered to be a member of
      Circoviridae, but others suggested it conformed to a new family. TTV is distinct
      from ambisense viruses in the genus Circovirus, since the former genome is
      negative stranded. The genome structure of TTV is more related to chicken anaemia
      virus in the genus Gyrovirus, however, the sequence similarity is minimal except
      for a short stretch at 3816-3851 of TA278. Currently the working group is
      proposing the full name for TTV as TorqueTenoVirus and the TTV-like mini virus as
      TorqueTenoMiniVirus (TTMV) in a new genus Anellovirus (ring). TTVs are prevalent
      in non-human primates and human TTV can cross-infect chimpanzees. Furthermore,
      TTV sequences have been detected in chickens, pigs, cows and sheep. TTV can be
      transmitted by mother-to-child infection. However, within a year after birth, the
      prevalence reaches the same level for children born to both TTV-positive and TTV
      negative mothers even without breast-feeding. The non-coding region surrounding a
      short 113 nt GC-rich stretch and occupying approximately one-third of the genome
      is considered to contain the putative replication origin. Three mRNAs are
      expressed by TTV, 3.0 and 1.2 and 1.0 kb species. A protein translated from the
      3.0 kb mRNA is considered to be the major capsid protein as well as replicase.
      The nature of the proteins translated by the other two mRNAs are still putative.

PMID- 11987141
TI  - Functional balance between haemagglutinin and neuraminidase in influenza virus
      infections.
AB  - Influenza A and B viruses carry two surface glycoproteins, the haemagglutinin
      (HA) and the neuraminidase (NA). Both proteins have been found to recognise the
      same host cell molecule, sialic acid. HA binds to sialic acid-containing
      receptors on target cells to initiate virus infection, whereas NA cleaves sialic
      acids from cellular receptors and extracellular inhibitors to facilitate progeny
      virus release and to promote the spread of the infection to neighbouring cells.
      Numerous studies performed recently have revealed that an optimal interplay
      between these receptor-binding and receptor-destroying activities of the surface
      glycoproteins is required for efficient virus replication. An existing balance
      between the antagonistic HA and NA functions of individual viruses can be
      disturbed by various events, such as reassortment, virus transmission to a new
      host, or therapeutic inhibition of neuraminidase. The resulting decrease in the
      viral replicative fitness is usually overcome by restoration of the functional
      balance due to compensatory mutations in HA, NA or both proteins.

PMID- 11987142
TI  - Non-nucleoside inhibitors of herpesviruses.
AB  - While the treatment of herpes simplex virus with acyclovir and similar nucleoside
      analogues was one of the first success stories in antiviral chemotherapy,
      substantial unmet medical needs remain for herpesvirus diseases. In particular,
      the increasing numbers of immunosuppressed people due to AIDS, transplantation,
      cancer and aging has driven the need for improved antivirals to treat diseases
      caused by human cytomegalovirus (HCMV). Currently available drugs for the
      treatment of HCMV diseases are less than ideal agents due to issues of toxicity,
      modest efficacy and poor oral bioavailability. High throughput screening of large
      compound collections for inhibitors of specific viral enzymes or inhibition of
      viral growth in cell culture have identified a number of new HCMV inhibitors at
      several pharmaceutical companies. These compounds act by inhibition of novel
      molecular targets such as the viral protein kinase, viral protease and viral
      proteins involved in DNA cleavage/packaging. In addition, novel non-nucleoside
      inhibitors of the herpesvirus DNA polymerase have recently been described. This
      review will summarise some of these research efforts and will focus on non
      nucleoside compounds that directly inhibit a viral process.

PMID- 11987143
TI  - HIV integrase as a target for antiviral chemotherapy.
AB  - One of the three key enzymes encoded by the pol gene of HIV is a M(r) 32 000
      protein called HIV integrase. This viral enzyme is involved in the integration of
      HIV DNA into host chromosomal DNA. There appears to be no functional equivalent
      of the enzyme in human cells. The biochemical mechanism of integration of HIV DNA
      into the host cell genome involves a carefully defined sequence of DNA tailoring
      (3'-processing) and coupling (joining or integration) reactions. In spite of some
      effort in this area targeted at the discovery of therapeutically useful
      inhibitors of this viral enzyme, there are no drugs for HIV/AIDS in clinical use
      where the mechanism of action is inhibition of HIV integrase. Thus, new knowledge
      on inhibitors of this enzyme is of critical importance in the anti-HIV drug
      discovery area. The focus of this review will be on several classes of compounds,
      including nucleotides, dinucleotides, oligonucleotides and miscellaneous small
      molecules such as heterocyclic systems, natural products, diketo acids and
      sulfones, that have been discovered as inhibitors of HIV integrase. Special
      emphasis in the review will be placed on discoveries from my laboratory on HIV
      integrase inhibitors that are non-natural, nuclease-resistant dinucleotides.
      Comments on future directions and the prospects for developing integrase
      inhibitors as therapeutic antiviral agents are discussed.

PMID- 11987150
TI  - Silencing of pi-class glutathione S-transferase in MDA PCa 2a and MDA PCa 2b
      cells.
AB  - BACKGROUND: Loss of expression of the glutathione S-transferase-pi (GSTP1) is the
      most common genetic alteration described in human prostate cancer, occurring in
      virtually all tumors regardless of grade or stage. Of the available human
      prostate cancer cell lines, only LNCaP mirrors this phenotype. We investigated
      whether the prostate cancer cell lines MDA PCa 2a and MDA PCa 2b share this
      phenotype. METHODS: GSTP1 protein and mRNA levels were assessed in the MDA PCa 2a
      and MDA PCa 2b cell lines by Western and Northern blot. DNA methylation was
      evaluated by Southern blot analysis of genomic DNA digested with the methylation
      sensitive restriction enzymes BssHII, NotI, and SacII. Re-expression of GSTP1 was
      determined by RT-PCR following treatment with 5-azacytidine, a DNA
      methyltransferase inhibitor, and/or the histone deacetylase inhibitor
      trichostatin A (TSA). RESULTS: Like all human prostatic carcinomas in vivo, both
      the MDA PCa 2a and 2b cell lines lack protein and mRNA expression of GSTP1. This
      lack of expression is associated with methylation in the GSTP1 gene promoter.
      Treatment with the methyltransferase inhibitor 5-azacytidine resulted in re
      expression of GSTP1. By itself, TSA did not result in re-expression of GSTP1, nor
      did it augment expression induced by 5-azacytidine. CONCLUSIONS: MDA PCa 2a and
      2b appear to be useful models of human prostatic carcinoma in that they lack
      expression of GSTP1 due to gene silencing via promoter methylation. Inhibition of
      histone acetylation does not appear to affect GSTP1 expression.

PMID- 11987151
TI  - Contribution of death receptor and mitochondrial pathways to Fas-mediated
      apoptosis in the prostatic carcinoma cell line PC3.
AB  - BACKGROUND: Two main pathways of apoptosis in mammalian cells have been
      described: the death receptor pathway and the mitochondrial pathway. Two
      different cell types have been identified for Fas-mediated apoptosis, each using
      almost exclusively one of two different signaling pathways. Human prostatic
      carcinoma cell line, PC3 is sensitive to Fas-mediated apoptosis, but relation of
      receptor and mitochondrial pathways is not clear. METHODS: Cell viability was
      estimated by calcein assay. Apoptosis was determined by preparation of DNA
      ladder. Expression of Fas-associated death domain-dominant negative (FADD-DN) and
      Bcl-2, activation of caspases, PARP, DFF45, Bid cleavage, and cytochrome c
      release were assessed using Western blotting techniques. [(35)S] Methionine
      labeled caspase-3 was transcribed in vitro and translated using the TNT kit
      (Promega). A vector containing caspase-3 was prepared by the ligation of EcoR
      I/BamHI flanked PCR fragment of full size caspase-3 cDNA into pBlusckript II
      SK(+/-) (Stratagen). RESULTS: Overexpression of both FADD-DN and Bcl-2 genes
      prevent Fas-mediated apoptosis in PC3. As predicted, overexpression of FADD-DN
      prevented activation of caspase-8 and Bid cleavage and attenuated the release of
      cytochrome c and activation of caspases -2, -7, and -9. Bcl-2 overexpression did
      not affect caspase-8 activation and cleavage of Bid but blocked the release of
      cytochrome c and activation of mitochondria localized caspases -2, -7, and-9.
      Overexpression of FADD-DN and Bcl-2 affected the activation of caspase-3 and PARP
      cleavage differently: FADD-DN attenuated the activation of caspase-3 and PARP
      cleavage whereas Bcl-2 overexpression prevented caspase-3 activation and
      completely blocked cleavage of PARP. CONCLUSIONS: These data suggest that
      activation of caspase-8 is necessary but not sufficient to complete Fas-mediated
      apoptosis in PC3 cells without activation of the mitochondrial pathway. In
      addition, caspase-3 activation after Fas-receptor ligation involves two steps and
      is dependent on mitochondrial activation.

PMID- 11987152
TI  - Stat3 activation in prostatic carcinomas.
AB  - BACKGROUND: Activated Stat3 is found in various types of immortal cell lines and
      cancers. We and others have previously demonstrated that Stat3 is constitutively
      activated in rat and human prostate cancer cell lines, and that Stat3 activation
      is involved in IL-6-mediated signaling transduction in prostate cancer cells. The
      aim of this study is to examine quantitative Stat3 activity in benign and
      malignant human prostate tissues and analyze the association between Stat3
      activity levels and the clinical and pathologic parameters. METHODS: Stat3
      activity levels were analyzed in a total of 104 human primary prostate tissues
      using electromobility shift assay and immunohistochemical staining for
      phosphorylated Stat3. The tissue samples used were 42 prostate carcinomas, 42
      matched normal prostate tissues from patients with prostatic adenocarcinoma
      (normal adjacent to tumor), and 20 normal prostate tissues from organ donors.
      RESULTS: Significantly higher levels of constitutive Stat3 activity were detected
      in both prostate carcinomas and the matched normal prostate tissues adjacent to
      tumors compared to the normal prostates from donors without prostate cancer.
      There was no significant difference of Stat3 activity in foci of tumor and normal
      prostate tissue adjacent to tumor. No correlation was seen between Stat3 activity
      and Gleason grade or serum PSA levels in samples from prostate carcinomas.
      CONCLUSIONS: These results indicate that Stat3 is constitutively activated in
      prostate cancer. The high level of Stat3 activity in both the prostate carcinomas
      and the normal prostate tissues adjacent to tumors suggests that Stat3 activation
      may occur before detectable histological alterations of the prostate.

PMID- 11987153
TI  - Identification of differentially expressed genes associated with androgen
      independent growth of prostate cancer.
AB  - BACKGROUND: The human prostate cancer xenograft, CWR22, similar to most human
      prostate cancers, regresses after castration and recurs several months after the
      removal of androgen. Genes uniquely associated with proliferation were identified
      by comparison of tumors that exist in androgen absence but differ in
      proliferative capacity. METHODS: cDNA libraries from CWR22 tumors from 20-day
      castrate mice (proliferation undetectable) and recurrent CWR22 tumors
      (proliferation rate similar to androgen-dependent CWR22) were compared to
      evaluate the possibility that proliferation is triggered by either gain of
      function or loss of suppression. Differentially expressed genes were evaluated
      further for their temporal association with the onset of cellular proliferation
      using northern and western analysis and immunohistochemistry of a series of CWR22
      tumors that spanned the transition from androgen-dependent to recurrent growth.
      RESULTS: Subtractive hybridization identified 11 candidate genes from among 1,057
      clones examined. Northern analysis confirmed differential expression of 8 genes.
      Western analysis revealed an association between tomoregulin, translation
      elongation factor-1 alpha (EF-1 alpha), Mxi-1, and thioredoxin-binding protein
      2/vitamin D up-regulated protein, and the onset of recurrent growth.
      Immunohistochemistry revealed expression of tomoregulin, EF-1 alpha, Mxi-1, and
      thioredoxin reductase-1 coincidental with the onset of cellular proliferation on
      day 120 after castration. CONCLUSIONS: One or more of these genes may represent
      an appropriate target to prevent, delay or treat recurrent prostate cancer.

PMID- 11987154
TI  - Quantitative microbubble enhanced transrectal ultrasound as a tool for monitoring
      hormonal treatment of prostate carcinoma.
AB  - BACKGROUND: We quantified changes in prostate carcinoma vascularity treated with
      anti-androgens using color Doppler and power transrectal ultrasound in
      combination with microbubble contrast agent Levovist. METHODS: Thirty-six men
      with prostate carcinoma were studied at baseline and at intervals during
      treatment. At each attendance, Levovist((R)) (10 ml, 300 mg/ml) was given as an
      iv bolus. Using quantitative analysis, we calculated the pre-enhancement scores,
      arrival time, time to peak, peak value, and area under the time-enhancement curve
      (AUC). These were compared to pre-treatment values and serial PSA measurements.
      RESULTS: The pre-enhancement, peak value, and AUC each showed a marked response
      with reductions within one week. The average AUC declined to 68% +/- 9% (mean +/-
      standard error) by week 1, 56% +/- 9% by week 3, and 20% +/- 4% by week 6. A
      strong correlation with changes in the mean PSA (r = 0.95, P < 0.001) was also
      measured. In four patients, Doppler indices did not fall with PSA: two patients
      with the most marked discrepancy relapsed at 6 months. CONCLUSION: The vascular
      enhancement declined with therapy, similar to PSA. Microbubble enhanced
      ultrasound can show early response to treatment.

PMID- 11987155
TI  - Endoglin (CD105) is expressed on immature blood vessels and is a marker for
      survival in prostate cancer.
AB  - BACKGROUND: Endoglin, a receptor for some of the members of the transforming
      growth factor-beta (TGF-beta) family, is expressed on proliferating endothelial
      cells and has been suggested as a marker of ongoing angiogenesis. In this study,
      endoglin was evaluated as a prognostic factor for prostate cancer progression.
      METHODS: Immunohistochemical staining of endoglin was examined in 72 cases of
      prostate cancer and compared with immunohistochemical staining of the pan
      endothelial marker von Willebrand factor (vWf), clinicopathological factors, and
      cancer-specific survival. Micro-vessels were measured in the most vascularized
      fields. Double staining with antibodies against smooth muscle actin and endoglin
      or vWf, respectively, was performed in order to evaluate vessel maturation.
      RESULTS: Endoglin-stained tumor vessels were generally small and only 19% also
      stained with actin. Endoglin was a better prognostic marker than vWf. The median
      survival times were shorter for patients with tumor vascular count (vc) above
      median than for patients with vc below median (4 vs. 12 years, P = 0.0007, and 5
      vs. 10 years, P = 0.018, for endoglin and vWf, respectively). Endoglin vc was
      associated with Gleason score (P = 0.001), local tumor stage (P = 0.0006),
      metastasis (P = 0.01), tumor cell immunoreactivity for TGF-beta1 (P = 0.0003),
      and tumor cell proliferation index (r(s) = 0.319, P = 0.02). Endoglin, in
      contrast to vWf, vc was prognostic for survival in the subgroup of patients with
      Gleason score 5, 6, and 7 tumors. CONCLUSIONS: Endoglin marks principally small,
      probably newly formed tumor vessels in zthe prostate, and is a promising
      prognostic marker for prostate cancer patients.

PMID- 11987156
TI  - Worry and attitude of men in at-risk families for prostate cancer about genetic
      susceptibility and genetic testing.
AB  - BACKGROUND: The aim of this study was to evaluate worry about genetic
      susceptibility and the attitude of men with family history of prostate cancer
      (CaP) toward genetic testing. METHODS: Three hundred seventy-five eligible first
      degree relatives (FDR) of men with CaP, were asked to participate in a screening
      and to fill out a survey covering the worry about genetic susceptibility and
      interest in genetic testing. RESULTS: Of the 375 candidates contacted, 277
      completed the survey, and had undergone PSA measurement. Sixty-four percent
      worried a little or not at all about inherited predisposition to CaP, while the
      remainder worried a lot or extremely. The candidates who worried a lot or
      extremely were men with high levels of durable anxiety disposition (STAI trait),
      who had undergone a previous screening procedure and men with sons. Ninety-eight
      percent of men expressed their interest in undergoing genetic testing. The most
      motivated candidates to have the test done were men with several relatives with
      CaP. CONCLUSIONS: The level of worry about genetic susceptibility was low and
      there was a concrete interest in genetic testing in FDR of men with CaP. This
      interest increased with the number of CaP in the family.

PMID- 11987157
TI  - Relative promoter strengths in four human prostate cancer cell lines evaluated by
      particle bombardment-mediated gene transfer.
AB  - BACKGROUND: The particle bombardment (gene gun) method for gene transfer provides
      a new and efficient means for transfection of various cell types in culture. In
      this study we evaluate its application to human prostate tumor cells. METHODS:
      Transient expression of the firefly luciferase gene driven by five viral and five
      cellular promoters was assessed after in vitro gene transfer using the gene gun
      method. The relative strengths of these promoters were quantitatively determined
      in four different human prostate tumor cell lines: DU145, PC-3, LNCaP, and
      CWR22Rv1 cells. In situ histochemical staining of cells, transfected with
      bacterial beta-galactosidase cDNA as a reporter gene, was also performed to
      evaluate the transfection efficiency. Time course of gene expression was
      determined using the luciferase reporter gene. RESULTS: The peak levels of
      transient expression of firefly luciferase are observed within 24 hr after gene
      transfer. Sustained but reduced luciferase levels were also detected as long as 5
      days post transfection. Up to 35% of bombarded cells in vitro were found to
      express transgenic beta-galactosidase activity. Among tested viral promoters,
      cytomegalovirus early enhancer/promoter activity was observed to confer
      consistently the highest activity in each test cell line, whereas
      phosphoglycerate kinase gene promoter possessed the highest activity among the
      cellular promoters tested. CONCLUSIONS: The particle bombardment gene-transfer
      technology can be effectively employed as an efficient method for in vitro gene
      transfer into prostate tumor cells. The characterization of relative promoter
      strength and preference may be useful for future studies of cancer gene therapy
      approaches.

PMID- 11987158
TI  - Molecular recognition databases.

PMID- 11987159
TI  - Use of Relibase for retrieving complex three-dimensional interaction patterns
      including crystallographic packing effects.
AB  - Relibase is a database system that has been specially designed to handle protein
      ligand data. Included within Relibase is a tool that can be used to
      systematically analyse protein-ligand interaction patterns specified by three
      dimensional (3D) constraints, revealing favorable combinations of interacting
      functional groups and their preferred interaction geometries. This paper
      describes the Relibase 3D query tools, including novel extensions (Relibase+) for
      handling crystallographic packing effects. Examples illustrating the broad range
      of functionality for defining 3D interaction patterns and the application of such
      queries in drug design comprise carbonyl-carbonyl interactions, zinc binding site
      environments, and ligand-ligand interactions in the crystal packing.

PMID- 11987160
TI  - Automatic annotation of BIND molecular interactions from three-dimensional
      structures.
AB  - Software to automate the process of extracting molecular interactions from three
      dimensional (3D) structures has been developed that records these as Biomolecular
      Interaction Network Database (BIND) pairwise interaction records. Full annotation
      of BIND records is provided through a database processing tool called MMDBind,
      including detailed atom-atom and residue-residue level interaction information.
      BIND three-dimensional interaction annotation is synthesized by combining
      information from the Molecular Modeling Database (MMDB), and the HET (heterogen)
      group dictionary of small molecules in the macromolecular Crystallographic
      Information Format (mmCIF). Interactions are validated using the Protein
      Quaternary Structure (PQS) system. A total of 18,166 interactions were removed as
      being redundant or biologically irrelevant after PQS validation. This first pass
      MMDBind annotation creates two new divisions of BIND, 3D Biopolymers (BIND-3DBP)
      comprising 16,737 initial interaction records, and 3D Small Molecules (BIND-3DSM)
      comprising 48,219 records. Visualization of interacting residues and nucleotides
      within a macromolecular structure is possible directly from the BIND database
      owing to added 3D feature annotation within the BIND records that can be
      conveniently seen using Cn3D ("see-in-3D") after query from the BIND Data
      Manager. These interaction records provide a further demonstration of the
      completeness of the BIND data specification and its capabilities as storage and
      exchange format for all kinds of molecular interactions, including RNA, DNA,
      protein, and small molecules. Data from the 3DBP and 3DSM sets are available for
      downloading in Abstract Syntax Notation.1 (ASN.1) or Extensible Markup Language
      (XML) formats at ftp://ftp.bind.ca/DB/MMDBBind. Data from the 3DBP set is
      available for interactive query from the BIND Data Manager at www.bind.ca.

PMID- 11987161
TI  - Thermodynamic databases for proteins and protein-nucleic acid interactions.
AB  - Thermodynamic data regarding proteins and their interactions are important for
      understanding the mechanisms of protein folding, protein stability, and molecular
      recognition. Although there are several structural databases available for
      proteins and their complexes with other molecules, databases for experimental
      thermodynamic data on protein stability and interactions are rather scarce. Thus,
      we have developed two electronically accessible thermodynamic databases.
      ProTherm, Thermodynamic Database for Proteins and Mutants, contains numerical
      data of several thermodynamic parameters of protein stability, experimental
      methods and conditions, along with structural, functional, and literature
      information. ProNIT, Thermodynamic Database for Protein-Nucleic Acid
      Interactions, contains thermodynamic data for protein-nucleic acid binding,
      experimental conditions, structural information of proteins, nucleic acids and
      the complex, and literature information. These data have been incorporated into
      3DinSight, an integrated database for structure, function, and properties of
      biomolecules. A WWW interface allows users to search for data based on various
      conditions, with different display and sorting options, and to visualize
      molecular structures and their interactions. These thermodynamic databases,
      together with structural databases, help researchers gain insight into the
      relationship among structure, function, and thermodynamics of proteins and their
      interactions, and will become useful resources for studying proteins in the
      postgenomic era.

PMID- 11987162
TI  - The binding database: overview and user's guide.
AB  - The large and growing body of experimental data on molecular binding is of
      enormous value in biology, pharmacology, and chemistry. Applications include the
      assignment of function to biomolecules, drug discovery, molecular modeling, and
      nanotechnology. However, binding data are difficult to find and access because
      they are available almost exclusively through scientific journals. BindingDB, a
      public, web-accessible database of measured binding affinities, is designed to
      address this problem. BindingDB collects data for natural and modified
      biomolecules and for synthetic compounds, and provides detailed experimental
      information. Currently, measurements by isothermal titration calorimetry are
      fully supported; measurements by enzyme inhibition will soon be included as well.
      The web site allows data to be searched by a range of criteria, including binding
      thermodynamics, sequence homology, and chemical structure, substructure, and
      similarity. Experimentalists are encouraged to publicize their data by entering
      it into BindingDB via the online forms. Such data can be updated or revised by
      the depositor, if necessary, and will remain publicly accessible. User
      involvement and feedback are welcomed.

PMID- 11987177
TI  - Fluorescence spectroscopy and nucleic acids.

PMID- 11987178
TI  - The stretched DNA geometry of recombination and repair nucleoprotein filaments.
AB  - The RecA protein of Escherichia coli plays essential roles in homologous
      recombination and restarting stalled DNA replication forks. In vitro, the protein
      mediates DNA strand exchange between single-stranded (ssDNA) and homologous
      double-stranded DNA (dsDNA) molecules that serves as a model system for the in
      vivo processes. To date, no high-resolution structure of the key intermediate,
      comprised of three DNA strands simultaneously bound to a RecA filament (RecA x
      tsDNA complex), has been elucidated by classical methods. Here we review the
      systematic characterization of the helical geometries of the three DNA strands of
      the RecA x tsDNA complex using fluorescence resonance energy transfer (FRET)
      under physiologically relevant solution conditions. Measurements of the helical
      parameters for the RecA x tsDNA complex are consistent with the hypothesis that
      this complex is a late, poststrand-exchange intermediate with the outgoing strand
      shifted by about three base pairs with respect to its registry with the incoming
      and complementary strands. All three strands in the RecA x tsDNA complex adopt
      extended and unwound conformations similar to those of RecA-bound ssDNA and
      dsDNA.

PMID- 11987179
TI  - Time-resolved fluorescence resonance energy transfer: a versatile tool for the
      analysis of nucleic acids.
AB  - The biological functions of nucleic acids in processes of DNA replication,
      transcription, homologous recombination, mRNA translation, and ribozyme catalysis
      are intimately linked to their three-dimensional structures and to conformational
      changes induced by proteins, metal ions and other ligands. Fluorescence
      spectroscopy is a powerful technique for probing the structure and conformational
      dynamics of biological macromolecules under a wide range of solution conditions.
      Fluorescence resonance energy transfer (FRET) provides long-range distance
      information from 10 to 100 A, a range that is useful for probing the global
      structure of nucleic acids. While steady-state measurements of FRET provide the
      average distance between donor and acceptor, much more information is available
      from the analysis of the nanosecond emission decay of the donor in time-resolved
      FRET (trFRET) experiments. Analysis of the decay in terms of donor-acceptor
      distance distributions can resolve different conformers in a heterogeneous
      mixture, providing information on the global structure and flexibility of each
      species as well as their equilibrium populations. In this review, we outline the
      principles of trFRET and the methods used to incorporate fluorescent probes into
      DNA and RNA. Examples of specific applications are presented to illustrate the
      versatility of trFRET as a tool to define global structures, to identify
      conformational heterogeneity and flexibility, to investigate the energetics of
      tertiary structure formation and to probe structural rearrangements of nucleic
      acids.

PMID- 11987180
TI  - Time-resolved fluorescence resonance energy transfer studies of DNA bending in
      double-stranded oligonucleotides and in DNA-protein complexes.
AB  - Time-resolved Forster resonance energy transfer (trFRET) has been used to obtain
      interdye distance distributions. These distributions give the most probable
      distance as well as a parameter, sigma, that characterize the width of the
      distribution. This latter parameter contains information not only on the
      flexibility of the dyes tethered to macromolecules, but on the flexibility of the
      macromolecules. Both the most probable interdye distance as well as sigma provide
      insight into DNA static bending and DNA flexibility. Time-resolved fluorescence
      anisotropy and static anisotropy measurements can be combined to provide a
      measure of the cone angle within which the tethered dyes appear to wobble. When
      this motion is an order of magnitude faster than the average lifetime that
      characterizes transfer, an average value of the dipolar orientational parameter
      kappa2 can be calculated for various mutual dye orientations. The resulting
      kappa2 distribution is very much narrower than the limiting values of 0 and 4,
      allowing more precise distances and distance changes to be determined. Static and
      time-resolved fluorescence data can be combined to constrain the analyses of DNA
      protein kinetics to provide thermodynamic parameters for binding and for
      conformational changes along a reaction coordinate. The parameter sigma can be
      used to model multiple DNA-protein complexes with varying DNA bend angles in a
      global fitting of trFRET data. Such a global fitting approach has shown how the
      range of bends in single base DNA variants, when bound by the TATA binding
      protein (TBP), can be understood in terms of two limiting forms. Time-resolved
      FRET, combined with steady-state FRET, can be used to show not only how osmolytes
      affect the binding of DNA to proteins, but also how DNA bending depends on
      osmolyte concentration in the DNA-protein complexes.

PMID- 11987181
TI  - Fluorescence resonance energy transfer analysis of escherichia coli RNA
      polymerase and polymerase-DNA complexes.
AB  - Fluorescence resonance energy transfer (FRET) is a technique allowing
      measurements of atomic-scale distances in diluted solutions of macromolecules
      under native conditions. This feature makes FRET a powerful tool to study
      complicated biological assemblies. In this report we review the applications of
      FRET to studies of transcription initiation by Escherichia coli RNA polymerase.
      The versatility of FRET for studies of a large macromolecular assembly such as
      RNA polymerase is illustrated by examples of using FRET to address several
      different aspects of transcription initiation by polymerase. FRET has been used
      to determine the architecture of polymerase, its complex with single-stranded
      DNA, and the conformation of promoter fragment bound to polymerase. FRET has been
      also used as a binding assay to determine the thermodynamics of promoter DNA
      fragment binding to the polymerase. Functional conformational changes in the
      specificity subunit of polymerase responsible for the modulation of the promoter
      binding activity of the enzyme and the mechanistic aspects of the transition from
      the initiation to the elongation complex were also investigated.

PMID- 11987182
TI  - Fluorescence energy transfer monitored competitive equilibria of nucleic acids:
      applications in thermodynamics and screening.
AB  - Precise thermodynamic characterization of nucleic acid complex stability is
      required to understand a variety of biologically significant events as well as to
      exploit the specific recognition capabilities of nucleic acids in biotechnology,
      diagnostics, and therapeutics. The development of a database of nucleic acid
      thermodynamics with sufficient precision to foster further developments in these
      areas requires new and improved measurement techniques. The combination of a
      competitive equilibrium titration with fluorescence energy transfer based
      detection provides a method for precise measurement of differences in free energy
      values for nucleic acid duplexes that far exceeds in precision those accessible
      via conventional methods. The method can be applied to detect and to characterize
      any deviation in a nucleic acid that alters duplex stability. Such deviations
      include, but are not limited to, mismatches; single nucleotide polymorphisms
      (SNP); chemically modified nucleotide bases, sugars or phosphates; and
      conformational anomalies or folding motifs, such as, loops or hairpins.

PMID- 11987183
TI  - In the fluorescent spotlight: global and local conformational changes of small
      catalytic RNAs.
AB  - RNA is a ubiquitous biopolymer that performs a multitude of essential cellular
      functions involving the maintenance, transfer, and processing of genetic
      information. RNA is unique in that it can carry both genetic information and
      catalytic function. Its secondary structure domains, which fold stably and
      independently, assemble hierarchically into modular tertiary structures. Studies
      of these folding events are key to understanding how catalytic RNAs (ribozymes)
      are able to position reaction components for site-specific chemistry. We have
      made use of fluorescence techniques to monitor the rates and free energies of
      folding of the small hairpin and hepatitis delta virus (HDV) ribozymes, found in
      satellite RNAs of plant and the human hepatitis B viruses, respectively. In
      particular, fluorescence resonance energy transfer (FRET) has been employed to
      monitor global conformational changes, and 2-aminopurine fluorescence quenching
      to probe for local structural rearrangements. In this review we illuminate what
      we have learned about the reaction pathways of the hairpin and HDV ribozymes, and
      how our results have complemented other biochemical and biophysical
      investigations. The structural transitions observed in these two small catalytic
      RNAs are likely to be found in many other biological RNAs, and the described
      fluorescence techniques promise to be broadly applicable.

PMID- 11987238
TI  - Cholelithiasis in patients with Gaucher disease.
AB  - Gaucher disease, the inherited deficiency of the lysosomal enzyme
      glucocerebrosidase, manifests with a continually expanding range of clinical
      features. Noting that a number of adult patients with type 1 Gaucher disease also
      had gallstones, we reviewed the clinical records of 66 adult patients evaluated
      at the National Institutes of Health with type 1 Gaucher disease. Twenty-one
      patients were identified who had either gallstones or a history of
      cholecystectomy. Of the 21 patients, 6 were male. The age at which stones were
      noted ranged from 19 to 70 years (mean 39 years). Thirteen of the patients had a
      cholecystectomy performed. Several different factors may contribute to the
      development of gallstones in these patients, including anemia, prior splenectomy,
      and hepatic involvement. Eleven of the patients were found to have chronic
      anemia. Fifteen of the patients underwent splenectomy. An increased biliary
      excretion of glucosylceramide could also contribute to cholelithiasis. To
      determine whether our findings were specific to our referral population, the
      medical records of a second series of 80 adult patients of Ashkenazi Jewish
      ancestry with type 1 Gaucher disease followed in Northern Israel were reviewed.
      Sixteen of these patients (5 male, 11 female) were also noted to have gallstones.
      Thus, the frequency of gallbladder involvement in patients with Gaucher disease
      appears to be greater than previously appreciated.

PMID- 11987239
TI  - Identification of the presenilins in hematopoietic cells with localization of
      presenilin 1 to neutrophil and platelet granules.
AB  - Most cases of familial Alzheimer disease (AD) are caused by mutations in
      presenilin 1 (PS1) and presenilin 2 (PS2). Presenilins are required for the
      proteolytic processing of the beta amyloid precursor protein, which yields beta
      amyloid peptide, the major component of extracellular amyloid plaques. In
      addition, presenilins are essential for proteolytic processing of other membrane
      proteins, including Notch, TrkB, and APLP2. Notch directs neural and
      hematopoietic development. Here we show mRNA and protein expression of PS1 in
      both lymphoid and myeloid cells, while PS2 mRNA is present only in lymphocytes.
      Expression of PS1 was found throughout myeloid development from CD34+ stem cells
      to platelets and neutrophils. PS1 expression was found in avian as well as
      mammalian blood cells. In neutrophils, PS1 colocalized with myeloperoxidase and
      CD63 within the azurophil granules as demonstrated by subcellular fractionation
      and double labeling immunogold electron microscopy. In platelets, PS1 colocalized
      with glucose transporter (GLUT-3) in the membrane of alpha granules, as evidenced
      by immunogold electron microscopy. The colocalization of PS1 and amyloid
      precursor protein in cell-specific granules suggests a conserved function across
      different tissues. These studies indicate that PS1 may play multiple roles in
      blood cell physiology and that blood tissue may provide a model to study PS1
      interactions with other proteins.

PMID- 11987240
TI  - Functional role of the four different types of (AT)(x)T(y) motifs 5' to the beta
      globin gene and their distribution in the Greek population.
AB  - The polymorphic sequence (AT)(X)T(Y) motif residing 0.5 kb 5' to the human 
      globin gene has been shown to be a binding site for a putative repressor protein,
      BP1, in K562 cells. The (AT)(X)T(Y) sequence is characterized by variable length
      and several configurations. The precise role of the (AT)(X)T(Y) repeats on the
      regulation of the -globin gene remains unclear. In the present study, we
      identified the (AT)(X)T(Y) motifs which prevail in the Greek population,
      established their frequency, and directly investigated their role on -globin gene
      expression by comparing the effects of the four identified (AT)(X)T(Y) motifs
      using transient expression assays. Four different configurations were found in
      the Greek population: the (AT)7T7 motif was the most abundant (81.8%)
      representing the reference sequence, the (AT)9T5 motif (16.1%), and the (AT)11T3
      motif (2%), while the (AT)8T4 motif was absent from normal A chromosomes and was
      exclusively found on s chromosomes. To evaluate their different role on
      transcriptional regulation, the four motifs were subcloned upstream of the
      luciferase reporter gene. Two expression systems were used; MEL cells were
      transfected with a pGL-2 basic plasmid containing one of the four (AT)(X)T(Y)
      repeats, the -globin gene promoter, and the luciferase gene, while HeLa cells
      were transfected with a similar construct (pGL-2 enhancer) including the SV40
      enhancer. After 48 h following transient transfection of the cell lines, the
      expression level of the reporter gene was estimated using a photoilluminometer.
      The transfected MEL cells exhibited a clearly reduced expression of the
      luciferase gene driven by the -globin promoter containing the (AT)9T5 and
      (AT)11T3 configurations. In contrast, HeLa cells did not exhibit any differences
      among the four motifs. On the basis of these results, we postulate that the
      (AT)9T5 and (AT)11T3 variants residing 0.5 kb 5' to the -globin gene do not
      represent simple polymorphisms and can affect its expression in an erythroid
      environment.

PMID- 11987241
TI  - Methylthioadenosine phosphorylase as target for chemoselective treatment of T
      cell acute lymphoblastic leukemic cells.
AB  - We analyzed the role of methylthioadenosine phosphorylase (MTAP) for
      chemoselective treatment of T-cell acute lymphoblastic leukemia (T-ALL). MTAP
      converts methylthioadenosine into adenine which serves as an alternative purine
      source, if de novo purine biosynthesis is inhibited by antimetabolites (i.e.,
      methotrexate). The idea of the chemoselectivity concept is that tumors with MTAP
      deletion at chromosome 9p21 are more susceptible to antimetabolites than normal
      cells without such a deletion. First, we screened 13 T-ALL lines for 9p21
      deletions by comparative genomic hybridization. Five cell lines revealed
      deletions at the short arm of chromosome 9, dim(9p21pter). Further analyses were
      performed with CEM cells in which the 9p21 deletion was corroborated by
      fluorescence in situ hybridization. CEM cells were transfected with an MTAP
      expression vector. A green fluorescent protein (GFP) plasmid was cotransfected,
      to monitor the transfection efficacy by flow cytometry. The response of MTAP
      transfected cells to the antimetabolites methotrexate (MTX), trimetrexate (TMX),
      and L-alanosine (ALA) was decreased compared to mock control transfectants using
      growth inhibition assays. The activity of doxorubicin (DOX) which is not involved
      in DNA biosynthesis was not changed in MTAP transfectants. As the p16(INK4a)
      tumor suppressor gene resides also at 9p21, we transfected CEM cells with a
      p16(INK4a) expression vector. These transfectant cells were more resistant to all
      four drugs indicating that p16(INK4a) did not specifically affect
      antimetabolites. The chemoselective effect of antimetabolites in MTAP-deleted
      tumor cells may, however, be compensated by the development of drug resistance.
      To prove this possibility, we analyzed an MTX-resistant subline, CEM/MTX1500LV,
      in which the MTX-resistance conferring dihydrofolate reductase (DHFR) gene was
      amplified. While TMX exhibited considerable cross-resistance in CEM/MTX1500LV
      cells, ALA did not. Thus, ALA could exhibit chemoselectivity in 9p21/MTAP-deleted
      cells, even if DHFR amplification occurs. We conclude that ALA may be more
      suitable than MTX or TMX for MTAP-mediated chemoselective treatment of T-ALL.
      Pretherapeutical detection of 9p21 and MTAP deletion may be helpful in developing
      a predictive molecular chemosensitivity test for T-ALL.

PMID- 11987242
TI  - Endemic polycythemia in Russia: mutation in the VHL gene.
AB  - Chuvash polycythemia (CP) is an autosomal recessive condition that is endemic in
      the Russian mid-Volga River region of Chuvashia. We previously found that CP
      patients may have increased serum erythropoietin (EPO) levels, ruled out linkage
      to both the EPO and EPO receptor (EPOR) gene loci, and hypothesized that the
      defect may lie in the oxygen homeostasis pathway. We now report a study of five
      multiplex Chuvash families which confirms that CP is associated with significant
      elevations of serum EPO levels and rules out a location for the CP gene on
      chromosome 11 as had been reported by other investigators or a mutation of the
      HIF-1 alpha gene. Using a genome-wide screen, we localized a region on chromosome
      3 with a LOD score >2. After sequencing three candidate genes, we identified a C
      to T transition at nucleotide 598 (an R200W mutation) in the von Hippel-Lindau
      (VHL) gene. The VHL protein (pVHL) downregulates the alpha subunit of hypoxia
      inducible factor 1 (HIF-1 alpha), the main regulator of hypoxia adaptation, by
      targeting the protein for degradation. In the simplest scenario, disruption of
      pVHL function causes a failure to degrade HIF-1 alpha resulting in accumulation
      of HIF-1 alpha, upregulation of downstream target genes such as EPO, and the
      clinical manifestation of polycythemia. These findings strongly suggest that CP
      is a congenital disorder of oxygen homeostasis.

PMID- 11987243
TI  - A bipartite NLS at the SHP-1 C-terminus mediates cytokine-induced SHP-1 nuclear
      localization in cell growth control.
AB  - SHP-1 protein tyrosine phosphatase is a critical regulator of signaling in
      hematopoietic cells as illustrated by the lethal hematopoietic disorders in SHP-1
      deficient mice. We and others have shown in previous studies that SHP-1 regulates
      membrane receptor signaling: it binds via its N-terminal region SH2 domains to
      tyrosine phosphorylated membrane receptors to dephosphorylate key substrates in
      the receptor complexes. Here we demonstrate that the SHP-1 C-terminal region
      contains a bipartite NLS that mediates SHP-1 nuclear localization in response to
      cytokines. This NLS was located within amino acids 576-595 of the PTPase and,
      when fused by itself to EGFP, targeted the fluorescent protein into the nuclei of
      transiently transfected NIH3T3 fibroblasts and Bac1.2f5 macrophage cells. When
      positioned within SHP-1, the activity of the NSL was under tight regulation as
      indicated by the predominant cytoplasmic distribution of the EGFP/SHP-1 fusion
      protein in NIH3T3 transfectants and the exclusive cytoplasmic localization of the
      endogenous SHP-1 in hematopoietic cell line PBLC-1. Activation of the NLS in SHP
      1 by IL-4 was demonstrated by increased nuclear localization of the EGFP/SHP-1
      fusion protein in NIH3T3 transfectants and of the endogenous SHP-1 protein in
      PBCL-1 cells at 4, 6 and 8 h post-IL-4 stimulation. SHP-1 nuclear localization in
      PBCL-1 cells was also induced by IL-7 in a similar manner, suggesting it as a
      common event in cytokine signaling. In comparison to that of the wild-type
      phosphatase, an SHP-1 mutant lacking the NLS showed only approximately half of
      the activity in inhibiting proliferation of NIH3T3 transfectants. These results
      provide evidence of cytokine-regulated SHP-1 nuclear localization mediated by a
      bipartite NLS and suggest that SHP-1 regulates nuclear signaling in cell growth
      control.

PMID- 11987244
TI  - Determination of alpha-1 acid glycoprotein in patients with Ph+ chronic myeloid
      leukemia during the first 13 weeks of therapy with STI571.
AB  - The tyrosine kinase activity of the BCR/ABL fusion protein is required for the
      transformation in patients with chronic myeloid leukemia. The tyrosine kinase
      inhibitor STI571 inhibits the BCR/ABL and ABL kinase activity and consequently
      inhibits growth of BCR/ABL-positive cells. However, resistance to STI571 has been
      demonstrated in Ph+ cell lines and in CML patients and can be explained in some
      cases by point mutations within the ATP-binding pocket or amplification of the
      bcr/abl gene. In previous investigations using a nu/nu mouse model, the binding
      of STI571 to elevated levels of the plasmaprotein -1 acid glycoprotein (AGP) was
      identified as an additional mechanism of resistance to this therapeutic approach.
      Here we provide data on the expression of AGP in CML patients under therapy with
      STI571. Patients received 400 or 600 mg STI571 daily and apart from clinical
      parameters we determined AGP and C-reactive protein (CRP) plasma levels as well
      as the quantitative expression of both BCR/ABL and AGP mRNA in peripheral blood
      cells. Our data suggest that despite elevated AGP levels in 52% of our patients,
      no upfront resistance against STI571 was present. In conclusion, we demonstrated
      that during the first 13 weeks of STI571 therapy (i) plasma AGP levels in CML
      patients correlate with white blood cell count and stage of disease; (ii)
      patients with elevated AGP responded less rapidly to STI571; (iii) elevated AGP
      and CRP levels normalized in patients during treatment with STI571, although mRNA
      levels of AGP remained stable; (iv) initially normal levels of AGP remained in
      the normal range during treatment with STI571, indicating that STI571 does not
      trigger AGP expression in humans; and (v) in relapsed patients, elevation of AGP
      levels is present prior to hematological progress.

PMID- 11987246
TI  - Chest X-ray quiz. Left-to-right shunt.

PMID- 11987245
TI  - Genotyping by"cold single-strand conformation polymorphism" of the UGT1A1
      promoter polymorphism in Mexican mestizos.
AB  - Since no data have previously been reported concerning both the (TA) n
      polymorphism at the promoter of the UGT1A1 gene in the Mexican population and the
      use of single-strand conformation polymorphism (SSCP) for the detection of such
      polymorphism, genotyping by SSCP in 375 G-6-PD normal (Group A) and 81 G-6-PD
      deficient (Group B) mestizos belonging to 14 states was carried out. Allele
      frequencies for (TA)6 and (TA)7 repeats were 0.654 and 0.334, respectively, in
      Group A and 0.685 and 0.315 in Group B; in the former group, the (TA)5 allele was
      also observed with a frequency of 0.012. The frequencies of the genotype
      (TA)7/(TA)7 were 10.1% (Group A) and 8.6% (Group B). The (TA)7/(TA)8 genotype was
      also observed in a patient with unconjugated hyperbilirubinemia. Due to the
      importance of its potential medical implications, the observed high frequency
      (10%) of the (TA)7/(TA)7 genotype is stressed. Genotyping by SSCP of the (TA) n
      polymorphism is an adequate methodological option.

PMID- 11987247
TI  - A hymn to morphine.

PMID- 11987248
TI  - Bibliography. Current world literature. Glaucoma.

PMID- 11987253
TI  - The Congo children's weeping sores.

PMID- 11987254
TI  - Women don't get heart attacks?

PMID- 11987255
TI  - Toxic waste. Deep in the roots of nursing comes a search for harmful sources.

PMID- 11987256
TI  - Research shows erosion to advocacy role.

PMID- 11987257
TI  - Conquering chronic anger.

PMID- 11987258
TI  - Clinicians use group-wise effort for innovations.

PMID- 11987259
TI  - Nurses report widespread ethical conflicts.

PMID- 11987260
TI  - Patients teach spirit of nursing.

PMID- 11987261
TI  - Suffering. Nurses heeding the call.

PMID- 11987262
TI  - Evolution of colorectal cancer: change of pace and change of direction.
AB  - This review compiles evidence for an alternative to the classical adenoma
      carcinoma sequence in the evolution of colorectal cancer. It is suggested that
      between 30 and 50 of colorectal cancers are not initiated by mutation of the
      tumor suppressor gene APC, but through the epigenetic silencing of genes
      implicated in the control of differentiation, cell cycle control and DNA repair
      proficiency. The precursor polyps are often characterized by a serrated
      architecture, and include hyperplastic polyps, admixed polyps and serrated
      adenomas. The alternative pathway is heterogeneous and may culminate in cancers
      showing low or high level DNA microsatellite instability (MSI-L and MSI-H,
      respectively), and in cancers that are microsatellite stable (MSS). Cancers
      showing DNA MSI may be characterized by an accelerated evolution. Cancers in
      hereditary non-polyposis colorectal cancer show features of both classical
      (adenoma and APC mutation) and alternative pathways (rapid evolution, MSI-H and
      lack of chromosomal instability).

PMID- 11987263
TI  - Reinfection rate following effective therapy against Helicobacter pylori
      infection in Japan.
AB  - BACKGROUND AND AIM: In developed countries, reinfection of Helicobacter pylori
      (H. pylori) after eradication of the bacterium is unusual, while the reinfection
      rate in developing countries is variable. In this study, we determined the
      reinfection rate after successful H. pylori eradication in Japan, a country with
      a high prevalence of H. pylori infection. METHODS: After successful eradication,
      377 patients were followed up by endoscopy and urea breath test annually. In
      reinfected patients, H. pylori strains isolated initially and after reinfection
      were compared by using random amplification of polymorphic DNA fingerprinting.
      RESULTS: H. pylori became positive in four of 337 patients (1.2) 1 year after
      eradication and in two of 133 patients (1.5) 2 years after eradication. One
      patient experienced an ulcer relapse 2 years after eradication therapy. Random
      amplification of polymorphic DNA fingerprinting of the isolated strains from four
      of the six patients showed two had identical strains (at 1 year) while the other
      two had different strains (one at 1 year and one at 2 years). When infection in
      the two patients reinfected with identical strains is considered a recrudescence,
      the true reinfection rate is < 0.8 per patient year. CONCLUSIONS: The reinfection
      rate after eradication of H. pylori is low in Japan despite the country's high
      prevalence of H. pylori infection.

PMID- 11987264
TI  - Proceedings of the 8th Conference on Frontiers of Electron Microscopy in
      Materials Science. Shimane, Japan, November 13-17, 2000.

PMID- 11987265
TI  - Pain relief in pregnancy is a lottery.

PMID- 11987267
TI  - Using information technology to improve the patient's experience.

PMID- 11987268
TI  - Management tools. Results-oriented decision making.

PMID- 11987269
TI  - [UEMS--European Board of Pediatric Surgery specialty examination].

PMID- 11987270
TI  - [Could it be a little more? Education of surgeons in Hungary in comparison with
      Europe].

PMID- 11987271
TI  - [Education of surgeons in Hungary].

PMID- 11987272
TI  - Portal vein and splenic vein thrombosis.

PMID- 11987273
TI  - 50 ways to enhance your career.

PMID- 11987274
TI  - Choristoma of the optic nerve: case report.
AB  - OBJECTIVE AND IMPORTANCE: Optic nerve choristoma is a rare lesion composed of
      adipose tissue and smooth muscle involving the optic nerve. Few cases have been
      reported. CLINICAL PRESENTATION: A 20-year-old woman presented with a history of
      slowly progressive visual loss in the left eye. On T1-weighted magnetic resonance
      imaging studies, after frequency-selective fat saturation, an optic nerve mass
      was detected at the level of the optic canal with signal characteristics
      suggesting the diagnosis of optic nerve lipoma. INTERVENTION: At left
      frontotemporal craniotomy, the intracranial optic nerve appeared thin and
      atrophic proximally and was covered by abundant adipose tissue distally. Because
      no cleavage plane could be identified between the fatty lesion and the optic
      nerve, which appeared splayed within the adipose tissue, the nerve was resected
      after an intraoperative biopsy. The presence of two heterotopic mesodermal
      elements, a rim of adipose tissue admixed with bundles of mature smooth muscle,
      extending into the nerve septa, warranted a diagnosis of optic nerve choristoma.
      CONCLUSION: Optic nerve choristoma is an uncommon optic nerve lesion. Even if
      imaging studies are highly suggestive of the diagnosis, pathological confirmation
      is required because of the high adipose tissue content in the majority of cases.
      The lesion, most likely malformative and nonneoplastic in nature, can be the
      cause of progressive visual loss.

PMID- 11987275
TI  - Vitoss bone substitute.

PMID- 11987276
TI  - C1-C2 transarticular screw fixation for atlantoaxial instability: a 6-year
      experience, and C1-C2 transarticular screw fixation--technical aspects.

PMID- 11987277
TI  - Posterior fossa decompression and clot evacuation for fourth ventricle hemorrhage
      after aneurysmal rupture: case report.

PMID- 11987278
TI  - Clinical manifestations and survival rates among patients with saccular
      intracranial aneurysms: population-based study in Olmsted County, Minnesota, 1965
      to 1995.

PMID- 11987279
TI  - New method for obliterative treatment of an anterior wall aneurysm in the
      internal carotid artery: encircling silicone sheet clip procedure--technical case
      report.

PMID- 11987280
TI  - Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal
      subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study.

PMID- 11987281
TI  - Easy sellar reconstruction in endoscopic endonasal transsphenoidal surgery with
      polyester-silicone dural substitute and fibrin glue: technical note.

PMID- 11987282
TI  - Focal intracranial infections due to Propionibacterium acnes: report of three
      cases.

PMID- 11987283
TI  - Collagen sponge repair of small cerebrospinal fluid leaks obviates tissue grafts
      and cerebrospinal fluid diversion after pituitary surgery.

PMID- 11987284
TI  - Microelectromechanical systems and neurosurgery: a new era in a new millennium.

PMID- 11987285
TI  - Bibliography. Current world literature. Anabolic and catabolic signals.

PMID- 11987286
TI  - Bibliography. Current world literature. Technical aspects of nutritional support.

PMID- 11987287
TI  - Guidelines. American Academy of Pediatric Dentistry.

PMID- 11987288
TI  - Oral health policies. American Academy of Pediatric Dentistry.

PMID- 11987289
TI  - [Manual for the professional accreditation of excellence in angiology].

PMID- 11987290
TI  - North American Society of Pacing and Electrophysiology 23rd Annual Scientific
      Sessions. May 8-11, 2002. San Diego, California, USA. Abstracts.

PMID- 11987291
TI  - Abstracts of the 8th International Symposium on Interventional Radiology and New
      Vascular Imaging and the 31st Annual Meeting of the Japanese Society of
      Angiography and Interventional Radiology. Tokyo, Japan, May 10-12, 2002.

PMID- 11987292
TI  - Abstracts of the 22nd International Symposium on Intensive Care and Emergency
      Medicine. Brussels, Belgium, 19-22 March 2002.

PMID- 11987293
TI  - Abstracts of the Sylvester O'Halloran Surgical Scientific Meeting. 8-9 March
      2002, University of Limerick.

PMID- 11987294
TI  - American Society of Nephrology 32nd Annual Meeting and the 1999 Renal Week.
      November 1-8, 1999, Miami Beach, Florida, USA. Abstracts.

PMID- 11987295
TI  - From the Centers for Disease Control and Prevention. Enterobacter sakazakii
      infections associated with the use of powdered infant formula--Tennessee, 2001.

PMID- 11987296
TI  - From the Centers for Disease Control and Prevention. Progress toward elimination
      of Haemophilus influenzae type b invasive disease among infants and children--
      United States, 1998-2000.

PMID- 11987298
TI  - Abstracts of the 3rd European Breast Cancer Conference. 19-23 March 2002.
      Barcelona, Spain.

PMID- 11987297
TI  - From the Centers for Disease Control and Prevention. Variation in homicide risk
      during infancy--United States, 1989-1998.

PMID- 11987301
TI  - An interview with Giel Vaessen.

PMID- 11987303
TI  - Mars inflatable greenhouse analog.
AB  - Light intensities on the Martian surface can possibly support a bioregenerative
      life support system (BLSS) utilizing natural sunlight for hydroponic crop
      production, if a suitable controlled environment can be provided. Inflatable
      clear membrane structures offer low mass, are more easily transported than a
      rigid structure, and are good candidates for providing a suitable controlled
      environment for crop production. Cable culture is one hydroponic growing system
      that can take advantage of the beneficial attributes of the inflatable structure.
      An analog of a Mars inflatable greenhouse can provide researchers data on issues
      such as crew time requirements for operation, productivity for BLSS, human
      factors, and much more at a reasonable cost. This is a description of one such
      design.

PMID- 11987302
TI  - Toward Martian agriculture: responses of plants to hypobaria.
AB  - The recent surge of interest in human missions to Mars has also generated
      considerable interest in the responses of plants to hypobaria (reduced
      atmospheric pressure), particularly among those in the advanced life support
      community. Potential for in situ resource utilization, challenges in meeting
      engineering constraints for mass and energy, the prospect of using lightweight
      plant growth structures on Mars, and the minimal literature on plant responses to
      low pressure all suggest much needed research in this area. However, the limited
      literature on hypobaria combined with previous findings on plant responses to
      atmospheric composition and established principles of mass transfer of gases
      suggest that some plants will be capable of tolerating and growing at pressures
      below 20 kPa; and for other species, perhaps as low as 5-10 kPa. In addition,
      normal and perhaps enhanced growth of many plants will likely occur at reduced
      partial pressures of oxygen (e.g., 5 kPa). Growth of plants at such low and
      partial pressures indicates the feasibility of cultivating plants in lightweight,
      transparent "greenhouses" on the surface of Mars or in other extraterrestrial or
      extreme environment locations. There are numerous, accessible terrestrial analogs
      for moderately low pressure ranges, but not for very low and extremely low
      atmospheric pressures. Research pertaining to very low pressures has been
      historically restricted to the use of vacuum chambers. Future research prospects,
      approaches, and priorities for plant growth experiments at low pressure are
      considered and discussed as they apply to prospects for Martian agriculture.

PMID- 11987304
TI  - Special issue from the workshop "Ecosynthesis: Creating Open and Closed
      Ecosystems on Mars".

PMID- 11987305
TI  - People challenges in biospheric systems for long-term habitation in remote areas,
      space stations, moon, and Mars expeditions.
AB  - People who participate in remote and difficult expeditions, such as the 2-year
      (1991-1993) Biosphere 2 experiment or a future biospheric system on Mars or other
      long voyages, will face individual psycho-physiological, social, and cultural
      value challenges. The individual psycho-physiological vectors include the lure of
      being a hero/heroine and pushing it to the maximum, concealment of problems with
      the belief that he/she can overcome the obstacle alone, as well as the difficulty
      of keeping intact the critical differentiation of the risks associated with the
      overall expedition as opposed to the experimental objectives. The social
      challenges occur as a group dynamic context as well as for the individual,
      resulting in regressions and the need to "act out" one's difficulties. Cultural
      areas of importance that must be taken into consideration will include esthetic,
      ethical, cosmological, and epistemological values. The epistemological values
      must involve the five methods of scientific inquiry for a comprehensive total
      systems project to succeed fully.

PMID- 11987306
TI  - Human factor observations of the Biosphere 2, 1991-1993, closed life support
      human experiment and its application to a long-term manned mission to Mars.
AB  - Human factors are a key component to the success of long-term space missions such
      as those necessitated by the human exploration of Mars and the development of
      bioregenerative and eventually self-sufficient life support systems for permanent
      space outposts. Observations by participants living inside the 1991-1993
      Biosphere 2 closed system experiment provide the following insights. (1) Crew
      members should be involved in the design and construction of their life support
      systems to gain maximum knowledge about the systems. (2) Individuals living in
      closed life support systems should expect a process of physiological and
      psychological adaptation to their new environment. (3) Far from simply being a
      workplace, the participants in such extended missions will discover the
      importance of creating a cohesive and satisfying life style. (4) The crew will be
      dependent on the use of varied crops to create satisfying cuisine, a social life
      with sufficient outlets of expression such as art and music, and to have down
      time from purely task-driven work. (5) The success of the Biosphere 2 first 2
      year mission suggests that crews with high cultural diversity, high commitment to
      task, and work democracy principles for individual responsibility may increase
      the probability of both mission success and personal satisfaction. (6) Remaining
      challenges are many, including the need for far more comprehensive real-time
      modeling and information systems (a "cybersphere") operating to provide real-time
      data necessary for decision-making in a complex life support system. (7) And, the
      aim will be to create a noosphere, or sphere of intelligence, where the people
      and their living systems are in sustainable balance.

PMID- 11987307
TI  - Remote sensing of gene expression in Planta: transgenic plants as monitors of
      exogenous stress perception in extraterrestrial environments.
AB  - Transgenic arabidopsis plants containing the alcohol dehydrogenase (Adh) gene
      promoter fused to the green fluorescent protein (GFP) reporter gene were
      developed as biological sensors for monitoring physiological responses to unique
      environments. Plants were monitored in vivo during exposure to hypoxia, high
      salt, cold, and abcissic acid in experiments designed to characterize the utility
      and responses of the Adh/GFP biosensors. Plants in the presence of environmental
      stimuli that induced the Adh promoter responded by expressing GFP, which in turn
      generated a detectable fluorescent signal. The GFP signal degraded when the
      inducing stimulus was removed. Digital imaging of the Adh/GFP plants exposed to
      each of the exogenous stresses demonstrated that the stress-induced gene
      expression could be followed in real time. The experimental results established
      the feasibility of using a digital monitoring system for collecting gene
      expression data in real time from Transgenic Arabidopsis Gene Expression System
      (TAGES) biosensor plants during space exploration experiments.

PMID- 11987308
TI  - Plant adaptation to low atmospheric pressures: potential molecular responses.
AB  - There is an increasing realization that it may be impossible to attain Earth
      normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply
      because the construction materials do not exist to meet the extraordinary
      constraints imposed by balancing high engineering requirements against high lift
      costs. This equation essentially dictates that NASA have in place the capability
      to grow plants at reduced atmospheric pressure. Yet current understanding of
      plant growth at low pressures is limited to just a few experiments and relatively
      rudimentary assessments of plant vigor and growth. The tools now exist, however,
      to make rapid progress toward understanding the fundamental nature of plant
      responses and adaptations to low pressures, and to develop strategies for
      mitigating detrimental effects by engineering the growth conditions or by
      engineering the plants themselves. The genomes of rice and the model plant
      Arabidopsis thaliana have recently been sequenced in their entirety, and public
      sector and commercial DNA chips are becoming available such that thousands of
      genes can be assayed at once. A fundamental understanding of plant responses and
      adaptation to low pressures can now be approached and translated into procedures
      and engineering considerations to enhance plant growth at low atmospheric
      pressures. In anticipation of such studies, we present here the background
      arguments supporting these contentions, as well as informed speculation about the
      kinds of molecular physiological responses that might be expected of plants in
      low-pressure environments.

PMID- 11987309
TI  - Meningococcal vaccine against serogroups A, C, Y and W-135: new preparation.
      Encouraging immunogenicity studies.
AB  - (1) Prevention of meningococcal meningitis is based on vaccination, and
      chemoprophylaxis in case contacts. The five main meningococcal serogroups known
      to be pathogenic for humans are A, B, C, Y and W-135. Their geographic
      distribution is variable. In France, two-thirds of cases are due to serogroup B,
      which is poorly immunogenic and for which there is no vaccine; the only licensed
      vaccine offers protection solely against serogroups A and C. (2) A meningococcal
      polysaccharide vaccine directed against serogroups A, C, Y and W-135 has been
      granted temporary authorization for use by pilgrims to Mecca and for case
      contacts. (3) The vaccine elicits antibodies against the four serogroups in most
      adults, at least in the short term. It is poorly immunogenic in children under
      two years of age, especially against serogroup C. (4) The preventive efficacy of
      the vaccine against meningitis due to serogroups Y and W-135 is not known, and
      few data are available on serogroups A and C. Protection has not been shown
      beyond two years after vaccination. At one year the vaccine provides about 95%
      protection against serogroup A and 65% against serogroup C. (5) Systemic and
      local reactions to vaccination with the four-valent vaccine appear to be
      acceptable. (6) In practice, for want of anything better, the four valent vaccine
      (A, C, Y and W-135) is better than the two-valent vaccine (A+C) for protecting
      pilgrims to Mecca and contacts of patients with serogroup A, C, Y or W-135
      meningococcal infection.

PMID- 11987310
TI  - Epoetin alfa and epoetin beta: new indication. Treatment of anaemia due to
      cytotoxic chemotherapy.
AB  - (1) The standard treatment for symptomatic anaemia due to cytotoxic chemotherapy
      is blood transfusion. (2) The licensing terms for epoetin alfa have been extended
      to cover the treatment of anaemia induced by all cytotoxic drugs, no longer only
      by platinum salts. The licensing terms for epoetin beta have been extended to
      cover some haematological malignancies. (3) The clinical file on epoetin alfa
      contains data from 8 placebo-controlled double-blind trials in patients with
      anaemia. Four trials showed a significant reduction (of 12-35%) in the number of
      patients transfused during the second and third months of treatment with epoetin
      alfa. (4) Quality of life was mentioned in only two trial reports. In one, the
      score was significantly better on epoetin alfa than on placebo, but the practical
      repercussions of this difference are unclear. In the other trial there was no
      significant difference between the groups. (5) The clinical file on epoetin beta
      contains data only from unblended dose-finding studies showing a favourable
      impact on the haemoglobin level and transfusion requirements. (6) The preventive
      effect of the two epoetins has not been compared with that of alternative
      treatments. (7) The main known risks of epoetin are arterial hypertension and
      thrombosis. Stimulation of tumour growth cannot be ruled out. (8) Epoetin beta
      has a practical advantage, in that it can be stored for a few days at room
      temperature. (9) In practice, epoetin is the standard treatment of anaemia after
      chemotherapy, outside emergency situations.

PMID- 11987311
TI  - Capecitabine and tegafur + uracil: new preparations. Metastatic colorectal
      cancer: two oral fluorouracil precursors, few advantages.
AB  - (1) The standard chemotherapy for metastatic colorectal cancer is intravenous
      fluorouracil combined with calcium folinate. This treatment improves the median
      survival time by approximately 4-6 months compared with optimal palliative care.
      (2) Two metabolic precursors of fluorouracil are now available in the European
      Union for first-line oral treatment of metastatic colorectal cancer, namely
      capecitabine and tegafur + uracil. According to the licensing terms, only the
      tegafur-uracil combination must be given with calcium folinate. (3) The
      evaluation files on each of these two cytotoxic agents contain data from two
      comparative unblinded trials versus intravenous fluorouracil + calcium folinate
      (Mayo Clinic protocol). None of these trials showed a difference in survival. (4)
      Both drugs caused severe diarrhoea in 12% of patients. Severe palmoplantar
      erythrodysesthesia was more frequent on capecitabine. Longer postmarketing follow
      up is available for the tegafur + uracil combination, which has been used in
      Japan for many years. (5) Patients receiving capecitabine or tegafur + uracil +
      calcium folinate have to take large numbers of tablets or capsules. (6) In
      practice, the standard treatment for metastatic colorectal cancer remains the
      fluorouracil + calcium folinate combination. The tegafur + uracil + calcium
      folinate combination is only useful for patients who prefer oral administration.
      Capecitabine has no documented advantage over this latter combination.

PMID- 11987312
TI  - Gabapentin: new indication. Little impact on partial epilepsy in children between
      3 and 12.
AB  - (1) The standard treatment for partial epilepsy in children is carbamazepine. The
      efficacy of other antiepileptics has also been documented, either alone
      (phenobarbital, oxcarbazepine, valproate sodium, phenytoin), or in drug
      combinations (lamotrigine, topiramate). (2) A licence extension has been granted
      in France for gabapentin in partial epilepsy in children aged 3 to 12 years, in
      combination with other antiepileptics. (3) The clinical file contains no data
      from trials comparing gabapentin with other antiepileptics. (4) The main double
      blind trial involved 247 children who were treated either with their usual
      treatment + gabapentin or usual treatment + placebo. Gabapentin was only
      moderately effective, and the overall number of responders did not differ
      significantly between the gabapentin and placebo groups. (5) In this trial the
      main adverse effects among the children on their usual treatment + gabapentin
      were behavioural disorders (hostility and mood swings). (6) In practice, the
      licensing of gabapentin for children with partial epilepsy aged between 3 and 12
      years changes nothing in their practical management.

PMID- 11987313
TI  - Electrolyte disorders and sodium phosphates.

PMID- 11987314
TI  - Nitrofurantoin and neuropathy.

PMID- 11987315
TI  - Erythroblastopenia with epoetin.

PMID- 11987316
TI  - Convulsions and hypersensitivity reactions linked to bupropion.

PMID- 11987318
TI  - Failure of ceramic femoral heads.

PMID- 11987317
TI  - Urinary retention with loperamide.

PMID- 11987319
TI  - Drugs in 2001: a number of ruses unveiled.

PMID- 11987320
TI  - Type 1 diabetes: benefits of intensive insulin therapy. Patients should control
      blood glucose strictly.
AB  - The DCCT randomised trial compared insulin therapy with strict glycaemic control
      versus less strict insulin therapy in patients with type 1 diabetes. The trial
      itself lasted more than 6 years, and most of the patients were subsequently
      followed up for another 4 years. The initial benefit of strict glycaemic control
      on the onset or worsening of diabetic retinopathy and nephropathy does appear to
      persist in the long term

PMID- 11987321
TI  - Chimerism of the transplanted heart.

PMID- 11987322
TI  - Chimerism of the transplanted heart.

PMID- 11987323
TI  - Prevention of relapse in schizophrenia.

PMID- 11987324
TI  - Prevention of relapse in schizophrenia.

PMID- 11987325
TI  - Hereditary periodic fever.

PMID- 11987326
TI  - Hereditary periodic fever.

PMID- 11987327
TI  - Head and neck cancer.

PMID- 11987328
TI  - SchoolAsthmaAllergy.com and World Allergy Awareness Day.

PMID- 11987329
TI  - Shots and school nurses: six significant questions.

PMID- 11987331
TI  - What would you do?

PMID- 11987332
TI  - Collaboration: higher education in the school setting.

PMID- 11987333
TI  - Meet Jacquelyn Sowers. Interview by Deb Ilardi.

PMID- 11987334
TI  - Child health insurance update ... a message from president-elect, Linda Wolfe.

PMID- 11987336
TI  - Tips for discussing the symptoms of ADHD with children.

PMID- 11987337
TI  - Now and future primary care.

PMID- 11987338
TI  - Strategizing your career.

PMID- 11987339
TI  - Conquering stress.

PMID- 11987340
TI  - Re-energizing hospital care. On the heels of Florence Nightingale.

PMID- 11987341
TI  - Nigeria unnoticed. Never stop networking.

PMID- 11987342
TI  - Carrying your own lamp. Japanese theory and practice.

PMID- 11987343
TI  - "Learning & leading globally" 1999-2001 presidential call to action.

PMID- 11987345
TI  - Creating a career, realizing a dream.

PMID- 11987347
TI  - Advanced practice nursing care extends life spans for elderly cancer patients.

PMID- 11987346
TI  - Starved for attention.

PMID- 11987348
TI  - Swinging soothes elderly patients with dementia.

PMID- 11987349
TI  - ANA project seeks to increase nurses input in federal policy.

PMID- 11987350
TI  - Life reviews: helping Alzheimer's patients reclaim a fading past.

PMID- 11987351
TI  - I remember that! Building memory confidence in the elderly.

PMID- 11987352
TI  - Preventing falls in the elderly.

PMID- 11987353
TI  - Ethnicity and end-of-life decision-making.

PMID- 11987354
TI  - The family vs. the government: the changing face of geriatric care in South
      Korea.

PMID- 11987355
TI  - Aging nurses in an aging society: long-term implications.

PMID- 11987356
TI  - Suicide in the elderly.

PMID- 11987357
TI  - Substitute school nursing: an orientation session.

PMID- 11987359
TI  - Physical education statement by the President's Council on Physical Fitness and
      Sports.

PMID- 11987361
TI  - Covering Michigan's kids.

PMID- 11987362
TI  - Thoughts for the profession.

PMID- 11987363
TI  - What strategies should MNA use to address nurses' problems in the work setting?

PMID- 11987364
TI  - U.S. Department of Health and Human Services: Office of Disease Prevention and
      Health Promotion--Healthy People 2010.

PMID- 11987365
TI  - Needlestick protection, tightened shift language highlight new Marquette
      contract.

PMID- 11987366
TI  - Bay area gains improved staffing language, better benefits.

PMID- 11987367
TI  - Saying no to mandatory overtime.

PMID- 11987368
TI  - Needlestick: not out of the woods yet.

PMID- 11987369
TI  - Protecting yourself from infection.

PMID- 11987370
TI  - Just like her mother.

PMID- 11987371
TI  - Disparity versus diversity. Meeting the challenge of Europe's underserved
      populations.

PMID- 11987372
TI  - Universal access to health care: if not now, when?

PMID- 11987373
TI  - When urban U.S. means urban underserved.

PMID- 11987374
TI  - People in crisis: vignettes from the Victorian Order of Nurses.

PMID- 11987375
TI  - Respecting tradition in healing.

PMID- 11987376
TI  - Kangaroo care: not just for stable preemies anymore.

PMID- 11987377
TI  - Touching calms premature infants.

PMID- 11987378
TI  - Behavior problems in children with epilepsy.

PMID- 11987379
TI  - Positive situational focusing: Pollyanna or a powerful stress prevention
      strategy?

PMID- 11987380
TI  - Envisioning new nursing roles and scopes of practice.

PMID- 11987381
TI  - Serving the underserved. An international imperative.

PMID- 11987382
TI  - The language of pain.
AB  - In a well-known advertising campaign, respondents asked to spell "relief"
      invariably spelled the name of a popular antacid. Three decades ago, an American
      nurse working in Sweden found less unanimity, however, when it came to the
      spelling of "pain." Intrigued by the clear distinction that her patients made
      between pain and ache, Fannie Gaston-Johansson wanted to know more. Did the same
      differentiation transcend cultural and linguistic divides? Was it possible to
      develop a simple, word-based tool to reliably quantify pain? Her search for these
      and other answers would result in outstanding scholarship, a patented invention
      and history-making achievement.

PMID- 11987383
TI  - Linking hands online: the Korean connection.

PMID- 11987384
TI  - Linking hands online: the Scandinavian connection.

PMID- 11987385
TI  - Direct to consumer.

PMID- 11987386
TI  - Taking it to the BANK. Building an Information Architecture of Nursing Knowledge.

PMID- 11987387
TI  - From black bags to interactive work stations.

PMID- 11987388
TI  - Conquering dysfunctional anxiety: what you say to yourself matters!

PMID- 11987389
TI  - Outdoor healing spaces: a personal and professional journey.

PMID- 11987390
TI  - [Ecosystem health and environmental management].
AB  - Ecosystem health is very relational to environmental management. Ecosystem health
      is the aim of environmental management. Ecosystem health provides new thoughts
      and new methods to environmental management. Healthy ecosystem is a fundamental
      basis to realize regional sustainable development. The succession process of
      ecosystem health is the preparation to optimize environmental management. At the
      same time, optimized environmental management provides macro decision-making and
      social and economic ensurance for ecosystem health. From the view of subject
      development, this paper deals with the background, theoretical fundament and
      application process of ecosystem health and also deals with the relationship
      between ecosystem health assessment and environmental management. The paper puts
      forward the aim of environmental management: healthy ecosystem-->healthy
      environment-->healthy foods-->healthy human ecosystem-->healthy social
      development.

PMID- 11987391
TI  - [Eco-toxicological effects of heavy metals on the inhibition of seed germination
      and root elongation of Chinese cabbages in soils].
AB  - The Eco-toxicity effects of individual Cu, Zn, Pb and Cd on the inhibition of
      seed germination and root elongation of Chinese cabbages (Brassica pekimensis)
      were tested in four types of soils (red loam soils, meadow brown soils, chestnut
      soils and dark brown soils) and water solution. The combined effects of heavy
      metals pollution were determined with meadow brown soils. Results indicated that
      with same concentration, the inhibition rates of heavy metals on root elongation
      of Chinese cabbages are stronger than that on the seed germination. The
      inhibition effects of heavy metals on the root elongation of Chinese cabbages in
      soils are much lower than that in water, indicating that soils play an important
      role of buffering on heavy metals pollution. Inhibition rates of heavy metals on
      the root elongation (IRHMRE) of Chinese cabbages are significantly negative
      related with the contents of organic matter (OR) and Kjedahl-nitrogen (K-N) in
      soils, however, there is no significant related between IRHMRE and soil pH, so
      does the content of T-K. In the concentrations that result in the irritated
      effect in the single form of Cu, Zn, Pb and Cd pollution, synergic effects are
      produced significantly when four heavy metals are combined. As the results, the
      threshold values that result in the inhibition effects on root elongation in
      Chinese cabbages decrease markedly.

PMID- 11987392
TI  - [Outflows of trihalomethane precursors from soils].
AB  - Outflows of trihalomethane formation potential (THMFPs) which was chosen as an
      index of the amount and reactivity with chlorine of THMs precursors from soils
      were studied with soil column experiment. The results indicated that factors
      influencing THMFP concentrations of leacheates were the physicochemical
      properties of soils, especially contents, composition and reactivities with
      chlorine of humic substances, the pH value of feed solution and cumulative
      leaching volume. The THMFP concentrations of leachates rose with increases in
      amounts of humic substances with high solubility as well as reactivity with
      chlorine. The effluents of soil samples contained the lowest THMFP concentrations
      under the feed solution of the lowest pH value (pH 3.0). THMFPs appeared to more
      easily flow out from soils with the feed solution of lower pH value, which was
      properly due to the increases in solubility of humic substances under the lower
      pH value conditions. In most cases, THMFP concentrations of leachates showed
      decline with the increase of cumulative leaching volumes of feed solution.

PMID- 11987393
TI  - [Concentrations of aerosol and related gases in Beijing].
AB  - The measurement was made in 3 periods from May to September of 2000 in Beijing.
      The measurement species included SO4(2-), NO3-, NO2-, Cl- of aerosol and related
      gases. The hourly variation of the concentration was presented. It showed that
      NO3-, NO2-, Cl- of aerosol and HCl, HNO2, HNO3 of gas varied with regularity. The
      variation of gas SO2 and aerosol SO4(2-) depended on the emission of SO2. The
      peak time of SO4(2-) was about 2 hours later than SO2.

PMID- 11987394
TI  - [Combustion characteristics of mixed municipal solid waste in thermogravimetric
      analysis and lab scale fluidized bed].
AB  - In this paper, thermogravimetric analysis (TGA) and a lab scale fluidized bed
      facility were used as experimental means. The data in the two different
      experimental systems were introduced and compared. Experimental results show that
      the differences of combustion velocity among different wastes in Fluidized
      Bed(FB) were very small whereas in thermogravimetric analyzer the differences can
      not be ignored as the value range of combustion velocity variation was between
      0.49 and 5.5. It took municipal solid waste 3-3.5 min to burn out in FB, but in
      thermogravimetric analyzer, the time was 20-25 min. It can be concluded that, in
      general, the behavior of a mixture of waste in TGA can be expressed by simple
      combination of individual components of the waste mixtures. Only minor deviations
      from the rule were observed. In FB, it was found that, for some mixtures, there
      was interference among the components during FB combustion.

PMID- 11987395
TI  - [Comparison of ISE, ASV and FQ for complexation characterization of river water
      DOC with copper].
AB  - Condition stabilization constants of complexation between naturally occurring
      organic ligand in river water and copper were measured lgk and compared by using
      ISE, ASV and FQ methods. The measured lgk results were 2.29-6.47 by ISE, 2.61
      6.91 by ASV, and 3.52-4.71 by FQ, respectively. The constants went up with the
      raise of pH, the decrease of copper content, and the increase of ligand
      concentration.

PMID- 11987396
TI  - [Lead emission amount from coal combustion and its environment effect in Xi'an
      City].
AB  - For study the lead emission amount from coal combustion and its environment
      effect, the lead content of coal, ash and cinder of power station and coal-fired
      boiler, the lead content of dusts in the period of heating time and the non
      heating time in Xi'an City were studied in this paper. The results show that
      amount of lead emission from 1 ton coal combustion, which lead content in coal
      was 30 g, was 20 g in atmosphere. The rate of lead emission of coal combustion
      was about 66%. About 10 million tons of coal was straight burning every year in
      Xi'an City and suburb, those coal mainly come from Permo-Carboniferous coal in
      Weibei coal mine, Shaanxi, their average lead content was 30 mg/kg. So the total
      lead emission from coal combustion to atmosphere was about 200 t annually in
      Xi'an City.

PMID- 11987397
TI  - [The concentration and source of atrazine residue in water of Guanting
      reservoir].
AB  - The atrazine in water was determined by SPE-LC-MS. It only took 40 min to
      analysis a sample. The detection limit was 10 ng/L. Atrazine was detected in
      water of Guanting reservoir. The concentration of atrazine in water samples of
      Guanting reservoir was 0.67-3.9 micrograms/L. The source of atrazine in water was
      discussed. A plant situated at upstream of Yanghe River was thought a primary
      source of atrazine in Guanting reservoir.

PMID- 11987398
TI  - [Mapping sensitivity of surface waters to acidification in China].
AB  - Acidification of surface waters can be decided by some environmental factors,
      such as soil's buffering capacity, neutralization capacity of bedrock to acid
      deposition and types of land use, among which the most important factor is the
      soil's resistance to acidification. Therefore, information about soils, geology
      and land use can be used to predict the regional occurrence of acidification
      surface waters under different flows. In this paper, information and data about
      Chinese soils, geology and land use types were collected to determine and to map
      the sensitivity of surface waters to acidification. Results showed that in China,
      most surface waters were not sensitive to acidification. The few most sensitive
      surface waters were located in the north part of Northeastern China, accounting
      for 2.67% of all the country land. It was the combined results of strongly
      acidified ortho podzolic soil, acidified bedrock and coniferous forest. Surface
      waters which were not very sensitive to acidification were distributed both in
      the region of dark brown forest soil in Northeastern China and in the ferralsol
      and yellow-brown earth area in Southern China, occupying 15.2% of all the country
      land. The other surface waters which distributed on 82.11% of all the country
      land were not sensitive to acidification at all. Most in the Northern China
      because of the high resistance of soils to acidification and the others were in
      the Southern China where calcareous soils and agricultural lands were widely
      distributed. Since soils were quite resistant to acid, acidification of surface
      waters of large area will not likely occur in the southern region of China
      suffering from heavy acid deposition in the near future. Nevertheless, the acid
      deposition in Northern China should be controlled as soon as possible in case
      that acidified surface waters will be found there.

PMID- 11987399
TI  - [The release amount and its change law of CO2 from soils in Xi'an area].
AB  - On the basis of the principle of which CO2 is absorbed by the solution of NaOH,
      the release amount of CO2 in soils under different vegetation was observed round
      the clock. The material shows that the release amount of CO2 from soils in Xi'an
      area changed clearly in 24 hours in months. The release amount changed from low
      to high and then to low from the morning to the next morning. The change of the
      release amount of CO2 was same that as the temperature, but the change of the
      former was about 4-6 hours later than that of the latter. The temperature was
      main factor determining change law of release amount of CO2 from soils and its
      rising and falling bring out the increase and decrease of release amount of CO2.
      The release amount of CO2 from soils was changing along with different
      vegetation. The forestry land was greater than grassland and the grassland was
      greater than the bare land in the release amount. The release amount was greater
      in day than in night.

PMID- 11987400
TI  - [The role of additives in bio-mass coal briquette on sulfur retention
      enhancement].
AB  - The research first conducted the sulfur-fixing experiment of bio-mass coal
      briquette in a tubular furnace. The impacts of three additives Al2O3, Fe2O3 and
      MnO2 on the sulfur retention by calcium-based sorbent in briquette were
      investigated, and only Al2O3 displayed the enhancement of sulfur retention. The
      TGA experiment was further carried out, and proved that the high-temperature
      decomposition of CaSO4 in the deoxidization atmosphere was effectively inhibited
      with the addition of Al2O3. The XPS and XRD analyses of briquette ash showed that
      due to the interaction among Al2O3, CaSO4 and CaO, the composite
      CaSO4.3CaO.3Al2O3 which has more thermal stability was formed. With its wrapping
      or binding onto the surface of CaSO4 crystal, the decomposition of CaSO4 was
      mitigated.

PMID- 11987401
TI  - [Physicochemical characterization of the PM10 in ambient air of northwestern
      Beijing urban area during heating-period].
AB  - Based on monitoring data, the daily and day-to-day changes of PM10 mass
      concentrations in northwestern Beijing urban area during heating-period were
      discussed. XRD and SEM were applied to study the mineral compositions and
      morphology of the PM10, respectively. It was concluded that concentration of PM10
      at nighttime was higher than that at daytime generally. By XRD analysis, it was
      found that the finer the particles, the less the minerals in it. Furthermore,
      from the SEM micrograph, five types of the particles, mostly from coal burning
      and diesel exhaust in number concentration, were classified as chain-like
      aggregate, cluster aggregate, spherical particle, flake-like particle and non
      regular particle.

PMID- 11987402
TI  - [Experiment of wet FGD process with waste marble].
AB  - The wet FGD process with waste marble was studied experimentally, and the mass
      transfer reaction mechanism was analyzed. Main parameters including liquid/gas
      ratio, pH value of the absorbent slurry and inlet SO2 concentration, etc.
      affecting SO2 removal efficiency were studied for the process. The results show
      that the suitable operating conditions were recommended as follows: pH0 = 5.5
      6.5, L/G = 3L/m3, a = 2%; the sulfur dioxide removal efficiency can reach more
      than 60% when the inlet SO2 concentration was 1000 ml/m3. In addition, the
      industrial application potential for this process was discussed.

PMID- 11987403
TI  - [Characters of fuzzy control parameters pH and ORP of denitrification in SBR
      process].
AB  - In order to achieve fuzzy control of denitrification in Sequencing Batch Reactor,
      the effects of beer wastewater, sodium acetate, methanol and endogenous carbon
      source on the relationships between pH, ORP and denitrification were studied.
      Different amount of beer wastewater and two different methods of dose were
      examined. All the results indicated that ORP decreased quickly and then slowly,
      when denitrification stopped ORP decreased quickly, showing a breakpoint on the
      ORP curve; pH increased till denitrification stopped, then decreased, showing a
      turning point. When carbon was the limiting factor, through comparing the
      increasing rate of pH, whether the carbon was enough or not could be known and
      when the carbon should be added again could be decided.

PMID- 11987404
TI  - [Adsorption properties of dye compounds on the sediments in Qinghe].
AB  - The adsorption properties of six kinds of dyes compounds on the sediments in
      Qinghe were studied through batch technique. The influences of pH, ion strength
      and temperature on adsorption as well as the adsorption isotherms were discussed
      and determined. It was shown that pH value and ion strength were the main effect
      factors on the adsorption, and the adsorption percentage increased with the
      temperature increase. The adsorption of these dye compounds on the sediment
      exhibited Freundlich adsorption behavior. The dynamic adsorption indicated that
      the adsorption process was divided into two steps: fast adsorption (less than 1
      hours) and slow adsorption (more than 12 hours).

PMID- 11987405
TI  - [Stability of the two-stage SBR system treating dyeing wastewater during a long
      term operation].
AB  - The stability of the two-stage SBR system treating dyeing wastewater was
      investigated during a 120-cycle continuous operation. The system was fed with
      influent of low dye concentration and high dye concentration. The results showed
      that the two-stage SBR system was adaptable to the change of influent quality and
      operation conditions during the long-term operation. It could efficiently remove
      the pollutants in the wastewater, the average dyestuff and COD removal rates were
      81% to 92.5% and 89.4% to 93.1% respectively for low and high influent loading,
      and could produce continuous good quality effluent. In the two-stage SBR system,
      the anaerobic sludge had the characteristics of high activity and strong
      pollutant degradation ability, and the aerobic sludge existed in the form of
      aggregate structure, which helped stabilize the effluent quality.

PMID- 11987406
TI  - [The catalytic wet air oxidation reaction of acetic acid with Ti-Ce series
      catalyst].
AB  - The influence factors and reaction mechanism during the catalytic wet air
      oxidation of acetic acid with Ti-Ce series catalyst was investigated in this
      paper. The results show that the reaction was influenced by the catalyst load,
      the reaction temperature, the pH of the reaction system and the partial pressure
      of oxygen. More than 90% removal efficiency of acetic acid (as COD) can be
      obtained at the reaction conditions as follow: temperature 230 degrees C, oxygen
      partial pressure 2-2.5 MPa, catalyst amount 5 g/L, initial pH of the system 3.0
      and reaction time 1 h. With Ion Chromatography, the formic acid formed during the
      reaction process was detected. The formic was found during the wet air oxidation
      of acetic acid in the absence of catalyst, but can not be detected during the
      catalytic wet air oxidation process with Ti-Ce catalyst. It means that the
      presence of catalyst in the system not only improve the removal efficiency, but
      also change the oxidation pathway.

PMID- 11987407
TI  - [Municipal wastewater treatment using the up-biological aerated filter].
AB  - Up Biological Aerated Filter(UBAF) was used for the advanced wastewater
      treatment. The average removal rate of CODCr, BOD5, SS, NH4(+)-N and turbidity
      was 22.2%, 55%, 84.4%, 49%, 75.6% respectively. The hydraulic and COD load of
      influent influenced directly the quality of effluent.

PMID- 11987408
TI  - [Calculating emissions of exhaust particulate matter from motor vehicles with
      PART5 model].
AB  - PART5, a vehicle particulate emission factor model developed by USEPA, was
      modified and then used to obtain the emission factors of exhaust PM10 and PM2.5
      from on-road automobiles, trucks and motorcycles in Beijing. The total exhaust
      PM10 and PM2.5 emissions from motor vehicles in 1995 and 1998 were calculated
      separately. The contribution ratios of different types of vehicles to the total
      vehicular emissions, and the share of different exhaust particulate components
      including Pb, direct SO4(2-), soluble organic fraction (SOF) and remaining carbon
      portion (RCP), were also estimated. It was shown that the emission factors of
      exhaust PM10 and PM2.5 from gasoline motor vehicles, motorcycles and heavy-duty
      diesel vehicles in Beijing were 1.7-8.6 times, 2.1-3.5 times and 1.3-1.5 times,
      respectively, of the USA average emission levels during the same period. The
      total exhaust PM10 and PM2.5 from vehicles were 2445 tons and 1890 tons in 1995
      in Beijing, and increased to 3359 tons and 2694 tons in 1998, which increase by
      37.4% and 42.5%, respectively.

PMID- 11987409
TI  - [Production of chitosan used for flocculant in medium scale].
AB  - After the preparing chitosan in laboratory scale, the production of chitosan used
      for flocculant in medium scale was carried out. The optimum processes for
      producing chitosan in the three steps of reaction including removal calcium,
      removal protein and deacetylation were obtained. Comparing with the other methods
      for producing chitosan, the cost of this method cut down 22%, the production
      period shortened 66%, and the main properties were closed to or exceeded the
      commercial chitosan products.

PMID- 11987410
TI  - [Tetrabutyl titanate hydrolysis prepared TiO2 photocatalysis loaded with platinum
      technology].
AB  - Photocatalysts Pt/TiO2 coated on hollow glass beads were prepared by tetrabutyl
      titanate hydrolysis with Sodium silicate on hollow glass beads at various
      condition and loaded with platinum varying from 0.2% to 2.4% by weight. Sodium
      pentachlorophenolate (PCP-Na) solution were used to examined for their
      photoactivity and characterized by X-ray and BET. The results indicated that the
      optimization condition to prepare photocatalysts: Water to titanium alkoxides was
      100, Sintering temperature was 650 degrees C, Diameter of hollow glass beads was
      0.5 mm, TiO2: sodium silicate: hollow glass beads was 10:2.5:20, Platinum content
      of photocatalysts was about 1.4%-1.6%. When the experiments were carried out in
      such conditions, the initial concentration of PCP-Na was 100 mg/L, initial pH was
      6.5, oxygen flux was 1.6 mL/s, illumination intensity was 30 kW.m-2, catalysts
      was 2 g/L, illumination time was 2 hours, respectively. Then the rates removals
      of PCP-Na could reach 92.0%.

PMID- 11987411
TI  - [Biodegradation of lignin in wheat straw by alkaliphilic ligninolytic bacteria
      with compounded carbons].
AB  - The article researched enzymes production, the degradation rate of lignin and
      strain growth of alkaliphilic ligninolytic bacteria strain No. 6 in alkaline
      liquid medium (pH approximately 10.5) with compounded carbons. The results showed
      that the highest activities of laccase and MnP were 2915.37 U/L (4th d) and
      1152.88 U/L (8th d), respectively, and the strain degraded 49.84% lignin of wheat
      straw during ten days cultivation. The changes of ultrastructure of wheat straw
      caused by strain No. 6 attack were investigated with SEM (scan electron
      microscopy).

PMID- 11987412
TI  - [Water quality evaluation of the Three Gorges Reservoir area].
AB  - One year water quality monitoring results of 16 sections alongside the Three
      Gorges Reservoir area were presented. From the evaluation carried out using the
      integrated polluted index (P value), some characteristics of the water quality
      were obtained. The results showed that water quality of the Three Gorges
      Reservoir area was slightly polluted in 1999 mainly because of the discharge of
      urban sewerage and industrial wastewater. Main polluted city sections were along
      the river banks of Chongqing, Changshou, Fuling and Wanzhou. Evaluation also
      showed that there were 4 indicators that, to different extent, affected the water
      quality: colon bacillus, TP, non-ionic ammonia and oils.

PMID- 11987413
TI  - [Annual cycle and budgets of nutrients in the Bohai Sea].
AB  - High concentrations of dissolved inorganic nitrogen and phosphate contributed
      much to the environmental problems in the Bohai Sea in the last decade. It is
      important to understand the cycle and the budget of nutrients for the
      environmental management. A three-dimensional ecosystem model, coupled with a
      physical transport model, was adopted in this study. The simulation of the year
      1982 was validated by data in 1982/1983. There were depletion from spring to
      summer and elevation from autumn to winter for nutrients. The higher
      concentration of phosphate was found at the Bohai Bay and the concentration of
      phosphate maintained higher level in the whole year. The higher concentration of
      dissolved inorganic nitrogen located near the Huanghe Estuary. Production and
      respiration were the most important sink and source of nutrients. The
      remineralization of the detritus pool can compensate 30 percent of the
      consumption of nutrient by the production process. The inputs of phosphates and
      nitrogen from river were P 0.55 x 10(3) t and N 52.7 x 10(3) t.

PMID- 11987414
TI  - [Mass transfer model of membrane extraction for recovery of cadmium ion and zinc
      ion].
AB  - By measuring the residence time distribution (RTD) curve of shell side and tube
      side of hollow fiber modules, it was found that the flow status in hollow fiber
      module with moderate or low packing density was complicated. For tube side, there
      were deviation between the experimental RTD curves and the theoretical laminar
      flow ones, which indicated that the flow status in tube side was between laminar
      flow and turbulent flow. For shell side, the experimental RTD curves agreed well
      with the laminar flow ones. The deviations as low as +/- 5% between the
      experimental average residence times and the theoretical ones suggested that
      there was no apparent non-ideal flow in the hollow fiber module with medium
      packing density. Based on the comparison between the experimental results and
      some typical correlations, a new velocity profile was purposed to describe the
      flow status in hollow fiber modules. According to the results of cadmium
      transport, the individual mass transfer coefficient correlations were developed.
      The zinc outlet concentrations predicted by the new correlations agreed
      relatively well with the experimental results, the relative deviation was among
      +/- 25%.

PMID- 11987415
TI  - [Quantitative analysis of landscape conditions of the desertified sandy grassland
      in Ordos Plateau].
AB  - The landscape condition of the sandy grassland in southeast of Ordos Plateau was
      analyzed based on the data from field investigation along two intercepting 5 km
      transects. Summary on frequency of the patches showed that small-scale patches
      were prominent in this area, with 95% of total patches smaller than 50 m and
      average dimension of patches 15 m, while there were also a couple of large-scale
      mobile sandy patches. Environmental heterogeneity dependent on spatial scales was
      revealed by semivarogram in the sampling area. The large fractal dimensions of
      percent coverage of bare ground, close to 2, indicated dominant small-scale
      spatial variance. This result implies a relative stabilized landscape and also a
      desertified area.

PMID- 11987416
TI  - [Vapor extraction technology in oil contaminated soil remediation].
AB  - In order to study the Vapor Extraction Technology that can be applied to China,
      on the basis of mechanism analysis of Vapor Extraction Technology for oil
      contaminated soil, a simplified and practical contaminant removal model to
      simulate the soil remediation time was presented. With the typical unsaturated
      soils in North of China, the effects of the vapor flow rate, soil water content
      and quality on the remediation process were studied. The results showed that the
      best value of flow velocity was existed, and water content had different
      influence on different kinds of soil, for silty soil, the efficiency of
      remediation enhanced with water content increase, but there was a reverse result
      for clayey soil. Through one-dimension soil column experiments, the results
      showed that these factors had different effects on remediation time. The research
      using the soil column apparatus show that the predicted results were validated
      and the applied conditions of this model were qualified.

PMID- 11987417
TI  - [Effects of soil pH value on the bioavailability and fractionation of rare earth
      elements in wheat seedling (Triticum aestivum L.)].
AB  - The effect of soil pH value on the bioavailability and fractionation of rare
      earth elements (REEs) in wheat seedling (Triticum aestivum L.) were investigated.
      The results showed that the concentration of REEs in wheat decreased with
      increasing pH value, and their inter-relationship was best expressed as quadratic
      equation, with correlation coefficients from 0.6003 to 0.9572. The response of
      individual elements to pH value change tended to be Ce > La > Nd > Sm > Gd > Yb >
      Eu, with Ce most sensitive to changing pH conditions and Eu lest. Chemical
      fractionation indicated that the order of REEs concentration in three fractions
      could be as follows: B2(NH2OH.HCl extraction) > B3(H2O2-NH4Ac extract) > B1(HAc
      extract). The increase of pH value resulted in transformation from B1 to B2 and
      B3. Multiple regression analysis was utilized to obtain the regression equations
      for prediction plant uptake of REEs. B1 fraction was most available to wheat.
      Meanwhile, it was found that the fractionation factors of REEs in wheat were
      negatively correlated with the soil pH value.

PMID- 11987418
TI  - [Dynamics of the human respiratory system parameters at different rates of +Gz
      load rise].
AB  - Studies of the dynamics of human respiratory system parameters during 15-s runs
      with +Gz loads from 6 to 9 units and rates of rise equal to 1, 2, 3 and 5 units/s
      showed that increase in the rate of rise produced specific shifts in the
      breathing cycle structure which characterize the voluntary adaptation of humans
      to g-loads. Results also make it evident that despite absence of difference in
      the respiratory reactions during +Gz runs, in the period following exposure the
      distinct increases in the parameters of external breathing and gas-energy
      exchange correlated with the rate of g-rise. This allows the conclusion that
      because of the reasons discussed in the paper the physiological cost of Gz
      tolerance grows as the rate of g-rise gets high.

PMID- 11987419
TI  - [Dependence of the thoracic abdominal ratio of the respiration parameters on body
      positioning relative to the vector of gravity].
AB  - Abdominal and thoracic functional reserves of respiration and level of their
      involvement in spontaneous breathing were investigated in 10 male volunteers aged
      20 to 22 put in horizontal head-down (-7 degrees and -30 degrees) or orthostatic
      (+70 degrees) position. The thoracic-abdominal functional reserves of respiration
      dependent on the spatial positioning of the body were found to be the factor that
      determines magnitude of contribution of the thorax and diaphragm in the breathing
      volume.

PMID- 11987420
TI  - [Morphological and cytogenetic disorders in rats following chronic exposure to
      elevated radiation].
AB  - Object of the investigation were effects of elevated radiation background on
      specific body systems in two generations of rats that had been chronically
      exposed to radiation in the most badly polluted areas of the Kaluga district and
      eaten local food. Findings included some compensatory deviations in the white
      blood count, decrease in karyocytes and increase in chromosomal aberration rate
      in nucleus-containing cells from the femoral bone marrow in younger animals of
      several groups, morphologic and histochemical shifts in mucous membrane of the
      esophagus and the stomach, and morphofunctional changes in neurons and glia of
      the cerebral cortex. These changes are compensatory-adaptive by nature and
      indicative of destabilization of homeostasis in experimental animals.

PMID- 11987421
TI  - [Electrophysiological and neurochemical analysis of the biological effects of
      disturbances of Earth's magnetic field].
AB  - Geomagnetic effects on quantitative characteristics of alpha-rhythm were assessed
      by shifts in electroencephalograms recorded in 126 essentially healthy human
      subjects and changes in lipid metabolism in the cortex and white matter in 140
      white rats. Indices of the geomagnetic activity were D, H and Z-components. The
      method of "epoch superposition" revealed an inconsistent alpha-rhythm depression
      and flattening out of the interhemispheric functional asymmetry against
      persistently high electrical activity in the right hemisphere, and biochemical
      asymmetry in consequence of different lipid transformation processes. Spotlighted
      were some nonspecific adaptive reactions to changes in the environment and
      stressful agents.

PMID- 11987422
TI  - [Pathological types of breathing during acute hypoxia].
AB  - Different breathing pathologies (apneusis, gasping, Cheyne-Stokes breathing and
      Kussmaul breathing) were observed in anaesthetized rabbits and rats exposed to
      hypoxia at the altitude of 7500-8000 meters. Dominance of the high-voltage slow
      EKG activity (the delta-wave type) suggested deterioration of the brain
      functioning. Registration of impulse activities of the inspiration and expiration
      breathing neurons in medulla oblongata revealed a higher tolerance of the
      inspiration neurons to severe hypoxia which is attributed to the metabolic
      specifics and functional heterogeneity of these neurons. Character of the neuron
      impulsation is indicative of the reflectory effects of hemo- and
      mechanoreceptors, and the direct effects of different humoral substances
      resulting in impairment of the central control of pacemakers and breathing
      pathologies. It appears that various breathing pathologies in altitude chambers
      and mountains are triggered by the hypoxic factor. However, no dependence was
      established either between the initial breathing rhythm (before "ascent") and
      various types of breathing at the "altitude" or these types of breathing and
      magnitude of hypoxia.

PMID- 11987423
TI  - [Correction of physical performance of mice with the derivatives of 3-oxypyridine
      and pyridine].
AB  - Effects of 21 phenyl ethyl-substituted derivatives of 3-oxypyridine (3-OP), 6
      adamantine derivatives of pyridine (PD) and actoprotectors bemithyl and
      bromanthane on physical performance (PP) were evaluated during treadmill testing
      of mice in ordinary conditions and following vibration. It was stated that in
      ordinary conditions PP was improved by eleven 3-OP derivatives and 3 adamantine
      PDs; nine 3-OP derivatives and 3 adamantine PDs had a positive effect following
      vibration. The actoprotective effect of the compounds depends on their chemical
      composition, dose and a background. A phenyl ethyl-substituted 3-OP derivative
      (code CK-132) administered in ordinary conditions and following vibration
      surpassed significantly the other compounds tested or compared with (bemithyl and
      bromanthane) in this experiment with regard to the spectrum of effective doses (5
      100 mg/kg) and the actoprotective activity (PP improved by 32 to 110%). The
      compound (code CK-132) can be further test validated as an actoprotector against
      the impacts of vibration.

PMID- 11987424
TI  - [Longitudinal studies of cosmonauts' health].
AB  - Presented are data of the follow-up (about 30 years maximum) of cosmonauts (n =
      36, main group) and candidates to cosmonauts (n = 65, control) who were also
      subjected to the systematic medical certification over the whole period in the
      corps of cosmonauts. Analysis of the data on morbidity, body mass, physiological
      and biochemical parameters (BP, lipid and carbohydrate metabolism, hemoglobin
      etc.) revealed that for the most part, dynamics of the health parameters and
      morbidity in remote periods after space flight was age-specific.

PMID- 11987425
TI  - [Hemoglobin as a predictor of cardiovascular problems].
AB  - Analyzed were data of longitudinal studies of health and peripheral blood of AF
      pilots and navigators at the age of 20, 25, 30, 35, 40 and 45. The survey of 846
      men 30 years and older was conducted in two 5-yr cycles. In this cohort, 329 had
      diagnosed neurocirculatory dystonia (NCD), vegetovascular dystonia, and class I
      essential hypertension. Sixty nine men were afflicted with myocardium dystrophy
      or cardiosclerosis. The dispersion analysis provided evidence that 15 to 5 years
      prior to establishment of the NCD diagnosis hemoglobin first increases and then
      decreases. The dispersion analysis applied to the data of repeated measurement
      attested to the predictive meaning of the hemoglobin rise and decrease. Results
      support the hypothesis according to which hemoglobin is but a stable individual
      risk factor but reflects pre-clinic developments in organism.

PMID- 11987426
TI  - [The assessment of radiation hazards in the "MIR" and ISS orbits from the data of
      vehicle and personal dosimetric monitoring].
AB  - The paper describes the procedure of estimating total radiation risk to
      crewmembers during lifetime and possible lifetime reduction in consequence of
      participation in the Mir and ISS missions in different periods of the solar
      activity. The procedure includes analysis of data of vehicle and personal
      dosimetry, and calculations of radiation doses in various Mir compartments and
      accumulated by body tissues of cosmonauts. Calculated doses showed good
      consistency with the doses measured with R-16 on board Mir and personal
      dosimeters. To a first approximation, estimation of doses to cosmonauts and
      radiation risk as a result of participation in ISS missions took into account
      similarity of the Mir and ISS basal modules (geometry, dimensions and mass
      values) and was performed with the use of the space station shielding model that
      had been described elsewhere. The model of ISS radiation shielding will be
      updated as data of dosimetry of ISS compartments and phantom studies are
      available.

PMID- 11987427
TI  - [Sorption-frequency probes and biosensors for gas and liquid composition
      monitoring].
AB  - The review deals with the problems of development of analytical equipment based
      on piezoelectric crystals. Consideration is given to the philosophy of
      determining inorganic and organic compounds, biologically active compounds,
      viruses, and bacteria with piezoelectric resonators. Described are methods of
      immobilization of the biological component, immersion-and-drying analysis, and
      sensor-assisted detection in the soluble phase.

PMID- 11987428
TI  - [The evaluation of the error of the thermal pulse technique used to measure
      moisture content of root substrates in space greenhouse].
AB  - Point thermopulse probes were used to monitor moisture level in the root
      substrates during cultivation of higher plants in a space greenhouse.
      Investigated were performance data of the thermopulse moisture probe in
      integration with the space greenhouse. It was shown that within the substrate
      moisture range from 20 up to 100% of the full saturation the technique error does
      not exceed 1.5%. The thermopulse technique bears much promise for metrologic
      monitoring of the root substrate moisture content in space greenhouses no matter
      water and air supply technology.

PMID- 11987429
TI  - [The use of thermoelectric modules (Peltier elements) in the relative humidity
      control of a hyperbaric environment].
AB  - The author considers an option for automatic relative humidity control of a
      hyperbaric environment demonstrated in a pressure chamber for small animals. To
      achieve the purpose, a device has been developed to cool off gas mixture using
      the Peltier effect and then remove condensate. Experiments were performed with
      two different gas mixtures: O2-N2-He at 25.5 x 10(5) Pa and 30 degrees C and air
      at 6.9 x 10(5) Pa and 22 degrees C. The device enabled stabilization of relative
      humidity in the chamber at 30-40% without bio-objects and at 35-46% with bio
      objects (Wistar rats).

PMID- 11987430
TI  - [The role of the rheological parameters of erythrocytes in maintenance of the
      blood flow structure in stressed rats].
AB  - Analyzed were aggregation and deformation parameters of erythrocytes and their
      correlation in rats stressed by immobilization, cold, hunger, and cold combined
      with hunger, and their controls. Under the above experimental conditions, the
      aggregation rate of erythrocytes grows up without any pronounced changes in the
      deformation characteristics. There was a direct positive correlation between the
      aggregation and deformation parameters of erythrocytes under stress. It is
      assumed that this phenomenon represents a universal mechanism of adaptation of
      the blood viscosity regulation in mammals.

PMID- 11987431
TI  - [Effects of the factor of season on the the physiological status of petroleum
      industry workers in the Polar region].
AB  - There were three medical examinations (in March, June and October) of oilers on
      shift days 5-6 in a field medical post in the Polar region. The survey protocol
      included analysis of morning (before breakfast) biochemical and cell indices,
      physiological examination, testing reactions to standard stimuli (color, tone),
      psychological testing, assessment of factual nutrition, analysis of the
      cardiorespiratory function at rest and during physical tests. It was stated that
      recovery of physical performance varied with the seasons. In March, the shift
      workers were significantly less reactive to the color stimulus. At low ambient
      temperature (-38 degrees C) blood content of alpha 1- and alpha 2-globulins went
      up, and there were atypical proteins and considerable amounts of total
      cholesterol, pre-beta-lipoproteins and alpha-lipoproteins in blood.

PMID- 11987432
TI  - Assessing the learning curve effect in health technologies. Lessons from the
      nonclinical literature.
AB  - INTRODUCTION: Many health technologies exhibit some from of learning effect, and
      this represents a barrier to rigorous assessment. It has been shown that the
      statistical methods used are relatively crude. Methods to describe learning
      curves in fields outside medicine, for example, psychology and engineering, may
      be better. METHODS: To systematically search non-health technology assessment
      literature (for example, PsycLit and Econlit databases) to identify novel
      statistical techniques applied to learning curves. RESULTS: The search retrieved
      9,431 abstracts for assessment, of which 18 used a statistical technique for
      analyzing learning effects that had not previously been identified in the
      clinical literature. The newly identified methods were combined with those
      previously used in health technology assessment, and categorized into four groups
      of increasing complexity: a) exploratory data analysis; b) simple data analysis;
      c) complex data analysis; and d) generic methods. All the complex structured data
      techniques for analyzing learning effects were identified in the nonclinical
      literature, and these emphasized the importance of estimating intra- and
      interindividual learning effects. CONCLUSION: A good dividend of more
      sophisticated methods was obtained by searching in nonclinical fields. These
      methods now require formal testing on health technology data sets.

PMID- 11987433
TI  - The influence of methodologic quality on the conclusion of a landmark meta
      analysis on thrombolytic therapy.
AB  - OBJECTIVE: We studied the influence of the methodologic quality of individual
      trials on the outcome of a landmark meta-analysis on thrombolytic therapy in
      acute myocardial infarction. From each study we extracted the number of patients
      in both groups who died in hospital or during follow-up. Methodologic quality was
      assessed using the Delphi list. We first recalculated pooled odds ratios (ORs)
      and 95% confidence intervals (CIs), on the studies found and compared them with
      the original results of Yusuf et al. Next we incorporated the results of quality
      assessment in five different ways in the calculation of the pooled ORs: a)
      component analysis; b) visual plot; c) quality score as a threshold score; d)
      quality score as a weighting factor; and e) cumulative pooling. RESULTS AND
      CONCLUSION: No correlation between quality scores and ORs was found. Studies with
      a proper description of the different quality components provided an estimate
      close to the true treatment effect. No major differences were found between the
      results of the five different methods of incorporating the quality scores into
      the final conclusion.

PMID- 11987434
TI  - Uncertainty in cost-effectiveness analysis. Probabilistic uncertainty analysis
      and stochastic league tables.
AB  - Interest is growing in the application of standard statistical inferential
      techniques to the calculation of cost-effectiveness ratios (CER), but individual
      level data will not be available in many cases because it is very difficult to
      undertake prospective controlled trials of many public health interventions. We
      propose the application of probabilistic uncertainty analysis using Monte Carlo
      simulations, in combination with nonparametric bootstrapping techniques where
      appropriate. This paper also discusses how decision makers should interpret the
      CER of interventions where uncertainty intervals overlap. We show how the
      incorporation of uncertainty around costs and effects of interventions into a
      stochastic league table provides additional information to decision makers for
      priority setting. Stochastic league tables inform decision makers about the
      probability that a specific intervention would be included in the optimal mix of
      interventions for different resource levels, given the uncertainty surrounding
      the interventions.

PMID- 11987435
TI  - Classic or Bayesian research design and analysis. Does it make a difference?
AB  - OBJECTIVE: The role of classical and Bayesian statistical approaches remains in
      dispute in health services research and policy. The goal of this study was to
      determine if results differ when both analytic techniques are used with the same
      data set. DESIGN: We searched MEDLINE and related databases for English-language
      articles published January 1, 1978 through August 31, 1999. We combined Bayesian
      and classical statistics search terms and their variants with randomized control
      trials (RCTs) and meta-analyses. RESULTS: Searches found 18 studies in 14
      publications that met all review criteria--nine RCTs, eight meta-analyses, and
      one epidemiologic estimate. Statistical analyses using both methods agreed in
      five RCTs, four meta-analyses, and for the epidemiologic estimates. For four RCTs
      where results disagreed, classical analysis found the experimental intervention
      was efficacious compared with the control, and Bayesian reanalysis concluded the
      intervention was not proven efficacious. Classical meta-analyses of the four
      studies where results disagreed concluded the experimental intervention was not
      better than the control; Bayesian reanalysis concluded it was efficacious.
      CONCLUSION: Classical and Bayesian methods in this review exhibited important
      divergence of results. Disagreement on many fundamental beliefs between classical
      and Bayesian statistics means continuing debate. One way to resolve this debate
      is for proponents of each technique to decide together the circumstances for use
      of each method and analytic framework. If the experts do not agree on the
      methodologic requirements, other decision makers likely will force their own
      views.

PMID- 11987436
TI  - Cost-utility analysis of interferon beta-1B in secondary progressive multiple
      sclerosis using natural history disease data.
AB  - OBJECTIVES: Different cost-effectiveness analyses have been presented for
      interferon beta-1b (IFNB) in the treatment of secondary progressive multiple
      sclerosis (SPMS). All studies have used modeling techniques since any effect on
      progression of disability achieved during a clinical trial will last beyond the
      trial. Different approaches to extrapolation have been taken, but generally they
      have been based on disease progression and relapse rates in clinical trials. The
      problem with this approach is that the population in clinical trials is a
      selected group of patients, which has the potential to bias results. A better
      method for extrapolation is to use epidemiologic data. The objective of this
      study is to incorporate natural history data for MS into a previously presented
      cost-utility model and to compare the two methods of extrapolation. METHODS:
      Clinical trial data were used to model disease progression during the first 3
      years in the model. To extrapolate beyond the trial (10 years), data on
      progression of disability were available from a geographically based
      epidemiologic study of the natural history of MS in Canada. There were 568
      patients who had converted to SPMS during the follow-up that were included in the
      data set. Mean costs and utilities for each Markov state were calculated from a
      population-based cross-sectional study in Sweden. RESULTS: The extrapolation
      using clinical trial data appears to have underestimated the progression of
      disability in the long term and thus also the potential benefit of treatment.
      Using the epidemiologic data, the incremental cost per QALY is SEK 257,000 (US
      $25,700; US $1 = SEK 10; November 2000) when all costs (direct, informal care,
      and indirect) are included (discounted 3%). This compares to SEK 342,000 in the
      previous model. The lower cost-effectiveness ratio is mostly due to a larger QALY
      gain with treatment than in the previous model (0.217 compared with 0.162).
      CONCLUSIONS: Cost-effectiveness analysis in SPMS requires that the effect of
      treatment beyond clinical trials be included. The method of extrapolation clearly
      affects the results, and when available, epidemiologic data should be used. Using
      the longitudinal data from Canada, the cost-utility ratios for IFNB-1b in the
      treatment of SPMS appear well within the acceptable range.

PMID- 11987437
TI  - Investigating the structural reliability of a discrete choice experiment within
      health technology assessment.
AB  - This paper investigates the structural reliability of a discrete choice
      experiment within health technology assessment. Two versions of a discrete choice
      experiment, in the form of a self-completion questionnaire, were randomly
      administered to two samples of women who had recently given birth as part of an
      exercise to determine women's preferences for alternative modes of intrapartum
      care. In the first questionnaire, two of the attributes had only their highest
      and lowest levels included, while in the second questionnaire all three levels
      for these two attributes were included. The levels included for all other
      attributes remained the same throughout both questionnaires. The evidence
      relating to the structural reliability of the discrete choice experiment in this
      context was mixed. The results indicated that the relative importance of the two
      attributes in which the levels were varied increased as the number of levels for
      these attributes increased. However, the relative importance of the attributes in
      which the levels were not varied remained relatively stable throughout. The
      results provide evidence in support of a psychological effect whereby respondents
      place more importance upon specific attributes as the number of levels for these
      attributes increases. It is recommended that further research of both a
      qualitative and quantitative nature should be undertaken to assess the potential
      importance (or otherwise) of a psychological effect relating to the number of
      levels chosen for attributes within discrete choice experiments in health
      technology assessment.

PMID- 11987438
TI  - Report from the Swedish Council on Technology Assessment in Health Care (SBU).
      Treatment of alcohol and drug abuse: an evidence-based review.

PMID- 11987439
TI  - How to undertake a clinically relevant systematic review in a rapidly evolving
      field. Magnetic resonance angiography.
AB  - OBJECTIVES: The aim was to determine which generations of the evolving technology
      of magnetic resonance angiography (MRA) are currently of clinical relevance in
      two clinical applications. Our purpose was to plan a systematic review that would
      be valuable both to purchasers driven by cost-effectiveness and to practicing
      clinicians. METHODS: Information was gathered from a search of major
      bibliographic databases, from a short questionnaire sent to 500 U.K. vascular
      radiologists and vascular surgeons, and from local clinical experts. We asked
      which of the MRA techniques were currently used and, assuming availability, what
      would be their technique of choice. RESULTS: There were 206 published articles
      that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight
      (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162
      questionnaires returned (60 radiologists, 102 surgeons). Of the total
      respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis;
      47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced
      techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of
      peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D
      TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use
      MRA, contrast-enhanced techniques were the method of choice. CONCLUSIONS: The TOF
      methods that represent earlier generations of the technology remain clinically
      relevant, and will therefore be included in our systematic review. To ensure
      complete and relevant coverage in reviews of other evolving technologies, it
      would be advisable to obtain data for guidance in a similar way.

PMID- 11987440
TI  - The use of mental health care facilities after stroke. A cost analysis.
AB  - OBJECTIVES: Although psychiatric comorbidity is relevant for a number of
      diseases, it is often ignored in technology assessment. This study examines the
      service use rate in mental healthcare facilities and related costs for stroke
      patients discharged from the University Hospital Maastricht between 1987 and
      1995. METHODS: Through anonymous record linkage, the medical registration of the
      hospital and the registration of the Maastricht Mental Health Care Register were
      linked. RESULTS: Linkage succeeded for 16% of the 2,020 stroke patients,
      indicating that these patients used mental health services during a 10-year
      period around the stroke (+/- 5 years). Of the users' group, 88% had a mental
      healthcare contact following stroke. Regression analysis shows that age, length
      of hospital stay, and mental healthcare contact before stroke are associated with
      mental healthcare use after stroke. It is remarkable in that there is already an
      increase in the consumption of mental health care in the prodromal phase just
      before the stroke occurred. When comparing costs before and after stroke, the
      outpatient costs increased on average by [symbol: see text] 42.64, semi
      institutionalized costs increased on average by [symbol: see text] 208.10, and
      intramural costs by [symbol: see text] 1,189.21. The total increase in costs is
      [symbol: see text] 1,439.95. For all mental healthcare facilities, the increase
      in costs is significant. CONCLUSIONS: No study so far has revealed the total
      costs of mental healthcare facilities following stroke. Extrapolating these costs
      to the Netherlands illustrates that stroke patients have a high psychiatric
      comorbidity, inducing about 1.3% of total mental healthcare costs.

PMID- 11987441
TI  - The economic burden of informal care.
AB  - OBJECTIVES: The great interest focused on home care technologies during the last
      decade resulted from its potential to cut costs. However, the reallocation of
      costs between healthcare providers and social welfare providers, and the indirect
      costs of informal care, are not as frequent topics of discussion. The aim of this
      paper is to discuss different models for estimating the costs of informal care in
      the home care setting in economic appraisals. METHODS: The outcome of using
      different models for estimating indirect costs was illustrated using empirical
      data regarding the time spent by informal caregivers in providing care in a group
      of home care patients (n = 59). The models used comprise different
      interpretations of the traditional human capital approach and the friction cost
      model. RESULTS AND CONCLUSIONS: Informal care is an important component in home
      care. The inclusion of indirect costs of informal care in economic appraisals
      will have implications for the cost-effectiveness of home care, since it will
      raise costs depending on the model used for estimating indirect costs. In this
      study we have shown that indirect costs estimated by the friction cost model only
      amount to 18% to 44% of the cost when the human capital approach is used. The
      results indicate that, regardless of the method used to estimate indirect costs,
      the cost of informal care in evaluations of home care programs is often
      underestimated due to the exclusion of indirect costs.

PMID- 11987442
TI  - Cost and effectiveness of hip protectors among the elderly.
AB  - OBJECTIVE: To characterize the net cost and quality of life effects associated
      with hip protector use among the elderly relative to no intervention. METHODS: We
      developed two deterministic hypothetical cohorts of 500,000 65-year-old women or
      men and followed them over the remainder of their lifetimes. Data inputs were
      collected from secondary sources. Net costs are expressed in 1999 U.S. dollars,
      whereas net effectiveness is expressed in lives saved and in quality-adjusted
      life-years (QALYs) gained. RESULTS: Hip protector use results in net cost savings
      for both elderly women and men. Women over age 65 and men over age 85 also gain
      QALYs through hip protector use. CONCLUSION: Using the estimates available in the
      literature, our analysis indicates that use of hip protectors among women is
      associated with large cost savings and QALY gains even when accounting for the
      inconvenience of using the protectors. Among men, hip protectors are also
      associated with cost savings (although of smaller magnitude), but there are net
      losses of QALYs because of the inconveniences associated with the protectors.

PMID- 11987443
TI  - Cost-minimization analysis of genetic testing versus clinical screening of at
      risk relatives for familial adenomatous polyposis.
AB  - OBJECTIVE: Familial adenomatous polyposis (FAP) is a well-known hereditary
      colorectal cancer-predisposing syndrome. Genetic testing for colorectal cancer
      risk is now part of standard medical practice, but very little is known about the
      economic impact of this technology. The aim of this study was to assess, from a
      healthcare system perspective, the direct costs of two strategies for screening
      at-risk relatives of FAP patients: clinical screening versus genetic testing for
      FAP. METHODS: A systematic review of the literature was carried out. Additional
      information was gathered from experts in research and clinical laboratories and
      in hospital departments. A decision tree was constructed to compare per-person
      and per-family costs of the two strategies for screening at-risk relatives of FAP
      patients. Sensitivity analysis was performed to assess the stability of the model
      across the full range of plausible values for all key parameters. RESULTS:
      According to the decision analysis, with FAP screening starting at puberty, the
      average screening costs are $3,181 and $2,259 (Canadian dollars), respectively,
      for the clinical screening and the genetic testing strategies. Genetic screening
      is cost saving up to a first screening age of 36. Sensitivity analysis shows that
      the results of the baseline analysis hold across a variety of assumptions
      concerning the parameter values. CONCLUSIONS: The genetic testing strategy is
      cost saving relative to the clinical screening alternative. Apart from its lower
      costs, it is associated with many other benefits. Accordingly, under predefined
      conditions, predictive genetic testing seems to be the optimal screening strategy
      for FAP.

PMID- 11987444
TI  - To reuse or not to reuse? An economic evaluation of hemodialyzer reuse versus
      conventional single-use hemodialysis for chronic hemodialysis patients.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of reusing hemodialyzers for
      patients with kidney failure on dialysis employing either a heated citric acid or
      formaldehyde sterilization method, in comparison to the standard practice of
      single-use dialysis. METHODS: A meta-analysis of all relevant studies was
      performed to determine whether hemodialyzer reuse was associated with an
      increased relative risk of mortality or hospitalization. A decision tree was
      constructed to model the effect of three different dialysis strategies (single
      use dialysis, heated citric acid, and formaldehyde dialyzer reuse) on the costs
      and quality-adjusted life expectancy of "typical" hemodialysis patients. The cost
      of heated citric acid reuse was estimated from a center experienced with the
      technique. The cost of end-stage renal disease (ESRD) care, survival data, and
      patient utilities were estimated from published sources. RESULTS: There was
      evidence of a higher relative risk of hospitalization (but not mortality) for
      hemodialyzer reuse compared with single-use dialysis. Depending on the
      assumptions used, the cost savings that could be expected by switching from
      single-use dialysis to heated citric acid reuse were small, ranging from CAN $0
      739 per patient per year. CONCLUSIONS: ESRD programs can incorporate the results
      of this study based on their individual situations to determine whether
      hemodialyzer reuse is appropriate in their setting.

PMID- 11987445
TI  - Health economic evaluations using decision analytic modeling. Principles and
      practices--utilization of a checklist to their development and appraisal.
AB  - OBJECTIVES: Decision analytic modeling allows a rational, feasible, scientific,
      and timely approach to measure the efficiency of new medical technologies in
      health care by using the best available evidence of different sources to produce
      detailed estimates of the clinical and economic consequences of different
      healthcare interventions. The aim of this article has been twofold: first, to
      state the benefit, usefulness, and limitations of decision analytic modeling; and
      second, to propose a list of steps that should be considered when carrying out
      this sort of analysis in order to increase its credibility and validity for
      medical decision making. METHODS: After having read the published literature
      about decision analytic models, a checklist was created, listing the paramount
      items and points that should always be followed when carrying out disease
      modeling. RESULTS: A checklist with 3 items and steps to be taken was drawn up to
      ensure that all important methodologic aspects are considered when performing and
      assessing decision analytic modeling, thereby constituting a standard guide to
      good modeling practices. In addition, a set of limitations inherent to the use of
      decision analytic models is also contemplated, along with a list of
      recommendations increasing their validity and utility. CONCLUSIONS: Health
      economic assessments will continue to be an important tool for the correct
      allocation of resources, and disease analytic modeling will be a potentially
      invaluable tool in assisting decision makers in this task.

PMID- 11987446
TI  - Contact-mediated acceleration of migration of melanoma B16 cells depends on
      extracellular calcium ions.
AB  - The escape of malignant cells from primary tumour and their active migration to
      the surrounding tissues are among the most important steps in the metastatic
      process. During migration, tumour cells interact with neighbouring neoplastic and
      normal cells and such interactions may affect their motile activity. We
      investigated the effect of extracellular calcium ions on migration of mouse
      melanoma B16 cells stimulated by homotypic cell-to-cell contacts. It was found
      that the decreasing of extracellular Ca2+ influx into B16 cells by lowering Ca2+
      concentration in culture medium, or by the application of 0.5 mM La3+ (non
      selective inorganic Ca2+ channels blocker), reduced the contact-mediated
      acceleration of migration of melanoma cells but only slightly affected the basal
      motile activity of non-stimulated single, separated cells moving without contacts
      with neighbouring ones in sparse culture. Since it was suggested that contact
      mediated acceleration of migration of melanoma B16 cells may be controlled by
      mechanosensitive and/or voltage-gated ion channels, the presented data support
      the concept that these channels may affect cell migration by regulation of
      extracellular Ca2+ influx into stimulated cell.

PMID- 11987447
TI  - Effect of wild-type macronucleoplasm transplantation into trichocyst mutant cells
      of Paramecium tetraurelia.
AB  - Approximately 1/2 of the macronucleoplasm of wild-type cells of Paramecium
      tetraurelia was transplanted into d4-84 mutant recipient homozygous for mutations
      nd3a (non-discharging trichocysts) and ts401 (temperature sensitive). After
      injection, 30% of surviving cells shifted from mutant to wild-type phenotype.
      Among the remaining cell lines 29% were unable to eject any trichocysts, and 41%
      discharged less than 10 of them per cell, when tested with picric acid.
      Observations were made through two successive vegetative fissions. These results
      showed that 30% of d4-84 cells contained foreign gene responsible for trichocyst
      discharge and produced cell lines of the wild-type phenotype, in which the
      expression as well as replication of this gene appeared normal.

PMID- 11987448
TI  - A comparative analysis of the rate of meiosis, chiasma frequency and
      terminalization in the Jerboas Allactaga and Jaculus (Rodentia: Dipodidae) in
      Egypt.
AB  - The rate of seven meiotic stages (zygotene-pachytene, diplotene-diakinesis,
      metaphase I, anaphase I, metaphase II, anaphase II, and quartet) was studied in
      the jerboas Jaculus jaculus jaculus, Jaculus orientalis, and Allactaga
      tetradactyla, chiasma frequency and terminalization being examined only in J.
      jaculus and J. orientalis, and compared with the previous data concerning A.
      tetradactyla. Significant differences in the rate of meiosis, frequency of
      bivalent types, and frequency of interstitial and distal or terminal chiasmata
      per genome length were observed between A. tetradactyla and the two congeneric
      species J. jaculus and J. orientalis. Differences of these parameters among
      individuals within each species are also discussed in detail.

PMID- 11987449
TI  - Chromosome polymorphism and C-banding variation of the brachypterous grasshopper
      Podisma sapporensis Shir. (Orthoptera, Acrididae) in Hokkaido, northern Japan.
AB  - The grasshopper Podisma sapporensis consists of two main chromosome races in
      Hokkaido. The western group of populations of P. sapporensis, belonging to the XO
      race, has a diploid number of chromosomes 2n = 23 in the male and 2n = 24 in the
      female (sex determination XO male/XX female). The eastern group of populations of
      this species, belonging to the XY race, differs from the western one as a result
      of Robertsonian translocation between the originally acrocentric X chromosome and
      M5 autosome in homozygous state, having resulted in the forming of chromosome sex
      determination neo-XY male/neo-XX female (2n = 22). These races are geographically
      isolated by the mountainous system consisting of the Mts Daisetsu and Hidaka
      range, occupying the central part of the island. The hybrid zones between the
      races have not so far been discovered. Various levels of polymorphism for the
      pericentric inversions and C-banding variation exist in different chromosomes
      throughout populations in both chromosome races. In some solitary populations
      (the population at the summit of Mt Yotei, populations in the vicinity of
      Naganuma, Oketo, and Tanno) pericentric inversions are fixed in some pairs of
      chromosomes, which enables marking of the discrete karyomorphes. In the Mt
      Daisengen population all chromosomes are two-armed as a result of fixing the
      pericentric inversions. These facts contradict karyotypical conservatism of the
      tribe Podismini. The level of diversity of P. sapporensis karyotypes could
      provide a new perspective on the evolutionary process of different karyotype in
      Orthoptera. The considerable occurrence of polymorphism in chromosomes suggests
      that karyotypic diversification is undergoing in P. sapporensis. The authors also
      proposed that P. sapporensis would be divided into four chromosome subraces in
      the XO chromosome race and two chromosome subraces in the XY race, on the basis
      of karyotypic features. These races may have been established by fundamental
      climatic changes during the glacial epoch.

PMID- 11987450
TI  - The karyotypes of two bark-lice species (Psocoptera, Psocomorpha, Amphipsocidae):
      the first description of the neo-XY sex chromosome system in Psocoptera.
AB  - Karyotypes of two bark-lice species Amphipsocus japonicus End. and Dasypsocus
      japonicus End. (Amphipsocidae, Psocomorpha, Psocoptera) were studied for the
      first time. D. japonicus displayed 2n = 16 (14 + XX/X0). The XX/X0 sex chromosome
      system observed in this species is characteristic of the order Psocoptera. A.
      japonicus showed 2n = 16 (14 + neo-XY). This is the first observation of the neo
      XY sex determination system in Psocoptera. In this species a large amount of
      constitutive heterochromatin was found in the original X-part of the neo-X
      chromosome.

PMID- 11987451
TI  - Chromosome banding in Cacopsylla mali (Schmidberger) and Cacopsylla sorbi
      (Linnaeus) (Homoptera, Psyllidae) with polymorphic sex chromosomes.
AB  - C-banding and Ag staining were applied to Cacopsylla sorbi and C. mali. The aim
      was to discover some additional cytological markers to follow the pathways of the
      sex determination system transformation in the evolution of the species. Of three
      karyotype patterns so far described in the literature for these species--a type A
      (XO), B (neoXY) and C (neoX1X2Y), only the last two types (B and C) were found.
      All 6 studied Cacopsylla sorbi from Finland had a karyotype of type B (2n = 20 +
      XY), while C. mali had both types. Type B (2n = 22 + XY) was observed in 31
      males, whereas type C (2n = 20 + neoX1X2Y) in the remaining four. The karyotype
      of C. sorbi was found to be characterized by a very small amount of C-positive
      material, localized in a telomere of the Y chromosome. The karyotype of C. mali
      was also characterized by a very small amount of C-banded material. Both the sex
      chromosomes and the autosomes displayed a marked polymorphism of C-positive bands
      within different individuals and even the same individual. In both species the
      nucleolus was located in the telomere of a middle sized autosomal till diplotene
      inclusive. The C-banding and Ag staining in the studied Cacopsylla species did
      not provide any additional cytological markers for an understanding of the
      pathways of sex determination system transformation in the evolution of the
      species.

PMID- 11987452
TI  - Cytotaxonomic characteristics of the genus Glyptotendipes Kieffer (Chironomidae,
      Diptera) from fish and retention ponds (Silesia, southern Poland).
AB  - The cytotaxonomic characteristics of species of the genus Glyptotendipes
      (Chironomidae): G. glaucus Meigen, G. paripes Edwards, and G. barbipes (Staeger)
      are described. The studied material was collected from a fish pond at Golysz and
      a sewage retention pond at Chybie in Silesia. All the studied species have the
      chromosome set 2n = 8, but with many specific structural and functional changes.
      The cytogenetic data of G. glaucus showed that the studied specimens of this
      species have been produced by the introgressive hybridization of two sibling
      species: G. glaucus x G. pallens, and subsequent crossing-over in the hybrid
      chromosome CD. Owing to this process, the band pattern of chromosome arm D
      coincided with those of G. pallens. New aberrations (homo- and heterozygous
      deletions in arm G as well as heterozygous inversions in chromosome arm B) were
      detected in G. glaucus. Specific band sequences were discovered in chromosomes of
      G. paripes. The band patterns established in chromosomes AB and G of this species
      were identical with those of Siberian populations. The banding patterns of the
      polytene chromosomes of G. barbipes do not differ from the standard. However,
      high frequency of pericentric inversion of chromosome AB was established. Many
      new puffs were found in the polytene chromosomes of all the studied species.
      Their nucleolar organizer was very sensitive to environmental changes. In G.
      glaucus it appeared in three different states: very active, slightly active, and
      heterozygous state. The organic pollution existing in the sewage retention pond
      may contribute to possible mutations and chromosomal damage in Glypotendipes
      species. Structural and functional rearrangements of the polytene chromosomes of
      these species mobilized their genomes and provide for survival under polluted
      conditions.

PMID- 11987453
TI  - C-banded karyotypes of some dragonfly species from Russia. II. The families
      Cordulegasteridae, Corduliidae and Gomphidae.
AB  - The C-stained karyotypes of five species of three dragonfly families from Western
      Siberia and Kunashir Island have been analysed. Gomphus epophtalmus Sel., G.
      vulgatissimus (L.), Nihonogomphus ruptus (Sel. et Hag.) (Gomphidae), and
      Anotogaster sieboldii (Sel.) (Cordulegasteridae) showed usual character of C
      heterochromatin distribution, all chromosomes have terminal C-bands. Somatochlora
      graeseri Sel. (Corduliidae) has unique for dragonflies type of terminal C-blocks
      on autosomes. Three pairs of autosomes have the very large heterochromatic
      blocks, other chromosomes, including the X, have no C-band.

PMID- 11987454
TI  - C-bands on chromosomes of four beetle species (Coleoptera: Carabidae, Silphidae,
      Elateridae, Scarabaeidae).
AB  - The C-banding pattern of Bembidion geniculatum, Silpha atrata, Prosternon
      tesselatum, and Epicometis hirta are presented. All analysed species have
      pracentromeric C-bands on autosomes and chromosome X but the widest ones are
      visible in the karyotype of B. geniculatum. In S. atrata, P. tesselatum, and E.
      hirta sex chromosome y is heterochromatic, only B. geniculatum having the Y
      chromosome wholly euchromatin. The results indicate that on the chromosomes of
      the investigated species do not have a terminal and an intercalar segments of
      heterochromatin.

PMID- 11987455
TI  - Embryonic fissure and photoreceptor differentiation in the eye of adult Garra
      rufa Heckel 1843 (Cyprinidae, Teleostei).
AB  - The retina of the adult teleost Garra rufa retains a curved, open embryonic
      fissure indicating an asymmetrical postembryonic retinal growth.
      Undifferentiated, oval photoreceptors are observed on both sides of the middle of
      the fissure with their larger diameter running parallel to the fissure to which
      they may attach by desmosomes. They detach from the fissure, rotate to become
      perpendicular to it and begin an active process of differentiation as they slide
      along the temporal side of the outer half of the fissure. This process is divided
      into stages for simplicity. The photoreceptors develop stumpy inner segments
      extending into a ventricular space that appears between the retinal pigment
      epithelium and the photoreceptors. Calycal processes arise from the inner
      segments and the distal centriole of each photoreceptor forms a connecting
      cilium. The proximal centriole is retained for some time after the outer segment
      develops. The formation of rod spherules and cone pedicles takes place almost
      concomitantly with the outer segments. Double cones appear first as single cones
      before pairing. One or more of the principal cone mitochondria accumulate
      electron-dense material and merge to form the ellipsosome. The retinal pigment
      epithelium undergoes a parallel differentiation. The developmental events
      described in the present work conform those recorded in embryonic teleostean
      retinas.

PMID- 11987456
TI  - Structure of ovarioles in adult queens and workers of the common wasp, Vespula
      germanica (Hymenoptera: Vespidae).
AB  - The ovaries of the common wasp, Vespula germanica are polytrophic-meroistic and
      consist of 2-3 (workers) or 7 (queens) ovarioles. The ovarioles are
      differentiated into three regions: a terminal filament, a germarium, and a
      vitellarium. The germaria of both castes consist of two zones: an anterior zone
      of germ-cell cluster formation and a posterior one of germ-cell cluster
      differentiation. The vitellaria comprise 4-6 (workers) or 7-10 (queens) ovarian
      follicles (egg chambers). Each chamber consists of an oocyte and about 60
      isodiametric nurse cells (trophocytes). The egg chambers have been arbitrarily
      classified into four developmental categories: early and late previtellogenic,
      vitellogenic, and choriogenic. The process of oogenesis in workers proceeds only
      up to the onset of the late previtellogenesis. Neither vitellogenic nor
      choriogenic egg chambers were observed in this caste. During early and late
      previtellogenesis the envelope of the oocyte nucleus proliferates and becomes
      highly folded. This process leads to the formation of characteristic organelles,
      termed accessory nuclei (AN). Although AN arise in the oocytes of both queens and
      workers, their number in the latter caste is always considerably lower. At the
      onset of the late previtellogenesis AN start to migrate towards the periphery of
      the oocyte where they reside till the end of oogenesis. The physiological state
      of the worker ovaries is discussed in the light of the presented results.

PMID- 11987457
TI  - Development of terminal filaments and ovariole envelopes in Thermobia domestica
      (Insecta, Zygentoma) larvae.
AB  - The 3rd instar female larvae of Thermobia domestica have five pairs of gonad
      primordia, each enclosed within a basal lamina (tunica propria). At the end of
      the 3rd instar some somatic cells scattered on the outer surface of the lamina
      are seen. During the 4th larval instar the gonad primordia start to form the
      ovarioles. Each ovariole is elongated and polarized, having anterior and
      posterior ends. The anterior group of outer somatic cells proliferate to form the
      terminal filament. At the 6th larval stage the ovarioles are already formed. The
      terminal filament is separated from the germarium by a thick basal lamina
      (transverse septum). There are three types of cell building the terminal
      filament. 1/Basal cells with numerous fingerlike projections; 2/Cells with
      electron lucent cytoplasm and large nuclei, and 3/Cells with darker cytoplasm
      containing bundles of fibers and more compact nuclei. The outer surface of the
      filament is covered by a thick, fibrous basal lamina. The somatic cells that in
      the previous stages were scattered on the tunica propria as distinct cells, in
      the 6th larval stage form a cellular envelope (tunica externa). This envelope is
      formed by a layer of flat cells, and contains numerous tracheae.

PMID- 11987458
TI  - Intercellular cytoplasm transport during oogenesis of the moth midge, Tinearia
      alternata Say (Diptera: Psychodidae).
AB  - Polytrophic ovaries of the nematocerous dipteran, Tinearia alternata Say consists
      of several developmentally synchronized ovarioles each housing only one
      functional egg chamber with 15 nurse cells and an oocyte. At the early stages of
      previtellogenesis the nurse cells become polyploid and synthetically active.
      Their nuclei contain polytene chromosomes and prominent nucleoli. With the
      advance of previtellogenic growth the nurse cell cytoplasm is loaded with the
      growing number of ribosomes and contain perinuclear nuage material, mitochondria,
      electron dense bodies and aggregations of endoplasmic reticulum. All these
      organelles are transported into the oocyte thanks to the massive and rapid flow
      of the nurse cell cytoplasmic contents. Nurse cell-oocyte transport is mediated
      by actin cytoskeleton. Prior to the rapid cytoplasm transfer, F-actin network is
      associated with the nurse cell membranes while tiny bundles of microfilaments
      form actin baskets connected with ring canals. Nurse cells in Tinearia lack an
      extensive scaffold of radially oriented, F-actin bundles (cables) that would
      tether their nuclei in place, thus preventing ring canals from plugging. The way
      the nuclei are anchored to their central positions within the cells remains
      unclear. Towards the final stages of oogenesis nurse cells are almost devoid of
      cytoplasm and degenerate. Although their nuclei undergo dramatic morphological
      transformations, typical hallmarks of apoptotic pathway could not be clearly
      observed. Rapid ooplasmic streaming does not occur.

PMID- 11987459
TI  - Structure and development of ovaries in the weevil, Anthonomus pomorum
      (Coleoptera, Polyphaga). I. Somatic tissues of the trophic chamber.
AB  - In developing ovarioles of Anthonomus pomorum (Coleoptera, Polyphaga,
      Curculionidae) the trophic chambers (tropharia) are relatively large and consist
      of clusters (clones) of germ cells and various somatic tissues. Each ovariole is
      enclosed within an outer epithelial sheath (tunica externa). Throughout the pupal
      phase, the growth of this sheath is accelerated and precedes the development of
      the rest of the ovariole. As a result, the epithelial sheath proliferates
      anteriorly and forms an elongated "sleeve" that during the later stages of
      development becomes gradually filled by the growing tropharium. In the early
      pupal stage, a few terminal filament cells are observed in contact with the
      anterior end of the tropharium. These cells are separated from the rest of the
      trophic chamber by a transverse septum, which maintains continuity with the basal
      lamina. Beneath the basal lamina there is a layer of inner sheath cells, whereas
      inside the tropharium there are interstitial cells. These two types of cell
      differ morphologically in a mature ovary but they retain, until the end of the
      imago-B stage, a similar ultrastructure testifying to their common origin. At the
      posterior end of the tropharium, from the imago-B stage on, many young oocytes,
      surrounded by prefollicular cells, are observed. This is the so-called neck
      region of the tropharium. Extraction with Triton X-100 detergent showed that in a
      mature trophic chamber there are only individual microtubules arranged along the
      projections of interstitial cells. This indicates that the cytoskeleton elements
      (microfilaments and microtubules) participate only to a very limited extent in
      the spatial organisation of the tropharium in A. pomorum.

PMID- 11987460
TI  - Zooplankton in the ponds with tropical plants in the greenhouses of the Botanical
      Garden of the Jagiellonian University in Krakow.
AB  - The presence of P. tetraurelia was found in the pond in "The Palm-House"
      greenhouse.

PMID- 11987461
TI  - The Paramecium aurelia species complex in Ukraine.
AB  - New habitats of Paramecium biaurelia were found in the Gorgany Mts, Eastern
      Carpathians.

PMID- 11987462
TI  - Paramecium aurelia species complex in the catchment area of the River Raba
      mountain course (the Carpathians).
AB  - In the water bodies of the Beskid Wyspowy Mts three species of the Paramecium
      aurelia complex have been found, i.e. P. biaurelia, P. tetraurelia and P.
      novaurelia. P. tetraurelia, which in Europe is a very rare species, was for the
      first time recorded in this region of the Carpathians.

PMID- 11987463
TI  - Genetic differentiation of the two subspecies of the smooth newt inhabiting
      Romania, Triturus vulgaris vulgaris and T.v. ampelensis (Urodela, Salamandridae)
      as revealed by enzyme electrophoresis.
AB  - Starch gel electrophoresis was applied to quantify genetic variation and
      divergence in samples from Romanian populations of the nominal form of the smooth
      newt Triturus vulgaris and those of the endemic Romanian subspecies T.v.
      ampelensis, a population from a parapatric area was additionally included. All
      the samples had similar levels of genetic variation measured by the mean
      heterozygosity, proportion of polymorphic loci, and mean number of alleles per
      locus. T.v. ampelensis samples were genetically clearly different from the
      nominal form samples, the mean genetic distance between the two subspecies was
      being estimated as DN = 0.114. No fixed differences in allele composition between
      the two subspecies were found, although some of the alleles were found either
      exclusively in the nominal form (Aat-1) or in T.v. ampelensis (Mpi a). Other
      alleles at these loci together with Mdh-1 differed markedly in frequency. The
      population from the parapatric area was intermediate in allelic composition, but
      grouped together with the T.v. ampelensis samples in a maximum likelihood tree
      (99.7% bootstrap support for this grouping). The data indicate that the two
      subspecies interbreed in a parapatric zone. The molecular clock applied to
      electrophoretic data indicates that these two forms split during the Pleistocene.

PMID- 11987464
TI  - The occurrence DNA of Babesia microti in ticks Ixodes ricinus in the forest areas
      of Szczecin.
AB  - Babesia microti, an intraerythrocytic protozoan and the etiological agent of
      human babesiosis, is transmitted by the bite of the tick, Ixodes ricinus. The aim
      of the present study was to confirm the presence of B. microti by detection of
      the DNA of these protozoans. The prevalence of B. microti was studied using the
      PCR method with primers complementary to the gene fragment encoding nuclear small
      subunit ribosomal RNA (ss-rDNA). In the course of this study a total of 2095
      ticks, Ixodes ricinus, were examined. The mean infection rate was 6.2%. Variable
      prevalance values were also obtained from six different locations and they were
      further modified by the seasons of the year. The results confirmed the competence
      of I. ricinus as a vector of B. microti and that a B. microti-specific PCR can
      provide a sensitive test for laboratory detection of babesiosis.

PMID- 11987465
TI  - Expression of human blood group antigens A and B in kidney and lung of some
      vertebrates.
AB  - Human blood group antigens (BGA) are genetically determined glycoproteins found
      in many cells and tissues of different mammals. Their major biological functions
      are still undefined. There are few investigations analysing the evolutionary
      aspect of BGA tissue distribution. The present study is aimed at examining the
      expression of human A and B antigens in the kidney and lung of some free-living
      vertebrates. The biotin-streptavidin-peroxidase immunostaining system was applied
      on kidney and lung paraffin sections derived from free-living representatives of
      five different vertebrate classes. Excluding the possibility of any non-specific
      staining by the application of inhibition tests, A and B antigens were
      demonstrated most constantly in epithelial cells of renal and respiratory
      tubules. They were also detected in chondrocytes of fish gills, in some muscular
      and endothelial cells. Single erythrocytes showed a positive cytoplasmic staining
      only in some higher vertebrates. Human BGA seem to be conserved carbohydrate
      structures with biological functions probably related to cell integrity and
      differentiation.

PMID- 11987466
TI  - Adrenal steroids act as inhibitory modulators of thyrofollicular cell morphology
      and proliferation in neonatal chicks (Gallus domesticus).
AB  - In the present study the effects of adrenal corticoids, both natural and
      synthetic, namely cortisol and dexamethasone respectively, was observed on the
      thyroid gland cell morphology and proliferation in neonatal male chicks (Gallus
      domesticus). Cortisol was injected at a dose of 4 mg/100 g body weight and
      dexamethasone at a dose of 1 mg/100 g b.w. subcutaneously daily for fifteen
      consecutive days. The control birds were similarly injected with normal saline at
      a daily dose of 0.2 ml per bird for the same time period. The results indicated
      that both cortisol and dexamethasone caused a significant decrease in
      thyrofollicular cell height. On the contrary, a significant increase in the ratio
      of the follicular diameter to the number of nuclei per follicle i.e. D/N value
      was observed in both cortisol and dexamethasone treated chicks. It was also
      observed that both cortisol and dexamethasone induced suppression of mitotic
      activity, as evidenced from a significant decrease in mitotic percentage compared
      with the control chicks. The present authors' studies thus indicate that adrenal
      corticoids act as inhibitory modulators of thyroid follicular activity as regards
      karyomorphology and cell proliferation.

PMID- 11987467
TI  - Presence of histamine and mast cells in chicken oviduct.
AB  - The purpose of the present study was: (1) to demonstrate immunocytochemically the
      localization of histamine in the wall of four chicken oviductal parts, i.e.
      infundibulum, magnum, isthmus, and shell gland, (2) to identify the presence of
      mast cells in chicken oviduct, and (3) to determine histamine concentration in
      oviductal tissue by the spectrofluorometric method. Experiments were carried out
      on Isa Brown laying hens decapitated just after oviposition. The specific immuno
      reactivity for histamine and the presence of mast cells were found in the wall of
      all the examined oviductal parts. The immuno-reactive histamine was localized in
      epithelium, tubular glands, connective tissue layer, circular and longitudinal
      muscles, and endothelium and muscles of blood vessels. The intensity of immuno
      positive reaction was as follows: infundibulum > shell gland > magnum = isthmus
      and correlated with quantitatively determined histamine level and tissue density
      of mast cells. It is suggested that mast cells are the main source of histamine
      in the chicken oviduct.

PMID- 11987468
TI  - Electrophysiological effect of ruthenium red and pH on the skin of the edible
      frog, Rana esculenta L.
AB  - Amphibian skin is a sensitive interface between the organism and the environment.
      Metal ions from the external environment, some of them being trace elements, act
      on the amphibian skin. It had been shown that stimulation of tactile receptors
      affected Na+ transport in the frog skin and changed the potential difference,
      therefore the aim of this project was to study the effect of ruthenium complex,
      known as ruthenium red (RR), on the ion transport in this organ in vitro under
      control conditions, after mechanical stimulation and also in the presence of the
      Na+ transport inhibitor-amiloride. Three different concentrations of RR (0.12,
      1.2, and 12.0 mM) in two different pH values (6.4 and 7.4) were studied in vitro
      in the Ussing apparatus. The measured electrophysiological parameters were the
      transepithelial electrical potential difference (PD) and the changes in PD after
      mechanical stimulation (dPD). The gentle mechanical stimulus was a jet of bath
      fluid from a peristaltic pump directed on the mucosal surface of isolated frog
      skin. After mechanical stimulation, transient hyperpolarization invariably
      occurred (dPD = 1.5 +/- 0.2 mV). In the presence of RR the hyperpolarization was
      smaller and this diminution was concentration dependent: 0.5 +/- 0.1 mV for 1.2
      mM of RR and 0.1 +/- 0.1 mV for 1.2 mM of RR. At pH 6.4 the reactions of the
      skins on the mechanical and chemical stimuli were smaller, in the presence of
      amiloride disappearing completely, but after the washing away of amiloride from
      the experimental organ in pH 6.4 the action of RR was stimulatory. The natural
      defensive reactions of frog skin related to the ion transport and electrical
      potential difference are affected or disappear in the presence of ruthenium
      complex.

PMID- 11987469
TI  - The site of aromatization in the mouse cryptorchid testis.
AB  - Using the mouse cryptorchid model, degenerations of germ cells were observed as
      well as a reduced size of seminiferous tubules, while the area of the
      interstitial tissue increased. Aromatase, the enzyme responsible for the
      conversion of androgens into oestrogens, was immunolocalized in Leydig cells and
      in germ cells from both scrotal and abdominal testes, and in Sertoli cells only
      in a control testis. In the cryptorchid testis, aromatase was strongly expressed
      in a few tubules, including those spermatids that were still present. Other cells
      inside the tubules were negative for aromatase. In both testes, oestrogen
      receptors alpha were expressed only in Leydig cells. Strong aromatase expression
      in germ cells indicates an additional source of oestrogens in the testis besides
      the interstitial tissue.

PMID- 11987470
TI  - Variation in the ovarian and plasma progesterone and estradiol levels of the
      domestic hen during a pause in laying.
AB  - Little is known about the physiological events occurring in the chicken ovary
      during a pause in laying, therefore the aim of the present study was to examine
      changes in sex steroid concentration in the follicle wall and blood plasma during
      cessation of egg laying. The experiment was performed on laying Isa Brown hens.
      Control hens were fed ad libitum whereas the experimental ones were subjected to
      a pause in laying by complete food deprivation for 5 days and water deprivation
      on 3 day followed by feeding every second day up to 9 day and then ad libitum.
      Blood samples were taken from the wing vein each day. The hens were decapitated
      on day 3, 6, 9, and 16. The ovary was isolated and the following follicles were
      dissected: white (1-2; 2-4; 4-6; 6-8 mm) and yellow preovulatory ones (F1-F3).
      Progesterone and estradiol were measured in the follicle wall and blood plasma by
      RIA methods. The hens stopped egg laying on day 4 and began egg restoration on
      day 14 of the experiment. Cessation of egg laying was preceded by a decrease in
      estradiol and progesterone levels in the ovary as well as in the blood plasma.
      The plasma level of these steroids began to increase 7 days before the start of
      egg restoration. Autopsy of the ovary showed that the atrophy of the chicken
      yellow preovulatory follicles during the pause in laying was accompanied by a
      significant increase in the total number of white follicles.

PMID- 11987471
TI  - An interesting case of gynandromorphism in Andrena helvola (Linnaeus, 1758)
      (Hymenoptera: Apoidea: Andrenidae).
AB  - A gynandromorphic specimen of Andrena helvola (Linnaeus, 1758) having secondary
      sexual characters on the head is described.

PMID- 11987472
TI  - Eating disorders.

PMID- 11987473
TI  - Pharmacologic treatment of eating disorders.
AB  - OBJECTIVE: Eating disorders are a serious group of conditions that affect 3% of
      women in industrialized nations over their lifetimes. Recent years have seen
      considerable progress in the treatment of these disorders. This article reviews
      the current body of evidence for the pharmacologic treatment of eating disorders.
      METHODS: We undertook a literature review. RESULTS: For patients with anorexia
      nervosa (AN), drug trials have been disappointing. In contrast, numerous studies
      have demonstrated a clear role for antidepressants in the treatment of bulimia
      nervosa (BN). Pharmacologic investigations of binge eating disorder (BED), a more
      recently defined entity, have identified several promising drugs. There is also
      support for the utility of combined medication and psychotherapy. CONCLUSION:
      Continued research efforts are necessary, particularly regarding the long-term
      effects of therapy and the development of new pharmacologic strategies.

PMID- 11987474
TI  - Psychological treatments for anorexia nervosa: a review of published studies and
      promising new directions.
AB  - OBJECTIVE: To review the existing literature on the psychological treatments for
      anorexia nervosa (AN), especially randomized clinical trials that have been
      published. In addition, new psychological approaches will be described. METHODS:
      An extensive literature review was conducted to identify the psychological
      treatment trials on AN that have been published over the past 3 decades. RESULTS:
      Fewer than 20 controlled clinical trials were identified, evaluating the
      effectiveness of various types of psychotherapy in AN treatment. Evidence for the
      effectiveness of these interventions, with the exception of family therapy for
      younger patients with shorter duration of illness, remains questionable.
      Promising new approaches include motivational enhancement therapy and
      psychotherapies aimed at relapse prevention. CONCLUSION: Currently, there is
      little empirical evidence on which to base treatment decisions regarding the
      psychological treatments for AN. There is a desperate need for further research
      in this area, especially examining relapse prevention and motivational
      enhancement strategies for AN.

PMID- 11987475
TI  - Acute psychiatric inpatient care for people with a dual diagnosis: patient
      profiles and lengths of stay.
AB  - OBJECTIVE: This study describes characteristics of psychiatry inpatients with
      developmental disabilities (DD) and their admissions to psychiatry wards in 2
      acute care hospitals. It also compares differences in lengths of stay between
      admissions of this group with a comparison sample of inpatient admissions without
      DD. METHOD: A retrospective chart review was conducted on all individuals with DD
      who were psychiatric inpatients at 2 Kingston, Ontario, general hospitals, within
      a 4-year period (1994 to 1998). A comparison sample of admissions of patients
      without DD was chosen. Frequency tables were used to describe the inpatients with
      DD and to describe the 2 samples of admissions. Nonparametric statistics were
      used to compare the median length of stay between the 2 samples. Associations
      between length of stay and other covariates were explored within the sample of
      patient admissions with DD. RESULTS: The 62 individuals with DD had 101
      admissions over the study period. Suicidal ideation was the most common admission
      reason (46%), and mood disorder was the most common discharge diagnosis (29%).
      The median length of stay for patients with DD was 8 days, which did not differ
      meaningfully from the comparison sample. Variables that were significantly
      associated with length of stay among individuals with DD included sex, referral
      source, and diagnosis. CONCLUSION: When individuals with DD are psychiatric
      inpatients, their length of stay is affected by some factors that have been
      identified in previous studies not specific to DD (for example, referral source
      and diagnosis). Our finding that male patients with DD have longer lengths of
      stay than do female patients in the same sample has not been reported in previous
      research.

PMID- 11987476
TI  - Canadian geriatric psychiatrists: why do they do it? A Delphi study.
AB  - OBJECTIVE: To generate hypotheses regarding influential factors that have
      contributed to the practice of geriatric psychiatry by geriatric psychiatrists.
      METHOD: Using the Delphi technique, designed to generate ideas and consensus, a
      sample of members of the Canadian Academy of Geriatric Psychiatry (CAGP) was
      asked to provide ideas on what factors were influential in their decision to
      devote a significant part of their practice to geriatric patients. These items
      were then synthesized into a questionnaire and rated for their degree of
      influence by the same group of psychiatrists. RESULTS: A total of 41 items were
      rated according to their degree of influence. The most influential items were
      related to geriatric psychiatry residency training experiences that were
      perceived to be positive or adequate. Supervision characteristics and interest in
      the medical psychiatric nature of the field were also deemed influential.
      CONCLUSIONS: This study generates the hypothesis that the nature of the
      educational experience during psychiatry residency has a significant influence on
      the practice of geriatric psychiatry.

PMID- 11987477
TI  - Relation of blood counts during clozapine treatment to serum concentrations of
      clozapine and nor-clozapine.
AB  - OBJECTIVE: To determine the relation between serum clozapine and nor-clozapine
      levels and blood cell counts during clozapine treatment. METHOD: We undertook a
      prospective longitudinal study of 37 consecutive patients with a diagnosis of
      schizophrenia treated with clozapine. We obtained informed consent and then
      determined serum concentrations of clozapine and nor-clozapine weekly. Clozapine
      was administered daily in divided doses given every 12 hours and adjusted
      according to clinical guidelines for its use. Samples for serum concentrations
      were taken at steady state, immediately before the next morning's dose, for 4 to
      8 weeks. Complete blood counts (CBC), weight, and vital signs (that is, blood
      pressure, pulse, and temperature) were also monitored weekly before the morning's
      dose of clozapine was administered. RESULTS: Analyses of variance showed no
      significant changes over the 8-week treatment course in the observed mean white
      blood count (WBC), red blood count (RBC), neutrophils, and lymphocytes counts, or
      in the hemoglobin and hematocrit. Only a few weak correlations (r < 0.21) were
      found between these hematological parameters and the measures of serum clozapine
      and nor-clozapine. CONCLUSIONS: The mechanism of clozapine-induced hematotoxicity
      at the therapeutic dosage range is probably not by direct toxicity of clozapine
      or nor-clozapine to the blood cells or their precursors. The formation of the
      cytotoxic nitrenium compound from clozapine by neutrophils may be necessary.

PMID- 11987478
TI  - Breaking up is hard to do: the heartbreak of dichotomizing continuous data.
AB  - Researchers often take variables that are measured on a continuum and then break
      them into categories (for example, above or below some cut-point), either to
      place subjects into groups or as an outcome measure. In this article, we show
      that the rationales given for this practice are weak and that categorization
      results in lost information, reduced power of statistical tests, and increased
      probability of a Type II error. Dichotomizing a continuous variable is justified
      only when the distribution of that variable is highly skewed or its relation with
      another variable is nonlinear.

PMID- 11987479
TI  - Treatment resistance in anorexia nervosa and the pervasiveness of ethics in
      clinical decision making.
AB  - Clinical efforts to treat anorexia nervosa (AN) are constantly resisted by
      patients. Although the primacy of patient autonomy is a cornerstone of modern
      medical ethics, clinicians will nonetheless often be justified in pursuing
      particular interventions despite such resistance, give the reduced competency of
      patients suffering from this multifactorial psychiatric illness. While a
      literature exists on the ethical justification for imposing treatment, that
      literature has focused exclusively on situations in which patients refuse
      treatment outright. When patients resist rather than refuse treatment, clinicians
      are faced with the ethical challenge of deciding whether particular interventions
      constitute justified infringements upon patient autonomy. Given the fact that
      treatment resistance is endemic to AN, we see that ethical decision making must
      also be a continual part of the disorder's treatment. This paper argues that the
      treatment of AN merely constitutes a particularly clear example of what is in
      fact a general phenomenon: ethical decision making pervades all clinical
      practice.

PMID- 11987480
TI  - Topiramate use in obese patients with binge eating disorder: an open study.
AB  - OBJECTIVE: To assess topiramate's efficacy and tolerability in a group of obese
      binge eaters with no neuropsychiatric comorbidity. METHOD: We consecutively
      selected 8 obese patients with binge eating disorder (BED) and no medical or
      psychiatric comorbidity from individuals seeking treatment for obesity. Treatment
      with topiramate at 150 mg daily was administered over a 16-week period. To assess
      outcome, we employed the days with binge episodes per week (DBE), the Binge
      Eating Scale (BES), the Beck Depression Inventory (BDI), and body weight
      evaluation. RESULTS: Of the 6 patients who completed the trial, all showed
      reduced binge eating. Four patients presented a total remission, and 2 had a
      marked reduction in binge eating frequency. The mean DBE decreased significantly
      from 4.3 to 1.1 (P = 0.03), as did the BES scores, which fell from 31.8 to 15.3
      (P = 0.04). Moreover, there was a statistically significant weight loss (mean 4.1
      kg, P = 0.04). The most frequent side effects were paresthesias, fatigue, and
      somnolence. CONCLUSION: Topiramate may be an effective and well-tolerated agent
      in the treatment of BED in obese patients.

PMID- 11987481
TI  - Re: Who develops severe or fatal adverse drug reactions to selective serotonin
      reuptake inhibitors?

PMID- 11987482
TI  - Re: Canadian and American psychiatrists' attitudes toward dissociative disorder
      diagnoses.

PMID- 11987483
TI  - Acute onset of schizophrenia following autocastration.

PMID- 11987484
TI  - The World Trade Center disaster.

PMID- 11987485
TI  - Selenium, thyroid hormones, mood, and behaviour.

PMID- 11987486
TI  - [Systemic viral infections: conditions, etiology, diagnosis].
AB  - Etiological, epidemiological and immunological conditions of human virus
      infections have been summarized. The main etiopathological aspects and basic
      etiological diagnostics of systemic infections were discussed with special
      reference to neurological, enteric, cardiac, pulmonary, ocular and sexually
      transmitted infections. The importance of safety laboratory conditions was
      underlined.

PMID- 11987487
TI  - [CA-125 antigen].
AB  - This review describes the physicochemical and biological properties of antigen
      CA125 and clinical utility of antigen in oncologic diagnostic. CA125 is the most
      reliable marker for ovarian cancer in clinical practice. Analysis of CA125 values
      performed by many authors revealed its highest concentrations in serous and
      endrometrioid histological type. Serial measurements of CA125 are useful in
      monitoring the response to chemotherapy and follow-up the early detection of
      recurrent disease of patients with ovarian cancer.

PMID- 11987488
TI  - [Interaction of T lymphocytes with elastin and their significance in
      immunopathology].
AB  - Recent data indicate that human T lymphocytes can adhere to elastin and respond
      to co-stimulatory signals of that protein. This reactivity is mediated by non
      integrin receptor, elastin binding protein. In addition, another receptor
      belonging to integrin family may be also involved. T cell interactions with
      elastin (but not other extracellular matrix proteins) appear to be upregulated in
      healthy males and at least some patients with vasculitis. Interestingly, statins
      in pharmacological concentrations strongly and selectively block those
      interactions. Our data point to the potential role of T cell interactions with
      elastin in immunopathology of vasculitis and atherosclerosis.

PMID- 11987489
TI  - [The role of nitric oxide in pathogenesis of essential hypertension].
AB  - It is known that NO is involved in a variety of physiological functions including
      the regulation of blood pressure. Dysregulation of L-arginine/NOS/NO biological
      activity occurs in blood hypertension. The present review will focus on a
      significance of NO in pathogenesis of essential hypertension.

PMID- 11987490
TI  - [Liver regeneration after partial hepatectomy. Role of lipid mediators].
AB  - The paper contains current data on the different ways of the liver regeneration.
      There is still not enough data about control of the regeneration processes in the
      liver. However nuclear phosphatidylinositols and sphingomyelins have been shown
      to play a potent role of messengers signaling. The lipid messengers may be potent
      factors affecting process of liver regeneration after partial hepatectomy.

PMID- 11987491
TI  - [Proteases of neutrophilic granulocytes].
AB  - The literature referring to proteolytic enzymes of neutrophilic granulocytes was
      surveyed. Biosynthesis, subcellular distribution, division according to the
      catalytic site structure, inhibitors and methods used to determine the activity
      of these enzymes were discussed. The survey included metaloproteases
      (granulocytic collagenase, gelatinase B), serine proteases (granulocytic
      elastase, cathepsin G, protease 3), membraneous proteases (aminopeptidase N,
      aminopeptidase P, neprilisine), cysteine and aspartic cathepsins. The role of
      these proteases in the pathology and diagnostics of certain diseases was
      considered.

PMID- 11987492
TI  - A multidimensional scaling analysis of tone discrimination ability in Cantonese
      speaking children using a cochlear implant.
AB  - Tone discrimination testing with two groups of profoundly hearing-impaired
      children using a cochlear implant and one group of normally hearing children
      suggests that pitch level is perceptually more salient than pitch contour. In
      this paper, the discrimination results from these children are submitted to a
      multidimensional scaling analysis to determine what differences if any exist
      between the children in the information they use to discriminate between tone
      types. Through the multidimensional scaling analysis it is shown that, 'average
      pitch height' and 'pitch direction' are the most salient acoustic features in
      tone with pitch height being perceptually more important than pitch level.
      Furthermore, these acoustic features are similarly salient for all three groups
      of children despite differences in the source of auditory information and
      linguistic experience. Finally, the two groups of cochlear implant users who
      employ different speech processing strategies with their implant are shown to be
      distinguishable by differences in the relative salience of pitch direction.

PMID- 11987493
TI  - Markedness and the grammar in lexical diffusion of fricatives.
AB  - This paper examines the contributions of markedness and a child's grammar to the
      process of lexical diffusion in phonological acquisition. Archival data from 19
      preschoolers with functional phonological delays were submitted to descriptive
      analyses of productive sound change in fricatives. Children's presenting
      fricative inventory, the fricatives newly learned, and their position of
      occurrence were varied, with word frequency and neighbourhood density measured.
      Results indicated that lexical diffusion of fricatives occurred differentially by
      word position. Positional, featural and structural markedness further converged
      such that change in unmarked structure of any type was implemented in low
      frequency words. A child's presenting fricative inventory was not directly
      affiliated with systematic patterns of diffusion. These results have clinical
      applications for the evaluation of productive sound change and theoretical
      implications for deterministic models of lexical diffusion and processing models
      of word recognition.

PMID- 11987494
TI  - Comparison of methods in speech acquisition research.
AB  - The paper examines the effect of choices involved in speech acquisition research
      among children with impaired hearing. Choices involving transcription method,
      sampling procedures, subject selection and statistical approaches affect the
      outcome of any research. Two recent papers used different methodological
      approaches to examine the conversational speech samples of children with impaired
      hearing and arrived at differing conclusions about their rates of improvement. To
      compare these results, a further data set was examined using both methodologies.
      The analyses indicated a closer alignment of results than was immediately obvious
      from the two previous studies, suggesting that the different results were
      primarily due to differences in methodology.

PMID- 11987495
TI  - Tone discrimination in Cantonese-speaking children using a cochlear implant.
AB  - Most tone perception tests for Cantonese-speaking cochlear implant users have
      been based on tone identification tasks which require significant cognitive
      development to be successfully completed. Results from such tests suggest that
      cochlear implant child users are performing at about chance level and may not be
      receiving much information about pitch using the implant. This paper reports on
      the ability of cochlear implant child users to discriminate pitch variations in
      Cantonese by using an experimental procedure based on play audiometry. As part of
      the study, the usefulness of higher rates of electrode stimulation for aiding
      tone discrimination is also examined. Cochlear implant users are shown to derive
      sufficient information about pitch to discriminate most tone contrasts relatively
      successfully, with performance being most variable for contrasts involving tones
      clustered in the lower register of the speaker's fundamental frequency range.
      Contrary to hypothesis, higher electrode stimulation rates are not found to offer
      significant benefits for aiding pitch discrimination.

PMID- 11987496
TI  - [Skin disorders and job fitness assessment].
AB  - BACKGROUND: Assessment of fitness for employment represents the final phase of
      the risk evaluation and health surveillance carried out during pre-employment and
      periodical medical examination. Dermatoses are frequent diseases both in the
      general population and workers, therefore job fitness assessment for workers with
      skin problems will frequently fall within the occupational health area. The
      physician must verify whether or not the dermatosis is an occupational disease
      and must adopt preventive measures to avoid any worsening or relapse of the
      clinical situation due to occupational factors. OBJECTIVES: This article gives
      suggestions for correct management of occupational and non-occupational skin
      diseases in the workplace, with practical examples of job fitness assessment.
      METHODS: We first examined the role of the occupational physician in the
      evaluation of occupational risk factors that can induce work-related dermatoses
      or aggravate other dermatoses. We then discussed the factors that must be
      considered during assessment of fitness for employment when dermatoses are
      present. Finally, we examined practical examples of occupational or non
      occupational dermatoses that can cause functional limitations, factors that can
      influence job fitness evaluation, and the possible role of allergological tests.
      RESULTS AND CONCLUSIONS: Several dermatoses can be aggravated or caused by
      occupational factors (e.g. atopic dermatitis, allergic contact dermatitis,
      irritant contact dermatitis, keratinization disorders, lichen planus, physical
      urticaria). Close cooperation between the dermatologist and the occupational
      physician is very important in order to make an etiological diagnosis that is
      necessary for the job fitness assessment. It is difficult to define definitive
      criteria for the assessment of fitness for employment; in this article only some
      suggestions are made and they can vary according to the different situations.

PMID- 11987497
TI  - [Hearing disability in relation to audiometric threshold values: hypothesis on
      the determination of the onset of hearing loss].
AB  - BACKGROUND: The term auditory disability (AD) means the presence of auditory
      symptoms due to hearing loss. Until now the audiometric threshold cut-off between
      the presence or absence of AD was not clear. OBJECTIVES: In this study we
      attempted to define the value of audiometric threshold that could be considered
      as the limit between the presence or absence of weakness of auditory function,
      considered as the threshold as the 95th percentile of subjects that did not
      report AD. METHODS: The study group consisted of 1641 males, 891 normally hearing
      and 750 affected by noise-induced hearing loss (NIHL) Each subject was submitted
      to a questionnaire specifically created in order to determine the presence of AD.
      RESULTS: Statistical analysis confirmed the reliability of answers to items. AD
      was present in 577 subjects, not all affected by NIHL. Audiometric threshold and
      age correlated significatively with the degree of AD. CONCLUSIONS: The results
      obtained allowed the audiometric threshold values to be determined at the 95th
      percentile of subjects who did not report AD, in relation to the average of
      frequencies normally used in hearing loss evaluation.

PMID- 11987498
TI  - [Bronchial hyperreactivity to methacholine in a group of bakers sensitized to
      wheat flour].
AB  - BACKGROUND: Bakers' allergic diseases are a well known occurrence. Wheat flour is
      the most important allergen responsible for rhinoconjunctivitis and IgE mediated
      asthma. The good correlation between atopy, wheat flour sensitization and
      allergic diseases is also well known. In a previous study we described the
      results concerning sensitivity to wheat flour in a group of 300 bakers, followed
      up for 8 years. In this study we showed that the same subjects who were sensitive
      to wheat flour had no symptoms. AIM: The aim of this study was to carry out the
      metacholine test for bronchial hyperreactivity in a group of 14 bakers selected
      from the group of 300 previously studied. METHODS: The subjects underwent:
      pulmonary function test, IgE test, skin prick test with grass pollen,
      Dermatophagoides farinae, Dermatophagoides pteronissinus, wheat flour, and the
      metacholine test. RESULTS: The results of the metacholine test showed only one
      positive case in a subject with positive skin prick test. This agreed with the
      assumptions of our previous study that showed a sensitization (10%) to wheat
      flour but a low prevalence of allergic symptoms. CONCLUSIONS: Limited to the
      subjects studied, the results indicate an absence of a relationship between
      positive prick tests and aspecific bronchial hyperreactivity. Recent research
      that suggest a probable different genetic control of atopy, bronchial
      hyperreactivity and asthma is discussed. In our opinion effective primary and
      secondary prevention could account for this absence of relationship.

PMID- 11987499
TI  - [Acute poisoning with carbon dioxide: report of 2 fatal cases].
AB  - BACKGROUND: Carbon dioxide (CO2), a very high density gas, tends to stratify at
      the lowest levels of the atmosphere. It can be produced by neutral geothermal
      emissions, fermentative processes or by human and industrial activity. When
      carbon dioxide concentrations rise to a very high level in a confined and poorly
      ventilated space, the anoxic hazard is a very important cause of severe accidents
      that can involve workers and rescuers. At CO2 levels higher than 20% there is a
      very high risk of a fatal accident, also considering the odourless feature of
      this gas. OBJECT: Two fatal accidents in workers are described which occurred
      during inspection of a concrete well, built as a part of sewerage network in a
      rural area. In the weeks after the accident, composition and concentration of
      gases inside the well were analysed. We also considered the influence of an
      organic fertilizer called "pollina" which was found on the ground around the
      concrete well, in order to ascertain whether fermentation could alter the gas
      composition inside the well. METHODS: Samples of air and water were collected in
      the well and samples of the organic fertilizer (pollina) on the ground
      surrounding the concrete well were also taken. Different quantities of organic
      fertilizer (pollina) with or without water were incubated in airtight glass
      bottles and placed in a dark room at 20 degrees C temperature; analysis of air
      inside the glass bottles was performed after 7 and 18 days of incubation. All the
      samples of air and water were analysed by gas-chromatographic-mass-spectrometry.
      RESULTS: Analysis of the air samples collected inside the well after 2, 16 and 18
      weeks after the accident showed a low concentration of O2 (range 4.2-9%), a high
      concentration of CO2 (range 5.9-12.3%), a normal level of N2 (range 78-85%) and a
      concentration of N2O between 0.03 and 0.19%. In water collected 2 weeks after the
      accident at the bottom of the concrete well, CO2 and N2O concentrations of
      respectively 222 mg/L and 2 mg/L were measured. In the bottles with "pollina" we
      found, at different times of incubation, high concentrations of CO2 (highest
      value 25.2%), low levels of O2 (lowest value 0.5%) and negligible concentrations
      of N2O (< 0.015%). CONCLUSIONS: All these findings suggest that the atmosphere
      inside the concrete well was altered by the fermentative processes of pollina.
      The death of the two workers, caused by a poorly oxygenated atmosphere with a
      high concentration of carbon dioxide, can be classified under the confined space
      hypoxic syndrome (CSHS).

PMID- 11987500
TI  - [Degree of hepatitis C infection risk in the health care setting].
AB  - BACKGROUND: Hepatitis C virus is the most important aetiologic agent for non A
      non B hepatitis. The study of the prevalence of hepatitis C in health care
      workers is of primary interest because of the possible chronic evolution and the
      risk of cirrhosis and liver cancer. OBJECTIVES: The purpose of this study was to
      determine the prevalence of HCV among health care workers in 5 main hospitals and
      local health units in Turin and analyze the influence of occupational and non
      occupational risk factors. METHODS: Health care personnel were administered
      anonymous questionnaires and testing for anti-HCV antibody was performed.
      RESULTS: Prevalence rates in 4517 health care workers was 1.97%; the prevalence
      was higher in elderly workers (> 45 years) than in younger ones. The risk
      analysis did not reveal any significant correlation between HCV seroconversion
      and accidental blood exposure. However, a significant correlation was found with
      non-occupational risk factors. Unapparent infection was an unimportant risk
      factor for seroconversion. CONCLUSIONS: Hepatitis C prevalence in the population
      under study was comparable to that found in the general population. These results
      point to the need to reconsider the assumption that there is an increase of risk
      of seroconversion for health-care workers, in the absence of any occupational
      accidental exposure to hepatitis C virus.

PMID- 11987501
TI  - [Suspected glutaraldehyde poisoning: a case report].
AB  - AIMS: To report a case of anxiety, possibly due to glutaraldehyde poisoning in a
      female anaesthesiologist working in an operating room and exposed to 2% solution
      of glutaraldehyde, the only chemical used for disinfection of flexible endoscopic
      instruments. METHODS: A clinical evaluation was made and neurobehavioural
      functions were explored by sensitive neuropsychological testing: testing included
      a simple and complex reaction time and examination of the autonomic nervous
      system. The atmospheric concentration of glutaraldehyde was measured by means of
      a Bruel & Kjaer Multigas Monitor type 1302 analyzer. RESULTS: Adverse
      neurobehavioural effects, including headache, loss of attention, dizziness,
      anxiety, drowsiness on the job, alteration of homeostatic reflexes, were
      observed, and sensitive neuropsychological testing confirmed neurobehavioural
      impairment. No blood alterations related to exposure were found. Very high levels
      of glutaraldehyde were detected in the operating theatre. After ten days away
      from exposure to glutaraldehyde no symptoms and no behavioral effects on the
      central and autonomic nervous systems were detectable. CONCLUSIONS: Although
      conclusions cannot be drawn from a single case, exposure to a high level of
      glutaraldehyde, subjective symptoms, alteration of neurobehavioural performance,
      no consumption of CNS medication, no neurological or psychiatric disorders, no
      coffee consumption and alcohol intake, no exposure to other neurotoxic agents,
      complete recovery after removal from exposure to glutaraldehyde, are indicative
      of glutaraldehyde poisoning.

PMID- 11987502
TI  - [Manual weight carrying and fitness assessment].

PMID- 11987503
TI  - [Lost occupational tumors and their compensation: good news].

PMID- 11987504
TI  - [Competent physicians and basic physicians: a collaboration to reinitiate].

PMID- 11987505
TI  - [At the meeting of epidemiologists, an assessment of electromagnetic fields].

PMID- 11987506
TI  - Unanswered questions raised by antenatal diagnosis of renal and urinary tract
      abnormalities.

PMID- 11987507
TI  - [Aggression to the immature kidney].
AB  - The main causes for acute renal failure (ARF) in the newborn include endogenous
      factors (such as hypotension, hypovolemia, hypoxemia, perinatal asphyxia, and
      neonatal septicemia) and exogenous factors such as mechanical ventilation,
      nephrotoxic agents (antibiotics, indomethacin, ibuprofen, angiotensin converting
      enzyme inhibitors, and tolazoline). These conditions determinate vasoactive
      disturbances interfering with the delicate balance of intrarenal vasoconstrictor
      and vasodilator forces, which regulates the glomerular filtration rate (GFR) in
      the healthy term, and particularly in the premature infant. Factors influencing
      renal prognosis are the severity of the underlying disorder, the rapidity of an
      accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic
      complications. Plasma creatinine concentrations should be used with some caution
      for ARF diagnosis in the first days of life. General measures of kidney
      protection include correcting abnormalities in fluid homeostasis, adequate
      ventilation and rational choice of drugs. Moreover, in order to protect the
      kidney, different compounds have been proposed such as diuretics (furosemide and
      torasemide), and dopaminergic agents (dopamine, dopexamine). With the increasing
      knowledge of the mechanisms governing the development of ARF, progress has been
      made in the development of new treatment modalities. For example theophylline,
      calcium antagonists, ATP-MgCl2, thyroxine, and antibodies against endothelin may
      in the near future be used to prevent or ameliorate the prognosis of the neonatal
      stressed kidney. The main renal replacement therapies are possible in the
      newborn. However preventive measures are easily available in the neonatal period
      and they often represent the most efficacious procedures.

PMID- 11987508
TI  - Neonatal hypercalcemia.

PMID- 11987509
TI  - Urinary tract infections in the newborn.

PMID- 11987510
TI  - Asymptomatic bacteriuria.

PMID- 11987511
TI  - Laboratory management of neonatal sepsis and urinary tract infections: new
      perspectives.

PMID- 11987512
TI  - Diagnostic role of ultrasounds in urinary tract infections.

PMID- 11987513
TI  - Severe bilateral vesico-ureteric reflux.

PMID- 11987514
TI  - Hereditary renal cystic diseases.

PMID- 11987515
TI  - Hypertension: epidemiology and clinical approach.

PMID- 11987516
TI  - Genetics and nephro-uropathies.

PMID- 11987517
TI  - Endoscopic treatment of vesico-ureteral reflux and urinary incontinence.

PMID- 11987518
TI  - Dysfunctional voiding.
AB  - Wetting may be considered the Cinderella of paediatric medicine. Before
      discussing dysfunctional voiding, the milestones of the normal development of
      continence in the child and the definitions used to describe this topic are
      presented. Bladder storage requires (1): accommodation of increasing volumes of
      urine at low intravesical pressure and with appropriate sensation; (2): a bladder
      outlet that is closed and not modified during increase in intra-abdominal
      pressure; (3): absence of involuntary bladder contractions. Development of
      continence in the child involves three independent factors maturing
      concomitantly: (1) development of normal bladder capacity; (2) maturation of
      urethral sphincter function; (3) development of neural control over bladder
      sphincter function. All these processes are discussed. Abnormalities of any of
      these maturational sequences, which run parallel and overlapping, may result in
      clinically evident abnormalities of bladder sphincter control. Although
      dysfunctional voiding (DV) in children is very common its prevalence has not been
      well studied and, to date, and its origin is not well known. In a correct
      evaluation of functional voiding we must take into account different elements:
      the bladder capacity (that increases during the first 8 years of life roughly 30
      ml per year), the micturition frequency, post-void residual volumes, bladder
      dynamics, urinary flow rates. Thus the correct assessment of children with lower
      urinary tract dysfunction should include a detailed history. Signs of DV range
      from urge syndrome to complex incontinence patterns during the day and the night.
      In addition to incontinence problems, children may have frequency, urgency,
      straining to void, weak or interrupted urinary stream, urinary tract infections
      (UTIs) and chronic constipation with or without encopresis. DV are also referred
      in enuretic children who wet the bed more than one time per night and have a
      functional bladder capacity lower than attended for age. Recently standardisation
      and definitions of children's lower urinary tract dysfunction have been approved
      by International Children's continence Society (ICCS). The ICSS distinguishes
      between urinary incontinence, stress incontinence, overflow incontinence and urge
      syndrome. Clinical suggestions are presented for the daily practice.

PMID- 11987519
TI  - Proteinuria.

PMID- 11987520
TI  - Streptococcal tonsillitis and kidney impact.

PMID- 11987521
TI  - Epidemiology of glomerulonephritis.

PMID- 11987522
TI  - Diagnosis and treatment of glomerulonephritis.

PMID- 11987523
TI  - Drug misadventuring in neonatal nephrology.
AB  - Drug-related problems are associated with significant morbidity and mortality.
      Numerous factors contribute to the development of drug-related problems. These
      factors may be patient-dependent, such as the patient's degree of organ function
      and/or dysfunction, and underlying disease states. On the contrary the factors
      may depend on the specific drug and its pharmacokinetic parameters. Recently it
      has been also demonstrated the importance of genetic factors. Drug-related
      problems include a wide range of situations including the so-called drug
      misadventuring: adverse drug reaction (ADR), adverse drug event (ADE), drug
      induced disorder (DID), adverse drug experience (ADEexp). Certain drug classes
      are commonly associated with drug-induced disorders. Antibiotics and
      chemotherapeutic agents are responsible for approximately 30 percent of all
      adverse reactions. By an epidemiologic point of view between 3% and 11% of
      hospital admissions could be attributed to drug-related problems. Drug-induced
      disorders have historically been classified as predictable (Type A) or
      unpredictable (Type B) toxicity. Thus, a substantial portion of drug-induced
      disorders are predictable and potentially avoidable The kidney is vulnerable to
      drugs because of its high blood flow and large capillary surface area, its role
      as the excretory route for many drugs and its detoxifying action. Drug-induced
      acute renal failure accounts for 20% of total cases of acute renal failure in
      adult patients. Little is known about epidemiology of drug-induced disorders,
      especially in the pediatric kidney. Systematic epidemiological data on the
      incidence of drug-induced acute renal failure in newborn are not available.
      However, an increase in the last 10 years, in the involvement of drugs in acute
      renal failure has been observed in newborns. In the past it was suggested that
      drug-induced kidney damage (especially tht caused by aminoglycosides or
      glycopeptides) is less frequent and severe in newborns than in adults. However,
      this subject is controversial. Furthermore, it has recently been confirmed that
      low birth weights contribute to early onset of end stage renal disease. In view
      of the extremely widespread use of drugs in neonatology and the multiplicity of
      potential nephrotoxic factors, it is important to prevent iatrogenic effects. Ten
      rules for prevention of drug-induced nephrotoxicity are presented.

PMID- 11987524
TI  - Renal effects of antenatally or postnatally administered steroids.
AB  - Steroids administrated antenatally to the mothers improve postnatal outcomes of
      the newborns with pleiotropic effects. Furthermore steroids have been used in
      preterm infants to prevent or treat chronic lung disease. Synthetical
      glucocorticoids readily cross placental barrier and reach significant
      pharmacologic levels in the fetus: besides their well known pulmonary effects
      they have a concomitant maturational effect of postnatal renal function in
      preterm infants both with a direct and indirect effect. Endogenous and exogenous
      glucocorticoids play a role in the maintenance of glomerular filtration (GFR).
      The antenatal administration of steroids increases the GFR, in association to the
      maturation of the tubular function. According to different studies the
      improvement of renal function, expressed by the increase of GFR, is only
      partially referable to the increase of MAP and the improvement of the
      cardiovascular status, while it was imputable to a direct renal effect of the
      steroids, especially on the renal blood flow, on functional glomerular surface
      area available for filtration and on the glomerular filtrate of the single
      cortical nephron. However debate remains about the mechanism through which
      steroids would act on the renal vascular smooth muscolature. The increase the GFR
      observed after the antenatal administration of glucocorticoids in premature
      fetuses is also accompanied by an increase of urinary flow and of fractional
      excretion of sodium. Glucocorticoids would increase the proximal reabsorption of
      sodium increasing directly the function and the expression of the sodium
      transporters and both indirectly and directly increasing the activity of Na-K
      ATPase. In extremely low weight antenatal administration of betamethasone or
      dexamethasone was associated with lower estimated insensible water loss,
      secondary to a direct maturational effect in the skin epithelial barrier, as well
      as an increased reabsorption of the fetal lung fluid. Moreover antenatal
      glucocorticoid administration was associated, at birth, to a significant
      suppression of plasma renin activity and angiotensin II in comparison to the
      controls. Despite the wide use of the steroidal therapy in the prevention of the
      bronchopulmonary dysplasia, only few articles, in literature, analyse the effects
      of glucocorticoids on postnatal renal function, such as the increase in urinary
      flow. The authors think that steroids contribute in a meaningful way to the
      clinical improvement observed in children with BPD through the maturative action
      on the premature kidney with effect both at glomerular and tubular level.

PMID- 11987525
TI  - Bioethics in perinatal nephro-urology.

PMID- 11987526
TI  - Progress in perinatal nephro-urology.

PMID- 11987527
TI  - Obstructive uropathy: state of the art.

PMID- 11987528
TI  - Development of drugs in the newborn: impact on neonatal nephrology.

PMID- 11987529
TI  - [3-dimensional cephalometry in orthodontics. The current possibilities of Cepha
      3DT software].
AB  - A 3D cephalometric analysis method from a scanner acquisition, has been developed
      thanks to a long collaboration between the CIRAD modeling Laboratory and Jacques
      Treil. The model of skeletal description is based on eight landmarks related to
      the neuromatrical axis of facial growth (heads of the mallei, supraorbital,
      suborbital, submental points); it has been abundantly described. The purpose of
      this work consists in presenting the dentoalveolar level of the analysis. The
      description and the marking of the arches and the teeth mainly rest on the
      systematic use of a mathematical tool, the calculation of the central matrix of
      inertia, and on three fundamental choices: the identification of the dental
      arches from their constituting teeth leaving aside any alveolar marking, the
      marking of each tooth relative to the arch, as it can be observed by the
      orthodontist's eye, and not relative to the craniofacial architecture, the
      definition of the position of each tooth by the orientation of its
      coronoradicular axis and not its sole buccal side, Their uses in orthodontics are
      numerous: diagnosis, choice of the mechanics, therapeutic simulation, therapeutic
      follow up, analysis of the findings... Clinical applications illustrate the
      theoretical presentation.

PMID- 11987530
TI  - [The various families of composite adhesives: presentation and experimentation].
AB  - Today, manufacturers provide the orthodontist with a range of adhesive systems
      which is so wide that is often difficult for the orthodontist to make his choice
      between them. The adhesive systems fall into four categories: traditional
      hydrophobic bonding systems, hydrophilic bonding systems, self-etching bonding
      systems, resin-modified glass ionomer-cements. This article will attempt to
      examine the first three categories which correspond to those of the composite
      bonding systems. Following a presentation of bonding assembling and of the
      required specification of the bonding systems used in orthodontic practice, the
      three composite bonding systems will be examined along with their
      advantages/disadvantages before a closing description of the corresponding
      clinical protocol to be followed. Whenever one of our laboratory experiments
      enables us to provide experimental evidence, a presentation is made within the
      related chapters.

PMID- 11987531
TI  - [Growth and morphogenesis of the craniofacial bones. Applications in
      orthodontics. The concepts of J. Delaire].
AB  - The present report about J. Delaire's lecture summarizes his approach to: the
      nature and physiology of the membranous sutures, the "neural" and "adaptive"
      growth of the cranial base, the "central" and "cortical" development of the
      maxillary, the role of the premaxillary "skeletal entity" in the development of
      the anterior part of the face, the "bifocal" development of the mandible, the
      architectural balance of the craniofacial set (leading to the author's
      cephalometric analysis).

PMID- 11987532
TI  - [Orthodontic wires at the beginning of the 3rd millennium: innovation or
      improvement?].

PMID- 11987533
TI  - [Orthodontic wires at the beginning of the 3rd millennium: innovation or
      improvement?].

PMID- 11987534
TI  - [Corrosion and calculus. How can the wire/bracket slide mechanics be improved?].
AB  - Sliding mechanics are widely used in fixed orthodontic devices. Parasitic
      phenomena that block or slow the movement have, until now, been relatively
      neglected. The friction that appears at the interface of the
      wire/bracket/ligature opposes the free sliding action, necessary to allow the
      motor forces to displace the dental units that are guided on an appropriately
      shaped metal arch. There are three main causes that make unpredictable the
      control of orthodontic forces. The first one is the involuntary irregularities
      introduced onto the arches during their construction. The two others consist in
      factors blocking the sliding action. They can be unknown or misunderstood: the
      superficial corrosion of wires and brackets which affect the polished surface,
      and the appearance of adherent concretions due to hard and adherent tartar. This
      paper will discuss their involvement and describe the ways to improve the sliding
      effects.

PMID- 11987535
TI  - [Fetal ventilation and craniomaxillary development].
AB  - Data acquired by means of color Doppler ultrasound very explicitly suggest what
      the role of the fetal ventilation and nasal capsules in the morphogenesis of the
      maxillary prognathism, turbinates, nasal valves and nasopharynx could be.
      Furthermore, the dysmorphologies observed in Apert or Crouzon craniosynostosis,
      achondroplasia or unilateral cleft lip would also testify that the influence of
      the fetal ventilatory dynamics goes beyond the limits of the face and extends to
      the cranial base and the cranium. The wealth of raised hypothesis thanks to the
      contribution of this imaging system could question the validity of some
      conceptions of the fetal craniomaxillary morphogenesis.

PMID- 11987536
TI  - Human lens epithelial cell culture.

PMID- 11987537
TI  - An in vitro model of differentiated human airway epithelia. Methods for
      establishing primary cultures.

PMID- 11987538
TI  - Primary mouse keratinocyte culture.

PMID- 11987539
TI  - Analyzing apoptosis in cultured epithelial cells.

PMID- 11987540
TI  - Keratins as markers of epithelial cells.

PMID- 11987541
TI  - Epithelial cell integrins.

PMID- 11987542
TI  - Rat gastric mucosal epithelial cell culture.

PMID- 11987543
TI  - Isolation, cultivation, and differentiation of normal human epidermal
      keratinocytes in serum-free medium.

PMID- 11987544
TI  - Clinical application of autologous cultured epithelia for the treatment of burns
      and disfigurement of skin surfaces.

PMID- 11987545
TI  - Transplantation of cultured epithelial cells.

PMID- 11987546
TI  - An outgrowth culture system of normal human epithelium. An in vitro model to
      study the coordination of cellular migration and proliferation.

PMID- 11987547
TI  - Application of epithelial cell culture in drug transport in the respiratory
      tract.

PMID- 11987548
TI  - Applications of epithelial cell culture in studies of drug transport.

PMID- 11987549
TI  - Thymic epithelial cell culture.

PMID- 11987550
TI  - X-ray microanalysis of epithelial cells in culture.

PMID- 11987551
TI  - ENU mutagenesis of rat mammary epithelial cells.

PMID- 11987552
TI  - ENU-induced ovarian cancer.

PMID- 11987553
TI  - Measurement of membrane capacitance in epithelial monolayers.

PMID- 11987554
TI  - Assessing epithelial cell confluence by spectroscopy.

PMID- 11987555
TI  - Co-cultivation of liver epithelial cells with hepatocytes.

PMID- 11987556
TI  - Co-culture and crosstalk between endothelial cells and vascular smooth muscle
      cells mediated by intracellular calcium.

PMID- 11987557
TI  - Establishing epithelial-immune cell co-cultures. Effects on epithelial ion
      transport and permeability.

PMID- 11987558
TI  - Bile duct epithelial cell culture.

PMID- 11987559
TI  - Explant cultures of embryonic epithelium. Analysis of mesenchymal signals.

PMID- 11987560
TI  - Bacterial interactions with host epithelium in vitro.

PMID- 11987561
TI  - Liver epithelial cell culture.

PMID- 11987562
TI  - Pulmonary epithelial cell culture.

PMID- 11987563
TI  - Human airway epithelial cell culture.

PMID- 11987564
TI  - Prostate epithelial cell isolation and culture.

PMID- 11987565
TI  - A bovine mammary endothelial/epithelial cell culture model of the blood/milk
      barrier.

PMID- 11987566
TI  - The blood-CSF barrier in culture. Development of a primary culture and
      transepithelial transport model from choroidal epithelial cells.

PMID- 11987567
TI  - [Fetal monitoring during labor using cardiotocography and ST analysis of the
      fetal electrocardiogram--preliminary report].

PMID- 11987568
TI  - [Long-term results of retropubic vesicopexy in the treatment of urinary stress
      incontinence in women].
AB  - OBJECTIVE: To evaluate long-term results of retropubic vesicopexy (e.g. direct
      suspension of the anterior and lateral walls of the bladder base) in the
      treatment of female stress urinary incontinence (SUI) caused by hypermobile
      urethra. DESIGN: Retrospective clinical study. SETTING: Department of Urology,
      Faculty of Medicine, University of P. J. Safarik, Kosice, Slovakia. METHODS: From
      a total of 44 females operated on between 1985-1992, 41 (93%) were available for
      the study (mean age 50 years, 28 pure SUI, 13 mixed incontinence). 18 (44%)
      patients had failed previous incontinence surgery. Based on the data collected by
      a detailed questionnaire as a success cure and/or significant improvement (max. 1
      pad/day) of SUI have been considered. RESULTS: With a mean of 103 month follow-up
      period (48-160 months), 32 (78%) patients reported to have their SUI cured,
      another 5 (12%) significantly improved. Both persistent (8/13, 62%) and de novo
      urge incontinence (5/28, 18%) have shown to the main reasons for "partial"
      satisfaction only with the outcome of surgery. Perioperative bleeding requiring
      blood transfusion was the only serious complication met with this procedure (2
      patients). CONCLUSION: Long-term results of vesicopexy is comparable with the
      effect of standard retropubic procedures like Burch colposuspension or MMK
      urethropexy. Technical simplicity, no risk of osteitis pubis as well as
      persisting micturition problems may be considered the main advantages of the
      procedure. Because of lower cure rate the procedure is less suitable for SUI type
      IIB.

PMID- 11987569
TI  - [Hormone replacement therapy and ovarian tumors].
AB  - OBJECTIVE: Analysis of risk and protective factors and hormone replacement
      therapy in the aethiology and pathogenesis of ovarian cancer. The role of hormone
      replacement therapy in the complex treatment in women with ovarian cancer is
      discussed. DESIGN: Reviewed article. SETTING: Department of Obstetrics and
      Gynaecology, University Hospital Ostrava. METHODS: Analysis of epidemiological
      studies. CONCLUSION: The role of hormone replacement therapy as a risk factor of
      ovarian cancer has not been confirmed. Hormone replacement therapy as a part of
      supportive and symptomatic therapy has been acceptable in a great deal of
      patients with ovarian cancer.

PMID- 11987570
TI  - [Prediction of premature labor--multifactorial analysis of a prospective clinical
      study].
AB  - OBJECTIVE: To evaluate, which of selected anamnestic, laboratory and
      ultrasonographic (USG) parameters could contribute to the prediction of
      prematurity. DESIGN: Prospective, observational, clinical study. SETTING:
      Department of Obstetrics and Gynecology, 1st Faculty of Medicine and the General
      Faculty Hospital, Charles University, Prague. METHODS: 349 women with the
      singleton pregnancy were followed from the half of the 2nd trimester until the
      end of gestation. At each woman the anamnestic (age, parity, pregravid BMI,
      weight gain until 20th week, significant risk from patient's history, cigarette
      smoking, risk pregnancy symptoms until 20th week), laboratory (maternal serum
      concentration of AFP, hCG, and uE3/triple test/at 16th week, the blood count and
      ferritin concentration at 18th-20th week, bacteriological cultivation of the
      smear from the cervix at 34th-36th week), and USG (transvaginal cervicometry and
      doppler flowmetry of the uterine arteries at 18th-20th week) data were
      established. With the aid of one-dimensional and multi-dimensional analysis the
      dependence of completed gestational age and preterm delivery (before completed
      37th week) on above mentioned parameters was tested. RESULTS: 314 women completed
      the study. We proved a significant dependence of prematurity on the following
      markers: risk pregnancy symptoms until 20th week (RR 2.94), abnormal triple test
      (RR 4.63), cultivation of pathogens from the cervix (RR 5.49), USG established
      cervical length (P < 0.0001), abnormal result of cervicometry (RR 19.02), both
      doppler parameters (RI of uterine arteries: P < 0.0001; presence of early
      diastolic notch: RR 2.84). The results of multi-dimensional analysis confirmed
      superiority of USG cervicometry in prediction of both measured outcomes.
      CONCLUSION: The predictive value of some of selected anamnestic, laboratory, and
      USG markers of premature delivery was proved at random population of women with
      singleton pregnancy. The abnormal result of transvaginal USG cervicometry was the
      most significant predictor of prematurity. We recommend a routine performing of
      cervicometry (as a part of USG screening at 18th-20th week) for early selection
      of women with significantly increased risk of prematurity.

PMID- 11987571
TI  - [Perception of changes in body weight during pregnancy].
AB  - ELSPAC (European Longitudinal Study of Pregnancy and Childhood) includes in Czech
      Republic the set of pregnant women who have their permanent address in Brno and
      Znojmo district with the term of the delivery between March 1991 and June 1992.
      OBJECTIVE: Wide and repeated anamnestic and clinical investigations of parents
      and children making possible prospective analyses pregnancy and development of
      child. DESIGN: Prospective study. SETTING: Research Institute of Child Health,
      Brno. METHODS: In the set of 7911 women, the relationship between subjective
      perception of weight and pregnancy in the first and second trimester was
      investigated. The data were obtained from two questionnaires filled by pregnant
      woman and obstetricians. RESULTS: In the whole set, 12% of women are concerned
      with their weight intensively and perception of their weight is rather negative.
      5.8% of women show negative relationship to pregnancy at the beginning, in the
      second trimester it is only the small fragment of all women. The reason for the
      negative perception of the weight is influenced by somatic, psychic and social
      aspects. The most important issue is emotional stability. The most common
      increase in weight was between 8-15 kg, in average 11.34 kg. The increase in
      weight in pregnancy is, among other reason, mediated by nutrition, smoking and
      job. CONCLUSION: Physical and psychical changes occur during the pregnancy. One
      of very evident changes is also increase in weight. The ability to accept this
      chance depends especially on emotional stability, food, smoking and job of
      pregnant women.

PMID- 11987572
TI  - [Premature fetal membrane rupture after amniocentesis in the second trimester and
      successful use of fibrin glue--case report].
AB  - OBJECTIVE: The aim of this study was to evaluate fibrin sealing in management of
      premature rupture of membranes after amniocentesis in early second trimester.
      DESIGN: Case report. SETTING: II. gynekologicko-porodnicka Klinika LFUK NsP
      Ruzinov, Bratislava; Department of Obstetrics and Gynecology, Spectrum Health-
      Blodgett Campus, Grand Rapids, USA. SUBJECT AND METHOD: In this case report
      authors report the use of fibrin sealant (Tissucol KIT, Immuno, A) in management
      of premature rupture of membranes after genetic amniocentesis. The sealing was
      performed in 19 + 0 week of pregnancy, 15 days after amniocentesis. The pregnancy
      was terminated by caesarean section in 34-th week, 98 days after sealing. The
      newborn was in stable condition, without clinical or laboratory signs of
      infection. No skeletal deformities or adverse effects of fibrin sealant were
      observed. Neurological examination in 3 month of age evaluates the
      psychomotorical development as normal. CONCLUSION: We consider the perinatal
      outcome of this pregnancy as positive.

PMID- 11987573
TI  - [Risks in hysteroscopy in patients with endometrial carcinoma--a prospective
      clinical study].
AB  - OBJECTIVE: The evaluation of the risk of hysteroscopy (HSC) in patients with
      endometrial carcinoma with regard to the dissemination of disease and the
      deterioration of its prognosis. DESIGN: A prospective multicentric study.
      SETTING: Department of Obstetrics and Gynaecology and Institute of Pathology of
      the Palacky Univerzity Medical School and University Hospital, Olomouc;
      Obstetrical and Gynecological Departments of collaborating hospitals. METHODS:
      Two groups of patients with endometrial carcinoma were compared on the basis of
      cytological examinations from the peritoneal cavity. The study group (n = 156)
      consisted of patients whose diagnosis was made on the base of HSC and targeted
      biopsy. The control group (n = 71) included patients with the classical D&C. Both
      groups were comparable as to the distribution of clinical stages of the disease
      (P < 0.05). Cytological examinations were performed from the fluid obtained by
      the puncture of the cul de sac at the end of the HSC procedure and from the
      peritoneal lavage at the beginning of the following operation. Results of both
      groups were compared and statistically evaluated. RESULTS AND CONCLUSIONS: The
      comparison of the cytological findings from the punctures of the cul de sac after
      the HSC and from the lavages at the following operation did not show an increased
      penetration of malignant cells from the uterus into the abdominal cavity.
      Similarly, the comparison of cytological findings from the peritoneal lavages
      after HSC and probatory curettage did not show a statistically significant
      difference between both groups. We assume that HSC does not increase the risk of
      dissemination of tumour cells into the peritoneal cavity and does not deteriorate
      the prognosis of the disease.

PMID- 11987574
TI  - [Vulvar carcinoma--retrospective study of 47 cases (epidemiology, etiology and
      long-term results].
AB  - OBJECTIVE: To evaluate the incidence of vulvar carcinoma, epidemiological signs
      and therapeutic results in patients with vulvar malignancies during the stated
      time period. DESIGN: Retrospective clinical study. SETTING: Department of
      Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and
      General Faculty Hospital, Prague. METHOD: An analysis of the available clinical
      documentation of the patients of the oncological outpatient service of the
      Department of Obstetrics and Gynaecology. RESULTS: Vulvar carcinoma represents 4%
      of all malignant tumours of female genital tract. It concerns predominantly elder
      women (the average age is 74.2 years). The overall 5-year survival, with no
      regard to the stage of the disease, is 39.1% in our group. This low figure is due
      to the high age of the group and to the inappropriate therapeutic approach owed
      to the internal comorbidity, advanced age and the fact that the majority of cases
      are diagnosed in advanced stage. CONCLUSION: In spite of good access, the
      introduction of screening program is unlikely due to the age distribution,
      biological behaviour and difficulties in diagnostic of premalignant lesions. With
      regard to the increasing incidence of in situ carcinoma whose ethiopathogenesis
      is affected by HPV infection, it is necessary to pay more attention to vulva
      lesions in terms of an early histopathological verification. The treatment of the
      external genital tract malignancies should be concentrated to the centers with
      the greatest experience of their management.

PMID- 11987575
TI  - [Treatment of urinary stress incontinence in women with a periurethral implant].
AB  - OBJECTIVE: The aim of this article is the comprehensive information about
      different bulking substances and their use for the treatment of genuine stress
      urinary incontinence in women. DESIGN: The review summarizes various materials
      used for this purpose, methods of their application, possible complications and
      results of clinical studies of implants. SETTING: Department of Obstetrics and
      Gynaecology of Charles University and Faculty Hospital Bulovka takes part in the
      development of the new metacrylate of Czech origin. SUBJECT AND METHOD: Current
      scientific literature as listed in the article. CONCLUSION: Implants seem to be a
      useful alternative method in the treatment of the genuine stress incontinence in
      women.

PMID- 11987576
TI  - [Penetration of cervical mucus by native and cryopreserved sperm--the Kremer
      test].
AB  - OBJECTIVE: The penetration of native and cryopreserved human spermatozoa into
      cervical mucus--the Kremer's test. DESIGN: Retrospective study. SETTING:
      Department of Obstetrics and Gynaecology, Medical Faculty, Charles University and
      Faculty Hospital, Plzen. METHODS: Human cervical mucus was collected from 73
      women visiting the Division of immunology of reproduction, Department of
      Obstetrics and Gynaecology in Plzen. Native spermatozoa was obtained from the
      patients of the Division of Immunology of Reproduction as well. Cryopreserved
      only in its seminal plasma was obtained from the spermabank of our department.
      The distance of penetration in centimetres from the start was examined in inverse
      microscopy after 30, 60, 90 and 90 minutes. Also the character and duration of
      the sperm motility was analyzed. RESULTS: The penetration of native spermatozoa
      was higher than the penetration of cryopreserved spermatozoa in each case. The
      native spermatozoa had a higher penetrability, motility and life-ability.
      Spermatozoa preserved only in its seminal plasma had the parameters demonstrably
      lower. Nevertheless these spermatozoa can be successfully used for homologue or
      heterologue insemination or for IVF because these spermatozoa do not loose its
      enzymatic and remaining energetic equipment by penetration the cervical canal.
      CONCLUSION: The Kremer's test belongs to the reliable methods of penetration
      ability of native and cryopreserved sperms.

PMID- 11987577
TI  - [Inhibin in pregnancy--a new screening marker for prenatal diagnosis?].

PMID- 11987578
TI  - [Recommendations for the diagnosis and therapy of vulvovaginitis].

PMID- 11987579
TI  - [Effectiveness of influenza vaccination in healthy adults--a fourfold decrease in
      influenza morbidity during one influenza season].
AB  - INTRODUCTION: Despite the existence and availability of effective and safe
      influenza vaccines, influenza still remains an important cause of morbidity and
      mortality worldwide, incl. all economic consequences and the increased number of
      days of work incapacity. Vaccination against influenza is an effective method of
      prevention of the disease and its complications. Nevertheless many people still
      do not trust the effectiveness of anti-influenza vaccination, incl. many
      physicians, nurses and other health professionals. The objective of the present
      study is to evaluate the effectiveness of vaccination against influenza in
      healthy adults aged 18-60 years, vaccinated with one of the five commonly
      available vaccines. The evaluation is based on notifications of influenza and
      influenza--like diseases. METHOD: The trial comprised 375 subjects vaccinated
      against influenza during a given season, as a control group served 340 non
      vaccinated subjects. Both groups of volunteers were investigated for six months.
      During this period the incidence of influenza or influenza--like diseases was
      recorded, the presence of local and general influenza symptoms, the number of
      days of work incapacity and the number of visits to the doctor. These data were
      obtained by the postal correspondence method. RESULTS: In the group of 375
      vaccinated subjects 17 (4.5%) became ill. In the group of non-vaccinated subjects
      65 (19.1%) became ill. The difference in the incidence of influenza was
      statistically significant. In subjects vaccinated against influenza a 73-76%
      effectiveness of vaccination was achieved. Subjects in the non-vaccinated group
      reported more than a fourfold incidence of influenza as compared with vaccinated
      subjects. The symptoms of the disease did not differ significantly in the two
      groups. The most frequent symptom of the disease which was recorded in both
      groups was fever higher than 38 degrees C, pain in the joints, myalgia and
      finally cough. More than two thirds of the sick volunteers visited their doctor
      while ill. CONCLUSION: From the results of the study it is obvious that
      vaccination against influenza in healthy adults significantly reduces the
      incidence of influenza, reduces the number of days of work incapacity and leads
      to a diminution of the number of medical examinations. Vaccination against
      influenza is effective in the prevention of the disease and is beneficial also
      for healthy non-risk population groups.

PMID- 11987580
TI  - [Spoligotypes of Mycobacterium tuberculosis in the Czech population (methods and
      pilot study)].
AB  - In the introduction the authors describe molecular genetic principles of spacer
      oligonucleotide typing of the M. tuberculosis complex and mention in detail the
      methodical procedure of implementation of this examination technique incl.
      computer analysis of results. In the pilot part of the study the authors describe
      examination of 71 strains of M. tuberculosis isolated from patients living in the
      capital of Prague and 37 strains from patients in the South Moravian region of
      the Czech Republic. In the group of Prague strains a total of 7 clusters was
      identified formed by 2-14 identical profiles of spoligotypes and 37 individually
      different profiles. In the South Moravian strains there were 6 clusters with 2-14
      identical spoligotypes and 10 non-clustered profiles. In neither of the groups
      there were spoligotypes typical for the genetic family Beijing or Africa. The
      study is a preliminary molecular epidemiological analysis where DNA fingerprint
      RFLP profiles are compared with spoligotypes of strains of M. tuberculosis of
      patients from the capital of Prague and the South Moravian region of the Czech
      Republic.

PMID- 11987581
TI  - [Lyme borreliosis--incidence of serum anti-myelin antibodies].
AB  - The method of enzyme immunoassay (ELISA) was used for detection of antibodies
      against the basic protein myelin (antimyelin antibodies) for a group of serum
      samples (n 36) with positive anti-borrelia immunoglobulins IgG and IgM (ELISA
      Borrelia afzelii) and their immune complexes (ELISA-PEG). Antimyelin antibodies
      (ELISA-Doxa Kit-Myelin Basic Protein Antibodies) were assessed in 31% (n 11) of
      examined serum samples of patients with the working diagnosis of Lyme
      borreliosis. Statistical analysis (p 0.07) confirmed a more frequent incidence of
      antimyelin antibodies in younger female subjects (age 31 years) as compared with
      a group of sera (n 25) where the authors did not record the formation of
      immunoglobulins against the basic myelin protein (age 51 years). Neither the
      value of titres nor the frequency of detected anti-borrelia IgG and IgM and
      immune complexes did not differ significantly in the two groups. From the
      assembled results ensues that in the course of Lyme borreliosis, in chronic
      affection of organs an autoimmune reaction may develop where the basic myelin
      protein is damaged (demyelinizatio) and subsequently antimyelin antibodies are
      formed.

PMID- 11987582
TI  - [Evaluation of the effectiveness of the BACTEC MGIT automatic system for culture
      of mycobacteria in comparison with classical methods of culture. Experience after
      one year of use].
AB  - The fully automatic non-radiometric cultivation system BACTEC MGIT 960 of Becton
      Dickinson is one of the systems using the so-called rapid metabolic method of
      mycobacteria cultivation. For detection of mycobacterial growth it uses the
      fluorescent technology. The objective of the present work is to compare the
      effectiveness of this system with classical cultivation on solid (egg) and liquid
      media. During the period from April 27, 1999 till April 28, 2000 in our
      department concurrently by both methods a total of 2144 samples were examined
      from which a total of 149 mycobacterial strains were isolated. It was revealed
      that the BACTEC MGIT 960 system is much more sensitive than classical cultivation
      (it detected 136 isolates as compared with 103 detected by the classical method):
      in isolation of Mycobacterium the difference in sensitivity is even more marked
      (from the total number of isolated strains of Mycobacterium tuberculosis the
      BACTEC MGIT 960 detected 105, classical cultivation only 76). The mean Time to
      Detection (TTD) of positive samples in the BACTEC MGIT 960 system was 13.2 days
      while for classical cultivation it was 33.6 days. It was thus confirmed that the
      BACTEC MGIT 960 achieves, as compared with classical cultivation, better results
      which applies to the sensitivity of the two methods as well as to the detection
      rate of positive samples.

PMID- 11987583
TI  - [Epidemiology of dermatomycoses in Slovakia].
AB  - The authors analyze the incidence of dermatomycoses in the Slovak Republic in
      1994-1999. They found an increase of these infections in particular
      epidermophytoses, trichophytoses and candidoses. From 25,762 examined subjects
      with suspicion of dermatomycosis they isolated in 1990 till 1999 8,237 cultures
      of dermatophytes. The most frequent causal agent was Trichophyton rubrum
      (81.61%). In the conclusion the authors draw attention to the inevitability of
      introduction of effective preventive measures.

PMID- 11987584
TI  - [Serologic detection of hantavirus antibodies].
AB  - Within the framework of diagnosis of highly dangerous infections in the Army of
      the Czech Republic serological assessment of hantaviral antibodies was
      introduced. Because military units in the field can be in contact with sources of
      hantaviral infections, the authors investigated this population sample. In 1999
      2000 a total of 542 healthy subjects were examined (age 20-40 years). Hantaviral
      antibodies were detected in 9. In three antibodies against the serotype Hantaan
      were found, in two antibodies against serotype Puumala and in four against
      serotype Seoul. The mean seropositivity was 1.66%. As compared with results which
      were obtained in the National Institute of Public Health in Prague in 1998 in a
      sample of the general population (430 subjects) where seropositivity of
      hantaviral antibodies was 0.93% the seropositivity in military units is higher.
      It is thus essential to make this laboratory diagnosis in the laboratories of the
      Army of the Czech Republic.

PMID- 11987585
TI  - [Risk of fungal infection from foods, particularly in immunocompromised
      patients].
AB  - The aim of our study was the evaluation of fungal contamination of food
      distributed in hospitals to the immunocompromised patients. 97 samples of 10
      sorts of fruit, 100 samples of 17 sorts of cheeses and 56 samples of 11 sorts of
      smoked meat products were investigated by cultivation on Sabourand's agar at 25
      degrees C for 10 days. The yeasts (Candida, Trichosporon, Saccharomyces,
      Rhodotorula, Aureobasidium) were found in 82% of fruit, in 13% of cheeses and in
      46% of smoked meat products. The filamentous fungi (Cladosporium, Alternaria,
      Penicillium, Aspergillus, Mucor and Helminthosporium) were found on all samples
      of fruit, in 44% of cheeses and in 3% of smoked foods. Our results show that the
      fungal contamination of the investigated food is not negligible. The isolated
      strains are agents of candidoses, phaeohyphomycoses, mucormycoses and
      aspergilloses and can kill immunocompromised patients.

PMID- 11987588
TI  - Multicultural psychology: bringing together gender and ethnicity.
AB  - This article suggests that just as gender studies should not proceed without
      consideration of the various contexts in which men and women behave, similarly
      multicultural psychology should recognize gender, among other characteristics in
      the populations examined. Focusing on ethnic group women, who are understudied,
      develops this theme. Two arguments are proposed: (a) that gender must be
      recognized as impinging on every aspect of psychological research and practice,
      and (b) that gender should be considered an aspect of culture, just as ethnicity
      now is. The literature in psychology is reviewed to demonstrate how erroneous
      beliefs and exclusion operate to minimize examination of ethnicity and gender.
      Finally, a call to advocacy is made for attention to complexity.

PMID- 11987589
TI  - Sexual orientations in perspective.
AB  - This article presents a new paradigm for understanding the complexity of human
      sexual, affectional, and erotic attractions--commonly known as sexual
      orientation. This new paradigm recognizes that there is great diversity among
      sexual orientations, erotic and emotional attractions, behaviors, and identities
      and that there are complex interrelations among these dimensions. Sexual
      orientation is determined by multiple influences, including a wide range of
      sociocultural factors. The development of sexual orientation is arrived at
      through multiple pathways. Individuals with the same sexual orientation may have
      little else in common. Thus, a model of sexual orientation is presented that is
      based on multiplicity, not sameness, and that examines the overlapping identities
      and statuses of culture, gender, age, race, ethnicity, class, disability, and
      sexuality.

PMID- 11987590
TI  - Could you hold the door for me? Including disability in diversity.
AB  - This article is intended to help those unfamiliar with disability studies by
      providing a context for disability on which psychologists can build. The 1st part
      presents data on disability training in graduate clinical programs and on
      training accessibility for graduate students with disabilities. The 2nd part is
      an introduction to disability studies and includes 3 core concepts of disability
      issues in psychology: (a) the framing of disability from 3 models (the moral,
      medical, and social models); (b) the ways in which disability is like and unlike
      other minority groups; and (c) the language that is used to describe disability.
      These 2 parts taken together constitute a brief introduction to disability issues
      within psychology.

PMID- 11987591
TI  - Ethnic differences in clinical presentation of depression in adult women.
AB  - This study examined ethnic differences in self-report and interviewer-rated
      depressive symptoms and estimated the contributions of sociodemographic and
      psychosocial factors in predicting severity of depression. One hundred twenty
      five clinically depressed African American (n = 46), Caucasian (n = 36), and
      Latina (n = 43) women were recruited. After controlling for differences in
      socioeconomic status, African American women reported more symptoms of distress
      and Latinas were rated as significantly more depressed than the other groups.
      However, these ethnic differences were not moderated by either education or
      employment. Finally, hierarchical regression analysis indicated that severity of
      depression was predicted by low education, being single, being Latina, high
      perceived stress, and feelings of hopelessness. Additional research is needed to
      validate these results and to investigate their clinical significance.

PMID- 11987592
TI  - Racial identity and self-esteem among black Brazilian men: race matters in Brazil
      too!
AB  - The contribution of J. E. Helms's (1990) people of color racial identity model to
      the collective and individual self-esteem of Black Brazilian men (N = 203) was
      explored. The relationships between racial identity attitudes and other racial
      constructs such as skin color, racial group self-designation, and racial mistrust
      were also examined. Hierarchical regression analyses revealed that the set of
      racial identity attitudes (conformity, dissonance, resistance, and
      internalization) was significant in predicting self-esteem (collective and
      individual). Results from a multivariate analysis of variance showed an effect
      for skin color on racial attitudes. In addition, racial identity was
      significantly related to mistrust of Whites by Black Brazilian men. The
      implications of these findings are discussed in the context of racial relations
      in Brazil.

PMID- 11987593
TI  - Introduction: a report on the National Multicultural Conference and Summit II.
AB  - Multiculturalism, in its broadest terms, not only is defined by race and
      ethnicity but also involves topics of gender, sexual orientation, and disability.
      Underlying this notion is the assumption that there is no one way to
      conceptualize human behavior, no one theory that explains the realities and
      experiences of various forms of diversity, and no particular set of competencies
      that have been proven to be effective with every form of diversity. Yet, it is
      possible to seek and provide information that can move psychologists and other
      social scientists forward in the search for multicultural awareness, respect, and
      competence. The 2nd National Multicultural Conference and Summit, held in January
      2001 in Santa Barbara, California, was designed to promote knowledge about
      multiculturalism in these broad terms. This introduction to the special section
      is designed to (a) provide an overview of the proceedings of the Summit, (b)
      identify themes that emerged throughout the Summit with a special focus on the
      major keynote addresses, and (c) recommend future directions for education,
      training, practice, and research in multicultural psychology.

PMID- 11987594
TI  - Why can't we just get along? Interpersonal biases and interracial distrust.
AB  - The authors review a series of studies that illustrate how one form of
      contemporary racial bias of Whites, aversive racism, can shape different
      perspectives of Blacks and Whites in ways that can undermine race relations. This
      research demonstrates that contemporary racism among Whites is subtle, often
      unintentional, and unconscious but that its effects are systematically damaging
      to race relations by fostering miscommunication and distrust. In particular, the
      authors examine the effects of aversive racism on outcomes for Blacks (e.g., in
      selection decisions), on the ways that Whites behave in interracial interactions,
      in the impressions that Whites and Blacks form of each other in these
      interactions, and on the task efficiency of interracial dyads.

PMID- 11987595
TI  - [Papillary glioneuronal tumor].

PMID- 11987596
TI  - [Neoplasms of pineal parenchyma].

PMID- 11987597
TI  - [Medulloepithelioma].

PMID- 11987598
TI  - [Primitive neuroectodermal tumor].

PMID- 11987599
TI  - [Fibrillary astrocytoma].

PMID- 11987600
TI  - [Ependymoblastoma].

PMID- 11987601
TI  - [Atypical teratoid/rhabdoid tumor (AT/RT)].

PMID- 11987602
TI  - [Nerve sheath tumors of cranial and peripheral nerves].

PMID- 11987603
TI  - [Meningeal neoplasms].

PMID- 11987604
TI  - [Melanocytic tumors of the central nervous system (melanocytoma, melanoma
      malignum)].

PMID- 11987605
TI  - [Malignant lymphoma of the central nervous system (lymphoma malignum)].

PMID- 11987606
TI  - [Germ cell OUN tumors].

PMID- 11987607
TI  - [Congenital neoplasms].

PMID- 11987608
TI  - [Neoplasms in the vicinity of the sella].

PMID- 11987609
TI  - [Neuro-imaging for diagnosis of brain neoplasms in children].

PMID- 11987610
TI  - [Glioblastoma multiforme].

PMID- 11987611
TI  - [Pleomorphic xanthoastrocytoma].

PMID- 11987612
TI  - [Ependymomal neoplasms].

PMID- 11987613
TI  - [Plexus papilloma].

PMID- 11987614
TI  - [Polar spongioblastoma].

PMID- 11987615
TI  - [Brain gliomatosis].

PMID- 11987616
TI  - [Embryonal astroblastoma].

PMID- 11987617
TI  - [Gangliocytoma, ganglioglioma and anaplastic oligodendroglioma].

PMID- 11987618
TI  - [Central neurocytoma].

PMID- 11987619
TI  - [Infantile desmoplastic ganglioglioma and desmoplastic cerebral astrocytoma of
      infancy].

PMID- 11987621
TI  - One "A" you don't want your kids to get.

PMID- 11987620
TI  - [Dysembryoplastic neuroepithelial tumor].

PMID- 11987622
TI  - Lesbian, gay, and bisexual health.

PMID- 11987623
TI  - Imprint.

PMID- 11987624
TI  - Teen pregnancy prevention: new tool for school nurses.

PMID- 11987625
TI  - Mini resolutions to better health....

PMID- 11987626
TI  - EPA launches childhood asthma media campaign.

PMID- 11987627
TI  - Students, sun, safety.

PMID- 11987628
TI  - President Bush's "No Child Left Behind" plan.

PMID- 11987629
TI  - Bipolar illness and depression in children and teenagers.

PMID- 11987630
TI  - What would you do?

PMID- 11987631
TI  - Who ya gonna call? ...flex nurses!!!

PMID- 11987632
TI  - Biking safety in the summer.

PMID- 11987633
TI  - Don't let stress tax your health. Tips from the National Headache Foundation.

PMID- 11987634
TI  - Helping a child deal with death.

PMID- 11987635
TI  - Barriers to education: kids voice serious concerns.

PMID- 11987636
TI  - Successful 1st year for NASN-supported suicide prevention program: register your
      school now for next fall.

PMID- 11987638
TI  - As summer heats up, staying hydrated is essential (National Athletic Trainers'
      Association, April, 2000).

PMID- 11987637
TI  - NASN tracks school nurse population.

PMID- 11987639
TI  - Nurses rightfully are tired.

PMID- 11987640
TI  - The Code of Ethics for Nurses.

PMID- 11987641
TI  - Testimony making a difference.

PMID- 11987642
TI  - RNs speak out for their profession.

PMID- 11987643
TI  - When colon cancer runs in the family.

PMID- 11987644
TI  - Data to make a difference.

PMID- 11987645
TI  - Work conditions cause nurse shortage.

PMID- 11987646
TI  - Whistleblower protection.
AB  - The American Nurses Association's Code for Nurses states that "The nurse acts to
      safeguard the client and the public when health care and safety are affected by
      incompetent, unethical, or illegal practice by any person." In the interpretive
      statements which accompany the Code for Nurses, it is stated that "As an advocate
      for the client, the nurse must be alert to and take appropriate action regarding
      any instances of incompetent, unethical, or illegal practice by any member of the
      health care team or the health care system, or any action on the part of others
      that places the rights of best interests of the client in jeopardy." As of March
      of 2000, 22 states have whistleblower legislation introduced, 3 states had
      legislation enacted in the year 2000, and 10 states had legislation enacted in
      prior years. In a recent national survey of registered nurses, 56% of the nurses
      responding believed that their time available for direct patient care had
      decreased and 75% of those responding believed that the quality of nursing care
      had declined in their work setting during the last two years. Reasons for the
      declining care included: inadequate staffing, decreased nurse satisfaction, and a
      delay in providing basic care.

PMID- 11987647
TI  - Tobacco use as a public health issue.
AB  - Almost one-quarter of all adults are current smokers, along with more than a
      third of all high school students. Although a small drop in underage smoking from
      1997 to 1998 has interrupted the otherwise steady increases in youth smoking
      since the early 1990s, smoking among kids is still at historically high levels.
      Over the past 10 years the number of kids under 18 who become daily smokers each
      year has increased by more than 70 percent.

PMID- 11987648
TI  - Recognizing nursing's independent license: prescriptive authority for APNs.
AB  - A landmark study, published in the Yale Journal on Regulation by Yale Law School
      Dean Barbara J. Safriet, addresses the cost effectiveness and quality of advanced
      practice nurses: "Since the productivity of [APNs] has been demonstrated by the
      fact that they can provide equal care for a full range of health services
      traditionally provided by physicians, and since their training costs and
      employment costs are substantially less than those of physicians, it appears
      indisputable that they are truly cost-effective health care providers. This cost
      effectiveness, combined with their proven ability to provide quality care to a
      large number of people, suggests that they should play a central role in the
      solutions currently being developed for our health care crisis. Despite their
      proven and potential contributions, however, several unnecessary barriers stand
      in the way of their full utilization.... Chief among these are conflicting and
      restrictive state provisions governing the scope of practice and prescriptive
      authority of [APNs].... As a result of these provisions, [APNs] are severely
      hampered--or disabled altogether--in their efforts to fulfill their fully proven
      potential to enhance our nation's health.... Prescriptive authority is central to
      APNs' effective practice.... States that limit APNs to a physician-dependent
      scope of practice, including prescriptive authority, actively impede the public's
      access to safe and effective health care."

PMID- 11987649
TI  - Environmental quality as a public health issue.
AB  - Mercury is a persistent, bio-accumulative toxin that has been linked to numerous
      health effects in wildlife and humans. Mercury is a potent neurotoxin which may
      also harm the brain, kidneys and lungs. The unborn child and young infants are at
      special risk of brain damage from mercury exposure. Hospitals' use of mercury in
      chemical solutions, thermometers, blood pressure gauges, batteries, and
      fluorescent lamps make them large contributors to the overall mercury emission
      into the environment. Most hospitals recognize the dangers of mercury. In a
      recent survey, 4 out of 5 hospitals asked have policies in place to eliminate the
      use of mercury containing products and 62% require vendors to disclose the
      presence of mercury in chemicals that the hospital purchases. Only 12% distribute
      mercury-containing thermometers to new parent. Ninety two percent teach their
      employees about the health and environmental effects of mercury and 46 percent
      teach all employees how to clean up mercury spills. However, the same study
      showed that many hospitals have not implemented those policies. Forty two percent
      were not aware if they still purchased items containing mercury. In addition, 49%
      still purchase mercury thermometers, 44% purchase mercury gastrointestinal
      diagnostic equipment, and 64% still purchase mercury lab thermometers.

PMID- 11987650
TI  - Why you should be active in our political process.

PMID- 11987651
TI  - PACs ensure nursing's seat at the policy-making table.

PMID- 11987652
TI  - The role of memory strategies in medication adherence among the elderly.
AB  - Research shows that older adults use memory strategies as a compensatory
      mechanism for coping with age-related memory loss. This research investigated the
      type of memory strategies used by older adults living independently in the
      community in adhering to their prescription medications. Older adults reported
      greater use of internal memory strategies and a preference for event-based over
      time-based prescription medication instructions. Depression and memory anxiety
      were significant predictors of type of medication adherence strategies used among
      the elderly. Health status and social support were not major determinants of the
      type of medication adherence strategy used.

PMID- 11987653
TI  - The new senior volunteer: a bold initiative to expand the supply of independent
      living services to older adults.
AB  - This article presents findings of the evaluation of the Experience Corps for
      Independent Living (ECIL) initiative. The ECIL initiative was a two-year
      demonstration program designed to test innovative ways to use the experience,
      time, and resources of volunteers over 55 to significantly expand the size and
      scope of volunteer efforts on behalf of independent living services for frail
      elders and their caregivers in specific communities. Six demonstration sites were
      selected to participate in this initiative. The intensive volunteers, the
      critical component of the program, were more highly skilled than typical
      volunteers from existing senior volunteer programs. ECIL volunteers collaborated
      with agency partners to develop new programs, supervise direct service
      activities, and enhance the performance of the agencies being served. The ECIL
      initiative was particularly successful in meeting its goals of expanding the
      supply of independent living services to frail elders and their families in the
      communities served.

PMID- 11987654
TI  - The comparative performance of for-profit and nonprofit home health care services
      in the US.
AB  - OBJECTIVE: To determine, by way of an exhaustive, systematic, and comprehensive
      review and summary of all scientific published studies, whether or not there are
      any performance differences between private for-profit and private nonprofit home
      health care providers. The second objective is to discover the proportion of all
      research on this topic that is devoted to home health care services compared to
      all other health services providers. DATA SOURCES: Computerized bibliographic
      searches of relevant databases and published indexes and abstracts were
      undertaken. They included Medline (Ovid and Pubmed versions), Web of Science
      (Social Sciences Citation Index and Science Citation Index), ABI/Inform, and
      Sociological Abstracts. Follow-up searches of reference lists in each article
      obtained from the computerized search were then completed. STUDY DESIGN: This
      systematic review retained for analysis all published studies that compared the
      performance of for-profit and nonprofit health care providers on access, quality,
      cost/efficiency, and/or amount of charity care, based on data collected after
      1980. As a quality control measure only studies published in peer reviewed
      journals were included. Studies were coded according to the article's stated
      conclusions: for-profit superiority, nonprofit superiority, or no
      difference/mixed results. PRINCIPAL FINDINGS: The comparative performance of for
      profit and nonprofit home health service organizations is one of the most
      understudied areas of health care provider services in the US today. Only 6 of
      the over 1030 comparisons of the two concerned home health care. No data on this
      topic have been collected since 1991, and no articles about it have been
      published in a peer-reviewed journal since 1995. CONCLUSION: Research on the
      relative performance of for-profit and nonprofit home health care services is a
      research priority urgently in need of attention.

PMID- 11987655
TI  - Access of target groups to 1915(c) Medicaid home and community based waiver
      services.
AB  - OBJECTIVES: The study examined the access of specific target groups to the
      1915(c) home and community based waiver program in terms of the number of
      participants, services, and expenditures for 1992 and 1997. METHODS: The study
      collected HCFA 372 waiver program statistics from each of the states and compared
      statistics for the two time periods. A regression examined the increase in
      program expenditures. RESULTS: An unequal distribution of HCBS expenditures
      across target groups was found where individuals with developmental disability
      were 39 percent of participants but used 77 percent of the total $7.9 billion
      waiver expenditures in 1997. The aged and disabled were 58 percent of waiver
      participants but received 21 percent of expenditures. The program growth was
      primarily due to increases in participants and reimbursement rates. CONCLUSIONS:
      Individuals with MR/DD used more costly services such as habilitation and
      residential care than other target groups. Studies are needed to examine what
      accounts for the unequal access and whether program expenditures are sufficient
      to meet the long-term care needs of various target groups.

PMID- 11987657
TI  - Caries prevalence, oral hygiene and orthodontic status of Saudi Bedouin children.
AB  - The objectives of the study were to determine caries prevalence, oral hygiene and
      orthodontic status of Bedouin children in a desert around Al-Qasseem Region of
      Saudi Arabia. One hundred and fifty three children were examined for caries, oral
      hygiene and orthodontic status with mirror and explorer utilizing natural light.
      These children were divided into two groups for analyses. The primary dentition
      group consisted of 77 children, 39 (50.6%) male and 38 (49.4%) female with a mean
      age of 4.0 (+/- 1.4) years. The mixed dentition group consisted of 76 children,
      67 (88.2%) male and 9 (11.8%) female with a mean age of 9.7 (+/- 2.9) years. In
      Primary dentition group, 16 (20.8%) children were caries positive and mean DMFT
      was 0.91 (+/- 2.42). There was a highly significant relation (p < .001) between
      oral hygiene and caries. In the mixed dentition group, 15 (19.7%) children were
      caries positive. The mean DMFT and DMFT scores for these children were 0.72 (+/-
      1.96) and 0.74 (+/- 1.48) respectively. There was a significant relation (P >
      .01) between oral hygiene and caries. One hundred and fifty one (98.6%) children
      had class I molar relation and 2 (1.4%) children had class II molar relation.
      Anterior open bite, anterior crossbite and posterior crossbite were found in one
      case (0.7%) each. The caries experience of these Bedouin children was low both in
      terms of prevalence and severity. There was a significant relation between oral
      hygiene and caries. The orthodontic problems were almost nonexistent in the study
      population.

PMID- 11987658
TI  - Evaluation of panoramic radiography and axial computed tomography in cases of
      ameloblastoma and central giant cell granuloma of mandible.
AB  - Evaluation of mandibular mass lesions is a perplexing clinical problem. Some of
      these lesions have very similar clinical presentation and even similar or
      overlapping imaging features. Plain radiographs and orthopantomograms are
      frequently requisitioned for the diagnosis and are helpful in localization and
      characterization of these lesions. However, the specificity of diagnosis remains
      low. A study was undertaken to further characterize these lesions using Computed
      Tomography (CT) and analysis of cross sectional images of various mandibular mass
      lesions. Of these, imaging features of ameloblastoma and central giant cell
      granuloma (CGCG) were studied and compared, which is reported in this paper.

PMID- 11987659
TI  - Ultrasonographic evaluation of salivary gland diseases.
AB  - Ultrasonography is an imaging modality in which the high frequency sound waves
      are sent into the tissues and the acoustic impedence of the tissues are received,
      amplified and imaged. The echoes of the tissues vary according to their
      densities. Ultrasonography is applied in the field of medicine, in the evaluation
      of soft tissues, to record their movements and to assess their vascularity. In
      the oro-facial region, ultrasonography is employed in the evaluation of salivary
      glands, cervical lymph nodes, in soft tissues and post-operative swellings. Ten
      interesting cases of salivary gland diseases are presented here, each case
      showing a characteristic sonographic feature and providing a useful diagnostic
      clue in the identification of the disease.

PMID- 11987660
TI  - Orthodontic tooth movement and bioelectricity.
AB  - Research in the field of orthodontics is now focused on the biology of tooth
      movement. Advanced molecular biology techniques has showed the researchers new
      avenue towards finding answers to the questions asked for the last few decades.
      Now it is possible for the researches to explore the lacunae in the field. One
      such field is, pharmaco-therapeutically or electrophysiologically enhancing the
      rate of tooth movement, improving the stability of the results, augmenting the
      anchorage. The voltage gated channels of cell membrane of connective tissue cells
      of the periodontal ligament can be modulated by electrophysiological ways. The
      application of an electric current may alter the electrolytic environment
      allowing changes in the type and rate of ions that move across the cell
      membranes. Changes of the flux of K+, Ca++, Na+, Mg+, and Cl. can act as a
      mediator for cellular changes. Micro-pulsed electrical stimulation could reach
      bone osteoblasts non-invasively and this current can result in an increase in the
      cAMP and cGMP. These cyclic nucleotides are a type of second messenger, which
      play a role in the efficient remodeling of alveolar bone and in including more
      tooth movement. This article discusses the role of electrical potential in
      orthodontic tooth movement, methodology of studying the electrophysiology of cell
      membrane and the recent advances in the field and its possible clinical
      application.

PMID- 11987661
TI  - Evaluation of the polished surface characteristic of cobalt-chrome castings
      subsequent to various finishing and polishing techniques.
AB  - Finishing and Polishing constitutes an essential requisite after the fabrication
      of removable partial dentures. Improper finishing and polishing of cast framework
      will adversely affect the quality of functional units of partial dentures due to
      reduced dimensions. In this study the polished surface characteristic and loss of
      weight of the casting were evaluated and compared following different finishing
      and polishing techniques. A total number of thirty test specimens were cast and
      each surface finishing and polishing technique was carried out with a high speed
      polishing motor and an electropolishing unit under standardised conditions.
      Surface roughness was evaluated by means of a surface roughness analyzing
      instrument, Perthometer. The loss of weight due to the metal lost was observed on
      a sensitive electronic balance. The results of polishing technique employed with
      G3 group revealed better surface characteristic. It may be understood that
      sandblasting causes initial roughness and the sequence of coarse cylindrical
      abrasive, Black hard rubber polisher (coarse grit-Dentauram), Grey hard rubber
      polisher (Med-grit-Dentauram), Green hard rubber polisher (Fine-grit-Dentauram),
      Grey flexible rubber polisher (Fine grit-Renfert), felt buff with pumice slurry
      and felt buff with green polishing compound (Degussa) produced improved surface
      in this case. The loss of weight due to metal lost show concern with technique
      groups G4, G5, G6. It can be avoided by judicious sandblasting and application of
      proper grit of abrasive agents.

PMID- 11987662
TI  - Determinants of dental caries experience.

PMID- 11987663
TI  - Lip prints (cheiloscopy).
AB  - External surface of the lip has many elevations and depressions forming a
      characteristic pattern called lip prints, examination of which is referred to as
      cheiloscopy. This is unique for individuals like the finger prints. The
      biological phenomenon of systems of furrows on the red part of the human lips was
      first noted and described by anthropologist R.S. Fischer, in 1902. However until
      1930, anthropology merely mentioned the existence of furrows without suggesting a
      practical use for the phenomenon. Since 1950, the Japanese have carried out
      extensive research in this matter. In the period 1968 to 1971, Y.T Suchhihashi
      and T. Suzuki examined 1364 persons at the department of forensic odontology at
      Tokyo university and established that the arrangement of lines on the red part of
      the human lips is individual and unique for each human being. Lip print recording
      is helpful in forensic investigation that deals with identification of humans,
      based on lip traces. A lip print may be revealed as a surface with visible
      elements of lines representing the furrows. This characteristic pattern helps to
      identify the individuals since it is unique for individuals. When the lines are
      not clear (Only the shape of lines is printed), individual identification of
      human being based on this trace is extremely difficult, unless the trace contains
      more individual characteristics like scars, clefts etc, and often identification
      ends with group identification.

PMID- 11987664
TI  - Ameloblastic carcinoma. A case report with review of literature.
AB  - Ameloblastic carcinoma is a rare odontogenic malignant tumour and has been a
      subject of great debate in literature. It does challenge the diagnostic acumen of
      pathologists, as this lesion needs to be detected at an early stage for adequate
      therapy. We present a case of the same with literature review.

PMID- 11987665
TI  - Regional odontodysplasia (Ghost teeth). A case report.
AB  - Regional odontodysplasia is a rare development anomaly affecting the teeth with
      an unknown etiology. This dental abnormality involves the hard tissues of the
      teeth that are derived from both epithelial (enamel) and mesenchymal (dentine &
      cementum) components of the tooth forming apparatus. Teeth in a region or
      quadrant of maxilla or mandible are affected to the extent that they exhibit
      short roots, wide open apical foramen and large pulp chamber, the thinness and
      poor mineralisation qualities of th enamel and dentine layers have given rise to
      a faint radiolucent image, hence the term "Ghost teeth". Both the permanent teeth
      and the deciduous teeth are affected. Females are more commonly affected than
      males. There is a maxillary predominance (2.5:1) with a predilection for the
      anterior teeth. Eruption of the affected teeth is delayed or does not occur.
      Because of the poor quality of the affected teeth, they cannot be rehabilitated
      for functional use therefore the treatment of choice is extraction with
      prosthetic replacement. However, necrosis and facial cellulitis appear to be a
      complication if these teeth are retained. A unique case of regional
      odontodysplasia affecting the entire right quadrant of mandible is reported here.

PMID- 11987666
TI  - Gorlin syndrome. A case report.
AB  - Gorlin's syndrome is a genetic disorder of autosomal dominant inheritance with
      high penetrance and variable expression. It embraces a constellation of many
      organs principally affects the skin, skeleton, and endocrine and nervous system.
      A rare case is reported to illustrate the features of Gorlin's syndrome without
      the features of basal cell carcinoma and to emphasize the need for early
      recognition and careful follow up by the dentist prevent severe sequelae.

PMID- 11987667
TI  - [Renal markers and predictors, and renal and cardiovascular risk factors].
AB  - An important task of the nephrologists during the last century, it has been the
      search of elements and means that allow us, with the adequate precision, to
      correlate the functional deterioration of the kidney, and the patient's clinical
      reality. And the continuous searching of factors and markers that injure them,
      the prognosis, and early diagnosis, to be able to predict the degree of the
      organs and patient's survival. Almost parallel survival presage in the natural
      history of the illness, almost one century ago. In the second half of the XX
      century, in the developed countries, appear modifications of the social,
      cultural, and sanitary conditions, that make appear some very different partner
      sanitary and epidemic circumstances, and take place like they are, among others:
      1. An increase of per capita private rents, what takes place to increase of the
      level of social life and the population's health. With increment of the
      longevity, and smaller incidence and prevalence of classic process, as
      malnutrition, infections, infantile mortality, so increasing the weight of the
      cardiovascular diseases and death. This is potentiated for the increment and the
      incidence of environmental cardiovascular risk's factors (like high caloric and
      fatty-rich diets, smoke, alcohol, disappearance of the physical work, inactivity,
      etc). And that situations are also product of the change of the outline of human
      and social values and guides. 2. Access of the whole population to a sanitary
      attention of more quality and effectiveness. It allows the biggest survival of
      patients that suffer vascular crisis, (as angina, miocardial infarction or
      cerebrovascular accident), that few years ago they have had a higher
      morbimortality and an inferior survival (2). 3. The execution of big epidemic
      studies has been able to, not only characterize and test with scientific evidence
      to numerous factors and markers, that induce renal and cardiovascular prejudicial
      changes, but risk and death probability prediction. And also, its possible
      association nexuses, its injuring mechanisms, and the characterization of the new
      "emergent" renal and cardiovascular risk's markers and factors. 4. The impact on
      the possibility to treat the end stage renal disease with effective and prolonged
      procedures, by hemodialisis or kidney transplantation, has been occurred. The
      affected population's survival with the adequacy renal-sustitution treatment, and
      the possibility of indefinite duration of its treatment, has also impacted on the
      public health, and its resources, in an evident way. Simultaneously to increase
      of the incidence in the population, the electivity for the treatment has been
      enlarged and extended increasing it exponentially. These facts are documented
      here, and are defined the characteristics of the factors and markers of risk, of
      renal and cardiovascular diseases. The defined factors are valued to mark, so far
      as with the well-known evidence is possible, the prediction and the progression
      of the renal and cardiovascular functional deterioration: The hypertension,
      cardiovascular remodeling, the arterial stiffness, the heart rate, the
      sympathetic activation, the modification of the physiological response of the
      target organ to the overcharge, the metabolic syndrome, the obesity, the insulin
      resistance, the altered lipid profile, and metabolism of the fatty acids, the
      salt-sensibility, the decrease of the renal functional reserve, the glomerular
      hyperfiltration, the absence of the arterial pressure nocturnal descent, the
      abnormal excretion of proteins for the urine, the phenomenon induced by
      dysfunctions of the clotting, superoxide production, growth factors, the
      production of chronic inflammation and its markers, the factors of the
      glomerulosclerosis progression, the hyperuricemic status, the endothelial
      dysfunction and others, are evaluated. As well as their association among them
      and with other factors of risk not changeable like the age, and in turn, with
      other acquired voluntarily factors of risk, as the smoking habit and the alcohol.
      These facts are now impacting on the population's sanity. And also in the
      professional nephrologic exercise, so much for the cardiovascular and renal
      morbimortality increased, as for the increase of the incidence of end-stage renal
      disease susceptible to treat with of substitutive procedures. They try to justify
      the sentence of Alan Weder of the heading, and other concepts like "epidemic
      factors of the XXI century", and intuitive expressions like "predialitic
      endothelial disruption or ruin".

PMID- 11987668
TI  - [Renal and cardiovascular protection associated to antihypertensive treatment in
      the elderly].
AB  - The incidence of arterial hypertension increases with age in such a way that by
      the age of 60 the incidence is greater than 50% in men and women. This increase
      is particularly relevant if we consider the changes in systolic blood pressure
      (increase) and diastolic blood pressure (decrease) in relation to age and as a
      consequence in the reduction of vascular compliance which is common in men and
      women over the age of 60. These disorders are associated to artheriosclerosis and
      the corresponding increase in pulse pressure. It is for these reasons that the
      most common form of hypertension is isolated systolic hypertension (SBP > 140
      mmHg and SBP < 90 mmHg), which represents 50% of hypertensive patients in the
      elderly population. Isolated systolic hypertension is also associated to an
      increase in cardiovascular disease (MI, stroke), increasing the risk of mortality
      four times. In elderly people, hypertension and isolated systolic hypertension
      are risk factors that can be managed. Today there is sufficient evidence from
      clinical trials that show a clear benefit in the reduction of the cardiovascular
      and renal risk associated to the antihypertensive treatment in the elderly, at
      least when the blood pressure is greater than 160/90 mmHg. The target blood
      pressure figures to control in the elderly person, probably below 160/90 mmHg,
      still need to be determined.

PMID- 11987669
TI  - [Arterial hypertension and renal vascular disease: nephroangiosclerosis].
AB  - Nephroangiosclerosis and nephrosclerosis are terms used to define the renal
      disease induced by essential hypertension. The predominant histologic changes
      occur in the preglomerular microvasculature. Epidemiological data about the risk
      of hypertensive patients from developing renal failure offer conflicting results.
      Nevertheless, renal vascular disease, including nephroangiosclerosis and/or
      ischemic nephropathy, appears to be an important cause of end-stage renal
      disease. Presumably, nephrosclerosis is the renal expression of systemic
      atherosclerosis: male sex, age > 55-60 years, black race, high serum cholesterol
      and/or uric acid levels, and coronary heart disease, peripheral artery disease,
      and/or cerebrovascular disease are common associations with the renal alteration.
      Treatment strategy should include an intensive blood pressure control, probably
      below 130/80 mmHg, together with antiplatelet and lipid-lowering agents when
      necessary. Although specific studies are lacking, ACE inhibitors and angiotensin
      II antagonists may offer additional benefits in slowing the renal disease
      progression.

PMID- 11987670
TI  - [Diabetic nephropathy: strategies for prevention].
AB  - A cumulative incidence of diabetic nephropathy of 30-35% has been documented
      after duration of diabetes of at lest 25 years in type 1 diabetes mellitus and 15
      25% in type 2 diabetes mellitus. Diabetic Nephropathy has become the leading
      cause of chronic renal failure. Several strategies has been suggested to prevent
      renal disease in patients with diabetes mellitus. Two main treatment strategies
      for primary prevention of diabetic nephropathy are improved glycaemic control and
      lowering the blood pressure particularly with angiotensing-converting-enzyme
      inhibitors. Other therapeutics include, lipid-lowering therapy, dietary protein
      restriction, smoking cessation and aspirin therapy.

PMID- 11987671
TI  - [Dyslipidemia and cardiovascular risk in type 2 diabetes mellitus patients with
      associated diabetic nephropathy].
AB  - BACKGROUND: Diabetes patients with concomitant diabetic nephropathy are
      especially destined to cardiovascular complications due to the presence of
      microalbuminuria or proteinuria, that are potent inductors of dyslipidaemia.
      METHODS: We have studied 98 type 2 diabetes mellitus patients, 61 male and 37
      female, mean age 63 +/- 13 year old, all of them with overt proteinuria (above
      500 mg/day), divided into 4 groups: G-I (n = 13): patients with t. cholesterol >
      6.25 mmol/l treated with fibric-acid derivatives; G-II (n = 52):
      hypercholesterolemic patients treated with statins; G-III (n = 20):
      hypercholesterolemic patients with no lipid-lowering intervention; G-IV (n = 13):
      normocholesterolemic patients (control group). Lipidic profile, proteinuria and
      renal function have being compared after 1, 3 and 5 years. RESULTS: Base-line
      characteristics of the patients were similar when regarding age, onset of
      diabetes or nephropathy. Only proteinuria was higher in statins-treated group (p
      < 0.05). Fibric-acid derivatives were more effective on hypertriglyceridaemia
      while statins were more effective lowering LDL cholesterol. A gemfibrocyl-treated
      patient presented a rhabdomyolysis episode. Statins were safe and well tolerated.
      Nine patients (19%) in G-II, 2 patients (10%) in G-III and 1 patient (7%) in G-IV
      achieved end-stage renal failure. Five-year cardiovascular mortality and all
      cause mortality rate were 23%/23% in G-I, 13%/19% in G-II, 20%/25% in G-III and
      31%/31% in G-IV. The difference was statistically significant when comparing
      normocolesterolemic versus statin-treated patients (p < 0.05). CONCLUSION: Lipid
      lowering therapy could probably delay but not avoid the progression of diabetic
      nephropathy. Since dyslipidaemia is closely related to the progression of
      cardiovascular disease and mortality, an aggressive lipid-lowering therapy is
      recommended, irrespectively of its potential effect on diabetic nephropathy.

PMID- 11987672
TI  - [Cardiovascular risk factors in chronic renal failure].
AB  - Cardiovascular complications are the main cause of death in patients with chronic
      renal disease. These complications are due to two important morphological
      changes. Firstly, left ventricular hypertrophy together with the changes in the
      cardiac remodelling and myocardiac fibrosis constitute the lesion with the
      highest incidence in renal chronic disease. Secondly, disease in the large
      arteries (macrovascular disease) involve two types lesions: Artherosclerosis,
      which is characterised by the formation of plaques in the intima arterial
      membrane and artherosclerosis due to lesions in the media arterial membrane,
      which causes a loss in elasticity of the arterial tree.

PMID- 11987673
TI  - [Cardiovascular risk in patients with chronic renal failure. Patients in renal
      replacement therapy].
AB  - Dialysis patients constitute a high-risk subset of patients for developing
      cardiovascular disease, which accounts for nearly 50% of deaths. After
      stratification for age, race and gender, cardiovascular mortality is 10-20 times
      higher in dialysis patients than in the general population. Cardiovascular
      disease in this population cannot be fully explained by the high prevalence of
      classical cardiovascular risk factors (age, hypertension, diabetes,
      hyperlipidemia, smoking, etc.). Thus, the involvement of "new" cardiovascular
      risk factors (hyperhomocysteinemia, hyperfibrinogenemia, high lipoprotein (a)
      levels, oxidative stress, inflammation, etc.), and uremia-related factors
      (anemia, impaired calcium-phosphorus metabolism, hyperparathyroidism,
      accumulation of endogenous inhibitors of nitric oxide synthesis, etc.) has been
      also invoked to play a role in the increased cardiovascular risk in these
      patients. Endothelial dysfunction is the initial event in the development of
      atherosclerosis. Uremic patients exhibit an endothelial dysfunction, even before
      starting dialysis, which persists o is even aggravated under dialysis treatment.
      Uremic patients must be considered at high risk of developing cardiovascular
      disease. Thus cardiovascular risk factors in these patients should be managed
      early, aggressive and multifactorially in order to reduce their high
      cardiovascular morbidity and mortality.

PMID- 11987674
TI  - [Cardiovascular risk in the kidney transplant patient].
AB  - Renal transplants have experienced a spectacular development in recent years,
      significantly improving the quality of life and life expectancy of patients.
      However, mortality due to cardiovascular disease in recent years has become the
      first cause of death in renal transplant patients, ahead of infections and
      neoplasic disorders. The causes of this increase are due to the following
      reasons: 1) Important changes in the characteristics of the donor and the renal
      receptor. 2) A significant decrease in the immediate post-transplant mortality
      rates, and 3) increase in the incidence of cardiovascular risk factors in
      transplant patients.

PMID- 11987675
TI  - [Genes and kidney disease. Candidate genes].
AB  - Molecular biology techniques have provided important advances in the search for
      causal relationships in complex diseases supporting traditional epidemiologic
      studies. Genetic epidemiology allows us to detect genetic variants that could be
      related to the onset and progression of different diseases. In cardiovascular and
      renal diseases, this approach linking traditional risk factors to new described
      ones and those allelic variants, which contribute to the development of these
      manifestations permits a better understanding of individual disease
      susceptibility. This is usually afforded through case-control studies evaluating
      allelic variants of candidate genes previously associated with the disease. Even
      in this candidate gene search, association-based methods are more powerful than
      linkage studies in complex traits if we assume that some of the typed
      polymorphisms are causative although with subtle phenotypic effects. Some brief
      examples may illustrate the progress in the understanding of renal and
      cardiovascular diseases.

PMID- 11987676
TI  - [Polymorphism of the renin-angiotensin system and renal failure].
AB  - The renin-angiotenin-aldosterone system (RAAS) is not only involved in
      cardiovascular disease but also in renal pathophysiology and progression of renal
      disease. Several polymorphisms of genes coding for components of the RAAS have
      been identified. The I/D polymorphism of the ACE gene, a variant of the
      angiotensiogen gen, the M235T polymorphism, and the variant A1166 C polymorphism
      of the angiotensin II type 1 receptor gene are the most important. Several
      studies have suggested a potential role for I/D polymorphism of the ACE gen in
      the progression of renal diseases and in the cardiovascular death rate of
      patients with renal failure. Data on RAAS polymorphisms as determinants of the
      prevalence of renal diseases and the response to renoprotective therapies are
      conflicting. Given the polygenic nature of renal and cardiovascular disease and
      the growing number of candidate genes, large prospective and collaborative
      studies are required to assess the effect of RAAS polymorphisms on the
      progression of renal disease and on the response to renoprotective therapies.

PMID- 11987677
TI  - [Biopsy of sub-optimal renal donors. Significance of the correct evaluation].

PMID- 11987678
TI  - [Should we try to dialyze elderly patients or not?].

PMID- 11987679
TI  - [Should separate hemodialysis rooms be used for patients with HCV? A personal
      opinion].

PMID- 11987680
TI  - [Physical activity as modifier of renal function. Historical review].

PMID- 11987681
TI  - [Mycophenolate mofetil in lupus nephritis].
AB  - The treatment of severe lupus nephritis is based on the combination of steroids
      and cytotoxic drugs. Intravenous cyclophosphamide administered in "pulses" is
      effective in the induction of remission but other therapeutic alternatives are
      sought in refractory cases or severely relapsing patients. Mycophenolate mofetil,
      used in renal transplantation, also can be useful in severe lupus nephritis. We
      describe the evolution of 6 patients (5 women and 1 man; age 17-45 years) with
      severe lupus nephropathy who after achieving remission with intravenous
      cyclophosphamide and steroids (5 cases) or cyclosporin A (1 case) showed relapse
      of proteinuria and were treated with mycophenolate mofetil (dose 1000-2000
      mg/day). Two patients have completed 24 months, 1 patient two cycles of 12
      months, 2 patients 18 months and 1 patient 6 months. After this treatment, all
      patients have achieved remission (3 partial and 3 complete). There was no
      treatment failure and no one patient discontinued medication; however 1 case
      relapsed. There were no changes in leucocytes, haemoglobin, serum creatinine and
      serum albumin. ANA and alpha DNA antibodies decreased. Proteinuria (measured as
      protein/creatinine urine ratio: initial 3 and final 0.3) and dose of steroids
      (initial: 17.5 mg/d and final 5 mg/d) decreased significantly (p < 0.05 Wilcoxon
      t-test). The most common side effects were nausea and abdominal discomfort that
      improved without discontinuation of treatment. We conclude that mycophenolate
      mofetil is effective and a safe drug in severe relapsing lupus nephritis.

PMID- 11987682
TI  - [Uremic media affects hemostatic properties of human endothelial cells in culture
      and increases the production of von Willebrand factor].
AB  - We have investigated the ability of serum from uremic patients to modify the
      thrombogenic properties of the endothelium. The effect of the uremic media on the
      morphology of ECs, and their resistance to flow was analyzed. The reactivity of
      the extracellular matrix (ECM) generated by ECs towards normal platelets was
      evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic media
      resulted in abnormal morphology and signs of accelerated growth. Detachment of
      ECs exposed to circulating blood was increased when cells had been grown with
      media supplemented with uremic serum (22% vs 13%). Platelet deposition and
      formation of aggregates were significantly elevated on ECMs generated in the
      presence of uremic media (40.23 +/- 6.43% vs 25.42 +/- 2.69%, p < 0.05, n = 5).
      Immunocytochemical methods detected an enhanced expression of von Willebrand
      factor antigen on uremic ECMs (uremic 17.1 +/- 4.2% vs control 13.57 +/- 3.98%, p
      < 0.05) and its mRNA expression in endothelial cells (uremic 213.24 +/- 6.13 vs
      control 200.77 +/- 7.52, p < 0.05). These results suggest that uremic medium
      alters endothelial function and impairs the antithrombotic functions of cultured
      endothelial cells. This effect may contribute to the increased cardiovascular and
      thrombotic risk reported in ESRD patients.

PMID- 11987683
TI  - [New knowledge on HLA class II molecules and a better selection of organs for
      transplantation].

PMID- 11987684
TI  - [Peritoneal anionic transfers and their relationship with peritoneal transport
      and acid-base status].
AB  - This study was designed to assess lactate and TCO2 transfers during PET and in 24
      hour drained dialysate, relating them with the membrane transport type and acid
      base status. Forty PETs were studied, performed in 23 clinically stable patients
      maintained on CAPD for 6.5 +/- 3 months using 35 mEq/l of lactated-based
      dialysate. No significant changes in plasma concentration of lactate and TCO2
      were observed. Lactate gain (LG) was 51.91 +/- 4.86 and 220.82 +/- 22.61 mEq and
      TCO2 loss was 46.49 +/- 6.9 and 183.51 +/- 32.9 mEq during PET and 24 h
      respectively. When analyzed these transfers according to membrane transport
      characteristics (High/High-average group: HHAG and low/low-average group: LLAG),
      LG was significantly higher (53.94 +/- 3.7 vs 48.86 +/- 4.8 mEq during TEP p <
      0.01, and 228.06 +/- 15.6 vs 209.96 +/- 27.2 mEq during 24 h p < 0.05). TCO2 loss
      was greater (48.66 +/- 7.15 vs 43.25 +/- 5.5 mEq p < 0.05 and 187.22 +/- 27.3 vs
      177.93 +/- 35.3 during PET and 24 h respectively) in HHAG vs LLAG. When
      evaluating transfers according to patients' acid-base status (normal and acidotic
      group), no significant differences were found in LG, but there was a significant
      difference in TCO2 loss (47.7 +/- 5.9 vs 39.76 +/- 6.1 mEq p < 0.01). We did not
      observe significant differences in acid-base balance during PET according to
      membrane transport characteristics (HHAG vs LLAG). However, acid-base balance was
      more positive in acidotic patients' PET than in normal patients (9.87 +/- 6.6 vs
      3.92 +/- 6.8 mEq p < 0.05). TCO2 loss during PET directly correlated with plasma
      TCO2 concentration pre-PET (r: 0.43, p < 0.01). However no significant
      correlation was found between plasma lactate levels and lactate gain during PET.
      In conclusion, the lactate gain and bicarbonate loss account for the net dialytic
      base balance during PET and 24 h. However, the peritoneal membrane transport
      characteristics as well as the acid-base status can determine a higher or lower
      aionic transfer (lactate and bicarbonate).

PMID- 11987685
TI  - [Prognostic significance of programmed dialysis in patients who initiate renal
      substitutive treatment. Multicenter study in Spain].
AB  - BACKGROUND: The aim of our study was to analyse patient characteristics,
      mortality and costs, all of them in relation to whether starting dialysis was
      planned or unplanned. METHODS: A total of 362 patients (227 male and 135 female)
      from five hospitals of the National Health System, who were started on chronic
      renal replacement therapy (RRT) during 1996 and 1997 were included. Patients who
      were started on RRT after acute renal failure were excluded. We carried out a
      retrospective analysis of the demographic characteristics, patients' conditions
      at the time of initiating dialysis and outcome and costs at six and thirty-six
      months of treatment. Patients were classified as planned (PL-D) or unplanned
      dialysis (UNPL-D), depending on whether or not the patient had a vascular or
      peritoneal access ready to use for initiating RRT. RESULTS: One hundred and
      eighty-six patients (51.4%) started on dialysis in the PL-D group whereas 176
      (48.6%) did it as UNPL-D. In this latter group, 135 (37.3% of the total) had
      previously been monitored by a nephrologist, and 41 (11.3%) initiated dialysis
      without previous nephrological follow-up. UNPL-D was associated with older age (p
      < 0.001), non-nephrological follow-up (p < 0.001), diabetes (34.7% vs 22.6%) (p =
      0.011), haemodialysis as a first mode of RRT (94.9 vs 81.7%) (p < 0.001), higher
      comorbidity risk (p < 0.001), dialysis initiation with uraemic symptoms or fluid
      overload (p < 0.001), increased blood transfusion requirement (p < 0.001) and
      lower serum albumin (p < 0.001), creatinine clearance (p < 0.001), haemoglobin
      concentration (p < 0.001), and weight (p = 0.002). In the PL-D group the main
      primary renal diseases were glomerular and polycystic disease, whereas
      interstitial and diabetic nephropathy were higher in UNPL-D group (p = 0.005).
      Multivariate analysis showed that previous non nephrological follow-up, uraemic
      symptoms, interstitial nephritis as primary renal disease correlated with UNPL-D
      initiation, and it was followed by choosing haemodialysis as first RRT. UNPL-D
      was also associated with increased number of days of hospitalization at the
      initiation of dialysis, and during the first 6 months (p < 0.001), increase of
      hospitalization days (p = 0.009), and increased 6-month-mortality (10.2% vs 3.2%)
      (p = 0.015, log rank test), and three-year mortality (24.2 vs 36.9%) (p = 0.006,
      log rank test). The costs of UNPL-D were fivefold that of the PL-D group.
      CONCLUSION: UNPL-D has been associated with worse overall clinical conditions at
      the initiation of chronic replacement therapy, choosing haemodialysis as first
      RRT, increased morbi-mortality and subsequent increase of costs.

PMID- 11987686
TI  - [Ischemic cadiopathy in patients undergoing chronic hemodialysis].
AB  - We report a retrospective study of patients on chronic hemodialysis in whom a
      diagnosis of ischemic heart disease had been established. We compared the
      findings on coronary cineangiography and the treatment (medical only, surgical
      revascularisation [CABG] and percutaneous transluminal coronary angioplasty
      [PTCA]) with the early and late evolution. From a population of 2,287 patients on
      chronic hemodialysis treatment during the 5 year period 1994-1999, 83 patients
      who underwent coronary cineangiography after starting dialysis were selected.
      Their mean age was 63 +/- 9.4 (39-80) and the mean time on hemodialysis was 6
      years (6 months-19 years). RESULTS: 65 patients (78%) had severe coronary
      lesions, 40% of whom had three vessel disease. 14 patients had medical treatment
      only (group 1), 23 had CABG (group 2) and 28 PTCA (group 3). Mortality within 30
      days of intervention was 13% in group 2 and 21.4% in group 3. Global survival at
      two years was 82% in group 2 and 69% in group 3. Survival without angina at 6 and
      24 months were 69% and 46% in group 2 and 55% and 22% in group 3 respectively.
      Survival without acute myocardial infarction at 6 and 24 months was 95% and 95%
      in group 2 and 89% and 64% in group 3. Data analysis using Cox proportional risk
      model showed that PTCA posed a higher risk of angina and death than CABG.
      CONCLUSION: Surgery yielded better early and later results than angioplasty even
      in those patients with severe coronary artery disease.

PMID- 11987687
TI  - [Anti-CD25 monoclonal antibody against polyclonal antibodies in pediatric renal
      transplantation].
AB  - Although usually reversible, acute rejection of kidney graft is a negative factor
      in long-term graft survival. Commonly used in pediatric renal transplantation,
      immunosuppresive induction therapy is established to prevent it. New
      immunosuppressive agents have been developed in recent years and among them anti
      CD25 monoclonal antibody appears to be specially interesting. AIM: To evaluate
      efficacy and safety of anti-CD325 monoclonal antibody (basiliximab) versus
      polyclonal antibodies as induction therapy in renal transplantation. MATERIAL AND
      METHODS: Thirty consecutive kidney transplants performed in children 4-16 years
      age in Hospital Infantil La Fe through 1997-2000. The first 15 patients received
      polyclonal antibodies as induction therapy, and 15 consecutive ones received
      monoclonal anti-CD25 antibodies. Receptor, donor and graft characteristics were
      similar in both groups. Also, maintenance immunosuppression was the same.
      RESULTS: The follow-up was over one year in all patients. Four patients in the
      polyclonal antibody group suffered one acute rejection episode and four other
      patients had some drug reaction. In the anti-CD25 treatment group there was one
      episode of acute graft rejection and no collateral effects were observed.
      Glomerular filtration rate, proteinuria, hypertension, infection episodes, graft
      and patient survival were similar in both groups. CONCLUSIONS: Induction therapy
      for pediatric renal transplantation with anti-CD25 antibody has been effective
      and safe. Compared with polyclonal antibodies as standard treatment, basiliximab
      reduced acute rejection episodes and had no collateral side effects. Graft and
      patient one year survival were identical in the two groups.

PMID- 11987688
TI  - [Primary antiphospholipid syndrome diagnosed in hemodialysis].
AB  - We present the next case: male, 30 years old, primary APLA syndrome diagnosed
      after 6 months of treatment with recurrent haemodialysis. The patient, who had a
      history of vascular thrombosis, presented with thrombotic problems in his
      arteriovenous fistula made as vascular access for hemodialysis. The discovery of
      celic trunk and superior mesenteric artery occlusions led us to the clinical
      diagnosis, which was confirmed by presence of a pathological type of lupus
      anticoagulant and anticardiolipin antibodies in plasma. We started treatment with
      oral anticoagulation, warfarin therapy. Since then there have been no more
      thrombotic events, though the period under observation is still short.

PMID- 11987689
TI  - [Massive inferior vena cava thrombosis in a patient with autosomal dominant
      polycystic hepatorenal disease].
AB  - We report a 68-year-old man with autosomal dominant polycystic kidney disease,
      who developed multiple venous thromboses (inferior vena cava, left renal vein and
      iliofemoral veins) caused by local compression of the intrahepatic inferior vena
      cava by hepatic cysts. To our knowledge this is the first reported case of
      inferior vena cava thrombosis caused by hepatic cysts compression. Doppler
      ultrasound, computed tomography, and magnetic resonance imaging were effective in
      documenting the venous thromboses and the underlying lesions non-invasively. Long
      term anticoagulation was an efficient and safe treatment.

PMID- 11987690
TI  - [Multiple brown tumors in a female hemodialyzed patient with severe secondary
      hyperparathyroidism].
AB  - Skeletal brown tumours are relatively uncommon, and brown tumours that involve
      multiple bones are considered very rare. We describe a 29-year-old woman with
      chronic renal failure (CRF) who had undergone hemodialysis for 21 years and
      developed multiple brown tumours associated with severe secondary
      hyperparathyroidism. Computed tomography (CT) revealed multiple brown tumours
      involving scapula, ribs, spine and sacroiliac bone. Microscopic analysis of the
      brown tumour showed dense infiltration of the marrow space by reactive
      fibroblastic tissue with irregularly distributed multinucleated osteoclastic
      giants cells and marked increase in hematopoietic elements.

PMID- 11987691
TI  - [Neurotoxicity after the first dose of oral administration of valaciclovir in a
      female hemodialyzed patient].

PMID- 11987692
TI  - [Renovascular arterial hypertension secondary to polar artery stenosis].

PMID- 11987693
TI  - [Rhabdomyolysis caused by antilipemic agents in a patient with terminal
      nephropathy undergoing continuous ambulatory peritoneal dialysis (CAPD)].

PMID- 11987694
TI  - [Treatment with intravenous iron and infection in hemodialysis].

PMID- 11987695
TI  - [Cases of sudden death after hemodialysis: facts, doubts, and reflexions].

PMID- 11987696
TI  - [Research in public hospitals].

PMID- 11987697
TI  - [Recovery of renal function in patients in a dialysis program].

PMID- 11987698
TI  - [Alpha2-macroglobulin gene polymorphism in patients with Alzheimer's disease].
AB  - Recent studies suggest that alpha 2-macroglobulin (alpha 2 m) may play a role in
      the pathogenesis of Alzheimer's Disease (AD). The presence of alpha 2
      macroglobulin G/G genotype is thought to increase the risk of AD. The aim of the
      study was to analyse alpha 2 m polymorphism in two groups: AD patients (n = 60, F
      = 41, M. = 19, mean age 73.3 +/- 6.3) and non-demented control group (n = 58, F =
      36, M. = 22, mean age 73.1 +/- 8.3, mean MMSE score 27). Frequencies of genotypes
      A/A, A/G, G/G in AD group were: 0.46: 0.42: 0.12. In control group those
      frequencies were: 0.40: 0.48: 0.12. The lack of statistically significant
      difference between G/G frequencies in both groups of patients may suggest that
      alpha 2-macroglobulin G/G genotype is not a risk factor for AD.

PMID- 11987699
TI  - [Patterns of cognitive impairment and apolipoprotein genotype in persons with
      Alzheimer's disease].
AB  - The aim of this study was to test the possible relationship between patterns of
      cognitive deficits--especially impairment of memory processes--and ApoE genotype
      in patients with AD. Fifty seven right-handed subjects (31 males and 26 females)
      were tested in this study. The age of subjects ranged from 50 to 79, the
      education lasted from 11 to 16 years. All subjects were diagnosed as probable AD
      patients on the basis of DSM IV and NINCDS-ADRDA criteria. Each subject was
      examined for: 1) ApoE genotype, 2) general level of activity (GDS and MMSE), 3)
      neuropsychological evaluation of cognitive processes, using full test battery. 37
      patients had at least one of ApoE epsilon 4 allele (e2/4, 3 and 4/4) and 20
      patients had none of ApoE 4 allele (e 2/3 and 3/3). The group of tested subjects
      were subdivided into 2 groups. The first group was comprised by 31 patients with
      3-rd stage (according to GDS) of mental activity. Twenty six patients with 4-th
      stage were included into the second group. Those subgroups did not significantly
      differ if age, education, gender or ApoE allele were considered. Experimental
      data were normalized and then analyzed using a statistical package SPSS/PC+. The
      analysis of variance showed that the type of test, stage of disease and two-way
      interaction ApoE x type of test were highly significant (P < 0.0001). Some
      results were obvious and not surprising (e.g. that results of patients with 4-th
      stage were much worse than the results of patients with stage 3-rd). It turned
      out that the best results were obtained by our patients in naming tests, the
      worst--in learning test with distraction. Patients with ApoE epsilon 4 performed
      better than patients with none ApoE epsilon 4 in the Rey's test, in the
      similarity test and in the test which required repeating numbers starting from
      the last one. The differences between the subgroups of patients with different
      ApoE alleles were confirmed by different distributions of correlations. All
      statistical analyses were repeated for more homogenous group of patients (only
      with stage 3-rd). The pattern of results resembled the previous one (i.e. better
      performance in the same tests) with one exception: additionally, in delayed
      recall test patients with none ApoE epsilon 4 performed much better that ApoE
      epsilon 4. Our results showed that some cognitive processes depended on ApoE
      genotype. Patients with none ApoE epsilon 4 genotype had less severe deficits in
      delayed recall of new information. On the other hand, working memory appeared to
      be less affected in patients with ApoE epsilon 4 genotype. Independent of
      genotype, both group showed similar impairment of learning ability without
      deficits in remote memory.

PMID- 11987700
TI  - [Matrix metalloproteinase-9 (MMP-9) activity in cerebrospinal fluid of
      amyotrophic lateral sclerosis patients].
AB  - Matrix metalloproteinase-9 (MMP-9) is a member of the family of zinc-dependent
      endopeptidases that degrade extracellular matrix proteins. It can be activated by
      serine proteinases or by superoxide radicals. The motor neurons in amyotrophic
      lateral sclerosis patients express significantly higher levels of MMP-9,
      suggesting a role in neurodegeneration. The aim of the study was to investigate
      MMP-9 in cerebrospinal fluid from amyotrophic lateral sclerosis patients. MMP-9
      was measured by enzyme-linked immunosorbent assay ELISA in cerebrospinal fluid
      from 24 amyotrophic lateral sclerosis patients and 15 controls. The mean
      amyotrophic lateral sclerosis duration was 18 months. According to Munsat ALS
      Health State Scale, the patients were divided into four groups: mild, moderate,
      severe, terminal. The patients were also divided into groups with shorter (below
      12 months) and longer (above 12 months) duration of the disease. MMP-9 level was
      insignificantly lower in the cerebrospinal fluid from amyotrophic lateral
      sclerosis patients compared with controls. MMP-9 level showed a tendency to
      decrease with clinical status worsening, however this correlation was not
      statistically significant. The difference between MMP-9 level in the
      cerebrospinal fluid between the groups of patients with shorter and longer
      duration of amyotrophic lateral sclerosis was not significant.

PMID- 11987701
TI  - [Alternative medicine methods applied in patients before surgical treatment of
      lumbar discopathy].
AB  - Case records of 200 patients operated on in 1998/99 for herniated lumbar disc in
      Neurosurgery Dept. showed that 95 patients (47.5%) had been treated previously by
      148 alternative medical or non-medical procedures. The authors discuss the
      problem of non-conventional treatment methods applied for herniated lumbar disc
      by professionals or non professionals. The procedures are often dangerous.

PMID- 11987702
TI  - [Retrospective assessment of bilateral trigeminal neuralgia treatment].
AB  - Bilateral trigeminal neuralgia is a rarely observed suffering. It is usually
      localised on one half of the face and few years after therapy or idiopathic
      regression it appears on the other side. In exceptional cases trigeminal
      neuralgia appears on both sides at the same time. Neurovascular decompression or
      neurotomy in the pontocerebellar angle are the most effective therapy. In the
      last 25 years of 257 surgically treated patients with trigeminal neuralgia
      bilateral pain was found in 12 cases (5%). Retrospective assessment of the used
      method, in our department, in the treatment of trigeminal neuralgia demonstrated
      efficacy of this procedure.

PMID- 11987703
TI  - [Vascular endothelial growth factor expression in cerebral neoplasms].
AB  - Angiogenesis plays an important role in growth of neoplasm. Among a variety of
      proangiogenic agents, vascular endothelial growth factor (VEGF) is regarded as a
      crucial mediator of tumour angiogenesis. It acts in a paracrine way through the
      receptors localised in endothelial cells. Many authors maintain that rich
      vasculature of the neoplasm is associated with its malignant nature. The aim of
      this study was to examine the relations between expression of VEGF and features
      of malignancy of brain tumours. Sixty-seven samples of brain tumours were
      examined: 17 meningiomas, 34 gliomas and 16 metastases to the central nervous
      system. Expression of VEGF was estimated by radioimmune assay. The authors
      confirmed the presence of this factor in all types of tumours but the highest
      concentration of VEGF was found in high-grade gliomas.

PMID- 11987704
TI  - [Acrylic bone cement use for internal spondylodesis in neurosurgical operations].
AB  - Vertebral column stabilization relying on performing of surgical internal
      spondylodesis with acrylic bone cement (methylmethacrylate, MMA) was carried out
      in 27 cases treated surgically in Department and Clinic of Neurosurgery in Poznan
      from 1996 to 1999. The age of patients was 16-69 (mean age 50.29 +/- 15.29)
      years. Male patients predominated (2:1). The vertebral lesion was caused by
      neoplasm (55% of cases), degenerative disease (26%), trauma (19%). Pathological
      changes were found in cervical region in 16 (59%), in thoracic region in 6 (22%)
      and in lumbar region in 5 (19%) patients. The anterior surgical approach to
      vertebral column was chosen in 17 (63%), posterolateral approach in 8 (30%) and
      posterior approach in 2 (7%) patients. Bone acrylic cement was used for
      reconstruction of vertebral body damaged by neoplasm or trauma, whereas it
      substituted the removed intervertebral disc or vertebral body in degenerative
      diseases. The acrylic cement graft in all cases maintained the proper anterior
      and medial vertebral column alignment. Semiliquid acrylic cement was used for
      filling of defects after tumour removal in thoracic and lumbar vertebral bodies.
      Acrylic cement graft was properly prepared in cuboid form and was inserted into
      the intervertebral spaces in patients with trauma or degenerative diseases. In
      all cases involving bone acrylic cement, stabilization of the vertebral segment
      was completed by metallic implants (cervical plates, "Z" plates, intrapedicular
      screws and rods). No postoperative complications (wound infections or implant
      dislocation) were observed. Postoperative, neurological signs were intensified in
      3 cases (12%) and were regressive. Mortality rate was 4%. This type of internal
      spondylodesis makes possible to restore the anterior and medial columns and
      immobilisation of the proper vertebral segments.

PMID- 11987705
TI  - [Common carotid artery intima-media thickness: the role in evaluation of
      atherosclerosis progression].
AB  - Atherosclerosis is a generalized vascular disease. There are methods to
      investigate the development of atherosclerosis. Doppler ultrasonography is a
      noninvasive and safe method. By this method we can see and measure the first
      stage of atherosclerosis development--thickening of intima-media complex.
      Measuring intima-media thickness of common carotid artery may be used as an
      indicator of generalized atherosclerosis. Intima-media thickness is also used to
      study progression of atherosclerosis and its possible regression during therapy.

PMID- 11987706
TI  - [Gene therapy in neurological diseases].
AB  - Gene therapy is a new therapeutic method which uses molecular biology techniques
      to modulate expression of genes involved in disease pathogenesis. Gene therapy
      has evolved rapidly in the last ten years. In that time several experimental
      models of metabolic and degenerative neurological disorders, brain tumours,
      stroke, epilepsy, motor neuron disease, multiple sclerosis and muscle dystrophy
      were treated with some positive results by gene therapy techniques. The first
      clinical trials are currently ongoing in certain metabolic diseases, brain
      tumours and limb girdle dystrophy. DNA vaccination is also used in clinical
      trials. It seems that gene therapy will become soon the alternative method of
      treatment of those neurological diseases where current methods of treatment are
      not effective.

PMID- 11987707
TI  - [Cerebral aneurysms and current methods of treatment].
AB  - The authors discuss briefly aneurysms cerebral arteries. In the light of the
      pertinent literature the hypotheses of their development are reviewed. These
      aneurysms are probably lesions acquired by individuals with special
      predispositions, acquired or inborn. The problems of aneurysm diagnosis are
      reviewed and the methods are discussed of their management, both surgical and
      intravascular (embolization). Both methods are tentatively compared. In certain
      cases each method may be an excellent alternative for the other, and in other
      cases they are mutually complementary extending thus the range of therapeutic
      possibilities.

PMID- 11987708
TI  - [Camptocormia, a rare form of motor system disorders in Parkinson's disease].
AB  - Camptocormia is characterized by pronounced forward flexion of the thoracolumbar
      spine, which increases while walking and disappears in recumbent position. The
      clinical spectrum of the described disorders with concomitant camptocormia is
      heterogenous. It was described for the first time in idiopathic Parkinson's
      disease in 1999. The pathophysiology of this phenomenon remains unclear but seems
      to be not related to antiparkinsonian treatment. The authors present the case of
      a 54 years old woman, with idiopathic Parkinson disease diagnosed 5 years ago.
      The rapid progression of the disease was associated with good response to
      Levodopa therapy, although the dose had to be increased up to 1400 mg/d (with
      peripheral decarboxylase and COMT inhibitor). After 5 years she developed painful
      spasms of paraspinal muscles which resulted in trunk flexion. The clinical
      picture resembled the described cases of camptocormia. There was no correlation
      between the appearance of camptocormia and the regime of levodopa administration
      (time or dosage). Therefore, one can conclude, that presumably camptocormia is
      not a form of dystonia of the trunk but, the result of till now unclear other
      factors (dysfunction in other non-dopaminergic nigrostriatal projections?).

PMID- 11987709
TI  - [Pseudochoreoathetosis as manifestation of cervical cord lesion. Case report].
AB  - The involuntary movements of choreoathetotic type are commonly regarded as a sign
      of basal ganglia lesion. However, such movements can also occur in pathological
      processes involving the cervical spinal cord. This condition is referred to as
      pseudochoreoathetosis. Involuntary movements can be related to lack of proper
      coordination between agonist and antagonist muscles, their simultaneous
      activation due to impairment of reciprocal inhibition. The characteristic feature
      of pseudochoreoathetosis is proprioceptive sensory loss. In this paper we present
      4 patients who developed various involuntary limb movements in early stage of the
      disease. Lesions in the cervical spinal cord were confirmed by MRI. In case 1 the
      cause was astrocytoma, in cases 2 and 3--demyelination, in case 4 the precise
      character of the lesion could not be established. Pseudochoreoathetosis is a rare
      condition which often remains unrecognized. The presented cases emphasise the
      importance of early and correct diagnosis leading to proper therapeutical
      procedure.

PMID- 11987710
TI  - [Embolitic material (coils) dislocation inside a giant and cerebral aneurysm and
      morphological aneurysm changes after coiling. Case report].
AB  - The placement of tungsten coils into aneurysm sack in patient after SAH is a
      method of treatment used in many neurosurgical departments. The main indications
      for coiling procedures are severe neurological status (IV i V according to WFNS)
      and posterior circulation aneurysms. Coiling can be offered to a patient who does
      not agree to clipping procedure. The presented case is a patient with a giant MCA
      aneurysm who did not agree to clipping procedure and, therefore, was subjected to
      coiling. During the follow-up of 2 months; control skull X-rays and after them
      control angiography were performed to monitor coils arrangement in the aneurysm
      sack and their possible dislocation. The control angiography after 6 months
      showed significant enlargement of the aneurysm. The aneurysm was clipped, totally
      excised and subjected to histopathological examination. It was found that the
      material inside the aneurysm sack can change its shape due to the impact of the
      flowing blood (change in the coil shape, resorption and the recanalization of the
      clot) similarly to the natural process of aneurysm development. Morphological
      changes of the aneurysm appear to be also possible in spite of the thrombus
      formation in the aneurysm sack.

PMID- 11987711
TI  - [Revascularisation after encephalo-duro-arterio-synangiosis. Case report].
AB  - In surgical treatment was performed of patients after cerebral ischaemic stroke
      and cerebral ischaemia. The authors applied the surgical technique of indirect
      anastomosis (EDAS-encephalo-duro-arterio synangiosis). The Japanese authors
      described this method first as a treatment for moya-moya disease. The
      acetazolamid (Diamox) test and clinical symptoms were the main criteria to
      perform this surgical procedure. All patient with abnormal Diamox test were
      treated surgically. After 6 months control angiography was performed to visualize
      a new network of vessels near the main vessel (superficial temporal artery).

PMID- 11987712
TI  - [Anterior interbody fusion of cervical spine with case-plate PCB].
AB  - Two cases with cervical discopathy and radiculopathy are presented. Discectomy
      and anterior interbody fusion with cage-plate PCB manufactured by French company
      Scient'x was performed. Authors present the shape of the implant and technical
      details of implantation. The paper discusses the advantages of the PCB which
      simplifies and shortens the operation procedure, minimizes the risk of
      traditional bone graft harvesting and provides immediate stabilization of the
      operated segment.

PMID- 11987713
TI  - [Surgical treatment of Parkinson's disease in Poland in the last century].
AB  - Surgery of Parkinson's disease started in the middle of the last century. At the
      same time this treatment was introduced in Poland. Chorobski removed Broadsman's
      area 4 through craniotomy. In 1961 Liszka in Krakow introduced the stereotactic
      procedures, thalamo- and pallidotomy. This type of surgery was soon introduced in
      two other neurosurgical centers. For the next several years treatment was mostly
      pharmacological. However, stereotactic treatment was used in patients poorly
      tolerating drugs. In the meantime first attempts were made at implantation of
      fetal substantia nigra, with good results. At the end of the century in several
      patients electrostimulators were implanted. In the last century all known methods
      of surgical treatment were applied in Poland.

PMID- 11987714
TI  - [Clinical picture of spinocerebellar ataxia type I (SCA1)].
AB  - Spinocerebellar ataxia is a group of diseases with autosomal dominant inheritance
      heterogenous both clinically and genetically. So called dynamic mutations
      underlie most these nosological units. The clinical patterns of various SCA types
      have not yet been defined completely. The purpose of the present report was
      description of the typical symptoms and signs of type 1 SCA. Seventeen patients
      from 13 families (M-2, F-15) were studied clinically in detail. The diagnosis was
      confirmed by DNA analysis. The assessment included neurological status, cognitive
      functions, the results of EEG, EMG, SEP, VEP, BAER and MRI examinations. The
      pedigrees indicated autosomal dominant inheritance pattern. The mean age at onset
      was 35.5 +/- 6.8 years (range 23-45 years) and it suggested negative correlation
      with the number of CAG repetitions. Cerebellar syndrome limb and truncal, ataxia
      and dysarthria was present in all cases. Six patients had nystagmus, 3 had slow
      saccades, 2 had gaze limitation upward, and lateral and 6 had dysphagia. Signs of
      pyramidal system involvement were found in 10 cases, one had athetotic movements,
      one had orthostatic hypotension. Two patients had dementia features, 9 had some
      decline of intellectual functions, mainly with difficulties of memorization,
      learning and concentration. In 16 cases MRI demonstrated vermis atrophy and
      atrophy of cerebellar hemispheres, 14 had fourth ventricle dilatation, 8 had
      flattening of pons base, 8 had narrowing of cervical spinal cord, 8 had dilated
      CSF spaces over frontal lobes and in 6 cases lateral ventricles were dilated.
      Electrophysiological peripheral nervous system investigations showed in 16 cases
      long-standing damage to the motor and sensory peripheral neurons at the level of
      nerve trunks, more pronounced in sensory nerves. In 13 cases peripheral neuron
      damage was subclinical. SEP showed in all patients disturbed function of
      ascending sensory pathways at peripheral and spinocortical levels.

PMID- 11987715
TI  - Management of the student with food allergies in school.

PMID- 11987716
TI  - School nursing in the state of Georgia.

PMID- 11987717
TI  - Poverty: a framework for understanding and working with students and adults from
      poverty.

PMID- 11987718
TI  - Measuring our progress (or NASN's Healthy People report card).

PMID- 11987719
TI  - First-ever report on trends in protecting children's health: EPA Press release,
      1/8/01.

PMID- 11987720
TI  - Tell your stories ... spread your healing presence. An interview with Julia
      Balzer Riley, MN RN.

PMID- 11987721
TI  - Parent-friendly health information.

PMID- 11987722
TI  - Prepare for spring: teach prevention.

PMID- 11987723
TI  - MNA health care survey results released during convention.

PMID- 11987724
TI  - Forces surrounding the use of standardized nursing language.

PMID- 11987725
TI  - Rise to the stars!

PMID- 11987726
TI  - Nurses at Pearl Harbor. The real story....

PMID- 11987727
TI  - Nursing regulation in Southeast Asia and the Western Pacific. A regional
      initiative.

PMID- 11987728
TI  - Regulation of registered nursing. The Canadian perspective.

PMID- 11987729
TI  - Regulation of registered nursing. The American perspective.

PMID- 11987730
TI  - Russian Red Cross visiting nurses. Quietly caring for the invisible members of
      society.

PMID- 11987731
TI  - Social support as TLC: the great elixir.

PMID- 11987732
TI  - Courage and the new frontier.

PMID- 11987733
TI  - Importance of simultaneous binaural bithermal caloric testing.

PMID- 11987734
TI  - Laterally positioned mucocele of the frontal sinus.

PMID- 11987735
TI  - Inferior glottic ridges that prevent vocal fold closure.

PMID- 11987736
TI  - Electronystagmography in a patient who could not drive more than 5 minutes at
      highway speeds.

PMID- 11987737
TI  - Cholesterol granuloma of the petrous apex.

PMID- 11987738
TI  - Stevens-Johnson syndrome with diffuse esophageal involvement.

PMID- 11987739
TI  - Airway management of the severely retrognathic child: use of the laryngeal mask
      airway.
AB  - Successful airway management of an infant or child with moderate to severe
      retrognathia first requires recognition of a potential problem. If the child
      cannot be intubated in a standard fashion, the use of a laryngeal mask airway
      (LMA) should be considered. We describe two cases wherein a toddler and an infant
      with severe retrognathia failed multiple attempts at traditional intubation. Both
      had an anterior larynx and hypoplasia of the mandible. In both cases, a
      subsequent LMA was successfully placed. The severely retrognathic newborn or
      child presents to the physician a unique challenge in airway management.
      Techniques to manage this difficult pediatric airway are different from those
      used in the adult. Otolaryngologists should be aware of this intubation technique
      and include it in their armamentarium of airway-management strategies. The LMA is
      not recommended as the technique of choice for securing a difficult airway, but
      it is an effective alternative when indicated, and it might be life-saving.

PMID- 11987740
TI  - Recent results with the MED-EL COMBI 40+ cochlear implant and TEMPO+ behind-the
      ear processor.
AB  - Cochlear implantation is a viable treatment for patients with severe to profound
      hearing loss. We report the results of speech perception tests (numbers,
      monosyllables, and sentence tests) achieved with MED-EL's COMBI40+ (C40+)
      cochlear implant after 12 months of use. These findings, which were taken from a
      larger German study, were similar to those of other studies of the C40+ implant.
      We also compared the differences in speech perception observed with the CIS PRO+
      body-worn speech processor and the newer TEMPO+ behind-the-ear speech processor.
      Although these results were similar with respect to most of the measured
      parameters, the TEMPO+ processor had a distinct advantage during tests in noise.

PMID- 11987741
TI  - Bilateral Lemierre's syndrome: a case report and literature review.
AB  - Lemierre's syndrome is characterized by thrombosis of the internal jugular vein
      that develops following an oropharyngeal infection. Sepsis and septic metastases
      frequently ensue and affect the lungs, the musculoskeletal system, and
      occasionally the liver. Most cases are caused by infection with Fusobacterium
      necrophorum. This infection responds to antibiotic therapy with beta-lactamase
      resistant compounds that exert good anaerobic coverage. Anticoagulation and
      surgical intervention can be helpful in advanced cases. Fewer than 160 cases of
      classic Lemierre's syndrome have been described; approximately one-third of these
      reported cases have occurred since 1988. We describe a new case of Lemierre's
      syndrome that occurred in an otherwise healthy 27-year-old man. Thrombosis of
      both internal jugular veins extended through the subclavian system and into both
      upper extremities. The patient was treated with intravenous antibiotics and
      heparin during 14 days of hospitalization. He was discharged on oral clindamycin
      and warfarin sodium, and after 6 months he was able to return to full activity.
      To our knowledge, this is the first reported case of Lemierre's syndrome in which
      internal jugular vein thrombosis occurred bilaterally. By reporting this
      previously undescribed manifestation of Lemierre's syndrome, we hope to increase
      practitioner awareness of this disease entity.

PMID- 11987742
TI  - Basaloid squamous cell carcinoma of the larynx: report of a case.
AB  - Basaloid squamous cell carcinoma is a variant of squamous cell carcinoma. This
      malignancy has a predilection for the upper aerodigestive tract, although it has
      been found in multiple other sites. The tumor is highly aggressive biologically,
      and the overall prognosis is poor despite intensive treatment. We describe a case
      of basaloid squamous cell carcinoma of the larynx that metastasized to the spine.

PMID- 11987743
TI  - Aortobronchial fistula: a rare etiology for hemoptysis.
AB  - Aortobronchial fistula is an extremely rare cause of hemoptysis. Aortobronchial
      fistula occurs in patients who have a history of thoracic vascular surgery.
      Because its symptoms are nonspecific, a high index of suspicion is critical if
      the physician is to detect it. The results of imaging studies (e.g., plain films,
      computed tomography, and angiography) and bronchoscopy are sometimes, but not
      always, diagnostic--another reason the diagnosis is difficult. Left untreated,
      mortality in patients with aortobronchial fistula is 100%. Patients can be
      salvaged by a variety of techniques, including the placement of an endovascular
      stent. We describe the case of a 52-year-old man who came to us with hoarseness
      and hemoptysis, which proved to be underlying symptoms of aortobronchial fistula.
      He was treated successfully.

PMID- 11987744
TI  - Magnetic resonance imaging in the diagnosis of subglottic cysts of infancy: case
      report and review.
AB  - Subglottic cysts can cause stridor and respiratory distress in the infant. The
      diagnosis of subglottic cysts is often confirmed during direct laryngoscopy and
      bronchoscopy. We describe the case of a 6-month-old boy with bilateral subglottic
      cysts that were preoperatively diagnosed by magnetic resonance imaging (MRI). We
      also review the current literature on the diagnosis and treatment of subglottic
      cysts. Up until now, 63 cases of subglottic cysts were reported in the literature
      since 1966, and most were diagnosed by direct endoscopy. In this article, we
      describe a new case and we provide the first published report of the novel use of
      MRI in diagnosing this lesion.

PMID- 11987745
TI  - G-induced vestibular dysfunction ('the wobblies') among aerobatic pilots: a case
      report and review.
AB  - G-induced vestibular dysfunction (GIVD) is a condition well known to aircraft
      pilots who experience high positive and negative G loads during unlimited
      aerobatic competitions and air-show demonstrations. After landing and walking
      from their aircraft, pilots with GIVD manifest an extremely unstable gait, which
      they call the wobblies. This article includes a report of one such case of GIVD,
      which to the author's knowledge is the first published case report of this
      condition in the medical literature. The author also discusses what is known and
      theorized about the pathogenesis of GIVD, and he reviews its diagnosis,
      treatment, and prevention.

PMID- 11987746
TI  - Congenital absence of the incus bilaterally without other otologic anomalies: a
      new case report.
AB  - We describe only the third reported case of congenital, bilaterally absent
      includes that were not accompanied by another otologic abnormality. This
      condition was detected in a 3-year-old boy who was being evaluated for a hearing
      impairment and speech and language delay. The patient was treated with partial
      ossicular replacement prostheses, which resulted in an improvement in his
      hearing.

PMID- 11987747
TI  - Cellular schwannoma of the paranasal sinuses: initial report of a case.
AB  - Cellular schwannomas are a benign variant of classic schwannomas. Their
      histologic appearance closely mimics that of malignant peripheral nerve-sheath
      tumors, which are high-grade sarcomas. In this article, we describe what to our
      knowledge is the first reported case of a cellular schwannoma of the paranasal
      sinuses and only the 33rd reported case of any schwannoma at this site. We also
      discuss the histology and management of cellular schwannomas and review the
      pertinent literature.

PMID- 11987748
TI  - Practical approaches to protein formulation development.

PMID- 11987749
TI  - Rational design of stable lyophilized protein formulations: theory and practice.

PMID- 11987750
TI  - Spray-drying of proteins.

PMID- 11987751
TI  - Surfactant-protein interactions.

PMID- 11987752
TI  - High throughput formulation: strategies for rapid development of stable protein
      products.

PMID- 11987753
TI  - Recombinant production of native proteins from Escherichia coli.

PMID- 11987754
TI  - Physical stabilization of proteins in aqueous solution.

PMID- 11987755
TI  - Effects of conformation on the chemical stability of pharmaceutically relevant
      polypeptides.
AB  - Control of chemical instability in protein pharmaceuticals continues to be a
      critical issue in developing stable formulations. While the effects of pH, buffer
      composition, ionic strength and temperature remain the most effective methods for
      controlling hydrolysis and oxidation reactions, it appears that conformational
      control may also be important. Addition of excipients to maintain native
      structure and reduce the propensity of the protein to denature and/or aggregate
      is already a central theme in stabilizing proteins (Arakawa et al., 1993). The
      same additives have now been found to slow both deamidation and oxidation,
      whether in solution or in the solid state. What is emerging is an additional
      approach for producing protein pharmaceuticals that maintain native structure and
      activity during long-term storage.

PMID- 11987758
TI  - ANA survey produces startling information.

PMID- 11987757
TI  - Bringing a voice to the "silent" impact.

PMID- 11987759
TI  - FAQs about nurse practitioners.

PMID- 11987760
TI  - Caring is a skill.

PMID- 11987761
TI  - Whistleblower legislation: what you need to know.

PMID- 11987762
TI  - Differential diagnosis in chronic diffuse infiltrative lung disease on high
      resolution computed tomography.

PMID- 11987763
TI  - Radiology of acute diffuse lung disease in the immunocompetent host.

PMID- 11987764
TI  - Case of the season. Foramen of Morgagni hernia.

PMID- 11987765
TI  - Diffuse lung disease in the immunocompromised non-HIV patient.
AB  - Physicians are encountering an increasing number of patients with various levels
      of immunosuppression, such as patients with AIDS, transplant recipients, patients
      on immunosuppressive therapy, and those with congenital immune defects and
      malignancy. This results in a greater diagnostic dilemma for the medical
      community because of the significant increased risk of opportunistic infections
      and noninfectious complications, as well as a more aggressive clinical course
      with typical pathogens. [figure: see text] Furthermore, it is not just the
      pathogens that are changing but also their clinical and radiographic
      presentations. The radiologist has a large role in not only detecting the
      presence of disease but also in narrowing the differential possibilities. This
      can be an overwhelming task given the wide variety of presentations of diseases
      on radiographs. However, by understanding the level and degree of the patient's
      immunosuppression, the radiologist may anticipate the most likely pulmonary
      complications. By using the radiographic morphology, distribution, and temporal
      evolution of the abnormalities, a manageable differential diagnosis can be
      created for referring clinicians.

PMID- 11987766
TI  - High-resolution computed tomography: technique and pitfalls.

PMID- 11987767
TI  - Update on lung disease in AIDS.
AB  - Pulmonary disorders remain an important complication of HIV infection, even in
      the current era of potent antiretroviral therapy. Using an integrated approach
      that combines radiographic pattern recognition with knowledge of a patient's
      clinical symptoms, laboratory data, immune status level, demographic information,
      and drug therapy can enhance the interpretation of imaging studies in HIV
      infected patients. Although chest radiography remains the mainstay of imaging the
      HIV-positive patient with respiratory symptoms, CT plays an increasingly
      important secondary role in selected cases.

PMID- 11987769
TI  - Imaging features of thoracic sarcoidosis.

PMID- 11987768
TI  - Drug-induced lung injury.
AB  - Lung injury is an increasing cause of morbidity and mortality in patients treated
      with cytotoxic and noncytotoxic drugs. Prompt diagnosis is important because
      early drug-induced lung injury will often regress with the cessation of therapy.
      Diagnosis requires a high index of suspicion because infection, radiation
      pneumonitis, and recurrence of the underlying disease can manifest clinically and
      radiologically in a similar manner. Because the lungs have only a limited number
      of histopathologic responses to injury, including pulmonary edema/diffuse
      alveolar damage, NSIP, BOOP, EP, and pulmonary hemorrhage, knowledge of these
      manifestations and the corresponding radiologic manifestations can often be
      useful in suggesting a diagnosis of drug-induced lung injury. An understanding of
      the drugs most commonly associated with lung injury can also facilitate
      diagnosis.

PMID- 11987770
TI  - Poly-L-lysine-based gene delivery systems. Synthesis, purification, and
      application.

PMID- 11987771
TI  - Regulated expression of plasmid-based gene therapies.

PMID- 11987772
TI  - Photochemical transfection. Light-induced, site-directed gene delivery.

PMID- 11987773
TI  - Direct gene transfer and vaccination via skin transfection using a gene gun.

PMID- 11987774
TI  - Preparation of pseudotyped retroviral vector.

PMID- 11987775
TI  - Targeted gene transfer to liver using protein-DNA complexes.

PMID- 11987776
TI  - Quantitative measurement of the concentration of active recombinant retrovirus.

PMID- 11987777
TI  - Minigene-containing retroviral vectors using an alphavirus/retrovirus hybrid
      vector system. Production and use.

PMID- 11987778
TI  - Retrovirus-mediated gene transfer to human hematopoietic stem cells.

PMID- 11987779
TI  - Genetically modified skin substitutes. Preparation and use.

PMID- 11987780
TI  - Bioartificial muscles in gene therapy.

PMID- 11987781
TI  - Cytokine gene-modified cell-based cancer vaccines.

PMID- 11987782
TI  - Receptor-directed molecular conjugates for gene transfer.

PMID- 11987783
TI  - HIV-based vectors. Preparation and use.

PMID- 11987784
TI  - Packaging cell system for lentivirus vectors. Preparation and use.

PMID- 11987785
TI  - Lentiviral vectors. Preparation and use.

PMID- 11987786
TI  - Simian foamy virus vectors. Preparation and use.

PMID- 11987787
TI  - Recombinant feline immunodeficiency virus vectors. Preparation and use.

PMID- 11987788
TI  - Lentivirus vector based on simian immunodeficiency virus. Development and use.

PMID- 11987789
TI  - Cytoplasmic RNA vector derived from nontransmissible Sendai virus. Production and
      use.

PMID- 11987790
TI  - Preparation of helper-dependent adenoviral vectors.

PMID- 11987791
TI  - Construction of first-generation adenoviral vectors.

PMID- 11987792
TI  - Preparation of ovine adenovirus vectors.

PMID- 11987793
TI  - Highly purified recombinant adeno-associated virus vectors. Preparation and
      quantitation.

PMID- 11987794
TI  - High-titer stocks of adeno-associated virus from replicating amplicons and herpes
      vectors.

PMID- 11987795
TI  - Herpes simplex virus/adeno-associated virus hybrid vectors for gene transfer to
      neurons. Preparation and use.

PMID- 11987796
TI  - Development of replication-defective herpes simplex virus vectors.

PMID- 11987797
TI  - Gene transfer into muscle by electroporation in vivo.

PMID- 11987798
TI  - Viral liposomes. Preparation and use.

PMID- 11987799
TI  - LPD nanoparticles--novel nonviral vector for efficient gene delivery.

PMID- 11987800
TI  - Solvoplex synthetic vector for intrapulmonary gene delivery. Preparation and use.

PMID- 11987801
TI  - Gene correction frequency by chimeric RNA-DNA oligonucleotide using nuclear
      extracts.

PMID- 11987802
TI  - Molecular phylogeny of the arenaviruses.

PMID- 11987803
TI  - Receptor structure, binding, and cell entry of arenaviruses.

PMID- 11987804
TI  - Arenaviruses: genomic RNAs, transcription, and replication.

PMID- 11987805
TI  - Arenaviruses: protein structure and function.

PMID- 11987806
TI  - Reverse genetics of arenaviruses.

PMID- 11987807
TI  - Mammalian reservoirs of arenaviruses.

PMID- 11987808
TI  - Human infection with arenaviruses in the Americas.

PMID- 11987809
TI  - Lassa fever.

PMID- 11987810
TI  - Arenaviruses. I. The epidemiology molecular and cell biology of arenaviruses.
      Introduction.

PMID- 11987811
TI  - Lymphocytic choriomeningitis virus and immunology.

PMID- 11987812
TI  - Contribution of LCMV transgenic models to understanding T lymphocyte development,
      activation, tolerance, and autoimmunity.

PMID- 11987813
TI  - Regulation of virally induced autoimmunity and immunopathology: contribution of
      LCMV transgenic models to understanding autoimmune insulin-dependent diabetes
      mellitus.

PMID- 11987814
TI  - LCMV and the central nervous system: uncovering basic principles of CNS
      physiology and virus-induced disease.

PMID- 11987815
TI  - Contribution of LCMV towards deciphering biology of quasispecies in vivo.

PMID- 11987816
TI  - Designing arenaviral vaccines.

PMID- 11987817
TI  - Junin virus vaccines.

PMID- 11987818
TI  - Bystander T cell activation and attrition.

PMID- 11987819
TI  - Immunocytotherapy.

PMID- 11987820
TI  - Mechanisms of humoral immunity explored through studies of LCMV infection.

PMID- 11987821
TI  - Innate immune responses to LCMV infections: natural killer cells and cytokines.
AB  - Although much remains to be learned, the study of early responses to LCMV
      infections of mice has contributed to the basic understanding of the regulation
      of a variety of important innate immune responses. Major discoveries have
      included the appreciation of the levels of type 1 IFNs induced during endogenous
      responses to viral infections, the importance of IFN-alpha/beta for induction of
      NK cell cytotoxicity, and the roles for IFN-alpha/beta in regulating the
      expression of other innate cytokines, i.e., IL-12 and IFN-gamma produced by NK
      cells (Fig. 11). Taken together with the characterization of adaptive responses
      to LCMV, a paradigm is emerging for a possible initial to innate to adaptive
      response cascade during infections with viruses eliciting endogenous expression
      of high levels of IFN-alpha/beta. The results not only advance the understanding
      of endogenous responses to viral infections and how they are balanced to achieve
      the best possible outcome for the host, but also give insights into possible
      consequences of therapeutic intervention with type 1 IFNs.

PMID- 11987822
TI  - Biology and pathogenesis of lymphocytic choriomeningitis virus infection.

PMID- 11987823
TI  - Arenaviruses. II. The molecular pathogenesis of arenavirus infections.
      Introduction.

PMID- 11987824
TI  - Phospholipase D-structure, regulation and function.

PMID- 11987825
TI  - The structural basis of G-protein-coupled receptor function and dysfunction in
      human diseases.

PMID- 11987826
TI  - Endotoxin tolerance-mechanisms and beneficial effects in bacterial infection.

PMID- 11987827
TI  - [Therapeutic angiogenesis for coronary artery disease. Contemporary results and
      perspectives].
AB  - Therapeutic angiogenesis is referred to as development of new vasculature caused
      by various therapeutic measures such as: gene therapy, growth factors,
      percutaneous and transmyocardial laser revascularization. The scope of the
      current article is to provide review of performed clinical trials using
      therapeutic angiogenesis in patients with coronary artery disease.

PMID- 11987828
TI  - [Mast cells and atherosclerosis].
AB  - Recent data indicate an important role of mast cell in the pathogenesis of
      atherosclerosis; especially the influence of biologically active substances
      derived from mast cells such as serine proteinases on metabolism of angiotensin,
      bradykinin and lipoproteins. The presence of mastocytes in the hinge region of
      atherosclerotic plaque seems to indicate their important role in plaque rupture
      and complications of fibrous plaque. Besides the many pathogenic effects of
      mastocytes they may participate in the maintenance of vascular wall integrity and
      regeneration. This article presents important aspects of the role of mast cells
      in pathogenesis of atherosclerosis.

PMID- 11987829
TI  - [Histocompatibility HLA system of man. Considerations in the light of current
      concepts. VII. Nonclassical HLA- E, F, and H loci].
AB  - Current opinions connected with HLA-E and HLA-F genes determining "nonclassical"
      (HLA-Ib) class I antigens of the Main Histocompatibility Complex MHC, and formed
      in the consequence of mutation or partial deletion of HLA-H pseudogene loci were
      presented. The expression of protein products of HLA-E and -F genes on some cells
      and tissues, their polymorphism, and also their biological functions in organisms
      were qualified by the use of molecular technics. The kind and frequency of
      occurrence of mutations 845 A (C282Y) and 187 G (H63D) in gene HLA-H were
      analysed, and in this context some genetic aspects of hereditary hemochromatozy
      (HH) were discussed.

PMID- 11987830
TI  - [A case of cor triatriatum in a 65-year old male with atrial tachycardia].
AB  - We present a case of asymptomatic cor triatriatum in a 65-year old male with
      atrial tachycardia.

PMID- 11987831
TI  - [Successful RF ablation in a patient with paroxysmal atrial fibrillation induces
      by atrioventricular nodal reentrant tachycardia].
AB  - We describe a case of 47-year old patient with frequent episodes of paroxysmal
      atrial fibrillation (PAF) with fast ventricular rate. During electrophysiological
      study an atrioventricular nodal reentrant tachycardia (AVNRT) was diagnosed with
      rapid degeneration into atrial fibrillation. Successful RF ablation of slow
      pathway was performed. There were no PAF recurrences during six months follow-up.

PMID- 11987832
TI  - [Foreign body in the right frontal lobe of the brain as a result of right eyeball
      and right eye-socket trauma--case report].
AB  - We report a case of a 44 year old man, who was admitted to our hospital because
      of right eyeball and right eye-socket due to a piece of diamond circular saw.
      Right eyeball was sutured. CT--examination showed a metallic foreign body in the
      right frontal lobe of brain. Metallic foreign body, which damaged the right
      eyeball, caused upper restriction of right eye-socket ceiling and stuck in a
      frontal lobe of the brain was removed.

PMID- 11987833
TI  - [Medical Academy of Lodz during the Stalinist period (1949-1953)].
AB  - During the Stalinist period especially between 1949-1953 the Medical Academy in
      Lodz was under constant ideological pressure of the Communist Party (PZPR). It
      was trying to stir-up students and workers in the spirit of marxist and the
      leninist ideology. The main PZPR's methods of influence were to reduce and
      importunate indoctrination. They exterminated all impulses of protest and
      opposition, also they investigated and penetrated academic life. On admission to
      the university, countryman and workman youth was preferred. People who had
      different conviction and opinion were removed. On every step the party's
      authority was flatten in the face of Soviet's dictate.

PMID- 11987834
TI  - [Krakow Program for Secondary Prevention of Ischaemic Heart Disease. Part I.
      Genesis and objectives].
AB  - In recent years a number of studies concerning ischaemic heart disease prevention
      have been published. Evidence from clinical and epidemiological research has led
      to the formation of new guidelines, especially in the field of secondary
      prevention. Polish Cardiac Society also published recommendations on prevention
      of ischaemic heart disease. Relatively little is known about how well physicians
      in Poland follow the guidelines. No comprehensive studies concerning risk
      factories management after myocardial infarction or myocardial revascularization
      has been conducted in Poland. Patients with established coronary heart disease
      were deemed to be the top priority for prevention. However, little is known about
      quality of medical care in this high risk population. Therefore the Cracovian
      Program for Secondary Prevention of Ischaemic Heart Disease was planned. The aims
      of the Cracovian Program are: to monitor quality of clinical care (both in
      clinical and general practice) in the field of secondary prevention of ischaemic
      heart disease, and to assess factors influencing quality of medical care. The
      secondary aim of the survey is to improve integration of secondary prevention
      into clinical practice through meetings with physicians from Cracow cardiology
      departments and general practitioners, as well as to improve patient compliance
      and motivating them to change their lifestyle. In the first stage, which was
      carried out in 1997-98, an evaluation was conducted to access the realization of
      recommendations concerning secondary prevention. An assessment of integration of
      ischaemic heart disease prevention into clinical practice can now be performed.
      The genesis, aims and methods of the Cracovian Program for Secondary Prevention
      of Ischaemic Heart Disease are discussed in this paper. The quality of hospital,
      as well as postdischarge care in the field of secondary prevention is described
      in the next two publications.

PMID- 11987835
TI  - [Krakow Program for Secondary Prevention of Ischaemic Heart Disease. Part II.
      Secondary prevention of ischaemic heart disease during hospitalization].
AB  - Hospitalization due to ischaemic heart disease provides a possibility to
      introduce patients education, to initiate non-pharmacological treatment and to
      assure patient compliance. The aim the study was to assess the frequency of risk
      factors and the quality of care in the field of secondary prevention in patients
      hospitalized due to acute coronary syndromes or subjected to myocardial
      revascularization. METHODS: The study was carried out in cardiac departments of
      six hospitals serving the area of the city. Consecutive patients (age < or = 70
      years; residing in the Cracow province) were identified according to the
      following clinical diagnoses or procedures: first or recurrent acute myocardial
      infarction, first or recurrent unstable angina, first coronary artery bypass
      grafting or first percutaneous coronary intervention. RESULTS: Data of 536
      patients (140 women and 396 men; mean age--56.6 +/- 8.4 years; hospitalized from
      1.07.1996 to 30.09.1997) were collected from medical records. The rate of blood
      pressure measurement during the first 24-hours of hospitalization was 88.8%.
      Total cholesterol, HDL cholesterol, and triglycerides were assessed in 32.8%,
      30.2%, and 32.3% of patients respectively during the first 24-hours of
      hospitalization. The height and weight were found in 54.9% and 85.1% of medical
      records. Obesity (BMI > or = 30 kg/m2) was found in 20.3% of patients, 36.7%
      smoked, 56.0% had hypertension, 15.5% diabetes and 79.5% had hyper
      cholesterolemia. Medication at discharge was: antiplatelet drugs 86.7%, beta
      blockers 66.4%, ACE inhibitors 50.2% and lipid lowering drugs 27.1%. CONCLUSION:
      There is a need to initiate a comprehensive programme in order to improve quality
      of care in the field of secondary prevention of ischaemic heart disease.

PMID- 11987836
TI  - [Krakow Program for Secondary Prevention of Ischaemic Heart Disease. Part III.
      Secondary prevention of ischaemic heart disease after discharge].
AB  - Even though the majority of actions undertaken within the secondary prevention of
      ischaemic heart disease should be initiated while the patient is still
      hospitalized, the maximum benefit (measured as decreased cardiovascular risk)
      achieved depends mostly on the continuation and modification of these actions in
      the postdischarge period. There is not much known about the quality of medical
      care provided for patients after hospitalization due to ischaemic heart disease.
      The aim of the study was to assess the quality of postdischarge care in the field
      of secondary prevention of ischaemic heart disease. METHODS: Consecutive patients
      (age > or = 70 years; residing in the Cracow province) were identified according
      to the following clinical diagnoses or procedures: acute myocardial infarction,
      unstable angina, CABG and PCI. Out of 536 patients 418 took part in the control
      visit 6-18 months after discharge. Risk factors and medication used were
      assessed. RESULTS: High total cholesterol (> or = 5.2 mmol/l) was found in 65.8%
      of patients, high blood pressure (> or = 140/90 mmHg) in 46.2%, obesity (BMI > or
      = 30 kg/m2) in 24.6%, fasting glucose over 6.0 mmol/l in 17.7% and smoking in
      16.3%. The frequency of antiplatelet drugs and beta-blockers use decreased
      whereas that of lipid-lowering drugs increased in the postdischarge period. The
      highest frequency of use of antiplatelets and lipid-lowering drugs, as well as
      the best control of hypercholesterolemia was found in the PCI group, whereas the
      lowest frequency of smoking was found in the CABG group. CONCLUSIONS:
      Insufficient control of risk factors and the frequency of secondary prevention
      using drugs was found. There is a need to intensify secondary prevention in
      patients with ischaemic heart disease in the postdischarge period.

PMID- 11987837
TI  - [Changes in dietary habits and selected cardiovascular risk factors of the Warsaw
      population over the 5-year observation period (1993-97/98)].
AB  - The aim of the study was to characterise changes in dietary habits and
      cardiovascular risk factors of the Warsaw cohort population over a 5-year
      observation period. Two Warsaw population samples (249 men and 259 women), aged
      35-64, were surveyed in 1993 and resurveyed in years 1997/98. Over a five-year
      observation period, daily dietary cholesterol decreased from 363 mg to 319 mg in
      men and from 263 mg to 232 mg in women, the percentage of energy from fat
      decreased from 38.8% to 34.7% in men and from 37.1% to 31.2% in women, the
      percentage of energy from saturated fatty acids from 13.6% to 11.7% and from
      12.9% to 10.5% respectively. These changes resulted in a significant reduction in
      atherogenicity of the average diet as expressed by Keys score. Intakes of
      vitamins B1 and B2, calcium, magnesium and iron was consistently below
      Recommended Dietary Allowances (RDA) for the Polish population. Participants of
      both genders consumed significantly greater amounts of total bread (35%), milk
      (50%) and butcher meat products (22%). In the same time increase of HDL
      cholesterol level (average of 2.0 mg/dl in men and 3.1 mg/dl in women) and
      decrease of LDL-cholesterol by 5 mg/dl in men was noted.

PMID- 11987838
TI  - [Drug allergy among patients suffering from nasal polyps].
AB  - The study was performed in order to evaluate quantity and morphology of nasal
      polyps in patients with diagnosed drug allergy to aspirin, antibiotics, polocain,
      procain and other drugs. The study included 60 patients (27 females, 33 males
      aged between 18-69 years). Nasal polyp morphology was examined under electron
      microscope and light microscope. Morphological evaluation of epithelial and
      subepithelial structures was done under light microscope, taking not of
      inflammatory infiltration type, basal membrane, as well as degree of intestinal
      edema. Evaluation of epithelial cell type, their relative proportion, as well as
      area percentage covered by cilium, microvilli and squamous epithelium was done
      under electron microscope. Polyps in patients with idiosyncrasy to polish aspirin
      and sodium metamizole (12 patients) featured increased eosinophilic infiltration,
      thickened basal membrane, with elevated eosinophil percentage differential count.
      The epithelial percentage area was covered by squamous cells without villi.
      Polyps associated with idiosyncrasy to polish aspirin differed morphology
      compared to polyps originality from patients allergic to other medications. On
      the other hand polyps from patients allergic to other drugs, such as: penicillin,
      procainamide were morphologically (electron light microscope, light microscope)
      similar to those polyps caused by inflammatory factors.

PMID- 11987839
TI  - [Bone metabolism as assessed with selected markers of bone turnover as well as
      densitometry analysis in patients after successful kidney transplantation].
AB  - The degree of advancement as well as symptoms of renal osteodystrophy improve
      significantly in patients after successful kidney transplantation; however bone
      pathology is still present even after many post-transplant years. The aim of this
      study was to analyze the bone densitometry in patients during different periods
      after kidney transplantation and to assess bone metabolism using selected
      biochemical markers of bone turnover in comparison to healthy controls. Study
      population consisted of 73 patients of mean age 41.7 +/- 12.6 years (27F, 46M)
      mean 34 +/- 42 months after kidney transplantation. Mean period of maintenance
      dialysis prior to surgery was 28.6 +/- 20.3 months. We also analyzed age- and sex
      matched control group of 24 subjects. Three-point densitometry was performed with
      DEXA technique. Serum levels/activity of osteocalcin, C-terminal propeptide of
      procollagen type I (PCTP), alkaline phosphatase (AP) and its bone-specific
      isoform (BAP) as well as desoxypiridine (DPD) urine level were analyzed as
      markers of bone turnover. Serum levels/activity of all mentioned parameters were
      significantly increased (p < 0.001) and urine DPD--significantly decreased (p <
      0.05) in patients as compared to controls. Based on DEXA technique 26% of
      patients were categorized as having osteoporosis, 32.9%--osteopenia and 41.1% as
      normal in bone densitometry. Patients with diagnosed osteoporosis spent
      significantly longer time with functioning graft as compared to those with normal
      densitometry. In addition, subjects with osteoporosis were characterized by
      significantly higher serum level of osteocalcin as compared to those with
      osteopenia and normal DEXA (42.5 +/- 19.9 vs 26.6 +/- 15 ng/ml and 42.5 +/- 19.9
      vs 30.2 +/- 104 ng/ml, respectively; p < 0.05). Identical relationship was also
      observed for serum PTH (128 +/- 42 vs 77.2 +/- 30.4 pg/ml and 128 +/- 42 vs 81.2
      +/- 232 pg/ml, respectively; p < 0.001). There was also significant difference in
      PCTP level in all analyzed groups (203 +/- 85, 171 +/- 69 and 137 +/- 40 ng/ml in
      subjects with osteoporosis, osteopenia and normal; p < 0.05 for all differences).
      BAP activity reduction was observed only in the latter group of patients. Results
      of our study led us to conclude that the prevalence of osteoporosis and
      osteopenia in three-point densitometry among patients with functioning graft is
      high. Increased serum levels/activity of osteocalcin, PCTP, AP and BAP with
      concomitant decrease of urine DPD elimination suggest the predominance of bone
      formation over the bone resorption process.

PMID- 11987840
TI  - [Temporary vascular access in dialysed patients].
AB  - Presently, large venous vessel cannulation is the only procedure for attaining
      immediate dialysis access. As another option, vascular access may be a method for
      guaranteeing drug administration or parenteral feeding. The aim of the following
      paper was to evaluate the course of central venous catheter implantation and
      associated complications. The study included 235 patients (120 male, 115 female)
      between the ages of 24 and 87 years, treated at the Nephrology Department of the
      Jagiellonian University in Cracow from January, 1997 to March, 2001. Choice of
      cannulation location was as follows: subclavian vein--113 cases; internal jugular
      vein--107 cases; femoral vein--15 cases. In 223 patients, implanted catheters
      determined temporary access for hemo-dialysis or other extracorporeal
      circulation, where in 12 cases they determined location for drug administration.
      The following complications were observed during cannulation: accidental artery
      puncture--20 cases; inability to implant cannulation probe and puncture location
      change--16; inability to localize vessel at the first attempt of puncture--12;
      hematoma at puncture location--8; cephalad probe misplacement--6; bleeding at
      puncture site--5; catheter occlusion--25; inflammation at catheter exit site--14;
      catheter bending--10; vessel wall adherence of catheter arterial lumen--8;
      catheter removal by patient--8; damage of Luer ending--5; bacteremia confirmed by
      bacterial culture--4 (including 2 cases of sepsis); subcutaneous emphysema--1
      case. CONCLUSION: Cannulation of large venous vessels is a safe method,
      associated with a small number of complications (23%), where the majority are of
      mild character (85%). In our material, infectious complications comprised only a
      low percentage (7.6%) presenting with an asymptomatic or mild course.

PMID- 11987841
TI  - [Diagnostic progress in spinal muscular atrophy].
AB  - Progress of diagnostic methods in recognition of spinal muscular atrophy (SMA),
      the most common degenerative disease of the nervous system in children has been
      observed in the last years. It has been proved, that all types of SMA,
      phenotypically variable Werdnig-Hoffman and Kugelberg-Welander diseases are
      results of homozygous absence of the telomeric copy of SMN gene located on the
      long arm of chromosome 5; this discovery was very important for mechanisms
      investigation. Based on the evolution of SMA diagnostic, the results of
      diagnostic in 18 children hospitalized in the Department of Pediatric Neurology
      Collegium Medicum of Jagiellonian University are presented. In the years 1995
      1997 the basic procedure for confirming the diagnosis of SMA has been muscle
      biopsy. Molecular studies introduced in 1998 were a chance for confirmation not
      only classical, but other than three main clinical SMA phenotypes. The molecular
      analysis performed in children allowed to confirm diagnosis in 7 patients,
      showing in 5 cases absence of exon 7 of the SMN gene and in 2 children detecting
      deletions involving SMN and NAIP genes. In the less typical cases the results of
      molecular analysis were less definite.

PMID- 11987842
TI  - [Histopathological investigation of the transjugular intrahepatic portocaval
      shunt (TIPS)].
AB  - The aim of the study was to investigate the histological structure of the
      artificial channel connecting one of the portal vein branches with the hepatic
      vein, as an effect of the transjugular intrahepatic portosystemic shunt (TIPS).
      The livers of six patients were investigated. In 4 of them recurrent variceal
      bleedings were an indication for TIPS, in the remaining 2 patients--intractable
      ascites. In all cases portal hypertension was due to liver cirrhosis. All
      patients were estimated as Child-Pugh group C. The period from the stent
      implantation to the moment of investigation ranged from 1 to 7 months. 2 livers
      were removed at the time of liver transplantation, 4 were procured at the
      autopsy. All shunts were patent and in none of the 6 cases dislocation of the
      stent occurred. The wall of the intrahepatic shunts was lined by a granulation
      tissue (pseudointima) covered with a layer of endothelial cells. No thrombosis,
      mechanical damage of the stent or extensive hypertrophy of pseudointima were
      found.

PMID- 11987843
TI  - [Veno-occlusive disease--an important complication in hematopoietic cells
      transplantation].
AB  - Hemopoietic stem cell transplantation is frequently used in clinical practice.
      However, many severe complications limit its usage. One of the most important is
      veno-occlusive disease of the liver (VOD). The key pathophysiologic event is a
      damage to epithelium during chemotherapy. Gradual development of intrahepatic
      portal hypertension leads to clinical manifestations (jaundice, liver
      enlargement, ascites). Many risk factors has been identified (pre-transplant
      liver disturbance, chemotherapy and conditioning, drugs). The diagnosis is based
      on clinical criteria and exclusion of other diseases. Laboratory, haemodynamic,
      ultrasound studies and histopathology are very important in diagnosis. In
      pharmacological prophylaxis heparin is widely used. Therapy requires strict fluid
      and electrolyte balance. Some patients can benefit from transjugular intrahepatic
      portosystemic shunt (TIPS) or liver transplantation. Defibrotide gives more hope
      for patients but further investigations are needed.

PMID- 11987844
TI  - Smack down.

PMID- 11987845
TI  - Taking a stand for Michigan's nurses.

PMID- 11987846
TI  - Conference raises awareness of medication errors and prevention.

PMID- 11987847
TI  - A hug for "Mrs. Gruff".

PMID- 11987848
TI  - Michigan Nurse CareerLink development underway.

PMID- 11987849
TI  - Remember the Michigan Board of Nursing resolution?

PMID- 11987850
TI  - Colleagues in Caring: Michigan's opportunity.

PMID- 11987851
TI  - Testimony before the House Subcommittee on Appropriate Supply and Utilization of
      Michigan's Health Care Workforce of the Standing Committee on Health Policy.

PMID- 11987852
TI  - Campaign practices and information for elections.

PMID- 11987853
TI  - Actions proposed for the 2001 MNA house of delegates.

PMID- 11987854
TI  - Survey indicates sharp increase in usage of NANDA, NOC, and NIC.

PMID- 11987855
TI  - Medicare reimbursement: a hot topic for nurse practitioners.

PMID- 11987856
TI  - Key influences on youth drug use identified.

PMID- 11987857
TI  - Crisis response plan. "When in danger or in doubt, run in circles, scream and
      shout.".

PMID- 11987859
TI  - New tools for health care providers and the public to combat overweight and
      obesity.

PMID- 11987858
TI  - School nurses identify strategies for overweight and obesity control among
      students and staff.

PMID- 11987860
TI  - McComb school nurses--some of the rest of the story....

PMID- 11987861
TI  - Organizations launch nationwide effort to teach emergency lifesaving skills to
      children in the school setting.

PMID- 11987862
TI  - Free information about Marfan syndrome available to school nurses.

PMID- 11987863
TI  - Health illiteracy.

PMID- 11987864
TI  - Focus on mass screening programs: are they effective?

PMID- 11987865
TI  - Show us the money: states not living up to promises on use of tobacco money.

PMID- 11987866
TI  - What would you do?

PMID- 11987867
TI  - Promoting children's mental health. Know the facts.

PMID- 11987868
TI  - After the shooting stops... new facts and resources from top experts on teen
      violence issues.

PMID- 11987869
TI  - Inhalants most popular drug for 12-year-olds.

PMID- 11987870
TI  - Latent inhibition and contextual associations.
AB  - Attenuated responding to a conditioned stimulus (CS) after preexposure to that CS
      (latent inhibition) has traditionally been attributed to reductions in CS
      associability. Alternatively, CS-context associations formed during CS
      preexposure later interfere with the acquisition or expression of CS-outcome
      associations. Three lick suppression experiments with rats contrasted these
      accounts. Presumably, exposure to the context attenuates the CS-context
      association without altering CS associability. With a fixed amount of CS
      preexposure, latent inhibition decreased with increasing context exposure during
      or after (but not before) CS preexposure. When the ratio of context preexposure
      duration to CS preexposure was fixed, latent inhibition increased with CS
      preexposure. These results suggest that latent inhibition is a direct function of
      the strength of CS-context associations formed during preexposure.

PMID- 11987871
TI  - Pigeons presented with sequences of light flashes use behavior to count but not
      to time.
AB  - On randomly ordered trials, pigeons were presented with either a blue or a white
      key that flashed red for 200 ms at a fast (2 flashes/s), medium (1 flash/s), or
      slow (0.5 flashes/s) rate. The blue key signaled a fixed-interval (FI) schedule
      in which the first response after 20 s was reinforced, and the white key signaled
      a fixed-number (FN) schedule in which the first response after 20 flashes was
      reinforced. In Experiments 1 and 2, pigeons showed depressed responding to the
      flash on FI-cued trials and accelerated responding to the flash on FN-cued
      trials. When the response key was periodically blacked out in Experiments 3 and
      4, counting but not timing was eliminated.

PMID- 11987872
TI  - Dissipation of retroactive interference in human infants.
AB  - In 3 experiments with 85 human 3-month-olds, the authors asked whether
      retroactive interference with their memory of the original training stimulus is
      temporary or permanent. Infants learned to move a mobile by kicking and then were
      exposed to a different mobile (Experiment 1) or context (Experiment 2)
      immediately or 3 days afterward (Experiment 3). They were tested after increasing
      delays with the original stimulus, the exposed stimulus, or a completely novel
      stimulus. Retroactive interference was temporary and unrelated to the exposure
      delay. The data are consistent with a retrieval-based account of interference.
      Memory updating (i.e., responding to the interfering stimulus) was coincident
      with retroactive interference, suggesting that retroactive interference is an
      adaptive mechanism that facilitates memory updating within a narrow time window.

PMID- 11987873
TI  - Effect of following an excitatory-inhibitory compound with an intermediate
      reinforcer.
AB  - Pavlovian-conditioned inhibition training of the form A++, AB- (where ++ is a
      strong reinforcer and - is nonreinforcement) was conducted in 3 experiments with
      rats and 1 with pigeons. Then AB+ training was given (in which + is an effective
      reinforcer that is weaker than ++). The + reinforcer was achieved by reducing the
      frequency, lessening the amount, or lengthening the delay with which ++ was
      delivered. All 4 experiments found the AB+ treatment to enhance responding to
      both the excitatory A and the inhibitory B in comparison with untreated control
      stimuli. However, when appropriate assessments were made, the increase was more
      substantial for the inhibitory B. This pattern of results presents challenges for
      most current theories of associative learning.

PMID- 11987874
TI  - Summation in autoshaping is affected by the similarity of the visual stimuli to
      the stimulation they replace.
AB  - Pigeons received autoshaping with 2 stimuli, A and B, presented in adjacent
      regions on a television screen. Conditioning with each stimulus was therefore
      accompanied by stimulation that was displaced from the screen whenever the other
      stimulus was presented. Test trials with AB revealed stronger responding if this
      displaced stimulation was similar to, rather than different from, A and B. For a
      further experiment the training just described included trials with A and B
      accompanied by an additional, similar, stimulus. Responding during test trials
      with AB was stronger if the additional trials signaled the presence rather than
      the absence of food. The results are explained with a configural theory of
      conditioning.

PMID- 11987875
TI  - Perceptual learning with a sodium depletion procedure.
AB  - Rats in a state of salt need prefer a flavor that has previously been paired with
      saline (Experiment 1). In Experiments 2 and 3, rats exposed to 2 saline
      concentrations, presented either concurrently or on separate trials, and each
      paired with a different flavor, showed a preference for the flavor that had been
      associated with the stronger saline. This effect was substantial, however, only
      in those rats that had experienced the concurrent exposure schedule. This effect
      cannot be attributed to a difference in the strength of within-compound
      associations produced by the 2 preexposure schedules (Experiment 4). It is
      suggested that concurrent preexposure can engage a learning process that enhances
      the discriminability of the preexposed stimuli.

PMID- 11987876
TI  - Traveling in time: a time-left analogue for humans.
AB  - Two experiments studied normal humans in an analogue of the time-left procedure
      of J. Gibbon and R. M. Church (1981). In Experiment 1 the "standard" alternative
      (S) was always half the length of the "comparison" time-left link (C), and S
      ranged from 4 to 8 s. Humans showed an increasing preference for the time-left
      alternative with increasing elapsed time in the interval, and indifference points
      strongly supported the idea of a linear, rather than a logarithmic, time scale.
      Experiment 2 used some conditions in which S was greater or less than C/2, and
      preference for the time-left alternative varied systematically with the S/C
      ratio. Data from both experiments showed reasonable superposition, suggesting
      underlying scalar timing processes in time left in humans.

PMID- 11987877
TI  - Cue learning by rufous hummingbirds (Selasphorus rufus).
AB  - The authors investigated the use by wild-living rufous hummingbirds (Selasphorus
      rufus) of flower color pattern and flower position for remembering rewarded
      flowers. Birds were presented with arrays of artificial flowers, a proportion of
      which was rewarded. Once the locations were learned by the birds, the array was
      moved 2 m, and flower color pattern and/or rewarded positions were manipulated.
      The birds' ability to learn which were the rewarded flowers in this 2nd array was
      much more strongly affected by whether the rewarded flowers occupied the same
      positions as in the 1st array than by their color patterns.

PMID- 11987878
TI  - Exercise in pregnancy.
AB  - This article is a brief overview of a vast area of interest, in which we are
      learning that women can be encouraged to help their bodies cope with the
      physiological adaptations of pregnancy, and to enjoy what is usually a very
      special time in their lives. Although the studies carried out have only been very
      small, moderate exercise has not shown any harmful effects in healthy pregnant
      women, and these findings encourage us, as healthcare professionals, to support
      women in their choice to exercise during pregnancy, with known beneficial
      outcomes for both mother and baby.

PMID- 11987879
TI  - Aromatherapy. Introduction into a maternity service.

PMID- 11987880
TI  - Let us pray.

PMID- 11987881
TI  - Traditional midwives. Roots of complementary therapies?

PMID- 11987882
TI  - Promoting successful preterm breastfeeding. Part 1.

PMID- 11987883
TI  - 'Vienna'. A three-dimensional experience.

PMID- 11987885
TI  - The words we use.

PMID- 11987884
TI  - The road from Rome.

PMID- 11987886
TI  - Expand your circle of influence. Part 1.

PMID- 11987887
TI  - Administration of medicines. Midwifery basics.
AB  - Midwifery Basics is a series of articles that cover the main clinical skills
      underpinning midwifery practice. The series uses National Occupational Standards
      (Care Sector Consortium 1998) as a framework to identify the areas of competence
      that students need to achieve in order to master clinical skills. This format is
      combined with the use of 'triggers' to prompt the student to identify what she
      needs to know in order to care for a client in such a situation. The information
      that follows then enables the student to fill in the gaps in her knowledge.

PMID- 11987888
TI  - Midwifery in Tokyo.

PMID- 11987889
TI  - Parent education. Meeting the needs of fathers.

PMID- 11987890
TI  - Complementary therapies in the midwifery curriculum. 2: Development and
      evaluation of a CT module.

PMID- 11987891
TI  - Protecting the public through professional standards.

PMID- 11987892
TI  - A tale of two births.

PMID- 11987893
TI  - Sexually transmitted infections rocket.

PMID- 11987894
TI  - Regulation of puberty.
AB  - Pubertal development is the last phase of a continuum of changing gonadotrophin
      releasing hormone (GnRH) activities. Whether or not puberty tends to start at a
      younger age, as has been recently described in a population of black Americans,
      remains under debate. Such early onset has not been confirmed in different
      European countries. Ideas about the underlying mechanisms responsible for the
      reawakening of GnRH release at the onset of puberty have changed significantly
      during the last decades. At this moment, the common opinion is that neuronal
      outgrowth of both GnRH and other regulatory neurons results in changing
      interactions and activities. Sex steroids, as well as various central
      neurotransmitters, play a role in modulating GnRH release. Active release after
      birth is followed by the restraint of childhood. A re-onset of GnRH excitatory
      activities heralds the onset of puberty. This chapter gives an overview of the
      many factors involved.

PMID- 11987895
TI  - Oestrogens and puberty.
AB  - Oestrogens induce the development of female reproductive tissues. Endogenous
      human oestrogens include oestradiol, oestrone and oestriol. Oestrogen signalling
      in target tissues is dependent on the tissue concentration of oestrogen and the
      interaction of oestrogen receptors with an array of cell-specific co-regulator
      proteins. The diverse mechanisms of oestrogen signalling are complex and
      incompletely understood. In puberty, oestrogen is derived from both gonadal and
      peripheral sources. Originally, oestrogen was only thought to drive feminization
      in females; now, oestrogen is known to be important for pubertal development of
      males as well. Oestrogen is required for normal maturation of the neuroendocrine
      gonadal axis and bone in both sexes, and a variety of other tissues are also
      responsive to oestrogen. Abnormal puberty can be associated with either excessive
      or inadequate oestrogen production. Girls deficient in oestrogen should receive
      replacement in physiological doses. Aromatase inhibitors and anti-oestrogens may
      prove to be useful therapeutic tools in some types of abnormal puberty.

PMID- 11987896
TI  - Androgens and puberty.
AB  - Puberty is associated with an increasing production of androgenic steroids.
      Adrenal androgen formation, termed adrenarche, may precede gonadal testosterone
      synthesis. Both adrenal and gonadal androgens exert their biological effects via
      the androgen receptor, a nuclear transcription factor modulating a specific
      transcription regulation of largely unknown genes. During puberty, virilizing
      actions such as genital enlargement and sexual hair growth can be distinguished
      from anabolic action such as the gain in muscle strength and general changes in
      body composition. Furthermore, androgens play a major role in the initiation and
      maintenance of spermatogenesis. Thus, different androgenic steroids play an
      important role in the process of puberty. The control of their biosynthesis,
      their possible differential action on the molecular level, as well as the
      different target organs in males and females are discussed.

PMID- 11987897
TI  - Inhibins in childhood and puberty.
AB  - Inhibin is a heterodimeric glycoprotein that consists of an alpha-subunit linked
      to either a betaA subunit (inhibin A) or to a betaB subunit (inhibin B) and it
      exists in at least six different isoforms. These isoforms can not be measured
      separately by immunoassays. In boys, serum inhibin B levels change in concert
      with the increase in gonadotrophins. Associated with the postnatal activation of
      gonadotrophin secretion, the early inhibin B secretion is sustained until the age
      of 18-24 months; thereafter serum concentrations subside. In boys, between Tanner
      stages G1 and G2, serum inhibin B concentration again increases, but then
      plateaus. Inhibin A levels in human males are below the detection limit, but in
      girls, during the postnatal activation of gonadotrophin secretion, both serum
      inhibin A and inhibin B concentrations are measurable. Serum inhibin B levels
      correlate positively with age several years before the clinical onset of puberty,
      suggesting increasing follicular activity in late prepuberty. During female
      puberty, the inhibin B level increases from Tanner stage B1 through stage B3,
      suggesting high follicular activity before the development of ovulatory menstrual
      cycles, but serum inhibin A levels become measurable later in puberty, in
      agreement with the idea that inhibin A is mainly produced by the corpus luteum.

PMID- 11987898
TI  - Puberty and bone development.
AB  - Puberty has a key role for bone development. Skeletal mass approximately doubles
      at the end of adolescence. The main determinants of pubertal gain of bone mass
      are the sex steroids, growth hormone and insulin-like growth factors (by their
      effects on bone and muscle mass), 1,25-dihydroxyvitamin D (by stimulating calcium
      absorption and retention) and muscle mass (by regulating modelling/remodelling
      thresholds). Calcium intake is an additional factor influencing bone formation.
      The interactions among these factors are undefined. The accrual of bone mass
      during puberty is a major determinant of peak bone mass and, thereby, of the risk
      of osteoporotic fractures during advanced age.

PMID- 11987899
TI  - Timing of puberty and fetal growth.
AB  - Children born small for gestational age (SGA: birth weight or birth length more
      than 2 standard deviations below the mean score) are at a higher risk of
      perinatal morbidity and mortality and of a number of chronic diseases in later
      life such as hypertension, decreased insulin sensitivity, diabetes mellitus type
      2 and an increased risk of cardiovascular disease. The programming of the
      endocrine axes occurs during critical phases of fetal development and might thus
      be affected by intrauterine growth retardation. Studies in Northern Spanish
      adolescent girls have indicated associations between reduced fetal growth and the
      occurrence of precocious adrenarche, pubarche, hyperandrogenism, polycystic ovary
      syndrome (PCOS) and hyperinsulinism. These findings have attracted much attention
      because it might have serious consequences in later life. However,
      hyperandrogenism and precocious pubarche were not confirmed in a large Dutch
      study in short children born SGA. Two studies reported a lower number of
      follicles in the ovaries in girls born SGA, which might have an impact on
      fertility. Clearly, further studies are required before definite conclusions can
      be drawn. There are still only limited data concerning the timing of puberty in
      children born SGA. Most studies indicate that these children start their puberty
      at a normal age but relatively early within the normal range. Age at menarche
      seems comparable with controls. Data on duration of puberty, influence of puberty
      on attainment of adult height, peak height velocity during puberty and fertility
      are not yet known.

PMID- 11987900
TI  - Delayed puberty in chronic illness.
AB  - Delayed puberty can be defined as the lack of pubertal development at an age of 2
      SD above the mean, which corresponds to an age of approximately 14 years for
      males and 13 years for females, taking both sex and ethnic origin into
      consideration. Its incidence associated with chronic illnesses is unknown;
      however, its clinical importance is relevant due to the larger percentage of
      patients with chronic disorders surviving until the age of puberty. Virtually
      every child with any chronic disease could present with delayed puberty (due to
      recurrent infections, immunodeficiency, gastrointestinal disease, renal
      disturbances, respiratory illnesses, chronic anaemia, endocrine disease, eating
      disorders, exercise and a number of miscellaneous abnormalities). Pubertal delay
      associated with chronic illness is accompanied by a delay in growth and the
      pubertal growth spurt. The degree to which growth and pubertal development are
      affected in chronic illness depends upon the type of disease and individual
      factors, as well as on the age at illness onset, its duration and severity. The
      earlier its onset and the longer and more severe the illness, the greater the
      repercussions on growth and pubertal development. The mechanism that trigger the
      start of physiological puberty remain unknown. Although malnutrition is probably
      the most important mechanism responsible for delayed puberty, emotional
      deprivation, toxic substances, stress and the side effects of chronic therapy,
      among others, have been implicated in the pathophysiology of delayed puberty.
      Therefore, early diagnosis is essential and appropriate and specific therapy
      fundamental.

PMID- 11987901
TI  - Disturbance of pubertal development after cancer treatment.
AB  - Chemotherapy and irradiation to the hypothalamic-pituitary-gonadal axis given for
      childhood cancer carry with them a risk of endocrine late effects. These
      treatment modalities are part of the treatment of common oncological diseases in
      childhood such as acute lymphoblastic leukaemia, brain tumours, Hodgkins lymphoma
      and solid tumours outside the central nervous system. Cranial irradiation of a
      prepubertal child can induce early or even precocious puberty, particularly in
      girls. Hypogonadotrophic hypogonadism may develop at a later stage. Irradiation
      of the gonads, as e.g. part of total body irradiation before bone marrow
      transplantation, will most likely cause gonadal failure and late, incomplete or
      absent puberty in girls. Many boys will experience a normal pubertal development
      except for small testes. Alkylating agents given for a variety of childhood
      cancers, are gonadotoxic. After high doses of these drugs, girls are at great
      risk of developing ovarian failure, whereas boys will usually go through puberty
      normally. Many children receive a combination of several treatment modalities,
      which complicates the prediction of pubertal development. Control and management
      of children with cancer at risk of having a disturbance of puberty is difficult
      and requires detailed knowledge of endocrinology as well as oncology. This
      chapter reviews the common treatments for the most frequent childhood cancers,
      the known effects of the therapy on pubertal development and provides outlines of
      control and management.

PMID- 11987902
TI  - Putative effects of endocrine disrupters on pubertal development in the human.
AB  - Pubertal development is regulated by gonadotrophins and sex hormones. There has
      been a clear secular trend in the timing of puberty during the last century,
      puberty becoming earlier. Although improved nutrition is assumed to be the cause,
      this could partly be associated with exposure to so-called endocrine disrupters.
      Precocious puberty has been described in several case reports of accidental
      exposure to oestrogenic compounds in cosmetic products, food and pharmaceuticals.
      Local epidemics of premature thelarche have also been suggested to be linked to
      endocrine disrupters. Children adopted from developing countries to
      industrialized countries often develop precocious puberty. Not only precocious
      puberty, but also delayed puberty can, theoretically, be associated with exposure
      to endocrine disrupters. While it is very plausible that endocrine disrupters may
      disturb pubertal development, there is very little research on this and,
      therefore, we do not yet have any clear cause-effect relationships in humans.

PMID- 11987903
TI  - The role of mutations affecting gonadotrophin secretion and action in disorders
      of pubertal development.
AB  - A number of mutations that disturb the development and function of the
      hypothalamic-pituitary-gonadal (HPG) axis and cause disturbances in pubertal
      development are known today. These mutations have effects at all levels of the
      HPG axis, from the migration of gonadotrophin releasing hormone (GnRH) neurones
      from the nasal cavity to the hypothalamus, GnRH secretion, GnRH action, pituitary
      gonadotroph differentiation, gonadotrophin synthesis and secretion, right through
      to gonadotrophin action. Most of the mutations are inactivating, thus causing
      hypogonadism and arrest or delay of pubertal development. One exception is the
      activating mutations of the LH receptor, which causes the male-limited
      gonadotrophin-independent precocious puberty. The human mutations and animal
      models with disrupted function of orthologous genes have clarified the molecular
      pathogenesis of hypogonadism and disturbances of pubertal development. The
      correct diagnosis of these disorders using molecular biological techniques is now
      possible. This allows the selection of specific treatments and correct
      counselling of the patients and their families.

PMID- 11987904
TI  - Delayed puberty.
AB  - Puberty is the acquisition of secondary sexual characteristics associated with a
      growth spurt and resulting in the attainment of reproductive function. Delayed
      puberty is diagnosed when there is no breast development by 13.4 years of age in
      a girl and no testicular enlargement by 14.0 years in a boy. The aetiologies are:
      (i) pubertal delay, either with constitutional delay of growth and puberty or
      secondary to chronic illness, and (ii) pubertal failure, with hypogonadotrophic
      (defect in the hypothalamo-pituitary region) or hypergonadotrophic (secondary to
      gonadal failure) hypogonadism, or both (secondary to radio/chemotherapy). The
      investigation includes: history, auxological data and pubertal development
      examination. Boys usually require treatment and, if they do not respond,
      investigation. In girls it is appropriate to measure the thyroid function and
      karyotype first and, if necessary, to offer treatment. If they present with
      dysmorphic features, or positive familial history, an assessment is required
      before treatment.

PMID- 11987905
TI  - Early puberty in girls.
AB  - Early puberty is not well defined in paediatric endocrinology. This chapter
      reviews the current insights on definitions, patient groups and treatment
      modalities in girls with early puberty. It is concluded that there is no clear
      evidence for a beneficial effect of gonadotrophin releasing hormone agonist
      (GnRHa) treatment in auxological terms. A clinical approach is presented,
      including both auxological and psychological items. Further research is needed to
      answer the question of whether early puberty should be treated with GnRHa.

PMID- 11987906
TI  - Treatment of central precocious puberty.
AB  - This chapter describes several aspects of the management of treatment in girls
      and boys with central precocious puberty. Although there is some controversy
      about the indication for gonadotrophin releasing hormone (GnRH) agonist treatment
      in the literature, a list of clear indications is presented and monitoring
      requirements for treatment are discussed with reference to the pertinent
      literature. The development of clinical, psychological, hormonal, sonographical
      and auxological parameters that can be expected during GnRH agonist treatment is
      described in detail. In view of the scant evidence-based knowledge, we review the
      final outcome of patients treated with GnRH agonists with respect to
      reversibility of hormonal suppression, reproductive function, final height and
      side effects. The data published so far show that GnRH agonist treatment using
      the modern depot preparations is not only convenient but also safe, with
      relatively minor side effects. The outcome in terms of final height is favourable
      in the majority of patients.

PMID- 11987913
TI  - Advances in the immunological monitoring of childhood acute lymphoblastic
      leukaemia.
AB  - In children with acute lymphoblastic leukaemia (ALL), measurements of minimal
      residual disease (MRD) during therapy provide crucial information about the
      response to treatment and the risk of relapse. Flow cytometry is a practical and
      widely applicable tool for monitoring MRD in patients with ALL. This approach is
      based on the identification of immunophenotypes expressed by leukaemic cells but
      not by normal lympho-haematopoietic cells in bone marrow and peripheral blood.
      These phenotypes can identify one leukaemic cell among 10 000 normal cells and
      are currently applicable to at least 90% of patients with ALL. A strong
      correlation between flow cytometric measurements of MRD during clinical remission
      and treatment outcome has been demonstrated, suggesting that these assays should
      be incorporated into treatment protocols.

PMID- 11987914
TI  - Monitoring minimal residual disease using chromosomal translocations in childhood
      ALL.
AB  - Clonal chromosomal abnormalities have been identified in approximately 80% of
      childhood ALL. In most instances the genes disrupted by these abnormalities have
      been identified, thus providing important insights into disease pathogenesis and
      normal cellular physiology. Polymerase chain reaction (PCR) amplification of
      fusion transcripts resulting from chromosomal translocations has emerged as a
      sensitive and reproducible method to monitor minimal residual disease (MRD) in
      childhood ALL. The measure of the initial response to therapy in patients who
      have achieved complete remission by morphological standards can dissect clinical
      heterogeneity within the genetically homogeneous childhood ALL subgroup.
      Moreover, MRD monitoring can be applied to predict impending relapses early.
      Despite notable progress with this method, several critical issues must be
      resolved before MRD determinations can be routinely considered in clinical
      decision making. This chapter will focus on the main progress and common pitfalls
      in the PCR detection of chromosomal translocations applied to clinical studies.

PMID- 11987915
TI  - Molecular monitoring of residual disease using antigen receptor genes in
      childhood acute lymphoblastic leukaemia.
AB  - Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are assumed to
      be unique 'fingerprint-like' sequences for each acute lymphoblastic leukaemia
      (ALL). Various clonal Ig/TCR gene rearrangements can be identified at diagnosis
      in virtually all childhood ALL patients, representing molecular targets for
      detection of minimal residual disease (MRD) during follow-up analysis. The usage
      of at least two MRD-PCR targets per patient generally ensures high sensitivity
      (</=1:10(4) normal cells) and prevents false-negative results owing to ongoing or
      secondary rearrangements.MRD monitoring in childhood ALL employing Ig/TCR gene
      rearrangements as PCR targets has significant prognostic value. This is
      particularly powerful for evaluation of early treatment response and consequently
      can be used for improved therapy stratification. Prolonged continuous MRD
      monitoring might be important for patients at intermediate or high risk of
      relapse. MRD monitoring in second complete remission identifies patients with
      excellent drug sensitivity and predicts outcome after stem cell transplantation.

PMID- 11987916
TI  - Clinical relevance of MRD in children undergoing allogeneic stem cell
      transplantation for ALL.
AB  - The toxicity and expense of allogeneic stem cell transplantation (ASCT) is such
      that it is currently reserved for the treatment of children deemed to be at
      unacceptable risk of relapse when treated with chemotherapy alone. Although ASCT
      carries at least 10% treatment-related mortality, the commonest cause of death in
      transplant recipients is relapse of the original disease. This chapter reviews
      the literature pertaining to the clinical significance of minimal residual
      disease (MRD) in ASCT. Particular emphasis is placed on the strong correlation
      between pre-transplant minimal residual disease burden and clinical outcome.
      Recommendations for the design of MRD-based therapeutic trials are given.

PMID- 11987917
TI  - Molecular analysis of minimal residual disease in adult acute lymphoblastic
      leukaemia.
AB  - Despite intensive chemotherapy and stem cell transplantation (SCT) programmes,
      overall survival in adult acute lymphoblastic leukaemia (ALL) remains poor
      compared to that in childhood ALL. Despite clinical and morphological remission
      being achieved by over 80% of patients, 5-year survival is limited to 40% of
      patients, clearly indicating that morphology is insufficient in predicting future
      outcome. Molecular assessment of residual disease in bone marrow using
      immunoglobulin genes as markers of clonality has recently been evaluated in a
      large adult ALL study in our institution. Analysis of disease-free survival (DFS)
      rates for minimal residual disease-(MRD-) positive and -negative patients
      established that MRD positivity was associated with increased relapse rates at
      all times, being most significant at 3-5 months post-induction and beyond. Pre
      autologous SCT tests are predictive of outcome, but for allogeneic SCT outcome is
      related to results of the tests after the procedure rather than before. The
      association of MRD test results and DFS was independent of, and greater than,
      other standard predictors of outcome and is therefore important in determining
      treatment for individual patients.

PMID- 11987918
TI  - Molecular measurement of minimal residual disease in Philadelphia-positive acute
      lymphoblastic leukaemia.
AB  - The Philadelphia chromosome (Ph) is found in approximately 5-25% of acute
      lymphoblastic leukaemia (ALL) cases and is the harbinger of a poor outcome.
      Polymerase chain reaction (PCR) assays can detect leukaemia-specific genetic
      lesions down to a sensitivity approaching one leukaemia cell in a background of a
      million normal cells. In Ph(+) ALL, the unique BCR-ABL translocation is thus a
      specific target for the detection of minimal residual disease (MRD). After
      chemotherapy or transplantation the detection of residual BCR-ABL transcripts is
      associated with a high risk of subsequent relapse. With the advent of novel
      therapeutics that target the structure and function of BCR-ABL, the detection of
      MRD may allow for targeted therapy that could abort a potential relapse.

PMID- 11987919
TI  - Immunological evaluation of minimal residual disease (MRD) in acute myeloid
      leukaemia (AML).
AB  - Immunophenotypic analysis of leukaemic cells using multiparametric flow cytometry
      has proved to be an attractive approach for MRD investigation in acute
      lymphoblastic leukaemia (ALL); by contrast, information on acute myeloid
      leukaemia (AML) is still scanty. Here, we first review the methodological
      strategies for these studies. Triple or quadruple antigenic combinations,
      analysed by multiparametric flow cytometry, have shown that in 80% of AML
      patients it is possible to identify aberrant or uncommon phenotypic profiles on
      blast cells, thereby allowing their distinction from normal cells and their use
      as leukaemia-associated phenotypes (LAP). We also focus on technical aspects that
      are important in the definition of LAP. We then review pitfalls that could
      potentially affect results using this approach. Finally, we review available
      information concerning the clinical value of these studies. Although reported
      data in the literature are still scanty, several authors have shown that this
      technique could be used for the prognostic evaluation of AML patients, when
      immunophenotypic evaluation is applied after induction therapy.

PMID- 11987920
TI  - Minimal residual disease in acute myeloid leukaemia.
AB  - Relapse remains the main cause of treatment failure in acute myeloid leukaemia
      (AML). Studies to date suggest that monitoring of minimal residual disease (MRD)
      in AML is useful in identifying patients at high risk of relapse from those in
      durable remission. This chapter describes the methodological advances in the
      detection of MRD and, in particular, focuses on the development of highly
      sensitive RT-PCR techniques, including real-time, for quantifying MRD.
      Preliminary results on the clinical utility of MRD monitoring in AML with t(8;21)
      and inv(16) are promising and provide the basis for further evaluation by
      quantitative real-time analysis in prospective clinical trials. For AML without a
      specific fusion transcript, the WT1 gene is an alternative molecular target. The
      clinical value of quantitative MRD monitoring in AML, however, will need to be
      confirmed in future studies.

PMID- 11987921
TI  - The significance of minimal residual disease in patients with t(15;17).
AB  - Acute promyelocytic leukaemia (APL) is characterized by the t(15;17)(q22;q21)
      leading to the formation of PML-RARalpha and RARalpha-PML fusion genes which
      provide suitable targets for the assessment of minimal residual disease (MRD).
      Studies have focused upon detection of PML-RARalpha because, although assays for
      RARalpha-PML transcripts are more sensitive, they are not applicable to 25% of
      cases. Among patients receiving standard therapy (ATRA and anthracycline-based
      chemotherapy), qualitative assays using a nested reverse transcriptase-polymerase
      chain reaction (RT-PCR), which typically achieve sensitivities of 1 in 10(4),
      have been found to provide independent prognostic information suitable for
      directing an approach to treatment. Detection of PML-RARalpha at the end of
      consolidation, or subsequent recurrence of PCR positivity, heralds relapse, which
      may, however, be averted by additional therapy leading to improvements in
      survival for this "high-risk" subgroup of patients. MRD analysis has also proved
      of value in predicting response to autologous transplant procedures undertaken in
      second complete remission and in directing the need for additional therapy in the
      post-transplantation setting. Overall, these studies undertaken within the
      context of a relatively homogeneous disease entity confirm that MRD monitoring
      provides independent prognostic information, serving as a valuable model for
      improving treatment strategy in other molecularly defined subsets of acute
      myeloid leukaemia (AML). Nevertheless, conventional nested RT-PCR assays fail to
      detect residual disease in a significant proportion of patients who ultimately
      relapse, which may be a reflection of RNA quality and/or assay sensitivity.
      Therefore, it is hoped that "real-time" quantitative RT-PCR technology (RQ-PCR)
      which permits quantification of fusion gene transcripts in relation to endogenous
      control genes will be even more predictive of outcome and achieve greater
      standardization of MRD detection in the context of large-scale clinical trials.

PMID- 11987922
TI  - Minimal residual disease in chronic myeloid leukaemia patients.
AB  - In many ways, chronic myeloid leukaemia (CML) serves as a paradigm for the
      utility of molecular methods in the diagnosis of malignancy or for monitoring the
      response of the patient to therapy. The Philadelphia (Ph) translocation provides
      an elegant example of how cytogenetic findings provided the starting point for
      understanding the genetic mechanisms involved in leukaemogenesis. The degree of
      reduction in tumour load after therapy is an important prognostic factor for CML
      patients. Several approaches have been introduced that can specifically detect
      the Ph translocation or its products; these approaches include fluorescent in
      situ hybridization, Southern blotting, western blotting and reverse transcriptase
      polymerase chain reaction (RT-PCR). Because non-quantitative RT-PCR analysis
      after therapy gives only limited information, quantitative or semiquantitative RT
      PCR assays have been developed that enable the kinetics of residual BCR-ABL
      transcripts to be monitored over time in patients after allogeneic stem cell
      transplantation, interferon-alpha, or STI571 therapy.

PMID- 11987923
TI  - Monitoring disease in lymphoma and CLL patients using molecular techniques.
AB  - Over the past decade considerable advances have been made in the sensitivity of
      detection of residual lymphoma and leukaemia cells. Assays based on the
      polymerase chain reaction (PCR) can detect one tumour cell in up to 10(5) to
      10(6) normal cells. The identification and cloning of breakpoints associated with
      specific chromosomal translocations has made possible the application of these
      techniques to a variety of lymphoid malignancies. In parallel, B cell
      malignancies exhibit rearrangements of their immunoglobulin genes that are also
      suitable targets for PCR amplification to identify residual cells. Although these
      techniques provide a useful adjunct to standard methods of detection and
      diagnosis, their role in determining disease outcome remains investigational.
      There is confusion as to whether it is necessary to eradicate PCR-detectable
      lymphoma cells for cure, so it is not yet possible to determine whether the
      detection of residual lymphoma cells by PCR is an indication to continue therapy.

PMID- 11987924
TI  - Minimal residual disease monitoring in multiple myeloma.
AB  - Traditionally, response to treatment in multiple myeloma has been measured by the
      serum or urinary paraprotein and the percentage of plasma cells in the bone
      marrow. The use of allogeneic and autologous transplantation has increased the
      complete response rate and overall survival in patients with myeloma, and in
      order to assess the effects of such treatments accurately more sensitive methods
      for assessing residual disease have been introduced. The aim of this chapter,
      therefore, is to describe the available techniques to assess response, monitor
      residual disease and predict relapse in myeloma. The traditional techniques of
      paraprotein measurement using electrophoresis and immunofixation are compared
      with more sensitive approaches involving the polymerase chain reaction for
      detecting rearrangements of the immunoglobulin heavy-chain region and flow
      cytometry for detecting malignant plasma cells. Emphasis is placed on the
      advantages and disadvantages of each method and its utility in the clinical
      setting.

PMID- 11987927
TI  - Recent advances in diagnosis and comprehensive management of more general spinal
      disorders.

PMID- 11987928
TI  - How epidemiology contributes to the management of spinal disorders.
AB  - Back pain constitutes a nearly universal experience, Point, one-year period and
      lifetime prevalence reach or exceed, in some European countries, 40%, 70% and
      80%, respectively. No health care system is able to cope with the entire quantity
      and spectrum of cases. Clinically useful distinctions are urgently required. A
      basic classification distinguishes specific from non-specific cases. Non-specific
      back pain may then be graded on its actual severity in terms of pain intensity
      and disability. This already implies limited prognostic information. Staging
      assumes a more or less unidirectional course with definable phases and transition
      periods and definitely adds to prognosis (cf. the TNM-system in oncology). So far
      there seems to be no generally accepted staging system for chronic back pain,
      although some promising proposals can be presented. The disorder, once it has
      become chronic, has a rather unfavourable prognosis, although single episodes
      still have a high probability of completely resolving within a few weeks. An
      underestimated risk factor for a chronic-disabling course of current back pain is
      (besides its acute grade and stage) its previous history.

PMID- 11987929
TI  - The economic burden of low back pain: a review of studies published between 1996
      and 2001.
AB  - Low back pain (LBP) poses an economic burden to society, mainly in terms of the
      large number of work days lost by a small percentage of patients who develop
      chronic LBP. The object of this review is to gain a better understanding of the
      societal costs of LBP and to see whether current clinical management follows
      evidence-based guidelines and is economically attractive, by reviewing studies on
      LBP with economic implications. To this end, the Medline database was searched
      between 1996 and 2001 using appropriate keywords, broadly defined. A total of 372
      abstracts were screened and paper copies of 73 potentially relevant articles were
      obtained. It was found that the cost of LBP illness was high and was comparable
      to other disorders such as headache, heart disease, depression or diabetes, but
      actual cost estimates varied depending on the costing methodology employed. A
      small percentage of patients with chronic LBP accounts for a large fraction of
      the costs. Excessive and inappropriate use of diagnostic or therapeutic services
      can be documented but varied by region and provider type. Management according to
      evidence-based guidelines was not necessarily economically attractive.
      Interventions for acute or chronic LBP failed to show economic benefits, but
      demonstrated modest clinical benefits, which suggested a weak relationship
      between clinical and economic outcomes. The conclusion was that common
      definitions and costing methodologies need to be found to gain a better
      understanding of the true costs to society and to make studies comparable. A
      better definition is needed for the type for patient with LBP for whom
      therapeutic management is most likely to have a long-lasting economic benefit.

PMID- 11987930
TI  - How does neuropathophysiology affect the signs and symptoms of spinal disease?
AB  - A complex relationship exists between back pain and the presence of spinal
      disease. Particularly in chronic situations, back pain and its behavioural and
      emotional consequences are as likely to reflect the influence of psychosocial
      factors as any underlying spinal pathology. Nevertheless, physical factors are
      clearly important and it is significant that whereas in normal discs only the
      outer third of the annulus fibrosus is innervated, a much more extensive
      innervation develops in the presence of degeneration. Inflammation, as evidenced
      by leukocyte infiltration and expression of inflammatory mediators, is associated
      with disc degeneration and serves to alter the neural responses resulting in
      local and referred pain. It is probable that similar inflammatory processes, as
      well as direct root compression, contribute to radicular symptoms following disc
      herniation. An appreciation of these mechanisms encourages the search for novel
      treatments and permits a more rational and effective use of existing strategies
      for relieving pain.

PMID- 11987931
TI  - What is the rational diagnostic approach to spinal disorders?
AB  - A problem that is encountered in patients with low back pain is that a definite
      diagnosis is rare. The heart of our clinical dilemma is how best to diagnose
      those rare patients with severe disease as early as possible. The main reasons
      for diagnostic errors have been summarized in this chapter. Numerous guidelines
      have been developed to help in the approach to this difficult problem. However,
      the limitations of such an approach are highlighted. History and clinical
      examination are the best single test for diagnostic purposes and neither
      questionnaires nor computers can replace the clinician. However, the values of
      clinical abilities should not be overestimated. Finally, the clinical application
      of guidelines needs to be re-evaluated for each individual patient.

PMID- 11987932
TI  - Neuroradiology of spine degenerative diseases.
AB  - Degenerative disease of the spine is one of the most common clinical entities and
      affects the intervertebral discs, including opposing vertebral endplates, the
      intervertebral posterior joints and the ligaments. The most severe primary spinal
      degenerative changes are found in the lower cervical and lumbar spine regions.
      The spine contains three different types of joints, each of which presents its
      own pattern of degenerative disease: (i) cartilaginous joints, represented by the
      intervertebral disc or, more specifically, the functional unit defined as the
      'vertebro-disc connection'; (ii) synovial joints, represented by the posterior
      intervertebral joints, sacro-iliac and costovertebral joints; (iii) fibrous
      joints, mainly found in the principal ligaments such as the posterior
      longitudinal ligament and the yellow ligaments. With regard to radicular pain,
      root compression alone does not fully account for root pain following disc-root
      conflict, but it is, nevertheless, considered to be the main cause of pain. We
      will try to explain that the origin of pain is multi-factorial and that
      inflammation probably predominates over merely mechanical mechanisms. To
      conclude, we will consider whether vertebral arthrosis can be construed as the
      body's decision to favour the spine's static function over its dynamic role when
      joint 'hypermobility' linked to chronic load in old age could cause severe
      structural damage to the bony vertebral structures. This hypothesis should also
      embrace a further concept: ageing of the spine is not merelychronological.
      Themostaccurate interpretation tha tcan account for similar degenerative
      phenomena encountered in the young is that of abnormal static and dynamic loading
      stress.

PMID- 11987933
TI  - Self-care techniques for acute episodes of low back pain.
AB  - Guidelines recommend minimal medical intervention for acute non-specific low back
      pain. However, patients often request strategies to reduce symptoms and recover
      quickly. Self-care techniques that do not contradict current evidence-based
      recommendations may be suggested. Self-care techniques can reduce costs and
      iatrogenic complications that can occur with medical treatment. They may also
      increase the patient's perception of control and improve long-term outcome. A
      shift in paradigm for the health care provider and the patient is required for
      self-care to be successful. These issues, as well as self-care approaches such as
      medication, exercises, modalities and mind-body techniques are discussed.
      Practice points for each approach are given.

PMID- 11987934
TI  - Advances with analgesics and NSAIDs for the treatment of spinal disorders.
AB  - One of the major developments with regard to chronic non-malignant pain in these
      last few years has been a better understanding of the mechanisms that act to
      maintain pain, while inferences about the pathophysiology have facilitated
      therapeutic decision-making. This chapter reviews the strength of evidence for
      the therapeutic effect of pharmacological symptomatic approaches using non
      steroidal anti-inflammatory agents, opioids and co-analgesics in acute and
      chronic back pain with an emphasis on the results of randomized controlled trials
      as well as on the need for long-term comparative trials of drug efficacy,
      toxicity and compliance.

PMID- 11987935
TI  - Update on use of instrumentation in lumbar spine disorders.
AB  - The past 20 years have witnessed significant changes in the indications for and
      use of instrumentation in lumbar spine surgery. Absolute indications for surgical
      instrumentation include cases of clearly defined instability that commonly occur
      in the setting of trauma, tumour and infection. Relative indications for
      instrumentation must consider the clinical context and individual patient
      characteristics but may include cases of spondylolisthesis, junctional stenosis
      and pseudarthrosis. The use of instrumentation in the surgical treatment of
      degenerative disc disease is prevalent but remains highly controversial. Pedicle
      screws and interbody cages represent alternative forms of instrumentation with
      substantial clinical evidence supporting their safety and efficacy when applied
      in the correct clinical settings. Minimally invasive and computer-assisted
      surgical techniques have shown promising early results but must be subject to
      longer-term scrutiny. The development of prosthetic disc replacements is an
      exciting area of research, but clinical results have not approached the success
      currently enjoyed by hip and knee prostheses, and these devices should be
      considered experimental. One of the goals of instrumentation is to enhance the
      rate of spinal fusion. However, achievement of solid radiographic fusion does not
      guarantee a clinically successful outcome and, conversely, excellent results can
      be obtained in the setting of radiographic pseudarthrosis. The most important
      determinant of favourable surgical outcome is appropriate patient selection
      through a sound understanding of surgical indications.

PMID- 11987936
TI  - What are the advances for surgical therapy of inflammatory diseases of the spine?
AB  - Surgery for rheumatoid arthritis (RA) and spondyloarthropathies is a palliative
      surgery, and testifies to the failure of conservative treatment. In RA, surgery
      is generally used to deal with upper cervical instability and peridens pannus
      compression. These complications can have dramatic neurological consequences and
      can even be life threatening. Every effort must be made to avoid unnecessary
      surgery but, if needed, the indication must be precise and timely to be
      efficient. Instrumented fusion is indicated but the need for pannus excision is
      discussed. In ankylosing spondylitis (AS), major deformity will be the indication
      for corrective surgery if this deformity induces a marked decrease in the field
      of vision, thoracicy or abdominal problems or respiratory and mandibular troubles
      in the cervical spine. Different types of osteotomies with instrumented fixation
      are described. In AS. surgery is also indicated in fractures that are potentially
      unstable. At the cervical level these fractures are a surgical emergency.
      Neurological compressions and spondylodiscitis are other reasons for surgery in
      AS. Complications of other spondyloarthropathies, which include accompanying
      psoriasis, reactive arthritis, enteropathic arthritis or Behcet's syndrome are
      occasionally treated surgically along the same lines as RA or AS. Surgery for
      spinal inflammatory disorders involves major procedures with a high rate of
      severe complications. The indications for this type of surgery must be extremely
      precise and both the surgeon's and the patient's expectations must be clear and
      realistic. The surgery should only be performed by a surgeon who is experienced
      with this type of patient and procedure but, furthermore, it should also only be
      camed out in a centre with a team of neurologists, anaesthetists, nurses and
      physical therapists who have the expertise to work with these pathologies and
      these often severely debilitated patients. Only under these conditions will the
      outcome justify the burden and the risks.

PMID- 11987937
TI  - Does neural blockade and other neurosurgical modalities offer a durable pain
      relief for spinal disorders?
AB  - Various minimally invasive techniques have been performed to fight pain
      originating at bony and soft tissue spine elements. Of these, denervation of the
      nerve supply to the facet joints is the only technique for which three
      multidisciplinary clinical studies have been conducted, according to state-of-the
      art study criteria, to produce evidence-based efficacy data. Of all of the
      morphopathological factors contributing to chronic spinal pain, facet joints play
      a major role in generating spinal pain due to hypermobility or joint
      degeneration. This is commonly referred to as facet joint syndrome (FJS). Other
      important non-morphological co-morbidity factors (mostly psychiatric, social or
      occupational in origin) also play an important role in mediating spinal pain.
      From the existing evidence-based data, there seems to be no durable pain relief
      in FJS using standard lesioning techniques (thermal and/or cryo). Efficacy
      compared to placebo lasts for only 4 weeks. Only those patients with spinal canal
      stenosis and concomitant chronic FJS appear to benefit after microsurgical
      decompression of the narrowed spinal canal. However, the database for this claim
      is low since low back pain is not the major focus in the clinical symptoms
      reported by the patients.

PMID- 11987939
TI  - Psychosocial benefits of sentinel lymph node biopsy in the management of
      cutaneous malignant melanoma.
AB  - Lymphoscintigraphy combined with sentinel lymph node biopsy has become a powerful
      and sensitive tool in establishing nodal spread in cutaneous melanoma, as well as
      in breast and other cancers. Although the technique is reliable and validated,
      there is, as yet, no proven clinical benefit. A suggested benefit of sentinel
      lymph node biopsy is that a negative biopsy may decrease the psychological
      morbidity associated with malignancy by reassuring the patient that he or she has
      localised disease. We studied a group of patients with cutaneous melanoma who
      underwent sentinel lymph node biopsy, and found that although they did gain some
      psychosocial benefit from the procedure, this was short term and they were still
      significantly concerned about their disease status.

PMID- 11987940
TI  - The outcome of oral mucosal grafts to the orbit: a three-and-a-half-year study.
AB  - A 3 1/2 year audit of the outcome of oral mucosal grafts was conducted at the
      occuloplastic service of Wentworth Hospital, Durban, South Africa. We studied 17
      consecutive patients with ages ranging from 2 years to 83 years; young males
      predominated. The causative pathologies included six gunshot wounds, three
      retinoblastomas, two congenital abnormalities, two childhood traumas, a chemical
      burn, an occular pemphigoid, a stab wound and a firework injury. We treated 14
      patients for a contracted socket, and performed mucosal grafts to the globe in
      the other three. Prostheses were successfully fitted in 12 of the patients with a
      contracted socket and in one patient with microphthalmia. Of the former patients,
      10 had a good result and two had a fair result. Out of the 14 patients with a
      contracted socket, 10 required a repeat procedure. An onlay prosthesis was used
      instead of an inlay prosthesis in one patient because of the child's social
      circumstances; one patient was lost to follow-up. During the first year of the
      study, a thermoplastic conformer of Stent's composition was used. This was later
      changed to a plug of medicated paraffin gauze, which was easier to use. A
      permanent prosthesis was fitted 1 week postoperatively. The crucial factor for
      success was that there should be no delay between removing the plug and inserting
      the prosthesis. A single-stage reconstruction of the orbital wall and socket
      using costal cartilage and temporalis fascia together with an oral mucosal graft
      is discussed for reconstruction following gunshot wounds or retinoblastoma
      enucleation and radiotherapy. Oral mucosal grafts can be used successfully to
      reconstruct the conjunctiva on the globe and in the fornices.

PMID- 11987941
TI  - Clinical experience with non-penetrating vascular clips in free-flap
      reconstructions.
AB  - To date, the gold standard for performing a microvascular anastomosis has been
      the penetrating suture with attached needle. During the last two decades, non
      penetrating techniques have been introduced, including the Unilink system for end
      to-end anastomoses, and the VCS clip-applier system for both end-to-end and end
      to-side anastomoses. The aim of this study was to compare the results of
      different techniques used to create microvascular anastomoses in free-flap
      reconstructions. Between January 1995 and October 1999, we performed 474
      microvascular anastomoses in 216 consecutive free-tissue transfers. The
      anastomosis techniques included manual sutures (42%), Unilink rings (34%) and VCS
      clips (24%). Seven combined sutured-clipped anastomoses were excluded from
      further analysis. The mean anastomotic time when rings were applied was
      significantly shorter than when using clips (P 0.0001) or sutures (P 0.0001).
      Venous anastomoses using clips took less time than those using sutures (P 0.05).
      There were 19 anastomotic failures, all of which lead to early flap failure. Ten
      flaps were salvaged by early reoperation; nine flaps were lost. Three more flaps
      were lost as a result of other causes, bringing the flap survival rate down to
      94.4%. Early flap failure was caused by failure of the arterial anastomosis in
      eight cases; all of them were sutured (these represented 5% of all arterial
      anastomoses with sutures). None of the clipped arterial anastomoses failed. Early
      flap failure was caused by failure of the venous anastomosis in 11 patients.
      Three of these anastomoses were sutured (representing 6% of all venous
      anastomoses with sutures), seven were anastomosed with rings (representing 5% of
      all venous anastomoses with rings) and one was clipped (representing 2% of all
      venous anastomoses with clips). Both the VCS clip-applier system and the Unilink
      system are easy to handle and allow fast microvascular anastomoses without
      intraluminal penetration. The patency rate of clipped vessels is at least as good
      as the patency rates of vessels anastomosed using sutures or rings.

PMID- 11987942
TI  - Immediate versus delayed free TRAM breast reconstruction: an analysis of
      perioperative factors and complications.
AB  - Immediate breast reconstruction provides superior psychological benefit to the
      patient compared with delayed reconstruction, and has a financial advantage.
      Smokers undergoing immediate free TRAM breast reconstruction have a higher
      incidence of flap necrosis than smokers undergoing delayed free TRAM
      reconstruction. Whereas the differences in psychological benefit, effects of
      smoking and cost are well addressed in the literature, the differences in
      morbidity between immediate and delayed free TRAM breast reconstruction are still
      unknown. Knowledge of any differences would help to determine the best timing for
      reconstruction, and would support surgical decision making and preoperative
      patient advice. We present a retrospective review of 105 consecutive free TRAM
      breast reconstructions performed in 97 patients (89 unilateral and eight
      bilateral reconstructions). There were 48 immediate reconstructions and 57
      delayed reconstructions. In the immediate-reconstruction group six flaps required
      revision of the anastomosis, and three flaps (6%) were lost. In the delayed
      reconstruction group five flaps required revision of the anastomosis, and only
      one flap (2%) could not be salvaged. Delayed healing of the chest-wall skin flaps
      only occurred in immediate reconstructions (16%, P = 0.017).

PMID- 11987943
TI  - Experience of explantation of Trilucent breast implants.
AB  - On 6 June 2000, the Medical Devices Agency (MDA) recommended that all Trilucent
      (soya-bean-oil filled) breast implants should be removed. This accelerated a
      trend that had already begun in our unit. This study follows our previous report
      on a 3 year series of women with Trilucent breast implants. The aim was to
      present our operative findings at explantation, and to correlate them with the
      preoperative signs and symptoms, the postoperative complications and the details
      of the hospital stay. In total, 44 patients (82 implants) underwent explantation,
      of whom 34 were cosmetic cases and 10 were reconstructive. Five patients had
      their implants removed before the MDA announcement. Implant rippling was the most
      common problem reported (25%), followed by pain (18%), implant deflation (9.1%)
      and capsular contracture (4.5%). Free oil was seen around the implant in 15
      cases; four of these presented with clinical deflation, and three with rippling.
      The remaining eight patients were asymptomatic. We conclude that these implants
      tend to bleed, as evidenced by the presence of free oil around the implant in 34%
      of patients. The absence of free oil in 73% of the patients who presented with
      rippling suggests that the leaking oil is often metabolised and absorbed. The
      findings of this study are significant for women in whom free oil was found
      around the implant during explantation, and for those who still have Trilucent
      implants in place, for whatever reason, in spite of the MDA recommendation.

PMID- 11987944
TI  - Mammary implants: laboratory simulation of recreational diving conditions.
AB  - To ascertain whether mammary implants are prone to changes in conformation or
      structure if they are submitted to recreational dives, eight mammary implants
      were submitted to 40 simulated dives to imitate an average recreational diving
      schedule. Matching implants were used as a control group. Photographs were taken
      before and after completion of the protocol. All implants were observed for
      changes in volume and checked for integrity. Variations in density were evaluated
      using a Tc scan. No changes in volume occurred after each dive. None of the
      implants showed ruptures, and Tc scanning failed to reveal any differences in
      density between tested and control implants. Cohesive-gel implants submitted to
      the simulated dives showed some morphological alterations. This study indicates
      that the mammary implants tested could be implanted in a sports diver, but raises
      concern about whether the increased exposure to stress could negatively affect
      their durability.

PMID- 11987945
TI  - Perforator-based fasciocutaneous island flaps for the reconstruction of axillary
      defects following excision of hidradenitis suppurativa.
AB  - Hidradenitis suppurativa is a chronic socially debilitating disorder of unknown
      aetiology. Treatments include simple incision and drainage, excision and healing
      by secondary intention, spilt-skin grafting, and local-flap reconstructions. All
      of these methods can leave unsightly scars. Recurrence of the disease can be
      significantly reduced only by wide local excision of all the hair-bearing skin.
      Most methods involve repeated hospital admission, and leave contour defects in
      the upper arm and axilla. We describe a new method using double opposing V-Y
      perforator-based flaps to recreate the axillary contour after wide excision of
      the hair-bearing skin of the axilla. This method allows both axillae to be
      treated in a single stage, and represents a new alternative in the treatment of
      axillary hidradenitis suppurativa. Four patients are described: three underwent
      bilateral excision and reconstruction, while the fourth had a unilateral
      procedure. All patients had a single surgical procedure with no flap loss. The
      result following known reconstructive procedures is far from satisfactory: skin
      grafting leaves a divot deformity, and when a local flap, such as the posterior
      arm or thoracodorsal flap, is used it leaves a large bulky flap in the axilla. In
      our technique the flaps maintain the diamond shape of the axilla.

PMID- 11987946
TI  - Microvascular transfer-related abrogation of capillary flow motion in critically
      reperfused composite flaps.
AB  - Capillary flow motion is defined as rhythmic fluctuations of blood flow in the
      capillaries. Although critical perfusion has been demonstrated to induce
      capillary flow motion, little is known about the role of capillary flow motion in
      microvascular free flaps. The aim of this study was to elucidate the tissue
      confined incidence and consequence of capillary flow motion in microvascularly
      transferred composite flaps, using intravital fluorescence microscopy. In Wistar
      rats, transferred osteomyocutaneous flaps (n = 7), which were exposed to 1 h of
      ischaemia during the anastomotic procedure followed by 1 h of reperfusion, were
      subjected to critical perfusion by stepwise reduction of the femoral-artery blood
      flow to 0.15 ml min(-1), 0.10 ml min(-1) and 0.05 ml min(-1). Pedicled
      osteomyocutaneous flaps that were not subjected to ischaemia (n=8) served as
      controls. In pedicled flaps critical perfusion induced capillary flow motion in
      the muscle, but not in the skin, subcutis and periosteum. In these flaps, the
      functional capillary density was preserved in all tissues analysed, including the
      skeletal muscle. Additional sympathetic denervation of the pedicled flaps did not
      change the incidence or pattern of capillary flow motion. In contrast, after flap
      transfer capillary flow motion in muscle tissue did not occur during critical
      perfusion. As a consequence, a shutdown of perfusion of individual capillaries
      was observed, resulting in a significant reduction (P<0.05) in functional
      capillary density, not only in the subcutis, skin and periosteum but also in the
      muscle itself. Thus, our data suggest that the microcirculatory control of
      pedicled osteomyocutaneous flaps is preserved during critical perfusion by
      skeletal-muscle capillary flow motion, whereas this protective regulatory
      mechanism is lost during the initial reperfusion period after flap transfer,
      probably not because of denervation but because of surgery- and/or ischaemia
      reperfusion-associated injury.

PMID- 11987947
TI  - Viability of hypothermic preserved muscle determined by gene expression levels.
AB  - We report a muscle viability index (MVI) that reflects mRNA degradation. The
      viability of hypothermically preserved (48C) rat skeletal muscle was evaluated
      using this MVI. To evaluate the hypothermic ischaemic insult of the muscle, 21
      hind limbs of Fischer rats (three subgroups of seven limbs each) were
      hypothermically preserved for 1h, 3h and 6h, before harvesting the tibialis
      anterior muscle. To investigate reperfusion injury after hypothermic
      preservation, an additional 28 limbs were transplanted to recipient Fischer rats
      after hypothermic ischaemia for either 3h or 6h. The transplanted muscles were
      harvested on either day 3 or day 7 after transplantation. Seven fresh muscles
      were also harvested, and used as controls. In the 3h ischaemia group, the MVIs of
      both the hypothermic-ischaemia and the ischaemia-reperfusion subgroups were
      comparable to the controls. Likewise, there were no significant differences
      between the controls and the 6h hypothermic ischaemia and ischaemia-reperfusion
      subgroups. These results show that muscle viability is maintained with
      hypothermic preservation of up to 6h, and after reperfusion. Therefore, in
      clinical replantations the amputated extremity should be preserved under
      hypothermic conditions from the time of injury to the time of surgery.

PMID- 11987948
TI  - Pharmacological salvage of a combined distal bypass and free flap with catheter
      directed thrombolysis.
AB  - With recent improvements in microvascular techniques, the use of combined distal
      bypass and free-flap transfer has been advocated for salvaging the critically
      ischaemic limb in extreme conditions. Distal bypass, however, carries an inherent
      risk of graft failure due to thrombosis, and this may threaten the viability of
      the free flap and, indeed, the lower limb. We present the case of a 66-year-old
      man with acute-on-chronic ischaemia of his left leg and rectus abdominis free
      flap. Despite a prolonged ischaemic time of 72 h, both were successfully salvaged
      using catheter-directed recombinant tissue plasminogen activator. This is
      previously unreported in the literature.

PMID- 11987949
TI  - Autosomal dominant craniometaphyseal dysplasia with atypical features.
AB  - Craniometaphyseal dysplasia (CMD) is a rare genetic disorder of bone modelling
      characterised by hyperostosis and sclerosis of the craniofacial bones, and
      abnormal modelling of the metaphyses. Clinically, autosomal dominant (AD) CMD is
      characterised by facial distortion and cranial-nerve compression. The goals of
      surgical treatment for AD CMD are cosmetic recontouring of the sclerotic
      craniofacial bones, correction of nasal obstruction and correction or prevention
      of neurological manifestations. We describe the successful correction of AD CMD
      craniofacial manifestations in an individual with atypical findings, and outline
      an approach for correcting the craniofacial deformities associated with this rare
      disorder.

PMID- 11987950
TI  - Post-burn breast resurfacing using an abdominal full-thickness skin graft.
AB  - We describe a case of delayed resurfacing of the right breast using the abdominal
      skin as a full-thickness graft in a 38-year-old woman who sustained a scald
      injury in childhood. The postoperative results are shown.

PMID- 11987951
TI  - Diffuse hyperplastic oncocytosis of the parotid gland.
AB  - Oncocytic tumours rarely affect the major salivary glands, accounting for less
      than 1% of all salivary-gland tumours. The World Health Organisation
      classification groups these tumours into three principal types: diffuse
      oncocytosis, focal adenomatous oncocytic hyperplasia and oncocytoma. Diffuse
      hyperplastic oncocytosis is the rarest lesion: only six cases have been
      previously reported in the literature. This condition of putative hyperplastic
      pathogenesis follows a benign course, whereas oncocytomas may recur after
      excision. No metastatic dissemination or recurrence of diffuse hyperplastic
      oncocytosis has been reported. We present and discuss a new case of diffuse
      hyperplastic oncocytosis of the parotid gland.

PMID- 11987952
TI  - Lymphoedema of the eyelids.
AB  - Lymphoedema of the eyelids interfering with vision can be a very debilitating
      condition. The aetiology is frequently unknown. Successful treatment by debulking
      and skin grafting has been described in a few cases. We present a case of sudden
      onset of massive bilateral eyelid oedema, which was treated using staged
      debulking without skin grafting. However, the cosmetic result was poor in
      comparison with skin grafting, suggesting that skin grafting may be a better way
      of treating this difficult problem.

PMID- 11987953
TI  - Reconstruction of knee ligaments with a free tensor fascia lata myocutaneous flap
      transfer.
AB  - A 26-year-old woman suffered a grinding injury of the thigh and knee, resulting
      in the loss of a large amount of soft tissue and some of the femur. A
      contralateral tensor fascia lata myocutaneous free flap was used to reconstruct
      the soft tissues and the lateral ligament compartment around the knee. Later, a
      ceramic artificial bone was implanted. The patient was able to walk, and a stress
      radiograph showed that the implanted artificial bone and the knee joint were
      stable. There was no donor-site morbidity. The functional and cosmetic results
      were satisfactory.

PMID- 11987954
TI  - Reconstruction of a pulp defect using a free finger-pulp flap from a non
      replantable digit.
AB  - We report a case of finger-pulp reconstruction after traumatic multidigital
      amputation injury. A freefinger-pulp flap was raised from a non-replantable
      amputated digit and successfully transferred to provide a satisfactory well
      padded sensate fingertip with an excellent cosmetic appearance.

PMID- 11987955
TI  - Necrotising fasciitis in an infant with congenital insensitivity to pain
      syndrome.
AB  - We present a rare case of necrotising fasciitis in an infant with congenital
      insensitivity to pain syndrome. The aetiology, diagnosis and management of
      necrotising fasciitis in children are compared with those in adults. In contrast
      to adults, children affected by necrotising fasciitis are usually previously
      healthy and have no predisposing factors. Early diagnosis, intravenous
      antibiotics and aggressive surgical debridement are mandatory for an optimal
      outcome.

PMID- 11987956
TI  - Kaposiform haemangioendothelioma: case report and review of the literature.
AB  - Kaposiform haemangioendothelioma (KHE) is a rare vascular tumour, predominantly
      of infancy and early childhood, that has a close association with Kasabach
      Merritt syndrome. Despite benign histology, this tumour frequently behaves
      aggressively, causing significant morbidity and mortality as a result of the
      compression and invasion of surrounding structures as well as from associated
      haematological and lymphoproliferative syndromes. There is a need for a high
      index of suspicion when presented with large, enlarging or abnormal vascular
      lesions in infancy and, less commonly, in adulthood. An early diagnosis of KHE
      can lead to prompt treatment, which may be life saving. To date, there have been
      only four reported cases of KHE occurring in patients over the age of 18 years.
      We report an otherwise well 26-year-old woman who presented with a KHE of the
      left thigh, and briefly review the literature. We believe this to be the second
      reported case of KHE in the UK and the first in an adult patient.

PMID- 11987957
TI  - Subungual melanoma in situ: two independent streaks in one nail bed.
AB  - We report an unusual case of two nail-bed streaks under one nail, revealing
      melanoma in situ affecting the nail bed and plate, but not the nail fold. This
      unusual mode of presentation together with the absence of any nail-fold
      involvement has not been reported previously. We highlight the need for early
      histological assessment of nail-bed lesions and discuss subungual melanoma.

PMID- 11987958
TI  - Protecting patients and surgeons: implications of the Data Protection Act 1998 in
      plastic surgical practice.

PMID- 11987959
TI  - Anterior scoring for prominent ears: probably the Cloutier technique.

PMID- 11987960
TI  - Effective insulation of the cutting diathermy blade.

PMID- 11987961
TI  - Neonatal excision of minor congenital anomalies under local anaesthetic.

PMID- 11987962
TI  - The prevention of haematoma following rhytidectomy.

PMID- 11987963
TI  - Aesthetic complex reconstruction of the lower leg: application of a dermal
      substitute (Integra) to an adipofascial flap.

PMID- 11987964
TI  - Spontaneous bleeding following steroid injection and silicone-gel sheeting in a
      keloid scar.

PMID- 11987965
TI  - A simple modification of TRAM flap breast reconstruction.

PMID- 11987966
TI  - No-touch free-flap temperature monitoring.

PMID- 11987967
TI  - An aberrant lymph node containing metastatic melanoma.

PMID- 11987968
TI  - Sensory recovery after reconstruction of defects of long fingertips using the
      pedicled V flap.

PMID- 11987969
TI  - Failure to thrive in babies with cleft lip and palate.

PMID- 11987970
TI  - Consenting made easy: using a sticky label.

PMID- 11987971
TI  - The use of preoperative swabs in cleft lip and palate repair.

PMID- 11987972
TI  - Modified application of alginate dressings on graft donor sites.

PMID- 11987973
TI  - Infiltration of local anaesthetic using a tourniquet.

PMID- 11987974
TI  - Useful instrument for retracting a patient's tongue.

PMID- 11987975
TI  - Variant mattress suture for skin closure.

PMID- 11987976
TI  - Sterilisation of Elastoplast adhesive tape.

PMID- 11987977
TI  - The bra-strap injury: should men have lessons?

PMID- 11987979
TI  - Fas-ligand--iron fist or Achilles' heel?
AB  - Experimental and physiological expression of the pro-apoptotic molecule Fas
      ligand can induce inflammation under certain conditions. Discussed here are the
      experimental situations, possible mechanisms, and pathways that mediate this
      response.

PMID- 11987980
TI  - Millennium Award. Proteomics for the development of DNA tolerizing vaccines to
      treat autoimmune disease.
AB  - Autoimmune disease affects 3% of the world population, yet current therapies that
      globally suppress immune function are inadequate. Tremendous need exists for
      specific and curative therapies, and we describe a strategy for development of
      antigen-specific therapies that inactivate pathogenic lymphocytes causing tissue
      injury. Major barriers to development of antigen-specific therapies for T-cell
      mediated autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis,
      and autoimmune diabetes, include (i) lack of knowledge of the specificity of
      autoimmune responses, for which proteomic technologies represent powerful tools
      to identify the self-protein targets of the autoimmune response, and (ii) lack of
      methods to induce specific immune tolerance, for which DNA tolerizing vaccines
      represent a promising strategy. We termed our approach Reverse Genomics: use of
      the proteomics-determined specificity of the autoantibody response to develop and
      select DNA tolerizing vaccines. Studies performed using animal models for
      multiple sclerosis and autoimmune diabetes support our Reverse Genomics approach.
      Through integration of proteomics with specific tolerizing therapies, we are
      developing a comprehensive approach to treat human autoimmune disease.

PMID- 11987981
TI  - Immune function in patients with rheumatoid arthritis treated with etanercept.
AB  - Etanercept, a recombinant human tumor necrosis factor (TNF) inhibitor that binds
      both soluble and cell-bound TNF, has been shown to reduce disease activity and
      inhibit joint destruction when administered to patients with rheumatoid arthritis
      (RA). Because TNF receptors are found on many types of cells that modulate the
      immune response, we evaluated the general immune function of a subset of RA
      patients in a blinded clinical study. No significant differences were seen
      between patients treated with etanercept or placebo in the surface antigen
      phenotypes of peripheral blood leukocytes, T cell proliferative responses,
      neutrophil function, delayed-type hypersensitivity (DTH) reactions, serum
      immunoglobulin levels, or incidence of infections. Although this observational
      study was relatively small and could detect only major changes in immunological
      status, the stability of immune function over time in patients receiving
      etanercept corroborates the findings in clinical studies, which suggest that
      etanercept does not alter overall global immune function.

PMID- 11987982
TI  - Human B lymphocytes and B lymphomas express PPAR-gamma and are killed by PPAR
      gamma agonists.
AB  - This paper evaluates the expression and functional significance of PPAR-gamma on
      human B cells. Recent interest in PPAR-gamma has focused on its adipogenic
      effects on non-bone marrow-derived cells. PPAR-gamma agonists also have been
      proposed as anti-inflammatory agents owing to inhibition of NF-kappa B
      activation. We report herein the first study evaluating PPAR-gamma expression and
      functional significance in human B lineage cells. Interestingly, normal human B
      cells and a variety of B lymphoma cells (e.g., Daudi, Ramos, and Raji) express
      PPAR-gamma protein as determined by immunocytochemistry. The expression of 80-kDa
      PPAR-gamma on human B lymphocytes and B lymphomas was confirmed by Western blot
      analysis. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), a natural PPAR-gamma
      agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal
      and malignant B cells as shown by [(3)H]thymidine and MTT assays. Only PPAR-gamma
      agonists (thiazolidinediones) and not PPAR-alpha agonists mimicked the effect of
      15d-PGJ(2) on B lineage cells, indicating that the mechanism by which 15d-PGJ(2)
      negatively affects B lineage cells involves, in part, PPAR-gamma. The mechanism
      whereby PPAR-gamma agonists induce cytotoxicity is via apoptosis as shown by
      Annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL
      assay. This is the first study evaluating PPAR-gamma expression and its
      significance on human B lymphocytes. PPAR-gamma agonists may serve as a
      counterbalance to the stimulating effects of other prostaglandins, namely PGE(2),
      which promotes B cell immunoglobulin class switching. Finally, the use of
      prostaglandins such as 15d-PGJ(2) and synthetic PPAR-gamma agonists to induce
      apoptosis in B lineage cells may lead to the development of novel therapies for
      potentially fatal B lymphomas.

PMID- 11987983
TI  - Absence of memory B cells in patients with common variable immunodeficiency.
AB  - The molecular basis of common variable immunodeficiency (CVID) is unknown. To
      assess humoral immunity in CVID, we selected 24 patients with early or late onset
      of disease. X-linked agammaglobulinemia (XLA), X-linked hyper-IgM syndrome
      (XHIM), and non-XHIM were excluded based on clinical phenotype, assessment of the
      immune response, presence of Bruton's tyrosine kinase (Btk) in monocytes or
      platelets, and normal expression of CD40 ligand by activated T cells. The number
      of circulating B cells was within the normal range or reduced. IgD(-) CD27(+)
      memory B cells were markedly reduced or absent in all 24 patients and IgD(+)
      CD27(+) B cells were diminished in 8 patients. Circulating B cells from all 6
      patients examined, including CVID patients with IgD(+) CD27(+) cells, failed to
      undergo somatic hypermutation in immunoglobulin-variable (V)-region genes,
      similar to cord blood B cells. B cells from CVID patients produced IgM and IgG,
      but not IgA upon the engagement of Ig receptor and CD40 in the presence of IL-2
      and IL-10. B cells from all but 5 patients secreted IgE when stimulated by CD40
      crosslinking in the presence of IL-4. The observation of defective memory B cells
      with abnormal cell marker expression and function demonstrates that naive CVID B
      cells including those expressing IgD(+) CD27(+), in analogy to cord blood and
      hyper-IgM syndrome B cells, may be responsible for their failure to differentiate
      into plasma cells and to produce high-affinity antibodies of different isotypes.

PMID- 11987984
TI  - A complement-dependent model of thrombotic thrombocytopenic purpura induced by
      antibodies reactive with endothelial cells.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an immunologically mediated disease
      characterized by thrombocytopenia, hemolytic anemia, and pathologic changes in
      various organs, including the kidney, which are secondary to widespread
      thromboses. Central to TTP is platelet activation, which may occur from a variety
      of mechanisms, including endothelial cell activation or injury. In this study,
      injection of K6/1, a monoclonal antibody with widespread reactivity toward
      endothelia, led to dose-dependent thrombocytopenia in rats. This was magnified if
      animals were preimmunized with mouse IgG, thereby resulting in an accelerated
      autologous phase of injury. In this setting, significant anemia also resulted.
      Rats injected with K6/1 developed renal injury, consisting of tubular damage and
      glomerular thrombi. Thrombocytopenia and renal morphological abnormalities were
      eliminated if animals were complement depleted with cobra venom factor prior to
      K6/1 injection and worsened when the activity of the ubiquitous complement
      regulator Crry was inhibited with function-neutralizing antibodies. Therefore, we
      have developed a complement-dependent model of TTP in rats by injecting
      monoclonal antibodies reactive with endothelial cells. Antibody-directed
      complement activation leads to stimulation of platelets, through direct
      interactions with complement fragments and/or indirectly through endothelial cell
      activation or injury, with the subsequent development of TTP.

PMID- 11987985
TI  - Aberrant expression of the costimulatory molecule CD40 ligand on monocytes from
      patients with systemic lupus erythematosus.
AB  - CD40 ligand (CD40L, CD154) is overexpressed on T and B cells in systemic lupus
      erythematosus (SLE). Monocytes have been shown to contribute to immune-mediated
      pathology in SLE and to express CD40L under certain conditions. Therefore, we
      studied CD40L expression on lupus monocytes ex vivo, as well as after activation
      in vitro. A highly significant sevenfold increase in the frequency of CD40L
      expressing peripheral monocytes from 23 SLE patients, compared to 16 healthy
      individuals (mean percentage of CD40L(+)CD14(+) among CD14(+) cells, 11.7 versus
      1.6), was found by flow cytometry. Increased CD40L expression on monocytes
      correlated significantly with disease activity, elevated gamma-globulin serum
      levels, as well as increased CD40L expression on T cells. CD40L expression by
      lupus monocytes was verified at both the mRNA and protein levels, while LPS
      stimulation was found to upregulate CD40L mRNA accumulation and surface protein
      expression. CD40L expression on activated lupus monocytes within anti-CD3
      stimulated, mononuclear cell cultures was also enhanced compared to control
      derived monocytes. These novel findings underscore the multiplicity of pathways
      through which monocytes may contribute to SLE pathology and suggest that T cell
      independent CD40L-mediated cell to cell interactions may be also involved in
      humoral immune activation in SLE.

PMID- 11987986
TI  - Alterations in serum anti-alpha-galactosyl antibodies in patients with Crohn's
      disease and ulcerative colitis.
AB  - Anti-galactosyl alpha1-3-galactosyl (anti-Gal) is a natural serum antibody
      abundantly produced in humans in response to immune stimulation by enteric
      bacteria. Marked elevation of its titer has been detected in parasitic diseases
      and in some autoimmune disorders. Because persistent intestinal infection and
      defective mucosal barrier have been suggested as potential etiologic agents of
      inflammatory bowel disease, the aim of this study was to analyze the sera levels
      of anti-Gal antibodies in patients with Crohn's disease and ulcerative colitis.
      An ELISA assay was performed to analyze circulating antibody using the
      disaccharide Gal (alpha 1-3)Gal coupled to human serum albumin as antigen and
      alkaline phosphatase-conjugated rabbit anti-human immunoglobulin G, A, M as
      antibody. Immunoglobulin classes were assayed using class-specific antibodies.
      The optical densities of sera from Crohn's disease (1.83 +/- 0.63) and ulcerative
      colitis (1.45 +/- 0.7) were significantly higher (P < 0.0001 and P < 0.0005,
      respectively) than those of the control group (0.97 +/- 0.39). In Crohn's disease
      the increase was distributed among the three immunoglobulin classes; in
      ulcerative colitis a significant increase was observed only for immunoglobulin A.
      The increased levels of circulating antibodies against Gal (alpha 1-3)Gal in the
      presence of intestinal bacterial strains expressing antigenic epitopes and
      breakdown of mucosal barrier could contribute to the dysregulated immune response
      observed in inflammatory bowel disease.

PMID- 11987987
TI  - Induction of biologically active antineutrophil cytoplasmic antibodies by
      immunization with human apoptotic polymorphonuclear leukocytes.
AB  - Translocation of intracellular components to the cell surface during the priming
      or apoptosis of polymorphonuclear leukocytes (PMN) is an important mechanism for
      interaction of antineutrophil cytoplasmic antibodies (ANCA) with these antigens.
      To test the capacity of apoptotic PMN to trigger production of ANCA, six groups
      of mice were immunized with either live or apoptotic lymphocytes, or with live,
      apoptotic, formalin-fixed, or lysed PMN. Mice immunized with both live and
      apoptotic neutrophils developed high titers of antibodies which gave a granular
      cytoplasmic immunofluorescent pattern. These antibodies were specific for
      lactoferrin and myeloperoxidase. Following a second intravenous infusion of
      apoptotic PMNs, mice developed anti-PR3 antibodies. Vasculitis lesions were not
      found in mice which developed ANCA. The ANCA-containing IgG fraction induced
      superoxide production by human PMNs. These results support the hypothesis that
      neutrophil-specific antigens presented on the cell membranes of apoptotic PMN may
      induce ANCA in the proper conditions.

PMID- 11987988
TI  - Abnormal B cell differentiation in primary Sjogren's syndrome results in a
      depressed percentage of circulating memory B cells and elevated levels of soluble
      CD27 that correlate with Serum IgG concentration.
AB  - The percentage of CD27(+) B cells in peripheral blood (PB) of patients with
      primary Sjogren's syndrome (pSS) is significantly decreased compared to normals.
      In contrast, serum levels of the soluble form of CD27 (sCD27) are significantly
      higher in pSS patients, with a strong positive correlation between sCD27 and
      serum IgG levels. In vitro experiments demonstrate that normal B cells cultured
      under conditions driving plasma cell differentiation result in the production of
      substantial amounts of sCD27. Analyses of V(H)-region genes from sorted CD27(+)
      and CD27(-) B cells from pSS patients confirm that the CD27(+) population
      corresponds to the somatically mutated memory compartment, as in healthy
      individuals. Together our data indicate that in pSS, there is an abnormal
      differentiation of B cells to plasma cells resulting in a depression of the
      circulating memory B-cell pool and the release of significant amounts of sCD27
      and IgG.

PMID- 11987989
TI  - Role of RANTES in the development of autoimmune tissue injuries in MRL-Fas lpr
      mice.
AB  - MRL-Fas lpr mice spontaneously develop a severe autoimmune disease closely
      resembling human SLE. To investigate the possible role of RANTES in autoimmune
      tissue injuries, we have constructed RANTES-deficient MRL-Fas lpr mice by gene
      targeting. In the RANTES-deficient mice, axillary lymph nodes were significantly
      reduced in size compared with those of RANTES-intact mice. Flow cytometric
      analysis revealed that double-negative (DN) T cells were significantly reduced.
      Image analyzer showed that cell-infiltrated areas in peribronchial lesions were
      decreased in the lung of RANTES-deficient MRL-Fas lpr mice. Furthermore, we
      detected continuous expression of RANTES mRNA in the lung of MRL-Fas lpr mice. In
      contrast, the degree of histological renal injuries and survival rate was similar
      in both genotypes. We speculate that RANTES is involved in the development of
      peribronchial pulmonary lesions in MRL-Fas lpr mice. Further studies using RANTES
      deficient mice might contribute to the elucidation of the role of RANTES in
      autoimmune tissue injuries.

PMID- 11987990
TI  - Spontaneous secretion of immunoglobulins and anti-HIV-1 antibodies by in vivo
      activated B lymphocytes from HIV-1-infected subjects: monocyte and natural killer
      cell requirement for in vitro terminal differentiation into plasma cells.
AB  - Peripheral blood mononuclear cells from HIV-1-infected subjects secrete
      spontaneously in vitro immunoglobulins (Ig) and anti-HIV-1 antibodies (Ab).
      Purified B lymphocytes secrete only minute amounts of Ig and anti-HIV-1 Ab
      compared with unfractionated cells. Monocytes and natural killer cells enhanced
      both secretions by cell-to-cell contacts, involving adhesion and CD27, CD80
      costimulatory molecules and IL-6. Cell interactions prolonged the survival and
      allowed the terminal maturation of in vivo activated B cells. The secreting cell
      precursors were highly differentiated B cells expressing a broad diversity of
      maturation markers (CD27(+), CD38(+), CD20(+/-), CD37(+/-), CD71(+/-), HLA-DQ(+/
      ), sIg(+/-)) but not sIgD, CD28, or CD40. This phenotype and the cytologic aspect
      of purified B cells suggest that these cells are early plasma cells originated
      from germinal center. Ex vivo secreting peripheral B cells had probably gone
      beyond the CD40/CD40 ligand interaction; then following CD28/CD80 and CD27/CD27
      ligand (CD70) interactions in the presence of IL-6, they achieved in vitro their
      differentiation into plasma cells.

PMID- 11987991
TI  - Nucleation and Crystal Growth in a Vitrification Solution Tested for Organ
      Cryopreservation by Vitrification.
AB  - Nucleation and crystal growth are investigated for vitrification solution VS41A
      (dimethyl sulfoxide, formamide, and 1,2-propanediol) in an aqueous carrier
      solution giving, when added to these three cryoprotectants, a concentration of
      other solutes in the whole solution the same as that in Euro-Collins, with a 55%
      (w/v) cryoprotectant concentration. This concentration is assumed to achieve
      physical properties under 1 atmosphere similar to those of solution VS4 used
      under 1000 atmospheres. The thermal range and the kinetics of nucleation and
      crystal growth are investigated by DSC through different thermal treatments. It
      is found that the nucleation thermal range is below -90 degrees C and that of
      crystal growth is above -85 degrees C for a relatively long experimental time.
      The nucleation density is also studied through direct observations by
      cryomicroscopy and is related to the amount of crystallization calorimetrically
      recorded. The effect of storage below the glass transition shows the possibility
      of a slow increase in nucleation below the glass transition, as already observed
      by other authors for different aqueous solutions. Isothermal crystallization is
      analyzed within the Johnson-Mehl-Avrami model for temperatures above -75 degrees
      C. The corresponding samples have been cooled and warmed at the same rate of 40
      degrees C/min and calculations give, at constant nuclei numbers, an activation
      energy of 9.3 +/- 0.3 kcal/mol and the Avrami exponent n = 2.2 +/- 0.05. This
      shows a two-dimensional crystal growth as observed by cryomicroscopy. The
      estimated critical warming rate relevant to the preservation of rabbit kidneys by
      vitrification is 270 degrees C/min with or without an increase in the nucleus
      density during storage. The present results support the possibility of using VS4
      solution for vitrification of rabbit kidneys if pressure is not a limiting
      factor. Copyright 1993, 1999 Academic Press.

PMID- 11987992
TI  - Cold-Hardiness and Supercooling Capacity in Diapausing and Nondiapausing Stages
      of the Cabbage Root Fly Delia radicum.
AB  - Supercooling point (SCP) values and cold-hardiness were measured in individual
      ontogenetic stages of Delia radicum (Diptera:Anthomyiidae) in various
      physiological states (winter diapause, summer quiescence, and normal
      development). Winter diapause-destined mature third-instar larvae had a lower SCP
      (-9.9 degrees C) than their nondiapause counterparts (-5.2 degrees C), and more
      of them survived exposure to -10 degrees C for 5 h to pupariation and adult
      emergence. Values of SCPs were equal in both diapause and nondiapause states of
      prepupal and pupal stages. The lowest SCP (ca. -20 degrees C) was found in the
      stage of phanerocephalic pupa (PCP) regardless of the physiological state. The
      cold-hardiness of PCP corresponded with a low SCP value only in diapausing pupae
      stored for 80 days at 3 degrees C and in pupae which had terminated their
      diapause and whose further development was inhibited by storage at low
      temperatures (3 degrees C). Such pupae survived exposure to temperatures close to
      their SCP (14 days at -17 degrees C). However, this high cold-hardiness was only
      acquired after some time and/or exposure to 3 degrees C, as the PCP at the
      beginning of diapause showed significantly impaired cold-hardiness despite the
      fact that their SCP was low. The cold-hardiness of nondiapausing PCP did not
      correspond at all to that of low SCP, as no pupa survived the exposure to -17
      degrees C for 1 day; survival rates at temperatures of -13.5 and -10 degrees C
      were also remarkably lower than those in diapausing pupae. Cold-hardiness in D.
      radicum was closely connected with the diapause syndrome but the changes in SCP
      value corresponded rather with the ontogeny of this insect. Copyright 1993, 1999
      Academic Press.

PMID- 11987993
TI  - Investigation of Lactobacilli Strains during Lyophilization.
AB  - The Freezing Points of three lactobacilli strains cultivated in skim milk and MRS
      broth were determined. Their survival was analyzed after lyophilization. A
      maximal preservation of the cell number of the R1 strain was found. The
      fermentation activity of the laclobacilli was investigated before and after
      lyophilization in order to characterize their species identification. Copyright
      1993, 1999 Academic Press.

PMID- 11988016
TI  - Interaction of a paraneoplastic cerebellar degeneration-associated neuronal
      protein with the nuclear helix-loop-helix leucine zipper protein MRG X.
AB  - Paraneoplastic cerebellar degeneration-associated antigen PCD17/cdr2 is a
      neuronal protein expressed predominantly in the cytoplasm of cerebellar Purkinje
      cells. The biological activities of this protein are not known; however, the
      presence of a leucine zipper motif in its amino acid sequence suggests that this
      protein might interact with other proteins harboring a leucine zipper motif. In
      this study we found by means of a yeast two-hybrid system, ligand overlay assay,
      and co-immunoprecipitation assay that PCD17 interacts with a nuclear helix-loop
      helix leucine zipper protein, MRG X. Overexpression of MRG X in T98G glioblastoma
      cells by transfection caused abnormal morphological changes in the nucleus and
      induced cell death. On the other hand, coexpression of PCD17 with MRG X prevented
      nuclear morphological changes and cell death in T98G cells. MRG X, which is
      thought to be functionally related to the cell cycle and cell growth, may be
      regulated by PCD17/cdr2 in Purkinje cells.

PMID- 11988017
TI  - Anterograde transport and trophic actions of BDNF and NT-4/5 in the developing
      rat visual system.
AB  - During development the viability of immature neurons may depend upon retrograde,
      anterograde, or paracrine trophic support. Using (125)I-labeled peptides we show
      that there is substantial and rapid anterograde transport of brain-derived
      neurotrophic factor (BDNF) and, to a lesser extent, neurotrophin-4/5 (NT-4/5) to
      central visual target areas in the neonatal rat brain. Six hours after unilateral
      intraocular injection, all retinorecipient regions in the thalamus and midbrain
      are heavily labeled. Intraocular application of physiologically relevant doses of
      neurotrophin has a marked effect on cells in the developing superior colliculus
      (SC): 24 h postinjection of BDNF or NT-4/5, the number of pyknotic profiles in
      the contralateral superficial SC significantly decreases, while total cell
      numbers increase relative to ipsilateral SC. This increase is primarily
      associated with neurons. The data support the hypothesis that BDNF and NT-4/5 are
      anterograde survival factors for postsynaptic cells in the developing rat SC.

PMID- 11988018
TI  - A P element with a novel fusion of reporters identifies regular, a C2H2 zinc
      finger gene downstream of the circadian clock.
AB  - Elucidating the mechanisms that link the circadian pacemaker to the timing of
      behaviors it controls is one of the greatest challenges in circadian biology. We
      report the generation of a P element, Pluc+, containing a novel reporter fusion.
      Our fusion reporter capitalizes on the use of luciferase bioluminescence to
      easily analyze temporal expression as well as the strength of myc epitopes and
      GFP to identify spatial expression. Using Pluc+ we have identified and
      characterized a novel C2H2 zinc-finger gene, regular (rgr), that cycles
      circadianly in phase with period (per) gene expression, but shifts to light-dark
      regulation in Clk(Jrk) mutant flies. By following myc expression of the Pluc+
      reporter, we demonstrate that Rgr is expressed in a discrete number of neurons in
      the brain which overlap with axons expressing pigment-dispersing factor.

PMID- 11988019
TI  - Retinal pathology and function in a Cln3 knockout mouse model of juvenile
      Neuronal Ceroid Lipofuscinosis (batten disease).
AB  - Batten disease or JNCL, is the juvenile form of Neuronal Ceroid Lipofuscinosis
      (NCL) an autosomal recessive neurodegenerative disorder. Since retinal
      degeneration is an early consequence of Batten disease, we examined the eyes of
      Cln3 knockout mice (1-20 months of age), along with heterozygotes and appropriate
      controls, to determine whether or not the Cln3 defect would lead to
      characteristic retinal degeneration and visual loss. Accumulation of
      autofluorescent material and intracellular inclusions were markedly increased in
      Cln3 knockout retinal ganglion cells, as well as most other nuclear layers. Nerve
      fiber density was also significantly decreased in Cln3 knockout retinae.
      Apoptosis was observed in the photoreceptor layer of Cln3 knockout. However, the
      degree of retinal degeneration up to age 20 months was not extensive. Fundus
      examinations of Cln3 knockout mice showed no significant abnormalities, while
      electroretinograms remained robust through 11 months of age. In summary, it
      appears that accumulation of autofluorescent material, carbohydrate storage
      material, as well as apoptotic cell death are retinal manifestations of the Cln3
      defect that do not appear to extinguish retinal function in this mouse model of
      Batten disease.

PMID- 11988020
TI  - Opposing functions of GDNF and NGF in the development of cholinergic and
      noradrenergic sympathetic neurons.
AB  - We identified a population of mature sympathetic neurons in which Ret, the
      receptor for glial cell line-derived neurotrophic factor (GDNF), is coexpressed
      with the neurotrophin-3 (NT3) receptor TrkC and choline acetyltransferase. In a
      complementary population the nerve growth factor receptor TrkA is coexpressed
      with the norepinephrine transporter. In accordance with these in vivo results,
      GDNF and neurturin promote the expression of cholinergic marker genes in
      sympathetic chain explants, similar to NT3 and ciliary neuronotrophic factor
      (CNTF). To define intracellular signaling mechanisms commonly activated by NT3,
      GDNF, or CNTF to promote cholinergic differentiation, we have analyzed the
      activation of intracellular signaling cascades. Signal transducer and activator
      of transcription-3 (STAT3) was strongly activated by CNTF but not by GDNF or NT3
      and hence is not essential for cholinergic differentiation. We conclude that
      cholinergic properties can be regulated by neurotrophic factors from three
      different protein families, whereas noradrenergic properties are promoted by NGF.

PMID- 11988021
TI  - Modulation of agrin binding and activity by the CT and related carbohydrate
      antigens.
AB  - Agrin is a nerve-derived signal that is essential for the proper organization of
      postsynaptic acetylcholine receptors (AChRs) at the vertebrate neuromuscular
      junction. It is likely that carbohydrates play a significant role in regulating
      agrin activity, as agrin binds multiple glycan structures and is itself a highly
      glycosylated protein. Here we provide support for this contention by showing that
      agrin can be modified with the CT antigen, a carbohydrate structure expressed at
      the neuromuscular junction, and by describing the resulting changes in agrin
      binding to neoglycoconjugates and cultured myotubes, as well as changes in agrin
      dependent AChR clustering. Glycosylation of agrin with the CT antigen required
      the mucin domain and the dystroglycan/heparin-binding domain. The presence of the
      mucin domain lowered agrin binding to several N-acetyllactosaminyl-containing
      saccharides and C2 myotubes and lowered agrin activity in AChR clustering.
      Glycosylation of agrin with the CT antigen, by contrast, increased agrin binding
      to myotubes and potentiated its AChR clustering activity at subsaturating
      concentrations. Last, sialylated and nonsialylated variants of N
      acetyllactosamine differentially modulated AChR clustering and agrin activity,
      and these changes correlated with the ability of MuSK, an agrin-stimulated
      kinase, to bind to these structures. These experiments demonstrate that the
      glycosylation state of agrin affects its activity and suggest a role for the CT
      antigen in modulating agrin function.

PMID- 11988022
TI  - Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium
      signaling.
AB  - Calsenilin (also called DREAM and KChIP3), a member of the neuronal calcium
      sensor family, was isolated in a yeast two-hybrid screen using an apoptotic
      domain of presenilin 2 as bait. Calsenilin is a cytoplasmic protein, but
      interacts with the COOH-termini of both presenilin 1 and presenilin 2 at the
      endoplasmic reticulum and the Golgi apparatus. In this study, we have
      investigated calsenilin's effect on apoptosis. In stable neuroglioma cell lines,
      we observed that calsenilin enhances apoptosis in response to serum withdrawal or
      thapsigargin. Consistent with these observations, caspase and apparently calpain
      activities were increased during apoptosis in calsenilin-overexpressing cells.
      Moreover, using calcium imaging we were able to show that cells treated with
      thapsigargin released more calcium from intracellular stores when calsenilin was
      overexpressed. Taken together, these data suggest that calsenilin causes cells to
      be more susceptible to apoptotic triggers, possibly by altering calcium dynamics.

PMID- 11988025
TI  - Neonatal nutrition.

PMID- 11988023
TI  - Global analysis of gene expression patterns in developing mouse neocortex using
      serial analysis of gene expression.
AB  - Molecular inventories of the developing mouse neocortex before and after birth
      were generated using the global gene expression profiling tool serial analysis of
      gene expression (SAGE). Libraries were generated from embryonic day 15 and
      postnatal day 1 mouse neocortex and more than 40,000 tags were collected (20,211
      and 22,001 tags, representing 11,706 and 12,402 transcripts, respectively).
      Comparison of the two libraries resulted in the identification of 321 transcripts
      that were differentially expressed (P < 0.05). Differential expression was
      independently verified for selected genes by Northern blotting, and in situ
      hybridization revealed spatial expression patterns in the neocortex.
      Differentially expressed transcripts included genes known to be important in
      neocortical development (e.g., brain factor 1, neuroD2, and Id2), genes not
      previously associated with neocortical development (such as brahma-related gene
      1, receptor for activated C-kinase I, hypermethylated in cancer 2, and Evi9), and
      genes of unknown identity or function.

PMID- 11988026
TI  - Determination of nutritional requirements in preterm infants, with special
      reference to 'catch-up' growth.
AB  - The usual recommendation for feeding preterm infants is to provide sufficient
      nutrients to support rates of growth and nutrient accretion equal to intrauterine
      rates. However, most preterm infants don't tolerate feedings immediately and,
      therefore, incur significant deficits prior to achieving sufficient intake to
      support growth. Furthermore, unless they receive nutrient intakes in excess of
      those usually recommended, they will be smaller than a fetus of the same
      postmenstrual age at discharge and remain smaller for some time thereafter. The
      consequences of these early deficits are not known with certainty but there is
      some evidence that they should be repleted as soon as possible. This requires a
      redefinition of requirements to include those for both normal growth and catch-up
      growth. Strategies for doing so include: more aggressive early parenteral
      nutrition to reduce the magnitude of early losses; greater enteral intakes of
      protein, and, perhaps, other nutrients once enteral feedings are tolerated; and
      more attention to nutrition post-discharge. Of these, the latter is somewhat
      problematic. This is because there seems to be a finite period - perhaps as brief
      as a few weeks - during which response to increased nutrient intake occurs. Firm
      data are limited, but those available suggest that current nutritional management
      of preterm infants can be improved. Whether this will have long-term benefits
      remains to be determined.

PMID- 11988027
TI  - Protein and energy requirements in preterm infants.
AB  - Although protein and energy requirements in healthy growing and enterally fed
      infants are relatively well established, the nutritional requirements of
      extremely low birth weight infants are considerably less certain. New and
      emerging data in ELBW infants suggest high rates of energy expenditure and
      protein losses, which results in significant nutritional deficits and high rates
      of growth failure. Based on the limited and incomplete available data, energy
      intakes of 125-130 kcal/kg/d and protein intakes of 3.5-4 g/kg/d appear to be
      necessary to produce normal growth in ELBW infants. Although these intakes may be
      difficult to achieve in clinical practice, there is clear evidence that
      aggressive early nutrition can improve growth outcomes in these infants.

PMID- 11988028
TI  - Nutritional assessment in preterm infants with special reference to body
      composition.
AB  - In recent years, improvements in care have significantly improved survival in
      preterm and, particularily, the very low birth weight infant (VLBW). While
      immediate survival can be directly related to pulmonary maturity, several studies
      stress the importance of timely and adequate nutrition in these high-risk infants
      on a short- and long-term [1]. Yet, nutritional support remains a very
      controversial issue in these high-risk infants. Early provision of adequate
      intakes may be limited by clinical instability and immaturity. At the same time,
      nutritional requirements and methods of nutritional assessment are not well
      defined. The aim of this paper is to outline some of the methods used during
      nutritional assessment in preterm infants with special reference to the
      measurement of body composition.

PMID- 11988029
TI  - Randomized clinical trials in infancy: methodologic issues.
AB  - Randomized clinical trials of early nutritional interventions in infants are
      necessary to establish safety and efficacy of supplementation of infant formulas
      with LCPUFAS for term and preterm infants. Such trials pose significant
      methodologic difficulties when applied to infants because of the rapidly changing
      development of the infant's central nervous system and its interdependence with
      multiple environmental factors. Current assessments of infant cognitive
      development in the first year of life lack stability and predictive relationships
      to later outcomes. Thus, intervention trials need to extend beyond the first two
      years of life. Small sample sizes, high attrition rates, and lack of attention to
      confounding variables known to be related to child outcomes are additional
      problems in the majority of studies to date, especially for preterm populations.
      Attention to selection and attrition biases and the roles of mediating and
      moderating factors in affecting intervention effects are also necessary to
      determine the benefits vs risks of LCPUFA supplementation of infant formula.

PMID- 11988030
TI  - Early aggressive nutrition in preterm infants.
AB  - Increasingly, neonatologists are realizing that current feeding practices for
      preterm infants are insufficient to produce reasonable rates of growth, and
      earlier and larger quantities of both parenteral and enteral feeding should be
      provided to these infants. Unfortunately, there is very little outcome data to
      recommend any particular nutritional strategy to achieve better growth. Instead,
      the rationale for feeding regimens in many nurseries has been quite variably
      extrapolated from animal data and human studies conducted in gestationally more
      mature and/or stable neonates. Additionally, there are no well-controlled,
      prospective studies that validate any nutritional regimen for the very preterm
      and or sick, unstable neonate. The goal of this review is to present available
      data to help define the risks and benefits of early parenteral and enteral
      nutrition, particularly in very preterm neonates, concluding with a more
      aggressive approach to feeding these infants than has been customary practice.

PMID- 11988031
TI  - Feeding methods for the preterm infant.
AB  - As more very immature preterm infants survive, provision of enteral feedings has
      become a major focus of concern. Although many aspects of gastrointestinal
      function are immature in the preterm infant, the ability of the preterm neonate
      to process and absorb enteral nutrients appears to be adequate enough to sustain
      nutritional needs. Few prospective randomized trials have compared the efficacy
      of different feeding methods. However, some studies have compared differing
      routes of feeding, rates of feeding, and volume of feeding. The ability to
      successfully digest enteral feedings may be inhibited or enhanced by
      pharmacological agents. The need to modify a feeding strategy can be monitored by
      tracking several measurements prospectively. Finally, there is a need to assess
      ongoing dietary needs of preterm infants for discharge planning.

PMID- 11988032
TI  - Neonatal iron nutrition.
AB  - Preterm infants are prone to iron deficiency. Their total body iron content at
      birth is low and gets further depleted by clinical practices such as
      uncompensated phlebotomy losses and exogenous erythropoietin administration
      during the neonatal period. Early iron deficiency appears to adversely affect
      cognitive development in human infants. To maintain iron sufficiency and meet the
      iron demands of catch-up postnatal growth, iron supplementation is prudent in
      preterm infants. A dose of 2-4 mg/kg/day is recommended for preterm infants who
      are fed exclusively human milk. A dose of 6 mg/kg/day or more is needed with the
      use of exogenous erythropoietin or to correct preexisting iron deficiency.
      However, due to the poor antioxidant capabilities of preterm infants and the
      potential role of iron in several oxidant-related perinatal disorders,
      indiscriminate iron supplementation should be avoided.

PMID- 11988033
TI  - Docosahexaenoic acid and arachidonic acid in infant development.
AB  - Docosahaxaenoic acid and arachidonic acid are highly concentrated in the central
      nervous system. The amount of these fatty acids in the central nervous system
      increases dramatically during the last intrauterine trimester and the first year
      of life. A central question of research conducted during the past 20 years is if
      the essential fatty acid precursor of docosahexaenoic acid is sufficient to
      achieve optimal DHA accumulation in the central nervous system and, therefore,
      infant development. The important role of non-human primate studies in
      characterising the behavioral effects of n-3 essential fatty acid deficiency and
      subsequent low brain DHA accumulation, the difference between essential fatty
      acid deficiencies and conditional deficiencies of docosahexaenoic acid and
      arachidonic acid, and the evidence that human infants have a conditionally
      essential need for docosahexaenoic acid and, perhaps, for arachidonic acid are
      summarised. The current suggestive evidence for several possible mechanisms
      underlying behavioral effects are also provided.

PMID- 11988037
TI  - A piece of my mind: body English.

PMID- 11988038
TI  - Alzheimer disease.

PMID- 11988039
TI  - Cutting edge debate: what training do skin surgeons need?

PMID- 11988040
TI  - CDC campaign targets antimicrobial resistance in hospitals.

PMID- 11988045
TI  - From the World Health Organization. Afghanistan: rebuilding an health system.

PMID- 11988046
TI  - Sildenafil and physical exertion in men with coronary artery disease.

PMID- 11988049
TI  - Hormone replacement therapy and risk of breast cancer.

PMID- 11988050
TI  - Hormone replacement therapy and risk of breast cancer.

PMID- 11988052
TI  - Early ischemic changes on computed tomography in patients with acute stroke.

PMID- 11988054
TI  - Prevalence of untreated sexually transmitted disease.

PMID- 11988055
TI  - Prevalence of untreated sexually transmitted disease.

PMID- 11988057
TI  - The association between duration of breastfeeding and adult intelligence.
AB  - CONTEXT: A number of studies suggest a positive association between breastfeeding
      and cognitive development in early and middle childhood. However, the only
      previous study that investigated the relationship between breastfeeding and
      intelligence in adults had several methodological shortcomings. OBJECTIVE: To
      determine the association between duration of infant breastfeeding and
      intelligence in young adulthood. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      longitudinal birth cohort study conducted in a sample of 973 men and women and a
      sample of 2280 men, all of whom were born in Copenhagen, Denmark, between October
      1959 and December 1961. The samples were divided into 5 categories based on
      duration of breastfeeding, as assessed by physician interview with mothers at a 1
      year examination. MAIN OUTCOME MEASURES: Intelligence, assessed using the
      Wechsler Adult Intelligence Scale (WAIS) at a mean age of 27.2 years in the mixed
      sex sample and the Borge Priens Prove (BPP) test at a mean age of 18.7 years in
      the all-male sample. Thirteen potential confounders were included as covariates:
      parental social status and education; single mother status; mother's height, age,
      and weight gain during pregnancy and cigarette consumption during the third
      trimester; number of pregnancies; estimated gestational age; birth weight; birth
      length; and indexes of pregnancy and delivery complications. RESULTS: Duration of
      breastfeeding was associated with significantly higher scores on the Verbal,
      Performance, and Full Scale WAIS IQs. With regression adjustment for potential
      confounding factors, the mean Full Scale WAIS IQs were 99.4, 101.7, 102.3, 106.0,
      and 104.0 for breastfeeding durations of less than 1 month, 2 to 3 months, 4 to 6
      months, 7 to 9 months, and more than 9 months, respectively (P =.003 for overall
      F test). The corresponding mean scores on the BPP were 38.0, 39.2, 39.9, 40.1,
      and 40.1 (P =.01 for overall F test). CONCLUSION: Independent of a wide range of
      possible confounding factors, a significant positive association between duration
      of breastfeeding and intelligence was observed in 2 independent samples of young
      adults, assessed with 2 different intelligence tests.

PMID- 11988058
TI  - Benefits and costs of using HPV testing to screen for cervical cancer.
AB  - CONTEXT: Despite quality assurance standards, Papanicolaou (Pap) test
      characteristics remain less than optimal. OBJECTIVE: To compare the societal
      costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their
      combination to screen for cervical cancer. DESIGN, SETTING, AND POPULATION: A
      simulation model of neoplasia natural history was used to estimate the societal
      costs and quality-adjusted life expectancy associated with 18 different general
      population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV
      testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US
      women beginning at age 20 years and continuing to 65 years, 75 years, or death.
      MAIN OUTCOME MEASURE: Discounted costs per quality-adjusted life-year (QALY)
      saved of each screening strategy. RESULTS: Maximal savings in lives were achieved
      by screening every 2 years until death with combined HPV and Pap testing at an
      incremental cost of $76 183 per QALY compared with Pap testing alone every 2
      years. Stopping biennial screening with HPV and Pap testing at age 75 years
      captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per
      QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the
      benefits achievable by continuing to screen until age 75 years. Human
      papillomavirus screening alone was equally effective as Pap testing alone at any
      given screening interval or age of screening cessation but was more costly and
      therefore was dominated. In sensitivity analyses, HPV testing would be more
      effective and less costly than Pap testing at a cost threshold of $5 for an HPV
      test. CONCLUSIONS: Screening with HPV plus Pap tests every 2 years appears to
      save additional years of life at reasonable costs compared with Pap testing
      alone. Applying age limits to screening is a viable option to maintain benefits
      while reducing costs.

PMID- 11988059
TI  - Cost-effectiveness of alternative triage strategies for atypical squamous cells
      of undetermined significance.
AB  - CONTEXT: Every year approximately 2 million US women are diagnosed as having a
      cervical cytological result of atypical squamous cells of undetermined
      significance (ASC-US). OBJECTIVE: To determine the most efficient and cost
      effective management strategy for women in the United States diagnosed as having
      ASC-US. DESIGN AND SETTING: Cost-effectiveness analysis of data from clinical
      trials, prospective studies, and other published literature. A computer-based
      model was used to compare 4 management strategies for a cytological result of ASC
      US: immediate colposcopy; human papillomavirus (HPV) triage, which includes
      colposcopy if high-risk HPV types are detected; repeat cytology, which includes
      follow-up cytology at 6 and 12 months and referral for colposcopy if a repeat
      abnormal result occurs; and reclassifying ASC-US as normal in which a cytological
      result of ASC-US is ignored. Reflex HPV DNA testing uses either residual liquid
      based cytological specimens or samples co-collected at the time of the initial
      screening for conventional cytology. Another method, referred to as the 2-visit
      HPV DNA triage, requires a woman with an ASC-US result to return within 1 month
      to provide another speciman sample. MAIN OUTCOME MEASURES: Years of life saved
      (YLS), quality-adjusted life-years (QALYs), and incremental cost-effectiveness
      ratios. RESULTS: The least costly strategy for biennial screening was to
      reclassify ASC-US as normal, resulting in a reduction in total cancer incidence
      of 75% for conventional cytology and 84% for liquid-based cytology compared with
      no screening. The next least costly strategy was HPV DNA testing resulting in a
      reduction in total cancer incidence of 86% for conventional cytology and 90% for
      liquid-based cytology, followed by immediate colposcopy with a reduction of 87%
      and 91%, respectively. Compared with reflex HPV DNA testing, a strategy of repeat
      cervical cytology or delayed HPV testing costs more but is less effective. When
      all strategies were compared simultaneously, varying frequency and type of
      cytological test, biennial (vs every 3 years) liquid-based cytology with reflex
      HPV testing had a cost of $174 200 per YLS. In a similar comparison, liquid-based
      cytology with reflex HPV testing conducted every 3 years (vs every 5 years) had a
      cost of $59 600 per YLS and was more effective and less costly than a strategy of
      conventional cytology incorporating repeat cytology or immediate colposcopy
      conducted biennially. CONCLUSION: Reflex HPV DNA testing provides the same or
      greater life expectancy benefits and is more cost-effective than other management
      strategies for women diagnosed as having ASC-US.

PMID- 11988060
TI  - Hemorrhagic fever viruses as biological weapons: medical and public health
      management.
AB  - OBJECTIVE: To develop consensus-based recommendations for measures to be taken by
      medical and public health professionals if hemorrhagic fever viruses (HFVs) are
      used as biological weapons against a civilian population. PARTICIPANTS: The
      Working Group on Civilian Biodefense included 26 representatives from academic
      medical centers, public health, military services, governmental agencies, and
      other emergency management institutions. EVIDENCE: MEDLINE was searched from
      January 1966 to January 2002. Retrieved references, relevant material published
      prior to 1966, and additional sources identified by participants were reviewed.
      CONSENSUS PROCESS: Three formal drafts of the statement that synthesized
      information obtained in the evidence-gathering process were reviewed by the
      working group. Each draft incorporated comments and judgments of the members. All
      members approved the final draft. CONCLUSIONS: Weapons disseminating a number of
      HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days
      later, associated with clinical manifestations that could include rash,
      hemorrhagic diathesis, and shock. The mode of transmission and clinical course
      would vary depending on the specific pathogen. Diagnosis may be delayed given
      clinicians' unfamiliarity with these diseases, heterogeneous clinical
      presentation within an infected cohort, and lack of widely available diagnostic
      tests. Initiation of ribavirin therapy in the early phases of illness may be
      useful in treatment of some of these viruses, although extensive experience is
      lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

PMID- 11988061
TI  - Needlestick transmission of hepatitis C.
AB  - Hepatitis C virus (HCV) transmission following a needlestick is an important
      threat to health care workers. We present the case of a 29-year-old medical
      intern who sustained a needlestick injury from a source patient known to be
      infected with both human immunodeficiency virus and HCV. The case patient
      subsequently developed acute HCV infection. The optimal strategy for diagnosing
      HCV infection after occupational exposures has not been defined. At a minimum,
      HCV antibody and alanine aminotransferase testing should be done within several
      days of exposure (to assess if the health care worker is already infected with
      HCV) and 6 months after percutaneous, mucosal, or nonintact skin exposure to
      blood or infectious body fluids from an HCV-infected patient. Currently, it is
      not possible to prevent HCV infection after exposure. However, recent data
      suggest that early treatment of acute HCV infection with interferon alpha may be
      highly effective in preventing chronic HCV infection. These data underscore the
      importance of identifying persons with acute HCV infection and promptly referring
      them to experienced clinicians who can provide updated counseling and treatment.

PMID- 11988062
TI  - The glycemic index: physiological mechanisms relating to obesity, diabetes, and
      cardiovascular disease.
AB  - The glycemic index was proposed in 1981 as an alternative system for classifying
      carbohydrate-containing food. Since then, several hundred scientific articles and
      numerous popular diet books have been published on the topic. However, the
      clinical significance of the glycemic index remains the subject of debate. The
      purpose of this review is to examine the physiological effects of the glycemic
      index and the relevance of these effects in preventing and treating obesity,
      diabetes, and cardiovascular disease.

PMID- 11988063
TI  - Careers in translational clinical research-historical perspectives, future
      challenges.

PMID- 11988064
TI  - Visualizing cost-effectiveness analysis.

PMID- 11988069
TI  - Characterization of an activated mutant of focal adhesion kinase: 'SuperFAK'.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an
      important role in normal cellular processes such as adhesion, spreading,
      migration, proliferation and survival. In addition, FAK is overexpressed in a
      variety of cancer cells and tumours and may play a role in the development of
      human cancer. As a prelude to modelling the role of aberrant FAK signalling in
      the initiation of cancer, the goal of the present study was to engineer point
      mutations in FAK that would enhance enzymic activity. A number of substitutions
      that were reported as activating mutations in other tyrosine kinases were
      introduced into FAK. Glutamic acid substitutions for two lysine residues in the
      activation loop of FAK, based upon the K650E (Lys(650-->)Glu) mutant of
      fibroblast-growth-factor receptor 3, were made to create 'SuperFAK'. Two brain
      specific exons were engineered into avian FAK to create FAK6.7. SuperFAK and, to
      a lesser extent, FAK6.7, exhibited increased catalytic activity in vitro compared
      with wild-type FAK. The expression of SuperFAK and FAK6.7 in fibroblasts led to
      hyperphosphorylation of FAK substrates. Although the catalytic activity of
      SuperFAK and FAK6.7 was largely independent of cell adhesion, tyrosine
      phosphorylation of downstream substrates was adhesion-dependent. Further, since
      SuperFAK exhibited the same ability as wild-type FAK to recruit Src family
      kinases, tyrosine phosphorylation of substrates was likely due to direct
      phosphorylation by FAK. In addition to enhanced biochemical signalling, SuperFAK
      also increased the motility of epithelial cells. SuperFAK and FAK6.7 may be
      valuable molecular tools to investigate the potential role of aberrant FAK
      signalling in human disease.

PMID- 11988070
TI  - Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic
      assay with derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and
      application to Nepsilon-carboxymethyl-lysine- and Nepsilon-(1-carboxyethyl)lysine
      modified albumin.
AB  - Glycation of proteins leads to the formation of early glycation adducts
      (fructosamine derivatives) and advanced glycation endproducts (AGEs). Formation
      of AGEs has been linked to the development of cataract, diabetic complications,
      uraemia, Alzheimer's disease and other disorders. AGEs are a group of compounds
      of diverse molecular structure and biological function. To characterize AGE
      modified proteins used in studies of structural and functional effects of
      glycation, an assay was developed that surveys the content of early and advanced
      glycation adducts in proteins. The assay procedure involved enzymic hydrolysis of
      protein substrate, derivatization of the hydrolysate with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate (AQC) and HPLC of the resulting adducts with
      fluorimetric detection. Structural isomers of methylglyoxal-derived
      hydroimidazolone, glyoxal-derived hydroimidazolone, 3-deoxyglucosone-derived
      hydroimidazolone and N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6
      tetrahydropyrimidin-2-yl)-ornithine (THP) were determined for the first time.
      AGEs with intrinsic fluorescence (argpyrimidine, pentosidine) were assayed
      without derivatization. Limits of detection were 2-17 pmol and levels of recovery
      were 50-99%, depending on the analyte. The AQC assay resolved structural and
      epimeric isomers of methylglyoxal-derived hydroimidazolones and THP.
      Hydroimidazolones, THP and argpyrimidine were AGEs of short-to-intermediate
      stability under physiological conditions, with half-lives of 1-2 weeks. Their
      measurement provides further insight into the glycation process. The assay was
      applied to the characterization of human serum albumin minimally and highly
      modified by N(epsilon)-carboxymethyl-lysine and N(epsilon)-(1-carboxyethyl)
      lysine.

PMID- 11988071
TI  - Chromatographic assay of glycation adducts in human serum albumin glycated in
      vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and
      intrinsic fluorescence.
AB  - Glycation of proteins leads to the formation of advanced glycation endproducts
      (AGEs) of diverse molecular structure and biological function. Serum albumin
      derivatives modified to minimal and high extents by methylglyoxal and glucose in
      vitro have been used in many studies as model AGE proteins. The early and
      advanced glycation adduct contents of these proteins were investigated using the
      6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of
      enzymic hydrolysates. AGEs derived from methylglyoxal, glyoxal and 3
      deoxyglucosone, the hydroimidazolones N(delta)-(5-hydro-5-methyl-4-imidazolon-2
      yl)-ornithine (MG-H1), N(delta)-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) and
      N(delta)-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine (3DG-H1),
      bis(lysyl)imidazolium cross-links methylglyoxal-derived lysine dimer (MOLD),
      glyoxal-derived lysine dimer (GOLD), 3-deoxyglucosone-derived lysine dimer
      (DOLD), monolysyl adducts N(epsilon)-(1-carboxyethyl)lysine (CEL), N(epsilon)
      carboxymethyl-lysine (CML) and pyrraline, other AGEs, N(delta)-(4-carboxy-4,6
      dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)ornithine (THP),
      argpyrimidine and pentosidine, and fructosyl-lysine were determined. AGEs with
      intrinsic fluorescence (argpyrimidine and pentosidine) were assayed without
      derivatization. Human serum albumin (HSA) glycated minimally by methylglyoxal in
      vitro contained mainly MG-H1 with minor amounts of THP and argpyrimidine. Similar
      AGEs were found in prothrombin glycated minimally by methylglyoxal and in
      N(alpha)-t-butyloxycarbonyl-arginine incubated with methylglyoxal. HSA glycated
      highly by methylglyoxal contained mainly argpyrimidine, MG-H1 and THP, with minor
      amounts of CEL and MOLD. HSA glycated minimally by glucose in vitro contained
      mainly fructosyl-lysine and CML, with minor amounts of THP, MG-H1, G-H1, 3DG-H1,
      argpyrimidine and DOLD. HSA glycated highly by glucose contained these AGEs and
      pyrraline, and very high amounts ( approximately 8 mol/mol of protein) of
      fructosyl-lysine. Most AGEs in albumin glycated minimally by methylglyoxal and
      glucose were identified. Significant proportions of arginine and lysine-derived
      AGEs in albumin modified highly by methylglyoxal, and lysine-derived AGEs in
      albumin modified highly by glucose, remain to be identified.

PMID- 11988072
TI  - Characteristics of physiological inducers of the ethanol utilization (alc)
      pathway in Aspergillus nidulans.
AB  - The ethanol utilization (alc) pathway in Aspergillus nidulans is one of the
      strongest expressed gene systems in filamentous fungi. The pathway-specific
      activator AlcR requires the presence of an inducing compound to activate
      transcription of genes under its control. We have demonstrated recently that
      acetaldehyde is the sole physiological inducer of ethanol catabolism. In the
      present study we show that compounds with catabolism related to that of ethanol,
      i.e. primary alcohols, primary monoamines and l-threonine, act as inducers
      because their breakdown results in the production of inducing aliphatic
      aldehydes. Such aldehydes were shown to induce the alc genes efficiently at low
      external concentrations. When ethanol is mixed with representatives of another
      class of strong direct inducers, ketones, the physiological inducer,
      acetaldehyde, prevails as effector. Although direct inducers essentially carry a
      carbonyl function, not all aldehydes and ketones act as inducers. Structural
      features discriminating non-inducing from inducing compounds concern: (i) the
      length of the aliphatic side group(s); (ii) the presence and nature of any non
      aliphatic substituent. These characteristics enable us to predict whether or not
      a given carbonyl compound will induce the alc genes.

PMID- 11988073
TI  - Somatostatin-induced paradoxical increase in intracellular Ca2+ concentration and
      insulin release in the presence of arginine vasopressin in clonal HIT-T15 beta
      cells.
AB  - Somatostatin, a hormone that signals via G(i)/G(o), usually inhibits increases in
      intracellular calcium concentration ([Ca(2+)](i)) and insulin release from beta
      cells. We have found that in the presence of arginine vasopressin (AVP), which
      signals via G(q), somatostatin increased [Ca(2+)](i), leading to insulin release
      in HIT-T15 cells. The increase in [Ca(2+)](i) by somatostatin was observed even
      after 60 min of AVP treatment. Somatostatin alone failed to increase [Ca(2+)](i)
      and insulin release. Somatostatin induced changes in [Ca(2+)](i) in a biphasic
      pattern, characterized by a sharp and transient increase followed by a rapid
      decline to sub-basal levels. Pretreatment with pertussis toxin, which inactivates
      G(i)/G(o), abolished the effects of somatostatin. U-73122, an inhibitor of
      phospholipase C, antagonized the somatostatin-induced increase in [Ca(2+)](i). In
      Ca(2+)-free medium, somatostatin still increased [Ca(2+)](i). Depletion of
      intracellular Ca(2+) stores with thapsigargin, a microsomal Ca(2+)-ATPase
      inhibitor, abolished somatostatin's effect. In the presence of bradykinin,
      another G(q)-coupled receptor agonist, somatostatin also increased [Ca(2+)](i),
      but not in the presence of isoproterenol (a G(s)-coupled receptor agonist) or
      medetomidine (a G(i)/G(o)-coupled receptor agonist). Our findings suggest that
      somatostatin signals through G(i)/G(o), and involves phospholipase C and Ca(2+)
      release from the endoplasmic reticulum. The increase in [Ca(2+)](i) by
      somatostatin leads to insulin release. This cross-talk is specific to G(q) and
      G(i)/G(o), and is not limited to the AVP and somatostatin receptors.

PMID- 11988074
TI  - Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces
      apoptosis and caspase-dependent degradation of haematopoietic lineage cell
      specific protein 1 (HS1) in Jurkat cells.
AB  - Incubation of Jurkat cells with 4,5,6,7-tetrabromobenzotriazole (TBB), a specific
      inhibitor of protein kinase CK2, induces dose-and time-dependent apoptosis as
      judged by several criteria. TBB-promoted apoptosis is preceded by inhibition of
      Ser/Thr phosphorylation of haematopoietic lineage cell-specific protein 1 (HS1)
      and is accompanied by caspase-dependent fragmentation of the same protein. Both
      effects are also observable if apoptosis is promoted by anti-Fas antibodies and
      by etoposide. Moreover, in vitro experiments show that HS1, once phosphorylated
      by CK2, becomes refractory to cleavage by caspase-3. These findings, in
      conjunction with similar data in the literature concerning two other CK2 protein
      substrates, Bid and Max, suggest that CK2 may play a general anti-apoptotic role
      through the generation of phosphorylated sites conferring resistance to caspase
      cleavage.

PMID- 11988075
TI  - The same rat Delta6-desaturase not only acts on 18- but also on 24-carbon fatty
      acids in very-long-chain polyunsaturated fatty acid biosynthesis.
AB  - The recently cloned Delta6-desaturase is known to catalyse the first step in very
      long-chain polyunsaturated fatty acid biosynthesis, i.e. the desaturation of
      linoleic and alpha-linolenic acids. The hypothesis that this enzyme could also
      catalyse the terminal desaturation step, i.e. the desaturation of 24-carbon
      highly unsaturated fatty acids, has never been elucidated. To test this
      hypothesis, the activity of rat Delta6-desaturase expressed in COS-7 cells was
      investigated. Recombinant Delta6-desaturase expression was analysed by Western
      blot, revealing a single band at 45 kDa. The putative involvement of this enzyme
      in the Delta6-desaturation of C(24:5) n-3 to C(24:6) n-3 was measured by
      incubating transfected cells with C(22:5) n-3. Whereas both transfected and non
      transfected COS-7 cells were able to synthesize C(24:5) n-3 by elongation of
      C(22:5) n-3, only cells expressing Delta6-desaturase were also able to produce
      C(24:6) n-3. In addition, Delta6-desaturation of [1-(14)C]C(24:5) n-3 was assayed
      in vitro in homogenates from COS-7 cells expressing Delta6-desaturase or not,
      showing that Delta6-desaturase catalyses the conversion of C(24:5) n-3 to C(24:6)
      n-3. Evidence is therefore presented that the same rat Delta6-desaturase
      catalyses not only the conversion of C(18:3) n-3 to C(18:4) n-3, but also the
      conversion of C(24:5) n-3 to C(24:6) n-3. A similar mechanism in the n-6 series
      is strongly suggested.

PMID- 11988076
TI  - mu-1,2-Peroxobridged di-iron(III) dimer formation in human H-chain ferritin.
AB  - Biomineralization of the ferritin iron core involves a complex series of events
      in which H(2)O(2) is produced during iron oxidation by O(2) at a dinuclear
      centre, the 'ferroxidase site', located on the H-subunit of mammalian proteins.
      Rapid-freeze quench Mossbauer spectroscopy was used to probe the early events of
      iron oxidation and mineralization in recombinant human ferritin containing 24 H
      subunits. The spectra reveal that a mu-1,2-peroxodiFe(III) intermediate (species
      P) with Mossbauer parameters delta (isomer shift)=0.58 mm/s and DeltaE(Q)
      (quadrupole splitting)=1.07 mm/s at 4.2 K is formed within 50 ms of mixing Fe(II)
      with the apoprotein. This intermediate accounts for almost all of the iron in the
      sample at 160 ms. It subsequently decays within 10 s to form a mu-oxodiFe(III)
      protein complex (species D), which partially vacates the ferroxidase sites of the
      protein to generate Fe(III) clusters (species C) at a reaction time of 10 min.
      The intermediate peroxodiFe(III) complex does not decay under O(2)-limiting
      conditions, an observation suggesting inhibition of decay by unreacted Fe(II), or
      a possible role for O(2) in ferritin biomineralization in addition to that of
      direct oxidation of iron(II).

PMID- 11988077
TI  - Primary arrest of circulating platelets on collagen involves phosphorylation of
      Syk, cortactin and focal adhesion kinase: studies under flow conditions.
AB  - After a vessel wall injury, platelets adhere to the subendothelium following a
      sequence of events: arrest of single platelets on the surface, progression to
      platelet spreading and final aggregation. Primary arrest of circulating platelets
      on subendothelial components occurs through platelet glycoprotein (GP) Ib and
      collagen receptors; then platelets spread and aggregate through a GPIIb-IIIa
      dependent mechanism. A series of strategies were applied to analyse the tyrosine
      phosphorylation mechanisms occurring at the different stages of platelet adhesion
      on subendothelial components under flow conditions, with special attention to
      primary arrest. To evaluate spread platelets, samples were exposed to
      acetylsalicylic acid, which blocks aggregate formation. To study single platelets
      in contact, a monoclonal antibody specific for GPIIb-IIIa was used to prevent
      platelet spreading and further aggregation. This experimental situation was also
      investigated using blood from two patients with Glanzmann's thrombasthenia (i.e.
      lacking GPIIb-IIIa). Results demonstrated that blockade of both spreading and
      aggregation results in significant changes in the tyrosine-phosphorylation
      patterns. Arrest of single platelets on collagen-rich surfaces resulted in
      phosphorylation of p125, identified as focal adhesion kinase (FAK), the 80/85 kDa
      doublet (cortactin), and p72, identified as Syk. Arrest of single platelets on
      von Willebrand factor as adhesive substrate showed that interaction through GPIb
      induces Syk phosphorylation, but not that of cortactin and FAK. Our data indicate
      that the initial arrest of platelets on subendothelial components involves Syk
      phosphorylation, which seems to be GPIb-dependent, and this is followed by
      activation and phosphorylation of cortactin and FAK. These processes seem to
      occur before GPIIb-IIIa becomes activated.

PMID- 11988078
TI  - A novel pathway for adrenergic stimulation of cAMP-response-element-binding
      protein (CREB) phosphorylation: mediation via alpha1-adrenoceptors and protein
      kinase C activation.
AB  - Because of the central role of adrenergic mechanisms in the expression of crucial
      genes during brown adipocyte differentiation, we examined the activation
      (phosphorylation) of CREB (cAMP-response-element-binding protein) in mouse brown
      adipocytes in primary culture. We found that noradrenaline ('norepinephrine')
      stimulated CREB phosphorylation rapidly (maximum effect in < or =5 min with slow
      decay) and efficiently (EC(50), 6 nM). The increase in CREB phosphorylation
      coincided with increased expression of an artificial cAMP-response-element
      containing reporter construct. CREB phosphorylation was partly inhibitable, both
      by the beta-adrenergic antagonist propranolol and by the alpha(1)-adrenergic
      antagonist prazosin. Adenylate cyclase hyperactivation (by forskolin) could
      stimulate CREB phosphorylation to the same extent as noradrenaline. The alpha(1)
      adrenergic agonist cirazoline also increased CREB phosphorylation. An increase in
      intracellular [Ca(2+)] had, however, no effect, but protein kinase C activation
      by PMA was a potent stimulator. The cirazoline-stimulated (alpha(1)-adrenergic)
      CREB phosphorylation was inhibited by a desensitizing pretreatment with PMA,
      demonstrating that the alpha(1)-stimulation was mediated via protein kinase C
      activation; neither Src nor extracellular-signal-regulated kinases 1 and 2
      activation was involved in the signalling process. We conclude that CREB
      phosphorylation in brown adipocytes is mediated not only through the classical
      beta-adrenergic/cAMP pathway but also through a novel alpha(1)-adrenergic/protein
      kinase C/CREB pathway, which has not been described previously in any tissue.

PMID- 11988079
TI  - Isolation and characterization of a polymerized prion protein.
AB  - A polymerized form of recombinant mouse prion protein (mPrP) domain 23-231 [mPrP
      (23-231)], designated mPrP-z, was generated at acidic pH (pH 2-5) in the presence
      of selected concentrations of denaturant (2 M guanidinium chloride or 5 M urea).
      This isoform of mPrP is stable in acidic solution after removal of denaturant. It
      can be isolated and purified using reversed-phase HPLC or size-exclusion HPLC.
      mPrP-z bears structural properties that partially resemble those of scrapie
      prion. Unlike the native mPrP-(23-231) (mPrP-N), mPrP-z exhibits a high content
      of beta-sheet structure, as shown by CD spectroscopy, and exists as an oligomer
      with an approximate molecular mass of 340000 Da, as measured by light scattering.
      However, similarly to mPrP-N, mPrP-z contains the intact disulphide bond and is
      sensitive to digestion by proteinase K.

PMID- 11988080
TI  - Identification of an initiator-like element essential for the expression of the
      tissue inhibitor of metalloproteinases-4 (Timp-4) gene.
AB  - We have used real-time quantitative reverse transcriptase PCR (TaqMan) to
      quantify the expression of the four tissue inhibitor of metalloproteinases (Timp)
      genes in mouse tissues during development and in the adult. Among the four Timp
      genes, Timp-4 shows the most restricted pattern of expression, with highest RNA
      levels in brain, heart and testes. These data indicate that in the brain, Timp-4
      transcripts are temporally regulated during development, becoming more abundant
      than those of the other Timps after birth. Cloning of the Timp-4 gene confirmed a
      five-exon organization resembling that of Timp-2 and Timp-3, and like all Timps,
      Timp-4 is located within an intron of a synapsin gene. Ribonuclease protection
      analysis and 5'-rapid amplification of cDNA ends PCR identified multiple
      transcription starts for Timp-4 from brain and heart mRNA. The promoter region of
      Timp-4 was functional in transient transfection analysis in mouse C3H10T1/2
      fibroblasts, where it directed basal expression that was non-inducible by serum.
      The TATA-less promoter contains consensus motifs for Sp1 and an inverted CCAAT
      box upstream of an initiator-like element that is in close proximity to a
      transcription start site. Mutation of the CCAAT box caused a 2-fold increase in
      reporter expression. More significantly, mutation of the Sp1 motif or initiator
      like element almost completely abolished reporter expression. This first
      functional characterization of the Timp-4 promoter shows it to be distinct from
      other members of the Timp family and provides insights into potential mechanisms
      controlling the tight spatio-temporal expression pattern of the gene.

PMID- 11988081
TI  - L-Lactate transport into rat heart mitochondria and reconstruction of the L
      lactate/pyruvate shuttle.
AB  - In vitro reconstruction of the L-lactate/pyruvate shuttle has been performed,
      which allows NADH oxidation outside rat heart mitochondria. Such a shuttle occurs
      due to the combined action of the novel mitochondrial L-lactate/pyruvate
      antiporter, which differs from the monocarboxylate carrier, and the mitochondrial
      L-lactate dehydrogenase. The rate of L-lactate/pyruvate antiport proved to
      regulate the shuttle in vitro.

PMID- 11988082
TI  - Constitutive expression of hZnT4 zinc transporter in human breast epithelial
      cells.
AB  - Zinc is an essential trace element required by all living organisms. An adequate
      supply of zinc is particularly important in the neonatal period. Zinc is a
      significant component of breast milk, which is transported across the maternal
      epithelia during lactation. The mechanisms by which zinc becomes a constituent of
      breast milk have not been elucidated. The function of the zinc transporter ZnT4
      in the transport of zinc into milk during lactation was previously demonstrated
      by studies of a mouse mutant, the 'lethal milk' mouse, where a mutation in the
      ZnT4 gene decreased the transport of zinc into milk. In the present study, we
      have investigated the expression of the human orthologue of ZnT4 (hZnT4) in the
      human breast. We detected hZnT4 mRNA expression in the tissue from the resting
      and lactating human breast, using reverse-transcriptase PCR. Western-blot
      analysis using antibodies to peptide sequences of hZnT4 detected a major band of
      the predicted size of 47 kDa and a minor band of 77 kDa, in extracts from the
      resting and lactating breast tissues. There was no difference in the hZnT4
      expression levels between lactating and resting breasts. The hZnT4 protein was
      present in the luminal cells of the ducts and alveoli where it had a granular
      distribution. A cultured human breast epithelial cell line PMC42 was used to
      investigate the subcellular distribution of hZnT4 and this showed a granular
      label throughout the cytoplasm, consistent with a vesicular localization. The
      presence of zinc-containing intracellular vesicles was demonstrated by using the
      zinc-specific fluorphore Zinquin (ethyl-[2-methyl-8-p-toluenesulphonamido-6
      quinolyloxy]acetate). Double labelling indicated that there was no obvious
      overlap between Zinquin and the hZnT4 protein, suggesting that hZnT4 was not
      directly involved in the transport of zinc into vesicles. We detected expression
      of two other members of the hZnT family, hZnT1 and hZnT3, in human breast
      epithelial cells. We conclude that hZnT4 is constitutively expressed in the human
      breast and may be one of the several members of the ZnT family involved in the
      transport of zinc into milk.

PMID- 11988083
TI  - Elevation of hepatic sulphotransferase activities in mice with resistance to
      cystic fibrosis.
AB  - The severity of intestinal disease in the cystic fibrosis (CF) transmembrane
      conductance regulator (CFTR) (-/-) mice has been reported to co-segregate with
      gene loci which contain the genes for hydroxysteroid sulphotransferase (SULT).
      Because of the potential involvement of steroid hormones in CF, we investigated
      levels of steroid SULT activity in the livers of CFTR mice to determine whether
      the levels of SULT activity correlate with the occurrence or severity of CF. To
      elucidate the possible role of SULT activity in ameliorating the deleterious
      effects of CF in CFTR (-/-) mice, we determined the levels of phenol SULT (PST),
      hydroxysteroid SULT [dehydroepiandrosterone (DHEA)-ST] and oestrogen SULT (EST)
      activity in control CFTR (+/+), heterozygous CFTR (+/-) and homozygous CFTR (-/-)
      mice, which survive to adulthood. The level of PST activity was not significantly
      different between any of the groups of mice, regardless of sex or genotype.
      Although DHEA-ST activity was significantly higher in female mice than in male
      mice, there was no difference in DHEA-ST activity that could be correlated with
      genotype. In contrast with PST and DHEA-ST activities, we found that some male
      and all female adult CFTR (-/-) mice had elevated, dramatically different levels
      of EST from both CFTR (+/+) and CFTR (+/-) mice. Results from these SULT activity
      experiments were confirmed by Northern-blot analysis of mouse-liver RNA.
      Subsequent studies with preweanling mice revealed no differences in the levels of
      EST that could be correlated with genotype. Thus this study indicates that EST is
      elevated significantly in CFTR (-/-) mice which survive to adulthood and provides
      important biochemical information that EST levels may be protective in CF.

PMID- 11988084
TI  - Plant-derived phenolic compounds prevent the DNA single-strand breakage and
      cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism.
AB  - The protective effects of selected members from a series of caffeic acid esters
      and flavonoids were tested in various toxicity paradigms using U937 cells,
      previously shown to be sensitive to either iron chelators or bona fide radical
      scavengers or to both classes of compounds. It was found that all the protective
      polyphenols were active at very low concentrations and that their effects were
      observed only under those conditions in which iron chelators also afforded
      protection. Consistently, active polyphenolic compounds, unlike the inactive
      ones, effectively chelated iron in an in vitro system. It follows that, at least
      under the experimental conditions utilized in the present study, the most
      prominent activity of these polyphenolic compounds resides in their ability to
      chelate iron. Further studies revealed that the protective effects afforded by
      the caffeic acid esters and flavonoids were largely mediated by the catechol
      moiety and that the relative biological potency of these compounds was a direct
      function of their lipophilicity.

PMID- 11988085
TI  - Isoaspartyl dipeptidase activity of plant-type asparaginases.
AB  - Recombinant plant-type asparaginases from the cyanobacteria Synechocystis sp. PCC
      (Pasteur culture collection) 6803 and Anabaena sp. PCC 7120, from Escherichia
      coli and from the plant Arabidopsis thaliana were expressed in E. coli with
      either an N-terminal or a C-terminal His tag, and purified. Although each of the
      four enzymes is encoded by a single gene, their mature forms consist of two
      protein subunits that are generated by autoproteolytic cleavage of the primary
      translation products at the Gly-Thr bond within the sequence GTI/VG. The enzymes
      not only deamidated asparagine but also hydrolysed a range of isoaspartyl
      dipeptides. As various isoaspartyl peptides are known to arise from proteolytic
      degradation of post-translationally altered proteins containing isoaspartyl
      residues, and from depolymerization of the cyanobacterial reserve polymer multi-L
      arginyl-poly-L-aspartic acid (cyanophycin), plant-type asparaginases may not only
      function in asparagine catabolism but also in the final steps of protein and
      cyanophycin degradation. The properties of these enzymes are compared with those
      of the sequence-related glycosylasparaginases.

PMID- 11988086
TI  - Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small
      soluble and membrane forms, inhibits adipocyte differentiation: role of
      alternative splicing.
AB  - We originally identified preadipocyte factor-1 (Pref-1) as an inhibitor of
      adipogenesis by the fact that constitutive expression of full-length Pref-1A
      inhibits differentiation of 3T3-L1 cells into adipocytes. Subsequently, we found
      that the membrane form of Pref-1 is proteolytically processed at two sites in the
      extracellular domain, resulting in the larger (50 kDa) and smaller (25 kDa)
      soluble forms. A specific form(s) of Pref-1, which is active in inhibiting
      adipocyte differentiation, has not been elucidated. Here, various artificial
      constructs and alternative-splicing variants of Pref-1 were stably transfected
      into 3T3-L1 cells, or conditioned media from COS cells transfected with the
      various forms were added into differentiating 3T3-L1 cells. Judging by Oil Red O
      staining for lipid accumulation and expression of adipocyte markers, we
      determined that, unlike the full-length Pref-1A and the constructed large soluble
      form, the artificial membrane form of Pref-1 lacking the processing site proximal
      to the membrane was not effective in inhibiting adipogenesis. Furthermore,
      conditioned media from COS cells transfected with the construct containing only
      the first three epidermal growth factor repeats, corresponding to the small
      soluble form, was not effective in inhibiting adipocyte differentiation. Of the
      four alternative-splicing products, Pref-1A and Pref-1B, which generate both
      large and small soluble forms, inhibited adipogenesis, whereas Pref-1C and Pref
      1D, which lack the processing site proximal to the membrane and therefore
      generate only the smaller soluble form, did not show any effect. We conclude that
      only the large soluble form, and not the transmembrane or the small soluble form,
      of Pref-1 is biologically active and that alternative splicing therefore
      determines Pref-1 function in adipocyte differentiation.

PMID- 11988087
TI  - Characterization of a murine gene encoding a developmentally regulated
      cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase.
AB  - Mitogen-activated protein kinases (MAPKs) play a vital role in cellular growth
      control, but far less is known about these signalling pathways in the context of
      embryonic development. Duration and magnitude of MAPK activation are crucial
      factors in cell fate decisions, and reflect a balance between the activities of
      upstream activators and specific MAPK phosphatases (MKPs). Here, we report the
      isolation and characterization of the murine Pyst3 gene, which encodes a
      cytosolic dual-specificity MKP. This enzyme selectively interacts with, and is
      catalytically activated by, the 'classical' extracellular signal-regulated
      kinases (ERKs) 1 and 2 and, to a lesser extent, the stress-activated MAPK
      p38alpha. These properties define the ability of this enzyme to dephosphorylate
      and inactivate ERK1/2 and p38alpha, but not JNK (c-Jun N-terminal kinase) in
      vivo. When expressed in mammalian cells, the Pyst3 protein is predominantly
      cytoplasmic. Furthermore, leptomycin B causes a complete redistribution of the
      protein to the nucleus, implicating a CRM (chromosomal region
      maintenance)1/exportin 1-dependent nuclear export signal in determining the
      subcellular localization of this enzyme. Finally, whole-mount in situ
      hybridization studies in mouse embryos reveal that the Pyst3 gene is expressed
      specifically in the placenta, developing liver and in migratory muscle cells. Our
      results suggest that this enzyme may have a critical role in regulating the
      activity of MAPK signalling during early development and organogenesis.

PMID- 11988088
TI  - Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene
      interpreted by analysis of the three-dimensional protein structure.
AB  - Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive
      disease characterized by thymine-uraciluria in homozygous deficient patients.
      Cancer patients with a partial deficiency of DPD are at risk of developing severe
      life-threatening toxicities after the administration of 5-fluorouracil. Thus,
      identification of novel disease-causing mutations is of the utmost importance to
      allow screening of patients at risk. In eight patients presenting with a complete
      DPD deficiency, a considerable variation in the clinical presentation was noted.
      Whereas motor retardation was observed in all patients, no patients presented
      with convulsive disorders. In this group of patients, nine novel mutations were
      identified including one deletion of two nucleotides [1039-1042delTG] and eight
      missense mutations. Analysis of the crystal structure of pig DPD suggested that
      five out of eight amino acid exchanges present in these patients with a complete
      DPD deficiency, Pro86Leu, Ser201Arg, Ser492Leu, Asp949Val and His978Arg,
      interfered directly or indirectly with cofactor binding or electron transport.
      Furthermore, the mutations Ile560Ser and Tyr211Cys most likely affected the
      structural integrity of the DPD protein. Only the effect of the Ile370Val and a
      previously identified Cys29Arg mutation could not be readily explained by
      analysis of the three-dimensional structure of the DPD enzyme, suggesting that at
      least the latter might be a common polymorphism. Our data demonstrate for the
      first time the possible consequences of missense mutations in the DPD gene on the
      function and stability of the DPD enzyme.

PMID- 11988089
TI  - Crystal structure of human dehydroepiandrosterone sulphotransferase in complex
      with substrate.
AB  - Dehydroepiandrosterone sulphotransferase (DHEA-ST) is an enzyme that converts
      dehydroepiandrosterone (DHEA), and some other steroids, into their sulphonated
      forms. The enzyme catalyses the sulphonation of DHEA on the 3alpha-oxygen, with
      3'-phosphoadenosine-5'-phosphosulphate contributing the sulphate. The structure
      of human DHEA-ST in complex with its preferred substrate DHEA has been solved
      here to 1.99 A using molecular replacement with oestradiol sulphotransferase (37%
      sequence identity) as a model. Two alternative substrate-binding orientations
      have been identified. The primary, catalytic, orientation has the DHEA 3alpha
      oxygen and the highly conserved catalytic histidine in nearly identical positions
      as are seen for the related oestradiol sulphotransferase. The substrate, however,
      shows rotations of up to 30 degrees, and there is a corresponding rearrangement
      of the protein loops contributing to the active site. This may also reflect the
      low identity between the two enzymes. The second orientation penetrates further
      into the active site and can form a potential hydrogen bond with the
      desulphonated cofactor 3',5'-phosphoadenosine (PAP). This second site contains
      more van der Waal interactions with hydrophobic residues than the catalytic site
      and may also reflect the substrate-inhibition site. The PAP position was obtained
      from the previously solved structure of DHEA-ST co-crystallized with PAP. This
      latter structure, due to the arrangement of loops within the active site and
      monomer interactions, cannot bind substrate. The results presented here describe
      details of substrate binding to DHEA-ST and the potential relationship to
      substrate inhibition.

PMID- 11988090
TI  - Structural basis for the unusual carbohydrate-binding specificity of jacalin
      towards galactose and mannose.
AB  - Evidence is presented that the specificity of jacalin, the seed lectin from jack
      fruit (Artocarpus integrifolia), is not directed exclusively against the T
      antigen disaccharide Galbeta1,3GalNAc, lactose and galactose, but also against
      mannose and oligomannosides. Biochemical analyses based on surface-plasmon
      resonance measurements, combined with the X-ray-crystallographic determination of
      the structure of a jacalin-alpha-methyl-mannose complex at 2 A resolution,
      demonstrated clearly that jacalin is fully capable of binding mannose. Besides
      mannose, jacalin also interacts readily with glucose, N-acetylneuraminic acid and
      N-acetylmuramic acid. Structural analyses demonstrated that the relatively large
      size of the carbohydrate-binding site enables jacalin to accommodate
      monosaccharides with different hydroxyl conformations and provided unambiguous
      evidence that the beta-prism structure of jacalin is a sufficiently flexible
      structural scaffold to confer different carbohydrate-binding specificities to a
      single lectin.

PMID- 11988091
TI  - The 45 kDa collagen-binding fragment of fibronectin induces matrix
      metalloproteinase-13 synthesis by chondrocytes and aggrecan degradation by
      aggrecanases.
AB  - Fragments of fibronectin occur naturally in vivo and are increased in the
      synovial fluid of arthritis patients. We have studied the 45 kDa fragment (Fn-f
      45), representing the N-terminal collagen-binding domain of fibronectin, for its
      ability to modulate the expression of metalloproteinases by porcine articular
      chondrocytes in vitro. We report that stimulation of cultured chondrocytes, or
      cartilage explants, with Fn-f 45 increased the levels of matrix metalloproteinase
      13 (MMP-13; collagenase-3) released into the conditioned medium in a dose
      dependent manner. Increased levels of MMP-13 were due to stimulation of MMP-13
      synthesis, rather than release of MMP-13 from accumulated matrix stores. Fn-f 45
      also stimulated the synthesis of MMP-3 (stromelysin-1) from cultured chondrocytes
      and cartilage cultures. The Fn-f 45-induced increase in MMP-3 and MMP-13
      synthesis occurred via an interleukin 1-independent mechanism, since the receptor
      antagonist of interleukin-1 was unable to block the increased synthesis. The
      gelatinases, MMP-2 and MMP-9, were not modulated by Fn-f 45 in these culture
      systems. Fn-f 45 also stimulated the release of aggrecan from cartilage explants
      into conditioned medium. Neoepitope antibodies specific for aggrecan fragments
      generated by MMPs or aggrecanases showed that the Fn-f 45-induced aggrecan loss
      was mediated by aggrecanases, and not by MMPs. Extracts of cultured cartilage
      contained elevated levels of the aggrecanase-derived ITEGE(373)-G1 domain,
      whereas levels of the matrix metalloproteinase-derived DIPEN(341)-G1 domain were
      unchanged. These studies show that Fn-f 45 can induce a catabolic phenotype in
      articular chondrocytes by up-regulating the expression of metalloproteinases
      specific for the degradation of collagen and aggrecan.

PMID- 11988092
TI  - Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size,
      glycosylation and tissue distribution.
AB  - Gastric MUC5AC and MUC6 mucins were studied using polyclonal antibodies.
      Immunohistochemistry showed MUC5AC to originate from the surface epithelium,
      whereas MUC6 was produced by the glands. Mucins from the surface epithelium or
      glands of corpus and antrum were purified using CsCl/4M guanidinium chloride
      density-gradient centrifugation. MUC5AC appeared as two distinct populations at
      1.4 and 1.3 g/ml, whereas MUC6, which was enriched in the gland tissue, appeared
      at 1.45 g/ml. Reactivity with antibodies against the Le(b) structure (where Le
      represents the Lewis antigen) followed the MUC5AC distribution, whereas
      antibodies against the Le(y) structure and reactivity with the GlcNAc-selective
      Solanum tuberosum lectin coincided with MUC6, suggesting that the two mucins are
      glycosylated differently. Rate-zonal centrifugation of whole mucins and reduced
      subunits showed that both gastric MUC5AC and MUC6 are oligomeric glycoproteins
      composed of disulphide-bond linked subunits and that oligomeric MUC5AC was
      apparently smaller than MUC6. A heterogeneous population of 'low-density' MUC5AC
      mucins, which were smaller than the 'high-density' ones both before and after
      reduction, reacted with an antibody against a variable number tandem repeat
      sequence within MUC5AC, suggesting that they represent precursor forms of this
      mucin. Following ion-exchange HPLC, both MUC5AC and MUC6 appeared as several
      distinct populations, probably corresponding to 'glycoforms' of the mucins, the
      most highly charged of which were found in the gland tissue.

PMID- 11988093
TI  - Karyopherin alpha2: a control step of glucose-sensitive gene expression in
      hepatic cells.
AB  - Glucose is required for an efficient expression of the glucose transporter GLUT2
      and other genes. We have shown previously that the intracytoplasmic loop of GLUT2
      can divert a signal, resulting in the stimulation of glucose-sensitive gene
      transcription. In the present study, by interaction with the GLUT2 loop, we have
      cloned the rat karyopherin alpha2, a receptor involved in nuclear import. The
      specificity of the binding was restricted to GLUT2, and not GLUT1 or GLUT4, and
      to karyopherin alpha2, not alpha1. When rendered irreversible by a cross-linking
      agent, this transitory interaction was detected in vivo in hepatocytes. A role
      for karyopherin alpha2 in the transcription of two glucose-sensitive genes was
      investigated by transfection of native and inactive green fluorescent protein
      karyopherin alpha2 in GLUT2-expressing hepatoma cells. The amount of inactive
      karyopherin alpha2 receptor reduced, in a dose-dependent manner, the GLUT2 and
      liver pyruvate kinase mRNA levels by competition with endogenous active receptor.
      In contrast, the overexpression of karyopherin alpha2 did not significantly
      stimulate GLUT2 and liver pyruvate kinase mRNA accumulation in green fluorescent
      protein-sorted cells. The present study suggests that, in concert with glucose
      metabolism, karyopherin alpha2 transmits a signal to the nucleus to regulate
      glucose-sensitive gene expression. The transitory tethering of karyopherin alpha2
      to GLUT2 at the plasma membrane might indicate that the receptor can load the
      cargo to be imported locally.

PMID- 11988094
TI  - Nitric oxide inhibits the shedding of the glycosylphosphatidylinositol-anchored
      dipeptidase from porcine renal proximal tubules.
AB  - NO is related to the pathological condition acute renal failure, in which we
      previously observed that the level of soluble dipeptidase in urine was decreased.
      In this study the role of NO in the shedding of the glycosylphosphatidylinositol
      (GPI)-anchored form of renal dipeptidase (RDPase) was examined. The NO donors
      sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine rapidly inhibited
      the release of RDPase from porcine kidney proximal tubules. The substrate of NO
      synthase, l-Arg, also inhibited the release of RDPase, and this effect was
      reversed by the NO synthase inhibitor N(omega)-nitro-l-arginine methyl ester.
      Western-blot analyses using antibodies raised against porcine RDPase and the
      inositol-1,2-cyclic monophosphate moiety formed on phospholipase C cleavage of
      the GPI anchor demonstrated that SNP mediated its inhibitory effect on the
      release of RDPase via a GPI-specific phospholipase C (GPI-PLC). Peroxynitrite
      scavengers (deferoxamine and superoxide dismutase) or reducing agent
      (dithiothreitol) did not affect SNP's inhibition of the release of RDPase.
      Exposure to the G-protein activator AlF(-)(4) mimicked the l-Arg effect in the
      presence of a low concentration of l-Arg, and the effect was completely reversed
      by U73122, an intracellular phosphatidylinositol-specific PLC (PI-PLC) inhibitor.
      These results suggest a signal-transduction pathway involving NO, which is
      produced by NO synthase(s) following activation of a G-protein-coupled PI-PLC,
      resulting in inhibition of the GPI-PLC that cleaves and releases RDPase.
      Therefore, this indicates a role for NO as an inhibitory regulator of the
      shedding of the GPI-anchored RDPase in acute renal failure.

PMID- 11988095
TI  - Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in
      INS1E cells: effects on cell metabolism and insulin secretion.
AB  - Lipid metabolism in the beta-cell is critical for the regulation of insulin
      secretion. Pancreatic beta-cells chronically exposed to fatty acids show higher
      carnitine palmitoyltransferase I (CPT I) protein levels, higher palmitate
      oxidation rates and an altered insulin response to glucose. We examined the
      effect of increasing CPT I levels on insulin secretion in cultured beta-cells. We
      prepared a recombinant adenovirus containing the cDNA for the rat liver isoform
      of CPT I. The overexpression of CPT I in INS1E cells caused a more than a 5-fold
      increase in the levels of CPT I protein (detected by Western blotting), a 6-fold
      increase in the CPT activity, and an increase in fatty acid oxidation at 2.5 mM
      glucose (1.7-fold) and 15 mM glucose (3.1-fold). Insulin secretion was stimulated
      in control cells by 15 mM glucose or 30 mM KCl. INS1E cells overexpressing CPT I
      showed lower insulin secretion on stimulation with 15 mM glucose (-40%; P<0.05).
      This decrease depended on CPT I activity, since the presence of etomoxir, a
      specific inhibitor of CPT I, in the preincubation medium normalized the CPT I
      activity, the fatty-acid oxidation rate and the insulin secretion in response to
      glucose. Exogenous palmitate (0.25 mM) rescued glucose-stimulated insulin
      secretion (GSIS) in CPT I-overexpressing cells, indicating that the mechanism of
      impaired GSIS was through the depletion of a critical lipid. Depolarizing the
      cells with KCl or intermediary glucose concentrations (7.5 mM) elicited similar
      insulin secretion in control cells and cells overexpressing CPT I. Glucose
      induced ATP increase, glucose metabolism and the triacylglycerol content remained
      unchanged. These results provide further evidence that CPT I activity regulates
      insulin secretion in the beta-cell. They also indicate that up-regulation of CPT
      I contributes to the loss of response to high glucose in beta-cells exposed to
      fatty acids.

PMID- 11988096
TI  - Engineering N-terminal domain of tissue inhibitor of metalloproteinase (TIMP)-3
      to be a better inhibitor against tumour necrosis factor-alpha-converting enzyme.
AB  - We previously reported that full-length tissue inhibitor of metalloproteinase-3
      (TIMP-3) and its N-terminal domain form (N-TIMP-3) displayed equal binding
      affinity for tissue necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE).
      Based on the computer graphic of TACE docked with a TIMP-3 model, we created a
      number of N-TIMP-3 mutants that showed significant improvement in TACE
      inhibition. Our strategy was to select those N-TIMP-3 residues that were believed
      to be in actual contact with the active-site pockets of TACE and mutate them to
      amino acids of a better-fitting nature. The activities of these mutants were
      examined by measuring their binding affinities (K(app)(i)) and association rates
      (k(on)) against TACE. Nearly all mutants at position Thr-2 exhibited slightly
      impaired affinity as well as association rate constants. On the other hand, some
      Ser-4 mutants displayed a remarkable increase in their binding tightness with
      TACE. In fact, the binding affinities of several mutants were less than 60 pM,
      beyond the sensitivity limits of fluorimetric assays. Further studies on cell
      based processing of pro-TNF-alpha demonstrated that wild-type N-TIMP-3 and one of
      its tight-binding mutants, Ser-4Met, were capable of inhibiting the proteolytic
      shedding of TNF-alpha. Furthermore, the Ser-4Met mutant was also significantly
      more active (P<0.05) than the wild-type N-TIMP-3 in its cellular inhibition.
      Comparison of N-TIMP-3 and full-length TIMP-3 revealed that, despite their
      identical TACE-interaction kinetics, the latter was nearly 10 times more
      efficient in the inhibition of TNF-alpha shedding, with concomitant implications
      for the importance of the TIMP-3 C-terminal domain in vivo.

PMID- 11988097
TI  - Ca2+ uptake by the endoplasmic reticulum Ca2+-ATPase in rat microvascular
      endothelial cells.
AB  - In non-excitable cells, many agonists increase the intracellular Ca(2+)
      concentration ([Ca(2+)](i)) by inducing an inositol 1,4,5-trisphosphate (IP(3))
      mediated Ca(2+) release from the intracellular stores. Ca(2+) influx from the
      extracellular medium may then sustain the Ca(2+) signal. [Ca(2+)](i) recovers its
      resting level as a consequence of Ca(2+)-removing mechanisms, i.e. plasma
      membrane Ca(2+)-ATPase (PMCA) pump, Na(+)/Ca(2+) exchanger (NCX) and sarco
      endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump. In a study performed in
      pancreatic acinar cells, evidence has been provided suggesting that, during the
      decay phase of the agonist-evoked Ca(2+) transients, the Ca(2+) concentration
      within the intracellular stores remains essentially constant [Mogami, Tepikin and
      Petersen (1998) EMBO J. 17, 435-442]. It was therefore hypothesized that, in such
      a situation, intracellular Ca(2+) is not only picked up by the SERCA pump, but is
      also newly released through IP(3)-sensitive Ca(2+) channels, with the balance
      between these two processes being approximately null. The main aim of the present
      work was to test this hypothesis by a different experimental approach. Using
      cardiac microvascular endothelial cells, we found that inhibition of the SERCA
      pump has no effect on the time course of agonist-evoked Ca(2+) transients. This
      result was not due to a low capacity of the SERCA pump since, after agonist
      removal, this pump proved to be very powerful in clearing the excess of
      intracellular Ca(2+). We showed further that: (i) in order to avoid a rapid
      removal of Ca(2+) by the SERCA pump, continuous IP(3) production appears to be
      required throughout all of the decay phase of the Ca(2+) transient; and (ii)
      Ca(2+) picked up by the SERCA pump can be fully and immediately released by
      agonist application. All these results support the model of Mogami, Tepikin and
      Petersen [(1998) EMBO J. 17, 435-442]. Since the SERCA pump did not appear to be
      involved in shaping the decay phase of the agonist-evoked Ca(2+) transient, we
      inhibited the PMCA pump with carboxyeosin, and NCX with benzamil and by removing
      extracellular Na(+). The results indicate that, during the decay phase of the
      agonist-evoked Ca(2+) transient, the intracellular Ca(2+) is removed by both the
      PMCA pump and NCX. Finally, we provide evidence indicating that mitochondria have
      no role in clearing intracellular Ca(2+) during agonist-evoked Ca(2+) transients.

PMID- 11988098
TI  - Diacylglycerol activates the influx of extracellular cations in T-lymphocytes
      independently of intracellular calcium-store depletion and possibly involving
      endogenous TRP6 gene products.
AB  - In Jurkat and human peripheral blood T-lymphocytes, 1-oleoyl-2-acetyl-sn-glycerol
      (OAG), a membrane-permeant analogue of diacylglycerol, activated the influx of
      Ca(2+), Ba(2+) and Sr(2+). OAG also caused plasma-membrane depolarization in
      Ca(2+)-free media that was recovered by the addition of bivalent cation,
      indicating the activation of Na(+) influx. OAG-induced cation influx was (i)
      mimicked by the natural dacylglycerol 1-stearoyl-2-arachidonyl-sn-glycerol, (ii)
      not blocked by inhibiting protein kinase C or in the absence of phospholipase C
      activity and (iii) blocked by La(3+) and Gd(3+). Differently from OAG, both
      thapsigargin and phytohaemagglutinin activated a potent influx of Ca(2+), but
      little influx of Ba(2+) and Sr(2+). Moreover, the influx of Ca(2+) activated by
      thapsigargin and that activated by OAG were additive. Furthermore, several drugs
      (i.e. econazole, SKF96365, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 2
      aminoethoxy diphenylborate and calyculin-A), while inhibiting the influx of
      Ca(2+) induced by both thapsigargin and phytohaemagglutinin, did not affect OAG
      stimulated cation influx. Transient receptor potential (TRP) 3 and TRP6 proteins
      have been shown previously to be activated by diacylglycerol when expressed
      heterologously in animal cells [Hofmann, Obukhov, Schaefer, Harteneck, Gudermann
      and Schultz (1999) Nature (London) 397, 259-263]. In both Jurkat and peripheral
      blood T-lymphocytes, mRNA encoding TRP proteins 1, 3, 4 and 6 was detected by
      reverse transcriptase PCR, and the TRP6 protein was detected by Western blotting
      in a purified plasma-membrane fraction. We conclude that T-cells express a
      diacylglycerol-activated cation channel, unrelated to the channel involved in
      capacitative Ca(2+) entry, and associated with the expression of TRP6 protein.

PMID- 11988099
TI  - Cloning and characterization of hELD/OSA1, a novel BRG1 interacting protein.
AB  - A highly conserved multisubunit enzymic complex, SWI/SNF, participates in the
      regulation of eukaryote gene expression through its ability to remodel chromatin.
      While a single component of SWI/SNF, Swi2 or a related protein, can perform this
      function in vitro, the other components appear to modulate the activity and
      specificity of the complex in vivo. Here we describe the cloning of hELD/OSA1, a
      189 KDa human homologue of Drosophila Eld/Osa protein, a constituent of
      Drosophila SWI/SNF. By comparing conserved peptide sequences in Eld/Osa
      homologues we define three domains common to all family members. A putative DNA
      binding domain, or ARID (AT-rich DNA-interacting domain), may function in
      targetting SWI/SNF to chromatin. Two other domains unique to Eld/Osa proteins,
      EHD1 and EHD2, map to the C-terminus. We show that EHD2 mediates binding to
      Brahma-related gene 1 (BRG1), a human homologue of yeast Swi2. EHD1 and EHD2 also
      appear capable of interacting with each other. Using an antibody raised against
      EHD2 of hELD/OSA1, we detected Eld/Osa1 in endogenous SWI/SNF complexes derived
      from mouse brain.

PMID- 11988100
TI  - Characterization of a novel intracellular heparanase that has a FERM domain.
AB  - The catabolism of cell-surface heparan sulphate proteoglycans is initiated by
      endosomal heparanases, which are endoglycosidases that cleave the
      glycosaminoglycans off core proteins and degrade them to shorter
      oligosaccharides. We have purified previously four intracellular heparanase
      activities from Chinese hamster ovary (CHO) cells [Bame, Hassall, Sanderson,
      Venkatesan and Sun (1998) Biochem. J. 336, 191-200], and in the present study we
      characterize further the most abundant activity (C1A heparanase). This enzyme
      purifies as a family of 37-48 kDa proteins from both CHO cells and the rat liver,
      with the major species being 37 and 40 kDa. Amino acid sequence analysis shows
      the purified C1A heparanase protein is highly homologous with the N-terminal
      domain, or FERM domain, of the approximately 80 kDa proteins ezrin, radixin and
      moesin (ERM proteins, after ezrin-radixin-moesin). This domain, which is also
      found in erythrocyte protein 4.1, links cytoplasmic proteins to membranes.
      Antibodies against the FERM domain recognize all the C1A heparanase proteins on
      Western blots, suggesting that the smaller species are derived from a larger
      protein. Activity binds to, and is affected by, molecules known to interact with
      FERM domains, supporting the hypothesis that the intracellular C1A heparanase is
      the purified FERM domain protein. Since bacterially expressed FERM domains of
      radixin and moesin lack heparanase activity, and some tryptic peptides generated
      from the enzyme do not have a match in any ERM protein, it appears that, rather
      than being derived from ezrin, radixin or moesin, C1A heparanase may be a new
      member of the FERM domain family.

PMID- 11988101
TI  - Turnover of matrix proteins in mammalian mitochondria.
AB  - In cultured hepatocytes the turnover of several mitochondrial matrix proteins
      (e.g. acetyl-CoA acetyltransferase) appears to be initiated by CoA-mediated,
      sequential transformation into CoA-modified forms. This modification favours the
      notion that intramitochondrial degradation by a matrix-resident ATP-dependent
      protease may be preceded by a specific modification by CoA. In a mitochondrial
      matrix fraction the MgATP-dependent decrease in anti-CoA immunoreactivity
      coincided with both a decrease in the anti-protein immunoreactivity of acetyl-CoA
      acetyltransferase and/or of 3-ketoacyl-CoA thiolase, and with the appearance of
      proteolytic fragments. A closer analysis of the degradation pattern revealed,
      however, a breakdown of the unmodified acetyl-CoA acetyltransferase and of its
      CoA-modified form, A1, whereas the form that is more highly modified by CoA, A2,
      proved to be inaccessible towards an ATP-dependent protease. In mammalian
      mitochondrial matrix, proteins can be degraded selectively by a matrix-resident
      ATP-dependent protease. The process of CoA modification results finally in the
      protection of matrix proteins from degradation. In cultured hepatocytes,
      leupeptin, an inhibitor of lysosomal proteases, did not affect the steady-state
      level of the mitochondrial matrix protein acetyl-CoA acetyltransferase. However,
      leupeptin mediated a specific accumulation of mitochondrial matrix proteins in
      the cytosolic fractions of hepatocytes cultured over a 24 h period. The levels of
      acetyl-CoA acetyltransferase, 3-ketoacyl-CoA thiolase and glutamate dehydrogenase
      proteins increased 1.9-, 2.0- and 2.2-fold respectively. Their status as mature,
      oligomeric, but enzymically inactive enzymes strongly suggests that they
      originate from a leakage of autophagosomes, a constituent of the non-selective
      autophagic/lysosomal pathway for degradation of whole mitochondria.

PMID- 11988102
TI  - Use of a purified and functional recombinant calcium-channel beta4 subunit in
      surface-plasmon resonance studies.
AB  - Native high-voltage-gated calcium channels are multi-subunit complexes comprising
      a pore-forming subunit Ca(v) and at least two auxiliary subunits alpha(2)delta
      and beta. The beta subunit facilitates cell-surface expression of the channel and
      contributes significantly to its biophysical properties. In spite of its
      importance, detailed structural and functional studies are hampered by the
      limited availability of native beta subunit. Here, we report the purification of
      a recombinant calcium-channel beta(4) subunit from bacterial extracts by using a
      polyhistidine tag. The purified protein is fully functional since it binds on the
      alpha1 interaction domain, its main Ca(v)-binding site, and regulates the
      activity of P/Q calcium channel expressed in Xenopus oocytes in a similar way to
      the beta(4) subunit produced by cRNA injection. We took advantage of the
      functionality of the purified material to (i) develop an efficient surface
      plasmon resonance assay of the interaction between two calcium channel subunits
      and (ii) measure, for the first time, the affinity of the recombinant His-beta(4)
      subunit for the full-length Ca(v)2.1 channel. The availability of this purified
      material and the development of a surface-plasmon resonance assay opens two
      immediate research perspectives: (i) drug screening programmes applied to the
      Ca(v)/beta interaction and (ii) crystallographic studies of the calcium-channel
      beta(4) subunit.

PMID- 11988103
TI  - Role of the self-association of beta subunits in the oligomeric structure of
      Na+/K+-ATPase.
AB  - The two subunits of Na(+)/K(+)-ATPase that are essential for function are alpha
      and beta. Previous cross-linking studies on the oligomeric structure of the
      membrane-bound enzyme identified alpha,beta and alpha,alpha associations, but
      only the former and not the latter could be detected after solubilization. To
      study the possibility of direct beta,beta association, the purified membrane
      enzyme and a trypsin-digested enzyme that occludes cations and contains an
      essentially intact beta and fragments of alpha were subjected to oxidative cross
      linking in the presence of Cu(2+)-phenanthroline. Resolution of products on
      polyacrylamide gels, N-terminal analysis and reactivity with anti-beta antibody
      showed that, in addition to previously identified products (e.g. alpha,alpha and
      alpha,beta dimers), a beta,beta dimer, most likely linked through intramembrane
      Cys(44) residues of two chains, is also formed. This dimer was also noted when
      digitonin-solubilized intact enzyme, and the trypsin-digested enzyme solubilized
      with digitonin or polyoxyethylene 10-laurylether were subjected to cross-linking,
      indicating that the detected beta,beta association was not due to random
      collisions. In the digested enzyme, K(+) but not Na(+) enhanced beta,beta dimer
      formation. The alternative cross-linking of beta-Cys(44) to a Cys residue of a
      transmembrane alpha-helix was antagonized specifically by K(+) or Na(+). The
      findings (i) indicate the role of beta,beta association in maintaining the
      minimum oligomeric structure of (alpha,beta)(2), (ii) provide further support for
      conformation-dependent flexibilities of the spatial relations of the
      transmembrane helices of alpha and beta and (iii) suggest the possibility of
      significant differences between the quaternary structures of the P-type ATPases
      that do and do not contain a beta subunit.

PMID- 11988104
TI  - High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is
      followed by rapid transporter-mediated export as a glutathione conjugate.
AB  - Sulphoraphane (SF), a naturally occurring isothiocyanate, is a potent
      anticarcinogen in animal experiments. The mechanism of action of sulphoraphane
      includes induction of Phase 2 detoxification enzymes, inhibition of carcinogen
      activating Phase 1 enzymes, induction of apoptosis and cell cycle arrest, and
      anti-inflammation. We have recently found that it was accumulated in mammalian
      cells by up to several hundred-fold over the extracellular concentration,
      primarily by conjugation with intracellular GSH. The intracellular accumulation
      levels of SF can reach millimolar concentrations. The anticarcinogenic activity
      of SF is at least partly dependent on its accumulation levels in cells. Here we
      show, however, that the accumulated SF was rapidly exported mainly in the form of
      GSH conjugate (GS-SF) in cultured human cells. It appeared that to sustain the
      intracellular accumulation levels required a continuous uptake of SF to offset
      the rapid export of SF/GS-SF. These findings may have important implications for
      the development of an effective dosing regimen for SF. Moreover, the export was
      temperature-sensitive and was inhibited by known inhibitors of membrane pumps,
      suggesting the involvement of such a pump in exporting accumulated SF/GS-SF.
      Indeed, studies with human leukemia cells (HL60) with or without overexpression
      of multidrug resistance associated protein-1(MRP-1) and human myeloma cells
      (8226) with or without overexpression of P-glycoprotein-1 (Pgp-1) indicated that
      both MRP-1 and Pgp-1 are involved in the export of intracellular SF/GS-SF.

PMID- 11988105
TI  - Contribution by different fuels and metabolic pathways to the total ATP turnover
      of proliferating MCF-7 breast cancer cells.
AB  - For the past 70 years the dominant perception of cancer metabolism has been that
      it is fuelled mainly by glucose (via aerobic glycolysis) and glutamine.
      Consequently, investigations into the diagnosis, treatment and the basic
      metabolism of cancer cells have been directed by this perception. However, the
      data on cancer metabolism are equivocal, and in this study we have sought to
      clarify the issue. Using an innovative system we have measured the total ATP
      turnover of the MCF-7 breast cancer cell line, the contributions to this turnover
      by oxidative and glycolytic ATP production and the contributions to the oxidative
      component by glucose, lactate, glutamine, palmitate and oleate. The total ATP
      turnover over approx. 5 days was 26.8 micromol of ATP.10(7) cells(-1).h(-1). ATP
      production was 80% oxidative and 20% glycolytic. Contributions to the oxidative
      component were approx. 10% glucose, 14% glutamine, 7% palmitate, 4% oleate and
      65% from unidentified sources. The contribution by glucose (glycolysis and
      oxidation) to total ATP turnover was 28.8%, glutamine contributed 10.7% and
      glucose and glutamine combined contributed 40%. Glucose and glutamine are
      significant fuels, but they account for less than half of the total ATP turnover.
      The contribution of aerobic glycolysis is not different from that in a variety of
      other non-transformed cell types.

PMID- 11988106
TI  - Cardiolipin prevents rate-dependent uncoupling and provides osmotic stability in
      yeast mitochondria.
AB  - The role of cardiolipin in mitochondrial function was studied by comparing the
      energy-transforming and osmotic properties of mitochondria isolated from the
      Saccharomyces cerevisiae cardiolipin synthase-null mutant crd1Delta, which has no
      cardiolipin, and the isogenic wild type. The results indicated that the
      importance of cardiolipin for energetic coupling strongly depends on the rate of
      oxidative phosphorylation, which was set by using NADH (maximal rate limited by
      coupling mechanism) or ethanol (moderate rate limited by electron supply) as a
      respiratory substrate, or by modulating the steady-state rate of NADH supply. The
      absence of cardiolipin resulted in only a small effect on oxidative
      phosphorylation proceeding at a moderate rate, but led to significant uncoupling
      (decreased ADP/O and increased state 4 respiration) at the maximal rate of
      respiration. This indicates that cardiolipin prevents rate-dependent uncoupling
      in the energy-transforming apparatus. This role of cardiolipin may derive from
      its strong interaction with, and modulation of the function of, respiratory
      complexes, and from its effects on the physical properties of the membrane. The
      importance of cardiolipin for mitochondrial osmotic properties was determined by
      comparing oxidative phosphorylation, release of matrix enzyme, shrinking ability
      and volume dynamics upon hypotonically induced swelling in crd1Delta and wild
      type mitochondria. Opening of the yeast mitochondrial unspecific channel (YMUC)
      in the wild-type and mutant mitochondria was also tested. It was found that the
      lack of cardiolipin strongly undermines the osmotic stability of the
      mitochondrial membrane.

PMID- 11988107
TI  - Characteristics and composition of the vitamin K-dependent gamma-glutamyl
      carboxylase-binding domain on osteocalcin.
AB  - Two different sites on vitamin K-dependent gamma-glutamyl carboxylase (VKC) are
      involved in enzyme-substrate interaction: the propeptide-binding site required
      for high-affinity substrate binding and the active site for glutamate
      carboxylation. Synthetic descarboxy osteocalcin (d-OC) is a low-K(m) substrate
      for the VKC, but unique since it possesses a high-affinity recognition site for
      the VKC, distinct from the propeptide which is essential as a binding site for
      VKC. However, the exact location and composition of this VKC-recognition domain
      on d-OC has remained unclear until now. Using a stereospecific substrate analogue
      [t-butyloxycarbonyl-(2S,4S)-4-methylglutamic acid-Glu-Val (S-MeTPT)] we
      demonstrate in this paper that the high affinity of d-OC for VKC cannot be
      explained by a direct interaction with either the active site or with the
      propeptide-binding site on VKC. It is shown using various synthetic peptides
      derived from d-OC that there are two domains on d-OC necessary for recognition:
      one located between residues 1 and 12 and a second between residues 26 and 39,
      i.e. at the C-terminal side of the gamma-carboxyglutamate (Gla) domain. Both
      internal sequences contribute substantially to the efficiency of carboxylation.
      On the basis of these data we postulate the presence of a second high-affinity
      substrate-binding site on VKC capable of specifically binding d-OC, which is the
      first vitamin K-dependent substrate of which the VKC binding domain is
      interrupted by the Gla domain.

PMID- 11988108
TI  - Use of neuroleptics in a general hospital.
AB  - BACKGROUND: This study investigates the clinical use of neuroleptics within a
      general hospital in acutely ill medical or surgical patients and its relation
      with dementia three months after admission compared with control subjects.
      METHODS: Cases were defined as every adult patient to whom a neuroleptic
      medication was prescribed during their hospitalization in our Hospital from
      February 1st, to June 30th, 1998. A control matched by age and sex was randomly
      selected among patients who had been admitted in the same period, in the same
      department, and had not received neuroleptics drugs (205 cases and 200 controls).
      Demographic, clinical and complementary data were compared between cases and
      controls. Crude odds ratios estimating the risk of dementia in non previously
      demented subjects compared with the risk in non-demented control subjects were
      calculated. RESULTS: 205 of 2665 patients (7.7%) received a neuroleptic drug. The
      mean age was 80.0 +/- 13.6 years and 52% were females. They were older and stayed
      longer than the rest of the population. Only 11% received a psychological
      evaluation before the prescription. Fifty two percent were agitated while 40% had
      no reason justifying the use of neuroleptic drug. Three months after neuroleptic
      use 27% of the surviving cases and 2.6% of the surviving controls who were judged
      non-demented at admission were identified as demented. CONCLUSIONS: The most
      common reason for neuroleptic treatment was to manage agitation symptomatically
      in hospitalised patients. Organic mental syndromes were rarely investigated, and
      mental status exams were generally absent. Most of neuroleptic recipients had
      either recognised or unrecognised dementia.

PMID- 11988110
TI  - Real-time RT-PCR analysis of mRNA decay: half-life of Beta-actin mRNA in human
      leukemia CCRF-CEM and Nalm-6 cell lines.
AB  - BACKGROUND: We describe an alternative method to determine mRNA half-life (t1/2)
      based on the Real-Time RT-PCR procedure. This approach was evaluated by using the
      beta-actin gene as a reference molecule for measuring of mRNA stability. RESULTS:
      Human leukemia Nalm-6 and CCRF-CEM cells were treated with various concentrations
      of Actinomycin D to block transcription and aliquots were removed periodically.
      Total RNA was isolated and quantified using the RiboGree&ncircledR; fluorescent
      dye with the VersaFluor Fluorometer System. One &mgr;g of total RNA was reverse
      transcribed and used as template for the amplification of a region of the beta
      actin gene (231 bp). To generate the standard curve, serial ten-fold dilutions of
      the pBactin-231 vector containing the cDNA amplified fragment were employed, beta
      actin mRNAs were quantified by Real-Time RT-PCR using the SYB&RcircledR; Green I
      fluorogenic dye and data analyzed using the iCycle iQ system software. Using this
      method, the beta-actin mRNA exhibited a half-life of 6.6 h and 13.5 h in Nalm-6
      and CCRF-CEM cells, respectively. The t1/2 value obtained for Nalm-6 is
      comparable to those estimated from Northern blot studies, using normal human
      leukocytes (5.5 h). CONCLUSIONS: We have developed a rapid, sensitive, and
      reliable method based on Real-Time RT-PCR for measuring mRNA half-life. Our
      results confirm that beta-actin mRNA half-life can be affected by the cellular
      growth rate.

PMID- 11988109
TI  - Schedule-selective biochemical modulation of 5-fluorouracil in advanced
      colorectal cancer--a phase II study.
AB  - BACKGROUND: 5-fluorouracil remains the standard therapy for patients with
      advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the
      biological modulation of 5-fluorouracil by methotrexate and leucovorin. This
      phase II study was initiated to determine the activity and toxicity of sequential
      methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with
      advanced colorectal cancer. METHODS: Ninety-seven patients with metastatic
      colorectal cancer were enrolled onto the study. Methotrexate--30 mg/m2 was
      administered every 6 hours for 6 doses followed by a 2 hour infusion of LV--500
      mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil-
      600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks
      until progression. RESULTS: The median age was 64 yrs (34-84) and the Eastern
      Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8%
      of patients. Partial and complete responses were seen in 31% of patients with a
      median duration of response of 6.4 months. The overall median survival was 13.0
      months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects
      were modest and included mucositis, nausea and vomiting. CONCLUSIONS: This phase
      II study supports previously reported data demonstrating the modest clinical
      benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with
      metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil
      modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress
      and may prove encouraging.

PMID- 11988122
TI  - TCM practice in China.

PMID- 11988124
TI  - The relationship between critical thinking and decision-making in respiratory
      care students.
AB  - INTRODUCTION: Respiratory therapists evaluate the condition of their patients,
      make decisions about the appropriateness of the treatment plan, provide care, and
      evaluate the outcomes of their decisions. To practice effectively they must think
      critically and make appropriate decisions. As educators make curriculum changes
      to improve students' decision-making (DM) skills, strategies to develop critical
      thinking (CT) have been proposed as one method of achieving that goal. This
      approach is based on the hypothesis that a positive relationship exists between
      DM and CT. The present study examines the relationship between CT and DM in
      respiratory care students. If there is a positive relationship between CT and DM,
      respiratory care training programs might improve the DM skills of future
      practitioners by providing instruction that improves CT. METHODS: Using a
      correlational research design, DM scores from the Clinical Simulation Self
      Assessment Examination (CSSAE) were compared with scores from the Watson-Glaser
      Critical Thinking Appraisal for 143 graduating respiratory care students from 10
      programs. Program directors completed a questionnaire and were then interviewed
      about the methods they employ to develop CT and DM in their students. RESULTS: A
      significant correlation between CT and DM was found for 110 students completing
      the Secure Form of the CSSAE (r = 0.32, p < 0.01). All programs used case studies
      and clinical simulations, and most used role modeling, computer-assisted
      instruction, patient rounds, small group discussion, and study skills courses. No
      differences were identified in the use of the CT and DM development strategies by
      different programs. CONCLUSIONS: The findings support the belief that students
      with strong CT proficiency make better clinical decisions. Assessment of CT
      proficiency could be used as one part of a process for evaluating prospective
      students and faculty for respiratory care programs. Program directors and faculty
      felt that case studies and clinical simulations are important strategies.

PMID- 11988125
TI  - Bedside spirometry in a tertiary care hospital: the cleveland clinic experience.
AB  - BACKGROUND: In contrast to outpatient, laboratory testing, which is performed by
      a small, dedicated group of pulmonary function technologists, inpatient, bedside
      spirometry at the Cleveland Clinic Hospital is performed less frequently and by a
      larger group of respiratory therapists with broader responsibilities. A 1998
      audit of bedside spirometry tests at our hospital showed that American Thoracic
      Society acceptability and reproducibility criteria were infrequently met (15% of
      instances). METHODS: To address that shortcoming, we initiated an improvement
      plan for bedside spirometry that included: (1) A didactic review of American
      Thoracic Society acceptability and reproducibility criteria that was videotaped
      and reviewed by all but one of the therapists performing spirometry; (2) limiting
      the number of operators to a "core group" to allow more tests per therapist; (3)
      producing printouts of the pulmonary function tests, which allows immediate
      review of volume-time and flow-volume curves; (4) central review of all tests by
      a pulmonary function technologist and feedback and constructive suggestions on
      test quality and reproducibility to operators. After initiating the program we
      performed a consecutive survey of all inpatient spirometry sessions performed
      from July 16, 1998, to March 2, 1999. RESULTS: During the survey period, 63.5% of
      the tests (n = 137) were deemed acceptable, exceeding the low baseline rate of
      15% (p < 0.001). Values for forced expiratory volume in the first second were
      reproducible in 83.9% of sessions. Values for forced vital capacity were
      reproducible in 80.3% of sessions. CONCLUSION: A quality improvement program for
      bedside spirometry testing that emphasizes training and routine feedback on test
      quality can enhance the quality of inpatient spirometry testing.

PMID- 11988126
TI  - A survey of physicians to identify their expectations of respiratory therapists
      in patient assessment.
AB  - INTRODUCTION: The exact role of respiratory therapists (RTs) in patient
      assessment is not well defined. The purpose of this study was to identify local
      physician expectations of RTs for the application and interpretation of various
      assessment procedures. METHODS: A survey was developed that called for physicians
      to indicate on a scale of 1 to 5 (1 = never, 2 = rarely, 3 = occasionally, 4 =
      often, and 5 = always) how important they perceive it is for RTs to be able to
      interpret or perform 20 commonly used patient assessment tests or procedures. The
      survey was mailed to 25 physicians who care for patients in the medical and
      surgical intensive care units at Loma Linda University Medical Center and the
      Jerry L Pettis Veterans Administration Memorial Medical Center. RESULTS: Twenty
      (80%) of the surveys were returned. The assessment procedures rated highest were:
      to assess lung sounds (4.8), to interpret arterial blood gas values (4.5), to
      interpret pulmonary function tests (4.4), to assess and interpret vital signs
      (4.4), and to interview patient to clarify symptoms (4.3). The procedures
      consistently rated low were: to interpret echocardiography (2.5), to assess
      abdomen (2.3), to interpret sleep studies (2.2), and to interpret
      electroencephalogram (1.7). A total expectation score for each completed survey
      was determined by adding the scores from each of the 20 assessment procedures.
      The average +/- SD total score was 66.8 +/- 10.4 on a scale of 20 to 100. The
      total expectation score did not vary by years of experience in patient care or
      type of medical specialty. CONCLUSIONS: The results indicate that the physicians
      completing our survey generally have high expectations of RTs for the application
      of patient assessment techniques that involve direct evaluation of lung
      performance or condition.

PMID- 11988127
TI  - Chronic obstructive pulmonary disease: on an exponential curve of progress.
AB  - The last 50 years have witnessed major progress in our understanding of the
      underlying nature of chronic obstructive pulmonary disease (COPD) and approaches
      to care. During the last 10 years, however, there has been an explosive expansion
      of knowledge related to this disorder. Large-scale epidemiologic studies show
      that COPD is the fourth leading cause of death in the United States and will be
      the fifth leading health burden worldwide by the year 2020. We have also learned
      that COPD is an inflammatory disorder of small airways, which presents new
      opportunities for therapy involving interfering with the early components of the
      inflammatory cascade. Unfortunately, most clinicians fail to perform spirometric
      screening of at-risk individuals, so most patients first present with COPD during
      a sudden exacerbation of the disease. Worldwide interest is emerging in promoting
      earlier diagnosis and finding new pharmacologic interventions to halt the
      progression of airway and parenchymal damage. In this review, evidence is
      presented that we are on the upward limb of an exponential curve of progress in
      managing COPD, which will produce major advances in our ability to recognize and
      treat this disorder in its earliest stages.

PMID- 11988129
TI  - Advances in sex-based analysis.

PMID- 11988130
TI  - CDC contributions to women's health: focusing on prevention in midlife.

PMID- 11988131
TI  - Toward optimal health: the experts discuss depression. Interview by Jodi Godfrey
      Meisler.

PMID- 11988132
TI  - Combination treatment of osteoporosis: a clinical review.
AB  - OBJECTIVE: Because of the limited efficacy of available agents and to limit
      toxicity, there is considerable interest in combination pharmacotherapy for
      osteoporosis. METHODS: A search was performed for randomized controlled trials in
      MEDLINE (1966-present) using the keywords osteoporosis treatment and combination.
      RESULTS: Twenty-four randomized controlled trials evaluated osteoporosis
      medications in combination. Study duration ranged from 1 to 4 years. No serious
      adverse events were definitively attributable to study drugs. Fracture reduction
      outcome is not shown for any combination regimen. The literature was mixed
      regarding bone density augmentation. Combinations of nandrolone decanoate plus
      calcitonin, calcitonin plus growth hormone (GH), or pamidronate plus GH may be
      contradictory or detrimental to bone mineral density (BMD). For postmenopausal
      osteoporosis or osteopenia, four combinations appear to increase hip and lumbar
      BMD: 10 mg alendronate with 0.625 mg conjugated equine estrogens (CEE), cyclic
      etidronate with 0.625mg CEE, 10 mg alendronate with 2 mg estradiol (E(2)), and
      tibolone with fluoride. For steroid-related osteoporosis, intermittent etidronate
      with fluoride increases lumbar BMD. CONCLUSIONS: The few trials including Food
      and Drug Administration (FDA)-approved medications suggest that 10 mg/day
      alendronate with estrogen (equivalent of 0.625 mg CEE daily) can increase BMD
      moreso than each medication given singly in postmenopausal osteoporotic women.
      Estrogen dose and type must be controlled in future trials. Long-term safety data
      are lacking. The utility of these combinations rests on whether bone density
      changes will translate into decreased fracture rates.

PMID- 11988133
TI  - The roles of estrogen and progesterone in regulating carbohydrate and fat
      utilization at rest and during exercise.
AB  - OBJECTIVE: Compared with men, women use more fat and less carbohydrate to fuel
      exercise at the same relative intensity. Circulating levels of estrogen and
      progesterone are likely to play an important role in explaining this gender
      difference in exercise substrate utilization. METHODS: Studies, mainly using
      animal models, have shown that estrogen increases fatty acid availability
      (lipolysis) and decreases carbohydrate availability and uptake. Studies conducted
      in humans corroborate the reduction in carbohydrate turnover and oxidation in the
      presence of estrogen, but the impact on fatty acid availability and utilization
      is less clear. RESULTS: The effect of circulating estrogen may be mediated, at
      least in part, by changes in the sensitivity of stored carbohydrate and lipids to
      mobilization in response to epinephrine. The role of progesterone in metabolic
      regulation during exercise has not been systematically studied in humans.
      CONCLUSIONS: Understanding the role of the ovarian hormones in fat and
      carbohydrate metabolism during exercise may have practical applications in terms
      of understanding the metabolic consequences of amenorrhea, menopause, and hormone
      replacement therapy (HRT).

PMID- 11988134
TI  - Correlates of physical activity among women from diverse racial/ethnic groups.
AB  - OBJECTIVE: Women have lower rates of participation in leisure time physical
      activity than men and have been studied to a lesser extent than men. Because
      physical activity plays a vital role in overall health, it is important to
      identify factors than can help increase physical activity rates for women.
      METHODS: Defining and understanding correlates of physical activity is critical
      for at-risk populations and for planning effective interventions. This paper
      reviews research conducted in the past two decades on correlates of physical
      activity in women. An ecological model with an added physical environment
      component was used to organize the correlates. Studies conducted among adult
      white, black, American Indian, Asian, and Hispanic women are included. A total of
      91 studies were reviewed. Many studies included white women, fewer studies
      included black and Hispanic women, and even fewer included American Indian women,
      and only 3 studies included Asian women. RESULTS: The correlates most studied are
      sociodemographic variables, with nonwhite race, lower educational levels, and
      older age most consistently associated with lower levels of physical activity.
      Few studies focused on environmental and policy correlates. Social support was an
      overwhelmingly positive determinant of physical activity for all groups of women.
      CONCLUSIONS: Based on these findings, we recommend that future research include
      more diverse groups of women and evaluate modifiable factors, such as
      psychological, interpersonal, and environmental correlates. Future research also
      should include more intervention and longitudinal studies.

PMID- 11988135
TI  - Replacement surgery and silicone gel breast implant rupture: self-report by women
      after mammoplasty.
AB  - BACKGROUND: This study examined the prevalence of revision surgery in which
      silicone gel breast implants were either removed (explanted) or replaced in a
      cohort of women from Birmingham, Alabama. The main reason leading up to the
      surgery and the prevalence of ruptured implants reported after explantation are
      described. METHODS: Data were collected from telephone interviews with 907 women
      previously identified in a larger cohort study of women with breast implants.
      Women who reported breast surgeries subsequent to their index mammoplasty were
      asked to consent to retrieval of the surgical records describing the surgery.
      RESULTS: Surgery in which a silicone gel breast implant was removed or replaced
      was reported by 33% of the 907 women in this cohort. The most common reason for
      surgery was problems with the implant that affected the breast (103 of 303
      surgeries). Of the 303 women reporting surgery, 145 (48%) reported knowing after
      a surgery that an implant was ruptured when it was removed, and 171 (56%)
      reported knowing that an implant was ruptured or leaking. Overall, 16% of the 907
      women reported knowing that either of their implants was ruptured after any
      surgery. At least one surgical record was retrieved for 165 (54%) of the 303
      women reporting surgery. Among these women, the rupture rate was 69 of 165 (42%)
      according to the surgical record and 85 of 165 (51.5%) according to self-reports,
      a statistically significant difference (p = 0.008 from McNemar's test). The mean
      time from implantation to surgery was 11.5 years among women reporting surgery
      and estimated at 21.4 years for all women. CONCLUSIONS: A third of the women in
      this cohort underwent additional surgery after the initial mammoplasty, and
      nearly half who underwent surgery reported that their implants were found to be
      ruptured when removed. Women considering silicone gel breast implants should be
      informed of the risk of additional surgeries and of the potential risk of breast
      implant rupture.

PMID- 11988136
TI  - The acceptability of self-collected samples for HPV testing vs. the pap test as
      alternatives in cervical cancer screening.
AB  - OBJECTIVE: To explore the acceptability of the self-collection of samples for
      human papillomavirus (HPV) testing in comparison with that of the Pap test.
      METHODS: The study population consisted of 1069 women 20 years and older who were
      eligible for coverage through the Mexican Institute of Social Security (IMSS).
      These women were randomly selected among participants in a larger study to
      evaluate the use of HPV testing as an alternative in cervical cancer screening.
      All participants provided a self-collected vaginal sample for HPV testing
      according to explicit instructions and underwent a Pap test. Afterwards, each
      woman was interviewed about her experience and opinion regarding the two
      procedures. Acceptability was measured by a calculated score based on discomfort,
      pain, embarrassment, privacy, perception of personal treatment during the Pap
      test, and understanding of how to perform the self-sampling method. RESULTS:
      Ninety-three percent of women experienced sufficient privacy with the Pap test,
      whereas 98% of women reported that privacy with the self-sampling procedure was
      acceptable. The Pap test consistently provoked more discomfort, pain, and
      embarrassment than self-sampling. Sixty-eight percent of the women who indicated
      a test preference chose self-sampling. Preference for this method was positively
      associated with monthly household income. Women reported a preference for self
      sampling because it is more comfortable (71.2%) and causes less embarrassment
      (55.8%). CONCLUSIONS: Self-sampling is more acceptable than the Pap test and
      could improve coverage rates of early detection programs. The incorporation of
      self-collected samples to detect HPV could encourage participation in screening
      programs among those women who reject the Pap test because of the necessary
      pelvic examination.

PMID- 11988137
TI  - Development of a sexual function questionnaire for clinical trials of female
      sexual dysfunction.
AB  - OBJECTIVE: To better evaluate efficacy in clinical trials of drugs as potential
      treatments for female sexual dysfunctions (FSD), a brief, multidimensional
      measure of female sexual function was developed. METHODS: Data from
      semistructured interviews with 82 women with or without FSD, aged 19-65 years,
      generated a pool of 61 items that addressed aspects of female sexual function. On
      review by a panel, individual items were selected for face validity and clinical
      relevance. Thirty-one items were used as a sexual function questionnaire (SFQ-V1)
      in two multicenter, phase II clinical trials totaling 781 women with FSD.
      Normative data were generated from a sample of 201 women without FSD. RESULTS:
      Factor analysis produced seven domains of female sexual function: desire,
      physical arousal-sensation, physical arousal-lubrication, enjoyment, orgasm,
      pain, and partner relationship. The internal consistency of the domains ranged
      from 0.65 to 0.91, and test-retest reliability ranged from 0.21 to 0.71 for
      Cohen's weighted kappa and 0.42 to 0.78 for Pearson's correlation coefficient.
      There was a significant difference between the baseline mean SFQ domain scores of
      patients with FSD compared with those of women without FSD (p < 0.0001). End-of
      study SFQ scores were significantly different for women who reported improvement
      vs. women who reported no improvement (p < 0.001). CONCLUSIONS: The SFQ produced
      seven domains of female sexual function with excellent internal consistency,
      moderate to good reliability, excellent discriminant validity, and sensitivity.
      The results suggest that the SFQ may be a valuable new tool for evaluating and
      diagnosing subsets of FSD and, ultimately, for evaluating treatments of these
      disorders.

PMID- 11988138
TI  - Raloxifene is associated with less side effects than tamoxifen in women with
      early breast cancer: a questionnaire study from one physician's practice.
AB  - OBJECTIVE: Selective estrogen receptor modulators (SERMs) are being used
      increasingly for the prevention and treatment of breast cancer. The currently
      available SERMs, tamoxifen and raloxifene, are both associated with
      antiestrogenic side effects that can be bothersome. However, no data exist on how
      they compare in this regard. We conducted a retrospective, questionnaire-based
      study to answer this question. METHODS: Women with early breast cancer in one
      physician's practice who had received either or both of these drugs were surveyed
      using a self-administered questionnaire. Respondents graded the frequency and
      severity of side effects related to estrogen deprivation, such as vaginal
      dryness, mood changes, hot flashes, weight gain, and changes in libido, as well
      as other side effects, such as vaginal discharge. They were separated into three
      groups for analysis (group 1, tamoxifen only; group 2, raloxifene only; group 3,
      both drugs). Side effects graded 4 or 5 (or weight gain >10 pounds) were
      considered severe. RESULTS: Two hundred sixty-four questionnaires were available
      for analysis. Women on raloxifene had a shorter average duration of therapy. In
      comparing the tamoxifen and raloxifene groups, vaginal discharge, severe hot
      flashes, and weight gain of >10 pounds were significantly more frequent with
      tamoxifen. However, weight gain was also related to the duration of therapy with
      either drug. CONCLUSIONS: In this observational study, antiestrogenic side
      effects were common with either tamoxifen or raloxifene. Raloxifene is associated
      with significantly less vaginal discharge and severe hot flashes than tamoxifen
      in women with early breast cancer. Although weight gain of >10 pounds may also
      occur less frequently on this drug, this may be confounded by the shorter average
      duration of raloxifene therapy.

PMID- 11988139
TI  - Women's Health LiteratureWatch.

PMID- 11988140
TI  - [Towards the future with confidence. It's time for validation].

PMID- 11988141
TI  - [Etiologic implication of foods in atopic dermatitis: evidence in favor].
AB  - Some of the immunopathologic mechanisms involved in IgE responses are currently
      being identified; Th2 lymphocytes are known to be activated in patients with
      atopic dermatitis with subsequent production of the cytokines interleukin (IL)-4
      and IL-5, which are responsible for IgE production and eosinophil recruitment.
      Nevertheless, T cell activation in this disease takes place in two phases. In the
      first phase, Th2 cells are activated and IL-4, IL-5 and IL-13 are produced; this
      first stage is produced with the initial activation induced by the antigen. In
      the second phase there are chronic lesions, Th1 lymphocytes are activated and IFg
      is produced. This chronic phase is associated with the presence of eosinophils
      and macrophages that produce IL-12.Numerous articles have demonstrated food
      sensitization to be an etiopathogenic factor in atopic dermatitis. The prevalence
      of sensitization varies, depending on the patient's age and the severity of the
      disease. Children with moderate-to-severe atopic dermatitis have been observed to
      have a positive skin test and high IgE concentrations to various foods.
      Nevertheless, a positive skin test to foods in such children does not always
      implicate these foods as the cause of the clinical manifestations; moreover, in
      children showing subsequent tolerance to these foods, skin tests can sometimes
      remain positive and high levels of specific IgE can persist. It is now known that
      IgE not only participate in the degranulation of mastocyte cells but also in
      reactions mediated by T cells and other antigen-presenting cells (dendritic
      cells) which have high-affinity receptors for IgE.The immediate IgE response is
      well known but it is also known that in addition to the immediate response, a
      delayed response is also involved, evidenced by the presence of antigen-specific
      T cells to foods or other allergens such as inhalant allergens. After a strict
      exclusion diet, children with atopic dermatitis and sensitivity to foods such as
      milk, egg, flour and soya can develop tolerance; for this reason provocation
      tests with the food in question should be repeated every 2-3 years. In children
      with sensitivity to other foods such as dried fruits, fish, and shellfish,
      sensitivity can sometimes persist into adulthood without tolerance being
      achieved. In conclusion, there are two groups of children with atopic dermatitis.
      One group consists of those with atopic dermatitis (allergic disease), which is
      characterized by early development, high IgE titers, the presence of antigen
      specific IgE to allergens and a family history of atopy and which is clinically
      moderate or severe. Early diagnosis and treatment are important in these
      children, as is the prevention of progression of the disease to bronchial asthma.
      The other group consists of children whose dermatitis is clinically atopic in
      terms of its localization and morphology, who have no demonstrable allergic
      disease and whose management differs from that in children presenting allergic
      disease.

PMID- 11988142
TI  - [Etiologic implication of foods in atopic dermatitis: evidence against].
AB  - Atopic dermatitis is a typical chronic inflammatory skin disease that usually
      occurs in individuals with a personal or family history of atopy. Children with
      atopic dermatitis frequently present IgE-mediated food sensitization, the most
      commonly involved foods being egg and cow's milk. However, controversy currently
      surrounds whether food allergy is an etiological factor in atopic dermatitis or
      whether it is simply an associated factor, accompanying this disease as one more
      expression of the patient's atopic predisposition. Approximately 40 % of neonates
      and small children with moderate-to-severe atopic dermatitis present food allergy
      confirmed by double-blind provocation tests but this allergy does not seem to be
      the cause of dermatitis since in many cases onset occurs before the food
      responsible for allergic sensitization is introduced into the newborn's
      diet.Studies of double-blind provocation tests with food in patients with atopic
      dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated
      allergy. These reactions occur between 5 minutes and 2 hours and present mainly
      cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a
      lesser extent, digestive manifestations (nausea, vomiting, abdominal pain,
      diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing,
      coughing). However, these reactions do not indicate the development of
      dermatitis.Some authors believe that responses to the food in provocation tests
      may also be delayed, appearing mainly in the following 48 hours, and clinically
      manifested as exacerbation of dermatitis. However, delayed symptoms are difficult
      to diagnose and attributing these symptoms to a particular foodstuff may not be
      possible.Delayed reactions have been attributed to a non-IgE-mediated
      immunological mechanism and patch tests with food have been proposed for their
      diagnosis. In our experience and in that of other authors, the results of patch
      tests with cow's milk do not seem very specific and could be due, at least in
      part, to the irritant effect of these patches on the reactive skin of children
      with atopic dermatitis.The involvement of foods in atopic dermatitis will always
      be difficult to demonstrate given that an exclusion diet is not usually required
      for its resolution. Food is just one among several possible exacerbating factors
      and consequently identification of its precise role in the course of the disease
      is difficult. Further double-blind prospective studies are required to
      demonstrate the effectiveness of exclusion diets in the treatment of atopic
      dermatitis.Apart from the controversy surrounding the etiological role of foods,
      the most important point in atopic dermatitis is to understand that the child is
      atopic, that is, predisposed to developing sensitivity to environmental
      allergens; in the first few years of life to foods and subsequently to
      aeroallergens. Consequently, possible allergic sensitization to foods should be
      evaluated in children with atopic dermatitis to avoid allergic reactions and to
      prevent the possible development of allergic respiratory disease later in life.

PMID- 11988143
TI  - [Role of aeroallergens in the etiopathogenesis of atopic dermatitis].
AB  - Atopic dermatitis is a chronic relapsing inflammatory skin disease. It is most
      frequent in childhood and its clinical manifestations vary with age. The
      etiopathogenic mechanisms that explain this process are still poorly understood;
      several studies performed in adults speculate on the possible role of
      aeroallergens through direct contact with the skin but, because the etiology of
      this disease varies with age, studies in children of different ages are required.
      AIMS: (i) To determine whether children with atopic dermatitis are sensitized to
      inhalant allergens. (ii) To determine whether these inhalant allergens cause
      dermatitis or whether they provoke allergic respiratory disease (asthma,
      rhinitis) concomitant with atopic dermatitis. (iii) To evaluate whether
      sensitization to a particular allergen takes place at any age or whether there
      are differences according to age. MATERIAL AND METHODS: This study was performed
      in the following groups: (i) 64 children with atopic dermatitis, divided into two
      subgroups, one consisting of 37 children who also presented allergic respiratory
      disease (asthma, rhinitis) (AR) and another subgroup of 27 patients who presented
      atopic dermatitis only. (ii) CONTROL GROUP: eight children who presented AR only,
      to determine whether this group reacted to patch testing with inhalant allergens.
      (iii) CONTROL GROUP: seven healthy children to rule out non-specific positive
      tests in the non-atopic population. All groups were divided by age according to
      the phases of atopic dermatitis: early childhood phase (< 2 years): 21, childhood
      phase (2-10 years): 37, adolescent phase (> 10 years): 21. In all children total
      serum IgE determination (RIA), allergen-specific IgE determination (RAST), prick-
      and patch test were performed. In the three tests the same allergens were used,
      consisting of the usual components of standardized inhalant and food allergens.
      When the results of patch testing were positive, biopsy and histopathological
      analysis were performed and monoclonal antibodies were used to determine
      reproducibility of the eczematous lesion. RESULTS: Sensitization was found to
      differ among patients with atopic dermatitis according to whether they presented
      respiratory symptoms and according to age with a clear predominance of food
      sensitization in the group aged less than 2 years. In the group aged 2-10 years,
      mixed sensitization predominated, mainly because of simultaneous respiratory
      involvement, but it is highly probably that inhalant allergens participate in the
      etiopathogenesis of atopic dermatitis. In children aged more than 10 years
      sensitization to inhalant allergens predominated as most presented respiratory
      symptoms. Patch testing was positive in 34.3 % of patients with atopic dermatitis
      and approximately half were positive to dust mites. The patch test is of great
      diagnostic value in atopic dermatitis and none of the tests were positive in the
      control group. All the biopsies of patch tests with inhalant allergens reproduced
      the lesions typical of eczema, demonstrating their involvement in the
      etiopathogenesis of dermatitis.

PMID- 11988144
TI  - [New horizons in the treatment of atopic dermatitis].
AB  - Nearly fifty years after their introduction, corticoids continue to be one of the
      main pillars of dermatological therapy in general and in atopic dermatitis in
      particular. However, their use is limited by local and systemic adverse
      effects.There is enormous demand for anti-inflammatory agents not belonging to
      the corticoid group that would be useful in the different inflammatory
      dermatoses.In the last few years the therapeutic arsenal for atopic dermatitis
      has increased with two distinct groups of drugs: topical immunomodulators and
      leukotriene inhibitors. Both groups of drugs are new and new compounds belonging
      to these types of drugs will probably appear in the next few years.Among the
      alternatives to corticoids are the immunomodulators and the most promising of
      these are macrolide antibiotics. Tacrolimus (FK 506) and pimecrolimus (ASM 981)
      belong to this group of substances with a high capacity to inhibit T lymphocyte
      activation. Although they also act on other cells playing a role in atopic
      dermatitis (mastocytes, Langerhans' cells, B lymphocytes) their action on T
      lymphocytes seems to be the most important. In T lymphocytes, these drugs act by
      inhibiting the action of calmodulin, a vital enzyme in the activation chain of
      these cells that ends in the production of interleukin 2 and other
      proinflammatory cytokines.The accumulated evidence of the various publications
      seems to indicate that tacrolimus is a safe and effective treatment of atopic
      dermatitis in patients aged 2 years or more. The drug was approved for clinical
      use 3 years ago in Japan and more than 1 year ago in the United States. The
      number of randomized clinical trials comparing this drug with placebo or various
      corticoids demonstrate that its action is overwhelming. Its anti-inflammatory
      action is similar to that of high-potency topical corticoids. Two doses daily are
      required and the drug has been tested in patients with moderate-to-severe atopic
      dermatitis. Published data from more than 10,000 patients guarantee its safety.
      The most frequent short-term adverse effect is a burning sensation in the site of
      application lasting a few minutes.Pimecrolimus has not yet been commercialized in
      any country and is currently undergoing phase III clinical investigations. It has
      been tested in three clinical trials in patients aged more than 3 months old with
      mild-moderate atopic dermatitis. Its safety profile is good and similar to that
      of tacrolimus.The number and quality of the data provided by studies of treatment
      with leukotriene inhibitors (zafirlukast, montelukast and zileuton) is much lower
      but these substances seem to warrant further investigation. Only five small
      series undergoing treatment with these products have been published.

PMID- 11988145
TI  - [Latex allergy].

PMID- 11988146
TI  - [Peculiarities of latex allergy and preventive measures in the pediatric age
      group].
AB  - Latex allergy can be considered a problem of public health in at-risk
      populations. Although the figures on prevalence vary, approximately 1 % of the
      general population is sensitized to latex. To date, two determining factors for
      latex sensitization have been identified: an atopic predisposition and the number
      of operations. Among atopic patients or those at-risk for allergy, the prevalence
      of latex sensitization is between 3 and 20 times higher than that among the
      general population. Nevertheless, the effect of this factor seems to be
      modulatory and the determining factor seems to be the number of operations that
      children have undergone; the critical number is 5-6 interventions, after which
      the probability of sensitization increases considerably.All children who have
      undergone multiple operations should be considered as being at-risk. Children
      with spina bifida are especially at-risk. The reasons for this are still a matter
      of debate: the disease itself has been postulated as a specific risk factor,
      although other, possible associated factors could be determinant in triggering
      latex sensitization (the presence of a ventricular-peritoneal shunt, age at which
      surgery was performed, type of operation, etc.). Children with spina bifida and
      latex allergy show considerable differences in type of allergic sensitization;
      these differences seem to result from the different route of sensitization and
      could explain the variations observed in the clinical manifestations between
      children and adults: children become sensitized mainly by direct contact between
      latex particles and blood vessels and open mucosae while in adults the process
      takes place transcutaneously or by inhalation of aerosol particles. Consequently,
      the most frequent manifestation in children is urticaria while contact dermatitis
      and respiratory symptoms predominate in adults. Studies performed with
      immunoblotting have confirmed that children have IgE that almost constantly
      recognize low molecular weight latex proteins (14, 15 and 27 Kd) while this
      finding is less frequent in adults.The preventive measures in the pediatric
      population focus on avoidance of latex, especially in hospitals. Today, latex is
      ubiquitous, making complete avoidance difficult. When necessary, and whenever a
      latex-free environment cannot be guaranteed, presurgical medication can be used,
      although its utility is debatable. Although further studies are required,
      specific immunotherapy is one therapeutic possibility that may in future be used
      in children with latex allergy.

PMID- 11988147
TI  - [Latex-fruit syndrome].
AB  - During the last decade, latex IgE-mediated allergy has been recognized as a very
      important medical problem. At the same time, many studies have dealt with
      allergic cross-reactions between aeroallergens and foods. In this context, there
      is clear evidence now on the existence of significant clinical association
      between latex and fruit allergies. Therefore, a latex-fruit syndrome has been
      postulated.Several studies have demonstrated that from 20% to 60% of latex
      allergic patients show IgE-mediated reactions to a wide variety of foods, mainly
      fruits. Although implicated foods vary among the studies, banana, avocado,
      chestnut and kiwi are the most frequently involved. Clinical manifestations of
      these reactions may vary from oral allergy syndrome to severe anaphylactic
      reactions, which are not uncommon, thus remarking the clinical relevance of this
      syndrome.The diagnosis of food hypersensitivities associated to latex allergy is
      based on the clinical history of immediate adverse reactions, suggestive of an
      IgE-mediated sensitivity. Prick by prick test with the fresh foods implicated in
      the reactions shows an 80% concordance with the clinical diagnosis, and therefore
      it seems to be the best diagnostic test available nowadays in order to confirm
      the suspicion of latex-fruit allergy. Once the diagnosis is achieved, a diet free
      of the offending fruits is mandatory.Recently, some of the common allergens
      responsible for the cross-reactions among latex and the fruits most commonly
      implicated in the syndrome have been identified. Class I chitinases, with an N
      terminal hevein like domain, which cross-react with the major latex allergen
      hevein, seem to be the panallergens responsible for the latex-fruit syndrome.

PMID- 11988148
TI  - [Treatment perspectives: immunotherapy with latex].
AB  - Latex allergy currently constitutes a serious problem because of the severity of
      its symptoms and the at-risk groups it affects. Since complete avoidance of this
      substance is practically impossible, in the last few years intense efforts have
      been made to standardize a latex extract with the aim not only of improving
      clinical diagnosis but also of being able to offer other therapeutic
      alternatives, such as specific immunotherapy.Since 1998, reports of immunotherapy
      with oral (three patients) subcutaneous (one patient) and sublingual latex
      desensitization (one patient) have been published. In all cases, clinical
      improvement was evident. In 2000, Laynadier published the first pilot study, a
      phase IIB multicenter, randomized, double-blind, placebo-controlled trial that
      evaluated the efficacy and safety of specific immunotherapy with latex in
      patients with occupational allergy. Twenty health care workers without obvious
      latex exposure and with latex allergy-induced symptoms of rhinitis and/or asthma
      were included. Treatment started with a 2-day course of rush immunotherapy in
      hospital and maintenance therapy was continued for 1 year. Efficacy was assessed
      by symptom and medication scores and by variation in the conjunctival reactivity
      threshold. The safety of the extract was also evaluated. In the overall analysis
      of symptom score, the treated group showed a marked improvement and the
      medication score was significantly lower in patients in the active treatment
      group than in the placebo group. Concerning safety, almost half the patients
      receiving active treatment showed local reactions starting with the first
      injection and four of the nine patients in this group suffered moderate-to-severe
      systemic reactions. In view of this first clinical trial, it can be concluded
      that this treatment is effective but that its tolerance is low.A second clinical
      trial with the same characteristics and extract is currently underway. Its aim is
      to validate the previous protocol, confirm the efficacy of specific immunotherapy
      with latex, improve its safety and, if possible, determine the optimal dose.J.
      Sastre et al. have recently (Formigal 2002) presented the results of the first
      double-blind study with latex immunotherapy using an extract standardized by the
      ALK-Abello-Espana group. The authors included 24 patients with latex
      sensitization and symptoms of occupational allergy. To diagnose respiratory
      allergy, an inhalation challenge was performed in a closed 7-m2 chamber and, in
      case of contact urticaria, glove-wearing and rubbing tests were performed, using
      a vinyl glove as negative control. Treatment consisted of a first phase of
      incremental doses for 14 weeks, with 18 injections, followed by maintenance doses
      for 6 months. Sixteen patients received active treatment and 8 received placebo.
      Of the 578 doses administered, adverse effects were observed in 41 (7.1 %). There
      were 21 immediate systemic reactions (5.7 % of the doses) and 10 delayed systemic
      reactions (2.6 % of the doses). Adverse effects were more frequent in patients
      with underlying respiratory disease (p < 0.05). After 6 months' treatment, a
      clear improvement in the cutaneous response index was found in the active
      treatment group and in the rubbing and glove-wearing tests. The authors conclude
      that the immunotherapy tested was a high-risk treatment and that the greatest
      clinical improvement was found in cutaneous symptoms.In conclusion, although
      effective, latex immunotherapy is currently a high-risk treatment.

PMID- 11988149
TI  - [Blood pressure differences between consecutive days of ambulatory monitoring in
      hypertensive patients: the ABPM effect].
AB  - BACKGROUND: Ambulatory blood pressure monitoring is a method of blood pressure
      assessment that compensates for some of the limitations of office values. While a
      white-coat pressor effect on conventional determination has been defined and
      frequently used for the improved evaluation of hypertensive patients, there is no
      evidence that the ambulatory technique could also influence blood pressure.
      PATIENTS AND METHOD: Aimed at testing and quantifying the extent and duration
      over time of a possible pressor effect due to ambulatory monitoring, we studied
      387 mild-to-moderate hypertensive patients (160 men), aged 54.2 (14.3) (mean
      [SD]). Blood pressure and heart rate were measured at 20-min intervals during the
      day and at 30-min intervals at night for 48 consecutive hours, and physical
      activity was simultaneously evaluated at 1-min intervals by means of a wrist
      actigraph. One third of patients were evaluated twice or more times. RESULTS: In
      hypertensive patients who were evaluated for the first time, results indicate a
      highly significant (p < 0.001) reduction, in the second day of monitoring as
      compared to the first, in the diurnal mean of systolic and diastolic blood
      pressure, but not in heart rate or physical activity. This pressor effect remains
      significant for at least the first 5 hours of monitoring. The nocturnal mean of
      blood pressure was, however, similar in the two days of sampling. This ambulatory
      monitoring effect could not be observed when patients were evaluated following
      the same sampling scheme at the second or further times. CONCLUSIONS: Ambulatory
      monitoring for 48 consecutive hours reveals a statistically significant pressor
      response that could reflect a novelty effect in the use of the monitoring device
      for the first time. This effect has notable implications in both research and
      clinical daily practice, both for proper diagnosis of hypertension and evaluation
      of treatment efficacy.

PMID- 11988150
TI  - [Deep venous thrombosis of lower extremities in an Emergency Department. Utility
      of a clinical diagnosis model].
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a difficult to diagnostic disease. The
      aim of this study was to determine the utility and accuracy of a risk
      stratification questionnaire and a diagnostic strategy, which were applied to
      patients with suspected DVT on lower extremities in an emergency department.
      PATIENTS AND METHOD: A prospective cohort study was performed in 569 outpatients
      with clinical suspected DVT during 14 months. The applied questionnaire
      stratified patients into three pre-test probability categories. Items included
      signs, symptoms, risk factors and potential alternative diagnosis, which were
      based on a modified Wells clinical model. DVT was diagnosed by the combined use
      of clinical model, compression ultrasonography (CUS) and follow-up CUS one week
      later in those moderate-high risk patients with an initial normal test. These
      patients were followed over three months for the development of venous
      thromboembolic complications. RESULTS: Two hundred three (35.7%) patients were
      classified as having a low, 186 (32.7%) moderate and 180 (31.6%) high clinical
      probability. Overall, DVT was diagnosed in 153 patients (26%; CI95%, 23.2-30.7%):
      144 (96%) at the initial CUS, 6 (3.5%) at the second testing and 3 over the 3
      month follow-up period. 22 patients had a low pretest probability (11%; CI95%, 7
      16%), 43 (23%; CI95%, 17-30%) moderate, and 88 (49%; CI95%, 41-56%) high pretest
      probability. The difference in the prevalence of DVP among risk categories was
      significant (p < 0.00001). When the high and moderate groups were joined, the
      model had a 86% sensitivity, a 90% negative predictive value and a 43%
      specificity for diagnosis of DVT. CONCLUSIONS: The clinical model used in this
      study is accurate and feasible, though it is not enough to take clinical
      decisions. The diagnostic strategic used is effective but not efficient.

PMID- 11988151
TI  - [Effects of kidney and pancreas transplantation on neurophysiological rates of
      polyneuropathy and autonomous cardiac function in diabetic patients with end
      stage renal disease].
AB  - BACKGROUND: Patients with type 1 diabetes mellitus (DM1) and end-stage renal
      disease (ESRD) usually exhibit a severe polyneuropathy (PNP) whose progression
      can be halted after kidney and pancreas transplantation (KPT). We studied the
      evolution of both PNP and autonomous cardioregulatory function (ACF) in patients
      with DM1 and ESRD within the first year after KPT. PATIENTS AND MEHTOD: The study
      was carried out in 26 patients who underwent KPT and whose organs were
      functioning normally at least during one year after KPT. They were examined
      neurophysiologically in three different periods: a) before KPT; b) 1-3 months
      after KPT, and c) 12 months after KPT. We evaluated PNP by measuring the
      conduction velocity (CV) and the amplitude of the compound action potentials
      (ACAP) of common peroneal, posterior tibial and sural nerves. ACF was evaluated
      by measuring the change in the interval separating two consecutive QRS complexes
      in the electrocardiogram during quiet breathing and Valsalva manoeuvre. RESULTS:
      All patients had a severe PNP before KPT. Ten patients (38.4%) showed a
      significant reduction in ACAP and ACF in the exam carried out within 1 to 3
      months after KPT, whereas all patients showed an increase in the CV, ACAP and ACF
      at 1 year after KPT. CONCLUSIONS: KPT induces a significant improvement of
      neurophysiological signs of PNP and of ACF, which is statistically significant at
      1 year after KPT. In some patients, the improvement is heralded by an increase in
      the axonal damage, occurring in the first months after KPT, which may be due the
      aggression from the surgical treatment and related events.

PMID- 11988152
TI  - [Diagnostic value of D-dimer in patients with a low pretest probability of deep
      venous thrombosis of lower extremities].
AB  - BACKGROUND: We aimed to assess the accuracy of a diagnostic strategy including
      broth clinical assessment and determination of D-dimer (DD) in patients with
      clinically suspicion of low pretest probability of deep venous thrombosis (DVT).
      METHOD: 149 outpatients (mean age 69; SD 16) with clinically suspected proximal
      DVT attending our Emergency Department and classified as low pretest probability
      were included in an observational prospective study. In patients with a DD (STA
      Liatest D-Di, Diagnostica Stago, Asnieres sur Seine, France) concentration below
      the cut-off value (0.4 ng/ml) the diagnosis of DVT was readily ruled out, whereas
      those individuals with a positive DD result underwent compression Doppler venous
      ultrasound. A 3-month clinical follow-up was carried out in those patients in
      whom a diagnosis of DVT was initially excluded. RESULTS: Only 2 cases of DVT were
      confirmed (prevalence 1.3%; CI 95%, 0.2-5.3). In 47.6% of cases, a DD negativity
      ruled out the diagnosis of DVT. The rate of negative DD results was significantly
      lower in patients below 70 years of age as compared to older patients (73.6
      versus 33.3%) (p < 0.001). Sensitivity, specificity, positive predictive value
      and negative predictive value of DD in our series were 100% (CI 95%,19.7-95.1),
      48.3% (CI 95%, 40.0-56.7), 2.6% (CI 95%, 0.4-9.8) and 100% (CI 95%, 93.6-99.8)
      respectively, the latter being similar in the two age groups. No case of DVT was
      diagnosed during the follow-up period. CONCLUSIONS: In patients with a low
      pretest probability of DVT a negative DD result reliably and safely rules out
      such diagnosis. However, the diagnostic value of DD is lower in elderly patients
      (>= 70 years of age) due to a lower rate of negative results in these
      individuals.

PMID- 11988153
TI  - [Ambulatory monitoring of blood pressure during 24, 48, 72 hours. Which is the
      reasonable limit?].

PMID- 11988154
TI  - [Training of residents in Internal Medicine. Lessons from a survey].

PMID- 11988155
TI  - [Gastro-esophageal reflux disease].

PMID- 11988156
TI  - [Fatal poisoning and organ donation].

PMID- 11988158
TI  - [Niacin-induced hepatitis].

PMID- 11988159
TI  - [Bilateral facial paralysis as initial symptom in HIV infection].

PMID- 11988160
TI  - [Some reasons to screen diabetes mellitus in the elderly].

PMID- 11988161
TI  - And now, transcriptomics.
AB  - In this issue of Neuron, report different patterns of 5-HT2C pre-mRNA editing in
      suicide victims, as compared to controls. Treatment of mice with fluoxetine
      alters the pattern of 5-HT2C transcript editing in the direction opposite that
      observed for suicide victims. The authors speculate on a possible serotonergic
      mechanism controlling 5-HT2C pre-mRNA editing.

PMID- 11988162
TI  - Protein synthesis in the visual cortex is needed for ocular dominance plasticity.
AB  - Experience-dependent remodelling of neural connections progresses through stages,
      and early phases eventually give way to later long-lasting ones. The transition
      from early to late stages, often associated with structural changes, depends on
      protein synthesis. Suppression of cortical but not geniculate protein synthesis
      blocks ocular dominance plasticity at its earliest stage, suggesting that
      structural changes occur rapidly in the visual cortex following monocular
      deprivation.

PMID- 11988163
TI  - Depression at thalamocortical synapses: the key for cortical neuronal adaptation?
AB  - Neuronal adaptation to repetitive sensory stimuli is ubiquitous in the mammalian
      cortex. Despite its prevalence, the cellular mechanisms underlying this basic
      physiological property remain a matter of dispute. In this issue of Neuron, Chung
      et al. provide conclusive evidence that depression of thalamocortical synapses
      may play a significant role in the expression of neuronal adaptation in the rat
      somatosensory cortex.

PMID- 11988164
TI  - Knowing a nascent synapse when you see it.
AB  - To understand brain development, we must learn how synapse formation shapes
      functional neural circuits. At the heart of this process lies the nascent synapse
      -an enigmatic structure spanning the developmental gap between initial cell-cell
      contact and the mature synapse. New experimental techniques are beginning to
      illuminate the processes involved in synaptogenesis, but much remains to be
      learned, including simply how to recognize the synapse in its nascent form.

PMID- 11988165
TI  - Protons at the gate: DEG/ENaC ion channels help us feel and remember.
AB  - The DEG/ENaC ion channel family contributes to channels of striking functional
      diversity. Neuronally expressed family members include the C. elegans degenerins
      that mediate touch and are thought to be mechanically gated, and the mammalian
      ASICs, which are gated by protons. ASICs affect a range of sensory functions that
      includes perception of gentle touch, harsh touch, heat, sour taste, and pain.
      Family member ASIC1 is now implicated in long-term potentiation, suggesting that
      minute fluxes in synaptic pH may activate ASICs to enhance learning.

PMID- 11988166
TI  - Wiring optimization in cortical circuits.
AB  - Wiring a brain presents a formidable problem because neural circuits require an
      enormous number of fast and durable connections. We propose that evolution was
      likely to have optimized neural circuits to minimize conduction delays in axons,
      passive cable attenuation in dendrites, and the length of "wire" used to
      construct circuits, and to have maximized the density of synapses. Here we ask
      the question: "What fraction of the volume should be taken up by axons and
      dendrites (i.e., wire) when these variables are at their optimal values?" The
      biophysical properties of axons and dendrites dictate that wire should occupy 3/5
      of the volume in an optimally wired gray matter. We have measured the fraction of
      the volume occupied by each cellular component and find that the volume of wire
      is close to the predicted optimal value.

PMID- 11988167
TI  - Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of
      depressed suicide victims.
AB  - Five adenosines within the coding sequence of the serotonin 2C receptor (5-HT2C)
      pre-mRNA are converted to inosines by RNA editing (named A, B, C' (E), C, and D
      sites). In human prefrontal cortex (PFC), the most abundant 5-HT2C mRNA sequences
      result from editing at the A site, or from the editing combinations AC'C, ABCD,
      and ABD. In suicide victims with a history of major depression, C' site editing
      is significantly increased, D site editing is significantly decreased, and the C
      site shows a trend toward increased editing. Treatment of mice with the
      antidepressant drug fluoxetine (Prozac) causes changes in C', C, and D site
      editing that are exactly opposite to those seen in suicide victims. Thus, one
      outcome of fluoxetine treatment may be to reverse the abnormalities in 5-HT2C pre
      mRNA editing seen in depressed suicide victims.

PMID- 11988168
TI  - An intrinsic distinction in neuromuscular junction assembly and maintenance in
      different skeletal muscles.
AB  - We analyzed the formation of neuromuscular junctions (NMJs) in individual muscles
      of the mouse embryo. Skeletal muscles can be assigned to one of two distinct
      classes of muscles, termed "Fast Synapsing" (FaSyn) and "Delayed Synapsing"
      (DeSyn) muscles, which differ significantly with respect to the initial focal
      clustering of postsynaptic AChRs, the timing of presynaptic maturation, and the
      maintenance of NMJs in young adult mice. Differences between classes were
      intrinsic to the muscles and manifested in the absence of innervation or agrin.
      Paralysis or denervation of young adult muscles resulted in disassembly of AChR
      clusters on DeSyn muscles, whereas those on FaSyn muscles were preserved. Our
      results show that postsynaptic differentiation processes intrinsic to FaSyn and
      DeSyn muscles influence the formation of NMJs during development and their
      maintenance in the adult.

PMID- 11988169
TI  - Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice
      lacking CREB.
AB  - CRE-binding protein (CREB) belongs to a family of transcription factors that
      mediates stimulus-dependent gene expression in neuronal and non-neuronal cells.
      Here we show that CREB is phosphorylated on its transcriptional regulatory site,
      Ser-133, in vivo in a neurotrophin-dependent manner. In mice harboring a null
      mutation in the Creb gene, sensory neurons exhibit excess apoptosis and
      degeneration, and display impaired axonal growth and projections. Interestingly,
      excess apoptosis is not observed in the central nervous system. CREB is required
      within sensory and sympathetic neurons for survival and axon extension since both
      of these neurotrophin-dependent processes are compromised in cultured neurons
      from CREB null mice. Thus, during their period of neurotrophin dependency,
      peripheral neurons require CREB-mediated gene expression for both survival and
      growth in vivo.

PMID- 11988170
TI  - PSD-95 mediates formation of a functional homomeric Kir5.1 channel in the brain.
AB  - Homomeric assembly of Kir5.1, an inward-rectifying K+ channel subunit, is
      believed to be nonfunctional, although the subunit exists abundantly in the
      brain. We show that HEK293T cells cotransfected with Kir5.1 and PSD-95 exhibit a
      Ba(2+)-sensitive inward-rectifying K+ current. Kir5.1 coexpressed with PSD-95
      located on the plasma membrane in a clustered manner, while the Kir5.1 subunit
      expressed alone distributed mostly in cytoplasm, probably due to rapid
      internalization. The binding of Kir5.1 with PSD-95 was prevented by protein
      kinase A (PKA)-mediated phosphorylation of its carboxyl terminus. The currents
      flowing through Kir5.1/PSD-95 were suppressed promptly and reversibly by PKA
      activation. Because the Kir5.1/PSD-95 complex was detected in the brain, this
      functional brain K+ channel is potentially a novel physiological target of PKA
      mediated signaling.

PMID- 11988171
TI  - The sigma receptor as a ligand-regulated auxiliary potassium channel subunit.
AB  - The sigma receptor is a novel protein that mediates the modulation of ion
      channels by psychotropic drugs through a unique transduction mechanism depending
      neither on G proteins nor protein phosphorylation. The present study investigated
      sigma receptor signal transduction by reconstituting responses in Xenopus
      oocytes. Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in
      different ways in the presence and absence of ligands. Association between Kv1.4
      channels and sigma receptors was demonstrated by coimmunoprecipitation. These
      results indicate a novel mechanism of signal transduction dependent on protein
      protein interactions. Domain accessibility experiments suggested a structure for
      the sigma receptor with two cytoplasmic termini and two membrane-spanning
      segments. The ligand-independent effects on channels suggest that sigma receptors
      serve as auxiliary subunits to voltage-gated K+ channels with distinct functional
      interactions, depending on the presence or absence of ligand.

PMID- 11988172
TI  - RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage
      gated Ca(2+) channels.
AB  - Ca(2+) influx through voltage-gated channels initiates the exocytotic fusion of
      synaptic vesicles to the plasma membrane. Here we show that RIM binding proteins
      (RBPs), which associate with Ca(2+) channels in hair cells, photoreceptors, and
      neurons, interact with alpha(1D) (L type) and alpha(1B) (N type) Ca(2+) channel
      subunits. RBPs contain three Src homology 3 domains that bind to proline-rich
      motifs in alpha(1) subunits and Rab3-interacting molecules (RIMs). Overexpression
      in PC12 cells of fusion proteins that suppress the interactions of RBPs with RIMs
      and alpha(1) augments the exocytosis triggered by depolarization. RBPs may
      regulate the strength of synaptic transmission by creating a functional link
      between the synaptic-vesicle tethering apparatus, which includes RIMs and Rab3,
      and the fusion machinery, which includes Ca(2+) channels and the SNARE complex.

PMID- 11988173
TI  - Rapid ocular dominance plasticity requires cortical but not geniculate protein
      synthesis.
AB  - Synaptic plasticity is a multistep process in which rapid, early phases
      eventually give way to slower, more enduring stages. Diverse forms of synaptic
      change share a common requirement for protein synthesis in the late stages of
      plasticity, which are often associated with structural rearrangements. Ocular
      dominance plasticity in the primary visual cortex (V1) is a long-lasting form of
      activity-dependent plasticity comprised of well-defined physiological and
      anatomical stages. The molecular events underlying these stages remain poorly
      understood. Using the protein synthesis inhibitor cycloheximide, we investigated
      a role for protein synthesis in ocular dominance plasticity. Suppression of
      cortical, but not geniculate, protein synthesis impaired rapid ocular dominance
      plasticity, while leaving neuronal responsiveness intact. These findings suggest
      that structural changes underlying ocular dominance plasticity occur rapidly
      following monocular occlusion, and cortical changes guide subsequent alterations
      in thalamocortical afferents.

PMID- 11988174
TI  - Short-term depression at thalamocortical synapses contributes to rapid adaptation
      of cortical sensory responses in vivo.
AB  - In vivo whole-cell recordings revealed that during repeated stimulation, synaptic
      responses to deflection of facial whiskers rapidly adapt. Extracellular
      recordings in the somatosensory thalamus revealed that part of the adaptation
      occurs subcortically, but because cortical adaptation is stronger and recovers
      more slowly, cortical mechanisms must also contribute. Trains of sensory stimuli
      that produce profound sensory adaptation did not alter intrinsic membrane
      properties, including resting membrane potential, input resistance, and current
      evoked firing. Synaptic input evoked via intracortical stimulation was also
      unchanged; however, synaptic input from the somatosensory thalamus was depressed
      by sensory stimulation, and this depression recovered with a time course matching
      that of the recovery of sensory responsiveness. These data strongly suggest that
      synaptic depression of thalamic input to the cortex contributes to the dynamic
      regulation of neuronal sensitivity during rapid changes in sensory input.

PMID- 11988175
TI  - Reversible inhibition of CREB/ATF transcription factors in region CA1 of the
      dorsal hippocampus disrupts hippocampus-dependent spatial memory.
AB  - CREB is critical for long-lasting synaptic and behavioral plasticity in
      invertebrates. Its role in the mammalian hippocampus is less clear. We have
      interfered with CREB family transcription factors in region CA1 of the dorsal
      hippocampus. This impairs learning in the Morris water maze, which specifically
      requires the dorsal hippocampus, but not context conditioning, which does not.
      The deficit is specific to long-term memory, as shown in an object recognition
      task. Several forms of late-phase LTP are normal, but forskolin-induced and
      dopamine-regulated potentiation are disrupted. These experiments represent the
      first targeting of the dorsal hippocampus in genetically modified mice and
      confirm a role for CREB in hippocampus-dependent learning. Nevertheless, they
      suggest that some experimental forms of plasticity bypass the requirement for
      CREB.

PMID- 11988177
TI  - Eccentricity bias as an organizing principle for human high-order object areas.
AB  - We have recently proposed a center-periphery organization based on resolution
      needs, in which objects engaging in recognition processes requiring central
      vision (e.g., face-related) are associated with center-biased representations,
      while objects requiring large-scale feature integration (e.g., buildings) are
      associated with periphery-biased representations. Here we tested this hypothesis
      by comparing the center-periphery organization with activations to five object
      categories: faces, buildings, tools, letter strings, and words. We found that
      faces, letter strings, and words were mapped preferentially within the center
      biased representation. Faces showed a hemispheric lateralization opposite to that
      of letter strings and words. In contrast, buildings were mapped mainly to the
      periphery-biased representation, while tools activated both central and
      peripheral representations. The results are compatible with the notion that
      center-periphery organization allows the optimal allocation of cortical
      magnification to the specific requirements of various recognition processes.

PMID- 11988176
TI  - The acid-activated ion channel ASIC contributes to synaptic plasticity, learning,
      and memory.
AB  - Many central neurons possess large acid-activated currents, yet their molecular
      identity is unknown. We found that eliminating the acid sensing ion channel
      (ASIC) abolished H(+)-gated currents in hippocampal neurons. Neuronal H(+)-gated
      currents and transient acidification are proposed to play a role in synaptic
      transmission. Investigating this possibility, we found ASIC in hippocampus, in
      synaptosomes, and in dendrites localized at synapses. Moreover, loss of ASIC
      impaired hippocampal long-term potentiation. ASIC null mice had reduced
      excitatory postsynaptic potentials and NMDA receptor activation during high
      frequency stimulation. Consistent with these findings, null mice displayed
      defective spatial learning and eyeblink conditioning. These results identify ASIC
      as a key component of acid-activated currents and implicate these currents in
      processes underlying synaptic plasticity, learning, and memory.

PMID- 11988178
TI  - Flexoelectricity of model and living membranes.
AB  - The theory and experiments on model and biomembrane flexoelectricity are
      reviewed. Biological implications of flexoelectricity are underlined. Molecular
      machinery and molecular electronics applications are pointed out.

PMID- 11988179
TI  - Viral ion channels: structure and function.
AB  - Viral ion channels are short auxiliary membrane proteins with a length of ca. 100
      amino acids. They are found in enveloped viruses from influenza A, influenza B
      and influenza C (Orthomyxoviridae), and the human immunodeficiency virus type 1
      (HIV-1, Retroviridae). The channels are called M2 (influenza A), NB (influenza
      B), CM2 (influenza C) and Vpu (HIV-1). Recently, in Paramecium bursaria chlorella
      virus (PBCV-1, Phycodnaviridae), a K+ selective ion channel has been discovered.
      The viral channels form homo oligomers to allow an ion flux and represent
      miniaturised systems. Proton conductivity of M2 is established; NB, Vpu and the
      potassium channel from PBC-1 conduct ions; for CM2 ion conductivity is still
      under proof. This review summarises the current knowledge of these short viral
      membrane proteins. Their discovery is outlined and experimental evidence for
      their structure and function is discussed. Studies using computational methods
      are presented as well as investigations of drug-protein interactions.

PMID- 11988180
TI  - Structure and association of ATP-binding cassette transporter nucleotide-binding
      domains.
AB  - ATP-binding cassette transporters are responsible for the uptake and efflux of a
      multitude of substances across both eukaryotic and prokaryotic membranes. Members
      of this family of proteins are involved in diverse physiological processes
      including antigen presentation, drug efflux from cancer cells, bacterial nutrient
      uptake and cystic fibrosis. In order to understand more completely the role of
      these multidomain transporters an integrated approach combining structural,
      pharmacological and biochemical methods is being adopted. Recent structural data
      have been obtained on the cytoplasmic, nucleotide-binding domains of prokaryotic
      ABC transporters. This review evaluates both these data and the conflicting
      implications they have for domain communication in ABC transporters. Areas of
      biochemical research that attempt to resolve these conflicts will be discussed.

PMID- 11988181
TI  - Fluorescent probes for monitoring virus fusion kinetics: comparative evaluation
      of reliability.
AB  - Fluorescence assays for viral membrane fusion employ lipidic probes whose
      kinetics of fluorescence dequenching should mimic the actual kinetics of membrane
      merging. We examined the fusion of influenza virus with CEM cells, erythrocyte
      ghosts or liposomes by monitoring the fluorescence dequenching of each one of the
      three probes, octadecylrhodamine B chloride (R18), N-(lissamine rhodamine B
      sulfonyl)phosphatidylethanolamine (Rh-PE), or rac-2,3-dioleoylglycerol ester of
      rhodamine B (DORh-B), inserted into the virus membrane. Experimental conditions
      were designed to allow a clear distinction between membrane mixing and non
      specific probe transfer. Fluorescence dequenching observed with Rh-PE was much
      slower than with R18, unless a particular experimental procedure was used. Using
      liposomes as a target membrane, the kinetics and extent of the decrease in
      resonance energy transfer between N-(7-nitro-2,1,3-benzoxadiazol-4
      yl)phosphatidylethanolamine (NBD-PE) and Rh-PE, initially embedded in the
      liposome membrane, were matched by that of the dequenching of viral R18, but not
      of viral Rh-PE. DORh-B was found not to be appropriate to follow membrane
      merging. Our results indicate that on a time scale of several minutes R18 more
      accurately reflects the kinetics of membrane fusion. Nevertheless, control
      experiments should be performed to evaluate non-specific probe transfer of R18
      molecules, whose contribution to fluorescence dequenching can become significant
      after long incubation times.

PMID- 11988182
TI  - Synaptotagmin I-DeltaC2B. A novel synaptotagmin isoform with a single C2 domain
      in the bovine adrenal medulla.
AB  - Synaptotagmin I is a 65 kDa type 1 membrane glycoprotein found in secretory
      organelles that plays a key role in regulated exocytosis. We have characterised
      two forms (long and short) of synaptotagmin I that are present in the bovine
      adrenal medulla. The long form is a type I integral membrane protein which has
      two cytoplasmic C2 domains and corresponds to the previously characterised full
      length synaptotagmin I isoform. The short-form synaptotagmin I-DeltaC2B has the
      same structure in the lumenal and transmembrane sequences, but synaptotagmin I
      DeltaC2B is truncated such that it only has a single cytoplasmic C2 domain.
      Analysis of synaptotagmin I-DeltaC2B expression indicates that synaptotagmin I
      DeltaC2B is preferentially expressed in the bovine adrenal medulla. However, it
      is absent from the dense core chromaffin granules. Furthermore, when expressed in
      the rat pheochromocytoma cell line PC12 bovine synaptotagmin I-DeltaC2B is
      largely absent from dense core granules and synaptic-like microvesicles. Instead,
      indirect immunofluorescence microscopy reveals the intracellular location of
      synaptotagmin I-DeltaC2B to be the plasma membrane.

PMID- 11988183
TI  - Biodistribution of long-circulating PEG-liposomes in a murine model of
      established subcutaneous abscesses.
AB  - The biodistribution of long-circulating PEG-liposomes in a subcutaneous mouse
      model of established mixed infection abscesses was investigated to assess their
      possible role as drug carriers in the treatment of small, undrainable intra
      abdominal abscesses. There was a 10-30-fold greater localisation of (67)Ga
      labelled PEG-liposomes in abscesses compared to uninfected normal skin samples.
      Over 3% of the injected dose (ID) of liposomes was present in the abscesses 24 h
      after liposome administration in contrast to 0.1% in normal skin sections. The
      percentage ID present in the liver, spleen and kidneys was 17%, 4% and 2% per
      organ respectively. Five days after liposome injection, 2% ID could still be
      recovered from the abscesses. Using colloidal gold-labelled PEG-liposomes, it was
      shown that there was a 4-fold greater density of liposome clusters in the
      subcutaneous tissue surrounding the capsule than in the core of the abscesses.
      The clusters within the abscesses were distributed evenly. We conclude that PEG
      liposomes localise to a significant degree at the infection focus in our mouse
      model and may provide a new approach to the antimicrobial treatment of intra
      abdominal abscesses.

PMID- 11988184
TI  - Two functionally distinct organic osmolyte pathways in Plasmodium gallinaceum
      infected chicken red blood cells.
AB  - Red cells infected with the human malaria parasite Plasmodium falciparum have an
      increased permeability to a range of small, structurally unrelated solutes via a
      malaria-induced pathway. We report here a similar pathway present in parasitised
      red cells from chickens infected with the avian malaria parasite, Plasmodium
      gallinaceum. Parasitised cells showed a marked increase in the rate of influx of
      sorbitol (76-fold) and, to a lesser degree, taurine (3-fold) when compared with
      red cells from uninfected chickens. Pharmacological data suggest that both
      sorbitol and taurine are transported via a single malaria-induced pathway, which
      is sensitive to inhibition by 5-nitro-2-(3-phenylpropylamino)benzoic acid (IC(50)
      approximately 7 microM). The malaria-induced pathway differed in its inhibition
      by a range of anion channel inhibitors when compared to the endogenous, volume
      activated osmolyte pathway of chicken red cells. There were also differences in
      the selectivity of sorbitol and taurine by the two permeation routes. The data
      presented here are consistent with the presence of two distinct organic solute
      pathways in infected chicken red cells. The first is an endogenous volume
      activated pathway, which is not activated by the parasite and the second is a
      malaria-induced pathway, similar to those that are induced by other types of
      malaria in other host species.

PMID- 11988185
TI  - Differential destabilization of membranes by tryptophan and phenylalanine during
      freezing: the roles of lipid composition and membrane fusion.
AB  - The stability of cellular membranes during dehydration can be strongly influenced
      by the partitioning of amphiphilic solutes from the aqueous phase into the
      membranes. The effects of partitioning on membrane stability depend in a complex
      manner on the structural properties of the amphiphiles and on membrane lipid
      composition. Here, we have investigated the effects of the amphiphilic aromatic
      amino acids Trp and Phe on membrane stability during freezing. Both amino acids
      were cryotoxic to isolated chloroplast thylakoid membranes and to large
      unilamellar liposomes, but Trp had a much stronger effect than Phe. In liposomes,
      both amino acids induced solute leakage and membrane fusion during freezing. The
      presence of the chloroplast galactolipids monogalactosyldiacylglycerol or
      digalactosyldiacylglycerol in egg phosphatidylcholine (EPC) membranes reduced
      leakage from liposomes during freezing in the presence of up to 5 mM Trp, as
      compared to membranes composed of pure EPC. The presence of the nonbilayer
      forming lipid phosphatidylethanolamine increased leakage. Membrane fusion
      followed a similar trend, but was dramatically reduced when the anthracycline
      antibiotic daunomycin was incorporated into the membranes. Daunomycin has been
      shown to stabilize the bilayer phase of membranes in the presence of nonbilayer
      lipids and was therefore expected to reduce fusion. Surprisingly, this had only a
      small influence on leakage. Collectively, these data indicate that Trp and Phe
      induce solute leakage from liposomes during freezing by a mechanism that is
      largely independent of fusion events.

PMID- 11988186
TI  - The effect of fusion inhibitors on the phase behaviour of N-methylated
      dioleoylphosphatidylethanolamine.
AB  - The effects of two fusion inhibitors on the lipid polymorphism of N-methylated
      dioleoylphosphatidylethanolamine were studied using temperature-resolved, small
      angle X-ray diffraction. The inhibitory role of the tri-peptide carbobenzoxy-D
      phenylalanine-L-phenylalanine-glycine and the lipid 1-lauroyl-2-hydroxy-sn
      glycero-3-phosphocholine in the fusion pathway was studied, using the non
      lamellar phase behaviour of the lipid as a model. We used p15EK, the N-terminal
      region of gp41 from feline leukaemia virus as promoter of membrane fusion, and
      measured the structural parameters of each observed lipid phase as a function of
      temperature. The fusion inhibitors were found to impede the expression of
      negative curvature of lipid monolayers even in the presence of fusion peptide.
      The results of this study are interpreted in relation to models of the membrane
      fusion mechanism.

PMID- 11988187
TI  - Usefulness of QRS duration in the absence of bundle branch block as an early
      predictor of survival in non-ST elevation acute myocardial infarction.
AB  - To determine whether an increased QRS duration in the absence of bundle branch
      block (BBB) on the presenting electrocardiogram of patients with acute myocardial
      infarction (AMI) is associated with decreased survival, we retrospectively
      reviewed 781 consecutive patients admitted to the coronary care unit of our
      institution with AMI without BBB between 1988 and 1998. In patients with ST
      elevation AMI (n = 412), the groups with QRS duration > or =100 ms and <100 ms
      had similar survival. Conversely, in patients with non-ST elevation AMI (n =
      369), in-hospital, 1-, 3-, and 5-year survival was 84.4%, 75.6%, 66.7%, and
      52.2%, respectively, in the group with QRS > or =100 ms compared with 95.4%,
      89.2%, 83.8%, and 74.3%, respectively, in the group with QRS <100 ms (p <0.01,
      log-rank test). In patients with non-ST elevation AMI, those with QRS duration >
      or =100 ms were more likely to be men, to have had a prior AMI that healed, to be
      in Killip class II, III, or IV, and to have lower ejection fraction than patients
      with QRS duration <100 ms. After adjusting for age, sex, prior AMI or stroke,
      heart rate, and Killip class on admission, QRS duration > or =100 ms was
      independently associated with in-hospital and overall mortality in patients with
      non-ST elevation AMI. QRS duration > or =100 ms in the absence of BBB is an
      independent predictor of increased mortality in patients with non-ST elevation
      AMI.

PMID- 11988188
TI  - Effect of oral nitroglycerin and cold stress on myocardial perfusion in areas
      subtended by stenosed and nonstenosed coronary arteries.
AB  - Physical obstruction and coronary vasoconstriction mediated by adrenergic stress
      are believed to be responsible for episodes of myocardial hypoperfusion and
      angina. Nitroglycerin relieves symptoms by reducing preload and dilating
      epicardial vessels. The net perfusion change and relation to stenosis severity of
      nitroglycerin and adrenergic stress have been debated. This study aimed to
      evaluate whether oral nitroglycerin and adrenergic stress alters perfusion in
      myocardial segments subtended by stenosed and nonstenosed coronary arteries.
      Myocardial perfusion was quantified (using N-13-ammonia positron emission
      tomography [PET]) at rest, after oral nitroglycerin 400 microg, and after cold
      stress in 25 patients with coronary artery disease (62 +/- 9 years, 21 men) and
      in 30 controls (34 +/- 9 years, 22 men). Myocardial perfusion was quantified in
      areas supplied by stenosed (>70%) and nonstenosed (<30%) coronary arteries. The
      cold pressor test did not significantly alter myocardial perfusion in any of the
      groups. However, when normalized for rate-pressure product, the response in
      stenosed areas showed a significantly more pronounced reduction compared with
      nonstenosed areas (0.78 +/- 0.18 vs 0.64 +/- 0.19 ml/g/min, p <0.005 and 0.86 +/-
      0.19 vs 0.73 +/- 0.24 ml/g/min, p <0.05, p <0.05) for intergroup comparison. In
      both stenosed areas and nonstenosed areas nitroglycerin increased perfusion (0.51
      +/- 0.14 vs 0.60 +/- 0.17 ml/g/min, p <0.05 and 0.56 +/- 0.14 vs 0.61 +/- 0.17
      ml/g/min, p <0.05). Nitroglycerin did not alter myocardial perfusion in the
      control group. There was a negative correlation between the cold pressor test
      response and stenosis severity (r(2) = 0.17, p <0.046), whereas this was not the
      case for nitroglycerin. In patients with coronary artery disease, myocardial
      segments supplied by stenosed coronary arteries showed an altered perfusion
      response to adrenergic stress. Oral nitroglycerin increased myocardial perfusion
      irrespective of the presence of a stenosis.

PMID- 11988189
TI  - Association of wall thickness of the brachial artery measured with high
      resolution ultrasound with risk factors and coronary artery disease.
AB  - Intima-media thickness of the carotid and femoral arteries has been associated
      with coronary atherosclerosis and its clinical sequelae. The brachial artery (BA)
      is widely used for the assessment of flow-mediated vasodilation. The aim of this
      study was to examine whether BA wall thickness (WT) is associated with coronary
      artery disease (CAD) and risk factors. High-resolution ultrasound (13 MHz)
      examination of the BA was performed in 179 patients undergoing coronary
      angiography for the evaluation of chest pain. CAD (> or =30% diameter stenosis in
      > or =1 major branch) was found in 132 patients, whereas 47 patients had smooth
      coronary arteries. WT of the posterior BA wall (0.4 +/- 0.05 vs 0.35 +/- 0.06 mm,
      p <0.001) and wall index (WI) (WT/vessel diameter x 100; 16.1 +/- 0.0 vs 13.8 +/-
      0.8, p <0.001) were greater in patients with than without CAD. On univariate
      analysis, WT and WI correlated with age, presence of CAD, systemic hypertension,
      maximum coronary diameter stenosis, and baseline diameter. On logistic regression
      analyses adjusting for age, cholesterol levels, systemic hypertension, smoking,
      and positive family history, WT (p <0.01) and WI (p = 0.02) remained
      significantly correlated with the presence of CAD. Thus, BA-WT is independently
      correlated with the presence of CAD. WT may provide a novel noninvasive marker of
      atherosclerosis that can be assessed together with flow-mediated vasodilation to
      yield functional and morphologic information in the same vessel.

PMID- 11988190
TI  - Aortic valve sclerosis, mitral annular calcium, and aortic root sclerosis as
      markers of atherosclerosis in men.
AB  - Aortic valve sclerosis (AVS) and mitral annular calcium (MAC) as detected by
      transthoracic echocardiography have been associated with atherosclerosis. Aortic
      root sclerosis (ARS) may have a similar association, but has not been studied.
      This study evaluates, by transesophageal echocardiography, the association of
      AVS, MAC, and ARS with aortic atheromatous disease and cardiovascular disease.
      Multiplane transesophageal echocardiography with evaluation of AVS, MAC, ARS, and
      aortic atheromatous disease by 2 experienced observers unaware of clinical data
      was performed in 157 male patients > or =50 years old. The presence of
      cardiovascular disease, defined as coronary, carotid, or peripheral artery
      disease, was determined by specific criteria. The prevalence of AVS, MAC, ARS,
      and aortic atheromatous disease was 42%, 30%, 48%, and 71%, respectively. The
      presence of AVS, MAC, or ARS was highly associated with aortic atheromatous
      disease (odds ratio 4.9 to 12.0, confidence interval 1.4 to 35.8, p <0.001). ARS
      was also associated with cardiovascular disease (odds ratio 2.2, confidence
      interval 1.0 to 4.5, p = 0.038). The presence of AVS, MAC, or ARS had a
      sensitivity of 77%, specificity of 72%, a positive predictive value of 88%, and a
      negative predictive value of 55% for aortic atheromatous disease. We concluded
      that the prevalence of AVS, MAC, or ARS by transesophageal echocardiography in
      men is common, and their presence is highly associated with aortic atheromatous
      disease and coronary, carotid, or peripheral artery disease.

PMID- 11988191
TI  - Clinical performance of three cardiac troponin assays in patients with unstable
      coronary artery disease (a FRISC II substudy).
AB  - The assay of cardiac-specific troponins (cTroponins) is a sensitive and specific
      means to diagnose myocardial injury. Several assays for the measurement of
      cardiac-specific troponin I (cTnI), but only 1 for the assay of cardiac specific
      troponin T (cTnT), are commercially available. The aim of this study was to
      compare 3 of these assays (i.e., Access AccuTnI [cTnI], AxSym [cTnI], and Elecsys
      3(rd) generation [cTnI]) and their clinical performances in a group of patients
      (n = 1,763) with unstable coronary artery disease (Fragmin and fast
      Revascularisation during InStability in Coronary artery disease [FRISC II]
      trial). Clinical events after 1-year follow-up, such as death and death and/or
      acute myocardial infarction, were recorded and the effects of invasive or
      noninvasive treatment evaluated in relation to cTroponin levels. Overall the 2
      cTnI methods showed good correlation (r(s) = 0.96), whereas correlations to the
      cTnT assay were somewhat lower (r(s) = 0.93). Patients with nonelevated levels,
      as measured with any of the 3 biomarkers, had a significantly better prognosis
      than patients with elevated levels (p <0.001). A cohort of 10% to 12.4% of
      patients with a poor prognosis was identified only by the Access AccuTnI assay.
      Invasive treatment reduced clinical events only in the group of patients with
      elevated cTroponin levels. We conclude that stratification of patients with
      unstable coronary artery disease by means of cTroponin measurements is important
      in clinical management. It is also apparent that assays with superior
      sensitivity, such as the Access AccuTnI, identify more patients with poor
      prognosis who are candidates for early invasive procedures.

PMID- 11988192
TI  - Patient-reported frequency of taking aspirin in a population with coronary artery
      disease.
AB  - Despite the established benefits of antiplatelet agents in coronary artery
      disease (CAD), many appropriate patients are not receiving them. We investigated
      the prevalence of and factors associated with aspirin use and nonuse within a
      large referral population with CAD. The goal was to identify an approach to
      increase the use of antiplatelet agents by such patients. We surveyed a subset (n
      = 2,694) of a large CAD referral population (n = 16,174) to determine the use of
      aspirin and factors associated with its use or nonuse. The subset was made up of
      all of the CAD referral population who were considered nonusers of aspirin and a
      5% sample of those considered aspirin users. We then extrapolated survey data to
      the overall population to estimate how many eligible patients were not taking
      antiplatelet agents. In all, 1,626 (63%) of the surviving patients responded to
      the survey. Of these, 948 (58%) reported taking aspirin, and 678 (42%) reported
      no aspirin use. The extrapolated rate of aspirin use in the overall population
      was 85%. Of 2,367 nonusers, 998 (42%, or 6% of the overall cohort) were eligible
      for antiplatelet agents but were not taking such therapy. Although the rate of
      aspirin use in this population was higher than previously reported, an estimated
      6% of eligible patients were not receiving antiplatelet therapy.

PMID- 11988193
TI  - Effects of resynchronization therapy on sympathetic activity in patients with
      depressed ejection fraction and intraventricular conduction delay due to ischemic
      or idiopathic dilated cardiomyopathy.
AB  - This study assesses the effect of biventricular pacing on sympathetic nerve
      activity (SNA) in patients with depressed ejection fraction and intraventricular
      conduction delay (IVCD). Biventricular pacing has been shown to result in
      hemodynamic improvement in patients with depressed ejection fraction and IVCD.
      The effect of biventricular pacing on SNA, however, remains unclear. A total of
      15 men with a mean ejection fraction of 25 +/- 4% were enrolled. Arterial
      pressure, central venous pressure and SNA were recorded during 3 minutes of right
      atrial (RA) pacing and RA-biventricular pacing. Pacing was performed at a rate 5
      to 10 beats faster than sinus rhythm, with an atrioventricular interval equal to
      100 ms during RA-biventricular pacing. RA-biventricular pacing resulted in
      greater arterial pressures (p <0.05) than RA pacing (146 +/- 15/83 +/- 11 vs 141
      +/- 15/80 +/- 10 mm Hg). There were no differences in central venous pressures
      between the 2 pacing modes (p = 0.76). SNA was significantly less during RA
      biventricular pacing (727 +/- 242 U) than during RA pacing (833 +/- 332 U) (p
      <0.02). Furthermore, there was a positive correlation between baseline QRS
      duration and the decrease in SNA noted with RA-biventricular pacing (r = 0.58, p
      = 0.03). Biventricular pacing results in improved hemodynamics and a decrease in
      SNA compared with intrinsic conduction in patients with left ventricular
      dysfunction and IVCD. If the current findings are also present with chronic
      biventricular pacing, then this form of therapy may have a positive impact on
      mortality.

PMID- 11988194
TI  - Gender difference in diastolic function in hypertension (the HyperGEN study).
AB  - Although several studies indicate that there are gender differences in left
      ventricular (LV) systolic function, it remains unclear whether similar
      differences exist with regard to diastolic function. Accordingly, Doppler
      echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%)
      hypertensive participants enrolled in the Hypertension Genetic Epidemiology
      Network (HyperGEN) study with no evidence of abnormal wall motion or significant
      valvular heart disease. There was no difference in age between genders, but after
      adjusting for age and race, men had lower body mass indexes (29.8 +/- 5.2 vs 32.3
      +/- 7.6 kg/m(2)) and heart rates (67 +/- 12 vs 69 +/- 11 beats/min) and higher
      systolic and diastolic blood pressures (BP) than women (134 +/- 20 vs 130 +/- 21
      and 80 +/- 11 vs 72 +/- 11 mm Hg, all p <0.001). LV mass/height(2.7) was slightly
      greater in women than in men (43 +/- 10 vs 42 +/- 9 g/m(2.7), p <0.05). After
      adjusting for age, race, systolic BP, body mass index, heart rate, and LV
      hypertrophy, both mitral E-wave (70 +/- 18 vs 77 +/- 19) and A-wave (74 +/- 15 vs
      79 +/- 17, both p <0.001) velocities were lower in men than in women, but the
      mitral E/A ratio and atrial filling fraction were nearly identical in both
      genders. Deceleration time (221 +/- 55 vs 214 +/- 46 cm/s, p = 0.018) and
      isovolumic relaxation time (IVRT) were longer in men than in women (85 +/- 18 vs
      81 +/- 17 cm/s, p <0.001). Prolonged IVRT was present in more men than women (14%
      vs 7%, p <0.05). In analyses of covariance, adjusting for age, race, systolic BP,
      body mass index, heart rate, and medications, male gender remained related to
      prolonged deceleration time and IVRT. Thus, in this population-based sample of
      hypertensive adults, men had evidence of slower early diastolic LV filling than
      women. This gender difference in diastolic function may provide insight into
      gender differences in congestive heart failure and other specific cardiovascular
      diseases.

PMID- 11988195
TI  - Relation of "inotropic reserve" to functional capacity in heart failure secondary
      to ischemic or nonischemic cardiomyopathy.
AB  - Exercise capacity in patients with dilated cardiomyopathy, measured by peak
      oxygen consumption (VO(2)) during exercise, has virtually no relation to resting
      left ventricular (LV) function. We hypothesized that exercise-induced inotropic
      reserve may explain some of the variation between peak VO(2) and resting LV
      function. Treadmill stress echocardiography was performed simultaneously with
      peak VO(2) measurements in 35 patients with dilated cardiomyopathy. Resting and
      immediate postexercise echocardiographic images were scored for change in
      segmental contractility using the American Society of Echocardiography 16-segment
      system. Segment scores were summed and divided by 16 to determine the wall motion
      index. Right ventricular (RV) function was quantified on a 4-point scale.
      Patients had a mean age of 52 +/- 12 years (8 women) and a mean ejection fraction
      of 30 +/- 10 (25 nonischemic patients). Average peak VO(2) was 17.0 +/- 6
      ml/kg/min. Patients were divided into 2 groups by peak VO(2): a high VO(2) group,
      >17 ml/kg/min (17 patients) and a low VO(2) group, < or =17 ml/kg/min (18
      patients). LV ejection fraction was similar between the high and low VO(2) groups
      (31 +/- 9% vs 28 +/- 11%, p = NS) as were etiology of heart failure, medications
      used, and LV volume. In the high VO(2) group, wall motion index improved from
      2.28 +/- 0.20 to 2.12 +/- 0.31 during exercise (p = 0.009). There was no
      improvement in the low VO(2) group. Resting RV function was significantly better
      in the high VO(2) group (1.4 +/- 0.8 vs 0.6 +/- 0.6 p = 0.004). Therefore, in
      patients with dilated cardiomyopathy and similar resting LV function, the
      presence of demonstrable LV inotropic reserve and preserved RV function partially
      account for variation in exercise performance.

PMID- 11988196
TI  - Frequency, predictors, and consequences of atrioventricular block after mitral
      valve repair.
AB  - This study examines the incidence, predictors, and evolution of postoperative
      atrioventricular block (AVB) after mitral valve repair (MVR) in 115 consecutive
      patients using Carpentier's technique (between November 1996 and April 1997).
      Postoperative AVB occurred in 27 patients (23%). Third-degree AVB was found in 7
      patients (6%) in the immediate postoperative period, but in 4 it was transient,
      resolving partially or completely before the seventh postoperative day. Second
      degree AVB (Mobitz type I) occurred in 4 patients (3%) immediately after
      operation and resolved in all before hospital discharge. Isolated first-degree
      AVB occurred in 16 patients (14%) and was permanent in 12. Neither the
      preoperative variables nor the mitral procedures including anterior versus
      posterior leaflet repair were related to postoperative AVB. A lesser systemic
      hypothermia during surgery was the only, modestly independent predictor of
      postoperative AVB (odds ratio 1.53; 95% confidence interval 1.04 to 2.25; p =
      0.031). Three patients (2.6%) had permanent pacemaker implantation, on average 18
      days after operation, and all had persistent third-degree AVB. With a mean follow
      up of 3 years, no recurrence or worsening of conduction disturbances, no further
      pacemaker implantation, and no late deaths were observed.

PMID- 11988197
TI  - Usefulness of pulsed tissue Doppler imaging for evaluating systolic and diastolic
      left ventricular function in patients with AL (primary) amyloidosis.
AB  - To clarify whether pulsed tissue Doppler imaging at multiple left ventricular LV
      sites could help to explain the mechanism of congestive heart failure (CHF) in
      patients with primary amyloidosis, we examined 86 consecutive patients with
      primary amyloidosis confirmed by biopsy (group I, 31 patients without cardiac
      involvement; group II, 31 patients with evidence of heart involvement but no CHF;
      and group III, 24 patients with heart involvement, clinical CHF, and normal
      fractional shortening >28%). Peak early diastolic myocardial velocities in group
      II were significantly lower than those in group I, and the values in group III
      were also significantly lower than those in group II at most sites. In contrast
      to diastolic abnormalities, peak systolic wall motion velocities in group III
      were significantly lower than those in group II, but there were no significant
      differences between groups I and II. Thus, cardiac amyloidosis is characterized
      by an initial impairment in early cardiac relaxation, whereas CHF is associated
      with an impairment of peak systolic wall motion velocities, most prominently seen
      in the longitudinal axis. This systolic dysfunction can be detected by pulsed
      tissue Doppler imaging, even when ejection fraction is in the normal range.

PMID- 11988198
TI  - Predictors of appropriate implantable cardioverter-defibrillator therapy in
      patients with idiopathic dilated cardiomyopathy.
AB  - Evaluating predictors of appropriate implantable cardioverter-defibrillator (ICD)
      therapy in patients with idiopathic dilated cardiomyopathy (IDC) may be helpful
      in developing risk stratification strategies for these patients. Fifty-four
      patients with IDC underwent ICD implantation and were followed up. Twenty-three
      patients (42%) had a class I indication for ICD implantation; the remaining
      patients underwent implantation for multiple risk factors for sudden death
      including left ventricular dysfunction, nonsustained ventricular tachycardia,
      syncope, or positive electrophysiologic study results. Clinical,
      electrocardiographic, and electrophysiologic data were collected. Appropriate ICD
      therapy was defined as an antitachycardia pacing therapy or shock for
      tachyarrhythmia determined to be either ventricular tachycardia or ventricular
      fibrillation. Appropriate ICD therapy was observed in 23 patients (42%). There
      was a significant difference in use of beta-blocker therapy between patients who
      did and did not have appropriate ICD therapy (p <0.0003). Cox regression analysis
      identified the following univariate predictors (p <0.1): class I indication (p
      <0.005) and lack of use of beta-blocker therapy (p <0.0007). In multivariate
      analysis, only lack of beta-blocker use (relative risk 0.15, 95% confidence
      intervals 0.05 to 0.45; p <0.0007) was identified as a predictor of appropriate
      ICD therapy. Of the patients who received ICD therapy, only 4 (17%) were taking
      beta blockers, whereas 21 of the 31 patients (68%) who did not receive ICD
      therapy were treated with beta blockers (p <0.0003). In patients with IDC
      selected for ICD implantation, the most consistent predictor of appropriate ICD
      therapy was lack of beta-blocker use. Attempts should be made to administer beta
      blockers to these patients, if tolerated.

PMID- 11988199
TI  - Usefulness of magnetic resonance imaging dobutamine stress in asymptomatic and
      minimally symptomatic patients with decreased cardiac reserve from congenital
      heart disease (complete and corrected transposition of the great arteries and
      subpulmonic obstruction).
AB  - We explored the effect of dobutamine stress and its possible clinical
      implications in different groups of asymptomatic patients with chronic right
      ventricular (RV) pressure overload due to congenital heart disease. Forty-seven
      asymptomatic and minimally symptomatic patients with chronic RV pressure overload
      were studied: 24 patients with systemic right ventricles (16 surgically corrected
      transposition of the great arteries (TGA) (Mustard or Senning), 8 congenitally
      corrected TGA), 23 patients with chronic pressure overloaded subpulmonic right
      ventricles, and 11 age- and sex-matched healthy volunteers. Magnetic resonance
      imaging (MRI) was performed both at baseline and during dobutamine stress to
      determine RV volumes and ejection fraction. At baseline, RV ejection fraction in
      patients with surgically corrected TGA was significantly lower than in controls
      (58 +/- 10% vs 70 +/- 8%, p = 0.02). During dobutamine stress, RV ejection
      fraction increased significantly in controls and patient groups except for
      patients with pressure overloaded subpulmonic right ventricles. RV stroke volume
      increased in controls (21 +/- 21%, p = 0.008); RV stroke volume remained
      unchanged in patients with congenitally corrected TGA and surgically corrected
      TGA (2 +/- 17%, p = NS; -8 +/- 29%, p = NS). A significant RV stroke volume
      decrease was observed in patients with subpulmonic right ventricles (-15 +/- 16%,
      p = 0.0002). The changes in RV stroke volume were accompanied by a significant
      decrease in RV end-diastolic volume (-13 +/- 14%, p = 0.001) in patients with
      subpulmonic right ventricles and in patients with surgically corrected TGA (-23
      +/- 16%, p = 0.0001). In controls and in patients with congenitally corrected TGA
      there was no change in RV end-diastolic volume (3 +/- 15%, p = NS; -5 +/- 11%, p
      = NS). There is a clear heterogeneity in response to MRI dobutamine stress
      between different groups of patients with chronic RV pressure overload. Our data
      suggest impaired filling in surgically corrected TGA and decreased contractility
      in patients with chronic pressure overloaded subpulmonic right ventricles.
      Dobutamine stress MRI may facilitate follow-up of RV (dys)function in patients
      with chronic RV pressure overload due to congenital heart disease.

PMID- 11988200
TI  - Transcatheter patch correction of secundum atrial septal defects.
AB  - The efficacy and safety of the transcatheter patch (TP) correction of a secundum
      atrial septal defect (ASD) was studied acutely and on short-term follow-up in 20
      patients, successfully implanted with the device. TPs are made of polyurethane
      foam and require temporary balloon catheter immobilization on the atrial septum
      for 48 hours. Eighteen patients were not suitable for disk-device repair. The
      patient median age and ASD diameter were 37 years and 26 mm, respectively.
      Eighteen patients had immediate effective ASD occlusion; 2 patients had
      significant residual shunts. Premature leaks of the supportive balloons were
      responsible for the residual shunts. One of the patients with residual shunt
      received a second patch 6 months later with full occlusion. All patients with
      implants were doing well up to 24 months after implantation. Existing symptoms
      improved although residual shunts remained; septal anatomy was normalized, with
      the patched area becoming progressively indistinguishable from the rest of the
      septum. In conclusion, TP occlusion of secundum ASD is feasible and effective
      even for defects unsuitable for disk-device repair. The method appears safe
      acutely and on short-term follow-up, with symptomatic improvement and
      normalization of septal anatomy.

PMID- 11988201
TI  - William Watts Parmley, MD: a conversation with the editor.

PMID- 11988202
TI  - Postoperative ventricular function and cardiac enzymes after on-pump versus off
      pump CABG surgery.

PMID- 11988203
TI  - Intravascular ultrasound findings in patients with acute coronary syndromes with
      and without elevated troponin I level.

PMID- 11988204
TI  - Usefulness of implantable cardioverter-defibrillators in refractory variant
      angina pectoris complicated by ventricular fibrillation in patients with
      angiographically normal coronary arteries.

PMID- 11988205
TI  - Relation between markers of systemic vascular inflammation and smoking in women.

PMID- 11988206
TI  - Long-term outcomes on quality-of-life and health care costs in patients with
      supraventricular tachycardia (radiofrequency catheter ablation versus medical
      therapy).

PMID- 11988207
TI  - Long-term follow-up of fast pathway radiofrequency ablation in atrioventricular
      nodal reentrant tachycardia.

PMID- 11988208
TI  - Effect of amiodarone +/- diltiazem +/- beta blocker on frequency of atrial
      fibrillation, length of hospitalization, and hospital costs after coronary artery
      bypass grafting.

PMID- 11988209
TI  - Transthoracic Doppler echocardiographic measurement of flow velocity and flow
      velocity reserve in the great cardiac vein and in the left anterior descending
      coronary artery in children with left ventricular volume overload secondary to
      ventricular septal defect.

PMID- 11988210
TI  - Effect of cocaine usage on C-reactive protein, von Willebrand factor, and
      fibrinogen.

PMID- 11988211
TI  - Frequency of coronary ostial aneurysms after aortic root surgery in patients with
      the Marfan syndrome.

PMID- 11988212
TI  - Relation of baseline forearm vasodilator reserve to vascular endothelial response
      to estrogen replacement therapy in healthy postmenopausal women.

PMID- 11988213
TI  - Coronary flow reserve and brachial artery reactivity in patients with chest pain
      and "false positive" exercise-induced ST-segment depression.

PMID- 11988215
TI  - Rat abdominal aortic stenting: a simple model displaying in-stent restenosis.

PMID- 11988216
TI  - Is dealcoholized red wine the final solution? The Japanese paradox.

PMID- 11988217
TI  - A voltage-independent K+ conductance activated by cell swelling in Ehrlich cells
      is modulated by a G-protein-mediated process.
AB  - Cell swelling following hypoosmotic stress leads to the activation of volume
      sensitive ion channels that allow a K+ and Cl- efflux accompanied by water loss.
      A Ca2+-insensitive K+ channel (I(K,vol)) has been described in Ehrlich cells that
      can be activated by hypotonicity and leukotriene D4 and is inhibited by
      clofilium. We have studied the activation and deactivation by osmotic stimuli of
      this channel. A G-protein appears to be involved in these processes since GTP
      gamma-S accelerates deactivation, while GDP-beta-S blocks the channel in the open
      state, a result mimicked by pertussis toxin (PTX). In addition, PTX accelerates
      the onset of I(K,vol). We propose that I(K,vol) is tonically inhibited by a PTX
      sensitive G-protein.

PMID- 11988218
TI  - Protein-translocating outer membrane porins of Gram-negative bacteria.
AB  - Five families of outer membrane porins that function in protein secretion in Gram
      negative bacteria are currently recognized. In this report, these five porin
      families are analyzed from structural and phylogenetic standpoints. They are the
      fimbrial usher protein (FUP), outer membrane factor (OMF), autotransporter (AT),
      two-partner secretion (TPS) and outer membrane secretin (Secretin) families. All
      members of these families in the current databases were identified, and all full
      length homologues were multiply aligned for structural and phylogenetic analyses.
      The organismal distribution of homologues in each family proved to be unique with
      some families being restricted to proteobacteria and others being widespread in
      other bacterial kingdoms as well as eukaryotes. The compositions of and size
      differences between subfamilies provide evidence for specific orthologous
      relationships, which agree with available functional information and intra
      subfamily phylogeny. The results reveal that horizontal transfer of genes
      encoding these proteins between phylogenetically distant organisms has been
      exceptionally rare although transfer within select bacterial kingdoms may have
      occurred. The resultant in silico analyses are correlated with available
      experimental evidence to formulate models relevant to the structures and
      evolutionary origins of these proteins.

PMID- 11988219
TI  - Specific interactions of the antimicrobial peptide cyclic beta-sheet tachyplesin
      I with lipopolysaccharides.
AB  - The cyclic beta-sheet antimicrobial peptide tachyplesin I (T-SS) was found to
      show 280-fold higher affinity for lipopolysaccharides (LPS) compared with acidic
      phospholipids, whereas the linear alpha-helical peptide F5W-magainin 2 (MG2)
      could not discriminate between LPS and acidic phospholipids. The recognition site
      was the lipid A moiety and the cyclic structure was crucial to this specific
      binding. The cyclic structure also endowed the peptide with very rapid outer
      membrane (OM) permeabilization.

PMID- 11988220
TI  - Magainin 2 in phospholipid bilayers: peptide orientation and lipid chain ordering
      studied by X-ray diffraction.
AB  - We present a structural study of biomimetic lipid bilayers interacting with the
      antimicrobial peptide magainin 2 amide, using grazing incidence X-ray diffraction
      and reciprocal space mapping (RSM) techniques. The short-range order of lipid
      chains in lecithin is found to be strongly reduced by the peptides. From the
      scattering intensity of the chain correlation peak, we can quantify the lateral
      length scale R over which the bilayer structure is affected by peptide binding.
      The non-local perturbation of the bilayer is discussed in the framework of
      bilayer elasticity theory.

PMID- 11988221
TI  - Secondary structure of spiralin in solution, at the air/water interface, and in
      interaction with lipid monolayers.
AB  - The surface of spiroplasmas, helically shaped pathogenic bacteria related to the
      mycoplasmas, is crowded with the membrane-anchored lipoprotein spiralin whose
      structure and function are unknown. In this work, the secondary structure of
      spiralin under the form of detergent-free micelles (average Stokes radius, 87.5
      A) in water and at the air/water interface, alone or in interaction with lipid
      monolayers was analyzed. FT-IR and circular dichroism (CD) spectroscopic data
      indicate that spiralin in solution contains about 25+/-3% of helices and 38+/-2%
      of beta sheets. These measurements are consistent with a consensus predictive
      analysis of the protein sequence suggesting about 28% of helices, 32% of beta
      sheets and 40% of irregular structure. Brewster angle microscopy (BAM) revealed
      that, in water, the micelles slowly disaggregate to form a stable and homogeneous
      layer at the air/water interface, exhibiting a surface pressure up to 10 mN/m.
      Polarization modulation infrared reflection absorption spectroscopy (PMIRRAS)
      spectra of interfacial spiralin display a complex amide I band characteristic of
      a mixture of beta sheets and alpha helices, and an intense amide II band.
      Spectral simulations indicate a flat orientation for the beta sheets and a
      vertical orientation for the alpha helices with respect to the interface. The
      combination of tensiometric and PMIRRAS measurements show that, when spiroplasma
      lipids are used to form a monolayer at the air/water interface, spiralin is
      adsorbed under this monolayer and its antiparallel beta sheets are mainly
      parallel to the polar-head layer of the lipids without deep perturbation of the
      fatty acid chains organization. Based upon these results, we propose a 'carpet
      model' for spiralin organization at the spiroplasma cell surface. In this model,
      spiralin molecules anchored into the outer leaflet of the lipid bilayer by their
      N-terminal lipid moiety are composed of two colinear domains (instead of a single
      globular domain) situated at the lipid/water interface. Owing to the very high
      amount of spiralin in the membrane, such carpets would cover most if not all the
      lipids present in the outer leaflet of the bilayer.

PMID- 11988222
TI  - Circular dichroic properties and average dimensions of DNA-containing reverse
      micellar aggregates.
AB  - With the aim of investigating the compartmentation of nucleic acids and
      surfactant aggregates, we have studied the circular dichroic properties of DNA
      solubilized in reverse micelles. DNA incorporated in AOT/isooctane reverse
      micelles (AOT=bis-2-ethyl-hexyl sodium sulfosuccinate) assumes an anomalous
      circular dichroism (CD) spectrum with the characteristic features of a psi
      spectrum. Older literature observations could therefore be confirmed that
      attribute these spectral changes to the fact that the reverse micelles induce the
      formation of a condensed form of DNA. A dynamic light scattering (DLS)
      characterization of the DNA-containing micellar solutions was carried out, and
      three populations of aggregates in a polar solvent are observed, with an average
      radius centered at 5, 100 and 1000 nm, respectively, all three containing DNA.
      Several forms of DNA, including a plasmid, have been investigated. The formation
      of 1 microm-large aggregates depends on the DNA concentration and such aggregates
      disappear in the course of a few hours. Conversely, the 100 nm aggregates are
      stable for at least 1 day and contain DNA in a normal spectral state at low
      concentration and in a condensed form-it is the characteristic psi spectrum-in a
      higher concentration range. The solubilization of DNA in reverse micelles brings
      about unexpected larger structures in hydrocarbon solution, and whereas the very
      large component can be with all likelihood be attributed to clusters of smaller
      reverse micelles, the components at 100 nm radius appear to be a quite stable and
      characteristic feature of DNA-containing reverse micelles.

PMID- 11988223
TI  - Pore formation activity of Cry1Ab toxin from Bacillus thuringiensis in an
      improved membrane vesicle preparation from Manduca sexta midgut cell microvilli.
AB  - The pore formation activity of Cry1Ab toxin is analyzed in an improved membrane
      preparation from apical microvilli structures of Manduca sexta midgut epithelium
      cells (MEC). A novel methodology is described to isolate MEC and brush border
      membrane vesicles (BBMV) from purified microvilli structures. The specific
      enrichment of apical membrane enzyme markers aminopeptidase (APN) and alkaline
      phosphatase (APh) were 35- and 22-fold, respectively, as compared to the whole
      midgut cell homogenate. Ligand-blot and Western-blot experiments showed that
      Cry1A specific receptors were also enriched. The pore formation activity of
      Cry1Ab toxin was fourfold higher in the microvilli membrane fraction that showed
      low intrinsic K+ channels and higher APN and APh activities than in the basal
      lateral membrane fraction harboring high intrinsic K+ channels. These data
      suggest that basal-lateral membrane was separated from apical membrane.This
      procedure should allow more precise studies of the interaction of Cry toxins with
      their target membranes, avoiding unspecific interaction with other cellular
      membranes, as well as the study of the pore formation activity induced by Cry
      toxins in the absence of endogenous channels from M. sexta midgut cells.

PMID- 11988224
TI  - Somatostatin (SRIF) and SRIF receptors in the mouse retina.
AB  - In the retina, somatostatin (SRIF) acts as a neuromodulator by interacting with
      specific SRIF subtype (sst) receptors. The aim of this study was to detect mRNAs
      for sst(1-5) receptors by semiquantitative RT-PCR and to determine the cellular
      localization of either SRIF or individual SRIF receptor immunoreactivities. Size,
      density and absolute number of immunolabeled somata were measured using computer
      assisted image analysis. With RT-PCR we found that all five sst receptor mRNAs
      were expressed, with highest levels of sst(2) and sst(4) receptors. SRIF
      immunolabeling was localized to sparse-occurring amacrine cells in the inner
      nuclear layer (INL) and to displaced amacrine cells in the ganglion cell layer
      (GCL). sst(2A) receptors were localized to protein kinase- (PKC) immunoreactive
      (IR) rod bipolar cells, calbindin- (CaBP-) IR horizontal cells, tyrosine
      hydroxylase- (TH-) IR amacrine cells and glycinergic amacrine cells. None of the
      sst(2A)-IR amacrine cells were found to express parvalbumin (PV)
      immunoreactivity. sst(4) receptor immunolabeling was localized to CaBP-IR and
      CaBP-non-IR cells in the GCL that originated long process bundles in the GC axon
      layer. These cells were not observed after optic nerve transection and they were
      therefore interpreted as ganglion cells. Quantitative analysis showed that all of
      the PKC-IR rod bipolar cells, CaBP-IR horizontal cells, and TH-IR amacrine cells
      and 5% of the glycinergic amacrine cells expressed sst(2A) receptors. In
      addition, 4-6% of the putative ganglion cells expressed sst(4) receptors. The
      localization of SRIF to sparse-occurring retinal neurons, together with the
      widespread expression of sst(2A) and sst(4) receptors suggests that SRIF acts at
      multiple levels of retinal circuitry. These results provide a database for
      investigations of the functional retinal networks in mice with genetic
      alterations of somatostatinergic transmission.

PMID- 11988225
TI  - 17 beta-estradiol treatment retards excitotoxic delayed degeneration in
      substantia nigra reticulata neurons.
AB  - Estrogen treatment offers neuro-protection in animal experiments in which
      excitotoxic mechanisms destroy neurons. In a model of delayed neuronal
      degeneration that depends on excitotoxicity, we tested whether females had an
      altered susceptibility, and whether physiologic doses of estrogen administered
      after the brain insult would protect susceptible neurons. Females were
      ovariectomized, exposed to striatal-pallidal ibotenic acid injury that caused
      delayed degeneration of substantia nigra neurons, and treated with 17 beta 
      estradiol (30 microg, subcutaneously every other day, beginning 2 days after the
      striatal injury) or vehicle. At 6 and 8 days post lesion, the 17beta-estradiol
      treatment group maintained over 87 and 70% of control nigral neuron number,
      respectively. Physiologic levels of estrogen delivered days after the excitotoxic
      stress completely protected neurons in the substantia nigra reticulata 6 days
      post lesion and slowed degeneration 8 days post lesion.

PMID- 11988226
TI  - Regulation of the glutamate uptake by extracellular calcium.
AB  - To determine whether [Ca(2+)](e) modulates glutamate re-uptake, we studied the
      uptake mechanism into rat cerebrocortical synaptosomes. The removal of
      extracellular Ca(2+) caused a negative modulation in the uptake mechanism. The
      calculated K(50) value was 0.185 +/- 0.019 mM (n = 4). The Michaelis-Menten data
      analysis indicate that absence of Ca(2+) diminished the V(max) kinetic parameter
      by about 60% without changing significantly the K(m) suggesting a non-competitive
      mechanism. We also tested the involvement of intracellular Ca(2+) in this
      phenomenon by trapping BAPTA into the synaptosomal vesicles to control the Ca(2+)
      concentration. Our results suggest that intracellular Ca(2+) changes have a less
      predominant role on the glutamate uptake than do extracellular Ca(2+). These
      findings argue in favor of an important role of extracellular [Ca(2+)] in
      maintaining the L-glutamate re-uptake mechanism in the mammalian central nervous
      system.

PMID- 11988227
TI  - Repeated interactions with females elevate metabolic capacity in the limbic
      system of male rats.
AB  - The effect of heterosexual social experience on brain metabolic capacity was
      investigated by measuring the activity of cytochrome oxidase, a rate-limiting
      enzyme in oxidative metabolism. Male Sprague-Dawley rats were kept naive or
      allowed to copulate with receptive females three (3 F males) or 16 times (16 F
      males). Throughout the vomeronasal system and other limbic areas, 16 F males had
      elevated metabolic capacity relative to naive and 3 F males, whereas no
      significant differences in brain metabolism were found between 3 F and naive
      males. Behavioral differences were also found between 3 F and 16 F males. In a
      second experiment, we assessed differences in brain metabolism between sexually
      active and inactive males given only one opportunity to copulate and found no
      significant difference in neural metabolism between these males. This suggests
      that the differences found in the first experiment were primarily driven by
      differences in repeated experience rather than by sexual performance between 16 F
      and 3 F males. We speculate that these changes in brain metabolic capacity could
      be related to immediate early gene expression during copulation and could
      underlie the long-term behavioral changes accompanying heterosexual social
      experience.

PMID- 11988228
TI  - Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild
      type and tau mutant Syrian hamsters.
AB  - Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in
      studies of circadian rhythms, there are no data available on the temporal
      dynamics of the neuropeptide vasopressin (AVP), a major output system of the
      suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in vivo
      across the light period and in vitro using long-term organotypic SCN cultures.
      Additionally, we compared wild-type and tau mutant hamsters with an endogenous
      circadian period of approximately 24 h and approximately 20 h, respectively. The
      in vivo study revealed no differences in the number of SCN-AVP neurons between
      the two genotypes of hamsters studied at three time points across the light
      period of the circadian cycle. A significantly higher level of AVP
      immunoreactivity, however, was found in the SCN of wild-type compared to tau
      mutant hamsters at the beginning and in the middle of the light period, but not
      at the end of the light period. SCN-AVP cell number and immunostaining decreased
      significantly across the light period in wild-type hamsters, but not in tau
      mutants. The in vitro study revealed a significantly higher rate of AVP release
      per 24 h from the tau mutant SCN compared to the wild-type SCN. Robust circadian
      oscillations in AVP release were not found in either type of hamster. These
      results may suggest that the SCN-AVP system of hamsters, irrespective of
      genotype, is relatively weak compared to other species. Moreover, the tau
      mutation seems to influence the SCN-AVP system by enhancing the rate of AVP
      release and by reducing AVP content and its daily fluctuation.

PMID- 11988229
TI  - Source activity in the human secondary somatosensory cortex depends on the size
      of corpus callosum.
AB  - If corpus callosum (CC) mediates the activation of the secondary somatosensory
      area (SII) ipsilateral to the side of stimulation, then the peak latencies of the
      contra- and ipsilateral SII activity as well as the amplitude of the ipsilateral
      SII activity should correlate with the size of CC. Innocuous electrical stimuli
      of five different intensities were applied to the ventral surface of the right
      index finger in 15 right-handed men. EEG was recorded using 82 closely spaced
      electrodes. The size of CC and of seven callosal regions was measured from the
      mid-sagittal slice of a high-resolution anatomical MRI. The activation in the
      contralateral and ipsilateral SII was evaluated using spatio-temporal source
      analysis. At the strongest stimulus intensity, the size of the intermediate part
      of the callosal truncus correlated negatively with the interpeak latency of the
      sources in ipsi- and contralateral SII (r = -0.83, P < 0.01). Stepwise regression
      analysis showed that the large size of the intermediate truncus of CC was
      paralleled by a latency reduction of peak activity of the ipsilateral SII,
      whereas both contra- and ipsilateral peak latencies were positively correlated.
      The peak amplitude of the ipsilateral SII source correlated positively with the
      size of the intermediate truncus of CC, and with the peak amplitudes of sources
      in the primary somatosensory cortex (SI) and in the mesial frontal cortex. The
      results suggest that in right-handed neurologically normal men, the size of the
      intermediate callosal truncus contributes to the timing and amplitude of
      ipsilateral SII source activity.

PMID- 11988230
TI  - Effects of catecholamine uptake blockers in the caudate-putamen and subregions of
      the medial prefrontal cortex of the rat.
AB  - Altered dopamine regulation in the medial prefrontal cortex has been linked to
      drug abuse and disorders such as schizophrenia. Heterogeneous expression of the
      dopamine transporter, as well as the ability of the norepinephrine transporter to
      clear dopamine in the prefrontal cortex, delineates two potential sites for the
      regulation of synaptic dopamine within the cortex. The present study used in vivo
      microdialysis to compare the effects of local infusions of dopamine and
      norepinephrine uptake blockers in the caudate putamen and two subregions of the
      prefrontal cortex, the anterior cingulate and prelimbic/infralimbic cortices.
      Results revealed that all dopamine uptake blockers produced greater increases in
      dopamine efflux in the caudate-putamen relative to the prefrontal cortex. In
      addition, amphetamine administration increased dopamine efflux to a greater
      degree in the prelimbic, relative to the anterior cingulate, cortex. In contrast,
      the increase in dopamine efflux was similar in both subregions in the presence of
      nomifensine and desmethylimipramine. Infusions of the selective dopamine uptake
      blocker GBR 12909 failed to alter dopamine efflux in any prefrontocortical
      subregion. These data indicate a more prominent role for the dopamine transporter
      in the clearance of extracellular dopamine in the caudate-putamen relative to the
      prefrontal cortex and an important role for NET in the clearance of dopamine in
      both the prelimbic and anterior cingulate subregions of the rat medial prefrontal
      cortex.

PMID- 11988231
TI  - A chronic treatment with fluoxetine decreases 5-HT(1A) receptors labeling in mice
      selected as a genetic model of helplessness.
AB  - Two lines of mice were bred for their opposite helpless behavior in the tail
      suspension test, i.e., helpless (HL) mice and non helpless (NHL) mice. The 5
      HT(1A) receptor labeling was quantified by means of autoradiography with (3)H-8
      OH-DPAT on brain sections from mice of these two lines. We observed a
      significantly higher level of (3)H-8-OH-DPAT binding sites density in HL mice
      comparatively to NHL mice, in the medial prefrontal, cingulate, motor and
      sensorial cortices, in several regions of the limbic system, such as CA3 field of
      hippocampus, dentate gyrus, medial and baso-medial amygdala, and in dorsal and
      median raphe nuclei. A chronic 21-day treatment with the antidepressant
      fluoxetine (10 mg/kg, i.p. daily) attenuated significantly the spontaneous
      helplessness in HL mice but did not alter the behavior of NHL mice. In the brain
      of HL mice chronically injected with fluoxetine, the elevated (3)H-8-OH-DPAT
      binding sites density was no longer observed after treatment in several regions,
      among which the raphe nuclei. Conversely, the antidepressant treatment did not
      modify the (3)H-8-OH-DPAT binding sites density in NHL mice. The variation of 5
      HT(1A) receptors binding density in the HL mice in response to a chronic
      fluoxetine treatment parallels the attenuation of the spontaneous helplessness
      observed in the tail suspension test, and may underlie this behavior.

PMID- 11988232
TI  - Age-related changes in cerebral blood flow and glucose metabolism in conscious
      rhesus monkeys.
AB  - Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of
      glucose (rCMRglc) were measured in aged and young monkeys by positron emission
      tomography (PET). Our purpose was to examine whether the age-related changes
      observed in the human brain also occur in the monkey brain. Studies were
      performed on six aged and six young-adult male rhesus monkeys (Macaca mulatta).
      rCBF and the rCMRglc were serially measured using PET with [(15)O]H(2)O and 2
      [(18)F]fluoro-2-deoxy-D-glucose (FDG), respectively. In order to minimize the
      bias induced by anesthesia, the PET emission scans were performed in the
      conscious state. ROIs were taken for the cerebellum, hippocampus with adjacent
      cortex, striatum, occipital cortex, temporal cortex, frontal cortex and
      cingulate. Group differences and correlations between rCBF and rCMRglc in each
      group were determined. Aged monkeys had significantly lower rCBF in the
      cerebellum, hippocampus with the adjacent cortex, striatum, occipital cortex,
      temporal cortex, frontal cortex, and significantly lower rCMRglc in the
      cerebellum, hippocampus with the adjacent cortex, striatum, occipital cortex,
      temporal cortex, frontal cortex and cingulate, compared to young monkeys. There
      were significant correlations between rCBF and rCMRglc in both the aged and young
      groups, but no significant difference was found in relationship between the two
      groups. Age-related changes were observed not only in rCMRglc, but also in rCBF
      in aged monkeys, while the coupling between rCBF and rCMRglc was maintained even
      in aged monkeys. These results demonstrated the potential of aged monkeys to
      serve as an aged human model using PET.

PMID- 11988233
TI  - Mouse strain variation in maximal electroshock seizure threshold.
AB  - Maximal electroshock seizure threshold (MEST) is a classical measure of seizure
      sensitivity with a wide range of experimental applications. We determined MEST in
      nine inbred mouse strains and one congenic strain using a procedure in which mice
      are given one shock per day with an incremental (1 mA) current increase in each
      successive trial until a maximal seizure (tonic hindlimb extension) is elicited.
      C57BL/6J and DBA/2J mice exhibited the highest and lowest MEST, respectively,
      with the values of other strains falling between these two extremes. The relative
      rank order of MEST values by inbred strain (highest to lowest) is as follows:
      C57BL/6J > CBA/J = C3H/HeJ > A/J > Balb/cJ = 129/SvIMJ = 129/SvJ > AKR/J >
      DBA/2J. Results of experiments involving a single electroconvulsive shock given
      to separate groups of mice at different current intensities suggest that
      determination of MEST by the method used is not affected by repeated sub-maximal
      seizures. Overall, results document a distinctive mouse strain distribution
      pattern for MEST. Additionally, low within strain variability suggests that
      environmental factors which affect quantification of MEST are readily controlled
      under the conditions of this study. We conclude that MEST represents a useful
      tool for dissecting the multifactorial nature of seizure sensitivity in mice.

PMID- 11988234
TI  - Characterization of diet-induced obese rats that develop persistent obesity after
      6 months of high-fat followed by 1 month of low-fat diet.
AB  - A subset of Sprague-Dawley rats developed persistent obesity when maintained on a
      high-fat diet for 6 months followed by a low-fat diet for 1 month, while another
      subset from the same cohort of rats remained lean on the same diet regimens. The
      diet-induced obese (DIO) rats had higher energy intake than expenditure, while
      diet-resistant (DR) rats maintained energy balance. DIO rats also had an
      increased respiratory quotient and higher levels of plasma leptin, insulin and
      cholesterol. In the hypothalamic areas, DIO rats had elevated NPY and AGRP mRNA,
      but not MCH mRNA. Our data suggest that the increase in hypothalamic expression
      of NPY and AGRP may contribute to the development of persistent obesity in DIO
      rats.

PMID- 11988235
TI  - Relationship between zinc and neurotransmitters released into the amygdalar
      extracellular space.
AB  - On the basis of the evidence that vesicular zinc may be essential to the
      functions of the amygdala, the movement and action of actively functioning zinc
      in synapses in the amygdala of rats were studied using in vivo microdialysis. The
      increase of (65)Zn release into the amygdalar extracellular space during
      stimulation with high K(+) was inhibited by the addition of 1 microM
      tetrodotoxin. High-K(+)-induced (65)Zn release was not observed in the substantia
      nigra, in which zinc-containing glutamatergic neuron terminals are assumed not to
      exist. The amount of (65)Zn released into the amygdalar extracellular space
      during stimulation with high K(+) was correlated with that of glutamate. These
      results suggest that zinc may be concurrently released with glutamate from the
      neuron terminals in the amygdala and that zinc may cooperate with glutamate in
      excitatory neurotransmission. When the amygdala was perfused with 10 microM
      calcium-ethylenediamine tetraacetic acid (CaEDTA) to chelate zinc in the
      extracellular space, the levels of glutamate in the extracellular space were not
      appreciably influenced, whereas those of gamma-aminobutyric acid (GABA) were
      remarkably increased. It is likely that vesicular zinc modulates GABA release in
      the amygdala. The modulation of GABAergic neuron activity by zinc may be
      important for the functions of the amygdala.

PMID- 11988236
TI  - A lack of dimorphism of sex or sexual orientation in the human anterior
      commissure.
AB  - Four studies have examined the cross-sectional area of the anterior commissure
      (AC) for variation with sex, with conflicting results. One also reported the AC
      to be larger in homosexual as opposed to heterosexual men. We examined the cross
      sectional area of the AC in postmortem material from 120 individuals, and found
      no variation in the size of the AC with age, HIV status, sex, or sexual
      orientation.

PMID- 11988237
TI  - The globalisation of the NHS.

PMID- 11988238
TI  - Clinical trials: when to start and when to stop.

PMID- 11988239
TI  - Multiple sclerosis and type 1 diabetes: an unlikely alliance.

PMID- 11988240
TI  - What options for treatment of hereditary breast cancer?

PMID- 11988241
TI  - Secondary persistent infection with hepatitis C virus: a challenge for adaptive
      immunity.

PMID- 11988242
TI  - Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for
      multiple sclerosis: results of a 2-year prospective randomised multicentre study
      (INCOMIN).
AB  - BACKGROUND: The three interferon beta preparations approved for treatment of
      relapsing-remitting multiple sclerosis (MS) differ in dose and frequency of
      administration. Interferon beta-1a 30 microg is administered once a week,
      interferon beta-1a 22 microg or 44 microg is given three times a week, and
      interferon beta-1b 250 microg is administered on alternate days. No clinical
      study directly comparing the different regimens has been published. The INCOMIN
      study was designed to compare the clinical and magnetic resonance imaging (MRI)
      benefits of on-alternate-day interferon beta-1b 250 microg with once-weekly
      interferon beta-1a 30 microg. METHODS: INCOMIN was a 2-year, prospective,
      randomised, multicentre study. 188 patients with relapsing-remitting MS were
      assigned to interferon beta-1b (n=96) or interferon beta-1a (n=92). Primary
      outcome measures were the proportion of patients free from relapses and that of
      patients free from new proton density/T2 lesions at MRI assessment. Several
      secondary outcome measures were also assessed. Analysis was by intention to
      treat. FINDINGS: Over 2 years, 49 (51%) individuals administered interferon beta
      1b remained relapse-free compared with 33 (36%) given interferon beta-1a relative
      risk of relapse 0.76; 95% CI 0.59-0.9; p=0.03); and 42 (55%) compared with 19
      (26%), respectively, remained free from new T2 lesions at MRI (relative risk of
      new T2 lesion 0.6; 0.45-0.8; p<0.0003). In both groups, the differences between
      the two treatments increased during the second year. There were also significant
      differences in favour of interferon beta-1b in most of the secondary outcome
      measures, including delay of confirmed disease progression. INTERPRETATION: High
      dose interferon beta-1b administered every other day is more effective than
      interferon beta-1a given once a week.

PMID- 11988243
TI  - Patients with multiple sclerosis and risk of type 1 diabetes mellitus in
      Sardinia, Italy: a cohort study.
AB  - BACKGROUND: Individuals from Sardinia, Italy, are at high risk of developing
      multiple sclerosis and type 1 diabetes mellitus. We attempted to assess the
      prevalence in this region of type 1 diabetes mellitus in individuals with
      multiple sclerosis, and to ascertain disease risk factors. METHODS: We did a
      cohort study to assess prevalence of type 1 diabetes in 1090 people with multiple
      sclerosis, and in their parents (n=2180) and siblings (n=3300), all born and
      living in Sardinia. All participants were patients at the multiple sclerosis
      clinic in Cagliari, and were judged representative of the total Sardinian
      outpatients and inpatients. We asked patients whether their parents or siblings
      had multiple sclerosis or diabetes, confirming replies by examining clinical
      records. We identified risk factors for diabetes with univariate and multivariate
      logistic regression analyses. FINDINGS: Diabetes prevalence in people with
      multiple sclerosis was, respectively, about three-fold and five-fold that in
      their healthy siblings (p=0.001) and in the general population (p<0.0001).
      Presence of other relatives with multiple sclerosis conferred increased risk of
      type 1 diabetes to healthy siblings of individuals with multiple sclerosis (odds
      ratio=3.41, p=0.0019). Diabetes risk was six-fold higher in patients with
      relatives having multiple sclerosis than in healthy siblings of multiple
      sclerosis patients without other relatives with the disease (p=0.0001).
      INTERPRETATION: In Sardinian families with genetic inheritance of multiple
      sclerosis type 1 diabetes is prevalent, both in multiple sclerosis patients and
      in healthy siblings. This finding indicates that common genes contribute to
      susceptibility to both diseases in this population.

PMID- 11988244
TI  - Cutaneous mastocytosis.

PMID- 11988245
TI  - Reduced hearing, ownership, and use of hearing aids in elderly people in the UK-
      the MRC Trial of the Assessment and Management of Older People in the Community:
      a cross-sectional survey.
AB  - BACKGROUND: Reduced hearing in elderly people is important because it is
      disabling and potentially treatable. We aimed to assess the prevalence of reduced
      hearing in elderly people and levels of ownership of hearing aids and use.
      METHODS: We have done a cross-sectional survey of people aged at least 75 years
      in 106 family practices in the UK. We obtained self-reported data on hearing
      difficulties for 32,656 people and gave 14,877 a whispered voice test (response
      rate 78%). FINDINGS: 2537 (8%) of 32,656 participants reported a lot of
      difficulty hearing and 13,630 (42%) a little or a lot of difficulty. 3795 (26%)
      of 14877 participants who completed the whispered voice test (95% CI 23-29)
      failed the test, the proportion rising sharply with age. Following wax removal,
      343 passed a retest, leaving 3452 (23%, 20-26) who failed the test, even after
      wax removal if present. 998 (46%) of 2180 people wearing a hearing aid at the
      time of testing failed the whispered voice test. More than half the people who
      failed the test did not own a hearing aid. 2200 (60%) of 3846 people who owned a
      hearing aid said they used it regularly. Level of use was strongly related to
      perceived benefit. INTERPRETATION: Reduced hearing is common and provision of
      hearing aids inadequate in elderly people. Many people who own a hearing aid do
      not use it regularly, and even when wearing their aid many still have socially
      disabling levels of hearing loss. A major source of morbidity in elderly people
      could be alleviated by improvements in detection and management of reduced
      hearing.

PMID- 11988246
TI  - Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status.
AB  - BACKGROUND: Management of early-stage breast cancer in young women with mutations
      in BRCA1 or BRCA2 remains controversial. This study assessed the long-term risks
      of ipsilateral and contralateral breast cancer in a cohort of young women who
      underwent breast-conserving surgery followed by radiotherapy. METHODS: Between
      1975 and 1998, 290 women with breast cancer diagnosed at age 42 years or younger
      underwent lumpectomy followed by radiotherapy at our hospital. We recruited 127
      of these women for complete sequencing of BRCA1 and BRCA2. Demographic, clinical,
      pathological, and outcome data were recorded. The primary endpoints were rates of
      ipsilateral and contralateral breast cancer, in relation to germline BRCA1/2
      status. FINDINGS: 105 women were classified as having sporadic disease (94 with
      wild-type or known polymorphisms and 11 with variants of unclear significance)
      and 22 as having genetic predisposition (deleterious mutations in BRCA1 [15] or
      BRCA2 [seven]). At 12 years of follow-up, the genetic group had significantly
      higher rates of ipsilateral (49% vs 21%, p=0.007) and contralateral events (42%
      vs 9%, p=0.001) than the sporadic group. The majority of events were classified
      as second primary tumours. No patient in the genetic group had undergone
      oophorectomy or was taking prophylactic agents such as tamoxifen. INTERPRETATION:
      Patients with germline mutations in BRCA1 or BRCA2 have a high risk of developing
      late ipsilateral and contralateral second primary tumours. With breast-conserving
      therapy, chemoprophylaxis or other interventions to reduce the rate of second
      cancers may be valuable. Alternatively, bilateral mastectomy may be considered,
      to minimise the risk of second tumours in the breasts.

PMID- 11988247
TI  - Protection against persistence of hepatitis C.
AB  - BACKGROUND: Neither previous hepatitis C virus (HCV) infection nor vaccination
      with HCV-derived antigens protects against reinfection. However, HCV infection
      and vaccination in chimpanzees has been shown to reduce the magnitude and
      duration of viraemia with re-challenge. We aimed to establish whether similar
      immunity could be achieved in man. METHODS: From a study of injecting drug users,
      we identified 164 people who had no evidence of previous HCV infection and 98
      individuals who had been previously, but were not currently, infected with HCV.
      We compared the incidence and persistence of HCV viraemia in these two groups
      over four consecutive 6-month periods. FINDINGS: Of participants without previous
      infection, the incidence of HCV infection was 21% (35/164). By contrast, people
      previously infected were half as likely to develop new viraemia (12% [12/98]),
      even after accounting for risk behaviour (hazard ratio, 0.45; 95% CI 0.23-0.88).
      Furthermore, in HIV-1-negative people, those previously infected were 12 times
      less likely than people infected for the first time to develop persistent
      infection (odds ratio 0.05, 95% CI 0.01-0.30), and median peak HCV RNA
      concentration was two logs lower. HCV persisted in six of six HIV-1-positive
      people, even in one man who had previously cleared HCV infection when he was HIV
      1 negative. INTERPRETATION: There is an alarming frequency of HCV infection and
      persistence among injecting drug users. Our data suggest that immunity against
      viral persistence can be acquired, and that vaccines should be tested to reduce
      the burden of HCV-related liver disease.

PMID- 11988248
TI  - Earl Grey tea intoxication.

PMID- 11988249
TI  - Effect of MRI noise on cochlear function.
AB  - A disadvantage of magnetic resonance imaging (MRI) is the high level of noise
      produced (peaking between 122 dB and 131 dB). We used otoacoustic emissions
      (OAEs) as a method to quantify the effect of MRI-generated noise on the cochlea.
      OAEs were measured in 16 patients before and after MRI and in 16 controls. OAEs
      decreased in patients after MRI, but the controls, who were not exposed to MRI
      noise, showed no decrease over the same period. The change in OAEs shows a clear
      effect of MRI noise on cochlear function, despite use of earplugs. The importance
      of correctly fitted earplugs cannot be underestimated.

PMID- 11988250
TI  - Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants.
AB  - We report three cases of severe hypoxaemia after ibuprofen administration during
      a randomised controlled trial of prophylactic treatment of patent ductus
      arteriosus with ibuprofen in premature infants born at less than 28 weeks of
      gestation. Echocardiography showed severely decreased pulmonary blood flow.
      Hypoxaemia resolved quickly on inhaled nitric oxide therapy. We suggest that
      investigators involved in similar trials pay close attention to pulmonary
      pressure if hypoxaemia occurs after prophylactic administration of ibuprofen.

PMID- 11988251
TI  - Vertical transmission of hepatitis B virus despite maternal lamivudine therapy.
AB  - Lamivudine given during the last weeks of pregnancy in women with chronic
      hepatitis B has been reported to be safe. We report a case of chronic hepatitis B
      virus (HBV) infection in a newborn, despite suppression of HBV DNA to
      undetectable levels in the mother by prolonged lamivudine therapy. The newborn
      had raised alanine aminotransferase concentrations and was positive for HBV DNA
      at birth which persisted until 9 months of age, despite neonatal vaccination,
      treatment with hepatitis B immune globulin, and high concentrations of anti-HBs.
      On HBV DNA sequencing, complete sequence homology and a similar precore mutation
      was found in the mother and child, indicating vertical transmission. Lamivudine
      therapy might not prevent perinatal transmission of HBV infection in every
      newborn.

PMID- 11988252
TI  - Limited efficacy of alcohol-based hand gels.
AB  - Alcohol-based gels have been introduced recently in many hospitals worldwide for
      hand antisepsis. We investigated the antimicrobial efficacy of ten gels and four
      rinses according to European standards (EN 1500). No gel met the EN 1500
      requirements within 30 s of application, whereas all hand rinses did. The tested
      hand gels should be considered a retrograde step for hand hygiene because the
      application time in clinical practice is often shorter than 30 s; they should not
      replace alcohol-based liquid hand disinfectants currently used in hospitals or be
      implemented as first choice agents.

PMID- 11988253
TI  - FDA recommends bringing controversial IBS drug back.

PMID- 11988255
TI  - Expert panel unsure of HRT benefits for conditions other than menopause.

PMID- 11988256
TI  - Uganda leads the way on Africa Malaria Day.

PMID- 11988257
TI  - High-risk medical care in war-torn Nepal.

PMID- 11988258
TI  - UK's budget commits to rebuild National Health Service.

PMID- 11988259
TI  - Germany's generic-drug law prompts concern among doctors.

PMID- 11988260
TI  - S Africa shifts AIDS drug stance for rape victims.

PMID- 11988262
TI  - Development of vaccines against meningococcal disease.
AB  - Neisseria meningitidis is a major cause of bacterial meningitis and sepsis.
      Polysaccharide-protein conjugate vaccines for prevention of group C disease have
      been licensed in Europe. Such vaccines for prevention of disease caused by groups
      A (which is associated with the greatest disease burden worldwide), Y, and W135
      are being developed. However, conventional approaches to develop a vaccine for
      group B strains, which are responsible for most cases in Europe and the USA, have
      been largely unsuccessful. Capsular polysaccharide-based vaccines can elicit
      autoantibodies to host polysialic acid, whereas the ability of most non-capsular
      antigens to elicit broad-based immunity is limited by their antigenic diversity.
      Many new membrane proteins have been discovered during analyses of genomic
      sequencing data. These antigens are highly conserved and, in mice, elicit serum
      bactericidal antibodies, which are the serological hallmark of protective
      immunity in man. Therefore, there are many promising new vaccine candidates, and
      improved prospects for development of a broadly protective vaccine for group B
      disease, and for control of all meningococcal disease.

PMID- 11988263
TI  - Dilemmas and opportunities for an appropriate health-service response to violence
      against women.
AB  - This article is an overview of the role of health services in secondary and
      tertiary prevention of intimate partner violence. In it, I review the evidence,
      which comes mostly from developed countries, on the effectiveness and limitations
      of in-service training programmes to identify and care for women who have
      experienced intimate partner violence. I also discuss recent initiatives in
      developing countries to integrate concerns on gender-based violence into health
      care services at different levels, some of the dilemmas and challenges posed by
      the current approaches to intimate partner violence, and recommendations for
      future interventions.

PMID- 11988264
TI  - Uses of error.

PMID- 11988266
TI  - Psychological trauma of the civil war in Sri Lanka.

PMID- 11988265
TI  - Myocardial infarction: is evidence-based medicine the best?

PMID- 11988269
TI  - Physicians persecuted for ethical practice in Nepal.

PMID- 11988270
TI  - Sexual behaviour at the millenium.

PMID- 11988271
TI  - Sexual behaviour at the millenium.

PMID- 11988272
TI  - Sexual behaviour at the millennium.

PMID- 11988273
TI  - BCG efficacy and tuberculin skin testing.

PMID- 11988274
TI  - Sexual behaviour at the millennium.

PMID- 11988275
TI  - Sexual behaviour at the millennium.

PMID- 11988276
TI  - Polyclonal intravenous immunoglobulin to prevent brain injury in preterm infants.

PMID- 11988277
TI  - Polyclonal intravenous immunoglobulin to prevent brain injury in preterm infants.

PMID- 11988279
TI  - A teenager with rash and fever.

PMID- 11988280
TI  - Priority-setting decisions for new cancer drugs.

PMID- 11988282
TI  - Priority-setting decisions for new cancer drugs.

PMID- 11988283
TI  - HIV-1 shedding in genital tract of infected women.

PMID- 11988284
TI  - HIV-1 shedding in genital tract of infected women.

PMID- 11988285
TI  - HIV-1 shedding in genital tract of infected women.

PMID- 11988286
TI  - The African challenge.

PMID- 11988287
TI  - The African challenge.

PMID- 11988288
TI  - The African challenge.

PMID- 11988290
TI  - Mathematical significance.

PMID- 11988291
TI  - Private health in India.

PMID- 11988292
TI  - Medical waste.

PMID- 11988294
TI  - From the medical museum. Lettsom's morning walk.

PMID- 11988303
TI  - Future perfect?

PMID- 11988304
TI  - From follicle culture to nuclear transfer and embryonic stem cells. Proceedings
      of the XIIth International Workshop on Development and Function of the
      Reproductive Organs. Ma'ale HaHamisha, Israel. April 30-May 4, 2001.

PMID- 11988305
TI  - Functional analysis of oocyte-expressed genes using transgenic models.
AB  - An oocyte's journey is highly distinct from the vast majority of cells in the
      body. As one of the largest and rarest cells, oocytes express unique genes
      required for the genesis of healthy and competent eggs. The function of only a
      handful of oocyte-specific genes is beginning to be unraveled. Transgenic mouse
      models have proven to be extremely valuable in studying the effects of gene
      deletions on oocytes and surrounding somatic cells. Growth differentiation factor
      9 (Gdf9), bone morphogenetic protein 15 (Bmp15), zona pellucida genes (Zp1, Zp2
      and Zp3), factor in the germline alpha (Figla), and the c-mos protooncogene (c
      mos) are some of the genes preferentially expressed in oocytes which play
      important roles during folliculogenesis. In order to identify other novel genes
      preferentially expressed in oocytes, we have utilized subtractive hybridization
      and in silico subtraction. The combination of these identification approaches,
      coupled with the use of knockout mice, will lead to many future functional
      studies of genes uniquely devoted to oogenesis and folliculogenesis.

PMID- 11988306
TI  - The initiation of follicle growth: the oocyte or the somatic cells?
AB  - The initiation of follicle growth is defined as the transition of primordial
      follicles from the quiescent to the growth phase. We have shown that follicle
      growth initiation consists of two distinct, consecutive phases. The first phase
      is characterized by the transformation of granulosa cells from flattened to
      cuboidal in shape and by their proliferation, this coincides with follistatin
      expression. During the second phase, an increase in the number of granulosa cells
      is accompanied by an increase in the size of the oocyte. Evidence from other
      species confirms this observation. It seems that a prerequisite for initiation of
      oocyte growth is the presence of cuboidal granulosa cells. The vast majority of
      bovine primordial follicles enter the first phase of growth when cultured in
      serum-free medium. Similar results have been obtained for human primordial
      follicles. Two proteins of oocyte origin, GDF9 and BMP15, play an essential role
      in granulosa cell proliferation beyond the primary stage. It can be speculated
      that the regulation of follicle growth initiation is a two-phase event: the first
      phase depends on locally produced inhibitory and stimulatory factor(s); in the
      second phase the follicle become an autonomous unit, whose further development
      depends on oocyte-produced GDF9/BMP15 and the kit ligand derived from granulosa
      cells.

PMID- 11988307
TI  - Non-invasive analysis of rat ovarian angiogenesis by MRI.
AB  - Magnetic resonance imaging (MRI) was employed for non-invasive analysis of
      vascular remodeling during follicular maturation in the PMSG/hCG rat ovary model.
      Changes in water diffusion and in perfusion led us to suggest that hypoxic stress
      may be a component in the regulation of angiogenesis in the growing follicle.
      However, in contrast with solid tumors of similar size, the spatial and temporal
      pattern of expression of vascular endothelial growth factor (VEGF), did not match
      the angiogenic response. The mismatch could be explained by the role of
      hyaluronan as a high molecular weight suppressor of angiogenesis maintaining an
      avascular follicular antrum.

PMID- 11988308
TI  - Connective tissue growth factor in the ovarian paracrine system.
AB  - The endocrine actions of follicle stimulating hormone and luteinising hormone on
      ovarian cells are transduced by locally produced paracrine factors that regulate
      the formation of extracellular matrix, proteolytic enzymes and protease
      inhibitors, which continuously remodel the parenchymal environment in which
      follicles develop. We recently identified connective tissue growth factor (CTGF)
      as a gene expressed during the predifferentiated stage of granulosa cell
      development in rat ovary. The CTGF gene encodes a protein that is implicated in
      the regulation of connective tissue synthesis, mototaxis, angiogenesis and
      cellular interaction with ECM at various sites in the body. Stimulation of
      granulosa cells by FSH in vitro and in vivo induces follicular maturation
      associated with down-regulation of granulosa cell CTGF mRNA expression. The gene
      remains expressed in cells of the innermost (antrally located) granulosa
      compartment up to and after the point of ovulation. Based on the inferred
      biological properties of CTGF protein and the spatiotemporal pattern of CTGF mRNA
      expression in the ovary, we postulate roles for ovarian CTGF during early stages
      of follicular development and after ovulation in the formation of the corpus
      luteum.

PMID- 11988309
TI  - Matrix remodeling in the ovary: regulation and functional role of the plasminogen
      activator and matrix metalloproteinase systems.
AB  - In each reproductive cycle, extensive tissue remodeling takes place in the ovary
      during follicular development, ovulation, formation and regression of corpus
      luteum (CL) and follicular atresia. Several lines of indirect evidence suggest
      that these changes are mediated, in part, by proteases belonging to the
      plasminogen activator (PA) and the matrix metalloproteinase (MMP) systems. These
      two enzyme systems include both proteinases and associated inhibitors, that are
      thought to act in concert via a cascade of proteolytic events, the end result of
      which is the generation of a broad spectrum proteolytic activity, that can
      mediate physiological tissue remodeling throughout the body. The current review
      highlights the key features of these two enzyme systems and focuses on their
      regulation and functional role during the dynamic remodeling processes that takes
      place in the ovary during each reproductive cycle.

PMID- 11988310
TI  - The prognostic value of metalloproteinases and angiogenic factors in ovarian
      carcinoma.
AB  - The objective of this study was to analyze the correlation between matrix
      metalloproteinases (MMPs) and angiogenic genes and survival in advanced-stage
      ovarian carcinomas. Primary and metastatic ovarian carcinomas from patients
      diagnosed with FIGO stage III-IV disease and followed up to 20 years were studied
      using mRNA in situ hybridization (ISH). Expression of MMP-2, MMP-9, membrane-type
      1-MMP (MT1-MMP), the MMP inhibitor TIMP-2, vascular endothelial growth factor
      (VEGF), interleukin-8 (IL-8) and basic fibroblast growth factor (bFGF) was
      studied. MMP-2, MMP-9 and TIMP-2 mRNA was detected in both tumor and stromal
      cells, while MT1-MMP was largely confined to tumor cells. In univariate analysis
      of primary tumors, TIMP-2 and MMP-9 mRNA expression correlated with poor outcome.
      In metastatic lesions, mRNA expression of TIMP-2, MMP-2, and MT1-MMP correlated
      with poor survival. In a multivariate analysis of primary tumors, TIMP-2
      expression in stromal cells (P=0.006) and MMP-9 expression in tumor cells
      (P=0.011) retained their predictive value. Intense expression of bFGF mRNA and
      weak expression of IL-8 mRNA was detected in both stromal and tumor cells in most
      cases, while VEGF mRNA expression was limited to a few cases. Angiogenic mRNA
      expression showed no correlation with disease outcome in survival analysis
      (P>0.05). We conclude that bFGF is the major angiogenic factor expressed in
      ovarian carcinoma at the mRNA level. MMP-2, MMP-9, MT1-MMP and TIMP-2 are valid
      markers of poor survival in advanced-stage ovarian carcinoma.

PMID- 11988311
TI  - Transgenic and knockout mouse models for the study of luteinizing hormone and
      luteinizing hormone receptor function.
AB  - The main functions of luteinizing hormone (LH) are concerned with regulation of
      gonadal function, and these functions are today well delineated through previous
      physiological studies. However, novel information of less well-known aspects of
      actions of this hormone is currently emerging from studies on genetically
      modified mouse models, with either enhanced or suppressed LH/LH receptor (LHR)
      function. The novel functions of LH include its role, in specific situations, as
      promoter of formation and growth of gonadal and extragonadal tumors. Chronically
      elevated LH levels in transgenic (TG) mice can also induce responses to this
      hormone in extragonadal tissues. The knockout (KO) mouse for the LHR has
      elucidated various less well-known details in the function of LH during ontogeny
      and adult life. Finally, studies on LHR promoter function have revealed that the
      expression of this gene occurs in age, sex and tissues-specific fashion. The
      purpose of this brief review is to summarize some of our recent findings upon
      studies of TG and KO mice with altered function of LH or its receptor.

PMID- 11988312
TI  - Consequences of targeted inactivation of LH receptors.
AB  - The inactivation of luteinizing hormone (LH) receptors was neither lethal nor it
      had any effect on sex differentiation. However, it dramatically reduced the
      growth and development of gonads and the reproductive tract. As a result, both
      female and male animals were infertile. Serum LH levels were dramatically
      elevated, follicle stimulating hormone (FSH) levels moderately elevated in both
      sexes, estradiol and progesterone levels partially decreased in females,
      testosterone levels dramatically decreased and estradiol levels moderately
      increased in males. The knockout of LH receptors had no effect on gonadal FSH
      receptors in both sexes, progesterone receptors in females and androgen receptors
      in males. However, estrogen receptor ERalpha and steroidogenic acute regulatory
      protein decreased and ERbeta increased in both sexes. cDNA expression array
      analyses revealed that testes were affected more than ovaries and more genes
      showed an increase rather than a decrease in testes. The affected genes came from
      many unexpected families. Both null females and males had a decreased density of
      femur and became obese with age. The ovarian failure in knockout animals could
      not be reversed by estradiol/progesterone replacement therapy or by PMSG and
      human chorionic gonadotropin (hCG) injections. Although, testosterone replacement
      therapy of 30-60-day old null males partially improved spermatogenesis, the
      animals still remained infertile. A single testosterone injection on postnatal
      day 1 followed by 21-45-day testosterone replacement therapy beginning at 30 days
      of age, however, restored fertility. Studies showed that uterus of null animals
      could not initiate pregnancy even though the size and morphology were greatly
      improved by estradiol and progesterone replacement therapy. In general, non
      gonadal phenotypes in null females and males were not completely reversed by
      hormone replacement therapy, suggesting that LH signaling could be important for
      their function. Heterozygous animals were indistinguishable from wild-type
      animals at 60 days of age. However, as they grew to about 1 year of age, they
      began to stop cycling, some became extremely obese, showed a decreased density of
      femur and all animals developed endometrial tumors with a cancer histology. LH
      receptor-knockout animals will be useful in advancing our present understanding
      on the importance of classical as well as non-classical actions of LH in the
      body, in advancing novel therapeutic uses of hCG, and in better understanding and
      rationalizing the consequences of inactivating type human LH receptor mutations.

PMID- 11988313
TI  - Mechanisms of gonadotropin desensitization.
AB  - The gonadotropic hormones, FSH and LH exert a major effect on ovarian and
      testicular function through interaction with specific seven-transmembrane domain
      glycoprotein receptors. Desensitization to the hormones, which can occur both in
      vivo and in vitro, is essential for prevention of overstimulation of the gonadal
      cells. The long-term process of desensitization to the gonadotropic hormones is
      probably mediated, in part, by extensive clustering and internalization of the
      hormone-receptor complex. Short-term desensitization may occur as a result of
      phosphorylation of serine or threonine residues on the receptor molecules,
      although a specific receptor kinase has not yet been identified. Recently, we
      have discovered a novel mechanism of gonadotropin desensitization, which is
      exerted by down-regulation of StAR expression and steroidogenesis mediated by
      MAPK activation as a result of hormone-receptor interaction, cAMP accumulation
      and PKA activation. Thus, PKA not only mediates gonadotropin-induced
      steroidogenesis, it also activates the down-regulation mechanism that can silence
      steroidogenesis under certain conditions. Moreover, our findings raise the
      possibility that activation or inhibition of ERK by other pathways could be an
      important mechanism for diminution or amplification of gonadotropin-stimulated
      steroidogenesis. This could contribute to functional luteolysis, a process in
      which luteinized granulosa cells show reduced sensitivity to LH despite
      maintenance of LH receptors, or to up-regulation of the steroidogenic machinery
      during luteinization of granulosa cells.

PMID- 11988314
TI  - New trends in gamete's cryopreservation.
AB  - We developed new techniques to improve freezing and vitrification of sperm,
      oocytes and embryos. Our novel freezing technology is based on 'Multi-Thermal
      Gradient' (MTG) freezing that is used for sperm. The freezing apparatus has the
      ability to control ice crystals propagation by changing thermal gradient or the
      liquid-ice interface velocity which optimizes ice crystals morphology during
      freezing of cells and tissue. Using this apparatus we were able to freeze bull,
      stallion, boar, ram, fowl and human sperm with normal post-thaw motility/pre
      freezing motility of 70-100%. The vitrification method includes the cooling of
      nanoliter sample (the 'Minimum Drop Size' technique) in 'super-cooled' liquid
      nitrogen (-210 degrees C), which maximized cooling rate to the highest physically
      possible (24-130000 degrees C/min). Using this method we achieved very high
      survival of bovine oocytes and embryos. Vitrification of oocytes at the MII stage
      resulted with cleavage and blastocyst rate of 50 and 20%, respectively. The
      vitrification of in-vitro production (IVP) of bovine embryos allowed the
      production of a healthy calf after embryo-transfer carrying the name 'Zegugit'
      (in Hebrew: made from glass).

PMID- 11988315
TI  - Protecting female fertility from cancer therapy.
AB  - Recent advances in cancer therapy have improved the long-term survival of young
      cancer patients who are then commonly faced with iatrogenic infertility and
      premature ovarian failure. Preservation of fertility potential has thus become a
      major goal and could be realized by preventing ovarian toxicity or by
      cryopreservation of reproductive cells (i.e. oocytes, embryos) and tissues (i.e.
      ovarian cortex). GnRH analogs prevent chemotherapy-induced-ovarian-damage in
      rats, however human results are controversial. Anti-apoptotic agents (i.e.
      sphingosine-1-phosphate) may present an innovative treatment to prevent oocyte
      destruction during cancer therapy. Although cryopreservation of mouse oocytes is
      successful, the results obtained in other mammalian species were worse, probably
      due to their extreme sensitivity to suboptimal conditions during the process of
      cryopreservation. This resulted in low oocyte survival and fertilization rates, a
      high incidence of polyploidy, and poor embryonic developmental ability. Ovarian
      tissue cryopreservation is currently considered as the optimal procedure for
      follicle banking. Transplantation offers the best prospect of using frozen-thawed
      ovarian tissue, since no reliable ovarian in-vitro culture technology exists.

PMID- 11988316
TI  - Preservation of fertility and ovarian function and minimalization of chemotherapy
      associated gonadotoxicity and premature ovarian failure: the role of inhibin-A
      and -B as markers.
AB  - BACKGROUND: Following the improved long term survival in young women with
      lymphoma and leukemia undergoing chemotherapy, the preservation of future
      fertility has been the focus of recent interest. The investigational endeavors of
      ovarian cryopreservation awaits the clinical experience of in-vitro maturation of
      thawed primordial follicles, their in-vitro fertilization and ET. Although
      promising, this experience is not available yet. Moreover, the risk of possible
      reimplantation of malignant stem cells with the thawed cryopreserved ovary has
      been raised, following experimental animal observations. Therefore, until these
      innovative endeavors prove successful, and in parallel to them we attempted to
      minimize the gonadotoxic effect of chemotherapy by the co-treatment with a GnRH
      agonistic analogue to induce a temporary prepubertal milieu. Whereas, inhibin-B
      concentrations in serum may reflect the ovarian granulosa cell compartment,
      inhibin-A reflects luteal function. The immunoreactive inhibin-A and -B in these
      patients, before, during, and following the gonadotoxic chemotherapy were
      measured. METHODS: A prospective clinical protocol was undertaken in 55 women
      with lymphoma, aged 15-40 years, ten with leukemia and eight undergoing
      chemotherapeutic treatments for non malignant diseases such as systemic lupus
      erythematosus (SLE) or other autoimmune diseases. A monthly injection of depot D
      TRP6-GnRH-a was administered from before starting the chemotherapy until its
      conclusion, up to a maximum of 6 months. Hormonal profile (FSH, LH, E2, T, P4,
      IGF-1, IGF-BP3, and PRL) was taken before starting the GnRH-a/chemotherapy co
      treatment, and monthly thereafter, until resuming spontaneous ovulation. This
      group was compared with a control group of 55 women who have been treated with
      similar chemotherapy. Inhibin-A and -B immunoactivity was measured by an ELISA
      commercial kit (Serotec). RESULTS: Whereas, all but three (40- and 36-year-old)
      of the surviving patients with GnRH-a/chemotherapy co-treatment group resumed
      spontaneous ovulation and menses within 12 months, less than half of the patients
      in the control group (chemotherapy without GnRH-a co-treatment) resumed ovarian
      function and regular cyclic activity (P<0.05). The remaining 56% experienced
      premature ovarian failure (POF). Temporary increased FSH concentrations were
      experienced by about a third of the patients resuming cyclic ovarian function,
      suggesting a reversible ovarian damage in a larger proportion of women than those
      experiencing POF. Inhibin-A and -B decreased during the GnRH-a/chemotherapy co
      treatment but increased to normal levels in patients who resumed regular ovarian
      cyclicity, and/or spontaneously conceived, as compared with low levels in those
      who developed POF. CONCLUSIONS: If these preliminary data are consistent in a
      larger group of patients, inhibin-A or -B concentrations may serve as prognostic
      factors for predicting the resumption of ovarian function, in addition to the
      levels of FSH, LH and E2. The GnRH-a co-treatment should be considered in every
      woman in the reproductive age receiving chemotherapy, in addition to ART, and to
      the investigational attempts of ovarian cryopreservation for future in-vitro
      maturation, autotransplantation, or xenotransplantation.

PMID- 11988317
TI  - Spermatogonial stem cell preservation and transplantation.
AB  - Spermatogonia are the male germ line stem cells. Their life long expansion is
      needed for permanent production of male germ cells. Spermatogonia are the only
      cells of the germ line, which proliferate in adulthood and offer interesting
      applications as they are potentially totipotent and immortal cells. This review
      presents some of the recent breakthroughs, which have led to a better
      understanding of spermatogonial physiology and opened new fields of basic
      research and of clinical applications in veterinary and medical science.

PMID- 11988318
TI  - The expanding family of CREB/CREM transcription factors that are involved with
      spermatogenesis.
AB  - One of the molecular mechanisms shown to have played a major role in
      orchestrating the expression of the many genes with unique cellular and temporal
      specificity in spermatogenesis, is the cAMP-dependent signaling pathway. In this
      pathway, gene expression is mediated primarily by two members of the bZIP
      transcription factors-cAMP-response element binding protein (CREB) and cAMP
      responsive element modulator (CREM). Both bind a specific cis element, cAMP
      response element (CRE), in the promoter of target genes, both are activated by
      protein kinase A (PKA) phosphorylation that enables binding of CREB binding
      protein (CBP) and recruitment of the basal transcription machinery, and both are
      characterized by multiple alternatively spliced forms. Some of these
      alternatively spliced forms lack the transactivation domains and hence function
      as transcription suppressors. In Sertoli cells, CREB levels fluctuate in a
      cyclical manner that depends on the specific cell associations along the
      spermatogenic wave. Follicle stimulating hormone (FSH) activates the cAMP
      signaling pathway and consequently, CREB positively auto-regulates its own
      expression (by binding to a CRE like element in its promoter). Subsequently,
      activated CREB activates transcription of genes essential for proper germ cell
      differentiation. In addition, TNFalpha secreted by round spermatids, activates NF
      kappaB dependent CREB expression in Sertoli cells and thus, contributes to the
      elevated CREB levels as long as these cells are intimately associated. Inducible
      cAMP early repressor (ICER), a suppressor isoform of CREM, also activated by
      CREB, down regulates CREB expression together with its own expression, resetting
      CREB to basal level that enables a new spermatogenic wave. In germ cells,
      antagonist forms of CREM (alpha, beta and gamma) are present in premeiotic cells
      and early prophase spermatocytes. A prominent switch to the CREMtau and
      CREMtheta; activating forms starts in pachytene spermatocytes leading to the
      activation of haploid genes important for spermiogenesis in round spermatids.
      Interestingly, in germ cells, CREM exerts activation of haploid genes independent
      of its phosphorylation state. It associates with activator of CREM in testis
      (ACT), that has an intrinsic transcriptional activity, rather than with CBP.
      These and other findings suggest that the expanding CREB/CREM proteins and
      potentially other members of the CREB family are key molecular regulators at all
      stages of spermatogenesis.

PMID- 11988319
TI  - Involvement of intratesticular IL-1 system in the regulation of Sertoli cell
      functions.
AB  - The Interleukin-1 (IL-1) system has been suggested to be involved in the cell
      cell cross talk within the testis. To investigate the testicular autocrine,
      paracrine and endocrine factors involved in the regulation of Sertoli cell
      functions, we have examined the capacity of Sertoli cell cultures, from immature
      mice, to produce IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1ra) under
      in vitro cultures and in the presence of testicular physiological and
      pathological factors. Our investigation revealed that Sertoli cells produce large
      amounts of IL-1alpha, IL-1ra but not IL-1beta under basal culture conditions, as
      examined by ELISA and immunohistochemical staining. Liposaccharides (LPS), as
      well as IL-1alpha and IL-1beta were found to stimulate IL-1alpha and IL-1ra, but
      not IL-1beta production, in Sertoli cells from immature mice. Maximum
      concentration of IL-1alpha and of IL-1ra was observed after 2 and 8 h after the
      stimulation, respectively. The addition of IL-1ra to Sertoli cells did not alter
      their capacity to constitutively produce IL-1alpha. However, the stimulatory
      effects of recombinant IL-1alpha on IL-1alpha production by Sertoli cells were
      reversed by the concomitant addition of recombinant IL-1ra. FSH is capable to
      induce IL-1ra production in Sertoli cells in a dose-dependent manner but not IL
      1alpha or IL-1beta. As expected, Sertoli cell cultures were also shown to
      constitutively secrete transferrin. Stimulation of these cultures with IL-1alpha,
      IL-1beta significantly increased their capacity to secrete transferrin. Addition
      of IL-1ra to unstimulated Sertoli cell cultures did not affect their capacity to
      secrete transferrin. Stimulation of Sertoli cell cultures with a combination of
      both IL-1alpha and FSH or IL-1beta and FSH showed additive effect between IL-1
      and FSH in their capacity to induce transferrin secretion by these cells.
      However, stimulation of Sertoli cells with a combination of both IL-1ra and FSH
      did not affect their capacity to secrete transferrin as compared with FSH
      stimulated cultures. Our results with Sertoli cells, in addition to previous data
      on Lydig cell and germ cells, may suggest the involvement of the IL-1 system in
      testicular paracrine/autocrine regulation, which could be involved in the
      regulation of spermatogenesis and spermiogenesis processes and male fertility.

PMID- 11988320
TI  - Bypassing natural sperm selection during fertilization: the azh mutant offspring
      experience and the alternative of spermiogenesis in vitro.
AB  - Molecular aspects of spermiogenesis can be studied using mouse mutants and
      spermatids developed in vitro. The azh/azh mutant is an attractive model system
      because structural abnormalities in the sperm head and the ectopic position of
      the manchette are associated with tail bending and looping. Spermatids,
      developing an axoneme in vitro and capable of cell motility, offer the
      possibility of the dynamic analysis of tail development. Offspring generated by
      intracytoplasmic injection of azh/azh sperm heads into normal mouse oocytes
      complement the mouse mutant approach. A central question of sperm tail
      development is the role of the manchette, a transient microtubular structure
      assembled soon after the organization of the axoneme. The fractionation of intact
      manchettes by gradient centrifugation has enabled a biochemical analysis of
      constitutive tubulin isotypes and transiently associated proteins. For example,
      keratins Sak57, Odf1, and Odf2 are initially stored in the manchette before being
      sorted to the outer dense fibers and fibrous sheath of the developing spermatid
      tail. Additional proteins associated with the manchette include two proteases,
      the 26S proteasome and N-arginine convertase (both sorted to the developing
      spermatid tail), a spermatid perinuclear RNA binding protein, Spag4, an Odf1
      binding protein, and type 4 cAMP-specific phosphodiesterase D. Keratin 9 and
      delta-tubulin are two proteins found in the perinuclear ring of the manchette,
      the insertion site of the microtubular mantle. Available data indicate that the
      manchette is a highly dynamic structure providing microtubular tracks to
      structural proteins participating in the sperm tail development.

PMID- 11988321
TI  - Intracellular calcium regulation in sperm capacitation and acrosomal reaction.
AB  - Binding to the egg's zona pellucida stimulates the spermatozoon to undergo
      acrosome reaction, a process which enables the sperm to penetrate the egg. Prior
      to this binding, the spermatozoa undergo in the female reproductive tract a
      series of biochemical transformations, collectively called capacitation. The
      first event in capacitation is the elevation of intracellular calcium and
      bicarbonate to activate adenylyl cyclase (AC) to produce cyclic-AMP, which
      activates protein kinase A (PKA) to phosphorylate certain proteins. During
      capacitation, there is also an increase in actin polymerization and in the
      membrane-bound phospholipase C (PLC). Sperm binding to zona-pellucida causes
      further activation of cAMP/PKA and protein kinase C (PKC), respectively. PKC
      opens a calcium channel in the plasma membrane. PKA together with inositol
      trisphosphate activate calcium channels in the outer acrosomal membrane, which
      leads to an increase in cytosolic calcium. The depletion of calcium in the
      acrosome will activate a store-operated calcium entry mechanism in the plasma
      membrane, leading to a higher increase in cytosolic calcium, resulting in
      membrane fusion and acrosome reaction.

PMID- 11988322
TI  - Signalling in mammalian egg activation: role of protein kinases.
AB  - Embryonic development is initiated after the fertilizing spermatozoon enters the
      egg and triggers a process known as 'egg activation'. Activation results in an
      increase in intracellular calcium concentration, cortical granule exocytosis
      (CGE), cell cycle resumption and recruitment of maternal mRNA. Various treatments
      can induce parthenogenetic activation characterized by the same manifestations.
      Signal transduction pathways similar to those known for somatic cells mediate the
      mammalian egg activation. This review focuses on the signal transduction pathways
      that occur during mammalian fertilization and during parthenogenetic egg
      activation. We discuss the possibility that members of the protein tyrosine
      kinase (PTKs) families, the Src family PTKs in particular, operate during egg
      activation and that protein kinase C can induce CGE.

PMID- 11988323
TI  - Role of cyclic nucleotide signaling in oocyte maturation.
AB  - The development of the ovarian follicle, oocyte maturation, and ovulation require
      a complex set of endocrine, paracrine, and autocrine inputs that are translated
      into the regulation of cyclic nucleotide levels. Changes in intracellular cAMP
      mediate the gonadotropin regulation of granulosa and theca cell functions.
      Likewise, a decrease in cAMP concentration in the oocyte has been associated with
      the resumption of meiosis. Using pharmacological and molecular approaches, we
      determined that the expression of cyclic nucleotide phosphodiesterases (PDEs),
      the enzymes that degrade and inactivate cAMP, is compartmentalized in the ovarian
      follicle of all species studied, with PDE3 present in the oocytes and PDE4s in
      granulosa cells. The PDE3 expressed in the mouse oocyte was cloned, and the
      protein expressed in a heterologous system had properties similar to those of a
      PDE3A derived from somatic cells. Inhibition of the oocyte PDE3 completely
      blocked oocyte maturation in vitro and in vivo, demonstrating that the activity
      of this enzyme is essential for oocyte maturation. Heterologous expression of
      PDE3A in Xenopus oocyte causes morphological changes distinctive of resumption of
      meiosis (GVBD), as well as activation of mos translation and MAPK
      phosphorylation. Using mRNA and antibody microinjection in the Xenopus eggs, we
      have shown that PDE3 is downstream from the kinase PKB/Akt in the pathway that
      mediates IGF-1 but not progesterone-induced meiotic resumption. The presence of a
      similar regulatory module in mammalian oocytes is inferred by pharmacological
      studies with PDE3 inhibitors and measurement of PDE activity. Thus, PDE3 plays an
      essential role in the signaling pathway that controls resumption of meiosis in
      amphibians and mammals. Understanding the regulation of this enzyme may shed some
      light on the signals that trigger oocyte maturation.

PMID- 11988324
TI  - Translational and post-translational modifications in meiosis of the mammalian
      oocyte.
AB  - The fully-grown oocyte is transcriptionally inactive. Therefore, translational
      and post-translational modifications furnish the control mechanism of key
      components governing meiosis. Regulation by protein synthesis provides an
      irreversible unidirectional mechanism for an extended period that can be
      restricted by a complementary degradation of the same protein. Both processes
      utilize tight measures to ensure precise expression at the right time in the
      right place. Rapid modifications such as phosphorylation and dephosphorylation
      supply reversible means to regulate protein action. Information regarding these
      extremely exciting issues is being accumulated recently in an exponential rate.
      However, the vast majority of these data is generated from studies conducted on
      Xenopus oocytes. We fully agree with Andrew Murray's statement that "The modern
      trend of promoting research on a small number of 'model' organisms will
      eventually deprive us of the opportunity to study interesting biology" [Cell 92
      (1992) 157]. Thus, despite of the enormous technical difficulties resulting from
      the limited availability of biological material we extended our interest to
      mammalian model systems. Our review will attend to certain examples of such
      modifications in the regulatory pathway of meiosis in mammalian oocytes.

PMID- 11988325
TI  - The mechanism of CSF arrest in vertebrate oocytes.
AB  - A cytoplasmic activity in mature oocytes responsible for second meiotic metaphase
      arrest was identified over 30 years ago in amphibian oocytes. In Xenopus oocytes
      cytostatic factor (CSF) activity is initiated by the progesterone-dependent
      synthesis of Mos, a MAPK kinase kinase that activates the MAPK pathway. CSF
      arrest is mediated by a sole MAPK target, the protein kinase p90(Rsk). Rsk
      phosphorylates and activates the Bub1 protein kinase, which may cause metaphase
      arrest due to inhibition of the anaphase-promoting complex (APC) by a conserved
      mechanism defined genetically in yeast and mammalian cells. CSF arrest in
      vertebrate oocytes by p90(Rsk) provides a link between the MAPK pathway and the
      spindle assembly checkpoint in the cell cycle.

PMID- 11988326
TI  - Lanosterol 14alpha-demethylase and MAS sterols in mammalian gametogenesis.
AB  - The lanosterol 14alpha-demethylase protein complex is composed of a cytochrome
      P450 enzyme CYP51 and its redox partner NADPH cytochrome P450 reductase. The
      complex participates in cholesterol biosynthesis and produces folicular fluid
      meiosis activating sterol (FF-MAS) from lanosterol. FF-MAS is metabolized further
      by sterol Delta14-reductase to testis-meiosis activating sterol (T-MAS).
      Additional enzymatic steps are needed before cholesterol is produced. Using the
      anti-human CYP51 antibody we have studied CYP51 protein expression by confocal
      microscopy in male and female mouse gonads. Leydig cells and acrosomes of
      spermatids express the highest levels of the CYP51 protein. CYP51 protein is also
      detected in primary mouse oocytes of non-treated mice and in some granulosa
      cells. While regulatory mechanisms responsible for FF-MAS accumulation in the
      ovary are not yet established, two mechanisms contributing to production the of T
      MAS in the testis have been found. Potential in vivo roles of FF-MAS and T-MAS in
      fertilization are discussed.

PMID- 11988327
TI  - Role of meiosis activating sterols, MAS, in induced oocyte maturation.
AB  - Meiosis of follicle enclosed oocytes is maintained in the prophase of the first
      meiotic division and oocytes do not spontaneously resume meiosis during oocyte
      growth and follicle development. Arrest of the meiotic process is most likely
      secured by the presence of follicular purines, e.g. hypoxanthine, which maintain
      high levels of cAMP in the oocyte and which also in vitro prevent oocytes from
      resuming meiosis. Only in response to the mid-cycle surge of gonadotropins will
      oocytes of preovulatory follicles overcome the meiosis arresting effect of
      hypoxanthine and resume meiosis proceeding to the metaphase of the second meiotic
      division. Morphologically, resumption of meiosis is observed by the disappearance
      of the oocyte's nuclear membrane (germinal vesicle), a process called germinal
      vesicle breakdown (GVB). The molecular mechanism down-stream to receptor
      activation by which the mid-cycle surge of gonadotropins induces oocytes to
      resume meiosis is, however, only partly understood. The oocyte itself lacks
      gonadotropin receptors and its action is mediated through the attached cumulus
      cells. In vitro it has been shown that FSH induces synthesis of a signal in the
      cumulus cells, which overcomes the meiosis arresting effect of hypoxanthine. We
      have shown that a group of sterols, meiosis activating sterols (MAS), induces
      oocyte maturation in vitro even in oocytes depleted of cumulus cells. MAS were
      identified as intermediates in the cholesterol biosynthesis between lanosterol
      and cholesterol. The two best characterized members of the MAS family are FF-MAS
      purified from human follicular fluid (4,4-dimethyl-5alpha-cholest-8,14,24-triene
      3beta-ol) and T-MAS purified from bull testicular tissue (4,4-dimethyl-5alpha
      cholest-8,24-diene-3beta-ol). The synthesis, quantification, localization and
      tissue-accumulation of MAS are reviewed. Several publications have documented the
      pharmacological effect of MAS in different species, including oocytes from mouse,
      rat and human. Conflicting results obtained by the use of sterol synthesis
      inhibitors, which prevent MAS-accumulation, are also discussed. Whether FSH
      actually uses MAS as a signal transduction molecule for inducing oocyte
      maturation and the mechanism by which MAS induce resumption of meiosis is
      currently unknown, but data to support that MAS is part of the FSH induced signal
      transduction pathway are presented.

PMID- 11988328
TI  - Is meiosis activating sterol (MAS) an obligatory mediator of meiotic resumption
      in mammals.
AB  - In-vitro studies of mouse oocytes have provided evidence that two closely related
      sterols, subsequently named meiosis-activating sterols (MAS), can overcome the
      inhibitory effect of hypoxanthine on resumption of meiosis. These sterols are
      synthesized by cytochrome P450 (CYP) lanosterol 14alpha-demethylase (LDM), a key
      enzyme in cholesterol biosynthesis. Our studies in the rat with specific
      inhibitors and molecular approaches did not support the hypothesis that MAS is an
      obligatory step in the stimulation of the resumption of meiosis. (i) Specific
      inhibitors of MAS synthesizing enzymes did not prevent spontaneous or LH
      stimulated meiosis at doses that have previously been shown to effectively
      suppress LDM activity. At higher doses, they caused degeneration of oocytes. (ii)
      The timing of LDM expression in the ovary was incompatible with a role for MAS in
      meiosis. (iii) The preferential localization of LDM protein in the oocytes
      suggests MAS production in oocytes, rather than its transport from the somatic
      compartment as expected by the suggested role of MAS in the regulation of meiosis
      as a putative cumulus-oocyte signal molecule. (iv) AY-9944, which supposedly
      increases MAS levels by inhibiting its metabolism, induced the maturation of
      follicle-enclosed oocytes that was much delayed as compared with gonadotropic
      stimulation. Thus, the resumption of meiosis induced by added MAS [Biol. Reprod.
      61 (1999) 1362, Biol. Reprod. 64 (2001) 418] or presumed endogenous MAS
      accumulation by AY-9944, resulted in oocyte maturation with remarkably slower
      kinetics than observed with LH stimulation. This delay in meiosis after MAS
      stimulation, the studies with LDM inhibitors and its spatial and temporal
      expression, cast serious doubts whether MAS is indeed mediating the meiosis
      inducing action of the gonadotropins, as suggested.

PMID- 11988329
TI  - Trophoblast functions, angiogenesis and remodeling of the maternal vasculature in
      the placenta.
AB  - One of the most important local adaptations to pregnancy is the change in
      maternal blood flow to the implantation site. In rodents and primates, new blood
      vessels form through angiogenesis, dilate and then become modified such that the
      blood enters into trophoblast cell-lined sinuses (hemochorial). Evidence from
      gene knockout mice suggests that factors from the placenta regulate the uterine
      vasculature. Consistent with this, trophoblast giant cells produce a number of
      angiogenic and vasoactive substances that may mediate these effects.
      Teratocarcinomas containing large numbers of trophoblast giant cells (derived
      from Parp1 gene-deficient ES cells) show similar 'hemochorial' host blood flow,
      implying that the effects are not specific to the uterine vascular bed. As in
      primates, murine trophoblast cells also invade into the uterine arteries of the
      mother. However, in normal pregnancy, dilation of the uterine arteries may be
      largely mediated by the effect of uterine natural killer cells.

PMID- 11988330
TI  - The murine 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene family: a
      postulated role for 3beta-HSD VI during early pregnancy.
AB  - The enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is essential
      for the biosynthesis of all active steroid hormones. The 3beta-HSD enzyme
      consists in multiple isoforms, each the product of a distinct gene. In the mouse,
      six tissue-specific isoforms have been identified. These isoforms are expressed
      in a tissue- and temporal specific manner. Mouse 3beta-HSD VI is the only isoform
      expressed in decidua and giant trophoblast cells during the first half of mouse
      pregnancy. The tissue- and temporal-specific expression of 3beta-HSD VI during
      mouse pregnancy, as determined by in situ hybridization and immunohistochemistry,
      shows that 3beta-HSD is expressed exclusively in the antimesometrial decidua on
      E6.5 and E7.5. By E9.5, expression of 3beta-HSD is observed in giant trophoblast
      cells with a marked increase in expression by E10.5. No expression of 3beta-HSD
      is seen in decidua after E7.5 and no expression of 3beta-HSD is seen in the
      embryo at any of the times investigated. Giant trophoblast cells in culture from
      E9.5 and E10.5 synthesize progesterone with cells from E10.5 producing about 3.5
      fold more progesterone during the first 24 h in culture. Western blot analysis of
      3beta-HSD VI protein demonstrates that the amount of 3beta-HSD VI protein
      correlates with the amount of progesterone biosynthesis in giant trophoblast
      cells from E9.5 and E10.5. We propose that progesterone produced during the first
      half of mouse pregnancy in decidua and giant trophoblast cells acts as an
      immunosuppressant at the fetal maternal interface to prevent rejection of the
      fetus.

PMID- 11988331
TI  - Uterine and placental expression of steroidogenic genes during rodent pregnancy.
AB  - The ontogeny and functional role of steroidogenesis during mammalian gestation is
      poorly understood. This review provides a summary of our recent findings on the
      spatio-temporal expression of key steroidogenic genes controlling progesterone
      synthesis in the uterus during mouse pregnancy. We have shown that onset of
      cholesterol side chain cleavage cytochrome P450 (P450scc) and a newly identified
      isoform of murine 3beta-hydroxysteroid dehydrogenase/isomerase type VI (3betaHSD
      VI) expression occurs upon decidualization of the uterine wall induced by
      implantation. This unexpected early expression of the enzymes in the maternal
      decidua is terminated at mid-pregnancy when the steroidogenic ability reappears
      in the extraembryonic giant cells at the time of placentation. The giant cells
      express another protein indispensable for steroid hormone synthesis in the
      adrenal and gonads, Steroidogenic Acute Regulatory (StAR) protein. Unlike the
      human placenta, the steroidogenic genes are not expressed in the cells of the
      mature mouse placenta during the second half of gestation. Finally, our studies
      suggest that transcriptional regulation of P450scc is mediated by a non-SF-1
      protein that substitutes SF-1 functions in the extraembryonic cells.
      Collectively, the results of the present study suggest that, during early phases
      of pregnancy, local progesterone synthesis in the maternal decidua and the
      trophoblast layers surrounding the embryonal cavity is important for successful
      implantation and/or maintenance of pregnancy. We propose that the local
      production of progesterone acts as an immunosuppressant at the maternofetal
      interface preventing the rejection of the fetal allograft.

PMID- 11988332
TI  - Regulation of trophoblast invasion: from normal implantation to pre-eclampsia.
AB  - Conversion of the maternal spiral arteries into larger competent vessels is one
      of the essential steps in the development of the normal placenta. This process is
      apparently dependent on the invasion by trophoblasts of the sub-endometrial area
      and the spiral arteries. Preeclampsia is characterized by shallow trophoblast
      invasion and unconverted narrow spiral arteries. This leads to fetal hypoxia that
      causes endothelial injury that eventually manifest as maternal hypertension,
      edema, and proteinuria. The following steps have been shown to be involved in the
      breakthrough of the trophoblasts from the uterine cavity into the decidua and the
      spiral arteries: trophoblast targeting, adhesion, and detachment from the
      extracellular matrix (ECM), invasion of the ECM and maternal vessels by
      proteolysis. Abnormal expression and activity of these molecules may explain in
      part some of the molecular mechanisms leading to abnormal placentation and the
      development of preeclampsia.

PMID- 11988333
TI  - Cloning: experience from the mouse and other animals.
AB  - Cloning mammals has been successful for many years by splitting an early embryo
      or transferring embryonic cell nuclei into enucleated oocytes. Cloning is now
      possible with adult somatic cells. At present, cloning efficiency--as determined
      by the proportion of live offspring developed from all oocytes that received
      donor cell nuclei--is low regardless of the cell type (including, embryonic stem
      (ES) cells) and animal species used. In all animals, except of Japanese black
      beef cattle, the vast majority (>97%) of cloned embryos perish before reaching
      full term. Even in the Japanese cattle, less than 20% of cloned embryos reach the
      adulthood. This low efficiency of cloning seems to be due largely to faulty
      epigenetic reprogramming of donor cell nuclei after transfer into recipient
      oocytes. Cloned embryos with major epigenetic errors die before or soon after
      implantation. Those with relatively 'minor' epigenetic errors may survive birth
      and reach adulthood. We found that almost all fetuses of inbred mice die at birth
      from respiratory problems, while those of hybrid mice do not, suggesting that
      genomic heterogeneity masks-to some extent-faulty epigenetic errors. Thus far,
      the majority of cloned mice that survived birth, had a normal life span and were
      fertile. However, these animals may not be totally free of health problems.
      Postpubertal obesity in certain strains of mice is one example. A trial and error
      approach may discover better cells for cloning, but it would be wiser to
      understand the molecular mechanisms of epigenetic nuclear programming and
      reprogramming to find the way to make cloning safer and more efficient. The
      relatively high cloning success rate in the Japanese black cattle may provide us
      a clue of solving the problem of high mortality of cloned offspring.

PMID- 11988334
TI  - Effects of noradrenaline on cytosolic concentrations of Ca(2+) in cultured corpus
      cavernosum smooth muscle cells of the rabbit.
AB  - An immunohistochemical examination of cultured corpus cavernosum cells of the
      rabbit showed that they were composed of many smooth muscle cells retaining 
      smooth muscle actin and a few of endothelial cells. Application of noradrenaline
      (NA, 0.5-100 microM) to the culture dose-dependently increased cytosolic
      concentrations of Ca2+ ([Ca2+]i) in smooth muscle cells. The NA (10 microM)
      induced [Ca2+]i increase was dose-dependently inhibited by phenoxybenzamine (1 nM
      1 microM). The inhibition was 71% at 0.1 microM and was completely made at 1
      microM. An alpha(1)-adrenoceptor antagonist, prazosin (0.1 microM), inhibited the
      [Ca2+]i response by 42%, and propranolol (1 microM) enhanced the response by
      118%. These adrenoceptor antagonists showed almost the same effects on a
      contractile response of corporal tissue strips to NA (10 microM) as the effects
      on the [Ca2+]i response. Our results suggest that NA-induced [Ca2+]i increase was
      mixed with a large increase through 1-adrenoceptors and a small decrease through
      beta-adrenoceptors. The increased [Ca2+]i could play a role of intracellular
      messenger for leading to contraction of cavernosal smooth muscle cells.

PMID- 11988335
TI  - Focal encephalitis in the Lewis rat induced by intracerebral enterotoxin
      superantigen and amplified by activated intravenous splenocytes.
AB  - The histological response after intracerebral (IC) injection of superantigen
      (SAg) was investigated in unprimed Lewis rats. The staphylococcal enterotoxins
      (SE) A (SEA), and E, but not B or saline, induced a variable perivascular
      inflammation in the injected hemisphere (6.7 +/- 6.1 cuffs per tissue section
      with SEA; mean +/- SD). Adoptive transfer of mitogen activated splenocytes (AS)
      augmented the response to SEA significantly (18.5 +/- 11.4; P<0.05). With or
      without AS transient bilateral perivascular cuffs were observed around the
      ventricles and in the corpus callosum up to 3 days after IC injection. The
      findings demonstrate that local expression of SAg in the brain can cause
      encephalitis, depending on the number of activated T cells in the circulation.

PMID- 11988336
TI  - Effect of repeated administration of morphine on the activity of extracellular
      signal regulated kinase in the mouse brain.
AB  - The present study was designed to determine whether chronic morphine treatment
      could influence the activity of extracellular signal regulated kinase (ERK) in
      the mouse brain. The single subcutaneous injection of morphine produced profound
      antinociception and an increase in phosphorylated-ERK (p-ERK) immunoreactivity in
      the pons/medulla, and these effects were blocked by a mu-opioid receptor
      antagonist, naloxone. The potency of antinociception induced by the second
      morphine injection at 24 h after the first morphine injection was similar to that
      by the first morphine injection. The p-ERK immunoreactivity in the pons/medulla
      obtained at 24 h after a single injection of morphine was not different from the
      control level. Repeated morphine injection once a day for 7 days resulted in a
      marked reduction of antinociception by morphine. The p-ERK immunoreactivity in
      the pons/medulla increased remarkably after 7 days repeated morphine injection.
      These data suggest that the sustained activation of ERK activity be associated
      with the development of antinociceptive tolerance to morphine in mice.

PMID- 11988337
TI  - Gene expression of D-amino acid oxidase in cultured rat astrocytes: regional and
      cell type specific expression.
AB  - Neuromodulative free D-serine is present in mammalian brain, and localized to
      type-2 astrocytes in culture. D-amino acid oxidase (DAO) is a flavoenzyme that
      catalyzes D-amino acids. We examined the DAO gene expression in cultured rat
      astrocytes by reverse transcriptase-polymerase chain reaction. We established a
      method to prepare highly purified culture of type-1 and type-2 astrocytes from
      any brain region. This method utilizes combination of cell type specific
      separation by shaking and subsequent purification by immunopanning or treatment
      with cytosine arabinoside. We detected higher DAO gene expression in type-1
      astrocyte cultures from cerebellum than that from cerebral cortex. In cerebellum,
      we observed higher DAO expression in type-1 astrocyte cultures than that in type
      2. We also revealed that DAO expression in C6, corresponding to type-1 astrocyte,
      was higher than that in CG-4 derived type-2 astrocytes.

PMID- 11988338
TI  - Decreased hemispheric Aquaporin-4 is linked to evolving brain edema following
      controlled cortical impact injury in rats.
AB  - The cerebral Aquaporin-4 (AQP4) water channel is suggested to be involved in
      brain edema formation aggravated by reduced cerebral blood flow early after
      traumatic brain injury (TBI). Therefore, the temporal profile of brain edema
      formation, AQP4 expression, and cortical perfusion were investigated following
      focal TBI in rats. Brain edema was maximal by 24 h. Concurrently, AQP4 protein
      expression was decreased in both hemispheres, being more pronounced in the
      traumatized hemisphere (-50%) 48 h after trauma. Cortical perfusion was only
      decreased in the ipsilateral cortex (-40%) between 4 and 8 h after trauma,
      reaching baseline values at 24 h. Globally reduced AQP4 expression following
      induction of a focal contusion coincides with edema development and seems to be
      independent of changes in cortical perfusion.

PMID- 11988339
TI  - Neurofibrillary tangles in elderly patients with late onset schizophrenia.
AB  - The objective of the present study was to examine whether neurofibrillary tangles
      densities are increased in elderly patients with late-onset schizophrenia (LOS).
      A neuropathological examination was performed in 32 consecutive autopsy brain
      specimens of ten patients with early-onset schizophrenia (EOS; onset of symptoms
      before the age of 40 years), eight patients with LOS (onset of symptoms after the
      age of 40 years) and 14 age-matched controls with no known neuropsychiatric
      disorder. Neurofibrillary tangle densities observed in the CA1 field of the
      hippocampus, the enthorhinal cortex, and the inferior temporal cortex in patients
      with LOS, EOS, and controls were not significantly different. All patients with
      EOS or LOS had Braak stages of III or less, which may correspond to normal aging.
      Thus, patients with schizophrenia, regardless of the age of onset of their
      symptoms, are no more prone to the development of Alzheimer's disease than the
      general population.

PMID- 11988340
TI  - A polymorphism within intron 11 of the tau gene is not increased in frequency in
      patients with sporadic Alzheimer's disease, nor does it influence the extent of
      tau pathology in the brain.
AB  - There are numerous polymorphisms within the tau gene but these are in complete
      linkage disequilibrium and exist as two common extended haplotypes H1 and H2. We
      have investigated the frequency of these haplotypes in 83 cases of sporadic
      Alzheimer's disease (AD) using the +34 polymorphism in intron 11 of the tau gene
      as a marker of H1 and H2 haplotypes. The total amount of hyperphosphorylated tau
      protein (tau load), present as neurofibrillary tangles, neuropil threads or
      plaque neurites, was quantified in the frontal cortex of these patients and
      related to tau haplotype. We found no increase in H1H1 haplotype in this autopsy
      population of cases with AD compared to published control data. Stratification of
      cases for apolipoprotein E (APO E) genotype showed a slight, but not
      statistically significant, overrepresentation of epsilon 4 allele amongst bearers
      of H2 haplotype. There were no overall differences in tau load between haplotype
      groups though cases within each haplotype group bearing APO E epsilon 4 allele
      had a significantly higher tau load than those without epsilon 4 allele. Neither
      age at onset or duration of illness differed according to tau haplotype. We
      conclude that the frequency of tau gene H1 haplotype is not elevated in AD and
      possession of this has no impact upon the amount of tau pathology in AD.

PMID- 11988341
TI  - Inhibition of glial glutamate transporter GLT-1 augments brain edema after
      transient focal cerebral ischemia in mice.
AB  - Excessively released glutamate is neurotoxic. Glutamate transporters maintain the
      extracellular level of glutamate by uptake into glia or neurons. We examined the
      role of GLT-1, a glial glutamate transporter, in brain damage resulting from
      transient focal ischemia in mice. Heterozygous gene deletion of GLT-1
      significantly augmented brain swelling resulting from 1 h of middle cerebral
      artery occlusion and 24 h reperfusion. In addition, this gene deletion
      significantly increased brain water contents in ischemic hemisphere at 6 h after
      reperfusion. Moreover, intraperitoneal injection of dihydrokainate (10 mg/kg), a
      specific inhibitor of GLT-1, augmented brain swelling. These data suggest that
      GLT-1 limits brain edema resulting from ischemia.

PMID- 11988342
TI  - The interplay between theta and alpha oscillations in the human
      electroencephalogram reflects the transfer of information between memory systems.
AB  - The exchange of information between the working and long-term memory system (WMS
      and LTMS) was investigated. We analyzed evoked theta and upper alpha
      desynchronization in a special memory task, designed to study the transfer of
      information between both memory systems. The results show that during attempts to
      retrieve information from the LTMS, evoked theta oscillations spread from
      anterior to posterior recording sites. When information actually is retrieved,
      the direction reverses and theta spreads to frontal sites. This time point--when
      direction reverses--varies between subjects to a large extent but is
      significantly correlated with memory performance and the onset of upper alpha
      desynchronization. We conclude that this phenomenon reflects the transfer of
      information between the WMS and LTMS

PMID- 11988343
TI  - A new pneumatic vibrator for functional magnetic resonance imaging of the human
      sensorimotor cortex.
AB  - The aim of the study was to implement a vibrotactile stimulator using functional
      magnetic resonance imaging (fMRI). A fMRI compatible vibration device consisting
      of a pneumatically driven dual membrane pump was developed. Brain activation
      during 50 Hz vibrotactile stimulation of the right hand-palm were compared to a
      right 2 Hz finger-to-thumb-tapping in ten healthy, right-handed male volunteers.
      The vibration paradigm showed a comparable activation pattern with respect to
      finger-to-thumb-tapping in the contralateral perirolandic region. The advantage
      of the new vibration device is the possibility to elicit the vibratory-tonic
      reflex due to the higher amplitude in context with the high frequency than
      established devices. This reflex is considered to be responsible for the
      activation in the primary motor cortex and the current paradigm might prove
      useful in future neurosurgical planning in patients with perirolandic lesions.

PMID- 11988344
TI  - Intensification of the development of ethanol dependence in mice lacking dopamine
      D(3) receptor.
AB  - The present study was designed to ascertain the role of dopamine D3 receptors in
      the development of physical dependence on ethanol using mice lacking the dopamine
      D3 receptor gene. The mutation eliminated the dopamine D3 receptor without any
      detectable changes in both dopamine D1 and D2 receptors. The ethanol-induced
      sleep time in dopamine D3 receptor knockout mice (D3-KO) was longer than that in
      wild-type mice. To examine the role of dopamine D3 receptors in the development
      of physical dependence on ethanol, two genotypes were chronically treated with 7%
      ethanol according to the liquid diet method. After the termination of ethanol
      treatment, severe withdrawal signs were observed in D3-KO mice as compared with
      wild-type mice. The present data suggest that the lack of dopamine D3 receptor
      genes in the mouse brain leads to the aggravation of the development of physical
      dependence on ethanol.

PMID- 11988345
TI  - Japanese encephalitis virus stimulates superoxide dismutase activity in rat glial
      cultures.
AB  - Japanese encephalitis virus (JEV) infection is commonly associated with
      inflammatory reaction and neurological disease that occurs in the infected
      animals. Reactive oxygen species have been implicated as a critical mediator for
      inflammation and diseases. The present study investigated the change of redox
      potential in glial cells following JEV infection. JEV infection induced the
      generation of superoxide anion and nitric oxide in rat cortical glial cells.
      Manganese superoxide dismutase, but not copper/zinc superoxide dismutase was
      activated by JEV infection, and this activation was blocked by pyrrolidine
      dithiocarbamate. In addition, the increased superoxide dismutase activity was
      also apparent in JEV acutely, or persistently infected continuous cell lines.
      These results suggest that cellular factors regulating oxidative pathway might
      play roles in responding to JEV infection.

PMID- 11988346
TI  - Adenosine 5'-triphosphate-evoked calcium responses in terminal Schwann cells of
      lanceolate sensory endings isolated from rat vibrissae.
AB  - Extracellular adenosine 5'-triphosphate (ATP) has been known to mediate and
      modulate cutaneous sensations. We examined the effect of this substance on
      isolated terminal Schwann cells associating with lanceolate endings, the
      mechanoreceptors of rat vibrissae. The free intracellular calcium concentration
      ([Ca(2+)](i)) of the sensory device was monitored by digital image microscopy in
      combination with a calcium-sensitive fluorescent probe, Fura-2. Application of
      ATP in concentrations raging from 10 microM to 1 mM evoked an increase in
      [Ca(2+)](i) in Schwann cell processes covering the lancet-like axon terminals as
      well as in round perikarya of the cells protruding from the terminals. In both
      portions, the ATP-evoked [Ca(2+)](i) elevations were slowly oscillatory at 10 and
      20 microM, and continuous at concentrations higher than 50 microM. Suramin 100
      microM blocked the effect of ATP. Uridine 5'-triphosphate was equipotent with
      ATP, while ,alpha,beta-methylene ATP was ineffective. These data indicate that
      the terminal Schwann cells express P2Y purinoceptors linked with the
      intracellular Ca(2+) signaling, and that this phenomenon is involved in the ATP
      mediated sensory modulation.

PMID- 11988347
TI  - A highly conserved tryptophane residue indispensable for cloned rat neuronal P2X
      receptor activation.
AB  - The role of a tryptophane residue (Trp(256)) in the extracellular loop of a
      neuronal P2X receptor clone (P2X(2) receptor/channel) was investigated using site
      directed mutagenesis and Xenopus oocyte expression. When Trp(256) was replaced
      with leucine, serine or phenylalanine (W256L, W256S or W256F), a current response
      to adenosine triphosphate (ATP) mediated through the P2X2 receptor/channel was
      abolished. When replaced with tyrosine (W256Y), the response was not abolished,
      but a reduced current response to ATP was observed. The insertion of a
      tryptophane residue in W256L at positions close to position 256 failed to recover
      the responsiveness to ATP. These results suggest that an amino acid residue with
      a side chain of an aromatic ring with a hydroxy group (tryptophane or tyrosine)
      is necessary exactly at position 256 for P2X(2) receptor/channel activation.

PMID- 11988348
TI  - Modification of a fiber protein in an adenovirus vector improves in vitro gene
      transfer efficiency to the mouse microglial cell line.
AB  - In microglia, it is difficult to introduce exogenous genes of interest even by
      recombinant adenovirus vectors (Ad) which can infect with high efficiency only to
      the cells expressing coxackievirus and adenovirus receptors (CAR). We found a
      lack of CAR expression in primary cultured murine microglia (PCMG) and its
      immortalized cell line MG5 by reverse transcription-polymerase chain reaction. In
      order to improve the efficiency of gene transfer, we generated a novel Ad (Ad
      RGD) by an incorporation of the Arg-Gly-Asp motif (RGD) containing peptide in the
      HI loop of the viral fiber knob domain, which enables the virus to contact target
      cells through alpha V integrins which are known to be ubiquitously expressed on
      the surface of mammalian cells. Ad-RGD showed a remarkable improvement (13-18
      fold) in the delivery of Escherichia coli LacZ gene in MG5 cells and a moderate
      increase in PCMG cells under the treatment with granulocyte-macrophage colony
      stimulating factor. These results suggest that Ad-RGD may be a potent tool for
      the delivery of genes to microglia activated by optimum stimulation, and thus
      analyzing the function of microglia with utilization of MG5 and PCMG cells.

PMID- 11988349
TI  - Noradrenergic receptors and in vitro respiratory rhythm: possible interspecies
      differences between mouse and rat neonates.
AB  - Similar in vitro experiments were performed on brainstem-spinal cord preparations
      from mouse and rat neonates to compare the noradrenergic regulations of the
      respiratory network. In preparations retaining the pons, rhythmic phrenic bursts
      occurred in rats but not in mice. Transection of the pons, electrolytic lesions
      and noradrenaline applications showed that the pontine noradrenergic A5 group
      inhibited the respiratory rhythm generator in both species but the inhibition was
      especially potent in mice. After pons elimination, noradrenaline applications to
      the medulla decreased the respiratory frequency in rats but increased it in mice.
      Noradrenergic agent applications revealed that the frequency changes implicated
      medullary alpha 1 and alpha 2 noradrenergic receptors in mice and rats,
      respectively. Thus, interspecies differences seem to exist in the noradrenergic
      regulations of the rat and mouse medullary respiratory networks.

PMID- 11988350
TI  - Metabotropic glutamate mGlu5 receptor-mediated modulation of the ventral
      striopallidal GABA pathway in rats. Interactions with adenosine A(2A) and
      dopamine D(2) receptors.
AB  - Interactions between subtypes of dopamine, glutamate and adenosine receptors seem
      to play an important integrative role in the function of striatal gamma
      aminobutyric acid (GABA)ergic efferent neurons. Recent behavioral and biochemical
      studies suggest the existence of specific interactions between adenosine A2A
      receptors (A(2A)R), dopamine D2 receptors (D2R) and the group I metabotropic
      mGlu5 receptors (mGlu5R) in the dorsal striatum. The dual-probe approach in vivo
      microdialysis technique in freely moving rats was used to study the role of
      mGlu5R/A2AR/D2R interactions in the modulation of the ventral striopallidal GABA
      pathway. Perfusion of a selective mGlu5R agonist (CHPG) in the nucleus accumbens
      facilitated GABA release in the ipsilateral ventral pallidum. This effect was
      strongly potentiated by co-perfusion with the A2AR agonist CGS 21680. Co
      perfusion with the D2R agonist quinpirole counteracted the increase in pallidal
      GABA levels induced by CGS 21680 and by CGS 21680 plus CHPG. These results
      demonstrate that mGlu5R/A2AR/D2R interactions play an important modulatory role
      in the function of the ventral striopallidal GABA pathway, which might have
      implications for the treatment of schizophrenia and drug addiction.

PMID- 11988351
TI  - Interactions between evening and nocturnal cortisol secretion and sleep
      parameters in patients with severe chronic primary insomnia.
AB  - Recent research provides evidence for an interaction between sleep and the
      activation of the hypothalamic-pituitary-adrenal (HPA)-axis, but detailed studies
      in patients are still missing. We investigated hourly evening and nocturnal
      plasma cortisol secretion and sleep in seven male patients with severe chronic
      primary insomnia and age- and gender-matched controls. Evening and nocturnal
      cortisol levels were significantly increased in patients. Evening cortisol
      correlated with the number of nocturnal awakenings in patients and controls.
      Additionally, patients showed significant correlations between sleep parameters
      and the first 4 h of nocturnal cortisol secretion. These results are indicative
      of changes in the HPA system in insomnia and may reflect a pathophysiological
      mechanism of chronic insomnia resulting in a vicious cycle of both disturbed HPA
      functions and chronic insomnia according to the arousal hypothesis of insomnia.

PMID- 11988352
TI  - Ion channels activated by cold and menthol in cultured rat dorsal root ganglion
      neurones.
AB  - A cold- and menthol-activated ionic current has been described in sensory
      neurones, which probably has a role in temperature sensing. Here we describe the
      ion channels underlying this current. Cooling activated non-selective cation
      channels (conductance, about 22 pS; reversal potential, -4.2 mV) in outside-out
      patches from cold-sensitive rat dorsal root ganglion neurones, and their activity
      was strongly increased by menthol. The activation threshold was 17.9 degrees C,
      shifting to 24.3 degrees C in 100 microM (-)-menthol, about 10 degrees C colder
      than observed in intact neurones. Channels in excised patches did not adapt to
      sustained cooling, unlike the current in intact neurones. We conclude that the
      ion channels underlying the cold- and menthol-induced current are directly
      activated by these stimuli, although other modulatory factors appear to be
      important in determining threshold and adaptation.

PMID- 11988353
TI  - Hot spot pollutants: pharmaceuticals in the environment.

PMID- 11988354
TI  - Occurrence, fate, and removal of pharmaceutical residues in the aquatic
      environment: a review of recent research data.
AB  - The occurrence and fate of pharmaceutically active compounds (PhACs) in the
      aquatic environment has been recognized as one of the emerging issues in
      environmental chemistry. In some investigations carried out in Austria, Brazil,
      Canada, Croatia, England, Germany, Greece, Italy, Spain, Switzerland, The
      Netherlands, and the U.S., more than 80 compounds, pharmaceuticals and several
      drug metabolites, have been detected in the aquatic environment. Several PhACs
      from various prescription classes have been found at concentrations up to the
      microg/l-level in sewage influent and effluent samples and also in several
      surface waters located downstream from municipal sewage treatment plants (STPs).
      The studies show that some PhACs originating from human therapy are not
      eliminated completely in the municipal STPs and are, thus, discharged as
      contaminants into the receiving waters. Under recharge conditions, polar PhACs
      such as clofibric acid, carbamazepine, primidone or iodinated contrast agents can
      leach through the subsoil and have also been detected in several groundwater
      samples in Germany. Positive findings of PhACs have, however, also been reported
      in groundwater contaminated by landfill leachates or manufacturing residues. To
      date, only in a few cases PhACs have also been detected at trace-levels in
      drinking water samples.

PMID- 11988355
TI  - The sorption and transport of a sulphonamide antibiotic in soil systems.
AB  - Veterinary medicines are administered to animals to treat disease and protect
      their health. After administration, the substances can be metabolised and a
      mixture of the parent compound and metabolites may be excreted in the urine and
      faeces. For animals on pasture, the excreta will be released directly to soil
      whereas for intensively reared animals, the main route of entry will be through
      slurry and manure spreading. Whilst the behaviour of other classes of substance
      (e.g. pesticides and nutrients) that are applied to soil is well understood,
      limited information is available on the transport and fate of veterinary
      medicines applied to soils. Laboratory and field studies were, therefore,
      performed to investigate the sorption behaviour of the sulfonamide antibiotic,
      sulfachloropyridazine, in soil and to assess the potential for
      sulfachloropyridazine to move from soil to surface waters and groundwaters.
      Sorption coefficients (K(D)) for the compound in soil and soil/slurry mixtures
      were low (ranging from 0.9 to 1.8 l kg(-1)) and indicated that the substance
      would be highly mobile. Field studies on a clay field supported these
      observations and demonstrated that, after application, the compound was rapidly
      transported to surface waters, concentrations of up to 590 microg l(-1) being
      observed in drainage waters. Leaching studies at a sandy site indicated that the
      substance had a low potential to leach to groundwaters, concentrations in the
      soil pore water being below or close to analytical detection limits. An
      assessment of currently available models for predicting concentrations of
      veterinary medicines entering surface waters indicated that for
      sulfachloropyridazine, the methods provide reasonable estimates, predicted
      concentrations being within a factor of two of the maximum measured
      concentrations. The approaches may not, however, be appropriate for use on highly
      hydrophobic substances or for predicting groundwater concentrations.

PMID- 11988356
TI  - Concentrations of the UV filter ethylhexyl methoxycinnamate in the aquatic
      compartment: a comparison of modelled concentrations for Swiss surface waters
      with empirical monitoring data.
AB  - UV filters in sunscreens and cosmetics protect the skin from damage through UV
      radiation. Many tonnes per year of UV filters are being used in Europe and will
      be present, at least seasonally, in detectable concentrations in surface waters
      similar to common pharmaceutically active substances. Predicted environmental
      concentrations (PECs) of ethylhexyl methoxycinnamate (EHMC; CAS 5466-77-3) were
      extrapolated for Switzerland, taking into consideration substance-specific
      environmental fate data and marketing estimates, by crude worst-case reckoning
      and by applying two environmental models (Mackay Level III; USES 3.0), both
      configured for Swiss hydrological and area data. By worst-case reckoning the
      summer PEC is 70.8-81.3 ng/l while for the remaining 8 months of the year the PEC
      is 13.1-15.1 ng/l. The Level III model results in concentrations of 2.4 ng/l
      during the summer and 0.44 ng/l during the rest of the year, while the USES 3.0
      model gives an average PEC for the whole year of 7.6 ng/l. Pooling summer
      monitoring data (90 single analyses) from the River Rhine below Basel in the year
      1997 (Water Protection Board of Basel) and from Lakes Zurich and Huttner in 1998
      (Poiger et al., in preparation) allowed a derivation of a probabilistic median
      concentration of 4.6 ng/l, a 95th-percentile concentration of 18.6 ng/l and a
      99th-percentile concentration of 33.5 ng/l. The 6-fold range from the median
      value to the maximum calls for caution in interpreting published monitoring
      concentrations. Comparison of modelled PECs with realistic median concentrations
      shows that crude reckoning overestimates actual concentrations by a factor of
      about 10, probably through insufficient consideration of (further) degradation of
      EHMC in sewage works, surface waters, sediments or river banks. Both computer
      models, in contrast, are within the same order of magnitude as the actual summer
      concentrations. Based on the available data, both these environmental fate and
      distribution models give realistic PECs.

PMID- 11988357
TI  - Exposure simulation for pharmaceuticals in European surface waters with GREAT-ER.
AB  - The Geo-referenced Regional Exposure Assessment Tool for European Rivers (GREAT
      ER) model was developed as an aquatic chemical exposure prediction tool for use
      within environmental risk assessment (ERA) schemes and river basin management.
      The GREAT-ER software calculates the distribution of predicted environmental
      concentrations (PECs) of consumer chemicals in surface waters, for individual
      river stretches, as well as representative average PECs for entire catchments.
      The system uses an ARC/INFO-ArcView (ESRI) based Geographical Information System
      (GIS) for data storage and visualization, combined with simple mathematical
      models for prediction of chemical fate. Use of GREAT-ER 1.03 to derive PECs is
      illustrated for Ethinyl Oestradiol, Paracetamol, Aspirin, Dextropropoxyphene,
      Clofibrate and Oxytetracycline in three river basins, i.e. Aire (UK), Lambro
      (Italy) and Rur (Germany). In contrast with household consumer chemicals the
      transformation of pharmaceuticals in the human body needs to be incorporated in
      the emission estimation. The "PECinitial" of these pharmaceuticals in surface
      waters ranges from >1 microg/l (Oxytetracycline and Paracetamol) down to <1 ng/l
      (Ethinyl Oestradiol). Risk characterization employing PECs or measured
      environmental concentrations (MECs) and predicted-no-effect-concentrations
      (PNECs) from available ecotoxicity data is also reported.

PMID- 11988358
TI  - Morphological sex reversal upon short-term exposure to endocrine modulators in
      juvenile fathead minnow (Pimephales promelas).
AB  - Indications of effects on fish endocrine system have been noted when exposed to
      effluents of sewage treatment plants and subsequently in the receiving surface
      waters. For screening purposes, the concentration of vitellogenin (VTG) in plasma
      is employed to detect potential exposure of fish, to (anti-)estrogenic
      substances. However, little is known about the variability of VTG determinations
      and morphological endpoints (secondary sexual characteristics) in fish under
      exposure conditions employing compounds with hormonal activity other than
      estrogens. An in vivo test system was established to study the effects of
      methyltestosterone (MT, a potential model androgen) and fadrozole (F, an
      aromatase inhibitor) as well as the combination of MT and F on juvenile, sexually
      undifferentiated fathead minnows (Pimephales promelas). Fish were exposed to
      those compounds continuously in the (nominal) microg/l range (MT, 10, 50 and 100
      microg/l; F, 25, 50, 100 microg/l; MT+F, 10 microg MT per l +50 microg F per l),
      for 14 days (MT+F) or 21 days (MT and F) using a flow-through system. The
      concentration of VTG and the expression of VTG mRNA was determined using whole
      body homogenates in an enzyme linked immunosorbant assay (ELISA) or reverse
      transcription-polymerase chain reaction (RT-PCR), respectively. Exposure to MT
      alone led to de novo mRNA expression as well as up to a four-fold increase of
      VTG. F had no effect on the VTG mRNA expression and VTG protein synthesis. The
      combination of MT and F had no effect on VTG concentrations, however, this
      produced a strong masculinisation of the juvenile fish, e.g. after 13 days of
      exposure 100% of the fish showed typical male sex characteristics, e.g. formation
      of nose tubercles and pigmentation of the dorsal fin. The above findings suggest
      that in fish MT may be aromatised to an estrogen. F, on the other hand, inhibits
      testosterone aromatisation. Consequently, the combination of MT and F strongly
      morphologically masculinised the juvenile fathead minnows. VTG detection at the
      mRNA and protein level is a sensitive parameter, however, it does not provide for
      any information regarding the baseline "estrogenicity" of a given parent
      compound.

PMID- 11988359
TI  - Determination of vitellogenin kinetics in male fathead minnows (Pimephales
      promelas).
AB  - A lack of knowledge persists concerning the combination of kinetics on protein
      and mRNA levels of the most commonly used biomarker for estrogenic influences
      vitellogenin (VTG). Consequently, male fathead minnows were exposed to 17alpha
      ethinylestradiol (EE(2)) for 35 days, followed by an equally long depuration
      period in a flow-through system. VTG mRNA levels reached a plateau after 3 days
      of exposure, which remained stable until 3 days after EE(2) removal. Control
      levels were re-attained within 7 days of the depuration phase. VTG protein
      accumulated in the plasma following a two-phased model. The first phase depicting
      an exponential increase lasted 15 days and was followed by a saturation phase
      approaching a plateau of approximately 47 mg VTG/ml plasma. Clearance kinetics
      could be described by a two-compartment open model, with half-lives of 2.17 and
      21.32 days for the alpha- and beta-phases, respectively. In addition, a high VTG
      protein synthesis rate seemed to adversely affect fitness and mortality of the
      fish.

PMID- 11988360
TI  - Reproductive and developmental effects of endocrine disrupters in invertebrates:
      in vitro and in vivo approaches.
AB  - In order to gain basic understanding in the ecotoxicity of endocrine disrupting
      chemicals or EDCs (including natural chemicals and some pharmaceuticals), many
      international research groups are currently testing these chemicals using aquatic
      invertebrates. This paper discusses relevant examples to address key questions:
      which aquatic invertebrates are likely to be vulnerable to mammalian and non
      mammalian EDCs; and which types of invertebrate chronic tests might be most
      sensitive and cost-effective to address potential environmental exposures? For a
      full review of invertebrate endocrine disrupter research see Endocrine Disruption
      in Invertebrates: Endocrinology, Testing and Assessment (1999). As an example,
      crustaceans are a particular focus of EDC research, reflecting their abundance in
      nature, commercial importance and their inclusion in the regulatory assessment
      schemes for active pharmaceutical ingredients (APIs). There is a diverse
      literature on the developmental and reproductive effects of mammalian EDCs in
      Crustacea, although there is growing evidence that such effects are probably not
      mediated via arthropod hormone systems. For example, recent studies in Europe
      using a marine copepod (Tisbe battagliai) life-cycle test have evaluated
      ecdysteroid agonists (e.g. 20-hydroxyecdysone), oestrogen agonists (e.g.
      diethylstilbestrol (DES), 17beta-oestradiol, oestrone and 17alpha
      ethynylestradiol) and the pharmaceutical anti-oestrogen (ZM189, 154). While 20
      hydroxyecdysone and DES were highly toxic, the other compounds tested show no
      significant toxicity to copepods. Furthermore, in vitro studies indicate that
      these environmental EDCs and several related APIs are not active against the
      ecdysteroid receptor. Therefore, other undefined modes of action appear to be
      responsible for crustacean toxicity in vivo and caution should be exercised
      before ascribing any apical effects to endogenous endocrine mechanisms, or before
      crustacean "EDC" data are extrapolated to other invertebrate taxa.

PMID- 11988361
TI  - Evaluation of immune functions of rainbow trout (Oncorhynchus mykiss)--how can
      environmental influences be detected?
AB  - In fish, the first line of defense against infectious microorganisms is based on
      a broad range of nonspecific humoral and cellular immune mechanisms ("innate
      immunity") which without prior specific activation can act in forming a more
      static barrier (Fish Shellfish Immunol. 10 (2000) 243; Dev. Comp. Immunol. 25
      (2001) 827). This natural resistance is normally effective enough to protect fish
      from infectious diseases until specific immune responses are being induced (Fig.
      1; Dev. Comp. Immunol. 25 (2001) 841). Healthy fish exhibit both nonspecific and
      specific immune responses depending directly on environmental temperature.
      Pollution of the natural aquatic environment with industrial or agricultural
      sewage is an important immunosuppressing factor resulting in higher
      susceptibility to infectious diseases. To date, the possible immunotoxicity of a
      substance is evaluated using quantification of humoral factors like lysozyme,
      complement, C-reactive protein or total immunoglobulins but less often using
      functional assays. Furthermore, most of the functional assays (phagocytosis,
      respiratory burst, proliferative response) are based on the measurement of the
      response of resting but not of specific activated immune cells. However, the
      physiological responses of the immune system to an infection are based on a
      complex, stepwise activation and proliferation, especially of the specific immune
      functions after first contact to the microorganisms. In this report we describe
      in vitro methods for the evaluation of cellular immune functions of different
      leukocyte populations after specific in vivo triggering of the immune system.
      Parameters to be evaluated are activation and proliferation of leukocyte
      populations, phagocytosis and respiratory burst, secretion of antigen-specific
      antibodies and specific cell-mediated cytotoxicity. Furthermore, challenge models
      with bacterial (Aeromonas salmonicida) and viral pathogens (Viral Haemorrhagic
      Septicemia Virus, VHSV) are presented.

PMID- 11988362
TI  - Environmental risk assessment of pharmaceutical drug substances--conceptual
      considerations.
AB  - Drugs, i.e. active ingredients of human medicinal products, may be introduced
      into the environment after use in patients by sewage effluent pathways and
      consequently are detected at low concentrations in sewage effluents and in
      surface waters. Legal requirements in a number of geographical regions (Europe,
      US, and intended in Canada) demand environmental risk assessments (ERA) for new
      drug substances. Existing regulatory concepts of ERA are based initially on a set
      of short-term ecotoxicological studies in three to four different species,
      environmental behavior and the application of assessment factors to correct for
      the ERA inherent uncertainty. Based on theoretical considerations and the
      experience with a very limited, but well investigated, number of examples while
      considering that drugs are highly biologically active compounds, the
      appropriateness of this risk assessment procedure for all drug substances might
      be questioned. Indeed, e.g. long-term effects may occur at much lower
      concentrations and follow different toxicodynamic mechanism than extrapolated
      from short-term studies., In such cases, the application of assessment factors
      for deriving chronic no-observed effect concentration (NOECs) appears to be
      problematic. Although long-term tests with a variety of organisms would provide a
      complete database for the evaluation of the environmental risks, this is
      unachievable for all drugs due to time, money and animal welfare constraints. In
      order to avoid unnecessary testing, a concept is presented, which makes use of
      pharmacological and toxicological, as well as pharmaco- and toxicokinetic
      information derived from mammals during drug substance development. Useful data
      for adoption in a case-by-case testing strategy can be obtained by evaluating (a)
      the pharmacological activity, which indicates specific targets in mammalian
      species and may allow for an analysis, whether a similar target is available in
      aquatic species; (b) the mammalian toxicity, which may indicate, which targets
      are most susceptible to adverse effects; (c) the difference between acute and
      chronic effects in mammals, since the magnitude of this difference may indicate,
      whether long-term effects are expected at significantly lower levels than acute
      effects; (d) the (pharmacologically and toxicologically) effective plasma levels
      in mammalian test organisms, which may be compared with the relevant exposure
      scenario for the environment. Additionally, activity classes of compounds may be
      established based on experience with specific substances, in order to develop an
      appropriate test strategy. The above preliminary considerations should support
      decisions on the selection of candidate substances for chronic effects studies
      and for the appropriate selection of test species and endpoints to monitor.
      Generally, ecologically relevant endpoints such as impairment of growth,
      development and reproduction should be used to assess the ecotoxicologic effects.

PMID- 11988363
TI  - Pharmacodynamic activity of drugs and ecotoxicology--can the two be connected?
AB  - Therapeutic agents, active substances as well as metabolites, have been detected
      in the environment, notably in the aquatic compartment. Such contamination may
      induce adverse environmental effects, and the question is, whether respective
      hazards could be deduced from their pharmacodynamic properties and activities,
      and whether there could indeed be relevant risks at the (very low) environmental
      concentrations observed. While it would seem that, in many cases, the
      concentrations of drugs needed to elicit pharmacodynamic responses will exceed
      the environmental concentrations by factors in the range of 10(4)-10(6), and
      while, furthermore, pharmacodynamically-mediated influences by drug residues on
      eco-organisms are possible only if the pharmacodynamic target (enzyme, receptor)
      is expressed and functionally active in some way in the respective eco-organism,
      such considerations should not, however, deflect from the fact that the
      specificities of drug substances are defined in terms of the human target
      structures, and that other organisms may exhibit different specificity profiles.
      Examples of such species specificities are discussed in this paper and lead to
      the conclusion that, on the one hand, pharmacodynamic effects, classified as
      secondary and considered irrelevant for the therapeutic activity in humans, might
      potentially play a major role in other (non-mammalian) eco-organisms, and that,
      on the other hand, the--"anthropocentrically" defined--primary pharmacodynamic
      activities of drugs could induce effects in (non-mammalian) eco-organisms totally
      different from the therapeutic effects. It is further argued that even slight,
      non-significant influences on single components within regulatory cascades, like
      cellular division or signal transduction, that would not result in any acutely
      discernible effect, might ultimately, through sequential propagation or through
      interaction with additional, unrelated factors, affect a whole population by its
      negative consequences on fitness: disturbances in hormonal homeostasis
      ("endocrine disruption"), in immunological status, in signal transduction or gene
      activation may serve as examples. From these considerations it is concluded that
      a more "mechanism-based" approach to the experimental investigation of potential
      environmental hazards through the contamination of, especially, the aquatic
      compartment by drug residues should therefore yield more meaningful results and
      insights than the indiscriminate use of a standard battery of ecotoxicology
      assays.

PMID- 11988364
TI  - Environmental risk assessment of veterinary medicinal products in the EU--a
      regulatory perspective.
AB  - The pharmacological nature of veterinary medicinal products, frequent application
      rates and use on a large scale for livestock production sensitizes regulation
      authorities for environmental concern. Consequently, in the European Union legal
      requirements plus guidance for an Environmental Risk Assessment of veterinary
      pharmaceuticals have been established. Applicants of new veterinary medicinal
      products have to provide an ecotoxicity report according to a guidance document
      which rests upon a logical, tiered approach with a cut-off trigger between a
      basic characterisation of the veterinary medicinal product and an in-depth
      assessment of its fate and ecotoxic effects. The outcome of this assessment is
      the establishment of the environmental risk that may arise from the use of the
      VMP under question. Contamination of the environment can be reduced by
      appropriate risk mitigation measures, e.g. limiting the application rate, the
      amount of contaminated manure being spread on agricultural lands or the access of
      treated pasture animals to surface waters.

PMID- 11988365
TI  - European medicines and feed additives regulation are not in compliance with
      environmental legislation and policy.
AB  - Environmental legislations for water and soil aim at the protection of quality of
      these compartments. This legislation has major consequences for product
      registration, amongst others the setting of environmental quality standards. A
      thorough risk assessment at registration of all products is crucial for the
      proper operationalisation of the environmental policy. A regulatory problem
      arises when the registration procedure is harmonised at a European level by the
      communautarian authority, while the authorities at the national level are
      responsible for maintaining the desired environmental quality. This problem can
      be tackled in two ways: firstly, the environmental risk assessment (ERA) should
      be based on common principles based on EU regulations and policy that steer the
      national authorities; secondly, the ERA should be developed under the supervision
      of competent authorities. Both options are not reflected in the forging of the
      ERA for medicines and feed additives. The formalisation of the contents and the
      procedure is not transparent nor open to input by scientists and other interested
      parties; the formalisation has no legal status, and European legislation cannot
      provide common protection goals in a global setting. The VICH Phase I and the
      EMEA Phase II guidance do not contain all communautarian environmental quality
      criteria, nor clear acceptability standards, nor harmonised methodology.
      Assessments are not made for all products, and the decision-making principles and
      practical procedures are not operational. It is therefore unlikely that any
      result of an ERA can be taken into consideration at registration, which
      undermines the legitimacy of the process. Both applicants and assessors are
      uncertain how to perform the risk assessment. The current developments may
      ultimately not only compromise product availability but also fail to protect the
      environment.

PMID- 11988366
TI  - Environmental risk assessment for new human pharmaceuticals in the European Union
      according to the draft guideline/discussion paper of January 2001.
AB  - Since 1993, an environmental risk assessment (ERA) for a new drug application has
      been stipulated by EU Directive 93/39/EEC amending Directive 65/65/EEC. In early
      2001, after several unpublished draft versions for an ERA guideline, a draft
      guideline/discussion paper for an ERA for non-GMO-containing drugs was published
      by the European Medicines Evaluation Agency (EMEA). The draft guideline describes
      a step-wise, tiered procedure for the ERA. The first tier consists of deriving a
      crude predicted environmental concentration (PEC) in the aquatic compartment for
      the active pharmaceutical ingredient (API) or its major metabolites, based on
      predicted amounts used and specific removal rates in sewage treatment or surface
      waters. If this crude PEC is <0.01 microg/l and no environmental concerns are
      apparent, no further assessment is deemed necessary. Else, in the second tier, a
      crude predicted no-effect level (PNEC) for the aquatic compartment is to be
      extrapolated by dividing the lowest 50%-effect concentration from acute
      ecotoxicity tests with algae, daphnia or fish (EC(50), LC(50)) by an assessment
      factor (usually 1000). If the ratio PEC/PNEC is <1, no further assessment is
      deemed necessary. Lastly, in the third tier, further considerations on a case-by
      case basis are needed. This may encompass refining the environmental fate
      information and thereby the PEC, considering further environmental compartments
      and their respective PECs (up to and including field studies), but also refining
      the PNEC. While the ERA addresses mainly the API, excipients of the formulated
      drug should be considered as well. In the case of medicinal products, the benefit
      for patients has relative precedence over environmental risks, meaning that even
      in the case of an unacceptable residual risk for new drugs after third-tier
      considerations, prohibition of a new API is not taken into consideration.
      Instead, possible mitigating or precautionary safety measures may consist of
      specific product labelling (i.e. package leaflets for the patients regarding
      returning and proper disposal of unused medicines), restricted use through in
      hospital or in-surgery administration under supervision only, or the
      recommendation of environmental analytical monitoring up to ecological field
      studies.

PMID- 11988367
TI  - Extent, pattern and factors associated with late embryonic loss in dairy cows.
AB  - Intensive genetic selection for increased milk production, coupled with increased
      dry matter intakes has led to significant improvements in cow milk yield,
      however, this increase in milk output has been accompanied by a decline in cow
      fertility. It has been suggested that there is a higher increment of late
      embryonic loss in high-yielding than in moderate yielding cows or in heifers. The
      objectives of this study were to establish the extent and pattern of embryonic
      loss, from days 28 to 84 of gestation, and to examine possible relationships
      between cow milk yield, cow genetic merit, parity, calving to insemination
      interval and embryonic loss in dairy cows managed mainly under pasture-based milk
      production systems. Multiparous dairy cows (n=1046) located on 8 farms and
      nulliparous dairy heifers (n=162) located on five of these farms were used in
      this study. The extent and timing of embryonic loss was measured by ultrasound
      scanning of the cows and heifers at 14-day intervals between days 28 and 84 of
      gestation. Positive diagnosis of pregnancy was based on the presence of an embryo
      or foetus with a visible heartbeat and, at the later scans, visible movement,
      whose size was compatible with stage of gestation and also on the presence of
      clear amniotic fluid of the cows and heifers presented as presumed pregnant on
      day 28 after insemination, 67 and 81%, respectively had a viable embryo. The
      subsequent embryonic loss rate between days 28 and 84 of gestation was similar
      (P>0.05) for cows (7.2%) and heifers (6.1%) and the pattern of loss over this
      period was also similar (P>0.05) for cows and heifers. There was no significant
      association (P>0.05) between level of milk production or milk energy output
      measured to day 120 of lactation and embryonic loss rate. Similarly, there was no
      significant relationship (P>0.05) between % milk fat, % milk protein and % milk
      lactose and embryonic loss rate. The extent and pattern of embryonic loss were
      not related (P>0.05) to either cow or to cow sire genetic merit. There was no
      significant (P>0.05) relationship between the calving to first service interval
      and embryonic loss. The extent of embryonic loss was greater (P<0.05) in cows
      that lost body condition between days 28 and 56 of gestation compared with cows
      than either maintained or improved in body condition.

PMID- 11988368
TI  - Motility and fertility of bull sperm in whole milk extender containing
      antioxidants.
AB  - Bull sperm are exposed to aerobic conditions during processing before freezing,
      and they have little endogenous antioxidant to protect them against reactive
      oxygen species that may be present. Seventeen laboratory studies and two field
      trials were conducted with 174 semen collections from bulls in an artificial
      breeding cooperative. More than 250 combinations and concentrations of reduced
      glutathione (GSH), superoxide dismutase (SOD), ascorbic acid, hypotaurine (HPT),
      2,2,6,6-tetramethylpeperidine-1-oxyl (Tempo) and 4-hydroxy-2, 2, 6, 6
      tetramethylpeperidine (Tempol) were tested by adding these compounds to fresh
      semen, and to a whole milk (WM) glycerol extender. Semen packaged in straws in
      the WM extender was frozen with liquid nitrogen. The motility of frozen-thawed
      sperm during storage at 25 or 5 degrees C after freezing was compared with semen
      stored without freezing. Antioxidants generally were not beneficial, except the
      percentage of motile sperm was improved by 6-11% units (P<0.05) when sperm were
      stored unfrozen or after freezing when 0.5mM of GSH with or without SOD was
      added. In two field trials, non-return rates were 71.9, 69.5 and 70.9% (P>0.05)
      with WM containing 0.0, 0.5 and 1.0mM of GSH, respectively, and 74.0 and 73.9%
      with WM and WM plus 0.5mM of GSH and 100U/ml of SOD (P>0.05). WM contains an
      abundant supply of casein which is an antioxidant, and additional antioxidants
      were ineffective in improving motility of sperm immediately after freezing and
      thawing or in affecting fertility. However, sperm responses were different in egg
      yolk-Tris extender. Sperm in this egg yolk extender tolerated substantial
      concentrations of Tempo and Tempol compared with toxic effects in WM (P<0.05).
      Therefore, optimal combinations of antioxidants tested here may have more useful
      applications in organizations using an egg yolk-based semen extender.

PMID- 11988369
TI  - Bull selection and use in northern Australia. 1. Physical traits.
AB  - A systematic breeding soundness examination, including assessment of serving
      capacity was conducted on 5/8 Brahman, Brahman and Belmont Red bulls, most aged 2
      4 years, at 12 different cattle properties across northern Australia. A subset of
      bulls (n=235) were subsequently mated in various groups, as multiple-sires, to
      cows and heifers at bull:female ratios of 2.5-6%. The number of calves sired by
      individual bulls (calf output) was determined by DNA typing for paternity.
      Overall, the incidence of physical abnormalities that were judged likely to
      result in reduced reproductive performance was low (5.6-12% of bulls). Measures
      of key physical traits scrotal circumference, sheath depth (vertical distance
      from ventral abdominal wall to preputial orifice), and sheath score were
      moderately to highly repeatable. Except in Belmont Red bulls, liveweight was
      positively correlated with scrotal circumference (r=0.36-0.78; P<0.01), and both
      traits increased with age. In 2-year-old Brahman bulls only, percent normal
      spermatozoa was correlated with scrotal circumference (r=0.34; P<0.05). However,
      12 and 15% of Santa Gertrudis and Brahman bulls, respectively, with greater than
      or equal to the recommended threshold values for scrotal circumferences, had less
      than 50% morphologically normal spermatozoa. Size and conformation of the
      umbilicus was associated with conformation of the sheath, and influenced mating
      ability in 2-year-old Brahman and 3-year-old Santa Gertrudis bulls. In 2-year-old
      Brahman bulls umbilical cord thickness was positively related (r=0.36; P<0.05) to
      sheath depth, and negatively related (r=-0.65; P<0.05) to number of mounts and
      serves in a serving capacity test. In 3-year-old Santa Gertrudis bulls navel
      (external umbilical scar) score was negatively related to the number of serves
      (r=-0.53; P<0.01) in a serving capacity test. None of the physical traits
      measured were consistently included in the final regression model for calf output
      for each breed.

PMID- 11988370
TI  - Bull selection and use in northern Australia. Part 2. Semen traits.
AB  - Detailed semen evaluations were carried out on approximately 363 Santa Gertrudis,
      5/8 Brahman and Brahman bulls on 12 different properties across northern
      Australia, as part of systematic breeding soundness examinations. A subset of
      bulls (n=245) were subsequently mated in groups, to cows and heifers at
      bull:female ratios of 2.5-6.0%, with the paternity of resulting calves being
      determined by microsatellite DNA testing. Motility traits of semen and
      spermatozoa were moderately repeatable and correlated with each other, but were
      unrelated to calf output. The percentage of morphologically normal spermatozoa in
      ejaculates was moderately to highly repeatable (e.g. r=0.10-0.64). The most
      common morphological abnormalities seen were mid-piece abnormalities, in
      particular, distal mid-piece reflex associated with a cytoplasmic droplet. Semen
      quality, particularly percent normal spermatozoa, was consistently related to
      calf output. In general, bulls with <50% normal spermatozoa sired few calves
      while bulls with the highest calf outputs had >70% normal spermatozoa. The
      presence or absence of heparin binding proteins in semen did not influence calf
      output. Semen from 93% of tested bulls was positive for heparin binding proteins.
      These results confirm that examination of semen, in particular, evaluation of
      percent morphologically normal spermatozoa, should be included in the breeding
      soundness examination of bulls.

PMID- 11988371
TI  - Bull selection and use in northern Australia. 3. Serving capacity tests.
AB  - Serving capacity studies were conducted on Santa Gertrudis, 5/8 Brahman, Brahman
      and Belmont Red bulls at 10 sites. Modifications, such as providing prior sexual
      experience, using females in oestrus and comparing restrained with unrestrained
      females, were made to the standard Bos taurus serving capacity test in a series
      of experiments with Santa Gertrudis bulls. Providing sexual experience to virgin
      bulls prior to testing improved the number of serves and libido scores in a
      serving capacity test. In serving capacity tests that used restrained females,
      expressions of sexual behaviour of bulls were not improved by having females in
      oestrus compared with non-oestrus females. There were more sexual behaviours,
      particularly mounts, in serving capacity tests involving restrained rather than
      unrestrained females. Summary statistics were collated from over 1100 serving
      capacity tests, in the 2 months prior to mating, across the 10 sites. In serving
      capacity tests using restrained females, in bulls of the same age, there were
      more expressions of sexual behaviours (except interest) in Belmont Red than in
      Brahman or 5/8 Brahman bulls with Santa Gertrudis bulls intermediate. The
      percentage of bulls displaying serves tended to increase with age; 82, 83 and 86%
      of 2-, 3- and > or =4-year-old Belmont Red bulls, respectively, completed 1 or
      more serves. This compared with 50, 50 and 66% of 2-, 3- and > or =4-year-old
      Santa Gertrudis bulls and 31% of 2-year-old Brahman bulls. Between 2 and 9% of
      bulls did not display any sexual behaviour in serving capacity tests with
      restrained females. Across genotypes, there were few and inconsistent
      relationships between either mounts or serves and liveweight, condition score,
      scrotal circumference, testicular tone and sheath measurements. The exceptions
      were in 2-year-old Brahmans where mounts were negatively correlated (r=-0.61;
      P<0.05) with umbilicus thickness and in 3-year-old Santa Gertrudis bulls, where
      serves (r=-0.53; P<0.01) and mounts+serves (r=-0.49; P<0.01) were negatively
      correlated with navel score. Measures of sexual behaviour were unable to
      consistently predict calf output of bulls in multiple-sire mating groups in
      extensive pastoral conditions. The main value of the serving capacity test in
      these genotypes is to identify whether a bull is capable of natural service.

PMID- 11988372
TI  - Bull selection and use in northern Australia. 4. Calf output and predictors of
      fertility of bulls in multiple-sire herds.
AB  - On 10 northern Australian properties, the number of calves sired (calf output) by
      individual bulls in multiple-sire matings was measured by DNA typing for
      paternity. There were 235 bulls (92 Santa Gertrudis, 25 5/8 Brahman and 119
      Brahman) from 37 multiple-sire mating groups. Number of bulls in groups ranged
      from 2 to 25 and ages of bulls ranged from 2 to 5 years. Mating periods were for
      3-12 months and bull mating percentages were 2.5-6%. In all, there were 4251
      calves tested and the resolution of paternity ranged from 92.5 to 100% and
      averaged 97.7% across all sites. This included 9.9% of calves with no potential
      sires in any of the mating groups. Of the 235 bulls mated, 58% sired 10% or less
      calves in each of their respective mating groups with 6% not siring any calves.
      In contrast, 14% sired over 30% of the calves in each of the respective mating
      groups. When bulls were mated in groups of 8-24, the maximum percent of calves
      sired by individual bulls was 26+/-7% (mean+/-S.D.) with a range 11-36%. However,
      when bulls were mated in groups of 2-7, the maximum percent of calves sired by
      individual bulls was 59+/-19% with a range 24-94%. Calf output of bulls was
      moderately repeatable across years at four of five sites. Multiple regression
      models relating pre-mating measures of physical, seminal and behavioural traits
      to calf output were developed for the three breed groups. In all, only 138 of the
      235 bulls were included in the models (40 Santa Gertrudis, 24 5/8 Brahman and 74
      Brahman). Sheath and testicular traits, such as scrotal circumference and
      testicular tone, were generally not related to calf output, the exceptions being
      sheath depth in Brahman bulls which was negatively related (P<0.05) and scrotal
      circumference in 5/8 Brahmans which was positively related (P=0.08) to calf
      output. Dominance was only included in the 5/8 Brahman model but there was no
      significant relationship between dominance hierarchy and calf output. Semen
      motility was only related (P<0.05) to calf output in 5/8 Brahmans. However,
      measures of semen quality based on spermatozoa morphology were important
      contributors to calf output in the Santa Gertrudis and Brahman models where
      percent normal spermatozoa was positively related (P<0.01) to calf output. In
      Santa Gertrudis and Brahman bulls, measures of sexual behaviour in the serving
      capacity test were related to calf output. In Santa Gertrudis, these were for the
      number of displays of sexual interest (P<0.05), and mounts (P<0.01), but not
      number of serves, whilst in Brahman bulls, libido score was positively related to
      calf output (P<0.05). The models only explained 35-57% of the variation in calf
      output.

PMID- 11988373
TI  - Bull selection and use in northern Australia. 5. Social behaviour and management.
AB  - Calf output of bulls was derived using DNA typing for paternity following
      multiple-sire mating at two sites in northern Australia. At Swan's Lagoon Beef
      Cattle Research Station, 12, mixed-age, Brahman cross bulls were continuously
      mated with an average of 325 females in a 22km2 open-savannah paddock. Water was
      available in two troughs. Behaviour of the bulls and location of cows were
      monitored. At Kamilaroi Station, 2- to 2.5-year-old Brahman bulls were introduced
      to the study. Twenty-four bulls (HIGH%) were mated in an 84km2 paddock for 3.5
      months to 411 heifers in 1995/1995 and for 4.5 months to 350 heifers and 320
      first-lactation cows in 1995/1996. A second group of 10 bulls (LOW%) selected on
      reproductive soundness was mated concurrently in a neighbouring 60km2 paddock to
      411 heifers in 1995/1995 and to 350 heifers and 298 first-lactation cows in
      1995/1996. In each paddock in both years, 300-350 females were expected to cycle
      during mating. Both paddocks were flat and semi-forested and water was available
      only at troughs. At both sites, detailed physical and reproductive examinations
      of all bulls were conducted prior to and post-mating.Calf output of individual
      bulls was highly variable but repeatable (r=0.6-0.7) between years. Up to 90% of
      the 270-380 calves resulting from each mating were sired by between 6 and 8
      bulls. Reducing from 3.7 to 2.8% bulls:females at Swan's Lagoon did not delay
      conceptions. At Kamilaroi, reproductively sound bulls achieved an estimated 5-6
      conceptions per week over the peak mating period when sufficient cycling females
      were available. Differences in pregnancy rates between paddocks appeared due to
      differences in nutrition and it appeared that conceptions were not delayed with
      LOW% vs. HIGH% bulls. Variance between bulls in calf output was substantially
      lower when fewer bulls were used. Bull attrition occurred each year in the HIGH%
      paddock but not in the LOW% paddock. Calf output was unrelated to body condition
      of bulls. Seven of the 12 bulls in one 2-year period at Swan's Lagoon appeared to
      restrict their movement range to 250-750ha for 90-100% of the time. These ranges
      expanded when the bull:female ratio was reduced. Only one of the nine bulls
      remained within a 500ha home range for at least 85% of the time during peak
      mating in 1998 at 2.8% bulls:females. In previous years with 3.7% bulls:females,
      up to eight of the 12 bulls had remained within a 500ha home range for 85% of the
      time. Bull behaviour related to high calf output included restricted movement
      range, grazing with females at a majority of observations, stable social
      behaviour, and social dominance. These observations demonstrate that multiple
      sire mating of reproductively sound Brahman and Brahman-derived bulls at 2.5% of
      cycling females will not jeopardise herd fertility under extensive management in
      northern Australia.

PMID- 11988374
TI  - Survival of oocytes recovered from vitrified sheep ovarian tissues.
AB  - The objective of this work was to develop an effective vitrification technique
      for cryopreserving oocytes in sheep ovarian tissues. Ovaries were surgically
      recovered from 15 pubertal ewes and the ovarian cortex was cut into sections.
      Ovarian tissues were placed in equilibration medium consisting of 4% (v/v)
      ethylene glycol (EG) and 20% (v/v) FBS in TCM-199 on ice for 30 min and
      transferred to vitrification solution (35% EG, 5% polyvinylpyrrolidone, 0.4M
      trehalose and 20% FBS in TCM-199) for 5 min. Ovarian tissues were vitrified by
      dropping the tissue on the surface of a steel cube cooled by liquid nitrogen.
      Cumulus-enclosed oocyte complexes (COC) were also collected and vitrified
      following the procedure used for ovarian tissues. After 2-3 weeks of storage in
      liquid nitrogen, ovarian tissues and COC were thawed at 37 degrees C in 0.3M
      trehalose and COC in ovarian tissues were mechanically and enzymatically
      isolated. Vitrified COC and freshly collected COC were washed twice in maturation
      medium (TCM-199 supplemented with 0.255 mM pyruvate and 10% heat-treated estrus
      cow serum) and cultured in 50 microl drops of maturation medium under paraffin
      oil for 23-25h at 39 degrees C in a humidified atmosphere of 5% CO(2) in air.
      After culture, cumulus cells were removed by hyaluronidase treatment and
      vortexing and oocytes were fixed and stained. No significant differences were
      observed between vitrified oocytes, oocytes recovered from vitrified ovarian
      tissues and non-vitrified control oocytes in the percentage of oocytes with
      acceptable staining per total number of oocytes fixed or with visible chromatin
      per total number of oocytes with acceptable staining. However, fewer (P<0.05)
      oocytes obtained from vitrified ovarian tissues (70%) reached metaphase II
      compared to vitrified oocytes (88%) and non-vitrified control oocytes (90%). In
      contrast, when oocytes with at least 3-5 layers of cumulus cells were considered
      from each of the three groups, no differences (P>0.05) were observed due to
      treatment in the percentages of oocytes developing to metaphase II. These results
      demonstrate that sheep oocytes can be successfully cryopreserved by vitrification
      of ovarian tissues and exhibit in vitro maturation rates similar to that of
      vitrified and non-vitrified oocytes.

PMID- 11988375
TI  - Reverse effect of indomethacin on the immunosuppressive activity of boar seminal
      immunosuppressive fraction.
AB  - The inhibitory activity of seminal immunosuppressive fraction (ISF) on mitogen
      stimulated lymphocyte proliferation and on production of antibody to a soluble
      antigen was modified by indomethacin or monoclonal antibody to ISF. The ability
      of indomethacin or monoclonal antibody to ISF to reverse the ISF-induced
      inhibition of mitogen-stimulated lymphocyte proliferation was estimated by
      measuring bromodeoxyuridine incorporation into replicated DNA. Splenocytes from
      mice treated with indomethacin or monoclonal antibody to ISF prior to the
      application of ISF were tested. The ability of indomethacin or monoclonal
      antibody to ISF to reverse ISF-induced suppression of antibody production was
      estimated by measuring antibody titers by ELISA in the blood sera from mice
      immunized with keyhole limpet hemocyanin (KLH). These animals were treated with
      indomethacin or monoclonal antibody to ISF prior to the application of ISF. The
      results showed that both indomethacin and monoclonal antibody to ISF reversed the
      inhibitory effect of ISF on mitogen-stimulated lymphocyte proliferation as well
      as on antibody production.Recently, we have identified ISF as a complex of the
      major seminal glycoproteins PSP I and PSP II. PSP II is the part that is
      responsible for immunosuppressive properties of the complex. To learn whether the
      ISF immunosuppressive effect is associated with its protein or saccharide part,
      we examined the deglycosylated PSP II for its antiproliferative effect on mitogen
      stimulated mouse lymphocytes. The results suggest that deglycosylation of PSP II
      did not affect its antiproliferative activity. This suggest that PSP II
      immunosuppressive properties are associated with the protein and not the
      saccharide part of the molecule.

PMID- 11988376
TI  - Determination of the ovulatory mechanism of the grasscutter (Thryonomys
      swinderianus).
AB  - The ovulatory mechanism of the grasscutter was determined in two phases. Phase
      one was the histological examination of ovaries of sexually mature grasscutters
      in various reproductive conditions (non-mated, mated, pregnant) for Corpora lutea
      (an indicator of ovulation). The second phase was an evaluation of the
      reproductive performance (female's acceptance to mate, ability to conceive and
      deliver) of sexually mature grasscutters in oestrus (open vagina, sealed vagina)
      and anoestrus (closed vagina). The ovaries for the histological studies were
      obtained from 25 grasscutters comprising nine females that had been paired with
      males for 1 week prior to the collection of their ovaries, nine that had not been
      exposed to males for a minimum of 6 months and carcases of seven pregnant
      grasscutters. Thirty sexually mature female and eight sexually mature male
      grasscutters were used for the reproductive study. The females were in three
      groups of ten in three different sexual states namely; open vagina (oestrus),
      sealed vagina (oestrus) and closed vagina (anoestrus). The animals were hand
      mated in pairs and separated when a definitive sign of mating was observed.
      Thereafter, the females were diagnosed for pregnancy and observed until
      parturition. The histological examinations showed an unequivocal absence of
      Corpora lutea in the ovaries of the grasscutters that had not been exposed to
      males, but their presence in the ovaries of the mated and pregnant grasscutters.
      In the reproductive study, 96.7% (29/30) were successfully mated, 96.6% (28/29)
      of those mated conceived and 89.3% (25/28) of those pregnant carried their
      pregnancies to term. None of these outcomes was affected by the sexual status.
      The histological and reproductive findings confirm the suggestion that the
      grasscutter is an induced ovulator. This information is important for the
      commercial exploitation of the animal for human food production.

PMID- 11988377
TI  - Heat-related mortality during a 1999 heat wave in Chicago.
AB  - BACKGROUND: During the summer of 1999, Chicago's second deadliest heat wave of
      the decade resulted in at least 80 deaths. The high mortality, exceeded only by a
      1995 heat wave, provided the opportunity to investigate the risks associated with
      heat-related deaths and to examine the effectiveness of targeted heat-relieving
      interventions. METHODS: We conducted a case-control study to determine risk
      factors for heat-related death. We collected demographic, health, and behavior
      information for 63 case patients and 77 neighborhood-and-age-matched control
      subjects and generated odds ratios (ORs) for each potential risk factor. RESULTS:
      Fifty-three percent of the case patients were aged <65 years, and psychiatric
      illness was almost twice as common in the younger than the older age group. In
      the multivariate analysis, the strongest risk factors for heat-related death were
      living alone (OR=8.1; 95% confidence interval [CI], 1.4-48.1) and not leaving
      home daily (OR=5.8; 95% CI, 1.5-22.0). The strongest protective factor was a
      working air conditioner (OR=0.2; 95% CI, 0.1-0.7). Over half (53%) of the 80
      decedents were seen or spoken to on the day of or day before their deaths.
      CONCLUSIONS: A working air conditioner is the strongest protective factor against
      heat-related death. The relatively younger age of case patients in 1999 may be
      due to post-1995 interventions that focused on the elderly of Chicago. However,
      social isolation and advanced age remain important risk factors. Individual
      social contacts and educational messages targeted toward at-risk populations
      during heat waves may decrease the number of deaths in these groups.

PMID- 11988378
TI  - Progression to established smoking: the influence of tobacco marketing.
AB  - BACKGROUND: Recent studies have shown that tobacco advertising leads to the onset
      of smoking among adolescents. However, much more still remains to be learned
      about the impact of tobacco advertising in the later transitions, mainly from
      experimentation to established smoking. In this study, we focused on the
      influence of tobacco advertising and promotions on the transition from
      experimentation to established smoking. METHODS: Data were derived from a
      longitudinal survey of adolescents in California. Adolescents who were classified
      as experimenters at baseline were included in the analyses (N=965). Receptivity
      to tobacco advertising and promotions refers to the development of a positive
      affective response to the communication (e.g., having a favorite tobacco
      advertisement or being willing to use a promotional item). RESULTS: Approximately
      32% of adolescents who were experimenters at baseline in 1993, progressed to
      established smoking by follow-up in 1996. Progression was higher among Caucasian
      (37.3%) than Hispanic (21.9%) or African-American (17.6%) adolescents.
      Adolescents who perceived that most of their peers smoked, had poor relationships
      with family members, and were exposed to smoking friends and family members were
      more likely to progress to established smoking at follow-up in 1996. In addition,
      adolescents who were receptive to advertising and believed that they could quit
      anytime were more likely to progress to established smoking than those who did
      not think they could quit anytime. Adolescents who were willing to use a
      promotional item and who believed that they could quit anytime had the highest
      rate of progression to established smoking (52%). CONCLUSIONS: This study
      provides evidence that receptivity to tobacco advertising and promotions is an
      important factor in progressing from experimentation to established smoking among
      adolescents. Because perceived ability to quit made adolescents more likely to
      progress, counter-tobacco marketing campaigns should incorporate messages about
      addiction and difficulties associated with quitting.

PMID- 11988379
TI  - Effects of gender on relapse prevention in smokers treated with bupropion SR.
AB  - BACKGROUND: Recent data suggest that women smokers respond differently than men
      to cessation pharmacotherapies, particularly nicotine replacement therapy (NRT).
      Lower abstinence and higher relapse rates are often reported for women treated
      with NRT. Gender effects for those treated with non-nicotinic, bupropion
      hydrochloride sustained release for relapse prevention have not been studied.
      METHODS: Data from a multicenter relapse-prevention (RP) trial of bupropion
      (November 1995-June 1998) were analyzed for gender differences. Men and women
      smokers (N=784) were treated with open-label bupropion for 7 weeks. Those
      abstinent at Week 7 (n=432) were enrolled in the double-blind relapse-prevention
      phase and randomized to placebo or continued bupropion for 45 additional weeks.
      RESULTS: Differences in point-prevalence abstinence rates between men (61.8%) and
      women (55.6%) in open-label bupropion (Week 7) were not significant. In the RP
      phase Week 52, continuous abstinence rates for men and women were 37.8% and 36.4%
      (bupropion) and 36.6% and 29.9% (placebo), respectively; point-prevalence
      abstinence rates for men and women were 54.1% and 55.9% (bupropion) and 42.9% and
      41.3% (placebo), respectively. Abstinence rates and time to relapse were superior
      for both men and women who received longer treatment. Gender differences within
      treatment groups were not significant. Median time to relapse was equal for men
      and women within each treatment group: Week 32 for bupropion and Week 20 for
      placebo. CONCLUSIONS: Our data suggest that bupropion is a promising
      pharmacotherapy for preventing relapse, particularly for women.

PMID- 11988380
TI  - Patterns of fruit, vegetable, and milk consumption among smoking and nonsmoking
      female teens.
AB  - BACKGROUND: The increase in teenage smoking, and the fact that concern about body
      weight is given as a reason for smoking initiation by girls, suggest that food
      intake may be compromised in female teens who smoke. Daily consumption of a
      variety of foods is important due to the health-protective constituents they
      contain. Few studies have documented how smoking and the consumption of fruits,
      vegetables, and milk may be associated in female teens. METHODS: This study
      examined the relationship of smoking and the consumption of fruit, fruit juice,
      vegetables, and milk in ninth- to twelfth-grade Caucasian (n=2797), African
      American (n=2196), and Hispanic (n=2052) female teens. Data from the Youth
      Behavior Risk Survey (1999) were analyzed with SUDAAN software, using logistic
      regression models. RESULTS: Smoking was significantly associated with decreased
      odds of consuming milk at 0.74 (95% confidence interval [CI], 0.55-0.98); fruit,
      0.70 (95% CI, 0.54-0.92); fruit juice, 0.74 (95% CI, 0.56-0.98); and vegetables,
      0.75 (95% CI, 0.63-0.89) among Caucasian female teens, and with decreased odds of
      consuming fruit juice among Hispanic female teens at 0.59 (95% CI, 0.40-0.89).
      For each significant food variable, a dose-response relationship was detected
      with significantly more females consuming each food at lower smoking levels and
      significantly fewer doing so at the highest level (p<0.05). By contrast, African
      American female teen smokers tended to consume higher levels of the specified
      food/beverages than nonsmokers, but this relationship was not statistically
      significant. IMPLICATIONS: This study establishes a smoking/food intake
      interaction for the specific foods tested, in an adolescent female population.
      Compromising the intake of healthy foods and their protective nutrients leaves
      young women more vulnerable to the serious health consequences of smoking. These
      results underscore the need for young women to be educated on the importance of
      eating maximum servings of fruits and vegetables and dairy products, such as
      milk, particularly if they smoke or are at risk for smoking initiation. The study
      also underscores the need to culturally tailor programs according to differences
      in smoking initiation and eating/dieting behaviors.

PMID- 11988381
TI  - Effects of a mammography decision-making intervention at 12 and 24 months.
AB  - BACKGROUND: Most women are not getting regular mammograms, and there is confusion
      about several mammography-related issues, including the age at which women should
      begin screening. Numerous groups have called for informed decision making about
      mammography, but few programs have resulted. Our research is intended to fill
      this gap. METHODS: We conducted a randomized controlled trial, which ran from
      1997 to 2000. Women aged 40 to 44 and 50 to 54, who were enrolled in Blue Cross
      Blue Shield of North Carolina, were randomly assigned to one of three groups:
      usual care (UC), tailored print (TP) materials, or TP plus tailored telephone
      counseling (TP+TC). We assessed the impact of tailored interventions on knowledge
      about breast cancer and mammography, accuracy of breast cancer risk perceptions,
      and use of mammography at two time points after intervention-12 and 24 months.
      RESULTS: At 12 and 24 months, women who received TP+TC had significantly greater
      knowledge and more accurate breast cancer risk perceptions. Compared to UC, they
      were 40% more likely to have had mammograms (odds ratio=0.9-2.1). The effect was
      primarily for women in their 50s. TP had significant effects for knowledge and
      accuracy, but women who received TP were less likely to have had mammography.
      CONCLUSIONS: Decision-making interventions, comprised of two tailored print
      interventions (booklet and newsletter), delivered a year apart, with or without
      two tailored telephone calls, significantly increased knowledge and accuracy of
      perceived breast cancer risk at 12 and 24 months post-intervention. The effect on
      mammography use was significant in bivariate relationships but had a much more
      modest impact in multivariate analyses.

PMID- 11988382
TI  - Absence of risk factor change in young adults after family heart attack or
      stroke: the CARDIA Study.
AB  - BACKGROUND: Health behavior theories suggest that occurrence of heart attack or
      stroke in an immediate family member should increase one's perceived
      susceptibility to these conditions, which might lead to improved risk factor
      behavior and control. METHODS: Changes in measures of smoking, physical activity,
      lipids/lipoproteins, body weight, and blood pressure were investigated over two
      consecutive 5-year follow-up periods among 3950 participants (aged 18 to 30
      years) in the Coronary Artery Risk Development in Young Adults (CARDIA) study,
      who either did or did not have an immediate family member experience a heart
      attack or stroke. Recruitment and examinations for Years 0, 5, and 10 took place
      in 1985-1986, 1990-1991, and 1995-1996, respectively. RESULTS: After adjustment
      for baseline demographics and risk factors, young adults who experienced a change
      in family history of heart attack or stroke over a 5-year period were no more
      likely than those who did not to quit smoking, or to experience more positive
      changes in weight, physical activity, LDL cholesterol, HDL cholesterol,
      triglycerides, or systolic or diastolic blood pressure. These findings persisted
      among the few study participants with one or more established risk factors at
      baseline. CONCLUSIONS: The occurrence of a heart attack or stroke in an immediate
      family member does not appear to lead to self-initiated, sustained change in
      modifiable risk factors in young adults. Since family history of heart attack and
      stroke is associated with known risk factors and is an independent risk factor
      for incident development of these conditions, interventions should be developed
      and tested to motivate sustained risk-factor control following occurrence of a
      severe vascular event in a family member.

PMID- 11988383
TI  - Evaluating primary care behavioral counseling interventions: an evidence-based
      approach.
AB  - Risky behaviors are a leading cause of preventable morbidity and mortality, yet
      behavioral counseling interventions to address them are underutilized in
      healthcare settings. Research on such interventions has grown steadily, but the
      systematic review of this research is complicated by wide variations in the
      organization, content, and delivery of behavioral interventions and the lack of a
      consistent language and framework to describe these differences. The Counseling
      and Behavioral Interventions Work Group of the United States Preventive Services
      Task Force (USPSTF) was convened to address adapting existing USPSTF methods to
      issues and challenges raised by behavioral counseling intervention topical
      reviews. The systematic review of behavioral counseling interventions seeks to
      establish whether such interventions addressing individual behaviors improve
      health outcomes. Few studies directly address this question, so evidence
      addressing whether changing individual behavior improves health outcomes and
      whether behavioral counseling interventions in clinical settings help people
      change those behaviors must be linked. To illustrate this process, we present two
      separate analytic frameworks derived from screening topic tools that we developed
      to guide USPSTF behavioral topic reviews. No simple empirically validated model
      captures the broad range of intervention components across risk behaviors, but
      the Five A's construct-assess, advise, agree, assist, and arrange-adapted from
      tobacco cessation interventions in clinical care provides a workable framework to
      report behavioral counseling intervention review findings. We illustrate the use
      of this framework with general findings from recent behavioral counseling
      intervention studies. Readers are referred to the USPSTF
      (www.ahrq.gov/clinic/prevenix.htm or 1-800-358-9295) for systematic evidence
      reviews and USPSTF recommendations based on these reviews for specific behaviors.

PMID- 11988384
TI  - The rise and fall of occupational medicine in the United States.
AB  - Thirty years ago, occupational medicine was one of the smallest of all the
      medical specialties, ignored by most physicians and medical schools. Occupational
      physicians were more likely to have entered the field through career transition
      than by residency training. In 1970, governmental agencies sought to transform
      occupational medicine into a major clinical specialty. Influential groups
      projected a need for large numbers of physicians in the field. Residency training
      was expanded, as were other teaching programs. However, industry and its workers'
      compensation insurance partners were not widely included in these plans. For that
      reason, among others, many physicians entering the field met with disappointment.
      About half the corporate positions for occupational physicians have disappeared
      in the last decade. Private practice opportunities turned out to be much more
      limited than planners had anticipated. Attempts to bring occupational medicine
      into the curriculum of the medical schools failed. Many of the residency programs
      that had been created are now closing. The proposal that occupational medicine
      create a joint specialty with environmental medicine is not widely accepted by
      the rest of medicine. Because so few physicians obtain board certification, it
      appears that the specialty of occupational medicine is returning to its former
      obscurity.

PMID- 11988385
TI  - History of the American Board of Preventive Medicine.

PMID- 11988386
TI  - One minute for prevention: the power of leveraging to fulfill the promise of
      health behavior counseling.

PMID- 11988387
TI  - A cure for preventive medicine.

PMID- 11988388
TI  - The continuing rise of occupational medicine.

PMID- 11988389
TI  - Heat-related illness: current status of prevention efforts.

PMID- 11988393
TI  - Fluorescence detection of plant extracts that affect neuronal voltage-gated Ca2+
      channels.
AB  - Structurally novel compounds able to block voltage-gated Ca2+ channels (VGCCs)
      are currently being sought for the development of new drugs directed at
      neurological disorders. Fluorescence techniques have recently been developed to
      facilitate the analysis of VGCC blockers in a multi-well format. By utilising the
      small cell lung carcinoma cell line, NCI-H146, we were able to detect changes in
      intracellular Ca2+ concentration ([Ca2+](i)) using a fluorescence microplate
      reader. NCI-H146 cells have characteristics resembling those of neuronal cells
      and express multiple VGCC subtypes, including those of the L-, N- and P-type. We
      found that K+-depolarisation of fluo-3 loaded NCI-H146 cells causes a rapid and
      transient increase in fluorescence, which was readily detected in a 96-well
      plate. Extracts of Australian plants, including those used traditionally as
      headache or pain treatments, were tested in this study to identify those
      affecting Ca2+ influx following membrane depolarisation of NCI-H146 cells. We
      found that E. bignoniiflora, A. symphyocarpa and E. vespertilio caused dose
      dependent inhibition of K+-depolarised Ca2+ influx, with IC(50) values calculated
      to be 234, 548 and 209 microg/ml, respectively. This data suggests an effect of
      these extracts on the function of VGCCs in these cells. Furthermore, we found
      similar effects using a fluorescence laser imaging plate reader (FLIPR) that
      allows simultaneous measurement of real-time fluorescence in a multi-well plate.
      Our results indicate that the dichloromethane extract of E. bignoniiflora and the
      methanolic extract of E. vespertilio show considerable promise as antagonists of
      neuronal VGCCs. Further analysis is required to characterise the function of the
      bioactive constituents in these extracts and determine their selectivity on VGCC
      subtypes.

PMID- 11988394
TI  - Optimized conditions for MDCK permeability and turbidimetric solubility studies
      using compounds representative of BCS classes I-IV.
AB  - The solubility enhancing effects of various excipients, including their
      compatibility with in vitro permeability (P(app)) systems, was investigated using
      drugs representative of Biopharmaceutics Classification System (BCS) classes I
      IV. Turbidimetric solubility determination using nephelometry and transport
      experiments using MDCK Strain I cell monolayers were employed. The highest usable
      concentration of each excipient [dimethyl sulfoxide (DMSO), ethanol,
      hydroxypropyl-beta-cyclodextrin (HPCD), and sodium taurocholate] was determined
      by monitoring apical (AP) to basolateral (BL) [14C]mannitol apparent permeability
      (P(app)) and the transepithelial electrical resistance (TEER) in transport
      experiments done at pH 6.0 and 7.4. The excipients were used in conjunction with
      compounds demonstrating relatively low aqueous solubility (amphotericin B,
      danazol, mefenamic acid, and phenytoin) in order to obtain a drug concentration
      >50 microM in the donor compartment. The addition of at least one of the selected
      excipients enhanced the solubility of the inherently poorly soluble compounds to
      >50 microM as determined via turbidimetric evaluation at pH 6.0 and 7.4. Ethanol
      and DMSO were found to be generally disruptive to the MDCK monolayer and were not
      nearly as useful as HPCD and sodium taurocholate. Sodium taurocholate (5 mM) was
      compatible with MDCK monolayers under all conditions investigated. Additionally,
      a novel in vitro system aimed at more accurately simulating in vivo conditions,
      i.e., a pH gradient (6.0 AP/7.4 BL), sodium taurocholate (5 mM, AP), and bovine
      serum albumin (0.25%, BL), was shown to generate more reliable P(app) values for
      compounds that are poorly soluble and/or highly protein bound.

PMID- 11988395
TI  - In situ, real time observation of the disintegration of paracetamol tablets in
      aqueous solution by magnetic resonance imaging.
AB  - The disintegration behavior of paracetamol tablets was studied by magnetic
      resonance imaging (MRI) using the Snapshot FLASH method. The total time of the
      single experiment is 425 ms and allows the study of the disintegration process in
      real time. The study was carried out in vitro under acidic gastric pH conditions
      and may help to predict the behavior of paracetamol tablets in the stomach after
      oral administration. It was shown that in spite of identical conditions, the
      disintegration of the tablets under study was different. The distribution of
      protons of 4-(N-acetyl)aminophenol within the paracetamol tablet was shown to be
      homogeneous. The study was carried out in a non-destructive way by the SPI MRI
      method.

PMID- 11988396
TI  - Determination of the free/included piroxicam ratio in cyclodextrin complexes:
      comparison between UV spectrophotometry and differential scanning calorimetry.
AB  - Few analytical techniques allow to evaluate the inclusion yield of cyclodextrin
      drug complexes, because most manufacturing processes give amorphous products. In
      this study, we have developed an alternative method to differential scanning
      calorimetry, to accurately determine the free/complexed piroxicam ratio by UV
      spectroscopy. This method is based on the differential solubility of the
      piroxicam-beta-cyclodextrin 1:2.5 mol/mol complex in water-acetonitrile (1:1,
      v/v) (Solvent A) or in anhydrous acetonitrile (Solvent B), both containing 0.05 M
      HCl. In anhydrous acetonitrile, beta-cyclodextrin is insoluble and the included
      drug remains entrapped, allowing the free piroxicam determination, while with 50%
      of water, the complex is totally dissolved, allowing the determination of the
      total guest content. This method was validated for linearity, precision and
      accuracy. The presence of cyclodextrin does not influence the assays, but more
      than 0.5% of water in Solvent B significantly affects the determination of the
      free piroxicam content. In comparison with differential scanning calorimetry,
      both detectability and precision were improved. It is now possible to analyse
      complexes with an inclusion purity greater than 99%.

PMID- 11988397
TI  - PLGA-based microparticles: elucidation of mechanisms and a new, simple
      mathematical model quantifying drug release.
AB  - The two major aims of this study were: (i) to elucidate the underlying release
      mechanisms from drug-loaded, erodible microparticles based on poly(lactic-co
      glycolic acid) (PLGA) showing biphasic drug release behavior: an initial 'burst'
      effect, followed by a zero order release phase; and (ii) to develop a new, simple
      mathematical model that allows the quantitative description of the observed in
      vitro drug release patterns from this type of delivery system. PLGA-based
      microparticles offer various advantages, such as the possibility to control the
      resulting drug release rate accurately over prolonged periods of time, easiness
      of administration (e.g., by stereotaxic injection), good biocompatibility and
      complete erosion (avoiding the removal of empty remnants). Consequently, the
      practical importance of these advanced drug delivery systems is remarkably
      increasing. However, only little knowledge is yet available concerning the
      processes controlling the release rate of the drug out of these devices. Various
      chemical and physical phenomena are involved, rendering the identification of the
      crucial mechanisms and the mathematical description of the resulting drug release
      kinetics difficult. In the present study, different physicochemical
      characterization methods (e.g., DSC, SEM, SEC, particle size analysis) were used
      to monitor the changes occurring within anticancer drug-loaded PLGA
      microparticles upon exposure to phosphate buffer pH 7.4. Based on these
      experimental findings, the most important underlying drug release rate
      controlling mechanisms were identified and a new mathematical model was developed
      that allows the quantitative description of the resulting release patterns.

PMID- 11988398
TI  - Progress in the proxifan class: heterocyclic congeners as novel potent and
      selective histamine H(3)-receptor antagonists.
AB  - Histamine H(3) receptors are critically involved in the pathophysiology of
      several disorders of the central nervous system (CNS). Among other families of
      H(3)-receptor ligands, the proxifan class has recently been described to contain
      numerous potent histamine H(3)-receptor antagonists, e.g. ciproxifan or
      imoproxifan. In the present study, we report on the design of novel heterocyclic
      proxifan analogues and their antagonist potencies at histamine H(3) receptors.
      The new compounds were tested for in vitro and in vivo H(3)-receptor antagonist
      potencies in different species as well as for H(3)-receptor selectivity vs. H(1)
      and H(2) receptors. In vitro, all compounds investigated proved to be potent H(3)
      receptor antagonists in the rat as well as in the guinea-pig. In addition, they
      showed good to high oral CNS potency in vivo in mice. Especially, oxadiazole
      derivatives 24-26 displayed nanomolar antagonist activity in vitro and high
      potency in vivo (ED(50)=0.47-0.57 mg/kg). The results show that the additional
      heteroaromatic moieties might act as bioisosteres of the ketone or oxime moieties
      of ciproxifan or imoproxifan, respectively, and might cause divergent
      pharmacokinetic properties. Thus, these novel H(3)-receptor antagonists are
      interesting leads for further development.

PMID- 11988399
TI  - Conformation and ion-binding of oligonucleotides.
AB  - The effective charge and the conformation of oligonucleotides may influence their
      pharmaceutical properties. Therefore, a method based on the convective diffusion
      process was used to measure both the diffusion coefficient and the effective
      charge number of four oligonucleotides with different chain lengths.
      Determinations were carried out at physiological ionic strength and at two
      temperatures, 20 and 40 degrees C. The results indicate that the longer
      oligonucleotides, i.e. number of nucleotides in the molecule from 15 to 30, are
      strongly ion-paired (75-80%) and the shorter oligonucleotide (seven nucleotides)
      is only ca. 50% ion-paired. The extent of ion-binding was not dependent on
      temperature. The conformation of the oligonucleotides appeared to be fairly
      compact in 0.15 M NaCl solution. The compact conformation and strong ion-pairing
      may influence the pharmacokinetics of oligonucleotides, possibly facilitating
      distribution into tissues.

PMID- 11988400
TI  - Thiolated polymers: self-crosslinking properties of thiolated 450 kDa
      poly(acrylic acid) and their influence on mucoadhesion.
AB  - This study examined the rheological and mucoadhesive properties of a self
      crosslinking anionic thiolated polymer in vitro. Mediated by a carbodiimide, L
      cysteine was covalently bound to poly(acrylic acid) of 450 kDa molecular mass.
      The resulting thiolated polymers (conjugates I and II) contained 90.5+/-15.8 and
      511.6+/-52 micromol thiol groups per gram polymer, respectively (mean+/-S.D.,
      n=3). The amount of covalently attached cysteine was therefore dependent on the
      concentration of carbodiimide used for the coupling reaction. Both conjugates
      (3%, m/v) were capable of forming inter- and/or intramolecular disulfide bonds in
      100 mM phosphate buffer pH 6.8. Consequently, the apparent viscosity of
      conjugates I and II increased 12- and 10-fold, respectively, within 24 h of
      incubation at 37 degrees C. Further, rheological synergy was observed by mixing
      equal volumes of polymer (unmodified as well as modified) with a mucin solution.
      A six-fold increase in viscosity immediately after mixing could be observed for
      the conjugate II/mucin mixture. This clearly indicates the high interaction
      potential of self-crosslinking thiomers with the mucus gel layer. Mucoadhesion
      studies confirmed the rheological results. Tablets based on conjugate II remained
      attached on freshly excised porcine mucosa for about 25 times longer than the
      corresponding controls, which is the longest time of mucoadhesion ever found
      among anionic thiomers. Due to the results of the present study, self
      crosslinking thiolated poly(acrylates) of 450 kDa represent very promising
      excipients for the development of various mucoadhesive drug delivery systems.

PMID- 11988401
TI  - Regulation mechanisms of intestinal secretion: implications in nutrient
      absorption.
AB  - Intestinal secretion is a normal phenomenon, indispensible to solubilize and
      dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins
      and certain drugs may disrupt the proabsorptive status maintained by the small
      intestine under physiologic conditions. Hormones found in nervous and specialized
      intestinal enterochromaffin cells are responsible, in part, for secretion of
      fluid into the lumen. Afferent vagal nerve impulses mediated by 5
      hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and
      substance P are the major agents of secretory stimulation. Toxins from pathogenic
      bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory
      response and a chain of events involving cGMP and cAMP which result in chloride
      secretion, coupled to sodium and fluid efflux into the lumen. If secretion is
      unchecked by natural mechanisms or medications, the consequences are diarrhea,
      with potential dehydration, hyponatremia and ultimately death. Introduction of
      absorbable nutrients in the intestinal lumen has a major antisecretory action,
      both by a nutrient-gene interaction and by proabsorptive hormone expression. In
      additon, during the absorptive process water is carried into the enterocyte
      together with solutes. Hydrolysis-resistant peptides of dietary origin and
      ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal
      system has a variety of antisecretory or proabsorptive hormonal and protein
      agonists that balance the outflow of fluid and electrolytes. The more extensively
      studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor
      (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in
      secretion by activating cGMP. The intracellular concentration of NO may regulate
      the absorptive/secretory status of the small intestine, either stimulating
      absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist
      drugs and other pharmacologic agents have been clinically tried for the treatment
      of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.

PMID- 11988402
TI  - Antioxidative effects of lovastatin in cultured human endothelial cells.
AB  - The effects of lovastatin on glutathione peroxidase activity, hydrogen peroxide
      consumption, [3H]cholesterol uptake and [14C]acetate incorporation were
      investigated in cultured human endothelial cells. Treatment of endothelial cells
      with lovastatin in a medium without serum for 4 hr significantly increased both
      glutathione peroxidase activity and hydrogen peroxide consumption. This treatment
      also significantly inhibited cholesterol synthesis and cholesterol
      esterification. However, lovastatin stimulated cholesterol uptake by the cells.
      These alterations produced by lovastatin continued up to 24 hr. When serum was
      present in the culture medium, only decreased cholesterol synthesis and
      esterification were detected. We suggest that the in vitro antioxidative ability
      of lovastatin resulted, in part at least, from its activating effect on
      glutathione peroxidase, its stimulative effect on the ability of endothelial cell
      to scavenge H(2)O(2), and its hypolipidemic effect.

PMID- 11988403
TI  - Dietary fish oil reverse epididymal tissue adiposity, cell hypertrophy and
      insulin resistance in dyslipemic sucrose fed rat model small star, filled.
AB  - The present work was designed to assess the possible benefits of (7% w/w) dietary
      fish oil in reversing the morphological and metabolic changes present in the
      adipose tissue of rats fed an SRD for a long time. With this purpose, in the
      epididymal fat tissue, we investigated the effect of dietary fish oil upon: i)
      the number, size and distribution of cells, ii) the basal and stimulated
      lipolysis, iii) the lipoprotein lipase (LPL) and the glucose 6-phosphate
      dehydrogenase activities, and iv) the antilipolytic action of insulin. The study
      was conducted on rats fed an SRD during 120 days with fish oil being isocaloric
      substituted for corn oil for 90-120 days in half the animals. Permanent
      hypertriglyceridemia, insulin resistance and abnormal glucose homeostasis were
      present in the rats before the source of fat in the diet was replaced. The major
      new findings of this study are the following: i) Dietary fish oil markedly
      reduced the fat pads mass, the hypertrophy of fat cells and improved the altered
      cell size distribution. ii) The presence of fish oil in the diet corrected the
      inhibitory effect of high sucrose diet upon the antilipolytic action of insulin,
      reduced the "in vitro" enhanced basal lipolysis and normalized isoproterenol
      stimulated lipolysis. Fat pads lipoprotein lipase activity decreased reaching
      values similar to those observed in age-matched controls fed a control diet (CD).
      These effects were not accompanied by any change in rat body weight. All these
      data suggest that the dyslipemic rats fed a moderate amount of dietary fish oil
      constitute a useful animal model to study diet-regulated insulin action.

PMID- 11988404
TI  - Metallothionein mRNA levels are influenced by dietary cyclodextrins in rats.
AB  - The relationship between metallothionein mRNA levels and the amounts of copper
      and zinc in liver, kidney and small intestine by feeding dietary cyclodextrin was
      examined in growing Wistar rats. alpha-, beta- or gamma-cyclodextrin was fed at
      50 g/kg of diet for a 7-days period (ad libitum). After feeding, the liver zinc
      of rats fed beta-cyclodextrin was greater than those of rats fed the other three
      diets. Copper accumulated in kidney of rats fed alpha- or beta-cyclodextrin.
      Copper content in the small intestine did not show any alterations among rats fed
      all kinds of diets. The cyclodextrin-supplemented diets were ineffective in zinc
      content in every organ. There was the greatest level of copper in serum of rats
      fed beta-cyclodextrin, whereas the highest level of serum zinc was observed in
      rats fed gamma-cyclodextrin diet. Northern blot analysis demonstrated that
      dietary beta- and gamma-cyclodextrins, but not alpha-cyclodextrin markedly
      increased the metallothionein mRNA in the liver, whereas small intestinal
      metallothionein mRNA levels were markedly decreased. Kidney metallothionien mRNA
      levels were raised appreciably by all dietary cyclodextrin intakes.
      Metallothionein gene expressions in liver, kidney and small intestine were not
      proportional to liver and serum copper or zinc levels in those tissues. These
      results suggest that regulation of the metallothionein mRNA levels may at least
      partly involved with the accumulation of metals as copper in liver and kidney of
      rats fed cyclodextrins.

PMID- 11988405
TI  - The Syrian golden hamster strain LPN: a useful animal model for human
      cholelithiasis.
AB  - The purpose of this study was to specify the main mechanisms at the origin of
      gallstone formation in very young (5-week old) or young adult (9-week old) LPN
      hamsters fed a sucrose-rich (normal lipid) lithogenic diet for one and four
      weeks, respectively. It was also to compare these mechanisms in the two strains
      of hamsters (LPN and Janvier) or when an anti-lithiasic diet was given by
      substituting 10% of the sucrose by beta cyclodextrin. The LPN strain of hamsters
      showed a very high incidence of cholesterol gallstones (73%) after receiving the
      lithogenic diet. The gallstone formation is very rapid and occurs in less than
      one week in very young hamsters which show a high cholesterol synthesis rate in
      the liver. The cholesterol and phospholipid concentrations in the bile,
      cholesterol saturation index (CSI) and hydrophobic index (HI) increased
      significantly, concomitantly with a higher liver cholesterol synthesis in very
      young hamsters and with a lower bile acid synthesis (neutral pathway: cholesterol
      7alpha-hydroxylase, CYP7A1 and acidic pathway: sterol 27 hydroxylase, CYP27A1) in
      young adult hamsters. No significant changes in the lipoprotein receptor
      expression (LDLr, SR-BI) were observed after feeding the lithogenic diet. Adding
      ten per cent beta-cyclodextrin, a cyclic oligosaccharide that binds cholesterol
      and bile acids to the lithogenic diet at the expense of sucrose, induced a
      decrease in cholesterol bile secretion and in the CSI and HI and prevented
      cholesterol gallstone formation. Similarly, another strain of Syrian Golden
      hamsters (" Janvier ") which originally exhibited a smaller bile cholesterol
      concentration, lower liver cholesterol synthesis and higher CYP7A1/CYP27A1
      activity ratio did not carry cholesterol gallstones when fed the lithogenic diet.
      The main parameters always found at the origin of cholelithiasis in the Hamster
      are discussed: a higher hepatic cholesterogenesis (HMGCoAR), a higher
      HMGCoAR/CYP7A1 activity ratio, a lower cholesterol ester storage capacity, a
      higher CYP27A1/CYP7A1 activity ratio correlated to a higher cholesterol secretion
      in the bile and higher CSI and HI. In LPN hamsters, the incidence of cholesterol
      gallstones is nil when CSI + HI < 0.8 and positive for CSI + HI > 0.9. An overall
      comparison of the data obtained in LPN Hamsters and in Man suggests that this
      hamster strain appears to be an interesting model for human cholelithiasis.

PMID- 11988406
TI  - Decreased food intake rather than zinc deficiency is associated with changes in
      plasma leptin, metabolic rate, and activity levels in zinc deficient rats( small
      star, filled).
AB  - This study investigated the hypothesis that the reduced food intake and poor
      weight gain in zinc deficient rats is due to: increased plasma leptin
      concentration, increased physical activity and/or increased metabolic rate.
      Weanling rats were assigned to three groups: controls fed ad libitum (C), zinc
      deficient (ZD), and pair-fed controls (PF), and tested in a metabolic chamber and
      activity monitor at baseline and weekly for four weeks. At the end of the study,
      all groups were compared for differences in plasma leptin concentrations. ZD and
      PF animals had markedly reduced food intake and weight gain. ZD had reduced
      stereotypic and locomotor activity compared to PF animals and both groups
      demonstrated an abolished peri-nocturnal activity spike and were much less active
      than controls. This was associated with a reduced total metabolic rate by day 30:
      ZD (0.73 +/- 0.07 kcal/hr, p = 0.0001) and PF (0.83 +/- 0.06 kcal/hr, p = 0.0001)
      groups vs. controls (1.82 +/- 0.09 kcal/hr). Plasma leptin concentrations in ZD
      (1.55 +/- 0.06 &mgr;g/L) were lower than controls (2.01 +/- 0.18 &mgr;g/L, p <
      0.03), but neither ZD nor controls were statistically different from PF (1.68 +/-
      0.05 &mgr;g/L). Both low leptin concentrations and low metabolic rates in the ZD
      and PF rats were associated with decreased food intake rather than zinc
      deficiency. The reduced food intake and poor weight gain observed in zinc
      deficient rats could not be explained by elevated leptin concentrations,
      hypermetabolism, or increased activity. Low serum leptin concentrations,
      hypometabolism, and decreased activity are more likely the result of the anorexia
      of zinc deficiency.

PMID- 11988407
TI  - High molecular weight water-soluble chitosan protects against apoptosis induced
      by serum starvation in human astrocytes.
AB  - The effect of high molecular weight water-soluble chitosan (WSC) on serum
      starvation-induced apoptosis in human astrocytes (CCF-STTG1 Cells) was
      investigated. WSC, having an average molecular weight of 300 kDa and a degree of
      deacetylation over 90%, can be produced using a simple multi-step membrane
      separation process. Serum starvation led to growth arrest, rounding up of cells
      and appearance of p53 bands. Prolonged (48 h) incubation in serum starved medium
      led to cell detachment and death. WSC significantly protected the serum
      starvation-induced cellular rounding up and protected the serum starvation
      induced cell death as tested by flow cytometry. WSC also protected serum
      starvation-induced p53 activation as determined by Western blot. These results
      suggest that WSC may prevent serum starvation-induced apoptosis of CCF-STTG1
      cells via p53 inactivation.

PMID- 11988408
TI  - The NICHD Women's Contraceptive and Reproductive Experiences Study: methods and
      operational results.
AB  - PURPOSE: This paper presents methods and operational results of a population
      based case-control study examining the effects of oral contraceptive use on
      breast cancer risk among white and black women aged 35-64 years in five U.S.
      locations. METHODS: Cases were women newly diagnosed with breast cancer during
      July 1994 through April 1998. Controls were identified through random digit
      dialing (RDD) using unclustered sampling with automated elimination of nonworking
      numbers. Sampling was density-based, with oversampling of black women. In-person
      interviews were conducted from August 1994 through December 1998. Blood samples
      were obtained from subsets of cases and controls, and tissue samples were
      obtained from subsets of cases. A computerized system tracked subjects through
      study activities. Special attention was devoted to minimizing exposure
      misclassification, because any exposure-disease associations were expected to be
      small. RESULTS: An estimated 82% of households were screened successfully through
      RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682
      controls (3021 whites; 1661 blacks). Interview response rates for cases and
      controls were 76.5% and 78.6%, respectively, with lower rates for black women and
      older women. CONCLUSIONS: The methodologic details of this large collaboration
      may assist researchers conducting similar investigations.

PMID- 11988409
TI  - Serological evidence of endemic waterborne cryptosporidium infections.
AB  - PURPOSE: Cryptosporidium oocysts are commonly detected in surface-derived
      drinking water, however, the public health significance of these findings is
      unclear. This study compared the evidence of prior Cryptosporidium infection for
      people drinking water derived from surface versus ground water sources. METHODS:
      This study measured serological responses to two Cryptosporidium antigen groups
      for blood donors from two midwestern United States cities with different drinking
      water sources: filtered and chlorinated river water receiving agricultural and
      domestic sewage upstream versus chlorinated water from an underground aquifer.
      Initial and nine-month paired serological responses to two Cryptosporidium
      antigen groups were compared. RESULTS: Initially, donors from the surface water
      city had a higher relative prevalence (RP) of a serological response (54% vs.
      38%, RP = 1.39 (1.21,1.60)). Donors with a detectable baseline response who
      resided in the surface water city had a higher relative risk (RR) of an increased
      intensity of response on the follow-up blood draw (15/17-kDa, 40/100 vs. 11/100,
      RR = 3.78 (1.89,7.58)), (27-kDa 38/100 vs. 18/100, RR = 2.07 (1.31,3.25)). Donors
      with no baseline response to the 15/17-kDa marker who resided in the surface
      water city also had a higher risk of serconversion (38/100 vs. 14/100, RR = 2.63
      (1.78,3.91)). CONCLUSIONS: These rates of both background and drinking water
      related Cryptosporidium infections are substantially higher than previously
      estimated, however, the risk of illness from infection may be lower.

PMID- 11988410
TI  - Hyperhomocyst(e)inemia and hemostatic factors: the atherosclerosis risk in
      communities study.
AB  - PURPOSE: To determine whether homocyst(e)ine (H(e)) is related to hemostatic
      factors in a population-based sample without evidence of cardiovascular disease.
      METHODS: A subsample of 660 participants--67 African-American women, 53 African
      American men, 201 white women, and 339 white men--was selected from the
      Atherosclerosis Risk in Communities Study baseline cohort. This was based on
      carotid intimal-medial wall thickness above the 90th percentile or below the 75th
      percentile of the population distribution, assessed by B-mode ultrasonography.
      Unadjusted and multivariable-adjusted associations between fasting plasma H(e)
      and the hemostatic factors fibrinogen, factor VII:c, factor VIII:c, protein C
      antigen, hematocrit, platelet count, beta-thromboglobulin (beta-TG), tissue
      plasminogen activator (tPA), PAI-1, D-dimer, and lipoprotein[a] were examined.
      RESULTS: Mean age-adjusted H(e) was positively, albeit weakly, correlated with
      beta-TG, tPA, hematocrit, D-dimer and PAI-1; inversely correlated with protein C;
      and was higher in smokers, men and African-Americans. In multivariable
      regression, beta-TG, tPA, and factor VII:c were positively associated with H(e),
      as well as age, black race, male sex, and current cigarette smoking. CONCLUSIONS:
      These cross-sectional data for a biracial group of middle-aged individuals
      suggest that H(e) levels falling below values consistent with homocyst(e)inemia
      are associated with several prothrombotic factors after adjustment for
      sociodemographic factors. If H(e) change is antecedent to altered hemostasis, FDA
      mandated fortification of grain products with folic acid for prevention of fetal
      neural tube defects may lead to both reduced plasma H(e) levels and improved
      hemostatic profiles.

PMID- 11988411
TI  - Weight change in relation to natural menopause and other reproductive and
      behavioral factors in Japanese women.
AB  - PURPOSE: To evaluate the effect of menopause on weight change in Japanese women.
      METHODS: Community-based sample of 828 Japanese women who were premenopausal and
      aged 40 to 54 years completed a self-administered questionnaire asking
      information on demographic factors, body size, reproductive history and dietary
      and behavioral factors in 1992. They responded to a follow-up questionnaire
      asking weight and menopausal status in 1998. RESULTS: Women gained weight
      modestly, on average, 0.17 kg during the 6-year study period. Weight gain was
      significantly higher in women who remained premenopausal at follow-up than those
      who had natural menopause during the study period. Weight gain was significantly
      associated with early menarche in women who had natural menopause and with high
      parity in women remained premenopausal. CONCLUSION: Reproductive factors rather
      than sociodemographic and behavioral factors appeared to be associated with
      weight change during the perimenopausal period. Onset of menopause may diminish
      weight gain. In contrast, early menarche and high parity showed relationships
      with weight gain.

PMID- 11988412
TI  - Reliability of self-reported reproductive factors and childhood social class
      indicators in a case-control study in women.
AB  - PURPOSE: Reproductive factors are often evaluated in epidemiologic interview
      studies as risk factors for diseases in women. Similarly, childhood social class
      has been implicated in the etiology of several diseases. Nevertheless, questions
      related to these factors have not been thoroughly evaluated for test-retest
      reliability. This research measured the test-retest reliability of reproductive
      and childhood social class variables, and determined whether reliability differed
      by case-control status, age, educational level, time between interviews, and
      interviewer-rated quality of the interview. METHODS: Subjects were participants
      in a population-based case-control in-person interview study of Hodgkin's disease
      in northern California women. Twenty-four cases and 22 controls were
      reinterviewed by telephone between 1992 and 1995, with an average interval of 8
      months between interviews. Reliability was assessed using kappa or intraclass
      correlation coefficients; mean reliability coefficients and 95% confidence
      intervals (CIs) were estimated using the bootstrap method. RESULTS: Reliability
      was excellent for all variables (reliability coefficients between 0.76 and 0.96)
      and did not differ by case-control status (mean reliability = 0.82 for cases and
      0.84 for controls), age (mean reliability = 0.85 for age < 40 and 0.82 for age >
      or = 40), time between interviews (mean reliability = 0.75 for 0-5 months, 0.88
      for 6-11 months, and 0.87 for 1 year or more), or interviewer-rated quality of
      the validity of the original responses (mean reliability = 0.93 for "not too
      confident" and 0.83 for "confident"). However, reliability was consistently lower
      among less educated women (mean reliability = 0.56 for high school or less and
      0.88 for more than high school), a finding consistent with results of prior
      studies. CONCLUSIONS: These results indicate that questions about reproductive
      experience and childhood social class posed in in-person interviews can be
      answered reliably. However, inclusion of subjects at lower socioeconomic status
      may result in lower reliability for some interview responses.

PMID- 11988413
TI  - Racial differences in factors that influence the willingness to participate in
      medical research studies.
AB  - PURPOSE: The relative absence of racial/ethnic minorities among medical research
      subjects is receiving considerable attention because of recent government
      mandates for their inclusion in all human subject research. We examined racial
      differences in the prevalence of sociocultural barriers as a possible explanation
      for the underrepresentation of African Americans in medical research studies.
      METHODS: During 1998-1999, a total of 198 residents of the Detroit Primary
      Metropolitan Statistical Area (PMSA) participated in a survey that examined
      impediments to participation in medical research studies. Chi square tests and
      logistic regression analyses were used to examine the association between race,
      issues related to trust of medical researchers, and the willingness to
      participate in medical research studies. RESULTS: Study results indicate that
      African Americans and whites differ in their willingness to participate in
      medical research. Racial differences in the willingness to participate in a
      medical research are primarily due to the lower level of trust of medical
      research among African Americans. African American respondents were also somewhat
      less willing to participate if they attribute high importance to the race of the
      doctor when seeking routine medical care, believed that minorities bear most of
      the risks of medical research, and if their knowledge of the Tuskegee Study
      resulted in less trust in medical researchers. CONCLUSION: These data reiterate
      the need for medical researchers to build trusting relationships with minority
      communities. Researchers can begin by acknowledging the previous medical abuse of
      minority research participants, discussing their specific plans to assure the
      protection of study participants, and explaining the need for the participation
      of racial/ethnic minorities including studies that specifically target or that
      are likely to result in disproportionate representation of racial/ethnic
      minorities among study participants.

PMID- 11988414
TI  - Reproduction life history and hip fractures.
AB  - PURPOSE: The present study assesses the association between reproduction and hip
      fractures. METHODS: We used two surveys on elderly Danish twins of both sexes and
      the Danish National Register of Patients. In a cross-sectional study of 2045
      twins aged 75-98 years in 1995, we studied the association between different
      aspects of reproduction and hip fractures leading to hospitalization between 1977
      and 1994. In a prospective study, 3057 twins aged 66-99 years in 1977 were
      followed for a total of 29,112 years, and the association between number of
      children and incidence of hip fractures was investigated. RESULTS: In the cross
      sectional study, as well as the prospective study, we found, for both sexes, that
      having no children was associated with a higher risk of hip fracture compared to
      having at least one child. When excluding persons without children, we found no
      effect of number of birth events/children. In the cross-sectional study, we found
      no effect of birth interval length or age at first birth. For women, we found an
      effect of age at last birth. CONCLUSIONS: No "cost-of-reproduction" in terms of
      hip fractures was observed. On the contrary, we found that having one or more
      children was associated with a lower risk of hip fracture.

PMID- 11988416
TI  - Validation of a five-question survey to assess a child's exposure to
      environmental tobacco smoke.
AB  - PURPOSE: To study the potentially adverse health effects of environmental tobacco
      smoke (ETS) exposure in young children, a short five-question survey was
      developed to identify routine exposure to ETS in a large epidemiological study.
      METHODS: The survey is administered to parents of a healthy cohort of children
      starting at age 3 months. To validate the survey, urinary cotinine levels were
      measured on 50 children from this cohort who were selected based on ETS exposure
      as reported in the survey: 24 with no exposure and 26 with exposure. Cotinine was
      adjusted for creatinine. RESULTS: Overall, children with some form of reported
      ETS exposure had urinary cotinine levels 7.5 times higher than those who were not
      exposed. Analysis of variance shows that mean levels of log transformed cotinine
      in children whose parent(s) smoke in the home, parent(s) who smoke but not in the
      home, and non-smoking parents are 137.13, 75.60, and 43.28 respectively (p =
      0.0009), indicating decreasing levels of cotinine as reported exposure decreases.
      Using a cut-point of 30 ng/mg of cotinine to differentiate unexposed and exposed
      to ETS, we found 80% agreement with our survey. A Spearman's ranked correlation
      coefficient of 0.62 indicates a direct relationship between cotinine and an ETS
      exposure intensity score (p < 0.0001). CONCLUSIONS: These results suggest that
      the 5-question survey reflects the child's exposure to passive smoke and that the
      survey is sensitive to varying levels of exposure.

PMID- 11988415
TI  - The association between gravidity and primary biliary cirrhosis.
AB  - PURPOSE: Primary biliary cirrhosis is an autoimmune disease with female
      predominance that leads to liver failure. The goal of this study was to identify
      reproductive risk factors associated with this disease. METHODS: We compared 182
      cases of PBC with 225 age- and sex-matched friend controls to examine the role of
      reproductive factors. The survey instrument was developed using standardized
      questions obtained from the National Health and Nutrition Examination Survey
      (NHANES) III. RESULTS: A total of 126/182 cases (69%) and 141/225 (62.6%) friend
      controls responded to the survey. More cases than controls reported ever having
      genitourinary infection [adjusted odds ratio (OR) = 2.12, 95% confidence interval
      (CI) 1.01, 4.42] among those without a personal or family history of autoimmune
      disease. The most notable finding was that cases reported significantly more
      pregnancies than controls (p = 0.008). The adjusted OR for each additional
      pregnancy among those without a personal or family history of autoimmune disease
      was 1.40 (95% CI 1.14, 1.7). More controls (24.4%) than cases (16.0%) were
      nulliparous. Cases reported having five or more children (16.0%) with double the
      frequency of controls (8.2%). CONCLUSIONS: The association reported herein,
      between primary biliary cirrhosis and gravidity, is particularly significant
      because of the overwhelming female predominance.

PMID- 11988417
TI  - The reliability of dietary data for self- and next-of-kin respondents.
AB  - BACKGROUND: In case-control studies, recalled dietary data from next-of-kin are
      sometimes used as a surrogate measure of exposure; however, there is limited
      evidence comparing the ability of study participants and next-of-kin surrogates
      for the reliability of their responses with respect to past dietary recall.
      METHODS: We compared dietary information from 303 subjects who were administered
      a food frequency questionnaire in 1980 with that from 196 of the same subjects
      and 107 next-of-kin of deceased subjects 5 years later, but with reference to
      1980 diet. Agreement between 1980 and 1985 reporting with respect to food groups,
      food preparation methods, and adherence to special diets was primarily assessed
      using the kappa statistic. RESULTS: The concordance between 1980 and 1985
      reporting of specific food groups was generally poor. Regarding various methods
      of cooking meats and the use of different types of cooking fats, next-of-kin
      respondents showed very poor agreement with the reporting of their deceased
      relatives, and within-subject agreement was also poor for frying meats, baking
      meats, and for cooking with margarine and vegetable oil. Subjects and next-of-kin
      were able to reproduce earlier reporting of a special ulcer diet, but not
      diabetic or low-salt diets. Overall, subjects tended to have better agreement
      with their own earlier reporting than did next-of-kin, and spouses were found to
      be more reliable next-of-kin respondents than other relatives. CONCLUSIONS:
      Dietary data collected retrospectively from next-of-kin may be unreliable.

PMID- 11988418
TI  - Regarding "the completeness, validity, and timeliness of AIDS surveillance data".

PMID- 11988420
TI  - Environmental asthma intervention.

PMID- 11988422
TI  - Ethics, human rights, and public health.

PMID- 11988423
TI  - Welfare reform and Latinas' use of perinatal health care.

PMID- 11988425
TI  - Evidence-based medicine and alternative treatments.

PMID- 11988427
TI  - Housing and health.

PMID- 11988428
TI  - Should housing be built on former brownfield sites?

PMID- 11988429
TI  - From woolsorters to mail sorters: anthrax past, present, and future.

PMID- 11988430
TI  - Taking better baby contests seriously.

PMID- 11988431
TI  - America's affordable housing crisis: a contract unfulfilled.
AB  - For many poor Americans, having a decent home and suitable living environment
      remains a dream. This lack of adequate housing is not only a burden for many of
      the poor, but it is harmful to the larger society as well, because of the adverse
      effects of inadequate housing on public health. Not only is the failure to
      provide adequate housing shortsighted from a policy perspective, but it is also a
      failure to live up to societal obligations. There is a societal obligation to
      meet the housing needs of everyone, including the most disadvantaged. Housing
      assistance must become a federally-funded entitlement.

PMID- 11988432
TI  - The human right to adequate housing: a tool for promoting and protecting
      individual and community health.
AB  - The human right to adequate housing is enshrined in international law. The right
      to adequate housing can be traced to the Universal Declaration of Human Rights,
      which was unanimously adopted by the world community in 1948. Since that time,
      the right to adequate housing has been reaffirmed on numerous occasions and
      further defined and elaborated. A key component of this right is habitability of
      housing, which should comply with health and safety standards. Therefore, the
      right to adequate housing provides an additional tool for advocates and others
      interested in promoting healthful housing and living conditions and thereby
      protecting individual and community health.

PMID- 11988433
TI  - The Anthrax Vaccine Program: an analysis of the CDC's recommendations for vaccine
      use.
AB  - The anthrax vaccine was never proved to be safe and effective. It is one cause of
      Gulf War illnesses, and recent vaccinees report symptoms resembling Gulf War
      illnesses. The vaccine's production has been substandard. Without adequate
      evaluation, the Food and Drug Administration recently approved (retrospectively)
      significant changes made to the vaccine's composition since 1990. The vaccine's
      mandatory use for inhalation anthrax is "off-label." A skewed review of the
      vaccine literature by the Centers for Disease Control and Prevention (CDC) led to
      remunerative collaborative research with the army, involving civilian volunteers.
      Despite acknowledging possible fetal harm, the CDC offered the vaccine to
      children and pregnant women. New trends could weaken prelicensure efficacy and
      safety review of medical products intended for biodefense and avoid manufacturer
      liability for their use.

PMID- 11988434
TI  - Rethinking McKeown: the relationship between public health and social change.
AB  - Thomas McKeown was a rhetorically powerful critic, from the inside, of the
      medical profession's mid-20th-century love affair with curative and scientific
      medicine. He emphasized instead the importance of economic growth, rising living
      standards, and improved nutrition as the primary sources of most historical
      improvements in the health of developed nations. This interpretation failed to
      emphasize the simultaneous historical importance of an accompanying
      redistributive social philosophy and practical politics, which has characterized
      the public health movement from its 19th-century origins. Consequently, the
      current generation of public health practitioners are having to reconstruct such
      a politics and practice following its virtual dismantlement during the last 2
      decades of the 20th century.

PMID- 11988435
TI  - The McKeown thesis: a historical controversy and its enduring influence.
AB  - The historical analyses of Thomas McKeown attributed the modern rise in the world
      population from the 1700s to the present to broad economic and social changes
      rather than to targeted public health or medical interventions. His work
      generated considerable controversy in the 1970s and 1980s, and it continues to
      stimulate support, criticism, and commentary to the present day, in spite of his
      conclusions' having been largely discredited by subsequent research. The ongoing
      resonance of his work is due primarily to the importance of the question that
      underlay it: Are public health ends better served by targeted interventions or by
      broad-based efforts to redistribute the social, political, and economic resources
      that determine the health of populations?

PMID- 11988436
TI  - McKeown and the idea that social conditions are fundamental causes of disease.
AB  - In an accompanying commentary, Colgrove indicates that McKeown's thesis-that
      dramatic reductions in mortality over the past 2 centuries were due to improved
      socioeconomic conditions rather than to medical or public health interventions
      has been "overturned" and his theory "discredited." McKeown sought to explain a
      very prominent trend in population health and did so with a strong emphasis on
      the importance of basic social and economic conditions. If Colgrove is right
      about the McKeown thesis, social epidemiology is left with a gaping hole in its
      explanatory repertoire and a challenge to a cherished principle about the
      importance of social factors in health. We return to the trend McKeown focused
      upon-post-McKeown and post-Colgrove-to indicate how and why social conditions
      must continue to be seen as fundamental causes of disease.

PMID- 11988437
TI  - Home is where the harm is: inadequate housing as a public health crisis.
AB  - Overcrowding and poor-quality housing have a direct relationship to poor mental
      health, developmental delay, heart disease, and even short stature.

PMID- 11988438
TI  - Lead awareness: North Philly Style.
AB  - Lead poisoning in children has been associated with reduced intelligence,
      shortened memory, slowed reaction times, poor hand-eye coordination, and
      antisocial behavior. The cost to society includes not only medical treatment and
      special education but also higher high-school drop-out rates, which are
      associated with crime and low earning potential.

PMID- 11988439
TI  - Making better babies: public health and race betterment in Indiana, 1920-1935.
AB  - In 1920, Indiana's Division of Infant and Child Hygiene inaugurated its first
      Better Babies Contest at the state fair. For the next 12 years, these contests
      were the centerpiece of a dynamic infant and maternal welfare program that took
      shape in Indiana during the decade of the federal Sheppard-Towner act. More than
      just a lively spectacle for fairgoers, these contests brought public health,
      "race betterment," and animal breeding together in a unique manner. This article
      describes one of the most popular expressions of public health and race
      betterment in rural America. It also raises questions about the intersections
      between hereditarian and medical conceptions of human improvement during the
      early 20th century, especially with respect to child breeding and rearing.

PMID- 11988440
TI  - Baxter Street then.

PMID- 11988441
TI  - Anthrax and the wool trade. 1902.

PMID- 11988444
TI  - Relation between housing age, housing value, and childhood blood lead levels in
      children in Jefferson County, Ky.

PMID- 11988445
TI  - Asthma-related limitations in sexual functioning: an important but neglected area
      of quality of life.

PMID- 11988443
TI  - Housing and health: time again for public health action.
AB  - Poor housing conditions are associated with a wide range of health conditions,
      including respiratory infections, asthma, lead poisoning, injuries, and mental
      health. Addressing housing issues offers public health practitioners an
      opportunity to address an important social determinant of health. Public health
      has long been involved in housing issues. In the 19th century, health officials
      targeted poor sanitation, crowding, and inadequate ventilation to reduce
      infectious diseases as well as fire hazards to decrease injuries. Today, public
      health departments can employ multiple strategies to improve housing, such as
      developing and enforcing housing guidelines and codes, implementing "Healthy
      Homes" programs to improve indoor environmental quality, assessing housing
      conditions, and advocating for healthy, affordable housing. Now is the time for
      public health to create healthier homes by confronting substandard housing.

PMID- 11988446
TI  - Challenges faced by homeless sexual minorities: comparison of gay, lesbian,
      bisexual, and transgender homeless adolescents with their heterosexual
      counterparts.
AB  - OBJECTIVES: The goal of this study was to identify differences between gay,
      lesbian, bisexual, and transgender (GLBT) homeless youths and their heterosexual
      counterparts in terms of physical and mental health difficulties. METHODS: A
      sample of 84 GLBT adolescents was matched in regard to age and self-reported
      gender with 84 heterosexual adolescents. The 2 samples were compared on a variety
      of psychosocial variables. RESULTS: GLBT adolescents left home more frequently,
      were victimized more often, used highly addictive substances more frequently, had
      higher rates of psychopathology, and had more sexual partners than heterosexual
      adolescents. CONCLUSIONS: Homeless youths who identify themselves as members of
      sexual minority groups are at increased risk for negative outcomes.
      Recommendations for treatment programs and implications for public health are
      discussed.

PMID- 11988447
TI  - Emergency department use among the homeless and marginally housed: results from a
      community-based study.
AB  - OBJECTIVES: This study examined factors associated with emergency department use
      among homeless and marginally housed persons. METHODS: Interviews were conducted
      with 2578 homeless and marginally housed persons, and factors associated with
      different patterns of emergency department use were assessed in multivariate
      models. RESULTS: Findings showed that 40.4% of respondents had 1 or more
      emergency department encounters in the previous year; 7.9% exhibited high rates
      of use (more than 3 visits) and accounted for 54.5% of all visits. Factors
      associated with high use rates included less stable housing, victimization,
      arrests, physical and mental illness, and substance abuse. Predisposing and need
      factors appeared to drive emergency department use. CONCLUSIONS: Efforts to
      reduce emergency department use among the homeless should be targeted toward
      addressing underlying risk factors among those exhibiting high rates of use.

PMID- 11988448
TI  - Clean indoor air: advances in California, 1990-1999.
AB  - OBJECTIVES: This study assessed progress in achieving clean indoor air in
      California. METHODS: Data were from large, cross-sectional population-based
      surveys (1990-1999). RESULTS: Indoor workers reporting smoke-free workplaces
      increased from 35.0% (95% confidence interval [CI] = 33.7, 36.3) in 1990 to 93.4%
      (95% CI = 92.6, 94.2) in 1999. Exposure of nonsmoking indoor workers to
      secondhand tobacco smoke decreased from 29.0% (95% CI = 27.2, 30.8) to 15.6% (95%
      CI = 14.1, 17.1). Adults with smoke-free homes increased from 37.6 % (95% CI =
      35.1, 40.1) in 1992 to 73.7% (95% CI = 73.2, 74.2) in 1999; nearly half of
      smokers in 1999 had smoke-free homes. In 1999, 82.2% (95% CI = 81.5, 82.9) of
      children and adolescents (0-17 years) had smoke-free homes, up from 38.0% (95% CI
      = 35.1, 40.9) in 1992. CONCLUSIONS: California's advances highlight an important
      opportunity for tobacco control.

PMID- 11988449
TI  - Unraveling the ecology of risks for early childhood asthma among ethnically
      diverse families in the southwest.
AB  - OBJECTIVES: We describe the prevalence of asthma risk factors within
      racial/ethnic and language groups of infants participating in an intervention
      study for reducing chronic asthma. METHODS: Low-income children aged 9 to 24
      months with 3 or more episodes of wheezing illness were enrolled. Baseline
      information included family and medical histories, allergic status, environmental
      exposures, emotional environment, and caregiver psychosocial resources. RESULTS:
      Racial/ethnic and language groups-European Americans, African Americans, high
      acculturated Hispanics, and low-acculturated Hispanics-showed different patterns
      of risk factors for childhood asthma, with low-acculturated Hispanics showing the
      most distinctive pattern. CONCLUSIONS: Patterns of covariation of biological and
      psychosocial risk factors for childhood asthma were associated with racial/ethnic
      and language status among urban, low-income children.

PMID- 11988450
TI  - Effects of participation in the WIC program on birthweight: evidence from the
      National Longitudinal Survey of Youth. Special Supplemental Nutrition Program for
      Women, Infants, and Children.
AB  - OBJECTIVES: This study sought to estimate the impact on birthweight of maternal
      participation in the Special Supplemental Nutrition Program for Women, Infants,
      and Children (WIC). METHODS: WIC estimates were based on sibling models
      incorporating data on children born between 1990 and 1996 to women taking part in
      the National Longitudinal Survey of Youth. RESULTS: Fixed-effects estimates
      indicated that prenatal WIC participation was associated with a 0.075 unit
      difference (95% confidence interval [CI] = -0.007, 0.157) in siblings' logged
      birthweight. At the 88-oz (2464-g) low-birthweight cutoff, this difference
      translated into an estimated impact of 6.6 oz (184.8 g). CONCLUSION: Earlier WIC
      impact estimates may have been biased by unmeasured characteristics affecting
      both program participation and birth outcomes. Our approach controlled for such
      biases and revealed a significant positive association between WIC participation
      and birthweight.

PMID- 11988451
TI  - Role of Black churches in health promotion programs: lessons from the Los Angeles
      Mammography Promotion in Churches Program.
AB  - OBJECTIVES: This article assesses pastor-level factors that affect the successful
      recruitment and implementation of community-based health promotion programs in
      Black churches. METHODS: Semistructured interviews with 16 pastors of Black
      churches were analyzed for content. RESULTS: We found that although the
      involvement of Black pastors in an array of secular activities makes them open to
      participate in health programs, their overcommitment to other issues can
      negatively influence their ability to participate. Second, although Black pastors
      appreciate being included in and benefiting from health research, minorities'
      history of being underserved and exploited can lead to suspiciousness and
      reluctance to participate. CONCLUSIONS: Our findings suggest that those
      interested in developing church-based health programs in the Black community must
      be attuned to how the same factors can both facilitate and hinder a program's
      development.

PMID- 11988452
TI  - Relationship between patients' perceptions of disadvantage and discrimination and
      listing for kidney transplantation.
AB  - OBJECTIVES: This study explored wait-listing decisions among African American and
      White men and women eligible for kidney transplants, focusing on lifetime
      experiences of race and sex discrimination as a possible influence. METHODS:
      Patient records from 3 Baltimore-area hemodialysis units were reviewed, and
      semistructured face-to-face interviews were conducted with transplant-eligible
      patients and with unit staff members. RESULTS: African American patients reported
      more racial discrimination, and women reported more sex discrimination. Women and
      older patients were less likely to be placed on the waiting list, as were
      patients with previous experiences of racial discrimination. Discrimination
      measures predicted list access more strongly than patient race. CONCLUSIONS:
      Lifetime experience of and response to discrimination may contribute to race and
      sex differences in access to care and should be included in research on health
      care disparities.

PMID- 11988453
TI  - HIV and AIDS risk behaviors among female jail detainees: implications for public
      health policy.
AB  - OBJECTIVES: We examined the sexual and injection drug use HIV and AIDS risk
      behaviors of female jail detainees. METHODS: The sample (n = 948) was stratified
      by charge type (felony vs misdemeanor) and race/ethnicity (African American, non
      Hispanic White, Hispanic, other). RESULTS: Non-Hispanic White women, women
      arrested for less serious charges, women who had prior arrests, women arrested on
      drug charges, and women with severe mental disorders were at especially high risk
      for sexual and injection drug transmission of HIV and AIDS. CONCLUSIONS: Many
      women at risk for HIV and AIDS--women who use drugs, women who trade sex for
      money or drugs, homeless women, and women with mental disorders--eventually will
      cycle through jail. Because most jail detainees return to their communities
      within days, providing HIV and AIDS education in jail must become a public health
      priority.

PMID- 11988454
TI  - Tuberculosis screening among foreign-born persons applying for permanent US
      residence.
AB  - OBJECTIVES: This study sought to determine adherence of physicians to
      tuberculosis (TB) screening guidelines among foreign-born persons living in the
      United States who were applying for permanent residency. METHODS: Medical forms
      of applicants from 5 geographic areas were reviewed, along with information from
      a national physician database on attending physicians. Applicant and
      corresponding physician characteristics were compared among those who were and
      were not correctly screened. RESULTS: Of 5739 applicants eligible for screening
      via tuberculin skin test, 75% were appropriately screened. Except in San Diego,
      where 11% of the applicants received no screening, most of the inappropriate
      screening resulted from the use of chest x-rays as the initial screening tool.
      CONCLUSIONS: Focused physician education and periodic monitoring of adherence to
      screening guidelines are warranted.

PMID- 11988455
TI  - Heat wave morbidity and mortality, Milwaukee, Wis, 1999 vs 1995: an improved
      response?
AB  - OBJECTIVES: This study examined whether differences in heat alone, as opposed to
      public health interventions or other factors, accounted for the reduction in heat
      related deaths and paramedic emergency medical service (EMS) runs between 1995
      and 1999 during 2 heat waves occurring in Milwaukee, Wis. METHODS: Two previously
      described prediction models were adapted to compare expected and observed heat
      related morbidity and mortality in 1999 based on the city's 1995 experience.
      RESULTS: Both models showed that heat-related deaths and EMS runs in 1999 were at
      least 49% lower than levels predicted by the 1995 relation between heat and heat
      related deaths or EMS runs. CONCLUSIONS: Reductions in heat-related morbidity and
      mortality in 1999 were not attributable to differences in heat levels alone.
      Changes in public health preparedness and response may also have contributed to
      these reductions.

PMID- 11988456
TI  - Body mass index and disability in adulthood: a 20-year panel study.
AB  - OBJECTIVES: This study examined whether body mass index (BMI) or change in BMI
      raises the risk of disability in adulthood. METHODS: The relation between BMI and
      upper- and lower-body disability was examined among adult subjects from a
      national longitudinal survey (n = 6833). Tobit regression models were used to
      examine the effect of BMI on disability 10 and 20 years later. RESULTS: Obesity
      (BMI > or = 30) at baseline or becoming obese during the study was associated
      with higher levels of upper- and, especially, lower-body disability. In persons
      who began the study with a BMI of 30 or more and became normal weight, disability
      was not reduced. Underweight persons (BMI < 18.5) also manifested higher
      disability in most instances. CONCLUSIONS: Disability risk was higher for obese
      persons, but overweight was not consistently associated with higher disability.

PMID- 11988457
TI  - Trends in mortality due to legal intervention in the United States, 1979 through
      1997.
AB  - OBJECTIVES: This report identifies trends in the number and rate of deaths due to
      law enforcement actions (International Classification of Diseases, Ninth
      Revision, category "legal intervention") in the United States. METHODS: The
      Centers for Disease Control and Prevention's Compressed Mortality File was used
      to determine age-, race-, and sex-specific death rates due to legal intervention
      for the years 1979 through 1997. RESULTS: Males account for nearly all deaths,
      with the death rate for Black males several times that of White males. For both
      Whites and Blacks, the highest rates of death were observed for ages 20 to 34.
      Death rates declined significantly from 1979 to 1988 and remained stable
      thereafter. CONCLUSIONS: While legal intervention is an uncommon cause of death,
      some subpopulations experience rates of death many times that of the US
      population as a whole.

PMID- 11988458
TI  - Overweight status and eating patterns among adolescents: where do youths stand in
      comparison with the healthy people 2010 objectives?
AB  - OBJECTIVES: This study determined the prevalence of Minnesota urban youths
      reaching the Healthy People 2010 objectives for obesity and intake of fat,
      calcium, fruits, vegetables, and grains and compared prevalence rates across
      sociodemographic characteristics. METHODS: The study sample included 4746
      adolescents (aged 11-18 years) from the Minneapolis/St. Paul area who completed
      dietary surveys and participated in anthropometric measurements as part of a
      school-based population study. RESULTS: Considerable gaps were seen between the
      existing prevalence rates for obesity and nutrient and food patterns and the
      targeted Healthy People 2010 prevalence rates. For example, 12.5% of the girls
      and 16.6% of the boys had body mass index values at or greater than the 95th
      percentile (target = 5%). Only 29.5% of the girls and 42.5% of the boys were
      meeting the daily recommended intakes for calcium (target = 75%). Similarly,
      percentages of youths consuming the recommended amounts of fat, fruits,
      vegetables, and grains were lower than the targeted percentages. There were large
      sociodemographic disparities in obesity and eating patterns, particularly across
      race/ethnicity and socioeconomic status. CONCLUSIONS: Concerted public health
      efforts are needed to achieve the Healthy People 2010 objectives for obesity and
      nutrition and to reduce racial/ethnic and socioeconomic disparities.

PMID- 11988459
TI  - Association of medical insurance and other factors with receipt of antiretroviral
      therapy.
AB  - OBJECTIVES: This study was designed to assess sociodemographic and medical
      insurer factors associated with receipt of highly active antiretroviral therapy
      (HAART). METHODS: Patients included (n = 959) were enrolled in the Johns Hopkins
      HIV Clinic after April 1, 1996, received > or = 90 days of care, and had a CD4
      count > or = 500 cells/mm3 or HIV-1 RNA > 20 000 copies/mL. We assessed the
      associations of sociodemographic factors and medical insurance with receipt of
      HAART, stratified by 2 time periods (April 1996 through March 1997 versus April
      1997 through March 1999). RESULTS: HAART was more likely to be used in patients
      who were > 39 years, White, had CD4 counts < 350 cells/mm3, had fewer missed
      clinic visits, and did not have intravenous drug use as their risk factor for HIV
      transmission. In period 1 (April 1996 through March 1997), HAART was more likely
      to be used in patients who were commercially insured than in other payer groups;
      differences between payers narrowed in period 2 (April 1997 through March 1999),
      however, as did differences by race. CONCLUSIONS: Differences in use of HAART on
      the basis of payer have narrowed since 1996. This encouraging finding may
      demonstrate the importance of programs that lower economic barriers to medical
      care.

PMID- 11988461
TI  - My road to biophysics: picking flowers on the way to photosynthesis.

PMID- 11988460
TI  - Effect of birth cohort on risk of hip fracture: age-specific incidence rates in
      the Framingham Study.
AB  - OBJECTIVES: This study examined the effect of birth cohort on incidence rates of
      hip fracture among women and men in the Framingham Study. METHODS: Age-specific
      incidence rates of first hip fracture were presented according to tertile of year
      of birth for 5209 participants of the Framingham Study, a population-based cohort
      followed since 1948. Sex-specific incidence rate ratios were calculated by Cox
      regression to assess the relation between birth cohort and hip fracture
      incidence. RESULTS: An increasing trend in hip fracture incidence rates was
      observed with year of birth for women (trend, P =.05) and men (trend, P =.03).
      Relative to those born from 1887 to 1900 (incidence rate ratio [IRR] = 1.0), age
      specific incidence rates were greatest in the most recent birth cohort, born from
      1911 to 1921 (IRR = 1.4 for women, IRR = 2.0 for men), and intermediate in those
      born from 1901 to 1910 (IRR = 1.2 for women, IRR = 1.5 for men). CONCLUSIONS:
      Results suggest risk of hip fracture is increasing for successive birth cohorts.
      Projections that fail to account for the increase in rates associated with birth
      cohort underestimate the future public health impact of hip fracture in the
      United States.

PMID- 11988462
TI  - The natural history of protein domains.
AB  - Genome sequencing and structural genomics projects are providing new insights
      into the evolutionary history ofprote in domains. As methods for sequence and
      structure comparison improve, more distantly related domains are shown to be
      homologous. Thus there is a need for domain families to be classified within a
      hierarchy similar to Linnaeus' Systema Naturae, the classification of species.
      With such a hierarchy in mind, we discuss the evolution of domains, their
      combination into proteins, and evidence as to the likely origin of protein
      domains. We also discuss when and how analysis of domains can be used to
      understand details of protein function. Unconventional features of domain
      evolution such as intragenomic competition, domain insertion, horizontal gene
      transfer, and convergent evolution are seen as analogs of organismal evolutionary
      events. These parallels illustrate how the concept of domains can be applied to
      provide insights into evolutionary biology.

PMID- 11988463
TI  - Magnetic resonance studies of the bacteriorhodopsin pump cycle.
AB  - Active transport requires the alternation of substrate uptake and release with a
      switch in the access of the substrate binding site to the two sides of the
      membrane. Both the transfer and switch aspects of the photocycle have been
      subjects of magnetic resonance studies in bacteriorhodopsin. The results for ion
      transfer indicate that the Schiff base of the chromophore is hydrogen bonded
      before, during, and after its deprotonation. This suggests that the initial
      complex counterion of the Schiff base decomposes in such a way that the Schiff
      base carries its immediate hydrogen-bonding partner with it as it rotates during
      the first half of the photocycle. If so, bacteriorhodopsin acts as an inward
      directed hydroxide pump rather than as an outward-directed proton pump. The
      studies of the access switch explore both protein-based and chromophore-based
      mechanisms. Combined with evidence from functional studies of mutants and other
      forms of spectroscopy, the results suggest that maintaining access to the
      extracellular side of the protein after photoisomerization involves twisting of
      the chromophore and that the decisive switch in access to the cytoplasmic side
      results from relaxation of the chromophore when the constraints on the Schiff
      base are released by decomposition of the complex counterion.

PMID- 11988464
TI  - Flow cytometric analysis of ligand-receptor interactions and molecular
      assemblies.
AB  - Flow cytometers make homogeneous real-time measurements of ligand-receptor
      interactions and, simultaneously, the physiological responses of cells. Their
      multiparameter capabilities are also useful in resolving multicomponent
      assemblies or in developing multiplexed assays. Recent advances suggest that
      these approaches can be extended in several important ways. Sample delivery in
      the millisecond time domain is applicable to the analysis of complex binding
      kinetics and reaction mechanisms. The homogeneous discrimination of free
      components and particle-based assemblies can be extended into the micromolar
      concentration range. Measurements can be made of molecular assemblies among
      proteins, DNA, RNA, lipids, and carbohydrates on beads. The topography and
      assembly of components within cells can be evaluated with resonance energy
      transfer. Temperature dependence can be evaluated with Peltier temperature
      control. Many assembly endpoints can be assessed through new tools for high
      throughput flow cytometry using plate-based assay formats and small volume
      samples.

PMID- 11988465
TI  - Structural and thermodynamic correlates of T cell signaling.
AB  - The first crystal structures of intact T cell receptors (TCRs) bound to class I
      peptide-MHC (pMHCs) antigens were determined in 1996. Since then, further
      structures of class I TCR/pMHC complexes have explored the degree of structural
      variability in the TCR-pMHC system and the structural basis for positive and
      negative selection. The recent determination of class II and allogeneic class I
      TCR/pMHC structures, as well as those of accessory molecules (e.g., CD3), has
      pushed our knowledge of TCR/pMHC interactions into new realms, shedding light on
      clinical pathologies, such as graft rejection and graft-versus-host disease.
      Furthermore, the determination of coreceptor structures lays the foundation for a
      more comprehensive structural description of the supramolecular TCR signaling
      events and those assemblies that arise in the immunological synapse. While these
      telling photodocumentaries of the TCR/pMHC interaction are composed mainly from
      static crystal structures, a full description of the biological snapshots in T
      cell signaling requires additional analytical methods that record the dynamics of
      the process. To this end, surface plasmon resonance (SPR), isothermal titration
      calorimetry (ITC), and ultracentrifugation (UC) have furnished both affinities
      and kinetics of the TCR/pMHC association. In the past year, structural,
      biochemical, and molecular biological data describing TCR/pMHC interactions have
      sublimely coalesced into a burgeoning well of understanding that promises to
      deliver further insights into T cell recognition. The coming years will, through
      a more intimate union of structural and kinetic data, allow many pressing
      questions to be addressed, such as how TCR/pMHC ligation is affected by
      coreceptor binding and what is the mechanism of TCR signaling in both early and
      late stages of T cell engagement with antigen-presenting cells.

PMID- 11988466
TI  - PIP(2) and proteins: interactions, organization, and information flow.
AB  - We review the physical properties of phosphatidylinositol 4,5-bisphosphate (PIP2)
      that determine both its specific interactions with protein domains of known
      structure and its nonspecific electrostatic sequestration by unstructured
      domains. Several investigators have postulated the existence of distinct pools of
      PIP2 within the cell to account for the myriad functions of this lipid. Recent
      experimental work indicates certain regions of the plasma membrane-membrane
      ruffles and nascent phagosomes-do indeed concentrate PIP2. We consider two
      mechanisms that could account for this phenomenon: local synthesis and
      electrostatic sequestration. We conclude by considering the hypothesis that
      proteins such as MARCKS bind a significant fraction of the PIP2 in a cell,
      helping to sequester it in lateral membrane domains, then release this lipid in
      response to local signals such as an increased concentration of Ca(++)/calmodulin
      or activation of protein kinase C.

PMID- 11988467
TI  - NMR studies of lipoprotein structure.
AB  - Early NMR structural studies of serum lipoproteins were based on (1)H, (13)C,
      (31)P, and (2)H studies of lipid components. From the early studies information
      on composition, lipid chain dynamics and order parameters, and monolayer
      organization resulted. More recently, selective or complete isotopic labeling
      techniques, combined with multidimensional NMR spectroscopy, have resulted in
      structural information of apoprotein fragments. Finally, use of heteronuclear
      three- and four-dimensional experiments have yielded solution structures and
      protein-lipid interactions of intact apolipoproteins C-I, C-II, and A-I.

PMID- 11988468
TI  - The alpha-helix and the organization and gating of channels.
AB  - The structures of an increasing number of channels and other alpha-helical
      membrane proteins have been determined recently, including the KcsA potassium
      channel, the MscL mechanosensitive channel, and the AQP1 and GlpF members of the
      aquaporin family. In this chapter, the orientation and packing characteristics of
      bilayer-spanning helices are surveyed in integral membrane proteins. In the case
      of channels, alpha-helices create the sealed barrier that separates the
      hydrocarbon region of the bilayer from the permeation pathway for solutes. The
      helices surrounding the permeation pathway tend to be rather steeply tilted
      relative to the membrane normal and are consistently arranged in a right-handed
      bundle. The helical framework further provides a supporting scaffold for
      nonmembrane-spanning structures associated with channel selectivity. Although
      structural details remain scarce, the conformational changes associated with
      gating transitions between closed and open states of channels are reviewed,
      emphasizing the potential roles of helix-helix interactions in this process.

PMID- 11988469
TI  - The linkage between protein folding and functional cooperativity: two sides of
      the same coin?
AB  - During the course of their biological function, proteins undergo different types
      of structural rearrangements ranging from local to large-scale conformational
      changes. These changes are usually triggered by their interactions with small
      molecular-weight ligands or other macromolecules. Because binding interactions
      occur at specific sites and involve only a small number of residues, a chain of
      cooperative interactions is necessary for the propagation of binding signals to
      distal locations within the protein structure. This process requires an uneven
      structural distribution of protein stability and cooperativity as revealed by NMR
      detected hydrogen/deuterium exchange experiments under native conditions. The
      distribution of stabilizing interactions does not only provide the architectural
      foundation to the three-dimensional structure of a protein, but it also provides
      the required framework for functional cooperativity. In this review, the
      statistical thermodynamic linkage between protein stability, functional
      cooperativity, and ligand binding is discussed.

PMID- 11988470
TI  - The search and its outcome: high-resolution structures of ribosomal particles
      from mesophilic, thermophilic, and halophilic bacteria at various functional
      states.
AB  - We determined the high-resolution structures of large and small ribosomal
      subunits from mesophilic and thermophilic bacteria and compared them with those
      of the thermophilic ribosome and the halophilic large subunit. We confirmed that
      the elements involved in intersubunit contacts and in substrate binding are
      inherently flexible and that a common ribosomal strategy is to utilize this
      conformational variability for optimizing its functional efficiency and
      minimizing nonproductive interactions. Under close-to-physiological conditions,
      these elements maintain well-ordered characteristic conformations. In unbound
      subunits, the features creating intersubunit bridges within associated ribosomes
      lie on the interface surface, and the features that bind factors and substrates
      reach toward the binding site only when conditions are ripe.

PMID- 11988471
TI  - Principles and biophysical applications of lanthanide-based probes.
AB  - Using luminescent lanthanides, instead of conventional fluorophores, as donor
      molecules in resonance energy transfer measurements offers many technical
      advantages and opens up a wide range of new applications. Advantages include
      farther measurable distances ( approximately 100 A) with greater accuracy,
      insensitivity to incomplete labeling, and the ability to use generic relatively
      large labels, when necessary. Applications highlighted include the study of ion
      channels in living cells, protein-protein interaction in cells, DNA-protein
      complexes, and high-throughput screening assays to measure peptide dimerization
      associated with DNA transcription factors and ligand-receptor interactions.

PMID- 11988472
TI  - Single-particle imaging of macromolecules by cryo-electron microscopy.
AB  - Cryo-electron microscopy (cryo-EM) of biological molecules in single-particle
      (i.e., unordered, nonaggregated) form is a new approach to the study of molecular
      assemblies, which are often too large and flexible to be amenable to X-ray
      crystallography. New insights into biological function on the molecular level are
      expected from cryo-EM applied to the study of such complexes "trapped" at
      different stages of their conformational changes and dynamical interactions.
      Important molecular machines involved in the fundamental processes of
      transcription, mRNA splicing, and translation are examples for successful
      applications of the new technique, combined with structural knowledge gained by
      conventional techniques of structure determination, such as X-ray crystallography
      and NMR.

PMID- 11988473
TI  - Force exertion in fungal infection.
AB  - Fungal pathogens of plants or animals invade their hosts either by secretion of
      lytic enzymes, exerting force, or by a combination of both. Although many fungi
      are thought to rely mostly on lysis of the host tissue, some plant pathogenic
      fungi differentiate complex infection cells that develop enormous turgor
      pressure, which in turn is translated into force used for invasion. In order to
      understand mechanisms of fungal infection in detail, methods have been developed
      that indirectly or directly measure turgor pressure and force. In this article,
      these methods are described and critically discussed, and their importance in
      analysis of fungal infection are outlined.

PMID- 11988474
TI  - The papillomavirus E2 proteins: structure, function, and biology.
AB  - Nearly twenty years after the first high-resolution crystal structures of
      specific protein-DNA complexes were determined, the stereo-chemical basis for
      protein-DNA recognition remains an active area of investigation. One outstanding
      question is, how are proteins able to detect noncontacted sequences in their
      binding sites? The papillomavirus E2 proteins represent a particularly suitable
      group of proteins in which to examine the mechanisms of "indirect readout."
      Coordinated structural and thermodynamic studies of the E2-DNA interaction
      conducted over the past five years are summarized in this review. The data
      support a model in which the electrostatic properties of the individual E2
      proteins correlate with their affinities for intrinsically flexible or rigidly
      prebent DNA targets.

PMID- 11988475
TI  - Conformational dynamics of the chromatin fiber in solution: determinants,
      mechanisms, and functions.
AB  - Chromatin fibers are dynamic macromolecular assemblages that are intimately
      involved in nuclear function. This review focuses on recent advances centered on
      the molecular mechanisms and determinants of chromatin fiber dynamics in
      solution. Major points of emphasis are the functions of the core histone tail
      domains, linker histones, and a new class of proteins that assemble
      supramolecular chromatin structures. The discussion of important structural
      issues is set against a background of possible functional significance.

PMID- 11988476
TI  - Paramagnetic resonance of biological metal centers.
AB  - The review deals with recent advances in magnetic resonance spectroscopy (hf EPR
      and NMR) of paramagnetic metal centers in biological macromolecules. In the first
      half of our chapter, we present an overview of recent technical developments in
      the NMR of paramagnetic bio-macromolecules. These are illustrated by a variety of
      examples deriving mainly from the spectroscopy of metalloproteins and their
      complexes. The second half focuses on recent developments in high-frequency EPR
      spectroscopy and the application of the technique to copper, iron, and manganese
      proteins. Special attention is given to the work on single crystals of copper
      proteins.

PMID- 11988477
TI  - Computational cell biology: spatiotemporal simulation of cellular events.
AB  - The field of computational cell biology has emerged within the past 5 years
      because of the need to apply disciplined computational approaches to build and
      test complex hypotheses on the interacting structural, physical, and chemical
      features that underlie intracellular processes. To meet this need, newly
      developed software tools allow cell biologists and biophysicists to build models
      and generate simulations from them. The construction of general-purpose
      computational approaches is especially challenging if the spatial complexity of
      cellular systems is to be explicitly treated. This review surveys some of the
      existing efforts in this field with special emphasis on a system being developed
      in the authors' laboratory, Virtual Cell. The theories behind both stochastic and
      deterministic simulations are discussed. Examples of respective applications to
      cell biological problems in RNA trafficking and neuronal calcium dynamics are
      provided to illustrate these ideas.

PMID- 11988478
TI  - Rhodopsin: insights from recent structural studies.
AB  - The recent report of the crystal structure of rhodopsin provides insights
      concerning structure-activity relationships in visual pigments and related G
      protein-coupled receptors (GPCRs). The seven transmembrane helices of rhodopsin
      are interrupted or kinked at multiple sites. An extensive network of interhelical
      interactions stabilizes the ground state of the receptor. The ligand-binding
      pocket of rhodopsin is remarkably compact, and several chromophore-protein
      interactions were not predicted from mutagenesis or spectroscopic studies. The
      helix movement model of receptor activation, which likely applies to all GPCRs of
      the rhodopsin family, is supported by several structural elements that suggest
      how light-induced conformational changes in the ligand-binding pocket are
      transmitted to the cytoplasmic surface. The cytoplasmic domain of the receptor
      includes a helical domain extending from the seventh transmembrane segment
      parallel to the bilayer surface. The cytoplasmic surface appears to be
      approximately large enough to bind to the transducin heterotrimer in a one-to-one
      complex. The structural basis for several unique biophysical properties of
      rhodopsin, including its extremely low dark noise level and high quantum
      efficiency, can now be addressed using a combination of structural biology and
      various spectroscopic methods. Future high-resolution structural studies of
      rhodopsin and other GPCRs will form the basis to elucidate the detailed molecular
      mechanism of GPCR-mediated signal transduction.

PMID- 11988479
TI  - Conformational regulation of integrin structure and function.
AB  - Integrins are a structurally elaborate family of heterodimers that mediate
      divalent cation-dependent cell adhesion in a wide range of biological contexts.
      The inserted (I) domain binds ligand in the subset of integrins in which it is
      present. Its structure has been determined in two alternative conformations,
      termed open and closed. In striking similarity to signaling G proteins,
      rearrangement of a Mg(2+)-binding site is linked to large conformational
      movements in distant backbone regions. Mutations have been used to stabilize
      either the closed or open structures. These show that the snapshots of the open
      conformation seen only in the presence of a ligand or a ligand mimetic represent
      a high-affinity, ligand-binding conformation, whereas those of the closed
      conformation correspond to a low-affinity conformation. The C-terminal alpha
      helix moves 10 A down the side of the domain in the open conformation. Locking in
      the conformation of the preceding loop is sufficient to increase affinity for
      ligand 9000-fold. This C-terminal "bell-rope" provides a mechanism for linkage to
      conformational movements in other domains. The transition from the closed to open
      conformation has been implicated in fast (<1 s) regulation of integrin affinity
      in response to activation signals from inside the cell. Recent integrin
      structures and functional studies reveal interactions between beta-propeller, I,
      and I-like domains in the headpiece, and a critical role for integrin EGF domains
      in the stalk region. These studies suggest that the headpiece of the integrin
      faces down toward the membrane in the inactive conformation and extends upward in
      a "switchblade"-like opening motion upon activation. These long-range structural
      rearrangements of the entire integrin molecule involving multiple interdomain
      contacts appear closely linked to conformational changes in the I domain, which
      result in increased affinity and competence for ligand binding.

PMID- 11988480
TI  - Exercise, estrogen, and ischemic cardioprotection by heat shock protein 70.

PMID- 11988481
TI  - Matrix metalloproteinases: are they antiatherogenic but proaneurysmal?

PMID- 11988482
TI  - Heat shock protein 90 in endothelial nitric oxide synthase signaling: following
      the lead(er)?

PMID- 11988483
TI  - "Are we there yet?!" Cardiac channelopathy and our journey toward computational
      medicine.

PMID- 11988484
TI  - CD36 mediates the cardiovascular action of growth hormone-releasing peptides in
      the heart.
AB  - Growth hormone-releasing peptides (GHRPs) are known as potent growth hormone
      secretagogues whose actions are mediated by the ghrelin receptor, a G protein
      coupled receptor cloned from pituitary libraries. Hexarelin, a hexapeptide of the
      GHRP family, has reported cardiovascular activity. To identify the molecular
      target mediating this activity, rat cardiac membranes were labeled with a
      radioactive photoactivatable derivative of hexarelin and purified using lectin
      affinity chromatography and preparative gel electrophoresis. A binding protein of
      M(r) 84 000 was identified. The N-terminal sequence determination of the
      deglycosylated protein was identical to rat CD36, a multifunctional glycoprotein,
      which was expressed in cardiomyocytes and microvascular endothelial cells.
      Activation of CD36 in perfused hearts by hexarelin was shown to elicit an
      increase in coronary perfusion pressure in a dose-dependent manner. This effect
      was lacking in hearts from CD36-null mice and hearts from spontaneous
      hypertensive rats genetically deficient in CD36. The coronary vasoconstrictive
      response correlated with expression of CD36 as assessed by immunoblotting and
      covalent binding with hexarelin. These data suggest that CD36 may mediate the
      coronary vasospasm seen in hypercholesterolemia and atherosclerosis.

PMID- 11988485
TI  - Dual actions of the Galpha(q) agonist Pasteurella multocida toxin to promote
      cardiomyocyte hypertrophy and enhance apoptosis susceptibility.
AB  - Previous attempts to delineate the consequences of Galpha (q) activation in
      cardiomyocytes relied largely on molecular strategies in cultures or transgenic
      mice. Modest levels of wild-type Galpha(q) overexpression induce stable cardiac
      hypertrophy, whereas intense Galpha(q) stimulation induces cardiomyocyte
      apoptosis. The precise mechanism(s) whereby traditional targets of Galpha (q)
      subunits that induce hypertrophy also trigger cardiomyocyte apoptosis is not
      obvious and is explored with recombinant Pasteurella multocida toxin (rPMT, a
      Galpha(q) agonist). Cells cultured with rPMT display cardiomyocyte enlargement,
      sarcomeric organization, and increased atrial natriuretic factor expression in
      association with activation of phospholipase C, novel protein kinase C (PKC)
      isoforms, extracellular signal-regulated protein kinase (ERK), and (to a lesser
      extent) JNK/p38-MAPK. rPMT stimulates the ERK cascade via epidermal growth factor
      (EGF) receptor transactivation in cardiac fibroblasts, but EGF receptor
      transactivation plays no role in ERK activation in cardiomyocytes. Surprisingly,
      rPMT (or novel PKC isoform activation by PMA) decreases basal Akt
      phosphorylation; rPMT prevents Akt phosphorylation by EGF or IGF-1 and
      functionally augments cardiomyocyte apoptosis in response to H2O2. These results
      identify a Galpha(q)-PKC pathway that represses basal Akt phosphorylation and
      impairs Akt stimulation by survival factors. Because inhibition of Akt enhances
      cardiomyocyte susceptibility to apoptosis, this pathway is predicted to
      contribute to the transition from hypertrophy to cardiac decompensation and could
      be targeted for therapy in heart failure.

PMID- 11988486
TI  - Histone acetylation and recruitment of serum responsive factor and CREB-binding
      protein onto SM22 promoter during SM22 gene expression.
AB  - Chromatin acetylation and deacetylation catalyzed by histone acetyltransferases
      (HATs) and histone deacetylases (HDACs) are closely related to eukaryotic gene
      transcription. Although the binding of serum response factor (SRF) to the CArG
      boxes in the promoter region is necessary for SM22 expression, it has never been
      examined whether the local chromatin modification is involved in SM22 gene
      regulation. In this study, we used the SM22 gene as a model to address whether
      transcriptional activation of the gene can be manipulated through adjusting
      histone acetylation of the chromatin template and whether SRF- and HAT-containing
      coactivators can be recruited onto the SM22 promoter region during gene
      activation. Here, we showed that the stimulation of the SM22 promoter by the
      coactivator CREB-binding protein (CBP) was dependent on HAT activity.
      Overexpression of HDACs decreased SM22 promoter activity, whereas trichostatin A,
      an HDAC inhibitor, stimulated SM22 promoter activity in a CArG box-dependent
      manner and induced endogenous SM22 gene expression. Chromatin immunoprecipitation
      assays showed that trichostatin A treatment in 10T1/2 cells induces chromatin
      hyperacetylation in the SM22 gene. Although histone hyperacetylation of the SM22
      gene occurred during SM22 gene expression and SRF and CBP immunocomplexes possess
      HAT activities in smooth muscle cells, both SRF and CBP were recruited to the
      CArG box-containing region of the promoter. This study provides evidence that
      chromatin acetylation is involved in smooth muscle cell-specific gene regulation.

PMID- 11988487
TI  - Domain mapping studies reveal that the M domain of hsp90 serves as a molecular
      scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide
      synthase and NO release.
AB  - Protein-protein interactions with the molecular chaperone hsp90 and
      phosphorylation on serine 1179 by the protein kinase Akt leads to activation of
      endothelial nitric oxide synthase. However, the interplay between these protein
      protein interactions remains to be established. In the present study, we show
      that vascular endothelial growth factor stimulates the coordinated association of
      hsp90, Akt, and resultant phosphorylation of eNOS. Characterization of the
      domains of hsp90 required to bind eNOS, using yeast 2-hybrid, cell-based
      coprecipitation experiments, and GST-fusion proteins, revealed that the M region
      of hsp90 interacts with the amino terminus of eNOS and Akt. The addition of
      purified hsp90 to in vitro kinase assays facilitates Akt-driven phosphorylation
      of recombinant eNOS protein, but not a short peptide encoding the Akt
      phosphorylation site, suggesting that hsp90 may function as a scaffold for eNOS
      and Akt. In vivo, coexpression of adenoviral or the cDNA for hsp90 with eNOS
      promotes nitric oxide release; an effect eliminated using a catalytically
      functional phosphorylation mutant of eNOS. These results demonstrate that
      stimulation of endothelial cells with vascular endothelial growth factor recruits
      eNOS and Akt to an adjacent region on the same domain of hsp90, thereby
      facilitating eNOS phosphorylation and enzyme activation.

PMID- 11988488
TI  - Inhibition of p38 MAPK activation via induction of MKP-1: atrial natriuretic
      peptide reduces TNF-alpha-induced actin polymerization and endothelial
      permeability.
AB  - The atrial natriuretic peptide (ANP) is a cardiovascular hormone possessing
      antiinflammatory potential due to its inhibitory action on the production of
      inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha). The aim
      of this study was to determine whether ANP is able to attenuate inflammatory
      effects of TNF-alpha on target cells. Human umbilical vein endothelial cells
      (HUVECs) were treated with TNF-alpha in the presence or absence of ANP. Changes
      in permeability, cytoskeletal alterations, phosphorylation of p38 MAPK and HSP27,
      and expression of MKP-1 were determined by macromolecule permeability assay,
      fluorescence labeling, RT-PCR, and immunoblotting. Antisense studies were done by
      transfecting cells with MKP-1 antisense oligonucleotides. Activation of HUVECs
      with TNF-alpha lead to a significant increase of macromolecule permeability and
      formation of stress fibers. Treatment of cells with ANP (10(-8) to 10(-6) mol/L)
      significantly reduced the formation of stress fibers and elevated permeability.
      Both TNF-alpha-induced effects were shown to be mediated via the activation of
      p38 using SB203580, a specific inhibitor of p38. ANP significantly reduced the
      TNF-alpha-induced activation of p38 and attenuated the phosphorylation of HSP27,
      a central target downstream of p38. ANP showed no effect on p38 upstream kinases
      MKK3/6. However, a significant induction of the MAPK phosphatase MKP-1 mRNA and
      protein could be observed in ANP-treated cells. Antisense experiments proved a
      causal role for MKP-1 induction in the ANP-mediated inhibition of p38. These data
      show the inhibitory action of ANP on TNF-alpha-induced changes in endothelial
      cytoskeleton and macromolecule permeability involving an MKP-1-induced
      inactivation of p38 MAPK. These effects point to an antiinflammatory and
      antiatherogenic potential of this cardiovascular hormone.

PMID- 11988489
TI  - Expression of slow skeletal troponin I in hearts of phospholamban knockout mice
      alters the relaxant effect of beta-adrenergic stimulation.
AB  - Beta-adrenergic stimulation of the heart results in an enhanced relaxation rate
      in association with phosphorylation of both cardiac troponin I (cTnI) and
      phospholamban (PLB). We studied new lines of mice generated by crossbreeding mice
      that express slow skeletal troponin I (ssTnI) with PLB knockout (PLBKO) mice.
      This crossbreeding resulted in the generation of PLB/cTnI, PLB/ssTnI, PLBKO/cTnI,
      and PLBKO/ssTnI mice. Perfusion with isoproterenol (ISO) significantly increased
      the peak amplitude of fura-2 ratio in PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI
      groups of mice. However, in the presence of ISO, there were no differences in the
      peak amplitude of fura-2 ratio among cells isolated from hearts of PLB/cTnI,
      PLBKO/cTnI, and PLBKO/ssTnI mice. In cells from PLB/cTnI mice, the extent of
      shortening was increased and the time of relaxation was significantly decreased
      during beta-adrenergic stimulation. In PLBKO/cTnI cells, stimulation with ISO
      resulted in an increased extent of shortening and no change in time of
      relaxation. However, stimulation with ISO in cells isolated from PLBKO/ssTnI mice
      not only significantly increased the extent of cell shortening but also increased
      the time of relaxation. We also determined the kinetics of relaxation of
      papillary muscles isolated from all four groups of animals in the presence and
      absence of ISO. Perfusion with ISO increased the rate of relaxation only in
      PLB/cTnI, PLB/ssTnI, and PLBKO/cTnI muscles. During ISO stimulation, the time of
      relaxation was unchanged in PLBKO/ssTnI muscles. Our data directly demonstrate
      that phosphorylation of both PLB and cTnI contributes to increased rate of
      relaxation during beta-adrenergic stimulation.

PMID- 11988490
TI  - Ionic current basis of electrocardiographic waveforms: a model study.
AB  - Body surface electrocardiograms and electrograms recorded from the surfaces of
      the heart are the basis for diagnosis and treatment of cardiac
      electrophysiological disorders and arrhythmias. Given recent advances in
      understanding the molecular mechanisms of arrhythmia, it is important to relate
      these electrocardiographic waveforms to cellular electrophysiological processes.
      This modeling study establishes the following principles: (1) voltage gradients
      created by heterogeneities of the slow-delayed rectifier (I(Ks)) and transient
      outward (I(to)) potassium current inscribe the T wave and J wave, respectively; T
      wave polarity and width are strongly influenced by the degree of intercellular
      coupling through gap-junctions. (2) Changes in [K+]o modulate the T wave through
      their effect on the rapid-delayed rectifier, I(Kr). (3) Alterations of I(Ks),
      I(Kr), and I(Na) (fast sodium current) in long-QT syndrome (LQT1, LQT2, and LQT3,
      respectively) are reflected in characteristic QT-interval and T-wave changes;
      LQT1 prolongs QT without widening the T wave. (4) Accelerated inactivation of
      I(Na) on the background of large epicardial I(to) results in ST elevation
      (Brugada phenotype) that reflects the degree of severity. (5) Activation of the
      ATP-sensitive potassium current, I(K(ATP)), is sufficient to cause ST elevation
      during acute ischemia. These principles provide a mechanistic cellular basis for
      interpretation of electrocardiographic waveforms.

PMID- 11988491
TI  - Reduced atherosclerotic plaque but enhanced aneurysm formation in mice with
      inactivation of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene.
AB  - Development and progression of atherosclerotic lesions and aneurysm formation
      were investigated in mice with single or combined deficiency of apolipoprotein E
      (ApoE) and tissue inhibitor of metalloproteinase-1 (TIMP-1) kept on a cholesterol
      rich diet for 30 weeks. Atherosclerotic lesions throughout the thoracic aorta
      were significantly (P<0.001) larger in mice wild-type for TIMP-1 (ApoE-/-:TIMP
      1+/+) than in mice deficient in TIMP-1 (ApoE-/-:TIMP-1-/-). Aneurysms in the
      thoracic and abdominal aortas were less frequent in ApoE-/-:TIMP-1+/+ mice than
      in ApoE-/-:TIMP-1-/- mice (11+/-3.0 versus 23+/-5.1 aneurysms per 100 sections
      analyzed, mean+/-SD, P<0.001). Immunocytochemistry revealed enhanced accumulation
      of Oil red O-stained lipids, colocalizing with macrophages in atherosclerotic
      lesions of ApoE-/-:TIMP-1-/- mice (P<0.05). In situ zymography using a casein
      substrate showed enhanced lysis in plaques of ApoE-/-:TIMP-1-/- mice as compared
      with ApoE-/-:TIMP-1+/+ mice (P<0.01). MMP activity was most pronounced at sites
      where degradation of the elastic lamina occurred. These data suggest that
      enhanced MMP activity, as a result of TIMP-1 deficiency, contributes to a
      reduction of atherosclerotic plaque size but promotes aneurysm formation.

PMID- 11988492
TI  - Functional reconstitution of endothelial nitric oxide synthase reveals the
      importance of serine 1179 in endothelium-dependent vasomotion.
AB  - Phosphorylation of endothelial nitric oxide synthase (eNOS) at serine 1179 can
      activate the enzyme, leading to NO release. Because eNOS is important in
      regulating vascular tone, we investigated whether phosphorylation of this residue
      is involved in vasomotion. Adenoviral transduction of endothelial cells (ECs)
      with the phosphomimetic S1179DeNOS markedly increased basal and vascular
      endothelial cell growth factor (VEGF)-stimulated NO release compared with cells
      transduced with wild-type virus. Conversely, adenoviral transduction of ECs with
      the non-phosphorylatable S1179AeNOS suppressed basal and stimulated NO release.
      Using a novel method for luminal delivery of adenovirus, transduction of the
      endothelium of carotid arteries from eNOS knockout mice with S1179DeNOS
      completely restored NO-mediated dilatation to acetylcholine (ACh), whereas
      vasomotor responses in arteries transduced with S1179AeNOS were significantly
      attenuated. Basal NO release was also significantly reduced in arteries
      transduced with S1179AeNOS, compared with S1179DeNOS. Thus, our data directly
      demonstrate that phosphorylation of eNOS at serine 1179 is an important regulator
      of basal and stimulated NO release in ECs and in intact blood vessels.

PMID- 11988493
TI  - Exercise improves postischemic cardiac function in males but not females:
      consequences of a novel sex-specific heat shock protein 70 response.
AB  - Exercise is a physiological inducer of the cardioprotective heat shock protein,
      Hsp70. The putative biological events involved in signaling this response exhibit
      sexual dimorphism. Thus, it was hypothesized that exercise-mediated induction of
      Hsp70 would demonstrate sex specificity. After treadmill running, male rats
      exhibited 2-fold greater levels of cardiac Hsp70 relative to the levels in
      gonadally intact female rats (P<0.001). Ovariectomized female rats exhibited
      exercise-mediated induction of Hsp70 similar to that observed for male rats, and
      estrogen treatment in these female rats reversed this effect (P<0.001).
      Attenuation of Hsp70 signaling by estrogen was non-receptor-mediated, possibly
      involving a cellular membrane-stabilizing mechanism of action. The physiological
      importance of this sex-specific hormone-mediated stress response is underscored
      by the disparity in functional adaptation in response to exercise between male
      rats and female rats. Exercise markedly improved postischemic left ventricular
      developed pressure, the maximal rate of contraction, and maximal rate of
      relaxation, and it reduced left ventricular end-diastolic pressure in male rats
      (P<0.001). No such benefit of exercise was observed in intact female rats. A
      causal role for Hsp70 in this sex-specific cardioprotective adaptation was
      indicated, inasmuch as ablation of Hsp70 induction with antisense
      oligonucleotides designed against Hsp70 transcripts attenuated improvement in the
      recovery of cardiac function in exercised male rats (P<0.05). Thus, the sex
      specific hormone-mediated Hsp70 response to exercise results in cardioprotective
      adaptation, preferentially in male rats relative to female rats. These findings
      suggest that exercise may be more important for males than for females in
      defending against the effects of heart disease and offer a novel manner by which
      males may reduce the sex gap in susceptibility to adverse cardiac events.

PMID- 11988494
TI  - Wall tissue remodeling regulates longitudinal tension in arteries.
AB  - Changes in blood pressure or flow induce arterial remodeling that normalizes
      mechanical loads that are imposed on arterial tissue. Arteries are also under
      substantial longitudinal stretch (axial strain) that may be altered by growth or
      atrophy of tissues to which they are attached. We therefore tested whether axial
      strain is also regulated in a negative feedback manner through arterial
      remodeling. Axial strain in rabbit carotid arteries was increased from 62+/-2% to
      97+/-2% without altering other mechanical loads on wall tissues. Strain was
      reduced within 3 days and completely normalized by 7 days. Remodeling involved
      tissue elaboration, endothelial cell replication rates were increased by >50-fold
      and smooth muscle cell replication rates were increased by >15-fold, and
      substantially elevated DNA, elastin, and collagen contents were recorded. Also,
      increased rates of apoptosis were indicated by degradation of DNA into
      oligonucleosomes, and matrix remodeling was reflected in enlarged fenestrae in
      the internal elastic lamina and increased expression and activation of
      gelatinases, especially matrix metalloproteinase-2. Intriguingly, reduced axial
      strain was not normalized, presumably because remodeling processes, apart from
      cell contraction, are ineffective in decreasing strain, and arterial smooth
      muscle orientation precludes large effects of contraction on axial strain.

PMID- 11988495
TI  - Locus for elevated apolipoprotein B levels on chromosome 1p31 in families with
      familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCH), a common cause of premature coronary
      artery disease, is genetically complex and poorly understood. Recently, a major
      locus on chromosome 1q21-23 exhibiting highly significant linkage was identified
      in Finnish FCH families by use of a parametric analysis. We now report highly
      significant evidence of linkage (maximum LOD score 3.8, recombination fraction 0)
      of an important FCH phenotype, elevated apolipoprotein B (apoB) levels, to a
      distinctly separate locus on chromosome 1p31 in Dutch pedigrees. ApoB is the
      major protein on very low density and low density lipoproteins, and elevated apoB
      levels have been used as a surrogate trait for FCH. Additional microsatellite
      markers in the 1p31 region were genotyped, and evidence of linkage improved
      (maximum LOD score 4.7) in a multipoint analysis of two markers in the peak
      region. The leptin receptor gene resides within this locus and is involved in
      obesity and insulin/glucose homeostasis. However, there was no evidence of an
      association between leptin receptor and apoB levels, raising the possibility that
      another gene on this chromosomal region contributes to elevated apoB levels in
      this Dutch population. This is one of the first loci identified for apoB levels
      in humans and is the second major locus implicated in the genetic etiology of
      FCH.

PMID- 11988496
TI  - Guided tissue regeneration of vascular grafts in the peritoneal cavity.

PMID- 11988497
TI  - LacZ-promoter fusions: the effect of growth.

PMID- 11988498
TI  - The genomes of Pseudomonas encode a third HU protein.

PMID- 11988499
TI  - The fate of microbial mutators.

PMID- 11988500
TI  - Fine-scale genetic analyses reveal unexpected spatial-temporal heterogeneity in
      two natural populations of the commercial mushroom Agaricus bisporus.
AB  - This study examined the fine-scale genetic variation of the commercial mushroom,
      Agaricus bisporus, over 2 years at two sites in France. One site was a meadow
      fertilized with horse manure and disturbed regularly by humans; the other was a
      Monterey cypress forest free of human disturbance. Altogether, 50 mushrooms were
      collected and analysed for mitochondrial and nuclear genetic variation marked by
      RFLPs and multilocus enzyme electrophoretic polymorphisms. Population samples
      from these two sites were genetically different and both sites contained high
      levels of genetic diversity. No identical genotypes were found at either site
      between the 2 years and there was little evidence for extensive vegetative
      clonality for this species. Contrary to expectations, very limited evidence of
      pseudohomothallic reproduction was found. Results from tests of Hardy-Weinberg
      equilibrium and genotypic equilibrium showed that outcrossing and recombination
      have played significant roles in both populations. The results demonstrated
      spatial-temporal genetic heterogeneity of A. bisporus in natural populations.

PMID- 11988501
TI  - Production of a monoclonal antibody specific to the genus Trichoderma and closely
      related fungi, and its use to detect Trichoderma spp. in naturally infested
      composts.
AB  - Studies of the interactions between hyperparasitic fungi and their hosts are
      severely hampered by the absence of methods that allow the unambiguous
      identification of individual genera in complex environments that contain mixed
      populations of fungi, such as soil or compost. This study details the development
      of a monoclonal antibody (MF2) that allows the detection and recovery of
      Trichoderma spp. in naturally infested composts, and the visualization of
      hyperparasitic strains of Trichoderma during antagonistic interactions with their
      hosts. Murine monoclonal antibody MF2, of immunoglobulin class M (IgM), was
      raised against a protein epitope of a glycoprotein antigen(s) specific for
      species of the genus Trichoderma and for the closely related fungi Gliocladium
      viride, Hypomyces chrysospermus, Sphaerostilbella spp. and Hypocrea spp. MF2 did
      not react with antigens from Gliocladium catenulatum, Gliocladium roseum, Nectria
      ochroleuca and Clonostachys spp., nor with a range of unrelated soil- and compost
      borne fungi. Extracellular production of the MF2 antigen was constitutive.
      Western-blotting analysis showed that MF2 bound to a ladder of proteins with
      apparent molecular masses in the range 35-200 kDa. Immunofluorescence studies
      showed that MF2 bound strongly to the cell walls of hyphae and phialides and the
      intercalary and terminal chlamydospores of Trichoderma spp., whereas immunogold
      electron microscopy revealed strong binding of MF2 to the cell walls and septa of
      hyphae and to the cell walls of phialoconidia. In immunofluorescence studies of
      dual cultures of Trichoderma and Rhizoctonia solani, only the cell walls of the
      hyperparasite, which coiled around the host, were stained by MF2. The specificity
      of MF2 enabled the development of a combined baiting-ELISA technique for the
      detection of Trichoderma spp. in naturally infested composts. The specificity of
      this technique was confirmed by phylogenetic analysis based on sequences of the
      ITS1-5.8S-ITS2 rRNA-encoding regions of the isolates.

PMID- 11988502
TI  - Disruption in Candida albicans of the TPS2 gene encoding trehalose-6-phosphate
      phosphatase affects cell integrity and decreases infectivity.
AB  - The gene CaTPS2 encoding trehalose-6-phosphate (T6P) phosphatase from Candida
      albicans has been cloned and disrupted in this organism. The Catps2/Catps2 mutant
      did not accumulate trehalose but accumulated high levels of T6P. Disruption of
      the two copies of the CaTPS2 gene did not abolish growth even at 42 degrees C,
      but decreased the growth rate. In the stationary phase, the Catps2/Catps2 mutant
      aggregated, more than 50% of its cells became permeable to propidium iodide and a
      large amount of protein was found in the culture medium. Aggregation occurred
      only at pH values higher than 7 and was avoided by osmoprotectants; it was never
      observed during the exponential phase of growth. The mutant formed colonies with
      a smooth border on Spider medium. Mice inoculated with 1.5 x 10(6) c.f.u. of wild
      type cells died after 8 days, while 80% of those inoculated with the same number
      of c.f.u. of the Catps2/Catps2 mutant survived for at least 1 month.
      Reintroduction of the wild-type CaTPS2 gene in the Catps2/Catps2 mutant abolished
      the phenotypes described. It is hypothesized that the accumulation of T6P
      interferes with the assembly of a normal cell wall.

PMID- 11988503
TI  - The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase:
      evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient
      mutants.
AB  - The enzyme 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase catalyses
      the first step in aromatic amino acid biosynthesis in prokaryotes, plants and
      fungi. Cells of Saccharomyces cerevisiae contain two catalytically redundant DAHP
      synthases, encoded by the genes ARO3 and ARO4, whose activities are feedback
      inhibited by phenylalanine and tyrosine, respectively. ARO3/4 gene transcription
      is controlled by GCN4. The authors previously cloned an ARO3 gene orthologue from
      Candida albicans and found that: (1) it can complement an aro3 aro4 double
      mutation in S. cerevisiae, an effect inhibited by excess phenylalanine, and (2) a
      homozygous aro3-deletion mutant of C. albicans is phenotypically Aro(+),
      suggesting the existence of another isozyme(s). They now report the
      identification and functional characterization of the C. albicans orthologue of
      S. cerevisiae Aro4p. The two Aro4p enzymes share 68% amino acid identity.
      Phylogenetic analysis places the fungal DAHP synthases in a cluster separate from
      prokaryotic orthologues and suggests that ARO3 and ARO4 arose from a single gene
      via a gene duplication event early in fungal evolution. C. albicans ARO4 mRNA is
      elevated upon amino acid starvation, consistent with the presence of three
      putative Gcn4p-responsive elements (GCREs) in the gene promoter sequence. C.
      albicans ARO4 complements an aro3 aro4 double mutation in S. cerevisiae, an
      effect inhibited by excess tyrosine. The authors engineered Deltaaro3/Deltaaro3
      Deltaaro4/MET3p::ARO4 cells of C. albicans (with one wild-type copy of ARO4
      placed under control of the repressible MET3 promoter) and found that they fail
      to grow in the absence of aromatic amino acids when ARO4 expression is repressed,
      and that this growth defect can be partially rescued by aromatic amino acids and
      certain aromatic amino acid pathway intermediates. It is concluded that, like S.
      cerevisiae, C. albicans contains two DAHP synthases required for the first step
      in the aromatic amino acid biosynthetic pathway.

PMID- 11988504
TI  - Aspartyl protease from Trichoderma harzianum CECT 2413: cloning and
      characterization.
AB  - A gene that encodes an extracellular aspartyl protease from Trichoderma harzianum
      CECT 2413, papA, has been isolated and characterized. Based on several conserved
      regions of other fungal acid proteases, primers were designed to amplify a probe
      that was used to isolate the papA gene from a genomic library of T. harzianum.
      papA was an intronless ORF which encoded a polypeptide of 404 aa, including a
      prepropeptide at the N-terminal region formed by one putative signal peptide, a
      second peptide which could be cleaved to activate the enzyme and the active
      protease of calculated 36.7 kDa and pI 4.35. Northern experiments indicated that
      papA gene was pH regulated, repressed by ammonium, glucose and glycerol, and
      induced by organic nitrogen sources. The promoter possessed potential AreA, PacC
      and MYC sites for nitrogen, pH and mycoparasitism regulation respectively, but
      lacked potential CreA sites for carbon regulation. IEF and zymograms indicated
      that PAPA was a pepstatin-sensitive aspartyl protease of pI 4.5. Transformants
      from T. harzianum CECT 2413 cultivated in yeast extract-supplemented medium
      overexpressed papA and had a fourfold increase in protease activity compared to
      the wild-type, while transformants that overexpressed the beta-1,6-glucanase gene
      bgn16.2 and papA had an additional 30% increase in beta-1,6-glucanase activity
      compared to bgn16.2 single transformants. Overexpression of both genes in
      ammonium-supplemented medium did not result in higher levels of PAPA and/or
      BGN16.2 proteins. These results indicated that both PAPA and beta-1,6-glucanase
      undergo proteolysis in ammonium-supplemented medium but PAPA is not responsible
      for beta-1,6-glucanase degradation.

PMID- 11988505
TI  - Mutational analysis of K28 preprotoxin processing in the yeast Saccharomyces
      cerevisiae.
AB  - K28 killer strains of Saccharomyces cerevisiae are permanently infected with a
      cytoplasmic persisting dsRNA virus encoding a secreted alpha/beta heterodimeric
      protein toxin that kills sensitive cells by cell-cycle arrest and inhibition of
      DNA synthesis. In vivo processing of the 345 aa toxin precursor (preprotoxin;
      pptox) involves multiple internal and carboxy-terminal cleavage events by the
      prohormone convertases Kex2p and Kex1p. By site-directed mutagenesis of the
      preprotoxin gene and phenotypic analysis of its in vivo effects it is now
      demonstrated that secretion of a biological active virus toxin requires signal
      peptidase cleavage after Gly(36) and Kex2p-mediated processing at the alpha
      subunit N terminus (after Glu-Arg(49)), the alpha subunit C terminus (after Ser
      Arg(149)) and at the beta subunit N terminus (after Lys-Arg(245)). The mature C
      terminus of the beta subunit is trimmed by Kex1p, which removes the terminal
      Arg(345) residue, thus uncovering the toxin's endoplasmic reticulum targeting
      signal (HDEL) which--in a sensitive target cell--is essential for retrograde
      toxin transport. Interestingly, both toxin subunits are covalently linked by a
      single disulfide bond between alpha-Cys(56) and beta-Cys(340), and expression of
      a mutant toxin in which beta-Cys(340) had been replaced by Ser(340) resulted in
      the secretion of a non-toxic alpha/beta heterodimer that is blocked in retrograde
      transport and incapable of entering the yeast cell cytosol, indicating that one
      important in vivo function of beta-Cys(340) might be to ensure accessibility of
      the toxin's beta subunit C terminus to the HDEL receptor of the target cell.

PMID- 11988506
TI  - Transglutaminase activity is involved in Saccharomyces cerevisiae wall
      construction.
AB  - Transglutaminase activity, which forms the interpeptidic cross-link N(epsilon)
      (gamma-glutamyl)-lysine, was demonstrated in cell-free extracts of Saccharomyces
      cerevisiae by incorporation of [(14)C]lysine into an exogenous acceptor, N,N'
      dimethylcasein. Higher levels of the activity were present in the cell wall,
      which also contained endogenous acceptors. The enzyme activity in the wall was
      inhibited by cystamine, a known inhibitor of transglutaminase, and by EDTA,
      indicating a cation-dependent activity. After the endogenous wall acceptors were
      labelled radioactively by transglutaminase, extraction with SDS solubilized about
      50% of the total radioactivity, while Zymolyase and chitinase each released a
      further 3%. The proteins solubilized by SDS had molecular masses less than 50
      kDa, whereas the material released by Zymolyase or chitinase had molecular masses
      greater than 180 kDa, suggesting a precursor-product relationship. Cystamine
      inhibited the growth of several strains of S. cerevisiae. Treated cells showed
      increased sensitivity to Zymolyase and appeared as protoplasts, indicating gross
      alterations in the cell wall. These data suggest that transglutaminase may be
      involved in the formation of covalent cross-links between wall proteins during
      wall construction.

PMID- 11988507
TI  - Repression of chsB expression reveals the functional importance of class IV
      chitin synthase gene chsD in hyphal growth and conidiation of Aspergillus
      nidulans.
AB  - The functions of two previously identified chitin synthase genes in Aspergillus
      nidulans, chsB and chsD, were analysed. First, a conditional chsB mutant was
      constructed in which the expression of chsB is under the control of a repressible
      promoter, the alcA promoter, of A. nidulans. Under repressing conditions, the
      mutant grew slowly and produced highly branched hyphae, supporting the idea that
      chsB is involved in normal hyphal growth. The involvement of chsB in conidiation
      was also demonstrated. Next, double mutants of chsB and chsD were constructed, in
      which chsB was placed under the control of the alcA promoter and chsD was
      replaced with the argB gene of A. nidulans. These double mutants grew more slowly
      than the chsB single mutant under high-osmolarity conditions. The hyphae of the
      double mutant appeared to be more disorganized than those of the chsB single
      mutant. It was also found that ChsD was functionally implicated in conidiation
      when the expression of chsB was limited. These results indicate the importance of
      the ChsD function in the absence of chsB expression. The roles of ChsB and ChsD
      in hyphal growth and in conidiation were supported by the analysis of the spatial
      expression patterns of chsB and chsD, using lacZ of Escherichia coli as a
      reporter gene.

PMID- 11988508
TI  - The "primitive" microaerophile Giardia intestinalis (syn. lamblia, duodenalis)
      has specialized membranes with electron transport and membrane-potential
      generating functions.
AB  - Here it is shown that the flagellated protozoon Giardia intestinalis, commonly
      regarded as an early branching eukaryote because of its lack of mitochondria, has
      membraneous structures that partition the cationic, membrane-potential-sensitive
      fluorophore rhodamine 123. This organism also reduces a tetrazolium fluorogen at
      discrete plasma-membrane-associated sites. That these functions occur in
      distinctive specialized membrane systems supports the growing evidence that G.
      intestinalis may not be primitive, but is derived from an aerobic, mitochondria
      containing flagellate.

PMID- 11988509
TI  - Enteropathogenic Escherichia coli translocate Tir and form an intimin-Tir
      intimate attachment to red blood cell membranes.
AB  - Type III secretion allows bacteria to inject effector proteins into host cells.
      In enteropathogenic Escherichia coli (EPEC) the type III secreted protein, Tir,
      is translocated to the host-cell plasma membrane where it functions as a receptor
      for the bacterial adhesin intimin, leading to intimate bacterial attachment and
      "attaching and effacing" (A/E) lesion formation. To study EPEC type III secretion
      the interaction of EPEC with monolayers of red blood cells (RBCs) has been
      exploited and in a recent study [Shaw, R. K., Daniell, S., Ebel, F., Frankel, G.
      & Knutton, S. (2001 ). Cell Microbiol 3, 213-222] it was shown that EPEC induced
      haemolysis of RBCs and translocation of EspD, a putative pore-forming type III
      secreted protein in the RBC membrane. Here it is demonstrated that EPEC are able
      to translocate and correctly insert Tir into the RBC membrane and produce an
      intimin-Tir intimate bacterial attachment, identical to that seen in A/E lesions.
      Following translocation Tir did not undergo any change in apparent molecular mass
      or become tyrosine-phosphorylated and there was no focusing of RBC cytoskeletal
      actin beneath intimately adherent bacteria, and no pedestal formation. This
      study, employing an RBC model of infection, has demonstrated that Tir
      translocation can be separated from host-cell-mediated Tir modifications; the
      data show that the EPEC type III protein translocation apparatus is sufficient to
      deliver and correctly insert Tir into host-cell membranes independent of
      eukaryotic cell functions.

PMID- 11988511
TI  - Direct quantitative differentiation between Prevotella intermedia and Prevotella
      nigrescens in clinical specimens.
AB  - This paper describes a quantitative fluorescent in situ hybridization (FISH)
      assay for the differential identification of Prevotella intermedia and Prevotella
      nigrescens in clinical samples, and compares its performance with less
      discriminatory culture and quantitative immunofluorescence (IF) assays.
      Fluorescence-labelled oligonucleotide probes directed to specific 16S rRNA
      sequences of P. intermedia, P. nigrescens, Prevotella pallens and Prevotella
      denticola were hybridized under stringent conditions with cultured reference
      strains or plaque samples from deep periodontal pockets. Probe specificity was
      defined with strains from multiple oral Prevotella species. The lower detection
      level of the assays was approximately 3x10(3) target cells per ml of plaque
      sample suspension. P. intermedia, P. nigrescens, P. pallens and P. denticola were
      detected in plaques with prevalences of 69, 67, 0 and 28%, respectively. On
      average, 3.9 x 10(6) P. intermedia, 3.1 x 10(6) P. nigrescens and 5.6 x 10(5) P.
      denticola cells were counted per positive sample. All three species were found
      almost exclusively in dense mixed aggregates. Quantitative FISH data agreed
      satisfactorily with corresponding IF data (r=0.711). Both FISH and IF
      enumerations of the sum of P. intermedia and P. nigrescens markedly exceeded the
      c.f.u. counts of black-pigmented colonies in Porphyromonas gingivalis-free
      cultured subgingival plaques. The results demonstrate the validity of this new
      assay. Unlike established IF, culture, PCR or checkerboard DNA hybridization
      assays, this FISH assay differentiates quantitatively between P. intermedia and
      P. nigrescens, provides visual accuracy control, and offers insights into the
      spatial distribution of the target cells within a clinical sample.

PMID- 11988512
TI  - Evidence of intermolecular recombination between extrachromosomal DNAs in
      phytoplasma: a trigger for the biological diversity of phytoplasma?
AB  - Recombination among bacterial extrachromosomal DNAs (EC-DNAs) plays a major
      evolutionary role by creating genetic diversity, and provides the potential for
      rapid adaptation to new environmental conditions. Previously, a 7 kbp EC-DNA,
      EcOYW1, with a geminivirus-like rolling-circle-replication protein (Rep) gene was
      isolated and characterized from an original wild-type line (OY-W) of onion
      yellows (OY) phytoplasma, an endocellular cell-wall-less prokaryote that inhabits
      the cytoplasm of both plant and insect cells. EcOYW1, found in OY-W, was not
      present in a mild-symptom line (OY-M) derived from OY-W. A 4 kbp EC-DNA, pOYW,
      was also isolated and characterized from OY-W, and its pLS1-plasmid-like rep gene
      was expressed. This paper describes the isolation and sequencing of an EC-DNA of
      5560 nt, EcOYW2, from OY-W, and its counterpart EC-DNA of 5025 nt, EcOYM, from OY
      M. EcOYW2 and EcOYM contained seven and six ORFs, respectively. They both encoded
      a geminivirus-like Rep and a putative single-stranded-DNA-binding protein (SSB).
      Southern blot analysis indicated that no more EC-DNAs with a rep gene exist in
      either OY-W or OY-M, which means that the complete set of EC-DNAs has been cloned
      from the OY-W and OY-M lines of OY phytoplasmas. Sequence analysis revealed that
      both EcOYW2 and EcOYM have chimeric structures of previously characterized EcOYW1
      and pOYW, suggesting that they have a recombinational origin. This is the first
      evidence of intermolecular recombination between EC-DNAs in phytoplasma. The
      possible implications of these findings in increasing the biological diversity of
      phytoplasma are discussed.

PMID- 11988513
TI  - Identification of novel sulfur-containing bacterial polyesters: biosynthesis of
      poly(3-hydroxy-S-propyl-omega-thioalkanoates) containing thioether linkages in
      the side chains.
AB  - This study describes the biosynthesis of novel sulfur-containing
      polyhydroxyalkanoates (PHAs), which consist exclusively of
      hydroxypropylthioalkanoic acid containing thioether groups in the side chains. In
      addition, the utilization of alkylthioalkanoic acids (=thia fatty acids) by
      various bacteria was investigated. Based on feedings with propylthiooctanoic acid
      (PTO) or propylthiohexanoic acid, the metabolically engineered PHA-negative
      mutant PHB(-)4 of Ralstonia eutropha, which harbours plasmid pBBR1::phaC1
      expressing the PHA synthase of Pseudomonas mendocina, synthesized two novel
      poly(3-hydroxy-S-propyl-omega-thioalkanoic) acids [poly(3HPTA)s]. A terpolyester
      consisting of 3-hydroxypropylthiobutyric acid (3HPTB), 3
      hydroxypropylthiohexanoic acid (3HPTHx) and 3-hydroxypropyl- thiooctanoic acid
      (3HPTO) was synthesized from PTO, whereas a co-polyester of 3HPTB and 3HPTHx was
      synthesized from propylthiohexanoic acid. Fed-batch fermentation of R. eutropha
      PHB(-)4(pBBR1::phaC1) on PTO was done on a 26-litre scale, providing a cell
      density of 7.3 g l(-1), from which 45 g of the novel poly(3HPTB-co-3HPTHx-co
      3HPTO) were isolated. The chemical structures of the poly(3HPTA)s were identified
      by gas chromatography/mass spectrometry, elemental sulfur analysis, partial
      pyrolysis and detailed mass spectrometric analysis, exhibiting 3HPTB, 3HPTHx and
      3HPTO as constituents. These novel, hitherto undescribed, constituents of PHAs
      were randomly distributed in the co-polyesters.

PMID- 11988510
TI  - Sample sequencing of a selected region of the genome of Erwinia carotovora subsp.
      atroseptica reveals candidate phytopathogenicity genes and allows comparison with
      Escherichia coli.
AB  - Genome sequencing is making a profound impact on microbiology. Currently,
      however, only one plant pathogen genome sequence is publicly available and no
      genome-sequencing project has been initiated for any species of the genus
      Erwinia, which includes several important plant pathogens. This paper describes a
      targeted sample sequencing approach to study the genome of Erwinia carotovora
      subsp. atroseptica (Eca), a major soft-rot pathogen of potato. A large insert DNA
      (approx. 115 kb) library of Eca was constructed using a bacterial artificial
      chromosome (BAC) vector. Hybridization and end-sequence data revealed two
      overlapping BAC clones that span an entire hrp gene cluster. Random subcloning
      and one-fold sequence coverage (>200 kb) across these BACs identified 25 (89%) of
      28 hrp genes predicted from the orthologous hrp cluster of Erwinia amylovora.
      Regions flanking the hrp cluster contained orthologues of known or putative
      pathogenicity operons from other Erwinia species, including dspEF (E. amylovora),
      hecAB and pecSM (E. chrysanthemi), sequences similar to genes from the plant
      pathogen Xylella fastidiosa, including haemagglutinin-like genes, and sequences
      similar to genes involved in rhizobacterium-plant interactions. Approximately 10%
      of the sequences showed strongest nucleotide similarities to genes in the closely
      related model bacterium and animal pathogen Escherichia coli. However, the
      positions of some of these genes were different in the two genomes. Approximately
      30% of sequences showed no significant similarity to any database entries. A
      physical map was made across the genomic region spanning the hrp cluster by
      hybridization to the BAC library and to digested BAC clones, and by PCR between
      sequence contigs. A multiple genome coverage BAC library and one-fold sample
      sequencing are an effective combination for extracting useful information from
      important regions of the Eca genome, providing a wealth of candidate novel
      pathogenicity genes for functional analyses. Other genomic regions could be
      similarly targeted.

PMID- 11988514
TI  - Identification of phenyldecanoic acid as a constituent of triacylglycerols and
      wax ester produced by Rhodococcus opacus PD630.
AB  - Phenyldecane supported growth and lipid accumulation of Rhodococcus opacus PD630
      during cultivation under nitrogen-limiting conditions. The results of this study
      suggested that the hydrocarbon phenyldecane was degraded by monoterminal
      oxidation, followed by beta-oxidation of the alkyl side-chain to phenylacetic
      acid, and by an additional degradative route for the oxidation of the latter to
      intermediates of the central metabolism. alpha-Oxidation of phenyldecanoic acid
      also occurred to some extent. Phenyldecanoic acid, the monoterminal oxidation
      product, was also utilized for the biosynthesis of a novel wax ester and novel
      triacylglycerols. The formation of the wax ester phenyldecylphenyldecanoate
      probably resulted from the condensation of phenyldecanoic acid and phenyldecanol,
      which were produced as metabolites during the catabolism of phenyldecane. Two
      types of triacylglycerol were detected in phenyldecane-grown cells of strain
      PD630. Triacylglycerols containing only odd- and even-numbered aliphatic fatty
      acids, as well as triacylglycerols in which one fatty acid was replaced by a
      phenyldecanoic acid residue, occurred. Other phenyl intermediates, such as
      phenylacetic acid, phenylpropionic acid, 4-hydroxyphenylpropionic acid,
      protocatechuate and homogentisic acid, were excreted into the medium during
      cultivation on phenyldecane. On the basis of the results obtained, pathways for
      the catabolism and assimilation of phenyldecane by R. opacus PD630 are discussed.

PMID- 11988515
TI  - Characterization of the hom-thrC-thrB cluster in aminoethoxyvinylglycine
      producing Streptomyces sp. NRRL 5331.
AB  - Three genes from the aminoethoxyvinylglycine (AVG)-producing Streptomyces sp.
      NRRL 5331 involved in threonine biosynthesis, hom, thrB and thrC, encoding
      homoserine dehydrogenase (HDH), homoserine kinase (HK) and threonine synthase
      (TS), respectively, have been cloned and sequenced. The hom and thrC genes appear
      to be organized in a bicistronic operon as deduced by disruption experiments. The
      thrB gene, however, is transcribed as a monocistronic transcript. The encoded
      proteins are quite similar to the HDH, HK and TS proteins from other bacterial
      species. The overall organization of these three genes, in the order hom-thrC
      thrB, differs from that in other bacteria and is similar to that reported in the
      Streptomyces coelicolor genome sequence. This is the first time in which the gene
      cluster for the three last steps of threonine biosynthesis has been characterized
      from a streptomycete. Disruption of thrC indicated that threonine is not a direct
      precursor for AVG biosynthesis in Streptomyces sp. NRRL 5331 and suggested that
      the branching point of the aspartic acid-derived biosynthetic route of this
      metabolite should lie earlier on the threonine biosynthetic route.

PMID- 11988516
TI  - cDNA cloning confirms the polyadenylation of RNA decay intermediates in
      Streptomyces coelicolor.
AB  - In Escherichia coli the poly(A) tails of messenger and rRNAs are a major
      determinant of RNA stability. These tails are formed primarily by poly(A)
      polymerase I (PAP I) in wild-type strains or by polynucleotide phosphorylase
      (PNPase) in PAP I-deficient strains. In Streptomyces coelicolor it has been shown
      that mycelial RNAs display biochemical characteristics consistent with the
      presence of poly(A) tails. To confirm the occurrence of polyadenylation, rRNA and
      mRNA transcripts from S. coelicolor were isolated by oligo(dT)-dependent RT-PCR
      followed by cDNA cloning. One of the clones obtained was polyadenylated at a site
      corresponding to the mature 3' terminus of 16S rRNA, while two 23S rRNA cDNA
      clones were polyadenylated at precursor processing sites. Other clones identified
      polyadenylation sites internal to the coding regions of both 16S and 23S rRNAs,
      and redD and actII-orf4 mRNAs. While most rRNA cDNA clones displayed adenosine
      homopolymer tails, the poly(A) tails of three rRNAs and all the redD and actII
      orf4 clones consisted of a variety of heteropolymers. These results suggest that
      the enzyme primarily responsible for polyadenylation in S. coelicolor is PNPase
      rather than a PAP I homologue.

PMID- 11988517
TI  - The clavulanic acid biosynthetic cluster of Streptomyces clavuligerus: genetic
      organization of the region upstream of the car gene.
AB  - The genetic organization of the region upstream of the car gene of the clavulanic
      acid biosynthetic gene cluster of Streptomyces clavuligerus has been determined.
      Sequence analysis of a 12.1 kb region revealed the presence of 10 ORFs whose
      putative functions, according to database searches, are discussed. Three co
      transcriptional units are proposed: ORF10-11, ORF12-13 and ORF15-16-17-18.
      Potential transcriptional terminators were identified downstream of ORF11 (fd)
      and ORF15. Targeted disruption of ORF10 (cyp) gave rise to transformants unable
      to produce clavulanic acid, but with a considerably higher production of
      cephamycin C. Transformants inactivated at ORF14 had a remarkably lower
      production of clavulanic acid and similar production of cephamycin C. Significant
      improvements of clavulanic acid production, associated with a drop in cephamycin
      C biosynthesis, were obtained with transformants of S. clavuligerus harbouring
      multiple copies of plasmids carrying different constructions from the ORF10-14
      region. This information can be used to guide strain improvement programs,
      blending random mutagenesis and molecular cloning, to optimize the yield of
      clavulanic acid.

PMID- 11988518
TI  - An essential virulence protein of Brucella abortus, VirB4, requires an intact
      nucleoside-triphosphate-binding domain.
AB  - Brucella abortus is a facultative intracellular bacterium capable of surviving
      inside macrophages. The VirB complex, which is highly similar to conjugative DNA
      transfer apparatuses, is required for intracellular replication. A conserved NTP
      binding domain in VirB4 suggests that one or both proteins couple energy by NTP
      hydrolysis to transport of putative effector molecule(s). Here it is shown that a
      mutant strain of B. abortus that contains an in-frame deletion in virB4 is unable
      to replicate in macrophages and survives in mice. Intracellular replication and
      virulence in mice are fully restored by expressing virB4 in trans, indicating
      that VirB4 is essential for intracellular replication and virulence in mice. An
      alteration within the NTP-binding region of VirB4 by site-directed mutagenesis
      abolished complementation of a virB4 mutant, demonstrating that an intact NTP
      binding domain is critical for VirB4 function. Intracellular replication was
      inhibited in wild-type B. abortus after introducing a plasmid expressing a mutant
      VirB4 altered in the NTP-binding region. The dominant negative phenotype suggests
      that VirB4 either functions as a multimer or interacts with some other
      component(s) necessary for intracellular replication. Wild-type B. abortus
      containing phagosomes lack the glycoprotein LAMP-1, which is an indicator of the
      normal endocytic pathway. Mutant strains were found in phagosomes that co
      localized with LAMP-1, indicating that VirB4 containing the intact NTP-binding
      region is essential for evasion of fusion with lysosomes.

PMID- 11988519
TI  - Isogenic mutants of the cag pathogenicity island of Helicobacter pylori in the
      mouse model of infection: effects on colonization efficiency.
AB  - Strains of Helicobacter pylori that contain the cag pathogenicity island (cag
      PAI) are associated with increased virulence and severe clinical outcomes. To
      evaluate the role of the cag island in infection, isogenic null mutations were
      generated in two clinical isolates (SS1 and Iris1) with distinct genetic
      backgrounds. When tested for their ability to establish infection in the stomach
      of CD1/SPF mice, at the early phase of infection, strains in which cagE, ORF528,
      ORF527 or ORF525 were inactivated showed a reduced capacity to initiate
      colonization compared to the wild-type strain. Strains with a mutation in the
      ORF524 gene were more efficient than the other mutants, but still less efficient
      than the wild-type strain. Mutation in the effector protein, CagA, which is
      injected into host cells and tyrosine-phosphorylated, did not change the
      colonization efficiency. In conclusion, all cag genes analysed, with the
      exception of the effector protein, CagA, influenced the early phase of
      colonization in the mouse model of infection. These results suggest that the
      structure of the H. pylori secretion apparatus itself is involved in this
      process.

PMID- 11988520
TI  - Yersinia enterocolitica YopQ: strain-dependent cytosolic accumulation and post
      translational secretion.
AB  - YopQ in Yersinia enterocolitica (YopK in Yersinia pseudotuberculosis) is a type
      III secreted protein required for virulence of yersiniae. In this study YopQ
      expression, secretion and nucleotide sequences of the corresponding yopQ gene
      from different yersinia strains were analysed. The cytosolic accumulation
      differed significantly among serotypes of Y. enterocolitica. These differences
      might be attributable to variations in the nucleotide sequence and their
      consequences on mRNA secondary structure. An mRNA signal hypothesis has been
      proposed for YopQ, predicting the coupling of translation and secretion via an
      mRNA signal. This hypothesis claims a strictly co-translational secretion of YopQ
      without its intracellular accumulation. The presence of YopQ in the cytosol, even
      with a closed secretion apparatus, is demonstrated. Moreover, post-translational
      secretion of YopQ could be demonstrated. These findings do not support the mRNA
      signal hypothesis for co-translational secretion.

PMID- 11988521
TI  - Invasion by Neisseria meningitidis varies widely between clones and among
      nasopharyngeal mucosae derived from adult human hosts.
AB  - Colonization of the human nasopharynx is a feature of some species of Neisseria,
      and is a prerequisite of invasive meningococcal disease. The likelihood of
      colonization by Neisseria meningitidis varies widely between humans, and very few
      develop invasive disease. Explants of nasal mucosa derived from adult patients
      with non-allergic nasal obstruction were infected experimentally with Neisseria
      spp. At intervals over 18 h incubation, washed explants were homogenized, and
      viable bacteria were counted. To estimate bacterial invasion of mucosa, explants
      were exposed to 0.25% sodium taurocholate for 30 s prior to homogenization. N.
      meningitidis was recovered from the mucosa and the organism invaded and
      replicated within the tissue, in contrast to N. lactamica and N. animalis (n=9,
      P<0.008). N. meningitidis isolates of clones ET-5, ET-37 and lineage III were
      recovered from and invaded tissue, but strains of clones A4, A:subgroup I,
      A:subgroup III and A:subgroup IV-1 did not invade (n=6). To measure host
      variation, survival of N. meningitidis within nasal mucosa of 40 different human
      donors was measured. Intra-class correlation of replicates was 0.97, but the
      coefficient of variation of recovered viable counts was 1335% after 4 h and 77%
      after 18 h incubation. It is concluded that the distinctive colonization and
      disease potential of Neisseria spp. may be partly a consequence of their ability
      to invade and survive within human nasopharyngeal mucosa, but that this is
      influenced greatly by genetic or environmental factors operating on the host
      mucosa. This is consistent with the unpredictable epidemiology of meningococcal
      disease.

PMID- 11988522
TI  - Quorum sensing in Campylobacter jejuni: detection of a luxS encoded signalling
      molecule.
AB  - The expression of a wide variety of physiological functions in many bacterial
      species is modulated by quorum sensing, a population-dependent signalling
      mechanism that involves the production and detection of extracellular signalling
      molecules. The genome sequence of Campylobacter jejuni NCTC 11168 contains a gene
      encoding an orthologue of LuxS, which is required for autoinducer-2 (AI-2)
      production in other bacterial species, but does not contain genes predicted to
      encode any known acyl-homoserine lactone synthetase. This study demonstrates that
      C. jejuni produces functional AI-2 activity through the ability of cell-free
      extracts to specifically induce bioluminescence in Vibrio harveyi BB170, a
      reporter strain for quorum-sensing system 2. Production of this signalling
      compound was shown to be dependent upon the product of the C. jejuni luxS gene
      (Cj1198). While the luxS mutant showed comparable growth rate, resistance to
      oxidative stress and ability to invade Caco-2 cell monolayers to the parental
      strain, it exhibited decreased motility haloes in semisolid media, suggesting a
      role for quorum sensing in the regulation of motility.

PMID- 11988523
TI  - In vivo characterization of the psa genes from Streptococcus pneumoniae in
      multiple models of infection.
AB  - Differential fluorescence induction technology was used to identify promoters of
      Streptococcus pneumoniae genes that are expressed during lung infection of the
      mouse. Among the promoter clones that were identified multiple times was the psa
      promoter, which drives expression of the psaBCA operon. These genes have been
      identified previously and shown to encode a manganese permease system as well as
      play a role in the virulence of this organism. Mutations in psaB, psaC or psaA
      result in growth limitation in low manganese. The expression of the psa operon
      was examined in vivo and the virulence of deletion mutants of psaB, psaC, psaA
      and psaBCA was assessed in four different animal models of infection. The psa
      promoter was induced more than ten-fold in vivo using an intraperitoneal chamber
      implant model. The psaB, psaC and psaA mutants were completely attenuated in
      systemic, respiratory tract and otitis media infections. In addition, these
      mutants were unable to grow in an implanted peritoneal chamber, but growth was
      restored by the addition of manganese to the chambers.

PMID- 11988524
TI  - tRNA gene clusters at the 3' end of rRNA operons are specific to virulent
      subgroups of Streptococcus agalactiae strains, as demonstrated by molecular
      differential analysis at the population level.
AB  - The aim of this work was to characterize a 2.4 kb randomly amplified polymorphic
      DNA (RAPD) fragment described as a marker for a phylogenetic group of
      Streptococcus agalactiae strains significantly associated with neonatal
      meningitis. This fragment was analysed by cloning and sequencing, and showed that
      two types of tRNA gene cluster flank the 3' end of the rRNA operons in S.
      agalactiae strains. Both types of tRNA gene cluster act as markers for
      phylogenetic subgroups of strains within the species. One type could be used to
      distinguish two of the three virulent intraspecies subgroups to which most of the
      S. agalactiae strains able to invade the central nervous system of neonates
      belong. This raises the possibility that there is a link between these tRNA genes
      and the virulence of the bacterium. Based on this analysis, PCR primers were
      designed to determine whether S. agalactiae strains are likely to belong to
      lineages of organisms in which most of the highly virulent strains isolated from
      cerebrospinal fluid cluster. In addition, this work demonstrated that RAPD can be
      used to detect novel particularities within intraspecies variants of pathogens.

PMID- 11988525
TI  - Group A streptococcal RofA-type global regulators exhibit a strain-specific
      genomic presence and regulation pattern.
AB  - RofA-like protein (RALP) type regulators have been shown to exist in different
      forms in group A streptococci (GAS) and to regulate the expression of important
      bacterial adhesins. This study shows that the vast majority of strains from
      different GAS M serotypes carried a rofA virulence regulator gene in their genome
      and that this gene could be detected in combination with other RALP genes and
      RALP-dependent adhesin genes in a strain-specific manner. The gene encoding the
      Nra regulator was predominantly found in opacity factor (OF)-negative serotypes.
      When analysing a rofA mutant in a serotype M2 strain, the strain specificity was
      also found in the positive and negative regulatory functions of RALP genes as
      well as in the type and number of virulence genes and functions controlled by the
      RALP genes. Of 17 virulence-associated genes tested, only one, the putative
      streptolysin S gene, was observed to be derepressed in RALP mutants of three
      different GAS serotype strains. This strain-specific variability of RALP regulon
      sizes is associated with different patterns of host cell attachment and
      internalization. In addition, RofA2 was shown to control expression of the
      ribosomal protein gene rpsL. As a consequence, it was demonstrated for the first
      time in streptococci that aminoglycoside resistance mediated by rpsL expression
      is apparently controlled by a virulence gene regulator.

PMID- 11988526
TI  - The genetic structure of Escherichia coli populations in primary and secondary
      habitats.
AB  - Escherichia coli were recovered from the members of two two-person households and
      their associated septic tanks. The E. coli were isolated using selective and non
      selective isolation techniques, characterized using the method of multi-locus
      enzyme electrophoresis and screened for the presence of virulence factors
      associated with extra-intestinal disease by using PCR. The growth rate
      temperature relationships of strains from the two habitats were also determined.
      Temporal variation explained 25% of the observed electrophoretic type (ET)
      diversity in the humans. Among-host variation accounted for 29% of the observed
      allelic diversity. In one household, ET diversity of the E. coli population in
      the septic tank was significantly lower than ET diversity in the humans providing
      the inputs to the septic tank. Molecular analysis of variance revealed that, on
      average, strains recovered from the septic tank of this household were
      genetically distinct from strains recovered from the humans providing the faecal
      inputs to the septic tank. Further, the growth rate-temperature response of
      strains differed between strains isolated from the septic tank and strains
      isolated from the humans. Septic tank isolates grew better at low temperatures
      than strains isolated from humans, but more slowly at high temperatures compared
      to the human isolates. By contrast, no real differences in ET diversity, allelic
      diversity, or the growth characteristics of strains could be detected between
      strains from the humans and strains from the septic tank of the other household.
      The results of this study suggest there are strains of E. coli that are better
      "adapted" to conditions found in the external environment compared to strains
      isolated from the gastrointestinal habitat. Further, the finding that the
      numerically dominant clones and clonal diversity in secondary habitats can differ
      substantially from those found in the source populations will confound efforts to
      identify the sources of faecal pollution in the environment.

PMID- 11988527
TI  - Intraspecific diversity of Brevibacterium linens, Corynebacterium glutamicum and
      Rhodococcus erythropolis based on partial 16S rDNA sequence analysis and Fourier
      transform infrared (FT-IR) spectroscopy.
AB  - The intraspecific diversity of 31 strains of Brevibacterium linens, 27 strains of
      Corynebacterium glutamicum and 29 strains of Rhodococcus erythropolis was
      determined by partial 16S rDNA sequence analysis and Fourier-transform infrared
      (FT-IR) spectroscopy. As a prerequisite for the analyses, 27 strains derived from
      culture collections which had carried invalid or wrong species designations were
      reclassified in accordance with polyphasic taxonomical data. FT-IR spectroscopy
      proved to be a rapid and reliable method for screening for similar isolates and
      for identifying these actinomycetes at the species level. Two main conclusions
      emerged from the analyses. (1) Comparison of intraspecific 16S rDNA similarities
      suggested that R. erythropolis strains have a very low diversity, B. linens
      displays high diversity and C. glutamicum occupies an intermediate position. (2)
      No correlation of FT-IR spectral similarity and 16S rDNA sequence similarity
      below the species level (i.e. between strains of one species) was observed.
      Therefore, diversification of 16S rDNA sequences and microevolutionary change of
      the cellular components detected by FT-IR spectroscopy appear to be de-coupled.

PMID- 11988528
TI  - The cell surface protein Ag43 facilitates phage infection of Escherichia coli in
      the presence of bile salts and carbohydrates.
AB  - It was found that infection of Escherichia coli by bacteriophage lambda is
      inhibited in the presence of certain bile salts and carbohydrates when cells are
      in the "OFF" state for production of the phase-variable cell surface protein
      antigen 43 (Ag43). The inhibition of phage growth was found to be due to a
      significant impairment in the process of phage adsorption. Expression of the gene
      encoding Ag43 (agn43) from a plasmid or inactivation of the oxyR gene (encoding
      an activator of genes important for defence against oxidative stress) suppressed
      this inhibition. A mutation, rpoA341, in the gene encoding the alpha subunit of
      RNA polymerase also facilitated phage adsorption in the presence of bile salts
      and carbohydrates. The rpoA341 mutation promoted efficient production of Ag43 in
      a genetic background that would otherwise be in the "OFF" phase for expression of
      the agn43 gene. Analysis of a reporter gene fusion demonstrated that the promoter
      for the agn43 gene was more active in the rpoA341 mutant than in the otherwise
      isogenic rpoA(+) strain. The combined inhibitory action of bile salts and
      carbohydrates on phage adsorption and the abolition of this inhibition by
      production of Ag43 was not restricted to lambda, as a similar phenomenon was
      observed for the coliphages P1 and T4.

PMID- 11988529
TI  - Regulation of bacterial motility in response to low pH in Escherichia coli: the
      role of H-NS protein.
AB  - The effect of detrimental conditions on bacterial motility in Escherichia coli
      was investigated. Expression profiling of mutant E. coli strains by DNA arrays
      and analysis of phenotypic traits demonstrated that motility and low-pH
      resistance are coordinately regulated. Analysis of transcriptional fusions
      suggests that bacterial motility in response to an acidic environment is mediated
      via the control by H-NS of flhDC expression. Moreover, the results suggested that
      the presence of an extended mRNA 5' end and DNA topology are required in this
      process. Finally, the presence of a similar regulatory region in several Gram
      negative bacteria implies that this mechanism is largely conserved.

PMID- 11988530
TI  - The regulation of Enzyme IIA(Glc) expression controls adenylate cyclase activity
      in Escherichia coli.
AB  - During the last few years, several genes, such as pap, bgl and flhDC, have been
      shown to be coregulated by the histone-like nucleoid-structuring (H-NS) protein
      and the cyclic AMP-catabolite activator protein (cAMP/CAP) complex, suggesting an
      interaction between both systems in the control of some cellular functions. In
      this study, the possible effect of H-NS on the cAMP level was investigated. In a
      CAP-deficient strain, the presence of an hns mutation results in a strong
      reduction in the amount of cAMP, due to a decrease in adenylate cyclase activity.
      This is caused by the reduced expression of crr, which encodes the Enzyme
      IIA(Glc) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS),
      from its specific P2 promoter. This leads to a twofold reduction in the global
      amount of Enzyme IIA(Glc), the adenylate cyclase activator, responsible for the
      decrease in adenylate cyclase activity observed in the hns crp strain.

PMID- 11988531
TI  - Effect of vfr mutation on global gene expression and catabolite repression
      control of Pseudomonas aeruginosa.
AB  - Vfr of Pseudomonas aeruginosa is 91% similar to the cAMP receptor protein (CRP)
      of Escherichia coli. Based on the high degree of sequence homology between the
      two proteins, the question arose whether Vfr had a global regulatory effect on
      gene expression for P. aeruginosa as CRP did for E. coli. This report provides
      two-dimensional polyacrylamide gel electrophoretic evidence that Vfr is a global
      regulator of gene expression in P. aeruginosa. In a vfr101::aacC1 null mutant, at
      least 43 protein spots were absent or decreased when compared to the proteome
      pattern of the parent strain. In contrast, 17 protein spots were absent or
      decreased in the parent strain when compared to the vfr101::aacC1 mutant. Thus, a
      mutation in vfr affected production of at least 60 proteins in P. aeruginosa. In
      addition, the question whether Vfr and CRP shared similar mechanistic
      characteristics was addressed. To ascertain whether Vfr, like CRP, can bind cAMP,
      Vfr and CRP were purified to homogeneity and their apparent dissociation
      constants (K(d)) for binding to cAMP were determined. The K(d) values were 1.6
      microM for Vfr and 0.4 microM for CRP, suggesting that these proteins have a
      similar affinity for cAMP. Previously the authors had demonstrated that Vfr could
      complement a crp mutation and modulate catabolite repression in E. coli. This
      study presents evidence that Vfr binds to the E. coli lac promoter and that this
      binding requires the presence of cAMP. Finally, the possible involvement of Vfr
      in catabolite repression control in P. aeruginosa was investigated. It was found
      that succinate repressed production of mannitol dehydrogenase, glucose-6
      phosphate dehydrogenase, amidase and urocanase both in the parent and in two vfr
      null mutants. This implied that catabolite repression control was not affected by
      the vfr null mutation. In support of this, the cloned vfr gene failed to
      complement a mutation in the P. aeruginosa crc gene. Thus, although Vfr is
      structurally similar to CRP, and is a global regulator of gene expression in P.
      aeruginosa, Vfr is not required for catabolite repression control in this
      bacterium.

PMID- 11988532
TI  - Use of an arrayed promoter-probe library for the identification of macrophage
      regulated genes in Mycobacterium tuberculosis.
AB  - The survival of Mycobacterium tuberculosis within the human host after infection,
      especially within macrophages, is likely to require the activation of a number of
      mycobacterial genes. To identify such genes, a promoter-probe library was
      constructed in which fragments of M. tuberculosis H37Rv DNA were inserted
      upstream of a lacZ reporter gene, using an Escherichia coli-mycobacterial shuttle
      vector. Mycobacterium bovis Bacille Calmette-Guerin (BCG) was subsequently
      transformed with this library and 4800 BCG clones were arrayed in a 96-well
      microtitre format, enabling the testing of individual clones for promoter
      activity under a variety of conditions. From preliminary screening, 41 clones
      were selected that exhibited upregulation of lacZ expression when subjected to
      acidified sodium nitrite. Subsequent sequence analyses identified 26 of these
      clones as containing potential promoters. After measuring lacZ expression in BCG
      clones recovered from a THP-1 macrophage cell line, three genes were selected for
      assessment of their expression in M. tuberculosis during macrophage infection, by
      real-time RT-PCR. Two of these genes, Rv1265 (with unknown function) and Rv2711
      (encoding the iron-dependent repressor protein IdeR), showed evidence of being
      upregulated within macrophages.

PMID- 11988533
TI  - Formation and resuscitation of "non-culturable" cells of Rhodococcus rhodochrous
      and Mycobacterium tuberculosis in prolonged stationary phase.
AB  - After growth of Rhodococcus rhodochrous in Sauton's medium, and further
      incubation for about 60 h in stationary phase, there was a transient (up to 5
      log) decrease in the c.f.u. count, whereas the total count remained similar to
      its initial value. At the point of minimal viability, the most probable number
      (MPN) count was 10 times greater than the c.f.u. count. This difference was
      further magnified by 3-4 logs (giving values close to the total count) by
      incorporating supernatant taken from growing cultures. A small protein similar to
      Rpf (resuscitation-promoting factor of Micrococcus luteus) appeared to be
      responsible for some of the activity in the culture supernatant. The formation of
      "non-culturable" cells of the "Academia" strain of Mycobacterium tuberculosis was
      similarly observed following growth in Sauton's medium containing Tween 80 in
      sealed culture vessels, and further incubation for an extended stationary phase.
      This resulted in the formation, 4-5 months post-inoculation, of a homogeneous
      population of ostensibly "non-culturable" cells (zero c.f.u.). Remarkably, the
      MPN count for these cultures was 10(5) organisms ml(-1), and this value was
      further increased by one log using supernatant from an actively growing culture.
      Populations of "non-culturable" cells of Mycobacterium tuberculosis were also
      obtained by the filtration of "clumpy" cultures, which were grown in the absence
      of Tween 80. These small cells could only be grown in liquid medium (MPN) and
      their viability was enhanced by the addition of culture supernatant or Rpf. The
      "non-culturable" cells that accumulated during prolonged stationary phase in both
      the R. rhodochrous and the Mycobacterium tuberculosis cultures were small ovoid
      and coccoid forms with an intact permeability barrier, but with undetectable
      respiratory activity. The authors consider these non-culturable bacteria to be
      dormant. The observed activity of culture supernatants and Rpf with "non
      culturable" bacterial suspensions invites the speculation that one, or more, of
      the cognate Mycobacterium tuberculosis Rpf-like molecule(s) could be involved in
      mechanisms of latency and reactivation of tuberculosis in vivo.

PMID- 11988534
TI  - Regulatory interactions between the Pho and sigma(B)-dependent general stress
      regulons of Bacillus subtilis.
AB  - When Bacillus subtilis is subjected to phosphate starvation, the Pho and sigma(B)
      dependent general stress regulons are activated to elicit, respectively, specific
      and non-specific responses to this nutrient-limitation stress. A set of isogenic
      mutants, with a beta-galactosidase reporter gene transcriptionally fused to the
      inactivated target gene, was used to identify genes of unknown function that are
      induced or repressed under phosphate limitation. Nine phosphate-starvation
      induced (psi) genes were identified: yhaX, yhbH, ykoL and yttP were regulated by
      the PhoP-PhoR two-component system responsible for controlling the expression of
      genes in the Pho regulon, while ywmG (renamed csbD), yheK, ykzA, ysnF and yvgO
      were dependent on the alternative sigma factor sigma(B), which controls the
      expression of the general stress genes. Genes yhaX and yhbH are unique members of
      the Pho regulon, since they are phosphate-starvation induced via PhoP-PhoR from a
      sporulation-specific sigma(E) promoter or a promoter that requires the product of
      a sigma(E)-dependent gene. Null mutations in key regulatory genes phoR and sigB
      showed that the Pho and sigma(B)-dependent general stress regulons of Bacillus
      subtilis interact to modulate the levels at which each are activated.

PMID- 11988535
TI  - Design and control of wave propagation patterns in excitable media.
AB  - Intricate patterns of wave propagation are exhibited in a chemical reaction
      diffusion system with spatiotemporal feedback. Wave behavior is controlled by
      feedback-regulated excitability gradients that guide propagation in specified
      directions. Waves interacting with boundaries and with other waves are observed
      when interaction terms are incorporated into the control algorithm.
      Spatiotemporal feedback offers wide flexibility for designing and controlling
      wave behavior in excitable media.

PMID- 11988536
TI  - Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's
      disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disease caused by
      expansion of a polyglutamine tract in the huntingtin protein. Transcriptional
      dysregulation has been implicated in HD pathogenesis. Here, we report that
      huntingtin interacts with the transcriptional activator Sp1 and coactivator
      TAFII130. Coexpression of Sp1 and TAFII130 in cultured striatal cells from wild
      type and HD transgenic mice reverses the transcriptional inhibition of the
      dopamine D2 receptor gene caused by mutant huntingtin, as well as protects
      neurons from huntingtin-induced cellular toxicity. Furthermore, soluble mutant
      huntingtin inhibits Sp1 binding to DNA in postmortem brain tissues of both
      presymptomatic and affected HD patients. Understanding these early molecular
      events in HD may provide an opportunity to interfere with the effects of mutant
      huntingtin before the development of disease symptoms.

PMID- 11988537
TI  - A natural product that lowers cholesterol as an antagonist ligand for FXR.
AB  - Extracts of the resin of the guggul tree (Commiphora mukul) lower LDL (low
      density lipoprotein) cholesterol levels in humans. The plant sterol guggulsterone
      [4,17(20)-pregnadiene-3,16-dione] is the active agent in this extract. We show
      that guggulsterone is a highly efficacious antagonist of the farnesoid X receptor
      (FXR), a nuclear hormone receptor that is activated by bile acids. Guggulsterone
      treatment decreases hepatic cholesterol in wild-type mice fed a high-cholesterol
      diet but is not effective in FXR-null mice. Thus, we propose that inhibition of
      FXR activation is the basis for the cholesterol-lowering activity of
      guggulsterone. Other natural products with specific biologic effects may modulate
      the activity of FXR or other relatively promiscuous nuclear hormone receptors.

PMID- 11988538
TI  - Research assessment in the UK.

PMID- 11988539
TI  - Pediatric drug trials. Challenge to FDA's authority may end up giving it more.

PMID- 11988540
TI  - Paleobotany. Fossil plant hints how first flowers bloomed.

PMID- 11988541
TI  - Weapons labs. DOE delays hiring of Livermore head.

PMID- 11988542
TI  - Alcoholism research. Stressed mutant mice hit the bottle.

PMID- 11988543
TI  - Population studies. U.K.'s mass appeal for disease insights.

PMID- 11988544
TI  - Genome research. Venter is back with two new institutes.

PMID- 11988545
TI  - Climate change. A single climate mover for Antarctica.

PMID- 11988546
TI  - National security. Pentagon proposal worries researchers.

PMID- 11988547
TI  - Research funding. Europe begins work on modest new agency.

PMID- 11988548
TI  - Proteomics. Public-private group maps out initiatives.

PMID- 11988549
TI  - Science indicators. NSF report paints a global picture.

PMID- 11988550
TI  - Astronomy. Tuning in the radio sky.

PMID- 11988551
TI  - Astronomy. Space communication for the video age.

PMID- 11988552
TI  - Astronomy. Seeking peace in a radio-loud world.

PMID- 11988553
TI  - Assyria. Bringing a long-lost library back to life.

PMID- 11988554
TI  - American Association of Physical Anthropologists meeting. Humans' head start: new
      views of brain evolution.

PMID- 11988555
TI  - Drug delivery. Breaching the membrane.

PMID- 11988556
TI  - Portraits of science. Damn the torpedoes. Full speed ahead!

PMID- 11988557
TI  - Cell biology. The different hues of lipid rafts.

PMID- 11988558
TI  - Cell biology. Fats, flies, and palmitate.

PMID- 11988559
TI  - Self-assembly. Persistence pays off.

PMID- 11988560
TI  - Physics. Superconducting qubits--a major roadblock dissolved?

PMID- 11988561
TI  - Microbiology. Subversion of Schwann cells and the leper's bell.

PMID- 11988562
TI  - Planetary biology--paleontological, geological, and molecular histories of life.
AB  - The history of life on Earth is chronicled in the geological strata, the fossil
      record, and the genomes of contemporary organisms. When examined together, these
      records help identify metabolic and regulatory pathways, annotate protein
      sequences, and identify animal models to develop new drugs, among other features
      of scientific and biomedical interest. Together, planetary analysis of genome and
      proteome databases is providing an enhanced understanding of how life interacts
      with the biosphere and adapts to global change.

PMID- 11988563
TI  - Axonal self-destruction and neurodegeneration.
AB  - Neurons seem to have at least two self-destruct programs. Like other cell types,
      they have an intracellular death program for undergoing apoptosis when they are
      injured, infected, or not needed. In addition, they apparently have a second,
      molecularly distinct self-destruct program in their axon. This program is
      activated when the axon is severed and leads to the rapid degeneration of the
      isolated part of the cut axon. Do neurons also use this second program to prune
      their axonal tree during development and to conserve resources in response to
      chronic insults?

PMID- 11988564
TI  - Female eavesdropping on male song contests in songbirds.

PMID- 11988565
TI  - A SN2 reaction that avoids its deep potential energy minimum.
AB  - Chemical dynamics trajectory simulations were used to study the atomic-level
      mechanisms of the OH- + CH3F --> CH3OH + F- SN2 nucleophilic substitution
      reaction. The reaction dynamics, from the [OH...CH3...F]- central barrier to the
      reaction products, are simulated by ab initio direct dynamics. The reaction's
      potential energy surface has a deep minimum in the product exit channel arising
      from the CH3OH...F- hydrogen-bonded complex. Statistical theories of unimolecular
      reaction rates assume that the reactive system becomes trapped in this minimum
      and forms an intermediate, with random redistribution of its vibrational energy,
      but the majority of the trajectories (90%) avoided this potential energy minimum
      and instead dissociated directly to products. This finding is discussed in terms
      of intramolecular vibrational energy redistribution (IVR) and the relation
      between IVR and molecular structure. The finding of this study may be applicable
      to other reactive systems where there is a hierarchy of time scales for
      intramolecular motions and thus inefficient IVR.

PMID- 11988566
TI  - Regulation of SREBP processing and membrane lipid production by phospholipids in
      Drosophila.
AB  - Animal cells exert exquisite control over the physical and chemical properties of
      their membranes, but the mechanisms are obscure. We show that
      phosphatidylethanolamine, the major phospholipid in Drosophila, controls the
      release of sterol regulatory element-binding protein (SREBP) from Drosophila cell
      membranes, exerting feedback control on the synthesis of fatty acids and
      phospholipids. The finding that SREBP processing is controlled by different
      lipids in mammals and flies (sterols and phosphatidylethanolamine, respectively)
      suggests that an essential function of SREBP is to monitor cell membrane
      composition and to adjust lipid synthesis accordingly.

PMID- 11988567
TI  - Direct synthesis of long single-walled carbon nanotube strands.
AB  - In the processes that are used to produce single-walled nanotubes (electric arc,
      laser ablation, and chemical vapor deposition), the typical lengths of tangled
      nanotube bundles reach several tens of micrometers. We report that long nanotube
      strands, up to several centimeters in length, consisting of aligned single-walled
      nanotubes can be synthesized by the catalytic pyrolysis of n-hexane with an
      enhanced vertical floating technique. The long strands of nanotubes assemble
      continuously from arrays of nanotubes, which are intrinsically long.

PMID- 11988568
TI  - Manipulating the quantum state of an electrical circuit.
AB  - We have designed and operated a superconducting tunnel junction circuit that
      behaves as a two-level atom: the "quantronium." An arbitrary evolution of its
      quantum state can be programmed with a series of microwave pulses, and a
      projective measurement of the state can be performed by a pulsed readout
      subcircuit. The measured quality factor of quantum coherence Qphi approximately
      25,000 is sufficiently high that a solid-state quantum processor based on this
      type of circuit can be envisioned.

PMID- 11988569
TI  - Coherent temporal oscillations of macroscopic quantum states in a Josephson
      junction.
AB  - We report the generation and observation of coherent temporal oscillations
      between the macroscopic quantum states of a Josephson tunnel junction by applying
      microwaves with frequencies close to the level separation. Coherent temporal
      oscillations of excited state populations were observed by monitoring the
      junction's tunneling probability as a function of time. From the data, the lower
      limit of phase decoherence time was estimated to be about 5 microseconds.

PMID- 11988570
TI  - Ordering of quantum dots using genetically engineered viruses.
AB  - A liquid crystal system was used for the fabrication of a highly ordered
      composite material from genetically engineered M13 bacteriophage and zinc sulfide
      (ZnS) nanocrystals. The bacteriophage, which formed the basis of the self
      ordering system, were selected to have a specific recognition moiety for ZnS
      crystal surfaces. The bacteriophage were coupled with ZnS solution precursors and
      spontaneously evolved a self-supporting hybrid film material that was ordered at
      the nanoscale and at the micrometer scale into approximately 72-micrometer
      domains, which were continuous over a centimeter length scale. In addition,
      suspensions were prepared in which the lyotropic liquid crystalline phase
      behavior of the hybrid material was controlled by solvent concentration and by
      the use of a magnetic field.

PMID- 11988571
TI  - Interpretation of recent Southern Hemisphere climate change.
AB  - Climate variability in the high-latitude Southern Hemisphere (SH) is dominated by
      the SH annular mode, a large-scale pattern of variability characterized by
      fluctuations in the strength of the circumpolar vortex. We present evidence that
      recent trends in the SH tropospheric circulation can be interpreted as a bias
      toward the high-index polarity of this pattern, with stronger westerly flow
      encircling the polar cap. It is argued that the largest and most significant
      tropospheric trends can be traced to recent trends in the lower stratospheric
      polar vortex, which are due largely to photochemical ozone losses. During the
      summer-fall season, the trend toward stronger circumpolar flow has contributed
      substantially to the observed warming over the Antarctic Peninsula and Patagonia
      and to the cooling over eastern Antarctica and the Antarctic plateau.

PMID- 11988572
TI  - Archaefructaceae, a new basal angiosperm family.
AB  - Archaefructaceae is proposed as a new basal angiosperm family of herbaceous
      aquatic plants. This family consists of the fossils Archaefructus liaoningensis
      and A. sinensis sp. nov. Complete plants from roots to fertile shoots are known.
      Their age is a minimum of 124.6 million years from the Yixian Formation,
      Liaoning, China. They are a sister clade to all angiosperms when their characters
      are included in a combined three-gene molecular and morphological analysis. Their
      reproductive axes lack petals and sepals and bear stamens in pairs below
      conduplicate carpels.

PMID- 11988573
TI  - Mammal population losses and the extinction crisis.
AB  - The disappearance of populations is a prelude to species extinction. No
      geographically explicit estimates have been made of current population losses of
      major indicator taxa. Here we compare historic and present distributions of 173
      declining mammal species from six continents. These species have collectively
      lost over 50% of their historic range area, mostly where human activities are
      intensive. This implies a serious loss of ecosystem services and goods. It also
      signals a substantial threat to species diversity.

PMID- 11988574
TI  - Genomewide analysis of mRNA processing in yeast using splicing-specific
      microarrays.
AB  - Introns interrupt almost every eukaryotic protein-coding gene, yet how the
      splicing apparatus interprets the genome during messenger RNA (mRNA) synthesis is
      poorly understood. We designed microarrays to distinguish spliced from unspliced
      RNA for each intron-containing yeast gene and measured genomewide effects on
      splicing caused by loss of 18 different mRNA processing factors. After
      accommodating changes in transcription and decay by using gene-specific indexes,
      functional relationships between mRNA processing factors can be identified
      through their common effects on spliced and unspliced RNA. Groups of genes with
      different dependencies on mRNA processing factors are also apparent. Quantitative
      polymerase chain reactions confirm the array-based finding that Prp17p and Prp18p
      are not dispensable for removal of introns with short branchpoint-to-3' splice
      site distances.

PMID- 11988575
TI  - Specificity and stability in topology of protein networks.
AB  - Molecular networks guide the biochemistry of a living cell on multiple levels:
      Its metabolic and signaling pathways are shaped by the network of interacting
      proteins, whose production, in turn, is controlled by the genetic regulatory
      network. To address topological properties of these two networks, we quantified
      correlations between connectivities of interacting nodes and compared them to a
      null model of a network, in which all links were randomly rewired. We found that
      for both interaction and regulatory networks, links between highly connected
      proteins are systematically suppressed, whereas those between a highly connected
      and low-connected pairs of proteins are favored. This effect decreases the
      likelihood of cross talk between different functional modules of the cell and
      increases the overall robustness of a network by localizing effects of
      deleterious perturbations.

PMID- 11988576
TI  - Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live
      cells.
AB  - Many proteins associated with the plasma membrane are known to partition into
      submicroscopic sphingolipid- and cholesterol-rich domains called lipid rafts, but
      the determinants dictating this segregation of proteins in the membrane are
      poorly understood. We suppressed the tendency of Aequorea fluorescent proteins to
      dimerize and targeted these variants to the plasma membrane using several
      different types of lipid anchors. Fluorescence resonance energy transfer
      measurements in living cells revealed that acyl but not prenyl modifications
      promote clustering in lipid rafts. Thus the nature of the lipid anchor on a
      protein is sufficient to determine submicroscopic localization within the plasma
      membrane.

PMID- 11988577
TI  - Large-scale transcriptional activity in chromosomes 21 and 22.
AB  - The sequences of the human chromosomes 21 and 22 indicate that there are
      approximately 770 well-characterized and predicted genes. In this study,
      empirically derived maps identifying active areas of RNA transcription on these
      chromosomes have been constructed with the use of cytosolic polyadenylated RNA
      obtained from 11 human cell lines. Oligonucleotide arrays containing probes
      spaced on average every 35 base pairs along these chromosomes were used. When
      compared with the sequence annotations available for these chromosomes, it is
      noted that as much as an order of magnitude more of the genomic sequence is
      transcribed than accounted for by the predicted and characterized exons.

PMID- 11988578
TI  - Neurofibromas in NF1: Schwann cell origin and role of tumor environment.
AB  - Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited
      genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose
      functional loss results in the development of benign neurofibromas that can
      progress to malignancy. Neurofibromas are complex tumors composed of axonal
      processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through
      use of a conditional (cre/lox) allele, we show that loss of NF1 in the Schwann
      cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated
      tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic
      as well as heterozygosity in non-neoplastic cells. The requirement for a
      permissive haploinsufficient environment to allow tumorigenesis may have
      therapeutic implications for NF1 and other familial cancers.

PMID- 11988579
TI  - Contact-dependent demyelination by Mycobacterium leprae in the absence of immune
      cells.
AB  - Demyelination results in severe disability in many neurodegenerative diseases and
      nervous system infections, and it is typically mediated by inflammatory
      responses. Mycobacterium leprae, the causative organism of leprosy, induced rapid
      demyelination by a contact-dependent mechanism in the absence of immune cells in
      an in vitro nerve tissue culture model and in Rag1-knockout (Rag1-/-) mice, which
      lack mature B and T lymphocytes. Myelinated Schwann cells were resistant to M.
      leprae invasion but undergo demyelination upon bacterial attachment, whereas
      nonmyelinated Schwann cells harbor intracellular M. leprae in large numbers.
      During M. leprae-induced demyelination, Schwann cells proliferate significantly
      both in vitro and in vivo and generate a more nonmyelinated phenotype, thereby
      securing the intracellular niche for M. leprae.

PMID- 11988580
TI  - Enhanced and delayed stress-induced alcohol drinking in mice lacking functional
      CRH1 receptors.
AB  - There is a relation between stress and alcohol drinking. We show that the
      corticotropin-releasing hormone (CRH) system that mediates endocrine and
      behavioral responses to stress plays a role in the control of long-term alcohol
      drinking. In mice lacking a functional CRH1 receptor, stress leads to enhanced
      and progressively increasing alcohol intake. The effect of repeated stress on
      alcohol drinking behavior appeared with a delay and persisted throughout life. It
      was associated with an up-regulation of the N-methyl-d-aspartate receptor subunit
      NR2B. Alterations in the CRH1 receptor gene and adaptional changes in NR2B
      subunits may constitute a genetic risk factor for stress-induced alcohol drinking
      and alcoholism.

PMID- 11988581
TI  - Awareness: the first step to action.

PMID- 11988582
TI  - Carotid intima-media thickness in familial combined hyperlipidemia and LDL size.

PMID- 11988583
TI  - Measuring quality of life after stroke using the SF-36.

PMID- 11988584
TI  - Race and sex differences in the effects of dietary potassium intake on the risk
      of stroke.

PMID- 11988585
TI  - Prevalence and risk factors of silent brain infarcts in the population.

PMID- 11988586
TI  - Cerebral atherosclerosis causes neurogenic hypertension.

PMID- 11988587
TI  - Multiple panel of biomarkers for TIA/stroke evaluation.

PMID- 11988588
TI  - Dietary intake of folate and risk of stroke in US men and women: NHANES I
      Epidemiologic Follow-up Study. National Health and Nutrition Examination Survey.
AB  - BACKGROUND AND PURPOSE: Few population-based studies have examined the
      relationship between dietary intake of folate and risk of stroke and
      cardiovascular disease (CVD). This study examines the association between dietary
      intake of folate and the subsequent risk of stroke and CVD. METHODS: Study
      participants included 9764 US men and women aged 25 to 74 years who participated
      in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up
      Study (NHEFS) and were free of CVD at baseline. Dietary intake of folate was
      assessed at baseline using a 24-hour dietary recall and calculated using ESHA
      software. Incidence data for stroke and CVD were obtained from medical records
      and death certificates. RESULTS: Over an average of 19 years of follow-up, 926
      incident stroke events and 3758 incident CVD events were documented. The relative
      risk (RR) was 0.79 (95% confidence interval [CI], 0.63 to 0.99, P=0.03 for trend)
      for incident stroke events and 0.86 (95% CI: 0.78 to 0.95, P<0.001 for trend) for
      incident CVD events in the highest quartile of dietary folate intake (median,
      405.0 microg/day) compared with those in the lowest quartile (median, 99.0
      microg/day), after adjustment for established cardiovascular risk factors and
      dietary factors. CONCLUSIONS: Our findings indicate an inverse relationship
      between dietary intake of folate and subsequent risk of stroke and CVD.
      Increasing dietary intake of folate from food sources may be an important
      approach to the prevention of CVD in the US population.

PMID- 11988589
TI  - Genetic and environmental risk factors for intracerebral hemorrhage: preliminary
      results of a population-based study.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has a 30-day mortality
      rate of 40% to 50% and lacks a proven treatment. We report a preplanned, midpoint
      analysis of the first population-based, case-control study that examines both
      genetic and environmental risk factors of ICH. METHODS: We prospectively
      identified cases of hemorrhagic stroke at all 16 hospitals in the Greater
      Cincinnati/Northern Kentucky region. All cases underwent medical record and
      neuroimaging review. Cases enrolled in the direct interview and genetic sampling
      arm of the study were matched to population-based control subjects by age, race,
      and sex. Multivariable logistic regression was performed to identify significant
      independent risk factors. RESULTS: We enrolled 188 cases of ICH (67 lobar, 121
      nonlobar) and 366 control subjects in the direct interview arm of the study.
      Significant independent risk factors for lobar ICH included the presence of an
      apolipoprotein E2 or E4 allele, frequent alcohol use, prior stroke, and first
      degree relative with ICH. Significant independent risk factors for nonlobar ICH
      were hypertension, prior stroke, and first-degree relative with ICH. An
      increasing level of education was associated with a decreased risk of nonlobar
      ICH. The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29%, and
      the attributable risk of hypertension for nonlobar ICH was 54%. CONCLUSIONS:
      There is significant epidemiological evidence that the pathophysiology of ICH
      varies by location. We estimate that a third of all cases of lobar ICH are
      attributable to possession of an apolipoprotein E4 or E2 allele and that half of
      all cases of nonlobar ICH are attributable to hypertension.

PMID- 11988590
TI  - Sex differences in US mortality rates for stroke and stroke subtypes by
      race/ethnicity and age, 1995-1998.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke accounts for 70% to 80% of all strokes,
      but intracerebral and subarachnoid hemorrhagic strokes have greater fatality. Age
      standardized death rates from overall stroke are higher among men than women, but
      little is known about sex differences in stroke subtype mortality by
      race/ethnicity. METHODS: We analyzed 1995 to 1998 national death certificate data
      to compare sex-specific age-standardized death rates (per 100 000) for ischemic
      stroke (n=507 256), intracerebral hemorrhagic stroke (n=98 709), and subarachnoid
      hemorrhagic stroke (n=27 334) among whites, blacks, American Indians/Alaska
      Natives, Asians/Pacific Islanders, and Hispanics. We calculated rate ratios and
      95% CIs comparing women with men within age and racial/ethnic groups. RESULTS:
      Age-specific rates of ischemic and intracerebral hemorrhagic stroke deaths were
      lower for women than for men aged 25 to 44 and 45 to 64 years but were higher for
      ischemic stroke among older women, aged > or =65 years. Only among whites did
      women have higher age-standardized rates of ischemic stroke. Age-standardized
      death rates for intracerebral hemorrhagic stroke among women were lower than or
      similar to those among men in all racial/ethnic groups. Women had higher risk of
      death from subarachnoid hemorrhagic; this sex differential increased with age.
      CONCLUSIONS: The female-to-male mortality ratio differs for stroke subtypes by
      race/ethnicity and age. A primary public health effort should focus on increasing
      the awareness of stroke symptoms, particularly among people at high risk, to
      decrease delay in early detection and effective stroke treatment.

PMID- 11988591
TI  - Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study:
      oral contraceptives and the risk of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Epidemiological studies have shown an increased risk of
      venous thrombosis in women taking third-generation oral contraceptives, ie, those
      containing the progestogens desogestrel or gestodene. This study assesses the
      risk of ischemic stroke with several types of oral contraceptives. METHODS: A
      multicenter, population-based, case-control study was performed in 9 Dutch
      centers in women aged 18 to 49 years. Women with a first ischemic stroke were
      compared with control women without vascular diseases. The control subjects were
      recruited by random-digit dialing and were stratified by age, area of residence,
      and year of stroke. All patients and control subjects filled in a questionnaire
      about the use of oral contraceptives and risk factors for ischemic stroke. Odds
      ratios were adjusted for the stratification factors. RESULTS: Two hundred three
      women with an ischemic stroke and 925 control women were included. The risk of
      stroke in women using any type of oral contraceptives versus none was 2.3 (95% CI
      1.6 to 3.3). Current users of first-generation oral contraceptives had an odds
      ratio of 1.7 (95% CI 0.7 to 4.4). Low-dose second-generation oral contraceptives
      increased the risk of stroke 2.4 times (95% CI 1.6 to 3.7), and third-generation
      oral contraceptives increased the risk of stroke 2.0 times (95% CI 1.2 to 3.5).
      The risk of stroke in women using third-generation oral contraceptives was not
      different from that in women using second-generation oral contraceptives (odds
      ratio 1.0, 95% CI 0.6 to 1.8). CONCLUSIONS: Third-generation oral contraceptives
      (containing desogestrel or gestodene) confer the same risk of first ischemic
      stroke as second-generation oral contraceptives (containing levonorgestrel).

PMID- 11988592
TI  - Trends in stroke prevalence between 1973 and 1991 in the US population 25 to 74
      years of age.
AB  - BACKGROUND AND PURPOSE: Stroke mortality in the United States has declined since
      1900. Primary prevention of stroke incidence did not decline and may have
      increased during the 1980s, whereas survival after stroke improved substantially
      during the 1970s and 1980s. The effect of these trends on the prevalence and
      number of stroke survivors in the United States has not been determined. METHODS:
      The prevalence and number of noninstitutionalized stroke survivors in the United
      States was estimated through self-report for 3 time periods: 1971-1975, 1976
      1980, and 1988-1994, using data from the National Health and Nutrition
      Examination Surveys (NHANES) I, II, and III, respectively. Prevalence and number
      of stroke survivors were analyzed by age (25 to 59 and 60 to 74 years), race (non
      Hispanic whites/Mexican-Americans and non-Hispanic blacks), and sex. Estimates
      were limited to the US population ages 25 to 74 years because NHANES I and II did
      not include persons older than 75 years. RESULTS: The age-, race-, and sex
      adjusted prevalence of stroke increased from 1.41% to 1.87% from 1971-1975 to
      1988-1994, an average increase of 7.5% (95% confidence interval: -2%, +18%) for
      each 5-year period during this time. Additionally, during this period, the
      estimated number of noninstitutionalized stroke survivors increased by 930 000
      (95% CI: 300 000 to 1.6 million) from 1.5 million to 2.4 million. Additionally,
      the average "health in general" among stroke survivors was similar in all 3
      periods. CONCLUSIONS: These data point to the increasing importance of the care
      and rehabilitation of stroke survivors.

PMID- 11988593
TI  - Bone formation in carotid plaques: a clinicopathological study.
AB  - BACKGROUND AND PURPOSE: Bone formation and dystrophic calcification are present
      in carotid endarterectomy plaques. The clinical significance of these findings is
      unknown. The purpose of this study was to determine whether bone formation and
      extensive dystrophic calcification are associated with stable plaques and
      protective against ischemic vascular events. METHODS: Carotid endarterectomy
      plaques were collected from 142 patients (94 men) with carotid stenosis. The
      specimens were evaluated for lamellar bone formation, dystrophic calcifications,
      inflammatory infiltrates, neovascularization, and histological type or grade of
      plaque according to a standard AHA grading system. Immunohistochemical staining
      was performed to identify vascular endothelial cells in neovascularization
      (factor VIII) and lymphocytes. Clinical data, including history of
      cerebrovascular and cardiovascular events, were recorded at the time of surgery.
      RESULTS: Patients with calcification of carotid plaques had fewer symptoms of
      stroke and transient ischemic attack (P=0.042) than those without calcification.
      Stroke and transient ischemic attack occurred less frequently in patients with
      plaques with large calcific granules (P=0.021). Of the patients, 13% had lamellar
      bone formation, which directly correlated with the presence of sheetlike
      calcifications (P=0.0001) and inversely correlated with ulcerated lesions
      (P=0.048). The presence of bone also correlated with diabetes (P<0.01) and
      coronary artery disease (P<0.01). Of the 20 patients with bone, 6 had a history
      of stoke and transient ischemic attack (P=0.5). CONCLUSIONS: The results indicate
      that bone formation tends to occur in heavily calcified carotid lesions devoid of
      ulceration and hemorrhage. Patients with extensive calcification of the carotid
      plaques are less likely to have symptomatic disease.

PMID- 11988594
TI  - Large and deep brain arteriovenous malformations are associated with risk of
      future hemorrhage.
AB  - BACKGROUND AND PURPOSE: The correlation between features present in brain
      arteriovenous malformations (AVMs) such as size, location, and angioarchitecture
      at presentation with subsequent risk of hemorrhage may be valuable in predicting
      the behavior of AVMs and therefore guiding management. METHODS: We prospectively
      followed up 390 patients with brain AVMs at the University of Toronto Vascular
      Malformation Study Group. Location, size, angioarchitecture details, blood
      supply, and clinical presentation were recorded at baseline. Intracranial
      hemorrhages during follow-up were recorded. Significant factors from univariate
      analyses were used to construct a multivariate model relating the above features
      to the occurrence of hemorrhage. RESULTS: Thirty-eight patients had bleeding
      caused by the AVM in a follow-up of 1205 patient-years (mean, 3.1 years per
      patient). In analyses adjusted for multiple AVM characteristics, large AVMs bled
      more frequently than small lesions (odds ratio [OR], 2.5; 95% confidence interval
      [CI], 1.41 to 4.35; P<0.0001), and deep-seated AVMs had more bleeding in follow
      up than those located at superficial sites (OR, 5.56; 95% CI, 2.63 to 12.5;
      P<0.0001). CONCLUSIONS: Deep-seated and large AVMs were significantly more prone
      to hemorrhage during prospective follow-up. The distinction between factors
      associated with hemorrhagic presentation and the natural history risk of
      hemorrhage will be emphasized.

PMID- 11988595
TI  - Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and
      impact on outcome.
AB  - BACKGROUND AND PURPOSE: Cerebral edema visualized by CT is often seen after
      subarachnoid hemorrhage (SAH). Inflammatory or circulatory mechanisms have been
      postulated to explain this radiographic observation after SAH. We sought to
      determine the frequency, causes, and impact on outcome of early and delayed
      global cerebral edema after SAH. METHODS: We evaluated the presence of global
      edema on admission and follow-up CT scans in 374 SAH patients admitted within 5
      days of onset to our Neurological Intensive Care Unit between July 1996 and
      February 2001. Using multivariate analysis, we identified predictors of global
      cerebral edema and evaluated the impact of global edema on outcome 3 months after
      onset with the modified Rankin Scale. RESULTS: Global edema was present on
      admission CT scans in 8% (n=29) and developed secondarily in 12% (n=44) of the
      patients. Global edema on admission was predicted by loss of consciousness at
      ictus and increasing Hunt-Hess grade. Delayed global edema was predicted by
      aneurysm size >10 mm, loss of consciousness at ictus, use of vasopressors, and
      increased SAH sum scores. Thirty-seven percent (n=137) of the patients were dead
      or severely disabled (modified Rankin Scale 4 to 6) at 3 months. Death or severe
      disability was predicted by any global edema, aneurysm size >10 mm, loss of
      consciousness at ictus, increased National Institutes of Health Stroke Scale
      scores, and older age. CONCLUSIONS: Global edema is an independent risk factor
      for mortality and poor outcome after SAH. Loss of consciousness, which may
      reflect ictal cerebral circulatory arrest, is a risk factor for admission global
      edema, and vasopressor-induced hypertension is associated with the development of
      delayed global edema. Critical care management strategies that minimize edema
      formation after SAH may improve outcome.

PMID- 11988596
TI  - Clinical course of cranial dural arteriovenous fistulas with long-term persistent
      cortical venous reflux.
AB  - BACKGROUND AND PURPOSE: The natural history of aggressive (Borden 2 and 3)
      cranial dural arteriovenous fistulas (DAVFs) is not well described. Reported
      annual mortality and hemorrhage rates vary widely and range up to 20% per year. A
      consecutive single-center cohort of 236 cases that presented with a cranial DAVF
      between June 1984 and May 2001 was reviewed for the consequences of long-term
      persistent cortical venous reflux (CVR). METHODS: A group of 118 cranial DAVFs
      was selected for the presence of CVR. All patients were offered treatment aimed
      at the disconnection of the CVR. Patients who declined or had partial treatment
      with persistence of the CVR had long-term clinical and angiographic follow-up to
      study the disease course of this select group. RESULTS: Treatment was instituted
      in 101 of the 118 patients (85.6%). Three patients were lost to follow-up. The
      remaining 14 nontreated patients (11.9%) and the partially treated patients (n=6)
      were assessed clinically and angiographically over time. The mean follow-up in
      this select group was 4.3 years (86.9 patient-years). During follow-up, 7
      patients suffered an intracranial hemorrhage (35%). The incidence of
      nonhemorrhagic neurological deficit was 30%. Nine patients (45%) died: 6 patients
      expired after a hemorrhage, and 3 patients died of progressive neurological
      deterioration. Two patients demonstrated a spontaneous closure of the DAVF (10%).
      CONCLUSIONS: Persistence of the CVR in cranial DAVFs yields an annual mortality
      rate of 10.4%. Excluding events at presentation, in this series the annual risk
      for hemorrhage or nonhemorrhagic neurological deficit during follow-up was 8.1%
      and 6.9%, respectively, resulting in an annual event rate of 15.0%.

PMID- 11988597
TI  - Platelet P-selectin levels in relation to plasma soluble P-selectin and beta
      thromboglobulin levels in atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: The increased risk of stroke and thromboembolism in
      atrial fibrillation (AF) may be related to a prothrombotic or hypercoagulable
      state, with abnormalities of hemostasis and platelet activation. To investigate
      the role of platelets in AF and the influence of antithrombotic therapy, we
      developed and then applied a new assay to detect the absolute amount of P
      selectin per platelet (pP-selectin) based on cell lysis. Thus, pP-selectin in AF
      patients was compared with that of healthy controls and also with plasma soluble
      P-selectin (sP-selectin) and beta-thromboglobulin as established indices of
      platelet activation. METHODSMDSAH: We studied 122 patients (mean [SD] age, 71 [9]
      years; 65 men) with chronic AF of >6 weeks' duration: 34 were not on
      antithrombotic therapy, 30 were taking aspirin (75 to 300 mg/d), and 58 were
      fully anticoagulated with warfarin. pP-selectin was compared with sP-selectin and
      plasma beta-thromboglobulin levels (enzyme-linked immunosorbent assay). Results
      were compared with those of 23 healthy controls (mean [SD] age, 74 [9] years; 7
      men) in sinus rhythm. RESULTS: pP-selectin was significantly lower in AF patients
      on no antithrombotic therapy (P=0.03) than in healthy controls, but sP-selectin
      and beta-thromboglobulin levels were not significantly different and did not
      differ in patients taking aspirin or warfarin. However, pP-selectin was lower in
      patients with AF on aspirin than in those on warfarin (P<0.05). pP-selectin/sP
      selectin correlated significantly in healthy controls (r=0.47, P=0.03) but
      inversely (r=-0.43, P=0.03) in AF patients on no antithrombotic therapy.
      CONCLUSIONS: Lower levels of pP-selectin may represent a depletion of pP-selectin
      after platelet activation in AF. Aspirin further decreases pP-selectin levels
      compared with warfarin. On the basis of the principle of platelet lysis, we
      demonstrate that it is possible to determine the amount of P-selectin per
      platelet, which may be regulated in the megakaryocyte through a cyclooxygenase
      dependent pathway.

PMID- 11988598
TI  - Regional cerebral blood flow and magnetic resonance spectroscopic imaging
      findings in diaschisis from stroke.
AB  - BACKGROUND AND PURPOSE: This study evaluated blood flow and metabolite changes in
      cerebral diaschisis from internal capsule region infarction using regional
      cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) and
      1H magnetic resonance spectroscopic imaging (MRSI). We hypothesized that
      complementary measures of diaschisis effects in white matter (characterized by 1H
      MRSI) and gray matter (characterized by changes in rCBF) can be measured and
      exhibit parallel changes. METHODS: Five stroke patients and 16 normal controls
      underwent Tc-99m hexamethylpropyleneamine-oxime brain SPECT and 1H MRSI at 4.1 T.
      The metabolites N-acetyl aspartate (NAA) and creatine (Cr) were measured using 1H
      MRSI. The tissue content was expressed as the percent of gray or white matter in
      each MRSI voxel to allow comparison of the differential effects of diaschisis in
      gray and white matter tissue types. The blood flow and metabolite changes were
      evaluated at superior cerebral regions distant from the stroke to allow a measure
      of diaschisis relatively unconfounded by their expected changes in the infarction
      region. RESULTS: The rCBF SPECT data in stroke patients showed a perfusion
      defect, with size ranging from 1.23 cc to 10.23 cc, in the region of cortical
      diaschisis. 1H MRSI showed increased Cr/NAA ratios in regions of white matter
      diaschisis. There was a tendency for larger rCBF defect size to be associated
      with greater increases in Cr/NAA values in the same diaschitic cerebral
      hemisphere, ipsilateral to the infarction. CONCLUSION: Diaschisis ipsilateral to
      stroke in white matter can be characterized by 1H MRSI, and diaschisis
      ipsilateral to stroke in cortical gray matter regions can be characterized by
      changes in rCBF. The tendency for greater reductions in cortical rCBF values to
      be associated with increased Cr/NAA values in the same diaschitic cerebral
      hemisphere implies that a relationship exists between rCBF reductions in gray
      matter and abnormal changes in white matter subservient to it.

PMID- 11988599
TI  - Chlamydia pneumoniae serology is associated with thrombosis-related but not with
      plaque-related microembolization during carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Chlamydia pneumoniae has repeatedly been associated with
      atherosclerotic disease. Our study was designed to clarify whether this
      association is based on C pneumoniae-induced transformation of a stable into an
      unstable atherosclerotic plaque or on stimulation of hypercoagulability leading
      to increased thrombotic arterial occlusions by C pneumoniae infection.
      Transcranial Doppler ultrasonographic monitoring of the middle cerebral artery
      during carotid endarterectomy offers the opportunity to study, before removal of
      the plaque, atherothrombotic emboli dislodging from an unstable carotid plaque
      (plaque-related emboli) and emboli related to (excessive) thrombus formation at
      the endarterectomy site after removal of the plaque and restoration of flow
      (thrombosis-related emboli). METHODS: C pneumoniae IgA (> or =1/16) and IgG (> or
      =1/64) seropositivity was assessed in 53 patients with symptomatic carotid artery
      disease undergoing carotid endarterectomy. The removed carotid plaques were
      studied histologically to assess plaque instability. RESULTS: Plaque- and
      thrombosis-related emboli were registered in 43 patients with an adequate
      transtemporal window. IgA seropositivity (58%) was associated significantly with
      thrombosis-related embolization (P=0.030) but not with plaque-related
      embolization or with histological plaque instability. CONCLUSIONS: C pneumoniae
      serology is associated with microembolization after endarterectomy and
      restoration of flow. Since these microemboli represent platelet aggregations and
      are related to cerebrovascular complications, our data suggest that C pneumoniae
      infection contributes to cerebrovascular events in patients with carotid artery
      disease through stimulation of thrombosis.

PMID- 11988600
TI  - Association between carotid intima-media thickness and low-density lipoprotein
      size and susceptibility of low-density lipoprotein to oxidation in asymptomatic
      members of familial combined hyperlipidemia families.
AB  - BACKGROUND AND PURPOSE: In addition to low-density lipoprotein (LDL) cholesterol,
      small, dense LDL particles and oxidative modification of LDL have been linked to
      the pathogenesis of atherosclerosis. The present study was aimed at investigating
      the association between carotid artery intima-media thickness (IMT) and LDL
      particle size and susceptibility of LDL to oxidation in vitro in asymptomatic
      members of familial combined hyperlipidemia (FCHL) families. METHODS: LDL
      particle size, susceptibility of LDL to oxidation in vitro, and carotid IMT were
      measured in 148 asymptomatic FCHL family members. RESULTS: LDL particle size and
      lag time for LDL oxidation were reduced in hyperlipidemic compared with
      normolipidemic family members. LDL particle size, serum total cholesterol, and
      alpha-tocopherol in LDL were independently associated with lag time for LDL
      oxidation in multivariate analysis. LDL particle size was associated with carotid
      mean IMT independently of clinical, lipid, and antioxidant variables in
      multivariate analysis. Although the susceptibility of LDL to oxidation in vitro
      was correlated with mean IMT, it did not have a significant independent
      contribution to variation in mean IMT in the multivariate model. CONCLUSIONS: We
      conclude that LDL particle size but not susceptibility of LDL to oxidation in
      vitro is independently associated with carotid IMT in asymptomatic FCHL family
      members. These results imply that small, dense LDL as an inherent feature of FCHL
      is an important diagnostic indicator for coronary artery disease risk in FCHL.

PMID- 11988601
TI  - Modified National Institutes of Health Stroke Scale for use in stroke clinical
      trials: prospective reliability and validity.
AB  - BACKGROUND AND PURPOSE: To prospectively evaluate the reliability and validity of
      this previously developed stroke scale in an independently collected cohort. The
      National Institutes of Health Stroke Scale (NIHSS) has been criticized for its
      complexity and variability. Prior formal clinimetric analyses were used to obtain
      a modified version of NIHSS (mNIHSS), which retrospectively demonstrated improved
      reliability and validity. We sought to prospectively measure the reliability and
      validity of the mNIHSS. METHODS: Forty-five patients with a history of stroke or
      intracerebral hemorrhage were evaluated at the University of California, San
      Diego, Stroke Center from September 2000 through March 2001. Each patient was
      tested by 2 NIHSS-certified neurologists using the NIHSS, mNIHSS, Barthel Index,
      and Modified Rankin scales. RESULTS: There were a large percentage of high kappa
      values using the mNIHSS. Only 10 (66.67%) of 15 NIHSS kappa scores showed
      excellent agreement, whereas 10 (90.91%) of 11 mNIHSS kappa scores showed
      excellent agreement. As predicted, the mNIHSS was more reliable than the NIHSS
      because of the exclusion of items with low kappa values. With the use of
      correlation coefficient analysis, the mNIHSS was as valid as the NIHSS.
      CONCLUSIONS: This prospective study found high reliability and continued validity
      by using a previously developed mNIHSS. Items found to have low kappa values were
      consistent with the previously derived retrospective mNIHSS. The resulting mNIHSS
      scale has much higher kappa values. The mNIHSS showed improved agreement between
      examiners and was also easier to administer, having fewer and simpler items.
      Further prospective evaluation should assess whether the mNIHSS could be used in
      lieu of the NIHSS.

PMID- 11988602
TI  - Acute ischemic stroke patterns in infective and nonbacterial thrombotic
      endocarditis: a diffusion-weighted magnetic resonance imaging study.
AB  - BACKGROUND AND PURPOSE: Although infective endocarditis (IE) and nonbacterial
      thrombotic endocarditis (NBTE) are associated with cardioembolic stroke,
      differences in the nature of these conditions may result in differences in
      associated stroke patterns. We compared patterns of acute and recurrent ischemic
      stroke in IE and NBTE, using diffusion-weighted MRI (DWI). METHODS: Using ICD-9
      diagnostic codes and medical record review, we identified 362 patients (387
      episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27
      episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were
      selected for this study. DWI lesion size, number, and location were compared
      between groups and correlated with stroke syndromes and endocarditis features.
      RESULTS: DWI was abnormal in all but 2 patients. Four acute stroke patterns were
      identified: (1) single lesion, (2) territorial infarction, (3) disseminated
      punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or
      large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited
      pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9
      episodes, respectively). Seventy-five percent of patients with pattern 3
      exhibited the clinical syndrome of embolic encephalopathy. Vegetation size,
      valve, and organisms had no correlation with stroke patterns. CONCLUSION: DWI has
      utility in differentiating between IE and NBTE. Patients with NBTE uniformly have
      multiple, widely distributed, small and large strokes, whereas patients with IE
      exhibit a panoply of stroke patterns.

PMID- 11988603
TI  - Hemodynamic studies in early ischemic stroke: serial transcranial Doppler and
      magnetic resonance angiography evaluation.
AB  - BACKGROUND AND PURPOSE: After acute stroke, it is often standard practice to
      obtain magnetic resonance angiography (MRA) to seek evidence of a plausible
      stroke mechanism. However, hemodynamic patterns after acute ischemic stroke are
      variable and dynamic. We evaluated information obtained by serial transcranial
      Doppler ultrasonography (TCD) examinations within the first week after acute
      ischemic stroke and compared it with that obtained from a single MRA study.
      METHODS: Forty-seven patients (aged 61+/-7 years) with acute ischemic hemispheric
      stroke were examined. TCD was performed within 24 hours, from 24 to 48 hours, and
      4 to 8 days after ictus. Norms for TCD examination were determined in an age
      matched control group that included 41 subjects without cerebrovascular disease
      (aged 57+/-10 years). RESULTS: In 17 stroke patients, the results of initial TCD
      examination were normal, although TCD follow-up showed gradual deterioration of
      middle cerebral artery (MCA) for 1 patient with normal MRA. In 12 patients,
      initial TCD study and MRA showed MCA or posterior cerebral artery occlusion.
      Serial TCD examinations documented recanalization (6 patients), formation of a
      residual MCA stenosis (1 patient), or progressive deterioration of flow through a
      symptomatic MCA (1 patient), not evident on MRA. In 5 patients MRA was normal,
      but early TCD demonstrated signs of previous recanalization (transitory
      hyperemia, slow flow restoration). In 2 patients with MCA branch occlusion, MRA
      suggested occlusion but failed to document either improvement (1 patient) or
      deterioration (1 patient) of flow that was evident with serial TCD. In 4 patients
      with proximal MCA stenosis and 5 patients with internal carotid artery occlusion
      or stenosis, serial TCD demonstrated different patterns of collateralization and
      suggested dynamic collateralization patterns after stroke that were not evident
      on MRA. CONCLUSIONS: Serial TCD examination may reveal dynamic changes in
      cerebral circulation that may be missed on a single MRA study.

PMID- 11988604
TI  - Magnetic resonance angiography in childhood arterial brain infarcts: a
      comparative study with contrast angiography.
AB  - BACKGROUND AND PURPOSE: Contrast angiography (CA) is the reference examination
      for the diagnosis of cerebral arterial abnormality, but this procedure is
      invasive. In childhood, ischemic strokes are being increasingly investigated by
      means of MRI, including MR angiography (MRA). Very few data are available about
      the accuracy of MRA compared with CA in the specific context of acute pediatric
      stroke. We sought to compare the results of MRA with those of CA for the study of
      cerebral arteries in children with arterial infarction in an arterial
      distribution. METHODS: Twenty-four children presenting with 26 infarcts were
      studied. All were examined with cerebral MRI and MRA and with CA. The interval
      between CA and MRA was <3 days for most of the patients. RESULTS: Arterial
      lesions were detected in all but 2 children. They were located in the major
      cerebral arteries, predominantly in the anterior circulation (85% of cases). All
      lesions shown by CA were present on MRA (19 cases). Patients with no lesion on
      MRA had normal CA (2 cases). Associated distal vascular lesions and degree of
      arterial stenosis were more accurately detected with CA. CONCLUSIONS: MRA is
      sensitive enough to provide an adequate initial evaluation of arterial brain
      disease in childhood.

PMID- 11988605
TI  - Brain representation of hemifield stimulation in poststroke visual field defects.
AB  - BACKGROUND AND PURPOSE: Plasticity in extended, parallel, or reciprocal operating
      networks is well recognized. Changes in neuronal activity after lesions to
      distinct localized structures, such as the primary visual cortex, are less well
      characterized. We investigated the cortical reorganization in patients with
      poststroke visual field defects using blood oxygen level-dependent functional
      MRI. METHODS: Brain activation was measured in 7 patients with a single occipital
      cortical lesion and partially recovered hemianopia and in 7 age-matched control
      subjects. Differences in activation between rest and visual hemifield stimulation
      were assessed with statistical parametric mapping (SPM'99). RESULTS: In normal
      subjects, significant activation was found in the contralateral primary visual
      cortex and bilaterally in the extrastriate cortex. During hemifield stimulation
      of the unaffected side of stroke patients, a similar pattern was found compared
      with that seen in control subjects. During stimulation of the hemianopic side,
      bilateral activation was seen within the extrastriate cortex, stronger in the
      ipsilateral hemisphere. The primary visual cortex was not significantly activated
      in either hemisphere during stimulation of the hemianopic side. CONCLUSIONS:
      Visual field defects after stroke are associated with bilateral activation of the
      extrastriate visual cortex. This pattern of activation indicates altered neuronal
      activity in the visual system. Further investigation is necessary to determine
      the relationship between functional reorganization and recovery of lost visual
      function after poststroke hemianopia.

PMID- 11988606
TI  - Changes in blood flow and oxygen metabolism during visual stimulation in carotid
      artery disease: effect of baseline perfusion and oxygen metabolism.
AB  - BACKGROUND AND PURPOSE: Severe atherosclerotic disease of the carotid arteries
      may affect perfusion in the posterior circulation according to the degree of
      collateral supply. The purpose of this study was to determine whether the
      responses of regional cerebral blood flow (rCBF) and regional cerebral metabolic
      rate of oxygen (rCMRO2) during neural stimulation are affected by the baseline
      perfusion or oxygen metabolism. METHODS: We used PET to measure rCBF, rCMRO2, and
      regional oxygen extraction fraction (rOEF) in 13 patients with carotid artery
      steno-occlusive lesions at baseline and during visual stimulation. We examined
      whether the changes in CBF, CMRO2, and OEF during visual stimulation were
      correlated with the baseline values of these parameters in the visual cortex.
      RESULTS: With visual stimulation, rCBF increased in all patients, whereas rCMRO2
      showed variable changes. The baseline rCMRO2 value showed a positive relationship
      with the degree of rCBF increase and a negative relationship to the degree of
      rCMRO2 increase. rCMRO2 decreased in patients with relatively high baseline
      rCMRO2 values, resulting in dissociation of the rCMRO2 response from the rCBF
      response. The rCBF increase was large in the region with an increased baseline
      rOEF value. These variable changes in rCBF and rCMRO2 resulted in a significant
      correlation between the values of rCBF and rCMRO2 during visual stimulation in
      contrast to the lack of such a correlation at baseline. CONCLUSIONS: In patients
      with cerebrovascular disease, neural stimulation may induce variable changes in
      rCBF and rCMRO2 according to the baseline perfusion and oxygen metabolism.

PMID- 11988607
TI  - Early dramatic recovery during intravenous tissue plasminogen activator infusion:
      clinical pattern and outcome in acute middle cerebral artery stroke.
AB  - BACKGROUND AND PURPOSE: Acute-stroke patients receiving standard intravenous
      tissue plasminogen activator (tPA) have been noted to experience early dramatic
      recoveries. The prevalence, clinical characteristics, and outcome of patients
      experiencing dramatic recovery is not well described. METHODS: We prospectively
      studied all patients presenting with acute middle cerebral artery (MCA) stroke
      syndromes and transcranial Doppler (TCD) evidence of an MCA obstruction. All
      patients received intravenous tPA per the National Institute of Neurological and
      Communicative Disorders and Stroke protocol, with serial National Institutes of
      Health Stroke Scale (NIHSS) scores and continuous TCD monitoring. Dramatic
      recovery was defined as an improvement of > or =10 NIHSS points or a decrease to
      an NIHSS score of < or =3 by the end of infusion. Outcome at the end of infusion,
      at 24 hours, and at long-term follow-up were obtained. The timing and pattern of
      deficit recovery during dramatic recovery was also studied. RESULTS: Dramatic
      recovery occurred in 22% of all patients. Compared with patients who did not
      experience dramatic recovery, those patients who did had significantly lower end
      infusion NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus
      median 17 and range 6 to 35 for non-dramatic-recovery patients, P<0.01) and 24
      hour NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus
      median 13 and range 2 to 35 for non-dramatic-recovery patients, P<0.01). A long
      term modified Rankin Score benefit was noted (median 1 and range 0 to 6 for
      dramatic-recovery patients versus median 4 and range 0 to 6 for non-dramatic
      recovery patients, P<0.01). Baseline clinical characteristics were similar. The
      only difference was improved TCD-determined flow values at the end of infusion
      (normal restoration of flow was 58% in dramatic-recovery patients versus 14% in
      non-dramatic-recovery patients, P<0.01). A characteristic pattern of recovery of
      deficit was noted. CONCLUSIONS: Early dramatic recovery in acute MCA stroke
      patients treated with intravenous tPA is relatively frequent. The benefit of
      dramatic recovery is maintained at 24 hours and over the long term. TCD
      monitoring suggests that dramatic recovery is a result of early restoration of
      MCA flow during the tPA infusion. The consistent pattern of early clinical
      recovery may help explain the mechanisms by which thrombolysis improves outcome
      and could suggest targets for enhancing the therapeutic effect of intravenous
      tPA.

PMID- 11988608
TI  - Carotid artery stenting protected with an emboli containment system.
AB  - BACKGROUND AND PURPOSE: Fear of distal embolization and stroke has aroused
      concern regarding carotid stenting. Devices to protect the cerebral circulation
      may make carotid stenting safer. METHODS: A multidisciplinary study group tested
      a balloon occlusion-aspiration emboli entrapment device in conjunction with
      carotid stenting. The device consists of an elastomeric balloon on a steerable
      wire with a detachable adapter that inflates and deflates the distal temporary
      occlusion balloon. An aspiration catheter is used to remove trapped emboli after
      stenting and before occlusion balloon deflation. RESULTS: Seventy-five patients
      with severe internal carotid artery stenosis were treated with stents deployed
      with this cerebrovasculature protection system. All 75 patients (100%) had
      grossly visible particulate material aspirated, and all were treated successfully
      without major or minor stroke or death at 30 days. Preintervention stenosis was
      81+/-10%, and residual stenosis was 5+/-7%. Nine patients (12%) had angiographic
      evidence of thrombus before intervention, but no patient had thrombus or vessel
      cutoff after the procedure. Four patients (5%) developed transient neurological
      symptoms during protection balloon occlusion, but symptoms resolved with balloon
      deflation. The 22 to 667 particles aspirated per patient ranged from 3.6 to 5262
      microm in maximum diameter (mean, 203+/-256 microm). These particles included
      fibrous plaque debris, lipid or cholesterol vacuoles, and calcific plaque
      fragments. CONCLUSIONS: Protected carotid stenting was performed successfully and
      safely in this study early in the experience with cerebrovascular protection
      devices. Particulate emboli are frequent with stenting, and cerebral protection
      will likely be necessary to minimize stroke. Randomized trials comparing
      protected carotid stenting with endarterectomy are warranted.

PMID- 11988609
TI  - Blood pressure and clinical outcomes in the International Stroke Trial.
AB  - BACKGROUND AND PURPOSE: Among patients with acute stroke, high blood pressure is
      often associated with poor outcome, although the reason is unclear. We analyzed
      data from the International Stroke Trial (IST) to explore the relationship
      between systolic blood pressure (SBP), subsequent clinical events over the next 2
      weeks, and functional outcome at 6 months in patients with acute stroke. METHODS:
      We included in the analysis 17 398 patients from IST with confirmed ischemic
      stroke. A single measurement of SBP was made immediately before randomization.
      Clinical events within 14 days of randomization were recorded: recurrent ischemic
      stroke, symptomatic intracranial hemorrhage, death resulting from presumed
      cerebral edema, fatal coronary heart disease, and death. Survival and dependency
      were assessed at 6 months. Outcomes were adjusted for age, sex, clinical stroke
      syndrome, time to randomization, consciousness level, atrial fibrillation, and
      treatment allocation (aspirin, unfractionated heparin, both, or neither).
      RESULTS: A U-shaped relationship was found between baseline SBP and both early
      death and late death or dependency: early death increased by 17.9% for every 10
      mm Hg below 150 mm Hg (P<0.0001) and by 3.8% for every 10 mm Hg above 150 mm Hg
      (P=0.016). The rate of recurrent ischemic stroke within 14 days increased by 4.2%
      for every 10-mm Hg increase in SBP (P=0.023); this association was present in
      both fatal and nonfatal recurrence. Death resulting from presumed cerebral edema
      was independently associated with high SBP (P=0.004). No relationship between
      symptomatic intracranial hemorrhage and SBP was seen. Low SBP was associated with
      a severe clinical stroke (total anterior circulation syndrome) and an excess of
      deaths from coronary heart disease (P=0.002). CONCLUSIONS: Both high blood
      pressure and low blood pressure were independent prognostic factors for poor
      outcome, relationships that appear to be mediated in part by increased rates of
      early recurrence and death resulting from presumed cerebral edema in patients
      with high blood pressure and increased coronary heart disease events in those
      with low blood pressure. The occurrence of symptomatic intracranial hemorrhage
      within 14 days was independent of SBP.

PMID- 11988610
TI  - Subarachnoid hemorrhage: a preventable disease with a heritable component.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) caused by ruptured
      intracranial aneurysm affects approximately 16 000 Americans annually, and almost
      40% of affected patients die within 30 days despite the best current therapy.
      Prevention of SAH is therefore of paramount importance. We present a preliminary
      analysis of risk factors for SAH from our population-based, case-control study.
      METHODS: Cases were prospectively collected and matched 2:1 by age, race, and
      gender to controls using random digit dialing. Personal risk factor history,
      family history, neuroimaging data, and genetic samples were obtained. Univariate
      and bivariate analyses were performed and population-attributable risks
      estimated. Multivariable analysis was performed using conditional logistic
      regression. RESULTS: Between June 1997 and February 2000, 107 cases and 197
      controls were enrolled. In bivariate analyses, a large proportion of population
      attributable risk for SAH could be explained by modifiable risk factors: smoking,
      hypertension, and heavy alcohol use. In multivariable analysis, current cigarette
      smoking, history of hypertension, frequent alcohol use, lower body mass index,
      and a family history of a relative with SAH or intracranial aneurysm were found
      to be significant, independent risk factors for SAH. CONCLUSION: Our data confirm
      previous reports that SAH clusters within some families independent of
      environmental risk factors, suggesting that SAH has a significant genetic
      component. Yet, even among families at increased risk of SAH, smoking cessation,
      treatment of hypertension, and reduced alcohol intake may substantially decrease
      SAH risk. The independent associations with heavy alcohol use and low body mass
      index with SAH may be confounded by smoking and require further study.

PMID- 11988611
TI  - Poststroke fatigue: a 2-year follow-up study of stroke patients in Sweden.
AB  - BACKGROUND AND PURPOSE: Fatigue is common among stroke patients. This study
      determined the prevalence of fatigue among long-term survivors after stroke and
      what impact fatigue had on various aspects of daily life and on survival.
      METHODS: This study was based on Riks-Stroke, a hospital-based national register
      for quality assessment of acute stroke events in Sweden. During the first 6
      months of 1997, 8194 patients were registered in Riks-Stroke, and 5189 were still
      alive 2 years after the stroke. They were followed up by a mail questionnaire, to
      which 4023 (79%) responded. Patients who reported that they always felt depressed
      were excluded. RESULTS: To the question, "Do you feel tired?" 366 (10.0%) of the
      patients answered that they always felt tired, and an additional 1070 (29.2%)
      were often tired. Patients who always felt tired were on average older than the
      rest of the study population (74.5 versus 71.5 years, P<0.001); therefore, all
      subsequent analyses were age adjusted. Fatigue was an independent predictor for
      having to move into an institutional setting after stroke. Fatigue was also an
      independent predictor for being dependent in primary activities of daily living
      functions. Three years after stroke, patients with fatigue also had a higher case
      fatality rate. CONCLUSIONS: Fatigue is frequent and often severe, even late after
      stroke. It is associated with profound deterioration of several aspects of
      everyday life and with higher case fatality, but it usually receives little
      attention by healthcare professionals. Intervention studies are needed.

PMID- 11988612
TI  - Acute stroke care in Illinois: a statewide assessment of diagnostic and treatment
      capabilities.
AB  - BACKGROUND AND PURPOSE: To define areas for quality improvement in acute stroke
      care, a statewide assessment of preparedness for acute stroke diagnosis and
      treatment was carried out among 202 acute receiving hospitals in Illinois.
      METHODS: Medical directors or their designees completed a 1-page survey form that
      addressed availability of personnel, diagnostic technology, and organized
      programs for the treatment of acute stroke patients at their facility. In the
      analysis, acute care receiving hospitals in the Greater Chicago Metropolitan Area
      (GCMA) (Cook, Dupage, Lake, Will, and Kane counties) were compared with those in
      the remainder of the state. RESULTS: Of the acute care receiving hospitals, 91%
      responded to the survey. Overall, 99% had an emergency room receiving facility,
      98.3% had a CT scanner, and slightly >70% had a recombinant tissue plasminogen
      activator (r-TPA) protocol. We found that 93.2% of residents in Illinois lived in
      a county with at least 1 acute care facility with an r-TPA treatment protocol.
      However, many of the non-GCMA receiving hospitals did not have a neurologist or a
      neurosurgeon available. Furthermore, specialized stroke diagnostic technology
      (eg, transcranial Doppler, diffusion-weighted MRI, MR angiography) was generally
      lacking in both the GCMA and non-GCMA, as were stroke community awareness
      programs and acute care stroke teams. CONCLUSIONS: Stroke is a preventable and
      treatable disease. However, there are barriers to stroke care that are based on
      the availability of personnel, diagnostic technology, and programs. A systematic
      approach to the organization, implementation, and maintenance of services could
      improve outcome for stroke patients and reduce the public health burden of this
      deadly disease.

PMID- 11988613
TI  - Guideline compliance improves stroke outcome: a preliminary study in 4 districts
      in the Italian region of Lombardia.
AB  - BACKGROUND AND PURPOSE: Guidelines for medical practice in stroke have been
      proposed in different countries, but their impact on stroke outcome has not been
      verified to date. The aim of this study was to evaluate the impact of the
      American Heart Association guidelines for acute stroke and for transient ischemic
      attack on first-ever stroke patients. METHODS: Three hundred eighty-six first
      ever ischemic stroke patients were admitted to the study. Those observed within 6
      hours from stroke onset were eligible for the acute clinical phase of the study,
      while all were admitted to the early clinical phase. The follow-up lasted 6
      months. Primary end points were survival and the effectiveness of treatment on
      disability, measured as the proportion of potential improvement in the Barthel
      Index score achieved during treatment. A rating of noncompliance with the
      guideline recommendations was calculated for each patient, and its association
      with the end points was investigated. The Kaplan-Meier method and log-rank test
      were used to estimate and compare survival curves between groups; Cox
      proportional hazards model and logistic regression were used to identify risk
      factors for mortality; and correlation tests and regression analysis were used to
      evaluate the influence of guideline compliance on disability. Both univariate and
      multivariate statistical analyses were performed. RESULTS: Survival and treatment
      effectiveness were directly correlated with guideline compliance. The relative
      risk of death for patients with a noncompliance rating > or =5 was 2.26 with
      respect to patients with a noncompliance rating <5 (95% CI, 1.51 to 4.67;
      P<0.0007). In this latter group, at 6 months we detected a 15% decrease in
      mortality (95% CI, 9.1% to 17.5%). Treatment effectiveness showed a Spearman's
      rank correlation with the noncompliance rating of -0.3 (P<0.001). At discharge we
      observed a 13% increase in treatment effectiveness, while no significant
      differences were detectable at 3 and 6 months. These associations were confirmed
      by the multivariate analysis, in which we included, together with the
      noncompliance rating, all the variables previously identified as independent
      predictors of mortality and disability. CONCLUSIONS: This study demonstrates an
      association between adherence to guidelines and stroke outcome, and it can be
      viewed as a study that prepares the way for a randomized controlled trial in this
      area. It also emphasizes the need to develop personnel and structures devoted to
      stroke care because an evidence-based clinical approach could significantly
      reduce the risk of death.

PMID- 11988614
TI  - Quality of life measurement after stroke: uses and abuses of the SF-36.
AB  - BACKGROUND AND PURPOSE: The Medical Outcomes Study 36-item Short-Form Health
      Survey (SF-36) is widely used to measure health status after stroke. However, a
      fundamental assumption for its valid use after stroke has not been
      comprehensively tested: is it legitimate to generate scores for 8 scales and 2
      summary measures using the standard algorithms? We tested this assumption.
      METHODS: SF-36 data from 177 people after stroke were examined (71% male; mean
      age, 62). We tested 6 scaling criteria to determine the legitimacy of generating
      the 8 SF-36 scale scores using Likert's method of summed ratings, and we tested 2
      scaling criteria to determine the appropriateness of the standard SF-36
      algorithms for weighting and combining scale scores to generate 2 summary
      measures (physical and mental). RESULTS: Scaling assumptions were fully satisfied
      for 6 of the 8 scales, but 3 of these 6 scales had notable floor and/or ceiling
      effects. Assumptions for generating 2 SF-36 summary measures were not satisfied.
      CONCLUSIONS: In this sample, 5 of the 8 SF-36 scales had limited validity as
      outcome measures after stroke, and the reporting of physical and mental summary
      scores was not supported. Results raise questions about the use of the SF-36 in
      stroke, and the SF-12 that is developed from it, and highlight the importance of
      testing scaling assumptions when applying existing scales to new populations.

PMID- 11988615
TI  - Influence of apolipoprotein E, smoking, and alcohol intake on carotid
      atherosclerosis: National Heart, Lung, and Blood Institute Family Heart Study.
AB  - BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) isoforms and lifestyle factors
      play an important role in the development of coronary heart disease. The
      association of apoE and carotid atherosclerosis remains controversial. METHODS:
      We investigated the relation of apoE, cigarette smoking, alcohol drinking, and
      their interaction with carotid atherosclerosis on 544 individuals free of
      coronary heart disease in the National Heart, Lung, and Blood Institute (NHLBI)
      Family Heart Study. Atherosclerotic lesions of the carotid arteries were detected
      through high-resolution ultrasound. RESULTS: Subjects in the apoE4 group had
      lower blood pressure, lower high-density lipoprotein cholesterol, and higher low
      density lipoprotein cholesterol. In a multivariate logistic regression model,
      apoE isoforms and alcohol consumption were not significantly associated with the
      prevalence odds of carotid atherosclerosis (P=0.94 and 0.98, respectively, for
      trend). In contrast, compared with those who never smoked, the prevalence odds
      ratios for carotid atherosclerosis were 1.7 [95% confidence interval (CI),1.1 to
      2.7], 2.8 (95% CI, 1.2 to 6.2), and 1.9 (95% CI, 0.7 to 5.5) for former smokers,
      current smokers of 1 to 20 cigarettes per day, and current smokers of >20
      cigarettes day, respectively (P=0.0018 for trend). We did not find evidence of an
      interaction between apoE and alcohol consumption. Our data suggested a
      synergistic effect between the apoE allele epsilon(4) and smoking on carotid
      atherosclerosis: odds ratios were 1.7 (95% CI, 0.8 to 3.6) for smoking alone, 1.0
      (95% CI, 0.6 to 1.8) for epsilon4 alone, and 3.7 (95% CI, 1.1 to 3.6) for the
      joint presence of the apoE allele epsilon4 and smoking. CONCLUSIONS: Smoking but
      not alcohol consumption or ApoE is associated with an increased odds of carotid
      atherosclerosis. Our data suggest a synergistic effect between the apoE allele
      epsilon4 and smoking on carotid atherosclerosis.

PMID- 11988616
TI  - Bone marrow as a source of endothelial cells and NeuN-expressing cells After
      stroke.
AB  - BACKGROUND AND PURPOSE: After an ischemic event, bone marrow-derived cells may be
      involved in reparative processes. There is increasing evidence that bone marrow
      derived stem cells may be a source of endothelial cells and organ-specific cells.
      Our objectives were to determine whether bone marrow-derived cells were a source
      of endothelial cells and neurons after cerebral ischemia. METHODS: We
      transplanted bone marrow from male C57 BL/6-TgN (ACTbEGFP)1Osb mice, which
      express green fluorescent protein (GFP), into female C57 BL/6J mice. The
      recipient mice then underwent suture occlusion of the middle cerebral artery
      (MCA), and bone marrow- derived cells were tracked by GFP epifluorescence and Y
      chromosome probe. RESULTS: Within 3 days and at 7 and 14 days after MCA
      occlusion, bone marrow-derived cells incorporated into the vasculature in the
      ischemic zone and expressed an endothelial cell phenotype. Few bone marrow
      derived cells incorporated into the vasculature 24 hours after MCA occlusion.
      Some bone marrow-derived cells also expressed the neuronal marker NeuN at 7 and
      14 days after ischemia. CONCLUSIONS: Postnatal vasculogenesis occurs in the brain
      in the setting of a cerebral infarction. Bone marrow-derived cells are a source
      of endothelial cells and NeuN-expressing cells after cerebral infarction. This
      plasticity may be exploited in the future to enhance recovery after stroke.

PMID- 11988617
TI  - Persistent defect in transmitter release and synapsin phosphorylation in cerebral
      cortex after transient moderate ischemic injury.
AB  - BACKGROUND AND PURPOSE: Synaptic transmission is highly vulnerable to metabolic
      perturbations. However, the long-term consequences of transient metabolic
      perturbations on synapses are not clear. We studied the long-lasting changes in
      synaptic transmission and phosphorylation of presynaptic proteins in penumbral
      cortical neurons after transient moderate ischemia. METHODS: Rats were subjected
      to 1 hour of middle cerebral artery occlusion. After reperfusion, electric
      activity of neurons in the peri-infarct region was recorded intracellularly and
      extracellularly in situ. Phosphorylation of synapsin-I and tyrosine residues was
      studied by immunohistochemistry. RESULTS: Neurons in the penumbra displayed no
      postsynaptic potentials 1 to 3 hours after recirculation. However, these cells
      were able to generate action potentials and were responsive to glutamate,
      suggesting that postsynaptic excitability was preserved but the synaptic
      transmission was blocked because of a presynaptic defect. The synaptic
      transmission was still depressed 24 hours after recirculation in neurons in the
      peri-infarct area that survived ischemia. The amount of immunoreactive synapsin
      I, synaptophysin, and synaptotagmin was not appreciably changed for 72 hours
      after reperfusion. However, phosphorylation of synapsin-l was significantly
      decreased, whereas phosphotyrosine immunoreactivity was increased, suggesting a
      selective defect in synapsin-I phosphorylation. CONCLUSIONS: These data
      demonstrate that synaptic transmission may be permanently impaired after
      transient moderate brain injury. Since postsynaptic excitability is preserved,
      the transmission failure is likely to be caused by presynaptic mechanisms, one of
      which may be impaired phosphorylation of presynaptic proteins.

PMID- 11988618
TI  - Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody
      for vector tethering.
AB  - BACKGROUND AND PURPOSE: Endovascular microcoils are widely used in interventional
      procedures to treat cerebral aneurysms. In the present study we report for the
      first time successful use of an endovascular microcoil as a gene delivery system.
      METHODS: Anti-adenoviral monoclonal antibodies were covalently attached to the
      collagen-coated surface of either platinum or polyglycolic acid microcoils. These
      antibodies were used to tether replication-deficient adenovirus (Ad-GFP [encoding
      green fluorescent protein] or Ad-LacZ [encoding beta-galactosidase]). Cell
      culture studies with rat arterial smooth muscle cells (A10) assessed transduction
      on or near the coil. Platinum coils coated with Ad-GFP were implanted into the
      ligated common carotid artery (CCA) of adult rats in a model of arterial stasis
      and pressurization. After 7 days, CCA segments were harvested, and coils were
      removed for histopathology and GFP expression studies, while organs were
      evaluated by polymerase chain reaction to assess viral biodistribution. RESULTS:
      In cell culture studies, GFP-positive smooth muscle cells were detected only on
      the platinum coil surface, while LacZ-positive cells were detected only on the
      polyglycolic acid coil surface, thus demonstrating localized gene delivery. After
      7-day implantation, GFP (according to fluorescence microscopy and confirmed with
      immunohistochemistry) was detected on the harvested platinum coil and in the
      organizing thrombus within the CCA but not in the arterial wall. Morphometric
      analyses revealed that 13.3+2.0% of cells within the organized thrombus were
      transduced with Ad-GFP via the gene delivery system. However, arterial smooth
      muscle cells were negative for GFP according to fluorescence microscopy and
      immunohistochemistry. Ad-GFP was not detectable by polymerase chain reaction in
      lung, liver, or kidney. CONCLUSIONS: It is concluded that catheter deployment of
      platinum or biodegradable gene delivery endovascular microcoils represents an
      interventional device-based gene therapy system that can serve as a suitable
      platform for either single or multiple gene therapy vectors.

PMID- 11988619
TI  - Malignant infarction in cats after prolonged middle cerebral artery occlusion:
      glutamate elevation related to decrease of cerebral perfusion pressure.
AB  - BACKGROUND AND PURPOSE: To study the putative role and predictive significance of
      glutamate elevation in space-occupying ischemic stroke, we investigated the
      correlation between perfusional disturbances and glutamate alterations in a
      transient ischemia model in cats that is susceptible to secondary deterioration
      after reperfusion. METHODS: In 10 halothane-anesthetized cats, the left middle
      cerebral artery was occluded for 3 hours, followed by 6 hours of reperfusion.
      Laser-Doppler flowmetry (LDF) probes, microdialysis/high-performance liquid
      chromatography, and pressure sensors measured simultaneously regional cerebral
      blood flow (CBF), extracellular amino acids, mean arterial blood pressure, and
      intracranial pressure, respectively. Cerebral perfusion pressure (CPP) was
      calculated. In complementary experiments (n=2), regional CBF was assessed by
      sequential positron emission tomography. RESULTS: Middle cerebral artery
      occlusion reduced LDF-measured CBF in all animals to <25% of control. In 5 of 10
      cats, glutamate rose approximately 30-fold during ischemia. LDF-measured CBF and
      glutamate primarily recovered after reperfusion. Glutamate rose again in the late
      reperfusion phase, when CPP decreased to <60 mm Hg, and symptoms of
      transtentorial herniation were recognized. Positron emission tomography revealed
      ischemic thresholds of 15 to 20 mL/100 g per minute for secondary deterioration.
      In the other 5 cats, ischemic elevation of glutamate was significantly smaller,
      and signs of secondary deterioration were not recognized. CONCLUSIONS: Glutamate
      determinations during ischemia predict fatal outcome, as do intracranial pressure
      and CPP measurements during early reperfusion. Secondary amino acid elevation
      during reperfusion is presumably caused by a drastic decrease of CPP to <50 mm Hg
      in the final stage of space-occupying, malignant focal ischemia. At this stage, a
      further progression of injury due to increased glutamate may be irrelevant with
      respect to fatal outcome.

PMID- 11988620
TI  - Prediction of hemorrhagic transformation after thrombolytic therapy of clot
      embolism: an MRI investigation in rat brain.
AB  - BACKGROUND AND PURPOSE: Thrombolytic treatment of stroke carries the risk of
      hemorrhagic transformation. Therefore, the potential of MRI for prediction of
      recombinant tissue plasminogen activator (rtPA)-induced bleeding is explored to
      identify patients in whom rtPA treatment may provoke such complications. METHODS:
      Spontaneously hypertensive rats (SHR) (n=9) were submitted to middle cerebral
      artery (MCA) clot embolism, followed 3 hours later by intra-arterial infusion of
      10 mg/kg rtPA. Untreated SHR (n=9) were infused with saline. MRI imaging was
      performed before treatment and included apparent diffusion coefficient (ADC), T2,
      and perfusion mapping and contrast enhancement with gadolinium-DTPA. The
      distribution of intracerebral hemorrhages was studied 3 days later by
      histological staining. RESULTS: Clot embolism led to the rapid decline of ADC in
      the territory of the occluded artery. Tissue lesion volume derived from ADC
      imaging increased by 155+/-69% in the untreated animals and by 168+/-87% in the
      treated animals (P=NS), determined on the histological sections after 3 days.
      This same lesion growth in both groups indicated absence of therapeutic effect
      after 3-hour treatment delay. Hemorrhagic transformations were significantly more
      frequent in treated SHR (P<0.05). In untreated rats, hemorrhages were found in
      the border zone of the ischemic territory; in treated animals, hemorrhagic
      transformations occurred in the ischemic core region. rtPA-induced hemorrhages
      were predicted by a disturbance of the blood-brain barrier in 3 of 4 animals
      before treatment by Gd-DTPA contrast enhancement but not by ADC, T2, or perfusion
      imaging. The region of contrast enhancement colocalized with subsequent bleeding
      in these animals. CONCLUSIONS: The disturbance of blood-brain barrier but not of
      other MR parameters allows risk assessment for hemorrhagic transformation induced
      by subsequent thrombolytic treatment.

PMID- 11988621
TI  - Can transcranial ultrasonication increase recanalization flow with tissue
      plasminogen activator?
AB  - BACKGROUND AND PURPOSE: In thrombolytic therapy for acute ischemic stroke, it is
      essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To
      develop a new technique of thrombolysis for acute ischemic stroke, the effect of
      transcranially applied ultrasound (TUS) on thrombolysis was examined. METHODS: An
      occlusion model of rabbit femoral artery was produced with thrombin after
      establishment of stenotic flow and endothelial damage. After stable occlusion was
      confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490
      kHz, 0.13 W/cm2) was applied through a piece of temporal bone (TUS group; n=9).
      The control group received mtPA alone (tissue plasminogen activator [tPA] group;
      n=12). To verify the efficacy of TUS, femoral artery flow was measured during the
      procedure. RESULTS: The recanalization ratio was 16.7% (2 of 12) in the tPA group
      and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group
      was higher than that in the tPA group (P=0.03). Patency flow ratio, which was
      defined as recanalization flow divided by baseline flow, of the TUS group (44.6+/
      13.9%) was significantly greater than that of the tPA group (9.9+/-6.8%) at 60
      minutes (P=0.025). Patency flow ratio became higher in the TUS group than in the
      tPA group between 20 and 30 minutes from the start of thrombolysis. CONCLUSIONS:
      Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit
      femoral artery occlusion model. This technique should be clinically useful for
      thrombolysis in acute ischemic stroke.

PMID- 11988622
TI  - MRI evaluation and functional assessment of brain injury after hypoxic ischemia
      in neonatal mice.
AB  - BACKGROUND AND PURPOSE: Severe perinatal asphyxia is an important cause of brain
      injury in the newborn infant. We examined early events after hypoxic ischemia
      (HI) in the 7-day-old mouse brain by MRI and related them to long-term functional
      effects and histopathology in the same animals at 4 to 5 weeks of age. METHODS:
      HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes
      after occlusion of the left common carotid artery. The resulting unilateral focal
      lesion was evaluated in vivo by MRI (T2 maps and apparent diffusion coefficient
      maps) at 3, 6, and 24 hours and 5 days after hypoxia. Locomotion and sensorimotor
      function were analyzed after 3 weeks. Four weeks after HI, the mice were killed,
      and cresyl violet-stained brain sections were examined morphologically. RESULTS:
      A decrease in apparent diffusion coefficient values in cortex on the affected
      side was found at 3 hours after HI. T2 values were significantly increased after
      6 hours and remained so for 5 days. Maximal size of the lesion was attained at 3
      to 6 hours after HI and declined thereafter. Animals with MRI-detected lesions
      had decreased forward locomotion, performed worse than controls in the beam
      walking test, and showed a unilateral hypotrophy in the cresyl violet-stained
      brain sections 4 weeks later. CONCLUSIONS: The temporal progression of the damage
      after HI in 7-day-old mice differs from that of the adult brain as judged by MRI.
      The early lesions detected by MRI were related to functional impairments for
      these mice in near-adult life.

PMID- 11988623
TI  - Neuroprotective effects of the spin trap agent disodium-[(tert
      butylimino)methyl]benzene-1,3-disulfonate N-oxide (generic NXY-059) in a rabbit
      small clot embolic stroke model: combination studies with the thrombolytic tissue
      plasminogen activator.
AB  - BACKGROUND AND PURPOSE: It has been proposed that the novel spin trap agent
      disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) may
      be useful in the treatment of ischemic stroke. However, there is little
      information concerning the neuroprotective properties of NXY-059 when
      administered after an embolic stroke. Moreover, there is no information available
      concerning the combination of NXY-059 with the only Food and Drug Administration
      approved pharmacological agent for the treatment of acute stroke, the
      thrombolytic tissue plasminogen activator (tPA). Thus, we determined the effects
      of NXY-059G, a generic form of NXY-059, on behavioral outcome after an embolic
      stroke when administered alone or in combination with tPA. METHODS: Male New
      Zealand White rabbits were embolized by injecting a suspension of small blood
      clots into cerebral circulation via a carotid catheter. NXY-059G (100 mg/kg) was
      infused intravenously 5 minutes or 3 hours after embolization, whereas control
      rabbits received infusions of the saline vehicle. In tPA studies, the
      thrombolytic was administered intravenously starting 60 minutes or 3 hours after
      embolization (3.3 mg/kg). In combination studies, NXY-059G was given 5 minutes
      after embolization, followed by the administration of tPA beginning either 60
      minutes or 3 hours after embolization. Behavioral analysis was conducted 24 hours
      after embolization. RESULTS: In the vehicle control group, the ES50 value
      (calculated as the amount of microclots [milligrams] that produce neurological
      dysfunction [impairment] in 50% of the rabbits within a specific treatment group)
      measured 24 hours after embolism was 1.04+/-0.31 mg, and this was increased by
      153% to 2.54+/-0.72 mg if NXY-059G was administered beginning 5 minutes after
      embolization. However, if NXY-059G was administered beginning 3 hours after
      embolization, the ES50 was 2.01+/-0.40 mg. The rabbits treated with tPA alone had
      an ES50 of 2.64+/-0.66 or 0.63+/-0.35 mg if tPA administration started 60 minutes
      or 3 hours after embolization, respectively. If tPA was administered after NXY
      059G (started at 5 minutes), the ES50 values were 3.15+/-0.50 or 2.66+/-0.82 if
      tPA administration started 60 minutes or 3 hours after embolization,
      respectively. CONCLUSIONS: This study suggests that NXY-059G is neuroprotective
      and can increase behavioral ratings if administered early after an embolic
      stroke. In addition, the study shows that NXY-059G can be used in combination
      with tPA without negative side effects. The drug combination can improve
      behavioral function and increase ES50 values. However, during the short time
      course of the behavioral analysis, the combination was not statistically better
      than either drug alone.

PMID- 11988624
TI  - Lack of evidence for pulmonary venous thrombosis in cryptogenic stroke: a
      magnetic resonance angiography study.
AB  - BACKGROUND: Even after extensive evaluation, the etiology of ischemic stroke
      remains undefined in a considerable proportion of cases, suggesting that causes
      of stroke may exist that have not yet been established. We tested the hypothesis
      that pulmonary venous thrombosis (PVT) is a potential source of brain embolism in
      patients with cryptogenic stroke. SUMMARY OF REPORT: Within 7 days after mild to
      moderately severe ischemic stroke or transient ischemic attack, 18 patients (9
      women, 9 men; mean age, 48 years) were studied in whom the etiology remained
      undefined despite complete workup. All patients received high-resolution
      pulmonary venography with the use of multiple-bolus, multiphase, 3-dimensional,
      gadolinium-enhanced MR angiography (MRA). Overall quality of the MRA was good in
      14 and insufficient in 4 patients, mainly as a result of breathing artifacts.
      Visualization of the main and segmental veins and evaluability of their patency
      were good for most right pulmonary veins but often inadequate for left pulmonary
      veins, particularly for those in the left lower lobe. There was no evidence for
      PVT in any of the sufficiently visualized pulmonary veins. CONCLUSIONS: The
      results do not support the hypothesis of PVT as a contributor to the etiology of
      ischemic stroke. However, the study was limited regarding scan volume, spatial
      discrimination, patient selection, and delay between ischemia and MRA. Therefore,
      further investigations, including postmortem studies, are needed to resolve the
      question of whether PVT may contribute to ischemic stroke.

PMID- 11988626
TI  - Acute basilar artery occlusion treated with combined intravenous Abciximab and
      intra-arterial tissue plasminogen activator: report of 3 cases.
AB  - BACKGROUND: Acute vertebrobasilar occlusion remains a disease with a high
      mortality even after treatment by local intra-arterial fibrinolysis. Adjunctive
      treatment with platelet glycoprotein IIb/IIIa receptor inhibitors such as
      abciximab may facilitate recanalization and improve the neurological outcome.
      Results after treatment of 3 patients by combined intravenous abciximab and local
      intra-arterial tissue plasminogen activator (tPA) are reported. CASE
      DESCRIPTIONS: Treatment was performed within 6 hours of stroke onset. Angiography
      revealed embolic occlusion of the basilar artery in 2 patients and
      atherothrombotic occlusion at the vertebrobasilar junction in 1 patient. Therapy
      consisted of intravenous abciximab bolus administration (0.25 mg/kg) followed by
      12-hour infusion therapy (0.125 microg/kg per minute) and local intra-arterial
      thrombolysis with tPA (10 mg/h). Heparin was only applied for catheter flushing
      (500 IU/h). The patient with the atherothrombotic occlusion was treated with
      additional percutaneous transluminal angioplasty and stenting. Complete
      recanalization of the basilar artery occurred in 2 patients, whose conditions
      improved clinically to functional independence. In the third patient only partial
      recanalization was seen, with only slight clinical improvement. This patient died
      of cardiac failure 2 months later. Besides a subtle subarachnoid hemorrhage
      (n=1), no intracranial or extracranial bleeding complication was observed.
      CONCLUSIONS: The combination of glycoprotein IIb/IIIa receptor inhibitor with
      local intra-arterial tPA might be a promising therapy for patients with acute
      vertebrobasilar occlusion. Further studies are necessary to define the clinical
      benefit and the bleeding rate of this new pharmacological approach.

PMID- 11988625
TI  - Carotid intima-media thickness is associated with allelic variants of stromelysin
      1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective
      Cohort Study.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis is a complex disorder with hereditary and
      environmental causes. Carotid artery intima-media wall thickness (IMT) is a
      useful measure of atherosclerosis. The objective of this study was to determine
      the association between carotid IMT and functional promoter variants of
      stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic
      lipase (HL: -480C>T) genes. METHODS: B-mode carotid ultrasound was performed
      among 87 subjects (mean age, 70+/-12 years; 55% women; 60% Caribbean-Hispanic,
      25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study.
      Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the
      bifurcation, the common carotid artery, and the internal carotid artery).
      RESULTS: For all polymorphisms, genotype distribution was not significantly
      different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles
      were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C,
      0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50).
      Carotid IMT in the sample was 0.78+/-0.18 mm. Subjects with the MMP3 genotype
      6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined
      (0.95+/-0.17 versus 0.87+/-0.15 mm; P=0.04). Subjects with the IL6 genotype GG
      had 11% greater IMT (0.85+/-0.17 versus 0.76+/-0.16 mm; P=0.03), and those with
      the HL genotype CC had 13% greater IMT (0.87+/-20 versus 0.76+/-0.18 mm; P=0.02)
      than the other genotypes combined. Adjustment for other risk factors did not
      change these associations. CONCLUSIONS: Carotid IMT is higher among subjects
      homozygous for functional variants in genes related to matrix deposition (MMP3 
      16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These
      associations were independent of race-ethnicity and some environmental exposures.
      Further studies are needed to confirm these genotype-phenotype associations.

PMID- 11988627
TI  - Cerebral infarction due to carotid occlusion caused by cervical vagal
      neurilemmoma: report of a case.
AB  - BACKGROUND: We report a case of a 71-year-old woman with cerebral infarction due
      to occlusion of the internal carotid artery (ICA) caused by a neck tumor. CASE
      DESCRIPTIONS: In 1998, the patient complained of mild hoarseness, and a
      diagnostic workup showed a cervical mass that was considered a benign neck tumor.
      In September 2000, she developed right-sided weakness. Diffusion-weighted MRI
      showed a high-intensity area in the territory of the left middle cerebral artery.
      Carotid angiography and ultrasonography revealed occlusion of the left ICA, which
      was due to compression by the neck tumor. Superficial temporal artery-middle
      cerebral artery anastomosis was performed to prevent critical reduction of
      cerebral blood flow in the left ICA territory; this was followed by tumor
      resection. The occluded ICA recanalized after tumor resection. Microscopic
      examination showed that the tumor was a vagal neurilemmoma. CONCLUSIONS: This is
      the first case of cerebral infarction due to left ICA occlusion by a cervical
      neurilemmoma. Even when the neck tumor is benign, it may occlude the ICA and
      thereby cause cerebral infarction.

PMID- 11988628
TI  - Falls, fractures, and osteoporosis after stroke: time to think about protection?
AB  - BACKGROUND: Osteoporosis is a significant complication of stroke. The clinical
      course of hemiplegic stroke predisposes patients to disturbed bone physiology.
      Sudden immobility and unilateral loss of function unload the skeleton at key
      areas such as the affected hip. This is manifest by an early reduction in bone
      density at this site. Stroke patients may also have motor, sensory, and
      visual/perceptual deficits that predispose them to falls. These factors result in
      an early but sustained increase in hip fractures after stroke. SUMMARY OF
      COMMENT: Potential bone loss is often overlooked in stroke treatment. Morbidity
      and mortality from hip fractures might be reduced by preventing bone loss at an
      early stage. In the crucial first year after stroke, bone loss seems to be due to
      accelerated resorption. Bisphosphonates are the drugs of choice in preventing
      osteoclastic bone resorption, but oral administration soon after stroke may be
      impractical. Potent new intravenous bisphosphonates have been used in
      postmenopausal women with osteoporosis with good preliminary results. Effective
      dosing regimens for osteoporosis have included a single annual or semiannual
      injection of bisphosphonate as well as weekly oral dosing. This article reviews
      the current literature on osteoporosis and hip fractures after stroke, making a
      case for a trial of intravenous bisphosphonates early after stroke. CONCLUSIONS:
      Hip fracture after stroke is an increasingly recognized problem. Measures to
      prevent bone loss and preserve bone architecture have not been part of stroke
      management thus far. Because rapid bone loss is a risk factor for fracture, we
      believe that a randomized, placebo-controlled trial of intravenous
      bisphosphonates given in the early phase of stroke rehabilitation is indicated.

PMID- 11988629
TI  - Thrombolytic therapy within 3 to 6 hours after onset of ischemic stroke: useful
      or harmful?
AB  - BACKGROUND: The use of recombinant tissue plasminogen activator (rtPA) within 3
      hours after onset of an ischemic stroke is an established therapy. Because the
      use of intravenous rtPA beyond a time window of 3 hours after stroke onset is
      still a matter of debate, we sought to review the evidence for the use of
      thrombolytic therapy in a time window up to 6 hours after onset of symptoms of
      ischemic stroke. SUMMARY OF REVIEW: The meta-analyses of the major trials
      (National Institute of Neurological Disorders and Stroke rtPA Stroke Study,
      European Cooperative Acute Stroke Study [ECASS] I, ECASS II) showed a benefit of
      thrombolytic therapy with intravenous rtPA even within 6 hours after onset of
      symptoms of ischemic stroke. The rate of intracerebral hemorrhage was slightly
      increased in the 6-hour time window compared with the 3-hour time window (odds
      ratio, 3.23 versus 2.68), but this was without statistical significance because
      of wide confidence intervals. A positive effect of 37% relative odds reduction
      with the use of a dichotomization of < or =2 versus > or =3 on the modified
      Rankin Scale remains for rtPA treatment within 6 hours. However, the Alteplase
      Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS)
      Study, in which a 3- to 5-hour time window was used, failed to show a benefit of
      rtPA. Still, when the results of ATLANTIS are included into meta-analyses such as
      the Cochrane Library, the positive effect of rtPA treatment in the 6-hour time
      window remains, with a "number needed to treat" value of 11. Treating patients
      only within a 3- to 6-hour time window would lead to a number needed to treat
      value of 25. CONCLUSIONS: Consequently, from our point of view it appears
      unjustified to limit thrombolytic therapy to 3 hours. Because of lack of
      approvals for 3 to 6 hours, thrombolytic therapy within this time window should
      be done only as part of an institutional protocol after extensive information is
      obtained from the patient and the patient's relatives. Better methods for patient
      selection are required; in particular, newer MRI techniques, such as diffusion-
      and perfusion-weighted imaging, can play a key role. The aim is to qualify and
      individualize the time window according to the findings in each patient's imaging
      results rather than to use a strictly time-defined therapeutic window.

PMID- 11988630
TI  - Axial distortion as a sensor of supercoil changes: a molecular model for the
      homeostatic regulation of DNA gyrase.
AB  - Negative supercoiling stimulates transcription of many genes. In contrast,
      transcription of the genes coding for DNA gyrase is subject to a novel mechanism
      of autoregulation, wherein relaxation of the template DNA stimulates their
      transcription. Since DNA gyrase is the sole supercoiling activity in the
      eubacterial cell, relaxation-stimulated transcription (RST) could reflect an
      autoregulatory mechanism to maintain supercoil levels within the cell. Extensive
      deletion and mutational analyses of Escherichia coli gyrA promoter have shown
      that the -10 region is essential for RST; however, a molecular model has proved
      to be elusive. We find a strong bend centre immediately downstream of the -10
      region in the gyrA promoter. On the basis of analysis of various mutants in the 
      10 region, we propose a model where axial distortion acts as a sensor of
      topological changes in DNA. Our model is consistent with earlier data with E.
      coli gyrA anmd gyrB promoters. We also extrapolate the model to explain the
      phenomenon of RST of gyr promoters in other organisms and contrast it with
      promoters induced by supercoiling.

PMID- 11988631
TI  - High-resolution analysis of Y-chromosomal polymorphisms reveals signatures of
      population movements from Central Asia and West Asia into India.
AB  - Linguistic evidence suggests that West Asia and Central Asia have been the two
      major geographical sources of genes in the contemporary Indian gene pool. To test
      the nature and extent of similarities in the gene pools of these regions we have
      collected DNA samples from four ethnic populations of northern India, and have
      screened these samples for a set of 18 Y-chromosome polymorphic markers (12
      unique event polymorphisms and six short tandem repeats). These data from Indian
      populations have been analysed in conjunction with published data from several
      West Asian and Central Asian populations. Our analyses have revealed traces of
      population movement from Central Asia and West Asia into India. Two haplogrops,
      HG-3 and HG-9, which are known to have arisen in the Central Asian region, are
      found in reasonably high frequencies (41.7% and 14.3% respectively) in the study
      populations. The ages estimated for these two haplogroups are less in the Indian
      populations than those estimated from data on Middle Eastern populations. A
      neighbour-joining tree based on Y-haplogroup frequencies shows that the North
      Indians are genetically placed between the West Asian and Central Asian
      populations. This is consistent with gene flow from West Asia and Central Asia
      into India.

PMID- 11988632
TI  - Distribution of HIV-1 resistance-conferring polymorphic alleles SDF-1-3'A, CCR2
      64I and CCR5-Delta32 in diverse populations of Andhra Pradesh, South India.
AB  - Polymorphic allelic variants of chemokine receptors CCR2 and CCR5, as well as of
      stromal-derived factor-1 SDF-1, the ligand for the chemokine receptor CXCR4, are
      known to have protective effects against HIV-1 infection and to be involved with
      delay in disease progression. We have studied the DNA polymorphisms at the loci
      that encode these proteins in 525 healthy individuals without any history of HIV
      1 infection from 11 diverse populations of Andhra Pradesh, South India. The two
      protective alleles SDF-1-3'A and CCR2-64I at the SDF-1 and CCR2 loci,
      respectively, are present in all populations studied, although their frequencies
      differ considerably across populations (from 17% to 35% for the SDF-1-3'A allele,
      and from 3% to 17% for CCR2-64I). In contrast the CCR5-Delta32 allele is observed
      only in three populations (Yamani, Pathan and Kamma), all in low frequencies
      (i.e. 1% to 3%). The mean number of mutant alleles (for the three loci together)
      carried by each individual varies from 0.475 (in Vizag Brahmins) to 0.959 (in
      Bohra Muslims). The estimated relative hazard values for the populations,
      computed from the three-locus genotype data, are comparable to those from Africa
      and Southeast Asia, where AIDS is known to be widespread.

PMID- 11988633
TI  - Genetic variation and population structure in Oryza malampuzhaensis Krish. et
      Chand. endemic to Western Ghats, South India.
AB  - Oryza malampuzhaensis Krish. et Chand. (2n = 4x = 48; Poaceae, Oryza) is endemic
      to Western Ghats, South India, and shows a highly localized distribution over a
      small geographical area in this region. This is the most poorly understood taxon
      in genus Oryza and is often misidentified as O. officinalis owing to their close
      morphology. We assessed the nature and distribution of genetic variation among 11
      populations of O. malampuzhaensis using random amplified polymorphic DNA markers.
      The analysis revealed low genetic variation in O. malampuzhaensis. Cluster
      analysis of pairwise genetic distances of populations revealed three distinct
      clusters and the grouping of populations largely corresponded to their
      geographical proximity. Restricted gene flow and a geography-dependent
      differentiation were evident among populations. The altitude-influenced
      differences in ecological factors among the natural habitats of the populations
      seem to be the cause of the geography-dependent differentiation. Genetically
      isolated smaller populations and a narrow genetic base in O. malampuzhaensis
      point to its vulnerability to genetic drift and genetic depauperation. Thus O.
      malampuzhaensis appears to be under the threat of extinction and needs to be
      conserved by use of suitable methods. The present study also identified molecular
      markers diagnostic for O. malampuzhaensis.

PMID- 11988634
TI  - Evaluation of the genetic variability of 13 microsatellite markers in native
      Indian pigs.
AB  - We analysed polymorphism of 13 microsatellites in two Indian domesticated pig
      types (North Indian and Northeast Indian). Heterozygosity, polymorphism
      information content, and probability of identity of two random individuals were
      calculated for all microsatellites in both types. The number of alleles observed
      at a locus varied between five and 12. The evaluated microsatellites exhibited a
      very high heterozygosity and polymorphism information content. The probability of
      identity of two random individuals from different populations taking into account
      all the 13 microsatellites was as low as 3.51 x 10(-19). On the basis of these
      results, we propose that these microsatellite markers may be used with
      reliability for studying the genetic diversity and for identification of
      individuals in Indian pig types.

PMID- 11988635
TI  - Introduction to special issue on myocardial energy metabolism in heart failure.

PMID- 11988636
TI  - Energy metabolism in the normal and failing heart: potential for therapeutic
      interventions.
AB  - The chronically failing heart has been shown to be metabolically abnormal, in
      both animal models and in patients. Little data are available on the rate of
      myocardial glucose, lactate and fatty acid metabolism and oxidation in heart
      failure patients, thus at present, it is not possible to draw definitive
      conclusions about cardiac substrate preference in the various stages and
      manifestations of the disease. Normal cardiac function is dependent on a constant
      resynthesis of ATP by oxidative phosphorylation in the mitochondria. The healthy
      heart gets 60-90% of its energy for oxidative phosphorylation from fatty acid
      oxidation, with the balance from lactate and glucose. There is some indication
      that compensated NYHA Class III heart failure patients have a significantly
      greater rate of lipid oxidation, and decreased glucose uptake and carbohydrate
      oxidation compared to healthy age-matched individuals, and that therapies that
      acutely switch the substrate of the heart away from fatty acids result in
      improvement in left ventricular function. Clinical studies using long-term
      therapy with beta-adrenergic receptor antagonists show improved left ventricular
      function that corresponds with a switch away from fatty acid oxidation towards
      more carbohydrate oxidation by the heart. These findings suggest that chronic
      manipulation of myocardial substrate oxidation toward greater carbohydrate
      oxidation and less fatty acid oxidation may improve ventricular performance and
      slow the progression of left ventricular dysfunction in heart failure patients.
      At present, this intriguing hypothesis requires further evaluation.

PMID- 11988637
TI  - Electron transport chain defects in heart failure.
AB  - In recent years, the possibility that disorders of cardiac metabolism play a role
      in the mechanisms that lead to ventricular dilatation and dysfunction in heart
      failure has attracted much attention. Electron transport chain is constituted by
      a series of multimeric protein complexes, located in the inner mitochondrial
      membranes, whose genes are distributed over both nuclear and mitochondrial DNA.
      Its normal function is essential to provide the energy for cardiac function. Many
      studies have described abnormalities in mitochondrial DNA genes encoding for
      electron transport chain (ETC) in dilated cardiomyopathies. In some cases, heart
      failure is one more or less relevant symptom among other multisystem
      manifestations characteristic of mitochondrial encephalomyopathies, being heart
      failure imputable to a primary mitochondrial disease. In the case of idiopathic
      dilated cardiomyopathies (IDC), many mitochondrial abnormalities have also been
      described using hystological, biochemical or molecular studies. The importance of
      such findings is under debate. The great variability in the mitochondrial
      abnormalities described has prompted the proposal that mitochondrial dysfunction
      could be a secondary phenomenon in IDC, and not a primary one. Among other
      possible explanations for such findings, the presence of an increased oxidative
      damage due to a free radical excess has been postulated. In this setting, the
      dysfunction of ETC could be a consequence, but also a cause of the presence of an
      increased free radical damage. Independently of its origin, ETC dysfunction may
      contribute to the persistence and worsening of heart failure. If this hypothesis,
      still to be proven, was certain, the modulation of cardiac metabolism could be an
      interesting approach to treat IDC. The precise mechanisms that lead to
      ventricular dilatation and dysfunction in heart failure are still nowadays poorly
      understood. Circumstances such as cytotoxic insults, viral infections, immune
      abnormalities, contractile protein defects, ischemic factors and familial
      conditions have been thoroughly investigated [1]. It is possible that several
      mechanisms combine to produce the clinical syndrome of heart failure. In recent
      years the possibility that disorders of energy metabolism, either isolated or in
      combination with the other aforementioned factors, may play a role in the
      development of heart failure in susceptible patients has attracted much
      attention. The present paper reviews the current knowledge on mitochondrial
      function in the failing myocardium. We restrain our discussion to heart failure
      where an impaired inotropic state leads to a weakened systolic contraction (i.e.
      the so-called systolic heart failure). Idiopathic dilated cardiomyopathy (IDC) is
      the prototype of the conditions under discussion. Other circumstances where a
      defect in myocardial contraction is due to a chronic excessive work load (i.e.,
      hypertension, valvular or congenital heart diseases), and states in which the
      principal abnormality involves impaired relaxation of the ventricle (i.e.
      diastolic heart failure), as well as mitochondrial defects outside the electron
      transport chain (i.e., defects in Krebs cycle or beta-oxidation of fatty acids)
      are only approached circumstantially.

PMID- 11988638
TI  - Role of nitric oxide in the regulation of substrate metabolism in heart failure.
AB  - Solid experimental evidence indicates that nitric oxide (NO) inhibits oxygen
      utilization in vitro and in vivo. The role played by NO in cellular metabolism is
      likely extended to the control of substrate utilization. Studies performed in
      normal hearts show that NO inhibits glucose uptake and that a reduced synthesis
      of NO impairs free fatty acid consumption. Interestingly, we found also that
      myocardial free fatty acid utilization decreases while glucose consumption is
      enhanced in end stage heart failure, when cardiac NO production falls
      dramatically. This phenomenon led us to the hypothesis that the reduced synthesis
      of NO could be at least in part responsible for myocardial metabolic alterations
      occurring in severe heart failure. The present review mentions some of the
      seminal studies that defined the function of NO as metabolic modulator. A
      particular emphasis is put on available data suggesting a role for NO in the
      control of cardiac substrate utilization in normal and failing hearts.

PMID- 11988639
TI  - Metabolic abnormalities in the diabetic heart.
AB  - Congestive heart failure is a major health problem in the diabetic. Diabetics
      have a high incidence of heart disease, including an increased incidence and
      severity of congestive heart failure than the non-diabetic. Progression to heart
      failure after an acute myocardial infarction is also more frequent in diabetics
      then non-diabetics. While atherosclerosis and ischemic injury are important
      contributing factors to this high in incidence of heart failure, another
      important factor is diabetes-induced changes within the heart itself. A prominent
      change that occurs in the diabetic is a switch in cardiac energy metabolism.
      Increases in fatty acid oxidation accompanied by decreases in glucose metabolism
      can result in the myocardium becoming almost entirely reliant on fatty acid
      oxidation as a source of energy. This switch in energy metabolism contributes to
      congestive heart failure by increasing the severity of injury following an acute
      myocardial infarction, and by having direct negative effects on contractile
      function. This paper will review the evidence linking alterations in energy
      metabolism to alterations in contractile function in the diabetic.

PMID- 11988640
TI  - Energy metabolism in the hypertrophied heart.
AB  - In response to a prolonged pressure- or volume-overload, alterations occur in
      myocardial fatty acid, glucose, and glycogen metabolism. Oxidation of long chain
      fatty acids has been found to be reduced in hypertrophied hearts compared to non
      hypertrophied hearts. However, this observation depends upon the degree of
      cardiac hypertrophy, the severity of carnitine deficiency, the concentration of
      fatty acid in blood or perfusate, and the myocardial workload. Glycolysis of
      exogenous glucose is accelerated in hypertrophied hearts. Despite the
      acceleration of glycolysis, glucose oxidation is not correspondingly increased
      leading to lower coupling between glycolysis and glucose oxidation and greater
      H(+) production than in non-hypertrophied hearts. Although glycogen metabolism
      does not differ in the absence of ischemia, synthesis and degradation of glycogen
      are accelerated in severely ischemic hypertrophied hearts. These alterations in
      carbohydrate metabolism may contribute to the increased susceptibility of
      hypertrophied hearts to injury during ischemia and reperfusion by causing
      disturbances in ion homeostasis that reduce contractile function and efficiency
      to a greater extent than normal. As in non-hypertrophied hearts, pharmacologic
      enhancement of coupling between glycolysis and glucose oxidation (e.g., by
      directly stimulating glucose oxidation) improves recovery of function of
      hypertrophied hearts after ischemia. This observation provides strong support for
      the concept that modulation of energy metabolism in the hypertrophied heart is a
      useful approach to improve function of the hypertrophied heart during ischemia
      and reperfusion. Future investigations are necessary to determine if alternative
      approaches, such as glucose-insulin-potassium infusion and inhibitors of fatty
      acid oxidation (e.g., ranolazine, trimetazidine), also produce beneficial effects
      in ischemic and reperfused hypertrophied hearts.

PMID- 11988641
TI  - Gene regulatory mechanisms governing energy metabolism during cardiac
      hypertrophic growth.
AB  - Studies in a variety of mammalian species, including humans, have demonstrated a
      reduction in fatty acid oxidation (FAO) and increased glucose utilization in
      pathologic cardiac hypertrophy, consistent with reinduction of the fetal energy
      metabolic program. This review describes results of recent molecular studies
      aimed at delineating the gene regulatory events which facilitate myocardial
      energy substrate switches during hypertrophic growth of the heart. Studies aimed
      at the characterization of transcriptional control mechanisms governing FAO
      enzyme gene expression in the cardiac myocyte have defined a central role for the
      fatty acid-activated nuclear receptor peroxisome proliferator-activated receptor
      alpha (PPAR(alpha)). Cardiac FAO enzyme gene expression was shown to be
      coordinately downregulated in murine models of ventricular pressure overload,
      consistent with the energy substrate switch away from fatty acid utilization in
      the hypertrophied heart. Nuclear protein levels of PPAR(alpha) decline in the
      ventricle in response to pressure overload, while several Sp and nuclear receptor
      transcription factors are induced to fetal levels, consistent with their binding
      to DNA as transcriptional repressors of rate-limiting FAO enzyme genes with
      hypertrophy. Knowledge of key components of this transcriptional regulatory
      pathway will allow for the development of genetic engineering strategies in mice
      that will modulate fatty acid oxidative flux and assist in defining whether
      energy metabolic derangements play a primary role in the development of
      pathologic cardiac hypertrophy and eventual progression to heart failure.

PMID- 11988642
TI  - Metabolic approaches to the treatment of ischemic heart disease: the clinicians'
      perspective.
AB  - This review article discusses pharmacological approaches to optimizing myocardial
      metabolism during ischemia. Fatty acids are the main fuel for the healthy heart,
      with a lesser contribution coming from the oxidation of glucose and lactate.
      Myocardial ischaemia dramatically alters fuel metabolism, causing an accelerated
      rate of glucose conversion to lactate and a switch from lactate uptake by the
      heart to lactate production. This causes a dramatic disruption in cell
      homeostasis (e.g. lactate accumulation and a decrease in pH and ATP).
      Paradoxically, moderately ischemic tissue (approximately 50% of normal flow)
      continues to derive most of its energy (50-70%) from the oxidation of fatty acids
      despite a high rate of lactate production. This ischaemia-induced disruption in
      cardiac metabolism can be minimized by metabolic agents that reduce fatty acid
      oxidation and increase the combustion of glucose and lactate, resulting in
      clinical benefit to the ischemic patient. Agents that inhibit fatty acid beta
      oxidation, such as ranolazine and trimetazidine, have proven to be effective in
      the treatment of stable angina. Treatment of acute myocardial infarction patients
      with an infusion of the glucose-insulin-potassium, which results in suppression
      of myocardial fatty acid oxidation and greater glucose combustion, has proven
      effective in reducing mortality. These metabolic therapies are free of direct
      hemodynamic or chronotropic effects, and thus are well positioned for use
      alongside traditional agents such as beta-adrenergic receptor antagonists or
      calcium channel antagonists.

PMID- 11988644
TI  - The G-->A single nucleotide polymorphism at the -308 position in the tumor
      necrosis factor-alpha promoter increases the risk for severe sepsis after trauma.
AB  - BACKGROUND: Clinical factors do not adequately explain why some patients develop
      severe sepsis after trauma and why others do not. We sought to determine whether
      genetic factors contribute to this risk. METHODS: Patients admitted to a single
      Level I trauma center were enrolled and DNA was isolated from leukocytes. The
      risk for severe sepsis and for death associated with polymorphism in the tumor
      necrosis factor-alpha promoter was determined by multivariate analysis. RESULTS:
      One hundred fifty-two patients had a 24% incidence of severe sepsis and a 13%
      case fatality rate. The A-allele was most common at the -308 position (n = 35). A
      allele carriage at this location was associated with an adjusted odds ratio of
      4.6 (95% confidence interval, 1.9-10.9) for severe sepsis and of 2.1 (95%
      confidence interval, 0.6-7.3) for death. CONCLUSION: The A-allele at the -308
      position in the tumor necrosis factor-alpha promoter increases the risk for
      severe sepsis and possibly for death after trauma.

PMID- 11988645
TI  - Relative importance of designation and accreditation of trauma centers during
      evolution of a regional trauma system.
AB  - BACKGROUND: Improved survival after injury has been demonstrated with trauma
      system implementation and designation of trauma centers. Local designating health
      authorities or national verification (United States) or accreditation (Canada)
      programs audit trauma center performance. The relative importance of designation
      versus accreditation with respect to improved outcomes is not clear. The purpose
      of this study was to measure outcomes within a single regional trauma system
      after designation of trauma centers and to compare outcomes in the one accredited
      center to the nonaccredited centers. METHODS: Data from three trauma centers were
      studied. All were large, university-affiliated regional medical centers,
      integrated into a regional trauma system and served by a single ambulance
      service. The study period was 1992 to 1999, immediately after trauma center
      designation in 1991. The British Columbia Trauma Registry was used to identify
      trauma patients, mechanism of injury, length of stay, case mix, case volume,
      acuity, pediatric caseload, and proportion of transfers at each center. A
      questionnaire was circulated to each hospital to determine the level of
      institutional support and programmatic development for trauma. The Trauma
      Registry was used to calculate z scores (TRISS methodology) for each center and
      TRISS-adjusted mortality odds ratios between institutions. Differences in
      covariables were controlled for in subgroup analysis. RESULTS: Two centers
      (hospitals A and C) had a high trauma caseload; one (hospital B) had a small and
      diminishing caseload. Only one center (hospital A) developed a trauma program
      consistent with Canadian accreditation criteria; z scores for center A were
      consistently better than at hospital B or C and survival odds ratios were
      significant. This finding applied to the total trauma population, blunt adult
      trauma patients (whether or not transfers and hip fracture patients were
      excluded), and in the more severely injured blunt trauma subgroups. There were no
      differences between hospitals for the relatively small number of patients with
      penetrating trauma. CONCLUSION: Differences between hospitals were apparent from
      the outset of the trauma system. However, designation as a trauma center does not
      appear to necessarily improve survival in large regional medical centers.
      Development of a trauma program and commitment to meeting national guidelines
      through the accreditation process does appear to be associated with improved
      outcome after injury.

PMID- 11988643
TI  - Aldosterone receptor blockade in the management of heart failure.
AB  - Mounting evidence suggests that increased circulating aldosterone levels, despite
      angiotensin-converting-enzyme inhibitors therapy, may exert deleterious
      cardiovascular effects in heart failure, leading to clinical deterioration and
      poor prognosis. In the past decades, a number of experimental investigations have
      provided major insight into the mechanism(s) of action and the biological effects
      of aldosterone on the cardiovascular system, indicating that aldosterone
      participates in the structural and functional remodeling of cardiac and vascular
      tissue. In particular, it has emerged that aldosterone plays a key role in the
      regulation of myocardial extracellular matrix composition and endothelial
      function with important pathophysiological implications. Such evidence, coupled
      with the recent beneficial effects of spironolactone, a competitive aldosterone
      receptor antagonist, in reducing cardiac mortality and morbidity in patients with
      severe chronic heart failure treated with angiotensin-converting-enzyme
      inhibitors and loop diuretics, highlights the importance of aldosterone in the
      pathophysiology of human heart failure. The purpose of this review is to provide
      an overview of the regulation of aldosterone production and metabolism in heart
      failure, the basic mechanism of aldosterone action, and the pathophysiological
      implications of aldosterone in heart failure, and to discuss recent evidence
      supporting the efficacy of aldosterone receptor blockade in the treatment of
      chronic heart failure in humans.

PMID- 11988646
TI  - The profile of level I trauma center directors.
AB  - BACKGROUND: No data are available regarding the characteristics of the trauma
      directors of Level I trauma centers. METHODS: Questionnaires were mailed to 102
      directors of Level I trauma centers. Data were analyzed in a blinded fashion.
      RESULTS: Seventy-two directors responded. All were men, with a mean age of 48 +/-
      6 years. Fifty-eight percent of directors were fellowship trained. Directorship
      was assumed 7.3 +/- 6.1 years after training and the average time on the job was
      8.6 +/- 6.1 years. Directors work in urban (93%), university-affiliated (67%)
      institutions that admit 1,000 to 2,000 patients annually (50%). Practice time
      distribution is as follows: trauma clinical care, 33%; general surgery, 20%;
      administrative work, 18%; critical care delivery, 17%; and research, 11%.
      Directors take 6.6 +/- 2.2 night calls per month, with half of them taking in
      house call. Eighty-eight percent of directors are involved in research. Seventy
      eight percent of directors earn $200,000 to $325,000 per year, with the largest
      group making $225,000 to $250,000. Salary is derived from clinical revenues (42%)
      and hospital (37%) or university (20%) support. Compensation is higher in
      community hospitals and tends to be higher in the Midwest. CONCLUSION: The
      profile of the trauma director at a Level I trauma center was described. This may
      be important in trauma career and systems development.

PMID- 11988647
TI  - The Outreach Trauma Program: a model for survival of the academic trauma center.
AB  - BACKGROUND: In the current health care climate, trauma centers face particular
      economic challenges. Statewide trauma systems provide a network for referral of
      critically injured patients to academic Level I trauma centers, but favorable
      reimbursement in states such as Colorado results in intense competition for
      patients. We hypothesized that a comprehensive Outreach Trauma Program would
      facilitate our mission as a key resource facility in our trauma system, and would
      increase referrals of critically injured patients to our center from outside our
      metropolitan area. METHODS: The Colorado statewide trauma system was formalized
      in 1995; our Outreach program-including providing visiting trauma call,
      continuing medical education lectures, 24-hour/7-day immediate consultation and
      transfers, and public relations/marketing-was fully implemented in 1997. We
      audited our trauma registry from January 1994 to July 2001 to determine the
      impact on patient volume and acuity as well as academic productivity. RESULTS:
      Annual overall trauma admissions have remained stable. Since 1997, high-acuity
      patients (i.e., Injury Severity Score > 15, intensive care unit admissions, those
      requiring surgery) have increased 27% to 51%, attributable largely to an
      approximately 300% increase in high-acuity Outreach patients. In 2000, Outreach
      patients constituted 8% of our total trauma admissions, but 21% of intensive care
      unit trauma admissions; notably, they accounted for 25% of our center's trauma
      charges. Meanwhile, our group's academic productivity has not suffered; in fact,
      we had 57 publications in 2000, compared with an average of 35 per year from 1993
      through 1997. CONCLUSION: The Outreach Trauma Program has proven clinically,
      academically, and financially rewarding. Our program may serve as a model whereby
      academic trauma centers, through a demonstrated commitment to serving the
      clinical and educational needs of their referral base, can satisfy their mission
      while ensuring their survival.

PMID- 11988648
TI  - Teaching effectiveness of the trauma evaluation and management module for senior
      medical students.
AB  - BACKGROUND: The Trauma Evaluation and Management (TEAM) module was devised by the
      American College of Surgeons for teaching senior medical students trauma
      management principles. This article reports on the teaching effectiveness of this
      module. METHOD: Cognitive skills (by 20 item multiple-choice question examination
      on trauma topics) and clinical trauma management skills performance, using the
      Objective Structured Clinical Examination, were compared between two groups of 16
      randomly selected final year medical students who had completed the standard
      curriculum including trauma topics. One group had the TEAM (TEAM group) and the
      other did not (no-TEAM group). Objective Structured Clinical Examination score
      (percentage), Priority score (range, 1-7), Organized Approach score (range, 1-5),
      and Global Pass status were assigned at each station. The students also completed
      a five-part questionnaire. RESULTS: Results of the questionnaire showed that on a
      scale of 1 to 5, with 5 being excellent, 96.8% assigned a score of 4 or greater,
      indicating the objectives were met, 83.8% that trauma knowledge was improved,
      51.6% that clinical skills were improved, 90.3% that the module should be
      mandatory, and 83.9% overall satisfaction with the program. CONCLUSION: The TEAM
      module is very effective in teaching trauma management principles to senior
      medical students, by whom the program was very well received. Consideration
      should be given to adopting this program more widely in our medical undergraduate
      curriculum.

PMID- 11988649
TI  - Bullet trajectory predicts the need for damage control: an artificial neural
      network model.
AB  - BACKGROUND: Effective use of damage control in trauma hinges on an early decision
      to use it. Bullet trajectory has never been studied as a marker for damage
      control. We hypothesize that this decision can be predicted by an artificial
      neural network (ANN) model based on the bullet trajectory and the patient's blood
      pressure. METHODS: A multilayer perceptron ANN predictive model was developed
      from a data set of 312 patients with single abdominal gunshot injuries. Input
      variables were the bullet path, trajectory patterns, and admission systolic
      pressure. The output variable was either a damage control laparotomy or
      intraoperative death. The best performing ANN was implemented on prospectively
      collected data from 34 patients. RESULTS: The model achieved a correct
      classification rate of 0.96 and area under the receiver operating characteristic
      curve of 0.94. External validation showed the model to have a sensitivity of 88%
      and specificity of 96%. Model implementation on the prospectively collected data
      had a correct classification rate of 0.91. Sensitivity analysis showed that
      systolic pressure, bullet path across the midline, and trajectory involving the
      right upper quadrant were the three most important input variables. CONCLUSION:
      Bullet trajectory is an important, hitherto unrecognized, factor that should be
      incorporated into the decision to use damage control.

PMID- 11988650
TI  - Incidence and characteristics of motor vehicle collision-related blunt thoracic
      aortic injury according to age.
AB  - BACKGROUND: Motor vehicle collision-related blunt thoracic aorta injury (BAI) is
      rare and highly lethal. Vascular disease as related to advancing age potentially
      subjects older adults to increased risk of BAI; the mechanisms associated with
      such injuries may be different as compared with younger adults. The goal of the
      present study is to test this hypothesis using population-based data. METHODS:
      The 1995 to 1999 National Automotive Sampling System data files were used. The
      National Automotive Sampling System is a national probability sample of passenger
      vehicles involved in police-reported tow-away crashes. BAI was defined according
      to the Abbreviated Injury Scale codes. Among those with BAI, information on
      occupant (age, seating position, restraint use), collision (collision type, delta
      V, vehicle intrusion), and outcome characteristics were obtained and compared
      according to age. RESULTS: The overall incidence of BAI was 6.8 per 10,000
      occupants and there was a steady increase in the BAI rate for advancing decades
      of life. The proportion of occupants with BAI who die at the scene of the
      collision is relatively consistent across all age groups ( approximately 85%).
      Among those who survive to receive medical care, ultimate survival is lowest
      among those aged 60 and older. Near-side collisions were responsible for more BAI
      among older adults than other age groups (50% vs. 20.6%, p < or = 0.05). Older
      adults sustained BAI in collisions with lower delta-V values compared with
      younger persons (p < or = 0.05). CONCLUSION: Older adults have the highest rate
      of motor vehicle collision-related BAI, and their injuries tend to occur in less
      severe collisions. A high level of suspicion for BAI among older adults should
      not be reserved for high-energy collisions only.

PMID- 11988651
TI  - Cytokine expression profiling in human leukocytes after exposure to hypertonic
      and isotonic fluids.
AB  - BACKGROUND: Resuscitation from hemorrhagic shock causes profound immunologic
      changes. The tonicity of fluids used for resuscitation clearly influences the
      immune response. Our study was designed to determine whether isotonic and
      hypertonic fluids exert their differential effects on immune response by altering
      the cytokine gene profile of human leukocytes. The cDNA array method was used to
      profile transcriptional responses after exposure to hypertonic and isotonic
      fluids. METHODS: Blood from seven healthy volunteers was incubated for 30 minutes
      with isotonic (10% dextran-40 and lactated Ringer's [LR] solution) and hypertonic
      (7.5% hypertonic saline and hypertonic dextran [HTD]) fluids. The volumes of
      isotonic fluids used were equal to the volume of blood, whereas the volumes of
      hypertonic fluids were adjusted to keep the salt load identical to the LR group.
      The cDNA array technique was used to measure the gene expression of 23 common
      cytokines. RESULTS: Increased gene transcription of proinflammatory cytokines
      (interleukin [IL]-1alpha, IL-6, IL-10, and tumor necrosis factor-alpha) as well
      as others (IL-5, IL-7, and IL-16) was found after incubation with resuscitation
      fluids. Variances were noted depending on the type of fluid: HTD and LR solution
      did not induce expression of IL-5, and HTD also did not induce IL-1beta
      expression. Genes encoding IL-1alpha, IL-6, IL-9, and tumor necrosis factor-alpha
      had low level baseline expression in leukocytes isolated from unstimulated blood,
      and their expression increased markedly after exposure to resuscitation fluids.
      The inducible transcripts included IL-1beta, IL-7, IL-10, and IL-16. However,
      there was no difference in cytokine expression profile between isotonic and
      hypertonic fluids. CONCLUSION: Exposure of human leukocytes to resuscitation
      fluids causes an increase in cytokine gene expressions compared with undiluted
      blood. This expression profile is largely independent of the type of fluid used.

PMID- 11988652
TI  - Effects of lactated Ringer's solutions on human leukocytes.
AB  - BACKGROUND: The standard lactated Ringer's (LR) solution contains racemic
      lactate, an equal mixture of D(-)- and L(+)-isomers. The aim of this study was to
      investigate whether racemic LR solution (containing both isomers, dl-LR) differs
      from LR containing L-isomer only (L-LR). METHODS: Blood from 20 volunteers was
      incubated for 30 minutes with lactated Ringer's solutions containing the DL- or L
      form of lactate, Hank's balanced salt solution, normal saline, and ketone
      Ringer's (lactate replaced with ketone bodies). Neutrophil "oxidative burst" was
      measured using flow cytometry. Gene expression of 23 genes associated with
      leukocyte function was determined with cDNA array technique. The arraying
      procedure was repeated four times to obtain four sets of data. RESULTS: Compared
      with the L-LR and ketone Ringer's, DL-LR causes an increased production of
      reactive oxygen species by neutrophils and affects expression of leukocyte genes
      known to be involved in inflammation, cell migration, and apoptosis. CONCLUSION:
      Lactated Ringer's solution in commonly used formulation (racemic mixture, DL-LR)
      influences neutrophil function and leukocyte gene expression.

PMID- 11988653
TI  - Prehospital intubation in severe thoracic trauma without respiratory
      insufficiency: a matched-pair analysis based on the Trauma Registry of the German
      Trauma Society.
AB  - OBJECTIVE: On the basis of the data of a multicenter study, the impact of
      prehospital intubation and ventilation in the therapy of severe thoracic trauma
      without manifest respiratory insufficiency was analyzed. METHODS: Data were
      collected prospectively in the Trauma Registry of the German Trauma Society. In a
      matched-pair analysis, patients with severe thoracic trauma (Abbreviated Injury
      Scale score of 4) with and without prehospital intubation were compared. Patients
      were paired with respect to age, injury severity, and prognosis (according to the
      TRISS method). RESULTS: From a total of 3,814 patients, two groups (with/without
      prehospital intubation) of 44 matched patients each with comparable average age
      (36 vs. 36 years), Injury Severity Score (29 vs. 29), and TRISS (95.2 vs. 95.3)
      were identified. No patient was unconscious at the scene (all Glasgow Coma Scale
      scores > or = 8) or presented with severe respiratory insufficiency (all > or =
      10 breaths/min). Time between injury and hospital admission was significantly
      longer (73 minutes; p < 0.05) in the group with prehospital intubation compared
      with the nonintubated group (47 minutes). Furthermore, fluid requirements in the
      prehospital period were significantly higher in the intubated patients (3,000 mL
      vs. 1,000 mL). In the prehospital intubation group, the number of patients with
      mass transfusion (9 vs. 4) as well as with emergency operations (10 vs. 4) were
      not significantly different from the nonintubated group. The prehospital
      intubation group showed a similar incidence of lung failure (17 vs. 14), kidney
      failure (6 vs. 2), and circulation failure (13 vs. 5). Except for two of the
      primarily nonintubated patients, all were intubated during their stay in the
      emergency room or on the intensive care unit. Days of ventilation (median, 7
      days) as well as the length of stay on the ICU (median, 11 days) were comparable
      in both groups. Mortality in the prehospital intubation group was not
      significantly different between groups (six vs. two deceased). CONCLUSION:
      Prognosis with respect to organ failure, treatment time, and mortality is not
      adversely affected in the German trauma system, if patients with severe thoracic
      trauma without manifest respiratory insufficiency and without other indications
      for intubation are not treated with prehospital intubation.

PMID- 11988654
TI  - Post hoc mortality analysis of the efficacy trial of diaspirin cross-linked
      hemoglobin in the treatment of severe traumatic hemorrhagic shock.
AB  - BACKGROUND: The efficacy trial of diaspirin cross-linked hemoglobin (DCLHb) in
      traumatic hemorrhagic shock demonstrated an unexpected mortality imbalance,
      prompting a three-step review to better understand the cause of this finding.
      METHODS: Patients were enrolled in this DCLHb hemorrhagic shock study using 28
      day mortality as the primary endpoint. Mortality data were primarily analyzed
      using the TRISS method and a nonblinded clinical review, followed by an
      independent Pennsylvania Trauma Outcome Study (PTOS)-derived probability of
      survival analyses. Finally, a trauma expert conducted a blinded clinical review
      of cases incorrectly predicted by these PTOS analyses. RESULTS: More of the DCLHb
      patients predicted to survive using TRISS actually died than in the control
      subgroup (24% vs. 3%, p < 0.002). Nonblinded clinical review noted that 72% of
      the patients who died had prior traumatic arrest, a presenting Glasgow Coma Scale
      score of 3, or a base deficit > 15 mEq/L. DCLHb patients predicted to survive
      using PTOS also more often died than did control patients (30% vs. 8%, p < 0.04).
      Blinded clinical review determined that 94% of the deaths were clinically
      justified. Both the TRISS and the PTOS models gave an adjusted mortality relative
      risk of 2.3, similar to the unadjusted risk data. CONCLUSION: Mortality analysis
      in this shock study involved both clinical case reviews and mortality prediction
      models. Despite the observation that nearly all of the deaths were clinically
      justified, the TRISS and PTOS models demonstrated excess unpredicted deaths in
      the DCLHb subgroup. A combined process, using both mortality prediction models
      and clinical case reviews, is useful in trauma studies that use a mortality
      endpoint.

PMID- 11988655
TI  - Antiplatelet therapy: an alternative to heparin for blunt carotid injury.
AB  - BACKGROUND: Blunt carotid injuries (BCIs) are uncommon. Most single-center
      studies are small and highlight the use of anticoagulation for treatment. In a
      retrospective review, we identified 22 patients who presented with BCI and
      assessed neurologic and survival outcomes on the basis of injury grade and
      treatment with anticoagulation or antiplatelet therapy. METHODS: Patient
      demographics were identified using the trauma registry at a single Level I trauma
      center. Chart reviews assessed neurologic function, modalities used for
      diagnosis, and treatment. Neurologic outcomes were graded good (minimal to no
      deficit), fair (moderate deficit needing some assistance), poor (requiring
      institutionalization), and dead. RESULTS: Twenty-two adult trauma patients were
      diagnosed with BCI, for an incidence of 0.45% in the 8-year study period. All BCI
      patients underwent head computed tomography and four-vessel cerebral
      arteriography. Eight patients were not anticoagulated, five because of
      intracranial injuries, two who had surgical CCA repairs, and one with an aortic
      injury. Full anticoagulation with heparin was attempted in seven patients, with
      four major bleeding complications requiring cessation of heparin and blood
      transfusions. Seven patients received antiplatelet therapy. No difference in
      neurologic outcome was observed between those receiving anticoagulation and those
      receiving antiplatelet therapy. Bleeding complications from full anticoagulation
      were higher than with antiplatelet agents (p = 0.05). CONCLUSION: Contrary to
      previous reports, we did not observe improved outcomes with full anticoagulation
      compared with antiplatelet therapy. Anticoagulation was associated with increased
      extracranial bleeding complications. The risks and possible benefits, as well as
      timing, of anticoagulation or antiplatelet therapy for BCI should be carefully
      weighed by the major care providers of the patient with multiple injuries.

PMID- 11988656
TI  - Routine prophylactic vena cava filtration is not indicated after acute spinal
      cord injury.
AB  - BACKGROUND: Acute spinal cord injury (SCI) is a devastating problem, with over
      10,000 new cases annually. Pulmonary embolism (PE) is a well-recognized risk in
      SCI patients, although no clear recommendations for prophylaxis exist. We
      therefore evaluated whether routine placement of prophylactic inferior vena cava
      filters is indicated in SCI patients. METHODS: The trauma registry of a regional
      trauma center was used to identify patients sustaining acute SCI resulting in
      tetraplegia or paraplegia after blunt or penetrating trauma for a 5-year period
      beginning in January 1995. Patients were analyzed for demographics, mechanism of
      injury, Injury Severity Score, associated long bone or pelvic fracture, severe
      closed-head injury, type of deep venous thrombosis (DVT) prophylaxis, level of
      SCI, and incidence of DVT and PE. DVT prophylaxis was performed in all patients
      with sequential compression devices (SCDs) when extremity fracture status
      permitted. Data are expressed as mean +/- SD and analyzed using Fisher's exact
      test. RESULTS: There were 8,269 admissions during the study period, with an
      overall incidence of DVT and PE of 11.8% and 0.9%, respectively. There were 111
      (1.3%) patients who sustained SCI, with an incidence of DVT and PE of 9.0% and
      1.8%, respectively, and no deaths. Of these 111 patients, 41.4% were paraplegics
      and 58.6% were tetraplegics, and 17.1% of patients had severe closed-head injury.
      Mean hospital length of stay was 23 +/- 20 days for SCI patients. Surveillance
      duplex ultrasound was performed an average of 2.3 +/- 2.1 times during each
      hospitalization. Mean Injury Severity Score was 30.0 +/- 12.2. The incidence of
      DVT and PE in those patients with SCDs alone was 7.1% and 2.3%; for SCDs plus
      subcutaneous heparin, the incidence was 11.1% and 2.8%; and for SCDs plus low
      molecular-weight heparin, the incidence was 7.4% and 0%, respectively, with no
      statistical difference between groups. The incidence of DVT in SCI patients with
      long bone fractures was 37.5%, which was significantly greater than the total SCI
      population (p < 0.02). CONCLUSION: The incidence of DVT and PE in SCI patients
      was similar to that of the overall trauma population when appropriate DVT
      prophylaxis was used. Subgroup analysis demonstrated that SCI associated with
      long bone fracture significantly increases the incidence of DVT. On the basis of
      the low incidence of PE in the present study, routine placement of prophylactic
      caval filters does not appear warranted in all SCI patients. However, SCI
      patients with long bone fractures, patients with DVT formation despite
      prophylactic anticoagulation, or patients with contraindications to
      anticoagulation may be appropriate candidates for prophylactic caval filtration.

PMID- 11988658
TI  - Isolated traumatic brain injury: age is an independent predictor of mortality and
      early outcome.
AB  - BACKGROUND: Geriatric trauma patients have a worse outcome than the young with
      comparable injuries. The contribution of traumatic brain injury (TBI) to this
      increased mortality is unknown and has been confounded by the presence of other
      injuries. The purpose of this study was to investigate the role of age in the
      mortality and early outcome from isolated TBI. METHODS: This was a retrospective
      analysis of all adult patients with isolated TBI (Abbreviated Injury Scale score
      > or = 3) admitted during a 5-year period to two Level I trauma centers.
      Mortality, Glasgow Outcome Scale score at discharge, therapy, and complications
      were compared for elderly (age > or = 65 years) and younger patients. RESULTS: Of
      694 patients, 22% were defined as elderly. The mortality for the elderly group
      was twice that of their younger counterparts (30% vs. 14%, p < 0.001), even for
      those with mild to moderate TBI (Glasgow Coma Scale score of 9-15). Thirteen
      percent of elderly survivors had a poor functional outcome (Glasgow Outcome Scale
      score of 2 or 3) at hospital discharge versus 5% in the young group (p < 0.01).
      Independent factors associated with a high mortality were age and Glasgow Coma
      Scale score. CONCLUSION: The mortality from TBI is higher in the geriatric
      population at all levels of head injury. In addition, functional outcome at
      hospital discharge is worse. Although some of this increased mortality may be
      explained by complications or type of head injury, age itself is an independent
      predictor for mortality in TBI.

PMID- 11988659
TI  - Chronic cocaine exposure alters carbon dioxide reactivity but does not affect
      cerebral blood flow autoregulation in anesthetized dogs.
AB  - BACKGROUND: Cocaine use is common in trauma victims. Consequently, understanding
      how cocaine alters normal physiology is important to providing appropriate
      medical care for these patients. This study was designed to identify how chronic
      cocaine exposure alters cerebrovascular physiology. METHODS: Ten dogs (seven
      experimental, three control) were studied. Transcranial Doppler was used to
      measure CO2 reactivity and autoregulation of cerebral blood flow velocity
      (CBFvel). Measurements were made in anesthetized animals (0.6% or 1.8% isoflurane
      in oxygen and intravenous fentanyl) at baseline before cocaine exposure and then
      at weekly intervals for 4 weeks. During the 4-week study period, cocaine was
      administered intravenously four times per day. RESULTS: Cocaine did not alter
      autoregulation of CBFvel in response to changes in mean arterial pressure.
      However, cocaine markedly impaired CO2 reactivity in three of the seven animals.
      In this subset of animals, increasing Paco2 decreased CBFvel, which is consistent
      with vasoconstriction rather than vasodilation. CONCLUSION: Chronic cocaine
      exposure does not alter autoregulation of CBFvel but does alter CO2 reactivity in
      a subset of susceptible animals. If confirmed in humans, these findings have
      implications for traumatic brain injury patients who are chronic cocaine users.
      Specifically, the findings suggest that hyperventilation could exacerbate
      intracranial hypertension in a subset of these patients.

PMID- 11988660
TI  - Risk factors for venous thromboembolism in pediatric trauma.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a major source of morbidity in
      critically ill trauma patients. Although the incidence and risk factors for VTE
      after trauma in adults have been well described, similar data regarding pediatric
      patients are lacking. METHODS: Pediatric (age < 16 years) trauma patients with
      VTE were identified from a large administrative database collated from 19 states
      across the United States. Risk factors for VTE were identified using multivariate
      techniques. RESULTS: Risk of VTE increased with age and Injury Severity Scores.
      VTE was clearly associated with head, thoracic, abdominal, lower extremity, and
      spinal injuries. Craniotomy, laparotomy, and spinal operations were also
      associated with VTE. The greatest risk of VTE was in children with venous
      catheters. CONCLUSION: Older children with high Injury Severity Scores, major
      vascular injury, craniotomy, or venous catheters are at risk for VTE. These data
      may help guide strategies geared toward screening and prophylaxis in injured
      children.

PMID- 11988661
TI  - Blunt renal trauma in children: experience with conservative management at a
      pediatric trauma center.
AB  - BACKGROUND: The authors reviewed the outcome for children with blunt renal injury
      managed with a nonoperative protocol at their pediatric trauma center. METHODS:
      Fifty-five consecutive children aged 0.5 to 17 years with blunt renal injury
      managed over a 14-year period were reviewed. All patients were evaluated with
      computed tomographic scanning. Injuries were graded according to the American
      Association for the Surgery of Trauma Organ Injury Scale. RESULTS: Forty-eight of
      55 children (87%) were successfully managed nonoperatively. Overall, there were 5
      grade I, 13 grade II, 18 grade III, 14 grade IV, and 5 grade V injuries. All
      children with grades I and III injuries were successfully managed nonoperatively.
      Two (6%) of these children required transfusion. Only four (29%) children with
      grade IV and three (60%) with grade V injuries required surgical interventions
      (one nephrostomy, six nephrectomies). Excluding patients with continuing
      hemorrhage, only 2 (14%) of 14 with high-grade injuries required surgical
      intervention (1 nephrostomy, 1 nephrectomy). Clearance of gross hematuria
      correlated with severity of injury and was prolonged in grade IV and V compared
      with grade I to III injuries (6.8 +/- 2.7 vs. 3.2 +/- 2.1 days, respectively; p <
      0.05). Fifty-one children (93%) available for follow-up were normotensive with
      normal renal function. CONCLUSION: These data support the use of conservative
      management for all grades in stable children with blunt renal injury. Transfusion
      requirements, operative rates, and outcome are consistent with other pediatric
      solid organ injuries.

PMID- 11988662
TI  - Enhanced guided bone regeneration with a resorbable chamber containing
      demineralized bone matrix.
AB  - BACKGROUND: The effectiveness of a nonporous poly-DL-lactide tubular chamber in
      guiding bone regeneration through a long bone defect had already been assessed in
      an experimental model using the rabbit radius. The injection of bone marrow stem
      cells into the chamber had proven to enhance bone regeneration. METHODS: The
      present study reports on the development of the above research project in a
      subsequent stage. Demineralized bone matrix (DBM) obtained by milling New Zealand
      rabbit femoral and tibial diaphyses was placed into a tubular chamber. A 10-mm
      defect was bilaterally created in the radii of 10 rabbits. On the left side
      (chamber side) the defect was treated by means of a poly-DL-lactide chamber
      filled with DBM, whereas DBM alone was used on the right side (control). RESULTS:
      Controls were performed at 3 and 6 months by radiographs and histomorphometry and
      demonstrated better bone growth on the chamber side versus the control side. A
      comparison with the results previously obtained by stem cell injection into the
      chamber revealed significant acceleration of bone regrowth in the first 3 months
      because of the addition of DBM to the chamber. However, no significant difference
      was found between the two sides after 6 months. CONCLUSION: These results have
      confirmed the effectiveness of the chamber as a container for the factors
      promoting bone regeneration, probably because the osteogenetic activity is
      maintained in situ.

PMID- 11988663
TI  - Arthroscopic reconstruction of the posterior cruciate ligament with quadruple
      hamstring tendon graft: a double fixation method.
AB  - BACKGROUND: Surgical reconstruction is indicated for posterior cruciate ligament
      (PCL) reconstruction for a grade III or IV injury, combined ligament or meniscus
      injuries, and chronic symptomatic posterior instability. Considerable controversy
      continues over the choice of graft tissues. Hamstring tendon has been popular in
      recent years. The purpose of this study is to prospectively assess the outcomes
      of PCL reconstruction using quadruple hamstring tendon autograft with a double
      fixation technique at minimal 2-year follow-up. METHODS: Only patients who
      received PCL reconstruction without combined associated posterolateral injury
      reconstruction were included in the series. A hamstring tendon graft is composed
      of a quadruple-stranded semitendinosus tendon and gracilis tendon 10 cm in
      length. An arthroscopic technique using a two-incision method and a double
      fixation technique were used. Clinical assessments were performed for 30
      patients, of which 27 were available for final outcome analysis. Clinical review
      of patients included the Lysholm knee scores, International Knee Documentation
      Committee (IKDC) scores, thigh muscle assessment, and radiographic evaluation.
      RESULTS: On the Lysholm knee rating, 89% of the patients demonstrated good or
      excellent results in the final assessment. In the IKDC rating analyses, 56% of
      the patients revealed 3- to 5-mm ligament laxity. Four patients (15%) had grade
      II laxity. For the IKDC final rating, 26% were normal and 55% were nearly normal.
      Seventy-eight percent of the patients had less than a 10-mm difference in thigh
      girth between their reconstructed and opposite limbs. CONCLUSION: Arthroscopic
      PCL reconstruction with quadruple hamstring tendon autograft appears to produce
      acceptable results at a minimal 2-year follow-up. The four-stranded hamstring
      tendon graft is adequate in graft size and associated with minimal harvesting
      morbidity. The double-fixation method for the graft could provide a rigid
      fixation. We believe that this technique could afford good ligament function
      after reconstruction and could be a reasonably acceptable choice for PCL injury.

PMID- 11988664
TI  - Open reduction and internal fixation of displaced intra-articular fractures of
      the calcaneus.
AB  - BACKGROUND: Thirty-two displaced intra-articular fractures of the calcaneus in 30
      patients were treated with open reduction and internal fixation. Fracture
      classification was based on Sanders computed tomographic classification. There
      were 18 type II fractures, 10 type III fractures, and 4 type IV fractures.
      METHODS: The operations were performed using a standard extended lateral
      approach, and the fractures were fixed with small-fragment AO T-plates without
      bone grafting. Average follow-up was 35.4 months (range, 24-53 months). The
      Creighton-Nebraska Health Foundation Assessment score for fractures of the
      calcaneus was used for evaluation. RESULTS: The average score was 86.7 for type
      II, 82.3 for type III, and 59.2 for type IV fractures. There was a clear
      statistically significant superiority with type II and type III fractures treated
      with open reduction when compared with type IV fractures (p < 0.0001).
      CONCLUSION: On the basis of our result, we recommend that type II and type III
      fractures be treated with open reduction and internal fixation. Despite the
      results of type IV fractures being significantly worse than that of type II and
      type III fractures, we recommend open reduction and internal fixation for type IV
      fractures to restore the hindfoot architecture and the subtalar joint, if
      possible. When the disrupted subtalar joint is so comminuted that it is beyond
      the surgeon's ability to reconstruct, primary subtalar arthrodesis should be
      performed in addition to open reduction and internal fixation.

PMID- 11988665
TI  - Does endotoxin-activated complement alter myocellular sodium homeostasis during
      sepsis?
AB  - BACKGROUND: Inappropriate complement activation is closely related to tissue
      injury and organ dysfunction during systemic infection. It is not clear, however,
      if endotoxin-induced complement activation is responsible for changes in
      myocellular sodium homeostasis during sepsis. METHODS: Rats underwent cecal
      ligation and puncture (CLP) or sham operation. Twenty-four hours after operation,
      fast-twitch extensor digitorum longus (EDL) muscles were isolated, incubated at
      30 degrees C for 1 hour in Krebs-Henseleit buffer (KHB) (pH 7.4), and used to
      measure intracellular Na+ and K+ contents. Blood samples were collected to
      measure serum hemolytic complement activity and endotoxin levels. In addition,
      EDL muscles isolated from normal animals were incubated at 30 degrees C for 1
      hour with zymosan-activated (10 mg/mL at 37 degrees C for 1 hour) rat sera, with
      lipopolysaccharide (LPS)-activated (LPS from Escherichia coli 055:B5, 10 or 200
      microg/mL at 37 degrees C for 30 minutes) rat sera, with heat-inactivated (56
      degrees C for 30 minutes) rat sera, with LPS (1 or 20 microg/mL), or in KHB. EDL
      muscles isolated from normal animals were also incubated with septic sera
      collected 6 or 24 hours after CLP with or without administration of soluble
      complement receptor type 1 (20 mg/kg, intraperitoneally). Myocellular Na+ and K+
      contents ([Na+]i and [K+]i) were assayed using "washout" technique. Soluble C5b-9
      complex levels in zymosan-activated or LPS-activated human sera were determined
      by enzyme-linked immunosorbent assay to evaluate the degree of complement
      activation induced by zymosan or LPS. RESULTS: Myocellular [Na+]i and
      [Na+]i/[K+]i ratios increased significantly 24 hours after CLP as compared with
      sham operation and were associated with decreased serum hemolytic complement
      activity and increased serum endotoxin levels. Zymosan-activated rat sera at
      sublytic concentrations markedly increased [Na+]i and [Na+]i/[K+]i ratios in
      isolated EDL muscles relative to heat-inactivated rat sera. LPS-activated rat
      sera, however, did not alter these two indices. In addition, myocellular [Na+]i
      and [Na+]i/[K+]i ratios were equivalent among normal EDL muscles incubated with
      septic sera, soluble complement receptor type 1-treated septic sera, or KHB.
      CONCLUSION: These results collectively suggest that polymicrobial sepsis, as
      produced by CLP, alters sodium homeostasis in fast-twitch skeletal muscles in
      association with changes in systemic complement activation and circulating
      endotoxin levels. Although endotoxin can activate the complement cascade,
      endotoxin-induced complement activation does not appear to be responsible for
      changes in myocellular sodium homeostasis observed during sepsis in rats.

PMID- 11988667
TI  - A trial of the effectiveness of artificial dermis in the treatment of patients
      with burns greater than 45% total body surface area.

PMID- 11988666
TI  - Association between injury pattern of patients with multiple injuries and
      circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and
      interleukin-10, and polymorphonuclear neutrophil elastase.
AB  - BACKGROUND: Our knowledge about the bidirectional interactions between brain and
      whole organism after trauma is still limited. It was the purpose of this
      prospective clinical study to determine the influence of severe head trauma (SHT)
      as well as trauma in different anatomic injury regions on posttraumatic
      inflammatory mediator levels from patients with multiple injuries. METHODS:
      Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with
      multiple injuries without SHT, and 45 patients with both SHT and multiple
      injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis
      factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear
      neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay
      technique. The influence of head injuries as well as thorax, abdomen, and
      extremity injuries on the mediator release from patients with multiple injuries
      was investigated by multivariate linear regression models. RESULTS: The soluble
      tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3
      hours of trauma in all three injury groups and returned to reference ratios after
      12 hours. The lowest increase was found in patients suffering from an isolated
      SHT. Lowest mediator levels in this patient population were also found for IL-6,
      IL-10, and PMN elastase during the first 36 hours after trauma. Additional
      injuries to the head, thorax, abdomen, and extremity modulated mediator levels to
      a different degree. No specific effect was found for SHT when compared with other
      injury groups. Thorax injuries caused the quickest rise in mediator levels,
      whereas abdominal injuries significantly increased PMN elastase levels 12 to 24
      hours after trauma. CONCLUSION: Traumatic injuries cause the liberation of
      various mediators, without any specific association between anatomic injury
      pattern and the pattern of mediator release.

PMID- 11988668
TI  - Successful healing of a blunt duodenal rupture by nonoperative management.

PMID- 11988669
TI  - The abdominal compartment syndrome complicating nonoperative management of major
      blunt liver injuries: recognition and treatment using multimodality therapy.

PMID- 11988670
TI  - Total necrosis of the pancreas and renal cortex secondary to hypothermia therapy.

PMID- 11988671
TI  - Early- and late-onset atrioventricular valve rupture after blunt chest trauma:
      the usefulness of transesophageal echocardiography.

PMID- 11988672
TI  - Treatment of life-threatening subcutaneous hemorrhage after severe blunt trauma
      by transcatheter arterial embolization.

PMID- 11988673
TI  - Massive bleeding caused by rupture of intra-abdominal testicular seminoma: case
      report.

PMID- 11988674
TI  - Blunt injury of the innominate artery associated with a bovine arch.

PMID- 11988675
TI  - Inverse intubation: potential for complications.

PMID- 11988678
TI  - The development of the gastric CO2 gap in the first 48 hours after severe burn
      injury.

PMID- 11988679
TI  - Staged primary closure of the open abdomen.

PMID- 11988680
TI  - [Anhidrotic ectodermal dysplasia and Incontinentia pigmenti: pieces of the same
      puzzle].

PMID- 11988681
TI  - [Obesity persistent scleredema: study of 49 cases].
AB  - BACKGROUND: Buschke sclerodema is a very rare disease. Our objective was to show
      that persistent scleredema is frequent in certain group of patients at risk.
      PATIENTS AND METHODS: We studied 49 patients, diagnosed between 1995 and 1999 in
      dermatology, pneumology and endocrinology departments in Martinique. Diagnosis
      was performed on classical clinical and histopathological aspects of sclerodema.
      Data studied were age, sex, mode of occurrence, clinical and histopathological
      aspects and associated diseases. RESULTS: The 49 patients presented with
      cutaneous infiltration of the upper part of the trunk, with thick dermis and
      large collagen bundles on histopathological examination. Forty-two had mucoid
      substance deposition, stained with Alcian Blue (this criteria was considered as
      inconstant by most authors in the literature). Sex ratio H/F was 0.06 (93 p. 100
      females). Mediam age at onset was 50 years ranging from 20 to 79 years. The
      occurrence was insidious in 97 p. 100 of cases. All patients had neck and nuchae
      involvement. The disease involved the back in 93 p. 100, upper limbs in 50 p. 100
      and lower limbs and face in 43 p. 100 of patients. Fifty-six percent of patients
      had limitation of shoulder movements, 16 p. 100 limitation of mouth opening, 20
      p. 100 limitation of eyelid opening, 36 p. 100 had myalgia, 73 p. 100 had
      pruritus and 66 p. 100 had dyspnea. Obesity was present in 95 p. 100, diabetes in
      79.5 p. 100, elevated blood pressure in 81.5 p. 100 and monoclonal
      dysglobulinemia in 46 p. 100 of patients. Twenty-five patients had a
      polysomnography showing severe obstructive sleep apnea syndrome. DISCUSSION: The
      large number of patients in our study can be explained by the search for
      sclerodema in patients with obesity, diabetes and high blood pressure. The
      disease is usually unknown by patients and physicians unless a systematic
      examination is performed. Association with obstructive sleep apnea syndrome was
      not previously reported and a larger study is ongoing.

PMID- 11988682
TI  - [Profuse scabies: kinetic curves of parasitologic cure with an association of
      benzyl benzoate and sulfiram].
AB  - BACKGROUND: In vitro exposure to benzyl benzoate (25 p. 100) kills Sarcoptes
      scabiei within three hours. The aim of our study was to determine in vivo
      elimination of Sarcopte scabiei with a benzyl benzoate-sulfiram association.
      METHODS: Medical charts of patients hospitalized for disseminated scabies from
      1993 to 1999 were reviewed retrospectively. The diagnosis of scabies was
      confirmed by microscopic determination. Parasitological examinations were
      conducted every day or every two days until negative results. Patients were
      treated by successive applications of benzyl benzoate until parasitological cure.
      RESULTS: Twenty patients were included in the study. The median delay of
      parasitological cure was seven days. After 15 days, 95 p. 100 of patients were
      cured. Two cutaneous side-effects were reported. DISCUSSION: Despite immediate in
      vitro efficacy, benzyl benzoate action is delayed in vivo. The time of
      parasitological negativation after one application of benzyl benzoate is unknown.
      Therefore, it is not currently possible to determine whether our therapeutic
      regimen was excessive or not.

PMID- 11988683
TI  - [Risk factors for cutaneous wart onset in transplant recipients].
AB  - INTRODUCTION: Transplant recipients are at increased risk for cutaneous warts. We
      have investigated the delay of their onset warts and some possible risk factors
      for their occurrence. PATIENTS AND METHODS: Clinical data were summarized on a
      standard question and examination sheet. Warts were diagnosed on clinical grounds
      and course duration assessed on patients' report. Immunosuppressive therapy and
      HLA group were collected from clinical transplantation records. An actuarial
      curve was used to evaluate the delay of onset of warts. To compare associated
      risk factors among the two groups (patients with warts and patients without
      warts) at 1 year and 3 years following transplant, single variate analysis was
      performed. RESULTS: At the time of transplant, the prevalence of warts was 16 p.
      100. It was increased with the duration of immunosuppression: 23 p. 100 at 1
      year, 35 p. 100 at 3 years, 45 p. 100 at 5 years and 54 p. 100 at 7 years. Warts
      were multiple and principally localized on the hands. Transplant recipients
      without cutaneous warts 3 years after transplant had less intensive
      immunosuppressive therapy than the group with cutaneous warts. No association was
      found between age, sex, HLA markers, actinic keratosis and wart onset.
      DISCUSSION: The prevalence of warts increases with the duration of
      transplantation. Cutaneous warts are generally multiple and have a chronical
      course without spontaneous remission. More intensive immunosuppressive therapy
      increases their occurrence. This trial cannot evaluate the association between
      carcinoma and warts. On the basis of our study, there is no relationship between
      actinic keratosis and warts, nor HLA markers and warts.

PMID- 11988684
TI  - [Acute generalized exanthematous pustulosis due to fluconazole].
AB  - INTRODUCTION: Fluconazole (Triflucan(R)), a systemic triazole antifungal agent is
      largely prescribed and some cutaneous side effects have already been described.
      We report the first case of acute generalized exanthematous pustulosis due to
      this molecule in a patient with cutaneous candidosis. CASE REPORT: A 65 year-old
      woman was treated with fluconazole (200 mg/day) for a persistent cutaneous
      candidosis infection on the buttocks. After the third dose, the patient presented
      with a pustular eruption with erythema located on her trunk and in her large skin
      folds. The eruption was associated with fever at 39 degrees C, asthenia and
      neutrophilia (9,000/mm(3)). The histologic examination and the negativity of
      microbiological cultures were consistent with the diagnosis of acute generalized
      exanthematous pustulosis. The eruption cleared with local steroids in about ten
      days. Nineteen days later, the same pustular eruption occurred but without fever
      nor neutrophilia. DISCUSSION: Clinical, biological and histological
      manifestations were consistent with the diagnosis of acute generalized
      exanthematous pustulosis due to fluconazole. According to the imputability
      criteria of Begaud et al., intrinsic imputability of fluconazole was possible
      (I2). According to the classification of the EuroSCAR study, it was certain. No
      similar case of recurrence had already been described after the withdrawal of the
      molecule. We believe this is the first case of acute generalized exanthematous
      pustulosis due to fluconazole (extrinsic imputability: B0).

PMID- 11988685
TI  - [Bullous amyloidosis].
AB  - INTRODUCTION: The occurrence of skin damage during systemic amyloidosis is
      common, but the appearance of bullous lesions is rare. Only twenty-seven cases
      have been reported in the literature. We report our observation of bullous
      amyloidosis during progression of renal amyloidosis. OBSERVATION: A 61 year-old
      man, presented with white, soft, palpebral edemas of the lower limbs, without
      scutulum involvement, associated with a large cubital nerve that had appeared in
      March 1997. Biological explorations revealed a nephrotic syndrome. Pathologic
      study of the renal biopsy concluded in amyloidosis. Treatment with colchinine
      stabilized the renal damage. One year later, a non-pruriginous, papular and
      bullous eruption occurred, localized essentially in the axillary and inguinal
      crural folds of the forearms and legs. In the presence of an amyloidal deposit
      and intra-epidermal detachment, the cutaneous biopsy was evocative of bullous
      amyloidosis. The search for concomitant myeloma was negative. Treatment with
      colchinine was effective. The bullous lesions disappeared after 2 months, and 21
      months later, renal damage was still stable. DISCUSSION: These particularities in
      evolution are exceptional and have never been described. A hypothetical
      modification in the physico-chemical properties of the amyloidal protein might
      explain the bullous eruption and stabilization of renal damage.

PMID- 11988686
TI  - [Anisakis simplex and immediate hypersensitivity reactions].
AB  - BACKGROUND: Anisakis simplex is one of the nematode worms that parasitize sea
      mammals. When its larvae are accidentally ingested by humans, they can infect the
      host, resulting in anisakiasis manifested by digestive symptoms, or they may
      cause an allergic reaction, which in some cases may be severe. CASE REPORTS: We
      report three cases of acute urticaria associated with abdominal pain, and
      hypotension in two of them, starting two to six hours after ingestion of raw
      fish. The diagnosis of an allergic reaction caused by Anisakis simplex was based
      on the clinical histories and positive tests for anisakis-specific IgE.
      DISCUSSION: In patients with acute urticaria associated with abdominal symptoms,
      a history of ingestion of raw fish in the preceeding hours is evocative of gastro
      allergic anisakiasis. In association with symptomatic treatment, gastrointestinal
      endoscopy allows the larvae to be visualized and removed, which may relieve the
      symptoms and provide a diagnosis before the results of skin testing and
      serological assay are known.

PMID- 11988687
TI  - [Cerebellar, pulmonary and cutaneous localizations of juvenile xanthogranuloma].
AB  - BACKGROUND: Juvenile xanthogranuloma is one of the most common non-langerhan cell
      histiocytoses in children. Usually cutaneous, there are disseminated forms.
      However, neurological localizations remain exceptional. CASE REPORT: We report
      the case of a cerebellar localization, associated with cutaneous and pulmonary
      lesions in a 13-month old child. Surgical treatment of the cerebellar lesion was
      associated with vinblastin chemotherapy, that led to total regression of the
      cutaneous and pulmonary lesions, neurological stabilization, without recurrence
      on the control IRM, after a period of 7 years. DISCUSSION: This is the second
      reported case of histologically documented cerebellar juvenile xanthogranuloma.
      In the event of cutaneous juvenile xanthogranuloma, the neurological examination
      must be attentive and supplemented, in case of any suspicion, by medical imaging.
      We believe that surgical treatment of neurological juvenile xanthogranuloma is
      necessary, in the event of symptomatic lesions and accessible to surgery. No
      consensus has been reached on subsequent treatments (radiotherapy, chemotherapy)
      and must be discussed according to the clinical profile and data in the
      literature.

PMID- 11988688
TI  - [Cutaneous localization of multiple myeloma on the tract of a central venous
      catheter].
AB  - INTRODUCTION: Extramedullary plasmocytoma are plasmocytic tumours developing
      outside of the bone marrow. Cutaneous localization of extramedullary plasmocytoma
      are rare and can be primitive or secondary. We report two cases of secondary
      extramedullary plasmocytoma occurring on central venous catheterization sites.
      OBSERVATIONS: A 68 year-old woman and a 69 year-old man presented with
      subcutaneous metastases located along the tracts of central venous catheters or
      implantable ports, which were either still on site or removed recently. Although
      the patients initially responded to melphalan therapy, they eventually died of
      multiple myeloma a few weeks following the diagnosis of the cutaneous
      localizations. DISCUSSION: Extramedullary plasmocytoma are most commonly found in
      the upper respiratory tract, the gut and the lymph, but cutaneous localization is
      rare. We report two cases of cutaneous extramedullary plasmocytoma located on the
      tract of central intravenous infusion sites. Both patients were treated with
      melphalan with initial improvement, followed by an early relapse. Two cases of
      myeloma metastases occurring on the tract of central venous catheters have
      previously been published. This localization seems to occur late in the course of
      this disease and to be associated with a poor prognosis.

PMID- 11988689
TI  - [Acquired haemophilia in a patient with systemic lupus erythematosus].
AB  - INTRODUCTION: In patients with lupus, the most common acquired circulating
      anticoagulant is antiprothrombinase which is responsible for thrombosis. The
      presence of antibodies directed against factor VIII is rarely found in systemic
      lupus erythematosus. A case of acquired haemophilia in a patient with lupus is
      reported. CASE REPORT: A 30 year-old woman with systemic lupus erythematosus
      developed a right coxalgia and ecchymotic skin lesions which were prominent on
      the right arm and forearm. Laboratory values were as follows: positive
      antinuclear antibodies > 1: 2 560, anti-DNA antibodies (300 IU/ml), prolonged
      activated partial thromboplastin time, reduced factor VIII activity (1 p. 100)
      and the presence of antibodies against factor VIII. Magnetic nuclear resonance of
      the right hip confirmed the presence of an intramuscular hematoma. The patient
      was initially treated with intravenous pulse and oral corticosteroids,
      intravenous immunoglobulins and intravenous cyclophosphamide. Clinical and
      biological improvement was promptly obtained. DISCUSSION: In our patient with
      systemic lupus erythematosus, bleeding revealed acquired haemophilia with
      antibodies against factor VIII. It should be pointed out that the association
      between lupus and haemophilia is uncommon and that at present no standardized
      treatment can be recommended.

PMID- 11988690
TI  - [Intravascular large cell lymphoma revealed by diffuse telangiectasia and cauda
      equina syndrome].
AB  - BACKGROUND: Intravascular lymphoma is a rare disease with usually fatal outcome,
      characterized by the proliferation within the lumen of small blood vessels of
      neoplastic large lymphoid cells of B-cell origin. We report a case of
      intravascular lymphoma revealed by diffuse telangiectasia and cauda equina
      syndrome. CASE REPORT: A 64-year-old Vietnamese woman presented with unexpected
      fever and weight loss. Three months after the onset of the first symptoms, an
      oedema appeared on the lower limbs and the trunk, followed by the eruption of
      diffuse superficial telangiectasia. Neurologic examination revealed a cauda
      equina syndrome. The diagnosis of intravascular B cell lymphoma was established
      on cutaneous and muscular biopsy specimen. A moderate hemophagocytic syndrome was
      observed, confirmed by bone marrow biopsy. Corticosteroid therapy was started,
      followed by combination chemotherapy yielding complete response. Six months later
      death occurred, without evidence of relapse of intravascular lymphoma.
      DISCUSSION: Clinical presentation of intravascular lymphoma is often confusing,
      mimicking systemic disease, with a predilection for skin and nervous system
      involvement. Diagnosis is difficult and often an autopsy finding. Prognosis is
      generally poor, but favourable responses to chemotherapy have been observed after
      early diagnosis and treatment. The pathogenesis of intravascular lymphoma remains
      unknown. Dysfunction of cell-endothelial interaction affecting adhesion molecules
      has been suspected. The implication of Epstein-Barr virus in intravascular
      lymphoma remains controversial.

PMID- 11988691
TI  - [Rapp Hodgkin's syndrome: folliculitis of the scalp cured with zinc oxide salts].

PMID- 11988692
TI  - [Resolving the problem of a case of bromine intoxication].

PMID- 11988693
TI  - [The hair of cancer patients].

PMID- 11988694
TI  - [Shouldn't the "journee de depistage" evolve towards a "journee de prevention"?].

PMID- 11988696
TI  - [Genital pustules and skin papules].

PMID- 11988697
TI  - [Febrile exanthema and polyadenopathy].

PMID- 11988698
TI  - [Tumefaction of a finger].

PMID- 11988699
TI  - [Periodic Fever].

PMID- 11988700
TI  - [Diagnosis of a white lesion of the mouth].

PMID- 11988701
TI  - [Hypersensitivity to corticosteroids].

PMID- 11988702
TI  - [Hypersensitivity to tixocortol pivalate].

PMID- 11988703
TI  - [Vulvar Paget's disease].

PMID- 11988704
TI  - [Combined capillary and lymphatic malformations].

PMID- 11988705
TI  - [Paget's bone disease: a rare cause of leg ulcers].

PMID- 11988706
TI  - [Thrombocytosis induced by low-dose isotretinoin (Roaccutane(R))].

PMID- 11988707
TI  - Severity-of-illness markers as predictors of nosocomial infection in adult
      intensive care unit patients.
AB  - BACKGROUND: Patients admitted to intensive care units (ICUs) are at high risk for
      acquiring nosocomial infections. We examined the association between markers of
      severity of illness at ICU admission and the development of ICU-attributable
      nosocomial infections. METHODS: Retrospective cohort study of 851 patients
      admitted to the medical or surgical ICU in an urban teaching hospital from
      January 1997 to January 1998. Logistic regression analysis was used to identify
      predictors of nosocomial infection, including the Acute Physiology, Age, Chronic
      Health Evaluation III severity-of-illness scoring system. RESULTS: Patients
      receiving mechanical ventilation on day 1 of ICU admission (OR, 1.99; 95% CI,
      1.29-3.06) and patients transferred to the ICU from another unit within the same
      hospital (OR, 2.04; 95% CI, 1.24-3.34) were twice as likely to acquire an ICU
      attributable nosocomial infection compared with patients admitted from other
      sources. The day-1 Acute Physiology, Age, Chronic Health Evaluation III score was
      not a significant predictor of nosocomial infection. CONCLUSION: The need for
      mechanical ventilation on ICU day 1 and transfer to the ICU from another unit are
      independent predictors of ICU-attributable nosocomial infections. Up to 50% of
      ICU patients who develop nosocomial infections could be easily identified at ICU
      admission, allowing for targeted use of preventive strategies to reduce the risk
      of nosocomial infections.

PMID- 11988708
TI  - A systematic audit of economic evidence linking nosocomial infections and
      infection control interventions: 1990-2000.
AB  - BACKGROUND: Nosocomial infections (NIs) are a serious patient safety issue.
      Infection control personnel are responsible for implementing interventions to
      reduce this risk. The purpose of this systematic review was to audit the
      published economic evidence of the attributable cost of NIs and interventions
      conducted by infection control professionals and to evaluate the methods used.
      Economic evaluation methodology and recommendations for standardization are
      reviewed. METHODS: A search of MEDLINE and HealthSTAR with medical subject
      headings or text words "nosocomial infections," "infection control," or "hospital
      acquired infections" cross-referenced with "costs," "cost analysis," "economics,"
      or "cost-effectiveness analysis" was conducted. Published review articles were
      also searched. Inclusion criteria included articles published between 1990 and
      2000 that contained an abstract and original cost estimate and were written in
      English. Results were standardized into a common currency. RESULTS: Fifty-five
      studies were eligible. Approximately one quarter examined NIs in intensive care
      patients (n = 13). Most studies were conducted from the hospital perspective (n =
      48). The costs attributable to bloodstream (mean = $38,703) and methicillin
      resistant Staphylococcus aureus infections (mean = $35,367) were the largest.
      CONCLUSIONS: Increased standardization and rigor are needed. Clinicians should
      partner with economists and policy analysts to expand and improve the economic
      evidence available to reduce hospital complications such as NI and other adverse
      patient/staff outcomes.

PMID- 11988709
TI  - Biologic monitoring of dental office sterilizers in Mexico.
AB  - BACKGROUND: Biologic indicators (BIs) are the quality control applicable to
      sterilization cycles, but their use was not previously taught in Mexican dental
      schools or recommended by professional associations. A Mexican official standard,
      the Mexican Official Norm, published by health authorities in 1999 makes it
      compulsory for dentists to biologically verify sterilization cycles. However,
      only a few dentists comply because the use of BIs is largely unknown and the
      standard is not being enforced. OBJECTIVE: To evaluate the incidence of
      sterilization failures in a convenience sample of dental offices in Mexico.
      METHODS: Spore strips were distributed to dentists interested in using this
      service. The dentists mailed the processed BIs to the laboratory for culture.
      RESULTS: In 6 years, 3277 tests were submitted from 82 dental offices. Thirty
      four offices (41%) submitted 1 to 12 tests, 22 (27%) sent 14 to 48 tests, 18
      (22%) mailed 49 to 96 tests, and 8 (10%) sent >97 tests. The sterilization
      methods were steam (74.4%), dry heat (20%), and chemical vapor (5.6%). A total of
      242 sterilization failures (7.4% of all cycles) were detected. Convection dry
      heat failed with a greater frequency with chi(2) analysis (chi(2) = 13.71, P
      =.0175). CONCLUSIONS: Sterilization failures occurred in instrument loads used in
      patient treatment. Steam and chemical vapor under pressure failed less often than
      convection dry heat. When corrective action is taken, routine use of BIs
      increases patient safety.

PMID- 11988710
TI  - Hospital-acquired meningitis in patients undergoing craniotomy: incidence,
      evolution, and risk factors.
AB  - OBJECTIVES: To establish the incidence of postcraniotomy meningitis, identify
      etiologic agents, assess patients' medical progress in relation to both length of
      hospitalization and mortality, and analyze risk factors. MATERIAL AND METHODS:
      This study was developed at Hospital Sao Paulo, a tertiary university hospital,
      between August 1995 and January 1998. We conducted a case-control trial, in which
      50 pairs of patients were matched. RESULTS: An 8.9%-postcraniotomy meningitis
      incidence was found. Gram-negative bacilli were the most common etiologic agents
      isolated. Mortality among the patients was 30%. Mean hospital stay for the
      patients was 42.9 +/- 22.1 days; for the controls, mean hospital stay was 19.0 +/
      11.4 days (P =.00001). Although several risk factors were identified by
      univariate analysis, including postoperative external ventricular shunt (OR =
      2.92, CI 95% = 1.245-6.865, P =.014), remote site infection (OR = 2.85, CI 95% =
      0.995-8.173, P =.051), and repeat operation (OR = 5.02, CI 95% = 1.569-16.066, P
      =.007), only repeat operation remained in the multivariate analysis model (OR =
      3.68, CI 95% = 1.158-11.700, P =.027). CONCLUSION: Postcraniotomy meningitis
      resulted in a high mortality rate and a longer hospital stay, with repeat
      operation identified among the risk factors.

PMID- 11988711
TI  - Measles antibody prevalence rates among young adults in Israel.
AB  - BACKGROUND: In Israel, vaccination coverage against measles is high, yet
      seroepidemiologic studies have shown that more than 15% of the 18-year-old
      population were unprotected against the disease. A 2-dose program of vaccination
      against measles, mumps, and rubella at the ages of 1 and 6 years was begun in
      1990, supplemented by a measles catch-up plan for all 13-year-olds. The aim of
      this study was to assess the prevalence of antimeasles antibodies at induction to
      the Israel Defense Forces in the first doubly vaccinated birth-cohort. METHODS:
      In 1996, serum samples of 540 recruits, 339 men and 201 women, were tested for
      measles virus antibody. Findings were compared with surveys conducted in 1987 and
      1990. RESULTS: Measles antibodies were present in 95.6% (95% CI, 93.5-97.1) of
      the recruits. Antibody prevalence was higher in women than in men (99% vs 93.5%;
      P =.0096). A slightly lower seroprevalence was found in recruits born in the
      former Soviet Union. The results were substantially higher than the
      seroprevalence rates found in 1987 (73.3%) and 1990 (84.6%). CONCLUSIONS: The
      high prevalence of antimeasles antibodies in the young adult population in Israel
      points to the success of the double-vaccination policy in promoting immunity
      against the disease.

PMID- 11988712
TI  - Nosocomial transmission of methicillin-resistant Staphylococcus aureus from a
      mother to her preterm quadruplet infants.
AB  - BACKGROUND: Patient-to-patient transmission of methicillin-resistant
      Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs) has been
      well described. We report the first documented outbreak of probable transmission
      of MRSA from a mother to 3 of her preterm quadruplet infants postnatally.
      METHODS: Routine surveillance of clinical microbiologic laboratory reports
      revealed an increased incidence of MRSA infections in our NICU, including 3 of 4
      preterm quadruplets. Surveillance cultures of the anterior nares of all patients
      and the quadruplets' parents were performed to detect MRSA carriage. The isolates
      were typed by pulsed-field gel electrophoresis with the restriction endonuclease
      SmaI. Infection control strategies included mupirocin treatment and contact
      isolation precautions for infected/colonized infants. RESULTS: Clinical cultures
      from infants A, C, and D and surveillance cultures of the quadruplets' mother and
      2 additional unrelated infants grew the same clone of MRSA. The mother's only
      identified risk factors for MRSA acquisition were 2 prepartum hospitalizations
      related to the multiple gestation and previous treatment with antibiotics. All
      anterior nares cultures were negative for MRSA after mupirocin treatment.
      CONCLUSIONS: Use of gowns and gloves by the family members of women with multiple
      gestations should be recommended to prevent transmission of potential pathogens
      in the NICU.

PMID- 11988713
TI  - Expanding the infection control team: development of the infection control
      liaison position for the neonatal intensive care unit.
AB  - Neonatal survival has risen progressively during the past 30 years. As the limits
      of viability continue to decline, the challenges of providing care to infants at
      the lowest extremes of gestational age and birth weight continually increase.
      Nosocomial infections in this very fragile population can be devastating. The
      complexity of care of these premature infants requires specialized knowledge of
      the neonate, infectious disease processes, and methods to reduce infection risks
      in the neonatal intensive care unit. The role of infection control liaison has
      been established in our institution as an adjunct to meeting this challenge by
      providing a line of communication between staff, neonatologists, and the
      infection control team. This article describes the role of the infection control
      liaison and its overall impact on the infection control program in an 87-bed
      level II, III, and IV neonatal intensive care unit from 1995 to 1999.

PMID- 11988714
TI  - Contaminated operating room boots: the potential for infection.
AB  - BACKGROUND: Dirty operating room boots, often contaminated with blood and other
      infected material, are not only a source of discontent among surgeons and other
      surgical personnel, but they also pose a potential risk of transmission of viral
      or bacterial diseases to the wearer and cleaner of the boots. METHOD: Operating
      room boots were examined for the presence of blood by visual inspection; the
      presence or absence of blood was confirmed by a specific biochemical test.
      Bacterial isolation and quantification from boots were performed with
      conventional methodology. RESULTS: In this study, a spot check revealed that 44%
      of all operating room boots tested were contaminated with blood and that the
      majority were contaminated with bacteria. Sixty-three percent of surgeons using
      the facility had blood-contaminated boots, and a significant number of boots
      belonging to other surgical personnel were also contaminated with blood and
      bacteria normally associated with skin microbiota or the environment. Comfort
      shoes with perforations on their upper surface and plastic boots commonly found
      in operating rooms were most heavily contaminated, whereas Wellington boots and
      clogs had less contamination. CONCLUSION: The present practice of manual cleaning
      of boots is unsatisfactory, and it is recommended that boots be washed in
      automatic washing machines.

PMID- 11988715
TI  - Pseudo-outbreak of Mycobacterium fortuitum due to contaminated ice machines.
AB  - BACKGROUND: An almost 4-fold increase from normal baseline levels in the
      isolation of Mycobacterium fortuitum from respiratory tract specimens was
      observed. The majority of these isolates were obtained from patients residing on
      1 of 2 wards, prompting an epidemiologic investigation. METHODS: In addition to
      patient specimens, environmental cultures were collected from various water
      sources on the 2 affected wards. Samples were also collected from uninvolved
      areas of the hospital. All specimens were cultured with use of a continuously
      monitored broth system for the isolation of mycobacteria. RESULTS: The
      respiratory tracts of 19 patients were colonized by M fortuitum. Surveillance
      cultures obtained from uninvolved areas of the hospital were either negative for
      mycobacteria or were colonized by M avium complex or M gordonae. Two ice
      machines, servicing the affected areas each, were colonized by M fortuitum in
      multiple cultures. CONCLUSIONS: The M fortuitum pseudo-outbreak was due to
      contaminated ice machines located on each of the affected units. After removal
      and replacement of the ice machines, the pseudo-outbreak resolved.

PMID- 11988716
TI  - Searching the health care literature efficiently: from clinical decision-making
      to continuing education.
AB  - Searching the health care literature is an activity in which infection control
      professionals must routinely engage to seek evidence-based answers to specific
      practice questions and to stay abreast of developments in the field. Without the
      appropriate tools, the tremendous volume of clinical literature makes both of
      these daunting tasks. In this article, we illustrate techniques for searching
      MEDLINE efficiently, both as a means of answering particular clinical questions
      and for generating periodic updates on topics of general interest. With use of a
      specific example relevant to infection control, we demonstrate the identification
      of appropriate Medical Subject Headings terms that capture a given question or
      topic and the development of effective searches with use of these terms. We also
      touch on the advantages of targeting systematic reviews and meta-analyses in
      searching for evidence and staying abreast of the literature in general.

PMID- 11988717
TI  - Pseudoepidemic from Mycobacterium gordonae due to a contaminated automatic
      bronchoscope washing machine.

PMID- 11988718
TI  - Testing for Creutzfeldt-Jakob disease.

PMID- 11988719
TI  - Arthroscopic versus open acromioplasty: a prospective, randomized, blinded study.
AB  - The purpose of this study is to determine whether arthroscopic acromioplasty is
      equivalent or superior to open acromioplasty, in a prospective, randomized,
      controlled, blinded clinical trial. Seventy-one patients with a clinical
      diagnosis of impingement syndrome were randomized to arthroscopic or open
      acromioplasty. Nine were excluded because of full-thickness rotator cuff tears
      diagnosed after randomization. Sixty-two patients (49 men and 13 women) with a
      minimum follow-up of 12 months (mean, 25 months) were included. The patient
      groups were virtually identical with regard to duration of symptoms, shoulder
      functional demands, age, sex, hand dominance, mechanism of onset, range of
      motion, strength, joint laxity, and the presence of a compensation claim.
      Patients were prospectively randomized to arthroscopic or open acromioplasty
      after stratification for age (>50 years),associated ligamentous laxity, and the
      presence of an ongoing compensation claim. The main outcome measure was visual
      analog scales for pain and function. Also recorded were UCLA shoulder scores and
      visual analog scales for postoperative improvement, patient satisfaction, and a
      variety of clinical measures. An independent blinded examiner assessed all
      patients. There was no significant difference between open and arthroscopic
      acromioplasty in visual analog scales for postoperative improvement (P =.30),
      patient satisfaction (P =.94), UCLA shoulder score (P =.69), or strength (P
      =.62); however, open was superior to arthroscopic acromioplasty for pain and
      function (P =.01). Overall, 67% of patients had a good or excellent result. This
      increased to 87% when unsettled compensation claims were excluded. Repeat (open)
      acromioplasty was performed in 5 patients in the unsuccessful arthroscopic group
      without improvement. Open acromioplasty was equivalent to arthroscopic
      acromioplasty for UCLA scores and patient satisfaction. For pain and function,
      both gave significant improvement but the open technique may be superior.
      Unsettled compensation is a predictor of poor outcome.

PMID- 11988720
TI  - The use of thermal capsulorrhaphy in the treatment of multidirectional
      instability.
AB  - The purpose of this study is to report on our experience with thermal
      capsulorrhaphy in the treatment of multidirectional instability of the shoulder.
      Thirty-three consecutive patients (33 shoulders) with multidirectional
      instability were treated with arthroscopic thermal capsulorrhaphy. Twelve
      patients had a history of traumatic dislocation. Three patients had been
      previously treated with open inferior capsular shift procedures. At a mean follow
      up of 36 months (range, 24-40 months), results were available for 30 patients. On
      the basis of the UCLA rating scale, out of a possible 35 points, the mean
      preoperative score was 16.7 points and postoperatively it was 30.1 points, with 3
      excellent, 20 good, and 7 poor results. Twenty-three patients (76%) were returned
      to full activity. In our experience the majority of patients with
      multidirectional instability were able to return to their previous occupations in
      the armed forces following thermal capsulorrhaphy. More information further
      defining the biomechanical pathology of capsular laxity and the specific role of
      electrothermal shrinkage in treating shoulder instability is needed.

PMID- 11988721
TI  - Shoulder arthroplasty for proximal humeral nonunions.
AB  - Between 1980 and 1997, 27 patients underwent shoulder arthroplasty because of
      pain or functional impairment due to a proximal humeral nonunion. Twenty-five of
      the 27 shoulders with a mean 6-year follow-up period (range, 2-15 years) were
      included in the study. There were 19 women and 6 men, with a mean age of 65
      years. The most frequent original fracture types were 2-part surgical neck (64%)
      and 3-part greater tuberosity fractures (28%). Twenty-one shoulders underwent
      hemiarthroplasty, and 4 underwent total shoulder arthroplasty. Shoulder
      arthroplasty resulted in significant pain relief, with mean pain scores
      decreasing from 4.6 to 1.8 points (P <.05). Mean active elevation improved from
      41 degrees preoperatively to 88 degrees postoperatively (P <.05), and mean
      external rotation from 22 degrees to 38 degrees (P =.045). In 11 shoulders the
      greater tuberosity resorbed or was nonunited. Two of the 25 shoulders required
      another operation after the arthroplasty: one for periprosthetic humeral fracture
      and one for instability. Twenty shoulders were much better or better, and 5 were
      the same or worse. On the basis of a modified Neer result rating system, there
      was 1 excellent result, 11 satisfactory results, and 13 unsatisfactory results.
      Patients who have significant functional impairment from a nonunion of the
      humeral surgical neck with failed internal fixation, severe osteoporosis,
      cavitation of the humeral head, or secondary osteoarthritis may benefit from
      shoulder arthroplasty. Although function is not completely restored, pain relief
      and high levels of subjective satisfaction can be achieved.

PMID- 11988722
TI  - Shoulder arthroplasty for proximal humeral malunions: long-term results.
AB  - Between 1976 and 1997, 50 shoulders with proximal humeral malunions in 50
      patients were treated with hemiarthroplasty or total shoulder arthroplasty and
      followed up for a mean of 9 years (range, 2-21 years) or until the time of
      revision surgery. Of these, 13 had a 4-part malunion, 24 had a 3-part greater
      tuberosity malunion, 6 had a 2-part greater tuberosity malunion, and 7 had a 2
      part head segment malunion. Articular incongruity resulted from an articular
      surface step-off in 5 shoulders, from osteonecrosis in 19, and from secondary
      degenerative arthritis in 26. Shoulder arthroplasty resulted in significant pain
      relief (P <.005). At most recent follow-up, shoulder pain was more intense in
      patients who had initial operative treatment of their fracture, in those with
      osteonecrosis, and in those who had arthroplasty less than 2 years after their
      fracture. Active elevation improved from 65 degrees to 102 degrees on average,
      and external rotation improved from 12 degrees to 35 degrees on average. There
      was significantly less postoperative motion in those who had initial operative
      treatment of their fracture or who underwent tuberosity osteotomy. Of the 24
      shoulders undergoing tuberosity osteotomy, 14 healed in good position, 4 had a
      nonunion develop, 3 had some degree of malunion develop, and in 3 the tuberosity
      resorbed. On the basis of the Neer result rating, 12 shoulders had an excellent
      result, 13a satisfactory result, and 25 an unsatisfactory result. Unsatisfactory
      results occurred in 8 who underwent reoperation with component revision or
      removal and because of lack of postoperative motion in 14, moderate pain in 2,
      and patient dissatisfaction in 1. All shoulders with tuberosity nonunion or
      resorption had an unsatisfactory result.

PMID- 11988723
TI  - Functional outcome after shoulder arthroplasty for primary osteoarthritis: a
      multicenter study.
AB  - Shoulder arthroplasty outcomes have been reported in many case series. Typically,
      these series have followed either a single prosthesis used to treat a variety of
      arthritic disorders of the shoulder or experience in a single institution. In
      contrast, this report of a prospective study summarizes the experience of several
      surgeons with a single prosthetic design for treatment of primary osteoarthritis
      of the shoulder. A prospective, multicenter clinical outcome study evaluated 176
      shoulders in 160 patients with primary osteoarthritis. This study evaluated a
      single prosthetic design (Global Shoulder) used by 19 contributing surgeons.
      Enrollment included 133 total shoulder replacements and 43 humeral head
      replacements (hemiarthroplasty) in 98 men and 62 women. Neither age nor sex
      affected whether hemiarthroplasty or total shoulder arthroplasty was performed.
      Patients with full-thickness cuff tears preferentially had hemiarthroplasty. The
      decision to perform total shoulder arthroplasty or hemiarthroplasty was based on
      the surgeon's preference. There were significant improvements (P <.001) in all
      evaluated and self-assessed outcome parameters from the preoperative baseline for
      both total shoulder arthroplasty and hemiarthroplasty. The results confirm that
      prosthetic arthroplasty leads to dramatic improvement in pain, function, and
      patient satisfaction. Intraoperative complications occurred in 5.4% of cases, and
      postoperative complications occurred in 7.8%. The most common intraoperative
      complications were intraoperative fractures, occurring in 9 cases. The most
      common postoperative complications were glenoid component loosening and humeral
      head subluxation. Almost all cases of humeral head instability were associated
      with rotator cuff tears or glenoid component loosening (or both). Seven shoulders
      underwent 9 additional surgeries during the 5-year study period. Thirteen
      shoulders in 11 patients were lost as a result of death unrelated to the
      procedure; 2 shoulders in 1 patient were lost within 3 days/3 months after the
      bilateral replacements as a result of death from pulmonary embolism. Nine percent
      of the shoulders (16/176) had full-thickness rotator cuff tears. Eight of the 16
      shoulders with full-thickness supraspinatus cuff tears had hemiarthroplasty. All
      of these tears were isolated to the supraspinatus tendon, and all were
      repairable. There were no differences in postoperative pain, function, American
      Shoulder and Elbow Surgeons scores, or range of motion. There were no differences
      between total shoulder arthroplasty and hemiarthroplasty in those patients with a
      reparable rotator cuff tear. Total shoulder arthroplasty and hemiarthroplasty for
      treatment of primary osteoarthritis result in good or excellent pain relief,
      improvement in function, and patient satisfaction in 95% of cases. Avoiding
      intraoperative humeral shaft fractures through use of an uncemented, canal
      filling prosthetic stem requires careful attention to reaming and component
      sizing. Postoperative humeral head subluxation is often associated with other
      factors including rotator cuff tears or glenoid component loosening.

PMID- 11988724
TI  - Tuberoplasty: creation of an acromiohumeral articulation-a treatment option for
      massive, irreparable rotator cuff tears.
AB  - This article reports the results of treatment for irreparable tears of the
      rotator cuff with a new procedure that we have termed a tuberoplasty. The
      tuberoplasty procedure involves removal of exostoses on the humerus followed by
      reshaping of the greater tuberosity to create a smooth, congruent acromiohumeral
      articulation. The coracoacromial ligament is preserved, and an acromioplasty is
      not performed. Twenty patients underwent this procedure with a minimum 27-month
      follow-up. All patients had significant disabling pain and weakness
      preoperatively. On the basis of the modified UCLA rating scale, the overall score
      increased from 9.3 to 27.7, with 12 excellent results, 6 good results, and 1 fair
      result (95% satisfactory). Pain relief was most dramatic, with 13 patients (68%)
      completely pain-free. All patients were able to perform activities of daily
      living, and 9 of 11 who were employed preoperatively returned to work. All
      patients had residual weakness in external rotation. There were no poor results
      and no complications.

PMID- 11988725
TI  - The results of functional (Sarmiento) bracing of humeral shaft fractures.
AB  - At the Department of Orthopaedics of the Kantonsspital Fribourg, 67 humeral shaft
      fractures were treated by Sarmiento bracing in a 15-year period. There were 54
      isolated fractures and 13 fractures sustained as a component of polytrauma. Fifty
      eight cases (87%) had healed clinically at a mean of 10 weeks; 9 cases failed to
      heal, so further treatment was carried out operatively. Of the conservatively
      managed fractures, 95% (55 cases) healed with an excellent or good result. Three
      patients noted a slight limitation of active range of motion, but all 58 patients
      returned to full duty at their jobs. Among 9 patients with delayed or nonunion
      leading to operative intervention, there were 6 cases with transverse fractures.
      Major reasons for failed conservative management were an incorrect indication, a
      significant axial deformity, or a hyperextended position of the fracture
      fragments. In our experience, active repositioning of humeral shaft fractures is
      not effective in avoiding a delay in fracture healing. The decision to use
      functional bracing in polytrauma patients should depend on the time of expected
      bedridden immobilization, on the presence of additional fractures of the
      ipsilateral upper extremity, and on the patient's need for crutches. The
      conservative treatment of humeral shaft fractures with the Sarmiento brace
      remains the treatment of choice, in spite of newer intramedullary operations that
      are allegedly minimally invasive and technically less complicated.

PMID- 11988726
TI  - Relationship between throwing mechanics and elbow valgus in professional baseball
      pitchers.
AB  - Valgus elbow stress leads to medial tension and lateral compression injuries in
      baseball pitchers of all ages. This study was undertaken to investigate the
      relationship between elbow stress in professional baseball pitchers and the
      kinematic parameters of pitching mechanics. This was done in an attempt to
      understand valgus extension overload better and in an effort to improve
      preventive and rehabilitative protocols. High-speed video data were collected on
      40 professional pitchers in game situations during the 1998 and 1999 Cactus
      League season in Arizona, as part of Major League Baseball Spring Training. A
      multiple linear regression analysis was used to relate elbow valgus to kinematic
      parameters of pitching mechanics. The resulting analysis produced an adjusted
      multiple R2 value of 0.974, indicating that nearly 100% of the variance in valgus
      stress on the elbow was explained by the parameters in the regression equation.
      This ability to explain over 97% of the variance in valgus stress is significant.
      The parameters of pitching mechanics related to elbow valgus may be assessed and
      optimized, if necessary, in order to decrease the magnitude of elbow stress in
      pitching.

PMID- 11988727
TI  - Radiographic analysis of lateral epicondylitis.
AB  - Lateral epicondylitis is one of the most commonly diagnosed elbow disorders, but
      the role of radiographs in clinical evaluation is unclear. The purpose of this
      study was to review a consecutive series of 294 radiographs in patients diagnosed
      with lateral epicondylitis to determine whether radiographic findings had an
      impact on patient management. Standard anteroposterior, lateral, and
      radiocapitellar views for each elbow were taken at a single upper extremity
      practice. Sixteen percent had findings present, with the most common being faint
      calcification along the lateral epicondyle in 20 patients (7%). However, in only
      2 of the 294 sets of films did the radiographs alter management. Because patients
      with lateral epicondylitis are initially managed nonoperatively, obtaining
      radiographs as an initial step in their evaluation is not necessary.

PMID- 11988728
TI  - Radiohumeral stability to forced translation: an experimental analysis of the
      bony constraint.
AB  - Radiohumeral stability to forced translation was experimentally analyzed in 8
      osteocartilaginous joint preparations. The joints were dislocated in 8
      centrifugal directions at 12 different combinations of joint flexion and rotation
      while a constant joint compression force of 23 N was applied. Stability was
      measured as the maximum resistance to translation. On average, the specimens
      could resist a transverse force of 16.4 N (range, 13.0-19.1 N). Stability was
      greater in some directions than in others. Rotating the joint changed the
      direction at which stability was greatest, whereas joint flexion did not. In
      supination, the greatest stability was observed for anteromedial dislocations, in
      neutral rotation for posteromedial dislocations, and in pronation for
      posterolateral dislocations. The findings from this study indicate systematic
      variations in wall height around the radial head concavity as well as individual
      variations in joint constraint. This may have implications for the treatment of
      conditions involving radiohumeral joint dislocation.

PMID- 11988729
TI  - Experimental fascial autografting for the supraspinatus tendon defect: remodeling
      process of the grafted fascia and the insertion into bone.
AB  - To elucidate the postoperative histologic changes of fascial autografting,
      tendinous defects (1.5 x 1.5 cm) were created close to the supraspinatus
      insertion and were covered by fascial autografts in 21 rabbits. Shoulders
      harvested on the fourth day and 1, 2, 3, 4, 6, and 8 weeks after surgery were
      examined histologically and immunohistochemically. At the fascia-bone junction,
      chondrocytes started to appear at 2 weeks after surgery and increased rapidly
      thereafter. Although a tidemark was not seen, remodeling of direct insertion with
      fibrocartilage was almost complete by 8 weeks. The distribution of collagen types
      II and III represented a pattern similar to that of a normal supraspinatus tendon
      insertion. In the grafted fascia, the cellular density showed a marked increase
      over time (r2 = 0.74, P <.0001). Our study revealed that both the tendinous
      tissue and its insertion were reformed after this procedure. Fascial autografting
      might be useful for repairing a supraspinatus tendon defect.

PMID- 11988730
TI  - The mineralization patterns at the subchondral bone plate of the glenoid cavity
      in healthy shoulders.
AB  - The distribution of mineralization of the subchondral bone plate (DMSB) is used
      as a parameter for the individual stress distribution of joints. In this study
      the DMSB of the glenoid from healthy glenohumeral joints was analyzed. In a
      standardized manner, 44 macroscopically normal shoulder specimens (28 individuals
      aged 18 to 96 years) were selected and DMSB of the glenoid was evaluated by
      computed tomography osteoabsorptiometry. The mineralization patterns were
      described, and the 2 most frequent maxima of density were localized and
      statistically assessed to analyze any influence of age, side, or shape of the
      glenoid on DMSB. An anterior-superior maximum was found in 100% and a posterior
      maximum in 82%. Three different patterns of DMSB were distinguished in relation
      to the constant anterior-superior maximum: 68% were not combined with a further
      central or anterior-inferior maximum (type A), whereas a central maximum
      coexisted in 18% (type B) and an anterior-inferior maximum in 14% (type C). The
      localization of the anterior-superior and posterior maxima was independent of age
      or side of the glenoid, indicating a constant long-term stress distribution in
      healthy glenohumeral joints. The typical localization of the density maxima
      showed that stress distribution is usually peripherical (82%) and often
      bicentric. Functional aspects related to internal rotation of the arm support a
      more constant anterior than posterior stress on the glenoid surface.

PMID- 11988731
TI  - A case of post-traumatic osteolysis of the distal clavicle: histologic lesion of
      the acromion.

PMID- 11988732
TI  - Total shoulder arthroplasty in pigmented villonodular synovitis: a case report.

PMID- 11988733
TI  - Observation on retrieved Hylamer glenoids in shoulder arthroplasty: problems
      associated with sterilization by gamma irradiation in air.
AB  - Hylamer is an ultra-high molecular weight polyethylene that was used in the
      glenoid prosthesis of the Global Shoulder. It was developed from a joint venture
      with DePuy Orthopaedics, Inc, and E.I. DuPont Company. In presterilization
      evaluations it was noted to have improved mechanical strength with superior creep
      and wear resistance. However, after sterilization was performed with gamma
      irradiation in an air environment from 1990 to 1993, the Hylamer glenoids were
      affected by oxidation, which altered the mechanical properties, and they became
      brittle and eroded. From 1993 to 1995 Hylamer glenoids were sterilized by gamma
      irradiation in a nitrogen environment. From 1995 to 1998 sterilization was by gas
      plasma processes, which do not create the oxidation problem. Since 1998 the
      glenoid prosthesis of the Global Shoulder has been made exclusively of Enduron
      and is gas sterilized. The primary purpose of this article is to provide
      orthopaedic surgeons the best information available about Hylamer glenoids. We
      make suggestions concerning the diagnosis and treatment of the patients who had a
      Hylamer glenoid inserted between 1990 and 1993.

PMID- 11988735
TI  - Open surgical release for frozen shoulder.

PMID- 11988737
TI  - Ras signalling on the endoplasmic reticulum and the Golgi.
AB  - Current models evoke the plasma membrane (PM) as the exclusive platform from
      which Ras regulates signalling. We developed a fluorescent probe that reports
      where and when Ras is activated in living cells. We show that oncogenic H-Ras and
      N-Ras engage Raf-1 on the Golgi and that endogenous Ras and unpalmitoylated H-Ras
      are activated in response to mitogens on the Golgi and endoplasmic reticulum
      (ER), respectively. We also demonstrate that H-Ras that is restricted to the ER
      can activate the Erk pathway and transform fibroblasts, and that Ras localized on
      different membrane compartments differentially engages various signalling
      pathways. Thus, Ras signalling is not limited to the PM, but also proceeds on the
      endomembrane.

PMID- 11988738
TI  - E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting
      APC(Cdh1).
AB  - Emi1 promotes mitotic entry in Xenopus laevis embryos by inhibiting the
      APC(Cdc20) ubiquitination complex to allow accumulation of cyclin B. We show here
      that human Emi1 (hEmi1) functions to promote cyclin A accumulation and S phase
      entry in somatic cells by inhibiting the APC(Cdh1) complex. At the G1-S
      transition, hEmi1 is transcriptionally induced by the E2F transcription factor,
      much like cyclin A. hEmi1 overexpression accelerates S phase entry and can
      override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105
      retinoblastoma protein (pRb). Depleting cells of hEmi1 through RNA interference
      prevents accumulation of cyclin A and inhibits S phase entry. These data suggest
      that E2F can activate both transcription of cyclin A and the hEmi1-dependent
      stabilization of APC(Cdh1) targets, such as cyclin A, to promote S phase entry.

PMID- 11988739
TI  - A new nuclear component of the Wnt signalling pathway.
AB  - The Wnt signalling pathway is pivotal in normal and malignant development. A key
      effector is Armadillo (Arm)/beta-catenin, which functions with TCF to transcribe
      Wnt target-genes. Here, we report the discovery of pygopus (pygo), whose mutant
      phenotypes specifically mimic loss-of-Wingless (Wg) signalling. pygo is required
      for dTCF-mediated transcription, but not for Wg-induced stabilization of Arm.
      Pygo is a nuclear protein that is found in a complex with Arm in vivo. Humans
      possess two Pygo proteins, both of which are required for TCF-mediated
      transcription in colorectal cancer cells. The presence of a PHD domain implicates
      Pygo proteins in a chromatin-related function, and we propose that they mediate
      chromatin access to TCF or Arm/beta-catenin.

PMID- 11988740
TI  - Dysfunction of store-operated calcium channel in muscle cells lacking mg29.
AB  - The store-operated calcium channel (SOC) located in the plasma membrane (PM)
      mediates capacitative entry of extracellular calcium after depletion of
      intracellular calcium stores in the endoplasmic or sarcoplasmic reticulum
      (ER/SR). An intimate interaction between the PM and the ER/SR is essential for
      the operation of this calcium signalling pathway. Mitsugumin 29 (MG29) is a
      synaptophysin-family-related protein located in the junction between the PM and
      SR of skeletal muscle. Here, we identify SOC in skeletal muscle and characterise
      its regulation by MG29 and the ryanodine receptor (RyR) located in the SR.
      Targeted deletion of mg29 alters the junctional membrane structure, causes severe
      dysfunction of SOC and SR calcium homeostasis and increases the susceptibility of
      muscle to fatigue stimulation. Severe dysfunction of SOC is also identified in
      muscle cells lacking both type 1 and type 3 RyRs, indicating that SOC activation
      requires an intact interaction between the PM and the SR, and is linked to
      conformational changes of RyRs. Whereas defective SOC seems to be inconsequential
      to short-term excitation-contraction coupling, the slow cumulative calcium entry
      through SOC is crucial for long-term calcium homeostasis, such that reduced SOC
      activity exaggerates muscle fatigue under conditions of intensive exercise.

PMID- 11988741
TI  - Maintenance of replication forks and the S-phase checkpoint by Cdc18p and Orp1p.
AB  - S-phase and DNA damage checkpoint controls block the onset of mitosis when DNA is
      damaged or DNA replication is incomplete. It has been proposed that damaged or
      incompletely replicated DNA generates structures that are sensed by the
      checkpoint control pathway, although little is known about the structures and
      mechanisms involved. Here, we show that the DNA replication initiation proteins
      Orp1p and Cdc18p are required to induce and maintain the S-phase checkpoint in
      Schizosaccharomyces pombe. The presence of DNA replication structures correlates
      with activation of the Cds1p checkpoint protein kinase and the S-phase checkpoint
      pathway. By contrast, induction of the DNA damage pathway is not dependent on
      Orp1p or Cdc18p. We propose that the presence of unresolved replication forks,
      together with Orp1p and Cdc18p, are necessary to activate the Cds1p-dependent S
      phase checkpoint.

PMID- 11988742
TI  - Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor
      endocytosis.
AB  - Ubiquitin functions as a signal for sorting cargo at multiple steps of the
      endocytic pathway and controls the activity of trans-acting components of the
      endocytic machinery (reviewed in refs 1, and 2). By contrast to proteasome
      degradation, which generally requires a polyubiquitin chain that is at least four
      subunits long, internalization and sorting of endocytic cargo at the late
      endosome are mediated by mono-ubiquitination. Here, we demonstrate that ubiquitin
      interacting motifs (UIMs) found in epsins and Vps27p (ref. 9) from Saccharomyces
      cerevisiae are required for ubiquitin binding and protein transport. Epsin UIMs
      are important for the internalization of receptors into vesicles at the plasma
      membrane. Vps27p UIMs are necessary to sort biosynthetic and endocytic cargo into
      vesicles that bud into the lumen of a late endosomal compartment, the
      multivesicular body. We propose that mono-ubiquitin regulates internalization and
      endosomal sorting by interacting with modular ubiquitin-binding domains in core
      components of the protein transport machinery. UIM domains are found in a broad
      spectrum of proteins, consistent with the idea that mono-ubiquitin can function
      as a regulatory signal to control diverse biological activities.

PMID- 11988745
TI  - An integrative future.

PMID- 11988743
TI  - Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early
      endosomes.
AB  - After endocytosis, some membrane proteins recycle from early endosomes to the
      plasma membrane whereas others are transported to late endosomes and lysosomes
      for degradation. Conjugation with the small polypeptide ubiquitin is a signal for
      lysosomal sorting. Here we show that the hepatocyte growth factor-regulated
      tyrosine kinase substrate, Hrs, is involved in the endosomal sorting of
      ubiquitinated membrane proteins. Hrs contains a clathrin-binding domain, and by
      electron microscopy we show that Hrs localizes to flat clathrin lattices on early
      endosomes. We demonstrate that Hrs binds directly to ubiquitin by way of a
      ubiquitin-interacting motif (UIM), and that ubiquitinated proteins localize
      specifically to Hrs- and clathrin-containing microdomains. Whereas endocytosed
      transferrin receptors fail to colocalize with Hrs and rapidly recycle to the cell
      surface, transferrin receptors that are fused to ubiquitin interact with Hrs,
      localize to Hrs- and clathrin-containing microdomains and are sorted to the
      degradative pathway. Overexpression of Hrs strongly and specifically inhibits
      recycling of ubiquitinated transferrin receptors by a mechanism that requires a
      functional UIM. We conclude that Hrs sorts ubiquitinated membrane proteins into
      clathrin-coated microdomains of early endosomes, thereby preventing their
      recycling to the cell surface.

PMID- 11988746
TI  - Amyloid-lowering isocoumarins are not direct inhibitors of gamma-secretase.

PMID- 11988747
TI  - Chronic granulomatous disease mutations and the PX domain.

PMID- 11988749
TI  - Taking a bite: proteasomal protein processing.
AB  - The proteasome is a hollow cylindrical protease that contains active sites
      concealed within its central cavity. Proteasomes usually completely degrade
      substrates into small peptides, but in a few cases, degradation can yield
      biologically active protein fragments. Examples of this are the transcription
      factors NF-kappa B, Spt23p and Mga2p, which are generated from precursors by
      proteasomal processing. How distinct protein domains are spared from degradation
      remains a matter of debate. Here, we discuss several models and suggest a novel
      mechanism for proteasomal processing.

PMID- 11988750
TI  - Cell polarity: Oskar seeks PARtner for a stable relationship.

PMID- 11988751
TI  - Conspiracy to disarm APC in interphase.

PMID- 11988752
TI  - Ubiquitin chained and crosslinked.

PMID- 11988753
TI  - An encore for kiss and run?

PMID- 11988754
TI  - Getting legless with a Pygopus.

PMID- 11988757
TI  - The origins of protein phosphorylation.
AB  - The reversible phosphorylation of proteins is central to the regulation of most
      aspects of cell function but, even after the first protein kinase was identified,
      the general significance of this discovery was slow to be appreciated. Here I
      review the discovery of protein phosphorylation and give a personal view of the
      key findings that have helped to shape the field as we know it today.

PMID- 11988758
TI  - AP-1 as a regulator of cell life and death.
AB  - The transcription factor AP-1 (activator protein-1) is involved in cellular
      proliferation, transformation and death. Using mice and cells lacking AP-1
      components, the target-genes and molecular mechanisms mediating these processes
      were recently identified. Interestingly, the growth-promoting activity of c-Jun
      is mediated by repression of tumour suppressors, as well as upregulation of
      positive cell cycle regulators. Mostly, c-Jun is a positive regulator of cell
      proliferation, whereas JunB has the converse effect. The intricate relationships
      between the different Jun proteins, their activities and the mechanisms that
      mediate them will be discussed.

PMID- 11988759
TI  - Plant transposable elements: where genetics meets genomics.
AB  - Transposable elements are the single largest component of the genetic material of
      most eukaryotes. The recent availability of large quantities of genomic sequence
      has led to a shift from the genetic characterization of single elements to genome
      wide analysis of enormous transposable-element populations. Nowhere is this shift
      more evident than in plants, in which transposable elements were first discovered
      and where they are still actively reshaping genomes.

PMID- 11988760
TI  - Life is a journey: a genetic look at neocortical development.
AB  - Although the basic principles of neocortical development have been known for
      quite some time, it is only recently that our understanding of the molecular
      mechanisms that are involved has improved. Such understanding has been
      facilitated by genetic approaches that have identified key proteins involved in
      neocortical development, which have been placed into signalling pathways by
      molecular and cell-biological studies. The challenge of current research is to
      understand the manner in which these various signalling pathways are
      interconnected to gain a more comprehensive picture of the molecular intricacies
      that govern neocortical development.

PMID- 11988761
TI  - The art and design of genetic screens: caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans was chosen as a model genetic organism
      because its attributes, chiefly its hermaphroditic lifestyle and rapid generation
      time, make it suitable for the isolation and characterization of genetic mutants.
      The most important challenge for the geneticist is to design a genetic screen
      that will identify mutations that specifically disrupt the biological process of
      interest. Since 1974, when Sydney Brenner published his pioneering genetic
      screen, researchers have developed increasingly powerful methods for identifying
      genes and genetic pathways in C. elegans.

PMID- 11988762
TI  - Alu repeats and human genomic diversity.
AB  - During the past 65 million years, Alu elements have propagated to more than one
      million copies in primate genomes, which has resulted in the generation of a
      series of Alu subfamilies of different ages. Alu elements affect the genome in
      several ways, causing insertion mutations, recombination between elements, gene
      conversion and alterations in gene expression. Alu-insertion polymorphisms are a
      boon for the study of human population genetics and primate comparative genomics
      because they are neutral genetic markers of identical descent with known
      ancestral states.

PMID- 11988763
TI  - Genealogical trees, coalescent theory and the analysis of genetic polymorphisms.
AB  - Improvements in genotyping technologies have led to the increased use of genetic
      polymorphism for inference about population phenomena, such as migration and
      selection. Such inference presents a challenge, because polymorphism data reflect
      a unique, complex, non-repeatable evolutionary history. Traditional analysis
      methods do not take this into account. A stochastic process known as the
      'coalescent' presents a coherent statistical framework for analysis of genetic
      polymorphisms.

PMID- 11988764
TI  - Candidate-gene approaches for studying complex genetic traits: practical
      considerations.
AB  - Association studies with candidate genes have been widely used for the study of
      complex diseases. However, this approach has been criticized because of non
      replication of results and limits on its ability to include all possible
      causative genes and polymorphisms. These challenges have led to pessimism about
      the candidate-gene approach and about the genetic analysis of complex diseases in
      general. We believe that these criticisms can be usefully countered with an
      appeal to the principles of epidemiological investigation.

PMID- 11988765
TI  - Timeline: Neurospora: a model of model microbes.
AB  - In the 1940s, studies with Neurospora pioneered the use of microorganisms in
      genetic analysis and provided the foundations for biochemical genetics and
      molecular biology. What has happened since this orange mould was used to show
      that genes control metabolic reactions? How did it come to be the fungal
      counterpart of Drosophila? We describe its continued use during the heyday of
      research with Escherichia coli and yeast, and its emergence as a biological model
      for higher fungi.

PMID- 11988766
TI  - The Mre11 complex: at the crossroads of dna repair and checkpoint signalling.
AB  - The Mre11 complex is a multisubunit nuclease that is composed of Mre11, Rad50 and
      Nbs1/Xrs2. Mutations in the genes that encode components of this complex result
      in DNA- damage sensitivity, genomic instability, telomere shortening and aberrant
      meiosis. The molecular defect that underlies these phenotypes has long been
      thought to be related to a DNA repair deficiency. However, recent studies have
      uncovered functions for the Mre11 complex in checkpoint signalling and DNA
      replication.

PMID- 11988767
TI  - The subcellular destinations of APC proteins.
AB  - Adenomatous polyposis coli (APC) is an important tumour suppressor in the human
      colon, and is conserved in various organisms. Its best understood function is the
      destabilization of beta-catenin, a key effector of the Wnt signalling pathway.
      APC proteins are highly motile, and shuttle between several subcellular
      destinations. These destinations have prompted the discovery of new functions for
      the APC proteins, and this multitasking of APC might explain why its loss often
      leads to cancer.

PMID- 11988768
TI  - Integration of calcium and Ras signalling.
AB  - Calcium is a universal intracellular signal that is responsible for controlling a
      plethora of cellular processes. Understanding how such a simple ion can regulate
      so many diverse cellular processes is a key goal of calcium- and cell-biologists.
      One molecule that is sensitive to changes in intracellular calcium levels is Ras.
      This small GTPase operates as a binary molecular switch, and regulates cell
      proliferation and differentiation. Here, we focus on examining the link between
      calcium and Ras signalling and, in particular, we speculate as to how the
      complexity of calcium signalling could regulate Ras activity.

PMID- 11988769
TI  - Myofibroblasts and mechano-regulation of connective tissue remodelling.
AB  - During the past 20 years, it has become generally accepted that the modulation of
      fibroblastic cells towards the myofibroblastic phenotype, with acquisition of
      specialized contractile features, is essential for connective-tissue remodelling
      during normal and pathological wound healing. Yet the myofibroblast still remains
      one of the most enigmatic of cells, not least owing to its transient appearance
      in association with connective-tissue injury and to the difficulties in
      establishing its role in the production of tissue contracture. It is clear that
      our understanding of the myofibroblast   its origins, functions and molecular
      regulation   will have a profound influence on the future effectiveness not only
      of tissue engineering but also of regenerative medicine generally.

PMID- 11988770
TI  - The 3' 5' exonucleases.
AB  - Over the past few years, several new 3' 5' exonucleases have been identified. In
      vitro studies of these enzymes have uncovered much about their potential
      functions in vivo, and certain organisms with a defect in 3' 5' exonucleases have
      an increased susceptibility to cancer, especially under conditions of stress.
      Here, we look at not only the newly discovered enzymes, but also at the roles of
      other 3' 5' exonucleases in the quality control of DNA synthesis, where they act
      as proofreading exonucleases for DNA polymerases during DNA replication, repair
      and recombination.

PMID- 11988771
TI  - Timeline: the march of structural biology.
AB  - One hundred years ago, we knew very little about biological macromolecules and
      had no tools available to study their structure. Structural biology is now a
      mature science. New structures are being solved at an ever-increasing rate and
      there are important new initiatives to determine all the protein folds that are
      used by biological systems (structural genomics). This article traces some of the
      key developments in the field.

PMID- 11988772
TI  - Opinion: peroxisomal-protein import: is it really that complex?
AB  - Peroxisomal enzymes are synthesized in the cytoplasm and imported post
      translationally across the peroxisome membrane. Unlike other organelles with a
      sealed membrane, peroxisomes can import folded enzymes, and they seem to lack
      intraperoxisomal chaperones. Here, we propose a mechanistic model for the early
      steps in peroxisomal-matrix-enzyme import, which might help to explain the
      unusual features of this process.

PMID- 11988774
TI  - Intermanual coordination: from behavioural principles to neural-network
      interactions.
AB  - Locomotion in vertebrates and invertebrates has a long history in research as the
      most prominent example of interlimb coordination. However, the evolution towards
      upright stance and gait has paved the way for a bewildering variety of functions
      in which the upper limbs interact with each other in a context-specific manner.
      The neural basis of these bimanual interactions has been investigated in recent
      years on different scales, ranging from the single-cell level to the analysis of
      neuronal assemblies. Although the prevailing viewpoint has been to assign
      bimanual coordination to a single brain locus, more recent evidence points to a
      distributed network that governs the processes of neural synchronization and
      desynchronization that underlie the rich variety of coordinated functions. The
      distributed nature of this network accounts for disruptions of interlimb
      coordination across various movement disorders.

PMID- 11988773
TI  - The hypocretins: setting the arousal threshold.
AB  - Over a short period in the late 1990s, three groups converged on the discovery of
      a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates
      arousal states, influences feeding and is implicated in the sleep disorder
      narcolepsy. Subsequent studies have illuminated many aspects of the circuitry of
      the hypocretin (also called orexin) system, which also influences hormone
      secretion and autonomic homeostasis, and have led to the hypothesis that most
      human narcolepsies result from an autoimmune attack against the hypocretin
      producing neurons. The biochemical, physiological and anatomical components that
      regulate the switch between waking and sleeping are becoming clear. The rapidity
      with which the hypocretin story has emerged is a testament to both the conceptual
      and the technical evolution of genomic science in the past two decades.

PMID- 11988775
TI  - Emerging rules for the distributions of active dendritic conductances.
AB  - A key goal in neuroscience is to explain how the operations of a neuron emerge
      from sets of active channels with specific dendritic distributions. If general
      principles can be identified for these distributions, dendritic channels should
      reflect the computational role of a given cell type within its functional neural
      circuit. Here, we discuss insights from experimental and computational data on
      the distribution of voltage-gated channels in dendrites, and attempt to derive
      rules for how their interactions implement different dendritic functions. We
      propose that this type of analysis will be important for understanding
      behavioural processes in terms of single-neuron properties, and that it
      constitutes a step towards a 'functional proteomics' of nerve cells, which will
      be essential for defining neuronal phenotypes.

PMID- 11988776
TI  - Childhood absence epilepsy: genes, channels, neurons and networks.
AB  - Childhood absence epilepsy is an idiopathic, generalized non-convulsive epilepsy
      with a multifactorial genetic aetiology. Molecular-genetic analyses of affected
      human families and experimental models, together with neurobiological
      investigations, have led to important breakthroughs in the identification of
      candidate genes and loci, and potential pathophysiological mechanisms for this
      type of epilepsy. Here, we review these results, and compare the human and
      experimental phenotypes that have been investigated. Continuing efforts and
      comparisons of this type will help us to elucidate the multigenetic traits and
      pathophysiology of this form of generalized epilepsy.

PMID- 11988777
TI  - The GDNF family: signalling, biological functions and therapeutic value.
AB  - Members of the nerve growth factor (NGF) and glial cell line-derived neurotrophic
      factor (GDNF) families   comprising neurotrophins and GDNF-family ligands (GFLs),
      respectively   are crucial for the development and maintenance of distinct sets
      of central and peripheral neurons. Knockout studies in the mouse have revealed
      that members of these two families might collaborate or act sequentially in a
      given neuron. Although neurotrophins and GFLs activate common intracellular
      signalling pathways through their receptor tyrosine kinases, several clear
      differences exist between these families of trophic factors.

PMID- 11988778
TI  - Timeline: exorcizing the animal spirits: Jan Swammerdam on nerve function.
AB  - For more than 1,500 years, nerves were thought to function through the action of
      'animal spirits'. In the seventeenth century, Rene Descartes conceived of these
      'spirits' as liquids or gases, and used the idea to explain reflex action. But he
      was rapidly proven wrong by a young Dutchman, Jan Swammerdam. Swammerdam's
      elegant experiments pioneered the frog nerve muscle preparation and laid the
      foundation of our modern understanding of nerve function.

PMID- 11988779
TI  - Opinion: neural stem cell therapy for neurological diseases: dreams and reality.
AB  - There is a pressing need for treatments for neurodegenerative diseases. Hopes
      have been raised by the prospect of neural stem cell therapy; however, despite
      intense research activities and media attention, stem cell therapy for
      neurological disorders is still a distant goal. Effective strategies must be
      developed to isolate, enrich and propagate homogeneous populations of neural stem
      cells, and to identify the molecules and mechanisms that are required for their
      proper integration into the injured brain. This article examines these
      requirements, discusses the results obtained so far, and considers the steps that
      need to be taken to provide instruction to donor cells and to elucidate the
      neurogenic potential of the adult central nervous system environment.

PMID- 11988789
TI  - Endoscopic surgery in Senegal. Benefits, costs and limits.
AB  - BACKGROUND: Evaluating the introduction of endoscopic surgery in Senegal may be
      useful for assessing the role of this technology in developing countries.
      METHODS: The endoscopic surgery performed at the Hospital Principal and the
      Hospital Le Dantec, Dakar, from January 1995 to December 2000 was evaluated
      retrospectively. Operative time, postoperative stay, patients, and hospital costs
      were compared in samples of 100 patients treated endoscopically and 80 patients
      treated with open techniques. RESULTS: Altogether, 826 endoscopic procedures were
      performed (11.6% of elective surgical activity). Of these, thoracoscopic (34%)
      and laparoscopic (14%) vagotomy, cholecystectomy (21%), fundoplication (12%), and
      diagnostic laparoscopy (11%) were selected for comparisons. Operative time proved
      to be reduced by endoscopic surgery except for laparoscopic fundoplication (+40
      min). After endoscopic surgery, postoperative hospitalization was 3.7 days
      shorter, and patient fees were consequently reduced. In 6 years, 87% of the
      hospital investment (36,000 Euro) was recovered. CONCLUSIONS: Developing
      countries can benefit from endoscopic surgery. First-world countries might supply
      staff training.

PMID- 11988790
TI  - Laparoscopic transgastric endoscopic retrograde cholangiopancreatography for
      benign common bile duct stricture after Roux-en-Y gastric bypass.
AB  - Access to the gastric remnant and duodenum is lost after laparoscopic Roux-en-Y
      gastric bypass for morbid obesity. Traditionally, a percutaneous transhepatic
      access to the common bile duct has been used to manage choledocholithiasis and
      duct strictures. We present a novel method of laparoscopic transgastric
      endoscopic retrograde cholangiopancreatography for managing a benign biliary
      stricture after a Roux-en-Y gastric bypass.

PMID- 11988791
TI  - Thoracoscopic treatment for spontaneous hemopneumothorax.
AB  - Spontaneous hemopneumothorax is a rare clinical entity sometimes requiring an
      operation in the early stage. Two patients who underwent successful video
      assisted thoracic surgery (VATS) for spontaneous hemopneumothorax are presented.
      In both cases, the bleeding point was clearly identified, and hemostasis was
      easily obtained by clipping the point and placing three access ports in the usual
      fashion. Furthermore, the evacuation of clotted blood and resection of bulla were
      performed with no difficulties. The postoperative courses were smooth, and no
      complications occurred, although the preoperative general condition in the second
      case was hemodynamically unstable. The advantages of VATS over conventional
      thoracotomy include less time required to access the pleural cavity, a better
      view, and more facilitated manipulation during surgery. Because spontaneous
      hemopneumothorax is a benign disease, VATS should be considered an initial
      treatment option in all patients with this condition, even those with active
      bleeding.

PMID- 11988792
TI  - Ectopic liver (choristoma) associated with the gallbladder encountered during
      laparoscopic cholecystectomy: a case report.
AB  - Ectopic liver has been but rarely described usually in the vicinity of liver such
      as on the gallbladder, hepatic ligaments, diaphragm, thoracic cavity, adrenal
      glands, pancreas, omentum, spleen, esophagus and umbilical cord. A simple
      classification for anomalous liver tissues found on the wall of gallbladder is 1.
      Accessory liver lobe 2. Ectopic nodule 3. Aberrant microscopic tissue. Ectopic
      nodules of liver tissue attached to the gallbladder are completely detached from
      the liver and has been described by various names such as accessory lobe, ectopic
      liver, accessory liver and heterotopic liver but the specific pathological term
      for this entity is choristoma introduced by Albert in 1904 meaning displacement.
      Several possible mechanisms may explain ectopic liver at various sites such as
      the development of an accessory lobe of the liver with atrophy or regression of
      the original connection to the main liver or migration of pars hepatica to the
      rudiment of various organs. In this paper we present a case of ectopic liver or
      choristoma attached to the gallbladder encountered during an elective
      laparoscopic cholecystectomy which was successfully removed with the gallbladder.

PMID- 11988793
TI  - Retroperineoscopic excision of a single blind ectopic ureter in childhood.
AB  - Retroperitoneoscopy is gradually gaining in importance in pediatric urology,
      especially for renal and adrenal diseases. Direct retroperitoneal pelvic access
      seems interesting in children when low urinary tract malformations are concerned.
      We report a case of a 12-year-old boy with a blind ectopic ureter managed by
      pelvic retroperitoneoscopy. We describe the surgical technique, focusing on the
      difficulty in the pediatric population. Nevertheless, retroperitoneoscopy is an
      excellent alternate way to manage such ureteral malformations.

PMID- 11988794
TI  - Pericardial drainage using the transdiaphragmatic route: refinement of the
      laparoscopic technique.
AB  - Four patients with malignant pericardial fluid requiring permanent drainage are
      reported. A three-port video-assisted thoracoscopic surgery modification of the
      pericardioperitoneal shunt procedure is described, in which the Ultracision
      Harmonic Scalpel is used. The supraumbilically introduced camera secures direct
      vision for the trocars in the left and the right hypochondrium of the patient in
      a modified lithotomy position. Grasping the diaphragm anterolateral to the hiatus
      esophagei with the manipulator, we cut through the diaphragm-pericardium complex
      with the Harmonic Scalpel. After creation of a hole with a diameter 3 to 5 cm,
      the abdomen is closed without a drain. The usage of Ultracision scalpel minimizes
      the risk of epicardium injury previously described with the use of scissors or
      electrocautery. Clips are unnecessary because the Harmonic Scalpel has a sealing
      effect. Two figures demonstrate the port placements and the facilitated cutting
      with the Harmonic Scalpel. Four patients underwent surgery using the described
      technique. All of them suffered from ultrasound-guided tapping or drainage
      resistant, lung cancer-related malignant pericardial fluid, which caused
      pericardial tamponade. All the procedures were successful. The technique is easy
      to learn and simple to perform.

PMID- 11988795
TI  - Subxiphoid approach for thoracoscopic thymectomy.
AB  - Avoiding sternotomy, cumulative experience has demonstrated the efficacy and
      safety of minimally invasive thoracoscopic thymectomy. Previous reports
      describing the transcervical, left or right thoracic approach, although
      demonstrating promising results, involve some compromise of the surgical
      exposure. We designed a new approach through the subxiphoid route to perform
      extended thymectomy using the standard thoracoscopic technique. We used this
      approach on two consecutive patients. Additional port sites were created on both
      sides of the anterior chest wall for introducing instruments. This approach
      provides an excellent view of the bilateral pleural cavities, which is essential
      for adequate mediastinal fatty tissue dissection, especially because the surgical
      plan calls for removal of all the bilateral pericardiophrenic fat pads and the
      mediastinal fat tissue between the bilateral phrenic nerves. This approach omits
      the sternotomy while making extended thymectomy possible through the bilateral
      access. All the possible thymic-bearing mediastinal fat tissues can be removed
      under direct thoracoscopic view, which may subsequently translate into better
      results.

PMID- 11988796
TI  - Major vascular injuries in laparoscopic surgery.
AB  - BACKGROUND: Major vascular injuries (MVI) still occur in laparoscopic surgery.
      METHODS: We report our institution's experience of two MVI (aortic lesions) in a
      series of 3545 laparoscopies (July 1991-December 2000). We compared this
      experience with other series reporting MVI from Medline, Embase, Current
      Contents, and Best Evidence. RESULTS: There were no deaths, but we had 23
      postoperative and eight intraoperative bleedings, including two hepatic vessel
      lesions during dissection and six vascular lesions (four minor vessels and two
      aortic) related to trocar insertion. Prevention and treatment options are also
      discussed. CONCLUSIONS: The incidence of MVI reported in the literature is 0.05%,
      but the true incidence is difficult to estimate because results are not always
      comparable and there is a possibility of underreporting. The mortality rates (8
      17%) are high. No technique or instrumentation is completely safe; therefore, a
      high level of alertness must be maintained at all times and precautions must be
      adopted to avoid major complications.

PMID- 11988797
TI  - Comparative study of three-dimensional and conventional endorectal
      ultrasonography used in rectal cancer staging.
AB  - BACKGROUND: Three-dimensional (3D) imaging offers improved knowledge of various
      anatomic structures and tumors by providing 3D images. This prospective study was
      performed to verify whether 3D endorectal ultrasonography (EUS) enhances the
      accuracy of rectal cancer staging, as compared with conventional EUS. METHODS:
      Using both 3D and conventional EUS, 33 consecutive patients with operable rectal
      cancer were preoperatively staged. A rigid 3D probe with a scanner was used for
      3D EUS, and a rigid endorectal probe with a scanner was used for conventional
      EUS. RESULTS: The accuracy of 3D EUS was 90.9% for pT2 and 84.8% for pT3, whereas
      that of conventional EUS was 84.8% and 75.8%, respectively, thereby showing no
      difference between these two methods. The lymph node metastasis was accurately
      predicted by 3D EUS in 28 patients (84.8%), whereas conventional EUS predicted
      the disorder in 22 patients (66.7%). The difference was not statistically
      significant. The average infiltration grade of the circumference on transverse 3D
      EUS scans was associated closely with advancement of the TNM stage (p <0.001
      0.006) and lymph node metastasis (p = 0.003). The presence of a cone-shaped
      surface on the deep tumor border correlated with the infiltration grade shown on
      all of the sectional displays (p <0.001-0.042) and with advancement of the TNM
      stage (p = 0.018). CONCLUSIONS: Although the findings did not show 3D EUS to have
      a significant advantage over conventional EUS for the accurate evaluation of
      rectal cancer, a numeric advantage may possibly be statistically significant in a
      further study with larger cases. Furthermore, stereoscopic visualization provided
      easier and complete understanding of both focal lesions and lymph nodes.

PMID- 11988798
TI  - The influence of new technologies on laparoscopic adrenalectomy: our personal
      experience with 91 patients.
AB  - BACKGROUND: Laparoscopic adrenalectomy has proved to be the technique of choice
      for managing benign pathologies of the adrenals and isolated adrenal metastases,
      especially those arising from lung tumor, but the procedure should not be
      performed for primitive adrenal carcinoma. The Authors wanted to test the
      advantages of the Harmonic Scalpel in laparoscopic adrenalectomy. METHODS: From
      April 1995 to April 2001, the authors investigated their series of laparoscopic
      adrenalectomies performed at the Careggi General Hospital, Division of General
      and Vascular Surgery, Florence, Italy. This study enrolled 91 patients with
      various adrenal pathologies. The transperitoneal approach was used, with the
      patient in a lateral position, as suggested by Gagner. Special care was taken to
      improve the surgical approach to the adrenals by the use of new technological
      devices such as the Harmonic Scalpel. The operative time required by the surgical
      procedure was computed by dividing the study into three periods: 1995-1997, 1998
      1999, 2000-2001. The first period was necessary to complete the learning curve.
      In the second period, a steady state in surgical time was reached. During the
      third period, the Harmonic Scalpel was introduced. The differences between the
      three periods were tested using a nonparametric analysis (Mann-Whitney U test or
      Kruskal-Wallis test) as appropriate. A two-tailed p value of 0.05 or less was
      considered statistically significant. The authors investigated the cost of the
      operation performed in each of the two groups using, respectively, the
      conventional laparoscopic device (1998-1999) and the Harmonic Scalpel (2000
      2001). The following expenses were considered: Harmonic Scalpel impulse generator
      and disposable shears, operating room cost per hour, and endoclip applier.
      RESULTS: The 91 laparoscopic adrenalectomies were performed with these
      indications: 31 incidentalomas (26 adenomas and 5 cysts), 25 cases of Conn's
      disease, 18 cases of Cushing's disease, 9 pheochromocytomas, 2 myelolipomas, 5
      metastases (from lung, kidney, and breast) and 1 primitive carcinoma diagnosed
      preoperatively. Considering the whole series (1995-2001), there was a significant
      trend of reduction in operative time (p = 0.0001). Moreover looking at the first
      period (1995-1997), in which the learning curve was completed, the mean surgical
      time was 148 min, as compared with 125 mm. For the second period (1998-1999) (p =
      0.0002). This represents a significant reduction in operative time. The authors
      noted a further reduction in the operative time when surgery was performed with
      the Harmonic Scalpel (2000-2001) (92 min; p = 0.001). The reduction in operative
      time attributable to the Harmonic Scalpel was confirmed also by a multivariate
      analysis of covariance general linear models procedure (GLM), which accounts for
      several confounders: age, gender, site and size of tumors, and histology (p =
      0.0001). The rate was 3.3% for morbidity, 1.1% for mortality, and 2.2% for
      conversion. There was no difference in complications between patients treated
      with conventional devices and those treated with the Harmonic Scalpel.
      CONCLUSIONS: The laparoscopic approach has proved to be an extremely reliable
      procedure for benign pathologies and isolated metastases. There may yet be doubts
      about its use for the treatment of adrenal carcinomas preoperatively diagnosed.
      When surgery is performed using Harmonic Scalpel, operative time is significantly
      reduced and surgery is easier and less expensive. Infact use of the Harmonic
      Scalpel allowed the cost per operation to be reduced $70. Moreover, if surgery is
      performed using the nondisposable clip applier, the expenses are reduced $105.

PMID- 11988799
TI  - Effectiveness of grasping and duration of clamping using laparoscopic graspers.
AB  - BACKGROUND: Manipulating tissue with laparoscopic forceps is more difficult than
      using the hands. This study investigates the effectiveness of grasping and the
      duration of tissue-clamping using laparoscopic forceps. METHODS: Video recordings
      of 10 laparoscopic colectomies and 15 cholecystectomies were analyzed using time
      action analysis. RESULTS: The results indicated that 62% of the grasping actions
      were successful: the tissue was clamped sufficiently to perform an action. Of all
      the clamping actions on the colon, 10% were repeated actions. On the gallbladder
      7% were repeated actions. The bowel slipped out of the grasper in 7% of the
      clamping actions, whereas the gallbladder slipped in 17%. In 89%, the colon was
      clamped less than 1 min. The maximum clamping time for colon clamps was 7 min for
      the colon, and 55 min for the gallbladder. CONCLUSION: The low percentage of
      successful grasping actions indicates that the design of laparoscopic graspers is
      not optimal.

PMID- 11988801
TI  - Malignant colonic obstruction managed by endoscopic stent decompression followed
      by laparoscopic resections.
AB  - BACKGROUND: Acute left-side colonic obstruction is a surgical emergency whose
      management is controversial. Recently metallic expandable stents have been used
      to relieve obstruction either to palliate the condition or to prepare for an
      elective surgical resection. METHODS: We propose a new minimally invasive
      therapeutic strategy for the management of malignant colonic obstructions:
      emergency endoscopic stenting followed by elective laparoscopic one-stage
      resection. The first four cases are presented. RESULTS: The stents were
      positioned successfully in all cases, and all the patients had an immediate
      restoration of bowel functions. After a period that varied from 4 to 5 days, they
      underwent a one-stage laparoscopic resection and were discharged 5 to 7 days
      after the operation. There were no postoperative complications. CONCLUSIONS:
      Malignant colonic obstruction can be managed by a sequential minimally invasive
      endolaparoscopic approach with an excellent postoperative outcome, good patient
      comfort, and a short hospital stay without the need for diverting stomas. A study
      involving a larger number of patients is needed to determine whether this
      approach is superior to traditional open surgery in terms of morbidity,
      mortality, quality of life, and recurrences.

PMID- 11988800
TI  - A new method of preemptive analgesia in laparoscopic cholecystectomy.
AB  - BACKGROUND: Although laparoscopic cholecystectomy (LC) results in less pain then
      open cholecystectomy, it is not a pain-free procedure. The aim of this study was
      to test a new method of preemptive analgesia. METHODS: By simple randomization 60
      patients were assigned to two groups (30 in each group). Group A, the placebo
      group, received 200 ml of 0.9% saline, and group B received 5 mg/kg of a local
      anesthetic solution (ropivacaine) in 200 ml of 0.9% saline. Local anesthetic or
      placebo solution were administer before creation of the pneumoperitoneum.
      RESULTS: Pain intensity, as rated by visual analog and verbal rating scales, and
      stress response data were significantly less in the group receiving ropivacaine
      than in the placebo group. No patients in treatment group received an additional
      dose of analgesic, whereas two patients in placebo group needed an additional
      analgesic. CONCLUSIONS: Our results support the clinical validity of preemptive
      analgesia, but the timing of intraperitoneal administration of local anesthetic
      is very important. Only application before creation of the pneumoperitoneum may
      preempt every neuronal central sensitization.

PMID- 11988802
TI  - The transfer of basic skills learned in a laparoscopic simulator to the operating
      room.
AB  - BACKGROUND: The aim of the study was to evaluate whether basic surgical skills
      achieved by training in LapSim, a computerbased laparoscopic simulator, could be
      transferred to the operating room. METHODS: For this study, 24 medical students
      undergoing courses in surgery were randomly assigned to train with LapSim or to
      serve as control subjects. After they had undergone simulator training 2 h per
      week for 5 weeks, their basic skills in laparoscopic surgery were assessed in a
      porcine model. The time to perform each task was measured, and four senior
      surgeons independently graded the overall performance on a 9-step differential
      rating scale. RESULTS: The participants randomized to train with LapSim showed
      significantly better results for all tasks in both parts of the study than the
      untrained participants, according to the expert evaluation. Time consumption was
      accordingly lower in the training group in the control group. CONCLUSIONS: The
      results show that basic skills achieved by systematic training with a
      laparoscopic simulator such as LapSim can be transferred to the operating room.

PMID- 11988803
TI  - Radiation stricture of rectosigmoid treated with self-expanding metallic stent.
AB  - Radiation stricture of the rectosigmoid with obstruction is a difficult clinical
      problem, and surgery is associated with high mortality and morbidity. We report a
      case involving radiation stricture of the rectosigmoid in an 80-year-old woman
      who presented with acute colonic obstruction. A self-expanding metallic stent was
      successfully inserted, and the obstruction was relieved. The stent remained
      patent for 4 months without any complications until the patient died of sepsis
      resulting from pneumonia and bedsores. The literature on the use of a metallic
      stent to manage a benign colon condition was reviewed.

PMID- 11988804
TI  - The effects of increased intraabdominal pressure on colonic anastomoses.
AB  - BACKGROUND: This experimental, randomized, controlled study was designed to
      investigate the effects of increased intraabdominal pressure (IAP) on colocolic
      anastomoses. To our knowledge, this is the first study to address this important
      issue. METHODS: For this study, 50 Wistar albino rats were randomized into five
      groups. The animals in all the groups underwent laparotomy and colocolic
      anastomosis. The rats in the control group were not subjected to increased IAP.
      Accordingly, IAP's of 14, 20, 25, and 30 mmHg were established by carbon dioxide
      insufflation and maintained for 60 min in study groups 1, 2, 3 and 4,
      respectively. Colocolic anastomosis was realized after these periods of IAP in
      the study groups. Half of the surviving rats in all the groups were sacrificed on
      postoperative days 7 and 14 to allow comparison between the control and study
      groups with respect to their mean body weights, mean anastomosis bursting
      pressures, and histopathologic characteristics of their anastomosis sites.
      RESULTS: The mean body weights of all the groups were comparable at all times
      during the study. The anastomosis bursting pressures of the animals subjected to
      increased IAP were lower than that of the control group, with the differences
      reaching statistical relevance for the animals subjected to an IAP of 20 mmHg or
      higher on postoperative day 7 (p <0.0005 for study groups 2, 3, and 4 vs the
      control group) and becoming more pronounced by the day 14 (p <0.0005 for study
      groups 2, 3, and 4 vs the control group). The anastomosis bursting pressure
      showed an inverse correlation with IAP. The adequacy of mucosal layer formation
      at the anastomosis line was lower and the degree of inflammation was higher in
      the groups exposed to an IAP of 20 mmHg or higher in the control group (p <0.05
      for both comparisons among study groups 2, 3 and 4 vs the control group).
      CONCLUSIONS: An IAP increased to 20 mmHg and higher was found to result in
      impaired strength and wound healing in colocolic anastomoses, as reflected by the
      decreased bursting pressure and mucosal layer formation, and by the increased
      inflammation at the anastomosis sites of animals subjected to high IAP values.

PMID- 11988806
TI  - Risk factors and the prevalence of trocar site herniation after laparoscopic
      fundoplication.

PMID- 11988807
TI  - Visual results in children treated for retinoblastoma.

PMID- 11988808
TI  - Phacoemulsification cataract surgery and unplanned anterior vitrectomy--is it bad
      news?
AB  - PURPOSE: The aim of this study was to determine the final visual outcome of
      patients who undergo complicated phacoemulsification cataract surgery in which
      the posterior capsule is compromised and vitrectomy was required. METHODS: Data
      were collected for patients operated on over an 18-month period from the 1st of
      January till the 24th of June 1999 at the Department of Ophthalmology, Leicester
      Royal Infirmary. All grades of surgeons were included and patients were
      identified from the theatre logbook. A standard proforma was completed and the
      data evaluated. RESULTS: A total of 2538 phacoemulsification cataract operations
      were performed over this duration. Of these, 2446 (96.4%) had uncomplicated
      phacoemulsification cataract surgery while 92 (3.6%) required anterior
      vitrectomy. In order to allow for a more accurate interpretation of the visual
      outcome, patients were divided into two groups, depending on whether or not there
      was pre-existing eye disease at initial listing.Sixty-five patients did not have
      pre-existing eye disease. From this, notes were available for 57 patients,
      whereby the best-corrected visual acuity (BCVA) was obtained postoperatively.
      Vision of 6/12 or better was used to define acceptable postoperative vision. This
      group consisted of 49 patients (86%): five had visual acuities of 6/12, 26 = 6/9,
      one = 6/7.5 and 17 = 6/6. There were eight (14%) patients with poor visual
      outcome, largely represented by patients with cystoid macular oedema (8.8%). The
      most frequent stage of vitreous loss was during primary phacoemulsification in 46
      (50%). Irrigation and aspiration, which resulted in 21 (23%) instances, followed
      this. The rate of posterior capsule rupture and anterior vitrectomy during
      phacoemulsification cataract surgery is 2% when performed by consultants, 4% by
      specialist registrars and staff grades and 10% by senior house officers.
      CONCLUSION: This study looks at the final visual outcome of patients who
      underwent unplanned anterior vitrectomy during routine phacoemulsification
      cataract surgery, in a university teaching hospital in the United Kingdom. It
      includes all levels of surgeons with varying experience. The rate of vitreous
      loss in this study for phacoemulsification cataract surgery is 3.6%. Patients who
      undergo complicated phacoemulsification cataract surgery do comparatively well.

PMID- 11988809
TI  - Macular hole surgery with silicone oil.
AB  - PURPOSE: Macular hole surgery usually involves gas tamponade which necessitates a
      variable period of postoperative posturing in a face-down position. A number of
      patients find this difficult or impossible for medical or social reasons. This
      study reviews our experience of macular hole surgery using silicone oil tamponade
      with no restriction of posturing. METHODS: Sixteen consecutive cases of macular
      hole (stage III/IV) surgery where silicone oil was used for tamponade were
      reviewed. Group A patients were unable for medical or social reasons to maintain
      a face-down posture and Group B patients had previous failed surgery with gas
      tamponade. RESULTS: Anatomical closure of hole was achieved in 81% (13/16) of all
      cases and 88% (7/8) of cases with no previous surgery (Group A) with a mean
      follow-up of 7.5 months (range 4-24 months). Mean visual improvement (log(MAR)
      value of visual acuity) for Group A and Group B were 0.41 and 0.03, respectively.
      CONCLUSIONS: The success rate of macular hole surgery using silicone oil as
      tamponade, in cases with no previous surgery, is comparable to that achieved when
      gas is used as tamponade. Although good anatomical success can be achieved in
      cases with previous failed surgery, the visual outcome is less rewarding.
      Silicone oil is an alternative to gas tamponade for macular hole surgery in
      patients who are unable or unwilling to posture. However, it has to be borne in
      mind that silicone oil tamponade is not without risks.

PMID- 11988810
TI  - Visual and symptomatic outcome of excimer phototherapeutic keratectomy (PTK) for
      corneal dystrophies.
AB  - PURPOSE: To determine the visual results and outcome of excimer laser
      phototherapeutic keratectomy (PTK) for corneal dystrophies. METHODS: Twenty-nine
      eyes of 19 patients who underwent excimer PTK for recurrent erosions and reduced
      vision due to corneal dystrophies, between February 1996 and July 1999, were
      reviewed. Data regarding the preoperative and postoperative best-corrected visual
      acuity (BCVA), change in spherical equivalent (SE), depth of excimer laser
      ablation, symptomatic relief, and incidence of recurrence were analysed by a
      retrospective chart review. RESULSTS: The range of follow-up was 12-48 months.
      Twenty-seven out of 29 eyes (93%) maintained or improved BCVA. All patients
      (17/17) were free of symptoms of recurrent erosions although two eyes needed
      repeat treatment to achieve this. In those eyes undergoing PTK for reduced
      vision, there was a trend towards a hyperopic shift postoperatively but this was
      not statistically significant. Five eyes showed recurrence of the dystrophy (Reis
      Bucklers (one eye), Lattice (two eyes), and Granular (two eyes)) that required
      repeat treatment. Two of these eyes required a single repeat PTK procedure, and
      three eyes underwent three repeat treatments. There were no major complications
      during the follow-up period. CONCLUSIONS: Excimer PTK is a safe and effective
      procedure for relieving symptoms of recurrent erosions and improving visual
      acuity in patients with corneal dystrophies. Optimal visual results are achieved
      when treating more anterior disease. Multiple treatments are possible without
      significant detrimental effects for those patients with recurrence of their
      dystrophy.

PMID- 11988811
TI  - Delayed hypersensitivity to brimonidine tartrate 0.2% associated with high
      intraocular pressure.
AB  - PURPOSE: To report the late presentation of an allergic reaction to brimonidine
      tartrate 0.2% associated with an elevation of intraocular pressure. METHODS:
      During a 6-month period six Caucasian patients (three were male), with primary
      open angle glaucoma (POAG) or ocular hypertension, with an allergic reaction to
      brimonidine tartrate eye drops were identified. Brimonidine was initiated as
      additional medical therapy in four patients and monotherapy in two patients. The
      median age of the patients was 67 years (range 57-73 years). RESULTS: There were
      nine eyes with a follicular conjunctivitis; three patients received brimonidine
      in one eye only. In two patients an additional redness of the periocular skin was
      present. The median duration on brimonidine therapy before the onset of the
      allergic reaction was 12 months (range 5-15 months). The median intraocular
      pressure (IOP) before the onset of the allergy was 18 mmHg (range 16-21 mmHg).
      There was a significant elevation of IOP at the time of the allergy with a median
      IOP of 28 mmHg (range 20-44 mmHg) (P = 0.007, Wilcoxon sign rank test). The
      cessation of brimonidine allowed the resolution of the allergic reaction. The
      intraocular pressure was then controlled with alternative medication in eight
      eyes. One patient went on to have filtering surgery. CONCLUSIONS: A delayed
      hypersensitivity reaction to brimonidine tartrate eye drops resembles a viral
      follicular conjunctivitis. It is imperative that it is recognised as such, as it
      may occur many months after brimonidine is initiated. This allergy has been found
      to be associated with a loss of control of the IOP. Though this is a small cohort
      of patients, it is not unreasonable to suggest that patients on brimonidine eye
      drops should be instructed to report promptly to their ophthalmologist the onset
      of redness of their eyes so that their glaucoma control may be reassessed.

PMID- 11988812
TI  - Effect of mechanical vs dilute ethanol epithelial removal on keratocyte apoptosis
      and polymorphonuclear leukocyte migration.
AB  - PURPOSE: To investigate keratocyte apoptosis and polymorphonuclear (PMN) cell
      infiltration to the corneal stroma after mechanical epithelial scraping and
      chemical de-epithelialization with 18% ethanol solution. METHODS: Twelve New
      Zealand Albino rabbits (24 eyes) were randomly divided into three groups. Group A
      was the control group with no epithelial removal. Group B underwent a 7.5-mm
      mechanical epithelial removal with a blunt spatula. Group C underwent 7.5-mm
      chemical de-epithelialization with 18% ethanol-balanced salt solution. Corneas
      were stained with terminal deoxyribonucleotidyl transferase-mediated dUTP
      digoxigenin nick-end labeling (TUNEL) assay after 24 h. Only nuclear staining in
      keratocytes was counted. Polymorphonuclear (PMN) leukocyte densities were also
      assessed by light microscopy. RESULTS: Mechanical de-epithelialization (group B)
      and chemical de-epithelialization with 18% ethanol (group C) showed no difference
      in keratocyte apoptosis compared with the control group. There was also no
      difference between groups B and C. Group B showed no difference in PMN leukocyte
      counts compared with the control group. But the number of PMN leukocytes observed
      in group C was significantly higher than those encountered in the corneas of the
      control group (P < 0.05) and group B (P < 0.05). CONCLUSIONS: Dilute alcohol
      induces more PMN cell infiltration when compared with mechanical de
      epithelialization although there is no difference in the apoptosis rates.

PMID- 11988813
TI  - Longitudinal study of a cohort of people with diabetes screened by the Exeter
      Diabetic Retinopathy Screening Programme.
AB  - PURPOSE: To evaluate the long-term outcome of a cohort of people with diabetes
      screened by the Exeter Diabetic Retinopathy Screening Programme. METHOD: The
      cohort comprised of diabetic patients from nine market town General Practices
      around Exeter who first attended the diabetic retinopathy screening programme in
      1992. Screening was carried out by a combination of dilated fundoscopy by a
      screening technician and a single 45 degrees Polaroid photograph of each eye. The
      prevalence of diabetic retinopathy at the baseline, the incidence of sight
      threatening diabetic retinopathy (STDR) in the next two rounds of screenings, and
      the long-term visual outcome are described. RESULTS: The cohort consisted of 775
      patients (104 Type I, 517 Type II non-insulin-requiring and 154 Type II insulin
      requiring). The mean age was 72.1 years (15-100), with mean disease duration of
      13.0 years (1-79). Baseline prevalence was as follows: background retinopathy:
      21.4%, proliferative: 2.8%, clinically significant macular oedema: 6.1%. The
      incidence of proliferative disease was 2.20% and 2.25% respectively in the next
      two rounds of screening (P > 0.05, chi2 test). The incidence of clinically
      significant macular oedema was also constant over next two rounds of screening,
      at 4.79% and 5.18% respectively (P > 0.05, chi2 test). Ninety-five (12.3%)
      patients were deceased and a further 179 (23%) patients were lost to follow-up by
      the third round. Only two patients with newly diagnosed STDR suffered
      deterioration of visual acuity to 6/60 or worse as a result of diabetic
      retinopathy. CONCLUSION: The incidence of STDR remained constant throughout the
      period of screening, reflecting the chronic progressive nature of the disease.
      Significant numbers of patients were lost to follow-up. Screening seemed
      effective in preserving vision in those patients with newly diagnosed STDR.

PMID- 11988814
TI  - Local anaesthetic endonasal endoscopic laser dacryocystorhinostomy: analysis of
      patients' acceptability and various factors affecting the success of this
      procedure.
AB  - BACKGROUND AND OBJECTIVES: Endonasal endoscopic laser dacryocystorhinostomy is
      now a well established, effective approach to relieve nasolacrimal duct
      obstruction. Whereas attempts have been made to comment on the efficacy of the
      procedure, no study has been conducted to evaluate the acceptability of this
      procedure by those at the receiving end, ie, the patients. An attempt has been
      made in the present study to critically evaluate the procedure from the point of
      view of patients' acceptability and also to evaluate certain factors which may
      influence the success rate of this procedure. PATIENTS AND METHODS: Forty-six
      eyes from 40 patients underwent endonasal endoscopic laser dacryocystorhinostomy,
      performed by the same surgeon, over a period of 15 months. Various aspects of the
      procedure were evaluated by patients by filling out a simple questionnaire
      (Figure 1). In addition to recording patients' views, success of the procedure
      was confirmed by performing a postoperative sac washout in the clinic. Patients
      were also subdivided according to their age, duration of symptoms and history of
      previous surgical intervention. The data were statistically analysed using chi
      square tests with the Yates correction. RESULTS: The percentage of patients who
      declared themselves completely cured was 65.22%. A partial resolution was felt by
      23.91% of patients and no improvement was reported by 10.87% of patients. Forty
      two out of the 46 eyes (91.3%) achieved anatomical success by the procedure, as
      shown by a postoperative sac washout performed in the clinic. Some of them,
      however, did not have complete resolution of their symptoms perhaps due to an
      additional factor of lacrimal pump dysfunction in these patients. During the
      procedure 60.86% of eyes felt no discomfort at all whereas 39.14% of eyes felt
      some discomfort at some point of time during the procedure (Table 1). When
      directly asked 86.12% of patients recommended the procedure (implying that the
      procedure had some good effect on their quality of life), 8.33% of patients did
      not recommend it and 5.55% of patients made no comments. Various factors
      affecting the success of this procedure were analysed (Table 2) and it was found
      that eyes which had no previous surgical intervention showed a complete cure rate
      which was significantly higher than that seen in eyes which had some sort of
      previous intervention (P = 0.0003); eyes with a short (<6 mths) duration of
      symptoms showed significantly higher success rates (P = 0.0098) in comparison to
      that shown by eyes with longer (>6 mths) duration of symptoms; and younger
      patients (<50 yrs) had a complete resolution rate much higher than patients over
      50 yrs of age (P = 0.0309). CONCLUSION: The present study clearly shows that
      endonasal endoscopic laser DCR is an effective procedure, well tolerated and
      recommended by the patients. Discomfort during the procedure is not a major
      problem. Younger patients, with no previous surgical intervention and with short
      duration of symptoms are likely to be benefited the most. Though success rates
      are higher with external DCR, endonasal endoscopic laser DCR offers certain
      advantages over the external approach while keeping the option of external DCR
      open, if needed at a later date.

PMID- 11988815
TI  - Psychosocial and clinical determinants of compliance with occlusion therapy for
      amblyopic children.
AB  - AIMS: The objective of this study was to determine the extent that psychosocial
      and clinical variables influence parental compliance with occlusion therapy (eye
      patching) in children with amblyopia. METHODS: Children (n = 151) receiving
      occlusion therapy (eye patching) for the treatment of amblyopia were recruited
      from five orthoptic clinics in Bristol, UK. Parents completed a questionnaire
      based on Rogers' (1983) Protection Motivation Theory (PMT). The parents (n = 105)
      were also followed up 2 months later. Clinical data, including measures of visual
      acuity, were also recorded. Compliance with eye patching was assessed through
      self-report accounts of parents. Stepwise regression analyses were used to
      determine the factors predictive of compliance with eye patching. RESULTS: Self
      reported compliance with eye patching at study entry revealed that only 54% of
      parents were achieving orthoptists' recommendations to patch their child.
      Perceived self-efficacy was positively associated with compliance and perceived
      prohibition of the child's activities were negatively associated with compliance.
      At follow-up, past behaviour accounted for the largest proportion of explained
      variance in patching behaviour followed by response efficacy, and prohibition of
      the child's activities. CONCLUSION: The present findings may serve to inform
      interventions aimed at enhancing current orthoptic practice to improve compliance
      in amblyopic children. The importance of 'self-efficacy' and past behaviour
      suggests that consultations with parents exhibiting higher levels of success with
      patching may elicit strategies that could be shared with parents experiencing
      difficulties with patching their children. In addition, it is possible that the
      perceived efficacy of the treatment could be enhanced if orthoptists emphasised
      evidence of improvements in visual acuity which may, in turn, foster the
      maintenance of eye patching.

PMID- 11988816
TI  - Effect of senescence on ocular blood flow in the retina, neuroretinal rim and
      lamina cribrosa, using scanning laser Doppler flowmetry.
AB  - PURPOSE: To determine the effects of age on blood flow measurements obtained
      using the scanning laser Doppler flowmeter (SLDF). METHOD: Using SLDF (Heidelberg
      retina flowmeter, Heidelberg Engineering, Germany) three 10 degrees images were
      taken of the superior temporal retina and three further images of the superior
      temporal neuroretinal rim in 15 young, healthy subjects (mean age 27.9 years +/-
      6.2 years) and 15 mature, healthy subjects (mean age 65.2 years +/- 13.7 years).
      In addition, measurements were taken of the lamina cribrosa in 12 of the
      volunteers from each subject group (mean age 27.1 +/- 6.3 years and 64.8 +/- 13.2
      years respectively). Using a 10 x 10 pixel measurement frame, blood flow readings
      were obtained at a predetermined position on the retina, neuroretinal rim and
      lamina cribrosa. Student's two-tailed unpaired t-tests were used to compare
      measures of blood flow, volume and velocity between the two subject groups (P <
      0.05). In addition, linear regression analysis was used to assess the
      relationship between age and blood flow, volume and velocity at the retina,
      neuroretinal rim and lamina cribrosa. RESULTS: Retinal blood volume measured at
      the retina was significantly lower in the mature compared with the young subject
      group (P = 0.01). Mature subjects also exhibited reduced blood flow and velocity
      at the neuroretinal rim (P = 0.01 for both parameters) and lamina cribrosa (P =
      0.008 and P = 0.01 respectively). Regression analysis revealed negative trends
      for all blood flow parameters in each of the anatomical areas with advancing age.
      Significant negative correlations were obtained for retinal blood volume (r = 
      0.455, P < 0.05), neuroretinal rim blood velocity (r = -0.359, P < 0.05) and
      lamina cribrosa blood volume (r = -0.475, P < 0.05). CONCLUSION: Capillary blood
      flow in the retina, neuroretinal rim and lamina cribrosa decreases with advancing
      age. This may be of consequence in the progression of chronic ocular diseases
      such as glaucoma, and should be considered in the longitudinal determination of
      change in disease monitoring.

PMID- 11988817
TI  - Comparison of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels with
      grades of retinopathy in patients with diabetes mellitus.
AB  - BACKGROUND: Vitreal interleukin (IL)-1beta (IL-1beta), IL-6, IL-8, tumor necrosis
      factor-alpha (TNF-alpha) and nitric oxide (NO) levels have previously been
      determined in patients with proliferative diabetic retinopathy (PDR). However, at
      present there is no cohort study linking serum levels of NO and many inflammatory
      cytokines such as TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 and
      IL-8 to the grade of the microvascular complications. PURPOSE: To determine the
      relation between the stages of DR and the levels of serum NO, TNF-alpha, IL
      1beta, sIL-2R, IL-6 and chemokine IL-8 in patients with diabetes compared with
      healthy controls. METHODS: Fifty-three consecutive patients with diabetes (25
      men, 28 women) with or without DR and 15 non-diabetic healthy subjects (seven
      men, eight women) as controls were included in this prospective study. As an
      indicator for NO, serum total nitrite (NO2- + NO3-) levels (end-product of NO)
      were measured by the Griess reaction. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and
      IL-8 levels were determined by a spectrophotometric technique using an Immulite
      chemiluminescent immunometric assay. The patients with diabetes were classified
      into three groups according to the stage of DR: no DR (NDR; n = 16), non
      proliferative DR (NPDR; n = 18) and PDR (n = 19). The data were analysed using a
      Mann-Whitney U-test and the results were expressed as mean +/- SE (range).
      RESULTS: The levels of IL-1beta and IL-6 were below the detection limits of the
      assay (for each, <5.0 pg/ml) in all patients with diabetes and controls. Soluble
      IL-2R levels ranged from 260 to 958 U/ml, with the highest values observed in the
      patients with PDR. In 47 of the 53 samples (89%) tested for diabetic patients, IL
      8 levels were above the detection limits of the assay (5.0 pg/ml). IL-8 levels
      ranged from <5.0 to 25.0 pg/ml, with the highest mean values observed in PDR
      patients. TNF-alpha was detectable in 46 of 53 patients with diabetes (87%),
      ranging from <4.0 to 26.4 pg/ml, with again the highest values obtained in the
      patients with PDR. Serum NO levels ranged from 80 to 188 micromol/l, with the
      highest values obtained in patients with PDR. Taken together, the mean serum NO,
      sIL-2R, IL-8 and TNF-alpha levels increased with the stage of DR and the highest
      levels were found in patients with PDR. The PDR patients had significantly (for
      each, P < 0.001) higher serum NO (166.8 +/- 3.2 micromol/l), sIL-2R (807.9 +/-
      33.3 U/ml), IL-8 (17.9 +/- 0.4 pg/ml) and TNF-alpha (15.0 +/- 0.8 pg/ml) levels
      compared with NPDR patients (149.5 +/- 2.1, 659.4 +/- 23.4, 12.9 +/- 1.1, 11.5 +/
      0.6, respectively), NDR patients (115.9 +/- 5.8, 373.8 +/- 15.0, 8.3 +/- 1.0,
      6.6 +/- 0.9, respectively) and controls (116.6 +/- 2.3, 392.4 +/- 16.6, 7.2 +/-
      0.3, 7.3 +/- 0.5, respectively). Serum levels of these parameters for NPDR
      patients were also significantly (for each, P < 0.01) higher compared with those
      of NDR patients and controls. On the other hand, serum NO, sIL-2R, IL-8 and TNF
      alpha levels of patients with NDR were comparable with those of controls (for
      each, P > 0.05). CONCLUSION: The results of the present study suggest that NO,
      sIL-2R, IL-8 and TNF-alpha may play important roles in the pathophysiology and
      progression of DR. We think that these potentially inflammatory cytokines and NO
      with their endothelial implications may act together during the course and
      progression of DR. These molecules may serve as therapeutic targets for the
      treatment and/or prevention of diabetes with its systemic and ocular
      microvascular complications.

PMID- 11988818
TI  - Long-term effect on optic nerve of silicone oil tamponade in rabbits:
      histological and EDXA findings.
AB  - PURPOSE: Side-effects after intravitreal use of silicone oil (SO) are not well
      defined and elucidated. The object of this study was to examine the influence and
      toxicity of SO on the optic nerve after vitrectomy with SO tamponade. METHODS: We
      injected medical grade SO and emulsified SO into rabbit eyes after gas-mediated
      vitreous compression and examined the eyes by light microscopy (LM), transmission
      electron microscopy (TEM) and energy dispersive X-ray analysis (EDXA) (point
      analysis and area analysis) 6 months after injection. We compared the findings in
      the non-treated eyes and eyes with only gas-mediated vitreous compression with
      those in SO-injected eyes. RESULTS: Vacuole-like structures were seen in the
      optic nerve posterior to the lamina cribrosa. In the group treated with only gas
      mediated vitreous compression, the myelin structures were shown by TEM to be
      destroyed and replaced by glial tissue, while in groups injected with medical
      grade or emulsified SO severe destruction of the myelin sheath (myelinolysis) was
      observed. Silicone was identified at the electron-dense edges of the vacuoles by
      EDXA point analysis, but not in the vacuoles without electron-dense deposits.
      Dots of Si K alpha were not seen in the control groups, and dense dots were
      observed in SO-injected groups, by EDXA area analysis. CONCLUSIONS: Some of the
      vacuoles might be artefacts caused by insufficient fixation or the operative
      procedure, but TEM showed almost no artefacts in the control optic nerve. Thus,
      most vacuoles may be SO storage sites. SO uptake into the optic nerve might play
      a role in the pathogenesis of optic nerve atrophy after SO injection.

PMID- 11988819
TI  - Congenital nuclear cataracts and uveitis in HIV-transgenic mice.
AB  - PURPOSE: Patients infected with HIV-1 develop ocular manifestations, some due to
      opportunistic infections and others attributed to the virus itself. Among the
      latter are retinal microvasculopathy and uveitis. We have analysed the ocular
      phenotype in HIV-transgenic mice. METHODS: We have studied T26 transgenic mice
      which bear a gag-pol deleted HIV-1 genome. Transgene RNA was detected by Northern
      analysis. Ocular pathology was assessed by conventional histology, immunostaining
      for gp120 envelope protein, and in situ apoptosis detection with end-labelling.
      RESULTS: Abnormalities of lens epithelial cell development were detected as early
      as embryonic day 14.5. Histological changes included the malformation of an
      embryonal lens nucleus and poor closure of the lens suture lines. This resulted
      in congenital nuclear cataracts, as occur in congenital viral infections in human
      patients. In the adult animals, lenses were notable for extensive vacuolation,
      liquefaction, and degeneration of the cortex. Mild iridocyclitis and vitritis
      were also noted in adult transgenic mice. Immunostaining demonstrated the
      expression of gp 120 envelope protein within the lens epithelial and fibre cells.
      End-labelling with terminal deoxyribonucleotidyl transferase showed increased
      numbers of apoptotic cells in the adult lens. CONCLUSIONS: These findings suggest
      that one or more HIV-1 proteins are associated with congenital nuclear cataract
      formation and uveitis in HIV-transgenic mice.

PMID- 11988820
TI  - Two unusual cases of visual loss following severe non-surgical blood loss.

PMID- 11988821
TI  - Possible cat scratch disease causing neuroretinitis and CRVO in a child.

PMID- 11988822
TI  - Spontaneous orbital haemorrhage in purpura fulminans secondary to meningococcal
      septicaemia.

PMID- 11988823
TI  - Premacular gliosis in a patient with tuberose sclerosis.

PMID- 11988824
TI  - Unexpected visual improvement with a pinhole in central retinal artery occlusion
      and cilioretinal artery sparing fovea.

PMID- 11988825
TI  - Aspergillus iris granuloma in an immunocompetent individual.

PMID- 11988826
TI  - E-Cadherin distribution in normal and dysplastic conjunctival epithelium.

PMID- 11988828
TI  - Acute myeloid leukaemia presenting as retinal vein occlusion and eyelid swelling.

PMID- 11988827
TI  - Orbital cellulitis following sub-Tenon's anaesthesia.

PMID- 11988829
TI  - Solar retinopathy after the 1999 solar eclipse in East Sussex.

PMID- 11988830
TI  - Visual field loss and Alzheimer's disease.

PMID- 11988831
TI  - Subclinical hypothyroidism--increased awareness may prevent unnecessary treatment
      and morbidity.

PMID- 11988832
TI  - Severe progression of glaucomatous optic neuropathy in patients with Alzheimer's
      disease.

PMID- 11988833
TI  - Uncomplicated phacoemulsification--should we see our patients the following day?

PMID- 11988835
TI  - 'Lost' metallic vitrectomy port scleral plugs and MRI scanning.

PMID- 11988836
TI  - Purulent orbital cellulitis.

PMID- 11988837
TI  - c-Myc oncoprotein: a dual pathogenic role in neoplasia and cardiovascular
      diseases?
AB  - A growing body of evidence indicates that c-Myc can play a pivotal role both in
      neoplasia and cardiovascular diseases. Indeed, alterations of the basal machinery
      of the cell and perturbations of c-Myc-dependent signaling network are involved
      in the pathogenesis of certain cardiovascular disorders. Down-regulation of c-Myc
      induced by intervention with antioxidants or by antisense technology may protect
      the integrity of the arterial wall as well as neoplastic tissues. Further
      intervention studies are necessary to investigate the effects of tissue-specific
      block of c-Myc overexpression in the development of cardiovascular diseases.

PMID- 11988838
TI  - The role of alpha(v)beta(3) in prostate cancer progression.
AB  - Integrin alpha(v)beta(3) is involved in varied cell biological activities,
      including angiogenesis, cell adhesion, and migration on several extracellular
      matrix components. Although alpha(v)beta(3) is not typically expressed in
      epithelial cells, it is expressed in macrophages, activated leukocytes, cytokine
      stimulated endothelial cells, osteoclasts, and certain invasive tumors.
      Interestingly, the adhesion and migration of breast cancer cells on bone matrix
      are mediated, in part, by alpha(v)beta(3). Similar to breast cancer cells,
      prostate cancer cells preferentially metastasize to the bone. The biological
      events that mediate this metastatic pattern of prostate cancer are not well
      defined. This review discusses the role alpha(v)beta(3) plays in prostate cancer
      progression, with specific emphasis on bone metastasis and on alpha(v)beta(3)
      signaling in prostate cancer cells. The data suggest that alpha(v)beta(3), in
      part, facilitates prostate cancer metastasis to bone by mediating prostate cancer
      cell adhesion to and migration on osteopontin and vitronectin, which are common
      proteins in the bone microenvironment. These biological events require the
      activation of focal adhesion kinase and the subsequent activation of PI-3
      kinase/Akt signaling pathway.

PMID- 11988839
TI  - The human p73 promoter: characterization and identification of functional E2F
      binding sites.
AB  - p73, a member of the p53 family, is overexpressed in many cancers. To understand
      the mechanism(s) underlying this overexpression, we have undertaken a detailed
      characterization of the human p73 promoter. The promoter is strongly activated in
      cells expressing exogenous E2F1 and suppressed by exogenous Rb. At least three
      functional E2F binding sites, located immediately upstream of exon 1 (at -284, 
      155 and -132) mediate this induction. 5' serially deleted promoter constructs and
      constructs harboring mutated E2F sites were analyzed for their response to
      exogenously expressed E2F1 or Rb to establish functionality of these sites.
      Authenticity of E2F sites was further confirmed by electrophoretic mobility shift
      assay (EMSA) using E2F1/DP1 heterodimers synthesized in vitro, followed by
      competition assays with unlabeled wild-type or mutant oligonucleotides and
      supershift analysis using anti-E2F1 antibodies. In vivo binding of E2F1 to the
      p73 promoter was demonstrated using nuclear extracts prepared from E2F1-inducible
      Saos2 cells. The region conferring the highest promoter activity was found to
      reside between -113 to -217 of the p73 gene. Two of the three functional E2F
      sites (at -155 and -132) reside within this region. Our results suggest that
      regulation of p73 expression is primarily mediated through binding of E2F1 to
      target sites at -155 and -132.

PMID- 11988840
TI  - Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic
      factors and cancer progression in breast epithelial cells.
AB  - Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is
      associated with the risk and progression of many types of cancer, although
      despite this it remains unclear how activated IGF-1R contributes to cancer
      progression. In this study, gene expression changes elicited by IGF-1 were
      profiled in breast epithelial cells. We noted that many genes are functionally
      linked to cancer progression and angiogenesis. To validate some of the changes
      observed, the RNA and/or protein was confirmed for c-fos, cytochrome P450 1A1,
      cytochrome P450 1B1, interleukin-1 beta, fas ligand, vascular endothelial growth
      factor, and urokinase plasminogen activator. Nuclear proteins were also
      temporally monitored to address how gene expression changes were regulated. We
      found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT,
      hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element
      binding protein, which correlated with temporal changes in gene expression. Next,
      the promoter regions of IGF-1-regulated genes were searched in silico. The
      promoters of genes that clustered together had similar regulatory regions. In
      summary, IGF-1 inscribes a gene expression profile relevant to cancer
      progression, and this study provides insight into the mechanism(s) whereby some
      of these changes occur.

PMID- 11988841
TI  - Proteasomal degradation of human peptidyl prolyl isomerase pin1-pointing phospho
      Bcl2 toward dephosphorylation.
AB  - Microtubule inhibitor-induced Bcl2 phosphorylation is detrimental to its
      antiapoptotic function. Phosphorylation of Bcl2 predominantly occurs on two
      serine residues (70 and 87) in cells arrested at G2-M phase by microtubule
      disarraying agents. Phospho Bcl2 can associate with a cis-trans peptidyl prolyl
      isomerase, Pin1. Pin1 and its homologues are known to target the proline residue
      carboxyl terminal to the phosphorylated threonine or serine residue of mitotic
      phosphoproteins, such as Bcl2. However, it was not clear how an extranuclear
      protein could associate with nuclear Pin1. The confocal images of the
      immunofluorescence studies employing phospho Bcl2-specific antibody developed in
      the laboratory demonstrated the translocation of phospho Bcl2 inside the nucleus.
      Interestingly, proteasomal degradation of Pin1 facilitates dephosphorylation of
      phospho Bcl2 due to longer exposure of Taxol. Here we show for the first time
      that proteasomal degradation of Pin1 is the key factor to determine the fate of
      phosphoforms of Bcl2. When Pin1 is degraded by proteasomes, phospho Bcl2 is
      converted to its native form. Thus, transient conformational change of Bcl2 due
      to association with peptidyl prolyl isomerase can contribute to irreversible
      apoptotic signaling.

PMID- 11988842
TI  - Cellular activation of the self-quenched fluorescent reporter probe in tumor
      microenvironment.
AB  - The effect of intralysosomal proteolysis of near-infrared fluorescent (NIRF) self
      quenched macromolecular probe (PGC-Cy5.5) has been previously reported and used
      for tumor imaging. Here we demonstrate that proteolysis can be detected
      noninvasively in vivo at the cellular level. A codetection of GFP fluorescence
      (using two-photon excitation) and NIRF was performed in tumor-bearing animals
      injected with PGC-Cy5.5. In vivo microscopy of tumor cells in subdermal tissue
      layers (up to 160 microm) showed a strong Cy5.5 dequenching effect in GFP
      negative cells. This observation was corroborated by flow cytometry, sorting, and
      reverse transcription polymerase chain reaction analysis of tumor-isolated cells.
      Both GFP-positive (81% total) and GFP-negative (19% total) populations contained
      Cy5.5-positive cells. The GFP-negative cells were confirmed to be host mouse
      cells by the absence of rat cathepsin mRNA signal. The subfraction of GFP
      negative cells (2.5-3.0%) had seven times higher NIRF intensity than the majority
      of GFP-positive or GFP-negative cells (372 and 55 AU, respectively). Highly NIRF
      positive, FP-negative cells were CD45- and MAC3-positive. Our results indicate
      that: 1) intracellular proteolysis can be imaged in vivo at the cellular level
      using cathepsin-sensitive probes; 2) tumor-recruited cells of hematopoetic origin
      participate most actively in uptake and degradation of long-circulating
      macromolecular probes.

PMID- 11988843
TI  - Antitumor effect of MAb EMD 55900 depends on EGF-R expression and histopathology.
AB  - The proliferative stimulus of the epidermal growth factor (EGF) in human
      epithelial cells is mediated by its binding to the external domain of the EGF
      receptor (EGF-R). The purpose of this study was to investigate whether growth
      arrest of tumors treated with anti-EGF-R MAb (EMD 55900) was dependent on EGF-R
      expression and distinct histopathologic criteria of those neoplasms. Nine
      different adenocarcinomas, squamous cell carcinomas and two neoplastic epithelial
      cell lines (A431 and Detroit 562), which were characterized by high EGF-R
      expression, were xenotransplanted onto NMRI-nu/nu mice and treated with an anti
      EGF-R antibody (EMD 55900). Results revealed that EGF-R expression and distinct
      histopathologic growth patterns play an important role for the therapeutic effect
      of the EGF-R antibody treatment. Tumors with high epithelial cellularity and
      little connective tissue responded to EMD 55900 treatment to a greater degree of
      growth reduction than tumors with lower cellularity. These results will be
      helpful for evaluation of patients who would benefit from tumor therapy with anti
      EGF-R antibody.

PMID- 11988844
TI  - Different phenotypes in human prostate cancer: alpha6 or alpha3 integrin in cell
      extracellular adhesion sites.
AB  - The distribution of alpha6/alpha3 integrin in adhesion complexes at the basal
      membrane in human normal and cancer prostate glands was analyzed in 135 biopsies
      from 61 patients. The levels of the polarized alpha6/alpha3 integrin expression
      at the basal membrane of prostate tumor glands were determined by quantitative
      immunohistochemistry. The alpha6/alpha3 integrin expression was compared with
      Gleason sum score, pathological stage, and preoperative serum prostate-specific
      antigen (PSA). The associations were assessed by statistical methods. Eighty
      percent of the tumors expressed the alpha6 or alpha3 integrin and 20% was
      integrin-negative. Gleason sum score, but not serum PSA, was associated with the
      integrin expression. Low Gleason sum score correlated with increased integrin
      expression, high Gleason sum score with low and negative integrin expression.
      Three prostate tumor phenotypes were distinguished based on differential integrin
      expression. Type I coexpressed both alpha6 and alpha3 subunits, type II
      exclusively expressed alpha6 integrin, and type III expressed alpha3 integrin
      only. Fifteen cases were further examined for the codistribution of vinculin,
      paxillin, and CD 151 on frozen serial sections using confocal laser scanning
      microscopy. The alpha6/alpha3 integrins, CD151, paxillin, and vinculin were
      present within normal glands. In prostate carcinoma, alpha6 integrin was
      colocalized with CD 151, but not with vinculin or paxillin. In tumor phenotype I,
      the alpha6 subunit did not colocalize with the alpha subunit indicating the
      existence of two different adhesion complexes. Human prostate tumors display on
      their cell surface the alpha6beta1 and/or alpha3beta1 integrins. Three tumor
      phenotypes associated with two different adhesion complexes were identified,
      suggesting a reorganization of cell adhesion structures in prostate cancer.

PMID- 11988845
TI  - Early response of prostate carcinoma xenografts to docetaxel chemotherapy
      monitored with diffusion MRI.
AB  - For many anticancer therapies, it would be desirable to accurately monitor and
      quantify tumor response early in the treatment regimen. This would allow
      oncologists to continue effective therapies or discontinue ineffective therapies
      early in the course of treatment, and hence, reduce morbidity. This is especially
      true for second-line therapies, which have reduced response rates and increased
      toxicities. Previous works by others and ourselves have shown that water
      mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI),
      increases early in tumors destined to respond to therapies. In the current
      communication, we further characterize the utility of DW-MRI to predict response
      of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting.
      The current data illustrate that tumor volumes and secreted prostate-specific
      antigen both respond strongly to docetaxel in a dose-responsive manner, and the
      apparent diffusion coefficient of water (ADC(w)) increases significantly by 2
      days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram
      analyses. Our results indicate that DW-MRI can be used for early detection of
      prostate carcinoma xenograft response to docetaxel chemotherapy.

PMID- 11988846
TI  - Acute effects of vascular modifying agents in solid tumors assessed by
      noninvasive laser Doppler flowmetry and near infrared spectroscopy.
AB  - The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared
      spectroscopy (NIRS) to detect acute effects of different vascular-modifying
      agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary
      carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice were treated
      with flavone acetic acid (FAA, 150 mg/kg), 5,6-dimethylxanthenone-4-acetic acid
      (DMXAA, 20 mg/kg), combretastatin A-4 disodium phosphate (CA4DP, 250 mg/kg),
      hydralazine (HDZ, 5 mg/kg), or nicotinamide (NTA, 500 mg/kg). Tumor perfusion
      before and after treatment was evaluated by noninvasive LDF, using a 41 degrees C
      heated custom-built LDF probe with four integrated laser/receiver units, and
      tumor blood volume was estimated by NIRS, using light guide coupled reflectance
      measurements at 800+/-10 nm. FAA, DMXAA, CA4DP, and HDZ significantly decreased
      tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA,
      and HDZ significantly reduced the blood volume within the tumor, indicating that
      these compounds to some degree shunted blood from the tumor to adjacent tissue,
      HDZ being most potent. CA4DP caused no change in the tumor blood volume,
      indicating that the mechanism of action of CA4DP was vascular shut down with the
      blood pool trapped in the tumor. NTA caused no change in either tumor perfusion
      or tumor blood volume. We conclude that noninvasive LDF and NIRS can determine
      acute effects of vascular modifying agents on tumor perfusion and blood volume.

PMID- 11988848
TI  - The Breast Cancer Research Foundation; a cure in our lifetime.

PMID- 11988847
TI  - Cyclin K as a direct transcriptional target of the p53 tumor suppressor.
AB  - Cyclin K, a newly recognized member of the "transcription" cyclin family, may
      play a dual role by regulating CDK and transcription. Using cDNA microarray
      technology, we found that cyclin K mRNA was dramatically increased in U373MG, a
      glioblastoma cell line deficient in wild-type p53, in the presence of exogenous
      p53. An electrophoretic mobility-shift assay showed that a potential p53-binding
      site (p53BS) in intron 1 of the cyclin K gene could indeed bind to p53 protein.
      Moreover, a heterologous reporter assay revealed that the p53BS possessed p53
      dependent transcriptional activity. Colony-formation assays indicated that
      overexpression of cyclin K suppressed growth of T98G, U373MG and SW480 cells. The
      results suggested that cyclin K may play a role in regulating the cell cycle or
      apoptosis after being targeted for transcription by p53.

PMID- 11988849
TI  - Oxidative stress, plant-derived antioxidants and liver fibrosis.
AB  - There is accumulating evidence that oxidative stress plays a considerable role in
      the development of liver fibrosis by acting in different cell types and in
      different signaling pathways. Consequently, antioxidants, particularly those of
      plant origin, have emerged as potent antifibrotic agents. This review briefly
      summarizes current views of the mechanisms of fibrogenesis and recent findings on
      the antifibrotic potential of plant-derived antioxidants.

PMID- 11988850
TI  - Protodioscin (NSC-698 796): its spectrum of cytotoxicity against sixty human
      cancer cell lines in an anticancer drug screen panel.
AB  - Protodioscin (NSC-698 796) is a furostanol saponin isolated from the rhizome of
      Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for
      the treatment of cervical carcinoma, carcinoma of urinary bladder and renal tumor
      for centuries. To systematically evaluate its potential anticancer activity,
      protodioscin was tested for cytotoxicity in vitro against 60 human cancer cell
      lines in the NCI's (National Cancer Institute, USA) anticancer drug screen. As a
      result, protodioscin was cytotoxic against most cell lines from leukemia and
      solid tumors in the NCI's human cancer panel, especially selectively against one
      leukemia line (MOLT-4), one NSCLC line (A549/ATCC), two colon cancer lines (HCT
      116 and SW-620), one CNS cancer line (SNB-75), one melanoma line (LOX IMVI), and
      one renal cancer line (786 - 0) with GI50 < or = 2.0 microM. In the general view
      of mean graphs, leukemia, colon cancer and prostate cancer are the most sensitive
      subpanels, while ovarian cancer is the least sensitive subpanel. Based on an
      analysis of COMPARE computer program with protodioscin as a seed compound, no
      compounds in the NCI's anticancer drug screen database have cytotoxicity patterns
      (mean graphs) similar to those of protodioscin, indicating that a potential novel
      mechanism of anticancer action is involved.

PMID- 11988851
TI  - Effect of baicalein on apoptosis of the human Hep G2 cell line was induced by
      mitochondrial dysfunction.
AB  - The effects of baicalein on the human hepatoblastoma G2 (Hep G2) cell line were
      investigated in this study. By an SRB viability assay, we demonstrated that
      baicalein reduced the viability in a dose- and time-dependent manner. The
      apoptotic features such as chromatin condensation and DNA fragmentation were
      observed in the baicalein-treated cells. During the process of apoptosis, we
      noticed a sequential dissipation of mitochondrial membrane potential (DeltaPsim)
      and an apparent redistribution of cytochrome c from the mitochondria to the
      cytosol in baicalein-treated cells. Furthermore, the mitochondrial Bcl-2 protein
      represented a dramatic change in response to baicalein treatment. Altogether, our
      data suggested that the effect of baicalein on apoptosis of the human Hep G2 cell
      line was induced by mitochondrial dysfunction and Bcl-2 regulation.

PMID- 11988852
TI  - Cardiovascular effects of isorhamnetin and quercetin in isolated rat and porcine
      vascular smooth muscle and isolated rat atria.
AB  - Isorhamnetin and quercetin produced endothelium-independent vasodilator effects
      in rat aorta, rat mesenteric arteries, rat portal vein and porcine coronary
      arteries. The effects of the two flavonoids were similar in arteries stimulated
      by noradrenaline, KCl, U46619 or phorbol esters but the two flavonoids were more
      potent in the coronary arteries than in the aorta. At high concentrations, they
      also induced a positive inotropic effect in isolated rat atria. Therefore, at
      least part of the in vivo effects of quercetin may result from its conversion to
      isorhamnetin which is the main metabolite of quercetin found in plasma. The
      arterial, venous and coronary vasodilator effects may contribute to the
      protective effects of flavonoids in ischaemic heart disease observed in
      epidemiological studies.

PMID- 11988853
TI  - Anti-inflammatory triterpenes from Pistacia terebinthus galls.
AB  - From the galls of Pistacia terebinthus we obtained an extract that proved to be
      effective against chronic and acute inflammation. Now we report on the isolation
      and identification of three triterpenes: two tirucallane-type lanostanoids and
      one oleanane, which we have identified as masticadienonic acid (1),
      masticadienolic acid (2), and morolic acid (3), respectively. All of them showed
      effectiveness on the mouse ear inflammation induced by repeated applications of
      12-O-tetradecanoylphorbol 13-acetate and on the phospholipase A2-induced foot paw
      edema. The pharmacological activity of the compounds was ratified by a
      histological study of the ear samples. In addition, they inhibited leukotriene B4
      production in rat polymorphonuclear leukocytes stimulated with calcium ionophore
      A 23187.

PMID- 11988854
TI  - Effects of Ginkgetin from Ginkgo biloba Leaves on cyclooxygenases and in vivo
      skin inflammation.
AB  - Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a
      phospholipase A2 inhibitor and this compound showed the potent antiarthritic
      activity in rat adjuvant-induced arthritis as well as analgesic activity. This
      investigation was carried out to find effects on cyclooxygenase (COX)-1 and -2
      including an in vivo effect. Ginkgetin (1 - 10 microM) and the biflavonoid
      mixture (10 - 50 microg/ml), mainly a 1 : 1 mixture of ginkgetin and
      isoginkgetin, from G. biloba leaves, inhibited production of prostaglandin E2
      from lipopolysaccharide-induced RAW 264.7 cells. This inhibition was mediated, at
      least in part, by down-regulation of COX-2 expression, but not by direct
      inhibition of COX-1 or COX-2 activity. Down-regulation of COX-2 by ginkgetin was
      also proved in the dorsal skin of ICR mouse treated by 12-O-tetradecanoylphorbol
      13-acetate (TPA). At total doses of 1,000 microg/site on the dorsal skin (15 mm x
      15 mm), ginkgetin inhibited prostaglandin E2 production by 65.6 % along with a
      marked suppression of COX-2 induction. In addition, ginkgetin and the biflavonoid
      mixture (100 - 1,000 microg/ear) dose-dependently inhibited skin inflammation of
      croton oil induced ear edema in mice by topical application. The present study
      suggests that ginkgetin from G. biloba leaves down-regulates COX-2 induction in
      vivo and this down-regulating potential is associated with an anti-inflammatory
      activity against skin inflammatory responses.

PMID- 11988855
TI  - Inhibitory effect of N(G)-nitro-L-arginine methyl ester on the anti-adrenergic
      response elicited by ayanin in the pithed rat.
AB  - In this study we evaluated the anti-adrenergic response elicited by ayanin, a
      flavonoid compound isolated from Croton schiedeanus Schlecht, in the pithed rat,
      and the inhibitory effect of NO synthase inhibitor N(G)-nitro-L-arginine methyl
      ester (L-NAME), and its acute toxicity profile in mice. In pithed rats ayanin (5 
      50 mg/kg i. v.) caused a dose-dependent decrease in the pressor and chronotropic
      responses induced by intravenous noradrenaline administration (0.25 microg/kg).
      This anti-adrenergic response was completely abolished by prior treatment with L
      NAME (10 mg/kg i.v ) and the inhibitory effect of L-NAME was reversed after
      intravenous administration of L-arginine (100 mg/kg, i. v.). No lethal or major
      toxic effects were observed in mice receiving i. p. administration of ayanin up
      to a dose of 500 mg/kg. Our findings confirm that ayanin exerts protective
      cardiovascular effects against the increase in blood pressure and heart rate
      mainly through a mechanism that depends on the NO/cyclic guanosine monophosphate
      (cGMP) pathway without acute toxic effects. These results suggest that extracts
      of Croton schiedeanus, the native south American plant from which ayanin was
      isolated, might be beneficial in cardiovascular disease.

PMID- 11988856
TI  - The effects of higenamine on LPS-induced experimental disseminated intravascular
      coagulation (DIC) in rats.
AB  - The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots
      of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation
      (DIC), was investigated using an experimental DIC rat model. The oral
      administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated
      the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin
      degradation product (FDP) level, and the prolongation of prothrombin time (PT)
      induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of
      activated partial thrombin time (aPTT) and the decrease of platelet count were
      suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea
      nitrogen (BUN) were also significantly prevented with higenamine. The above
      results are suggestive that higenamine has therapeutic potential for DIC and/or
      accompanying multiple organ failure (MOF).

PMID- 11988857
TI  - Angiogenic activity of beta-sitosterol in the ischaemia/reperfusion-damaged brain
      of Mongolian gerbil.
AB  - Aloe vera continues to be used for wound healing as a folk medicine. We
      previously reported that A. vera gel has angiogenic activity. In this study, we
      report upon the isolation of an angiogenic component beta-sitosterol from A. vera
      and examination of its effect upon damaged blood vessels of the Mongolian gerbil.
      In a chick embryo chorioallantoic membrane assay, beta-sitosterol was found to
      have an angiogenic effect. It enhanced new vessel formation in gerbil brains
      damaged by ischaemia/reperfusion, especially in the cingulated cortex and septal
      regions, in a dose-dependent fashion (up to 500 microg/kg, p < 0.05, n = 34 -
      40). beta-Sitosterol also enhanced the expressions of proteins related to
      angiogenesis, namely von Willebrand factors, vascular endothelial growth factor
      (VEGF), VEGF receptor Flk-1, and blood vessel matrix laminin (p < 0.05, n = 6).
      In addition, the intraperitoneal administration of beta-sitosterol at 500
      microg/kg/day for a period of 19 days significantly improved the motion recovery
      of ischaemia/reperfusion-damaged gerbils as assessed by rota-rod testing (p <
      0.001, n = 10). Our results suggest that beta-sitosterol has therapeutic
      angiogenic effects on damaged blood vessels.

PMID- 11988858
TI  - Production of paclitaxel and baccatin III in a 20-L airlift bioreactor by a cell
      suspension of Taxus wallichiana.
AB  - A cell suspension culture of Taxus wallichiana (Himalayan Yew) was grown in shake
      flasks and a 20-L airlift bioreactor running for 28 days in a batch mode, and its
      capacity to accumulate paclitaxel and baccatin III was measured. When both
      culture types were in the highest productive state (from day 24 to day 28), there
      was a greater accumulation of paclitaxel and baccatin III in the bioreactor
      culture than in the shake flask culture (factor of 2.0 and 1.2, respectively).
      These increases in paclitaxel and baccatin III production cannot be related to
      the difference observed between the growth rates of both cultures, because when
      the bioreactor culture was at maximum productivity, its cell biomass, expressed
      in g L(-1) of dry weight, was similar to that obtained in the shake flask
      culture. It seems that these improvements were mainly due to adequate aeration
      and mixing of the culture in the bioreactor. The maximum yield observed for
      paclitaxel (20.84 mg x L(-1) day 24) and baccatin III (25.67 mg x L(-1) day 28)
      represents a productivity of 0.90 mg x L(-1) d(-1) and 0.93 mg x L(-1) x d(-1)
      respectively.

PMID- 11988859
TI  - Evaluation of Podophyllum peltatum accessions for podophyllotoxin production.
AB  - In an effort to develop a sustainable source of podophyllotoxin for the
      production of anticancer drugs such as etoposide, teniposide and etopophos,
      Podophyllum peltatum accessions with podophyllotoxin-rich leaf biomass were
      identified and transplanted to different growing conditions by vegetative
      cuttings. Results indicate that the lignan profile in leaves does not change over
      time or due to environment conditions. Podophyllotoxin and alpha-peltatin content
      in the blades seems to be stable with an inverse relationship of concentration
      between these compounds. A podophyllotoxin-rich leaf accession showed low
      biosynthetic capability to synthesize alpha- and beta-peltatin and the converse
      was also true, indicating that selection and cultivation of high-yielding
      podophyllotoxin leaf biomass may reduce production costs.

PMID- 11988860
TI  - (3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-perhydro-1,4-oxazine-2,5-dione:
      an apoptosis-inducer from the fruiting bodies of Isaria japonica.
AB  - (3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethylperhydro-1,4-oxazine-2,5-dione
      (1) was isolated from the fruiting bodies of Isaria japonica as an apoptosis
      inducing agent. The complete structural assignment of the compound was
      accomplished on the basis of spectroscopic methods and chemical transformations.
      Compound 1 induced apoptotic cell death of the human leukemia cells (HL-60) in a
      dose-dependent manner, ranging from 5.0 microg/ml to 100.0 microg/ml.

PMID- 11988861
TI  - Complete LC/MS analysis of a Tinnevelli senna pod extract and subsequent
      isolation and identification of two new benzophenone glucosides.
AB  - The hydroalcoholic extract of Tinnevelli senna is widely used as a laxative
      phytomedicine. In order to improve the knowledge of the chemical composition of
      this extract, LC/MS and LC/MS(n) studies were performed, allowing the on-line
      identification of most of the known constituents, i. e., flavonoids,
      anthraquinones and the typical dianthronic sennosides. However, the identity of
      four compounds could not be ascertained on-line under the given LC/MS conditions.
      These substances were isolated and their structures elucidated as kaempferol, the
      naphthalene derivative tinnevellin 8-glucoside and two new carboxylated
      benzophenone glucosides.

PMID- 11988862
TI  - HPLC analysis of plasma 9-methoxycanthin-6-one from Eurycoma longifolia and its
      application in a bioavailability/pharmacokinetic study.
AB  - A new and simple HPLC method using fluorescence detection was developed to
      determine 9-methoxycanthin-6-one, an active compound of Eurycoma longifolia Jack
      in rat and human plasma. The method entailed direct injection of plasma sample
      after deproteinization using acetonitrile. The mobile phase comprised
      acetonitrile and distilled water (55 : 45, v/v). Analysis was run at a flow rate
      of 1.0 ml/min with the detector operating at an excitation wavelength of 371 nm
      and emission wavelength of 504 nm. The method was specific and sensitive with a
      detection limit of 0.6 ng/ml and a quantification limit of approximately 1.6
      ng/ml. The method was applied in a pilot pharmacokinetic/bioavailability study of
      the compound in rats. Less than 1 % of the compound was found to be absorbed
      orally.

PMID- 11988863
TI  - Diphyllin acetylapioside, a 5-lipoxygenase inhibitor from Haplophyllum
      hispanicum.
AB  - The topical anti-inflammatory activity of Haplophyllum hispanicum Spach is due to
      the presence of arylnaphthalene-type lignans acting as 5-lipoxygenase (5-LOX)
      inhibitors. The effects of the methanolic extract of this species on cellular
      systems have been determined by HPLC-DAD analysis. Diphyllin acetylapioside
      proved to be the main lignan endowed with 5-LOX inhibitory activity.

PMID- 11988864
TI  - Antibacterial diterpenoids from Fabiana densa var. ramulosa.
AB  - A biologically monitored fractionation of the resinous exudate of Fabiana densa
      Remy var. ramulosa Wedd. led to the isolation of the two new diterpenes: ent
      beyer-15-en-18-O-succinate and ent-beyer-15-en-18-O-oxalate as the unique
      compounds responsible for the observed antibacterial activity of this extract.
      Their structures were determined by 1D and 2D NMR spectroscopy.

PMID- 11988865
TI  - Antifungal metabolite with a new carbon skeleton from Keissleriella sp. YS4108, a
      marine filamentous fungus.
AB  - In addition to four known metabolites (4-acetyl-6,8-dihydroxy-5
      methylisocoumarin, 6,8-dihydroxy-3-methylisocoumarin, 6,8-dihydroxy-3,5,7
      trimethylisocoumarin and 3,3'-oxy-(5-methyl)-phenol), bioassay-guided
      fractionation of the culture of Keissleriella sp., a marine filamentous fungus
      (strain number: YS 4108), afforded an antifungal metabolite with a new carbon
      skeleton whose structure was elucidated spectrometrically as 3,6,8-trihydroxy-3
      [3,5-dimethyl-2-oxo-3(E)-heptenyl]-2,3-dihydronaphthalen-1(4H)-one. In vitro
      antifungal assays of all isolates revealed that the new metabolite and 3,3'
      oxybis[5-methylphenol] were inhibitory to the growth of the human pathogenic
      fungi Candida albicans, Tricophyton rubrum and Aspergillus niger with MICs of the
      former being 40, 20 and 80 microg/ml, and those of the latter 10, 30 and 50
      microg/ml, respectively.

PMID- 11988866
TI  - Prevention of cellular ROS damage by isovitexin and related flavonoids.
AB  - The antioxidant properties of isovitexin and related flavonoids were studied.
      Isovitexin inhibited xanthine oxidase with an IC50 value of = 15.2 microM. The
      flavonoid analogues, apigenin, kaempferol, quercetin, myricetin, and genistein
      also inhibited xanthine oxidase with IC50 values of 0.58, 2.18, 1.09, 9.90, and
      4.83 microM, respectively. Isovitexin protected DNA from the Fenton reaction
      induced breakage in a dose-dependent manner with an IC50 value of 9.52 microM.
      Isovitexin also protected HL-60 cells from the ROS damage induced by the
      xanthine/xanthine oxidase reaction. Isovitexin exhibited the lowest cytotoxicity
      toward HL-60 cells (LD50 >400 microM) compared to the other flavonoids examined.
      In addition, excess hydrogen peroxide induced by cadmium in A2780 ovarian cells
      was significantly suppressed by isovitexin. These results suggest that isovitexin
      in rice may protect cells from oxidative stress.

PMID- 11988867
TI  - Inhibition of vascular endothelial growth factor expression and production by
      triptolide.
AB  - Triptolide, the major component of the diterpenoids of the Chinese herb
      Tripterygium wilfordii Hook f. (Celastraceae), inhibited vascular endothelial
      growth factor expression and secretion in endothelial cells treated by 12-O
      tetradecanoylphorbol 13-acetate dose-dependently. This effect may be one of the
      mechanisms underlying the therapeutic effects of triptolide on rheumatoid
      arthritis.

PMID- 11988868
TI  - Induction of differentiation in human hepatocarcinoma cells by isoverbascoside.
AB  - Isoverbascoside, a phenylethanoid glycoside, was isolated from Chinese folk
      medicine herb Pedicularis striata Pall. Here we report that isoverbascoside is
      capable of inducing differentiation in human hepatocellular carcinoma (HCC) cell
      line SMMC-7721. When treated with isoverbascoside, the proliferation of SMMC-7721
      cells was markedly inhibited in a dose- and time-dependent manner, and the
      average cell population doubling time was delayed. Exposure of cells to 20
      micromol/l isoverbascoside led to the decline of colony formation efficiency on
      soft agar, induced G0/G1 arresting, and resulted in the decrease of gamma
      glutamyltransferase (gamma-GT) activity and the increase of tyrosine
      aminotransferase (TAT) activity, two marker enzymes, respectively, representing
      HCC malignance and differentiation stage. These results suggest that
      isoverbascoside possess the activity of inducing differentiation in SMMC-7721
      cells.

PMID- 11988869
TI  - Bergenin is the antiarrhythmic principle of Fluggea virosa.
AB  - Bergenin was isolated from the aerial parts of Fluggea virosa (Euphorbiaceae).
      Its structure was elucidated on the basis of chemical and spectral data. Anti
      arrhythmic effects of bergenin were investigated. At concentrations of 0.2 mg/kg,
      0.4 mg/kg, and 0.8 mg/kg, bergenin showed distinct therapeutic effects on BaCl2
      induced arrhythmias in rats. At concentrations of 0.4 mg/kg and 0.8 mg/kg
      bergenin significantly countered arrhythmias induced by ligation and reperfusion
      of the coronary artery. At 0.8 mg/kg, bergenin elevated the atria fibrillation
      threshold in rabbits from 1.34 mV to 1.92 mV. Our results suggest that bergenin
      has good potential to treat cardiac arrhythmias.

PMID- 11988870
TI  - Shogaols from Zingiber officinale protect IMR32 human neuroblastoma and normal
      human umbilical vein endothelial cells from beta-amyloid(25-35) insult.
AB  - From the rhizome of Zingiber officinale L. (Zingiberaceae), four shogaols that
      protect IMR32 human neuroblastoma and normal human umbilical vein endothelial
      cells from beta-amyloid(25 - 35) insult at EC50 = 4.5 - 81 microM were isolated.
      The efficacy of cell protection from beta-amyloid(25 - 35) insult by these
      shogaols was shown to improve as the length of the side chain increases.

PMID- 11988871
TI  - Constituents of Burasaia madagascarensis: a new clerodane-type diterpene.
AB  - From an ethanol extract of the stems of Burasaia madagascarensis Thouars
      (Menispermaceae) were isolated N-acetylnornuciferine and two clerodane-type
      diterpenes, one of them, epicordatine, being new. The structures were established
      by the interpretation of the spectral data. All the described compounds exhibited
      weak antimalarial activity.

PMID- 11988872
TI  - Two new alkaloids of the crinane series from Pancratium sickenbergeri.
AB  - Two new alkaloids; ent-6alpha/6beta-hydroxybuphanisine, (-)-8-demethylmaritidine
      and seven known alkaloids were isolated from Pancratium sickenbergeri grown in
      Egypt. Three of the known alkaloids were tested in the NCI cytotoxicity screen,
      but were found to be inactive.

PMID- 11988873
TI  - High performance liquid chromatography analysis of canthinone alkaloids from
      Eurycoma longifolia.
AB  - A reversed phase-high performance liquid chromatography method with a photodiode
      array detector was developed for the simultaneous determination of three major
      alkaloids, 9-methoxycanthin-6-one (1), 3-methylcanthin-5,6-dione (2) and its 9
      methoxy analogue (3) in Eurycoma longifolia Jack. These alkaloids were easily
      separated by a gradient elution protocol of 20 - 42 % acetonitrile in 0.1 %
      acetic acid. Compound 1 showed characteristic absorption at 350 nm only whereas
      its dione analogues, 2 and 3 displayed strong absorptions at both 350 and 451 nm.
      The linear calibration ranges were 0.7 - 50 microg x mL(-1) for 1, 1.5-50 microg
      x mL(-1) for 2 and 3.1 -100 microg x mL(-1) for 3. The recoveries of the three
      alkaloids were 90.8-101.0% with relative standard deviations from 0.35 to 6.31 %
      (n = 3). The limits of detection for all the alkaloids were within the range of
      0.35 - 0.7 microg x mL(-1). This method was successfully applied to the
      phytochemical analysis of E. longifolia roots obtained from different sources.

PMID- 11988874
TI  - Introduction.

PMID- 11988875
TI  - Select findings and conclusions.

PMID- 11988876
TI  - Policy recommendations.

PMID- 11988877
TI  - Emergence, spread, and environmental effect of antimicrobial resistance: how use
      of an antimicrobial anywhere can increase resistance to any antimicrobial
      anywhere else.
AB  - Use of an antimicrobial agent selects for overgrowth of a bacterial strain that
      has a gene expressing resistance to the agent. It also selects for the assembly
      and evolution of complex genetic vectors encoding, expressing, linking, and
      spreading that and other resistance genes. Once evolved, a competitive construct
      of such genetic elements may spread widely through the world's bacterial
      populations. A bacterial isolate at any place may thus be resistant-not only
      because nearby use of antimicrobials had amplified such a genetic construct
      locally, but also because distant use had caused the construct or its components
      to evolve in the first place and spread there. The levels of resistance at any
      time and place may therefore reflect in part the total number of bacteria in the
      world exposed to antimicrobials up until then. Tracing the evolution and spread
      of such genetic elements through bacterial populations far from one another, such
      as those of animals and humans, can be facilitated by newer genetic methods.

PMID- 11988878
TI  - Generally overlooked fundamentals of bacterial genetics and ecology.
AB  - Several important aspects of the antimicrobial resistance problem have not been
      treated extensively in previous monographs on this subject. This section very
      briefly updates information on these topics and suggests how this information is
      of value in assessing the contributions of human and agricultural use of
      antimicrobial agents on the problem of increasing antimicrobial resistance. The
      overall themes are (1) that propagation of resistance is an ecological problem,
      and thus (2) that ameliorating this problem requires recognition of long
      established information on the commensal microbiota of mammals, as well as that
      of recent molecular understanding of the genetic agents involved in the movement
      of resistance genes.

PMID- 11988879
TI  - Antimicrobial use and resistance in animals.
AB  - Food animals in the United States are often exposed to antimicrobials to treat
      and prevent infectious disease or to promote growth. Many of these antimicrobials
      are identical to or closely resemble drugs used in humans. Precise figures for
      the quantity of antimicrobials used in animals are not publicly available in the
      United States, and estimates vary widely. Antimicrobial resistance has emerged in
      zoonotic enteropathogens (e.g., Salmonella spp., Campylobacter spp.), commensal
      bacteria (e.g., Escherichia coli, enterococci), and bacterial pathogens of
      animals (e.g., Pasteurella, Actinobacillus spp.), but the prevalence of
      resistance varies. Antimicrobial resistance emerges from the use of
      antimicrobials in animals and the subsequent transfer of resistance genes and
      bacteria among animals and animal products and the environment. To slow the
      development of resistance, some countries have restricted antimicrobial use in
      feed, and some groups advocate similar measures in the United States.
      Alternatives to growth-promoting and prophylactic uses of antimicrobials in
      agriculture include improved management practices, wider use of vaccines, and
      introduction of probiotics. Monitoring programs, prudent use guidelines, and
      educational campaigns provide approaches to minimize the further development of
      antimicrobial resistance.

PMID- 11988880
TI  - Uses of antimicrobials in plant agriculture.
AB  - Bacterial diseases of plants are less prevalent than diseases caused by fungi and
      viruses. Antimicrobials for prophylactic treatment of bacterial diseases of
      plants are limited in availability, use, and efficacy, and therapeutic use is
      largely ineffective. Most applications are by spray treatments in orchards.
      Monitoring and surveillance for drug resistance are not routinely done. In the
      United States, data on use of antimicrobials for treatment of bacterial diseases
      of plants are limited to streptomycin and oxytetracycline. Resistance to
      streptomycin has become widespread among bacterial phytopathogens; no resistance
      among these bacteria has yet been reported for oxytetracycline. No human health
      effects have been documented since inception of use of antimicrobials in plants
      in the 1950s. Transfer of antimicrobial resistance from marker genes in
      transgenic plants to bacteria has not been documented under natural conditions in
      field-grown plants. However, antimicrobial-resistance genes are being eliminated
      from use as marker genes because of concerns about possible transfer from plant
      genomes back to bacteria, with further horizontal transfer to the bacteria in the
      environment, or from plant genomes to animals by plant consumption. No new
      antimicrobials are expected to be used in plant agriculture because of high costs
      of development, regulatory constraints, and environmental and human health
      concerns. Alternatives to antimicrobials, such as biocontrol agents, transgenic
      plants, and novel chemicals, are being developed and marketed, although their
      efficacy remains to be determined.

PMID- 11988881
TI  - Human diseases caused by foodborne pathogens of animal origin.
AB  - Many lines of evidence link antimicrobial-resistant human infections to foodborne
      pathogens of animal origin. Types of evidence reviewed include: (1) direct
      epidemiologic studies; (2) temporal evidence; (3) additional circumstantial
      evidence; (4) trends in antimicrobial resistance among Salmonella isolates; and
      (5) trends in antimicrobial resistance among other pathogens, such as
      Campylobacter jejuni. Commensal microorganisms in animals and humans may
      contribute to antimicrobial resistance among pathogens that cause disease among
      humans. For instance, enterococci of food-animal origin, particularly strains
      that are vancomycin resistant, have been linked to strains found in the human
      gastrointestinal tract. The latent period between the introduction of a given
      antimicrobial and emergence of resistance varies considerably, but once the
      prevalence in a population reaches a certain level, control becomes extremely
      difficult.

PMID- 11988882
TI  - Potential mechanisms of increased disease in humans from antimicrobial resistance
      in food animals.
AB  - There are at least 5 potential mechanisms by which antimicrobial resistance can
      have adverse effects on human health. The first, called the "attributable
      fraction," relates to individuals who become infected only because they are
      taking an antimicrobial agent (for unrelated reasons) to which the pathogen is
      resistant: the antimicrobial agent, by suppressing their normal microbiota,
      renders them more vulnerable to infection. A second mechanism involves the
      linkage of virulence traits to resistance traits so that resistant organisms may
      be more virulent than susceptible organisms. A third mechanism is that treatment
      may be rendered ineffective by the choice of a drug to which the pathogens are
      resistant or may be complicated by the need to use an agent with less desirable
      attributes than would otherwise be the case. A fourth mechanism is the animal
      equivalent of the attributable fraction: resistant pathogens acquired by this
      mechanism in food animals may then be transmitted through the food chain to
      humans. Last, resistance traits can be acquired by the commensal flora of
      animals; from this reservoir, resistance traits could find their way through the
      food chain to commensals and pathogens of humans.

PMID- 11988883
TI  - Excess infections due to antimicrobial resistance: the "Attributable Fraction".
AB  - Antimicrobial use causes a transient decrease in an individual's resistance to
      colonization by noncommensal bacteria ("competitive effect") and increases the
      likelihood of infection upon exposure to a foodborne pathogen. The additional
      "selective effect" of antimicrobial resistance results in a >3-fold increase in
      vulnerability to infection by an antimicrobial-resistant pathogen among
      individuals receiving antimicrobial therapy for unrelated reasons. Combining the
      increase in vulnerability to infection with the prevalence of taking an
      antimicrobial agent, it is possible to estimate the attributable fraction, or the
      number of excess infections that occurred as a result of the unrelated use of an
      antimicrobial agent to which the pathogen was resistant. Calculations based on
      estimates of the annual infection rates and attributable fractions of infections
      with nontyphoidal Salmonella and Campylobacter jejuni suggest that resistance to
      antimicrobial agents results annually in an additional 29,379 nontyphoidal
      Salmonella infections, leading to 342 hospitalizations and 12 deaths, and an
      additional 17,668 C. jejuni infections, leading to 95 hospitalizations.

PMID- 11988884
TI  - Morbidity of infections caused by antimicrobial-resistant bacteria.
AB  - Antimicrobial resistance can have 2 effects on the outcome of infection: there
      can be an accompanying change in the virulence of the organism, and there can be
      a poorer response to treatment because of the empiric choice of an antimicrobial
      to which the organism is resistant. We have reviewed published studies relating
      antimicrobial resistance to the outcomes of infection caused by enteric
      pathogens. The data for Salmonella and Campylobacter infections suggest that
      antimicrobial-resistant strains are somewhat more virulent than susceptible
      strains-that is, they cause more prolonged or more severe illness than do
      antimicrobial-susceptible strains. However, not all studies corrected for
      possible differences in age and underlying diseases between patients infected by
      antimicrobial-resistant and -susceptible strains of Salmonella. Two studies of
      Campylobacter infection suggest that poorer outcomes with antimicrobial-resistant
      pathogens could be related to the initial choice of an ineffective antimicrobial
      for treatment. Estimates from various sources indicate that fluoroquinolone
      resistance, likely acquired from the administration of antimicrobials to food
      animals, leads to >400,000 excess days of diarrhea in the United States per year
      compared with the duration that would occur if all of the isolates were
      susceptible. Antimicrobial resistance also could account for an extra 8677 days
      of hospitalization for nontyphoidal salmonellosis, mainly arising from food
      animals.

PMID- 11988885
TI  - Review of assessments of the human health risk associated with the use of
      antimicrobial agents in agriculture.
AB  - To our knowledge, no comprehensive risk assessment of agricultural uses of
      antimicrobial agents has been published. The published risk assessments of
      antimicrobial use in farm settings are all subject to multiple, serious
      limitations in scope, including (1) limitation to one species of microorganism;
      (2) limitation to one or a very few related antimicrobial agents; (3) limitation
      to a single outcome (death, hospital days, number of illnesses, etc.); (4)
      limitation to one species of farm animal (e.g., chicken or swine); and (5)
      limitation to therapeutic use, despite reason for concern about misstated, off
      label, or illegal use. In addition, all of the risk assessments reviewed
      overlooked important issues by accepting 2 further limitations: (6) limiting the
      scope of the analysis to what has already happened and ignoring the effects of
      continuing the practices of recent years; and (7) examining only the effects on
      the species of microorganism that was initially affected and ignoring the cross
      species spread of resistance by plasmid transfer. After our review of the risk
      assessments now available, we propose a comprehensive scheme for organizing
      existing knowledge and dealing with critical gaps.

PMID- 11988886
TI  - [Clinical treatment (non surgical) of spasticity in cerebral palsy].
AB  - OBJECTIVE: A review about the procedures used in the non surgical management of
      spasticity in children with cerebral palsy. DEVELOPMENT: Therapeutic modalities
      for the management of spasticity in cerebral palsy include: (1) elimination of
      factors aggravating spasticity: pain, fatigue, stress, excitement, cold, illness,
      sleep disturbance, immobility, and hormonal changes; (2) rehabilitative
      therapies, there are four major groups: (a) biomechanical approach, (b)
      neurophysiologic approach, (c) developmental approach and (d) sensory approach;
      (3) orthosis; (4) oral pharmacotherapy: baclofen, tizanidine, diacepam and
      dantroleno; (5) chemical denervation: phenol injections and botulinum toxin
      injections. The medical management of spasticity in cerebral palsy is based on:
      1. Oral pharmacotherapy: (a) baclofen, binds GABAB receptors of spinal
      interneurons presynaptically, inhibits release of excitatory neurotransmitters in
      the spinal cord; (b) tizanidine, binds alfa 2 adrenergic receptors
      presinaptically, inhibits release of excitatory neurotransmitters in the spinal
      cord; (c) diacepam, augments GABA mediated inhibition in the spinal cord and
      supraspinally;(d) dantrolene, inhibits release of calcium from sarcoplasmic
      reticulum in muscle, weakens muscle contraction in response to myofiber
      excitation. 2. Chemical denervation: (a) phenol injection perineurally or into
      the motor point disrupts efferent signals from hyperexcitable anterior horn cells
      causing necrosis of axons or muscle; (b) botulinum toxin injection in selected
      muscles blocks the release of acetylcholine presynaptically and weakens the force
      of muscle contraction produced by hyperexcitable motoneurons. CONCLUSIONS: At the
      present time, there is not irrefutable evidence of a sustain benefit of physical
      rehabilitation in the management of spasticity. There are few studies with oral
      pharmacological agents involving children with cerebral palsy to define its role.
      On the other hand, botulinum toxin A is effective, well tolerated, and safe in
      the treatment of spasticity in children with cerebral palsy.

PMID- 11988887
TI  - [Benign focal epilepsies in infancy, childhood and adolescence].
AB  - INTRODUCTION. The last proposal for a classification of epileptic seizures and
      syndromes of the International League Against Epilepsy (ILAE) includes
      recognition of several groups of epileptic syndromes and among them one of
      idiopathic focal epilepsies of infancy and childhood, and another of familial
      (autosomal dominant) focal epilepsies. The syndromes here described belong to
      these two groups and are: benign familial infantile seizures, benign infantile
      seizures (nonfamilial), benign childhood epilepsy with centrotemporal spikes
      (BCECTS), idiopathic occipital epilepsy of childhood Gastaut type (IOEC) and
      benign occipital epilepsy of childhood Panayiotopoulos type (BOEC). Atypical
      evolutions of the cases with BCECTS, IOEC and BOEC diagnosed and followed in our
      group are described, showing that these conditions are not always so benign.
      Finally, the so called benign focal convulsions of adolescence are considered,
      even when they were not included in ILAE s last proposal.

PMID- 11988888
TI  - [Non specific leukodystrophy. A new case of vacuolizing leukoencephalopathy with
      megalencephaly].
AB  - INTRODUCTION: Amongst the conditions affecting the white matter, the disorders of
      myelinization, including the leukodystrophies, are important in the field of
      paediatric neurology. Although classically they have been classified according to
      whether the metabolic defect was known or not, at the present time great advances
      in neuroimaging have clarified many genetic disorders involving the white matter
      and new classifications have been devised. The group of unknown aetiology
      includes the so called non specific leukodystrophies, characterized by their
      onset in infancy with a usually more moderate clinical course, and neuro imaging
      (computerized tomography CT magnetic resonance MR ) with alteration of the signal
      from the white matter which is symmetrical, bilateral and diffuse. Study and
      investigation of the patterns of MR has permitted isolation of two new clinical
      conditions of the non specific leukodystrophies group: leukodystrophy with
      megalencephaly and temporal cysts (Van der Knaap, 1995) for which currently the
      term vacuolizing leukoencephalopathy with megalencephaly is preferred and the
      CASH syndrome (childhood ataxia with central hypomyelinization or vanishing white
      matter disease) (Van der Knaap, 1997). DEVELOPMENT: We present a review of nine
      cases of non specific leukodystrophies with an average course of 13 years. They
      were studied using the protocol of the European working party on demyelinating
      diseases. One of these fulfilled clinical and radiological criteria for the
      diagnosis of vacuolizing leukoencephalopathy with megalencephayl: onset in early
      childhood, macrocephaly, normal metabolic studies, moderate progression and
      alteration of the white matter signal which was bilateral, symmetrical and
      diffuse with the presence of oedema and temporal subcortical cysts. We discuss
      the most relevant articles currently published on this condition.

PMID- 11988889
TI  - [New techniques used to monitor cerebral function in the newborn].
AB  - INTRODUCTION: Continuous display four channels EEG monitoring and near infrared
      spectroscopy (NIRS) are relatively new and valuable techniques used for
      continuous brain monitoring in the neonatal period. Supporting the value of
      continuous display four channels EEG monitoring in the evaluation of neonates
      with paroxysmal motor events is a study recently conducted at Miami Children s
      Hospital. DEVELOPMENT: In this study 30 events were captures in 88 hours of
      simultaneous continuous display four channels EEG monitoring and continuous video
      EEG telemetry recording in five patients. Fourteen of the events were consider
      epileptic and 16 were considered non epileptic after evaluation of the continuous
      display four channels EEG monitoring printed epochs. RESULTS: The continuous
      video EEG telemetry confirmed the diagnosis for all the events. Several studies
      attest to the usefulness of NIRS in neonates and in older children with
      pathologies similar to those seeing in neonates. CONCLUSIONS: 1. NIRS is the best
      method to monitor regional cerebral oxygen saturation; 2. Regional cerebral
      oxygen saturation values are primarily those of the venous circulation in the
      subcortical white matter below the sensor; 3. Values of regional oxygen
      saturation should be considered not independently but only relative as a change
      over time; 4. Decreased regional cerebral oxygen saturation may be a sign of
      impending or established hypoxemia or hypotension, increased cerebral metabolic
      demands, or a cerebral oxygenation or perfusion problem that involve only brain,
      and 5. NIRS should be used in conjunction with arterial oxygen saturation and
      pressure monitoring (to detect hypoxemia and hypotension), with EEG to detect
      increased cerebral metabolic demands (electroencephalographic seizures) and with
      anterior cerebral artery Doppler ultrasound to detect perfusion (decreased flow
      velocity) and oxygenation (constant flow velocity) problems that involve only the
      brain.

PMID- 11988890
TI  - [Disorders of the nervous system and alteration of the fundus oculi].
AB  - OBJECTIVE: To show the neurological disorders associated with ocular changes
      mainly affecting retina and which can be seen during the first year of age.
      DEVELOPMENT: It is used the personal experience and the reported papers of the
      literature related with the subject to make a short review of the main
      neurological, biochemical, radiological and genetical alterations as well as the
      peculiarities of the lesions that we can see by the ocular fundus exploration,
      and we try to show through images the retinal alterations associated with the
      neurological diseases of very young children. CONCLUSION: The retinal alterations
      that we can see by ocular fundus exploration can lead us to an early neurological
      diagnosis.

PMID- 11988891
TI  - [Neonatal myasthenic syndromes].
AB  - INTRODUCTION: In the newborn, myasthenia can present either as transient neonatal
      myasthenia or as a congenital syndrome. At present at least 8 syndromes involving
      neonatal neuromuscular junction (NMJ) malfunction have been described; one caused
      by the passage of transplacental antibodies from mother to child, while all but
      one of the rest are inherited. Inheritance in all but two syndromes is autosomal
      recessive. One is an autosomal dominantly inherited illness; in another the mode
      of inheritance is not clear. The deficit in function of the NMJ is presynaptic in
      3 instances, at the junctional gap in 1, and postsynaptic in at least 3 other
      syndromes. DEVELOPMENT: We will review the clinical symptoms, as well as
      neurophysiologic and genetic testing available for diagnosis. We explain how, at
      least, in some of the syndromes, one can begin appropriate therapy based on
      clinical, neurophysiological and simple pharmacological testing. CONCLUSION:
      However, in many cases, it becomes necessary to refer the patient or a tissue
      sample, usually an intercostal nerve muscle preparation, to one of the very few
      centers in the world where in vitro neurophysiologic, microstructural and genetic
      procedures leading to a more precise diagnosis can be performed.

PMID- 11988892
TI  - [Treatment of spasticity in cerebral palsy with botulinum toxin].
AB  - OBJECTIVE: A review of the pathophysiological and developmental basis,
      measurement scales and the usefulness of botulinum toxin A injections in selected
      muscles for the treatment of spasticity in children with cerebral palsy.
      DEVELOPMENT: Cerebral palsy is the most common cause of spasticity in children.
      The increase in muscle length is achieved through the addition of sarcomeres in
      series at the level of the muscle tendinous junction. The regulation of the
      number of sarcomeres seems to be determined by the lengthening of the muscle. The
      muscle contracture is a shortening of the length of a muscle as a result of a
      decrease in the number of sarcomeres. Spasticity and motor function assessment
      scales used in children with cerebral palsy: a) Modified Ashworth scale for the
      assessment of spasticity; b) modified Tardieu scale for the assessment of dynamic
      muscle length; c) muscle spasms frequency scale; d) modified Medical Research
      Council scale for muscle strength; e) hip adductor muscle tone scale; f) global
      pain scale with affective facial expression represented in a drawing; g)
      goniometric measurement of the joint range of movement; h) Palisano gross motor
      function measure; i) observational video gait analysis scale. Recommended
      guidelines for dosing the botulinum toxin A: 1. Total maximum dose administered
      per visit up to 15 U/kg or a total of 400 U; 2. Dose range of large muscles 3 to
      6 U/kg per visit; 3. Dose range of small muscles 1 to 3 U/kg per visit; 4.
      Maximum dose per injection site: 50 U dividing the total planned unit dose/muscle
      into equal amounts/injection site; 5. Frequency: no more than one injection every
      3 months, frequently once every 6 or more months. CONCLUSION: Botulinum toxin A
      injection is a well tolerated, safe and effective procedure in the treatment of
      children with spastic cerebral palsy.

PMID- 11988894
TI  - [Morphological study of brainstem auditory evoked potentials. The effect of the
      position of the reference electrode].
AB  - INTRODUCTION: In view of the discrepancy between the siting of electrodes and the
      effects on BAEP, we made a morphological study of 30 healthy volunteers, 15 men
      and 15 women. DEVELOPMENT: In each person we obtained the BAEP with the active
      electrode on the ear lobe ipsilateral to the stimulated ear and the reference ear
      successively at four different sites: vertex (Cz), high frontal (Fz), earlobe
      contralateral to the stimulated ear and the spinous process of the seventh
      cervical vertebra (CV7). The I, III and V waves were present in all cases and
      tests, followed in frequency by II, IV and VII. In Cz and Fz the first five
      deflections were almost always seen, and these are the most useful for
      neurodiagnosis. The waves of greatest amplitude were 1 in both sexes in the ear
      lobe and CV7 for Fz and Cz in men and V for women. Regarding the complex
      morphological variants, the greatest incidence in the III IV V complex was
      observed in Fz in both sexes. In CV7 there was a greater range of variants, as
      found by other workers, but with greater morphological separation of waves IV and
      V. They were infrequent in waves I II and VI VII and least common in Fz and Cz.
      CONCLUSION: We consider that the BAEP obtained with reference to Cz and Fz are
      ideal for interpretation, since there is greater constancy, global amplitude and
      morphological clarity of the first five deflections and less morphological
      complexity of the other waves.

PMID- 11988895
TI  - [Pseudoathetosis after medullar and pontine hemorrhage].
AB  - INTRODUCTION: Athetosis is a slow and purposeless involuntary movement which
      changes in frequency, severity. The term pseudoathetosis is used when this
      movement is associated with proprioceptive sensory impairment. CLINICAL CASE: A
      63 year old man developed right medulla and pons hemorrhage and presented loss of
      proprioception in left hemibody and athetosis movements in left hand. CONCLUSION:
      We report a case of pseudoathetosis associated with loss of proprioceptive
      sensation.

PMID- 11988896
TI  - [Neuregulins: A family of factors with critical functions during nervous system
      development and in the cellular transformation and differentiation].
AB  - INTRODUCTION: The neuregulins are a family of factors that perform important
      functions during the development of the nervous system, neuromuscular junction
      and heart. These factors are also involved in nervous system disorders, and in
      the generation and progression of tumors. DEVELOPMENT: There are four genes and
      many isoforms which share a similar molecular structure. The neuregulins are
      differentially expressed and bind with different affinities to specific
      combinations of ErbB receptors. This level of complexity is directing numerous
      researching in order to understand the molecular mechanisms that regulate a
      specific pathway. CONCLUSION: Neuregulin ErbB receptor complexes activate
      specific intracellular pathways that culminate in very different fates:
      differentiation or proliferation.

PMID- 11988897
TI  - [Subdural haematoma and subarachnoid cyst].

PMID- 11988898
TI  - [Fukuyama type congenital muscular dystrophy].

PMID- 11988899
TI  - [Treatment of intracranial aneurysms].

PMID- 11988901
TI  - [Efficacy and tolerability of long term topiramate in drug resistant epilepsy in
      adults].
AB  - OBJECTIVE: With the objective of evaluating the efficacy and tolerability of
      topiramate (TPM) in resistant epilepsy, we did a retrospective, open,
      multicentric analysis of 56 patients aged over 15 years in whom TPM was given as
      the second, third or fourth drug. All patients had already been on treatment for
      at least 18 months when topiramate was started. The average follow up was 27.2
      months. RESULTS: At the close of the study 16% of the patients were asymptomatic,
      23% had a 75% reduction in seizures and 36% a 50% reduction. The drug was
      withdrawn in 25% of the cases. The adverse effects noted were: nephrolithiasis,
      asthenia, loss of hair, diarrhoea, weight loss of over 5kg., agitation,
      aggressiveness, language disorders, ataxia, tremor, somnolence and confusion. The
      drug had to be suspended when these adverse effects affected the central nervous
      system moderately or severely, and when there were general effects such as renal
      calculi in one case and weight loss associated with symptoms which worried the
      patients in two cases. CONCLUSIONS: Thus, TPM is an effective drug in refractory
      epilepsy and most patients continue on this treatment. The side effects are
      typical of the drug, and although there is no risk to life, the patient should be
      warned of them.

PMID- 11988902
TI  - [Pure lower motoneurone syndrome in a series of six patients].
AB  - INTRODUCTION: Lower motoneurone syndromes (SMNI) have been defined by their
      clinical pattern, anomalies in nerve conduction and the presence of
      antiglycolipid antibodies. The possible response to immunotherapy is another
      characteristic which makes these syndromes interesting. PATIENTS AND METHODS: We
      studied the clinical and electrophysiological data, clinical progress and
      response to treatment of a series of six patients, with a pure lower motoneurone
      syndrome, with a follow up period of between 5 and 13 years. CONCLUSIONS: The
      clinical phenotype of our patients was: male, middle aged, the clinical
      topography showed only lower motoneurone involvement, predominantly or
      exclusively limited to the upper limbs, asymmetrical, distal rather than
      proximal, with a chronic course progressing initially but later becoming stable.
      From the electrophysiological point of view some of our cases were of SMNI. In
      these the conduction block was not permanent although there were signs of axon
      loss and multifocal demyelination. Response to treatment with intravenous
      immunoglobulins was seen in patients with anti GMI antibodies of IgM type and
      recent signs of clinical deterioration, whether there were conduction blocks
      present or not. In the cases which responded to this treatment there was
      tolerance and dependence following repeated transfusions of IV IgG.

PMID- 11988903
TI  - [Somatomorphic and factitious disorders. Our experience in a regional reference
      neuropaediatric department].
AB  - INTRODUCTION AND OBJECTIVES: Children often consult for fictional or very
      exaggerated symptoms, grouped together as factitious disorders (TF), disorders
      due to somatomorphic pain (TDS), disorders due to somatization (TS) and
      conversion disorders (TC). Patients and method. We studied cases of TF, TDS, TS
      and TC evaluated by the neuropaediatric department of the Hospital Miguel Servet
      de Zaragoza between May 1990 and August 2001. RESULTS: There were 134 children
      identified as having TF TDS TS TC: There were 91 girls (67.9%) and 43 boys
      (32.1%). They made up 2.47% of the 5,417 children included in the neuropaediatric
      data base. The mean age was 10 years and 9 months, ranging between 3 and 16 years
      with only 9 children aged under 7 years. The commonest syndromes were: paroxystic
      disorders, headache, other pain, paraesthesia, hypovision, and other visual
      alterations, paresias, tremors and other disorders of movement, disorders of
      gait, lack of air, hyperventilation and dysphagia. There was often more than one
      motive for consultation, with sometimes more than four. The commonest
      complementary tests done were: EEG, fundus oculi, cranial CAT scan, CPK, EMG/ENG,
      cranial MR, spinal MR, CSF and osseous gammography. No further studies were made
      of 12 children (9%). CONCLUSIONS: The TF TDS TS TC are a common cause of
      assessment in neuropaediatric practice. It should be suspected in cases of
      multiple symptoms in children aged over 6 years, usually in girls. It is often
      necessary to carry out various complementary tests to rule out organic disorders.

PMID- 11988904
TI  - [Anhidrosis and hyperthermia associated with treatment with topiramate].
AB  - INTRODUCTION: It has been observed that if topiramate (TPM) is given together
      with other antiepileptic drugs when the temperature of the environment is high, a
      disorder involving sweating and thermo regulation may be seen as a side effect.
      PATIENTS AND METHODS: We describe ten patients, of an average age of 7 years and
      8 months, with refractory epileptic seizures. All were treated with topiramate,
      associated with the antiepileptic drugs they had been taking previously. During
      the summer months, when the environmental temperature was over 37  C, they had
      slight hyperthermia, hypohydrosis or more usually anhydrosis, red faces and
      tiredness which was markedly worse on effort. In one case there was also
      retention of urine and four others had known side effects. In seven patients the
      symptoms disappeared when the dose of TPM was reduced or the environment became
      cooler. In the other three cases TPM was withdrawn, due to the severe adverse
      effects seen in two cases and for being ineffective as treatment in the other
      cases. CONCLUSIONS: It is considered that in predisposed children, TPM causes
      autonomic dysfunction, probably of central origin, which is seen as a disorder of
      sweating and thermoregulation. Although the mechanism of this disorder is not
      known, since it occurs when the temperature is over 37  C, it would seem that it
      is due to a reduction in carbonic anhydrase isoenzymes II and IV. We suggest that
      it would be useful to establish a method to predict the patients at risk in
      summer, in hot regions, at the first sign of fatigability.

PMID- 11988905
TI  - [Lafora disease. A new case of confirmation of diagnosis on molecular genetic
      studies].
AB  - INTRODUCTION: Lafora s disease is a type of progressive myoclonic epilepsy with
      bad prognosis. Until now diagnosis was based on finding characteristic
      intracytoplasmatic polyglucosan bodies in biopsies of sweat secreting cells in
      the skin. Recently the gene responsible has been discovered. This permits firm
      diagnosis and screening of carriers. We present the case of a child diagnosed on
      molecular genetic studies. CLINICAL CASE: A 12 year old boy with a clinical
      history of three febrile seizures at the age of one year but no other
      abnormalities, presented a seizure of visual disorder with secondary
      generalization. There was no family history of seizures. Following a period of
      normality he had further seizures (clonic, visual and generalized myoclonic). The
      EEG showed generalized spike and wave activity, which was more marked after
      stimulation by light and became progressively worse. Neuroimaging studies were
      normal. In spite of treatment there was a progressive increase in visual and
      generalized myoclonic seizures together with deterioration of cognitive function
      and ataxia. Histological studies of the sweat glands showed homogeneous nodular
      deposits of intracytoplasmatic PAS+. Molecular studies of the EPM2A gene linked
      to chromosome 6q24 showed the presence of two mutations on the 1 and 4 exons.
      CONCLUSIONS: We describe a 12 year old patient with all the clinical features of
      Lafora type progressive myoclonic epilepsy in whom characteristic cytoplasmic
      bodies were found in the sweat gland biopsy. Molecular genetic studies of the
      EPM2A gene confirmed diagnosis of the disorder.

PMID- 11988906
TI  - [The thalamus: a dynamic door to perception].
AB  - y dependent on the activity of our senses for our relationship with the outside
      world, we may consider the thalamus to be a key part of perception. DEVELOPMENT.
      Far from behaving as a simple relay station, the thalamic circuits represent the
      framework on which to build a truly dynamic biological filter which can select
      the messages to reach the cortex according to their relevance and the behavioural
      state of the person. Such filtering implies the participation of many
      neurotransmitters which represent as many different systems. Outstanding amongst
      these are the groups formed by acetylcholine and nitric oxide axons arising from
      the brainstem, and corticofugal fibers which are sent back from the cortex to the
      thalamus. CONCLUSIONS. In this paper we review the functional aspects of the
      thalamic control of information, particularly of the visual system, with
      reference to alterations derived from its malfunction.

PMID- 11988907
TI  - [Acute flaccid paralysis].
AB  - Acute flaccid paralysis, a common paediatric disorder, is fundamentally caused by
      disorders involving neuromuscular diseases of acute onset. It generally presents
      as an acute or extremely acute motor disorder which is progressive or extremely
      progressive. Successful management depends on a rapid, accurate differential
      diagnosis, based on the patient s history of muscular weakness.

PMID- 11988908
TI  - [Cerebrovascular disease in childhood and adolescence. Ischaemic cerebral
      accidents].
AB  - In recent years attention has been drawn to cerebrovascular disease in children
      and adolescents, since cases are now better detected and hence there has been an
      apparent increase in their incidence. The traditional risk factors of adult
      cerebrovascular disease are considered to be unimportant in children and
      adolescents. In these young patients there are many other more important risk
      factors, genetic, metabolic and infections, acting alone or in combination. The
      most important of these are cardiac disorders, prothrombotic states and vascular
      disorders. There are many imaging techniques available for the investigation of
      patients with ischaemic symptoms, which permit early diagnosis using non invasive
      methods. The newer perfusion diffusion MR techniques may play an important part
      in evaluation and treatment, especially in patients at risk. Most treatment
      currently available is symptomatic. However, interventionist neuroradiology may
      in future play an important part in treatment in this age group. Recent studies
      have shown that the prognosis is not as good as previously thought and half the
      patients have motor sequelas and a similar number require special schooling.

PMID- 11988909
TI  - [Epileptic channelopathies].
AB  - OBJECTIVE: At the present time the study of epileptogenesis is becoming
      increasingly interested in the function of ionic channels in which localization
      of new gene sites and mutations have been aetiopathogenically related to certain
      syndromes involving epilepsy. The pathology of these channels known as
      channelopathies is responsible for a certain number of conditions affecting the
      central nervous and neuromuscular systems. Its clinical expression is often
      paroxystic. The mutations cause inactivation of the channel, which depending on
      the degree, conditions the phenotype of the process. DEVELOPMENT: We studied the
      main epileptic channelopathies related to idiopathic epilepsy syndromes. To date
      it has been possible to codify four genes responsible for: benign familial
      neonatal convulsions, generalized epilepsy with febrile convulsions plus and
      frontal lobe nocturnal dominant autosomal epilepsy, together with other syndromes
      in which potentially related mutations have arisen. CONCLUSIONS: Ionic channels,
      both voltage and receptor dependent, are involved in the genesis of idiopathic
      epilepsy syndromes. Their importance is due to the contribution made to
      understanding epileptogenesis and the application of this in the investigation of
      drugs which act by modifying the initial cause of the seizure. Today it may be
      said that the idiopathic epilepsies, or at least some of them, make up a family
      of channelopathies.

PMID- 11988910
TI  - [Neuromuscular hereditary channelopathies: non-dystrophic myotonias,
      paramyotonias and periodic paralysis].
AB  - INTRODUCTION: The ionic channels are complex glycoprotein structures, which cross
      the lipidic cellular membrane and allow the passage of electrically charged ions
      from one side of it to the other, thanks to the electrochemical gradient. A
      channelopathy is a disorder due to anomalous function of the ionic channels.
      DEVELOPMENT: In this study we analyze particularly the hereditary channelopathies
      with neuromuscular involvement non dystrophic myotonia, paramyotonias and
      periodic paralysis, and classify the clinical, physiopathological, molecular,
      genetic and therapeutic aspects. As far as possible we have divided the different
      conditions according to the channel involved, due to mutations which affect the
      sodium, calcium, chloride and potassium channels. We have also included
      neuromyotonic phenomena which are probably caused by channelopathies.
      CONCLUSIONS: Probably it will not be long before many of the conditions
      considered in this article have a better physiopathological explanation, more
      specific diagnostic procedures and a more rational approach to treatment.

PMID- 11988911
TI  - [Alternating hemiplegia in young babies].
AB  - INTRODUCTION. This paper review the state of the art of alternating hemiplegia of
      childhood. This entity is a rare neurologic disorder of infancy characterize by
      transient hemiplegic spells shifting from one side to another, and occasionally
      affecting to both hemispheres at the same time. Usually start before 18 months,
      many cases exhibit neonatal symptoms related with the disorder. Early
      symptomatology include abnormal ocular movements, mainly nystagmus, and tonic or
      dystonic attacks generally beginning before 6 months of age. These symptoms are
      frequently misdiagnosis as epilepsy. Typical hemiplegic fits which disappeared
      when infant felt asleep appeared by 12 months of age. Diagnosis is on clinical
      basis after excluding any other causes of fluctuating and transitory hemiplegic
      attacks. Complementary investigations, such as electroencephalograms, TAC, MRI,
      angiographic MRI, CFS are strictly normal. Cerebral SPECT show controversial
      abnormalities in some studies. We perform SPECT study in a alert 12 months old
      girl during an interictal period resulting in a non significant asymmetry, with
      lesser perfusion in left frontal basal and anterior temporal gyrus. Nevertheless,
      we observed an striking hyperperfusion in middle occipital area. Treatment is
      symptomatic with flunarizine. Our patient experience a dramatic decrease in
      frequency, duration and severity of hemiplegic attacks.

PMID- 11988912
TI  - [Disseminated acute encephalomyelitis in children].
AB  - INTRODUCTION: Disseminated acute encephalomyelitis (DAE) is an autoimmune
      inflammatory condition, usually monophasic with gradual resolution,
      polysymptomatic, usually in relation to a virus, bacteria or immunizations but
      may also occur in the absence of any obvious infection. OBJECTIVE: To describe
      DAE, its aetiology, clinical features, diagnosis and treatment. Also to analyze
      these aspects with regard to a series of 13 children with DAE. RESULTS: The
      clinical condition started with fever in 61% of the patients. The commonest
      neurological findings were sensory deterioration, convulsions and motor disorders
      (paresias). The cerebrospinal fluid was abnormal in four patients. MR showed
      hyperintense lesions of multifocal distribution, predominantly in the subcortical
      white matter. All patients were treated with intravenous methylprednisolone at a
      dose of 20 30 mg/kg. Clinical follow up showed complete recovery in 11/13
      patients and mild sequelae in two cases. CONCLUSIONS: Diagnosis of DAE is based
      on suggestive clinical data and MR findings. MR is very sensitive in detecting
      demyelinating lesions and is the method of choice for confirmation of the
      diagnosis. DAE is characterized by a satisfactory clinical course with
      simultaneous resolution of the demyelinating lesions.

PMID- 11988913
TI  - [Acute autoimmune polyradiculoneuropathies].
AB  - Landry Guillain Barr  Sthrol Syndrome (LGBS) is an acute autoimmune monophasic
      and selflimiting polyradiculoneuropathy affecting patients aged 19 to 59 years
      (1.7/100,000/year) more than below 18 year of age (0.8/100,000/year). Diagnostic
      criteria require: I. Progressive motor weakness of more than one limb, and II)
      absent muscle stretch reflexes. Features that strongly support the diagnosis are:
      1. Cease of progression of weakness by 4 weeks, relative symmetrical involvement
      of the limbs, presence of mild sensory symptoms or signs, involvement of cranial
      nerves VII (50%) more than IX, X, III, IV and VI, recovery within 2 to 3 weeks
      after progression stop, presence of autonomic dysfunction, and absent of fever at
      onset; 2. Cerebral spinal fluid elevation of protein after first week of symptoms
      and less than 10 mononuclear leukocytes/mm3 except HIV seropositive patients (<50
      cells/mm3), and 3. Nerve conduction slowing (<60% of normal ) or block at some
      point during the illness (80%), and increased distal motor latency up to 3 times
      above normal and F wave latency. There are four well defined clinical,
      pathological, neurophysiological and serological subtypes. Acute inflamatory
      demyelinating polyradiculoneuropathy (90%) and Miller Fisher syndrome (5%) are
      primarily demyelinating. Acute motor axonal neuropathy and acute motor sensory
      axonal neuropathy are primarily axonal (5%). Treatment includes supportive care
      and immunotherapy with high doses of intravenous IgG and plasmapheresis.

PMID- 11988914
TI  - [Juvenile dermatomyositis].
AB  - Juvenile dermatomyositis is part of the idiopathic inflammatory myositis group of
      diseases, presenting acute or chronic multisystemic inflammatory injury, that
      mainly affects muscles and skin. It s incidence is 4/1,000,000, prevailing in
      women and Caucasians, with symptoms starting between 5 14 years of age. The
      etiology is unknown, nevertheless is well recognized the role of vasculitis
      produced by autoantibodies, such is responsible for the damage on skin and
      muscular microvasculature. The acute or chronic complications and the neuropathic
      manifestations (cerebral vasculitis and peripheric neuropathy) are rare, and both
      are the result of the same autoimmune vasculitis injury.

PMID- 11988915
TI  - [Advances in the diagnosis of epilepsy].
AB  - INTRODUCTION. Over the past ten years, evaluation of epilepsy has changed
      drastically thanks to the development of diagnostic procedures which have
      transformed understanding of the neurophysiological basis of the development of
      convulsive seizures. In the USA alone 2 million people are affected by this
      disease. Of these approximately 20% continued to have seizures in spite of
      receiving medical treatment. This means that the condition is of a priority for
      public health attention in any country. Technology used in many areas of
      diagnosis has allowed the patient with epilepsy to be managed in a much more
      integrated manner, and therefore to have better possibilities regarding  quality
      of life . DEVELOPMENT. We define these technological advances in three areas in
      which progress has fortunately been outstanding. Firstly, obtention of better
      anatomical and functional images permit correlation of the pathology with a
      specific type of epileptogenic activity. Secondly, understanding the electro
      clinical semiology resulting from the generation of abnormal cortical activity
      with subsequent activation of different areas of the cerebral cortex, has made it
      possible to treat epilepsy surgically. Finally the discovery of genes affecting
      the presentation of a particular epilepsy syndrome defines the diagnosis and give
      orientation as to treatment and prognosis in particular cases.

PMID- 11988916
TI  - [Prevention of epilepsy].
AB  - OBJECTIVE: To review the preventive and prophylactic aspects of epilepsy.
      DEVELOPMENT: The description of the prevention of the causes of epilepsy includes
      the measures to prevent epilepsy and epileptic seizures. The concept of
      antiepileptogenesis is discussed according to the available information about the
      role that both the classic and new antiepileptic drugs (AEDs) play in this
      process. Neuroprotection is discussed in the context of the mechanisms of action
      of the AEDs and of the mechanisms of neuronal lesion produced by the causes of
      epilepsy or by the seizures themselves. Among the new therapeutic modalities the
      current knowledge about the vagus nerve stimulator and the surgical treatment is
      summarized. The potential future therapeutic modalities include alternative
      medicine, pharmacologic treatment of the epileptogenic focus, genetic treatment
      and vaccination. CONCLUSIONS: The first step in preventing epilepsy is to avoid
      the causes or the risk factors. Some classic AEDs have demonstrated to be
      effective in the prophylaxis of provoked seizures (acute, symptomatic) but not of
      unprovoked seizures (epileptic). The best knowledge of the pathogenesis and the
      molecular and biological basis of epileptogenesis secondary to lesional causes,
      suggest that antioxidant and neuroprotective agents, including the new AEDs, may
      prevent epilepsy. There is a need to design studies with the goal of
      demonstrating their antiepileptogenic and/or neuroprotective activity at
      different ages in life. New and future therapeutic modalities may offer
      additional preventive options.

PMID- 11988917
TI  - [Cerebrovascular disease and atmospheric pressure].

PMID- 11988918
TI  - [Admission to the home for patients with cerebral ictus in Sagua la Grande,
      Cuba].

PMID- 11988919
TI  - The nerve under the microscope.

PMID- 11988920
TI  - The results of microneurosurgery of the inferior alveolar and lingual nerve.
AB  - PURPOSE: The goal was to evaluate the experience of one surgical unit during a 5
      year period in the evaluation and management of patients with injuries of the
      inferior alveolar and lingual nerve with particular reference to indications for
      and results of microneurosurgery. PATIENTS AND METHODS: This study includes all
      patients referred with a diagnosis of injury to the inferior alveolar or lingual
      nerve during 5-year period from January 1, 1994, to January 1, 1999. All patients
      were evaluated with Frey's hairs for touch and direction sense, 2-point
      discrimination, and hot and cold water and Minnesota thermal discs for
      temperature sensation. Patients who fulfilled certain specified criteria were
      offered microneurosurgery, and the results were evaluated for those who underwent
      microneurosurgery. RESULTS: The study consisted of 880 consecutive patients; 96
      were thought to fulfill the criteria for microneurosurgery. Of these, 51
      underwent microneurosurgical exploration and repair. In 5 patients, no injury
      could be detected at surgery, and no corrective surgery was performed other than
      decompression. In 26 patients, excision and direct anastomosis were performed,
      and in an additional 20 patients, nerve gap reconstruction was performed. In 16
      of these 20 patients, reconstruction was performed with an autogenous vein graft,
      and in 2 patients, a Gore-Tex tube graft (W.L. Gore & Associates, Inc, Flagstaff,
      AZ) was used to bridge the nerve gap. In 2 patients, an autogenous nerve was
      used. Thirty-four of the repairs were made on the lingual nerve, and 17 were made
      on the inferior alveolar nerve. With the use of established criteria, 10 patients
      were considered to have had a good improvement in sensation, 18 patients were
      considered to have had some improvement in sensation, and 22 patients were
      considered to have had no improvement in sensation; 1 patient reported an
      increase in dysesthesia after surgery. The semiobjective assessment of patients
      did not always correspond with the patients' subjective evaluation. CONCLUSION:
      In a relatively small study in selected cases, microneurosurgery can provide a
      reasonable result in improving sensation in the inferior alveolar and lingual
      nerve. More than 50% of patients experienced some improvement in sensation, and
      dysesthesia did not develop after surgery in any patient who did not have it
      before surgery.

PMID- 11988921
TI  - Relationship of the mandibular canal to the lateral cortex of the mandibular
      ramus as a factor in the development of neurosensory disturbance after bilateral
      sagittal split osteotomy.
AB  - PURPOSE: This study evaluated the location of the mandibular canal in the ramus
      of the mandible before bilateral sagittal split ramus osteotomy and examined its
      relationship with postoperative neurosensory disturbance. PATIENTS AND METHODS:
      The subjects consisted of 20 patients undergoing bilateral sagittal split ramus
      osteotomy. Before surgery, the region from a plane containing the lowest point of
      the mandibular foramen to 22 mm below it was observed on transaxial computed
      tomograms acquired with a slice thickness of 2 mm and a slice interval of 2 mm.
      The relationship between the distance from the mandibular canal to the external
      cortical bone and neurosensory disturbance in the lower lip or mentum more than 1
      year after surgery was evaluated. RESULTS: The mandibular canal came into contact
      with the external cortical bone on 10 sides (25%); neurosensory disturbance
      occurred on all these sides, an incidence significantly greater than that (20%)
      on the 30 sides (75%) without contact between the canal and the external cortical
      bone (P <.05). In patients with mandibular canal/external cortical bone contact,
      the vertical extent of contact ranged from 2 to 18 mm (mean, 10.6 +/- 4.9 mm).
      Neurosensory disturbance was significantly more likely to be present 1 year after
      surgery, when the width of the marrow space between the mandibular canal and the
      external cortical bone was 0.8 mm or less (P <.002). CONCLUSIONS: The increased
      risk of neurosensory disturbance associated when there is contact between the
      mandibular canal and the external cortical bone should be considered when
      sagittal split ramus osteotomy is performed.

PMID- 11988922
TI  - Minor complications arising in alveolar distraction osteogenesis.
AB  - PURPOSE: This study evaluates complications that arise during mandibular alveolar
      distraction osteogenesis and suggests treatments. METHODS: We monitored
      complications that arose during alveolar distraction osteogenesis in 5 patients
      who underwent a total of 7 distractions, in all cases using an intraosseous
      distractor (Lead System, Leibinger, Germany). We report our responses to each
      type of complication. RESULTS: All 7 distractions were followed by the placement
      of 2 implants. The restoration was ideal in 4 of the 7 cases and functional but
      not ideal in the remaining 3. In all 7 distractions, we observed complications,
      although many were minor complications readily avoided by the use of appropriate
      technique. The complications were, first, intraoperative complications, namely 1)
      fracture of the transport segment (1 of 7 cases; RESPONSE: appropriate
      preventative measures), 2) difficulties in finishing the osteotomy on the lingual
      side (7 of 7 cases; RESPONSE: use of fine chisels made from cement spatulas), and
      3) excessive length of the threaded rod (1 of 7 cases; RESPONSE: cut the rod).
      Second, complications arose during distraction: 1) incorrect direction of
      distraction (2 of 7 cases; no corrective measures necessary in the present
      cases), 2) perforation of the mucosa by the transport segment (2 of 7 cases;
      response: smooth the crest of the segment with a bone rongeur), and 3) suture
      dehiscence (1 of 7 cases; no significant implications). Third, there were
      postdistraction complications, namely bone formation defects (4 of 7 cases;
      response: guided bone regeneration). CONCLUSIONS: A number of complications may
      arise during alveolar distraction osteogenesis. Most of these complications can
      be considered minor and are readily avoided or resolved by the use of appropriate
      procedures.

PMID- 11988923
TI  - The impact of bilateral sagittal split osteotomy on mandibular width and
      morphology.
AB  - PURPOSE: In this study, we examined mandibular width before and 1 year after
      bilateral sagittal split osteotomy. PATIENTS AND METHODS: Forty-two patients (28
      females and 14 males) underwent bilateral sagittal split osteotomy. Fifty-six
      points or angles on the lateral cephalogram and 15 points or angles in the
      posteroanterior cephalogram were obtained before surgery and 1 year after
      surgery. Mandibular width was measured on the posteroanterior cephalogram (from
      gonion to gonion [Go to Go]). Changes in mandibular width were also measured by
      monitoring changes in an angle formed between a constructed line along the
      outside of the left and right ascending rami of the mandible and the facial
      midline. Association of the mandibular width with a variety of standard skeletal
      parameters was calculated. RESULTS: Mandibular width increased from 99.7 +/- 7.2
      mm (mean +/- SD) to 101.1 +/- 6.1 mm. It remained unchanged in 17 patients,
      increased in 23 patients, and decreased in 2 patients. Analysis revealed a
      significant inverse correlation of the changes in mandibular width with the
      changes in posterior facial height (P =.05) and a significant positive
      correlation with the angle formed by the facial midline and the left ascending
      ramus (P >.005). All other changes were not significantly correlated with the
      changes in mandibular width. Multiple regression analysis revealed that the
      change in posterior facial height is an independent parameter for the changes in
      mandibular width (P =.041 for mandibular width at Go-Go). CONCLUSIONS: This study
      establishes a clinically important association between frontal view parameters
      with parameters derived from lateral view analysis.

PMID- 11988925
TI  - Temporomandibular joint "open lock" versus condylar dislocation: signs and
      symptoms, imaging, treatment, and pathogenesis.
AB  - PURPOSE: In the temporomandibular joint (TMJ) "open-lock" condition the condyle
      is entrapped in front of the lagging disc and cannot slide back under the fossa.
      The aim of this retrospective study was to describe the signs and symptoms and
      imaging of TMJ "open lock" versus condylar dislocation and clarify its
      pathogenesis. The study stresses the efficacy of arthrocentesis in restoring the
      functional capacity of the joint, while obviating the need for surgical
      intervention. PATIENTS AND METHODS: The study included 5 patients (3 females and
      2 males; ages ranging from 11 to 26 years) presenting 6 open-lock joints that did
      not respond to conservative treatment. The TMJs postarthrocentesis status in 5
      joints (follow-up period, 6 to 32 months) was determined by patient self
      assessment and clinical examination. RESULTS: Five TMJs had recurrent open lock
      and were treated by arthrocentesis. They reacted favorably to the treatment and
      the open-lock events were eliminated. The first case was apparently misdiagnosed
      as condylar dislocation, and unnecessary surgical intervention was performed.
      CONCLUSIONS: Arthrocentesis is a safe and rapid procedure that prevents
      recurrence of open-lock conditions. This disorder should be distinguished from
      recurrent condylar dislocation, which requires surgical intervention.

PMID- 11988927
TI  - Do mandibular third molars alter the risk of angle fracture?
AB  - PURPOSE: In this study, we measured the relationship between the presence of
      mandibular third molars (M3s) and angle fractures. In addition, the study
      examined the relationship between M3 impaction level and angle fracture
      susceptibility. PATIENTS AND METHODS: We used a multicenter retrospective cohort
      study design and a sample composed of patients treated for mandibular fractures.
      The predictor variables were 1) the presence of an M3 and 2) the position of an
      M3 classified according to the Pell and Gregory system. The outcome variable was
      the presence or absence of an angle fracture. RESULTS: The study sample was
      composed of 1,210 patients. Patients with M3s present had a 2.1 times greater
      chance of an angle fracture than did patients without M3s (P <.001). There was a
      statistically significant variation in the risk for an angle fracture depending
      on M3 position (P <.001). CONCLUSIONS: In patients who sustain a mandible
      fracture, the presence of M3s significantly increases the likelihood of an angle
      fracture. In addition, the risk for an angle fracture depends on M3 position.

PMID- 11988928
TI  - A review of 56 cases of chronic closed lock treated with temporomandibular joint
      arthroscopy.
AB  - PURPOSE: The aims of this prospective clinical study were to look at the features
      that constitute chronic closed lock of the temporomandibular joint (TMJ) and to
      assess the effectiveness of TMJ arthroscopic lavage and lysis in the management
      of this condition. PATIENTS AND MATERIALS: Sixty joints in 56 patients who
      presented with mandibular hypomobility suggestive of chronic closed lock were
      prospectively examined and treated with TMJ arthroscopic lavage and lysis during
      a 3-year period from 1996 to 1999. RESULTS: Eighty-seven percent (49 of 56) of
      patients were found to have chronic closed lock of the TMJ. The most common intra
      articular findings were fibrillation (76%) and synovitis (54%). TMJ arthroscopic
      lavage and lysis were found to be effective in the management of chronic closed
      lock in 84% (47 of 56) of patients, with an average 66% reduction in pain levels
      and a mean improvement of 9.8 mm in interincisal mouth opening up to 6 weeks
      after the procedure. CONCLUSIONS: Chronic mandibular hypomobility is a clinical
      sign that is often but not always caused by chronic closed lock of the TMJ. The
      intra-articular findings of this study suggest that cartilage degradation and
      synovial inflammation are important components of chronic closed lock of the TMJ
      that respond well to arthroscopic lavage. Patients with mandibular hypomobility
      not caused by closed lock of the TMJ (ie, myofascial pain and dysfunction,
      osteoarthrosis, and others) are less likely to derive benefit from arthroscopic
      lavage and lysis, so other treatment methods should be considered.

PMID- 11988930
TI  - Obstructive sleep apnea and maxillomandibular advancement: an assessment of
      airway changes using radiographic and nasopharyngoscopic examinations.
AB  - PURPOSE: The study aim was to evaluate the resultant changes in the upper airway
      after maxillomandibular advancement (MMA) for obstructive sleep apnea. METHODS:
      Twelve patients were evaluated before and after MMA using fiberoptic
      nasopharyngoscopy (NPG) with Muller maneuver. An inspiratory force meter was used
      to ensure the consistency of the inspiratory efforts between the 2 examinations.
      Preoperative and postoperative lateral cephalometric radiographs were also
      compared. RESULTS: Decrease in the airway obstruction was shown by the lateral
      cephalometric radiograph as well as by fiberoptic NPG during passive respiration.
      Fiberoptic NPG with Muller maneuver also revealed a decrease in airway
      collapsibility. Although the retrodisplacement of the tongue base was improved,
      the improvement in lateral pharyngeal wall stability was the most striking.
      CONCLUSIONS: MMA achieved expansion of the upper airway. In addition, MMA
      decreased the collapsibility of the airway, especially the lateral pharyngeal
      walls. These findings may explain the highly successful outcomes of MMA for the
      treatment of obstructive sleep apnea.

PMID- 11988932
TI  - Prevalence of p53, bcl-2, and Ki-67 immunoreactivity and of apoptosis in normal
      oral epithelium and in premalignant and malignant lesions of the oral cavity.
AB  - PURPOSE: Loss of normal p53 is correlated to the progression of several
      preneoplastic lesions to neoplasms, and overexpression of bcl-2 determines an
      alteration of programmed cell death. There is an increased awareness of the
      importance of apoptosis in cancerogenesis, and a strong correlation of Ki-67 with
      high tumor grade has been reported. MATERIALS AND METHODS: The aim of our study
      was to investigate immunohistochemically the expression and relationship of p53,
      bcl-2, MIB-1, and the apoptotic index (AI) in normal oral epithelium,
      leukoplakia, dysplasia, and oral squamous cell carcinoma. RESULTS: A strong
      correlation was found between p53 overexpression and cell proliferation (MIB-1)
      and the AI. An inverse relationship was found between bcl-2 expression and MIB-1
      and AI. A significant inverse relationship was found between p53 and bcl-2. A
      good positive correlation was present between AI and MIB-1 expression.
      CONCLUSIONS: Apoptosis could be important to help to understand oral
      carcinogenesis.

PMID- 11988933
TI  - Evaluation of the effect of heterologous type I collagen on healing of bone
      defects.
AB  - PURPOSE: The purpose of this investigation was to evaluate the effect of type I
      collagen on the healing of bone defects both experimentally and clinically.
      MATERIALS AND METHODS: In the experimental study, 16 adult male rabbits were
      divided into 2 groups: a collagen group and a control group. After the induction
      of general anesthesia with intraperitoneal ketamine, the anterior surfaces of
      tibias of the rabbits were surgically exposed, and a hole 4 mm in diameter was
      made in each tibia. In the collagen group, the defects were filled with type I
      collagen. The unfilled defects of the other animals were used as controls. During
      the study, the serum alkaline phosphatase activity of the rabbits, and
      radiopacity changes in the radiographs of the tibias of the rabbits were
      evaluated. The rabbits were killed on the 35th day, and histologic sections of
      the tibias were prepared. The clinical study was carried out on periapical
      defects in a total of 15 patients who underwent apicoectomy. After the surgical
      procedure, the osseous defects in periapical regions of 7 patients were filled
      with type I collagen. The unfilled cavities of the other patients were used for
      control purposes. The patients were evaluated clinically and radiographically in
      the postoperative period. The data were analyzed by Student's t-test and Mann
      Whitney U test. RESULTS: In the experimental study, there was an increase in
      radiopacity corresponding with the serum alkaline phosphatase activity, and there
      were statistically significant differences between the control and collagen
      groups both radiologically and biochemically on the 14th and 28th days of the
      study. In the clinical study, the control cavities filled with a tissue of normal
      bone density in about 5 months, but the collagen cavities filled in 3 months.
      CONCLUSIONS: It was determined that heterologous type I collagen provides a more
      rapid regeneration of bone defects.

PMID- 11988934
TI  - Biomechanical response of retrodiscal tissue in the temporomandibular joint under
      compression.
AB  - PURPOSE: The present study was conducted to investigate the biomechanical
      response of bovine retrodiscal tissue of the temporomandibular joint (TMJ) in
      compression. PATIENTS AND METHODS: Using 10 retrodiscal tissues obtained from 10
      cattle, the viscoelastic response of the retrodiscal tissue was evaluated by
      means of stress-strain analyses. These compressive strains were produced at a
      high strain rate and were kept constant during 5 minutes for stress-relaxation.
      RESULTS: Although the stress-strain relationship in the retrodiscal tissue was
      essentially nonlinear represented by a quadratic or power function of strain, a
      linear model could reasonably represent its elastic property. In this case, the
      instantaneous and relaxed moduli were 1.54 and 0.21 MPa, respectively. The stress
      relaxation curve showed a marked drop in load during the initial 10 seconds, and
      the stress reached a steady nonzero level. Furthermore, when using Kelvin's
      model, a satisfactory agreement can be obtained between the experimental and
      theoretical stress-relaxation curves. CONCLUSION: It is concluded that bovine
      retrodiscal tissue has a great capacity for energy dissipation during stress
      relaxation, although it has little or no function to pull the articular disc
      back.

PMID- 11988935
TI  - Biomechanical changes in the head associated with penetrating injuries of the
      maxilla and mandible: an experimental investigation.
AB  - PURPOSE: In this experiment, we studied the craniocerebral injury that occurs due
      to the transmission of forces when maxillofacial gunshot wounds are sustained by
      the facial bones and cranium. MATERIALS AND METHODS: Forty fresh pigs' heads were
      wounded by one of the following methods: steel spheres weighing 1.03 g at an
      impact velocity of 1,400 m/s, steel spheres weighing 1.03 g at an impact velocity
      of 800 m/s, M193 military bullets, or M56 military bullets. Pressure waves in the
      brain, acceleration of the head, and stress changes in the facial bones and
      cranium at the moment of the impact were recorded by pressure and acceleration
      transducers and strain gauges and were statistically compared. RESULTS: Some
      obvious differences between the mechanical values obtained from high-and low
      velocity missile wounds were found. A negative relationship between the peak
      value of the pressure wave in the brain and the distance from the point of impact
      to the transducer was obtained. The acceleration of the head in the direction of
      the ballistic path was the strongest in absolute value. There were differences in
      the stress values between the mandible and the temporal bone. CONCLUSIONS:
      Acceleration of the head, pressure wave changes in the brain, and injury from
      bony stress conduction all play important roles in associated craniocerebral
      damage after maxillofacial firearm wounds.

PMID- 11988937
TI  - Anesthetic management for advanced rheumatoid arthritis patients with acquired
      micrognathia undergoing temporomandibular joint replacement.

PMID- 11988938
TI  - Use of the fibula free flap in maxillary reconstruction: a report of 3 cases.

PMID- 11988939
TI  - Injury to the inferior alveolar nerve due to thermoplastic gutta percha.

PMID- 11988940
TI  - Severe facial ischemia after endodontic treatment.

PMID- 11988941
TI  - Congenital midline cervical cleft: case report and review.

PMID- 11988942
TI  - Warthin's tumor with multiple sarcoid-like granulomas: a case report.

PMID- 11988943
TI  - Spontaneous regression of cutaneous melanoma with subsequent metastasis.

PMID- 11988944
TI  - The utility of helical computed tomography Tooth Pix and a 3-dimensional life
      size model for treatment of squamous cell carcinoma of the mandible: a case
      report.

PMID- 11988945
TI  - Use of vinyl polysiloxane impression material as an extraoral obturator for
      orocutaneous fistulas.

PMID- 11988946
TI  - Use of a bone wax analogue to determine the amount of chin bone needed for sinus
      augmentation.

PMID- 11988947
TI  - Posterior transpalatal distraction osteogenesis.

PMID- 11988949
TI  - Introduction: cardiac surgery for heart failure.

PMID- 11988950
TI  - Coronary bypass in left heart failure.
AB  - Clinical experience is accumulating that coronary artery bypass grafting is of
      great benefit in patients with advanced ischemic cardiomyopathy. At Yale
      University, we have analyzed short- and long-term results in 188 consecutive
      patients with an ejection fraction (EF) of 30% or less undergoing coronary artery
      bypass grafting by a single surgeon. This experience permits the following
      conclusions: (1) Surgery can be performed safely (mortality 2.8% in elective
      patients); (2) Major improvement in left ventricular (LV) function is objectively
      demonstrable (EF change from 23.3% to 33.2%); (3) Symptomatic improvement is
      noted by patients (NYHA class change from 3.1 to 1.4); and (4) Good long-term
      survival is realized, relative to expectations with medical management alone
      (88%, 77%, and 60% at 1, 3, and 5 years). If coronary artery disease is severe
      and proximally situated and there are adequate target arteries, we do not deny
      patients surgery based on EF or LV size criteria, nor do we require objective
      demonstration of reversible ischemia. In fact, hearts in the largest size range
      (left ventricular end-systolic volume index > 100 mL) actually showed beneficial
      reverse remodeling subsequent to coronary artery bypass grafting. Surgical
      revascularization is recommended strongly for patients with advanced ischemic
      cardiomyopathy. Results rival those of transplantation.

PMID- 11988951
TI  - Mitral valve surgery in the patient with left ventricular dysfunction.
AB  - Mitral regurgitation (MR) is a frequent complication of end-stage cardiomyopathy.
      Historically, these patients were managed either medically or with mitral valve
      replacement, both associated with poor outcomes. We studied 125 patients with
      cardiomyopathy and severe MR who were managed with mitral reconstruction. One
      hundred twenty-five patients with 4+ MR, left ventricular ejection fractions from
      8% to 24% (mean 14%), and New York Heart Association class III or IV symptoms
      were prospectively studied. All patients underwent mitral valve repair with an
      undersized flexible annuloplasty ring. There was one intraoperative death and
      five 30-day mortalities. Intraoperative echocardiography showed mild to trivial
      MR in seven patients, and no residual MR in the majority of patients. There were
      26 late deaths; three of these patients had progression of the disease and
      underwent transplantation. One- and 2-year actuarial survival has been 80% and
      70%, respectively. New York Heart Association class has improved for all the
      patients from a preoperative mean of 3.2 +/- 0.2 to 1.8 +/- 0.4 postoperatively.
      At 24-month follow-up, all patients showed an improvement of ejection fraction,
      cardiac output, and end-diastolic volumes, along with a reduction in sphericity
      index and regurgitant volume. Mitral valve repair with an undersized flexible
      annuloplasty ring is a safe and effective approach to correct MR in
      cardiomyopathy patients. All observed changes contribute to reverse remodeling
      and the restoration of the normal left ventricular geometric relationship. Mitral
      reconstruction offers a new treatment strategy for patients with MR and end-stage
      heart failure.

PMID- 11988952
TI  - Aortic valve surgery in patients with left ventricular dysfunction.
AB  - Patient with advanced left ventricular dysfunction and heart failure symptoms,
      either secondary to severe aortic stenosis and a low transvalvular gradient, or
      chronic aortic insufficiency are sometimes referred for cardiac transplantation.
      Now, with improvements in both myocardial protection and better valve prostheses,
      aortic valve surgery for patients with even the most advanced ventricular
      dysfunction can be performed with low risk.

PMID- 11988953
TI  - Left ventricular reconstruction for ischemic cardiomyopathy.
AB  - An outline of the Toronto General Hospital's philosophy for revascularization and
      left ventricular reconstruction in patients with ischemic cardiomyopathy. An open
      beating heart technique with modified linear closure and septoplasty when
      indicated is used for repair of both akinetic and dyskinetic scar. Patient
      selection, OR mortality (2.6%), and long-term results are reviewed.

PMID- 11988954
TI  - Passive constraint and new shape-change devices for heart failure.
AB  - Lessons learned from ventricular remodeling procedures have shown that Laplace
      mechanics, whereby mural tension is related to ventricular diameter, may be
      beneficially applied to the left ventricle (LV). Recently developed devices,
      predicated on the Law of Laplace, are directed at interrupting the heart-failure
      cascade without removing functioning myocardium. The Acorn cardiac support device
      is a polyester-mesh jacket placed snugly around the heart to provide end
      diastolic support and prevent LV dilation. The Myosplint device uses transmural
      tension members to bisect the dilated LV to create a bilobed LV with decreased
      mural tension in each cavity. Preclinical and early clinical data with both
      devices appears promising and may offer a new surgical alternative for patients
      with worsening heart failure.

PMID- 11988955
TI  - Cell transplantation for the treatment of heart failure.
AB  - Along with angiogenesis and gene therapy, cell transplantation is one of the
      newest treatment modalities proposed to improve the outcome of patients with
      cardiac failure. Both experimental and clinical data have now established that
      implantation of contractile cells into fibrous postinfarction scars can allow
      them to regain some functionality. Primarily for practical reasons, autologous
      skeletal myoblasts have been the first to be tested in a clinical trial, but
      other cell types can be considered among which bone marrow stromal and
      hematopoietic stem cells are of particular interest because of their presumed
      pluripotentiality and the possibility to use them as autografts. However, several
      key issues still need to be addressed including: (1) the advantages and
      disadvantages of these different donor cells; (2) the extent to which cell
      engraftment affects cardiac function actively (ie, by increasing contractility)
      or passively (ie, by limiting infarct expansion and remodeling); (3) the
      development of strategies targeted at enhancing cell survival; and (4) the
      identification of cardiac diseases for which cell engraftment may be most
      beneficial. In parallel to the numerous experimental studies designed to address
      these issues, initial clinical trials are underway or in preparation and it is
      mandatory to design and conduct them in a careful manner so as to ultimately know
      whether cellular transplantation holds its promise as a means of improving the
      outcomes of patients with heart failure.

PMID- 11988956
TI  - Targeted gene therapy for the treatment of cardiac dysfunction.
AB  - Congestive heart failure (CHF), one of the leading cardiovascular disorders in
      developed countries, remains a significant therapeutic challenge. Efficacious
      therapies are few, and the incidence of CHF and associated death rates continue
      to rise. An interest in the novel therapeutic approach of gene therapy for the
      treatment of CHF has emerged. Essential elements of successful gene therapy
      include an appropriate vector for delivering and expressing the gene within the
      target cell, an optimal protocol for delivery of the gene, and the identification
      of relevant pathways and molecular targets. Interest in gene therapy for CHF has
      been directed towards improving cardiomyocyte function through optimization of
      calcium homeostasis and beta-adrenoreceptor function, and preclinical studies
      have shown encouraging results. This review will discuss the vectors and
      mechanisms of gene delivery as well as potential molecular targets for the
      treatment of CHF.

PMID- 11988957
TI  - Mechanical circulatory support: new advances, new pumps, new ideas.
AB  - Mechanical circulatory support (MCS) is a viable therapy for severe end-stage
      heart disease. Most obstacles to long-term MCS therapy have been overcome, and a
      number of clinical trials, including the recent REMATCH trial, have shown a clear
      benefit in terms of survival and improved quality of life. MCS should therefore
      no longer be considered as simply a temporary bridge to other therapies, but also
      a destination therapy whose potential should continue to expand through the
      development and use of newer, more innovative devices such as continuous flow
      pumps, next-generation centrifugal pumps, and total artificial hearts. The
      homebound heart failure patient and the patient facing imminent death from
      massive myocardial infarction receive little statistical benefit from current
      therapies, and the new and evolving MCS technologies offer the potential for
      effective therapy to these desperately ill patients.

PMID- 11988958
TI  - Synergistic approaches in the surgical treatment of heart failure: complex
      solutions for complex problems.
AB  - In the current era, with a high incidence and prevalence of heart failure,
      cardiologists are developing a wide range of medical therapies for this
      population. Working in synergy with pharmacologic therapies, surgeons are
      developing several innovative surgical procedures to address mechanical problems
      in heart failure patients that will stabilize and reverse the complex problem of
      heart failure.

PMID- 11988959
TI  - AIDS summit in South Africa.

PMID- 11988960
TI  - [Antiprogestin to clinical use].

PMID- 11988961
TI  - [COX-2 inhibitor to whom?].

PMID- 11988962
TI  - [Early termination of pregnancy with pharmacological means].

PMID- 11988963
TI  - [Effects of alcohol on health].

PMID- 11988964
TI  - [Cognitive aging].

PMID- 11988965
TI  - [The role of immune deficiency in cartilage-hair hypoplasia].

PMID- 11988966
TI  - [Fever, rash and jaundice in a 10 year-old boy].

PMID- 11988967
TI  - [How to treat burn-out].

PMID- 11988968
TI  - [Recurrent facial palsies in a young woman].

PMID- 11988969
TI  - [Fundamentalism versus evolution].

PMID- 11988970
TI  - [Should even youngsters spend the Winter in the equator?].

PMID- 11988971
TI  - [Vitamin D and the elderly].

PMID- 11988972
TI  - [Corticosteroid treatment in threatening preterm delivery].

PMID- 11988973
TI  - Identification and care of substance-dependent neonates.
AB  - Identification and care of substance-dependent neonates requires a holistic,
      family-centered approach to care, starting in the prenatal period and continuing
      long after the infant is born. Interventions useful in working with families of
      substance-dependent neonates include psychological support, substance abuse
      treatment, and physiologic support in the form of nonpharmacologic and
      pharmacologic therapies. The nurse can play a powerful role in determining the
      fate of each family. Early recognition of the problem and appropriate, decisive
      intervention is necessary if the long-term outcomes of substance dependence are
      to be improved.

PMID- 11988974
TI  - Laboratory sampling. Alternate site perspectives.
AB  - Laboratory test results are a major diagnostic tool in the determination of a
      patient's condition. Clinical decisions and treatment regimens are based on these
      results. Laboratory testing requires a complex combination of skill, knowledge,
      planning, and attention to details for the end result to be an accurate
      representation of the patient's condition at a specific point in time. Competency
      in techniques, knowledge of the purpose of the testing, effects of variables on
      laboratory results, and the importance of following quality standards are
      imperative. Alternate sites present many challenges to laboratory testing.
      Physicians' offices, clinics, and patient's homes are rapidly replacing the
      traditionally controlled laboratory setting. Point-of-care technology has
      addressed many of the logistical problems inherent in laboratory testing for the
      alternate site; however, competence and quality assurance remain important parts
      of laboratory testing and the analysis of results.

PMID- 11988975
TI  - Clinical application of the World Health Organization analgesic ladder.
AB  - One resource that has spurred the development of new standards for the assessment
      and treatment of pain is the World Health Organization (WHO) analgesic ladder, a
      three-step guide to the administration of analgesia and adjuvant medication for
      the treatment of pain. Correct application of the ladder is dependent upon
      knowledge of the interactions and side effects of the nonsteroidal anti
      inflammatory drugs, opioids, and adjuvants recommended at each step of the
      ladder. Equianalgesic conversion can help provide correct dosing when changing
      opioids. Because of their altered metabolism and increased risk for epigastric
      complications, the elderly should receive special consideration when such
      medications are administered.

PMID- 11988976
TI  - A story on childhood immunization practices, complete with camera footage of a
      nurse administering "a shot" to a child without using personal protective
      equipment.

PMID- 11988977
TI  - Fluid resuscitation in acutely injured patients.
AB  - Injuries are the third leading cause of death in the United States, exceeded only
      by heart disease and cancer. The success of resuscitation after an acute injury
      is dependent on providing adequate oxygenation, restoring intravascular fluid
      volume, and maintaining optimum cardiac output and cellular perfusion. Fluid
      resuscitation is essential to the successful management of hemorrhagic shock; it
      involves obtaining venous access, administration of the appropriate type and
      amount of fluid and blood products, and ongoing monitoring of the patient. There
      are special considerations in fluid resuscitation for the pediatric and burn
      patient. Care of the trauma patient is a dynamic process and requires ongoing
      evaluation of clinical parameters. Fluid resuscitation is a central component in
      the overall management of the trauma patient.

PMID- 11988978
TI  - Silicone catheter fracture secondary to stress events and a dressing technique to
      reduce those events.
AB  - In vitro experiments describe how two specific stresses result in weakened and
      thus more easily fractured silicone catheters. The two stresses studied are
      stretching and kinking of the catheters. A dressing method for flexible
      peripherally inserted catheters that eliminates kinking and significantly reduces
      stretching is described. The dressing method is compared experimentally with a
      standard dressing method.

PMID- 11988979
TI  - The role of the perfusionist.
AB  - During open heart procedures, the heart is stopped. The surgeon needs a blood
      free, motionless work area. The heart-lung bypass machine provides circulation
      for the rest of the body during surgery. The perfusionist, as an active member of
      the surgical team, operates the heart-lung bypass machine. Historical development
      of the perfusionist's role and collaboration with other members of the healthcare
      team are discussed.

PMID- 11988980
TI  - A sociocultural health model for late-in-life immigrants.
AB  - This study develops a sociocultural health and illness model for Iranian late-in
      life immigrants in Sweden by analyzing ways in which they perceive, experience,
      and explain their health situations. Fifteen Iranian immigrants, ages 55 to 80,
      were interviewed; data were analyzed using the interpretive-phenomenology method.
      The interviews revealed the following concepts: Reflections on the meaning of
      health were interpreted as cultural understanding of health. Reflections
      expressing knowledge about preventing illness and maintaining health were
      interpreted as proposed strategies and beliefs. Reflections expressing how to
      prevent illness and maintain health were interpreted as practical strategies,
      which were based on understanding of cultures and were contingent on immigration.
      Health care providers might use the resulting model to assist patients and
      families in appropriating cures and symptom management to support patients' sense
      of well-being.

PMID- 11988981
TI  - Factors affecting maternal role attainment among low-income, Thai, HIV-positive
      mothers.
AB  - This phenomenological study used content analysis of interview data to explore
      factors affecting maternal role attainment in a convenience sample of 39 low
      income, Thai, HIV-positive mothers selected for their successful adaptation. All
      mothers reported feeling comfortable in their maternal roles and achieved greater
      than 80% of the total score on the Maternal Behavioral Questionnaire. In-depth
      interviews were conducted regarding the life experience of the mothers. The
      results revealed the mothers' uses of internal and external resources to attain
      their maternal roles. Six factors were identified: (a) setting a purpose for
      life, that is, to raise the infant; (b) keeping secrets from others; (c) a
      feeling of normalization; (d) having good quality of support from others; (e)
      having hope for an HIV cure; and (f) receiving accessible, pleasant health
      services that protect anonymity regarding HIV status. The results suggest that
      nurses can promote maternal role attainment by supporting the mothers' management
      style.

PMID- 11988982
TI  - Stranger to friend enabler: creating a community of caring in African American
      research using ethnonursing methods.
AB  - African Americans are facing a serious health crisis. They are disproportionately
      affected by most chronic illnesses. The disparity among ethic groups as it
      relates to health and illness is related to psychosocial and biological factors
      within the African American culture. Many African Americans are sometimes
      reluctant to participate in studies. This article discusses the process of
      creating a caring community when conducting research within an African American
      community based on the experience of the authors with two faith communities in a
      southern metropolitan area in the United States. The process is identified as
      unknowing, reflection, presence, and knowing. The process is based on Leininger's
      theory of culture care diversity and universality and her stranger to friend
      enabler. When the theory and method are used, the investigator moves from a
      stranger within the community to a trusted friend and begins to collect rich and
      valuable data for analysis from the informants' point of view.

PMID- 11988983
TI  - Guatemalans' practices for health promotion and the meaning of respect afforded
      them by health care providers.
AB  - This descriptive study, the second part of a multinational study of Central
      Americans and Mexicans, describes Guatemalans' practices for health promotion and
      wellness, disease and illness prevention, and the meaning of respect afforded
      them by health care providers. Understanding a person's beliefs and values when
      planning nursing and health care interventions helps the caregiver provide
      culturally acceptable care that improves clients' satisfaction and health status.
      Culturally respectful, acceptable, and appropriate care conserves the utilization
      of human, material, and financial resources. There were 25 participants in this
      sample. This study uses selected primary and secondary characteristics of culture
      and selected domains from the Purnell model for cultural competence as guides for
      questionnaire development, review of the literature, data analysis, and
      discussion of the findings.

PMID- 11988984
TI  - Developing cultural competence in the baccalaureate nursing student: a population
      based project with the Hutterites.
AB  - The purpose of this article is to articulate the process of educating
      baccalaureate students to apply culturally competent, population-based nursing
      care to the Hutterites. The Hutterites are a German dialect-speaking,
      ethnoreligious population. Campinha-Bacote's culturally competent model guided
      the student learning process. Groups of students developed culture-specific,
      population-based assessment models to identify the health-related needs of the
      Hutterites. One example of a Hutterite health assessment model that was derived
      from Dever's epidemiologic model and Purnell and Paulanka's model for cultural
      competence is presented. Priority health needs of Hutterite colonies are
      described, and examples of health programs are given. Recommendations for working
      with the Hutterite population as part of an undergraduate public health nursing
      course are put forth. The culturally congruent process of teaching and learning
      for nursing students can be applied to other health-related professions and
      adapted to other cultural contexts.

PMID- 11988985
TI  - A call for advocates for cultural awareness.

PMID- 11988986
TI  - Race, ethnicity, and geography: disparities in heart disease in women of color.
AB  - Cardiovascular disease (CVD) is the leading cause of death in women.
      Misconceptions about the importance of CVD still persist. These myths affect
      awareness of CVD and the urgency with which women present for treatment after
      symptoms develop. Modifiable and nonmodifiable risk factors are more prevalent
      among ethnic minority women in concentrated geographical locations. The recent
      publication of the CDC women's atlas presents a unique opportunity for healthcare
      providers to use derived county-specific data in education, research, and
      delivery of health promotion and disease prevention services to women of color.
      Specific recommendations for the nursing profession are provided to assist in
      eliminating CVD disparities for all women.

PMID- 11988987
TI  - Conducting research in culturally diverse inner-city neighborhoods: some lessons
      learned.
AB  - Social, behavioral, and health research among disenfranchised groups in inner
      cities poses problems in collecting data. It is a challenge to achieve data of
      sufficient quantity and quality necessary to be scientifically usable. This
      article describes the experiences of a research team during two phases of data
      collection in a mental health intervention study in New York's South Bronx.
      Challenges in addressing human subject concerns, the formation of a fieldwork
      team, enrollment and retention of respondents, and administration of instruments
      are described and solutions are discussed. Emphasis is placed on researchers'
      approaches to the selection, orientation, and safety of interviewers, interviewer
      respondent race and ethnic matching, contacts and rapport with respondents, and
      the handling of such interpersonal issues as distrust, poor cooperation, and
      family dynamics. The procedures developed took into consideration the culture and
      life conditions of the population to ensure a satisfactory response rate and high
      quality data.

PMID- 11988988
TI  - Founder's focus: theoretical, research, and clinical critiques to advance
      transcultural nursing scholarship.

PMID- 11988989
TI  - [A suicidal risk].

PMID- 11988990
TI  - [Lice and crab lice in the eye lashes].

PMID- 11988991
TI  - [Refractive surgery].

PMID- 11988992
TI  - [Avoiding the difficult and dangerous surgical procedures in order to treat
      snoring].

PMID- 11988993
TI  - [Is schizophrenia disappearing?].

PMID- 11988994
TI  - [New trends in the therapy of myeloma].

PMID- 11988995
TI  - [Hypersensitivity to electricity is not an allergy, what is it?].

PMID- 11988996
TI  - [The physician in the jungle of neuropsychological concepts].

PMID- 11988997
TI  - [When does the patient get the identity of a dying person?].

PMID- 11988998
TI  - [Half of a century of medical research in Finland].

PMID- 11988999
TI  - [Kidney failure in an elderly woman].

PMID- 11989001
TI  - [When a contraindication is actually an indication--how do we treat primary
      hyperparathyroidism in an elderly person?].

PMID- 11989000
TI  - [Meeting a patient with sleep disorder].

PMID- 11989002
TI  - [Influenza as a hospital infection--should the staff be vaccinated?].

PMID- 11989003
TI  - [The comeback of surgical treatment for Parkinson disease].

PMID- 11989004
TI  - [Brain and work].

PMID- 11989005
TI  - [Clozapine in the treatment of schizophrenia].

PMID- 11989006
TI  - [Diagnostics of bulimia and its somatic complications].

PMID- 11989007
TI  - [Do you recognize the pharyngitis and dermatitis caused by Arcanobacterium
      haemolyticum?].

PMID- 11989008
TI  - [New drug treatments for rheumatoid arthritis].

PMID- 11989009
TI  - [A patient vomiting and craving for salt].

PMID- 11989010
TI  - [Which foreign term should be discriminated?].

PMID- 11989011
TI  - [Pap, Bethesda or something else?].

PMID- 11989012
TI  - [Misrepresenting the list of qualifications--a new form of scientific fraud?].

PMID- 11989013
TI  - [Surgical treatment of ovarian cancer should be centralized].

PMID- 11989014
TI  - [When should the brain imaging be done in suspected dementia?].

PMID- 11989015
TI  - [Imaging diagnostics in early dementia].

PMID- 11989016
TI  - [The white matter of an aging person in magnetic resonance images].

PMID- 11989017
TI  - [Animal bites].

PMID- 11989018
TI  - [Pneumothorax in a smoker].

PMID- 11989019
TI  - [The varying position of emergency care].

PMID- 11989020
TI  - [Patient transfers--a forgotten part of the treatment chain?].

PMID- 11989021
TI  - [Is there a physician on board?].

PMID- 11989022
TI  - [Thrombolytic therapies in the emergency medical services].

PMID- 11989023
TI  - [Finnish Resuscitation Council's guidelines for basic resuscitation].

PMID- 11989024
TI  - [Analgesics in the emergency care].

PMID- 11989025
TI  - [The use of defibrillation in the resuscitation].

PMID- 11989026
TI  - [Can you act in an emergency situation?].

PMID- 11989027
TI  - [Fluid therapy in a traumatic hypovolemia].

PMID- 11989028
TI  - [Postresuscitation management].

PMID- 11989029
TI  - [Transportation of patient with cranial trauma].

PMID- 11989030
TI  - [Disaster and rescue operation].

PMID- 11989031
TI  - [Medically responsible physicians in the emergency care--present situation in
      various health care districts].

PMID- 11989032
TI  - The structure of health and illness in a Brazilian favela.
AB  - The purpose of this study was to describe the understanding of health and illness
      within the culture of women living in a favela (urban slum) in southeastern
      Brazil. The methodology described by Spradley structured the study. Interviews
      were conducted with 10 informants, and multiple interviews were conducted with
      the key informant. Analysis yielded a taxonomic structure for the domains of
      health and illness. Six components play a part in both health and illness:
      cleanliness, nutrition, doctor visits, herbal remedies (tomar cha), sympathetic
      magic, and spirituality. Attention to the six components is believed to be
      necessary in maintaining health. The indigenous components of health can be
      integrated into health teaching to enhance correspondence between nursing care
      and the worldview of favela residents.

PMID- 11989033
TI  - Taking love seriously: the context of adolescent pregnancy in Colombia.
AB  - Findings from a qualitative research study of the context of adolescent pregnancy
      are presented. Participants were 21 pregnant adolescents from Medellin, Colombia,
      and nearby villages in the region. Data were collected by means of 21 qualitative
      interviews, and analysis followed grounded theory procedures. The study reveals
      that adolescent pregnancy occurs in the context of a "genuine love affair" in
      which ideas of romantic love and gender rules guide young women's behaviour.
      Regarding an adolescent as immature or in a process of becoming might hinder
      adolescents' distinctive culture and circumstances. Ideas of romantic love and
      gender rules were powerful influences on those who unintentionally got pregnant.

PMID- 11989034
TI  - Critical thinking in African American mothers who care for adult children with
      HIV: a cultural analysis.
AB  - This research study defines critical thinking in nursing and examines the
      thinking processes revealed by 15 African American mothers who are caregivers to
      adult children with HIV. The purpose of this cultural analysis was to compare the
      mothers' decision-making processes with their critical-thinking processes. Their
      culture, heritage, faith, and value of family influenced caregivers in this
      study. Their testimony revealed the patterns of creating a different path of
      care, weaving together resources, choosing among negative alternatives, and
      selecting stories to tell. Mothers' decisions were based on complex and holistic
      knowledge of their situations and culture and could be termed multilogical, a
      type of thinking considered necessary for managing complex situations. Health
      providers can benefit from an understanding of these decision-making processes.

PMID- 11989035
TI  - Organ donation beliefs of African American women residing in a small southern
      community.
AB  - There is a widening gap between the supply of available human organs and the
      critical number needed for transplants in the United States. For African
      Americans, the waiting period is about twice that of non-African Americans.
      Contributing to this situation is that organ donation among African Americans is
      less frequent than that among the general population. The purpose of this study
      was to discover the culture care beliefs, meanings, and practices of selected
      African American women regarding organ donation. Using the ethnonursing research
      method, data were collected through lengthy community visits and in-depth
      interviews. Two cultural and social structure dimensions, kinship ties and
      religion, were discovered to be most influential for these African American
      women. This study focused on the significance these dimensions play in the
      decision to donate an organ. Cultural care modalities for the provision of
      culturally congruent care were developed based on these findings.

PMID- 11989036
TI  - Culturally congruent end-of-life care for Jewish patients and their families.
AB  - This qualitative study was conducted to determine cultural influences in end-of
      life care among Jewish people. The conceptual framework for this study was drawn
      from Leininger's culture care theory. Informants consisted of 16 professional
      caregivers, family members, and rabbis who had experience with end-of-life care
      for Jewish patients. Interviews using open-ended and focused questions were used
      to gather informants' descriptions of their generic values, beliefs, and
      practices. Findings revealed the strong influence of religious, cultural, and
      historical factors in caring. Sanctity of life and life promotion are central to
      Judaism. Caring is a communal obligation that unites the family and community
      into a cohesive unit. Attitudes toward death are influenced by beliefs about
      afterlife and suffering. The value put on expert knowledge influences patients'
      and family members' expectations of professional caregivers. Similarities and
      differences were noted among different groups of informants.

PMID- 11989037
TI  - Teaching culturally competent care: nursing students experience rural Appalachia.
AB  - This article describes two courses, Health in Rural Appalachia and Clinical
      Practice in Appalachia, developed by one of the authors to increase students'
      cultural competence as professional nurses. Characteristics of the Appalachian
      culture are described as well as the need for cultural awareness and sensitivity
      in those providing health care. Both the three-credit seminar course and the one
      credit clinical course are described. Students' comments, from journals and other
      assignments, are interspersed throughout to illustrate various aspects of the
      cultural heritage they experienced as they worked with nurses and patients in
      eastern Kentucky.

PMID- 11989038
TI  - Culturally sensitive care of the Muslim patient.
AB  - The number of Muslims in the United States is growing. This article outlines a
      few of the major beliefs in Islam. Religious and philosophical factors that
      affect health care are discussed, and practical suggestions are made for nursing
      actions that lead to culture care preservation, culture care accommodation, and
      culture care restructuring. Major topics covered include the need for
      cleanliness, preparation for prayer, modesty, family structure, fasting and diet,
      and care of the dying.

PMID- 11989039
TI  - Partnering with a sister city organization for an international service-learning
      experience.
AB  - A partnership was established between Indiana University School of Nursing in
      Indianapolis and the Bloomington, Indiana-Posoltega, Nicaragua Sister City
      International organization to provide an international service-learning course in
      nursing. The course evolved over 4 years from an independent study for a single
      student to an elective course taken by 10 students. Student-learning activities
      included the following: developing relationships with community residents,
      providing prenatal classes, supporting nursing scholarships, and participating as
      interdisciplinary, multicultural team members. Partnering with our local Sister
      City International organization provided a rich opportunity for nursing students
      to learn about and participate with Nicaraguan and international health care
      workers in meeting population health needs in stable and refugee environments.

PMID- 11989040
TI  - Founder's focus: certification of transcultural nurses for quality and safe
      consumer care.

PMID- 11989041
TI  - Ropivacaine still has CNS toxicity: should local anesthetics be reevaluated?

PMID- 11989043
TI  - Evaluation of airway leakage using reinforced laryngeal mask during dental
      anesthesia with spontaneous breathing.
AB  - BACKGROUND: The purpose of this study was to evaluate whether manipulation or
      position change of the head during dental procedures for handicapped patients
      (mentally retarded) using a reinforced laryngeal mask airway for ventilation
      would lead to air leak. METHODS: All patients had a reinforced laryngeal mask
      airway inserted after induction of anesthesia; anesthesia was maintained with
      sevoflurane. Normal saline stained with methylene blue was instilled into the
      oral cavity of the patient. Then, the patient's laryngeal region was checked for
      blue staining with a fiberoptic bronchoscope. After dental treatment, the
      laryngeal region was checked again under fiberoptic bronchoscopy. The staining
      results were recorded and analyzed. RESULTS: In one of 51 patients (1.96%), the
      laryngeal region was stained blue after the flexible laryngeal mask airway was
      inserted. In ten of 51 (19.6%) patients, the laryngeal area was stained blue
      after the dental procedure. One of the ten patients who had a leak because the
      laryngeal mask was pulled out during the dental procedure. And in another one
      patient endotracheal tube was placed in lieu of laryngeal mask due to severe
      leakage. No oxygen desaturation below 90% occurred in all patients. No major
      complications such as fever or aspiration pneumonia were reported. CONCLUSIONS:
      The use of a reinforced laryngeal mask airway eliminates the complications due to
      endotracheal intubation and enhances the progress of the dental procedure.
      Although leakage may happen during dental manipulation, it usually does not raise
      serious problem. No serious complications such as aspiration were found in our
      cases. So a reinforced laryngeal mask airway may be considered to be another safe
      choice for maintenance of a patent airway in handicapped patients during dental
      procedures.

PMID- 11989042
TI  - A comparative study of the safety and efficacy of 0.5% levobupivacaine and 0.5%
      bupivacaine for epidural anesthesia in subjects undergoing elective caesarean
      section.
AB  - BACKGROUND: Levobupivacaine is the S(-)-enantiomer of the racemic bupivacaine.
      Data of pharmacological studies suggest that levobupivacaine has a lower
      potential of toxicity for central nervous and cardiovascular systems than does
      bupivacaine. The present study was undertaken to compare the safety and efficacy
      between levobupivacaine and bupivacaine in epidural anesthesia for Cesarean
      delivery. METHODS: A prospective, controlled, double-blinded study was conducted
      in 45 ASA class I-II Taiwanese obstetric patients undergoing elective Caesarean
      Section under extradural anesthesia. Patients were randomized to receive either
      25 ml of 0.5% bupivacaine or 0.5% levobupivacaine in a double-blinded fashion.
      The end points of measurements relevant to efficacy included onset, fade-out, and
      quality of anesthesia. The safety end-point measurements included Apgar scores,
      maternal ECG, maternal and neonatal blood pH, and adverse events. RESULTS: There
      was no significant difference between groups in the profile of sensory and motor
      blockade produced. Comparison of visual analogue pain scores did not show
      significant differences between groups at the corresponding times. There were no
      significant differences between groups in muscle relaxation scores assessed by
      obstetricians as well as the overall assessment of block quality rated by
      anesthesiologists. Apgar scores, maternal and neonatal blood pH, maternal ECG,
      and adverse events did not differ between groups. The drug-related adverse events
      were hypotension and shivering which were equally seen in levobupivacaine and
      bupivacaine groups. There was no other serious adverse event that happened in
      both groups. CONCLUSIONS: The onset and fade-out of sensory and motor blockade,
      quality of anesthesia, muscle relaxation and overall quality of anesthesia as
      assessed were comparable between two groups. No significant maternal or neonatal
      adverse events were found between the treatment groups. In comparison,
      levobupivacaine had the efficacy and safety profile equivalent to bupivacaine in
      epidural anesthesia for Caesarean section.

PMID- 11989044
TI  - Estimation of the depth of left-sided double-lumen endobronchial tube placement
      using preoperative chest radiographs.
AB  - BACKGROUND: Accurate placement of the double-lumen endobronchial tube (DLETs) is
      essential for optimal gas exchange during one-lung ventilation. The present study
      was designed to estimate the insertion depth of left-sided DLET using a
      preoperative chest radiograph. METHODS: Forty-five patients who underwent
      thoracic operations requiring intubation of a DLET were studied. The distance
      between the cephalic edge of the sixth cervical vertebra and the carina of the
      trachea (Dc-c) was measured from the anterior-posterior view of preoperative
      chest radiograph. After the tube was positioned in the main bronchus, a
      fiberoptic bronchoscope was introduced into the tracheal lumen to ensure the
      appropriate position of the DLET. Simple regression analysis for the insertion
      depth of the DLETs and Dc-c was performed. RESULTS: There was a highly
      significant correlation between the insertion depth of the DLET and both the Dc-c
      (y = 0.5304x + 19.646) and the body height (y = 0.1022x + 10.525), with P < 0.001
      and P < 0.01, respectively. CONCLUSIONS: To get the distance from the cephalic
      edge of the 6th cervical vertebra to the Dc-c from the chest radiograph
      preoperatively would be helpful for the evaluation of the proper insertion depth
      of the placement of DLET.

PMID- 11989045
TI  - Blood pressure measurement by pulse oxymetric method and comparison with
      conventional technique.
AB  - BACKGROUND: Measurement of systolic arterial blood pressure using a pulse
      oxymeter involves the evaluation of plethysmographic waveform during inflation
      and/or deflation of a blood pressure cuff. The purpose of this study was to
      determine that during slow inflation and deflation of cuff, which one of the
      pulse oxymetry-based readings of blood pressure is in best agreement with the
      value obtained by conventional method. METHODS: Blood pressure was measured in a
      sample of 50 healthy adult volunteers with conventional and pulse oxymetric
      methods. The degree of agreement between two methods was calculated. RESULTS: The
      mean difference between systolic blood pressure and pulse oximetric blood
      pressure during inflation of the cuff was 0.06 +/- 1.75 mmHg which was not
      different from zero. The highest correlation was also between these two pressures
      (0.988). CONCLUSIONS: This study shows that the best agreement is between
      systolic blood pressure and pulse oxymetric blood pressure during inflation. We
      conclude that for accurate measurement of blood pressure by pulse oxymetric
      method it is necessary to inflate the blood pressure cuff at a slow speed for the
      pulse oxymeter to have enough time to reach equilibrium state.

PMID- 11989046
TI  - Anesthetic considerations in intracranial aneurysm surgery.
AB  - Rupture of an intracranial aneurysm generally has a poor outcome, though
      perioperative treatments have improved. At the present time, the important
      factors in the management of intracranial aneurysm surgery appear to be the
      maintenance of adequate cerebral perfusion pressure and the avoidance of
      hyperglycemia. Relevant features of the anesthetic management of this surgery are
      discussed.

PMID- 11989047
TI  - Myofascial pain syndrome induced by malpositioning during surgery--a case report.
AB  - It is a real challenge to the anesthesiologists to differentiate brachial plexus
      injury (BPI) from myofascial pain syndrome (MPS). The possibility of MPS should
      be suspected in a patient with complaints of pain and dysfunction of the upper
      arm immediately after surgery. Here we report a case of gallstone with cervical
      ankylosing spondylitis who sustained myofascial pain syndrome (MPS) immediately
      after open cholecystectomy. We utilized dry needle stimulation to deactivate the
      trigger point of the pectoris minor muscle and stretching the muscle to relieve
      the muscle pain after the diagnosis was made. The patient completely recovered 2
      weeks later.

PMID- 11989048
TI  - Ropivacaine-induced convulsion immediately after epidural administration--a case
      report.
AB  - Ropivacaine is a new long-acting amide-type local anesthetic with less toxic
      effects compared with bupivacaine. Here, we report a case who sustained
      convulsion immediately after administration of epidural ropivacaine. A 75-year
      old woman was scheduled for total knee replacement. Epidural catheter was
      inserted smoothly. After aspiration test and injection of a test dose of 3 ml of
      2% lidocaine containing 15 micrograms epinephrine, 160 mg ropivacaine was
      administered epidurally. Unfortunately, a generalized tonic-clonic convulsion of
      sudden onset occurred right after ropivacaine injection. After he was given 100%
      oxygen and intravenous thiopental 150 mg, the patient recovered uneventfully.
      During the episode of convulsion sinus tachycardia at a rate of 120 beats/min
      without the interposal of other form of cardiac arrhythmia was noted, and
      respiration remained intact. This suggests that ropivacaine offers a good
      cardiovascular stability. This example serves as another evidence to remind us
      that even with a negative aspiration following epidural catheter placement and an
      uneventful test dose injection, inadvertent intravascular injection may still
      happen, particularly in the elderly.

PMID- 11989049
TI  - Fires of endotracheal tubes of three different materials during carbon dioxide
      laser surgery.
AB  - The hazards of fire during CO2 laser surgery of the airway necessitate the use of
      special endotracheal tubes. We reviewed 227 cases receiving CO2 laser laryngeal
      surgery over the past 7 years, of whom 3 suffered the complications as a result
      of endotracheal fire. Tracheal tubes made of different materials were used among
      them, including silicone T-tube (Montgomery Safe-T-tube), jet ventilation tube
      and Xomed laser shield endotracheal tube. In addition, we tested in vitro the
      combustibility of endotracheal tubes of six different materials which included
      silicone T-tube, jet ventilation tube, Xomed laser shield endotracheal tube,
      stainless Laser-Flex tracheal tube, polyvinyl chloride (PVC) endotracheal tube
      and aluminum foil wrapped PVC endotracheal tube by exposing them to continuous
      operating CO2 laser in room air. The time to initiation of fire and burn through
      the lumen was 0.3 second for T-tube, 0.5 s for jet ventilation tube, 5 s for
      Xomed laser shield endotracheal tube, and 0.8 s for PVC endotracheal tube,
      respectively. The Laser-Flex tracheal tube (stainless) and aluminum foil wrapped
      PVC endotracheal tube did not catch fire after 30 s of CO2 laser irradiation. The
      silicone T-tube seemed to be the most dangerous. Jet ventilation tube and Xomed
      laser shield endotracheal tube have the risk of fire. Aluminum foil wrapped PVC
      endotracheal tube was reported to catch fire before. Therefore we are of the
      opinion that the stainless endotracheal tube is the safest tube during CO2 laser
      surgery.

PMID- 11989050
TI  - Effects of intravenous ketorolac and fentanyl combined with midazolam on
      analgesia and side effects during extracorporeal shock wave lithotripsy.
AB  - BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is usually carried out
      on ambulatory or outpatient basis, and thus an appropriate anesthesia with
      minimal side effects is required. This study was to compare the analgesic and
      side effects of intravenous ketorolac with that of intravenous fentanyl, in
      combination with midazolam in ESWL. METHODS: Sixty patients were randomly divided
      into two groups; group K (n = 30) received 60 mg ketorolac i.v. 30 min before
      ESWL and group F (n = 30) received 100 micrograms fentanyl i.v. 3 min before
      ESWL. All patients received 2.5 mg midazolam i.v. 3 min before ESWL for
      intraoperative sedation. The pain intensity was evaluated by a numeric rating
      scale (NRS). A supplemental analgesia with intravenous fentanyl 25 micrograms was
      given when inadequate analgesia occurred (NRS > 3). Oxygen supplement through a
      face mask was given when the SpO2 fell below 94%. Side effects (nausea, vomiting,
      dizziness) and the time of discharge from post-anesthesia room (PAR) were
      recorded. The criterion of discharge from PAR was absence of any discomfort
      especially when the patient held upright. RESULTS: There was no difference
      between two groups in the demographic data, number of shock waves, duration of
      ESWL procedure, and fentanyl supplement. The incidence of oxygen supplement was
      lower in ketorolac group (1/30) compared with that of fentanyl group (20/30), P <
      0.01. The frequency of dizziness was lower in ketorolac group (1/30) than that in
      fentanyl group (25/30), P < 0.01. Three patients in fentanyl group complained of
      nausea, but none did in ketorolac group. The discharge time from PAR was
      significantly shorter in ketorolac group (14.7 +/- 8.4 min) than that in fentanyl
      group (49.5 +/- 14.6 min), P < 0.01. CONCLUSIONS: Both intravenous ketorolac and
      fentanyl in combination with midazolam could provide good anesthesia for ESWL.
      However, ketorolac plus midazolam had less side effects and allowed shorter
      discharge time from PAR. We suggest that intravenous ketorolac combined with
      midazolam is a safe and effective anesthetic regiment for ESWL, particularly on
      ambulatory basis.

PMID- 11989051
TI  - [The metabolic syndrome and exercise].

PMID- 11989052
TI  - [Is type 2 diabetes an old man's disease?].

PMID- 11989053
TI  - [Etiology and physiopathology in insulin resistance and type 2 diabetes--results
      of twin studies].
AB  - Twin studies have provided important insights into a complicated interplay
      between genetic and both prenatal and postnatal environmental factors implicated
      in the aetiology and pathophysiology of Type 2 diabetes. Although our present
      knowledge is too insufficient to discard the results of classical twin studies
      into the relative roles of genes versus environment for the development of
      diabetes and its metabolic defects, it is nevertheless clear that the classical
      twin model has been challenged by the thrifty phenotype hypothesis and its
      implications of an adverse intrauterine environment for the development of
      diseases in man, including diabetes. However, twins with their special
      intrauterine conditions may represent a helpful tool in the continual search for
      the mechanisms, and the extent to which early environment may play a role in the
      development of Type 2-diabetes and its various defects of glucose homoeostasis,
      including insulin resistance. In addition, twin studies have proved instrumental
      in molecular biology studies of genotype-phenotype associations and of muscle
      gene expression patterns in Type 2-diabetes and/or insulin resistance.

PMID- 11989054
TI  - [Insulin resistance: organ manifestations and cellular mechanisms].
AB  - Insulin resistance is an important issue in the understanding of the metabolic
      syndrome. Clinical insulin resistance is usually defined by reduced insulin
      mediated uptake of glucose in skeletal muscle. However, new studies have shown
      that liver and fat cells may also develop insulin resistance in subjects with the
      metabolic syndrome, specifically when these subjects are hyperglycaemic. New
      investigations also indicate that the endothelial cell itself can be insulin
      resistant, reduced blood flow and increased peripheral resistance as the outcome.
      Insulin resistance may not only induce hyperglycaemia, but also dyslipidaemia
      (increased plasma levels of free fatty acids and triglyceride, and reduced plasma
      HDL levels) and arterial hypertension. All these variables may provoke
      arteriosclerosis and ischaemic heart disease. Specifically, abdominal adiposity
      seems to be responsible for insulin resistance in subjects with the metabolic
      syndrome. The mechanism could be intracellular accumulation of acyl CoA and
      triglyceride. However, an increased production of peptides from the adipose
      tissue, such as TNF alpha and reduced production of adiponectine may also play a
      role. The mechanism by which FFA and triglyceride, together with the peptides
      mentioned, may induce insulin resistance at a cellular level, resulting in
      reduced glucose transport and intracellular glucose processing, is still being
      discussed. A change in the insulin signalling cascade is one possibility, but the
      results so far have been contradictory. Another possibility is, of course, that
      the cellular accumulation of acyl CoA itself intervenes with gene expression and
      with phosphorylation of proteins.

PMID- 11989055
TI  - [Screening and intervention. A strategy in type 2 diabetes?].
AB  - Before the introduction of screening for type 2 diabetes, it is necessary to
      evaluate not only the technology, but also the patient perspective, the
      economical consequences, and the organising aspects. A review of the relevant
      literature shows that type 2 diabetes is a rapidly increasing, serious disease.
      However, there is no documentation that systematic screening will have a positive
      effect on morbidity and mortality, owing to the lack of randomised clinical
      trials. The methods for screening could be optimised, and there is a lack of
      literature on patient perspective. Economical models indicate that opportunistic
      screening is more cost-effective than is systematic screening, but the lack of
      randomised trials makes the conclusion dubious. A decision to introduce
      systematic screening for type 2 diabetes should await the results of ongoing
      randomised clinical trials. In the meantime, efforts should be spent on improving
      the level of care for those already diagnosed with diabetes.

PMID- 11989056
TI  - [Life style counseling--what can be done in general practice?].

PMID- 11989057
TI  - [Endothelial dysfunction in metabolic syndrome and the significance of exercise].

PMID- 11989058
TI  - [Pregnancy in women with type 2 diabetes].

PMID- 11989059
TI  - [Physical training in the treatment of metabolic syndrome].
AB  - Increased daily physical activity is effective in the prevention of type 2
      diabetes and several of the components in the metabolic syndrome. However,
      dedicated efforts in exercise training will also be effective in the treatment of
      the metabolic syndrome. The effect on glycaemic control is of the same order of
      magnitude as can be achieved by oral antidiabetic drugs. In addition, exercise
      (endurance and/or strength training) will also improve insulin resistance and
      body composition. The results are more doubtful for the dyslipidaemia and
      hypertension, but if the training is combined with an appropriate diet, these
      abnormalities are also correctable.

PMID- 11989060
TI  - [Insulin resistance and muscle fibers].

PMID- 11989061
TI  - [Metabolic fitness: physical activity and health].
AB  - Physical inactivity is strongly associated with an increased risk of premature
      disease and death, and the falling level of physical activity in Denmark (as in
      many other countries) makes physical inactivity a major life-style risk factor in
      many western countries today. Both aerobic fitness (maximum oxygen uptake) and
      metabolic capacity of the muscles are important in this matter. The present paper
      focuses on the role of the metabolic capacity/fitness of muscle, because this
      appears to be especially critical for the development of metabolic-related
      diseases and thus for the health of the individual. A definition of metabolic
      fitness is proposed as the ratio between mitochondrial capacity for substrate
      utilisation and maximum oxygen uptake of the muscle. Indirect means of
      determining this parameter are discussed. Skeletal muscle is an extraordinarily
      plastic tissue and metabolic capacity/fitness changes quickly when the level of
      physical activity is altered. High metabolic fitness includes an elevated use of
      fat at rest and during exercise. The capacity for glucose metabolism is also
      enhanced in trained muscle. Some of these adaptations to physical activity are
      explained. Exercise-induced activation of genes coding for proteins involved in
      metabolism is described as an underlying mechanism for some of these adaptations.
      The increased gene expression is of relatively short duration, which implies that
      a certain regularity of physical activity is required to maintain high metabolic
      fitness. Thus, metabolic fitness is directly related to how much the muscle is
      used, but even low levels of physical activity have a beneficial effect on
      metabolic fitness and the overall health of the individual.

PMID- 11989062
TI  - [Chasing the genetic determinants of the presumed polygenic forms of type 2
      diabetes. Status and perspectives].

PMID- 11989063
TI  - [Cytokines in internal medicine--relation to insulin resistance and exercise].

PMID- 11989064
TI  - [Fatty tissue and insulin resistance: resistin and adiponectin].

PMID- 11989065
TI  - [Mammographic screening in the municipality of Copenhagen].

PMID- 11989066
TI  - [Use blood pressure determination].

PMID- 11989067
TI  - Anesthesia systems.
AB  - Anesthesia systems are used to induce general anesthesia during surgery. In
      addition, the systems track anesthetic agent and gas concentrations, as well as
      the patient's condition, using physiologic and multigas monitors. For this Update
      Evaluation, we present our findings for four newly evaluated models from two
      manufacturers and summarize our findings for the two previously evaluated models
      that are still on the market. (Our earlier Evaluations were published in the May
      June 1996 and January 1998 issues of Health Devices.) As in the previous
      Evaluations, our ratings are based largely on the degree of system integration,
      the suitability of the systems for various types of procedures, and cost. When
      equipped with the appropriate monitors, all the systems can deliver anesthesia
      effectively and can meet the minimum monitoring requirements of general surgery.
      While no system met all our criteria, any limitations of the systems can easily
      be overcome by the purchaser. We rate two models Preferred. One provides
      performance and features similar to the other evaluated systems at a
      significantly lower cost. The second offers exceptional flexibility in meeting
      monitoring requirements. Three models are rated Acceptable, and the remaining
      model is rated Acceptable (with Conditions). It is Acceptable only if it is
      equipped to supply air as an inspired gas.

PMID- 11989068
TI  - Depth-of-anesthesia monitoring. Should you invest in it?

PMID- 11989069
TI  - Siemens Servo 300 ventilators: potentially dangerous failures can be avoided by
      following specified maintenance procedures.

PMID- 11989070
TI  - Improper cleaning leads to premature failure of Nellcor reusable pulse oximeter
      sensors.

PMID- 11989071
TI  - Avoiding general-purpose infusion pumps that lack free-flow protection.

PMID- 11989072
TI  - [Digestive functional disorders: a problem exclusively affecting Western
      societies?].

PMID- 11989074
TI  - [Pulmonary histiocytosis X. Report of a case and review of the literature].
AB  - Histiocytosis X or Langerhans cell histiocytosis is an infrequent disease, which
      consists on proliferation of Langerhans cells. The etiology is unknown. Diagnosis
      is reached by electron microscope study of the biopsy, in which the Birbeck
      intracytoplasmatic granules of the Langerhans cells are found and/or by
      immunohistochemistry procedures able to detect S-100 antigen and CD1 cells.
      Diagnosis can also be reached with a bronchoalveolar lavage in which CD1 cells
      will appear in a score higher than 5%. We present the case of a 16 year-old girl
      that first appeared with a pulmonary lesion with a honey comb X-ray pattern and
      unsyntomatic mandibular bone affectation. Diagnosis was reached by biopsy study
      using S-100 antigen detection procedures. We consider this case an important one
      due to the infrequency of this particular disease.

PMID- 11989073
TI  - [Significance of the follow-up of patients with ischemic cardiopathy in the
      treatment with atorvastatin as secondary prevention. Pilot study].
AB  - OBJECTIVE: To determine the usefulness of different intensities of follow up when
      atorvastatin is used in the secondary prevention of ischemic heart disease.
      MATERIAL AND METHODS: Design. Prospective study with balanced randomized
      allocation including a concurrent control group. SETTING: Ambulatory care.
      PATIENTS: 75 patients hospitalized because of acute coronary syndromes were
      administered atorvastatin as secondary prevention of ischemic heart disease and
      randomized either to intensive follow up or to a control visit 6 months apart.
      INTERVENTIONS: The intensive follow up group (40 patients) was controlled every 2
      months as outpatients and a physical examine and lipid profile was done,
      enhancing diet and exercise and adjusting the statin dose. The control group was
      evaluated just once after a 6 six month period. RESULTS: 88% were males and the
      average age was 63.7 +/- 10 year. Basal characteristics, myocardial infarction,
      revascularized procedures and initial chemistry and lipid profile were similar in
      both groups, although there was a higher proportion of patients in the control
      group taking ACE. After 6 months total cholesterol, LDL cholesterol and
      triglycerides reduction was higher in the intensive follow up group (33 vs. 24,
      34 vs. 26 y 51 vs. 24 mg/dl, respectively) without realising statistical
      significance. Hospital readmissions were lesser in the intensive group (7.3% vs.
      19.4%, P = 0.114). There was one death in each group. CONCLUSIONS: Results show a
      tendency indicating that follow up planification is relevant to obtain the target
      lipid level recommended in the secondary prevention.

PMID- 11989075
TI  - [Acute adrenal insufficiency caused by bilateral adrenal hemorrhage as first
      manifestation of antiphospholipid syndrome. Report of a case and review].
AB  - Although adrenal hemorrhage is an unusual feature of antiphospholipid syndrome
      (APS), it can be its first clinical manifestation. The pathogenetic substratum is
      the thrombosis of the adrenal veins leading to hemorrhagic infarction.
      Recurrences are frequent in patients with APS-related thrombosis, thus long-term
      anticoagulation is advocated by most authors.

PMID- 11989076
TI  - [Spontaneous peritonitis induced by Campylobacter spp in patients with liver
      cirrhosis. Report of 2 cases and review of the literature].
AB  - Campylobacter spp is not usual as the aetiology agent for spontaneous bacterial
      peritonitis. We report two cases of spontaneous peritonitis due to Campylobacter
      jejuni diagnosed in our hospital and review the literature trough MEDLINE data
      base. We found 13 cases of spontaneous peritonitis in which Campylobacter sp was
      isolated from ascitic fluid. The main characteristics of these cases were: the
      existence of an evolved alcoholic cirrhosis, a high positivity of blood cultures
      as well as a high relapse index and letality.

PMID- 11989077
TI  - [Epidermoid carcinoma on Zenker's diverticulum].
AB  - Carcinoma is a rare but recognized complication of pharyngoesophageal
      diverticulum. We report the case of a 49-year-old man operated for a Zenker's
      diverticulum with an epidermoid carcinoma arising in the diverticulum. Since
      carcinoma is an uncommon complication of this pathology, we review the literature
      and discuss the therapeutic options.

PMID- 11989078
TI  - [Gastrointestinal disorders in Guatemala and their relationship with parasitic
      infections].
AB  - BACKGROUND: To determine the frequency of symptoms suggestive of functional
      gastrointestinal disorders and their relation to parasite infections in a
      developing nation. MATERIAL AND METHODS: 174 consecutive patients was seen in a
      gastroenterology clinic in Solola (Guatemala). RESULTS: Symptoms suggestive of
      irritable bowel syndrome was diagnosed in 37 patients (21%), irritable bowel
      syndrome with dyspeptic syndrome in 26 (15%) and dyspeptic syndrome in 24 (14%).
      Forty-two patients (24%) had been diagnosed of parasitation in the past. Such
      patients had a higher risk of suffering symptoms suggestives with functional
      gastrointestinal disorder (OR 6,335 CI 95% 2.72-14-75). Fifty-nine patients (34%)
      were subjected to parasite examination in stools; of these, 13 proved positive.
      In this same group of patients the risk of functional gastrointestinal problems
      was likewise higher among the subjects with parasite infection (p < 0.05). In
      turn, 41 patients (49%) with symptoms suggestives of gastrointestinal functional
      disorders were or had previously been diagnosed of parasite infection.
      CONCLUSIONS: Symptoms suggestives of functional gastrointestinal disorders are
      frequent in developing regions and its was in relation to intestinal parasites.

PMID- 11989079
TI  - [Assessment of the role of doppler color ultrasonography and magnetic resonance
      angio-resonance in the diagnosis of Takayasu's arteritis].
AB  - Takayasu arteritis (TA) is a chronic inflammatory process of unknown etiology
      which affects the aorta and its main branches causing occlusion, stenosis or
      dilation of the vessels concerned. A case of TA in a young woman is presented,
      who underwent colour doppler duplex ultrasound image study and whose diagnosis
      was confirmed by magnetic nuclear angioresonance (MNAR). The role of these two
      explorations in the detection and follow-up of this condition is discussed. Due
      to the fact that the expression and age at presentation may vary according to the
      different geographical areas affected, we would especially underline the new
      diagnostic criteria for this entity and based on the angiography findings
      obtained.

PMID- 11989080
TI  - [Sepsis and septic shock: a turmoil of inflammatory mediators with difficult
      therapeutic management].
AB  - Sepsis and septic shock continue being a topic of enormous interest for their
      high frequency, and for not existing a decrease in the figures of mortality in
      spite of the new acquired knowledges relation with their physiopathology and the
      advances arisen in the diverse applied treatments. The purpose of the present
      study is to update the present notions in the specialized literature, trying to
      summarize the complex existent interaction among different mediators of double
      character: exogenous and endogenous, and to enunciate the possible causes for
      those that the novel treatments applied in the sepsis continue not to be very
      promising.

PMID- 11989081
TI  - [Infection as the source and driving force of autoimmune diseases].

PMID- 11989082
TI  - [Metabolic alkalosis in the borderlines of hypochloremia].

PMID- 11989083
TI  - [Malignant neuroleptic syndrome and hyponatremia associated with risperidone
      poisoning].

PMID- 11989084
TI  - [Brucella pericarditis].

PMID- 11989085
TI  - [Disseminated candidiasis with myocardial involvement].

PMID- 11989086
TI  - [Recurrent rheumatic fever following prosthetic valve replacement].

PMID- 11989087
TI  - [Multimicrobial endocarditis caused by Streptococcus salivarius and Pseudomonas
      stutzeri: good course after early surgery].

PMID- 11989088
TI  - [Disseminated intravascular coagulation as presentation form of prostatic
      adenocarcinoma].

PMID- 11989089
TI  - [Antineutrophil cytoplasmic antibodies (ANCA): clinico-pathologic correlations
      iin a series of 82 cases].
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) have been described in a
      great variety of diseases in addition to the ANCA-associated systemic vasculitis
      (Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss
      syndrome (CSS)) and the pauci-immune rapidly progressive glomerulonephritis
      (RPGN). The objective of this work is to describe the clinical-pathological
      diagnosis of a series of patients with ANCA. MATERIAL AND METHODS: Retrospective
      review of patients with positive ANCA by indirect immunofluorescence in our
      hospital between January 1997 and December 1998. RESULTS: We identify 82 patients
      with ANCA. Six cases (7.3%) showed a C-ANCA pattern, 19 (23.2%) a P-ANCA pattern
      and 57 (69.5%) an atypical pattern. Eight patients (9.7%) had an ANCA-associated
      systemic vasculitis (5 WG, 2 MPA and 1 SCS). Four patients (4.9%) had a pauci
      immune RPGN without systemic vasculitis. One only case (1.2%) in our series
      presented a C-ANCA pattern without evidence of an ANCA-associated systemic
      vasculitis or a pauci-immune RPGN. CONCLUSIONS: The atypical pattern is the most
      frequent in patients with ANCA. A minority of patients with ANCA have an ANCA
      associated systemic vasculitis (WG, MPA or SCS) or a pauci-immune RPGN. The
      occurrence of a C-ANCA pattern is exceptional in patients without an ANCA
      associated systemic vasculitis or a pauci-immune RPGN.

PMID- 11989090
TI  - [Endocarditis caused by pacemaker lead].

PMID- 11989091
TI  - [Mycobacterium avium infection in a patient with AIDS].

PMID- 11989092
TI  - [Threatening hemoptysis in aortic aneurysm. Report of a case with prolonged
      survival].

PMID- 11989093
TI  - [Simultaneous diagnosis of chronic lymphocytic leukemia and polycythemia vera in
      a patient].

PMID- 11989094
TI  - [Donovanosis: increased incidence in our setting as a result of imported cases
      from endemic areas].

PMID- 11989095
TI  - [Merkel cell carcinoma of lymphatic node without evidence of skin tumor].

PMID- 11989096
TI  - [Epidemiology of bronchopulmonary tumors in a health area of Extremadura
      (southwest of Extremadura)].

PMID- 11989097
TI  - [Diagnosis of hemoptysis: is there a real argument?].

PMID- 11989098
TI  - [Usefulness of computerized tomography and bronchoscopy in patients with
      hemoptysis. Analysis of 482 cases].
AB  - OBJECTIVE: We have examined the computed chest tomography (CT) and bronchoscopy
      utility in diagnosis and accurately identifying the sites of pulmonary bleeding
      in patients with hemoptysis. METHODS: We prospectively reviewed the etiology and
      the site of bleeding of 482 patients with hemoptysis who had undergone
      bronchoscopy and CT when we suspected a carcinoma, bronchiectasis or the type of
      bleeding. We analyzed the age, sex, history of tobacco, bleeding, chest
      radiography, chest computed tomography and bronchoscopy. RESULTS: 62 years (DS
      13.6), 84.4% males, 80% smokers and a volume of bleeding of 42.5 ml/day (DS 89)
      for 15 days (DS 25). Lung cancer was identified in 43%, bronchiectasis in 20%,
      chronic obstructive lung disease in 14%, pneumonia 8% and an unknown etiology in
      only 3%. Bronchoscopy located the site of bleeding in 77% and CT in 83%. When we
      examine only the lung carcinomas, the chest radiography was normal in 11% and the
      bronchoscopy was diagnostic in 87%, including 6 cases with a normal CT.
      Simultaneously chest CT or radiography and bronchoscopy detected all the lung
      cancers. When the chest radiography was inespecific (32%), CT was diagnostic in
      43% and bronchoscopy in 14% (p < 0.001) or localized the site of bleeding in 52%
      with the CT or 23% with the bronchoscopy (< 0.001). CONCLUSIONS: We concluded
      that bronchoscopy and CT were useful and complementary in etiologic diagnosis and
      to localize the site of bleeding in patients with hemoptysis. The bronchoscopy
      was preferable in patients with a lung cancer and the CT when we studied all the
      etiologies or the patients without a lung cancer, especially when the radiography
      was normal. When we simultaneously used a CT or a radiography and the
      bronchoscopy, all the lung cancers were detected.

PMID- 11989099
TI  - [Pulmonary diffusion of carbon monoxide in patients with mitral stenosis].
AB  - OBJECTIVE: The aim of our work has been the study of CO diffusion capacity in
      mitral valve stenosis patients. METHOD: We have studied 15 control subjects and
      15 patients with mitral valve stenosis. We performed spirometry study and CO
      pulmonary diffusion tests (DLCO) by single breath method to determine two
      components: pulmonary capillary blood volume (Vc) and membrane diffusion factor
      (Dm). In addition, in mitral valve stenosis patients we performed a
      ecocardiography-doppler study. RESULTS: The mitral valve stenosis group had
      higher values of DLCO and Vc and a lower ratio of Dm/Vc than the control group.
      There is a negative correlation between Vc and the mitral valve area (r = -0.63;
      p = 0.037). We do not find any another correlation between the rest of
      ecocardiography doppler parameters and lung function test variables that we have
      measured. We have not found any differences between both groups in Dm.
      CONCLUSIONS: Mitral valve stenosis patients present a increase of CO pulmonary
      diffusion capacity and pulmonary capillary blood volume without changes in
      membrane diffusion factor.

PMID- 11989100
TI  - [Endoscopic treatment of pain in patients with chronic pancreatitis].
AB  - INTRODUCTION: Chronic Pancreatitis is a recurrent disease, frequently alcohol
      intake related and tend to occur in the third and the fourth decades. Stenoses
      and lithiasis in the main pancreatic duct causes obstruction and subsequently
      pain. Therefore endoscopic or surgical decompression of main pancreatic duct
      results in pain relief. SUBJECTS AND METHODS: Review our experience in the
      endoscopic management in patients suffering from chronic pancreatitis. 42
      patients underwent ERCP for management of their chronic pancreatitis. Therapeutic
      options were sphincterotomy alone, prostheses and "do nothing". Follow-up was
      made by phone call and outpatient office visits. Mean follow-up was 47.8 (27.2)
      months. RESULTS: 22 patients underwent therapeutic ERCP. In 8 patients we
      performed sphincterotomy and in 14 patients, a sphincterotomy and prostheses
      intubation. 8 patients are asymptomatic after a mean follow-up of 10.8 (11.6)
      months. 2 of them, underwent sphincterotomy and six of them, underwent
      sphincterotomy and prostheses intubation. CONCLUSION: Therapeutic ERCP is a tool
      that relieves pain in a fifth of patients suffering from chronic pancreatitis.

PMID- 11989101
TI  - [Anti-ribosomal antibodies as activity markers in systemic lupus erythematosus].
AB  - OBJECTIVES: a) to determine the prevalence of anti-ribosomal P antibodies in
      patients with ESL in our setting; b) to determine if there are associations
      between clinical signs of ESL and these autoantibodies; c) to analyze if there is
      any correlation between the presence of anti-P in patients with ESL and the
      results of other routine lab tests; and d) to assess the usefulness of
      implementing as routine test the determination of anti-P antibodies. MATERIAL AND
      METHODS: The study included 60 patients diagnosed of ESL and 61 healthy subjects
      as the control group. ELISA was used to determine anti-ribosomal antibodies. Chi
      square, Fisher and Student t tests were used for the statistical analyses.
      RESULTS: Of the 60 patients with SLE, 29 (48%) had anti-P antibodies as
      determined by ELISA. No association was observed between the presence of anti-P
      antibodies and psychosis, depression, hepatic failure, renal failure or any other
      clinical signs of ESL. A correlation was found between the levels of anti-P
      antibodies as determined by ELISA and anti-histone, ANA and AMA antibodies.
      CONCLUSIONS: The prevalence of anti-P antibodies was high among our ESL patients
      (48%). Their presence was not significantly associated with any clinical sign;
      however, an association was found with other lab markers related to the presence
      of active disease.

PMID- 11989102
TI  - [Hypokalemia-induced paraplegia secondary to acute diarrhea].
AB  - Hypokalemia can give a variety of syntomatology but more often courses without it
      or with inespecific clinical manifestations. In our enviroment the etiology of
      hypokalemia is wide but one of the most common causes in third world countries
      are diarrheas. We describe a case of severe hypokalemia due to acute diarrhea
      which was manifested with severe neurologic symtoms but improves with
      conventional treatment.

PMID- 11989103
TI  - [Acromegaly, multinodular toxic goiter and papillary carcinoma of the thyroid,
      potential role of G proteins].
AB  - It is well known that non-toxic goiter is not uncommon in acromegaly, but
      hyperthyroidism only occasionally occurs. In addition, the risk for the
      development of a malignant process is increased, the most often seen is carcinoma
      of the colon. Thyroid carcinoma is not frequent, nevertheless the rate in these
      patients is higher than general population. In this article, a case of
      hyperthyroidism, papillar carcinoma and acromegaly is presented. We reviewed the
      literature an discussed the possible pathogenesis.

PMID- 11989104
TI  - [Complication associated with celiac disease].
AB  - Enteropathy associated T cell lymphoma is the most serious complication of celiac
      sprue. The incidence of malignancy, in general, is approximately twofold greater
      in celiac disease than in the general population, but the risk of specific
      gastrointestinal malignancies is markedly increased. Lymphoma of the small
      intestine, comprises approximately 50% of the malignancies, and the most are of T
      cell origin. We report a case of celiac disease associated T-cell Lymphoma of the
      jejunum in a woman. At the age of 33 the diagnosis of Celiac sprue was made,
      after institution of a gluten free diet the patient improved, but, fifteen year
      later, the patient begin with fever and abdominal pain. Laparotomy showed a
      perforation of the intestine by a tumour.

PMID- 11989105
TI  - [Rhabdomyolysis syndrome and hyperthermia secondary to cocaine and/or ecstasy
      consumption. Report of 2 new cases and review of the problem].
AB  - We describe two cases of hyperthermia and rhabdomyolysis related to cocaine
      and/or ecstasy consumption. The clinical and laboratory findings are
      characteristic of hyperthermia syndrome in both cases. The first patient consumed
      cocaine, ecstasy and alcohol and afterwards suffers from hyperthermia and
      rhabdomyolysis associated with decreased conscious level, labile blood pressure,
      severe renal insufficiency (needing hemodialysis) and important liver failure.
      The second patient consumed ecstasy and alcohol with intense physical activity
      and shows the same but moderate clinical picture rapidly responding to
      intravenous fluid therapy. The incidence of this drug-induced hyperthermia is low
      compared to the important use of these illicit drugs. Nevertheless its increasing
      consumption will lead physicians to attend more patients with this syndrome and
      other related complications. For this reason we have reviewed and up-dated this
      problematic subject.

PMID- 11989106
TI  - [Syphilis: current therapeutic perspectives].
AB  - Despite many years of study questions regarding the appropriate therapy for
      syphilis still remain. Alternatives to penicillin for the treatment of syphilis
      continue to be sought. This article examines the studies relating to syphilis
      treatment published during the last years and also the new treatment guidelines
      for every stage of this sexually transmitted disease.

PMID- 11989107
TI  - [Citrobacter freundii bacteremia: report of 2 cases].

PMID- 11989108
TI  - [Pleural effusion secondary to Mycobacterium fortuitum infection].

PMID- 11989109
TI  - [Cranial granulomatous hypertrophic pachymeningitis].

PMID- 11989110
TI  - [Ticlopidine-induced hepatitis. Report of a new case].

PMID- 11989111
TI  - Shared mental health care: a bibliography and overview.

PMID- 11989112
TI  - Electronic communications.

PMID- 11989114
TI  - Kaiser Permanente upgrade to reflect its new Web strategy.

PMID- 11989113
TI  - HIPAA compliance support via portals.

PMID- 11989115
TI  - Florida hospital embraces single sign-on.

PMID- 11989116
TI  - Success of dental implants in the geriatric patient.

PMID- 11989117
TI  - Facility profile. Imaging center optimizes patient experience. Westchester
      Medical Imaging Services, Hawthorne, N.Y.

PMID- 11989118
TI  - Waste watch. Managers are looking in many directions to find the right disposal
      equipment.

PMID- 11989119
TI  - Market-driven department benchmarks.

PMID- 11989120
TI  - What's taking so long? Facilities managers and department heads take an
      incremental approach to e-commerce.

PMID- 11989121
TI  - And stay out! Hospitals have plenty of choices when it comes to access control
      technologies.

PMID- 11989122
TI  - Maximum uptime. JCAHO's medical device maintenance standards favor flexibility.

PMID- 11989123
TI  - 'Homey' touches, special care. Design trends offer cleaning and product selection
      challenges for ES managers.

PMID- 11989124
TI  - [Geriatrics at hospitals for acute diseases].
AB  - Almost half of adults who occupy hospital beds are > = 65 years; this proportion
      is expected to increase as the population ages. Hospitalization can magnify age
      related physiologic changes and increase morbidity. The outcome of
      hospitalization appears to be poorer with increasing age; outcome is better in
      patients hospitalized for elective procedures (e.g., joint replacement) than in
      those hospitalized for serious conditions (e.g., multisystem organ failure).
      About 75% of persons > = 75 who are functionally independent when admitted to
      hospitals from their homes are not functionally independent when discharged. Even
      when an illness is treatable or appears uncomplicated, patients may not return to
      prehospitalized functional status. A particularly successful model is Acute Care
      for the Elderly (ACE) intervention, a program of patient-centered care designed
      to prevent dysfunction. Hospitalization is necessary only when the patient cannot
      receive appropriate treatment in any other environment. The health care
      practitioner should promptly identify patients who can benefit from medical care
      in another environment (e.g., at home). Acute hospital care should only be of
      sufficient duration to allow successful transition to home care, a skilled
      nursing facility, or an outpatient rehabilitation program.

PMID- 11989125
TI  - [Study of the mesenteric arteries with multislice spiral CT angiography].
AB  - The aim of our study was to optimize an high-resolution CT angiography protocol
      for the evaluation of mesenteric arteries using a multislice spiral CT equipment.
      A volumetric dataset was acquired during dynamic i.v. injection of non-ionic
      iodine contrast medium; images were subsequently reconstructed by means of a
      dedicated off-line workstation, equipped with volume-rendering software.
      Excellent depiction of the anatomy of mesenteric arteries and collateral vessels
      was obtained in all the cases. In conclusion, new multislice spiral CT scanners
      allow an optimal noninvasive evaluation of mesenteric arteries, possible up to
      now only with catheter angiography.

PMID- 11989126
TI  - [Chronic pain in the elderly].
AB  - Chronic pain is a common problem for the aged. Aim of the study was to evaluate
      prevalence, characteristics and influence on functional parameters of chronic
      pain in the elderly. Our study included 105 patients (mean age 82.2 +/- 9 yr).
      Chronic pain, tested by using the McGill Pain Questionnaire, was present in 87
      patients (82.9%); it lasted more than 2 years and it was continuous in half of
      them (49.4%). Our study shows that chronic pain in the elderly has a strong
      affective component. Its intensity, evaluated by specific tests such as
      analogical visual and verbal scales, influences old patient's quality of life.

PMID- 11989127
TI  - [Esophageal transit and esophageal motility disorders in patients with nontoxic
      goiter and recurrent dysphagia].
AB  - Esophageal motor function was studied in 14 patients affected with diffuse and
      (multi)nodular nontoxic goiter, with dysphagia and neck discomfort, and in 10 age
      matched controls without thyroid and/or gastroesophageal diseases. Esophageal
      manometry was employed to evaluate upper esophageal sphincter pressure (UESP) and
      lower esophageal sphincter pressure (LESP), amplitude, duration and propagation
      velocity of peristaltic contractions and the presence of simultaneous deglutitive
      pressure waves. Esophageal transit was evaluated by radioisotopical method, at
      different times, in proximal, middle and distal esophagus. LESP was significantly
      lower (p < 0.001) in goitrous patients compared with controls. No difference was,
      on the contrary, found in the UESP, esophageal peristaltic wave amplitude and
      duration. Significantly (p < 0.05) increased propagation velocity of the
      peristaltic contractions and the presence of simultaneous deglutitive pressure
      waves in distal esophagus were observed in goitrous patients. Esophageal transit
      delay was found early in proximal and middle, and, at all times, in distal part
      of the esophagus of nontoxic goitrous patients. It is concluded that esophageal
      transit delay, early in the upper and prolonged in the lower part of the
      esophagus, represents the main findings of the esophageal dysfunction in the
      patients with nontoxic goiter and dysphagia.

PMID- 11989128
TI  - [Assessment of anxiety levels in patients during diagnostic endoscopy].
AB  - Patients with increased pre-endoscopic anxiety take advantage of the use of
      conscious sedation. However, the habit of using premedication varies according to
      the type of endoscopic examination. Aims of this study were: to evaluate whether
      different endoscopic procedures may have different effects on patient anxiety;
      and whether anxiety affects patient tolerance. 163 consecutive outpatients
      undergoing endoscopy (75 gastroscopy, 51 colonoscopy and 37 bronchoscopy) were
      interviewed to evaluate pre-endoscopy anxiety, by using the Spielberger State
      Trait Anxiety Inventory. After endoscopy, endoscopists rated patient cooperation
      on a 10-cm visual analogue scale. Females had state and trait anxiety levels
      higher than males (50.49 +/- 1.37 vs 45.07 +/- 1.20, p < 0.01; and 44.46 +/- 1.06
      vs 38.48 +/- 1.01, p < 0.01). Anxiety levels were not related with the type of
      endoscopic procedure. A direct relationship was observed between state and trait
      anxiety (p < 0.001). Patient cooperation to endoscopy was inversely related with
      both trait (p < 0.05) and state anxiety (p < 0.01). In conclusion, gastroscopy,
      colonoscopy and bronchoscopy seem to induce similar pre-endoscopy anxiety levels.
      Therefore, the different frequency in the use of intravenous sedation between
      bronchial and gastrointestinal endoscopy does not seem justified.

PMID- 11989129
TI  - [A dangerous "risotto"].
AB  - We report an unusual digitalis poisoning case, with a positive result, caused by
      the swallowing of digitalis purpurea leaves. They were taken for borage leaves,
      usually used to prepare "risotto". Be careful not to eat vegetables you don't
      usually eat, because some of them may have different toxicity levels.

PMID- 11989130
TI  - [BK virus encephalitis in an HIV-seropositive patient. Preliminary data].
AB  - The BK virus (BKV) belongs to the family of the polyoma group. Although up to 60%
      of AIDS patients excrete BKV in the urine, there have been few reports of
      infection of kidney, lung, retina, brain and peripheral blood mononuclear cells.
      We report the case of a 37 year-old male HIV positive patient with BKV
      encephalitis. This diagnosis should be considered in AIDS patients with signs of
      cerebral disease.

PMID- 11989131
TI  - [Calmette-Guerin bacillus disseminated infection after intravesical
      instillation].
AB  - Local immunotherapy with bacillus Calmette-Guerin (BCG) is an effective and
      frequently used treatment for superficial bladder cancer. Serious side effects
      are infrequent but can affect every organ system. We describe a 53 year- old man
      with a disseminated bacillus Calmette-Guerin (BCG) infection after intravescical
      instillation for bladder carcinoma. Recent literature is reviewed for this rare
      complication.

PMID- 11989132
TI  - [Current knowledge on pathogenesis and pathologic anatomy of chronic obstructive
      pulmonary disease].
AB  - In smokers with chronic obstructive pulmonary disease (COPD), pathological
      changes can be found in the central airways, peripheral airways, lung parenchyma
      and pulmonary arteries. Interestingly, some of these changes can be already
      present in the lungs of smokers with normal lung function indicating that smoking
      itself is able to damage the lung even before airflow limitation occurs. The
      purpose of this paper is to describe the structural changes present in the lungs
      of smokers with normal lung function and those present in the lungs of smokers
      with COPD, in an attempt to underline the possible mechanisms contributing to
      airflow limitation in these patients. In addition we will review the few studies
      that described the structural changes that occur in severe COPD and those that
      occur during an exacerbation of the disease. Finally we will address the effect
      of smoking cessation or anti-inflammatory treatment in an attempt to investigate
      the potential reversibility of the pathologic lesions characteristic of COPD.

PMID- 11989133
TI  - [Coughing. Pathognomic significance and therapeutic options].
AB  - A wide range of disease processes may present with cough and definitive treatment
      depends on making an accurate diagnosis of the cause. Acute or short-lived cough,
      which most commonly occurs in association with viral upper respiratory tract
      infection, is of a little consequence, usually resolving in a matter of days. The
      most common chronic causes of cough are post-nasal drip, asthma, gastro
      esophageal reflux and chronic bronchitis. The different conditions that cause
      cough have in common the fact that are mediated by the vagus nerves, with sensory
      receptors in and under the epithelium from the larynx to the smaller bronchii.
      The receptors are polymodal, responding to a large variety of stimuli, including
      mechanical and chemical irritants, inflammatory mediators, intraluminal material
      and large volume changes of the lung. Intensive treatment of underlying cause
      usually leads to improvement or resolution of cough. However, in a minority of
      patients, no underlying cause is identified despite appropriate investigation: in
      these subjects or when cough interferes with patient's health or sleep is
      indicated a non specific treatment with antitussive therapy.

PMID- 11989134
TI  - [Hypercholesterolemia, cardiovascular risk, and hypocholesteremic treatment in
      the elderly].
AB  - The role of cholesterol as a cardiovascular risk factor in the elderly is not
      completely clear at the moment. Epidemiologic studies show a continuous relation
      between cholesterol levels and cardiovascular risk even in the elderly, in fact,
      in spite of a lower Relative Risk, they have a greater Absolute Risk and Absolute
      Benefit Increase. In patients over 75-80 years old cholesterol loses its role as
      a risk factor, probably because of comorbidity, typical in this period. Trials
      show the efficacy of hypocholesterolemic therapy with statins in secondary
      prevention in the elderly; fewer data are available for primary prevention.
      Therapeutic attitudes suggest a pharmacologic intervention of secondary
      prevention in young and old elderly to lower LDL-C levels, which are more closely
      related to the events. In primary prevention we should use drugs to reach a LDL-C
      level lower for each additional risk factor, until 75 years old; in the old
      elderly we should decide on drug therapy according to the biological age and
      expected lifespan. Statins seem to be the most effective and safest drugs to
      reach this aim.

PMID- 11989135
TI  - A lesson from travel: first aid is needed before medical knowledge in emergency
      elderly care.

PMID- 11989136
TI  - Travellers' thrombosis.
AB  - Anecdotal reports have suggested a link between flying and the development of
      blood clots. A recent prospective study looking at passengers before and after
      flying has demonstrated a much higher incidence of asymptomatic venous thrombosis
      than we expected. In the same paper, graduated elastic compression stockings
      reduced this incidence of asymptomatic venous thrombosis. Further studies are
      required to see how many passengers develop symptomatic deep vein thrombosis and
      to assess the overall incidence of venous thromboembolic disease. A major
      epidemiological study, an interventional study to assess the efficacy of
      mechanical methods of venous thrombosis prophylaxis and the effect of graduated
      compression stockings, and studies to look at the effect of the cabin environment
      on thromboembolism are planned.

PMID- 11989137
TI  - Sickness at high altitude: a literature review.
AB  - When some individuals spend just a few hours at low atmospheric pressure above
      1,500 m (5,000 ft)--such as when climbing a mountain or flying in a plane at high
      altitude--they become ill. Altitude sickness studies originally concentrated on
      life-threatening illnesses which beset determined and athletic climbers at
      extreme altitudes. In recent years, however, research attention is moving towards
      milder forms of sickness reported by a significant proportion of the growing
      number of visitors to mountain and ski resorts at more moderate altitude. Some of
      this research is also relevant in understanding the problems experienced by
      passengers in newer planes that fly at a significantly higher equivalent cabin
      altitude, i.e. 2,440 m (8,000 ft), than earlier designs. Engineering solutions-
      such as enriched oxygen in enclosed spaces at altitude, or in the case of
      aircraft, lower cabin altitudes--are possible, but for an economic assessment to
      be realistic an engineer needs to identify the scale of the problem and to
      understand the factors determining susceptibility. This review concentrates on
      the problems of mountain sickness in the ordinary population at altitudes of
      around 3,000 m (10,000 ft); this is a problem of growing concern as ski resorts
      develop, mountain trekking increases in popularity, and as higher altitude cabin
      pressures are achieved in aircraft.

PMID- 11989138
TI  - Tinnitus: an update.
AB  - Tinnitus is the perceived sensation of sound in the absence of acoustic
      stimulation. It is the commonest otological disorder referred to either the
      general practitioner or ear-nose-throat surgeon. This short review examines
      prevalence, aetiology, associated clinical symptoms, investigations and
      management. Despite current usage of a vast number of treatment modalities there
      remains no specific cure for the condition. However, there is currently great
      emphasis on tinnitus retraining therapy (TRT) in its management. The applications
      and results of TRT have, indeed, been encouraging--and are also briefly discussed
      here.

PMID- 11989139
TI  - Hemihypertrophy.
AB  - Hemihypertrophy refers to asymmetry of the body to a greater degree than can be
      attributed to normal variation. Most causes can be diagnosed from history and
      physical examination. Hemihypertrophy is cosmetically unsightly and the
      psychological impact can be quite prolonged. This article reviews the causes and
      differential diagnosis of hemihypertrophy and offers an approach to the
      management of this condition. Children with isolated hemihypertrophy are at
      increased risk for neoplasms. Periodic abdominal ultrasound examination and
      physical examination during infancy and childhood are recommended for early
      tumour detection.

PMID- 11989140
TI  - Oxidative stress, micronutrients, diabetes mellitus and its complications.
AB  - Oxidative stress is defined as excessive production of reactive oxygen species
      (ROS) in the presence of diminished antioxidant substances. It has been shown
      that oxidative stress has an adverse effect on glucose metabolism. Development of
      the disabling chronic complications of diabetes mellitus (DM) has also been
      attributed to oxidative stress. The body's defence against oxidative stress is
      accomplished by interconnecting systems of antioxidant micronutrients (vitamins
      and minerals) and enzymes. While the vitamins act as donors and acceptors of ROS,
      minerals regulate activity of the enzymes. This review article is focused on the
      preventive and therapeutic roles of these antioxidant micronutrients in DM.
      Although there is scarcity of data from controlled studies, anecdotal reports
      indicate that the use of certain antioxidant vitamin and mineral supplements may
      be beneficial as an adjunct therapy in the management of DM and its
      complications. In particular, it has been reported that high doses of single
      micronutrient antioxidant supplements, such as vitamin E, may be beneficial to
      patients suffering from this disease. However, micronutrient antioxidants
      interact with each other in a biochemical chain of defence against free radicals,
      and the use of high doses of a single antioxidant poses potential risks because
      it could perturb the antioxidant-prooxidant balance. It has, therefore, been
      recommended that high doses of micronutrient antioxidant vitamins should be
      administered in combination rather than as single supplements. There are a
      growing number of preparations containing mixtures of antioxidant vitamins and/or
      trace elements. A particularly impressive supplement is a new formula called
      Akesis, which is a mixture of antioxidant vitamins and antidiabetic trace
      elements, adequately balanced with other vitamins and minerals that enhance
      metabolic processes.

PMID- 11989141
TI  - Caring for a relative with chronic fatigue syndrome: difficulties, cognition and
      acceptance over time.
AB  - The present study explored the difficulties experienced by carers of chronic
      fatigue syndrome (CFS) sufferers, their cognitions, and their efforts to accept
      the illness. Semi-structured interviews were conducted with 17 carers to study
      these issues, retrospectively, over three stages: before the diagnosis of CFS,
      shortly after the diagnosis, and at present. Surprisingly, the results suggested
      that carers, several of them absent from home during the day, felt that their
      lives were only minimally constrained by the illness. Nevertheless, all carers
      reported specific coping efforts to manage both the illness and their own
      distress, and indicated that they learned to accept the illness over time.
      However, acceptance appeared to be a form of resignation rather than a positive
      appreciation of the illness. In light of the uncertainties surrounding the origin
      of CFS and carers' apparent confusion, the results obtained in the present study
      are significant in that they increase our understanding of CFS carers' quality of
      life, their efforts to cope with the illness, and the physical and emotional help
      they may provide to the sufferer. Such information can be usefully employed in
      the increasing development of counselling interventions and instrumental support
      networks that involve both sufferers and their carers.

PMID- 11989142
TI  - How do younger patients view long-term treatment with proton pump inhibitors?
AB  - Dyspepsia (also called indigestion or heartburn) is a common reason for
      consulting a general practitioner (GP). One of the medicines available for
      treating dyspepsia is a type of acid suppressant called a proton pump inhibitor
      or PPI. There is a growing concern over the rapid increase in prescribing PPI
      drugs and the escalating costs associated with this trend. There has been an
      effort to reduce prescribing of PPIs. Most patients who are prescribed these
      drugs are aged over 45 years. Younger patients (those under 45) are a minority
      but, in absolute terms, a sizeable number who could potentially be taking PPIs
      for many years and therefore be expensive. This is a group for whom the
      appropriateness of prescribing PPIs is often questioned because of the everyday
      and non-life threatening nature of gastric disorders. A widespread association
      between dyspeptic symptoms and features of adverse lifestyle that are, at least
      in principle, easily avoidable has led to the suggestion that PPIs might be used
      to support unhealthy lifestyles. The perspective of younger patients taking PPIs
      in the long term has been neglected. In this paper the accounts of ten younger
      respondents, from a large qualitative investigation of patient and GP
      perspectives on long-term PPI prescribing, are examined to gain insight into how
      younger patients viewed their stomach problem, the effectiveness of PPIs and long
      term PPI taking. The findings showed a gap between patient experience and medical
      perception. The perspectives of younger patients need to be recognised in order
      to deal adequately with their concerns about illness and treat their
      gastrointestinal conditions effectively.

PMID- 11989143
TI  - Who is responsible for specifying healthy travel conditions?

PMID- 11989144
TI  - Suggestions in maternal and child health for the National Technology Assessment
      Programme: a consideration of consumer and professional priorities.
AB  - In North Staffordshire, the Achieving Sustainable Quality in Maternity (ASQUAM)
      meetings provide the programme for clinical guidelines and audit over the
      following year. The ASQUAM clinical effectiveness programme has attempted to
      address a number of the issues identified as obstacles to informed democratic
      prioritization. For example, it became clear that a number of topics raised were
      actually research questions. The organizers therefore decided to split the fourth
      ASQUAM day into an 'audit' morning and a 'research' afternoon. The meeting
      organized by RJ, CR and PJ in partnership with the Midwives Information and
      Resource Service and the National Childbirth Trust, was timed to allow the
      research ideas to feed into the national Health Technology Assessment (HTA)
      programme. This meeting was designed to increase the profile of ASQUAM amongst
      consumers and to increase their representation at the meeting. Objectives were to
      choose a new set of research priorities for the year 2000, and to ascertain the
      voting pattern of comparison to health professionals. There was overall agreement
      in terms of priorities, with the consumer group prioritizing 8 of the 10 topics
      chosen by the professionals (or 10 of the 11). No significant differences between
      the proportions of voted cast for each topic by professionals and consumers were
      found apart from topic 20. The numbers of consumers were small which does limit
      the number the validity of statistical comparisons. Nevertheless, it is clear
      that voting patterns were similar. Overall the process suggests that democratic
      prioritization is a viable option and one that may become essential within the
      framework of clinical and research governance.

PMID- 11989145
TI  - A study of fetal anomalies detected by ultrasound in Bangladesh and their
      relative frequencies.
AB  - A total of 5,841 obstetric patients were scanned over a period of 34 months. This
      study was undertaken to establish the anomalies that can be detected by
      ultrasound and to find out their relative frequencies in Bangladesh. Of the 41
      cases of congenital anomalies, seven cases were of hydrocephalus, seven were of
      hydronephrosis, five were of mild hydrocele (which could be just a physiological
      variant), five of anencephalus, five of fetal ascites, three of omphalocele, two
      of small biparietal diameter (BPD), two of short-limb, and one each of
      gastroschisis, renal cyst, hepatosplenomegaly, pleural effusion with oedema
      (hydrops fetalis) and bradycardia with irregular fetal heart beats. The benefits
      of the procedure are that in some cases like hydronephrosis, early detection can
      lead to early treatment to save the kidney by removing the congenital obstruction
      soon after birth, and in hydrocephalus and anencephalus it will help in proper
      management. The problem was there was a chance of higher detection of
      hydrocephalus and anencephalus as these were clinically suspected by the
      obstetrician and referred for a scan.

PMID- 11989146
TI  - A comparison of two methods for detection of Chlamydia trachomatis in the male
      urethra.
AB  - Several methods have been put forward for screening people for Chlamydia
      trachomatis infection of the urogenital tract. It is often believed that culture
      is the gold standard. However, newer and faster methods are being developed. This
      study reports the result from the comparison of two methods.

PMID- 11989147
TI  - The risk of suffering from Legionnaires' disease whilst abroad.

PMID- 11989148
TI  - Bowel obstruction due to extrinsic compression by metastatic lobular carcinoma of
      the breast.
AB  - The commonest sites for breast cancer metastases are the bones, lungs, liver,
      pleura, adrenals and central nervous system. However, although other sites have
      been reported, solitary metastases to the gastrointestinal tract are extremely
      uncommon. Widely disseminated gastrointestinal metastases may be found in up to
      20% of patients. Although only 15% of patients with breast cancer will have the
      lobular variety, these make up the majority of patients with solitary
      gastrointestinal metastases. Here we present three cases where solitary lobular
      breast cancer metastases have been demonstrated to be the cause of bowel
      obstruction. In two cases of duodenal obstruction was demonstrated and in the
      third colonic obstruction. In all cases a focal extrinsic compression was found.

PMID- 11989149
TI  - Health and safety aspects of business travel.

PMID- 11989150
TI  - Managing jet lag.

PMID- 11989151
TI  - Health-wise, how far can we go forward? Or even backward?

PMID- 11989152
TI  - "Take my life, but spare my son's".

PMID- 11989153
TI  - Giving students a taste of medicine.

PMID- 11989154
TI  - My patients built me a practice.

PMID- 11989155
TI  - Why etiology matters.

PMID- 11989156
TI  - Demystifying the art of coding.

PMID- 11989157
TI  - When an insurer won't renew your policy.

PMID- 11989158
TI  - Low-level codes can bring in high revenue.

PMID- 11989159
TI  - EMRS cost too much? This group says no way!

PMID- 11989160
TI  - EMRs boost efficiency, too.

PMID- 11989161
TI  - How to win your case before it reaches court.

PMID- 11989162
TI  - Going solo: my leap of faith paid off.

PMID- 11989163
TI  - Our secret for saving time, money, and grief.

PMID- 11989164
TI  - Credit my wife with saving my patient.

PMID- 11989165
TI  - Put fun back in your practice.

PMID- 11989166
TI  - Roukema introduces scaled-down parity bill.

PMID- 11989167
TI  - Thompson, Daniels, Scully suggest Medicare hospital cuts.

PMID- 11989168
TI  - MedPAC officially releases payment system recommendations.

PMID- 11989169
TI  - Hospitals face new financial challenges.

PMID- 11989170
TI  - Hospitals, health care organizations launch HHS UPL lawsuit.

PMID- 11989171
TI  - Covering the uninsured: the challenge looms large.

PMID- 11989172
TI  - [Brain--inside and outside].

PMID- 11989173
TI  - [Functional imaging of neuroreceptors in parkinsonism].

PMID- 11989174
TI  - [HIV resistance testing. Introduction of a new technique].
AB  - Antiretroviral combination therapy is the standard of care in the treatment of
      HIV-infection in the industrialised world. Treatment with antiretroviral drugs
      provides selective pressure on HIV. Suboptimal anti-HIV treatment increases the
      risk of resistant mutations developing. Recently, genotypic and phenotypic
      resistance testing has become available for routine use. So far, few data have
      been published on the efficacy of this testing and there is no evidence of
      clinical benefit. The use of genotypic resistance testing should--until further
      evidence has been provided--be limited to patients with virological failure on a
      current regimen. Genotypic resistance testing can also be used for
      epidemiological surveillance.

PMID- 11989175
TI  - [The working brain--how does it look like?].
AB  - Numerous brain functions, such as awareness of surroundings, control of
      movements, thoughts, and memory have always been a kind of mystery, which has
      provoked human curiosity and thus inspired research in many areas. The present
      paper gives an overview on imaging research of the human brain's functions. The
      historical progress is briefly reviewed with the emphasis on major Danish
      contributions. The major methods of mapping brain functions and their biological
      basis are mentioned. These methods are positron emission tomography (PET) and
      functional magnetic resonance imaging (fMRI). They are highly technological and
      generate enormous amounts of data. Thus, data analysis will per se be a research
      area in brain imaging. Finally, several examples of the authors' results on
      functional activation are dealt with. These examples aim to illustrate the
      research area and its contribution to our increased knowledge of the working
      brain.

PMID- 11989176
TI  - [Electrocardiographic Q wave is of no significance after myocardial infarction].
AB  - A Q wave has high specificity in identifying acute myocardial infarction and is
      associated with infarcts of a larger size. A considerable number of studies have
      addressed the prognostic value of the presence of a Q wave in the
      electrocardiogram before and after the introduction of thrombolytic therapy.
      Overall, these studies have demonstrated that a Q wave has slight, or even no,
      prognostic impact, especially in studies performed since the introduction of
      thrombolytic therapy. Some therapeutic choices have been suggested according to
      the presence or absence of Q waves. These suggestions depend basically on
      subgroup analysis with different results and hence have not documented that a Q
      wave has any value in therapeutic choices. A pathological Q wave has no
      significant prognostic value after a myocardial infarction and there is very
      doubtful documentation that a Q wave has any value for therapeutic choice.

PMID- 11989177
TI  - [Quality control of ultrasound weight estimation in a central hospital].
AB  - INTRODUCTION: The aim of the study was to carry out a quality control of fetal
      weight estimated by ultrasonography in an obstetric ward of a district hospital.
      MATERIALS AND METHODS: The study comprised 105 scannings. The weight estimates
      were projected to the date of birth, and the difference in percentage between the
      actual birth weight and the projected weight was estimated. RESULTS: There was a
      good agreement between the projected weight and the actual birth weight (r =
      0.87). The mean value was -2.5%, and the standard deviation in the difference
      between the projected weight estimates and the actual birth weight, was 11%,
      which was consistent with findings in other studies. DISCUSSION: Ongoing quality
      control of weight estimates and establishment of obstetric databases are
      recommended.

PMID- 11989178
TI  - [Traffic-related air pollution at the place of residence and risk of cancer among
      children].
AB  - INTRODUCTION: The hypothesis that exposure to traffic-related air pollution
      increases the risk of cancer developing during childhood was investigated.
      MATERIALS AND METHODS: We enrolled 1,989 children notified to the Danish Cancer
      Registry with a diagnosis of leukaemia, tumour of the central nervous system
      (CNS), or malignant lymphoma during 1968-1991, and 5,506 control children
      selected at random from the entire childhood population. The residential
      histories of the children were traced from nine months before birth up to the
      time of diagnosis, as was a similar period for the controls. Information on
      traffic and the configuration of streets and buildings was collected for each of
      the 18,440 identified addresses. Concentrations of benzene and nitrogen dioxide
      (indicators of traffic-related air pollution) were calculated for the relevant
      residential periods, and combined into exposures to air pollution during
      pregnancy and childhood, respectively. RESULTS: The risks of leukaemia, CNS
      tumours, and all selected cancers combined were not related to exposure to
      benzene or nitrogen dioxide during either period. The risk of lymphomas increased
      by 25% (p for trend = 0.06) and 51% (p for trend = 0.05) for a doubling of the
      concentration of benzene and nitrogen dioxide, respectively, during the
      pregnancy. The association was restricted to Hodgkin's disease. DISCUSSION: On
      the basis of a low potential for selection bias, information bias, and
      confounding factors, we conclude that traffic-related air pollution at the
      residence of children is not linked to the risk of leukaemia or CNS tumour, which
      are the two major types of childhood cancer. The results indicated a possible
      association between air pollution and the risk of Hodgkin's disease, but the
      evidence allows of no firm conclusion at present.

PMID- 11989179
TI  - [Endovascular treatment of abdominal aortic aneurysms].
AB  - INTRODUCTION: The endovascular method of treating abdominal aortic aneurysms was
      introduced as an alternative to conventional surgical repair in the hope of
      reducing the operative mortality and morbidity. MATERIAL AND METHODS: Thirty
      patients were selected for endovascular aneurysm repair on the basis of
      anatomical criteria. The result of the treatment was evaluated by angiography on
      completion of surgery and by contrast-enhanced CT scans at 1, 3, 6, and 12
      months, and annually thereafter. RESULTS: Exclusion of the aneurysm sac was
      achieved in 27 patients. Acute conversion to open surgical repair was necessary
      in one patient, owing to arterial damage. Two patients had primary endoleak. In
      one patient the endoleak disappeared spontaneously, in the second patient
      conversion to open repair was performed during follow up. The operative mortality
      was 0%, and the incidence of early complications requiring treatment was 13%.
      During a median follow-up period of 22 months, secondary endoleaks were detected
      in five patients and graft-limb occlusion occurred in three patients. Secondary
      intervention was performed in eight patients (29%). DISCUSSION: In selected
      patients, endovascular repair is feasible and associated with few major
      perioperative complications. The observed rate of secondary intervention
      emphasises the need for continued surveillance.

PMID- 11989180
TI  - [Electronic medical records concerning patients of an ambulatory venereologic
      clinic. Background, structure and earlier experiences].

PMID- 11989181
TI  - [Opioid treatment of pain in angina pectoris].
AB  - We report four cases in which painful angina pectoris was treated with opioids on
      an as required basis. When the opioid treatment covering the 24-hour period had
      been established, the number of angina pectoris attacks was reduced by 75-90%.
      The remaining attacks became less intense. Long-term opioid therapy is
      complicated by physical dependency, as defined by withdrawal symptoms when the
      opioid is reduced or eliminated. Most patients do not recognise their withdrawal
      symptoms, and often the symptoms are mistaken simply as pain. Breakthrough
      withdrawal symptoms may occur as a consequence of opioid treatment administered
      on an as required basis.

PMID- 11989182
TI  - [Synchronous onset of collagenous colitis and Crohn disease].
AB  - A case report of a 69-year-old man with synchronous onset and diagnosis of
      collagenous colitis and Crohn's disease is discussed.

PMID- 11989183
TI  - [Picture of the month: Meckel's diverticulum].

PMID- 11989184
TI  - [Children, fat and cardiovascular disease].

PMID- 11989185
TI  - [Estimated consequences of the Danish sulfonamide treatment of uncomplicated
      urinary tract infections].

PMID- 11989186
TI  - A case of Wegener's granulomatosis without granulomas and with a negative C-ANCA.

PMID- 11989187
TI  - Tumor lysis syndrome secondary to Gemtuzumab Ozogamicin in a patient with acute
      myelogenous leukemia.

PMID- 11989188
TI  - Brodifacoum toxicity.

PMID- 11989189
TI  - Lewy body dementia.

PMID- 11989190
TI  - Cholesterol emboli syndrome occurring after administration of tissue plasminogen
      activator.

PMID- 11989191
TI  - Methicillin resistant Staphylococcus Aureus (MRSA) endocarditis secondary to
      tongue piercing.

PMID- 11989192
TI  - Eastern equine encephalitis presenting as psychosis.

PMID- 11989193
TI  - Henoch-Schonlein Purpura as a cause of renal failure in an elderly African
      American female.

PMID- 11989194
TI  - Nocardia farcinica osteomyelitis of the frontal bone five years after Nocardia
      brain abscess in an immunocompetent patient.

PMID- 11989195
TI  - Exophthalmos: a rare complication of systemic corticosteroids.

PMID- 11989196
TI  - Massive mediastinal and hilar adenopathy in a young African-American man.

PMID- 11989197
TI  - Upper extremity deep venous thromboses at Keesler Medical Center: 1997-2000.

PMID- 11989198
TI  - Intravenous immune globulin (IVIG) precipitating acute myocardial infarction.

PMID- 11989199
TI  - Granular cell tumors of the esophagus and colon.

PMID- 11989200
TI  - Levaquin induced acute tubulointerstitial nephritis--two case reports.

PMID- 11989201
TI  - Politically incorrect observations on how to help the Medicaid budget crisis.

PMID- 11989202
TI  - 9/11 remembered.

PMID- 11989203
TI  - Looking back: congenital syphilis in 1905.

PMID- 11989204
TI  - Provision of care to the underserved populations by National Health Service Corps
      alumni dentists.
AB  - OBJECTIVE: This study examined factors associated with dentists continuing to
      provide care to the underserved populations beyond their National Health Service
      Corps (NHSC) obligation period. METHODS: Self-administered questionnaires were
      mailed in 1998 to 404 dentists who had completed their service obligation between
      1980 and 1997. The outcome variable was dentist self-report of continuing to work
      with the underserved population past NHSC obligation. RESULTS: Among 249
      respondents (62% response rate), 46 percent of alumni dentists continued to work
      with an underserved population. Multivariate analyses found that being an African
      American (odds ratio [OR] = 3.2), higher final salary during the NHSC assignment
      (OR = 1.2), and higher altruistic motivation to work with the underserved
      populations prior to entering NHSC (OR = 1.1) were significantly associated with
      continued service to the underserved populations. CONCLUSIONS: A small number of
      factors were associated with alumni NHSC dentists' decisions to continue to
      provide care for the underserved populations. Targeting African-American students
      and students interested in caring for the underserved may improve the long-term
      commitment of dentists to provide care for the underserved populations. Attention
      will also need to be given to increased salary as a potential intervention to
      increase the numbers of dentists who continue to serve the underserved
      populations.

PMID- 11989205
TI  - Dental caries in the primary dentition: assessing prevalence of cavitated and
      noncavitated lesions.
AB  - BACKGROUND: Dental caries in the primary dentition has received renewed attention
      in recent years because caries in the primary dentition is predictive of later
      caries experience, and because of efforts to address early childhood caries. More
      detailed caries diagnostic criteria have been developed and used for the
      permanent teeth; however, such criteria have not been widely adopted for caries
      diagnosis in the primary dentition. METHODS: As part of the Iowa Fluoride Study,
      caries diagnostic criteria were developed specifically for the primary teeth. The
      criteria included noncavitated (d1) lesions and cavitated (d2-3) lesions.
      Examinations were conducted on 698 children in the primary dentition by two
      trained examiners who did duplicate examinations on 11 percent (n = 67) of these
      children. RESULTS: Interexaminer agreement for any d1 and any d2-3 lesions at the
      person level was 100 percent. At the tooth level for d1d2-3f, there was 98.5
      percent agreement and kappa was .91. For d1 at the tooth level, agreement was
      97.0 percent agreement and kappa = .24. For d2-3 it was 99.4 percent agreement
      and kappa = .81. Prevalence of untreated d2-3 was 16.5 percent, while that of d1
      was 24.1 percent. Nearly 73 percent had no d2-3 or filled surfaces, while over 63
      percent had no d1, d2-3, or filled surfaces. Decay experience was most common on
      the primary second molars. About 56 percent of untreated d2-3 decay was located
      in the pits and fissures, while 58 percent of d1 decay was located on smooth
      surfaces. CONCLUSION: Despite some concern with reliability of diagnosing d1
      lesions, it appears that the d1d2-3 criteria are informative and useful in
      assessing the primary dentition.

PMID- 11989206
TI  - Validation of self-reported periodontal measures among health professionals.
AB  - OBJECTIVE: The objective of this study was to determine the validity of self
      reported periodontal measures among nondentist health professionals. Valid self
      reported measures could provide a time- and cost-efficient alternative for large
      epidemiologic studies. METHODS: A subsample of 212 male nondentists sampled on
      the basis of their reported periodontal severity from the Health Professional
      Follow-up Study (HPFS) provided dental radiographs and completed questionnaires
      assessing self-reported oral health. Alveolar bone loss was evaluated from the
      radiographs at 32 posterior sites and used as the standard measure of cumulative
      periodontal disease. RESULTS: The self-reported ordinal periodontal measure had a
      linear relationship with mean radiographic bone loss (r = .61). The positive and
      negative predictive values of the dichotomized self-reported periodontal measures
      were 83 percent and 69 percent. Self-reported history of periodontal surgery was
      also a good surrogate for bone loss (predictive value positive 78 percent and
      negative 71 percent). CONCLUSIONS: Self-reports can provide discrimination and
      ranking information of cumulative periodontal disease among health professionals
      and can be used to provide valid results in etiologic studies in health
      professionals' populations.

PMID- 11989207
TI  - Validation of self-reported oral health measures.
AB  - OBJECTIVES: To assess the validity of self-reported oral disease and health care
      measures in two populations. METHODS: Telephone interviews were conducted among a
      subsample of participants in the VA Dental Longitudinal Study (VADLS) asking them
      about periodontal disease status and treatment. Radiographic alveolar bone loss
      evaluated at all the interproximal sites was used as the standard. A separate
      study was carried out among first-time patients at the Harvard School of Dental
      Medicine (HSDM) student clinic. Self-reported measures were obtained by a self
      administered questionnaire and compared with clinical and radiograph
      examinations. The measures used were based on published work that demonstrated
      good validity of self-reported periodontal measures among health professionals.
      RESULTS: Among 145 VADLS participants, self-reports of periodontal disease showed
      a good specificity (59.8%-90.7%), but low sensitivity (17.7%-64.7%). Among 58
      HSDM patients, the self-reported numbers of remaining teeth, fillings, root canal
      therapy, and prosthesis were strongly correlated with clinical records (r = 0.74
      1.0); self-report was less accurate for measures of periodontal disease (r =
      0.56) and decayed teeth (r = 0.47). CONCLUSIONS: Self-reports provide reasonably
      valid estimates for numbers of remaining teeth, fillings, root canal therapy, and
      fixed and removable prostheses. However, they appear to be less useful for the
      assessment of dental caries and periodontal disease in the two populations we
      have studied. There remains a need and potential to further develop self-report
      oral health measures that are valid for use in large population studies. Such
      self-report measures would yield great cost and time savings.

PMID- 11989208
TI  - The fight over water fluoridation in Israel--potential modes of action in light
      of the "American experience".

PMID- 11989209
TI  - General health status and changes in chewing ability in older Canadians over
      seven years.
AB  - OBJECTIVES: The purpose of this study was to describe the onset of and recovery
      from chewing problems in an older adult population over a seven-year period and
      to describe factors associated with these changes. Of particular interest was the
      relationship between general health and changes in oral functioning. METHODS: The
      data came from a longitudinal study of community-dwelling individuals who were
      aged 50 years and older when first recruited. Data were collected at baseline (n
      = 907) and at three (n = 611) and seven-year (n = 425) follow-ups. Oral function
      was assessed by means of a six-item index of chewing ability. Data were weighted
      to account for loss to follow-up using weights derived from the seven-year
      response proportions for dentate and edentulous subjects. Logistic regression
      analysis using backward stepwise selection was used to identify predictors of
      onset and recovery. RESULTS: At baseline, 25 percent of subjects reported a
      problem chewing. This rose to 26 percent at three years and 34 percent at seven
      years. The seven-year incidence of chewing dysfunction was 19 percent. Of those
      with a chewing problem at baseline, 21 percent did not have a problem at seven
      years. A logistic regression model predicting the seven-year incidence of chewing
      problems indicated that subjects aged 65 years or older, the edentulous, those
      rating their oral health as poor, those without dental insurance and those
      without a regular source of dental care were more likely to be an incident case.
      In addition, a variable denoting the number of chronic medical conditions at
      baseline also entered the model. A logistic regression model predicting recovery
      indicated that older subjects, the edentulous, those from low-income households,
      and those with limitations in activities of daily living were less likely to
      recover over the observation period. CONCLUSION: The results of this study
      indicate a marked increase in the prevalence of chewing problems in this older
      adult population over the seven-year observation period. Poorer general health at
      baseline increased the probability of the onset of a chewing problem and
      decreased the probability of recovery.

PMID- 11989210
TI  - Translation and validation of the Chinese version of GOHAI.
AB  - OBJECTIVE: To translate and validate the Chinese version of General Oral Health
      Assessment Index (GOHAI) for elderly in Hong Kong and to investigate factors that
      possibly may influence the GOHAI scores. METHODS: The English version of GOHAI
      was translated into Chinese. Persons aged 60-80 years were interviewed by two
      trained interviewers and clinically examined by a dentist. Information on
      subjects' demographic background and oral health conditions was collected.
      RESULTS: Altogether 1,023 elderly were interviewed and clinically examined. The
      mean GOHAI score was 48.9 (SD = 7.2). Cronbach's alpha of the translated GOHAI
      was 0.81; item-scale correlation ranged from 0.28-0.61. It was found that the
      mean GOHAI scores were lower for subjects with poorer perceived oral health (rs =
      0.57, P < .001). Elderly who had perceived dental treatment need had a lower mean
      GOHAI score than those who did not (P < .001). It was also found that elderly who
      lived in elderly homes, those who received social welfare assistance, those who
      had recent dental visits, and those with higher DMFT scores had higher mean GOHAI
      scores. CONCLUSION: The translated Chinese version of GOHAI demonstrated
      acceptable reliability and validity. It is available for use by researchers in
      oral health-related quality of life studies on Chinese elderly population.

PMID- 11989211
TI  - Oral health and use of dental services among Hispanics.
AB  - OBJECTIVES: This study examined factors related to oral health and dental service
      use among Mexican-Americans, Cuban-Americans, and Puerto Ricans from the Hispanic
      Health and Nutrition Examination Survey, 1982-84 (HHANES). METHODS: Categorical
      measures of oral health were created: (1) perceived oral health status, (2)
      evaluated oral health status, (3) decayed permanent teeth, (4) teeth missing due
      to caries, (5) total permanent teeth present, and (6) periodontal classification.
      The effects of acculturation, education, dental insurance, and perceived
      condition of teeth and gums on dental service use in the past two and five years
      were examined using logistic regression. All analyses were performed separately
      for each of the three samples using SAS-callable SUDDAN. RESULTS: Dental
      insurance and education were the most important factors in determining use of
      dental cleanings and use of dental care. For Mexican-Americans, Cuban-Americans,
      and Puerto Ricans, acculturation was a factor in determining use of dental care
      in the past five years. CONCLUSIONS: While dental insurance and education appear
      to be the most important factors for determining both use of dental cleaning
      services and use of dental care in all three samples, acculturation also had some
      impact for determining use of dental care.

PMID- 11989212
TI  - Periodontitis in the United States: beyond black and white.
AB  - OBJECTIVES: This paper examines whether historical disparities in periodontal
      status between African Americans and whites in the United States have increased,
      decreased, or remained the same over the 15-year period between the First
      National Health and Nutrition Examination Survey (NHANES I, 1971-74) and the
      Third National Health and Nutrition Examination Survey (NHANES III, 1988-94).
      METHODS: This study compared the magnitude of the relative and absolute
      differences in the periodontal status of African-American and white adults in
      NHANES I and again in NHANES III. RESULTS: The prevalence of periodontitis in the
      US adult population in NHANES I was 31.6 percent, with African Americans
      exhibiting higher prevalence than whites. In NHANES III, using a different case
      definition for periodontitis, the overall prevalence was 11.9 percent, with
      African Americans again exhibiting higher prevalence than whites. The magnitude
      of the intrasurvey relative and absolute differences between African Americans
      and whites increased between NHANES I and NHANES III. This finding remained after
      adjustment in the logistic regression analyses. After adjustment for all
      covariates in the model, African Americans were more likely to exhibit
      periodontitis than whites in both NHANES I (odds ratio [OR] = 1.31; 95%
      confidence intervals [CI] = .78, 2.19) and NHANES III (OR = 2.09; 95% CI = 1.68,
      2.60). However, the CI included 1.00 in NHANES I. CONCLUSIONS: Disparities in
      periodontitis between African Americans and whites are pervasive and have
      increased over time. This increase appears to be driven by social, cultural, and
      behavioral factors.

PMID- 11989213
TI  - How to pass on your expertise: a four-point approach to training physical
      examination skills in the outpatient setting.

PMID- 11989214
TI  - Insulin pump therapy.

PMID- 11989215
TI  - Rosiglitazone monotherapy and type 2 diabetes.

PMID- 11989216
TI  - Inhaled human insulin.

PMID- 11989217
TI  - Great suffering, great compassion: a transcultural opportunity for school nurses
      caring for Cambodian refugee children.
AB  - The cultural ways of Cambodian refugee families, combined with the physical and
      psychological health problems inherent in their refugee experience, present
      opportunities for nurses to engage in transcultural nursing. The purpose of this
      descriptive study was to understand the nature and meaning of a school district
      cross-cultural team's experiences of providing health care for children of
      Cambodian refugee families. Focus group interviews with school nurses and
      Cambodian liaisons were conducted utilizing S. M. Dobson's conceptual framework
      of transcultural health visiting as a guiding theoretical perspective.
      Transcultural and intracultural reciprocity as experienced with Cambodian
      families are explored and described. Concrete suggestions for fostering
      transcultural reciprocity with Cambodian refugee families are provided.

PMID- 11989218
TI  - Protegiendo Nuestra Comunidad: empowerment participatory education for HIV
      prevention.
AB  - To be effective, HIV/AIDS interventions must be culturally and linguistically
      appropriate and must occur within the context of the specific community in which
      they are delivered. In this article, the development of a culture-specific lay
      health advisor (LHA) program, Protegiendo Nuestra Comunidad, for recently
      immigrated Mexicans is described. This program is one component of a
      collaborative inquiry research project involving community participants and
      researchers working as partners in carrying out and assessing a program for the
      prevention of HIV/AIDS. The collaborative inquiry process was applied as an
      empowerment philosophy and methodology of Paulo Freire and an ecological
      framework was used for the development of Protegiendo Nuestra Comunidad. The use
      of principles of empowerment for curriculum development, teaching methodology,
      and program delivery are described.

PMID- 11989219
TI  - Factors associated with mammography utilization among Jordanian women.
AB  - This descriptive study aims at assessing beliefs and identifying factors that
      contributed to the utilization of mammography among a group of Jordanian women.
      Champion's Revised Health Belief Model Scales (HBMS) is the conceptual framework
      of this study. It was translated and adopted as the self-administered
      questionnaire utilized for the purpose of this study. The convenience sample was
      drawn from the women who had a mammography at a private radiology screening and
      diagnostic clinic in Amman over a 3-month period. Bivariate and multivariate
      analyses of the study variables were conducted. The results unveiled women's
      older age, hearing or reading about mammography, and receiving information about
      breast tumors from friends as factors predicting current mammography practice.
      Variables predictive of past mammography practice were related to the women's
      family or personal history of breast tumors and information about breast tumors
      from the media, in addition to information about mammograms from family members.

PMID- 11989220
TI  - Korean American family experiences of caregiving for their mentally ill adult
      children: an interpretive inquiry.
AB  - The purpose of this cross-cultural qualitative study is to describe and interpret
      the Korean American families' (KAFs') caregiving experiences for their mentally
      ill grown children. Seven KAF caregivers were purposefully sampled. In-depth
      audiotaped interviews were conducted in Korean, and Korean metaphors, images, and
      dreams were translated into English. This allowed for a rich explication of this
      study's complex caregiving phenomena. Five major themes were identified: (a)
      realization of children's illness, (b) battling the disease of incompetence, (c)
      poignant processes of caregiving, (d) suffering as a way of life, and (e) journey
      toward spirituality. In conclusion, incorporating transcultural nursing into core
      nursing curricula, recognizing the spiritual dimensions of care in nursing, and
      establishing culturally congruent community-based day treatment modalities and
      programs integrating other cultures are recommended.

PMID- 11989221
TI  - Being trapped in a circle: life after a suicide attempt in Taiwan.
AB  - The purpose of this hermeneutic phenomenological study was to understand how
      suicidal patients experienced their lives after attempted suicide. Ten
      participants were recruited from a medical center in Taiwan and were interviewed
      over a 5-month period about their experiences and feelings after their suicide
      attempts. Participants suffered from "being trapped in a circle" through three
      main avenues: (a) being controlled by others versus striving to live for oneself,
      (b) being rebuffed by others versus seeking company and being loved, and (c)
      wanting to leave family versus feeling responsible for family. These three themes
      were conceptualized under a broader theme of alienation versus connectedness.
      Cultural values, mientze (saving face), and hsiao (filial piety) influenced where
      those Chinese who had attempted suicide were located in the dimension between
      alienation and connectedness.

PMID- 11989222
TI  - Health-culture reorientation of registered nurse students.
AB  - There is a need for a health-culture reorientation of nurses from acute care to
      community-based care if the profession is to respond effectively to
      sociocultural, political, economic, and educational forces moving health care and
      decision making back into the community. Concepts from anthropology,
      international health, and transcultural nursing provided the basis for initiating
      a health-culture reorientation of acute care-oriented (RN-BSN) students enrolled
      in a population-based community health nursing course given in a weekend format.
      The course centered on developing a primary health care project from assessment
      data gathered via the community-as-partner model. Problems encountered, methods
      of evaluation, and ongoing project development are discussed.

PMID- 11989223
TI  - The bridging approach: effective strategies for teaching ethnically diverse
      nursing students.
AB  - This article describes one of the five patterns of teaching, the bridging
      pattern, which was identified by the author in a previous qualitative study that
      investigated the processes by which nurse educators teach ethnically diverse
      nursing students. An overview of the original study is presented, followed by a
      discussion of the findings regarding the bridging pattern. Data were obtained
      through in-depth interviews with 26 nurse educators and 17 nurses representing
      three population groups: Asian Americans, African Americans, and Mexican
      Americans. In the bridging pattern, educators encourage students to maintain
      their ethnic identity, and teaching-learning strategies are modified to meet the
      cultural needs of students. The conditions, actions and consequences involved in
      the bridging approach to teaching are described and examples that emerged from
      the data are presented as illustrations. Examination of the actions of the
      bridging faculty may assist educators to analyze their own approach to teaching
      ethnically diverse students.

PMID- 11989224
TI  - Health care ethics: cultural relativity of autonomy.

PMID- 11989225
TI  - Founder's focus: types of sciences and transcultural nursing knowledge.

PMID- 11989226
TI  - Prejudice, paradox, and possibility: nursing people from cultures other than
      one's own.
AB  - Nurses in New Zealand are being challenged to recognise and address racism in
      their practice. Yet, the implementation of cultural safety in nursing education
      has created tension within the profession and between nursing and the wider
      community. This article provides a brief overview of the findings of a
      hermeneutic study that explored the experience of nursing people from cultures
      other than one's own. The notions prejudice, paradox, and possibility are argued
      to describe this phenomenon. As nurses negotiate the conflicts essential for
      ongoing development of their practice, the play of prejudice, paradox, and
      possibility is evident at intrapersonal and interpersonal levels as well as in
      relation to professional and other discourses. Nurses are challenged to continue
      their efforts to understand and move beyond the prejudices that otherwise
      preclude the exploration of new possibilities.

PMID- 11989227
TI  - Adult male involvement in reproductive health: an ethnographic study in a
      community of Sao Paulo City, Brazil.
AB  - The purpose of this research was to explore the involvement in reproductive
      health of adult men in a low-income community in Sao Paulo City, Brazil. The
      ethnonursing research method was used and data were collected through interviews
      with seven key and eight general informants. Lack of common sex education was
      found and informants' knowledge depended on their own families' involvement and
      individual life experience with machismo. Informants' behaviors and attitudes
      toward women were constructed by their own male-centered values. Leininger's
      culture care modes were used to explain culturally meaningful nursing care
      actions and decisions.

PMID- 11989228
TI  - A survey of Hwa-Byung in middle-age Korean women.
AB  - Hwa-Byung (HB) has been categorized as a Korean culture-bound syndrome that
      refers to insidious, long-standing, serious discontent that is projected into the
      body and is manifested by numerous symptoms such as insomnia, fatigue, panic,
      palpitations, dyspnea, and others. This study was designed to investigate the
      prevalence rate of HB in Korean women, validate the predominant symptoms of HB,
      and validate the related sociodemographic factors and lifestyle factors that
      differentiate women with HB from those without HB. A total of 2,807 women ages 41
      to 65 years were recruited from seven metropolitan areas and six provinces in
      Korea. The prevalence rate of women who designated themselves as having
      experienced HB was 4.95%. The rates were higher in women of low socioeconomic
      status, living in rural areas, among the divorced or separated, smokers, and
      drinkers. A set of 31 HB symptoms differentiated the potential HB women from the
      non-HB women.

PMID- 11989229
TI  - The meaning of hope and generic caring practices to nurture hope in a rural
      village in the Dominican Republic.
AB  - The purpose of this study was to explore the meaning of hope and generic caring
      practices to nurture hope among people of a rural village in the Dominican
      Republic. Ethnonursing methods were used to gather and analyze data from which a
      definition of hope for this group of people was developed: "Hope is an essential
      but dynamic life force that grows out of faith in God, is supported by
      relationships, resources and work, and results in the energy necessary to work
      for a desired future. Hope gives meaning and happiness." The information obtained
      also demonstrated that hope interacts with nearly all domains in the Sunrise
      Model. Generic care practices discovered among this population included working
      together, advising each other to work hard, and sharing hope itself. Implications
      for further research are discussed.

PMID- 11989230
TI  - Challenges and strategies for conducting intervention research with culturally
      diverse populations.
AB  - Conducting intervention research with culturally diverse, underserved, and often
      hard to reach populations in naturalistic or field settings presents
      investigators with a number of practical challenges. This article describes four
      special challenges and strategies for dealing with them that clients, service
      providers, and researchers experienced in conducting a prevention intervention to
      reduce substance use and sexual risky behaviors with low-income Latina young
      women. The challenges are (a) building community partnerships; (b) developing
      interventions that are acceptable and relevant; (c) promoting successful
      recruitment, participation, and retention of participants; and (d) developing a
      diverse, cohesive, and committed research team and effective managerial
      information support systems.

PMID- 11989231
TI  - Weaving a transcultural thread.
AB  - This article describes the development and implementation of an educational
      strategy to enhance knowledge about transcultural nursing in a College of Nursing
      undergraduate program. Concepts of diversity and transcultural nursing were
      integrated into the entire undergraduate curriculum. This content was presented
      over six quarters in seminar courses throughout the undergraduate program. A team
      of faculty members developed this series of courses called "Nurse and Society"
      that included cultural diversity, ethics, professionalism, and policy as strands
      or threads woven through the courses. Based on faculty evaluations at the end of
      each course, most graduating students were aware of the need to provide
      culturally congruent care. However, there is a need to develop a sound
      programmatic evaluation that includes empirical outcomes of cultural competence
      among graduates.

PMID- 11989232
TI  - End of life customs among immigrants from Eritrea.
AB  - Eritrean immigrants bring expectations and resources to meet the challenge of
      illness and death. This study, undertaken in cooperation with the Cross Cultural
      Health Care Program of Seattle, sought to learn about both the expectations and
      the resources. A literature search demonstrated that although Eritreans have much
      in common with Ethiopians, they must be seen as a separate people. Open-ended
      interviews were conducted with 2 Eritrean immigrants. Resulting tape
      transcriptions were studied to identify themes and values. Values included the
      importance of respect, the centrality of faith and of family, the use of herbs
      and home remedies, and the importance of visiting. Implications for health care
      within institutional and community settings were derived from these values with
      the help of Madeleine Leininger's culture care theory.

PMID- 11989233
TI  - Transcultural nursing: can we meet the challenge of caring for the Australian
      Indigenous person?

PMID- 11989234
TI  - [Departmental review of surgical cases in the last 17 years: Colonic neoplasms].

PMID- 11989235
TI  - [Departmental review of surgical cases in the last 17 years: Liver neoplasms].

PMID- 11989236
TI  - [Departmental review of surgical cases in the last 17 years: Portal
      hypertension].

PMID- 11989237
TI  - [Departmental review of surgical cases in the last 17 years: Liver
      transplantation].

PMID- 11989238
TI  - [Departmental review of surgical cases in the last 17 years: Breast neoplasms].

PMID- 11989239
TI  - [Departmental review of surgical cases in the last 17 years: Lung neoplasm].

PMID- 11989240
TI  - [Departmental review of surgical cases in the last 17 years: Vascular diseases].

PMID- 11989241
TI  - [Departmental review of surgical cases during the past 17 years: Esophageal
      cancers].

PMID- 11989242
TI  - [Departmental review of surgical cases in the last 17 years: The Cancer Research
      Center].

PMID- 11989243
TI  - [Departmental review of surgical cases in the last 17 years: Da Vinci system].

PMID- 11989244
TI  - [Departmental review of surgical cases in the last 17 years: Stomach cancers].

PMID- 11989245
TI  - [Physiopathology of chronic obstructive lung disease and progress in its
      therapy].

PMID- 11989246
TI  - [Emergency treatment for autoimmune diseases].

PMID- 11989247
TI  - [Systemic complications in patients with rheumatism and collagen disease and
      their treatment].

PMID- 11989248
TI  - [Progress in therapy for chronic heart failure].

PMID- 11989249
TI  - [Clinical studies on atrial fibrillation].

PMID- 11989250
TI  - [Complications in hemodialysis].

PMID- 11989251
TI  - [Diagnosis and treatment of kidney failure].

PMID- 11989252
TI  - [Progress in diagnosis and treatment of lung cancer].

PMID- 11989253
TI  - [Diagnosis and treatment of COPD].

PMID- 11989254
TI  - [Therapy of hematologic disorders with stem cell transplantation].

PMID- 11989255
TI  - [Chemotherapy of hematological malignancies based on EBM].

PMID- 11989256
TI  - [Progress in diagnosis and treatment of lung cancer].

PMID- 11989257
TI  - [Present status and treatment of drug resistance in bacterial infections].

PMID- 11989258
TI  - [Diagnosis and treatment of pneumonia].

PMID- 11989259
TI  - [Diagnosis and treatment of pulmonary embolism].

PMID- 11989260
TI  - [Practice guidelines for diagnosis and treatment of Helicobacter pylori
      infections and their application in clinical practice].

PMID- 11989261
TI  - [Progress in diagnosis and treatment of Crohn disease].

PMID- 11989262
TI  - [Recent progress in liver transplantation].

PMID- 11989263
TI  - [Physiopathology of pancreatitis and its treatment].

PMID- 11989264
TI  - [Prevention of liver neoplasms].

PMID- 11989265
TI  - [Emergency treatment for hepatobiliary and pancreatic disease].

PMID- 11989266
TI  - [Emergency endoscopy for the upper gastrointestinal tract].

PMID- 11989267
TI  - [Prevention of recurrence in cerebral infarction].

PMID- 11989268
TI  - [Emergency treatment for cerebrovascular disease].

PMID- 11989269
TI  - [Emergency treatment for endocrine and metabolic diseases ].

PMID- 11989270
TI  - [Coronary artery disease in patients with diabetes mellitus and its treatment].

PMID- 11989271
TI  - Hospital competition is being elevated to clinical performance.

PMID- 11989272
TI  - Siemens introduces Sorian work-flow-focused information system.

PMID- 11989273
TI  - HCA is a Wall Street favorite again.

PMID- 11989274
TI  - Cap Gemini Ernst & Young creates new practice to focus on medical outcomes.

PMID- 11989275
TI  - When you survey physicians, know that blacks, Hispanics, whites, males and
      females disagree.

PMID- 11989276
TI  - InfoFair: an annual computer and information event.
AB  - Since 1983, the Spencer S. Eccles Health Sciences Library has presented InfoFair,
      an annual event featuring presentations, exhibits, demonstrations, and workshops
      on computer and information topics of interest to health professionals and health
      information providers at the University of Utah Health Sciences Center and
      throughout Utah. The first InfoFair was held in response to an increasing number
      of inquiries from library users on how to search MEDLINE from their home or
      office computers. The focus of InfoFair has expanded and changed over the past
      nineteen years to reflect changes in library users' computer and information
      needs, concerns, and interests. While themes and programs have changed, a
      definite set of trends, guidelines, and procedures have developed based on the
      experience gained each year. The purpose of this paper is to review and evaluate
      the changes in InfoFair from 1983 to 2001 and to present information for use by
      other libraries for planning and presenting similar events.

PMID- 11989277
TI  - Online use statistics.
AB  - Online use statistics can provide libraries with a tool to be used when
      developing an online collection of resources. Statistics can provide information
      on overall use of a collection, individual print and electronic journal use, and
      collection use by specific user populations. They can also be used to determine
      the number of user licenses to purchase. This paper focuses on the issue of use
      statistics made available for one collection of online resources.

PMID- 11989278
TI  - Consumer health services and collections for Hispanics: an introduction.
AB  - Hispanics are the fastest growing minority population in the United States today.
      Providing health information services to Hispanic patients and their family
      members can be challenging because of diversity. Library staff should be familiar
      with the specific health care needs and sociocultural characteristics of
      Hispanics. This article discusses the movement toward providing culturally
      competent health care and identifies socioeconomic challenges and barriers to
      health care faced by Hispanics. Suggestions are offered for communicating with
      this group in the reference setting, and a selective bibliography of Internet
      consumer health resources available in both Spanish and English is provided.

PMID- 11989279
TI  - ChemIDplus-super source for chemical and drug information.

PMID- 11989280
TI  - Community outreach through Web resources: multiple sclerosis.

PMID- 11989281
TI  - A hospital archives ... what's it all about?
AB  - Establishing a hospital archives can be a daunting, though exciting project, with
      many positive outcomes. The description of archives, in general, and the
      distinctions of a hospital archives, specifically, are presented. The initial
      steps which need to be considered when developing a hospital archives are
      detailed using the Maine Medical Center Archives as an example.

PMID- 11989282
TI  - Bridging the distance: bibliographic instruction for remote library users.
AB  - Electronic information resources are proliferating, library collections are
      increasingly accessible via the Internet, and the number of end users who access
      library resources remotely is on the rise. Changes in user behavior drives a
      corresponding change in the way instructional programs must be delivered to meet
      the needs of remote library users. This paper discusses some technologies
      currently available for remote instruction, assesses their use, and offers views
      on future trends.

PMID- 11989283
TI  - [Activity of nucleolar organizers in the cells of erythroblastic islands in the
      bone marrow in various erythropoietic functional states].
AB  - Erythroblastic islands (EIs) of the bone marrow are the morpho-functional units
      of the erythron. The functional state of the cells of EIs of varying maturity was
      first studied by estimating the activity of nucleolar organizers in intact rats
      and in rats with acute blood loss or posttransfusion polycythemia by the modified
      method of J. Croker and P. Nar. The intact rats had the largest number of
      nucleoli and intranuclear argentum inclusions located within and outside the
      nucleoli in EIs of proliferating classes: Class 1 EIs and reconstructing EIs and
      the smallest number in involutional EIs. Blood loss was accompanied by the
      enhanced activity of nucleolar organizers in EI cells. In polycythemia, the
      activity of the organizers changed in a more complicated manner.

PMID- 11989284
TI  - [The role of neutrophils in the regulation of antimicrobial resistance].
AB  - The functional activity of neutrophils and macrophages and an immune response to
      sheep red blood cells decrease in mice with local staphylococcal infection in the
      early period. In the first 24 hours after contamination, the animals' neutrophils
      lose their capacity to produce immuno-stimulating agents, they begin secreting
      immunosuppressive factors. Administration of secretory products of activated
      neutrophils, the low-weight molecular peptide isolated from these cells to the
      induced animals restores the immunological responsiveness of the staphylococcus
      infected animals, reduces the death of mice infected with S. aureus and S.
      typhimurium.

PMID- 11989285
TI  - [Examining the properties of hepatic cytosol and the efficiency of its use in the
      Biological Support Liver apparatus].
AB  - Clinical trials showed the minimum efficiency of various detoxifying methods
      (dialysis, charcoal adsorption, plasma exchange) in terms survival in acute
      hepatic insufficiency. Attempts were made to provide hepatic functions through ex
      vivo perfusion of the whole liver and tissue sections, but these methods remain a
      challenge to immune responses and blood clotting. This led to the development of
      the extracorporeal liver support systems and early clinical results encouraged
      further work in this area. The liver support system consists of a bioreactor
      containing a liver homogenate, a transfer mechanism, and a dialyzer that connects
      2 closed contours. The apparatus is connected to the patient's blood system by
      means of an arteriovenous or venovenous shunt. The contact time of a liver
      homogenate and a patient's blood in the dialyzer and the diffusion rate of
      molecules of chemical substances determine the detoxifying and metabolic effects.
      Laboratory studies have demonstrated that the detoxifying activation method has
      high effects (increased biotransformation, decreased blood ammonia levels),
      decreases the intensity of pathological processes, normalizes blood components
      (higher levels of ATP, glucose, amino acids, vitamin C). Model and experimental
      studies of the efficiency of the method lead to the conclusion that it is
      expedient to apply it in medical practice.

PMID- 11989286
TI  - [Diode lasers in ophthalmic surgery].
AB  - The paper outlines current aspects of the use of diode lasers in ophthalmology.
      The Ufa Research Institute of Eye Diseases is the first in Russia to develop and
      use endoscopic cyclic laser coagulation and laser endoscopic antegrade
      dacryocystorhinostomy. The introduction of new laser microendoscopic technologies
      into practical ophthalmology has increased the efficiency of ophthalmological
      care in the treatment of patients with non-compensated glaucoma and lacrimal duct
      diseases.

PMID- 11989287
TI  - [Clinical and neurophysiological characteristics of motor cortical responsiveness
      during prolonged cranial osteoplasty].
AB  - The data of global and stimulation poly-EMG were used to estimate the outcomes of
      multimodality treatment of sequelae of brain injury and stroke, which was based
      on the vasoactive effects of prolonged cranial osteoplasty. Thirteen patients (7
      males and 6 females) aged 19 to 64 (mean 42 +/- 4) years who had signs of left-
      (n = 2) and right-sided (n = 11) spastic hemiparesis. Global and stimulation poly
      EMG, which involved recording and analysis of resting and total EMG under the
      maximum voluntary tension, M-waves H-reflexes, transcranially evoked potentials.
      The muscles of the shoulder, forearm, hand, femur, leg, and foot were studied.
      The surgical procedure developed at the Russian Research Center "VTO" for
      stimulation of cerebral blood flow in combination with conventional conservative
      treatments (physiotherapy, therapeutical exercises, and adequate drug therapy)
      was shown to increase the transmission coefficient of an efferent signal in the
      motor cortex-spinal motor neurons-muscle system, which is clinically accompanied
      by improved coordination of simple and complex movements realized with the
      participation of the muscles of both the paretic and contralateral extremity. The
      ambiguous effects of the vasoactive factors of prolonged osteoplasty on the
      functions of unequally modal pathologically changed cerebral motor structures
      were noted. The findings may be considered as evidence for the low traumatic
      ability of the VTO's techniques for replacing posttraumatic defects of skull
      vault bones.

PMID- 11989288
TI  - [New methods for the studying of erythropoiesis in humans and animals].
AB  - New approaches to studying erythropoiesis in man and animals on the basis of a
      quantitative and qualitative analysis of this process in the erythroblastic
      islands of the bone marrow are shown. Experimental and clinical data are given,
      which reflect the results of testing these approaches. Ideas on physiological and
      compensatory erythropoiesis in the erythroblastic islands of the bone marrow and
      on the manifestations of its suppression in these intercellular associations are
      presented.

PMID- 11989289
TI  - [Homeostasis and paravasal damper structures in intact and damaged nerves and
      long tubular bones].
AB  - Sciatic and tibial nerves and a femoral osteotomic area were investigated in
      experiments on 36 adult mongrel dogs during neutral and distractional
      osteosynthesis. Histological and X-ray studies, computer-assisted image analysis,
      and statistical methods were used. The morphological basis of hemodynamic
      features of the nerves and long tubular bones was characterized. The mechanisms
      responsible for perivascular osteogenesis in the bone marrow cavity and for
      hypertrophy of perineural cell paravasal spongy structures in the nerves were
      studied as compensatory and adaptive responses to changes in the hemodynamical
      components of homeostasis after bone injury and during extremity stretching.

PMID- 11989290
TI  - [The functional status of the cerebral cortex after replacement of skull base
      bone defects].
AB  - The functional status of the cerebral cortex was evaluated by EEG before and
      different periods after prolonged cranial osteoplasty made by the type of
      replacement of skull base bone defects in patients with dyscirculatory
      encephalopathies of various genesis. Seven patients aged 20 to 50 years undergone
      repair of skull base bone defects (both posttraumatic and simulated) by the
      procedures developed at the Russian Research Center "VTO" were examined. The
      bioelectrical activity of the brain was recorded and analyzed on a PEGASUS
      digital 16-channel EEG system (EMS, Austria) by using the Fourie prompt
      conversion test (spectral analysis) and amplitude-frequency mapping. After
      multimodality treatment, all the patients showed a positive changes in the whole
      range of EEG parameters, which appeared as an increase in basic rhythm power, a
      decrease in the focal area of slow-wave activity and in the interhemispheral
      asymmetry coefficient, which in combination of neurological regression is
      regarded as indirect evidence for the vasoactivity of prolonged cranial
      osteoplasty.

PMID- 11989291
TI  - [Impact of transrectal microwave hyperthermia on hemodynamics and prostatic cell
      membranes in chronic prostatitis].
AB  - An Aden-Ch apparatus programming complex made in our country was used for
      transrectal microwave hyperthermia in 75 patients with chronic prostatitis. In
      addition to its good clinical results achieved in most patients, the complex
      restored hemodynamics and stabilized the status of prostatic cell membranes. The
      complex described in the paper may be recommended for the treatment of chronic
      prostatitis.

PMID- 11989292
TI  - [Fundamental and applied aspects of neuroendocrine regulation of pro- and
      eukaryote interactions].
AB  - The paper presents the results of light, atomic-force, and electron microscopic
      studies of prokaryotes (various Staphylococcus aureus strains) and eukaryotes
      (Rat digestive and respiratory cells and tissues) in in vivo and in vivo
      interactions. It is concluded that hypothalamic nonapeptides play a modulating
      role in the persistence and symbiotic relations in the bacterium-host system and
      regulate cellular and tissue homeostasis through reparative histogenesis.

PMID- 11989293
TI  - [The first experience with photo-neutron therapy: advantages, problems].

PMID- 11989294
TI  - [Epidemiology of osteoporosis].

PMID- 11989295
TI  - [Regularities of hemopoietic development in bone marrow erythroblastic islands
      during early ontogenesis].
AB  - Erythroblastic islands (EIs) of the bone marrow are multicellular associations of
      erythroid and macrophage cells. EIs serve as morpho-functional units of
      erythropoiesis. Erythropoiesis was studied in the rat liver, spleen, and bone
      marrow on days 1, 3, 7, 10, 15, and 30 after birth. Changes in the number of EIs
      and in their composition were simultaneously examined. After birth,
      erythropoiesis was shown to decrease in the liver and spleen, but it became more
      active in the bone marrow. There were islands of nondifferentiated hemopoietic
      cells on day 1 after birth, mixed hemopoietic islands on day 3, and a drastic
      increase in bone marrow EIs on day 7. On day 30, the levels of EIs were the same
      as in adult rats. There was a close relationship between the number of EIs and
      that of erythroid cells in the bone marrow, as well as the count of red blood
      cells. The age-specific dynamics of quantitative and qualitative changes in EIs
      and erythropoiesis is presented.

PMID- 11989296
TI  - [Sentinel lymph node diagnosis in prostatic carcinoma: II. Biokinetics and
      dosimetry of 99mTc-Nanocolloid after intraprostatic injection].
AB  - AIM: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the
      radiotracer into the parenchyma of the prostate. The activity was deposited in
      liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The
      aim of this work is to determine biokinetical data and to estimate radiation
      doses to the patient. METHODS: The patients with prostate cancer received a
      sonographically controlled, transrectal administration of 99mTc-Nanocoll,
      injected directly into both prostate lobes. In 10 randomly selected patients
      radionuclide distribution and its time course was determined via regions of
      interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph
      nodes. The uptake in the SLNs was estimated from gamma probe measurements at the
      surgically removed nodes. To compare tumour positive with tumour free lymph nodes
      according to SLN-uptake and SLN-localisation we evaluated 108 lymph nodes out of
      24 patients with tumour positive SLN. For calculating the effective dose
      according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1
      software. RESULTS: The average uptake of separate organs was: bladder content
      24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied
      activity remained in the prostate. The residual activity was mainly accumulated
      in bone marrow and blood. Occasionally a weak activity enrichment in intestinal
      tract and kidneys could be recognized. The effective dose to the patient was
      estimated to 7.6 microSv/MBq. The radioactivity uptake of the SLN varied in
      several orders of magnitude between 0.006% and 0.6%. The probability of SLN
      metastasis was found to be independent from tracer uptake in the lymph node. The
      radioactivity uptake of the SLNs in distinct lymph node regions showed no
      significant differences. CONCLUSION: The radiotracer is transferred out of the
      prostate via blood flow, by direct transfer via the urethra into the bladder and
      by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean
      effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in
      lymph nodes as the only criterion to characterize SLNs.

PMID- 11989297
TI  - Lymph node staging in extracranial head and neck cancer with FDG PET--appropriate
      uptake period and size-dependence of the results.
AB  - AIM: Identification of a rationale for the appropriate uptake period for static
      clinical extracranial head and neck PET imaging and evaluation of the diagnostic
      accuracy of such an optimized FDG PET approach for lymph node staging in the head
      and neck region. METHODS: In a subset of 5 patients, kinetic tumour studies were
      performed in order to identify the cellular activity plateau phase of FDG
      accumulation for head and neck cancer. Seventy-eight consecutive patients (11
      women, 67 men; mean age +/- SD: 55 +/- 11 years; range, 36-78 years), presenting
      with histologically proven squamous cell carcinoma and sonographically detected
      lymph nodes in 86 neck sides, underwent clinically indicated FDG PET imaging. PET
      results were compared to those derived from histological examinations and follow
      up imaging results after 6 months in order to calculate sensitivity and
      specificity for lymph node staging. RESULTS: FDG kinetics in head and neck cancer
      indicate that the cellular activity plateau of FDG accumulation is reached after
      an uptake period of 90 min. Using this protocol metastatic involvement of neck
      sides with lymph nodes less than 1 cm in diameter was correctly identified with a
      sensitivity of 71.4% and a specificity of 92.3%. Sensitivity increased with the
      lymph node diameter (1.1-1.5 cm 83.3%, 1.6-2.0 cm 100%, > 2 cm 88.9%).
      CONCLUSION: The appropriate uptake period for static clinical extracranial head
      and neck PET imaging that allows measurements in the activity plateau phase is
      about 90 min. FDG PET may add some significant information regarding metastatic
      spread into regional lymph nodes.

PMID- 11989298
TI  - [Multivariate analysis of factors influencing the effect of radiosynovectomy].
AB  - OBJECTIVE: In this prospective study, the time to remission after
      Radiosynovectomy (RSV) was analyzed and the influence of age, sex, underlying
      disease, type of joint, and duration of illness on the success rate of RSV was
      determined. METHODS: A total number of 57 patients with rheumatoid arthritis (n =
      33) and arthrosis (n = 21) with a total number of 130 treated joints (36 knee, 66
      small and 28 medium-size joints) were monitored using visual analogue scales
      (VAS) from one week before RSV up to four to six months after RSV. The patients
      had to answer 3 times daily for pain intensity of the treated joint. The time
      until remission was determined according to the Kaplan-Meier survivorship
      function. The influence of the prognosis parameters on outcome of RSV was
      determined by multivariate discriminant analysis. RESULTS: After six months, the
      probability of pain relief of more than 20% amounted to 78% and was significantly
      dependent on the age of the patient (p = 0.02) and the duration of illness (p =
      0.05), however not on sex (p = 0.17), underlying disease (p = 0.23), and type of
      joint (p = 0.69). CONCLUSION: Irrespective of sex, type of joint and underlying
      disease, a measurable pain relief can be achieved with RSV in 78% of the patients
      with synovitis, whereby effectiveness is decreasing with increasing age and
      progress of illness.

PMID- 11989299
TI  - [How many high-risk patients with differentiated thyroid cancer need a "Tumor
      Center" per year?].

PMID- 11989300
TI  - [Graves' disease nd toxic nodular goiter--radioiodine therapy].
AB  - At the 15th conference on the human thyroid in Heidelberg in 2001 the following
      aspects of the radioiodine therapy of benign thyroid disorders were presented:
      General strategies for therapy of benign thyroid diseases, criterions for
      conservative or definitive treatment of hyperthyroidism as first line therapy and
      finally preparation, procedural details, results, side effects, costs and follow
      up care of radioiodine therapy as well as legal guidelines for hospitalization in
      Germany. The diagnosis Graves' hyperthyroidism needs the decision, if rather a
      conservative treatment or if primary radioiodine therapy is the best therapeutic
      approach. In the USA 70-90% of these patients are treated with radioiodine as
      first line therapy, whereas in Germany the conservative therapy for 1-1.5 years
      is recommended for 90%. This review describes subgroups of patients with Graves'
      disease showing a higher probability to relapse after conservative treatment.
      Comparing benefits, adverse effects, costs, and conveniences of both treatment
      strategies the authors conclude that radioiodine therapy should be preferred as
      first line therapy in 60-70% of the patients with Graves' hyperthyroidism.

PMID- 11989301
TI  - Radioiodination of monoclonal antibodies, proteins and peptides for diagnosis and
      therapy. A review of standardized, reliable and safe procedures for clinical
      grade levels kBq to GBq in the Gottingen/Marburg experience.
AB  - Simple and reliable methodologies for radioiodination of proteins and peptides
      are described. The labeling systems are easy to assemble, capable of
      radioiodinating any protein or, with slight modifications, also peptide
      (molecular mass 1000-300,000) from kBq to GBq levels of activity for use in
      diagnosis and/or therapy. Furthermore, the procedures are feasible in any nuclear
      medicine department. Gigabecquerel amounts of activity can be handled safely. The
      most favored iodination methodology relies on the lodogen system, a mild
      oxidating agent without reducing agents. Thus, protein degradation is minimized.
      Labeling yields are between 60 and 90%, and immunoreactivities remain > or = 85%.
      Other radioiodination methods (chloramine-T, Bolton-Hunter) are described and
      briefly discussed.

PMID- 11989302
TI  - [Assessment of endocrine disorders of the hypothalamic-pituitary axis by nuclear
      medicine techniques].
AB  - The following article reviews nuclear medicine techniques which can be used for
      assessment of endocrine disorders of the hypothalamic-pituitary axis. For planar
      and SPECT imaging somatostatin-receptor- and dopamine-D2-receptor-scintigraphy
      are the most widely distributed techniques. These nuclear medicine techniques may
      be indicated in selected cases to answer differential diagnostic problems. They
      can be helpful to search for presence and localization of receptor positive
      tissue. Furthermore they can detect metastasis in the rare cases of a pituitary
      carcinoma. Scintigraphy with Gallium-67 is suitable for further diagnostic
      evaluation in suspected hypophysitis. Other SPECT radiopharmaca do not have
      relevant clinical significance. F-18-FDG as PET radiopharmacon is not ideal
      because obvious pituitary adenomas could not be visualized. Other PET
      radiopharmaca including C-11-methionine, C-11-tyrosine, F-18
      fluoroethylspiperone, C-11-methylspiperone, and C-11-raclopride are available in
      specialized centers only. Overall indications for nuclear medicine in studies for
      the assessment of endocrine disorders of the hypothalamic-pituitary-axis are
      rare. Original studies often report only about a small number of patients.
      According to the authors' opinion the relevance of nuclear medicine in studies of
      clinically important endocrinologic fields, e.g. localization of small ACTH
      producing pituitary adenomas, tumor localization in ectopic ACTH syndrome,
      localization of recurrent pituitary tissue, assessment of small incidentalomas,
      can not be definitely given yet.

PMID- 11989303
TI  - Introduction of helical computed tomography affects patient selection for V/Q
      lung scan.
AB  - AIM: Retrospective analysis for determination of the effect of helical computed
      tomography (HCT) on utilization of V/Q lung scanning to diagnose pulmonary
      embolism (PE) in a large general hospital. METHODS: A total number of 2676 V/Q
      scans of in- and out-patients referred to our department between March 1992 and
      December 1998 and between April 1997 and December 1998 were analyzed by an
      identical group of nuclear physicians. RESULTS: Neither the total number of
      annually performed V/Q scans (446 +/- 135) nor the mean age of patients (56 years
      +/- 17) changed significantly since the introduction of HCT. However, the
      referral pattern was different. The percentage of patients with high and
      intermediate probability for PE decreased significantly from 15.2% to 9.4% (p <
      0.01) and from 10.2% to 7.3% (p < 0.05), respectively. Low probability scans
      significantly increased from 37.8% to 42.7% (p < 0.05). The percentage of normal
      scans did not change significantly, however, there was a highly significant
      increase summarizing patients with normal and low probability scans (74.6% to
      83.3%; p < 0.01). CONCLUSION: The introduction of HCT affected the selection of
      patients referred for V/Q lung scanning since V/Q scanning was primarily used to
      exclude rather to confirm PE.

PMID- 11989304
TI  - [Sentinel lymph node diagnosis in prostatic carcinoma: I: Method and clinical
      evaluation].
AB  - AIM: Evaluation of the significance of lymphoscintigraphy and intraoperative
      probe measurement for the identification of the sentinel lymph node (SLN) in
      prostate cancer. PATIENTS AND METHOD: In 117 patients with prostate cancer
      scintigrams in various projections were acquired till approximately 6 hours p.i.
      after ultrasound guided transrectal intraprostatic injection of 99mTc-Nanocoll.
      On the following day the SLNs were identified in the operation theatre with a
      gamma probe and removed. Pelvic standard lymph node dissection followed SLNE.
      RESULTS: In three of 117 patients with preoperative lymphoscintigraphy no SLN was
      scintigraphically detectable. These three patients had antecedent transurethral
      resection of the prostate. In 113 of the residual 114 patients SLN could be
      intraoperatively localized. In the mean four SLNs per patient were removed. 28 of
      117 patients had pelvic lymph node metastases. In 25 cases SLN were right
      positive, in one false-negative and in one intraoperatively not detectable. In
      one patient we found macrometastasis of up to 4 cm diameter (one SLN was tumour
      positive). In 15 cases only the SLN was bearing tumour. CONCLUSION: The SLNE with
      preoperative lymphoscintigraphy and intraoperative gamma probe measurement is
      suitable for detecting lymph node metastasis in prostate cancer. SLNE is superior
      to the surgical techniques commonly used in pelvic lymphadenectomy.

PMID- 11989305
TI  - Increased F-18 fluorodeoxyglucose accumulation in a benign neurofibroma--a
      pitfall in a patient with thyroid cancer: a case report.

PMID- 11989306
TI  - Assessing health in our rural communities.

PMID- 11989307
TI  - Knowledge and use of folic acid among North Carolina women.

PMID- 11989308
TI  - Buncombe County Medical Society Project Access. Expanding access to care at the
      local level.

PMID- 11989309
TI  - Access to care for North Carolina's uninsured.

PMID- 11989310
TI  - Why is fair access so hard to achieve? The North Carolina Medical Society
      explores solutions.

PMID- 11989311
TI  - Hospitals and the uninsured. Straining the safety net.

PMID- 11989312
TI  - The uninsured and Medicaid.

PMID- 11989313
TI  - Small business responds to the crisis in healthcare.

PMID- 11989314
TI  - Affordability. Key issue for the uninsured.

PMID- 11989315
TI  - Progress toward Healthy People 2000. Physical activity and weight status in
      eastern North Carolina.

PMID- 11989316
TI  - The view from the east.

PMID- 11989317
TI  - Healthcare in eastern North Carolina.

PMID- 11989318
TI  - Pedophilia.

PMID- 11989319
TI  - The thin line between love and lust.

PMID- 11989320
TI  - The pros and cons of Botox.

PMID- 11989321
TI  - Rome: can we talk?

PMID- 11989322
TI  - Breaking the cycle. Can the children of convicts learn not to be like their
      parents?

PMID- 11989323
TI  - Getting better. A health retreat offers a jump start on the road to wellville.

PMID- 11989324
TI  - More blame and praise for a pain drug.

PMID- 11989325
TI  - Alzheimer's treatment. Heart and brain.

PMID- 11989326
TI  - Oral concerns in Lyme disease.

PMID- 11989327
TI  - High definition: a practice philosophy at work.

PMID- 11989328
TI  - Headed in the right direction.

PMID- 11989329
TI  - Small town practices--a great way of life.

PMID- 11989330
TI  - In service of others.

PMID- 11989331
TI  - Will there be a shortage of dental auxiliaries in the future?
AB  - The number of graduates from dental hygiene programs continues to increase, but
      retention of dental hygienists in practices is a concern. The numbers of
      graduates from dental assisting and especially dental laboratory technology
      programs are decreasing. The impact on dental practice size and practice
      productivity is considered.

PMID- 11989332
TI  - Platelet rich plasma. The use of autologous growth factors to enhance bone and
      soft tissue grafts.
AB  - The addition to a graft site of an easily obtained autologous concentrate of
      blood platelets, called platelet rich plasma (PRP), offers improved quality and
      faster healing for both hard and soft tissue. This article will outline the
      sequence of bone regeneration, the role of PRP in bone regeneration, the methods
      to acquire PRP and the uses for PRP in clinical practice.

PMID- 11989333
TI  - Geriatric dentistry. A review for the general dentist.
AB  - In the 20th century, the oral health of Americans, along with their life
      expectancy, improved dramatically. The 21st century offers dental professionals
      the opportunity to help patients maintain their oral health for a lifetime.

PMID- 11989334
TI  - Strange bedfellows.

PMID- 11989335
TI  - Endodontic patency. How to get it. How to keep it. Why it is so important.
AB  - Complete elimination of the root canal contents is imperative for predictable
      endodontic success. Establishing and maintaining apical patency of the root canal
      system is critical for proper cleaning, shaping and obturating objectives,
      despite timidity about this region in the past. Contemporary concepts are
      discussed.

PMID- 11989336
TI  - Chief executives. Off limits.
AB  - Trust remuneration committees are paying chief executives above the limits
      recommended in Department of Health guidance. In doing so they are ignoring the
      government's stated policy of fair pay for all in the NHS and their duty of
      accountability. Excessive awards made by a remuneration committee can be subject
      to judicial review and overturned. The health secretary should review the
      workings of trust remuneration committees and ensure that their decisions are
      transparent to the public.

PMID- 11989337
TI  - Open space. True lies.

PMID- 11989338
TI  - Hospitals accelerate spending on lobbying. With results such as the restoration
      of billions in balanced-budget law relief, nobody's complaining.

PMID- 11989339
TI  - Providers keep up soft money.

PMID- 11989340
TI  - Is it worth the wait? Visa delays threaten U.S. market share, hospitals say.

PMID- 11989341
TI  - UNOS records requested. Liver transplant programs of Chicago hospitals under
      probe.

PMID- 11989342
TI  - Big brewings in a small town. Tenet could face competition in Missouri.

PMID- 11989343
TI  - Jewish-Norton dispute boils over. An unusual proposal to cut out a rival goes
      embarrassingly public.

PMID- 11989344
TI  - Healthcare in need of a fix. Unless there is systemic change, the system is like
      the Titanic, headed for an iceberg.

PMID- 11989345
TI  - Double standards. Amid push for nurse ratio laws, the nation's hospitals also
      face new JCAHO requirements for measuring staffing effectiveness.

PMID- 11989346
TI  - Web survey. March results: 'nurse staffing--beyond the ratios'.

PMID- 11989347
TI  - More dollars for New York.
AB  - With the shock from Sept. 11 still fresh, the Greater New York Hospital
      Association, led by Kenneth Raske, left, went ahead and did what had to be done,
      crunching numbers to attempt to quantify the staggering loss. Last week its hard
      work paid off when HHS announced another round of emergency funding to healthcare
      organizations that suffered direct losses from the terrorist attacks.

PMID- 11989348
TI  - [ICU resources can be utilized in a better way. Choose the right patient and the
      right moment for the intensive care, make priorities when it comes to the ethical
      issues and introduce the in-between "step-down ICU"].

PMID- 11989349
TI  - [Is dopamine in acute renal failure a treatment of the past?].

PMID- 11989350
TI  - [When is the intensive care patient ready for discharge?].
AB  - Prognostic factors for ICU-patients during and after ICU-discharge are reviewed
      as well as predisposing factors for readmissions. The overall mortality for ICU
      patients are in most studies in the range of 12-32%, with a mortality rate after
      ICU discharge of 15-35%. Prognostic factors for mortality include age, severity
      of illness, diagnosis, multi-organ failure, nosocomial infections and a prolonged
      ICU stay. Readmissions to ICU are not uncommon and usually (45-65%) related to
      the underlying illness. The use of High Dependency Units or a sufficient ICU
      capacity might reduce the mortality rate as well as the rate of readmissions.

PMID- 11989351
TI  - [Dopamine and loop-diuretics are not beneficial in acute kidney failure. New
      therapeutic strategies are required].

PMID- 11989352
TI  - [The facial expression says more than words. Is emotional "contagion" via facial
      expression the first step toward empathy?].
AB  - The hypotheses of this investigation were based on the conception of automatic
      mimicking being an early component involved in the formation of emotional
      empathy. The parameters compared were facial mimicry reactions, as represented by
      electromyographic (EMG) activity when subjects were exposed to pictures of angry
      or happy faces, and the degree of correspondence between facial EMG reactions and
      their own reported feelings. The subjects in the high-empathy group were found to
      have a higher degree of mimicking behaviour, while the low-empathy group showed
      inverse zygomaticus muscle reactions; they "smiled" when exposed to angry faces.

PMID- 11989353
TI  - [Cataract in children after autologous bone marrow transplantation. A common, but
      curable complication].
AB  - Bone marrow transplantation (BMT) is an established treatment of hematological
      malignancies in children. With a rapidly increasing number of long-term
      survivors, more attention is focused on late sequelae to this therapy. Several
      cataractogenic factors are involved in BMT, such as ionizing irradiation,
      corticosteroid treatment, and chemotherapeutic agents. Lens opacity is therefore
      a potential late side-effect of BMT. The incidence and degree of cataract in 29
      children who had undergone autologous or syngeneic BMT were recorded. Median
      follow-up was eight years (4-10 years). 21 children had received total body
      irradiation prior to BMT; they all developed cataract of the posterior
      subcapsular type after three years (median). Six children needed surgical repair
      in the form of intraocular lens implantation after extracapsular cataract
      extraction.

PMID- 11989354
TI  - [Multifocal motor neuropathy--unusual cause of hypoglossal palsy].
AB  - Multifocal motor neuropathy with conduction block (MMN-CB) very rarely presents
      with cranial nerve symptoms. We describe a 72-year old man who was referred for a
      neurological evaluation because of a one-year long history of right-sided
      hypoglossal palsy with fasciculations. Since the examination also revealed slight
      atrophy in the hands, a motor neuron disease (MND) was suspected. The
      neurophysiological examination revealed bilateral ulnar conduction blocks
      indicative of MMN-CB. The patient was treated with lvlg and improved
      considerably. A short review of MMN-CB and of hypoglossal palsies is presented.
      This is, to the best of our knowledge, the first case described in which MMN-CB
      presents with hypoglossal palsy.

PMID- 11989355
TI  - [Management of radiation injuries--new organization, new guidelines].
AB  - The medical management of radiation accident victims is based on a rapid
      assessment and reconstruction of the radiation dose and quality combined with
      prompt, targeted treatment efforts performed at specialized medical units. To
      facilitate such medical emergency preparedness in Sweden, the National Board of
      Health and Welfare has recently established a new Centre for Radiation Medicine,
      located at the Karolinska institute in Stockholm. Among the tasks of this centre
      are also to contribute with health care information, education, advice and carry
      out research activities in areas related to medical effects of ionizing
      radiation. A close collaboration is being established with the Swedish Radiation
      Protection Authority and also with various other national and international
      bodies. The initiation of the Centre for Radiation Medicine comes in parallel
      with a rapid development of the understanding of and treatment options for
      patients acquiring an acute radiation syndrome, mainly due to improved diagnostic
      procedures combined with novel therapeutic options, such as stem cell
      transplantation and cytokine administration.

PMID- 11989356
TI  - [Antithrombin therapy of no value in sepsis according to a large clinical trial].
AB  - Antithrombin has been used for over two decades as adjuvant therapy in severe
      sepsis, especially when associated with coagulopathy. A positive effect has been
      demonstrated in several experimental sepsis models and a number of small clinical
      trials have suggested a beneficial effect. A large confirmatory randomized
      clinical trial with 2,314 evaluable patients with severe sepsis was recently
      completed [1]. No treatment effect of antithrombin was demonstrated (28 day
      overall mortality was 38.9% and 38.7% in the treatment and placebo groups,
      respectively). Among various secondary effect and subgroup analyses, it is
      noteworthy that no trend indicating a beneficial effect of antithrombin
      substitution was found even in the subgroup of patients with plasma levels of
      antithrombin < 60% on randomization (n = 1,117). In summary, there is presently
      no support for the general use of antithrombin as adjuvant therapy in severe
      sepsis/septic shock.

PMID- 11989357
TI  - [Prolonged postoperative thromboprophylaxis--current state of knowledge].
AB  - By "prolonged thromboprophylaxis" is usually meant around 30 days
      postoperatively. This modality using low molecular heparin in patients undergoing
      total hip replacement has been shown to be effective as regards incidence of both
      phlebographically detected deep vein thrombosis and--in meta-analysis--clinical
      venous thromboembolism. It is important to identify further risk groups who may
      be in need of prolonged thromboprophylaxis. Recent data suggest that patients
      undergoing abdominal/pelvic surgery for malignant diseases belong to such a
      group.

PMID- 11989358
TI  - [Increased risk of death because of cardiovascular disease among women who had
      had pre-eclampsia].

PMID- 11989359
TI  - [You can inform her, right... Breaking the news about cancer requires well
      considered structure and empathy].

PMID- 11989360
TI  - [Palm computer--a mini notebook for physicians].

PMID- 11989361
TI  - [Regular palm computer with many useful functions for health personnel].

PMID- 11989362
TI  - [Big and heavy but the keyboard is good].

PMID- 11989363
TI  - [A software for physicians with mobile offices].

PMID- 11989364
TI  - [Medical IT progress in American health care].

PMID- 11989365
TI  - [Cost savings proposals concerning health services require good knowledge].

PMID- 11989366
TI  - [After 400 years anatomy lost its position as an institution of its own. A
      retrospect of the rising and fall of the Uppsala anatomicum].

PMID- 11989367
TI  - ["Organisation's delay"--a concept connected to the distribution of
      responsibility in health care].

PMID- 11989368
TI  - [The "murder of honour"--is it really the correct term?].

PMID- 11989369
TI  - [Internship examination--low-price quality assurance which should remain].

PMID- 11989370
TI  - [The compulsory psychotherapy training should include all specialties. Deficient
      education is expensive for the society].

PMID- 11989371
TI  - [Somatization--an expression for an obsolete view on disease].

PMID- 11989372
TI  - [Private practices in Stockholm are not in danger, but not everybody wants to
      consult a down-town specialist].

PMID- 11989373
TI  - [Surrogate research on heart disease and risk factors].

PMID- 11989374
TI  - Endoscope- and video-assisted endodontic surgery.
AB  - Since the introduction of microsurgical principles in the 1990s, the field of
      endodontic surgery has made continuous and substantial progress. Particularly,
      root-end cavity preparation has been simplified and optimized by means of newly
      developed surgical microinstruments. However, the successful outcome of
      endodontic surgery depends to a large extent on accurate intraoperative
      diagnostics. Conventionally, micromirrors (retromirrors) and microprobes have
      been used for this purpose. Recently, the surgical microscope has been used to
      enhance visibility during dental procedures. In addition, endoscopy has been
      reported to provide the surgeon with outstanding vision and ease of use. This
      article describes the technical specifications and the diagnostic application of
      the endoscope during endodontic surgery.

PMID- 11989375
TI  - An in vivo evaluation of hemorrhage control using sodium hypochlorite and direct
      capping with a one- or two-component adhesive system in exposed nonhuman primate
      pulps.
AB  - OBJECTIVE: This study evaluated the biologic ability of sodium hypochlorite to
      control hemorrhage via chemical amputation of the coagulum, to remove dentin
      chips, to assist healing, and to facilitate formation of a dentinal bridge under
      two adhesive systems. METHOD AND MATERIALS: Ninety Class V cavities with
      mechanical pulpal exposures were placed in the teeth of five adult monkeys and
      histologically observed. All exposures were prepared with a No. 330 bur, and
      hemorrhage was controlled with 3% sodium hypochlorite. Twenty-two exposures were
      capped with All-Bond 2 and AElitefil, and 26 exposures were capped with One-Step
      (OS) and Resinomer (RS). Two pulps were excluded from the final data. Forty-two
      exposures were capped with calcium hydroxide and amalgam as controls. At 7, 27,
      and 90 days, tissues were obtained by perfusion fixation, demineralized,
      sectioned, stained, and histologically graded according to published qualitative
      criteria. RESULTS: For both adhesives, at 7 days, 12 of 16 pulps showed no
      coagulum remnants or dentin chips at the material interface. No necrotic pulps
      were observed. At 27 and 97 days, 26 of 30 capped pulps had dentinal bridges at
      the adhesive interface. Reparative dentin was present in 28 pulps. Four 97-day
      pulps exhibited necrosis associated with stained bacteria. One 97-day pulp
      contained dentin chips throughout the pulp and demonstrated no healing, no
      reparative dentin, and no stained bacterial profiles. CONCLUSION: Normal soft
      tissue reorganization and dentinal bridge formation were observed in 86% of pulps
      treated with sodium hypochlorite and either adhesive system.

PMID- 11989376
TI  - Replacement of resin-based composite: evaluation of cavity design, cavity depth,
      and shade matching.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of different cavity
      designs, cavity depths, and shade matching on the dimensions of Class I resin
      based composite preparations during replacement of the restoration. METHOD AND
      MATERIALS: Forty Class I cavity preparations were prepared in extracted
      premolars. The occlusal depths varied from 1.5 to 2.5 mm. In 20 teeth, the buccal
      and lingual walls were perpendicular to the pulpal floor; in another 20, they
      were divergent to the pulpal floor. Impressions were made of all preparations.
      The cavities were restored with resin-based composite. All subgroups were further
      divided into another two subgroups (n = 5), in which half of the teeth were
      restored with shade that matched the tooth and the other half were restored with
      a resin composite that was three shades different from the tooth. After 168 hours
      in distilled water, the restorations were removed. New impressions were made, and
      a total of 80 stone casts were fabricated. The perimeter and area of the
      restorations were recorded with a video-based imaging system. The dimensions of
      the postoperative cavity preparations were compared to the initial cavity sizes.
      RESULTS: The depth of the original cavity preparation had a statistically
      significant effect on the change in cavity dimension, as measured by area and
      perimeter. The 2.5-mm-deep cavities showed greater loss of tooth structure. No
      statistically significant difference was found for different cavity designs or
      shade matching. CONCLUSION: Replacement of Class I resin-based composite
      restorations results in loss of tooth structure. The deeper the original cavity
      preparation, the greater the loss of tooth structure at the occlusal cavosurface
      margin during replacement.

PMID- 11989377
TI  - Evaluation of cutting patterns produced in primary teeth by an air-abrasion
      system.
AB  - OBJECTIVE: The aim of this in vitro study was to assess the effect of tip
      diameter, nozzle distance, and application time of an air-abrasion system for
      cavity preparation on the enamel of primary teeth. METHOD AND MATERIALS: Forty
      exfoliated primary teeth were air abraded with a microabrasion machine used with
      a handpiece with an 80-degree-angle nozzle, 50-micron abrasive particle size, and
      80-psi air pressure. The effects of 0.38- or 0.48-mm inner tip diameter, 2- or 5
      mm distance from tip to tooth surface, and 15 or 30 seconds of application time
      on cutting efficiency were evaluated. Cutting width and depth were analyzed and
      measured from scanning electron micrographs. RESULTS: Statistical analysis
      revealed that the width of the cuts was significantly greater when the tip
      distance was increased. Significantly deeper cavities were produced by a tip with
      a 0.48-mm inner diameter. The application time did not influence the cuts.
      CONCLUSION: The cutting patterns found in this study suggest that precise removal
      of enamel in primary teeth is best accomplished when a tip with a 0.38-mm inner
      diameter is used at a 2-mm distance.

PMID- 11989378
TI  - The importance of the seated condylar position in orthodontic correction.
AB  - It has been proposed that the discrepancy between the seated and unseated
      condylar position be identified and eliminated when the occlusion is reorganized.
      Identification of this discrepancy is most accurately accomplished through the
      use of diagnostic casts that have been taken from a deprogrammed patient and
      mounted in the seated condylar position on a semiadjustable articulator through
      an estimated facebow transfer. The amount and direction of any discrepancy is
      determined three dimensionally with condylar position instrumentation.

PMID- 11989379
TI  - Hypodontia: etiology, clinical features, and management.
AB  - Patients who are congenitally missing one tooth or more are frequently
      encountered in routine practice. The etiology, classification, and clinical
      features of hypodontia are reviewed, and treatment modalities are discussed. One
      case of mild-to-moderate hypodontia and one case of severe hypodontia are
      described. Osseointegrated implants have provided encouraging results, especially
      in patients who are missing anterior teeth or who have severe hypodontia.

PMID- 11989380
TI  - Primary anterior tooth replacement with a fixed prosthesis using a precision
      connection system: a case report.

PMID- 11989381
TI  - Serving the poorest of the poor: the story of Jeremiah J. Lowney.
AB  - Since 1966, Dr Jerry Lowney has practiced orthodontics in Norwich, Connecticut,
      where he has been active in both community and professional organizations,
      including the University of Connecticut Board of Trustees and the Board of
      Governors for Higher Education. Since his first volunteer trip to Haiti in the
      mid-1980s, during which he provided dental services for the poor, he has returned
      to that country at least three times each year. Over time the nature of his
      activities has changed. Through grant writing, personal influence, liaison with a
      religious order, a huge investment of time, successful fundraising, the seizing
      of every opportunity, and the expenditure of large amounts of his own money, he
      has created a multimillion-dollar general health facility in one of the poorest
      areas in Haiti. Besides dental treatment, the scope of his activities has ranged
      from creating centers for high-risk pregnancy and malnutrition to the hiring of
      physicians, the training of local nurse practitioners, and an Adopt-a-Family
      program run by his wife, Virginia. His actions have been influenced by Virginia's
      caring attitudes and by his conviction that much is expected from those who have
      received life's bounties.

PMID- 11989382
TI  - Tardive dyskinesia.

PMID- 11989383
TI  - A meeting of the minds. John Paul II calls the U.S. cardinals to Rome. Let the
      damage control begin.

PMID- 11989384
TI  - The right way to read.

PMID- 11989385
TI  - Reconsidering HRT.

PMID- 11989386
TI  - An act of faith?

PMID- 11989387
TI  - The dental team--PCDs. Where are we now?
AB  - Professionals Complementary to Dentistry (PCDs) have varying roles within the
      dental team, from chairside assisting to the actual provision of clinical
      treatment. These tasks are closely proscribed at present, but this may change in
      the future. The modernization of dentistry, the introduction of registration for
      PCDs, the introduction of workforce development confederations responsible for
      funding and commissioning training of dentists and PCDs, and a workforce review
      looking at the whole dental team will all impact upon the working lives of
      dentists and their teams. These current changes represent an opportunity to
      improve the functioning and composition of the dental team, which should not be
      missed.

PMID- 11989388
TI  - The management of gingival recession.
AB  - This, the second paper in a short series on gingival recession, discusses the
      various modalities of treatment for gingival recession and the indications for
      treatment. Special consideration is given to the surgical treatment techniques.
      Factors affecting the outcome of treatment and success rates of the treatment
      options are also discussed.

PMID- 11989389
TI  - Preserving the vital pulp in operative dentistry: 2. Guidelines for successful
      restoration of unexposed dentinal lesions.
AB  - The exciting treatment possibilities arising from tissue engineering approaches
      are still some years away from involvement in dentistry. Meanwhile, it is
      important to optimize conventional treatments, although precise information on
      pulp responses to cavity preparation and restoration variables are limited.
      Odontoblast survival, pulp inflammation, and tertiary dentine area are used as
      measures of pulp injury and repair.

PMID- 11989390
TI  - Traumatic overbite: a restorative solution.
AB  - Deep overbite is frequently seen in the adult dentition. Although the condition
      is usually asymptomatic, certain factors may lead to the development of deep
      traumatic overbite, and in partially dentate patients loss of posterior occlusal
      support may be a contributory factor. Several treatment modalities, including
      orthodontics, orthognathic surgery and prosthodontics have been used but, as some
      adult patients with this problem are unwilling to avail themselves of treatment
      involving either orthodontics or orthognathic surgery, a restorative approach
      using a combination of fixed and removable restorations may provide a
      satisfactory solution. This paper details a case report on the restorative
      management of a partially dentate adult patient with a deep traumatic overbite.

PMID- 11989391
TI  - Orofacial paraesthesia: an unusual presentation of acoustic neuroma.
AB  - Patients with acoustic neuromas commonly present with unilateral hearing loss,
      tinnitus and unsteadiness. An uncommon initial feature is involvement of the
      trigeminal nerve. The unusual feature in the case reported here was orofacial
      paraesthesia, which preceded hearing loss by 3-4 years. Diagnosis was made
      following a referral by the patient's dentist.

PMID- 11989392
TI  - Hyaluronan and its potential role in periodontal healing.
AB  - Hyaluronan is a natural tissue component, which plays a vital role in the
      functioning of extracellular matrices, including those of the periodontium. This
      molecule is also important in relation to the mechanisms associated with
      inflammation and wound healing. The application of exogenous hyaluronan and
      hyaluronan-based biomaterials has been successful in manipulating and
      accelerating the wound healing process in a number of medical disciplines, as
      evident in ophthalmology, dermatology and rheumatology. It is conceivable that
      hyaluronan administration to periodontal sites could achieve comparable
      beneficial effects in periodontal healing and surgery, hence aiding treatment of
      periodontal disease.

PMID- 11989393
TI  - The progression of appoximal caries lesions--a clinical observation.

PMID- 11989394
TI  - Old but not forgotten.

PMID- 11989395
TI  - An April Fool's Day commentary. What a difference a scale makes!

PMID- 11989396
TI  - The arrival and departure of a baffling disease.

PMID- 11989397
TI  - The evolution of transplantation in Rhode Island.

PMID- 11989398
TI  - Blood and marrow stem cell transplantation at the Roger Williams Medical Center,
      1999-2001.

PMID- 11989399
TI  - Infections in the transplant recipient.

PMID- 11989400
TI  - Live donor renal transplantation.

PMID- 11989401
TI  - An update in transplant immunosuppressive therapy.

PMID- 11989402
TI  - Images in medicine. Pneumocystis carinii choroiditis.

PMID- 11989403
TI  - Diabetes and heart disease.

PMID- 11989404
TI  - Drug product expiration dates: practice implications.

PMID- 11989405
TI  - Diabetes: an epidemic of a chronic disease.

PMID- 11989406
TI  - Asthma, particulates, and diesel exhaust.

PMID- 11989407
TI  - Hands on medicine.

PMID- 11989408
TI  - An answer for Sandra.

PMID- 11989409
TI  - Health care delivery. The waiting list reality.
AB  - How can nurses effectively advocate for improvements in waitlist management? This
      is a challenge, as they witness the negative effects of poorly administered
      referrals.

PMID- 11989410
TI  - Family ties. Grandparents raising grandchildren.
AB  - When grandparents are raising their children's children, family dynamics change
      considerably. Nurses can be instrumental in assessing these clients in their
      health care needs, and providing education and support.

PMID- 11989411
TI  - Point-of-care documentation.
AB  - A custom-made software application can make electronic charting of patient goals
      and outcomes simple and quick for the nurse, as well as making it easier for
      decision-makers to identify problem areas.

PMID- 11989412
TI  - Cyberlaw.

PMID- 11989414
TI  - Research columns a hit.

PMID- 11989413
TI  - Time for a special issue on aboriginal health.

PMID- 11989415
TI  - Reconnecting the spirit of healing.
AB  - The history of health care was the history of the church until the advent of
      scientific medicine. Now, through parish nursing, "the church's role has been
      reclaimed," says Gail Brimbecom, a Canadian pioneer in this growing specialty.

PMID- 11989416
TI  - About retiring.

PMID- 11989417
TI  - Being there.

PMID- 11989418
TI  - Skyrocketing medical malpractice premiums threaten Georgia hospitals.

PMID- 11989419
TI  - A case for tort reform.

PMID- 11989420
TI  - Leadership styles.

PMID- 11989421
TI  - CMS criticizes quality oversight of ambulatory surgery centers.

PMID- 11989422
TI  - [Hemorrhagic cystitis caused by BK and JC polyomavirus in patients treated with
      bone marrow transplantation: clinical features and urologic management].
AB  - INTRODUCTION: Differential diagnosis of hematuria after bone marrow
      transplantation (B.M.T.) may include polyomavirus (BK and JC)-associated
      haemorrhagic cystitis. Many reports have implied BK virus as the major pathogen
      in the development of hemorrhagic cystitis after BMT. BK viruria is also
      associated with ureteric stenosis in renal allografts recipients. Viral urinary
      tract infections are uncommon in healthy individuals, but we can find them
      frequently in patients under immunosuppressive conditions. MATERIAL AND METHODS:
      Retrospective study of 123 consecutive B.M.T. recipients in the period from 1995
      to 2000, evaluating those with polyomavirus-associated hemorrhagic cystitis. We
      present patient's characteristics, primary disease, clinical features, diagnosis
      aspects and treatment of these "hidden hosts of urinary tract". RESULTS: 7
      patients (5.7% of B.M.T.) developed BK or JC virus-associated hemorrhagic
      cystitis; 3 men and 4 women; median patient age was 29 years (range 14 to 45
      years). Bacterial, mycobacterial and parasitic urine cultivates had negative
      results in all of them. The clinical course was characterized by a late onset of
      haemorrhagic cystitis (days +30 to +132 after BMT). All 7 patients developed
      macroscopic haematuria (duration 3 to 30 days). In 6 cases Graft Versus Host
      Disease (G.V.H.D.) criteria were found. Ultrasonographic studies revealed diffuse
      thickening of bladder wall in 5 patients. Hematuria was managed by
      hyperhydratation, blood transfusions, transurethral catheter and evacuation of
      blood clots, continuous bladder irrigation, urine alkalinization and antiviral
      therapy. No other more aggressive measures were required to stop the bleeding.
      Only 1 case of transient elevated creatinine. CONCLUSIONS: Polyomavirus
      associated haemorrhagic cystitis must be considered in differential diagnosis of
      hematuria in bone marrow transplantation recipients. Urological management,
      according with the severity and duration of hematuria, is frequently required.

PMID- 11989423
TI  - [Metabolic risk factors in calcium urolithiasis according to gender and age of
      the patients].
AB  - INTRODUCTION: Little information is available on the metabolic changes found in
      relation to gender and aging in patients with urolithiasis. In this study a
      comparison has been made of the metabolic profiles in men and women, in different
      groups of aging, with calcium-containing urinary stones in order to identify
      possibly significant differences. MATERIAL AND METHODS: In the past five years, a
      total of 500 patients with calcium-containing urinary stones, 226 male (45.2%)
      and 274 female (54.8%), have undergone comprehensive metabolic evaluation. The
      mean age was 47.4 years, with a range of 20 to 75 years. The patients was
      included in 3 groups: 151 patients aged 20-39 years, 255 patients aged 40-59
      years and 94 patients aged 60-75 years. A comparison has been made of the
      frequency of metabolic changes, the urinary biochemical parameters and the
      supersaturation index (AP(CaOx)) between a group of men and a group of women and
      the different groups of aging. All patients carried out in an identical manner to
      metabolic diagnosis. The patients with morphologic and functional abnormalities
      were excluded. RESULTS: Hyperoxaluria, hyperuricosuria and hypocitraturia were
      more common in men than in women, whilst in women, hypercalciuria and a low
      urinary volume were more frequent with respect to men, though the differences in
      hypercalciuria were not statistically significant. Men excrete higher levels of
      calcium, phosphate, oxalate, uric acid and magnesium than women. On the other
      hand, women excrete higher levels of citrate than men. The AP(CaOx) index is
      significantly higher in men than in women. Hypercalciuria were more common in
      patients aged < 60 years, and low urinary volume were more frequent in patients
      aged < 40 years. Patients aged < 60 years excrete higher levels of calcium,
      phosphate and uric acid. The AP(CaOx) index is significantly higher in patients
      aged < 60 years. CONCLUSIONS: Differences were observed between the metabolic
      profiles of men and women, and in different groups of aging. Men and younger
      patients afford a metabolic profile of upper lithogenic risk compared with women
      and older patients; this is consistent with the upper reported prevalence of
      lithiasis and the upper tendency to recurrence in men and middle-age patients.

PMID- 11989424
TI  - [Nd-YAG laser photocoagulation of scrotal sebaceous cysts].
AB  - Scrotum's sebaceous cyst is an usual pathology, not life threatening, but
      susceptible of infection, producing abscess with their associated cosmetic and
      psychological disturbance. The classical management is the complete excision,
      under local anaesthesia, to prevent its recidive. Until today, the use of de Nd
      YAG laser for the management of the scrotum's sebaceous cysts as not been
      reported. We report a case of a young man with several scrotum's sebaceous cysts,
      treated successfully with the use of a Nd-YAG laser.

PMID- 11989425
TI  - [Bilateral adrenal metastasis as first clinical manifestation of pulmonary
      carcinoma: report of a case and review of the literature].
AB  - Bilateral adrenal metastases are rare, and the first manifestation from non-small
      cell lung cancer is also exceptional. We report a case of bilateral adrenal
      metastases from a poorly differentiated lung adenocarcinoma in a 50 year-old-man.
      The treatment was local excision of tumor and the diagnosis was histological. We
      comment the clinical presentation, diagnosis, treatment and evolution of this
      case, with special attention to the histopathological analysis of this lesion and
      literature review.

PMID- 11989426
TI  - [Primary testicular lymphoma. Report of a case].
AB  - Case report of a primary testicular lymphoma in a sixty-two years old man,
      presenting initially as an enlargement of the testicle as the only symptom.
      Orchiectomy of left testicle was performed, with the diagnosis of Non-Hodgkin B
      lymphocytic lymphoma. The treatment applied was CHOP, presenting poor evolution
      with cerebral metastasis. He dead twenty-five months later diagnosis.

PMID- 11989427
TI  - [Subepithelial hematoma of kidney pelvis and ureter: Antopol-Goldman lesion].
AB  - The subepithelial hematoma of the renal pelvis and ureter was described by
      Antopol and Goldman in 1948. Hematuria and filling defect in the renal pelvis are
      the most consistently recurring clinical and radiological findings. Only 21 cases
      were found in the literature on the subject and all of them were treated
      surgically, usually with partial or total nephrectomy. Here we present a case of
      Antopol-Goldman lesion which was treated conservatively.

PMID- 11989428
TI  - [Vesico-urethral lithiasis secondary to foreign body].
AB  - We report a case of vesico-urethral litiasis secondary to foreign body (gauze)
      calcificated, left in prostatic cell during prostate open surgery of performed
      twelve years ago. In the related literature we observe that most of foreign
      urinals bodies are secondary to the introduction through the urethra of objects
      with autoerotic finality in normal patients or more often with psychiatric
      disorders, and only a small proportion are of iatrogenic origin, mainly in the
      last ten years.

PMID- 11989429
TI  - [Appendix mucinous cystadenoma].
AB  - Mucous cystadenomas are benign epithelial tumours with great mucous content
      inside. Despite being non-malignant, they acquired great size, compressing and
      displacing important structures and organs of the zone, with theirs unlucky
      outcomes. Surgical exeresis is very difficult, being almost impossible its total
      exeresis, showing great frequency of relapse. We present an appendix mucous
      cystadenoma case in a 54 years old patient.

PMID- 11989430
TI  - [Penile adenoma: clinical case].
AB  - Penile melanoma is a very uncommon neoplasm, being reported less than 60 cases.
      Event yet it outlines not few doubts about its diagnosis and treatment, and in
      advanced stages represents a challenge for the future since it prognosis is awful
      at short time. In the present article, its presented a glans melanoma diagnosed
      and treated at our Service. We make a brief revision of the literature and some
      basic issues on the management of this entity when it's localized in penis, since
      in the cases in which it extends far from this organ is yet oncological field.

PMID- 11989431
TI  - [Computer-controlled isolated kidney hypothermic perfusion system].
AB  - OBJECTIVE: To evaluate at the laboratory a self-designed computer-controlled
      kidney perfusion system. A vacuum powered tubular pump with active valves
      developed by our group is used. This pump is able to produce a flow and pressure
      patterns very similar to the pulse wave in the human circulatory system. BASIC
      PROCEDURES: This is an experimental study performed with mini-pig kidneys. After
      transperitoneal bilateral nephrectomy, both organs are sorted either to immediate
      perfusion or to perfusion after a period of 24 hours of cold storage in
      Eurocollins solution. The system is able to record continuously perfusion
      pressure, flow and intrarenal resistance. RESULTS: A progressive decrease in
      renal vascular resistance along with an increase in the flow value were observed
      during the procedures. These dynamic changes become evident both in immediate and
      deferred renal perfusions. CONCLUSIONS: Computer-controlled kidney perfusion
      system provide us the opportunity of recording in real time renal
      microcirculatory state modifications during a perfusion. Vascular system seems to
      be actively modified by the perfusion. This fact should be researched in the next
      future.

PMID- 11989432
TI  - [Endoscopic ureteral resection in radical nephroureterectomy: report of our
      experience].
AB  - We want to present our clinic and chirurgical experience in eight patients, using
      the radical nephroureterectomy with endoscopical resection of the ureter, as a
      safe and valid technique, in urothelial tumours localized in the upper urinary
      tract.

PMID- 11989433
TI  - [Intratesticular calcifications: clinical significance].
AB  - OBJECTIVE: [corrected] To evaluate the clinical-pathological significance of the
      intratesticular calcification. MATERIAL AND METHODS: We analyzed by scrotal U.S.,
      transducer 6.5 Mhz, the patients that consulted about testicular painful,
      infertility or intrascrotal deformity. Biopsy was effectuated when detected size
      modification of testicles, and central or focal calcifications. Also was done the
      classics tumoral markers. We founds 16 patients with microlithiasis over 24
      testicles with these pathology. Previous antecedents: infertility 6 cases,
      testicular devolvulations surgery 5c, bilateral orchidopexy 3c and unilateral
      epididymitis 2c. The calcifications was classified in: peripheric or central
      follow-up 26.4 months. RESULTS: Associated pathology: a) Bilateral
      cryptorchidism: 4 testicles. b) Testicular tumors: 5 testicles. These tumors were
      biopsed: 3 seminomas, 1 embryonary carcinoma and 1 ca in situ. Both with negative
      biologic markers. The association with testicular tumor had an incidence of
      20.83%. The central localization was detected in the 5 tumors, while the
      peripheric were 4 testis (cryptorchidism) and 15 with aspect of "snow storm".
      Histopathologically was observed eosinophilic bodies, with calcified nucleus, but
      not a exclusive features. CONCLUSIONS: Is a benign condition, casual, whose
      clinical significance is a still enigma. The association with testicular tumor is
      20.83% and associated pathology is 33%. We proposed a testicular biopsy in cases
      of microlithiasis focal, central or with previous pathology.

PMID- 11989434
TI  - [Prognostic value of P53, Ki67, and Rb protein in infiltrating bladder tumors].
AB  - OBJECTIVES: To determinate whether increased expression of the p53 and Ki67 and
      the of the tumour suppressor gene retinoblastoma (prot Rb), in an
      immunohistochemistry study, were associated with relapse in invasive bladder
      cancer. MATERIALS AND METHODS: 47 patients with invasive bladder cancer. 42 men
      and 5 women. Mean age 63 years old. Relapse in 19 patients (40%). Mean time until
      recurrence 8.5 months. p53 and Ki67 were study in 47 patients and prot Rb in 40
      patients. RESULTS: p53: Mean expression 41%. There were significant differences
      in the increased expression of p53 between patients with and without relapse (p =
      0.03). A statistically significant association was then observed between patients
      with p53 > 20% (vs p53 < 20%) and adverse outcome of the disease (p = 0.04). Ki67
      and prot Rb: There were no significant differences in relapse and progression
      free survival between Ki67 > 40% (vs Ki67 < 40%) and prot Rb < 10% (vs prot Rb >
      10%). p53 expression showed a statistically significant correlation with Ki67 and
      prot Rb. CONCLUSION: p53 is a good prognostic marker for the relapse and
      progression free survival in invasive bladder cancer.

PMID- 11989435
TI  - Supreme Court gives strict interpretation to Disabilities Act language. Toyota
      Motor Manufacturing v. Williams.

PMID- 11989436
TI  - Court rules no-hire provision unenforceable. Heyde Companies v. Dove Healthcare
      LLC.

PMID- 11989437
TI  - Evidentiary privilege for peer review documents rejected by the Fourth Circuit.
      Virmani v. Novant Health Inc.

PMID- 11989438
TI  - Wynand Pieter Dreyer.

PMID- 11989439
TI  - Liber testimonii: A Festschrift in honor of the late Philip L.Chambers (deceased
      August 30, 1999).

PMID- 11989440
TI  - [Dr. Tadataka Yamada].

PMID- 11989441
TI  - Correlation between work experiences and physical assessment in Japan.
AB  - The purpose of this study was to obtain baseline data of Japanese nurses'
      knowledge, skills and attitudes concerning physical assessment. The design of the
      study was survey research, using a self-administered questionnaire. Nurses with
      more experience were more knowledgeable about almost all physical assessment
      skills. Fourteen of the physical assessment skills were used more often by
      respondents with more experience in nursing practise. Ten of the physical
      assessment skills were cited as more difficult to carry out by respondents with
      less experience in nursing. The group with more clinical practise experience had
      more knowledge of physical assessment skills, used the skills more frequently and
      had less difficulty in using them. The results of this study indicated that
      Japanese nurses learn physical assessment skills 'on the job'.

PMID- 11989442
TI  - Data for nine autosomal STRs markers (CSF1PO, D13S31, D16S539, D7S820, F13A01,
      FESFPS, TH01, vWA, TPOX) from Venezuela.
AB  - Allele frequencies for nine autosomal STRs loci were obtained from individuals
      from a sample of unrelated individuals born in Venezuela.

PMID- 11989443
TI  - Polymorphisms of eight STR loci in Chinese and African (Xhosa)populations.
AB  - Allele frequencies for eight short tandem repeal loci (D16S539, D7S820, D13S317,
      D5S818, CSF1PO, TPOX, TH01 and vWA) were obtained from samples of 100 Chinese and
      96 African (Xhosa) unrelated individuals.

PMID- 11989444
TI  - Genetic profile of the Madeira Archipelago population using the new PowerPlex16
      System kit.
AB  - Allele and haplotype frequencies of 17 chromosome STR loci, 15 of them included
      in the kit PowerPlex 16 System from Promega, were determined in a sample of
      unrelated males from Madeira and Porto Santo Islands. PowerPlex 16 includes STRs
      not studied before in the Madeira population. The-kit includes two new allele
      markers (Penta D and Penta E), which proved to be extremely useful for paternity
      testing (PD = 0.952 and 0.977, respectively). The study revealed that the Madeira
      population does not differ from that of the north Portugal. Nevertheless, some
      loci presented alleles found in sub-Saharan and North European populations which
      were not reported so far in Portugal.

PMID- 11989445
TI  - Another one bites the dust.

PMID- 11989446
TI  - Does my professional role take priority over my personal life?

PMID- 11989447
TI  - How to manage--Part 5. Making presentations.

PMID- 11989448
TI  - Have family-friendly policies gone too far?

PMID- 11989449
TI  - Mentor arithmetic.

PMID- 11989450
TI  - Thwarting kidney disease. Early diagnosis is key, so if you're at risk, make sure
      your doctor regularly tests your blood and urine for signs of kidney problems.

PMID- 11989451
TI  - I manage my type 2 diabetes with lifestyle modifications and noninsulin blood
      sugar-controlling medications. I know I should avoid regular soft drinks, but
      would diet drinks or carbonated water be OK for me?

PMID- 11989452
TI  - How is adult stuttering usually treated?

PMID- 11989453
TI  - Smoking: tools for quitting. One-third of American smokers try to quit each year,
      but few take advantage of effective smoking-cessation aids.

PMID- 11989454
TI  - Homocysteine may raise Alzheimer's risk. Keep homocysteine levels in check by
      getting enough folic acid in your diet.

PMID- 11989455
TI  - To scan or not to scan? High-tech health screening is coming to a neighborhood
      near you--but is it worthwhile?

PMID- 11989456
TI  - Can sleep possibly be bad?

PMID- 11989457
TI  - Preventing type 2 diabetes: lifestyle changes work better than drugs.

PMID- 11989458
TI  - The power of negative thinking.

PMID- 11989459
TI  - Polycystic ovary syndrome may raise heart disease risk.

PMID- 11989460
TI  - Speeding up heart rate may reduce sleep apnea.

PMID- 11989461
TI  - Radio waves can retune racing hearts.

PMID- 11989463
TI  - Magnetic stimulation treats severe depression.

PMID- 11989462
TI  - Artificial tanning raises your skin cancer risk.

PMID- 11989465
TI  - Tips for the savvy supplement user.

PMID- 11989464
TI  - Genital herpes: a hidden epidemic.

PMID- 11989466
TI  - Saving your sight. Early detection is critical.

PMID- 11989467
TI  - Living with leukemia.

PMID- 11989468
TI  - FDA approves first wearable defibrillator.

PMID- 11989469
TI  - Investigators' reports. The Mexican connection.

PMID- 11989470
TI  - Expanded use of brain implant for Parkinson's disease.

PMID- 11989471
TI  - FDA approves synthetic blood thinner.

PMID- 11989472
TI  - 'Dietary supplement' warning.

PMID- 11989473
TI  - Getting tested for herpes.

PMID- 11989474
TI  - Medication approved to treat rare lung disorder.

PMID- 11989475
TI  - FDA, VA collaborate on HIV drug effects.

PMID- 11989476
TI  - Drug to treat rare pediatric liver disease.

PMID- 11989478
TI  - Overweight, obesity threaten U.S. health gains.

PMID- 11989477
TI  - New Gleevec treatment approved.

PMID- 11989479
TI  - New devices treat heart defects.

PMID- 11989480
TI  - Unilateral angiofibromas. An oligosymptomatic and segmentary form of tuberous
      sclerosis.

PMID- 11989481
TI  - Pigmented and reticulated plaques of folds. A case of lichen planus pigmentosus
      inversus?

PMID- 11989482
TI  - Fine structure of the female genital system in phytoseiid mites with remarks on
      egg nutrimentary development, sperm-access system, sperm transfer, and
      capacitation (Acari, Gamasida, Phytoseiidae).
AB  - The fine structure of the female genital system is described in two phytoseiid
      species: Phytoseiulus persimilis Athias-Henriot (mating females) and Typhlodromus
      rhenanoides Athias-Henriot (overwintering females). The female genital tract is
      composed of an unpaired gonad, the uterus (oviduct I), and the vaginal duct
      (oviduct II). The latter leads to the vagina (genital atrium), into which a pair
      of vaginal glands opens. The gonad (ovary s.l.) has two components: the ovary
      (s.str) where germ cells develop and the lyrate organ serving as a nutrimentary
      compartment. In the ovary (s.str.), somacells and germ cells are observed. The
      germ cells surround a central tissue, to which they have direct contact with a
      nutritive cord at least in the previtellogenic phase during oogenesis. In
      fertilized females, cells likely representing capacitated sperm cells are also
      found in the ovary. The lyrate organ has two arms that extend anteriorly but join
      in their posterior part in front of the ovary (s.str.). The lyrate organ is
      composed of a somatic (supporting) and a nutritive tissue. The nutritive tissue,
      which is a syncytium, is continuous with the central tissue. The uterus starts
      from the ventral region of the central tissue. Finally, the ultrastructure of the
      sperm-access system, composed of paired solenostomes, major and minor ducts,
      emboli, calyces, and vesicles, is reported and functional aspects are discussed.
      The minor ducts end in the somatic tissue of the ovary s.str. However, because of
      its extremely reduced lumen and the peculiar morphology of its beginning, it
      seems unlikely that the minor duct lumen serves as a simple route for the sperm
      towards the ovary.

PMID- 11989483
TI  - The role of cuticular compounds in the resistance of honey bees (Apis mellifera)
      to tracheal mites (Acarapis woodi).
AB  - This study examined the migration of tracheal mites (Acarapis woodi) into honey
      bees (Apis mellifera) from different colonies and the relative attraction of
      mites to hexane extracts from the external body surfaces of young bees. Relative
      resistance of bees from different colonies initially was assessed with a field
      bioassay that involved tagging newly emerged bees, pooling them in heavily mite
      infested colonies, retrieving them 7 days later, and examining them for tracheal
      mite prevalence and abundance. For those colonies identified as most resistant
      and least resistant, cuticular chemicals were extracted in hexane from frozen,
      newly emerged worker bees. These extracts were presented to individual tracheal
      mites in pairwise fashion in a laboratory bioassay. The results demonstrated that
      mites prefer extracts of bees from some colonies more than others, however, no
      consistent differences were demonstrated. Our inability to predict mite responses
      to extracts based on our initial assessment of relative resistance indicates that
      other mechanisms of resistance influence mite success in colonizing new host
      bees.

PMID- 11989484
TI  - Developmental time of Blattisocius tarsalis (Acari: Ascidae) at different
      temperatures.
AB  - The developmental time of the predatory mite Blattisocius tarsalis (Berlese)
      (Acari: Ascidae) was investigated at temperatures of 15, 21 and 25 degrees C and
      75% r.h. Eggs 1-3 days old of Ephestia kuehniella Zeller (Lep.: Pyralidae),
      killed by freezing, were used as food. Mean developmental times were found to be
      22.4, 8.5 and 7.0 days, respectively. Within the investigated thermal limits the
      developmental rate showed a linear relationship with temperature and the
      corresponding thermal threshold for development was calculated to 10.2 degrees C.

PMID- 11989485
TI  - Attraction to orange: sexiness, not gluttony.

PMID- 11989486
TI  - Tree-ring chronologies and climate variability.

PMID- 11989487
TI  - Scenarios which may lead to the rise of an asteroid-based technical civilisation.
AB  - In a previous paper, the author described a hypothetical development path of
      technical civilisations which has the following stages: planet dwellers, asteroid
      dwellers, interstellar travellers, interstellar space dwellers. In this paper,
      several scenarios are described which may cause the rise of an asteroid-based
      technical civilisation. Before such a transition may take place, certain space
      technologies must be developed fully (now these exist only in very preliminary
      forms): closed-cycle biological life support systems, space manufacturing
      systems, electrical propulsion systems. After mastering these technologies,
      certain events may provide the necessary financial means and social impetus for
      the foundation of the first asteroid-based colonies. In the first scenario, a
      rich minority group becomes persecuted and they decide to leave the Earth. In the
      second scenario, a "cold war"-like situation exists and the leaders of the
      superpowers order the creation of asteroid-based colonies to show off their
      empires' technological (and financial) grandiosity. In the third scenario, the
      basic situation is similar to the second one, but in this case the asteroids are
      not just occupied by the colonists. With several decades of hard work, an
      asteroid can be turned into a kinetic energy weapon which can provide the same
      (or greater) threat as the nuclear arsenal of a present superpower. In the fourth
      scenario, some military asteroids are moved to Earth-centred orbits and utilised
      as "solar power satellites" (SPS). This would be a quite economical solution
      because a "military asteroid" already contains most of the important components
      of an SPS (large solar collector arrays, power distribution devices, orbit
      modifying rocket engine), one should add only a large microwave transmitter.

PMID- 11989488
TI  - Neutron yields from 155 MeV/nucleon carbon and helium stopping in aluminum.
AB  - Neutron fluences have been measured from 155 MeV/nucleon 4He and 12C ions
      stopping in an Al target at laboratory angles between 10 and 160 deg. The
      resultant spectra were integrated over angle and energy above 10 MeV to produce
      total neutron yields. Comparison of the two systems shows that approximately two
      times as many neutrons are produced from 155 MeV/nucleon 4He stopping in Al and
      155 MeV/nucleon 12C stopping in Al. Using an energy-dependent geometric cross
      section formula to calculate the expected number of primary nuclear interactions
      shows that the 12C + Al system has, within uncertainties, the same number of
      neutrons per interaction (0.99 +/- 0.03) as does the 4He + Al system (1.02 +/-
      0.04), despite the fact that 12C has three times as many neutrons as does 4He.
      Energy and angular distributions for both systems are also reported. No major
      differences can be seen between the two systems in those distributions, except
      for the overall magnitude. Where possible, the 4He + Al spectra are compared with
      previously measured spectra from 160 and 177.5 MeV/nucleon 4He interactions in a
      variety of stopping targets. The reported spectra are consistent with previously
      measured spectra. The data were acquired to provide data applicable to problems
      dealing with the determination of the radiation risk to humans engaged in long
      term missions in space; however, the data are also of interest for issues related
      to the determination of the radiation environment in high-altitude flight, with
      shielding at high-energy heavy-ion accelerators and with doses delivered outside
      tumor sites treated with high-energy hadronic beams.

PMID- 11989490
TI  - Transient synovitis: is there a need to aspirate hip joint effusions?
AB  - There is debate as to the optimal management of children with hip joint effusions
      especially regarding the decision to aspirate. The objective of this study was to
      determine whether there is a need to aspirate hip joint effusions detected on
      ultrasound in patients with clinical transient synovitis (TS) and to identify the
      natural history of these effusions. Twenty-five children with proven hip joint
      effusions were followed up sequentially by clinical and radiological examination
      until symptom free. The mean age was 6 years with equal right/left distribution.
      No child underwent hip aspiration and no cases of sepsis were missed. The median
      size of hip effusion detected on ultrasound at presentation was 9 mm. At 7 days
      60% (15/25) of patients had a normal clinical examination with no detectable
      effusion on ultrasound. At 14 days 16% (4/25) had an effusion detectable on
      ultrasound but they were all pain and limp free and their effusions were reducing
      in size. These results support the known benign nature of TS and that it will
      settle with conservative treatment.

PMID- 11989489
TI  - Sucrose regulation of ADP-glucose pyrophosphorylase subunit genes transcript
      levels in leaves and fruits.
AB  - ADP-glucose pyrophosphorylase (AGPase, EC2.7.7.27) is a key regulatory enzyme in
      starch biosynthesis. The enzyme is a heterotetramer with two S and two B
      subunits. In tomato, there are three multiple forms of the S subunit gene. Agp
      S1, S2 and B are highly expressed in fruit from 10 to 25 days after anthesis. Agp
      S3 is only weakly expressed in fruit. Sucrose significantly elevates expression
      of Agp S1, S2 and B in both leaves and fruits. Agp S1 exhibits the highest degree
      of regulation by sucrose. In fact, sucrose may be required for Agp S1 expression.
      For excised leaves incubated in water, no transcripts for Agp S1 could be
      detected in the absence of sucrose, whereas it took up to 16 h in water before
      transcripts were no longer detectable for Agp S2 and B. Neither Agp S3 nor the
      tubulin gene is affected by sucrose, demonstrating that this response is
      specifically regulated by a carbohydrate metabolic signal, and is not due to a
      general increase in metabolism caused by sucrose treatment. Truncated versions of
      the promoter for Agp S1 indicate that a specific region 1.3-3.0 kb upstream from
      the transcription site is responsible for sucrose sensitivity. This region of the
      S1 promoter contains several cis-acting elements present in the promoters of
      other genes that are also regulated by sucrose.

PMID- 11989491
TI  - High survival in out-of-hospital cardiopulmonary resuscitation--7 years'
      incidence according to the Utstein template in a small town in Northern Norway.
AB  - Core data according to the Utstein template was compiled from all out-of-hospital
      resuscitations in the city of Bodo, Northern Norway, over 7 years (1992-98). Out
      of a population of 34,500, 149 resuscitations were attempted. A cardiac aetiology
      was present in 123 patients and their median age was 72.1 years. Eighteen of the
      96 patients having suffered a witnessed arrest of cardiac origin were alive after
      1 year (18.8%). Fifteen had the best cerebral performance score (scale 1-5) and
      three had a score of 2. Survival among all resuscitated patients (149) was 18.8%
      also, giving a number of 62 attempted resuscitations and 11.2 survivors per
      100,000 inhabitants per year, respectively. Thirty-three per cent of witnessed
      cardiac arrests with ventricular fibrillation or ventricular tachycardia survived
      to discharge, but only 7% with asystole. When the arrest was witnessed, median
      response time was 5 minutes, and was 3 minutes for the survivors. To our
      knowledge, this is the highest survival of out-of-hospital arrests in Scandinavia
      reported so far, and is chiefly explained by short turnout distances.

PMID- 11989492
TI  - Chest pain in the emergency department: the broad spectrum of causes.
AB  - We performed a prospective study to describe the broad spectrum of causes of
      chest pain in patients presenting to the emergency department and to compare the
      diagnoses in referred patients, self-referred patients and patients rushed in by
      ambulance. The final diagnosis in a consecutive case series of 578 chest pain
      patients was established after discharge from the hospital. The underlying
      disorders were grouped into cardiac, respiratory, gastro-oesophageal disorders,
      musculoskeletal pathology, somatization disorders, other diseases and unknown.
      For comparison of the frequencies of the disease categories the Chi-squared test
      was used. Out of 578 patients, 161 (27.9%) were self-referred, 369 (63.8%) were
      referred by the general practitioner and 48 (8.3%) were rushed in by ambulance.
      Cardiac diseases represented 51.7% of the cases, myocardial infarction and
      unstable angina 19% and 12.8% respectively Cardiac diseases were statistically
      significantly less common in self-referred patients (p<0.0005). Pulmonary
      diseases encompassed 14.2% of the population, followed by somatization disorders
      (9.2%), musculoskeletal pathology (7.1%) and other causes (4.3%). In 11.1% of the
      cases no definite final diagnosis could be established. Somatization disorders
      were significantly more frequent in self-referred and ambulance patients. Cardiac
      and pulmonary problems are the most frequent underlying disorders in acute chest
      pain patients in the emergency department. Somatization disorders and
      musculoskeletal pathology represented respectively 19.1% and 14.8% of the non
      cardiac causes. The referral pattern influenced significantly the distribution of
      the disease categories with more cardiac and less psychiatric disorders in
      referred patients.

PMID- 11989494
TI  - Effect of the initiation of noninvasive bi-level positive airway pressure on
      haemodynamic stability.
AB  - Noninvasive ventilation using noninvasive bilevel positive airway pressure (Bi
      PAP) has been shown to be an effective means of improving oxygenation and
      respiratory status in patients with obstructive pulmonary disease (COPD) and
      acute congestive heart failure (CHF). However, it is uncertain what effects this
      positive airway pressure has on the haemodynamic condition of these patients.
      This study examines the acute changes in basic circulatory parameters with the
      initiation of Bi-PAP. Noninvasive measurements of the heart rate, systolic and
      diastolic arterial pressure, cardiac index, total peripheral resistance,
      ventricular ejection time, and total diastolic time were determined by impedance
      cardiography before and after the institution of Bi-PAP (pressures 15/5) in a
      group of healthy volunteers. In a collateral study, the same measurements were
      made in COPD patients in whom Bi-PAP was initiated for therapeutic reasons.
      Changes in the haemodynamic parameters were analysed using a paired t-test (p <
      0.05). In the 12 healthy volunteers studied there were no significant differences
      in any of the haemodynamic parameters measured (average cardiac index: 2.75 +/-
      0.78) over a period of 15 minutes after the placement of Bi-PAP. Similar results
      for most haemodynamic parameters were found in the 7 COPD patients with imminent
      respiratory failure (average respiratory rate 24.8 +/- 3.2) when Bi-PAP was
      utilized with the exception of significant but small increases in the cardiac
      index, stroke volume and oxygen saturation (p<0.05). While Bi-PAP is frequently
      used in the treatment of patients with acute respiratory failure, little is known
      about its effect on haemodynamics. This study suggests that the effects of the
      initiation of Bi-PAP on the general circulation and cardiac output may be of
      minor relevance.

PMID- 11989493
TI  - Chest pain unit management of patients at low and not low-risk for coronary
      artery disease in the emergency department. A 5-year experience in the Florence
      area.
AB  - In this study, we screened a total of 6723 consecutive patients with chest pain
      and ECG non-diagnostic for acute myocardial infarction (AMI) on presentation to
      the emergency department (ED). The aim of the study was to avoid missed AMI,
      improve safe early discharge and reduce inappropriate coronary care unit (CCU)
      admission. Chest pain patients were triaged using a clinical chest pain score and
      managed in a chest pain unit (CPU). Patients with a low clinical chest pain score
      were considered at very 'low-risk' for cardiovascular events and discharged from
      the ED; patients with a high chest pain score were submitted to CPU management.
      Observation and titration of serum markers of myocardial injury were obtained up
      to 6 hours. Rest or stress myocardial scintigraphy (SPECT) was performed in
      patients > 40 years or with > or = 2 major coronary risk factors. Exercise
      Tolerance Test (ETT) or Stress-Echocardiogram (stress-Echo) were performed in
      younger patients or with < 2 coronary risk factor, or unable to exercise,
      respectively We discharged directly from the ED the majority of patients (4454;
      66%): in this group there was only a 0.2% final diagnosis of coronary artery
      disease (CAD) at follow-up. The remaining 34% of patients, with non-diagnostic or
      normal ECG, were managed in the CPU. In this group, 1487 patients (representing
      22% of the overall study group) were found positive for CAD, two-thirds because
      of delayed ECG or serum markers of myocardial injury, and one-third by Echo,
      SPECT or ETT. In conclusion, CPU based management allowed 22% early detection of
      myocardial ischaemia and 78% early discharge from the ED avoiding inappropriate
      CCU admission and optimizing the use of urgent angiography.

PMID- 11989495
TI  - P-R segment depression: an early diagnostic feature in acute pericarditis: a
      telephone survey of UK accident and emergency departments.
AB  - P-R segment depression is an early ECG change in the evolution of acute
      pericarditis. This is widely recognized in the USA and appears in several major
      emergency medicine texts. A telephone survey was conducted to gain an overview of
      the knowledge of accident and emergency career doctors in the UK. We hope to use
      the results to highlight this potentially useful sign. One hundred accident and
      emergency departments, listed in the 1999 British Association for Accident and
      Emergency Medicine as seeing more than 40,000 new patients per year, were
      contacted in a telephone survey. The registrar, staff grade or consultant on call
      was asked to respond to a brief questionnaire. One hundred accident and emergency
      (A&E) specialist doctors were contacted--60 specialist registrars, 23 consultants
      and 17 staff grades. Of those questioned, 24% had a background in general
      medicine. The remainder had trained in surgery, A&E medicine or anaesthetics.
      None of the doctors questioned volunteered knowledge of P-R depression when asked
      an open question. Six doctors (6%) admitted, when prompted, to having previously
      heard of this sign. Knowledge of P-R segment depression is not widespread amongst
      UK A&E specialists. It is a potentially useful early electrocardiogram change in
      the evolution of acute pericarditis. Its recognition may aid diagnosis and
      prevent the inappropriate administration of thrombolytic therapy.

PMID- 11989496
TI  - Correlation between injuries sustained in the A17 coach accident and the seating
      location.
AB  - Road traffic accidents where coaches are involved are increasing. Having been
      confronted with a similar incident giving rise to the deployment of the medical
      disaster plan of West Flanders, we have been looking for particular mechanisms to
      explain the passengers' injuries. We identified some technical aspects (e.g. foot
      bars) to consider when safety precautions have to be taken.

PMID- 11989497
TI  - Use of analgesia in a paediatric accident and emergency department following limb
      trauma.
AB  - The objective of this study was to assess analgesic use and the use of a pain
      scoring system on those children presenting to a paediatric accident and
      emergency (A&E) department with a history of injury due to trauma. A random
      sample of patients who presented to a paediatric A&E department over a 6-week
      period with a history of limb trauma were prospectively studied. Pain severity
      scores were assessed on arrival and at 10, 30 and 60 minutes using the Douhit
      Faces Scale and any analgesia given or plaster application was noted. One hundred
      and seventy-two patients were studied. The median age was 10 years (range 3-13
      years) and the majority, 56%, were male. The mean initial pain scores were 2.7
      (range 1-4) for boys and 3.0 (range 1-4) for girls. The presenting injuries were
      103 upper or lower limb fractures and 69 'soft tissue' injuries. Only 84 (49%)
      patients received analgesic medication in the department (30% morphine; 70%
      paracetamol); analgesia was not given to the remaining 88 (51%). Of these, 7
      declined analgesia, and 5 had already taken analgesia on arrival to A&E. Despite
      prompt triage (median time 2 minutes, range 0-10 minutes), the median time from
      arrival to paracetamol administration was 20 minutes (range 4-105 minutes) and
      for morphine was 14 minutes (range 2-57 minutes). Pain is a common symptom in
      patients presenting to A&E. Because children's pain can be particularly difficult
      to assess, a pain scoring system such as the Douhit Faces Scale can be a useful
      means of pain assessment in the A&E setting. Despite increased awareness, pain is
      still under treated in the A&E department.

PMID- 11989498
TI  - Transcutaneous and intra-arterial blood gas monitoring--a comparison during
      apnoea testing for the determination of brain death.
AB  - Intra-arterial (i.a.) and transcutaneous (t.c.) blood gas monitoring were
      compared with in vitro blood gas analysis (abg) during apnoea testing for the
      determination of brain death in a prospective observational study. All three
      methods were used simultaneously in 19 patients in whom brain death was
      suspected. Brain death was confirmed in each case adhering to the recommendations
      of the Scientific Advisory Board of the German Federal Chamber of Physicians
      which demand a PCO2 of at least 60 mmHg. In vitro parameters ranged from 23.2 to
      80.4 mmHg (PCO2), 52.7 to 509.9 mmHg (PO2), and 7.072 to 7.591 (pH). The intra
      individual correlations between both monitoring methods (rPCO2=0.958, rPO2=0.859)
      and between each of them and abg (r>0.960) were high. Absolute deviations from
      abg for the corrected as well as uncorrected measurements were similar for both
      methods, except with regard to group bias where an advantage for the i.a. values
      emerged. Since many of the i.a. measurements failed and the disposable i.a.
      probes cost much more than the t.c. electrodes, the i.a. technique at present
      holds no advantage over t.c. measurements in testing for apnoea in suspected
      brain death except where simultaneous monitoring of pH and temperature are
      desired.

PMID- 11989499
TI  - Acute methylene chloride intoxication--a case report on domestic poisoning.
AB  - Acute intoxication by methylene chloride has primarily been reported from
      occupational settings. However, it may occur through domestic exposure, by the
      use of aerosol sprays, degreasers and paint removers. We describe an unusual case
      of an accidental domestic methylene chloride intoxication through the use of
      aerosol spray, resulting in an HbCO of 30%.

PMID- 11989500
TI  - Intravaginal vibrator of long duration.
AB  - Intravaginal foreign bodies of long duration are a rare entity and are seen in
      the practice of Obstetrics and Gynaecology, but patients may present to the
      Accident and Emergency department for their removal. Various bizarre objects have
      been inserted into the vagina and many patients are too embarrassed and will wait
      and try to remove them themselves rather than seek medical advice. Vaginal
      foreign bodies of long duration may be complicated by fistulas and such patients
      should be referred to the gynaecologist.

PMID- 11989501
TI  - Efficacy of long duration resuscitation and magnesium sulphate treatment in
      amitriptyline poisoning.
AB  - A single dose of cyclic antidepressants leads to death in childhood. Myocardial
      depression and ventricular arrhythmia are the severe side effects in cyclic
      antidepressant overdose. A 23-month-old boy was brought to hospital because 36
      mg/kg of amitriptyline had been taken. Cardiopulmonary resuscitation was applied
      for 70 minutes due to cardiac and respiratory arrest. Circulation was restored
      after resuscitative efforts. However, ventricular tachycardia was detected which
      did not respond to lidocaine, bicarbonate and cardioversion treatment. Magnesium
      sulphate treatment was started and cardiac rhythm normalized. No side effects
      were observed. The duration of resuscitation should be extended in cases of
      cardiopulmonary arrest secondary to tricyclic antidepressants intoxication. It
      should be continued at least for 1 hour. Magnesium sulphate was found to be
      extremely effective in a case of amitriptyline intoxication refractory to
      treatment.

PMID- 11989502
TI  - Superior mesenteric vein thrombosis presented transient false positivity for
      lupus anticoagulant under heparin treatment.
AB  - A 24-year-old Japanese man was admitted because of massive haematemesis and
      melaena with persistent abdominal pain. Markedly bloody ascites and severely
      oedematous small intestine were recognized, and angiography then revealed
      superior mesenteric vein thrombosis. After resection of the necrotic small
      intestine, continuous intravenous infusion of heparin and urokinase was
      performed. This patient had no familial or personal history of thrombosis. On the
      15th day after operation, an initial search for lupus anticoagulant revealed that
      the prothrombin time (PT) ratio and dilute activated partial thromboplastin time
      (aPTT) were positive under heparin treatment, without evidence of rheumatic or
      connective tissue disease. Thrombocytopenia was observed with a nearly
      normocellular bone marrow. A follow-up examination 1 year later still revealed an
      increased aPTT. However, all tests for antiphospholipid antibodies had been
      negative including dilute aPTT for about 2 years since the 15th day after
      operation. These findings suggest that, in this patient, superior mesenteric vein
      thrombosis has not been associated with primary antiphospholipid syndrome but is
      probably idiopathic. Positive tests for lupus anticoagulant in the initial period
      may be unreliable due to heparin treatment.

PMID- 11989503
TI  - Results of treatment of the extensive volar wrist lacerations: 'the spaghetti
      wrist'.
AB  - 'Spaghetti wrist' describes a volar wrist laceration in which at least 10
      structures, inclusive of tendons, at least one major nerve and usually one major
      vessel are divided. This retrospective study, was performed between January 1990
      and December 1995 at the Department of Orthopaedic and Traumatology of Erciyes
      University Medical School. The outcome of 21 patients who sustained simultaneous
      laceration of the median and ulnar nerves as well as flexor tendons at the wrist
      is described. The mean follow-up was 6.4 years. The flexor tendons were assessed
      using criteria from Lister et al. Vascular status was assessed clinically. Ulnar
      and median nerve repair results at the final control were assessed according to
      Seddon's criteria. Furthermore, the ulnar nerve was assessed according to the
      power of the first dorsal interosseous muscle, and the median nerve assessed by
      the function of abductor pollicis brevis and sensory function modality. Primary
      nerve repair yielded satisfactory results, the median nerve repair achieving a
      better outcome than the ulnar nerve. Most patients regained a functional range of
      wrist movement at the final control.

PMID- 11989504
TI  - UEFA Champions League: does live television football affect attendances at
      accident and emergency departments? Union of European Football Associations.

PMID- 11989505
TI  - How to manage the ED crisis when hospital and/or ED capacity is reaching its
      limits. Report about the implementation of particular interventions during the
      Christmas crisis.

PMID- 11989506
TI  - Controversies in the development of emergency medicine as a primary specialty.

PMID- 11989507
TI  - Patients' rights and emergency medical treatment: an emerging right to emergency
      care?

PMID- 11989508
TI  - Epidemiology of poisoning in children: a 7-year survey in a paediatric emergency
      care unit.
AB  - Acute poisoning in children is still a major public health problem, and
      represents a frequent cause of admission in emergency departments. We carried out
      an epidemiological study of poisonings leading to admission to a paediatric
      emergency care unit (PECU). We analysed data from 2988 children who were admitted
      to the PECU of Bordeaux, France with acute poisoning from 1989 through 1995.
      During the 7-year period, the poison exposure numbers decreased slightly from 490
      to 382 (6% vs. 3% of total medical emergencies). This represented a mean annual
      incidence of 1.4 poison exposures per 1000 children younger than 18 years of age
      and living in Bordeaux and its surroundings. Characteristics of the study
      population, circumstances of poisoning and substances involved were similar to
      those previously described. Eighty per cent of children were younger than 5 years
      of age, presented with a benign course. Forty per cent were not treated and 75%
      were discharged home either immediately or within 24 hours of admission. Only
      1.5% of cases, mainly adolescent girls who attempted suicide, were admitted to a
      paediatric intensive care unit. Overall mortality rate was 0.33/1000. In
      children, most cases of acute poisoning are accidental, benign, and mainly
      attributed to the ingestion of a non-toxic substance. This points to the need for
      better information of the population on availability of poison control centre
      calling facilities, in order to decrease the number of admissions to the PECU.
      Patients suspected of having ingested a potentially dangerous substance can be
      managed in short-stay observation units, thus avoiding unnecessarily prolonged
      hospitalization. Acute poisoning in children remains a frequent problem,
      highlighting the need to develop an education programme on primary prevention in
      our region.

PMID- 11989509
TI  - Networks for research: the power of one plus one plus one.
AB  - Networks for emergency medicine research are both powerful and practical, and can
      be run on a very low budget. The keys to making them work are relevant questions,
      achievable goals, recognition of contributions, coordination, feedback and
      leadership. Many hands do really make the work light!

PMID- 11989510
TI  - More on endplate noise.

PMID- 11989511
TI  - Low-volume exercise rehabilitation improves functional capacity and self-reported
      functional status of dialysis patients.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of a program of
      low-volume exercise rehabilitation on the functional capacity and self-reported
      functional status of nonanemic dialysis patients. DESIGN: This was a controlled
      study in a clinical setting with a repeated measures design. Functional capacity
      and functional status were assessed before and after 12 wk of exercise
      rehabilitation or 12 wk of normal activity for two groups of dialysis patients.
      RESULTS: Mixed-model repeated measures analysis of variance revealed significant
      group by time interactions characterized by improvements for the exercise
      rehabilitation group alone in total walk, stair-climb, and stair-descent times of
      15+/-5.8%, 22+/-11%, and 18+/-12% respectively. Self-reported walking speed,
      walking impairment-leg weakness, and walking impairment-shortness of breath were
      also observed to improve significantly for the exercise rehabilitation group
      alone by 15+/-13%, 25+/-11%, and 28+/-16%, respectively. CONCLUSION: Low-volume
      exercise rehabilitation can improve activity of daily living-related functional
      capacity and self-reported functional status of nonanemic dialysis patients.

PMID- 11989512
TI  - The FIM instrument in the United States and Italy: a comparative study.
AB  - OBJECTIVE: To compare FIM instrument ratings between Italy and the United States.
      DESIGN: This study utilized 169,835 United States and 4,536 Italian FIM
      instrument records for stroke with the left side of the body affected, stroke
      with the right side of the body affected, and orthopedic conditions. RESULTS:
      Case-mix, patient age, and admission and discharge FIM instrument scores were
      similar. The delays between onset of disability and admission to rehabilitation
      and lengths of stay in rehabilitation were 2-4 times longer in Italy. In Italy,
      some 88-95% of the subjects were discharged to the community vs. 74-88% in the
      United States. Hierarchies of FIM instrument ratings across the motor and
      cognitive items were similar, but there were interesting differences. The
      hierarchical patterns showed that dressing, bathing, perineal hygiene, and tub or
      shower transfer were relatively more difficult in Italy compared with the Unites
      States, whereas walking was easier in Italy compared to the United States.
      CONCLUSION: The Italian health care payment system offers less incentive for
      early discharges from acute care and rehabilitation. In Italy, nursing homes are
      less accessible, whereas family support is more available. Apparently less
      intensive treatment is applied in Italy, where a minimum time per day for
      rehabilitation services is not mandatory for payment. Occupational therapy is not
      used in Italy and the focus is more on physical therapy.

PMID- 11989513
TI  - Motor control impairment of the contralateral wrist in patients with unilateral
      chronic wrist pain.
AB  - OBJECTIVE: Assessment of the quality of fine motor control in patients with
      unilateral chronic wrist pain seldom focuses on the possibility that control of
      movements is effector independent at the cerebral level. This mechanism may be
      involved in an impairment of motor function in the unaffected wrist. We studied
      the possible motor impairment in the unaffected wrist in patients with chronic
      wrist pain. DESIGN: Eighteen patients with chronic wrist pain in their dominant
      hand and 20 healthy controls performed, using their nondominant hand, back-and
      forth, left-to-right stroke patterns with a pen on a digital writing tablet
      connected to a computer. Fluency of movement, defined as the number of zero
      crossings of the acceleration curve (pZC), average stroke size, and average
      velocity were calculated. RESULTS: The controls moved significantly more fluently
      than the patients (pZC, 0.26+/-0.07 for controls and 0.46+/-0.20 for patients; P
      < 0.001), suggesting that long-term afferent disturbances may compromise cerebral
      motor control mechanisms. CONCLUSIONS: This result is in accordance with the view
      that chronic pain complaints may be maintained by persistently abnormal cerebral
      motor control. This finding opens a new perspective on the understanding and
      treatment of chronic wrist pain.

PMID- 11989514
TI  - Corticosteroid injection vs. nonsteroidal antiinflammatory drug and splinting in
      carpal tunnel syndrome.
AB  - OBJECTIVE: To compare the efficacy of local corticosteroid injection to a
      nonsteroidal antiinflammatory drug and splinting for the treatment of carpal
      tunnel syndrome. DESIGN: This study was a prospective, unblinded, randomized
      clinical trial with an 8-wk follow-up. Thirty-three hands of 23 patients were
      randomly treated with acemetacine and splinting (group A) or with corticosteroid
      injection (group B). Clinical (symptom severity scale, visual analog scale, Tinel
      and Phalen tests) and electromyographic evaluations were performed on initial
      visit and after 8 wk. RESULTS: Clinical and electromyographic parameters, which
      were similar at baseline, were improved in both groups after treatment.
      Improvement was also similar when both groups were compared at 8 wk. CONCLUSION:
      Both splinting combined with the use of a nonsteroidal antiinflammatory drug and
      steroid injection into the carpal tunnel resulted in significant improvement in
      carpal tunnel syndrome.

PMID- 11989515
TI  - Identification of feigned shoulder flexion weakness in normal subjects.
AB  - OBJECTIVE: The purpose of this study was to compare the effect of three related
      test protocols on the power of a specific index relating to the difference
      between the eccentric to concentric strength ratios (DEC) to identify feigned
      shoulder flexion effort. DESIGN: Seventeen normal subjects were instructed to
      exert maximal concentric and eccentric shoulder flexion effort and then to feign
      weakness, pretending the presence of a shoulder injury. RESULTS: For both range
      of motions (ROMs), the DEC scores in the feigned effort were significantly
      greater than their maximal counterparts. A case by case analysis revealed that
      the DEC correctly identified 100% of the feigned efforts when derived from the 40
      and 160 degrees/sec combination. CONCLUSIONS: The findings indicate that the DEC
      retains its efficiency even under very short muscle length variation as long as
      adequate velocity gradients are applied. Consequently, maximality of effort may
      be tested outside compromised ROMs, particularly where pain or instability denies
      the performance of a standard full ROM protocol.

PMID- 11989516
TI  - Effect of participation in physical activity on body image of amputees.
AB  - OBJECTIVE: The purpose of this study was to examine body image in individuals
      with amputations and to determine if a relationship exists between body image and
      level of participation in physical activity and sports. A secondary objective was
      to examine correlations between two body-image assessments. DESIGN: A
      nonrandomized survey was given to a convenience-volunteer sample of individuals
      of at least 18 yr of age with a lower limb amputation. RESULTS: Twenty-four
      participants were active and 32 were minimally active. Statistical significance
      was preset at P < 0.05, with a 95% confidence interval. An overall significant
      difference was found between groups on the MBSRQ and on three of the 10 MBSRQ
      subscales. Significant correlations were found between six MBSRQ subscales and
      the ABIS. CONCLUSION: A positive relationship was found between regular
      participation in physical activity and body image among lower limb amputees.

PMID- 11989517
TI  - Clinical measurement of muscle tone using a velocity-corrected modified Ashworth
      scale.
AB  - OBJECTIVE: To develop a new form of the modified Ashworth scale (MAS) for muscle
      tone assessment that combines the MAS score with the passive muscle-stretching
      velocity during the assessment of muscle tone, resulting in a measure that has
      higher intertester reliability than the MAS. DESIGN: Twenty-two volunteer
      subjects with spinal cord injuries at a tertiary care outpatient and inpatient
      spinal cord injury rehabilitation center affiliated with a university were
      recruited for this study. RESULTS: A decision tree in which V-MAS scores were
      obtained was developed. The data obtained from three independent raters, when
      adjusted by means of the V-MAS, showed an excellent interrater reliability.
      CONCLUSIONS: Results indicated that the V-MAS is a more reliable measure. In
      addition, the resulting units of the V-MAS, ranging from 0 to 1, are of the same
      form as pendulum test data. The V-MAS method is quite simple to use because the
      rater need only measure the angular range and duration of the passive movement to
      calculate average velocity during the MAS assessment in addition to the normal
      MAS rating of muscle tone.

PMID- 11989518
TI  - Radial nerve injuries from gunshot wounds and other trauma: comparison of
      electrodiagnostic findings.
AB  - OBJECTIVE: To identify the difference and similarity of radial nerve injury in
      gunshot wounds compared to blunt trauma with regard to level of injury,
      completeness of injury, and other associated nerve injury. DESIGN: This study was
      a retrospective review of electrophysiologic data performed in an
      electromyographic laboratory of a county hospital. A total of 67 consecutive
      patients had gunshot wounds or other trauma to the radial nerve during a 7-yr
      period (1992-1998). Forty patients met the criteria for this study. The radial
      nerve injury was categorized according to the level of involvement and
      completeness of injury. The relationship between the etiology, level of injury,
      completeness of injury, and other associated nerve injury was analyzed via
      Fisher's exact test. RESULT: There was no difference in the level of radial nerve
      injury, completeness of nerve injury, and associated nerve involvement between
      gunshot wound cases and blunt trauma cases. CONCLUSION: In contrast to the upper
      and lower extremity traumatic plexopathy in which differences were seen, our
      study showed that gunshot wound-induced radial nerve injury is similar to injury
      induced by other trauma in the factors measured.

PMID- 11989519
TI  - Endplate potentials are common to midfiber myofacial trigger points.
AB  - OBJECTIVES: To compare the prevalence of motor endplate potentials (noise and
      spikes) in active central myofascial trigger points, endplate zones, and taut
      bands of skeletal muscle to assess the specificity of endplate potentials to
      myofascial trigger points. DESIGN: This nonrandomized, unblinded needle
      examination of myofascial trigger points compares the prevalence of three forms
      of endplate potentials at one test site and two control sites in 11 muscles of 10
      subjects. The endplate zone was independently determined electrically. Active
      central myofascial trigger points were identified by spot tenderness in a
      palpable taut band of muscle, a local twitch response to snapping palpation, and
      the subject's recognition of pain elicited by pressure on the tender spot.
      RESULTS: Endplate noise without spikes occurred in all 11 muscles at trigger
      point sites, in four muscles at endplate zone sites outside of trigger points (P
      = 0.024), and did not occur in taut band sites outside of an endplate zone (P =
      0.000034). CONCLUSIONS: Endplate noise was significantly more prevalent in
      myofascial trigger points than in sites that were outside of a trigger point but
      still within the endplate zone. Endplate noise seems to be characteristic of, but
      is not restricted to, the region of a myofascial trigger point.

PMID- 11989520
TI  - Early assessment of post-stroke patients entering acute inpatient rehabilitation:
      utility of the WASI and HVLT-R.
AB  - OBJECTIVE: To examine the clinical utility of two brief assessment tools, the
      Wechsler Abbreviated Scale of Intelligence (WASI) and the Hopkins Verbal Learning
      Test-Revised (HVLT-R). We hypothesized that these measures would predict
      continued need for supervision and functional outcome at discharge. DESIGN: In
      this retrospective review, 44 patients with stroke who were admitted for acute
      inpatient rehabilitation were measured on five variables: WASI, HVLT-R, length of
      stay, FIM discharge scores, and need for supervision on discharge. RESULTS:
      Performance on the HVLT-R and WASI matrix reasoning subtest of the WASI was
      predictive of cognitive discharge scores on the FIM and need for supervision on
      discharge. The WASI similarities subtest was not associated with outcome.
      CONCLUSIONS: WASI matrix reasoning and HVLT-R are brief neuropsychological
      measures that are predictive of need for supervision and functional outcome in
      the acute stroke rehabilitation setting.

PMID- 11989521
TI  - Misdiagnosis of conversion disorders.
AB  - Five cases are presented describing the clinical features for which they were
      referred and admitted to a rehabilitation unit and later identified as having
      been misdiagnosed as having a conversion disorder. The diagnoses were sarcoma
      induced osteomalacia, cerebellar medulloblastoma, Huntington's chorea, transverse
      myelitis, and lower extremity dystonia. A perceived history of psychological
      difficulties, an unusual neurologic presentation, and normal initial diagnostic
      testing in a female patient were associated with a misdiagnosis of conversion
      disorders; unfortunately, these factors also characterize actual conversion
      disorders.

PMID- 11989522
TI  - Maximizing the response to Herceptin therapy through optimal use and patient
      selection.
AB  - The aggressiveness of human epidermal growth factor receptor-2 (HER2)-positive
      breast cancer and the poor prognosis of women with this disease demand the
      availability of accurate and reliable tests for HER2 status and the optimization
      of HER2-targeted therapy. The distinctive clinical pattern of HER2-positive
      breast cancer underlines the importance of testing for HER2 status and efforts
      are ongoing to validate the two major methods in use-immunohistochemistry (IHC),
      which measures cell membrane HER2 expression, and fluorescence in situ
      hybridization (FISH), which measures gene copy number. Clinical trial results
      demonstrate that there is an association between strong HER2 overexpression (IHC
      3+) and optimal response to therapy with the novel recombinant HER2 antibody
      Herceptin. High levels of concordance between IHC 3+ and FISH-positive status
      have been observed, and response to treatment with Herceptin is similar for
      patients whose breast cancers are IHC 3+ and those who are FISH-positive.
      Observations to date have led to the formulation of an algorithm for HER2 status
      determination and Herceptin use which recommends that: (i) the HER2 status of all
      women with breast cancer be determined at presentation, (ii) all IHC 3+ and FISH
      positive patients with metastatic disease should receive Herceptin, (iii)
      Herceptin should be used early in the course of metastatic breast cancer and
      preferably first line, and (iv) Herceptin therapy should be continued until
      disease progression.

PMID- 11989523
TI  - Trials of new combinations of Herceptin in metastatic breast cancer.
AB  - Herceptin extends survival in human epidermal growth factor receptor-2 (HER2)
      positive metastatic breast cancer patients when administered with paclitaxel or
      anthracycline/cyclophosphamide (AC), and the combination with 3-weekly paclitaxel
      is the current standard first-line therapy. However, other combinations may be
      equally effective. This review provides information on recent and ongoing trials
      of new Herceptin combinations. Preliminary results indicate that Herceptin plus
      epirubicin/cyclophosphamide may be effective without the cardiotoxicity of the AC
      combination. Weekly paclitaxel plus Herceptin has produced responses in 83% of
      HER2-positive patients treated. Co-administering Herceptin with other cytotoxic
      agents has also been investigated, with combination partners being chosen based
      on in vitro synergy with Herceptin, known efficacy as monotherapy and convenience
      of weekly administration (e.g. docetaxel, vinorelbine). High response rates have
      been observed in these clinical trials, e.g. up to 80% in combination with
      vinorelbine. Furthermore, Herceptin in combination with weekly paclitaxel,
      docetaxel or vinorelbine was well tolerated: there was no significant
      cardiotoxicity or unexpected toxicity and the combination showed an adverse event
      profile similar to that seen with monotherapy with the cytotoxic agent. Thus,
      Herceptin produces additional clinical benefit when added to all the cytotoxic
      agents with which it has been examined, further demonstrating its potential for
      use in HER2-positive breast cancer patients.

PMID- 11989524
TI  - Herceptin: the future in adjuvant breast cancer therapy.
AB  - New drugs for the treatment of breast cancer are generally introduced into
      clinical practice in the metastatic setting. However, it is well known that
      therapeutic response improves when drugs are used earlier in the disease.
      Therefore, once drugs have shown a major therapeutic impact in the metastatic
      setting, investigation in the adjuvant setting should be prioritized. Herceptin
      has shown significant efficacy and an ability to extend survival in human
      epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer
      patients and is well tolerated. Four major randomized, multicenter adjuvant
      clinical trials of Herceptin in patients with HER2-positive primary breast cancer
      have been started or are planned. The designs of these trials are described. With
      a total of over 12 000 patients, these studies should provide the information
      necessary to confirm the clinical potential of Herceptin as adjuvant therapy. The
      inclusion of a variety of regimens, including different durations of Herceptin
      therapy in the Herceptin Adjuvant (HERA) Trial, will allow the optimal
      therapeutic approach to be identified, and the size and generally pragmatic
      designs should encourage clinicians to enroll patients. The establishment of the
      role of Herceptin in the adjuvant setting will offer women with HER2-positive
      primary breast cancer the chance for improved survival. This is particularly
      important given that HER2-positive breast cancer patients form a high-risk group
      with a poor overall prognosis.

PMID- 11989525
TI  - Efficacy and safety of Herceptin in women with metastatic breast cancer: results
      from pivotal clinical studies.
AB  - Amplification of the human epidermal growth factor receptor-2 (HER2) gene and
      overexpression of the encoded protein are seen in 20-30% of breast cancers, and
      are associated with aggressive disease and relatively poor prognosis. Thus, HER2
      represents an appropriate target for anticancer treatment and the humanized anti
      HER2 monoclonal antibody Herceptin has been developed for this purpose. The
      efficacy of Herceptin has been confirmed in two pivotal trials-a monotherapy
      study in 222 women with HER2-positive metastatic breast cancer who had already
      received one or two chemotherapy regimens for metastatic disease and a study
      comparing Herceptin plus chemotherapy with chemotherapy alone in 469 patients
      previously untreated for metastatic disease. Herceptin monotherapy was associated
      with longer median response duration and survival than previous chemotherapy.
      Addition of Herceptin to chemotherapy increased response rates, time to disease
      progression and survival duration. Benefit was greatest in patients with high
      level HER2 overexpression. Herceptin was well tolerated, with mild to moderate
      infusion-related reactions, usually seen with the first infusion only, being the
      most common event. Most patients respond to conventional supportive treatment.
      Cardiotoxicity, the most serious adverse event observed, occurred mainly in
      patients exposed to anthracyclines and was generally manageable. Thus, Herceptin
      represents a significant development in the management of HER2-positive breast
      cancer.

PMID- 11989526
TI  - Inter-observer concordance in grading retinopathy in cerebral malaria.

PMID- 11989527
TI  - Failure of chloroquine therapy in a splenectomized child infected with Plasmodium
      vivax.

PMID- 11989528
TI  - Multicentre study, in patients with imported malaria, on the sensitivity and
      specificity of a dipstick test (ICT Malaria P.f./P.v.) compared with expert
      microscopy.
AB  - A prospective, multicentre study was carried out in Italy to assess the
      sensitivity and specificity of a rapid dipstick test (ICT Malaria P.f./P.v.) in
      the diagnosis of imported malaria caused by Plasmodium falciparum and other
      Plasmodium spp. The test is based on the detection of histidine-rich protein-2
      (HRP-2) from P. falciparum and 'panmalarial' antigen in peripheral blood. The 241
      subjects were international travellers or immigrants from areas where malaria is
      endemic. When compared with the microscopical examination of bloodsmears (used as
      the 'gold standard'), the dipsticks were found to be 94.4% sensitive and 94.5%
      specific for pure infections with P. falciparum. The performance of the tests
      when used on patients infected with species other than P. falciparum or more than
      one Plasmodium spp. showed a high degree of variability. Although the dipsticks
      represent a very simple, rapid, and valuable diagnostic aid, they should not be
      considered a complete substitute for direct microscopical diagnosis using stained
      bloodsmears.

PMID- 11989529
TI  - Immunochromatographic strip-test detection of anti-K39 antibody in Indian
      visceral leishmaniasis.
AB  - Stored sera from 429 Indian subjects were assayed to extend the analysis of the
      accuracy of immunochromatographic strip-test detection of anti-K39 antibody in
      the non-invasive diagnosis of visceral leishmaniasis (VL). All 225 samples from
      patients with proven Leishmania infection tested positive [estimated sensitivity
      = 100%; 95% confidence interval (CI)=98%-100%]. Sera from 99 of the 100
      symptomatic patients with other diseases were non-reactive (estimated specificity
      = 99%; CI = 94%-100%). However, samples from 13 of the 104 apparently healthy
      controls showed positive strip-test results (estimated specificity = 88%; CI =
      79%-93%), yielding an overall specificity of 93% (190/204; CI = 88%-96%). If
      applied in a practical clinical setting (on symptomatic patients in whom active
      VL is suspected and other common infections have been excluded), strip testing of
      serum for anti-K39 antibody should be both sensitive and specific for diagnosing
      VL in India.

PMID- 11989530
TI  - The performance of direct agglutination tests (DAT) in the diagnosis of visceral
      leishmaniasis among Ethiopian patients with HIV co-infection.
AB  - The incidence of visceral leishmaniasis (VL) in Ethiopia has dramatically
      increased over the last 10 years, coinciding with the advent of the HIV epidemic.
      HIV co-infection in VL patients results in atypical, clinical and serological
      presentations, and may hamper serological diagnosis of VL. The performance of
      direct agglutination tests (DAT) in the diagnosis of VL in 103 Ethiopian patients
      with or without HIV infection was therefore investigated. The DAT results
      indicated that 96 of the patients had leishmanial infections, although
      amastigotes were only detected in samples from 91. Data on HIV status showed that
      50.7% of all patients but 56.0% of the parasitologically confirmed cases of VL
      patients were HIV-positive. Based on the 95 patients who were each examined both
      by DAT and parasitological methods, the overall sensitivity of the DAT was 97.7%.
      Among the parasitologically confirmed cases of VL, a false-negative DAT result
      was obtained for two (3.9%) of the 51 cases who had HIV co-infection and for none
      of the 40 HIV-negative cases. In contrast to the observations made in Europe, DAT
      in Ethiopia therefore remain reasonably sensitive in the diagnosis of VL during
      HIV co-infection. The results are discussed in view of the possibility of
      distinctive antibody responses induced by Leishmania donovani donovani and L. d.
      infantum in HIV-infected patients.

PMID- 11989531
TI  - DNA extraction and amplification of leishmania from archived, Giemsa-stained
      slides, for the diagnosis of cutaneous Leishmaniasis by PCR.
AB  - DNA was isolated from 92 Giemsa-stained smears of lesions from suspected cases of
      cutaneous leishmaniasis and used for PCR-based diagnosis of Leishmania infection.
      Each smear had been examined under a light microscope at x 1,000 and scored for
      amastigote numbers. Although the smears had been stored for up to 4 years, all
      the microscopy-positive slides were also positive by PCR and four of the 14
      smears that were negative by microscopy (although of lesions that were clinically
      consistent with leishmaniasis) were also PCR-positive. PCR-based investigations
      therefore appear to offer an effective method to confirm suspected cases of
      cutaneous leishmaniasis using (even archived) samples that have been collected,
      from humans (and reservoir hosts) in the field, by simple methods.

PMID- 11989532
TI  - Kinetics of the nucleoside triphosphate hydrolase of Toxoplasma gondii in mice
      with acute and chronic toxoplasmosis.
AB  - The kinetics of the nucleoside triphosphate hydrolase (NTPase) of Toxoplasma
      gondii was examined using an avidin-biotin sandwich-ELISA (ABS-ELISA) based on an
      anti-NTPase monoclonal antibody, 6C6. The RH and ME49 strains of the parasite
      were used to produce acute and chronic infections in mice, respectively. In the
      acute model, detectable serum concentrations of NTPase were observed from day 1
      post-infection and gradually increased until the death of the mice. They were
      associated with parasitaemia (as estimated by bioassay). No anti-T. gondii
      antibody could be detected at any time. In the chronic model, in which 20 T.
      gondii ME49 cysts were given to each mouse per os, the NTPase concentration
      generally increased from day 3, peaked between days 7 and 14 and then declined.
      However, one of the four mice used still had a high serum concentration of NTPase
      on day 35. Again, detectable NTPase concentrations occurred when the mice had
      parasitaemias. Antibody to T. gondii was detected from day 7 (IgM) or 10 (IgG)
      and brain cysts were observed from day 14. Since detectable serum concentrations
      of NTPase appear to be associated with parasitaemia in both acute and chronic
      toxoplasmosis, the ABS-ELISA of the enzyme may make a useful diagnostic tool.

PMID- 11989533
TI  - A case-control study of the risk factors for cystic echinococcosis among the
      children of Rio Negro province, Argentina.
AB  - In 1984 the prevalence of cystic echinococcosis (CE) in Rio Negro province in
      central Argentina reached alarming levels, with almost 6% of children aged 7-13
      years infected with the causative agent, Echinococcus granulosus. Although the
      control activities developed between 1980-2000 have now lowered the prevalence of
      infection in this age-group to 1.1%, transmission of E. granulosus has clearly
      not ceased. The aim of the present study was to identify possible flaws in the
      control programme and the risk factors associated with CE. The 24 cases and 66
      controls used were identified during a survey of the 1,070 schoolchildren
      attending 12 schools in Ingeniero Jacobacci, Rio Negro province. In interviews
      based around a standardized questionnaire, the adult female with responsibility
      for each subject (usually the mother but sometimes a grandmother or guardian) was
      asked 70 questions about the child and his or her immediate family, their contact
      with dogs and relevant environmentmental factors, and their level of contact with
      the control programme. Univariate and multivariate analyses were used to
      determine odds ratios (OR) and their 95% confidence intervals (CI). The main risk
      factors found to be significantly associated with CE were having a family member
      with the disease (OR = 3.11; CI = 0.92-10.47), spending the first years of life
      surrounded by a large number of dogs (OR = 2.11; CI = 1.2-3.5), and having a
      father who slaughtered sheep at his workplace (OR = 1.14; CI = 1.04-1.24).
      Obtaining drinking water from a tap (OR = 0.28; CI = 0.08-1.01) also remained in
      the final model, as a protective factor.

PMID- 11989534
TI  - Intestinal helminths and malnutrition are independently associated with
      protection from cerebral malaria in Thailand.
AB  - Although human infection with Ascaris appears to be associated with protection
      from cerebral malaria, there are many potential socio-economic and nutritional
      confounders related to helminth infection that need to be considered. In a
      hospital-based study, 37 cases of cerebral malaria and 61 cases of non-severe
      malaria with high parasite biomass (i.e. hyperparasitaemia and/or circulating
      schizonts) answered a structured questionnaire and were screened for intestinal
      helminths. Logistic regression was then used to adjust for the potential
      confounders. The adjusted odds ratios (OR) and their 95% confidence intervals
      (CI) still showed a significant protective association for helminths (OR = 0.24;
      CI = 0.07-0.78, P = 0.02) and malnutrition (OR = 0.11; CI = 0.02-0.58; P = 0.01),
      with no evidence of interaction between the two. There was also a significant
      dose-effect trend for the helminth infections (P = 0.048). These results, despite
      coming from a hospital-based study, indicate that the apparent association
      between helminths and protection from cerebral malaria is not the result of socio
      economic or nutritional confounders.

PMID- 11989535
TI  - Using ivermectin-treatment coverage among schoolchildren monitored by
      schoolteachers as a proxy of population coverage in areas of Uganda where
      onchocerciasis is endemic.
AB  - In the control of onchocerciasis using mass treatment with ivermectin, coverage
      needs to be monitored regularly so that communities with poor or insufficient
      coverage can be identified and timely and appropriate interventions then
      instituted. The aim of the present study was to assess whether ivermectin
      treatment coverage in schoolchildren, as monitored by schoolteachers, could be
      used as a proxy of population coverage. Although the coverages estimated in
      schoolchildren were found to be significantly correlated with estimates based on
      household surveys (P=0.01), there was poor correlation between either school and
      household-survey coverage and the values recorded in community registers.
      Although the community-register figures are the ones which the district health
      services normally use to report treatment coverage, they may be unreliable.
      Ivermectin-treatment coverage in schoolchildren monitored by schoolteachers could
      give a good and more accurate approximation of total population coverage.
      Further, large-scale studies, that take into consideration the cost-effectiveness
      of the various methods available to validate reported treatment coverage, are
      recommended.

PMID- 11989536
TI  - Dynamics of the malaria-vector populations in coastal Lagos, south-western
      Nigeria.
AB  - An entomological study was carried out in coastal Lagos, south-western Nigeria,
      to explore the role of Anopheles gambiae s.l. and An. moucheti in the
      transmission of Plasmodium falciparum in this holo-endemic area. Mosquitoes were
      caught, on human bait at night and by pyrethrum-spray catches during the day,
      twice a month throughout 2000. Of the 1812 Anopheles mosquitoes collected, An.
      gambiae s.l., the predominant vector species, represented 78.7% while the other
      21.3% were An. moucheti. The results of a PCR-based test identified 56.8% of the
      mosquitoes of the An. gambiae complex collected as An. gambiae s.s., 36.9% as An.
      melas and 6.3% as An. arabiensis. Anopheles gambiae s.s. was predominantly
      recorded in the wet season, biting females being collected from May to October,
      with a peak in July. Anopheles melas and An. moucheti were present throughout the
      year-long study whereas An. arabiensis was mainly found in the dry season. The
      results of ELISA-based analyses of bloodmeals indicated that An. gambiae s.s.,
      An. melas and An. moucheti were predominantly anthropophagic whereas An.
      arabiensis was largely zoophagic. Among all of the females investigated, 3.6% of
      the An. gambiae s.s., 1.9% of the An. melas, 1.8% of the An. moucheti and 0% of
      the An. arabiensis were found to be infected with P. falciparum (i.e. carrying
      the parasite's circumsporozoite antigen). The corresponding proportions for the
      females collected during the dry season were 1.3%, 2.3%, 2.7% and 0%. The
      entomological inoculation rates for An. melas and An. moucheti were significantly
      higher during the dry season than at other times of the year. Taken together,
      these results indicate that An. melas and An. moucheti maintain transmission of
      P. falciparum during the dry season, while the biting population ofAn. gambiae
      s.s. is relatively small.

PMID- 11989537
TI  - Distribution of putative male sex pheromones among Lutzomyia sandflies (Diptera:
      Psychodidae).
AB  - Male Lutzomyia longipalpis produce terpene sex pheromones in glandular tissue
      underlying the cuticle. The pheromones are transmitted to the surface via cuticle
      lined ducts (measuring 0.25 microm in diameter), each of which reaches the
      surface in the centre of a papule (measuring 3-3.5 microm in diameter). Similar
      papules, in a range of shapes but all characterized by the presence of a central
      pore and absence of macroserae, occur in some other species of sandfly. The aim
      of the present study was to determine the distribution of sex pheromones in
      sandflies of the genus Lutzomyia that do and do not have the papules. The results
      indicate that sex pheromones are not widely distributed amongst male Lutzomyia
      spp. Male members of the genus can be subdivided into three groups: those that
      produce terpenes and have cuticular papules; those that do not produce terpenes
      but still have the associated papules; and those that have neither terpenes nor
      papules. The papules seen in the species that do not synthesise sex pheromones
      are presumably vestigial, non-functional structures. Such species may have
      stopped producing pheromone as the result of changes in the way in which the
      females found and selected mates or changing feeding preferences. A similar event
      has occurred in the Lepidoptera, where vestigial pheromone-secreting structures
      remain in some species which no longer produce pheromone. Lutzomyia lenti
      collected in southern Brazil produced a novel diterpene whereas male L. lenti
      from north-eastern Brazil did not, supporting suggestions by others that L. lenti
      is, like L. longipalpis, a species complex.

PMID- 11989538
TI  - Factors influencing participation in national immunization days in Kumasi, Ghana.
AB  - A study of the factors influencing participation in national immunization days
      (NID) in Kumasi, Ghana was carried out between the April and June of 1999. Polio
      immunization coverage during NID was assessed among children aged < 5 years; >
      90% of these children had received polio vaccinations on both of the two previous
      NID. The mothers who participated most in the NID tended to be those who were
      better educated and Ghanaian. Mothers who were salaried workers participated
      fully in NID. Radio and television played a major role in public education about
      NID, whereas the attitude of health workers was a strong factor that prevented
      many mothers/caregivers from bringing their children to be immunized. The
      coverage of the Expanded Programme on Immunization (EPI) was assessed in children
      aged 12-23 months; nearly 70% of these children were fully immunized. BCG had the
      highest coverage (97.0%) and measles the lowest (79%). Again, full coverage of
      the children of mothers who had been educated beyond primary level was higher
      than that of the other children (75.9% v. 65.2%), and coverage of the children of
      Ghanaian women was higher than that of the others (70.8%. v. 50.0%). Although the
      mothers/caregivers raised concerns about the costs of the routine immunizations,
      these charges apparently did not prevent them from taking their children to be
      immunized. NID complement the routine EPI-associated work in Ghana, increasing
      overall polio-immunization coverage. The results of this study will be used to
      improve the overall performance of immunization programmes, especially in the
      Kumasi metropolis. Hopefully, sustained, increased polio-immunization coverage
      will contribute positively towards polio eradication in Ghana.

PMID- 11989539
TI  - A study on the efficacy and safety of losartan in elderly patients with mild to
      moderate essential hypertension.
AB  - Despite progress in the detection and treatment of hypertension the percentage of
      patients with controlled hypertension has failed to increase. The problem of poor
      blood pressure control is even more serious in elderly hypertensives than in the
      rest of the population. The antihypertensive drugs of the AIIRA (non-peptide
      angiotension II receptor antagonist) class are drugs whose use and experience are
      increasing and whose properties make them particularly useful in the elderly. We
      tried to assess the efficacy of treatment with losartan, the first AIIRA drug in
      a cohort of elderly patients with essential hypertension and to assess the
      percentage of patients achieving optimum BP control and to evaluate its safety,
      tolerability and metabolic effects. The intervention proved to be highly
      effective, achieving the anticipated blood pressure levels in the elderly in 77%
      of subjects after a 16-week follow-up, with very good tolerability. Renal
      function remained unchanged, as did the subjects' lipid profile.

PMID- 11989540
TI  - Wild garlic has a greater effect than regular garlic on blood pressure and blood
      chemistries of rats.
AB  - When groups of 10 Spontaneously Hypertensive Rats (SHR) were fed diets containing
      either 1% w/w regular garlic (Allium sativum) (AS) or 1% w/w wild garlic (Allium
      ursinum) (AU) for 45 days, the final mean systolic blood pressure (SBP) was
      reduced significantly compared to control (C) (C 189; AS 175; Au 173 mm Hg).
      Compared to C, body weight and circulating glucose and triglyceride levels were
      not significantly different; but circulating insulin was significantly higher (C
      23.6; AS 33.9; AU 29.5 uIU/dl), and total cholesterol was significantly lower (C
      133; AS 115; AU 117 mg/dl) in the two groups consuming AS or AU. HDL rose in the
      two garlic groups, but the differences from C were statistically significant only
      for the AU group. In a second study, the effects of a lower dose of dietary AS
      and AU (0.1% w/w) on SBP and various blood chemistries were compared head-to-head
      in 80 SHR-40 control and 40 test rats. Both AS and AU decreased SBP significantly
      compared to a control group of 10 SHR followed simultaneously. However, AU at
      this lower concentration produced a significantly greater SBP-lowering effect
      compared to the AS group. In addition, AU decreased total cholesterol
      significantly and tended to increase HDL compared to AS. Accordingly, the results
      suggest that AU has a greater therapeutic benefit compared to AS at a given
      concentration.

PMID- 11989541
TI  - Renal function in the oldest-old on an acute geriatric ward.
AB  - AIM: Evaluation of renal function and relation to risk factors for renal failure
      in very old patients admitted to an acute geriatric ward. METHODS: Retrospective
      chart review of patients aged 80 years and over, admitted to the acute geriatric
      ward from August 1998 till August 1999. Recorded data were: age, gender, previous
      medical history, primary diagnosis, medication use, weight, serum creatinine,
      BUN, sodium, potassium, cholesterol, urine and ultrasound of the kidney. The
      creatinine clearance was estimated by the Cockcroft-Gault formula, the glomerular
      filtration rate by the MDRD equation. RESULTS: 220 (60 males/160 females)
      patients were included. The mean serum creatinine on admisssion and discharge was
      1.17 +/- 0.45 mg/dL and 1.11 +/- 0.48 mg/dL respectively. The mean estimated
      creatinine clearance in the very old was 38.11 +/- 12.04 mL/min on admission and
      39.00 +/- 11.01 mL/min on discharge. Renal failure arbitrarily defined as an
      estimated creatinine clearance on admission of less than 30 mL/min was found in
      26.4% of the patients. Only a significant correlation between failure to thrive
      and renal failure was found (p < 0.0001). The correlation coefficient between the
      Cockcroft-Gault and the MDRD formula was r = 0.66 (p < 0.0001); between the
      Cockcroft-Gault and the reciprocal serum creatinine was r = 0.60 (p < 0.0001) and
      between the MDRD and the reciprocal serum creatinine was r = 0.87 (p < 0.0001).
      CONCLUSION: The weak correlation between the Cockcroft-Gault and other
      estimations of GFR in the acutely ill elderly, confirms the need to have a
      reliable estimation of glomerular filtration rate in the elderly. Renal failure
      defined as a Cockgroft-Gault <30 mL/min is found in 26.4% of the oldest-old
      admitted to an acute geriatric department. The elderly with renal failure is more
      often admitted for failure to thrive. No great differences were observed between
      renal function on admission and discharge.

PMID- 11989542
TI  - The mechanism of increased renal susceptibility to toxic substances in the
      elderly. Part I. The role of increased vasoconstriction.
AB  - The mechanisms of increased susceptibility to nephrotoxins in aging are complex
      and incompletely understood. It is very important to try to increase our
      knowledge of them because adults become increasingly vulnerable to nephrotoxic
      substances, as they grow older. In addition, the percentage of elderly people
      will increase markedly in the near future, at least in the developed countries.
      Drugs such as diuretics, laxatives, NSAIDs, aminoglycosides and other nephrotoxic
      antibiotics, and converting enzyme inhibitors are used a lot by aging people and
      can produce severe renal problems. Beside drugs, the clinical use of
      radiocontrast agents also rises in older patients. It seems that the main
      mechanism of the increased renal susceptibility to toxic substances in the
      elderly is a disbalance between vasoconstrictor and vasodilator factors (in favor
      of vasoconstrictor ones). Increased propensity to vasoconstriction (to Ang II, ET
      and PAF), as well as increased levels of oxidatively modified biomolecules in the
      elderly, may enhance susceptibility of old kidney to toxic substances. In
      addition, all mechanisms that influence both mesangial and fibroblast cell
      proliferation and over-production of extracellular matrix might also be involved
      in the processes that make the old kidney prone to drug-induced chronic toxic
      injury.

PMID- 11989544
TI  - Multi-organ renal failure in the elderly.
AB  - Periodically the question is posed "Why the persistently high mortality in acute
      renal failure?". By 1986, little progress seemed to have been made in improving
      outcome and it was stated that once oliguria was resistant to volume replacement
      and cardiac support, the patient had at best only a 50% chance of surviving.
      During the period 1960-1985, it can be shown that although outcome was not
      improving, older and sicker patients were being treated. Reviewing the literature
      of the past decade, the age and case mix of patients appears stable, but there is
      no suggestion of improvement in outcome. ARF with sepsis continues to have a
      mortality of 65 to 80%, and the outcome remains poor in elderly patients with
      failure of two or more organs. Progress has been slow in Intensive Care Units,
      and the past 20 years has seen little more than a move away from parenteral
      towards enteral feeding. Recent advances, however, in ventilatory techniques and
      the use of supra-physiological doses of glucocorticoids may lead to some
      improvement in outcome.

PMID- 11989545
TI  - Geriatric nephrology and urology literature.

PMID- 11989543
TI  - Androgen therapy for anemia in elderly uremic patients.
AB  - Androgens were the mainstay of treatment of renal anemia prior to the
      introduction of recombinant human erythropoietin. With the introduction of this
      recombinant hormone, the protocols of treatment of anemia were completely
      modified, and the use of androgens was relegated to the background. However,
      several authors have continued showing interest in the use of androgenic steroids
      for the treatment of anemia. This review examines several aspects of aging on
      androgenic hormones and hematopoiesis, the effects of androgen administration on
      hematological parameters, the side effects of these compounds and the future of
      this treatment for anemia in renal patients.

PMID- 11989546
TI  - Urinary excretion of N-acetyl-beta-D-glucosaminidase in newly diagnosed essential
      hypertensive patients and its changes with effective antihypertensive therapy.

PMID- 11989547
TI  - Bedside ultrasound: a useful tool for the on-call urologist?
AB  - OBJECTIVE: To assess the accuracy and benefit of urgent bedside ultrasound
      scanning in urological emergencies by urology trainees. METHODS: In this
      prospective study, 111 patients (86 acute flank pain, 15 renal failure, 10
      haematuria) referred as urological emergencies, were scanned for urinary tract
      abnormalities at the bedside, by a trainee urologist, over 18 months. The
      ultrasound findings were compared with the results of imaging performed by a
      consultant radiologist and its influence on clinical management analysed.
      RESULTS: Bedside ultrasound proved life saving in 5 patients (2 pyonephrosis, 2
      leaking aneurysms, one bilateral ureteric injury). It significantly influenced
      management in 11 patients, excluded obstruction in the presence of infection.in
      13 patients, helped in early diagnosis in 32 patients and ruled out gross
      urological pathology in 28 patients. It was misleading in 22 patients, mainly
      with ureteric colic (where the timing of the test can affect the findings),
      though the outcome was not adversely affected in any. Bedside ultrasound was
      reasonably accurate (sensitivity 81% and specificity 92%). CONCLUSIONS: Bedside
      ultrasound is a useful tool to help the decision-making in urological emergencies
      and reasonably accurate in hands of a trainee urologist. It is especially helpful
      for excluding obstruction in presence of infection or renal failure. However it
      has inherent limitations in assessing acute ureteric colic.

PMID- 11989548
TI  - Combined treatment of immobilization staghorn stones in 14-year old boy.
AB  - We report a combined urologic treatment of bilateral staghorn stones, developed
      in a boy after prolonged immobilization for limb fractures. He underwent
      percutaneous nephrostolithotomy (PCNL) on the left side, and after three months
      pyelolithotomy and nephrolithotomy for stasis in the right kidney, followed by
      ESWL for residual calculus in the left ureter. He becomes stone free, with
      apparently normal kidney function.

PMID- 11989549
TI  - The effects of the nitric oxide donor molsidomine prevent in warm ischemia
      reperfusion injury of the rat renal--a functional and histophatological study.
AB  - Aim of this experimental study is to verify the protective effect of molsidomine
      on the renal function and structural modifications in the ischemia-reperfusion
      rat kidney. Sixty-eight male Sprague-Dawley rats, which were right nephrectomized
      and occluded left renal artery for 60 minutes were used. Group I (n = 10) Sham
      Operated animals, which only underwent right nephrectomy. Group II (n = 20)
      Untreated ischemic rats, which underwent left renal ischemia by occlusion of the
      renal artery for 60 minutes before blood flow was restored. Group III (n = 18)
      Molsidomine treated ischemic rats, Group IV (n = 20) L-NAME (N(G)-nitro-L
      arginine methyl ester) treated ischemic rats. Serum creatinine and blood urea
      nitrogen (BUN) were measured daily and biopsies were obtained from the remaining
      left kidneys. At seventh day, 55% and 50% of the rats remained alive at the G-II
      and G-IV respectively. Molsidomine treated rats (G-III) were alive and healthy at
      day 7. The serum creatinine and BUN levels were significantly higher in G-II and
      G-IV when compared with the sham-operated group (G-I). G-III rats showed a rapid
      return to the normal serum creatinine and BUN values on postoperative days 1, 2,
      3 and 4. The obtained values in G-II were significantly lower in comparison to
      the values of G-II and G-IV. The most severe damage (grade 3 to 4) was determined
      in the kidneys of rats from GII or GIV. The degree of renal tubular damage in
      GIII was evaluated as grade 1 or 2 tubular damage according to Jablonkski's
      scale. Our findings suggested that the administration of molsidomine may vanquish
      the pernicious effects of warm ischemia on kidney structure and function.

PMID- 11989550
TI  - Primary echinococcal disease of the kidney: the case for a more conservative
      approach.
AB  - PURPOSE: To evaluate conservative management of renal echinococcosis in cases
      with normal renal function and active disease. PATIENTS AND METHODS: From a
      series of 12 consecutive patients with primary renal echinococcosis, nephrectomy
      was suggested to 4 patients because of kidney destruction. One patient who denied
      surgery and 5, in whom serological tests were positive, were given mebendazole
      for 30 days. 3 patients with no evidence of active disease were not given any
      medication. RESULTS: The patient who denied nephrectomy and 1 out of 5 with
      positive serological tests did not respond to mebendazole treatment. The latter
      underwent a cyst excision. Thus, 4 responders to mebendazole and 3 who were not
      given any medication, avoided surgery and continue to have negative serological
      tests for more than 3 years. CONCLUSION: Conservative management and long term
      follow up are proposed for the non-active or mebendazole-responsive patients. For
      the non-respondents or the cases with kidney destruction, surgery is the only
      hope for cure.

PMID- 11989551
TI  - Lipoprotein abnormalities in patients with secondary renal amyloidosis.
AB  - The prevalance of hyperlipidemia in chronic renal failure (CRF) patients is
      higher than in general population. Secondary amyloidosis is a common cause of CRF
      in Turkey. In this study, 25 patients with CRF due to secondary renal amyloidosis
      (amyloid-CRF), 15 patients with CRF without amyloidosis-CRF and 17 healthy
      controls were studied for serum lipid parameters. The mean serum lipoprotein (a)
      [LP(a)] level in the patients with amyloid-CRF was significantly higher than in
      the controls (p < 0.01). The mean serum apolipoprotein B (Apo B), apolipoprotein
      E (Apo E) and triglyceride levels in the patients with amyloid-CRF were very
      significantly higher than in the controls (p < 0.001). The mean serum total
      cholesterol, low-density lipoprotein (LDL) levels in the patients with amyloid
      CRF were higher than in the controls (p < 0.05). The mean serum apo AI levels in
      the patients with amyloid-CRF was very significantly lower than in the controls
      (p < 0.001). The mean serum high-density lipoprotein (HDL) in the patients with
      amyloid-CRF was lower than in the controls (p < 0.05). The mean serum Lp (a), Apo
      AI, Apo B and Apo E levels in the patients with amyloid-CRF were significantly
      higher than in the patients with CRF (p < 0.01). The mean serum total
      cholesterol, trigliserides, LDL and HDL levels in the patients with amyloid-CRF
      were higher than in the patients with CRF (p < 0.05). There was not any
      correlation with serum lipid parameters and serum albumin and urine protein
      levels (p > 0.05). Our study suggests that serum lipid parameters are abnormal
      and might be the risk factor of atherosclerotic vascular disease and contribute
      to renal disease progression in the patients with secondary renal amyloidosis and
      lipid abnormalities were different from CRF with various etiology, without
      amyloidosis.

PMID- 11989552
TI  - Evaluation of organ sparing operation results from planned indications in
      patients with kidney cancer.
AB  - An analysis in 53 patients with kidney cancer has been conducted, a group on
      which kidney sparing operations have been performed. 25 women and 28 men have
      been examined at the age of 53.7 in the postoperative period of 7 divided by 130
      months. The average observation time without any recurrences or metastases was
      48.8 months. 5.7% local and 1.9% remote decease related recurrences have been
      found. The stage of clinical progression and the degree of histological
      malignancy are factors determining the five-year survival being 98.0%, while
      without any recurrences or metastases being 88.4%.

PMID- 11989553
TI  - Follow-up of a case of retroperitoneal fibroses treated sequencially via right
      side autotransplant and left uterolysis with wrapper of posterior preperitoneal
      fat.
AB  - We present a case of retroperitoneal fibrosis treated with a renal
      autotransplantation in a patient inicially treated with endourologic measures and
      corticotherapy without success. The extense ureteral affectation was the
      indication to carry out an autotransplant. The follow-up is of nine years, with
      the function of the renal unity still preserved. We checked the literature for
      the therapeutic possibilities, medical as much as surgical, of the
      retroperitoneal fibrosis with special attention to the usage of the refractory
      IRF to other treatments.

PMID- 11989554
TI  - Cranial blind-ending branch of a bifid ureter.
AB  - A case of cranial blind-ending branch of bifid ureter is presented in a woman.
      There were no associated complications requiring surgery. The anomaly was best
      shown with intravenous urography.

PMID- 11989555
TI  - Large infectious bladder stone after long delay in removing ureteral stent.
AB  - We herein present a case of formation of a large infectious bladder calculous
      resulted from placement of a double pigtail catheter for an extensive period. The
      concomitant poor function of the corresponding renal unit made selection of
      nephroureterectomy unavoidable in the management of our patient.

PMID- 11989556
TI  - Modified insitu vaginal wall sling in stress incontinence.
AB  - To assess the efficacy of a modified technique in stress incontinence, that is
      vaginal wall sling reinforced with two layers of vaginal wall sutured inferiorly.
      27 patients with Type II incontinence, 4 with Type III and 14 with mixed type who
      completed two years follow up were included into the study. Cure, improvement and
      failure rates were 84.4%, 8.9% and 6.7% respectively. Temporary retention is
      observed in 30 of the patients, vaginal stenosis and pelvic pain in 1 and suture
      granuloma in 5 of the patients. Reinforced insitu vaginal wall sling which gives
      additional support to urethral hammock inferiorly offers a better solution to
      both types of stress incontinence.

PMID- 11989557
TI  - Clam ileocystoplasty in adult nocturnal enuresis.
AB  - OBJECTIVE: We investigated the effect of clam ileocystoplasty in patients with
      nocturnal enuresis with urodynamically proven detrusor instability which was
      recalcitrant to conservative therapy. MATERIAL AND METHODS: Twelve patients (10
      males, 2 females) with ages ranging between 22 and 44 years (mean 32) underwent
      clam ileocystoplasty. In addition to cystometry all patients underwent pressure
      flow evaluation. Patients with obstruction; poor contractility and poor
      compliance that was diagnosed by pressure flow studies were not operated.
      RESULTS: In a mean 38 months of follow-up all patients were cured symptomatically
      and urodynamically except one. In this patient, symptomatic improvement was
      observed despite the persistence of detrusor instability. No patient needed
      intermittent self catheterization. There were no postoperative complications
      except an incisional hernia diagnosed after two years postoperatively and
      corrected surgically. CONCLUSION: Clam procedure could be the best treatment for
      patients with life long nocturnal enuresis recalcitrant to conservative therapy
      with coexistence of proven detrusor instability.

PMID- 11989558
TI  - The first micturition times of the newborns whose mothers were treated with
      magnesium sulfate.
AB  - BACKGROUND: The aim of this study was to determine whether magnesium sulfate used
      for the treatment of severe pre-eclampsia or eclampsia had an effect on the first
      micturition time of the newborn. METHODS: The first group included 20 newborns
      all of whose mothers had severe pre-eclampsia or eclampsia, and all mothers had
      been treated with magnesium sulfate according to the Parkland Memorial Hospital
      eclampsia regimen. The second group included 20 newborns all of whose mothers
      were normal pregnants, and did not receive any drug that had an effect on the
      contractility of smooth muscles. The first micturition times of all newborns in
      two groups were determined following delivery and were compared statistically.
      RESULTS: All newborns urinated in the first 24 hours. There were no statistically
      significant differences in the micturition times between the two groups (p >
      0.05). There was no residual urine after the first micturition, and none of them
      had any urinary tract abnormality and neurological pathology. CONCLUSIONS: From
      the results, it was concluded that magnesium sulfate had no effect on the first
      micturition time of the newborns, when applied according to the Parkland Memorial
      Hospital eclampsia regimen in severe pre-eclamptic or eclamptic pregnants.

PMID- 11989559
TI  - Symptoms and urodynamics after unsuccessful transurethral prostatectomy.
AB  - The aim of this study is to make symptomatic and urodynamic evaluation of the
      patients after unsuccessful primary transurethral prostatectomy (TURP). Symptom
      score was not significantly different before and after TURP. Voiding symptoms
      were improved but storage symptoms were impaired as well as a quality of life.
      Free flow was fairly improved after prostatectomy as well as obstruction grade.
      Detrusor instability and residual obstruction were the most frequently recognized
      factors for voiding disturbances. Secondary TURP, or bladder neck incision are
      indicated in only 25% of patients so it should be performed more cautiously.

PMID- 11989560
TI  - Prognostic significance of changes in prostate-specific antigen in patients with
      metastasis prostate cancer after endocrine treatment.
AB  - Patients with metastatic prostate cancer respond to androgen withdrawal therapy,
      but progression to androgen independence is frequently observed. To clarify the
      predictor of response to endocrine therapy, the role of PSA changes and the
      prognosis of the patients were evaluated in 115 Japanese cases of prostate cancer
      with distant metastases treated with androgen withdrawal therapy. When patients
      were divided according to the pretreatment PSA value (high, > or = 500, median;
      500 > PSA > or = 100, low; 100 >), patients whose initial PSA levels were high
      had a worse cause-specific survival. PSA value at 3 or 6 months following
      endocrine treatment, PSA nadir, and percent decrease of PSA were associated with
      prolonged survival. Clinical relapse was observed in 68 patients. Patients with
      distant recurrence had shorter time to PSA elevation than those with local
      recurrence. In metastatic prostate cancer patients treated with androgen
      withdrawal, serial measurement of PSA could distinguish nonfavorable responders
      early in the course of treatment and assist in monitoring for disease
      progression.

PMID- 11989561
TI  - Delayed orchiectomy after chemotherapy in patients with advanced testicular
      cancer.
AB  - INTRODUCTION: The therapeutic procedures in the management of testicular cancer
      are determined by histological findings in the removed testis and by the extent
      of the disease at the time of diagnosis. However, all advanced tumors could be
      treated by primary chemotherapy regardless of the histological findings. The
      current imaging techniques (ultrasound of the testis, abdominal and chest CT
      examination) and laboratory tests (determination of serum tumor markers AFP and
      hCG) provide sufficient evidence for the presence of cancer. When the diagnosis
      of advanced tumor is evident, it is possible to start the treatment without
      orchiectomy. The aim of this study was to evaluate the advantages of neo-adjuvant
      chemotherapy with delayed orchiectomy in the management of advanced testicular
      cancer. MATERIAL AND METHODS: A total of 36 patients with advanced germ cell
      testicular cancer underwent primary PVB or BEP chemotherapy without previous
      orchiectomy. Mean age of patients was 32 years. Detailed medical, surgical and
      urological examination showed pulmonary metastases and/or extensive abdominal
      tumorous masses imitating acute abdominal crisis and impaired drainage of the
      kidney due to ureteral obstruction. Searching for the origin, testicular tumor
      was detected. Eleven patients had a bulky disease in the retroperitoneum (Stage
      IIC), two had enlarged retroperitoneal lymph nodes (Stage IIB), two had enlarged
      mediastinal lymph nodes (Stage III) and other 16 patients had also pulmonary
      metastases, and 5 pts had pulmonary metastases only. The patients were treated
      with cisplatin-containing combination chemotherapy. Following completion of
      chemotherapy, orchiectomy was performed alone or simultaneously with
      retroperitoneal lymph node dissection (RPLND) and/or lung metastasectomy in cases
      with persistent residual mass. Following orchiectomy the patients were regularly
      checked and in cases with viable malignant tumor found in the testis sequential
      chemotherapy was administered. Similarly when the relapse of the disease was
      detected, the patients were treated with sequential chemotherapy. RESULTS:
      Complete disappearance of metastases was observed in 12 patients following
      chemotherapy alone. The residual mass persisted in 24 patients (in 22 out of them
      in the retroperitoneum and in two patients also in the lungs) and was removed
      surgically. The viable tumor in the removed tissue was found in one patient.
      Delayed orchiectomy was performed simultaneously with surgical removal of
      residual mass in the retroperitoneum in 24 patients and as a separate procedure
      in 12 patients who have been considered to be complete responders following
      chemotherapy alone. Residual viable tumor in testicular specimen was found in
      three patients, necrotic or fibrotic tissue in 18, and mature teratoma in 15
      patients. Overall survival of the patients was 26/36 (72.7%) at mean of 56.9
      months (range 7-145 months, median 50 months) since the start of the treatment.
      CONCLUSIONS: In patients with advanced germ cell testicular cancer preference
      must be given to the early beginning of intensive chemotherapy without the need
      of tissue diagnosis of primary tumor that should be obtained by orchiectomy.
      Benefit of this therapeutic approach is the timely management of acute abdominal
      and/or pulmonary symptoms of life-threatening distant metastases.

PMID- 11989562
TI  - Epidemiology of testicular tumors in Slovakia (1993-1997): preliminary report.
AB  - Worldwide increase of the incidence of testicular tumors was also reflected in
      the increasing number of these malignancies in the Slovak Republic. Lack of the
      accurate information about the occurrence of testicular tumors in Slovakia has
      helped to create a new multicentric retrospective study based on occurrence,
      histology, risk factors, diagnosis and treatment of this malignancy in Slovakia.
      The analysed study group consists of 1010 patients with testicular cancer,
      diagnosed from the beginning of 1993 to the end of 1997. Identification and
      histological data about the patients were obtained from the heads of departments
      of urology in Slovakia. In this study considerable differences were found between
      information obtained from departments of urology and information published by the
      National Cancer Register of the Slovak Republic. Ascertained information is
      higher than the one published by the National Cancer Register from the last five
      officially concluded years.

PMID- 11989563
TI  - Adenomatoid tumors of testis and epididymis: a report of two cases.
AB  - Adenomatoid tumors are rare benign tumors of female and male genital tracts. In
      this paper, we reported an epididymal and a testicular adenomatoid tumor in two
      patients presented with enlarged intrascrotal mass.

PMID- 11989564
TI  - Ectopic adrenocortical nodules along the spermatic cord of children.
AB  - OBJECTIVE: Nodules of ectopic adrenal cortex are found incidentally during
      inguinal operations. These rests have some clinical significance as they may
      undergo marked hyperplasia in conditions associated with excessive ACTH
      production, and occasionally may give rise to neoplasms. In the present study, it
      is aimed to evaluate the ectopic remnants of adrenal tissue encountered during
      the inguinal operations in children. PATIENTS AND METHODS: Four hundred and fifty
      two inguinal operations were performed on 397 children (325 male/72 female; mean
      age 2.7 years), during a period of 36 months. Nodules resembling ectopic adrenal
      tissue from eleven patients (2.7%) were removed and the histopathological
      examination was performed using hematoxylin-eosin staining. RESULTS: Ectopic
      adrenal cortical tissues were found in eight male patients (2%), located within
      the distal end of the spermatic cord. Macroscopically, the nodules were round to
      oval in shape, 1 to 5 mm in diameter, and bright yellow to orange in colour.
      Microscopically, they had three layers of adrenal cortex surrounded by a fibrous
      capsule and none contained any medulla. Hyperplasia or neoplastic changes were
      not detected, and no fetal cortex was identified. CONCLUSIONS: It is important
      for surgeons to be conscious of the possibility that a nodule along the spermatic
      cord may be the ectopic adrenal cortical tissue. As they are associated with
      hyperplasia and neoplastic change, removal of ectopic adrenal cortical tissue is
      warranted whenever it is encountered, but a routine search for them is not
      mandatory.

PMID- 11989565
TI  - Malignant mesothelioma of tunica vaginalis testis associated with long-lasting
      hydrocele: could hydrocele be an etiological factor?
AB  - A case of malign mesothelioma of tunica vaginalis testis in a 67 year old man
      with a 30 year history of hydrocele was reported. The diagnosis was made with an
      excisional biopsy performed in scrotal exploration and revealed epithelial type
      mesothelioma. High orchiectomy with hemiscrotectomy was performed. The patient
      had a local recurrence at the end of two years. As there were no distant
      metastasis only local excision was performed. In his sixth month after the second
      surgery he is still tumor free. Related literature reviewed.

PMID- 11989566
TI  - Peyronie's disease: epidemiology and clinical presentation of 134 cases.
AB  - OBJECTIVE: To investigate epidemiological and clinical features of Peyronie's
      disease in an unselected group of patients not seen by a urologist before.
      PATIENTS AND METHODS: A series of 134 consecutive cases with Peyronie's disease
      was evaluated regarding to the age at diagnosis, the symptoms and signs of the
      disease, and the site and formation of the scar. The medical history which could
      be possibly related with the onset of the disease was investigated as well.
      RESULTS: The disease mainly affected middle-aged men. While all men had a
      palpable scar, only 51 (38%) had noticed the induration. Curvature (mean: 35
      degrees) appeared in 87 men (65%) and caused sexual dysfunction due to severe
      penile deformity in 16 men (11.9%). 53 patients (39.5%) referred painful
      erections. In 11 men (8.2%) the onset of the disease was noticed after auto
      injections of vaso-active drugs for the treatment of previous erectile
      dysfunction, while 18 (13.4%) had a history of penile trauma during sexual
      intercourse or manipulation. No specific relation with diabetes mellitus and
      Duputren's contracture was identified. Scars, like elongated indurations with
      vague bounds, were mainly formed (77.6%) in the dorsal midline. CONCLUSIONS: The
      mean age of patients at diagnosis, the site of penile scars, and the activities
      of the affected men could advocate the hypothesis that trauma is the main causal
      factor for Peyronie's disease. In 21.6% of the patients, the lesion occurred
      after a traumatic activity. Sexual dysfunction due to severe penile curvature
      affected a small proportion of the patients. Thus, due to the diminution of pain
      spontaneously or after treatment, the patients with Peyronie's disease may have a
      normal life with satisfactory sexual function. In some selected cases surgery
      offers an effective result.

PMID- 11989567
TI  - An experience of percutaneous embolization to post-traumatic arterial priapism in
      a child.
AB  - We report an experience of percutaneous transcatheter embolization to
      posttraumatic arterial priapism in a child. Priapism was successfully treated
      with this method. Angiography with subsequent selective embolization should be
      considered to be the treatment of choice for arterial priapism in children as
      well as in adults when less invasive treatments fail.

PMID- 11989568
TI  - Multicentral clinical evaluation of the aetiology of erectile dysfunction: a
      survey report.
AB  - Patients with erectile dysfunction, who admitted to 4 different urological
      centres in Turkey were evaluated in terms of aetiological factors to establish
      the aetiology of erectile dysfunction in our population and compare it with the
      data derived from Western communities. After the history, physical examination,
      psychological evaluation and laboratory testing, a clinical diagnosis was
      established as primarily psychogenic, organic, or mixed aetiology. Mean patient
      age was 43.5 years (range 17 to 69), and 9 of the patients were unmarried. Of the
      patients 53 had vascular risk factors, and 10 reported a history of alcohol
      abuse. Eleven patients were using drugs that might interfere with the disorder.
      In this multicentral study of 115 impotent men, an organic cause was found in
      43%, psychogenic in 47%, and mixed in 19%. Mean age of the overall patients was
      43.48. When the ages of the patients with organic erectile dysfunction and those
      with psychogenic erectile dysfunction were compared, it was clearly seen that
      those with organic erectile dysfunction were much older (52.73 versus 33.02).

PMID- 11989569
TI  - Evaluation of side effects of sildenafil in group of young healthy volunteers.
AB  - We evaluated the safety and side effects of sildenafil in a group of sexually
      active volunteers younger than 40 years under conditions without sexual
      stimulation. Single oral dose of 50 mg dildenafil (n = 20) or placebo (n = 20)
      was randomly administered to 40 sexually active volunteers with the mean age of
      26.80 +/- 5.29 in sildenafil group and 25.70 +/- 4.95 in placebo group. All the
      subjects were informed about the study, but not about the medicine. The following
      tests were performed immediately before and 90 minutes after the administration
      of the medicine: resting heart rate, blood pressure, electrocardiogram, visual
      acuity, color vision. The subjects were also asked to describe any discomfort or
      difference. Mann Whitney U test was used for statistical analyses. The only
      statistically significant difference was between heart rates before and after the
      administration of the sildenafil (p = 0.02). Color vision, visual acuity tests
      yielded no differences. The decrease in blood pressure was not significant. The
      most common side effects were flushing (75% and 0%), headache (50% and 5%),
      dyspepsia (15% and 5%), unintentional incomplete sexual arousal (15% and 0%) and
      palpitation (15% and 10%) in groups of sildenafil and placebo, respectively. The
      only serious side effect requiring medical treatment was arthralgia on the knee
      in one subject. Although these side effects can be acceptable, the likelihood of
      these side effects needs to be made clear to potential users of this medication.

PMID- 11989570
TI  - Morbidity of flank incision in 100 renal donors.
AB  - OBJECTIVE: The purpose of this study is to determine the morbidity of lumbotomy
      incision used in the last 100 living related donor nephrectomies retrospectively.
      METHODS: Since March 1991, 100 donor nephrectomies were made to living donors
      with lumbar incision. Incisions made in lateral decubitus position, subcostally
      or by an 11th or 12th rib resection. Left nephrectomy to 83, and right
      nephrectomy to 17 donors was performed. In 2 patients, there had been a
      peritoneal defect which was closed with primary sutures. In 19 patients 3 cm or
      shorter and in 5 patients longer than 3 cm of pleural entry had occurred. In all
      of the patients laceration was repaired without placement of a chest tube,
      however a chest tube had to be placed in 2 donors after obtaining a control chest
      x-ray postoperatively. RESULTS: All the patients mobilized and began to take
      orally in the first post-operative day. Wound infection, pneumonia and deep vein
      thrombosis had detected in none of the patients. The patients were discharged on
      the 4th and 5th postoperative day. During their control after 1 month from the
      operation it was found that all of them had returned to their daily life. In the
      postoperative period incisional hernia occurred in 7 patients which didn't need
      surgical repair and none of them complained of cosmetic problem. There was no any
      other late term complication was seen due to flank incision. CONCLUSION:
      Lumbotomy incision in donor nephrectomy, either a rib resection or supracostal
      approach, is reliable, provides excellent exposure for surgeon and has minimal
      morbidity.

PMID- 11989571
TI  - The effect of fluvastatin of hyperlipidemia in renal transplant recipients: a
      prospective, placebo-controlled study.
AB  - Posttransplant hyperlipidemia is a common complication which may affect long term
      cardiovascular mortality. In this prospective, placebo-controlled study, 19 renal
      transplant recipients (11 male 8 female, mean age 31.2 +/- 8.4 years) with good
      allograft function (serum creatinine <2 mg/dl) more than 6 months after
      transplantation were included. All the patients had hyperlipidemia (serum
      cholesterol >230 mg/dl and/or LDL-cholesterol >130 mg/dl) despite dietary
      interventions. The patients were treated with a triple immunosuppressive regimen.
      After a 8-week period of placebo plus diet regimen, the patients were put on
      fluvastatin plus diet for another 8 weeks. The patients were followed for its
      effect on lipid parameters and side effects. After convertion to fluvastatin,
      serum cholesterol (263.0 +/- 31.6 vs 223.2 +/- 31.6 mg/dl, p = 0.001), LDL
      cholesterol (174.4 +/- 28.3 vs 136.4 +/- 28.5 mg/dl, p = 0.002), Apolipoprotein
      (Apo) A1 (131.1 +/- 16.9 vs 114.7 +/- 18.4 mg/dl, p = 0.001) and Apo B (109.0 +/-
      29.8 vs 97.3 +/- 31.5 mg/dl, p = 0.02) levels decreased significantly. Serum
      levels of triglycerides, VLDL-cholesterol and HDL-cholesterol levels did not vary
      under fluvastatin. Serum lipoprotein (a) levels were also unchanged during the
      whole study period (24.9 +/- 19.4 vs 23.1 +/- 19.8 mg/dl, p > 0.05). We concluded
      that fluvastatin effectively decreased atherogenic lipoproteins such as serum
      cholesterol, LDL-cholesterol, Apo B in posttransplant hyperlipidemia, however
      fluvastatin had no effect on another independent risk factor of atherogenesis,
      serum lipoprotein (a) levels.

PMID- 11989572
TI  - Myocardial revascularization in patients with end-stage renal disease: comparison
      of percutaneous transluminal coronary angioplasty and coronary artery bypass
      grafting.
AB  - BACKGROUND: Ischemic heart disease is the major cause of death in patients with
      end-stage renal disease. The high prevalence of coronary artery disease results
      in a rising number of dialysis patients requiring myocardial revascularisation.
      OBJECTIVE: The objective of this study was to compare the outcomes of recurrent
      angina, myocardial infarction, rate of reinterventions and cardiovascular death
      following percutaneous coronary angioplasty (PTCA) or coronary artery bypass
      grafting (CABG) in patients with end-stage renal disease. PATIENTS AND METHODS:
      In a retrospective investigation 40 patients with chronic renal failure
      undergoing primarily PTCA and 65 patients undergoing CABG were included. Both
      groups were comparable for gender, duration on dialysis and the number of
      cardiovascular risk factors per patient. Patients undergoing PTCA were younger
      (53 +/- 12 years vs. 57 + 8 years; p < 0.05) and more often diabetics (30% vs.
      14%; p < 0.05). RESULTS: Most patients in both groups had a multi-vessel disease
      (95% in the CABG group vs. 74% in the PTCA group), in the CABG group there were
      significantly more patients with a triple-vessel disease (62% with vs. 40% in the
      PTCA group; p < 0.01), PTCA was primarily successful in 95% of the patients while
      complete revascularization was achieved in 88% of patients undergoing CABG. The
      perioperative mortality after CABG was 4.8% as compared to none after
      interventional revascularisation. The cumulative freedom of angina after 6, 12
      and 24 months after intervention was significantly lower after PTCA (54%, 40%,
      29%) than after bypass grafting (97%, 94%, 90%, p < 0.001). The frequency of
      reinterventions following PTCA was significantly higher compared to patients
      following CABG (p < 0.001). After PTCA 15 patients needed further
      revascularisations, 8 of them underwent CABG, whereas after CABG only two
      patients required additional myocardial revascularisation. There was no
      significant difference in the overall mortality between both groups; the survival
      rate after 12 and 24 months was 95% and 82% after PTCA and 93% and 86% after
      CABG, respectively. CONDITION: Although patients receiving CABG had a more severe
      coronary artery disease the overall mortality was comparable and clinical and
      functional outcome was improved compared to patients after coronary angioplasty.

PMID- 11989573
TI  - Rickettsioses: the new and old diseases.

PMID- 11989574
TI  - Endemic typhus in Singapore--a re-emerging infectious disease?
AB  - Singapore is a modern urban city and endemic typhus is thought to be a disease of
      the past. This may be due to lack of specific serological testing as indirect
      immunoperoxidase testing using specific rickettsial antigens (U.S. Army Medical
      Research Unit, Institute of Medical Research, Kuala Lumpur, Malaysia) has only
      recently become available. In the last fourteen months, twenty-one cases of
      endemic typhus were diagnosed in patients hospitalised for acute febrile
      illnesses at the National University Hospital. We conducted a case control study
      to define the clinical and laboratory features of endemic typhus in Singapore.
      METHOD: Demographic, clinical and laboratory data were reviewed for cases and
      twenty-one age and sex matched controls who had negative serologic tests as part
      of a work-up for fever of unknown origin. RESULTS: Apart from a higher initial
      temperature (39 degrees C vs 37.9 degrees C (p < 0.001)) and ALT(p = 0.002),
      cases and controls had similar presentations of fever, myalgia, headache, cough,
      normal WBC and platelet counts. Singapore residents and migrant workers were
      represented in both groups (p = ns). CONCLUSION: Endemic typhus remains an
      important cause of acute febrile illness in Singaporein both the local and
      migrant worker populations. The presentation is similar to other causes of acute
      febrile illnesses and the diagnosis will be missed unless it is specifically
      sought.

PMID- 11989575
TI  - Epidemiological, clinical and laboratory characteristics of 19 serologically
      confirmed rickettsial disease in Singapore.
AB  - AIM: To identify epidemiological, clinical and laboratory features of
      serologically-proven typhus in the local setting. METHOD & RESULTS: Retrospective
      study looking at rickettsial serologies done over a six-month period and
      collection of the epidemological, clinical, laboratory and treatment response
      data from the case notes of the patients with an ordered rickettsial serology.
      Twenty of the 35 cases had a positive serology. Of these 20 patients, 18 were
      already clinically diagnosed as having murine typhus. All except one were males
      and all were migrant workers. Majority of the patients were construction workers
      staying in containers where rats abound. The most consistent clinical features
      were high fever (100%) for a median period of seven days, headache (94%) and
      cough (47%). The white cell count was usually normal (74%) but thrombocytopenia
      was common (68%). Transaminitis was also common (90%) with the AST component
      higher than the ALT in half of the cases. Response to doxycycline therapy was
      rapid and most (88%) were afebrile by 72 hours. CONCLUSION: Typhus (notably
      murine type) can be confidently diagnosed from consistent clinical features
      supported by epidemiological and laboratory clues. Early recognition with the
      prompt treatment response will result in shorter hospital stay with decreased
      cost. Serological testing may only prove useful in difficult situations when the
      clinical diagnosis is less clear.

PMID- 11989576
TI  - The disability profile of patients with schizophrenia in psychiatric hospital and
      community settings in Singapore.
AB  - The disability profile of persons with schizophrenia in Singapore and how
      disability levels vary in patients cared for in the community and in the long
      stay wards of a state mental hospital were studied using the Life Skills Profile
      (LSP). The inter-rater reliability of the LSP assessed by the intraclass
      correlation coefficient (ICC), was lower than in the Australian studies. The test
      retest ICCs for the total LSP score and the five subscale scores were
      satisfactory for the hospitalised subjects and for the community psychiatric
      nurse subjects, but generally poor for the community care facility subjects. The
      average ICCs were lower compared to the Australian study. Female hospitalised
      subjects but not male hospitalised subjects returned higher disability scores on
      all LSP scales compared to community subjects. This study provided some
      preliminary data on the usefulness and validity of the LSP in a multi-ethnic
      Asian setting like Singapore. If the LSP is used as a measure of disability in
      schizophrenia, it would appear that ratings should only be made by those who know
      the subject well, and that raters should be formally trained mental health
      professionals.

PMID- 11989577
TI  - Clinical measurement of longitudinal femoral overgrowth following fracture in
      children.
AB  - We have studied residual limb length inequality following femoral shaft fractures
      in 62 children. From 61.2% of the children who had shortening of more than 1 cm
      at union, 34.21% still maintained the shortening at the completion of study. The
      longitudinal femoral overgrowth occurred significantly during the first 18 months
      of the fracture in 77.4% of the children, with an average of 1.17 cm. Children
      with proximal-third fractures and those who sustained the fractures before eight
      years of age have higher capability to correct the limb length disparity.

PMID- 11989578
TI  - A case series of drug-induced long QT syndrome and Torsade de Pointes.
AB  - INTRODUCTION: Torsade de Pointes (Tdp) is a form of polymorphic ventricular
      tachycardia in the setting of prolonged QT interval. Any drug that prolongs
      repolarisation, and hence QT interval, may cause Tdp. Predisposing factors of
      drug-induced Tdp include female sex, bradyarrhythmia and hypokalaemia. METHODS:
      We retrospectively analysed the case notes of 13 patients with drug-induced LQTS
      from 1991 to 2000 from National Heart Centre and Changi General Hospital.
      RESULTS: Causative drugs in the series were amiodarone (seven patients, 54%),
      sotalol (two patients), quinidine (one patient), phenothiazine (two patients) and
      astemizole (one patient). There were eight females and all were Chinese. The mean
      age was 72 +/- nine years. The patients commonly present with syncope (38%) and
      cardiac arrest (38%). The mean corrected QTC interval was 545 ms. The most common
      precipitating factor was hypokalaemia (31%). Nine patients require
      cardiopulmonary resuscitation and two patients (15%) died. Nine patients (69%)
      had underlying structural heart disease such as ischaemic heart disease, valvular
      heart disease and hypertensive heart disease. The left ventricular ejection
      fraction was normal in six patients. The onset of Tdp ranged from Day 2 to Day 5
      in the seven patient with amiodarone-induced LQTS. These were inpatients who were
      given intravenous loading doses of amiodarone. Both patients with sotalol-induced
      LQTS were females on sotalol 80 mg and 240 mg per day with Tdp occurring on Day 2
      and 10 months respectively. CONCLUSION: Tdp is a potentially life-threatening
      arrhythmia. The list of torsadogenic drugs is ever expanding. Physicians need to
      know the drugs which can lead to Tdp. Careful assessment of risk-benefit ratio is
      important before prescribing such drugs. Amiodarone-induced Tdp is not uncommon
      in our local population. Initiation of a class III agent, especially amiodarone,
      should be done judiciously, with monitoring of the QT interval and avoidance of
      hypokalaemia.

PMID- 11989579
TI  - New challenges facing the doctor-patient relationship in the next millennium.

PMID- 11989580
TI  - Professionalism in medical practice in reference to physician-to-physician
      relationship in the Singapore context.

PMID- 11989581
TI  - Doctor-patient relationship: a covenant of trust.
AB  - The goals of medicine as a profession dedicated to healing and caring of the sick
      in a dignified manner depend very much on a stable and trusting doctor-patient
      relationship. In the last decade, rapid changes in the healthcare delivery system
      and socio-political climate have resulted in considerable strain on this
      relationship. What is needed is a reiteration of the fiduciary obligation of the
      physician and the central role of the patient in the relationship. Concrete steps
      and changes at the institutional and individual levels need to be taken to
      preserve the element of trust in the patient-physician covenant. Only then can
      the medical profession retain the moral dimension of its role in society.

PMID- 11989582
TI  - Ethical sensitivity and the goals of medicine: resisting the tides of medical
      deprofessionalisation.
AB  - There is a growing concern that, like in many developed countries, medical
      practice in Singapore is fast losing its role and status as a profession. The
      commodification and industrialisation of health care, and weakening of its
      ethical foundations are among the main forces threatening to deprofessionalise
      the practice of medicine. To overcome these challenges, an honest and
      introspective review of the goals of medicine and an affirmation of the ethical
      values of medicine are needed in order to reinstate the unique role of medicine
      in our society. Important steps to take include adopting a patient-centred
      philosophy and practice culture, promoting and emphasising ethical awareness and
      sensitivity among physicians, and active participation in constructive dialogues
      to negotiate the social contract of the profession. A more permanent impact may
      be achieved through cultivation of medical virtues in physicians, and the
      integration of core elements of medical professionalism into the ethical systems
      and mission statement of today's health care organisations.

PMID- 11989583
TI  - Reconstructive challenges in the management of a rare case of sphenoid
      osteosarcoma--a case report.
AB  - Primary osteosarcoma of the sphenoid bone is an extremely rare condition. This
      paper presents a case of a lady with recurrent oesteosarcoma of the sphenoid bone
      who had resection of the tumour via a combined neurosurgical and craniofacial
      procedure and reconstruction with a free flap and bone graft. It details the
      diagnosis, treatment and follow-up of this unusual condition.

PMID- 11989584
TI  - Nocturnal enuresis and obstructive sleep apnoea in two children.
AB  - Nocturnal enuresis was a symptom of childhood obstructive sleep apnoea, OSAS. We
      reported two children with secondary nocturnal enuresis which disappeared after
      tonsillectomy and adenoidectomy for proven OSAS. Pathogenesis of secondary
      nocturnal enuresis in OSAS was discussed.

PMID- 11989585
TI  - Clinics in diagnostic imaging (68). Intradural extramedullary spinal
      paraganglioma.
AB  - Paragangliomas rarely present as spine tumours. The correct diagnosis is
      generally not suspected pre-operatively and initial imaging is often non
      specific. A 36-year-old man with low back pain, and progressive leg numbness and
      weakness, was found to have an expansile intradural extramedullary spinal tumour
      on radiographs and magnetic resonance imaging. Surgery revealed a paraganglioma.
      The features of spinal paraganglioma and differential diagnosis of intradural
      extramedullary tumours are discussed.

PMID- 11989587
TI  - Capecitabine: indications and future perspectives in the treatment of metastatic
      colorectal and breast cancer.
AB  - Fluoropyrimidines remain the most important drugs in the treatment of breast and
      colorectal carcinoma, but response rates and survival time have been
      disappointing. Optimal administration is by continuous intravenous infusion,
      which makes it cumbersome to use and compromises patient independence. Recently,
      a number of new agents, including fluorouracil prodrugs and selective
      dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising
      results. Capecitabine is the first in a new class of fluoropyrimidines. It is an
      oral, tumor-activated anticancer drug whose activity mimics that of continuously
      infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase
      catabolism and appears to be at least as active against metastatic colorectal and
      breast cancer as conventionally administered intravenous 5-fluorouracil, with
      significantly less toxicity, an improved quality of life, and lesser cost.
      Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil
      containing regimes for advanced colorectal and breast cancer.

PMID- 11989586
TI  - Biological predictors of response to radiotherapy in head and neck cancer: recent
      advances and emerging perspectives.
AB  - The study of new biological parameters has received considerable attention in
      radiotherapy during the last decade due to their potential value in predicting
      treatment response in squamous cell carcinoma of the head and neck (SCC-HN) and
      the foreseen possibility of selecting altered fractionation radiotherapy for the
      individual patient. Although there are established clinical parameters in SCC-HN
      patients that relate to radiation response (extent of disease, hemoglobin level),
      recent advances with direct measurement of tumor oxygenation, inherent
      radiosensitivity and proliferation rate have increased the promise of
      individualization of treatment strategy according to these radiobiologically
      based parameters. Molecular research has now identified a host of new biological
      parameters with potential predictive utility; oncogenes, tumor suppressor genes,
      cell-cycle control genes, apoptosis genes and angiogenesis genes have been
      extensively studied and correlated with radiation response. Moreover, study of
      the epidermal growth factor receptor signal-transduction system as a possible
      response modulator has recently fostered molecular strategies which employ
      blockade of the receptor to down-regulate tumor growth. This article briefly
      reviews and analyzes the main controversial issues and drawbacks that hinder the
      general use of biological parameters for predicting tumor response to
      radiotherapy. It highlights the future perspectives of radiotherapy predictive
      assay research and the need to shift from single-parameter analysis to
      multiparametric studies which take into account several potential predictors that
      together are involved in different biological and clinical pathways.

PMID- 11989588
TI  - Physical impairment and social life goals among adult long-term survivors of
      childhood cancer: a population-based study from the childhood cancer registry of
      Piedmont, Italy.
AB  - AIMS AND BACKGROUND: The study describes the health status and the attainment of
      life goals in the adult survivors of childhood cancer recorded at the Childhood
      Cancer Registry of Piedmont. METHODS AND STUDY DESIGN: A postal questionnaire was
      sent to the general practitioner of the 690 cases born before 1976 and alive in
      1991 after at least 5 years from diagnosis. The answer was received for 485
      (72.9%) included in the analyses. Items in the questionnaire were: sequelae
      related to cancer and its treatment, health-related quality of life (according to
      Bloom's criteria), educational level attained, and employment status. RESULTS:
      Vital and marital status were obtained for all 690 cases at the offices of the
      town of residence. No medical condition was reported for 309 cases (63.7%). The
      overall proportion with a high school or university education was compared to
      corresponding figures for Piedmont in 1991, adjusted by age, and was as high as
      in the general population. Similar results are observed for occupation. Patients
      of both genders were married less than expected. Patients with leukemia (112
      cases), non-Hodgkin's lymphoma (34) or Hodgkin's lymphoma (52) were reported to
      have the highest quality of life. In contrast, patients with tumors of the
      central nervous system (151) had the highest frequency of sequelae and the lowest
      score for health-related quality of life. They-also presented the lowest
      educational achievement, the lowest proportion of employment and, among males,
      the lowest frequency of marriage. CONCLUSIONS: Our study shows a good social
      adjustment of adult survivors from childhood cancer, with the exception of
      central nervous system tumors. From the methodologic point of view, the present
      study shows the feasibility of surveillance surveys on health-related quality of
      life with the contribution of general practitioners.

PMID- 11989589
TI  - Is an antiemetic prophylactic treatment needed for patients submitted to
      consecutive days of 5-fluorouracil? An observational study.
AB  - AIMS AND BACKGROUND: The necessity of an antiemetic prophylaxis in patients
      treated with chemotherapy of low emetogenic potential, such as 5-fluorouracil +/-
      folinic acid fractionated over several consecutive days, is controversial. The
      aim of the study was to evaluate the therapeutic behavior of oncologists on this
      issue. METHODS: All consecutive in and out patients who started chemotherapy in
      33 Italian oncological departments from June 24 to July 6,1996, were studied. The
      antiemetic prescription pattern and its effectiveness, in patients submitted to 5
      fluorouracil +/- folinic acid were evaluated. RESULTS: Of the 1956 patients
      submitted to cancer chemotherapy, 259 patients received 5-fluorouracil +/-
      folinic acid. Of these, 186 patients were treated for 5 consecutive days, 47 for
      4 days, 20 for 3 days and 6 for 2 days. A total of 219 (84.5%) received an
      antiemetic prophylaxis: 43.4% a 5-HT3 antagonist +/- steroids, 37.5% an
      antidopaminergic drug, 10.9% a steroid +/- antidopaminergic drug, and 8.2% other
      drugs. Only 40 patients (15.5%) did not receive an antiemetic prophylaxis.
      Overall complete protection from vomiting/nausea was 225/259 (86.9%)/163/259
      (62.9%). The complete protection from vomiting/nausea during the 5 days in the
      186 patients was not significantly different among patients receiving or not an
      antiemetic prophylaxis (88.1%/64.9% vs 88.9%/55.6%). At unifactorial analysis,
      the previous experience of vomiting/nausea caused by chemotherapy was found to be
      a significant prognostic factor. In fact, overall complete protection from
      vomiting/nausea was significantly inferior in patients who had previous
      experience of vomiting/nausea (65.1%/35.0%) with respect to those who did not
      (91.2%/75.4%, P < 0.001/ > 0.001, respectively). CONCLUSIONS: The study showed
      that in clinical practice patients submitted to 5-fluorouracil +/- folinic acid
      obtained a similar high protection from vomiting and nausea regardless of whether
      or not antiemetic prophylaxis was given. It would be therefore reasonable not to
      treat patients undergoing such chemotherapy, whereas patients with previous
      experience of vomiting/nausea caused by chemotherapy should be given an
      antiemetic prophylaxis.

PMID- 11989590
TI  - 5-fluorouracil-carboplatin continuous infusion as salvage chemotherapy in
      advanced cancer.
AB  - AIMS AND BACKGROUND: 5-fluorouracil given by continuous infusion allows higher
      dose delivery, causes less myelosuppression and may interfere with repair of DNA
      damage caused by carboplatin. With this rationale, we conducted a phase II study
      to test the activity and toxicity of 5-fluorouracil and carboplatin given in
      continuous infusion to patients with advanced cancer and pretreated with at least
      two chemotherapy regimens. METHODS: Forty patients with advanced tumors (21
      colon, 4 stomach, 3 breast, 3 bladder, 3 ovary, and 6 at other sites) were
      entered in the trial. 5-fluorouracil (200 mg/m2) and carboplatin (20 mg/m2) were
      administered by continuous infusion from days 1 to 20, every 4 weeks. RESULTS:
      All patients were assessable for response and toxicity. A total of 138 courses of
      chemotherapy were administered, with a mean of 3.5 per patient (range, 2-9).
      Toxicity, assessed using WHO criteria, was as follows: nausea and vomiting grade
      2-3 in 34% of patients, alopecia grade 2-3 in 96%, and neutropenia grade 3-4 in
      26%. One patient (2.5%) had a complete response to therapy and 7 (17.5%) had a
      partial response (response rate 20%; 95% Cl, 9.06-35.68%). Disease stability and
      progression occurred in 12 (30%) and 20 (50%) patients, respectively. Median time
      to progression was 5.6 months (range, 2.8-45.9+), with a median survival time of
      7.7 months (range, 1.5-45.9+). CONCLUSIONS: Outpatient treatment with a
      combination of 5-fluorouracil and carboplatin in continuous infusion was active
      as salvage treatment for advanced tumors and may give prolonged palliation of
      symptoms with manageable toxicity.

PMID- 11989591
TI  - Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from
      colorectal cancer: results of a phase I clinical study.
AB  - BACKGROUND: Hepatic arterial infusion chemotherapy is a promising approach in
      liver metastases from colorectal cancer, but chemical hepatitis, biliary
      sclerosis, arterial thrombosis and right upper quadrant pain are limiting
      factors. Irinotecan (CPT-11) is an active drug in colorectal cancer. We planned a
      short hepatic arterial infusion of CPT-11 to describe the toxicity, to determine
      the dose-limiting toxicity, and to define the doses of CPT-11 to be recommended
      for phase II studies. PATIENTS AND METHODS: Fourteen patients with a median liver
      substitution of 30% (10-60%) were enrolled. All patients received hepatic
      arterial infusion chemotherapy with CPT-11 on an outpatient basis every 3 weeks
      as a short, 30-min infusion. RESULTS: At 240 mg/m2, 2 of 4 patients experienced
      grade 4 diarrhea and neutropenia, and 3 of them also reported grade 4 abdominal
      pain of the right upper quadrant. The maximum tolerated dose was reached at 240
      mg/m2. The recommended doses of CPT-11 for phase II studies is 200 mg/m2, given
      every 3 weeks. CONCLUSIONS: CPT-11 presents a low hepatic toxic profile and could
      be considered a new active drug, suitable for hepatic arterial infusion in liver
      metastases from colorectal cancer.

PMID- 11989592
TI  - Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural
      mesothelioma: results of a pilot study.
AB  - AIMS AND BACKGROUND: The treatment of inoperable malignant pleural mesothelioma
      is a challenge for the oncologist. Available chemotherapy regimens achieve poor
      results, therefore new agents or combinations are needed. In a phase I study, the
      combination of oxaliplatin and raltitrexed was shown to be active against
      malignant pleural mesothelioma. We herein report the results of a pilot study
      about the treatment of this disease. METHODS: From April 1999 to June 2000, we
      enrolled 11 chemotherapy-naive patients with inoperable malignant pleural
      mesothelioma suitable to receive the following combination chemotherapy:
      raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3
      weeks. RESULTS: Four partial responses, 1 regression of disease (objective
      response rate, 45%; 95% CI, 15.6-74.4%), 4 stable diseases and 2 progressions of
      disease were observed. An improvement in disease-related symptoms was recorded in
      all responders and in 2 patients with stable disease. Toxicity was mild, with no
      toxic-related death and only 1 episode of grade 4 neurotoxicity. CONCLUSIONS: We
      consider the combination promising and worthy of further studies.

PMID- 11989593
TI  - Mitomycin C and vinblastine in anthracycline-resistant metastatic breast cancer:
      a phase II study.
AB  - The purpose of this phase II study was to evaluate the clinical efficacy of
      mitomycin C and vinblastine in patients with anthracycline-resistant metastatic
      breast cancer. This single-center, non-randomized trial enrolled 39 patients.
      Eligible patients must have received at least three chemotherapy regimens with
      epirubicin or CAF and had treatment failure while on chemotherapy or within 6
      months of completing therapy. Treatment consisted of mitomycin C at a starting
      dose of 8 mg/m2 on day 1 and vinblastine (8 mg/m2, days 1 and 28). The regimen
      was repeated every 6 weeks with a 20% dose escalation of both drugs after the
      first cycle in the absence of grade III hematologic or other toxicity. On an
      intent-to-treat basis, 38 patients were eligible for assessment; 9 (23.7%, 95%
      confidence interval 1.92-2.45%) achieved a partial response and 13 (34.2%) had
      stable disease. The median time to disease progression was 6.21+/-4.26 months
      (range, 1-15; 95% confidence interval, 4.81-7.61), and the median survival was
      10.76+/-7.6 (range, 1-29; 95% confidence interval 8.0-13.1%). Responsive patients
      had a significantly better survival than those with stable and progressive
      disease. Treatment was well tolerated. Anemia and neutropenia (grade I-III)
      developed in 28.9% and 26.3% of the patients, respectively. One patient with
      grade III granulocytopenia developed fever and infection that required
      hospitalization. Moderate neurotoxicity, myalgia, constipation, diarrhea and
      alopecia were observed. No toxic death occurred. Mitomycin C plus vinblastine is
      an effective and well-tolerated regimen for anthracycline resistant cancer.

PMID- 11989594
TI  - Concomitant radiotherapy with protracted 5-fluorouracil infusion in locally
      advanced carcinoma of the pancreas: a phase II study.
AB  - AIMS AND BACKGROUND: To evaluate the efficacy of combined radiation therapy and
      continuous infusion of 5-fluorouracil in patients with locally advanced carcinoma
      of the pancreas. METHODS: Between January 1992 and June 1999, 31 patients with
      locally advanced adenocarcinoma of the pancreas were treated in our Institute. In
      20 patients, the tumor (65%) was located in the head of the pancreas and in 11
      (35%) in the body or tail; 13 cases also showed involved nodes. Radiation therapy
      consisted in a median dose of 63 Gy in 33-36 fractions applied to the tumor and
      regional lymph nodes. Chemotherapy with 5-fluorouracil in continuous infusion,
      250 mg/m2 daily, was administered in the first and fifth week of the radiation
      therapy. Thereafter, 22 patients received 3-10 cycles of adjuvant chemotherapy
      with same doses. Median follow-up of the series was 20 months. The toxicity of
      the treatment was scored according to WHO criteria. All patients underwent
      nutritional assessment at the time of radiochemotherapy. RESULTS: The median
      overall survival was 15.2 months (range, 4-42). At restaging, 17 cases (55%)
      showed no change and 14 (45%) a partial remission. At the end of
      radiochemotherapy in 8 (26%) of the cases there was indication for
      pancreatectomy, which was executed in 4 patients. At the time of the study, 2
      patients (6.4%) were surgically proven disease free. Eleven of the 13 cases (85%)
      presenting involved nodes showed that the enlarged lymph nodes had disappeared.
      Nineteen patients (61%) are alive with clinical evidence of disease anti 2 cases
      are alive with liver metastases; 8 patients (26%) died for disease. In 74% of
      cases there was complete pain control. Tolerance to the regimen was good.
      Nutritional assistance was evaluated and was found to be correlated to survival.
      CONCLUSIONS: The results of the series confirm a good tolerance with low acute
      toxicity. Tumor down-staging and resectability rates were high, together with
      prolonged survival and a good quality of life.

PMID- 11989595
TI  - The role of total body irradiation in the conditioning of patients receiving
      haploidentical stem cell transplantation.
AB  - BACKGROUND: Nearly 40% of patients requiring a hematopoietic stem cell transplant
      lack a suitable donor. However, virtually all these patients have a potential
      family donor with whom they share one HLA haplotype. METHODS: We report the
      rationale for making hematopoietic stem cell transplantation from haploidentical
      related donors feasible, as well as the method followed to achieve this. Two
      studies are reported, designed to overcome the problem of rejection and graft
      versus-host disease after haploidentical stem cell transplantation. We describe
      how our total body irradiation-based, highly immuno- and myelosuppressive
      conditioning regimens were developed and how they have been modified over the
      years in an attempt to improve the clinical outcome of high-risk acute leukemia
      patients receiving large numbers of extensively T-cell-depleted hematopoietic
      stem cell transplantations from full-haplotype mismatched family donors. RESULTS:
      A high engraftment rate and an extremely low incidence of graft-versus-host
      disease were obtained. Modifications of the pretransplant schedules allowed the
      reduction of transplant-related toxicity. CONCLUSIONS: The main obstacles that
      limited the use of haploidentical stem cell transplantation have been overcome.
      The procedure is now a reality that should be recommended in high-risk acute
      leukemia patients who do not have a suitable matched donor.

PMID- 11989596
TI  - Bbr 2778, an aza-anthracenedione endowed with preclinical anticancer activity and
      lack of delayed cardiotoxicity.
AB  - With the aim to provide second-generation anthracenedione analogues endowed with
      reduced side effects and a wider spectrum of action than mitoxantrone and
      doxorubicin, a large number of new molecules bearing nitrogen atoms in the
      chromophore was synthesized and screened in vitro and in vivo. From this
      screening, BBR 2778 (6,9-bis[(2-aminoethyl)amino] benzo[g]isoquinoline-5,10-dione
      dimaleate) emerged as the most interesting compound. BBR 2778 was tested in vitro
      on several murine and human tumor cell lines and showed cytotoxic potency lower
      than that of mitoxantrone and doxorubicin. BBR 2778 was more cytotoxic in
      leukemia and lymphoma cell lines than in solid tumor cell lines. Although against
      in vivo models BBR 2778 was less potent than mitoxantrone and doxorubicin, its
      antitumor activity was equal or superior (in certain tumor models) to that of the
      above standard compounds. In particular, BBR 2778 was curative against L1210
      murine leukemia and YC-8 murine lymphoma. Moreover, it showed an antitumor
      activity comparable to that of mitoxantrone and doxorubicin on solid tumors. No
      cardiotoxic effect of BBR 2778 in animals not pretreated with anthracyclines was
      observed compared to standards. In light of its spectrum of activity and marked
      efficacy against lymphomas and leukemias over a wide dose range, together with
      its lack of delayed cardiotoxicity, BBR 2778 has been entered in clinical
      studies.

PMID- 11989597
TI  - Ginkgo biloba extract (EGb 761) modulates bleomycin-induced acute lung injury in
      rats.
AB  - The effect of Ginkgo biloba extract (EGb 761) on bleomycin (BLM)-induced acute
      lung injury was studied in rats. The responsiveness of isolated pulmonary
      arterial rings to 5-hydroxytryptamine (5-HT) as well as the levels of some
      relevant biochemical markers in the lung tissue were taken as evidence for the
      acute lung injury. BLM was given intraperitoneally at a dose of 15 mg/kg/day for
      five consecutive days. It was found that BLM treatment attenuated the
      vasoconstrictor effect of 5-HT on the isolated pulmonary arteries. In lung
      tissues BLM also elevated the level of lipid peroxides and enhanced the activity
      of glutathione peroxidase. On the other hand, the level of glutathione and the
      activity of alkaline phosphatase were reduced. Body weight, lung weight and
      tissue glutathione-S-transferase activity were, however, not altered. Oral
      administration of EGb 761 at a dose of 100 mg/kg/day for five consecutive days
      did not alter any of the chosen biochemical parameters in the lung tissue except
      for a slight reduction in alkaline phosphatase activity. However, treatment with
      EGb 761 reduced the responsiveness of the pulmonary artery to 5-HT.
      Administration of EGb 761 (100 mg/kg/day; po) two hours prior to BLM (15
      mg/kg/day; ip), for five consecutive days blunted the occurrence of further
      reduction in the vasoconstrictor response of the pulmonary artery to 5-HT.
      Furthermore, EGb 761 tended to normalize BLM-induced alterations in the measured
      biochemical markers in the lung tissue. The apparent modulatory influence of EGb
      761 on BLM-induced acute lung injury stems, at least in part, from its beneficial
      free radical scavenging properties that provide the extract with antioxidant
      activity.

PMID- 11989598
TI  - Tumor in tumor: metastasis of breast carcinoma to intracranial meningioma.
AB  - This report presents magnetic resonance imaging (MRI) findings of a breast
      carcinoma metastasis in an intracranial meningioma with correlated pathological
      findings. MRI showed multiple foci of intense enhancement with hypointense
      surrounding areas. The described foci appeared to be metastatic disease from the
      patient's known breast carcinoma. In addition, this is the first study reported
      in the literature to have investigated the expression of a possibly common
      carcinogenic molecule in breast carcinoma metastatic to a coexisting meningioma:
      overexpressed c-myc oncogene was found both in the breast carcinoma compartment
      and in the meningioma component of the tumor.

PMID- 11989599
TI  - Gemcitabine-induced radiation recall dermatitis: case report.
AB  - A 65-year-old male with lung adenocarcinoma received radiotherapy to the
      mediastinum and right upper lobe, followed by chemotherapy with gemcitabine.
      Radiation recall dermatitis developed in the area corresponding to the
      radiotherapy portal. This is one of just a few cases reported recently concerning
      radiation recall dermatitis stemming from gemcitabine.

PMID- 11989600
TI  - Sarcomatoid carcinoma of the colon: a case report with literature review.
AB  - Sarcomatoid carcinoma (SC) is a well defined tumor type that may occur in all
      organs and anatomic sites but most commonly in the head, neck, respiratory tract,
      breast, and genitourinary tract. It is a biphasic tumor showing both epithelial-
      and mesenchymal-like differentiation; however, its carcinomatous nature is widely
      recognized. SC is rare in the gastrointestinal tract. In the esophagus it
      accounts for less than 5% of all malignancies and approximately only 35 cases
      have been described in the stomach. Very few cases have been observed in the
      small intestine, anorectal junction, liver, and pancreas. To our knowledge only
      eight cases of SC have been reported in the colon. We report a case of primary
      colonic SC. Both morphological and immunohistochemical analyses are provided
      along with an evaluation of the unusual clinical history, therapeutic
      implications, and controversial differential diagnosis.

PMID- 11989601
TI  - Congenital infantile fibrosarcoma of the thigh in a newborn.
AB  - Congenital/infantile fibrosarcoma occurs frequently in the first year of life and
      differs from fibrosarcoma in adulthood. The clinical course of
      congenital/infantile fibrosarcoma is more favorable and metastatic spread is
      rare. While adult fibrosarcomas are common in the thigh, congenital/infantile
      fibrosarcomas affect chiefly the distal portions of the extremities. Standard
      treatment is primarily wide surgical excision. Chemotherapy may be given as
      neoadjuvant or adjuvant treatment in order to avoid the morbidity associated with
      wide excision. In this case report we present our experience of a newborn
      affected by congenital/infantile fibrosarcoma of the left thigh.

PMID- 11989602
TI  - Metastatic angiosarcoma of the spleen. A case report and treatment approach.
AB  - We report a case of a 28-year-old man with angiosarcoma of the spleen and liver
      metastases. The aim of this paper is to underline the importance of planned
      splenectomy in these patients even if they have metastatic disease, and to
      propose an intensive chemotherapy regimen consisting of anthracyclines,
      ifosfamide and mesna with G-CSF support.

PMID- 11989603
TI  - Primary intraosseous verrucous carcinoma developing from a maxillary odontogenic
      cyst: case report.
AB  - Primary intraosseous carcinoma (PIOC) is an extremely rare lesion, almost always
      occurring in cranial bones. The origin of this tumor, specific to the maxillae,
      is associated with the cells of the epithelial rests of Malassez. Among the
      histotypes which can be included in these neoplasms, verrucous carcinoma is of
      particular interest due to its rarity: only a single case has been reported to
      date. After a short survey of the literature, the authors describe a directly
      observed case of verrucous carcinoma arising from a maxillary odontogenic cyst.

PMID- 11989604
TI  - Occult small cell lung cancer associated with paraneoplastic neurologic syndrome:
      case report.
AB  - Cancer is often associated with paraneoplastic syndromes, which may be
      misinterpreted. We report a case of a patient with occult small cell lung cancer
      that was initially compounded by clinical features of a paraneoplastic neurologic
      syndrome. The presence of antineuronal antibodies and positron emission
      tomography scan guided the search for the underlying tumor. Following chemo
      radiotherapy the patient showed no evidence of disease for the next 18 months,
      whereas only a slight improvement in the neurologic disorders was observed. The
      course of the small cell lung cancer was very indolent and the paraneoplastic
      neurologic syndrome did not worsen with the use of cisplatin.

PMID- 11989605
TI  - Pituitary metastasis mimicking a macroadenoma from carcinoma of the larynx: a
      case report.
AB  - Metastatic tumors of the pituitary gland are not commonly diagnosed during life
      in cancer patients. The occurrence of symptomatic lesions is also very unusual
      and difficult to differentiate clinically and radiologically from pituitary
      adenomas. Furthermore, a single intrasellar metastasis from laryngeal carcinoma
      mimicking a pituitary adenoma is an extremely rare pathological finding. We
      report on the clinical, radiological, and pathological findings in a patient with
      laryngeal carcinoma who had a symptomatic solitary pituitary gland metastasis
      that was recognized antemortem.

PMID- 11989606
TI  - Breast carcinoma metastatic to the ethmoid sinus: a case report.
AB  - We report a rare case of breast carcinoma metastatic to the ethmoid sinus. An 83
      year-old female patient with an intraductal breast carcinoma presented the first
      symptoms of metastasis to the paranasal sinuses four years after radical
      mastectomy and axillary node dissection. A review of the literature revealed that
      only three such cases have been described so far. Symptoms and imaging results
      are not specific and usually similar to those of primary neoplasms in this
      region. This case underlines the importance of suspecting a metastasis in
      patients with a history of malignancy.

PMID- 11989607
TI  - Vaccination with T cell-defined antigens: biological basis and clinical
      applications.

PMID- 11989608
TI  - STI571 (glivec-tm): a new paradigm for the development of innovative therapies in
      onco-hematology?

PMID- 11989609
TI  - Inhibitors of histone-deacetylases.

PMID- 11989610
TI  - Anticancer therapy with angiogenesis inhibitors.

PMID- 11989611
TI  - Rationale, problems and perspectives in anti-angiogenic therapy.

PMID- 11989612
TI  - Membrane phosphoinositides as molecular targets for the control of motility and
      invasion of tumor cells.

PMID- 11989613
TI  - Signaling proteins as innovative targets for antineoplastic therapy: our
      experience with the signaling protein c-myc.

PMID- 11989614
TI  - Molecular prognostic indicators for breast cancer.

PMID- 11989615
TI  - Environmental carcinogenesis: tumor development and chemoprevention.

PMID- 11989616
TI  - Trop molecules as targets for anti-tumor immunotherapy in man.

PMID- 11989617
TI  - Use of human recombinant antibodies to the marker of angiogenesis ed-b in cancer
      therapy.

PMID- 11989618
TI  - Usefulness of endoscopic ultrasonographic analysis of variceal hemodynamics for
      the treatment of esophageal varices.
AB  - The correlation of between the endoscopic findings of esophageal varices and
      endoscopic ultrasound findings of the collaterals outside the esophageal wall in
      patients with portal hypertension remains unclear. We investigated the
      relationship between esophageal varices and the collaterals by endoscopy and
      endoscopic ultrasound. Moreover, we investigated the correlation between the
      collaterals around the esophagus and recurrence of esophageal varices in patients
      with portal hypertension who had undergone endoscopic injection sclerotherapy.
      The collaterals were divided into two groups: 1; those with peri-esophageal
      collateral veins (peri-ECVs) adjacent to the muscularis externa of the esophagus,
      and 2; those with para-esophageal collateral veins (para-ECVs) distal to the
      esophageal wall without contact with the muscularis externa. Peri- and para-ECVs
      were scored as mild or severe according to the stage of development. According to
      endoscopy, the varix form was significantly larger in severe peri-ECVs group than
      in mild peri-ECVs group. In contrast, the varix form did not differ significantly
      between the mild and severe para-ECVs group. The prevalence of perforating veins
      increased according to the varix form. With regard to variceal recurrence, in
      patients with variceal recurrences, EUS findings included a significantly higher
      incidence of severe-type peri-ECVs, a significantly larger number of perforating
      veins, and a significantly larger diameter of perforating veins compared with
      patients without recurrence. Moreover, when EUS found the abnormalities when no
      endoscopic recurrence was found, the results were the almost same as the findings
      when EUS was performed at the same time when endoscopic recurrence was found. In
      conclusion, the presence of severe peri-ECVs and large perforating veins in the
      esophageal wall strongly correlates with occurrence and recurrence of esophageal
      varices in patients with portal hypertension. An understanding of these EUS
      abnormalities on the basis of hemodynamics around the esophagus is thought to be
      important for management of esophageal varices in patients with portal
      hypertension.

PMID- 11989619
TI  - Biphasic cytokine expression by T cell clones from patients with atopic
      dermatitis with different incubation periods and strengths of stimuli.
AB  - It has been proposed that T helper (Th) 2 cells play a key role in the
      pathogenesis of atopic dermatitis (AD) because of clinical and experimental
      findings including hyper IgE, eosinophilia and Th2 type cytokine overexpression,
      etc. In contrast, several observations such as Th1 type cytokine detection in
      chronic lesions and histological features resembling allergic contact dermatitis
      suggest that Th1 rather than Th2 cells are important for the pathogenesis of skin
      lesions. In order to clarify this paradox, we investigated the function of T cell
      clones established from AD patients. Most T cell clones induced by house dust
      mite antigen and interleukin (IL)-2 from peripheral blood mononuclear cells of
      two AD patients exhibited CD4+/ CD8-, CD45RO+/ CD45RA-, and produced high levels
      of IL-4 and low levels of interferon-gamma (IFN-gamma) after phytohemagglutinin
      (PHA) (1 microg/ml) stimulation, suggesting a Th2 subtype. When stimulated with a
      high dose of concanavalin A (conA) (10 microg/ml), however, these clones produced
      high amounts of IFN-gamma. IL-4 production reached a peak 24 hours after conA (10
      ,g/ml) stimulation, whereas IFN-gamma production was increased up to 48 hours
      after stimulation. The findings of T cell receptor (TCR) stimulation with
      immobilized anti-CD3 monoclonal antibody (mAb) showed that the suitable strength
      of TCR stimulation for IFN-y production was higher than for IL-4. Also, in the
      TCR stimulated condition, the peak of IFN-gamma production was later than that of
      IL-4. These results indicate that T cell clones which exhibited a Th2 profile
      under weak stimulation can produce IFN-y in the late phase of stimulation when
      strong stimuli are used. The results are consistent with the previous observation
      that IFN-gamma production prominently appears in the chronic and late phase
      lesions of AD.

PMID- 11989620
TI  - Qualitatively different response of isolated rabbit aorta to methylene blue
      administered from intimal and adventitial surface.
AB  - An isolated rabbit aortic preparation, on which administered drugs act
      selectively from intimal or adventitial surface, was made. Epinephrine (0.1 nM
      approximately 10 microM) produced concentration-dependent increase of
      intraluminal pressure, which is due to increase of contraction of the vascular
      smooth muscle. Sensitivity of contractile response to epinephrine administered
      from intimal surface was significantly higher than that administered from
      adventitial surface. The contractile response to epinephrine administered from
      intimal surface was reduced by removal of the endothelium. Cocaine (100 microM)
      potentiated the contractile response to epinephrine administered from adventitial
      surface. Cocaine also potentiated the contractile response to high concentration
      of epinephrine administered from intimal surface, while the drug reduced the
      contractile response to low concentration of epinephrine. Methylene blue (100
      microM) administered from adventitial surface produced a marked contraction,
      while methylene blue administered from intimal surface produced a marked
      relaxation. The relaxing response to methylene blue administered from intimal
      surface was reduced by the removal of endothelium. Prazosin (1 microM) suppressed
      the contractile response to methylene blue administered from adventitial surface,
      indicating that methylene blue released norepinephrine from adrenergic nerve
      terminals. The contractile response to epinephrine administered from intimal
      surface was reduced by methylene blue administered from intimal surface. The
      present study clearly demonstrated variation in mechanical response of isolated
      rabbit aortic preparation with intimal or adventitial surface of drug entry.

PMID- 11989621
TI  - Antidromic effect of calcitonin gene-related peptide containing nerves on
      cerebral arteries in rats--a possible role of sensory nerves on cerebral
      circulatio.
AB  - It has generally been thought that the neurogenic control of cerebral circulation
      is decided mainly by the autonomic nervous system. Recent studies, however,
      indicate that sensory nerves rich in calcitonin gene-related peptide (CGRP) are
      also distributed on cerebral arteries. CGRP is one of neuropeptides that has
      strong vasodilative effect. This indicates that sensory nerves may antidromically
      dilate cerebral arteries mediated by CGRP. The aim of this study is to
      investigate the relationship between the CGRP containing nerves and cerebral
      circulation. Firstly, we developed a selective denervation model of CGRP
      containing nerves. The denervation was performed with intrathecal administration
      of capsaicin in rats. Secondly, we measured the change of regional cerebral blood
      flow (rCBF) during the occlusion of bilateral common carotid artery or systemic
      hypotension. CGRP immunoreactivity around cerebral arteries disappeared after
      capsaicin treatment. The rCBF during the occlusion of bilateral common carotid
      artery decreased more in the capsaicin group than in the control group. There was
      no significant difference in the changes of rCBF during systemic hypotension.
      These results showed that CGRP containing nerves would participate in the
      vascular response of cerebral arteries. It is likely that sensory nerves with
      CGRP should have antidromic effect on cerebral circulation.

PMID- 11989622
TI  - Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated
      buspirone analogues.
AB  - In the present study experimentally determined ligand selectivity of three
      methylated buspirone analogues (denoted as MM2, MM5 and P55) towards 5-HT1A and 5
      HT2A serotonin receptors was theoretically investigated on a molecular level. The
      relationships between the ligand structure and 5-HT1A and 5-HT2A receptor
      affinities were studied and the results were found to be in agreement with the
      available site-directed mutagenesis and binding affinity data. Molecular dynamics
      (MD) simulations of ligand-receptor complexes were performed for each
      investigated analogue, docked twice into the central cavity of 5-HT1A/5-HT2A,
      each time in a different orientation. Present results were compared with our
      previous theoretical results, obtained for buspirone and its non-methylated
      analogues. It was found that due to the presence of the methyl group in the
      piperazine ring the ligand position alters and the structure of the ligand
      receptor complex is modified. Further, the positions of derivatives with
      pyrimidinyl aromatic moiety and quinolinyl moiety are significantly different at
      the 5-HT2A receptor. Thus, methylation of such derivatives alters the 3D
      structures of ligand-receptor complexes in different ways. The ligand-induced
      changes of the receptor structures were also analysed. The obtained results
      suggest, that helical domains of both receptors have different dynamical
      behaviour. Moreover, both location and topography of putative binding sites for
      buspirone analogues are different at 5-HT1A and 5-HT2A receptors.

PMID- 11989623
TI  - Computational model of the complex between GR113808 and the 5-HT4 receptor guided
      by site-directed mutagenesis and the crystal structure of rhodopsin.
AB  - A computational model of the transmembrane domain of the human 5-HT4
      receptorcomplexed with the GR113808 antagonist was constructed from the crystal
      structure of rhodopsin and the putative residues of the ligand-binding site,
      experimentally determined by site-directed mutagenesis. The recognition mode of
      GR113808 consist of: (i) the ionic interaction between the protonated amine and
      Asp3.32; (ii) the hydrogen bond between the carbonylic oxygen and Ser5.43; (iii)
      the hydrogen bond between the ether oxygen and Asn6.55; (iv) the hydrogen bond
      between the C-H groups adjacent to the protonated piperidine nitrogen and the pi
      electrons of Phe6.51; and (v) the pi-sigma aromatic-aromatic interaction between
      the indole ring and Phe6.52. This computational model offers structural
      indications about the role of Asp3.32, Ser5.43, Phe6.51, Phe6.52, and Asn6.55 in
      the experimental binding affinities. Asp3.32Asn mutation does not affect the
      binding of GR113808 because the loss of binding affinity from an ion pair to a
      charged hydrogen bond is compensated by the larger energetical penalty of Asp to
      disrupt its side chain environment in the ligand-free form, and the larger
      interaction between Phe6.51 and the piperidine ring of the ligand in the mutant
      receptor. In the Phe6.52Val mutant the indole ring of the ligand replaces the
      interaction with Phe6.52 by a similarly intense interaction with Tyr5.38, with no
      significant effect in the binding of GR113808. The mutation of Asn6.55 to Leu
      replaces the hydrogen bond of the ether oxygen of the ligand from Asn6.55 to
      Cys5.42, with a decrease of binding affinity that approximately equals the free
      energy difference between the SH...O and NH...O hydrogen bonds. Because these
      residues are also present in the other members of the neurotransmitter family of
      G protein-coupled receptors, these findings will also serve for our understanding
      of the binding of related ligands to their cognate receptors.

PMID- 11989624
TI  - One site fits both: a model for the ternary complex of folate + NADPH in R67
      dihydrofolate reductase, a D2 symmetric enzyme.
AB  - R67 dihydrofolate reductase (DHFR) is a novel enzyme that confers resistance to
      the antibiotic trimethoprim. The crystal structure of R67 DHFR displays a
      toroidal structure with a central active-site pore. This homotetrameric protein
      exhibits 222 symmetry, with only a few residues from each chain contributing to
      the active site, so related sites must be used to bind both substrate
      (dihydrofolate) and cofactor (NADPH) in the productive R67
      DHFR.NADPH.dihydrofolate complex. Whereas the site of folate binding has been
      partially resolved crystallographically, an interesting question remains: how can
      the highly symmetrical active site also bind and orient NADPH for catalysis? To
      model this ternary complex, we employed DOCK and SLIDE, two methods for docking
      flexible ligands into proteins using quite different algorithms. The bound
      pteridine ring of folate (Fol I) from the crystal structure of R67 DHFR was used
      as the basis for docking the nicotinamide-ribose-Pi (NMN) moiety of NADPH. NMN
      was positioned by both DOCK and SLIDE on the opposite side of the pore from Fol
      I, where it interacts with Fol I at the pore's center. Numerous residues serve
      dual roles in binding. For example, Gln 67 from both the B and D subunits has
      several contacts with the pteridine ring, while the same residue from the A and C
      subunits has several contacts with the nicotinamide ring. The residues involved
      in dual roles are generally amphipathic, allowing them to make both hydrophobic
      and hydrophilic contacts with the ligands. The result is a 'hot spot' binding
      surface allowing the same residues to co-optimize the binding of two ligands, and
      orient them for catalysis.

PMID- 11989625
TI  - Molecular electrostatic potentials as input for the alignment of HIV-1 integrase
      inhibitors in 3D QSAR.
AB  - Comparative molecular similarity indices analysis (CoMSIA), a three-dimensional
      quantitative structure activity relationship (3D QSAR) paradigm, was used to
      examine the correlations between the calculated physicochemical properties and
      the in vitro activities (3'-processing and 3'-strand transfer inhibition) of a
      series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors. The
      training set consisted of 34 molecules from five structurally diverse classes:
      salicylpyrazolinones, dioxepinones, coumarins, quinones, and benzoic hydrazides.
      The data set was aligned using extrema of molecular electrostatic potentials
      (MEPs). The predictive ability of the resultant model was evaluated using a test
      set comprised of 7 molecules belonging to a different structural class of
      thiazepinediones. A CoMSIA model using an MEP-based alignment showed considerable
      internal as well external predictive ability (r2(cv) = 0.821, r2(pred) = 0.608
      for 3'-processing; and r2(cv) = 0.759, r2(pred.) = 0.660 for 3'-strand transfer).

PMID- 11989626
TI  - Structure-based ligand design for flexible proteins: application of new F
      DycoBlock.
AB  - A method of structure-based ligand design - DycoBlock - has been proposed and
      tested by Liu et al. It was further improved by Zhu et al. and applied to design
      new selective inhibitors of cyclooxygenase 2. In the current work, we present a
      new methodology - F-DycoBlock that allows for the incorporation of receptor
      flexibility. During the designing procedure, both the receptor and molecular
      building blocks are subjected to the multiple-copy stochastic molecular dynamics
      (MCSMD) simulation, while the protein moves in the mean field of all copies. It
      is tested for two enzymes studied previously - cyclooxygenase 2 (COX-2) and human
      immunodeficiency type 1 (HIV-1) protease. To identify the applicability of F
      DycoBlock, the binding protein structure was used as starting point to explore
      the conformational space around the bound state. This method can be easily
      extended to accommodate the flexibility in different degree. Four types of
      treatment of the receptor flexibility - all-atom restrained, backbone restrained,
      intramolecular hydrogen-bond restrained and active-site flexible - were tested
      with or without the grid approximation. Two inhibitors, SC-558 for COX-2 and
      L700417 for HIV-1 protease, are used in this testing study for comparison with
      previous results. The accuracy of recovery, binding energy, solvent accessible
      surface area (SASA) and positional root-mean-square (RMS) deviation are used as
      criteria. The results indicate that F-DycoBlock is a robust methodology for
      flexible drug design. It is particularly notable that the protein flexibility has
      been perfectly associated with each stage of drug design - search for the binding
      sites, dynamic assembly and optimization of candidate compounds. When all protein
      atoms were restrained, F-DycoBlock yielded higher accuracy of recovery than
      DycoBlock (100%). If backbone atoms were restrained, the same ratio of accuracy
      was achieved. Moreover, with the intramolecular hydrogen bonds restrained,
      reasonable conformational changes were observed for HIV- 1 protease during the
      long-time MCSMD simulation and L700417 was reassembled at the active site. It
      makes it possible to study the receptor motion in the binding process.

PMID- 11989627
TI  - Conformational analysis of nevirapine, a non-nucleoside HIV-1 reverse
      transcriptase inhibitor, based on quantum mechanical calculations.
AB  - The structure and the conformational behavior of the HIV-1 reverse transcriptase
      inhibitor, 11-cyclopropyl-5,11dihydro-4-methyl-6H-dipyrido[3,2-b2',3'
      e][1,4]diazepin-6-one (nevirapine), is investigated by semiempirical (MNDO, AMI
      and PM3) method, ab initio at the HF/3-21G and HF/6-31G** levels and density
      functional theory at the B3LYP/6-31G** level. The fully optimized structure and
      rotational potential of the nitrogen and carbon bond in the cyclopropyl ring were
      examined in detail. A similar geometrical minimum is obtained from all methods
      which shows an almost identical structure to the geometry of the molecule in the
      complex structure with HIV-1 reverse transcriptase. To get some information on
      the structure in solution, NMR chemical shift calculations were also performed by
      a density functional theory at the B3LYP/6-31G** level, using GIAO approximation.
      The calculated 1H-NMR and 13C-NMR spectra for the energy minimum geometry agree
      well with the experimental results, which indicated that the geometry of
      nevirapine in solution is very similar to that of the molecule in the inhibition
      complex. Furthermore, the obtained results are compared to the conformational
      studies of other non-nucleoside reverse transcriptase inhibitors and reveal a
      common agreement of the non-nucleoside reverse transcriptase inhibitors. The
      specific butterfly-like shape and conformational flexibility within the side
      chain of the non-nucleoside reverse transcriptase inhibitors play an important
      role inducing conformational change of HIV-1 reverse transcriptase structure and
      are essential for the association at the inhibition pocket.

PMID- 11989628
TI  - FP is named co-chair of presidential advisory council on HIV/AIDS.

PMID- 11989629
TI  - Physical examination for the Special Olympics.

PMID- 11989630
TI  - Promoting breastfeeding.

PMID- 11989631
TI  - Reducing barriers to breastfeeding.

PMID- 11989632
TI  - Imaging of abdominal aortic aneurysms.
AB  - Given the high rate of morbidity and mortality associated with abdominal aortic
      aneurysms (AAAs), accurate diagnosis and preoperative evaluation are essential
      for improved patient outcomes. Ultrasonography is the standard method of
      screening and monitoring AAAs that have not ruptured. In the past, aortography
      was commonly used for preoperative planning in the repair of AAAs. More recently,
      computed tomography (CT) has largely replaced older, more invasive methods.
      Recent advances in CT imaging technology, such as helical CT and CT angiography,
      offer significant advantages over traditional CT. These methods allow for more
      rapid scans and can produce three-dimensional images of the AAA and important
      adjacent vascular structures. Use of endovascular stent grafts has increased
      recently and is less invasive for the repair of AAAs in selected cases.
      Aortography and CT angiography can precisely determine the size and surrounding
      anatomy of the AAA to identify appropriate candidates for the use of endovascular
      stent grafts. Helical CT and CT angiography represent an exciting future in the
      preoperative evaluation of AAAs. However, this technology is not the standard of
      care because of the lack of widespread availability, the cost associated with
      obtaining new equipment, and the lack of universal protocols necessary for
      acquisition and reconstruction of these images.

PMID- 11989633
TI  - Prealbumin: a marker for nutritional evaluation.
AB  - Determining the level of prealbumin, a hepatic protein, is a sensitive and cost
      effective method of assessing the severity of illness resulting from malnutrition
      in patients who are critically ill or have a chronic disease. Prealbumin levels
      have been shown to correlate with patient outcomes and are an accurate predictor
      of patient recovery. In high-risk patients, prealbumin levels determined twice
      weekly during hospitalization can alert the physician to declining nutritional
      status, improve patient outcome, and shorten hospitalization in an increasingly
      cost-conscious economy.

PMID- 11989634
TI  - Cutaneous sarcoidosis: a dermatologic masquerader.
AB  - Sarcoidosis is a multisystem disease that may involve almost any organ system;
      therefore, it results in various clinical manifestations. Cutaneous sarcoidosis
      occurs in up to one third of patients with systemic sarcoidosis. Recognition of
      cutaneous lesions is important because they provide a visible clue to the
      diagnosis and are an easily accessible source of tissue for histologic
      examination. Because lesions can exhibit many different morphologies, cutaneous
      sarcoidosis is known as one of the "great imitators" in dermatology. Specific
      manifestations include papules, plaques, lupus pernio, scar sarcoidosis, and rare
      morphologies such as alopecia, ulcers, hypopigmented patches, and ichthyosis.
      Treatment of cutaneous lesions can be frustrating. For patients with severe
      lesions or widespread involvement, the most effective treatment is systemic
      glucocorticoids.

PMID- 11989635
TI  - Evaluation of dysuria in adults.
AB  - Dysuria, defined as pain, burning, or discomfort on urination, is more common in
      women than in men. Although urinary tract infection is the most frequent cause of
      dysuria, empiric treatment with antibiotics is not always appropriate. Dysuria
      occurs more often in younger women, probably because of their greater frequency
      of sexual activity. Older men are more likely to have dysuria because of an
      increased incidence of prostatic hyperplasia with accompanying inflammation and
      infection. A comprehensive history and physical examination can often reveal the
      cause of dysuria. Urinalysis may not be needed in healthier patients who have
      uncomplicated medical histories and symptoms. In most patients, however,
      urinalysis can help to determine the presence of infection and confirm a
      suspected diagnosis. Urine cultures and both urethral and vaginal smears and
      cultures can help to identify sites of infection and causative agents. Coliform
      organisms, notably Escherichia coli, are the most common pathogens in urinary
      tract infection. Dysuria can also be caused by noninfectious inflammation or
      trauma, neoplasm, calculi, hypoestrogenism, interstitial cystitis, or psychogenic
      disorders. Although radiography and other forms of imaging are rarely needed,
      these studies may identify abnormalities in the upper urinary tract when symptoms
      are more complex.

PMID- 11989636
TI  - Information from your family doctor. Dysuria.

PMID- 11989637
TI  - Feeding tubes in patients with severe dementia.
AB  - Patients with advanced dementia are among the most challenging patients to care
      for because they are often bedridden and dependent in all activities of daily
      living. Difficulty with eating is especially prominent and distresses family
      members and health care professionals. Health care professionals commonly rely on
      feeding tubes to supply nutrition to these severely demented patients. However,
      various studies have not shown use of feeding tubes to be effective in preventing
      malnutrition. Furthermore, they have not been demonstrated to prevent the
      occurrence or increase the healing of pressure sores, prevent aspiration
      pneumonia, provide comfort, improve functional status, or extend life. High
      complication rates, increased use of restraints, and other adverse effects
      further increase the burden of feeding tubes in severely demented patients.
      Feeding tubes should be avoided in many situations in which they are currently
      used. The preferable alternative to tube feeding is hand feeding. Though it may
      not be effective in preventing malnutrition and dehydration, hand feeding allows
      the maintenance of patient comfort and intimate patient care.

PMID- 11989638
TI  - ANCA-associated small-vessel vasculitis.
AB  - Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most
      common primary systemic small-vessel vasculitis to occur in adults. Although the
      etiology is not always known, the incidence of vasculitis is increasing, and the
      diagnosis and management of patients may be challenging because of its relative
      infrequency, changing nomenclature, and variability of clinical expression.
      Advances in clinical management have been achieved during the past few years, and
      many ongoing studies are pending. Vasculitis may affect the large, medium, or
      small blood vessels. Small-vessel vasculitis may be further classified as ANCA
      associated or non-ANCA-associated vasculitis. ANCA-associated small-vessel
      vasculitis includes microscopic polyangiitis, Wegener's granulomatosis, Churg
      Strauss syndrome, and drug-induced vasculitis. Better definition criteria and
      advancement in the technologies make these diagnoses increasingly common.
      Features that may aid in defining the specific type of vasculitic disorder
      include the type of organ involvement, presence and type of ANCA (myeloperoxidase
      ANCA or proteinase 3-ANCA), presence of serum cryoglobulins, and the presence of
      evidence for granulomatous inflammation. Family physicians should be familiar
      with this group of vasculitic disorders to reach a prompt diagnosis and initiate
      treatment to prevent end-organ damage. Treatment usually includes corticosteroid
      and immunosuppressive therapy.

PMID- 11989639
TI  - Screening for skin cancer: recommendations and rationale.

PMID- 11989640
TI  - Hemorrhoidectomy for thrombosed external hemorrhoids.
AB  - External hemorrhoids represent distended vascular tissue in the anal canal distal
      to the dentate line. Persons with thrombosed external hemorrhoids usually present
      with pain on standing, sitting or defecating. Acutely tender, thrombosed external
      hemorrhoids can be surgically removed if encountered within the first 72 hours
      after onset. Hemorrhoidectomy is performed through an elliptic incision over the
      site of thrombosis with removal of the entire diseased hemorrhoidal plexus in one
      piece. Caution must be exercised to avoid cutting into the muscle sphincter below
      the hemorrhoidal vessels. Infection after suture closure is rare secondary to the
      rich vascular network in the anal area. Stool softeners must be prescribed
      postoperatively to help prevent tearing at the suture line. Training and
      experience in general and skin surgery are necessary before the physician
      attempts this procedure unsupervised.

PMID- 11989641
TI  - Information from your family doctor. Hemorrhoidectomy for thrombosed external
      hemorrhoids.

PMID- 11989642
TI  - American College of Foot and Ankle Surgeons: Diagnosis and treatment of heel
      pain.

PMID- 11989643
TI  - FDA approves Procleix HIV-1/HCV assay.

PMID- 11989644
TI  - The day after genomic and proteomic era.

PMID- 11989645
TI  - Extracellular polyvalent cation block of slow Na+ channels in Xenopus laevis
      oocytes.
AB  - Sustained depolarization of the Xenopus oocyte membrane elicits a slowly
      activating Na+ current, thought to be due to the opening of sodium selective
      channels. These channels are induced to become voltage gated by the
      depolarization. They show unconventional gating properties and are insensitive to
      tetrodotoxin (TTX). The present study was undertaken to evaluate the effect of
      extracellular multivalent cations (Ca2+, Co2+, Cd2+, La3+, Mg2+, Mn2+, Ni2+, Sr2+
      and Zn2+) on these TTX-resistant channels, either on membrane potential responses
      or on current responses. Our data show that all the polyvalent cations used
      blocked Na+ channels in a concentration-dependent manner. The order of potency of
      the most efficient cations was Co2+ < Ni2+ < Cd2+ < Zn2+, the respective
      concentration required to cause a 50% decrease of Na+ current was 0.9+/-0.29;
      0.47+/-0.15; 0.36+/-0.09 and 0.06+/-0.02 mmol/l. The comparison of the activation
      curves from controls and after treatment with the cations indicated a shift
      towards more positive voltages. These results can be interpreted as due to the
      screening effect of divalent cations together with an alteration of the Na+
      channel gating properties. We also show that divalent cations blocked Na+
      channels in an open state without interfering with the induction mechanism of the
      channels. The possibility that cation block was due to a possible interaction
      between cations and SH-groups was investigated, but a sulphydryl alkylating
      reagent failed to abolish Zn2+ block.

PMID- 11989646
TI  - Effects of divalent cations on voltage-gated Ca2+ channels and depolarization
      induced [Ca2+], transients of freshly isolated pyramidal cells of the rat dorsal
      cochlear nucleus.
AB  - The effects of divalent cations on voltage-activated Ca2+ channels and
      depolarization-evoked cytoplasmic [Ca2+] elevations were studied in pyramidal
      neurones isolated from the dorsal cochlear nucleus of the rat. Ca2+ currents were
      recorded using the whole-cell configuration of the patch-clamp technique. 10
      micromol x l(-1) Cd2+ exerted a greater blocking effect on the high-voltage
      activated (HVA) currents than on the low-voltage activated (LVA) ones (decrease
      to 26.6+/-2.5% and to 87.8+/-2.1%, respectively). The blocking effect of 200
      micromol x l(-1) Cd2+ was more pronounced and the difference between the effect
      on the HVA and LVA currents became smaller (decrease to 11.7+/-2.1% and to 32.4+/
      2.7%, respectively). 200 micromol x l(-1) Ni2+ reduced the LVA component more
      effectively (to 77.6+/-5.4%) than the HVA one (to 86.9+/-2.6%). Cytoplasmic
      [Ca2+] changes were measured applying a fluorimetric technique (Fura-2). 10
      micromol x l(-1) Cd2+ decreased the peak values of 50 mmol x l(-1) K+
      depolarization-induced [Ca2]+i transients to 30.4+/-1.4% while 200 micromol x l(
      1) Cd2+ caused a drop to 2.5+/-0.2%. 200 micromol x l(-1) Ni2+ decreased the peak
      of the transients to 69.6+/-2.9%. Comparison of the blocking effects of divalent
      cations on Ca2+ currents and [Ca2+]i transients supports further the conclusion
      that the depolarization-induced [Ca2+]i changes are produced mainly by the
      activation of the HVA Ca2+ channels.

PMID- 11989647
TI  - Artificial membrane excitability revisited and implications for the gating of
      voltage-dependent ion channels.
AB  - Excitability phenomena in planar lipid bilayers doped with alamethicin and
      protamines have been first described by Mueller and Rudin (Nature 217, 713-719,
      1968). These properties are reinvestigated here with virtually solvent-free
      bilayers made of synthetic phospholipids doped with alamethicin charged component
      (Glu18) and protamine or other synthetic basic polypeptides. After retrieving the
      narrow set of experimental requisites allowing negative resistance and action
      potentials to develop, the potencies of different basic polypeptides were
      compared. Poly-arginines were found to be by far the most efficient. We also
      describe a transient increase of current amplitude upon addition of calcium that
      may reflect a lateral phase separation and conversely a gradual decrease of
      negative resistance due to tetrodotoxin, a potent sodium channel blocker.
      Functional modulations are correlated with conformational changes assayed in
      circular dichroism: alamethicin ellipticity in small unilamellar vesicles is
      markedly reduced upon protamine addition, only if the ionic strength is in the
      same low range that is compatible with regenerative conductance properties. These
      results are discussed in the framework of current models of ion channels gating.

PMID- 11989648
TI  - Carcinogenic and nephrotoxic alkaloids aristolochic acids upon activation by
      NADPH : cytochrome P450 reductase form adducts found in DNA of patients with
      Chinese herbs nephropathy.
AB  - Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has
      been found to be implicated in an unique type of renal fibrosis, designated
      Chinese herbs nephropathy (CHN), and associated with the development of
      urothelial cancer in CHN patients. Understanding, which enzymes are involved in
      AA activation and/or detoxication is important in the assessment of individual
      susceptibility of humans to this natural carcinogen. Using the nuclease P1
      version of the 32P-postlabeling assay we examined the ability of microsomal
      NADPH: CYP reductase to activate AA to metabolites forming DNA adducts. Renal and
      hepatic microsomes, containing NADPH:CYP reductase, generated AA-DNA adduct
      patterns reproducing those found in renal tissues in patients suffering from a
      renal fibrosis CHN and urothelial cancer. 7-(Deoxyadenosin-N6-yl)aristolactam I,
      7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II
      were identified as AA-DNA adducts formed by AAI. Two AA-DNA adducts, 7
      (deoxyguanosin-N2-yl) aristolactam II and 7- (deoxyadenosin-N6-yl) aristolactam
      II, were generated from AAII. According to the structures of the DNA adducts
      identified, nitroreduction is the crucial pathway in the metabolic activation of
      AA. The identity of NADPH: CYP reductase as activating enzyme in microsomes has
      been proved with different cofactors and an enzyme inhibitor. Alpha-lipoic acid,
      a selective inhibitor of NADPH: CYP reductase, significantly decreased the amount
      of the adducts formed by microsomes. Likewise, only a cofactor of the enzyme,
      NADPH, supported the DNA adduct formation of AAI and AAII, while NADH was
      ineffective. These results demonstrate an involvement of NADPH: CYP reductase in
      the activation pathway of AAI and AAII in the microsomal system. Moreover, using
      the purified enzyme, the participation of this enzyme in the formation of AA-DNA
      adducts was confirmed. The results presented here are the first report
      demonstrating a reductive activation of natural nitroaromatic compounds, AA, by
      NADPH: CYP reductase.

PMID- 11989649
TI  - Lesion of central part of the dorsomedial nucleus alters vasopressin but not
      corticotropin releasing hormone mRNA levels in rat hypothalamic paraventricular
      nucleus.
AB  - Functional significance of neural projections from the hypothalamic dorsomedial
      nucleus (DMN) to the paraventricular nucleus (PVN) was investigated using
      surgical lesion of the central part of the DMN. Under basal conditions, DMN
      lesion resulted in a decrease in magnocellular vasopressin (AVP) mRNA levels in
      the PVN, rise in pituitary proopiomelancortin (POMC) mRNA concentrations and
      elevated plasma corticosterone levels. Corticotropin-releasing hormone (CRH) mRNA
      levels remained unaffected. In sham operated animals, osmotic stress induced by
      hypertonic saline injection failed to modify AVP mRNA, but increased CRH and POMC
      mRNA levels and peripheral hormone release. The rise in CRH mRNA levels after
      osmotic stress was potentiated in DMN lesioned animals. Thus, the DMN
      participates in the control of hypothalamic peptide gene expression and pituitary
      adrenocorticotropic function.

PMID- 11989650
TI  - HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of
      the rat liver haptoglobin gene.
AB  - Expression of the haptoglobin (Hp) gene is liver specific and acute phase (AP)
      responsive. It was previously shown that transcriptional induction process of the
      rat Hp gene during turpentine induced AP response has been mediated by the liver
      nucleoprotein p29 which was shown to be homologous to the HMG-1 chromatin
      associated protein. The results presented in this report offered further evidence
      for the existence of structural and functional similarities between these two
      proteins implicating an involvement of HMG-1 in the regulation of the rat Hp gene
      transcription. By DNA binding assays we found the HMG-1 binding sites in the rat
      Hp gene cis-regulatory subelements A and C and revealed an increase in its DNA
      binding after induction of AP response. In view of our previous and here shown
      data we assume that this increase could be a consequence of AP-induced release of
      HMG-1 from the chromatin and subsequent increase in its nuclear amount.

PMID- 11989651
TI  - Tolperisone--a novel modulator of ionic currents in myelinated axons.
AB  - The actions of tolperisone on single intact Ranvier nodes of the toad Xenopus
      were investigated by means of the Hodgkin-Huxley formalism. Adding tolperisone to
      the bathing medium (100 micromol/l) caused the following fully reversible
      effects: 1. The sodium permeability P'Na was decreased by about 50% in a nearly
      potential-independent manner while the so-called sodium inactivation curve was
      shifted in the negative direction by about 3 mV. 2. The remaining parameters of
      the sodium system, i.e. m, taum and tauh, did not change. 3. The potassium
      permeability P'K decreased at strong depolarizing potentials (V > 60 mV); hence
      the permeability constant P(K) decreased by about 8%. However, weak
      depolarizations (V < 60 mV) caused P'K to increase by about 7%. 4. The potassium
      activation curve was shifted in the positive direction by about 9 mV and the
      exponent of n, b, was reduced from about 3.5 to about 1.5. Concentration-response
      relations for reduction of the sodium permeability constant PNa and of the
      potassium permeability constant P(K) yielded apparent dissociation constants of
      about 0.06 mmol/l and 0.32 mmol/l, respectively. The increase of P'K at V = 40
      mV, however, was largely concentration-independent. Our findings show that, in
      contrast to the prevailing view, tolperisone cannot be said to have a so-called
      lidocaine-like activity, because its effect on potassium permeability in the
      threshold region is fundamentally different from that of other known local
      anaesthetics. We infer that this effect, in combination with the decrease in
      sodium permeability, is responsible for the tendency of tolperisone to reduce
      excitability and hence for the antispastic action of tolperisone documented by
      clinical observations.

PMID- 11989652
TI  - Ischemia/Reperfusion-induced oxidative stress causes structural changes of brain
      membrane proteins and lipids.
AB  - Oxidative stress is a recognized factor of ischemia reperfusion injury. It shares
      damage of lipids (LPO) and proteins (PPO), and consequently might cause changes
      in activity of transport systems. Global 15 min ischemia followed by 2, 24 and 48
      hour reperfusion was induced by four-vessel occlusion in Wistar rats of both
      sexes. Levels of TBARS and conjugated dienes as parameters of LPO were analyzed
      in forebrain homogenates. Concentrations of total free sulfhydryl (SH) groups and
      emission spectra of tryptophan were measured to quantify PPO. Our results
      indicate that lipid peroxidation and protein oxidation occurs mainly during the
      period of reperfusion. However, significant increase in the level of conjugated
      dienes can be detected already after 15 min ischemia. Attack of proteins by free
      radicals leads to modification in structure of proteins seen as a decrease of
      free SH groups and tryptophan fluorescence. Ischemia/reperfusion induces
      formation of lipid peroxidation products as well as protein modifications.

PMID- 11989653
TI  - Reversal effect of specific inhibitors of extracellular-signal regulated protein
      kinase pathway on P-glycoprotein mediated vincristine resistance of L1210 cells.
AB  - Effect of specific inhibitors of extracellular-signal regulated protein kinase
      (ERK) pathway, PD98059 and U0126, on P-glycoprotein (Pgp)-mediated vincristine
      resistance of L1210/VCR cells was investigated. Both test inhibitors
      significantly reduced the survival of L1210/VCR cells in the presence of
      vincristine and this was associated with a decrease of LC50 values to vincristine
      from 2.65+/-0.43 to 0.67+/-0.28 micromol/l and to 0.69+/-0.09 micromol/l after
      treatment with 50 micromol/l PD98059 and 25 micromol/l UO126, respectively.
      Moreover, the effects of PD98059 are connected also with an increased
      intracellular accumulation of radiolabeled vincristine in resistant L1210/VCR
      cells in concentration dependent manner. The results of this study demonstrate
      that inhibitors of ERK signaling pathway are reversal agents of vincristine
      resistance in L1210/VCR cells. The precise mechanism of PD98059 and U0126 action
      in modulation of MDR is not resolved yet, but the role of ERK-mediated
      phosphorylation cascade could be considered.

PMID- 11989654
TI  - Reduction of 1-methyl-1-nitrosourea-induced mammary gland carcinoma by in vivo
      application of immunostimulatory CpG motifs in Sprague-Dawley rats.
AB  - In the present work the role of 13-cis retinoic acid and CpG
      oligodeoxynucleotides (CpG-ODN) in a 1-methyl-1-nitrosourea (MNU)-induced mammary
      gland carcinoma animal model was investigated. Treatment with both components,
      applied either alone or in combination, induced a significant decrease of the
      tumour burden and the volume of tumours only in rats that received CpG-ODN (p =
      0.046, compared to the MNU control group). The data indicate that the Th-1 biased
      immunostimulatory capacities of CpG motifs may play a significant role in
      induction of protective immune responses against mammary gland tumours in Sprague
      Dawley rats.

PMID- 11989655
TI  - Cloning of anti-lPS factor cDNA from Tachypleus tridentatus, expression in Bombyx
      mori larvae and its biological activity in vitro.
AB  - In this article we report the cloning and expression of a cDNA encoding
      Tachypleus anti-lipopolysaccharide (LPS) factor, which is of interest for use as
      a potential inhibitor of the common core subunit of Gram-negative bacterial
      endotoxins. First, two degenerate primers were designed based on the sequence
      homology of anti-LPS factors purified from different species of horseshoe crab.
      The total RNA was extracted from amebocytes of Tachypleus tridentatus. The cDNA
      was then obtained by using the RT-PCR methods. Second, the cDNA of Tachypleus
      anti-LPS factor (TALF) was expressed in Bombyx mori larvae using baculovirus
      expression system, which showed a yield of up to 600 mg/L. Last, we determined
      the biological activity of the recombinant proteins by LPS neutralization assay
      and bacteriostatic assay in vitro.

PMID- 11989656
TI  - Quantitative analysis of gene expression by reverse transcription polymerase
      chain reaction and capillary electrophoresis with laser-induced fluorescence
      detection.
AB  - There has been a dramatic expansion of DNA sequence information compiled over the
      past several years for a variety of eukaryotic and prokaryotic genomes.
      Accompanying this increase in knowledge of genomic structure and organization has
      been a growing interest in studying the function of individual genes including
      regulation of their expression. A number of methods such as Northern blotting,
      ribonuclease protection assay, and hybridization arrays have been developed to
      analyze gene expression at the transcriptional (mRNA) level. Although
      quantitative estimates of mRNA transcripts can be obtained from each of these
      methods, oftentimes they lack sufficient sensitivity or the methodology is too
      costly or too labor-intensive to be applied to the analysis of a large number of
      samples. The most sensitive method for analyzing gene expression at the mRNA
      level involves the combination of reverse transcription and polymerase chain
      reaction (RT-PCR). However, in order to provide accurate quantitative estimates
      of gene expression, a rapid and efficient method is required for separation and
      detection of the double-stranded DNA (dsDNA) products of RT-PCR. Recent advances
      in capillary electrophoresis with laser-induced fluorescence detection (CE/LIF)
      have made this method suitable for the automated analysis of large numbers of RT
      PCR samples. An overview of the application of CE/LIF to quantitative analysis of
      gene expression by RT-PCR is presented along with selected protocols and
      examples. Both relative-quantitative (RQ) and quantitative-competitive (QC)
      approaches to RT-PCR are discussed in conjunction with the use of CE/LIF for
      rapid and accurate quantitative analysis of PCR products.

PMID- 11989657
TI  - Flexprep: scale-flexible rapid plasmid preparation for analysis of recombinant
      clones.
AB  - A scale-flexible and cost-efective protocol for plasmid preparation is described
      to cover miniprep and midiprep scale work in a microcentriguge format for
      analysis of recombinant clones, this protocol relies on a modified alkaline lysis
      of Escherichia coli cells and subsequent purification of plasmid DNA with no
      organic extraction and alcohol precipitation. It can process up to 20 mL of E.
      coli cells carrying 3-10 kbp plasmid vectors in < 10 min. Flexprep delivers
      sufficient yield and purity of plasmid DNA for routine applications including
      restriction enzyme digestion and fluorescent automated sequencing.

PMID- 11989658
TI  - Differential gene expression during somatic embryogenesis in Coffea arabica L.,
      revealed by RT-PCR differential display.
AB  - Molecular and biochemical studies of somatic embryogenesis may help to shed light
      on the mechanisms governing this phenomenon. In this article, a differential
      display analysis approach was employed to investigate the changes taking place
      during the induction of somatic embryogenesis in leaf explants and suspension
      cultures of coffee. Cloned fragments show homologies to several proteins reported
      in databases, but only one has previously been described as regulated during
      somatic embryogenesis. By a reverse dot blot modification, the expression pattern
      of such fragments was evaluated.

PMID- 11989659
TI  - A single buffer that universally serves both restriction digestion and loading.
AB  - Restriction digestion is routinely performed in a buffer compatible with the
      restriction enzyme used. To load the samples on agarose gels for electrophoresis
      it is then necessary to add a loading buffer. A 10X loading buffer is often used,
      and consists of a dye to track the electrophoresis and a dense solution so that
      the digestion mixture sinks into the well. We describe a new buffer, which acts
      as a universal digestion buffer as well as a loading buffer. This avoids double
      handling of samples, which wastes both time and consumables. Importantly, the
      efficiency of digestion was found not to be significantly decreased in this new
      buffer.

PMID- 11989660
TI  - Validation of biopharmaceutical purification processes for virus clearance
      evaluation.
AB  - Any biopharmaceutical product that has involved the use of animal-derived
      material during the manufacturing process has the potential to be contaminated
      with animal viruses. To ensure safety of these products, extensive testing is
      performed on the starting materials, such as the cell banks, and on the raw
      materials used in manufacture. Additional testing is also performed at various
      stages of production and, in some cases, on the final product as well. Because of
      inherent limitations in direct testing methods, the capacity of the downstream
      purification process to remove/inactivate potential viral contaminants is also
      studied to give an extra degree of assurance that the final product will be free
      of infectious viruses.

PMID- 11989661
TI  - Angiogenesis and the unique nature of tumor matrix.
AB  - In this article we consider the factors responsible for the unique nature of the
      pericellular matrix of solid tumors and we discuss the role of alterations of
      tumor blood vessel structure. We examine the role of VEGF (vascular endothelial
      growth factor), a factor controlling permeability of capillaries, plasma protein
      extravasation, and the formation of a fibrin barrier. We discuss how this barrier
      could be destroyed by metalloproteinases bound on the surface of endothelial
      cells migrating through the matrix and how these enzymes are responsible for the
      activation of gelatinases that destroy basement membranes. The process called
      tubulogenesis, which gives rise to hyperpermeable tumor capillaries, will also be
      described. Alterations of the blood vessel structure leading to hypoxia of the
      matrix, and accumulation of plasma proteins and of blood cells will be treated.
      Finally, we review some of the strategies that might exploit this knowledge about
      the nature of the tumoral matrix for designing novel anticancer treatments.

PMID- 11989662
TI  - The first reporter gene assay on living cells: green fluorescent protein as
      reporter gene for the investigation of Gi-protein coupled receptors.
AB  - Reporter gene assay systems are important tools for the investigation of G
      protein coupled receptors and their interaction with ligands. Here, we describe a
      novel reporter gene assay system for the investigation of Gi-protein coupled
      receptors in living cells. For the first time green fluorescent protein (GFP) was
      used as reporter gene under the transcriptional control of cAMP-response elements
      (CREs). Three different reporter gene vectors with increasing numbers of CREs
      were cloned and GFP expression was investigated after forskolin stimulation.
      Furthermore, the novel reporter system was successfully applied to the
      neuropeptide Y (NPY) rY5 receptor subtype, a Gi-protein coupled receptor. Our
      data clearly demonstrate dose-dependent GFP expression for NPY. Furthermore,
      receptor subtype selectivity of well characterized NPY analog could be proven for
      the NPY rY5 receptor. The great advantage of the method is that no cell lysis is
      required and assays can be performed on living cells. Accordingly, in vitro
      testing of agonist gets faster and significantly more convenient.

PMID- 11989664
TI  - UDP-galactose 4-epimerase from Escherichia coli: equilibrium unfolding studies.
AB  - UDP-galactose 4-epimerase from Escherichia coli is a homodimer of 39 kDa subunit
      with non-covalently bound NAD acting as cofactor. The enzyme can be reversibly
      reactivated after denaturation and dissociation using 8 M urea at pH 7.0. There
      is a strong affinity between the cofactor and the refolded molecule as no
      extraneous NAD is required for its reactivation. Results from equilibrium
      denaturation using parameters like catalytic activity, circular-dichroism,
      fluorescence emission (both intrinsic and with extraneous fluorophore 1-aniline 8
      naphthalene sulphonic acid), 'reductive inhibition' (associated with orientation
      of NAD on the native enzyme surface), elution profile from size-exclusion HPLC
      and light scattering have been compiled here. These show that inactivation,
      integrity of secondary, tertiary and quaternary structures have different
      transition mid-points suggestive of non-cooperative transition. The unfolding
      process may be broadly resolved into three parts: an active dimeric holoenzyme
      with 50% of its original secondary structure at 2.5 M urea; an active monomeric
      holoenzyme at 3 M urea with only 40% of secondary structure and finally further
      denaturation by 6 M urea leads to an inactive equilibrium unfolded state with
      only 20% of residual secondary structure. Thermodynamical parameters associated
      with some transitions have been quantitated. The results have been discussed with
      the X-ray crystallographic structure of the enzyme.

PMID- 11989663
TI  - Antibodies for neoplastic disease solid tumors.

PMID- 11989665
TI  - Limited proteolysis by trypsin influences activity of maize phosphoenolpyruvate
      carboxylase.
AB  - Maize phosphoenolpyruvate carboxylase (PEPC) was rapidly and completely
      inactivated by very low concentrations of trypsin at 37 degrees C. PEP+Mg2+ and
      several other effectors of PEP carboxylase offered substantial protection against
      trypsin inactivation. Inactivation resulted from a fairly specific cleavage of 20
      kDa peptide from the enzyme subunit. Limited proteolysis under catalytic
      condition (in presence of PEP, Mg2+ and HCO3) although yielded a truncated
      subunit of 90 kDa, did not affect the catalytic function appreciably but
      desensitized the enzyme to the effectors like glucose-6-phosphate glycine and
      malate. However, under non-catalytic condition, only malate sensitivity was
      appreciably affected. Significant protection of the enzyme activity against
      trypsin during catalytic phase could be either due to a conformational change
      induced on substrate binding. Several lines of evidence indicate that the
      inactivation caused by a cleavage at a highly conserved C-terminal end of the
      subunit.

PMID- 11989666
TI  - Equilibrium denaturation of buffalo pituitary growth hormone.
AB  - To understand the structural properties of buffalo growth hormone (buGH), the
      equilibrium denaturation using guanidinium chloride (GdmCl) was carried out and
      was monitored by ultraviolet absorption spectroscopy, intrinsic fluorescence
      spectroscopy, far UV-circular dichroism and size-exclusion chromatography. The
      normalized denaturation transition curves for each of the above methods were not
      coincident, showing that buGH does not follow a simple two state folding
      mechanism. Further, size-exclusion chromatography also showed the presence of an
      associated intermediate during the unfolding of buGH. It was observed that in
      buGH, denaturation resulted in an initial disruption of the tertiary structure,
      whereas the secondary structure and the degree of compactness were disrupted at a
      higher concentration of the denaturant. This suggests that buGH follows the
      hierarchical model of protein folding.

PMID- 11989667
TI  - Physico-chemical characterization of growth hormone from water buffaloes (Bubalus
      bubalis).
AB  - A purified preparation of growth hormone from pituitaries of water buffaloes
      (Bubalus bubalis) has been extensively characterized with regard to physico
      chemical properties. The molecular size of buffalo GH (buGH) by electrospray
      ionization mass spectroscopy (ES-MS) was found to be 21394.00+/-8.44Da and its
      stokes radius was determined as 2.3 nm. Size heterogeneity in buffalo GH was
      checked both by electrophoresis and molecular sieve chromatography using 125I
      labelled buffalo GH. Similar size heterogeneity was found in standard
      preparations of ovine and bovine growth hormones. Isoelectric focussing and
      chromatofocussing indicated charge heterogeneity in buffalo GH preparation. Major
      charge isoforms having pI of 7.2, 7.7 and minor forms in the pI range of 5.7 to
      7.0 were found. Lectin chromatography on Concanavalin A matrix showed that less
      than 1% of buffalo GH was glycosylated. Heterogeneity in NH2-terminal sequence
      was also observed, with alanine, phenylalanine and methionine as the NH2-terminal
      residues as checked by dansyl and DABITC methods. Estimation of tryptophan
      residue indicated that a single tryptophan residue was present. Ellman's method
      showed presence of two disulfide bridges per mole of buffalo GH. Intrinsic
      fluorescence spectrum of buffalo GH exhibited lambda emission maximum at 337 nm.
      UV-CD spectrum showed that almost 48% of the secondary structure of buGH was
      constituted by alpha-helicity. The T(M) of buGH as determined by differential
      scanning calorimetric (DSC) studies was found to be 63 degrees C.

PMID- 11989668
TI  - Buffalo plasma fibronectin: a physico-chemical study.
AB  - Plasma fibronectin (FN) of buffalo (Babulis babulis) was purified to apparent
      homogeneity, using gelatin-Sepharose and heparin-Sepharose affinity columns. It
      was found to have two subunits of molecular mass 246 kDa and 228 kDa, on SDS-gel.
      Its immunological cross-reactivity with anti-human plasma FN was confirmed by
      Western blotting. The amino acid composition was found to be similar to that of
      human and bovine plasma FNs. Buffalo plasma FN contained 2.23% neutral hexoses
      and 1.18% sialic acids. No titrable sulfhydryl group could be detected in the
      absence of denaturant. Reaction with DTNB indicated 3.4 sulfhydryl groups in the
      molecule, whereas BDC-OH titration gave a value of 3.8 -SH groups in buffalo
      plasma FN. Stoke's radius, intrinsic viscosity, diffusion coefficient and
      frictional ratio indicated that buffalo plasma FN did not have a compact globular
      conformation at physiological pH and ionic strength. Molecular dimensions
      (average length, 120 nm; molar mass to length ratio, 3950 nm(-1) and mean
      diameter, 2.4 nm) as revealed by rotary shadowing electron microscopy further
      supported the extended conformation of buffalo plasma FN. These results show that
      buffalo plasma FN has similar properties as that of human plasma FN.

PMID- 11989669
TI  - Non-coordinate expression of closely linked mouse casein genes.
AB  - Expression levels of five mouse casein genes were analysed in the mammary gland
      of virgin, pregnant and lactating mice. We have already shown that the five
      murine casein genes are arranged in the order, alpha-beta-gamma-epsilon-kappa in
      a tandem array, very close to each other in a 250 kb DNA fragment of mouse
      genome. Northern blot analysis showed that, of the calcium-sensitive casein
      genes, the epsilon casein gene is expressed only during lactation unlike the
      alpha, beta and gamma casein genes which are expressed during pregnancy and
      lactation. Even though the alpha, beta and gamma genes exhibited a co-ordinated
      expression pattern from mid to the later stages of pregnancy, the mRNA levels
      varied considerably (60, 90 and 100% respectively) by the onset of lactation. The
      mRNA level of the calcium-insensitive kappa casein gene increased from mid
      pregnancy but at a lower rate and reached approximately 60% by the first day of
      lactation. Considering the locations and closeness of the casein genes, a non
      coordinate expression profile is exhibited by the mouse casein genes,
      particularly the epsilon casein gene.

PMID- 11989670
TI  - Effect of a water soluble derivative of alpha-tocopherol on radiation response of
      Saccharomyces cerevisiae.
AB  - The radioprotection conferred by a highly water soluble glucose derivative of
      alpha-tocopherol, namely, 2-(alpha-D-glucopyranosyl) methyl-2,5,7,8
      tetramethylchroman-6-ol (TMG) in Saccharomyces cerevisiae was studied. Cells
      grown in standard YEPD-agar medium and irradiated in the presence of TMG showed a
      concentration dependent higher survival up to 10 mM of TMG in comparison to cells
      irradiated in distilled water. Treatment of TMG to cells given either before or
      immediately after irradiation but not during irradiation, had no effect on their
      radiation response. S. cerevisiae strain LP1383 (rad52) which is defective in
      recombination repair showed enhanced radioresistance only when subjected to
      irradiation in presence of TMG. Cells of rad52 strain grown in the medium
      containing TMG showed a radiation response similar to that of cells grown in the
      medium without TMG. The nature of TMG dependent enhanced radioresistance was
      studied by scoring the mutations in the strain D-7, which behaved like wild type
      strain in complete medium, at trp and ilv loci. Our study indicated that TMG
      confers radioresistance in S. cerevisiae possibly by two mechanisms viz. (i), by
      eliminating radiation induced reactive free radicals when the irradiation is
      carried out in the presence of TMG and (ii), by activating an error prone repair
      process involving RAD52 gene, when the cells are grown in the medium containing
      TMG.

PMID- 11989671
TI  - Effect of gamma-irradiation on H3 histone and DNA in solution.
AB  - Three methods, namely, absorbance of colour by reaction with Folin-Ciocalteau
      reagent, UV absorbance and fluorescence intensity measurements for detection of
      H3 histone in 0.15 M standard saline citrate (SSC) solution were compared.
      Maximum sensitivity was found with the Folin-Ciocalteau method. Effect of varying
      pH and of gamma- radiation on H3 histone and on interaction of H3 histone with
      DNA were studied. For this, solutions of H3 histone in SSC, in 0.9% NaCl, H3
      histone + DNA in 0.9% NaCl were subjected to varying pH (1-10) and gamma-
      radiation (dose 10-50 Gy) and lambda(max) and Alambda(max) were monitored. From
      the molar ratios of histone and DNA in the complex, it was observed that at gamma
      -radiation dose of 50 Gy and pH 8.54, there was a depletion of 6-8 microg/ml of
      histone from the histone-DNA complex.

PMID- 11989672
TI  - Role of liquid membrane phenomenon in biological actions of ACE inhibitors,
      captopril and lisinopril.
AB  - The liquid membrane phenomenon in angiotensin converting enzyme (ACE) inhibitors
      namely, captopril and lisinopril has been studied. Hydraulic permeability data
      have been obtained to demonstrate the existence of the liquid membrane in series
      with a supporting membrane generated by the ACE inhibitors. Data on the transport
      of the relevant permeants in presence of the liquid membrane formed by ACE
      inhibitors indicate that liquid membrane phenomenon is likely to play a
      significant role in the action of ACE inhibitors.

PMID- 11989673
TI  - Conformational study of peptides containing dehydrophenylalanine: helical
      structures without hydrogen bond.
AB  - The conformational behaviour of deltaZPhe has been investigated in the model
      dipeptide Ac-deltaZPhe-NHMe and in the model tripeptides Ac-X-deltaZPhe-NHMe with
      X=Gly,Ala,Val,Leu,Abu,Aib and Phe and is found to be quite different. In the
      model tripeptides with X=Ala,Val,Leu,Abu,Phe the most stable structure
      corresponds to phi1=-30 degrees, psi1=120 degrees and phi2=psi2=30 degrees. This
      structure is stabilized by the hydrogen bond formation between C=O of acetyl
      group and the NH of the amide group, resulting in the formation of a 10-membered
      ring but not a 3(10) helical structure. In the peptides Ac-Aib-deltaZPhe-NHMe and
      Ac-(Aib-deltaZPhe)3-NHMe, the helical conformers with phi = +/-30 degrees, psi =
      +/-60 degrees for Aib residue and phi=psi= +/-30 degrees for deltaZPhe are
      predicted to be most stable. The computational studies for the positional
      preferences of deltaZPhe residue in the peptide containing one deltaZPhe and nine
      Ala residues reveal the formation of a 3(10) helical structure in all the cases
      with terminal preferences for deltaZPhe. The conformational behaviour of Ac
      (deltaZPhe)n-NHMe with n< or =4 is predicted to be very labile. With n > 4,
      degenerate conformational states with phi,psi values of 0 degrees +/- 90 degrees
      adopt helical structures which are stabilized by carbonyl-carbonyl interactions
      and the N-H-pi interactions between the amino group of every deltaZPhe residue
      with one C-C edge of its own phenyl ring. The results are in agreement with the
      experimental finding that screw sense of helix for peptides containing deltaZPhe
      residues is ambiguous in solution. The helical structures stabilized by hydrogen
      bond formation are found to be at least 3kCalmol(-1) less stable. Conformational
      studies have also been carried out for the peptide Ac-(deltaEPhe)6-NHMe and the
      peptide Ac-deltaAla-(deltaZPhe)6-NHMe containing deltaAla residue at the N
      terminal. The N-H-pi interactions are absent in peptide Ac-(deltaEPhe)6-NHMe.

PMID- 11989675
TI  - Interpretation of the results of common principal components analyses.
AB  - Common principal components (CPC) analysis is a new tool for the comparison of
      phenotypic and genetic variance-covariance matrices. CPC was developed as a
      method of data summarization, but frequently biologists would like to use the
      method to detect analogous patterns of trait correlation in multiple populations
      or species. To investigate the properties of CPC, we simulated data that reflect
      a set of causal factors. The CPC method performs as expected from a statistical
      point of view, but often gives results that are contrary to biological intuition.
      In general, CPC tends to underestimate the degree of structure that matrices
      share. Differences of trait variances and covariances due to a difference in a
      single causal factor in two otherwise identically structured datasets often cause
      CPC to declare the two datasets unrelated. Conversely, CPC could identify
      datasets as having the same structure when causal factors are different.
      Reordering of vectors before analysis can aid in the detection of patterns. We
      urge caution in the biological interpretation of CPC analysis results.

PMID- 11989676
TI  - A complexity drain on cells in the evolution of multicellularity.
AB  - A hypothesis has been advanced recently predicting that, in evolution, as higher
      level entities arise from associations of lower-level organisms, and as these
      entities acquire the ability to feed, reproduce, defend themselves, and so on,
      the lower-level organisms will tend to lose much of their internal complexity
      (McShea 2001a). In other words, in hierarchical transitions, there is a drain on
      numbers of part types at the lower level. One possible rationale is that the
      transfer of functional demands to the higher level renders many part types at the
      lower level useless, and thus their loss in evolution is favored by selection for
      economy. Here, a test is conducted at the cell level, comparing numbers of part
      types in free-living eukaryotic cells (protists) and the cells of metazoans and
      land plants. Differences are significant and consistent with the hypothesis,
      suggesting that tests at other hierarchical levels may be worthwhile.

PMID- 11989677
TI  - A comprehensive model of mutations affecting fitness and inferences for
      Arabidopsis thaliana.
AB  - As the ultimate source of genetic variation, spontaneous mutation is essential to
      evolutionary change. Theoretical studies over several decades have revealed the
      dependence of evolutionary consequences of mutation on specific mutational
      properties, including genomic mutation rates, U, and the effects of newly arising
      mutations on individual fitness, s. The recent resurgence of empirical effort to
      infer these properties for diverse organisms has not achieved consensus.
      Estimates, which have been obtained by methods that assume mutations are
      unidirectional in their effects on fitness, are imprecise. Both because a general
      approach must allow for occurrence of fitness-enhancing mutations, even if these
      are rare, and because recent evidence demands it, we present a new method for
      inferring mutational parameters. For the distribution of mutational effects, we
      retain Keightley's assumption of the gamma distribution, to take advantage of the
      flexibility of its shape. Because the conventional gamma is one sided,
      restricting it to unidirectional effects, we include an additional parameter,
      rho, as an amount it is displaced from zero. Estimation is accomplished by Markov
      chain Monte Carlo maximum likelihood. Through a limited set of simulations, we
      verify the accuracy of this approach. We apply it to analyze data on two
      reproductive fitness components from a 17-generation mutation-accumulation study
      of a Columbia accession of Arabidopsis thaliana in which 40 lines sampled in
      three generations were assayed simultaneously. For these traits, U
      approximately/= 0.1-0.2, with distributions of mutational effects broadly
      spanning zero, such that roughly half the mutations reduce reproductive fitness.
      One evolutionary consequence of these results is lower extinction risks of small
      populations of A. thaliana than expected from the process of mutational meltdown.
      A comprehensive view of the evolutionary consequences of mutation will depend on
      quantitatively accounting for fitness-enhancing, as well as fitness-reducing,
      mutations.

PMID- 11989678
TI  - Hardly a relict: freezing and the evolution of vesselless wood in Winteraceae.
AB  - The Winteraceae are traditionally regarded as the least-specialized descendents
      of the first flowering plants, based largely on their lack of xylem vessels.
      Since vessels have been viewed as a key innovation for angiosperm
      diversification, Winteraceae have been portrayed as declining relicts, limited to
      wet forest habitats where their tracheid-based wood does not impose a significant
      hydraulic constraints. In contrast, phylogenetic analyses place Winteraceae among
      angiosperm clades with vessels, indicating that their vesselless wood is derived
      rather than primitive, whereas extension of the Winteraceae fossil record into
      the Early Cretaceous suggests a more complex ecological history than has been
      deduced from their current distribution. However, the selective regime and
      ecological events underlying the possible loss of vessels in Winteraceae have
      remained enigmatic. Here we examine the hypothesis that vessels were lost as an
      adaptation to freezing-prone environments in Winteraceae by measuring the
      responses of xylem water transport to freezing for a diverse group of Winteraceae
      taxa as compared to Canella winterana (Canellaceae, a close relative with
      vessels) and sympatric conifer taxa. We found that mean percent loss of xylem
      water transport capacity following freeze-thaw varied from 0% to 6% for
      Winteraceae species from freezing-prone temperate climates and approximately 20%
      in those taxa from tropical (nonfreezing) climates. Similarly, conifers exhibit
      almost no decrease in xylem hydraulic conductivity following freezing. In
      contrast, water transport in Canella stems is nearly 85% blocked after freeze
      thaw. Although vessel-bearing wood of Canella possesses considerably
      greaterhydraulic capacity than Winteraceae, nearly 20% of xylem hydraulic
      conductance remains, a value that is comparable to the hydraulic capacity of
      vesselless Winteraceae xylem, if the proportion of hydraulic flow through vessels
      (modeled as ideal capillaries) is removed. Thus, the evolutionary removal of
      vessels may not necessarily require a deleterious shift to an ineffective
      vascular system. By integrating Winteraceae's phylogenetic relationships and
      fossil history with physiological and ecological observations, we suggest that,
      as ancestors of modern Winteraceae passed through temperate conditions present in
      Southern Gondwana during the Early Cretaceous, they were exposed to selective
      pressures against vessel-possession and returned to a vascular system relying on
      tracheids. These results suggest that the vesselless condition is advantageous in
      freezing-prone areas, which is supported by the strong bias in the ecological
      abundance of Winteraceae to wet temperate and tropical alpine habitats, rather
      than a retained feature from the first vesselless angiosperms. We believe that
      vesselless wood plays an important role in the ecological abundance of
      Winteraceae in Southern Hemisphere temperate environments by enabling the
      retention of leaves and photosynthesis in the face of frequent freeze-thaw
      events.

PMID- 11989679
TI  - Character release following extinction in a Caribbean reef coral species complex.
AB  - The Pleistocene extinction of the widespread organ-pipe Montastraea coral had
      measurable morphological and ecological effects on surviving lineages of the
      Montastraea "annularis" species complex. Extinction of the organ-pipe Montastraea
      occurred after more than 500,000 years of dominance in the shallow-water reef
      habitat of Barbados. Extinction resulted in a morphological shift of the columnar
      Montastraea lineage from thick to thin columns in modern reef environments.
      Pleistocene colonies of the columnar morphotype sympatric with organ-pipe
      Montastraea showed greater column widths than those in allopatry. We subjected
      our data to a number of criteria for interpreting the morphological shift as
      character release following lifting of competitive pressure after extinction. The
      morphological differences do not appear to be due either to chance or to physical
      properties of the marine environment. Differential local extinction and
      recolonization of four members of the species complex did not occur on Barbados,
      so that the species coexisted and appear to have coevolved between more than
      600,000 and 82,000 years ago. The morphological shift is related to coral growth
      form and growth rate, and thus reflects the acquisition of a primary resource in
      corals--light. Character release occurred at the same oceanic Caribbean island
      (Barbados) where environments have fluctuated with similar variance throughout
      the period of coexistence. Not only has competition among living members of the
      Montastraea "annularis" species complex been convincingly demonstrated, but
      trends in relative abundance among fossil members of the species complex strongly
      suggest that a competitive hierarchy was operating during their Pleistocene
      coexistence on Barbados. We also observed an ecological analogue to character
      release on another Caribbean island. Curacao. The distribution and abundance of
      living columnar M. annularis s.s. and massive M. faveolata from the leeward reef
      crest in Curacao is greater now than in the Pleistocene, when organ-pipe
      Montastraea dominated this shallow-water reef habitat. Extinction of the faster
      growing, shallow-water organ-pipe Montastraea resulted in higher abundance of the
      columnar Montastraea lineage in shallow-water habitats, where it shifted its
      morphology to one adapted to high light levels. The species extinction released
      surviving lineages from a competitive network that had resulted in lower rank
      abundance in the Pleistocene community and enhanced abundance of both columnar M.
      annularis s.s. and M. faveolata in modern communities. Full validation of our
      interpretation of character release must await experiments that demonstrate
      whether phenotypic differences between populations have a genetic basis. However,
      we believe the results of this study point to the important, yet heretofore
      neglected, role that biological interactions have played in the evolution of
      closely related reef coral species.

PMID- 11989680
TI  - A simple test: evaluating explanations for the relative simplicity of the
      Edwardsiidae (Cnidaria: Anthozoa).
AB  - Many members of the cnidarian subclass Zoantharia (sea anemones, corals, and
      their allies) pass through a larval stage with eight complete mesenteries and
      without posterior musculature. This larva is usually transient, developing into
      an adult with 12 or more mesenteries. The adults of one family of sea anemones,
      the Edwardsiidae, bear the larval number and arrangement of mesenteries and lack
      the pedal disc seen in other sea anemones. The morphology of the Edwardsiidae has
      been interpreted in a number of ways: (1) the Edwardsiidae are the most basal
      extant zoantharian, having diverged before the evolution of additional
      mesenteries and basal musculature; (2) they are relatively advanced sea anemones
      that have secondarily simplified because they burrow in sand or mud rather than
      attaching to a hard substrate; or (3) edwardsiids are derived anemones that have
      retained a juvenile morphology through paedomorphosis. Phylogenetic analyses of
      small subunit ribosomal gene sequences reveal that the Edwardsiidae are derived
      zoantharians, nested within sea anemones. None of the proposed explanations fully
      explain the edwardsiid's body plan; edwardsiid anatomy is a mosaic of retained
      primitive and derived features. The results of the present study provide insight
      into zoantharian phylogeny and illustrate how phylogenetic tests can be used to
      study the evolution of cnidarian body plans.

PMID- 11989681
TI  - Sex-ratio bias and clonal reproduction in the brittle star Ophiactis savignyi.
AB  - Although the sex ratios of many groups conform to Fisher's (1930) prediction that
      parents should invest equally in daughters and sons, a number of taxa are
      characterized by excesses of one gender. A variety of mechanisms may lead to sex
      ratio biases, but in organisms that reproduce clonally as well as sexually,
      gender differences in the rate of cloning could drive the development of sex
      ratio biases. In this study, I demonstrate that males of the clonal brittle star
      Ophiactis savignyi were significantly more likely to divide than females and that
      the magnitude of this difference was sufficient to explain the consistent and
      significant excess of males in natural populations. Females were significantly
      more likely to lose sexual reproductive capabilities following division, and this
      greater cost associated with division may explain why females are less likely to
      divide. Gender differences in mortality rates are unlikely to explain the excess
      of males in this species. Because of their potential influence on the operational
      sex ratio, gender differences in division rates may have important ecological and
      evolutionary implications including effects on the direction and strength of
      selection.

PMID- 11989682
TI  - Strong inbreeding depression in a Daphnia metapopulation.
AB  - The deleterious effects of inbreeding have long been known, and inbreeding can
      increase the risk of extinction for local populations in metapopulations.
      However, other consequences of inbreeding in metapopulations are still not well
      understood. Here we show the presence of strong inbreeding depression in a
      rockpool metapopulation of the planktonic freshwater crustacean Daphnia magna,
      which reproduces by cyclical parthenogenesis. We conducted three experiments in
      real and artificial rockpools to quantify components of inbreeding depression in
      the presence and the absence of competition between clonal lines of selfed and
      outcrossed genotypes. In replicated asexual populations, we recorded strong
      selection against clones produced by selfing in competition with clones produced
      by outcrossing. In contrast, inbreeding depression was much weaker in single
      clone populations, that is, in the absence of competition between inbred and
      outbred clones. The finding of a competitive advantage of the outbred genotypes
      in this metapopulation suggests that if rockpool populations are inbred, hybrid
      offspring resulting from crosses between immigrants and local genotypes might
      have a strong selective advantage. This would increase the effective gene flow in
      the metapopulation. However, the finding of low inbreeding depression in the
      monoclonal populations suggests that inbred and outbred genotypes might have
      about equal chances of establishing new populations.

PMID- 11989683
TI  - Divergence of mitochondrial dna is not corroborated by nuclear dna, morphology,
      or behavior in Drosophila simulans.
AB  - We ask whether the observed mitochondrial DNA (mtDNA) population subdivision of
      Drosophila simulans is indicative of organismal structure or of specific
      processes acting on the mitochondrial genome. Factors either intrinsic or
      extrinsic to the host genome may influence the evolutionary dynamics of mtDNA.
      Potential intrinsic factors include adaptation of the mitochondrial genome and of
      nucleomitochondrial gene complexes specific to the local environment. An
      extrinsic force that has been shown to influence mtDNA evolution in invertebrates
      is the bacterial endosymbiont Wolbachia. Evidence presented in this study
      suggests that mtDNA is not a good indicator of organismal subdivision in D.
      simulans. Furthermore, there is no evidence to suggest that Wolbachia causes any
      reduction in nuclear gene flow in this species. The observed differentiation in
      mtDNA is not corroborated by data from NADH: ubiquinone reductase 75kD subunit
      precursor or the Alcohol dehydrogenase-related loci, from the shape or size of
      the male genital arch, or from assortative premating behavior. We discuss these
      results in relation to a mitochondrial genetic species concept and the potential
      for Wolbachia-induced incompatibility to be a mechanism of speciation in insects.
      We conclude with an iterated appeal to include phylogenetic and statistical tests
      of neutrality as a supplement to phylogenetic and population genetic analyses
      when using mtDNA as an evolutionary marker.

PMID- 11989684
TI  - Flies across the water: genetic differentiation and reproductive isolation in
      allopatric desert Drosophila.
AB  - Between sister species of Drosophila, both pre- and postzygotic reproductive
      isolation commonly appear by the time a Nei's genetic distance of 0.5 is
      observed. The degree of genetic differentiation present when allopatric
      populations of the same Drosophila species exhibit incipient reproductive
      isolation has not been systematically investigated. Here we compare the
      relationship between genetic differentiation and pre- and postzygotic isolation
      among allopatric populations of three cactophilic desert Drosophila: D. mettleri,
      D. nigrospiracula, and D. mojavensis. The range of all three is interrupted by
      the Gulf of California, while two species, D. mettleri and D. mojavensis, have
      additional allopatric populations residing on distant Santa Catalina Island, off
      the coast of southern California. Significant population structure exists within
      all three species, but only for allopatric populations of D. mojavensis is
      significant isolation at the prezygotic level observed. The genetic distances for
      the relevant populations of D. mojavensis were in the range of 0.12, similar to
      that for D. mettleri whose greatest D = 0.11 was unassociated with any form of
      isolation. These observations suggest further investigations of Drosophila
      populations with genetic distances in this range be undertaken to identify any
      potential patterns in the relationship between degree of genetic differentiation
      and the appearance of pre- and/or postzygotic isolation.

PMID- 11989685
TI  - Why do some social insect queens mate with several males? Testing the sex-ratio
      manipulation hypothesis in Lasius niger.
AB  - Although multiple mating most likely increases mortality risk for social insect
      queens and lowers the kin benefits for nonreproductive workers, a significant
      proportion of hymenopteran queens mate with several males. It has been suggested
      that queens may mate multiply as a means to manipulate sex ratios to their
      advantage. Multiple paternity reduces the extreme relatedness value of females
      for workers, selecting for workers to invest more in males. In populations with
      female-biased sex ratios, queens heading such male-producing colonies would
      achieve a higher fitness. We tested this hypothesis in a Swiss and a Swedish
      population of the ant Lasius niger. There was substantial and consistent
      variation in queen mating frequency and colony sex allocation within and among
      populations, but no evidence that workers regulated sex allocation in response to
      queen mating frequency; the investment in females did not differ among paternity
      classes. Moreover, population-mean sex ratios were consistently less female
      biased than expected under worker control and were close to the queen optimum.
      Queens therefore had no incentive to manipulate sex ratios because their fitness
      did not depend on the sex ratio of their colony. Thus, we found no evidence that
      the sex-ratio manipulation theory can explain the evolution and maintenance of
      multiple mating in L. niger.

PMID- 11989686
TI  - Geometric estimates of heritability in biological shape.
AB  - The recently developed geometric morphometrics methods represent an important
      contribution of statistics and geometry to the study of biological shapes. We
      propose simple protocols using shape distances that incorporate geometric
      techniques into linear quantitative genetic models that should provide insights
      into the contribution of genetics to shape variation in organisms. The geometric
      approaches use Procrustes distances in a curved shape space and distances in
      tangent spaces within and among families to estimate shape heritability. We
      illustrate the protocols with an example of wing shape variation in the honeybee,
      Apis mellifera. The heritability of overall shape variation was small, but some
      localized components depicting shape changes on distal wing regions showed medium
      to large heritabilities. The genetic variance-covariance matrix of the geometric
      shape variables was significantly correlated with the phenotypic shape variance
      covariance matrix. A comparison of the results of geometric methods with the
      traditional multivariate analysis of interlandmark distances indicated that even
      with a larger dimensionality, the interlandmark distances were not as rich in
      shape information as the landmark coordinates. Quantitative genetics studies of
      shape should greatly benefit from the application of geometric methods.

PMID- 11989687
TI  - The historical biogeography of two Caribbean butterflies (Lepidoptera:
      Heliconiidae) as inferred from genetic variation at multiple loci.
AB  - Mitochondrial DNA and allozyme variation was examined in populations of two
      Neotropical butterflies, Heliconius charithonia and Dryas iulia. On the mainland,
      both species showed evidence of considerable gene flow over huge distances. The
      island populations, however, revealed significant genetic divergence across some,
      but not all, ocean passages. Despite the phylogenetic relatedness and broadly
      similar ecologies of these two butterflies, their intraspecific biogeography
      clearly differed. Phylogenetic analyses of mitochondrial DNA sequences revealed
      that populations of D. iulia north of St. Vincent are monophyletic and were
      probably derived from South America. By contrast, the Jamaican subspecies of H.
      charithonia rendered West Indian H. charithonia polyphyletic with respect to the
      mainland populations; thus, H. charithonia seems to have colonized the Greater
      Antilles on at least two separate occasions from Central America. Colonization
      velocity does not correlate with subsequent levels of gene flow in either
      species. Even where range expansion seems to have been instantaneous on a
      geological timescale, significant allele frequency differences at allozyme loci
      demonstrate that gene flow is severely curtailed across narrow ocean passages.
      Stochastic extinction, rapid (re)colonization, but low gene flow probably explain
      why, in the same species, some islands support genetically distinct and
      nonexpanding populations, while nearby a single lineage is distributed across
      several islands. Despite the differences, some common biogeographic patterns were
      evident between these butterflies and other West Indian taxa; such congruence
      suggests that intraspecific evolution in the West Indies has been somewhat
      constrained by earth history events, such as changes in sea level.

PMID- 11989688
TI  - Nuptial gifts and the evolution of male body size.
AB  - In many insect systems, males donate nuptial gifts to insure an effective
      copulation or as a form of paternal investment. However, if gift magnitude is
      both body size-limited and positively related to fitness, then the opportunity
      exists for the gift to promote the evolution of large male size. In the striped
      ground cricket, Allonemobius socius, males transfer a body size-limited, somatic
      nuptial gift that is comprised primarily of hemolymph. To address the
      implications of this gift on male size evolution, we quantified the intensity and
      direction of natural (fecundity) and sexual (mating success) selection over
      multiple generations. We found that male size was under strong positive sexual
      selection throughout the breeding season. This pattern of selection was similar
      in successive generations spanning multiple years. Male size was also under
      strong natural selection, with the largest males siring the most offspring.
      However, multivariate selection gradients indicated that gift size, and not male
      size, was the best predictor of female fecundity. In other words, direct
      fecundity selection for larger gifts placed indirect positive selection on male
      body size, supporting the hypothesis that nuptial gifts can influence the
      evolution of male body size in this system. Although female size was also under
      strong selection due to a size related fecundity advantage, it did not exceed
      selection on male size. The implications of these results with regard to the
      maintenance of the female-biased size dimorphic system are discussed.

PMID- 11989689
TI  - Discovery and phylogenetic analysis of a riverine species flock of African
      electric fishes (Mormyridae: Teleostei).
AB  - The evolution of species-specific mate recognition signals is of particular
      interest within speciose monophyletic groups with restricted distributions (known
      as "species flocks"). However, the explosive nature of speciation in these clades
      makes difficult the reconstruction of their phylogenetic history. Here we
      describe a species flock of riverine mormyrid fishes from west-central Africa in
      which electric signals may play a role in the reproductive isolation of sympatric
      species. In our recent field collections, totaling more than 1400 specimens from
      many localities, we recognize 38 forms that are distinct in their morphologies
      and electric organ discharge (EOD) characteristics. Of these 38, only four
      clearly correspond to described species. Here we treat these forms as operational
      taxonomic units (OTUs) in a phylogenetic analysis of cytochrome b sequence data
      from a sample of 86 specimens. We examined support in the molecular data for the
      monophyly of these 38 OTUs considered together, the monophyly of each
      phenotypically delimited OTU considered individually, and for relationships among
      OTUs congruent with those inferred from the distribution of morphological and EOD
      character states. Trees obtained by both maximum-parsimony and maximum-likelihood
      analyses, rooted with sequence data from outgroup taxa, provide evidence for the
      monophyly of these 38 OTUs with respect to other mormyrid fishes. The small
      genetic distances between many distinct forms suggest their recent divergence.
      However, in many instances the cytochrome b tree topology fails to support the
      monophyly of individual OTUs and close relationships between OTUs that are
      similar in morphology and EOD characteristics. In other cases, individuals from
      distinct OTUs share identical or nearly identical haplotypes. Close examination
      of these cases suggests that unnatural OTU definition is not the sole cause of
      this pattern, and we infer an incongruence between the mitochondrial gene tree
      and the organismal phylogeny caused by incomplete mitochondrial lineage sorting
      and/ or introgression across forms. The apparently rapid diversification in this
      clade of riverine electric fishes and the problems associated with recovering a
      meaningful species-level phylogeny from mitochondrial data parallel findings in
      other species flocks. Selection on EOD waveforms as mate recognition signals may
      be involved in the radiation of these fishes. This is the first description of a
      freshwater fish species flock from a riverine, as opposed to a lacustrine,
      environment.

PMID- 11989690
TI  - Adaptive phenotypic plasticity and genetics of larval life histories in two Rana
      temporaria populations.
AB  - Phenotypic plasticity provides means for adapting to environmental
      unpredictability. In terms of accelerated development in the face of pond-drying
      risk, phenotypic plasticity has been demonstrated in many amphibian species, but
      two issues of evolutionary interest remain unexplored. First, the heritable basis
      of plastic responses is poorly established. Second, it is not known whether
      interpopulational differences in capacity to respond to pond-drying risk exist,
      although such differences, when matched with differences in desiccation risk
      would provide strong evidence for local adaptation. We investigated sources of
      within- and among-population variation in plastic responses to simulated pond
      drying risk (three desiccation treatments) in two Rana temporaria populations
      originating from contrasting environments: (1) high desiccation risk with weak
      seasonal time constraint (southern population); and (2) low desiccation risk with
      severe seasonal time constraint (northern population). The larvae originating
      from the environment with high desiccation risk responded adaptively to the fast
      decreasing water treatment by accelerating their development and metamorphosing
      earlier, but this was not the case in the larvae originating from the environment
      with low desiccation risk. In both populations, metamorphic size was smaller in
      the high-desiccation-risk treatment, but the effect was larger in the southern
      population. Significant additive genetic variation in development rate was found
      in the northern and was nearly significant in the southern population, but there
      was no evidence for genetic variation in plasticity for development rates in
      either of the populations. No genetic variation for plasticity was found either
      in size at metamorphosis or growth rate. All metamorphic traits were heritable,
      and additive genetic variances were generally somewhat higher in the southern
      population, although significantly so in only one trait. Dominance variances were
      also significant in three of four traits, but the populations did not differ.
      Maternal effects in metamorphic traits were generally weak in both populations.
      Within-environment phenotypic correlations between larval period and metamorphic
      size were positive and genetic correlations negative in both populations. These
      results suggest that adaptive phenotypic plasticity is not a species-specific
      fixed trait, but evolution of interpopulational differences in plastic responses
      are possible, although heritability of plasticity appears to be low. The lack of
      adaptive response to desiccation risk in northern larvae is consistent with the
      interpretation that selection imposed by shorter growing season has favored rapid
      development in north (approximately 8% faster development in north as compared to
      south) or a minimum metamorphic size at the expense of phenotypic plasticity.

PMID- 11989691
TI  - The effect of miniaturized body size on skeletal morphology in frogs.
AB  - Miniaturization has evolved numerous times and reached impressive extremes in the
      Anura. I compared the skeletons of miniature frog species to those of closely
      related larger species to assess patterns of morphological change, sampling 129
      species from 12 families. Two types of morphological data were examined: (1)
      qualitative data on bone presence and absence; and (2) thin-plate spline
      morphometric descriptions of skull structure and bone shape. Phylogenetic
      comparative methods were used to address the shared history of species. Miniature
      anurans were more likely to lose skull bones and phalangeal elements of the
      limbs. Their skulls also showed consistent differences compared to those of their
      larger relatives, including relatively larger braincases and sensory capsules,
      verticalization of lateral elements, rostral displacement of the jaw joint, and
      reduction of some skull elements. These features are explained by functional
      constraints and by paedomorphosis. Variation among lineages in the morphological
      response to miniaturization was also explored. Certain lineages appear to be
      unusually resistant to the morphological trends that characterize miniature frogs
      as a whole. This study represents the first large-scale examination of morphology
      and miniaturization across a major, diverse group of organisms conducted in a
      phylogenetic framework and with statistical rigor.

PMID- 11989692
TI  - An epistatic genetic basis for fluctuating asymmetry of mandible size in mice.
AB  - The genetic basis of fluctuating asymmetry (FA), or nondirectional variation in
      the subtle differences between left and right sides of bilateral characters,
      continues to be of considerable theoretical interest. FA generally has been
      thought to arise from random noise during development and therefore to have a
      largely or entirely environmental origin. Whereas additive genetic variation for
      FA generally has been small and often insignificant, a number of investigators
      have hypothesized that interactions between loci, or epistasis, significantly
      influence FA. We tested this hypothesis by conducting a whole-genome scan to
      detect any epistasis in FA of centroid size in the mandibles of more than 400
      mice from an F2 intercross population formed from crossing the Large (LG/J) and
      Small (SM/J) inbred strains. Genotypic deviations were imputed at each site 2 cM
      apart on all 19 autosomes, and these and centroid size asymmetry values were used
      in canonical correlation analyses for each of the 171 possible pairs of 19
      autosomes to identify the most probable sites for epistasis. Epistasis for
      centroid size asymmetry was abundant, occurring far more often than was expected
      by chance alone (there were 30 separate instances of epistasis at the 0.001
      significance level, when only two were expected by chance alone). The
      contributions of epistasis from 30 pairwise combinations of loci tended to
      suppress the additive and dominance genetic variance, but greatly increased the
      epistatic genetic variance for FA in centroid size given the intermediate allele
      frequencies of an F2 intercross population.

PMID- 11989693
TI  - Lethals in finite populations.
AB  - It has been assumed, based on theoretical studies, that lethals with the level of
      dominance estimated from experimental studies would have an allele frequency that
      is virtually independent of effective population size. However, here it is shown
      numerically that the expected frequency of lethals with low levels of dominance
      is also dependent on finite population size, although not as much as completely
      recessive lethals. This finding is significant in determining the standing level
      of inbreeding depression and the consequent potential for the evolution of self
      fertilization. In addition, the architecture of genetic variation influencing
      inbreeding depression in populations with a history of small size may be of
      important consequence in endangered species. Finally, it is shown that the loss
      of lethal genetic variation often occurs much more quickly than the regeneration
      of lethal variation by mutation. This asymmetry may result in a lower standing
      genetic variation for inbreeding depression than expected from mutation rates and
      contemporary population size data.

PMID- 11989694
TI  - Synthetic aperture imaging with arrays of arbitrary shape--part I: General case.
AB  - The problem of synthesizing full-aperture resolution with linear transmitting and
      receiving arrays of arbitrary shape is considered. The arrays are assumed to lie
      in the same plane and can be open (e.g., curved or straight line segments) or
      closed (e.g., circles). It is shown that a full (area) aperture can be
      synthesized by suitably weighting the transmitted and received signals. This
      weighting turns out to be the Jacobian of a transformation that yields uniform
      coverage in the spatial-frequency domain. If the Jacobian is factorable, then
      full-aperture resolution can be achieved in a single transmission. The theory is
      illustrated with two annular arrays of different diameter: one that transmits and
      one that receives. If the radii of the annular arrays are a and b, then the
      synthesized point-spread function (PSF) is shown to be equivalent to that of a
      filled circular aperture of radius a + b.

PMID- 11989695
TI  - Synthetic aperture imaging with arrays of arbitrary shape--part II: The annular
      array.
AB  - It has been previously shown that full aperture resolution can be achieved with
      an annular transducer array by transmitting and receiving between all pairs of
      elements around the array circumference and applying an appropriate weighting
      function. If there are N elements in the array, this requires N transmissions.
      This paper shows that full aperture resolution can be obtained with a much
      smaller number of transmissions (two to four) by using a certain aperture phase
      weighting on transmit and receive. Thus, full aperture, real-time imaging from an
      annular array should be feasible.

PMID- 11989696
TI  - Supercritical parametric wave phase conjugation as an instrument for narrowband
      analysis in ultrasonic harmonic imaging.
AB  - Supercritical parametric wave phase conjugation (SWPC) is used for selection and
      phase conjugation of harmonic components of a nonlinear incident wave. Amplitude
      of the phase conjugate wave in a supercritical mode is high enough for acoustic
      nonlinearity of propagation medium to appear. As a result, in particular, doubled
      and quadrupled frequencies of the incident wave become available for image
      formation at the same order of the medium nonlinearity. The improvement of the
      imaging system resolution because of harmonic analysis of the received acoustic
      signal and compensation of phase distortions caused by wave phase conjugation
      were observed simultaneously when propagation medium was inhomogeneous.

PMID- 11989697
TI  - Intracardiac catheter 2-D arrays on a silicon substrate.
AB  - The design, fabrication, and characterization of a 7 MHz, two-dimensional (2-D)
      array transducer built on a silicon substrate is described. The array fits inside
      a 9-French (2.9 mm O.D.) catheter for use in real-time intracardiac volumetric
      imaging. The -6 dB fractional bandwidth of the transducer is 30%, the 50 ohm
      pitch-catch insertion loss is 78 dB, and the interelement crosstalk is -25 dB.
      Real-time volumetric images in phantoms and in-vitro images of a sheep heart have
      been acquired yielding measured spatial resolution of 2 mm at a depth of 1 cm.
      The cardiac structures imaged include ventricular chambers, interventricular
      septum, mitral and tricuspid valves and real-time 3-D rendered volumes of the
      tricuspid valve in the open and closed position.

PMID- 11989698
TI  - Shear modulus imaging with 2-D transient elastography.
AB  - In previous works, we have shown that time-resolved 2-D transient elastography is
      a promising technique for characterizing the elasticity of soft tissues. It
      involves the measurement of the displacements induced by the propagation of low
      frequency (LF) pulsed shear waves in biological tissues. In this paper, we
      present a novel apparatus that contains a LF vibrating device surrounding a
      linear array of 128 ultrasonic transducers that performs ultrafast ultrasonic
      imaging (up to 10,000 frames/s) and that is able to follow in real time the
      propagation of a LF shear wave in the human body. The vibrating device is made of
      two rods, fixed to electromagnetic vibrators, that produce in the ultrasonic
      image area a large amplitude shear wave. The geometry has been chosen both to
      enhance the sensitivity and to create a quasi linear shear wave front in the
      imaging plane. An inversion algorithm is used to recover the shear modulus map
      from the spatio-temporal data, and the first experimental results obtained from
      tissue-equivalent materials are presented.

PMID- 11989699
TI  - Shear elasticity probe for soft tissues with 1-D transient elastography.
AB  - Important tissue parameters such as elasticity can be deduced from the study of
      the propagation of low frequency shear waves. A new method for measuring the
      shear velocity in soft tissues is presented in this paper. Unlike conventional
      transient elastography, in which the ultrasonic transducer and the low frequency
      vibrator are two separated parts, the new method relies on a probe that
      associates the vibrator and the transducer, which is built on the axis of the
      vibrator. This setup is easy to use. The low frequency shear wave is driven by
      the transducer itself that acts as a piston while it is used in pulse echo mode
      to acquire ultrasonic lines. The results obtained with the new method are in good
      agreement with those obtained with the conventional one.

PMID- 11989700
TI  - Micro-receiver guided transcranial beam steering.
AB  - A new method for focusing ultrasound energy in brain tissue through the skull is
      investigated. The procedure is designed for use with a therapeutic transducer
      array and a small catheter-inserted hydrophone receiver placed in the brain to
      guide the array's focus. When performed at high-intensity, a focal intensity on
      the order of several hundred watts per centimeter-squared is achieved, and cells
      within a target volume are destroyed. The present study tests the feasibility and
      range of the method using an ex vivo human skull. Acoustic phase information is
      obtained from the stationary receiver and used to electrically shift the beam to
      new locations as well as correct for aberrations due to the skull. The method is
      applied to a 104-element 1.1 MHz array and a 120-element 0.81 MHz array. Using
      these array configurations, it is determined that the method can reconstruct and
      steer a focus over a distance of 50 mm. Application of this minimally invasive
      technique for ultrasound brain therapy and surgery also is investigated in vitro
      with a 64-element 0.664 MHz hemisphere array designed for transskull surgery.
      Tissue is placed inside of a skull and a catheter-inserted receiver is inserted
      into the tissue. A focus intense enough to coagulate the tissue is achieved at a
      predetermined location 10 mm from the receiver, the maximum distance that this
      large element array can electronically steer the focus.

PMID- 11989701
TI  - Standardized evaluation of chemical compositions of LiTaO3 single crystals for
      SAW devices using the LFB ultrasonic material characterization system.
AB  - The line-focus-beam ultrasonic material characterization (LFB-UMC) system is
      applied to compare and evaluate tolerances provided independently for the Curie
      temperature T(C) and lattice constant a to evaluate commercial LiTaO3 single
      crystals by measuring the Rayleigh-type leaky surface acoustic wave (LSAW)
      velocities V(LSAW). The relationships between V(LSAW), and T(C) and a measured by
      individual manufacturers were obtained experimentally using 42 degrees Y X-LiTaO3
      wafers as specimens from three crystal manufacturers. In addition, the
      relationship between V(LSAW) and SH-type SAW velocities V(SAW) that are actually
      used for the SAW device wafers was obtained through calculations, using the
      chemical composition dependences of the acoustical physical constants for LiTaO3
      crystals reported previously. The result of a comparison between the T(C)
      tolerance of +/-3 degrees C and the a tolerance of +/-0.00002 nm through the
      common scale of V(LSAW) or V(SAW) demonstrated that the a tolerance is 1.6 times
      larger than the T(C) tolerance. Furthermore, we performed a standardized
      comparison of statistical data of T(C) and a for LiTaO3 crystals grown by two
      manufacturers during 1999 and 2000, using V(LSAW). The results clarified the
      differences of the average chemical compositions and of the chemical composition
      distributions among the crystal ingots between the two manufacturers. A guideline
      for the standardized evaluation procedure has been established for the SAW-device
      wafer specifications by the LFB-UMC system.

PMID- 11989702
TI  - Design on semiconductor coupled SAW convolver.
AB  - This paper presents results of a design study on a semiconductor coupled surface
      acoustic wave (SAW) convolver in which bi-directionally propagating SAWs, on a
      piezoelectric substrate with a high coupling coefficient, couple with bonded
      semiconductor diodes through multistrips. To obtain convolution signals with a
      high efficiency, we adopted a diode-balanced bridge structure for the non-linear
      operation. We also found that the tapping pitches of the multi-strip electrodes
      have robustness against operation frequency variation and temperature-dependent
      variation on the delay of the SAW. We verified the effectiveness of the device in
      a circuit simulation and an experiment on a test circuit, which was fabricated by
      using an epitaxial lift-off film-bonding process.

PMID- 11989703
TI  - The influence of fabrication errors on the stopband magnitude responses of SAW
      devices.
AB  - This article is devoted to the analysis of the influence of manufacturing errors
      on the magnitude responses of surface acoustic wave (SAW) devices. Analytical
      analysis of these random errors provides statistical distributions of the
      relevant responses and their parameters. It allows significant reduction in the
      modeling computations compared to the Monte Carlo method, and it provides
      possibilities for further analytical analysis. After the application of the
      statistical analysis to different potential structures of SAW devices, it is
      possible to choose the least sensitive one during the design process without the
      need of costly trials. Experimental analysis confirmed the existence of some of
      the features predicted both theoretically and by modeling. The experimental
      procedure for the evaluation of the fabrication error variances is described. The
      application of these results to the design process of the SAW devices allows
      simplification of the requirements for the manufacturing equipment and/or
      improvement of the devices' parameters, especially stopband suppression.

PMID- 11989704
TI  - Efficiency of excitation of piezoceramic transducers at antiresonance frequency.
AB  - The efficiency of piezoceramic transducers excited at both the resonance and
      antiresonance frequency was investigated. Losses in piezoceramics are
      phenomenologically considered to have three coupled mechanisms: dielectric,
      mechanical, and piezoelectric losses. Expressions for the resonance and
      antiresonance quality factors, which ultimately determine transducer efficiency,
      have been received on the basis of complex material constants for both stiffened
      and unstiffened vibration modes. Comparison of electric and mechanical fields,
      thermal and electrical losses of power supply, and their distribution in the
      transducer volume have been made. For a given constant mechanical displacement of
      the transducer top, the required electric voltage applied to the transducer at
      the antiresonance frequency is proportional to the resonance quality factor, but
      the changes in the intrinsic electric and mechanical field characteristics in the
      common case are not too essential. The requirements on the piezoceramic
      parameters, types of transducer vibration, and especially on the factor of
      piezoelectric losses in a range of physically valid values were established to
      provide maximal quality factors at the antiresonance frequency.

PMID- 11989705
TI  - A piezoelectric motor using two orthogonal bending modes of a hollow cylinder.
AB  - This paper proposes a compact ultrasonic motor with low manufacturing costs, a
      simpler driving circuit, and scalability. The stator of the motor presented in
      this paper consists of a hollow metal cylinder, whose outside surface was
      flattened on two sides at 90 degrees to each other, on which two rectangular
      piezoelectric plates were bonded. Because the cylinder has a partially
      square/partially circular outside surface, the stator has two degenerated bending
      modes that are orthogonal to each other. A wobbling motion is generated on the
      cylinder when only one piezoelectric plate is excited at a frequency between the
      two orthogonal bending modes. A rod through a pair of ferrules was used as the
      rotor of this motor. The prototype motor, whose stator was 2.4 mm in diameter and
      10 mm in length, operated at 69.5 kHz, was experimentally characterized, and a
      maximum torque of 1.8 mNm was obtained.

PMID- 11989706
TI  - A low-flicker scheme for the real-time measurement of phase noise.
AB  - This paper presents a new scheme for the measurement of phase noise in real time,
      based on carrier suppression and synchronous detection of the noise sidebands of
      the device being tested. In the instruments of the interferometric type, the
      carrier is suppressed by adding an equal and opposite signal that must be
      adjusted with a phase shifter and an attenuator. The proposed scheme makes use of
      a dual adjustment of the carrier suppression, coarse and fine. The former is by
      step; the latter is continuous. Because of the higher stability of the by-step
      adjustment and the lower weight of the continuous adjustment in the suppression
      circuit, the instrument exhibits intrinsically low residual flicker and low
      microphonicity. A prototype shows a residual flicker as low as -160 dBrad2/Hz at
      1 Hz off the 100 MHz carrier. Applications include the noise characterization of
      components and the design of innovative ultrastable oscillators.

PMID- 11989707
TI  - Application of the moment condition to noise simulation and to stability
      analysis.
AB  - It is well-known that low frequency noises (flicker FM and random walk FM) are
      not stationary; it is not possible to define either the mean value or the (true)
      variance. Therefore, the use of a stationary approach yields convergence problems
      unless a low cut-off frequency is introduced, the physical meaning of which is
      not clear. As an example, in the case of random walk FM, the mean frequency of an
      oscillator does not converge if the analysis duration tends toward infinity.
      However, linear drifts appear if a phase sequence of random walk FM is observed
      over a duration smaller than the inverse of its low cut-off frequency. Moreover,
      the estimators, which are devoted to these non-stationary processes (i.e., the
      Hadamard variance), are insensitive to linear frequency drifts and converge for
      lower frequency noises (f(-4) FM). The moment condition explains the link between
      insensitivity to drifts and convergence for low frequency noises in a stationary
      approach. This condition may be summarized by the following consideration: the
      divergence effect of a low frequency noise for the lowest frequencies induces a
      false drift with random drift coefficients; the lower the low cut-off frequency,
      the higher the variance of the coefficients of this drift. These variances may be
      known by theoretical calculations. The order of the drift is directly linked to
      the power law of the noise. The moment condition will be demonstrated and applied
      for creating new estimators (new variances) and for simulating low frequency
      noises with a very low cut-off frequency.

PMID- 11989708
TI  - Isochronism defect for various doubly rotated cut quartz resonators.
AB  - It has been shown in earlier works that the amplitude-frequency effect [also
      called isochronism defect (ID) or anisochronism] could be a limitation factor on
      ultrastable oscillators. Theoretical studies based on the nonlinear theory of
      piezoelectricity have already been developed to explain the amplitude-frequency
      effect. So, it is possible to estimate the dependence of the ID versus various
      parameters of the resonator design (overtone rank, radius of curvature,
      electrodes diameter, etc.). However, because of the lack of available fourth
      order elastic coefficients, it is not possible to predict the ID of any resonant
      frequency of a given trapped energy resonator. To tentatively find orientations
      of plates exhibiting a quasi-null ID, we have realized electroded resonators with
      different orientations and curvatures. We present results that verify,
      particularly, the R(-1/2) dependence of the amplitude-frequency effect versus
      radius of curvature. Moreover, we show that the ID can be positive or negative,
      that it can vary from one orientation to other one of about one order of
      magnitude, and that there exists a thermal compensated mode for which the
      amplitude-frequency effect is null.

PMID- 11989709
TI  - Analysis of general multi-channel planar waveguides.
AB  - Using the planar waveguide concept in surface acoustic wave (SAW) technology is
      often advantageous when the modeling of transversely distributed phenomena is
      indispensable for an accurate design of SAW devices. This is especially true when
      complex multi-track structures such as transversely coupled resonator filters
      (TCRFs) are under consideration where, e.g., transverse velocity and stiffness
      profiles have to be incorporated in the device simulation. The interdigital
      transducers (IDTs) and the reflector gratings composing those devices behave as
      planar waveguides, supporting, in principle, all kinds of modes such as bound,
      semi-bound, and radiation modes. Therefore, to model these SAW propagation
      effects, we subdivide the SAW structures in transverse direction into several
      parallel waveguiding channels (N regions), and take, as the wave-describing
      quantity, a two-dimensional scalar potential function. By doing so, we obtain a
      complete set of orthonormal modes into which an arbitrary transverse excitation
      function can be expanded to study its propagation. The general mode spectrum
      includes a discrete spectrum of bound modes and continuous spectra of semi-bound
      and radiation modes. We calculate all types of modes by making use of the stack
      matrix technique. The present work, which arose from the requirement of creating
      an efficient mathematical tool for the simulation of TCRFs, provides the complete
      analysis of general SAW multi-channel structures.

PMID- 11989710
TI  - Harmonic admittance and dispersion equations--the theorem.
AB  - The harmonic admittance is known as a powerful tool for analyzing the excitation
      and propagation of surface acoustic waves (SAWs) in periodic electrode arrays. In
      particular, the dispersion relationships for open- and short-circuited systems
      are indicated, respectively, by the zeros and poles of the harmonic admittance.
      Here, we show that a strict reverse relationship also exists: the harmonic
      admittance of a periodic system of electrodes may always be expressed as the
      ratio of two determinants, which have been specifically constructed to describe
      the eigen-modes of the open- and short-circuited systems. There is no need to
      solve these equations to find the admittance. The existence of a connection
      between the excitation and propagation problems was recognized within the
      coupling-of-modes theory by Chen and Haus and was recently used to model surface
      transverse waves by Koskela et al., but a rigorous mathematical proof was only
      found later by Biryukov. Here, we reproduce this theorem in detail, give some
      examples of calculations based on this theorem, and compare the results with
      measured admittance curves.

PMID- 11989711
TI  - Thin film bulk acoustic wave filter.
AB  - Thin film bulk acoustic wave (BAW) resonators (FBAR) are fabricated on a silicon
      nitride bridge using a ZnO piezolayer on a glass substrate and surface
      micromachining by standard thin film technology. These resonators exhibit a
      coupling constant k(t)2 = 7.8% at the first thickness extensional wave mode and
      are used as impedance elements in a ladder filter in the 1-GHz frequency band of
      mobile telecommunications. An electrical equivalent circuit is used to
      characterize the properties of the resonators and to show how the performance of
      the filter depends on the parameters of the resonators. 2.5% bandwidth, 2.8-dB
      insertion loss, and 35-dB selectivity are obtained in a filter with six
      resonators. The technology can be used to manufacture miniature microwave filters
      without any additional inductances.

PMID- 11989712
TI  - Gene for integrin-associated protein (IAP, CD47): physical mapping, genomic
      structure, and expression studies in skeletal muscle.
AB  - Integrin-associated protein (IAP) is a widely expressed membrane protein with
      multiple functions in immunological and neuronal processes. Having physically
      mapped the IAP gene into a BAC/PAC contig covering approximately 1 Mb on human
      chromosome 3ql3.1-q13.2, we determined the genomic organization of the gene,
      established its expression in skeletal muscle, and identified a novel splice
      variant. Our expression studies demonstrate expression of integrin-associated
      protein in the t-tubular system and the euchromatin of skeletal muscle cells
      where its function thus far is not known.

PMID- 11989713
TI  - Minimal promoter for the NAD+-specific glutamate dehydrogenase gene of Neurospora
      crassa.
AB  - The expression of the NAD+-specific glutamate dehydrogenase (NAD-GDH) gene of
      Neurospora crassa is subject to catabolite repression. To identify the minimal
      sequence necessary for promoter function, the 5'-flanking region of the NAD-GDH
      gene was screened for potential protein-binding sites. Fragments of DNA,
      containing sequences upstream from the ATG initiation codon, were employed as
      probes of Southwestern blots of total cellular protein from cells grown in media
      promoting repression and induction of NAD-GDH. Two polypeptides interacted
      differentially with a promoter probe; one was present in greater abundance in
      repressed cells and a higher relative level of the second was witnessed in
      induced cells. Electrophoretic mobility shift assays with labeled promoter
      fragments exhibited preferential interaction with proteins in the induced
      cultures. The upstream sequence containing the putative protein-binding sites was
      fused with the coding sequence of the green fluorescent protein (GFP). The
      resulting plasmid was introduced into the microconidia of an albino mutant of N.
      crassa by electroporation. Stable integration of the plasmid and_expression of
      GFP in the hyphae and conidia of the transformants were demonstrated by Southern
      and Western blot analysis and fluorescence microscopy.

PMID- 11989714
TI  - Production and characterization of an in vitro engineered human oral mucosa.
AB  - The role of epithelial cells in oral pathologies is poorly understood. Until now,
      most studies have used normal or transformed epithelial cell monolayers, a system
      that largely bypasses oral mucosal complexity. To overcome these limitations, an
      engineered human oral mucosa (EHOM) model has been produced and characterized.
      Following histological and immunohistochemical analyses, EHOM showed well
      organized and stratified tissues in which epithelial cells expressed
      proliferating keratins such as Ki-67, K14, and K19 and also differentiating
      keratin (K10). In this model, epithelial cells interacted with fibroblasts in the
      lamina propria by secreting basement membrane proteins (laminins) and by
      expressing integrins (beta1 and alpha2beta1). Cytokine analyses using cultured
      supernatants showed that cells in EHOM were able to secrete interleukins (IL)
      including IL-1beta and IL-8 and tumor necrosis factor alpha (TNF-alpha). Finally,
      cells in this engineered model were able to secrete different metalloproteinases
      such as gelatinase-A and gelatinase-B. In conclusion, using tissue engineering
      technology, we produced well-organized EHOM tissues. It is anticipated that this
      model will be useful for examining mechanisms involved in oral diseases under
      controlled conditions by modeling the interactions between mucosa and
      microorganisms in the oral cavity.

PMID- 11989715
TI  - Probing electrostatic interactions in cytochrome c using site-directed chemical
      modification.
AB  - This communication reports the generation of an electrostatic probe using
      chemical modification of methionine side chains. The alkylation of methionine by
      iodoacetamide was achieved in a set of Saccharomyces cerevisiae iso-1-cytochrome
      c mutants, introducing the nontitratable, nondelocalized positive charge of a
      carboxyamidomethylmethionine sulfonium (CAMMS) ion at five surface and one buried
      site in the protein. Changes in redox potential and its variation with
      temperature were used to calculate microscopic effective dielectric constants
      operating between the probe and the heme iron. Dielectric constants (epsilon)
      derived from deltadeltaG values were not useful due to entropic effects, but
      epsilon(deltadeltaH) gave results that supported the theory. The effect on
      biological activity of surface derivatization was interpreted in terms of protein
      protein interactions. The introduction of an electrostatic probe in cytochrome c
      often resulted in marked effects on activity with one of two physiological
      partners: cytochrome c reductase, especially if introduced at position 65, and
      cytochrome c oxidase, if at position 28.

PMID- 11989716
TI  - Activity and conformational changes of horseradish peroxidase in
      trifluoroethanol.
AB  - The effect of trifluoroethanol (TFE) on horseradish peroxidase (HRP) was
      determined using activity assay and spectral analysis including optical
      absorption, circular dichroism (CD), and intrinsic fluorescence. The enzyme
      activity increased nearly twofold after incubation with 5-25% (v/v)
      concentrations of TFE. At these TFE concentrations, the tertiary structure of the
      protein changed little, while small changes occurred at the active site. Further
      increases in the TFE concentration (25-40%) decreased the enzyme activity until
      at 40% TFE the enzyme was completely inactivated. The alpha-helix content of the
      protein increased at high TFE concentrations, while near-UV CD, Soret CD, and
      intrinsic fluorescence indicated that the tertiary structure was destroyed.
      Polyacrylamide gel electrophoresis results indicated that the surface charge of
      the enzyme was changed at TFE concentrations greater than 20%, and increasing
      concentrations of TFE reduced the enzyme molecular compactness. A scheme for the
      unfolding of HRP in TFE was suggested based on these results. The kinetics of
      absorption change at 403 nm in 40% TFE followed a two-phase course. Finally, HRP
      incubated with TFE was more sensitive to urea denaturation, which suggested that
      the main effect of TFE on HRP was the disruption of hydrophobic interactions.

PMID- 11989717
TI  - Purification, physicochemical properties, and subcellular location of alkaline
      inorganic pyrophosphatase from sesame (Sesamum indicum L.) cotyledons.
AB  - Abstract: Changes in the levels of inorganic pyrophosphatases (PPases) were
      monitored in germinating sesame seeds at regular intervals. Activities of acid
      and alkaline PPases increased markedly in cotyledons up to day 4, remained at the
      peak level up to day 7, and then showed a considerable decline thereafter. An
      alkaline PPase was isolated and purified from 5-day-old sesame cotyledons
      following acetone precipitation, ammonium sulfate fractionation, and
      chromatography on DEAE-Sephadex. Current protocol yielded about 20% recovery of
      total activity with a 6.4-fold purification. The enzyme was a monomer with a
      molecular mass of 20.8 kDa. Some of the properties of alkaline PPase including
      stability, substrate specificity, ion requirement, and amino acid composition
      were studied. Alkaline PPase showed maximum activity at pH 8.6 in the presence of
      Mg2+ and at 50 degrees C. However, the metal ion could not protect the enzyme
      against thermal denaturation. Alkaline PPase was highly specific for inorganic
      pyrophoaphate (PP) as substrate and the Km value was 0.7677 +/- 0.0528 mM. Full
      activation of the enzyme was achieved with a Mg2+/PPi ratio of 2. Divalent metal
      ions such as Ca2+, Cu2+, and Zn2+ inhibited PPase activity. Mg2+, partially
      relieved the inhibition caused by adenosine 5'-triphosphate. Studies related to
      the localization of alkaline PPase in microbodies revealed that the enzyme was
      distributed between glyoxysomes and mitochondria, with the former containing more
      of it.

PMID- 11989718
TI  - Comparative modeling of the phosphatase and kinase domains of protein tyrosine
      phosphatase and insulin receptor kinase from Drosophila melanogaster (DPTP61fm),
      and a computational study of their mutual interactions.
AB  - The components and functions of the insulin receptor kinase signaling pathway
      have been conserved in a broad range of Metazoa ranging from mammals to insects
      and nematodes. There is a high degree of sequence homology and functional
      similarity between the human insulin receptor kinase (IRK) and the drosophila
      (Drosophila melanogaster) form (DIRK) of this enzyme. Similarly, a high degree of
      homology exists between human protein tyrosine phosphatase 1B (PTP1B) (which
      directly regulates IRK) and its drosophila counterpart DPTP61F (DPTP). However,
      genetic and biochemical studies have yet to demonstrate that DPTP61F acts in the
      DIRK pathway. Comparative structural modeling techniques using the known
      structures of human IRK and PTP1B as templates have yielded structures for the
      drosophila enzymes. The derived structures confirm that there is a high level of
      structural conservation at the tertiary level. Association of the DIRK and DPTP
      enzymes with each other was then investigated with a view to ascertaining whether
      DIRK might be a substrate of the DPTP. Evaluation of the interaction surfaces,
      including hydrophobic patch, shape, hydrogen bonding, and electrostatic
      compatibility, strongly suggested that the drosophila insulin receptor is a
      substrate of the DPTP. The interaction surfaces of the human and drosophila
      enzymes are structurally similar, although changes in critical residues modify
      possible electrostatic and hydrogen-bonding interactions. This suggests that in
      the mixed systems, DPTP-IRK or PTP1B-DIRK, the kinase domain will be a
      comparatively poor substrate for phosphatase activity when compared with the
      native systems.

PMID- 11989719
TI  - Phosphorylation decreases trypsin activation and apolipoprotein al binding to
      glycosylphosphatidylinositol-specific phospholipase D.
AB  - Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is present in
      plasma as an apolipoprotein and as a cell-associated lipase. GPI-PLD mRNA levels
      are regulated, but it is unclear if posttranslational mechanisms also regulate
      GPI-PLD function. We examined the effect of protein kinase A phosphorylation on
      human serum GPI-PLD activity, trypsin activation, and apolipoprotein AI binding.
      Protein kinase A phosphorylation did not activate GPI-PLD activity in vitro, nor
      did phosphorylated GPI-PLD cleave a GPI-anchored protein from intact porcine
      erythrocytes. Trypsin cleaves the C-terminal beta propeller of purified human
      serum GPI-PLD to generate three immunodetectable fragments (75, 28, and 18 kDa)
      in association with a 12-fold increase in enzyme activity. After phosphorylation,
      the amounts of 28- and 18-kDa fragments were markedly decreased with trypsin
      treatment, and activity was only increased five-fold. Phosphorylation also
      inhibits binding of GPI-PLD to apolipoprotein AI. These data are the first
      demonstrating that phosphorylation may regulate GPI-PLD interaction with other
      proteins.

PMID- 11989720
TI  - Synthesis of ribosomal proteins in developing Dictyostelium discoideum cells is
      controlled by the methylation of proteins S24 and S31.
AB  - Ribosomal protein mRNAs left over from growth are selectively excluded from
      polyribosomes in the first half of Dictyostelium discoideum development. This is
      due to the fact that they are sequestered by a class of free 40S ribosomal
      subunits, characterized by possessing a methylated S24 protein. At the time of
      formation of tight cell aggregates, the methylated S24 is substituted by an
      unmethylated S24, while protein S31 of the same or other 40S subunits becomes
      methylated. This leads to a rapid degradation of the ribosomal protein mRNAs.

PMID- 11989721
TI  - Gene expression of immunomodulatory cytokines induced by Narcissus tazetta lectin
      in the mouse.
AB  - The immunomodulation of Narcissus tazetta lectin (NTL) on the induction of gene
      expression of cytokines in the mouse was studied using specific cytokine primers,
      total RNA isolated from mouse splenocytes and macrophages, and reverse
      transcription-polymerase chain reaction (RT-PCR). For comparison, a fungal
      antimitogenic lectin from Agaricus bisporus (ABL) was used to test and compare
      the acute (kinetic) induction of cytokine gene expression. NTL was able to induce
      the expression of IL-1beta, TNF-alpha, and immunoreactive nitric oxide synthase
      (NOS) in both splenocytes and macrophages in vivo after 10-day consecutive
      peritoneal injections of 5 mg NTL x kg(-1) x day(-1) in the mouse. Nevertheless,
      the expression levels of IFN-gamma and TGF-beta were markedly increased in
      macrophages, and the levels of IL-2 and IL-4 were up-regulated only in
      splenocytes. From the kinetic pattern of cytokine induction and gene expression,
      ABL appeared to induce the up-regulation of IL-1beta and TNF-alpha in splenocytes
      up to 24 h, whereas NTL showed a more sustained effect on the expression of these
      cytokines in macrophages. While NTL manifested TGF-beta expression at the onset
      of 12 and 24 h in macrophages and splenocytes, respectively, ABL induced TGF-beta
      in neither splenocytes nor macrophages. After injection of NTL, stem-cell factor
      was clearly down-regulated in macrophages at 24 and 48 h but up-regulated in
      splenocytes at the end of 24 h. The immunopotentiating effect of NTL is quite
      similar to that of LZ-8, a fungal immunomodulatory lectin isolated from the
      Chinese premier medicinal mushroom Ganoderma lucidium. However, the mechanism of
      immunomodulation of NTL still awaits to be elucidated.

PMID- 11989722
TI  - Speed and capacity of language processing test: normative data from an older
      American community-dwelling sample.
AB  - This study presents normative data for the Speed and Capacity of Language
      Processing (SCOLP) testfrom an older American sample. The SCOLP comprises 2
      subtests: Spot-the-Word, a lexical decision task, providing an estimate of
      premorbid intelligence, and Speed of Comprehension, providing a measure of
      information processing speed. Slowed performance may resultfrom normal aging,
      brain damage (e.g., head injury), or dementing disorders or may represent the
      intact performance of someone who always performed at the low end of normal. The
      SCOLP enables the clinician to differentiate between these possibilities.
      Adequate age-appropriate norms to differentiate dementia from normal aging do not
      exist. We present data from 424 older community-dwelling Americans (75-94 years
      old). The results confirm that information processing speed slows with increasing
      age. By contrast, increasing age has little effect on lexical decision. Thus, our
      data suggest that the SCOLP shows promise as a tool to help distinguish between
      normal aging and the early stages of dementia.

PMID- 11989723
TI  - Subjective complaints, verbal fluency, and working memory in mild multiple
      sclerosis.
AB  - Patients with mild multiple sclerosis (MS) regularly report subjective complaints
      characterized by generalized cognitive inefficiency. A feature of these
      complaints is reduced verbal fluency, for example, losing the thread of
      conversation. Mild MS patients and controls were compared on subjective
      complaints, verbal fluency, and working memory, and the possible role of working
      memory was investigated. As predicted, subjective difficulties and verbalfluency
      each correlated with working memory. Subjective difficulties and verbal fluency
      were also related. Within the control group, the subjective difficulties were
      associated only with depression. On the other hand, in the MS group, subjective
      difficulties were unrelated to affective state but were correlated with working
      memory. For the patients, partialing out depression and anxiety did not influence
      any of the correlations involving subjective difficulties, verbal fluency, or
      working memory. These findings support the proposal that working memory
      impairment underlies subjective complaints of mild MS patients and that verbal
      dysfluency is part and parcel of this phenomenon.

PMID- 11989724
TI  - Dementia severity and pattern of cognitive performance in vascular dementia.
AB  - We evaluated the influence of dementia severity on cognitive performance in two
      groups of individuals with vascular dementia (VaD). Performance on the Mini
      Mental State Exam (MMSE) was used to determine dementia severity. Tests of
      executive function, psychomotor speed, memory, language, and visuospatial
      function were administered. As expected, individuals with severe VaD (MMSE < 18)
      performed significantly more poorly than individuals with mild VaD (MMSE > or =
      18) on most tests. More important, deficits were evident for both groups in each
      cognitive domain when compared to normative data. These results indicate that
      multiple cognitive domains are affected even in mild cases of VaD. Clinicians
      should be aware that although the presence of "patchy" cognitive deficits may
      indicate stroke, general cognitive dysfunction may occur in mild cases of VaD.

PMID- 11989725
TI  - Evaluation of practice effects in language and spatial processing test
      performance.
AB  - Recent research demonstrates that practice effects are attenuated through the
      administration of alternate-form memory tests. However, little is known about the
      degree of practice that can be expected when alternate forms of nonmemory tests
      are administered repeatedly. Two groups of healthy older adults were assigned to
      either a same- or alternate-forms condition. Participants completing the same
      forms of a confrontation naming task improved significantly over 4 testing
      sessions. On verbal fluency, participant performance significantly improved when
      completing only alternate forms. No significant practice effects were observed on
      tests of spatial processing. Practice effects caused by item-specific practice
      may be reduced via alternate test forms. However, similar reductions will be less
      apparent when practice effects are the result of test-specific practice.

PMID- 11989726
TI  - Cognitive functions of young adults who survived childhood cancer.
AB  - Neuropsychological tests were used to determine the cognitive functioning of
      adult long-term survivors treatedfor childhood cancer Disease onset before the
      age of 5 was related to lower test scores in intelligence tests, several memory
      tests, and motor function tests. The cranial irradiated survivors displayed more
      difficulties, especially in short-term memory tests and the Wechsler Adult
      Intelligence Scale Digit Symbol Test as compared to nonradiated survivors. No
      statistically significant differences in test scores were observed between
      different forms of cancer The results of this study are consistent with the
      notion that those memory types that demand special attention and motor speed
      functions are especially vulnerable to cancer and its treatment.

PMID- 11989727
TI  - How low is too low, revisited: sentence repetition and AVLT-recognition in the
      detection of malingering.
AB  - Sentence Repetition (SR) and Rey Auditory Verbal Learning Test-Recognition Task
      (AVLT-R) scores of 5 groups of examinees (severe traumatic brain injury [TBI],
      mild TBI nonlitigants, normal controls, mild TBI litigants, and actors) were
      compared with the intent of determining cutoffs for the detection of malingering.
      Cutoff scores were set below the minimum of the severe TBI group, resulting in a
      specificity of 100% for both tests. At this level of specificity, the AVLT-R
      detected 10 of the 20 known actors (50% sensitivity), whereas SR correctly
      identified 14 of the 20 actors (70% sensitivity). Among litigants with mild
      injury, 12.24% were identified by the AVLT-R and 6.12% by SR as malingerers.
      These findings are similar to those found utilizing a variety of other common
      neuropsychological instruments. Employing commonly used neuropsychological tests
      as measures of motivation is both practical and clinically useful.

PMID- 11989728
TI  - Rehabilitation of Balint's syndrome: a single case report.
AB  - Very little research has been done in the area of rehabilitation of the visual
      perceptual deficits observed after Balint's syndrome. This syndrome is
      characterized by difficulties with visual scanning, dysmetria secondary to visual
      perceptual deficits, and an inability to perceive more than 1 object at a time.
      This article describes the effects of a neuropsychological treatment protocol on
      a 23-year-old patient who suffered a fat embolism involving the territory of the
      posterior cerebral arteries. A neuropsychological evaluation carried out 12
      months after the brain embolism disclosed Balint's syndrome, alexia without
      agraphia, visual agnosia, prosopagnosia, and memory impairments. The
      rehabilitation protocol included both visuoperceptual retraining and a functional
      program designed to provide rehabilitation in contexts that were meaningful to
      the patient. After 1 year of treatment, a second neuropsychological evaluation
      was carried out. Significant improvement was demonstrated in terms of both
      objective testing and the return of an integrated and productive lifestyle.

PMID- 11989729
TI  - Preliminary analyses of Hebrew verbal fluency measures.
AB  - Hebrew language versions of phonemic and semantic fluency were administered to
      samples of normal control participants and individuals who had been hospitalized
      for 24 hr following a head injury. For the control sample, verbal fluency tasks
      were normally distributed and significantly correlated with education. The head
      injury sample's word generation was significantly lesser than that of the
      control's and not at all related to educational attainment. The findings provide
      evidence for the use of Hebrew fluency measures for clinical assessment and the
      need for collection of normative data across education levels.

PMID- 11989730
TI  - Age-related decline in perception of prosodic affect.
AB  - Perception of affect in speech is an important aspect of language, often
      conveying more about the intent of the speaker than semantic content. Impairment
      of perception of affect is seen in patients with right-hemisphere lesions.
      Nevertheless, little attention is paid to perception of emotional prosody in
      clinical neuropsychology. We present data concerning a revised version of the
      Emotional Perception Test (EPT-R), which indicates that older participants are
      significantly worse in prosodic perception than IQ-matched younger participants.
      The apparent age-related differences in perception of prosody are similar in
      magnitude to those seen on memory tests.

PMID- 11989731
TI  - Secretory patterns of growth hormone in dogs: circannual, circadian, and
      ultradian rhythms.
AB  - The objective was to characterize the circannual, circadian, and ultradian
      secretory patterns of growth hormone (GH) in intact crossbred and purebred dogs.
      In all experiments, blood samples were collected with minimal stress by direct
      peripheral venipuncture and GH was measured in plasma by a homologous
      radioimmunoassay. For circannual studies, samples were collected monthly from 6
      male dogs between 15:00 and 17:30 h over a 1-year time span. For circadian
      studies, blood samples were collected at 145-minute intervals from 09:00 to 06:45
      h of the following day in 14 female dogs. In ultradian experiments, blood samples
      were collected at 15-minute intervals for 2.5 h (15:00 to 17:30 h) in 7 males and
      7 females. Plasma GH in male dogs remained without change in summer, autumn, and
      winter but declined (P < 0.01) in spring (LSM +/- SEM; 6.9 +/- 0.5; 6.0 +/- 0.5;
      6.3 +/- 0.5; 4.3 +/- 0.5 ng/mL, respectively). No plasma GH circadian rhythmicity
      was detected. Nor was any ultradian pattern evident in either males or females.
      No gender-related differences were observed in ultradian GH plasma profiles. It
      is concluded that, while basal GH levels show seasonal fluctuations in dogs,
      neither circadian nor ultradian GH secretory fluctuations were present in the
      dogs assessed.

PMID- 11989732
TI  - Comparison of reverse transcription polymerase chain reaction,
      immunohistochemistry, and in situ hybridization for the detection of porcine
      epidemic diarrhea virus in pigs.
AB  - Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry,
      and in situ hybridization were compared for the detection of porcine epidemic
      diarrhea virus (PEDV). Fifteen piglets experimentally infected with PEDV were
      used in the study. In addition, 94 diarrheic piglets submitted to the Department
      of Veterinary Pathology in Seoul National University for diagnosis of PEDV
      infection were used to compare the 3 methods. Antigen and nucleic acid of PEDV
      were detected in 15/15, 13/15, and 14/15 of the intestinal and fecal samples from
      the PEDV-inoculated pigs by RT-PCR, immunohistochemistry, and in situ
      hybridization, respectively. The virus was isolated from 15/15 of the jejunal
      samples from the PEDV-inoculated pigs. Neither PEDV antigen nor PEDV nucleic acid
      was detected in the intestinal and fecal samples from mock-infected control pigs.
      Of the 94 samples, 63 were positive for PEDV by all 3 techniques. Six samples
      were positive for PEDV by immunohistochemistry and in situ hybridization. Three
      samples were positive for PEDV by in situ hybridization and RT-PCR. Seven samples
      were positive for PEDV by RT-PCR. Although RT-PCR identified the presence of PEDV
      more frequently than the other methods, when only formalin-fixed tissues are
      submitted, immunohistochemistry and in situ hybridization would be useful methods
      for the detection of PEDV antigen and nucleic acid.

PMID- 11989733
TI  - Comparison of embryonated chicken eggs with MDCK cell culture for the isolation
      of swine influenza virus.
AB  - Embryonated chicken eggs (ECE) and the Madin-Darby canine kidney (MDCK) cell line
      were compared for isolation of swine influenza virus (SIV) from nasal swabs and
      tissue samples. Samples originated from 30 pigs experimentally inoculated with 2
      x 106 to 2 x 10(7) embryo infectious dose 50% (EID50)/mL of swine influenza
      strain A/Swine/Indiana/1726/88 (H1N1). The results were analyzed with McNemar's
      chi-squared test for symmetry. The results indicated that more samples were SIV
      positive with ECE than with tissue culture (P < 0.001), suggesting that ECE
      remains the system of choice for isolation of SIV. It is recommend that routine
      use of both SIV isolation systems will increase the sensitivity of detection of
      virus shedding by considering the differences in growth and tropism of diverse
      SIV strains.

PMID- 11989734
TI  - Foot-and-mouth disease eradication efforts in the Republic of Korea.
AB  - On March 20, 2000, a suspected vesicular disease in cattle was reported to the
      National Veterinary Research and Quarantine Service (NVRQS) of the Republic of
      Korea. This represented the index case of a foot-and-mouth disease (FMD)
      outbreak, which spread through several provinces. The Republic of Korea had been
      free of FMD for 66 years prior to the reintroduction of the virus and had
      recently suspended imports of pork and pork products from neighboring Japan owing
      to a reported FMD out-break in that country. The Korean outbreak was ultimately
      controlled through the combination of preemptive slaughter, animal movement
      restrictions, and a strategy of ring vaccination. The purpose of this paper is to
      review the current FMD situation in Korea in the aftermath of its 2000 epizootic
      and how it may affect future efforts to eradicate or reduce risk of
      reintroduction of the disease into Korea.

PMID- 11989735
TI  - Blood and milk cellular immune responses of mastitic non-periparturient cows
      inoculated with Staphylococcus aureus.
AB  - Lymphocyte function and phenotype of peripheral blood and mammary gland cells
      were evaluated in non-periparturient cows before and at 1, 4 to 8 and 9 to 14 d
      after inoculation with Staphylococcus aureus, as expressed by percentage of CD3+,
      CD2+, and CD45R+ cells, antigen density of these markers per lymphocyte, and
      mitogen-induced blastogenesis. Milk bacterial counts and somatic cell counts
      (SCC) were also assessed. Mitogen-induced blastogenic responses were strong in
      blood and weak in mammary gland cells in all observations and positively
      correlated with the percent of CD45R+ cells. Significantly greater percentages of
      milk CD3+ lymphocytes and increased CD3, CD2, and CD45R antigen density per cell
      were observed after challenge. The blood CD3 and CD2 antigen density per
      lymphocyte and the milk CD2+ lymphocyte percent were negatively correlated with
      SCC (P < or = 0.01). No mastitis (SCC < or = 500 000 cells/mL) was observed in
      cows showing blood lymphocyte CD2 and CD3 antigen density indices < or = 2.5 and
      6, respectively. Forty-one percent of SCC values were predicted by the combined
      blood CD2 and milk CD3 antigen density (P < or = 0.01). These findings support
      the hypotheses that mitogen-induced lymphocyte blastogenesis is not a valid test
      to assess mammary gland immunocompetence and that CD2 expression may facilitate
      immune responses by decreasing the number of T cell receptors required to achieve
      full activation.

PMID- 11989737
TI  - Presentation of postweaning Escherichia coli diarrhea in southern Ontario,
      prevalence of hemolytic E. coli serogroups involved, and their antimicrobial
      resistance patterns.
AB  - Post-weaning Escherichia coli diarrhea (PWECD) in Ontario was investigated using
      a case-control study involving 50 Ontario nurseries. The clinical signs and the
      impact on productive parameters were determined by means of a producer survey.
      The hemolytic E. coli serogroups involved in PWECD (O149:K91:K88) were examined
      in this study. Based on a polymerase chain reaction test, the hemolytic E. coli
      from 82% of the case herds were positive for 3 enterotoxins (STa, STb, and LT),
      those from 12% of the case herds were positive for STb and LT only, and those
      from one herd (6%) were positive for 3 enterotoxins, as well as for verotoxin and
      F18 pili. The E. coli involved in disease were resistant to multiple antibiotics.
      Case farms commonly used a wide variety of antibiotics either in the feed or
      water, or as injectable drugs. The most common antibiotic used to treat PWECD on
      the study farms was apramycin, but evidence of resistance to this antibiotic was
      noted. The PWECD problem was commonly seen within a week of weaning but onset of
      diarrhea was reported as late as the grower-finisher stage. Growth rate was
      poorer in case herds and mortality was higher than in control herds,
      demonstrating that PWECD is an economically important disease in Ontario.

PMID- 11989736
TI  - Pathogenic Shiga toxin-producing Escherichia coli in the intestine of calves.
AB  - The purpose of this study was to compare the pathological effects of Shiga toxin
      producing Escherichia coli (STEC) that vary in their association with bovine and
      human disease. Shiga toxin-producing E. coli of serotypes associated with both
      dysentery in calves and hemolytic uremic syndrome (HUS) in humans (O5:H-,
      O26:H11, O111:H-,O113:H21) were compared with O157:H7 STEC, which are associated
      with HUS in humans but not with disease in calves. The STEC were administered
      orally to 80 day-old chicks and into ligated loops in the ileum and colon of four
      2- to 6-day-old calves. Examination of the ceca of the chickens 10 d
      postchallenge showed no adherence or tissue abnormality for any isolate. The
      calves were euthanized 8 to 10 h postinoculation, and sections of the intestinal
      loops were examined by light microscopy, transmission and scanning electron
      microscopy, and immunohistochemistry. All strains showed consistent focal
      adherence associated with mild lesions in the colon. Attaching and effacing
      lesions were observed with the eae-positive strains. Ileal lesions were similar
      to the colonic ones but were sometimes severe, with marked polymorphonuclear
      leukocyte proliferation in the lamina propria. It is concluded that chickens were
      unsuitable for studying interaction of STEC with the intestine and that there was
      no difference in the interaction of the ligated calf intestine with STEC of
      serotypes associated with disease in calves compared with O157:H7 STEC.

PMID- 11989738
TI  - Mycoplasma hyopneumoniae colonization of pigs sired by different boars.
AB  - Differences in Mycoplasma hyopneumoniae colonization were evaluated in
      experimentally inoculated pigs sired by 3 different boars of the same genetic
      line. Forty-six pigs were used, including a treatment group and positive and
      negative control groups. The pigs were intratracheally inoculated with an M.
      hyopneumoniae suspension or with Friis media as a placebo. To evaluate
      differences in the magnitude of colonization during a 35-day period, nasal and
      tracheal swabs were collected weekly and tested by nested polymerase chain
      reaction (N-PCR). Temperature, weight and circulating antibodies were measured
      for 35 days. At 11 and 35 d postinoculation the pigs were necropsied and
      macroscopic and microscopic lesions were determined. A section of bronchus was
      tested by the indirect immunofluorescence test (IFAT), scanning electron
      microscopy (SEM) and N-PCR. The N-PCR results from the nasal and tracheal swabs
      showed that the pigs sired by one boar (B3) had a distinctive colonization
      pattern, different from that of the pigs from the other 2 boars and from the
      positive controls. SEM studies demonstrated that at 35 d postinoculation a higher
      proportion of B3 pigs had lower numbers of mycoplasmas attached to the cilia
      compared with B1 and B2 offspring. No significant differences were observed in
      temperature and weight gain among groups by ANOVA; however, with use of a 2 x 2
      table, temperature differences were observed between pigs sired by boars B1 and
      B2 at 4 d postinoculation. No pigs seroconverted, showed gross or microscopic
      lesions, or had positive IFAT results. These results provide evidence of
      differences in patterns of colonization between pigs sired by different boars,
      suggesting a possible genetic effect.

PMID- 11989739
TI  - Biofilm bacteria: formation and comparative susceptibility to antibiotics.
AB  - The Calgary Biofilm Device (CBD) was used to form bacterial biofilms of selected
      veterinary gram-negative and gram-positive pathogenic bacteria from cattle,
      sheep, pigs, chicken, and turkeys. The minimum inhibitory concentration (MIC) and
      minimum biofilm eradication concentration (MBEC) of ampicillin, ceftiofur,
      cloxacillin, oxytetracycline, penicillin G, streptomycin, tetracycline,
      enrofloxacin, erythromycin, gentamicin, tilmicosin, and trimethoprim-sulfadoxine
      for gram-positive and -negative bacteria were determined. Bacterial biofilms were
      readily formed on the CBD under selected conditions. The biofilms consisted of
      micro-colonies encased in extracellular polysaccharide material. Biofilms
      composed of Arcanobacterium (Actinomyces) pyogenes, Staphylococcus aureus,
      Staphylococcus hyicus, Streptococcus agalactiae, Corynebacterium renale, or
      Corynebacterium pseudotuberculosis were not killed by the antibiotics tested but
      as planktonic bacteria they were sensitive at low concentrations. Biofilm and
      planktonic Streptococcus dysgalactiae and Streptococcus suis were sensitive to
      penicillin, ceftiofur, cloxacillin, ampicillin, and oxytetracycline. Planktonic
      Escherichia coli were sensitive to enrofloxacin, gentamicin, oxytetracycline and
      trimethoprim/ sulfadoxine. Enrofloxacin and gentamicin were the most effective
      antibiotics against E. coli growing as a biofilm. Salmonella spp. and Pseudomonas
      aeruginosa isolates growing as planktonic populations were sensitive to
      enrofloxacin, gentamicin, ampicillin, oxytetracycline, and
      trimethoprim/sulfadoxine, but as a biofilm, these bacteria were only sensitive to
      enrofloxacin. Planktonic and biofilm Pasteurella multocida and Mannheimia
      haemolytica had similar antibiotic sensitivity profiles and were sensitive to
      most of the antibiotics tested. The CBD provides a valuable new technology that
      can be used to select antibiotics that are able to kill bacteria growing as
      biofilms.

PMID- 11989740
TI  - In vitro expression of tumor necrosis factor-alpha, interleukin 1beta, and
      interleukin 8 mRNA by bovine macrophages following exposure to Porphyromonas
      levii.
AB  - The objective was to evaluate the pro-inflammatory response of bovine macrophages
      towards Porphyromonas levii, an etiologic agent of acute interdigital phlegmon,
      by evaluating the mRNA expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin 1beta (IL-1beta), and interleukin 8 (IL-8). Bovine macrophages detect
      the presence of bacteria, such as P. levii, and respond by upregulating
      transcription of the genes for pro-inflammatory cytokines TNF-alpha and IL-1beta
      in addition to the neutrophil chemoattractant IL-8. Monocytes were isolated from
      blood obtained from Holstein steers. These cells were cultured and differentiated
      into macrophages over 7 d, followed by exposure to P. levii, Escherichia coli
      lipopolysaccharide (LPS), or tissue culture medium for 1, 1.5, 2, 4, 6, 8,12, or
      24 h. Total RNA was extracted, and reverse transcriptase polymerase chain
      reaction was conducted to examine the presence of TNF-alpha, IL-1beta, or IL-8
      mRNA. Products were visualized on agarose gels to determine the presence or
      absence of cytokine mRNA amplified DNA. Bovine macrophages, when exposed to P.
      levii or E. coli LPS, produced mRNA for TNF-alpha, IL-1beta, and IL-8. Expression
      of all 3 cytokines was higher in the P. levii and LPS-exposed macrophages at all
      time points examined, compared with tissue culture medium-treated cells.
      Expression of these cytokines by macrophages is likely directly involved in
      orchestration of the immune response, and particularly in neutrophil recruitment
      to affected tissues in acute interdigital phlegmon.

PMID- 11989741
TI  - Comparison of different methods for diagnosis of porcine proliferative
      enteropathy.
AB  - The objectives of this study were: (1) to compare 2 methods of serology; (2) to
      compare 3 histologic techniques; and (3) to compare 2 methods of detecting
      shedding in pigs experimentally challenged with Lawsonia intracellularis. The
      sensitivities of these tests were determined by the detection of infection. Forty
      5-week-old pigs were inoculated on day 0 with intestinal homogenate from pigs
      with proliferative enteropathy (PE). Clinical evaluation was done on day 7 and
      daily from day 14 to 28 postinoculation. Fecal shedding of L. intracellularis was
      monitored by use of polymerase chain reaction (PCR) analysis and immunoperoxidase
      staining at 7-day intervals. Serum was obtained on days 0 and 28 for serologic
      testing by glass slide and tissue culture indirect fluorescent antibody tests. At
      euthanasia on day 28, gross intestinal lesions were evaluated and ileum samples
      collected for histologic analyses. Ileal histologic sections from each animal
      were stained by hematoxylin and eosin, Warthin-Starry silver stain, and
      immunohistochemistry (IHC). Of the 40 pigs, 36 had gross lesions typical of PE at
      necropsy. The percentage of agreement between the 2 serologic methods was 94.4%.
      Immunoperoxidase stain of fecal smears was more sensitive than PCR for detecting
      fecal shedding, especially on day 21 (89.5% and 60.5%, respectively) and day 28
      (59.4% and 37.5%, respectively) post-inoculation. The IHC stain was much more
      sensitive for detecting infection than the routinely used hematoxylin and eosin
      and Warthin-Starry silver stains. In conclusion, in experimentally infected pigs,
      both serologic methods were appropriate techniques for detecting infection. For
      fecal samples, PCR has low sensitivity. Immunohistochemistry is the best
      diagnostic tool for formalin-fixed samples.

PMID- 11989742
TI  - Environmental incubation factors influence embryonic thyroid hormones.
AB  - Thyroid hormone responses in embryonic avian species are of two types,
      developmental and metabolic. Many studies have characterized the developmental
      function of the turkey embryonic thyroid, but few have characterized the
      metabolic function. Therefore, the purpose of this study was to describe the
      response of turkey embryonic thyroid hormones to three environmental factors. We
      proposed that embryonic thyroids from different genetic backgrounds would respond
      differently to changes in maternal diet and incubation temperature. Lines of
      turkeys known to have different embryonic growth and survival were examined in
      the current study. These eggs differ in egg weight, eggshell conductance,
      hatchling weight and organ maturity at the time of hatching. Eggs were produced
      throughout a 20 wk laying period and embryos were sampled at monthly intervals.
      Half of the hens producing the eggs were fed additional iodide in their diets,
      then, subsequently, half of each dietary treatment and line combination were
      incubated at either 36.8 C or 37.5 C to prolong the incubation period. Embryos
      were sampled during the final week of incubation when thyroid hormones become
      elevated to effect maturation and survival functions in turkey embryos. Embryonic
      thyroxine (T4) and triiodothyronine (T3) levels were assayed by RIA and compared
      among the treatments. Line, diet, and incubation period interacted to affect the
      levels of T4, T3 and T3 to T4 ratios in the turkey embryonic during late
      incubation. It was concluded that environmental factors can affect circulating
      thyroid hormone levels in turkey embryos, thus affecting metabolic functions, and
      the possibility exists to manipulate these circulating levels using environmental
      incubation conditions to improve hatchability.

PMID- 11989743
TI  - Effects of density and perch availability on the immune status of broilers.
AB  - This study attempted to evaluate the effect of various housing densities and
      perch availability on the immune status of commercial broilers. Birds were raised
      from hatch to 42 d of age with 10, 15, and 20 birds/m2 in pens, with and without
      the availability of horizontal perches. The immune parameters that were assessed
      were lymphoid organ weights, antibody response to SRBC in the last 10 d of
      growth, heterophil:lymphocyte ratios at 32 and 42 d of age, and lymphocyte
      blastogenesis of peripheral blood lymphocytes collected at 32 and 42 d of age. As
      density increased, bursa weight and bursa/body weight ratios decreased
      significantly (P < 0.05). Addition of perches to the pens also significantly
      decreased the bursa weights and bursa/body weight index (P < 0.01). No other
      significant effects were observed for the flock performance, morphometric data,
      or immunological tests between treatments. We concluded that under the conditions
      of this study, which tried to simulate commercial conditions, the bursal weight
      was the best indicator of stress that was related to housing density. Addition of
      perches appeared to increase this level of stress because the birds used the
      perches infrequently, and therefore there might have been a further reduction in
      the availability of floor space to the birds.

PMID- 11989744
TI  - Effect of dietary supplemental levels of vitamin A on the egg production and
      immune responses of heat-stressed laying hens.
AB  - Two experiments were conducted to evaluate the effect of vitamin A
      supplementation of a commercial layer diet on the laying performance and immune
      function of heat-stressed hens. In Experiment 1, two different levels of vitamin
      A supplementation (3,000 and 9,000 IU/kg) were used to investigate the laying
      performance and antibody titer against Newcastle disease virus (NDV) of heat
      stressed hens. Results showed that the high level of vitamin A supplementation
      (9,000 IU/kg) had a beneficial effect on the feed intake and laying rate of heat
      stressed hens (P < 0.05), compared with the control group (3,000 IU/kg). The
      antibody titers were not influenced by the level of vitamin A (P > 0.05). In
      Experiment 2, the effect of four levels of vitamin A (3,000, 6,000, 9,000, and
      12,000 IU/kg) on the antibody titer to NDV and T lymphocyte proportion was
      studied. The experimental birds were exposed to a high temperature (31.5 C) 15 d
      after NDV vaccination (Treatment 1) or immediately (Treatment 2). The results
      showed that the egg weight was increased (P < 0.01) by the high levels of vitamin
      A supplementation (6,000 and 9,000 IU/kg), but feed intake, laying rate, and body
      weight loss were not (P > 0.05). In Treatment 1, vitamin A had no significant
      effect on antibody titers against NDV in normal or hot environments but increased
      (P < 0.01) the proportion of alpha-naphthyl acetate esterase (ANAE)-positive
      cells. Vitamin A supplementation had a significant effect on NDV antibody titer
      and ANAE-positive cell proportion in Treatment 2 (P < 0.01). The results of the
      present study suggested that vitamin A supplementation in commercial layer diets
      to layer chickens under heat stress was beneficial to laying performance and
      immune function.

PMID- 11989745
TI  - Growth performance of broilers using a phase-feeding approach with diets switched
      every other day from forty-two to sixty-three days of age.
AB  - Phase-feeding (PF; Treatment 2) was tested relative to an NRC regimen (Treatment
      1) to evaluate the impact of PF on broilers during the finisher period (42 to 63
      d). Two modified PF treatments were also tested during this experiment: Treatment
      3 involved lowering the amino acid requirements predicted with PF linear
      regression equations by 10% (PF10), Treatment 4 involved increasing the slope of
      the linear regression equations by 15% (PF15). Broilers fed Treatment 1 consumed
      a single diet throughout the experiment, whereas PF treatments were fed in a
      series of 11 diets in which feed was switched every other day, resulting in
      steadily decreasing lysine, SAA, and threonine levels. On Day 63, weight gain,
      feed intake, feed efficiency, and crude protein intake did not differ (P > 0.05)
      among birds fed PF treatments and Treatment 1. Digestible lysine and threonine
      intakes were increased (P < 0.05) for Treatment 1 relative to the PF treatments,
      and digestible SAA intake for the NRC treatment was increased (P < 0.05) relative
      to the PF10 and PF15 treatments. Compared to Treatment 1, no differences (P >
      0.05) in percentage breast, wing, leg, or abdominal fat were observed when birds
      were fed PF, PF10, or PF15 diets. These results indicate that PF supports maximum
      growth performance during an extended finisher period, even when lysine, SAA, and
      threonine levels are reduced every other day. Economic analysis indicated that PF
      regimens may lead to savings ($ per kg weight gain or breast meat).

PMID- 11989746
TI  - Protein and lipid deposition rates in male broiler chickens: separate responses
      to amino acids and protein-free energy.
AB  - Two experiments of similar design were conducted with male broiler chickens over
      two body weight ranges, 200 to 800 g in Experiment 1 and 800 to 1,600 g in
      Experiment 2. The data were used to test the hypothesis that protein deposition
      rate increases (linearly) with increasing amino acid intake, until energy intake
      becomes limiting for protein deposition rate. Additional amino acid intake above
      this point would be deposited less efficiently. An increase in energy intake
      would increase lipid deposition rate, but should, at low amino acid intakes, not
      affect protein deposition rate. Each experiment consisted of 18 treatments: two
      levels of protein-free energy (energy(pf)) intake, combined with nine amino acid
      to energypf ratios. Protein was balanced for amino acid content and lysine was
      the first limiting amino acid in the diet. Protein deposition rate increased with
      additional amino acid intake. No evidence was found that energy(pf) intake
      limited protein deposition rate at high amino acid intake. Extra intake of
      energy(pf) increased lipid deposition rate, which was independent of amino acid
      intake. Where amino acid intake was limiting, additional intake of energy(pf) had
      generally no effect on protein deposition rate. The marginal efficiency of amino
      acid utilization for protein deposition did not depend on body weight. The facts
      are relevant to the modeling of the growth of broiler chickens.

PMID- 11989747
TI  - A comparison of quadratic versus segmented regression procedures for estimating
      nutrient requirements.
AB  - Continued improvements in dietary formulation will require increasingly detailed
      knowledge of nutrient requirements. The objective of this study was to evaluate
      bias and precision of estimates of nutrient requirements from quadratic versus
      segmented regression. One hundred 0-to-3-wk turkey growth experiments were
      simulated to provide data with known nutrient requirements. Nine diets contained
      levels of an arbitrary nutrient ranging from 80 to 120% of recommended. The true
      nutrient requirement was uniformly randomly distributed between 90 and 110% of
      recommended. The requirements were estimated as the intersection of the segmented
      regression lines from a two-slope model, and 0.90 and 0.95 of the maximum gain
      predicted from quadratic regression coefficients. The mean true requirement was
      99.42%, and predictions were 102.14+/-0.61, 107.81+/-0.61, and 99.59+/-0.61% for
      0.90 of quadratic maximum, 0.95 of quadratic maximum and segmented regression,
      respectively. The segmented regression resulted in the closest prediction to the
      true nutrient requirement in 73 of 100 replicates. The average squared deviation
      of the requirement from their estimates were 15.18 for 0.90 of quadratic maximum,
      78.72 for 0.95 of quadratic maximum, and 2.41 for segmented regression. The
      quadratic regressions yielded overestimates, particularly when the experimental
      diets were not centered on the requirement, suggesting that a bias can be
      introduced by experimental design. Segmented regression procedures resulted in
      more precise estimates of nutrient requirements, were less likely to suffer from
      bias, and required less a priori knowledge of the true requirement than did
      quadratic regression procedures.

PMID- 11989748
TI  - Ideal ratio (relative to lysine) of tryptophan, threonine, isoleucine, and valine
      for chicks during the second and third weeks posthatch.
AB  - Six bioassays were conducted to determine the ideal ratios of several amino acids
      relative to Lys. Young male crossbred chicks were fed diets based on corn gluten
      meal and synthetic amino acids that could be made singly deficient in Lys, Trp,
      Thr, Ile, or Val. Diets for all assays contained 3,400 kcal ME/kg, and L-glutamic
      acid was used to make all diets (within and among assays) equal in crude protein
      at 22.5% of the diet. True digestibility assessment of corn gluten meal in
      cecectomized roosters facilitated dose-titration studies so that least squares
      fitted one-slope broken-lines and quadratic regression equations could be
      calculated to establish inflection points for weight gain and gain:feed. Four
      battery pens of four chicks were fed one of six amino acid levels from 8 to 21 or
      22 d posthatching. Weight gain and gain:feed responded quadratically (P < 0.01)
      to increasing doses of digestible Lys (0.68 to 1.28%), Trp (0.09 to 0.24%), Thr
      (0.41 to 0.81%), Ile (0.45 to 0.95%), and Val (0.51 to 1.06%). Broken-line least
      squares analysis predicted breakpoints for gain and gain:feed, respectively, of:
      Lys (0.85, 0.96%), Trp (0.16, 0.16%), Thr (0.53, 0.53%), Ile (0.59, 0.58%), and
      Val (0.74, 0.74%). The intercept of the quadratic regression curve and the
      plateau of the broken line predicted digestible Lys requirements for gain and
      gain:feed, respectively, of 0.95 and 1.03%. Similar calculations predicted
      digestible Trp requirements of 0.18% for gain and gain:feed, digestible Thr
      requirements of 0.59% for gain and 0.60% for gain:feed, digestible Ile
      requirements of 0.68% for gain and gain:feed, and digestible Val requirements of
      0.81% for gain and 0.82% for gain:feed. Regardless of curve-fitting method,
      gain:feed requirements for Lys were much higher than weight gain requirements.
      Using the higher of the broken-line requirement estimates for gain and gain:feed,
      ideal ratios (% of Lys) were as follows: Lys (100), Trp (16.6), Thr (55.7), Ile
      (61.4), and Val (77.5).

PMID- 11989749
TI  - The effect of dietary carnitine on semen traits of white Leghorn roosters.
AB  - Carnitine has antioxidant properties that protect sperm membranes against toxic
      reactive oxygen species. Carnitine also functions to reduce the availability of
      lipids for peroxidation by transporting fatty acids into the mitochondria for
      beta-oxidation to generate adenosine triphosphate (ATP) energy. Because the
      effects of this supplemental amino acid on the reproductive performance of the
      avian breeder male are unknown, the objective of the current study was to
      evaluate the antioxidant role of dietary L-carnitine on semen traits and
      testicular histology in Leghorn breeder roosters. Two experiments were conducted
      in which birds were fed a control diet or one supplemented with 500 mg of
      carnitine/kg of diet. For Experiment 1, dietary treatments were fed to older
      birds (n = 12 birds/treatment) when they were 58 to 62 wk of age. For Experiment
      2, younger birds were fed dietary treatments between 32 to 37 wk of age (n = 14
      experimental units/treatment with three roosters composing an experimental unit
      for a total of 84 roosters). Semen traits and lipid peroxidation of sperm,
      determined by measuring malonaldehyde, were examined weekly. Feeding dietary
      carnitine to young and aging White Leghorn roosters ad libitum for 5 wk not only
      improved sperm concentration during the last half of supplementation but also
      reduced sperm lipid peroxidation. Testicular tissue of birds fed dietary
      carnitine for 5 wk was preserved as indicated by a reduction in multinucleated
      giant cells. These results suggest that dietary carnitine has antioxidant
      properties that may preserve sperm membranes in roosters, thereby extending the
      life span of sperm.

PMID- 11989750
TI  - Impact of phase-feeding on the growth performance of broilers subjected to high
      environmental temperatures.
AB  - Experiments were conducted to evaluate the effects of phase feeding (PF) on
      broilers subjected to heat stress during the grower and finisher periods. Birds
      were fed diets containing lysine, sulfur amino acid (SAA), or threonine levels
      based on NRC (1994) recommendations or predictions from linear regression
      equations (PF). With PF, diets were switched every other day, resulting in
      steadily decreasing lysine, SAA, and threonine levels. In Experiment 1 (42 to 56
      d), growth performance was unaffected (P > 0.05) by diet, and cost per kilogram
      of weight gain did not differ (P > 0.05) between treatments. In Experiments 2 (23
      to 42 d) and 3 (42 to 63 d) birds were housed in environmental chambers and
      subjected to high (15 h at 35 C, 9 h at 23.9 C) or normal (23.9 C) temperatures.
      In both experiments, heat stress reduced (P < 0.05) growth performance and
      increased (P < 0.05) percentage leg yield. Moreover, heat stress decreased
      percentage breast yield (P < 0.05) in Experiment 2. Growth performance and
      carcass yield were unaffected (P > 0.05) by PF relative to birds fed NRC-based
      diets, with the exception of feed efficiency, which was reduced (P < 0.05) by PF
      under normal temperatures in Experiment 2. Data indicated that dietary lysine,
      SAA, and threonine levels may be reduced every other day under a PF program
      without adversely affecting growth performance or carcass yield of birds exposed
      to high environmental temperatures. Cost analysis indicated that savings might be
      available with PF under high temperature conditions.

PMID- 11989751
TI  - Dietary polyunsaturated fatty acids decrease fat deposition in separable fat
      depots but not in the remainder carcass.
AB  - Two experiments were conducted in order to determine the effect of dietary fatty
      acid profile on deposition of body fat, carcass fat, and separable fat depots.
      Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an
      inclusion level of 10% were administered to female broiler chickens. In
      Experiment 1, total body fat, carcass fat (total body fat minus abdominal fat),
      and abdominal fat (AF) were determined. In Experiment 2, several separable fat
      depots (abdominal, neck, sartorial, and mesenteric fat) were removed and weighed.
      In general, the analyzed separable fat depots were reduced in broilers fed
      sunflower or linseed oils with respect to those fed tallow or olive oil (P <
      0.05). Percentages of body and carcass fat were also slightly reduced in birds
      fed sunflower or linseed oil, with respect to those fed tallow; however, the
      differences were not statistically significant. Regression analysis showed that
      body fat, carcass fat, and fat depots variability were closely correlated with AF
      (R2 = 0.69, 0.56, and 0.81, respectively), except for birds fed tallow, in which
      abdominal and mesenteric fat showed a different growth pattern with respect to
      the other treatments and to the other fat depots. These results suggest that
      polyunsaturated fatty acids reduce fat deposition in separable fat depots with
      respect to monounsaturated and saturated fats but not in the rest of the body fat
      depots. The growth pattern of fat depots can be modified by dietary fatty acid
      profile. Broilers fed saturated fat tend to deposit more fat in abdominal and
      mesenteric depots.

PMID- 11989752
TI  - Active immunization of broiler breeder hens with a recombinant chicken inhibin
      fusion protein enhances egg lay.
AB  - We have demonstrated that inoculation of female Coturnix with an inhibin-based
      immunogen (MBP-cINA521) accelerated puberty and enhanced hen-day egg production
      (HDEP). Herein, MBP-cINA521, a fusion protein, which consists of the bacterial
      maltose binding protein (MBP) and a fragment of the infinity-subunit of chicken
      inhibin (cINA521), was tested for its ability to enhance production performance
      in broiler breeders. Pullets (Arbor Acres Classic Females; n = 60 birds/treatment
      group) were given (subcutaneously) 0, 1, 3, or 5 mg of MBP-cINA521 in Freund's
      complete adjuvant at 20 wk and 4 d of age. Booster immunizations (one-half of the
      primary dosages) were given at 23 wk of age. The vehicle for controls (CON; no
      booster) and MBP-cINA521-boosted birds was Freund's incomplete adjuvant. Blood
      samples were obtained at the end of the trial to assess immunological response to
      the antigen with a titer ELISA. The onset of puberty was assessed by calculation
      of the average ages at first lay (FIRST) and at 50% egg production (FIFTY).
      Cumulative percentage HDEP was determined weekly throughout the laying period (40
      wk). Egg weight (EWT) and specific gravity (SG) assessments were made
      periodically during the trial. Body weight gain (BWG) and mortality (MORT) data
      were also collected. Significant injection treatment differences (P < 0.01) in
      inhibin antibody titers were detected according to the following order: low dose
      = intermediate dose > high dose > CON. A dose of MBP-cINA521 capable of
      accelerating puberty and increasing overall egg lay was identified. FIRST and
      FIFTY responses were decreased (P < 0.05) in birds given the intermediate dose
      (3.0 mg) of MBP-cINA521 when compared to the CON. FIFTY responses were also lower
      (P < 0.05) than CON responses in those birds given the highest dose (5.0 mg) of
      the inhibin antigen. Cumulative HDEP was also higher (P < 0.05), beginning at 3
      wk of lay and weekly thereafter (P < 0.05, for the remaining 40 wk), in birds
      given the intermediate immunogen dosage when compared to the CON. By Week 40, an
      average increase of 9.5% HDEP was realized in birds given 3.0 mg of MBP-cINA521.
      MORT rates were similar in the CON and in the two lowest MBP-cINA521 treatment
      groups but were higher (P < 0.05) in those birds given 5.0 mg of the antigen.
      EWT, SG, and BWG measurements were unaffected by treatment with the inhibin
      vaccine. In agreement with our findings in quail, immunoneutralization of inhibin
      enhanced production performance in breeder hens.

PMID- 11989753
TI  - Localization of the fertilized germinal disc in the chicken egg before
      incubation.
AB  - At the time of oviposition, the embryo in the fertilized chicken egg has
      developed the germinal disc on top of the yolk and contains thousands of
      blastodermal cells. The germinal disc escapes exact localization because it is
      surrounded by albumen and shell membranes under a calcified shell. This study
      investigated whether or not ultrasonography or nuclear magnetic resonance imaging
      (MRI) are suited to localize the germinal disc and, if so, to estimate the
      accuracy of localization. Hatchability of treated eggs was also recorded. The
      ultrasound waves were reflected by the shell. The germinal disc could be seen
      only after removal of the eggshell and the outer shell membrane. In all, 39
      intact eggs, MRI localized the germinal disc within 2 mm thick image slices. The
      mean position of the germinal disc deviated 3.0+/-2.1 mm from the maximum
      vertical plane of the egg with a mean distance to the inner surface of the shell
      of 2.7+/-1.1 mm. Incubation resulted in 84.2 and 77.5% hatched chicks for imaged
      eggs and controls, respectively. The localization results of MRI were verified
      manually in 38 open shell cultures. Correlation coefficients for the position of
      the germinal disc were r = 0.86 to 0.99 for the x-axis, r = 0.75 to 0.89 for the
      y-axis, and r = 0.63 to 0.76 for the z-axis. The study thus shows that MRI is a
      reliable tool to localize the germinal disc within the intact freshly laid egg.

PMID- 11989754
TI  - Regional differences in transport, lipid composition, and fluidity of apical
      membranes of small intestine of chicken.
AB  - Na+-dependent D-glucose transport was studied in brush-border membrane vesicles
      from duodenum, jejunum, and ileum of 5- to 6-wk-old chickens. Regional
      differences were found, and both initial rates and accumulation ratio of D
      glucose were higher in the proximal part of the small intestine than in the
      ileum. To establish the mechanism(s) underlying these differences we have studied
      the density of Na+-dependent D-glucose cotransporter (SGLT1) as well as lipid
      composition and fluidity. Phlorizin-specific binding and Western blot analysis
      indicated a decrease in the amount of SGLT1 in the ileum when compared to the
      duodenum and jejunum. The distal part of the small intestine also showed a
      decrease in free cholesterol content and saturated-to-unsaturated fatty acid
      ratio together with an increase in lipid content and phosphatidylcholine-to
      sphingomyelin ratio. These results were associated with a decrease in the
      diphenylhextriene fluorescence polarization found in brush-border membranes of
      the ileum. We can conclude that the decrease in the apical D-glucose transport
      found in the ileum is primarily due to a reduction in the amount of SGLT1 present
      in the brush-border membrane rather than the differences in the lipid composition
      and fluidity.

PMID- 11989755
TI  - Association of mitochondrial function with feed efficiency within a single
      genetic line of male broilers.
AB  - Studies were conducted to determine relationships between feed efficiency and
      mitochondrial function and biochemistry. After feed efficiency (FE; gain:feed)
      was determined in broiler breeder males between 6 and 7 wk of age, mitochondria
      were isolated from breast and leg muscle from birds with high FE (0.83+/-0.01, n
      = 6) and low FE (0.64+/-0.01, n = 7). Respiratory chain coupling, assessed by the
      respiratory control ratio (RCR), was greater in high FE breast, and leg
      mitochondria provided NADH-linked, but not FADH-linked, energy substrates. There
      were no differences, however, in the adenosine diphosphate to oxygen (ADP:O)
      ratio (an index of oxidative phosphorylation) when mitochondria were provided
      either energy substrate. Electron leak, as determined by generation of H202, was
      greater in the low FE than in high FE breast mitochondria. Electron leak
      increased following inhibition of electron transport at Complex I (with rotenone)
      and Complex III (with antimycin A) in low FE but not in high FE breast
      mitochondria. There were no differences in basal electron leak in leg
      mitochondria between groups, but H202 generation was elevated (P < 0.07) compared
      to basal values in low FE leg mitochondria after Complex I inhibition. The
      activities of Complexes I and II were greater in high FE breast and leg muscle
      mitochondria compared to those in low FE mitochondria. The results indicate that
      lower respiratory chain coupling in low FE muscle mitochondria may be due to
      lower activities of Complexes I and II and defects in electron leak and provide
      insight into cellular mechanisms associated with the phenotypic expression of
      feed efficiency in broilers.

PMID- 11989756
TI  - Changes in the population of immunoreactive S-100-positive folliculo-stellate
      cells in hens during induced molting.
AB  - The goal of this study was to determine whether the population of folliculo
      stellate (FS) cells in the hen's pituitary change during induced molting. White
      Leghorn laying hens were subjected to induced molting by feed withdrawal; feeding
      was resumed on the fourth day after egg laying ceased. The anterior pituitaries
      were collected from hens at pretreatment, at 3 and 5 d after feed withdrawal and
      at 3 d after cessation of egg laying, 10 d after cessation of egg laying (6 d
      after resumption of feeding), on the day of and 1 wk after resumption of egg
      laying (RL and 1WRL, respectively). Pituitaries were processed to detect FS cells
      by immunocytochemistry for the S-100 protein. Sections were then examined under a
      light microscope with an image analysis computer system. S-100 immunoreactive
      cells were found in the cephalic and caudal lobes of the anterior pituitary in
      all groups of hens. The majority of S-100 immunoreactive cells formed clusters of
      cells that faced into the follicle and surrounded the glandular cells with long
      cytoplasmic processes. The S-100 immunoreactive area in the cephalic lobe was
      significantly increased in the RL group (P < 0.05), but decreased thereafter in
      1WRL group. The S-100-positive cell area in the caudal lobe did not show
      significant changes during induced molting. These results suggest that FS cell
      population is likely to increase at the final stage of induced molting and may be
      involved in control of pituitary functions for the resumption of ovulation.

PMID- 11989757
TI  - Effects of feed deprivation and electrical, gas, and captive needle stunning on
      early postmortem muscle metabolism and subsequent meat quality.
AB  - The general method for stunning poultry before slaughter is by immersion of a
      chicken's head into an electrified waterbath. This method results in carcass and
      meat quality deficiencies. The major problems are hemorrhages and a delay in
      onset of rigor mortis, which increases the risk of cold shortening with early
      deboning. In two experiments, this study examines the early postmortem metabolism
      in the breast muscle and its effect on ultimate meat quality. The first
      experiment describes the effects of 5 h feed deprivation on the availability of
      glycogen from the liver and the breast muscle, of waterbath and head-only
      electrical stunning on pH and metabolite levels up to 6 h in unprocessed muscle,
      and the consequences on meat quality. The second experiment compares the same
      measurements after waterbath and head-only electrical stunning, CO2/O2/N2 and
      Ar/CO2 gases, and captive needle stunning. Metabolic degradation halted after 6 h
      without processing or after 4 h under conventional conditions after waterbath and
      CO2/O2/N2 stunning. With other stunning methods, this occurrence is at a faster
      rate, largely depending on muscle activity. Muscle glycogen does not need to be
      exhausted for energy generation to cease. If glycogen is a limiting factor, as
      found with head-only stunning, pH drops too rapidly and affects water-holding
      capacity and color. Hemorrhage scores were higher with electrical stunning than
      with other stunning methods. Gas stunning affected color and, to a lesser extent,
      water-holding capacity. Captive needle stunning scored between gas and electrical
      stunning on most measurements.

PMID- 11989758
TI  - Development of brain damage as measured by brain impedance recordings, and
      changes in heart rate, and blood pressure induced by different stunning and
      killing methods.
AB  - Poultry are electrically stunned before slaughter to induce unconsciousness and
      to immobilize the chickens for easier killing. From a welfare point of view,
      electrical stunning should induce immediate and lasting unconsciousness in the
      chicken. As an alternative to electroencephalography, which measures brain
      electrical activity, this study used brain impedance recordings, which measure
      brain metabolic activity, to determine the onset and development of brain damage.
      Fifty-six chickens were surgically equipped with brain electrodes and a canula in
      the wing artery and were subjected to one of seven stunning and killing methods:
      whole body electrical stunning; head-only electrical stunning at 50, 100 or 150
      V; or an i.v. injection with MgCl2. After 30 s, the chickens were exsanguinated.
      Brain impedance and blood pressure were measured. Extracellular volume was
      determined from the brain impedance data and heart rate from the blood pressure
      data. An immediate and progressive reduction in extracellular volume in all
      chickens was found only with whole body stunning at 150 V. This treatment also
      caused cardiac fibrillation or arrest in all chickens. With all other electrical
      stunning treatments, extracellular volume was immediately reduced in some but not
      all birds, and cardiac fibrillation or arrest was not often found. Ischemic
      conditions, caused by cessation of the circulation, stimulated this epileptic
      effect. A stunner setting of 150 V is therefore recommended to ensure immediate
      and lasting unconsciousness, which is a requirement for humane slaughter.

PMID- 11989759
TI  - The characterization and incidence of pale, soft, and exudative broiler meat in a
      commercial processing plant.
AB  - Pale, soft, exudative (PSE) turkey meat is a growing problem for the industry of
      further processed poultry meat. The low pH condition due to rapid glycolysis
      while the body temperature is still high leads to protein denaturation, causing
      pale color and reduced water-holding capacity. This condition impacts product
      yield and quality. These studies were designed to estimate the incidence of PSE
      broiler meat in a commercial plant and to use response surface methodology to
      characterize the relationship between pH and lightness (at deboning and at 24 h
      postmortem), expressible moisture, drip loss, and cook loss. Pale fillets had
      significantly lower pH, greater L* values at 3 and 24 h postmortem, and higher
      expressible moisture, drip loss, and cook loss. The lower water-holding capacity
      of the pale fillets was characteristic of PSE meat. Additionally, L* values were
      measured on 3,554 boneless broiler breast fillets in a commercial processing
      line. By using the L* value range (>54) from the pale group of fillets as an
      indication of paleness, approximately 47% of the 3,554 fillets were pale and
      could potentially exhibit poor water-holding capacity. These results may not
      represent the entire industry but indicate that PSE chicken can represent a
      substantial proportion of commercially processed broiler meat.

PMID- 11989760
TI  - Oral lavage with polyethylene glycol reduces microbial colonization in the
      gastrointestinal tract of broilers.
AB  - Oral lavage of 7-wk-old broiler chickens with polyethylene glycol (PEG) was
      conducted to induce rapid evacuation of the gastro-intestinal tract (GIT) before
      processing. Three groups of birds were fed ad libitum (FF), subjected to feed
      withdrawal 12 h before processing (FW), or received 115 mL of PEG by oral lavage
      3 h before processing (PEG(L)). The crop, a section of small intestine, and the
      right cecum were aseptically collected for determination of contents and Gram
      negative bacilli (GNB) counts. The PEG(L) effectively cleansed the upper GIT and
      intestine of treated birds within 3 h before processing. However, the ceca were
      not completely empty for all the birds subjected to PEG(L). The PEG(L) group had
      a significantly lower crop and cecal GNB concentrations than the FW group. Birds
      on FW and PEG(L) treatments had significantly lower GNB concentrations in the
      small intestine than FF birds. Polyethylene glycol resulted in complete
      evacuation of the upper GIT, as well as the intestine, within 3 h of use, and
      significantly reduced GNB concentrations.

PMID- 11989761
TI  - Increase of gamma-glutamyl-beta-alanyl-histidine isopeptide in the macromolecular
      fraction of model chicken extract during heating and distribution in commercial
      chicken extracts.
AB  - Changes in the amino acid composition and contents of gamma-glutamyl-beta-alanyl
      histidine isopeptide in the macromolecular fraction were measured during heating
      of chicken extract. Increases of histidine, 1-methylhistidine, and beta-alanine
      were observed, suggesting that carnosine and anserine were incorporated into the
      macromolecular fraction. The increase of gamma-glutamyl-beta-alanylhistidine
      isopeptide in the macromolecular fraction of chicken extract was also observed
      during the heating process. Furthermore, measurement of gamma-glutamyl-beta
      alanylhistidine isopeptide in commercial chicken extract showed that all kinds of
      chicken extract contained the above isopeptide (from 0.09 to 0.31 micromol/g DM
      in the macromolecular fraction). These results suggest that the formation of
      gamma-glutamyl-beta-alanyl-histidine and related isopeptides occur during heating
      of chicken extract.

PMID- 11989762
TI  - Response of spring rape (Brassica napus var. oleifera L.) to inoculation with
      plant growth promoting rhizobacteria containing 1-aminocyclopropane-1-carboxylate
      deaminase depends on nutrient status of the plant.
AB  - Responses of rape (Brassica napus var. oleifera L.) to inoculation with plant
      growth promoting rhizobacteria, Pseudomonas putida Am2, Pseudomonas putida Bm3,
      Alcaligenes xylosoxidans Cm4, and Pseudomonas sp. Dp2, containing 1
      aminocyclopropane-l-carboxylate (ACC) deaminase were studied using growth pouch
      and soil cultures. In growth pouch culture, the bacteria significantly increased
      root elongation of phosphorus-sufficient seedlings, whereas root elongation of
      phosphorus-deficient seedlings was not affected or was even inhibited by the
      bacteria. Bacterial stimulation of root elongation of phosphorus-sufficient
      seedlings was eliminated in the presence of a high ammonia concentration (1 mM)
      in the nutrient solution. Bacterial effects on root elongation of potassium
      deficient and potassium-sufficient seedlings were similar. The bacteria also
      decreased inorganic phosphate content in shoots of potassium- and phosphorus
      sufficient seedlings, reduced ethylene production by phosphorus-sufficient
      seedlings, and inhibited development of root hairs. The effects of treatment with
      Ag+, a chemical inhibitor of plant ethylene production, on root elongation,
      ethylene evolution, and root hair formation were similar to bacterial treatments.
      The number of bacteria on the roots of phosphorus-deficient seedlings was not
      limited by phosphorus deficiency. In pot experiments with soil culture,
      inoculation of seeds with bacteria and treatment with aminoethoxyvinylglycine, an
      inhibitor of ethylene biosynthesis in plants, increased root and (or) shoot
      biomass of rape plants. Stimulation of plant growth caused by the bacteria was
      often associated with a decrease in the content of nutrients, such as P, K, S,
      Mo, and Ba, in shoots, depending on the strain used. The results obtained show
      that the growth-promoting effects of ACC-utilizing rhizobacteria depend
      significantly on the nutrient status of the plant.

PMID- 11989763
TI  - Biotransformation of waste lignin products by the soil-inhabiting yeast
      Trichosporon pullulans.
AB  - In this study the biotransformation of lignin by-products of beechwood pulping
      with a soil-inhabiting yeast strain of Trichosporon pullulans was examined. The
      structural and molecular changes in the lignin during a cultivation process were
      determined by 13C NMR spectroscopy and gel permeation chromatography analysis,
      which confirmed the ability of the yeast strain tested to biodegrade lignin.
      Enzymatic analysis showed the presence of lignin peroxidase and Mn(II) peroxidase
      in the culture supernatant. The ligninolytic activity of both enzymes increased
      under carbon-depleted conditions. This observation is particularly important in
      the biodegradation of recalcitrant lignins in soil.

PMID- 11989764
TI  - The relative ability of fungi from Sphagnum fuscum to decompose selected carbon
      substrates.
AB  - Nine species from a suite of 55 microfungi isolated from living and decomposing
      Sphagnum fuscum were selected for studies of in vitro decomposition of tannic
      acid, cellulose, and starch. In vitro decomposition of S. fuscum plants and
      spruce wood chips was also examined. Oidiodendron maius and Oidiodendron
      scytaloides degraded tannic acid, giving a positive reaction for polyphenol
      oxidases. Most taxa degraded cellulose and starch via the synthesis of cellulases
      and amylase, respectively. Mass losses of spruce wood chips generally exceeded
      those of S. fuscum. A basidiomycete, similar to Bjerkandera adusta, caused the
      greatest mass losses in spruce wood chips (10.2%), while O. scytaloides caused
      the smallest mass losses (3.4%) after 8 weeks. For S. fuscum, Sordaria fimicola
      caused the greatest (5.1%) and Mucor hiemalis the smallest (0.1%) mass losses
      after 8 weeks. Filamentous microfungi have considerable potential to decompose a
      variety of carbon substrates of bryophilous residues in peatlands.

PMID- 11989765
TI  - Purification and characterization of a glucoamylase secreted by the plant
      pathogen Scierotinia sclerotiorum.
AB  - Among the lytic enzymes secreted by the phytopathogen fungus Sclerotinia
      sclerotiorum, a starch-degrading enzyme has been isolated and characterized. This
      glycoprotein of 72 kDa is composed of several isoforms ranging from pI 4.8 to
      5.4. The enzymatic parameters have been determined. Specificity studies together
      with the analysis of the reaction products show that it is an alpha-1,4
      glucanohydrolase. This result is also corroborated by the analysis of the N
      terminal and two inner amino acids sequences that are very similar to fungal
      glucoamylase genes or enzymes so far sequenced.

PMID- 11989766
TI  - Hydrolytic enzymes and antifungal compounds produced by Tilletiopsis species,
      phyllosphere yeasts that are antagonists of powdery mildew fungi.
AB  - Isolates of five species of the yeast-like fungus Tilletiopsis Derx (Tilletiopsis
      albescens Gokhale, Tilletiopsis fulvescens Gokhale, Tilletiopsis minor Nyland,
      Tilletiopsis pallescens Gokhale, and Tilletiopsis washingtonensis Nyland) were
      screened for exo- and endo--beta-1,3-glucanase and chitinase production in a
      liquid broth used to produce inoculum for biological control studies. There were
      significant differences among the species, and highest overall enzyme activity
      was present in T albescens and T. pallescens and lowest in T. washingtonensis. A
      time-course study of beta-1,3-glucanase and chitinase production in T pallescens
      ATCC 96155 in broth culture with 2.5% glucose as the carbon source showed that
      enzyme activity gradually increased over a 3- to 21-day period. Maximum enzyme
      activity was found between pH 4.0 and 5.0. SDS-PAGE of beta-1,3-glucanase
      isozymes revealed a range of molecular masses from 18 to 29 kDa. Five isozymes
      were present in both T albescens and T. pallescens and two in T washingtonensis.
      Antifungal compounds were also detected in ethyl acetate extracts of culture
      filtrates of T. pallescens ATCC 96155 after 6 days of incubation, while no
      activity was detected at 14 days. One active fraction was selected following
      fractionation and preparative chromatography and was bioassayed against
      Podosphaera (sect. Sphaerotheca) xanthii (Castagne) U. Braun & N. Shishkoff and a
      number of other fungi. A concentration of 130 microg/mL inhibited germ tube
      development in P. xanthii, and mildew spores appeared plasmolyzed. Other fungi
      were inhibited at higher concentrations. Collapse of hyphae and conidiophores was
      also observed on mildewed leaves treated with the active fraction. Proton NMR
      analysis indicated that the inhibitory compound was a fatty acid ester. In 3- to
      6-day-old cultures of T pallescens ATCC 96155 demonstrating biological control
      activity, antifungal compound production may have a primary role in restricting
      growth of mildew fungi and other competitors when applied to leaves.

PMID- 11989767
TI  - Isolation of plant-growth-promoting Bacillus strains from soybean root nodules.
AB  - Endophytic bacteria reside within plant tissues and have often been found to
      promote plant growth. Fourteen strains of putative endophytic bacteria, not
      including endosymbiotic Bradyrhizobium strains, were isolated from surface
      sterilized soybean (Glycine max. (L.) Merr.) root nodules. These isolates were
      designated as non-Bradyrhizobium endophytic bacteria (NEB). Three isolates (NEB4,
      NEB5, and NEB17) were found to increase soybean weight when plants were co
      inoculated with one of the isolates and Bradyrhizobium japonicum under nitrogen
      free conditions, compared with plants inoculated with B. japonicum alone. In the
      absence of B. japonicum, these isolates neither nodulated soybean, nor did they
      affect soybean growth. All three isolates were Gram-positive spore-forming rods.
      While Biolog tests indicated that the three isolates belonged to the genus
      Bacillus, it was not possible to determine the species. Phylogenetic analysis of
      16S rRNA gene hypervariant region sequences demonstrated that both NEB4 and NEB5
      are Bacillus subtilis strains, and that NEB17 is a Bacillus thuringiensis strain.

PMID- 11989768
TI  - Effect of different carbon sources and cold shock on protein synthesis by a
      psychrotrophic Acinetobacter sp.
AB  - The induction of proteins after a 25 to 5 degrees C cold shock in the
      psychrotrophic Acinetobacter HH1-l was examined using two-dimensional
      polyacrylamide gel electrophoresis. In addition, effects of various carbon
      sources (acetate, Tween 80, and olive oil) on protein synthesis after cold shock
      were assessed. HH1-1 responded to cold shock by synthesizing both cold shock
      proteins (csps) and cold acclimation proteins (caps). The synthesis of two csps
      (89 and 18) was increased 2 h after cold shock by the cells, regardless of the
      carbon source provided. An additional csp (csp 12), with an estimated molecular
      mass of 12 kDa, was observed in cells grown in olive oil only. Csp 12 was also
      synthesized when cells were incubated at 30 degrees C, suggesting that this
      protein may serve as a general stress protein. In addition to csps, caps were
      observed post cold shock at 72 h in acetate-grown cells and at 140 h in cells
      grown in Tween 80 and olive oil. Induction of cold-acclimated periplasmic
      proteins was observed for cells grown in olive oil only, suggesting cells grown
      in olive oil may be stressed by low temperatures to a greater extent than cells
      grown in either acetate or Tween 80.

PMID- 11989769
TI  - Detecting structural and functional differences in activated sludge bacterial
      communities originating from laboratory treatment of elementally and totally
      chlorine-free bleaching effluents.
AB  - The ability to differentiate functional and structural diversity of bacterial
      communities present in activated sludges adapted to elementally (ECF) and totally
      (TCF) chlorine-free bleaching effluents was evaluated. Community function was
      evaluated through substrate utilization patterns in BiologGN microplates, and
      taxonomic structure was evaluated by fluorescent in situ hybridization using
      probes targeting the Eubacteria; the alpha, beta, and gamma subclasses of the
      Proteobacteria; and gram-positive bacteria with high GC content. Over 6-week
      sampling periods, ECF-and TCF-adapted sludge bacterial communities presented
      reproducible substrate utilization patterns that through principal components
      (PCs) analysis, separated the ECF samples from the TCF samples. Application of
      the fluorescent in situ hybridization technique was complicated by the intense
      autofluorescence of the bleaching effluent sludge samples that interfered with
      detection of specific hybridization signals. The most notable difference in
      community structure detected using the chosen set of probes was the relatively
      greater proportion of cells of the alpha subclass in TCF sludge (27%) than in ECF
      sludge (6%). Nonspecific hybridization with beta and gamma probes was relatively
      high, but both sludges appeared to have similar proportions of cells of the beta
      (20-22%) and gamma (11-12%) subclasses. The two sludges presented relatively few
      gram-positive cells with high GC content (<0.2% of eubacterial counts).
      Differences in both metabolic potential and taxonomic structure of the microbial
      communities in the ECF- and TCF-activated sludges were detected. The kinetics of
      the development of these differences in treatment plants and their relationships
      with treatment efficiency and production process conditions should now be
      evaluated.

PMID- 11989770
TI  - Long-term survival and germination of Bacillus thuringiensis var. kurstaki in a
      field trial.
AB  - Long-term survival, dispersal, and germination of Bacillus thuringiensis var.
      kurstaki DMU67R has been investigated in a field trial. An experimental cabbage
      plot was sprayed with DMU67R in 1993 and allowed to lie fallow since. The
      investigations reported here were carried out from 1997 to 2000 in this plot.
      High persistence of DMU67R for 7 years in the bulk soil of the plot has been
      demonstrated. The numbers have not significantly reduced since 1994, stabilizing
      around 6.6 x 10(2) cfu/g from 1996 to 2000. Horizontal dispersal of DMU67R in the
      1994-1999 period was limited. Vertical dispersal occurred from 1994 to 1999, as
      77% of the population of DMU67R occurred in the 0-2 cm layer in 1994, while only
      22% of the population was found there in 1999. Most of the population in 1999 was
      present homogeneously in the upper 6 cm of the soil profile. Germination, as
      evidenced by the ratio of DMU67R cfu before and after heat treatment, was not
      observed in the bulk soil. However, in the rhizospheres of dandelion (Taraxacum
      officinalis) and quackgrass (Agropyron repens), 40 and 50% of DMU67R was present
      as vegetative germinated cells, respectively. No germination occurred in the
      rhizosphere of red fescue (Festuca rubra). The material from the gut of the
      earthworm species Lumbricus rubellus, Lumbricus terrestris, and Apporrectodea
      caliginosa and from a tipulid larvae from the plot also contained vegetative
      cells of DMU67R. Further investigations of A. caliginosa showed that germination
      seemed to be restricted to the gut and that sporulation occurred after
      defecation. The germination of DMU67R in rhizospheres and in the gut of nontarget
      invertebrates suggests that survival in the soil of B. thuringiensis is a dynamic
      process involving germination, cell divisions, and sporulation in specific
      microhabitats.

PMID- 11989771
TI  - Larvicidal toxins from Bacillus thuringiensis subspp. kurstaki, morrisoni (strain
      tenebrionis), and israelensis have no microbicidal or microbiostatic activity
      against selected bacteria, fungi, and algae in vitro.
AB  - The insecticidal toxins from Bacillus thuringiensis subspp. kurstaki
      (antilepidopteran), morrisoni strain tenebrionis (anticoleopteran), and
      israelensis (antidipteran) did not affect the growth of a variety of bacteria (8
      gram-negative, 5 gram-positive, and a cyanobacterium), fungi (2 Zygomycetes, 1
      Ascomycete, 2 Deuteromycetes, and 2 yeasts), and algae (primarily green and
      diatoms) in pure and mixed culture, as determined by dilution, disk-diffusion,
      and sporulation assays with purified free and clay-bound toxins. The insecticidal
      crystal proteins from B. thuringiensis subspp. kurstaki and israelensis had no
      antibiotic effect on various gram-positive bacteria.

PMID- 11989772
TI  - Increased ratio of mitochondrial rDNA to cytoplasmic rDNA during zoosporic and
      germinating cyst stages of the life cycle of Phytophthora infestans (Mont.) de
      Bary.
AB  - A differential RNA display approach was used to study the gene expression in
      zoospores (Z) and germinating cysts (GC) of the late blight pathogen Phytophthora
      infestans. Four differentially amplified cDNAs were selected and cloned. The
      clone pGPiZ0.5 showed a 2.7-kb transcript highly expressed in Z. A BLAST search
      revealed an almost full sequence homology (98%) to the P. infestans mitochondrial
      large subunit rRNA. Northern blot analysis showed a twofold accumulation of the
      mitochondrial rRNA (mit rRNA) in Z compared with that of GC and mycelia of P.
      infestans. The high level of mit rRNA in Z might reflect an increased number of
      gene copies, an increased rDNA transcription rate, or both. Dot blot experiments
      indicated that the amount of mitochondrial rDNA (mit rDNA) relative to
      cytoplasmic rDNA is twofold higher in Z and GC than in mycelia. This relatively
      elevated mit rDNA could explain the high level of mit rRNA in the zoosporic
      phase. On the contrary, GC conserves the mit rDNA content, but the level of mit
      rRNA drops to 50% that of Z. The data are consistent with a very active
      mitochondrial protein synthesis during zoosporic phase, followed by a rapid down
      regulation of mitochondrial activity during cyst formation.

PMID- 11989773
TI  - Evaluation of two commercial methods for the detection of Listeria sp. and
      Listeria monocytogenes in a chicken nugget processing plant.
AB  - This study measures the detection performances of two rapid test systems
      (Listeria Rapid Test Clearview and Bax system) for the screening of Listeria sp.
      and Listeria monocytogenes, respectively. A total of 413 samples from different
      sources (product from (i) different stages of processing, (ii) different
      environments, and (iii) different food handlers), collected from a chicken nugget
      processing plant, were analysed by both rapid methods and a cultural method
      consisting of pre-enrichment, enrichment, and isolation onto selective agars
      (PALCAM, LPM, and HCLA). Overall, results showed an excellent correlation between
      data obtained using Clearview and the cultural method, with Clearview presenting
      an efficiency of 99%. Bax showed a lower correlation using the cultural method,
      with an efficiency of 71.1%. The type of sample did not affect the efficiency of
      Clearview, which varied from 98.1% for product samples to 100% for environmental
      and food handler samples, while for Bax it had a marked influence. Efficiency of
      Bax varied from as high as 100% for food handlers to 37.9% for product samples.

PMID- 11989774
TI  - Memoires, the development of Scandinavian electron microscopy.

PMID- 11989776
TI  - Skeletal muscle microvascular alterations in euthyroid and hypothyroid patients
      with autoimmune thyroid disease.
AB  - An electron microscopic study of skeletal muscle biopsies from euthyroid and
      hypothyroid patients with autoimmune thyroid disease (ATD) showed the existence
      of capillary alterations and a mononuclear cell infiltrate. Microvascular
      abnormalities included thickening and lamination of basement membrane,
      endothelial proliferation with progressive lumen occlusion, and hypertrophied
      pericytes. Capillary degeneration was also observed. Macrophages, and scarce
      lymphocytes and mast cells formed the cell infiltrate. This pathological picture
      is similar to that found in the muscular compromise of other autoimmune diseases,
      particularly Graves' hyperthyroidism. This study shows that patients with ATD may
      have skeletal muscle capillary abnormalities that could probably be related to
      autoimmunity and are independent of thyroid functional status.

PMID- 11989775
TI  - Ultrastructural study of expression of adhesion molecules between blood monocytes
      and alveolar macrophages from patients with pulmonary sarcoidosis.
AB  - Pulmonary sarcoidosis is a chronic inflammatory disorder characterized by the
      presence of activated T cells and alveolar macrophages at sites of inflammation.
      These cells are recovered from bronchoalveolar lavage (BAL) from sarcoid patients
      in order to evaluate the expression of various markers on cell surfaces that
      should determine the diagnosis in sarcoidosis. In this work we compared the
      expression of VLA-4, VLA-5, Mac-1, ICAM-1 and VCAM- 1 adhesion molecules, at
      ultrastructural level, between blood monocytes and alveolar macrophages obtained
      from BAL, from patients with pulmonary sarcoidosis. Cells obtained from blood and
      BAL were fixed, embedded in LRWhite and then ultrathin sections were incubated
      with monoclonal antibodies against VLA-4, VLA-5, Mac-1, ICAM-1 and VCAM-1. The
      results showed a more evident labelling of all adhesion molecules on alveolar
      macrophages when compared to blood monocytes. The labelling was seen at cell
      surface, at cytoplasm and small vacuoles. The differences on adhesion molecule
      distributions from blood monocytes to alveolar macrophages suggest that changes
      in the expression of these molecules occur during pulmonary inflammatory
      response. Lymphocytes from BAL or blood had a weak label for these molecules.

PMID- 11989777
TI  - Division and motility of mitochondria in sea urchin embryogenesis.
AB  - The influence of actin and tubulin cytoskeletons on the shape, division and on
      intracellular motility of mitochondria was studied in eggs and embryos of the sea
      urchin Paracentrotus lividus. Depolymerization of actin filaments and
      microtubules was induced by specific inhibitors as cytochalasin D (CytD) and
      colcemid respectively. The quantitative analysis of the mitochondrial population
      shows that: 1) the chondriome of an egg consists of numerous (about 15,000)
      discrete mitochondrial clusters uniformly distributed throughout the cytoplasm,
      each cluster containing 10 to 20 mitochondria of spherical or rod-like shape; 2)
      fertilization induces cluster break-down and mitochondrial division within 15 min
      after insemination; at 100 min after fertilization mitochondria become evenly
      distributed throughout the cytoplasm and the population of mitochondria doubles;
      3) in embryos obtained from eggs inseminated after treatment with CytD clusters
      break-down and mitochondriokinesis are blocked; 4) when added 15 min after
      insemination, CytD uncouples coordinated invagination of outer and inner
      membranes in dividing mitochondria thus bringing about abnormal
      mitochondriokinesis; 5) the treatment of the eggs with colcemid does not affect
      the normal embryonic mitochondriokinesis.

PMID- 11989778
TI  - Ultrastructural evaluation of the effects of the contrast media on the rat
      kidney.
AB  - In this study, the ultrastructural observations in rat kidneys were studied 2, 24
      and 48 h after intravenous injection of 1, 3 and 9 g iodine per kg body of
      ioxaglate and iohexol. The effect of the contrast media was mainly on the
      proximal convoluted tubule cells, the presence of vacuoles containing granular
      and membranous structures was a striking feature. In the distal convoluted
      tubular cells, pycnotic nuclei and cytoplasmic bulges toward the lumen were
      observed. In some glomeruli, membranous structures in cytoplasm of podocytes and
      thickening of glomerular basal membrane were seen. Values of biochemical analysis
      were slightly higher especially at high doses in experimental groups when
      compared to the control. The results suggest that iohexol causes more
      degeneration than ioxaglate. Not only proximal convoluted tubule cells but also
      the other parts of the nephron were affected by contrast media.

PMID- 11989779
TI  - Morphology of the seminal vesicle of Calomys callosus submitted to experimental
      chronic alcoholism.
AB  - The objective of the present study was to assess the possible toxic effects of
      chronic alcohol ingestion on the ultrastructure of the lining epithelium of the
      seminal vesicle of the rodent Calomys callosus, in order to contribute to the
      understanding of the consequences of alcohol abuse for the morphology of the male
      reproductive apparatus. Twenty six adult animals aged three months were divided
      into two experimental groups. The control group received a solid diet (Purina
      chow) and tap water, and the alcoholic group received the same solid diet and
      ethanol P.A. diluted 20% in water (v/v). After 210 days of treatment, all animals
      were anaesthetised, weighed and sacrificed. At the end of treatment, mean body
      and seminal vesicle weight did not differ between control and alcoholic animals.
      The epithelial cells of the alcoholic group showed many alterations such as the
      presence of lipid droplets of different sizes, nuclei with increased peripheral
      chromatin and greater electrondensity, megamitochondria, and intense dilatation
      of the cisterns of the granular endoplasmic reticulum. It was concluded that 20%
      ethanol provokes marked ultrastructural lesions in the seminal vesicle.

PMID- 11989780
TI  - Differential distribution of the fibres of the collagenous and elastic systems
      and of glycosaminoglycans in the rat pubic joint.
AB  - The pubic joint of male and female rats was studied at the light- and electron
      microscopical levels using methods that selectively disclose the extracellular
      matrix fibres and glycosaminoglycans. The interpubic tissue showed no difference
      between sexes (including pregnant and intrapartum females). The medial ends of
      the pubic bones were covered by articular caps of hyaline cartilage that blended
      in the midline. The whole articular cartilage was covered dorsally and ventrally
      (as well as craneally and caudally) by a typical perichondrium. The differential
      distribution of the fibres of the collagenous and elastic systems in the pubic
      joint agreed with the results reported in the literature for other rat
      cartilages. Collagen fibres, composed mainly of type-I collagen, were localised
      to the fibrous perichondrium and bone. Type-II collagen was localised to the
      central nucleus of hyaline cartilage, whereas reticulin fibres (rich in type-III
      collagen) were found in the adventitial loose connective tissue adherent to the
      most superficial layer of the perichondrium. The central nucleus of hyaline
      cartilage possessed the two types of elastic-related fibres: elaunin fibres were
      localised mainly to the chondrogenic layer of the perichondrium, whereas oxytalan
      fibres were found in the matrix that surrounded the chondrocytes. The bulk of the
      glycosaminoglycans present in the pubic joint cartilage corresponded to
      hyaluronic acid and chondroitin sulphate. The propriety of classification of the
      rat pubic joint as a true synchondrosis (instead of symphysis), and the fact that
      the unaltered pelvis of the rat seems to be adequate for normal parturition, are
      discussed.

PMID- 11989781
TI  - Quantification of macrophage aggregates in the liver of Mugil cephalus.
AB  - Macrophages are involved in the recycling, storage and detoxification of cellular
      debris/waste products and exogenous substances their presence is quite normal. An
      accumulation of these cells, however, can be the sign of an alteration. A
      quantification of the surface area occupied by macrophage aggregates (1.3 to
      21.5%) in Mugil cephalus suggests a possible environmental stress for the
      specimens examined.

PMID- 11989782
TI  - Cytotoxic effects against HeLa cells of polysaccharides from seaweeds.
AB  - Polysaccharides extracted from several red and brown seaweeds growing along the
      South American coasts were evaluated regarding their cytotoxic effects against
      HeLa cells. Sulfated galactans were isolated and purified from the red algae
      Bostrychia montagnei (BHW and B4 fractions, 17 and 22% SO3Na, respectively) and
      Porphyra columbina (PC75 fraction, 15.6% SO3Na). At maximum concentration of 80
      microg/mL, these fractions promoted atypical mitoses in HeLa cells, presence of
      atypical nuclei and blebs. Alginic acid (160.0 microg/mL) isolated from the brown
      seaweed Laminaria brasiliensis (molar ratio M/G 1.2) and its M and G blocks (40.0
      microg/mL; DP = 20), promoted similar morphologic alterations besides the
      presence of acidophilic material in the cellular cytoplasm and occurrence of
      multinuclear cells present in the monolayer. The polysaccharide fraction SF
      isolated from the brown seaweed Sargassum stenophyllum containing mainly fucose
      and presenting molar ratio of sulfate/sugar 1.9, promoted very accentuated
      morphologic modifications in HeLa cells at low concentrations. SF (2.5 microg/mL)
      caused significant alterations in the cellular morphology and reduction of the
      growth, such effects being dose dependent. At 40.0 microg/mL, accentuated
      decrease of the number of mitosis illustrations accompanied by an increase in the
      number of condensed cells, atypical nuclei, number of clusters and blebs. These
      results demonstrated that among the anionic polysaccharides tested, the sulfated
      fucans were those which caused greater cytotoxic effects in HeLa cells.

PMID- 11989783
TI  - Cloning and expression pattern of a spermatogenesis-related gene, BEX1, mapped to
      chromosome Xq22.
AB  - Through screening a human fetal brain cDNA library, a cDNA similar to the mouse
      Bex1 was isolated. This new gene was named brain expressed X-linked protein 1
      (BEX1). Northern blot analysis revealed a 1.0 kb transcript highly expressed in
      brain, pancreas, testis, and ovary, with lower levels present in heart, placenta,
      liver, kidney, spleen, thymus, prostate, small intestine, colon (no mucus),
      thyroid, spinal cord, and adrenal gland. No hybridization signal was seen in
      lung, skeletal muscle, peripheral blood leukocyte, stomach, lymph node, trachea,
      and bone marrow. The BEX1 gene was localized to chromosome band Xq22 between
      markers between DXS990 and DXS1059 by screening Stanford radiation hybrid G3
      panels. In situ hybridization of mouse testis using BEX1 as a probe detected the
      signal in the pachytene spermatocytes and spermatids but not in spermatogonia.
      Furthermore, it was not detected at 6, 9, and 12 days postpartum, was present in
      low amount on Days 15 and 18 and its expression increased sharply after the
      initiation of puberty (about 21 days) in mouse testis.

PMID- 11989784
TI  - Differential effects of the KitW mutation with other Kit allelic combinations on
      male sterility among inter- or intrasubspecific hybrids in mice.
AB  - The combination of the KitW mutation and KitS allele from Mus spretus leads to
      male hybrid sterility. The effects of other combinations between KitW and KitM
      from Mus m. molossinus or KitN from Mus m. musculus on male reproductive ability
      were examined in this study. The KitW/KitM and KitW/KitN males were fertile and
      showed the normal pattern of spermatogenesis in most seminiferous tubules. There
      were two amino acid substitutions in the protein deduced from the cDNA sequence
      coded by the KitM allele sequence and three in the KitN allele compared with the
      protein from the + Kit allele of C57BL mice. These amino acid exchanges had no
      effect on the fertility of KitW/KitM and KitW/KitN males. Therefore, comparing
      the sequence data from cDNA coded by KitM and KitN alleles with that for the KitS
      allele, we concluded that one or more amino acid exchanges in the extracellular
      domain would be the cause of male hybrid sterility in the KitW/KitS combination;
      these substitutions are Phe to Ser at position 72, Thr to Ala at 95, Ser to Arg
      at 101, Leu to Pro at 123, and Ile to Met at 1303.

PMID- 11989785
TI  - Apolipoprotein C polymorphism in sheep: allele frequencies and association with
      plasma lipid and lipoprotein levels.
AB  - The genetic polymorphism of apolipoprotein C in normal plasma of four European
      sheep breeds (Suffolk, Corriedale, Cheviot, and Finn) was first detected using
      one-dimensional polyacrylamide gel isoelectric focusing (pH 2.5-5.0) followed by
      immunoblotting with antihuman apolipoprotein CII antibody. Six phenotypes (1-1, 2
      1, 2-2, 3-1, 3-2, and 3-3) were identified in the 4.3-4.8 pH range, consisting of
      the combination of three isoform groups. On the basis of family and population
      data, these phenotypes were controlled autosomally by three codominant alleles,
      designated APOC*1, APOC*2, and APOC*3, the first being the most common allele.
      The frequency distributions of these alleles were similar between the Suffolk and
      Corriedale sheep, and between the Cheviot and Finn sheep. The former breeds had a
      significantly lower APOC*2 frequency than the latter breeds (P < 0.001). The mean
      plasma total-, HDL- and LDL-cholesterol levels of type 3-1 animals were
      significantly higher compared to type 1-1 animals in the Suffolk sheep (P < or =
      0.04). However these differences were not seen in the Corriedale sheep.

PMID- 11989786
TI  - Length polymorphism of thymidylate synthase regulatory region in Chinese
      populations and evolution of the novel alleles.
AB  - The tandemly repeated 28-bp sequence in the 5'-terminal regulatory region of
      human thymidylate synthase (TSER), which has been reported to be polymorphic in
      different populations, was surveyed in 668 Chinese from 9 Han groups, 8 ethnic
      populations, and 36 individuals representing a three-generation pedigree.
      Amplified fragments were separated by electrophoresis on 4% agarose gel. In
      addition to the reported double and triple repeats of the 28-bp sequence in TSER,
      we also detected a novel quintuple repeat in this region. The transient
      expression activity of TSER with the quintuple repeat is almost the same as that
      of the reported TSER with the triple repeat. All three alleles of the repeat type
      (2, 3, and 5) were further confined by sequencing. The frequencies of the TSER
      allele 2 and 3 were 18.82 and 81% in totally unrelated Chinese samples,
      respectively, while the frequency of allele 3 was variable in different Chinese
      populations with a range from 62 to 95%. On the basis of the sequences of the
      different alleles, the existence of the tandem repeats in each allele might be
      explained by slipped-strand mispairing during DNA replication.

PMID- 11989787
TI  - Noncryogenic preservation of mammalian tissues for DNA extraction: an assessment
      of storage methods.
AB  - Reliable field methods for the storage of tissues to be used for DNA extraction
      and amplification are critical to many studies employing molecular techniques.
      Protection from DNA degradation was compared among three commonly used methods of
      noncryogenic storage of tissues over a time scale of 2 years. All three methods
      prevented DNA degradation during storage for at least 6 months. DMSO (dimethyl
      sulfoxide)-salt solution provided the best protection from DNA degradation of
      tissues stored for up to 2 years. High molecular weight DNA was recovered from
      lysis buffer in which tissue was stored for 2 years, however, moderate amounts of
      degraded DNA was also present. High molecular weight DNA was recovered from
      tissues stored in ethanol for 2 years, however the yield was relatively small
      compared to the other two noncryogenic storage techniques. Much of the DNA
      degradation in ethanol preserved tissues appeared to occur during the extraction
      procedure and can be reduced by soaking the tissue in lysis buffer for a few
      hours prior to beginning the extraction. The yield of PCR products was greatest
      from DNA extracted from DMSO-salt solution preserved tissues, whereas DNA from
      tissues stored in either lysis buffer or ethanol produced lower yields.

PMID- 11989788
TI  - Diversity analysis of Indian tetraploid wheat using intersimple sequence repeat
      markers reveals their superiority over random amplified polymorphic DNA markers.

PMID- 11989789
TI  - Early vascular permeability in murine experimental peritonitis is co-mediated by
      resident peritoneal macrophages and mast cells: crucial involvement of macrophage
      derived cysteinyl-leukotrienes.
AB  - The initial phase of zymosan-induced peritonitis involves an increase of vascular
      permeability (peak at 30 min) that is correlated with high levels of vasoactive
      eicosanoids, namely, prostaglandins (PGI2 and PGE2) of cyclooxygenase-1 origin
      (as estimated by RT-PCR) and cysteinyl-leukotrienes. Previously, we showed that
      the increase of vascular permeability can be attributed only partially to mast
      cells and their histamine, as seen in mast cell-deficient WBB6F1-W/Wv mice. Thus
      we aimed to identify the major cellular source(s) that mediate vasopermeability,
      as well as particular vasoactive mediators operating in this model. For this
      purpose, some mice were selectively depleted of either peritoneal macrophages or
      mast cells, and/or they were treated with several pharmacologic inhibitors of
      cyclooxygenase- and lipoxygenase-metabolic pathways. More-over, macrophage
      depleted mast cell-deficient WBB6F1-W/Wv mice and their controls (+/+) were used.
      The macrophage depletion always caused a profound decrease of both vascular
      permeability and lipid-mediator levels, which was particularly pronounced for
      leukotrienes, whereas the effects of mast-cell depletion were less severe. The
      macrophage/mast-cell co-mediation of vasopermeability was also revealed in
      thioglycolate-induced peritonitis, as well as the macrophage origin of cysteinyl
      leukotrienes. Taken together, these findings demonstrate that the resident
      peritoneal macrophages are in fact the main contributors to the vasopermeability
      at the early stages of zymosan-induced peritonitis.

PMID- 11989790
TI  - Inflammatory cytokines mediate C-C (monocyte chemotactic protein 1) and C-X-C
      (interleukin 8) chemokine expression in human pleural fibroblasts.
AB  - Current knowledge implicates pleural mesothelial cells as mainly responsible for
      inflammatory responses in the pleural space. However, a vast body of recent
      evidence underscores the important role of fibroblasts in the process of
      inflammation in several types of tissues. We hypothesize that HPFBs (human
      pleural fibroblasts) play an important role in pleural responses and also when
      activated by bacterial endotoxin LPS (lipopolysaccharide), IL-1 beta (interleukin
      1 beta), or TNF-alpha (tumor necrosis factor-alpha) release of C-C and C-X-C
      chemokines-specifically, MCP-1 and IL-8. Our results show that pleural fluid
      isolated human fibroblasts release IL-8 and MCP-1 upon stimulation with IL-1
      beta, TNF-alpha, and LPS in both a concentration- and time-dependent manner. RT
      PCR (reverse-transcriptase-polymerase chain reaction) studies have also confirmed
      IL-8- and MCP-1-specific mRNA expression in activated pleural fibroblasts. On the
      time-dependent response curve, IL-8 was found in maximum concentrations at 144
      hr, whereas MCP-1 continued to increase even after 196 hr following stimulation.
      IL-1 beta induced the maximum release of IL-8 (800-fold) and MCP-1 (164-fold), as
      compared to the controls. TNF-alpha induced a 95-fold increase in IL-8 and an 84
      fold increase in MCP-1 levels, as compared to the controls. Collectively, our
      results show that human pleural fibroblasts contribute to the inflammatory
      cascade in the pleural space.

PMID- 11989791
TI  - Inhibition of IL-8-mediated MAPK activation in human neutrophils by beta1
      integrin ligands.
AB  - Chemokine and integrin receptors must work in concert when circulating leukocytes
      mobilize toward a site of tissue inflammation or infection. In a previous study,
      we reported that ligation of the alpha5beta1 integrin with a 120-kDa cell-binding
      fibronectin fragment (120-kDa FN) in suspensions of human polymorphonuclear
      leukocytes (PMNLs) inhibited chemotaxis toward the chemokine called interleukin-8
      (IL-8). Binding of chemokines to their receptors on leukocytes leads to the
      activation of heterotrimeric G proteins that initiate multiple signaling
      cascades, including p38 and p42/p44 mitogen-activated protein kinase (MAPK)
      pathways. In the present study, we examine the potential interaction of beta1
      integrin ligation on chemokine-mediated MAPK signaling in human PMNLs. We
      demonstrate that blockade of the p42/p44 MAPK signaling pathway by the inhibitor
      PD98059 suppresses IL-8-mediated PMNL chemotaxis. Furthermore, when PMNLs are
      pretreated with 120-kDa FN or an activating antibody to beta1 integrins (TS2/16),
      IL-8-mediated phosphorylation of p42/p44 MAPK is also inhibited. In contrast,
      pretreating PMNL with a specific ligand (laminin-1) for the alpha6beta1 integrin
      does not suppress IL-8-mediated phosphorylation of p42/p44 MAPK. These
      observations demonstrate a desensitization of IL-8-mediated p42/p44 MAPK
      signaling in response to ligation of the alpha5beta1 integrin in PMNL. Also, they
      suggest an interplay between integrin and chemokine signaling during PMNL
      migration through the extracellular matrix.

PMID- 11989792
TI  - Effects of Allergina on the treatment of otitis media with effusions.
AB  - The number of pediatric patients with recurrent otitis media with effusions
      (ROMEs) is increasing because of the frequency of recurrence. The herbal
      combination Allergina is used for inflammatory-disease treatment in the Republic
      of Korea; in our study, the patients with ROME were treated with either Allergina
      (11 ears) or antibiotics (13 ears). We analyzed the levels of cytokines in middle
      ear effusions (MEEs) and compared these levels in the Allergina-treated patients
      with those in the antibiotics-treated patients. The mean levels of interleukin
      (IL)-2 and IL-4 in MEEs were significantly higher in the Allergina-treated
      patients than in the antibiotics-treated patients, whereas levels of IL-1beta, IL
      6, IL-8, and tumor necrosis factor (TNF)-alpha in MEEs were significantly lower
      in the Allergina-treated patients than in the antibiotics-treated patients.
      Clinical signs of ROME disappeared markedly after all the patients were given an
      oral administration of Allergina. Our experimental studies provide evidence that
      Allergina may be beneficial in the treatment of ROME by regulating cytokine
      production.

PMID- 11989794
TI  - Synthesis and antimicrobial activity of some novel 2-(p-substituted-phenyl)-5
      substituted-carbonylaminobenzoxazoles.
AB  - A series of 2-(p-substituted-phenyl)-5-substituted-carbonylamino benzoxazole
      derivatives (5-22) was synthesized and their antimicrobial activities determined
      in comparison to several control drugs. The synthesized compounds were tested in
      vitro against Staphylococcus aureus, Streptococcus faecalis and Bacillus subtilis
      as Gram-positive, Pseudomonas aeruginosa and Escherichia coli as Gram-negative
      bacteria and the yeast Candida albicans. Microbiological results showed that the
      compounds possessed a diffuse spectrum of antibacterial activity against these
      microorganisms. Compound 9 which bears a phenylacetamido moiety at position 5 and
      a 4-fluorophenyl group at the 2-position of benzoxazole ring was the most active
      derivative against S. aureus, S. faecalis and P. aeruginosa with a MIC value of
      12.5 microg/ml. Compound 11 provided higher potency than the other tested
      compounds against B. subtilis at a MIC value of 12.5 microg/ml. Compounds 5-22
      showed antifungal activity against C. albicans with MIC values between 50 and
      12.5 microg/ml.

PMID- 11989793
TI  - Muscle proteolysis and weight loss in a neonatal rat model of sepsis syndrome.
AB  - Our hypothesis is that nitrogen loss in septic neonates is caused by increased
      muscle proteolysis. Sprague-Dawley rat pups (P7) were injected intraperitoneally
      with NaCl or 4 mg/kg/BW lipopolysaccharide (LPS) and then sacrificed at 2, 4, 24,
      and 48 hr. Sepsis syndrome was confirmed by elevated serum tumor necrosis factor
      (24.6 ng/mL +/- 18.4 [LPS] and < 1.0 ng/mL [controls]; p < .05). Proteolysis in
      gastrocnemius/soleus muscle was analyzed by quantitation of tissue tyrosine loss.
      The neonatal rats injected with LPS had significant media tyrosine release at 24
      hr compared to the controls (0.39 +/- 0.14 versus 0.25 +/- 0.11 micromol
      tyrosine/g muscle; p < .05). At 48 hr, LPS-induced muscle tyrosine release ceased
      (0.24 +/- 0.04 [control] versus 0.23 +/- 0.03 micromol tyrosine/g muscle [LPS]).
      After 48 hr, gastrocnemius/soleus weight was less in the LPS-injected rats (50.5
      +/- 4.8 to 31.2 +/- 4.0 g; p < .0001). Similar changes were not seen in the
      extensor digitorum longus, suggesting that some muscles were relatively
      preserved. Also, LPS resulted in significant weight loss. We conclude that
      selective muscle proteolysis contributes to nitrogen loss in neonatal sepsis.
      Although proteolysis abates by 48 hr, short-term injury results in significant
      muscle-mass deficit.

PMID- 11989795
TI  - Synthesis and antifungal activity of new N-(1-phenyl-4-carbetoxypyrazol-5-yl)-, N
      (indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides.
AB  - N-(1-Phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2
      iodobenzamides 6, with a Benodanil-like structure, were synthesized by refluxing
      in acetic acid the corresponding benzotriazinones 5 with potassium iodide for 1 h
      in order to study the role on the antifungal activity of the N-substitution with
      an aromatic heterocyclic system on benzamide moiety. Among the tested
      iododerivatives, compounds 6d,f,g,h possess interesting activities toward some
      phytopathogenic fungal strains.

PMID- 11989796
TI  - Aminoderivatives of cycloalkanespirohydantoins: synthesis and biological
      activity.
AB  - 3-Aminocycloalkanespiro-5-hydantoins were synthesized and their biological
      activity was studied. In contrast to hydantoins, these compounds failed to induce
      either anticonvulsive effects in the central nervous system or inhibitory effects
      on cholinergic contractions in the enteric nervous system. However, they exerted
      well pronounced, atropinsensitive, contractile effects on the guinea-pig ileum
      longitudinal muscle preparations. Structure-activity relationships established
      allow the assumption that: (i) the reduction of the ring size in the molecule of
      the spirohydantoins leads to an increase in the potency of the respective
      analogue to induce contractile effect; (ii) the introduction of -NH2 in position
      3 increases the ability of all the compounds studied to exert contractions; (iii)
      the enlargement of the ring leads to: (1) an increase of the degree of
      desensitization of the preparations; and (2) a decrease (except 1a) of the
      potency of the analogues to exert contractile effects.

PMID- 11989797
TI  - Synthesis and calcium channel antagonist activity of nifedipine analogues with
      methylthioimidazole substituent.
AB  - Various diester analogues of nifedipine, in which the orthonitrophenyl group at
      position 4 is replaced by 1-methyl-2-methylthio-5-imidazolyl substituent, were
      synthesized and evaluated as calcium channel antagonists on guinea-pig ileal
      smooth muscle. Nifedipine was used as standard. Comparison of the activities of
      symmetrical esters (3a-e) indicate that increasing the length of alkyl chain in
      C3 and C5 ester substituents increases the antagonist activity and the n-propyl
      ester being preferred (IC50= 2.66 x 10(-9) M). In asymmetrical series (6a-g),
      compound 6g having ethyl and n-butyl ester at C3 and C5 positions of basic
      dihydropyridine structure was found to be the most active (IC50= 1.32 x 10(-9)
      M).

PMID- 11989798
TI  - Synthesis and anticonvulsant activity of some omega-(1H-1-imidazolyl)-N
      phenylalkanoic acid amide derivatives.
AB  - In this study, 15 omega-(1H-imidazol-1-yl)-N-phenylacetamide, propionamide and
      butyramide derivatives having methoxyl, methyl, nitro and chloro in ortho
      position of N-phenyl ring or without any substituent have been realized by two
      step synthesis. Their anticonvulsant activity was determined against seizures
      induced by maximal electroshock (MES). The most active compound in the series was
      2-(1H-imidazol-1-yl)-N-(o-chlorophenyl)acetamide.

PMID- 11989799
TI  - Syntheses, chemical and enzymatic stability of new poly(ethylene glycol)
      acyclovir prodrugs.
AB  - Two known antiherpetic agents, acyclovir and valaciclovir, were coupled with
      activated poly(ethylene glycol). In vitro drug release studies demonstrated the
      conjugates to be stable in buffer solutions at pH 7.4 and 5.5, while only PEG
      valacyclovir2 was stable in a buffer solution at pH 1.2. The ability of the
      macromolecular conjugate to release the free drug was also evaluated in plasma,
      in which the most stable prodrug also proved to be PEG-valacyclovir2. The
      derivatives are degraded in the presence of proteolytic enzyme. The rate of
      hydrolysis was monitored by HPLC-analysis.

PMID- 11989800
TI  - Flow injection spectrophotometric determination of adrenaline in pharmaceutical
      formulations using a solid-phase reactor containing lead(IV) dioxide immobilized
      in a polyester resin.
AB  - A flow injection spectrophotometric procedure is proposed for determining
      adrenaline in pharmaceutical formulations. In this work, the adrenaline in
      acetate buffer reacts with a solid-phase reactor containing lead(IV) dioxide
      immobilized in a polyester resin and the adrenochrome yielded was continuously
      monitored at 486 nm. The analytical curve was linear in the adrenaline
      concentration range from 0.1 to 0.8 mmol l(-1) with a detection limit of 8 x 10(
      3) mmol l(-1). Recoveries of 96.5-105% and relative standard deviation of 0.2%
      for a solution containing 0.4 mmol l(-1) adrenaline (n = 10) were obtained. The
      analytical frequency was 130 determinations per hour and the results obtained for
      adrenaline in pharmaceutical formulations using this procedure and those obtained
      using a pharmacopoeia procedure are in agreement at the 95% confidence level.

PMID- 11989801
TI  - Erythro- and threo-2-hydroxynonyl substituted 2-phenyladenines and 2-phenyl-8
      azaadenines: ligands for A1 adenosine receptors and adenosine deaminase.
AB  - erythro-2-Phenyl-9-(2-hydroxy-3-nonyl)adenine and its 8-aza analog were prepared
      and showed a very high inhibitory activity towards adenosine deaminase (ADA),
      with Ki 0.55 and 1.67 nM, respectively, and high affinity for A1 adenosine
      receptors, with Ki 28 and 2.8 nM, respectively. To increase affinity for A1
      receptors we introduced a substituent on the N6 position such as alkyl or
      cycloalkyl groups, which are present in effective agonists or antagonists.
      Furthermore, for some compounds, we prepared the two diastereoisomers erythro and
      threo to verify whether the binding with A1 receptors is stereoselective, as in
      ADA. Results show that some of the synthesised compounds are good inhibitors for
      ADA and good ligands for A1, and the erythro diastereoisomers are more active
      than the threo ones. The experimental evidence allows us to hypothesise some
      similarity in the three dimensional structures of the binding site of the two
      proteins, ADA and A1 adenosine receptor, in spite of lacking any homologies in
      the amino acid sequences.

PMID- 11989802
TI  - Leukotriene modifiers: novel therapeutic opportunities in asthma.
AB  - Cysteinyl leukotrienes (Cys-LT) are powerful proinflammatory autacoids that cause
      long-lasting bronchoconstriction, plasma leakage, increased mucus production;
      their biological activity suggests a prominent role in the etiopathology of
      asthma and several Cys-LT receptor antagonists and synthetase inhibitors have
      been developed as new antiasthmatic drugs. Zafirlukast was discovered by a
      mechanism-based approach to drug discovery; early structure-activity relationship
      analyses of the prototype SRS-A antagonist FPL-55712, lead to the identification
      of an indole-containing lead compound that was more specific than FPL-55712.
      Modifications were made on the lipid-like tail, indole backbone and acidic head
      region of this lead compound, resulting in potent and selective leukotriene
      receptor antagonists such as ICI-198615 and 204219 (zafirlukast). On the basis of
      successful results in preclinical asthma models, zafirlukast was recommended for
      clinical development and became the first leukotriene-modifier to be approved for
      the treatment of asthma. Leukotriene biosynthesis inhibitors (LSI) also represent
      a promising approach to the treatment of asthma and may theoretically provide a
      broader protection than Cys-LT receptor antagonists by inhibition of the
      synthesis of the two major leukotrienes, the Cys-LT and the chemotactic LTB4. The
      LSI BAY X-1005 is the result of a broad chemistry program that identified 15-HETE
      as an endogenous inhibitor of leukotriene synthesis and REV 5901 as a lead
      prototypic quinoline-based 5-lipoxygenase (5-LO) inhibitor. Clinical studies
      demonstrated the effectiveness of BAY X-1005 in experimental conditions such as
      allergen provocation and cold-air induced asthma. However, no consistent
      treatment effect in the overall asthma population (mild to moderately severe
      asthmatics) lead to discontinuation of its development.

PMID- 11989803
TI  - Identification and mapping of small-molecule binding sites in proteins:
      computational tools for structure-based drug design.
AB  - The number of protein structures is currently increasing at an impressive rate.
      The growing wealth of data calls for methods to efficiently exploit structural
      information for medicinal and pharmaceutical purposes. Given the three
      dimensional (3D) structure of a validated protein target, the identification of
      functionally relevant binding sites and the analysis ('mapping') of these sites
      with respect to molecular recognition properties are important initial tasks in
      structure-based drug design. To address these tasks, a variety of computational
      tools have been developed. Approaches to identify binding pockets include
      geometric analyses of protein surfaces, comparisons of protein structures,
      similarity searches in databases of protein cavities, and docking scans to reveal
      areas of high ligand complementarity. In the context of binding-site analysis,
      powerful data mining tools help to retrieve experimental information about
      related protein-ligand complexes. To identify interaction hot spots, various
      potential functions and knowledge-based approaches are available for mapping
      binding regions. The results may subsequently be used to guide virtual screenings
      for new ligands via pharmacophore searches or docking simulations.

PMID- 11989804
TI  - Synthesis and antiviral activity evaluation of some new 6-substituted 3-(1
      adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles.
AB  - A number of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole
      derivatives, containing the adamantyl moiety, were synthesized and examined in
      various viral test systems. No antiviral effects were noted with any of the
      compounds at subtoxic concentrations in cell culture.

PMID- 11989805
TI  - New benzimidazole derivatives as antimycobacterial agents.
AB  - A set of 2-alkylsulfanyl derivatives of 5-methylbenzimidazole was synthesized and
      evaluated for antimycobacterial activity. The structures of the compounds were
      confirmed by 1H NMR and IR data, and their purity by elemental analysis.
      Antimycobacterial activities against Mycobacterium tuberculosis and
      nontuberculous mycobacteria were expressed as the minimum inhibitory
      concentration. The substances exhibited significant antimycobacterial activity,
      in particular against both strains of Mycobacterium kansasii. The effect of the
      most active compound in the set, 3,5-dinitro derivative 3t, exceeded that of the
      standard isoniazide against M. kansasii and Mycobacterium avium.

PMID- 11989806
TI  - Simple spectrophotometric determination of cinnarizine in its dosage forms.
AB  - A direct, extraction-free spectrophotometric method has been developed for the
      determination of cinnarizine in pharmaceutical preparations. The method is based
      on ion-pair formation between the drug and three acidic (sulphonphthalein) dyes;
      namely bromocresol green (BCG), bromocresol purple (BCP) and bromophenol blue
      (BPB) which induces an instantaneous bathochromic shift of the maximum in the
      drug spectrum. Conformity to Beer's law enabled the assay of dosage forms of the
      drug. Compared with a reference method, the results obtained were of equal
      accuracy and precision. A more detailed investigation of the cinnarizine-BCG ion
      pair complex was made with respect to its composition, association constant and
      free energy change. In addition, this method was also found to be specific for
      the analysis of cinnarizine in the presence of some of the co-formulated drugs,
      such as pyridoxine hydrochloride and digoxin.

PMID- 11989807
TI  - Synthesis of new C-6 alkyliden penicillin derivatives as beta-lactamase
      inhibitors.
AB  - New penicillin, penicillin sulfone and sulfoxide derivatives bearing a C-6
      alkyliden substituent were prepared. Their chemical synthesis, in vitro
      antibacterial activity and inhibition properties against two selected enzymes
      representing Class A and C beta-lactamases are reported. Compounds 3a-c, 7a-c
      were able to inhibit either TEM-1 (a Class A enzyme, from Escherichia coli) or P
      99 (a Class C enzyme, from E. cloacae), or both enzymes, when tested in
      competition experiments using nitrocefin as the reporter substrate. However, when
      tested in combination with amoxicillin, the same compounds did not show
      synergistic effects against E. coli and E. cloacae strains producing TEM-1 and
      P99 enzymes, respectively. This finding is most likely related to poor
      penetration through the bacterial cell wall, as shown by using a more permeable
      isogenic E. coli strain. Interestingly, a synergistic effect against a strain of
      S. aureus which produces PC1-enzyme (a Class A beta-lactamase) was observed for
      compound 3a when used in combination with amoxicillin.

PMID- 11989808
TI  - Interaction of 1,2,4-substituted piperazines, new serotonin receptor ligands,
      with 5-HT1A and 5-HT2A receptors.
AB  - In the present paper, we describe affinities to 5-HT1A and 5-HT2A receptors of
      several new 1,2,4-trisubstituted piperazine derivatives. The affinities were
      compared with those described earlier for 1,4-disubstituted piperazines and the
      influence of the third (methyl) substituent on the affinity to both receptors is
      discussed. The difference between two- and three-substituted derivatives was
      rationalised in terms of molecular modelling of the respective ligand-receptor
      complexes. Additionally, the functional activity of some 1,2,4-trisubstituted
      piperazines for 5-HT1A receptor was examined in behavioural and biochemical
      models. The obtained results have shown that some trisubstituted compounds
      exhibited a higher affinity to 5-HT2A receptors than their respective
      disubstituted analogues (with the affinity to 5-HT1A receptors remaining the same
      or somewhat improving). The molecular dynamics simulations suggested that the
      presence of the third substituent in the piperazine ring of those compounds may
      induce stabilising effect on the ligand-receptor complexes. The results of the in
      vivo studies have shown that some of the examined trisubstituted piperazines (10
      13, 16, 17) exhibited properties of postsynaptic 5-HT1A partial agonists.
      Moreover, compounds 13 and 16 exhibited features of 5-HT1A presynaptic agonists
      in in vitro test, and compound 16 also in in vivo tests.

PMID- 11989809
TI  - Synthesis and preliminary pharmacological evaluation of trans-2-amino-5(6)-chloro
      6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes as dopamine receptor ligands.
AB  - A series of trans-2-amino-5(6)-chloro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H
      indenes were synthesized and evaluated for their binding affinity toward D1-like
      and D2-like dopamine (DA) receptors. The affinity and selectivity of these
      compounds were measured in a test involving displacement of [3H]SCH 23390 or
      [3H]YM-09-151-2, respectively, from homogenates of porcine striatal membranes.
      All tested compounds were poorly effective at DA receptors (Ki nM > 1000). The
      results suggest that introduction of chlorine substituent in five or six position
      of previously synthesized trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H
      indenes decreases both D1-like and D2-like receptor affinity.

PMID- 11989810
TI  - Synthesis and antitumour activity of stereoisomers of 4-hydroperoxy derivatives
      of ifosfamide and its bromo analogue.
AB  - Racemic mixtures and laevorotatory enantiomers of cis- and trans-4
      hydroperoxyifosfamide and 4-hydroperoxybromofosfamide possess high antitumour
      activity both in vitro and in vivo. However, no major differences in biological
      activity were observed among these stereoisomers.

PMID- 11989811
TI  - Solid-supported reagents for multi-step organic synthesis: preparation and
      application.
AB  - Since the early days of combinatorial chemistry solid-phase organic synthesis has
      been the method of choice for the production of large libraries. Solution-phase
      synthesis is again gaining importance especially for the synthesis of parallel
      arrays of smaller, focussed libraries containing single compounds with high
      degrees of purity. In the field of solution-phase library generation, the use of
      solid-supported reagents, catalysts and scavengers is emerging as a leading
      strategy, combining the advantages of both solid-phase organic synthesis (e.g.
      allowing the employment of an excess of reagent without the need for additional
      purification steps) and solution-phase chemistry (e.g. the ease of monitoring the
      progress of the reactions by applying LC-MS, TLC or standard NMR techniques). An
      account of some of the most recent advances in this area of research will be
      presented.

PMID- 11989812
TI  - Synthesis and cytotoxicity evaluation of thiophene analogues of 1-methyl-2, 3
      bis(hydroxymethyl)benzo[g]indole bis[N-(2-propyl)carbamate].
AB  - The cytotoxicity of the bis[N-(2-propyl)carbamates] 2 and 3 which are linked to
      thieno[i,j-g]indole scaffolds through methylene bridges were studied as thiophene
      analogues of prototype 1. Compounds 2 and 3 were evaluated in vitro against 60
      human-tumor cell lines derived from nine cancer-cell types and demonstrated, for
      compound 3 not only strong growth-inhibitory activities against leukemia cancer
      cells, but also fairly good activities against the growth of certain renal and
      ovarian cancer cell lines. Compound 2, the thieno[2,3-g]indole bis-carbamate,
      possessed only significant (MG-MID log10 GI50 = -4.89) and selective cytoxicity
      against NCI-HOP92 (non-small cell lung), MALME 3M (melanoma) and IGROV 1
      (ovarian) cancer cell with log10 GI50 values of -5.66, -5.48 and -5.47,
      respectively.

PMID- 11989813
TI  - Inhibition of activated murine T-lymphocytes by synthetic glycoglycerolipid
      analogues.
AB  - Glycoglycerolipid analogues, characterized by a glycerol aglicone beta-linked in
      position 2 to a glucose or galactose residue, and by a lipophilic C6 acyl chain
      on the glycerol unit, significantly inhibit proliferation of activated T cells.
      The inhibitory activity displayed by such synthetic compounds is comparable to
      the immunosuppressive properties shown by the natural glycolipids simplexides, to
      which they are structurally related. Vice versa, when the acyl chain is located
      on the sugar unit, no immunomodulating activity is observed, suggesting a strict
      relationship between the activity and the location of the acyl chain.

PMID- 11989814
TI  - The administrative infrastructure of clinical research.

PMID- 11989815
TI  - Assessment of toxicity in cooperative oncology clinical trials: the long and
      short of it.
AB  - Cancer therapy is associated with inherent adverse effects and the need for
      complete, consistent and accurate reporting of toxicity is paramount in
      multicenter cooperative oncology clinical trials. Accurate toxicity information
      is essential to weigh the costs and benefits associated with new treatment
      regimens. A major issue faced by investigators and clinical trial coordinators
      today is the lack of clear directions regarding what method should be used in
      toxicity assessment in cooperative oncology clinical trials. Research personnel
      are faced with two options: (1) to be proactive and use a "directed" method of
      toxicity assessment or (2) to simply follow the data trail and report selected
      toxicity based only on routine documentation in the chart. The differences
      between these two approaches may be immense depending on one's perspective. The
      purpose of this article is to review how the current methods of toxicity
      assessment evolved and discuss issues and concerns in toxicity assessment in a
      challenging healthcare environment where clinical trials continue to increase in
      complexity and workload through the use of novel and multimodality therapies. The
      potential implications for toxicity data management practices, data quality,
      patient care management and resource utilization are discussed.

PMID- 11989816
TI  - Issues and opportunities in quality end-of-life care.

PMID- 11989817
TI  - Coding a physics week.

PMID- 11989818
TI  - The hydrophobic moment and its use in the classification of amphiphilic
      structures (review).
AB  - Amphiphilic alpha-helices play a major role in membrane dependent processes and
      are manifested in the primary structure of a protein by the periodic appearance
      of hydrophobic residues. Based on these periodic sequences, the hydrophobic
      moment was introduced, <microH>, which essentially treats the hydrophobicity of
      amino acid residues as a two-dimensional vector sum and provides a measure of
      amphiphilicity within regular repeat structures. To identify putative amphiphilic
      alpha-helix forming sequences, hydrophobic moment analysis assumes an amino acid
      residue periodicity of 100 and scans protein primary structures to find the 11
      residue window with maximal <microH>. Taken with the window's mean
      hydrophobicity, <H0>, hydrophobic moment plot analysis uses the coordinate pair,
      [<microH>, <H0>] to classify alpha-helices as either surface active, globular or
      transmembrane. More recently, this latter analysis has been extended to recognize
      candidate oblique orientated alpha-helices. Here, the hydrophobic moment is
      reviewed and data to query the logic of using a fixed window length and a fixed
      residue angular periodicity in hydrophobic moment analysis are provided. In
      addition, problems associated with the use of such analysis to predict alpha
      helix structure/function relationships are considered.

PMID- 11989819
TI  - The molecular basis of the structure and function of the 5-HT3 receptor: a model
      ligand-gated ion channel (review).
AB  - The ligand-gated ion channel superfamily of neurotransmitter receptors are
      proteins responsible for rapid transmission of nerve impulses at the synapse and
      have, therefore, been the subject of intensive research for many years. The cys
      loop family, of which the 5-HT3 receptor is a member, includes the nicotinic
      acetylcholine receptor, the GABAA receptor and the glycine receptor. A diverse
      range of endogenous and artificial ligands activate these receptors, but,
      nevertheless, the family shares many similarities of structure and function.
      Several important questions, however, still remain to be determined, including
      the mechanism of agonist recognition at the binding site, the nature of the
      connection between the agonist binding and channel domains, the structure of the
      transmembrane regions and the mechanism of ion permeation and selectivity. This
      article reviews recent advances in the characterization of the molecular
      properties of the 5-HT3 receptor and their role in its function, and assesses its
      suitability as a model system for the study of the above questions.

PMID- 11989820
TI  - Multiple levels of Notch signal regulation (review).
AB  - Notch is a vitally important signalling receptor controlling cell fate
      determination and pattern formation in numerous ways during development of both
      invertebrate and vertebrate species. An intriguing pathway for the Notch signal
      has emerged where, after ligand-dependent proteolysis, an intracellular fragment
      of the receptor itself translocates to the nucleus to regulate gene expression.
      The nuclear activity of the Notch intracellular domain is linked to complexes
      regulating chromatin organization through histone deacetylation and acetylation.
      To allow the Notch signal to be deployed in numerous contexts, many different
      mechanisms have evolved to regulate the level, duration and spatial distribution
      of Notch activity. Regulation occurs at multiple levels including patterns of
      ligand and receptor expression, Notch-ligand interactions, trafficking of the
      receptor and ligands, and covalent modifications including glycosylation,
      phosphorylation and ubiquitination. Several Notch regulatory proteins have
      conserved domains that link them to the ubiquitination pathway, and
      ubiquitination of the Notch intracellular domain has recently been linked to its
      degradation. Different proteolytically derived isoforms of Notch have also been
      identified that may be involved in alternative Notch-dependent signals or
      regulatory mechanisms, and differences between the four mammalian Notch
      homologues are beginning to be appreciated.

PMID- 11989821
TI  - Exploring the whereabouts of GLUT4 in skeletal muscle (review).
AB  - The glucose transporter GLUT4 is expressed in muscle, fat cells, brain and
      kidney. In contrast to other glucose transporters, GLUT4 in unstimulated cells is
      mostly intracellular. Stimuli such as insulin and muscle contractions then cause
      the translocation of GLUT4 to the cell surface. Questions related to GLUT4
      storage compartments, trafficking to the surface membrane, and nature of the
      intracellular pools, have kept many groups busy for the past 20 years. Yet, one
      of the main questions in the field remains the universality of GLUT4 features.
      Can one extrapolate work done on fat cells to muscle or brain? Or vice-versa? Can
      one use cultures to predict GLUT4 behaviour in fully differentiated tissues? This
      review summarizes the authors' knowledge of GLUT4 biology in skeletal muscle,
      which is the predominant tissue for glucose homeostasis. The results are compared
      to those obtained with the fat cell system, and an attempt is made to assess the
      universality principle.

PMID- 11989822
TI  - P-glycoprotein misfolds in Escherichia coli: evidence against alternating
      topology models of the transport cycle.
AB  - P-glycoprotein (P-gp) is a drug transporter which pumps toxic hydrophobic
      compounds out of cells, conferring mutidrug resistance. P-gp is predicted to
      consist of 12 transmembrane alpha-helices and there is a strong body of
      experimental support for this model. However, a number of studies, including
      those on P-gp expressed in E. coli, have reported topologies with fewer than 12
      transmembrane alpha-helices, leading to the hypothesis that the transmembrane
      topology of the protein changes during function. It is well established that P-gp
      undergoes conformational changes during its transport cycle and it has been
      recently shown that these changes are large in magnitude and could, potentially,
      reflect a changing transmembrane topology. One therefore, reassessed the
      transmembrane topology of P-gp expressed in E. coli and compared it directly with
      the topology of the protein expressed in mammalian cells. It was clear that the
      transmembrane topology of the protein was different in the different cell types
      and that the misfolding of P-gp in E. coli was due to the misrecognition of
      multiple P-gp sequences as topogenic signals. Thus, the alternative transmembrane
      topologies reported for P-gp in E. coli are artefacts of the heterologous
      expression system used, and models based on such data in which the transmembrane
      topology changes during drug transport are unlikely to be correct. Instead, the
      large conformational changes observed during the transport cycle are more likely
      due to changes in alpha-helix packing.

PMID- 11989823
TI  - In situ assessment of erythrocyte membrane properties during cold storage.
AB  - Membrane fluidity and overall protein secondary structure of human erythrocytes
      were studied in situ using Fourier transform infrared spectroscopy (FTIR).
      Erythrocyte membranes were found to have weakly cooperative phase transitions at
      14 degrees C and at 34 degrees C, which were tentatively assigned to the melting
      of the inner membrane leaflet and the sphingolipid rich outer leaflet,
      respectively. Cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD)
      resulted in a large increase in the cooperativity of these transitions, and led
      to the appearance of another phospholipid transition at 25 degrees C. Multiple,
      sharp membrane phase transitions were observed after 5 days cold storage (4
      degrees C ), which indicated phase separation of the membrane lipids. Using
      fluorescence microscopy, it was determined that the lipid probe 1,1'-dioctadecyl
      3,3,3',3-tetramethyl-indocarbocyanine perchlorate (dil-C18) remained
      homogeneously distributed in the erythrocyte membrane during cold storage,
      suggesting that lipid domains were below the resolution limit of the microscope.
      Using thin layer chromatography, changes in the membrane lipid composition were
      detected during cold storage. By contrast, assessment of the amide-II band with
      FTIR showed that the overall protein secondary structure of haemoglobin was
      stable during cold storage.

PMID- 11989824
TI  - Targeted disruption of the mouse gene encoding the V-ATPase accessory subunit
      Ac45.
AB  - Acidification of organelles of the eukaryotic vacuolar system is important for
      multiple intracellular processes including receptor-mediated endocytosis,
      proteolytic activity in lysosomes, and prohormone sorting and processing in
      secretory granules. Responsible for the generation of a proton gradient across a
      membrane is vacuolar H(+)-ATPase (V-ATPase). How the activity of this
      multisubunit enzyme is regulated remains to be established. Accessory subunits of
      the V-ATPase may be involved in the organelle-specific regulation, one candidate
      being the chromaffin granular V-ATPase-associated protein Ac45. To assess the
      function of Ac45, we disrupted its gene by gene targeting in male mouse embryonic
      stem cells. We have successfully generated Ac45 null mutant (-IY) embryonic stem
      cells and injected them into C57BL/6 recipient blastocysts. The blastocysts were
      replaced into pseudopregnant foster mothers, giving rise to 16 littermates. One
      of these appeared to be a low-chimeric female mouse that died 6 weeks after
      birth. No signs of late abortion were detected in the foster mothers. The results
      suggest that the injected Ac45 null mutant embryonic stem cells affect the normal
      development of the blastocyst and are in line with knockout studies on other V
      ATPase subunits that point to an essential role for the V-ATPase in early
      embryonic development.

PMID- 11989825
TI  - VEGF and tumour angiogenesis. Impact of surgery, wound healing, inflammation and
      blood transfusion.

PMID- 11989826
TI  - Long-term effects of pneumatic dilatation on symptoms and lower oesophageal
      sphincter pressure in achalasia.
AB  - BACKGROUND: Pneumatic dilatation is an effective treatment for achalasia.
      Although follow-up studies have shown that its clinical benefit persists for
      years, it is still unknown whether the decrease in lower oesophageal sphincter
      (LOS) pressure is maintained over time. Our aim is to assess the long-term
      effects of pneumatic dilatation on symptoms and LOS pressure in patients with
      idiopathic achalasia. METHODS: Eleven consecutive patients with achalasia (7 men)
      underwent I (n = 5) or 2 (n = 6) pneumatic dilatations (Rigiflex dilator) in
      order to achieve a stable (>1 year) clinical remission. Clinical scores (0-12,
      with scores of <3 indicating remission) and LOS pressure (sleeve manometry) were
      determined before treatment, after 3 and 12 months, and then every year for 6
      years. RESULTS: No operative complications occurred. The patients showed a marked
      clinical improvement (2.0 (2.0-2.0), median (IQ range), after 3 months versus 8.0
      (7.2-9.0) before treatment; P < 0.001), which was maintained throughout the
      follow-up period. Concurrently, there was a marked decrease in LOS pressure (5.0
      (4.0-7.0) mmHg after 3 months versus 25.0 (20.0-36.2) before treatment; P <
      0.001), which also remained stable over time. CONCLUSIONS: One or two pneumatic
      dilatations induce stable clinical remission and a decrease in LOS pressure that
      remains unchanged over time. Our data further support the use of dilatations as
      first-line treatment of achalasia.

PMID- 11989827
TI  - Randomized clinical trial of laparoscopic versus open fundoplication: evaluation
      of psychological well-being and changes in everyday life from a patient
      perspective.
AB  - BACKGROUND: The laparoscopic approach in antireflux surgery might have an impact
      on the patient's daily activities and well-being. METHODS: Sixty patients were
      randomized to laparoscopic or open 360 degrees fundoplication. Data were
      collected by questionnaires and interviews preoperatively, 1 month and 6 months
      after operation. RESULTS: Five patients in the laparoscopic group were converted
      to open surgery. Psychological general well-being increased after surgery and
      reached norm values in both study groups. No significant differences were found
      between the two types of surgery in the per protocol analysis, while the domain
      self-control was significantly better after open surgery in the intention-to
      treat analysis. There was improvement of diet and sleep in both study groups;
      after 6 months, disturbed sleep was significantly more uncommon after open
      surgery. Dysphagia and flatulence were new symptoms that were reported after
      surgery. Overall perception of the results of the operation did not differ
      between the groups. CONCLUSIONS: Psychological general well-being, diet and sleep
      improved after both laparoscopic and open surgery. There were only small
      differences between the groups, but in some respects the results were better
      after open surgery.

PMID- 11989828
TI  - Short-term administration of glucagon-like peptide-2. Effects on bone mineral
      density and markers of bone turnover in short-bowel patients with no colon.
AB  - BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a newly discovered
      intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment
      improved the intestinal absorptive capacity of short-bowel patients with no
      colon. Additionally, GLP-2 treatment was associated with changes in body
      composition that included a significant increase in total body bone mass. This
      article describes the effect of GLP-2 on spinal and hip bone mineral density
      (BMD) and biochemical markers of bone turnover in these patients. METHODS: In an
      open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years)
      with small-bowel resection and no colon received 400 microg s.c. of GLP-2 twice
      daily for 5 weeks. Four received home parenteral nutrition (mean length of
      residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The
      outcome measures were the mean percent change from baseline in spinal and hip BMD
      measured by dual-energy X-ray absorptiometry, changes in four biochemical markers
      of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of
      calcium. RESULTS: Mean +/- s(x) (SEM) percent changes in spinal and hip BMD were
      1.1+/-0.4% (P < 0.05) and 1.9+/-0.8% (P = 0.06), respectively. The intestinal
      calcium absorption increased by 2.7% (P = 0.87). Serum ionized calcium increased
      in 5/8 patients with a concomitant decrease in serum PTH values. Three of the
      four markers of bone turnover decreased. CONCLUSION: A 5-week GLP-2
      administration significantly increased spinal BMD in short-bowel patients with no
      colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but
      may be related to an increased mineralization of bone resulting from an improved
      intestinal calcium absorption.

PMID- 11989829
TI  - Current features of peptic ulcer disease in Finland: incidence of surgery,
      hospital admissions and mortality for the disease during the past twenty-five
      years.
AB  - BACKGROUND: Medical therapy of peptic ulcer disease (PUD) has improved
      dramatically during the past 20 years with the introduction of modern
      antisecretory drugs as well as eradication therapy of Helicobacter pylori. During
      the 1990s, there has been a 3-fold increase in the consumption of histamine-2
      receptor antagonists and proton-pump inhibitors, but also an 8-fold increase in
      the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) in Finland.
      METHODS: The incidence of surgery, hospital admissions and mortality for PUD was
      analysed between 1972 and 1999; the data were collected from the National
      Research and Development Centre for Welfare and Health and from the National
      Centre for Statistics. In the analysis, the codes of the Intemational Statistical
      Classification of Diseases 8-10 were used. RESULTS: In 1987, 11.9 elective
      operations (per 10(5) inhabitants) were performed (mean of 2 consecutive years),
      but only 1.3 in 1997, a reduction of 89%. In 1987, 5.2 emergency operations for
      ulcer perforation or bleeding were performed, whereas there were 7.5 in 1997, an
      increase of 44%. The annual hospital admission rate increased from 38.3
      admissions (per 10(5) inhabitants) in 1972 (mean +/- s (standard deviation) of 5
      consecutive years) to 68.7 in 1992. This 79% increase was mainly due to bleeding
      from gastric ulcer in elderly women. The overall annual mortality rate increased
      between 1972 and 1992 from 6.4 to 8.4 deaths (per 10(5) inhabitants), i.e. by
      31%. The mortality rate from ulcer perforation and haemorrhage increased from 4.2
      deaths in 1972 to 7.3 deaths in 1992, i.e. by 74%. CONCLUSIONS: The increasing
      incidence rates of emergency surgery, hospital admissions and mortality for PUD
      in the 1980s and 1990s have started to decrease in the most recent years in
      Finland. This epidemiologic change probably reflects both the demographic change
      and an increased consumption of NSAIDs, among the elderly people, in particular.
      The most recent epidemiologic change may reflect an increased consciousness about
      the harmful effects of conventional NSAIDs. Regardless of the constantly
      occurring emergency surgery, elective surgery for PUD is hardly ever required
      today.

PMID- 11989830
TI  - Helicobacter pylori infection inhibits antral mucosal nitric oxide production in
      humans.
AB  - BACKGROUND: Inducible NO synthase expression is upregulated in H. pylori-infected
      gastric mucosa, suggesting increased NO synthesis as part of a host defense
      reaction. This study investigates actual NO production in the human antrum in
      situ. METHODS: Gastroscopy with antral biopsy sampling and intragastric
      tonometric NO assessments were performed on H. pylori-positive and -negative
      volunteers. The antral mucosal specimens were analyzed with regard to inducible
      NO synthase (Western blotting) and the presence of the endogenous NO synthase
      inhibitor asymmetric dimethylarginine (ADMA) as well as L-arginine. RESULTS:
      Mucosal expression of inducible NO synthase was markedly increased in H. pylori
      infected subjects compared to noninfected ones. The ratio between the tissue
      contents of L-arginine and asymmetric dimethylarginine was considerably lower in
      the infected group. Antral output of NO was similar in the two groups during
      baseline conditions. Following intragastric L-arginine exposure. the antral NO
      production in controls was unaltered (from 442 ppb +/- 104 to 286 ppb +/- 94),
      whereas it increased (from 524 ppb +/- 162 to 1066 ppb +/- 274) in the infected
      individuals. CONCLUSIONS: The study confirms that NO synthase expression is
      increased in H. pylori-infected antral mucosa. However, NO synthesis is
      restricted owing to the presence of pathogen-induced competitive NO synthase
      inhibitors such as methylated arginines.

PMID- 11989831
TI  - Role of Helicobacter pylori CagA+ infection in determining oxidative DNA damage
      in gastric mucosa.
AB  - BACKGROUND: Although Helicobacter pylori is a risk factor for gastric cancer, the
      role of the bacterium in the development of this malignancy is not defined
      precisely. Reactive oxygen species (ROS) could play an important role in
      carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to
      assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      sensitive marker of oxidative DNA injury, in gastric mucosa, according to H.
      pylori status and cytotoxic associated gene product A (CagA); 2) to determine the
      relationship between ROS generation and amount of 8-OHdG. METHODS: Gastric biopsy
      specimens were obtained from 60 consecutive patients. ROS generation was measured
      by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an
      immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody.
      RESULTS: 40/60 patients (67%) were H. pylori-positive. ROS generation was
      significantly higher in patients positive for H. pylori infection as compared to
      negative. 8-OHdG detection was performed in 30 patients in which CagA presence
      was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H.
      pylori-positive patients (13 CagA+ and 1 CagA-) and in 2/10 (20%) H. pylori
      negative patients. A significant correlation was found between ROS production and
      8-OHdG content. CONCLUSION: H. pylori infection by a CagA+ strain is associated
      with the highest production of ROS to which a severe oxidative DNA damage
      corresponds. This sequence of events could support the hypothesis that the oxygen
      free radicals-mediated damage due to H. pylori cytotoxic strains could be a
      driving force that leads from chronic gastritis to gastric carcinoma.

PMID- 11989832
TI  - Capsaicin-sensitive nerve fibres induce epithelial cell proliferation,
      inflammatory cell immigration and transforming growth factor-alpha expression in
      the rat colonic mucosa in vivo.
AB  - BACKGROUND: Capsaicin-sensitive nerve fibres protect gastrointestinal mucosa in
      animal models of mucosal injury by modulation of mucosal blood flow and mucus
      secretion. The aim of our study was to evaluate the effects of capsaicin
      sensitive nerve fibres in rat colonic mucosa on epithelial cell proliferation and
      transforming growth factor-alpha (TGFalpha) expression, which is important in
      mucosal defence, protection and repair. METHODS: Male Wistar rats received either
      a capsaicin enema with or without giving antagonists to calcitonin-gene-related
      peptide (CGRP) or substance P (SP) i.v. immediately prior to the capsaicin
      enemas; a capsaicin enema after sensory desensitization as described previously;
      or a vehicle enema. In all experiments, animals received 50 mg/kg BrdU i.v. and
      were killed at 2, 4, 8, 12, 24 and 48 h after the various treatments. Colonic
      mucosal specimens were evaluated microscopically for mucosal damage, changes in
      the numbers of inflammatory cells and BrdU-immunoreactive epithelial cell nuclei.
      In the same specimens, TGFalpha-mRNA and -protein expression were evaluated by RT
      PCR and Western blot analysis using standardized procedures. RESULTS: A
      significant increase in the number of mucosal inflammatory cells and an increase
      in BrdU-immunoreactive nuclei were detected following mucosal exposure to
      capsaicin. A 2-fold increase of TGFalpha mRNA and a 10-fold increase of TGFalpha
      protein expression were obtained 2-12 h after capsaicin enemas. The effects on
      the invading number of inflammatory cells and on the increase in BrdU
      immunoreactive epithelial cell nuclei were significantly reduced by both CGRP and
      SP antagonists and were abolished in rats previously sensory-desensitized.
      CONCLUSION: Capsaicin-sensitive nerve fibres modulate epithelial cell
      proliferation and TGFalpha expression in colonic mucosa as well as a migration of
      inflammatory cells into the colonic mucosa. These effects are mediated by the
      neurotransmitters CGRP and SP.

PMID- 11989833
TI  - A re-examination of the relationship between abuse experience and functional
      bowel disorders.
AB  - BACKGROUND: Previous research suggests that sufferers of irritable bowel syndrome
      (IBS) report a greater prevalence of sexually and physically abusive experiences
      than patients with organic gastrointestinal disorders and non-patient
      populations. This has led to suppositions that previous abusive experiences might
      predispose to the development of functional gastrointestinal disorders. This
      study aimed to investigate the hypothesis that the prevalence of previous abuse
      experiences in patients with functional bowel disorders (FBD) is greater than it
      is in patients with a painful organic bowel disorder and healthy control
      subjects. METHODS: Fifty-three idiopathic constipation patients were compared
      with matched control groups of 50 IBS patients, 51 Crohn disease patients and 53
      non-patient control subjects. Measures of previous abuse experiences were taken
      using a self-report questionnaire and a semistructured interview. Other
      questionnaires of psychological distress were also administered. RESULTS: No
      significant differences were found between all four groups, both for measures of
      abuse and for psychological distress. However, patients who reported past abuse,
      irrespective of their FBD status. demonstrated significantly higher levels of
      current psychological distress. CONCLUSIONS: These results challenge the current
      assumption that past abuse experiences may be significant in the later
      presentation of functional bowel disorders, but suggest that previous abuse
      experience might be related to a general level of psychopathology.

PMID- 11989834
TI  - Efficacy and tolerability of prucalopride in patients with constipation due to
      spinal cord injury.
AB  - BACKGROUND: Chronic constipation (CC) often occurs after spinal cord injury
      (SCI). Prucalopride is a novel, highly selective, specific serotonin4 receptor
      agonist with enterokinetic properties. We evaluate the tolerability and pilot
      efficacy of prucalopride in the treatment of CC due to SCL. METHODS: Double
      blind, placebo-controlled, pilot, phase 11, dose-escalation study. After 4 weeks'
      run in, patients received prucalopride 1 mg (n = 8) or placebo (n = 4); 11 new
      patients were randomized to prucalopride 2 mg (n = 8) or placebo (n = 3) once
      daily for 4 weeks. Patients recorded bowel function (diary) and assessed
      constipation severity and treatment efficacy (visual analogue scale (VAS) 0-100
      mm). Colonic transit times were determined. RESULTS: Compared with run in. mean
      changes in constipation severity (VAS) increased with placebo, but decreased with
      prucalopride 1 and 2 mg. The VAS score for treatment efficacy showed a clear dose
      response (medians 4, 52 and 73 for placebo, 1 and 2 mg, respectively). Diary data
      showed an improvement in average weekly frequency of all bowel movements over 4
      weeks within the 2 mg group (median 0.6; 95% CI 0.2; 1.2). There was a
      significant reduction in median colonic transit time with 2 mg (n = 4; -38.5 h
      (95% CI -80; -5)). Four patients (2 mg) reported moderate/severe abdominal pain,
      and two of these discontinued treatment. There were no clinically relevant
      effects on any of the safety parameters. CONCLUSION: This pilot study indicates
      that prucalopride can play an important role in the management of patients with
      CC due to SCI.

PMID- 11989835
TI  - Post-gastrectomy osteopenia in the rat: bone structure is preserved by retaining
      10%-30% of the oxyntic gland area.
AB  - BACKGROUND: The acid-producing part of the rat stomach (fundus) is rich in
      endocrine cells, i.e. ECL cells and A-like cells. The ECL cells operate under
      gastrin control and manufacture histamine, the chromogranin-derived peptide
      pancreastatin and an unidentified peptide hormone. The A-like cells produce
      ghrelin, a newly discovered growth hormone-releasing hormone. Surgical removal of
      the entire glandular stomach (gastrectomy, Gx) or the acid-producing part
      (fundectomy, Fx) causes osteopenia, which is striking in the calvaria. We
      speculate that the osteopenia develops after surgical removal of the fundus,
      because the fundus hosts agents that preserve bone. This study examines how much
      of the fundus is needed to preserve normal skull bone. METHODS: Increasing
      portions of the fundus were resected surgically. The serum gastrin, ghrelin and
      pancreastatin concentrations were measured. The rats were killed after 10 weeks
      and the calvariae were subjected to transillumination analysis and quantitative
      histomorphometry. RESULTS: Fx elevated serum gastrin in proportion to the amount
      of fundus resected, i.e., the more fundus that was resected, the higher the serum
      gastrin concentration. Serum ghrelin and pancreastatin concentrations were
      reduced proportionally to the amount of fundus resected. In rats subjected to 90%
      or 100% Fx, the calvariae displayed the anticipated pattern of bone loss. No bone
      loss was seen when 70% or less of the fundus was resected. CONCLUSIONS: The
      results of the present study indicate that 10%-30% of the fundic mucosa is needed
      to preserve bone. The Gx/Fx-evoked osteopenia may be explained by hormonal
      deficiency caused by surgically eliminating or diminishing one of the endocrine
      cell populations in the fundic mucosa.

PMID- 11989836
TI  - Wheat grass juice in the treatment of active distal ulcerative colitis: a
      randomized double-blind placebo-controlled trial.
AB  - BACKGROUND: The use of wheat grass (Triticum aestivum) juice for treatment of
      various gastrointestinal and other conditions had been suggested by its
      proponents for more than 30 years, but was never clinically assessed in a
      controlled trial. A preliminary unpublished pilot study suggested efficacy of
      wheat grass juice in the treatment of ulcerative colitis (UC). METHODS: A
      randomized, double-blind, placebo-controlled study. One gastroenterology unit in
      a tertiary hospital and three study coordinating centers in three major cities in
      Israel. Twenty-three patients diagnosed clinically and sigmoidoscopically with
      active distal UC were randomly allocated to receive either 100 cc of wheat grass
      juice, or a matching placebo, daily for 1 month. Efficacy of treatment was
      assessed by a 4-fold disease activity index that included rectal bleeding and
      number of bowel movements as determined from patient diary records, a
      sigmoidoscopic evaluation, and global assessment by a physician. RESULTS: Twenty
      one patients completed the study, and full information was available on 19 of
      them. Treatment with wheat grass juice was associated with significant reductions
      in the overall disease activity index (P=0.031) and in the severity of rectal
      bleeding (P = 0.025). No serious side effects were found. Fresh extract of wheat
      grass demonstrated a prominent tracing in cyclic voltammetry methodology,
      presumably corresponding to four groups of compounds that exhibit anti-oxidative
      properties. CONCLUSION: Wheat grass juice appeared effective and safe as a single
      or adjuvant treatment of active distal UC.

PMID- 11989837
TI  - Health-related quality of life and psychological distress in a population-based
      sample of Swedish patients with inflammatory bowel disease.
AB  - BACKGROUND: The chronicity of inflammatory bowel disease (IBD) and effects of
      medical and surgical treatments probably affect the daily lives of patients and
      may thus impair their health-related quality of life and psychological well
      being. METHODS: Health-related quality of life and psychological distress were
      investigated in a population-based Swedish sample of patients with IBD. A total
      of 492 patients, 331 with ulcerative colitis (UC) and 161 with Crohn disease
      (CD), filled out the Short Form-36 (SF-36), the Inflammatory Bowel Disease
      Questionnaire (IBDQ) and the Hospital Anxiety and Depression (HAD) scale.
      RESULTS: Patients with UC reported higher (superior) levels in all dimensions of
      health-related and disease-specific quality of life than did patients with CD.
      CONCLUSIONS: Having an ileostomy does not seem to affect patients' quality of
      life, while having ileoanal anastomosis appears to reduce patients' quality of
      life in several of the dimensions assessed. CD patients reported more anxiety and
      depression than did patients with UC. The higher psychological distress in the CD
      group could be explained by more severe symptoms of the disease. Having ileoanal
      anastomosis may lead to more anxiety and depression, while having an ileostomy
      does not.

PMID- 11989838
TI  - Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients
      with ulcerative colitis.
AB  - BACKGROUND: In ulcerative colitis (UC) the activation (i.e. nuclear
      translocation) of nuclear factor kappa B (NF-kappaB) is an important step in the
      regulation of cytokines secreted by lamina propria macrophages. Clinical trials
      suggest anti-inflammatory effects of locally administered butyrate in UC. The
      potential effects of butyrate on NF-kappaB activation in lamina propria
      macrophages of UC patients were investigated. METHODS: Eleven patients with
      distal UC were treated for up to 8 weeks with butyrate at 100 mM (n = 6) or
      placebo (n = 5) enemas. At entry and after 4 and 8 weeks, clinical status was
      noted and intestinal inflammation was graded endoscopically and histologically.
      Double-staining with antibodies against NF-kappaB (p65) and CD68 was employed to
      detect NF-kappaB and macrophages, respectively. RESULTS: In untreated patients,
      nuclear translocation of NF-kappaB was detectable in virtually all macrophages.
      Butyrate treatment for 4 and 8 weeks resulted in a significant reduction in the
      number of macrophages being positive for nuclear translocated NF-kappaB. In
      addition, butyrate significantly reduced both the number of neutrophils in crypt
      and surface epithelia and of the lamina propria lymphocytes/plasma cells. These
      findings correlated with a significant decrease in the Disease Activity Index
      (DAI). CONCLUSIONS: The decrease in DAI and mucosal inflammation in butyrate
      treated patients is associated with a reduction of NF-kappaB translocation in
      lamina propria macrophages. Since the inflammatory process in UC is mainly
      sustained by macrophage-derived cytokines, the known anti-inflammatory effects of
      butyrate may in part be mediated by an inhibition of NF-kappaB activation in
      these macrophages.

PMID- 11989839
TI  - Effects of platelet activating factor, butyrate and interleukin-6 on
      cyclooxygenase-2 expression in human esophageal cancer cells.
AB  - BACKGROUND: Epidemiological studies have indicated that non-steroidal anti
      inflammatory drugs (NSAIDs) can reduce the risk of esophageal squamous cell
      carcinoma (ESCC) by taking cyclooxygenase (COX) as the target enzyme. The
      pathophysiological regulation of COX-2 may play a role in carcinogenesis and in
      disease progression of esophageal carcinoma. METHODS: 59 ESCC samples were used
      to assess COX-2 expression in the tumor cells and four ESCC cell lines to
      investigate the effects of phorbol myristate acetate (PMA), platelet activating
      factor (PAF), n-sodium butyrate (n-BT) and interleukin-6 (IL-6) on the expression
      of COX-2. Expression of COX-2 was determined by immunohistochemistry (IHC) and
      reverse transcription-polymerase chain reaction (RT-PCR). Production of PGE2 was
      measured by a competitive enzyme immunoassay (CEIA). RESULTS: COX-2 expression
      was detected in 54.2% (32/59) of the pathological sections by IHC. COX-2
      expression in ESCC cells was significantly increased following treatment with PAF
      and n-BT. Increased production of PGE2 was detected in the culture media, and the
      secreted PGE2 in the culture media was proportional to the increased COX-2
      expression. The addition of IL-6 could also enhance COX-2 expression in ESCC
      cells. While NSAIDs could inhibit enzymatic activity of COX-2, they did not
      inhibit COX-2 gene expression in ESCC cells. PKC inhibitor, however, could
      abrogate PMA-induced COX-2 gene expression, but it did not block IL-6-induced COX
      2 expression. CONCLUSIONS: Our data suggest that COX-2 expression in ESCC cells
      could be upregulated by PMA, PAF, n-BT and IL-6. Nonetheless, IL-6-induced COX-2
      expression could be independent of PKC activation.

PMID- 11989840
TI  - Laparoscopic cholecystectomy: bile duct and vascular injuries: management and
      outcome.
AB  - BACKGROUND: This is a retrospective study of 32 consecutive patients referred in
      the period 1992-2000 for management of serious bile duct injuries caused by
      elective laparoscopic cholecystectomy. METHODS: The patients were referred on
      median 29 days (0 days to 34 months). Only 7 patients were referred immediately
      after discovery of the injury. At the local hospital, 25 patients underwent
      various procedures in attempts at repair. Ten of the patients were treated for
      bile duct strictures after previous repairs in other hospitals. RESULTS: At
      referral, 23 patients (72%) had complete transection of the bile duct, while 9
      had bile leakage injuries. Additional complications were occlusion of the right
      hepatic artery in 8 patients (24%) and occlusion of the mesenteric superior
      artery in 1 patient. Infectious complications were prominent in 21 patients
      (70%), 6 of whom had septicaemia. Operative management with hepaticojejunostomy
      Roux-Y was employed in 22 patients. Various non-operative strategies were chosen,
      including endoscopically or transhepatic stenting of the bile duct and
      embolization of the right hepatic artery. There was no difference in hospital
      stay between operative and non-operative procedures which on median was 16 days (
      range 7-69 days). Three patients died: one had thrombosis of the superior
      mesenteric artery, while the other two died of complications to bile peritonitis.
      Median observation period is 5 years (5 months to 8 years). Two patients have
      cholangitis; both had injury to the right hepatic artery. The other patients all
      had normal ultrasonograms of the liver and normal/almost normal liver function
      tests. CONCLUSIONS: Bile duct injuries continue to occur, are serious and may
      result in death. Injury to the right hepatic artery is present in many cases.
      Patients are referred late to a competent center, resulting in serious infection
      in 70%.

PMID- 11989841
TI  - Hemodynamic effects of a combination of octreotide and terlipressin in patients
      with viral hepatitis related cirrhosis.
AB  - BACKGROUND: Terlipressin or octreotide given alone has been used as the first
      line pharmacological treatment for acute variceal bleeding. In portal
      hypertensive animals, pre-infusion of octreotide followed by the addition of
      terlipressin has an additive or complementary effect on splanchnic hemodynamics.
      The current study was aimed at evaluating such a combination treatment in
      patients with cirrhosis and portal hypertension. METHODS: Patients were randomly
      assigned to receive either a placebo (n = 11) or an intravenous infusion of
      octreotide 100 microg/h after an initial bolus of 100 microg (n = 13).
      Thereafter, each patient received an intravenous injection of terlipressin 2 mg.
      Hemodynamic values were measured basally, 30 min after octreotide or placebo, and
      60 min after terlipressin. RESULTS: Placebo administration did not affect any of
      the hemodynamic values. Terlipressin administration resulted in expected changes
      in hepatic venous pressure gradient, hepatic blood flow and systemic
      hemodynamics. In contrast, octreotide administration significantly decreased
      hepatic blood flow but did not affect other hemodynamic values. After
      terlipressin administration, significant hemodynamic changes were observed that
      were similar to the hemodynamic changes with terlipressin alone. The magnitude of
      changes in hepatic venous pressure gradient, cardiac index and systemic vascular
      resistance were no different between the two groups of patients. The heart rate
      was significantly lower in patients receiving octreotide plus terlipressin than
      those receiving terlipressin alone. CONCLUSION: The current study showed that a
      combination of octreotide and terlipressin did not exert an additive effect in
      reducing hepatic venous pressure gradient in patients with cirrhosis. In
      addition, the systemic hemodynamic changes were comparable between the two
      groups.

PMID- 11989842
TI  - D-glucaric acid in common duct bile and relation to choledocholithiasis.
AB  - BACKGROUND: The aim was to investigate a possible association between D-glucaric
      acid (DGA), biliary bilirubin glucuronidation and brown pigment stones in the
      common bile duct. METHODS: A high performance liquid chromatography method with a
      strong cation resin (HPX-87H) was developed for measuring biliary DGA. Bile was
      obtained during ERCP by deep cannulation of the common bile duct in 100 patients
      with suspected biliary disease. RESULTS: The concentration of DGA in common bile
      duct bile was 60 (1.1-633) micromol l(-1) (median, range). The values were lower
      than previously reported. There were no differences in DGA concentrations in
      patients with common bile duct stones compared to patients without common bile
      duct stones, irrespective of stone type, cholesterol or brown pigment stones.
      Bilirubin conjugates in common duct bile did not vary with DGA concentrations.
      CONCLUSION: DGA is probably insignificant in the pathogenesis of common bile duct
      stones.

PMID- 11989843
TI  - Diagnosis of a gastric mucosa-associated lymphoid tissue lymphoma by endoscopic
      ultrasonography-guided biopsies in a patient with a parotid gland localization.
AB  - We report the case of a 32-year-old man with a low-grade mucosa-associated
      lymphoid tissue (MALT) lymphoma of the parotid gland associated with Sjogren
      syndrome. He underwent an upper endoscopy as part of the screening of a gastric
      localization which showed a diffuse non-specific gastritis. However, endoscopic
      ultrasonography (EUS) evidenced a focal wall thickening of the vertical portion
      of the smaller curvature. EUS-guided biopsies of this area disclosed a MALT
      lymphoma, whereas biopsies under endoscopy concluded to mild chronic gastritis.
      The search for Helicobacter pylori infection remained negative. Four months after
      treatment with anti-CD20 antibodies, EUS showed a diminution of the abnormal
      thickening of the second layer. Regression was confirmed histologically on new
      EUS-guided biopsies. MALT lymphoma is usually considered a localized disease;
      however, dissemination is probably more frequent than initially believed. Our
      case reflects the importance of a systematic screening for a gastric localization
      in patients with MALT lymphoma of the salivary glands. In this situation,
      association to autoimmune disease such as Sjogren syndrome is more likely to
      explain the gastric location than infection with H. pylori. Endoscopic
      ultrasonography has a major impact for the staging of gastric MALT lymphoma, but
      may also help diagnose focal infiltration by the disease.

PMID- 11989844
TI  - A modified fuzzy C-means algorithm for bias field estimation and segmentation of
      MRI data.
AB  - In this paper, we present a novel algorithm for fuzzy segmentation of magnetic
      resonance imaging (MRI) data and estimation of intensity inhomogeneities using
      fuzzy logic. MRI intensity inhomogeneities can be attributed to imperfections in
      the radio-frequency coils or to problems associated with the acquisition
      sequences. The result is a slowly varying shading artifact over the image that
      can produce errors with conventional intensity-based classification. Our
      algorithm is formulated by modifying the objective function of the standard fuzzy
      c-means (FCM) algorithm to compensate for such inhomogeneities and to allow the
      labeling of a pixel (voxel) to be influenced by the labels in its immediate
      neighborhood. The neighborhood effect acts as a regularizer and biases the
      solution toward piecewise-homogeneous labelings. Such a regularization is useful
      in segmenting scans corrupted by salt and pepper noise. Experimental results on
      both synthetic images and MR data are given to demonstrate the effectiveness and
      efficiency of the proposed algorithm.

PMID- 11989845
TI  - Modeling the axial extension of a transmission line source within iterative
      reconstruction via multiple transmission sources.
AB  - Reconstruction algorithms for transmission tomography have generally assumed that
      the photons reaching a particular detector bin at a particular angle originate
      from a single point source. In this paper, we highlight several cases of extended
      transmission sources, in which it may be useful to approach the estimation of
      attenuation coefficients as a problem involving multiple transmission point
      sources. Examined in detail is the case of a fixed transmission line source with
      a fan-beam collimator. This geometry can result in attenuation images that have
      significant axial blur. Herein it is also shown, empirically, that extended
      transmission sources can result in biased estimates of the average attenuation,
      and an explanation is proposed. The finite axial resolution of the transmission
      line source configuration is modeled within iterative reconstruction using an
      expectation-maximization algorithm that was previously derived for estimating
      attenuation coefficients from single photon emission computed tomography (SPECT)
      emission data. The same algorithm is applicable to both problems because both can
      be thought of as involving multiple transmission sources. It is shown that
      modeling axial blur within reconstruction removes the bias in the average
      estimated attenuation and substantially improves the axial resolution of
      attenuation images.

PMID- 11989846
TI  - Correction for ambiguous solutions in factor analysis using a penalized least
      squares objective.
AB  - Factor analysis is a powerful tool used for the analysis of dynamic studies. One
      of the major drawbacks of factor analysis of dynamic structures (FADS) is that
      the solution is not mathematically unique when only nonnegativity constraints are
      used to determine factors and factor coefficients. In this paper, a method to
      correct for ambiguous FADS solutions has been developed. A nonambiguous solution
      (to within certain scaling factors) is obtained by constructing and minimizing a
      new objective function. The most common objective function consists of a least
      squares term that when minimized with nonnegativity constraints, forces agreement
      between the applied factor model and the measured data. In our method, this
      objective function is modified by adding a term that penalizes multiple
      components in the images of the factor coefficients. Due to nonuniqueness
      effects, these factor coefficients consist of more than one physiological
      component. The technique was tested on computer simulations, an experimental
      canine cardiac study using 99mTc-teboroxime, and a patient planar 99mTc-MAG3
      renal study. The results show that the technique works well in comparison to the
      truth in computer simulations and to region of interest (ROI) measurements in the
      experimental studies.

PMID- 11989847
TI  - A shape-space-based approach to tracking myocardial borders and quantifying
      regional left-ventricular function applied in echocardiography.
AB  - This paper presents a new semi-automatic method for quantifying regional heart
      function from two-dimensional echocardiography. In the approach, we first track
      the endocardial and epicardial boundaries using a new variant of the dynamic
      snake approach. The tracked borders are then decomposed into clinically
      meaningful regional parameters, using a novel interpretational shape-space
      motivated by the 16-segment model used in clinical practice for qualitative
      assessment of heart function. We show how a quantitative and automatic scoring
      scheme for the endocardial excursion and myocardial thickening can be derived
      from this. Results illustrating our approach on apical long-axis two-chamber-view
      data from a patient with a myocardial infarct in the apical anterior/inferior
      region of the heart are presented. In a case study (five patients, nine data
      sets) the performance of the tracking and interpretation techniques are compared
      with manual delineations of borders using a number of quantitative measures of
      regional comparison.

PMID- 11989848
TI  - Learning contextual relationships in mammograms using a hierarchical pyramid
      neural network.
AB  - This paper describes a pattern recognition architecture, which we term
      hierarchical pyramid/neural network (HPNN), that learns to exploit image
      structure at multiple resolutions for detecting clinically significant features
      in digital/digitized mammograms. The HPNN architecture consists of a hierarchy of
      neural networks, each network receiving feature inputs at a given scale as well
      as features constructed by networks lower in the hierarchy. Networks are trained
      using a novel error function for the supervised learning of image
      search/detection tasks when the position of the objects to be found is uncertain
      or ill defined. We have evaluated the HPNN's ability to eliminate false positive
      (FP) regions of interest generated by the University of Chicago's (UofC) Computer
      aided diagnosis (CAD) systems for microcalcification and mass detection. Results
      show that the HPNN architecture, trained using the uncertain object position
      (UOP) error function, reduces the FP rate of a mammographic CAD system by
      approximately 50% without significant loss in sensitivity. Investigation into the
      types of FPs that the HPNN eliminates suggests that the pattern recognizer is
      automatically learning and exploiting contextual information. Clinical utility is
      demonstrated through the evaluation of an integrated system in a clinical reader
      study. We conclude that the HPNN architecture learns contextual relationships
      between features at multiple scales and integrates these features for detecting
      microcalcifications and breast masses.

PMID- 11989849
TI  - An X-ray-based method for the determination of the contrast agent propagation in
      3-D vessel structures.
AB  - A method for the determination of the contrast-agent propagation in vessel trees
      is presented. A standard three-dimensional (3-D) rotational angiography procedure
      is performed to reconstruct the morphology of the contrast-filled vessel tree in
      a 3-D volume. An additional fluoroscopy projection series acquired with a fixed
      projection angle delivers the temporal information of the bolus propagating. The
      mapping of the propagation information from the two-dimensional projections to
      the 3-D image data set is the topic of this paper. A symbolic tree structure is
      built up that represents the vessel tree including bifurcations. Neighborhood
      relations between vessel pieces are given in three dimensions. This facilitates
      filtering procedures and plausibility controls of the resulting time dependent 3
      D data set. The presented method proved to be accurate with phantom data and
      gives novel insight in the feeding structure of arterio-venous malformations and
      aneurysms.

PMID- 11989850
TI  - Spiral-CT-based assessment of tracheal stenoses using 3-D-skeletonization.
AB  - PURPOSE: Demonstration of a technique for three-dimensional (3-D) assessment of
      tracheal-stenoses, regarding site, length and degree, based on spiral computed
      tomography (S-CT). PATIENTS AND METHODS: S-CT scanning and automated segmentation
      of the laryngo-tracheal tract (LTT) was followed by the extraction of the LTT
      medial axis using a skeletonization algorithm. Orthogonal to the medial axis the
      LTT 3-D cross-sectional profile was computed and presented as line charts, where
      degree and length was obtained. Values for both parameters were compared between
      36 patients and 18 normal controls separately. Accuracy and precision was derived
      from 17 phantom studies. RESULTS: Average degree and length of tracheal stenoses
      was found to be 60.5% and 4.32 cm in patients compared with minor caliber changes
      of 8.8% and 2.31 cm in normal controls (p << 0.0001). For the phantoms an
      excellent correlation between the true and computed 3-D cross-sectional profile
      was found (p << 0.005) and an accuracy for length and degree measurements of 2.14
      mm and 2.53% respectively could be determined. The corresponding figures for the
      precision were found to be 0.92 mm and 2.56%. CONCLUSION: LTT 3-D cross-sectional
      profiles permit objective, accurate and precise assessment of LTT caliber
      changes. Minor LTT caliber changes can be observed even in normals and, in case
      of an otherwise normal S-CT study, can be regarded as artifacts.

PMID- 11989851
TI  - Cardiac sarcoma showing bone formation and neurogenic markers: report of a case.
AB  - A 54 year-old Japanese female with cardiac insufficiency was found to have a left
      atrial mass and smaller masses on the mitral valve. Excisional surgery of the
      masses and mitral valve replacement were carried out. In spite of intensive post
      operative radiation therapy, the patient died of intra-atrial recurrence and
      brain metastases after 8 months. Tumour cells were spindled to oval, were
      positive for vimentin, S100 protein and neurone specific enolase. Laminin and
      fibronectin were also demonstrated. Bone formation and myxoid areas were present.
      An ultrastructurally identifiable stromal component, possibly responsible for
      laminin and fibronectin staining, was also present. The merits of the two main
      diagnostic possibilities - a mesenchymal/fibroblastic sarcoma showing bone and
      aberrant S100 protein, and a malignant peripheral nerve sheath tumour with bone -
      were discussed. In practical terms, the tumour was given the diagnosis of
      unclassifiable sarcoma of the left atrium. Atrial sarcomas showing neural markers
      and bone formation are exceedingly rare, and this report adds a further
      exceptionally uncommon case to the literature.

PMID- 11989852
TI  - Nemaline myopathy: description of an adult onset case.
AB  - Nemaline myopathy is a rare congenital muscle disease, with neonatal or adult
      onset. We report clinical and ultrastructural study of a 73-year-old woman whose
      symptoms manifested at age 40 years with proximal muscle weakness, nocturnal
      cramps, muscle pain and walking impairment. Muscle biopsy showed rods and other
      typical findings suggesting nemaline myopathy. This myopathy should be taken into
      account in the differential diagnosis of adult onset myopathies. Only
      ultrastructural examination allows an exact diagnosis.

PMID- 11989853
TI  - The development of the tongue and morphological and cytological changes in taste
      discs of Rana esculenta.
AB  - From the 38th developmental stage of the tadpole of Rana esculenta the process of
      tongue formation consists in the fast growth of the lining of the oral cavity
      floor anteriorly and faucially. This process is accompanied by the development of
      taste organs on the dorsal side of the tongue. At developmental stages 39-42
      taste disc anlages are covered by a layer of ordinary epithelial cells. At these
      stages, in some cells of a taste disc single synaptic-like vesicles with an
      electron-dense core appear. Apart from that, as early as at stage 42
      differentiation of the cells of a taste disc can be observed at the
      ultrastructural level. It is only at the 44th stage that all cell types
      characteristic for the mature TD can be distinguished in TEM (i.e., taste cells,
      basal cells and three kinds of associate cells: mucous, wing and sustentacular).
      Starting from that stage changes in the cell membrane can be observed indicating
      the presence of afferent synaptic junctions. The antibody used in the experiment
      was raised against neuron-specific enolase (NSE). At each of the developmental
      stages investigated (38, 42, 45) nerve fibres within the connective tissue
      beneath the epithelium of a taste disc anlage were immunopositive for NSE. From
      stage 42 onwards neural elements present in the basal part of the epithelium of a
      taste disc anlage were also NSE-positive. Basal cells did not show immuno
      reactivity for NSE at any of the developmental stages investigated.

PMID- 11989854
TI  - Amphicrine carcinoma of breast with giant granules: an immunohistochemical,
      histochemical and ultrastructural study.
AB  - A moderately differentiated grade 2 invasive ductal carcinoma was diagnosed in
      the right breast of an 81-year-old woman. The uniform nuclear profiles and
      moderately abundant granular cytoplasm suggested a neuroendocrine tumour and a
      Grimelius stain was positive. Neurone specific enolase, synaptophysin and
      somatostatin stained positively, and casein was interpreted as positive although
      with some background staining. By electron microscopy, tumour cells possessed
      desmosomes, tonofibrils, intercellular lumina, lamina and dense granules. Rounded
      dense granules 160-480 nm in diameter resembled neuroendocrine granules. They
      were found in both luminal and basal areas. Fewer and much larger ('giant')
      granules had a rounded profile and were up to 5 microm across. The smaller
      cytoplasmic granules were mostly Grimelius-positive while giant granules were
      negative. The smaller granules were also uranaffin-positive, but no uranaffin
      positive cytoplasmic giant granules were encountered. Both small and giant
      granules were observed in lumina, and here both were uranaffin-positive.
      Intraluminal giant granules had a substructure of small pale lipid-like lacunae,
      and some had irregular profiles. The exceptional size of these exocrine granules
      is emphasised, and the nature of both the small and giant granules discussed in
      this amphicrine carcinoma.

PMID- 11989855
TI  - Increased expression of NOS and ET-1 immunoreactivity in human colorectal
      metastatic liver tumours is associated with selective depression of constitutive
      NOS immunoreactivity in vessel endothelium.
AB  - The absence of perivascular nerves in tumour vessels suggests that endothelium
      derived vasoactive substances [nitric oxide (NO) and endothelin-1 (ET-1)] may be
      key factors in controlling tumour blood flow during tumour growth and metastasis.
      We have studied the ultrastructural distribution and immunoreactivity of
      different NO synthase (NOS) isoforms and ET-1 in human colorectal metastatic
      liver tumour tissues using pre-embedding peroxidase-anti-peroxidase and post
      embedding immunoelectron microscopic triple gold labelling techniques.
      Dramatically lower NOS 1 immunoreactivity was observed in tumour vascular
      endothelium (1-3% and 15-20% in tumour and normal groups, respectively). As
      compared to control groups there were significantly less NOS3 immunopositive EC
      in metastatic tumour vessels (45-50% and 1-3% in normal and tumour groups,
      respectively). A striking rise in NOS2 was observed in tumour vessel endothelium
      (< 1% in normal and 65-70% in tumour vessel endothelium). ET-1 immunoreactivity
      levels were also significantly higher in tumour vessel endothelium (85-90% in
      tumour, 15-20% in normal group). This increased expression of NOS2 and ET-1
      immunoreactivity was accompanied by the increased expression of three NOS
      isoforms and ET-1 immunoreactivity in liver parenchymal cells. These data suggest
      that metastatic tumour vessel endothelium is characterized by increased
      expression of NOS2 and ET-1 and by decreases in NOS1 and NOS3. These
      characteristics are associated with the overexpression of all three NOS isoforms
      and ET-1 immunoreactivity in non-vascular cells.

PMID- 11989856
TI  - The ultrastructure of the mature spermatozoon of the bivalve Gafrarium tumidum
      (Bivalvia, Heterodonta, Veneridae, Circinae).
AB  - Using transmission and scanning electron microscopy, we have described the mature
      spermatozoon of the bivalve Gafrarium tumidum (Heterodonta, Veneridae, Circinae)
      for the first time. The spermatozoon of G. tumidum is the ect-aquasperm type. The
      head contains a slightly curved nucleus. At its apex is a short cone-shaped
      acrosome. The structure of the acrosome is typical of heterodont bivalves and two
      major components of the acrosome vesicle material can be distinguished. The
      midpiece is an annular band of five mitochondria which surround the centriole
      complex. Sperm ultrastructure of G. tumidum provides additional information for
      the existing Veneridae phylogeny.

PMID- 11989857
TI  - A light and electron microscopic quantitative analysis of nerve-immune cell
      contacts in the gut-associated lymphoid tissue of the mouse colon.
AB  - Light microscopy (LM) histochemistry and transmission electron microscopy (EM)
      have been used to investigate the structural relationship between immunocompetent
      cells and enteric nerves in the gut-associated lymphoid tissue (GALT) of the
      mouse colon, i.e., a) the scattered immune cells in the lamina propria, b) the
      lymphoid follicles and c) the cryptopatches. Nerve-immune cell contacts have been
      quantified by LM, using the osmium-zinc iodide procedure for visualizing nerve
      fibers. Appositions of nerves to immune cells have been studied by EM when the
      distance between the immune cell plasma membrane and the neurilemma was 200 nm or
      less. In the diffuse GALT a), the LM incidence of nerve-lymph cell and nerve
      plasma cell contacts has been calculated to be one and half and, respectively,
      three times greater than would be expected by chance alone (P < 0.0001 in both
      cases). EM showed close apposition of axonal varicosities, mostly containing 60
      nm diameter dense-cored vesicles, to B lymphoblasts/immunoblasts or plasma cells.
      In isolated lymphoid follicles b), nerve-immune cell contacts were identified
      almost exclusively in the T-cell dependent parafollicular regions; the incidence
      of such contacts, calculated by LM, did not exceed expected theoretical values.
      By EM, apposition of nerve varicosities to small/middle-sized lymphocytes
      containing cytoplasmic lysosomal granules was seen sporadically. Examination of
      nerve-immune cell contacts in cryptopatches c), a recently identified extrathymic
      T-cell generating compartment, allowed recognition of a small proportion of nerve
      lymph cell structural interactions, both at LM and EM. This study provides
      systematic quantitative data on the microanatomical relationship between enteric
      nerves and immune cells in the various GALT compartments. Findings suggest that
      such nerve-immune cell contacts might represent the structural foundation for
      communication between enteric nerves and the GALT.

PMID- 11989858
TI  - Giant-cell tumor of bone arising from the falx cerebri. A case report.
AB  - The histological and ultrastructural features of a giant-cell tumor of bone
      arising in the falx cerebri of a 27 year-old man are described. The tumor was
      embedded in the medial aspect of the left frontal lobe and was not attached to
      any of the bones of the skull. At surgery, the tumor was lightly adherent to the
      falx and was easily extracted. Histologically, the tumor was composed of
      mononuclear spindle-shaped and ovoid stromal cells, multinuclear giant cells
      containing 20-30 nuclei, and foci of osteoid and bone production. Hemorrhagic and
      cystic areas were also present within the tumor. Ultrastructurally, the spindle
      shaped cells resembled fibroblasts and were surrounded by small bundles of
      collagen fibrils. The ovoid cells contained numerous mitochondria, abundant rough
      endoplasmic reticulum, vesicles, lysosomes, phagosomes and osseous material in
      the cytoplasm suggesting their monocyte-macrophage lineage. These cells were
      closely apposed and displayed evidence of fusion in the form of focal and linear
      subplasmalemmal densities to form multinucleated giant cells with similar
      organelles and multiple nuclei. It is suggested that the primary giant cell tumor
      of the one arose from the metaplastic ossification of the falx. To our knowledge,
      a giant-cell tumor of bone arising from the falx cerebri has not been previously
      described.

PMID- 11989859
TI  - Sequential pictorial presentation of neural interaction in the retina. 2. The
      depolarizing and hyperpolarizing bipolar cells at rod terminals.
AB  - Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell.
      The synaptic connections of cone processes to each bipolar cell and
      presynaptically to the two rod-bipolar cell synapses establishes conditions for
      lateral interaction at this level. Thus, the cones raise the threshold for
      bipolar cell depolarization which is the basis for spatial brightness contrast
      enhancement and consequently for high visual acuity (Sjostrand, 2001a). The cones
      facilitate ganglion cell depolarization by the bipolar cells and cone input
      prevents horizontal cell blocking of depolarization of the depolarizing bipolar
      cell, extending rod vision to low illumination. The combination of reduced cone
      input and transient hyperpolarization of the hyperpolarizing bipolar cell at
      onset of a light stimulus facilitates ganglion cell depolarization extensively at
      onset of the stimulus while no corresponding enhancement applies to the ganglion
      cell response at cessation of the stimulus, possibly establishing conditions for
      discrimination between on- vs. off-signals in the visual centre. Reduced cone
      input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a
      light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'.
      Presynaptic inhibition maintains transmitter concentration low in the synaptic
      gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing
      proportional and amplified postsynaptic responses at these synapses. Perfect
      timing of variations in facilitatory and inhibitory input to the ganglion cell
      confines the duration of ganglion cell depolarization at onset and at cessation
      of a light stimulus to that of a single synaptic transmission.

PMID- 11989860
TI  - Submicroscopic anatomy of photoreceptors in the female scale insect Eupulvinaria
      hydrangeae (Homopteres, Coccideae).
AB  - The submicroscopic anatomy of the eye in female Eupulvinaria is described. This
      scale insect has no compound eyes but simple pericerebral eyes composed of one
      pair of ocelli. The ocelli, located dorsolaterally to the brain, are of
      rhabdomeric type. They are situated in the subepidermal region underneath the
      basement membrane of the epidermis. Each ocellus consists of a cup made of a
      layer of numerous pigmented cells enclosing a few photoreceptive cells. The
      cuticular lens is facing the opening of the pigment-cup, while the optic nerve is
      emerging from the bottom of the cup. Pigmented cells show characteristic pigment
      granules. They are linked to each other by interdigitations or by desmosomes
      junctions. Both dendrites and cell body of the photoreceptor cell lie inside the
      eyecup, while the axon lies outside. The dendritic processes consist of large
      shaft-shaped rhabdomeres with microvilli extending perpendicular to the direction
      of the shaft. These microvilli are enveloped by digitiform cytoplasmic extensions
      of pigmented cells. These latter strands are free of pigment granules but contain
      microtubules orientated to the centre of the cup.

PMID- 11989861
TI  - Further studies on the interaction of Toxoplasma gondii with neutrophils and
      eosinophils.
AB  - Tachyzoites of Toxoplasma gondii are ingested by neutrophils and eosinophils
      through a process which can be significantly inhibited by previous incubation of
      the host cells with cytochalasin D. Although dividing zoites within the
      leukocytes could be observed, after 3 h of infection, killing of parasites within
      the parasitophorous vacuole was detected. Cytochemical studies showed that both
      in neutrophils and eosinophils there is a process of NADP(H) oxidase activation,
      which was higher in the latter.

PMID- 11989862
TI  - Microscopic versus macroscopic biomass models in activated sludge systems.
AB  - Today's models of activated sludge systems are based on average composition of
      biomass (macroscopic models). With the introduction of cell internal storage
      compounds (structured biomass) in ASM2 and ASM3 cell composition influences the
      kinetic behavior of activated sludge. Since the kinetics of most processes is not
      linear, adding up the behavior of individual cells (microscopic models) does not
      result in the same model prediction as obtained when predictions are made with
      average cell composition. Based on first simple computations with microscopic
      models which consider up to 100,000 individual bacteria, differences in model
      prediction are identified. It becomes clear that kinetic parameters for lumped,
      macroscopic models are system specific: whereas biomass from SBR systems yields
      kinetic parameters suited for application in microscopic models--biomass from
      continuous flow systems can only be used for the calibration of macroscopic
      models. Application of SBR models to continuous flow systems requires the use of
      microscopic models.

PMID- 11989863
TI  - Measurement of microorganisms with PHA production capability in activated sludge
      and its implication in activated sludge model no. 3.
AB  - In Activated Sludge Model No.3 (ASM3), it is hypothesized that all heterotrophic
      microorganisms (X(H)) can store substrate. However, in reality, both
      microorganisms with and without substrate storage capability (X(H/STO) and
      X(H/S), respectively) could exist. If the ratio of X(H/STO) in activated sludge
      is influenced by operational and environmental conditions, kSTO (storage rate
      constant of heterotrophic microorganisms which is defined in ASM3) may not be a
      universal parameter and can change from case to case. In this study,
      polyhydroxyalkanoate (PHA) is assumed as the principal storage product, and the
      ratio of microorganisms with PHA production capability (X(H/PHA)) in various
      activated sludges was estimated by the dual staining of Nile Blue A (NB) and
      DAPI. It was shown that the ratio of X(H/PHA) in sludge varied among different
      municipal and laboratory activated sludges.

PMID- 11989864
TI  - Oligonucleotide probe hybridization and modeling results suggest that populations
      consuming readily degradable substrate have high cellular RNA levels.
AB  - Analyses based on ribosomal RNA (rRNA)-targeted hybridization performed in our
      laboratory identified two types of bacterial populations: a population with a
      high RNA level per biomass and a population with a low level of RNA per biomass.
      To extend these descriptions, the diurnal dynamics of the RNA pool were monitored
      by rRNA-targeted oligonucleotide probe membrane hybridization. Under the typical
      diurnal variation in COD loading rate experienced by municipal wastewater
      treatment plants, the RNA level of the bacterial population with a high level of
      RNA per biomass varied with changes in the COD loading rate. Under the same
      conditions, the RNA level of the population with low RNA level per biomass
      remained constant. A structured biomass model was developed to describe these
      data. Substrate COD was divided into a readily biodegradable and a slowly
      biodegradable COD fraction. It was assumed that two specialized populations
      coexist in municipal activated sludge treatment systems. One population consumes
      readily degradable COD and the other consumes slowly degradable COD. According to
      model simulations, the population consuming readily degradable COD has a high
      level of RNA per biomass under variable substrate concentrations. Comparatively,
      the population consuming slowly degradable COD has a low level of RNA level per
      biomass. Furthermore, model simulations reproduced the two diurnal RNA profiles
      observed in a full-scale municipal activated sludge system. Therefore, we suggest
      that two populations can be distinguished in municipal activated sludge systems:
      a population consuming readily degradable substrate and a population consuming
      slowly degradable substrate.

PMID- 11989865
TI  - A practical protocol for dynamic modelling of activated sludge systems.
AB  - Use of dynamic simulation models has become standard practice in The Netherlands.
      Since the introduction around 5 years ago more then 100 full scale wastewater
      treatment plants have been modelled. Initially very different approaches have
      been used varying in calibration approach, amount of sampling and time
      investment. Based on the accumulated practical experiences the Dutch Foundation
      of Applied Water Research STOWA has stimulated the development of a protocol to
      aid in the set-up and calibration of models for full scale wastewater treatment
      plants. Herein the aim was to develop a protocol, which in practice was easy to
      use, minimising time and costs effort, but give a reliable and useable method. In
      this paper this protocol is briefly described.

PMID- 11989866
TI  - Modelling of activated sludge processes with structured biomass.
AB  - Bacterial communities when subjected to feast-famine conditions as occurring in
      many wastewater treatment systems store substrates as reserve polymers. Including
      storage polymers in a description of microbial growth processes makes important
      the choice of kinetic relations. Presently there is no sound description for the
      diversion of substrate towards biomass growth or substrate storage. Based on
      observations with pure cultures and mixed cultures growing under dynamic
      conditions a model is proposed to describe such behaviour. This description is
      based on the observation that bacteria in order to grow fast have to induce a
      high level of RNA and proteins in order to allow fast growth. We assume that this
      protein synthesising system is only induced in the presence of external
      substrates. Based on this assumption a model structure is proposed and evaluated.
      It seems that this model can predict the turnover of PHA in the cells correctly,
      and describes well the overall behaviour mixed culture SBR systems. However
      especially the growth rate in the famine phase seems to be overestimated. The
      model defined here is a contribution to a further development of mechanistically
      based models for activated sludge processes.

PMID- 11989867
TI  - Effect of solids retention time and wastewater characteristics on biological
      phosphorus removal.
AB  - The paper deals with the effect of wastewater, plant design and operation in
      relation to biological nitrogen and phosphorus removal and the possibilities to
      model the processes. Two Bio-P pilot plants were operated for 2.5 years in
      parallel receiving identical wastewater. The plants had SRT of 4 and 21 days, the
      latter had nitrification and denitrification. The plant with 4 days SRT had much
      more variable biomass characteristics, than the one with the high SRT. The
      internal storage compounds, PHA, were affected significantly by the concentration
      of fatty acids or other easily degradable organics in the wastewater, and less by
      the plant lay-out. The phosphorus removal is mainly dependent on availability in
      the wastewater of fatty acids but also by the suspended solids in the effluent,
      which is higher in the plant with nitrification-denitrification, probably due to
      a higher SVI or denitrification in the settler. The addition of glucose to the
      influent seems to have an effect on the performance of the plants similar to that
      of acetic acid. In spite of great load variations over time to the pilot plants
      and the different operational modes, the study of population dynamics showed less
      significant variations with time which has importance in relation to modelling.
      The overall conclusion of the comparison between the two plants is that the
      biological phosphorus removal efficiency under practical operating conditions is
      affected by the SRT in the plant and the wastewater composition. Thus great care
      should be taken when extrapolating results from one type of plant to another.
      Indirectly the experiments confirm that results from lab-experiments with
      artificial wastewater are difficult to extrapolate through modelling to real life
      wastewater and conditions. The 2.5 years time series can be valuable in
      verification of models for Nitrogen and Enhanced Biological Phosphorus Removal.

PMID- 11989868
TI  - Error diagnostics and data reconciliation for activated sludge modelling using
      mass balances.
AB  - Research on activated sludge models is mainly directed towards the reliability
      and estimation of model coefficients. Model calculations however, rely heavily on
      accurate determination of operational conditions. Accurate measurement of
      operational conditions and mass flows is difficult, caused by large (full-scale)
      process flows and the absence of reliable measurements. Therefore operational
      data should be verified on (gross) errors before being implemented in model
      studies. Calibrating a model on erroneous mass flows leads to laborious
      calibration procedures and moreover, unjustified adaptation of the model (kinetic
      and stoichiometric) parameters. Gross error detection is possible when there are
      more measurements than strictly required to solve a system of linear conservation
      relations (mass balances). A simple method for error detection is evaluating the
      mass balance residuals. For over determined systems data accuracy can be improved
      using balancing methods (i.e. minimising balance residuals). This is referred to
      as data reconciliation. A reconciled data set contains fewer errors and is
      exactly in line with the mass balances of the system. In this paper we describe a
      method for gross error detection and data reconciliation. It is shown how data
      reconciliation improves the accuracy of the data set and how the use of a
      balanced data set simplifies the model calibration procedure. This is
      demonstrated on the basis of a modelling study of a full-scale WWTP.

PMID- 11989869
TI  - Effect of different carbon sources on aerobic storage by activated sludge.
AB  - A study of substrate removal by real activated sludge with several synthetic
      substrates (acetate, ethanol, glutamic acid) and wastewater (raw and filtered)
      was carried out. Substrate, stored compounds (polyhydroxyalkanoates, PHA and
      internal carbohydrates), ammonia and oxygen uptake rate (OUR) were analytically
      determined. Polyhydroxybutyrate (PHB) was stored when the substrate was acetate
      or ethanol, while no appreciable formation of storage compound was detected using
      glutamic acid. A low amount of PHB was also formed in tests with raw and filtered
      wastewater which was probably mainly due to its acetate content. As far as the
      sum of storage and growth (indirectly estimated through ammonia consumption) did
      not match the overall solids formation, other unidentified mechanisms of
      substrate removal were likely to occur (biosorption, accumulation and/or storage
      of unidentified compounds). ASM3 and two derived models were used in the
      interpretation of experimental data with reference to synthetic substrates. With
      reference to synthetic substrates ASM3 can well describe the experimental data
      only assuming a stored product formation much higher than the analytically
      detected one, whereas the model that assumes a parallel growth and storage on the
      substrate can well describe the observed stored product profile only assuming a
      direct contribution of growth much higher than estimated from ammonia
      consumption. The model that assumes an accumulation/biosorption stage as first
      step of substrate removal can better describe the whole experimentally observed
      behaviour. However as well as in ASM3 this implies that some fraction of removed
      COD is still unidentified. With reference to real wastewater where the different
      phenomena were mixed up due to the presence of several substrates, the different
      models gave similar results.

PMID- 11989870
TI  - Model-based evaluation of a new upgrading concept for N-removal.
AB  - Mathematical modelling is considered a time and cost-saving tool for evaluation
      of new wastewater treatment concepts. Modelling can help to bridge the gap
      between lab and full-scale application. Bio-augmentation can be used to obtain
      nitrification in activated sludge systems with a limited aerobic sludge retention
      time. In the present study the potential for augmenting the endogenous nitrifying
      population is evaluated. Implementing a nitrification reactor in the sludge
      return line fed with sludge liquor with a high ammonia concentration leads to
      augmentation of the native nitrifying population. Since the behaviour of
      nitrifiers is relatively well known, a choice was made to evaluate this new
      concept mainly based on mathematical modelling. As an example an existing
      treatment plant (WWTP Walcheren, The Netherlands) that needed to be upgraded was
      used. A mathematical model, based on the TUDP model and implemented in AQUASIM
      was developed and used to evaluate the potential of this bioaugmentation in the
      return sludge line. A comparison was made between bio-augmentation and extending
      the existing aeration basins and anoxic tanks. The results of both modified
      systems were compared to give a quantitative basis for evaluation of benefits
      gained from such a system. If the plant is upgraded by conventional extension it
      needs an increase in volume of about 225%; using a bioaugmentation in the return
      sludge line the total volume of the tanks needs to be expanded by only 75%
      (including the side stream tanks). Based on the modelling results a decision was
      made to implement the bioaugmentation concept at full scale without further pilot
      scale testing, thereby strongly decreasing the scale-up period for this process.

PMID- 11989871
TI  - Experience and extensions to the ASM2 family of models.
AB  - The development of ASM2 has created a complex model for biological phosphorus
      removal. Most of the published work on calibrating this model has focused on the
      design of experiments to maximise information with which to calibrate the model,
      or the use of hourly data collected around and within an aeration tank. But many
      sewage works do not collect such data, nor have such instrumentation. The
      application of ASM2 with sparse data collected at a low frequency, and mostly
      only input-output, is considered in this paper, based on data collected at a
      Swedish sewage works. This paper shows that ASM2 can be calibrated with such
      measurements. This paper also looks at a modification to ASM2d to better handle
      heterotrophic usage of volatile fatty acids, and the use of this model to study
      the effects of large increases in in-sewer storage on sewage treatment works.
      Concern about the generation of large quantities of VFAs, and their effect on the
      sewage treatment processes, was unfounded.

PMID- 11989872
TI  - Improving the predictions of ASM2d through modelling in practice.
AB  - The paper presents the adjustments carried out on the structure and in some
      default values of the kinetic coefficients of the ASM2d model in order to get an
      improved prediction for the experimental results obtained in pilot scale plants
      studies with different activated sludge treatment processes for carbon, nitrogen
      and phosphorous removal. In order to predict the high effluent filtered COD
      experimentally observed in high rate processes for carbon removal, a new model
      structure has been proposed, incorporating into the carbon model a soluble
      fraction of the slowly biodegradable substrate. Studies with the step feed and
      the alternating processes showed simultaneous nitrification-denitrification in
      aerated reactors which was predicted with increased values in the oxygen
      saturation coefficients for heterotrophic and autotrophic biomass. Both processes
      also showed loss of the denitrification capacity under unfavourable conditions,
      such us rains and low anoxic fraction, which required a very large decrease in
      the value of the reduction factor for denitrification so as to improve the
      predictions for effluent nitrate experimental results. Regarding phosphorus
      removal, the ASM2d model showed a satisfactory predictive capacity. For improved
      predictions of phosphorus release in anaerobic conditions, high values of the
      rate constant for storage of X(PHA) and low values of the anaerobic hydrolysis
      reduction factor were used. For phosphorus uptake in aerobic and anoxic
      conditions satisfactory predictions were obtained using the default values.

PMID- 11989873
TI  - Experiences with computer simulation at two large wastewater treatment plants in
      northern Poland.
AB  - Mathematical modelling and computer simulation have became a useful tool in
      evaluating the operation of wastewater treatment plants (WWTPs) in terms of
      nutrient removal capability. In this study, steady-state simulation results for
      two large biological nutrient removal WWTPs are presented. The plants are located
      in two neighbouring cities Gdansk and Gdynia in northern Poland. Simulations were
      performed using a pre-compiled model and layouts (MUCT and Johannesburg
      processes) implemented in the GPS-X simulation package. The monthly average
      values of conventional parameters, such as COD, Total Suspended Solids, total N,
      N-NH4+, P-PO4- were used as input data. The measured effluent concentrations of
      COD, N-NH4+, N-NO3- and P-PO4- as well as reactor MLSS were compared with model
      predictions. During calibration, performed from the process engineering
      perspective, default values of only five model parameters were changed. The
      opportunities for further applications of such models in municipal WWTPs are
      discussed.

PMID- 11989874
TI  - Combined hydraulic and biological modelling and full-scale validation of SBR
      process.
AB  - The biological reactions during the settling and decant periods of Sequencing
      Batch Reactors (SBRs) are generally ignored as they are not easily measured or
      described by modelling approaches. However, important processes are taking place,
      and in particular when the influent is fed into the bottom of the reactor at the
      same time (one of the main features of the UniFed process), the inclusion of
      these stages is crucial for accurate process predictions. Due to the vertical
      stratification of both liquid and solid components, a one-dimensional hydraulic
      model is combined with a modified ASM 2d biological model to allow the prediction
      of settling velocity, sludge concentration, soluble components and biological
      processes during the non-mixed periods of the SBR. The model is calibrated on a
      full-scale UniFed SBR system with tracer breakthrough tests, depth profiles of
      particulate and soluble compounds and measurements of the key components during
      the mixed aerobic period. This model is then validated against results from an
      independent experimental period with considerably different operating parameters.
      In both cases, the model is able to accurately predict the stratification and
      most of the biological reactions occurring in the sludge blanket and the
      supernatant during the non-mixed periods. Together with a correct description of
      the mixed aerobic period, a good prediction of the overall SBR performance can be
      achieved.

PMID- 11989875
TI  - The use of mathematical models in teaching wastewater treatment engineering.
AB  - Mathematical modeling of wastewater treatment processes has become increasingly
      popular in recent years. To prepare students for their future careers,
      environmental engineering education should provide students with sufficient
      background and experiences to understand and apply mathematical models
      efficiently and responsibly. Approaches for introducing mathematical modeling
      into courses on wastewater treatment engineering are discussed depending on the
      learning objectives, level of the course and the time available.

PMID- 11989876
TI  - Processes and modeling of hydrolysis of particulate organic matter in aerobic
      wastewater treatment--a review.
AB  - Carbon cycling and the availability of organic carbon for nutrient removal
      processes are in most wastewater treatment systems restricted by the rate of
      hydrolysis of slowly biodegradable (particulate) organic matter. To date, the
      mechanisms of hydrolysis are not well understood for complex substrates and mixed
      populations. Most mathematical models use a simple one-step process to describe
      hydrolysis. In this article, mechanisms of hydrolysis and mathematical models to
      describe these processes in wastewater treatment processes are reviewed.
      Experimental techniques to determine mechanisms of hydrolysis and rate constants
      are discussed.

PMID- 11989877
TI  - Modelling the activated sludge flocculation process combining laser light
      diffraction particle sizing and population balance modelling (PBM).
AB  - A technique based on laser light diffraction is shown to be successful in
      collecting on-line experimental data. Time series of floc size distributions
      (FSD) under different shear rates (G) and calcium additions were collected. The
      steady state mass mean diameter decreased with increasing shear rate G and
      increased when calcium additions exceeded 8 mg/l. A so-called population balance
      model (PBM) was used to describe the experimental data. This kind of model
      describes both aggregation and breakage through birth and death terms. A
      discretised PBM was used since analytical solutions of the integro-partial
      differential equations are non-existing. Despite the complexity of the model,
      only 2 parameters need to be estimated; the aggregation rate and the breakage
      rate. The model seems, however, to lack flexibility. Also, the description of the
      floc size distribution (FSD) in time is not accurate.

PMID- 11989878
TI  - Modelling wastewater transformation in sewers based on ASM3.
AB  - A deterministic model for wastewater transformations in the sewer that includes
      activity in the wastewater and in the sewer wall biofilm was developed. It is
      based on the Activated Sludge Model No. 3 (ASM3). The mass transfer processes in
      the biofilm were modelled with the effectiveness approach. This approach allowed
      for fast calculation, required only a limited number of parameters and gave good
      results. The ASM3 related parameters were calibrated and validated with
      laboratory experiments. An equation for the aeration of the wastewater through
      the water surface was determined with a method based on the inert gas sulphur
      hexafluoride. The other model parameters such as wall roughness, attachment of
      particles to the biofilm and biofilm erosion were calibrated and validated with
      field experiments in a main sewer. The resulting model described the oxygen
      concentration and wastewater respiration well. It can be easily linked for
      integrated urban hydrology modelling with the WWTP Activated Sludge Model and the
      newly proposed River Water Quality Model No. 1.

PMID- 11989879
TI  - The EAWAG Bio-P module for activated sludge model No. 3.
AB  - An additional module for the prediction of enhanced biological phosphorus removal
      is presented on the basis of a calibrated version of ASM3. The module uses
      modified processes from ASM2d but neglects the fermentation of readily degradable
      substrate. Biomass decay is modeled in the form of endogenous respiration as in
      ASM3. The glycogen pool and biologically induced P-precipitation is not taken
      into account. The module was systematically calibrated with experimental data
      from various batch experiments, a full-scale WWTP and a pilot plant treating
      Swiss municipal wastewater. A standard parameter set allowed all data to be
      simulated.

PMID- 11989880
TI  - Experience with guidelines for wastewater characterisation in The Netherlands.
AB  - In this paper experiences and results are presented with guidelines for
      wastewater characterisation that are standardised in The Netherlands for
      modelling purposes with ASM. The wastewater characterisation is based on a
      physical-chemical method to characterise the soluble and particulate fractions,
      combined with a BOD-analysis for characterising the biodegradable fraction of the
      influent COD. By following the guidelines, a sufficiently detailed and practical
      characterisation is obtained, and the results can be used for simulation studies
      on treatment plants for process optimisation, trouble-shooting and design
      assistance. At present, five years of experience is gained with the guidelines
      and they were used for the simulation of circa 100 treatment plants. The
      guidelines are evaluated as simple and easy to implement in routine analysis
      programs.

PMID- 11989881
TI  - Wastewater COD characterization: biodegradability of physico-chemical fractions.
AB  - Physico-chemical and biological characterization methods were applied to
      wastewater samples originating from 7 French WWTPs. The settleable fraction (S),
      unsettleable-coagulable fraction (US-C) and unsettleable-uncoagulable fraction
      (US-UC) were separated. Special emphasis was put on the determination of
      hydrolysis kinetics associated with coagulable- and settleable-fractions in order
      to model their behaviour in activated sludge processes, as both these fractions
      are influenced by the SRT. The "soluble" fraction (i.e. US-UC) was composed of
      readily biodegradable COD (2 to 27%), readily hydrolysable COD (37 to 90%) and
      inerts (2 to 47%). The "colloidal" fraction (i.e. US-C) was composed of
      heterotrophic biomass (9 to 24%) and readily hydrolysable COD (6 to 82%), with
      the rest being inerts or very slowly biodegradable COD (0 to 70%). The
      "particulate" fraction (i.e. settleable) was composed of biomass (14 +/- 6%),
      readily hydrolysable COD (21 +/- 14%), slowly hydrolysable COD (about 45-50%) and
      15 to 20% which can be considered as inert matter (X(I)). "Readily hydrolysable
      COD" was correctly modeled by a global first-order reaction. First-order
      constants (KH) were 9 +/- 2 d(-1) for raw-wastewater, 12 +/- 3 d(-1) for primary
      settled-wastewater and 16 +/- 5 d(-1) for coagulated-wastewater. "Slowly
      hydrolysable COD" was correctly modeled by a limited surface reaction. Concerning
      this fraction, the specific hydrolysis rate (kH) ranged from 0.25 to 1.05 d(-1),
      and the affinity constant (K(X)) ranged from 0.33 to 0.95 gCOD/gCOD based on
      settleable solids analysis.

PMID- 11989882
TI  - Use of phosphorus release batch tests for modelling an EBPR pilot plant.
AB  - The aim of this study was to evaluate how routinely performed phosphorus release
      tests could be used when modelling enhanced biological phosphorus removal (EBPR)
      using activated sludge models such as ASM2d. A pilot plant with an extensive
      analysis programme was used as basis for the simulations. Without any calibration
      the prediction of phosphorus removal was poor and the initial release rates from
      the simulations were not similar to those found from the laboratory tests. A
      period with low organic loading was chosen as a calibration period. In this
      period averages of daily influent measurements were used as influent parameters.
      First, calibration was performed in order to fit effluent COD and MLVSS in the
      sludge. Next, the phosphorus content in the sludge was decreased to the measured
      level by decreasing the fermentation rate. Finally, the initial phosphorus
      release rate was calculated from a simulated batch test and the PHA uptake rate
      was increased to fit this release rate with the average initial rates from
      laboratory batch tests performed during the period. The calibrated model was
      verified with data from the subsequent period where acetate was dosed.

PMID- 11989883
TI  - The planning and construction of an urban stormwater management scheme.
AB  - Water Sensitive Urban Design (WSUD) offers a means to integrate stormwater best
      management practices into urban planning and design to achieve multiple
      objectives. Some of these objectives relate to stormwater drainage, water quality
      improvements, aquatic habitat protection, stormwater harvesting and use, and
      landscape amenity. The Lynbrook Estate, Australia, has incorporated bio
      filtration systems and wetlands into the design of major roads, local access
      streets and parklands that attenuate and treat roof runoff and road runoff from a
      32 ha, 270 allotment residential precinct. This paper outlines the process that
      enabled the concept of a stormwater drainage design to be translated into on
      ground works. Details of the construction activities, costs and market acceptance
      highlight the potential for the adoption of similar practices elsewhere.

PMID- 11989884
TI  - Evaluation of the accumulation of sediment and heavy metals in a storm-water
      detention pond.
AB  - Accumulation of sediments and water quality were investigated in a wet storm
      water detention pond in central Sweden. The drainage area surrounding the pond
      was covered by a section of highway and secondary roads. Sediment samples were
      collected from the pond and heavy-metal concentrations analysed subsequently in
      the laboratory. The depth of accumulated sediments was measured at several points
      around the pond. The investigation showed that during the 18 months that had
      passed since the pond was constructed, a 5-8 cm layer of sediments had
      accumulated near the inlet, and a 1.5 cm layer near the outlet of the pond. Storm
      water passing through the detention pond showed an average reduction rate of 26
      84% for total metal content, 67% for total N, 78% for total P and 92% for COD.

PMID- 11989885
TI  - Infiltration and inflow in combined sewer systems: long-term analysis.
AB  - A study was conducted on 34 German combined sewer systems including combined
      sewer overflow (CSO) tanks and treatment plant to show up actual hidden reserves
      and bottlenecks in stormwater treatment. The study gave also a general insight
      into the water pathways in urban hydrology. A special focus was given to
      undesired non-polluted water infiltrating into the sewer, labelled infiltration
      and inflow (I/I) or infiltration inflows, which is widely underestimated. It
      leads to a bad performance of the drainage system although the parasite waters
      are themselves non-polluted. In existing combined systems, pollution control can
      be considerably improved by reducing I/I. It is equivalent to the reduction of
      surface runoff e.g. by a separate drainage as frequently proposed alternative.
      Artificial infiltration of surface runoff may even increase infiltration inflows.

PMID- 11989886
TI  - Impact of zinc roofing on urban runoff pollutant loads: the case of Paris.
AB  - Previous research on the Marais catchment in Paris demonstrated the very high
      zinc and cadmium contamination of runoff from zinc roofing. Thus further
      investigations were aimed at evaluating the relative importance of this type of
      roofing in Paris and its potential contribution to zinc and cadmium loads in wet
      weather flows. According to these results, about 40% of the surface of roofs in
      Paris is covered with rolled zinc (1016 ha), and this proportion is not likely to
      vary significantly in the next years, due to architectural rules. The Zn and Cd
      concentrations measured in runoff from these roofs are in accordance with
      literature

PMID- 11989887
TI  - Fine sediment retention in storage chambers: an assessment of time-dependent
      effects.
AB  - The optimisation of the design of a storage chamber is generally based upon some
      measure of the chamber's sedimentation efficiency. In the UK, chambers that
      minimise the deposition of fine sediments are preferred. Previous laboratory and
      CFD-based studies to measure efficiency have focused on steady flow conditions.
      However, both the flow hydraulics within a storage chamber and the pollutant
      loading in the incoming sewage vary markedly during storm events. This paper
      outlines a CFD-based approach for determining "overall" chamber efficiency. The
      approach employs an unsteady volume-of-fluid multiphase model and stochastic
      particle tracking. Preliminary results from a simplified two-dimensional model
      are presented.

PMID- 11989888
TI  - Developments in a methodology for the design of engineered invert traps in
      combined sewer systems.
AB  - Sediments within sewers can have a significant effect on the operation of the
      sewer system and on the surrounding natural and urban environment. One possible
      method for the management of sewer sediments is the use of slotted invert traps.
      Although invert traps can be used to selectively trap only inorganic bedload
      material, little is known with regard to the design of these structures. This
      paper presents results from a laboratory investigation comparing the trapping
      performance of three slot size configurations of a laboratory-scale invert trap.
      The paper also presents comparative results from a two-dimensional computational
      model utilising stochastic particle tracking. This investigation shows that
      particle tracking consistently over-predicts sediment retention efficiencies
      observed within the laboratory model.

PMID- 11989889
TI  - Design rules and impact assessment for source control measures based on
      continuous long-term simulations.
AB  - In recent years, more emphasis has been put on source control measures in order
      to reduce the peak runoff from urban areas during wet weather conditions. This
      involves the construction of upstream storage and infiltration facilities and
      rainwater tanks for reuse in households and the revaluation of ditches. Because
      of the long emptying times of source control facilities, a long antecedent period
      of rainfall influences the design. In addition, these facilities most often have
      an outflow which is not linearly varying with the storage. Because of the high
      variability of the rainfall, the required storage volumes can therefore only be
      assessed well if continuous simulations with long rainfall series are performed.
      Based on long-term simulations design rules have been set-up for source control
      measures in Flanders.

PMID- 11989890
TI  - Problems of modern urban drainage in developing countries.
AB  - Socio-economic factors in developing countries make it more difficult to solve
      problems of urban drainage than in countries that are more advanced. Factors
      inhibiting the adoption of modern solutions include: (1) in matters of urban
      drainage, 19th-century sanitary philosophy still dominates; (2) both legal and
      clandestine land settlement limits the space that modern solutions require; (3)
      contamination of storm runoff by foul sewage, sediment and garbage prevents
      adoption of developed-country practices; (4) climatic and socio-economic factors
      favour the growth of epidemics where runoff is retained for flood-avoidance and
      to increase infiltration; (5) lack of a technological basis for adequate drainage
      management and design; (6) lack of the interaction between community and city
      administration that is needed to obtain modern solutions to urban drainage
      problems. Awareness of these difficulties is fundamental to the search for modern
      and viable solutions appropriate for developing countries.

PMID- 11989891
TI  - Sediment transport in grassed swales during simulated runoff events.
AB  - Particle trapping in nine different grassed swales was measured successfully with
      a standardised runoff event simulation procedure. The percentage of total
      suspended solids removed ranged from 79 to 98%. It was found that sedimentation
      processes, rather than grass filtration governed the overall particle trapping
      efficiency. The highest particle trapping efficiency was observed in the field
      swales with dense, fully developed turf. A high infiltration rate was beneficial
      for the particle trapping and an increased swale length made it possible for
      smaller particles to be captured. A densely vegetated, ten metre long swale,
      receiving a stormwater flow of 1.0 litres per second, may capture a majority of
      the waterborne particles with settling velocities larger than 0.1 metres per
      hour. A simple model of particle trapping efficiency in grassed swales was
      developed and tested. It was found that mean swale residence time could be used
      as a design parameter for particle removal in grassed swales. The suggested
      exponential relationship between mean swale residence time and particle settling
      velocity associated with a certain trapping efficiency is so far only valid for a
      limited range of swale designs and residence times.

PMID- 11989892
TI  - Oil bio-degradation in permeable pavements by microbial communities.
AB  - This paper reports on continuing research at Coventry University into the
      improvement of highway water quality following flow through a permeable pavement.
      Such pavements have been shown elsewhere to be efficient in-situ bio-reactors,
      capable of degrading large quantities of clean motor oil. Further laboratory
      research, reported here, demonstrates that a commercially obtained oil degrading,
      microbial mixture was not significantly better at degrading clean motor oil than
      the indigenous microbial biomass established within the pavement over a 4-year
      period, when provided with an adequate nutrient supply. Scanning electron
      microscopy has been used to monitor biofilm development, which has also
      identified that the pavement has developed a complex community structure with
      high bio-diversity.

PMID- 11989893
TI  - Experimental study and modelling of zinc and lead migration in sandy soils due to
      stormwater infiltration.
AB  - Heavy metals emitted by road traffic are contaminants of roadside soils and can
      potentially migrate through the soils down to groundwater during runoff water
      infiltration. Stormwater management requires a better understanding of the
      mechanisms involved in the transport and particularly chemical interactions
      between heavy metals and the solid matrix. Experiments with open dynamic systems
      and modelling with a mixing-cells-in-series model have been performed to identify
      the main reactions which govern the migration of zinc and lead in sandy soils.
      Binary and ternary exchange experiments have been performed and a numerical
      modelling was proposed to describe zinc and lead mobility in column experiments.

PMID- 11989894
TI  - Developing, evaluating and maintaining a standardized stormwater BMP
      effectiveness database.
AB  - The Urban Water Resources Research Council of the American Society of Civil
      Engineers, under a cooperative agreement with the US Environmental Protection
      Agency, released Version 1.0 of the National Stormwater Best Management Practices
      (BMP) Database to the stormwater management community in 1999. The product
      included a loaded database of 71 BMPs, as well as data entry software for
      standardized reporting of BMP test data. In conjunction with the database, the
      project team developed BMP performance evaluation protocols and applied them to
      the data contained in the initial database. Since the initial database release,
      42 new BMP data sets have been added to the database, which is now accessible via
      the Internet at www.bmpdatabase.org along with associated data evaluation reports
      and other project documentation. A national stormwater BMP data clearinghouse
      continues to screen and post new BMP data to the database, as well as respond to
      inquiries from the public. An overview of both of the database software and
      results of the data evaluation are provided in this paper.

PMID- 11989895
TI  - Using typical daily flow patterns and dry-weather scenarios for screening flow
      rate measurements in sewers.
AB  - Monitoring systems for measuring rainfall, as well as flow rates and pollutant
      quantities conveyed by sewers and/or discharged by stormwater overflow devices,
      have become a common feature in many municipal sewer services, in part spurred by
      recent regulatory requirements. However, the state of measurement conditions in
      sewer facilities does not always ensure reliable results. For this reason, it is
      essential that measured values be carefully screened prior to their use, since
      many sources of disruption capable of skewing data can be encountered. The
      present article describes a method for validating dry-weather data a posteriori.
      This method relies upon flow rate forecasts, a combination of standard daily
      wastewater flow profiles and an estimation of infiltration flows. Measurement
      results are then compared with this forecast and an appropriate series of
      statistical tests are run to detect all major data anomalies. A number of
      diagnostic rules are then applied in order to derive an initial interpretation of
      these anomalies and, in particular, to identify the influence of rainfall events.

PMID- 11989896
TI  - Numerical and experimental investigations of the pollutant distribution in
      sewers.
AB  - Controlling flow and pollutant discharges through sewer networks is required for
      a number of reasons. In order to accomplish such control, precise knowledge of
      the hydrodynamic conditions of each candidate measurement location proves
      critical. The Laboratoire Central dos Ponts et Chausses has thus become involved
      in an experimental program on velocity and suspended matter concentration fields.
      This paper first presents the measurement methods and experimental results
      obtained before providing and discussing some of the numerical results.

PMID- 11989897
TI  - PID and PLC units for the real-time control of sewer systems.
AB  - Moveable gates for the real-time control (RTC) of sewer systems storage
      capacities are usually operated by controllers which, on the basis of local water
      level or flow velocity measurements, calculate the regulation errors of the
      monitored variables, determining the necessary regulator movements to lead the
      flow conditions to the desired set point. In this paper the results of an
      investigation on the influence of proportional-integral-derivative (PID)
      controllers and programmable logic controllers (PLC) for the RTC of moveable
      sluice gates positioned into sewer systems are presented. The analysis of
      response time, damping and regulation errors provided information on the PID
      parameter calibration values and on the PLC control function performances. A
      comparison between the two kind of controllers has also been carried out.

PMID- 11989898
TI  - Comprehensive geriatric assessment in oncology: pro.

PMID- 11989899
TI  - Multidimensional evaluation in geriatric oncology: the reasons "contra".

PMID- 11989900
TI  - Medical treatment of colorectal cancer in elderly (>70 years): GISCAD experience
      and future perspectives. Italian Group for the Study of Digestive Tract Cancer.

PMID- 11989901
TI  - Indications and feasibility of adjuvant chemotherapy in elderly patients with
      colorectal cancer.

PMID- 11989902
TI  - Single agents or combination chemotherapy for advanced ovarian carcinoma in
      elderly patients: pro single agents.

PMID- 11989903
TI  - Polychemotherapy in ovarian cancer in patients over seventy years of age.

PMID- 11989904
TI  - Prostate carcinoma.

PMID- 11989905
TI  - The management of bladder cancer in the elderly.

PMID- 11989906
TI  - Phase II single-agent studies in elderly cancer patients.

PMID- 11989907
TI  - Is it possible to use anthracyclines in patients older than 70 years? Pro.

PMID- 11989908
TI  - Is it possible to use anthracyclines in patients older than 70 years? Contra.

PMID- 11989909
TI  - Surgical treatment of bronchogenic carcinoma in elderly patients.

PMID- 11989910
TI  - Chemotherapy of advanced NSCLC in the elderly.

PMID- 11989911
TI  - Elderly patients with small cell lung cancer.

PMID- 11989912
TI  - The patient point of view.

PMID- 11989913
TI  - ZD1839 (Iressa): preclinical studies and pharmacology.

PMID- 11989914
TI  - Non Hodgkin's lymphoma in the elderly.

PMID- 11989915
TI  - Treatment of non-Hodgkin's lymphoma in the elderly. The Italian studies.

PMID- 11989916
TI  - Rituximab in combination with CHOP improves survival in elderly patients with
      aggressive non-Hodgkin's lymphoma.

PMID- 11989917
TI  - Treatment of elderly Hodgkin's lymphoma patients. The experience of the Italian
      Lymphoma Intergroup.

PMID- 11989918
TI  - Development of geriatric oncology in Italy.

PMID- 11989919
TI  - Carboplatin in elderly patients.

PMID- 11989920
TI  - Herceptin in elderly patients.

PMID- 11989921
TI  - Weekly paclitaxel infusion in elderly patients with solid tumors.

PMID- 11989922
TI  - An interesting antitumor drug in the elderly patients over the age of 70: weekly
      docetaxel.

PMID- 11989923
TI  - The clinical impact of cancer in the old-aged person.

PMID- 11989924
TI  - Surgical decisions in elderly cancer patients.

PMID- 11989925
TI  - Breast cancer: single agents chemotherapy.

PMID- 11989926
TI  - Polychemotherapy in overseventy breast cancer patients.

PMID- 11989927
TI  - Advanced breast cancer in elderly patients: which drug after tamoxifen?

PMID- 11989928
TI  - Elderly head and neck (H-N) cancer patients: a monoinstitutional series.

PMID- 11989929
TI  - Temozolomide in glioblastoma multiforme of the elderly.

PMID- 11989930
TI  - Ageing and cancer: the epidemiological point of view.

PMID- 11989931
TI  - Is there an advantage for oral therapy in elderly? UFT.

PMID- 11989932
TI  - Idarubicin.

PMID- 11989933
TI  - Pharmacokinetics of Navelbine oral in elderly patients.

PMID- 11989934
TI  - Breast cancer in 70 years old or older patients: tumor characteristics and
      prognostic factors.

PMID- 11989935
TI  - Results of adjuvant treatments in breast cancer patients over 70 years old: the
      IBCSG experience. International Breast Cancer Study Group.

PMID- 11989936
TI  - Results of adjuvant treatment in breast cancer women aged more than 70: Italian
      cooperative group experience.

PMID- 11989937
TI  - Should adjuvant chemotherapy be used to treat breast cancer in elderly patients
      (> or = 70 years of age)? Pro.

PMID- 11989938
TI  - Comorbidity and geriatric assessment in the elderly patient over the age of 70.

PMID- 11989939
TI  - Should adjuvant chemotherapy be used in elderly women (> or = 70 years) with
      breast cancer? Contra.

PMID- 11989940
TI  - Limits to the radiation therapy due to age.

PMID- 11989941
TI  - The Nicholas Perruche controversy: a French problem with wider implications.

PMID- 11989942
TI  - Smoking cessation--time to move forward.

PMID- 11989943
TI  - MRSA in Ireland. No frontiers to preventing spread but opportunities for control.

PMID- 11989944
TI  - Am I hearing the patient's complaint?

PMID- 11989945
TI  - Ambulatory paediatrics: does it work?
AB  - To determine whether a paediatric ambulatory assessment service is an effective
      and acceptable replacement for an inpatient unit. Analysis of hospital paediatric
      medical admissions. Postal questionnaire survey of local general practitioners.
      Telephone survey of parents of children who had attended the ambulatory service.
      Rural General Hospital in Northern Ireland. General practitioners. Parents of
      children referred to assessment service. Number of paediatric medical hospital
      admissions from the local area before and after the introduction of an ambulatory
      assessment service. General practitioner satisfaction levels. Parental
      satisfaction levels. Since the introduction of the new service in April 1996
      there has been a marked progressive reduction in paediatric medical hospital
      admissions from the local area. By the third year of operation of the ambulatory
      service (1998/99), a 47% reduction in admissions was recorded, compared to the
      1995/96 baseline year. The response rate to the general practitioner
      questionnaire was 65% (37 of 57) of whom most (31, 84%) found the service
      beneficial. Of the 37 respondents, 31 had referred patients to the service. The
      majority of these general practitioners (30, 97%) reported that the service was
      easy to access, and the same proportion felt that requests for consultation were
      met promptly. Most felt that feedback was appropriate (29, 94%). A telephone
      survey of 50 parents showed that most were either very satisfied (38, 76%), or
      satisfied (11, 22%) with the service. Most parents (41, 82%) felt their child had
      benefited by not being admitted to hospital. Most (46, 92%) felt they had
      received adequate information regarding their child's illness. A paediatric
      ambulatory assessment unit can reduce the number of children admitted to hospital
      and meet the needs of children, their families and general practitioners.

PMID- 11989946
TI  - Perinatal outcome in unbooked women at the Rotunda Hospital.
AB  - To determine the incidence and outcome of unbooked pregnancies in women at the
      Rotunda Hospital Retrospective case control study. All unbooked deliveries in the
      Rotunda Hospital over a two year period were identified and matched with a
      control. Control patients were selected as the next delivery after each case and
      were regular antenatal attenders. Demographic and obstetric data was collected
      from each case and control and compared using the Chi-square test. There were 101
      unbooked women in the study, during this time there were 11522 deliveries giving
      an incidence of unbooked pregnancies of 0.88%. Unbooked women were found to be
      young, multiparous, unemployed and unmarried. They were more likely to deliver by
      spontaneous vaginal delivery to preterm, low birth weight infants and were at
      greater risk of a stillbirth and neonatal death. Unbooked pregnancies account for
      a small proportion of our antenatal population. However, perinatal outcome is
      significantly worse in unbooked patients compared to those who are regular
      antenatal attenders.

PMID- 11989947
TI  - New onset seizures in the elderly: aetiology and prognosis.
AB  - Late onset epilepsy is increasing in incidence. These patients often have
      significant underlying morbidity. This retrospective study in a tertiary referral
      centre identified 68 patients aged 65 years or older, with new onset seizures
      over a four-year period. 81% of patients (n = 55) were followed up at an average
      of 2.7 years post diagnosis. 38% of patients had evidence of cerebrovascular
      disease (CT visualised focal infarction, haemorrhage or small vessel ischaemia in
      32%, clinical diagnosis with normal CT brain in 6%). No patient was found to have
      a space-occupying lesion. Of the 55 patients followed up, 45% of these had died
      at a mean age of 82 years old and 1.9 years post diagnosis (range 12 hours to 5
      years). Three patients died as a direct result of seizures (trauma and sepsis).
      14 patients died of clearly unrelated causes. Eight patients died from underlying
      vascular disease or Alzheimer's dementia. Patients who died during follow-up were
      on average 3.4 years older at the time of diagnosis than survivors (p< 0.05).
      Patients with atrial fibrillation at the time of diagnosis, had increased
      mortality (relative risk 2.53; 95% C.I. 1.19 - 5.36), but they were older than
      those without atrial fibrillation. At the time of follow up, 92% of those taking
      anti-convulsants were maintained seizure free on anticonvulsant monotherapy.

PMID- 11989948
TI  - Nail-gun limb injuries.
AB  - We present four cases and a review of the literature regarding nail-gun related
      limb injury. Nail guns have significant potential to cause limb and other major
      injuries. In most cases improper use of the nail-gun is the single most important
      factor in causing such types of injuries. Treatment of these injuries requires
      careful assessment of the limb and the type of nail involved in order to enable
      safe extraction. We recommend the introduction of training in the workforce to
      encourage awareness of the danger of such devices. We also emphasize the
      continuing requirements for improved workplace safety and adequate safety
      equipment when working with such dangerous devices.

PMID- 11989949
TI  - Pregnancy-associated breast cancer.
AB  - Twelve premenopausal women diagnosed with pregnancy-associated breast cancer
      between May 1985 and October 1999 were reviewed. Three patients were diagnosed in
      the first trimester of pregnancy, five in the second trimester, and three during
      the third trimester. There was one patient who was five weeks postpartum. At the
      time of diagnosis nine patients had lymph node involvement and two of these had
      metastatic disease. Four patients received primary chemotherapy. The remainder
      had surgery. Five patients died, two had metastatic disease at time of diagnosis,
      median survival was 31 months. There were three fetal deaths, one termination and
      two during primary chemotherapy. The diagnosis of breast cancer during pregnancy
      is difficult. Presentation is usually at an advanced stage. Surgery can be safely
      performed during pregnancy and adjuvant chemotherapy should not be postponed
      until after delivery.

PMID- 11989950
TI  - The establishment of a hospital clinical ethics committee.
AB  - In the Republic of Ireland the establishment of Clinical Ethics Committees (CECs)
      are relatively new. The need for such committees has occurred due to the fact
      that the consideration of ethical issues in healthcare has become an important
      and frequent part of discussions by individuals and institutions. A number of
      factors have contributed to this growth of ethical considerations. The Bon
      Secours Health System (BSHS) decided to establish a CEC and appointed a co
      ordinating team to draw up terms of reference for such a committee. During this
      process the co-ordinating team drew on the experience of other countries and of
      its own staff. Potential criticisms of how such a committee would function were
      examined. A representative membership of the CEC was also arrived at. The
      following functions were identified for a CEC: the need to provide a mechanism
      for the identification, discussion and resolution of medical ethical issues; the
      need to identify medical ethical issues which may create challenges to the health
      system and to monitor the responses of the health system to these areas, and the
      provision of education. Policy development was seen as a primary function of the
      CEC. Ethical case review also emerged as one area of potential involvement by the
      CEC. During the staff consultation a large number of ethical issues emerged which
      the staff requested the CEC to address. A methodology necessary for coping with
      the differences within the BSHS was developed by the CEC. It is evident that CECs
      are here to stay and how they develop and function will have an impact on the
      quality of healthcare.

PMID- 11989951
TI  - Hereditary cerebral cavernous angiomas: presentation as idiopathic familial
      epilepsy.
AB  - In cavernous angiomas of the brain, abnormally dilated blood vessels are tightly
      clustered together with no intervening neural parenchyma. Commonly recognised as
      a sporadic finding, these lesions may also be inherited in an autosomal dominant
      fashion. This disorder was recognised as a common entity with the advent of MRI.
      As lesions were often not detected on CT imaging, symptomatic patients presenting
      with seizures were mistakenly diagnosed with an idiopathic seizure disorder.
      Seizures are the commonest presenting symptom followed by haemorrhage and focal
      neurologic deficit. We present another cause of familial epilepsy that also
      emphasises the importance of MRI as the modality of choice in investigating
      seizures in children.

PMID- 11989952
TI  - Outcome of acute intussusception in a regional paediatric centre.
AB  - It has been suggested recently that acute intussusception should only be managed
      in a specialised paediatric centre. The aim of this study is to assess the
      incidence and outcome of acute intussusception in a comprehensive paediatric unit
      in Waterford Regional Hospital. It is a retrospective medical records study over
      a ten year period from June 1990 to June 2000. Our results showed that we had 24
      cases giving an incidence of 2.4 cases per year. Contrast enema was performed in
      23(95%) cases, successfully reduced in 14(61%) cases, unsuccessfully reduced in
      7(30%). Surgical intervention was necessary in 7(30%) cases. Three (12.5%) cases
      were transferred to a specialised paediatric surgical centre. There were no
      perforation or death. We conclude from this study that management of acute
      intussusception can be successfully undertaken in a regional paediatric centre.
      It requires adequate throughput of cases and close co-operation between
      paediatrician, radiologist, anaesthetist, surgeons and of course a dedicated
      paediatric nursing staff.

PMID- 11989953
TI  - Gatekeeping.

PMID- 11989954
TI  - Management of snoring.

PMID- 11989955
TI  - Managed care and the US health care system a social exchange perspective.
AB  - Many countries are importing managed care and price competition from the US to
      improve the performance of their health care systems. However, relatively little
      is known about how power is organized and exercised in the US health care system
      to control costs, improve quality and achieve other objectives. To close this
      knowledge gap, we applied social exchange theory to examine the power relations
      between purchasers, managed care organizations, providers and patients in the US
      health care system at three interrelated levels: (1) exchanges between purchasers
      and managed care organizations (MCOs); (2) exchanges between MCOs and physicians;
      and (3) exchanges between physicians and patients. The theory and evidence
      indicated that imbalanced exchange, or dependence, at all levels prompts behavior
      to move the exchange toward power balance. Collective action is a common strategy
      at all levels for reducing dependence and therefore, increasing power in exchange
      relations. The theoretical and research implications of exchange theory for the
      comparative study of health care systems are discussed.

PMID- 11989956
TI  - Regional differences in functional status among the aged.
AB  - This study investigated regional differences in functional status among aged
      Medicare beneficiaries in the United States, and the degree to which population
      risk factors and certain geographic/environmental attributes of communities
      accounted for the regional differences. Four years of the Medicare Current
      Beneficiary Survey (1992-1995) were pooled together yielding 37,150 person-year
      observations of functional status for a sample of aged Medicare beneficiaries
      residing in the community or nursing homes. Multinomial logit models, estimated
      on a four-category functional status scale, produced strong empirical evidence of
      substantial regional differences in the prevalence of functional independence,
      functional limitations, IADL limitations, and ADL limitations, that could not be
      attributed to regional population composition, socio-demographic factors,
      lifestyle characteristics, and chronic medical conditions. Although such
      population risk factors accounted for much of the regional variations in
      functional status among older men, the notably higher prevalence of IADL and ADL
      limitations among older women residing in the Deep South could not be similarly
      attributed to such risk factors. Rather, the empirical results suggest that a
      significant portion of the harmful effects associated with residence in the Deep
      South among older women may be attributed to a higher prevalence of residence in
      counties characterized by lower population density and/or higher poverty
      concentration.

PMID- 11989957
TI  - The construction of community participation: village family planning groups and
      the Indonesian state.
AB  - Indonesia's family planning program has been one of the most effective in the
      developing world in promoting contraceptive use and contributing to fertility
      transition. In evaluating why the program has worked, analysts have given much
      credit to a network of village family planning groups that developed from the
      1970s to the 1990s and that blanketed the archipelago. These groups, composed
      primarily of female volunteers, made contraception available to women in even the
      most remote parts of the country, and acted as agents of family planning
      motivation. They have been labeled by the Indonesian state family planning agency
      as an example of effective community participation on a national scale. In this
      paper, I investigate this claim and find it to be simplistic. I provide extensive
      evidence that the creation of this network was orchestrated by the Indonesian
      state. On the other hand, I show that these groups are not fully state entities,
      as they have several characteristics that mark them as socially embedded
      institutions. They are best labeled as unusual state-society hybrids. In my
      investigation I draw on one of the newest paradigms in the discipline of
      political science--the state-society approach--to uncover the odd nature of this
      family planning network. More deeply, I argue that the state-society approach
      ought to be adopted in family planning analysis on a comprehensive basis. The
      traditional organizational and social-demographic approaches that have dominated
      the field offer only limited understanding of the nature of family planning
      programs in developing countries. The state-society approach is ideally suited to
      identifying how family planning programs are institutions of a political nature,
      embedded in states and societies, and transformed by and transformative of each.

PMID- 11989958
TI  - Users' understanding of medical knowledge in general practice.
AB  - Much emphasis is now being placed on the quality of medical care, and various
      ways are being developed to assess the medical knowledge of general
      practitioners. It is increasingly recognised that the users perspective on health
      care is important, and that the views of health care professionals do not and
      cannot represent patients' views. In order to explore whether or not a large
      scale survey, which asked people to rate their doctors' medical knowledge,
      yielded meaningful results, this paper draws on findings from a study involving
      in-depth interviews with 26 lay people who had already completed the General
      Practice Assessment Survey questionnaire. When completing the questionnaires,
      patients had been asked to consider the 'technical care' provided by their
      general practitioners and to make a judgement about their doctors' medical
      knowledge. When interviewed at a later date, some people explained that they
      defined medical knowledge as knowledge of 'disease and treatments', while others
      defined it as knowledge of the 'whole person', and some defined a knowledgeable
      doctor as one who would acknowledge uncertainty. Patients appeared to have made
      judgements about their general practitioners' medical knowledge based on many
      factors, such as their experience of illness, perceptions of professional
      training, contact with other health care professionals in both primary and
      secondary care, and exposure to the media. The paper discusses the nature of
      medical knowledge, and concludes that although patient surveys are useful for the
      evaluation of interpersonal care and access to care, asking patients about their
      general practitioners' medical knowledge may yield invalid results. This is
      partly because patients defined medical knowledge in different ways, and partly
      because it appears that relatively few patients had enough knowledge about their
      own particular illnesses, or about possible alternative treatments, to make
      informed judgements about their general practitioners' medical knowledge.

PMID- 11989959
TI  - Construction of a GP integration model.
AB  - There are frequent calls to improve integration of health services, within and
      between primary and secondary care sectors. In Australia, general medical
      practitioners (GPs) are central to these endeavours. This paper aims to better
      conceptualise GP integration and to develop a model and index based on this. A
      conceptualisation of integration is proposed based on integration fundamentally
      as an activity or process not structure. Integration process is the frequency and
      quality of episodes of information exchange involving the GP and another
      practitioner or patient and aimed at fulfilling the objectives of the health care
      system with regard to patient care. These are both direct responses to structural
      forces and emergent GP capacities and dispositions. The content of this typology
      was studied using Concept Mapping in 11 groups of GPs, consumers and other
      practitioners. Clusters of related statements within thematic domains were used
      as the basis for a provisional model. This was tested using confirmatory factor
      analysis in a data set derived from a national probability sample of 501 GPs.
      Some re-specification of the model was necessary, with three integration process
      factors needing to be subdivided. One factor congeneric model assumptions were
      used to identify the constituent items for these factors. The result was a model
      in which 50 items measured nine integration process factors and 20 items measured
      five enabling factors. Two distinct but correlated higher order factors, relating
      to individual patient care and public (or community) health--in contrast to a
      single higher order factor for integration--were identified. The re-specified
      model was tested with a new sample of 151 GPs and exhibited strong psychometric
      properties. Reliability and validity were acceptable to this stage of the
      indices' development. Further testing of the index is necessary to demonstrate
      factor invariance of the indices in other contexts as well as their utility in
      cross-structural analysis. That said, the indices have immediate uses.

PMID- 11989960
TI  - "Women enjoy punishment": attitudes and experiences of gender-based violence
      among PHC nurses in rural South Africa.
AB  - Violence against women is pervasive in South Africa where, as in many other
      countries, cultural values and norms serve to condone and reinforce abusive
      practices against women. Primary health care nurses, who are widely distributed
      throughout the rural areas, may appear to be an ideal network for addressing this
      issue in resource-poor settings. However, based on a qualitative and quantitative
      study of a class of 38 PHC nurses, this paper emphasises that the nurses are
      women and men first--and as such, experience the same cultural values, and
      indeed, similar or higher levels of violence, as the clients they are expected to
      counsel and treat. Current models for encouraging nurses and other health care
      workers to detect and address gender-based violence have evolved largely in the
      context of developed countries, and have focused primarily on acquiring the
      knowledge, skills and attitudes necessary to engage this issue in the health care
      setting. Yet, as this paper suggests, there is an urgent need to understand and
      address the lived experiences of the nurses, and the duality of their roles as
      professionals and as community members, before promoting the training of nurses
      as an effective strategy for dealing with gender-based violence. One such
      training model was piloted and assessed in this study. The intervention used
      partnership with a domestic violence NGO to initially focus on dealing with the
      attitudes and experiences of the nurses as individuals, and to begin a process of
      self-awareness and sensitisation. Only then did the intervention turn to their
      roles as professional nurses. Clearly, there is a need for further research to
      explore these issues in more depth and to inform the development of appropriate
      training strategies for health care workers, particularly in developing
      countries. Moreover, such research may well have implications for the design and
      implementation of training interventions aimed at raising awareness and capacity
      within other sectors such as the welfare, police and judicial systems.

PMID- 11989961
TI  - Health sector reform and public sector health worker motivation: a conceptual
      framework.
AB  - Motivation in the work context can be defined as an individual's degree of
      willingness to exert and maintain an effort towards organizational goals. Health
      sector performance is critically dependent on worker motivation, with service
      quality, efficiency, and equity, all directly mediated by workers' willingness to
      apply themselves to their tasks. Resource availability and worker competence are
      essential but not sufficient to ensure desired worker performance. While
      financial incentives may be important determinants of worker motivation, they
      alone cannot and have not resolved all worker motivation problems. Worker
      motivation is a complex process and crosses many disciplinary boundaries,
      including economics, psychology, organizational development, human resource
      management, and sociology. This paper discusses the many layers of influences
      upon health worker motivation: the internal individual-level determinants,
      determinants that operate at organizational (work context) level, and
      determinants stemming from interactions with the broader societal culture. Worker
      motivation will be affected by health sector reforms which potentially affect
      organizational culture, reporting structures, human resource management, channels
      of accountability, types of interactions with clients and communities, etc. The
      conceptual model described in this paper clarifies ways in which worker
      motivation is influenced and how health sector reform can positively affect
      worker motivation. Among others, health sector policy makers can better
      facilitate goal congruence (between workers and the organizations they work for)
      and improved worker motivation by considering the following in their design and
      implementation of health sector reforms: addressing multiple channels for worker
      motivation, recognizing the importance of communication and leadership for
      reforms, identifying organizational and cultural values that might facilitate or
      impede implementation of reforms, and understanding that reforms may have
      differential impacts on various cadres of health workers.

PMID- 11989962
TI  - Researching Aboriginal health: experience from a study of urban young people's
      health and well-being.
AB  - European colonisation had a devastating effect on the health and well-being of
      indigenous people in Australia. The history of Aboriginal health research has
      reflected the history of colonisation; research has understandably been viewed
      with distrust. The need for accurate statistics and improved understanding of
      health problems is clear, but obtaining them is not easy. In this paper we
      describe the first stage of a study of the health and well-being of urban young
      people that was initiated and carried out by the Victorian Aboriginal Health
      Service (VAHS), a community controlled organisation. This longitudinal study aims
      to describe the prevalence and incidence of a range of health problems, to
      explore their interrelated determinants, and to increase the capacity of the VAHS
      to carry out research. The process of planning and carrying out this study raised
      a number of interesting ethical, cultural and methodological issues. These issues
      include the establishment of an appropriate and properly constituted local ethics
      committee, the difficulty of obtaining a representative sample, the need for
      ongoing negotiation, attention to language, the use of a subject-generated
      identity code, and the need to recruit a wide range of peer interviewers.
      Achievements include a series of community reports of the findings, the
      establishment of a cohort of young people for a longitudinal study; a shift in
      attitudes toward research; a strengthened network of young Kooris; increased use
      of the health service by young people and the establishment of an after-hours
      clinic service and meeting place for young people. The aim of this analysis of
      our achievements and constraints is to assist others planning similar research,
      and to demonstrate the value for process and outcomes of research conducted under
      Aboriginal community control.

PMID- 11989963
TI  - Depression, parenthood, and age at first birth.
AB  - This study tests the hypothesis that the correlation between current depression
      and parenthood depends on the age at first birth for adults. An early first birth
      suggests a poor start in life. It may reflect a disordered transition from
      adolescence into adulthood and may itself disrupt that transition, with life long
      consequences that influence emotional well-being. To test the hypothesis we
      analyze data from a 1995 survey of 2592 US adults 18 through 95. Among the
      parents we find a generally negative association between age at first birth and
      recent feelings and signs of depression, adjusting for age, sex, minority status,
      and education of the respondent's parents. Respondents who had a first birth
      before age 23 report more feelings and signs of depression than do nonparents;
      those who had a first birth after age 23 report fewer than do nonparents. The
      association between depression and age at first birth is monotonic for males but
      parabolic for females. The age at first birth associated with the lowest
      predicted depression for females is around 30. Regression analyses indicate that
      several correlates account for the apparent psychological benefits of delaying
      first birth: later first marriages, higher educational attainment, lower risk of
      having had a prolonged period needing a job but not being able to find one, lower
      risk of having had periods lacking the money for household necessities, and
      better current physical health. For women, health consequences limit the
      emotional benefits of prolonged delay of the first birth.

PMID- 11989964
TI  - Household economic strategies and nutritional anthropometry of women in American
      Samoa and highland Bolivia.
AB  - This study compares findings from research projects involving different genetic,
      environmental, and cultural contexts: a study of lifestyle and health from
      American Samoa (ASLS) and the Bolivian project. Reproduction and Ecology in
      Provincia Aroma (REPA). This paper presents analyses of varying economic
      strategies and their association with nutritional status indicators in each
      population. The ASLS sample includes 66 Samoan women and the REPA sample includes
      210 Aymara women. Principle components analysis of household economic resources
      within each sample extracted two significant factors: one represents modernizing
      influences including education and occupational status, and the other represents
      ethnographically salient traditional economic behavior. The traditional pattern
      includes adding household members in Samoa and selling agricultural products in
      Bolivia. This analysis places each woman along two continua, traditional and
      modern, based on her household mobilization of economic resources, permitting an
      understanding of the patterns underlying household economic behavior that is not
      possible in univariate analyses of socioeconomic variables. For the Bolivian
      women the strategy involving more education and higher occupational status was
      associated with higher measures of several nutritional status indicators,
      including body mass index, arm muscle area, and peripheral skinfolds. But among
      the Samoan women, where substantial obesity was the norm, there were no
      significant differences in anthropometric measurements based on economic
      strategies. These data argue for the importance of directly measuring the
      potential consequences of variation in household economic strategies rather than
      merely inferring such, and of assessing ethnographically relevant aspects of
      household economic production rather than limiting analyses to non-context
      specific economic indicators such as income. This focus on household strategy is
      likely to be fruitful especially where economic and nutritional conditions are
      marginal. The findings from Bolivia also support efforts in developing countries
      to improve girls' education, and thereby occupational prospects, as a means to
      improve their health status as women.

PMID- 11989965
TI  - GABA in the endocrine pancreas: cellular localization and function in normal and
      diabetic rats.
AB  - Gamma amino butyric acid (GABA) and its related enzymes have been demonstrated in
      pancreatic beta cells of normal rat. Antibodies against GABA-synthesizing enzymes
      have been implicated in the pathogenesis of Type I diabetes. In spite of the
      importance of GABA in the aetiology of diabetes mellitus, detailed morphological
      data on the pattern of distribution of GABA in the pancreas of normal and
      diabetic rats are lacking. Diabetes mellitus (DM) was induced by a single dose of
      streptozotocin (STZ) given intraperitoneally (60 mg kg body weight(-1)). Four
      weeks after the induction of DM, normal (n = 6) and diabetic (n = 6) rats were
      anesthetized with chloral hydrate and their pancreata were removed and processed
      for the localization and effect of GABA on insulin secretion using
      immunohistochemistry and radioimmunoassay techniques. The number of GABA-like
      immunoreactive (GABA-LIR) cells in the pancreatic islets of STZ-diabetic rats
      decreased significantly (P<0.0001) when compared to non-diabetic control rats.
      The pattern and percentage distribution of GABA in the islet of Langerhans of
      normal and diabetic rat was similar to that of insulin. GABA induced a
      significant (P<0.0007) increase in insulin secretion from the pancreas of normal
      rats. In diabetic pancreas, GABA evoked a higher but not significant (P<0.1)
      increase in insulin secretion. These findings showed that the number of GABA-LIR
      cells is reduced significantly in diabetes. Moreover, GABA is a strong
      secretagogue of insulin from the pancreas of normal rat.

PMID- 11989966
TI  - Development of larval and transformed teeth in Ambystoma mexicanum (Urodela,
      Amphibia): an ultrastructural study.
AB  - Odontogenesis of early larval non-pedicellate teeth, late larval teeth with a
      more or less distinct dividing zone and fully transformed pedicellate teeth in
      Ambystoma mexicanum (Urodela) was studied to obtain insights into the development
      of differently structured teeth in lower vertebrates. Using transmission electron
      microscopy we investigated five developmental stages: (1) papilla; (2) bell stage
      (secretion of the matrix begins); (3) primordium (mineralization and activity of
      ameloblasts starts); (4) replacement tooth (young, old); and (5) established,
      functional tooth. Development of the differently structured teeth is largely
      identical in the first three stages. Mineralization takes place in apico-basal
      direction up to the (prospective) pedicel (early and some late larvae) or up to
      the zone that divides the late larval and transformed tooth in pedicel and
      dentine shaft (pedicellate condition). Mineralization starts directly at the
      collagen and by means of matrix vesicles. First odontoblasts develop small
      processes that extend to the basal lamina of the inner epithelial layer of the
      enamel organ. The processes are small and lack organelles in early larval teeth,
      but become larger, arborescent, and contain some organelles in late larval and
      transformed teeth. The processes are surrounded by unmineralized matrix
      (predentine). Odontoblasts at the basis of the teeth, at the pedicel, and in the
      zone of division do not develop significant cytoplasmic processes that extend
      into the matrix. Cells of the inner enamel epithelium differentiate to
      ameloblasts that secrete the enamel. In the early larval tooth they show an
      extensive basal labyrinth that becomes regressive when the enamel layer is
      completed. In late larval and transformed teeth, however, a large cavity arises
      between the basal ruffled border of ameloblasts and their basal lamina. This
      cavity appears to mediate amelogenesis. A small apical zone in early, but not in
      late larval teeth directly below the thin enamel layer consists of enameloid and
      is free of dentine channels.

PMID- 11989967
TI  - Expression of B-cell translocation gene 2 protein in normal human tissues.
AB  - The antiproliferative B-cell translocation gene 2 (BTG2(TIS21/PC3)) is emerging
      as an important regulator of cell cycle dynamics. BTG2(TIS21/PC3) expression
      increases in response to the induction of DNA damage, cell differentiation, cell
      quiescence, cell contact, and as part of a positive feedback mechanism in
      response to growth stimulation. The objective of the present study was to provide
      further insight into the biological function of BTG2(TIS21/PC3) by determining
      the expression levels and cellular localization of BTG2(TIS21/PC3) in a spectrum
      of normal human tissues and to determine the proliferative indices (based on Ki
      67 staining) and apoptotic indices (based on TUNEL assay) in those cell
      populations where BTG2(TIS21/PC3) was differentially expressed. Highest levels of
      BTG2(TIS21/PC3) expression were seen in kidney proximal tubules, lung alveolar
      bronchial epithelium and in the basal cell layer of prostate acini.
      BTG2(TIS21/PC3) was expressed at significantly different levels within the
      different epithelial populations of the kidney (proximal vs distal tubules) and
      prostate (acinar basal cells vs lumenal cells). Moderate levels of expression
      were seen in the acinar cells of breast and pancreas and in the mucosal
      epithelium of the intestine. Low levels of expression were seen in neurons,
      hepatocyctes, the zona granulosa of the ovary, round spermatids and thyroid
      follicles. Our results therefore indicate an imperfect correlation between the
      terminally differentiated phenotype and BTG2(TIS21/PC3) expression, but no
      correlation between basal cellular proliferative or apoptotic indices and
      BTG2(TIS21/PC3) expression levels.

PMID- 11989968
TI  - Hydroxyl free radicals induce cell differentiation in SK-N-MC neuroblastoma
      cells.
AB  - The SK-N-MC cell line is frequently used as a model of neuronal differentiation
      induced by 5-bromodeoxyuridine (BrdU). In this study, the differentiation
      properties of this cell line were investigated under hydroxyl free radical
      generation, and compared to BrdU treatment. Hydroxyl free radicals were generated
      in the cultures by the Fenton reaction, i.e. by simultaneous addition of ADP-Fe2+
      complex and H2O2. Microscopic morphological signs, as well as the
      acetylcholinesterase and ganglioside sialidase activities were considered as
      markers of neuronal differentiation of this cholinergic neuroblastoma cell line.
      Apart from the altered morphological appearance, the marker enzymes displayed
      significant increases after both types of intervention. We suggest that hydroxyl
      free radicals can induce in vitro cell differentiation. They apparently play a
      more complex role in cell physiology than simply causing oxidative damage.

PMID- 11989969
TI  - Spermatozoan morphology of four species of bivalve (Heterodonta, Veneridae) from
      Taiwan.
AB  - Using transmission and scanning electron microscopy, the mature spermatozoa of
      four bivalves of the family Veneridae--Gafrarium tumidum and Circe scripta
      (Circinae), Pitar sulfureum (Pitarinae) and Gomphina aequilatera (Tapetinae)--are
      described for the first time and compared with those of other bivalves,
      particularly other heterodonts. As our observations show, the spermatozoa of
      these four species are of the primitive type or ect-aquasperm form. The head
      contains a slightly curved nucleus with a short cone-shaped acrosome. The
      structure of the acrosome is typical of heterodont bivalves and two major
      components of the acrosomal vesicle material can be distinguished. The midpiece
      exhibits four or five mitochondria which surround the proximal and the distal
      centrioles. Variation in the shape and dimensions of the acrosomal vesicle and
      nucleus is substantial in these four Veneroidea species.

PMID- 11989970
TI  - Human periodontal ligament cells derived from deciduous teeth induce
      osteoclastogenesis in vitro.
AB  - The receptor activator of NF-kappa B ligand (RANKL) and its decoy receptor,
      osteoprotegerin (OPG), are the important proteins involved in osteoclastogenesis.
      In this study, we investigated the expressions of RANKL and OPG in cultured human
      periodontal ligament cells derived from deciduous teeth (DPDL cells) and their
      roles in osteoclastogenesis. Northern blotting revealed that the OPG mRNA was
      down-regulated by application of 10(-8) M 1 alpha, 25(OH)2 vitamin D3 [1,25
      (OH)2D3] and 10(-7) M dexamethasone (Dex). In contrast, RANKL mRNA was up
      regulated by the same treatment. Western blotting demonstrated a decrease in OPG
      following application of 1, 25-(OH)2D3 and Dex. Tartrate-resistant acid
      phosphatase (TRAP)-positive multinuclear cells (MNCs) were induced when DPDL
      cells were co-cultured with mouse bone marrow cells in the presence of 1,25
      (OH)2D3 and Dex. TRAP-positive MNCs increased significantly when the DPDL cells
      were co-cultured with bone marrow cells in the presence of anti-human OPG
      antibody together with 1, 25-(OH)2D3 and Dex. These results indicate that PDL
      cells derived from deciduous teeth synthesize both RANKL and OPG and could
      regulate the differentiation of osteoclasts.

PMID- 11989971
TI  - Kinetics of spermatogenesis in the Mongolian gerbil (Meriones unguiculatus).
AB  - The Mongolian gerbil (Meriones unguiculatus) is a small rodent native to the arid
      regions of Mongolia and Northeastern China. The present study provides
      descriptions of both the cellular associations of the seminiferous-epithelium
      cycle and relative frequencies of stages in the gerbil. Based on the development
      of the acrosomic system and the nuclear morphology changes using the PAS-H
      staining technique, the transformation of spermatids into spermatozoa was divided
      into 15 steps. The first 12 steps were used to identify 12 stages or cellular
      associations and the other three steps were spread among the first six stages of
      the cycle of the seminiferous epithelium. The relative frequencies found for
      stages I through XII were: 13.15; 8.06; 8.98; 6.48; 5.37; 6.71; 7.36; 7.45; 7.27;
      5.83; 11.53 and 11.81, respectively. Stage I had the highest frequency while
      stage V proved the lowest frequency among the XII stages. The pattern of
      spermatogenesis is similar to those of rodents used as laboratory animals. The
      present description is the first for this rodent and provides the foundation for
      a variety of future studies of the testis in this animal.

PMID- 11989972
TI  - Biomedical significance of endothelial cell specific growth factor, angiopoietin.
AB  - Until recently, vascular endothelial growth factor (VEGF) was the only growth
      factor proven to be specific and critical for blood vessel formation. Other long
      known factors, such as the fibroblast growth factors (FGFs), platelet-derived
      growth factor, or transforming growth factor-beta, had profound effects in
      endothelial cells. But such factors were nonspecific, in that they could act on
      many other cells, and it seemed unlikely that these growth factors would be
      effective targets for treatment of endothelial cell diseases. A recently
      discovered endothelial cell specific growth factor, angiopoietin, has greatly
      contributed to our understanding of the development, physiology, and pathology of
      endothelial cells (Davis et al., 1996; Yancopoulos et al., 2000). The recent
      studies that identified and characterized the physiological and pathological
      roles of angiopoietin have allowed us to widen and deepen our knowledge about
      blood vessel formation and vascular endothelial function. Therefore, in this
      review, we describe the biomedical significance of these endothelial cell growth
      factors, the angiopoietins, in the vascular system under normal and pathological
      states.

PMID- 11989973
TI  - The stimulatory effect of IL-1beta on the insulin secretion of rat pancreatic
      islet is not related with iNOS pathway.
AB  - Interleukin 1 (IL-1) is a pleiotropic cytokine with the potential to destroy
      pancreatic beta-cells, and thought to be involved in the pathogenesis of type I
      diabetes mellitus. Expression of inducible nitric oxide synthase (iNOS) and
      subsequent NO formation induced by IL-1beta may impair an islet function in
      rodents. Inhibition of iNOS may protect against cytokine-induced beta-cell
      suppression, although cytokines might also induce NO-independent impairment. To
      examine the role of NO in the IL-1beta treated cells, rat islets were treated
      with various concentrations (0, 0.5, 5, 50, 500 pmol/L) of IL-1beta with or
      without NG-monomethyl-L-arginine (NMMA; a competitive inhibitor of nitiric oxide
      synthase) for 2 or 6 h. Insulin secretion was stimulated in islets treated with
      5, 50, and 500 pmol/ L of IL-1beta for 2 h and 0.5 pmol/L for 6 h, respectively.
      The stimulatory effect of IL-1beta on the insulin secretion of rat islets was not
      prevented by NMMA. Nitrate concentration was increased in a time- and
      concentration-dependent manner. Nitrate production was inhibited by NMMA. iNOS
      mRNA expression was increased at concentrations more than 5 pmol/L of IL-1beta in
      a dose dependent manner. iNOS mRNA was detectable after 2 h and peaked at 6 h but
      decreased after 24 h. These results suggested that the stimulatory effect of IL
      1beta on the insulin secretion of rat islets is independent of iNOS-related NO
      production of IL-1beta and the enzyme activity of nitric oxide synthase.

PMID- 11989974
TI  - Alterations of HLA class I and class II antigen expressions in borderline,
      invasive and metastatic ovarian cancers.
AB  - In an effort to understand whether HLA class I and II plays any role in the
      process of tumorigenesis and metastasis, we have immunohistochemically examined
      expression of HLA class I and II antigen by using the monoclonal antibodies (mAb)
      L368 (for beta2m of HLA class I), HC-10 (for HLA-B, C heavy chains), and LGII
      612.14 (for HLA class II heavy chain) in 5 borderline serous malignancy (BSM), 20
      serous adenocarcinomas (SA), 15 borderline mucinous malignancy (BMM), and 10
      mucinous adenocarcinomas (MA) of human ovary tumor case tissues. In BSM, the
      distribution and intensity of HLA expressions failed to reach statistical
      significance. In SA, HLA class I beta2-microglobulin (beta2m), HLA-B, C heavy
      chains and HLA class II heavy chain antigen expressions were down-regulated.
      Although expressions of HLA-B, C heavy chains and class II heavy chain were down
      regulated in metastatic SA, there were no differences in HLA expression levels
      between primary and metastatic lesions. In BMM, class II heavy chain expressions
      were down-regulated. In MA, beta2m, HLA-B, C heavy chains and class II heavy
      chain expressions were also down-regulated. Thus, we could distinguish the
      reduction or absence of HLA molecule expression was related to malignant
      potential. Loss of HLA class I and II molecules in invasive ovarian cancers
      raises the possibility that this could be a factor for tumor cells to retain
      invasiveness.

PMID- 11989975
TI  - Differential modulation of zinc-stimulated p21(Cip/WAF1) and cyclin D1 induction
      by inhibition of PI3 kinase in HT-29 colorectal cancer cells.
AB  - Activation of the extra cellular signal regulated kinase (ERK) pathway is
      involved in both proliferation and growth arrest of cells depending on intensity
      and duration of stimuli. In this study, we have elucidated differential
      regulation of the zinc-stimulated p21(CiP/WAF1) and cyclin D1 activation by
      inhibition of phosphoinositide 3-kinase (PI3K). In HT-29 colorectal cancer cells,
      the ERK activities were increased by zinc, which was accompanied by the induction
      of p21(Cip/WAF1) and cyclin D1. However, in the HT-29 cells pre-treated with PI3K
      inhibitor, LY294002, zinc induced further the p21(CiP/WAF) induction whereas
      abrogated cyclin D1 induction. In addition, the induction of p21(Cip/WAF1)
      expression completely inhibited the incorporation of bromodeoxyuridine (BrdU)
      into the nucleus, indicating that p21(CiP/WAF1) is an important indicator for ERK
      dependent growth arrest. These studies suggest presence of an inter-related
      regulatory mechanism of cell proliferation by ERK and PI3K pathways.

PMID- 11989976
TI  - D4-GDI is cleaved by caspase-3 during daunorubicin-induced apoptosis in HL-60
      cells.
AB  - Daunorubicin, an anti-cancer drug, is known to induce apoptosis in HL-60 cells in
      a dose-dependent manner through the activation of caspase-3 (CPP32). Caspase-3
      selective inhibitor, Ac-DEVD-CHO, prevented both the activation of caspase-3 and
      cleavage of poly(ADP-ribose) polymerase (PARP). D4-GDI is a GDP dissociation
      inhibitor for the Ras-related Rho family GTPase in hematopoietic cells. Here we
      report that D4-GDI is a substrate for the caspase-3. D4-GDI was cleaved to a 23
      kDa fragment by daunorubicin treatment in HL-60 cells with kinetics that parallel
      the onset of apoptosis. D4-GDI cleavage as well as DNA fragmentation was
      inhibited by treatment with Ac-DEVD-CHO but not with Ac-YVAD-CHO, a caspase-1
      inhibitor. These data suggest that D4-GDI of Rho family GTPase may be regulated
      during apoptosis through the caspase-3 mediated cleavage of the GDI protein.

PMID- 11989977
TI  - The p38 mitogen-activated protein kinase is involved in stress-induced
      phospholipase D activation in vascular smooth muscle cells.
AB  - Oxidative stress has been implicated in mediation of vascular disorders. Earlier
      study showed that the exposure of vascular smooth muscle cells (VSMC) to
      pervanadate (hydrogen peroxide plus orthovanadate) resulted in the accumulation
      of [3H]phosphatidylbutanol. In this study, the effect of pervanadate on the
      activation of p38 mitogen-activated protein kinase (p38 MAPK) was studied in the
      VSMC. Pervanadate treatment activated p38 MAPK in a dose-and time-dependent
      manner. Interestingly, specific inhibition of p38 MAPK with SB203580 attenuated
      pervanadate-induced PLD activation. This correlates with the finding that
      expression of dominant negative mutants of MKK3/6 inhibited the PLD activation.
      SB203580 pretreatment also inhibited other cellular stressors (i.e. high
      osmolarity and UV light)-induced PLD activation. The possible correlationship of
      p38 MAPK activation with PKC was examined since PKC is reported to be involved in
      the pervanadate-induced PLD activation. Calphostin C, a PKC inhibitor, suppressed
      pervanadate-induced p38 MAPK and PLD activation in a dose-dependent manner. These
      results suggest that PKC-p38 MAPK may represent an upstream pathway of PLD in the
      signal transduction of cellular stress.

PMID- 11989978
TI  - Aspartate modulates the ethanol-induced oxidative stress and glutathione
      utilizing enzymes in rat testes.
AB  - In order to develop a preventive strategy against ethanol-induced oxidative
      damages on various tissues and organs, we have examined the protective effect of
      aspartate on the pathogenesis of testes in the ethanol treated animals. Adult
      male Sprague-Dawley rats were given ethanol in an amount of 36% of total calories
      via Lieber-DeCarli liquid diet for 6 weeks without or with aspartate (2 mM in the
      diet). The control group was pair-fed the diet containing isocaloric dextrin
      maltose instead of ethanol. The pathogenesis of testes at post- 6 weeks of
      experiments were carried out by histochemistry and biochemical parameters for
      oxidative stress such as the level of thiobarbituric acid reactive substances
      (TBARS) and the activities of glutathione utilizing enzymes were also examined.
      Chronic ethanol administration resulted in the increased amount of thiobarbituric
      acid reactive substances (TBARS) in the testes, which was significantly lessened
      by concurrent aspartate treatment (p < 0.05). In addition to this, liver function
      test indicated by alkaline phosphatase activity in serum showed that the ethanol
      induced hepatotoxicity was significantly ameliorated by aspartate administration.
      And the activities of glucose-6-phosphate dehydrogenase and glutathione
      transferase in testis cytosol were decreased in the ethanol treated rats (p <
      0.01 and < 0.005, respectively). These data suggest that aspartate may attenuate
      the ethanol-induced oxidative tissue damage in rat testes possibly through a
      redox-related protective effect on peroxidation.

PMID- 11989979
TI  - Enhanced expression of neuronal nitric oxide synthase and phospholipase C-gamma1
      in regenerating murine neuronal cells by pulsed electromagnetic field.
AB  - Pulsed electromagnetic field (PEMF) has been shown to improve the rate of
      peripheral nerve regeneration. In the present study we investigated the
      expression of neuronal nitric oxide synthase (nNOS) and phospholipase C-gamma1
      (PLC-gamma1) in regenerating rat laryngeal nerves during the exposure to PEMF
      after surgical transection and reanastomosis. Axons were found to regenerate into
      the distal stump nearly twice faster in PEMF-exposed animals than in the control.
      Consistently, motor function was better recovered in PEMF-treated rats. The
      expression of nNOS and PLC-gamma1 was highly enhanced in the regenerated nerves.

PMID- 11989980
TI  - Characterization of cis-acting elements in the rat ATP citrate-lyase gene
      promoter.
AB  - The cis-acting element in the promoter of the rat ATP-citrate lyase (ACL) and
      transcription factors which interact with these elements were determined. Six Sp1
      binding sites and CAAT box exist in the region from transcription start site to 
      419 bp which showed the highest promoter activity in ACL promoter previously. In
      the region from -612 to -419, C/EBP binding site and other protein binding sites
      were also detected. Chloramphenicol acetyltransferase assay of ACL promoter
      suggested that multiple Sp1 sites might be involved in the ACL transcription. Gel
      mobility shift assay with antibodies against Sp1 and Sp3 revealed that DNA
      binding efficiency of Sp1 is increased in the liver of rats re-fed low fat/high
      carbohydrate diet after fasting. These results suggest that Sp1 is one of the
      most important transcription factors for ACL promoter to produce basal and
      induced transcription by low fat/high carbohydrate diet.

PMID- 11989981
TI  - Expression of aquaporin-5 and its regulation in skeletal muscle cells.
AB  - The aquaporins constitute a family of homologous intrinsic membrane proteins that
      function as highly selective water channels and are highly expressed in tissues
      where rapid water movement across the cell membrane is required. Molecular
      mechanism of water transport through the plasma membrane of skeletal muscle is
      still not clear. This study was designed to identify aquaporin subtypes and their
      expression regulation in C2C12 cells, a mouse myoblastic cell line. RT-PCR,
      immunohistochemistry and Western blot analysis revealed that C2C12 cells express
      AQP5. AQP5 expression was increased by induction of C2C12 differentiation.
      Exposure of C2C12 cells to hypertonic solutions induced an increase in AQP5
      expression and p38 kinase activation. However, a p38 kinase inhibitor failed to
      inhibit hyperosmolar induction of AQP5 expression in C2C12 cells. These data
      indicate that skeletal muscle cells express AQP5 protein and its expression is
      regulated by differentiation and hypertonic stress.

PMID- 11989982
TI  - Expression of integrins, cyclooxygenases and matrix metalloproteinases in three
      dimensional human endometrial cell culture system.
AB  - The objective of this investigation was to establish a three-dimensionally
      cultured human endometrium which could be used as a tissue model for the
      mechanism study of implantation in vitro. By using human endometrial stromal (ES)
      and epithelial cells (EE) from hysterectomy specimens, reconstruction of
      endometrium in culture was established by first layering a collagen gel
      containing ES cells, then overlaying with the Matrigel containing endometrial
      epithelial (EE) cells. Ultrastructural examination of the 48 h-endometrial cell
      culture revealed monolayered columnar EE cells with microvilli on the collagen
      layer containing ES cells and appearance of the tight junctions and desmosomes
      between EE cells, a cell layer closely resembling the native endometrium.
      Immunohistochemical characterization of the reconstructed endometrium showed a
      strong immunoreactivity for cytokeratin, integrin alpha1, alpha4 and beta3
      subunits, cyclooxygenases-1 and -2, matrix metalloproteinases-1, -2, -3 and -9,
      and tissue inhibitor of metalloproteinases-1 and -2 in the EE cells comparable to
      the native endometrial epithelium. ES cells also showed stronger immunoreactivity
      for cyclooxygenases, integrins and MMPs, but less for cytokeratin. Gelatin
      zymographic analyses of the media obtained from the reconstructed endometrium
      model showed gelatinase activity bands at 57, 60, 72, 92 and 97 kDa molecular
      weight, respectively. The present study provides a possibility that our three
      dimensionally cultured endometrium model could mimic the morphological and
      functional characteristics of the native endometrium. The model could be used to
      clarify the roles of various molecules involved in the human implantation.

PMID- 11989983
TI  - Effects of chlorinated aliphatic hydrocarbons on the fidelity of cell division in
      human CYP2E1 expressing cells.
AB  - Chlorinated organic chemicals are widely used in industry and are present in the
      environment. Five chlorinated aliphatic hydrocarbons, namely 1-2-dichloroethane,
      1,1,2-trichloroethane, trichloroethylene, 2,3-dichlorobutane and 1-chlorohexane
      were investigated to determine their influence upon the fidelity of cell division
      in cultured mammalian cells. In order to determine the influence of these
      chemical compounds upon the fidelity of cell division, a technique known as
      differential staining of chromosomes and spindle was performed with one
      genetically engineered cell line and its parental cell line. The genetically
      engineered cell line used in this study expressed a human P450 enzyme, CYP2E1.
      Four chemicals, 1-2-dichloroethane, trichloroethylene, 2,3-dichlorobutane and 1
      chlorohexane required metabolic bioactivations in order to induce spindle damage
      in cultured mammalian cells whereas 1,1,2-trichloroethane was a direct-acting
      spindle poison.

PMID- 11989984
TI  - The functional domains of dopamine transporter for cocaine analog, CFT binding.
AB  - Cocaine analogue, CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) binding
      to dopamine transporter (DAT) in different species is quite heterogeneous. CFT is
      scarcely detected in bovine DAT whereas it is conspicuous in humans. To examine
      the structural basis for this functional discrepancy, we analyzed transporter
      chimeras of these two DATs. The CFT binding activities are avid in all of the
      chimeric DATs of which both of the 3rd and the 6-8th transmembrane domain (TM)
      are composed of human DAT sequences. On the contrary, CFT binding activities were
      scarcely detected if either or both of two regions are replaced with bovine
      sequences. These findings indicate that the CFT binding absolutely requires human
      DAT sequences, at least, in the regions encompassing the 3rd and 6-8th
      transmembrane domain (TM), and that these regions might contribute to form the 3
      dimensional pocket for CFT binding.

PMID- 11989985
TI  - Home treatment for mental health problems: a systematic review.
AB  - BACKGROUND: Concerns have been raised about the scope and generalizability of
      much community mental health research. In particular, both experimental and
      control services are poorly characterized. METHODS: To review the effectiveness
      of 'home treatment' for mental health problems in terms of hospitalization, we
      conducted a systematic review, using Cochrane methodology but with a wider remit.
      Non-randomized studies were included in response to concerns about RCTs'
      generalizability. All authors were followed up for data on service components.
      'Home treatment' was defined broadly for the purposes of the literature search,
      but included studies were then assessed against service components specifically
      focused on delivering treatment at home. The study tested components and other
      features for associations with days in hospital, as well as conducting a
      conventional meta-analysis of data on days in hospital. RESULTS: We found 91
      studies, 18 comparing home to in-patient treatment. Sixty per cent of authors
      responded to follow-up. The vast majority of the services studied had a 'home
      treatment function' and regularly visited patients at home. The heterogeneity of
      control services made meta-analysis problematical as did the limited availability
      of data. There was some evidence that 'regular' home visiting and combined
      responsibility for health and social care were associated with reduced
      hospitalization. The inclusion of non-randomized studies rarely affected the
      findings. CONCLUSIONS: Evidence concerning the effectiveness of home treatment
      remains inconclusive. A centrally coordinated research strategy is recommended,
      with attention to study design. Experimental and control service components
      should be prospectively recorded and reported to enable meaningful analysis.

PMID- 11989986
TI  - Heavy users of acute psychiatric beds: randomized controlled trial of enhanced
      community management in an outer London borough.
AB  - BACKGROUND: Heavy users of psychiatric services, often defined as the population
      that uses the most beds, consume a large part of the resources used by the whole
      service, despite being relatively small in number. Any intervention that reduces
      heavy use is therefore likely to lead to significant savings, and enhancement of
      standard care using a form of intensive case management akin to assertive
      community treatment was thought to be a pragmatic strategy for testing in this
      group. METHODS: The effectiveness of enhanced community management (ECM) was
      compared with standard care alone in heavy users, who represented the 10% of
      patients with the highest number of hospital admissions and occupied bed days
      over the previous 6.5 years in an outer London borough. One hundred and ninety
      three patients were randomly assigned to ECM or standard care and their use of
      services was determined after 1 and 2 years, with assessments of costs, clinical
      symptoms, needs, and social function made before entry into the study and after 1
      and 2 years. RESULTS: Despite a 24 fold increase in community contacts in the
      study group, there were no significant differences between the two groups in any
      of the main outcome measures. Small savings on in-patient and day-hospital
      service costs were counterbalanced by the increased costs of outpatient and
      community care for the subjects assigned to ECM. Clinical outcome data derived
      from interviews in two-thirds of the subjects were similar in both groups.
      CONCLUSIONS: Providing additional intensive community focused care to a group of
      heavy users of psychiatric in-patient services in an outer London borough does
      not lead to any important clinical gains or reduced costs of psychiatric care.

PMID- 11989987
TI  - The neuropsychology of antisocial personality disorder.
AB  - BACKGROUND: The literature on executive function in antisocial populations is
      unclear due to variation in diagnostic criteria and variation in the inclusion of
      healthy control comparison groups. Some studies suggest prototypical psychopathy
      is associated with specific deficits in ventromedial prefrontal (VMPFC) function
      rather than dorsolateral prefrontal (DLPFC). Meta-analytical studies, however,
      suggest that antisocial personality disorder may be associated with a broader
      range of executive deficits. This study assessed DLPFC and VMPFC function in
      antisocial personality disorder subjects and controls using the Cambridge
      Neuropsychological Test Automated Battery (CANTAB) and a Go/NoGo task
      respectively. METHODS: All subjects were screened for Axis I pathology, substance
      misuse and prescribed medication. The performance of 29 subjects with antisocial
      personality disorder DSM-IV and 20 male right-handed controls (matched for age
      and IQ) on the neuropsychological test battery was compared. RESULTS: Subjects
      with antisocial personality disorder displayed impairments on DLPFC executive
      function tasks of planning ability and set shifting. Impairments were also seen
      in VMPFC Go/NoGo tasks and in visual memory tasks. CONCLUSIONS: Antisocial
      personality disorder is associated with a broad range of deficits in DLPFC and
      VMPFC function. Future studies need to examine relationships between the
      interpersonal and behavioural components of antisocial personality disorder and
      neuropsychological function.

PMID- 11989988
TI  - Visuospatial memory and learning in first-episode schizophreniform psychosis and
      established schizophrenia: a functional correlate of hippocampal pathology?
AB  - BACKGROUND: Despite a number of studies that have indicated impaired memory
      function in patients with schizophrenia, there have been few that have used a
      sensitive measure of right medial temporal lobe pathology. Given the reported
      findings of reduced hippocampal volume in schizophrenia, we used a theoretically
      sensitive test of the right medial temporal lobe to determine the nature of the
      visuospatial memory deficit in the disorder. METHODS: Seventy-six patients (37
      with a first-episode schizophreniform psychosis, and 39 with established
      schizophrenia) were compared with 41 comparison subjects on a number of tests of
      visuospatial memory. These included spatial working memory, spatial and pattern
      recognition memory and a pattern-location associative learning test. RESULTS:
      Both patient groups displayed recognition memory deficits when compared to the
      comparison group. However, only those patients with established schizophrenia (of
      9 years duration on average) were impaired on the associative learning test.
      CONCLUSIONS: The results indicate either a progressive decline in visuospatial
      associative learning ability over the course of the disorder, or that poor
      visuospatial associative learning is a marker for poor prognosis. In addition,
      these results have implications for our understanding of the role of the right
      medial temporal lobe in the pathophysiology of schizophrenia.

PMID- 11989989
TI  - Reversed lateralization of temporal activation during speech production in
      thought disordered patients with schizophrenia.
AB  - BACKGROUND: Formal thought disorder is a core symptom of schizophrenia. It is
      associated with a reversed lateralization of the superior temporal cortex volume,
      an area that is implicated in lexical retrieval. We investigated the neural
      correlates of word retrieval during continuous speech in patients with formal
      thought disorder using functional magnetic resonance imaging (fMRI). METHODS:
      Blood oxygenation level dependent (BOLD) contrast was measured with fMRI while
      six patients with schizophrenia and six healthy control subjects spoke about
      seven Rorschach inkblots for 3 min each. Subjects produced varying amounts of
      speech during each run. In a within subject design, the number of words produced
      was correlated with the BOLD contrast in the two runs in each participant who
      showed the highest variance of speech output. RESULTS: In control subjects, the
      amount of speech produced was mainly correlated with activation in the left
      superior temporal gyrus. In the patient group, the main correlations were in the
      right superior temporal gyrus. CONCLUSIONS: During the production of continuous
      speech, patients with formal thought disorder showed a reversed laterality of
      activation in the superior temporal cortex. This is consistent with findings of
      perturbed hemispheric interaction in schizophrenia, particularly in patients with
      formal thought disorder.

PMID- 11989990
TI  - Elasticity and confabulation in schizophrenic delusions.
AB  - BACKGROUND: This experiment examines two aspects of delusional cognition that
      have been reported clinically but not investigated empirically. These are the
      incorporation of potentially conflicting information into the recall of delusion
      related scripts and the type and amount of material produced additional to that
      presented for recall, referred to here as confabulation. METHODS: Three groups of
      patients--deluded schizophrenics, non-deluded schizophrenics and matched non
      psychiatric controls--were asked to recall two 15-item scripts, which comprised
      10 typical and five atypical components. It was hypothesized that deluded
      subjects whose delusion was relevant to one of the scripts would recall more of
      the atypical components of the script and would also be less likely to make
      script-atypical confabulations in the recall of this particular script. RESULTS:
      Recall was assessed for the amount and type of content remembered and the amount
      and type of confabulation. The results did not support the hypothesis that
      atypical items would be incorporated into the recall of delusion-relevant
      material. However, deluded subjects did retain their schema boundaries in the
      recall of script items relevant to their own delusion but were less able to
      adhere to a script framework in the recall of material unrelated to their
      delusion. CONCLUSIONS: These results are discussed within a schema specific
      account of delusions, which conceptualizes the delusion as an overused schema
      whose preferential use leads to a failure to develop other scripts but whose own
      contents remain well-defined.

PMID- 11989991
TI  - Different negative priming impairments in schizophrenia and subgroups of
      obsessive-compulsive disorder.
AB  - BACKGROUND: Inhibitory functioning is assumed to be deficient in some psychiatric
      disorders, most notably in patients with schizophrenia and obsessive-compulsive
      disorder (OCD). In order to investigate inhibitory functioning, priming tasks are
      commonly used. The present paradigm offers the opportunity to isolate specific
      distractor features (identity, location) for independent examination. METHODS:
      Negative priming (NP) for stimulus identity and location was examined in patients
      with schizophrenia (N = 16), patients with OCD (N = 15) and matched controls (N =
      16). All groups performed a referent size-selection task in which they were
      instructed successively to select the larger one of two cardinal numbers. The
      deeper processing of both stimuli was expected to yield large NP effects that
      allow the detection of subtle group differences. RESULTS: Large NP effects were
      found for stimulus identity in all three groups. Schizophrenic patients differed
      from normal controls with respect to the amount of incidental location priming.
      Subgroup analyses of OCD patients showed NP impairments for checkers when the
      response-stimulus interval (RSI) was short, but large identity NP when the RSI
      was long. OCD non-checkers showed normal NP patterns with short RSI, but reduced
      identity NP with longer RSI. CONCLUSIONS: Schizophrenic patients do not show the
      ability to use spatial selective attention in order to guide their actions as
      shown by normal controls. Information processing was differentially impaired in
      OCD subgroups (checkers and non-checkers) dependent on RSI variation. This result
      supports those studies that found reduced NP in OCD patients and points to the
      necessity of differential subgroup studies.

PMID- 11989992
TI  - Mood, eating behaviour and attention.
AB  - BACKGROUND: Obesity is a growing health problem, but most people find dieting
      unsuccessful. Three studies examine possible reasons for the difficulty and the
      extent to which dieting-related reductions in cognitive function are associated
      with mood and well-being. METHOD: In Study One, 49 female dieters were compared
      with a control group of 31 matched non-dieters on measures of well-being, mood,
      eating behaviour (Dutch Eating Behaviour Questionnaire), and attention. Study Two
      examined two measures of restraint to examine why previous studies find high
      restrainers are prone to react to emotion. Study Three experimentally manipulated
      mood using music and the standard Velten Induction Procedure to examine attention
      in restrainers and emotional eaters. RESULTS: Dieting was found to be associated
      with deficits in sustained attention. This finding was further supported by the
      demonstration of a significant impairment in performance following a negative
      mood induction in high emotional eaters whereas high restrainers were relatively
      unaffected by the mood challenge. CONCLUSIONS: We suggest that different aspects
      of eating behaviour have dissociable effects on cognitive-affective function.
      Trait tendencies to restrained eating are associated with attentional deficits,
      but are not further affected by mood disruption. It is the long-term tendency to
      eat when emotional that combines with current emotional state to trigger
      cognitive deficits.

PMID- 11989993
TI  - Early detection of isolated memory deficits in the elderly: the need for more
      sensitive neuropsychological tests.
AB  - BACKGROUND: Early detection of cognitive decline in the elderly is important
      because this may precede progression to Alzheimer's disease. The aim of this
      study was to see whether sensitive neuropsychological tests could identify pre
      clinical cognitive deficits and to characterize the cognitive profile of a
      subgroup with poor memory. METHODS: A neuropsychological test battery was
      administered to a community-dwelling sample of 155 elderly volunteers who were
      screened with CAMCOG at enrolment (mean age 74.7 years). The battery included
      tests of episodic memory. semantic and working memory, language and processing
      speed. RESULTS: Episodic memory test z scores below 1 S.D. from the cohort mean
      identified 25 subjects with non-robust' memory performance. This group was
      compared to the remaining 'robust memory' group with a General Linear Model
      controlling for age, IQ, education and gender. Test performance was significantly
      different in all tests for episodic and semantic memory, but not in tests for
      working memory, processing speed and language. CANTAB paired associates learning
      and spatial recognition tests identified the highest percentages of those in the
      'non-robust memory group. Processing speed partialled out the age effect on
      memory performance for the whole cohort, but the 'non-robust memory' group's
      performance was not associated with age or processing speed. CONCLUSIONS:
      Sensitive neuropsychological tests can detect performance below the norm in
      elderly people whose performance on MMSE and CAMCOG tests is well within the
      normal range. Age-related decline in memory performance in a cohort of the
      elderly may be largely due to inclusion within the cohort of individuals with
      undetected pre-clinical Alzheimer's disease or isolated memory impairment.

PMID- 11989994
TI  - Inter-episodic morbidity and drop-out under carbamazepine and lithium in the
      maintenance treatment of bipolar disorder.
AB  - BACKGROUND: Evaluation of mood-stabilizing treatment strategies usually focuses
      on their efficacy in preventing recurrences. The aim of this study is to
      supplement evaluation by two important aspects: inter-episodic morbidity and drop
      out. METHODS: Using a global outcome measure, response to prophylactic lithium
      and carbamazepine was evaluated in N = 171 bipolar patients (DSM-IV)
      participating in a randomized controlled trial with an observation period of 2
      1/2 years (MAP study). RESULTS: The rates of re-hospitalization were similar for
      both treatments. However, the percentage of good clinical response (i.e. patients
      with a low score of inter-episodic morbidity and without both re-hospitalization
      and drop-out during the observation period) was significantly higher in patients
      randomized to lithium (40% v. 24%). This superiority of lithium resulted
      essentially from a lower drop-out rate in patients without re-hospitalization
      (17% v. 42%). Regarding severity of inter-episodic morbidity, no clear difference
      between the drugs was found. For both medications the predominant symptomatology
      was minor depressive (but not manic, mixed or schizoaffective) symptoms. In the
      lithium group, inter-episodic morbidity in patients without re-hospitalization
      significantly decreased during the first 10 months and remained on the lower
      level for the rest of the observation period. For carbamazepine, reduction of
      inter-episodic morbidity over time did not reach statistical significance. Inter
      episodic morbidity was significantly related to drop-out and to re
      hospitalization for both medications. CONCLUSION: Taking inter-episodic
      morbidity, drop-out and re-hospitalization into consideration, the response rate
      in bipolar patients (DSM-IV) was higher for prophylactic lithium than for
      carbamazepine. The global outcome parameter used appears to be a valuable measure
      of clinical response to mood stabilizing drugs.

PMID- 11989995
TI  - Cognition following acute tryptophan depletion: difference between first-degree
      relatives of bipolar disorder patients and matched healthy control volunteers.
AB  - BACKGROUND: Serotonergic circuits have been proposed to mediate cognitive
      processes, particularly learning and memory. Cognitive impairment is often seen
      in bipolar disorders in relation to a possible lowered serotonergic turnover.
      METHODS: We investigated the effects of acute tryptophan depletion (ATD) on
      cognitive performance in healthy first-degree relatives of bipolar patients (FH)
      (N= 30) and matched controls (N= 15) in a placebo-controlled, double-blind cross
      over design. Performance on planning, memory and attention tasks were assessed at
      baseline and 5 h after ATD. RESULTS: Following ATD, speed of information
      processing on the planning task was impaired in the FH group but not in the
      control group. FH subjects with a bipolar disorder type I relative (FH I) showed
      impairments in planning and memory, independent of ATD. In all subjects, ATD
      impaired long-term memory performance and speed of information processing. ATD
      did not affect short-term memory and focused and divided attention. CONCLUSIONS:
      The results suggest serotonergic vulnerability affecting frontal lobe areas in FH
      subjects, indicated by impaired planning. Biological vulnerability in FH I
      subjects is reflected in impaired planning and memory performance. In conclusion,
      the cognitive dysfunctions in FH subjects indicate an endophenotype constituting
      a possible biological marker in bipolar psychopathology. Serotonin appears to be
      involved in speed of information processing, verbal and visual memory and
      learning processes.

PMID- 11989996
TI  - Functional effects of agents differentially selective to noradrenergic or
      serotonergic systems.
AB  - BACKGROUND: The diversity of pharmacological actions of antidepressants suggests
      that they may bring about their clinical effects by different functional means.
      METHODS: Twenty healthy volunteers were randomized in a cross-over design to
      receive 2 weeks of a clinical dose of both reboxetine and sertraline. Baseline
      assessments of personality were made using the Cloninger Tridimensional
      Personality Questionnaire and the Karolinska Scales of Personality. Daily and
      weekly ratings of mood (POMS and PANAS) and quality of life (SASS) were
      undertaken. RESULTS: Reboxetine and sertraline differed in their effects on the
      SASS as well as on measures of mood. Reboxetine appeared more likely to be energy
      enhancing; the effects of sertraline were more difficult to quantify. Personality
      factors, such as harm avoidance predicted the preference of subjects for these
      effects and the effect of being on a preferred drug had a significant impact on
      SASS, and ratings of moods as well as on self-assessments of personality.
      CONCLUSIONS: The differences reported here are consistent with the original
      thinking that led to the development of the SSRIs. The findings point to the need
      for further research on possible differential functional effects of psychotropic
      agents selective to different brain systems. The findings also have implications
      for clinical practice, in particular for maintenance treatment with
      antidepressants.

PMID- 11989997
TI  - The concordance of ICD-10 acute and transient psychosis and DSM-IV brief
      psychotic disorder.
AB  - BACKGROUND: ICD-10 acute and transient psychotic disorder (ATPD; F23) and DSM-IV
      brief psychotic disorder (BPD; 298.8) are related diagnostic concepts, but little
      is known regarding the concordance of the two definitions. METHOD: During a 5
      year period all in-patients with ATPD were identified; DSM-IV diagnoses were also
      determined. We systematically evaluated demographic and clinical features and
      carried out follow-up investigations at an average of 22 years after the index
      episode using standardized instruments. RESULTS: Forty-two (4.1%) of 1036
      patients treated for psychotic disorders or major affective episode fulfilled the
      ICD-10 criteria of ATPD. Of these, 61.9% also fulfilled the DSM-IV criteria of
      brief psychotic disorder; 31.0%, of schizophreniform disorder; 2.4%, of
      delusional disorder; and 4.8%. of psychotic disorder not otherwise specified. BPD
      showed significant concordance with the polymorphic subtype of ATPD, and DSM-IV
      schizophreniform disorder showed significant concordance with the
      schizophreniform subtype of ATPD. BPD patients had a significantly shorter
      duration of episode and more acute onset compared with those ATPD patients who
      did not meet the criteria of BPD (non-BPD). However, the BPD group and the non
      BPD group of ATPD were remarkably similar in terms of sociodemography (especially
      female preponderance), course and outcome, which was rather favourable for both
      groups. CONCLUSIONS: DSM-IV BPD is a psychotic disorder with broad concordance
      with ATPD as defined by ICD-10. However, the DSM-IV time criteria for BPD may be
      too narrow. The group of acute psychotic disorders with good prognosis extends
      beyond the borders of BPD and includes a subgroup of DSM-IV schizophreniform
      disorder.

PMID- 11989998
TI  - Do schizophrenic patients who managed to get to university have a non
      developmental form of illness?
AB  - BACKGROUND: Many people who develop schizophrenia have impairments in
      intellectual and social functioning that are detectable from early childhood.
      However, some patients do not exhibit such deficits, and this suggests that they
      may have suffered less neurodevelopmental damage. We hypothesized that the
      aetiology and form of schizophrenia may differ in such patients. We therefore
      studied a group of schizophrenic patients who were functioning well enough to
      enter university prior to illness onset. METHODS: The casenotes of 46 university
      educated patients and 48 non-university-educated patients were rated on several
      schedules including the OPCRIT checklist, and the two groups were compared using
      univariate statistical techniques. Principal components analysis was then
      performed using data from all patients, and the factor scores for each principal
      component were compared between groups. RESULTS: Univariate analyses showed the
      university-educated patients had an excess of depressive symptoms, and a paucity
      of core schizophrenic symptoms. Four principal components emerged in the
      principal components analysis: mania, biological depression, schizophrenic
      symptoms, and a reactive depression. University-educated patients scored
      significantly higher on the reactive depression principal component, and lower on
      the schizophrenic symptoms principal component, than the non-university-educated
      patients.

PMID- 11989999
TI  - Empty nest or revolving door? A prospective study of women's quality of life in
      midlife during the phase of children leaving and re-entering the home.
AB  - BACKGROUND: This study documents changes in household composition and effects on
      women's quality of life of children leaving and returning home. METHODS: A 9-year
      annual prospective study of a population-based sample of mid-aged Australian-born
      women who were premenopausal at baseline (N = 438) was conducted. Documentation
      was made of household composition and change, well-being, bothersome symptoms,
      daily hassles, feelings for partner and frequency of sexual activities. RESULTS:
      There was an increase in the number of women living alone, and a reduction in
      number of households in which there were children or parents. Each year > 25% of
      women reported a change in household composition. In the first year after the
      last child departed (N = 155), there was an improvement in women's positive mood
      and total well-being and a reduction in negative mood and the number of daily
      hassles. This improvement in mood was confined to those women who at baseline
      were not worried about children leaving home. In the first year after children
      return home there was a trend towards reduced frequency of sexual activities but
      no mood changes. CONCLUSIONS: For the majority of women, the departure of the
      last child from the household leads to positive changes in women's mood state and
      a reduced number of daily hassles. Return of offspring may have an adverse effect
      on sexual relating of the parents.

PMID- 11990000
TI  - Cannabis use in the last year in a US national sample of twin and sibling pairs.
AB  - BACKGROUND: Three prior population-based twin studies, none of which was
      nationally representative, suggested that both genetic and familial-environmental
      factors contribute to family resemblance for lifetime cannabis use. We seek to
      replicate these results in a US national probability sample of twin and sibling
      pairs examining only last year cannabis use. METHODS: Cannabis use in the last
      year was assessed by self-report questionnaire. Biometrical twin analyses were
      performed. RESULTS: Twin and sibling resemblance for last-year cannabis use was
      substantial, and much higher in monozygotic pairs than in dizygotic and sibling
      pairs, where levels of resemblance were similar. Modeling suggested that sibling
      resemblance was due to genetic factors--with a heritability of at least 60% and
      probably family environmental factors. No evidence was found that cannabis use
      was influenced by a special twin environment. CONCLUSIONS: Consistent with prior
      studies, use of cannabis is substantially influenced by genetic factors but
      family-environment is also possibly of importance.

PMID- 11990001
TI  - Duration of untreated psychosis (DUP) and outcome in schizophrenia.

PMID- 11990002
TI  - Nutritional and metabolic consequences of the early Maillard reaction of heat
      treated milk in the pig. Significance for man.
AB  - BACKGROUND: During the processing of foods, the Maillard reaction may occur
      contributing to altering the nutritional value of proteins. In dairy products the
      formation of lactuloselysine reduces the availability of lysine but the effects
      on the other nutrients are not very well known. AIM OF THE STUDY: Determination
      of the consequences of a high level of lactuloselysine in milk on the
      bioavailability of skim milk nutrients and the kinetics of their appearance in
      the portal blood and of their urinary and faecal excretions and extrapolation to
      lower heat treatments and to man, using the pig model. METHODS: Sub-adult pigs
      were fitted, under anaesthesia, with permanent catheters in the portal vein,
      carotid artery and urethra, and with an electromagnetic flow probe around the
      portal vein. Each animal was successively fed with two experimental meals
      containing an equal amount of dried skim milk (SM), either lyophilised or heat
      treated to obtain an intense Maillard reaction, (M-SM) resulting in a 50% lysine
      blockage. Portal and arterial concentrations and flux of individual amino acids
      (AA), glucose, galactose and fructoselysine were measured for a period of 12h
      after the meals. Lysine, fructoselysine and AA excreted in the urine and faeces
      within 72h were also determined. RESULTS: In M-SM containing 50% blocked lysine,
      no other AA was chemically modified. Fructoselysine appeared in the portal blood
      very late compared to amino acids resulting from a very slow release and
      corresponded to 8.2 and 18.6% of the ingested amount after 12 and 72h,
      respectively. Significant changes of the appearance in the portal blood were
      observed only for lysine (-60%), alanine (-17%) and cystine (+37%). A small
      decrease in the digestibility of most AA during the same period was observed,
      which was significant after 48h for lysine, phenylalanine, cystine, aspartic
      acid, glycine and total AA (-6%). CONCLUSION: It was confirmed that
      lactuloselysine was not bioavailable. The loss in protein nutritive value was
      mainly due and proportional to the deterioration of lysine and, to a lesser
      extent, to the decrease in the digestibility of some essential AA. Taking into
      account the very high level of lactuloselysine in the M-SM sample studied, it may
      be concluded that in common foods such as milk, infant formulas, biscuits, bread,
      pasta, containing lower levels of blocked lysine, the nutritional loss is
      primarily due to the loss of lysine and to a less extent to the decrease in the
      digestibility of other essential AA.

PMID- 11990003
TI  - Effects of long-term supplementation with whey proteins on plasma glutathione
      levels of HIV-infected patients.
AB  - BACKGROUND: HIV infection is characterized by an enhanced oxidant burden and a
      systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The
      semi-essential amino acid cysteine is the main source of the free sulfhydryl
      group of GSH and limits its synthesis. Whey proteins are rich in cysteine as well
      as in GSH precursor peptides. AIM OF THE STUDY: In order to evaluate the effects
      of whey supplementation on plasma GSH levels, HIV-infected patients were treated
      with whey proteins for a period of six months. METHODS: In a double blind
      clinical trial, 30 patients were randomized to a daily dose of 45 g whey proteins
      of either Protectamin (Fresenius Kabi, Germany) or Immunocal (Immunotec, Europe)
      for 2 weeks. Eighteen patients (16 male, 42 +/- 9.4 yr, 249 +/- 99 CD4+
      lymphocytes/l) continued the trial with a daily dose of 45 g of Protectamin for
      six months. RESULTS: Pre-therapy, total plasma GSH levels (Protectamin: 1.92 +/-
      0.6 microM; Immunocal: 1.99 +/- 0.9 microM) were less than normal (2.64 +/- 0.7
      microM, p = 0.03). After two weeks of whey protein supplementation, plasma total
      GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.1 microM,
      p = 0.004), while the difference in the Immunocal group did not reach
      significance (+24.5 +/- 59 %, 2.51 +/- 1.48 microM, p = 0.43). Consequently, all
      patients continuing the trial were openly switched to Protectamin. After six
      months, total GSH plasma levels were still significantly elevated compared to
      baseline (day 1: 1.95 +/- 0.8 microM vs. month 1: 2.18 +/- 0.8 microM, p = 0.19;
      month 3: 2.39 +/- 0.9 microM, p = 0.056; month 6: 2.47 +/- 0.8 microM, p =
      0.033). Body weight, T-cell counts, and other clinical parameters did not change.
      The most common mild side effect was intestinal disturbance; severe adverse
      events did not occur. CONCLUSION: Supplementation with whey proteins persistently
      increased plasma glutathione levels in patients with advanced HIV-infection. The
      treatment was well tolerated. A larger long-term trial is clearly warranted to
      evaluate whether this positive influence on the glutathione metabolism translates
      into a more favorable course of the disease.

PMID- 11990004
TI  - The hypocholesterolemic effect of lemon peels, lemon pectin, and the waste stream
      material of lemon peels in hybrid F1B hamsters.
AB  - BACKGROUND: We found in preliminary studies with hamsters that citrus peels have
      a cholesterol lowering effect comparable to that of pectin extracted from these
      peels. AIM OF THE STUDY: We wanted to examine whether the cholesterol lowering
      effect of the peels could be completely accounted for by the pectin in the peels.
      METHODS: We fed cholesterol enriched (0.1 %,w/w) semipurified diets containing 3%
      (w/w) of cellulose, lemon peels, lemon pectin, and the waste stream material of
      the lemon peels to hybrid F1B hamsters for a period of 8 weeks. The waste stream
      of the lemon peels is the left over after extraction of the lemon pectin.
      RESULTS: Feeding the semipurified diets resulted in an increase of plasma
      cholesterol levels in all the dietary groups after 2 and 4 weeks on the diets.
      Cholesterol concentrations in the cellulose fed hamsters continued to increase
      after 4 weeks on the diet, whereas cholesterol levels in the other groups had
      reached a plateau. As a consequence, the plasma cholesterol levels in the
      hamsters fed the peels (5.59 +/- 0.74 mmol/L, mean +/- SD, n = 14), pectin (5.19
      +/- 0.48 mmol/L), or waste stream (5.53 +/- 0.94 mmol/L) were lower than those in
      the hamsters fed cellulose (6.71 +/- 1.52 mmol/L) after 8 weeks on the diets.
      Differences in total plasma cholesterol were reflected in differences in both
      VLDL and LDL cholesterol concentration, but this effect was more distinct for the
      VLDL. There was no effect of the type of fiber on HDL cholesterol levels. Liver
      cholesterol concentrations paralleled. the concentrations of plasma cholesterol
      and the liver cholesterol concentrations in the hamsters fed the peels (3.57+/-
      1.01 micromol/g liver, mean +/- SD, n = 14), pectin (4.86 +/- 1.42), and the
      waste stream (4.96 +/- 1.89) were lower than those in the cellulose group (7.19
      +/- 2.32). The hamsters fed the peels, pectin, or waste stream tended to have a
      higher excretion of fecal bile acids and neutral sterols then the cellulose fed
      hamsters. CONCLUSION: The results of this study suggest that lemon peels and the
      waste stream of the lemon peels are as effective in lowering plasma and liver
      cholesterol in hamsters as the pectin extracted from the peels and that also
      compounds other than pectin are probably responsible for the cholesterol lowering
      effect of the citrus peels.

PMID- 11990005
TI  - Vitamin C and vitamin E antagonistically modulate human vascular endothelial and
      smooth muscle cell DNA synthesis and proliferation.
AB  - BACKGROUND: Vitamin C and E are suggested to play a preventive role in the
      pathogenesis of atherosclerosis. They reduce oxidation of low density
      lipoproteins (oxLDL), thereby protecting human vascular arterial endothelial and
      smooth muscle cells from oxLDL induced damages. AIMS OF THE STUDY: Since vascular
      arterial endothelial and smooth muscle cells are both involved in atherosclerotic
      plaque formation, we simultaneously examined the effect of vitamin C, E and oxLDL
      on their DNA synthesis and proliferation to further elucidate their joint role in
      this process. METHODS: Human umbilical arterial endothelial cells (HUAEC) and
      human arterial smooth muscle cells (HUASMC) were incubated with "preventive
      concentrations" of vitamin C (60 microM) and E (30 microM) and with LDL (60
      microg/ml) of increasing oxidation grade. Cell proliferation and DNA synthesis
      were determined by cell count and [3H]-thymidine uptake, respectively. RESULTS:
      Vitamin C alone or in combination with E increased significantly cell number and
      [3H]-thymidine uptake in HUAEC. The combination exhibited the strongest effect.
      In contrast, cell number and [3H]-thymidine uptake in HUASMC were significantly
      decreased in the presence of vitamin C, vitamin E or its combination. OxLDL (60
      microg/ml) inhibited cell number and [3H]-thymidine uptake in HUAECs, the latter
      in an oxidation-grade dependent manner. In HUASMC oxLDL promoted a higher cell
      number and [3H]-thymidine uptake. If induced by minimally oxLDL, this reduction
      or increase could be partially reversed by vitamin C alone or in combination with
      vitamin E. CONCLUSION: Vitamin C and E, alone or in combination, modulate
      proliferation and DNA synthesis of human arterial endothelial and muscle cells
      and this modulation is antagonistic. Thus, vitamin C and E may act "preventive"
      on atherosclerotic plaque formation in two steps: first reendothelialisation is
      promoted, then HUASMC growth is inhibited.

PMID- 11990006
TI  - Alcohol, cigarette smoking, dietary factors and the risk of colorectal adenomas
      and hyperplastic polyps--a case control study.
AB  - BACKGROUND & AIMS: Epidemiological studies on the association between lifestyle
      factors and the risk of colorectal polyps have led to conflicting results. The
      aim of the present study was to assess the relationship between alcohol
      consumption, dietary risk factors, cigarette smoking and colorectal adenomas or
      hyperplastic polyps, respectively. METHODS: In formation on alcohol consumption,
      a detailed dietary history, cigarette smoking and intake of non-steroidal anti
      inflammatory drugs was collected among 502 Caucasian subjects undergoing complete
      colonoscopy, 207 with colorectal adenomas, 71 with hyperplastic polyps and 224
      controls with no polyps. RESULTS: Using univariate analysis significant risk
      factors for adenomas were age above 55 years, male sex, BMI > 24 (OR 1.91 [1.26
      2.88]), an intake of ham + sausage > 15 g/day (OR 1.87 [1.12-3.11]) and smoking
      (OR 1.71 [1.17-2.5]). The association with alcohol intake > 7 g/day was not
      significant (OR 1.42 [0.97-2.07], p = 0.071). In the multiple logistic regression
      only age > 55 years (OR 2.97 [1.94-4.52]), male sex (OR 2.12 [1.54-3.6]) and
      smoking (OR 1.56 [1.01-2.39]) were significant risk factors for adenomas.
      Unexpectedly the mean consumption of alcohol, wine and beer, was significantly
      lower in subjects in whom adenomas were localized only in the rectum compared to
      those having adenomas in the sigmoid or in the proximal colon. Significant risk
      factors in subjects with hyperplastic polyps on univariate analysis were intake
      of > 15 g of ham and sausage/day (OR 3.70 [1.49-9.19]), smoking (OR 1.79 [1.04
      3.06]) and male sex. In the multiple logistic regression only intake of > 15
      g/day of ham + sausage and male sex were significant risk factors (OR 3.24 [1.23
      140.8] and 1.83 [1.05-318], respectively). CONCLUSION: When controlling for other
      potential risk factors, smoking was the only significant lifestyle risk factor
      for colorectal adenomas and the intake of ham and sausage > 15 g/day for
      hyperplastic polyps. The intake of alcohol, wine and beer were markedly higher in
      subjects with adenomas of the colon compared to those with adenomas in the
      rectum.

PMID- 11990007
TI  - Psychiatric disorders in Sardinian immigrants to Paris: a comparison with
      Parisians and Sardinians resident in Sardinia.
AB  - BACKGROUND: The aim of the present study was to compare the prevalence of ICD-10
      psychiatric disorders in a community sample of subjects of Sardinian origin
      resident in Paris (here "immigrants"), of the general Parisian population
      ("Parisians") and of Sardinians resident in Sardinia ("Sardinians"). METHODS: The
      sample of immigrants was obtained by contacting a fifth of all households with a
      Sardinian surname in Paris telephone directories. The other samples have already
      been partially described in previous studies. All subjects were interviewed using
      the CIDIS, a shortened version of the structured WHO interview CIDI. RESULTS:
      High or very high response rates were achieved in all studies. The final sample
      sizes were: 153 immigrants, 2,260 Parisians and 1,040 Sardinians. Immigrants
      showed high rates of depressive disorders, as did Parisians, and high rates of
      anxiety disorders, as did Sardinians. The immigrants' offspring (second
      generation immigrants) seemed to be particularly at risk for depression, drug
      abuse and bulimia. Elderly Sardinians who had returned to Sardinia after a long
      period of emigration showed an increased risk of dysthymia. The presence of a
      confidential relationship had a protective effect. CONCLUSIONS: The results are
      consistent with previous findings which suggest a greater risk of anxiety
      disorders in Southern Europe and of depression in Northern European countries.
      Immigrants in this study seem to present a particularly unfavourable pattern of
      mental disorders compared to both origin and host populations. The role of social
      support, use of mental health services and social conditions of second-generation
      immigrants should be analysed in greater depth.

PMID- 11990008
TI  - Prevalence and determinants of minor psychiatric disorder in Turkish immigrants
      living in The Netherlands.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of and risk and
      protective factors for minor psychiatric disorder in a general population sample
      of Turkish immigrants living in the Netherlands. METHODS: Minor psychiatric
      disorder was assessed with the 28-item version of the General Health
      Questionnaire. Demographic, immigration, social and support, and stress related
      variables were assessed with the Turkish Immigrant Assessment Questionnaire. The
      study sample was a randomly selected sample of 262 male and 523 female Turkish
      immigrants. RESULTS: Of all immigrants, 33.4% experience minor psychiatric
      disorder with more females (36.1%) than males (27.9%) with disorder. For males,
      unemployment is a strong risk factor, whereas for females the burden of
      additional tasks (physical illness and inclusion of family members) in the
      household increases the risk for psychiatric disorder. For both males and
      females, however, the quality of the relationship with their partner in addition
      to enduring stresses around housing and finances are associated with elevated
      risks. CONCLUSIONS: The incidence of minor psychiatric disorder in this sample of
      Turkish immigrants living in the Netherlands is higher than the incidence
      normally found in general population samples. The expression of somatic
      complaints around 'tightness' should alert physicians to further explore symptoms
      of minor psychiatric disorder and to examine sources of distress stemming from
      the partner relationship, the family, work and from poor housing and financial
      conditions.

PMID- 11990009
TI  - Postnatal depression in turkey: epidemiological and cultural aspects.
AB  - BACKGROUND: In some periods of a woman's life the risk of depression increases
      and the postnatal period is one of these. The prevalence and the risk factors of
      postnatal depression are not systematically studied in Turkey. The aim of this
      study is to investigate the epidemiological aspects and the cultural factors that
      may affect postnatal depression in our country. METHOD: According to the records
      of ten primary health care centres in Manisa, a city in western Turkey, there
      were 1,337 women who had given birth in the previous 6 months. A sample group of
      317 mothers were randomised among these women and 257 (81.7%) of the sample group
      could be reached. Data were collected by use of the Edinburgh Postnatal
      Depression Scale and a questionnaire on sociodemographic variables designed for
      this study. RESULTS: The mean depression score was found to be 7.54 +/- 4.66.
      When the cut-off point was taken into consideration, 14% of mothers had a
      syndromal depression. The factors which affected the prevalence of depression
      were the number of living children, living in a shanty, being an immigrant,
      serious health problems in the baby, previous psychiatric history, psychiatric
      disorder in the spouse, and having bad relations with the spouse and his parents.
      CONCLUSION: These findings revealed that the prevalence of postnatal depression
      in the Manisa province and the factors affecting it were very similar to other
      studies; but the negative impact of bad relations of the mother with her family
      in-law on postnatal depression seems to be a distinguishing aspect of Turkish
      culture.

PMID- 11990010
TI  - Religious delusions in patients admitted to hospital with schizophrenia.
AB  - BACKGROUND: Religious delusions are clinically important because they may be
      associated with selfharm and poorer outcomes from treatment. They have not been
      extensively researched. This study sought to investigate the prevalence of
      religious delusions in a sample of patients admitted to hospital with
      schizophrenia, to describe these delusions and to compare the characteristics of
      the patients with religious delusions with schizophrenia patients with all other
      types of delusion. METHOD: A cross-sectional investigation was carried out. The
      prevalence of religious delusions was assessed and comparisons were made between
      religiously deluded patients and a control group on demographic, symptom,
      functioning and religious variables. One hundred and ninety-three subjects were
      examined of whom 24% had religious delusions. RESULTS: Patients with religious
      delusions had higher symptom scores (as measured by the PANSS), they were
      functioning less well (as measured by the GAF) and they were prescribed more
      medication than those patients with schizophrenia who had other types of
      delusion. CONCLUSION: It is concluded that religious delusions are commonly found
      in schizophrenia and that by comparison with other patients who have
      schizophrenia, those patients with religious delusions appear to be more severely
      ill. This warrants further investigation.

PMID- 11990011
TI  - Different study criteria affect the prevalence of benzodiazepine use.
AB  - BACKGROUND: Different prevalences of benzodiazepine (BZ) use are described in the
      literature. The present study assessed the effects of employing various
      definitions of BZ use and various observation periods on the prevalence rate of
      BZ use in an open population aged 18-74 years. METHOD: In a literature review,
      prevalence studies were systematically compared. In a second stage, a descriptive
      cross-sectional multipractice study was analysed using 48,046 prescriptions of BZ
      in the past year given to a population of 80,315 patients at 31 general practices
      in the Nijmegen Health Area. From this database, prevalence rates were calculated
      applying different definitions of BZ use and different observation periods.
      RESULTS: In the literature, prevalence rates varied between 2.2 and 17.6%. There
      was wide variation in definitions of BZ use and observation period. In our
      prescription database, depending on the definitions of BZ use and observation
      period, prevalence rates ranged from 0.2% to 8.9%. The ratio of female:male (2:1)
      remained constant irrespective of the prevalence rate. Age distribution varied
      according to the duration of use: among long-term BZ users, approximately 80%
      were older than 45 years; among short-term BZ users, approximately 55% were older
      than 45 years. CONCLUSIONS: The wide variation in prevalence rates of BZ use
      reported in the literature can largely be explained by differences in definitions
      of BZ use and observation period. This affected the distribution of some BZ-use
      related variables such as age. For reliable comparisons of BZ use,
      standardisation of the definition of BZ use is required. A proposal for
      standardising methodology is presented.

PMID- 11990012
TI  - Determinants of occurrence and recovery from hallucinations in daily life.
AB  - BACKGROUND: Data related to the dynamics of hallucinatory experiences of patients
      suffering from schizophrenia are scarce. Detecting antecedent conditions and
      coping strategies may aid development of targeted psychological interventions.
      METHOD: We studied hallucinating and non-hallucinating patients suffering from
      schizophrenia spectrum disorder (n = 57), and non-schizophrenic severe mentally
      ill patients with depression (n = 37). Data were collected using the Experience
      Sampling Method (ESM) over a period of 1 week. Contingent on a randomly
      signalling beep, subjects filled in reports of ongoing hallucinations as well as
      thought, mood, current activity, social circumstances and places frequented.
      RESULTS: More subjects suffering from schizophrenia reported hallucinations, but
      for all hallucinating subjects the qualities of hallucination episodes were quite
      similar. More subjects reported visual hallucinations at least once. In contrast,
      the intensity of auditory hallucinations was higher. Anxiety was the most
      prominent emotion during hallucinations and reports of anxiety intensity exceeded
      baseline levels before the first report of auditory hallucinations. Context
      modified hallucination intensity over the course of an episode. Social withdrawal
      resulted in a decrease of hallucinatory intensity (AH > VH), while social
      engagement slightly raised intensity levels (VH > AH). Doing nothing (VH > AH)
      and work activities (AH > VH) led to decreases in intensity levels over time,
      while passive leisure activities (watching TV) resulted in increases in intensity
      levels of hallucinations (AH > VH). CONCLUSION: The results suggest that
      hallucinating experiences are subject to a host of contextual influences.
      Understanding variation offers useful insights for therapy.

PMID- 11990013
TI  - Determination of crude protein in animal feed, forage, grain, and oilseeds by
      using block digestion with a copper catalyst and steam distillation into boric
      acid: collaborative study.
AB  - A collaborative study was conducted to evaluate the repeatability and
      reproducibility of an extension of AOAC Official Method 991.20, Nitrogen (Crude)
      in Milk, to animal feed, forage (plant tissue), grain, and oilseed materials.
      Test portions are digested in an aluminum block at 420 degrees C in sulfuric acid
      with potassium sulfate and a copper catalyst. Digests are cooled and diluted, and
      concentrated sodium hydroxide is added to neutralize the acid and make the digest
      basic; the liberated ammonia is distilled by using steam distillation. The
      liberated ammonia is trapped in a weak boric acid solution and titrated with a
      stronger standardized acid, hydrochloric acid; colorimetric endpoint detection is
      used. Fourteen blind samples were sent to 13 collaborators in the United States,
      Denmark, Sweden, Germany, and the United Kingdom. Recoveries of nitrogen from
      lysine, tryptophan, and acetanilide were 86.8, 98.8, and 100.1%, respectively.
      The within-laboratory relative standard deviation (RSDr, repeatability) ranged
      from 0.40 to 2.38% for crude protein. The among-laboratories (including within-)
      relative standard deviation (RSD(R), reproducibility) ranged from 0.44 to 2.38%.
      It is recommended that the method be adopted First Action by AOAC INTERNATIONAL.
      A lower concentration (1% H3BO3) of trapping solution was compared with the
      concentration specified in the original protocol (4% H3BO3) and was found
      comparable for use in an automatic titration system in which titration begins
      automatically as soon as distillation starts. The Study Directors recommend that
      1% H3BO3 as an optional alternative to 4% boric acid trapping solution be allowed
      for automatic titrators that titrate throughout the distillation.

PMID- 11990014
TI  - Determination of water (moisture) and dry matter in animal feed, grain, and
      forage (plant tissue) by Karl Fischer titration: collaborative study.
AB  - A Karl Fischer method for determining water (dry matter) in animal feed and
      forages was collaboratively studied. Water was extracted from animal feed or
      forage material into methanol-formamide (1 + 1) directly in the Karl Fischer
      titration vessel by high-speed homogenization. The water was titrated at 50
      degrees C with one-component Karl Fischer reagent based on imidazole. Ten blind
      samples were sent to 9 collaborators in the United States, Canada, and Germany.
      The within-laboratory relative standard deviation (repeatability) ranged from
      1.14 to 6.99% for water or from 0.09 to 0.56% for dry matter. Among-laboratory
      (including within-) relative standard deviation (reproducibility) ranged from
      5.35 to 10.73%, or from 0.44 to 0.77% for dry matter. The authors recommend that
      the method be adopted as Official First Action by AOAC INTERNATIONAL. A
      comparable alternative extraction procedure using boiling methanol is also
      recommended for Official First Action.

PMID- 11990015
TI  - Automatic flow system titration based on multicommutation for spectrophotometric
      determination of total acidity in silage extracts.
AB  - A multicommutated flow titration procedure is proposed for the spectrophotometric
      determination of total acidity in silage extracts. The flow network comprises a
      set of 3-way solenoid valves, computer-controlled to provide facilities to handle
      the titrand, titrant, and carrier solutions by using a single pumping channel.
      The procedure is based on the volumetric fraction variation approach that
      maintains the same volume of titrand solution and varies the titrant solution
      step by step, to provide determination without the use of an analytical curve.
      The procedure is implemented by using phenolphthalein as an external indicator;
      the proposed algorithm was able to titrate silage extracts presenting different
      color intensities. Sample solutions with concentrations ranging from 10(-3) to
      10(-1) mol/L total acidity could be analyzed by using 10(-2) mol/L sodium
      hydroxide as the titrant solution. Other advantages include a relative standard
      deviation of <1.0% (n = 4) for a typical silage extract solution containing 26
      mmol/L total acidity; an analytical throughput of 16 determinations per hour was
      also achieved. Accuracy was assessed by processing a set of silage extract
      solutions and comparing the results with those obtained by using the conventional
      potentiometric titration procedure. No significant difference at the 95%
      confidence level was observed.

PMID- 11990016
TI  - Comparison between capillary electrophoresis and liquid chromatography for the
      determination of diclofenac sodium in a pharmaceutical tablet.
AB  - Two novel analytical methodologies using capillary electrophoresis (CE) and
      liquid chromatography (LC) were developed and compared for the determination of
      diclofenac sodium in commercial and simulated tablet formulations. The CE
      analysis was performed in a bare fused-silica capillary with 75 microm id and
      total length of 50 cm (28 cm to the detector) with a buffer solution of 20 mM
      sodium tetraborate, pH 9.23. The applied voltage was 20 kV, and acetaminophen was
      used as the internal standard (IS). The LC analysis was performed with a
      LiChrospher 100 RP-18 (5 microm) column and a mobile phase of methanol-diluted
      glacial acetic acid (0.3 parts in 2500; 75 + 25) at a flow rate of 0.9 mL/min
      with propylparaben as the IS. In both analyses, detection was by ultraviolet
      absorption at 276 nm. Under optimized conditions, the CE migration times for the
      diclofenac sodium standard and acetaminophen (IS) were 2.07 and 1.59 min,
      respectively, and the LC retention times for the diclofenac sodium standard and
      propylparaben (IS) were 3.98 and 2.26 min, respectively. The resolution and
      efficiency for CE were 14.2 and 1.6 x 10(5) plates/m, respectively, and for LC,
      5.0 and 8.6 x 10(3) plates/m, respectively. Calibration curves of peak area
      versus concentration gave correlation coefficients of 0.9992 for CE and 0.9994
      for LC. The limits of detection and quantitation were 8.40 and 25.46 microg/mL,
      respectively, for CE and 4.60 and 13.93 microg/mL, respectively, for LC.
      Coefficients of variation were 1.68 and 0.37% for CE and LC, respectively.
      Average recoveries obtained with CE and LC were 103.12+/-0.90 and 99.59+/-0.21%,
      respectively. Although both methodologies were shown to be suitable for the
      determination of diclofenac sodium in tablets, performing in a similar manner
      with regard to several aspects (linearity, recovery, and specificity), CE
      provided faster analysis and better column efficiency, whereas LC provided
      superior repeatability and sensitivity.

PMID- 11990017
TI  - Determination of oxytetracycline residues in matrixes from a freshwater
      recirculating aquaculture system.
AB  - This paper describes related procedures to determine the amount of
      oxytetracycline (OTC) present in trout tissue (muscle with skin attached),
      biofilter sand, sediment, and tank water from a recirculating aquaculture system.
      OTC was extracted from the matrixes by different techniques, depending on
      complexity of the matrix and desired OTC detection level in that matrix. Listed
      in order of increasing complexity, OTC was extracted from tank water by dilution
      with acidic buffer containing ethylenediaminetetraacetic acid (EDTA); from
      biofilter sand by shaking with 0.1 N HCl; from sediment by homogenization and
      shaking with buffer/EDTA; and from ground trout by homogenization and shaking
      with buffer/EDTA (twice), with further cleanup and concentration of the extract
      on a polymeric solid-phase extraction cartridge. The 4 procedures all used the
      same reversed-phase gradient chromatography on a polymeric column with UV
      detection at 350 nm. The lower limit of detection (estimated) and upper limit of
      validation for each of these 4 matrixes were 0.04-4.0 microg/g (ppm; trout), 0.03
      20 ppm (biofilter sand), 1-6000 ppm (sediment), and 0.003-10 ppm (water).
      Recoveries ranged from 82 to 108%, with relative standard deviation <20% over the
      applicable concentration ranges. These procedures were used to monitor OTC
      residues resulting from medicated feed administered to rainbow trout in a
      recirculating aquaculture system.

PMID- 11990018
TI  - Qualitative and quantitative reversed-phase liquid chromatography of a new
      bisisoxazolylnaphthoquinone.
AB  - The main objective of this study was to develop and test the applicability of a
      sensitive, accurate, and precise liquid chromatographic (LC) method for
      evaluating the stability characteristics of a new bisisoxazolylnaphthoquinone, 2
      (3,5-dimethyl-4-isoxazolylamino)-N-(3,5-dimethyl-4-isoxazolyl)-1,4-naphthoquinone
      4-imine compound 1. The method was shown to be selective and stability
      indicating. Isocratic elution with a mobile phase of methanol-water (75 + 25,
      v/v) on a reversed-phase column with UV detection at ambient temperature
      completely resolved compound 1 from its degradation products. The LC system was
      calibrated by plotting peak responses versus known concentrations of a reference
      standard by using an internal standardization procedure. Complete elution
      occurred after 12 min with a peak symmetry factor of 0.95 for the drug peak. The
      kinetic degradation of compound 1 was studied over a pH range of 0.88-14.00 to
      determine the kinetic parameters involved in its decomposition path in aqueous
      solution.

PMID- 11990019
TI  - Parallux beta-lactam: a capillary-based fluorescent immunoassay for the
      determination of penicillin-G, ampicillin, amoxicillin, cloxacillin, cephapirin,
      and ceftiofur in bovine milk.
AB  - An analytical system was developed for detection of antibiotic residues in bovine
      milk. The method is based on competitive fluorescent immunoassays in glass
      capillary tubes (U.S. Patent No. 5,624,850). The system consists of an assay
      cartridge containing 4 glass capillaries, a reagent tray with 4 wells of dried
      reagents, and a Parallux processor, which processes the assay, reads fluorescent
      output, and reports test results. Minimum sensitivity for detection of 6 beta
      lactam antibiotics in bovine milk was determined to be penicillin-G, 3.2 ppb;
      ampicillin, 2.9 ppb; amoxicillin, 3.6 ppb; cloxacillin, 7.4 ppb; cephapirin, 16.3
      ppb; and ceftiofur, 33.7 ppb. The assay system was also specific and sensitive
      for detection of incurred residues at U.S. Food and Drug Administration tolerance
      levels: penicillin-G, 5 ppb; ampicillin, 10 ppb; amoxicillin, 10 ppb;
      cloxacillin, 10 ppb; cephapirin, 20 ppb; and ceftiofur, 50 ppb. There was no
      interference in detection of minimum sensitivity levels of antibiotic by the
      presence of somatic cells at approximately 1 x 10(6) cells/mL. Milk containing 3
      x 10(6) cells/mL bacteria commonly found in mastitic milk also showed no
      interference when tolerance levels of antibiotic were present. There was no
      detectable interference on results by a wide variety of non-beta-lactam drugs.

PMID- 11990020
TI  - Validation of a simple liquid chromatographic method for determination and
      quantitation of residual ivermectin and doramectin in pig liver.
AB  - A rapid and quantitative method for the extraction, derivatization, and liquid
      chromatography with fluorescence detection of ivermectin (IVM) and doramectin
      (DOM) residues in porcine liver was developed and validated. IVM and DOM were
      extracted from the liver samples with acetonitrile, the supernatant was
      evaporated to dryness at 37 degrees C under nitrogen, and the residue was
      reconstituted in 1-methylimidazole solution. After 2 min at room temperature, IVM
      and DOM were converted to a fluorescent derivative and then separated on a
      Hypersil ODS column. The derivatives of IVM and DOM were detected and quantitated
      with high specificity by fluorescence (excitation: 365 nm, emission: 475 nm).
      Abamectin was used as an internal standard. The mean extraction efficiencies from
      fortified samples (15 ng/g) were 75% for IVM and 70% for DOM. The limit of
      detection was 0.8 ng/g for both IVM and DOM.

PMID- 11990021
TI  - Use of a continuous flow solid-phase spectroscopic sensor using two sensing
      zones: determination of thiamine and ascorbic acid.
AB  - A simple, rapid, inexpensive, and automated flow-through solid-phase
      spectroscopic sensing device is proposed for the sequential determination of 2
      vitamins: thiamine and ascorbic acid. The vitamins are concentrated on ion
      exchange gels, thiamine on Sephadex SP C-25, and ascorbic acid on Sephadex QAE A
      25; both solid supports are packed in 2 different flow cells. The absorbance is
      monitored directly on the solid phase with a double-beam spectrophotometer at 250
      nm, without derivatization or additional elution. With the use of 2 carrier/self
      eluting solutions (0.1 5M sodium acetate/acetic acid and 0.18M citric
      acid/K2HPO4) and a sample volume of 1000 microL, the sensor responds linearly in
      the range of 0.5-15 and 3-50 microg/mL with detection limits of 0.14 and 0.36
      microg/mL for thiamine and ascorbic acid, respectively. When the method was
      applied to synthetic samples and pharmaceutical preparations, precise and
      accurate values were obtained.

PMID- 11990022
TI  - Multiresidue determination of pesticides in drinking and related waters by solid
      phase extraction and liquid chromatography with ultraviolet detection:
      interlaboratory study.
AB  - As part of a project funded by the European Commission (EC) for the development
      and evaluation of multiresidue methods for analysis of drinking and related
      waters, 17 European laboratories evaluated a method using styrene-divinylbenzene
      copolymer solid-phase extraction followed by liquid chromatography with diode
      array detection. The main aim of the study was to evaluate whether the method
      meets the requirements of EC Drinking Water Directive 98/83 in terms of accuracy,
      precision, and detection limit for 21 pesticides according to the following
      requirements: limit of detection, < or =0.025 microg/L; accuracy expressed as
      recovery, between 75 and 125%; and precision expressed as repeatability relative
      standard deviation of the method, <12.5%, and as reproducibility relative
      standard deviation of the method, <25%. Analyses for unknown concentrations were
      performed with commercial bottled and tap waters. All laboratories were able to
      achieve detection limits of 0.01 microg/L for all pesticides except pirimicarb
      (0.02 microg/L). The criteria for repeatability were met for all compounds.
      Terbutryn in bottled water and carbendazim in tap water did not meet the criteria
      for reproducibility. In terms of accuracy, the method met the requirements for
      all pesticides in both matrixes, except for metamitron. However, several
      compounds (linuron, terbutryn, propazine, metobromuron, and isoproturon) showed
      recoveries slightly below 75%.

PMID- 11990023
TI  - Enhanced recovery of Salmonella from apple cider and apple juice with universal
      preenrichment broth.
AB  - A comparison was made of the relative efficiencies of Universal Preenrichment
      (UP) broth and lactose broth for the recovery of a variety of Salmonella serovars
      from pasteurized and unpasteurized apple cider and pasteurized apple juice. Bulk
      portions of juice were contaminated with single Salmonella serovars at high and
      low levels of 0.4 and 0.04 CFU/mL, respectively. The juice was aged for a minimum
      of 5 days at 2-5 degrees C. On the day analysis was initiated, each of 20 test
      portions (25 mL) of the contaminated juice was preenriched in UP broth and in
      lactose broth. The Bacteriological Analytical Manual Salmonella culture method
      was followed thereafter. For pasteurized apple cider, UP broth recovered
      significantly (p < 0.05) more Salmonella-positive test portions than did lactose
      broth (112 and 75, respectively). For unpasteurized apple cider, UP broth
      recovered significantly more Salmonella-positive test portions than did lactose
      broth (326 and 221, respectively). For pasteurized apple juice, UP broth
      recovered more Salmonella-positive test portions than did lactose broth (93 and
      81, respectively). However, this difference was not statistically significant.
      These results indicate that UP broth should replace lactose broth for the
      analysis of pasteurized and unpasteurized apple cider and pasteurized apple
      juice.

PMID- 11990024
TI  - Validation of the Hygicult E dipslides method in surface hygiene control: a
      Nordic collaborative study.
AB  - A collaborative study with Enterobacteriaceae was conducted to validate Hygicult
      E dipslides by comparison with violet red bile glucose agar (VRBGA) contact
      plates and swabbing, using stainless steel surfaces artificially contaminated
      with microbes at various levels. Twelve laboratories participated in the
      validation procedure. The total number of collaborative samples was 108. The
      microbial level in each sample was assessed in triplicate by using the 3 above
      mentioned methods. No Enterobacteriaceae were used at the low inoculation level.
      At the middle inoculation level, the percentages detached from the test surfaces
      were 16.6 with the Hygicult E method, 15.3 with the contact plate method, and
      14.6 with swabbing; at the high innoculation level, the percentages were 14.5,
      15.8, and 9.8, respectively. The percentage of acceptable results after the
      removal of outliers was 97.2. Repeatability relative standard deviations ranged
      from 33.4 to 44.9%; reproducibility relative standard deviations ranged from 45.2
      to 77.1%. The Hygicult E dipslide, VRBGA contact plate, and swabbing methods gave
      similar results at all 3 microbial levels tested: <1.0 colony-forming units
      (CFU)/cm2 at the low level, 1.2-1.3 CFU/cm2 at the middle level (theoretical
      yield 8.0 CFU/cm2), and 1.2-2.0 CFU/cm2 at the high level (theoretical yield 12.5
      CFU/cm2).

PMID- 11990025
TI  - Comparison of assurance gold salmonella EIA, BAX for screening/Salmonella, and
      GENE-TRAK Salmonella DLP rapid assays for detection of Salmonella in alfalfa
      sprouts and sprout irrigation water.
AB  - The Assurance Gold Salmonella EIA, BAX for Screening/Salmonella, and GENE-TRAK
      Salmonella DLP rapid assays were compared with official cultural methods
      described in the Bacteriological Analytical Manual (BAM) for analysis of alfalfa
      sprouts and sprout irrigation water for the presence of Salmonella. The lower
      limits of detection of 4 serovars of Salmonella cells (S. tennessee, S. muenchen,
      S. mbandanka, and S. cubana) in pure culture were determined as approximately
      log10 2, 5, and 6 for the BAX, GENE-TRAK, and Gold EIA, respectively. Despite its
      low detection limit, the BAX did not perform as well as the other assays in
      analyzing contaminated sprouts and sprout irrigation water. For 4 different lots
      of sprouts and sprout irrigation water samples inoculated with the 4 serovars at
      low [1-2 colony forming units (CFU/g)] and high (68-180 CFU/g) levels, the BAX
      detected Salmonella in 58/64 (90.6%) of the samples, compared with 64/64 (100%)
      by the GENE-TRAK, Gold EIA, and BAM methods. Assay performance was also compared
      for analysis of naturally contaminated sprouts and sprout irrigation water with 3
      lots of alfalfa sprouted seeds associated with different salmonellosis outbreaks.
      Positive assay results for the naturally contaminated samples were Gold EIA 41,
      GENE-TRAK 36, BAM 33, and BAX 13.

PMID- 11990026
TI  - Determination of total fumonisins in corn by competitive direct enzyme-linked
      immunosorbent assay: collaborative study.
AB  - Fumonisins-mycotoxins produced by some Fusarium species-have been shown to be the
      causative agent of diseases in horses and other domesticated animals as well as
      possible carcinogens in humans. A collaborative study was conducted to evaluate
      the effectiveness of a competitive direct enzyme-linked immunosorbent assay (CD
      ELISA) for the determination of total fumonisins (B1, B2, and B3) in corn. The
      test portion was extracted with methanol-water (7 + 3), filtered, diluted, and
      tested on the CD-ELISA. Naturally and artificially contaminated corn test
      portions were sent to 13 collaborators in the United States. Naturally
      contaminated field test portions were prepared at 3 different levels.
      Artificially contaminated test portions were spiked at 1.0, 3.0, and 5.0 mg/kg
      total fumonisins (B1, B2, and B3). Average recoveries of total fumonisins were
      120, 100, and 90%, respectively. The relative standard deviations for
      repeatability ranged from 13.3 to 23.3% and the relative standard deviations for
      reproducibility ranged from 15.8 to 30.3% across all levels tested. HORRAT
      values, calculated for each individual sample, ranged from 1.24 to 1.94. This
      method demonstrated acceptable intra- and interlaboratory precision at the levels
      tested.

PMID- 11990027
TI  - Comparison of two post-column derivatization systems, ultraviolet irradiation and
      electrochemical determination, for the liquid chromatographic determination of
      aflatoxins in food.
AB  - This study compared 2 post-column derivatization (PCD) techniques for the
      determination of aflatoxins B1, B2, G1, and G2 (AFB1, AFB2, AFG1, and AFG2) by
      fluorescence detection after liquid chromatographic separation: ultraviolet (UV)
      irradiation (PCD(UV)) and electrochemical bromination (PCD(EC)). Photochemical
      fluorescence enhancement was obtained with 2 different commercially available
      systems (PCD(UV1) and PCD(UV2)). An electrochemical bromination apparatus was
      used for bromination. Analyses of naturally contaminated or spiked samples of
      corn, pistachio paste, peanut butter, fig paste, and animal feed showed that
      neither of the techniques resulted in derivatization-specific matrix
      interferences for any of the matrixes under study, even when extracts were not
      completely purified. The response ratios PCD(UV)/PCD(EC) for AFB1, AFB2, AFG1,
      and AFG2 were 0.86, 0.96, 0.70, and 0.96, respectively, for PCD(UV1) and 0.82,
      0.95, 0.60, and 0.90, respectively, for PCD(UV2). The long-term use of the UV
      lamps (300 h for PCD(UV1) and 343 h for PCD(UV2)) in the photochemical detectors
      showed that these ratios remained stable throughout the time frame investigated.
      The relative standard deviation obtained for each of the devices during the in
      house validation study ranged from 0.3 to 1.8% for PCD(UV1), from 0.8 to 1.3% for
      PCD(UV2), and from 0.9 to 2.0% for PCD(EC).

PMID- 11990028
TI  - Determination of trans-galactooligosaccharides in selected food products by ion
      exchange chromatography: collaborative study.
AB  - Eleven collaborating laboratories assayed 7 blind duplicate pairs of food and
      feed products for tans-galactooligosaccharides. The 7 laboratory sample pairs
      ranged from low (2%) to high levels (15%). Following the proposed method, the
      test samples were treated with beta-galactosidase and the released galactose was
      determined by ion-exchange chromatography. Repeatability standard deviation
      ranged from 2.9 to 11.6%; reproducibility standard deviation ranged from 4.6 to
      11.6%.

PMID- 11990029
TI  - Determination of vitamins A (retinol) and E (alpha-tocopherol) in foods by liquid
      chromatography: collaborative study.
AB  - A collaborative study was conducted for the determination of vitamins A and E.
      Existing AOAC liquid chromatographic (LC) methods are suited for specific
      vitamins A and E analytical applications. This method differs from existing
      methods in that it can be used to assay samples in all 9 sectors of the food
      matrix. Standards and test samples are saponified in basic ethanol-water
      solution, neutralized, and diluted, converting fats to fatty acids and retinol
      esters and tocopherol esters to retinol and tocopherol, respectively. Retinol and
      alpha-tocopherol are quantitated on separate LC systems, using UV detection at
      313 or 328 nm for retinol, and fluorescence detection (excitation 290 nm,
      emission 330 nm) for alpha-tocopherol. Vitamin concentrations are calculated by
      comparison of the peak heights or peak areas of vitamins in test samples with
      those of standards.

PMID- 11990030
TI  - Determination of total dietary fiber in selected foods containing resistant
      maltodextrin by enzymatic-gravimetric method and liquid chromatography:
      collaborative study.
AB  - A method was developed for determination of total dietary fiber (TDF) in foods
      containing resistant maltodextrin (RMD) which includes nondigestible
      carbohydrates that are not fully recovered as dietary fiber by conventional TDF
      methods such as AOAC 985.29 or 991.43. Because the average molecular weight (MW)
      of RMD is 2000 daltons, lower MW soluble dietary fiber components do not
      precipitate in 78% ethanol; therefore, RMD is not completely quantitated as
      dietary fiber by current AOAC methods. The accuracy and precision of the method
      was evaluated through an AOAC collaborative study. Ten laboratories participated
      and assayed 12 test portions (6 blind duplicates) containing RMD. The 6 test
      pairs ranged from 1.5 to 100% RMD. The method consisted of the following steps:
      (1) The insoluble dietary fiber (IDF) and high MW soluble dietary fiber (HMWSDF)
      were determined by AOAC 985.29. (2) Ion exchange resins were used to remove salts
      and proteins contained in the AOAC 985.29 filtrates (including ethanol and
      acetone). (3) The amount of low MWRMD (LMWRMD) in the filtrates were determined
      by liquid chromatography. (4) The TDF was calculated by summation of the IDF,
      HMWSDF, and LMWRMD fractions having nondigestible carbohydrates with a degree of
      polymerization of 3 and higher. Repeatability standard deviations (RSDr) were
      1.33-7.46%, calculated by including outliers, and 1.33-6.10%, calculated by not
      including outliers. Reproducibility standard deviations (RSDR) were 2.48-9.39%,
      calculated by including outliers, and 1.79-9.39%, calculated by not including
      outliers. This method is recommended for adoption as Official First Action.

PMID- 11990031
TI  - Determination of the total nitrogen content of hard, semihard, and processed
      cheese by the Kjeldahl method: collaborative study.
AB  - The objective of this collaborative study was to determine interlaboratory
      performance statistics for a modified and optimized version of AOAC Method
      920.123 for the determination of the total nitrogen content of hard, semihard,
      and processed cheese by Kjeldahl analysis. Details included addressing the issues
      of material homogeneity, test portion size (1 g), quantitative transfer (weighing
      on to filter paper), ensuring system suitability (nitrogen recoveries), and using
      AOAC Method 991.20 as the basis for nitrogen analysis. Fifteen laboratories
      tested 18 pairs of blind duplicate cheese materials with a crude protein content
      between 18 and 36%. Materials represented hard, semihard, and processed
      commercial cheeses with a wide range of composition. Statistical performance
      parameters expressed as crude protein (nitrogen x 6.38), g/100 g, with invalid
      and outlier data removed were mean = 26.461, repeatability standard deviation
      (Sr) 0.111, reproducibility standard deviation (S(R)) = 0.153, repeatability
      relative standard deviation (RSDr) = 0.42%, reproducibility relative standard
      deviation (RSDR) = 0.58%, repeatability (r) = 0.312, and reproducibility (R) =
      0.428. The interlaboratory study results were acceptable and comparable to those
      for the milk Kjeldahl nitrogen method on a relative nitrogen basis. The Study
      Directors recommend that this modified method for the determination of total
      nitrogen in hard, semihard, and processed cheese by Kjeldahl analysis be adopted
      First Action as an improved method to replace Method 920.123.

PMID- 11990032
TI  - Determination of nitrite in foods by single-sweep polarography.
AB  - In an acid medium, nitrite diazotized with p-rosaniline and then coupled with 8
      hydroxyquinoline in a weak alkaline medium produces azo compounds. The azo
      compounds produce a very sensitive polarographic wave at -0.70 V (versus the
      saturated calomel electrode). The height of the peak is linear with the
      concentration of nitrite in the range of 5 x 10(-9) to 5 x 10(-7) g/mL. The
      detection limit is 3 x 10(-9) g/mL. The electrochemical characteristics of the
      polarographic wave are also discussed. The method was used to determine nitrite
      in sausage. The results agree well with those obtained by spectrophotometry.

PMID- 11990033
TI  - Method extension study to validate applicability of AOAC Official Method 996.14
      Assurance polyclonal enzyme immunoassay for detection of Listeria monocytogenes
      and related Listeria spp. from environmental surfaces: collaborative study.
AB  - Test portions from 3 environmental surface types, representative of typical
      surfaces found in a food production facility, were analyzed by the Assurance
      Listeria Polyclonal Enzyme Immunoassay (EIA) and the U.S. Department of
      Agriculture/Food Safety and Inspection Service (USDA/FSIS) culture method for
      Listeria monocytogenes and related Listeria species. In all cases, naturally
      contaminated environmental test samples were collected from an actual food
      production facility by sponge or swab. Test samples from concrete surfaces were
      collected by both swab and sponge; sponge test samples were collected from rubber
      surfaces, and swabs were used to sample steel surfaces. Test portions from each
      surface type were simultaneously analyzed by both methods. A total of 23
      collaborators, representing government agencies, as well as private industry in
      both the United States and Canada, participated in the study. During this study,
      a total of 550 test portions and controls was analyzed and confirmed, of which
      207 were positive and 336 were negative by both methods. Six test portions were
      positive by culture, but negative by the EIA. Three test portions were negative
      by culture, but positive by the EIA. Two test portions were negative by EIA and
      by culture, but confirmed positive when EIA enrichment broths were subcultured to
      selective agars. The data reported here indicate that the Assurance Listeria EIA
      method and the USDA/FSIS culture method are statistically equivalent for
      detection of L. monocytogenes and related Listeria species from environmental
      surfaces taken by sponges or swabs.

PMID- 11990034
TI  - Method extension study to validate applicability of AOAC Official Method 997.03
      visual immunoprecipitate assay (VIP) for Listeria monocytogenes and related
      Listeria spp. from environmental surfaces: collaborative study.
AB  - Test portions from 3 environmental surface types, representative of typical
      surfaces found in a food production facility, were analyzed by the Visual
      Immunoprecipitate assay (VIP) and the U.S. Department of Agriculture/Food Safety
      and Inspection Service (USDA/FSIS) culture method for Listeria monocytogenes and
      related Listeria species. In all cases, naturally contaminated environmental test
      samples were collected from an actual food production facility by sponge or swab.
      Test samples from concrete surfaces were collected by both swab and sponge;
      sponge test samples were collected from rubber surfaces, and swabs were used to
      sample steel surfaces. Test portions from each surface type were simultaneously
      analyzed by both methods. A total of 27 laboratories, representing government
      agencies as well as private industry in both the United States and Canada,
      participated in the study. During this study, a total of 615 test portions and
      controls was analyzed and confirmed, of which 227 were positive and 378 were
      negative by both methods. Nine test portions were positive by culture, but
      negative by the VIP. Five test portions were negative by culture, but positive by
      the VIP. Four test portions were negative by VIP and by culture, but confirmed
      positive when VIP enrichment broths were subcultured to selective agars. The data
      reported here indicate that the VIP method and the USDA/FSIS culture method are
      statistically equivalent for detection of L. monocytogenes and related Listeria
      species from environmental surfaces taken by sponges or swabs.

PMID- 11990035
TI  - Testing antimicrobials against biofilm bacteria.
AB  - Standard laboratory methods are needed to assess the efficacy of antimicrobial
      agents that are applied to biofilm bacteria. Existing standard suspension tests
      and dried surface tests show much greater efficacy than antimicrobial agents
      applied to biofilms. The greater resistance of biofilm bacteria to antimicrobial
      agents can be attributed to a number of interacting factors, including reaction
      and diffusion processes that limit an agent's accessibility to bacteria,
      phenotypic changes in biofilm bacteria caused by stress, and adaptation of the
      bacteria. Because biofilm systems are so diverse, a variety of new biofilm tests
      with features that differ in important ways from existing tests will ultimately
      be required. For example, the biofilm test apparatus may include a pump and a
      continuous-flow stirred tank reactor. This report provides an overview of biofilm
      testing and suggests a strategy for creating standard test methods.

PMID- 11990036
TI  - Factors affecting multiresidue determination of priority herbicides when using
      solid-phase microextraction.
AB  - A solid-phase microextraction (SPME) procedure was developed for the
      determination of 10 selected organonitrogen herbicides (s-ethyl
      dibropylthiocarbamate [EPTC], molinate, propachlor, trifluralin, simazine,
      atrazine, propazine, terbuthylazine, alachlor, and prometryn) and was tested with
      various natural waters. Gas chromatography coupled with flame thermionic and mass
      spectrometric detection was used for quantitation. For this purpose,
      polydimethylsiloxane and polyacrylate fibers were used and the factors affecting
      the SPME process such as pH, ionic strength, methanol content, memory effect,
      stirring rate, and adsorption-time profile were investigated and optimized. By
      using spiked liquid chromatography water, optimal factors were determined to be
      25% salt, <0.5% methanol, stirring rate of 960 rpm, pH 4, and an equilibrium time
      of 30 min. These conditions were used in further studies of the fibers and in
      analysis of natural water samples. The method was applied to spiked natural
      waters such as ground water, sea water, lake water, and river water at a
      concentration range of 0.5-10 microg/L. Limits of detection ranged from 5 to 90
      ng/L, and precision ranged from 5 to 15% (as relative standard deviation),
      depending on the pesticide, fiber, and detector used. The recoveries of
      herbicides were 70.2-118.4%, and the average r2 values of the calibration curves
      were >0.99 for all analytes. The results demonstrate the suitability of the SPME
      method to determine these organonitrogen herbicides in various natural waters.
      River water samples originating from the Epirus region (Northwestern Greece) were
      analyzed to verify the performance of the optimized method by comparing the
      results obtained by SPME with those obtained by using conventional solid-phase
      extraction of the selected herbicides.

PMID- 11990037
TI  - Detection and isolation of Listeria monocytogenes from food samples: implications
      of sublethal injury.
AB  - Detection of L. monocytogenes is often limited by the performance of the
      enrichment media used to support bacterial growth to detectable levels. Because
      Listeria may exist at extremely low levels in foods, sample enrichment protocols
      must amplify these low initial populations to detectable limits. Listeria may
      also exist in an injured state in food products as a result of processing
      treatments such as heating, freezing, exposure to acids, or exposure to
      sanitizing compounds. Selective agents in enrichment media normally used for
      recovery of Listeria may inhibit repair and detection of sublethally injured
      Listeria, which may go on to repair, grow, and regain pathogenicity. Simple
      modifications to existing regulatory protocols, such as those that use more than
      one enrichment broth, raise sensitivity of detection to 90%. This review shows
      the efficacy of repair/enrichment strategies, which increase sensitivity of
      detection to 97.5-98.8% compared with 65-70% by standard regulatory protocols.
      Ribotype analysis of isolates obtained from meat samples reveals a complex
      microbial ecology, with striking differences in both number and distribution of
      distinct genetic types of Listeria, depending upon whether samples are enriched
      in selective or repair/enrichment media. In studies on enrichment of dairy
      environmental samples in University of Vermont medium and Listeria repair broth
      (UVM and LRB), combining these 2 primary enrichment media into a single tube of
      Fraser broth for dual secondary enrichment yielded a significantly higher
      percentage (p < 0.05) of Listeria-positive samples than did use of either LRB or
      UVM alone. Refinement of conventional Listeria recovery methods should consider
      the importance of the enrichment step, the nutritional needs of specific genetic
      types, and the physiological condition of Listeria isolates in foods.

PMID- 11990038
TI  - Optimized, one-step, recovery-enrichment broth for enhanced detection of Listeria
      monocytogenes in pasteurized milk and hot dogs.
AB  - A one-step, recovery-enrichment broth, optimized Penn State University (oPSU)
      broth, was developed to consistently detect low levels of injured and uninjured
      Listeria monocytogenes cells in ready-to-eat foods. The oPSU broth contains
      special selective agents that inhibit growth of background flora without
      inhibiting recovery of injured Listeria cells. After recovery in the anaerobic
      section of oPSU broth, Listeria cells migrated to the surface, forming a black
      zone. This migration separated viable from nonviable cells and the food matrix,
      thereby reducing inhibitors that prevent detection by molecular methods. The high
      Listeria-to-background ratio in the black zone resulted in consistent detection
      of low levels of L. monocytogenes in pasteurized foods by both cultural and
      molecular methods, and greatly reduced both false-negative and false-positive
      results. oPSU broth does not require transfer to a secondary enrichment broth,
      making it less laborious and less subject to external contamination than 2-step
      enrichment protocols. Addition of 150mM D-serine prevented germination of
      Bacillus spores, but not the growth of vegetative cells. Replacement of D-serine
      with 12 mg/L acriflavin inhibited growth of vegetative cells of Bacillus spp.
      without inhibiting recovery of injured Listeria cells. oPSU broth may allow
      consistent detection of low levels of injured and uninjured cells of L.
      monocytogenes in pasteurized foods containing various background microflora.

PMID- 11990039
TI  - Polymerase chain reaction-based methods for detection of Listeria monocytogenes:
      toward real-time screening for food and environmental samples.
AB  - A review is presented of nucleic acid amplification-based methodology,
      specifically polymerase chain reaction (PCR)-based assays, for the detection of
      Listeria monocytogenes in food and environmental samples. Until recently,
      developmental challenges including poor sensitivity, due in part to reaction
      inhibition by components of the sample matrix, and the potential for false
      positive reactions have limited routine application of PCR-based screening
      assays. Commercial assays address these challenges while offering convenient,
      standardized protocols, a high level of automation, and results within 2 days
      after the sampling date. Although sample enrichment is necessary to achieve
      desired detection limits, continued efforts toward template purification will
      facilitate the development of assays offering real-time, quantitative results.
      The development of ribonucleic acid (RNA) amplification-based assays may increase
      in importance, particularly if end-product testing is prioritized by regulatory
      agencies, as messenger RNA appears to serve as an accurate indicator of cell
      viability. Further, the increase in target copy number may improve assay
      sensitivity. PCR-based screening methods offer efficient, reliable results and
      are ideal for monitoring the presence of L. monocytogenes in foods and in the
      food processing environment.

PMID- 11990040
TI  - Virulence testing of Listeria monocytogenes.
AB  - A major problem in understanding foodborne listeriosis from both the basic
      science and regulatory perspectives revolves around the role played by virulence
      factors of Listeria monocytogenes and how these interact with host susceptibility
      to result in the observed incidence of disease. From a mechanistic perspective,
      this problem has been well investigated, and many virulence components of L.
      monocytogenes have been discovered. Deletion of these genes results in large
      reductions in virulence functions in vitro and in vivo. The clonal bacteria and
      genetically identical hosts necessary to solve the riddles associated with
      virulence mechanisms are not likely to reflect the natural diversity found among
      wild populations of L. monocytogenes, including those associated with food. These
      factors contribute to a major dilemma in risk assessment and risk management of
      foodborne listeriosis: Although low-level L. monocytogenes contamination of
      certain foods is relatively common, suggesting widespread exposure, illness is
      overwhelmingly associated with only a relatively small subpopulation (3 of the 13
      L. monocytogenes serotypes) and occurs in only a small proportion of susceptible
      individuals. Virulence testing based on DNA probes for virulence genes is
      confounded by the widespread distribution of these genes in food isolates. In
      terms of the distribution of virulence factors among food isolates of L.
      monocytogenes, only listeriolysin is well characterized, because beta-hemolysis
      is often used to confirm the presence of L. monocytogenes in foods. The presence
      of other virulence genes such as those involved in host cell invasion and cell-to
      cell spread (inlA and actA) among food isolates has not been extensively
      investigated. How the presence of these components translates into functional
      virulence as measured in vivo and in vitro is also unknown. Animal studies and
      cell culture systems show a range of virulence among food isolates of L.
      monocytogenes. However, clinical isolates included in such studies are not
      consistently more virulent than food isolates with no known human disease
      association. Where multiple serotypes or ribotypes are compared, it has been
      difficult to demonstrate a consistent pattern of increased virulence associated
      with any subtype(s) in animal or in vitro studies. Development of model systems
      that adequately reflect the complexity of the host-pathogen relationship remains
      a challenge.

PMID- 11990041
TI  - Molecular subtyping methods for Listeria monocytogenes.
AB  - Conventional, phenotypic, and DNA-based subtyping methods allow differentiation
      of Listeria monocytogenes beyond the species and subspecies level. Bacterial
      subtyping methods not only improve our ability to detect and track human
      listeriosis outbreaks, but also provide tools to track sources of L.
      monocytogenes contamination throughout the food system. The use of subtyping
      methods also provides an opportunity to better understand the population
      genetics, epidemiology, and ecology of L. monocytogenes. The last 5 years have
      seen tremendous advancements in the development of sensitive, rapid, automated,
      and increasingly easy-to-use molecular subtyping methods for L. monocytogenes.
      This review highlights key aspects of different L. monocytogenes subtyping
      methods and provides examples of their application in public health, food safety,
      population genetics, and epidemiology. A significant focus is on the application
      of subtyping methods to define L. monocytogenes subtypes and clonal groups, which
      may differ in phenotypic characteristics and pathogenic potential.

PMID- 11990042
TI  - The application of fiber core posts in restoring badly destroyed primary
      incisors.
AB  - Early childhood caries (ECC) represents a challenge to pediatric dentists
      especially, when teeth are badly destroyed. ECC involves the upper anterior teeth
      early in life and by the time the dentist sees the child, most of the coronal
      structure is lost. Dentally, this is a very devastating situation for both the
      dentist and parents, as in many cases, extraction of these teeth is the only
      option. With the introduction of new adhesive systems and restorative materials,
      a new approach for treating these teeth is explained and documented by clinical
      cases, where fiber core posts are introduced into the root canals of primary
      incisors for a distance of 2 to 3 mm. It is retained in place by flowable
      composite, then the coronal part is reconstructed by a strip crown to restore the
      crown form. After a follow up period of one year, only 2 teeth out of 30 had to
      be extracted. The failure was attributed to failure in pulpal therapy rather than
      failure in the restorations, which were totally intact. A laboratory testing of
      the fracture load resistance of the restored teeth proved that this technique
      significantly improved the fracture load resistance of composite celluloid
      crowns, making it a valuable procedure to consider when the coronal tooth
      structure is not enough to support and retain a composite celluloid strip crown.

PMID- 11990043
TI  - A new classification for crown fractures of teeth.
AB  - The aim of this work is to define a classification for traumatic injuries to
      crowns of teeth that offers a simplified interpretation, which can be
      communicated easily. These data will help us to evaluate the future restorations
      (composite resins, crowns, porcelain veneers) according to the variable design
      and extension of initial crown fracture lines. For this reason we conducted
      research on a vast sample of subjects, who presented different traumatic lesions,
      in order to obtain a specific selection of these typologies of injuries. We
      reviewed the literature for a complete, brief classification of simple use, which
      could serve our cause. The traditional classifications (Andreasen, Ellis, OMS)
      did not satisfy us for different reasons. In fact, they only consider the initial
      lesion situation, never focusing on the shape of the lesion and therefore never
      giving suggestions for the best kind of material for restoration. On the
      contrary, our interest is to define the kind of more valid materials according to
      the variable design of crown fracture lines, to foresee the duration of these
      materials and the best time to substitute them. To simplify and make our research
      a more affordable one, we created a 4 classes classification (A-B-C-D) and 3
      subclasses (b1-c1-d1). Class A: all the simple enamel lesions which involve a
      mesial or distal crown angle, or only the incisal edge; Class B: all the enamel
      dentin lesions, which involve a mesial or distal crown angle and the incisal
      edge. When a pulpal exposure exists we define it a Subclass b1; Class C: all the
      enamel-dentin lesions, which involve the incisal edge and at least a third of the
      crown surface. When a pulp exposure exists we define it a Subclass c1. Class D:
      all the enamel-dentin lesions, which involve a mesial or distal crown angle and
      the incisal or palatal surface, with root cement involvement (crown-root
      fractures). When a pulpal exposure exists we define it a Subclass d1. This
      classification showed how different kinds of lesions (Class B, b1, C and c1, in
      our new classification) fall under the same definition (enamel-dentinal
      fractures) in traditional classifications (Andreasen, Ellis). However, they need
      a wholly different clinical approach, and the material involved in the treatment
      shows different behavior and duration. This new classification simplified the
      gathering of data and the communication among practitioners, thus confirming its
      importance in getting optimal diagnostic and therapeutic protocols. It also
      allowed us to identify the most frequent crown fractures (Class B, b1 and C, c1)
      that in our sample of patients (age range: 8-18) are typically treated with
      composite resins or original fragment reattachment technique. All these studies
      brought us to develop this new "easy to use" classification of dental crown
      lesions that helped us to gather data easily, to choose the right materials to
      improve the communication among practitioners including by electronic means,

PMID- 11990044
TI  - Multidisciplinary evaluation and clinical management of mesiodens.
AB  - Supernumerary teeth are a disorder of odontogenesis relatively common in the oral
      cavity and characterized by an excess number of teeth. The term mesiodens is used
      to refer to an unerupted supernumerary tooth in the central region of the
      premaxilla between the two central incisors. The complications associated with
      mesiodens include: lack of eruption of permanent teeth, the deviation of the
      eruption path, rotations, retention, root re-absorption and pulp necrosis with
      loss of vitality, and diastema. Early detection of mesiodens is most important if
      such complications are to be avoided. This report describes the treatment of a
      maxillary central incisor impacted by a mesiodens. The case initially required
      only surgical treatment, to remove the supernumerary tooth. Successively,
      orthodontic therapy was done to bring into position the left permanent central
      incisor, which erupted physiologically, but rotated 90 degrees around along its
      long axis.

PMID- 11990045
TI  - Submerged teeth.
AB  - Submersion occurs when a previously erupted tooth becomes embedded in the oral
      tissues. The purpose of this paper is to examine the distribution, the degree of
      re-impaction, the rate of congenital absence of the successor buds and the
      treatment in 28 submerged teeth in 17 patients.

PMID- 11990046
TI  - Treatment of condylar fractures in children and youths: the clinical value of the
      occlusal plane orientation and correlation with facial development (case
      reports).
AB  - The relative position of the plane of occlusion to the cranial base determines
      the direction of the forces generated in the cranium during occlusal function.
      When the plane of occlusion is level and when the neuromuscular system is in
      harmony, the vectors of forces created by the closing muscles are directed to the
      central area of the cranium in a symmetrically balanced way. Unfortunately, TMJ
      fractures may alter completely this balance with loss of the support to the
      mandible against the temporal component and loss of the functional effect of the
      lateral pterygoid muscle on the mandible. Changes in orientation of the occlusal
      plane may result in facial alteration and asymmetries. In our experience, the
      restoration of a plan of occlusion orthogonally aligned to the forces of
      occlusion for a correct transfer of forces through the maxilla to the rest of the
      cranial bones is essential to allow proper face development. Two, quite similar
      cases of unilateral, dislocated condylar fracture treated in a different way,
      will be reported to demonstrate how this can occur. Available clinical data will
      be illustrated.

PMID- 11990047
TI  - Retention of composite resin restorations in class IV preparations.
AB  - Clinicians often utilized composite resin restorations in combination with
      different types of preparation to restore class IV fractures on anterior
      incisors. A new preparation technique called (stair-step chamfer technique) is
      investigated in this study to detect bond strength to tooth structure. Eighty
      eight bovine teeth were divided into 4 groups. Group I had twenty-three samples
      with a 45 degree bevel that extended 2 millimeters beyond the fracture line.
      Group II had twenty-three samples with a circumferential chamfer, which extended
      2 mm beyond the fracture line and half the enamel thickness in depth. Group III
      had twenty-three samples with a facial stair-step chamfer, which followed the
      anatomical contour and extended 2 mm beyond the fracture line with a lingual
      plain chamfer. Group IV had eighteen samples as controls, which were untreated
      teeth. The first three groups were prepared and restored with hybrid composite
      resin in conjunction with a single step bonding agent and as surface penetrating
      sealer, then tested for shear-bond strength on the Instron machine. The results
      were that there was no significant difference found between the treated teeth
      when tested for shear-bond strength. However, according to the site of the
      fracture, the stair-step chamfer technique gave significantly better results. It
      can be concluded that, the stir-step chamfer technique provides the clinician
      better environment to place a composite resin restoration resulting in good shear
      bond strength and better esthetics.

PMID- 11990048
TI  - Effect of multiple application of dentin bonding agent on marginal integrity of
      resin composite.
AB  - The purpose of the present study was to examine the effect of multiple
      application of dentin bonding agent to the adhesive surface on the marginal
      integrity of resin composite. The effect of multiple applications was evaluated
      by measuring the wall-to-wall polymerization contraction gap and by SEM
      observation. Multiple application of dentin bonding agent was found to prevent
      formation of the contraction gap. Although monomer penetration into the enlarged
      collagen network has been widely discussed as the possible mechanism of the
      dentin bonding agent and dentin primer, the true detailed mechanism of the
      dentinal bonding agent and dentin primer should be consistently explained by the
      prevention of monomer diffusion into the dentin and water contamination of the
      adhesive interface.

PMID- 11990049
TI  - Microleakage of composite resin restoration in cavities prepared by Er,Cr:YSGG
      laser irradiation and etched bur cavities in primary teeth.
AB  - In this in vitro study, the surface alterations of enamel and dentin in cavities
      prepared by Er,Cr:YSGG laser irradiation was investigated by scanning electron
      microscopy and compared to the microleakage degree after composite resin
      restoration with etched bur cavities in human primary teeth. The results
      confirmed that laser cavity surface facilitated a good adhesion with the
      restorative materials; the acid etch step can be easily avoided with the laser
      treatment.

PMID- 11990050
TI  - Pulpal response to different pulp capping methods after pulp exposure by air
      abrasion.
AB  - Air abrasion is regaining popularity especially in the area of pediatric
      dentistry due to its ease of use and its advantages. Due to the lost of tactile
      information, while using this technique, there is an increased risk for pulpal
      exposure. On the other hand, Ca(OH)2 medicament has been proven to induce dentin
      bridge formation, but an adequate sealing seems to be even more important that
      the capping material used. The purpose of this study was two fold: to assess the
      pulpal response after pulpal exposure by air abrasion and to evaluate the healing
      potential after using Ca(OH)2 medicament or Liner Bond II as a capping agent. Two
      hundred sixteen teeth from mixed-bred dogs were used in this study. The teeth
      were divided into three groups, A) pulpal exposure by air-abrasion followed by
      sealing of the cavity with Liner Bond II, B) pulpal exposure by air-abrasion and
      Ca(OH)2 pulp capping and C) pulpal exposure by high-speed followed by air
      abrasion and Ca(OH)2 pulp capping as a control group. The animals were sacrificed
      after 7, 14, 30 and 60 days and a histopathological evaluation was undertaken.
      After applying Analysis of Variance to compare the groups, it was observed that
      at earlier observation periods, the inflammatory criteria near the exposure site
      were different among the groups. As time elapsed, the inflammation was resolved
      in the pulp tissue, however, the odontoblastic layer and the dentin bridge
      formation had a highly statistically significant difference (p<0.001) among the
      various groups at all observation periods. In addition, a positive correlation
      was observed between the organization of the odontoblastic layer and the dentin
      bridge formation mainly after 30 days. It could be concluded that dentin bridge
      formation could be achieved with the use of Ca(OH) or Liner Bond II as capping
      agent with an adequate sealing. However, the formation is delayed especially when
      Liner Bond II is used as capping agent.

PMID- 11990051
TI  - Electrocoagulation extends the indication of calcium hydroxide pulpotomy in the
      primary dentition.
AB  - The primary molars received calcium hydroxide pulpotomy with or without the
      electrocoagulation procedure. Teeth were evaluated clinically and
      radiographically at 6, 12, and 24 months after treatment. There was no
      statistically significant difference in success rate between calcium hydroxide
      pulpotomies, with and without the electrocoagulation procedure, either clinically
      or radiographically. These results indicate that a pulpotomy with calcium
      hydroxide is an effective treatment for cariously exposed pulp in primary molars
      and electrocoagulation can extend its indication.

PMID- 11990052
TI  - Panoramic radiographic findings of the mandibular growth from deciduous dentition
      to early permanent dentition.
AB  - The outlines of mandibular rami, condyles, coronoid process, and corpus in
      panoramic radiographs of normal children from deciduous to early permanent
      dentition were traced and digitized. Nine linear and four angular measurements
      were measured. During the observation period, the lengths for all the linear
      measurements increased, however, the angles for all the angular measurements
      decreased. The shape of condyle and gonion significantly correlated with the
      growth of ramus and corpus.

PMID- 11990053
TI  - A comparison between zinc polycarboxylate and glass ionomer cement in the
      orthodontic band cementation.
AB  - Fixed orthodontic appliances have been held responsible for demineralization and
      caries since the time they were first introduced. Zinc polycarboxylate and glass
      ionomer cements are the primary materials used in band cementing. In this study,
      we evaluated the re-cementing frequencies, enamel demineralization and the degree
      of cement remains of the bands cemented with glass ionomer and zinc
      polycarboxylate cements. We have concluded that given the retentive properties
      and enamel decalcification degree, the glass ionomer cements are to be preferred
      by the orthodontist.

PMID- 11990054
TI  - Artificial formed caries-like lesions around esthetic restorative materials.
AB  - Dental restorations fail for a variety of reasons. Secondary caries is one of the
      primary causes of failure of dental restorations. One method for reducing
      frequency and severity of this problem is the use of fluoride containing
      restorative materials. The ability of a material to inhibit secondary caries
      formation is an important clinical therapeutic property. This investigation
      assessed the capacity of esthetic restorative materials to resist caries in
      vitro. Class V cavities were prepared in buccal and lingual surfaces of 50
      extracted sound third molars. The occlusal and gingival cavosurface margin of
      each preparation was on enamel surface. The five materials were used:
      Conventional glass ionomer cement Ceramfil beta (PSP), two polyacid modified
      resin composites Compoglass (Vivadent) and Dyract (Dentsply/DeTrey), non fluoride
      releasing composite resin Valux Plus (3M) and fluoride releasing composite resin
      Tetric (Vivadent). After 10 weeks in an acid gel for caries-like lesion
      formation, the teeth were sectioned occluso-gingivally through the middle of the
      restorations and examined by polarized light microscopy, while immersed in water.
      The statistical analysis of the results showed that secondary caries initiation
      and progression might be reduced significantly when fluoride-containing materials
      were placed. The conventional glass ionomer cement (Ceramfil beta) provided the
      highest protection against caries attack and the non-fluoride releasing composite
      resin (Valux Plus) restoration provided the least (p<0.05).

PMID- 11990055
TI  - Density and diameter of dentinal tubules of first and second primary human molars
      -comparative scanning electron microscopy study.
AB  - The aim of the present survey was to evaluate tubule density and diameter of
      dentin of first and second primary human molars and compare the two dental
      categories. These evaluations were done solely at the middle third of the crowns
      of twenty extracted noncarious teeth separated in two groups (first molars and
      second molars). The tubule diameters observed were 0. 794 microm and 1.0 microm
      for first and second molars, respectively (measurements done at 35-65% from the
      pulp-chamber walls). Regarding tubular density, the measurements indicated
      17,997.594 tubules/mm2 and 25,211.317 tubules/mm2 for first and second molars,
      respectively. Comparisons between-groups indicated that tubule diameter and
      density of dentin were higher in second molars, being the difference highly
      significant (P<0.01).

PMID- 11990056
TI  - Seckel syndrome: report of a case.
AB  - An interesting case of a seven years old boy with a combination of clinical,
      genetic, radiological, pathologic and dental findings is presented in view of
      Seckel syndrome literature. General appearance of the patient was characterized
      by small forehead, posteriorly slanted ears, slightly beaked nose, midfacial
      hypoplasia very stunted stature with microcephaly. He had borderline mental
      retardation with normal motor development. Class II dentoskeletal pattern with
      mild overjet and open bite, congenitally missing permanent teeth, microdontia,
      enamel hypoplasia, taurodontism and dentinal dysplasia was observed according to
      the clinical and radiographic examination. In conclusion, Seckel syndrome is not
      encountered routinely in dental clinics, this case illustrates the importance of
      dental care in such a rare condition.

PMID- 11990057
TI  - Garre's osteomyelitis associated with a fistula: a case report.
AB  - A report of Garre's osteomyelitis of the mandible associated with a fistula is
      presented. Elimination of pulpal periapical infection through endodontic therapy
      was shown to be an effective treatment. The total bone healing was observed one
      year later.

PMID- 11990058
TI  - Granular congenital cell tumor in the newborn: a case report.
AB  - This report represents a case of unusual large size congenital granular cell
      tumor appearing on the maxillary alveolar ridge in a newborn. Positive staining
      was found for S-100 protein. The authors discuss the clinical picture,
      histological findings, etiology and treatment of this rare lesion.

PMID- 11990059
TI  - Influence of socioeconomic level and dentifrice brand on the oral hygiene habits
      and the fluoride dentifrice ingestion.
AB  - The aim of this study was to evaluate the influence of socioeconomic level and
      dentifrice brand on the brushing habits and the fluoride ingestion. The sample
      was composed of 124 Brazilian children aged 3-9 years, from different
      socioeconomic levels (SEL). It was used a crossover study with the children using
      two dentifrice brands: Tandy Uva/T (1,100 ppm NaF) and Super Branco/SB (1,500 ppm
      MFP). Each child brushed his/her teeth with both dentifrice brands with weekly
      intervals between the brushes. The oral hygiene habits considered in this study
      were the Dentifrice Amount Placed on toothbrush (ADP), Dentifrice Amount Ingested
      (ADI), Fluoride Amount Ingested (FAI) and Brushing Time (TB). The data obtained
      were submitted to ANOVA test. It was observed that there was influence of SEL on
      the ADP and TB. The high SEL children showed a higher ADP and TB. The dentifrice
      brand influenced significantly the ADP, ADI, AFI and TB; the dentifrice T showed
      a higher ADP, ADI, but a lower AFI and TB. The results showed a significant
      interaction between SEL and dentifrice brand as ADI, AFI and TB. Although the
      children ingested a higher amount of T dentifrice they ingested a higher amount
      of fluoride from the SB dentifrice.

PMID- 11990060
TI  - Drug addiction. Part III. Pharmacotherapy of addiction.
AB  - The last decade brought a considerable progress in pharmacotherapy of addiction.
      Basing on recently gained knowledge of mechanisms of development of addiction and
      the physiology of the brain reward system, several therapeutic strategies have
      evolved. The strategies aimed at targeting the basic mechanisms of addiction rely
      on the premises that addiction is caused by adaptive changes in the central
      nervous system and that craving, which is the main cause of relapse, depends on
      dopaminergic mechanisms and requires high general excitability. The
      pharmacological approach involves drugs that reduce neuronal adaptability by
      inhibiting the calcium entry to neurons both through voltage-gated channels (e.g.
      nimodipine) and NMDA receptors (e.g. memantine), and drugs that stimulate the
      inhibitory GABAergic system (gamma-vinyl-GABA, baclofen), Particular attention is
      paid to the compounds that may attenuate dopaminergic hyperactivity, without
      considerable suppression of tonic activity of dopaminergic neurons (e.g. BP 897,
      a partial dopamine D3 receptor antagonist). Specific strategies are aimed at
      interference with the action of particular drugs of addiction. An important group
      includes the agonistic therapies (known also as substitution or maintenance
      therapies) in which a long-acting agonist is used in order to reduce the action
      of the drugs of high addictive potential (e.g. methadone against heroin addiction
      or vanoxerine (GBR 12909) against psychostimulants). Other specific strategies
      aimed at reduction of the transport of molecules of addictive substances into the
      brain: the approaches involve preparation of antibodies that form complexes
      unable to cross blood-brain barrier or enzymes accelerating the metabolism of the
      compounds in the blood (e.g. variants of butyrylcholinesterase). A considerable
      progress has been made in combating the abuse of legal addictive substances,
      alcohol (naltrexone, acamprosate) and tobacco (bupropion). The prospects for
      developing effective pharmacotherapies against addiction are bright.
      Unfortunately, ideological and social implications, as well as the conflict of
      interest with illegal narcotic manufacturers and distributors, may considerably
      hamper the progress in combating addiction (e.g. difficulties in introduction of
      methadone).

PMID- 11990061
TI  - Behavioral alterations after unilateral 6-hydroxydopamine lesions of the
      striatum. Effect of alpha-tocopherol.
AB  - 6-Hydroxydopamine (6-OHDA) injected unilaterally into the striatum of rats
      induced contralateral circling, and increased the duration of stereotyped
      movements after subcutaneous (sc) injection of apomorphine both 3 and 13 weeks
      after surgery. Ten weeks after surgery, the spontaneous locomotor activity during
      24 h of observation was decreased. Twelve weeks after 6-OHDA injection, the
      animals had difficulties in carrying out a spatial navigation task in the water
      maze when the submerged escape platform was moved to another position on each of
      four consecutive days. When learning to find a new platform position required
      switching behavior-strategies, latency and swim paths were increased because of
      significantly more perseverative crossings of the previous platform positions.
      Intraperitoneal (ip) injection of alpha-tocopherol for 8 days increased the
      ability of naive control animals to find the hidden platform positions in the
      water maze one week later. In intrastriatal sham-operated rats, 8 daily pre
      injections of alpha-tocopherol significantly increased the duration and number of
      bursts of stereotyped movements during 30 min following a sc injection of
      apomorphine if measured 13 weeks after surgery. In 6-OHDA-lesioned rats, alpha
      tocopherol prevented the increased response to apomorphine, reduced the
      apomorphine-induced circling at 3 and 13 weeks, and prevented the decrease in
      spontaneous locomotion at 10 weeks, as well as the perseverative platform
      crossings which are caused by an impairment in switching behavior-strategies in
      the navigation task 12 weeks after surgery. Alpha-Tocopherol has, however, no
      influence on 6-OHDA-induced changes in problem solving strategies. The used model
      reflects some of the pathological symptoms of Parkinson's disease, and it seems
      that alpha-tocopherol may be an effective drug in the early initial stages of the
      disease.

PMID- 11990062
TI  - Serotonin1B receptor ligands in the nucleus accumbens shell do not affect the
      discriminative stimulus effects of amphetamine in rats.
AB  - Enhanced dopamine neurotransmission particularly, in the target area of the
      mesolimbic system, i.e. the nucleus accumbens (NAc), seems to be critical for the
      behavioral effects of amphetamine in rodents. Nonetheless, recent findings have
      also demonstrated a modulatory role of 5-hydroxytryptamine (5-HT; serotonin) in
      these effects. In the present study, we examined whether 5-HT1B receptors in the
      NAc shell are engaged in the discriminative stimulus of amphetamine. To this end
      male Wistar rats were trained to discriminate amphetamine (1 mg/kg, ip) from
      saline (ip) in a two-lever, water reinforced fixed ratio (FR) 20 task. After
      acquiring the amphetamine-saline discrimination, rats were stereotaxically
      implanted with bilateral cannulae aimed at the NAc shell and then infused with
      selective 5-HT1B receptor ligands. The ability of these drugs to substitute for
      or to alter (enhance or antagonize) the discriminative stimulus effects of
      amphetamine was examined. When given systemically, amphetamine (0.125-1 mg/kg)
      produced a dose-dependent increase in drug-lever responding. In substitution
      studies, microinjection of the 5-HT1B receptor agonist CP 93129 (1-10
      microg/side) or the 5-HTIB receptor antagonist GR 55562 (1-10 microg/side) into
      the NAc shell did not evoke amphetamine-lever responding. Combination tests of 5
      HT1B receptor ligands demonstrated that local injection with fixed doses of CP
      93129 (1 or 10 microg/side) or GR 55562 (1 or 10 microg/side) with the submaximal
      doses of amphetamine (0.125-0.5 mg/kg) did not modify dose-response curves of the
      psychostimulant, nor did it affect its ED50 value. Our results seem to exclude a
      role for the NAc shell 5-HT1B receptors in the control of the discriminative
      stimulus effects of amphetamine. These findings also show that pharmacological
      stimulation of those receptors does not affect the amphetamine discrimination in
      rats.

PMID- 11990063
TI  - Implication of the nucleus accumbens shell, but not core, in the acute and
      sensitizing effects of cocaine in rats.
AB  - Expression of cocaine-evoked motor behaviors appears to be dependent on dopamine
      neurotransmission particularly in the target area of the mesolimbic system, i.e.
      the nucleus accumbens (NAc). To test potential anatomical component of the
      locomotor effects of cocaine and expression of its behavioral sensitization, male
      Wistar rats were implanted with bilateral cannulae aimed at the two subregions of
      the NAc (the shell or the core) and then intracranially injected with cocaine
      (locomotor activity) or injected with cocaine given either systemically or
      intracranially following the repeated (5 days) systemic drug administration
      (sensitization). Sensitization was measured at early (5-day) and late (21-day)
      withdrawal periods. Acute administration of intra-NAc shell cocaine (6.73-50
      microg/side) in a dose-dependent manner increased locomotor activity in rats;
      significant hyperactivation was observed after 25 and 50 microg/side of cocaine.
      Intra-NAc core injection of cocaine (12.5-50 microg/side) did not change rats'
      locomotor activity. After 5- or 21-day withdrawal, behavioral sensitization (ca.
      2 times higher locomotor activity than that after acute drug administration) was
      observed when cocaine was injected either systemically (10 mg/kg) or intra-NAc
      shell (12.5-25 microg/side) in animals repeatedly treated with cocaine (10
      mg/kg). No difference was observed in the response to the challenge with intra
      NAc core cocaine (12.5-25 micorg/side) in rats treated repeatedly with cocaine at
      either withdrawal period. The above findings show the differential regulation of
      motor responses to cocaine within the subregions of the NAc. They also indicate a
      preferential effect for the NAc shell in expression of the acute and sensitizing
      effects of cocaine in rats.

PMID- 11990064
TI  - Glucocorticoids modulate behavioral effects induced by dopaminergic agonists in
      rats.
AB  - Studies showing the presence of glucocorticoids, and their binding sites in the
      central nervous system indicate that these hormones may affect central
      neurotransmission. Both, dopaminergic brain system and glucocorticoids are
      considered to be involved in certain psychopathological conditions in humans,
      including depression, addiction or schizophrenia. The present study aimed to
      investigate the influence of glucocorticoids on dopamine agonists-induced
      stereotyped behavior and locomotor hyperactivity in rats. The results of the
      experiment demonstrate that prior to administration of prednisolone (4, 6, 10 or
      20 mg/kg) or dexamethasone (4 or 8 mg/kg) intensified and prolonged the
      stereotypy induced by apomorphine (1 mg/kg sc) or amphetamine (2 mg/kg ip). The
      effect of dexamethasone was more potent. Amphetamine (0.4 mg/kg)- or amantadine
      (50 mg/kg)-induced locomotor hyperactivity was significantly reduced in rats
      pretreated with dexamethasone at a dose of 8 mg/kg or 4 mg/kg. Our observations
      suggest that exogenous glucocorticoids may enhance the activity of the
      dopaminergic agonists in the striatum but reduce it in the mesolimbic system of
      rats.

PMID- 11990065
TI  - Role of serotonergic and noradrenergic systems in a model of visceral pain.
AB  - The effects of selective manipulations of activity of the serotonergic and
      noradrenergic systems were examined in the rat model of visceral pain. It was
      found that neither p-chlorophenylalanine(p-CPA)- nor N-chloro-ethyl-2,2--bromo
      benzylamine(DSP-4)-induced strong and selective depletion of the brain and spinal
      cord serotonin and noradrenaline, respectively, changed in a significant way rat
      visceral pain perception. On the other hand, 8-OH-DPAT, a full selective 5-HT1A
      receptor agonist, prazosin, an alpha1-adrenoceptor antagonist, clonidine, an
      alpha2-adrenoceptor agonist, and two beta-adrenoceptor antagonists: propranolol
      and metoprolol, dose-dependently reduced the number of body writhes induced by
      intraperitoneally administered 2% solution of acetic acid (the writhing test).
      The results obtained with selective receptor ligands, DSP-4 and p-CPA, indicate
      that the noradrenergic and serotonergic innervation of the central nervous system
      contribute in a complex way to the animal behavior in the writhing test. The 5
      HT1A receptors and alpha2-adrenoceptors play an inhibitory role in the expression
      of rat behavior in this model of visceral pain. On the other hand, adrenergic
      alpha1 and beta1 receptors facilitate the behavioral effects of the irritant
      agent.

PMID- 11990066
TI  - Developmental changes in the modulation of cyclic amp accumulation by activation
      of metabotropic glutamate receptors.
AB  - Physiological functions of glutamic acid, the major neurotransmitter in the
      central nervous system, are mediated by the two receptor families: ionotropic
      glutamate receptors (iGluRs), and metabotropic glutamate receptors (mGluRs).
      Eight mGluR subtypes (mGluR1-mGluR8), together with splice variants, have been
      identified and classified into three groups. One of the features of mGluRs is
      their profile of functional expression throughout postnatal development. Several
      lines of evidence suggest age-dependent differences in the pattern or amount of
      mGluR-mediated phosphatidylinositol (P1) turnover as well as in the expression of
      mGluRs. The aim of the present study was to investigate how the different effects
      of mGluR agonists on cAMP accumulation change during rat postnatal life. We have
      found that the stimulatory effect of glutamate and/or 1S,3R-ACPD on cAMP
      accumulation predominates in young animals and decreases in the adults. We have
      also shown that the enhancement of the effect of noradrenaline on cAMP
      accumulation by 1S,3R-ACPD in rats is an age-dependent phenomenon which reaches
      its maximum in 14-30-day-old rats and gradually decreases during their
      maturation. On the basis of our studies, we conclude that the activation of
      mGluRs resulting in cAMP accumulation depends on the age of an animal.

PMID- 11990067
TI  - Effects of indomethacin on hemodynamic parameters after intravenous
      administration of propranolol and enalaprilat in rabbits.
AB  - The aim of the present study was to establish the effect of intravenous
      administration of indomethacin (10 mg/kg), potent inhibitor of prostaglandin
      synthesis, on hemodynamic parametrs after intravenous administration of
      propranolol (0.3 mg/kg) and enalaprilat (0.5 mg/kg) in rabbits. The following
      parameters were estimated: mean arterial blood pressure, heart rate, cardiac
      output and total peripheral resistance. Blood pressure was measured directly in
      the carotid artery, heart rate was counted according to ECG, cardiac output and
      total peripheral resistance were calculated using the method of human 125J
      albumin dilution. For statistical analysis, the average change in the examined
      parametres was calculated. Indomethacin significantly increased mean arterial
      pressure without altering other hemodynamic parameters. Combined intravenous
      administration of indomethacin with enalaprilat or propranolol abolished
      hypotensive effect of both drugs. Indomethacin magnified the effect of
      propranolol on total peripheral resistance and abolished the effect of
      enalaprilat on this parameter. Co-administration of indomethacin with propranolol
      or enalaprilat did not influence significantly heart rate and cardiac output in
      comparison with the effect of both antihypertensive drugs alone. This may
      indicate the predominant role of the influence of indomethacin on vascular tone
      in the observed interaction.

PMID- 11990068
TI  - Differential patterns of cyclosporine A-induced inhibition of humoral and
      cellular immune responses to sheep erythrocytes in mice.
AB  - In this communication we reveal differential inhibitory effects of cyclosporine A
      (CsA) on generation of the cellular and humoral immune responses to sheep
      erythrocytes (SRBC) in mice. For the analysis of the regulatory effects of CsA,
      we analyzed the results of 45 separate experiments performed in recent years
      where CsA served as a reference drug for our research on various immunoregulatory
      compounds. The humoral immune response was determined as the number of plaque
      forming cells (PFC), and the delayed type hypersensitivity (DTH) was measured by
      foot pad swelling. We demonstrated that treatment of mice intraperitoneally (ip)
      with a dose of 100 microg of CsA/mouse, 2 h after immunization resulted in a
      differential pattern of inhibition of these two types of the immune response
      depending on the magnitude of the response in a given experiment. In the case of
      the antibody response (mean number of PFC 2312 median 2200), high PFC numbers
      were inhibited stronger than low ones; mean values in respective quarters and
      inhibitory actions were the following: 1,552 (42.3%), 2,049 (52.4%), 2,441
      (61.2%) and 3042 (62.5%). In consequence, high, medium and low responses were
      down-regulated to approximately the same level. Another inhibitory pattern was
      observed in the DTH model (mean 10.35 units, median 10.8 units), i.e. low DTH
      responses were suppressed more strongly than high ones. The mean DTH responses
      and suppression effects in respective quarters were: 7.4 (58.2%), 10.1
      (52.7%),11.8 (51.8%) and 13.1 (38.8%). As the result of such CsA action, the DTH
      response profile was parallel to that of the control response. In summary, the
      humoral immune response was down-regulated by CsA proportionally to the immune
      response observed in control mice, while DTH response was inversely proportional.
      The possible mechanisms of the observed regulatory CsA actions are discussed.

PMID- 11990069
TI  - 2-H- and 2-acyl-9- [omega-[4-(2-methoxyphenyl)piperazinyl]-alkyl]-1,2,3,4
      tetrahydro-beta-carbolines as ligands of 5-HT1A and 5-HT2A receptors.
AB  - Three series of new unsubstituted or 2-acyl 1,2,3,4-tetrahydro-beta-carbolines
      (THBC), connected to 1-(o-methoxyphenyl)piperazine by 2-, 3- or 4-membered
      alkylene spacer (3, 4 or 5, respectively) in position 9, were synthesized and
      their 5-HT1A/5-HT2A receptor affinities and functional in vivo activities were
      investigated. Radioligand binding studies showed that unsubstituted (a) and acyl
      (b-f) derivatives with prop-1,3-ylene (4) and particularly with but-1,4-ylene (5)
      spacer had a high 5-HT1A receptor affinity (Ki = 30-110 nM), whereas the 5-HT1A
      affinity of derivatives with ethylene spacer (3) was low. All those compounds
      (except 5c, Ki = 44 nM) did not distinctly bind to 5-HT2A receptors. The obtained
      results indicated that the length of an alkylene chain was a crucial parameter
      for determining 5-HT1A receptor affinities of the tested compounds, while acyl
      substituents in position 2 of THBC were not important for their 5-HTIA/5-HT2A
      activities. It was also demonstrated that the few selected compounds (4d, 5a-c
      and 5e) with the highest affinity (Ki up to 50 nM) for 5-HT1A receptors,
      administered at doses of 10-20 mg/kg, behaved like antagonists of postsynaptic 5
      HT1A receptors, as they reduced the 8-OH-DPAT (5-HT1A agonist)-induced lower lip
      retraction and behavioral syndrome in rats. Moreover, 4d seemed to be an agonist
      of presynaptic 5-HT1A receptors, since the hypothermia induced by its
      administration was attenuated by WAY 100635 (5-HT1A antagonist). Compound 5c, 5
      HT2A receptor ligand, demonstrated an antagonistic activity, as it inhibited the
      (+/-)DOI (5-HT2A agonist)-induced head twitches in mice. The obtained results of
      in vivo studies suggest that introduction of different acyl substituents in
      position 2 of THBC with propylene or butylene spacer between tricyclous and
      arylpiperazine moiety is insignificant for the postsynaptic 5-HTIA receptor
      activity of the compounds tested in vivo. On the other hand, only compound 5c
      with an acryloyl group and a butylene chain behaved like a 5-HT1A/5-HT2A
      antagonist.

PMID- 11990070
TI  - Locomotor hypoactivity and motor disturbances--behavioral effects induced by
      intracerebellar microinjections of dopaminergic DA-D2/D3 receptor agonists.
AB  - In the light of recent findings, DA-D3 dopamine receptors with an unclear
      physiological function are present in the cerebellar cortex. Our preliminary
      results seem to indicate that bilateral injection of 7-OH-DPAT, a DA-D2/D3
      receptor agonist (1 and 10 microg/0.5 microl), to lobule 9/10 of rat cerebellar
      cortex reduces spontaneous locomotor activity (hypolocomotor effects) and induces
      balance and motor coordination disturbances, respectively. Similar effects can be
      observed in the case of analogous microinjection of the DA-D3/D2 agonist
      pramipexole. In earlier studies, peripheral (ip) injection of nafadotride (0.6
      mg/kg), a D3 receptor antagonist, neither affected per se spontaneous motor
      activity, nor modified the above described effects of 7-OH-DPAT. Participation of
      cerebellar DA-D3 and DA-D2 receptors in hypolocomotor effects, as well as
      putative participation of other receptors in the generation of motor
      disturbances, has been discussed.

PMID- 11990071
TI  - Effects of anxiolytic drugs on some behavioral consequences in olfactory
      bulbectomized rats.
AB  - The present study was designed to evaluate the effects of bulbectomy and acute
      administration of anxiolytic drugs (diazepam, 10 mg/kg; chlordiazepoxide, 10
      mg/kg) on the behavior of both sham-operated and olfactory bulbectomized rats in
      two tests predictive of anxiolytic activity: plus-maze test and Vogel's conflict
      test. We investigated also the effect of flumazenil (10 mg/kg), a benzodiazepine
      receptors antagonist, both on control and drug-treated animals. We also evaluated
      behavior of animals in conditioned place aversion procedure. Our results show the
      decreased level of anxiety in bulbectomized animals comparing with sham-operated
      rats. Anxiolytic drugs further deepen this effect.

PMID- 11990072
TI  - Isobolographic analysis of interaction between vigabatrin and baclofen in the
      formalin test in mice.
AB  - Vigabatrin and baclofen given together, at doses not affecting motor performance,
      produced dose-dependent inhibition of both phases in the formalin test in mice.
      Isobolographic analysis revealed a significant synergy between both drugs in both
      phases of the forrmalin test.

PMID- 11990073
TI  - Nociceptive changes in rats after prenatal exposure to valproic acid.
AB  - Abnormalities in anatomy and function of the cranial nerve motor nuclei and brain
      stem structures have been demonstrated in some people with autism and can be
      modeled in rats by exposure to valproic acid (VPA) during very early nervous
      system developmental stages (neural tube closure). The aim of this study was to
      investigate if VPA will have an impact on nociception in rats because of reported
      hypoalgesia in a subgroup of autistic patients. Pregnant females were treated ip
      with 600 mg/kg of sodium valproate on day 12.5 of gestation. Nociception was
      measured in offsprings by tail-flick and thermal paw withdrawal tests in two
      developmental stages: prepubertal (80-90 g) and adulthood (360-440 g). Results
      showed significant differences in pain sensitivity with hypoalgesia in male rats
      treated with VPA compared to male control in both developmental stages. The
      outcome of our study suggests that rats exposed prenatally to VPA show
      abnormalities in nociception similar to those observed in human autistic
      patients. Interestingly, naloxone (1 mg/kg) had no impact on nociception in
      offsprings of VPA-treated rats.

PMID- 11990074
TI  - Comparative investigations of hydroxyamine carane derivative and its R,S
      diastereoisomers with strong local anesthetic activity.
AB  - Our previously conducted pharmacological screening led as to the discovery of the
      strong local anesthetic activity of the compound designated as KP-23. Earlier
      crystallographic studies revealed that the compound KP-23 crystallized in
      diastereoisomeric form in lowest symmetry. The aim of these comparative
      investigations was to evaluate anesthetic activity of KP-23 and its R,S
      diastereoisomers, which were synthesized at the Institute of Organic Chemistry,
      Biochemistry and Biotechnology, Wroclaw University of Technology.

PMID- 11990075
TI  - Immunoreactivity in kainate model of epilepsy.
AB  - Seizure-related changes in function of the peripheral immune system, especially
      in its cell component are poorly recognized. In the present study, we examined
      the effect of seizures induced by intraperitoneal injection of kainate to mice
      and rats on weight of central and secondary immunological organs and metabolic
      activity of splenocytes (MTT test). In kainate-injected mice the production of
      cytokines: interleukin 2 (IL-2) and IL-10 was also estimated. Seventy two hours
      after kainate administration, the mice and rats showed a marked decrease in the
      thymus weight by 36% and 50%, respectively, whereas the spleen weight tended to
      decrease in rats only. Splenocytes of kainate-injected mice and rats showed
      significant increase in metabolic activity. The ability of splenocytes of kainate
      injected mice to produce IL-2 and IL-10 was reduced but only the former effect
      reached statistical significance. The results suggest a decrease in T helper-cell
      dependent immunoreactivity and enhanced phagocytic activity of macrophages in
      kainate-treated rodents.

PMID- 11990076
TI  - Repeated treatment with SA4503, a selective sigma1 receptor agonist, up-regulates
      alpha-adrenergic system. a behavioral study.
AB  - The obtained results indicate that SA4503, a selective sigma1 receptor agonist,
      given repeatedly (but not acutely) enhanced the effects of phenylephrine, alpha1
      adrenoceptor agonist, and clonidine (stimulating the postsynaptic alpha1
      adrenoceptors at high dose) in behavioral models (hyperexploratory activity in
      rats and aggressiveness in mice, respectively).

PMID- 11990077
TI  - Drug addiction. Part II. Neurobiology of addiction.
AB  - The drug addiction may be regarded as the disease of the brain reward system.
      This system, closely related to the system of emotional arousal, is located
      predominantly in the limbic structures of the brain. Its existence was proved by
      demonstration of the "pleasure centers," that were discovered as location from
      which electrical self-stimulation is readily evoked. The main neurotransmitter
      involved in the reward is dopamine, but other monoamines and acetylcholine may
      also participate. The anatomical core of the reward system are dopaminergic
      neurons of the ventral tegmentum that project to the nucleus accumbens, amygdala,
      prefrontal cortex and other forebrain structures. Several of those structures may
      be specifically involved in the reward produced by different substances, when
      anticipating the reward. The recent discovery of CART peptides may importantly
      expand our knowledge about the neurochemistry of reward. Natural rewarding
      activities and artificial chemical rewarding stimuli act at the same locations,
      but while natural activities are controlled by feedback mechanisms that activate
      aversive centers, no such restrictions bind the responses to artificial stimuli.
      There are several groups of substances that activate the reward system and they
      may produce addiction, which in humans is a chronic, recurrent disease,
      characterized by absolute dominance of drug-seeking behavior. The craving induced
      by substances of addiction inhibits other behaviors. The adaptation of an
      organism to a chronic intake of drugs involves development of adaptive changes,
      sensitization or tolerance. It is thought that the gap between sensitization
      developing for the incentive value of the drug and tolerance to the reward
      induced by its consumption underlies the vicious circle of events leading to drug
      dependence. The vulnerability to addiction is dependent not only on the
      environment, but also on genetic factors.

PMID- 11990078
TI  - Amphetamine-induced enhancement of neostriatal in vivo microdialysate dopamine
      content in rats, quinpirole-primed as neonates.
AB  - Amphetamine (AMPH)-induced sensitization of central dopamine (DA) receptors,
      produced by repeated AMPH treatments, is associated with increased AMPH-induced
      DA release in the rat forebrain. However, for DA receptor sensitization produced
      by repeated DA receptor agonist treatments, the effects on forebrain DA release
      are not known. The objective of our study was to determine this. DA receptor
      sensitization was produced by administering the DA D2 agonist quinpirole (50
      microg/kg/day) to rats, from the 1st to 11th days after birth - a process known
      as 'priming'. When these rats were tested at 3 months, DA receptor sensitization
      was manifested as increased quinpirole-induced yawning. We also found that AMPH
      (1.0 mg/kg, ip) acutely induced a 5-fold greater increase in DA content in the
      neostriatal in vivo microdialysate of these quinpirole-primed rats (vs.
      controls), accompanied by a reduction in dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) levels in the microdialysate. Conversely, an acute
      injection of quinpirole x HCl (100 microg/kg, ip) reduced the microdialysate
      contents of DA, DOPAC and HVA to comparable levels in quinpirole-primed and
      control rats. Therefore, we can conclude that long-lived DA receptor
      sensitization, produced by repeated DA D2 agonist treatments in ontogeny, is
      associated with enhanced AMPH-induced DA release in the neostriatum in adulthood,
      but is not accompanied by evident alteration in quinpirole-induced DA release.

PMID- 11990079
TI  - NMDA receptor antagonists change behavioral activity of rats treated with (S)
      4CPG.
AB  - The effect of (S)-4CPG [(S)-4-carboxyphenylglycine] (25, 50, 100 nmol icv) and
      the effect of AP-7 (5 nmol icv) or MK-801 (5 nmol icv) on the processes of
      acquisition, consolidation of conditioned reflexes and locomotor activity were
      tested in rats. Neither AP-7, MK-801 nor (S)-4CPG given alone changed locomotor
      activity. MK-801 significantly increased the effects of (S)-4CPG: on crossings at
      all applied doses, on rearings at 100 nmol, and on bar approaches at 50 nmol of
      (S)-4CPG. AP-7 enhanced the effects of 50 and 100 nmols of (S)-4CPG on crossings,
      100 nmol of (S)-4CPG on rearings in the open field test. Neither AP-7, MK-801 nor
      (S)-4CPG at doses of 50 and 100 nmols influenced acquisition, but (S)-4CPG given
      alone at a dose of 25 nmol impaired acquisition. MK-801 impaired the action of 50
      and 100 nmols of (S)-4CPG on acquisition. AP-7 only at a dose of 100 nmol
      inhibited (S)-4CPG-induced acquisition. Neither AP-7, MK-801 nor (S)-4CPG given
      alone changed consolidation in passive avoidance situation while co
      administration of AP-7 and (S)-4CPG at the doses of 50 and 100 nmols, affected
      this process. The obtained results support our hypothesis concerning the co
      operation between group I mGluRs and NMDA receptors in some behavioral tests and
      the modulating effect of group I mGluRs antagonist on central action of NMDA
      receptor antagonists.

PMID- 11990080
TI  - Effect of cyclooxygenase and NO synthase inhibitors on antinociceptive action of
      acetaminophen.
AB  - The influence of cyclooxygenase (COX) and NO synthase inhibitors on
      antinociceptive action of acetaminophen (ACETA) was studied in rats. ACETA
      increased the nociceptive threshold for both mechanical (Randall-Selitto test)
      and chemical stimuli (writhing test). In both models the existence of ceiling
      dose of ACETA was observed. Indomethacin (IND), an inhibitor preferentially
      acting on COX-1, as well as nimesulide (NIM) and celecoxib (CECOX), i.e.
      respectively preferential and selective inhibitors of COX-2, markedly decreased
      the antinociceptive activity of ACETA in Randall-Selitto test. In contrast, IND
      increased, whereas both NIM and CECOX did not have any effect on ACETA action in
      writhing test. Pretreatment with LG-nitro-L-arginine (L-NO-ARG), an unspecific
      inhibitor of NO synthase, 7-nitroindazole (7-NI), relatively specific inhibitor
      of neuronal NO synthase, and L-N6(1-iminoethyl)lysine (L-NIL), relatively
      selective inhibitor of inducible NO synthase, significantly increased the action
      of the lower doses of ACETA (50 and 100 mg/kg) in writhing test, whereas it did
      not modify the effects of the higher doses. Similar effect of L-NO-ARG and 7-NI
      was observed in Randall-Selitto test, whereas L-NIL did not influence the action
      of ACETA. The possible involvement of COX and NO synthase systems in
      antinociceptive activity of ACETA is discussed.

PMID- 11990081
TI  - Effects of antidepressant drugs on the activity of cytochrome P-450 measured by
      caffeine oxidation in rat liver microsomes.
AB  - Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation)
      in humans and rats. Moreover, it is also a relatively specific substrate of CYP3A
      (8-hydroxylation). In the case of 1-N- and in particular 7-N-demethylation of
      caffeine, apart from CYP1A2, other cytochrome P-450 isoenzymes play a
      considerable role. The aim of the present study was to investigate the influence
      of imipramine, amitriptyline and fluoxetine on cytochrome P-450 activity measured
      by caffeine oxidation in rat liver microsomes. The obtained results showed that
      imipramine exerted a most potent inhibitory effect on caffeine metabolism.
      Imipramine decreased the rate of 3-N-, 1-N- and 7-N-demethylations, and 8
      hydroxylation of caffeine, the effect on 3-N-demethylation being most pronounced
      (Ki = 33 microM). Amitriptyline showed distinct inhibition of 3-N- and 1-N
      demethylation of caffeine, though its effect was less potent than in the case of
      imipramine (Ki = 57 and 61 pM, respectively). The influence of amitriptyline on 8
      hydroxylation and especially on 7-N-demethylation of caffeine was weaker (Ki =
      108 and 190 pM, respectively) than on 3-N- or 1-N-demethylation, suggesting a
      narrower spectrum of cytochrome P-450 inhibition by amitriptyline than by
      imipramine, involving mainly the subfamily CYP1A2, and--to a lesser degree-
      CYP3A. In contrast to the tested tricyclic antidepressants, fluoxetine did not
      exert any considerable effect on the 3-N- or 1-N-demethylation of caffeine (Ki =
      152 and 196 microM, respectively), which indicates its low affinity for CYP1A2.
      However, fluoxetine displayed a clear inhibitory effect on caffeine 7-N
      demethylation (Ki = 72 microM), the reaction which is catalyzed mainly by other
      than CYP1A2 isoenzymes. Fluoxetine diminished markedly the 8-hydroxylation of the
      marker drug; as reflected by Ki values, the potency of inhibition of rat CYP3A by
      fluoxetine was similar to that of imipramine (Ki = 40 and 45 microM,
      respectively). In summary, CYP1A2 was distinctly inhibited by imipramine and
      amitriptyline, CYP3A by imipramine and fluoxetine, while other CYP isoenzymes
      (CYP2B and/or 2E1) by imipramine and fluoxetine.

PMID- 11990082
TI  - Synthesis, 5-HT1A and 5-HT2A receptor activity of new 1-phenylpiperazinylpropyl
      derivatives with arylalkyl substituents in position 7 of purine-2,6-dione.
AB  - A series of new 1,3-dimethyl-7-phenylalkyl-8-[3-(4-phenyl-1
      piperazinyl)propylamino]-purine-2,6-dione derivatives (10-16) was synthesized and
      their 5-HTIA and 5-HT2A receptor affinities were determined. It was found that
      compounds with the phenylpropyl substituent in position 7 of purine-2,6-dione
      (12, 14 and 16), or with phenylmethyl in position 7 and 2-OCH3 in the
      phenylpiperazine part (13) showed a distinct affinity for 5-HTIA receptors (Ki =
      8-50 nM). No structural modifications resulted in 5-HT2A ligands, since the
      affinity of 10-16 for those receptors was insignificant (Ki = 115-550 nM). The
      new 5-HT1A receptor ligands (12-14, 16) were investigated in vivo to determine
      their functional activity at those receptors. In behavioral studies, 12-14 and 16
      behaved like postsynaptic 5-HTIA receptor antagonists, since they reduced lower
      lip retraction and the behavioral syndrome induced by 8-OH-DPAT (5-HT1A receptor
      agonist) in rats. When given alone, none of the compounds investigated in vivo,
      mimicked 8-OH-DPAT activity in those tests. Derivative 12 did not affect the body
      temperature in mice, whereas 13, 14 and 16 decreased it. Furthermore, 12 did not
      change the hypothermia induced by 8-OH-DPAT, and the decrease in body temperature
      in mice induced by 13, 14 or 16 was not antagonized by WAY 100635 (5-HT1A
      receptor antagonist); hence in that model neither 12, 13, 14 nor 16 acted as
      antagonists or agonists, respectively, at presynaptic 5-HT1A receptors.

PMID- 11990083
TI  - Substitution mode of the amide fragment in some new N-[omega-[4-(2
      methoxyphenyl)piperazin-1-yl]alkyl]pyrid-2(1H)-ones and their 5-HT1A/5-HT2A
      activity.
AB  - A series of omega-[4-(2-methoxyphenyl)piperazin-1-yl]alkyl derivatives with
      terminal pyrid-2(1H)-one fragments was synthesized and evaluated for their 5-HTIA
      and 5-HT2A activity. Enlargement of the aromatic amide system by its substitution
      with phenyl and/or p-methoxyphenyl in positions 4, 5 and/or 6, as well as
      modification of an aliphatic spacer allowed us to better understand structure
      activity relationships in that group of compounds. The results of in vitro and in
      vivo experiments showed that only unsubstituted (1b) and monosubstituted (2b-4b)
      derivatives with the tetramethylene spacer demonstrated high 5-HTIA receptor
      affinity (Ki = 15-40 nM) and 5-HT1A/5-HT2A selectivity; they exhibited features
      of 5-HTIA antagonists. Those results suggested that the mode of substitution of
      the terminal amide moiety in the tested tetramethylene arylpiperazines was not
      significant for their 5-HTIA receptor activity. Conformational analysis
      calculations indicated that despite its great capacity for adaptation at 5-HTIA
      receptor site, an aryl substituent in position 4 in the pyrid-2(1H)-one ring
      destabilized the ligand-5-HT1A receptor complex formation in the case of
      trimethylene derivatives. Diarylsubstituted derivatives (5a-8a and 5b-8b) were
      characterized by a low 5-HT2A affinity (Ki > 446 nM) regardless of the spacer
      length, while those with the tetramethylene aliphatic chain had a higher 5-HT2A
      affinity than the remaining investigated compounds.

PMID- 11990084
TI  - Immunotropic activity of vratizolin (ITCL, Denotivir).
AB  - The aim of this study was to evaluate immunotropic properties of vratizolin, a
      known antiviral drug, in several in vitro and in vivo assays in mouse and human
      models. We demonstrated that vratizolin exerted strong immunosuppressive actions
      both in the humoral and cellular immune response to SRBC in mice. The compound
      affected not only the inductive phase of delayed type hypersensitivity (DTH) but
      also the effector phase of that response. Vratizolin was effective when given
      intraperitoneally and orally. The inhibitory action of vratizolin was comparable
      to that of cyclosporin A (CsA), the reference drug. Vratizolin exhibited also
      suppressory properties with regard to PHA-induced proliferation of human
      peripheral blood lymphocytes and that effect exceeded the inhibitory action of
      CsA. We also showed that vratizolin inhibited to some degree LPS-induced cytokine
      production in human peripheral blood cultures. The activities of TNF-alpha, IL-1
      and IL-6 were inhibited on average by 37, 26 and 35%, respectively. This was in
      contrast to the effects of CsA which strongly inhibited only IL-1 production.
      Lastly, we demonstrated that vratizolin markedly inhibited growth of several
      tumor cell lines. In particular, the compound significantly inhibited growth of
      mouse leukemia L-1210 and human acute lymphoblastoid leukemia CCRF-CEM cell
      lines. The presented data suggest that the immunosuppressory action of
      vratizolin, although similar to that of CsA, is mediated by a different
      mechanism. The properties of vratizolin, described in this report, indicate that
      the drug should be further investigated for possible immunosuppressory and
      antitumor application.

PMID- 11990085
TI  - Rapid down-regulation of GABA-A receptors after pretreatment of mice with
      progesterone.
AB  - The effect of a single administration of a high dose of progesterone on brain
      [3H]muscimol binding, was examined in mice using quantitative autoradiography. It
      was found that progesterone given at the dose of 150 mg/kg ip (the ED85 dose
      established previously in the model of picrotoxin seizures, Czlonkowska et al.,
      Pharmacol. Biochem. Behav., 2000, 67, 345-353), significantly decreased the
      specific binding of [3H]muscimol to the nucleus caudatus and nucleus accumbens,
      as early as 1 h after injection. A similar tendency, close to the statistically
      significant level, was also present in the dentate gyrus of the hippocampus (p =
      0.07). It is suggested that a high dose of progesterone and ensuing excessive
      stimulation of GABAA receptors by its metabolites, neurosteroids, could bring
      about rapid changes in the GABAA receptor number and/or affinity.

PMID- 11990086
TI  - Effects of histamine on phosphoinositide metabolism in chick cerebral cortex.
AB  - Effects of histamine (HA) and agonists of HA receptors on phosphoinositide
      metabolism in chick cerebral cortex have been studied using two approaches -
      measurement of inositol 1,4,5-trisphosphate (IP3) level by a specific and
      sensitive IP3 receptor radioassay, and analysis of [3H]inositol phosphates
      accumulation in cortical slices prelabeled with myo-[3H]inositol. HA
      concentration-dependently elevated IP3 levels in slices of chick cerebral cortex.
      The effect of HA was mimicked by 2-methylHA, a selective agonist of H1-HA
      receptors, and blocked by mepyramine, an H1 receptor antagonist. 4-MethylHA and
      Ralpha-methylHA, selective agonists of H2- and H3-HA receptors, respectively, did
      not affect IP3 level in the chick cerebrum. In cerebral cortical slices
      prelabeled with myo-[3H]inositol, 2-methylHA significantly stimulated
      [3H]inositol phosphates accumulation, whereas HA only slightly and non
      significantly increased phosphoinositide metabolism. It is suggested that
      phospholipase C-coupled H1-HA receptors are present in the chick cerebral cortex,
      yet their number seems to be a small one.

PMID- 11990087
TI  - Arylpiperazine derivatives of 3-propyl-beta-tetralonohydantoin as new 5-HT1A and
      5-HT2A receptor ligands.
AB  - A series of new analogues of 3-[3-(4-arylpiperazinyl)-propyl]-cyclo-hexane-1',5
      spirohydantoin (2), with aromatic ring fused in amide moiety (4-9) were
      synthesized and evaluated for affinity at 5-HTIA and 5-HT2A receptors. The
      influence of the substitution mode in the phenyl ring of phenylpiperazine moiety
      on the affinity for both receptors has been discussed. The most potent 5-HTIA (9,
      Ki = 53 nM) and 5-HT2A (4, 6, 8 and 9; Ki = 14-76 nM) ligands were evaluated in
      in vivo tests. The obtained results indicate that all in vivo tested compounds
      showed pharmacological profile of 5-HT2A antagonists. Additionally, a m-CF3
      derivative (9), behaved like a partial agonist (agonist of pre- and antagonist of
      postsynaptic) of 5-HTIA receptors and may offer a new lead for the development of
      potential psychotropic agents.

PMID- 11990088
TI  - Effect of physiological and pharmacologically induced thymus involution on the
      immunoreactivity in C57BL mice.
AB  - The effect of physiological and pharmacologically induced thymus involution was
      studied in 12-week-old female C57BL mice. Thymus involution was estimated by
      measurement of the thymus weight and the ability of thymocytes to induce a graft
      versus-host (GvH) reaction at 48 h after delivery or drug administration in
      comparison with control (virgin, saline-treated) mice. The thymus weight and
      immunoreactivity of thymocytes after delivery were reduced in a statistically
      significant manner by ca. 80 and 75%, respectively. On the other hand,
      hydrocortisone administration decreased the thymus weight (by ca. 60%), but did
      not change the ability of thymocytes to induce a GvH reaction. Cyclophosphamide
      administration significantly reduced both the thymus weight and the reactivity of
      thymocytes. The present study suggests that the transient thymus involution
      observed after delivery, connected with a loss of the ability of thymocytes to
      induce a GvH reaction, cannot be explained merely by elimination of a steroid
      sensitive cortical cell population, since the GvH reactivity of thymocytes was
      preserved in hydrocortisone-treated mice.

PMID- 11990089
TI  - Attitudes toward medical aid to developing countries.

PMID- 11990090
TI  - Snake bite by Cerastes vipera in children: report of two cases.
AB  - Two children, ages 2 and 4 years, envenomed by the snake Cerastes vipera are
      presented. Both children suffered from local pain and swelling of the hand that
      spread up to the shoulder in the 2-year-old and up to the elbow in the 4-year
      old. A hemorrhagic blister was noted on the bitten finger in the younger patient.
      Urinary retention, tachycardia, and a slight prolongation of prothrombin time was
      noted in the 2-year-old, whereas hypertension and fever were observed in the 4
      year-old. In both cases, the swelling receded gradually and the patients were
      discharged from the hospital after several days without any complications and in
      a good condition.

PMID- 11990091
TI  - Serum potassium concentration as a predictor of resuscitation outcome in
      hypothermic cardiac arrest.
AB  - The purpose of this study was to determine whether serum potassium concentration
      (SK) can predict resuscitation outcome in a canine model of severe hypothermic
      cardiac arrest. Fifteen adult mongrel anesthetized dogs were immersed to the neck
      in a 4 degrees C water bath and ventilated with room air, with ventilation halved
      at 45 min and stopped at 90 min. After cardiac arrest, 14 of the dogs were kept
      in the water bath for periods of 2-7 h, and another was held in arrest for 13 h.
      Following 10 min of closed chest cardiopulmonary resuscitation (CPR) (simulating
      a short transport time to a hospital), animals were placed on cardiopulmonary
      bypass and rapidly rewarmed. With appearance of ventricular fibrillation, animals
      were defibrillated up to three times. Standard advanced cardiac life support was
      initiated at a core temperature (Tc) of 30 degrees C. Eight of the 15 dogs had
      return of spontaneous circulation (ROSC), at Tc ranging from 30.4 to 36.5 degrees
      C. The eight dogs with ROSC did not differ from the seven without ROSC in time to
      arrest (128 +/- 48 versus 128 +/- 23 min) (mean +/- SD) or Tc at arrest (18.1 +/-
      2.2 versus 17.9 +/- 3.1 degrees C), but had higher Tc at the end of the arrest
      period (9.7 +/- 3.0 versus 5.2 +/- 2.0 degrees C), reflecting a shorter arrest
      period in the dogs with ROSC (225 +/- 95 versus 420 +/- 193 min). SK (mEq liter(
      1)) did not differ between dogs with and without ROSC at baseline (3.5 +/- 0.4
      versus 3.7 +/- 0.4) or at arrest (3.4 +/- 0.7 versus 4.3 +/- 2.2), but there was
      a trend toward higher SK at the end of arrest in the group without ROSC (4.6 +/-
      1.5 versus 9.4 +/- 6.3; range 3.2-7.8 versus 3.5-21.4; p = .053). SK was similar
      after 10 min of CPR in the groups with and without ROSC (6.6 +/- 2.9 versus 9.0
      +/- 2.4; range 2.5-11.1 versus 4.5-11.0; p = .107). SK after 10 min of CPR was
      higher in some animals with ROSC (9.6 and 11.1) than in others which did not have
      ROSC (4.5 and 7.9). We conclude that very high SK following prolonged hypothermic
      cardiac arrest may be suggestive of an inability to resuscitate. However, SK
      after both prolonged hypothermic cardiac arrest and a brief period of CPR is not
      a good predictor of resuscitation using cardiopulmonary bypass rewarming in an
      animal model.

PMID- 11990092
TI  - Emergency mechanical ventilation at moderate altitude.
AB  - Portable emergency ventilators are commonly used in the prehospital setting in
      the transport of critically ill patients in hypobaric environments. The aim of
      our trial was to evaluate the influence on minute ventilation and blood gas
      analysis of moderate altitude (3000 m) compared to 171 m in healthy volunteers
      during mechanical ventilation with the Draeger Oxylog ventilator. At 3000 m, the
      delivered minute volume increased by 9.8% in the air mix mode and by 14.6% in the
      no air mix mode. PaO2 at 3000 m altitude decreased by 33.3% in the air mix mode,
      and no statistical change was observed in the no air mix mode. PaCO2 at 3000 m
      altitude decreased by 9.0% in the air mix mode and by 12.8% in the no air mix
      mode. These changes are of sufficient magnitude and importance to require
      monitoring of minute volume to prevent barotrauma or volume-related trauma and to
      monitor oxygenation by pulse oximetry during emergency mechanical ventilation at
      moderate altitude.

PMID- 11990093
TI  - Ciguatera poisoning after ingestion of imported jellyfish: diagnostic application
      of serum immunoassay.
AB  - Ciguatera fish poisoning is an important public health problem wherever humans
      consume tropical and subtropical fish. It accounts for over half of fish-related
      poisonings in the United States but is uncommonly diagnosed and underreported.
      Produced by dinoflagellates, ciguatoxin accumulates up the food chain in
      herbivorous and carnivorous fishes. Cnidaria jellyfish and related invertebrates)
      have not previously been associated with direct ciguatera intoxication in humans.
      We report the first case of ciguatera fish poisoning associated with cnidarian
      ingestion. A 12-year-old Tongan female presented to our Emergency Department with
      mid-abdominal pain, nausea, change in mental status, and new-onset movement
      disorder after ingestion of jellyfish imported from American Samoa. Clinical
      diagnosis was confirmed by strongly positive serum identification of ciguatoxin
      and related polyether toxins (including okadaic acid) with a rapid extraction
      method (REM) and highly reliable solid-phase immunobead assay (S-PIA) performed
      by the Food Toxicology Research Group, University of Arizona. Ciguatera
      pathophysiology, clinical presentation, differential diagnosis (including
      consideration of palytoxin poisoning), and treatment are briefly reviewed. We
      emphasize the growing incidence of ciguatera fish poisoning outside "high-risk"
      areas. In regions with immigrant populations, privately imported exotic fish may
      be toxin vectors. Marine species other than carnivorous fish are now suspect in
      human ciguatera intoxication. Reliable tests can aid in premarket fish testing,
      diagnosis, and follow-up of ciguatera fish poisoning. The global prevalence of
      marine toxins demands fishermen, consumers, and physicians maintain a high index
      of suspicion for ciguatera fish poisoning.

PMID- 11990094
TI  - Influence of cold water immersion on heat debt and substrate utilization in males
      varying in body composition: a retrospective analysis.
AB  - The present article is a retrospective analysis of previously published data.
      This analysis examined the effect of immersion in 18, 22 and 26 degrees C cold
      water, on heat debt (kJ), substrate utilization [i.e., R (respiratory exchange
      ratio) calculated using indirect calorimetry], and aerobic metabolic rate (i.e.,
      VO2 (oxygen consumption) 1 # min(-1)] in 24 male volunteers (20-35 years) given a
      preexposure meal (60.2 g carbohydrate, 12.0 g protein, and 2.8 g fat at 60 min
      prior to the experimental trial) and examined during 90 min of immersion to the
      first thoracic vertebrae. Body composition was determined via underwater
      densitometry. Subjects were divided with respect to high body fat (HF; 18-22%, n
      = 12) or low body fat (LF; 8-12%, n = 12) and randomly assigned to one of three
      water temperatures. Body heat debt and R did not differ between the LF or HF
      groups, between temperatures, or across time. Percent calories utilized indicated
      that for these experimental conditions the predominant substrate utilized between
      the LF and HF groups across time was derived from carbohydrate. In addition, VO2
      was greater (p = .0004) in the LF than HF group, and the latter was greater (p =
      .0013) in the 18 degrees C group versus the 26 degrees C group and increased
      across time (p = .0001); that is, VO2 after 5 min of immersion was less than at
      60 and 90 min, and values obtained after 30 min of immersion were less than those
      at 90 min of immersion. Based on these data, it appears that the LF group would
      expend more calories (308.9 vs. 199.9 kcal, respectively) and more likely derive
      these calories from a carbohydrate source than the HF group during 90 min of cold
      water immersion. It would appear beneficial to consider a feeding supplement for
      the low-fat individual if immersion was in a more thermal stressful environment
      or extended for a protracted period of time.

PMID- 11990095
TI  - Dehydration and pancreatitis in a child lost in the mountains for 2 days.
AB  - An 8-year-old boy became lost while hiking in the Sierra Nevada Mountains of
      northern California in August 1994. He was found 2 days later, at which time he
      was dehydrated and admitted to the hospital for rehydration. After admission, he
      was found to also have mild pancreatitis. Although trauma could not be ruled out
      as the cause of the pancreatitis, the stress associated with being lost is felt
      to be an equally likely etiology.

PMID- 11990096
TI  - Chemotherapy and prevention of drug-resistant malaria.
AB  - Drug-resistant falciparum and vivax malaria will continue to be an increasing
      problem. The incidence of drug-resistant malaria has been increasing at a rate
      that exceeds new drug development. Plasmodium falciparum has rapidly developed
      resistance to new synthetic antimalarials, including mefloquine and halofantrine.
      P. vivax malaria resistant to chloroquine and primaquine is now widespread in
      parts of Oceania; the optimal therapy for this infection is unknown. At present,
      a combination of qinghaosu derivatives and mefloquine appears to be the most
      active drug regimen against multidrug-resistant falciparum malaria from Southeast
      Asia. However, qinghaosu compounds are not yet licensed and widely available. The
      capacity of P. falciparum to rapidly develop drug resistance and the growing
      evidence that other plasmodia can evolve resistance suggests that within the next
      10 years, we face the real prospect of untreatable malaria. Ultimately, control
      of malaria may require more creative approaches than additional inhibitory drugs.
      These might include: the identification of biochemical pathways unique to the
      parasite (such as drug efflux and heme polymerase), making it possible to design
      new classes of antimalarial agents that are selectively toxic to the parasite;
      methods to block parasite development in the mosquito vector; and multistage
      vaccines against both asexual and sexual stages in order to block both the
      pathophysiology and transmission of disease.

PMID- 11990097
TI  - Diplopia at high altitude.

PMID- 11990098
TI  - Helmets on climbers.

PMID- 11990099
TI  - The cliffs of Kalaupapa.

PMID- 11990100
TI  - Doctor, I'm hooked.

PMID- 11990101
TI  - Waterproof wound dressing.

PMID- 11990102
TI  - Climbing after keratorefractive surgery.

PMID- 11990103
TI  - Cardiorespiratory response to free suspension simulating the situation between
      fall and rescue in a rock climbing accident.
AB  - Many factors contribute to the risk of late death after successful rescue in a
      rock climbing accident. One factor may be hemodynamic and respiratory compromise
      by free suspension in a rope between fall and rescue. The risk probably results
      from using a chest harness alone or the combination of a chest harness and a sit
      harness. No trials on the acute cardiorespiratory response to free suspension in
      rock climbing have been reported so far. The effect of 3 min free suspension in a
      chest harness or in a sit harness on cardiopulmonary parameters was investigated
      in a randomized, cross-over trial in six healthy volunteers in a simulated rock
      climbing accident. Measurements were performed before and during the suspension
      at an altitude of 171 m. No statistical change in cardiopulmonary parameters was
      observed after free suspension in the sit harness. After free suspension in the
      chest harness, mean forced vital capacity decreased by 34.3% and mean forced
      expiratory volume decreased by 30.6%. No statistical change of arterial oxygen
      saturation occurred and mean end-tidal carbon dioxide increased by 11.5%. Mean
      heart rate decreased by 11.7%, mean systolic blood pressure decreased by 27.6%,
      mean diastolic blood pressure decreased by 13.1%, and mean cardiac output
      decreased by 36.4%. The p value for all reported changes was <0.05. We conclude
      that free suspension in a chest harness leads to a dramatic impairment of
      hemodynamics and respiration. This may contribute to the risk of a fatal outcome
      if rescue is not timely.

PMID- 11990104
TI  - Putative cardiotoxicity of the venoms of three mamba species.
AB  - The venoms of all mamba species are known to contain potent neurotoxins. Some
      authors suggest that cardiotoxins from mamba venom are responsible for heart
      failure in envenomated patients. This study was undertaken to come to a better
      understanding of the mechanisms and possible effects of mamba venom on the hearts
      of animals. The venoms of three mamba species namely Dendroaspis polylepis,
      Dendroaspis angusticeps, and Dendroaspis jamesoni were screened for
      cardiotoxicity by the cardiomyocyte viability test on cardiomyocytes isolated
      enzymatically from guinea pig ventricle muscle. This analysis was followed by an
      electrophysiological evaluation of the effects of venoms (from the Dendroaspis
      species) on cardiac ion channels by employing the whole-cell clamp procedure. In
      this study the cardiomyocyte viability test indicates differences among the
      venoms of the three mamba species. The venom of D. jamesoni seems to be the most
      potent followed by D. angusticeps and then D. polylepis. The whole-cell clamp
      results indicate that the venoms have no affinity for cardiac potassium channels
      but have an inhibitory influence on cardiac L-calcium channels. Although this
      study provides evidence that mamba venoms have a specific effect on isolated
      myocytes of guinea pig, it is doubtful that it will have a profound influence on
      a human heart in case of envenomation.

PMID- 11990105
TI  - Inaccuracy of three-finger pinch method of determining salt content in homemade
      sugar salt solutions.
AB  - Oral rehydration therapy (ORT) has dramatically reduced the morbidity and
      mortality associated with acute infectious diarrhea. Commercial oral rehydration
      salt (ORS) solutions with sodium concentrations of 30-90 mmol/L are ideal for
      both the prevention and treatment of dehydration. However, logistic issues impede
      their universal availability and homemade sugar salt (HSS) solutions are widely
      used in some areas of the world. The least accurate methods of preparing HSS
      solutions utilize a three-finger pinch of salt. The present study demonstrates
      the inconsistency and inaccuracy of this method among 15 health workers who
      participated in an ORT training seminar conducted in a situation that
      approximated field conditions. Similar studies with different subjects,
      instructions, and milieu describe results similar to those we obtained. In all
      studies, including the present one, a substantial number of the solutions
      prepared by this method had dangerously high or low sodium concentrations. Health
      providers should consider the use of selected home-available fluids rather than
      HSS solutions for the prevention of dehydration in children with diarrhea.
      However, ORS solutions should be used to correct established dehydration.

PMID- 11990106
TI  - Treatment of high-altitude pulmonary edema by bed rest and supplemental oxygen.
AB  - STUDY OBJECTIVES: We evaluated the safety and efficacy of treating high-altitude
      pulmonary edema (HAPE) by bed rest and supplemental oxygen at moderate altitudes.
      We also characterized clinical parameters in HAPE before and after treatment.
      DESIGN: Case series. SETTING: Two primary care centers at about 9,200 feet (2,800
      meters) above sea level. TYPE OF PARTICIPANTS: All patients aged 16-69 years who
      had been diagnosed with HAPE and were treated with bed rest and supplemental
      oxygen. Patients were seen on a follow-up visit. INTERVENTIONS: Selected patients
      were treated with bed rest and supplemental oxygen rather than hospital admission
      or descent. MAIN OUTCOME MEASURE: Patients were considered improved on follow-up
      if room air arterial oxygen saturation was increased by 10 percentage points or
      if their symptoms had improved. RESULTS: Of 58 patients with confirmed HAPE, 25
      (43%) were treated by bed rest and supplemental oxygen and were seen on return
      visits to the clinic. All of the treated patients improved at the return visit.
      Systolic blood pressure, heart rate, respiratory rate, and temperature decreased
      significantly between the first visit and the return visit. Oxygen saturation
      improved between visits. CONCLUSION: Some patients with HAPE at moderate
      altitudes where medical facilities are available can be safely treated with bed
      rest and oxygen without descent.

PMID- 11990107
TI  - Biology and treatment of the mamba snakebite.
AB  - Mambas are venomous African snakes that are capable of inflicting fatal
      envenomation. The mambas (genus Dendrosaspis) are members of the family Elapidae
      [1]. Four species of mamba inhabit equatorial and southern Africa. Without
      medical treatment, mamba bites are frequently fatal. First aid treatment includes
      lymphatic retardation with immobilization and pressure wrap. Medical management
      requires the intravenous administration of mamba-specific antivenin.

PMID- 11990108
TI  - Wilderness dermatology: prevention, diagnosis, and treatment of skin disease
      related to the great outdoors.

PMID- 11990109
TI  - Case report of a coyote attack in Yellowstone National Park.
AB  - We report the case of an unprovoked coyote attack on a human visitor to
      Yellowstone National Park. Although the patient suffered only soft tissue
      injuries, unprovoked attacks are rarely reported in the medical literature. This
      case and plans on how to manage coyote attacks are discussed.

PMID- 11990110
TI  - Aircraft down.

PMID- 11990111
TI  - Attempted isolation of Blastomyces dermatitidis from rectal cultures of beaver
      (Castor canadensis) from north central Wisconsin.

PMID- 11990112
TI  - Enalapril in the treatment of chronic mountain sickness.

PMID- 11990113
TI  - Medical aid to developing countries.

PMID- 11990114
TI  - Physiological effects of downhill skiing at moderate altitude in untrained middle
      aged men.
AB  - To evaluate whether occasional strong physical activity at moderate altitude for
      several consecutive days is acceptable in untrained middle-aged people, 10 men
      (age range, 46-59 years) underwent physical examinations before (control day,
      D0), during (D1-D8), and after 1 wk of leisure alpine skiing. With respect to D0,
      the resting concentration of plasma noradrenaline (NOR) increased transiently (p
      < 0.01) on D2 and then increased to a maximal value from D6-D8 (p < 0.01). There
      was no significant change in the concentration of adrenaline. Although maximal
      voluntary contraction of knee extensors diminished on D3 (P < 0.05), that of the
      digit flexors did not change. Heart rate (HR) and blood pressure at rest in the
      evening were always higher than control values except on D4 (forced rest). After
      the stay, there was a reduction in sympathetic activity. This was reflected by a
      return of NOR to its control value, a decrease in resting HR (64.2 [11.4] beats
      per minute [bpm]: control: 71.1 [10.1] bpm, P < 0.02), a tendency for
      triglyceride and insulin resistance to decrease, and a significant increase in
      alipoprotein A1/alipoprotein A2 (P < 0.01). Our results show that despite signs
      of fatigue on D3, the effects of physical activity that is relatively intense (HR
      > 70% maximal HR) together with mild hypoxia are well tolerated by untrained
      middle-aged men and that the controlled practice of downhill skiing may be
      accepted into a program to lower cardiovascular risk factors.

PMID- 11990115
TI  - Advanced life support in the wilderness: 5-year experience of the Reach and Treat
      team.
AB  - Increasing recreation in the wilderness raises questions about the value of
      providing advanced life support (ALS) care in the backcountry. Since 1989 the
      Reach and Treat (RAT) team has provided ALS care in the wilderness area that
      surrounds Mount Hood, Oregon. The purpose of our study was to describe patient
      demographics, terrain, injuries, and ALS treatment in the wilderness environment.
      We utilized a retrospective, observational analysis of RAT missions from 1989 to
      1994 based on data sheets maintained by the RAT team, prehospital run sheets, and
      hospital charts. Of the 114 missions analyzed, the median time of missions was 3
      h, 9 min (range, 44 min-76 h) and 20% required technical climbing skills. Of the
      74 patients treated, 55 (90%) received ALS care: 8 were intubated, 52 had
      intravenous lines established, and 24 received morphine for pain. Twenty patients
      were entered into the local trauma system. The most common injuries were
      extremity injuries (58), head injuries (18), and hypothermia (15). Mean time from
      arrival to return to staging area was 95 min. No injuries to RAT team members
      occurred during these missions, although two minor injuries occurred during
      training and testing. We found that wilderness-trained paramedics safely provided
      ALS care in a backcountry environment. This care may improve patient comfort
      during long extrication and speeds the arrival of potentially life-saving
      interventions such as advanced airway management.

PMID- 11990116
TI  - Elevation of serum cholesterol at high altitude and its relationship to
      hematocrit.
AB  - The positive relationship between hematocrit and serum cholesterol may be due to
      dilution. Accordingly, high hematocrits would yield reduced serum pools for
      dilution of cholesterol, thus producing higher levels. To test this effect, the
      relationships between hematocrit and cholesterol were evaluated at low-altitude
      and high-altitude clinics. Retrospective chart reviews were conducted at Madison,
      WI (264 m) and Leadville, CO (3105 m) to identify family practice patients who
      underwent hematocrit and serum cholesterol determinations on the same day. We
      excluded patients with medical conditions or on medications that affect
      cholesterol, patients with high glucose and triglyceride levels, and patients
      with extreme cholesterol levels. Remaining patients (153 in each altitude group)
      were matched by age and sex. The mean hematocrits and cholesterol levels were
      compared using analysis of variance. The linear relationships between hematocrit
      and cholesterol were compared using analysis of covariance. The mean hematocrit
      was significantly higher at high altitude (47.5% versus 41.3%; p < 0.0005) as
      were the mean serum cholesterol (190 mg/dL versus 177 mg/dL; p < 0.002) and the
      low-density lipoprotein:high-density lipoprotein ratio (2.80 versus 2.27; p <
      0.05). Whereas a significant, positive relationship existed between hematocrit
      and cholesterol at low altitude (2.15 mg/dL per %; p < 0.002), no such
      relationship was found at high altitude. Hematocrit and serum cholesterol were
      elevated for family practice patients living at high altitudes. Differences exist
      between altitudes in the relationship between hematocrit and cholesterol.
      Acclimatization to high altitude and its resultant erythropoiesis may increase
      serum cholesterol levels. Consequently, relocation to a high altitude may
      increase the risk of arteriosclerotic cardiovascular disease.

PMID- 11990117
TI  - Backcountry snowboarding: medical and safety aspects.
AB  - As backcountry snowboarding becomes increasingly popular, wilderness enthusiasts
      and medical providers should be aware of its medical and safety aspects. This
      overview highlights the history of snowboarding and snowboarding today. In
      addition to proper mountaineering gear and winter clothing, special equipment is
      needed including a backpack, boots, a snowboard, and a method of ascent such as
      snowshoes. Medical studies on resort snowboarding have been reviewed and related
      to the wilderness setting for this study. Special limitations pertaining to
      snowboards are also discussed. For safety, one should seek instruction, practice,
      and experience in all aspects of backcountry travel including weather reading,
      route finding, enviromental hazards, cold injury treatment, and construction of
      emergency bivouacs. Backcountry snowboarders should be experts or at least
      advanced intermediates and should be proficient at climbing, snowshoeing, or free
      heel skiing for ascent. One should understand avalanche terrain and glacier
      travel and he prepared for rescue. Snowboarders should also take limitations of
      snowboards into consideration when riding in the backcountry.

PMID- 11990118
TI  - Drug-induced hypoglycemia presenting as acute mountain sickness, after mistaking
      acetohexamide for acetazolamide.
AB  - Acute mountain sickness (AMS) can present with a wide variety of symptoms in
      unacclimatized persons who rapidly ascend to altitudes > 2500 m. The clinical
      manifestations of drug-induced hypoglycemia, including adrenergic and neurologic
      symptoms, have significant overlap with the AMS symptom complex. These
      similarities can lead to confusion in the diagnosis of hypoglycemia versus AMS,
      particularly for diabetics ascending to altitude. A case is described in which
      the oral hypoglycemic agent acetohexamide, instead of acetazolamide, was
      mistakenly self-administered for the prophylaxis and treatment of altitude
      illness. Improper self-medication by travelers in remote areas may be more common
      than is currently recognized.

PMID- 11990119
TI  - A Bushmaster bite during a birding expedition in lowland southeastern Peru.
AB  - Birders and other ecotourists are traveling to increasingly remote areas of the
      world where sophisticated medical care may be difficult to obtain. This report
      presents a case of a Bushmaster (Lachesis muta muta) bite in Peru and details the
      difficulties encountered from initial care to evacuation and definitive medical
      care.

PMID- 11990120
TI  - The hug.

PMID- 11990121
TI  - Hiking sticks in mountaineering.

PMID- 11990122
TI  - Safety at extreme altitudes: the 1995 American North Ridge Everest Expedition.

PMID- 11990123
TI  - Wilderness as medicine for the disabled.

PMID- 11990124
TI  - What price a summit?

PMID- 11990125
TI  - The Environmental Council of the WMS. Wilderness Medical Society.

PMID- 11990126
TI  - Lionfish envenomations in an urban wilderness.
AB  - Marine envenomations are commonly encountered along coastal regions of the United
      States. Although less frequent, marine bites and stings do occur in landlocked
      locales, such as the Midwest, because of an increased interest in keeping these
      exotic creatures as pets. We report 33 cases of envenomations by captive lionfish
      (Pterois volitans) called to a regional Chicago poison control center over a 2
      year period. All stings were accidental, and 10 (30%) were treated in an
      emergency department. The wounds were uniformly on the hand, and all presented
      with local, intense pain. The majority of envenomations were responsive to prompt
      immersion in nonscalding water within 90 min, and all were advised on tetanus
      prophylaxis and local wound care. Two patients (6%) required hospitalization. In
      all cases, those patients envenomated recovered without permanent sequelae. As a
      result of increasing encounters with lionfish as pets, health care providers.
      regardless of their locale, should be familiar with the current treatment
      recommendations.

PMID- 11990127
TI  - Bites by non-native venomous snakes in the United States.
AB  - Fifty-four consultations regarding bites by venomous snakes not native to the
      United States are summarized. These are from a database of 164 consultations
      during the period 1977- 1995. At least 29 non-native snake species were involved
      with cobras making up -40% of the group. There was one fatality. A high
      percentage of venomous snakebites in the United States involve deliberate
      interaction with snakes. The proportion of bites by non-native species seems to
      be increasing. Some of the snake species involved are discussed, and some
      principles for management of these bites are given.

PMID- 11990128
TI  - Asthma exacerbations during Santa Ana winds in southern California.
AB  - This study investigated the relationship between Santa Ana wind conditions and
      visits for asthma at a southern California emergency department. Visits to the
      emergency department for asthma were analyzed retrospectively to determine
      whether the incidence increased during Santa Ana wind conditions. These
      northeasterly winds are common during fall and winter in southern California and
      belong to a class known as Foehn winds. They are characterized by gusty winds,
      decreased relative humidity, warm temperatures, and decreased levels of airborne
      pollutants. During a 4-year period, we noted that emergency department visits for
      asthma increased (3.12 vs. 2.16 visits per day, P < 0.0001) during SantaAna winds
      compared with other weather conditions. Asthmatics presenting during Santa Ana
      winds appeared to be more ill, as judged by higher admission rates (21.9 vs.
      18.7%, P < 0.05). These winds were also associated with reduced particulate
      matter (PM10) counts (P < 0.0001). Although the magnitude of the increase in
      emergency department visits was small, it occurred at a time when typical
      inciters of respiratory disease should be minimal. An as yet unidentified factor
      associated with these winds may be a stimulant for some asthmatics. Similar wind
      patterns in other localities might affect respiratory disease as well.

PMID- 11990130
TI  - Writing about medicine.

PMID- 11990129
TI  - Experimental approaches to therapy and prophylaxis for heat stress and
      heatstroke.
AB  - New developments in the fields of biochemistry, physiology, sepsis, cancer
      therapy, and molecular genetics have led to opportunities for the development of
      new therapies and prophylaxes for heat illnesses and for improving human
      performance during conditions of environmental stress. These include
      antilipopolysaccharide agents, anticytokines, potassium channel agents, a diet
      rich in omega-3 fatty acids, and psychological conditioning. This review
      summarizes the backgrounds and recent findings in the above fields and provides
      specific suggestions for potential therapy and prophylaxis for classic and
      exertional heatstroke and for improving athletic performance.

PMID- 11990131
TI  - The use of pegorgotein in the treatment of frostbite.
AB  - Free oxygen radicals have been postulated to be an important mediator of injury
      in frostbite. A long-acting version of the endogenous scavenger enzyme,
      superoxide dismutase, has been created by conjugating it with polyethylene glycol
      (pegorgotein, formerly known as PEG-SOD). This study evaluated the efficacy of
      pegorgotein on frostbite tissue survival when administered prior to rewarming. In
      a prospective study, two groups of nine rabbits received a standardized frostbite
      injury using a modified Weatherley-White model. A control group received no
      pharmacologic therapy; the treatment group received 10,000 IU/kg pegorgotein
      intravenously immediately postinjury. Healing was followed until a clear line of
      demarcation was apparent (10 days). The percentage of viable ear surface
      remaining at the end of the study was measured and used to compare the
      effectiveness of treatment. Student's t-test was used to determine statistical
      significance. The study was designed to have an 80% ability to detect a 35%
      difference in tissue survival. No significant difference in frostbite injury (p =
      0.967) was observed between the control and treatment groups. The treatment group
      showed a 9.3 +/- 15.5% tissue survival, whereas the control group had 9.6 +/-
      14.5% tissue survival. These results indicate no significant treatment effect for
      pegorgotein on tissue survival in a rabbit frostbite injury model when
      administered immediately postinjury.

PMID- 11990132
TI  - Management of thai cobra bites with a single bolus of antivenin.
AB  - Between January 1981 and December 1991, 68 adults were treated at Chulalongkorn
      University for cobra bites. Respiratory failure developed in the bite victims
      even when an adequate genus-specific antivenin was administered at the onset of
      neuromuscular paralysis. The duration of time spent on a respirator was, however,
      significantly less in patients treated with an intravenous 100-ml antivenin bolus
      given at the onset of neurotoxic signs. We found that a bolus of 100 ml of
      purified equine antivenin produced by the Queen Saovabha Memorial Institute,
      Bangkok, from Naja kauthia venom was adequate and that increasing the dose did
      not lead to added benefits. Time spent on a respirator was approximately 10 h in
      antivenin-treated groups and 40 h if no antivenin or an inadequate dose was used.
      Competent respiratory and nursing care alone without antivenin will lead to
      eventual recovery and prevent death. Local bite site tissue necrosis and duration
      of hospitalization were not related to the dose of antivenin given.
      Hospitalization was prolonged in subjects who developed sepsis or who had severe
      tissue necrosis or other surgical or medical complications.

PMID- 11990133
TI  - Stingray injuries.
AB  - Stingray injuries to humans are common in warm coastal areas. Wounds have a
      traumatic (puncture) component and a toxic (envenomation) component. The puncture
      component is like a stiletto-type knife wound, most often inflicted on the lower
      leg (waders) or arm (fishermen). Rare puncture injuries to the thorax or abdomen
      can cause serious injuries and death. Envenomation causes intense pain that is
      out of proportion to the apparent injury. The pain of stingray envenomation is
      relieved with hot-water immersion of the injured part, although the exact
      mechanism for this well-established phenomenon remains unclear. Current
      recommendations for treating stingray wounds are reviewed.

PMID- 11990134
TI  - Everest 1951: the footprints attributed to the Yeti--myth and reality.
AB  - For centuries, mountains have given rise to legends about supernatural beings
      such as the Yeti of the Himalayas. The legend of the Yeti was enhanced by the
      finding of footprints in the Menlung Basin during the 1951 Everest reconnaissance
      expedition. This report provides a possible explanation of the Menlung footprints
      based on developmental abnormalities, physiology, and pathology of the foot.

PMID- 11990135
TI  - Does shivering thermogenesis enhance the individual's ability to maintain rectal
      temperature during immersion in cold water?
AB  - Shivering thermogenesis may enable individuals to maintain rectal temperature
      during acute cold exposure. This data analysis revisited this hypothesis and
      compared previously published data with unpublished data from our laboratory on
      those subjects that were terminated from cold water immersion early because of a
      reduction in rectal temperature (T(re)) - 35 degrees C. T(re), mean skin
      temperature (T(sk)), and oxygen uptake (VO2) were recorded at 5, 30, 60, and 90
      min of immersion and were used to calculate 3delta readings for each exposure,
      that is, deltaT(30) minus T5, T60 minus T(30), and T(90) minus T(60). Single
      group t-tests were used to examine differences in deltaT(re), deltaT(sk), and
      deltaVO2 between the published data (PD) group and the individual subjects who
      were terminated early (TE) at each of three water temperatures (18 degrees C, 22
      degrees C, 26 degrees C). For deltaVO2 the TE subjects were dichotomized by
      fatness (low percent fat, 8%-12%; or high percent fat, 18%-22%) to account for
      the VO2 differences between these groups (i.e., fatness) during cold water
      immersion. deltaT(re) was significantly (p < 0.05) decreased in TE subjects
      compared with PD subjects at all timepoints for 18 degrees C and 26 degrees C. At
      22 degrees C, the TE subject exhibited a significantly greater (p < 0.05)
      decrease in deltaT(re) than the PD group at 90 min of immersion only. No
      significant (p > 0.05) differences in deltaT(sk) between the PD and TE groups
      were detected for any of the exposure temperatures over all time points. No
      difference (p > 0.05) between PD subjects and TE subjects for deltaVO2 was
      exhibited at any time point at any temperature. It appears that with respect to
      the TE group, elevations in VO2 were comparable to the PD group, but the TE group
      was unable to maintain T(re) during cold water immersion. In conclusion, from
      these data it appears that shivering thermogenesis does in part enhance the
      individual's ability to maintain T(re); however, as evidenced in the TE group, it
      also appears that the alterations in shivering thermogenesis for certain
      individuals may not be great enough to offset heat loss.

PMID- 11990136
TI  - Outward bound on Kilimanjaro.

PMID- 11990137
TI  - Reference texts for medical practice in remote and tropical settings.

PMID- 11990138
TI  - Let the buyer beware.

PMID- 11990139
TI  - Deaths resulting from animal attacks in the United States.
AB  - The objective of this study was to elucidate the etiology and frequency of deaths
      in the United States from encounters with animals. The number of deaths from
      venomous and nonvenomous animals is reported annually to the US Department of
      Health and Human Services and published in Vital Statistics of the United States.
      This study is a survey of all animal-related fatalities listed as E-codes 905-906
      reported in the Vital Statistics of the United States from 1979 through 1990.
      Data were extracted uniformly from the annual reports and analyzed using
      descriptive statistics. From 1979 through 1990, there were 1882 animal-related
      deaths in the United States. Venomous animals caused 718 deaths; nonvenomous
      animals caused 1164 deaths. Most deaths occurred among white males. The home site
      was the location of injury for the majority of deaths. The majority of venomous
      animal-related deaths were from hymenoptera; "other specified animal" caused the
      majority of nonvenomous deaths. An annual average of 157 deaths from animal
      attacks occurred in the United States between 1979 and 1990. Both fatal and
      nonfatal animal-related injuries are under-recognized public health hazards.
      Health care providers should educate their patients on exercising caution around
      animals, seeking medical care after an animal injury, carrying epinephrine kits
      if they have a history of systemic reactions to insect stings, and wearing
      helmets and other protective equipment when riding or working around large
      animals.

PMID- 11990140
TI  - GPS signal reception under snow cover: a pilot study establishing the potential
      usefulness of GPS in avalanche search and rescue operations.
AB  - Avalanches are one of the major threats to life in high-mountain terrain and
      account every year for approximately 150 accidents causing injury or death in the
      United States alone. Every year avalanches cause significant property damages and
      a death toll of approximately 15 people in the United States. The specific
      characteristic of the avalanche accident is the extreme importance of getting to
      the buried victim as soon as, possible to improve survival. Approximately 40% of
      all buried victims survive 1 hour, and only about 20% survive 2 hours. Newer
      studies from Europe indicate that the initial survival probability is 92% at 15
      minutes, 30% at 35 minutes, 27% at 90 minutes, and finally drops to 3% at 130
      minutes. Unless prompt and efficient search and rescue are ensured, the prospect
      of buried victims is rather grim. Many tools have been used in the past to aid in
      retrieving buried victims including the avalanche cord, probing techniques, and
      in more recent time, the use of electronic beacon devices that allow search teams
      to locate the buried victim. The advent of satellite navigational aids (GPS,
      GLONASS) makes it possible to determine one's position with remarkable accuracy.
      We studied the degree to which the GPS satellite signal could penetrate through
      snow and be received by a commercially available GPS receiver. This information
      may lead to the development of an additional tool for precise and quick
      localization of buried victims in avalanche accidents and thus may substantially
      improve their survival by shortening the search time at the accident site. In
      this study we used a Motorola Traxar six-channel GPS receiver with amplifier unit
      connected to an antenna by means of a shielded coaxial cable. The antenna was
      buried under incremental covers of compact snow, and the reception of the GPS
      signal was measured at each burial depth: 5 cm, 15 cm, 25 cm, 35 cm, 45 cm, 55
      cm, 1 m, and 1.5 m. The variables that were measured included signal quality,
      number of satellites received by the receiver, and their respective signal
      strength. A reference reading was taken from the GPS receiver above the testing
      site before measurements under snow cover were started. The satellite signals
      were received with good quality and precise readings up to a burial depth of 1 m.
      Under 1.5 m of snow the receiver was able to lock on only one satellite, making a
      positional reading impossible. The reception of the GPS signals under snow cover
      is possible and warrants further study directed toward the development of a
      search and rescue device using this technology.

PMID- 11990141
TI  - On the trail of potassium in heat injury.
AB  - In both classical and exertional heatstroke and in various animal models of human
      heat injury, clinical manifestations have included observations of normokalemia,
      hyperkalemia, and hypokalemia. This review attempts to address these observations
      as well as the role of potassium and potassium depletion in heat injury with an
      emphasis on the integration of information from the level of transmembrane
      potassium transport mechanisms to systems physiology. Under moderate conditions
      of passive heat exposure or exercise in the heat, the adaptive capacity of the Na
      K pump (Na+-K+ ATPase activity) and cotransport mechanisms can ordinarily
      accommodate the attendant increased efflux of intracellular K+ and influx of
      extracellular Na+ to maintain ionic equilibrium. Several factors affecting
      transmembrane K+ kinetics include protracted K+ deficiency, extreme hyperthermia,
      dehydration, and excessive exertion. These could elicit reduced membrane
      potentials and conductance, futile cycling of the Na-K pump with concomitant
      energy depletion and greatly increased metabolic heat production, reduced
      arteriolar vasodilation, altered neurotransmitter release, or cell swelling, each
      of which could contribute to the pathophysiology of heat injury. This review
      represents a preliminary attempt to link transmembrane K+ pathophysiology with
      clinical heat injury.

PMID- 11990142
TI  - Report on envenomation by a Gila monster (Heloderma suspectum) with a discussion
      of venom apparatus, clinical findings, and treatment.
AB  - Human envenomations by Heloderma species are a rare but clinically important
      medical problem. We report a case of an adult male bitten on the left hand by a
      50-cm male, captive specimen of Heloderma suspectum (Gila monster). Immediate
      signs and symptoms included pain at the bite site radiating into the arm and
      axilla and swelling of the hand and forearm. Systemic complaints of nausea,
      diaphoresis, and dizziness (without a decrease in blood pressure) lasted
      approximately 1 hour, and laboratory studies were normal. The patient's course
      was uneventful except for persistent hyperesthesia, which eventually abated. Two
      types of helodermatid bites produce distinct clinical pictures. The chewing bite
      potentially causes more envenomation than the slashing bite. The venom contains a
      number of protein and nonprotein components including serotonin, a bradykinin
      releasing substance, protease, hyaluronidase, helodermin, and gilatoxin. The
      clinical presentation of a helodermatid bite can include pain, edema,
      hypotension, nausea, vomiting, weakness, and diaphoresis. No antivenin is
      commercially available. Treatment is supportive, and although first aid measures
      such as suction or compression may impede venom movement, they are unproved.
      Cryotherapy, tourniquet, and excision are dangerous and should not be used.

PMID- 11990143
TI  - The power of scenario.
AB  - Teaching wilderness medicine to medical students comes alive when nontraditional
      methods are used. In our wilderness medicine elective at the University of
      Massachusetts Medical School, the teaching is primarily experientially based. The
      following anecdote illustrates the magic that can happen when teaching is done
      via the scenario-debriefing method.

PMID- 11990144
TI  - Tourism and the health of local populations.

PMID- 11990145
TI  - Water disinfection strategies for Cryptosporidium.

PMID- 11990146
TI  - Medical problems of porters and trekkers in the Nepal Himalaya.
AB  - The purpose of this study was to assess the incidence of medical illness among
      members of trekking groups in the Nepal Himalaya. The design was a cohort study
      using interview and clinical examination by a single physician. The setting was
      the Manaslu area in the central Nepal Himalaya along a 22-day trekking route with
      elevations ranging from 487 m to 5100 m. Subjects were 155 members of commercial
      trekking groups: 102 Nepali porters, 31 Nepali trek staff, and 22 Western
      trekkers. We found that medical problems occurred in 45% of party members. The
      porter cohort contained the highest diversity and severity of illness. The
      relatively larger porter cohort experienced 77% of the medical problems recorded
      compared with 17% among Western trekkers and 6% among trek staff. The incidence
      of medical problems was not significantly different in the porter staff (52%) and
      Western trekkers (55%) and was significantly lower for the trek staff (13%). High
      altitude pharyngitis/bronchitis was the most common illness in the party (12%)
      followed by acute mountain sickness (8%) and gastroenteritis (6%). Other
      conditions included anxiety (3%), cellulitis (3%), scabies (3%), snow blindness
      (3%), acute alcohol intoxication (2%), conjunctivitis (2%), fever (2%),
      lacerations (2%), and hemorrhoids (1%). Illness with infectious etiologies
      comprised 33% of the medical problems. The incidence of altitude illness was not
      significantly less in the Nepali porter staff than in the Western trekkers.
      Evacuation was required in 5% of party members, all from the porter group. This
      study should alert expedition medical providers and trip leaders of the need to
      be observant for and prepared to treat the frequent and diverse medical problems
      among the porter staff in their party, in addition to the Western members.
      Medical problems are common in remote mountainous areas, indicating that trip
      physicians should be experienced in primary care.

PMID- 11990147
TI  - Injury and illness in a wilderness multisport endurance event.
AB  - Our objective was to identify patterns of injury and illness and develop possible
      preventive strategies for competitors in a wilderness multisport endurance event.
      Using a prospective observational cohort study during the Winter Classic, a 2-day
      wilderness multisport endurance event held in rugged alpine terrain in Victoria,
      Australia, we sought details of demographics, pre-, intra-, and postrace injuries
      and illness. We employed chi-squared tests and iterative multivariate analysis.
      There were 33 respondents with 26 (78%) aged between 26 and 35 years. Seven (21%)
      developed symptoms consistent with exposure, and three (9%) developed asthma
      during the race. Competitors in the marathon pairs class had a 50% risk of
      exposure vs 12% for the individual class (p = 0.031). The number of times raced,
      nonsteroidal anti-inflammatory drug use, and increasing age were the other
      independent significant predictors of exposure. Twenty-three (70%) of the
      competitors were injured at some time during the race. The day 1 run was more
      commonly associated with injuries than other stages (39% injured, p = 0.0037).
      Increased amounts of training, previous musculoskeletal problems, and increased
      number of previous race attempts were all significant independent predictors of
      injury. Most competitors (67%) suffered musculoskeletal problems after the race,
      these typically being of the thighs and calves, but only two competitors required
      time off from their normal activities. We concluded that injuries in wilderness
      multisport endurance events are common, particularly in the run stages. These
      injuries are usually minor, but their frequency makes major injury an ever
      present risk. Both injury and illness are more frequent in those who compete
      while carrying injuries. These events are high risk for the development of
      injuries and illness and require a high level of competitor preparation and
      readily available medical support.

PMID- 11990148
TI  - Mojave rattlesnake envenomation in southern California: a review of suspected
      cases.
AB  - To clarify whether Mojave rattlesnake (Crotalus scutulatus scutulatus)
      envenomations occurring in California cause typical crotalid tissue effects,
      pain, edema, and ecchymosis, we reviewed charts of snakebite victims at a
      tertiary care teaching hospital and a moderate-size community hospital. Forty-two
      patients were bitten within the range of Mojave rattlesnakes. Eight snakes were
      identified as Mojave rattlesnakes (group 1); of these, four were confirmed by
      experts in snake identification (group 1a). Fifteen patients were reported bitten
      by other rattlesnake species (group 2), and in 19 envenomations the species was
      unknown (group 3). Seventy-five percent of patients in group 1 were reported to
      have local edema at the envenomation site compared with all of the patients in
      group 2. Ecchymosis was found in 25% of group 1 patients and 73% of group 2
      patients. Pain was documented in only 12% of group 1 and 67% of group 2 victims.
      Neurotropic events, many severe, were found in 75% of group 1 patients compared
      with 7% of those in group 2. Although this study does not have the power to
      justify statistical evaluation, C. scutulatus envenomations do appear inclined to
      less tissue reaction. A disturbing trend toward severe neurotropic manifestations
      was also suggested in presumed Mojave rattlesnake envenomations.

PMID- 11990149
TI  - Red snow: is it safe to eat? A pilot study.
AB  - The objective of this study was to determine if the ingestion of snow
      contaminated with Chlamydomonas nivalis causes diarrhea. The design was a single
      blind crossover. Subjects were seven healthy volunteers, aged 24-56 who ingested
      500 g of snow contaminated with C. nivalis. Outcome was measured by stool and
      diarrhea frequency. No differences in stool or diarrhea frequency were noted
      between treatment and placebo groups. The conclusion is that in this pilot study,
      there was no evidence supporting the concern that ingestion of "red snow" causes
      diarrhea.

PMID- 11990150
TI  - Efficacy of iodine water purification tablets against Cryptosporidium oocysts and
      Giardia cysts.
AB  - The ability to control water-borne diseases is critical for soldiers, hikers, and
      others who may need to drink directly from an outdoor source. Water-borne
      protozoan parasites that are specifically of concern are Giardia and
      Cryptosporidium because of their resistance to halogen disinfection. The purpose
      of this study was to determine the effectiveness of iodine tablets against
      Giardia and Cryptosporidium under general- and worst-case water conditions that
      might be found in the field. Giardia cysts and Cryptosporidium oocysts were
      exposed to iodine according to manufacturer's instructions (two tablets/L = 13-18
      mg/L for 20 minutes). This dose inactivated 3-log10 of Giardia in general-case
      water and pH 9. In worst-case water, however, only about 35% of cysts were
      inactivated at pH 5. Fifty minutes were required to achieve a 3-log10 reduction
      at pH 5. Cryptosporidium oocysts were more difficult to inactivate. Only 10% were
      inactivated after a 20-minute exposure to iodine according to manufacturer's
      instructions; even after 240 minutes of exposure to iodine only 66-81% oocysts
      were inactivated. These data strongly suggest that iodine disinfection is not
      effective in inactivating Cryptosporidium oocysts in water. Because this organism
      is common in all surface waters, it is recommended that another method of
      treatment be used before ingestion.

PMID- 11990151
TI  - Paragliding accidents in remote areas.
AB  - Paragliding is an increasingly popular hobby, as people try to find new and more
      adventurous activities. However, there is an increased and inherent danger with
      this sport. For this reason, as well as the inexperience of many operators,
      injuries occur frequently. This retrospective study centers on the helicopter
      rescue of 70 individuals in paragliding accidents. All histories were examined,
      and 43 patients answered a questionnaire. Nineteen (42%) pilots were injured when
      taking off, 20 (44%) during the flight, and six (13%) when landing. Routine and
      experience did not affect the prevalence of accident. Analysis of the causes of
      accident revealed pilot errors in all but three cases. In 34 rescue operations a
      landing of the helicopter near the site of the accident was possible. Half of the
      patients had to be rescued by a cable winch or a long rope fixed to the
      helicopter. Seven (10%) of the pilots suffered multiple trauma, 38 (54%) had
      injuries of the lower extremities, and 32 (84%) of them sustained fractures.
      Injuries to the spine were diagnosed in 34 cases with a fracture rate of 85%. One
      patient had an incomplete paraplegia. Injuries to the head occurred in 17
      patients. No paraglider pilot died. The average hospitalization was 22 days, and
      average time of working inability was 14 weeks. Fourteen (34%) patients suffered
      from a permanent damage to their nerves or joints. Forty-three percent of the
      paragliders continued their sport despite the accident; two of them had another
      accident. An improved training program is necessary to lower the incidence of
      paragliding accidents. Optimal equipment to reduce injuries in case of accidents
      is mandatory. The helicopter emergency physician must perform a careful
      examination, provide stabilization of airways and circulation, give analgesics,
      splint fractured extremities, and transport the victim on a vacuum mattress to
      the appropriate hospital.

PMID- 11990152
TI  - Does capsaicin affect the thermal sensation of males during immersion in 18
      degrees C and 22 degrees C?
AB  - Animals respond to acute local or systemic administration of capsaicin with
      strong nociceptive reactions. The present investigation examined the thermal
      sensation in males who were given capsaicin (CAP, 2 mg x kg(-1) body weight) vs a
      placebo (PL, a maltodextrin capsule) before immersion in cold water. Seven
      Caucasian males ages 20-28 years were immersed in 18 degrees C and 22 degrees C
      twice (PL vs CAP) for 120 minutes. The following were examined: metabolism (VO2;
      L x min(-1)), rectal temperature (Tre; degrees C), and thermal sensation (TS).
      For VO2 there were no significant differences between treatments (PL vs CAP) when
      the variables were pooled jointly over the two immersion temperatures (18 degrees
      C and 22 degrees C) and across time. However, for Tre there were significant
      differences detected across time (p = 0.01) when Tre was pooled jointly across
      two treatments and two immersion temperatures. Postanalysis of variance revealed
      specific significant differences between 5 minutes (mean +/- SE; 37.2 +/- 0.07)
      and 120 minutes (36.0 +/- 0.09). For TS, there was a trend (p = 0.0699) which
      demonstrated differences between immersion temperatures only when TS was pooled
      jointly over the two treatments and across time, whereby TS was lower in 18
      degrees C (6.2 +/- 0.5) than in 22 degrees C (3.7 +/- 0.6). From these data it
      appears that although Tre differed across time and temperature, respectively, a
      CAP feeding did not affect differentially the TS and metabolic response of males
      during acute cold water immersion.

PMID- 11990153
TI  - An analysis of the medical review process at the National Outdoor Leadership
      School.
AB  - A statistical analysis of the medical characteristics of students on field
      courses at the National Outdoor Leadership School (NOLS) was performed. This
      analysis determined that the group of students with the highest overall student
      scores (> or = 4 on a 1 through 5 scale) tended to score lower in the
      psychological counseling and current psychological treatment questions and scored
      significantly higher in the athletic ability question on the NOLS medical review
      form. This indicates that these individuals tended to have little or no history
      of counseling and psychological treatment and were more likely to be engaged in
      competitive sports. Discriminant analysis demonstrated that these variables also
      contributed the most to discerning mathematically among the four possible student
      outcome score groups, which ranged from the inability to complete a course
      (evacuation) through highly successful. Many of the questions on the current NOLS
      medical form could not be analyzed statistically because they demonstrated no
      variance among the groups. Although these questions may still be valuable for
      screening purposes, some of them could be reworded for increased sensitivity.
      Discriminant analysis of six responses on the medical form was 43.7% effective at
      classifying individuals to outcome groups, and it is likely that this could be
      more effective with some modifications to the evaluation process. Admissions
      personnel in outdoor programs are encouraged to include questions such as those
      mentioned above in their overall admission procedures and to examine them
      thoroughly in their admissions decisions. Although additional studies should be
      conducted to examine these issues more thoroughly, it is possible that
      programmatic changes would assist students without the above-mentioned
      characteristics in becoming more successful in field courses.

PMID- 11990154
TI  - Data-based selection of medical supplies for wilderness travel.
AB  - The objective of this study was to provide data-driven recommendations for the
      contents of a wilderness medical kit. Many similar recommendations in the current
      literature pertain to specialized pursuits or expeditions and are based solely on
      the opinions of the authors. By studying a relatively homogeneous group of 565
      participants in a summer trek program in the New York Adirondack State Park, we
      were able to analyze 3955 person-days of actual exposure. All incidents were
      coded by ICD-9 criteria, and actual utilization of first-aid supplies for these
      incidents was quantified. These supplies were supplemented by items recommended
      by current practice guidelines for treatment of the observed incidents. The
      findings were used to generate data-based recommendations for the contents of a
      first-aid kit which would be adequate to meet the needs of such groups, which
      probably resemble much of the wilderness use in the United States today.

PMID- 11990155
TI  - Snakebite injuries: contributing factors and intentionality of exposure.
AB  - The objective was to study the intent of exposure to snakes and other factors
      contributing to snakebite injuries in order to develop prevention strategies. We
      used a retrospective chart review and a follow-up telephone interview of
      snakebite victims who were admitted to a tertiary care center between 1985 and
      1994. The data collected included demographics, intent of exposure and host and
      environmental factors. I performed descriptive analysis. Twenty-four males and
      six females ranging in age from 2 to 93 years sustained bites from a variety of
      snakes including rattlesnakes, copperheads, and Egyptian cobra, and others. Sixty
      seven percent (20/30) of all bites resulted from intentional exposures to snakes:
      professional snake handlers (7), snake hunts (8), and playing with (aggravating)
      snakes in the wild (5). Sixty-five percent (13/20) of intentional exposures
      involved novices in a recreational/home setting, and 35% (7/20) occurred in an
      occupational setting. Unintentional exposures occurred while victims were walking
      in wooded areas, fishing by streams, gardening, and washing dishes indoors. Forty
      percent (12/30) of all victims had consumed alcohol before the snakebite, 92%
      (11/12) of whom were nonprofessionals with intentional exposures. Only eight
      victims (seven of whom were professional handlers) were using protective
      equipment. I concluded that the majority of snakebite injuries resulted from
      intentional exposures to snakes in which a variety of factors such as the use of
      alcohol and lack of protective equipment likely played a role.

PMID- 11990156
TI  - Cutaneous myiasis from Dermatobia hominis.
AB  - We present a case report of cutaneous myiasis in a foreign traveler who was
      infected by Dermatobia hominis while visiting South America. This patient
      developed a painful furuncular lesion on the anterior scalp and noted that the
      lesion drained a serosanguinous fluid for more than a month before definitive
      treatment. Invasion of mammalian tissue by the larval forms of D. hominis
      typically results in the formation of a classic furuncular lesion. For persons
      who present with a lesion that contains a central draining stoma located on an
      exposed body surface, the diagnosis of myiasis should always be considered. In
      addition to the case report, we present a discussion of furuncular myiasis and
      describe the peculiar life cycle of the human botfly. We also describe the
      various therapies that may be employed for treating cutaneous myiasis, including
      surgical extraction of the larva and asphyxiation of the larva by application of
      petroleum jelly or other fat derivatives to the central stoma or breathing
      aperture.

PMID- 11990157
TI  - Medical acupuncture enhances standard wilderness medical care: a case study from
      the Inca Trail, Machu Picchu, Peru, April 2, 1997.
AB  - This case report shows the integration of medical acupuncture into the standard
      medical care of a wilderness emergency situation. Despite conventional medical
      attention, a trekker suffering from an extremely painful conjunctivitis continued
      to suffer severe eye pain. The addition of medical acupuncture to his care
      resolved his eye pain promptly, enabling him to continue his trekking activities
      without further distress. Acupuncture has many potential applications to enhance
      the effects of standard medical care in wilderness and third world travel
      settings.

PMID- 11990158
TI  - Another patient with neck irradiation and increased susceptibility to acute
      mountain sickness.

PMID- 11990159
TI  - Fungal infection after excavation or natural disaster.

PMID- 11990160
TI  - Stingray bites.

PMID- 11990161
TI  - Tetrodotoxin poisoning and cardiac arrythmia.

PMID- 11990162
TI  - High-altitude pulmonary edema: more lessons from the master.

PMID- 11990163
TI  - Telemark skiing injuries: a three-year study.
AB  - Telemark skiing is an increasingly popular wilderness activity. Little is known,
      however, about the injuries incurred during modern telemark skiing. To determine
      the incidence and types of these injuries we carried out a prospective analysis
      of injured telemarkers over three ski seasons from November 1994 through May 1997
      at the Mount Hood Meadows ski area medical clinic in Oregon. Injured telemark
      skiers presenting to the clinic were asked to fill out a one-page survey, and a
      diagnosis was provided by the clinic physician or nurse. During the 1995-1996 and
      1996-1997 ski seasons, skiers were counted at the ski lifts to determine the
      proportion of telemark skiers, alpine skiers, and snowboarders using the lifts.
      Using these proportions and the total ticket sales for the year, the number of
      downhill skiers, snowboarders, and telemarkers over the season were estimated,
      and injury rates were calculated. During the three ski seasons, 33 injuries were
      identified in 28 injured telemarkers. Of the study participants, 75% (21) were
      male. The average age was 33.1 years. Self-described intermediate and advanced
      telemarkers accounted for 74% of the injured. In 96% of the injuries, the skier
      was performing a telemark turn. Powder snow or heavy, wet snow conditions were
      reported most often. Lower-extremity injuries were most common, accounting for
      42.5% (14) of the total. Seven of the lower-extremity injuries were ankle
      injuries, and four were knee injuries. Upper-extremity injuries comprised 24.2%
      (8) and head and facial injuries 21.2% (7) of the total. The least number of
      injuries occurred in the spine, 12.1% (4). Release plates were used by 8 of 28
      skiers and only released in two instances. Telemark skiers comprised 0.9% of
      skiers counted at the lifts during the 1995-1996 season and 1.8% in 1996-1997.
      Injury rates/1000 skier days in 1995-1996 were 3.3 (95% CI: 3.27, 3.35) for
      downhill skiers, 4.1 (95% CI: 3.32, 5.22) for telemark skiers, and 6.8 (95% CI:
      6.54, 7.00) for snowboarders. Injury rates/1000 skier days in 1996-1997 were 3.1
      (95% CI: 3.05, 3.15) for downhill skiers, 1.7 (95% CI: 1.44, 2.11) for telemark
      skiers, and 5.6 (95% CI: 5.39, 5.78) for snowboarders. We conclude that telemark
      skiers comprise only a small proportion of skiers at a lift-served area. Lower
      extremity injuries were most common, followed by upper-extremity and head and
      facial injuries. Injury rates for telemarkers are comparable to those for alpine
      skiers.

PMID- 11990164
TI  - Primary amebic meningoencephalitis: a review of the clinical literature.
AB  - Primary amebic meningoencephalitis (PAM) is a rapidly progressive and potentially
      fatal infection frequently contracted by swimming in bodies of warm fresh water.
      The etiological agent in most reported cases of PAM is the ameboflagellate
      Naegleria fowleri. Infection with this organism closely mimics and is often
      mistaken for a bacterial or a viral pyogenic meningitis. Recovery is rare and
      depends on rapid diagnosis and treatment. Physicians treating individuals who
      present with an acute pyogenic meningitis should consider the diagnosis of PAM,
      particularly if the patient has a recent history of swimming in warm fresh water.
      We review the recent literature for cases of PAM and the discuss ecology of N.
      fowleri and the clinical presentation, diagnosis, and treatment of PAM.

PMID- 11990165
TI  - Pulmonary ventilatory function decreases in proportion to increasing altitude.
AB  - The objective of this study was to examine how pulmonary ventilatory function,
      including response to bronchodilation, is related to altitude during high
      altitude trekking. This cohort experiment consisted of multiple spirometric tests
      before and after bronchodilation in participants at baseline (1624 m) and at
      different altitudes (3404-4896 m) during a 2-week trek. The setting was in the
      Himalayas. Eleven men (ages 22-68 years) and eight women (ages 19-42 years)
      participated. Interventions were at altitudes of 1624 m to 5265 m; albuterol was
      administered via Rotahaler. Forced vital capacity (FVC) decreased by an average
      of 3.8% [95% confidence interval (CI) 1.6 to 6.0] per 1000-m altitude increment.
      Forced expiratory volume in 1 second (FEV1.0) decreased 3.7% (95% CI 1.9 to 5.5)
      per each 1000-m altitude increment. Maximal midexpiratory flow rate (FEF25-75%)
      decreased by 3.6% (95% CI 0.9 to 6.3) per each 1000-m altitude increment. Small,
      postalbuterol flow increases were present at baseline and at altitude.
      Ventilatory function returned quickly toward baseline upon descent. One trekker
      developed cough, dyspnea at rest, extreme weakness, rales, tachycardia, and
      oxygen desaturation to 71%. His ventilatory measurements did not differ
      significantly (p > 0.32) from the group means. We concluded that changes in some
      pulmonary ventilatory parameters (FVC, FEV1.0, and FEF25-75%) were proportional
      to the magnitude of altitude during a high-altitude trek. These were tolerated
      well and do not seem to relate to acute mountain sickness. A bronchodilator
      effect was not increased at altitude.

PMID- 11990166
TI  - Lung pathology in high-altitude pulmonary edema.
AB  - Autopsy findings in 10 cases of high-altitude pulmonary edema have been collected
      from published articles and personal observations. All cases were males with a
      mean age of 37 years (22-62). The altitude of occurrence was from 8400 to 17 500
      feet. The mean combined lung weight in nine cases was 1682 g (1200-3000 g).
      Cerebral edema was present in five of eight cases. The most frequency pulmonary
      findings in addition to diffuse edema consisted of leukocyte infiltrates,
      alveolar hemorrhages, thrombi in small pulmonary arteries, and alveolar hyaline
      membranes. Pulmonary infarction was present in only one case. Right ventricular
      dilatation was commonly present. The left ventricle was normal. No significant
      coronary disease was present.

PMID- 11990167
TI  - Seizure and hemiparesis at high-altitude outside the setting of acute mountain
      sickness.
AB  - Neurologic problems at high altitudes are well known. What is probably less
      emphasized are neurologic problems at altitude outside the setting of high
      altitude cerebral edema. Because neurologic symptoms for these kinds of problems
      at high altitude are often transient, neuroradiologic scanning for these problems
      is usually not done or reported. Furthermore, diagnostic testing facilities may
      be unavailable in these remote high-altitude settings. A patient is described
      here with transient seizure and right-sided hemiparesis at high altitude with no
      preceding symptoms of acute mountain sickness. Computed tomography of the head
      was obtained in a hospital at lower altitude where the patient was taken
      promptly. The findings of the scan revealed probable focal cerebral edema in the
      left parietal lobe in keeping with his temporary right-sided weakness. Possible
      treatment modalities on the mountain for this problem are also discussed.

PMID- 11990168
TI  - Spontaneous recovery from severe neurotoxic envenoming by a Malayan krait
      Bungarus candidus (Linnaeus) in Thailand.
AB  - A patient bitten by Bungarus candidus (Malayan krait) developed nausea, vomiting,
      weakness, and myalgia 30 minutes after being bitten. One hour later, ptosis and
      occulomotor palsies as well as tightness of his chest were noted. Respiratory
      failure requiring mechanical respiration appeared 8 hours after the bite and
      lasted for nearly 96 hours. The two bite sites were virtually painless and
      resulted in slight transient erythema and edema. No specific antivenin was
      available, and treatment consisted of respiratory support and management of
      aspiration pneumonitis. Recovery was complete.

PMID- 11990169
TI  - Widow spider envenomation (latrodectism): a worldwide problem.
AB  - The objective of this study was to review widow spider envenomation on a
      worldwide basis, with an emphasis on regional variability in management,
      particularly between the United States and Australia. Data sources were the
      Medline database (1966-1997) for English language references using as key words
      widow spider, latrodectism, and red back spider, and Mesh headings. Textbooks of
      toxinology were also used. Studies involving clinical reports and series were
      selected. The data indicated that envenomation by widow spiders (latrodectism) is
      common worldwide. Local pain and sweating predominate, in about 25% of cases
      becoming generalized or developing in remote sites. The mortality in published
      series varies from 5% to 10%, although these may be overestimates. Australia may
      have the highest rate of latrodectism in the world. The literature reveals
      regional disparities in the treatment and outcome of latrodectism. In Australia,
      intramuscular antivenin has been used liberally for more than 40 years with a
      very low rate (0.5% to 0.8%) of allergic reactions and no deaths recorded since
      its introduction. Antivenin is routinely successful in relieving the effects of
      latrodectism. In the United States, the antivenin is given intravenously, is
      usually reserved for very severe cases, and the rate of allergic reaction is high
      (from 9% up to 80% in those skin testing positive). Deaths have been recorded
      after antivenin. The literature suggests that antivenin to one species of
      Latrodectus is likely to be effective against other species. The conclusion drawn
      was that latrodectism is a common envenomation worldwide. There is a strong case
      for a comparative trial of Australian vs US antivenin in treating latrodectism
      due to the black widow spider in the United States.

PMID- 11990170
TI  - Salvation on Mossy Creek.

PMID- 11990171
TI  - Increased aldosterone levels in acute mountain sickness at Capanna Regina
      Margherita.

PMID- 11990172
TI  - What every physician should know about environmental health.

PMID- 11990173
TI  - EMS in rural settings: a program to advance EMS in Yellowstone National Park.

PMID- 11990174
TI  - Teaching tropical medicine in Kenya and Uganda: review after seven expeditions.

PMID- 11990175
TI  - Injuries sustained during competitive white-water paddling: a survey of athletes
      in the 1996 Olympic trials.
AB  - To examine injury prevalence in competitive paddlers, a cross-sectional,
      retrospective, written survey of the athletes competing in the four regional
      Olympic canoe and kayak qualifying races for the United States Canoe and Kayak
      Team was conducted in the spring of 1996. A total of 375 questionnaires were
      distributed, of which 54 were completed and returned. Results were reported as
      the percentage of total injuries. A composite of 271 separate injuries was
      reported by kayakers during their careers. While 56% of the injuries occurred
      during training, 40% happened during recreation and 4% during competition. The
      most frequent injuries were sprains (32%), tendonitis (20%), and chronic
      musculoskeletal pain (14%). Simple bruises (9%) and infections (8%) occurred with
      moderate frequency, while severe injuries, such as dislocations (3%) and
      lacerations (2%), were even less common. About 10% of the paddlers noted a near
      drowning event during their careers. Of the injuries noted, 70% were reported as
      recurrent or chronic. Treatment included rest (37%), physical therapy (23%),
      medical intervention (34%), and surgical intervention (6%). White-water paddling
      of canoes and kayaks is a potentially dangerous sport, and competitive paddlers
      frequently suffer a range of injuries. Most injuries occurred during training;
      however, the short intense work of racing produced a greater frequency of
      injuries.

PMID- 11990176
TI  - Mountain medicine education in Europe.
AB  - All educational programs in mountain medicine in Europe are presented with their
      history, evolution, and current status. A comparison and a summary of those
      programs, as well as an estimate of the number of doctors trained in mountain
      medicine, are offered. Special focus is put on new developments and subspecialty
      programs. All programs listed in the Union Internationale des Associations
      Alpinistes (UIAA) information papers and all programs known through different
      publications were contacted and asked to forward information about recent
      courses, materials from former courses, and program syllabi. This information was
      reviewed and different specific topics were developed in depth. There are 13
      different programs in Europe offering medical education in mountain medicine: 3
      in France; 2 each in Italy, Spain, and the United Kingdom; and 1 each in
      Switzerland, Austria, Germany, and The Netherlands. The duration of these courses
      varies from a long weekend to a full 3-week course with theoretical and practical
      instruction. At this moment, most programs still have different contents and
      structures, which are being standardized by the UIAA and the International
      Commission for Alpine Rescue Medical Commission (ICAR MEDCOM). At least 2600
      doctors have had a first-contact course in high-altitude medicine, and at least
      2000 have participated in a full course of 1 week of more. A large number of
      doctors in Europe have become acquainted with mountain medicine by participating
      in different medical education programs. These programs should be optimized and
      further specialized in the different areas of mountain medicine, including
      expedition, alpine, and rescue medicine.

PMID- 11990177
TI  - Injury in traditional and sport rock climbing.
AB  - The objective of this study was to compare patterns of injury found in
      traditional rock climbing with those found in sport climbing. A questionnaire was
      administered to rock climbers by mail, in person, and via the World Wide Web.
      Injuries that occurred while rope-protected climbing on rock were analyzed
      regarding the anatomical location and the mechanism and activity at the time of
      injury. Ninety-four climbers reported sustaining an injury while rope-protected
      climbing on rock. Most injuries occurred while leading and involved the upper
      extremity, especially the fingers. Falling was the predominant mechanism of
      injury on traditional climbs, and stress over a joint while attempting a
      difficult move was the most common mechanism on sport climbs. Potential for
      injury prevention lies in teaching climbers to recognize the limitations of the
      fingers as weight-bearing structures.

PMID- 11990178
TI  - Altitude-related illness in two California national parks.
AB  - High-altitude illness encompasses a spectrum of disorders related to the hypoxia
      experienced by individuals at elevation. Altitude-related illness has been well
      described in the United States, but there are no studies published in the medical
      literature looking at the occurrence of high-altitude illness within the US
      National Parks system. The purpose of this study is to describe the incidence,
      treatment, and outcomes of visitors to Sequoia and Kings Canyon National Parks
      who presented to emergency medical services (EMS) personnel with signs and
      symptoms consistent with high-altitude illness. We conducted a retrospective
      review of all EMS patient care records (PCRs) from Sequoia and Kings Canyon
      National Parks during the study period of June 1992 to August 1995. There were 23
      cases of altitude-related illness identified by EMS personnel in the parks during
      the 38-month study period, including five cases of high-altitude pulmonary edema
      and 19 cases of acute mountain sickness. One patient died, nine patients were
      transported to local hospitals, nine patients were assisted in their descent and
      then released from medical care, and four patients were treated and then allowed
      to continue their travels. There was an average of 5.9 cases per year of high
      altitude illness and an incidence of one case per 27 EMS contacts. We conclude
      that altitude-related illness does occur in Sequoia and Kings Canyon National
      Parks and, although high-altitude illness accounts for only 4% of EMS contacts,
      caring for these patients uses a significant amount of national park resources.
      We suggest continued training of emergency medical technicians and park medics in
      the recognition and treatment of these disorders. We also support education of
      hikers to reduce or prevent the morbidity associated with altitude-related
      illness.

PMID- 11990179
TI  - Ophthalmomyiasis in Oman: a case report and comments.
AB  - A case of external ophthalmomyiasis caused by the first instar larvae of the
      sheep nasal botfly (Oestrus ovis) has been reported for the first time from the
      Sultanate of Oman, Southern Arabia. Sixty larvae were removed from the left eye
      of a 21-year-old male student, who acquired the infection during a field trip.
      The manual removal of larvae using a swab stick was the only effective treatment.
      The larval characteristics are described with illustrations, and the status of O
      ovis ophthalmomyiasis in the Middle East is discussed. The folk treatment
      administered for fly-mediated ophthalmomyiasis in Oman is also reported.
      Ophthalmomyiasis may not be a serious public health problem in Oman, but a
      nationwide survey of all myiases may be worthwhile.

PMID- 11990180
TI  - Up close and personal.

PMID- 11990181
TI  - Further musings on the sites, signs, and stereoscans of Dermatobia hominis.

PMID- 11990182
TI  - Hyponatremia in a cold environment.

PMID- 11990183
TI  - The piglet as an animal model for hypobaric hypoxia.
AB  - The objective of this study was to evaluate the piglet as a suitable animal model
      for human diseases of high altitude. We studied 12 piglets, 4-10 weeks old, in a
      hypobaric chamber under conditions of high altitude at a pressure of 1/2
      atmosphere (to approximately 320 Torr) for various periods of time (12, 24, 36,
      48, and 72 hours) with continuous monitoring. The animals were decompressed every
      24 hours for grooming and feeding. Two animals were studied as nonexposed
      controls, and one was studied as a control in the chamber without decompression.
      The animals were euthanized after the exposure, and a complete autopsy was
      performed. The tissues were then analyzed with light and electron microscopy. The
      animals all exhibited clinical features of ataxia, tachypnea with Cheyne-Stokes
      respiration, and lethargy. One animal vomited. The histologic and ultrastructural
      analysis showed normal organs, particularly lung and brain. The piglet may be a
      suitable animal model for the study of high altitude-related diseases in humans,
      but prolonged uninterrupted exposure and a delay in euthanasia after exposure to
      high altitude may be necessary for the development of reactive pathologic
      changes.

PMID- 11990184
TI  - Model for environmental heat damage of the blood vessel barrier.
AB  - Environmental heat stress may result in loss of fluid from the vascular space,
      which can lead to circulatory shock. Since the endothelium serves as the blood
      vessel barrier between the vascular and interstitial spaces, direct heat damage
      to this tissue may contribute to such fluid loss. This study modeled heat
      influences on the actin cytoskeletal proteins that provide the tensile forces
      that sustain endothelial junctional integrity or barrier function. Heat effects
      on bovine aortic endothelial cell (BAEC) F-actin and F-actin stress fibers
      (FASFs) were correlated with intercellular permeability (IP). F-actin
      concentration and FASF distribution were analyzed by quantitation of the specific
      binding of rhodamine phalloidin (RP) to F-actin and by observing the fluorescence
      of RP-FASF complexes, respectively. Dextran fluorescein IP was determined. The IP
      was elevated (p < 0.05) at 43 degrees C, but not at 41 degrees C. At 43 degrees
      C, BAECs were rounded and had disrupted FASFs and diminished cell-to-cell
      apposition. Similar cells were seen at 41 degrees C, but these were interspersed
      among FASF-containing cells to sustain apposition. Thus, disruption of FASFs
      correlated with increases in IP. F-actin was increased (p < 0.05) after
      hyperthermia. Since G-actin is more susceptible to irreversible heat
      denaturation, F-actin sustainment may function to preserve the actin pool and
      prevent irrevocable loss of the blood vessel barrier after heat stress.

PMID- 11990185
TI  - Evaluation of three commercial tick removal tools.
AB  - OBJECTIVE: To evaluate three commercially available tick removal tools against
      medium-tipped nontissue tweezers. METHODS: We evaluated three commercially
      available tick removal tools against medium-tipped tweezers. Three inexperienced
      users randomly removed attached American dog ticks (Dermacentor variabilis Say)
      and lone star ticks (Amblyomma americanum L.) from laboratory rabbits in a
      university animal facility using all tools during one removal session. RESULTS:
      Tick damage occurring from removal and quantity of attachment cement were
      compared. No tool removed nymphs without damage and all tools removed adults of
      both species successfully. American dog ticks proved easier to remove than lone
      star ticks, whose mouthparts often remained in the skin. CONCLUSIONS: Nymphal
      ticks were consistently removed more successfully with commercial tools when
      compared with tweezers but with more difficulty than adults were removed. The
      commercial tick removal tools tested are functional for removal of nymphs and
      adults and should be considered as viable alternatives to medium-tipped tweezers.

PMID- 11990186
TI  - Partitioned weight loss and body composition changes during a mountaineering
      expedition: a field study.
AB  - Weight loss and changes in body composition are recognized phenomena associated
      with high-altitude mountaineering expeditions. Attempts to partition the weight
      loss between fat mass (FM) and fat-free mass (FFM) have been inconclusive.
      Therefore, five male subjects, average age 40.0 +/- 5.5 years, were studied prior
      to, during, and following a 21-day expedition between 2200 m and 4300 m on Mt.
      McKinley, Alaska. Pre- to postexpedition body composition changes were determined
      by densitometry, skinfold thickness (12 sites), body girth measurements (14
      sites), and cross-sectional area from magnetic resonance imaging (MRI) (three
      sites). Data analysis by Student's t-test (p < 0.05(1) tail) indicated decreases
      in body weight (4.2 +/- 2.8 kg, 220 g/day, 5.4% of initial weight), total
      skinfold thickness (10.8%), total body girth (2.8%), and percentage of fat by
      densitometry (15%). Total cross-sectional area of the three MRI slices (upper arm
      + thigh + calf) decreased 4.7%, muscle area decreased 9.1%, and fat area
      decreased 3.9%. The three methods used to partition the weight loss between FM
      and FFM did not agree: 77% FM vs 23% FFM by densitometry, 25% FM vs 75% FFM by
      skinfolds, and 38% FM vs 62% FFM by MRI. Energy intake (3640 +/- 1250 kcal/day)
      was negatively correlated (Pearson r > 0.88(2) tail) with losses in weight (r = 
      0.89), skinfolds (r = -0.93), and girths (r = -0.88), ie the greater the intake
      the less the decline. Therefore, insufficient energy intake appeared primarily
      responsible for the weight loss and changes in body composition during the
      expedition.

PMID- 11990187
TI  - Amnesia during cold water immersion: a case report.
AB  - This report describes a case of amnesia during a cold-water experiment. The
      volunteer was exposed three times in 1 day (120 min duration each time) to 20
      degrees C water. During the third immersion, from min 95 to min 115, the subject
      experienced transient global amnesia for 20 min. The rectal temperature during
      this time was 35.6 degrees C. This single case demonstrates that memory loss in a
      young individual apparently can occur after cold-water exposure and at core
      temperatures above 35 degrees C.

PMID- 11990188
TI  - Medical experiences in Peru. 1960.

PMID- 11990189
TI  - Tragedy on Ptarmigan Peak.

PMID- 11990190
TI  - Acetazolamide for tourists to Lhasa.

PMID- 11990191
TI  - Near-infrared spectroscopy in the assessment of cerebral oxygenation at high
      altitude.
AB  - Hypoxia plays a key role in the pathogenesis of acute mountain sickness (AMS),
      but individual susceptibility is variable and cerebral symptoms do not always
      correlate with PaO2 measurements. Cerebral hypoxia may be more relevant than
      PaO2. We studied trends in cerebral regional oxygen saturation by the technique
      of near-infrared spectroscopy in 20 subjects ascending rapidly to 4680 m.
      Subjects were enrolled in a placebo-controlled, double-blind trial of
      medroxyprogesterone for the prevention of AMS. The fall in cerebral oxygen
      saturation was less than in the periphery. At 4680 m, cerebral oxygenation
      correlated with peripheral saturation but not with PaCO2 or with cerebral
      symptoms scores. At 4680 m, subjects on medroxyprogesterone had higher cerebral
      and peripheral saturation compared with those on a placebo. We conclude that
      cerebral oxygenation monitored with the Critikon 2020 system provided important
      information on the complex relationship of hypoxia to AMS and that other factors,
      such as changes in blood flow or capillary permeability, may be equally
      important.

PMID- 11990192
TI  - The perceptual and physiological responses of high and low fat women exposed to 5
      degrees C air for 120 minutes.
AB  - The present investigation dichotomized female subjects by percentage of fat (low
      fat [LF] = 19.2+/-3% [n = 4] vs high fat [HF] = 29.9+/-3% [n = 4]) to elucidate
      the perceptual and physiological responses during acute exposure to 5 degrees C
      air for 120 min. Correlational analyses were used to assess the relationship
      between thermal sensection (TS) and differences between LF and HF groups.
      Significant (p < 0.01) differences existed between the groups for TS when values
      were pooled over time, where HF had a lower TS (5.9+/-0.6) than LF (7.9+/-0.5).
      Additionally, a significant (p < 0.01) main effect for time existed, where TS,
      when pooled over groups T5 (3.8+/-0.7) and T30 (5.4+/-0.9), was less than T60
      (7.4+/-0.6), T90 (8.6+/-0.5), and T120 (9.1+/-0.4). No significant fat x time
      interaction was noted despite apparent perceptual differences between the groups
      at most of the time points. Further, the relationships between TS and percentage
      of fat and fat mass were either significant or exhibited strong trends toward
      significance at time points T5, T30, and T60. When rectal temperature (Tre) was
      pooled over the four time points, the fat groups differed significantly (p <
      0.05); LF (-0.21+/-0.04 degrees C) exhibited a greater ATre than HF (-0.03+/-0.04
      degrees C). When Tre was pooled across the fat groups, significant (p < 0.01)
      differences over time were detected. From these data, it appears that the
      modified TS scale tested may be a good marker of thermal discomfort in females
      exposed to the cold because perceptual differences were noted between the groups,
      accompanied by apparent differences in Tre between the LF and HF groups.

PMID- 11990193
TI  - Images. Brown recluse spider bite (necrotic arachnidism).

PMID- 11990194
TI  - "Puss caterpillar" envenomation: a report from North Carolina.
AB  - A 41-year-old white man with no specific past medical history presented to the
      Emergency Department on October 13, 1997, following what he described as a
      "caterpillar bite." The insect was subsequently identified as a "puss
      caterpillar" (Megalopyge opercularis). The patient experienced immediate
      excruciating pain that radiated throughout his left arm and gradually spread to
      the left chest area. He presented to a nearby emergency department several hours
      later and received treatment. The patient was subsequently admitted for
      observation and released several days later. Viewed in the context of previous
      clinical reports, this case highlights the broad range of clinical symptoms that
      can result from the puss caterpillar sting.

PMID- 11990195
TI  - Clinical update on lightning injuries.

PMID- 11990196
TI  - "From Larrey to Mills": the road to rapid rewarming--a commentary.

PMID- 11990197
TI  - Frostbite: experience with rapid rewarming and ultrasonic therapy. 1960-1.

PMID- 11990198
TI  - "Blind" emergency cricothyrotomy in patients with complicating factors under
      adverse conditions.

PMID- 11990199
TI  - Grizzly bear and pepper spray: a word of caution.

PMID- 11990200
TI  - Observations on ophthalmomyiasis.

PMID- 11990201
TI  - Neuropsychologic impairment and MRI abnormalities associated with chronic solvent
      abuse.
AB  - OBJECTIVE: Individuals chronically abusing organic solvents have been reported in
      the medical literature for almost four decades to have a variety of neurological
      abnormalities. Most have been single case reports or studies in small numbers of
      individuals. The purpose of this study was to evaluate the neurologic and
      neuropsychologic effects of chronic solvent abuse in a larger group of
      individuals and compare the results to a control group of other drug abusers.
      Attempts to estimate a dose-response relationship between solvent abuse and
      either neuropsychological tests or magnetic resonance imaging (MRI) abnormalities
      were also undertaken. METHODS: A sample of 55 solvent abusers was compared to a
      sample of 61 users of other drugs, especially cocaine and alcohol, on a battery
      of cognitive and neuropsychological tests. Fifty of the solvent abusers and 51
      members of the comparison sample also underwent MRI of the brain. Comparisons
      were made by means of multivariate analysis of variance and covariance. RESULTS:
      Compared to the general population, both groups performed poorly, scoring below
      the mean on most neuropsychological measures. Solvent abusers performed more
      poorly than the comparison sample on measures of working memory and executive
      cognitive functions. Both groups showed evidence of abnormal MRI findings, but a
      greater percentage of the solvent abuse group showed such abnormalities. No clear
      dose-response relationship was seen between solvent abuse and abnormalities on
      neuropsychological tests, but a strong dose-response relationship was seen in the
      presence of MRI abnormalities. CONCLUSION: The findings in this study document
      widespread cognitive impairment, which could not be attributed to the effects of
      solvents entirely. These findings expand upon previous data regarding
      neurological abnormalities in solvent abusers, by demonstrating a dose-response
      relationship with MRI abnormalities. An unexpected finding was the high
      prevalence of neuropsychological impairment and MRI abnormalities among the
      comparison group. The results of this study has implications regarding low-level
      solvent exposure, as in the occupational setting, suggesting that MRI may be a
      more useful tool to sort out the presence of neurological abnormalities rather
      than neuropsychological tests. Since no dose-response relationship was seen
      between solvent abuse and neuropsychological testing, reliance upon these tests
      in assessing neurological injury from solvents is a highly dubious practice.

PMID- 11990202
TI  - Acetaminophen hepatotoxicity: the first 35 years.
AB  - The acetaminophen nomogram including its uses and limitations is discussed as
      well as the development of the N-acetylcysteine protocol. While it has taken many
      years to elucidate the genetic variability and true multiplicity of the
      cytochrome P450 "mixed function oxidase system" many publications early on looked
      at the enzyme system as a single entity. Numerous articles indicated that
      barbiturates, anticonvulsants, and others could induce "P450" and add to the
      toxicity of acetaminophen. It rapidly became apparent that just because "P450"
      was induced when measured as a whole, not all other substrates would have changed
      metabolic activity. The role of diet and ethanol induction and inhibition on
      CYP2E1, the enzyme of greatest interest for acetaminophen is multifaceted. The
      lack of enhancement of acetaminophen toxicity by phenytoin and in fact, the
      potential for reduction of toxicity with that agent is a good example of the
      evolution of our knowledge. Further complicating our understanding is the
      introduction of misleading terms such as "therapeutic misadventure" and other
      expressions of molecular intent. A critical understanding of the literature makes
      it clear that therapeutic doses of acetaminophen either alone or in the presence
      of inducers do not produce toxicity. While the community of clinical
      toxicologists is small, it needs to be more aggressive in making sure that
      physicians from other specialties and non-clinical toxicology colleagues
      understand the significance and implications of this science.

PMID- 11990203
TI  - Mechanism of respiratory insufficiency in pure or mixed drug-induced coma
      involving benzodiazepines.
AB  - OBJECTIVE: We tested the hypothesis that the mechanism of respiratory
      insufficiency in drug-induced coma involving benzodiazepines is an increase in
      upper airway resistance. METHODS: Eighteen nonintubated and seven intubated
      (control) patients were poisoned with hypnotic sedatives involving
      benzodiazepines. Neurological and respiratory parameters were measured by
      polysomnography before and after flumazenil. Flumazenil was administered as
      escalating bolus doses followed by a continuous infusion. RESULTS: Upon entry,
      Glasgow Coma Score was 7 +/- 1 in nonintubated and 5 +/- 1 in intubated patients.
      Snoring with flow limitation and obstructive apnea were recorded in 16 and 5
      among the 18 nonintubated patients, respectively. Central apnea was not observed.
      Total pulmonary resistance was 2.5-fold higher in nonintubated patients than in
      intubated patients. Total and resistive work of breathing (WOB) was significantly
      greater in the nonintubated group. Flumazenil bolus administration was associated
      with an improvement in Glasgow Coma Score from 7 +/- 1 to 13 +/- 1 in the
      nonintubatedpatients, and from 5 +/- 1 to 11 +/- in the intubated patients. Mean
      effective bolus doses were 0.3 +/- 0.1 mg in nonintubated patients and 0.6 +/-
      0.1 mg in intubated patients. Tidal and minute volumes increased significantly,
      and WOB decreased significantly in nonintubated patients. In nonintubated
      patients, the decrease in total WOB resulted from a significant decrease in
      resistive WOB. CONCLUSION: Drug-induced coma involving benzodiazepines is
      characterized by snoring with flow limitation and obstructive apnea. The
      mechanism of respiratory insufficiency in nonintubated patients with drug-induced
      coma involving benzodiazepines is an increase in upper airway resistance and WOB.

PMID- 11990204
TI  - A pilot study for the detection of acute ciguatera intoxication in human blood.
AB  - INTRODUCTION: Ciguatera fish poisoning arises from consumption of any of the 400
      species of tropical marine reef fish containing polyether toxins. No laboratory
      method is available for clinical diagnosis of acute ciguatera poisoning. The
      objective of this pilot study was to ascertain the potential usefulness of a
      bioassay to detect ciguatoxins in humans suspected of acute intoxication. We
      analyzed plasma of healthy volunteers (asymptomatic negative controls),
      participants with gastrointestinal (GI) illness but without recent fish
      consumption (symptomatic negative controls), and participants with GI illness who
      had recently consumedfish. MATERIALS AND METHODS: Blood samples, questionnaires,
      and consent forms were collected from 11 symptomatic negative controls and 86
      patients that visited emergency rooms in southern Puerto Rico over a 1-year
      period. Patients had consumed fish within 24 hour prior to the symptoms. Plasma
      samples were analyzed by a neuroblastoma cell bioassay that detects seafood
      toxins active at the sodium voltage-gated channel in a dose-dependent fashion.
      Concentrations were expressed in terms of brevetoxin-1 equivalents (ng PbTx-1
      equiv/mL). RESULTS: The mean plasma concentration of 14 asymptomatic negative
      controls was 39.4 ng PbTx-1 equiv/mL (range 2-74). Of 86 potential ciguatoxic
      patients who reported fish consumption, 43 had values within the range of normal
      volunteers, and 9 had concentrations in the nondiagnostic range (73.9-100 ng).
      Thirty-four patients (40%) had concentrations 3 standard deviations above
      asymptomatic negative controls (>100 ng PbTx-1 equiv/mL). They had a mean
      concentration of 1,074 +/- 244.5 ng PbTx-1 equiv/mL (range 101-7,056ng).
      CONCLUSION: Preliminary findings of elevated PbTx-1 equivalents in 40% of the
      patients with both ciguatera symptomatology and fish consumption in a
      geographical area where ciguatera is common suggest that the neuroblastoma
      bioassay may be a potential diagnostic tool for acute ciguatera intoxication.

PMID- 11990205
TI  - Effect of ethanol and pH on the adsorption of acetaminophen (paracetamol) to high
      surface activated charcoal, in vitro studies.
AB  - BACKGROUND: Paracetamol (acetaminophen) intoxication often in combination with
      ethanol, is seen commonly in overdose cases. Doses of several grams might be
      close to the maximum adsorption capacity of the standard treatment dose (50g) of
      activated charcoal. The aim of this study was to determine the maximum adsorption
      capacity for paracetamol for two types of high surface-activated charcoal
      [Carbomix and Norit Ready-To-Use (not yet registered trademark in Denmark) both
      from Norit Cosmara, Amersfoort, The Netherlands] in simulated in vivo
      environments: At pH 1.2 (gastric environment), at pH 7.2 (intestinal
      environment), and with and without 10% ethanol. METHODS: Activated charcoal, at
      both gastric or intestinal pHs, and paracetamol were mixed, resulting in
      activated charcoal-paracetamol ratios from 10:] to 1:1. In trials with ethanol,
      some of the gastric or intestinal fluid was replaced with an equivalent volume of
      ethanol, resulting in an ethanol concentration of 10% v/v. After incubation, the
      concentration of unabsorbed paracetamol was analyzed by high-performance liquid
      chromatography. The maximum adsorption capacity of paracetamol to activated
      charcoal was calculated as mg paracetamol adsorbed/g activated charcoal, using
      Langmuir's isotherm. RESULTS: Carbomix [95% confidence limits are shown in square
      brackets]: 623.7 [612.8;634.5] mg paracetamol adsorbed/g activated charcoal (pH
      1.2), 626.2 [611.6;640.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2);
      Norit Ready-To-Use: 693.6 [676.8;710.5] mg paracetamol adsorbed/g activated
      charcoal (pH 1.2), 722.6 [687.4;757.9] mg paracetamol adsorbed/g activated
      charcoal (pH 7.2). For experiments with ethanol (10% v/v) the results with
      Carbomix were 465.7 [449.2;482.2] mg paracetamol adsorbed/g activated charcoal
      (pH 1.2), 498.6 [481.8;515.6] mg paracetamol adsorbed/g activated charcoal (pH
      7.2); with Norit Ready-To-Use: 617.2 [606.6;627.7] mg paracetamol adsorbed/g
      activated charcoal (pH 1.2), 640.6 [624.9;656.4] mg paracetamol adsorbed/g
      activated charcoal (pH 7.2). CONCLUSION: Under conditions simulating immediate
      treatment with charcoal, a standard dose of 50 g of either of the two tested
      activated charcoals adsorbed a sufficient amount of paracetamol to be beneficial
      in the treatment of the majority of overdoses of this drug. For both types of
      activated charcoal, with or without ethanol, there was no significant difference
      in the adsorption of paracetamol at pH 1.2 and 7.2. Norit Ready-To-Use had a
      larger maximum adsorption capacity than Carbomix, and was not as sensitive as
      Carbomix to environmental changes (pH and ethanol). The presence of 10% ethanol
      lowered the adsorption capacity of the two tested activated charcoal preparations
      by an amount that might be clinically relevant in cases of intoxications by high
      gram doses.

PMID- 11990206
TI  - Toxicological interactions between alcohol and benzodiazepines.
AB  - BACKGROUND: We review recentfindings on the toxicological interactions between
      alcohol (ethanol) and benzodiazepines, and the combined use of benzodiazepines
      and alcohol in fatal poisoning. Acute ingestion of alcohol combined with
      benzodiazepines is responsible for several toxicological interactions that can
      have significant clinical implications. In general, metabolism of these drugs is
      delayed when combined with acute alcohol ingestion although some reports suggest
      otherwise. Alternately, the drugs metabolized during chronic alcohol ingestion
      have an increased clearance. The net effect may also be influenced by internal
      (e.g., disease, age) and external (e.g., environment, diet) factors. Fatal
      poisoning involving coadministration of alcohol and benzodiazepine, especially
      triazolam, continues to be a serious problem.

PMID- 11990207
TI  - Treatment of a 1,4-butanediol poisoning with fomepizole.
AB  - BACKGROUND: Toxicity of 1,4-butanediol, an industrial solvent and a substance of
      abuse, is still misunderstood and not well documented. To date, only supportive
      treatments are used in this poisoning. CASE REPORT: The case of a 43-year-old man
      who ingested 30 mL of a homemade 1,4-butanediol solution and who developed
      general seizures and coma has been reported here. An intravenous loading dose of
      fomepizole 10 mg/kg was started on admission and followed by two other doses of
      10 mg/kg every 12 hour. He awoke shortly after fomepizole administration. Initial
      plasma 1,4-butanediol and gamma-hydroxybutyric acid concentrations, measured by
      gas chromatography-mass spectrometry, were 24 and 222 mg/L, respectively.
      Subsequent 1,4-butanediol and gamma-hydroxybutyric acid determination suggest
      that there was some further formate of gamma-hydroxbutyric acid after fomepizole
      was administered. CONCLUSION: Fomepizole administration appeared safe in this 1,4
      butanediol-intoxicated patient. It is unknown whether fomepizole influenced his
      clinical course, but the rapid awakening observed suggests that it may have been
      usefuL Further experience is needed, however, to define the efficacy of this
      antidotal therapy in 1,4-butanediol intoxication.

PMID- 11990208
TI  - Status epilepticus after massive carbamazepine overdose.
AB  - We report two patients who experienced status epilepticus after carbamazepine
      overdose. The first patient was an 18-year-old female with a history of epilepsy.
      She experienced 4 hour of persistent and prolonged seizures resistant to sodium
      amytal therapy. The status epilepticus ended with her death. The second patient
      was an 18-year-old male with a history of bipolar disorder. He experienced 5 hour
      of persistent and prolonged seizures that appeared to be resistant to diazepam,
      phenytoin, and phenobarbital. The seizures abated with the infusion of midazolam.
      This is a report of status epilepticus associated with wide complex tachycardia
      after carbamazepine overdose, which may be resistant to conventional therapy.

PMID- 11990209
TI  - Postcollection rise in methemoglobin level in frozen blood specimens.
AB  - A patient with nonspecific complaints had four previous venous blood samples
      showing elevated methemoglobin fractions of 15.6-20.1%. Cooximetry on a fresh
      specimen revealed a methemoglobin fraction of 0.8%, while that reported by the
      original laboratory on the simultaneously collected specimen was 14.9%. The
      laboratory assayed the specimen after holding it in frozen storage. Venous blood
      from a healthy volunteer was assayed by cooximetry after storage under conditions
      of room temperature (22-24 degrees C), refrigeration (1-4 degrees C), and
      freezing (-14 to -12 degrees C). Methemoglobin level in frozen-thawed specimens
      rose over time from 1.8% (0.29 g/dL) at 6 hour to 10.9% (1.71 g/dL) after 6 days.
      With the exception of a single specimen stored in an EDTA-containing tube at room
      temperature for 6 days, methemoglobin in nonfrozen specimens never exceeded 0.8%
      (0.12 g/dL).

PMID- 11990210
TI  - A primer on before-after studies: evaluating a report of a "successful"
      intervention.

PMID- 11990211
TI  - Delayed discharge: when is it important?

PMID- 11990212
TI  - Pharmaceutical care and health care utilization in an HMO.
AB  - CONTEXT: The belief that expanding the role of pharmacists in patient care could
      improve the safety and efficacy of drug therapy is growing. Specifically,
      pharmaceutical care programs through which pharmacists provide direct and ongoing
      counseling to patients have been introduced. Whether such programs reduce
      medication-related problems or health care utilization is unknown. OBJECTIVE: To
      assess whether a pharmaceutical care program decreases health care utilization,
      medication use, or charges. DESIGN: Nonrandomized, controlled trial. SETTING:
      Staff clinic and freestanding contract pharmacies affiliated with a large HMO in
      greater Minneapolis-St. Paul (6 intervention pharmacies, 143 control pharmacies).
      STUDY POPULATION: Adult HMO enrollees (n = 921) with heart or lung disease who
      used one of the selected pharmacies. INTERVENTION: Patients at intervention
      pharmacies were invited to participate in the pharmaceutical care program. The
      protocol-based program consisted of scheduled meetings between trained
      pharmacists and patients to assess drug therapy, plan goals, and intervene
      through counseling and/or consultation with other health professionals. OUTCOME
      MEASURES: Change in number of outpatient clinic visits, unique medications
      dispensed, and total charges over 1 year of follow-up. RESULTS: In an intention
      to-treat analysis (after adjustment for gender, age, Charlson Comorbidity Index,
      disease category, and the baseline value of the utilization measure), the number
      of unique medications for patients in the pharmaceutical care group increased
      more than in the usual care group (1.0 vs. 0.4 unique medications; P = 0.03).
      There was no difference between the two groups in the change in total number of
      clinic visits or total costs. In secondary adherence analyses, participants were
      more likely than the usual care group to increase the number of clinic visits
      (1.2 vs. -0.9; P = < 0.01) and number of unique medications (1.0 vs. 0.2; P =
      0.02). CONCLUSION: Pharmaceutical care for patients with chronic health
      conditions appears to be associated with a modest increase rather than a decrease
      in health care utilization.

PMID- 11990213
TI  - Benchmarking the future generalist workforce.
AB  - CONTEXT: Previous workforce analyses by the Council on Graduate Medical Education
      (COGME) have concluded that the United States has too few, or just enough,
      generalists. However, recent trends suggest that more physicians are entering
      primary care, raising the possibility of a future surplus. OBJECTIVE: To project
      the future supply of generalists relative to future requirements. DESIGN: We
      developed a model that projects the supply of generalists into the future on the
      basis of the annual number of physicians entering and leaving the workforce. We
      calculated the number of clinically active generalists from the physician master
      files of the American Medical Association and American Osteopathic Association.
      The number of graduating trainees entering the generalist workforce was
      calculated from the 1999 to 2000 AMA Annual Survey of GME. The number leaving was
      calculated by using age- and sex-specific rates or physician death and retirement
      provided by the Bureau of Health Professions. MEASUREMENTS: Projected per capita
      number of clinically active generalists to the year 2025, relative to physician
      requirements suggested by COGME and several regional benchmarks of physician
      supply. RESULTS: The supply of generalists is projected to grow from its current
      level of 69 per 100,000 to nearly 88 per 100,000 by the year 2025. Adjusting for
      the changing age-sex structure of the physician workforce decreases the
      "effective" supply to 85 generalists per 100,000. By the year 2025, the effective
      supply of generalists will exceed COGME's upper estimate of generalist
      requirements (80 per 100,000), resulting in an excess of about 18,000 full-time
      equivalent generalists. The future supply of generalists will also exceed most
      current regional benchmarks of generalist supply. CONCLUSION: At current levels
      of training, the supply of generalists will grow substantially and soon exceed
      several benchmarks for generalist requirements.

PMID- 11990214
TI  - Will electronic order entry reduce health care costs?

PMID- 11990215
TI  - Behavioral medicine: the challenge of integrating psychological and behavioral
      approaches into primary care.

PMID- 11990216
TI  - Expected adverse events in a mass smallpox vaccination campaign.
AB  - CONTEXT: Recent anthrax attacks in the United States have raised concern about
      the nation's vulnerability to a smallpox attack. Many strategies have been
      suggested to minimize the impact of such an attack, ranging from quarantine and
      vaccination of case contacts to resumption of routine vaccination. Before the
      latter strategy is adopted, an understanding of the likely consequences of mass
      vaccination is essential. COUNT: Number of adverse events resulting from two
      vaccination campaigns: vaccinating persons 1 to 29 years of age and vaccinating
      those 1 to 65 years of age. CALCULATION: Number of adverse events = incidence
      rate of adverse events x number vaccinated. We assumed 75% vaccine uptake in the
      target group (i.e., we estimated that about 25% of potential vaccine recipients
      would be excluded because they are, or have close contact with, individuals who
      have eczema or are immunocompromised). DATA SOURCE: Historical data on the
      incidence of adverse events from smallpox vaccination were identified by a
      literature search. Number vaccinated was drawn from the January 2000 U.S. Census
      estimate. RESULTS: Fever (<1 case per 5 vaccine recipients) and rash (<1 case per
      100 vaccine recipients) would be the most common adverse events. Serious adverse
      events, including encephalitis (<3 cases per million) and death (<2 cases per
      million), although rare, would be more common than with other currently
      recommended vaccines. After excluding high-risk individuals and their contacts,
      we estimate that a vaccination strategy directed at people aged 1 to 29 years
      would result in approximately 1600 serious adverse events and 190 deaths.
      Vaccinating people aged 1 to 65 years would result in approximately 4600 serious
      adverse events and 285 deaths. LIMITATIONS: While advances in health care over
      the past three decades could mitigate vaccine complications, the increased number
      of unimmunized high-risk individuals (e.g., those with eczema or immune
      suppression) could increase complication rates. CONCLUSIONS: The decision to
      resume smallpox vaccination depends on weighing the likelihood of a smallpox
      attack and its anticipated mortality against expected harm from a mass
      immunization program. Smallpox vaccine has a higher complication rate than any
      other vaccine currently being used. Careful prevaccination exclusion of high-risk
      individuals and their close contacts would be essential to minimize complications
      of a mass vaccination campaign, although such exclusions necessarily mean that
      some proportion of the population will remain susceptible to smallpox.

PMID- 11990217
TI  - The role of pharmacists in clinical care: where do we go from here?

PMID- 11990218
TI  - The delicate task of workforce determination.

PMID- 11990219
TI  - A mass smallpox vaccination campaign: reasonable or irresponsible?

PMID- 11990220
TI  - The child's route into reading and what can go wrong.
AB  - Two strands of linguistic development critically important for successful reading
      acquisition are outlined. One of these ontogenetic roots concerns phonological
      development and projects onto word decoding. The other root concerns the
      development of vocabulary and syntax projecting onto reading comprehension.
      Language development starts very early in infancy when the child learns to
      categorize the speech sounds according to the pattern typical of the mother
      tongue. Equipped with these sound categories the child is ready to learn to
      understand and to use new words. The precise phonological representation of words
      will facilitate the important development of phonological awareness. The paper
      reviews some longitudinal research and training studies indicating the causal
      direction of the relation between phonological awareness and reading. Preventive
      implications are pointed out. The preventive power of the second strand of
      development is discussed with reference to vocabulary exposure in different
      social environments and to informal early literacy socialization. In particular,
      the benefits of the prototypical situation of reading aloud to children are
      discussed. Finally, the complexity of the causal relationships between different
      aspects of early language development and later reading is pointed out.

PMID- 11990221
TI  - Evidence for an articulatory awareness deficit in adult dyslexics.
AB  - Dyslexia is widely considered to be associated with impaired performance on
      phonological awareness tasks. However, it is likely that orthographic knowledge
      also influences performance on these tasks. In this study, adult dyslexics, for
      whom reading is no longer a major problem, were compared to a control group on a
      measure of articulatory awareness, a task which is not confounded with
      orthography. The dyslexic group showed deficits on the task in comparison to the
      control group. We hypothesize that information about articulatory movements for
      specific phonemes is less accessible to dyslexics because of a deficient
      phonological processing system.

PMID- 11990222
TI  - Cross-linguistic transfer of phonological skills: a Malaysian perspective.
AB  - This study examined the phonological and reading performance in English of
      Malaysian children whose home language was Bahasa Malaysia (BM). A sample of 69
      Malaysian Standard Two pupils (aged 7-8 years) was selected for the study. Since
      commencing school at the age of 6 years, the children had been learning to read
      in BM and had subsequently also been learning to read in English for some 12
      months. The study was part of a larger scale research programme that fully
      recognized the limitations of tests that had not been developed and standardized
      in Malaysia. Nevertheless, as a first step to developing such tests, a comparison
      with existing norms for the Phonological Assessment Battery (PhAB) and the
      Wechsler Objective Reading Dimension (WORD) was undertaken in relation to
      information about the children's L1 and L2 language competencies. Results showed
      that the children's performance on PhAB was at least comparable to the UK norms
      while, not surprisingly, they fared less well on WORD. The results are discussed
      in terms of L1 and L2 transfer, whereby the transparency of written BM and the
      structured way in which reading is taught in BM facilitates performance on
      phonological tasks in English. This has implications for identifying children
      with phonologically based reading difficulties.

PMID- 11990223
TI  - The prevalence of dyslexia among art students.
AB  - It is widely held opinion that dyslexia is associated with remarkably artistic
      creativity. Speculations on different brain structures and brain functions have
      been proposed as an explanation. Very few objective studies have been reported
      that confirm the conjectures on the relationship between dyslexia and artistic
      creativity. Two studies are reported on the prevalence of dyslexia among
      university students-one group of art students and one group of students from non
      art disciplines. The admission to the art schools were extremely demanding,
      possibly implying that the students were genuinely talented, and that their
      choice of training did not reflect a compensation for failure in conventional
      academic fields. Art academy students reported significantly more signs of
      dyslexia than non-art university students. Objective testing showed that art
      students had significantly poorer phonological skills than non-art students.
      Thus, according to self-reports combined with objective testing, the incidence of
      dyslexia was far higher among art students.

PMID- 11990224
TI  - Evidence for implicit sequence learning in dyslexia.
AB  - Nicolson and Fawcett (Cognition 1990; 35: 159-182) have suggested that a deficit
      in the automatization of skill learning could account for the general impairments
      found in dyslexia. Much of the evidence for their claims has been collected via a
      dual task paradigm, which might allow for alternative explanations of the data.
      The present study examines automatic skill learning in a single task paradigm and
      extends previous studies by independently examining the contribution of stimulus
      based and response-based learning. The task replicates Mayr's (J. Exp. Psychol.:
      Learning Memory Cognition 1996; 22: 350-364) methodology in the Serial Reaction
      Time task by exposing participants to two structured displays, simultaneously.
      Learning is measured by comparing RT to the learned sequence against RT to a
      random display. This study demonstrates learning for both dyslexic and control
      groups for a spatial sequence which was observed and a concurrent non-spatial
      sequence which was responded to via a keypress. Learning of the sequence did not
      seem to depend on awareness of the sequence structure. These results suggest that
      automatic skill learning is intact in dyslexic individuals.

PMID- 11990225
TI  - The definition of dyslexia.

PMID- 11990226
TI  - Clinical features and atopy profile in Turkish subjects with analgesic
      intolerance.
AB  - The factors underlying analgesic intolerance (AI), particularly the role of
      ethnic characteristics, are readily not clear. In this trial, we aimed to assess
      the predictive features of AI in Turkish subjects. One hundred and ninety
      patients with AI were enrolled into the study conducted in our tertiary care
      clinic. The types of drug causing adverse reaction(s) and types of reaction(s)
      were recorded. The presence of atopy was assessed by skin prick tests. According
      to the results, the most frequently intolerated analgesic was acetyl salicylic
      acid (72.1%), followed by nonsteroidal anti-inflammatory drugs (68.4%) and
      paracetamol (15.8%). Urticaria/angioedema (52.6%) and asthmatic response (40.5%)
      were the most common reactions to analgesics. Compared with the general adult
      population of Turkey, the rate of atopy was found be higher in patients with AI
      and asthma (25% vs. 45%, p = 0.004) but comparable in patients with AI but no
      atopic disorder (25% vs. 29.2%, p> 0.05). In conclusion, subjects exhibiting
      intolerance to analgesics have particular features in our population; the
      presence of atopy in these subjects seems to be associated with the coexistent
      asthma rather than the drug allergy itself.

PMID- 11990227
TI  - Influence of sociodemographics on the health-related quality of life of pediatric
      patients with asthma and their caregivers.
AB  - The relationship between socioeconomic variables and the health-related quality
      of life (HQL) of children with asthma and their caregivers was examined. The
      Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Pediatric Asthma
      Caregivers Quality of Life Questionnaire (PACQLQ) were administered to 99
      pediatric asthmatic patients and caregivers in two specialty clinics.
      Sociodemographic data was obtained from medical records and additional questions.
      The relationship between sociodemographic variables and HQL was determined using
      multiple linear regression. The mean patient age was 12.6+/-2.1 years, more were
      male and from a minority race. The mean age of caregivers was 41.2+/-8.5 years;
      most were female and were fom a minority race. Patients tended to rate their
      asthma severity as mild to moderate, while caregivers tended to rate patients in
      the moderate to severe category. Based on prescribed medications, most patients
      had mild to moderate asthma. Household income was consistently associated with
      patient-perceived HQL. Less consistent associations were seen with other
      variables. Household income and the caregiver's perception of asthma severity
      were associated with all caregiver HQL domains. It was concluded that household
      income was most consistently associated with the HQL of asthmatic pediatric
      patients and their caregivers.

PMID- 11990228
TI  - The pattern of gastroesophageal reflux in asthmatic children.
AB  - The association between gastroesophageal reflux (GER) and asthma is not
      fortuitous. The objective of our study was to test a group of children with
      asthma by, 24 hr gastroesophageal pH monitoring and to relate the results to the
      patients medical history and clinical data. We studied 77 children aged from 39
      to 170 months suffering from particularly recurrent and/or therapy-resistant
      asthma. Medical history data were collected for each patient and included:
      severity and characteristics of respiratory symptoms, presence, if any of
      allergy; presence, if any, of GER-related symptoms; and presence, if any, of
      esophagitis-related symptoms. Esophageal pH was measured by 24 hr computerized
      monitoring of the main measures in all patients. Forty-seven children were also
      examined by gastroesophageal endoscopy. The prevalence of GER was 61% on the
      basis of the reflux index (cutoff: 4.2%). Gastroesophageal reflux in these
      asthmatic children was characterized mainly by short-lasting daytime episodes.
      The patients tended to present GER mainly associated with vomiting but not with
      signs and symptoms of esophagitis. The short-lasting nature of the reflux
      episodes demonstrates good esophageal clearance. The time of onset of respiratory
      symptoms (day/night) was not associated with any particular type of GER, the
      severity of which tends to be proportional to the seriousness of the asthma. No
      correlation was found between GER and allergy. No statistically significant
      differences were found in clinical or medical history findings between patients
      with pathologic and nonpathologic GER.

PMID- 11990229
TI  - Forced expiratory time and bronchial hyperresponsiveness to methacholine.
AB  - Pulmonary junction tests (PFTs) are normally performed prior to methacholine
      inhalation challenges (MICs). In contrast to normal baseline spirometry (FEV1,
      FEF25%-27%, FVC), we have observed patients with positive MICs having shortened
      forced expiratory times (FET100%) in the baseline pre-MIC PFT. We prospectively
      evaluated the correlation of abnormalities in baseline pre-MIC FET100% in
      patients who have positive vs. negative MICs. Prospective analysis of baseline
      pre- MIC FET100%, and MIC results in suspected asthmatics with normal lung exams,
      spirometry and chest x-rays. Using a PC20 FEV1 of < or =8mg/ml methacholine there
      were 115 positive and 69 negative MICs. The mean (+/-1 SD) FET100% in the
      positive MIC group was 3.57+/-1.68 sec vs. 4.73+/-1.60 sec in the negative group.
      The difference in these means was statistically significant (p <0.0001). There
      was a statistically significant difference in the incidence of FET100% <4sec in
      the positive (55.65%) vs. the negative (30.43%) MIC group, p<0.001. There was
      also a statistically significant difference in the incidence of positive MIC in
      FET100% <4sec (75.29%) vs. FET100%, > or =4sec (51.52%), p< 0.001. Our results
      suggest that in our highly selected, well-characterized population, FET100.%
      <6sec is common and FET100% <4 sec correlates with an increased likelihood of
      having a positive MIC.

PMID- 11990230
TI  - Inhaled corticosteroids and bone density of children with asthma.
AB  - In this cross-sectional study, we aimed to compare anteroposterior (AP) spine and
      total body bone mineral density (BMD) measurements of children with asthma
      treated with long-term inhaled budesonide (n = 52, mean age 6.4+/-2.2yr, M/F =
      22/30) (Group I) with those of asthmatic children who had never received
      treatment with inhaled corticosteroids (Group II) (n = 22, mean age 6.8+/-2.2,
      M/F = 10/12). Boys and girls were comparable for age, weight, height, cumulative
      corticosteroid (CS) dosage, duration of disease and inhaled corticosteroid (ICS)
      treatment within each group. The mean total accumulated dosage of budesonide for
      children in Group I was 154.0+/-135.3mg (mean daily dosage = 419+/-154 microg)
      and the mean treatment duration was 13.0+/-9.8 months. The two groups were
      comparable with respect to age, gender, weight, height, Tanner's stage and
      duration of disease. There was no significant difference between subjects in the
      two groups for total (p = 0.214) and (AP) spine BMD results (p = 0.661),
      respectively. Our results provide additional support for the safety of ICS
      therapy on bone density of asthmatic children.

PMID- 11990231
TI  - Increased interleukin-4 and decreased interferon gamma production in children
      with asthma: function of atopy or asthma?
AB  - Both atopy and asthma are claimed to be associated with a Th-2 cytokine pattern.
      We sought to determine the contribution of atopy and asthma to the observed Th
      2/Th-1 imbalance in these conditions. Of 60 children aged 6-16 years that were
      included in the study, 13 were nonatopic nonasthmatic, 15 atopic nonasthmatic, 14
      nonatopic asthmatic, and 18 atopic asthmatic. Atopic children had positive skin
      prick tests to grass pollens only. All children were studied after an
      asymptomatic and drug-free period of at least three months. Total IgE was
      measured in serum. Peripheral blood mononuclear cells were cultured and
      stimulated in vitro with phytohemagglutinin and interferongamma (IFN-gamma) and
      interleukin-4 (IL-4) measured in the supernatants. Total IgE was significantly
      higher in atopic asthmatics compared to nonatopic asthmatics (p = 0.004), and
      nonatopic nonasthmatics (p = 0.001), but was not different from atopic
      nonasthmatics (p >0.05). On the other hand, IL-4 was significantly elevated in
      atopic asthmatics and in nonatopic asthmatics compared to nonatopic nonasthmatics
      (p = 0.037 and p = 0.009, respectively). Although atopic asthmatics had lower IFN
      gamma values than nonatopic asthmatics, the difference did not reach statistical
      significance. No correlation was detected between any two parameters. Our results
      suggest that both atopy and asthma contribute to the increased levels of IL-4 and
      that, whereas nonatopic asthma is associated with increases in both IL-4 and IFN
      gamma release by mononuclear cells, only atopic asthma is characterized by a Th-2
      type cytokine dominance.

PMID- 11990232
TI  - An individualized intervention to improve asthma management among urban Latino
      and African-American families.
AB  - We hypothesized that an educational intervention based on a readiness model would
      lead to improved health outcomes among patients with asthma. Within a randomized
      control design in an urban Latino and African-American community we conducted an
      intensive three-month pediatric intervention. A Family Coordinator provided
      patient education based on a readiness-to-learn model, and facilitated improved
      interactions between the patient and the doctor. Family education addressed the
      most basic learning needs of patients with asthma by improving their perception
      of asthma symptom persistence using asthma diaries and peak flown measures. The
      physician intervention focused cliniciancs' attention on patients' diary records
      and peak flow measures, and encouraged physicians to use stepped action plans.
      Patients were also tested for allergic sensitization and provided strategies to
      reduce contact with allergens and other asthma triggers. The results showed
      significant improvements by intervention group families on measures of knowledge,
      health belief, self-efficacy, self-regulatory skill, and adherence; decreases in
      symptom persistence and activity restriction; and increased prescription of anti
      inflammatory medication by the physicians of the intervention group families.

PMID- 11990233
TI  - Effect of azithromycin on the severity of bronchial hyperresponsiveness in
      patients with mild asthma.
AB  - The effect of azithromycin on bronchial hyperresponsiveness was measured in a
      group of 11 patients with mild asthma. Azithromycin 250 mg orally was
      administered intermittently to all the patients twice a week for eight weeks. The
      only other treatment was inhaled beta2 agonist, when required. A histamine
      inhalation test was performed at the beginning and at the fourth and the eighth
      week of the study. The mean PC20 values increased significantly over the initial
      value at the eighth week after the administration of azithromycin (p < 0.05) but
      mean values for FEV1 and FEV1 percent predicted did not differ significantly.
      These results suggested that eight weeks of intermittent, low-dose administration
      of azithromycin in patients with mild asthma might reduce the severity of
      bronchial hyperresponsiveness.

PMID- 11990234
TI  - Nocturnal worsening of asthma and sleep-disordered breathing.
AB  - Asthma has a tendency, to destabilize and get worse at night, probably due to a
      nocturnal increase in airiway inflammation and bronchial responsiveness.
      Nocturnal airway narrowing in asthma is often associated with sleep disorders,
      such as episodes of nocturnal and early morning awakening, difficulty in
      maintaining sleep, and day time sleepiness. On the other hand, an association has
      been documented between nocturnal sleep-disordered breathing and asthma. This
      review highlights the causes of nocturnal worsening of asthma and examines the
      evidence pointing toward a causal relationship between nocturnal asthma and sleep
      disordered breathing.

PMID- 11990235
TI  - Neurologic illness associated with eating Florida pufferfish, 2002.
AB  - Since January 1, 2002, human illness after eating pufferfish caught in waters
      near Titusville, Florida, has been reported (Figure 1). The illnesses were
      manifested by neurologic symptoms consistent with exposure to paralytic shellfish
      toxins. Laboratory analysis in early April confirmed the presence of saxitoxin in
      uneaten pufferfish. This report presents selected case examples and summarizes
      all cases reported to the Toxic Exposure Surveillance System of the American
      Association of Poison Control Centers (TESS).

PMID- 11990236
TI  - Fatal yellow fever in a traveler returning from Amazonas, Brazil, 2002.
AB  - Yellow fever (YF) is a mosquitoborne viral disease that has caused deaths in U.S.
      and European travelers to sub-Saharan Africa and tropical South America. Although
      no specific treatment exists for YF and the case-fatality rate for severe YF is
      approximately 20%, an effective vaccine is available. This report describes a
      case of fatal YF in an unvaccinated traveler who had returned from a 6-day
      fishing trip on the Rio Negro west of Manaus in the state of Amazonas, Brazil.
      Because information from some commercial outfitters and travel agents might
      underestimate health risks, healthcare providers and travelers should review
      vaccination and other traveler's health recommendations from public health
      agencies.

PMID- 11990237
TI  - Preliminary FoodNet data on the incidence of foodborne illnesses--selected sites,
      United States, 2001.
AB  - An estimated 76 million persons contract foodborne illnesses each year in the
      United States. CDC's Emerging Infections Program Foodborne Diseases Active
      Surveillance Network (FoodNet) collects data about 10 foodborne diseases in nine
      U.S. sites to quantify and monitor foodborne illnesses. This report describes
      preliminary surveillance data for 2001 and compares them with 1996-2000 data. The
      data show a decrease in the major bacterial foodborne illnesses, indicating
      progress toward meeting the national health objectives of reducing the incidence
      of foodborne diseases by 2010. However, the data do not show a sustained decline
      in some infections, indicating that increased efforts are needed to reduce
      further the incidence of foodborne illnesses.

PMID- 11990238
TI  - Racial and ethnic disparities in infant mortality rates--60 largest U.S. cities,
      1995-1998.
AB  - During the 20th century, U.S. infant mortality rates (IMRs) declined by 90%;
      however, many of the largest U.S. cities continue to have high IMRs compared with
      national rates. Studies of U.S. infant mortality by region document persisting
      geographic disparities and differences across racial/ethnic groups. This report
      highlights the wide disparities in the most recent overall race- and ethnicity
      specific IMRs for the largest U.S. cities and describes key differences among
      those cities. The findings demonstrate the need to decrease infant mortality
      among blacks in U.S. cities.

PMID- 11990239
TI  - Longitudinal comparison of virus load parameters and CD8 T-cell suppressive
      capacity in two SIVcpz-infected chimpanzees.
AB  - In a longitudinal study we address the hypothesis that resis tance to disease
      progression in lentivirus-infected chimpanzees is related to potent non-cytotoxic
      suppression of virus replication. In a long-term follow-up, the viral suppressive
      capacity in two simian immunodeficiency virus (SIV)cpz-infected chimpanzees was
      correlated with two polymerase chain reaction (PCR)- and two culture-based virus
      load measurements. In both animals, quantitative virus isolation (QVI) tended to
      decline slowly, whereas in vitro virus suppression was sustained or increased
      over time. In general, plasma virus loads in SIVcpz-infected animals were
      maintained for extended periods of time. Based on current assays that measure
      virus suppressive capacity in peripheral blood, it was not possible to conclude
      that virus suppression played a major role in the maintenance of the disease-free
      state in lentivirus-infected chimpanzees.

PMID- 11990240
TI  - Chronic immune stimulation accelerates SIV-induced disease progression.
AB  - The contribution of chronic immune stimulation on the progression of lentivirus
      induced disease was evaluated in the SIVmac251 macaque model of AIDS. Following
      SIV inoculation, seroconversion and control of the acute viral replication phase,
      repeated immune stimulations with tetanus toxoid (TT), keyhole limpet hemocyanin
      (KLH) and allogeneic peripheral blood mononuclear cells (PBMC) were initiated in
      four monkeys. These animals showed a significant shortening of survival when
      compared with eight non-immune-stimulated control animals inoculated with the
      same route, dose and stock of SIVmac251 (median survival 9.5 months versus 17
      months, P = 0.010). In addition, when the comparison was extended to another 22
      control animals of different origin but inoculated by the same route with similar
      doses and stocks of SIVmac251, the difference in survival was still significant
      (9.5 versus 18 months, P = 0.003). This accelerated progression of symptomatic
      disease was not accompanied with significant increases in plasma viral loads, but
      suboptimal antibody responses to the immunizing antigens were noted, correlating
      with the length of survival. These findings may have implications for HIV
      infected humans suffering from chronic infectious diseases.

PMID- 11990241
TI  - Spontaneous amyloidosis in twelve chimpanzees, Pan troglodytes.
AB  - Spontaneous amyloidosis was diagnosed in 11 male and 1 female chimpanzees and
      confirmed histologically and immunohistochemically. The chimpanzees were > or =
      15 years of age when first diagnosed and averaged 22.4 years of age. The average
      survival time after diagnosis of systemic amyloidosis was 1.86 years with a
      standard deviation of 4.06 years (n = 7). The chimpanzees with amyloidosis were
      asymptomatic except for hepatomegaly, which became more detectable with age.
      Significant increases in clinical chemistry values, as compared with referenced
      normals and established normals, of blood urea nitrogen (BUN), asparate
      aminotransferase (AST), gamma-glutamyltransferase (GGT), globulin, total protein,
      creatinine phosphokinase (CPK), sedimentation rate, and triglycerides were found
      in animals 7 years of age or older with amyloidosis. These serum chemistry
      values, while increased in chimpanzees with amyloidosis, were generally within
      normal limits. Immunohistochemistry for both amyloid A protein and amyloid P
      component-labeled extracellular amyloid in all chimpanzees with amyloidosis was
      determined. Amyloid was deposited primarily in the liver. Amyloidosis in the
      chimpanzee is a chronic, intractable, progressive, fatal disease, and appears to
      be similar to secondary amy loidosis in other species.

PMID- 11990242
TI  - Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and
      histopathologic correlation.
AB  - Degenerative disc disease is a major source of disability in humans. The baboon
      model is an excellent natural disease model to study comparable human disease,
      because baboons are relatively large (adult males 20-26 kg, adult females 12-17
      kg), long-lived (30-45 years), well defined, easy to use, and closely related to
      humans. Published investigations with plain radiographs of disc degeneration in
      baboons indicated vertebral anatomy and changes that were remarkably similar to
      those seen in humans, and it would be valuable to determine if magnetic resonance
      imaging (MRI) and histopathologic evaluation would be useful methods for studying
      the model, as MRI allows multi-planar visualization of tissues without the use of
      intravenous contrast and it is superior for evaluating disc hydration, annulus
      tears, and herniations. The thoracolumbar junctions from 47 randomly selected
      baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and
      histopathology. Excellent correlation with MRI was observed for changes in disc
      desiccation, height, and age (P < 0.001). The pathologic analysis demonstrated P
      values of < 0.001 when comparing histopathology with age and MRI results. All
      severely degenerated discs seen by MRI were in baboons 14 years of age or older.

PMID- 11990243
TI  - Reproductive maturation in a sample of captive male baboons.
AB  - Though baboons have been considered an appropriate non-human primate model for
      studying human reproductive and endocrine development. the overall similarity of
      reproductive maturation between the two species is unclear. This paper examines
      the role of testicular and adrenal hormones for pubertal changes in a cross
      sectional sample of 21 captive male savanna baboons. Morphometric and hormonal
      indices demonstrate changes in size and gonadal function, but not adrenal
      function, during pubertal maturation among baboons. Results also indicate that
      gonadal, but not adrenal, androgens are related to morphometric variables. We
      conclude that savanna baboons do not make an appropriate evolutionary model of
      human pubertal maturation.

PMID- 11990244
TI  - Multi-tiered treatment of pressure sores in two cynomologous macaques (Macaca
      fascicularis).
AB  - Successful treatment of one Grade IlI and two Grade IV pressure sores on two
      female Macaca fascicularis, subsequent to a T11 hemilaminectomy and left spinal
      cord hemisection, was achieved through a combined strategy of wound care, diet,
      and husbandry. Wound care consisted of early and thorough debridement of all
      necrotic tissue, initial twice daily cleaning with an iodine scrub and
      application of a multi-ingredient ointment. Tissue hydrolyzer, a drying agent,
      vitamin E, ground selenium, and topical antibiotics were applied to the wound
      during the respective 45- and 46-day courses of treatment. Oral antibiotics were
      administered; vitamins C and E, and selenium were increased in the diet. No
      infection occurred and both animals recovered fully to complete the study.
      Importantly, pressure sores in subsequent study animals were prevented by post
      operative padding of the perch with towel-covered foam and placement of a
      wheelchair cushion on the floor of the cage.

PMID- 11990245
TI  - A rapid and systematic review of the evidence for the clinical effectiveness and
      cost-effectiveness of irinotecan, oxaliplatin and raltitrexed for the treatment
      of advanced colorectal cancer.

PMID- 11990246
TI  - Peripheral vascular diseases resulting from chronic arsenical poisoning.
AB  - Drinking water contaminated by arsenic remains a major public health problem.
      Long-term arsenic exposure has been found to be associated with peripheral
      vascular diseases in a variety of studies. Reports of vascular effects of arsenic
      in drinking water, which span almost 100 years, have been published in Taiwan,
      Chile, Mexico, and China. This paper reviewed the association of peripheral
      vascular diseases resulting from arsenic exposure to drinking water from the
      clinical and pathological points of view. An endemic peripheral vascular disorder
      called "blackfoot disease" has been noticed in a limited area in Taiwan. This
      disease results in gangrene in the extremities. It has been associated with the
      ingestion of high concentrations of arsenic-tainted artesian well water.
      Epidemiological studies confirmed a dose-response relationship between long-term
      arsenic exposure and the occurrence of blackfoot disease. Whereas arsenic has
      induced various clinical manifestations of vascular effects in Chile, Mexico and
      China, they do not compare in magnitude or severity to the blackfoot disease
      found in Taiwan. The pathogenesis of vascular effects induced by arsenic is still
      controversial. The possible mechanisms include endothelial cell destruction,
      arsenic-associated atherogenesis, carotene and zinc deficiency, and/or some
      immunological mechanism. Microcirculatory assessments revealed that deficits of
      capillary blood flow and permeability exist in clinically normal skin of patients
      with chronic arsenical poisoning. The vascular effects of chronic arsenic
      poisoning may involve cardiovascular and cerebrovascular systems as well. In view
      of the increasing public health problems caused by arsenic exposure, vascular
      effects should be included in the future study of health effects of arsenic.

PMID- 11990247
TI  - Immunohistochemical analysis of the infiltrated cells in tinea capitis patients.
AB  - Tinea capitis is a fungal infection of the skin and the hair with involvement of
      the hair shaft and the pilosebaceous unit. It may be the most common of all
      cutaneous mycoses in children. Tinea capitis can be inflammatory or
      noninflammatory. It is thought that humoral and cell-mediated immunities play a
      role in the formation of the clinical types of the disease. We studied twelve
      patients with acute inflammatory disease, four patients with chronic non
      inflammatory disease, and one patient with a black-dot variant of tinea capitis.
      The composition of inflammatory infiltrates present in lesional skin was analyzed
      by antibodies to T cells (CD3) and B cells (CD20). Anti-CD3 revealed large
      numbers of T cells in twelve patients with acute, inflammatory dermatophytosis,
      whereas anti-CD20 revealed marked infiltrates of both B and T cells in all
      patients with chronic, non-inflammatory dermatophytosis. As a result, we thought
      that cell-mediated immunity might play a role in the acute, inflammatory type of
      tinea capitis and that humoral immunity might do so in the chronic, non
      inflammatory type of tinea capitis.

PMID- 11990248
TI  - A novel nonsense mutation at E106 of the 2B rod domain of keratin 14 causes
      dominant epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is classified into three main types and is
      caused, in most cases, by missense mutations in the genes encoding keratin (K) 5
      and K14. In this study, we clinically, ultrastructurally, immunohistochemically,
      and molecularly studied a patient with a dominant EBS, Kobner type. Using
      sequence analysis of genomic DNA, a novel K14 nonsense mutation was identified. A
      heterozygous mutation G1231T of KRT14 was found to be associated with the disease
      in the patient. The mutation created a premature stop codon (amino acid codon
      411, residue 106 of the 2B helix) in the K14 molecule. This residue lies in a
      highly conserved region and was recently found to be absolutely required for
      molecular stability and intermediate filament assembly in K5 and K14. The E411X
      (E106X) heterozygous ablation, missing the last 16 amino acid residues of the 2B
      and the entire tail domain of K14, led to disease but did not result in clumping
      of keratin filaments. It is the first premature stop codon mutation of K14 found
      in dominant EBS.

PMID- 11990249
TI  - Short-term etretinate therapy for prurigo chronica multiformis.
AB  - Prurigo chronica multiformis is an intensely pruritic, chronic cutaneous disorder
      of unknown etiology without any effective treatment. This is a report on the
      results of using etretinate therapy to treat prurigo chronica multiformis. Thirty
      seven patients (average age; 69.1+/-11.5 year-old) were treated with 30 mg/day
      etretinate along with topical steroids (very strong classes) and oral
      antihistamines. Etretinate was discontinued as soon as remission was achieved.
      Thirty-six patients were followed up for at least four weeks. The number of
      patients who achieved remission increased progressively after the initiation of
      etretinate therapy; 18 patients were totally and 14 were partially free of active
      skin lesions within four weeks. Eventually, 27 patients achieved remission with
      an average duration of 4.4+/-3.1 weeks etretinate treatment (range; 1-14 weeks),
      and five achieved partial remission. Four patients discontinued etretinate within
      two weeks because of the absence of clinical response (two cases) or exacerbation
      of the skin lesion (two cases). Among the 27 patients who had achieved remission,
      23 had recurrence after the cessation of etretinate. The remission period ranged
      from 1 to 32 weeks with an average duration of 5.7+/-6.7 weeks. Combined
      treatment with topical steroids and oral antihistamines did not achieve remission
      in the recurrent cases but re-administration of 30 mg/day etretinate did. Our
      observation suggests that a moderate dose of etretinate is a safe and effective
      therapy for prurigo chronica multiformis, which is often resistant to
      conventional treatment using topical steroids and oral antihistamines.

PMID- 11990250
TI  - Clinical and histologic features of 64 cases of steatocystoma multiplex.
AB  - Steatocystoma multiplex (SM) shares many clinical features and may show
      overlapping histopathological features with eruptive vellus hair cyst (EVHC).
      Clinical data and pathologic features of 64 patients with SM were evaluated in
      detail. Most of the cases were sporadic, with an average onset age of 26 years
      and distribution on the arms, chest, axillae, and neck. All cases exhibited
      eosinophilic cuticle and lack of granular layer, and 17-42% displayed vellus
      hair, hair follicles, keratin, and smooth muscle components within the cavity, in
      the wall, or adjacent to it. The results of this study add further evidence to
      the hypothesis that SM is a hamartomatous condition and that SM and EVHC are
      variants of one disorder which originates in the pilosebaceous duct.

PMID- 11990251
TI  - Facial steatocystoma multiplex associated with pilar cyst and bilateral
      preauricular sinus.
AB  - A 30-year-old male presented with multiple, yellowish to skin-colored, firm to
      soft nodules on the forehead, temple, postauricular area and neck for the
      previous seven years. Examination of the scalp revealed a single, soft, cystic
      swelling on the occiput and the patient complained of occasional discharge from
      two, 0.1 x 0.1 cm, openings in front of both ears. Histopathology of the facial
      lesion was suggestive of steatocystoma multiplex, while that of the scalp
      revealed a pilar cyst. An otorhinolaryngeal evaluation confirmed the presence of
      bilateral pre-auricular sinus. We present this previously unreported
      pilosebaceous hamartoma, constituting facial steatocystomas and pilar cyst,
      associated with bilateral preauricular sinus.

PMID- 11990252
TI  - Palisaded and verocay body prominent leiomyoma of deep soft tissue.
AB  - Leiomyoma of deep soft tissue is a very rare tumor, which is sometimes confused
      with leiomyosarcoma, histopathologically. We describe a case of palisaded and
      Verocay-body prominent leiomyoma of deep soft tissue. The lesion was
      characterized by areas of nuclear palisading with Verocay-body like formation in
      addition to the features of leiomyoma.

PMID- 11990253
TI  - An unusual nail presentation in Marfan's syndrome.
AB  - Skin and nail lesions are very rare in Marfan's syndrome. We reported a 14-year
      old boy who presented with pterygium in the nails of both the upper and lower
      limbs with chest deformity along with other features of Marfan's syndrome.
      Histopathological findings revealed hyperkeratosis with a scant perivascular
      inflammatory infiltrate. It was not clear whether this case is the first
      presentation of pterigium in Marfan's syndrome or congenital lichen planus. To
      our knowledge, this kind of feature is the first Marfan's syndrome case of its
      kind.

PMID- 11990254
TI  - A keratin 10 gene mutation (Arg156Cys) in a Japanese patient with bullous
      congenital ichthyosiform erythroderma.
AB  - We described a 19-year old Japanese female with bullous congenital ichthyosiform
      erythroderma (BCIE) and examined the keratin gene mutation. Physical examination
      disclosed generalized erythema, ichthyosiform skin with scales, and erosions
      without palmoplantar keratoderma. Histological examination revealed
      hyperkeratosis with vacuolar degeneration in the granular layer of the epidermis.
      Sequence analysis demonstrated a C to G transition at the first position of codon
      156 in the keratin 10 gene. The amino acid at codon 156 was deduced to have
      changed from arginine to cystine. Substitution from arginine to cysteine at codon
      156 of the K 10 gene is assumed to be fatal for keratin filament assembly
      regardless of racial or ethnic difference.

PMID- 11990255
TI  - Hot pop brown spot: erythema Ab igne induced by heated popcorn.
AB  - Erythema ab igne is caused by chronic heat exposure and presents with reticulated
      pigmentation. Although various causes of erythema ab igne have been reported, in
      the United States, its incidence has been declining due to the advent of central
      heating. When seen, it is usually in the setting of local applications of a
      heated source, such as a hot water bottle, to treat muscular or arthritic pains.
      We report a novel cause of erythema ab igne occurring in a patient with chronic
      arthritic pains. This patient applied popcorn kernels, heated in a microwave, to
      his right wrist and knee for 30 minutes at a time for over four months.

PMID- 11990256
TI  - Lymphomatoid papulosis associated with Sjogren's syndrome.

PMID- 11990257
TI  - Zosteriform angiolymphoid hyperplasia with eosinophilia.

PMID- 11990258
TI  - Folliculitis decalvans: successful treatment with a combination of rifampicin and
      topical mupirocin.

PMID- 11990259
TI  - Ichthyosiform amyloidosis.

PMID- 11990260
TI  - Development and use of scoring systems for assessment of clinical competence.

PMID- 11990261
TI  - Role of the kidney in perioperative inflammatory responses.

PMID- 11990262
TI  - Anaesthesia and the Internet.

PMID- 11990263
TI  - Use of a high-fidelity simulator to develop testing of the technical performance
      of novice anaesthetists.
AB  - BACKGROUND: We used the Delphi technique to gain a consensus from 26 consultant
      anaesthetists about technical tasks during general anaesthesia. We then developed
      a technical scoring system to assess anaesthetists undertaking general
      anaesthesia with rapid sequence induction. METHODS: We then followed the
      performance of six novice anaesthetists on five occasions during their first 3
      months of training. At each, visit each novice 'anaesthetized' the Human Patient
      Simulator at Bristol Medical Simulator Centre. For comparison seven post
      fellowship anaesthetists were scored on one occasion. RESULTS: Novice scores
      improved significantly over the 12-week period (P<0.01). A significant difference
      was also found between the final novice scores and the post-fellowship subjects
      (P<0.05). CONCLUSIONS: These findings suggest that simulation can be used to
      observe and quantify technical performance.

PMID- 11990264
TI  - A prospective study of the quality of pre-hospital emergency ventilation in
      patients with severe head injury.
AB  - BACKGROUND: Pre-hospital endotracheal intubation for the purpose of controlled
      ventilation may prevent secondary brain injury in patients with severe head
      injury. In view of the limited monitoring devices utilized in the pre-hospital
      setting, little is known about the 'quality' of controlled ventilation initiated
      in the pre-hospital setting. METHODS: Included in this prospective study were 122
      trauma patients with severe head injury (abbreviated injury scale score > or =
      3). In all cases, the pre-hospital treatment included endotracheal intubation in
      the field. Upon hospital admission, and maintaining the same ventilation mode and
      setting initiated in the pre-hospital setting, arterial blood gas samples were
      taken. RESULTS: 'Optimal' oxygenation (PaO2 > 100 mm Hg) was achieved in 85.2%
      and 'adequate' ventilation (PaCO2 35-45 mm Hg) in 42.6% of the patients upon
      hospital admission. 'Optimal' oxygenation as well as 'adequate' ventilation was
      achieved in 37.7% of the study population. Hypoxaemia (PaO2 < 60 mm Hg) was
      observed in 2.5%, hypercapnia (PaCO2 > 45 mm Hg) in 16.4%, and hypocapnia (PaCO2
      < 35 mm Hg) in 40.9% of the study patients. The incidence of hypocapnia was
      significantly more frequent in polytraumatized patients. Hypocapnia as well as
      hypercapnia was significantly more frequent in patients with associated pulmonary
      contusion. CONCLUSIONS: Endotracheal intubation and controlled ventilation of the
      lungs initiated in the pre-hospital setting do not guarantee optimal oxygenaton
      and ventilation in patients with severe head injury.

PMID- 11990265
TI  - Continuous and intermittent cardiac output measurement: pulmonary artery catheter
      versus aortic transpulmonary technique.
AB  - BACKGROUND: Cardiac output (CO) can be measured intermittently by bolus
      thermodilution methods in the pulmonary artery (COpa) or in the aorta (COart). A
      continuous thermodilution method (CCO) and a method for continuous estimation
      using the arterial pulse wave (PCCO) are also available. METHODS: We compared two
      methods of intermittent CO measurements in patients during liver transplantation:
      COpa, regarded as the current clinical standard, and an aortic transpulmonary
      thermodilution technique (COart) performed with the PiCCO system. We also
      compared CCO and PCCO. Measurements were made in 62 patients at three stages:
      after the induction of anaesthesia, after caval clamping phase, and at the end of
      surgery. We used Bland-Altman and correlation analysis. RESULTS: We found close
      agreement between the techniques. Mean bias between COart and COpa and PCCO and
      CCO was 0.15 (2SD of differences between methods=1.74) litre min(-1) and -0.03
      (1.75) litre min(-1), respectively. Mean bias between CCO and COpa and PCCO and
      COpa was 0.02 (1.48) litre min(-1) and 0.04 (1.69) litre min(-1), respectively.
      CONCLUSIONS: Measurement with the aortic transpulmonary thermodilution technique
      gives continuous and intermittent values that agree with the pulmonary
      thermodilution method.

PMID- 11990266
TI  - Cerebrovascular carbon dioxide reactivity in children anaesthetized with
      sevoflurane.
AB  - BACKGROUND: To determine the effects of sevoflurane on cerebrovascular carbon
      dioxide reactivity (CCO2R), middle cerebral artery blood flow velocity (CBFV) was
      measured at different levels of PE'CO2 by transcranial Doppler sonography in 16
      ASA I or II children, aged 18 months to 7 yr undergoing elective urological
      surgery. METHODS: Anaesthesia comprised 1.0 MAC sevoflurane and air in 30% oxygen
      delivered through an Ayre's T piece by intermittent positive-pressure
      ventilation, and a caudal epidural block with 0.25% bupivacaine 1.0 ml kg(-1)
      without epinephrine. PE'CO2 was randomly adjusted to 25, 35, 45 and 55 mm Hg
      (3.3, 4.6, 5.9 and 7.2 kPa) with an exogenous source of CO2, while maintaining
      ventilation variables constant. RESULTS: CBFV increased as PE'CO2 increased from
      25 to 35, and to 45 mm Hg (P<0.001), but did not increase significantly with an
      increase in PE'CO2 from 45 to 55 mm Hg. Mean heart rate and arterial pressure
      remained constant. CONCLUSION: CCO2R is preserved in healthy children
      anaesthetized with 1.0 MAC sevoflurane.

PMID- 11990267
TI  - Recovery of memory after general anaesthesia: clinical findings and somatosensory
      evoked responses.
AB  - BACKGROUND: Mid-latency somatosensory evoked responses are used to monitor the
      integrity of the sensory pathways intra-operatively. They can quantify the
      effects of anaesthetics on the central nervous system. Mid-latency auditory
      evoked responses have been related to cognition during anaesthesia, but there are
      no detailed studies using median nerve somatosensory evoked responses (MnSSER).
      METHODS: We studied 49 patients during recovery from general anaesthesia
      (isoflurane/nitrous oxide or propofol) to assess implicit and explicit memory
      function in relation to mid-latency MnSSER. The MnSSER recordings were made
      before anaesthesia, during steady-state anaesthesia, and at the end of the
      recovery period. The patients were interviewed 24 h later about their memory for
      the immediate wake up phase. Statistical analysis was by multivariate analysis of
      variance. RESULTS: Out of 49 patients, 23 recalled the recovery period, 11 had
      implicit memory for an object shown to them during the recovery period, and 15
      did not have any memory for the recovery period. At RECOVERY the patients with
      recall had significantly shorter MnSSER latencies N45 and P50 and inter-wave
      conduction times LatN35-LatP45 than patients without memory (P<0.05).
      CONCLUSIONS: We conclude that MnSSER components warrant further investigation for
      studying the effects of anaesthetic drugs on cognitive function.

PMID- 11990268
TI  - Noise in the postanaesthesia care unit.
AB  - BACKGROUND: Although the postanaesthesia care unit (PACU) can be noisy, the
      effect of noise on patients recovering from anaesthesia is unknown. We studied
      the sources and intensity of noise in the PACU and assessed its effect on
      patients' comfort. METHODS: We measured noise in a five-bed PACU with a sound
      level meter. Noise levels were obtained using an A-weighted setting (dBA) and
      peak sound using a linear scale (dBL). Leq (average noise level at 5-s
      intervals), maximum Leq (LeqMax), minimum Leq (LeqMin) and noise peaks (Lpc) were
      calculated. During recording, an independent observer noted the origin of sounds
      from alarms and noise above 65 dB intensity (P65dB). Two hours after leaving the
      PACU, patients were asked about their experience and to rank their complaints on
      a visual analogue scale (VAS) using unstructured and structured questionnaires.
      RESULTS: We made 20,187 measurements over 1678 min. The mean Leq, LeqMax and
      LeqMin were 67.1 (SD 5.0), 75.7 (4.8) and 48.6 (4.1) dBA respectively. The mean
      Lpc was 126.2 (4.3) dBL. Five per cent of the noise was at a level above 65 dBA.
      Staff conversation caused 56% of sounds greater than 65 dB and other noise
      sources (alarm, telephone, nursing care) were each less than 10% of these sounds.
      Five patients reported disturbance from noise. There was no significant
      difference in Leq measured for patients who found the PACU noisy and those who
      did not [59.5 (3.1) and 59.4 (2.4) dBA respectively]. Stepwise multiple logistic
      regression indicated that only pain was associated with discomfort. CONCLUSIONS:
      Even though sound in the PACU exceeded the internationally recommended intensity
      (40 dBA), it did not cause discomfort. Conversation was the most common cause of
      excess noise.

PMID- 11990269
TI  - Remifentanil by patient-controlled analgesia compared with intramuscular
      meperidine for pain relief in labour.
AB  - BACKGROUND: The pharmacokinetics of remifentanil suggests that it may be suitable
      for analgesia during labour. METHODS: In an open pilot study, 36 women requesting
      meperidine for analgesia were recruited early in labour and randomized to receive
      either meperidine i.m. or remifentanil given as patient-controlled analgesia
      (PCA). Pain severity, sedation and anxiety were assessed with visual analogue
      scales and overall effective analgesia was assessed by the woman and midwife.
      RESULTS: The pain scores were lower in the remifentanil group: median pain score
      at 60 min was 72 mm for meperidine and 48 mm for remifentanil (P=0.004) and
      median maximum pain score during the first 2 h was 82.5 mm for the meperidine
      group and 66.5 mm for the remifentanil group (P=0.009). Both the midwives' and
      the women's assessments of overall effective analgesia were higher in the
      remifentanil group [Likert scale (5 = excellent to 1 = poor): chi2=12.10, P=0.002
      for mothers' assessment; chi2=12.80, P=0.002 for midwives' assessment].
      CONCLUSION: In this pilot study, remifentanil by PCA gave better pain relief to
      mothers in labour than intramuscular meperidine. However, remifentanil is a
      potent respiratory depressant and adequate continuous monitoring is necessary.

PMID- 11990270
TI  - Addition of meperidine to bupivacaine for spinal anaesthesia for Caesarean
      section.
AB  - BACKGROUND: In a prospective, randomized, double-blind, placebo-controlled trial,
      we investigated the effect of adding meperidine 10 mg to intrathecal bupivacaine
      on the duration of early postoperative analgesia in 40 patients having elective
      Caesarean section under spinal anaesthesia. METHODS: Patients received
      intrathecal injection of 0.5% hyperbaric bupivacaine 2.0 ml plus either normal
      saline 0.2 ml (saline group) or 5% meperidine 0.2 ml (meperidine group). After
      operation, all patients were given i.v. patient-controlled analgesia using
      morphine. RESULTS: The duration of effective analgesia, defined as the time from
      intrathecal injection to first patient-controlled analgesia demand, was greater
      in the meperidine group (mean 234 min, 95% confidence interval 200-269 min)
      compared with the saline group (mean 125 min, 95% confidence interval 111-138
      min; P<0.001). The 24 h morphine requirement was similar in the two groups. The
      meperidine group had a greater incidence of intraoperative nausea or vomiting
      compared with the saline group (11 vs 3; P=0.02). CONCLUSION: Addition of
      meperidine 10 mg to intrathecal bupivacaine for Caesarean section is associated
      with prolonged postoperative analgesia but with greater intraoperative nausea and
      vomiting.

PMID- 11990271
TI  - Abdominal pressure during laparoscopy: effects of fentanyl.
AB  - BACKGROUND: In patients breathing spontaneously during anaesthesia, expiration is
      active and opioids enhance this effect. The mechanical consequences are not well
      characterized. METHODS: We studied 14 patients undergoing laparoscopy for minor
      gynaecological procedures, anaesthetized with isoflurane in nitrous oxide, and
      breathing spontaneously through a laryngeal mask airway. We made direct
      recordings of intra-abdominal pressure and respiratory flow before and after
      giving fentanyl 25 microg i.v. RESULTS: Satisfactory records were obtained in 11
      patients. Before fentanyl, the abdominal pressure changes were small and had an
      inconsistent pattern, increasing in inspiration in seven patients and during
      expiration in five. After fentanyl, an increase in pressure during inspiration
      was seen in only two patients, and the intra-abdominal pressure during expiration
      was increased. The mean value of maximum abdominal pressure (which always
      occurred during expiration) increased from 17 (SD 5) cm H2O before to 25 (9) cm
      H2O after fentanyl (P<0.01). CONCLUSIONS: Direct measurements support previous
      findings that opioids stimulate active phasic expiratory activity and can cause
      large increases in abdominal pressure.

PMID- 11990272
TI  - Phonomyography of the corrugator supercilii muscle: signal characteristics, best
      recording site and comparison with acceleromyography.
AB  - BACKGROUND: This study investigated the acoustic signal characteristics and best
      recording site of phonomyography at the corrugator supercilii muscle and compared
      phonomyography with acceleromyography. METHODS: In 12 patients (group I), after
      induction of anaesthesia and insertion of a laryngeal mask, a microphone
      (frequency range 2.5 Hz to 10 kHz) was placed on six different areas on the
      forehead and the peak-to-peak response after single-twitch stimulation of the
      facial nerve was measured. The microphone was placed where the response was
      largest and mivacurium 0.2 mg kg(-1) was administered. Fast Fourier
      transformation was applied to all signals to determine peak frequencies and the
      power-frequency relationship at different stages of neuromuscular block. In an
      additional 15 patients (group II), the same microphone and an acceleromyographic
      probe were placed above the middle portion of the left and right eyebrows
      respectively. Onset and offset of neuromuscular block were determined after
      mivacurium 0.2 mg kg(-1). RESULTS: In all seven women and all five men in group
      I, the best response was obtained just above the middle portion of the eyebrow.
      Peak frequency was 4.1 (SD 0.9) Hz without neuromuscular block and did not change
      significantly during onset and offset of neuromuscular block. Ninety per cent of
      the total signal power was below 40 Hz. In group II, mean onset time and maximum
      effect measured were 104 (20) s and 76 (10)% respectively using acceleromyography
      and 134 (30) s and 92 (4)% using phonomyography (P<0.04). Mean time to reach 25,
      75 and 90% of control was 9.5 (2.8), 14 (5.1) and 15.1 (5.3) min respectively
      using acceleromyography and 6.9 (2.8), 12.5 (5.9) and 13.6 (4.9) min using
      phonomyography (P<0.04). Bland-Altman testing revealed significant bias
      (precision) for onset time, maximum effect and time to reach 25% of control
      (acceleromyography minus phonomyography) at -30 (38) s, -16 (11)% and 2.6 (2.8)
      min respectively. CONCLUSIONS: Phonomyography can be used to determine
      neuromuscular block at the corrugator supercilii muscle. In comparison with
      acceleromyography, phonomyography tends to measure a longer onset with more
      pronounced maximum effect and shorter recovery of neuromuscular block.

PMID- 11990273
TI  - Effect of different pulses of nitric oxide on venous admixture in the
      anaesthetized horse.
AB  - BACKGROUND: Dependent atelectatic lung areas open towards the end of inspiration
      when the lung opening pressure increases, and recollapse during expiration. We
      hypothesized that inhaled nitric oxide (NO) counteracts hypoxic vasoconstriction
      in these collapsing lung areas, resulting in increased pulmonary shunt perfusion.
      METHODS: We administered NO as a pulse and varied the pulse timing during
      inspiration in equine anaesthesia, where atelectasis develops regularly. Six
      spontaneously breathing standard breed trotters were studied under isoflurane
      anaesthesia in lateral recumbency. NO pulsed into the first 30% of inspiration
      (group NOp1) was assumed to affect open lung areas. To cover more open lung areas
      NO was then pulsed into the first 60% of inspiration (group NOp2). In a third
      group, administration between 50 and 80% of inspiration was aimed at the
      intermittently opening lung areas (group NOp3). RESULTS: With NOp1, venous
      admixture decreased by 8 (2)% (mean (SEM), P=0.045) and with NOp2 by 10 (1)%
      (P=0.01). With NOp3, venous admixture reduction was insignificant. CONCLUSIONS:
      Pulsed administration of NO in early inspiration is optimal in reducing right to
      left vascular shunt in atelectatic equine lung. This reduction is positively
      correlated with the magnitude of the initial shunt. With administration in early
      inspiration, NO is mostly taken up by the lung. This prevents NO accumulation and
      NO2 formation in rebreathing circuits. These findings may be important in humans
      when atelectasis occurs increasingly with overweight and age during anaesthesia,
      but also in postoperative intensive care and in ARDS.

PMID- 11990274
TI  - Role of nitric oxide and cyclooxygenase pathways in the coronary vascular effects
      of halothane, isoflurane and desflurane in red blood cell-perfused isolated
      rabbit hearts.
AB  - BACKGROUND: The coronary vascular endothelium could mediate some of the coronary
      effects of halogenated anaesthetic agents. The role of the endothelial
      vasodilator substances nitric oxide (NO) and prostaglandins (PGs) in the coronary
      effects of halothane and isoflurane remains to be determined and has not been
      investigated for desflurane. In this study, the roles of NO and cyclooxygenase
      pathways in the coronary effects of halothane, isoflurane and desflurane were
      studied in isolated red blood cell-perfused rabbit hearts. METHODS: Rabbit hearts
      were perfused by a Langendorf technique with red blood cells mixed with modified
      Krebs-Henseleit buffer. Coronary blood flow (CBF), oxygen consumption and
      myocardial performance were evaluated during exposure to 0.5, 1 and 2 rabbit
      minimum alveolar concentrations of halothane, desflurane and isoflurane.
      Thereafter, the same protocol was applied with the addition of N(G)-nitro-L
      arginine (L-NNA), indomethacin or a combination of both inhibitors. RESULTS:
      Similar and significant increases in CBF were observed with increasing
      concentrations of isoflurane and desflurane. In contrast, CBF did not change with
      halothane. The combination of the two antagonists abolished desflurane-induced
      vasodilation, whereas it did not change the isoflurane-mediated increase in CBF.
      Halothane-induced vasoconstriction was observed in the presence of a combination
      of indomethacin with L-NNA. CONCLUSIONS: Halothane and desflurane induce the
      release of vasodilating prostaglandins and NO in rabbit coronary arteries. In
      contrast, these mediators are not involved in the coronary vasodilating
      properties of isoflurane.

PMID- 11990275
TI  - Inhaled olprinone improves contractility of fatigued canine diaphragm.
AB  - BACKGROUND: Diaphragmatic fatigue is implicated as a cause of respiratory
      failure. This study was undertaken to evaluate the effects of inhaled olprinone,
      a newly developed phosphodiesterase III inhibitor, on the contractility of
      fatigued diaphragm in dogs. METHODS: Diaphragmatic fatigue was induced by
      intermittent supramaximal bilateral electrophrenic stimulation at a frequency of
      20 Hz stimulation applied for 30 min. When fatigue was established, group I (n=8)
      received inhaled vehicle; group II (n=8) received inhaled olprinone 1 mg; group
      III (n=8) received inhaled olprinone 2 mg. Diaphragmatic contractility was
      assessed by transdiaphragmatic pressure (Pdi, cm H2O). RESULTS: In the presence
      of fatigue, in each group, Pdi at low-frequency (20 Hz) stimulation decreased
      from baseline values (P<0.05), whereas Pdi at high-frequency (100 Hz) stimulation
      did not change. In groups II and III, during olprinone administration, Pdi at
      both stimuli increased from fatigued values (20 Hz stimulation: group II (mean
      (SD)) 10.8 (1.0) to 12.5 (1.3), group III 10.9 (1.7) to 15.0 (3.0); 100 Hz
      stimulation: group II 20.1 (1.9) to 22.6 (1.3), group III 20.6 (2.0) to 24.5
      (2.0), P<0.05). The increase in Pdi was larger in group III than in group II
      (P<0.05). CONCLUSIONS: Inhaled olprinone produces a dose-dependent improvement in
      contractility of fatigued canine diaphragm.

PMID- 11990276
TI  - Effects of propofol on lactate accumulation and oedema formation in focal
      cerebral ischaemia in hyperglycaemic rats.
AB  - BACKGROUND: In cerebral ischaemia, hyperglycaemia brings about severe lactate
      accumulation and neuronal damage when compared with normoglycaemia. Propofol has
      been known to suppress glucose metabolism in the brain and possess
      neuroprotective properties in cerebral ischaemia. Therefore, in this study we
      examined if propofol could attenuate lactate accumulation and neuronal damage in
      cerebral ischaemia under hyperglycaemic conditions. METHODS: Ten male wistar rats
      were divided into two experimental groups: low-dose (approximately 12 mg kg(-1)
      h(-1)) and high-dose (approximately 60 mg kg(-1) h(-1)) propofol groups (n=5 for
      each). Following injection of 2 g kg(-1) glucose intraperitoneally, the middle
      cerebral artery was occluded for 1 h, and then reperfused for the following 2 h.
      Lactate accumulation and oedema formation were estimated consecutively using
      nuclear magnetic resonance (NMR) techniques. RESULTS: Lactate accumulation and
      oedema formation increased continuously during ischaemia and reperfusion in the
      low-dose propofol group, which was attenuated in the high-dose propofol group.
      Lactate/NAA (N-acetylaspartate) ratio (as an index of lactate accumulation) 60
      and 120 min after reperfusion were 2.67 and 3.26 in low-dose group and 0.30 and
      0.10 in high-dose group. For NMR images the number of pixels with a low average
      diffusion coefficient (an index of the oedema formation), 60 and 120 min after
      reperfusion were 250.0 and 317.8 in low-dose group, and 16.0 and 12.4 in high
      dose group. CONCLUSION: High-dose propofol attenuated lactate accumulation and
      oedema formation in cerebral ischaemia in hyperglycaemic rats.

PMID- 11990277
TI  - The role of non-technical skills in anaesthesia: a review of current literature.

PMID- 11990278
TI  - Effects of remifentanil and alfentanil on the cardiovascular responses to
      induction of anaesthesia and tracheal intubation in the elderly.
AB  - BACKGROUND: We compared the effects of remifentanil and alfentanil on arterial
      pressure and heart rate at induction of anaesthesia and tracheal intubation in 40
      ASA I-III patients aged greater than 65 yr, in a randomized double-blind study.
      METHODS: Patients received either remifentanil 0.5 microg kg(-1) over 30 s,
      followed by an infusion of 0.1 microg kg min(-1) (group R) or alfentanil 10
      microg kg(-1) over 30 s, followed by an infusion of saline (group A). Anaesthesia
      was then induced with propofol, rocuronium, and 1% isoflurane with 66% nitrous
      oxide in oxygen. RESULTS: Systolic arterial pressure (SAP) and mean arterial
      pressure (MAP) decreased after the induction of anaesthesia (P<0.05) and
      increased for 3 min after intubation in both groups (P<0.05), but remained below
      baseline values throughout. Heart rate remained stable after induction of
      anaesthesia but increased significantly from baseline after intubation for 1 and
      4 min in groups R and A, respectively (P<0.05). There were no significant between
      group differences in SAP, MAP, and heart rate. Diastolic pressure was
      significantly higher in group A than group R at 4 and 5 min after intubation
      (P<0.05). Hypotension (SAP < 100 mm Hg) occurred in four patients in group R and
      three patients in group A. CONCLUSIONS: Remifentanil and alfentanil similarly
      attenuate the pressor response to laryngoscopy and intubation, but the incidence
      of hypotension confirms that both drugs should be used with caution in elderly
      patients.

PMID- 11990279
TI  - Management of life-threatening autonomic hyper-reflexia using magnesium sulphate
      in a patient with a high spinal cord injury in the intensive care unit.
AB  - We report the successful use of i.v. magnesium sulphate to control life
      threatening autonomic hyper-reflexia associated with chronic spinal cord injury
      in the intensive care environment. A 37-yr-old, male was admitted to the
      intensive care unit with a diagnosis of septic shock and acute renal failure
      secondary to pyelonephritis. He had been found unresponsive at home following a 2
      day history of pyrexia and purulent discharge from his suprapubic catheter. He
      had sustained a T5 spinal cord transection 20 yr previously. Initial management
      included assisted ventilation, fluid resuscitation, vasopressor support, and
      continuous veno-venous haemofiltration. The sepsis was treated with antibiotic
      therapy and percutaneous nephrostomy drainage of the pyonephrosis. On the fifth
      day, the patient developed profuse diarrhoea. This was associated with paroxysms
      of systemic hypertension and diaphoresis, his arterial pressure rising on
      occasion to 240/140 mm Hg. A diagnosis of autonomic hyper-reflexia was made and a
      bolus dose of magnesium sulphate 5 g was administered over 15 min followed by an
      infusion of 1-2 g h(-1). There was an almost immediate decrease in the severity
      and frequency of the hypertensive episodes. There were no adverse cardiac effects
      associated with the administration of magnesium, only a slight decrease in minute
      ventilation as the plasma level approached the upper end of the therapeutic range
      (2-4 mmol litre(-1)). In view of the beneficial effects observed in this case we
      advocate further research into the use of magnesium sulphate in the treatment or
      prevention of autonomic hyper-reflexia secondary to chronic spinal cord injury in
      the intensive care unit.

PMID- 11990280
TI  - Lumbar ependymoma presenting with paraplegia following attempted spinal
      anaesthesia.
AB  - Neurological deterioration from intraspinal haematoma following insertion of a
      spinal needle is extremely rare. We present the case of a 28-yr-old female, who
      presented with complete paraplegia following attempted spinal anaesthesia for
      delivery of her third child. Space-occupying iatrogenic spinal haemorrhage from a
      previously undiagnosed lumbar ependymoma was found to be the precipitating cause.
      Following laminotomy with blood clot and tumour removal her neurological function
      improved.

PMID- 11990281
TI  - Intraoperative pulmonary oedema in a child following systemic absorption of
      phenylephrine eyedrops.
AB  - Ophthalmic surgeons often apply phenylephrine topically to effect pupillary
      dilatation. We describe a paediatric patient in whom cardiac arrhythmias, severe
      hypertension and pulmonary oedema occurred following intraoperative ocular
      phenylephrine administration. We believe that systemic absorption of the drug was
      responsible and discuss ways in which this might be reduced when ocular
      phenylephrine is used in this context.

PMID- 11990282
TI  - Value of bispectral index monitoring during cardiopulmonary resuscitation.
AB  - A 67-yr-old man, undergoing pulmonary metastasis resection, experienced a
      postoperative cardiopulmonary arrest as a result of severe bleeding.
      Cardiopulmonary resuscitation (CPR) was initiated, then bispectral index (BIS)
      monitoring was used which reassured the medical team of the adequacy of the
      resuscitation.

PMID- 11990283
TI  - The British Journal of Anaesthesia. An informal history of the first 25 years.
AB  - In 1961, some 7 months after starting anaesthesia in the Leeds General Infirmary,
      I took out a subscription to the British Journal of Anaesthesia. It cost Pound
      Sterling3.15s.0d (Pound Sterling3.75) a year. The publishers John Sherratt and
      Son of Altringham) sent me the back numbers from the start of that year. I first
      had a paper published in the journal in 1965; first refereed a paper in 1969;
      joined the editorial board in 1975; and lasted there until 1998. The following
      account of the early years of the journal derives from the journal itself, and
      from records, letters and minutes of meetings kindly given to me by Dr Edmund
      Riding and Professor Andrew Hunter when they demitted offices with the journal.
      The history cannot be complete. Sadly, the earliest minutes books are lost. But
      there is much of interest covering the times when anaesthesia developed from the
      rag-and-bottle inhalation era to the use of intravenous anaesthetics,
      neuromuscular blocking agents, ventilators and monitoring. Thoracic and
      neurosurgical anaesthesia were revolutionized; cardiac surgery became possible;
      and resuscitation with intravenous fluids, blood and plasma all developed.
      Antibiotics improved care. Anaesthetists pioneered intensive care and latterly
      extended their roles in pain relief outside the operating theatre. All these
      developments have appeared in papers at some time in this journal. This is a
      personal view of the journal over its first 25 years: there will be errors and
      misinterpretations--these are mine.

PMID- 11990284
TI  - Air flow resistance of wet breathing system filters.

PMID- 11990285
TI  - Is xenon uptake in animals higher than reported previously?

PMID- 11990286
TI  - Measuring the cost of inhaled anaesthetics.

PMID- 11990287
TI  - Dexmedetomidine may be effective, but is it safe?

PMID- 11990288
TI  - Remifentanil and pain relief in labour.

PMID- 11990289
TI  - Remifentanil and pain relief in labour.

PMID- 11990290
TI  - Tracheal cuff pressure--a survey of clinical practice.

PMID- 11990291
TI  - Simple height-based method of choosing the correct tracheal tube size in
      children.

PMID- 11990292
TI  - Evaluation of the Greenbaum sub-tenon's block: a role in anticoagulated patients
      presenting for cataract surgery.

PMID- 11990293
TI  - Mobile operating theatre in a district general hospital.

PMID- 11990294
TI  - Salim and Mahmood modification of RAE tubes.

PMID- 11990295
TI  - Functional properties of EGFP-tagged skeletal muscle calcium-release channel
      (ryanodine receptor) expressed in COS-7 cells: sensitivity to caffeine and 4
      chloro-m-cresol.
AB  - We constructed and expressed in COS-7 cells, three E-green fluorescent protein
      (EGFP) tagged recombinant skeletal muscle ryanodine receptors (RYR). EGFP was
      tagged to (i) the NH2-terminus (nEGFP-RYR(FL)) and to (ii) the COOH-terminus
      (cRYR(FL)-EGFP) of the full length RYR; we also tagged the EGFP to (iii) the NH2
      terminus of a truncated version of the RYR (nEGFP-RYR(Bhat)) lacking the bulk of
      the protein. The fluorescent pattern EGFP with all three constructs colocalize
      with that of an endoplasmic reticulum (ER) membrane tracker fluorescent dye,
      indicating that the RYR constructs are targeted to ER membranes. Our results show
      that: (i) COOH-terminal tagging abolishes the sensitivity of the RYR to caffeine,
      whereas the presence of EGFP at the NH2-terminus does not affect caffeine
      sensitivity and (ii) 4-Cl-m-cresol sensitivity is lost both with the truncated
      nEGFP-RYR(Bhat) and the nEGFP-RYR(FL), while COOH-terminal tagging does not
      affect sensitivity to 4-chloro-m-cresol. The dose-response curves of caffeine
      induced calcium release of nEGFP-RYR(FL) differ from those of the truncated nEGFP
      RYR(Bhat). Maximal calcium release was approached at 10 mM caffeine with the
      nEGFP-RYR(FL), while cells expressing the nEGFP-RYR(Bhat) construct displayed a
      bell shaped curve and the maximal concentration for caffeine-induced calcium
      release was 5 mM. Equilibrium [3H]-ryanodine binding confirmed the calcium
      photometry data. Our results demonstrate that EGFP tagging modifies the
      pharmacological properties of RYR, and suggest that 4-chloro-m-cresol and
      caffeine act through different mechanisms and probably interact with different
      sites on the RYR calcium release channel.

PMID- 11990296
TI  - Monoclonal antibodies recognizing epitopes of calretinins: dependence on Ca2+
      binding status and differences in antigen accessibility in colon cancer cells.
AB  - Monoclonal antibodies are very helpful tools to investigate the localization and
      sometimes even the function of specific proteins in cells and tissues. By
      generating monoclonal antibodies against calretinin-22k (CR-22k), a C-terminally
      truncated isoform of calretinin (CR) as a result of alternative splicing of the
      CR mRNA, we envisaged that screening multiple monoclonal antibodies would allow
      the identification of CR-22k as well as CR. Both proteins share the first 178
      amino acids, but have different C-termini. All three antibodies 10C10, 6B3 and
      2H4 recognize recombinant CR-22k and the specificity to also recognize CR was
      demonstrated in brain extracts of different species and human tumour cells, which
      express CR. All monoclonal antibodies did not crossreact with the closely related
      protein calbindin D-28k. Antibody binding was depending on the Ca2+-binding
      status of both forms of calretinin. Generally, the Ca2+-bound form was better
      recognized than the Ca2+-free form. Carboxy- and amino-terminally truncated CR
      proteins were expressed in E. coli in order to characterize the epitopes
      recognized by the three antibodies. Additionally, tryptic and cyanogen bromide
      fragments were produced to further narrow down the sequences recognized by the
      three antibodies. 10C10 recognizes an epitope consisting of the linker region
      between EF-hand domains I and II and the N-terminal part of EF-hand II, while the
      others (6B3, 2H4) bind to a region including the linker between EF-hand domains
      III and IV. These antibodies are valuable tools to further investigate the
      distribution and eventually the specific function of these two proteins in the
      nervous tissue and under pathological conditions, e.g. in colon tumours and
      mesotheliomas.

PMID- 11990297
TI  - A ratiometric imaging method for mapping ion flux densities.
AB  - A heterogeneous distribution of ion channels on the cell surface is a
      prerequisite for several cellular functions. Thus, there has been considerable
      interest in methods allowing the mapping of ion channel distributions. Here we
      report on a novel ratiometric imaging technique appropriate to measure spatially
      resolved ion flux signals by using ion sensitive dyes. However, given that
      certain relevant cell properties like the surface to volume ratio may exhibit
      significant spatial heterogeneities, the local influx signal cannot be
      interpreted as a measure of the local open channel concentration or flux density.
      To overcome this problem, we suggest an internal normalization procedure, which,
      in analogy to, but clearly distinct from, well-established ratioing techniques,
      eliminates effects which would otherwise obscure the desired result. Ratioing is
      performed on flux signals from a given cell, triggered by two different,
      subsequent stimuli. If the two stimuli address different ion channels, the flux
      density distribution caused by two channel types can be determined relative to
      each other. In cases where one of the stimuli triggers a spatially homogeneous
      flux signal, ratioing yields an ion flux density map for a given channel type.
      Thus distribution patterns of ion channels active during a given stimulus may be
      derived.

PMID- 11990298
TI  - Na+-Ca2+ exchange activity in rat skeletal myotubes: effect of lithium ions.
AB  - The whole-cell patch-clamp technique coupled with intracellular [Ca2+]
      measurements was used to investigate the sodium-calcium exchange mechanism in rat
      skeletal muscle cells in primary culture. Replacing external Na+ ions with Li+ or
      N-methyl-D-glucamine (NMDG+) ions generated outward currents which were
      correlated with significant increases of free cytosolic-calcium concentration.
      These results strongly argue for a functional Na+-Ca2+ exchange mechanism working
      in its reverse mode. Moreover, the outward currents were sensitive to the new
      compound KB-R7943 (10 microM), which has been shown to be a potent inhibitor of
      the sodium-calcium exchanger. Outward Na+-Ca2+ exchange current densities were
      reduced in the presence of external Li+ as compared to those measured in the
      presence of NMDG+. After replacing internal sodium by lithium ions, rapid changes
      of external lithium concentrations generated sarcolemmal currents which were
      accompanied by subsequent variations of intracellular calcium activity. The
      currents were dependent on extracellular Li+ with a half-maximal activation at 67
      mM and a Hill coefficient of 2.9. This work shows that the Na+-Ca2+ exchanger is
      able to significantly influence the myoplasmic calcium concentration of cultured
      rat myotubes. On the other hand, our results suggest that Li+ ions may substitute
      Na+ ions to catalyse an electrogenic Li+/Ca2+ counter transport.

PMID- 11990299
TI  - Curcumin: a new cell-permeant inhibitor of the inositol 1,4,5-trisphosphate
      receptor.
AB  - Curcumin (diferuoylmethane or 1,7-bis (4-hydroxy-3-methoxyphenol)-1,6-hepatadiene
      3,5-dione) is the active ingredient of the spice turmeric. Curcumin has been
      shown to have a number of pharmacological and therapeutic uses. This study shows
      that curcumin is a potent inhibitor of the inositol 1,4,5-trisphosphate-sensitive
      Ca2+ channel (InsP3 receptor). In porcine cerebellar microsomes, the extent of
      InsP3-induced Ca2+ release (IICR) is almost completely inhibited by 50 microM
      curcumin (IC50 = 10 microM). As the extent of IICR cannot be restored back to
      control levels by the addition of excess InsP3 and since it has little effect on
      [3H]InsP3 binding to cerebellar microsomes, this inhibition is likely to be non
      competitive in nature. IICR in cerebellar microsomes is biphasic consisting of a
      fast and slow component. The rate constants for the two components are both
      reduced by curcumin to similar extents (by about 70% of control values at 40
      microM curcumin). In addition, curcumin also reduces agonist (ATP)-stimulated
      Ca2+ mobilization from intact HL-60 cells, indicating that curcumin is cell
      permeant. However, since it also affects intracellular Ca2+ pumps and possibly
      ryanodine receptors, it may lead to complex Ca2+ transient responses within
      cells, which may well explain some of its putative therapeutic properties.

PMID- 11990300
TI  - The American Society of Pediatric Hematology/Oncology Distinguished Career Award
      goes to Jeanne Lusher, M.D.

PMID- 11990301
TI  - From where do clinical trials come?

PMID- 11990302
TI  - A pharmacoeconomic analysis of pegaspargase versus native Escherichia coli L
      asparaginase for the treatment of children with standard-risk, acute
      lymphoblastic leukemia: the Children's Cancer Group study (CCG-1962).
AB  - PURPOSE: The purpose of this pharmacoeconomic analysis was to compare
      pegaspargase. a newer chemotherapeutic agent used for treating acute
      lymphoblastic leukemia, with native Escherichia coli L-asparaginase in induction,
      delayed intensification 1 and delayed intensification 2. MATERIALS AND METHODS: A
      subset of patients with newly diagnosed, standard-risk, acute lymphoblastic
      leukemia enrolled in the Children's Cancer Group (CCG) study CCG-1962 at seven
      participating institutions gave consent and was enrolled in our pharmacoeconomic
      analysis study. Societal (transportation, lodging, missed workdays, food,
      babysitter) and payer (frequency of encounters) cost data were collected from
      diaries (n = 27). Additional payer costs, such as drug costs, cost per clinic
      visit, and cost per inpatient day stay were collected from patients in CCG-1962
      and participating institutions. We considered costs of therapy, including higher
      pegaspargase costs when comparing regimens of pegaspargase versus native E. coli
      L-asparaginase in induction, delayed intensification 1, and delayed
      intensification 2. RESULTS: Our results showed that the costs of the two
      therapies were similar from the payer perspective, with pegaspargase costing 1.8%
      more than E. coli L-asparaginase. The difference between groups also was small
      (<1%) from the societal perspective. Inpatient stay accounted for 88% of
      pegaspargase payer costs and 91% of the native E. coli L-asparaginase costs.
      CONCLUSION: We recommend that pegaspargase not be withheld from treatment
      protocols solely because of its higher pharmacy costs.

PMID- 11990303
TI  - Intermediate-dose methotrexate and intravenous 6-mercaptopurine chemotherapy for
      children with acute lymphoblastic leukemia who did not respond to initial
      induction therapy.
AB  - PURPOSE: To determine the complete remission rate of children with acute
      lymphoblastic leukemia (ALL) who were not induced into remission by initial
      therapy, when subsequently treated with intermediate-dose methotrexate and
      intravenous 6-mercaptopurine. PATIENTS AND METHODS: Children with B-precursor ALL
      who did not achieve initial remission after 4 or 6 weeks of standard three- or
      four-drug induction chemotherapy were entered on study. Therapy consisted of
      three doses at weekly intervals of methotrexate 1,000 mg/m2 over 24 hours
      followed by 6-mercaptopurine 1,000 mg/m2 over 8 hours 20 minutes. Patients
      achieving a partial remission could receive two additional weekly courses of
      methotrexate and 6-mercaptopurine. Initially, patients received weekly
      intrathecal chemotherapy, but the study was amended to include intrathecal
      therapy only at week 1. RESULTS: Nineteen patients were entered on study. All
      were evaluable for toxicity and response. There were seven complete remissions,
      four partial remissions, six patients with no response, and two children with
      progressive disease, for an overall complete remission rate of 37%. One patient
      was removed from the study after the second course of methotrexate and 6
      mercaptopurine because of renal failure. Two patients had neurologic toxicity
      resulting in a study amendment. No patients subsequently experienced neurologic
      toxicity. CONCLUSIONS: Intermediate-dose intravenous methotrexate and intravenous
      6-mercaptopurine can induce remission in some patients with ALL who experience
      initial induction failure. Features predicting complete remission, however, could
      not be identified.

PMID- 11990304
TI  - Use of amifostine in the therapy of osteosarcoma in children and adolescents.
AB  - Amifostine protects normal tissue from the cytotoxic damage induced by radiation
      and chemotherapy. In this study, 39 consecutive newly diagnosed children with
      osteosarcoma were assessed; 20 received amifostine and 19 did not. The
      chemotherapy regimen included an induction phase of three cycles of cisplatin
      (100 mg/m2), carboplatin (500 mg/m2), and doxorubicin (60 mg/m2), followed by
      surgery. Alternating cycles of cisplatin/ifosfamide (9 mg/m2),
      ifosfamide/doxorubicin, carboplatin/doxorubicin, and ifosfamide/carboplatin were
      administered every 3 weeks to complete 26 weeks of treatment. Amifostine was
      administered 15 minutes before the infusions of cisplatin and carboplatin in a
      total of 193 infusions. Side effects during infusions and renal, hearing, and
      bone marrow toxicities were evaluated and compared between the two groups.
      Hypotension was observed in 28 (14.5%) infusions. No patient required
      discontinuation of therapy. Fewer than two episodes of vomiting occurred in 130
      (71%) infusions and two to five episodes occurred in 51 (28%) infusions, and no
      patient had grade 4 toxicity. There was no difference between the two groups
      regarding renal toxicity (creatinine clearance). Neutropenia and leukopenia were
      significantly less frequent in the amifostine group. No difference was observed
      in platelet and hearing toxicities. Amifostine was well tolerated in doses of 740
      mg/m2 in children and adolescents, and myelotoxicity was less severe in the
      amifostine group. This was a pilot study for further evaluation in a larger
      randomized trial.

PMID- 11990305
TI  - Improved survival for patients with recurrent Wilms tumor: the experience at St.
      Jude Children's Research Hospital.
AB  - BACKGROUND: Reported estimates of survival for patients with recurrent Wilms
      tumor are 24% to 43%. Because published survival data are more than a decade old
      and do not reflect advances in therapy, the authors reviewed their experience in
      treating recurrent Wilms tumor to determine whether the probability of survival
      has increased. PATIENTS AND METHODS: The authors reviewed the cases of 54
      patients with recurrent Wilms tumor who were treated on one of six consecutive
      clinical trials at St. Jude Children's Research Hospital between 1969 and 2000.
      RESULTS: Five-year overall survival estimates after relapse were 63.6 +/- 15.7%
      for patients treated during or after 1984 (n = 20) and 20.6 +/- 6.5% for patients
      treated before 1984 (n = 34) (P = 0.002). When the analysis was restricted to
      patients with high-risk clinical features, 5-year overall survival estimates were
      47.6 +/- 15.7% for those treated in the modern era (n = 16) and 11.1 +/- 5.2% for
      those treated in the earlier era (n = 25) (P = 0.005). Only three patients
      received high-dose chemotherapy with autologous stem cell rescue; one survived.
      No patients with recurrent anaplastic histology disease survived. CONCLUSIONS:
      Significant progress has been achieved in the treatment of recurrent favorable
      histology Wilms tumor using multimodality salvage regimens with conventional
      doses of chemotherapy. Novel therapeutic strategies will be necessary to cure
      patients with recurrent anaplastic Wilms tumor.

PMID- 11990306
TI  - Meningiomas in children and adolescents.
AB  - PURPOSE: To review the diagnosis, treatment, and long-term outcome of children
      and adolescents with meningiomas diagnosed by a single institution and compare
      these findings with other published data. PATIENTS AND METHODS: A 25-year
      retrospective analysis of 18 patients with meningioma diagnosed at Children's
      Hospital Medical Center, Cincinnati, Ohio was performed. A literature review of
      published reports was undertaken to compare evaluation. treatment, and outcome
      for similar patients. RESULTS: Patients ranged from ages 19 months to 17 years at
      diagnosis. The most common symptoms were headache (5) and seizures (5), although
      most patients had multiple symptoms. The brain was the primary location of tumor
      in 17 patients, with the remaining tumor located in the spine. Comorbid diagnoses
      were common, including developmental delay, balanced chromosomal translocation,
      type I diabetes mellitus, neurofibromatosis, Klinefelter syndrome, and seizures.
      Eleven patients had gross total resection performed. Four patients had malignant
      meningiomas. Two patients were treated with radiotherapy only, one had
      chemotherapy only, and two underwent both. Karyotype abnormalities most commonly
      involved chromosome 22, but other abnormalities were present. Sixteen patients
      remain alive and two patients, having had malignant tumors, are dead of disease.
      Long-term sequelae include seizures, diabetes insipidus, blindness,
      neuropsychologic abnormalities, and multiple surgical procedures. Only three
      patients are self-described as being without problems. CONCLUSIONS: Based on this
      study and a literature review, the roles of surgery, radiation, and chemotherapy
      remain unclear. Long-term outcome for patients with meningiomas, especially as it
      relates to cognitive function, is rarely reported. This group of patients has a
      high incidence of morbidity associated not only with treatment but also with
      preexisting diseases. These data indicate the need for a national cooperative
      group study to better understand the evaluation, treatment, and outcome for
      children and adolescents who are treated for meningiomas.

PMID- 11990307
TI  - Genetic alterations in childhood medulloblastoma analyzed by comparative genomic
      hybridization.
AB  - Despite intensive therapy, the survival of children with medulloblastoma remains
      disappointing. Moreover, children who survive are affected by serious long-term
      sequelae of treatment that impair their quality of life. In search of chromosomal
      aberrations indicative of sites involved in oncogenic transformation and in an
      attempt to find reliable prognostic markers, the authors analyzed 15
      medulloblastomas by comparative genomic hybridization. All neoplasms showed
      chromosomal abnormalities. The most frequent losses were 17p (7/15 tumors), 8p
      and 11p (6/15), 10p, 1lq, 16q, and 20q (5/15), and 20p (4/15). Gains were
      recurrently found at 7q (10/15 tumors), 17q and 18q (9/15 tumors), 7p and 13q
      (7/15), 18p (6/15), and 1q, 4q, 6q. and 9p (5/15 tumors). Four tumors showed loss
      of 17p together with gain of 17q, suggesting an isochromosome 17q. High-level
      amplifications were seen at 1p34, 5p15, 13q34, and 18p11 (one tumor each), and at
      2p15 in two tumors, one of which was proven to be N-Myc amplification. The
      overall pattern of alterations found in this study confirms the findings of other
      studies and adds two novel regions with chromosomal gains, at 13q and 18q.
      Previous reports on the relation between 17q gain and survival could not be
      confirmed, whereas amplification of N-myc or L-myc seems to indicate poor
      clinical outcome.

PMID- 11990308
TI  - Hematologic findings associated with thrombocytopenia during the acute phase of
      exanthem subitum confirmed by primary human herpesvirus-6 infection.
AB  - PURPOSE: To elucidate the mechanism underlying thrombocytopenia during the acute
      phase of exanthem subitum (ES), the associated hematological findings were
      investigated. PATIENTS AND METHODS: Five infants with thrombocytopenia during the
      acute phase of ES serologically confirmed by primary human herpesvirus-6 (HHV-6)
      were examined and followed-up. RESULTS: Thrombocytopenia was accompanied by
      neutropenia, leukopenia, and decreased reticulocyte fraction during the acute
      phase. These changes were self-limiting, and the sequential changes of platelet,
      neutrophil count, and reticulocyte fraction were closely linked. Slight but
      significant decreases in hemoglobin in the convalescent phase and mild increases
      in atypical lymphocytes after subsidence of the fever were observed.
      Hemophagocytosis and increase in atypical lymphocytes in the bone marrow
      suggested that bone marrow cells were influenced by primary HHV-6 infection.
      Platelet-associated immunoglobulin G and indirect antiplatelet antibody were
      negative. Plasma levels of fibrinogen and D-dimer of fibrinogen degradation
      products were within normal ranges. CONCLUSIONS: Thrombocytopenia is a
      complication of ES, and this may result from bone marrow suppression rather than
      from immune-mediated peripheral consumption seen in acute idiopathic
      thrombocytopenic purpura or from disseminated intravascular coagulation.

PMID- 11990309
TI  - Allogeneic bone marrow transplantation in children with chronic myelogenous
      leukemia.
AB  - PURPOSE: To determine the outcome of children undergoing allogeneic bone marrow
      transplantation for chronic myelogenous leukemia (CML) at the authors'
      institution. PATIENTS AND METHODS: Between 1985 and 1999, 18 allogeneic bone
      marrow transplantations were performed in 17 patients with CML at the Hospital
      for Sick Children in Toronto. Median age at diagnosis was 9.5 years (range 3-17).
      Fourteen patients had disease in the first chronic phase, one had disease in the
      second chronic phase, and two had disease in the accelerated phase. Preparative
      regimens varied, with radiation-based protocols used in eight patients. Thirteen
      donors were related (11 matched, 2 mismatched); four were unrelated (2 matched, 2
      mismatched). Patients received T-cell-replete bone marrow a median of 7.5 months
      (range 2.2-22) from diagnosis. A median of 3.0 x 10(8)/kg nucleated cells was
      infused (range 1.6-6.7). Graft-versus-host disease (GVHD) prophylaxis consisted
      of cyclosporine and methotrexate in 13 children. cyclosporine in three, and
      methotrexate in one. RESULTS: Primary graft failure occurred in one patient.
      Grade 2 acute GVHD or more developed in 11 of the 17 children (64%; grade 2 in 4,
      grade 3 in 7). Chronic GVHD occurred in 6 of the 16 patients at risk (37.5%; 5
      extensive, 1 localized). No patient experienced overt or cytogenetic relapse.
      There were two deaths (12%): one from acute GVHD and cytomegalovirus pneumonia
      and the other from chronic GVHD. Probability of 5-year event-free survival was 87
      +/- 9%. CONCLUSIONS: These results strongly support the practice of
      allotransplantation in children with CML, even in the setting of advanced disease
      and histoincompatibility. Efforts should be aimed at reducing the transplantation
      related death rate.

PMID- 11990310
TI  - Immunotherapy with autologous dendritic cells and tumor-specific synthetic
      peptides for synovial sarcoma.
AB  - Synovial sarcoma in an 11-year-old Japanese girl relapsed 5 months after
      autologous stem cell transplantation. Autologous dendritic cells (DCs) were
      generated from her peripheral blood mononuclear cells using
      granulocyte/macrophage colony-stimulating factor and IL-4. Dendritic cells were
      pulsed with synthetic peptides containing a junctional region of SYT-SSX2 fusion
      protein generated by t(X;18) and were administered once per week. No side effects
      were observed. Growth of metastatic nodules in the lung was temporally
      suppressed. The delayed-type hypersensitivity responses in skin were enhanced to
      tumor lysate but not to peripheral blood mononuclear cell lysate. The CD3+ cells
      cultured with pulsed DCs lysed tumor cells in vitro. Immunotherapy using DCs and
      tumor-specific peptides may be a safe approach in the treatment of childhood
      cancer.

PMID- 11990311
TI  - Lineage-specific trisomy 21 in a neonate with resolving transient
      myeloproliferative syndrome.
AB  - The cellular events that lead to transient myeloproliferative syndrome (TMS) in
      patients with trisomy 21 mosaicism confined to the hematopoietic system are
      poorly understood. The authors attempt to define the event that led to the
      development of TMS in a single patient with clonal trisomy 21. A phenotypically
      normal neonate with clonal trisomy 21 is described. At the time when his TMS was
      resolving, fluorescent in situ hybridization analysis was performed on cell
      populations sorted by flow cytometry to determine what cell populations contained
      trisomic cells. Trisomy 21 was found in cells of the erythrocytic and monocytic
      lineages, but not in the stem cells, progenitor compartment, megakaryocytes,
      lymphocytes, or neutrophils. These results support the hypothesis that, in this
      neonate, trisomy 21 occurred in a multipotent hematopoietic progenitor, and a
      subsequent event led to the appearance of the blast population.

PMID- 11990312
TI  - Association of prolonged fever and hypernatremia: rare presentation of
      hypothalamic/third ventricle tumor in a toddler.
AB  - The authors describe a 2-year-old boy with a clinical presentation of prolonged
      fever of unknown origin and severe hypernatremia. This rare association was the
      result of a hypothalamic/third ventricle tumor. The lesion was removed and was
      found to be a low-grade neuronal tumor. After surgery, the child did generally
      well, but hypothalamic thermoregulatory and osmoregulatory functions were not
      restored. These presenting symptoms, their pathophysiology, and the implications
      for pediatric practice are discussed.

PMID- 11990313
TI  - Successful multimodality therapy of recurrent multifocal juvenile granulosa cell
      tumor of the ovary.
AB  - Juvenile granulosa cell tumor (JGCT) of the ovary, a rare pediatric cancer,
      carries a very poor prognosis in advanced and recurrent cases. A 10-year-old girl
      with stage IA JGCT, initially treated with resection only, presented with
      extensive unresectable multifocal pelvic recurrence. She underwent surgery,
      chemotherapy (cisplatin/paclitaxel alternating with
      cisplatin/cyclophosphamide/etoposide/bleomycin), myeloablative chemotherapy
      (carboplatin/etoposide/melphalan) with autologous bone marrow transplant, and
      pelvic radiation. She tolerated therapy well and is in complete remission 69
      months after her recurrence.

PMID- 11990314
TI  - Congenital erythrocytosis with increased erythropoietin level.
AB  - The term "absolute erythrocytosis" denotes a heterogeneous group of disorders
      characterized by an increased red blood cell mass. The authors describe a 20
      month-old girl with absolute erythrocytosis. Erythropoietin levels were found to
      be extremely increased, although extensive evaluation failed to reveal a cause
      for such an inappropriate increase. Of interest is also the documentation of
      spontaneous erythroid colony formation in the patient's bone marrow cultures.
      Although such a finding is considered typical of polycythemia vera, the
      diagnostic criteria of this myeloproliferative disorder were not met.

PMID- 11990315
TI  - Candida dubliniensis fungemia and vascular access infection.
AB  - Candida dubliniensis is a newly recognized species of yeast, which may have been
      forrmerly identified as Candida albicans, that has been rarely isolated from
      invasive fungal infections among humans. The authors document a C. dubliniensis
      fungemia that occurred during the course of a vascular access infection in a 2
      year-old who was undergoing active therapy for neuroblastoma. Presumptive C.
      albicans isolates from an 18-year period were reassessed, and it was found that
      C. dubliniensis is a rare cause of fungemia among pediatric patients (0.5% of all
      such isolates).

PMID- 11990316
TI  - Bullous acral erythema secondary to high-dose methotrexate.

PMID- 11990317
TI  - Developmental-behavioral initiation of evolutionary change.
AB  - The traditional approach to evolutionary psychology relies entirely on natural
      selection as the cause of the evolution of adaptations. Exclusive reliance on
      natural selection overlooks the fact that changes in development are a necessary
      prerequisite for evolutionary change. These developmental changes provide the
      material for natural selection to work on. In the neo-Darwinian scenario, the
      mechanisms of evolution are mutation or genetic recombination, selection,
      migration, and eventual reproductive isolation. In the spirit of evolutionary
      pluralism, the author describes a different 3-stage scenario in which migration
      (the invasion of new niches or habitats) may occur without mutation or genetic
      recombination and selection first initiating a change in genes or gene
      frequencies.

PMID- 11990318
TI  - Consciousness and the varieties of emotion experience: a theoretical framework.
AB  - Data reviewed suggest that previous theories of emotion experience are too narrow
      in scope and that lack of consensus is due to the fact that emotion experience
      takes various forms and is heterogenous. The authors treat separately the content
      of emotion experience, the underlying nonconscious correspondences, and processes
      producing emotion experience. They classify the nature and content of emotion
      experience and propose that it depends on 3 aspects of attention: mode (analytic
      synthetic; detached-immersed), direction (self-world), and focus (evaluation
      action). The account is informed by a 2-level view of consciousness in which
      phenomenology (1st order) is distinguished from awareness (2nd order). These
      distinctions enable the authors to differentiate and account for cases of
      "unconscious" emotion, in which there is an apparent lack of phenomenology or
      awareness.

PMID- 11990319
TI  - Measuring and modeling the trajectory of visual spatial attention.
AB  - In a novel choice attention-gating paradigm, observers monitor a stream of 3 x 3
      letter arrays until a tonal cue directs them to report 1 row. Analyses of the
      particular arrays from which reported letters are chosen and of the joint
      probabilities of reporting pairs of letters are used to derive a theory of
      attention dynamics. An attention window opens 0.15 s following a cue to attend to
      a location, remains open (minimally) 0.2 s, and admits information simultaneously
      from all the newly attended locations. The window dynamics are independent of the
      distance moved. The theory accounts for about 90% of the variance from the over
      400 data points obtained from each of the observers in the 3 experiments reported
      here. With minor elaborations, it applies to all the principal paradigms used to
      study the dynamics of visual spatial attention.

PMID- 11990320
TI  - Decisions and the evolution of memory: multiple systems, multiple functions.
AB  - Memory evolved to supply useful, timely information to the organism's decision
      making systems. Therefore, decision rules, multiple memory systems, and the
      search engines that link them should have coevolved to mesh in a coadapted,
      functionally interlocking way. This adaptationist perspective suggested the scope
      hypothesis: When a generalization is retrieved from semantic memory, episodic
      memories that are inconsistent with it should be retrieved in tandem to place
      boundary conditions on the scope of the generalization. Using a priming paradigm
      and a decision task involving person memory, the authors tested and confirmed
      this hypothesis. The results support the view that priming is an evolved
      adaptation. They further show that dissociations between memory systems are not-
      and should not be--absolute: Independence exists for some tasks but not others.

PMID- 11990321
TI  - The production and perception of randomness.
AB  - This article contains a discussion of the elusive nature of the concept of
      randomness, a review of findings from experiments with randomness production and
      randomness perception tasks, and a presentation of theoretical treatments of
      people's randomization capabilities and limitations. The importance of task
      instructions and the difficulty of interpreting results when instructions are
      vague or ambiguous are stressed. The widely held view that people are incapable
      of generating or recognizing randomness is shown to lack the strong experimental
      support that has sometimes been claimed for it.

PMID- 11990322
TI  - False memories of the future: a critique of the applications of probabilistic
      reasoning to the study of cognitive processes.
AB  - The authors argue that the ways in which people-scientists and laymen-use
      probabilistic reasoning is predicated on a set of often questionable assumptions
      that are implicit and frequently go untested. They relate to the correspondence
      between the terms of a theory and the observations used to validate the theory
      and to the implicit understandings of intention and prior knowledge that arise
      between the conveyer and the receiver of information. The authors show several
      ways in which the use of probabilistic reasoning rests on a priori commitments to
      a partitioning of an outcome space and demonstrate that there are many more
      assumptions underlying the use of probabilistic reasoning than are usually
      acknowledged. They unfold these assumptions to show how several different
      interpretations of the same results in behavioral decision theory and cognitive
      psychology are equally well supported by "the facts." They then propose a more
      comprehensive approach to mapping cognitive processes than those currently used,
      one that is based on the analysis of all of the relevant alternative
      interpretations presented in the article.

PMID- 11990323
TI  - An instance theory of attention and memory.
AB  - An instance theory of attention and memory (ITAM) is presented that integrates
      formal theories of attention and memory phenomena by exploiting commonalities in
      their formal structure. The core idea in each theory is that performance depends
      on a choice process that can be modeled as a race between competing alternatives.
      Attention and categorization are viewed as different perspectives on the same
      race. Attention selects objects by categorizing them; objects are categorized by
      attending to them. ITAM incorporates each of its ancestors as a special case, so
      it inherits their successes.

PMID- 11990324
TI  - Theoretical and computational analysis of skill learning, repetition priming, and
      procedural memory.
AB  - This article analyzes the relationship between skill learning and repetition
      priming, 2 implicit memory phenomena. A number of reports have suggested that
      skill learning and repetition priming can be dissociated from each other and are
      therefore based on different mechanisms. The authors present a theoretical
      analysis showing that previous results cannot be regarded as evidence of a
      processing dissociation between skill learning and repetition priming. The
      authors also present a single-mechanism computational model that simulates a
      specific experimental task and exhibits both skill learning and repetition
      priming, as well as a number of apparent dissociations between these measures.
      These theoretical and computational analyses provide complementary evidence that
      skill learning and repetition priming are aspects of a single underlying
      mechanism that has the characteristics of procedural memory.

PMID- 11990325
TI  - Bioartificial liver support system: a "bridge" too far?

PMID- 11990326
TI  - Response to hepatitis B vaccine in preterm babies.
AB  - INTRODUCTION: A well-accepted vaccination schedule for preterm babies is not
      available. We therefore studied the response to hepatitis B vaccine in preterm
      babies. METHODS: 60 babies born to HBsAg-negative mothers were studied. Group I
      (n=20) consisted of term babies with birth weight >2.5 Kg, group II (n=20)
      included preterm babies with birth weight between 1.8 and 2.49 Kg, and group III
      (n=20) included preterm babies with birth weight between 1.2 and 1.79 Kg. Mean
      gestational age in the three groups was 38.5 (1.1), 33.5 (1.4) and 32.7 (2.1)
      weeks, respectively. All babies received 3 doses (10 microg/0.5 mL) of a
      recombinant HBV vaccine within 3 days of birth, and at 6 weeks and 6 months of
      life. Anti-HBs levels were measured one month after the 2nd and 3rd doses each;
      the immune response was categorized as good responders (anti-HBs >100 mIU/mL, low
      responders (anti-HBs 10-100 mIU/mL) and non-responders (anti-HBs <10 mIU/mL).
      RESULTS: Good antibody response after the second dose was seen in 95% of babies
      in group I, 60% of those in group II and 10% of those in group III. This
      increased to 100%, 90% and 45%, respectively after the third dose. The response
      was influenced by gestational age (r=0.73); 94% of babies with gestational age 34
      36 weeks attained good antibody response compared to only 55% of babies with
      gestational age of 31-33 weeks. Birth weight had no independent influence on the
      antibody response. CONCLUSION: The response to hepatitis B vaccine is influenced
      by gestational age. Hence, in preterm babies, it is advisable to check antibody
      titers one month after the third dose to assess the need for a booster dose.

PMID- 11990327
TI  - Thymosin alpha in the treatment of chronic hepatitis B: an uncontrolled open
      label trial.
AB  - BACKGROUND: Interferon treatment for chronic hepatitis B has low efficacy and is
      associated with serious side effects. It is therefore important to assess the
      role of other drugs in the treatment of this condition. AIMS: To assess the
      efficacy and safety of thymosin alpha in 20 patients with hepatitis B-related
      liver disease. METHODS: Patients with chronic hepatitis B, HBV DNA positivity,
      ALT more than 1.5 times the upper limit of normal and liver biopsy showing
      chronic hepatitis or cirrhosis were treated with thymosin alpha 1.6 mg
      subcutaneously twice a week for 6 months. Biochemical and serological markers
      were assessed pre-treatment, immediately post treatment, and 6 months and 1 year
      after end of treatment. RESULTS: Of 20 patients, 15 had chronic hepatitis and 5
      had cirrhosis on histology; 17 were HBeAg-positive and 3 were HBeAg-negative.
      Eight patients were interferon non-responders and 12 were naive patients. Four
      patients had end-of-treatment response and two additional patients had a delayed
      response within 6 months of treatment; one responder had a relapse within 1 year
      of treatment. Overall sustained response rate was 25% (5 of 20). No patient
      cleared HBsAg. Reduction in ALT levels was observed after treatment and persisted
      one year later. No significant side effects were observed. CONCLUSION: Thymosin
      alpha is a safe and effective alternative treatment modality in chronic hepatitis
      B.

PMID- 11990328
TI  - Pharmacokinetics of ciprofloxacin in patients with liver cirrhosis.
AB  - BACKGROUND: Bacterial infections are common in patients with cirrhosis of liver
      and are frequently treated with ciprofloxacin. Literature on pharmacokinetics of
      ciprofloxacin in patients with cirrhosis of the liver is scanty. The present
      study compared the pharmacokinetics of ciprofloxacin in cirrhotic patients with
      that in healthy volunteers. METHODS: In 20 patients with cirrhosis of liver (all
      Child-Pugh class B) and 10 healthy volunteers, plasma levels of ciprofloxacin
      were measured using high-performance liquid chromatography at several time points
      after a 500-mg oral dose. Various pharmacokinetic parameters were calculated.
      RESULTS: No significant differences were observed in maximum plasma levels
      reached (mean [SD] 2.6 [0.6] vs 2.6 [1.3] microg/ml), time taken for maximum
      plasma levels to be reached (1.3 [0.6] vs 1.5 [0.9] h), t1/2a (0.7 [0.3] vs 0.4
      [0.9] h), elimination half-life (3.6 [1.2] vs 3.2 [1.8] h), and area under the
      curve (19.3 [3.8] vs 21.9 [4.5] microg/mL x h) in healthy volunteers and
      cirrhotic patients, respectively. CONCLUSIONS: Pharmacokinetics of ciprofloxacin
      is unaltered in patients with liver cirrhosis. Ciprofloxacin can be safely
      administered in the usual doses in such patients.

PMID- 11990329
TI  - Clinico-pathological follow-up after total colectomy and straight ileo-anal
      anastomosis done for ulcerative colitis.
AB  - BACKGROUND: Restorative proctocolectomy is used as surgical treatment for
      ulcerative colitis. We have earlier documented adaptative changes in the terminal
      ileum after total colectomy, and straight ileo-anal anastomosis. AIM: To
      correlate the morphologic and functional changes in the ileal mucosa after total
      colectomy and hand-sewn straight ileo-anal anastomosis for ulcerative colitis.
      METHODS: Thirty consecutive patients (age range 15-50 years, 24 men) who had
      undergone total colectomy, rectal mucosectomy and hand-sewn straight ileo-anal
      anastomosis for ulcerative colitis were included in the study. These patients
      were followed up at 3-monthly intervals following surgery for two years and later
      once every year for a median duration of 9.5 (range 1-17) years. The clinical
      parameters studied were weight gain, frequency of stools, nature of stools,
      nocturnal stool frequency and need for antidiarrheal drugs. At each follow-up
      visit they were subjected to per rectal ileoscopy with ileal biopsy and barium
      enema. Ileal biopsy was analyzed histologically and histochemically. RESULTS: The
      clinical features improved over time, with average weight gain of 5 (range 1-7)
      Kg at one year. Frequency of stools decreased from 8-10 per day to 2-3 per day.
      The stools became semisolid and there was no need for antidiarrheal drug by the
      end of one year. All the patients showed adaptative changes in the ileum. The
      ileal mucosa was completely transformed into colonic type by the end of one year,
      colonoscopically (spacious lumen characteristic of colon), radiologically
      (disappearance of ileal characteristics with rectosigmoid-like appearance),
      histologically (blunting of villi with increase in goblet cells), and
      histochemically (sialomucin pattern to sulfomucin pattern). CONCLUSIONS: The
      ileum undergoes adaptative changes with corresponding improvement of clinical
      parameters over time, after proctocolectomy and ileoanal anastomosis for
      ulcerative colitis.

PMID- 11990330
TI  - Endoscopic treatment of chronic pancreatitis.
AB  - Endoscopic therapies, originally utilized for problems in the biliary tree, have
      been adapted for use in the pancreas. Despite widespread adoption and
      implementation of these techniques, there are few controlled studies comparing
      pancreatic endotherapy with either surgery or traditional medical treatment. This
      review attempts to summarize current endoscopic practice in treating the ductal
      obstructions and leaks associated with chronic pancreatitis and place these
      techniques into perspective with respect to alternative management strategies.

PMID- 11990331
TI  - Plummer Vinson syndrome: unusual features.
AB  - Plummer Vinson syndrome is a constellation of postcricoid esophageal webs, iron
      deficiency anemia, dysphagia and koilonychia. We describe some unusual
      manifestations in three patients with this syndrome; these were clubbing instead
      of koilonychia, tortuous esophagus in addition to presence of esophageal webs,
      and celiac disease.

PMID- 11990332
TI  - Esophago-gastric dissociation complicating devascularization procedure for portal
      hypertension.
AB  - Devascularization surgery for portal hypertension, indicated in selected
      patients, is considered safe. A 15-year-old boy with cirrhosis underwent elective
      modified Sugiura's devascularization procedure for secondary prophylaxis of
      variceal bleeding. He developed esophago-gastric dissociation, which was
      successfully managed with emergency feeding jejunostomy and restoration of gut
      continuity three months later.

PMID- 11990333
TI  - Spontaneous duodenal perforation in a newborn.
AB  - A full-term 4-day-old male baby presented with spontaneous duodenal perforation
      into the lesser sac. Exploration revealed a perforation in the posteromedial wall
      of the second portion of the duodenum. The perforation was closed and the baby
      recovered uneventfully.

PMID- 11990334
TI  - Primary choriocarcinoma of jejunum.
AB  - A 60-year-old man was admitted with pain in the abdomen and vomiting for one day;
      radiography revealed pneumoperitoneum. Laparotomy with excision of ulcer-bearing
      portion of the jejunum was done. Histology revealed choriocarcinoma with
      syncytiotrophoblastic and cytotrophoblastic cell differentiation.
      Postoperatively, urine and serum showed high levels of beta-human chorionic
      gonadotrophins. The patient expired after an unsatisfactory postoperative course.

PMID- 11990335
TI  - Recurrent inflammatory pseudotumor of small bowel mesentery presenting as
      perforative peritonitis.
AB  - A 62-year-old man with recurrent inflammatory pseudotumor of the small bowel
      mesentery presented with perforative peritonitis; such a presentation has not
      been reported. The mass was excised successfully.

PMID- 11990336
TI  - Degloving injury of small intestine.
AB  - Self-inflicted stab wounds are seldom very grave. We report a 25-year-old man who
      inflicted stab wounds with a glass piece under the influence of alcohol. This led
      to evisceration and later degloving injury to the small bowel. He recovered
      following surgery.

PMID- 11990337
TI  - Acute pancreatitis with hemobilia following percutaneous liver biopsy.
AB  - Hemobilia following liver biopsy is rare and acute pancreatitis associated with
      hemobilia in such a situation is rarer. We report a 55-year-old man with
      ulcerative colitis and hepatitis C-positive liver disease who developed acute
      pancreatitis following liver biopsy. Surgical removal of blood clots from the
      biliary tree led to recovery.

PMID- 11990338
TI  - Hereditary angioedema with recurrent abdominal pain.
AB  - Hereditary angioedema is a rare disorder characterized by quantitative or
      qualitative deficiency of complement C1 esterase inhibitor. We report a family
      whose members presented with recurrent angioedema and abdominal pain; the
      diagnosis was confirmed by quantitative assay of C1 inhibitor. The index patient
      was treated with danazol and was relieved.

PMID- 11990339
TI  - Ranitidine alone and in combination with domperidone in reflux-type dyspepsia.

PMID- 11990340
TI  - Study of three hepatobiliary agents in experimental animals.

PMID- 11990341
TI  - Multicenter phase III clinical trial of otilonium bromide in irritable bowel
      syndrome.

PMID- 11990342
TI  - Spontaneous perforation of common bile duct in pregnancy.

PMID- 11990343
TI  - Underestimation of cost of hepatitis B vaccine in India.

PMID- 11990344
TI  - Nonspecific jejunoileitis.

PMID- 11990345
TI  - Intestinal ascariasis: a new CT sign.

PMID- 11990347
TI  - Temporal profile of cortical perfusion and microcirculation after controlled
      cortical impact injury in rats.
AB  - Impaired cerebral perfusion contributes to evolving posttraumatic tissue damage.
      Spontaneous reversibility of reduced perfusion within the first days after injury
      could make a persisting impact on secondary tissue damage less likely and needs
      to be considered for possible therapeutic approaches. The present study was
      designed to characterize the temporal profile and impact of trauma severity on
      cortical perfusion and microcirculation during the first 48 h after controlled
      cortical impact injury (CCI). In 10 rats, pericontusional cortical perfusion and
      microcirculation using laser Doppler flowmetry (LDF) and orthogonal polarization
      spectral (OPS) imaging were assessed before, and at 4, 24, and 48 h after CCI.
      Influence of trauma severity was studied by varying the penetration depth of the
      impactor rod (0.5 vs. 1 mm), thereby inducing a less and a more severe contusion.
      Mean arterial blood pressure (MABP), arterial blood gases, and blood glucose were
      monitored. With unchanged MABP and paCO2, cortical perfusion and microcirculation
      were significantly impaired during the first 48 h following CCI. Hypoperfusion
      observed at 4 h related to vasoconstriction and microcirculatory stasis preceded
      a long-lasting phase of hyperperfusion at 24 and 48 h reflected by vasodilation
      and increased flow velocity in arterioles and venules. Hyperperfusion was mostly
      pronounced in rats with a less severe contusion. Following CCI, trauma severity
      markedly influences changes in pericontusional cortical perfusion and
      microcirculation. Overall, pericontusional cortical hypoperfusion observed within
      the early phase preceded a long lasting phase of hyperperfusion up to 48 h after
      CCI.

PMID- 11990346
TI  - Genes preferentially induced by depolarization after concussive brain injury:
      effects of age and injury severity.
AB  - Fluid percussion (FP) brain injury leads to immediate indiscriminate
      depolarization and massive potassium efflux from neurons. Using Northern
      blotting, we examined the post-FP expression of primary response/immediate early
      genes previously described as induced by depolarization in brain. RNA from
      ipsilateral and contralateral hippocampus was harvested from immature and adult
      rats 1 h following mild, moderate, or severe lateral fluid percussion injury and
      compared against age-matched sham animals. C-fos gene expression was used as a
      positive control and showed marked induction in both pups (6-25-fold with
      increasing severity) and adults (9.7-17.1-fold). Kinase-induced-by-depolarization
      1 (KID-1) and salt-inducible kinase (SIK) gene expression was increased in adult
      (KID-1 1.5-1.6-fold; SIK 1.3-3.9-fold) but not developing rats. NGFI-b RNA was
      elevated after injury in both ages (pups 1.8-6.1-fold; adults 3.5-5-fold), in a
      pattern similar to that seen for c-fos. Secretogranin I (sec I) demonstrated no
      significant changes. Synaptotagmin IV (syt IV) was induced only following severe
      injury in the immature rats (1.4-fold). Our results reveal specific severity- and
      age-dependent patterns of hippocampal immediate early gene expression for these
      depolarization-induced genes following traumatic brain injury. Differential
      expression of these genes may be an important determinant of the distinct
      molecular responses of the brain to varying severities of trauma experienced at
      different ages.

PMID- 11990348
TI  - Attenuation of working memory and spatial acquisition deficits after a delayed
      and chronic bromocriptine treatment regimen in rats subjected to traumatic brain
      injury by controlled cortical impact.
AB  - Cognitive impairments are pervasive and persistent sequelae of human traumatic
      brain injury (TBI). In vivo models of TBI, such as the controlled cortical impact
      (CCI) and fluid percussion (FP), are utilized extensively to produce deficits
      reminiscent of those seen clinically with the hope that empirical study will lead
      to viable therapeutic interventions. Both CCI and FP produce spatial learning
      acquisition deficits, but only the latter has been reported to impair working
      memory in rats tested in the Morris water maze (MWM). We hypothesized that a CCI
      injury would impair working memory similarly to that produced by FP, and that
      delayed and chronic treatment with the D2 receptor agonist bromocriptine would
      attenuate both working memory and spatial learning acquisition deficits. To test
      these hypotheses, isoflurane-anesthetized adult male rats received either a CCI
      (2.7 mm deformation, 4 m/sec) or sham injury, and 24 h later were administered
      bromocriptine (5 mg/kg, i.p.) or vehicle, with continued daily injections until
      all behavioral assessments were completed. Motor function was assessed on beam
      balance and beam walking tasks on postoperative days 1-5 and cognitive function
      was evaluated in the MWM on days 11-15 for working memory (experiment 1) and on
      days 14-18 for spatial learning acquisition (experiment 2). Histological
      examination (hippocampal CA1 and CA3 cell loss/survival and cortical lesion
      volume) was conducted 4 weeks after surgery. All injured groups exhibited initial
      impairments in motor function, working memory, and spatial learning acquisition.
      Bromocriptine did not affect motor function, but did ameliorate working memory
      and significantly attenuated spatial acquisition deficits relative to the injured
      vehicle-treated controls. Additionally, the injured bromocriptine-treated group
      exhibited significantly more morphologically intact CA3 neurons than the injured
      vehicle-treated group (55.60 +/- 3.10% vs. 38.34 +/- 7.78% [p = 0.03]). No
      significant differences were observed among TBI groups in CA1 cell survival
      (bromocriptine, 40.26 +/- 4.74% vs. vehicle, 29.13 +/- 6.63% [p = 0.14]) or
      cortical lesion volume (bromocriptine, 17.78 +/- 0.62 mm3 vs. vehicle, 19.01 +/-
      1.49 mm3 [p > 0.05]). These data reveal that CCI produces working memory deficits
      in rats that are similar to those observed following FP, and that the delayed and
      chronic bromocriptine treatment regimen conferred cognitive and neural protection
      after TBI.

PMID- 11990349
TI  - Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice.
AB  - Experimental investigations of single mild brain injury (SMI) show relatively
      little resultant cognitive impairment. However, repeated mild brain injuries
      (RMI), as those sustained by athletes (e.g., football, hockey, and soccer
      players) may have cumulative effects on cognitive performance and neuropathology.
      Numerous clinical studies show persistent, latent, and long-term consequences of
      RMI, unlike the episodic nature of SMI. The nature of repeated traumatic brain
      injury (TBI) introduces confounding factors in invasive and even semiinvasive
      animal models of brain injury (e.g., scar formation). Thus, the present study
      characterizes SMI and RMI in a noninvasive mouse weight drop model and the
      cumulative effects of RMI on cognitive performance. Investigation of drop masses
      and drop distances revealed masses of 50, 100, and 150 g dropped from 40 cm
      resulted in 0% mortality, no skull fracture, and no difference in acute
      neurological assessment following sham injury, SMI, or RMI. Cumulative effects of
      RMI were examined following four mild brain injuries 24 h apart induced by 50-,
      100-, or 150-g masses dropped from 40 cm through histological measures, mean
      arterial pressure, and measures of complex/spatial learning. RMI produced no
      overt cell death within the cortex or hippocampus, no evidence of blood-brain
      barrier compromise, and no significant change in mean arterial pressure.
      Following testing in the Morris water maze (MWM) on days 7-11 after initial
      injury, mice in the RMI 100-g and RMI 150-g groups had significantly longer MWM
      goal latencies compared to sham, SMI 150-g, and RMI 50-groups. Additionally, the
      evident cognitive deficit manifested in the absence of observed cell death. This
      is the first study to show complex/spatial learning deficits following RMI,
      similar to the visual/spatial perception and planning deficits observed in
      clinical studies.

PMID- 11990350
TI  - Fiberoptic intraparenchymal brain pressure monitoring with the Camino V420
      monitor: reflections on our experience in 163 severely head-injured patients.
AB  - To assess the safety and accuracy of the Camino intraparenchymal sensor, we
      prospectively evaluated hemorrhagic complications, zero-drift, infection, and
      system malfunction in 163 patients monitored after a severe head injury. Mean
      duration of intracranial pressure (ICP) monitoring was 5 +/- 2.2 days (range: 12
      h to 11 days). Of the 141 patients with a control CT scan, four showed a 1-2-cc
      collection of blood at the catheter's end. When removed, the sensors underread
      the true ICP value (negative zero-drift) in 80 of the 126 sensors evaluated
      (63.5%). Fourteen sensors showed no zero-drift, and 32 sensors overread the true
      ICP value (positive zero-drift) (median: -1 mm Hg; interquartile range: -4 to +1
      mm Hg). No significant relationship was found between zero-drift, the surgeon who
      implanted the sensor, intracranial hypertension, or duration of ICP monitoring.
      No clinical infections could be attributed to the devices. Sixteen patients
      (9.8%) required more than one ICP sensor due to malfunctioning of the system. In
      conclusion, continuous ICP monitoring using the Camino intraparenchymal sensor
      has a low complication rate. However, this sensor may underread the real ICP
      values in a high number of patients. The lack of correlation between duration of
      ICP monitoring and zero-drift suggests that, contrary to the recommendations of
      other reports, the intraparenchymatous Camino sensor can provide reliable
      readings after the fifth day of use.

PMID- 11990351
TI  - Subarachnoid hemorrhage induces dynamic changes in regional cerebral metabolism
      in rats.
AB  - Following a subarachnoid hemorrhage (SAH), adult rats exhibit dynamic regional
      changes in cerebral glucose metabolism characterized by an increase in metabolic
      rates and a subsequent upregulation of cytochrome oxidase (CO). We evaluated both
      local cerebral metabolic rates for glucose (ICMRglc: (mol/100 g/min) and CO in 23
      brain regions of interest (ROI). Sham animals underwent anesthesia and
      superficial surgery; saline-controls received an injection of 0.9% saline into
      the cisterna magna; and SAH rats received an injection of autologous blood into
      the cisterna magna. This blood, measured by albumin labeled with radioactive
      carbon 14, distributed throughout the brain but predominated ventrally. After
      experimental animals were sacrificed at day 0 (3 h), 1, 3, and 7 days
      postinjection, ROI were analyzed using [14C]2-deoxy-D-glucose autoradiography and
      CO histochemistry. ICMRglc in SAH rats increased in many regions (ranging from
      0.7% to 32.2% above sham levels). Cytochrome oxidase also increased from 1% to 9%
      above sham levels, peaking on day 3. Conversely, saline-controls exhibited
      prolonged depression of ICMRglc (ranging from 11% to 35% below sham levels) and
      CO (ranging from 4% to 11% below sham levels) from day 0 through day 7. All
      saline-control ROI for all time points showed this metabolic depression, and
      between 91% and 95% of saline-control ROI presented lower CO levels as compared
      to sham. Overall, ICMRglc and CO levels were greater in SAH than in saline
      control ROI. However, when considering the influence of subarachnoid blood on
      metabolic changes in SAH animals, both CO and 2DG levels did not correlate well
      with the amount of 14C-albumin binding. While previous studies have measured both
      metabolic rates of glucose and CO soon after SAH, this is the first to
      simultaneously conduct these measurements in the same SAH rat model.

PMID- 11990352
TI  - Release of excitatory amino acids in the penumbra of a focal cortical necrosis.
AB  - A cortical tissue necrosis from focal trauma expands between 30% and 300% from
      its initial size within 24 h, depending on the species studied. To shed light on
      the pathophysiological processes in the penumbra 1 zone after a focal cortical
      lesion, the release of excitatory amino acids into the traumatic penumbra zone 1
      was measured throughout the entire period of necrosis expansion. A microdialysis
      probe was inserted at an oblique angle into the cortex of Sprague-Dawley rats 2
      mm below the brain surface. One day later, a highly standardized cortical
      freezing lesion was induced at the brain cortex above the microdialysis probe.
      Dialysate was continuously collected prior to, during, and up to 24 h after
      trauma and analyzed for primary amino acids. In each animal, it was confirmed
      histologically that the tip of the microdialysis probe was localized in the gray
      matter in close proximity to the primary lesion. Following induction of the
      trauma, a statistically significant sharp increase of the dialysate level of
      aspartate, glutamate, glycine, and serine was observed. Thereafter, the dialysate
      levels of these amino acids returned to baseline levels without any further
      increase throughout the remaining observation period. This process ranged in time
      from a few minutes to a few hours. The level of alanine in the dialysate was
      essentially not altered throughout the experiment. Although the early post
      traumatic increase of the excitatory neurotransmitters aspartate and glutamate
      may well contribute to the secondary lesion growth of a cortical necrosis after
      trauma, glutamate receptor targeted therapeutic intervention may be in view of
      these findings of limited use when initiated post trauma.

PMID- 11990353
TI  - Heme oxygenase-1 expression after spinal cord injury: the induction in activated
      neutrophils.
AB  - Tissue damage and neurological dysfunction after spinal cord injury may result,
      in part, from delayed or secondary mechanisms that appear to involve several
      endogenous factors. Among them, neutrophils are known to play important roles in
      the pathomechanisms of the secondary injury, that is, neutrophils are activated
      by an interaction with the endothelial cells, migrate into the damaged tissue and
      release several kinds of proteases or oxygen radicals. In the present study, we
      examined heme oxygenase-1 expression in the damaged spinal cord. The
      administration of an inhibitor of heme oxygenase-1 in vivo produced a delayed
      recovery of motor function after spinal cord injury, suggesting that heme
      oxygenase-1 may play roles as an endogenous anti-inflammatory enzyme and
      protective gene in the damaged and inflammatory tissue. We found that many
      neutrophils expressing heme oxygenase-1 mRNA and protein were recruited into the
      damaged spinal cord with extensive hemorrhages during early stage of spinal cord
      injury. In an in vitro study, neutrophils incubated with proinflammatory
      cytokines, such as interleukin-1, 6 or interferon-gamma, expressed heme oxygenase
      1 mRNA and protein. Based on these findings we conclude that the activated
      neutrophils can express heme oxygenase-1 in the injured spinal cord tissue,
      perhaps expecting modulatory and neuroprotective actions in the inflammatory
      response to spinal cord injury.

PMID- 11990354
TI  - Increased protein oxidation and decreased creatine kinase BB expression and
      activity after spinal cord contusion injury.
AB  - Traumatic injury to the spinal cord triggers several secondary effects, including
      oxidative stress and compromised energy metabolism, which play a major role in
      biochemical and pathological changes in spinal cord tissue. Free radical
      generation and lipid peroxidation have been shown to be early events subsequent
      to spinal cord injury. In the present study, we demonstrated that protein
      oxidation increases in rat spinal cord tissue after experimental injury. As early
      as h after injury, the level of protein carbonyls at the injury epicenter was
      significantly higher than in control (169%, p < 0.05) and increased gradually
      over the next 4 weeks to 1260% of control level. Both caudal and rostral parts of
      the injured spinal cord demonstrated a mild increase of protein carbonyls by 4
      weeks postinjury (135-138%, p < 0.05). Immunocytochemical analysis of protein
      carbonyls in the spinal cord cross-sections showed increased protein carbonyl
      immunoreactivity in the epicenter section compared to rostral and caudal sections
      of the same animal or control laminectomy animals. Increased protein carbonyl
      formation in damaged spinal cord tissue was associated with changes in activity
      and expression of an oxidative sensitive enzyme, creatine kinase BB, which plays
      an important role in the maintenance of ATP level in the CNS tissue. Damage to CK
      function in the CNS may severely aggravate the impairment of energy metabolism.
      The results of our study indicate that events associated with oxidative damage
      are triggered immediately after spinal cord trauma but continue to occur over the
      subsequent 4 weeks. These results suggest that antioxidant therapeutic strategies
      may be beneficial to lessen the consequences of the injury and potentially
      improve the restoration of neurological function.

PMID- 11990355
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced down-regulation of glucose
      transporting activities in mouse 3T3-L1 preadipocyte.
AB  - The possibility that 3T3-L1 preadipocytes, while the level of its glucose uptake
      activity is relatively low, may offer a useful tool for studying the cause for
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced "lipolytic response" was
      studied. It was established first, that TCDD causes reduction of glucose uptake,
      one of the hallmark events of the lipolytic process. Then the function of c-Src
      was investigated. The antisense c-src oligonucleotide decreased the inhibitory
      action of TCDD on glucose uptake activity in a sequence specific manner. Since
      antisense oligonucleotides are known to own their blocking effects to their
      ability to reduce translation of proteins, Western blotting analysis was
      performed to verify their effectiveness. As expected, the treatment of pre
      adipocytes with antisense c-src oligonucleotide reduced c-Src in a sequence
      specific manner. The treatment of antisense c-src oligonucleotide alone was
      sufficient to diminish the inhibitory action of TCDD on glucose uptake activity
      in 3T3-L1 cells, indicating that c-Src is somehow involved in the action of TCDD.
      In a similar manner, the contribution of c-Fos was investigated using antisense c
      fos oligonucleotide, since c-Fos is known to be one of the most affected proteins
      by c-Src activation among AP-1 members. The treatment of antisense c-fos
      oligonucleotide did not block the effect of TCDD on glucose uptake activity in
      3T3-L1 cells. Therefore, it is unlikely that c-Fos is very important in the
      lipolytic signal transduction of TCDD mediated through c-Src. In order to
      determine the relationship between c-Src and c-Myc in the mitotic signal
      transduction pathway, the effect of antisense c-myc oligonucleotide was
      investigated. Basically the same result as antisense c-src oligonucleotide
      experiment was obtained thereby, suggesting the importance of c-Myc as well as c
      Src in the signal transduction of TCDD. To show the effect of antisense c-myc
      oligonucleotide treatment, the level of c-Myc protein by Western blotting and
      electrophoretic gel-mobility shift assay was assessed. However, antisense c-myc
      oligonucleotide treatment increased the activity of c-Myc in a sequence specific
      manner. This may be the result of cellular compensatory response to the initial
      suppression of c-Myc by antisense treatment. The observation that antisense c-fos
      oligonucleotide could not block the effect of TCDD indicates that this
      preadipocyte model is different from the adipocyte differentiation model.

PMID- 11990356
TI  - Modelling of atrazine transport in the presence of surfactants.
AB  - Laboratory experiments were conducted to examine the effect of detergents on
      transport of atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine]
      through loam and sandy loam soils under saturation conditions. The Convection
      Dispersion Equation (CDE) was used to model and quantify the effects of
      detergents on atrazine model parameters: the retardation factor (R), pore
      velocity (v) and dispersion coefficient (D). The transport parameters were
      estimated using moment technique and partition coefficient obtained from batch
      experiments and compared with best-fitted parameters, R and D, keeping pore
      velocity constant. Results indicated the CDE model was not successful in
      predicting atrazine transport in the presence of surfactants at high
      concentrations. In the case of anionic surfactant with Elora loam, the average
      predicted R and D from moment technique of 3.4 and 11.1 cm2/h, respectively were
      significantly different than fitted parameters (R = 39 and D = 227 cm2/h). The
      poor performance of CDE in the presence of surfactants results from
      physiochemical changes in herbicide solubility and retention to the soil matrix
      rather than changes in soil hydraulic properties since the predicted pore water
      velocities from moment technique were similar to those measured during leaching
      experiments. Nevertheless, BTC analysis with CDE showed that land application of
      anionic surfactant (sulphonic) significantly increased R and D and decrease v for
      both soils. Addition of sulphonic increased R of atrazine by 12 and 26 folds for
      loam and sandy loam soils, respectively. On the other hand non-ionic surfactants
      seemed to decrease R, especially in sandy loam soil, thus facilitating atrazine
      leaching through soil. Non-equilibrium conditions seemed to govern atrazine
      transport in the presence of surfactants; double peaks in breakthrough curves
      were observed, indicating a need for mathematical models to account for such
      phenomena. Atrazine dispersion and tailing seemed to be higher through Elora loam
      compared to Caledon sandy loam due to higher aggregation of the Elora soil.

PMID- 11990357
TI  - Persistence and degradation of coumaphos in model cattle dipping vats.
AB  - The stability of coumaphos [O,O-diethyl O-(3-chloro-4-methyl-2-oxo-2H-1
      benzopyran-7 yl)phosphorothioatel was studied in model dipping vats under field
      conditions using 14C-labelled and unlabelled coumaphos, with or without
      additives. The stability of coumaphos in model vats increased significantly by
      maintaining a pH of 5 by addition of superphosphate. Copper sulphate amendment
      did not seem to have any additional effect on stability. Potasan was the major
      metabolite in addition to chlorferon and 4-methylumbelliferone. Coumaphos
      concentration was doubled in the sediment of vat treated with copper sulphate as
      compared to the control vat as a result of emulsion breakdown. Chlorferon was the
      only metabolite detected in the sediment of the former vat indicating inhibition
      of the anaerobic degradation.

PMID- 11990358
TI  - Lesions induced by 2,4-D and chlorpyrifos in tench (Tinca tinca L.): implication
      in toxicity studies.
AB  - This study was undertaken to demonstrate the toxicity of two pesticides,
      chlorpyrifos (O,O-diethyl 0-3,5,6-trichloro-2-pyridyl phosphorothioate) and 2,4-D
      (Dichlorophenoxyacetic acid) to tench (Tinca tinca Linnaeus). Pathological
      samples of damaged tench kidney showing lesions were taken for statistical
      analysis in order to quantify different parameters. Analysis revealed differences
      in the action and/or action time of the two pesticides. These differences were
      more acute in the case of 2,4-D thereby indicating a greater toxicity. These
      differences, expressed by mathematical formulae of numerical variables, would
      enable, a priori, the identification of the responsible pesticide and the time of
      acting in new natural cases of poisonings with these substances.

PMID- 11990359
TI  - Toxicity and biodegradation of diamines.
AB  - Phytotoxicity and cytotoxicity of 2,4-diaminotoluene (2,4-D), 4,4'
      methylenedianiline (4,4-D), and 1,6-hexanediamine (1,6-D) were investigated by
      observing the germination of young radish seeds and the viability of HeLa cells,
      respectively. 2,4-D showed the highest, 4,4-D intermediate, and 1,6-D lowest
      cytotoxicity. However, the phytotoxicity decreased in the order of 4,4-D > 2,4-D
      > 1,6-D. Contrary to the results previously reported, in the modified Sturm test
      the activated sludge degraded 2,4-D and 4,4-D as well as 1,6-D without any pre
      acclimation. Ochrobacterium antropi was isolated for degradation of 2,4-D and 4,4
      D and Pseudomonas citronellolis for 1,6-D degradation. Thielevia sp. was isolated
      as 2,4-D degrading fungus and Aspergillus sp. as 4,4-D and 1,6-D degrading
      fungus. The fungi degraded the diamines faster than the bacteria.

PMID- 11990360
TI  - Photocatalytic oxidation of pesticide rinsate.
AB  - Pesticide rinsate has been considered as one of the major threats for the
      environment. In this study, photocatalysts such as TiO2 and O3 were used to
      promote the efficiency of direct UV photolysis to prevent such wastewater
      pollution. Carbofuran (a carbamate pesticide) and mevinphos (an organophosphate
      pesticide) with a concentration of 100 mg/L were selected as the test pesticide
      rinsates. Parent pesticide compound, COD, and microtoxicity analysis were
      employed to investigate the effect of photocatalyst on the degradation efficiency
      of pesticide in rinsate. It was found that the photocatalytic oxidation process
      (UV/O3, UV/TiO2) showed much higher COD removal and microtoxicity reduction
      efficiency for pesticide rinsate than did direct UV photolysis under the imposed
      conditions, suggesting that photocatalytic oxidation processes such as UV/O3 and
      UV/TiO2 could be a better alternative to treat pesticide rinsate. In addition, it
      was noted that increasing the initial pH of mevinphos rinsate to a basic level
      was required to reach higher COD removal efficiency and positive microtoxicity
      reduction efficiency while it was not necessary for the treatment of carbofuran
      rinsate.

PMID- 11990361
TI  - Effect of surfactants on persistence of azadirachtin-A (neem based pesticide).
AB  - Photostability of azadirachtin-A, a neem based pesticide, was studied in the
      presence of non-ionic surfactants. Surfactants such as Span-80, Atlox 3400B,
      Tween-80, Agrimul 52B, and Agrimul N4S enhanced the rate of photodegradation of
      azadirachtin-A, whereas surfactants such as Triton-X, Emulsol CFA, Tween-20,
      Emulsol MAS, and Emulsol-N-33 decreased the rate of degradation. Emulsol-N-33 was
      found to be the most effective surfactant, as half life of azadirachin-A in the
      presence of Emulsol-N-33 was found to be 94.93 min in comparison to 48 min for
      azadirachtin-A alone under UV light.

PMID- 11990362
TI  - Movement of leachate from beneath turkey litter sited over chalk in southern
      England.
AB  - Farm waste stores are widespread in the UK, with many overlying the principal
      aquifer, the Chalk. The stores pose a threat to groundwater quality through the
      infiltration of high concentrations of nitrogen species and organic carbon
      together with pathogenic microbes. Two cored boreholes have been drilled into the
      unsaturated chalk to depths of 15 and 20 metres, respectively, through a site
      which has been used to store turkey litter for in excess of 20 years. Porewaters
      were extracted from the cores and analysed for a range of chemical elements. In
      addition, chalk core material was also taken for microbial examination. Both
      boreholes showed very high concentrations of nitrate-N (3000 mg/L), ammonia (5000
      mg/L), organic carbon (3000 mg/L), and potassium (10,000 mg/L) in the top 5
      metres of the profile. Below this depth concentrations declined dramatically.
      Highest concentrations were found in the borehole constructed in the middle of
      the site. The borehole constructed at the edge of the store showed much lower
      concentrations but did show a peak of nitrate around 10 metres below ground
      level. The apparent lack of movement beneath the centre of the store suggests the
      turkey litter is relatively impermeable and most leaching occurs where the
      covering of litter is thin or when the litter is annually cleared. If the
      leachate continues to migrate at this apparent rate, it will take more than 100
      years to reach the water table.

PMID- 11990363
TI  - Nutritional assessment of transgenic sweetpotato on body weight, lipid, and
      protein status in hamsters.
AB  - The objectives of the present study were to evaluate the nutritional quality of
      genetically modified sweetpotato (genotype PI318846-3) on growth, lipid
      metabolism, and protein metabolism of hamsters. Three different diets made with
      transgenic and nontransgenic sweetpotato protein flour including a control diet
      with casein were fed to male Golden Syrian hamsters for 28 days. The protein
      efficiency ratio (1.35 +/- 0.01) of the transgenic sweetpotato protein diet was
      significantly higher (p<0.05) than the nontransgenic sweetpotato and control
      diets. Plasma albumin and plasma total protein concentrations of hamsters fed the
      sweetpotato diets were significantly lower (p<0.05) than that of the control. The
      casein diet (control) produced hypercholesterolemia in hamsters, whereas
      sweetpotato diets maintained lower plasma and liver total and LDL-cholesterol
      concentrations in hamsters. Sweetpotatoes contain less amount of protein to
      maintain the normal animal growth; however, transgenic sweetpotato has good
      quality protein that supported the growth of hamsters better than nontransgenic
      sweetpotato.

PMID- 11990364
TI  - Atrazine effects on in vitro maturation and in vitro fertilization in the bovine
      oocyte.
AB  - The effect of low levels of atrazine (2-chloro-4-ethylamino-6-isopropylamino-s
      triazine) on in vitro oocyte maturation, in vitro capacitation of sperm, or in
      vitro fertilization of bovine oocytes and on the quality of blastocyst formation
      was studied. Bovine oocytes collected from abattoir ovaries were matured,
      fertilized, and developed to the blastocyst stage in vitro. Embryos that reached
      a morula or blastocyst stage were stained with Hoechst 33258 stain to determine
      the number of blastomeres per embryo. Three bulls whose fertilization rates were
      proven consistent among straws were used for this study. Atrazine was tested at
      concentrations of 0.01, 0.1, 1, and 10 microM in either the maturation medium,
      sperm capacitation medium, or the fertilization medium. Because atrazine was
      dissolved in ethanol, an ethanol control was used to determine any possible
      effects of ethanol on the in vitro process. The addition of atrazine to both the
      maturation and fertilization media did not result in any significant difference
      in fertilization rates between the controls and the treatments. In the
      capacitation medium, a significant difference between the controls and the
      atrazine levels of 0.1, 1, and 10 microM was noted for one bull. Atrazine did not
      affect the number of blastomeres per embryo. There was not a significant
      difference (p>0.05) in the number of blastomeres per embryo between the controls
      and the different levels of atrazine in each medium. This study indicates that
      low levels of atrazine do not have an effect on in vitro fertilization rates or
      the number of blastomeres per embryo produced in vitro.

PMID- 11990365
TI  - Evaluation of potential dermal exposure of pesticide spray operators in
      greenhouses by use of visible tracers.
AB  - In the present study, the potential dermal and inhalation exposure of the
      operator was measured, following simulation of insecticide application with the
      dye tracer Sunset Yellow in greenhouse cucumbers and tomatoes. For the monitoring
      of operator exposure, the whole body technique was used. The potential inhalation
      exposure was measured with a personal air sampler equipped with a glass fiber
      filter. The potential dermal operator exposure ranged from 84.4 to 526.7 ml of
      spray solution (s.s.)/h for the whole body and from 18.5 to 62.5 ml s.s./h for
      hands in the case of greenhouse cucumbers. The respective inhalation exposure was
      between 0.17 and 1.0 ml s.s./h. For greenhouse tomatoes, the potential body
      exposure was in the range of 22.4 to 62.1 ml s.s./h. The hand exposure varied
      from 5.5 to 6.1 ml s.s./h. The potential inhalation exposure was in the range of
      0.33 to 0.43 ml s.s./h. The potential dermal operator exposure is a highly
      variable parameter, with a variation factor higher than 100% in many cases. One
      of the most critical factors for the determination of both potential dermal and
      inhalation exposure is the application pressure. Other field and operational
      conditions, including unpredictable factors, are also important for the
      determination of operator exposure levels. The measured potential dermal operator
      exposure values were above the levels of exposure estimated with mathematical
      models.

PMID- 11990366
TI  - Distribution of aldrin and its epoxide (dieldrin) in egg-forming tissues and eggs
      of laying hens following an oral application.
AB  - Laying hens were treated orally with a single dose of aldrin (1,2,3,4,10,10
      hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5,8-dimethanonaphthalene, AD) 1 mg kg(-1)
      bw. Concentrations (microg g(-1)) of AD or its epoxide, dieldrin (1,2,3,4,10,10
      hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydroendo-,exo-1,4:5,8-dimetha
      nonaphthalene, DD), in the main tissues involved in egg formation (blood, liver,
      ovary, and oviducts) and egg yolk, collected at 1 day after AD dosing, were
      determined by normal-phase high-performance liquid chromatography. The limits of
      determination were 0.07 microg g(-1) for AD and 0.08 microg g(-1) for DD,
      respectively. In extractable fats from the above tissues and egg yolk, AD was
      found in the egg yolk; however, no AD was found in tissues involved in egg
      formation. DD was found in all tissues examined here. The DD level was highest in
      the liver and was lowest in the blood (P<0.01). These results suggest that the
      epoxidation of AD to DD occurred rapidly in the hen.

PMID- 11990367
TI  - Light-induced transformation of tribenuron-methyl on glass, soil, and plant
      surface.
AB  - Photolysis of tribenuron-methyl (methyl 2-[[[[N-(4-methoxy-6-methyl-1,3,5triazin
      2-yl)methylamino]carbonyl]amino]sulfonyl]benzoate), a sulfonylurea herbicide, was
      studied as thin film on glass surface, soil surface, and plant surface. A number
      of photoproducts such as 4-methoxy-6-methyl-2-aminomethyl-1,3,5-triazine; methyl
      2-(aminosulfonyl) benzoate; N-(2-carbomethoxyphenyl)-N-(4-methoxy-6-methyl-1,3,5
      triazin-2-yl)-N'-methylurea; N-(2-carbomethoxyphenyl sulfonyl)-N-methyl urea; o
      benzoic sulfimide and 4-methoxy-6-methyl-2-amino-1,3,5-triazine were identified
      by comparison of their GC-MS with the authentic standards. The rate of
      degradation in all the cases followed first-order kinetics with a statistically
      significant correlation coefficient. Rate of photodegradation was greater on
      glass surface than on soil surface.

PMID- 11990368
TI  - Determination of PAHs in wastewater irrigated agricultural soil using accelerated
      solvent extraction.
AB  - A procedure was developed for determination of 16 polycyclic aromatic
      hydrocarbons (PAHs) in heavily contaminated paddy soil from wastewater irrigated
      farmland near Tianjin. The sample was distilled with accelerated solvent
      extraction (ASE), purified by a silica gel column, and measured with GC/MS. The
      optimal conditions for the distillation were at 140 degrees C (1500 psi) with a
      1:1 mixture of dichloromethane and acetone for 5 min. Application of cyclohexane
      for extract transfer improved the recovery when the ASE extraction was followed
      by a silica gel cleanup procedure. Recoveries from the method for 16 PAHs ranged
      from 57-140% with the coefficients of variation of the results ranging from 0.35%
      to 5.75%. The total 16 PAHs in a composite sample collected from a wastewater
      irrigated paddy field near Tianjin was 3.90 mg/kg.

PMID- 11990369
TI  - Metal accumulation from contaminated food and its effect on growth of juvenile
      landsnails Helix engaddensis.
AB  - Metal accumulation by juvenile landsnails, Helix engaddensis, and its effect on
      growth rate was studied over a 5-week period of exposure and 2 weeks of recovery.
      An artificial food contaminated with Cu (4-2500 microg x g(-1)), Cd (50-800
      microg x g(-1)), Pb, and Zn (20-12500 microg x g(-1)) was used. During the 7
      weeks of the experiment, mortality rates were 20, 27, 30, and 38% among snails
      fed Cu-, Pb-, Zn-, and Cd-contaminated food, respectively. According to the
      ability to inhibit growth, metals were found to have the following order: Cd > Zn
      > Cu = Pb. Inhibitory effects of dietary metals started to be significant from
      the third week of exposure on. Inhibition of growth by Pb and Cu was found to be
      reversible, and within the first week of recovery, snails erupted their
      aestivation and resumed feeding and growth to gain weights similar to those of
      the control groups. Snails fed Cd- or Zn-contaminated food failed to resume
      growth during the 2 weeks of recovery. This indicates that in the case of Cu and
      Pb, growth inhibition was mainly due to starvation due to food rejection and
      aestivation. On the other hand, growth inhibition caused by Cd and Zn may have
      been resulting from irreversible toxicity. Therefore, snails were assumed to be
      sensitive to Cd and Zn but tolerant to Cu and Pb. Accumulation of Cu and Pb was
      significant only at the highest concentrations. At low and medium concentrations,
      no signs of accumulation were observed, indicating regulation at these
      concentrations. Cd and Zn accumulation starts at low concentrations but became
      significant at medium and high levels indicating accumulation of these metals.

PMID- 11990370
TI  - (Z)-7-dodecenyl acetate: a supernormal stimulus of Trichoplusia ni (Hubner)
      [Lepidoptera: Noctuidae] sex pheromone behavior.
AB  - Males discriminate between the single most important individual component of the
      sex pheromone of the female cabbage looper, Trichoplusia ni (Hubner), (Z)-7
      dodecenyl acetate (Z7-12:Ac), and a mixture containing Z7-12:Ac and the other
      five putative components. The manifestation of discrimination is not an
      enhancement of captures by the mixture, rather, it is a reduction of captures in
      a paired trap baited with Z7-12:Ac by itself. Previous experiments showed that
      either or both of (Z)-7-tetradecenyl acetate (Z7-14:Ac) and (Z)-9-tetradecenyl
      acetate (Z9-14:Ac) were responsible for this discrimination. This report provides
      evidence that Z7-14:Ac is more active than Z9-14:Ac, which appears to have no
      demonstrable effect on behavior. The results are discussed with reference to the
      behavior that is effected by the above three components, the composition of the
      native sex pheromone, and whether or not Z7-12:Ac might be a supernormal releaser
      of behavior.

PMID- 11990371
TI  - Composting duck excreta enriched wood shavings: C and N transformations and
      bacterial pathogen reductions.
AB  - Composting of agricultural and domestic wastes is used increasingly to reduce
      weight, volume, and odor; destroy animal and plant pathogens; and improve the
      quality of end-products to be used as soil amendments and growth substrates. The
      objective of this study was to investigate the transformation of C and N and the
      survival of bacterial populations and pathogenic bacteria during in-vessel
      composting of duck excreta enriched wood shavings. Two feedstocks, collected on
      different dates, were composted (C1 and C2) in an enclosed hall system equipped
      with an electromechanical turner. Temperature was continuously recorded, whereas
      moisture content and bacterial counts were determined twice a week. Data showed
      that, although the N content of C2 was only half of that of C1, both materials
      were fully biostabilized at the end of the composting period as indicated by
      extractable lipid ratios. In the compost with the low C/N ratio (C1), all
      bacterial populations were eliminated, whereas fecal streptococci, total
      coliforms, and gram-negative bacteria were still present in C2 at the end of the
      composting period. Our results emphasize that the composting of manures and other
      organic wastes needs to be properly managed to stabilize C and N and to eliminate
      or reduce bacterial populations.

PMID- 11990372
TI  - Feeling below PAR: proteinase-activated receptors and the perception of
      neuroinflammatory pain.

PMID- 11990373
TI  - Both populations and individuals are evolutionary targets: pharmacogenomic and
      cultural indicators.

PMID- 11990374
TI  - Pharmacogenomics--is there a role in antibiotic therapy?

PMID- 11990375
TI  - The HUGO Mutation Database Initiative. Human Genome Organization.

PMID- 11990376
TI  - Pharmacogenomic-guided drug development: regulatory perspective.

PMID- 11990377
TI  - Searching for type 2 diabetes genes: prospects in pharmacotherapy.

PMID- 11990378
TI  - A unique mouse model for succinic semialdehyde dehydrogenase deficiency with
      implications for gamma hydroxybutyrate intoxication.

PMID- 11990379
TI  - Pharmacogenetics of the arylamine N-acetyltransferases.
AB  - The arylamine N-acetyltransferases (NATs) are involved in the metabolism of a
      variety of different compounds that we are exposed to on a daily basis. Many
      drugs and chemicals found in the environment, such as those in cigarette smoke,
      car exhaust fumes and in foodstuffs, can be either detoxified by NATs and
      eliminated from the body or bioactivated to metabolites that have the potential
      to cause toxicity and/or cancer. NATs have been implicated in some adverse drug
      reactions and as risk factors for several different types of cancers. As a
      result, the levels of NATs in the body have important consequences with regard to
      an individual's susceptibility to certain drug-induced toxicities and cancers.
      This review focuses on recent advances in the molecular genetics of the human
      NATs.

PMID- 11990380
TI  - Adiponectin enhances insulin action by decreasing ectopic fat deposition.

PMID- 11990381
TI  - UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity.
AB  - The metabolism of irinotecan (CPT-11) involves sequential activation to SN-38 and
      detoxification to the pharmacologically inactive SN-38 glucuronide (SN-38G). We
      have previously demonstrated the role of UGT1A1 enzyme in the glucuronidation of
      SN-38 and a significant correlation between in vitro glucuronidation of SN-38 and
      UGT1A1 gene promoter polymorphism. This polymorphism (UGT1A1*28) is characterized
      by the presence of an additional TA repeat in the TATA sequence of the UGT1A1
      promoter, ((TA)7TAA, instead of (TA)6TAA). Here we report the results from a
      prospective clinical pharmacogenetic study to determine the significance of
      UGT1A1*28 polymorphism on irinotecan disposition and toxicity in patients with
      cancer. Twenty patients with solid tumors were treated with a 90 min i.v.
      infusion of irinotecan (300 mg m(-2)) once every 3 weeks. The frequency of UGT1A1
      genotypes was as follows: 6/6--45%, 6/7--35% and 7/7--20%, with allele
      frequencies of 0.375 and 0.625 for (TA)7TAA and (TA)6TAA, respectively. Patients
      with the (TA)7TAA polymorphism had significantly lower SN-38 glucuronidation
      rates than those with the normal allele (6/6>6/7>7/7, P = 0.001). More severe
      grades of diarrhea and neutropenia were observed only in patients heterozygous
      (grade 4 diarrhea, n = 1) or homozygous (grade 3 diarrhea/grade 4 neutropenia, n
      = 1 and grade 3 neutropenia, n = 1) for the (TA)7TAA sequence. The results
      suggest that screening for UGT1A1*28 polymorphism may identify patients with
      lower SN-38 glucuronidation rates and greater susceptibility to irinotecan
      induced gastrointestinal and bone marrow toxicity.

PMID- 11990382
TI  - Human sulfotransferase SULT2A1 pharmacogenetics: genotype-to-phenotype studies.
AB  - SULT2A1 catalyzes the sulfate conjugation of dehydroepiandrosterone (DHEA) as
      well as other steroids. As a step toward pharmacogenetic studies, we have
      'resequenced' SULT2A1 using 60 DNA samples from African-American and 60 samples
      from Caucasian-American subjects. All exons, splice junctions and approximately
      370 bp located 5' of the site of transcription initiation were sequenced. We
      observed 15 single nucleotide polymorphisms (SNPs), including three non
      synonymous coding SNPs (cSNPs) that were present only in DNA from African
      American subjects. Linkage analysis revealed that two of the nonsynonymous cSNPs
      were tightly linked. Expression constructs were created for all nonsynonymous
      cSNPs observed, including a 'double variant' construct that included the two
      linked cSNPs, and those constructs were expressed in COS-1 cells. SULT2A1
      activity was significantly decreased for three of the four variant allozymes.
      Western blot analysis demonstrated that decreased levels of immunoreactive
      protein appeared to be the major mechanism responsible for decreases in activity,
      although apparent Km values also varied among the recombinant allozymes. In
      addition, the most common of the nonsynonymous cSNPs disrupted the portion of
      SULT2A1 involved with dimerization, and this variant allozyme behaved as a
      monomer rather than a dimer during gel filtration chromatography. These
      observations indicate that common genetic polymorphisms for SULT2A1 can result in
      reductions in levels of both activity and enzyme protein. They also raise the
      possibility of ethnic-specific pharmacogenetic variation in SULT2A1-catalyzed
      sulfation of both endogenous and exogenous substrates for this phase II drug
      metabolizing enzyme.

PMID- 11990383
TI  - Tetanus antigen modulates the gene expression profile of aluminum phosphate
      adjuvant in spleen lymphocytes in vivo.
AB  - Adjuvants play an important role in stimulation of the immune response to
      antigens. Very little is known about the molecular mechanisms of this
      stimulation. Here we address this issue by studying gene expression profiles from
      spleen lymphocytes after in vivo immunization of mice with a clinically relevant
      vaccine, tetanus toxoid formulated with aluminum phosphate as adjuvant (TT(ADJ)),
      or the adjuvant alone (ADJ). The Th1/Th2 response to TT(ADJ) was obtained from a
      combination of up- and downstream markers to conventional cytokines, which were
      in good agreement with cytokine protein levels. A clustering algorithm revealed
      that ADJ elicited expression of 47 genes active in cytotoxic lymphocytes,
      inflammation, oncogenesis, stress, toxicity and cell cycle regulation. In TT(ADJ)
      these adjuvant-elicited genes were expressed at lower levels and a compensatory
      onset of protective and inhibitory genes was observed. We conclude that the
      antigen, to a larger extent than previously recognized, modulates the molecular
      mechanism of the aluminum phosphate adjuvant and that the identified genes may
      serve as predictive biomarkers in the development of new adjuvants and vaccines.

PMID- 11990384
TI  - Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is
      associated with response to modafinil.
AB  - The gene for catechol-O-methyltransferase (COMT) plays a key modulatory role in
      dopaminergic and noradrenergic neurotransmission. Recent evidence suggests that
      modafinil, like other stimulants, might act through the dopaminergic system. We
      have reported a sexual dimorphism and a strong effect of the COMT genotype on
      narcolepsy symptoms and hypothesized that response to modafinil treatment may be
      associated with the COMT genotype. Here we confirm that COMT genotype
      distribution between men and women narcoleptics is associated with response to
      modafinil. In addition, the optimal daily dose of modafinil is approximately 100
      mg lower in women narcoleptics and lower in all narcoleptics with low activity
      COMT genotype. Our results suggest that a sexual dimorphism in COMT activity
      affects the response to modafinil and probably to other dopaminergic stimulants.

PMID- 11990385
TI  - Metastatic medulloblastoma--therapeutic success through molecular target
      identification?

PMID- 11990386
TI  - The rise and fall in primary liver cancer mortality in Italy.

PMID- 11990387
TI  - Endoscopy, serology and histology in the diagnosis of coeliac disease.

PMID- 11990388
TI  - Clinical relevance of hepatocyte proliferative activity.

PMID- 11990389
TI  - Endoscopic markers in adult coeliac disease.
AB  - BACKGROUND: Various endoscopic markers have been described in coeliac disease,
      particularly in the second part of the duodenum, with minor attention generally
      being paid to the duodenal bulb. AIMS: To evaluate, prospectively, the presence
      of all endoscopic markers in the bulb and the second part of the duodenum on a
      large series of patients submitted to endoscopy for duodenal biopsy. PATIENTS AND
      METHODS. A total of 367 consecutive patients, submitted to endoscopy with
      duodenal biopsy for various indications, were considered. Biopsies were graded as
      normal, with partial villous atrophy (mild, moderate, severe) or with subtotal
      villous atrophy. Endoscopic markers and corresponding locations evaluated were:
      micronodular pattern [bulb and descending duodenum], mosaic appearance (bulb and
      descending duodenum), scalloped folds (descending duodenum), reduced or absent
      folds (descending duodenum). RESULTS: In 78 patients, a diagnosis of untreated
      coeliac disease was made. Endoscopic markers were seen in 73/78 patients, with
      only a single sign present (bulb or descending duodenum) in 12 patients. In the
      remaining 289 patients, normal histology and normal endoscopic findings were
      observed, except in two patients with reduced folds. Sensitivity, specificity,
      positive and negative predictive values and diagnostic accuracy regarding all
      endoscopic markers were 93.6%, 99.3%, 97.3%, 98.3% and 98.1%, respectively
      CONCLUSIONS: This study confirms the usefulness of endoscopic markers in
      detecting coeliac disease, underlining the importance of evaluating also
      abnormalities in the bulb and endoscopic single signs; although endoscopy may not
      detect all cases of coeliac disease, the recognition of endoscopic markers allows
      the selection for biopsy of unsuspected patients submitted to endoscopy for non
      specific symptoms.

PMID- 11990390
TI  - Analysis of medical compliance in gastro-oesophageal reflux disease patients
      referred to pre-surgical examination.
AB  - BACKGROUND: Despite potential of modern pharmacotherapy to control gastro
      oesophageal reflux disease and also to improve patients' quality of life, an
      efficient long-term management always depends on patients compliance with
      medication. AIMS: To evaluate and analyse potential aspects of compliance or non
      compliance with medical and clinical prescriptions in a selected group of gastro
      oesophageal reflux disease patients referred to pre-surgical examination because
      of persistent or recurrent symptoms. PATIENTS: A total of 182 gastro-oesophageal
      reflux disease patients have been divided by patient rating to 3 different
      subgroups: group 1/TC consisted of patients who subjectively stated to be totally
      compliant (n=71; 39%); group 2/PC of patients with partial compliance (n=65;
      36%), and group 3/NC consisted of patients with non-compliance (n=46; 25%) in
      relation to the prescriptions of their doctor taking care of their treatment.
      METHODS: All patients have been asked for potential aspects of compliance or non
      compliance. The following aspects have been analysed: understandable medical
      prescription, information about gastro-oesophageal reflux disease, subjective
      severity of gastro-oesophageal reflux disease-related symptoms, severity of
      disease, side-effects of medication, general rejection of medication, multi
      medication, patient age and sex, quality of life, and a specific construct of
      personality (health locus of control). RESULTS: Significant differences could be
      calculated between patients' age and gender showing that female and elderly
      patients are more compliant with medication. Group 1/TC patients suffered from a
      significantly longer period of symptoms and received medication for a longer
      period when compared to the other groups. Quality of life was impaired in all
      patients but patients in group 3/NC had a significantly better quality of life
      than patients in group 1/TC. The leading aspects for total compliance were: an
      understandable medical prescription (95%), high severity of perceived symptoms
      (76%) and of disease (88%). The major factors in group 2/PC patients have been
      unclear information about gastro-oesophageal reflux disease (41%), mild severity
      of perceived symptoms (59%), low severity of disease (30%), and a general
      rejection of medical treatment (21%). General rejection of drug treatment has
      been the major factor in group 3/NC patients (80%) which can be viewed in
      relation to patients' personality CONCLUSION: Compliance or non-compliance in
      this selected group of patients depended on several factors such as information,
      subjective severity of symptoms, severity of disease but, in addition, on
      patients' personality Therefore, new strategies for compliance with long-term
      treatment in gastro-oesophageal reflux disease patients should be discussed.

PMID- 11990391
TI  - Early treatment with lexipafant, a platelet-activating factor-receptor
      antagonist, is not sufficient to prevent pulmonary endothelial damage after
      intestinal ischaemia and reperfusion in rats.
AB  - BACKGROUND: Intestinal ischaemia-reperfusion can lead to pulmonary injury
      characterised by increased macromolecular leakage and leukocyte sequestration.
      Important mediators of ischaemia-reperfusion-associated injury include
      polymorphonuclear granulocytes and platelet-activating factor. AIM: To
      investigate the potential therapeutic inhibition of platelet-activating factor in
      intestinal ischaemia-reperfusion associated pulmonary injury, by use of a potent
      platelet-activating factor-receptor antagonist, lexipafant. METHODS: Rats were
      subjected to 30 minutes of intestinal ischaemia followed by 3 or 12 hours
      reperfusion. Lexipafant or saline was given intraperitoneally after 30 minutes
      reperfusion. RESULTS: Increased leakage of radiolabelled human serum albumin was
      found in the lungs after intestinal ischaemia followed by 3 or 12 hours
      reperfusion. Administration of lexipafant did not significantly prevent the
      increased leakage. Pulmonary myeloperoxidase content increased after intestinal
      ischaemia-reperfusion, indicating polymorphonuclear granulocyte sequestration
      through the pulmonary endothelium. The increase in interleukin-1beta seen after 3
      hours reperfusion was partly reversed by lexipafant. CONCLUSIONS: Pulmonary
      injury occurred following intestinal ischaemia-reperfusion, characterised by
      increased leakage of radiolabelled albumin over the endothelial barrier;
      correlating with increased pulmonary myeloperoxidase-content, implying
      involvement of polymorphonuclear granulocytes in the pathogenesis of remote organ
      injury after intestinal ischaemia-reperfusion. Lexipafant did not significantly
      decrease severity of pulmonary damage.

PMID- 11990392
TI  - Proliferating cell nuclear antigen assessed by a computer-assisted image analysis
      system in patients with chronic viral hepatitis and cirrhosis.
AB  - BACKGROUND: Assessment of liver cell proliferation by immunodetection of
      proliferating cell nuclear antigen may predict regenerative potential and
      survival of liver and hepatocellular carcinoma risk in patients with chronic
      viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and
      its clinical significance in a large cohort of patients with chronic viral
      hepatitis and different degree of liver damage by a computer assisted imaging
      analysis system. MATERIALS: Liver biopsies from 358 patients with chronic
      hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with
      hepatitis B virus, 10% with multiple infections) were studied. METHODS:
      Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave
      oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal
      antibody. Proliferating cell nuclear antigen labelling index was calculated by an
      automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean
      proliferating cell nuclear antigen labelling index ranged from 0.1% for patients
      with minimal changes to 3.6% for those with cirrhosis and hepatocellular
      carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher
      in males, in older patients, in multiple infections and in hepatitis C virus
      compared to hepatitis B virus related cases. By linear regression analysis,
      proliferating cell nuclear antigen labelling index correlated with older age,
      male gender; higher transaminase levels, hepatitis C virus, higher histological
      gradIng and staging: by multivariate analysis male gender, hepatitis C virus,
      higher grading and staging resulted as independent variables. Both hepatitis C
      virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate
      but those with hepatitis B virus had higher prevalence of liver cell dysplasia
      with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell
      nuclear antigen labelling index was a reliable assay for assessing liver cell
      proliferation rate in patients with chronic viral hepatitis and correlated with
      liver disease severity

PMID- 11990393
TI  - Fasting insulin and uric acid levels but not indices of iron metabolism are
      independent predictors of non-alcoholic fatty liver disease. A case-control
      study.
AB  - BACKGROUND: Non-alcoholic fatty liver disease is a common reason for
      hepatological consultation and may herald severe hepatic and extra-hepatic
      disease. The aetiopathogenesis of this condition is an area of increasing
      interest. AIM: To evaluate anthropometric and biochemical factors associated to
      non-alcoholic fatty liver disease in a case-control study. Methods. Demographic
      and biochemical data of 60 consecutive patients with bright liver absent-to-low
      alcohol consumption, no evidence of viral, genetic and autoimmune diseases, were
      compared to those of 60 age- and gender-matched historical controls without fatty
      liver by univariate and multiple logistic regression analysis. RESULTS: Patients
      were more often hypertriglyceridaemic, obese and diabetic than controls (p<.01).
      Mean values of alanine transaminase, gammaglutamyltranspeptidase, triglycerides,
      uric acid, fasting and log insulin, transferrin percent saturation and ferritin
      were significantly higher in the patients, while transferrin and quantitative
      insulin sensitivity check index, a quantitative insulin sensitivity index, were
      lower. No iron storage was found in those who underwent liver biopsy At
      univariate analysis the relative risk for non-alcoholic fatty liver disease
      significantly increased (p<0. 05) with increasing body mass index, fasting
      insulin, alanine transaminase, uric acid, triglycerides and
      gammaglutamyltranspeptidase; it decreased with increasing transferrin and
      quantitative insulin sensitivity check index. Multiple logistic regression
      analysis disclosed only fasting insulin and uric acid to be independent
      predictors of non-alcoholic fatty liver disease (p<0.05). CONCLUSIONS: Fasting
      insulin and serum uric acid levels indicating insulin resistance, but not indices
      of iron overload, are independent predictors of non-alcoholic fatty liver
      disease.

PMID- 11990394
TI  - Coeliac disease: foreword.

PMID- 11990395
TI  - Paediatric aspects of coeliac disease: old challenges and new ones...
AB  - The concept of coeliac disease has expanded from a gastrointestinal disease with
      malabsorption to a systemic immunological disease with a genetic basis.
      Epidemiological studies indicate that environmental factors, like the infant
      feeding pattern, affect the clinical presentation while population-screening
      studies indicate that the prevalence, at least in Caucasian populations, is
      similar. Secondary complications, like malignancies, osteopenia - osteoporosis,
      gynaecological and obstetrical problems and autoimmune diseases, are common. The
      risk is reduced or prevented by treatment with a gluten-free diet. The basis for
      such a secondary prevention is: 1. early case-finding by a) knowledge about
      different presentations of the disease and factors affecting that, b) generous
      serological testing in patients with vague symptoms, c) screening of risk groups,
      and, 2. support for children and adolescents with coeliac disease to comply with
      the gluten-free diet.

PMID- 11990396
TI  - Clinical features of coeliac disease.
AB  - Aim of this review is to describe the extremely variable clinical presentation of
      coeliac disease. Moreover due to these varying manifestations, "coeliac
      literature" is characterised by a very rich terminology, which has not been
      unified, so far To help readers, not familiar with that terminology, we have
      given an explanation for the most common coeliac terms.

PMID- 11990397
TI  - Coeliac disease and malignancy.
AB  - The development of malignancy, particularly lymphoma, is the most serious
      complication to affect patients with coeliac disease. Although the association
      has been known for about 40 years, there are still gaps in our understanding. The
      prevalence of lymphoma and why only some coeliac patients develop this are not
      clear but environmental and genetic factors must be at work. Based on data from a
      large coeliac clinic in Derby, about 55 lymphomas per year would arise in the
      coeliac population of the United Kingdom, of which half would affect the small
      bowel. Whether patients with coeliac disease who have atypical or no symptoms at
      diagnosis, are at the same risk as those who are diagnosed as a result of
      classical symptoms as was more the case in the past, is not known. Some patients,
      however do have coeliac disease and lymphoma diagnosed at the same presentation.
      This consideration has implications for initiating screening programmes to detect
      coeliac disease and thus offer patients a gluten-free diet early that would help
      to reduce the risk of lymphoma from developing. In this context, case-finding
      rather than blanket population screening is to be recommended on present
      evidence. Research into the role of intraepithelial lymphocytes in the genesis of
      lymphoma has indicated that non-responsive coeliac disease (refractory sprue) and
      ulcerative jejunoileitis (ulcerative jejunitis) are part of the lymphoma
      spectrum. The diagnosis of lymphoma can be difficult and the prognosis, in
      general, is poor, although with modern chemotherapeutic regimes and surgery in
      selected cases, long-term survival is possible. The best option is to try and
      prevent lymphoma from arising by advising all patients to adhere to a strict
      gluten-free diet. Malignant complications of coeliac disease are uncommon but
      will continue to challenge clinicians and clinical scientists. Unravelling the
      mechanisms that contribute to the development of lymphoma and other tumours in
      coeliac disease may well contribute to a wider understanding of oncogenesis.

PMID- 11990398
TI  - Coeliac disease--all questions answered?
AB  - Gliadin specific T cells in the small intestines of coeliac disease patients use
      the disease associated human leukocyte antigen-DQ2 molecules in their antigen
      recognition. In an exciting interplay with tissue transglutaminase, the immune
      system recognises modified gliadin peptides and mounts a phlogistic response.
      Moreover, the role for autoimmune phenomena and the mechanism of breaking of
      immunological tolerance remain elusive.

PMID- 11990399
TI  - Expanding the prospects of nephrology in the Balkan Peninsula: the spirit of the
      Balkan Cities Association of Nephrology, Dialysis, Transplantation, and
      Artificial Organs (BANTAO).

PMID- 11990400
TI  - Effects of peritoneal dialysis solutions on the secretion of growth factors and
      extracellular matrix proteins by human peritoneal mesothelial cells.
AB  - OBJECTIVE: To compare the effects of different peritoneal dialysis solutions
      (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming
      growth factor-beta1 (TGFbeta1), procollagen I C-terminal peptide (PICP),
      procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human
      peritoneal mesothelial cells (HPMC). DESIGN: Using M199 culture medium as
      control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate
      [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare,
      Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L
      bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P
      4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E);
      Baxter] were tested. Growth-arrested and synchronized HPMC were continuously
      stimulated for 48 hours by test PDS diluted twofold with M199, TGFbeta1 1 ng/mL,
      or different concentrations of icodextrin. VEGF, TGFbeta1, and fibronectin
      secreted into the media were analyzed by ELISA, and PICP and PIIINP by
      radioimmunoassay. RESULTS: Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E,
      significantly increased VEGF secretion compared with control M199. D 4.25- and P
      4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and
      P 1.5, respectively, suggesting that high glucose may be involved in the
      induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was
      significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting
      a role for glucose degradation products (GDP) in VEGF production. TGFbeta1
      secretion was significantly increased by D 4.25 and E. Icodextrin increased
      TGFbeta1 secretion in a dose-dependent manner. All PDS tested significantly
      increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced
      PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal
      4.25-induced PIIINP secretion was significantly higher than P 1.5, again
      implicating high glucose and GDP in PIIINP secretion by HPMC. There was no
      significant increase in PICP or fibronectin secretion using any of the PDS
      tested. Addition of TGFbeta1 1 ng/mL into M199 control significantly increased
      VEGF, PICP, PIIINP, and fibronectin secretion by HPMC. CONCLUSIONS: The present
      study provides direct evidence that HPMC can secrete VEGF, TGFbeta1, and PIIINP
      in response to PDS, and that HPMC may be actively involved in the development and
      progression of the peritoneal membrane hyperpermeability and fibrosis observed in
      long-term PD patients. This study also suggests that both high glucose and GDP in
      PDS may play important roles in inducing VEGF and PIIINP production/secretion by
      HPMC.

PMID- 11990401
TI  - Changes in peritoneal coagulation and fibrinolysis after discontinuation of
      chronic peritoneal dialysis.
AB  - OBJECTIVES: To study changes in peritoneal function after transfer from chronic
      peritoneal dialysis (CPD) to hemodialysis (HD), especially the effects on
      peritoneal coagulation, fibrinolytic markers, and mesothelium. DESIGN:
      Prospective observational study. SETTING: A tertiary-care university hospital.
      PATIENTS: Nine patients who transferred from CPD to HD were enrolled in the study
      after giving fully informed consent. METHODS: After transfer to HD, the
      peritoneal cavity was lavaged with low glucose PD solution once per day through
      PD catheters left in place. Thrombin-antithrombin III complex (TAT) was measured
      serially as a marker of peritoneal coagulation. As fibrinolytic markers,
      fibrinogen/fibrin degradation products (FDP) and plasmin-alpha2-antiplasmin
      complex (PIC) were assessed. Cancer antigen 125 (CA125) was measured as a marker
      of mesothelial cell mass. RESULTS: Levels of peritoneal TAT and FDP were much
      higher than plasma levels, indicating high local fibrin turnover. Transfer to HD
      induced a significant fall in mean peritoneal TAT, from 115.8 +/- 52.1 to 60.7 +/
      21.8 ng/mL, p < 0.05. Except for 1 patient with a 20-fold increase, mean
      peritoneal FDP decreased significantly, from 43.6 +/- 11.1 to 19.6 +/- 3.5
      microg/mL, p < 0.05. Mean peritoneal PIC increased significantly, from 1.9 +/-
      0.4 to 3.9 +/- 0.6 microg/mL, p < 0.05. Peritoneal CA125 increased from 156.4 +/-
      57.3 to 1426.2 +/- 389.4 U/mL, p < 0.05. CONCLUSIONS: Peritoneal fibrin turnover
      was accelerated on CPD and stabilized after transfer to HD. Transfer to HD also
      induced mesothelial regeneration.

PMID- 11990402
TI  - Patients' descriptions of specific factors leading to modality selection of
      chronic peritoneal dialysis or hemodialysis.
AB  - OBJECTIVES: There has been increasing interest in understanding how patients with
      chronic renal failure choose between chronic peritoneal dialysis (CPD) and
      hemodialysis (HD) for renal replacement therapy. The purpose of the present study
      was to examine the influences and specific factors that patients identify as
      significant in choosing a specific dialysis modality for treatment of their end
      stage renal disease (ESRD). PATIENTS AND DESIGN: 40 patients (20 CPD, 20 HD) who
      had started dialysis within the preceding 6 months were randomly selected to
      participate in the study. A structured interview was conducted with the patients,
      discussing and exploring what factors patients thought were important in helping
      them decide their treatment modality. The format of the interview was open-ended.
      Based on patients' comments, a taxonomy of the specific factors that influenced
      the patients' decisions was developed. SETTING: The study was conducted in a
      freestanding CPD unit and two freestanding HD units. RESULTS: All 20 CPD patients
      reported choosing their treatment modality; only 8 of the 20 HD patients reported
      having a choice of treatment modality. 18 of the 22 patients who participated in
      predialysis educational programs opted for CPD. 83% of the patients reported that
      their physician was important in influencing their treatment choice; however, the
      CPD patients relied more on written material and the opinions of their
      spouse/significant other or other family members in making their decisions.
      Issues of autonomy and control were important for 95% of patients choosing CPD.
      Both CPD and HD patients cited a variety of treatment-specific factors. The three
      most frequently cited reasons for choosing CPD were (1) flexibility of schedule
      (19 patients), (2) convenience of performing CPD in their own home (19 patients),
      and (3) the option of doing dialysis at night while sleeping (8 patients). The 8
      HD patients who selected their treatment modality cited the desirability of
      having a planned schedule (7 patients) and letting nurses or other take care of
      them (5 patients). CONCLUSIONS: The present study explored factors perceived by
      patients as being important in determining their choice of renal replacement
      therapy. A taxonomy of patient influences and concerns has been developed to
      provide caregivers with a framework to structure their educational strategies and
      assist patients with progressive renal failure in making an informed choice of
      therapeutic modality for their ESRD treatment.

PMID- 11990403
TI  - Large body mass index does not predict short-term survival in peritoneal dialysis
      patients.
AB  - OBJECTIVE: Higher than normal body mass index (BMI) is associated with an
      increased risk of death in the general population. We examined the effect of
      higher than normal BMI on patient and technique survival in peritoneal dialysis
      patients (PD), controlling for comorbidity, initial albumin, dialysate-to-plasma
      ratio of creatinine (D/P(Cr)), and initial urea clearance (Kt/V). DESIGN:
      Registry database. SETTINGS: Four dialysis centers. PATIENTS: Incident PD
      patients. METHODS: All data were collected prospectively. Demographics, BMI,
      serum albumin, D/P(Cr), and comorbidity using the Charlson Comorbidity Index
      (CCI) were determined at the start of PD. 104 patients with a high BMI (> 27)
      were matched to a control group of 104 patients with normal BMI (20-27) for age,
      gender, presence of diabetes, and CCI. Patient and technique survival were
      compared using Cox proportional hazards model. MAIN OUTCOME MEASURES: Patient and
      technique survival. RESULTS: The groups were of similar age (56.1 vs 56.7 years),
      sex (60% males in both groups), race (Caucasian 80% vs 86%), presence of diabetes
      (40% vs 37%), CCI score (5.4 in both groups), initial albumin (3.6 vs 3.5 g/dL),
      and D/P(Cr) (0.65 in both groups). Kaplan-Meier survival analysis showed similar
      2-year patient survival between large BMI (> 27) and control (20-27) groups
      (76.6% vs 76.1%). Two-year technique survival was also similar between the two
      groups (59.7% vs 66.8%). With Cox proportional hazards analysis, BMI was not a
      predictor of patient mortality or technique survival when controlling for initial
      albumin, D/P(Cr), and initial Kt/V. CONCLUSIONS: We conclude that a BMI above
      normal is not associated with any increased or decreased risk of death in
      patients on PD for 2 years.

PMID- 11990404
TI  - The impact of increasing the daytime dialysis exchange frequency on peritoneal
      dialysis adequacy and nutritional status of Chinese anuric patients.
AB  - OBJECTIVE: To study the effect of increasing the daytime dialysis exchange
      frequency on dialysis adequacy and nutritional status of Chinese anuric patients.
      SETTING: University teaching hospital. PATIENT: 100 anuric patients on continuous
      ambulatory peritoneal dialysis (CAPD). DESIGN: 50 patients had one additional
      daytime 2-L exchange (intervention group); the dialysis regimen remained
      unchanged in the other 50 patients (control group). OUTCOME: Dialysis adequacy
      [Kt/V, weekly creatinine clearance (wCCr), and net ultrafiltration (UF)] and
      nutritional status [serum albumin, dietary protein intake, represented by
      normalized protein nitrogen appearance (nPNA), and percent lean body mass (%LBM)]
      were measured at 0 and 6 months. RESULTS: Baseline dialysis adequacy and
      nutritional indices were comparable between the two groups. In the control group,
      all parameters remained stable at month 6. In the intervention group, there were
      significant increases in UF, Kt/V, wCCr, nPNA, and %LBM from months 0 to 6. The
      improvement in nPNA was affected by daily exchange volume. In 30 patients, the
      number of exchanges was increased from 3 to 4 per day; their Kt/V and nPNA rose
      significantly from month 0 to month 6. In the other 20 patients, the number of
      exchanges was increased from 4 to 5 per day; there was a significant increase in
      Kt/V but nPNA remained static. The change in nPNA correlated inversely with Kt/V
      at month 0 (Pearson's r = -0.352, p = 0.012). Multivariate analysis with a
      general linear model showed that age, Kt/V at month 0, and 3 dialysis exchanges
      per day at month 0 (versus 4 exchanges) were independent predictors of the change
      in nPNA. CONCLUSIONS: Increasing the number of peritoneal dialysis exchanges
      effectively increased Kt/V in Chinese anuric CAPD patients. However, the
      improvement in nPNA correlated inversely with baseline Kt/V. Although increasing
      the number of exchanges from 3 to 4 per day improved nPNA, increasing the number
      of daily exchanges beyond 4 may not improve nPNA further.

PMID- 11990405
TI  - Normal or low initial PTH levels are not a predictor of morbidity/mortality in
      patients undergoing chronic peritoneal dialysis.
AB  - OBJECTIVE: During the past few decades, the pattern of bone disease in uremic
      patients has changed significantly. There has been an increase in the number of
      patients with normal or low initial parathyroid hormone (PTH) levels,
      particularly in patients on chronic peritoneal dialysis (CPD). Previous authors
      have described a higher prevalence of bone pain, microfractures, and fractures,
      and higher mortality among these patients. The aim of this study was to determine
      the incidence, morbidity, and mortality of patients who had a low or normal
      intact PTH (iPTH) level when they started CPD. DESIGN: We reviewed the records of
      251 patients in our program that started CPD during the past 5 years (January
      1996-December 2000). Clinical data, laboratory variables, medication, and
      dialysis parameters/dose were available at every clinic visit (approximately
      every 4 weeks). Intact PTH was used to express parathyroid function; values 3
      times higher than the upper limit of normal (ULN) were assumed to be optimal.
      Variables predictive of the development of parathyroid dysfunction were
      calculated by univariate and multivariate logistic regression analysis. RESULTS:
      Of the patients who started CPD, 15.5% had iPTH values below the ULN (7.6
      pmol/L), and an additional 29.5% had an iPTH of less than 3 times the ULN (i.e.,
      between 7.6 and 22.8 pmol/L). We call these two groups of patients the normal/low
      initial iPTH group. During the follow-up period (3-63 months), we found a trend
      toward increasing iPTH levels. By the end of the study period, 61.2% of those
      with normal/low initial iPTH remained in the normal/low iPTH range, and 38.8% had
      converted to a group with an iPTH range higher than 22.8 pmol/L. The patients who
      converted their iPTH grouping were younger, fewer of them were diabetics (p = not
      significant), and they were more frequently on low calcium dialysate (p < 0.05).
      Hyperphosphatemia was an independent risk factor for subsequent iPTH changes
      during the course of continuous ambulatory PD treatment. All patients in the
      normal/low iPTH groups had a low prevalence of bone fractures (3.5%). Also,
      patients who remained in the normal/low iPTH group at the end of the follow-up
      period did not have more fractures than those who converted to the
      hyperparathyroid group (3.8% vs 3.1%). We found no differences in bone fractures
      between patients with iPTH levels below 22.8 and those with levels above 22.8
      pmol/L (3.5% vs 5.4%), nor were there differences in patient and technique
      survival between these two groups. CONCLUSION: Normal/low initial iPTH is a
      frequent finding among patients starting CPD. Serum phosphorus was an independent
      risk factor for subsequent iPTH changes during the course of CPD treatment. Use
      of low calcium dialysate was significantly higher in patients who converted their
      iPTH into the high iPTH range. Very few patients with low/normal iPTH had bone
      related symptoms (pain and fractures), and their morbidity and mortality did not
      differ from those patients with a high initial iPTH level.

PMID- 11990406
TI  - A prospective randomized study of the effect of a subcutaneously "buried"
      peritoneal dialysis catheter technique versus standard technique on the incidence
      of peritonitis and exit-site infection.
AB  - OBJECTIVE: A new method for implantation of peritoneal dialysis (PD) catheters
      was described in 1991. The distal part of the catheter is buried subcutaneously
      and exteriorized at the start of PD. This study was designed to evaluate the
      effect of such a subcutaneous rest period on the incidence of peritonitis and
      exit-site infections (ESI). DESIGN: Sixty patients were randomized to either the
      new method (B group; n = 30) or to not having the distal part buried
      subcutaneously (NB group; n = 30). Sixty-five patients (NS group) were not
      randomized as they had to start PD within 1-2 weeks after implantation. The
      Moncrief-Popovich catheter was used in the B and NB groups and a standard
      Tenckhoff catheter was used in the NS group. PATIENTS: Patients scheduled for PD
      treatment, judged not in need of PD for at least 6 weeks after implantation.
      RESULTS: There was no statistically significant difference in the cumulative
      probability of not developing peritonitis during the first 6, 12, and 24 months.
      The incidence of the first episode of peritonitis was 1/40, 1/26, and 1/33
      treatment-months in the B, NB, and NS groups, respectively. The incidence of ESI
      was 1/103 and 1/95 treatment-months in the B and NS groups, respectively. The
      cumulative probability of not developing ESI was similar in both groups. There
      were no episodes of ESI in the NB group. The difference in the number of ESI
      between the NB and NS groups was significant (p < 0.05). CONCLUSIONS:
      Subcutaneous burying of the distal catheter segment prior to starting PD does not
      reduce the risk of contracting peritonitis or exit-site infection.

PMID- 11990407
TI  - Alterations in lipoprotein composition in peritoneal dialysis patients.
AB  - OBJECTIVE: Dyslipidemia is common among patients with end-stage renal disease,
      whether treated by hemodialysis (HD) or peritoneal dialysis (PD). To better
      understand the specific lipoprotein abnormalities in PD patients, we measured the
      lipid and apolipoprotein (Apo) composition of the four major classes of plasma
      lipoproteins in PD patients, HD patients, and healthy control subjects: very low
      density (VLDL), intermediate density (IDL), low density (LDL), and high density
      lipoproteins (HDL). DESIGN: Fasting plasma samples were obtained from 15
      nondiabetic PD patients, 15 nondiabetic HD patients, and 16 healthy control
      subjects, all from a cross section of patients and subjects in the region of
      Goteborg, Sweden. Lipoproteins were isolated by preparative ultracentrifugation,
      and lipid and apolipoprotein concentrations were measured by gas chromatography
      and electroimmunoassay, respectively. RESULTS: Alterations in lipoprotein
      composition were apparent in all four lipoprotein density classes from PD and HD
      patients. VLDL contained a significantly higher concentration of ApoCIII in both
      HD and PD patients, and an elevation of free cholesterol, triglyceride, ApoB,
      ApoCII, and ApoE in PD patients. IDL from both PD and HD patients contained an
      excess of free and esterified cholesterol and triglyceride and significantly
      elevated levels of ApoB, ApoCII, ApoCIII, and ApoE. LDL had a higher
      concentration of ApoB in PD patients and elevated triglyceride and ApoCIII in
      both PD and HD patients. HDL isolated from PD patients had lower free cholesterol
      and ApoAI levels compared to control subjects, but these were not significantly
      different from HD patients. CONCLUSIONS: An increase in lipid and apolipoprotein
      mass in IDL, and an enrichment of ApoCIII in VLDL, IDL, and LDL were observed in
      both HD and PD patients. The predominant alteration in lipoprotein composition
      distinguishing PD patients from HD patients was an elevation of ApoB in LDL.
      Further study of these alterations in lipoprotein composition in PD patients will
      be helpful in understanding the underlying causes of dyslipidemia and,
      ultimately, to the selection of hypolipidemic drugs or other treatments to reduce
      the cardiovascular risks associated with dyslipidemia in these patients.

PMID- 11990408
TI  - The relationship between ultrafiltrate volume with icodextrin and peritoneal
      transport pattern according to the peritoneal equilibration test.
AB  - OBJECTIVE: To establish a relationship between peritoneal transport membrane
      pattern, analyzed by the peritoneal equilibration test (PET), and drained volume
      using icodextrin (7.5% Ico) and glucose (3.86% Glu) solutions. DESIGN: Thirty
      peritoneal dialysis patients were submitted to a standard 4-hour PET and divided
      into 4 transport categories based on dialysate-to-plasma ratio of creatinine
      (D/Pcr) and dialysate ratio of glucose at 4 and zero hours of the dwell (D4/D0).
      Patients were asked to perform exchanges for 2 consecutive nights in 10-hour
      dwells (2 L 3.86% Glu solution on the first night, and 2 L 7.5% Ico solution on
      the second night). The drained volume was measured and dialysate samples from the
      overnight exchanges were obtained for beta2-microglobulin (B2M) levels. RESULTS:
      PET classification using D/Pcr showed that 46.6% of the patients were high and
      high-average transporters, or 23.3% when D4/D0 was used. In spite of this
      difference, both methods showed significant correlation (p = 0.0001, r = 0.862).
      The mean drained volumes were similar for both solutions (for 3.86% Glu, 2696 +/-
      369 mL; for 7.5% Ico, 2654 +/- 424 mL). The high and high-average transport
      patients classified by D4/D0 achieved a higher ultrafiltration with 7.5% Ico than
      with 3.86% Glu (p = 0.0235). When classified by D/Pcr, the difference was not
      significant (p = 0.2243). In the low and low-average transport patients
      classified by D/Pcr, we observed a significantly lower ultrafiltration when 7.5%
      Ico was used compared to 3.86% Glu solution (p = 0.0197). Using D4/D0, we saw a
      tendency toward lower ultrafiltration (p = 0.0719) in the same group. We then
      correlated the PET results and the difference between drained volume with 7.5%
      Ico and 3.86% Glu solution [deltaV (I-G)]. We found a significant negative
      correlation between D4/D0 and deltaV (I-G) (p = 0.002, r = -0.5390), and a
      positive correlation between D/Pcr and deltaV (I-G) (p = 0.005, r = 0.4932). The
      levels of B2M obtained with 7.5% Ico were higher than those obtained with 3.86%
      Glu solution (for 7.5% Ico, 9.47 +/- 6.71 microg/vol; for 3.86% Glu, 7.29 +/-
      4.91 microg/vol; p = 0.004). Furthermore, we found significant correlation
      between the total amount of B2M obtained with 7.5% Ico solution and D4/D0 (p <
      0.0001, r = -0.4493), and D/Pcr (p < 0.0001, r = 0.5431). CONCLUSION: Mean
      drained volume was similar between the two solution groups. High transporters, as
      defined by D4/D0, achieved higher ultrafiltration with 7.5% Ico than with 3.86%
      Glu solution. This is most likely due to the higher number of small pores in the
      peritoneal membrane. Low transporters, as classified by D/Pcr, achieved lower
      ultrafiltration with 7.5% Ico than with 3.86% Glu solution. The deltaV (I-G) and
      the PET results showed significant correlation, confirming that high transporters
      have a higher ultrafiltration volume with 7.5% Ico. The total B2M mass obtained
      with 7.5% Ico was greater than with 3.86% Glu solution and significantly higher
      in the high transport patients, indicating a larger number of small pores. Thus,
      the deltaV (I-G) could give us an idea of the peritoneal transport pattern in
      peritoneal dialysis patients.

PMID- 11990409
TI  - Methodological issues in assessing the incidence of peritoneal dialysis
      associated peritonitis in children.
AB  - OBJECTIVES: To evaluate the distribution of peritonitis incidence and assess the
      usefulness of patient-specific peritonitis rates in children. DESIGN: 49 children
      on automated peritoneal dialysis (PD) followed during a 2-year observation
      period. SETTING: Single-center, academic children's hospital. PATIENTS: 49
      children aged 2 months to 18 years; 24 prevalent, 25 incident during the
      observation period. Cumulative observation time was 639 patient-months. MAIN
      OUTCOME MEASURES: Cohort-specific peritonitis incidence, median patient-specific
      peritonitis incidence, mean peritonitis incidence by gamma-Poisson (negative
      binomial) modeling, peritonitis-free survival by Kaplan-Meier life-table
      analysis. RESULTS: 68 new peritonitis episodes and 21 relapses occurred in 27
      patients. The distribution of patient-specific peritonitis incidence was bimodal,
      with a large group experiencing no or very few episodes, and another cluster
      around 1 episode per 6-9 months. Overall cohort-specific peritonitis incidence
      was 1.28, median subject-specific incidence 0.99, and mean incidence according to
      negative binomial modeling 1.04 (95% confidence interval 1.02-1.06) episodes per
      patient-year. Median peritonitis-free survival time was 6.9 months. In those
      patients who developed peritonitis, subject-specific peritonitis incidence was
      inversely correlated with patient age (r = -0.42, p < 0.05) and duration of
      chronic PD at last observation (r = -0.42, p < 0.05). CONCLUSIONS: Since the
      distribution of peritonitis in children is non-Gaussian, the average risk of
      peritonitis is more accurately expressed by the median of the individual subject
      specific peritonitis rates or by the mean incidence estimate obtained by the
      negative binomial distribution model. The assignment of a personal peritonitis
      risk to each patient permits risk factor analysis by routine statistical methods,
      even in smaller populations.

PMID- 11990410
TI  - Peritoneal dialysis retardation of progression of advanced renal failure.
AB  - OBJECTIVES: The rate of decline of residual renal function is slower in
      peritoneal dialysis (PD) than in hemodialysis. However, it is unclear which and
      whether either of the two techniques modifies the natural course of renal
      failure. We tested whether PD influences the natural course of the progression of
      chronic renal failure in humans. DESIGN: Retrospective review of clinical charts.
      SETTING: Tertiary-care center. PATIENTS: Fourteen patients were selected from the
      36 patients that were treated with PD in our center from January 1997 to June
      2000, applying the following criteria: predialysis follow-up longer than 12
      months, renal creatinine clearance 20 mL/minute or more at the start of
      predialysis follow-up, follow-up while on PD longer than 6 months, and renal
      creatinine clearance above 0 mL/minute at the start of PD. MAIN OUTCOME MEASURE:
      Residual renal function calculated as renal creatinine clearance obtained from 24
      hour urine samples. RESULTS: A lower mean rate of decline of residual renal
      function was observed during PD than during the predialysis period (-0.06 +/-
      0.16 vs -0.94 +/- 0.74 mL/min/month, p < 0.0005). The rate of decline in renal
      creatinine clearance was faster in every patient during the predialysis period
      than during his or her time on PD. CONCLUSIONS: These preliminary data support
      the hypothesis that PD may contribute to the slowing of the natural progression
      of renal disease in humans, as it does in rodents. Prospective studies involving
      a larger number of patients are needed to settle the question.

PMID- 11990411
TI  - Peritoneal dialysis in Asia in the 21st century: perspectives on and obstacles to
      peritoneal dialysis therapy in Asian countries.

PMID- 11990412
TI  - What factors contribute to differences in the practice of peritoneal dialysis
      between Asian countries and the West?
AB  - To study variations in the practice of peritoneal dialysis within Asia and
      between Asia and the West, relevant information was collected through
      questionnaires from nephrologists in several Asian countries and by a literature
      search. Data indicate that economy significantly affects dialysis treatment
      rates. Peritoneal dialysis was often underutilized. The effect of Kt/V on
      survival was less obvious compared to the West in countries where peritoneal
      dialysis patient survival rates were high. More cost-effective dialysis regimes
      should be developed to increase dialysis treatment rates.

PMID- 11990413
TI  - Peritoneal dialysis in Asia: an external perspective.
AB  - There are almost 30,000 patients maintained on peritoneal dialysis (PD) in Asia,
      representing about 8% of all Asian dialysis patients. The largest numbers of PD
      patients are in Japan and China, but the highest PD penetration is in Hong Kong,
      Korea, and Singapore. Notable features of PD in Asia include the varying rates of
      use across the different countries. The reasons for this are reviewed here, with
      particular emphasis on the significance of whether dialysis providers are
      predominantly private or public. The excellent rates of both patient and
      technique survival in the richer Asian countries are also examined and
      interpreted in the context of recent data showing that Asian patients living in
      North America have generally superior survival on dialysis and better compliance
      with PD than their Caucasian counterparts. It is concluded that the healthier
      baseline health status in South East Asian patients, in particular, contributes
      to their impressive outcomes. The approach to both clearance and ultrafiltration
      is less aggressive in Asian countries than in the West. Studies looking at the
      relationship between clearance and clinical outcome in Asia are reviewed and it
      is concluded that the benefits of higher clearances have been harder to show than
      in North America because of the relatively better outcomes of the patients. The
      concern about sclerosing encapsulating peritonitis in Japan particularly is
      emphasized. The Hong Kong model of dialysis delivery with its high use of PD and
      the arguments for and against it are also reviewed.

PMID- 11990414
TI  - The role of vascular endothelial growth factor in peritoneal hyperpermeability
      during CAPD-related peritonitis.

PMID- 11990415
TI  - Simplified percutaneous placement of peritoneal dialysis catheters: comparison
      with surgical placement.

PMID- 11990416
TI  - Changes in erythrocyte Ca2+, K+, and Mg2+ content in uremic patients on CAPD.

PMID- 11990417
TI  - Tidal peritoneal dialysis during pregnancy improves clearance and abdominal
      symptoms.

PMID- 11990418
TI  - Re-establishment of flow in peritoneal dialysis catheters using the endoluminal
      FAS brush.

PMID- 11990419
TI  - Obstruction of the peritoneal catheter caused by cryoglobulin precipitation.

PMID- 11990420
TI  - Spontaneous peritoneal catheter extrusion.

PMID- 11990421
TI  - Hiccups in a CAPD patient treated with standard solution: improvement with the
      use of a neutral pH dialysis solution.

PMID- 11990422
TI  - A possible baclofen-induced neurotoxicity in a CAPD patient who recovered with
      long-duration hemodialysis.

PMID- 11990424
TI  - Literature: March-April 2002.

PMID- 11990423
TI  - Least publishable units and publication costs.

PMID- 11990425
TI  - Microbial transformation of danazol.
AB  - Danazol (17beta-hydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d] isoxazole) (1) on
      fermentation with Fusarium lini, Aspergillus niger, and Cephalosporium aphidicola
      yielded 17beta-hydroxy-2-(hydroxymethyl)-17-alpha-pregn-4-en-20-yn-3-one (2) and
      17beta-hydroxy-2-(hydroxymethyl)-17 alpha-pregna-1,4-dien-20-yn-3-one (3), while
      the fermentation of 1 with Bacillus cerus yielded compound 2 only.

PMID- 11990426
TI  - Relationships between molecular properties and antimycobacterial activities of
      steroids.
AB  - Progesterone (1), cholesterol (2), stigmasterol (3), ergosterol endoperoxide (4),
      sitosterol (5), betulin (6), fusidic acid (7), chondrilasterol (8), and
      ergosterol (9) have been evaluated against Mycobacterium tuberculosis H37Rv. The
      maximum antimycobacterial activity seemed to depend on hydrophobicity and the
      type of substituents on the phytyl moiety on steroidal backbone. The variation in
      activity was rationalized using quantitative structure-activity relationship
      (QSAR) models based on several molecular descriptors including van der Waals
      surface area (VDW(A)), van der Waals volume (VDW(v)), polarizability, dipole
      moment, logP, and the differences between the Highest Occupied Molecular Orbital
      and the Lowest Unoccupied Molecular Orbital (HOMO-LUMO gap). The proposed QSAR
      models could be developed to predict the antimycobacterial activity of
      structurally similar steroids and to create a priority list for testing so that
      time, money, and effort can be focused on the potentially most promising
      steroids. The implications of QSAR data for the rational design of new
      antituberculosis agents are discussed. Because mycobacteria degrade steroids to
      progesterone-type compounds, unambiguous assignments of the high-field proton
      (1H) and carbon-13 (13C) NMR data of progesterone (1) were achieved through a
      combination of modern one- and two-dimensional (2D) NMR techniques.

PMID- 11990427
TI  - A new naphthoquinone from Polygonum aviculare.
AB  - A new naphthoquinone, 6-methoxyplumbagin was isolated from the acetone extracts
      of Polygonum aviculare. Its structure was elucidated by various spectroscopic
      methods. The known compounds sitosterol, oleanolic acid and 5,6,7,4'
      tetramethoxyflavanone were also obtained from this natural source.

PMID- 11990428
TI  - Isolation of two new ionone glucosides from quince (Cydonia oblonga Mill.)
      leaves.
AB  - The 9-O-beta-D-glucopyranosides of (6R)-3-oxo-4-hydroxy-7,8-dihydro-alpha-ionol 1
      and 3-oxo-5,6-epoxy-beta-ionol 2 were isolated from quince leaves. The glycosidic
      extract was obtained by XAD-2 adsorption and MeOH elution. After DCCC separation
      and flash chromatography, purification by high performance liquid chromatography
      was carried out. The novel quince leaf constituents were characterized as
      peracetates 1a and 2a.

PMID- 11990429
TI  - MAP: microwave-assisted extraction of cockroaches.
AB  - A Microwave-Assisted Process (MAP is a Trade-Mark of Her Majesty the Queen in
      Right of Canada as represented by the Minister of the Environment) solvent
      extraction procedure was used in conjunction with GC-MS analysis to investigate
      the chemical composition of dried and live cockroaches. The main components
      extracted were classified into four groups: sterols. fatty acids and their
      esters, long chain alkanes and fused aromatic hydrocarbons.

PMID- 11990430
TI  - Tri-nordammarane triterpenoids and neoclerodane diterpenoids from Salvia aspera
      (Labiatae).
AB  - From the aerial parts of Salvia aspera one new tri-nordammarane named amblyol (1)
      was isolated besides amblyone (2). An X-ray analysis was performed on compound 1.
      In addition, three known neoclerodane diterpenoids were also isolated. The
      structures of these compounds were established by spectral and chemical methods.
      The presence of dammarane triterpenoids in a Mexican Salvia is described for the
      first time.

PMID- 11990431
TI  - Aculeoside I, a novel 18,19-seco-ursane saponin isolated from Ilex aculeolata.
AB  - A novel 18,19-seco-ursane saponin, aculeoside I (1), in addition to four known
      saponins were isolated from the leaves of Ilex aculeolata Nakai and identified by
      using spectroscopic and chemical methods. The structure of the new saponin was
      established as 3,19-dihydroxyl-16,21-epoxy-18,19-seco-13(18)-urs-ene-28-oic-acid
      19-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranoside.

PMID- 11990432
TI  - New triterpenoids from the orchids Scaphyglottis livida and Nidema boothii.
AB  - Two new triterpenoids, nidemin (1), a modified lanostane, and 9,19-cyclolanosta
      24,24-dimethyl-25-en-3beta-yl trans-p-hydroxycinnamate (2) have been isolated
      from the orchids Nidema boothii and Scaphyglottis livida, respectively. The
      isolates were characterized by spectral methods. The structure of nidemin (1) was
      unambiguously confirmed by X-ray analysis.

PMID- 11990433
TI  - 3,4-Dihydroxy-7,8-dihydro-beta-ionone 3-O-beta-D-glucopyranoside and other
      glycosidic constituents from apple leaves.
AB  - 3,4-Dihydroxy-7,8-dihydro-beta-ionone 3-O-beta-D-glucopyranoside 1 has been
      isolated from a methanolic extract of apple (Malus domestica) leaves by XAD-2
      adsorption chromatography and subsequent purification by high speed
      countercurrent chromatography (HSCCC) and HPLC. Under acidic conditions this
      glycoside gives rise to a number of volatile compounds including 1,1,6-trimethyl
      1,2-dihydronaphthalene (TDN) 2, which is known as an off-flavor compound in wine.
      In the course of the study, six additional glycoconjugates were isolated from
      apple leaves, i.e. roseoside 3, 3-oxo-alpha-ionol beta-D-glucopyranoside 4,
      benzoic acid beta-D-glucose ester 5, kaempferol 3-O-rhamnoside 6, (+)
      syringaresinol beta-D-glucopyranoside 7 and 4-hydroxy-5-(3''-methyl-2''-butenyl)
      benzoic acid methylester 3-beta-D-glucopyranoside 8. The latter compound has been
      isolated for the first time in nature. In order to avoid the 'kerosene-off
      flavor' caused by TDN, the methanolic extract has been subjected to yeast
      fermentation. This treatment reduced the amount of TDN formed and resulted in an
      improved flavor impression of the methanolic extract.

PMID- 11990434
TI  - In vivo and in vitro production of alkaloids by Haplophyllum patavinum.
AB  - A protocol for shoot induction from callus of Haplophyllum patavinum was
      established. Two known furoquinoline (skimmianine and haplopine), and three
      quinolone (edulinine, ribalinine and isoplatydesmine) alkaloids were isolated for
      the first time from plant material, callus and shoot cultures of this species.
      The structures of these compounds have been characterised on the basis of
      spectroscopic evidence.

PMID- 11990435
TI  - Clinical and radiographic evaluation of periodontal intrabony defects treated
      with guided tissue regeneration. A pilot study.
AB  - BACKGROUND: The aim of this clinical and radiographic study was to evaluate the
      effect of guided tissue regeneration using a bioabsorbable barrier in the
      treatment of intrabony defects in humans. METHODS: Intrabony osseous defects (2
      or 3 walls) around mandibular canines and premolars were treated in 10
      systemically healthy patients with ages ranging from 35 to 56 years. Prior to the
      surgical phase, patients were enrolled in a strict maintenance program including
      oral hygiene instructions and scaling and root planing (presurgical Pi and GI <
      10%). Patients were seen for professional prophylaxis during the duration of the
      study. Clinical measurements were performed with an electronic probe at baseline
      and at reentry 8 months following surgical therapy. Measurements included
      clinical attachment levels (CAL), gingival margin levels (GML), probing depths
      (PD), bone defect levels (BDL), and alveolar crest level (ACL). A split mouth
      design was used. Quadrants were randomly assigned for treatment by GTR
      (experimental) or open flap debridement alone (control). Standardized radiographs
      were taken at baseline and at reentry. Digital images were analyzed by
      subtraction to assess changes in area (A) and optical density (OD). Data were
      evaluated using paired t test. RESULTS: Statistically significant differences
      were found in both groups when comparing baseline and post-treatment values for
      CAL, GML, PD, and BDL (P < 0.0 1). Greater reductions in BDL and gain in A and OD
      were observed in the GTR group when compared to control (P < 0.01). Both
      therapies were effective in improving the clinical parameters assessed.
      CONCLUSION: Clinical and radiographic findings from this study demonstrated more
      bone fill in sites treated with GTR.

PMID- 11990436
TI  - Subgingival microbiota of Brazilian subjects with untreated chronic
      periodontitis.
AB  - BACKGROUND: Different periodontopathogenic microbiota have been associated with
      periodontal diseases in several populations. The present investigation determined
      the subgingival microbiota of untreated chronic periodontitis Brazilians using
      the checkerboard DNA-DNA hybridization technique. METHODS: Twenty-five
      periodontitis patients (mean age, 41 +/- 2; mean probing depth [PD], 3.3 +/- 0.2;
      mean attachment level [AL], 3.6 +/- 0.2) with no history of previous periodontal
      therapy and a control group of 14 healthy subjects (mean age, 34 +/- 0.6; mean
      PD, 1.8 +/- 0.2; mean AL, 1.7 +/- 0.1) were selected. Measurements of PD, AL,
      bleeding on probing, plaque accumulation, and suppuration were recorded at 6
      sites/tooth. Subgingival plaque samples were obtained from 4 sites in each
      tooth/subject in both groups. The presence and levels of 41 subgingival species
      were determined in 4,032 plaque samples using whole genomic DNA probes and the
      checkerboard method. RESULTS: Periodontal pathogens, as well as some unusual
      species (E. faecalis, E. coli and Bartonella sp.), were detected significantly
      more often and/or in higher levels in the periodontitis group (P < 0.05). Most
      species were more frequently detected in interproximal sites. B. forsythus, P.
      gingivalis, E. nodatum, and F. nucleatum ss vincentii showed a significant
      positive correlation with mean PD and AL (P < 0.05). CONCLUSIONS: The subgingival
      microbiota of Brazilians with untreated chronic periodontitis were complex,
      including high proportions of periodontopathogens commonly found in other
      populations, as well as some unusual species.

PMID- 11990437
TI  - Root surface morphological changes after focused versus defocused CO2 laser
      irradiation: a scanning electron microscopy analysis.
AB  - BACKGROUND: Many studies have observed damages to root surfaces treated by CO2
      laser in continuous mode with a focused beam. The morphologic changes observed
      were always associated with temperature increase induced by high energy release.
      METHODS: The purpose of this study was to analyze by scanning electron microscopy
      (SEM) the effects of CO2 laser in 2 different modes on root surfaces. Study
      samples consisted of 30 extracted single-rooted periodontally compromised human
      teeth. Root specimens were randomly assigned to 3 groups: group A (12) treated
      with CO2 laser in continuous mode with a focused beam of 0.8 mm; group B (12)
      treated with CO2 laser in pulsed mode with defocused beam of 4 mm; and group C
      (6), untreated controls. RESULTS: Group A (continuous mode) showed severe damages
      to dentin surfaces such as craters and fissures. Group B (defocused mode) did not
      result in any damages to the root surfaces, showing flat and smooth surfaces with
      apparent fusion of the smear layer and dentinal tubules almost completely sealed.
      The untreated control group was characterized by irregular and amorphous surfaces
      with several shallow depressions. CONCLUSIONS: Although both laser modes resulted
      in changes to the treated root surface specimens, the changes resulting in a
      smooth surface from use of defocused pulsed beam may present an advantage in
      periodontal treatment.

PMID- 11990438
TI  - Endoscopic visualization of the submarginal gingiva dental sulcus and tooth root
      surfaces.
AB  - BACKGROUND: Direct, real-time visualization of the hard and soft tissues within
      the gingival sulcus may aid the clinician in diagnosis and therapy of periodontal
      disease. This report describes an endoscope specifically designed for this
      purpose and the interpretation of dental endoscopic images. METHODS: Medical
      endoscope technology was modified for application in the dental environment. A
      fixed, fused fiber optic bundle, less than 1 millimeter in diameter, was coupled
      to an active matrix LCD-TFT flat panel video monitor for viewing by the
      clinician. A bilumen sheath was designed to provide irrigation of the sulcus and
      a sterile barrier between the patient and the fiber bundle. Standard dental
      curets and ultrasonic scalers were adapted for instrumentation aided by the
      endoscope. RESULTS: Endoscope technology has been successfully adapted for use in
      periodontal diagnosis and therapy. Techniques for identification and
      interpretation of the hard and soft tissue images, as well as the location of
      root deposits and caries, have been developed. CONCLUSIONS: The dental endoscope
      gives the clinician direct, real-time visualization and magnification of the
      subgingival tooth root surface, aiding in the location of deposits on the tooth
      root. The subgingival soft tissue, including the gingival attachment, sulcus
      wall, and sulcus contents, can be assessed. Identification and location of
      subgingival caries, root fractures, tooth root deposits, post perforations, and
      open restoration margins may aid the clinician in diagnosis and therapy.

PMID- 11990439
TI  - Effect of estrogen deficiency on skeletal and alveolar bone density in sheep.
AB  - BACKGROUND: This study provides a longitudinal assessment of changes in alveolar
      and skeletal bone mineral density (BMD) in ovariectomized animals. METHODS:
      Following ovariectomy (OVX) (n = 6) or sham-operation (n = 6) intraoral
      radiographs were made at 4-month intervals and serum 17-beta-estradiol,
      osteocalcin, and interleukin (IL)-6, urinary deoxypyridinium, and salivary IL-6,
      deoxypyridinium, and osteocalcin concentrations were evaluated. Twelve months
      after surgery, animals were sacrificed and the mandible and radius/ulna removed.
      Bones were sectioned and radiographed. Mean BMD and cortical thicknesses were
      calculated from each region. RESULTS: OVX animals had a progressive decrease in
      serum 17-beta-estradiol, increased serum osteocalcin and IL-6, urinary
      deoxypyridinium and salivary IL-6, osteocalcin and deoxypyridinium (P < 0.001),
      suggesting that they were becoming osteoporotic. The BMD of the radius/ulna and
      mandibular alveolar bone was significantly reduced in OVX animals (P < 0.05 and P
      < 0.001, respectively). Reduced alveolar bone BMD became evident in OVX animals 6
      months after surgery and became more severe during the subsequent 6 months.
      Alveolar crestal height was also significantly reduced in OVX animals (P <
      0.001). These biochemical and density changes preceded a significant reduction in
      serum 17-beta-estradiol, which occurred between 4 and 8 months following surgery.
      CONCLUSIONS: Serial measurements of alveolar BMD predicts loss of skeletal BMD in
      OVX sheep. Changes in alveolar BMD precede estrogen deficiency, suggesting that
      early signs of reduced BMD may be detected in peri-menopausal women. The presence
      of biomarkers of bone metabolism within saliva and their correlation with reduced
      BMD suggests that saliva could be used as an adjunct screening method for
      assessment of skeletal bone density.

PMID- 11990440
TI  - Human gingival fibroblasts produce nitric oxide in response to proinflammatory
      cytokines.
AB  - BACKGROUND: Although nitric oxide (NO) synthesis is increased in periodontal
      disease (PD), little is known about the possible sources of production by
      gingival tissues. In fact, gingival tissues from patients with periodontitis
      demonstrate greater levels of inducible nitric oxide (iNOS) expression than
      healthy tissue. Macrophages are the source of the iNOS expression, with
      endothelial cells also contributing. In the present study, our hypothesis has
      been that human gingival fibroblasts (HGF) also have the ability to produce NO.
      We have established for the first time that HGF express increased levels of iNOS
      and modulate NO synthesis in response to proinflammatory cytokines that act
      synergistically. METHODS: NO production under basal conditions or following
      incubation with tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta, and
      interferon (IFN)-gamma was assessed by measurement of stable NO metabolites,
      nitrite, and nitrate, in a microplate adaptation of the Griess assay. Total RNA
      was isolated from HGF for determination of iNOS mRNA levels. RESULTS: We have
      shown that NO production is elevated in HGF that are stimulated simultaneously by
      TNF-alpha, IL-1beta, and IFN-gamma. Northern blot analysis confirmed that the
      production of iNOS mRNA by HGF is upregulated in the presence of these cytokines.
      Addition of mercaptoethyl guanidine (MEG), a specific inhibitor of iNOS,
      profoundly reduced the production of NO in HGF. Non specific inhibitors of iNOS,
      L-NG-monomethyl arginine (L-NMMA), and L-arginine-methyl ester (L-NAME) had
      little or no effect on NO produced in HGF. CONCLUSIONS: These results suggest
      that elevated NO production could be important in the pathogenesis of PD, and
      also suggest the ability of an iNOS inhibitor to modulate the disease. Treatments
      with drugs to block the production of nitric oxide or block its effects might be
      therapeutically valuable.

PMID- 11990441
TI  - Clinical evaluation of an enamel matrix protein derivative combined with a
      bioactive glass for the treatment of intrabony periodontal defects in humans.
AB  - BACKGROUND: The purpose of the present study was to compare the treatment of deep
      intrabony defects with a combination of an enamel matrix protein derivative (EMD)
      and a bioactive glass (BG) to BG alone. METHODS: Twenty-eight patients with
      chronic periodontitis, each of whom displayed 1 intrabony defect, were randomly
      treated with a combination of EMD and BG or with BG alone. Soft tissue
      measurements were made at baseline and at 1 year following therapy. RESULTS: No
      differences in any of the investigated parameters were observed at baseline
      between the 2 groups. Healing was uneventful in all patients. At 1 year after
      therapy, the sites treated with EMD and BG showed a reduction in mean probing
      depth (PD) from 8.07 +/- 1.14 mm to 3.92 +/- 0.73 mm and a change in mean
      clinical attachment level (CAL) from 9.64 +/- 1.59 mm to 6.42 +/- 1.08 mm (P <
      0.0001). In the group treated with BG, the mean PD was reduced from 8.07 +/- 1.32
      mm to 3.85 +/- 0.66 mm and the mean CAL changed from 9.78 +/- 1.71 mm to 6.71 +/-
      1.89 mm (P < 0.0001). No statistically significant differences in any of the
      investigated parameters were observed between the test and control group.
      CONCLUSIONS: Within the limits of the present study, it can be concluded that
      both therapies led to significant improvements of the investigated clinical
      parameters, and the combination of enamel matrix derivative and bioactive glass
      does not seem to additionally improve the clinical outcome of the therapy.

PMID- 11990442
TI  - Comparison of clinical, radiographic, and histometric measurements following
      treatment with guided tissue regeneration or enamel matrix proteins in human
      periodontal defects.
AB  - BACKGROUND: The purpose of this study was to compare the clinical and
      radiographic parameters with the histometric findings following 2 different
      regenerative procedures in humans. METHODS: Fourteen advanced intrabony defects
      at teeth scheduled for extraction were randomly treated as follows: 8 with guided
      tissue regeneration (GTR) using bioabsorbable barriers and 6 with an enamel
      matrix protein derivative (EMD). Standardized radiographs, probing depths (PD),
      and attachment levels (CAL) at baseline and 6 months after therapy were evaluated
      and compared to the histometric measurements made following the removal of teeth
      and surrounding tissues 6 months after the surgery. RESULTS: Significant PD
      reductions (GTR: -5.62 mm; EMD: -5.00 mm) and CAL gains (GTR: 3.87 mm; EMD: 2.67
      mm) were observed in both groups. Six months after surgery, minor resorptions of
      the alveolar crest (AC) (GTR: 0.40 mm; EMD: 0.33 mm) and bony gain at the bottom
      of the defects (GTR: 0.47 mm; EMD: 1.05 mm) were observed radiographically. No
      statistically significant differences in the change of clinical and radiographic
      parameters between the GTR and EMD groups were found. Histometrically,
      significant amounts of new connective tissue attachment (i.e., cementum with
      inserting collagen fibers) were observed in both groups (GTR: 2.29 mm; EMD: 1.81
      mm). Bone regeneration was found to be significant only in the GTR group (GTR:
      1.93 mm; EMD: 0.78 mm). However, the study lacked statistical power for
      determining equivalence between the groups. CONCLUSIONS: Within the limitations
      of the present study, it may be concluded that at 6 months after GTR or enamel
      matrix protein derivative therapy, formation of new cementum and bone may be
      histometrically demonstrated. Except for the formation of new bone, no
      statistically significant differences between both therapies could be seen for
      clinical, radiographic, and histometric results 6 months after surgery.

PMID- 11990443
TI  - In vivo ultrasonic debridement forces in bicuspids: a pilot study.
AB  - BACKGROUND: Hand instruments lead to application of excessive forces, resulting
      in extensive root substance removal. Ultrasonic debridement primarily removes
      accretions from root surfaces. However, there is a lack of information on
      procedural aspects of ultrasonic debridement. The purpose of the present study
      was to assess the forces applied by different therapists during ultrasonic root
      surface debridement of bicuspids in periodontal patients in vivo. METHODS: Ten
      dentists and 10 dental hygienists each debrided 1 aspect of a bicuspid with
      moderate chronic periodontitis using an ultrasonic curet. The forces applied were
      recorded using a piezo-electric receiver built into the handle of the ultrasonic
      curet, an electronic transducer, and an analogous writer. The force recordings
      were converted from millivolts into Newtons (N). Mean positive and negative
      forces were calculated for each therapist, and t tests were used to assess
      differences in these forces between dentists and dental hygienists. RESULTS: The
      results showed that the mean positive force applied by dentists was 1.00 N (range
      0.53 to 1.34 N). The corresponding mean value for dental hygienists was 0.77 N
      (range 0.20 to 1.22 N). The mean root debridement time was 110.2 seconds (range
      38 to 165 seconds) for dentists and 90.8 seconds (range 38 to 244 seconds) for
      dental hygienists. The mean percentage of total debridement time used for
      positive force application by dentists was 76.1%, and for dental hygienists
      63.9%. Negative forces impacting on the periodontal soft tissues were also
      recorded. These negative forces reached a mean of 0.16 N for dentists and 0.31 N
      for dental hygienists. CONCLUSIONS: From these observations, it may be concluded
      that application of ultrasonic debridement therapy is highly subjective, and that
      dentists and dental hygienists may not be adequately trained to use these
      instruments optimally.

PMID- 11990444
TI  - A clinical comparison of a bovine-derived xenograft used alone and in combination
      with enamel matrix derivative for the treatment of periodontal osseous defects in
      humans.
AB  - BACKGROUND: Enamel matrix protein derivative (EMD) and particulate anorganic
      cancellous bovine-derived bone xenograft (BDX) have both shown favorable clinical
      results in reducing intrabony periodontal defects as compared to open flap
      debridement alone. These materials have shown results comparable to those
      obtained with guided tissue regeneration. The primary aim of the present study
      was to evaluate the effectiveness of EMD combined with BDX as compared to BDX
      alone, with a secondary aim to compare the treatment outcomes of the 2
      modalities. METHODS: Seventeen patients with paired intrabony defects and probing
      depths measuring > or = 5 mm who were being treated for chronic periodontitis
      were selected for this controlled, blinded, split-mouth study. Following non
      surgical periodontal therapy, sites were randomly selected to receive either a
      combination of EMD and BDX (test group) or BDX alone (positive control group).
      Baseline and 6-month surgical reentry measurements were taken by a calibrated
      examiner blinded to the treatment. A paired Student t test was utilized to
      evaluate differences between baseline and post-treatment and between the
      treatment groups. RESULTS: Favorable clinical outcomes for both hard and soft
      tissue measurements were achieved for both treatment groups when compared to
      baseline (P < 0.001). There was no statistically significant difference for any
      of the measured clinical parameters. Probing depth reduction for the test group
      and control group was 4.2 +/- 1.1 mm and 3.9 +/- 1.3 mm, respectively (P > 0.8).
      Mean gain in clinical attachment levels for the test and control groups was 3.8
      +/- 0.9 mm and 3.7 +/- 1.5 mm, respectively (P > 0.6). Hard tissue measurements
      obtained at surgical reentry were used to calculate the bone fill (BF) and
      percent bone fill (%BF). The BF was 3.2 +/- 1.4 mm and 3.0 +/- 1.2 mm (P > 0.6),
      and the %BF was 63.3 +/- 16.3% and 67.0 +/- 19.0% (P > 0.4) for the EMD + BDX and
      BDX groups, respectively. CONCLUSIONS: In summary, both the particulate anorganic
      cancellous bovine-derived bone xenograft used alone and in combination with
      enamel matrix derivative are effective for the treatment of human intrabony
      periodontal lesions.

PMID- 11990445
TI  - Clinical comparison of an enamel matrix derivative used alone or in combination
      with a bovine-derived xenograft for the treatment of periodontal osseous defects
      in humans.
AB  - BACKGROUND: The combination of bone replacement graft materials has been
      suggested for the treatment of periodontal osseous defects. The purpose of this
      study was to evaluate the effectiveness of enamel matrix derivative (EMD)
      combined with a bovine-derived xenograft (BDX) as compared to EMD alone in the
      treatment of intraosseous defects in patients with moderate to advanced
      periodontitis. METHODS: Sixteen adult patients with at least 2 intrabony defects
      were entered in this split-mouth design study. Defects were treated with EMD
      alone or EMD + BDX. Reentries were performed 6 to 8 months after initial surgery.
      The following soft and hard tissue measurements were recorded prior to initial
      surgery and at reentry: probing depth (PD), gingival margin location, clinical
      attachment level (CAL), depth of defect, and crestal bone level. Statistical
      analyses were performed to determine changes in PD, CAL, fill of osseous defect,
      and crestal resorption. Percentages of bone fill (%BF) and defect resolution
      (%DR) were also calculated. RESULTS: The most significant results were that
      gingival recession was greater for the group treated with EMD alone (0.8 +/- 0.8
      mm) compared to EMD + BDX (0.3 +/- 0.6 mm) (P = 0.04) and bone fill was greater
      for EMD + BDX (4.0 +/- 0.8 mm) compared to EMD alone (3.1 +/- 1.0 mm) (P = 0.02).
      The measures for PD reduction, attachment level gain, crestal resorption, %BF,
      and %DR did not present a statistically significant difference (P > 0.10).
      CONCLUSIONS: This study evaluated the performance of EMD + BDX and EMD alone. The
      results demonstrated that a significant improvement in clinical parameters was
      observed. When comparing both modalities, a statistically significant difference
      was only found for gingival recession and bone fill, yielding a more favorable
      outcome towards the combined approach.

PMID- 11990446
TI  - Relationship of clinical depression to periodontal treatment outcome.
AB  - BACKGROUND: Depression has been associated with periodontal disease; however, its
      relationship to periodontal treatment outcome (PTO) has not been investigated.
      METHODS: Data were obtained by chart abstraction and computer databases on 1,299
      health maintenance organization (HMO) patients aged 30 to 64 who had concurrent
      medical, dental, and pharmacy benefits, and who had an initial periodontal
      examination during 1996, 1997, or 1998. Depression (yes/no) was the main
      independent variable and was determined by presence of any diagnosis code for
      depression on the patient record. PTO was determined by the difference in percent
      of sites with probing depth (PD) > or = 5 mm between the initial and 1-year post
      treatment periodontal exams. Sub-median periodontal treatment outcome (SMPTO) was
      defined as a reduction in fewer than the median percent of sites (7.33%) with PD
      > or = 5 mm. Information on sociodemographics, periodontal therapy, calculus and
      plaque, number of remaining teeth, smoking, antidepressant medications, and
      diabetes were collected. RESULTS: A total of 697 patients had a periodontal exam
      at both baseline and follow-up. Of these, 12.2% had depression. In a
      multivariable logistic model, depression (odds ratio [OR] 2.16, 95% confidence
      interval [Cl] 1.12 to 4.16) and 4-month recall treatment (OR 2.34, Cl 1.46 to
      3.75) were associated with SMPTO, while percent of sites at baseline with PD > or
      = 5 mm (OR 0.93, Cl 0.91 to 0.94), number of remaining teeth at baseline (OR
      0.94, Cl 0.89 to 0.99), and number of teeth lost during the study period (OR
      0.75, Cl 0.58 to 0.96) were negatively associated. Periodontal surgery, age,
      gender, smoking, plaque, calculus, diabetes, and antidepressant medication were
      not significant in the model. CONCLUSION: Clinical depression may have a negative
      effect on periodontal treatment outcome in this group model HMO population.

PMID- 11990447
TI  - Long-term results of guided tissue regeneration therapy with non-resorbable and
      bioabsorbable barriers. II. A case series of infrabony defects.
AB  - BACKGROUND: The aim of this 5-year follow-up case series was to clinically and
      radiographically evaluate the long-term results after guided tissue regeneration
      (GTR) therapy of infrabony defects using non-resorbable and bioabsorbable
      barriers. METHODS: In 12 patients with advanced chronic periodontitis 12 pairs of
      contralateral infrabony defects were treated. Within each patient one defect
      received a non-resorbable (expanded polytetrafluoroethylene [ePTFE]; control: C)
      and the other a bioabsorbable (polyglactin 910; test: T) barrier by random
      assignment. At baseline and at 6 and 60 +/- 3 months after surgery clinical
      parameters and standardized radiographs were obtained. Gain of bone density
      within infrabony defects was assessed using subtraction radiography. RESULTS:
      Eight of 12 patients were available for the 60-month reexaminations. Six and 60
      +/- 3 months after GTR therapy statistically significant (P < 0.05) vertical
      attachment (CAL-V) gain was observed in both groups (C6:2.6 +/- 1.4 mm; C60: 1.6
      +/- 1.5 mm; T6:3.0+/- 1.7 mm; T60: 3.0 +/- 0.7mm). However at 60 months, 2
      infrabony defects in the control group had lost all the attachment that had been
      gained 6 months after therapy and a clinically relevant but statistically in
      significant mean CAL-V loss of 1.0 +/- 2.1 mm was observed from 6 to 60 months.
      The case series failed to show statistically significant differences between test
      and control regarding CAL-V gain 60 months after surgery. Also subtraction
      analysis failed to reveal statistically significant differences regarding density
      gain between both groups 6 and 60 months postsurgically (C6: 26.4 +/- 54.2; C60
      62.8 +/- 112.7; T6: 68.7 +/- 72.8; T60. 84.1 +/- 83.6). CONCLUSIONS: CAL-V gain
      achieved after GTR therapy in infrabony defects using both non-resorbable and
      bioabsorbable barriers was quite stable after 5 years in 14 of 16 defects.

PMID- 11990448
TI  - Modulation of the host response in periodontal therapy.
AB  - This paper was prepared by the Research, Science, and Therapy Committee of the
      American Academy of Periodontology to provide the dental profession an overview
      of current and potential methods to modulate the host response in the treatment
      of periodontal diseases. Specifically, it discusses components of periodontal
      disease pathogenesis (i.e., immune and inflammatory responses, excessive
      production of matrix metalloproteinases and arachidonic acid metabolites, and
      regulation of bone metabolism) and their modulation.

PMID- 11990449
TI  - Synergistic versus antagonistic actions of glutamate and glutathione: the role of
      excitotoxicity and oxidative stress in neuronal disease.
AB  - The etiology of various age-related neurological diseases remains unknown.
      Sporadic forms ofAlzheimer's, Parkinson's and Lou Gehrig's disease have been
      linked to environmental factors that cause neuronal cell death either by
      excitotoxicity or by inducing oxidative stress. Our recent studies have
      demonstrated that various compounds not previously associated with these
      diseases, i.e. methionine sulfoximine (MSO), originally isolated from 'agenized'
      flour, and sitosterol glucoside (BSSG), isolated from the seed of the cycad,
      appear to be neurotoxins, likely acting by excitotoxic mechanisms. For these
      compounds, the primary excitotoxic effect appears to involve glutamate release
      followed by NMDA receptor activation. Lactate dehydrogenase assays demonstrate
      that both compounds cause rapid cell death in vitro. In addition, both compounds
      appear to alter antioxidant defense mechanisms, acting particularly on levels of
      reduced glutathione (GSH). In vivo application of MSO has historically been
      linked to behavioral abnormalities, including seizures, in various species. Our
      recent experiments have demonstrated that mice fed cycad flour containing
      sitosterol glucoside have severe behavioral abnormalities of motor and cognitive
      function, as well as significant levels of neurodegeneration in cortex,
      hippocampus, spinal cord and other CNS regions measured post mortem. The combined
      weight of excitotoxic action, in concert to a decline in antioxidant defenses,
      induced by molecules such as methionine sulfoximine and sitosterol glucoside is
      hypothesized to be causal to neuronal degeneration in various neurological
      diseases. Understanding the mechanisms of action of these and functionally
      related molecules may serve to focus attention on potential neurotoxins present
      in the human environment. Only once such molecules have been identified, can we
      begin to design appropriate pharmaceutical strategies to prevent or halt the
      progression of the age-related neurological diseases.

PMID- 11990450
TI  - Extracellular proteases and neuronal cell death.
AB  - Neuronal cell death occurs during development of the central nervous system as
      well as in pathological situations such as acute injury and progressive
      degenerative diseases. For instance, granule cells in the developing cerebellum
      and neuronal precursor cells in the cortex undergo programmed cell death, or
      apoptosis. There is currently strong debate conceming the mechanism of death in
      many degenerative events such as ischemia, blunt head trauma, excitotoxicity and
      neurodegenerative diseases, i.e. Alzheimer's disease. Neurons can die a necrotic
      death when the initial insult is too great; apoptosis requires "planning." For
      example, the cell death seen in the core of an ischemic infarct is necrotic,
      while in the surrounding penumbra region the death is probably apoptotic.
      Regardless of the degenerative pathway, damaged or dead neurons are a hallmark of
      many diseases including Alzheimer's, Parkinson's, glaucoma, ischemia and multiple
      sclerosis. Molecules such as cytokines, chemokines, reactive nitrogen/oxygen
      species, and proteases play an important role in promoting and/or mediating
      neurodegeneration. Proteases have been implicated in both physiological and
      pathological events, suggesting their intervention in key points when things go
      awry. In this review we will summarize recent findings linking extracellular
      proteases with neuronal cell death in both human diseases and their animal
      models.

PMID- 11990451
TI  - Molecular cloning and characterization of the mouse reticulon 3 cDNA.
AB  - cDNA of mouse reticulon 3 (mRTN3) was cloned. The cloned cDNA is 1745 bp long and
      contains an open reading frame of 237 amino acids for a 30 kDa protein. The gene
      was mapped at band B of chromosome 19 by FISH. Two altematively spliced
      transcripts, 3.4 and 2.3 kb, of mRTN3 were found by Northem blot analysis. Both
      transcripts were expressed in many tissues and embryos and the highest expression
      of the 3.4 kb-transcript was observed in the brain, especially in neurons. The
      expression of 30 kDa-mRTN3 protein was also greatest in the brain. Both N and C
      termini of mRTN3 faced the cytosol, indicating that they may recruit other
      proteins to the endoplasmic reticulum.

PMID- 11990452
TI  - Disorders of post-squalene cholesterol biosynthesis leading to human
      dysmorphogenesis.
AB  - Insights in molecular developmental biology in animals and humans are
      facilitating the understanding of pathophysiologic mechanisms in dysmorphogenesis
      or abnormalities in normal embryologic structural development. A milestone was
      recognition of the role of shh in morphogenesis of craniofacial structures,
      especially the development of holoprosencephaly. The dependence of hedgehog
      morphogens on cholesterol modification for normal hedgehog signaling function has
      particular relevance to disorders of cholesterol synthesis which manifest
      dysmorphogenesis. Four human disorders of morphogenesis (Smith-Lemli-Opitz
      syndrome, desmosterolosis, X-linked chondrodysplasia punctata, CHILD syndrome)
      have recently been shown to be caused by sterol abnormalities resulting from
      cholesterol biosynthesis enzyme deficiencies. This review summarizes the
      clinical, biochemical and molecular data in these disorders with an emphasis on
      understanding the pathophysiology of dysmorphogenesis.

PMID- 11990453
TI  - Cyclic AMP-mediated increase in L-type calcium current (ICa,L) by nitroglycerin
      in guinea-pig ventricular myocytes.
AB  - The effects of nitroglycerin (NG) on the L-type Ca2+ current (ICa,L) were
      investigated in guinea-pig ventricular myocytes. NG did not affect the basal
      ICa,L significantly. The ICa,L was increased by NG when the ICa,L was augmented
      by the pre-treatment with isoproterenol (Iso), and this increase was abolished by
      the pretreatment with methylene blue (MB), a guanylate cyclase inhibitor. NG also
      increased ICa,L in the myocytes undergoing the pretreatment with
      isobutylmethylxanthine (IBMX). The NG-induced increase in ICa,L was also observed
      in the myocytes intracellularly dialyzed with cyclic adenosine monophosphate
      (cAMP). The order of the Iso-induced increase in ICa,L was Iso, IBMX and cAMP.
      Relatively a lower concentration of the extracellularly applied 8bromo-cyclic
      guanosine monophosphate (8Br-cGMP) increased ICa,L in the myocytes dialyzed with
      cAMP, whereas the higher concentration of 8Br-cGMP decreased ICa,L. NG produced a
      marked increase in cGMP levels, and a slight increase in cAMP levels in the
      ventricular tissues. These results suggest that the stimulatory effect of NG on
      the ICa,L is due to an inhibition of cGMP-inhibitable cAMP-phosphodiesterase
      (PDE) and a possible activation of cGMP-dependent protein kinase via the NG
      induced increase in cGMP levels in guinea-pig ventricular myocytes.

PMID- 11990454
TI  - Minifascicular neuropathy: a new concept of the human disease caused by desert
      hedgehog gene mutation.
AB  - We recently found a patient with 46,XY partial gonadal dysgenesis who presented
      with polyneuropathy. Sural nerve pathology revealed peculiar findings
      characterized by extensive minifascicular formation and with a decreased density
      of myelinated fibers. We found in the patient, a homozygous missense mutation at
      the initiating codon in exon 1 of the desert hedgehog (DHH) gene, which predicts
      a failure of translation of the gene. These data demonstrate that DHH is a key
      molecule in both male gonadal differentiation and perineurial formation in
      peripheral nerves.

PMID- 11990455
TI  - Hyperthermia assists survival of astrocytes from oxidative-mediated necrotic cell
      death.
AB  - In response to many stresses and pathologic states, including different models of
      nervous system injury, cells synthesize a variety of proteins, most notably the
      inducible 72 kDa heat shock protein 70 (Hsp70), which plays important roles in
      maintaining cellular integrity and viability. We report here that cultured
      astrocytes from rat diencephalon express high levels of Hsp70 upon exposure to
      elevated temperatures, and are less vulnerable to a subsequent oxidative stress.
      Complex oxidative stress was induced by exposure of astrocytes to an aqueous
      extract of tobacco smoke. This resulted in both glutathione and ATP depletion,
      along with cell death that proceeded through a necrotic pathway. Pretreatment of
      cultures with the glutathione replenishing agent, N-acetyl-L-cysteine, prevented
      glutathione and ATP loss as well as necrotic cell death. Thermal stress also
      protected astrocytes from necrotic cell death but without affecting glutathione
      or ATP levels. We propose that heat shock protects astrocytes from necrosis
      induced by oxidative stress, probably as a result of Hsp70 synthesis, through an
      antioxidant-ATP independent mechanism. As Hsp70 may transfer from glial to
      neuronal cells, its synthesis by astrocytes may represent an important survival
      mechanism by which astrocytes protect neurons against oxidative-mediated cell
      death.

PMID- 11990456
TI  - Association of a gliotoxic activity with active multiple sclerosis in US
      patients.
AB  - We recently found that cerebrospinal fluid (CSF) from multiple sclerosis (MS)
      patients contains a gliotoxic activity which induces programmed cell death of
      astrocytes and oligodendrocytes and could be the main contributing factor to the
      massive glial cell death seen in MS active lesions. A previous clinical study
      aimed at evaluating the gliotoxicity of CSF from a cohort of MS patients from
      France indicated that MS patients with the active form of the disease do indeed
      present significant CSF gliotoxicity. To extend this observation, the effect of
      141 CSFs from United States patients with different neurological diseases
      (including 71 MS) was tested on immortalized astrocytes. A cell death assay
      showed that a gliotoxic activity is significantly present in the CSF from MS
      patients with the active forms. Thus, this gliotoxic activity may represent a
      critical pathogenic factor in the neuropathology of active MS by playing a role
      both in demyelinisation and alteration of the blood-brain barrier.

PMID- 11990457
TI  - Induction of cell death in rat brain by a gliotoxic factor from cerebrospinal
      fluid in multiple sclerosis.
AB  - The cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients contains a 17
      kDa glycoproteic factor with gliotoxic properties in vitro. In order to study the
      physiopathological role of this gliotoxic factor in vivo, we have injected a
      partially purified preparation and appropriate controls in rat CSF and
      investigated whether it induces cell death in the rat central nervous system
      (CNS), 10 days and 3 months after injection. We used the TUNEL assay in
      association with specific immunohistochemistry to characterize dying cells in the
      gliotoxic factor- treated rat CNS. At 10 days post-injection, TUNEL-positive
      cells were observed in the whole rat CNS. They were particularly numerous in the
      choroid plexus, ependymal epithelium, cerebral white matter, cerebral vascular
      endothelium, arachnoid spaces and less frequent in the gray matter of brain and
      spinal cord. The predominant type of TUNEL-positive cells observed at 10 days
      post-injection was astrocytes, in white matter, gray matter, occasionnally around
      damaged endothelial cells in periventricular and subpial spaces. Other TUNEL
      positive cells were identified as oligodendrocytes by an oligodendrocyte specific
      RIP immunostaining, at 10 days post-treatment with the gliotoxic factor.
      Interestingly, demyelination and death of oligodendrocytes were more important 3
      months post-injection: TUNEL-RIP positive oligodendrocytes were generally
      associated with multifocal demyelinating areas. Clearly, the 17 kDa gliotoxic
      factor injection in rat CSF triggers demyelination and may be used as a new
      animal model for MS. Also, our results suggest a new possible scenario for MS
      pathogenesis: death of oligodendrocytes and astrocytes, stimulated by the MS
      gliotoxic factor causes the breakdown of the blood-brain barrier (BBB) and the
      demyelinating cascade.

PMID- 11990458
TI  - The HERV-W/7q family in the human genome. Potential for protein expression and
      gene regulation.
AB  - A new family of human endogenous retroviruses has recently been discovered. The
      best known example of a full length member of this family, HERV-W/7q, is located
      on chromosome 7. HERV-W/7q is characterized by a long open reading frame within
      its env gene which is expressed in various tissues, and mainly in placenta, as a
      protein that we called enverin. A search for new retroviral sequences related to
      the HERV-W/7q family allowed the characterization of such elements in chromosome
      6. A novel full length HERV with an env gene of the HERV-W/7q type, potentially
      encoding a truncated form of enverin has been identified on chromosome 10. The
      distribution of HERV-W/7q related sequences close to or within genes offers the
      possibility that the expression of these genes may be regulated by their
      companion retroviral sequences.

PMID- 11990459
TI  - The expression and significance of intracellular T helper cytokines in systemic
      lupus erythematosus.
AB  - To analyze the Th1 and Th2 paradigm of peripheral T helper cells in patients with
      systemic lupus erythematosus (SLE). The intracellular Th1 and Th2 cytokines were
      analyzed in fresh blood T cells from 20 SLE patients who had not yet received any
      treatment. Th1 and Th2 cells were quantitated based on their intracellular
      cytokine content as assessed by flow cytometry. Cytokine expressions were
      correlated with clinical features, laboratory findings, and disease activities.
      There was no difference in the expression of intracellular IFN-y, or IL-4 between
      SLE patients and healthy controls. However, the IL-2 and IL-10 levels were
      significantly higher and lower respectively in the lupus patients than in the
      control group. In addition, patients with arthritis had higher IFN-gamma
      expression than patients without arthritis. Moreover, patients with serositis or
      CNS involvement had higher IL-4 expression than in patients without these
      manifestations. There was no correlation between the SLEDAI scores and the
      cytokine expression levels. However, patients with serum anti-ds DNA antibodies
      had higher IL-10 levels than in those without these antibodies. The present study
      demonstrates that a Th1 pattern of intracellular cytokines predominates in
      patients with SLE prior to treatment. The pattern of particular intracellular T
      cell cytokines may suggest specific clinical manifestations and disease
      progression of SLE.

PMID- 11990460
TI  - Repeated treatment with S. aureus superantigens expands the survival rate of
      Ehrlich ascites tumor bearing mice.
AB  - The bacterial superantigen Staphylococcal enterotoxin-A (SEA), produced by some
      strains of Staphylococcus aureus, causes proliferation of cytotoxic T-lymphocytes
      and cytokine production in vivo. SEA has been shown to be highly efficient for
      antibody-targeted superantegen immunotherapy for different tumor models. A
      candidate B-cell superantigen that has received considerable attention these days
      is staphylococcal protein-A (PA). It has been shown to possess multiple
      immunological responses. The anti-tumor property of PA is well documented in the
      literature in various transplantable tumors of rats and mice. In the present
      study, we have shown that the T-cell superantigen SEA and B-cell superantigen PA
      induce immunomodulatory and anti-tumor activity which is strongly protentiated by
      PA + SEA co-administration. Combination treatment with PA and SEA prolongs the
      immune response in vivo, limits the development of immunological unresponsiveness
      and promotes maximum anti-tumor effects to tumor carrying animals, as compared
      with PA or SEA alone. The immune response after combined therapy is characterized
      by substantially augmented IFN-gamma, TNF-alpha, Nitric oxide and strong CTL
      activity. Our data demonstrate that combined PA + SEA therapy induces long-term
      survival of the animals, carrying the Ehrlich ascites tumor.

PMID- 11990461
TI  - Differences in the sensitisation to ragweed pollen and occurrence of late summer
      allergic symptoms between native and immigrant workers of the nuclear power plant
      of Hungary.
AB  - Regular medical screening including allergic symptoms of workers of the Nuclear
      Power Plant in Paks, Hungary, offered a unique opportunity to study the influence
      of the environmental factors on the development of allergy. The city Paks has
      been one the areas of the country most heavily exposed to ragweed pollen
      allergens. The occurrence and extent of sensitisation assessed by skin prick test
      to common allergens and prevalence of seasonal and perennial allergic symptoms
      were compared among 880 workers (695 immigrants, 185 natives) with self-reported
      allergic symptoms. The percentage of sensitised people against common allergens
      (ragweed, grass, D. pteronyssinus) was almost the same in the natives and
      immigrants. When, however, the strength of sensitivity to ragweed was determined
      by quantitative skin prick test and specific IgE determination, significantly
      (P<0.0001) more immigrants (69%) than native workers (20%) exhibited high
      sensitivity to ragweed and the titres of specific IgE antibodies was also
      significantly (p < 0.0001) higher in the former group. Similar differences were
      found in the occurrence and type of allergic symptoms. Seasonal symptoms alone
      occurred in 69% and 38% of the immigrant and native workers (p < 0.0001). This
      difference was mostly due to those with late summer symptoms characteristic to
      ragweed allergy. These symptoms occurred in 57% of the immigrant workers, much
      more frequently (p < 0.0001) than in the natives (18%). Our findings indicate
      that the length of exposure to an inhalant allergen does affect the extent of
      sensitisation to ragweed allergen and markedly influences the clinical symptoms
      that develop in the ragweed allergic patients upon allergen exposure. It can be
      assumed that the natives who have been living with ragweed pollen for a long time
      (that is were exposed to natural immunotherapy), developed a natural tolerance to
      it.

PMID- 11990462
TI  - Senescent erythrocytes: factors affecting the aging of red blood cells.
AB  - Human red blood cells (RBC) have a well-defined lifespan of 120 days affected by
      many cellular parameters. The aim of the present study was to investigate through
      a functional assay the effect of some factors in the interaction of erythrocytes
      with monocytes: heat rigidification, equilibration at different pH and
      desialyzation. We also studied the interaction between stored RBC and peripheral
      blood monocytes with this functional erythrophagocytosis assay. Blood samples
      from 30 volunteer donors were investigated. 1) Senescent (Se) and Young (Y) RBC
      were obtained by differential centrifugation. 2) Erythrocyte suspensions:
      Aliquots of each sample were subjected to the following treatments: a)
      Rigidification by heat (RRBC), b) Equilibration at different pH (5.34, 6.30,
      7.33, 9.20) and c) Desialyzation with neuraminidase and trypsin. The functional
      assay was performed incubating monocytes obtained by glass adherence with these
      suspensions of RBC. Whole blood samples (n = 20) were stored during different
      periods of time (0, 7, 14, 21, 28, 35 and 42 days). The erythrophagocytosis assay
      was performed during six weeks incubating isologous monocytes with RBC from every
      unit. Negative and positive controls were performed using non sensitized (NSRBC)
      and sensitized with IgG anti-RhD (SRBC) red cells. The percentage of active
      monocytes (AM) obtained were: 1) YRBC: 2.8 +/- 0.9 and SeRBC: 17.5 +/- 2.1; 2a)
      RRBC: 3.0 +/- 0.9; 2b) 10.9 +/- 0.9, 15.5 +/- 0.8, 3.1 +/- 1.0, 4.0 +/- 1.1; 2c)
      11.1 +/- 1.4 and 3.9 +/- 1.0; SRBC 32.1 +/- 1.7 and NSRBC: 2.8 +/- 1.5. The % of
      AM with SeRBC was higher (p < 0.001) than those obtained with NSRBC. The data of
      AM with RRBC were significantly lower (p < 0.001) than those obtained with SeRBC
      and SBRC, indicatingthat heat rigidification of RBC does not increase
      phagocytosis by monocytes. The values of AM obtained from the suspensions of
      erythrocytes equilibrated at different pH indicate that the acidification of RBC
      increases the interaction with monocytes. The % AM with neuraminidase treated RBC
      was higher than those observed with YRBC and NSRBC (p < 0.001). No modifications
      were observed with trypsin treated RBC. These results suggest that the loss of
      sialic acid may be involved in the physiological phagocytosis. The values of AM
      of stored whole blood were: 2.3 +/- 1.3, 2.7 +/- 1.3, 4.4 +/- 1.6, 6.7 +/- 1.2,
      9.6 +/- 1.0, 11.7 +/- 0.8 and 13.0 +/- 1.2. The results showed a significant
      increase in the % of AM as a function of the preservation time from 2,3 +/- 1,3
      for the first day to 13,0 +/- 1,2 for the 42nd day (p < 0.001). The data obtained
      in this ex vivo model show a significant increase (p<0.001) in the phagocytosis
      of RBC equilibrated at low pH, desialinized (greater than 80%) with neuraminidase
      and stored for over 28 days. These factors would be involved in erythrocyte
      removal via phagocytosis during tissular homeostasis.

PMID- 11990463
TI  - Immunogene therapy of tumors with a vaccine based on the ligand-binding domain of
      chicken homologous integrin beta3.
AB  - The breaking of immune tolerance against angiogenesis-associated molecules should
      be a useful approach for cancer therapy by active immunity. We used chicken
      integrin beta3 as a model antigen to explore the feasibility of immunogene
      therapy of the tumors with a vaccine based on a single xenogeneic homologous
      gene, targeting the molecules associated with angiogenesis. To test this concept
      we constructed a plasmid DNA encoding the ligand-binding domain of chicken
      integrin beta3 (P-BD-C) and control vectors. We found that immunogene therapy of
      tumors with a vaccine based on the ligand-binding domain of chicken integrin
      beta3 (P-BD-C) was effective in both protective and therapeutic anti-tumor
      immunity in several tumor models in mice. Autoantibodies against integrin beta3
      in sera of mice immunized with the ligand-binding domain of chicken integrin
      beta3 could be found by Western blot analysis and ELISA assay. The purified
      immunoglobulins were effective in the inhibition of endothelial cell
      proliferation in vitro, and in anti-tumor activity as well as in the inhibition
      of angiogenesis by adoptive transfer in vivo. The anti-tumor activity and the
      production of integrin beta3-specific autoantibodies (manifested by significantly
      elevated Ig G1 and Ig G2b) could be abrogated by the depletion of CD4+ T
      lymphocytes. These observations may provide a vaccine strategy for cancer therapy
      through the induction of the autoimmunity against the molecules associated with
      tumor growth in a cross-reaction with a single xenogeneic homologous gene and may
      be of importance in the further exploration of the applications of other
      xenogeneic homologous genes identified in human and other animal genome sequence
      projects in cancer therapy.

PMID- 11990464
TI  - Tumor cell prothrombotic properties.
AB  - Thrombin generation and fibrin formation are constantly determined in patients
      with malignancy, who are at increased risk of thromboembolic complications. Most
      importantly, fibrin formation is also involved in the processes of tumor spread
      and metastasis. Activation of blood coagulation in cancer is a complex
      phenomenon, involving many different pathways of the hemostatic system and
      numerous interactions of the tumor cell with other blood cells, including
      platelet, monocyte and endothelial cell. Tumor cells possess the capacity to
      interact with all parts of the hemostatic system. They can directly activate the
      coagulation cascade by producing their own procoagulant factors or they can
      stimulate the prothrombotic properties of other blood cell components. All of the
      mechanisms are not entirely understood, however research studies in the last ten
      years have greatly improved our knowledge of tumor-promoted pro-thrombotic
      functions.

PMID- 11990465
TI  - Fibrinogen and tumor cell metastasis.
AB  - Detailed studies tumor cell-associated procoagulants and fibrinolytic factors
      have strongly suggested that local thrombin and plasmin generation may be
      important in tumor progression. Given that one target for both these serine
      proteases is fibrinogen, a logical extension of this hypothesis is that local
      fibrin deposition and dissolution may be key determinants of tumor growth and/or
      dissemination. To directly test this concept, we initiated studies of tumor
      growth, experimental metastasis, and spontaneous metastasis in C57Bl/6-inbred
      mice with and without fibrinogen. Using two established C57Bl/6-derived tumor
      cell lines, Lewis lung carcinoma and B16-BL6 melanoma, fibrinogen deficiency was
      found to strongly diminish, but not prevent, the development of lung metastases
      in both experimental and spontaneous metastasis assays. This difference was not a
      consequence of any obvious difference in tumor stroma formation or the growth of
      primary or secondary tumors. Rather, tumor cell fate studies argued that there is
      an important role of fibrin(ogen) in the sustained adhesion and/or survival of
      tumor cell emboli within the lung. The specific thrombin inhibitor, hirudin, was
      also shown to strongly diminish metastatic potential, consistent with earlier
      reports. More importantly, hirudin was found to further diminish the already low
      metastatic potential of tumor cells in fibrinogen-deficient mice. We conclude
      that fibrin(ogen) is a critical determinant of metastatic potential, but thrombin
      appears to contribute to tumor cell dissemination through at least one fibrinogen
      independent mechanism. Further, these findings suggest that therapeutic
      strategies directed at several hemostatic factors might be useful in the
      suppression of metastatic disease.

PMID- 11990466
TI  - Relationship of blood clotting and tumor angiogenesis.

PMID- 11990467
TI  - Targeted delivery of tissue factor to tumor neovasculature for cancer therapy.

PMID- 11990468
TI  - Thrombospondin-1: an inhibitor of angiogenesis.

PMID- 11990469
TI  - Inhibition of angiogenesis with heparin?

PMID- 11990470
TI  - The human vascular mapping project. Selection and utilization of molecules for
      tumor endothelial targeting.

PMID- 11990471
TI  - Venous thromboembolism and occult malignancy: an historical perspective.

PMID- 11990472
TI  - Screening for cancer in patients with venous thromboembolism.

PMID- 11990473
TI  - Idiopathic venous thromboembolism as a first manifestation of cancer.
AB  - Since Trousseau's time it has been documented the strong two-way relationship
      between cancer and venous thromboembolism (VTE). Moreover it has been clearly
      demonstrated that patients with a first episode of idiopathic VTE exhibit a
      higher risk of newly discovered cancer during follow-up when compared to those
      suffering from secondary VTE. The performance of a selected diagnostic work-up
      for cancer detection at the time of referral for index VTE in these patients
      appears to be capable to identify most of these malignancies and the earlier
      detection is likely to be associated with improved treatment possibilities and
      thus prognosis.

PMID- 11990474
TI  - A number needed to screen and cost-effectiveness analysis of the SOMIT-data.

PMID- 11990475
TI  - Arterial thrombotic syndromes in cancer patients.

PMID- 11990476
TI  - Autoimmune bleeding disorders in cancer patients.

PMID- 11990477
TI  - Cancer and DIC.

PMID- 11990478
TI  - The coagulopathy of acute promyelocytic leukemia.

PMID- 11990479
TI  - Molecular regulation of blood clotting in tumor biology.
AB  - TF expression is a hallmark of cancer progression. The procoagulant functions of
      TF that lead to thrombin generation are critically important to support
      metastasis, in part through the generation of fibrin that assures prolonged
      arrest of tumor cells in target organs. In addition, the coagulation initiation
      complex, i.e. TF-VIIa-Xa, generates autocrine cell signaling though protease
      activated receptors. A cooperation of the TF cytoplasmic domain with protease
      signaling may explain the diverse contributions of TF to metastasis and
      angiogenesis.

PMID- 11990480
TI  - Cancer metastasis: a model of cell-protease and cell-cell interactions.

PMID- 11990481
TI  - Tumor cell-platelet interaction in metastatic disease.

PMID- 11990482
TI  - u-PA and cell migration: urokinase receptor as a ligand for a chemotactic G
      protein-coupled receptor.

PMID- 11990483
TI  - Properties and function of heparanase in cancer metastasis and angiogenesis.
AB  - Cleavage of heparan sulfate proteoglycans affects the integrity and functional
      state of tissues and thereby fundamental normal and pathological phenomena
      involving cell migration and response to changes in the extracellular
      microenvironment. Heparanase, degrading heparan sulfate (HS) at specific
      intrachain sites, is synthesized as a latent approximately 65 kDa protein that is
      processed at the N-terminus into a highly active approximately 50 kDa form. The
      heparanase enzyme is preferentially expressed in human tumors and its
      overexpression in low-metastatic tumor cells confers a highly invasive phenotype
      in experimental animals. Heparanase also releases angiogenic factors and
      accessory fragments of HS from the tumor microenvironment and induces an
      angiogenic response in vivo. These effects were best demonstrated when the enzyme
      was secreted and/or expressed on the cell surface. Heparanase may thus facilitate
      tumor cell invasion, vascularization and survival, all critical events in cancer
      progression. These observations, the anti-cancerous effect of heparanase
      inhibiting molecules, and the unexpected identification of a single predominant
      functional heparanase suggest that the enzyme is a promising target for drug
      development.

PMID- 11990484
TI  - Platelets cross-talk with tumor cells.

PMID- 11990485
TI  - An overview of thromboprophylaxis in malignancy.

PMID- 11990486
TI  - Management of thromboembolic disease in cancer patients.

PMID- 11990487
TI  - Biochemistry of cancer procoagulant.
AB  - Cancer procoagulant (CP), EC3.4.22.26, is a cysteine proteinase produced by
      malignant or fetal tissue. It is a single chain Mr 68 kDa protein containing no
      carbohydrates. Prevalent amino acids are Ser (19.15), Gly (18.7%), Glu (12.5%),
      Lys (8.1%) and Asp (7.1%). Amino-acid sequence of CP is not determined yet. The
      natural substrates for CP are coagulation factor X and probably PAR-1 receptor.
      However, the peptidyl bond in factor X molecule hydrolyzed by CP is different
      from the bond recognized by other known FX-activators. Peptidyl chromogenic
      substrates hydrolyzed by CP are those with Pro at P2 and Arg or Lys at P1
      position. Factor X-activating activity of CP is inhibited by number of various
      inhibitors: peptidyl diazomethyl ketones. iodoacetamide, mercuric chloride, PMSF,
      leupeptin and antipain. It has been demonstrated that E-64, a specific inhibitor
      of cysteine proteinases, inhibits CP reversible acting as a competitive inhibitor
      of the enzyme. The CP activity is modulated by the presence of divalent metal
      ions in the reaction environment. Ca2+, Cd2+, Mg2+ and Mn2+ ions potentiate the
      procoagulant activity when Cu2+, Fe2+, Sn2+ and Zn2+ ions inactivate CP.

PMID- 11990488
TI  - Adhesion and inhibition assay of Mycoplasma genitalium and M. pneumoniae by
      immunofluorescence microscopy.
AB  - Adhesion of Mycoplasma pneumoniae and the closely related M. genitalium to HEp-2
      cells was investigated. The main surface proteins known to be involved in
      adhesion are P1 of M. pneumoniae and its homologue, MgPa, of M. genitalium. Both
      proteins are also immunodominant proteins. Protein P116 is another immunodominant
      protein of M. pneumoniae. These immunogenic proteins were investigated for their
      surface exposure and involvement in adhesion to host epithelial cells.
      Immunofluorescence microscopy (IFM) was used to detect M. pneumoniae and M.
      genitalium adhering to HEp-2 cells. Monospecific antibodies were produced against
      fragments of the surface proteins lacking tryptophan stop codons and were used
      for adhesion detection, surface exposure and adhesion inhibition IFM assays.
      Three monospecific antibodies were made against MgPa covering regions in the N
      terminal, the middle and the C- terminal part; two monospecific antibodies were
      produced against P1 covering regions of the N- and the C-terminal part and one
      monospecific antibody was made against most of P116. Only the C-terminal parts of
      P1 and MgPa were surface exposed and blocking of these regions with the
      monospecific antibody resulted in inhibition of cytadsorption. Protein P116 was
      shown to be surface exposed and an essential protein involved in adhesion because
      the anti-P116 antibody prevented attachment of M. pneumoniae to the HEp-2 cells
      independently of P1. This study adds to the understanding of the molecular
      biology of M. genitalium and M. pneumoniae and presents a method to study the
      proteins involved in adhesion of these mycoplasmas.

PMID- 11990489
TI  - Distribution of type III secretion gene clusters in Burkholderia pseudomallei, B.
      thailandensis and B. mallei.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, carries a cluster
      of genes closely related in organisation to the type III secretion (TTS) system
      gene clusters of the plant pathogens Ralstonia solanacearum and Xanthomonas spp.
      The TTS gene cluster (TTS1) is present only in B. pseudomallei and not in
      avirulent B. thailandensis. Adjacent to the gene cluster encoding putative
      secreton structural proteins lie a number of open reading frames (ORFs) encoding
      putative proteins with little or no homology to known proteins, with the
      exception of one predicted protein with homology to Pseudomonas syringae HrpK. In
      both R. solanacearum and Xanthomonas spp., genes in this location encode secreted
      effector proteins. RT-PCR analysis indicated that TTS genes, including two of
      these ORFs, are expressed in broth at 37 degrees C. Analysis of genome sequence
      data identified a second cluster of TTS genes (TTS2) present in both B.
      pseudomallei and B. mallei (99% identity). However, B. mallei appears to lack the
      TTS1 gene cluster. PCR assays indicated that TTS2 was also present in B.
      thailandensis. TTS1 and TTS2 are similar in gene organisation, but nucleotide
      sequences are sufficiently divergent to suggest that the two TTS systems may have
      different roles.

PMID- 11990490
TI  - Inhibition of cell proliferation and induction of apoptosis by Helicobacter
      pylori through increased phosphorylated p53, p21 and Bax expression in
      endothelial cells.
AB  - Microcirculation plays a crucial role in mucosal physiological function as well
      as repair of gastric mucosal damage. Endothelial cell damage is known to disturb
      microcirculation and suppress angiogenesis. Therefore, the direct effect of
      Helicobacter pylori on endothelial cells in vitro was investigated with H. pylori
      water extract. The effect of H. pylori water extract on cell proliferation and
      apoptosis of human umbilical vein endothelial cells (HUVECs) was evaluated. The
      ratio of BrdU-positive HUVECs in both cagA/vacA-positive and -negative H. pylori
      water extract-treated groups was significantly lower at 24 h than that in the
      control group, but Escherichia coli water extract did not affect the
      proliferation of these endothelial cells. Apoptosis was induced by H. pylori
      water extracts after incubation for 24 h in a cagA/vacA-independent manner. In
      the mitochondrial permeability transition assay, tetramethylrhodamine methyl
      ester was accumulated in mitochondria of HUVECs. Western blot analysis showed no
      difference in the level of total p53 protein in H. pylori water extract-treated
      and non-treated cells, but the level of phosphorylated p53 protein was increased
      in the treated cells at 15 and 60 min after addition of the extract. Reverse
      transcription (RT)-PCR products for p21 and Bax were elevated in the H. pylori
      water extract-treated cells. p21 levels began to increase 0.5-1 h after addition
      of the extract, whereas Bax increased in the period 0.5-2 h. H. pylori induced a
      disturbance of cell proliferation and apoptosis in the vascular endothelial cells
      which may contribute to gastric mucosal injury and to delayed healing of gastric
      lesions.

PMID- 11990491
TI  - A molecular and phenotypic study of Vibrio cholerae in Iran.
AB  - Vibrio cholerae is again the subject of attention on account of the current
      increase in the world-wide incidence of cholera. In this study, 200 clinical
      isolates of V. cholerae serotypes O1 and non-O1, non-O139, were collected from
      different provinces in Iran. The isolates were subjected to biochemical analysis,
      antibiogram, PCR of toxin genes, plasmid profile, ribotyping and pulsed-field gel
      electrophoresis (PFGE). The analysis of plasmid content showed that 33-96% of V.
      cholerae isolated from different provinces carry a large plasmid. PCR analysis of
      V. cholerae O1 showed that the genes encoding cholera toxin (ctx), toxin co
      regulated pilus (tcp), accessory cholera enterotoxin (ace) and zonula occludens
      toxin (zot) were present in 55-97% of isolates in different provinces.
      Restriction fragment length polymorphism (RFLP) of BglI-digested DNA probed with
      five oligonucleotides revealed three different ribotype patterns in isolates of
      V. cholerae O1. The ribotype pattern B21 of V. cholerae O1 El Tor was found to be
      the predominant pattern in the isolates studied. V. cholerae non-O1, non-O139
      isolates showed a single ribotype pattern. PFGE analysis also showed 10 different
      patterns amongst the isolates, 9 of which were in V. cholerae O1. Overall, the
      analysis of polymorphism of ribotypes and PFGE patterns of the isolates showed
      that the provinces in Iran were affected by a limited number of clones of V.
      cholerae O1 and non-O1, non-O139 strains.

PMID- 11990492
TI  - Subtype distribution of Haemophilus influenzae isolates from north India.
AB  - A total of 120 Haemophilus influenzae isolates from blood, cerebrospinal fluid,
      sputum and throat swabs of patients and carriers in North India was characterised
      by biotyping, ribotyping and random amplification of polymorphic DNA (RAPD)-PCR.
      Of these, 77 isolates (64%) were serotype b; the other 43 (36%) were non-typable.
      Biotype I was the most predominant among the typable strains and biotype II among
      the non-typable strains. Ribotyping with restriction endonucleases HaeIII and
      EcoRI differentiated the isolates into three and six ribotypes, respectively.
      However, RAPD fingerprints generated by the application of arbitrary primers AP1
      and AP2 provided a higher level of discrimination. RAPD typing revealed distinct
      polymorphism among the serologically typable isolates. This study is the first
      report that stratifies the subtypes of H. influenzae strains from India by
      molecular techniques.

PMID- 11990493
TI  - Clonal structure of Shiga toxin (Stx)-producing and beta-D-glucuronidase-positive
      Escherichia coli O157:H7 strains isolated from outbreaks and sporadic cases in
      Hokkaido, Japan.
AB  - A total of 22 clonal phenotypic variants of Shiga toxin (Stx)-producing
      Escherichia coli (STEC) O157:H7 was isolated from six different locations in
      Hokkaido, Japan. These isolates were negative for sorbitol fermentation but
      positive for beta-D-glucuronidase (GUD+). They carried eaeA, EHEC-hlyA, pas and
      etpD genes like typical E. coli O157:H7 and, in addition, st1 and stx2 genes.
      However, they were shown to lack katP and espP genes that are present in typical
      STEC O157:H7. All these atypical GUD+ STEC O157:H7 isolates had very similar
      antimicrobial susceptibilities. Pulsed-field gel electrophoresis analysis with
      XbaI, SfiI, SwaI, SpeI and NotI indicated that they were identical or closely
      related to one another. From their phenotypic and genotypic features, these GUD+
      STEC O157:H7 isolates may represent a distinct clone among STEC O157.

PMID- 11990494
TI  - DNA-PCR and RT-PCR for the 18-kDa gene of Mycobacterium leprae to assess the
      efficacy of multi-drug therapy for leprosy.
AB  - DNA-PCR and reverse transcription (RT)-PCR for the 18-kDa protein of
      Mycobacterium leprae were used to examine the efficacy of multi-drug therapy
      (MDT) in leprosy. MDT was administered for 0-24 months. Fourteen (63.6%) of 22
      patients showed positive PCR results after treatment for 12 months and the
      positive results decreased to 30% after 24 months of MDT. These results did not
      correlate with the bacterial index (BI) or the IgM antibody titre for the
      phenolic glycolipid (PGL)-1. One-dimensional densitometric analysis of agarose
      gels from PCR from the longitudinal study showed a gradual reduction of the 360
      bp band after 12-24 months of MDT. RT-PCR for mRNA of the 18-kDa protein
      successfully tracked bacterial RNA changes in the biopsies and confirmed a
      decrease in the RNA of M. leprae in patients after MDT for 12 months. Thus, DNA-
      and RT-PCR for the 18-kDa protein of M. leprae are effective in assessing the
      efficacy of MDT for leprosy.

PMID- 11990495
TI  - Increased release of glucuronoxylomannan antigen and induced phenotypic changes
      in Trichosporon asahii by repeated passage in mice.
AB  - Clinically important fungi such as Candida albicans and Cryptococcus neoformans
      are known to undergo phenotypic changes after repeated subculture or passages in
      vivo. However, there are no reports describing this phenomenon in Trichosporon
      species. This study investigated whether in-vivo passages of environmental
      isolates of Trichosporon asahii in mice changes their phenotype; three
      environmental isolates and 14 clinical isolates (from deep-seated infections)
      were used. The shape of the colony and cell type were observed, and the titre of
      glucuronoxylomannan (GXM) antigen and concentration of (1-->3)-beta-D-glucan were
      measured for each isolate. Changes in these features were also examined after
      three passages of the environmental isolates in mice. The shape of colonies and
      cell types were clearly different in environmental and clinical isolates.
      Furthermore, the clinical isolates released significantly higher levels of GXM
      antigen than environmental isolates (titre: log2 9.4 SD 0.7 versus log2 5.4 SD
      1.4). The phenotype of passaged isolates was significantly different from the
      original environmental isolates with respect to the morphology of colonies and
      cell type and GXM release (titre: log2 10.0 SD 0.7 versus log2 5.4 SD 1.4). These
      results suggest that the phenotypic changes in T. asahii occur as a result of in
      vivo passages. This process may allow a proportion of the fungal population to
      escape eradication by the host immune system, as GXM antigen is considered to
      protect the fungi against phagocytosis by polymorphonuclear leucocytes and
      monocytes in vivo.

PMID- 11990496
TI  - Combined detection of mannanaemia and antimannan antibodies as a strategy for the
      diagnosis of systemic infection caused by pathogenic Candida species.
AB  - A novel strategy for the diagnosis of systemic candidosis was evaluated, based on
      the combination of two enzyme immunoassays that detect a candida oligomannoside
      repetitive epitope expressed in large amounts by Candida albicans (Platelia
      Candida Ag), and antibodies against C. albicans mannan, the major cell-wall
      immunogen in which this epitope is present (Platelia Candida Ab). Sera were
      selected retrospectively from intensive care and haematology patients with
      clinically suspected systemic candidosis, and from whom Candida spp. had been
      isolated from normally sterile sites. Of the 21 patients infected with C.
      albicans, 13 had positive antigenaemia and 14 had a positive antibody response,
      including eight patients who were antigenaemia negative. The sensitivity of the
      combined tests was 100%. In patients infected with C. glabrata (n = 12) or C.
      tropicalis (n = 10), the sensitivity was 83% and 80%, respectively. For the
      remaining patients, infected with C. parapsilosis (n = 10), C. krusei (n = 8) or
      C. kefyr (n = 2), the sensitivity of the combined tests was 40%, 50% and 50%,
      respectively. At least one of the serological tests was positive before yeast
      growth occurred in 60% of patients for whom a serum sample was available before
      blood culture sampling. An increase in serological test positivity to >80% was
      observed for sera obtained around the date of positive culture, irrespective of
      the Candida species isolated. These results suggest that regular serological
      monitoring for both mannanaemia and anti-mannan antibodies in at-risk patients
      may contribute to the early diagnosis of candidosis.

PMID- 11990497
TI  - PCR detection of Streptococcus mutans and S. sobrinus in dental plaque samples
      from Japanese pre-school children.
AB  - Streptococcus mutans and S. sobrinus are associated with the development of
      dental caries. These bacteria were detected by PCR and then their presence was
      compared with the incidence of dental caries in 77 Japanese pre-school children.
      Plaque samples were collected from all erupted tooth sites in the subjects, aged
      3-5 years old and each with primary dentition, with a sterile toothbrush. A
      dental examination was performed for dmft (decayed, missing, filled, total) with
      the WHO caries diagnostic criteria. In all subjects, the prevalence of S. mutans
      and S. sobrinus was 72.8% and 61.1%, respectively; 19 (24.7%) were positive for
      S. mutans alone, 10 (13.0%) were positive for S. sobrinus alone, 37 (48.1%) were
      positive for both S. mutans and S. sobrinus, and 11 (14.3%) were negative for
      both S. mutans and S. sobrinus. The dmft scores of children positive for both S.
      mutans and S. sobrinus were significantly higher than those positive for S.
      mutans alone. These results indicate that children harbouring both S. mutans and
      S. sobrinus have a significantly higher incidence of dental caries than those
      with S. mutans alone.

PMID- 11990498
TI  - Changes in predominant bacterial populations in human faeces with age and with
      Clostridium difficile infection.
AB  - The bacterial composition of human faeces can vary greatly with factors such as
      age and disease, although relatively few studies have monitored these events,
      particularly at species level. In this investigation, bacteria were isolated from
      faecal samples from healthy young adults and elderly subjects, and elderly
      patients with Clostridium difficile-associated diarrhoea (CDAD). The organisms
      were identified to species level on the basis of their cellular fatty acid
      profiles with the MIDI system. In some groups of bacteria, species diversity was
      found to change with age despite the overall numbers of organisms being similar
      at genus level. Bacteroides thetaiotaomicron, B. ovatus and Prevotella tannerae
      were common gram-negative anaerobes isolated from young adults. Bacteroides
      species diversity increased in the faeces of healthy elderly people.
      Bifidobacterial species diversity decreased with age, with Bifidobacterium
      adolescentis and Bif. angulatum being the most common isolates. CDAD patients
      were characterised by greater diversity of facultative species, lactobacilli and
      clostridia, but greatly reduced numbers of bacteroides, prevotella and
      bifidobacteria. Such bacterial population changes in the normal microbiota could
      result in metabolic conditions favourable for the establishment of pathogenic
      micro-organisms, such as clostridia, and would have considerable effects on the
      biochemical capacity of the large intestine as a whole. Alterations in the
      community structure of bifidobacteria and lactobacilli have relevance for dietary
      and therapeutic interventions such as the use of pre- or probiotics that aim to
      modify the composition or metabolic activities of the intestinal microflora in a
      beneficial way, particularly in elderly people or individuals at risk of CDAD.

PMID- 11990499
TI  - Evaluation of desorption of proteins adsorbed to hydrophilic surfaces by two
      dimensional electrophoresis.
AB  - The evaluation of the plasma protein adsorption patterns of superparamagnetic
      iron oxide (SPIO) particles is of high interest concerning their in vivo fate and
      is carried out by two-dimensional electrophoresis (2-DE). The sample preparation
      is of great importance, especially the removal of the adsorbed proteins
      (desorption) from the particle surface for subsequent analysis by 2-DE. The
      removal is carried out by a desorption solution. In this study, negatively and
      positively charged SPIO model particles were under investigation concerning the
      desorption of proteins adsorbed on their surfaces. Firstly, the desorption
      process was determined quantitatively using the Bradford protein assay. Secondly,
      the removable or nonremovable protein species, from particles surface were under
      investigation by 2-DE. Looking at the desorption in a quantitative manner with
      the Bradford assay, the desorption efficacy from negatively charged particles was
      about 90%. In the case of the positively charged particles, the desorption
      efficacy seemed to be reduced, approximately 34% of the proteins remained on the
      surface. Comparing the protein patterns of the particles evaluated by 2-DE in the
      desorption solution and the proteins remaining on the particles, they confirmed
      the results from the protein quantification. After desorption, the IgG gamma
      chains were found to be the dominant protein fraction remaining on the negatively
      charged particles. On the positively charged particles, many more protein species
      were found after desorption. The more basic the protein fragments, the more
      ineffective was the desorption from the positively charged model particle, and
      vice versa. Nevertheless, all protein spots were found qualitatively in the
      desorption solution, especially when the desorption solutions still containing
      the particles were used for the 2-DE analysis. In conclusion, 2-DE could be
      confirmed as the "gold standard" for determining the plasma protein adsorption
      patterns of nanoparticulate systems.

PMID- 11990500
TI  - Direct visualization of serine hydrolase activities in complex proteomes using
      fluorescent active site-directed probes.
AB  - The field of biochemistry is currently faced with the enormous challenge of
      assigning functional significance to more than thirty thousand predicted protein
      products encoded by the human genome. In order to accomplish this daunting task,
      methods will be required that facilitate the global analysis of proteins in
      complex biological systems. Recently, methods have been described for
      simultaneously monitoring the activity of multiple enzymes in crude proteomes
      based on their reactivity with tagged chemical probes. These activity based
      probes (ABPs) have used either radiochemical or biotin/avidin-based detection
      methods to allow consolidated visualization of numerous enzyme activities. Here
      we report the synthesis and evaluation of fluorescent activity based probes for
      the serine hydrolase super-family of enzymes. The fluorescent methods detailed
      herein provide superior throughput, sensitivity, and quantitative accuracy when
      compared to previously described ABPs, and provide a straight-forward platform
      for high-throughput proteome analysis.

PMID- 11990501
TI  - Downsizing proteolytic digestion and analysis using dispenser-aided sample
      handling and nanovial matrix-assisted laser/desorption ionization-target arrays.
AB  - An efficient technique for enzymatic digestion of proteins in nanovial arrays and
      identification by peptide mass fingerprinting using matrix-assisted laser
      desorption/ionization (MALDI-MS) is presented in this work. Through dispensing of
      a protein solution with simultaneous evaporation the protein (substrate) is
      concentrated up to 300 times in-vial. At higher substrate concentrations the
      catalytic turnover numbers increase according to the Michaelis-Menten kinetics.
      Therefore, the dispenser-aided nanodigestion is valuable for identification of
      low-level proteins (10 nM-500 nM) as well as for automatic high efficiency
      digestions performed in 0.2-10 min. As an example of low-level protein
      identification, a 10 nM solution of lysozyme C was unambiguously identified after
      5 min of nanodigestion. Moreover, only 30 s nanodigestion was sufficient to
      identify hemoglobin (10 microM), exemplifying the fast catalysis of the
      nanodigestion technique. The developed silicon flow-through piezoelectric
      dispenser is adapted for low-volume and preconcentrated samples in the nL-microL
      range and provides fast, accurate and contact-free sample positioning into the
      nanovials. In this work, the properties of the nanodigestion concept regarding
      proteins of different characteristics are explored. Furthermore, the potential of
      automated protein identification using precoated proteolytic nanovial-arrays is
      demonstrated.

PMID- 11990502
TI  - Application of chemical selective cleavage methods to analyze post-translational
      modification in proteins.
AB  - Three chemical specific cleavage reactions, one for the carboxyl side of aspartyl
      peptide bonds, one for the carboxyl side of asparaginyl peptide bonds and another
      for the amino side of seryl/threonyl peptide bonds have been recently
      established. Additionally, these reactions simultaneously react on several post
      translationally modified groups in peptides or proteins. The modified groups
      cover the external modifications N-formyl, N-acetyl, N-pyroglutamyi residues and
      C-terminal-alpha amide, as well as the internal modifications such as O-acetyl
      serine, phosphorylated serine/tyrosine, sulfonylated tyrosine, glycosylated
      serine/threonine and glycosylated asparagine. These three cleavage reactions
      relate to key amino acids for modifications, deamidation for asparagine,
      phosphorylation and acetylation for serine, and glycosylation for asparagine,
      serine and threonine. The chemical reactions on these modifications change the
      peptide mapping pattern, and information from these reactions may contribute
      characterization and location of post-translational modified groups in the
      protein.

PMID- 11990504
TI  - The mitochondrial antioxidant defence system and its response to oxidative
      stress.
AB  - The antioxidant systems of mitochondria are not well known. Using a proteomics
      based approach, we defined these mitochondrial antioxidant systems and analyzed
      their response to oxidative stress. It appears that the major mitochondrial
      antioxidant system is made of manganese superoxide dismutase on the one hand, and
      of peroxiredoxin III, mitochondrial thioredoxin and mitochondrial thioredoxin
      reductase on the other hand. With the exception of thioredoxin reductase, all
      these proteins are induced by oxidative stress. In addition, a change in the
      peroxiredoxin III pattern can also be observed.

PMID- 11990503
TI  - Regulation of growth factor induced gene expression by calcium signalling:
      integrated mRNA and protein expression analysis.
AB  - There is considerable indirect evidence that growth factor induced changes in the
      intracellular concentration of calcium play an important role in the regulation
      of the mammalian cell cycle. However, the precise mechanism by which this may be
      achieved remains unclear. Here we show that SKF-96365, an inhibitor of growth
      factor induced capacitative calcium entry (CCE), inhibits cell cycle progression
      by preventing entry into S phase. SKF-96365 changes the temporal profile of
      growth factor induced calcium signalling and recent studies have shown that
      alterations in the temporal and spatial patterns of calcium signalling can
      differentially regulate gene expression. We have therefore sought to examine the
      effect of inhibition of CCE on growth factor induced gene expression during G1.
      To achieve this we have initiated a combined transcriptomic and proteomic
      approach to measure CCE regulated gene expression using cDNA arrays and two
      dimensional polyacrylamide gel electrophoresis, respectively. The initial results
      of this on-going analysis are reported here. They reveal that inhibition of CCE
      influences the expression of 29 genes at the mRNA level and 22 genes at the
      protein level. We report the identification of the mRNAs whose expression is
      altered by inhibition of CCE and describe the potential functional significance
      of some of these changes. The value of integrating a transcriptomic and two
      dimensional gel electrophoresis based proteomic approach to studies of gene
      expression is discussed.

PMID- 11990505
TI  - Differentially expressed proteins in the interaction of Xanthomonas axonopodis
      pv. citri with leaf extract of the host plant.
AB  - The present study reports the expression of proteins of Xanthomonas axonopodis
      pv. citri in response to different growth conditions. The bacterium was cultured
      in the basal medium MM1 and in the presence of leaf extracts from a susceptible
      host plant (sweet orange) as well as a resistant (ponkan) and a nonhost plant
      (passion fruit). The protein profiles were analyzed by two-dimensional gel
      electrophoresis (2-DE). Twelve differential spots (induced, up- and down
      regulated and repressed) were observed in the protein profiles of the bacterium
      cultivated in citrus extract (susceptible host) when compared to that of MM1. The
      2-DE profile of the bacterium cultured in the complex medium nutrient yeast
      glycerol was also obtained and the comparison with that of MM1 revealed 36
      differential spots. Five proteins from the different treatments were successfully
      N-terminally sequenced and the putative functions were assigned by homology
      searches in databases. Two constitutively expressed proteins, B4 and B5, were
      identified as pseudouridine synthase and elongation factor P, respectively. The
      large subunit of ribulose 1,5-biphosphate carboxylase/oxygenase and a sulfate
      binding protein were found as specifically up-regulated in the presence of citrus
      extracts. Finally, the heat shock protein G was found exclusively in the complex
      medium and repressed in all other media.

PMID- 11990506
TI  - Proteomic analysis of a developmentally regulated secretory vesicle.
AB  - Secretion of spore coat proteins from the prespore secretory vesicles (PSVs) in
      Dictyostelium discoideum is a signal mediated event that underlies terminal cell
      differentiation, and represents an important case of developmentally regulated
      secretion. In order to study the biochemical mechanisms that govern the regulated
      fusion of the PSVs with the plasma membrane and the subsequent secretion of their
      cargo, we purified this organelle from prespore cells. Analysis of protein
      extracts of highly purified PSVs indicated that, in addition to the cargo of
      structural spore coat proteins, many more proteins are associated with the PSVs.
      Their identification is paramount to the understanding of the mechanism of
      regulated secretion in this system. In this study we have taken the first
      comprehensive proteomic approach to the analysis of an entire, previously
      uncharacterized, organelle, with the goal of identifying the major proteins
      associated with the PSVs. We show that in addition to the structural spore coat
      proteins, the PSVs contain the enzymes needed for proper spore coat assembly
      (thioredoxin 2 and 3), regulatory proteins which we predict receive and transduce
      the developmental signal for secretion (rab7 GTPase, PI-3 kinase, NDP kinase and
      the calcium binding proteins calfumirin-1 and calreticulin) as well as proteins
      that interact with the cytoskeleton to mediate movement of the PSVs to the plasma
      membrane (actin binding proteins coactosin and profilin 1). In addition, the
      results suggest that proteins can play multiple roles in the cell, and that
      protein function can be dictated in part by subcellular localization. The
      identification of the PSV proteins is allowing us to develop testable hypotheses
      about the roles of these proteins within the functional context of
      developmentally regulated secretion.

PMID- 11990507
TI  - Proteomic analysis of Fasciola hepatica excretory-secretory products.
AB  - This paper describes a global investigation of the components of Fasciola
      hepatica excretory-secretory (ES) products by a proteomic approach. Despite the
      absence of a F. hepatica genome sequencing project we have shown that it was
      possible to identify 29 of the 60 prominent proteins found using two-dimensional
      gel electrophoresis. As well as cathepsin L proteases, a number of enzymes
      implicated in parasite protection from the host immune system were also found to
      be present in relatively large abundance. These included superoxide dismutase,
      thioredoxin peroxidase, glutathione S-transferases and fatty acid binding
      proteins, all of which may play a part in the detoxification of reactive oxygen
      intermediates. Interestingly, ovine superoxide dismutase was the only protein
      from the host identified on the gel. We suggest that the relative abundance and
      protective nature of the components of the ES products of this organism play an
      important role in its survival within the host. The precise identification, to
      individual NCBI database entries, of a number of glutathione S-transferases and
      cathepsin Ls from F. hepatica, by peptide mass fingerprinting, was hampered by
      multi-database submissions of the two protein superfamilies from this organism.

PMID- 11990508
TI  - Similarity of the Escherichia coli proteome upon completion of different
      biopharmaceutical fermentation processes.
AB  - A comprehensive view of the physiological state of Escherichia coli cells at the
      completion of fermentation processes for biopharmaceutical production was
      attained via two-dimensional gel electrophoretic analysis of cellular proteins.
      For high cell density fermentations in which phosphate is depleted to induce
      recombinant protein expression from the alkaline phosphatase promoter, proteome
      analysis confirms that phosphate limitation occurs. Known phosphate starvation
      inducible proteins are observed at high levels; these include the periplasmic
      phosphate binding protein and the periplasmic phosphonate binding protein. The
      phn (EcoK) locus of these E. coli K-12 strains remains cryptic, as demonstrated
      by failure to grow with phosphonate as the sole phosphorus source. Proteome
      analysis also provided evidence that cells utilize alternative carbon and energy
      sources during these fermentation processes. To address regulatory issues in the
      biopharmaceutical industry, comparative electrophoretic analyses were conducted
      on a qualitative basis for four different fermentation processes. Using this
      approach, the protein profiles for these processes were found to be highly
      similar, with the vast majority (85-90%) of proteins detected in all profiles.
      The observed similarity in proteomes suggests that multiproduct host cell protein
      immunoassays are a feasible means of quantifying host-derived polypeptides from a
      variety of biopharmaceutical fermentation processes.

PMID- 11990509
TI  - Characterisation of rice anther proteins expressed at the young microspore stage.
AB  - In combination with two-dimensional polyacrylamide gel electrophoresis (2-DE)
      protein mapping and mass spectrometry analysis, the pattern of gene expression in
      specific tissues at a specific stage can be displayed and characterised. We used
      this approach for rice (Oryza sativa L. cultivar Doongara) to display and assign
      identity to proteins in the anthers at the young microspore stage. Over 4000
      anther proteins in the pI range of 4-11 and molecular mass range of 6-122 kDa
      were reproducibly resolved after silver staining, representing about 10% of the
      estimated total genomic output of rice. Two hundred and seventy-three protein
      spots have been extracted either from polyninylidene diffluoride membrane blots
      or from colloidal Coomassie blue stained 2-DE gels and analysed by N-terminal
      sequencing, Matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MS) analysis or tandem MS sequencing. This enabled identification
      of 53 anther protein spots representing 43 different proteins. Using the publicly
      available rice expressed sequence tag (EST) database at the National Centre for
      Biotechnology Information, a further 37 protein spots were matched to ESTs. After
      BLAST searching with these ESTs, we were able to predict the identity of 22 of
      these protein spots. Proteome reference maps of rice anthers have been
      constructed according to the SWISS-2DPAGE standards and are available for public
      access at http://semele.anu.edu.au/2d/2d.html.

PMID- 11990510
TI  - A proteomics approach towards understanding blast fungus infection of rice grown
      under different levels of nitrogen fertilization.
AB  - Proteins extracted from leaf blades of rice plants infected with blast fungus,
      Magnaporthe grisea, were separated by two-dimensional polyacrylamide gel
      electrophoresis. The separated proteins were electroblotted onto a polyvinylidene
      difluoride membrane, and 63 proteins were analyzed by a gas-phase protein
      sequencer. The N-terminal amino acid sequences of 33 out of 63 proteins were
      determined in this manner. N-terminal regions of the remaining proteins could not
      be sequenced. The internal amino acid sequences of 12 proteins were determined by
      sequence analysis of peptides obtained by the Cleveland peptide mapping method.
      The amino acid sequences were compared with those of known plant and animal
      protein sequences to understand the nature of these proteins. As expected, leaf
      blades revealed predominantly the presence of photosynthetic proteins. Using this
      experimental approach named as proteome analysis, the functional proteins during
      blast fungus infection of rice with different levels of nitrogen nutrient were
      analyzed. Twelve proteins which appeared to change with different levels of
      nitrogen nutrient were identified. It was revealed that the level of ribulose-1,5
      bisphosphate carboxylase/oxygenase was increased by top-dressing with nitrogen
      nutrient. Additionally, the pathogenesis related protein were observed following
      blast fungus infection using immunoblot analysis. It was conjectured that these
      proteins might be involved in incompatible interaction in rice plants following
      blast fungus infection. The information obtained on the amino acid sequences and
      antibodies interaction is expected to be helpful in predicting the function of
      these proteins.

PMID- 11990511
TI  - Limited acid hydrolysis as a means of fragmenting proteins isolated upon
      ProteinChip array surfaces.
AB  - ProteinChip array technology enables protein purification, protein profiling, and
      biomarker discovery on a convenient biochip platform. Traditional proteomic
      approaches towards protein identification rely upon the generation of peptides
      through the use of specific proteases. However, for a variety of reasons, the
      digestion of proteins bound to planar arrays by specific proteases, such as
      trypsin, has proven to be difficult, at times providing little or no protein
      digestion at all. Additionally, should more than one protein be present on the
      array surface, the digestion product consists of peptides from different
      proteins, adding another dimension of complexity to database mining approaches.
      These factors have driven our group to explore alternative means of on-chip
      protein digestion. In this article, we describe an approach to generate peptide
      maps by limited acid hydrolysis. Depending upon the adsorbed protein, this method
      requires between 500 femtomole to 5 picomole of protein for on-chip hydrolysis.
      Besides generating several internal peptide fragments, limited acid hydrolysis
      also has the advantage of generating peptide ladders from the N- or C-terminus of
      the protein. From these ladders, partial primary sequence of the protein can be
      directly derived when analyzed by a simple laser desorption/ionization mass
      spectrometer. Furthermore, tandem mass spectrometry can be performed on several
      internal peptide fragments, thus facilitating the identification of several
      proteins within a mixture. Based upon the preliminary results of this work, we
      continue to explore the possibility of using limited acid hydrolysis to identify
      unknown proteins captured on ProteinChip array surfaces.

PMID- 11990512
TI  - Risk of childhood leukaemia in the vicinity of nuclear installations--findings
      and recent controversies.
AB  - The identification of a local excess of cancer cases, possibly associated with
      ionizing radiation, always receives substantial media coverage and communication
      about clusters is difficult. We reviewed studies that examined the risk of
      leukaemia among young people near nuclear installations. An excess of leukaemia
      exists near some nuclear installations, at least for the reprocessing plants at
      Sellafield and Dounreay and the nuclear power plant Krummel. Nonetheless, the
      results of multi-site studies invalidate the hypothesis of an increased risk of
      leukaemia related to nuclear discharge. Up until now, analytic studies have not
      found an explanation for the leukaemia clusters observed near certain nuclear
      installations. The hypothesis of an infectious aetiology associated with
      population mixing has been proposed, but needs to be investigated further. The
      review illustrates two recent examples in France (La Hague reprocessing plant)
      and in Germany (Krummel power plant), where controversies developed after reports
      of increased leukaemia risks. These examples show the importance of recalling the
      current epidemiological knowledge and of using systematic recording of cases to
      replace the alleged excesses in a more general framework. Some elements should
      also be suggested from the recent French and German experiences to reinforce
      credibility in the results.

PMID- 11990513
TI  - Thyroid cancer after X-ray treatment of benign disorders of the cervical spine in
      adults.
AB  - While there is very good epidemiological evidence for induction of thyroid cancer
      by radiation exposure in children, the risk for adults after exposure is still
      uncertain, especially when concerning relatively small radiation doses. A cohort
      of 27,415 persons which in 1950 through 1964 had received x-ray treatment for
      various benign disorders in the locomotor system (such as painful arthrosis and
      spondylosis) was selected from three hospitals in Northern Sweden. A proportion
      of this cohort, consisting of 8 ,44 persons (4,075 men and 4,069 women), had
      received treatment to the cervical spine and thereby received an estimated
      average dose in the thyroid gland of about 1 Gy. Standard incidence rates (SIR)
      were calculated by using the Swedish Cancer Register. In the cervical spine
      cohort, 22 thyroid cancers were found versus 13.77 expected (SIR 1.60, CI 1.00
      2.42). The corresponding figures for women were 16 observed cases versus 9.60
      expected cases (SIR 1.67: Cl 0.75-2.71). Most thyroid cancers (15 out of 22) were
      diagnosed > 15 years after the exposure. In the remaining part of the total
      cohort, i.e. those without cervical spine exposure, no increased risk of thyroid
      cancer was found (SIR 0.98, CI 0.64-1.38). The study strongly suggests that
      external radiation exposure of adults at relatively small doses increases the
      risk of thyroid cancer but also that this increase is very much lower than that
      reported after exposure in children.

PMID- 11990514
TI  - Age-adjusted chemotherapy for primary central-nervous system lymphoma--a pilot
      study.
AB  - Patients with primary central-nervous-system lymphoma (PCNSL) are treated with
      chemotherapy and cranial irradiation, which increase the risk of late
      neurotoxicity. The aim of this phase II trial was to investigate whether
      chemotherapy alone could induce durable remissions. Thirty non-immunocompromised
      patients were enrolled in two treatment groups, according to age. Patients in
      group A (< 65 years; n = 17) received carmustine, vincristine, dexamethasone,
      high-dose methotrexate and high-dose cytarabine. Patients in group B > 65 years:
      n = 13) were treated with carmustine, vincristine, dexamethasone and high-dose
      cytarabine. Both groups received intrathecal treatment. Radiotherapy was reserved
      for patients with stable or progressive disease. The overall response rate in
      group A was 65% (complete response 35%; partial response 29%) and in group B. 61%
      (complete response 23%; partial response 38%), but only 6 remissions were
      maintained without irradiation. In all, there were five treatment-related deaths.
      Responses were induced, but were mostly of short duration, and the treatment was
      associated with profound toxicity.

PMID- 11990515
TI  - Oncology in the nordic countries--the role of Acta Oncologica?

PMID- 11990516
TI  - Assessment of drug activity and proliferation ex vivo for prediction of outcome
      in aggressive non-Hodgkin's lymphomas.
AB  - The activity of cytotoxic drugs and tumour cell proliferation rate were assessed
      ex vivo using the fluorometric microculture cytotoxicity assay (FMCA) and
      stainings for Ki67 and mitosis in 40 patients with aggressive non-Hodgkin's
      lymphomas (NHL). The findings were correlated to clinical response and survival.
      Twenty-three patients had a complete remission and 10 a partial remission. A drug
      sensitivity index based on the cell survival for three major drugs in NHL
      treatment was derived empirically and proliferation was expressed as low-,
      intermediate- or high. In 5 out of 8 drugs tested, cell survival ex vivo was
      higher in clinical non-responders than that in responders. Using the median drug
      sensitivity index as a cut-off, the sensitivity and specificity for tumour
      response were 58% and 100%, respectively, and was similar for the proliferation
      index. Both indices combined increased the sensitivity to 73% at retained
      specificity. Intermediate/high proliferation was significantly associated with
      impaired survival, whereas the drug sensitivity index was not predictive of
      survival. Thus, ex vivo assessments of drug sensitivity and proliferation seem to
      provide prognostic information in aggressive NHL.

PMID- 11990517
TI  - Physical performance, toxicity, and quality of life as assessed by the physician
      and the patient.
AB  - The aim of this study was to study the relationship between physician-assessed
      quality of life parameters, i.e., toxicity and physical performance, and
      patients' self-reports of their quality of life (QoL). QoL was assessed at
      baseline and before each treatment, using the EORTC QLQ-C30. The WHO performance
      score (PS) and toxicity were assessed in physician interviews. The correlations
      between the WHO PS and the QLQ-C30 functioning scale scores varied from weak to
      moderate, depending on the scale. Strongest associations were found in physical-,
      social-, and role functioning, and in the global QoL. The QLQ-C30 nausea/vomiting
      and diarrhea scales correlated moderately to corresponding WHO scores. A multiple
      linear regression analysis was used to analyze the contribution of WHO PS and
      toxicity variables to the global QoL. The best model explained only 16% of the
      variance of the global QoL score. The present findings highlight the importance
      of independent QoL assessments focused on those aspects of QoL not captured in
      clinical interviews with the physician.

PMID- 11990518
TI  - Symptoms, symptom distress and health-related quality of life in patients with
      polycythaemia vera or essential thrombocythaemia during treatment with interferon
      alpha.
AB  - Sixteen patients with polycythaemia vera or essential thrombocythaemia were
      treated with interferon-alpha in order to normalize elevated platelets. Patients
      were followed for 6 months and the frequency and intensity of symptoms and side
      effects were recorded before and during the study period by the patients and by
      the doctor. Health-related quality of life was also assessed. The most frequently
      reported pretreatment symptoms were fatigue, headache and muscle pain. The
      intensity of fatigue initially increased during treatment and there was no relief
      of any of the three most frequent symptoms during the treatment period. Common
      interferon-related symptoms such as fever and chills were most frequently
      reported after one week. After one month of treatment, symptoms related to the
      gastrointestinal tract reached a peak. Two patients discontinued treatment during
      the study period. Another patient suffered severe depression after the study
      period when still on interferon. There was no difference between the frequency of
      symptoms recorded by the doctor and that reported by the patients.

PMID- 11990519
TI  - Effect of surgery on normal tissue toxicity in patients treated with accelerated
      radiotherapy.
AB  - The aim of this study was to assess the effect of surgery on normal tissue
      toxicity in head and neck cancer patients treated with accelerated radiotherapy.
      Toxicity data from two trials of accelerated radiotherapy were compared. The
      first group was taken from a phase III trial of definitive radiotherapy and the
      second group from a phase II trial of postoperative radiotherapy. The general
      eligibility criteria (apart from surgery), data collection and radiotherapy
      details for both trials were similar. The definitive group included 172 eligible
      patients and the postoperative group 52 eligible patients. At 3 weeks into
      treatment, by which time the dose and rate of dose accumulation were identical,
      there was no difference in acute toxicity. Analysis of late toxicity showed
      greater subcutaneous fibrosis in the postoperative group.

PMID- 11990520
TI  - Radiation oncology--linking technology and biology in the treatment of cancer.
AB  - Technical advances in radiation oncology including CT-simulation, 3D- conformal
      and intensity-modulated radiation therapy (IMRT) delivery techniques, and
      brachytherapy have allowed greater treatment precision and dose escalation. The
      ability to intensify treatment requires the identification of the critical
      targets within the treatment field, recognizing the unique biology of tumor,
      stroma and normal tissue. Precision is technology based while accuracy is
      biologically based. Therefore, the intensity of IMRT will undoubtedly mean an
      increase in both irradiation dose and the use of biological agents, the latter
      considered in the broadest sense. Radiation oncology has the potential and the
      opportunity to provide major contributions to the linkage between molecular and
      functional imaging, molecular profiling and novel therapeutics for the emerging
      molecular targets for cancer treatment. This process of 'credentialing' of
      molecular targets will require multi disciplinary imaging teams, clinicians and
      basic scientists. Future advances will depend on the appropriate integration of
      biology into the training of residents, continuing post graduate education,
      participation in innovative clinical research and commitment to the support of
      basic research as an essential component of the practice of radiation oncology.

PMID- 11990521
TI  - Results of external irradiation and low-dose-rate intraluminal brachytherapy for
      esophageal cancer.
AB  - The results of definitive radiotherapy to elucidate the optimal doses of external
      irradiation (ERT) and low-dose-rate intraluminal brachytherapy (ILBT) were
      analyzed. Between 1979 and 1998, 100 patients with esophageal cancer were treated
      with ERT and ILBT. ERT was given at a dose of 40-65 Gy/25-32 fractions and ILBT
      at 10-24.3 Gy/2-3 fractions. The 5-year actuarial survival rate for all cases was
      13% and that for patients with tumors of 5 cm or less in length was 22.64%, while
      for patients with tumors longer than 5 cm the rate was 5% (p < 0.005). In
      patients with tumors of 5 cm or less in length, the local control rate of those
      whose ILBT dose was 20 Gy or more was 83%, and for those with an ILBT dose of
      less than 20 Gy the control rate was 26.5% (p = 0.014). In patients with tumors
      of 5 cm or less in length, the results of treatment with 60 Gy ERT and 20 Gy ILBT
      were promising and did not cause severe late complications.

PMID- 11990522
TI  - Cancer of the larynx--treatment results after primary radiotherapy with salvage
      surgery in a series of 1005 patients.
AB  - The aim of this study is to present and discuss the results of initial
      radiotherapy with salvage surgery and to compare them with those from centres
      where primary surgery is the prevailing principle. The series comprised 1005
      consecutive patients treated during the period 1965-1998. Salvage surgery was
      performed if patients had residual tumour or developed recurrence. Disease
      specific survival (DSS) and crude survival (CS) after 5 years, among 643 patients
      with glottic carcinomas treated with curative radiotherapy was 88.6% (SE = 1.3)
      and 65.3% (SE = 2.0), respectively. Among T1 glottic carcinomas the locoregional
      control was 88%, i.e. 88% of patients were cured after radiotherapy alone, and
      the DSS was 99% both evaluated after 5 years, i.e. the salvage surgery added
      approximately 11% to the survival of T1 glottic patients. Only 4% (12/312) of T1
      glottic patients had laryngectomies. Locoregional control among T2 glottic cases
      was 67% and the DSS 88%, but, 18% (41/233) of patients lost their larynx. The
      corresponding results among T3 glottic cases were 30% and 59%, i.e. the organ
      preservation was close to 50%. Among patients with supraglottic carcinomas, the
      two estimates were 440 and 63%, respectively. Compared with our results, recent
      results published in the literature after initial laser surgery of T1 glottic
      carcinomas indicate that there are only minor differences in DSS and organ
      preservation, but it is generally agreed, but not proven, that voice quality
      after radiotherapy is better. T2 glottic carcinomas treated by initial
      supracricoid partial laryngectomy in a selected series have yielded very high DSS
      rates with better organ preservation than was observed in the present series. As
      to T3 glottic carcinomas, initial surgery does not produce better survival rates
      than those produced in the present series but our organ preservation is higher.
      The treatment of patients with supraglottic carcinoma has benefited from
      optimization of radiotherapy during recent decades. The role of initial laser
      surgery is as yet undecided.

PMID- 11990523
TI  - Serum lactate dehydrogenase isoenzyme 1 in patients with seminoma stage I
      followed with surveillance.
AB  - Serum lactate dehydrogenase isoenzyme I catalytic concentration (S-LD-1) was
      measured in patients with testicular seminoma clinical stage I followed with
      surveillance after orchiectomy. The serum samples were obtained before
      orchiectomy in 110 patients (group A) and soon after orchiectomy in 55 patients
      (group B). In group A, 60 patients (55%) had elevated S-LD-1 and 10 patients (9%)
      had elevated serum human chorionic gonadotropin concentrations (S-hCG). In group
      B, median S-LD-1 was lower than that of group A and decreased with increasing
      time after orchiectomv (p = 0.001, Jonckheere-Terpstra test, one-sided). After a
      median follow-up of 5.1 years, 23 patients (21%) in group A had relapses. The
      patients with elevated S-LD-1 and those with normal S-LD-1 had a similar relapse
      free survival (p = 0.79, log-rank test). Thus patients with seminoma stage I had
      elevated S-LD-1 more often than elevated S-hCG but an elevation in S-LD-1 did not
      predict a relapse during follow-up with surveillance. Further studies are
      required to elucidate the value of S-LD-1 in monitoring the surveillance of
      patients with seminoma stage I.

PMID- 11990524
TI  - Basic fibroblast growth factor infusion increases tumour vascularity, blood flow
      and chemotherapy uptake.
AB  - Tumour response depends on intratumoural cytotoxic concentration, which varies
      with tumour vascularity. We determined whether basic fibroblast growth factor
      (bFGF) infusion increased tumour vascularity, blood flow and cytotoxic drug
      uptake. The effect of interstitial and systemic bFGF infusion was compared with
      that of saline-infused controls using animal HSN and K12/TR tumour models.
      Changes in tumour vascularity were assessed by immunohistochemical staining of
      tumour sections. Blood flow and drug uptake were studied using a radiotracer
      method. There were significant increases in tumour vascularity, vessel length
      density and blood flow with both interstitial and systemic bFGF infusions, and a
      significant increase in tumour fluorouracil uptake after systemic bFGF infusion
      of liver tumours. The effects were independent of tumour type, and could be
      produced by bFGF administration after initial tumour growth. bFGF infusion
      increased tumour fluorouracil uptake. Further studies are required to determine
      the risks and benefits with this approach to increasing tumour cytotoxic uptake.

PMID- 11990525
TI  - Preclinical evaluations of therapies combining the vascular targeting agent
      combretastatin A-4 disodium phosphate and conventional anticancer therapies in
      the treatment of Kaposi's sarcoma.
AB  - The antitumor efficacy of the vascular targeting agent combretastatin A-4
      disodium phosphate (CA4DP) was evaluated in a xenograft model of Kaposi's sarcoma
      (KS) grown in athymic mice. Response to CA4DP alone or in combination with
      localized radiation treatment or systemic chemotherapy (cisplatin or vinblastine)
      was assessed using a clonogenic cell survival or tumor growth delay assay.
      Administering increasing doses of CA4DP to tumor-bearing mice resulted in a dose
      dependent increase in tumor cell kill. CA4DP also enhanced the antitumor effects
      of radiation and chemotherapy approximately 10-100-fold. Although single doses of
      CA4DP as large as 300 mg/kg failed to alter tumor growth, the same total dose,
      administered as 3 fractions in 5 or 9 days, resulted in significant growth delay.
      Such repeated CA4DP exposures also significantly increased the response of KS
      xenografts to cisplatin. These findings suggest that CA4DP ought to be considered
      as a candidate agent for therapeutic evaluation in AIDS-KS patients.

PMID- 11990527
TI  - Use of human CD3 monoclonal antibody for accurate CD4+ and CD8+ lymphocyte
      determinations in macaques: phenotypic characterization of the CD3- CD8+ cell
      subset.
AB  - Macaque monkeys are frequently used in models for studies of infectious diseases,
      immunity, transplantation and vaccine development. Such use is largely due to the
      conservation of functionally important cell surface molecules and the
      phylogenetic proximity of their immune systems to that of humans. Some monoclonal
      antibodies (mAb) raised against human leukocyte antigens can be utilized in the
      monkey. Until recently, many primate centers have utilized the CD2 monoclonal
      antibody to enumerate T lymphocytes. We have evaluated the anti-human CD3 mAb in
      macaques and sooty mangabeys. Using this monoclonal antibody, pigtailed macaques
      were found to have a much higher proportion of CD2+ CD3- CD8+ cells as compared
      with rhesus macaques and sooty mangabeys. Such cells comprised approximately one
      half of all CD8+ cells in the pigtailed macaque, but only one-quarter of CD8+
      cells in the rhesus, and one-fifth in the sooty mangabey. Use of the CD2
      monoclonal antibody as the T-cell marker resulted in underestimating CD4/CD8
      ratios compared with using the CD3 mAb in pigtailed macaques. Phenotypic
      characterization of this subset of CD3- CD8+ cells indicated that they are CD16+,
      CD45RA+, CD11b+, CD69+ and CD28-. This would indicate that these cells represent
      an activated natural killer cell subset.

PMID- 11990526
TI  - Activity of the vascular targeting agent combretastatin A-4 disodium phosphate in
      a xenograft model of AIDS-associated Kaposi's sarcoma.
AB  - Combretastatin A4 disodium phosphate (CA4DP) was evaluated in a xenograft model
      of AIDS-KS. KS xenografts were highly vascular, showing brisk mitotic activity,
      focal areas of necrosis, and intervening fibrovascular septae. Neoplastic cells
      were large or spindle-shaped, with vesicular nuclei and modest pleomorphism.
      Multiple junctions, microvillous-like projections, abortive lumina and rare
      Weibel Palade bodies were revealed by electron microscopy. Treatment with CA4DP
      (100 mg/kg) resulted in rapid onset of vascular effects that within 4 h resulted
      in an almost complete vascular shutdown in these tumors. Histological evaluation
      showed morphological damage within a few hours after treatment, followed by
      extensive necrosis which increased to approximately 90% by 24 h. At this time,
      viable tumor cells were evident only at the periphery of the tumor. These
      findings demonstrate not only the marked susceptibility of the KS model to CA4DP
      but also its potential application in studies related to the pathogenesis and
      therapy of AIDS-KS.

PMID- 11990528
TI  - Molecular cloning of three nonhuman primate follicle stimulating hormone beta
      subunit cDNAs.
AB  - The follicle stimulating hormone (FSH) beta-subunit cDNAs were cloned and
      sequenced for an old world primate, the rhesus monkey (Macaca mulatta), and two
      New World primates, the common marmoset (Callithrix jacchus) and pygmy marmoset
      (Cebuella pygmaea). The cDNA and predicted amino acid sequences of the rhesus
      monkey FSH beta-subunit were related most closely to the human FSH beta-subunit
      (> 96% identity). The common and pygmy marmosets have identical FSH beta-subunit
      cDNAs, whereas the marmoset FSH beta-subunit diverges from the rhesus and human
      molecules with less than 93% identity. These results have significance for the
      implementation of assisted reproductive technologies in the nonhuman primate as
      well as the evolution of genes encoding reproductive hormones.

PMID- 11990530
TI  - Haematology and blood chemistry of Cebus apella in relation to sex and age.
AB  - An effective health care program entails the prevention, diagnosis and treatment
      of medical problems. A knowledge of baseline values in clinically normal
      individuals is essential for determining the limits between good health and
      disease and for understanding the changes produced by pathogenic agents. However,
      very little information is currently available concerning the blood chemistry and
      haematological values of different species of monkeys, particularly new-world
      primates. The values of some haematological and chemical parameters in Cebus
      apella were determined. The aim of the present work was to verify the effect of
      age and sex on normal blood values. Blood samples were collected once a year for
      two successive years from 36 monkeys living in large captive social groups.
      Significant differences between males and females were found for AST, GGT, urea
      nitrogen and creatinine, erythrocytes, haemoglobin and haematocrit. Significant
      differences between juveniles and adults were found for calcium, AST, alkaline
      phosphatase, inorganic phosphorus, glucose, neutrophils, lymphocytes and serum
      protein parameters.

PMID- 11990529
TI  - Recombinant human gonadotropins for macaque superovulation: repeated stimulations
      and post-treatment pregnancies.
AB  - This report summarizes data from the superovulation and ultrasound-guided
      follicular aspiration of 40 female rhesus monkeys (Macaca mulatta) with
      recombinant human gonadotropins. Of the animals treated, 12 were stimulated for
      only one cycle, either because of a poor response to the hormones or due to
      ectopic ovarian position precluding ease of access via ultrasound. The majority
      of animals were stimulated for a minimum of 3 cycles and 3 females continued to
      respond for a minimum of 8 and a maximum of 10 cycles. For those animals with
      repeated stimulation cycles, the number of follicles developed during each of the
      stimulation protocols remained relatively comparable. Of the animals mated since
      cessation of treatment, 70% conceived. There was no difference between the
      conception rate in this subset of animals and the rest of the macaque breeding
      colony. These data indicate that participation in these studies does not impact
      on the reproductive potential of female rhesus monkeys.

PMID- 11990531
TI  - Effects of chair restraint on the strength of the tibia in rhesus monkeys.
AB  - To determine the effects of the relative inactivity and unloading on the strength
      of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure
      bending stiffness, or EI (Nm2), a mechanical property. The technique was
      validated by comparisons of in vivo measurements with standard measures of EI in
      the same bones post-mortem (r2 = 0.95, P < 0.0001). Inter-test precision was
      4.28+/-1.4%. Normative data in 24 monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg,
      revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/
      1.6 Nm2, P < 0.05). Five monkeys, restrained in chairs for 14 days, showed
      decreases in EI. There were no changes in EI in two chaired monkeys that lost
      weight during a 2-week space flight. The factors that account for both the
      decreases in bone mechanical properties after chair restraint at 1 g and lack of
      change after microgravity remain to be identified. Metabolic factors associated
      with body weight changes are suggested by our results.

PMID- 11990532
TI  - Three spontaneous lymphomas in a colony of cotton-top tamarins (Saguinus
      oedipus).
AB  - Cotton-top tamarins are well known for their prevalence to idiopathic colitis and
      adenocarcinomas. At the same time, information on the incidence of spontaneous
      lymphomas in this highly endangered species is rare. Records, 212 in total, of
      cotton-top tamarins (Saguinus oedipus) necropsied at the German Primate Centre
      between 1979 and 1998 were viewed to establish the prevalence of lymphoid
      neoplasms. Neoplastic lymphoid cell growth was mentioned in three necropsy
      records. Immunohistology was performed in all three cases on the remaining
      formalin-fixed, paraffin-embedded tissue using antibodies against CD20, CD3,
      lysozyme, Ki-67, IgM, IgG, kappa, lambda and EBNA-2. Combining histological and
      immunohistological results, the lymphomas could be differentiated into two low
      grade T-cell lymphomas and one high-grade multicentric polymorphic B-cell
      lymphoma. This corresponds to a 1.4% incidence of lymphomas in our cotton-top
      tamarin population over a period of 19 years. Although frozen material was not
      available and virological testing could not be carried out, clinical or
      histological evidence did not support an aetiological role of Herpes (H.)
      saimiri, H. ateles, simian T-cell leukaemia virus type 1 (STLV-1) or Epstein-Barr
      related herpesvirus in any of these cases. The lymphomas were considered to be
      spontaneous.

PMID- 11990533
TI  - Resonance Rayleigh-scattering method for the determination of proteins with some
      monoazo dyes of chromotropic acid.
AB  - In a weak acid medium, protein reacts with a monoazo dye of chromotropic acid,
      such as Chromazol KS (CALKS), Acid Chrome Dark Blue (ACDB), Chrome Blue SE
      (CBSE), Acid Chrome Blue K (ACBK), Chlorophosphonazo I (CPAI), Arsennazo I (AAI)
      and Chromotrope 2R (CT2R), to form a combination product. This results in a
      significant enhancement of the resonance Rayleigh-scattering (RRS) intensity, and
      the corresponding RRS spectrum appears. The characteristics of the RRS spectra of
      the combination products and the optimum conditions for the reactions were
      investigated. The intensity of RRS is directly proportional to the concentration
      of protein in a certain range. The RRS methods have high sensitivity for the
      determination of protein, the detection limits for bovine serum albumin (BSA) are
      10.0 - 30.2 ng/ml, and the sensitivity order is CALKS > AAI = CPAI > ACBK = CT2R
      > ACDB > CBSE. The selectivity for CALKS has been examined, and the method was
      applied to the determination of a microg amount of protein in a synthetic sample
      with satisfactory results.

PMID- 11990535
TI  - Simultaneous quantification of promazine hydrochloride and its sulfoxide in
      pharmaceutical preparations.
AB  - The use of derivative UV-spectrophotometry is proposed for the simultaneous
      quantification of promazine hydrochloride in the presence of sulfoxide, and vice
      versa. For this purpose, mathematical parameters were established for generating
      derivative spectra of analytes. The determination of promazine was made using the
      first-order derivative (deltalambda = 10 nm, second polynomial degree) at 268 nm.
      The quantification of sulfoxide was achieved by applying third-derivative spectra
      (deltalambda = 14 nm, sixth polynomial degree) based on measurements of the
      amplitude at 342 - 344 nm. An elaborated method was successfully used to
      determine analytes in commercial promazine pharmaceuticals. The obtained results
      agreed well with those obtained by the HPLC method.

PMID- 11990534
TI  - Resonance Rayleigh method for the determination of proteins with Orange G.
AB  - In pH 0.6 - 2.0 HCl-sodium acetate buffer solution, proteins react with an acidic
      monoazo dye such as Orange G, Methyl Orange, Methyl Red and Orange IV to form a
      combination product. This results in a significant enhancement of resonance
      Rayleigh scattering (RRS) and a new RRS spectrum appears. Owing to the fact that
      Orange G-protein system is the most sensitive, it was taken as an example to
      study. The RRS spectral characteristics of its combination product and the
      optimum condition for the reaction were investigated. The intensity of RRS is
      directly proportional to the concentration of protein in the range of 0 - 5.0
      microg/mL. The method has high sensitivity; its detection limits are 2.6 ng/mL
      for BSA, 3.4 ng/mL for HAS and 7.1 ng/mL for alpha-chymotrypsin, respectively. A
      new method for the determination of trace amounts of proteins on the basis of RRS
      spectra has been developed.

PMID- 11990537
TI  - Electrochemical characteristics of thin nickel hexacyanoferrate films formed on
      gold and thiol self-assembled monolayers modified gold electrodes.
AB  - Nickel hexacyanoferrate (NiHCF) film was prepared and characterized on gold and
      thiol self-assembled monolayers (SAMs)-modified gold electrodes. It was found
      that the film exhibited some different electrochemical characteristics compared
      with that found on a carbon electrode. In the presence of K+, the film exhibited
      a redox peak at about 0.5 V. The peak potential shifted linearly with the K+
      concentration over the range of about 0.1 mM - 0.1 M with slopes of 54 - 60 mV
      per log[K+]. However, in solutions containing Na+, Li+ or NH4+ ion the film did
      not generate well-defined peaks, or even a visible redox peak. Therefore, the
      film showed a selective potential response to K+. The voltammetric behavior of
      NiHCF film varied with thiols, the preparation procedure and the solution pH.
      Under certain conditions, the characteristics of the film could be improved to
      some extent.

PMID- 11990538
TI  - An electrochemical quartz crystal impedance study on the rising of an aqueous
      solution meniscus for a partially immersed gold electrode during the
      electrochemical reduction of oxygen.
AB  - An electrochemical quartz crystal impedance system (EQCIS) was used to study the
      resonance behavior of an AT-cut 9-MHz piezoelectric quartz crystal (PQC) with its
      Au electrode partially immersed in KCl, Na2SO4 and NaClO4 aqueous solutions,
      respectively. An in situ determination of the immersed area and the height of the
      electrode was achieved by simultaneous measurements of the PQC electroacoustic
      admittance and the electrochemical impedance. The rising of the solution meniscus
      for a gold electrode partially immersed in aqueous solutions was found at oxygen
      reduction potentials and evaluated versus the electrolyte, electrolyte
      concentration, solution pH and oxygen concentration. The solution meniscus rising
      was explained based on a lowering of the contact-angle hysteresis and a continued
      collection of the water product at the solid-gas-solution interface during oxygen
      reduction.

PMID- 11990536
TI  - Kinetic flow-injection determination of hydrogen peroxide by use of iron(III)
      catalyzed coloration and its application to the determination of biological
      substances.
AB  - A kinetic flow-injection (FI) method is described for the determination of
      hydrogen peroxide. This method is based on an iron(III)-catalyzed oxidative
      coupling of 4-aminoantipyrine with N,N-dimethylaniline by hydrogen peroxide. By
      measuring the change in the absorbance of the dye formed at 560 nm, 1 x 10(-6) -
      6 x 10(-4) M hydrogen peroxide could be determined with a sampling rate of 15 h(
      1). The relative standard deviation (n = 30) was 0.8% for 5 x 10(-5) M hydrogen
      peroxide. There was little interference of the co-existing ions and compounds.
      After introducing some immobilized enzyme reactors to the FI system, the proposed
      method allowed the determination of glucose and uric acid ranging from 1 x 10(-6)
      to 6 x 10(-4) M with relative standard deviations of below 2%. The applicability
      of the method was demonstrated by determining these substances in serum samples.

PMID- 11990539
TI  - Incorporation of horseradish peroxidase in a Kieselguhr membrane and the
      application to a mediator-free hydrogen peroxide sensor.
AB  - Horseradish peroxidase was incorporated in a kieselguhr membrane. The electron
      transfer process of the enzyme was examined by cyclic voltammetry. It was
      observed that the electron-transfer reactivity of horseradish peroxidase was
      greatly enhanced, and that direct electrochemistry was accordingly feasible.
      Using the merits of the direct electron-transfer reactivity of horseradish
      peroxidase and its specific enzymatic catalysis towards hydrogen peroxide, an
      unmediated hydrogen peroxide biosensor was constructed. The calibration plot of
      this hydrogen peroxide sensor was linear in the range of 2.0 x 10(-6) mol/L - 6.5
      x 10(-4) mol/L. The relative standard deviation was 4.1% for 6 successive
      determinations at a concentration of 1.0 x 10(-4) mol/L. The detection limit was
      1.0 x 10(-6) mol/L.

PMID- 11990540
TI  - Coulometric titration of D(+)-glucose using its enzymatic oxidation.
AB  - A definitive method is described for the indirect assay of milligram quantities
      of D(+)-glucose by coulometric titration. D(+)-Glucose was aerobically oxidized
      by glucose oxidase in an acetate buffer solution (pH 5.1). Subsequently, the
      enzymatically formed hydrogen peroxide was titrated coulometrically with
      electrogenerated hypobromite in sodium bromide-sodium tetraborate medium of pH
      8.6, with biamperometric end-point detection. Parameters affecting the
      enzymatically catalyzed oxidation and coulometric titration were evaluated. The
      optimized conditions for the oxidation of up to 20 mg of D(+)-glucose include the
      addition of 4500 U of glucose oxidase and stirring over a 10-min interval at 25
      degrees C. Under proposed conditions, the assay values of several commercial D(+)
      glucose reagents were somewhat lower than the guaranteed minimum values, with
      RSDs (n = 5) of 0.071 - 0.106%.

PMID- 11990541
TI  - Characterization of the oxidized beta-Si3N4 whisker surface layer using XPS and
      TOF-SIMS.
AB  - The change in composition of the surface layer of beta-Si3N4 whiskers was
      examined after heat treatment in atmosphere. At 873 K, the beta-Si3N4 whisker was
      barely oxidized. At 1273 K, the oxidation of the surface layers of the whisker
      occurred easily. With the beta-Si3N4 oxidation, the Si-N bond gradually changed
      into the Si-N-O bond, and finally became the oxidized layer (amorphous layer) of
      the whisker surface. It was assumed that the whisker surface has a gradient
      interface structure which gradually changes from the oxide layer of the whisker's
      outer surface to the nitride crystal of the inside layer. It was confirmed that
      impurity elements such as Y and Ca existed mainly in the amorphous region near
      the interface between the amorphous layer and the crystal layer.

PMID- 11990543
TI  - Solvent effect on ion-pair extraction of 2-(2-pyridylazo)-1-naphthol-4-sulfonate
      anion with solvated hydroxonium ion using alcohols and 1-octanol/octane mixed
      solvents.
AB  - Extraction of 2-(2-pyridylazo)-1-naphthol-4-sulfonate anion with solvated
      hydroxonium ion was carried out using 14 kinds of alcohols and 1-octanol/octane
      mixed solvents as a solvent at 25 degrees C. Alcohols are 1-pentanol, 1-hexanol,
      1-heptanol, 2-heptanol, 3-heptanol, 4-heptanol, 1-octanol, 2-octanol, 3-octanol,
      1-nonanol, 2-nonanol, 3-nonanol, 5-nonanol and 1-decanol. Among them, 1-octanol
      was found to be extremely high in extractability for 2-(2-pyridylazo)-1-naphthol
      4-sulfonate anion with hydroxonium cation. The extraction equilibrium for the
      systems using 1-octanol/octane mixed solvents was analyzed in detail in order to
      examine the extraction mechanism for these extraction systems. 2-(2-Pyridylazo)-1
      naphthol-4-sulfonate anion was found to be extracted with the hydroxonium ion
      solvated by three 1-octanol molecules as an ion-pair. The extraction and
      partition constants of the ion-pair of 2-(2-pyridylazo)-1-naphthol-4-sulfonate
      anion with solvated hydroxonium ion were estimated in the 1-octanol/octane mixed
      solvent systems.

PMID- 11990542
TI  - Extraction of lead(II) and copper(II) from salicylate media by tributylphosphine
      oxide.
AB  - Tributylphosphine oxide (TBPO) is proposed as an extractant for the extraction of
      lead(II) and copper(II) from salicylate media. The optimum conditions were
      evaluated by varying the experimental parameters, such as the pH, sodium
      salicylate concentration, tributylphosphine oxide (TBPO) concentration, shaking
      period and various diluents. The probable extracted species, deduced from log-log
      plots were Pb(HSal)2.2TBPO and Cu(HSal)2.2TBPO. The extraction took place through
      a solvation mechanism. The method permits the binary separation of lead(II) and
      copper(II) from commonly associated elements as well as the mutual separation of
      lead(II) and copper(II). The method is applicable to the determination of
      lead(II) and copper(II) in various alloys as well as environmental and
      pharmaceutical samples.

PMID- 11990544
TI  - Extraction of bismuth(III) with 2-bromoalkanoic acid in nondonating solvent from
      highly acidic aqueous solution.
AB  - The extraction behaviors of bismuth(III) with carboxylic acid (HL), which have
      not yet been clearly elucidated, because of the precipitation of hydroxide, were
      studied using the 2-bromoalkanoic acid in benzene and in hexane systems under
      aqueous conditions of high acidity at I = 1.0 M ((H,Li)NO3). The extraction
      equilibria were analyzed based on the-initial concentration of nitric acid and
      the concentration of bismuth(III) extracted in the organic phase. The extracted
      species and the logarithmic values of the extraction constant (log Kex) were
      found to be a single species of BiL3(HL)3 for the systems of 2-bromooctanoic
      acid/benzene (log Kex = -1.66) and 2-bromohexadecanoic acid/benzene (-1.58), and
      to be two species of BiL3(HL)4 (-1.01) and Bi3L9HL (-1.62) for the system of 2
      bromooctanoic acid/hexane, where the monomer was dominant at a higher reagent
      concentration.

PMID- 11990545
TI  - Effects of trimethylsilylation of copper(II)-phthalocyanine sulfonyl-aminopropyl
      silica gels on the separation of pi-electron-rich compounds by high-performance
      liquid chromatography.
AB  - As an attempt to elucidate the factor(s) responsible for the poor performance of
      a copper(II)-phthalocyanine aminopropylsilica gels (CU-PCSD) column for HPLC, the
      silanol and/or amino groups remaining on Cu-PCSD were endcapped with
      trimethylchlorosilane (TMCS) or N-trimethylsilylimidazole (TMSI). The
      trimethylsilylated Cu-PCS(D)S (Cu-PCSD-TMCS and -TMSI) were investigated
      concerning their performance as an HPLC-stationary phase in the separation of pi
      electron-rich polyaromatic hydrocarbons (PAHs), such as mutagenic anthracene and
      pyrene. As a result, trimethylsilylation with TMSI, which reacts only with
      silanol-groups, was not effective to improve the column efficiency. In contrast,
      trimethylsilylation by TMCS, which reacts with both the silanol- and amino
      groups, improved the theoretical plate numbers (N) for PAHs separation with the
      Cu-PCS(D) column, indicating that the low N values on the Cu-PCSD column were
      caused by electrostatic interactions between PAHs and the remaining amino-groups
      on Cu-PCS(D). Furthermore, the retention data of mutagenic heterocyclic amines
      (HCAs) indicated that the remaining amino groups interact with the polar groups
      of HCAs.

PMID- 11990547
TI  - Effect of the driving frequency on the emission characteristics of a radio
      frequency glow discharge excitation source boosted by the introduction of a d. c.
      bias current.
AB  - In a radio-frequency-powered glow discharge lamp, a d.c. bias current which is
      driven by a self-bias voltage can lead to an enhancement of the emission
      intensities excited by the plasma. The driving frequency of the r.f. plasma is an
      important parameter to determine the self-bias voltage; lower r.f. frequencies
      induce greater self-bias voltages. The effects of the bias current introduction
      on the emission characteristics were compared between a 13.56-MHz plasma and a
      6.78-MHz plasma. As a result, the 6.78-MHz plasma offered a better analytical
      performance, probably due to higher self-bias voltages, if the introduced Ar
      pressure was optimized. This method was applied to a Mo determination in Fe
      matrix alloy samples. At bias currents of 40 - 50 mA, the emission intensities of
      the Mo I 379.82-nm line were about 10-times larger than those obtained with the
      conventional plasma when the 6.78-MHz plasma was produced at an r.f. power of 60
      W. The detection limit obtained for this calibration was 2.0 x 10(-4) mass % Mo
      at an 80-W r.f. power and at a d.c. bias current of 68 mA.

PMID- 11990549
TI  - Individual solvation numbers around the nickel(II) ion in an N,N
      dimethylformamide and N,N-dimethylacetamide mixture determined by Raman
      spectrophotometry.
AB  - Individual solvation numbers around the nickel(II) ion have been determined by
      titration Raman spectroscopy in N,N-dimethylformamide (DMF) and N,N
      dimethylacetamide (DMA) mixtures at 298 K. The in-plane bending vibration
      (delta(O=C-N)) of DMF and the stretching vibration (v(N-CH3)) of DMA were used in
      the present analysis. These Raman bands of solvent molecules shift to higher
      frequencies upon coordination of the solvent molecules to the metal ion. By
      analyzing the band intensities of free and bound solvent molecules with
      increasing concentration of the metal ion, the solvation number around the metal
      ion can be evaluated. Because the individual solvation numbers of DMF and DMA
      around the nickel(II) ion in the mixture are determined independently, the total
      solvation number is obtained as their sum. It was found that the total solvation
      number remains 6 in all mixtures of the DMA mole fraction x = 0 - 1. Although DMF
      and DMA have practically the same electron-pair donor capacities, the nickel(II)
      ion prefers DMF to DMA, and an equal solvation number is attained at x = 0.75.
      This is ascribed to the solvation steric effect of DMA.

PMID- 11990548
TI  - Elimination of the uninformative calibration sample subset in the modified
      UVE(Uninformative Variable Elimination)-PLS (Partial Least Squares) method.
AB  - In order to increase the predictive ability of the PLS (Partial Least Squares)
      model, we have developed a new algorithm, by which uninformative samples which
      cannot contribute to the model very much are eliminated from a calibration data
      set. In the proposed algorithm, uninformative wavelength (or independent)
      variables are eliminated at the first stage by using the modified UVE
      (Uninformative Variable Elimination)-PLS method that we reported previously.
      Then, if the prediction error of the ith (1 < or =i< or = n) sample is larger
      than 3sigma, the corresponding sample is eliminated as uninformative, where n is
      the total number of calibration samples and sigma is the standard deviation
      calculated from the other n(-1) samples. Calculation of sigma by the leave-one
      out manner enhances the ability to identify the uninformative samples. The final
      PLS model is constructed precisely because both uninformative wavelength
      variables and uninformative samples are eliminated. In order to demonstrate the
      usefulness of the algorithm, we have applied it to two kinds of mid-infrared
      spectral data sets.

PMID- 11990546
TI  - Solvent strength and selectivity on a porous graphitized carbon column separated
      by a spectral mapping technique using barbiturates as solutes.
AB  - A spectral mapping technique (SPM) was employed for separating the strength and
      selectivity of the retention of 41 barbituric acid derivatives and 5 organic
      modifiers on a porous graphitized carbon column (PGC). The potency values
      calculated by SPM were considered to be indicators of the capacity of drugs to
      bind to the surface of PGC and the capacity of organic modifiers to remove the
      drugs from the surface. The dimensionality of the multidimensional selectivity
      maps was reduced to two by a nonlinear mapping technique. Calculations indicated
      that molecular lipophilicity plays a negligible role in the strength and
      selectivity of retention, proving that the retention mechanism of PGC deviates
      from those of traditional reversed-phase stationary phases. Sterical and
      electronic parameters exerted the highest influence on the retention, emphasizing
      the importance of the polar interaction and the sterical correspondence between
      the surface of PGC and the solute molecules.

PMID- 11990550
TI  - A sensitive and simple extractive-spectrophotometric method for the determination
      of microgram amount of cobalt by using alpha-benzilmonoxime.
AB  - Alpha-benzilmonoxime has been used for the extraction and determination of cobalt
      at microgram amount. The reagent reacts with cobalt(II) in the pH range of 8.8 -
      9.3 to form a yellow-color chelate, which is extracted in chloroform, toluene,
      and some other non-polar solvents. The chelate is stable in chloroform for about
      one day. Under the optimum conditions of the a-benzilmonoxime concentration and
      pH of 9.0, Beer's law was obeyed in the concentration range of 0.08 - 2.2
      microg/ml cobalt. The molar absorptivity of the extracted species was 2.55 x
      10(4) dm3/mol cm at 380 nm, with a detection limit of 0.01 microg/ml cobalt.
      Relative standard deviations of 0.4, 0.8 and 2.3% were found for the
      determination of cobalt concentrations of 2.2, 1.1 and 0.08 microg/ml,
      respectively. The effect of diverse ions on the determination of 1.00 microg/ml
      of cobalt has been studied. The method was applied to the determination of cobalt
      in vitamin B12 and B-complex ampoules, a Co2O3-Co3O4 laboratory chemical mixture
      and some synthetic alloy samples. The method is sensitive, simple, rapid and
      accurate.

PMID- 11990551
TI  - Polyvinyl alcohol as a useful indicator on iodometry: volumetric and
      spectrophotometric studies on iodine-PVA and iodine-starch complexes.
AB  - Iodometry is one of the easiest, most rapid and accurate methods for the
      determination of a relatively small amount of oxidizing agent, such as residual
      chlorine. Starch has long been used as a useful color indicator in iodometry.
      However, we found that PVA (polyvinyl alcohol with partially saponificated; e.g.,
      saponification degree of 88%) is a more useful color indicator than starch. For
      example, at 20 degrees C, the PVA indicator gave similar profiles of iodine
      concentration vs. titration efficiencies (percent recoveries) to those of starch
      at 0 degrees C. At 0 degrees C, the PVA indicator detected 1.1 mg I2/L (11 microg
      I2: with 10 mL sample volume) with a high percentage of recovery (=95%).
      Furthermore, at 20 degrees C an iodine concentration of 0.36 mg/L (which
      corresponds to a residual chlorine concentration of 0.1 mg Cl2/L) could be
      detected using PVA color indicator assuming an appropriate correction.

PMID- 11990552
TI  - Kinetic effect of zinc(II) and cadmium(II) ions on configurational inversion of
      deltaLLL-fac(S)-tris(L-cysteinato-N,S)cobalt(III) complex.
AB  - It has been confirmed from circular dichroism (CD) spectral changes of aqueous
      solutions of deltaLLL-fac(S)-[Co(L-cys-N,S)3]3- that the absolute configurational
      inversion to the ALLL isomer is remarkably accelerated by zinc(II), while it is
      retarded by cadmium(II). In the diluted solutions of these metal ions containing
      excess deltaLLL-fac(S)-[Co(L-cys-N,S)3]3-, the observed inversion rate constant
      linearly depends on the zinc(II) concentration with an intercept, while it is not
      affected by the cadmium(II) concentration. The kinetic behavior has been
      explained by difference between zinc(II)- and cadmium(II)-interactions with lone
      pairs on sulfur donor atoms of fac(S)-[Co(L-cys-N,S)3]3-. It has also been
      proposed that concentrations of zinc(II) and cadmium(II) can be simultaneously
      determined by the kinetic measurements.

PMID- 11990553
TI  - Improvement of a capillary electrophoresis-chemiluminescence detection system for
      using a polyacrylamide-coated capillary.

PMID- 11990554
TI  - Spectrophotometric determination of the partition constant for five beta
      diketones in triton X-100 micellar systems.

PMID- 11990555
TI  - Crystal structure of 4,4'-bis(4-chloro-1-phenyl-3-methyl-5-pyrazolonyl).

PMID- 11990556
TI  - Crystal structure of 1,3,5-tri(4-chlorophenyl)carbamoylurea.

PMID- 11990558
TI  - Crystal structure of 2-isopropyl-3,3,7-trimethyl-4-(m-toluidino)-1,2,3,4
      tetrahydroquinoline.

PMID- 11990557
TI  - Crystal structure of a 1beta-methylcarbapenem antibiotic, pivaloyloxymethyl
      (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[[(R)-5-oxopyrrolidin-3-yl]thio]-1
      carbapen-2-em-3-carboxylate, CS-834 dihydrate.

PMID- 11990559
TI  - Crystal structure of 2-[N-(t-butoxycarbonyl)amino]-4-(thymin-1-yl)-butyric acid
      methyl ester.

PMID- 11990560
TI  - Coated-wire silver ion-selective electrode based on silver complex of cyclam.
AB  - A coated-wire ion-selective electrode (ISE) based on cyclam (1,4,8,11
      tetraazacyclotetradecane) as a neutral carrier in a polyvinyl chloride (PVC)
      matrix was fabricated for the determination of Ag(I) ions. The coated-wire ISE
      exhibited a linear Nernstian response over the range 1 x 10(-1) to 1 x 10(-7) M
      with a slope of 59 +/- 2 mV per decade change and a detection limit of 5 x 10(-8)
      M. The ISE shows a greater preference for Ag over other cations with good
      precision. The electrode was selective towards Ag(I) ions in the presence of 13
      different metal ions tested. The selectivity coefficients (K(ij)) were determined
      for Na(I), K(I), Mg(II), Ca(II), Ba(II), Mn(II), Co(II), Ni(II), Cu(II), Zn(II),
      Cd(II), Pb(II) and Hg(II). The selectivity coefficients of these cations are in
      the range of 10(-4) to 10(-2). This ISE was used for the determination of free
      silver and total silver in electroplating bath solutions, additives and
      brighteners.

PMID- 11990561
TI  - Cyclic voltammetric measurements of growth of Aspergillus terreus.
AB  - A detailed study using the cyclic voltammogram was done on the live cells of
      Aspergillus terreus. The peak current values were obtained for different days of
      growth and plotted against time. The response of cyclic voltammogram showed the
      phases of the growth of the fungus. The growth curve obtained matched well with
      the conventional methodology, which assesses the increase of dry weight of the
      organisms against time. The electrochemical method is more advantageous because
      it is easy to assess and consumes less time. Further the electrochemical method
      clearly shows the decline phase which is generally not very defined in the
      conventional method of assessment of the growth curve. It was confirmed by
      further experiments that the metabolites were responsible for the anodic peak and
      not the biomass. Further work is in progress in order to analyze the
      metabolite(s) that is/are responsible for the anodic peak.

PMID- 11990562
TI  - Development of a new matrix based on a silicone ladder polymer for ion-sensing
      membranes.
AB  - A silicone ladder-type polymer was successfully utilized for a matrix of an ion
      sensing membrane to fabricate an ion-sensitive field-effect transistor. An ion
      sensing membrane was readily fabricated by mixing a silicone ladder-type oligomer
      with a quaternary ammonium salt, casting onto the gate of the field-effect
      transistor, and polymerizing with heating. Since no acid catalysts were needed to
      prepare the ion sensing membrane, it was possible to keep the quaternary ammonium
      salt in the matrix without decomposition. The ion-sensitive field-effect
      transistor based on the silicone ladder-type polymer and the quaternary ammonium
      salt showed a linear response with a slope of -58.1 mV decade(-1) very close to
      the theoretical Nernstian response over an NO3- range between 3.0 x 10(-6) and
      1.0 x 10(-1) M. The time required to reach 90% total response was within 5 s,
      when the NO3- concentration was changed from 1.0 x 10(-3) to 3.0 x 10(-3) M. The
      newly fabricated ion-sensitive field-effect transistors have kept their original
      sensitivity for more than half a year.

PMID- 11990564
TI  - Simultaneous determination of nitrate and nitrite in saliva and foodstuffs by non
      suppressed ion chromatography with bulk acoustic wave detector.
AB  - In the present paper, nitrate and nitrite in foodstuffs and saliva were
      simultaneously determined using a non-suppressed ion chromatography (IC) method
      with a bulk acoustic wave sensor (BAW) as detector, and 1.5 mmol/L potassium
      hydrogenphthalate (KHP) as mobile phase. The IC-BAW method is simple, rapid and
      accurate. The determination limits for nitrite and nitrate are 0.20 and 0.30
      mg/L, respectively. The IC-BAW is comparable and agrees with the conventional
      spectrophotometric method for nitrite and nitrate determination.

PMID- 11990563
TI  - Selective transport of silver ion through a supported liquid membrane using
      hexathia-18-crown-6 as carrier.
AB  - A facile supported liquid membrane (SLM) system for the selective and efficient
      transport of silver ion is introduced. The SLM used is a thin porous
      polyvinyldifluoride membrane impregnated with hexathia-18-crown-6 (HT18C6)
      dissolved in nitrophenyloctyl ether. HT18C6 acts as a specific carrier for the
      uphill transport of Ag+ ion as its picrate ion paired complex through the SLM. In
      the presence of thiosulfate ion as a suitable stripping agent in the strip
      solution, transport of silver occurs almost quantitatively after 4 h. The
      selectivity and efficiency of silver transport from aqueous solutions containing
      other Mn+ cations such as Mg2+, Ca2+, Co2+, Ni2+, Cu2+, Zn2+, Pb2+, Cd2+, Hg2+,
      Fe3+ and Cr3+ ions were investigated.

PMID- 11990565
TI  - HPLC/UV analysis of proteins in dairy products using a hydrophobic interaction
      chromatographic column.
AB  - High-performance liquid chromatography using a Chrompack P-300-RP column
      containing a polystyrene-divinylbenzene copolymer-based packing was examined to
      analyze bovine milk protein components. The separation of major raw-milk proteins
      could be performed rapidly and reliably with this HPLC/UV method. The
      determinations were performed in the linear ranges of 0.01-2.0 mg/ml for alpha
      lactalbumin, 0.04-2.5 mg/ml for caseins and 0.02-2.0 mg/ml for beta
      lactoglobulin. The validity of the method was verified. Since the chromatographic
      column enabled the quantification of only "native" milk proteins, the extent of
      denaturation and loss of milk proteins could be examined. Thus, evaluation of
      heat-induced proteins denaturation was carried out in raw milk heated for 5 min
      at pre-determined temperatures.

PMID- 11990567
TI  - Normal-phase HPLC separation of possible biosynthetic intermediates of pheophytin
      a and chlorophyll a'.
AB  - Normal-phase HPLC conditions have been developed for separating the C17(3)
      isoprenoid isomers, which are expected to be formed as biosynthetic intermediates
      of chlorophyll (Chl) a, Chl a' (C13(2)-epimer of Chl a), pheophytin (Pheo) a and
      protochlorophyll (PChl). The application of these conditions to pigment
      composition analysis of greening etiolated barley leaves allowed us to detect,
      for the first time, the C17(3) isomers of Chl a', a possible constituent of the
      primary electron donor of photosystem (PS) I, P700, and those of Pheo a, the
      primary electron acceptor of PS II, in the very early stage of greening. The
      C17(3) isomer distribution patterns were approximately the same between Chl a and
      Chl a', but significantly different between Pheo a and Chl a', probably
      reflecting the similarity and difference, respectively, in the biosynthetic
      pathways of these pigment pairs.

PMID- 11990566
TI  - Separation and determination of minor photosynthetic pigments by reversed-phase
      HPLC with minimal alteration of chlorophylls.
AB  - Reversed-phase HPLC conditions for separation of chlorophyll (Chl) a, Chl a' (the
      C132-epimer of Chl a), pheophytin (Pheo) a (the primary electron acceptor of
      photosystem (PS) II), and phylloquinone (PhQ) (the secondary electron acceptor of
      PS 1), have been developed. Pigment extraction conditions were optimized in terms
      of pigment alteration and extraction efficiency. Pigment composition analysis of
      light-harvesting complex II, which would not contain Chl a' nor Pheo a, showed
      the Chl a'/Chl a ratio of 3-4 x 10(-4) and the Pheo a/Chl a ratio of 4-5 x 10(
      4), showing that the conditions developed here were sufficiently inert for Chl
      analysis. Preliminary analysis of thylakoid membranes with this analytical system
      gave the PhQ/Chl a' ratio of 0.58 +/- 0.03 (n = 4), in line with the
      stoichiometry of one molecule of Chl a' per PS I.

PMID- 11990568
TI  - Examination of the best pressure range for ion/molecule reactions of
      anthraquinones in an external source ion trap mass spectrometer.
AB  - This study outlines some observations of the pressure effect for gas phase ion
      molecule reactions of anthraquinone derivatives with dimethyl ether in an
      external source ion trap mass spectrometer. At the reagent pressure of 7.998 x
      10(-2) Pa, formation of the protonated ions, [M + 13]+, [M + 15]+, and [M + 45]+
      ions, of anthraquinones can be observed. However, at the pressure of 1.066 x 10(
      2) Pa, formation of molecular ions and many fragment ions of the M+. or [M + H]+
      ions have been observed. Since the pressure effect is notable within a small
      range of pressures for many compounds, it is important to draw attention to the
      use of the ion trap with an external source where other factors such as ion
      source residence time may play a role. This can also provide some information for
      better and more careful controls of the reagent pressure in order to obtain fair
      CI spectra in an external source ion trap mass spectrometer.

PMID- 11990569
TI  - Distribution analysis of epoxy groups in polymers by derivatization-electron
      probe X-ray microanalysis.
AB  - An analytical method, referred to as "derivatization-electron probe X-ray micro
      analysis (XMA)", has been developed to determine the distribution of a small
      amount of the functional groups in a polymer. The suitable conditions for the
      derivatization reaction with epoxy groups, which contribute to the hardening
      reactions of polymers, were investigated. It was found that epoxy groups in
      polymers were derivatized selectively using gas-phase esterification with
      hydrochloric acid (HCI). The most suitable amount of HCl in a 50 ml vial was 300
      microl. After setting a sample in the vessel without directly contacting the
      reagent, by reacting the reagent and the sample at 25 degrees C for 1 h, the
      highest reaction yield and selectivity were obtained. By derivatization-XMA using
      this reaction condition, the measurement of the distribution of epoxy groups in
      the polymer became feasible. Actual applications to a depth analysis of epoxy
      groups in the hardened acrylic coating and epoxy resin proved that this method is
      useful for the characterization of polymers and for the study of the hardening
      reaction of polymers.

PMID- 11990570
TI  - A new approach of direct sample-digestion before vaporization for determination
      of a metal in rocks by inductively coupled plasma atomic emission spectrometry.
AB  - A new approach to sample digestion, subsequent vaporization and introduction to
      an inductively coupled plasma (ICP) atomic emission spectrometer was developed
      for the direct determination of magnesium. To each small sample cuvette made of
      tungsten, a ground rock sample was precisely weighed. The cuvette was situated on
      a tungsten boat furnace. Ammonium fluoride solution was added to the cuvette as a
      chemical modifier. After the on-furnace digestion has been completed, the
      analyte, magnesium, in the cuvette was vaporized and introduced into the ICP
      atomic emission spectrometer. Since the powdered samples were wet-digested in the
      sample cuvettes prior to vaporization, they could be analyzed by using a
      calibration curve prepared from aqueous standard solutions. This method was
      applied to the determination of magnesium in several standard reference materials
      with satisfactory results.

PMID- 11990571
TI  - Determination of beryllium and selenium in human urine and of selenium in human
      serum by graphite-furnace atomic absorption spectrophotometry.
AB  - For human urine beryllium (Be), each sample (500 microl) was diluted (1+1) with
      Nash reagent (containing 0.2% (v/v) acetylacetone and 2.0 M ammonium acetate
      buffer at pH 6.0) and then a 20-microl volume of Triton X-100 (0.4%, v/v) aqueous
      solution was added. An aliquot (10 microl) of the diluted urine mixture was
      introduced into a graphite cuvette and was atomized according to a temperature
      program. The method detection limit (MDL, 3sigma) for Be was 0.37 microg/l in the
      undiluted urine sample and the calibration graph was linear up to 65.0 microg/l.
      Calibration graphs were prepared by the standard addition method. Accuracies of
      98.6-102% were obtained when testing standard reference material (SRM 2670)
      freeze dried human urine samples. Precision (relative standard deviation, RSD)
      for urine Be was < or = 2.3% (withinrun, n = 5) and was < or = 3.0% (between-run,
      n = 3). For human urine and serum selenium (Se), samples (100 microl) were
      diluted with HNO3 (0.2%, v/v) to make a (1+1) dilution for urine analysis or a
      (1+4) dilution for serum analysis. An additional aliquot (10 microl) of Triton X
      100 (0.1%, v/v) was added to each 200 microl of (1+1) diluted urine (or 20 microl
      of the Triton X-100 was added to each 500 microl of (1+4) diluted serum) sample.
      After the diluted sample mixture (10 microl) was introduced into a graphite
      cuvette, the corresponding chemical modifier (10 microl, containing Ni2+ + Pd +
      NH4NO3 in HNO3 (0.2%, v/v)) was added to it and the mixture was atomized. The MDL
      (3sigma) for Se in urine and in serum was 4.4 and 21.4 microg/l in undiluted
      sample, respectively, and the calibration graphs were linear up to 150 and 400
      microg/l. Accuracies of urine Se were 98.9 - 99.4% by testing SRM 2670 (NIST)
      urine standards with RSD (between-run, n = 3) within 2.9%; and that of serum Se
      was 97.2% when testing a certified second-generation human serum (No. 29, #664)
      with RSD (between-run, n = 3) of 1.4%. The proposed method can be applied easily,
      directly, and accurately to the measurement of Be and Se in real samples
      (including six urine Se and four serum Se from patients of Blackfoot Disease in
      Taiwan).

PMID- 11990572
TI  - Spectrophotometric determination of certain vicinal dihydroxybenzene derivatives
      in pharmaceutical preparations.
AB  - A simple, rapid and sensitive spectrophotometric method for the assay of certain
      adrenergic drugs, [pyrocatechol (PC), levodopa (LD), methyldopa (MD) and dopamine
      (DP)] is described. The method involves the oxidation of o-dihydroxybenzene
      derivatives by K2CrO4 followed by oxidative coupling with sulfanilic acid (SPA),
      leading to the formation of a red or violet colored product having maximum
      absorbance at 490-495 nm for LD, MD and DP or at 560 nm for PC. This method has
      been successfully applied to the determination of LD, MD and DP in tablets and
      injections of pharmaceutical preparation. The common excipients do not interfere
      with the proposed method. A statistical comparison of these results with those of
      a reported method shows good agreement and indicates no significant difference in
      precision.

PMID- 11990573
TI  - Fluorescent derivatization of nitrite ions with 2,3-diaminonaphthalene utilizing
      a pH gradient in a Y-shaped microchannel.
AB  - The on-chip derivatization of nitrite ions with 2,3-diaminonaphthalene (DAN)
      utilizing a pH gradient formed in a Y-shaped microchannel was investigated.
      Nitrite ions react with DAN at low pH, and strongly fluoresced at high pH.
      Therefore, a reaction at low pH followed by the addition of a strong alkaline
      solution is the usual procedure in a batch scheme. However, a strong alkaline
      solution, like an NaOH aqueous solution, erodes the wall of the microchannels in
      substrates made of glass or polymers, and has not been considered suitable for
      use in microchannels. We first investigated the derivatization reaction and
      fluorescent properties of nitrite ions with DAN. We found that the on-chip
      fluorescent derivatization reaction and detection without the addition of an
      alkaline solution is possible by controlling the pH values of the nitrite
      solution and the DAN solution to form a suitable pH gradient by utilizing a
      buffering effect of triethanolamine solution, which is used as an NO2 gas
      absorption medium. These results have suggested the feasibility of novel reaction
      schemes which can provide the desired products due to a controlled pH gradient in
      the microchannels, as well as the possibility of an on-site monitoring microchip
      device for ambient NO2.

PMID- 11990574
TI  - Fluorescence enhancement of coumarin-6-sulfonyl chloride amino acid derivatives
      in cyclodextrin media.
AB  - Coumarin-6-sulfonyl (6-CS) amino acid derivatives form inclusion complexes with a
      and /-cyclodextrins (CD) in aqueous solution. The stoichiometry of the inclusion
      complex and the equilibrium constant were investigated. Using a fluorescence
      technique and alanine-beta-CD as a model, a 1:2 guest-host complex was
      established, and K = 4.7 x 10(5) mol(-2) l(2) was obtained. Fluorescence
      enhancement was observed for all derivatives studied, with glycine exhibiting a
      greater enhancement, and tyrosine showing the least. The stability of the
      inclusion complex was found to depend on the respective sizes of the guest-host
      complex and their interaction.

PMID- 11990575
TI  - Spectroelectrochemical characterization of Si-bridged diphenylamines: influence
      of Si-bridging upon electronic structures of diphenylamines.
AB  - Spectroelectrochemical properties of monosilane bridged diphenylamine (5,10
      dihydro-2,8-diphenyl-5, 10,10-trimethylphenazasiline, Phenaz) and disilane
      bridged diphenylamine (2,8-diphenyl-10,11-dihydro-10,11-disila-5,10,10,11,11
      pentamethyldibenzo[b,f]azepine, DSiAzep) were investigated. The electrochemical
      oxidation of Phenaz was reversible and its cyclic voltammogram was almost the
      same shape as that of diphenylamine (DPA). The electrochemical oxidation of
      DSiAzep was followed by irreversible reactions leading to the cleavage of the Si
      Si bond. On electrochemical oxidations of Phenaz and DPA, the formation of a
      stable radical cation was observed with UV-Vis spectroscopy. In comparison with
      the absorption characteristics of oxidized radical cations, it was seen that the
      oxidized radical cation of Phenaz was more delocalized than that of DPA. In the
      same way, absorption characteristics of oxidized DSiAzep were observed to be
      different from those observed in Phenaz and DPA.

PMID- 11990576
TI  - Rapid determination of chemical oxygen demand (COD) using focused microwave
      digestion followed by a titrimetric method.

PMID- 11990577
TI  - Determination of the molecular mass of new L-fucose-containing glycosaminoglycan
      and its distribution by high-performance gel-permeation chromatography with laser
      light-scattering detection.

PMID- 11990578
TI  - Evaluation of dissolution methods in the presence of high chloride content for
      the determination of germanium in geological matrices by hydride generation
      atomic absorption spectrometry.

PMID- 11990579
TI  - Spectrophotometric and AAS determinations of trace zinc(II) in natural waters and
      human blood after preconcentration with phenanthraquinone
      monophenylthiosemicarbazone.

PMID- 11990580
TI  - Crystal structure of bis(diphenylphosphino)ethane bis(2
      selenopyridinato)platinum(II).

PMID- 11990582
TI  - Crystal structure of [bis[N-(2-hydroxyethylamino)ethylsalicylaldiminato]
      iron(III)] chloride.

PMID- 11990583
TI  - Crystal structure of (2,2'-bipyridine-N,N')(1,4,7,10-tetraazacyclododecane
      N,N',N",N''')nickel(II) diperchlorate.

PMID- 11990581
TI  - Crystal structure of 2-[(5',6',7',8'-tetrahydro-5',5',8',8'-tetramethyl)-2'
      naphthyl]-1-ethyl-1H-benzimidazole-5-carboxylic acid ethyl ester.

PMID- 11990584
TI  - Crystal structure of Cs(18-crown-6)I x 2H2O.

PMID- 11990585
TI  - Determination of lomefloxacin, an antibacterial drug, in pharmaceutical
      preparations based on its polarographic catalytic wave in the presence of 2
      iodoacetamide.
AB  - In a 0.125 mol/L phosphate (pH 6.6)/2.5 x 10(-4) mol/L 2-iodoacetamide solution,
      lomefloxacin yields a response of a polarographic catalytic current. The second
      order derivative peak current of the catalytic wave of lomefloxacin is
      proportional to its concentration in the range of 1.0 x 10(-8)-1.0 x 10(-6) mol/L
      (r = 0.998). The sensitivity of the catalytic wave is 25-times higher than that
      of the corresponding reduction wave for 5.0 x 10(-7) mol/L lomefloxacin. The
      proposed method was applied to the determination of lomefloxacin in
      pharmaceutical preparations. The polarographic reduction wave is ascribed to a
      one-electron reduction of the C=C bond of lomefloxacin zwitterion accompanied by
      an acid-base equilibrium. The catalytic wave should be caused by regeneration of
      the lomefloxacin molecule at electrode surface due to the one-electron reduction
      product being further oxidized by electroreductive intermediate products of 2
      iodoacetamide.

PMID- 11990586
TI  - Ultrasensitive optical DNA biosensor based on surface immobilization of molecular
      beacon by a bridge structure.
AB  - A novel biotinylated molecular beacon (MB) probe was developed to prepare a DNA
      biosensor using a bridge structure. MB was biotinylated at the quencher side of
      the stem and linked on a biotinylated glass cover slip through streptavidin,
      which acted as a bridge between MB and glass matrix. An efficient fluorescence
      microscope system was constructed to detect the fluorescence change caused by the
      conformation change of MB in the presence of complementary DNA target. The
      proposed biosensor was used to directly detect, in real-time, the target DNA
      molecules. The bridge immobilization method caused the proposed DNA biosensor to
      have a faster and more stable response. Under the optimal conditions, the newly
      developed DNA biosensor showed a linear response toward ssDNA in the range of 5
      100 nM with a detection limit of 2 nM. It was interesting to note that the
      described biosensor was reproducible after being regenerated by urea.

PMID- 11990589
TI  - Electrocatalytic reduction of dioxygen on a glassy carbon electrode modified with
      adsorbed cobaloxime complex.
AB  - The preparation and electrochemical properties of a glassy carbon (GC) electrode
      modified with cobaloxime complex were investigated. The complex of the type
      [CoIII(DO)(DOH)pn)Cl2] where (DO)(DOH)pn = N2,N2'-propanediylbis-2,3-butanedione
      2-imine-3-oxime) was adsorbed irreversibly and strongly on the surface of
      preanodized glassy carbon electrode. Electrochemical behavior and stability of
      modified GC electrode were investigated by cyclic voltammetry. The
      electrocatalytic reduction of dioxygen has been studied using this modified
      glassy carbon electrode by cyclic voltammetry, chronoamperometry and rotating
      disk electrode voltammetry as diagnostic techniques. The modified electrode
      showed excellent eletrocatalytic ability for the reduction of dioxygen to
      hydrogen peroxide in acetate buffer (pH 4.0) with overpotential 1.0 V lower than
      the plain glassy carbon electrode. The formal potential for this modified
      electrode is not shifted to more negative potentials by repeated reduction
      oxidation cycles in oxygen-saturated supporting electrolyte solution. The
      apparent electron transfer rate constant (kS), the transfer coefficent (alpha)
      and the catalytic rate constant of O2 reduction at a GC modified electrode were
      determined by cyclic voltammetry and rotating disk electrode voltammetry and were
      found to be around 2.6 s(-1), 0.33 and 2.25 x 10(4) M(-1) s(-1). Based on the
      results, a catalytic mechanism is proposed and discussed.

PMID- 11990587
TI  - Methylcellulose-immobilized reversed-phase precolumn for direct analysis of drugs
      in plasma by HPLC.
AB  - We evaluated a new restricted access media (RAM) precolumn for direct analysis of
      drugs in plasma using a column switching HPLC system. The new RAM material was
      prepared by the modification of the external surface of porous silica with
      hydrophilic methylcellulose (MC), followed by modification of the internal
      surface with octadecylsilane (ODS). The external surface of the MC-immobilized
      ODS silica material (MC-ODS) suppressed the adsorption of proteins, while the
      internal surface of MC-ODS retained various types of drugs, such as ketoprofen,
      propranolol, caffeine and atenolol in plasma samples. In addition, MC-ODS allowed
      direct analysis of drugs in a 1000-microL plasma sample to monitor trace amounts
      of analytes contained. Reduced efficiency and clogging of the MC-ODS precolumn
      and/or the analytical column were not observed even after the repetitive
      injection of plasma sample up to 40 mL. Our results indicated that the MC-ODS
      precolumn could be used in pharmacodynamic and clinical studies.

PMID- 11990588
TI  - Flow-through chemiluminescence sensor using immobilized histamine oxidase from
      Arthrobacter crystallopoietes KAIT-B-007 and peroxidase for selective
      determination of histamine.
AB  - A flow sensor with immobilized oxidases is proposed for the determination of
      histamine in fish meat. Chemiluminometric measurement of histamine was based on
      the luminol reaction with hydrogen peroxide produced by immobilized histamine
      oxidase (EC 1.4.3.-.) and peroxidase (EC 1.11.1.7.) within a flow cell. Histamine
      oxidase was found in cells of Arthrobacter crystallopoietes KAIT-B-007 isolated
      from soil. The oxidase and peroxidase were coimmobilized covalently on tresylated
      hydrophilic vinyl polymer beads and packed into transparent PTFE; the tubing was
      used as the flow cell. One assay for histamine was done at intervals of 2 min
      without carryover. The calibration curve for histamine was linear from 0.1 microM
      to 50 microM. The response was reproducible within 1.25% of the relative standard
      deviation for 115-replicate injections of 50 microM histamine. The sensor system
      was applied to the determination of histamine in fish meat extracts.

PMID- 11990590
TI  - Ion-channel sensing of ferricyanide anion based on a supported bilayer lipid
      membrane.
AB  - Ferricyanide anion has usually been used as a marker of ion-channel sensors. In
      this work we first found that ferricyanide, itself, can act as a stimulus to
      regulate the permeability of sBLM prepared from didodecyldimethylammonium bromide
      (a kind of synthetic lipid) on a GC electrode. We used cyclic voltammetry and
      a.c. impedance to investigate this phenomenon. The interaction between sBLM and
      ferricyanide concerns time. Furthermore, we developed a sensor for ferricyanide
      anion. The ion-channel sensor is highly sensitive. It can detect ferricyanide
      concentration as low as 5 microM.

PMID- 11990591
TI  - Highly selective iodide-sensing silicone ladder polymer membranes containing a
      porphyrin and a quaternary ammonium salt.
AB  - It has been demonstrated that a glass-like silicone ladder-type polymer permits
      one to homogeneously incorporate high amounts of ionophores into the covalently
      bonded double chain structure. Furthermore, by making use of this feature, we
      have successfully fabricated an iodide ion-sensitive field-effect transistor
      based on two kinds of ionophores and silicone ladder polymer matrix. As
      ionophores, 5,10,15,20-tetraphenyl-21H,23H-porphyrin and dimethyloctadecyl-3
      trimethoxylsilylpropylammonium chloride were homogeneously incorporated into the
      matrix. The ion-sensitive field-effect transistor showed a linear potential
      response ranging in the I- concentration between 1.0 x 10(-5) and 1.0 x 10(-1) M.
      The selectivity coefficients for I- towards interferences of ClO4- and NO3- were
      estimated to be Kpot(I-,ClO4-) approximately 6.2 x 10(-4) and Kpot(I-,No3-)
      approximately 4.9 x 10(-4). The matrix has proved to be so stable that the
      selectivity coefficients have not been altered over six months.

PMID- 11990593
TI  - Enantiomer separation of mandelates and their analogs on cyclodextrin derivative
      chiral stationary phases by capillary GC.
AB  - Enantiomer separation of mandelates and their analogs, which are important
      intermediates in asymmetric synthetic and pharmaceutical chemistry, was
      investigated by capillary gas chromatography using different cyclodextrin
      derivative chiral stationary phases (CD CSPs). The used cyclodextrin derivatives
      included permethylated beta-CD (PMBCD), permethylated gamma-CD, heptakis(2,6-di-O
      butyl-3-O-butyryl)-beta-CD, heptakis(2,6-di-O-pentyl-3-O-acetyl)-beta-CD and
      heptakis(2,6-di-O-nonyl-3-O-trifluoroacetyl)-beta-CD (DNTBCD), respectively.
      Among all the CSPs used, PMBCD and DNTBCD exhibited the broadest and best
      enantioselectivity for all the racemates investigated. Some thermodynamic
      parameters were evaluated and an enthalpy-entropy compensation effect was
      observed in enantiomer separation processes of mandelates and their analogs.
      Based on thermodynamic data and molecular mechanics calculations, the chiral
      recognition mechanism of mandelate derivatives on CD CSPs is discussed.

PMID- 11990592
TI  - Matrix effect on the analysis of oligonucleotides by using a mass spectrometer
      with a sonic spray ionization source.
AB  - Matrix or impurities remaining in a DNA sample solution after various sample
      treatment procedures may influence a subsequent DNA analysis. In this work,
      several matrices were investigated concerning their effects on the analysis of
      oligonucleotide by using an ion-trap mass spectrometer equipped with a sonic
      spray ionization source. Inorganic salts of sodium chloride and magnesium
      chloride depressed the signal intensity by about 50% when the content of the
      salts was about 10 microM. dNTPs and Taq showed more severe depression on the
      oligonucleotide. However, Tris, or (hydroxymethyl)aminomethane, intensified the
      signal intensity, if its content was within an appropriate range. When the
      content of Tris was about 500 microM, the signal intensity was enhanced by
      factors of 3 and 5 for the 6-mer and the 20-mer oligonucleotides, respectively.
      With the existence of Tris, matrix effects from the inorganic salts, dNTPs and
      Taq were reduced.

PMID- 11990594
TI  - Indirect spectrophotometric determination of small amounts of selenium(IV) and
      arsenic(V) by simple extraction using flotation columns.
AB  - A simple, rapid and selective procedure for the indirect spectrophotometric
      determination of Se(IV) and As(V) has been developed. It is based on the
      reduction of Se(IV) to Se(0) and As(V) to As(III) with hydroiodic acid (KI +
      HCl). The liberated iodine, equivalent to each analyte, is quantitatively
      extracted with oleic acid (HOL) surfactant. The iodine-HOL system exhibits its
      maximum absorbance at 435 nm. The different analytical parameters affecting the
      extraction and determination processes have been examined. The calibration graphs
      were found to be linear over the ranges 5-120 and 0.25-20 ppm of Se(IV) and
      As(V), with lower detection limits of 2.5 and 0.15 ppm and molar absorptivities
      of 1 x 10(4) and 0.5 x 10(4) dm3 mol(-1) cm(-1), respectively. Sandell's
      sensitivity was calculated to be 0.0078 and 0.0149 microg/cm2 in the same order.
      The relative standard deviation for five replicate analyses of 40 ppm Se(IV) and
      4 ppm As(V) were 1.0 and 0.9%, respectively. The proposed procedure in the
      presence of EDTA as a masking agent for foreign ions has been successfully
      applied to the determination of Se(IV) in a reference sample and As(V) in copper
      metal, in addition to their determination in spiked and polluted water samples.

PMID- 11990596
TI  - Spectrophotometric determination of periodate, iodate and bromate mixtures based
      on their reaction with iodide.
AB  - A rapid, simple, precise and accurate method is proposed for the determination of
      ternary mixtures of periodate-iodate-bromate based on their reaction with iodide
      ion at different pH values. The absorbance was measured at 352 nm. Three sets of
      reaction conditions were developed. In the first set of conditions, only
      periodate reacted with iodide, but in the second set the periodate and iodate
      reacted with iodide and in the third set the three ions reacted with iodide
      during the first 3 min after initiation of the reaction. The method could be used
      for individual determinations of periodate, iodate and bromate in the
      concentration range of 0.05-8.0 microg/ml, 0.05-5.0 microg/ml and 0.2-12
      microg/ml, respectively. The data were evaluated by simultaneous equations.

PMID- 11990595
TI  - Determination of trace amounts of copper(II) by using catalytic redox reaction
      between methylene blue and ascorbic acid.
AB  - A sensitive and selective kinetic-spectrophotometric method is proposed for the
      determination of microg mL(-1) amounts of Cu2+ based on its catalytic effect on
      the oxidation of L-ascorbic acid by Methylene Blue in a strongly acidic medium.
      The reaction is monitored spectrophotometrically by measuring the decrease in
      color intensity of Methylene Blue at 665 nm. The analysis of Cu2+ ion is
      performed by a fixed-time method. At a given time of 2 min at pH 2.20 and 32
      degrees C, the detection limit is 10 ng mL(-1) and the relative standard
      deviation for 0.4 microg mL(-1) Cu2+ is 3.60% (n = 6). The method is free from
      most of the interferences and the effect of diverse ions on the determination of
      Cu2+ is also reported. The proposed method is virtually specific to copper and
      has been satisfactorily applied to its determination in electric copper wire
      samples and pharmaceutical products. Results were also verified by the atomic
      absorption spectrometry technique (AAS).

PMID- 11990597
TI  - Multiwavelength spectrophotometric resolution of the micro-equilibria of
      cetirizine.
AB  - The acid-base properties of the antihistamine (H1 receptor antagonist) cetirizine
      have been studied by using a previously developed multiwavelength
      spectrophotometric titration method. A new computational procedure called "Two
      Step-Divide-and-Conquer" (TSDC), which applied evolving factor analysis (EFA) and
      target factor analysis (TFA), has been derived to unravel the micro-equilibria of
      the triprotic zwitterionic compound from the spectral data. We have demonstrated
      that a single spectrophotometric titration experiment is sufficient to determine
      the 12 unknown microconstants and the distribution of microspecies, which are in
      good agreement with literature values, where available.

PMID- 11990599
TI  - Observation and application of a pattern in a DNA-histone mixture.

PMID- 11990598
TI  - Determination of menadione sodium bisulfite in pharmaceutical preparations by
      flow-injection on-line photochemical spectrofluorometry.
AB  - A flow-injection on-line photochemical spectrofluorometry (FI-PF) was developed
      for the determination of menadione sodium bisulfite (MSB) using acetone and
      sodium sulfite as sensitizing reagents. An injected sample band carried by a
      water stream was on-line merged with a mixed NaOH, Na2SO3 and acetone solution in
      a "T" connector. It was then driven to pass a knotted PTFE photochemical reactor
      (0.5 mm i.d. x 200 cm, KR) that was freely coiled around a 6-W low-pressure
      mercury lamp. While passing the KR, MSB was derived into an intensively
      fluorescent compound that was on-line delivered into a flow-through cell and
      detected therein at an emission wavelength of 459 nm and an excitation wavelength
      of 336 nm. Under optimized conditions a detection limit of 0.38 microg l(-1) was
      achieved at a sampling rate of 90 h(-1). Eleven determinations of 0.5 mg l(-1)
      and 0.05 mg l(-1) MSB standard solution gave RSDs of 0.75% and 1.3%,
      respectively. The calibration curve was linear in the MSB concentration range
      0.005-1.5 mg l(-1). The proposed method was successfully applied to assay the MSB
      content in MSB injection.

PMID- 11990600
TI  - Evaluation of zirconium(IV) complex with N-dodecyliminodiacetate as an
      anionophore for ion-selective electrodes.

PMID- 11990601
TI  - Optimum concentration of anionic sites in lipophilic macrocyclic pentaamine-based
      liquid membranes for potentiometric responses to anionic analytes.

PMID- 11990602
TI  - GC/MS determination of phenolic compounds in soil samples using Soxhlet
      extraction and derivatization techniques.

PMID- 11990604
TI  - Magnetophoretic behavior of single polystyrene particles in aqueous manganese(II)
      chloride.

PMID- 11990603
TI  - Determination of 16 priority polycyclic aromatic hydrocarbons in particulate
      matter by HRGC-MS after extraction by sonication.

PMID- 11990605
TI  - Simultaneous estimation of geniposide and genipin in mouse plasma using high
      performance liquid chromatography.

PMID- 11990606
TI  - Crystal structure of [triaqua(salicylato)(nicotinamide)zinc(II)] salicylate.

PMID- 11990607
TI  - Crystal and molecular structure of dimethyl 3-methoxy-4-isopropylpent-2
      enedioate; a synthetic intermediate to the espintanol.

PMID- 11990608
TI  - Crystal structure and synthesis of 17alpha-hexanoyloxy-16beta-methylpregna-4,6
      diene-3,20-dione.

PMID- 11990609
TI  - Crystal structure of (+)-(R)-3-methyl-1-(1'-phenyl-ethyl)-1H-pyridin-2-one.

PMID- 11990610
TI  - Crystal structure of 3,4-diphenyl-N-(2,6-bis(isopropyl)phenyl)pyrrole-2,5-dione.

PMID- 11990611
TI  - Chemical sensor based on nonlinearity: principle and application.
AB  - Novel chemical sensors based on a time-dependent nonlinear response are reviewed.
      The strategy is to artificially mimic information transduction in living
      organisms. In taste and olfaction, information of chemical structure and
      concentration is transformed into nervous impulses in the nervous cell, i.e.,
      time-dependent multi-dimensional information. Because the excitation and pulse
      generation in the nervous cell are typically nonlinear phenomena, it may be
      worthwhile to utilize the nonlinearity as the multi-dimensional information for
      molecular recognition. The principle of a "nonlinear" sensor is that a sinusoidal
      modulation is applied to a system, and the output signal is analyzed. The output
      signal of the sensor is characteristically deformed from the sinusoidal input
      depending on the chemical structure and concentration of the chemical stimuli.
      The characteristic nonlinear responses to chemical stimuli are discussed in
      relation to the kinetics of chemical compounds on the sensor surface. As a
      practical application, we introduced electrochemical sensors based on the
      differential capacitance, semiconductor gas sensors under the application of
      sinusoidal temperature or diffusion change, and a chemical sensor based on the
      spatio-temporal information. We demonstrated that mutli-dimensional information
      based on nonlinearity can provide quite useful information for the analysis of
      chemical species, even in the presence of another analyte or an interference with
      a single detector.

PMID- 11990612
TI  - Fluorometric determination of N-nitroso-N-methylurea with nicotinamide and
      acetophenone.
AB  - A fluorometric method for the determination of N-nitroso-N-methylurea (NMU) has
      been developed. It is based on the N-methylation reaction of nicotinamide with
      NMU and a subsequent condensation reaction with acetophenone, followed by an acid
      treatment to form a fluorescent 2,7-naphthyridine derivative. This method enabled
      the determination of NMU in the range 0.05 - 2 nmol/200 microl with a relative
      standard deviation of ca. 3%. It was applied to the determination of NMU formed
      from a precursor N-methylurea (MU) under simulated gastric conditions containing
      nitrite and thiocyanate ions at pH 3.0 in the presence of fresh orange juice and
      milk. NMU was extracted by an Extrelut 20 column and then determined. The mean
      recoveries of NMU added to the simulated gastric juice containing water, orange
      juice and milk were 86.5, 85.1 and 69.8%, respectively. The amounts of NMU formed
      from MU were found to decrease to below 25% in the presence of orange juice and
      milk.

PMID- 11990614
TI  - Novel biosensor for the rapid measurement of estrogen based on a ligand-receptor
      interaction.
AB  - A bioaffinity sensor was developed aiming at the detection of estrogen. This
      biosensor system is based on the specific binding of estrogen to its receptor
      immobilized on a gold disk electrode. The recombinant DNA encoding human estrogen
      receptor ligand-binding domain was expressed in bacteria using the histidine-tag
      fusion system. The expression of the fusion protein was under control of a
      bacteriophage T7 promoter, and the protein was purified under native conditions
      by affinity chromatography, which is based on a specific interaction between a
      histidine-tag, located in the N-terminus of the protein, and the Ni(II) chelate
      adsorbent. The protein was immobilized on an Au-electrode with Ni(II)-mediated
      chemisorption using a histidine tag and thiol-modified iminodiacetic acid. Cyclic
      voltammetric measurements showed that the reversible electrochemical reaction of
      a ferrocyanide/ferricyanide redox couple was suppressed by the presence of
      estrogen in a concentration-dependent manner. It seems reasonable to suppose that
      the electrostatic property of the protein layer on the electrode surface was
      altered by complexation with estrogen. These data suggest that this biosensor is
      applicable to the evaluation binding activities of the chemicals toward the human
      estrogen receptor.

PMID- 11990613
TI  - Fluorescent molecular sensory system based on bis pyrene-modified gamma
      cyclodextrin dimer for steroids and endocrine disruptors.
AB  - A gamma-cyclodextrin dimer modified with two pyrene moieties, 6-(2-pyrenebutylate
      aminoethyl)pyrenebutylate-amino-6-deoxy-bis-gamma-cyclodextrin, has been
      synthesized in the presence of N,N'-dicyclohexycarbodiimide from gamma
      cyciodextrin dimer linked with ethylenediamine at an upper rim. The sensing
      ability and binding property of the titled dimer were investigated for bile acids
      and endocrine disruptors. This cyclodextrin dimer showed both monomer and excimer
      fluorescence; the guest-induced emissions were observed as increases or decreases
      depending on the guest. The values deltaI(m)/I0(m) and deltaI(ex)/I0(ex), where
      I0(m) and I(m) are fluorescence intensities of monomer emission in the absence
      and presence of a guest and I0(ex) and I(ex) are those of excimer emission and
      deltaI(m) and deltaI(ex) were I(m) - I0(m) and I(ex) - I0(ex), respectively, were
      used as a parameter of sensitivity. This host exhibited highly sensitive
      molecular recognition ability for bile acids and endocrine disruptors, in which
      the sensing parameters obtained from monomer emission were plus or minus values,
      whereas the parameters obtained as excimer emission were minus ones. The behavior
      of the appended moieties of the host during a host-guest complexation was studied
      by induced circular dichroism (ICD) and fluorescence spectra. The ICD intensities
      of the titled dimer were decreased upon an addition of a guest. The guest-induced
      variations in the fluorescence and ICD intensity suggest that the appended
      moieties move by altering the spatial relationship in the hydrophobic space
      between two linked cyclodextrins.

PMID- 11990615
TI  - Multielement determination and speciation of major-to-trace elements in black tea
      leaves by ICP-AES and ICP-MS with the aid of size exclusion chromatography.
AB  - A multielement determination of major-to-trace elements in black tea leaves and
      their tea infusions was carried out by ICP-AES (inductively coupled plasma atomic
      emission spectrometry) and ICP-MS (inductively coupled plasma mass spectrometry).
      Tea infusions were prepared as usual tea beverage by brewing black tea leaves in
      boiling water for 5 min. About 40 elements in tea leaves and tea infusions could
      be determined over the wide concentration range in 8 orders of magnitude. The
      extraction efficiency of each element was estimated as the ratio of its
      concentration in tea infusions to that in tea leaves. From the experimental
      results for the extraction efficiencies, the elements in black tea leaves were
      classified into three characteristic groups: (i) highly-extractable elements
      (>55%): Na, K, Co, Ni, Rb, Cs and Tl, (ii) moderately-extractable elements (20
      55%): Mg, Al, P, Mn and Zn, and (iii) poorly-extractable elements (<20%): Ca, Fe,
      Cu, Sr, Y, Zr, Mo, Sn, Ba and lanthanoid elements. Furthermore, speciation of
      major-to-trace elements in tea infusions was performed by using a combined system
      of size exclusion chromatography (SEC) and ICP-MS (or ICP-AES). As a result, many
      diverse elements were found to be present as complexes associated with large
      organic molecules in tea infusions.

PMID- 11990616
TI  - Multielement monitoring for dissolved and acid-soluble concentrations of trace
      metals in surface seawater along the ferry track between Osaka and Okinawa as
      investigated by ICP-MS.
AB  - Multielement monitoring of the concentrations of trace metals dissolved in
      surface seawater collected at sampling stations along the ferry track between
      Osaka and Okinawa was performed by ICP-MS (inductively coupled plasma mass
      spectrometry). The surface seawater samples were collected by an automated
      sampling system for on-board sampling, which was installed on the bottom of a
      ferryboat. A part of each seawater sample was filtered with a membrane filter
      (pore size of 0.45 microm) immediately after sampling. Both filtered and non
      filtered seawater samples were acidified to pH ca. 1 by adding conc. HNO3, and
      were subjected to chelating resin preconcentration for the determination of trace
      metals by ICP-MS, where the concentrations of analyte metals in the filtered and
      non-filtered seawater samples were referred to as the dissolved and total
      concentrations, respectively. According to the thus-obtained results, it was
      found that most trace metals, especially below the 0.01 microg l(-1) as the
      dissolved and total concentrations, sensitively reflected the environmental
      pollution in the Osaka Bay and Seto Inland Sea area, as well as near to the Bungo
      Canal and the outlet of Kagoshima Bay.

PMID- 11990617
TI  - Quantitative depth profiling of argon in tungsten films by secondary ion mass
      spectrometry.
AB  - Depth profiling of Ar in Ar-implanted tungsten (W) films with an excellent
      detection limit was investigated by secondary ion mass spectrometry (SIMS). Depth
      profiles of Ar with the detection of Ar+ and ArCs+ secondary ions, which were
      produced by O2+ and Cs+ primary ions, respectively, were compared in view of the
      detection limit and the depth resolution. The detection limit of Ar monitoring
      Ar+ was limited by the carbon- and oxygen-containing molecular ion (C2O+) in the
      sample as well as in the SIMS instrument. It was observed that some of the Ar+
      ions were produced in the vacuum above the sample surfaces, whereas the
      ionization of almost all C2O+ occurred at the samples. By using different energy
      spectra between Ar+ and C2O+, we showed that the energy-filtering technique is
      advantageous for suppressing C2O+ ion detection. It is also confirmed that the
      ArCs+ secondary ion is only slighting by the C2OCs+ mass-interference ion. A
      detection limit of 4 x 10(18) cm(-3) for monitoring Ar+ and 3 x 10(16) cm(-3) for
      monitoring ArCs+ was achieved under a primary-ion current density of 0.16 mA/cm2.
      The detection of ArCs+ ion rather than Ar+ was found to be superior in the
      detection limit and the depth resolution. We conclude that SIMS is useful for the
      determination of the Ar depth distribution in W films.

PMID- 11990618
TI  - Selective extraction of palladium(II) with theophylline derivatives.
AB  - Theophylline derivatives with some kinds of alkyl chains were synthesized and
      used in extraction experiments involving metal ions. Theophylline derivatives
      have exhibited a high selectivity for palladium over other precious metals and
      base metals. The extraction of palladium from acidic chloride media has been
      investigated using theophylline derivatives (= RN) as extractants. Palladium(II)
      was found to be extracted with 7-octyltheophylline according to the following
      reaction: PdCl2 + 2RN <==> PdCl2(RN)2. The extraction equilibrium constant was
      determined to be K = 2.67 x 10(8) ( moldm(-3))(-2). In addition, the stripping of
      palladium was performed to an extent of 100% by a single batchwise treatment with
      a 1.0 mol dm(-3) ammonia solution. The stoichiometric relation in the extraction
      of palladium was supported by an analysis using mass spectrometry.

PMID- 11990620
TI  - Hydration to benzo-15-crown-5, benzo-18-crown-6 and the benzo-18-crown-6
      potassium ion complex in the low-polar organic solvents.
AB  - The coextraction of water with benzo-15-crown-5 (B1SC5), benzo-18-crown-6 (B18C6)
      and the B18C6-K+ complex into seven low-polar solvents, i.e., carbon
      tetrachloride (CTC), chloroform (CF), dichloromethane (DCM), 1,2-dichloroethane
      (1,2-DCE), benzene (BZ), chlorobenzene (CB) and o-dichlorobenzene (o-DCB), has
      been investigated. The mean hydration number, nH2O, of these solutes in the water
      saturated organic solvents was determined. There is a trend that the nH2O values
      for any solutes increase with increasing the water concentration in the solvents.
      Those of B18C6 and B15C5 converge at almost 0.8 for B18C6 and 0.4 - 0.5 for B15C5
      in the solvents with the relatively high water concentration, i.e., CF, 1,2-DCE,
      DCM, and nitorobenzene (NB). The nH2O value of B15C5 is about one-half of that of
      B18C6 for a given organic solvent. The dominant species of the B18C6-K+ complex
      in these solvents is non-hydrated. From these results, the hydration equilibrium
      constants, KH2O, in the organic solvents were estimated.

PMID- 11990619
TI  - Thermodynamics of the distribution of some carboxylic acids between organic
      solvents and a perchlorate solution.
AB  - The distribution of formic, benzoic and 4-methylbenzoic acids between a 0.1 mol
      dm(-3) (Na+, H+)ClO4- solution and octanol and carbon tetrachloride was studied
      at five different temperatures of 10 - 30 degrees C. The thermodynamic parameters
      for the transfer process of monomeric acid between two phases and for the
      dimerization of monomeric acid in carbon tetrachloride (deltaH and deltaS) were
      evaluated from the van't Hoff isochore. The free-energy change for the transfer
      of a methylene group from water to organic solvents was entropically controlled,
      irrespective of the organic solvents. The distribution constants of formic and
      benzoic acids were larger than those expected from the distribution constants of
      acetic and phenylacetic acids, respectively. The free-energy change for all
      solutes, except for benzoic and 4-methylbenzoic acids, was also entirely
      entropically controlled in the case of octanol as a solvent. The enthaly-entropy
      compensation for the dimerization constant of acids in carbon tetrachloride was
      observed.

PMID- 11990621
TI  - Extraction separation and electrothermal atomic absorption spectrometric
      determination of thallium in some sulfide minerals.
AB  - A method for thallium determination in some sulfide minerals (sphalerite, galena,
      orpiment and realgar) by electrothermal atomic absorption spectrometry has been
      proposed. Mineral samples were dissolved in a mixture of HNO3 and HCl. The effect
      of interfering elements (Zn, Pb and As) on the determination of Tl in the
      investigated minerals was studied. These investigations show that it is not
      possible to determine thallium directly from solutions obtained by dissolution of
      minerals in mineral acids, because these matrix elements tend to decrease the
      absorbance of thallium. Also, it was found that the investigated minerals contain
      iron that tends to increase the absorbance of thallium. Therefore, a method for
      extraction of thallium with isoamyl acetate from 10 mol/l HCl media was proposed.
      In these conditions, Zn, Pb and As remain in the inorganic phase, but iron and
      thallium are extracted into organic phase. Reextraction of iron from the organic
      layer was performed with 4 mol/l H2SO4. The determination of thallium was
      performed in the organic phase using Pd as modifier. The investigated sulfide
      minerals originated from different mines from the Republic of Macedonia. The
      relative standard-deviation range was between 2.20 to 3.92%. The detection limit
      of the method (calculated as 3SD of the blank) was found to be 0.05 microg/g.

PMID- 11990622
TI  - Application of an HPLC-FTIR modified thermospray interface for analysis of dye
      samples.
AB  - Previously, we developed a reversed-phase HPLC method compatible to high
      performance liquid chromatography diffuse reflectance Fourier-transform infrared
      (HPLC-FTIR) thermospray interface for the analysis of dyes. Dye separation
      achieved with a mixed-mode (SCX-ODS) column using a small gradient (90 to 80%
      water with acetic acid) and pH 3.25; 10 to 20% acetonitrile was considered to be
      suitable for HPLC-FTIR. A constant-voltage setting for the thermospray
      temperature (227 degrees C) was successfully used for this gradient condition.
      The HPLC-separated components deposited as a series of concentrated spots on a
      moving tape were scanned by specially developed HPLC-FTIR software. Excellent
      repeatability of the thermospray deposition FTIR chromatograms and IR spectra was
      obtained. The interface-derived spectra of the separated components of formulated
      and purified reactive dyes were compared and differences in spectral features
      were observed.

PMID- 11990623
TI  - Kinetic spectrophotometric determination of thiocyanate based on its inhibitory
      effect on the oxidation of methyl red by bromate.
AB  - A kinetic spectrophotometric method for measuring thiocyanate is described. The
      proposed method is based on the inhibitory effect of thiocyanate on the oxidation
      of Methyl Red by bromate in the presence of nitrite, which was monitored at 520
      nm. The variables affecting the rate of the reaction were investigated and the
      optimum conditions were established. Thiocyanate can be measured in the range of
      0.05-1.1 microg ml(-1) with a detection limit of 0.025 microg ml(-1). This method
      has been used to determine trace thiocyanate in urine and tap water samples.

PMID- 11990624
TI  - Dapsone and iminodibenzyl as novel reagents for the spectrophotometric
      determination of trace amounts of nitrite in water samples.
AB  - A rapid, simple, sensitive and selective spectrophotometric determination of
      nitrite using new diazotizing and coupling reagents is described. The method is
      based on a diazotization-coupling reaction between dapsone and iminodibenzyl in a
      hydrochloric acid medium. The molar absorptivity and Sandell's sensitivity were
      found to be 7.5 x 10(4) l mol(-1) cm(-1) and 0.000613 microg ml(-1),
      respectively. The interference effects of various cations and anions were also
      studied and reported. This method has been found to be applicable for the
      determination of nitrite in various water samples.

PMID- 11990625
TI  - Univariate and simplex optimization for the flow-injection spectrophotometric
      determination of copper using nitroso-R salt as a complexing agent.
AB  - A simple colorimetric flow-injection system for the determination of Cu(II) based
      on a complexation reaction with nitroso-R salt is described. The chemical and FIA
      variables were established using the univariate and simplex methods. A small
      volume of Cu(II) was mixed with merged streams of nitroso-R salt and acetate
      buffer solutions. The absorbance of the complex was continuously monitored at 492
      nm. The calibration curve over the concentration range 1.0-7.0 microg ml(-1) was
      obtained. The relative standard deviation for determining 4.0 microg ml(-1)
      Cu(II) was 0.47% (n = 11). The detection limit (3sigma) was 0.68 microg ml(-1)
      and the sample throughput was 150 h(-1). The validity of the method has been
      satisfactorily examined for the determination of Cu(II) in wastewater and copper
      ore samples. The accuracy was found to be high, because the student t-values were
      calculated to be less than the theoretical values when the results were compared
      with those obtained by FAAS.

PMID- 11990626
TI  - Incident-angle dependence of the sensitivity of second-harmonic generation of an
      oxacyanine dye in an LB film.
AB  - The second-harmonic generation of a cyanine dye in an LB film was investigated by
      varying the incident angle of the excitation laser. There was a clear dependence
      on the incident angle, which was simulated by a simple model. Thus, a highly
      sensitive determination should be carried out at such an angle where the
      efficiency of the second-harmonic generation shows its maximum.

PMID- 11990627
TI  - Negative-ion FAB-MS of neutral tris- and bis(L-alpha-amino acidato)-chromium(III)
      complexes.

PMID- 11990628
TI  - On-line preconcentration system using a packed-bed filter for the determination
      of lead in tap water by inductively coupled plasma atomic emission spectrometry
      with ultrasonic nebulization.

PMID- 11990630
TI  - Crystal structure of 3,4,6,7,15,16,17,18,19,20,21,27-dodecahydro-2,5,8-trioxa
      16,20-diazatetracyclo[20.4.1.(16,20)0.0(9,14)]heptacosa-9,11,13,22,24,26(1)
      hexaene.

PMID- 11990629
TI  - Coprecipitation of trace metal ions in water with bismuth(III)
      diethyldithiocarbamate for an electrothermal atomic absorption spectrometric
      determination.

PMID- 11990631
TI  - Crystal structure of an antidiabetic agent, (+/-)-5-[4-(6-hydroxy-2,5,7,8
      tetramethylchroman-2-ylmethoxy)benzyl]-2,4-dioxothiazollidine, troglitazone
      dihydrate.

PMID- 11990632
TI  - Crystal structure of trans-(dicyano)bis(triphenylphosphine)palladium(II)
      dichloromethane solvate.

PMID- 11990633
TI  - Crystal structure of tris(((5-bromosalicylidene)amino)ethyl)amine.

PMID- 11990634
TI  - Crystal structure of a samarium(III) complex of tripodal tris(((5
      chlorosalicylidene)amino)ethyl)amine.

PMID- 11990635
TI  - U.S. agencies providing publicly funded contraceptive services in 1999.
AB  - CONTEXT: Nearly one-quarter of women who obtain medical contraceptive services
      receive care from clinics operated by publicly funded agencies. In light of
      changes in government policy and funding and in the structure of health care
      financing, an assessment of agency policies and programs is essential for
      monitoring women's access to contraceptive care and services. METHODS: In 1999,
      637 of a nationally representative sample of 1,016 U.S. agencies that receive
      public funding to provide contraceptive services responded to a 12-page survey.
      Responses were analyzed according to agency type, receipt of Title X funding and
      main focus. RESULTS: More than nine in 10 agencies offer the pill, the male
      condom and the injectable; 80% offer emergency contraceptive pills, compared with
      38% in 1995. Some agencies allow clients to delay a pelvic exam when beginning
      use of oral contraceptives (56%), the injectable (42%) or the implant (23%). On
      average, agencies receive funding for contraceptive services from 4.9 sources;
      the proportion relying on private insurance and contributions has risen since
      1995. Virtually all family planning agencies provide screening and testing for
      sexually transmitted diseases (STDs), and at least two-thirds offer treatment for
      most STDs. The vast majority of agencies offer general health care and perinatal
      or pediatric services; half offer general gynecologic care or infertility
      services. Services provided, costs and clinic policies vary according to agency
      type. CONCLUSIONS: Agencies offering contraceptive services also offer a wide
      range of reproductive health and related services. There remain services for
      which provision could be increased and policies that need to be modified to
      facilitate clients' access to contraceptive care.

PMID- 11990636
TI  - Did abortion legalization reduce the number of unwanted children? Evidence from
      adoptions.
AB  - CONTEXT: The legalization of abortion in the United States led to well-known
      changes in reproductive behavior, but its effect on adoptions has not been
      investigated. METHODS: Variation across states in the timing and extent of
      abortion legalization is used to identify the effects of changes in the legal
      status of abortion on adoption rates from 1961 to 1975. These effects are
      estimated in regression analyses that control for states' economic, demographic
      and political characteristics, as well as for health care availability within
      states. RESULTS: The rate of adoptions of children born to white women declined
      by 34-37% in states that repealed restrictive abortion laws before Roe v. Wade.
      The effect was concentrated among adoptions by petitioners not related to the
      child. Legal reforms resulting in small increases in access, such as in cases of
      rape and incest, were associated with a 15-18% decline in adoptions of children
      born to nonwhite women; however, this decline may have been due to other changes
      in the policy environment for such adoptions. Rates of adoption of children born
      to white women appear to have declined after Roe v. Wade, but this association is
      not statistically significant. CONCLUSIONS: The estimated effect of abortion
      legalization on adoption rates is sizable and can account for much of the decline
      in adoptions, particularly of children born to white women, during the early
      1970s. These findings support previous studies' conclusions that abortion
      legalization led to a reduction in the number of "unwanted" children; such a
      reduction may have improved average infant health and children's living
      conditions.

PMID- 11990637
TI  - Having an abortion using mifepristone and home misoprostol: a qualitative
      analysis of women's experiences.
AB  - CONTEXT: Women choose medical over surgical abortion because it is more natural,
      more private and less painful. Whether their perceptions change during the
      medical abortion process has not been explored. METHODS: A nonprobabilitysample
      of 43 participants in a clinical trial of abortion using mifepristone completed
      two open-ended questionnaires about this method, one before taking mifepristone
      and the second during their follow-up clinic visit 4-8 days after taking
      misoprostol. Thirty women participated in in-depth interviews 1-6 weeks following
      their abortion. Researchers analyzed transcripts to identify common themes.
      RESULTS: On the first visit to the clinic, women expressed anxiety and
      uncertainty about the effectiveness of medical abortion, guilt or ambivalence,
      and a desire to avoid surgery. For most women, emotional distress decreased after
      their abortion. Control was the overarching theme women expressed regarding the
      meaning of the procedure: Women stressed the importance of being able to select
      the type of abortion procedure, to maintain control over their future and to
      preserve their family's quality of life, given the constraints of time, finances
      and emotional resources. In in-depth interviews, eight women remained concerned
      about long-term health effects; 18 said that having an abortion at home was a
      comfortable experience. CONCLUSIONS: Learning whether women are concerned about
      personal control may help clinicians identify appropriate candidates for medical
      abortion. In addition, clinicians could help allay women's anxiety at their first
      abortion visit by explaining that the uncertainties posed by any medical
      procedure create similar feelings. Clinicians also should reemphasize at the
      follow-up visit that there are no long-term health effects related to abortion.

PMID- 11990638
TI  - Early childbearing and children's achievement and behavior over time.
AB  - CONTEXT: Compared with children of older women, children of women who had their
      first birth during their teens have long been believed to be at higher risk for a
      host of poor health, social and economic outcomes. Recent studies have failed to
      confirm this belief, but none have taken into account whether children's outcomes
      or the effects of early childbearing on those outcomes have changed over time.
      METHODS: Data from the National Longitudinal Survey of the Labor Market
      Experience of Youth and the Panel Study of Income Dynamics are used to separate
      the influence of changes from the 1960s through the 1990s in children's
      experiences from the effect of mother's age at first birth. RESULTS: Multivariate
      analyses controlling for social and demographic characteristics show that among
      children born to women from a particular birth cohort, those whose mothers first
      gave birth in their teens have significantly lower scores on a set of four
      achievement tests and significantly higher scores on a behavior-problem index
      than do children whose mothers delayed childbearing. However, when changes over
      time in children's outcomes and in the effect of early childbearing on those
      outcomes are taken into account, children born to women who began childbearing
      early score significantly worse than those whose mothers delayed their first
      birth on the behavior-problem index, but on only one achievement test.
      CONCLUSIONS: Comparisons by age at first birth among women born in the same
      period may misestimate the effects of early motherhood. Whether early
      childbearing's effects on children are overestimated or underestimated depends on
      whether test scores are rising or falling. Policymakers should be cautious in
      making decisions based on studies that do not take time trends into account.

PMID- 11990639
TI  - The trade-off between hormonal contraceptives and condoms among adolescents.
AB  - CONTEXT: Adolescents' dual use of condoms and hormonal contraceptives is low, and
      the motivations underlying their decisions to combine contraceptives are not
      understood. METHODS: To examine how pregnancy concerns, sexually transmitted
      disease (STD) concerns and type of sexual partner influence contraceptive use, we
      recruited 436 sexually experienced adolescents from two clinics. In structured
      interviews, we asked adolescents to describe their recent partners, their method
      use, and their pregnancy and STD concerns. Data were analyzed using logistic
      regression. RESULTS: The odds that adolescents used condoms with main partners
      were significantly lower among those who used hormonal contraceptives than among
      nonusers of these methods (odds ratios, 0.4 for young women and 0.3 for young
      men). With casual partners, no association existed between adolescents' condom
      and hormonal contraceptive use. Concerns about pregnancy and STDs influenced this
      association for women with main partners. Among young women who perceived
      pregnancy as more negative, hormonal contraceptive users had reduced odds of
      using condoms (0.1). No association existed between use of the two methods among
      young women whose view of pregnancy was less negative. Young women who perceived
      themselves to be less at risk of acquiring an STD had reduced odds of using
      condoms if they were using hormonal contraceptives (0.2). Among young women who
      perceived themselves to be more at risk of acquiring an STD, no association
      existed. CONCLUSIONS: Adolescents trade off between hormonal contraceptives and
      condoms according to partner type and perceived risks. Adolescents' dual-method
      use may improve if providers tailor counseling to adolescents' perceived risk of
      STDs and pregnancy, and if they address prevention of both as a related decision.

PMID- 11990640
TI  - Halting the progression of heart failure: finding the optimal combination
      therapy.
AB  - Finding the optimal combination of drugs in the correct dosages, which requires
      careful monitoring over time, is key to slowing the disease process and
      prolonging life. For most patients, treating heart failure involves correcting
      underlying left ventricular dysfunction, thereby slowing the remodeling process.

PMID- 11990641
TI  - A primer on referring patients for psychotherapy.
AB  - Forty percent of the mental health care in this country is provided by primary
      care practitioners alone, and another 20% is provided by primary care
      practitioners working with mental health professionals. Primary care physicians
      can serve a valuable role by educating their patients about various forms of
      psychotherapy. Finding a good "fit" between patient and therapist is crucial to a
      good outcome. We discuss which psychotherapeutic techniques are appropriate for
      various emotional problems and the advantages and disadvantages of each.

PMID- 11990642
TI  - A 23-year-old man with a continuous heart murmur.

PMID- 11990643
TI  - Diagnosis of lupus: a glass half full.

PMID- 11990644
TI  - Tired, aching, ANA-positive: does your patient have lupus or fibromyalgia?
AB  - The symptoms of fibromyalgia and lupus can be similar, but the treatments are
      very different. Although the antinuclear antibody (ANA) test has often been used
      to make the distinction, this approach has its pitfalls. This paper offers
      strategies for more accurate diagnosis.

PMID- 11990645
TI  - What is the best way to diagnose streptococcal pharyngitis?

PMID- 11990646
TI  - Advances in treatment of chronic hepatitis C: 'pegylated' interferons.
AB  - New regimens consisting of pegylated interferons plus ribavirin may produce a
      sustained virologic response in more than 50% of cases of chronic hepatitis C. In
      contrast, the combination of standard interferon alfa and ribavirin, which was
      the standard of care until recently, produced a sustained virologic response in
      35% to 40% of cases. As the efficacy of newer regimens improves, additional steps
      to adequately manage their side effects and maximize adherence may become
      crucial.

PMID- 11990647
TI  - Idiopathic retroperitoneal fibrosis: prompt diagnosis preserves organ function.
AB  - Prompt diagnosis of idiopathic retroperitoneal fibrosis improves chances of
      preserving renal function, preventing involvement of other organs, and relieving
      symptoms. Computed tomography or magnetic resonance imaging helps to exclude
      secondary causes, but open biopsy remains the gold standard for diagnosis.
      Management typically includes surgery (ureterolysis, stent placement), and drug
      treatment (corticosteroids), or a combination of both. However, no surgical or
      medical therapy has been tested in a randomized, controlled trial.

PMID- 11990648
TI  - Chronic tension-type headache: advice for the viselike-headache patient.
AB  - About 3% of people experience daily viselike headaches without other associated
      symptoms, a condition called chronic tension-type headache. Therapy consists of
      tricyclic antidepressants, biofeedback, and stress management, although
      compelling data from randomized controlled trials are lacking.

PMID- 11990649
TI  - Patient information. Taking the tension out of tension-type headaches.

PMID- 11990650
TI  - How we do it: pancreatic cancer staging.

PMID- 11990651
TI  - Optimal imaging of the sacrum: the role of spiral CT and 3D CT imaging--a
      pictorial review.

PMID- 11990652
TI  - Case of the month. Pseudomembranous colitis.

PMID- 11990653
TI  - Thoracic calcifications in childhood.
AB  - Thoracic calcifications are found in the following locations: mediastinum, lung,
      pleura, cardiovascular system, and thoracic wall. The calcifications of the
      mediastinum include mostly inflammatory lesions and malignant neoplasms.
      Pulmonary calcifications are mainly inflammatory lesions and metastases of
      osteosarcomas. Where the cardiovascular system is concerned, the most common
      calcifications are those of the heart relating to tumors or surgery.
      Calcifications of the aortic wall and valve calcifications can be found. In the
      thoracic wall there are calcifications of the bone and of soft tissues. The
      knowledge of shape and location is very useful for the diagnosis of the
      underlying disease. Calcifications in the thorax are frequently manifestations of
      previous infectious processes. Less often, they may be due to neoplasms,
      metabolic disorders, or previous medical therapy.

PMID- 11990654
TI  - The unnecessary pacemaker controversy revisited.

PMID- 11990655
TI  - Criteria for pacemaker explant in patients without a precise indication for
      pacemaker implantation.
AB  - Unnecessary pacemaker implantation may cause significant social and psychological
      consequences, the inconvenience of periodic office visits, and the expense of
      pulse generator replacement. Establishing adequate criteria for
      explantingpacemakers is crucial and has notyet been described. This study
      presents the results of a study protocol for explanting the pacemaker in patients
      without a clear indication for pacemaker implantation. Seventy pacemaker users
      without a clear reason for the implantation were included in the study conducted
      from August 1986 to November 1998 and were prospectively followed. The
      investigation consisted of clinical and neurological evaluations, echocardiogram,
      exercise testing, and tilt table testing. When these tests were negative, the
      pulse generator energy and stimulation rates were reprogrammed to the lowest
      values. Periodic Holter monitoring was conducted during follow-up. When
      asymptomatic for 1 year, patients underwent an electrophysiological evaluation of
      sinus and atrioventricular junction function and ventricular vulnerability. When
      the electrophysiological study was negative, pacemaker explantation was
      performed. Of the 70 patients, 35 had their pacemaker explanted; 3 were excluded
      due to a positive tilt table test and electrophysiological study, and 3 are
      waitingfor pacemaker explantation. Mean follow-up after pacemaker explantation
      was 30.3 months, and all patients remained asymptomatic, exceptfor one patient
      who died of a noncardiac cause. Critical analysis of pacemaker users without a
      well-established indication is justified because it may allowpacemaker explant in
      a significant proportion of these patients, and it may bring considerable social,
      economic, and psychological benefits.

PMID- 11990656
TI  - Reversion and maintenance of sinus rhythm in patients with permanent atrial
      fibrillation by internal cardioversion followed by biatrial pacing.
AB  - Patients in atrialfibrillation (AF) who fail external cardioversion are usually
      regarded as in permanent AF. Internal cardioversion may revert many such patients
      into sinus rhythm (SR) but the majority relapse rapidly into AF. We investigated
      whether internal cardioversion followed by biatrial pacing is an effective to
      restore and subsequently maintain SR in patients with permanent AF. Patients in
      permanent AF underwent internal cardioversion that was followed by biatrial
      temporary pacing for 48 hours. Those who remained in SR received a permanent
      biatrial pacemaker programmed to a rate responsive mode with a lower rate 90
      beats/min. Primary end point of the study included maintenance in SR 3 months
      after internal cardioversion. Sixteen patients (14 men, 57 +/- 11 years) were
      cardioverted. The median duration of AF was 24 months (quartiles, Q1 = 8.5 and Q3
      = 102) and mean left atrium diameter was 48 +/- 04 mm. A permanent biatrial
      pacemaker was implanted in 11 patients. At a mean fallow-up of 15 months (range 4
      to 24), 8 patients remained in SR for more than 3 months. AF was eliminated in 5
      patients, while in two a second internal cardioversion on amiodarone was
      required. Antiarrhythmic therapy was used in half of our population and did not
      predict the long-term maintenance of SR. Following internal cardioversion with
      continuous biatrial pacing, 50% of patients with permanent AF were maintained for
      prolonged periods in SR. This is a new modality of treatment of permanent AF
      directed to the maintenance of SR that provides a further therapeutic option in
      end-stage AF.

PMID- 11990657
TI  - Rapid pacing results in changes in atrial but not in ventricular refractoriness.
AB  - It is well known that atrial tachycardia causes atrial electrical remodeling,
      characterized by shortening of atrial effective refractory periods (AERPs) and
      loss of physiological adaptation of AERP to rate. However, the nature and time
      course of changes in ventricular effective refractory periods (VERP) caused by
      rapid rates are to be established. After being instrumented with epicardial
      electrodes on both atria and both ventricles nine goats were subjected to 1 week
      of rapid AV pacing with a rate of 240 beats/min and an AV delay of 100 ms. Pacing
      was only interrupted for measurement of left and right AERPs and VERPs at three
      basic cycle lengths (BCL) of 400 ms, 300 ms, and 200 ms during sinus rhythm in
      the conscious animal. Left and right AERPs decreased at all BCLs, reaching
      minimum values after 3 days (right AERP at BCL of 400 ms, 96 +/- 16 ms after 3
      days vs 144 +/- 16 ms at baseline, P < 0.05). In contrast, both left and right
      VERPs did not change at any BCL. This study demonstrates a difference between the
      atria and ventricles with respect to tachycardia induced changes in
      refractoriness.

PMID- 11990658
TI  - Transient proarrhythmic state following atrioventricular junctional
      radiofrequency ablation.
AB  - This study was designed to prospectively assess ventricular de- and
      repolarization by the QRS, QT, and JT intervals, and their dispersion in the 12
      lead ECG during right ventricular pacing at 60, 70, and 80 beats/min during the
      first month after AV junctional RF ablation. Previous reports have found early
      polymorphic ventricular arrhythmia after RF AV junctional ablation. Our
      hypothesis was that there is a proarrhythmic state following this procedure,
      which depends on the paced rate and time after ablation. The analysis of the
      immediate changes was based on 17 patients (10 men) with a mean age of 64 years
      (SD 14) (range 38-82 years). A 12-lead ECG was recorded during right ventricular
      pacing at 60, 70, and 80 beats/min within 24 hours (day 1), between 24 and 48
      hours (day 2), and 1 week after ablation (day 7). For analysis of changes beyond
      1 week, 13 additional patients with a mean age of 73 years (SD 8) (range 62-90
      years) were analyzed on days 1, 7, and 30. All intervals were measured with a
      digitizing table. The mean QRS duration shortened by 2.4% at 60 beats/min (P
      <0.01), and the mean QT and JT intervals shortened by 5-7% between days 1 and 7
      (P < 0.001). The mean QT was 9% shorter and the mean JT interval was 13% shorter
      at 80 compared to 60 beats/min on day 1 (P < 0.001). QT dispersion was reduced by
      13% when the stimulation rate was increasedfrom 60 to 80 beats/min on day 1 (P <
      0.05). There were no significant changes beyond the first week. The study results
      point to the induction of a proarrhythmic state immediately after AV junctional
      RF ablation resolving during the first week. Repolarization shortened gradually
      between 80 and 60 beats/min to an extent that is suggestive of a clinically
      important antiarrhythmic effect at the higher rate, which was supported also by
      clinical experience.

PMID- 11990659
TI  - Detection of rapid changes in ventricular refractoriness in human studies.
AB  - Conventional determination of the ventricular effective refractory period (VERP)
      is unsuitable for detection of rapid fluctuations in the effective refractory
      period (ERP). A programmed stimulation system was developed that adapts
      continuous atrioventricular sequential pacing, incremental extrastimulus interval
      (S1S2) scanning, and automatic detection of extrastimulus capture which is
      followed by shortening of S1S2 to execute repeated scanning. The accuracy of ERP
      determination was tested using variable incremental (2 and 4 ms) and decremental
      (4-16 ms) steps of the S1S2 interval. Based on a mean of 82 determinations in
      eight patients, the average VERP values stayed at 249.8-251.0 ms except during
      the highest capture frequency. Standard deviation of ERP values ranged from 1.1
      to 2.5 ms on average at the tested incremental and decremental steps. One
      determination was accomplished within 7.8-15.6 seconds on average. The ability to
      track changes in ERP was tested by changing the drive cycle length. Time
      constants for the adaptation rate of VERP and ventricular monophasic action
      potential duration at a 90% level of repolarization were determined from each
      test, and were similar, 51 +/- 8 seconds (mean +/- SEM) for ERP and 51 +/- 6
      seconds for the action potential duration. Thus, the developed method provides
      accurate ERP measurements during rapid variation in ventricular refractoriness.
      It allows studying the recovery of excitability and the action potential duration
      simultaneously, and would be valuable particularly in pathological conditions and
      pharmacologic interventions where these electrophysiological variables become
      dissociated.

PMID- 11990660
TI  - Progressive isthmus delay during atrial flutter ablation: the critical importance
      of isthmus spanning electrodes for distinguishing pseudoblock from block.
AB  - Bidirectional isthmus block is associated with successful atrial flutter
      ablation, whereas creation of increased isthmus conduction delay without block
      can be proarrhythmic. Often, halo catheter electrodes fail to provide adequate
      sub-Eustachian isthmus recordings. The aim of this study was to determine if
      progressive isthmus conduction delay results in the false appearance of block
      during atrialflutter ablation. A 20-pole deflectable catheter was prospectively
      positioned across the sub-Eustachian isthmus (from the coronary sinus os [CSO] to
      7:00 on the tricuspid valve annulus [TVA] clock face in the left anterior oblique
      [LAO] projection) in nine patients undergoing atrial flutter ablation. During
      sinus rhythm, conduction time was measured from the CSO to the 7:00 position
      while pacing the CSO. Measurements were repeated after each linear lesion and
      after conduction block was achieved. Transisthmus conduction time at baseline,
      just prior to success, and after the presence of complete block was 54 +/- 9, 123
      +/- 39, and 155 +/- 30 ms, respectively (P < or = 0.01). The marked delay prior
      to complete block resulted in reversal of the activation sequence in electrodes
      at TVA 7:00, creating the false appearance of isthmus block; the isthmus
      electrodes clearly distinguished delay from block. Catheter ablation results in
      progressive isthmus conduction delay prior to the creation of complete block.
      Electrodes spanning the isthmus and line of block are critical for distinguishing
      conduction delay (and pseudoisthmus block) from block.

PMID- 11990661
TI  - Implantation strategy of the atrial dipole impacts atrial sensing performance of
      single lead VDD pacemakers.
AB  - Intermittent atrial undersensing is observed in a considerable percentage of
      patients with single lead VDD pacemakers. Analyzing the 2-year data of the Saphir
      Multicenter Follow-Up Study, the authors investigated predictors for the
      occurrence of undersensing. The study included 194 patients with high degree AV
      block who received a VDD pacemaker system with an identical sensing amplifier.
      Placement strategy of the atrial dipole was left to the discretion of the
      implanting physician. At the final position, atrial potential amplitudes were
      measured during deep and shallow respiration. Atrial dipole position was
      determined by intraoperativefluoroscopy subdividing the right atrium in a high,
      mid, and low portion. Undersensing was defined by evidence of at least one not
      sensed P wave during Holter monitoring or exercise testing and by the presence of
      0.1-0.2 mV amplitudes in the P wave amplitude histogram of the pacemaker.
      Incidence of undersensing was 25.8%; 9.3% of patients showed frequent (> 5%) or
      symptomatic undersensing. Patients with undersensing were older (76.6 +/- 10.6 vs
      64.2 +/- 14.8 years), showed a lower minimum of intraoperative atrial potential
      amplitude (P(min) 0.86 +/- 0.64 vs 1.43 +/- 0.77 mV), a wider range of potential
      amplitude (deltaP 1.71 +/- 1.44 vs 0.94 +/- 0.84 mV), and a higher incidence of
      dipole placement in the low right atrium (50.0% vs 11.1 %, P < 0.001 for all
      comparisons). In a multivariate regression analysis, patient age > 66 years, Pmin
      < 0.6 mV, > 1.3 mV and atrial dipol placement in the lowright atrium were
      independently predictive for undersensing. Minimal atrialpotential amplitude,
      range of potential amplitude, and atrial dipole position influence atrial sensing
      performance in single lead VDD pacing. Thus, implantation guidelines should
      reflect these rules to improve the outcome of VDD pacemaker recipients.

PMID- 11990662
TI  - Human experience with transvenous biventricular defibrillation using an electrode
      in a left ventricular vein.
AB  - This study investigated the safety and feasibility of transvenous biventricular
      defibrillation in ICD patients. Some patients may have high DFTs due to weak
      shock field intensity on the LV. Animal studies showed a LV shocking electrode
      dramatically lowered DFTs. This approach might benefit heart failure patients
      already receiving a LV lead or conventional ICD patients with high DFTs. A
      modified guidewire was used as a temporary left venous access defibrillation
      electrode (LVA lead). In 24 patients receiving an ICD, the LVA lead was advanced
      through a guide catheter in the coronary sinus (CS) and into a randomized LV vein
      (anterior or posterior) using a venogram for guidance. Paired DFT testing
      compared a standard right ventricular defibrillation system to a biventricular
      defibrillation system. There were no complications or adverse events. As
      randomized, LVA lead insertion success was 87% and 71% for anterior and posterior
      veins, respectively, and 100% after crossover. Total insertion process time
      included venogram time (32.5 +/- 26.9 minutes, range 5-115, mode 15 minutes) and
      LVA lead insertion time (15 +/- 14 minutes, range 1-51, mode 7 minutes). An
      apical LVA lead position was achieved in 11 (45%) of 24 patients and 7 (64 %) of
      these 11 displayed a DFT reduction; however, mean DFTs were not statistically
      different. Transvenous biventricular defibrillation is feasible and was safe
      under the conditions tested. Additional clinical studies are justified to
      determine if optimized LV lead designs, lead placement, and shock configurations
      can yield the same large DFT reductions as observed in animals.

PMID- 11990663
TI  - Prospective assessment after pediatric cardiac ablation: design and
      implementation of the multicenter study.
AB  - A multicenter prospective study was designed and implemented as an activity of
      the Pediatric Electrophysiology Society to assess the risks associated with
      radiofrequency ablation in children. Patients (age 0-15 years) with
      supraventricular tachycardia due to accessory pathways or atrioventricular nodal
      reentry were enrolled and studied prior to ablation and periodically by clinical
      evaluation, electrocardiogram (ECG), Holter monitor, and echocardiogram. In
      addition, a national registry was established, to which the contributing centers
      report all pediatric patients undergoing ablation at their center. Initial
      electrophysiological study tracings and all noninvasive studies undergo blinded
      outside review for quality control. Clinical endpoints were death, recurrence,
      proarrhythmia, and echocardiographic abnormality. A pilot study demonstrated
      excellent agreement concerning diagnoses of previously reported ablation patients
      between the reporting center and the blinded reviewer (kappa = 0.938 +/- 0.062).
      A total of 317 patients were enrolled in the ongoing study from April 1, 1999 to
      December 31, 2000. The success rate of ablations was 96% with a complication rate
      of 4.3% for electrophysiological study and 2.9% for the ablation procedure.
      Comparison of the registry group versus the study group shows that the groups are
      comparable in terms of patient characteristics, diagnoses, and the results of
      ablation making it less likely that the sample of prospectively enrolled patients
      is biased.

PMID- 11990664
TI  - Gross structure of the atriums: more than an anatomic curiosity?
AB  - Despite the extensive literature concerning atrial arrhythmias, there are
      relatively few articles on the anatomy of the atrial chambers. Since
      electrophysiological mapping and interventional treatments of atrial arrhythmias
      involve entering the chambers, this article reviews the gross structures to
      provide a better understanding of the atriums, the septum, and the connecting
      great veins. In addition, based on the human heart, differences between porcine
      and canine hearts are highlighted. The right and left atriums are characterized
      by morphologically distinct appendages. The right atrium contains prominent
      muscular bundles and an extensive array of pectinate muscles. The distal
      ramifications of the terminal crest lead to the "flutter" isthmus. By contrast,
      the left atrium has relatively smooth walls. The atrial septum is limited to the
      valve of the oval fossa and its immediate muscular rim. Atrial musculature
      extends beyond the veno-atrial junctions to the outside of the pulmonary veins.
      The longest sleeves are around the upper pulmonary veins, and similar sleeves are
      seen around the superior caval vein. The structure of the atrium is more than an
      anatomic curiosity. It has practical implicationsfor mapping and interventional
      procedures.

PMID- 11990665
TI  - Feasibility study of real-time three-dimensional intracardiac echocardiography
      for guidance of interventional electrophysiology.
AB  - The authors tested the feasibility of real-time three-dimensional intracardiac
      echocardiography for guidance of interventional electrophysiological studies. The
      three-dimensional scanner uses a matrix array ultrasound transducer of 64
      channels operating at 5 MHz in a 12 Fr catheter. The system features real-time
      three-dimensional image rendering and produces up to 60 volumetric scans per
      second. Using an open-chest sheep model, real-time three-dimensional images of
      anatomic landmarks were obtained, including the pulmonary veins and coronary
      sinus, which are of value in electrophysiological procedures. In vivo radio
      frequency ablation procedures in the right ventricle were also monitored, which
      yielded lesions of high image contrast.

PMID- 11990666
TI  - Just another case of atrial fibrillation?

PMID- 11990667
TI  - Signal-averaged electrocardiographic parameter progression as a marker of
      increased electrical instability in two cases with an overt form of
      arrhythmogenic right ventricular cardiomyopathy.
AB  - In arrhythmogenic right ventricular cardiomyopathy (ARVC) the fibrofatty
      substitution of the RV myocardium constitutes the substrate for reentrant
      circuits, leading to the onset of ventricular arrhythmias. This pathological
      process also accounts for "delayed ventricular potentials" that could be recorded
      as late potentials using the signal-averaged ECG technique (SAECG). This study
      examined two patients affected by overt forms of ARVC who showed a worsening of
      the electrical instability associated with a fast progression of SAECG
      parameters, while all the other clinical findings remained unchanged. This
      suggests a possible role of SAECG parameter progression as a marker of increased
      electrical instability.

PMID- 11990668
TI  - Inhibition of biventricular pacemakers by oversensing of far-field atrial
      depolarization.
AB  - This report describes two patients who exhibited far-field oversensing of the P
      wave by the ventricular channel of a DDD biventricular pacemaker implanted for
      the treatment of congestive heart failure. Oversensing probably occurred
      secondary to slight displacement of the left ventricular lead in the coronary
      venous system. Long-term reliable pacing was restored by decreasing the
      sensitivity of the ventricular channel.

PMID- 11990669
TI  - Radiofrequency ablation of sustained ventricular tachycardia related to the
      mitral isthmus in Chagas' disease.
AB  - This case report describes the electrophysiological findings of a 62-year-old
      patient with chronic Chagas' disease and two distinct morphologies of sustained
      ventricular tachycardia that involved a mitral isthmus. Multiple RF applications
      were necessary to obtain a bidirectional conduction block in the mitral isthmus
      that was related to the interruption of both tachycardias. After the procedure,
      the patient presented massive cerebral infarction that progressed to coma and
      death. Autopsy showed acute and old lesions at the mitral isthmus and recent
      mitral annulus thrombosis.

PMID- 11990670
TI  - Cerebral syncope in a patient with spinal cord injury.
AB  - An 80-year-old patient suffering from traumatic paraplegia due to spinal cord
      compression was admitted due to recurrent orthostatic syncope. Tilt table testing
      revealed that the patient lost consciousness without hypotension. Doppler flow
      measurements of the middle cerebral arteries showed a significant decrease in
      diastolic velocity during syncope without systemic hypotension. Treatment with
      beta-blockers was highly effective. The patient suffered from cerebral blood flow
      disregulation probably due to abnormal baroreceptor responses triggered during
      orthostatic stress. This is the first reported case of a patient with spinal cord
      injury suffering from such an unusual cause of syncope.

PMID- 11990671
TI  - Successful radiofrequency current catheter ablation of accessory atrioventricular
      pathway in Ebstein's anomaly using electroanatomic mapping.
AB  - Ebstein's anomaly is highly associated with atrioventricular reciprocating
      tachycardia (AVRT) due to an atrioventricular accessory pathway (AP). This case
      report describes a case of a 30-year-old man with Ebstein's anomaly who had been
      suffering from recurrent palpitation caused by AVRT due to the right-sided AP.
      Conventional mapping technique failed to ablate his AP successfully. In baseline
      electrophysiological study, orthodromic AVRT with a right posterior AP were
      induced. The AP was mapped using an electroanatomic mapping system. RF current
      was successfully delivered at the posterior site. RFCA using an electroanatomic
      mapping system seems to be useful for A VRT patients in Ebstein's anomaly.

PMID- 11990672
TI  - Constrictive pericarditis complicating endovascular pacemaker implantation.
AB  - A patient is described who has 6 months of progressive dyspnea and peripheral
      edema for 4 years following implantation of an endovascular pacemaker, which was
      complicated by a large hemorrhagic pericardial effusion. Evaluation was
      consistent with constrictive pericarditis, which is an extremely unusual
      complication of pacemaker implantation.

PMID- 11990673
TI  - Pacemaker pocket infection due to acremonium species.
AB  - Fungal infections involving the pacemaker pocket after pacemaker implantation
      procedure are extremely rare. This report describes the case of a 53-year-old
      woman with pacemaker pocket infection due to acremonium species. The authors
      emphasize that this patient did not have any predisposing factors to fungal
      infections.

PMID- 11990674
TI  - Analysis of mode switching algorithms in dual chamber pacemakers.
AB  - Dual chamber systems are currently implanted in an increasing number of patients
      with a pacing indication and paroxysmal atrial tachyarrhythmias (ATAs). To avoid
      tracking of high atrial rates during ATA while providing AV synchronous pacing
      during sinus rhythm and AV block, automatic mode switching (MS) to a nontracking
      mode has been developed. Several concepts of MS algorithms have been introduced
      differing in sensitivity and specificity of ATA detection, delay between ATA
      onset and MS, pacing mode during MS, rapidity of MS termination upon detection of
      sinus rhythm, and special algorithms pertinent to MS. This review classifies and
      analyzes algorithms that are integrated into MS concepts and outlines
      considerations on optimal MS performance. Based on simulations and clinical
      studies, fast MS concepts avoiding high paced ventricular rates seem preferable
      but require special functions to avoid loss of AV synchrony by inappropriate MS.
      Similarly, fast return to tracking mode after ATA cessation seems preferable but
      requires algorithms to prevent mode oscillations. Sudden ventricular rate changes
      have to be avoided by rate smoothing functions, and an appropriate ventricular
      rate during nontracking mode has to be provided by rate responsive pacing.
      Programming of the device includes individual optimization of atrial sensitivity,
      atrial blanking times, and tachycardia detection rates. In addition, a high
      signal-to-noise ratio by careful atrial lead implantation, narrowly spaced
      bipolar atrial leads and a good sensing amplifier, together with special
      algorithms for atrial sensing adjustment improve the performance of MS
      algorithms.

PMID- 11990675
TI  - Evaluating and predicting the ecologic impact of antibiotics.

PMID- 11990676
TI  - The contribution of in vitro bacteriologic experiments.

PMID- 11990678
TI  - How to evaluate and predict the epidemiologic impact of antibiotic use in humans:
      the pharmacoepidemiologic approach.

PMID- 11990677
TI  - Antibiotic resistance: learning from animal feeds and animal experimentation.

PMID- 11990679
TI  - How can we predict the ecologic impact of an antimicrobial: the opinions of a
      population and evolutionary biologist.

PMID- 11990681
TI  - The evaluation and prediction of the ecologic impact of antibiotics in human
      phase I and II trials.

PMID- 11990680
TI  - Making sense of antimicrobial use and resistance surveillance data: application
      of ARIMA and transfer function models.

PMID- 11990682
TI  - How to evaluate the ecologic impact of antibiotics in phase III trials.

PMID- 11990683
TI  - How to evaluate and predict the ecologic impact of antibiotics: the
      pharmaceutical industry view from research and development.

PMID- 11990684
TI  - How to evaluate and predict the ecologic impact of antibiotics: a regulatory
      view.

PMID- 11990685
TI  - In vitro selection of antibiotic resistance in Pseudomonas aeruginosa.

PMID- 11990686
TI  - Quality of antimicrobial drug prescription in hospital.
AB  - There is worldwide concern about the development of antimicrobial resistance [1].
      Selective pressure by antimicrobial drugs is by far the most important driving
      force for the development of resistance. Antimicrobial drugs are among the most
      commonly prescribed drugs in hospitals. In developed countries, some 30% of the
      hospitalized patients will be treated with these drugs. It is generally accepted
      that antimicrobial prescribing is often suboptimal, even in a country like the
      Netherlands, where both antibiotic consumption and microbial resistance rates are
      low [2,3]. The major problem with inappropriate prescribing is because of
      insufficient education in infectious diseases and antimicrobial therapy. Often,
      the prescription of these drugs with little toxicity is unjustified because of
      insecurity about the diagnosis of the clinician; 'drugs of fear' [4]. In our
      surveys, some 15% of the antibiotic prescriptions in surgical and internal
      medicine wards were considered unjustified [5,6]. Many prescribers are not yet
      fully aware that their justified or unjustified prescription adds to the
      resistance problem. In this paper, aspects of the quality of antimicrobial
      prescribing in the hospital setting will be discussed.

PMID- 11990687
TI  - Key issues in developing antibiotic policies: from an institutional level to
      Europe-wide. European Study Group on Antibiotic Policy (ESGAP), Subgroup III.
AB  - Establishment of a rational antibiotic policy (RAP) is a key issue for both
      better care of patients and combating antimicrobial resistance [1-5]. The problem
      of rational antibiotic use is complex [6,7] and requires co-ordination of the
      activities of healthcare authorities, institutions and individual practitioners.
      Furthermore, on a community basis, it involves restriction of non-human usage of
      antibiotics [8] and awareness of society about both the useful and harmful
      effects of antibiotics [9] and, on a national basis, participation of
      governmental [10] and non-governmental [11] organizations in collaboration with
      European and international medical societies [12-14]. The rational use of
      antibiotics should be established in both hospital and ambulatory settings [10].
      Institutional, regional, national and global aspects of antibiotic policies
      should be considered [2].

PMID- 11990688
TI  - The responsibility of the pharmaceutical industry.
AB  - The pharmaceutical industry plays an active role in policy surrounding the
      research, discovery and development of new medicines. Along with this commitment,
      the pharmaceutical industry must also take an active role in helping to ensure
      that appropriate patients receive access to state-of-the-art scientific
      advancements. The various players involved in drug development and introduction,
      including the pharmaceutical industry, clinicians, advocacy groups and regulatory
      bodies, need to work together to ensure patient access to quality care. While
      issues such as drug acquisition costs and marketing are often given a high
      profile, this may cloud perceptions of the industry's commitment to deliver
      important new medicines to the patients and healthcare systems that need them.

PMID- 11990689
TI  - Minimum antibiotic stewardship measures.
AB  - An ESCMID study group on antibiotic policies (ESGAP) was formed in 1998. Several
      subgroups have been formed to develop key strategy in various aspects of
      antibiotic stewardship. Sub group III was formed to lead on antibiotic
      stewardship in European hospitals. This article is a final version of guidelines
      that have been developed by the group through internet discussion. A provisional
      version has been posted on the ESGAP section of ESCMID's website. Some important
      aspects of community antibiotic use have also been included.

PMID- 11990690
TI  - The patient, their doctor, the regulator and the profit maker: conflicts and
      possible solutions.
AB  - The dilemmas and conflicts between industry, who develop and market antibiotics
      and the regulators who are responsible for regulating their use to preserve
      efficacy are explored. Despite regulations, the industry remains profitable and
      should concentrate more on development of innovative products which readily gain
      market share without excessive marketing. Various aspects of regulations are
      discussed as they influence the prescriber and the patient.

PMID- 11990691
TI  - Antibiotics policies; towards consensus between the prescribers, regulators,
      patients and industry?

PMID- 11990692
TI  - Impact of registration procedures on antibiotic policies.
AB  - There is increasing concern over antibiotic resistance and its spread in common
      bacterial species, such as Streptococcus pneumoniae, Staphylococcus aureus,
      Haemophilus influenzae and Escherichia coli. This results in increased morbidity
      and mortality. Over consumption of antibiotics has been reported in many settings
      and underlines the need for improving antibiotic policies. Crude measures of both
      antibiotic use and antibiotic resistance do not share a strong cause-and-effect
      relationship. However, this relationship is highly suggestive at a country level,
      at a hospital level, at a cohort level and at an individual level. In addition to
      overuse, antibiotic misuse has also to be considered, because of its impact on
      promoting antibiotic resistance, related to choice, dosage, dosing regimen or
      duration of therapy [1].

PMID- 11990693
TI  - Conflicts of interest between the prescriber, the regulator and the profit maker.
AB  - The traditional, highly valued, clinical freedom of doctors is under threat with
      the development of evidence-based protocols. Contact with the pharmaceutical
      industry provides doctors with education and resource but at what cost?
      Government has failed to match the industry in this arena. Conflicts of interest
      arise when the balance between the information provided by these two bodies is
      uneven. Authorities' desire for impartial prescribing is not matched by their
      willingness to support the training and working practices which would deliver it.

PMID- 11990694
TI  - Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience.
AB  - PURPOSE: Irinotecan is a novel antineoplastic agent that works by inhibiting the
      enzyme, topoisomerase 1. Although not extensively studied in children,
      preclinical studies and several phase I trials indicate activity against a
      variety of relapsed solid tumors when administered on a protracted schedule. This
      report describes an institutional experience with irinotecan for the treatment of
      pediatric solid tumors. PATIENTS AND METHODS: Twenty-two heavily pretreated
      children with multiply relapsed tumors were treated with courses of irinotecan at
      20 mg/m2 per day for 10 days [(every day x 5) x 2]. RESULTS: Of the 19 patients
      evaluable for response, four achieved an objective response, including two
      complete responses and one partial response among four patients with
      rhabdomyosarcoma and one additional patient with an undifferentiated sarcoma with
      rhabdomyoblastic features, and one patient with a fibrosarcoma had stable
      disease. Among three patients with non-Hodgkin lymphoma, one achieved a partial
      response and one had stable disease. Diarrhea was the most commonly observed
      toxicity. CONCLUSION: Irinotecan appears to have promising single-agent activity,
      particularly against rhabdomyosarcoma. with minimal hematopoietic toxicity,
      making it ideal for further evaluation in patients at high risk with newly
      diagnosed disease, particularly in combination with other active agents with
      nonoverlapping toxicities.

PMID- 11990695
TI  - No major cognitive impairment in young children with acute lymphoblastic leukemia
      using chemotherapy only: a prospective longitudinal study.
AB  - PURPOSE: To study, using serial neuropsychological assessment and evaluation of
      school achievement, persistent neuropsychological late effects in children
      treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy
      only. PATIENTS AND METHODS: Twenty consecutive patients underwent three
      evaluations, including 12 psychometric measures beside IQ. The authors applied
      strict methodology and a prospective-longitudinal design that started at
      diagnosis and extended to a median follow-up of 7 years. This report focuses on
      the outcome of the last evaluation. Test results were compared with healthy
      controls and to patients with ALL treated on a previous chemotherapy-only
      protocol. School achievement was evaluated in patients and their siblings.
      RESULTS: At the last evaluation, significantly lower test scores in patients
      compared with controls were found for only 2 of 14 cognitive measures (1
      intelligence and 1 attention measure). No great differences were seen between
      school achievement of patients and siblings. Compared with the previous
      chemotherapy protocol, a better outcome was seen in the current study group on
      two measures (one memory and one attention measure). CONCLUSIONS: Children
      surviving ALL have no major cognitive impairment after chemotherapy, including
      intrathecal and high-dose intravenous methotrexate. The slightly better outcome
      in the current group may indicate possible adverse effects of more dexamethasone
      treatment in the previous group.

PMID- 11990696
TI  - Cognitive, behavioral, and social outcome in survivors of childhood stem cell
      transplantation.
AB  - PURPOSE: To evaluate prospectively the cognitive functioning and to obtain
      ratings of cognitive, behavioral, and social functioning for children receiving
      stem cell transplantation (SCT). PATIENTS AND METHODS: Forty-seven children
      treated with SCT for malignant or nonmalignant disorders who had no previous
      cranial radiation therapy, no central nervous system tumors, and were aged birth
      to 16 years were administered the Bayley Scales of Infant Development or IQ test
      before SCT and an intelligence test 1 and 2 years after SCT. Children and parents
      rated behavior and social functioning, and parents reported on everyday cognitive
      abilities (including academic ability) 2 to 6 years after SCT. RESULTS: There
      were no statistically significant differences in IQ over the course of time
      (before SCT to 2 years after SCT). Only parent ratings of academic ability were
      significantly lower than the normal standardization sample. Mean mental scale
      scores for children younger than 3 years were lower than mean IQ scores for
      children older than 3 years at the pre-SCT assessment. Mean test scores not only
      decreased for younger children but also were 16 points lower than mean scores for
      older children at 2 years after SCT. CONCLUSIONS: The cognitive, behavioral, and
      social functioning of children 3 years and older is not detrimentally affected 2
      years after SCT. Parents of older children report no cognitive ability problems
      but lower academic ability. Children younger than age 3 years may be at risk for
      decreased cognitive skills.

PMID- 11990697
TI  - Differences in adhesion receptor expression between immature and older platelets
      and red blood cells of neonates and adults.
AB  - PURPOSE: To examine the hypothesis that reticulated platelets and reticulocytes
      show elevated adhesion receptor expression compared with mature cells in both
      adult and neonatal cells. METHODS: Flow cytometry was used to examine laminin,
      fibronectin (VLA-6), and thrombospondin (glycoprotein IV [GPIV]) expression in
      reticulated red cells, reticulated platelets, and older peripherally circulating
      mature red cells and mature platelets in seven newborn cord blood samples and
      blood samples from eight adult volunteers. RESULTS: The difference in the
      neonatal reticulated platelet percentage of 9.2+/-14.8% was not statistically
      significant from the adult reticulated platelet percentage of 5.0+/-1.5% in this
      small population. There was a statistically significant difference between the
      reticulated cord blood red cell mean of 7.7+/-1.8% and the adult mean of 3.1+/
      0.43%. Mean expression of VLA-6 was 96% in adult reticulated platelets, 79% in
      adult mature platelets, 81% in cord reticulated platelets and 65% in cord mature
      platelets. Mean expression of GPIV was similar, with corresponding values of 90%,
      71%, 78%, and 57%. Reticulated red cells in adults averaged 44% VLA-4 and 46%
      GPIV; cord reticulocytes were 9% and 15%, respectively. CONCLUSIONS: Reticulated
      cells newly released from the bone marrow express more adhesive receptors than
      mature cells in both groups. Cord blood samples showed hypoexpression of both
      receptor types in red blood cells and platelets.

PMID- 11990698
TI  - Sickle cell disease: a clinical and histopathologic study of the liver in living
      children.
AB  - PURPOSE: To study hepatic lesions in living children with sickle cell disease.
      Although such lesions are well known, the possibility of chronic persistent
      damage to the parenchyma resulting from the disease itself or iron overload is
      controversial. PATIENTS AND METHODS: Sixteen children with sickle cell disease
      aged 15 months to 18 years were prospectively investigated out of 741 patients
      younger than 20 years registered at Hemominas Foundation, Brazil. Inclusion
      criteria for biopsy were as follows: five had positive anti-hepatitis C virus
      (HCV) antibody, two had positive hepatitis B virus (HBV) surface antigen and
      persistently increased levels of aminotransferases, and nine underwent biopsy
      during abdominal surgery. RESULTS: Children with B or C hepatitis were
      significantly older than the others and also had increased levels of both alanine
      and aspartate aminotransferases. Lobular architecture was preserved in all
      nonviral cases; mild to moderate sinusoidal dilatation was present in eight,
      hepatocellular regenerative activity in six, and focal necrosis and corresponding
      mild inflammatory infiltrate in three. No fibrosis or bile duct damage was
      observed. Mild to severe hemosiderosis was present in all children except one.
      The degree of iron overload was clearly associated with the number of previous
      blood transfusions. All five children with HCV had chronic hepatitis. One of the
      children with HBV had incomplete and the other had definite cirrhosis.
      CONCLUSIONS: These data indicate that chronic hepatic lesions in children with
      sickle cell disease may be caused by viral damage. Patients without evidence for
      viral etiology had reversible vascular lesions. Follow-up studies would be
      necessary to confirm this hypothesis but are precluded for ethical reasons.
      Hemosiderosis was not associated with fibrosis in any nonviral cases, but a
      larger number of patients would be necessary to establish valid conclusions.

PMID- 11990699
TI  - Influence of phenytoin on the disposition of irinotecan: a case report.
AB  - Irinotecan (CPT-11), a water-soluble topoisomerase I inhibitor, is metabolized by
      carboxylesterase enzymes to form an active metabolite, SN-38. Recent studies have
      shown that irinotecan also undergoes oxidative metabolism by the P450 isozyme
      CYP3A4, leading to the formation of a minor inactive metabolite, 7-ethyl-10-[4-N
      [(5-aminopentanoic acid)-1-piperidino]-carbonyloxy-camptothecin (APC). The
      elucidation of this metabolic pathway suggests the potential for drug
      interactions when irinotecan is administered with other inducers or substrates of
      CYP3A4. In this report, the authors summarize the pharmacokinetic profile of
      irinotecan and its major metabolites with and without concomitant phenytoin
      administration in an individual patient. These studies revealed that concomitant
      phenytoin administration resulted in a marked decrease in the systemic exposure
      to irinotecan and SN-38 and an increase in the exposure to APC. The area under
      the curve of irinotecan and SN-38 decreased by 63% and 60%, respectively; the
      area under the curve of APC increased by approximately 16%. Further detailed
      pharmacokinetic studies of irinotecan in patients receiving concomitant therapy
      with enzyme-inducing anticonvulsants are required so that rational dosing
      recommendations can be provided for this patient population.

PMID- 11990700
TI  - Acute myeloid leukemia in a patient with thrombocytopenia with absent radii
      syndrome.

PMID- 11990701
TI  - Human herpesvirus 6 infection mimicking juvenile myelomonocytic leukemia in an
      infant.
AB  - In vitro cell culture studies of bone marrow and peripheral blood progenitor
      cells from patients with juvenile myclomonocytic leukemia (JMML) consistently
      show spontaneous proliferation and selective hypersensitivity to granulocyte
      macrophage colony-stimulating factor (GM-CSF). This GM-CSF hypersensitivity dose
      response assay has become a component of the international diagnostic criteria
      for JMML. The authors report a 2-week-old boy with perinatal human herpesvirus 6
      (HHV-6) infection in whom in vitro bone marrow culture studies suggested the
      diagnosis of JMML by showing increased spontaneous proliferation, inhibition of
      this growth by anti-GM-CSF antibodies, and hypersensitivity to GM-CSF. Polymerase
      chain reaction viral studies from whole blood DNA and the shell vial viral
      culture assay were both positive for HHV-6. The patient's condition improved with
      expectant treatment, with an eventual return to normal blood counts and
      resolution of hepatosplenomegaly. This case of perinatal HHV-6 infection shows
      that viruses can initially mimic the in vitro culture results found in patients
      with JMML. It also illustrates that patients suspected of having JMML should be
      observed if there are no signs of progressive disease and concurrent features
      suggestive of viral infection.

PMID- 11990702
TI  - Unique management of stage 4S neuroblastoma complicated by massive hepatomegaly:
      case report and review of the literature.
AB  - Stage 4S neuroblastoma is an unusual malignancy that has an excellent prognosis,
      except in young infants. A 2-month-old with 4S neuroblastoma complicated by
      massive hepatomegaly, managed by abdominal decompression surgery and a negative
      pressure dressing system is presented. Diffuse alveolar hemorrhage also
      developed, which was treated with high-dose corticosteroids.

PMID- 11990703
TI  - Recurrent polytopic chromaffin paragangliomas in a 9-year-old boy resulting from
      a novel germline mutation in the von Hippel-Lindau gene.
AB  - Pheochromocytomas are frequently associated with inherited cancer syndromes such
      as von Hippel-Lindau disease (VHL). Retinal angioma and hemangioblastomas of the
      central nervous system are hallmarks of VHL, but its clinical variety is
      remarkably broad. Pheochromocytomas as the sole or first manifestation of VHL are
      rare but have been observed. In this case report, the authors describe an unusual
      case of initial collapse, seizures, and hypertensive crisis in a child who later
      was found to have multiple extraadrenal pheochromocytomas. Molecular diagnostics
      revealed a novel point mutation in the VHL gene (VHL nt. 406 T-->G). Only 7
      months after the first lesions had been removed, a new paraganglioma developed in
      the contralateral periadrenal region. When encountering pheochromocytomas in
      children, the clinician should be aware that an associated tumor syndrome might
      be present, and appropriate molecular screening should be initiated. Molecular
      genetics aid in the clinical decision-making and clinical management of
      individual patients with pheochromocytoma.

PMID- 11990704
TI  - Brain metastases in Wilms' tumor: case report and literature review.
AB  - A 2-year-old girl who had a stage 2, favorable-histology Wilms tumor diagnosed
      when she was age 10 months presented with multiple brain metastases at second
      recurrence. She had been treated with combined radiotherapy, surgery, and
      chemotherapy; at 2 months after treatment, recurrent disease developed in the
      central nervous system and she died. Brain metastases are rare in the natural
      history of Wilms tumor. Although it does not appear that cerebral metastases are
      a barrier to tumor eradication and long-term survival if treated with combined
      modality therapy, treatment should be individualized.

PMID- 11990705
TI  - Hepatosplenic gamma/delta T-cell lymphoma with isochromosome 7q, translocation
      t(7;21), and tetrasomy 8 in a 9-year-old girl.
AB  - The authors report a child younger than age 15 years with a rare hepatosplenic
      gamma/delta T-cell lymphoma, which is highly aggressive and primarily seen in
      young men. A 9-year-old girl presented with thrombocytopenia and
      hepatosplenomegaly. Bone marrow analysis revealed a metastatic pleomorphic
      lymphoma of peripheral T-cell phenotype, with rearrangement of the T-cell
      receptor gamma/delta and expression of CD3 and CD16/56. Instead of the previously
      reported primary, nonrandom, chromosomal abnormalities, isochromosome 7q and
      trisomy 8, this patient had four copies each of chromosome 7q, including
      isochromosome 7[i(7)(q10)] and der(21)t(7;21), as well as chromosome 8. This
      entity needs to be considered in women and children with lymphoma. Conventional
      therapy appears to be inadequate for cure.

PMID- 11990706
TI  - Mesenteric inflammatory pseudotumor: unusual presentation with leukemoid reaction
      and massive calcified mass.
AB  - The authors describe a child with an unusual presentation of mesenteric
      inflammatory pseudotumor in association with leukemoid reaction. An 11-year-old
      boy admitted with short stature was found to have an abdominal mass localized in
      the right lower quadrant. The leukocyte count was 92,000/mm3 with neutrophilic
      leukemoid reaction. Abdominal ultrasonography and computed tomography revealed a
      massive calcified mass in the pelvis. Total resection of the mass was performed
      and the pathologic diagnosis of inflammatory pseudotumor of the mesentery was
      made. Leukemoid reaction dramatically resolved within a few days after surgical
      resection. Physicians should be aware of the association of inflammatory
      pseudotumor, leukemoid reaction, and massive calcification.

PMID- 11990707
TI  - Neutrophil dysfunction in a case of glucose-6-phosphate dehydrogenase deficiency.

PMID- 11990708
TI  - Testing new agents: can we move beyond DLT?

PMID- 11990709
TI  - Clinical trials using irinotecan.

PMID- 11990710
TI  - More good news about neuropsychological late effects in long-term survivors of
      acute lymphoblastic leukemia.

PMID- 11990711
TI  - Pediatric acute lymphoblastic leukemia: redefining outcomes.

PMID- 11990712
TI  - Phase I trial of cisplatin and topotecan in children with recurrent solid tumors:
      Children's Cancer Group Study 0942.
AB  - OBJECTIVES: To determine the maximum tolerated dose (MTD) and dose-limiting
      toxicities (DLTs) of cisplatin after a 72-hour continuous infusion of topotecan.
      PATIENTS AND METHODS: Thirty-six children younger than age 22 years (range 3-21)
      with recurrent solid tumors were treated with cisplatin 45 to 75 mg/m2 infused
      over the course of 6 hours, followed by a 72-hour continuous infusion of
      topotecan 0.75 or 1 mg/m2 per day, followed by granulocyte colony stimulating
      factor (G-CSF), either immediately after treatment or when neutropenia developed.
      Patients were stratified by the presence of bone marrow tumor involvement and
      previous radiation to the bone marrow. RESULTS: The DLT was neutropenia (absolute
      neutrophil count <500/microL for >7 days). The MTD was cisplatin 60 mg/m2 and
      topotecan 1 mg/m2 per day followed by G-CSF starting 24 hours after chemotherapy
      for patients without marrow involvement or previous radiation to the bone marrow.
      An acceptable MTD was not found for patients with previous radiation to the bone
      marrow or bone marrow involvement or without the use of G-CSF starting 24 hours
      after chemotherapy was completed. Topotecan clearance and steady-state levels
      were determined. Limited evidence for antitumor activity with this combination
      was found in rhabdomyosarcoma. CONCLUSIONS: The recommended dose for phase II
      trials is cisplatin 60 mg/m2 followed by a 72-hour infusion of topotecan 1 mg/m2
      per day with G-CSF starting 24 hours after the completion of topotecan.

PMID- 11990713
TI  - Phase I study of irinotecan in pediatric patients with malignant solid tumors.
AB  - PURPOSE: To determine the dose-limiting toxicity, maximum tolerated dose, and
      potential efficacy of irinotecan in children with refractory malignant solid
      tumors. PATIENTS AND METHODS: In the present phase I clinical trial, 28 patients
      received irinotecan 50 to 200 mg/m2 per day by intravenous 2-hour infusion over
      the course of 3 days, repeated once after an interval of 25 days. Fifty-one
      treatment courses were administered to these patients. RESULTS: Dose-limiting
      toxicities were observed at the dose of 200 mg/m2 per day for 3 days. Diarrhea
      and hematopoietic toxicities were the dose-limiting factors, and the former
      required support with intravenous fluid administration. The occurrence of
      vomiting was variable. Decreases in clinical tumor marker levels were observed in
      the majority of patients who received two cycles of irinotecan 80 mg/m2 per day
      to 200 mg/m2 per day over the course of 3 days, and partial response was attained
      in four patients who received irinotecan in two cycles of 140 mg/m2 per day to
      200 mg/m2 per day over the course of 3 days. Pharmacokinetic studies showed that
      the plasma concentration of irinotecan and its active metabolite SN-38 ranged
      from 93 to 2,820 ng/mL and 5.2 to 34.8 ng/mL, respectively, during 3-day
      infusions of irinotecan 200 mg/m2 per day. The mean clearance of irinotecan was
      14.54 L/h per m2 (range 8.45-20.83 L/h per m2). CONCLUSION: The maximum tolerated
      dose was determined to be a dose of irinotecan between 160 mg/m2 per day and 180
      mg/m2 per day administered over the course of 3 consecutive days on an inpatient
      basis, repeated once after 25 days off, and our results indicate that irinotecan
      is a promising anticancer agent that is worthy of phase II trials in pediatric
      solid tumors.

PMID- 11990714
TI  - Objective measurement of nasal airway dimensions using acoustic rhinometry:
      methodological and clinical aspects.
AB  - INTRODUCTION: Nasal congestion is an important symptom in many diseases of the
      upper airways. Nasal congestion may also affect personal well-being and quality
      of life. Furthermore, as the nasal mucosa is the first part of the airways in
      contact with the environment, objective evaluation of nasal congestion or nasal
      patency is important. Systematic evaluation of nasal patency was described in the
      last part of the 19th century by Zwaardemaker. Measurement of the pressure drop
      over the nasal cavity at a passive dow has been described in 1903 by Courtade and
      is one of first descriptions rhinomanometry. The technique is still in use and
      computer technology has made the measurements much easier but the method has not
      yet been accepted for wide clinical use. METHODOLOGY: Acoustic methods have also
      been used for evaluation of nasal patency. A qualitative method was the hum-test
      by Spiess (1902), where external occlusion of the nonocciuded side of the nasal
      cavity is experienced as a change in the timbre of the sound during humming.
      Acoustic reflections have been used in geophysical investigations especially with
      regard to search for oil. The use of acoustic reflections from the airways gained
      special interest in 1960-70 for determining the geometry of the vocal tract shape
      with regard to speech reconstruction. A method described by A. Jackson (1977) was
      adopted and for the first time applied to the nasal cavity. The method for
      determining the cross-sectional area as function of distance in the airways by
      acoustic reflections is impulse or relatively simple. The incident sound
      pseudorandom noise in the audible frequency range is compared with the response -
      the reflections from the airways. Intuitively, if the size of the entrance to the
      airways is known, the size of the reflections may represent changes of the airway
      size and the time between reflections may give the distance between the changes,
      dependent on the speed of sound. In this way it is possible to determine the area
      as function of distance in the airways. The technique has some assumptions and
      the major effort has been to validate use in the nose and elucidate aspects with
      regard to sound loss in the airways and resolution. Therefore, the acoustic
      reflection technique - named acoustic rhinometry - was compared with other
      methods like MRI, CT, and rhinomanometry. Allergic and nonallergic subjects were
      also compared. RESULTS: Acoustic rhinometry showed reasonable correlation with CT
      in a cadaver and in 10 subjects in comparison with MRI for the first 6 cm of the
      nasal cavity. Models based on MRI scannings of subjects also showed good
      correlation for the first 6 cm of the nasal cavity. Posteriorly in the nasal
      cavity and the epipharynx, differences were found mainly due to 'sound loss' to
      the paranasal sinuses. Sound loss due to viscous loss or friction at increasing
      surface/area ratio (the complex geometry in the nose) and loss due to nonrigidity
      the nasal mucosa were also examined. Neither these factors affected the area
      distance function significantly. Acoustic rhinometry seems to reflect the area
      distance function in the nose reasonably accurately. In allergic subjects
      acoustic rhinometry has been used to evaluate hypersensitivity. More pronounced
      spontaneous variation in nasal mucosa congestion was found in patients suffering
      from hay fever compared to nonallergic subjects. Furthermore, a tendency to a
      more swollen mucosa in the allergic subjects compared to the normal state, and
      increased sensitivity to histamine was found. This and reduction in swelling of
      the mucosa in allergic subjects during nasal steroid treatment out of the pollen
      season indicate an ongoing inflammatory process or hypersensitivity in allergic
      subjects out ot the pollen season. During allergen challenge the change in nasal
      cavity dimension as well as inflammation may affect olfaction in hay fever
      patients. DISCUSSION: Acoustic rhinometry has not only been used to examine hay
      fever patients but in many different aspects of rhinology. Since the introduction
      of the acoustic reflection technique in the nose more than papers using the
      technique have been published. Most of the papers find the technique valuable for
      evaluation of nasal patency. Fortunately, some critical papers have drawn
      attention to some practical aspects of the technique. Standard operating
      procedures, and calibration checks as well as training operators will enhance the
      accuracy and reproducibility of results. CONCLUSION AND PERSPECTIVES: A decade
      after its introduction acoustic rhinometry is a well-established method for
      evaluation of nasal patency, but further improvement can be obtained by continued
      validation and adjustments of the technique.

PMID- 11990715
TI  - Behavioural and pharmacological relevance of stroke-prone spontaneously
      hypertensive rats as an animal model of a developmental disorder.
AB  - The present study evaluates juvenile stroke-prone spontaneously hypertensive rats
      (SHRSP) as an animal model of a developmental disorder, which is diagnosed
      according to hyperactivity-impulsivity and/or inattention. To characterize
      behavioural alterations, we studied motor activity, as well as emotional and
      cognitive behaviours in juvenile SHRSP, with and without methylphenidate, a
      psychostimulant. Ambulatory and rearing activities in the open-field environment
      were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY). In the
      elevated plus maze task, the entries into open arms, as an index of impulsivity,
      were significantly increased in SHRSP. In the Y-maze task, spontaneous
      alternation behaviour, as an index of attention, was significantly lowered in the
      male SHRSP, but not in the female SHRSP, indicating that spontaneous alternation
      deficit is gender specific. Methylphenidate (0.01-1 mg/kg, i.p.) significantly
      attenuated locomotor hyperactivity at low doses and dose-dependently improved the
      spontaneous alternation deficit in SHRSP. Our findings reveal that juvenile SHRSP
      manifest problematic behaviours resembling a developmental disorder, attention
      deficit/hyperactivity disorder (ADHD), namely hyperactivity-impulsivity and/or
      inattention. Methylphenidate alleviated the behavioural symptoms of hyperactivity
      and inattention. We propose that juvenile SHRSP are an appropriate animal model
      of a developmental disorder resembling ADHD, from behavioural and pharmacological
      perspectives.

PMID- 11990716
TI  - Differing effects of the cannabinoid agonist, CP 55,940, in an alcohol or Tween
      80 solvent, on prepulse inhibition of the acoustic startle reflex in the rat.
AB  - It has been suggested that cannabinoid agonists increase dopamine (DA)
      transmission in the mesolimbic dopamine system. However, evidence for such an
      effect is inconsistent. Prepulse inhibition (PPI) of the acoustic startle reflex
      is a behavioural paradigm that is modulated by an increase of mesolimbic
      dopamine. This study sought to ascertain whether or not a cannabinoid agonist, CP
      55,940, mimicked the effects of amphetamine (a drug which increases dopamine
      release) on PPI. The first experiment measured the PPI of 16 male Wistar rats
      injected (i.p.) with different doses of CP 55,940 in a Latin-square design. A
      second experiment replicated the effects of the first experiment in a between
      subjects design, and also examined the effects of using a 5% alcohol solution as
      a solvent for cannabinoid agonists, in comparison to the more inert detergent,
      Tween 80. In both experiments, CP 55,940 in Tween 80 significantly reduced basal
      activity, increased startle onset latencies and increased PPI, effects opposite
      to those of amphetamine. These results suggest that the net behavioural effects
      of cannabinoids are opposite to those of amphetamine. In addition, it was found
      that 1 ml/kg of a 5% alcohol solution has significant behavioural effects on its
      own, and reverses the effects of CP 55,940 on PPI.

PMID- 11990717
TI  - The cannabinoid agonist WIN 55,212-2 reduces sensorimotor gating and recognition
      memory in rats.
AB  - Cannabinoids can disrupt short-term memory in humans and animals and induce
      learning deficits and other cognitive impairments. In the present study we
      examined the role of a full cannabinoid agonist in short-term memory,
      sensorimotor gating, and the acquisition and expression of an operant learning
      paradigm in rats. We tested the effects of the synthetic cannabinoid WIN 55,212-2
      (0.6 and 1.2 mg/kg) on short-term memory in social and object recognition tests,
      on prepulse inhibition (PPI) of startle, as well as on lever pressing for
      palatable food. Injections of 0.6 and 1.2 mg/kg WIN 55,212-2 impaired recognition
      memory and PPI in a dose-dependent manner, but had no effect on lever-pressing
      acquisition or expression, or on food preference. The PPI deficit was reversed by
      the administration of 0.1 mg/kg haloperidol. These data suggest that the
      synthetic cannabinoid WIN 55,212-2 does not lead to a general impairment of
      learning in an appetitive instrumental task, but significantly affects short-term
      memory and sensorimotor integration. The impairment in recognition and PPI might
      be due to deficits in attention-based short-term information processing.

PMID- 11990718
TI  - The effects of extrinsic context on nicotine discrimination.
AB  - There is evidence from memory studies that context acquired in parallel with the
      encoded material will facilitate retrieval. However, relatively little is known
      of how context affects drug discrimination behaviour in humans. The present study
      employs conventional drug discrimination procedures to investigate the effects of
      music, as an external cue, on nicotine drug discrimination. Subjects were trained
      to discriminate a low dose of nicotine (1 mg) from placebo while listening to two
      different types of music [elated (EL) and depressant (DE): thought to induce
      happy and sad mood respectively]. Half of the subjects received EL music with
      nicotine and DE with placebo and the other half vice versa. At the end of
      training, subjects who reached the criterion (80% of trials identified correctly)
      entered the generalization phase and were required to discriminate different
      doses of nicotine (0, 0.25, 0.5 and 1 mg) by indicating how similar each sample
      was to the training dose. Generalization took place in the presence of either EL
      or DE music. Nicotine-appropriate responding during generalization was linearly
      related to dose, with subjects being able to distinguish 0.5mg of nicotine from
      placebo. Nicotine-appropriate responding at generalization was higher when the
      context (type of music) was the same as the one employed during discrimination
      training when nicotine was administered (i.e. a context-dependent generalization
      effect was present). In addition, it was shown that the context-dependent effect
      was due to the properties of the EL music. These data provide the first evidence
      that extrinsic context can facilitate nicotine discrimination in humans. In
      addition, the findings suggest that this facilitatory effect is not a general
      effect but is sensitive to specific attributes of the context.

PMID- 11990719
TI  - Drug trace discrimination with nicotine and morphine in rats.
AB  - In typical drug discrimination experiments, subjects are exposed to psychoactive
      substances both prior to and during training sessions. The present experiments
      aimed to determine whether pre-session effects of drugs could serve as
      discriminative stimuli. Rats were trained in a two-lever discrimination procedure
      with food reinforcers presented on a tandem variable interval-fixed ratio (VI-FR)
      schedule. Injections of nicotine (0.6mg/kg 20 min pre-session) or saline were
      followed by administration of the nicotine antagonist mecamylamine (1.0 mg/kg 10
      min pre-session) to block effects of nicotine during training sessions.
      Similarly, the action of morphine (10 mg/kg 30 min pre-session) was terminated by
      administering naloxone (0.1 mg/kg 10 min pre-session). These drug discriminations
      were acquired slowly to an accuracy of only 70-75% (n=10-12). Extinction tests
      confirmed stimulus control by nicotine in the presence of mecamylamine and by
      morphine in the presence of naloxone. The antagonists attenuated the response
      rate reducing effects of the training doses of their respective agonists. The
      results are interpreted in terms of stimulus control by pre-session effects of
      the training drugs, but other explanations are considered. Stimulus control by
      pre-session drug states may be weak due to the time elapsed between termination
      of drug effects and training (trace conditioning).

PMID- 11990720
TI  - Conditioned hyperkinesia induced by cocaine in mice is dose-dependent but not
      correlated with the unconditioned response or the contextually-sensitized
      response.
AB  - The aims of the study were to test whether drug dose is positively related to the
      magnitude of the conditioned response following sensitization to the behavioural
      effects of cocaine and to investigate the relationship between the conditioned
      response and cocaine-induced sensitization. Male mice (C57BL/6J) were first
      injected over seven successive days with either saline or cocaine at 2.5, 5, 10
      or 20 mg/kg s.c., in the testing room. On the test day, 24 h after the last
      injection, mice from all conditions were challenged with saline in the testing
      room to test for conditioned cocaine effects. Mice were video-recorded and
      various behaviours were later scored using a time-sampling technique. Cocaine
      elicited orofacial stereotypy was significantly sensitized at the two highest
      doses and dose-dependently conditioned at the three highest doses. Cocaine
      increased locomotion was sensitized at the three highest doses and significantly
      conditioned at 10 and 20mg/kg. Cocaine-increased sniffing did not change over
      pretreatment at any dose, and was conditioned only at 10 mg/kg. Cocaine-decreased
      immobility also did not change over pretreatment at any dose, but was conditioned
      at 10 and 20mg/kg. Concomitantly, rearing was reduced by cocaine at 10 and
      20mg/kg, without sensitization being induced, and it was reduced under saline
      challenge after 5 mg/kg cocaine, while cocaine-decreased grooming was sensitized
      at the three highest doses and conditioned at 10 and 20 mg/kg cocaine. There was
      a positive relation between the size of the conditioned response for orofacial
      stereotypy and the magnitude of the unconditioned stimulus (the doses), a result
      conforming to the Pavlovian account of the placebo effect. This could also be
      concluded from considering the behaviour patterns as components of a unique
      placebo effect (hyperkinetic syndrome), since orofacial stereotypy, very apparent
      at 20 mg/kg cocaine, interfered at that dose with the full-blown expression of
      locomotion and sniffing, both yielding (approximately) inverted U-shaped dose
      effect curves. However, no correlation was found between the magnitude of the
      conditioned response and the amplitude of sensitization (the difference between
      the initial unconditioned non-sensitized response and the last unconditioned
      sensitized response), a finding which indicates that conditioned responding does
      not participate in the generation of the sensitized effects, contrary to the
      'excitatory conditioning model of contextual sensitization'.

PMID- 11990721
TI  - Further evidence for the involvement of histamine H2 receptors in the control of
      defensive behaviour generated in the midbrain tectum.
AB  - The dorsal periaqueductal grey matter (dPAG) and inferior colliculus (IC) have
      been implicated in the control of defence reactions. Electrical and chemical
      stimulation of these structures induces escape behaviour, usually accompanied by
      autonomic responses and decreased pain sensitivity. Recently, we presented
      evidence for an involvement of histamine in the generation and organization of
      such defensive reactions in the midbrain tectum. In this study we have used the
      open field test to assess the effects of microinjections of histamine (40 nmol),
      dimaprit (10 nmol) and ranitidine (50 nmol) into the midbrain tectum of rats.
      Dimaprit is an agonist and ranitidine an antagonist of H2 histamine receptors.
      Immediately after the injections the animals were tested in an open field for 60
      min. In an additional groups of rats, dimaprit was injected 15 min before the
      microinjections of ranitidine into either the dPAG or the IC. The results show
      that whereas histamine preceded by saline did not cause any apparent behavioural
      changes, ranitidine led to a behavioural reaction, with clear signs of fear,
      which was blocked by previous injection of dimaprit. Injections of only dimaprit
      had no apparent effects. The present results suggest that H2 receptors may be
      involved in the control of defensive behaviour following activation of the neural
      substrates of fear in the dPAG and IC.

PMID- 11990722
TI  - Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on
      methylphenidate-induced hyperlocomotion in mice.
AB  - The psychostimulant methylphenidate (MPD) is used for the treatment of attention
      deficit/hyperactivity disorders (ADHD) in adolescents. In the present study we
      investigated the effect of repeated administration of a low (10 mg/kg) and a high
      (40 mg/kg) dose of MPD on the locomotor activity of Swiss Webster mice, and the
      influence of inhibition of the neuronal nitric oxide synthase (nNOS) on MPD
      induced hyperlocomotion. In the first experiment, mice were administered either
      vehicle or the nNOS inhibitor 7-nitroindazole (7-NI; 25 mg/kg), prior to the
      administration of MPD (10 or 40 mg/kg), for five consecutive days; injections
      were paired with the test cage ('novel environment') on days 1 and 5. A challenge
      injection of MPD (10 or 40 mg/kg), given after a 10-day drug-free period,
      resulted in sensitization to the motor stimulating effect of the low dose of MPD
      but tolerance to the high dose of MPD. 7-NI blocked the induction of
      sensitization but had no effect on the development of tolerance. The place
      dependent-hyperlocomotion (e.g. conditioning) that developed after the
      administration of either the low or high dose of MPD was blocked by pretreatment
      with the nNOS inhibitor. In the second experiment, mice were administered MPD (10
      or 40 mg/kg; 5 days) in their home cage and after a 10-day drug-free period were
      challenged with either vehicle/MPD or 7-NI/MPD. The low dose of MPD elicited a
      sensitized response that was blocked by the co-administration of 7-NI. The high
      dose of MPD produced neither sensitization nor tolerance; 7-NI did not affect the
      response to the high dose of MPD. These findings suggest: (a) MPD-induced
      sensitization and tolerance are dependent on the dose of the drug and the
      environment where the drug is delivered (home cage versus test cage); (b) context
      dependent hyperlocomotion developed in the absence of a sensitized response to
      the drug; (c) nNOS is involved in the induction and expression of sensitization
      to MPD as well as in the conditioned locomotion produced by the drug; (d) no
      involvement of nNOS in the effects of a high dose of MPD was detected.

PMID- 11990723
TI  - Baclofen prevents morphine withdrawal irrespective of seasonal variation.
AB  - In previous studies we have demonstrated a possible interaction between the gamma
      aminobutyric acid (GABA)ergic and opioid systems involved in the antinociceptive
      effect of the GABAB agonist, baclofen (BAC). In addition, we have demonstrated
      that BAC was able to prevent the morphine (MOR) withdrawal syndrome in female, as
      well as male mice. On the other hand, seasonal variations have been observed in
      some MOR effects. In the present study, we analysed the effects of BAC on
      naloxone (NAL)-precipitated withdrawal, during two different seasons. The
      experiments were performed during two seasons: spring-summer (SS) and autumn
      winter (AW) for two years, on male Swiss-Webster albino mice (27-33 g). Mice were
      rendered dependent by intraperitoneal (i.p.) injection of MOR (2mg/kg), twice
      daily for 9 days. On the tenth day the dependent animals were divided into two
      groups: one received NAL (6mg/kg, i.p.) 60 min after the last dose of MOR, to
      develop the NAL-precipitated withdrawal; the other group received BAC (2mg/kg,
      i.p.) followed by NAL (6mg/kg, i.p.), injected 30 and 60 min after the last dose
      of MOR, respectively. Behavioural signs were recorded in the open field for 30
      min. Although there were seasonal variations in the MOR withdrawal syndrome, we
      found that BAC prevents MOR withdrawal irrespective of seasonal variation.

PMID- 11990724
TI  - Increased plasma concentrations of intercellular adhesion molecule-1 after
      strenuous exercise associated with muscle damage.
AB  - Intercellular adhesion molecule-1 (ICAM-1) plays an important role in leukocyte
      migration from the circulation and intervention at sites of inflammation. We
      investigated the effects of various types of exercise on circulating levels of
      soluble ICAM-1 (sICAM-1) in normal healthy male adults. Plasma concentrations of
      sICAM-1 were measured before and after bicycle ergometer exercise at intensity of
      80% maximal oxygen consumption (VO2mag) (16 min), 42 km endurance running and 30
      min downhill running at intensity of ventilation threshold (VT). The plasma sICAM
      1 level increased 1 day after the endurance running (12%) and downhill running
      (14%), but not after ergometer exercise. Plasma C-reactive protein (CRP) and
      creatine kinase (CK) concentrations also increased 1 day after running. Our data
      suggest that exercise associated with muscle damage and/or inflammation results
      in increased levels of plasma sICAM-1. The physiological significance of post
      exercise high plasma sICAM-1 levels is not clear at this stage, but changes in
      plasma sICAM-1 may reflect the status of the immune system.

PMID- 11990725
TI  - Effect of arm cranking on the NIRS-determined blood volume and oxygenation of
      human inactive and exercising vastus lateralis muscle.
AB  - In this study, the effects of arm cranking on total (HbT) and oxygenated
      haemoglobin concentrations (HbO2) of inactive and exercising vastus lateralis
      muscles were investigated using near-infrared spectrometry (NIRS). Four exercise
      protocols were performed, 6-min arm cranking at intensities of 30% and 50% of
      peak oxygen uptake (VO2peak, recorded during incremental arm exercise; AE30 and
      AE50, respectively), and 6 min of combined exercise in which AE30 or AE50 was
      added to on-going leg cycling at an intensity of 40% VO2peak (LE40: AE30LE40 and
      AE50LE40, respectively). During AE30 in the inactive vastus lateralis, neither
      HbT nor HbO2 changed from the control values, whereas they both decreased during
      AE50. The decrease in HbT was observed from the 1st to the 5th min of exercise,
      whereas the decrease in HbO2 was observed from the 3rd to the 6th min of
      exercise. In the exercising vastus lateralis, neither HbT nor HbO2 changed from
      the control value during AE30LE40. In addition, HbO2 did not change during
      AE50LE40. During AE50LE40, however, although HbT did not change from the 1st to
      the 4th min of exercise, it increased from the 4th to the 6th min. These results
      indicate that although in the inactive vastus lateralis both HbT and HbO2
      decrease during moderate arm exercise, these decreases are suppressed in the
      exercising vastus lateralis muscle.

PMID- 11990726
TI  - Renal handling of salt and water in humans during exercise with or without
      hydration.
AB  - Plasma sodium (Na+) concentration, i.e. natraemia, results from body tonicity
      equilibrium. During exercise, a change in body tonicity can result from an
      imbalance between intake and loss of Na+, potassium (K+) and water (H2O) due to
      renal and/or extra-renal mechanisms. Whether exercise-induced changes in kidney
      function could be responsible for such an imbalance was studied by measuring
      glomerular filtration rate (creatinine clearance), proximal tubule activity
      (lithium clearance) and renal handling of Na+ and K+ at rest and during exercise.
      Since hyponatraemia during or after exercise has been reported, we also
      investigated whether a water load could be appropriately excreted during
      exercise. Ten young men pedalled on a cycle ergometer at 60% of maximal oxygen
      uptake for 45 min with (HE, hydrated exercise) or without (DHE, dehydrated
      exercise) a supply of water. In both conditions, creatinine, lithium, and
      electrolyte (Na+ + K+) clearances decreased and natraemia did not change. The DHE
      induced a loss of body mass (-1.29%), decreased diuresis and large extra-renal
      water loss [mean (SEM)] [880 (73) ml]. The HE led to no loss in body mass,
      increased diuresis and lower extrarenal water loss [680 (48) ml]. Electrolyte
      free water excretion, negative for DHE, represented 60% of diuresis during HE.
      Thus the kidney, by increasing electrolyte reabsorption mainly in the proximal
      tubule, and appropriately excreting a water load, seems efficacious in regulating
      extracellular fluid volume and body tonicity and so not responsible for the
      imbalance between (Na+ + K+)/H2O intake and loss. Therefore, extra-renal changes
      could be the main causes of exercise-induced tonicity imbalances which could
      ultimately lead to dysnatraemia.

PMID- 11990727
TI  - Validity of ultrasonograph muscle thickness measurements for estimating muscle
      volume of knee extensors in humans.
AB  - This study aimed to investigate the suitability of using ultrasonograph muscle
      thickness (MT) measurements to estimate the muscle volume (MV) of the quadriceps
      femoris as an alternative approach to magnetic resonance imaging (MRI). The
      subjects were 46 men aged from 20 to 70 years who were randomly allocated to
      either a validation or a cross-validation group. In the validation group,
      multiple and simple regression equations, which used a set of MT values
      determined at mid-thigh and thigh length (1) and the product of pi, (MT/2)2, and
      l [pi x (MT/2)2 x l], respectively, as independent variables, were derived to
      estimate the MV measured by MRI. Because the two equations were cross-validated,
      the data from the two groups were pooled to generate the final prediction
      equations: MV (cm3)=(MT x 311.732)+(l x 53.346) -2058.529 as the multiple
      regression equation and MV (cm3) = [pi x (MT/ 2)2 x l] x 1.1176+663.040 as the
      simple regression equation. In the multiple regression equation, MT explained 75%
      of the variation in the MV measured by MRI. The r2 and the standard error of the
      estimate (SEE) of the equations were 0.824 and 175.6 cm3 (10.6%), respectively,
      for the multiple regression equation and 0.829 and 173.7 cm3 (10.5%),
      respectively, for the simple regression equation. Thus, the present results
      indicate that ultrasonograph MT measurements at mid-thigh are useful for
      estimating the MV of knee extensors. However, the observed SEE values suggest
      that the prediction equation obtained in this study may be limited to population
      studies rather than individual assessments in longitudinal studies.

PMID- 11990728
TI  - Small amounts of venous gas embolism cause delayed impairment of endothelial
      function and increase polymorphonuclear neutrophil infiltration.
AB  - Gas bubbles from decompression and gas embolization lead to endothelial
      dysfunction and mechanical injury in the pig, rabbit and lamb. In the study
      presented here, 0.01 ml air/min/kg was infused through a catheter into the
      jugular vein in 12 rabbits for 60 min. The endothelial response was measured
      using tension measurements in the blood vessel wall, and morphological changes
      where quantified using light microscopy and image processing. Percent lung water
      content was calculated and used to estimate the severity of pulmonary oedema. The
      infusion led to a significant decrease in the acetylcholine-mediated endothelial
      dependent vasodilatation in the pulmonary artery 6 h after the infusion (6-h
      group, n = 6). A decrease in substance-P-mediated endothelial-dependent
      vasodilatation was also detected. No changes where seen in a group of rabbits
      examined 1 h after infusion (l-h group, n=6). The impaired endothelial-dependent
      vasodilatation caused by the bubbles is probably biochemical in origin, since no
      visible changes were seen in the endothelial layer. A significant increase in
      polymorphonuclear neutrophils was observed in the 6-h group compared to the l-h
      group. This study demonstrates that small numbers of bubbles, corresponding to
      "silent bubbles", lead to an impairment of the endothelial-dependent vasoactive
      response.

PMID- 11990729
TI  - Effects of crank length on maximal cycling power and optimal pedaling rate of
      boys aged 8-11 years.
AB  - It is generally reported that cycle crank length affects maximal cycling power of
      adults and that optimal crank length is related to leg length. This suggests that
      the use of standard length cycle cranks may provide nonoptimal test conditions
      for children. The purpose of this study was to determine the effects of cycle
      crank length on maximal cycling power and optimal pedaling rate of 17 boys aged 8
      11 years. The boys performed maximal cycle ergometry with standard (170 mm) cycle
      cranks and with a crank length that was 20% of estimated leg length (LL20). Power
      produced when using the 170 mm cranks [mean (SEM)] [364 (18) W] did not differ
      from that produced with the LL20 cranks [366 (19)]. Optimal pedaling rate was
      significantly greater for the LL20 cranks [129 (4) rpm] than for the 170 mm
      cranks [114 (4) rpm]. These data suggest that standard 170 mm cranks do not
      compromise maximal power measurements in boys aged 8-11 years so that the test
      apparatus does not bias physiological or developmental inferences made from tests
      of maximal cycling power.

PMID- 11990730
TI  - Heritability of explosive power and anaerobic capacity in humans.
AB  - There is a disparity in the information about the heritability of the response of
      muscle anaerobic metabolism to exercise and the use of explosive power, as well
      as a lack of information concerning the genetic determinants of this form of
      work, as measured using different specific physical tests. We applied a battery
      of some of the commonly employed procedures (Ergojump, Wingate, maximal
      accumulated oxygen deficit, excess post-exercise oxygen consumption, and delta
      lactate concentration) to a group of 32 Caucasian male twins, 8 monozygotic and 8
      dizygotic pairs, who had similar environmental backgrounds. Results were studied
      using a heritability index (HI). Zygosity was determined using the identity of
      erythrocyte antigens, protein and enzyme polymorphism and human leucocyte antigen
      serologic types between co-twins. Significant HI values (P< 0.05) were found in
      the following tests: maximal 5 s power (HI = 0.74) and total power in a 30 s
      interval (HI = 0.84) in the Wingate test, maximal lactate concentration (HI =
      0.82) and delta lactate concentration (HI = 0.84) in the maximal progressive
      test, as well as in the 2nd (HI = 0.93) and in the 3rd min (HI = 0.92) of
      recovery after the deficit test. In this study, the most relevant findings were:
      firstly, significant HI values for many of the variables studied; secondly, the
      HI values of the parameters used to evaluate explosive power were higher than
      those of lactic acid capacity and thirdly, the HI of certain variables from
      different tests measuring, in theory, similar qualities, were different.

PMID- 11990731
TI  - The relationships among peak torque, mean power output, mechanomyography, and
      electromyography in men and women during maximal, eccentric isokinetic muscle
      actions.
AB  - The purpose of the present investigation was to examine the velocity-related
      patterns of peak torque (PT), mean power output (MP), mechanomyographic (MMG)
      amplitude, and electromyographic (EMG) amplitude of the vastus lateralis (VL)
      muscle in men and women during maximal, eccentric isokinetic muscle actions of
      the leg extensors. Eight women [mean (SD)] [aged 23 (3) years] and seven men
      [aged 23 (2) years] volunteered for this investigation. Their PT was measured on
      a calibrated dynamometer at randomly ordered velocities of 30, 90, and 150
      degrees x s(-1). A piezoelectric MMG recording sensor was placed between bipolar
      surface EMG electrodes (Ag-AgCl) over the VL muscle. Their MP was determined
      using the dynamometer software. The results indicated no sex-related differences
      (P > 0.05) for the patterns of PT, MP, MMG amplitude, or EMG amplitude across
      velocity. The normalized values for MP and MMG amplitude increased (P<0.05) from
      30 to 150 degrees x s(-1) (30 degrees x s(-1) <90 degrees x s(-1) < 150 degrees x
      s(-1)), while PT and EMG amplitudes remained unchanged across velocity. The
      results indicated close associations between the velocity-related patterns of MP
      and MMG amplitudes as well as PT and EMG amplitudes. Thus, MMG amplitude
      reflected the velocity-related changes in muscle power output, but not torque
      production, while EMG amplitude reflected torque production, but not muscle power
      output. During maximal, eccentric isokinetic muscle actions, EMG and MMG signals
      provided unique information regarding the electrical and mechanical aspects of
      muscle strength and power.

PMID- 11990732
TI  - Misuse of androgenic-anabolic steroids and human deltoid muscle fibers:
      differences between polydrug regimens and single drug administration.
AB  - The objective of this investigation was to study the effects of androgenic
      anabolic steroid (AAS) misuse on deltoid muscle fiber characteristics in
      experienced, male strength-trained athletes. In a double-blind study, 15
      volunteers were administered nandrolone decanoate (ND) for 8 weeks (200 mg/week,
      intramuscularly). In an additional study, 12 subjects self-administered various
      AASs at supratherapeutic dosages (AAS group), while 7 non-users served as
      controls. In all subjects, a percutaneous needle biopsy sample of the deltoid
      muscle was obtained at baseline and after 8 weeks. Muscle sections were pre
      incubated at pH 4.4, stained with adenosine triphosphatase and analyzed
      morphometrically. In each biopsy sample, at least 150 fibers were classified for
      "gray level" and "lesser fiber diameter" to determine the mean fiber size, the
      sizes of type I and type II fibers, and the fiber type distribution. ND
      administration did not seem to affect any of those parameters. In the AAS group,
      mean muscle fiber size (+ 12.6%), and the size of type I (+ 10.8%) and type II (+
      14.6%) muscle fibers increased. The fiber type distribution remained unaltered.
      We conclude that polydrug regimens of AAS misuse at supratherapeutic dosages
      increased the size of deltoid muscle fibers (especially type II fibers) in
      experienced strength-trained athletes, while ND at a therapeutic intramuscular
      dose of 200 mg did not exert any effect.

PMID- 11990733
TI  - Endurance enhancement related to the human angiotensin I-converting enzyme I-D
      polymorphism is not due to differences in the cardiorespiratory response to
      training.
AB  - Human physical performance is strongly influenced by genetic factors. We have
      previously reported that the I variant of the human angiotensin I-converting
      enzyme (ACE) gene is associated with greater endurance performance in
      mountaineers and Olympic runners and improved performance in army recruits. In
      this study we examined whether this effect is mediated by improvements in
      cardiovascular fitness with training in 58 army recruits homozygous for the
      insertion (I, ACE genotype II) or deletion (D, ACE genotype DD) allele. A
      submaximal and maximal exercise protocol was used to calculate both the heart
      rate/oxygen uptake (VO2) relationship and changes in maximal oxygen uptake
      (VO2max), respectively. There was no significant intergroup difference in VO2max
      at baseline (P=0.19) or after training (P=0.22). There was no difference between
      genotypes with training in the heart rate/VO2 elevation (P = 0.79 for the mean
      difference in mean adjusted heart rates). However, VO2 at all exercise
      intensities in the submaximal test was lower for all subjects after training and
      at 80 W the reduction in VO2 was greater for the II subjects compared to DD
      subjects [mean(SEM)] [1.6 (0.27) and 0.68 (0.27) ml kg(-1) min(-1), respectively;
      P = 0.02 for mean difference]. The I/D polymorphism may play a role in enhanced
      endurance performance but this is not mediated by differences in VO2max or the
      heart rate/VO2 relationship in response to training.

PMID- 11990734
TI  - Effect of age and pedalling rate on cycling efficiency and internal power in
      humans.
AB  - The present study was undertaken to examine the effect of age and pedalling
      frequency on metabolic internal power (MPint) and delta efficiency (deltaE),
      defined as the ratio of the change in external work accomplished to the change in
      energy expended, during sub-maximal exercise on a cycle ergometer. A group of II
      children [mean age (SD)][10.6 (1.0) years] and 12 adults [23.6 (3.0) years], all
      cyclists, performed two incremental tests at 60 rpm and 90 rpm in a randomised
      order. External power (EP) was measured as the product of friction load and
      pedalling frequency. Oxygen consumption (VO2) was measured using the Douglas bag
      method and an energy equivalent of 20.6 kJ x lO2(-1) was used to convert VO2 into
      metabolic power (MP). Linear relationships were drawn between MP and EP (MP = aEP
      + b) to enable the calculation of deltaE (I/a) and MPint (b). All coefficients of
      determination were greater than 0.97. The results showed that children and adults
      increased their deltaE with the increase in pedalling rate [27 (6)% to 36 (5)%, P
      < 0.05 in children and 27 (3)% to 30 (2)%, P < 0.05 in adults]. Likewise, net
      MPint (MPint minus basal metabolism) expressed relative to total leg volume was
      higher at 90 rpm compared to 60 rpm [16.5 (5.0) W x l(-1) and 4.2 (2.0) W x l(
      1), P<0.05, respectively, in children and 7.4 (3.0) W x l(-1) and 5.0 (2.5) W x
      l(-1), NS, respectively, in adults]. At 60 rpm, children and adults showed the
      same deltaE and net MPint values. At 90 rpm, children showed significantly higher
      deltaE and net MPint compared to adults. This study demonstrated that deltaE and
      net MPint are equally influenced by increasing pedalling rate in children and
      adults. Furthermore, it was hypothesized that differences between children and
      adults at 90 rpm could be related to different anthropometric characteristics.

PMID- 11990735
TI  - Effect of immobilization and retraining on torque-velocity relationship of human
      knee flexor and extensor muscles.
AB  - The effect of 2 weeks immobilization of the uninjured right knee and 10 weeks of
      retraining on muscle torque-velocity characteristics was investigated in nine
      young subjects. Left and right knee extension and flexion maximal voluntary
      isometric torque (Tmax) and dynamic torque at 60 degrees s(-1) (T60) and 180
      degrees x s(-1) (T180) were measured before (PRE) and after immobilization (POST)
      and after 3 (R3) and 10 (R10) weeks of dynamic retraining. The torque-velocity
      relationship was quantified by expressing T60 and T180 relative to Tmax (NT60 and
      NT180, respectively). For the right extensor muscles, percutaneous biopsy samples
      were obtained from the vastus lateralis muscle and fibre type distribution was
      measured. POST extension and flexion torque (mean of Tmax, T60 and T180)
      decreased by 27% and 11%, respectively. During the course of the experiment, the
      changes in NT60 and NT180 were similar. POST extensor muscle NTV (mean of NT60
      and NT180) was decreased significantly (12%, P<0.05), but no significant change
      was found for flexor muscle NTV (+ 3%). At R3 Tmax, dynamic torque and NTV were
      restored to normal. Unlike isometric torque, NTV did not change from R3 to R10.
      No changes in fibre type distribution were found. The adaptation of muscle length
      is suggested as the mechanism to explain the change in NTV.

PMID- 11990736
TI  - Heart rate variability after prolonged spaceflights.
AB  - Astronauts returning from spaceflight often experience post-flight orthostatic
      intolerance. This study was designed to determine whether cosmonauts with post
      flight syncope could be distinguished from those with no post-flight syncope. The
      autonomic function was determined in a group of ten subjects, with no previous
      history of syncope, during a stand test before and after a long-term spaceflight
      (90 to 198 days). Heart rate (HR) and systolic blood pressure (SBP) were measured
      beat-by-beat, pre- and post-flight and the spontaneous baroreflex sensitivity and
      HR variability were studied. Individuals were categorized according to their
      ability to remain standing for 5 min the day after landing. Three of the ten
      cosmonauts failed to finish the standing test performed the day after landing
      (nonfinishers). The spontaneous baroreflex slope was reduced in both groups after
      the spaceflight. The non-finisher group had a lower SBP (P < 0.05) at rest in pre
      flight tests than the group that completed the test (finisher group). The non
      finisher group also had higher indicators of parasympathetic activity when
      supine, both pre- and post-flight, but this difference disappeared with standing.
      At the end of the stand test, SBP and HR were lower in non-finisher cosmonauts
      than the finishers, while HR did not increase compared to early measurements in
      the stand test of the finisher group. These results suggest an impairment in
      autonomic control of HR, which might contribute to the fainting response.

PMID- 11990737
TI  - Influence of acute exercise on human platelet responsiveness: possible
      involvement of exercise-induced oxidative stress.
AB  - The aim of this study was to evaluate in sedentary male subjects the effects of
      an acute bout of strenuous and moderate exercise on ex vivo platelet
      responsiveness and its possible relationship with exercise-associated
      modifications of oxidant-antioxidant status. An increased ADP- and collagen
      evoked platelet aggregation associated with modified membrane fluidity and ion
      homeostasis was observed after exhaustive exercise. After moderate exercise, we
      found a decrease of platelet aggregation evoked by low concentrations of
      agonists. Strenuous exercise, but not moderate exertion, resulted in the enhanced
      accumulation of secondary products of lipid peroxidation, decreased total
      antioxidant capacity, including a diminished superoxide dismutase activity, and
      increased susceptibility of low-density lipoprotein (LDL) to in vitro oxidation.
      Acute elevation of plasma nitrite/nitrate (NOx) content was observed following
      each single session of physical test, whilst the platelet NOx content was
      decreased after strenuous exercise and increased after moderate exercise.
      Findings of the present study suggest that oxidative stress induced by acute
      strenuous exercise may interfere with platelet responsiveness most likely by
      promoting oxidized LDL-mediated platelet activation and by decreasing plasma and
      platelet-derived nitric oxide (NO) bioactivity. Moreover, our results further
      suggest that platelet responsiveness following an acute moderate physical
      stressor may depend on the efficiency of plasma and intraplatelet NO to
      desensitize platelets to agonist stimulation.

PMID- 11990738
TI  - Interaction of blood flow and oxygen delivery affects peak VO2 and fatigue in
      canine muscle in situ.
AB  - This investigation was designed to examine the interactive effects of blood flow
      (Q) and oxygen delivery (QO2) on peak oxygen consumption (VO2peak) and fatigue in
      the gastrocnemius-plantaris dog muscle in situ. Arterial oxygen content (CaO2)
      was manipulated by varying the fraction of inspired O2 to create a high- and a
      low-QO2 treatment at each of three levels of Q (approximately/=800, 1100 and 1500
      ml x kg(-1) x min(-1)). Isometric contraction was achieved by stimulation with
      one tetanic contraction per second (200 ms at 70 Hz) at supramaximal voltage for
      10 min to achieve VO2peak under each condition. Arterial and venous blood were
      sampled, and Q and tension development (TD) were measured at 1, 5 and 10 min into
      the contractions. Fatigue was calculated as the percentage (%) change in TD from
      min 1 to min 10. While VO2peak was highly correlated to QO2 (R = 0.97) in both
      the moderate- and high-Q conditions, both low-Q conditions had a significantly (P
      < 0.05) higher VO2peak than predicted by the QO2-VO2 relationship. In addition,
      VO2 peak was significantly greater in the low-Q versus the high-Q condition.
      Fatigue (% decrease in TD) was significantly different between the two low-Q
      conditions [Low-QO2=38.4 (6.9); Norm QO2=27.9 (1.8)] and the two moderate-Q
      conditions [low-QO2=31.1 (7.3); high-QO2 = 20.9 (4.1)] but not between the two
      high-Q conditions [normal-QO2 = 10.4 (6.9); high-QO2 = 11.9 (4.5)]. In the two
      conditions of equal QO2, fatigue was significantly less in the high-Q condition
      (10.4%) compared to the low (27.9%). Thus, it seems that there is a unique
      interaction between Q and QO2 which determine the VO2peak and rate of fatigue in
      contracting muscle.

PMID- 11990739
TI  - Metabolic response to light exercise after exercise-induced rhabdomyolysis.
AB  - Inherent compromises in substrate metabolism, or impaired perfusion of muscle may
      contribute to the occurrence of exercise-induced rhabdomyolysis. In this study,
      the lactate response of the elbow flexor muscles to light exercise was examined
      in eight subjects (five males, three females) who previously demonstrated
      rhabdomyolysis with extreme swelling (ES; n = 4) or no swelling (NS; n = 4) of
      the upper arm after eccentric exercise. Subjects performed identical light
      exercise bouts (45 s of rapid isotonic biceps curls consisting of both concentric
      and eccentric actions at 25% of maximum voluntary contraction force) using their
      previously eccentrically exercised arm (E-ARM) and control arm, which was not
      used previously to perform eccentric exercise (C-ARM). Blood lactate
      concentration ([La]b) was assessed 1.5, 3, 4.5, 6, and 9 min post-exercise. Peak
      [La]b and the area under the curve (AUC) were compared between the E-ARM of the
      ES and NS groups and between the C-ARM and E-ARM of the ES group. The AUC did not
      differ between the E-ARM of the ES and NS groups (P > 0.05) or between the C-ARM
      and E-ARM of the ES group (P > 0.05). In the ES group, the increase in [La]b
      after light exercise with the C-ARM [mean (SD) change, delta: 1.98 (0.7) mmol/l]
      was not different from the increase after exercising the E-ARM [delta: 2.10 (0.7)
      mmol/l; P>0.05]. Comparing the response of the E-ARM between groups, the increase
      in [La]b of the NS group [delta: 1.40 (0.4) mmol/l] was not different than that
      observed in the ES group [delta: 2.10 (0.7) mmol/l; P>0.05). Thus, subjects who
      had previously exhibited signs of exercise-induced rhabdomyolysis did not show an
      abnormal response to low-intensity anaerobic exercise.

PMID- 11990740
TI  - Quantitation of muscle oxygenation by near-infrared spectroscopy methods.

PMID- 11990741
TI  - Cross education of muscular strength during unilateral resistance training and
      detraining.
AB  - The purpose of the present study was to examine the changes in maximum voluntary
      isometric contraction (MVC) in the contralateral untrained limb during unilateral
      resistance training and detraining, and to examine the factors inducing these
      changes by means of electrophysiological techniques. Nine healthy males trained
      their plantar flexor muscles unilaterally 4 day-s x week(-1) for 6 weeks using 3
      sets of 10-12 repetitions at 70-75% of one-repetition maximum a day, and
      detrained for 6 weeks. Progressive unilateral resistance training significantly
      (P < 0.05) increased MVC, integrated electromyogram (iEMG), and voluntary
      activation in the trained and contralateral untrained limbs. The changes in MVC
      after training were significantly correlated with the changes in iEMG in both
      limbs. No significant changes occurred in MVC, voluntary activation, and iEMG in
      the contralateral limb after detraining. The changes in MVC after detraining did
      not correlate with the changes in voluntary activation or iEMG in either limb.
      Training and detraining did not alter twitch and tetanic peak torques in either
      limb. These results suggest that the mechanisms underlying cross education of
      muscular strength may be explained by central neural factors during training, but
      not solely so during detraining.

PMID- 11990742
TI  - Spreading of fatigue-related effects from active to inactive parts in the medial
      gastrocnemius muscle of the cat.
AB  - In the medial gastrocnemius muscle of the decerebrate cat, the spatial spread of
      fatigue between active and inactive muscle parts was studied. Conditioning
      fatiguing stimulation (CFS) was applied to a part of the muscle to test whether
      it had an effect on the contraction efficiency in an unstimulated part. To
      exclude somato-sympathetic reflexes during CFS, a full rhizotomy of the lumbo
      sacral spinal cord was performed. The same ipsilateral ventral root, either L7 or
      S1, was divided into seven filaments, one of which was used for the test
      stimulation, and four or five for CFS. The CFS consisted of 12 s sessions of
      distributed stimulation of five (or four) filaments at a rate of 40 s(-1), the
      sessions were repeated, every 40 s, 15 or more times. The test consisted of 12 s
      of regular stimulation at a rate of 10 s(-1), preceded and followed by a single
      stimulus. The tests applied just after CFS showed a strong decline of both
      tension and electromyogram (EMG), amounting to only [mean (SD)] 0.45 (0.18) and
      0.51 (0.19) (n = 15), respectively, of the corresponding values in the tests
      before CFS. It thus turned out that depressive fatigue-related effects could
      spread within the muscle. At the same time, control reactions recorded in the
      lateral gastrocnemius during stimulation of its cut nerve did not change.
      Subsequent repetitions of the tests usually revealed a tendency towards
      restoration. The EMG reactions recovered more quickly than tension. The
      depression of EMG after CFS was accompanied by a slowing of the constituent M
      waves; their latencies decreased during restoration. Distinct changes in the
      systemic blood pressure were observed during CFS. These changes were usually
      correlated well with muscle tension changes. The factors possibly underlying the
      observed effects may include diffusion of metabolites from active to inactive
      muscle fibres, lowering of the efficiency of neuro-muscular transmission due to
      squeezing of efferent motor terminals and changes in outer metabolite content, as
      well as local hypoxia due to increases in intramuscular pressure.

PMID- 11990743
TI  - Effects of resistance exercise combined with vascular occlusion on muscle
      function in athletes.
AB  - The effects of resistance exercise combined with vascular occlusion on muscle
      function were investigated in highly trained athletes. Elite rugby players (n =
      17) took part in an 8 week study of exercise training of the knee extensor
      muscles, in which low-intensity [about 50% of one repetition maximum] exercise
      combined with an occlusion pressure of about 200 mmHg (LIO, n = 6), low-intensity
      exercise without the occlusion (LI, n = 6), and no exercise training (untrained
      control, n = 5) were included. The exercise in the LI group was of the same
      intensity and amount as in the LIO group. The LIO group showed a significantly
      larger increase in isokinetic knee extension torque than that in the other two
      groups (P < 0.05) at all the velocities studied. On the other hand, no
      significant difference was seen between LI and the control group. In the LIO
      group, the cross-sectional area of knee extensors increased significantly (P <
      0.01), suggesting that the increase in knee extension strength was mainly caused
      by muscle hypertrophy. The dynamic endurance of knee extensors estimated from the
      decreases in mechanical work production and peak force after 50 repeated
      concentric contractions was also improved after LIO, whereas no significant
      change was observed in the LI and control groups. The results indicated that low
      intensity resistance exercise causes, in almost fully trained athletes, increases
      in muscle size, strength and endurance, when combined with vascular occlusion.

PMID- 11990744
TI  - Effects of resistance exercise volume and nutritional supplementation on anabolic
      and catabolic hormones.
AB  - Seven resistance-trained men performed six bouts of resistance exercise, each
      separated by at least 1 week, in a crossover design. High, moderate and low
      volumes of exercise were used, each performed twice and followed immediately post
      exercise by either a placebo or carbohydrate-protein supplementation. All bouts
      of resistance exercise were performed using a load equal to 100% of each
      subject's ten-repetition maximum (10-RM), and all rest periods between sets of
      exercise were 1 min. Blood was obtained before and at intervals after exercise
      until 120 min post-exercise. Lactate levels were significantly (P < 0.05)
      elevated immediately post-exercise, and to a significantly greater extent after
      the greatest volume of exercise. Levels of growth hormone rose significantly
      after the greatest volume of exercise only. Those of insulin and glucose rose
      significantly after supplementation only. Cortisol levels tended to be higher
      after the greatest volume of exercise, but the differences were not significant.
      Supplementation had no effect on the lactate, growth hormone or cortisol
      responses to resistance exercise. The data indicate that volume of exercise and
      protein-carbohydrate supplementation can alter the metabolic and hormonal
      responses to resistance exercise independently. However, cortisol levels remain
      high after a high volume of resistance exercise, irrespective of whether a post
      exercise carbohydrate-protein supplement is used.

PMID- 11990745
TI  - Postural ataxia at high altitude is not related to mild to moderate acute
      mountain sickness.
AB  - To evaluate the role of acute mountain sickness (AMS) in the pathogenesis of
      stance abnormalities occurring at high altitude, static posturography was applied
      to 22 healthy subjects at an altitude of 450 m and during a 3-day sojourn at 4559
      m. Subjects stood on a platform and sway velocity (S), and sway velocity in the
      antero-posterior (S(AP)) and medio-lateral (S(ML)) directions was recorded for 20
      s with eyes open (EO) and 20 s with eyes closed (EC). Arterialized blood from an
      ear lobe was analyzed to determine the arterial partial pressures of oxygen
      (PaO2) and carbon dioxide, and oxygen saturation (SaO2). AMS was assessed by the
      environmental symptom questionnaire (ESQ) of Sampson (cerebral AMS, AMS-C score >
      0.7). AMS affected four subjects on day 1, ten subjects on day 2, and five
      subjects on day 3. Posturographic findings showed no difference between subjects
      with AMS and healthy subjects, and no correlation with the ESQ score. PaO2 and
      SaO2 showed non-significant trends toward lower values in subjects with AMS than
      in those without AMS. Posturographic parameters significantly worsened on the 1st
      (EO-S, P < 0.001; EC-S, P < 0.01; EO-SML, P < 0.05), 2nd (EO-S, EC-S and EO-SML,
      P < 0.01) and 3rd days (EC-S, P < 0.05) at high compared to low altitude.
      Differences in AMS-C score, SaO2 and PaO2 were significant between low and high
      altitude (P < 0.0001). Our data suggest that AMS is not important in the
      pathogenesis of postural ataxia occurring at high altitude.

PMID- 11990746
TI  - The role of FFM accumulation and skeletal muscle architecture in powerlifting
      performance.
AB  - The purpose of this study was to determine the distribution and architectural
      characteristics of skeletal muscle in elite powerlifters, and to investigate
      their relationship to fat-free mat (FFM) accumulation and powerlifting
      performance. Twenty elite male powerlifters (including four world and three US
      national champions) volunteered for this study. FFM, skeletal muscle distribution
      (muscle thickness at 13 anatomical sites), and isolated muscle thickness and
      fascicle pennation angle (PAN) of the triceps long-head (TL), vastus lateralis,
      and gastrocnemius medialis (MG) muscles were measured with B-mode ultrasound.
      Fascicle length (FAL) was calculated. Best lifting performance in the bench press
      (BP), squat lift (SQT), and dead lift (DL) was recorded from competition
      performance. Significant correlations (P < or = 0.01) were observed between
      muscle distribution (individual muscle thickness from 13 sites) and performance
      of the SQT (r = 0.79 to r = 0.91), BP (r = 0.63 to r = 0.85) and DL (r = 0.70 to
      r = 0.90). Subscapular muscle thickness was the single best predictor of
      powerlifting performance in each lift. Performance of the SQT, BP, and DL was
      strongly correlated with FFM and FFM relative to standing height (r = 0.86 to
      0.95, P < or = 0.001). FAL of the triceps long head and vastus lateralis were
      significantly correlated with FFM (r = 0.59, P < or = 0.01; 0.63, P < or = 0.01,
      respectively) and performance of the SQT (r = 0.45; r = 0.50, respectively; P <
      or = 0.05), BP (r = 0.52; r = 0.56, respectively; P < or = 0.05), and DL (r =
      0.56; r = 0.54, respectively; P < or = 0.01). A significant positive correlation
      was observed between isolated muscle thickness and PAN for triceps long-head (r =
      0.64, P < or = 0.01) and gastrocnemius medialis (r = 0.48, P < or = 0.05)
      muscles, but not for vastus lateralis (r = 0.35). PAN was negatively correlated
      with powerlifting performance. Our results indicate that powerlifting performance
      is a function of FFM and, therefore, may be limited by the ability to accumulate
      FFM. Additionally, muscle architecture appears to play an important role in
      powerlifting performance in that greater fascicle lengths are associated with
      greater FFM accumulation and powerlifting performance.

PMID- 11990747
TI  - Influence of 2D and 3D body segment models on energy calculations during
      kinematic analysis of running.
AB  - The aims of the present study were: (1) to examine the influence of two
      dimensional (2D) and three-dimensional (3D) analysis on the body's total energy
      during the support phase of running, and (2) to examine the influence of the
      choice of anthropometric models on the body's total energy during running. A
      total of 14 runners participated in the investigation [mean (SD) height: 1.83
      (0.03) m, body mass: 79.67 (5.65) kg]. Two genlocked high-speed cameras (120 Hz)
      filmed each athlete's movement during single-foot ground contact. The exact
      support time of the athletes was measured with a Kistler force plate (sampling
      frequency: 1000 Hz). The masses and moments of inertia of the various segments
      were estimated using the 2D and 3D models of Hanavan (1964) as well as the 3D
      model of Zatsiorsky et al. (1984). The influence of the 2D and 3D analysis on the
      calculations was evaluated by comparing of the total energies calculated using
      Hanavan's 2D and 3D models. The influence of the choice of the anthropometric
      model on the calculations was checked by comparing the results obtained using the
      Hanavan 3D model and those obtained using the 3D model of Zatsiorsky et al.
      (1984). The data show us that 2D and 3D analyses produce similar energy values
      during the entire support phase of running (only very small percentage energy
      differences were observed: e.g. from 0.23% for the energy of the body at the
      first contact with the ground, up to 0.31% for the energy of the body at the time
      the athlete leaves the ground, E(TO)). In addition, calculations made using the
      3D models of Hanavan and Zatsiorsky also produced similar results for energy
      values (energy differences from 0.33% for energy minimum, up to 0.8% for E(TO)).
      It can be assumed, therefore, that neither the choice of the anthropometric model
      nor the calculations made on the basis of 3D coordinates are limiting factors in
      the calculation of body total energies for running.

PMID- 11990748
TI  - The effect of exercise intensity on the post-exercise esophageal temperature
      response.
AB  - On 2 separate days, nine volunteers aged 23.8 (2.0) years performed 15-min bouts
      of treadmill running in a temperature-controlled chamber at 29 degrees C at a
      power output that elicited either 70% (moderate) or 93% (intense) of maximum
      oxygen consumption. Exercise was followed by a 45-min recovery period. End
      exercise esophageal temperature (Tes) was elevated by 0.97 degrees C and 2.17
      degrees C above baseline for the moderate and intense exercise trials,
      respectively. Post-exercise Tes achieved a sustained elevated value of 0.38
      degrees C and 0.79 degrees C within 15 min of exercise cessation. Systolic blood
      pressure (SBP) for both exercise trials became hypotensive for the full recovery
      period, with the magnitude of the reduction being greater for the intense
      exercise (P < 0.05). Diastolic blood pressure (DBP) was unaffected by exercise
      intensity and values were lower than baseline between 15 min and 30 min post
      exercise (P < 0.05). Mean arterial pressure (MAP) was reduced from baseline for
      both exercise trials, with intense exercise showing a greater decrement (P <
      0.05). It was shown that the increase in the post-exercise hypotensive response,
      induced by exercise of increasing intensity, was paralleled by an increase in the
      magnitude of the post-exercise elevation in Tes (i.e., a difference of 0.41
      degrees C between conditions).

PMID- 11990749
TI  - Oxygen uptake kinetics during treadmill running across exercise intensity
      domains.
AB  - The purpose of the present study was to examine comprehensively the kinetics of
      oxygen uptake (VO2) during treadmill running across the moderate, heavy and
      severe exercise intensity domains. Nine subjects [mean (SD age, 27 (7) years;
      mass, 69.8 (9.0) kg; maximum VO2, VO2max, 4,137 (697) ml x min(-1)] performed a
      series of "square-wave" rest-to-exercise transitions of 6 min duration at running
      speeds equivalent to 80% and 100% of the VO2 at lactate threshold (LT; moderate
      exercise); and at 20%, 40%, 60%, 80% and 100% of the difference between the VO2
      at LT and VO2max (delta heavy and severe exercise). Critical velocity (CV) was
      also determined using four maximal treadmill runs designed to result in
      exhaustion in 2-15 min. The VO2 response was modelled using non-linear regression
      techniques. As expected, the amplitude of the VO2 primary component increased
      with exercise intensity [from 1,868 (136) ml x min-( 1) at 80% LT to 3,296 (218)
      ml x min-(1) at 100% delta, P < 0.05]. However, there was a non-significant trend
      for the "gain" of the primary component to decrease as exercise intensity
      increased [181 (7) ml x kg(-1) x km(-1) at 80% LT to 160 (6) ml x kg(-1) x km(-1)
      at 100% delta]. The time constant of the primary component was not different
      between supra-LT running speeds (mean value range = 17.9-19.1 s), but was
      significantly shorter during the 80% LT trial [12.7 (1.4) s, P < 0 .05]. The VO2
      slow component increased with exercise intensity from 139 (39) ml x min(-1) at
      20% delta to 487 (57) ml x min(-1) at 80% delta (P < 0.05), but decreased to 317
      (84) ml x min(-1) during the 100% delta trial (P < 0.05). During both the 80%
      delta and 100% delta trials, the VO2 at the end of exercise reached VOmax [4,152
      (242) ml x min(-1) and 4,154 (114) ml x min(-1), respectively]. Our results
      suggest that the "gain" of the primary component is not constant as exercise
      intensity increases across the moderate, heavy and severe domains of treadmill
      running. These intensity-dependent changes in the amplitudes and kinetics of the
      VO2 response profiles may be associated with the changing patterns of muscle
      fibre recruitment that occur as exercise intensity increases.

PMID- 11990750
TI  - The effect of preload on variability in dynamometric measurements of knee
      extension.
AB  - The unwanted variability in dynamometric measurements limits accurate
      interpretation of these measurements. Although unpredictable variability in
      measurements has been identified repeatedly, few studies have investigated
      strategies for reducing measurement error. This study investigated the effect of
      preload on variability in dynamometry. Preload is the force that must be overcome
      before the lever arm begins to move at a preset speed. On the basis of related
      research, it was hypothesised that under higher preloads, subjects would perform
      more consistently. Twenty subjects (ten male and ten female), aged 19-24 years,
      performed repeated right concentric knee extension tests. Using the Kin-Com
      dynamometer and a lever arm speed of 60 degrees x s(-1), extension torques were
      recorded for each subject under four different preload conditions. Preloads were
      5%, 25%, 45% and 65% of the torque achieved during each subject's maximal
      voluntary contraction (MVC). Each subject performed six test repetitions under
      each preload. Variability in peak torque was significantly smaller under the 65%
      preload compared to the 5% preload. In addition, the regression of preload
      against group mean variability indicated that as preload increased, the
      variability in peak torque decreased in a highly predictable way. The results
      from this study suggest that subjects perform more consistently under conditions
      of higher preload than under lower preloads. By adopting higher preloads for
      dynamometry testing, measurement accuracy and the potential clinical utility of
      measurements is improved.

PMID- 11990751
TI  - On the mechanical power of joint extensions as affected by the change in muscle
      force (or cross-sectional area), ceteris paribus.
AB  - This paper offers a reference prediction for the changes of mechanical power
      generated during a maximal (vertical, horizontal or inclined) joint extension, as
      a consequence of just the changes of muscle force or cross-sectional area (CSA).
      Ceteris paribus (all other things being equal), for a given joint, the exponents
      at which the force changes have to be raised to predict the duration, final speed
      and power of the maximal extension are -0.5, 0.5, and 1.5, respectively, for
      horizontal movements. For example, a force decrease of 30% leads to an increase
      of 19.5% of the duration of the extension and to a decrease of 16.3% and of 41.4%
      of its final speed and power. The equations for vertical or inclined extension
      performances are subject to the same exponents. However, the actual prediction is
      dependent upon the ratio between muscle strength and body weight, reflecting the
      fraction of the muscle strength (or CSA) acting against gravity during the
      manoeuvre. For instance, during a vertical extension, a force decrease of 30%
      leads to an increase of 30.9% of the duration of the extension and to a decrease
      of 29.3% and of 50.5% of its final speed and power. Based on the proposed model,
      a methodology is also described to detect the effects on the extension power of
      other determinants, in addition to CSA, of the useful force change (e.g.
      neuromuscular factors, motor control).

PMID- 11990752
TI  - High intensity exercise cycle ergometer performance: the influence of handgrip
      and resistive force selection.

PMID- 11990753
TI  - Construction of a BAC contig for a 3 cM biologically significant region of mouse
      chromosome 1.
AB  - One QTL and genes and phenotypes have been localized in the region between 92 cM
      and 95cM of mouse chromosome 1. The QTL locus contributes to approximately 40% of
      the variation of the peak bone density between C57BL/6J (B6) and CAST/EiJ (CAST)
      strains. Other loci located in this chromosomal region include a neural tube
      defect mutant loop-tail (Lp), a lymphocyte-stimulating determinant (Lsd), and the
      Transgelin 2 (Tagln 2). The human chromosome region homologous to this region is
      1q21-23, which also contains a QTL locus for high bone mineral density (BMD).
      Furthermore, it has been reported that this region may have duplicated several
      times in the mouse genome. Therefore, genomic sequencing of this region will
      provide important information for mouse genome structure, for positional cloning
      of mouse genes, and for the study of human homologous genes. In order to provide
      a suitable template for genomic sequencing by the NIH-sponsored genomic centers,
      we have constructed a BAC contig of this region using the RPCI-23 library. We
      have also identified the currently available mouse genomic sequences localized in
      our BAC contig. Further analysis of these sequences and BAC clones indicated a
      high frequency of repetitive sequences within this chromosomal area. This region
      also contains L1 retrotransposon sequences, providing a potential mechanism for
      the repetitive sequences described in the literature.

PMID- 11990754
TI  - (T2AG3)n telomeric sequence hybridization indicating centric fusion
      rearrangements in the karyotype of the rodent oryzomys subflavus.
AB  - Chromosome preparations of 30 specimens of Oryzomys subflavus trapped in eight
      Brazilian localities were C-, and G-banded and analyzed by fluorescence in situ
      hybridization (FISH). Two karyotypes were found, 2n = 50/FN = 64, at three
      coastal localities of the Atlantic Forest domain, and 2n = 58/FN = 70 at two
      sites located in the Cerrado biome, Brazil Central. Two fluorescence in situ
      hybridization (FISH) patterns of the telomeric sequence (T2AG3)n were observed:
      in both karyotypes the probes hybridized to the telomeres of all chromosomes and
      also a hybridization signal in the centromeric regions of two autosome pairs was
      seen in the 2n = 50 karyotype. These results, together with the occurrence of
      other diploid numbers described in the literature, suggest that 0. subflavus is a
      complex species, bearing fusion/fission rearrangements proper to the different
      biomes which it inhabits.

PMID- 11990755
TI  - Testing two possible mechanisms for gametic association in human: frozen
      haplotypes and segregation distortion.
AB  - Two possible mechanisms for the development and maintenance of gametic
      association have been subject to test using family studies (HLA typed) and direct
      analysis of two linked markers in individual sperm. The mechanisms are: (I)
      haplotypes frozen against recombination and (2) balanced segregation distortion.
      In the study of 1,320 families, 86 individuals were identified in the offspring
      of whom recombination was confirmed or suspected. These individuals displayed
      allele frequencies of HLA similar to the others in the study, but had
      significantly different haplotype frequencies. In general, they displayed reduced
      (or absent) frequencies for the more common haplotypes. Similarly, in the study
      of meiotic products, recombination was observed in the individual whose HLA
      phenotypes suggested rare haplotypes, but not in the other individual. Both
      results were of marginal significance. When the family data were used to test for
      segregation distortion at HLA-DR, only a marginally significant result was found.
      However, when the data were classified according to the sex of the parent, a
      highly significant result was found in females, but not in males. Male
      segregation distortion was found in the sperm analysis, but was only of marginal
      statistical significance. The concordant results of two different experimental
      systems suggest that both mechanisms remain feasible explanations of the gametic
      associations in this area of the genome, although of the two, segregation
      distortion is preferable on theoretical grounds.

PMID- 11990756
TI  - Inversion polymorphisms in populations of Drosophila melanogaster in the South
      West islands of Japan: comparisons with the mainland populations.
AB  - Natural populations of D. melanogaster newly collected from the South-West
      Islands of Japan were examined for the frequencies of inversions, and the
      results, together with previous data, were compared with those of the mainland
      populations. The four Common cosmopolitan inversions (2Lt, 2RNS, 3LP, 3RP) were
      detected from most of the populations with higher frequencies. The three Rare
      cosmopolitan inversions (3LM, 3RC, 3RMo), three Quasi cosmopolitan inversions
      (2LA, 3LY, 3RK) and two new Endemic inversions were also found but with lower
      frequencies. Some of the South-West Island populations still maintained higher
      levels of inversion polymorphisms compared to the mainland populations, while
      others lost the polymorphisms to various degrees. The South-West Island
      populations were characterized by the higher frequency of In(3L)P. The ratios of
      In(3L)P /In(3R)P in the South-West Islands are significantly higher than those of
      the mainland populations, suggesting that the In(3L)P is relatively adaptive in
      the South-West Islands.

PMID- 11990757
TI  - Chiasma repatterning across a chromosomal hybrid zone between chromosomal races
      of Mus musculus domesticus.
AB  - Chiasma number and distribution were analysed in male house mice from a
      karyotypic hybrid zone between the CD race (2n = 22) and the standard race (2n =
      40) located in central Italy. Chiasma repatterning occurs across the transect.
      The overall trend produces a diminution of chiasmata in the mice with CD
      chromosomal background. The progressive reduction of chiasmata indicates that
      genes could pass from one race to another in an asymmetrical way: from
      metacentric races to the standard population.

PMID- 11990758
TI  - Esterase patterns and phylogenetic relationships of Drosophila species in the
      saltans subgroup (saltans group).
AB  - The esterase patterns of sixteen strains from four species in the saltans
      subgroup were analyzed using polyacrylamide gel electrophoresis. Thirty-four
      esterase bands were detected. By using alpha and beta naphthyl acetates as
      substrates, they were classified in 18 alpha-esterases (they hydrolyse the alpha
      naphtyl substrate), 15 beta-esterases (they hydrolyse the beta-naphtyl substrate)
      and 1 alpha/beta-esterase (it hydrolyses the alpha and beta-naphtyl substrates).
      Among the alpha-esterases, three were detected exclusively in males. Malathion,
      Eserine and pCMB were used as inhibitors in order to characterize biochemically
      the esterases. The results indicated the presence of cholinesterases,
      carboxylesterases and acetylesterases. The degree of mobility of the bands in the
      gels, their specificity to alpha and beta naphthyl acetates and the results of
      the inhibition tests allowed us to recognize tentatively nine genetic loci.
      Phylogenetic relationships among species inferred on the basis of the esterase
      patterns by PAUP 4.0b8, with neighbor-joining search and a bootstrap analysis
      showed that, although the four species are closely related, D. septentriosaltans,
      D. saltans and D. austrosaltans are closer to each other than to D. prosaltans.
      These results showed to be consistent with phylogenetic relationships previously
      inferred from inversion polymorphism.

PMID- 11990759
TI  - Synaptonemal complex analysis in oocytes and spermatocytes of threespine
      stickleback Gasterosteus aculeatus (Teleostei, Gasterosteidae).
AB  - A surface-spreading synaptonemal complex (SC) technique was employed to analyze
      spermatocytes and oocytes of stickleback, Gasterosteus aculeatus, in order to
      visualize the process of chromosome synapsis. The mean SC length was 150 +/- 18
      microm in three males and 143 +/- 12 microm in one female analyzed. A
      representative SC karyotype with 21 bivalents was also presented. Each SC had
      lateral elements of equal length. No bivalent displaying the atypical synaptic
      behaviour which is often associated with heteromorphic sex chromosomes was
      observed neither in males nor in the female analyzed.

PMID- 11990760
TI  - NOR sites detected by Ag-dAPI staining of an unusual autosome chromosome of
      Bradysia hygida (Diptera:Sciaridae) colocalize with C-banded heterochromatic
      region.
AB  - The study of chromosomes in insects is a good tool in mitotic process analysis,
      zoographic localization and evolution investigation. Among them, the Sciaridae
      offers a karyotype with a small number of chromosomes, where the heterochromatin
      and nucleolar organizer region, NOR, are easily analyzed in metaphase chromosomes
      obtained from cerebral ganglia squashes. In this work, the heterochromatic
      regions on Bradysia hygida mitotic chromosomes, revealed by C-banding, were
      identified as centromeric blocks on A and C chromosomes and as dark interstitial
      region in B and X chromosomes. By Ag-DAPI staining, active nucleolus organizer
      region, NOR, was revealed associated to the constitutive heterochromatin in the
      end of the C autosome chromosome. The C-band regions and the unusual ribosomal
      site localization are discussed.

PMID- 11990761
TI  - Gene flow among Calomys musculinus (Rodentia, Muridae) populations in Argentina.
AB  - Calomys musculinus is a Sigmodontinae rodent inhabiting periodically disturbed
      habitats in the central eastern plains of Argentina. It is the natural reservoir
      host of Junin virus, the etiological agent of Argentine Hemorrhagic Fever (AHF).
      In order to analyze the levels of gene flow among populations of this species,
      allozymic variability at 26 loci was studied in 291 individuals from the endemic
      zone of AHF and localities outside it. All populations showed high levels of
      polymorphism (He between 0.107 and 0.144; P95% between 38 and 54%). Individual
      loci f values were in most cases negative, although not significantly different
      from zero. Mean genetic differentiation among populations was low, but
      statistically significant (theta = 0.020; P < 0.01). There was no correlation
      between genetic and geographic distances between pairs of populations, and
      scatter of the pairwise points suggests that, at the regional scale, genetic
      drift is more influential than gene flow. This result can be interpreted as
      indicative of a relatively recent expansion of C. musculinus habitat and
      restricted on-going gene flow, which would be compatible with a relatively slow
      expansion rate of AHF.

PMID- 11990762
TI  - In situ hybridisation analysis of the X-linked genes in the species of the
      virilis group of Drosophila.
AB  - When estimating the level of DNA sequence variation within and between
      populations or when planning QTL analysis, it is essential to know the location
      of the genes under study. In the present work, five X chromosomal genes, earlier
      localised in Drosophila virilis and D. littoralis, were mapped by in situ
      hybridisation on the larval polytene chromosomes of four other virilis group
      species, D. a. americana, D. flavomontana, D. lacicola and D. montana.
      Conjugation of X chromosomes of the most interesting species pairs was studied in
      interspecific hybrids. Three of the marker genes were used as RFLP markers to
      examine the occurrence of recombination in D. flavontontana and D. montana hybrid
      females. The gene arrangement of all species studied, appeared to be different at
      the proximal end of the X chromosome, which prevented normal conjugation along
      the most part of the X chromosome. The data illustrating the locations of five X
      chromosomal marker genes are presented for D. a. americana, D. flavomontana, D.
      lacicola and D. montana.

PMID- 11990763
TI  - Hordein variation and reaction to powdery mildew in composite cross XLII of
      barley.
AB  - A bulk hybrid population, CCXLII was investigated for hordein variation and
      reaction to powdery mildew. The results indicated that the population in F4 was
      genetically variable and contained an appreciable proportion of heterozygotes.
      Evidence was found for differential viability within families. This was possibly
      the result of a high segregation load. The pattern of genetic variation suggests
      that although the population could be a useful source of breeding material for
      the selection of new lines, it may be risky as a method of conservation of
      germplasm.

PMID- 11990764
TI  - The effect of W chromosome origin on sex-chromosome pairing in ZZWW tetraploid
      females of the domesticated silkworm, Bombyx mori, and the congenic wild
      silkworm, Bombyx mandarina.
AB  - To analyze the degree of pairing of the Z and W chromosomes in ZZWW tetraploid
      female silkworms that have the W chromosomes of the domesticated silkworm, Bombyx
      mori, and those of the wild silkworm, Bobyx mandarina, we induced two types of
      ZZWW tetraploid female silkworms (Cr4n, Wr4n) through cold treatment of the eggs.
      The Wr4n female is congenic to the Cr4n female for W chromosomes; namely, the W
      chromosomes of the Wr4n female are derived from those of B. mandarina. Each of
      the sex ratios (female/male) in filial triploids from the Cr4n females was shown
      to be in the range of 3.9-5.3 (4.6 as an average of six cases). On the other
      hand, each of the sex ratios (female/male) in filial triploids from the Wr4n
      females was shown to be in the range of 6.2-9.0 (6.9 as an average of nine
      cases). The results of a t-test indicated that the difference in sex ratios in
      the two groups is highly significant (at the 0.1% level). These results suggest
      that, in the meiosis of the ZZWW tetraploid female, the frequency of pairing of
      the W chromosome of B. mandarina and the Z chromosome of B. mori is lower than
      that of the pairing of the W and Z chromosomes of B. mori. Furthermore, the t
      test results are evidence that the W chromosomes have undergone significant
      evolutional change.

PMID- 11990765
TI  - Effect of temperature on longevity and productivity in Drosophila ananassae:
      evidence for adaptive plasticity and trade-off between longevity and
      productivity.
AB  - The genetic response of body size to temperature in the laboratory provides an
      interesting example of phenotypic plasticity. We found that females of Drosophila
      ananassae reared to adulthood at 18 degrees C showed significant increase in body
      weight as compared to females reared at 25 degrees C. At a given temperature,
      early productivity and lifetime productivity were the highest when the rearing
      and test temperature were the same. The effect of test temperature was highly
      significant for total productivity and early productivity. The interaction
      between test temperature and development temperature was also highly significant.
      Effect of development temperature was not significant. The females reared at 18
      degrees C showed greater body weight but their productivity was not significantly
      higher than smaller females reared at 25 degrees C. Thus, the usually close
      relationship between size and fecundity is lost when the size change is due to
      rearing temperature. These findings provide evidence for adaptive plasticity in
      D. ananassae. We also found a negative correlation (trade-off) between longevity
      and productivity, the first report of such a trade-off between longevity and
      productivity in D. ananassae.

PMID- 11990766
TI  - Hazard assessment of resmethrin: I. Effects and fate in aquatic systems.
AB  - A comparative aquatic hazard assessment of resmethrin was conducted to
      investigate the need for its restricted use classification by the US. EPA as an
      adult mosquito control agent. This paper describes the environmental fate and
      aquatic toxicity of resmethrin. The following paper compares resmethrin to the
      alternative insecticides. Environmental fate studies indicate that resmethrin has
      a short photolytic half-life in water (<1 h). Furthermore, it is immobile in soil
      and biodegradable (half-life = 36.5 d) under aerobic conditions. Laboratory
      studies with constant 48- to 96-h exposures show it is acutely toxic to fish and
      invertebrates in the 0.22-15.0 microg/L range. Daphnia magna, pink shrimp
      (Penaeus duorarum) and rainbow trout (Oncorhynchus mykiss) are the most sensitive
      and mollusks are the least sensitive species. Chronic laboratory studies indicate
      that the maximum acceptable toxicant concentrations (MATCs) for resmethrin and D.
      magna, Pimephales promelas, O. mykiss, and Cyprinodon variegatus are 0.58, 0.52,
      0.43, and 10.3 microg/L, respectively. The acute-to-chronic ratios (1.1-7.3) for
      all species studied indicate that chronic toxicity will not be an issue for
      resmethrin. Furthermore, the characteristics of acute exposures (48- to 96-h)
      used in the laboratory will not occur under field conditions because of the short
      half-life of resmethrin in fresh- and salt-water.

PMID- 11990767
TI  - Effects of sludge filtrate on the survival and reproduction of Ceriodaphnia
      dubia.
AB  - The objective of this study was to determine if the runoff from croplands
      fertilized with municipal sludge was toxic to aquatic biota and, therefore, a
      potential threat to either public health or the environment. Seven-day bioassays
      with Ceriodaphnia dubia showed that the No-Observed-Effect-Concentration (NOEC)
      was 24 g/L and the Lowest-Observed-Effect-Concentration (LOEC) for survival was
      30 g/L for soil samples treated with 35.2 metric tonnes (MT)/ha of municipal
      sludge. For soil samples treated with 0 and 17.6 MT/ha of sludge, the survival
      rates of C. dubia were not significantly affected at concentrations of 6-30 g/L
      of soil. Reproduction was suppressed by 25% when daphnids were exposed to 3.3 g/L
      concentration of soil treated with sludge at 35.2 MT/ha. A 50% suppression of
      reproduction occurred when daphnids were exposed to 15 g/L concentration of soil
      treated with sludge at 17.6 MT/ha. A sludge application rate of 17.6 MT/ha
      suppressed reproduction at a treatment concentration of 18 g/L. These data
      indicate that the runoff from agricultural lands treated with municipal sludge
      has the potential to affect reproduction in daphnids and, therefore, the
      environment through the aquatic food chain.

PMID- 11990768
TI  - Intraspecific variation in trophic feeding levels and organochlorine
      concentrations in glaucous gulls (Larus hyperboreus) from Bjornoya, the Barents
      Sea.
AB  - Biomagnification contributes to high concentrations of persistent organochlorines
      (OC) in some Arctic vertebrates. Glaucous gulls (Larus hyperboreus) on Bjornoya
      in the western Barents Sea were studied to compare the intraspecific variation in
      OC concentration with variation in trophic feeding levels, estimated from ratios
      of nitrogen isotopes. Liver tissue samples from 40 adult glaucous gulls were
      analysed for hexachlorobenzene (HCB), oxychlordane, p,p'
      dichlorodiphenyltrichloroethane (DDT) and its metabolite p,p'-DDE, Mirex, and
      nine congeners of polychlorinated biphenyl (PCB). The ratios of the heavier to
      lighter isotope of carbon (13C/12C) and nitrogen (15N/14N), expressed as delta13C
      and delta15N, were measured in liver and muscle. Hepatic concentrations of the
      nine PCB congeners (Sigma 9 PCB) ranged from 16 microg/g lipid weight to 292
      microg/g lipid weight. The delta15N ranged from 14.0/1000 to 15.3/1000 in muscle.
      Seven of the 14 OC measured, sigma DDT, and sigma 9 PCB were positively
      correlated to delta15N from muscle tissue. No correlations were found between OC
      and delta13C. The present results indicate that OC concentrations are partly
      dependent on the foraging strategy of the gull. The r2 of the linear regressions
      suggests that up to 18% of the variation in the OC concentrations could be
      explained by variation in food preference.

PMID- 11990769
TI  - Decreased energetic reserves, morphological changes and accumulation of metals in
      carabid beetles (Poecilus cupreus L.) exposed to zinc- or cadmium-contaminated
      food.
AB  - The prime objective of the study was to find out whether contamination of food
      with metals affects body size, energetic reserves and developmental instability
      in ground beetles (Poecilus cupreus L.: Carabidae). The transfer of Cadmium (Cd)
      and Zinc (Zn) from medium (nominal concentrations in the medium: 0, 40, 160, 640
      or 800 mg kg(-1) for Cd and 0, 400, 1600 or 6400 mg kg(-1) for Zn) to housefly
      larvae to beetles was also studied. Feeding the beetles throughout their entire
      lifetime with Cd-contaminated housefly pupae resulted in a significant decrease
      in body caloric value and the size of the elytrae, tibiae and rear femora.
      Although body mass also decreased with increasing Cd concentration, this effect
      was non-significant due to large variance in all treatments. Similar trends were
      also found in beetles fed pupae contaminated with Zn, but the effect on body mass
      and caloric value was non-significant. Zn exerted significant effects only on the
      size of the elytrae, middle and rear tibiae, and front and rear femora. No effect
      on fluctuating asymmetry (FA) was found in Cd- or Zn-treated beetles. The results
      indicate that ground beetles exposed to metal-contaminated food have lower
      amounts of energy available, which may be reflected in lower energetic reserves
      and changed body growth. However, the metals do not cause developmental
      instability in the carabids studied, at least not in the first generation. The
      concentrations of Zn were efficiently regulated in carabids, resulting in only
      minor differences between the beetles exposed to different Zn treatments. In
      contrast, Cd accumulated both in the housefly and the beetles, and the
      concentrations increased significantly with increasing medium contamination
      level.

PMID- 11990770
TI  - Multiple stressor effects on benthic biodiversity of Chesapeake Bay: implications
      for ecological risk assessment.
AB  - In natural aquatic systems, there is frequently overlap in the spatial
      distribution of both natural and anthropogenic stressors, particularly at
      regional geographic scales. Yet the proportional risk associated with individual
      stressors, their cumulative effects and the manner in which they interact to
      affect aquatic ecology is frequently unknown, limiting the robustness of multiple
      stressor ecological risk assessments (ERA). The current study used historical
      environmental monitoring data (1984-1999) to identify a combination of natural
      and anthropogenic stressors that best accounted for observed patterns of benthic
      biodiversity in Chesapeake Bay. Geographic information systems (GIS) were used to
      geographically link spatially heterogeneous databases for benthic biodiversity,
      water quality and sediment toxicant concentrations. Single and multiple variable
      regression techniques were subsequently used to develop a statistical model to
      explain observed patterns of benthic biodiversity. Combinations of natural
      stressors alone accounted for as much as 34% of the variation in benthic
      biodiversity, and combinations of anthropogenic toxicants accounted for as much
      as 48% of the variation. The consideration of both natural and anthropogenic
      stressors resulted in a statistical model that accounted for approximately 73% of
      the observed variation in benthic biodiversity of Chesapeake Bay. These results
      suggest that benthic biodiversity in Chesapeake Bay is a function of complex
      interactions among water quality characteristics and anthropogenic toxicants.
      Therefore, new risk assessment methodologies are required to assess the risk of
      multiple stressors at regional scales.

PMID- 11990771
TI  - Clinical development of P glycoprotein modulators in oncology.
AB  - The last two decades have witnessed dramatic advances into the mechanisms of drug
      resistance in cancer. The identification of P glycoprotein (Pgp) as a specific
      mechanism led to the initial hope and expectation that it would be possible to
      modulate this and increase sensitivity to drug therapy. Clinical trials using
      first- and second-generation Pgp modulators did establish proof of principle that
      in some settings, clinical drug resistance could be overcome with the addition of
      a Pgp modulator-for example, clinical resistance to paclitaxel, a Pgp substrate,
      in women with ovarian cancer was shown to be overcome in approximately 20% with
      the addition of PSC 833, a highly effective Pgp modulator. However, evolutionary
      and adaptive redundancy in resistance mechanisms have tempered clinical results,
      even with very effective second- and third-generation modulators. The lessons
      from oncology establish sound methodology for the evaluation of Pgp modulators
      for safety, tolerability and efficacy in Phase I, II and III clinical trials.
      This review will focus on some of the early-phase clinical trials with earlier
      and newer Pgp modulators, either as single agents or in combination with
      chemotherapy.

PMID- 11990772
TI  - Gene expression profiling of epothilone A-resistant cells.
AB  - In the current study, we isolated sublines of the human breast adenocarcinoma
      cell line MDA 435 that exhibited increasing resistance to epothilone A, a
      microtubule-stabilizing cytotoxic agent. The resistant cells did not express P
      glycoprotein or multidrug resistance-associated protein (MRP) which are known
      mediators of multidrug resistance (MDR). Two groups of epothilone A-resistant
      cells were selected: cells which exhibited low resistance to both epothilone A
      and Taxol, and cells which exhibit low resistance to Taxol but high resistance to
      epothilone A. cDNA microarrays of epothilone A-resistant and Taxol-resistant
      cells were utilized to further characterize epothilone A resistance. Hierarchical
      clustering of genes according to their levels of expression indicated that the
      majority of genes which were highly expressed in epothilone A-resistant cells but
      not in taxol-resistant MDR cells encode known interferon-inducible proteins.
      Genes whose expression increased with increasing epothilone A resistance include
      microtubule-associated GTPases, cytoskeletal proteins, cell signalling proteins
      and a drug metabolising enzyme. The majority of the genes that were repressed in
      both epothilone A- and Taxol-resistant cells encode proteins regulating cellular
      growth signalling mechanisms.

PMID- 11990773
TI  - Imaging of P glycoprotein function in vivo with PET.
AB  - P glycoprotein (Pgp) is expressed on cell membranes of various organs in the
      body, such as the capillary endothelial cells of the brain. Furthermore, Pgp can
      also be expressed on the cell membrane of tumour cells. Because of Pgp-mediated
      efflux, tissue levels of several Pgp substrates are lower than in Pgp-negative
      tissues. Drug levels in Pgp-expressing organs may be increased by modulation of
      this Pgp-facilitated transport with several compounds, such as cyclosporin A. Up
      to now, the presence of drug efflux pumps in tissues could only be examined at
      the mRNA and protein level. However, this gives no insight into the important
      question of the functionality of these drug efflux pumps. Information about the
      transport function of Pgp and the effect of modulating this function may improve
      the therapeutic treatment of these patients. Positron emission tomography (PET)
      gives us a unique opportunity to study non-invasively (patho)physiological
      dynamic processes in vivo. We have therefore developed and validated a method for
      studying Pgp-mediated transport and its modulation in vivo with PET.

PMID- 11990774
TI  - Animal models of drug-resistant epilepsy.
AB  - It is not known why and how epilepsy becomes drug resistant in 20-30% of
      patients, while other patients with seemingly identical seizure types can achieve
      control of seizures with medication. An animal model of epilepsy allowing
      selection of pharmacoresistant and pharmacosensitive subgroups of animals would
      be a valuable tool to study mechanisms of pharmacoresistance and to develop more
      effective treatment strategies. Only a few models are available which mimic
      patterns of drug resistance in humans with epilepsy. One model seems to be
      particularly interesting: amygdala-kindled rats. In this model in Wistar rats,
      animals which do not respond to repeated or chronic administration of anti
      epileptic drugs (non-responders) can be separated from animals in whom anti
      epileptics are effective (responders). Hence, pharmacoresistant subgroups of
      kindled rats provide a unique tool to study why seizures become intractable,
      particularly because pathophysiological processes in these resistant rats can be
      directly compared with those of kindled rats that respond to treatment. By using
      this model, we have recently shown that both the individual genetic background
      and kindling-induced processes determine whether a rat becomes a responder or a
      non-responder to anticonvulsant treatment after kindling. We are currently
      studying the cellular mechanisms underlying the development of drug-resistant
      kindled seizures.

PMID- 11990775
TI  - Drug resistance in epilepsy: human epilepsy.
AB  - The basis of drug resistance in human epilepsy is not understood. Parallels with
      resistance in cancer suggest that drug resistance proteins may have a role. To
      examine this possibility, we have studied human brain tissue containing
      pathologies capable of causing refractory epilepsy. Using immunohistochemistry
      for P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1), we
      examined both pathological tissue and control tissue. We demonstrate expression
      of Pgp and MRP1 in glia from cases of malformation of cortical development
      studied both before and after the onset of epilepsy, as well as in cases of
      hippocampal sclerosis and dysembryoplastic neuroepithelial tumours. In one
      particular type of malformation, we also demonstrate that dysplastic neurons
      express MRP1. The pattern of immunolabelling suggests overexpression is
      concentrated particularly around vessels in most of the pathologies. The timing
      shows that expression may be constitutive in some pathologies. These findings
      suggest that drug resistance proteins may contribute to drug resistance in
      refractory epilepsy.

PMID- 11990776
TI  - Cellular mechanisms of pharmacoresistance in slices from epilepsy surgery.
AB  - Slices of human cortical tissue from epilepsy surgery were investigated with
      intracellular recordings to elucidate the mechanisms contributing to augmented
      synaptic excitation and to repetitive activity. The analysis of single synaptic
      potentials revealed, amongst other differences to rodent cortex, a disturbance of
      GABAA inhibition, namely depolarizing responses. A tentative ionic mechanism,
      impaired KCl outward-transport (KCC2), was evaluated in a rat model (0-Mg
      hyperexcitability). The observed down-regulation of KCC2 mRNA after 0-Mg-ACSF
      exposure of slices may contribute to the depolarizations by GABA. The factors
      enabling repetitive activity were addressed with a paired-pulse paradigm. In
      slices from epilepsy surgery, synaptic responses were virtually constant with
      interstimulus intervals between 100 and 1000 ms. Tiagabine markedly prolonged the
      effects of released GABA at GABAA receptors, but paired-pulse behaviour was only
      slightly affected. We demonstrate that bicuculline-induced paroxysmal activity of
      rat cortex is frequency-limited (to about <1 Hz) by presynaptic GABAB receptors.
      The lack of frequency limitation of synaptic events suggests an impaired GABAB
      receptor function in the human epileptogenic cortex. The data are discussed
      regarding the pivotal role of KCl transport in epileptic disorders of various
      origins and the role of GABAB receptors in the frequency limitation of paroxysmal
      activity.

PMID- 11990777
TI  - Drug resistance molecules: lessons from oncology.
AB  - Tumour cell insensitivity to anticancer drugs frequently appears as multidrug
      resistance (MDR), associated with overexpression of one or more of a set of at
      least 10 different molecules, causing reduced drug levels at the intracellular
      target sites. They include transmembrane transporter proteins such as P
      glycoprotein, MRP1-9 and BCRP. In addition, the lung-resistance protein, recently
      identified as the major vault protein, has been associated with MDR. We have
      generated monoclonal antibodies that specifically recognize most of these
      proteins, which we are using to try to identify their roles in clinical drug
      resistance, and also to explore their occurrence in normal human tissues and
      physiology. Both types of studies will also provide further insights into the
      molecular features of drugs associated with distinct MDR transporters.

PMID- 11990778
TI  - Functional polymorphisms of the human multidrug resistance (MDR1) gene:
      correlation with P glycoprotein expression and activity in vivo.
AB  - The human MDR1 gene encodes an integral membrane protein, P glycoprotein (Pgp),
      whose function is the energy dependent export of substances from the inside of
      cells, and from membranes, to the outside. Its physiological role is the
      protection of cells from toxic substances or metabolites. Many drugs that have
      been developed for the treatment of human diseases are substrates of Pgp. Because
      of that, the degree of expression and the functionality of the MDR1 gene product
      can directly affect the therapeutic effectiveness of such agents. This is of
      particular importance in cancer therapy where high expression and activity of
      MDR1 causes cancer cells to become refractory to the treatment with many agents,
      all of which are Pgp substrates. MDR1 is also expressed on different non
      malignant cells in various organs, e.g. in the intestine and at the blood brain
      barrier. Modulation of MDR1 expression in these normal cell types can also
      influence the activity and bioavailability of drugs. In the intestine, modulation
      of MDR1 may control the degree of drug uptake following drug ingestion. At the
      blood-brain barrier, Pgp may influence the uptake of substrates into the brain:
      high Pgp levels may limit the uptake of sufficient amounts of desired drugs into
      the brain, and reduced Pgp activity could lead to abnormally increased
      accumulation in the brain and undesired side effects of drugs.

PMID- 11990779
TI  - OC144-093, a novel P glycoprotein inhibitor for the enhancement of anti-epileptic
      therapy.
AB  - Inhibitors of P gLycoprotein (Pgp) may be useful for the enhancement of blood
      brain barrier penetration of anti-epileptic drugs (AEDs). Due to polypharmacy and
      the need for chronic treatment, Pgp inhibitors used in epilepsy should be highly
      specific and non-toxic. In particular, it may be essential to use compounds that
      produce minimal inhibition of enzymes involved in metabolism of AEDs and other
      drugs used by epilepsy patients. OC144-093 is a novel substituted diarylimidazole
      generated using the OntoBLOCK system, a solid-phase combinatorial chemistry
      technology, in combination with high-throughput cell-based screening. The
      compound is an extremely potent inhibitor of Pgp-mediated multidrug resistance
      (MDR) in cancer with an average FC50 of 32 nM, but does not inhibit multidrug
      resistance-associated protein (MRP1). OC144-093 is the least non-specifically
      toxic Pgp inhibitor described to date, with an average cytostatic IC50 of >60
      microM in 15 cell types. It is not metabolized by cytochrome P450s CYP3A4, 2C8 or
      2C9 enzymes involved in AED metabolism. OC144-093 does not produce a
      pharmacokinetic (PK) interaction with paclitaxel and has exhibited an excellent
      PK and safety profile in phase I clinical trials. Our results suggest that OC144
      093 may represent an ideal candidate for use in enhancement of AED blood-brain
      barrier penetration.

PMID- 11990780
TI  - Drug resistance in epilepsy: the role of the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is formed by the endothelial cells lining the brain
      microvessels. Complex tight junctions linking adjacent endothelial cells make
      brain capillaries around 100 times tighter than peripheral capillaries to small
      hydrophilic molecules. As a result, drugs required to act in the brain, including
      anti-epileptic drugs (AEDs), have generally been made lipophilic, and are thus
      able to cross the brain endothelium via the lipid membranes. However, such
      lipophilic drugs are potential substrates for efflux carriers of the BBB,
      particularly P glycoprotein (Pgp), predominantly located on the endothelial
      luminal membrane. It is estimated that up to 50% of drug candidates may be
      substrates for Pgp. The barrier phenotype of the brain endothelium is induced and
      maintained by chemical factors released by brain cells, particularly perivascular
      astrocytic end feet. In several neuropathological conditions, the BBB is
      disturbed, either as a result of pathology of the endothelium, or of the cells
      responsible for barrier induction and maintenance. During epileptic attacks,
      there may be transient BBB opening in the epileptogenic focus. There is evidence
      that under such pathological conditions, 'second line defence' mechanisms in
      perivascular glia may be up-regulated, including expression of Pgp and other drug
      efflux transporters. This complicates interpretation of drug resistance in
      epilepsy, and therapeutic strategies.

PMID- 11990781
TI  - The problem of the drug-resistant epilepsies.
AB  - For the majority of patients with epilepsy, the prognosis for seizure control is
      very good; however, refractory epilepsy develops in about 20-30% of patients and
      represents a significant challenge for both clinical management and for research.
      Physicians treating epilepsy are often asked to predict prognosis and make
      decisions about commencing and withdrawing treatment. Practice can be guided by
      epidemiological studies of prognosis. It seems that prognosis depends largely on
      the aetiology of the seizures and the clinical background of the patient rather
      than on the seizures themselves or the treatment prescribed. Aetiologies are,
      however, not the sole determinant of outcome and response to treatment and
      unknown factors must exit. It is likely that some of these unknown factors are
      genetically determined but this needs confirmation. The search for these unknown
      factors that may determine intractability in epilepsy is a very exciting
      prospect, which may prove to be multifactorial. In some patients, epilepsy may
      indeed become resistant to treatment whilst in others the propensity for
      intractability to the drugs currently available may be part and parcel of the
      condition. Further research is urgently needed to elucidate the full range of
      mechanisms that lead to drug resistant epilepsy.

PMID- 11990782
TI  - P glycoprotein and the mechanism of multidrug resistance.
AB  - The human P glycoprotein (Pgp; MDR1) is an ATP-driven transporter for hydrophobic
      drugs and causes multidrug resistance in cancer. Our knowledge related to the
      mechanistic details of the ATP hydrolytic cycle of MDR1 has recently
      significantly progressed due to studies on the formation of a catalytic
      intermediate (occluded nucleotide state). According to the most accepted current
      model, both catalytic sites in MDR1 are active and ATP is hydrolysed
      alternatively within the two sites. ATP hydrolysis at one site triggers
      conformational changes within the protein resulting in drug transport, while
      hydrolysis of a second ATP molecule (at the other site) is required for resetting
      the initial ('high-affinity binding') conformation. The two active sites act in a
      cooperative manner and experiments support a model where the two ATP binding
      cassette (ABC) domains form a coupled catalytic machinery. Although no high
      resolution structure is available as yet, some relevant structural information
      can be deduced from crystal structures obtained for several bacterial ABC units,
      and the recently solved bacterial ABC-ABC dimer crystal structures may provide
      the basis for a better understanding of the intramolecular cross-talk between the
      two catalytic sites. As intramolecular interactions between various domains of
      Pgp/MDR1 are essential in regulating both the ATPase and transport activity,
      compounds perturbing these interactions may interfere with the function of the
      transporter. Such compounds, as well as various substrate analogues may be useful
      in modulating multidrug resistance in cancer.

PMID- 11990783
TI  - Drug resistance caused by multidrug resistance-associated proteins.
AB  - Three types of drug efflux pumps, the multidrug resistance gene 1 (MDR1 or ABCB1)
      encoded P glycoprotein, the multidrug resistance-associated protein (MRP or
      ABCC1) and breast cancer resistance protein (BCRP or ABCG2) may play an important
      part in the intrinsic or acquired defence of cells against drugs. Recent studies
      have begun to show the broad tissue distribution and drug substrate specificity
      of the seven MRP family members (MRP1-7; or ABCC1-6 and ABCC10). MRPs are
      (multispecific) organic anion transporters, which can transport negatively
      charged anionic drugs and neutral drugs conjugated to glutathione, glucuronate or
      sulfate. MRP4 and MRP5 broaden the spectrum of drug resistance to nucleotide
      analogue drugs. Some MRPs can also transport neutral drugs if co-transported with
      glutathione. MRP1 and MRP5 are abundant in almost every organ and are prominently
      present in the brain. High levels of MRP1 are present in the epithelium of the
      choroid plexus. Using mutant mice lacking a functional Mrp1 gene, we have
      previously shown the contribution of MRP1 to the blood-CSF (cerebrospinal fluid)
      drug permeability barrier. Recent studies indicate that the very low levels of
      MRP1 or MDR1 present in fibroblasts affect their sensitivity to a wide range of
      clinically important cytotoxic drugs. Even low concentrations of drug
      transporters may therefore protect cells against drugs.

PMID- 11990785
TI  - An introduction to the genetics and biology of sex determination.

PMID- 11990784
TI  - Reversal of multidrug resistance: lessons from clinical oncology.
AB  - Modulation of P glycoprotein (Pgp) in clinical oncology has had limited success.
      Contributing factors have included the limitation in our understanding of the
      tumours in which Pgp overexpression is mechanistically important in clinical drug
      resistance; the failure to prove that concentrations of modulators achieved in
      patients were sufficient to inhibit Pgp; and the inability to conclusively prove
      that Pgp modulation was occurring in tumours in patients. New approaches are
      needed to determine the clinical settings in which Pgp overexpression plays a
      major role in resistance. (Clinical trials with third generation modulators are
      ongoing, including trials with the compounds LY335979, R101933 and XR9576. Using
      the Pgp substrate Tc-99m Sestamibi as an imaging agent, increased uptake has been
      seen in normal liver and kidney after administration of PSC 833, VX710 and
      XR9576. These studies confirm that the concentrations of modulator achieved in
      patients are able to increase uptake of a Pgp substrate. Furthermore, CD56+ cells
      obtained from patients treated with PSC 833 demonstrate enhanced rhodamine
      retention in an ex vivo assay after administration of the antagonist. Finally, a
      subset of patients treated with Pgp antagonists show enhanced Sestamibi retention
      in imaged tumours. These results suggest that Pgp modulators can increase drug
      accumulation in Pgp-expressing tumours and normal tissues in patients. Using
      third generation Pgp antagonists and properly designed clinical trials, it should
      be possible to determine the contribution of modulators to the reversal of
      clinical drug resistance.

PMID- 11990786
TI  - A comparative analysis of vertebrate sex determination.
AB  - Sex determination in vertebrates is controlled by a variety of mechanisms. We
      compared the expression of SF1, DAX1, DMRT1, SOX9 and AMH during gonadogenesis in
      the mouse, chicken and alligator embryo. In contrast to the expression profile of
      Sf1 in mouse embryos, chicken and alligator embryos show higher levels of Sf1
      expression in the developing ovaries compared to testes. This may reflect the
      higher level of sex hormone synthesis in the ovary compared to the testis in
      chickens and alligators. The DAX1 gene has a similar expression profile in all
      three vertebrate species but appears to have different gene structure. As in
      mouse, DMRT1 was expressed at very high levels in the chicken and alligator male
      gonad. The male-specific up-regulation of SOX9 expression appears to be a common
      feature in all three vertebrates. In the chicken and alligator AMH is expressed
      prior to SOX9, suggesting that in these species SOX9 cannot initiate AMH
      expression as it does in mammals. SOX9 acts at multiple points in the vertebrate
      testis pathway but it appears that only some of these functions have been
      conserved through evolution.

PMID- 11990787
TI  - Invertebrates may not be so different after all.
AB  - Sex determination is widespread, but uses highly varied molecular mechanisms. A
      possible case of conservation between phyla is that of doublesex (dsx) from
      Drosophila and mab-3 (male abnormal 3) from Caenorhabditis elegans, genes related
      in sequence and some elements of function. mab-3 controls multiple aspects of
      male development, including sense organ formation in the tail and yolk
      transcription in the intestine, both similar to functions of dsx. Indeed, the
      male isoform of DSX can replace MAB-3 in C. elegans. Do related genes control
      sexual development in vertebrates, despite great differences in the biology of
      sex determination? We have identified several dsx-related genes in mouse and
      human. One, Dmrt1, appears to play a conserved role in vertebrate male gonad
      development. In humans, DMRT1 maps to a short interval required for testis
      differentiation. In all vertebrates examined, including mammals, birds, fish, and
      reptiles, Dmrt1 is expressed early in the genital ridge, in most cases with
      higher expression in future male gonads. A null mutation in murine Dmrt1 causes
      severe defects in testis differentiation, resembling those associated with human
      deletions removing the gene. Mutant females are unaffected. Other DM domain genes
      are expressed in embryonic gonad and are currently under study.

PMID- 11990788
TI  - The hormonal control of sexual development.
AB  - The formation of the testis or ovary is a critical step in development. The
      pioneering studies of Professor Alfred Jost showed that the hormones produced by
      the embryonic rabbit testis are essential for development of the male phenotype.
      Sexually dimorphic hormones play a key role in the transition from an
      undifferentiated gonad into the mature testis and ovary. Marsupials, with their
      altricial young, provide an accessible model for the study of sexual
      differentiation because most of these events occur postnatally, while the young
      are attached to teats within their mothers' pouches. The relatively long time
      course for the marsupial sexual differentiation has provided an excellent
      opportunity to correlate morphological changes with the genes and hormones that
      control them. Using this model species we have demonstrated that not all sexual
      dimorphisms are controlled by hormones. Virilization of the prostate and phallus
      is androgen dependent but appears to rely on circulating 5alpha-androstane
      3alpha, 17beta-diol which is converted to dihydrotestosterone in these target
      tissues. Collectively these studies have led to the development of new paradigms
      to explain the hormonal mechanisms mediating sexual differentiation.

PMID- 11990789
TI  - Genetic studies of MIS signalling in sexual development.
AB  - The Mullerian ducts are composed of an epithelium and surrounding mesenchyme that
      have the potential to differentiate into female reproductive organs, including
      the oviducts, uterus and upper vagina. In eutherian mammals, Mullerian inhibiting
      substance/anti-Mullerian hormone (MIS/AMH) secreted by the fetal testis causes
      the regression of the Mullerian ducts to prevent the differentiation of female
      reproductive organs in males. MIS signalling in the Mullerian duct is mediated by
      the MIS type II receptor (MISRII) that is expressed in the mesenchyme surrounding
      the epithelium. MIS signalling alters the Mullerian duct mesenchyme, leading to
      the elimination of the ductal epithelium. Loss of MIS signalling, by mutation of
      MIS or MISRII, leads to the differentiation of female reproductive organs in
      males that can cause cryptorchidism and infertility. We have exploited the mouse
      MisrII locus to express heterologous genes in the cellular target of MIS
      signalling, the Mullerian duct mesenchyme. This approach can be used with
      conditional genetic strategies to identify factors that are required for the
      regression of the female genital duct system.

PMID- 11990790
TI  - Social regulation of the brain: sex, size and status.
AB  - Fish comprise the largest group of extant vertebrates with approximately 25,000
      known species. Some of these species are exceptional among vertebrates because
      they can change sex as adults. This observation raises ultimate questions about
      what selective forces led to the evolution of sex-changing ability and raises
      proximate questions about what mechanisms could account for this process. Sex
      change can be either from female to male (protogyny) or the reverse (protandry).
      In either case, the actual process of sex reversal requires reorganization of
      many critically important physiological systems from transformation of the gonads
      to modification of the neural and hormonal control systems. All of these changes
      require an individual animal to initiate the process based on information gleaned
      from the social situation. This is all the more remarkable because the
      information could be as simple as size discrimination or as complex as detecting
      subtle behavioural signals. Although it is self-evident that the brain controls
      behaviour, clearly behaviour can also 'control' the brain. How does behaviour
      cause changes in the brain? The work described here links molecular events with
      organismal behaviour by using an African cichlid fish model system in which
      social behaviours regulate reproduction. These animals have a complex social
      system based on the behaviour of two distinct classes of males, those with
      territories and those without. Changes in social status produced by behavioural
      interactions cause changes in neurons and endocrine responses. Surprisingly,
      growth rate is also regulated by social status and prior social history.
      Discovering how relevant social information is transduced into physiological
      processes requiring cellular and molecular action presents a major challenge.

PMID- 11990791
TI  - The battle of the sexes: opposing pathways in sex determination.
AB  - In mammals, a primordial gonad forms in XY and XX embryos that develops into a
      testis or an ovary depending on expression of Sry. Sry induces cell signalling
      pathways, including proliferation of Sertoli precursors and migration of
      peritubular myoid and vascular cells from the mesonephros. These events result in
      increased testis size and testis cord organization. Testis cord formation
      normally prohibits germ cells from entering meiosis. Ovarian fate is initiated in
      the absence of Sry, and has been proposed to be dependent upon the presence of
      meiotic germ cells in the gonad. We have shown that a developmental window exists
      during which testis development can be experimentally induced in XX gonads. This
      window closes just prior to the time that germ cells enter meiosis. Based on our
      work and much work that has preceded it, we suggest that the autonomous entry of
      germ cells into meiosis initiates the ovarian pathway and blocks testis
      development. Sry opposes this pathway by initiating testis cord formation prior
      to meiosis which sequesters germ cells inside cords and arrests them in mitosis.
      Current experiments in the lab address the hypothesis that cord formation and
      germ cell entry into meiosis are competing pathways in gonad development.

PMID- 11990792
TI  - The evolution of chromosomal sex determination.
AB  - There is a great diversity of sex determination mechanisms, with evidence for
      numerous evolutionary transitions between different systems. For example,
      environmental sex determination is widespread in lower vertebrates, and genetic
      sex determination has probably evolved from it several times. This requires the
      establishment of genes that override environmental cues. Close linkage between
      male and female determining loci is favoured by selection, and represents the
      first step towards the evolution of highly differentiated sex chromosomes. Once
      crossing over between primitive sex chromosomes has been suppressed, the
      primitive Y (W) chromosome is vulnerable to the operation of forces that lead to
      a reduction in its effective population size. This reduces the ability of natural
      selection to maintain the functionality of genes on the proto-Y, so that it
      gradually degenerates. Primitive sex chromosome systems, and systems of neo-X and
      neo-Y chromosomes formed by translocations involving autosomes and sex
      chromosomes, provide an opportunity to test evolutionary models of the
      degeneration of Y chromosomes and to determine the time-scales involved. Recent
      data confirm that newly-evolving Y or neo-Y chromosomes experience a sharp
      reduction in effective population size, and indicate that degeneration can occur
      over a few million generations.

PMID- 11990793
TI  - The molecular genetic jigsaw puzzle of vertebrate sex determination and its
      missing pieces.
AB  - Since the identification of SRY as the mammalian Y-chromosomal testis-determining
      gene a decade ago, more than a dozen additional genes essential for early gonadal
      development in mammals and other vertebrate classes have been identified. The
      location of these known pieces of the puzzle in the sex determination pathway,
      and how they interact, is briefly outlined. Two insights emerge: except for SRY,
      the same basic set of genes appears to operate during early gonadal development
      in all vertebrate classes, despite the difference in mechanisms; and vertebrate
      sex determination results from a complex network of regulatory interactions and
      not from a simple hierarchical cascade of gene actions. However, important pieces
      of the puzzle are still missing, such as the molecular nature of the sex switch
      in marsupials, monotremes and non-mammalian vertebrates; the target of SRY; the
      upstream regulators of SOX9; and the genes in the ovarian pathway. The enigma of
      SRY-positive XY gonadal dysgenesis females and SRY-negative XX males also
      indicates that the picture is still far from complete. Filling in these missing
      pieces is the challenge for the future.

PMID- 11990794
TI  - Early gonadal development: exploring Wt1 and Sox9 function.
AB  - Prior to sex determination the gonadal anlage is formed as a bipotential
      primordium with the capacity to differentiate into either testes or ovaries
      depending on the presence or absence of the Sry gene. Knockout experiments have
      implicated five genes in the formation or survival of the gonadal primordium:
      Wt1, Sf1, Lim1, Lhx9 and Emx2. We are particularly interested in the Wilms tumour
      suppressor, WT1, which is characterized by complex posttranscriptional
      modifications. Here we will focus on published in vitro evidence suggesting
      distinct functions for the various isoforms and present our own results from in
      vivo experiments. Our data suggest that WT1 is an important regulator of the
      transcription or stability of the sex-determining gene Sry. One of the first
      genes expressed after the initial male sex-determining signal is the Sox9 gene.
      Human SOX9 has been implicated in male-to-female sex reversal. To analyse Sox9
      function in mouse development we have performed transgenic experiments and
      ectopically expressed this gene in XX gonads. Our data indicate that Sox9 is
      sufficient to induce testis formation in mice. Here we will discuss our new data
      and present an updated model for Wt1 and Sox9 function in gonad formation and sex
      determination.

PMID- 11990795
TI  - Expression-based strategies for discovery of genes involved in testis and ovary
      development.
AB  - In recent years, strategies for gene identification based on differential gene
      expression have become increasingly popular, due in part to the development of
      microarray technology. These strategies are particularly well suited to the
      identification of genes involved in sex determination and gonadal development,
      which unlike the development of other organ systems, proceeds along two very
      different alternative courses, depending on the sex of the embryo. We have used a
      high-throughput, array-based expression screen to identify several genes
      expressed sex-specifically in developing mouse gonads. One of these, vanin 1,
      appears to play a role in mediating migration of mesonephric cells into the male
      genital ridge. Progress in characterizing other genes arising from the screen is
      discussed.

PMID- 11990796
TI  - Sex-determining genes in mice: building pathways.
AB  - Sry is active in the mouse for a very brief period in somatic cells of the
      genital ridge to initiate Sertoli cell differentiation. SRY protein must act
      within the context of other gene products required for gonadal development and
      must itself act on one or more target genes that will ensure the further
      differentiation and maintenance of Sertoli cells. Over the last few years several
      genes have been found that have important roles in gonadal development and sex
      determination. These include genes encoding transcription factors such as Lhx9,
      Wt1, Sf1, Dax1, Gata4, Dmrt1 and Sox9, and some involved in cell cell signalling,
      including Amh, Wnt4 and Dhh. While more await discovery, it is now possible to
      start putting some of the known genes into pathways or networks. Sox9 probably
      occupies a critical role in mammals for both the initiation and maintenance of
      Sertoli cell differentiation. Data will be presented that are consistent with SRY
      acting directly on Sox9 to ensure its up-regulation. SF1 is also central to
      gonadal differentiation. Our results imply that it contributes to transcriptional
      activation of several relevant genes, not just those required for male
      development, including Sox9 and Amh, but also those that can have an antagonistic
      effect on Sertoli cell differentiation, such as Dax1. Progress in establishing
      other regulatory interactions will also be discussed.

PMID- 11990797
TI  - Anomalies of human sexual development: clinical aspects and genetic analysis.
AB  - Disorders of human sex determination result in malformations of the external and
      internal genitalia. These malformations may vary from sexual ambiguity to
      complete sex reversal (XY female, XX male). Most of the knowledge of the
      molecular mechanisms involved in the mammalian sex determination pathway has been
      derived from the genetic analysis of intersex patients. Clinical management of
      these conditions critically depends on a precise understanding of their
      pathophysiology. Until recently, only transcription factors such as SRY, SOX9,
      DAX1, WT1 and SF1 were known to be responsible for abnormal gonadal development
      and sexual ambiguity. Gonadal dysgenesis may be isolated, as in the case of SRY
      mutations, or associated with abnormal development of other organs, such as bone
      or adrenals, consistent with the spatial expression profile of the disrupted
      genes (SOX9 or SF1). WNT4 is a new sex-determining signalling molecule. Deletions
      of Wnt4 were shown to be responsible for the masculinization of XX mouse pups
      while its duplication and overexpression in humans leads to XY sex reversal.
      Similarly, duplications of loci containing DAX1 or SOX9 have also been shown to
      cause sex reversal. These results support the emerging concept that mammalian sex
      determination is dosage sensitive at multiple steps of its pathway.

PMID- 11990798
TI  - The molecular action of testis-determining factors SRY and SOX9.
AB  - Despite 10 years of work since the discovery of SRY, little is known about its
      biochemical function. The HMG domain, a DNA-binding and DNA-bending motif, plays
      a central role, being the only region conserved between species and the site of
      almost all clinical mutations causing XY gonadal dysgenesis. By contrast, SOX9
      harbours a number of highly conserved regions, including two domains required for
      maximal transactivation. The beat shock protein HSP70 recognizes a specific
      region of SOX9 hitherto of unknown function which may facilitate the assembly of
      multi-protein complexes at promoter enhancer regions. The SRY and SOX9 HMG
      domains carry two nuclear localization signals (NLSs), one at each end which
      function independently and by distinct mechanisms. The N-terminal NLS is bound by
      calmodulin while the C-terminal NLS is bound by importin beta. Four XY gonadal
      dysgenesis patients with mutations in SRY NLS regions showed reduced nuclear
      import accompanied in some cases by reduced importin beta recognition. A
      campomelic dysplasia patient with SOX9 mutation outside the NLS regions also
      showed defective SOX9 nuclear import implying that nuclear import defects could
      be a common explanation for SRY and SOX9 HMG domain mutations.

PMID- 11990799
TI  - Concerted regulation of gonad differentiation by transcription factors and growth
      factors.
AB  - It is well known that signals from growth factors regulate gene transcription
      thus initiating certain steps of cellular and tissue differentiation during
      development. In gonad differentiation several transcription factors have been
      identified as the genes underlying human diseases displaying gonadal defects and
      as the genes necessary for gonad differentiation as demonstrated by gene
      disruption studies. In addition, one of the growth factors, WNT4, is known to be
      involved in gonadal differentiation. However, it remains unclear which gene is
      directly downstream of the WNT4 signal. We have recently demonstrated that Dax1
      (NR0B1) gene transcription is significantly up-regulated by the presence of SF1
      (NR5A1). Functional analysis showed that DAX1 acts as a repressor against SF1
      through direct interaction between the repeated sequences at the N-terminus of
      DAX1 and a ligand-binding domain of SF1. Considering that the expressions of
      these factors during gonad differentiation show a sexually dimorphic pattern, it
      is likely that the Dax1 gene transcription is up-regulated by WNT4 signal and
      thereafter DAX1 suppresses the genes downstream of SF1 such as Amh and
      steroidogenic genes in female gonads.

PMID- 11990800
TI  - Evolution of the testis-determining gene--the rise and fall of SRY.
AB  - The mammalian Y chromosome has been known for a long time to harbour a gene that
      triggers testis determination, and this testis-determining factor was identified
      as SRY in 1990. It has been supposed that SRY was the original mammalian sex
      determining gene that initiated the differentiation of the Y from the X early in
      mammalian evolution, and this belief has been reinforced by an analysis of
      divergence times. However, I will argue here that SRY evolved quite recently in
      therian mammals and was not the original mammalian sex-determining gene that
      defined the X and Y. It arose as a degraded version of the X-borne SOX gene that
      is better qualified to be a brain-determining gene. It has no central role in sex
      determination, and can be replaced as a trigger and lost, as have many other Y
      borne genes in recent evolutionary history. The mole vole has evidently
      accomplished this.

PMID- 11990801
TI  - Paraclinoid aneurysms.

PMID- 11990802
TI  - Radiometric analysis of paraclinoid carotid artery aneurysms.
AB  - OBJECT: Classification of paraclinoid carotid artery (CA) aneurysms based on
      their associated branching arteries has been confusing because superior
      hypophyseal arteries (SHAs) are too fine to appear opacified on cerebral
      angiograms. The authors performed a retrospective radiometric analysis of
      surgically treated paraclinoid aneurysms to elucidate their angiographic and
      anatomical characteristics. METHODS: A retrospective analysis was made of 85
      intradural paraclinoid aneurysms in which the presence or absence of branching
      arteries had been determined at the time of surgical clipping. The lesions were
      classified as supraclinoid, clinoid, and infraclinoid aneurysms based on their
      relation to the anterior clinoid process on lateral angiograms of the CA. The
      direction of the aneurysms were measured according to angles formed between the
      medial portion of the horizontal line crossing the aneurysm sac and the center of
      the aneurysm neck on anteroposterior angiograms. Branching arteries were
      associated with 68 aneurysms, of which 28 were ophthalmic artery (OphA) lesions
      (32.9%) and 40 were SHA ones (47.1%); associated branching arteries were absent
      in 17 aneurysms (20%). Twenty-five aneurysms (29.4%) were located at the
      supraclinoidal level, 46 (54.1%) at the clinoidal, and 14 (16.5%) at the
      infraclinoidal. The majority of aneurysms identified at the supraclinoidal level
      were OphA lesions (44%) or those unassociated with branching arteries (48%), with
      mean directions of 57 degrees or 67 degrees, respectively. At the clinoidal
      level, the mean directions of aneurysms were 76 degrees in six lesions
      unassociated with branching arteries (13%), 43 degrees in 16 OphA lesions (35%),
      and -11 degrees in 24 SHA ones (52%). All aneurysms at the infraclinoidal level
      arose at the origin of the SHAs, with a mean direction of -29 degrees, and most
      of these were embedded in the carotid cave. CONCLUSIONS: Aneurysms arising from
      the SHA can be distinguished from those not located at an arterial division by
      cerebral angiography, because SHA lesions are usually located at the medial or
      inferomedial wall of the internal carotid artery at the clinoidal or
      infraclinoidal level. Their distribution correlates well with the reported
      distribution of SHA origins. The carotid cave aneurysm is a kind of SHA lesion
      that originates at the most proximal intradural CA.

PMID- 11990803
TI  - Cranial remodeling to treat craniosynostosis by gradual distraction using a new
      device.
AB  - OBJECT: The authors describe their experience in remodeling the shape of the
      cranium in children with craniosynostosis by using gradual distraction. In half
      of the cases, a new distraction device developed by the authors was used.
      METHODS: Twenty children with craniosynostosis underwent frontoorbital
      advancement and cranial remodeling assisted by gradual distraction. There were
      five children with brachycephaly, two with oxycephaly, five with scaphocephaly,
      two with plagiocephaly, one with combined scaphocephaly and plagiocephaly, and
      five with trigonocephaly. Four cases were syndromic and 16 were nonsyndromic. The
      patients ranged in age from 3 to 50 months (mean 14.5 months) at the first
      surgery. Simulated surgery was first performed on a three-dimensional solid model
      made of polyurethane, which accurately represented cranial flexibility, to
      determine the most favorable osteotomy line. Distraction was initiated 1 week
      postoperatively. The speed and extent of advancement (maximum extension 45 mm)
      were predetermined on the basis of previously reported criteria and the results
      of simulated surgery. Postoperatively, the cranial configuration was favorable in
      all cases. Spontaneous remodeling of irregularities and/or gaps apparent after
      distraction was found to occur 2 to 5 months after removal of the distraction
      devices, especially in patients with trigonocephaly or scaphocephaly. No major
      perioperative complication was observed in any patient. There were minor
      complications in six of the first 10 cases, including exposure of the device,
      shaft slippage, and fluid discharge. A new device was developed and used on the
      last 10 patients treated; it successfully eliminated device exposure and shaft
      slippage. A 3-year follow-up review confirmed that there was no relapse of
      advanced bones. CONCLUSIONS: Highly satisfactory results were achieved in cases
      of both syndromic and nonsyndromic craniosynostosis when gradual distraction was
      performed.

PMID- 11990804
TI  - Subthalamic nucleus stimulation in patients with a prior pallidotomy.
AB  - OBJECT: A substantial number of patients with Parkinson disease (PD) who have
      undergone unilateral stereotactic pallidotomy ultimately develop symptom
      progression, becoming potential candidates for further surgical treatment.
      Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown
      to be effective in the treatment of a subset of patients with refractory PD.
      Microelectrode recording is performed to help localize the STN and guide final
      placement of the electrode. Potential alterations in physiological features of
      the STN after pallidotomy may complicate localization of this structure in this
      group of patients. METHODS: Bilateral STN DBS surgery guided by microelectrode
      recording was performed in six patients who had undergone previous unilateral
      pallidotomies. Physiologically obtained parameters of the STN, including
      trajectory length, mean firing rate, cell number, and cell density were
      calculated. These data were compared with those from the side without prior
      pallidotomy within each patient, as well as with those from our series of 49
      subthalamic nuclei explored in 26 patients who had not undergone prior
      pallidotomy but who underwent bilateral STN stimulator placement. In all
      patients, analysis of STN cellular activity on the side ipsilateral to the
      pallidotomy demonstrated a lower mean firing frequency than on the contralateral,
      intact side. The physiological features on the intact side were not significantly
      different from those found in our series of patients who had not undergone prior
      pallidotomy. CONCLUSIONS: Physicians who perform STN surgery in patients with
      prior pallidotomy should be aware of the electrophysiological differences between
      the STN that had undergone pallidotomy and the one that had not, to avoid
      prolonging recording time to search for the typical STN. The implications of
      these findings for the current models of information processing in the basal
      ganglia are discussed.

PMID- 11990805
TI  - Bilateral stimulation of the subthalamic nucleus in patients with Parkinson
      disease: a study of efficacy and safety.
AB  - OBJECT: Palliative neurosurgery has reemerged as a valid therapy for patients
      with advanced Parkinson disease (PD) that is complicated by severe motor
      fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS)
      of the subthalamic nucleus (STN), existing reports on this treatment are limited.
      The present study was designed to investigate the safety and efficacy of
      bilateral stimulation of the STN for the treatment of PD. METHODS: In 12 patients
      with severe PD, electrodes were stereotactically implanted into the STN with the
      assistance of electrophysiological conformation of the target location. All
      patients were evaluated preoperatively during both medication-off and -on
      conditions, as well as postoperatively at 3, 6, and 12 months during medication
      on and -off states and stimulation-on and -off conditions. Tests included
      assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and
      timed motor tests. The stimulation effect was significant in patients who were in
      the medication-off state, resulting in a 47% improvement in the UPDRS Part III
      (Motor Examination) score at 12 months, compared with preoperative status. The
      benefit was stable for the duration of the follow-up period. Stimulation produced
      no additional benefit during the medication-on state, however, when compared with
      patient preoperative status. Significant improvements were made in reducing
      dyskinesias, fluctuations, and duration of off periods. CONCLUSIONS: This study
      demonstrates that DBS of the STN is an effective treatment for patients with
      advanced, medication-refractory PD. Deep brain stimulation of the STN produced
      robust improvements in motor performance in these severely disabled patients
      while they were in the medication-off state. Serious adverse events were common
      in this cohort; however, only two patients suffered permanent sequelae.

PMID- 11990806
TI  - Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting
      of the globus pallidus internus in the performance of deep brain stimulation for
      treatment of dystonia.
AB  - OBJECT: To assess the validity of relying on atlases during stereotactic
      neurosurgery, the authors compared target coordinates in the globus pallidus
      internus (GPi) obtained using magnetic resonance (MR) imaging with those
      determined using an atlas. The targets were used in deep brain stimulation (DBS)
      for the treatment of generalized dystonia. METHODS: Thirty-five patients, who
      were treated using bilateral DBS of the GPi, were included in this study. The
      target was selected on three-dimensional MR images by direct visual recognition
      of the GPi. The coordinates were automatically recorded using dedicated software.
      They were translated into the anterior commissure-posterior commissure (AC-PC)
      coordinate system by using a matrix transformation process. The same GPi target
      was defined, based on the locations of brain structures shown in the atlases of
      Schaltenbrand and Talairach. Magnetic resonance imaging-based GPi target
      coordinates were statistically compared with the corresponding atlas-based
      coordinates by applying the Student t-test. A significant difference (p < 0.001)
      was demonstrated in x, y, and z directions between MR imaging-based and
      Schaltenbrand atlas-derived target coordinates. The comparison with normalized
      Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in
      the y and z directions, although not in the x direction (p = 0.12). No
      significant correlation existed between MR imaging-based target coordinates and
      patient age (p > 0.1). No significant correlation was observed between MR imaging
      based target coordinates and patient sex in the y and z directions (p > 0.9),
      although it was significant in the x direction (p < 0.05). A significant
      variation in coordinates and the length of the AC-PC line was revealed only in
      the y direction (p < 0.005). CONCLUSIONS: A significant difference was found
      between target coordinates obtained by direct visual targeting on MR images
      (validated by postoperative clinical results) and those obtained by indirect
      targeting based on atlases.

PMID- 11990807
TI  - Reversible dementia in patients with chronic subdural hematomas.
AB  - OBJECT: Neuropsychiatric changes following surgery for chronic subdural hematomas
      (CSDHs) were analyzed in 26 patients (21 men and five women) by using the Mini
      Mental State Examination (MMSE) and the Hasegawa Dementia Scale-Revised (HDS-R)
      to determine factors that potentially contribute to neuropsychiatric recovery.
      METHODS: Burr hole irrigation was performed in every patient to treat the CSDH.
      The patients' profiles, including age and sex, neuroimaging findings (such as
      hematoma volume and thickness, as well as midline shift), and preoperative and
      postoperative scores on the MMSE, HDS-R, and activities of daily living (ADL)
      scale were recorded. According to preoperative MMSE scores, eight patients
      (30.8%) were classified as mentally healthy and 18 (69.2%) as suffering from
      dementia before surgery. Nine of the 18 patients with dementia recovered to a
      normal psychological state following surgery. Surgery improved not only the
      patients' independence in ADL (p = 0.0026), but also their neuropsychiatric
      functions such as orientation and calculation, as estimated by scores on the MMSE
      (p = 0.0002) and the HDS-R (p = 0.0008). Factors affecting neuropsychiatric
      status on admission were midline shift (p = 0.0398) and ADL score (p = 0.0124);
      factors that could be used to predict neuropsychiatric recovery after surgery
      were patient age (p = 0.0027) and ADL score (p = 0.0193). The results of a
      logistic regression analysis demonstrated that significant predictors of
      neuropsychiatric recovery after surgery include the following: patient age (p =
      0.0049, odds ratio [OR] = 0.842) and preoperative ADL (p = 0.0056, OR = 0.471),
      MMSE (p < 0.0001, OR = 1.895), and HDS-R (p = 0.0073, OR = 1.303) scores. Results
      of subgroup analyses demonstrated that patients younger than 74 years of age and
      those who had preoperative scores lower than 5 on the converted ADL scale, higher
      than 10 on the MMSE, or higher than 9 on the HDS-R on admission were found to
      have a significantly better recovery of neuropsychiatric functions after surgery.
      CONCLUSIONS: Dementia is reversible in many patients with CSDH, and surgery can
      improve not only independence in ADL, but also neuropsychiatric functions.
      Patients who are younger and/or those who have lower preoperative ADL scores
      and/or higher preoperative MMSE or HDS-R scores will achieve a good recovery with
      regard to neuropsychiatric functions after surgery. Estimations of
      neuropsychiatric function based on MMSE and HDS-R scores were found to be useful
      in predicting functional outcomes in patients with CSDH.

PMID- 11990808
TI  - Detection of hyperacute subarachnoid hemorrhage of the brain by using magnetic
      resonance imaging.
AB  - OBJECT: The purpose of this study was to determine the diagnostic accuracy of
      high-field (1.5-tesla) magnetic resonance (MR) imaging in the assessment of
      hyperacute (< 12 hours after onset of symptoms) subarachnoid hemorrhage (SAH).
      METHODS: This investigation included 13 patients who were examined 2 to 12 hours
      posthemorrhage by using an MR imaging protocol consisting of T2-weighted and
      proton-density (PD)-weighted images, T1-weighted images, fast echoplanar
      diffusion-weighted (EP-DW) images, and fluid-attenuated inversion-recovery
      (FLAIR) images. Subarachnoid hemorrhage had been diagnosed using computerized
      tomography (CT) scanning in all cases. In all 13 cases, SAH was reliably detected
      on both PD-weighted and FLAIR images. In contrast with FLAIR studies, the PD
      weighted images were free of cerebrospinal fluid flow artifacts. The SAH was
      detected on T1-weighted images in only two cases and could not be detected on any
      T2-weighted or EP-DW images. CONCLUSIONS: Even hyperacute SAH can be diagnosed
      reliably from high-field MR images obtained using PD-weighted or FLAIR sequences.
      Use of these sequences in an emergency MR protocol may preclude the need for
      additional CT studies to rule out SAH.

PMID- 11990809
TI  - Waterjet dissection in neurosurgical procedures: clinical results in 35 patients.
AB  - OBJECT: Waterjet dissection represents a new minimally traumatic surgical method
      for dissection that can be used in various parenchymal organs, in which it allows
      highly precise parenchymal dissection while preserving blood vessels, resulting
      in reduced intraoperative blood loss. This study was performed to investigate the
      clinical application of this new technique in neurosurgical procedures, such as
      brain tumor resection and epilepsy surgery. METHODS: Thirty-four patients with
      gliomas (Grades II-IV), cerebral metastases, temporal lobe epilepsy, or
      cerebellar hemangioblastomas, and one patient with internal carotid artery (ICA)
      stenosis were treated surgically with the aid of the waterjet. Resection was
      performed using waterjet dissection in combination with conventional
      neurosurgical procedures. Intraoperatively, the waterjet was easy to handle, and
      no complications due to the device were observed. Dissection of tissue was
      possible for all pathological conditions, and pressures between 3 and 45 bars
      were used. In gliomas, metastases, epilepsy surgery, and hemangioblastoma, the
      tissue was dissected at pressures between 3 and 17 bars, which preserved blood
      vessels. Dissection of meningiomas and the ICA stenosis required higher pressures
      (between 20 and 45 bars); with these pressures, blood vessels were also
      dissected. CONCLUSIONS: These results indicate that the waterjet dissection
      procedure can be used intraoperatively without complications. This device appears
      to be particularly suitable for the dissection of highly vascularized gliomas or
      normal brain tissue, in which tissue dissection with sparing of blood vessels can
      be achieved. To prove that this is a useful addition to the neurosurgical
      armamentarium, reduction of blood loss or postoperative brain edema compared with
      conventional methods should be demonstrated in future studies.

PMID- 11990810
TI  - Magnetic resonance angiographic evidence of sex-linked variations in the circle
      of willis and the occurrence of cerebral aneurysms.
AB  - OBJECT: In this study the authors investigated the relationship between
      variations in the circle of Willis observed on magnetic resonance (MR) angiograms
      and locations of cerebral aneurysms, and evaluated the risk of aneurysm
      formation. METHODS: One hundred thirty-one patients with cerebral aneurysms were
      retrospectively selected from a series of 4518 patients who underwent MR
      angiography at one neurosurgical institute. Variations in the anatomy of the
      circle of Willis were simply classified into Type A, in which there was no
      visualization of a unilateral A1 segment, and Type P, in which there was a fetal
      type of posterior cerebral artery that was continuously delineated from the
      internal carotid artery (ICA) through the posterior communicating artery. All
      other variations in the circle of Willis were defined as Type O (ordinary type of
      variations). An additional 440 patients who did not harbor cerebral aneurysms
      were randomly selected for a comparison. Anterior communicating artery aneurysms
      were significantly related to the Type A anatomy and ICA aneurysms to Type P
      anatomy. Male patients who did not harbor aneurysms tended to have Type A
      anatomy, whereas women had a significantly greater incidence of Type P.
      CONCLUSIONS: This sex-linked difference in anatomical variations may be
      correlated to the well-known sex-linked difference in aneurysm distribution.

PMID- 11990811
TI  - Surgical outcomes in 31 patients with craniopharyngiomas extending outside the
      suprasellar cistern: an evaluation of the frontobasal interhemispheric approach.
AB  - OBJECT: Craniopharyngiomas frequently grow from remnants of the Rathke pouch,
      which is located on the cisternal surface of the hypothalamic region. These
      lesions can also extend elsewhere in the infundibulohypophyseal axis. The aim of
      this study was to establish the usefulness of the frontobasal approach made
      through a relatively small craniotomy window for the removal of tumors protruding
      from the sellar-suprasellar region into the third and basal cistern. METHODS:
      Thirty-one patients who were surgically treated for craniopharyngiomas extending
      outside the sellar-suprasellar region were evaluated. The diagnoses were
      established in all cases by using magnetic resonance and computerized tomography
      imaging. The initial symptoms and signs were increased intracranial pressure in
      eight, vision impairment or visual field defect in 16, hypopituitarism in 17, and
      psychological disturbances in three cases. All patients underwent surgery via the
      frontobasal interhemispheric approach, and the average follow-up period was 30
      months. Total removal of the lesion was achieved in 22 cases, six patients
      underwent subtotal resection, and three underwent partial removal due to tumor
      recurrence after previous surgeries performed with or without adjunctive
      radiotherapy. Major complications, including impairment of the cranial nerves,
      were not observed in the immediate postoperative period. One patient exhibited
      transient memory disturbance due to infarction of the perforating vessels; after
      3 months this symptom was ameliorated. None of the patients died during long-term
      follow up; however, four of the 22 who underwent total removal and six of the
      nine patients who underwent subtotal or partial removal suffered recurrence. Of
      the 10 patients with recurrence, six experienced a small recurrence of the lesion
      (average 3 months postsurgery); after gamma knife surgery (GKS), the size of two
      of the lesions was unchanged and in four reoperation was performed due to tumor
      enlargement during the follow-up period. Ultimately, a total of eight patients
      (four with recurrence and four who had been treated with GKS) underwent
      reoperation, with gross-total removal via the same approach or combined with the
      orbitozygomatic approach in patients with very short optic nerves. In no patient
      was deterioration of visual acuity and visual field observed after surgery.
      Although all patients except four children and one adult were receiving some form
      of hormone replacement therapy, their endocrine status was stably controllable.
      CONCLUSIONS: In the authors' experience, the frontobasal interhemispheric
      approach, even made through a small craniotomy window, is a valid choice for the
      removal of craniopharyngiomas extending outside the sellar-suprasellar region.
      Via this approach, tumors can be removed without significant sequelae related to
      the surgical method, due to ease of preservation of the pituitary stalk,
      hypothalamic structures, and perforating vessels. This approach offers a safe and
      minimally invasive means of treating craniopharyngiomas.

PMID- 11990812
TI  - Integration of sulcal and functional information for multimodal neuronavigation.
AB  - OBJECT: The authors present the use of cortical sulci, segmented from magnetic
      resonance (MR) imaging, and functional data from functional (f)MR imaging and
      magnetoencephalography (MEG) in the image-guided surgical management of lesions
      adjacent to the sensorimotor cortex. METHODS: In an initial set of 11 patients,
      sulci near lesions were automatically segmented from MR imaging data sets, then
      MEG and fMR imaging examinations were performed. Relevant functional information
      was preoperatively interpreted and selected from MEG and fMR imaging and
      subsequently transferred to the navigation system for selected sulci. A
      neuronavigation system consisting of a surgical microscope with enhanced reality
      overlay display was used. Data were displayed as contours on the cut-plane images
      of a stereotactic workstation and as contours on the overlay screen of the head
      up display within the optical path of the right eyepiece of the surgical
      microscope. CONCLUSIONS: This method, in which both sulcal and functional mapping
      are used for surgery planning and neuronavigation, provides helpful information.
      It is a promising procedure for the treatment of patients who harbor lesions in
      areas around the eloquent cortex.

PMID- 11990813
TI  - Detection and significance of focal, interictal, slow-wave activity visualized by
      magnetoencephalography for localization of a primary epileptogenic region.
AB  - OBJECT: Magnetoencephalography (MEG) is a novel noninvasive diagnostic tool used
      to determine preoperatively the location of the epileptogenic zone in patients
      with epilepsy. The presence of focal slowing of activity recorded by
      electroencephalography (EEG) is an additional indicator of an underlying
      pathological condition in cases of intractable mesial temporal lobe epilepsy
      (MTLE). In the present study the authors examined the significance of focal, slow
      wave and interictal spike activity detected using MEG in 29 patients who suffered
      from MTLE that was not associated with structural brain lesions. METHODS: All
      patients underwent resective surgery after MEG and EEG monitoring. Equivalent
      single-dipole modeling was applied to focal low-frequency magnetic activity
      (LFMA) and interictal paroxysmal activity. Lateralized LFMA was defined as trains
      of rhythmic activity over the temporal area, with frequencies lower than 7 Hz,
      which were easily distinguished from background activity. Lateralized LFMA was
      found in 17 patients (58.6%); it always occurred on the side ipsilateral to the
      side of resection and displayed a maximum amplitude over the temporal area.
      Dipolar sources of magnetic flux computed during slow-wave trains were found in
      the majority of cases in the posterior superior temporal region and,
      occasionally, in mesial temporal structures that were subsequently resected. With
      respect to lateralization there was never disagreement between LFMA and MEG
      interictal spike sources. Thus, in patients with MTLE that is not associated with
      a mass lesion LFMA is topographically related to the epileptogenic area and,
      therefore, has value for reliable determination of the side and, possibly, the
      location of this area. CONCLUSIONS: Although focal slowing of EEG background
      activity is generally considered to be a nonspecific sign of functional
      disturbance, interictal LFMA in patients with MTLE should be conceptualized as a
      distinct electrographic phenomenon that is directly related to the epileptogenic
      abnormality. Analyzing the interictal MEG distribution of LFMA and sharp activity
      improves the diagnostic utility of MEG in patients with suspected TLE who are
      undergoing surgical evaluation.

PMID- 11990814
TI  - Clinical application of a new bioabsorbable artificial dura mater.
AB  - OBJECT: In their pursuit of a better substitute for dura mater in neurosurgical
      procedures, the authors review their experience with GM972. METHODS: A newly
      developed synthetic dural substitute composed of bioabsorbable polymers (GM972)
      was placed in 53 patients during neurosurgical procedures. The handling
      properties of the material, surgical wound features. and findings of
      hematological, computerized tomography, and/or magnetic resonance imaging
      examinations were evaluated. The average follow-up period was 35.5 months. The
      handling properties and biocompatibility of this new dural substitute were highly
      satisfactory, and no significant complication was observed. In patients who
      underwent a second surgery performed more than 18 months after the initial
      operation, this new dural substitute was found to have been replaced by
      autologous collagenous tissue. Because of its bioabsorbability, chronic foreign
      body reactions to this synthetic dural substitute were negligible. CONCLUSIONS:
      In this report the authors support the effectiveness and safety of this
      bioabsorbable artificial dural substitute that provides a reduced risk of
      transmission of latent infection.

PMID- 11990815
TI  - Reversible ischemia around intracerebral hemorrhage: a single-photon emission
      computerized tomography study.
AB  - OBJECT: A zone of perilesional ischemia has been demonstrated around
      intracerebral hemorrhage (ICH) in numerous experimental models and in human
      studies. There is potential for perfusion recovery in the zone of perilesional
      oligemia around ICH. The authors sought to demonstrate, quantify, and study the
      chronological evolution of perilesional ischemic change in ICH in humans by
      measuring cerebral blood flow. METHODS: Eleven patients with spontaneous
      supratentorial ICH underwent two technetium-99m hexamethylpropyleneamine oxime
      single-photon emission computerized tomography (SPECT) scanning, one in the acute
      stage (within days of ictus) and the other in the late stage (6-9 months
      postictus). All patients in this study were treated nonsurgically. Methods of
      SPECT data analysis based on count differences in regions of interest can be
      difficult to apply to images with large space-occupying lesions such as ICH,
      because of the distortion of intracranial anatomy, midline shift, and alterations
      in the three-dimensional (3D) characteristics of the lesion over time (that is,
      absorption of the hematoma on the later studies). The authors used the following
      method: the late and early images were registered and aligned to a common 3D
      orientation and were normalized to maximal counts. The late images were then
      compared voxel by voxel with the early ones. The region-growing algorithm was
      used to discern the difference between the two images, outlining voxels in the
      perihematoma region, with a signal improvement of at least 15% on the late image.
      Discrete brain regions around the hematoma with at least a 15% improvement in
      radiotracer uptake (and hence perfusion) in the late images were observed in all
      cases. The mean volume of brain with a greater than 15% improvement in perfusion
      between the two studies was 34.8 cm3 (range 7.2-71.3 cm3). These volumes
      represent regions of the brain that were poorly perfused in the initial studies.
      This may represent a zone of reversible perilesional oligemia (penumbra) in ICH
      in humans. CONCLUSIONS: This is the first study in which it is documented that
      some of the perilesional hypoperfused tissue around human ICH regains its
      perfusion in the long term, leading the authors to suggest that there may be a
      penumbra in human ICH. Medical or surgical therapeutic interventions could
      increase the volume of perilesional brain that recovers after the initial insult.
      The results of this study therefore support the concept that intervention in ICH
      has the potential to reduce the ultimate neurological deficit and improve
      outcome.

PMID- 11990816
TI  - Normal changes in orbital volume during childhood.
AB  - OBJECT: The aim of this study was to construct a model of changes in orbital
      volume that occur throughout childhood from the age of 1 month to 15 years, which
      could be used for comparative studies of disease states affecting orbital growth.
      METHODS: Using the procedure of segmentation on magnetic resonance images
      obtained in 67 healthy children, orbital volume was measured and plotted against
      age. During the first few months of life left orbital volume is on average 15 cm3
      in male and 13 cm3 in female infants; these volumes increase to 26 cm3 and 24
      cm3, respectively, by the time the child reaches 15 years of age. During the
      first few months of life right orbital volume is on average 16 cm3 in male and 13
      cm3 in female infants; these volumes increase to 27 cm3 and 25 cm3, respectively,
      by the time the child is 15 years old. This represents an overall increase in
      orbital volume by a factor of 1.7 in boys and 1.8 in girls. By the time the child
      has reached 5 years of age, the orbital volume for both right and left sides has
      reached on average 77% of the volume seen at 15 years in both sexes. The
      differences between the two sides are not statistically significant for either
      sex. The change in orbital volume that is associated with age in general displays
      a linear pattern. Throughout childhood, orbital volumes are larger in boys than
      in girls, but share a similar growth pattern. The difference between the two
      sexes tends toward statistical significance during the first 5 years of life
      (left orbit p = 0.1, right orbit p = 0.04). CONCLUSIONS: During early childhood,
      orbital volume increases in a linear fashion, achieving a significant proportion
      of its final growth by the time the child is 5 years old.

PMID- 11990817
TI  - Changes in orbital volume during childhood in cases of craniosynostosis.
AB  - OBJECT: Controversy remains concerning the timing of frontoorbital advancement
      (FOA) surgery performed for craniosynostosis. Reduced orbital volume and degree
      of exorbitism are often cited as reasons for early surgical intervention. To
      date, however, little attention has been given to orbital volume and its changes
      during the first few years of life as an indicator of orbital growth in children
      with craniosynostosis. Knowledge of orbital volume and growth patterns in
      individuals with craniosynostosis and those with normal cranial structures will
      enable surgeons to refine both the type and timing of surgical intervention
      required, thus obtaining the optimum outcome for their patients. METHODS: Using
      the procedure of segmentation, orbital volumes in 50 children with various forms
      of craniosynostosis were measured on preoperative computerized tomography scans.
      Changes in average volume that occur with increasing age were calculated and
      compared with a model of normal orbital volume growth. At presentation the
      children with craniosynostosis ranged in age from 1 to 29 months, with 82% of
      them within the 1st year of life. Several interesting observations emerged from
      this study. Excluding patients with unilateral coronal synostosis, there was no
      difference between orbital volumes measured on the right and left sides, allowing
      mean orbital volume measurements to be used for comparative purposes. Although
      children with craniosynostosis begin life with significantly smaller orbital
      volumes, overall normal mean volumes for both sexes are attained by 13 months of
      age, with volumes approaching normal by 6 months of age in male infants and by 8
      months of age in female infants. Changes in orbital volume associated with age
      generally appear to be similar in most forms of craniosynostosis. There appears
      to be no significant difference in changes in orbital volume between children
      with syndromic or nonsyndromic forms of bicoronal synostosis. Orbital volume is
      significantly reduced on the ipsilateral affected side in cases of unicoronal
      synostosis in comparison with the contalateral side, but it is not significantly
      lower than that of normal. Finally, FOA surgery appears to restore normal growth
      of orbital volume. CONCLUSIONS: The results of this study indicate that the
      underlying mechanism leading to craniosynostosis and restriction of orbital
      volume "burns out" and begins to lose its major effects within the first few
      months of life. It would appear that FOA surgery should be delayed until the end
      of the second half of the 1st year of life, thus maximizing the effects of
      accelerated normal orbital growth and reducing the risks of relapse.

PMID- 11990818
TI  - Magnetic resonance neurography of peripheral nerve following experimental crush
      injury, and correlation with functional deficit.
AB  - OBJECT: In a number of clinical studies magnetic resonance (MR) neurography has
      been used to examine patients with peripheral nerve damage, but little is
      understood about the sequence of imaging changes following nerve injuries, and
      how they correlate with functional deficit. The goal of this study was to further
      understanding of these changes and their implications. METHODS: Using the rat
      sciatic nerve crush model, the sciatic nerve was imaged at intervals over 70 days
      in 12 rats. Sham-operated contralateral nerves served as controls. A 4.7-tesla MR
      imager with a custom-made surface coil was used. The T2 maps were calculated from
      images obtained at four echo times and from regions of interest designated on the
      nerve at three sites. Walking-track analysis was performed at the same intervals
      as imaging. Magnetic resonance neurography revealed a mean T2 of normal sciatic
      nerve of 36 msec (standard deviation [SD] 1.2 msec). Crushed nerves demonstrated
      a sequence of changes in signal intensity that were maximal at 14 days, with a
      mean T2 of 64 msec (SD 5.2 msec), then falling to a T2 of 53 msec (SD 3.7 msec).
      Sham-operated nerves had a short and nonsustained rise in signal at 7 days.
      Walking-track analysis revealed maximum deficit immediately postinjury, with an
      improvement in function approaching that of control nerves at 30 days.
      CONCLUSIONS: In this study the authors demonstrate that quantitative assessment
      of nerve signals with MR neurography allows the sequence of events following
      nerve crush injury to be followed in vivo, and that a return toward a normal
      signal correlates with functional improvement. Assessment of peripheral nerve
      injury in patients by using MR neurography has the potential to confirm acute
      nerve injury as well as to monitor the recovery process.

PMID- 11990819
TI  - Polyester meshes and adhesive materials in the brain: comparative research in
      rats to optimize surgical strategy.
AB  - OBJECT: The goal of this study was to determine the biocompatibility of polyester
      mesh electrode carriers for auditory brainstem implants with and without
      adhesives in a rat model. METHODS: Physical properties of the meshes were
      evaluated within the fourth ventricle region, both without (Group A) and with
      adhesives (muscle, Group B; oxidized regenerated cellulose [ORC], Group C; and
      fibrin glue, Group D). The stability of the mesh position, the healing process,
      and host defense reaction after 2 to 60 days were examined in series of tissue
      sections in which meshes were preserved in situ. The cellular reaction was
      further evaluated using electron microscopy. Although otherwise pliable,
      polyester meshes were too rigid when used with adhesives, especially fibrin glue
      or muscle. Also, the sharp edges of the meshes presented a risk of brainstem and
      cerebellar lesions. Regardless of the material, meshes induced persistent
      inflammatory tissue reactions characterized by numerous macrophages and foreign
      body giant cells. After 14 days, the cellular response had resulted in sufficient
      fibroblast and collagen fiber encapsulation of the meshes and remained
      essentially unchanged thereafter. No influence of adhesives on the healing
      process was observed, and, unexpectedly, these substances did not reduce the risk
      of dislocation prior to adequate cellular encasement. In some rats in Groups A
      and C, purulent inflammation, in part with Gram-positive bacteria, occurred after
      2 to 14 days. The ORC exhibited persistent swelling, introducing the risk of
      occlusive hydrocephalus and/or brainstem compression. CONCLUSIONS: Polyester
      meshes and various adhesives exhibited acceptable biocompatibility in terms of
      local tissue reaction. Adhesives reduced pliability of the meshes, however, and
      were ineffective in reducing the risk of dislocation. Handling characteristics
      could be improved by better mesh designs, and risk of infection could be reduced
      by both improved designs and surface treatment of the meshes with antibacterial
      agents.

PMID- 11990820
TI  - Compartments in arteriovenous malformation nidi demonstrated with rotational
      three-dimensional digital subtraction angiography by using selective
      microcatheterization. Report of three cases.
AB  - Although in several histological studies of arteriovenous malformation (AVM) nidi
      the presence of compartments has been documented, no clinical study has been
      published. The present study was conducted to determine the presence of nidus
      compartments in clinical cases by using a new radiographic method. Two patients
      with unruptured and one with a ruptured AVM (all Spetzler-Martin Grade III) were
      studied. A microcatheter was superselectively introduced into each of two or
      three feeding arteries of the AVMs under three-dimensional (3D) angiographic
      guidance to obtain 3D images of the nidus by using rotational digital subtraction
      angiography. On 3D images the different feeding arteries were found to be
      independent from one another, which allowed the authors to confirm the presence
      of compartments. On the other hand, separate feeding arteries often had a common
      draining vessel. Compartments in AVM nidi were demonstrated by a novel rotational
      3D angiographic procedure by using superselective microcatheterization, which
      should be useful for designing treatment strategies for large and complex AVMs.

PMID- 11990821
TI  - Clinical and molecular analysis of disseminated hemangioblastomatosis of the
      central nervous system in patients without von Hippel-Lindau disease. Report of
      four cases.
AB  - Hemangioblastomas of the central nervous system (CNS) may occur sporadically or
      in association with von Hippel-Lindau (VHL) syndrome. The authors present four
      patients with no family history or clinical evidence of VHL syndrome in whom
      extensive, progressive, en plaque coating of the brainstem and spinal cord with
      hemangioblastomas developed 1 to 8 years after complete resection of a solitary
      cerebellar hemangioblastoma. Analysis included detailed physical, biochemical,
      radiological, and pathological examinations in all four patients, combined with
      family pedigree analysis. In addition, a detailed investigation of the VHL gene
      was undertaken. Allelic loss, comparative genomic hybridization (CGH), single
      stranded conformational polymorphism screening, CpG island methylation status,
      and X chromosome inactivation clonality analyses were performed. Although there
      was no evidence of germline alterations in the VHL gene on clinical and
      radiological examination or in the family history (all four patients) or analysis
      of peripheral blood (three patients), somatic deletion of one copy of the VHL
      gene occurred in these tumors. These findings indicate that the multiple,
      separate deposits of tumors were likely derived from a single clone. Results of
      CGH indicate that one or several additional genes are probably involved in the
      malignant behavior of the hemangioblastomas in these patients. Furthermore, the
      malignant biological and clinical behavior of these tumors, in which multiple
      sites of subarachnoid dissemination developed 1 to 8 years after initial complete
      resection, followed by progressive tumor growth and death of the patients,
      occurred despite a histological appearance typical of benign hemangioblastomas.
      Malignant hemangioblastomatosis developed 1 to 8 years after resection of an
      isolated cerebellar hemangioblastoma. Alterations of the VHL gene may be
      permissive in this setting, but other genes are likely to be the source of the
      novel biological and clinical presentation of the disseminated hemangioblastomas
      in these patients. This appears to represent a novel condition in which the
      product of one or more mutations in several genes permits malignant tumor
      behavior despite retention of a benign histological picture, a circumstance
      previously not recognized in CNS tumors.

PMID- 11990822
TI  - Endoscope-assisted clipping of a superior hypophyseal artery aneurysm without
      removal of the anterior clinoid process. Case report.
AB  - A 47-year-old man presented with a superior hypophyseal artery aneurysm and an
      ipsilateral posterior communicating artery aneurysm. Both lesions were
      successfully clipped without removal of the anterior clinoid process or
      retraction of the optic nerve by using endoscopic guidance. The endoscope was
      introduced into the prechiasmatic cistern and provided a clear visual field
      around the aneurysm that could not be seen via the operating microscope. The
      endoscope was useful in the identification of the medially projecting lesion and
      the small perforating branches of the ophthalmic segment of the internal carotid
      artery. A fenestrated clip could be introduced around the neck of the aneurysm
      and placed in the best position under endoscopic guidance. Endoscopy-assisted
      clipping is potentially a very useful procedure for aneurysm surgery.

PMID- 11990823
TI  - Adult pial arteriovenous fistula and superior sagittal sinus stenosis:
      angiographic evidence for high-flow venopathy at an atypical location. Case
      report.
AB  - The authors present the case of a 69-year-old man who suffered from bilateral
      cortical venous hypertension due to a brain pial arteriovenous malformation (AVM)
      with a high-flow fistula. The AVM became complicated by the development of a high
      grade stenosis of the posterior superior sagittal sinus (SSS). A comparison of
      cerebral angiograms obtained at different times revealed that the severe SSS
      stenosis had developed within a 5-year period and was located distal to the nidus
      of the left parietal AVM nidus, away from the entrance of the dominant superior
      superficial cortical draining vein into the SSS. The high-flow fistula was
      occluded with detachable coils and the AVM nidus was further embolized with
      acrylic. The SSS stenosis was mechanically dilated by means of balloon
      angioplasty and stent placement. This case provides angiographic evidence to
      support the hypothesis that a pial arteriovenous fistula in an adult can cause
      high-flow occlusive venopathy in a major sinus within a relatively short time and
      that this acquired high-flow occlusive venopathy can develop at an atypical
      location distant from the nidus of the AVM.

PMID- 11990824
TI  - Hearing restoration after resection of an intracanalicular vestibular schwannoma:
      a role for emergency surgery? Case report and review of the literature.
AB  - Patients with vestibular schwannomas (VSs) most commonly present with
      sensorineural hearing loss, which is often insidious or gradual. Up to 26% of
      patients may present with sudden hearing loss, however, which poses an important
      surgical challenge. Sudden hearing loss has been attributed to spasm or occlusion
      of the labyrinthine artery resulting from tumor compression, and it is usually
      treated with corticosteroids. Hearing preservation surgery is not usually
      attempted in patients who have poor or nonserviceable hearing preoperatively. The
      authors describe a 68-year-old man with complete deafness of the left ear since
      childhood, who developed sudden, profound sensorineural hearing loss in the right
      ear. Magnetic resonance imaging revealed a small right-sided intracanalicular
      tumor. Treatment with high-dose corticosteroids produced only minimal improvement
      in hearing. Subsequent emergency decompression and resection of a VS resulted in
      rapid improvement and restoration of hearing, with facial nerve preservation.
      Although most neurotologic lesions in patients with hearing in only one ear are
      managed nonsurgically, resection of small tumors in the setting of sudden hearing
      loss should be considered in selected cases. This finding indicates that a
      therapeutic window may exist during which sudden hearing loss caused by
      intracanalicular tumors is reversible.

PMID- 11990825
TI  - Renal metastasis.

PMID- 11990826
TI  - Malignant schwannoma.

PMID- 11990827
TI  - Thromboprophylaxis.

PMID- 11990828
TI  - Thromboprophylaxis.

PMID- 11990829
TI  - Resection of glioblastoma.

PMID- 11990830
TI  - Resection of glioblastoma.

PMID- 11990831
TI  - Commentary on National Acute Spinal Cord Injury Study III.

PMID- 11990832
TI  - Neurological and functional status 1 year after acute spinal cord injury:
      estimates of functional recovery in National Acute Spinal Cord Injury Study II
      from results modeled in National Acute Spinal Cord Injury Study III.
AB  - OBJECT: In the second National Acute Spinal Cord Injury Study (NASCIS II)
      investigators evaluated several standard neurological parameters but not
      functional activity. This has led to questions concerning the clinical importance
      of the increase in neurological recovery observed following administration of
      methylprednisolone (MP) within 8 hours of acute spinal cord injury (SCI). The
      safety of the therapy has also been questioned. METHODS: Both neurological and
      functional recovery were assessed in NASCIS III, a trial that followed an almost
      identical protocol to NASCIS II. In the current analysis locally weighted
      scatterplot smoothing (LOESS) nonparametric regression is used to model the
      extent of recovery in the Functional Independence Measure (FIM) that is predicted
      by improvement in the NASCIS/American Spinal Cord Injury Association motor scores
      that were documented in NASCIS III 1 year after SCI, and the models are applied
      to the extent of motor recovery demonstrated in NASCIS II. The models predict
      improvement in FIM that would be expected from the motor function recovery
      observed in NASCIS II. Estimates are provided overall and for patients with
      complete and incomplete neurological loss at time of injury. The authors review
      recent evidence obtained from randomized studies documenting adverse effects that
      may result from high-dose MP therapy. The relationship between motor function and
      FIM is strongly nonlinear and dependent on initial level of injury and degree of
      injury severity. In the best statistical model, the expanded motor score could be
      used to explain 77.2% of the variability in the FIM. Based on the mean MP-related
      3.6-unit improvement in the motor score for patients with complete injuries and
      7.3 for those with incomplete injuries owed to MP in NASCIS II, 18.6% of patients
      would improve six or more FIM points and 9% nine or more points, respectively. In
      those with complete neurological injury, the mean motor improvement of 3.6
      predicted that 63.9% of the patients would improve three or more FIM points and
      12.1% six or more points to a maximum of eight points. Of those with incomplete
      neurological injury, a 7.3 mean improvement in motor function predicted that
      27.4% would gain six or more FIM points and that 21% would gain nine or more
      points to a maximum of 15 points. Analysis of the current best evidence from SCI
      and other randomized surgical trials in which high-dose MP has been administered
      provides no grounds for concern about commonly studied adverse effects.
      CONCLUSIONS: The extent of MP therapy-related motor function recovery observed in
      NASCIS II predicted clinically important recovery in the FIM. Reasons to be
      cautious with regard to this prediction include the lack of robustness in
      statistical modeling, some loss of validity in the FIM, and considerable
      heterogeneity in the SCI population. Whatever functional activity is ascribed to
      high-dose MP therapy, it is does not appear to be associated with risk of adverse
      outcomes.

PMID- 11990833
TI  - Complications associated with the prophylactic use of methylprednisolone during
      surgical stabilization after spinal cord injury.
AB  - OBJECT: The authors attempted to determine if there is a significant relationship
      between the incidence of medical complications and the prophylactic use of
      methylprednisolone (MP) during spine surgery in patients with acute spinal cord
      injury (SCI) who had already received MP on hospital admission (typically in the
      setting of an Emergency Room/Trauma Center). METHODS: The authors studied 73
      patients with acute SCI who were admitted to the hospital for at least 7 days
      postinjury. All patients 1) received a 24-hour regimen of MP in the acute period
      of hospitalization; and 2) underwent surgery to stabilize the spine and/or
      decompress the spinal cord. Patients were separated into two groups on the basis
      of whether they received additional MP therapy during spine surgery. A chart
      review was conducted retrospectively to determine the incidence of complications
      up to 6 weeks postinjury. Muscle strength and American Spinal Injury Association
      grades were determined prospectively throughout the follow-up period. In patients
      who received two courses of MP following acute SCI (one at initial
      hospitalization and one during surgery), a significantly increased probability of
      complications was demonstrated compared with those who received no MP therapy
      during surgery. This was particularly evident when the incidences of serious
      complications were compared. CONCLUSIONS: Prophylactic use of MP as a
      neuroprotective agent during spine surgery in patients with acute SCI should be
      avoided in those in whom MP was administered on admission to the hospital.

PMID- 11990834
TI  - Anterior cervical fusion with carbon fiber cage containing coralline
      hydroxyapatite: preliminary observations in 45 consecutive cases of soft-disc
      herniation.
AB  - OBJECT: The purposes of bone substitutes for anterior cervical fusion (ACF) are
      immediate biomechanical support and osteointegration of the graft. The authors
      report their preliminary results in performing ACF in which carbon fiber cages
      (CFCs) containing coralline hydroxyapatite (HA) are used as bone substitute.
      METHODS: During a 24-month period, anterior microsurgical discectomy was
      performed in 45 consecutive patients for soft-disc cervical herniation. In all
      cases ACF was performed using a CFC containing a core of granulated coralline HA.
      Fifty-seven CFCs were implanted in 33 single-level and 12 two-level procedures.
      The mean operative time was 83 minutes for one-level and 97 minutes for two-level
      procedures. The mean hospital stay was 1.51 days, and there were no permanent
      complications. At a mean follow up of 22.3 months, the pain had decreased or
      disappeared in all patients, and the patients' satisfaction rate was very high.
      Good results were also obtained in patients who smoked cigarettes. Patients
      underwent radiographic evaluation at Day 1, and 1, 3, 6, and 12 months
      postoperatively. Implant-related complications were not observed and revision
      surgeries were not performed. Twelve-month cervical x-ray films demonstrated
      complete fusion in all cases, without evidence of breakage, collapse,
      pseudarthrosis, subsidence, angular deformity, or protrusion. Signs of
      pathological absorption and necrosis were not found in contiguous vertebral
      bodies, and inflammatory reactions were never seen around cages. CONCLUSIONS:
      These preliminary results suggest that implants composed of CFC containing
      granulated coralline HA are promising bone substitutes to be used in ACF, with a
      good rate of incorporation and no significant complications.

PMID- 11990835
TI  - Cervical nerve root avulsion in brachial plexus injuries: magnetic resonance
      imaging classification and comparison with myelography and computerized
      tomography myelography.
AB  - OBJECT: The authors describe a new magnetic resonance (MR) imaging technique to
      demonstrate the status of the cervical nerve roots involved in brachial plexus
      injury. They discuss the accuracy and reproducibility of a MR imaging-derived
      classification for diagnosis of nerve root avulsion compared with those of
      myelography combined with computerized tomography (CT) myelography. METHODS: The
      overlapping coronal-oblique slice MR imaging procedure was performed in 35
      patients with traumatic brachial plexus injury and 10 healthy individuals. The
      results were retrospectively evaluated and classified into four major categories
      (normal rootlet, rootlet injuries, avulsion, and meningocele) after confirming
      the diagnosis by surgical exploration with or without spinal evoked potential
      (EP) measurements and by referring to myelography and CT myelography findings.
      The reliability and reproducibility of the MR imaging-based classification was
      prospectively assessed by eight independent observers, and its diagnostic
      accuracy was compared with that of traditional myelography/CT myelography
      classification, correlated with surgical and spinal EP findings in another 50
      cervical roots in 10 patients with traumatic brachial plexus injury. CONCLUSIONS:
      In the retrospective study in which MR imaging and myelography/CT myelography
      findings involving 175 cervical roots in 35 patients were compared, the
      sensitivity of detection of the cervical nerve root avulsion was the same (92.9%)
      with both modalities. In the prospective study, interobserver reliability and
      intraobserver reproducibility showed that there was no statistically significant
      difference between MR imaging and myelography/CT myelography and that their
      accuracy for detecting cervical root avulsion was the same as that in the
      retrospective study. The overlapping coronal-oblique slice MR imaging technique
      is a reliable and reproducible method for detecting nerve root avulsion. The
      information provided by this modality enabled the authors to assess the roots of
      the brachial plexus and provided valuable data for helping to decide whether to
      proceed with exploration, nerve repair, primary reconstruction, or other imaging
      modalities.

PMID- 11990836
TI  - Cervical spine trauma associated with moderate and severe head injury: incidence,
      risk factors, and injury characteristics.
AB  - OBJECT: Diagnosing and managing cervical spine trauma in head-injured patients is
      problematic due to an altered level of consciousness in such individuals. The
      reported incidence of cervical spine trauma in head-injured patients has
      generally ranged from 4 to 8%. In this retrospective study the authors sought to
      define the incidence of cervical injury in association with moderate or severe
      brain injury, emphasizing the identification of high-risk patients. METHODS: The
      study included 447 consecutive moderately (209 cases) or severely (238 cases)
      head injured patients who underwent evaluation at two Level 1 trauma centers over
      a 40-month period. Of the 447 patients, 24 (5.4%) suffered a cervical spine
      injury (17 men and seven women; mean age 39 years; median Glasgow Coma Scale
      [GCS] score of 6, range 3-14). Of these 24 patients, 14 (58.3%) sustained spinal
      cord injuries (SCIs), 14 sustained injuries in the occiput-C3 region, and 10
      underwent a stabilization procedure. Of the 14 patients with SCIs, nine
      experienced an early hypotensive and/or hypoxic insult. Regarding the mechanism
      of injury, cervical injuries occurred in 21 (8.2%) of 256 patients involved in
      motor vehicle accidents (MVAs), either as passengers or pedestrians, compared
      with three (1.6%) of 191 patients with non-MVA-associated trauma (p < 0.01). In
      the subset of 131 MVA passengers, 13 (9.9%) sustained cervical injuries. Patients
      with an initial GCS score less than or equal to 8 were more likely to sustain a
      cervical injury than those with a score higher than 8 (odds ratio [OR] 2.77, 95%
      confidence interval [CI] = 1.11-7.73) and were more likely to sustain a cervical
      SCI (OR 5.5, 95% CI 1.22-24.85). At 6 months or more postinjury, functional
      neurological recovery had occurred in nine patients (37.5%) and eight (33.3%) had
      died. CONCLUSIONS: Head-injured patients sustaining MVA-related trauma and those
      with an initial GCS score less than or equal to 8 are at highest risk for
      concomitant cervical spine injury. A disproportionate number of these patients
      sustain high cervical injuries, the majority of which are mechanically unstable
      and involve an SCI. The development of safer and more rapid means of determining
      cervical spine integrity should remain a high priority in the care of head
      injured patients.

PMID- 11990837
TI  - Surgical treatment of lumbar stenosis in achondroplasia.
AB  - OBJECT: The authors conducted a study to evaluate the results of a unique
      surgical procedure for treating primary lumbar stenosis in patients with
      achondroplasia, based on its distorted anatomical dimensions. METHODS: A
      consecutive single-center series of 36 achondroplastic dwarfs with symptomatic
      lumbar stenosis underwent dynamic lumbar myelography to determine the most
      stenotic lumbar segment. This level was surgically decompressed by selective
      widening of the lumbar interapophyseolaminar diameter; laminectomy was not
      performed. The L2-3 level was decompressed in 97% of the cases and the L1-2 and
      L3-4 levels in 58 and 61%, respectively. Lower lumbar levels were rarely affected
      by stenosis. Stenosis typically did not occur at the level of the lamina, where
      the pseudoscalloping of the vertebral body compensates for the spinal narrowing,
      obviating the need for laminectomy. Complete relief of symptoms was demonstrated
      in 25 (71.4%) of 35 patients. Tolerable disease remained in eight patients
      (22.9%) postoperatively. In two cases (5.7%) surgery resulted in no benefit. One
      case was lost to follow up. The presence of a lumbar epidural hematoma
      complicated one procedure. CONCLUSIONS: In this series the interapophyseolaminar
      decompression was demonstrated to be an effective and safe procedure for the
      treatment of symptomatic stenosis in achondroplasia. The upper lumbar segments,
      particularly the L2-3 level, were most frequently involved. Dynamic lumbar
      myelography proved mandatory in demonstrating the symptomatic level.

PMID- 11990838
TI  - Autotransfusion by cell saver technique in surgery of lumbar and thoracic spinal
      fusion with instrumentation.
AB  - OBJECT: The authors used a modern cell saver technique to perform autotransfusion
      in patients undergoing instrument-assisted lumbar and/or thoracic spinal fusion,
      in whom significant blood loss was anticipated. The safety and benefits of this
      procedure as well as its cost effectiveness were analyzed. METHODS: The authors
      studied 50 patients who underwent lumbar and/or thoracic spinal fusion in which
      instrumentation was placed between January 1998 and June 2000 and in whom an
      estimated blood loss of 500 ml or more was expected. All surgeries were conducted
      by a single neurosurgeon (D.R.S.). During surgery, the Brat 2 cell saver system
      was used to salvage the autologous blood. The anesthesiologist and surgeon
      jointly decided, on the basis of hematocrit and clinical stability, whether
      transfusion was necessary in each patient. Various parameters (hematocrit, plasma
      and urine hemoglobin, platelet counts, coagulation profile, and serum bilirubin)
      were measured pre-, intra-, and postoperatively. Thirty-three patients (66%)
      required transfusion. The mean blood loss in these patients was 1046 ml. The most
      important factor affecting blood loss was the number of levels fused (p <
      0.0001). Only two patients required postoperative homologous transfusion. The
      mean decrease in hematocrit was 7.82%. The maximum reduction of platelet count
      was limited to 80,000/mm3. Major complications such as hemoglobinuria,
      coagulopathy, cardiopulmonary problems, air embolism, and major sepsis were not
      observed in this study. CONCLUSIONS: Autotransfusion performed using a modern
      cell saver technique is safe and has many advantages over homologous transfusion.
      It conserves the homologous blood resources. The costs of the two modes are
      statistically comparable when greater than 500 ml of red blood cell transfusion
      is necessary.

PMID- 11990839
TI  - Thoracoscopic resection of thoracic neurogenic tumors.
AB  - OBJECT: The authors describe the treatment and results of thoracoscopic resection
      performed in patients with neurogenic tumors. METHODS: Seven patients with large
      intrathoracic paraspinal neurogenic tumors underwent a thoracoscopic procedure to
      achieve gross-total resection. All tumors were entirely intrathoracic and treated
      thoracoscopically except in one patient whose tumor had an intraspinal extension.
      Gross-total resection was achieved in all cases. Postoperatively, one patient
      developed Homer syndrome. The only other complication, transient intercostal
      neuralgia, resolved in all patients. Clinical examination and magnetic resonance
      imaging follow-up examination in all patients demonstrated no evidence of
      recurrent disease (mean follow up 12.5 months). CONCLUSIONS: Endoscopic
      transthoracic approaches can reduce approach-related soft-tissue morbidity and
      facilitate a patient's recovery by preserving the normal tissues of the chest
      wall, by avoiding rib retraction and muscle transection, and by reducing
      postoperative pain.

PMID- 11990840
TI  - Increased pedicle screw pullout strength with vertebroplasty augmentation in
      osteoporotic spines.
AB  - OBJECT: The authors conducted a biomechanical study to evaluate pedicle screw
      pullout strength in osteoporotic cadaveric spines. Nonaugmented hemivertebrae
      were compared with pressurized polymethylmethacrylate (PMMA)-augmented
      hemivertebrae. METHODS: Six formalin-fixed cadaveric thoracolumbar spines at
      least two standard deviations below the mean bone mineral density (BMD) for age
      were obtained. Radiographic and BMD studies were correlated to grades I, II, and
      III osteoporosis according to the Jekei scale. Each of the 21 vertebrae underwent
      fluoroscopic placement of 6-mm transpedicular screws with each hemivertebra
      serving as the control for the contralateral PMMA-augmented hemivertebra. Pedicle
      screws were then evaluated for biomechanical axial pullout resistance. Augmented
      hemivertebrae axial pullout forces were increased (p = 0.0005). The mean increase
      in pullout force was 181% for Grade I, 206% for Grade II, and 213% for Grade III
      osteoporotic spines. Augmented Grade I osteoporotic spines demonstrated axial
      pullout forces near those levels reported in the literature for nonosteoporotic
      specimens. Augmented Grade II osteoporotic specimens demonstrated increases to
      levels found in nonaugmented vertebrae with low-normal BMD. Augmented Grade III
      osteoporotic specimens had increases to levels equal to those found in
      nonaugmented Grade I vertebrae. CONCLUSIONS: Augmentation of osteoporotic
      vertebrae in PMMA-assisted vertebroplasty can significantly increase pedicle
      screw pullout forces to levels exceeding the strength of cortical bone. The
      maximum attainable force appears to be twice the pullout force of the
      nonaugmented pedicle screw for each osteoporotic grade.

PMID- 11990841
TI  - Biomechanical comparison of four anterior atlantoaxial plate systems.
AB  - OBJECT: The optimum fixation method to achieve atlantoaxial fusion after
      resection of the odontoid process remains a matter of discussion. Anterior
      atlantoaxial plate fixation has been described by Harms as a fixation procedure
      to be performed after transoral odontoid resection. In recent biomechanical and
      clinical studies investigators have shown that this procedure is a good
      alternative to established posterior atlantoaxial fixation techniques, but they
      have also indicated the biomechanical disadvantages of the Harms plate design.
      Therefore, three new anterior atlantoaxial plate designs were developed. The
      purpose of this study was to compare these three newly designed plate systems
      biomechanically with that used in Harms anterior atlantoaxial plate fixation.
      METHODS: Twenty-four human craniocervical cadaveric specimens were tested in
      flexion, extension, axial rotation, and lateral bending in a nonconstrained
      testing apparatus by using a nondestructive stiffness method. Three-dimensional
      displacement of C 1-2 was measured with an optical measurement system. Six
      different groups were examined: 1) control (24 specimens); 2) unstable (after
      odontoidectomy and dissection of the atlantoaxial ligaments; 24 specimens); 3)
      Harms (anterior atlantoaxial plate fixation according to Harms; six specimens);
      4) subarticular atlantoaxial plate (SAAP; six specimens); 5) transpedicular
      atlantoaxial plate (TAAP; six specimens); and 6) subarticular atlantoaxial
      locking plate (SAALP; six specimens). Stiffness, range of motion, and neutral and
      elastic zones were determined. Compared with the Harms plate, stiffness was
      significantly higher when methods for placing the SAAP, TAAP, and SAALP devices
      were used (p < 0.05). Angular displacement of SAALPs was less than that
      demonstrated in any other group (p < 0.05). Stiffness values in any direction
      were significantly greater for the SAALP-fixed specimens than for the TAAP, SAAP,
      Harms, control, or unstable specimens (p < 0.05). CONCLUSIONS: Experimentally,
      the SAAP, TAAP, and Harms plate achieved less stable fixation than the SAALP.
      Therefore, if transoral odontoid resection is performed, SAALP-fixed spines will
      provide significantly improved stability compared with previous fixation devices
      and methods. This may be a necessary prerequisite for a fast and uneventful
      osseous fusion even without additional posterior stabilization.

PMID- 11990842
TI  - Influence of cage design on interbody fusion in a sheep cervical spine model.
AB  - OBJECT: The purpose of this study was to compare the characteristics of interbody
      fusion achieved using an autologous tricortical iliac crest bone graft with those
      of a cylinder- and a box-design cage in a sheep cervical spine model. This study
      was designed to determine whether there are differences between three interbody
      fusion procedures in: 1) ability to preserve postoperative distraction; 2)
      biomechanical stability; and 3) histological characteristics of intervertebral
      bone matrix formation. METHODS: Twenty-four sheep underwent C3-4 discectomy and
      fusion in which the following were used: Group 1, autologous tricortical iliac
      crest bone graft (eight sheep); Group 2, titanium cylinder-design cage filled
      with autologous iliac crest bone graft (eight sheep); and Group 3, titanium box
      design cage filled with autologous iliac crest graft (eight sheep). Radiography
      was performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the
      same time points, disc space height, intervertebral angle, and lordosis angle
      were measured. After 12 weeks, the sheep were killed, and fusion sites were
      evaluated by obtaining functional radiographs in flexion and extension.
      Quantitative computerized tomography scans were acquired to assess bone mineral
      density, bone mineral content, and bone callus volume. Biomechanical testing was
      performed in flexion, extension, axial rotation, and lateral bending. Stiffness,
      range of motion, neutral zone, and elastic zone were determined.
      Histomorphological and histomorphometric analyses were performed, and polychrome
      sequential labeling was used to determine the time frame of new bone formation.
      Over a 12-week period significantly higher values for disc space height and
      intervertebral angle were shown in cage-treated sheep than in those that received
      bone graft. Functional radiographic assessment revealed significantly lower
      residual flexion-extension movement in sheep with the cylinder cage-fixed spines
      than in those that received bone graft group. The cylinder-design cages showed
      significantly higher values for bone mineral content, bone callus content, and
      stiffness in axial rotation and lateral bending than the other cages or grafts.
      Histomorphometric evaluation and polychrome sequential labeling showed a more
      progressed bone matrix formation in the cylindrical cage group than in both other
      groups. CONCLUSIONS: Compared with the tricortical bone graft, both cages showed
      significantly better distractive properties. The cylindrical cage demonstrated a
      significantly higher biomechanical stiffness and an accelerated interbody fusion
      compared with the box-design cage and the tricortical bone graft. The differences
      in bone matrix formation within both cages were the result of the significantly
      lower stress shielding on the bone graft by the cylinder-design cage.

PMID- 11990843
TI  - Traumatic thoracic spinal fracture dislocation with minimal or no cord injury.
      Report of four cases and review of the literature.
AB  - OBJECT: Thoracic fracture dislocations reportedly lead to complete paraplegia in
      80% of cases. It is rare for these dislocations not to cause neurological
      deficits, as evidenced by the mere 11 well-documented neurologically intact cases
      in the English-language literature. METHODS: The authors report four cases of
      thoracic fracture dislocation that remained neurologically intact and discuss 11
      other previously published well-documented cases. Overall there were 10 men and
      five women with a mean age of 34 years (range 17-66 years). Mechanisms of injury
      included car crash in six, motorcycle crash in seven, plane crash in one, and
      fall from a horse in one. On admission, neurological deficits were absent in 11
      patients, intercostal neuralgia was present in two, and mild lower-extremity
      weakness/numbness was demonstrated in two. All suffered significant thoracic
      pain, with 14 patients having sustained rib fractures and eight a hemothorax. The
      levels of dislocation were T3-4 in two, T5-6 in four, T6-7 in four, T7-8 in two,
      T8-9 in one, and T9-10 in two. All suffered some degree of lateral translation
      (mean 12 mm, range 3-27 mm). There were six cases of well-documented anterior
      subluxation in addition to translation (mean 12 mm, range 4-23 mm), and all
      involved some degree of fracture imploding of one vertebral body (VB) into an
      adjacent VB. There were six cases of burst fracture with translation (mean
      kyphotic angle 38 degrees, range 28-50 degrees). Bilateral pedicle shear
      fractures were present in all 15 cases at the site of subluxation, thus
      separating the anterior from the posterior elements and preserving the spinal
      canal. Only two of the 15 patients suffered complete spondylolisthesis. Five
      patients underwent successful nonoperative management with prolonged bed rest; at
      follow-up examination, neurological status remained normal in all five, lesions
      were radiographically unchanged in three, and there was less subluxation but not
      anatomical alignment in two. Ten patients underwent successful internal fixation
      via anterior approaches (two cases), posterior approaches (five cases), and
      combined approaches (three cases). Neurological status either improved to normal
      or remained normal except in one case with persistent intercostal neuralgia.
      Surgery resulted in no change in alignment in three, improved but not anatomical
      alignment in 11, and normal alignment in one patient. All patients ambulated
      unassisted by 6 months. CONCLUSIONS: In cases in which bilateral pedicle
      fractures occur at the site of significant thoracic subluxation and/or
      translation, preservation of the spinal canal and spinal cord neurological
      function can rarely occur when both the lamina and spinal cord do not dislocate
      along with the anterior VBs. In these instances, perfect anatomical reduction may
      require forces that unnecessarily put neurological function at risk and the
      results appear to justify internal fixation with some or no reduction of
      deformity.

PMID- 11990844
TI  - Avulsion transverse ligament injuries in children: successful treatment with
      nonoperative management. Report of three cases.
AB  - Neck injuries in children most commonly affect the upper cervical spine. Injuries
      of the transverse ligament and its attachments may result in C1-2 instability,
      but the optimum form of treatment is unknown. Three patients, who ranged in age
      from 5 to 11 years, sustained transverse atlantal ligament injuries with
      unilateral avulsion fracture of the osseous tubercle of C-1. One child was
      injured in a fall and two were involved in motor vehicle accidents. Although all
      patients presented with neck pain, none exhibited neurological deficits. Plain
      radiography demonstrated no evidence of osseous injury, but an increased
      predental interval was noted in each case. Computerized tomography (CT) scanning
      demonstrated the avulsion fractures, and magnetic resonance imaging revealed
      evidence of soft-tissue injuries in the occipital-C2 ligamentous complex. All
      children were managed with external immobilization (halo vest in two and a Sterno
      Occipito-Mandibular Immobilizer brace in one), for 6 to 12 weeks. Follow-up CT
      scanning demonstrated reattachment of the avulsed osseous tubercle, and dynamic
      cervical spine radiographs revealed the absence of C1-2 instability. The results
      of these cases suggest a role for external immobilization in the treatment of
      osseous avulsion injuries of the transverse atlantal ligament in children.

PMID- 11990845
TI  - Spontaneous intracranial hypotension due to thoracic disc herniation. Case
      report.
AB  - Spontaneous intracranial hypotension is frequently idiopathic. The authors report
      on a patient presenting with symptomatic intracranial hypotension caused by a
      transdural calcified thoracic disc herniation. Cranial magnetic resonance (MR)
      imaging revealed classic signs of intracranial hypotension, and a combination of
      spinal MR and computerized tomography myelography confirmed a mid-thoracic
      transdural calcified herniated disc as the cause. The patient was treated with an
      epidural blood patch and burr hole drainage of the subdural effusion on two
      occasions. Postoperatively the headache resolved and there was no neurological
      deficit. Thoracic disc herniation may be a cause of spontaneous intracranial
      hypotension.

PMID- 11990846
TI  - Dual-strap augmentation of a halo orthosis in the treatment of atlantooccipital
      dislocation in infants and young children. Technical note.
AB  - Two children who were 13 months and 3 years old and who had suffered traumatic
      atlantooccipital dislocation were each treated by being placed in a halo orthosis
      for 10 weeks. Because of a continued loss of reduction due to the poor fit of the
      halo vest, a dual-strap augmentation was developed. This strap augmentation
      allowed consistent reduction to be maintained. Both children were therefore
      successfully treated nonsurgically with a halo vest. One child remained
      neurologically intact and the other had improvement in motor strength. There were
      no complications from the use of strap augmentation for halo vest fixation.

PMID- 11990847
TI  - Fracture dislocation of the neurocentral synchondroses of the axis. Case
      illustration.

PMID- 11990848
TI  - Spontaneous spinal hemorrhage during scuba diving. Case illustration.

PMID- 11990849
TI  - History of spinal disorders and Cerrahiyetul Haniye (Imperial Surgery): a review
      of a Turkish treatise written by Serefeddin Sabuncuoglu in the 15th century.
      Historical vignette.
AB  - The history of spinal surgery represents an important aspect of spine-related
      sciences. The development of the treatment strategies of spine-related disorders
      has predominantly been recorded in the Western literature. In this paper, a
      Turkish physician, Serefeddin Sabuncuoglu (1385-1468), and his treatise,
      Cerrahiyetul Haniye (Imperial Surgery), are presented. Three sections of this
      book regarding spinal disorders (spinal dislocations, sciatica, and back pain)
      are reviewed. The techniques described were used by Sabuncuoglu in the 1400s. In
      conclusion, the language and illustrations of this treatise are unique. Compared
      with current approaches, there are no major differences in the principles of
      treating spinal traumas despite the passage of almost 500 years.

PMID- 11990850
TI  - Spondylolisthesis.

PMID- 11990851
TI  - Sympathectomy.

PMID- 11990852
TI  - Spinal cord herniation.

PMID- 11990853
TI  - New functions for the matrix metalloproteinases in cancer progression.
AB  - Matrix metalloproteinases (MMPs) have long been associated with cancer-cell
      invasion and metastasis. This provided the rationale for clinical trials of MMP
      inhibitors, unfortunately with disappointing results. We now know, however, that
      the MMPs have functions other than promotion of invasion, have substrates other
      than components of the extracellular matrix, and that they function before
      invasion in the development of cancer. With this knowledge in hand, can we
      rethink the use of MMP inhibitors in the clinic?

PMID- 11990854
TI  - Multiple myeloma: evolving genetic events and host interactions.
AB  - Multiple myeloma is a neoplasm of terminally differentiated B cells (plasma
      cells) in which chromosome translocations frequently place oncogenes under the
      control of immunoglobulin enhancers. Unlike most haematopoietic cancers, multiple
      myeloma often has complex chromosomal abnormalities that are reminiscent of
      epithelial tumours. What causes full-blown myeloma? And can our molecular
      understanding of this common haematological malignancy be used to develop
      effective preventive and treatment strategies?

PMID- 11990855
TI  - DNA and its associated processes as targets for cancer therapy.
AB  - DNA is the molecular target for many of the drugs that are used in cancer
      therapeutics, and is viewed as a non-specific target of cytotoxic agents.
      Although this is true for traditional chemotherapeutics, other agents that were
      discovered more recently have shown enhanced efficacy. Furthermore, a new
      generation of agents that target DNA-associated processes are anticipated to be
      far more specific and effective. How have these agents evolved, and what are
      their molecular targets?

PMID- 11990856
TI  - Molecular mechanisms of cancer pain.
AB  - Pain is the most disruptive influence on the quality of life of cancer patients.
      Although significant advances are being made in cancer treatment and diagnosis,
      the basic neurobiology of cancer pain is poorly understood. New insights into
      these mechanisms are now arising from animal models, and have the potential to
      fundamentally change the way that cancer pain is controlled.

PMID- 11990857
TI  - Emerging molecular markers of cancer.
AB  - Alterations in gene sequences, expression levels and protein structure or
      function have been associated with every type of cancer. These 'molecular
      markers' can be useful in detecting cancer, determining prognosis and monitoring
      disease progression or therapeutic response. But what is the best way to identify
      molecular markers and can they be easily incorporated into the clinical setting?

PMID- 11990858
TI  - Oncogenic resistance to growth-limiting conditions.
AB  - Many carcinogens are mutagens, indicating that mutagenesis is the driving force
      of carcinogenesis. But what if we turn this prevailing view on its head? I will
      argue here that carcinogens are cytostatic and/or cytotoxic, and it is not
      mutation per se, but clonal selection for resistance to these antiproliferative
      conditions, that leads to cancer. But why aren't all cytotoxins carcinogenic?

PMID- 11990859
TI  - Breast cancer activism: past lessons, future directions.
AB  - Breast cancer activism has become a fixture in the United States, where
      fundraising events are ubiquitous and government financing of research into the
      disease has skyrocketed. Activists in other countries are now reporting similar
      accomplishments. Here, predominantly using the United States as a case study, I
      analyse the recent successes of breast cancer activism. I also raise a series of
      questions about the future goals of activism.

PMID- 11990860
TI  - History of haematopoietic stem-cell transplantation.
AB  - After fifty years of investigations into the use of pluripotent haematopoietic
      stem-cell transplantation for cancer therapy, this procedure has progressed from
      one that was thought to be plagued with insurmountable complications to a
      standard treatment for many haematological malignancies. How have these hurdles
      been overcome, and how can the therapy be expanded to include patients who are
      too old or medically infirm to tolerate conventional transplant approaches?

PMID- 11990861
TI  - Clinical features of psoriatic arthritis.
AB  - The past 5 years have seen major advances in understanding the immunology and
      molecular biology of psoriatic arthritis (PsA), especially the impact of
      cytokines such as tumor necrosis factor (TNF), which has produced striking, long
      term benefits in patients with rheumatoid arthritis (RA). Because PsA is not the
      same disease as RA, the ability to distinguish between them is important to
      physicians in managing patients who have clinical features consistent with an
      arthropathy. The development of TNF inhibitors directed specifically at the
      mechanisms of skin and joint inflammation offers hope to patients who suffer from
      the debilitating effects of PsA.

PMID- 11990862
TI  - Current perspectives in the recognition and management of psoriatic arthritis:
      implications for integrated patient care.
AB  - Psoriatic arthritis (PsA), a chronic and debilitating spondyloarthropathy, is
      believed to affect as many as 30% of those with psoriasis. The use of tumor
      necrosis factor (TNF) inhibitors shows promise in the treatment of PsA and
      psoriasis. Etanercept, the first TNF inhibitor to be approved for use in PsA,
      inhibits the proinflammatory cytokine TNF in both conditions, making it possible
      for the clinician to prescribe a single agent to manage both the joint
      manifestations of PsA and the cutaneous manifestations of psoriasis. Etanercept
      has been shown to be well tolerated, even for long-term use, and is potentially
      superior to disease-modifying antirheumatic drugs.

PMID- 11990863
TI  - Etanercept: a new era in the treatment of psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) can exact a devastating physical and emotional toll
      from its sufferers. For decades, patients have been understandably dismayed by
      the shortcomings of the therapeutic approaches that have been available. Now,
      equipped with a greater understanding of the role of cytokines such as tumor
      necrosis factor in the origins of PsA, researchers have been able to develop
      cytokine inhibitors aimed precisely at the mechanisms of cutaneous and articular
      inflammation. When used in combination with physical rehabilitation,
      pharmacologic therapy can slow or arrest the progression of PsA and profoundly
      improve the quality of life of PsA patients.

PMID- 11990864
TI  - Etanercept and its implications for managed care.
AB  - Etanercept, a new drug for psoriatic arthritis (PsA), offers a safe and
      effective, but somewhat costly treatment for a condition for which therapeutic
      options have been scarce. Its debut poses a challenge to managed care
      organizations in terms of its potentially adverse impact on the pharmacy budget.
      Managed care organizations must take the initiative in developing appropriate
      criteria for authorizing the use of etanercept and in overseeing the management
      and reimbursement of various treatments for PsA. Care is warranted in evaluating
      the options to take into account the clinical, human, and financial ramifications
      of their use.

PMID- 11990865
TI  - Selective suppression of chemokine receptor CXCR3 expression by interferon-beta1a
      in multiple sclerosis.
AB  - We studied the expression of chemokine receptors CCR1, CCR2, CCR3, CCR5, and
      CXCR3 on CD4 and CD8 positive T cells, and on CD14 positive monocytes in blood
      from 10 patients with relapsing-remitting multiple sclerosis (MS) at initiation
      of interferon (IFN)-beta treatment, after 1 month and after 3 months of
      treatment. It was found that the expression of CXCR3 on CD4+ and CD8+ T cells was
      significantly reduced after 3 months of treatment. The expression of other
      receptors was unaltered. Since CXCR3 cells are enriched in cerebrospinal fluid
      (CSF), and are detected in lesion material in MS this may represent an important
      mode of action of interferon-beta in MS.

PMID- 11990866
TI  - Two-year follow-up study of primary and transitional progressive multiple
      sclerosis.
AB  - This study documents changes in clinical and magnetic resonance imaging (MRI)
      characteristics in a large cohort of patients with primary and transitional
      progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and
      TPMS were recruited from six European centres and underwent clinical and MRI
      examination at three time points: baseline, year one and year two. Of the 190
      patients recruited clinical data were available on 125 patients (66%, five
      centres) and MRI data were available on 113 patients (59%, four centres) at 2
      years. Significant increases were seen in T2 load and T1 hypointensity, while
      brain and cord volume decreased. In PPMS significantly higher lesion loads were
      found in those who presented with non-cord syndromes when compared to cord
      presentation and there was a trend to greater brain atrophy in those who
      deteriorated clinically over the course of the study compared to those who
      remained stable. Significant cord atrophy was only seen in those with a cord
      presentation. Measurable changes in MRI parameters can be detected in PPMS
      patients over a relatively short period of time. MRI quantification is likely to
      be useful in elucidating disease mechanisms in PPMS and in the execution of
      clinical trials.

PMID- 11990867
TI  - Prospective study of multiple sclerosis with early onset.
AB  - Fifty-four subjects (36 females and 18 males) affected by clinically definite
      multiple sclerosis (MS) and with onset of the disease at 15 years of age or
      before were prospectively studied in five Italian MS centres. Female/male ratio
      was 4.7 in subjects with age > or = 12 years, suggesting a role of hormonal
      changes in triggering MS onset The mean follow-up duration was 10.9+/-5.6 years.
      The functional systems more frequently involved at onset were the pyramidal and
      brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects
      (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing
      progressive in 15 (28%). Disability was assessed by the Expanded Disability
      Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (+/-2.5).
      The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, >6 in 24% of
      cases. Disability after 8 years was highly predicted by disability in the first
      year (p=0.008). There was a tendency to a worse prognosis in relation to the
      number of relapses in the first 2 years (p=0.08). The outcome was not influenced
      by the characteristics of symptoms at onset age and gender.

PMID- 11990868
TI  - MRI brain volume changes in relapsing-remitting multiple sclerosis patients
      treated with interferon beta-1a.
AB  - The aim of this study was to investigate changes of brain volume as measured by
      magnetic resonance imaging (MRI) in relapsing-remitting multiple sclerosis (MS)
      patients under treatment with interferon beta-1a. Moreover, the relationship
      between brain volume changes and standard MR or clinical outcome variables was
      determined. After a 6-month pretreatment period, 52 patients with relapsing
      remitting MS were assigned to receive interferon beta-1a (Rebif-Serono) during a
      24-month treatment period MRI scans were performed monthly during the 6-month
      pretreatment period and for the first 9 months of the treatment period. A final
      MRI scan was also performed at the end of the 12- and 24-month treatment period.
      Over 24 months of IFNbeta-1a treatment, a significant decrease of hyperintense
      lesion volume was found (-18.0%; p<0.0001) compared to the last pretreatment
      scan, while T1 hypointense volume showed a slight nonsignificant increase
      (+2.2%), and brain volume showed a significant decrease (-2.2%; p<0.0001). The
      mean volume of enhancing lesions over the 6-month pretreatment period was
      significantly related to absolute (p=0.02; r=-0.32) and per cent change (p=0.03;
      r=-0.30) of brain volume during 24-month treatment period. No correlations
      between changes in brain volume and changes in T2 hyperintense volume or T1
      hypointense volume were observed. Neither was there a relationship between brain
      volume and changes of Expanded Disability Status Scale (EDSS) or frequency in
      clinical relapses. Of the group in whom was detected a significant decrease of
      brain volume, 13 out of 26 (50%) had a sustained change in EDSS while in the
      group that did not have a significant decrease of brain volume, only 3 out of 26
      (11.5%) had a sustained EDSS change (p=0.02). In this study a decrease of brain
      volume was found in relapsing-remitting MS patients treated with IFNbeta-1a over
      2 years. The only parameter that predicted brain volume decrease by 2 years of
      IFNbeta-1a treatment was the mean volume of enhancing lesions over the 6-month
      pretreatment period.

PMID- 11990869
TI  - Interferon-beta-1b and interferon-gamma have similar inhibitory effects on
      apolipoprotein-E production in the monocyte/macrophage.
AB  - Apolipoprotein-E (Apo-E) is the major lipid carrier in the brain, and is
      therefore important in the recyding of lipids and cholesterol to regenerating
      neurons during the remission phase of multiple sclerosis (MS). Interferon (IFN)
      gamma has been shown to inhibit Apo-E production by a mainly post-transcriptional
      method in a macrophage cell line, and reduced Apo-E in cerebrospinal fluid is
      noted during the remission phase in patients. IFN-beta-1b is a recombinantly
      produced, anti-inflammatory cytokine, which has been shown to reduce the severity
      of MS relapses and reduce relapse rate. We have examined the effects of IFN-gamma
      and IFN-beta-1b on the production of Apo-E mRNA, cellular protein and secreted
      protein in primary monocytes derived from donor blood. IFN-beta-1b does not
      relieve the dose-dependent inhibition of Apo-E seen with IFN-gamma at up to 100
      U/ml in these cells, and when used alone inhibits Apo-E production in a dose
      dependent manner. This inhibition by IFN-beta-1b was seen to be at a
      transcriptional level, and dose dependent up to 100 U/ml. Apo-E genotype, which
      has also been linked to failure to recover from MS relapses, did not affect this
      inhibition. The mode of action of IFN-beta-1b in MS is therefore not thought to
      be through modification of Apo-E production.

PMID- 11990870
TI  - Paclitaxel (Taxol) attenuates clinical disease in a spontaneously demyelinating
      transgenic mouse and induces remyelination.
AB  - Treatment with paclitaxel by four intraperitoneal injections (20 mg/kg) 1 week
      apart attenuated clinical signs in a spontaneously demyelinating model, if given
      with onset of clinical signs. If given at 2 months of age (1 month prior to
      clinical signs), disease was almost completely prevented The astrogliosis,
      prominent in our model, was reversed by paditaxel as determined by astrocyte
      counts and quantitation of GFAP. Electron microscopic examination of affected
      regions at 2.5 months demonstrated that the myelin was generally normal. By 4
      months of age, demyelination was common in the superior cerebellar peduncle,
      maximal at 6 months, but continued to 8 months. In addition to myelin vacuolation
      and nude axons, the presence of many thin myelin sheaths suggested remyelination
      or partial demyelination. Although no evidence of oligodendrocyte loss was seen,
      nuclear changes were observed. To substantiate that remyelination was occurring,
      we measured MBP (18.5 kDa), MBP-exon II, Golli-MBP, TP8, Golli-MBP-J37, platelet
      derived growth factor alpha (PDGFR alpha) and sonic hedgehog (SHH). Of these TP8,
      PDGFR alpha and SHH were up-regulated in the untreated transgenic. After
      paditaxel treatment, MBP-Exon II, TP8, PDGFR alpha and SHH were further up
      regulated. We concluded that some of the effects of paditaxel were to stimulate
      proteins involved in early myelinating events possibly via a signal transduction
      mechanism.

PMID- 11990871
TI  - Results of an international questionnaire on immunosuppressive treatment of
      multiple sclerosis.
AB  - In November 2000, a questionnaire was sent to 702 multiple sclerosis (MS)
      centers. Data on the institute, treating neurologists, number of MS patients
      under care, and the number of patients treated with immunosuppressive treatments
      were collected. The results indicate that overall, around 10% of MS patients are
      treated with one of four drugs: azathioprine, cyclophosphamide, methotrexate, and
      mitoxantrone. Azathioprine was most frequently used. More than 30% of MS patients
      in France are treated with immunosuppressive drugs. In some other countries,
      these treatments are hardly prescribed.

PMID- 11990872
TI  - Treatment of multiple sclerosis with cyclophosphamide: critical review of
      clinical and immunologic effects.
AB  - Cyclophosphamide is an alkylating agent used to treat malignancies and immune
      mediated inflammatory non-malignant processes such as lupus nephritis and immune
      mediated neuropathies. It has been studied as a treatment for multiple sclerosis
      (MS) for the past 30 years and is used by physicians in selected cases of
      progressive or worsening MS. Review of published reports suggests that it is
      efficacious in cases of worsening MS that have an inflammatory component as
      evidenced by relapses and/or gadolinium (Gd)-enhancing lesions on magnetic
      resonance imaging (MRI) or in patients in earlier stages of disease where
      inflammation predominates over degenerative processes in the central nervous
      system (CNS). There is no evidence of efficacy in primary progressive MS or later
      stages of secondary progressive MS. Although a general immunosuppressant that
      affects both T- and B-cell function, cyclophosphamide has selective immune
      effects in MS by suppressing IL-12 and Th1-type responses and enhancing Th2/Th3
      responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Side effects
      include nausea, alopecia, infertility, bladder toxicity and risk of malignancy.
      The most commonly used regimens involve every 4- to 8-week outpatient i.v. pulse
      therapy given with or without corticosteroids and are usually well-tolerated by
      patients. Cyclophosphamide is currently used in patients whose disease is not
      controlled by beta-interferon or glatiramer acetate and those with rapidly
      worsening MS.

PMID- 11990873
TI  - Stem cell transplantation in multiple sclerosis: multiple choices and multiple
      challenges.
AB  - Multiple sclerosis (MS) is generally considered as an autoimmune disease of the
      central nervous system. This concept has led to the idea that profound
      immunosuppression followed by transplantation of stem cell grafts would stop, or
      at least slow down, disease activity. Supported by the positive effects of
      hematopoietic stem cell transplantation (HSCT) on experimental autoimmune
      encephalomyelitis and by anecdotal reports on the beneficial effect of HSCT on MS
      patients with concomitant malignant disease, HSCT programs for MS have been
      initiated worldwide. At this stage, it is impossible to draw general conclusions
      from the preliminary data reported and therefore overenthusiastic expectations
      should be tempered. The follow-up periods are too short the groups are too small,
      the selected patients and protocols too heterogeneous, and publication bias on
      positive results cannot be excluded. However, there is ample evidence that HSCT
      is a technically feasible approach in MS, not more dangerous than in the hemato
      oncological diseases. For every step in the HSCT procedure, there are many
      different options. The time has come for a systematic analysis of the safety and
      efficacy associated with the different methodologies.

PMID- 11990874
TI  - Effects of a short-term exercise training program on aerobic fitness, fatigue,
      health perception and activity level of subjects with multiple sclerosis.
AB  - Multiple sclerosis (MS) patients of an inpatient rehabilitation program have been
      randomly assigned to an exercise training (MS-ET) or nontraining group (MS-NI).
      Before and after 4 weeks of aerobic exercise training, a graded maximal exercise
      test with measurement of gas exchange and a lung function test was administered
      to all 26 patients fulfilling the inclusion criteria. Activity level, fatigue and
      health perception were measured by means of questionnaires. Twenty-six healthy
      persons served as control group and were matched in respect of age, gender and
      activity level. Training intervention consisted of 5x30 min sessions per week of
      bicycle exercise with individualised intensity. Compared with baseline, the MS
      training group demonstrated a significant rightward placement of the aerobic
      threshold (AT) (VO2+13%; work rate [WR])+11%), an improvement of health
      perception (vitality+46%; social interaction+36%), an increase of activity level
      (+17%) and a tendency to less fatigue. No changes were observed for the MS-NI
      group and the control groups. Maximal aerobic capacity and lung function were not
      changed by either training or nontraining in all four groups. Overall compliance
      to the training program was quite low (65%), whereas incidence of symptom
      exacerbation by physical activity has been lower than expected (6%).

PMID- 11990875
TI  - Comparison of two brief neuropsychological batteries in people with multiple
      sclerosis.
AB  - BACKGROUND: We compared two brief neuropsychological batteries devised to assess
      people with multiple sclerosis (MS) and used them to assess the relationship
      between cognitive impairment and dinical characteristics. METHODS: We
      administered either the Brief Repeatable Battery of Neuropsychological Tests
      (BRBNT) or the Screening Examination for Cognitive Impairment (SEFCI) to 213
      consecutive MS outpatients and 213 individually matched controls. RESULTS:
      Administration times were longer for BRBNT than SEFCI, for MS and controls
      (p=0.001). People with MS had lower scores in all individual tests than controls
      (p<0.001, BRBNT and SEFCI). By the criterion of poor performance on one or more
      tests, the sensitivity of BRBNT was 41.9% and that of SEFCI 31.5%. The
      corresponding figures by poor performance on two or more tests were 16.2% for
      BRBNT and 18.5% for SEFCI. The Buschke Selective Reminding and Paced Auditory
      Serial Addition were the tests best discriminating between people with MS and
      controls for BRBNT, and the Symbol Digit Modalities test for SEFCI. The only
      clinical variable independently associated with impaired performance on these
      batteries was EDSS. CONCLUSIONS: Both cognitive batteries were well accepted and
      easy to administer. Administration time for SEFCI was significantly shorter than
      for BRBNT; however, alternative forms for serial evaluation are available only
      for BRBNT. The BRBNT was slightly more sensitive in detecting impairment by the
      criterion of poor perfomance on one or more tests. EDSS score was the only
      clinical variable independently associated with cognitive impairment

PMID- 11990876
TI  - Workshop on primary progressive multiple sclerosis: meeting summary.

PMID- 11990877
TI  - Evaluation of myocardial functional parameters during intravenous
      cyclophosphamide pulse therapy: a case report.

PMID- 11990878
TI  - The pathology of primary progressive multiple sclerosis.
AB  - The present review will focus on the current knowledge of the pathology of
      primary progressive multiple sclerosis lesions. Multiple sclerosis (MS) is an
      inflammatory demyelinating disease with a broad clinical variability. The main
      disease courses are relapsing-remitting, secondary progressive and primary
      progressive MS. Pathological studies examining the specific underlying pathology
      of a defined clinical subtype are rare. Here, we focus on the pathological
      characteristics of the MS lesions and summarize the current findings of the
      pathology of primary progressive MS with respect to inflammation, oligodendrocyte
      myelin pathology, axon destruction and immunopathology of the lesions.

PMID- 11990879
TI  - APOE genotypes and disease severity in multiple sclerosis.
AB  - Apolipoprotein E (opoE) is involved in the transport of lipids necessary for
      membrane repair and is encoded by a gene on chromosome 19q13, a region positive
      for linkage in two multiple sclerosis (MS) genome-wide screens. The APOE epsilon4
      allele confers susceptibility to both familial and sporadic Alzheimer's disease
      (AD). Carriage of epsilon4 is associated with defective dendritic remodeling in
      AD, and with unfavorable clinical outcome in head trauma and cerebrovascular
      disease. According to the results of previous studies, APOE epsilon4 does not
      increase the risk of developing MS, but it may influence disease progression and
      ultimate disability. From a total cohort of over 900 MS patients, we compared
      APOE epsilon2-4 genotypes in, roughly, the cohort's least disabled and most
      disabled septiles. 'Benign MS' (n=124) was defined as an Expanded Disability
      Status Scale (EDSS) score of 3.0 or less, despite at least 10 years of disease
      duration, and 'severe MS' (n=140) as the attainment of an EDSS score of 6.0
      within 8 years of disease onset. We found no significant differences in genotype
      or phenotype frequencies between the benign-MS and severe-MS septiles; however,
      the risk conferred by epsilon4 rose progressively upon comparison of carriage
      rates in more narrowly defined anti-podal quantiles.

PMID- 11990880
TI  - The need for mental health promotion.
AB  - OBJECTIVE: To examine the concept and evidence for mental health promotion,
      within an understanding of mental health and mental illness and their
      determinants. METHOD: A selective review of literature and opinion in the fields
      of public health and mental health. RESULTS: Mental health and mental illness are
      often given a low priority, despite growing evidence of the burden of disease and
      costs to the economy. Improving mental health and reducing mental illness will
      improve quality of life, public health and productivity. The needs for mental
      health promotion are complementary to the needs for prevention and treatment of
      mental illness. The required activities are different. Mental health
      professionals have a necessary but not sufficient role in mental health
      promotion. CONCLUSIONS: An understanding that mental illnesses are treatable can
      encourage early entry to care, improve outcomes and lessen the stigma and
      discrimination related to mental illness. In primary health care there is some
      evidence that preventive interventions with groups at high risk of depression can
      prevent episodes of ill health. However, mental health promotion involves another
      dimension. Better understanding of the nature of mental health and mental illness
      is the key to changing the priorities, policies and practices in education, law,
      social services, housing and health critical in turn to the conditions conducive
      to mental health.

PMID- 11990881
TI  - Is dementia a mental illness?
AB  - OBJECTIVE: To examine whether dementia is a mental illness. METHOD: An analysis
      of decisions in the Supreme Court of New South Wales that dementia per se was not
      a mental illness in terms of the 1958 Mental Health Act. A brief review of the
      extrusion of other diseases from psychiatry. RESULTS: Concepts in legislation are
      based on a dichotomy between mental infirmity and mental illness that has changed
      over time. This change is the result of shifting perceptions about the basis of
      illness and disease and the causation of mental symptoms. Mental health
      legislation is aimed as much at social control of feared behaviour as protecting
      the ill/incompetent. Guardianship legislation offers a more holistic response
      that better meets the patient's needs and could be extended to supplant mental
      health legislation. CONCLUSIONS: Dementia's departure from mental illness
      reflects psychiatry's continuing marginalization within medicine on an outdated
      mind/body or illness/disease split. This underlines one of the psychiatrist's
      roles as the vehicle to 'medically' explain abnormal behaviour. This model means
      that behaviour, once explained in terms of disease as opposed to illness, can be
      moved from the direct responsibility of psychiatry into other areas of medicine.
      Paradoxically, this suggests that the future of psychiatry will be in a
      completely different direction from its current biological focus.

PMID- 11990882
TI  - Whose evidence? Lessons from the philosophy of science and the epistemology of
      medicine.
AB  - OBJECTIVE: To demonstrate the inadequacies of empiricism as a scientific
      foundation for evidence-based approaches to psychiatry. METHOD: The principles of
      empiricism are reviewed in the light of developments in the philosophy of science
      and phenomenology. Case studies are selected from the history of physical
      sciences, biological science and clinical sciences (pathology, neuroscience,
      psychosocial science and psychopathology), paying particular attention to the
      role of observation in theory construction. RESULTS: The principles of
      empiricism, particularly its view of the nature of observation as the basis of
      evidence do not reflect the historical reality of scientific theorizing and
      practice. Science has constructed alternative models of its own activity that do
      justice to the complexities of its subject matter, including the world of human
      experience and mental illness. CONCLUSIONS: A failure to recognize both the
      limitations of empiricism in science and the conceptual richness of alternative
      formulations that accord more closely with the complexity of psychiatry's domain
      will result in a naive model of science and inadequate understanding of the
      limitations of 'evidence' that guide the training, clinical practice and research
      in our profession. The consequences will be the intellectual, clinical and
      ethical impoverishment of psychiatry.

PMID- 11990883
TI  - Does case management work? The evidence and the abuse of evidence-based medicine.
AB  - OBJECTIVES: This study reviews typologies of psychiatric case management and then
      discusses the efficacy, effectiveness and cost effectiveness of psychiatric case
      management, with particular focus on evidence from Australia and the UK.
      Subsequently, it aims to examine the way such evidence has been interpreted in
      the context of UK psychiatric research and services. Finally it examines the ways
      in which, by the selective reviewing or editorializing of evidence, case
      management has been brought into disrepute in the UK. METHOD: This study reviews
      literature of the recent evidence for case management, and asks three questions
      of case management: has it been shown to be efficacious in controlled research,
      is it effective in applied settings, and is it cost effective? An examination is
      then made of the concurrent representations of the UK evidence in both the
      academic literature and the media. RESULTS: There is strong evidence for the
      efficacy effectiveness and cost-effectiveness of case management in psychiatry,
      the closer it conforms to active and assertive community treatment models. It
      appears, however, that studies and evidence-based reviews of case management have
      possibly been misused and misrepresented in a highly charged atmosphere of
      professional media debate. The potential for this abuse is not limited to
      psychiatry and remains a challenge for all evidence-based practice. CONCLUSION:
      On the evidence, assertive community treatment case management is one of the most
      effective interventions in psychiatry today. Despite improving the evidence base
      for practice (e.g. as has occurred for case-management in psychiatry), evidence
      based medicine (EBM) is still susceptible to compromise and misrepresentation,
      due to unexamined or undeclared bias. Unless this potential for abuse is
      recognized and checked, EBM in psychiatry is in danger of being discredited at
      the hand of some of its own proponents. There is a need for more rigorous pursuit
      of evidence-based psychiatry, including more systematic declaration of bias in
      all research, whether quantitative or qualitative in design.

PMID- 11990885
TI  - The role of early warning symptoms in the detection and prevention of relapse in
      schizophrenia.
AB  - OBJECTIVE: The capacity of most clinical programs to detect early signs of
      relapse in schizophrenia and to implement strategies to prevent clinical
      progression remains unevaluated. The aim of this paper is to review the
      literature on the detection of relapse in schizophrenia and to draw conclusions
      that may be of use in the implementation of clinical programs. METHOD: The
      relevant literature identified by standard search methods is explored and
      analysed. RESULTS: Few studies have the capacity to directly address the question
      as to whether it is possible to predict relapse with a high degree of predictive
      power. Recently, the implementation of a multifactorial approach to relapse
      prediction appears to have offered substantial benefits. CONCLUSIONS: The
      prediction of episodes of psychotic relapse is a realistic goal. Evidence
      indicates that interventions based upon programs of early detection can reduce
      rates of illness relapse. Prediction of relapse is most successful when
      implemented in a multifactorial way that involves specific and non-specific
      symptoms, structured ratings, clinical judgement, families, patients and
      clinicians.

PMID- 11990884
TI  - Suicidal behaviour in people with HIV/AIDS: a review.
AB  - OBJECTIVE: To review the existing literature on suicidal behaviour in people with
      HIV/AIDS infection. METHOD: A search on the Index Medicus/MEDLINE database was
      performed, for articles that investigated and/or reviewed suicidal behaviour in
      people with HIV at any stage of the illness. Only articles written in English
      were used in this review. RESULTS: Most studies have been done on
      homosexual/bisexual groups, with little data available for heterosexual
      populations or women. Studies show an increased rate of suicidal ideation,
      suicide attempts and completed suicide in individuals with HIV/AIDS. Of note,
      there is a high prevalence of psychiatric illness and substance abuse in those
      with suicidal behaviour. CONCLUSIONS: The increased rate of suicidal behaviour in
      HIV-infected persons is consistent with findings in other medically ill groups
      with chronic, life-threatening disorders. However, assessment of any possible
      direct effect of HIV/AIDS on suicidal behaviour is confounded by methodological
      limitations of many of the studies. More longitudinal studies encompassing other
      affected groups including heterosexual populations and women are needed to
      elucidate the relationship between suicidal behaviour and HIV/AIDS.

PMID- 11990886
TI  - Thr ageing brain: a symposium. An introduction.

PMID- 11990887
TI  - What cognitive changes can be expected with normal ageing?
AB  - BACKGROUND: This paper briefly summarizes recent evidence on the nature of
      cognitive decline, the variability in individual responses to ageing, and risk
      factors known to affect the rate of cognitive decline. METHOD: Data from the
      Canberra Longitudinal Study were used to examine the course and diversity of
      cognitive decline. The sample consisted of 887 participants aged 70-93 years, who
      were examined in 1991 and followed up in 1994 and 1998. Data summarizing
      significant risk factors for cognitive decline were based on a review of 34
      studies that examined the following predictors: education, the APOE epsilon4
      allele, health, activity and blood pressure. RESULTS: Using data from
      participants living in the community, there is evidence that cognitive speed and
      memory performance decline with age, but that crystallized abilities remain
      largely intact in those who survive for long-term follow-up. Variability in test
      scores for memory and speed increases with age. There is evidence that poor
      health, fewer years of education, lower activity, the presence of the APOE
      epsilon4 allele, and blood pressure predict faster cognitive decline.
      CONCLUSIONS: The diversity in cognitive ageing suggests that more than one
      process may be operating to produce the observed cognitive outcomes. Education,
      good health, absence of the APOE epsilon4 allele, and activity may be protective
      of cognitive decline. Preventative strategies for sustaining high intellectual
      performance in later life may therefore be possible. These findings also speak to
      the need to extend analysis beyond examining mean changes in cognitive
      performance to an analysis based on individual differences in change.

PMID- 11990888
TI  - History of depression as a risk factor for dementia: an updated review.
AB  - OBJECTIVE: This review updates an earlier meta-analysis of the data on history of
      depression as a risk factor for dementia. It also considers the available
      evidence on the hypotheses proposed to explain the association between history of
      depression and dementia. METHOD: A meta-analysis was carried out on results from
      seven case-control and six prospective studies. A qualitative review was carried
      out on the evidence related to the hypotheses to explain the association.
      RESULTS: The meta-analysis found evidence to support an association from both
      case-control studies (estimated relative risk 2.01; 95% CI 1.16-3.50) and
      prospective studies (estimated relative risk 1.87; 95% CI 1.09-3.20). However,
      the evidence did not clearly support any one hypothesis explaining the
      association. The most likely contenders are: (i) depression can be an early
      prodrome of dementia, (ii) depression brings forward the clinical manifestation
      of dementing diseases, and (iii) depression leads to damage to the hippocampus
      through a glucocorticoid cascade. CONCLUSIONS: The possibility that history of
      depression is a risk factor for dementia needs to be taken seriously and
      explanations of the association need to be further researched.

PMID- 11990889
TI  - Is depression more prevalent in old age?
AB  - OBJECTIVE: To examine the prevalence of depression in old age and to review cross
      age studies that reported age-related differences in prevalence. METHOD: Reports
      of studies that included data on the prevalence of depression in old age were
      reviewed, and conclusions from review articles were considered. RESULTS: Findings
      have been inconsistent, but majority opinion holds that depression (especially
      'subsyndromal') is common in old age. There may be two peaks in the prevalence
      rate of major depression, one in late old age and the other in middle age or
      earlier. CONCLUSIONS: The allocation of health care resources should not be
      determined by survey findings concerning the prevalence of major depression and
      dysthymia.

PMID- 11990890
TI  - Brain ageing in the new millennium.
AB  - OBJECTIVE: This paper examines the current literature pertaining to brain ageing.
      The objective of this review is to provide an overview of the effects of ageing
      on brain structure and function and to examine possible mediators of these
      changes. METHODS: A MEDLINE search was conducted for each area of interest. A
      selective review was undertaken of relevant articles. RESULTS: Although
      fundamental changes in fluid intellectual abilities occur with age, global
      cognitive decline is not a hallmark of the ageing process. Decline in fluid
      intellectual ability is paralleled by regionally specific age related changes
      apparent from both structural and functional neuroimaging studies. The
      histopathological mediators of these changes do not appear to be reduction in
      neuronal number, which, with the exception of selected hippocampal regions,
      remain relatively stable across age. At the molecular level, several mechanisms
      of age related change have been postulated. Such theoretical models await
      refinement and may eventually provide a basis for therapy designed to reduce
      effects of the ageing process. The role of possible protective factors such as
      'brain reserve', neuroprotective agents and hormonal factors in modifying
      individual vulnerability to the ageing process has been the focus of a limited
      number of studies. CONCLUSION: Our understanding of the functional and structural
      changes associated with both healthy and pathological ageing is rapidly gaining
      in sophistication and complexity. An awareness of the fundamental biological
      substrates underpinning the ageing process will allow improved insights into
      vulnerability to neuropsychiatric disease associated with advancing age.

PMID- 11990891
TI  - The mental health of young people in Australia: key findings from the child and
      adolescent component of the national survey of mental health and well-being.
AB  - OBJECTIVE: To identify the prevalence of three mental disorders (Depressive
      Disorder, Conduct Disorder and Attention-Deficit/Hyperactivity Disorder), the
      prevalence of mental health problems, the health-related quality of life of those
      with problems, and patterns of service utilisation of those with and without
      mental health problems, among 4-17-year-olds in Australia. To identify rates of
      health-risk behaviours among adolescents with mental health problems. METHOD: The
      mental disorders were assessed using the parent-version of the Diagnostic
      Interview Schedule for Children Version IV. Parents completed the Child Behaviour
      Checklist to identify mental health problems and standard questionnaires to
      assess health-related quality of life and service use. The Youth Risk Behaviour
      Questionnaire completed by adolescents was employed to identify health-risk
      behaviours. RESULTS: Fourteen percent of children and adolescents were identified
      as having mental health problems. Many of those with mental health problems had
      problems in other areas of their lives and were at increased risk for suicidal
      behaviour. Only 25% of those with mental health problems had attended a
      professional service during the six months prior to the survey. CONCLUSION: Child
      and adolescent mental health problems are an important public health problem in
      Australia. The appropriate balance between funding provided for clinical
      interventions focusing on individual children and families and funding for
      interventions that focus on populations, requires careful study. The latter are
      an essential component of any strategy to reduce mental health problems as the
      high prevalence of problems makes it unlikely that individual care will ever be
      available for all those needing help. Clinical and population health
      interventions must take into account the comorbid problems experienced by
      children with mental disorders.

PMID- 11990892
TI  - Association between allergy and anxiety disorders in youth.
AB  - OBJECTIVE: Studies have documented associations between anxiety disorders and
      allergy in adults, but these associations have not been studied extensively in
      children. The objective of this study is to examine the associations between
      allergy and six anxiety disorders (AD) in youth. METHOD: This is a data analysis
      of two epidemiologic-services studies: (i) alternative service use patterns of
      youth with serious emotional disturbance (n = 936), and (ii) methods for the
      epidemiology of child and adolescent mental disorders (n = 1285). Child
      psychiatric diagnoses were measured by the diagnostic interview schedule for
      children. Allergy was assessed by the service utilization and risk factors
      interview. RESULTS: Among ADs, the strongest association found was between
      allergy and panic disorder (adjusted odds ratio 5.0; p < or = 0.001).
      Associations of allergy and the other ADs do not seem to be clinically
      significant. CONCLUSIONS: Findings suggest that in some patients panic disorder
      may be associated with hypersensitivity of immune system. Panic disorder should
      be considered in anxious children reporting allergy when no organic cause of
      allergy is found, and likewise allergy should considered in children with panic
      disorder.

PMID- 11990893
TI  - Characteristics of adolescents with school refusal.
AB  - OBJECTIVE: To describe the characteristics of young people presenting with school
      refusal to a child and adolescent psychiatric unit and examine differences
      between those admitted for inpatient treatment and the rest. METHOD: One hundred
      and ninety-two adolescents who had been assessed or treated for school refusal
      between 1994 and 1998 at the Rivendell Unit, Sydney, Australia were identified.
      An instrument was developed and used to gather data from files. Diagnoses were
      made by the consensus of two of the investigators using DSM IV criteria from all
      sources of information. RESULTS: The commencement of school refusal generally
      occurred in the first 2 years of high school. School refusers had a high
      prevalence not only of anxiety, but also of mood and disruptive behaviour
      disorders. A family history of psychiatric illness was present in over half the
      sample. There were no differences between those subsequently admitted as
      inpatients and the rest in terms of symptom scores, family composition, family
      conflict, family separation or history of abuse. Those admitted for inpatient
      treatment were more likely to have a diagnosis of mood disorders and comorbid
      diagnoses and to have a maternal history of psychiatric illness. CONCLUSIONS:
      School refusal in adolescence can be a symptom of a variety of disorders,
      particularly anxiety and mood disorder. Treatment programs need to be geared to
      the range of diagnoses which occur in this patient group and to the various
      circumstances associated with the onset of the problem.

PMID- 11990894
TI  - The identification and treatment of depression by general practitioners.
AB  - OBJECTIVE: To assess the level of recognition and knowledge about treatment of
      depression by General Practitioners (GPs). METHOD: Analysis of questionnaires
      completed by participants commencing a series of workshops aimed at improving
      their knowledge of the diagnosis and treatment of depression. Of the 3289 GPs
      involved in the program 2500 (76% respondent rate) completed the questionnaires
      in a group situation. There was no difference between respondents and
      nonrespondents in terms of age, gender and year of graduation. RESULTS: The
      majority of GPs believe they have a satisfactory competence in the recognition
      and treatment of depression, although a sizeable minority based their diagnosis
      predominantly on somatic symptoms. The GPs felt confident about their knowledge
      and skills in counselling and the use of antidepressant medication, but not in
      dealing with children and suicidal or pregnant patients. The most common symptoms
      used to identify 'depression' were sleep disorders and only 54% listed depressed
      mood as a symptom on which the diagnosis is based. Only 28% reported sufficient
      symptoms to meet criteria for DSM-IV major depressive disorder, which supports
      views that these criteria are inappropriate for general practice. Fifty-seven
      percent of doctors used medicine together with nonpharmacological treatment in
      the majority of patients, and medications doses were almost all within the range
      recommended in the product information. CONCLUSIONS: There is a need to improve
      GPs knowledge in diagnosing depression, in child psychiatry and in dealing with
      pregnant and suicidal patients.

PMID- 11990895
TI  - Lithium toxicity: an iatrogenic problem in susceptible individuals.
AB  - OBJECTIVE: Lithium toxicity, manifesting primarily as neurotoxicity, is a
      significant health problem and is primarily iatrogenic in nature. Despite 50
      years of medical experience with lithium, factors contributing to the development
      of severe neurotoxicity remain poorly documented. We hypothesized that severe
      neurotoxicity represents the most clinically significant manifestation of lithium
      toxicity. We proposed that this occurs primarily in the context of chronic
      therapeutic administration ('chronic poisoning'), rather than in the context of
      an overdose. Furthermore we hypothesized that patients who developed chronic
      poisoning did so in the presence of identifiable factors which predictably impair
      lithium clearance. METHOD: A retrospective analysis of 97 cases of lithium
      poisoning, treated at a regional centre over a 13-year period was performed.
      Demographic data and factors considered likely to relate to the risk of
      developing lithium toxicity were recorded. Patients were classified according to
      mode of poisoning (acute, acute on chronic, or chronic) and according to severity
      of neurotoxicity (nil, mild, moderate, severe). The risk of developing severe
      neurotoxicity as a result of each mode of poisoning was assessed. The association
      between various risk factors and the development of chronic poisoning was
      assessed using a logistic regression model. RESULTS: Twenty-eight cases were
      rated as suffering severe neurotoxicity; in 26 this developed in the context of
      chronic poisoning and in two in the context of acute on chronic poisoning. All
      patients who developed severe neurotoxicity had at least one putative risk factor
      present, regardless of mode of poisoning. Length of stay was significantly longer
      for cases with severe neurotoxicity compared to those without severe
      neurotoxicity (12 vs. 2 days, P < 0.001). Peak serum lithium concentrations were
      significantly higher in cases with severe neurotoxicity compared to those without
      (2.3 vs. 1.6 mmol/L, P = 0.02). Patients presenting with chronic poisoning had a
      substantially higher risk of severe neurotoxicity than those presenting after an
      overdose of lithium (Odds Ratio [OR] 136, 95% CI 23-1300). A logistic regression
      model showed three factors contributed independently to the risk of chronic
      poisoning. These were: nephrogenic diabetes insipidus (adjusted OR 26.96, 95% CI
      2.89-251.94), age over 50 years (adjusted OR 6.20, 95% CI 1.36-28.32) and thyroid
      dysfunction (adjusted OR 9.30, 95% CI 1.36-63.66). A fourth factor, baseline
      endogenous creatinine clearance below normal limits, was significant at the P =
      0.05 level (adjusted OR 6.49, 95% CI 0.98-43.01). Hyperparathyroidism was noted
      in three cases of chronic poisoning suffering severe neurotoxicity. CONCLUSION:
      Severe lithium neurotoxicity occurs almost exclusively in the context of chronic
      therapeutic administration of lithium, and rarely results from acute ingestion of
      lithium, even in patients currently taking lithium. As such it is an iatrogenic
      illness, occurring in patients who have identifiable clinical risk factors:
      nephrogenic diabetes insipidus, older age, abnormal thyroid function and impaired
      renal function. Although administration of drugs which impair lithium clearance
      appeared to contribute minimally to chronic lithium poisoning in the absence of
      other factors, these drugs may well 'uncover' the predisposing risk factors and
      certainly should not be considered safe to use as a consequence of this study.
      The serious morbidity suffered by lithium toxic patients, and the cost to society
      due to long hospital stays, might be reduced by careful prescribing, vigilant
      monitoring and awareness of these factors, as they develop in otherwise stable
      patients. Review of existing therapeutic guidelines may be warranted.

PMID- 11990896
TI  - Types of patients in a psychiatric intensive care unit.
AB  - OBJECTIVE: This paper reports the findings of a descriptive study of a patient
      population over a three-month period on an eight bed psychiatric intensive care
      unit (PICU) in Western Australia. The report provides a quantitative insight into
      the profile of patients in PICUs. It provides information on patients' diagnoses,
      presenting signs, symptoms and/or behaviours, legal codes assigned to patients,
      treatment interventions and management. METHOD: Data were collected prospectively
      from August to October 1999. A total of 122 patients were admitted to the PICU
      during the review period. Data were entered into an Access program then exported
      to SPSS (Version 9 for Windows) for analysis and frequency distributions were
      obtained. RESULTS: The results confirmed that the majority of patients admitted
      to the PICU were assessed as a high level of risk or needed containment. This
      finding is in line with the admission criteria developed by staff working in the
      PICU. It also supports the view that staff working in these units require
      expertise and confidence to communicate with and manage potentially aggressive
      and highly aroused patients. CONCLUSION: This study demonstrates the importance
      of ongoing evaluations of patient populations in promoting best practice
      initiatives in psychiatric care.

PMID- 11990897
TI  - Defining disability in psychosis: performance of the diagnostic interview for
      psychosis-disability module (DIP-DIS) in the Australian National Survey of
      Psychotic Disorders.
AB  - OBJECTIVE: We aimed to use data from the Australian Survey of Mental Health and
      Wellbeing to examine the psychometric properties of the Diagnostic Interview for
      Psychosis-Disability Module (DIP-DIS). The DIP-DIS is a semi-structured
      questionnaire specially designed to assess disability associated with psychotic
      disorders. METHOD: The psychometric properties of the instrument were determined
      by examining its inter-rater reliability, internal structure, as well as its
      criterion and discriminant validities. RESULTS: Analysis shows: (1) that it can
      be rated reliably by trained interviewers, (2) that the items are complementary
      but tap a number of different domains, (3) that four factors account for over 66%
      of the variance, and (4) that it is sensitive to differing clinical populations
      with expected differences in level of disability. Ratings on the DIP-DIS bore
      significant relationships with a criterion measure of quality of life.
      CONCLUSIONS: The DIP-DIS has encouraging psychometric properties for cross
      sectional assessment of disability and may be useful in future studies of
      disablement associated with psychosis. Future work should examine its sensitivity
      to change.

PMID- 11990898
TI  - Lithium toxicity presenting as non-convulsive status epilepticus (NCSE).

PMID- 11990899
TI  - Bicultural training and Maori mental health services.

PMID- 11990900
TI  - Successful treatment of steroid-induced depression with low dosage of
      fluvoxamine.

PMID- 11990901
TI  - Olanzapine and pregnancy.

PMID- 11990902
TI  - Trauma evidence and litigation.

PMID- 11990903
TI  - The prolongation of QTc-interval by thioridazine.

PMID- 11990904
TI  - Comparing CIDI and clinical assessment.

PMID- 11990905
TI  - Depletion of neurohypophyseal content of vasopressin in septic shock.
AB  - OBJECTIVES: To assess the mechanisms underlying the inappropriately low plasma
      vasopressin levels reported in septic shock. DESIGN: Prospective case series.
      SETTING: A 26-bed general medical intensive care unit at a university hospital.
      PATIENTS: Septic shock patients. MEASUREMENTS AND MAIN RESULTS: In three
      consecutive patients with septic shock, plasma vasopressin levels, circulating
      vasopressinase activity, baroreflex sensitivity, and neurohypophyseal vasopressin
      content were assessed. Plasma vasopressin concentration was unexpectedly within
      normal range in two patients (1.6 pg/mL and 1.8 pg/mL) and increased in one (16
      pg/mL). In all cases, vasopressinase activity was undetectable, baroreflex
      sensitivity was decreased, and the high signal intensity of the posterior lobe of
      the pituitary gland on T1-weighted magnetic resonance images was absent. Magnetic
      resonance imaging and plasma vasopressin levels normalized after recovery from
      shock in the patient who survived. CONCLUSION: These data suggest that in septic
      shock, inappropriately low plasma levels of vasopressin are at least partly
      related to a depletion of vasopressin stores in the neurohypophysis.

PMID- 11990906
TI  - Intensive care unit admission has minimal impact on long-term mortality.
AB  - OBJECTIVE: To measure the association between intensive care unit (ICU) admission
      and both hospital and long-term mortality, separate from the effect of hospital
      admission alone. DESIGN: Retrospective cohort study. SETTING: All hospitals in
      British Columbia, Canada, during 3 fiscal years, 1994 to 1996. PATIENTS: A total
      of 27,103 patients admitted to ICU and 41,308 (5% random sample) patients
      admitted to hospital but not to ICU. INTERVENTION: None. MEASUREMENTS AND MAIN
      RESULTS: Although ICU admission was an important factor associated with hospital
      mortality (odds ratio: 9.12; 95% confidence interval: 8.34-9.96), the association
      between ICU admission and mortality after discharge was relatively minimal
      (hazard ratio: 1.21; 95% confidence interval: 1.17-1.27) and was completely
      overshadowed by the effect of age, gender, and diagnosis. CONCLUSIONS: After
      controlling for the effect of hospital admission, admission to ICU has minimal
      independent effect on mortality after discharge.

PMID- 11990907
TI  - L-arginine supplementation in hyperdynamic endotoxemic pigs: effect on nitric
      oxide synthesis by the different organs.
AB  - OBJECTIVES: Under septic conditions, the protective role of nitric oxide in the
      organs may become compromised at a time of increased demand as a result of
      decreased availability of L-arginine. It remains unknown whether supplementation
      with L-arginine, as a substrate, can modulate organ nitric oxide production.
      DESIGN: Controlled study with laboratory animals. SETTING: University research
      laboratory. SUBJECTS: Female crossbred pigs. INTERVENTION: Pigs were challenged
      with Escherichia coli endotoxin (intravenously) and received intravenous fluid
      resuscitation for 24 hrs to reproduce a model of long-lasting hyperdynamic
      endotoxemia. Pigs were infused with either L-arginine or L-alanine intravenously
      during endotoxin and via the intragastric route after cessation of endotoxin
      infusion. The effects of L-arginine supplementation on nitric oxide synthesis and
      the relationships with arginine metabolism were determined with a stable isotope
      infusion protocol. Also, organ nitrite plus nitrate fluxes were measured.
      Implantation of multiple catheters enabled in vivo measurements across the
      hindquarter muscle, the portal-drained viscera, the liver, and the kidneys.
      MEASUREMENTS AND RESULTS: The isotope conversion method showed that L-arginine
      intervention significantly increased nitric oxide production by the portal
      drained viscera, liver, and kidneys, resulting in elevated whole-body nitric
      oxide synthesis under endotoxemic and postendotoxemic conditions. Organ nitrite
      plus nitrate fluxes only tended to increase because of high variance among data.
      CONCLUSIONS: In this endotoxemia model, supplemental use of L-arginine favored
      nitric oxide synthesis in various organs.

PMID- 11990908
TI  - Bioelectrical impedance analysis for assessment of severity of illness in
      pediatric patients after heart surgery.
AB  - OBJECTIVE: To investigate whether perioperative changes in bioelectrical
      impedance reflect the severity of illness in pediatric patients after heart
      surgery. DESIGN: Prospective, controlled study. SETTING: University-affiliated
      children's hospital. PATIENTS: A total of 107 patients admitted to a pediatric
      intensive care unit after congenital heart surgery. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Single frequency (50 kHz) bioelectrical impedance
      was measured in the lower extremities before surgery and immediately, 16 hrs, and
      40 hrs after admission (D0, D1, D2) to the pediatric intensive care unit.
      Postoperative changes in bioelectrical impedance were assessed by calculating
      values relative to the preoperative data (bioelectrical impedance ratio). These
      bioelectrical impedance ratios at D0 in both the nonsurviving and surviving
      patients were 0.84 +/- 0.06 and 0.85 +/- 0.01 (mean +/- SE), respectively,
      indicating that the initial decrease caused by surgical stress itself was not
      directly related to the prognosis. The bioelectrical impedance ratio showed an
      increase toward preoperative values in surviving patients (0.94 +/- 0.02) at D1,
      and they showed a sustained decrease (0.70 +/- 0.06) in nonsurviving patients.
      Patients with a bioelectrical impedance ratio at D1 of < 0.8 showed a higher
      mortality (25%) compared with those patients with a day-1 bioelectrical impedance
      ratio of > or = 1.0 (0%). The duration of the stay in the pediatric intensive
      care unit, mechanical ventilation, and inotropic support were all significantly
      longer in the patients with the lower bioelectrical impedance ratio. CONCLUSIONS:
      Measurement of the relative changes in postoperative bioelectrical impedance,
      which reflects perioperative alterations in body composition, provides a
      quantitative estimation of the critical illness in pediatric patients after heart
      surgery.

PMID- 11990909
TI  - Type III protein secretion is associated with poor clinical outcomes in patients
      with ventilator-associated pneumonia caused by Pseudomonas aeruginosa.
AB  - OBJECTIVE: Pseudomonas aeruginosa is a frequent cause of ventilator-associated
      pneumonia. Recent evidence suggests that production of type III secretion
      proteins is correlated with increased pathogenicity in both cellular and animal
      models of infection. The objective of this study was to determine whether this
      system contributes to disease severity in humans with ventilator-associated
      pneumonia. DESIGN: Retrospective pilot cohort study. SETTING: University
      hospital. PATIENTS: Thirty-five mechanically ventilated patients with
      bronchoscopically confirmed ventilator-associated pneumonia caused by P.
      aeruginosa. MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia was
      categorized as severe (patients died or had a recurrence of their pneumonia
      despite appropriate antibiotic therapy) or mild (patients uneventfully recovered
      from their pneumonia). The type III secretion genotypes and phenotypes of
      isolates cultured from the patients with ventilator-associated pneumonia were
      determined. Whereas every examined isolate harbored type III secretion genes,
      only 27 (77%) were capable of secreting detectable amounts of type III proteins
      in vitro. Twenty-two (81%) of the patients infected with these 27 isolates had
      severe disease. Of the eight isolates that did not secrete type III proteins,
      only three (38%) were cultured from patients with severe disease. Thus, infection
      with a type-III-secreting isolate correlated with severe disease (p < .05). In
      vitro assays indicated that ExoU, the type III effector protein most closely
      linked to mortality in animal models, was secreted in detectable amounts in vitro
      by 10 (29%) of the 35 examined isolates. Nine (90%) of these 10 isolates were
      cultured from patients with severe disease (p < .05 when compared with the
      nonsecreting isolates). In contrast, ExoS was secreted by 16 (46%) of the 35
      examined isolates. Twelve (75%) of these 16 isolates were cultured from patients
      with severe disease (p = .14 when compared with the nonsecreting isolates).
      CONCLUSIONS: In patients with ventilator-associated pneumonia, type-III-secreting
      isolates were associated with worse clinical outcomes, suggesting that this
      secretion system plays an important role in human disease. Our findings support
      the hypothesis that antibodies targeted against these proteins may be useful as
      adjunctive therapy in intubated patients with P. aeruginosa colonization or
      infection.

PMID- 11990910
TI  - Diagnosis and follow-up of infections in intensive care patients: value of C
      reactive protein compared with other clinical and biological variables.
AB  - OBJECTIVE: To evaluate diagnostic and prognostic values of C-reactive protein
      (CRP) dosage in critically ill patients. DESIGN: Prospective, observational
      study. SETTING: Medical intensive care unit (ICU) in a university hospital.
      PATIENTS: A consecutive series of 74 patients admitted to the ICU. INTERVENTION:
      CRP measurements at admission and every 4 days thereafter. MEASUREMENTS AND MAIN
      RESULTS: At admission, 28 patients (38%) had microbiologically proven infections.
      Compared with uninfected patients, their mean +/- SD CRP level was 191 +/- 123
      vs. 83 +/- 91 mg/L (p < .0001), respectively, white blood cell count was 15.3 +/-
      7.5 vs. 11.4 +/- 5.3 G/L (p = .01), and the systemic inflammatory response
      syndrome (SIRS) was present for 96% vs. 67% (p = .008). No threshold value could
      be identified to discriminate between these two populations. Multivariate
      analysis retained CRP and SIRS as the only variables independently associated
      with the presence of an infection. The combination of CRP > or = 50 mg/L with
      SIRS was identified as the best model to diagnose infection at admission. This
      multivariate model performed better than temperature, CRP alone, and white blood
      cell count. Among the 28 infected patients, 10 recovered; CRP values decreased
      significantly in this population as compared with patients with persistent
      infection (-130 +/- 110 vs. 12 +/- 97 mg/L, respectively; p = .004). A CRP
      decrease > or = 50 mg/L between admission and day 4 was the best cutoff value to
      diagnose recovery (sensitivity 89%, specificity 79%). CONCLUSION: CRP in
      combination with SIRS was useful to diagnose infection in ICU patients; a CRP
      decrease > or = 50 mg/L between admission and day 4 was the best predictor of
      recovery.

PMID- 11990911
TI  - Impaired circadian rhythm of melatonin secretion in sedated critically ill
      patients with severe sepsis.
AB  - OBJECTIVE: Melatonin is involved in the regulation of the sleep-wake cycle and
      exhibits multiple interactions with the neuroendocrine and the immune system.
      Melatonin secretion in healthy individuals follows a stable circadian rhythm.
      Critical illness, continuous administration of drugs, and loss of external
      zeitgeber might impair the circadian rhythm of melatonin secretion in the
      intensive care unit (ICU), thereby compromising the physiologic stress-induced
      immune response. DESIGN: Prospective, controlled clinical study. SETTING: Medical
      intensive care unit in a university hospital. PATIENTS: Seventeen septic, sedated
      ICU patients (group A); 7 nonseptic ICU patients (group B); and 21 control
      patients (group C) were studied. MEASUREMENTS AND MAIN RESULTS: 6
      Sulfatoxymelatonin (aMT6s) was determined from urine samples taken at 4-hr
      intervals over a total period of 24 hrs. aMT6s was measured by enzyme-linked
      immunosorbent assay. Circadian mesors, phase amplitudes, and timing of the
      acrophase were assessed by cosinor analysis. Differences between groups were
      calculated by contingency data analysis and by analysis of variance. Circadian
      mesors of urinary aMT6s were 3904 +/- 1597, 2622 +/- 927, and 3183 +/- 1514 ng/4
      hrs in groups A, B, and C, respectively (p = NS). aMT6s exhibited significant
      circadian periodicity in only 1/17 (6%) patients of group A but in 6/7 (86%)
      patients of group B and in 18/23 (78%) patients of group C (group A vs. groups B
      and C: p = .0001) Phase amplitudes were markedly lower in group A (1071 +/- 1005
      ng/4 hrs) compared with group B (2284 +/- 581 ng/4 hrs, p = .009) and C (2838 +/-
      2255 ng/4 hrs, p = .006). The acrophase was significantly delayed in patients of
      group A (10:35 am +/- 255 mins) compared with group B (05:43 am +/- 114 mins, p =
      .01) and group C (4:20 am +/- 107 mins, p < .0001). In sepsis survivors, aMT6s
      excretion profiles tended to normalize, but still lacked a significant circadian
      rhythm at ICU discharge. CONCLUSION: The present study revealed striking
      abnormalities in urinary aMT6s excretion in septic ICU patients. In contrast,
      circadian rhythm was preserved in nonseptic ICU patients, indicating that
      impaired circadian melatonin secretion in septic patients is mainly related to
      the presence of severe sepsis and/or concomitant medication. Further
      investigations are required to examine the underlying pathophysiologic mechanism
      and the clinical implications of this finding.

PMID- 11990912
TI  - Significance of Candida recovered from intraoperative specimens in patients with
      intra-abdominal perforations.
AB  - OBJECTIVE: Determine the significance of recovering yeasts from intraoperative
      specimens from the abdominal cavity and to evaluate the effect of a single
      intraoperative dose of fluconazole on clinical outcome in patients with intra
      abdominal perforations. DESIGN: Prospective, randomized, double-blind study.
      SETTING: Multicenter study from 13 hospitals in Norway. PATIENTS: One hundred
      nine patients with intra-abdominal perforations. INTERVENTIONS: Patients were
      randomized to receive either a single 400-mg fluconazole dose or placebo during
      the operation. MEASUREMENTS AND MAIN RESULTS: An intra-abdominal specimen for
      microbiological culture was obtained at the time of the operation. The primary
      response variable in the study was death. Secondary response variables were three
      parameters indicating a complicated postoperative period: mechanical ventilation
      for > or = 5 days, intensive care treatment for > or = 10 days, and use of a
      central venous catheter for > or = 10 days. Yeasts were recovered from a
      intraoperative intra-abdominal specimen from only 1 (3.5%) of 28 patients with
      perforated appendicitis and from 32 (39.5%) of 81 nonappendicitis patients.
      Excluding the appendicitis patients, the yeast recovery rate was high both for
      patients hospitalized at the time of the perforation (45%) and for
      nonhospitalized patients (32%). The overall mortality was 11% (12 patients).
      Single-dose intraoperative fluconazole prophylaxis did not reach a statistically
      significant effect on mortality (4 of 53 patients in the fluconazole group and 8
      of 56 patients in the placebo group died [p = .059]). The only two explanatory
      variables significantly related to death were a intraoperative finding of yeast
      from an intra-abdominal specimen and the occurrence of a spontaneous perforation
      in a patient already hospitalized for nonsurgical cancer treatment. Detection of
      yeast was also a significant explanatory variable for a prolonged period of
      mechanical ventilation, intensive care treatment, and prolonged use of a central
      venous catheter. CONCLUSIONS: Single-dose intraoperative fluconazole prophylaxis
      did not have a statistically significant effect on overall mortality (odds ratio
      = 0.21; 95% confidence interval, 0.04-1.06; p = .059) in patients with intra
      abdominal perforation. The recovery rate of yeast from intraoperative specimens
      from the abdominal cavity was high (>30%) and was associated with death and a
      complicated postoperative course.

PMID- 11990913
TI  - Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized,
      placebo-controlled, phase II clinical trial.
AB  - OBJECTIVE: To establish the safety of intravenous dexanabinol in severe head
      injury. DESIGN: Prospective, randomized, double-blind, placebo- (vehicle)
      controlled, multicenter, escalating dose study of a single administration of drug
      (48 or 150 mg) or vehicle (1 or 3 mL). SETTING: All Israeli neurosurgical
      intensive care units (a total of six units). PATIENTS: Sixty-seven patients, aged
      16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment.
      MEASUREMENTS AND MAIN RESULTS: Intracranial pressure, cerebral perfusion
      pressure, blood pressure, and heart rate were measured continuously in the
      intensive care unit. Adverse medical events were recorded and clinical outcome
      was assessed by the Glasgow outcome scale throughout a 6-month follow-up period.
      A highly significant reduction in the percentage of time with intracranial
      pressure >25, cerebral perfusion pressure <50, and systolic blood pressure <90 mm
      Hg was observed in the drug-treated group. The nature and incidence of adverse
      medical events were similar in the two groups. The percentage of patients
      achieving good neurologic outcome on the Glasgow outcome scale was 21% and 14%
      higher in the drug-treated group at 3 and 6 months, respectively. Statistical
      analysis of these differences by a logistic model using dose, entry Glasgow coma
      scale score, and computed tomograph as covariates yielded p values for the effect
      of treatment of .03 and .14 at 3 and 6 months, respectively. CONCLUSIONS:
      Dexanabinol was safe and well tolerated in severe head injury. The treated
      patients achieved significantly better intracranial pressure/cerebral perfusion
      pressure control without jeopardizing blood pressure. A trend toward faster and
      better neurologic outcome was also observed.

PMID- 11990914
TI  - Noninvasive ventilation in acute respiratory failure--a meta-analysis update.
AB  - OBJECTIVE: To present a meta-analytic update on the effects of noninvasive
      ventilation (NIV) in the management of acute respiratory failure. DESIGN: Meta
      analysis of randomized controlled clinical trials in acute respiratory failure
      comparing NIV with standard medical therapy. PATIENTS: Randomized controlled
      trials of NIV in acute respiratory failure were identified by search of i)
      MEDLINE (1966-2000), ii) published abstracts from scientific meetings, and iii)
      bibliographies of relevant articles. MEASUREMENTS AND MAIN RESULTS: Of the 15
      randomized controlled trials that were identified (13 published and 2 in abstract
      form), 8 studies were on exacerbations of chronic obstructive pulmonary disease
      (COPD) and 7 on diverse disease processes in both COPD and non-COPD groups
      ("mixed-group"). Because of underlying heterogeneity of treatment effects, only
      the DerSimonian-Laird random effects estimator was used and reported. The effects
      of NIV vs. standard therapy on mortality and subsequent invasive mechanical
      ventilation (MV) was assessed as risk difference, and hospital length of stay as
      mean weighted difference (days). NIV was associated with reduction in mortality
      (8%, p = .03), reduced need for MV (19%, p = .001) and shortened hospital length
      of stay (2.74 days, p = .004). In the COPD cohort, significant reductions in
      mortality (13%, p = .001), need for MV (18%, p = .02), and hospital length of
      stay (5.66 days, p = .01) were observed in the group treated with NIV. In
      contrast, in the mixed-group, there was no demonstrable reduction in mortality
      (0%, p = .98). However, there was significant reduction in the need for MV (22%,
      p = .001). Publication bias was not evident on analysis. Treatment effect i) as
      mortality or need for mechanical ventilation was not modified by enrollment pH,
      PaCO2, nor age and ii) was not related (as log odds ratio) to underlying risk
      (control arm log odds). Cumulative meta-analysis did not demonstrate any
      substantial variation in the point estimates with the addition of the recently
      published studies. However a contraction in the confidence intervals was observed
      in the COPD subgroup. Complication rates were not significantly different in the
      standard medical therapy group and the NIV treated patients. CONCLUSION:
      Substantial reductions in mortality and the need for subsequent MV were
      associated with NIV in acute respiratory failure, especially in the COPD
      subgroup. Hospital length of stay was variably affected. Heterogeneity of
      treatment effects was observed.

PMID- 11990915
TI  - Continuous measurement of cerebral blood flow velocity using transcranial Doppler
      reveals significant moment-to-moment variability of data in healthy volunteers
      and in patients with subarachnoid hemorrhage.
AB  - OBJECTIVE: The reliability of intermittent transcranial Doppler has not been
      accepted widely because of problems with interobserver variability and lack of
      accuracy. The limitations of intermittent transcranial Doppler are thought to be
      overcome by continuous measurement systems. However, little published data exist
      on their accuracy, feasibility, and moment-to-moment variability. In this study
      we aimed to determine the time-related variability of continuous transcranial
      Doppler signal from volunteers and patients with subarachnoid hemorrhage and to
      examine the feasibility, ease of use, and quality of data generated from
      continuous transcranial Doppler for the detection of vasospasm. DESIGN:
      Prospective observational study. SETTING: Intensive care unit in a tertiary
      referral center. SUBJECTS: Ten volunteers and eight patients with aneurysmal
      subarachnoid hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The
      middle cerebral artery blood flow velocities were recorded continuously from both
      patients and volunteers. The moment-to-moment variability of continuously
      recorded data was calculated. There was a wide range of velocity measurements in
      both volunteers and patients. There was a significant moment-to-moment
      variability in both volunteers (-31% to 58%) and in patients (-38% to 78%). There
      was a greater number of observations exceeding 10% moment-to-moment variability
      in the patient group with regard to systolic and diastolic velocities compared
      with volunteers (8% vs. 2%, p < .001). There was a trend toward a longer duration
      of good quality data in volunteers compared with patients (98 +/- 0.5% vs. 96 +/-
      9%). CONCLUSIONS: Continuous measurement of cerebral blood flow velocities
      revealed a significant moment-to-moment variability in both patients and in
      volunteers, the magnitude of which was greater in the patients. The clinical
      implications of these findings are discussed.

PMID- 11990916
TI  - Relationship between premortem and postmortem diagnosis in critically ill bone
      marrow transplantation patients.
AB  - OBJECTIVES: To determine the relationship between the premortem and postmortem
      diagnosis in critically ill bone marrow transplantation patients Also, to
      evaluate the appropriateness of the reliance on clinical diagnosis for withdrawal
      of active treatment decision-making. DESIGN: Retrospective cohort study. SETTING:
      Two university-affiliated tertiary care medical surgical intensive care units.
      PATIENTS: Critically ill bone marrow transplantation patients who died in the
      intensive care unit between November 1,1994, and June 30,1999, and underwent
      postmortem examination. INTERVENTION: Review of medical records by two
      independent data extractors. Clinical diagnosis and cause of death in the
      intensive care unit were compared with the final autopsy report. MEASUREMENTS AND
      MAIN RESULTS: Premortem clinical diagnoses were classified according to the
      Goldman criteria and compared with postmortem findings. Twenty-eight autopsies
      were done. Ten of 28 (36%) patients had discrepancies uncovered on autopsy; only
      two discrepancies would have influenced patient management and none would have
      altered patient outcome. Twenty patients had their active treatment withdrawn and
      underwent postmortem examination. None of the discrepancies noted would have
      altered outcome in these patients. CONCLUSION: In the bone marrow transplantation
      population, there is significant concordance between clinical diagnosis and
      postmortem findings. Reliance on clinical diagnosis may be valid for withdrawal
      of active treatment decision-making in these patients.

PMID- 11990917
TI  - The hazard of scattered radiation in a trauma intensive care unit.
AB  - OBJECTIVE: Patients admitted to the trauma intensive care unit (TICU) often
      require bedside imaging procedures such as radiographs, fluoroscopic placement of
      enteral feeding tubes, and insertion of vena cava filters. The potential for
      scattered radiation exposure is a concern to healthcare workers. Our study's
      purpose was to measure the level of scattered ionizing radiation present in a
      TICU. DESIGN AND SETTING: This prospective study was conducted over 3 months in
      an open-design, ten-bed TICU of a Level I trauma center. INTERVENTIONS AND
      MEASUREMENTS: Fifteen dosimeters were placed in selected areas of the TICU to
      measure the amount of scattered radiation present. Standard radiation protection
      precautions were used throughout the study period. At the end of each month, data
      from the dosimeters were sent to the manufacturer for analysis. MAIN RESULTS: One
      thousand seventy-four radiologic studies were performed at the bedside during the
      study period (803 portable chest radiographs, 103 abdominal radiographs, 303
      extremity radiographs, 223 spine radiographs, and 15 fluoroscopic procedures).
      Dosimetry analysis showed <5 mrem (1/1000 roentgen equivalent in man) scattered
      radiation per month (<60 mrem/year) in each of the monitored areas. All monitored
      areas measured <2 mrem per week of scattered radiation when adjusted for
      occupancy. CONCLUSIONS: The level of scattered radiation in our TICU is less than
      the recommended allowable exposure of <100 mrem/year, indicating that radiation
      exposure is not a significant occupational hazard in our TICU, even in the
      setting of frequent use of bedside imaging studies.

PMID- 11990918
TI  - Extracorporal life support for pulmonary hemorrhage in children: a case series.
AB  - OBJECTIVE: To examine the use and outcome of extracorporeal life support in
      children with severe respiratory failure caused by pulmonary hemorrhage. DESIGN:
      Retrospective case series report. SETTING: Pediatric intensive care unit in a
      university children's hospital. PATIENTS: Eight patients <19 yrs of age who
      required extracorporeal life support for severe respiratory failure associated
      with pulmonary hemorrhage. INTERVENTIONS: Venoarterial or venovenous
      extracorporeal life support. MEASUREMENTS: Ventilatory support parameters and
      systemic PaO2/FiO2 ratio before extracorporeal life support, time on
      extracorporeal life support, number of ventilator days, number of intensive care
      unit days, number of hospital days, continued bleeding on extracorporeal life
      support, and survival. MAIN RESULTS: All patients had resolution of their
      pulmonary hemorrhage within 24 hrs. All patients survived to decannulation,
      extubation, and hospital discharge. All patients are alive, with follow-up times
      ranging from 1 to 10 yrs. CONCLUSIONS: Extracorporeal life support is not
      contraindicated in patients with severe respiratory failure with associated
      pulmonary hemorrhage and may be a life-sustaining supportive therapy.

PMID- 11990919
TI  - Acute severe asthma: differences in therapies and outcomes among pediatric
      intensive care units.
AB  - OBJECTIVE: To determine differences in therapies and outcomes among pediatric
      intensive care units for patients with acute severe asthma. DESIGN: Retrospective
      cohort study. SETTING: Eleven pediatric intensive care units participating in the
      Pediatric Intensive Care Evaluations. PATIENTS: Patients were 1528 children with
      a primary diagnosis of asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: We studied severity of illness, length of stay, and use of invasive
      interventions. The patients at the centers had similar median physiologic
      measures of illness and Pediatric Risk of Mortality III scores. The patients
      received a wide range of invasive interventions depending on institution,
      including mechanical ventilation (3% to 47%), arterial catheter placement (4% to
      46%), central venous catheter (2% to 51%), and determination of a blood gas (24%
      to 70%). At institutions where mechanical ventilation was used more commonly
      (>20%, high use), intensive care and hospital stays were longer for asthmatic
      patients regardless of mechanical ventilation requirement compared with centers
      with lower use of mechanical ventilation. The status of "high-use center" was an
      independent predictor for intensive care stay (p = .005) and hospital length of
      stay (p = .017) as well as duration of mechanical ventilation (p = .014) after
      adjustment for age, degree of hypercarbia, maximal respiratory rate, use of an
      arterial catheter, and Pediatric Risk of Mortality III scores among ventilated
      children. CONCLUSIONS: We found that use of invasive interventions including
      mechanical ventilation and vascular monitoring varied greatly by institution.
      Centers with higher use of mechanical ventilation had longer median intensive
      care stay and hospital stays. Pediatric asthma management for acute severe asthma
      may be improved by clear elucidation of the institutional practices where fewer
      invasive interventions were used to achieve better outcomes.

PMID- 11990920
TI  - Randomized comparison of nasojejunal and nasogastric feeding in critically ill
      patients.
AB  - OBJECTIVE: Critically ill patients often develop large gastric residual volumes
      during nasogastric feeding as a result of poor gastroduodenal motility.
      Nasojejunal feeding may decrease the severity of this complication. The aim of
      this study was to determine whether nasojejunal feeding improved tolerance of
      enteral nutrition by reducing gastric residual volumes. DESIGN: Randomized,
      prospective, clinical study. SETTING: Intensive care unit of a university
      affiliated hospital. PATIENTS: Seventy-three intensive care unit patients
      expected to require nutritional support for at least 3 days. INTERVENTIONS:
      Patients were randomized to receive enteral nutrition via a nasojejunal tube
      (placed endoscopically) (34 patients) or a nasogastric tube (39 patients). A
      strict protocol was followed, which included regular gastric residual volume
      measurement (in both groups), the use of predetermined criteria for intolerance,
      and an attempt at nasojejunal feeding for those nasogastrically fed patients who
      were intolerant of enteral nutrition. MEASUREMENTS AND MAIN RESULTS: Endoscopic
      placement of nasojejunal tubes was successful in 98% with no complications of
      insertion. Patients fed via a nasojejunal tube had 1) a reduced total gastric
      residual volume in both the first 24 (197 vs. 491 mL, p = .02) and 48 hrs (517
      vs. 975 mL, p = .02); 2) a reduced incidence of a single gastric residual volume
      >150 mL (32% vs. 74%, p = .001); and 3) a trend toward a reduced incidence of
      intolerance of enteral nutrition (13% vs. 31%, p = .09). Only 13% of those
      nasogastrically fed patients who were initially intolerant of enteral nutrition
      remained intolerant once fed via a nasojejunal tube, and only 1.4% of all
      patients met criteria for commencement of parenteral nutrition. CONCLUSIONS:
      Enteral nutrition delivered via a nasojejunal tube is associated with a
      significant reduction in gastric residual volume, a strong trend toward improved
      tolerance of enteral nutrition, and an extremely low requirement for parenteral
      nutrition.

PMID- 11990921
TI  - Tumor necrosis factor-alpha-stimulated polymorphonuclear leukocytes suppress
      migration and bactericidal activity of polymorphonuclear leukocytes in a
      paracrine manner.
AB  - OBJECTIVE: Polymorphonuclear leukocytes (PMN) and tumor necrosis factor-alpha
      (TNF-alpha) play prominent roles in acute respiratory distress syndrome, ischemia
      reperfusion injury, trauma, and sepsis. Whereas direct effects of TNF-alpha on
      PMN function and viability are well documented, little data are available
      addressing the ability of PMN to communicate with each other in response to
      cytokine stimulation. Therefore, the aim of this study was to determine whether
      TNF-alpha can modulate PMN function by inducing PMN to secrete products upon
      stimulation, which would affect other PMN in vitro in a manner independent of
      cell contact. METHODS: PMN were purified daily from blood obtained from a pool of
      22 healthy volunteers. Conditioned media (CM-TNF) was prepared by incubating PMN
      in Hanks' balanced salt solution plus TNF-alpha for 1-4 hrs. Freshly isolated PMN
      were resuspended in CM-TNF and analyzed for 1) phagocytosis of opsonized
      Escherichia coli, 2) oxidative metabolism as measured as an index of DCF-DA
      activation, and 3) migration to chemoattractants through Transwell inserts.
      RESULTS: CM-TNF decreased PMN phagocytotic activity by 8% to 15% and completely
      suppressed oxidative metabolism but did not modulate the expression of receptors
      associated with these functions. CM-TNF suppressed the migration of PMN to two
      biologically relevant agents, N-formyl-methionyl-leucyl-phenylalanine and
      leukotriene B4, by approximately 65%, but had no effect on PMN migration to
      interleukin-8. This suppression was observed for migration across plastic filters
      as well as extracellular matrix proteins. CONCLUSION: Our data demonstrate that
      PMN stimulated with TNF-alpha suppress the immunologic function and migration of
      other PMN independent of cell-cell contact and suggest that TNF-alpha may
      participate in a negative feedback loop by inducing a PMN-derived factor that
      counteracts its activity.

PMID- 11990922
TI  - Green skin discoloration associated with multiple organ failure.
AB  - OBJECTIVE: To report intense green hyperpigmentation related to FD & C Blue No.
      1. DESIGN: Retrospective case review. SETTING: Surgical intensive care unit.
      PATIENT: A 67-yr-old woman with unstable angina, electrocardiographic S-T segment
      elevation, and a left ventricle thrombus requiring emergent coronary
      revascularization surgery. INTERVENTIONS: Postoperative monitoring and treatment
      for multiple organ dysfunction that included small-bowel tube feeding and
      propofol sedation. MEASUREMENTS AND MAIN RESULTS: The patient developed an
      intense green skin color. CONCLUSION: Patients with multiple organ failure may be
      at risk for unusual pigmentation effects from tube feeding dyes.

PMID- 11990923
TI  - New treatment of acute hypoxemic respiratory failure: noninvasive pressure
      support ventilation delivered by helmet--a pilot controlled trial.
AB  - OBJECTIVE: To assess the efficacy of noninvasive pressure support ventilation
      (NPSV) using a new special helmet as first-line intervention to treat patients
      with hypoxemic acute respiratory failure (ARF), in comparison to NPSV using
      standard facial mask. DESIGN AND SETTING: Prospective clinical pilot
      investigation with matched control group in three intensive care units of
      university hospitals. PATIENTS AND METHODS: Thirty-three consecutive patients
      without chronic obstructive pulmonary disease and with hypoxemic ARF (defined as
      severe dyspnea at rest, respiratory rate >30 breaths/min, PaO2:FiO2 < 200, and
      active contraction of the accessory muscles of respiration) were enrolled. Each
      patient treated with NPSV by helmet was matched with two controls with ARF
      treated with NPSV via a facial mask, selected by simplified acute physiologic
      score II, age, PaO2/FiO2, and arterial pH at admission. Primary end points were
      the improvement of gas exchanges, the need for endotracheal intubation, and the
      complications related to NPSV. RESULTS: The 33 patients and the 66 controls had
      similar characteristics at baseline. Both groups improved oxygenation after NPSV.
      Eight patients (24%) in the helmet group and 21 patients (32%) in the facial mask
      group (p = .3) failed NPSV and were intubated. No patients failed NPSV because of
      intolerance of the technique in the helmet group in comparison with 8 patients
      (38%) in the mask group (p = .047). Complications related to the technique (skin
      necrosis, gastric distension, and eye irritation) were fewer in the helmet group
      compared with the mask group (no patients vs. 14 patients (21%), p = .002). The
      helmet allowed the continuous application of NPSV for a longer period of time (p
      = .05). Length of stay in the intensive care unit, intensive care, and hospital
      mortality were not different. CONCLUSIONS: NPSV by helmet successfully treated
      hypoxemic ARF, with better tolerance and fewer complications than facial mask
      NPSV.

PMID- 11990924
TI  - Sedation modulates recognition of novel stimuli and adaptation to regular stimuli
      in critically ill adults.
AB  - BACKGROUND: Responsiveness of critically ill patients is affected by disease and
      by therapy. Subjective tests of responsiveness (e.g., modified Ramsay score)
      reflect global integrity of a response arc that includes transduction,
      perception, classification, and an overt response. The performance of individual
      components is usually not assessed. OBJECTIVE: To determine whether an
      association exists among sedative medications and the brain's component
      information processing and adaptive abilities. DESIGN: Initial observational
      study of a convenience sample. SETTING: A surgical intensive care unit of a
      university hospital. PATIENTS: A total of 22 endotracheally intubated,
      mechanically ventilated patients chemically sedated with narcotics and a
      benzodiazepine (n = 12), or narcotics and propofol (n = 10) using sedation
      protocols. INTERVENTIONS: None. MEASUREMENTS AND FINDINGS: Patients were
      presented flashes of light and pulses of sound at fixed or random intervals.
      Patients receiving low doses of fentanyl and propofol adapted to stimuli
      presented at fixed intervals and retained the response to novelty. Patients
      receiving higher doses of those medications did not respond to novelty and
      responded to stimuli presented at fixed intervals as if they were novel. Patients
      receiving fentanyl and benzodiazepines had generally weaker responses to all
      stimuli. Moreover, their responses to fixed and random stimuli were similar. At
      low doses, the patients retained responses to novelty and adapted to fixed,
      whereas at higher doses the opposite was observed: the response to novelty was
      lost and the patients responded to fixed stimuli as if they were novel. These
      observations suggest that the sedative medications generally accelerate the
      physiologic decay of stimuli as they engage the brain's information processing
      and adaptive abilities and further suggest that different sedative medications
      may have different effects on the brain. CONCLUSIONS: Commonly administered
      sedative medications may alter the brain's biophysical state and thereby modulate
      specific aspects of the brain's information processing and adaptive functions.
      These functions can be interrogated even when the patient is seemingly
      unresponsive. If this observation is confirmed in subsequent prospective
      controlled randomized trials, electrophysiologic interrogation of the brain's
      information processing and adaptive capacities could serve as an adjunct to
      clinical assessment of responsiveness and management of sedative medications.

PMID- 11990925
TI  - Administration of human inter-alpha-inhibitors maintains hemodynamic stability
      and improves survival during sepsis.
AB  - OBJECTIVES: The major forms of human inter-alpha-inhibitor proteins circulating
      in the plasma are inter-alpha-inhibitor (IalphaI, containing one light peptide
      chain called bikunin and two heavy chains) and pre-alpha-inhibitor (PalphaI,
      containing one light and one heavy chain). Although it has been reported that a
      decrease in IalphaI/PalphaI is correlated with an increased mortality rate in
      septic patients, it remains unknown whether administration of IalphaI/PalphaI
      early after the onset of sepsis has any beneficial effects on the cardiovascular
      response and outcome of the septic animal. The aim of this study, therefore, was
      to determine whether IalphaI and PalphaI have any salutary effects on the
      depressed cardiovascular function, liver damage, and mortality rate after
      polymicrobial sepsis. DESIGN: Prospective, controlled, randomized animal study.
      SETTING: A university research laboratory. SUBJECTS: Male adult rats were
      subjected to polymicrobial sepsis by cecal ligation and puncture or sham
      operation followed by the administration of normal saline (i.e., resuscitation).
      MEASUREMENTS AND MAIN RESULTS: At 1 hr after cecal ligation and puncture, human
      IalphaI/PalphaI at a dose of 30 mg/kg body weight or vehicle (normal saline, 1
      mL/rat) were infused intravenously over a period of 30 mins. At 20 hrs after
      cecal ligation and puncture (i.e., the late, hypodynamic stage of sepsis),
      cardiac output was measured by using a dye dilution technique, and blood samples
      were collected for assessing oxygen content. Oxygen delivery, consumption, and
      extraction ratio were determined. Plasma concentrations of liver enzymes alanine
      aminotransferase and aspartate aminotransferase as well as lactate and tumor
      necrosis factor-alpha also were measured. In additional animals, the necrotic
      cecum was excised at 20 hrs after cecal ligation and puncture with or without
      IalphaI/PalphaI treatment, and survival was monitored for 10 days thereafter. The
      results indicate that administration of human IalphaI/PalphaI early after the
      onset of sepsis maintained cardiac output and systemic oxygen delivery, whereas
      it increased oxygen consumption and extraction at 20 hrs after cecal ligation and
      puncture. The elevated concentrations of alanine aminotransferase, aspartate
      aminotransferase, tumor necrosis factor-alpha, and lactate were attenuated by
      IalphaI/PalphaI treatment. In addition, administration of human IalphaI/PalphaI
      improved the survival rate from 30% to 89% in septic animals at day 10 after
      cecal ligation and puncture and cecal excision. CONCLUSION: Human IalphaI/PalphaI
      appears to be a useful agent for maintaining hemodynamic stability and improving
      survival during the progression of polymicrobial sepsis.

PMID- 11990926
TI  - Changes in glucocorticoid and mineralocorticoid receptors of liver and kidney
      cytosols after pathologic stress and its regulation in rats.
AB  - OBJECTIVE: As effectors, glucocorticoid and mineralocorticoid receptors play an
      important role in pathologic stress. This study was designed to observe the
      changes in glucocorticoid receptor of liver cytosols and mineralocorticoid
      receptor of kidney cytosols after pathologic stress in rats. DESIGN: Controlled
      laboratory study. SETTING: Medical university. SUBJECTS: Male Wistar rats (weight
      range, 180-200 g). INTERVENTIONS: Rats received a low-degree or heavy-degree
      immersion scald that covered 10% or 35% total body surface area and were randomly
      divided to receive either tumor necrosis factor-alpha, interleukin-1beta
      polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, KPV
      peptide (Ac-D-Lys-L-Pro-D-Val), or saline (control). The binding capacity and the
      apparent dissociation constant of the steroid-binding sites of normal, low
      degree, and heavy-degree scalded rats were measured by radioligand-binding assay,
      with [3H]dexamethasone and aldosterone as the ligand, respectively. MEASUREMENTS
      AND MAIN RESULTS: The binding capacity of glucocorticoid receptor in hepatic
      cytosols in rats 12 hrs after heavy-degree scald (208.45 +/- 30.78 fmol/mg of
      protein) was lower than that of the control group (306.71 +/- 27.96 fmol/mg of
      protein; p < .01). The binding capacity of glucocorticoid receptor in hepatic
      cytosols in rats 12 hrs after low-degree scald (296.64 +/- 16.06 fmol/mg of
      protein) was not significantly different compared with the control group (p >
      .05). There were two types of mineralocorticoid receptor in kidney cytosols in
      rats, and their binding capacity and apparent dissociation constant were not
      identical. The binding capacity of mineralocorticoid receptor in rats 12 hrs
      after heavy-degree scald (binding capacity 1, 22.40 +/- 5.40 fmol/mg of protein;
      binding capacity 2, 196.30 +/- 32.50 fmol/mg of protein) was lower than that of
      the control group (binding capacity 1, 41.60 +/- 7.20 fmol/mg of protein; binding
      capacity 2, 317.60 +/- 70.00 fmol/mg of protein; p < .01). The binding capacity
      of mineralocorticoid receptor in kidney cytosols in rats 12 hrs after low-degree
      scald (binding capacity 1, 41.40 +/- 5.00 fmol/mg of protein; binding capacity 2,
      314.80 +/- 45.70 fmol/mg of protein) was not significantly different compared
      with the control group (p > .05). The injections of anti-rat tumor necrosis
      factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha
      melanocyte-stimulating hormone, and KPV peptide (Ac-D-Lys-L-Pro-D-Val) might
      prevent a reduction in the binding capacity of glucocorticoid receptor in hepatic
      cytosols and mineralocorticoid receptor in kidney cytosols in rats with heavy
      degree scald in vivo. CONCLUSIONS: These studies suggest that the glucocorticoid
      receptor of hepatic cytosols and the mineralocorticoid receptor of renal cytosols
      decreased in rats with heavy-degree immersion scald and that the injections of
      anti-rat tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing
      antibody, alpha-melanocyte-stimulating hormone, and KPV peptide might increase
      the level of glucocorticoid receptor and mineralocorticoid receptor in vivo.

PMID- 11990927
TI  - Effect of histamine H3 receptor blockade on venous return and splanchnic
      hemodynamics in experimental bacteremia.
AB  - OBJECTIVE: In the heart, histamine H3 receptors may function as inhibitory
      presynaptic receptors that decrease adrenergic neural norepinephrine release in
      conditions of enhanced sympathetic tone. In a previous study, we found that H3
      receptor blockade improved cardiac contractility and systemic hemodynamics in
      experimental bacteremia in dogs. Because histamine H3 receptors have been found
      in the splanchnic circulation in other animal models, it was not clear the extent
      to which H3 receptor blockade may have altered splanchnic hemodynamics, and
      variables of venous return, that in turn contributed to the overall improvement
      in systemic hemodynamics observed in the previous experiment. In the present
      study, we examined splanchnic hemodynamics in the presence of H3 receptor
      blockade in a canine model of Escherichia coli bacteremia. DESIGN: Bacteremia was
      produced by intravenous infusion of live E. coli administered throughout the
      experiment. Variables of venous return included mean systemic pressure,
      resistance to venous return, and mean right atrial pressure. Splanchnic
      measurements included hepatic and portal pressures and flows. Measurements were
      obtained before and after H3 receptor blockade with thioperamide maleate. The
      animals were studied while ventilated and anesthetized. RESULTS: H3 receptor
      blockade caused a decrease in mean right atrial pressure from 5.9 mm Hg
      pretreatment to 3.5 mm Hg posttreatment (p < .05), although it did not affect
      mean systemic pressure or resistance to venous return. There were no changes in
      portal or hepatic flows after H3 receptor blockade. The cardiac function curve
      after H3 receptor blockade was shifted upward and to the left compared with the
      pretreatment curve. CONCLUSIONS: The results showed that the primary effect of H3
      receptor blockade in experimental bacteremia was attributable to an increase in
      inotropy. There was no evidence to indicate that H3 receptor activation
      contributed to altered splanchnic hemodynamics in this model.

PMID- 11990928
TI  - Global brain water increases after experimental focal cerebral ischemia: effect
      of hypertonic saline.
AB  - OBJECTIVE: Isolated experiments suggest that global cerebral edema is a sequela
      of large hemispheric ischemic lesions, presumably as an extension of the initial
      ischemic insult into areas of vital, noninjured tissue. Diuretics and osmotic
      agents are controversial and poorly defined therapeutic modalities after large
      infarction. By using a rat model of middle cerebral artery occlusion (MCAO), we
      tested the hypothesis that significant edema occurs in the contralateral
      uninjured hemisphere and that this postischemic complication can be manipulated
      by hypertonic saline therapy. DESIGN: Prospective laboratory animal study.
      SETTING: Research laboratory in a teaching hospital. SUBJECTS: Halothane
      anesthetized, male Wistar rats. INTERVENTIONS: Under controlled conditions of
      normoxia, normocarbia, and normothermia, rats were subjected to 2 hrs of MCAO.
      MEASUREMENTS AND MAIN RESULTS: Adequacy of MCAO and reperfusion was assessed by
      laser Doppler flowmetry. All animals except naive rats received continuous
      infusion of 0.9% saline at 0.5 mL/hr throughout the experiment. Brains were
      harvested, and tissue water content was estimated by comparing the wet-to-dry
      weight ratios of ipsilateral and contralateral cerebral hemispheres at 12 hrs, 24
      hrs, or 2, 3, or 7 days postischemia. Naive and sham-operated rats served as
      control cohorts. In a second series of randomized experiments, wet-to-dry weight
      ratios were determined in rats treated with continuous intravenous infusion of
      7.5% hypertonic saline (0.5 mL/hr; acetate/chloride, 50:50) and were compared
      with well-studied antiedema therapy: 20% mannitol (2.5 g/kg bolus every 6 hrs) or
      furosemide (2.5 mg/kg bolus every 6 hrs). Treatments were started at 24 hrs of
      reperfusion, and brain water was assessed at 2 days of reperfusion. In a third
      series of experiments, wet-to-dry ratios were determined in brains harvested at 2
      days of reperfusion from rats that were subjected to 2 hrs of MCAO and did not
      receive any intravenous fluids. All values are mean +/- SEM. There were no
      differences between sham-operated and naive control cohorts. At 24 hrs of
      reperfusion, water content was higher in both ipsilateral ischemic (82.80 +/-
      0.86%) and contralateral hemispheres (80.53 +/- 0.29%), compared with naive
      animals (ipsilateral, 79.62 +/- 0.12%; contralateral, 79.53 +/- 0.13%). Maximal
      cerebral edema was measured at 2 days in both hemispheres (ipsilateral, 83.94 +/-
      0.47%; contralateral, 80.63 +/- 0.13%). Edema was present for up to 3 days in
      contralateral tissue (80.27 +/- 0.26%) and persisted to 7 days in the injured
      hemisphere (81.07 +/- 0.34%). Maximal edema (as assessed at 2 days postocclusion)
      was robustly attenuated with hypertonic saline therapy (ipsilateral, 81.59 +/-
      0.52%; contralateral, 78.44 +/- 0.22%). The efficacy of hypertonic saline was
      equivalent to furosemide (ipsilateral, 82.09 +/- 0.50%; contralateral, 79.13 +/-
      0.17%) but less robust than mannitol (ipsilateral, 79.89 +/- 0.36%;
      contralateral, 78.73 +/- 0.17%). CONCLUSIONS: These data demonstrate that
      cerebral edema persists in both injured and contralateral hemispheres for days
      after MCAO. The global, maximal increase in brain water is responsive to
      continuous 7.5% hypertonic saline treatment begun at 24 hrs postischemia and to
      standard diuretic/osmotic agents. These results may have implications for
      diuretic and osmotic therapy in clinical ischemic stroke.

PMID- 11990929
TI  - Nitric oxide-derived nitrate anion contributes to endotoxic shock and multiple
      organ injury/dysfunction.
AB  - OBJECTIVE: Because nitrate represents the major end-product of nitric oxide in
      vivo and can affect enzyme activity, cell electrophysiological functions, and
      cell membrane integrity, we hypothesized that overaccumulated nitric oxide
      derived nitrate anion in tissues or organs in vivo may contribute to endotoxic
      shock and multiple organ injury/dysfunction during endotoxemia. DESIGN:
      Prospective, experimental animal study. SETTING: Laboratory at a university
      hospital. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Rats were injected
      intraperitoneally with 5, 10, or 20 mg/kg lipopolysaccharide or saline and were
      studied in groups at 0, 6, 12, and 24 hrs. MEASUREMENTS AND MAIN RESULTS:
      Significant differences were seen between nitrate concentrations in the heart,
      lung, kidney, liver, brain, aorta, diaphragm, spleen, thymus, testis or ovary,
      hind limb muscle, intestine, adipose tissue, bone, bladder, urine and plasma,
      which imply a nitrate gradient between intracellular and extracellular
      compartments. Lipopolysaccharide significantly increased nitrate concentration at
      12 hrs in most tissues and organs, except in the brain, adipose tissue, and
      muscle. It increased more in plasma than in tissues. The lipopolysaccharide dose
      dependent nitrate concentration was observed only in the aorta and lungs. The
      nitrate concentration change was paralleled by the systemic inflammatory response
      syndrome, as indicated by alterations of myeloperoxidase activity and by impaired
      histologic and cellular membrane integrity in tissues and organs. Mean arterial
      pressure was negatively correlated with nitrate concentration modifications in
      the aorta during 24 hrs of endotoxemia. CONCLUSIONS: These results collectively
      indicate that overaccumulated nitric oxide-derived nitrate anion in tissues or
      organs in vivo contributes to endotoxic shock and multiple organ
      injury/dysfunction during endotoxemia.

PMID- 11990930
TI  - Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure
      treated with a bioartificial liver containing alginate-entrapped hepatocytes.
AB  - OBJECTIVE: To analyze the effects of an extracorporeal bioartificial liver
      containing alginate bead-entrapped hepatocytes on pigs with ischemia-induced
      acute hepatic failure. DESIGN: Prospective animal study. SETTING: University and
      INSERM laboratory. SUBJECTS: Fifteen Large White/Pietrin female pigs weighing 20
      30 kg. INTERVENTIONS: Acute hepatic failure was induced by end-to-side portocaval
      shunt and ligature of the whole porta hepatitis. The bioartificial liver was in a
      thermostabilized column, containing a fluidized bed of alginate beads that
      embedded porcine hepatocytes, connected to a plasmapheresis system. Intracranial
      pressure; survival; ammonia, total bilirubin, aminotransferases, alkaline
      phosphatase, and lactate concentrations; and clotting factors were studied. The
      groups were pigs with acute hepatic failure (group 1, n = 4), pigs with acute
      hepatic failure treated with bioartificial liver containing empty beads (group 2,
      n = 4), or porcine hepatocytes (group 3, n = 5). MEASUREMENTS AND MAIN RESULTS:
      In group 1, survival of pigs averaged 10.9 +/- 1.0 hrs; intracranial pressure
      reached 32.3 +/- 3.8 mm Hg and was associated with coma and cerebral edema. After
      connection to the bioartificial liver, the survival of acute hepatic failure pigs
      was 12.1 +/- 1.4 hrs in group 2 and 14.8 +/- 2.5 hrs in group 3. In group 3,
      intracranial pressure and bilirubin concentrations were reduced significantly
      compared with both group 1 and group 2. Neither signs of encephalopathy nor
      cerebral edema was observed in any animal of group 3. In all animals, plasma
      ammonium, aminotransferases, alkaline phosphatase, and lactate concentrations
      increased and clotting factors decreased with no significant differences between
      the three groups. Autopsy revealed a total necrosis of the liver, which was
      histologically confirmed. CONCLUSIONS: The ischemia-induced model of acute
      hepatic failure in pigs is reproducible and provides measurable clinical and
      biological features. A bioartificial liver containing alginate bead-entrapped
      hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced
      acute hepatic failure, suggesting that the bioartificial liver can clear out
      toxic compounds that are released from necrotic livers.

PMID- 11990931
TI  - Can the interleukin-6 response to endotoxin be predicted? Studies of the
      influence of a promoter polymorphism of the interleukin-6 gene, gender, the
      density of the endotoxin receptor CD14, and inflammatory cytokines.
AB  - OBJECTIVES: To evaluate whether the -174 G/C promoter polymorphism of the
      interleukin-6 gene, gender, the monocyte density of the endotoxin receptor CD14,
      or the inflammatory cytokines tumor necrosis factor-alpha or interleukin-1beta
      influence the interleukin-6 response of whole blood to endotoxin. DESIGN:
      Analysis of interleukin-6 release from endotoxin-stimulated human whole blood.
      SETTING: Medical research laboratory. PATIENTS: Healthy human blood donors.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The interleukin-6 -174 G/C
      and the tumor necrosis factor -308 G/A promoter polymorphisms were determined by
      real-time polymerase chain reaction assay by using specific fluorescence labeled
      hybridization probes. Monocyte CD14 expression was assessed by flow cytometry.
      After incubation of whole blood with endotoxin, plasma concentrations of
      interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta were measured
      by means of chemiluminescence. The interleukin-6 concentrations were lower (p =
      .005) in individuals who were CG heterozygotes compared with individuals
      homozygous for the C or the G. The difference between C and G homozygotes was not
      significant (p = .67). The interleukin-6 response was enhanced in men compared
      with women (p = .015). There was no correlation between interleukin-6
      concentrations and monocyte CD14 density. Interleukin-6 concentrations correlated
      with the concentrations of tumor necrosis factor-alpha (r = .59, p = .01) and
      interleukin-1beta (r = .47, p = .01). There was no linkage between the tumor
      necrosis factor -308 and the interleukin-6 -174 polymorphisms. CONCLUSIONS: The
      interleukin-6 response to endotoxin was influenced by gender and correlated with
      the concentrations of more proximal cytokine tumor necrosis factor-alpha and
      interleukin-1beta. The interleukin-6 -174 G/C promoter polymorphism can only
      partly predict the interleukin-6 response of human whole blood to endotoxin
      stimulation, and the results were different from previous reporter gene assays
      that reported higher interleukin-6 concentrations for the G allele. Tumor
      necrosis factor -308 G homozygotes produce the lowest tumor necrosis factor
      concentrations. The number of tumor necrosis factor -308 G homozygotes was not
      higher among interleukin-6 -174 heterozygotes, and thus this cannot account for
      their significantly smaller interleukin-6 production.

PMID- 11990932
TI  - Neutrophils and platelets accumulate in the heart, lungs, and kidneys after
      cardiopulmonary bypass in neonatal pigs.
AB  - OBJECTIVE: Cardiac surgery with cardiopulmonary bypass elicits a systemic
      inflammatory response. An exaggerated response is associated with organ
      dysfunction and increased morbidity and mortality. DESIGN: The aim of the present
      study was to investigate whether the cardiopulmonary bypass procedure in itself
      results in accumulation of isotope-labeled platelets, polymorphonuclear
      neutrophils, and fibrinogen at organ levels in neonatal pigs and to monitor
      changes in organ function. SETTING: Pediatric cardiopulmonary bypass setup with
      60 mins of aortic cross-clamp time and 120 mins of hypothermic cardiopulmonary
      bypass time. SUBJECTS: Thirty piglets were allocated to sternotomy alone (sham
      group, n = 15) or to sternotomy and cardiopulmonary bypass (n = 15). MEASUREMENTS
      AND MAIN RESULTS: Isotope-labeled autologous polymorphonuclear neutrophils,
      platelets, and commercially available fibrinogen were infused, and the specific
      accumulation at organ level was measured in a gamma counter 4 hrs after
      termination of cardiopulmonary bypass. Concomitant changes in oxygenation index
      and cardiac output were registered. Animals exposed to cardiopulmonary bypass
      showed a significantly higher technetium-99m-polymorphonuclear neutrophil
      accumulation in the lungs and kidneys, whereas indium-111-platelets accumulated
      in the heart and kidneys compared with the sham group. There was a significantly
      larger increase in oxygenation index and significantly larger decrease in cardiac
      output between the pre- and postcardiopulmonary bypass period in the
      cardiopulmonary bypass group compared with the sham group. CONCLUSIONS: The
      cardiopulmonary bypass procedure without cardiac surgery elicits organ
      dysfunction in terms of impaired respiratory and hemodynamic function. Platelets
      and polymorphonuclear neutrophils were entrapped in the heart, lungs, and kidneys
      of cardiopulmonary bypass animals, indicating that cell accumulation may
      contribute to the developing organ dysfunction.

PMID- 11990933
TI  - Adherence of yeast and filamentous forms of Candida albicans to cultured
      enterocytes.
AB  - OBJECTIVE: Systemic candidiasis is a major cause of complicating infections in
      intensive care units. Morbidity and mortality are high, even in those who receive
      appropriate antifungal therapy. Because the intestinal tract is considered a
      major portal of entry for systemic candidiasis, experiments were designed to
      clarify the ability of yeast and filamentous forms, as well as the INT1 gene
      product, to influence adherence of Candida albicans to the intestinal epithelium.
      DESIGN: Controlled. SETTING: University teaching hospital research laboratory.
      SUBJECTS: Mature Caco-2 and HT-29 cultured enterocytes. INTERVENTIONS: C.
      albicans INT1 mutant strains, defective in filament production, were used to
      observe the ultrastructural surface interactions of C. albicans with cultured
      intestinal epithelial cells, namely Caco-2 and HT-29 cells. These mutant strains
      also were used to quantify the effect of the INT1 gene product on C. albicans
      adherence (yeast and filamentous forms) to cultured enterocytes. Ultrastructural
      surface interactions of C. albicans with cultured enterocytes were observed with
      high resolution scanning electron microscopy. C. albicans adherence to cultured
      enterocytes was quantified by using a colorimetric enzyme-linked immunosorbent
      assay. MEASUREMENTS AND MAIN RESULTS: Both yeast and filamentous forms of C.
      albicans appeared tightly adherent to the apical surface of cultured enterocytes,
      and INT1 appeared to have little, if any, effect on these ultrastructural surface
      interactions. The distal ends of C. albicans filaments appeared to mediate
      adherence to enterocyte apical microvilli, and thigmotropism (contact guidance)
      appeared to play a role in C. albicans adherence. The absence of functional INT1
      was associated with decreased adherence of C. albicans yeast forms to cultured
      enterocytes. CONCLUSIONS: Although functional INT1 appeared to facilitate
      adherence of C. albicans yeast forms to cultured enterocytes, the role of INT1 in
      adherence of filamentous forms was unclear, and both yeast and filamentous forms
      could adhere to, and perhaps invade, the apical surface of cultured enterocytes.

PMID- 11990934
TI  - Complement activation alters myocellular sodium homeostasis during polymicrobial
      sepsis.
AB  - OBJECTIVE: To determine whether complement activation alters sodium homeostasis
      in fast-twitch skeletal muscles during sepsis, and if protein kinase-C is
      involved in this process. DESIGN: Prospective, randomized, controlled animal
      study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats weighing
      60-75 g. INTERVENTIONS: Rats underwent cecal ligation and puncture (CLP) or sham
      operation with or without soluble complement receptor-1 treatment. Soluble
      complement receptor-1 (20 mg/kg) was administered intraperitoneally 5 mins before
      operation. Twenty-four hours after operation, fast-twitch extensor digitorum
      longus muscles were isolated and incubated in normal Krebs-Henseleit buffer (pH
      7.4). In addition, extensor digitorum longus muscles isolated from normal rats
      were incubated for 1 hr in the Krebs-Henseleit buffer media containing normal rat
      sera, zymosan-activated (4 or 10 mg/mL) rat sera, or heat-inactivated rat sera.
      Ten percent diluted rat sera were used as a complement source in all groups.
      Last, extensor digitorum longus muscles isolated from normal rats were incubated
      for 1 hr in the Krebs-Henseleit buffer media containing zymosan-activated or heat
      inactivated rat sera in the presence of protein kinase-C inhibitors (i.e., 4
      microM GF109203X or 5 microM rottlerin). Soluble C5b-9 complex concentrations in
      zymosan-activated human sera were determined by enzyme-linked immunosorbent assay
      to evaluate the degree of complement activation induced by zymosan. MEASUREMENTS
      AND MAIN RESULTS: Incubated extensor digitorum longus muscles from CLP, sham
      operated, or normal rats were used to measure intracellular Na+ and K+ contents
      ([Na+]i or [K+]i). Polymicrobial sepsis, as produced by CLP, markedly increased
      [Na+]i and [Na+]i/[K+]i ratios in fast-twitch extensor digitorum longus muscles
      24 hrs after CLP compared with sham operation. Administration of soluble
      recombinant complement receptor 1 before operation significantly decreased
      myocellular [Na+]i and [Na+]i/[K+]i ratios. Zymosan profoundly elevated soluble
      C5b-9 concentrations in human sera in vitro. Sublytic zymosan-activated rat sera
      significantly increased myocellular [Na+]i and [Na+]i/[K+]i ratios relative to
      heat-inactivated rat sera. No difference in myocellular [Na+]i and [Na+]i/[K+]i
      ratios was observed when we used 4 mg/mL compared with 10 mg/mL of zymosan for
      activation. Last, incubation of extensor digitorum longus muscles with GF109203X
      or rottlerin significantly attenuated increases in myocellular [Na+]i and
      [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera. CONCLUSIONS:
      Polymicrobial sepsis alters sodium homeostasis in fast-twitch skeletal muscles,
      which is significantly attenuated by administration of soluble complement
      receptor 1. Protein kinase-C inhibition completely blocks changes in myocellular
      [Na+]i and [Na+]i/[K+]i ratios induced by sublytic zymosan-activated rat sera.
      Collectively, these results suggest that an inappropriate activation of
      complement is, at least in part, responsible for changes in skeletal muscle
      sodium homeostasis during sepsis, and activation of PKC is one of the
      intracellular signaling pathways by which complement activation alters
      myocellular sodium homeostasis.

PMID- 11990935
TI  - Successful management of severe respiratory failure combining heliox with
      noninvasive high-frequency percussive ventilation.
AB  - Heliox has been shown to be beneficial in the management of different obstructive
      pulmonary disorders. High-frequency percussive ventilation has recently been
      advocated to treat lung injury in children with reduced lung compliance. We
      report our experience of combining heliox with noninvasive high-frequency
      percussive ventilation in a 5-yr-old boy with severe acute respiratory failure
      resulting from advanced cystic fibrosis lung disease. The dramatic improvement
      allowed stabilization and withholding of endotracheal intubation. We hypothesize
      that this approach improved gas exchange by enhancing molecular diffusion and by
      favoring laminar flow throughout the upper and lower airways. Further
      investigations should study the mechanisms of this noninvasive bimodal therapy.

PMID- 11990936
TI  - Right upper lobe pulmonary edema after mitral valve replacement caused by
      paravalvular leakage recognized by bedside transesophageal echocardiography.
AB  - OBJECTIVE: To describe an unusual case of right upper lobe pulmonary edema caused
      by acute paravalvular leakage that was identified by the use of bedside
      transesophageal echocardiography. DESIGN: Case report. SETTING: University
      affiliated hospital. PATIENT: A 59-yr-old male patient underwent prosthetic
      mitral valve replacement (St. Jude valve) for severe mitral regurgitation and
      developed sudden onset of dyspnea and change in consciousness with blood pressure
      decreased to 70/30 mm Hg. Elevation of central venous pressure and images of
      transthoracic echocardiography led to the diagnosis of cardiac tamponade.
      CONCLUSION: Acute paravalvular leakage after mitral valvular replacement should
      be considered as one of the differential diagnoses for unilateral pulmonary
      edema. Physical findings of a holosystolic murmur and findings from bedside
      transesophageal echocardiography can confirm the diagnosis, avoiding delay in
      management.

PMID- 11990937
TI  - Massive hemothorax after removal of subclavian vein catheter: a very unusual
      complication.
AB  - A case of massive hemothorax developing a few minutes after removal of a central
      venous catheter is described in a 51-yr-old woman, who had undergone a renal
      transplant. The patient had an arteriovenous fistula for hemodialysis on the same
      side as the central catheter. The mechanism of the onset of this complication is
      discussed. We recommend avoiding positioning a central catheter on the same side
      as an arm arteriovenous fistula. Furthermore, we think it is necessary to monitor
      patients after removal, as is usually done after positioning, to detect this
      potentially fatal complication.

PMID- 11990938
TI  - Cardiac tamponade in an orthotopic liver recipient with pulmonary hypertension.
AB  - OBJECTIVE: To describe the clinical, hemodynamic, and echocardiographic findings
      of cardiac tamponade in a patient with portopulmonary hypertension shortly after
      orthotropic liver transplantation. DESIGN: Case report. SETTING: Surgical
      intensive care unit of a university teaching hospital. PATIENT: One patient with
      portopulmonary hypertension deteriorated progressively after orthotropic liver
      transplantation and developed cardiogenic shock. INTERVENTION: Serial
      transthoracic echocardiography showed increased right ventricular pressures and
      pericardial effusion without evidence of cardiac tamponade. Since right
      ventricular diastolic collapse may not be present in the setting of pulmonary
      hypertension and her clinical scenario was consistent with tamponade,
      pericardiocentesis was performed. MEASUREMENTS AND MAIN RESULTS: There was
      dramatic improvement of the clinical, hemodynamic, and echocardiographic
      variables after pericardiocentesis CONCLUSION: Pulmonary hypertension may
      decrease the predictive accuracy of echocardiographic clues for cardiac
      tamponade. Pericardiocentesis should be considered with clinical suspicion of
      cardiac tamponade without classic echocardiographic evidence in portopulmonary
      hypertension.

PMID- 11990939
TI  - Endocrine support in the critically ill.

PMID- 11990940
TI  - Surviving intensive care.

PMID- 11990941
TI  - Arginine in shock, trauma, and sepsis.

PMID- 11990942
TI  - Definition of sepsis: not quite time to dump SIRS?

PMID- 11990943
TI  - Intensive care unit sleep disruption: can the cycle be restored?

PMID- 11990944
TI  - Dexanabinol as a treatment for traumatic brain injury: will another therapeutic
      promise be broken?

PMID- 11990945
TI  - Continuous measurement of cerebral blood flow velocity by using transcranial
      Doppler reveals significant moment-to-moment variability of data in healthy
      volunteers and in patients.

PMID- 11990946
TI  - Comparing therapies and outcomes: mirror, mirror on the wall.

PMID- 11990947
TI  - Is enteral feeding for everyone?

PMID- 11990948
TI  - Humoral products from tumor necrosis factor-alpha-stimulated neutrophils suppress
      neutrophil function: shedding new light on paracrine signaling.

PMID- 11990949
TI  - Understanding sepsis: promise, caution, and accolades to a mentor's mentor.

PMID- 11990950
TI  - Specific therapies for inhalation injury.

PMID- 11990951
TI  - Is nitrate anion a mediator of organ system injury in rats injected with
      lipopolysaccharide?

PMID- 11990952
TI  - Diagnosis of cardiac tamponade in the presence of complex medical illness.

PMID- 11990953
TI  - Some remarks on choosing a method for outcome prediction.

PMID- 11990954
TI  - Arthropods and invertebrates allergy (with the exclusion of mites): the concept
      of panallergy.

PMID- 11990955
TI  - Xenotransplantation: promising advances cause excitement, uneasiness.

PMID- 11990956
TI  - Veterinary, equine community dispel accusations against the pregnant mare urine
      industry.

PMID- 11990957
TI  - Questions study on Escherichia coli susceptibility.

PMID- 11990958
TI  - The use and abuse of Aesculapian authority in veterinary medicine.

PMID- 11990959
TI  - What is your diagnosis? A 2.0 x 1.75-cm well-circumscribed ovoid mineralized
      opacity over the left mandible.

PMID- 11990960
TI  - ECG of the month. Electrical alternans possibly secondary to pericardial
      effusion.

PMID- 11990961
TI  - Veterinary income per hour, 1999.

PMID- 11990962
TI  - Clinical evaluation of dietary modification for treatment of spontaneous chronic
      renal failure in dogs.
AB  - OBJECTIVE: To determine whether a diet used for dogs with renal failure (renal
      food [RF]) was superior to an adult maintenance food (MF) in minimizing uremic
      crises and mortality rate in dogs with spontaneous chronic renal failure. DESIGN:
      Double-masked, randomized, controlled clinical trial. ANIMALS: 38 dogs with
      spontaneous chronic renal failure. PROCEDURE: Dogs were randomly assigned to a
      group fed adult MF or a group fed RF and evaluated for up to 24 months. The 2
      groups were of similar clinical, biochemical, and hematologic status. The effects
      of diets on uremic crises and mortality rate were compared. Changes in renal
      function were evaluated by use of serial evaluation of serum creatinine
      concentrations and reciprocal of serum creatinine concentrations. RESULTS:
      Compared with the MF, the RF had a beneficial effect regarding uremic crises and
      mortality rate in dogs with mild and moderate renal failure. Dogs fed the RF had
      a slower decline in renal function, compared with dogs fed the MF. CONCLUSIONS
      AND CLINICAL RELEVANCE: Dietary modifications are beneficial in minimizing
      extrarenal manifestations of uremia and mortality rate in dogs with mild and
      moderate spontaneous chronic renal failure. Results are consistent with the
      hypothesis that delay in development of uremic crises and associated mortality
      rate in dogs fed RF was associated, at least in part, with reduction in rate of
      progression of renal failure.

PMID- 11990963
TI  - Comparison of radiography, computed tomography, and magnetic resonance imaging
      for evaluation of appendicular osteosarcoma in dogs.
AB  - OBJECTIVE: To determine which imaging modality best determines the microscopic
      extent of primary appendicular osteosarcoma in amputated limbs in dogs. DESIGN:
      Case series. ANIMALS: 10 dogs with appendicular osteosarcoma. PROCEDURE: 10 dogs
      with appendicular osteosarcoma that did not receive neoadjuvent chemotherapy were
      treated by use of limb amputation. Amputated limbs were imaged by use of
      radiography, computed tomography (CT), and magnetic resonance imaging (MRI) and
      examined microscopically to determine longitudinal extent of neoplastic cell
      involvement and length of associated intramedullary fibrosis. Changes detected by
      use of the various imaging studies were compared with the actual tumor length
      determined microscopically. Data were analyzed to determine which imaging
      technique most closely predicted tumor length. RESULTS: Measurements obtained by
      use of craniocaudal radiographic views were most accurate at predicting tumor
      length but underestimated tumor length substantially in 1 limb and slightly in
      another limb. Measurements made by use of CT were most accurate at predicting
      tumor length when intramedullary fibrosis was taken into account but
      underestimated tumor length in 1 limb. Measurements made by use of MRI were least
      accurate but did not underestimate tumor length in any of the limbs. CONCLUSIONS
      AND CLINICAL RELEVANCE: Although radiography is used in diagnosis of osteosarcoma
      in dogs, additional imaging studies to confirm the extent of neoplasia prior to
      limb-sparing ostectomy may be beneficial. Underestimation of tumor length would
      be associated with higher incidence of incomplete excision and local tumor
      recurrence.

PMID- 11990964
TI  - Interobserver variation among histopathologic evaluations of intestinal tissues
      from dogs and cats.
AB  - OBJECTIVE: To determine whether substantial interobserver variation exists among
      diagnostic pathologists for descriptions of intestinal mucosal cell populations
      and whether histopathologic descriptions accurately predict when a patient does
      not have clinically evident intestinal disease. DESIGN: Comparative survey.
      Sample Population-14 histologic slides of duodenal, ileal, or colonic tissue from
      10 dogs and 3 cats. PROCEDURE: Each histologic slide was evaluated independently
      by 5 pathologists at 4 institutions. Pathologists, who had no knowledge of the
      tissues' origin, indicated whether slides were adequate for histologic evaluation
      and whether the tissue was normal or abnormal. They also identified the main
      infiltrating cell type in specimens that were considered abnormal, and whether
      infiltrates were mild, moderate, severe, or neoplastic. RESULTS: Quality of all
      slides was considered adequate or superior by at least 4 of the 5 pathologists.
      For intensity of mucosal cellular infiltrates, there was uniformity of opinion
      for 1 slide, near-uniformity for 6 slides, and nonuniformity for 7 slides. Five
      dogs did not have clinical evidence of intestinal disease, yet the pathologists'
      descriptions indicated that their intestinal tissue specimens were abnormal.
      CONCLUSIONS AND CLINICAL RELEVANCE: Substantial interobserver variation was
      detected. Standardization of pathologic descriptions of intestinal tissue is
      necessary for meaningful comparisons with published articles. Clinicians must be
      cautious about correlating clinical signs and histopathologic descriptions of
      intestinal biopsy specimens.

PMID- 11990965
TI  - Subclinical exocrine pancreatic insufficiency in dogs.
AB  - OBJECTIVE: To study progression of autoimmune-mediated atrophic lymphocytic
      pancreatitis from the subclinical to the clinical phase (exocrine pancreatic
      insufficiency [EPI]) and determine whether progression of the disease could be
      halted by treatment with immunosuppressive drugs. DESIGN: Randomized controlled
      trial. ANIMALS: 20 dogs with subclinical EPI. PROCEDURE: Diagnosis of subclinical
      EPI was determined on the basis of repeatedly low serum trypsin like
      immunoreactivity (TLI) in dogs with no signs of EPI. Laparotomy was performed on
      12 dogs with partial acinar atrophy and atrophic lymphocytic pancreatitis. A
      treatment group (7 dogs) received an immunosuppressive drug (azathioprine) for 9
      to 18 months, and a nontreatment group (13) received no medication. RESULTS:
      During the subclinical phase, serum TLI was repeatedly low (< 5.0 microg/L).
      Although a few dogs had nonspecific gastrointestinal tract signs, they did not
      need diet supplementation with enzymes. While receiving immunosuppressive
      medication, treated dogs had no clinical signs of EPI, but within 2 to 6 months
      after treatment was stopped, 2 dogs had signs of EPI, and diet supplementation
      with enzymes was started. Five of the 13 untreated dogs needed diet
      supplementation with enzymes within 6 to 46 months. During follow-up of 1 to 6
      years, 3 of the 7 treated dogs and 8 of the 13 untreated dogs did not need
      continuous diet supplementation with enzymes. CONCLUSIONS AND CLINICAL RELEVANCE:
      Progression of atrophic lymphocytic pancreatitis varied widely. The subclinical
      phase may last for years and sometimes for life. The value of early treatment
      with an immunosuppressive drug was questionable and, because of the slow natural
      progression of the disease, cannot be recommended.

PMID- 11990966
TI  - Duodenal obstruction caused by infection with Pythium insidiosum in a 12-week-old
      puppy.
AB  - Pythium insidiosum is an aquatic fungus-like organism that causes a serious
      chronic granulomatous disease called pythiosis in animals and humans in tropical
      and subtropical regions of the world. In North America, pythiosis is most often
      diagnosed in the Gulf Coast states. Early recognition of the disease is crucial
      to successful treatment, which includes surgical resection of granulomatous
      lesions and administration of antifungal agents. Despite increasing availability
      of diagnostic tests, intestinal pythiosis is insidious and is often not detected
      until lesions are extensive. Intestinal pythiosis was diagnosed in a 12-week-old
      puppy from South Carolina examined because of vomiting, diarrhea, and anorexia.
      Pythiosis was not initially suspected because of the young age of the patient and
      because pythiosis is uncommon in this area.

PMID- 11990967
TI  - Use of a carbon dioxide laser for surgical management of cutaneous masses in
      horses: 32 cases (1993-2000).
AB  - OBJECTIVE: To determine outcome of horses in which cutaneous masses were removed
      with a carbon dioxide laser. DESIGN: Retrospective study. ANIMALS: 32 horses.
      PROCEDURE: Medical records of horses with 1 or more cutaneous masses treated with
      a carbon dioxide laser were examined. Follow-up information was obtained through
      telephone interviews with owners and referring veterinarians. RESULTS: Cutaneous
      masses were classified as sarcoids (15 horses), neoplastic masses other than
      sarcoids (squamous cell carcinoma [91; fibroma [1]; and melanoma [1]), and
      nonneoplastic masses (6). Minimum follow-up time was 6 months. Five sarcoids and
      2 squamous cell carcinomas recurred. Seven (21%) horses had complications
      associated with dehiscence of wounds that had been closed primarily or failure of
      wound healing because of recurrence of the mass. Twenty-six (81%) owners were
      satisfied with the cosmetic appearance following surgery. CONCLUSION AND CLINICAL
      RELEVANCE: Results suggest that a carbon dioxide laser may be effective for
      treatment of cutaneous masses in horses.

PMID- 11990968
TI  - Diagnosis, surgical treatment, and performance after unilateral castration in
      breeding bulls: 21 cases (1989-1999).
AB  - OBJECTIVE: To evaluate signalment, surgical treatment, postoperative
      complications, and future breeding success or semen production in a group of
      bulls with naturally occurring disease of the scrotum or testis. STUDY DESIGN:
      Retrospective study. ANIMALS: 21 bulls that underwent unilateral castration after
      evaluation for scrotal swelling. PROCEDURE: A computer-assisted search of medical
      records at 2 veterinary teaching hospitals was performed. Historical, diagnostic,
      surgical, and follow-up data were collected and analyzed for those bulls with
      scrotal swelling that underwent unilateral castration. RESULTS: Four of 5 pasture
      breeding bulls and 9 of 10 semen collection-center bulls successfully bred cows
      or produced viable semen within 6 months of surgery. Fourteen of 21 surgical
      procedures were performed after induction of general anesthesia. Sixty-six
      percent of procedures were performed as open castrations. Seventy-one percent of
      bulls developed postoperative complications, most of which were mild swellings.
      Unilateral castration returned 13 of 15 bulls with unilateral disease of the
      scrotum or testis to productive service by 6 months after surgery. CONCLUSION AND
      CLINICAL RELEVANCE: Unilateral castration is an effective treatment for
      unilateral disease of the,scrotum or testis in bulls, allowing return to
      reproductive function.

PMID- 11990969
TI  - Nonlethal clinical techniques used in the diagnosis of diseases of fish.
AB  - Numerous nonlethal clinical techniques can be used on live fish to yield valuable
      diagnostic information. These techniques include skin, fin, and gill biopsies;
      bacteriologic cultures of gill or skin lesions; tissue and fluid aspiration; and
      radiography Most techniques can be performed on live fish without the use of
      anesthesia, although light sedation of the fish often simplifies the procedure,
      making the procedure more easily accomplished and less stressful on the fish.
      Because water conditions have a considerable effect on the health and well-being
      of aquatic animals, an in-house evaluation of water quality (eg, temperature, pH,
      ammonia, nitrites, nitrates, and salinity) is also paramount to any clinical
      diagnostic evaluation. As with domestic animals, a complete and accurate history
      and thorough external examination are prerequisite to the selection of
      appropriate diagnostic techniques as well as the formulation of any management or
      therapeutic plan. Through the correlation of clinical history, water quality
      variables, and results of diagnostic testing, an informed plan of action can be
      devised to correct acute or chronic problems in aquatic animals.

PMID- 11990970
TI  - Measuring sexual preferences in virtual reality: a pilot study.
AB  - Virtual reality (VR), as a method to assess sexual preferences, is explored.
      Dynamics of the subjective point of view (POV), subjective affective state, and
      feeling of presence, as measured following the interaction with a virtual naked
      model, appear as promising ways to probe sexual preferences as expressed in
      immersion. Theoretical aspects of VR psychology and further steps in developing a
      sexual preferences assessment method are delineated.

PMID- 11990971
TI  - Analysis of physiological response to two virtual environments: driving and
      flying simulation.
AB  - As virtual reality technology continues to attract significant attention in
      clinical psychology, especially in the treatment of phobias, physiological
      monitoring is increasingly considered as an objective measurement tool for
      studying participants. There are few studies, however, of the normal
      physiological response to virtual environments or reactions to different virtual
      environments. The goal of this study is to analyze nonphobic participants'
      physiological reactions to two virtual environments: driving and flying. Eleven
      nonphobic participants were exposed to each virtual environment for 15 min. Heart
      rate, skin resistance, and skin temperature were measured during physiological
      monitoring, and the Presence and Simulator Sickness Questionnaire scores were
      obtained after each exposure. This study found that skin resistance and heart
      rate variability can be used to show arousal of participants exposed to the
      virtual environment experience and that such measures generally returned to
      normal over time. The data suggest that skin resistance and heart rate can be
      used as objective measures in monitoring the reaction of non-phobic participants
      to virtual environments. We also noted that heart rate variability could be
      useful for assessing the emotional states of participants.

PMID- 11990972
TI  - Emotion and auditory virtual environments: affect-based judgments of music
      reproduced with virtual reverberation times.
AB  - Emotions are experienced both in real and virtual environments (VEs). Most
      research to date have focused on the content that causes emotional reactions, but
      noncontent features of a VE (such as the realism and quality of object rendering)
      may also influence emotional reactions to the mediated object. The present
      research studied how noncontent features (different reverberation times) of an
      auditory VE influenced 76 participants' ratings of emotional reactions and
      expressed emotional qualities of the sounds. The results showed that the two
      emotion dimensions of pleasantness and arousal were systematically affected if
      the same musical piece was rendered with different reverberation times. Overall,
      it was found that high reverberation time was perceived as most unpleasant. Taken
      together, the results suggested that noncontent features of a VE influence
      emotional reactions to mediated objects. Moreover, the study suggests that
      emotional reactions may be a important aspect of the VE experience that can help
      complementing standard presence questionnaires and quality evaluations.

PMID- 11990973
TI  - Sexual harassment in online communications: effects of gender and discourse
      medium.
AB  - Differences in the perception of sexual harassment depending on discourse medium
      (traditional classroom setting versus online) and gender were examined via survey
      with 270 undergraduate participants. It was hypothesized that (1) participants
      would differ in their evaluations of similar behaviors when they were described
      as occurring in a traditional classroom setting as opposed to an online
      environment, and (2) males and females would differ in their evaluations of
      online behaviors. Eight potentially harassing acts were examined--including
      sexually explicit pictures, content, jokes, misogyny, the use of nicknames,
      requests for company, sexual favors, and comments about dress. Misogynist
      comments were seen as more harassing online than in traditional settings, as well
      as using nicknames and comments about dress. In a traditional setting, only
      requests for company were seen as more harassing. In terms of gender differences,
      women rated online pictures and jokes as significantly more harassing than men.

PMID- 11990974
TI  - Online chat rooms: virtual spaces of interaction for socially oriented people.
AB  - The internet has opened a new social space for communication. The present work
      studies interpersonal relationships in cyberspace using the chat channel as an
      interaction medium. Data obtained have outlined the sociodemographic and
      personality profile of internet users who engage in online chats as well as group
      self-perception, chatters' use habits, motivations to interact online, and the
      chatters' network of virtual and face-to-face relationships. Results suggests
      that relationships developed online are healthy and a complement to face-to-face
      relationships. These data are confirmed by personality studies. The theoretical
      and methodological implications of data are discussed.

PMID- 11990975
TI  - Confirmatory factor analysis of internet use and addiction.
AB  - The ever-changing nature of the Internet continues to fuel questions as to its
      benefits and possible drawbacks. One issue that is particularly problematic is
      the validity of claims that the Internet is addictive. The present study used a
      confirmatory factor analysis (CFA) on a data set of 527 participants using the
      same survey developed by Pratarelli et al. (1) We propose a theoretical model of
      the relationship between (1) Internet addiction, (2) a sexual factor, and (3) an
      Internet use factor. These three factors were tested using two structural
      equation models generated on LISREL. The CFA revealed that the three factors are
      not orthogonal to each other, but instead are related to some degree as one would
      expect if a supposed Internet addicted individual exhibited behaviors related to
      each factor. We next tested whether the addiction was the causal factor leaving
      the sex and User factors as endogenous (i.e., resulting from the addiction). The
      second structural equation tested the contrasting possibility that sex and User
      related activities were exogenous to the addiction factor (i.e., the addiction
      resulted from these two activities). The analysis revealed that model 1, where
      the addiction is the causal factor behind the sex and User factors, had a
      stronger model fit index. On the basis of these current data it appears that
      Internet addiction may involve an addictive performance profile which in turn
      leads to excessive behaviors that involve (1) use of the Internet for sexual
      purposes and (2) its functional usefulness for a variety of professional and
      personal goals.

PMID- 11990976
TI  - The effect of visual stimulation via the eyeglass display and the perception of
      pain.
AB  - Hospitalization involves anxiety and pain for many people. Unfamiliar hospital
      settings, various diagnostic and therapeutic procedures, and the sight and sounds
      of medical procedures exacerbate pain and anxiety. By blocking off the anxiety
      inducing sights and sounds of the hospital surroundings and creating a pleasant
      environment, an eyeglass display might be able to change the sensation and
      perception of pain. In this randomized, controlled, crossover study, 72 healthy
      university student volunteers were asked to wear a light-weight eyeglass that
      projected a feeling of watching a 52-inch television screen at 6 1/2 feet in
      distance while pain was produced by a modified tourniquet technique. Subjects
      were randomly assigned to participate in a V-session or B-session first, with
      subsequent cross-over. In a V-session, subjects were instructed to wear the
      eyeglass and watch the soundless display of natural scenery during the inflation.
      In a B-session, the eyeglass that subjects wore would project a static blank
      screen. During V-sessions, there was a significant increase in pain threshold (p
      < 0.001) and pain tolerance (p < 0.001). The degree of immersion was positively
      correlated with improvement in pain threshold, whereas the anxiety level was
      negatively correlated with improvement in pain threshold. These findings have
      implications for using visual stimulation as a positive adjunct to other methods
      of pain relief and for different pain conditions. This study was considered to be
      the pioneer use of visual stimulation in the local Chinese community as an
      adjunct to pain relief.

PMID- 11990977
TI  - Physiological monitoring as an objective tool in virtual reality therapy.
AB  - The goals of this study were twofold: (1) to investigate nonphobics' and phobics'
      physiological response in virtual environments, and (2) to analyze the trend of
      phobics' physiology during virtual reality (VR) treatment. As a measure of
      physiology, heart rate, skin resistance, and skin temperature were acquired. The
      data for two groups of participants were analyzed: 22 nonphobic participants
      (mean = 32 +/- 9.4 years) and 36 subjects with fear of flying (mean = 40 +/- 12.1
      years) who met the DSM-IV criteria for fear of flying. As a result, skin
      resistance showed significant differences between nonphobics and phobics, T(56) =
      2.978 and p < 0.01, respectively. The physiological response of 33 phobic
      participants, who were able to fly without medicine after VR treatment, showed a
      gradual trend toward the nonphobics' physiological responses as therapy sessions
      progressed. In this study, physiological monitoring, in particular skin
      resistance, appeared to be useful both in understanding the physiological state
      of phobic individuals and in evaluating the results of treatment in VR
      psychotherapy.

PMID- 11990978
TI  - Binge drinking and the college environment.

PMID- 11990979
TI  - Trends in college binge drinking during a period of increased prevention efforts.
      Findings from 4 Harvard School of Public Health College Alcohol Study surveys:
      1993-2001.
AB  - The 2001 Harvard School of Public Health College Alcohol Study surveyed students
      at 119 4-year colleges that participated in the 1993, 1997, and 1999 studies.
      Responses in the 4 survey years were compared to determine trends in heavy
      alcohol use, alcohol-related problems, and encounters with college and community
      prevention efforts. In 2001, approximately 2 in 5 (44.4%) college students
      reported binge drinking, a rate almost identical to rates in the previous 3
      surveys. Very little change in overall binge drinking occurred at the individual
      college level. The percentages of abstainers and frequent binge drinkers
      increased, a polarization of drinking behavior first noted in 1997. A sharp rise
      in frequent binge drinking was noted among students attending all-women's
      colleges. Other significant changes included increases in immoderate drinking and
      harm among drinkers. More students lived in substance-free housing and
      encountered college educational efforts and sanctions resulting from their
      alcohol use.

PMID- 11990980
TI  - Underage college students' drinking behavior, access to alcohol, and the
      influence of deterrence policies. Findings from the Harvard School of Public
      Health College Alcohol Study.
AB  - Underage drinking is a major problem at American colleges, but little is known
      about the extent of alcohol use in different student groups, in different
      colleges, and in states with different control policies. We used data from the
      2001 and 3 previous Harvard School of Public Health College Alcohol Studies that
      compared responses of underage students with those of their 21-23-year-old peers.
      Underage students drank alcohol less frequently but were more likely to drink to
      excess when they drank. College educational efforts and deterrent policies were
      limited in their outreach, and half of underage students obtained alcohol very
      easily. Underage students in states with extensive laws restricting underage and
      high-volume drinking were less likely to drink and to binge drink. A majority of
      underage students supported increasing efforts to control underage drinking. The
      results suggest that additional policy efforts to control underage drinking may
      be effective and feasible.

PMID- 11990981
TI  - Prevention efforts underlying decreases in binge drinking at institutions of
      higher education.
AB  - Analyses of 94 Fund for the Improvement of Post-Secondary Education (FIPSE)
      sponsored drug-prevention programs and their outcomes used the Core Survey to
      identify 34 institutions where college students' binge drinking increased (M =
      5.44%) and 60 institutions where it decreased (M = -4.59%) during 2 years of
      program operation. The authors used an inductively derived taxonomy of prevention
      program elements, student variables, student substance use, use-related
      variables, and institutional variables to compare the 2 groups of institutions.
      Only prevention program elements discriminated between groups. Factor analysis of
      discriminating elements identified 8 prevention factors that improved base-rate
      prediction of institutional decrease in binge drinking by 28.1%. Factor synthesis
      yielded a 3-construct binge-drinking prevention model based on student
      participation and involvement strategies, educational and informational
      processes, and campus regulatory and physical change efforts. This model improved
      base-rate prediction of decreased binge drinking by 33.2%.

PMID- 11990982
TI  - Are college students alcoholics?

PMID- 11990983
TI  - Luminol-type chemiluminescence derivatization reagents for liquid chromatography
      and capillary electrophoresis.
AB  - The present paper provides the principles for chemiluminescence of luminol-type
      compounds and their wide and powerful application to the detection system in
      liquid chromatography and capillary electrophoresis as derivatization reagents.
      The reagents can be classified into two types, chemiluminescence labeling and
      chemiluminogenic reagents. The former reagents are highly chemiluminescent
      themselves and used for tagging their intense chemiluminophores to analytes,
      whereas the latter are weakly chemiluminescent but generate intense
      chemiluminescence by reaction with analytes. The liquid chromatographic methods
      utilizing chemiluminescence derivatizing reactions with luminol-type reagents
      allow the analytes to be detected at pmol-sub-fmol levels. Furthermore, the
      chemiluminogenic reactions show high selectivity owing to their selective
      reaction against the analytes permitting facile and reproducible detection.

PMID- 11990984
TI  - Study of the degradation of gelatin in paper upon aging using aqueous size
      exclusion chromatography.
AB  - We studied the aging behaviour of gelatin used to size paper. Thus far, research
      on the aging of paper has largely ignored the sizing agent. Degradation of the
      protein was characterised and the impact of paper components, such as cellulose,
      and aluminium potassium sulphate was evaluated. Whatman No. 1 filter papers sized
      with two types of gelatins (A and B) were prepared as model samples. Commercially
      sized modern papers (Arches) were also studied in order to compare laboratory
      samples with real artist papers. Both types of papers were artificially aged (80
      degrees C, 50% relative humidity for 35 and 94 days). Historic papers were
      included in the study in order to compare artificially aged with naturally aged
      gelatin. The aqueous extracts from the papers were characterised by aqueous size
      exclusion chromatography (SEC) using four PL-Aquagel-OH columns and UV photodiode
      array detection at 220, 254 and 280 nm. Results showed that gelatin undergoes
      hydrolysis upon aging, type A gelatin showing a faster degradation rate than type
      B. The result was an increase in the lower-molar-mass fractions, under 50,000 g
      mol(-1), and especially in a characteristic fraction with a peak molecular mass
      (MP) of 14,000 g mol(-1). A significant decrease in the extraction yields of
      alpha-, beta- and gamma-chains occurred after aging. This was attributed to
      crosslinking, leading to the formation of less-soluble polypeptides with very
      high molar mass (>800,000 g mol(-1)) Less than 10% alum had no impact on the
      degradation rate; higher alum contents accelerated hydrolysis reactions.

PMID- 11990985
TI  - Improved method for direct high-performance liquid chromatography assay of
      angiotensin-converting enzyme-catalyzed reactions.
AB  - A rapid and sensitive assay was developed for determination of the activity of
      angiotensin-converting enzyme (ACE) in the presence of inhibitory peptides
      present in soybean protein hydrolysates. The method utilizes reversed-phase high
      performance liquid chromatography (HPLC) to separate and quantify hippuryl
      histidyl-leucine (HHL) and hippuric acid (HA). HHL and HA were separated on a
      Symmetry C18 column by gradient elution that used mixtures of trifluoroacetic
      acid TFA)-acetonitrile and TFA-water as solvents. Analytical time and baseline
      separation of HA from HHL were improved over previous HPLC methods. In comparison
      to the standard spectrophotometric method, the new HPLC method obviates the need
      for ethyl acetate extraction of HA but requires direct injection of the ACE
      reaction mixture onto the HPLC column.

PMID- 11990986
TI  - Purification of a bacterial pullulanase on a fluidized bed of calcium alginate
      beads.
AB  - Pullulanase from Bacillus acidopullulyticus was purified on a packed bed and a
      fluidized bed of calcium alginate beads. The binding of enzyme activity to the
      medium was found to follow Langmuir isotherm pattern. The maximum binding
      capacity was 1476 U ml(-1) matrix and the dissociation constant was 142 U ml(-1).
      The dynamic binding capacities at 5% breakthrough in the packed and fluidized
      beds were 472 U ml(-1) and 644 U ml(-1), respectively. In the packed bed as well
      as the fluidized bed, an activity recovery of more than 95% with fold
      purification in the range of 46-59 was observed. The elution with a competitive
      inhibitor, viz. maltose, and high-fold purification indicate an affinity-based
      process. The purification process worked equally well with columns of bed volumes
      of 3.8 and 10 ml.

PMID- 11990987
TI  - Liquid chromatography with electrospray ion trap mass spectrometry for the
      determination of five azaspiracids in shellfish.
AB  - Azaspiracid poisoning (AZP) is a new human toxic syndrome that is caused by the
      consumption of shellfish that have been feeding on harmful marine microalgae. A
      liquid chromatography-mass spectrometry (LC-MS) method has been developed for the
      determination of the three most prevalent toxins, azaspiracid (AZA1), 8
      methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3) as well as the
      isomeric hydroxylated analogues, AZA4 and AZA5. Separation of five azaspiracids
      was achieved on a C18 column (Luna-2, 150 x 2 mm, 5 microm) with isocratic
      elution using acetonitrile-water containing trifluoroacetic acid and ammonium
      acetate as eluent modifiers. Using an electrospray ionisation (ESI) source with
      an ion-trap mass spectrometer, the spectra showed the protonated molecules,
      [M+H]+, with most major product ions due to the sequential loss of two water
      molecules. A characteristic fragmentation pathway that was observed in each
      azaspiracid was due to the cleavage of the A-ring at C9-C10 for each toxin. It
      was possible to select unique ion combinations to distinguish between the
      isomeric azaspiracids, AZA4 and AZA5. Highly sensitive LC-MS3 analytical methods
      were compared and the detection limits were 5-40 pg on-column. Linear
      calibrations were obtained for AZA1 in shellfish in the range 0.05-1.00 microg/ml
      (r2 = 0.9974) and good reproducibility was observed with a relative standard
      deviation (%RSD) of 1.8 for 0.9 microg AZAI/ml (n=5). The %RSD values for the
      minor toxins, AZA4 and AZA5, using LC-MS3 (A-ring fragmentation) were 12.3 and
      8.1 (0.02 microg/ml; n=7), respectively. The selectivity of toxin determination
      was enhanced using LC-MS-MS with high energy WideBand activation.

PMID- 11990988
TI  - Packed capillary liquid chromatography-electrospray mass spectrometry of snow
      contaminated with sarin.
AB  - Packed capillary liquid chromatography-electrospray mass spectrometry (LC-ESI-MS)
      was used for the analysis of a snow sample that was accidentally contaminated
      with an organophosphorus chemical warfare agent during the destruction of a
      chemical munition. Sarin, its hydrolysis products and a number of related
      compounds were identified on the basis of acquired LC-ESI-MS data. Full mass
      spectra were acquired for 14 compounds, with all exhibiting MH+, [MH+ACN]+ ions
      and/or protonated dimers that could be used to confirm molecular mass. Sampling
      cone voltages from 20 to 70 V were utilized with the higher sampling voltages
      enhancing formation of structurally important product ions in the ESI interface.
      All data were acquired with a time-of-flight mass spectrometer with a resolution
      of 5,000 (50% valley definition), a resolution that aided in the assignment of
      elemental composition of the observed ions. The application of LC-ESI-MS to snow
      analysis appears to be an attractive alternative to the GC-MS methods, since both
      chemical warfare agents and their hydrolysis products may be analysed directly,
      eliminating the need for additional sample handling and derivatization steps.

PMID- 11990989
TI  - Determination of herbicides and metabolites by solid-phase extraction and liquid
      chromatography evaluation of pollution due to herbicides in surface and
      groundwaters.
AB  - A procedure based on solid-phase extraction (SPE) has been developed for the
      simultaneous preconcentration of three widely used herbicides and seven of their
      most common degradation products. The compounds studied were atrazine and its
      metabolites, desethylatrazine, desethyldesisopropylatrazine (DEDIA), 2
      hydroxyatrazine, desethyl-2-hydroxyatrazine and desisopropyl-2-hydroxyatrazine
      (DIHA), terbutryne and its metabolite 2-hydroxyterbutylazine, and chlorotoluron
      and its metabolite 3-chloro-4-methylphenylurea. A HPLC system with diode array
      detection was used for the separation, identification and quantification of all
      these analytes. In the SPE preconcentration step, different types of sorbent were
      studied: C18 on silica and polymeric sorbents (Oasis and LiChrolut EN), the best
      results being obtained with the styrene-divinylbenzene cartridge and when the
      elution was performed with methanol and ethyl acetate. The detection limits
      obtained were between 0.1 microg l(-1) for DIHA and DEDIA and 0.02 microg l(-1)
      for the other analytes. The method used permitted the determination of these
      herbicides in drinking water at the concentration levels demanded by current
      legislation. The proposed method was used to evaluate the presence and evolution
      with time of these herbicides and their degradation products in samples of
      surface and ground waters from agricultural zones of the provinces of Salamanca
      and Zamora (basins of the Rivers Guarefia and Almar), Spain.

PMID- 11990990
TI  - Determination of nonylphenol ethoxylates in the aquatic environment by normal
      phase liquid chromatography-electrospray mass spectrometry.
AB  - A comprehensive analytical method based on normal-phase liquid chromatography
      electrospray ionization mass spectrometry (NPLC-ESI-MS) has been established for
      determination of nonylphenol ethoxylates (NPEOs) in the aquatic environment.
      Extraction and cleanup of samples were performed on graphitized carbon black
      (GCB) solid-phase extraction cartridges. Complete separation between each
      individual NPEOs was achieved by combining a C18 pre-column with a silica
      analytical column and using acetonitrile-water as eluent. Quantitative
      determination by LC-ESI-MS was achieved in the positive ionization (PI) mode at a
      ramped cone voltage for NPEOs using selected ion monitoring. Recoveries for NPEOs
      ranged between 91.9 and 117.5%, and the limits of detection varied between 0.5
      and 2 ng/l for individual NPEOs with n longer than 2, and between 5 and 0.5
      microg/l for NPIEO and NP2EO. This method was successfully applied to the
      investigation of residual NPEOs with n>2 in the Chongqing area of the Changjiang
      river. NPEOs with n ranging from 1 to 22 were found to vary between 0.1 and 2900
      ng/l with a distribution depending on the depth of water.

PMID- 11990991
TI  - Hyperlayer separation in hollow fiber flow field-flow fractionation: effect of
      membrane materials on resolution and selectivity.
AB  - Hollow fiber flow FFF (HF FlFFF) has recently shown its capability to separate
      and characterize the size of submicrometer particles and has demonstrated the
      potential to be developed into a disposable flow FFF channel. In this work, HF
      FIFFF was used for the hyperlayer separation of micron-sized particles and the
      separation capability was examined by using various hollow fiber membrane
      materials (Polysulfones, cPVC, and PAN). From the experiments, PAN
      (polyacrylonitriles) showed an outstanding performance in particle separation
      compared to the other membranes. By orienting the fiber module in an upright
      direction, the upstream flow migration reduced band broadening of eluted peaks.
      When the efficiency of the PAN hollow fiber system was tested by varying the
      ratio of outflow-rate to radial flow-rate, it was found that optimum separation
      in hyperlayer HF FlFFF can be obtained at the ratio of about 6-7. From the
      examination of retention at or around steric inversion diameter, it was observed
      that experiments showed a good agreement with predictions by semi-empirical
      calculation. In hyperlayer HF FlFFF the diameter based selectivity values were
      shown to be 1.2-1.7 depending on the type of membranes and the field strength
      (the radial flow-rate) conditions.

PMID- 11990992
TI  - Prediction of relative response factors for flame ionization and photoionization
      detection using self-training artificial neural networks.
AB  - The relative response factors (RRFs) of a flame ionization detection (FID) system
      and two pulsed discharge photoionization detection (PID) systems with different
      discharge gases are predicted for a set of organic compounds containing various
      functional groups. As a first step, numerical descriptors were calculated based
      on the molecular structures of compounds. Then, multiple linear regression (MLR)
      was employed to find informative subsets of descriptors that can predict the RRFs
      of these compounds. The selected MLR model for the FID system includes seven
      descriptors and two selected MLR models for the PID systems with argon- and
      krypton-doped helium as the discharge gases, respectively, include six and five
      descriptors. The descriptors appearing in the MLR models were considered as
      inputs for the self-training artificial neural networks (STANNs). A 7-7-1 STANN
      was generated for prediction of RRFs of the FID system, and two STANNs with the
      topologies of 6-7-1 and 5-6-1 were generated for the two PID systems. Comparison
      of the results indicates the superiority of neural networks over that of the MLR
      method. This is due to the nonlinear behaviors of relative response factors for
      all type of detectors studied in this work.

PMID- 11990993
TI  - Identification of non-cross-linked compounds in methanolic extracts of cured and
      aged linseed oil-based paint films using gas chromatography-mass spectrometry.
AB  - Methanolic extracts of paint samples of different composition and age were
      qualitatively investigated by GC-MS using an on-column injector after off-line
      methylation or trimethylsilyl derivatisation, and on-line thermally assisted
      (trans)methylation with tetramethylammonium hydroxide using Curie-point pyrolysis
      GC-MS. The combination of these three analytical strategies led to the
      identification of typical oxidation products of unsaturated fatty acids by
      interpretation of their mass spectrum. Some of the identified compounds have not
      been reported before. Both the off-line and on-line GC-MS strategy show series of
      short-chain fatty (di)acids and C16 and (oxidised) C18 fatty acids. The major
      advantage of the on-line pyrolysis-GC-MS approach is that chemical work-up is
      minimal and very quick. With this technique both the carboxylic acid
      functionalities, and hydroxyl groups are methylated. Young paint films are shown
      to contain relatively more oxidised C18 fatty acids and less diacids compared to
      older paints, which is indicative for the on-going oxidation processes within the
      paint. After trimethylsilylation, monoacylglycerols are detected indicative for
      hydrolytic processes, which reflect the relative distribution of the most
      prominent silylated fatty acids present. Relatively more C16 and C18
      monoacylglycerols are found in young paints, whereas older paints contain higher
      amounts of monoacylglycerols of diacids.

PMID- 11990994
TI  - Fast and efficient separation of cytokinins from auxin and abscisic acid and
      their purification using mixed-mode solid-phase extraction .
AB  - A method for separation of cytokinins from auxin and abscisic acid, which allows
      further separation of cytokinin ribotides from cytokinin bases, ribosides and
      glucosides and their purification on a single Oasis MCX column was developed. Due
      to the mixed reversed-phase and cation-exchange mode of the Oasis MCX sorbent the
      cationic cytokinin bases, ribosides and glucosides as well as the anionic auxin,
      abscisic acid and cytokinin ribotides are retained and can be sequentially eluted
      by solvents containing different concentrations of methanol and ammonium
      hydroxide. Characteristics of the method are high recoveries of analyzed
      phytohormones and their sufficient purity for quantification by HPLC-ELISA (RIA)
      or HPLC-MS.

PMID- 11990995
TI  - Trace level determination of organochlorine, organophosphorus and pyrethroid
      pesticides in lanolin using gel permeation chromatography followed by dual gas
      chromatography and gas chromatography-negative chemical ionization mass
      spectrometric confirmation.
AB  - A methodology for multi-class pesticide determination at trace level in lanolin
      is presented. Gel permeation chromatography on a Bio-Beads SX-3 column followed
      by a dual GC chromatographic determination has been developed. The effluent of
      the analytical column (50% diphenyl-methyl- or 14% cyanopropyl
      phenylpolysiloxane) was split into an electron-capture and a nitrogen-phosphorus
      detection system. The chromatographic system was optimised for 28 pesticides
      commonly used to control sheep pests and corresponding to organochlorine,
      organophosphorus and pyretroid classes. Identification has been carried out by
      gas chromatography coupled to negative chemical ionization mass spectrometry.
      Recoveries ranged from 72 to 94% and the detection limits from 20 to 97 ng/g
      depending on the pesticide class, the RSDs were below 10%. Finally, the developed
      analytical methodology has been successfully applied to the determination of
      pesticides in several lanolin samples.

PMID- 11990996
TI  - Fingerprinting of natural organic matter by capillary zone electrophoresis using
      organic modifiers and pattern recognition analysis.
AB  - Capillary zone electrophoresis was used for characterising nine samples of
      natural organic matter (NOM) using phosphate buffer (25 mM, pH 7) and various
      modifiers; methanol (50 mM), acetonitrile (10%,v/v), dimethyl sulfoxide (5%,v/v),
      and urea (5 M). Principal component analysis (PCA) was used to examine whether
      the electrophoretic profiles can be utilised as fingerprints for tracing the NOM
      samples to their source and/or type of location. It was found that all modifiers
      except methanol affect the electropherograms. Furthermore, it was found that the
      PCA analysis carried out on the electrophoretic profiles recorded in buffer
      solution modified by urea gave the best results for fingerprinting. The
      distribution of the fingerprints suggests a model for the humic substances in
      which all samples can be regarded as mixtures between two endmembers:
      autochtonous and allocthoneous NOM.

PMID- 11990997
TI  - Depth of penetration of binaphthyl derivatives into the micellar core of sodium
      undecenoyl leucyl-leucinate surfactants.
AB  - Two different diastereomeric forms of sodium N-undecanoyl leucyl-leucinate (SULL)
      (both L,L and L,D) are used to examine the role of depth of penetration of chiral
      analytes into the micellar core of polymeric and monomeric surfactants on
      enantioselectivity. In this study, chiral separation of three binaphthyl
      derivatives, i.e. (+/-)-1,1'-bi-naphthyl-2,2'-diamine (BNA), (+/-)-1,1'-bi-2
      naphthol (BOH), and (+/-)-1,1'-binaphthyl-2,2'-dihydrogen phosphate (BNP), are
      studied. Chromatographic results suggest that BNP interacts approximately the
      same with both the C- and N-terminal amino acid of poly SULL, while the
      preferential site of interaction of this analyte with the monomeric form of SULL
      (mono SULL) is at the C-terminal amino acid. This indicates that BNP enantiomers
      penetrate deeper into the micellar core of the poly SULL than that of the mono
      SULL. Varying the temperature resulted in a change in the depth of penetration of
      BNP into the micellar core of the poly SULL. However, the enantiomers of BNA and
      BOH always interact preferentially with the N-terminal amino acid of SULL
      surfactants (both polymer and monomer), independent of the temperatures studied.

PMID- 11990998
TI  - Comparison of micellar and microemulsion electrokinetic chromatography for the
      analysis of water- and fat-soluble vitamins.
AB  - Separation and determination of water- and fat-soluble vitamins by micellar
      (MEKC) and microemulsion electrokinetic chromatography (MEEKC) are compared. MEKC
      is only useful in the quantitative analysis of water-soluble vitamins when sodium
      dodecylsulfate (SDS) is used as the surfactant. However, the separation of
      mixtures containing water- and fat-soluble vitamins is only achieved by MEEKC
      using a microemulsion prepared by mixing SDS as the surfactant, butanol as the co
      surfactant, octane as the non-polar modifier and propanol as the second co
      surfactant. The injection time and the solvent used for the dilution of samples
      have a significant effect on the analysis of lypophilic compounds. The most
      reproducible results in the analysis of fat-soluble vitamins are obtained by
      using the same microemulsion electrolyte as the solvent for samples and an
      injection time of 10 s.

PMID- 11990999
TI  - Analysis of dimeric cyanine-nucleic acid dyes by capillary zone electrophoresis
      in N,N-dimethylacetamide as non-aqueous organic solvent.
AB  - A method based on capillary zone electrophoresis is presented for the
      determination of the purity of commercial dimeric cyanine dyes (TOTO, YOYO, BOBO,
      all -1 and -3 species, LOLO-1, POPO-1) that are common as fluorescent probes for
      nucleic acid staining. These dyes are tetracharged cations, and have a strong
      tendency to interact with negatively charged centres, where they are rapidly
      adsorbed, especially from aqueous solutions. Thus anionic sites at the capillary
      wall must be avoided, and aqueous buffers are not suitable. The method introduced
      here avoids both complications, using non-aqueous N,N-dimethylacetamide as
      solvent, and suppressing the dissociation of silanol groups at the capillary
      surface due to selection of acidic separation conditions (20 mmol/l perchloric
      acid as background electrolyte). The present method enables the determination of
      the purity of all 10 dyes in less than 15 min. The selectivity of the method
      allows separation of at least five main and differentiating a number of
      unresolved minor contaminants as demonstrated in detail for TOTO-3 as an example.
      Quantitation (with 100% normalisation of the peak areas) of nine lots of this dye
      results in a purity between 33 and 87%.

PMID- 11991000
TI  - Simultaneous separation of the enantiomers of cizolirtine and its degradation
      products by capillary electrophoresis.
AB  - The simultaneous enantioselective separation of (+/-)-cizolirtine and its
      impurities: (+/-)-N-desmethylcizolirtine, (+/-)-cizolirtine-N-oxide and (+/- )-5
      (alpha-hydroxybenzyl)-1-methylpyrazole was investigated by capillary
      electrophoresis. Electrokinetic chromatography with carboxymethyl-beta-CD (CM
      beta-CD) and sulfobutyl-ether-beta-CD was tried, showing good enantioseparation
      but poor chemical selectivity. The four racemic pairs were baseline separated, in
      a single run, by cyclodextrin-modified micellar electrokinetic chromatography.
      The migration buffer composition was: (60 mM hydroxypropyl-beta-cyclodextrin-150
      mM sodium dodecyl sulfate-50 mM disodium tetraborate, pH 9.2, in water)-butanol
      95:5, v/v). Work was done to determine the effect of buffer components and their
      optimal concentration on selectivity. The method was validated with respect to
      enantioselectivity of cizolirtine as well as its degradation products and
      separation selectivity between the different components. Linearity, limit of
      detection, limit of quantitation and precision were also determined. This method
      is suitable for the enantiomeric purity determination and stability control of
      cizolirtine (racemic mixture or enantiomers) and its degradation products.
      Examples of electropherograms of (R)-cizolirtine degraded under stressed
      conditions are shown.

PMID- 11991001
TI  - Evaluation of the temporal effect to the peak tailing in flow injection analysis.
AB  - The deformation of a flow injection analysis peak from a Gaussian shape has two
      components: spatial and temporal. The former is mainly attributed to the
      Poisseulie effect in the tubular flow, whereas the latter is related to the
      observing position (of a fixed detector) at which signal is measured. The
      combination of the two makes a skewed peak track on the recorder chart.
      Therefore, an observed peak may imply a substantial fraction of a "false" tail
      due to the effect of non-simultaneous detection. An expanding-Gaussian model is
      proposed to simulate the purely temporal effect, and the asymmetric factors were
      compared with that of the experimental peak shapes. In most cases the peak
      deformation occurring in flow injection analysis should be regarded as
      "temporal". The contribution of the spatial effects (Poisseulie profile and
      others) might not be as significant as it was thought previously.

PMID- 11991002
TI  - Supercoiled circular DNA and protein retention in non-equilibrium chromatography
      temperature and velocity dependence: testimony of a transition.
AB  - Non-equilibrium chromatography (NEC) is a chromatographic mode for the rapid
      separation of polymers. The retention behavior of various proteins (human,
      chicken, bovine serum albumin) and supercoiled circular double-stranded DNA
      (plasmids) was investigated using a phosphate buffer as a mobile phase at
      different velocities and column temperatures with a C1 column with very low
      packing particle diameter as a stationary phase. It was shown that the two
      factors (temperature and velocity) constituted important parameters in the
      retention mechanism of plasmids and proteins in NEC. The protein was retained
      more than the plasmid. At all the temperatures (5, 10, 15, 20, 25 degrees C) the
      plasmid retention increased over the entire flow-rate range (0.02-1.8 ml/min).
      For the protein, the retention curve presented a decrease in the relative
      retention time until a critical value of the mobile phase flow-rate, followed by
      an increase. The transition between the two well known NEC methods, slalom
      chromatography and hydrodynamic chromatography was clearly visualized for
      proteins at the lowest temperature, but did not appear for plasmids due to their
      strong compact structure.

PMID- 11991003
TI  - High-performance liquid chromatographic determination of phenylureas by
      photochemically-induced fluorescence detection.
AB  - A HPLC method, using photochemically-induced fluorescence detection, is described
      for the separation and determination of four phenylurea herbicides including
      diuron, isoproturon, linuron and neburon. A post-column photoreactor, consisting
      of a reactor knitted around a 4 W xenon lamp, has been included between the
      column and the detector, in order to transform the non-fluorescent herbicides
      into fluorophors. The influence of mobile phase composition, flow-rate, pH, and
      buffer concentration has been studied. An acetonitrile-buffer solution of
      potassium phosphate dibasic of pH 7 and 0.01 M concentration (60:40, v/v), was
      selected as optimum. For the fluorimetric detection, optimal excitation/emission
      wavelengths 324/403, 301/433, 335/411 and 326/385 nm were selected for the
      determination of diuron, isoproturon, linuron and neburon, respectively. The
      detection limits ranged between 0.07 and 0.46 microg/ml, according to the
      compound.

PMID- 11991004
TI  - Electrophoretic behaviour of pharmacologically active alkylxanthines.
AB  - The electrophoretic behaviour of ionizable and neutral alkylxanthines commonly
      used in pharmaceutical preparations was studied. The performance of various
      separation modes including capillary zone electrophoresis (CZE), cyclodextrin
      electrokinetic chromatography, and micellar electrokinetic chromatography (MEKC)
      with either sodium dodecyl sulfate (SDS) or bile salts as surfactants, was
      assessed. CZE in an alkaline medium successfully separates ionizable xanthines
      and dyphylline. The addition of carboxymethyl-beta-cyclodextrin to the background
      electrolyte allows only partial resolution of neutral xanthines. Based on MEKC
      results, bile salts exhibit more discrimination ability than SDS to separate
      similar xanthines. The best results are provided by taurodeoxycholic acid, which
      ensures baseline separation of xanthines.

PMID- 11991005
TI  - Analysis of citrates and benzoates used in poly(vinyl chloride) by supercritical
      fluid extraction and gas chromatography.
AB  - Supercritical fluid extraction (SFE) has been demonstrated to be a useful tool in
      the determination of additives in polymeric materials. This paper describes the
      determination of some citrates and benzoates in poly(vinyl chloride) blended with
      33-34% of plasticizer using off-line SFE followed by gas chromatography.
      Experimental factors affecting SFE have been studied by gravimetric analysis,
      followed by analysis of the extracts using a gas chromatograph equipped with a
      flame ionization detector. The extraction process is governed by the solubility
      of the plasticizers in the supercritical fluid or by their diffusion through the
      polymer matrix, which depend on the pressure and temperature used. Maximum
      extraction (>99%) is obtained at pressures and temperatures higher than 40 MPa
      and 80 degrees C, respectively. Due to purge losses, the collection efficiency of
      plasticizers into a liquid solvent ranges from 85 to 90%. The applicability of
      the SFE method is demonstrated using real samples and comparing the results with
      those obtained by conventional Soxhlet extraction.

PMID- 11991006
TI  - Experimental studies of pressure/temperature dependence of protein adsorption
      equilibrium in reversed-phase high-performance liquid chromatography.
AB  - The effect of the average pressure and temperature of the column on the
      adsorption equilibrium of insulin variants on a C8 bonded silica was studied in
      isocratic reversed-phase HPLC. Analytical injections of samples of four different
      insulins (bovine, porcine. Lys-Pro and human recombinant) were carried out at
      constant flow-rate but under increased average pressure. The temperature
      dependence of the retention parameters over the range 25-50 degrees C was studied
      under two different average column pressures (47 and 147 bar). Substantial
      increases of the retention time (up to 300%) were observed when the pressure
      and/or the temperature were increased. Similar adsorption-induced changes in the
      partial molar volume at constant temperature (deltaVm approximately 102 ml/mol)
      were found for all the variants studied. Furthermore, deltaVm was revealed to be
      practically independent of the temperature, which suggests that the temperature
      has no or very little influence on the mechanism of the pressure induced
      perturbations in the molecular structure of the solute. This conclusion was also
      derived from the observed temperature dependence of the logarithm of the
      retention factor (k) measured under different pressures. The relation between the
      temperature and In k was nonlinear with a parabolic shape. Moreover, the shapes
      of the plots corresponding to the low and high pressures were found to be exactly
      the same, except that the curves were vertically shifted, due to the difference
      between the two average column pressures. These results indicate that pressure
      and temperature affect the retention behavior of insulins in a different and
      separate way.

PMID- 11991007
TI  - Preparation and application of a new ligand exchange chiral stationary phase for
      the liquid chromatographic resolution of alpha-amino acid enantiomers.
AB  - A new liquid chromatographic ligand exchange CSP has been prepared by covalently
      bonding (S)-N,N-carboxymethyl undecyl leucinol monosodium salt onto silica gel
      and employed in resolving various alpha-amino acids. The new CSP was quite good
      in resolving various a-amino acids and the resolution results were dependent on
      the type and content of organic modifier in the mobile phase. From these results,
      a chiral recognition model using a lipophilic interaction between the tethering
      alkyl group of the CSP and the substituent at the chiral center of alpha-amino
      acids was proposed. The liquid chromatographic resolution of alpha-amino acids on
      the new CSP was also found to be dependent on the Cu(II) concentration in the
      mobile phase and the column temperature.

PMID- 11991008
TI  - Synthesis and chromatographic properties of a novel chiral stationary phase
      derived from heptakis(6-azido-6-deoxy-2,3-di-O-phenylcarbamoylated)-beta
      cyclodextrin immobilized onto amino-functionalized silica gel via multiple urea
      linkages.
AB  - A novel chiral stationary phase (PPHCDN7) was prepared by immobilization of
      heptakis(6-azido-6-deoxy-2,3-di-O-phenylcarbamoylated)-beta-cyclodextrin (PPHCD)
      onto the surface of amino-functionalized silica gel via multiple urea linkages
      derived from an extended application of the Staudinger reaction. A wide range of
      structurally divergent racemic drugs and other compounds were successfully
      separated into their enantiomers under both normal and reversed-phase conditions.
      Beta-adrenergic blockers and racemic tertiary, secondary and primary amines were
      readily separated using a mixture of methanol and aqueous triethylammonium
      acetate buffer. The optimal pH value for the separation falls in the range of
      4.65 to 6.30. With atropine and isoproterenol, good enantioseparations with
      separation factors of alpha>5 were easily attainable.

PMID- 11991009
TI  - Evaluation of high-performance liquid chromatography column retentivity using
      macromolecular probes I.
AB  - The application of macromolecular probes is proposed for evaluation of HPLC
      column retentivity. The idea is tested with a set of different commercial silica
      C18 reversed-phases. For comparison, porous glass C18 and
      polystyrene/divinylbenzene column packings are also included. Polar, mainly
      silanophilic interactions are evaluated. The retention volumes of a series of
      narrow molar mass distribution polystyrenes (PS) and poly(methyl methacrylate)s
      (PMMA) in toluene eluent are compared. Toluene is a weak mobile phase concerning
      silica gel surface and it promotes adsorption of PMMA on silanols, while PS is
      not adsorbed from toluene. Simultaneously, toluene is a thermodynamically good
      solvent for both polymers so that extensive partition in favour of stationary
      phase is not probable. Differences in retention behaviour of PS and PMMA indicate
      presence of abundant free silanols on the surface of some reversed-phases. These
      silanols are accessible even for large macromolecules of PMMA. Pore diameter and
      pore volume of the column packing can be semiquantitatively evaluated from the
      elution data of PS in toluene in the course of retentivity tests.

PMID- 11991010
TI  - Development and optimization of organic acid analysis in tobacco with ion
      chromatography and suppressed conductivity detection.
AB  - With the aid of a central composite face-centered design, an ion chromatographic
      method was developed and optimized for analyzing organic acids in tobacco. A
      Dionex-100 ion chromatograph with an ion suppressor and a conductivity detector,
      and a Bio-Rad Aminex HPX-87H column were employed. Only 13 analyses were required
      to optimize two factors: column temperature and eluent strength. Two sets of
      optimal conditions for separating nine acids were found: 1.8 mM HFBA eluent and
      42 degrees C column temperature, and 0.8 mM HFBA eluent and 50 degrees C column
      temperature. The flow-rate was 0.6 ml min(-1) and the analysis time was 18 min or
      less. A sample preparation procedure included extraction of 2 g ground tobacco
      with 100 ml of 5 mM sulfuric acid solution for 3 h, filtration of the extract,
      and dilution of the filtrate 10-fold with deionized water.

PMID- 11991011
TI  - Molecular recognition through the exact placement of functional groups on non
      covalent molecularly imprinted polymers.
AB  - To investigate the extent of the placement of functional groups in the non
      covalent molecularly imprinted polymers contributing to selectivity, three kinds
      of molecularly imprinted methacrylic acid-ethylene glycol dimethacrylate
      copolymers were prepared at higher polymerization temperature (60 degrees C)
      using 2-L-phenylalanylamino-pyridine, 3-L-phenylalanylamino-pyridine, or 4-L
      phenylalanylamino-pyridine as a template molecule, respectively. The enantiomeric
      recognition performance of these molecularly imprinted polymers (MIPs) in the
      high-performance liquid chromatography (HPLC) mode was investigated. The polymers
      exhibited efficient enantiomeric resolution of the racemic mixture of their
      printing molecules and could hardly resolve the enantiomers of other substrates
      that were structurally analogous to the imprinting molecules, but different from
      spatial interaction sites on the polymer with the methacrylic acid residues. Our
      results showed that the shape and spatial orientation of functionality of
      imprinted binding sites were critical for recognition and the recognition
      properties of MIPs were greatly influenced by the minor difference of N position
      on the pyridine ring and caused by the distance accuracy of functional groups in
      the binding sites. The implication of these findings with respect of the
      mechanism of recognition was discussed.

PMID- 11991012
TI  - Liquid chromatography-mass spectrometry and capillary electrophoresis combined
      approach for separation and characterization of multicomponent peptide mixtures.
      Application to crude products of leuprolide synthesis.
AB  - A sequential combination of reversed-phase liquid chromatography-mass
      spectrometry (LC-MS) and capillary electrophoresis (CE) has been explored in
      order to perform separation and characterization of a multicomponent peptide
      mixture from the synthesis of leuprolide. The mixture was first analyzed and
      fractionated by LC-MS, and the collected fractions were subsequently separated by
      CE. Unambiguous identification of the electrophoretic peaks was achieved by
      injecting the collected fractions separately and spiking the leuprolide crude
      mixture. Furthermore, structural information about the components of the mixture
      provided by several semi-empirical migration models has been used to check the
      accuracy of the structures previously proposed by LC-MS. Combination of the two
      orthogonal techniques results in an enhancement of their individual selectivity
      characteristics.

PMID- 11991013
TI  - Substandard and counterfeit drugs in developing countries.

PMID- 11991014
TI  - The outbreak and control of Ebola viral haemorrhagic fever in a Ugandan medical
      school.
AB  - Uganda has just experienced the largest outbreak of Ebola haemorrhagic fever
      (EHF) ever recorded. Mbarara University Teaching Hospital (MUTH) is responsible
      for training approximately one-third of Uganda's doctors. Mbarara is located in
      SouthWest Uganda, 614 km from Gulu, the main epicentre of the outbreak. On 23
      October a patient was admitted to the medical ward of MUTH with an acute fever.
      He soon exhibited haemorrhagic symptoms and died. He was later confirmed to have
      suffered Ebola. Three more patients subsequently contracted the disease. All
      died. There were no further cases in Mbarara. No members of staff or medical
      student was infected. We give details of the clinical features of those patients
      who contracted the disease, the setting up of an Ebola isolation unit, the case
      surveillance and the search for the source of the outbreak. The implications for
      similar institutions in East Africa are discussed.

PMID- 11991015
TI  - Comparative bioavailability of oral sugar-coated and plain formulation of
      chloroquine phosphate marketed in Tanzania.
AB  - The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight)
      of a sugar-coated (Dawaquin) and a plain formulation (Shellyquine) of chloroquine
      phosphate were compared in two groups of 10 volunteers each, following an
      overnight fast. Whole blood chloroquine concentrations were measured using high
      performance liquid chromatography (HPLC) and bioavailability was determined by
      measuring area under the blood chloroquine concentration curve (AUC ng mL(-1) h)
      and the peak blood chloroquine concentration (Cpmax ng/mL). The AUC and Cpmax for
      Shellyquine were 4396.3 +/- 833 ng mL(-1) h and 162 +/- 14 ng/mL, respectively.
      The AUC and Cpmax for Dawaquin were 2060 +/- 339 ng mL(-1) h and 56.6 +/- 5.2
      ng/mL, respectively. Shellyquine was significantly more bioavailable than
      Dawaquin (P<0.001). Although the Cpmax for Dawaquin was higher than the required
      therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood
      levels may not guarantee a rapid clearance of parasites. The differences between
      the two formulations point to a problem in the quality of pharmaceuticals
      marketed in this country, whose extent need to be ascertained further. Failure of
      chloroquine phosphate in this country has already been declared by the Ministry
      of Health, and the potential contribution of poorly formulated products remains a
      subject of debate.

PMID- 11991016
TI  - A study of patients attending for eye surgery at a rural hospital in the Republic
      of Benin.

PMID- 11991017
TI  - Keep on worrying about meconium.

PMID- 11991018
TI  - Urinary pathogens' resistance to common antibiotics: a retrospective analysis.
AB  - The susceptibility of urinary pathogens to common antibiotics was investigated
      and the results analysed retrospectively using the WHONET computer program. Of
      1776 urine samples (44 catheterized) processed, 510 (28.7%) urinary pathogens
      were isolated. Of these 510 positive cultures, 455 (89.2%) were gram-negative
      bacilli, 45 (8.8%) Candida species and 10 (1.9%) gram-positive cocci. Of the 44
      catheterized samples, 32 (72.7%) yielded significant bacteriuria and these were
      mainly gram-negative bacteria (24/32). The commonest pathogen isolated was
      Escherichia coli (47.3%) followed by Klebsiella species (10.3%), non-fermenters
      other than Pseudomonas species (9%), Candida species (8.8%), Providentia species
      (7%), Pseudomonas species (5.6%), Citrobacter species (3.7%), Enterobacter
      species (3.3%) and Proteus species (2.5%). The isolation of gram-negative
      bacteria among inpatients and outpatients was 71.6% and 28.3%, respectively. The
      critical care unit, nephrourology, obstetric and gynaecology, medical and
      surgical wards were found to be high-risk areas constituting 58.7% of the major
      isolates. The highest and lowest mean resistance among gram-negative bacteria to
      common antibiotics was 93.5% to ampicillin and to 61% gentamicin. The mean
      resistance to norfloxacin, amoxy-clavulanic acid, nitrofurantoin, trimethoprim
      sulfamethoxazole and cefazolin was 65%, 67%, 75.5%, 76% and 77.5%, respectively.
      The most resistant pathogen to common antibiotics was found to be Proteus species
      (resistance 80% and above). Overall susceptibility testing demonstrated decreased
      usefulness of common antibiotics and demonstrates a need for a re-evaluation of
      common antibiotics used in the therapy for urinary tract infection.

PMID- 11991019
TI  - Hypothermia: prevention at community level.

PMID- 11991020
TI  - Echocardiographic features of peripartum cardiac failure: the Zaria syndrome.
AB  - Zaria has the highest incidence of peripartum cardiac failure, a syndrome of
      unsettled aetiology. Over the years it has been noted that there has been a
      decrease in the period of treatment by traditional methods from an average of 90
      days to 30 days and with a complete avoidance of hot bed treatment. Twenty-one
      subjects with the syndrome were studied: they exhibited the same clinical
      findings as evinced in previous reports from our centre. Echocardiography
      findings of dilated heart with depressed left ventricular function were noted.
      There was a statistically significant relationship between the duration of
      practice and ejection fraction (EF), r=0.36 and P<0.05, duration of practice and
      left ventricular internal diameter in diastole (LVIDd), r=0.28, P<0.05. Were
      these subjects suffering from a quiescent heart muscle disease from a previous
      viral myocarditis and did they require an expanded volume as a trigger? Or are
      they intolerant of salt requiring only a small increase from the traditional
      method of treatment to precipitate cardiac failure? Further investigation in the
      field of molecular biology is required.

PMID- 11991021
TI  - Kerosene poisoning in children: a report from northern Jordan.
AB  - A prospective study was conducted over 4 years to evaluate the children with
      kerosene ingestion in northern Jordan. One hundred and twenty children aged 11
      months to 6 years (mean age 2.2) were studied. The majority of patients (90%)
      were below the age of 4. Most of the cases (42%) were seen during the summer
      season. The most common presenting symptoms were: cough (70.6%); tachypnoea
      (59.6%), and fever (55.1%). In 25 patients the parents had induced vomiting
      before arrival. The main sites of storage for kerosene were: under stairs
      (36.7%); the kitchen; (33.3%) and bathroom (11.7%). The main containers used were
      soft drink bottles, water jugs and water glasses. The patients were treated
      symptomatically, and all except one who was comatose on admission made a complete
      recovery. Health education and preventive measures are given.

PMID- 11991022
TI  - HIV testing using dried blood spots.

PMID- 11991023
TI  - Non-prolapsing colostomy in a massively dilated colon.

PMID- 11991024
TI  - Traditional healers and their practices in Malawi.

PMID- 11991025
TI  - Experience with unoperated cleft lip and palate patients in a Nigerian teaching
      hospital.
AB  - A review of 31 cases of unoperated cleft lip and palate patients aged 10 years
      and above managed over a 6 years period at a suburban Nigeria teaching hospital
      is presented. There was an overall preponderance of the female gender and
      isolated cleft lip (58%) was the most predominant. Although clefts were very wide
      on presentation, there was adequate well-developed soft tissue in adults to
      achieve a cosmetically and functionally acceptable repair. This study also
      confirms the views that late primary repair of facial cleft is less likely to
      produce impaired growth of the maxillaas is commonly observed in early repair.
      However, the advantages of early repair cannot be over-emphasized.

PMID- 11991026
TI  - Ectopic pregnancy in a rural population with a high twinning rate.

PMID- 11991027
TI  - The pattern of surgical cancers in Nigeria: the Benin experience.

PMID- 11991028
TI  - Drug prescribing pattern of interns at a government healthcare centre in northern
      India.
AB  - Prescribing habits of interns posted at a primary health centre for a period of 2
      months (January 1994 and February 1994) were studied. Among the 1457
      prescriptions collected, the average number of drugs per prescription was 2.47.
      The commonest groups of drugs prescribed were antibiotics (33.9%), analgesics and
      anti-inflammatories (17.0%), vitamins (13.0%), cough syrups (10.5%) and
      antihistamines (8.6%). The use of injectables was uncommon (0.9%). Most of the
      drugs prescribed were from the local drugs list of the centre (84.2%) consisting
      of 36 drugs. The list contained 20 drugs with proprietary names of which six were
      fixed-dose combinations. The local drug list needs modification. The proportion
      of drugs prescribed by generic name was 49.5%. As per Kunin's criteria, 57.9% of
      the antibiotics used were appropriate. Interns often forget to write the
      diagnosis (43%), signs and symptoms (50.2%), dosages and frequency of treatment.
      The result of this baseline study may be useful in promoting the education
      necessary in order to achieve the objectives of good prescribing.

PMID- 11991029
TI  - Leech infestation: an unusual cause of hoarseness.

PMID- 11991030
TI  - 'Muti' poisoning in Zimbabwe.

PMID- 11991031
TI  - False aneurysms in association with AIDS.

PMID- 11991032
TI  - A unique case of bladder mycetoma.

PMID- 11991033
TI  - Nonoperative management of an intramedullary tuberculoma.

PMID- 11991034
TI  - Leprosy at the cutting edge: 2000 to 2005, and beyond.

PMID- 11991035
TI  - Control of sexually transmitted infections.

PMID- 11991036
TI  - Influence of the quality of obstetric care on the caesarean section rate and
      perinatal mortality.

PMID- 11991037
TI  - Effect of fortification on the specific gravity of human breast milk.

PMID- 11991038
TI  - Honey and sugar as a dressing for wounds and ulcers.

PMID- 11991039
TI  - Club foot.

PMID- 11991040
TI  - Primary cutaneous amyloidosis.

PMID- 11991041
TI  - Diabetes and diet.

PMID- 11991042
TI  - Cholera and breastfeeding.

PMID- 11991043
TI  - The optimal duration of exclusive breastfeeding.

PMID- 11991044
TI  - Should we worry about meconium? A controlled study of neonatal outcome.
AB  - Over a 7 month period 131 cases with intrapartum draining of meconium-stained
      liquor (MSL) were reviewed and the neonatal outcome compared to that of all
      deliveries during the same time. Mean Apgars were significantly lower and the
      proportion of neonates with poor Apgar scores was higher if thick meconium was
      present, but not for thin meconium. Prolonged labour was more common and
      associated with a particularly worse outcome in the MSL group. Caesarean sections
      were performed twice as frequently, failure to progress being the indication in
      more than half the cases. Close monitoring of labour in the presence of MSL
      (particularly thick MSL) is important to detect failure to progress and fetal
      distress early.

PMID- 11991067
TI  - Selective production of organic acids in anaerobic acid reactor by pH control.
AB  - The selective production of organic acids by anaerobic acidogenesis with pH
      control was examined using a chemostat culture. The results showed that the
      product spectrum in the acid reactor strongly depended on the culture pH. Under
      acidic and neutral conditions, the main products were butyric acid, while acetic
      and propionic acids were the main products under the basic condition. This
      phenomenon was reversible between the acidic and basic conditions, and was not
      affected by the dilution rate. The change in the main products was caused by the
      change in the dominant microbial populations, from butyric acid-producing
      bacteria to propionic acid-producing bacteria in the acid reactor due to the pH
      shift. The control of culture pH was considered to be a useful way for
      controlling the product spectrum in the anaerobic acid reactor.

PMID- 11991068
TI  - Effect of synthetic and natural culture media on laccase production by white rot
      fungi.
AB  - Laccase is among the major enzymes of white rot fungi involved in lignocellulose
      degradation. The present paper reports its production by two white rot fungi
      (Coriolus versicolor, Funalia trogii) under different nutritional conditions.
      Various synthetic culture media and natural culture medium (molasses wastewater)
      were tested. Enzyme production in various synthetic culture media, molasses
      wastewater (vinasse) culture medium and in the absence or presence of cotton
      stalk supplements showed that vinasse culture medium was a better laccase-inducer
      medium than the synthetic culture medium. Addition of cotton stalk to various
      media enhanced the enzyme production. The highest laccase activity was obtained
      in vinasse culture medium with cotton stalk.

PMID- 11991069
TI  - Influence of type and concentration of flavinogenic factors on production of
      riboflavin by Eremothecium ashbyii NRRL 1363.
AB  - A study was conducted to determine the effect of various low cost organic wastes
      as flavinogenic factors and the various concentrations at which they induced
      flavinogenecity resulting in higher yields of riboflavin. A high-yielding
      riboflavin strain; Eremothecium ashbyii NRRL 1363 was chosen to determine the
      flavinogenicity. Carbon source at 50 g l(-1) (dextrose equivalents) of molasses
      and nitrogen source at 50 g l(-1) (weight/volume) of peanut seed cake were found
      to be optimal levels to yield higher riboflavin. Among the organic wastes, (beef
      extract, hog casings, blood meal, fish meal) hog casings in association with fish
      meal supported the highest yield of riboflavin. Among the different recovery
      processes studied, a vacuum drying process was the most efficient allowing
      maximum yield, followed by drying at 90 degrees C and freeze-drying. It is
      apparent from this study that inexpensive or waste organic materials could induce
      E. ashbyii to synthesize and secrete riboflavin at higher levels in the medium
      and this could be purified using a vacuum drying process. This bioconversion
      process allows us to recycle the biomaterials and produce a value-added product
      of economic importance.

PMID- 11991070
TI  - Anaerobic decolorisation of simulated textile wastewater containing azo dyes.
AB  - This study deals with the decolorization of the commercially important azo dyes,
      Orange II (C.I. Acid Orange 7) and Reactive Black 3HN (C.I. Reactive Black 8)
      under anaerobic conditions in wastewater. Laboratory scale semicontinuous studies
      were conducted using simulated cotton dyeing wastewater at ambient temperatures
      (24-28 degrees C) by maintaining a HRT of 10 days. The dye concentration in
      wastewater was maintained at 100 mg/l. The reactors were operated for 58 days and
      Orange II and Black 3HN were easily decolorized under the experimental conditions
      employed. The performance of the bioreactors was evaluated by monitoring
      oxidation-reduction potential (ORP) in the reactor, color and Chemical oxygen
      demand (COD) removal. Color removal of >99% was achieved in both the dye
      containing reactors. COD removals of up to 95%, 92% and 94% were achieved in
      control, orange- and black dye-containing reactors, respectively. Effect of dyes
      and salts present in textile wastewater on methanogenesis was evaluated based on
      maximum methane production and methanogenic activity. Based on the maximum
      methane production data, no inhibition of methanogenesis was observed for dye
      concentrations of up to 400 mg/l for both the dyes. However from the methanogenic
      activity data, it was observed that the black dye concentration of 400 mg/l
      seemed to cause inhibition of methanogenesis.

PMID- 11991071
TI  - Low temperature pre-treatment of domestic sewage in an anaerobic hybrid or an
      anaerobic filter reactor.
AB  - The pre-treatment of domestic sewage for removal of suspended solids (SS) at a
      process temperature of 13 degrees C and an hydraulic retention time (HRT) of 4 h
      was investigated in an anaerobic filter (AF) and anaerobic hybrid (AH) reactor.
      The AF and the top of the AH reactor consisted of vertical sheets of reticulated
      polyurethane foam (RPF) with knobs. All biomass in the AF was only in attached
      form to avoid clogging and sludge washout. The AF reactor showed a significantly
      higher removal of total and suspended chemical oxygen demand (COD) than the AH
      reactor, respectively, 55% and 82% in the AF reactor and 34% and 53% in the AH
      reactor. Because the reactors were operated at a short HRT and low temperature,
      the hydrolysis, acidification and methanogenesis based on the influent COD were
      limited to, respectively, 12%, 21% and 23% for the AF reactor and 12%, 17% and
      16% for the AH reactor. The excess sludge from the AH reactor was more stabilised
      and had a better settling capacity and dewaterability. However, the excess sludge
      from both the AH and AF reactors needed stabilisation. Therefore, the AF reactor
      is recommended for the pretreatment of domestic sewage at low temperatures.

PMID- 11991072
TI  - Physico-chemical and chemical properties of some coconut coir dusts for use as a
      peat substitute for containerised ornamental plants.
AB  - Selected physico-chemical and chemical characteristics of 13 coconut coir dust
      (mesocarp pithy tissue plus short-length fibres) samples from Asia, America and
      Africa were evaluated as peat alternatives. All properties studied differed
      significantly between and within sources, and from the control Sphagnum peat. pH
      of coir dust was slightly acidic, whereas salinity varied dramatically between 39
      and 597 mS m(-1) in the saturated media extract. The cation exchange capacity and
      carbon/nitrogen (C/N) ratio ranged from 31.7 to 95.4 cmol(c) kg(-1) and from 75
      to 186, respectively. Most carbon was found as lignin and cellulose. The
      concentrations of available nitrogen, calcium, magnesium and micro-elements were
      low, while those of phosphorus and potassium were remarkably high (0.28-2.81 mol
      m(-3) and 2.97-52.66 mol m(-3) for P and K, respectively). Saline ion
      concentrations, especially chloride and sodium, were also high.

PMID- 11991073
TI  - Removal of cadmium and mercury ions from aqueous solution by sorption on treated
      Pinus pinaster bark: kinetics and isotherms.
AB  - Formaldehyde pretreated Pinus pinaster bark was used to sorb Cd2+ and Hg2+ from
      aqueous solutions. The sorption kinetics showed hyperbolic dependence of the
      proportion of cation adsorbed on time, and the sorption isotherms were
      satisfactorily fitted by Freundlich equations, with k and n values showing Hg2+
      to be more efficiently sorbed than Cd2+. Except for low cation concentrations,
      for which sorption was practically total at all initial pH > or = 6, sorption
      increased in this range, in keeping with a mechanism based on ion exchange with
      the hydroxyl protons of ring B of the procyanidin units of the tannins in the
      bark.

PMID- 11991074
TI  - Isolation of a biodegradable sterol-rich fraction from industrial wastes.
AB  - Several industrial waste materials were screened for their sterol content. The
      possibility of using these industrial by-products as sterol sources for the
      microbiological production of 4-androsten-3,17-dione (AD) and 1,4-androsta-diene
      3,17-dione (ADD) was investigated. Two methods of obtaining the sterol fraction
      from wastes were developed. Sterol-rich (96-98%) fractions were isolated in a
      yield above 70%, from a tall-oil effluent of a paper pulp industry and from
      edible-oil deodorizates. These fractions were subsequently used as a substrate
      for microbial degradation by a Mycobacterium sp. strain and proved to be easily
      converted to AD and ADD.

PMID- 11991075
TI  - Chloride, sodium, potassium and faecal bacteria levels in surface runoff and
      subsurface percolates from grassland plots amended with cattle slurry.
AB  - This study investigated the effectiveness of vegetated buffer strips for removing
      contaminants in runoff from grassed plots (slope 15%) after application of cattle
      slurry. Plots (8 x 8 m2 or 8 x 3 m2) received slurry or inorganic fertilizer, and
      then simulated rainfall (1, 7 and 21 days after slurry/fertilizer application);
      after each event, runoff and percolates were sampled at various distances
      downslope (2, 4, 6, and 8 m), and analysed for Cl-, Na+, K+ and faecal bacteria
      contents. Contaminant concentrations were markedly higher in runoff from the
      slurry-amended plots than in runoff from the fertiliser-amended plots. After the
      first rainfall event, some contaminant concentrations in runoff from the slurry
      amended plots declined with distance downslope (i.e. with buffer strip width),
      supporting the relative efficacy of the strip for retaining pollutants. After the
      second and third rainfall events, by contrast, our results suggest remobilisation
      of contaminants retained during the first event. Faecal bacteria levels
      (especially streptococcus levels) remained high throughout the study, even in
      percolates and runoff collected 8 m downslope after the third rainfall event, and
      indeed even downslope of the adjacent fertilizer-amended plots (indicating
      lateral movement): this suggests that bacterial contamination may be the most
      significant risk arising from slurry application.

PMID- 11991076
TI  - Effect of distillery effluent on seed germination in some vegetable crops.
AB  - A laboratory experiment was conducted to study the effect of different
      concentrations (0%, 5%, 10%, 15%, 20%, 25%, 50%, 75% and 100%) of distillery
      effluent (raw spent wash) on seed germination (%), speed of germination, peak
      value and germination value in some vegetable crops: tomato, chilli, bottle
      gourd, cucumber and onion. The distillery effluent did not show any inhibitory
      effect on seed germination at low concentration except in tomato, but in onion
      the germination was significantly higher (84%) at 10% concentration as against
      63% in the control. Irrespective of the crop species, at highest concentrations
      (75% and 100%), complete failure of germination was observed. The speed of
      germination, peak value and germination value also followed a similar trend. We
      found that a concentration of 5% was critical for seed germination in tomato and
      bottle gourd, and 25% in the rest of the crops. Based on the tolerance to
      distillery effluent, the crops studied have been arranged in the following order:
      cucumber > chilli > onion > bottle gourd > tomato. We conclude that the effect of
      the distillery effluent is crop-specific and due care should be taken before
      using the distillery effluent for pre-sowing irrigation purposes.

PMID- 11991077
TI  - Oyster mushroom cultivation with rice and wheat straw.
AB  - Cultivation of the oyster mushroom, Pleurotus sajor-caju, on rice and wheat straw
      without nutrient supplementation was investigated. The effects of straw size
      reduction method and particle size, spawn inoculation level, and type of
      substrate (rice straw versus wheat straw) on mushroom yield, biological
      efficiency, bioconversion efficiency, and substrate degradation were determined.
      Two size reduction methods, grinding and chopping, were compared. The ground
      straw yielded higher mushroom growth rate and yield than the chopped straw. The
      growth cycles of mushrooms with the ground substrate were five days shorter than
      with the chopped straw for a similar particle size. However, it was found that
      when the straw was ground into particles that were too small, the mushroom yield
      decreased. With the three spawn levels tested (12%, 16% and 18%), the 12% level
      resulted in significantly lower mushroom yield than the other two levels.
      Comparing rice straw with wheat straw, rice straw yielded about 10% more
      mushrooms than wheat straw under the same cultivation conditions. The dry matter
      loss of the substrate after mushroom growth varied from 30.1% to 44.3%. The straw
      fiber remaining after fungal utilization was not as degradable as the original
      straw fiber, indicating that the fungal fermentation did not improve the feed
      value of the straw.

PMID- 11991078
TI  - Biosorption of monovalent and divalent ions on baker's yeast.
AB  - Biosorption of monovalent ions Na+ and K+, by deactivated protonated yeast
      (Saccharomyces cerevisiae) at controlled pH, was compared with biosorption of
      divalent ions Ca2+ and Mg2+ to help to understand the underlying
      bindingmechanisms. The adsorption for monovalent ions was accompanied by H+
      release. Divalent ions were sorbed by proton displacement, and also an additional
      mode not accompanied by release of H+. The sorption uptake of both monovalent and
      divalent metal ions increased with pH in the range 3-7 peaking at 6.75.
      Equilibrium sorption isotherms at pH = 6.75 showed that the totalmaximum
      biosorptive capacity for metal ions decreased in the following order: Ca > Mg >
      Na > or = K.

PMID- 11991079
TI  - Aquacultural and socio-economic aspects of processing carps into some value-added
      products.
AB  - Carps are the mainstay of Indian aquaculture, contributing over 90% to the total
      fish production, which was estimated to be 1.77 million metric tonnes in 1996.
      Carp culture has a great potential for waste utilization and thus for pollution
      abatement. Many wastes such as cow, poultry, pig, duck, goat, and sheep excreta,
      biogas slurry, effluents from different kinds of factories/industries have been
      efficiently used for enhancing the productivity of natural food of carps and
      related species. Besides, several organic wastes/byproducts such as plant
      products, wastes from animal husbandry, and industrial by-products have been used
      as carp feed ingredients to lower the cost of supplementary feeding. However, to
      ensure the continued expansion of fish ponds and the pollution control, there
      must be a market for the fish (carps) produced in these ponds. The carps have,
      however, a low market value due to the presence of intra-muscular bones, which
      reduces their consumer acceptability. Thus, a need was felt to develop some
      boneless convenience products for enhancing the consumer acceptability of the
      carps. Efforts were made to prepare three value-added fish products, namely fish
      patty, fish finger and fish salad from carp flesh and were compared with a
      reference product ('fish pakoura'). Sensory evaluation of these products gave
      highly encouraging results. The methods of preparation of these products were
      transferred to some progressive farmers of the region who prepared and sold these
      products at very attractive prices. Carp processing has a great potential for the
      establishment of a fish ancillary industry and thus for boosting the production
      of these species. In Punjab alone, there is a potential of consuming 32,448
      metric tonnes per annum of such value-added products (which would require 54,080
      metric tonnes of raw fish). The development of value-added products has a
      significant role in raising the socio-economic status of the people associated
      with carp culture. The average cost of production of these products was estimated
      to be INR 80 per kg. With a sale price of INR 110 per kg, and a sale of 50 kg per
      day of the value-added products (26 days a month), the average monthly income of
      a carp-processing unit comes to be INR 39,000 (929 USD, approximately).

PMID- 11991080
TI  - Pilot plant recovery of catheptic proteases from surimi wash water.
AB  - Recovery of bioactive compounds, such as proteolytic enzymes, from waste streams
      is a means to both recuperate value and reduce environmental pollution.
      Previously optimized lab-scale parameters for the recovery of a stable crude
      protease fraction from Pacific whiting (Merluccius productus) surimi wash water
      were tested using pilot plant equipment. Pretreatment of surimi wash water with
      60 degrees C heat, acidification to pH 6, and centrifugation doubled
      ultrafiltration membrane flux and significantly improved protease purity by
      reducing a majority of the 35-205 kDa proteins. Concentrated crude protease
      obtained from wash water contained predominantly cathepsin L activity. Enzyme
      purity was increased about 100-fold, and yield was approximately 80%. Stability
      (frozen and freeze-dried protease) was maintained for 9 weeks at -80 degrees C.
      Freeze-dried preparations were also stable for 9 weeks at 4 and -15 degrees C.
      Successful application of pilot plant conditions allows for sufficient production
      of protease for further investigations into their applicability.

PMID- 11991081
TI  - Fatty acid compositions of seed oils of Haematostaphis barteri and Ximenia
      americana.
AB  - The fatty acid compositions of the seed oils of Haematostaphis barteri (blood
      plum) and Ximenia americana (Wild olive) plants were determined by the Gas
      Chromatography Mass Spectroscopy (GC-MS) technique. H. barteri contained six
      fatty acids with oleic (69.35%) and stearic (15.40%) the most abundant
      unsaturated and saturated fatty acids, respectively. Unsaturated higher fatty
      acids, namely Eicosadienoic (6.92%) and Erucic acid (2.74%) were detected and the
      total unsaturation for the oil was 79.01%. For X. americana, 10 fatty acids were
      identified of which seven were unsaturated yielding a total unsaturation of
      92.42%. The oil contained essential fatty acids that is, Linoleic (1.34%),
      Linolenic (10.31%), Arachidonic (0.60%) and varying levels of unsaturated higher
      fatty acids, namely, Eicosatrienoic (3.39%), Erucic (3.46%) and Nervonic (1.23%)
      acids. The level of Oleic acid (72.09%) in the oil was close to the value for H.
      barteri.

PMID- 11991082
TI  - Toxicity of argemone oil: effect on hsp70 expression and tissue damage in
      transgenic Drosophila melanogaster (hsp70-lacZ) Bg9.
AB  - The effect of argemone oil on hsp70 expression and tissue damage was investigated
      by studying beta-galactosidase activity, Western blotting and hybridization, and
      trypan blue staining in the larval tissues of transgenic Drosophila melanogaster
      (hsp70-lacZ)Bg9. Different concentrations of argemone oil were mixed with food
      and third-instar larvae were allowed to feed on them for different time intervals
      (2, 4, 24, and 48 h). Argemone oil was found to induce hsp70 even in the lowest
      concentration of the adulterant while maximum tissue damage was observed in the
      higher two treatment groups. Malpighian tubules and midgut tissue reflected
      maximum damage as evidenced by both high beta-galactosidase activity and trypan
      blue staining in these tissues. A prior temperature shock treatment to the larvae
      was enough to protect the larvae from argemone oil-induced tissue damage as
      evidenced by little or no trypan blue staining. The present study suggests the
      cytotoxic potential of argemone oil and further strengthens the evidence for the
      use of hsp70 as a biomarker in risk assessment.

PMID- 11991083
TI  - Long-term enhancement of cytochrome P450 2B1/2 expression in rat hepatocyte
      spheroids through adenovirus-mediated gene transfer.
AB  - Tissue-like structures of cells organized in vitro have a great potential for a
      number of clinical and biomedical applications. Cell functions may be modulated
      with gene delivery, improving the characteristics of these structures.
      Hepatocytes that self-assemble into spheroids can be transduced through
      adenovirus-mediated gene transfer. An adenoviral vector (AdGFP) was employed to
      deliver a gene encoding for green fluorescent protein (GFP) in rat hepatocyte
      spheroids. GFP fluorescence was detected for at least one month. Furthermore, the
      rat cytochrome P450 2B1 gene (CYP2B1) was transferred through infection with a
      recombinant adenovirus (AdCYP2B1) in hepatocyte spheroids cultured in suspension.
      The CYP2B1/2 mRNA and apoprotein levels were continuously higher for over 23 days
      compared to phenobarbital-induced and control cultures. P450-catalyzed
      pentoxyresorufin-O-dealkylation activity was also high in the AdCYP2B1-infected
      spheroids. In these spheroid cultures, albumin and urea levels were similar to
      those in uninfected spheroid cultures, indicating that expression of the CYP2B1
      transgene did not impair these liver-specific functions. Hepatocyte spheroids
      transduced by recombinant adenoviral vectors can be efficiently used for drug
      metabolism studies, in implantation, and in bioartificial liver devices.

PMID- 11991084
TI  - Cadmium-induced apoptosis of primary epithelial lung cells: involvement of Bax
      and p53, but not of oxidative stress.
AB  - The lung is a target organ for cadmium (Cd) toxicity. Apoptosis induced by
      cadmium acetate (CdAc) was studied in alveolar type 2 cells and Clara cells
      isolated from rat lung. Relatively low concentrations of CdAc (1-10 micromol/L)
      induced apoptosis after exposure for 20 h. Type 2 cells were more sensitive than
      Clara cells to Cd-induced apoptosis and loss of cell viability. On exposure to 10
      micromol/L CdAc, the levels of the apoptosis-modulating proteins p53 and Bax were
      increased at 2 h and 5-12 h, respectively. The expression of p53 preceded the
      expression of Bax and the apoptotic process. The exposure to 10 micromol/L CdAc
      did not significantly increase the formation of cellular reactive oxygen species
      (ROS). However, after exposure to a high concentration of CdAc (100 micromol/L),
      a 30% increase of the ROS level was observed. No significant nitric oxide
      production was measured following CdAc exposure. Catalase, superoxide dismutase,
      dimethyl sulfoxide, or tetramethylthiourea did not protect against Cd-induced
      apoptosis. In conclusion, the results show that Clara cells and type 2 cells are
      sensitive to Cd-induced apoptosis. Increased levels of p53 and Bax are suggested
      to be involved in the apoptosis. The apoptosis did not appear to be mediated by
      oxidative pathways.

PMID- 11991085
TI  - Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat
      thymocytes: a possibility of aspartame toxicity.
AB  - Aspartame is a widely used artificial sweetener added to many soft beverages and
      its usage is increasing in health-conscious societies. Upon ingestion, this
      artificial sweetener produces methanol as a metabolite. In order to examine the
      possibility of aspartame toxicity, the effects of methanol and its metabolites
      (formaldehyde and formate) on dissociated rat thymocytes were studied by flow
      cytometry. While methanol and formate did not affect cell viability in the
      physiological pH range, formaldehyde at 1-3 mmol/L started to induce cell death.
      Further increase in formaldehyde concentration produced a dose-dependent decrease
      in cell viability. Formaldehyde at 1 mmol/L or more greatly reduced cellular
      content of glutathione, possibly increasing cell vulnerability to oxidative
      stress. Furthermore, formaldehyde at 3 mmol/L or more significantly increased
      intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner.
      Threshold concentrations of formaldehyde, a metabolite of methanol, that affected
      the [Ca2+]i and cellular glutathione content were slightly higher than the blood
      concentrations of methanol previously reported in subjects administered abuse
      doses of aspartame. It is suggested that aspartame at abuse doses is harmless to
      humans.

PMID- 11991086
TI  - Involvement of gelatinases (MMP-2 and MMP-9) in the development of airway
      inflammation and pulmonary fibrosis.
AB  - Pulmonary fibrosis has an aggressive course and is usually fatal an average of 3
      to 6 years after the onset of symptoms. Pulmonary fibrosis is associated with
      deposition of extracellular matrix (ECM) components in the lung interstitium.
      Matrix metalloproteinases (MMPs) are a major group of proteinases known to
      regulate the ECM remodeling and so they are hypothesized to be important in the
      process of lung fibrosis. These led to the concept that modulation of airway
      remodeling including excessive proteolytic damage of the tissue may be of
      interest for future treatment. The excessive airway remodeling as a result of an
      imbalance in the equilibrium of the normal processes of synthesis and degradation
      of extracellular matrix components could argue in favor of antiprotease
      treatments. Moreover, these observations emphasize that effective therapies for
      these disorders must be given early in the natural history of the disease, prior
      to the development of expensive lung destruction and fibrosis.

PMID- 11991087
TI  - Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12
      cells.
AB  - Neurotoxicity is the dose-limiting side-effect of vincristine in cancer therapy.
      Using the nerve growth factor (NGF)-dependent neurite outgrowth and cell
      proliferation of the PC12 pheochromocytoma cell line as an in vitro assay, the
      protective effect of different intravenous anesthetics was assessed. Vincristine
      (1 nmol/L) significantly decreased the percentage of neurite-forming cells from
      68% +/- 9% to 27% +/- 7% within a 3-day incubation period. The longer neurites (>
      2 x cell body) in particular proved to be extremely sensitive to vincristine
      (from 17% +/- 4% to 0% of total neurite-expressing cells). Flow cytometry results
      revealed an S-phase percentage of 15.85% +/- 3.25% after NGF induction, with
      vincristine reducing this percentage to 0.68% +/- 0.38%. Reversal of the
      inhibitory effect of vincristine was noted in the cells treated with thiopental
      or propofol but not etomidate. Bicuculline partially antagonized the protective
      effect of thiopental and propofol in both studies. We conclude that thiopental
      and propofol, but not etomidate, have a protective effect in vincristine-induced
      neurotoxicity. The protective effect produced by thiopental and propofol is
      probably secondary to activation of GABAA receptors.

PMID- 11991088
TI  - The pulmonary artery catheter.

PMID- 11991089
TI  - The acute respiratory distress syndrome: recent advances in ventilation.

PMID- 11991090
TI  - Management of acute renal failure on the intensive care unit.

PMID- 11991091
TI  - Medical professionalism in the new millennium: a physicians' charter*.
AB  - The practice of medicine in the modern era is beset with unprecedented challenges
      in virtually all cultures and societies. These challenges centre on increasing
      disparities between the legitimate needs of patients, the available resources to
      meet those needs, the increasing dependence on market forces to transform
      healthcare systems, and the temptation for physicians to forsake their
      traditional commitment to the primacy of patients' interests. To maintain the
      fidelity of medicine's social contract during this turbulent time, we believe
      that physicians must reaffirm their active dedication to the principles of
      professionalism, which entails not only their personal commitment to the welfare
      of their patients but also collective efforts to improve the healthcare system
      for the welfare of society. This Charter on Medical Professionalism is intended
      to encourage such dedication and to promote an action agenda for the profession
      of medicine that is universal in scope and purpose.

PMID- 11991092
TI  - Obstetric medicine training: picking up where the licentiate in midwifery left
      off.
AB  - Obstetric medicine is the care of women with medical problems in pregnancy.
      Medical problems may predate or arise de novo in pregnancy. Some are common and
      some are dangerous. Both obstetricians and physicians recognise the need for
      greater numbers of appropriately trained clinicians to care for such women. There
      is a demand for such training, particularly from trainee obstetricians. The Royal
      College of Obstetricians and Gynaecologists (RCOG) and the Royal College of
      Physicians (RCP) agree that there is a need for more formalised training in
      maternal/obstetric medicine and they are working together to develop special
      interest training in maternal medicine. The training will be open to both
      obstetricians and physicians and include theoretical and practical components.
      The practical training will take place in centres with established medical
      obstetric clinics and will be tailored (with appropriate modules) to the amount
      of previous experience in medicine or obstetrics.

PMID- 11991093
TI  - NHS allergy services in the UK: proposals to improve allergy care.
AB  - Allergy is common and its prevalence has increased substantially in the last 2-3
      decades. There has been a particular increase in severe allergic disease,
      including anaphylaxis and food, drug and latex rubber allergy. Provision of
      allergy services in the NHS is poor and there is a huge unmet need. Allergy is a
      full specialty, but there are few consultants and few trainees: only six centres
      in the UK offer a full-time specialist service. Most allergy services are
      provided by doctors--general practitioners and consultants in other specialties-
      with little or no training in allergy. Whilst specialists in other areas of
      medicine have a role in the management of allergy, it is no longer adequate to
      devolve most allergy care to them. The lack of special care leads to morbidity,
      mortality and substantial cost to the NHS, much of it avoidable. To ensure that
      adequate standards of care are satisfactory, allergy care must be led by allergy
      specialists. More consultant posts and training posts in allergy are urgently
      needed; this requires recognition by trust managers, regional commissioners and
      the Department of Health. As a first step, we propose the setting up of
      appropriately staffed regional allergy centres. This could be achieved with a
      central directive and (relatively minor) pump-priming of funding.

PMID- 11991094
TI  - Botulinum toxin in the management of spasticity in adults.
AB  - Botulinum toxin (BTX) is a powerful neurotoxin which blocks cholinergic
      transmission at the neuromuscular junction. Judiciously applied, it can reduce
      local muscle overactivity while maintaining the strength in other muscles. To
      date BTX has not been licensed for use in spasticity in the UK and the literature
      pertaining to clinical practice is still relatively scant. However, controlled
      trials have provided evidence of the effectiveness of BTX both in reducing
      spasticity itself and in achieving functional gain. The guidance given here to
      clinicians involved in the management of spasticity covers the types of patient
      suitable for treatment using BTX, the appropriate dosage, and the necessary
      follow-up procedures and documentation.

PMID- 11991095
TI  - Doctors, patients and the Internet: time to grasp the nettle.
AB  - The Internet, the fastest growing technology in society, has been driven by the
      public's hunger for fast, cheap communication. The modern patient increasingly
      presents to their doctor with an Internet diagnosis and treatment plan, obtained
      from a website with inaccurate or highly biased information. Doctors have limited
      access to the Internet in the workplace and often find it difficult to answer
      specific medical questions using routine search engines. The Internet provides an
      unparalleled opportunity to revolutionise medical education, bedside decision
      making, patient records and communication between professionals and patients.
      Coordination between government, the Royal Colleges and the healthcare industry
      is required to develop the necessary software and hardware to help doctors and
      patients use the Internet to their advantage.

PMID- 11991096
TI  - The NHS plan and clinicians.
AB  - The NHS Plan issued in July 2000 is being implemented and is fundamentally trying
      to modernise the NHS using new organisational arrangements. At its heart is the
      desire to make the NHS more responsive to what the public wants and sensitive to
      individuals' needs and rights. National clinical priorities and targets have been
      identified, including emergency care, time to elective treatment, cancer,
      coronary heart disease, mental health and care of the elderly. Clinical standards
      will be increasingly under scrutiny since the Bristol Royal Infirmary and Alder
      Hey inquiries, and clinicians will expect their performance as individuals, and
      increasingly as team players, to be in the spotlight. There may be a tension
      between achieving safe standards and increased activity levels if shortfalls of
      staffing are not addressed, but ultimately clinicians will need to safeguard
      their standards.

PMID- 11991097
TI  - The NHS English National Service framework for older people: opportunities and
      risks.
AB  - The English National Service Framework (NSF) for Older People conforms to the
      emerging pattern of NSFs as hybrids of policy and evidence, drafted and edited
      within the Department of Health, albeit with external advisory input. Physicians
      welcome its much-needed focus on the needs of older people, but its dynamic
      differs from that underlying the evolution of comprehensive services to date,
      raising concerns that its declared objectives may be unrealised or perversely
      interpreted. This applies to the first three (of eight) 'standards' currently
      being applied: rooting out ageism, the single assessment process and intermediate
      care. With each, there are problems of concept, operational feasibility,
      expertise and accountability for standards. Conversely, the standards for
      subspecialty service models (stroke, falls, mental health) are more significantly
      underpinned by evidence and operational experience. Success overall will depend
      on more clearly defined resource flow and accountability, career recruitment,
      research direction and engagement with specialist physicians than are immediately
      apparent in the document.

PMID- 11991098
TI  - The management of thyroid cancer in adults: a review of new guidelines.
AB  - The management of thyroid cancer has been facilitated by the recent publication
      of the Guidelines for the management of thyroid cancer in adults under the
      auspices of the British Thyroid Association and the Royal College of Physicians.
      This is a consensus document that has been developed by a number of key
      investigators in the field. The central tenet of the guidelines is that thyroid
      cancer is a disease which requires specialist care from a multidisciplinary team,
      including an endocrinologist, nuclear medicine physician, thyroid surgeon and
      endocrine pathologist. The guidelines are comprehensive and detailed, covering
      differentiated (papillary and follicular) and medullary cancer of the thyroid.
      They have been written in sections aimed at thyroid cancer specialists, primary
      care physicians, patients and their families. The guidelines are greatly welcomed
      and represent a major step forwards in the co-ordination of specialist care for
      thyroid cancer in the UK.

PMID- 11991099
TI  - Helicobacter pylori: 20 years on.
AB  - Helicobacters are a new genus of bacteria, inhabiting the interface between
      mucosa and lumen of the gut. Microaerophilic, spiral, flagellated and urease
      positive, they possess features necessary for colonisation of the juxtamucosal
      mucus environment. Helicobacter pylori is the major pathogenic species. Once
      attached to the gastric epithelial cells, it incites an immune response
      characterised histologically by the development of active gastritis and
      immunologically by the presence of specific IgG. Persistence of infection is
      ensured by attachment to tissue antigens (eg Lewis B), a vacuolating toxin (VacA)
      which assists the free passage of urea through epithelial cells, and a cytotoxin
      (CagA) which is actually injected into the epithelial cells via a Type IV
      secretion system. Finally, during the typical lifelong chronic infection, two
      important diseases occur. H. pylori alters gastric physiology to cause acid
      hypersecretion and peptic ulcer. Secondly, it damages the acid secreting mucosa
      leading to atrophic gastritis and gastric cancer risk.

PMID- 11991100
TI  - Dr John Clarke: licentiate in midwifery of the Royal College of Physicians of
      London.
AB  - John Clarke was one of ten licentiates in midwifery created by the College of
      Physicians in the late eighteenth century to regularise the growing involvement
      of medical men in obstetrics. He was an excellent clinician and a popular
      teacher. His publications included original observations about puerperal fever,
      nausea and other complications of pregnancy and the management of labour. He
      opposed the attitude of the College that prevented its Fellows from practising
      midwifery and he stridently criticised the College's neglect of the diseases of
      children. Part one of his book on the diseases of children contained the first
      exact description of tetany. Part two was never published because of his early
      death.

PMID- 11991101
TI  - The consultation in art.

PMID- 11991102
TI  - Fraud in research.

PMID- 11991103
TI  - Organisational issues in acute medical care.

PMID- 11991104
TI  - Women in hospital medicine.

PMID- 11991106
TI  - RCP consultant questionnaire survey.

PMID- 11991105
TI  - Duplicate publication.

PMID- 11991108
TI  - Tuberculosis--a missed opportunity?

PMID- 11991107
TI  - General practitioners with special clinical interests.

PMID- 11991109
TI  - Audit of anticoagulation control: a comparison between the performance of a
      hospital anticoagulation clinic and the general practice.

PMID- 11991111
TI  - Lack of integrity in medicine: fraud in research.

PMID- 11991110
TI  - Training and service should be distinct, but intertwined, before and after
      specialist registration.

PMID- 11991113
TI  - Professionalism--time for a new look.

PMID- 11991114
TI  - Improving outcomes for severely ill medical patients.

PMID- 11991115
TI  - The recognition of a sick patient.

PMID- 11991116
TI  - Early management of the critically ill patient.

PMID- 11991117
TI  - An experimental comparison of detector performance for computed radiography
      systems.
AB  - The intrinsic resolution, noise, and signal-to-noise transfer characteristics of
      five commercial digital computed radiography (CR) systems were compared using
      identical experimental methods. The reader/screen combinations evaluated were
      Agfa ADC-Compact/MD-10, Agfa ADC-Compact/MD-30, Agfa ADC-Solo/MD-10, Agfa ADC
      Solo/MD-30, Lumisys CR-2000/MD-10, Fuji FCR-9501 (HQ)/ST-Va, Kodak CR-400/GP-25,
      and Kodak CR-400/HR. Measurements were made at 70 and 115 kVp with 19 mm added
      aluminum filtration. The presampled modulation transfer functions (MTFs) of the
      systems were measured using an edge method. The noise power spectra (NPS) were
      determined by 2D Fourier analysis of uniformly exposed radiographs. The frequency
      dependent detective quantum efficiencies (DQEs) were computed from the MTF, NPS,
      exposure measurements, and computational estimates of the ideal signal-to-noise
      ratios. Using 70 kVp and 0.1-0.12 mm pixel sizes, spatial frequencies of 2.1,
      2.0, 2.2, 1.9, 2.0, 2.0, 2.3, 2.3, and 3.5 cycles/mm were measured at 0.2 MTF for
      the eight reader/screen combinations, respectively. Using 70 kVp, 7.74 x 10(-8)
      C/kg (0.3 mR), and 0.1-0.12 mm pixel sizes, DQE(0.15) values of 20.3%, 22.9%,
      24.6%, 28.6%, 22.2%, 30.0%, 29.5%, and 17.3% were obtained for the eight
      combinations, respectively. The corresponding values at 115 kVp were 15.9%,
      18.5%, 21.5%, 21.8%, 15.3%, 23.1%, 22.3%, and 13.8%, respectively. The findings
      of the study demonstrate the pixel size, orientation, beam quality, screen, and
      reader dependencies of image quality in CR systems. The physical performance of
      the systems having standard-resolution screens demonstrated similar resolution
      performance but more notable variations in DQE. The one high-resolution screen
      tested had reduced DQE and increased MTF at high frequencies.

PMID- 11991118
TI  - Analysis of trabecular bone texture by modified Hurst orientation transform
      method.
AB  - There is a growing need for noninvasive and inexpensive methods that can
      effectively be used on a large scale, to detect an onset of early osteoarthritis
      in human knee joints. Of many possible options, fractal analysis of two
      dimensional projection x-ray images of trabecular bone (TB) texture, appears as
      one of the best approaches. However, there are some problems associated with the
      characterization of the roughness and anisotropy of the bone texture. To resolve
      these problems, a modified Hurst orientation transform (HOT) method, previously
      developed by the authors, has been used in this study. The advantages of the HOT
      method over other techniques used to analyze bone texture, are that it calculates
      a two-dimensional fractal dimension in all possible directions and also provides
      a measure of anisotropy for both surfaces exhibiting strong anisotropy and
      surfaces exhibiting weak anisotropy. In this study, the accuracy of the HOT
      method in measuring the bone texture roughness and anisotropy; together with the
      effects of image noise, blur, exposure, magnification, and projection angle on
      its performance were investigated. Computer-generated images of fractal surfaces
      and x-ray images obtained for a human tibia head were used. Results obtained show
      that the HOT method can effectively be used to characterize the roughness and
      anisotropy (isotropy) of TB texture.

PMID- 11991119
TI  - Depth dose enhancement of electron beams subject to external uniform longitudinal
      magnetic fields: a Monte Carlo study.
AB  - We studied the dose distributions from electron beams subjected to a longitudinal
      magnetic field applied to them before they reach the phantom. We found that
      specific combinations of the length and intensity of the magnetic field produced
      enhancement of the peaks of the central-axis depth-dose distributions. The EGS4
      Monte Carlo system was used in this study. In the simulations, a uniform axial
      magnetic field parallel to the electron beam direction was applied to the air gap
      between the collimation and the phantom. We extensively studied the simplified
      case of an 18 MeV electron beam point source. Dose deposition was calculated for
      various magnetic field strengths, distances through which the magnetic field was
      applied, collimation sizes, and source to collimation distances. The magnetic
      field strengths varied from 0 to 3 T, the source-to-collimation distances studied
      were 50 and 95 cm, the collimation sizes studied were 10 x 10 and 20 x 20 cm2,
      and the distance through which the field was applied ranged from 10 to 20 cm.
      Specific combinations of these variables resulted in as much as a 70% enhancement
      of the peak dose relative to the surface dose. Finally, to determine how the
      geometry of a real accelerator affects the resulting dose distribution, we
      performed a full simulation of an Elekta SL20 linear accelerator and compared the
      results with the ideal case.

PMID- 11991120
TI  - Effect of phantom voxelization in CT simulations.
AB  - In computer simulations of x-ray CT systems one can either use continuous
      geometrical descriptions for phantoms or a voxelized representation. The
      voxelized approach allows arbitrary phantoms to be defined without being confined
      to geometrical shapes. The disadvantage of the voxelized approach is that
      inherent errors are introduced due to the phantom voxelization. To study effects
      of phantom discretization, analytical CT simulations were run for a fan-beam
      geometry with phantom voxel sizes ranging from 0.0625 to 2 times the
      reconstructed pixel size and noise levels corresponding to 10(3) - 10(7) photons
      per detector pixel prior to attenuation. The number of rays traced per detector
      element was varied from 1 to 16. Differences in the filtered backprojection
      images caused by changing the phantom matrix sizes and number of rays traced were
      assessed by calculating the difference between reconstructions based on the
      finest matrix and coarser matrix simulations. In noise free simulations, all
      phantom matrix sizes produced a measurable difference in comparison with the
      finest phantom matrix used. When even a small amount of noise was added to the
      projection data, the differences due to the phantom discretization were masked by
      the noise, and in all cases there was almost no improvement by using a phantom
      matrix that was more than twice as fine as the reconstruction matrix. No
      substantial improvement was achieved by tracing more than 4 rays per detector
      pixel.

PMID- 11991121
TI  - Design considerations for a computer controlled multileaf collimator for the
      Harper Hospital fast neutron therapy facility.
AB  - The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron
      is collimated using a unique multirod collimator (MRC). A computer controlled
      multileaf collimator (MLC) is being designed to improve efficiency and allow for
      the future development of intensity modulated radiation therapy with neutrons.
      For the current study the use of focused or unfocused collimator leaves has been
      studied. Since the engineering effort associated with the leaf design and
      materials choice impacts significantly on cost, it was desirable to determine the
      clinical impact of using unfocused leaves in the MLC design. The MRC is a useful
      tool for studying the effects of using focused versus unfocused beams on beam
      penumbra. The effects of the penumbra for the different leaf designs on tumor and
      normal tissue DVHs in two selected sites (prostate and head and neck) was
      investigated. The increase in the penumbra resulting from using unfocused beams
      was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm
      for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom
      scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10
      cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue
      in a prostate and head and neck case showed that the dosimetric disadvantages of
      using an unfocused rather than focused beam were minimal and only significant at
      shallow depths. For the rare cases, where optimum penumbra conditions are
      required, a MLC incorporating tapered leaves and, thus, providing focused
      collimation in one plane is necessary.

PMID- 11991122
TI  - Dosimetric characteristics of the DRAXIMAGE model LS-1 1-125 interstitial
      brachytherapy source design: a Monte Carlo investigation.
AB  - (Received 5 June 2001; accepted for publication 26 December 2001; published 19
      March 2002) We have used Monte Carlo photon transport simulations to evaluate
      dosimetric characteristics of a new 125I seed, the DRAXIMAGE BrachySeed (model LS
      1) source for interstitial brachytherapy and to calculate the dosimetric
      parameters recommended by the AAPM Task Group 43 (TG-43). To eliminate thick end
      welds, preformed closed-ended Ti shells are welded together near the transverse
      plane. The radioactivity is localized near the seed ends in order to maximize
      isotropy at typical prescription distances. Transmission radiography reveals that
      its internal components can move by as much as 200 microm under the influence of
      gravitational forces affecting the dose-rate constant and relative dose
      distribution by as much as 5% and 10%, respectively. However, the clinical dose
      distribution can be well represented by a weighted average of dose distributions
      corresponding to three different orientation-dependent internal geometry
      configurations. This average dose distribution agrees closely (within 1% at 1 cm)
      with that derived from the geometry specified by the vendor model (seed
      components uniformly spaced), from which the recommended relative dosimetry
      parameters were derived. An average dose-rate constant of 0.935 cGy h(-1) U(-1)
      is recommended for clinical application and values of 0.919, 0.963, and 0.920 for
      vertical orientation, horizontal orientation, and the vendor specified
      geometries, respectively. The NIST wide-angle free-air chamber realization of the
      air-kerma strength primary standard, SKN99, was explicitly simulated. We show
      that the output of Ag characteristic x rays is about half that of the model 6711
      source resulting in a relative dose distribution between that of the model 6711
      source and pure 125I x-ray emitters. Finally, it is demonstrated that the TG-43
      point-source formalism more accurately estimates solid-angle weighted dose at
      small distances if one uses a radial dose function data prepared using a point
      source, rather than line-source, geometry factor.

PMID- 11991123
TI  - A simplified intensity modulated radiation therapy technique for the breast.
AB  - A simplified intensity modulated radiation therapy (sIMRT) technique for the
      breast is presented. The technique aims to produce a uniform dose distribution in
      the entire breast volume. Using the standard tangential beam arrangement, we
      first determine for each pencil beam the midpoint of the segment that intersects
      the treatment volume. The dose to the midpoint from the open field is then
      calculated. The intensity of the pencil beam is determined as proportional to the
      inverse of the open field dose. With this intensity modulated beam, the dose
      delivered to the midpoint of each pencil beam segment that intersects the
      treatment volume is now equalized. The dose distribution in the entire treatment
      volume is nearly as uniform as can be achieved under the given beam arrangement.
      Fifteen left breast patients were planned with the sIMRT technique. For
      comparison, the same group of patients was also planned with the standard wedged
      pair technique and the full-fledged volume-based IMRT (vIMRT) technique. Both the
      sIMRT and the vIMRT techniques achieved more homogeneous dose in the treatment
      volume than the standard plan. Doses to the heart, the ipsilateral lung, and the
      contralateral breast were also reduced. The planning time and the treatment time
      for the sIMRT technique were comparable to that of the standard technique, and
      significantly less than that required by the vIMRT technique. The sIMRT technique
      is practical for large-scale implementation in a busy clinic without requiring
      significant increase of resources.

PMID- 11991124
TI  - Dosimetric effects of source-offset in intravascular brachytherapy.
AB  - In intravascular brachytherapy (IVBT), radioactive sources can be displaced
      (offset) laterally from the center of the lumen and/or longitudinally from the
      desired location due to the cardiac motion and/or the absence of a source
      centering device. The purpose of this work is to study the dosimetric impact of
      such a source offset. Dose effects of both lateral and longitudinal source
      offsets with or without the presence of a calcified plaque or a metallic stent
      are calculated for the three most commonly used sources (32P, 90Sr/90Y, and
      192Ir). The MCNP Monte Carlo code is used in the calculation. Static and random
      source offsets are considered. The major results include that (a) dose can be
      changed significantly (by a factor of up to 4) due to a static lateral source
      offset; (b) this dose variation is reduced if the lateral source offset is
      considered as random moving within the vessel (the dose at the 2 mm reference
      radial distance is increased by 5-15% for the three sources in the case of the 2D
      random offset studied); (c) the presence of a calcified plaque and/or a metallic
      stent worsens the dosimetric effects; (d) the longitudinal random source offset
      results in a reduction (15-18%) in the effective treatment length; (e) the dose
      effects of source offsets for the beta source are higher than those for the gamma
      source. The data presented in this paper may be used for IVBT treatment planning
      or for dosimetric analysis of treatment outcome. The dose change due to the
      source offset should be considered in dose prescription. The reduction of
      effective treatment length should be taken into account in selection of a proper
      source length to ensure an adequate coverage of the treatment target.

PMID- 11991125
TI  - Dosimetric characteristics of the CDC-type miniature cylindrical 137Cs
      brachytherapy sources.
AB  - The low dose rate CDC-type miniature cylindrical 137Cs sources are available,
      with one or three active beads, for use in source trains in automatic and manual
      afterloading systems for gynecological brachytherapy. Absolute dose rate
      distributions in water have been calculated around these sources using the Monte
      Carlo GEANT3 code and they are presented as conventional two-dimensional
      Cartesian lookup tables. The AAPM Task Group 43 formalism for dose calculation
      has been also applied. The dose rate constant obtained for the one bead source is
      lambda = 1.113 +/- 0.003cGyh(-1) U(-1), and the value for the three bead source
      is A= 1.103 +/- 0.003cGyh(-1) U(-1). Finally, for the treatment planning systems
      based on Sievert-type algorithms, the attenuation coefficients that best
      reproduce Monte Carlo dose rate distribution are given.

PMID- 11991126
TI  - Monte Carlo dosimetry of a tandem positioned beta-emitting intravascular
      brachytherapy source train.
AB  - Prevention of restenosis following interventional coronary procedures with
      catheter based beta-emitting sources is currently under clinical trial
      investigations. Systems utilizing fixed length source trains limit the
      clinician's ability to increase the radiation source length as required. A
      technique known as "pull back" is used when the segment of artery requiring
      radiation is longer than the available fixed length source train. In this
      instance, tandem positioning of the fixed length source is used to treat the
      longer length of artery. The aim of this study was to examine the dosimetry of
      the junction region associated with pull back treatments using a commercially
      available 90Sr/Y catheter based intravascular brachytherapy source train. Dose
      profiles were calculated, using the Monte Carlo code MCNP4B, at radial distances
      of 1.5, 2.0, and 2.5 mm for pull back techniques using 2.5 mm overlapping,
      abutting, and 2.5 mm spaced source trains. Results at the protocol prescription
      radius of 2 mm showed a junction dose elevated 61% above prescription for 2.5 mm
      overlapping source trains. For 2.5 mm spaced trains, this figure falls to 64%
      below prescription dose. In contrast, abutted source trains exhibited only a 1%
      depression below prescription dose in the junction region. The reference point
      dose rate per unit activity of this source was found to be consistent with
      previous studies.

PMID- 11991127
TI  - Efficient simulation of SPECT down-scatter including photon interactions with
      crystal and lead.
AB  - A major image degrading factor in simultaneous Dual Isotope (DI) SPECT or
      simultaneous Emission-Transmission (ECT-TCT) imaging, is the detection of photons
      emitted by the higher energy isotope in the energy window used for imaging the
      lower energy isotope. In Tc-99m/Tl-201 DI-SPECT typically tens of percents of the
      total detected down-scatter is caused by lead x rays. In Tc-99m/Gd-153 ECT-TCT, a
      comparable fraction of the down-scatter originates from Tc-99m photons which only
      partly deposit their energy in the detector crystal (i.e., due to crystal
      interactions). Efficient simulation methods which model down-scatter can be used
      to optimize DI-SPECT or ECT-TCT imaging acquisition or reconstruction protocols.
      In this paper we adapt a previously proposed efficient down-scatter simulation
      method, to include the interactions of photons with the detector crystal and
      collimator lead. To this end, point spread function tables including crystal and
      lead interactions are precalculated. Subsequently, photons are traced through the
      patient body until their last scatter position, and the precalculated responses
      are used to project the photons onto the detector plane, while photon attenuation
      in the patient is taken into account. The approach is evaluated by comparing
      simulated Tc-99m down-scatter projections with measured projections.
      Incorporation of photon interaction with crystal and lead leads to significantly
      improved accuracy of the shape of down-scatter responses, while differences in
      total counts between simulated and measured projections typically decrease from
      tens of percents to a couple of percents. Calculating 60 down-scatter projections
      of an extended distribution on a 64 x 64 x 64 grid takes about three minutes on a
      PC with two 1.2 GHz processors. We conclude that accurate and efficient
      simulation of down-scatter is now possible including the major effects of the
      nonuniform mass density of the patient as well as photon interactions with the
      crystal and collimator lead.

PMID- 11991128
TI  - Quality assurance in stereotactic space. A system test for verifying the accuracy
      of aim in radiosurgery.
AB  - A detailed quality assurance (QA) program is essential for high precision single
      dose irradiations. The accuracy of stereotactic radiosurgery is limited by the
      errors of each step in the chain for optimal treatment beginning with the
      diagnostic imaging and target localization leading to the dose planning and
      ending up with the treatment of the patient. Two main goals were followed on the
      way to finding a concept for a suitable and sufficient quality assurance routine.
      First, the chain of items in terms of a complete patient simulation should be
      followed and second, the stereotactic MR image data should be verified against a
      reference in our case stereotactic radiographic projection images. Target point
      verifications were performed using the so-called, unknown target method based on
      MRI, CT, and stereotactic projection images. A marked radiochromic film, embedded
      between inserts of the phantom is fixed parallel to either the xy or the xz plane
      of the stereotactic coordinate system. After imaging and planning, the phantom is
      adjusted and irradiated. At the end, the film, dyed by the radiation field around
      the premarked cross, is evaluated. The measured distance between the unit center
      point (shadow) and the localization of the marked film leads to the deviation to
      be minimized. This is referred to as the displacement vector. The results,
      evaluating 170 system tests within 5 years. show that the mean displacement
      vector of the complete system is 0.48 mm +/-0.23 mm (mean+/- sd). Factors having
      a significant influence on the overall accuracy are associated with MRI
      parameters. Test results based on axial images (xy plane; 0.42 mm +/- 0.24 mm)
      are significantly superior to coronal images (xz plane; x = 0.60 mm +/- 0.02 mm).
      Further on, the 3D-mpr sequence (0.40 mm +/- 0.19 mm) is significantly superior
      to the T1 weighted SE sequences (0.66 mm +/- 0.24 mm). Given the high mechanical
      accuracy of the Leksell gamma knife, the most sensitive technical factor having
      an influence on the overall precision of radiosurgery is the MRI study. However,
      using the appropriate imaging sequences and parameters the dislocation error
      inferred by MRI can be kept very low and restricted to the rare patient inherent
      distortion factors. With these precautions in mind, MRI is recommended as the
      imaging method of choice in radiosurgery.

PMID- 11991129
TI  - Relative effectiveness of polyacrylamide gel dosimeters applied to proton beams:
      Fourier transform Raman observations and track structure calculations.
AB  - The feasibility of using polyacrylamide gel (PAG) to characterize a clinically
      relevant 74 MeV proton beam has been considered. Fourier transform Raman
      spectroscopy has been used to measure the response (i.e., consumption of monomer)
      of PAG exposed to the central and end portions of a spread out Bragg peak (SOBP),
      i.e., in two regions with measurable difference in proton linear energy transfer
      (LET). The response curve in each region was compared with a typical 6 MV x-ray
      irradiated gel response curve, thus arriving at a gel "relative effectiveness"
      (RE) in each of the two regions. In addition, the theory of track structure,
      which is typically used to calculate a detector RE, is shown to give reasonable
      agreement when compared with the experimental results. Both experimental and
      track structure results indicate a decrease in gel response when irradiated with
      protons, as compared with the x-ray response. In addition, both sets of results
      indicate a variation in gel response between the mid and end SOBP regions, thus
      illuminating the dependence of gel response to proton LET. The physical
      phenomenon causing a lower proton versus x-ray gel response may be understood by
      considering the track structure calculations, which indicate that gel
      radiosensitive elements close to the track of a proton (i.e., within 1.5 x 10(-6)
      cm) are saturated. This saturation is due to the high delta-ray doses deposited
      in these regions. The track calculations are extended to other situations (e.g.,
      raw BP, different gel compositions) where experimental determination of RE is
      difficult or time consuming. Results again indicate a gel response dependent on
      position in the depth dose curve (i.e., LET). Overall, this study illuminates the
      difficulty in using polyacrylamide gel to extract quantitative dose maps when
      exposed to proton radiation.

PMID- 11991130
TI  - Reconstruction of electron spectra using singular component decomposition.
AB  - Reconstruction of electron spectra of medical accelerators from measured depth
      dose distributions is an attractive tool for commissioning of a Monte Carlo
      treatment planning system. However, the reconstruction method is an inverse
      radiation transport problem which is poorly conditioned, in the sense it may
      become unstable due to small perturbations in the input data. Predicting the
      sharp (delta-like) peak in the electron spectrum provides an additional challenge
      for the numerical reconstruction technique. To improve efficiency and robustness
      of the reconstruction technique, we developed an algorithm based on a separation
      of the electron spectrum into singular and regular components. We approximate the
      singular peak of the spectrum by a narrow weighted Gaussian function. The
      parameters of this Gaussian function are sought using only the fall-off and toe
      regions of the depth-dose curve. Analytical representation of the spectral peak
      by a Gaussian has benefit since only one weight and the mean and variance must be
      derived from the depth-dose curve instead of multiple spectra weights. The
      regular part of the spectrum is reconstructed from the residual depth-dose
      distribution using a variational method combined with a regularization technique
      to avoid the nonphysical oscillations. The effectiveness of the method is
      demonstrated by comparing predictions to "benchmark" spectra and depth-dose
      distributions from Monte Carlo simulation of medical accelerators.

PMID- 11991131
TI  - Improved computed radiography image quality from a BaFl:Eu photostimulable
      phosphor plate.
AB  - Recent advances in the design of photostimulable phosphor (PSP) plates for
      computed radiography (CR) systems have made it possible to manufacture plates
      made of BaFI:Eu phosphor material in the cassette form. The image quality of this
      plate, six BaF(Br,I):Eu plates, and one BaFBr:Eu plate were evaluated in terms of
      presampling modulation transfer function (MTF), normalized Wiener spectra (WSN),
      and detective quantum efficiency (DQE). Compared with the best-performing
      BaF(Br,I):Eu plate, the BaFI:Eu plate provided DQE that was higher, at spatial
      frequencies of 0.5, 1.0, and 2.0 cycles/mm, by 12% (21.8 versus 19.4), 13% (18.8
      versus 16.7), and 11% (12.0 versus 10.8), respectively. Since presampling MTF
      values of the two plates were comparable, the BaFI:Eu plate's higher DQE is
      attributable to total WSN conversely being lower by 17% [8.65 x 10(-5) (mm2)
      versus 10.38 x 10(-5) (mm2)], 17% [5.85 x 10(-5) (mm2) versus 7.03 x 10(-5)
      (mm2)], and 12% [2.82 x 10(-5) (mm2) versus 3.19 x 10(-5) (mm2)] at the specified
      frequencies, respectively, primarily due to the contribution of x-ray quantum
      WSN. This jibes with the high x-ray absorption provided by the 27%-higher x-ray
      attenuation coefficients (7.54 versus 6.07, at 60 KeV) that BaFI offers over
      BaF(Br(0.85),I(0.15)), a result of the high atomic number of BaFI's exclusively
      iodine halide content. The results were consistent with earlier studies of
      several of these same plates and indicate that BaFI:Eu is a promising avenue to
      lower image noise and higher overall CR system image quality.

PMID- 11991132
TI  - Dose to radiation therapists from activation at high-energy accelerators used for
      conventional and intensity-modulated radiation therapy.
AB  - The increased beam-on times which characterize intensity-modulated radiation
      therapy (IMRT) could lead to an increase in the dose received by radiation
      therapists due to induced activity. To examine this, gamma ray spectrometry was
      used to identify the major isotopes responsible for activation at a
      representative location in the treatment room of an 18 MV accelerator (Varian
      Clinac 21EX). These were found to be 28Al, 56Mn, and 24Na. The decay of the dose
      rate measured at this location following irradiation was analyzed in terms of the
      known half-lives to yield saturation dose rates of 9.6, 12.4, and 6.2 microSv/h,
      respectively. A formalism was developed to estimate activation dose
      (microSv/week) due to successive patient irradiation cycles, characterized by the
      number of 18 MV fractions per week, F, the number of MU per fraction, M, the in
      room time between fractions, td (min), and the treatment delivery time t'r (min).
      The results are represented by the sum of two formulas, one for the dose from
      28Al 1.8 x 10(-3) F M (1-e(-03t'(r))/t'r and one for the dose from the other
      isotopes approximately 1.1 x 10(-6) F(1.7) Mt(d). For conventional therapy doses
      are about 60 microSv/week for an 18 MV workload of 60,000 MU/week. Irradiation
      for QA purposes can significantly increase the dose. For IMRT as currently
      practiced, lengthy treatment delivery times limit the number of fractions that
      can be delivered per week and hence limit the dose to values similar to those in
      conventional therapy. However for an IMRT regime designed to maximize patient
      throughput, doses up to 330 microSv/week could be expected. To reduce dose it is
      recommended that IMRT treatments should be delivered at energies lower than 18
      MV, that in multienergy IMRT, high-energy treatments should be scheduled in the
      latter part of the day, and that equipment manufacturers should strive to
      minimize activation in the design of high-energy accelerators.

PMID- 11991133
TI  - Monte Carlo-aided dosimetry of the theragenics TheraSeed model 200 103Pd
      interstitial brachytherapy seed.
AB  - A dosimetric study of a 103Pd seed for permanent interstitial brachytherapy, the
      Theragenics Corporation Model 200 (TheraSeed), has been undertaken utilizing
      Monte Carlo photon-transport (MCPT) simulations. All dosimetric quantities
      recommended by the American Association of Physicists in Medicine (AAPM) Task
      Group 43 (TG-43) [Med. Phys. 22, 209-234 (1995)] report have been calculated.
      This source contains graphite pellets coated with palladium metal, within which
      the radioactive 103Pd is distributed. Due to the significant influence of this
      metal coating thickness on the dose distribution, two coating thicknesses, 2.2
      microm (light seed, representing currently available seeds) and 10.5 microm
      (heavy seed, representing reactor-produced seeds available before 1994), were
      analyzed. Quantities determined are the following: dose rate constant, radial
      dose function, anisotropy function, anisotropy factor, anisotropy constant, and
      "along and away" dose tables. The National Institute of Standards and Technology
      (NIST) Wide Angle Free Air Chamber (WAFAC) standard for air-kerma strength
      (SK,N99) was simulated, allowing a comparison to measured dosimetry data
      normalized to SKN99. The calculated dose-rate constants are 0.691 (light seed)
      and 0.694 cGy h(-1) U(-1) (heavy seed), where 1 U= 1 microGy x m2 x h(-1), in
      contrast to the recommended TG-43 value of 0.74 cGy h(-1) U(-1) and the value,
      0.665 cGy h(-1) U(-1), recommended by AAPM report 69 [Med. Phys. 27, 634-642
      (2000)]. Anisotropy constants (1/r2 weighted average, r > or = 1 cm) are 0.862
      and 0.884 for the light seed and heavy seed, respectively. A generalization of
      the AAPM formalism [Med. Phys. 27, 634-642] for evaluating the time-dependent
      ratio of an administered-to-prescribed dose is presented. The findings of this
      study, in combination with 5% corrections applied to WAFAC measurements performed
      in 1999, imply that changes in the AAPM's recommended ratios as large as 6%, are
      indicated.

PMID- 11991134
TI  - Temperature dependence of commercially available diode detectors.
AB  - Temperature dependence of commercially available n- and p-type diodes were
      studied experimentally under both high instantaneous dose rate (pulsed) and low
      dose rate (continuous) radiation. The sensitivity versus temperature was measured
      at SSD = 80 or 100 cm, 10 x 10 cm2, and 5 cm depth in a 30 x 30 x 30 cm3 water
      phantom between 10 degrees C and 35 degrees C. The response was linear for all
      the diode detectors. The temperature coefficient (or sensitivity variation with
      temperature, svwt) was dose rate independent for preirradiated diodes. They were
      (0.30 +/- 0.01)%/degrees C, (0.36 +/- 0.03)%/degrees C, and (0.29 +/-
      0.08)%/degrees C for QED p-type, EDP p-type, and Isorad n-type diodes,
      respectively. The temperature coefficient for unirradiated n-type diodes was
      different under low dose rate [(0.16 to 0.45)%/degrees C, continuous, cobalt] and
      high instantaneous dose rate [(0.07 +/- 0.02)%/degrees C, pulsed radiation].
      Moreover, the temperature coefficient varies among individual diodes. Similarly,
      the temperature coefficient for a special unirradiated QED p-type diode was
      different under low dose rate (0.34%/degrees C, cobalt) and high instantaneous
      dose rate [(0.26 +/- 0.01)%/degrees C, pulsed radiation]. Sufficient
      preirradiation can eliminate dose rate dependence of the temperature coefficient.
      On the contrary, preirradiation cannot eliminate dose rate dependence of the
      diode sensitivity itself.

PMID- 11991135
TI  - Electron beam collimation with focused and curved leaf end MLCs--experimental
      verification of Monte Carlo optimized designs.
AB  - In general, electron beams from conventional accelerators using applicators with
      lead alloy inserts are not suitable for advanced conformal radiation therapy.
      However, interesting electron treatments have been demonstrated on a few advanced
      accelerators. These accelerators have been equipped with helium filled treatment
      heads and computer controlled MLCs that produce clinically useful energy
      modulated electron beams or mixed photon electron beams in an automated sequence.
      This study analyzes the characteristics of different MLC designs, curved and
      focused leaf ends in helium filled treatment heads, with respect to their effect
      on electron beams. In addition, this study analyzes the effects that different
      treatment head designs have on the output factor due to collimator scattering and
      shielding of secondary sources during treatment. The investigation of the
      different treatment head designs was performed with the Monte Carlo package BEAM
      and was verified by experimental methods. The results show that the difference
      between curved leaf ends and focused ends is negligible in most practical cases.
      The results also show the importance of scattering foil optimization in the
      optimization of parameters such as penumbra, virtual source position, and in the
      reduction of the output variation. In all cases, the experimental data verifies
      the calculations.

PMID- 11991136
TI  - Point/Counterpoint. There is no legitimate role for an applications service
      provider in radiology.

PMID- 11991137
TI  - Comments on "Comparison of I-125 sources used for permanent interstitial
      implants".

PMID- 11991138
TI  - Comment on "Comparison of 1-125 sources used for permanent interstitial
      implants".

PMID- 11991139
TI  - Synthesis and hybridization studies of a 5-aminopentanoic acid nucleobase (APN)
      dimer.
AB  - We have prepared a 5-aminopentanoic acid nucleobase (APN) dimer and investigated
      its hybridization capabilities to complementary DNA using both UV melting and NMR
      techniques.

PMID- 11991140
TI  - Structural transitions in polycytidylic acid: proton buffer capacity data.
AB  - The pH-dependences of proton buffer capacity of poly(C) were computed on the
      basis of the literature data. In these curves there were observed four peaks: two
      narrow and two wide ones. The first narrow peak reflects the process of
      cooperative formation of double helices, which is induced by protonation of the
      N3 atom of nucleotide bases. The first wide peak is assigned to noncooperative
      process of poly(C) double helices protonation at the N3 nitrogen atom. It is
      proposed that the second wide peak corresponds to noncooperative protonation of
      the neutral cytosine bases at the oxygen atom. This reaction causes cooperative
      dissociation of the poly(C) double helices. The second narrow peak reflects the
      dissociation process.

PMID- 11991141
TI  - Effect of 5-FU substitution and mutation on Sm protein binding to human U4 snRNA.
AB  - The effects of native and non-native nucleotide substitution on the binding of Sm
      proteins to human U4 snRNA were investigated to determine if the Sm site was a
      likely target for the RNA-mediated effects of the anticancer drug 5-FU, and other
      nucleoside analogues. The Sm binding site of human U4 snRNA was prepared by in
      vitro transcription, and Sm protein binding was assessed using gel mobility shift
      assays. The U4:Sm RNA:protein complex was identified by immunoprecipitation with
      the Sm-specific Y12 antibody. The effects of 5-FU substitution were assessed by
      including FUTP in the in vitro transcription reactions. The effects of native
      nucleotide substitution were assessed by mutagenesis. Deletion mutants were used
      to assess the relative importance of the two stem-loops that flank the Sm binding
      site for protein binding. Point mutation (U-->G) to the 5'-Urd in the Sm site
      reduced Sm protein binding while similar point mutation to the 3'-Urd had a
      lesser effect. Mutation (U-->G) of all Urd in the Sm site completely inhibited Sm
      protein binding. The central stem-loop contributed significantly to Sm protein
      complex formation but the 3' stem-loop had little effect. Substitution of Urd by
      5-fluorourdine (FUrd) did not inhibit Sm protein binding, but reduced the
      stability of the resulting complex. The results indicate that 5-FU, or other
      Uracil analogues, are unlikely to exert RNA-mediated effects through inhibition
      of Sm protein binding.

PMID- 11991142
TI  - New synthesis of L-FMAU from L-arabinose.
AB  - A new synthesis of 2'-deoxy-2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil
      (13, L-FMAU) was achieved in 10 steps from L-arabinose.

PMID- 11991143
TI  - Synthesis and biological evaluation of some acyclic alpha-(1H-pyrazolo-[3,4
      d]pyrimidin-4-yl)thioalkylamide nucleosides.
AB  - The chemical synthesis of some acyclic alpha-(1H-pyrazolo[3,4-d]pyrimidin-4
      yl)thioalkylamide nucleosides (10-12)a-c is described. The treatment of IH
      pyrazolo[3,4-d]pyrimidin-4-thione 1 with compounds 2a-c gave, regioselectively,
      ethyl alpha-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)thioalkylates 3a-c, respectively.
      These heterocycles were alkylated, separately, with alkylating agents 4, 5 and 6
      to give, regioselectively, the N1-acyclic nucleosides (7-9)a-c which were
      deprotected to afford the desired products (10-12)a-c. All synthetic compounds
      were characterized on the basis of their physical and spectroscopic properties.
      The products (10-12)a-c were evaluated for their inhibitory effects against the
      replication of HIV-1 (III(B)), HIV-2 (ROD), various DNA viruses, a variety of
      tumor-cell lines and M. tuberculosis. No marked biological activity was found.

PMID- 11991144
TI  - P-chiral oligonucleotides. 2D Roesy NMR assignment of absolute configuration at
      phosphorus and conformational analysis of 5'-O-monomethoxytrityl-(2'-O
      deoxyribonucleoside) 3'-O-[O-(4-nitrophenyl)]methanephosphonates.
AB  - Fast and simple methodology for the assignment of the absolute configuration at
      the phosphorus atom in diastereomerically pure Rp and Sp 5'-O-monomethoxytrityl
      2'-O-deoxynucleoside 3'-O-(O-4-nitrophenyl) methanephosphonate (3) was
      established. The method utilizes 2D ROESY NMR and can be used for the
      stereochemical analysis of other P-chiral mononucleotides. Configurational
      analysis shows that the major conformation of the sugar residue in 3 is of the S
      (South) type. This study will facilitate synthesis of stereoregular
      methylphosphonate oligonucleotide analogues via the transesterification method.

PMID- 11991145
TI  - New method for the preparation of 3'- and 2'-O-phosphoramidites of 2'- and 3'
      difluoromethyluridine derivatives.
AB  - Hydrogenation of 2'-deoxy-2'-difluoromethylene-5'-O-dimethoxytrityluridine (1)
      and 3'-deoxy-3'-difluoromethylene-5'-O-dimethoxytrityluridine (7), gave the
      corresponding 2'- and 3'-difluoromethyluridine derivatives 2a and 8a.
      Detritylation of compounds 2a, 2b and 8a, 8b resulted in the formation of 1-(2
      deoxy-2-C-difluoromethyl-beta-D-arabino-pentofuranosyl)uracil (3a) and 1-(3-deoxy
      3-C-difluoromethyl-beta-D-xylo-pento furanosyl)- uracil (9a) as well as
      corresponding minor isomers 3b and 9b. Compounds 3a and 3b were also obtained
      from 2'-deoxy-2'-difluoromethylene-3',5'-O-(tetraisopropyldisiloxane-1,3
      diyl)uridine (4). Finally, phosphitylation of 2a and 8a provided the title 2'-
      and 3'-O-phosphoramidites 6 and 10.

PMID- 11991146
TI  - Glucopyranosides derived from 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)ones.
AB  - The reaction of 2,3.4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide with a 6
      aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)one in aqueous acetone in the presence
      of KOH furnishes a 4-(beta-D-glucopyranosyloxy)pyrimidine and a 3-(beta-D
      glucopyranosyl)pyrimidine as the major and minor product. respectively.

PMID- 11991147
TI  - Synthesis of novel hydroxymethyl substituted analogues related to carbovir and
      neplanocin A.
AB  - Two enantiomerically pure hydroxymethyl substituted cyclopentene nucleoside
      analogues (42 and 53) related to carbovir and neplanocin A, respectively, were
      prepared from the chiral pool of iridoid glucosides. In addition two saturated
      hydroxymethylated analogues (44 and 45) were obtained from a protected
      intermediate.

PMID- 11991148
TI  - Difficulties in the deprotection of 1,2-ketals in nucleosides containing
      alkylidencarbazoyl groups.
AB  - The synthesis of unprotected alkylidencarbazoyl nucleoside derivatives 8a-8d is
      shown. A direct deprotection route from readily available 2',3'-isopropylidene
      protected nucleosides 5a-5d. prepared from a chemoenzymatic procedure, did not
      give the selective cleavage of the ketal function without affecting the C=N bond.
      The next option tried was to look at the previous compound in the retrosynthetic
      route: 2',3'-protected carbazoyl nucleoside 4. However, in all cases we obtained
      unsatisfactory results. Stepping further back, the hydrolysis of compound 3a led
      us to unprotected carbonate nucleoside 9 in quantitative yield. With this
      compound available, the synthesis towards derivatives 8 was accomplished through
      a known procedure.

PMID- 11991149
TI  - A facile synthesis of cis-4-amino-2-cyclopentene-1-methanol, a key intermediate
      for the synthesis of carbocyclic nucleosides.
AB  - A number of carbocyclic nucleosides can be synthesized from (+/-)-cis-4-amino-2
      cyclopentene-1-methanol (3). Carbocyclic amino alcohol 3 is a key intermediate
      that makes possible the efficient synthesis of the carbocyclic nucleosides. In
      this study we wish to report an efficient synthesis of carbocyclic amino alcohol
      3 from inexpensive and readily available starting material. The synthetic route
      employed cyclopentadiene (4) as a starting material and proceeded in 38% overall
      yield through 6 steps involving a hetero Diels-Alder reaction and an aza-Claisen
      rearrangement.

PMID- 11991150
TI  - Microwave induced synthesis of ribonucleosides on solid support.

PMID- 11991151
TI  - Synthesis and enzymatic characterization of P1-thio-P2-oxo trideoxynucleoside
      diphosphates having AZT, FdU, or dT at the 3'-position.
AB  - Model compounds for oligonucleotide-prodrugs, P1-thio-P2-oxo
      trideoxyribonucleoside diphosphates: d[G(s)C(o)X] and d[T(s)A(o)X] (X = AZT, FdU
      or dT) have been prepared, and their hydrolyses by snake venom phosphodiesterase
      and nuclease S1 are described.

PMID- 11991152
TI  - Synthesis and antiviral evaluation of some new glycosylthioureas containing a
      quinazolinone nucleus.
AB  - A new synthesis of glycosylthioureas containing a quinazolinone nucleus is
      described utilizing per-O-acetylglycopyranosylisothiocyanates and several
      aminoquinazolinones as starting compounds. Structural proofs of these compounds
      are provided from elemental analyses, IR, 1H and 13C NMR spectra and mass
      spectra. The biological activity of these compounds has been studied.

PMID- 11991153
TI  - Prosecution of batterers: views of African American battered women.
AB  - Findings from 207 interviews of urban, African American women indicated that 65%
      of the women said they favored prosecution of their abusers. A logistic
      regression showed that the following independent variables were related to
      significantly decreased odds of opposing prosecution: prosecution being
      initiated, being separated from partner, and abuser's use of alcohol and/or drugs
      during violent incidents in the last 6 months. Bivariate analysis showed that a
      long history of severe abuse by the partner was associated with favoring
      prosecution. The most common reasons that women gave for favoring prosecution
      were that abuse is illegal and not acceptable and that abusers should not violate
      or touch women. The most common reasons for opposing prosecution were that women
      believed the incident was not serious or was the first time he was violent. The
      study can be used to expand discussion about prosecution of batterers.

PMID- 11991154
TI  - Exposure to abuse, neglect, and household dysfunction among adults who witnessed
      intimate partner violence as children: implications for health and social
      services.
AB  - Intimate partner violence (IPV) damages a woman's physical and mental well-being,
      and indicates that her children are likely to experience abuse, neglect and other
      traumatic experiences. Adult HMO members completed a questionnaire about adverse
      childhood experiences (ACEs) including childhood abuse, neglect, and household
      dysfunction. We used their responses to retrospectively assess the relationship
      between witnessing intimate partner violence and experiencing any of the 9 ACEs
      and multiple ACEs (ACE score). Compared to persons who grew up with no domestic
      violence, the adjusted odds ratio for any individual ACE was approximately two to
      six times higher if IPV occurred (p < 0.05). There was a powerful graded increase
      in the prevalence of every category of ACE as the frequency of witnessing IPV
      increased. In addition, the total number of ACEs was increased dramatically for
      persons who had witnessed IPV during childhood. There was a positive graded risk
      for self-reported alcoholism, illicit drug use, i.v. drug use and depressed
      affect as the frequency of witnessing IPV increased. Identification of victims of
      IPV must include screening of their children for abuse, neglect and other types
      of adverse exposures, as well as recognition that substance abuse and depressed
      affect are likely consequences of witnessing IPV. Finally, this data strongly
      suggest that future studies, which focus on the effect of witnessing IPV on long
      term health outcomes, may need to take into consideration the co-occurrence of
      multiple ACEs, which can also affect these outcomes.

PMID- 11991155
TI  - A model for predicting dating violence: anxious attachment, angry temperament,
      and need for relationship control.
AB  - Structural equation modeling (SEM) was used to test a model incorporating anxious
      attachment, angry temperament, and attempts to control one's partner as
      predictors of the severity and frequency of dating violence. To date, these
      concepts have not been clearly established as having direct or indirect effects
      on dating violence. It was hypothesized that anxious attachment and angry
      temperament would influence the need for and attempts to control one's partner
      which, in turn, would predict a person's actual use of force. College students
      (213 males; 199 females) completed measures assessing these constructs. Cross
      validation was accomplished through using two successive freshmen samples.
      Statistics indicated the application of the model fit well to both samples. All
      specified paths were significant except for the direct path from anxious
      attachment to need for control in the second sample. While exploratory, this
      model seemed satisfactory for explaining potentially causal relationships of
      attachment, anger, and attempts to control one's partner leading to dating
      violence.

PMID- 11991156
TI  - The relationships among childhood abuse, borderline personality, and self-harm
      behavior in psychiatric inpatients.
AB  - The current study was undertaken to explore the relationships among childhood
      abuse subtypes (sexual, physical, and emotional abuse; witnessing violence),
      three diagnostic screenings for borderline personality disorder (BPD), and self
      harm behavior. Psychiatric inpatients (N = 77) were evaluated for childhood abuse
      histories through a survey. Participants also underwent assessment for BPD using
      a self-report measure, clinical diagnosis, and a DSM-IV checklist. Finally, each
      was assessed for self-harm behavior using the 22-item Self-Harm Inventory (SHI).
      Compared with non-abused participants, those with abuse histories (with the
      exception of witnessing violence) had a significantly greater number of BPD
      confirmations (i.e., self-report, clinical diagnosis, DSM-IV checklist) as well
      as self-harm behaviors. When examining the total number of endorsed abuse
      subtypes, there was a significant correlation with the number of self-harm
      behaviors, but not the number of BPD diagnoses. Among psychiatric inpatients,
      childhood abuse demonstrates a complex relationship to BPD diagnoses and self
      harm behavior.

PMID- 11991157
TI  - Violence and gender: reports from an urban high school.
AB  - This article reports on the survey component of a study examining urban high
      school students' experiences with violence. The survey's purpose was to collect
      information on students' experiences with violence, explore gender differences,
      and identify which factors are associated with the self-reported use of violence.
      Two prominent risk factors for the self-reported use of violence were found:
      having a close friend or family member injured by violence, and gun possession.
      Young men and women did not differ significantly in overall exposure,
      victimization, and perpetration. However, gender clearly informed the types of
      violence reported. The findings offer practical strategies for addressing
      adolescent violence, such as reducing gun availability and community-level
      violence, but future research must further examine the role of gender in order to
      structure more effective prevention and intervention approaches that target
      different kinds of violence.

PMID- 11991158
TI  - Repeat rape and multiple offending among undetected rapists.
AB  - Pooling data from four samples in which 1,882 men were assessed for acts of
      interpersonal violence, we report on 120 men whose self-reported acts met legal
      definitions of rape or attempted rape, but who were never prosecuted by criminal
      justice authorities. A majority of these undetected rapists were repeat rapists,
      and a majority also committed other acts of interpersonal violence. The repeat
      rapists averaged 5.8 rapes each. The 120 rapists were responsible for 1,225
      separate acts of interpersonal violence, including rape, battery, and child
      physical and sexual abuse. These findings mirror those from studies of
      incarcerated sex offenders (Abel, Becker, Mittelman, Cunningham-Rathner, Rouleau,
      & Murphy, 1987; Weinrott and Saylor, 1991), indicating high rates of both repeat
      rape and multiple types of offending. Implications for the investigation and
      prosecution of this so-called "hidden" rape are discussed.

PMID- 11991159
TI  - The relationship between distress and resource loss following rape.
AB  - The present study examined the impact of resource loss on violent crime victims.
      Participants were 57 women who were recent victims of rape. Zero-order and point
      biserial correlations and multiple hierarchical regression results indicated that
      psychological distress was followed by increased resource loss for rape victims.
      These results suggest that distress may be an underlying mechanism for resource
      loss in victims of sexual assault.

PMID- 11991160
TI  - Perceived verbal conflict behaviors associated with physical aggression and
      sexual coercion in dating relationships: a gender-sensitive analysis.
AB  - We studied perceived partner verbal behaviors associated with participants' use
      of dating aggression. Men's reports of their partners' demanding, controlling,
      and psychologically abusive behaviors during conflicts were expected to predict
      men's perpetration against partners. In contrast, women's reports of their
      partners' withdrawal were expected to predict women's perpetration. Data were
      collected from heterosexual undergraduates (N = 223) in exclusive dating
      relationships. Participants' reports of partner demands and partner psychological
      abuse were associated with participants' use of physical aggression and sexual
      coercion. Reports of partner withdrawal and partner controlling behaviors were
      associated with participants' sexual coercion only. Significant moderating
      effects of gender emerged. As expected, partner demands, controlling behaviors,
      and psychological abuse were associated with physical aggression and sexual
      coercion in men, but not women. Partner withdrawal was associated with sexual
      coercion in both women and men. We conclude that gender-sensitive approaches are
      necessary to understand and prevent verbal conflict patterns associated with
      physical aggression and sexual coercion in intimate relationships.

PMID- 11991161
TI  - Synthesis and in vitro cytotoxic and antiviral activities of 1-(2,5,6-trideoxy-6
      halogenohept-5-enofuranurononitrile)thymine and derivatives.
AB  - All 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and their 3'
      O-TBDMS derivatives have been prepared and their configuration established. Some
      of these compounds are endowed with a cytotoxic or cytostatic activity in cell
      culture. The single most important factor affecting the cytotoxicity of these
      compounds is the presence on the molecule of a soft (electrofugal) halogen atom.

PMID- 11991162
TI  - Synthesis and biological evaluation of S-glycosylated pyridines.
AB  - The formation of thioglycosides 7a-j and 10a-j via the reaction of sodium salts
      of thiopyridines 3a-e with glycosyl bromides 6a,b has been studied. Comparison
      with the products obtained from silylated thiopyridines 8a-e and peracetylated
      sugars 9a,b is made. 13C NMR was utilized to elucidate the proposed structures of
      the products.

PMID- 11991163
TI  - 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine, a new prodrug of zidovudine.
      Synthesis, solid state characterization, and anti HIV-1 activity.
AB  - Synthesis, solid state characterization and anti HIV-1 activity of 3'-azido-3'
      deoxy-5'-O-isonicotinoylthymidine (2), a new prodrug of zidovudine (AZT, 1), are
      described. Two solid forms of 2 prepared by crystallization from ethyl acetate
      petroleum ether (form alpha) and from a melt sample of form alpha (amorphous
      form) were characterized by X-ray diffractometry, infrared spectroscopy,
      differential scanning calorimetry (DSC) and thermogravimetry (TGA) techniques.
      The novel nucleoside exhibited antiviral activity against standard and resistant
      strain panels of HIV-1 as well as cytotoxicity similar to that of AZT.

PMID- 11991164
TI  - Synthesis and in vitro antibacterial activity of novel 5'-O-analog derivatives of
      zidovudine as potential prodrugs.
AB  - An efficient, short synthesis of four potential prodrugs of 3'-azido-3'
      deoxythymidine (AZT) and their antibacterial activity are reported. The 5'-OH
      group of AZT was functionalized with oxalyl chloride obtaining an acyl chloride
      derivative (AZT-Ox), which by further transformation with leucine, isoleucine and
      valine amino acids led to the corresponding AZT analogs, namely AZT-Leu, AZT-iLeu
      and AZT-Val. A carboxyl acid derivative (AZT-Ac) was also obtained by hydrolysis
      of AZT-Ox. These compounds, which exhibit anti HIV activity, have killed
      collection and clinical strains of some opportunistic infectious agents in AIDS
      related complex. Thus, the clinical strains, K. oxytoca, S. typhi and K.
      pneumoniae, and collection strain K. pneumoniae ATCC 10031 showed sensitivity to
      antibiotics. The activity order for the studied compounds against the most
      sensitive strain (K. pneumoniae ATCC 10031) was AZT-Leu > AZT-iLeu > AZT-Val >
      AZT-Ac > AZT. On the other hand, the activity order for the second most sensitive
      strain (K. oxytoca) was AZT-Leu > AZT-Val = AZT-Ac > AZT-iLeu > AZT. The most
      effective antibacterial drug AZT-Leu, M.I.C.=0.125 microgmL(-1)) was 16 times
      more active than AZT (AZT, M.I.C.=2 microg mL(-1)) against K.

PMID- 11991165
TI  - Synthesis, antiviral and cytostatic activities, of carbocyclic nucleosides
      incorporating a modified cyclopentane ring. IV. Adenosine and uridine analogues.
AB  - Eight new carbocyclic nucleosides were prepared by mounting a purine (compounds 8
      10), 8-azapurine (12 and 13) or pyrimidine (15, 16 and 17b) on the amino group of
      (1S,3R)-3-aminomethyl-2,2,3-trimethylcyclopentylmethanol (6). All the compounds
      were evaluated as antiviral and antitumor agents in a variety of assay systems.
      Only compound 8 showed any cytostatic activity against the tumor cell lines
      examined.

PMID- 11991166
TI  - Synthesis and biological evaluation of isonucleosides derived from methyl 3,5
      anhydro-2-O-(2-fluorobenzyl)-D-xylofuranosides.
AB  - New isonucleosides [methyl 5-(1-pyrimidinyl)furanosides] are prepared by
      nucleophilic opening of the oxetane ring of methyl 3,5-anhydro-2-O-(2
      fluorobenzyl)-D-xylofuranoside with silylated pyrimidine bases in the presence of
      trimethylsilyl triflate. Structures, configurations and conformations were
      determined by NMR techniques and several X-ray diffraction analyses, seven of the
      isonucleosides were tested for cytotoxicity and activity against HIV, HSV and
      several other viruses.

PMID- 11991167
TI  - The postdoctoral fellowship.

PMID- 11991168
TI  - The Woodard and Sowell (2001) study adds to the body of nursing knowledge that
      supports spirituality as a concept that I believe is relevant to nursing
      practice.

PMID- 11991169
TI  - Nonfatal injury experiences among women on family farms.
AB  - Agricultural injury occurrence was determined among 1,096 working farm women in
      Texas and Louisiana. The 1-year cumulative incidence was 4.8%. Lower extremities
      were the body parts most frequently injured. The leading external causes were
      contact with foreign object, followed by falls and overdoing/ lifting. The
      seasonal pattern of injury was consistent with warm weather. The factors
      predictive of increased injury risk in multiple logistic regression included
      large animal farm type, greater time commitment, recurrent or persistent back
      conditions or weakness during the previous 12 months, hauling goods to market,
      and driving a tractor more than 52 days per year. Most women consulted a
      physician as a result of the injury. Resolving the problem of preventable farm
      related injuries will require a major and coordinated effort aimed not only at
      farm women themselves but also at multiple variables that profoundly affect the
      underlying conditions and behaviors that lead to farm-related injuries.

PMID- 11991170
TI  - Risk for acute confusion on hospital admission.
AB  - Elderly individuals are at risk for acute confusion (AC) during hospitalization.
      Using a prospective design, this study assessed the relationship between
      admission risk factors and subsequent development of AC in 117 elderly
      hospitalized patients. AC was ascertained using the NEECHAM Confusion Scale.
      Other measures included demographic data, cognitive status, physical function,
      laboratory data, medications, infections, activity, pain, and nursing acuity. The
      cumulative incidence estimate was 14%. Patients who developed AC were more likely
      to be admitted to the hospital from somewhere other than home, to have lower
      admission NEECHAM and MMSE scores, and to have restricted activity levels, an
      infection, and abnormal lab values. These patients were more cognitively and
      physically frail and may have been chronically undernourished and dehydrated on
      admission to the hospital. Nurses can be trained to routinely assess for acute
      confusion using easily implemented instruments incorporated into a research-based
      protocol.

PMID- 11991171
TI  - Screening and assessing adult asthmatics for anxiety disorders.
AB  - The purpose of this study was to evaluate a strategy designed to permit early
      detection of anxiety disorders in asthmatics. Ninety-one adult asthmatics were
      screened for anxiety disorders using the Sheehan Patient Rated Anxiety Scale
      (SPRAS) and the Anxiety Sensitivity Index (ASI) and then individually evaluated
      by a nurse trained in the administration of the Anxiety Disorders Interview
      Schedule-IV (ADIS-IV. Thirty-five (38%) of the participants met the diagnostic
      criteria for one or more anxiety disorders. Comparison of the SPRAS and ASI
      findings revealed that the SPRAS was more effective in detecting asthmatics
      likely to be suffering from coexisting anxiety disorders. Comparison of the
      nurses diagnostic formulations with those of an expert revealed that trained
      nurses using the ADIS-IV can diagnose anxiety disorders in the asthmatic
      population with a high degree of accuracy. These results have implications for
      resolving the problem of unrecognized and untreated anxiety disorders in the
      asthmatic population.

PMID- 11991172
TI  - Infant gender differences regarding acute established pain.
AB  - The purpose of this study was to ascertain if any gender differences existed in
      the behaviors of infants experiencing different levels of acute established pain
      and different levels of arousal within each level of pain. To do this, the
      behaviors of 152 two-week- to 12-month-old infants were videotaped and compared.
      Levels of pain were assessed by a panel of expert pediatric nurses. Results
      indicated that female 2-week- to 6-month-old infants performed more generally
      broadcast crying than did males and that the cries of female 7- to 12-month-old
      infants were of higher pitch than those of males. There was no gender difference
      in any facial or other bodily behavior. One cannot interpolate from these results
      that there are any gender differences in pain thresholds, only that there seem to
      be gender differences in behavioral responses to acute established pain.

PMID- 11991173
TI  - Use of protocols and guidelines by telephone nurses.
AB  - Changes in health care delivery, specifically the addition of telephone advice,
      affect how nurses work and how patients perceive care. It is important to
      understand the resources available to these nurses, the process by which they
      provide care, and patient outcomes. This descriptive study describes one type of
      resource, the availability and use of protocols. It also describes relationships
      between protocols and the quality of the nursing process and patient outcomes.
      Two-hundred-three taped calls to 32 advice RNs and 156 patient follow-up calls
      were used to measure protocol usage, nursing process quality, and patient
      outcomes. Although protocols were available for 78.8% of the calls, nurses varied
      in their extent of use (63.9% not fully used). There was a negative relationship
      (r = -0.395, p < 0.000) between the availability of protocols and overall quality
      of the nursing process. Protocol availability and use did not affect patient
      outcomes.

PMID- 11991174
TI  - Feasibility of in-home telehealth for conducting nursing research.
AB  - The purpose of this study was to determine the feasibility of using home audio/
      video telehealth equipment for administering nursing interventions to families,
      observing the client response, and collecting research data over specific
      intervals of time. The study design was a descriptive comparison with
      observational data collection. The subjects were adult patients (n = 5) using
      nighttime mechanical ventilators for obstructive sleep apnea and their home
      caregivers (n = 7). Skin color vital signs, spirometry, and pulse oximetry data
      collected simultaneously through telehealth equipment and through nurse
      observation in the home were the same. Care and the caregiver's use of the
      patient equipment were also observed. When nursing interventions, equipment
      demonstrations, visual illustrations, and audiotaped educational directions were
      used to facilitate patient care, they were transmitted across telehealth with a
      few exceptions. Costs of telehealth visits were less than traditional home
      visits, and client evaluations of telehealth were positive.

PMID- 11991175
TI  - Methods for biocatalyst screening.
AB  - Biocatalysts are now widely accepted as useful alternative tools to classic
      organic synthetic techniques for the regio- and enantioselective synthesis under
      mild reaction conditions in many fields of chemistry. The development of
      techniques for the rational or evolutionary design of novel or modified enzymes
      has increased the need for fast and reliable methods for the identification of
      the most powerful catalysts. We present a short overview on screening techniques
      in this area. Beside classical methods such as spectrophotometry and fluorimetry,
      a number of new approaches like methods based on the measurement of pH changes or
      IR-thermography have been recently developed. Additionally the use of
      electrospray and matrix-assisted laser desorption/ionization mass spectrometry
      has gained increasing influence in this field of biotechnology.

PMID- 11991176
TI  - Cultivation of hematopoietic stem and progenitor cells: biochemical engineering
      aspects.
AB  - The ex vivo expansion of hematopoietic cells is one of the most challenging
      fields in cell culture. This is a rapidly growing area of tissue engineering with
      many potential applications in bone marrow transplantation, transfusion medicine
      or gene therapy. Over the last few years much progress has been made in
      understanding hematopoietic differentiation, discovery of cytokines, isolation
      and identification of cellular subtypes and in the development of a variety of
      bioreactor concepts. All this has led to a number of (preliminary) clinical
      trials that gave a hint of the benefits that can be obtained from the use of
      expanded hematopoietic cells in therapy. Moreover, as we understand the
      complexity and the regulation of hematopoiesis, it becomes obvious that highly
      sophisticated cultivation techniques and bioreactor concepts are needed: a new
      challenge for bioprocess engineering in cell culture.

PMID- 11991177
TI  - Cell retention devices for suspended-cell perfusion cultures.
AB  - Perfusion cultures of animal cells have several advantages over batch or fed
      batch cultures. They give, for instance, higher productivities and a consistent
      product quality, and allow steady state operation and better cell physiology
      control. However, one of the main aspects limiting performance and scale-up of
      perfusion processes is the need for an adequate cell retention device. The
      devices currently in use for stirred perfusion bioreactors are continuous
      centrifuges, tangential flow membrane filters, dynamic filters, spin-filters,
      ultrasonic and dielectrophoretic separators, gravity settlers and, more recently,
      hydrocyclones. The advantages and disadvantages of each of these methods will be
      discussed.

PMID- 11991178
TI  - Fed-batch cultures of Escherichia coli cells with oxygen-dependent nar promoter
      systems.
AB  - The recombinant proteins produced from Escherichia coli as a host cell need to be
      made at as low a cost as possible because of the end of the monopoly following
      expiry of the patent on early pharmaceutical proteins, and thus expanding
      applications to non-pharmaceutical large-scale products. We review in this
      article how the various promoters used in recombinant E. coli could affect its
      protein products, especially with emphasis on relatively new oxygen-dependent nar
      promoters for beta-galactosidase production. Several studies carried out in the
      authors' laboratory show that the nar promoter does not require any chemicals
      except 1% nitrate and oxygen for protein production. And according to recent work
      with the modified strains it is possible to produce the enzyme (beta
      galactosidase) even without the nitrate ions at 45% of its total protein content
      when its cell density reached OD = 176.

PMID- 11991179
TI  - Production of core and virus-like particles with baculovirus infected insect
      cells.
AB  - In this paper the fundamental aspects of process development for the production
      of core and virus-like particles with baculovirus infected insect cells are
      reviewed. The issues addressed include: particle formation and monomer
      composition, chemical and physical conditions for optimal cell growth,
      baculovirus replication and product expression, multiplicity of infection
      strategy, and scale-up of the process. Study of the differences in the metabolic
      requirements of infected and non-infected cells is necessary for high cell
      density processes. In the bioreactor, the specific oxygen uptake rate (OURsp)
      plays a central role in process scale-up, leading to the specification of the
      bioreactor operational parameters. Shear stress can also be an important variable
      for bioreactor operation due to its influence on cell growth and product
      expression. The determination of the critical variables in process development is
      discussed, showing the relevance of the mathematical models that have been
      developed for the insect cells/baculovirus system in process implementation and
      control.

PMID- 11991180
TI  - Integrated approach to explore the potential of marine microorganisms for the
      production of bioactive metabolites.
AB  - During the last 10 years marine organisms have provided a large number of new
      natural products. Interesting compounds have mainly been derived from
      macroorganisms such as sponges, ascidians, corals and bryozoans. The number of
      secondary metabolites from marine microorganisms is smaller, but rapidly
      increasing. Because of the enormous difficulties involved in harvesting products
      from marine animals, and the fact that some of the bioactive compounds are
      produced by associated bacteria, the advantages of sustainable production of
      bioactive metabolites by bacteria or fungi, under the protection of natural
      resources, seem to be very attractive for the future. This review describes
      current progress in the isolation and identification of novel marine
      microorganisms, the discovery of new secondary metabolites, the biotechnological
      approaches to overproduce them, as well as the evaluation and characterization of
      their bioactivity.

PMID- 11991181
TI  - In-situ-fluorescence-probes: a useful tool for non-invasive bioprocess
      monitoring.
AB  - Optical sensors appear to be very promising for different applications in modern
      biotechnology. They offer the possibility to interface all the well known optical
      analysis techniques to bioprocesses via fiber optical cables. Thus, high
      sophisticated and sensitive optical analysis techniques can be coupled to a
      bioprocess via these light signal transporting fibers. A wide variety of sensor
      types for application in biotechnology has been described. Normally these sensors
      are non-invasive and the response times are nearly instantaneous. In particular,
      the use of glass fiber technology makes these sensors small, robust and reduces
      their costs.

PMID- 11991182
TI  - Bulk chemicals from biotechnology: the case of 1,3-propanediol production and the
      new trends.
AB  - The need for a sustainable resource supply, the rapid advances in plant
      biotechnology and microbial genetics and the strategic shift of major chemical
      companies into the area of life sciences are some of the driving forces for
      renewed interest in producing bulk chemicals from renewable resources by
      biological processes. The microbial production of 1,3-propanediol as briefly
      reviewed in this article and compared with the competing chemical processes
      demonstrates the promise and constraints of bioprocesses for bulk chemicals. The
      new concept of biorefinery and biocommodity engineering and future research needs
      in this area are also outlined.

PMID- 11991183
TI  - Metabolic flux analysis using mass spectrometry.
AB  - Detailed knowledge on carbon flux distributions is crucial for the understanding
      and targeted optimization of cellular systems. Analytical methods to identify the
      topology of metabolic networks and to quantify fluxes through its different
      pathways are therefore in the core of metabolic engineering. An elegant approach
      for metabolic flux analysis is provided by tracer experiments. In such studies
      tracer substrates with stable isotopes such as 13C are applied and the labeling
      pattern of metabolites is subsequently measured. Detailed flux distributions can
      be obtained by a combination of tracer experiments and stoichiometric balancing.
      In recent years, mass spectrometry (MS) has emerged as an interesting method for
      labeling measurements in metabolic flux analysis and provided valuable insights
      into the cellular metabolism. The present review provides an overview on current
      experimental and modeling tools for metabolic flux analysis by MS. The
      application of MS for flux analysis is illustrated by examples from the
      literature for various biological systems, including bacteria, fungi, tissue
      cultures and in vivo studies in humans.

PMID- 11991184
TI  - The molecular mechanism of ATP synthesis by F1F0-ATP synthase: a scrutiny of the
      major possibilities.
AB  - A critical goal of metabolism in living cells is the synthesis of adenosine
      triphosphate (ATP). ATP is synthesized by the enzyme F1F0-ATP synthase. This
      enzyme, the smallest-known molecular machine, couples proton translocation
      through its membrane-embedded, hydrophobic domain, F0, to the synthesis of ATP
      from adenosine diphosphate (ADP) and inorganic phosphate (Pi) in its soluble,
      hydrophilic headpiece, F1. Animals, plants and microorganisms all capture and
      utilize energy by this important chemical reaction. How does it occur? The
      binding change mechanism and the torsional mechanism of energy transduction and
      ATP synthesis are two mechanisms that have been proposed in the literature.
      According to the binding change mechanism (which considers reversible catalysis
      and site-site cooperativity), energy is required primarily for release of
      synthesized ATP, but not for its synthesis. On the other hand, according to the
      torsional mechanism (which considers an irreversible mode of catalysis and
      absence of cooperativity), all the elementary steps require energy, and the ion
      protein interaction energy obtained from the ion gradients is used to synthesize
      ATP, for Pi binding, and for straining the beta-epsilon bond in order to enable
      ADP to bind. The energy to release preformed ATP from the tight catalytic site
      (betaDP) is provided by the formation of the beta-epsilon ester linkage. First,
      the central features of these mechanisms are clearly delineated. Then, a critical
      scrutiny of these mechanisms is undertaken. The predictions of the torsional
      mechanism are listed. In particular, how the torsional mechanism deals with the
      specific difficulties associated with other mechanisms, and how it seeks to
      explain a wealth of structural, spectroscopic, and biochemical data is discussed
      in detail. Recent experimental data in support of the mechanism are presented.
      Finally, in view of the molecular machine nature of energy transduction, the
      indispensability of applying engineering tools at the molecular level is
      highlighted. This paves the way for the development of a new field: Molecular
      Physiological Engineering.

PMID- 11991185
TI  - Bioreactor developments for tissue engineering applications by the example of the
      bioartificial liver.
AB  - Tissue engineering is the application of the principles and methods of
      engineering and the life sciences towards the development of biological
      substitutes to restore, maintain or improve functions. It is an area which is
      emerging in importance worldwide. This article is to show the developments in
      tissue engineering research by the example of the bioartificial liver. As an
      alternative to liver transplantation, numerous researchers have been working
      towards the goal of development of a fully functional artificial liver. Liver
      support systems based on detoxification alone have proven ineffective because
      they cannot correct biochemical disorders. An effective artificial liver support
      system should be capable of carrying out the liver's essential processes, such as
      synthetic and metabolic functions, detoxification, and excretion. It should be
      capable of sustaining patients with fulminant hepatic failure and preparing
      patients for liver transplantation when a donor liver is not readily available.
      Although several hepatocyte-based liver support systems have been proposed, there
      is no current consensus on its eventual design configuration.

PMID- 11991186
TI  - A new coumaronochromone from Sophora japonica.
AB  - A new coumaronochromone derivative, sophorophenolone (1), along with 13 known
      compounds, l-maackiain (2), medicagol (3), 7-O-methylpseudobaptigenin (4),
      pseudobaptigenin (5), 7,3'-di-O-methylorobol (6), genistein (7), prunetin (8),
      daidzein (9), formononetin (10), Di-O-methyldaidzein (11), quercetin (12),
      kaempferol (13) and isorhamnetin (14) were isolated from pericarps of
      Sophorajaponica L. The structure of compound 1 was established by UV, IR, MS, and
      one-dimensional and two-dimensional NMR spectroscopy, including DEPT, NOESY, 1H
      1H COSY, HMQC, and HMBC experiments.

PMID- 11991187
TI  - A new flavone glycoside: 5,7,3',4'-tetrahydroxy-3-methoxy flavone-7-O-beta-D
      galactopyranosyl-(1-->4)-O-beta-D-glucopyranoside from the stem of Acacia catechu
      Willd.
AB  - A new bio-active flavone glycoside, m.p. C28H32O17, mp 283-284-C, M-640 [EIMS]
      was isolated from the ethylacetate soluble fraction of the ethanolic extract of
      the stems of Acacia catechu and its structure was characterised as 5,7,3',4'
      tetrahydroxy-3-methoxy flavone-7-O-beta-D-galactopyranosyl-(1-->4)-O-beta-D
      glucopyranoside by various chemical degradations and spectral analyses.

PMID- 11991188
TI  - Flavonol glycosides from Lysimachia capillipes.
AB  - Two new compounds, capilliposide I and capilliposide II, together with a known
      compound quercetin-3-O-(2,6-di-alpha-L-rhamnopyranosyl)-beta-D-galactopyranoside
      were isolated from the extracts of the whole herbs of Lysimachia capillipes.
      Their structures were established through their spectral data and chemical
      properties.

PMID- 11991189
TI  - Four new triterpenoid saponins from Ilex godajam.
AB  - Four new triterpenoid saponins, godosides A-D (1-4), along with eight known
      saponins, have been isolated from the fresh aerial parts of Ilex godajam.
      Structure elucidation of 1-4 was based on NMR, MS, IR and chemical analyses.

PMID- 11991190
TI  - Constituents from the roots of Heracleum rapula Franch.
AB  - A new coumarin glucoside, 8-hydroxy-5-O-beta-D-glucosylpsoralen, along with 17
      known coumarins and one steroid, was isolated from the roots of Heracleum rapula
      Franch. Four coumarin glucosides, including the new one, were obtained from the
      water-soluble fraction. The other coumarins isolated from the ethyl acetate
      fraction included 10 furanocoumarins, a simple coumarin and three types of
      bicoumarins. Their structures were elucidated by means of spectroscopic analysis.

PMID- 11991191
TI  - Phenolic glucosides from Oxytropis myriophylla.
AB  - Three phenolic glucosides were isolated from Oxytropis myriophylla. On the basis
      of spectral analyses, their structures were elucidated as 2-methoxy-4-(3'-hydroxy
      n-butyl)-phenol-1-O-beta-D-glucopyranoside (1), syringin (2), 2-methoxy-4-(3'
      hydroxy-propenyl)-phenol-1-O-beta-D-glucopyranoside (3). Compound (1) is a new
      phenolic glucoside named myriophylloside A, the other two compounds are isolated
      from this plant for the first time.

PMID- 11991192
TI  - Phenolic glucosides from Alangium plantanifolium.
AB  - A novel phenolic glucoside alangitanifoliside A (1) together with two known
      phenolic glucosides 4',6'-O-(S)-hexahydroxydiphenylsalicin (2) and salicin (3),
      and gallic acid were isolated from stem barks of Alangium plantanifolium. Their
      structures were determined by spectroscopic and chemical methods. The structure
      of 1 was elucidated to be 1-O-[2-(1-hydroxy-6-oxocyclohex-2-ene-1-carboxymethyl)
      phenyl]-4,6-O-[(S)-,4,4',5,5' 6,6'-hexahydroxydiphenoyl]-beta-D-glucopyranose.

PMID- 11991193
TI  - New beyerane and isopimarane diterpenoids from Rhizophora mucronata.
AB  - Chemical examination of the ethyl acetate extract of the roots of Rhizophora
      mucronata collected from Mangalore Coast resulted in the isolation of three more
      new diterpenoids, rhizophorins C-E (1-3) in addition to the two, rhizophorin A,
      (6R,11S,13S)-6,11,13-trihydroxy-2,3-seco-14-labden-2,8-olid-3-oic acid, and
      rhizophorin B, ent-3beta,20-epoxy-3alpha,18-dihydroxy-15-beyerene, recently
      reported. The structures of the new diterpenoids have been elucidated by a study
      of their physical and spectral data as 17-hydroxybeyer-15-en-3-one (1), 3beta,17
      diacetoxy-15-beyeren-2-one (2) and 3beta,6alpha-diacetoxy-8(14),15-isopimaradien
      2-one (3).

PMID- 11991194
TI  - High yield formation of o-aminobenzoic acid-7-O-beta-D-(beta-1,6-O-d
      glucopyranosyl)-glucopyranosyl ester in cell suspension cultures of Solanum
      mammosum.
AB  - Cell suspension cultures of Solanum mammosum cultivated in modified Murashige &
      Skoog media could synthesize o-aminobenzoic acid-7-O-beta-D-(beta-1,6-O-D
      glucopyranosyl)-glucopyranosyl ester from o-amino benzoic acid with a yield of
      about 20% dry weight in 7 days. The maximum production of o-aminobenzoic acid-7-O
      beta-D-(beta-1,6-O-D-glucopyranosyl)-glucopyranosyl ester was 31.8% on dry weight
      basis.

PMID- 11991195
TI  - A new phytosterone from Cyanotis arachnoidea.
AB  - From Cyanotis arachnoidea C.B. Clarke, a new phytosterone named cyanosterone A
      (1), along with three known compounds--beta-ecdysone (2), ajugasterone C (3) and
      beta-sitosterol (4) were isolated. The structure of the new compound was
      determined as 3beta,14alpha,20R,22R-tetrahydroxy-5alpha-cholest-7-en-6-one on the
      basis of physicochemical properties and spectral analysis.

PMID- 11991196
TI  - A new compound from Gastrodia elata Blume.
AB  - A new compound, alpha-acetylamino-phenylprophyl alpha-benzoylamino
      phenylpropionate (1) and a known compound 4-hydroxybenzyl beta-sitosterol ether
      (2), were isolated from the tubers of Gastrodia elata Blume and their structures
      were elucidated by spectral data.

PMID- 11991197
TI  - The independence of signaling pathways mediating increased expression of
      plasminogen activator inhibitor type 1 in HepG2 cells exposed to free fatty acids
      or triglycerides.
AB  - We have shown that both free fatty acids (FFA) and triglycerides (TG) increase
      expression of plasminogen activator inhibitor type 1 (PAI-1) in vivo and in
      vitro. To determine signaling mechanisms responsible, HepG2 cells were exposed to
      FFA, emulsified TG, or the combination. The combination of FFA and TG increased
      PAI-1 to a greater extent than either agent alone (fold induction: 0.45mM FFA 1.7
      +/- 0.2, 1,000 mg/dl TG 1.9 +/- 0.1, both 2.3 +/- 0.2, n=10, p<0.05 for
      comparison of combination with either alone). Cells transfected with PAI-1 5'
      flanking region containing the 4G or 5G polymorphism displayed similar activity
      in response to FFA, but modestly greater activity with the 4G polymorphism in
      response to TG (fold induction: 5G-1.28 +/- 0.14 and 4G-1.46 +/- 0.13, n=6, p <
      0.05 for comparison). Deletion analyses demonstrated that FFA and TG induce PAI-1
      expression through distinct regions of the promoter. Inhibition of protein kinase
      C inhibited the response to FFA but not TG. Accordingly, increased FFA and TG
      contribute to increased PAI-1 through independent mechanisms.

PMID- 11991198
TI  - Hydrogen peroxide-induced inhibition of vasomotor activity: evaluation of single
      and combined treatments with vitamin A and insulin in streptozotocin-diabetic
      rats.
AB  - A positive correlation has been established between increased oxidative stress
      and cardiovascular diseases in diabetes mellitus. We evaluated the effects of
      single or combined treatments with vitamin A (retinol acetate, 30 mg/kg/day, for
      12-weeks) and insulin (8-10 IU/rat/day for the final 6-week) on vasomotor
      activity, oxidative stress and retinol metabolism in 12-week streptozotocin
      diabetic rats. The vasomotor activity was determined by measuring in vitro
      responsiveness of aorta rings to phenylephrine (PE) and acetylcholine (ACh) in
      the absence or in the presence of hydrogen peroxide (H2O2). Preincubation with
      H2O2 (10 microM) produced a significant decrease in PE (1 mM)-induced contraction
      in untreated-diabetic but not in control rats. Single treatment with insulin
      counteracted this effect of H2O2 and also reversed the increased contractile
      response of diabetic aorta to PE, while vitamin A was found to be ineffective.
      H2O2 (10 microM) also inhibited ACh (1 mM)-stimulated endothelium-dependent
      relaxation two fold more in diabetic than in control aorta. In the prevention of
      H2O2-induced inhibition of vascular relaxation to ACh, vitamin A alone was
      markedly effective while insulin alone was not. The combination of vitamin A plus
      insulin removed the inhibitory action of H2O2 in diabetic aorta. Diabetic animals
      displayed an increased level of aorta thiobarbituric acid reactive substance
      (TBARS) in association with decreased levels of plasma retinol and retinol
      binding protein (RBP). Single treatment with insulin, in spite of allowing
      recovery of normal growth rate and improved glucose and retinol metabolism in
      diabetic rats, was unable to control TBARS production to the same extent as
      vitamin A alone. Our findings suggest that the maintenance of ACh-stimulated
      endothelium-dependent vasorelaxant tone in normal physiological levels depends
      largely on the prevention and/or inhibition of peroxidative stress, which is
      achieved by combined treatment with vitamin A plus insulin. The use of vitamin A
      together with insulin provides a better metabolic control and more benefits than
      use of insulin alone in the reduction of diabetes-induced vascular complications.

PMID- 11991199
TI  - Potentiation of mitogenic activity of platelet-derived growth factor by
      physiological concentrations of insulin via the MAP kinase cascade in rat A10
      vascular smooth muscle cells.
AB  - Hyperinsulinemia has been shown to be associated with diabetic angiopathy.
      Migration and proliferation of vascular smooth muscle cells (VSMC) are the
      processes required for the development of atherosclerosis. In this study, we
      attempted to determine whether insulin affects mitogenic signaling induced by
      platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells). PDGF
      stimulated DNA synthesis which was totally dependent on Ras, because transfection
      of dominant negative Ras resulted in complete loss of PDGF-stimulated DNA
      synthesis. Initiation of DNA synthesis was preceded by activation of Raf-1, MEK
      and MAP kinases (Erk 1 and Erk2). Treatment of the cells with PD98059, an
      inhibitor of MAPK kinase (MEK) attenuated but did not abolish PDGF-stimulated DNA
      synthesis, suggesting that MAPK is required but not essential for DNA synthesis.
      PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70
      S6Kinase (p70S6K) in a wortmannin-sensitive manner. Rapamycin, an inhibitor of
      p70S6K, markedly suppressed DNA synthesis. Low concentrations of insulin (1-10
      nmol/l) alone showed little mitogenic activity and no significant effect on MAPK
      activity. However, the presence of insulin enhanced both DNA synthesis and MAPK
      activation by PDGF. The enhancing effect of insulin was not seen in cells treated
      with PD98059. Insulin was without effect on PDGF-stimulated activations of
      protein kinase B (Akt/PKB) and p70S6K. We conclude that insulin, at
      pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA
      synthesis, at least in part, by potentiating activation of the MAPK cascade.
      These results are consistent with the notion that hyperinsulinemia is a risk
      factor for the development of atherosclerosis.

PMID- 11991200
TI  - Effects of aminoguanidine on lipid and protein oxidation in diabetic rat kidneys.
AB  - Nonenzymatic glycation of tissue and plasma proteins may stimulate the production
      of oxidant and carbonyl stress in diabetes. The aim of this study was to evaluate
      the effects of aminoguanidine (AG) on lipid peroxidation, protein oxidation and
      nitric oxide (NO) release in diabetic rat kidneys. After induction of diabetes
      with streptozotocin, female Wistar rats were divided into 2 groups. Group DAG
      (n=9) rats were given AG hydrogen carbonate (1 g/L) in drinking water and group D
      (n=8) was diabetic control rats given only tap water. Group H (n=8) was followed
      as healthy controls. At the end of an 8 week period, NO release, lipid and
      protein oxidation were determined in kidney tissues. NO release was significantly
      lower in diabetic rats compared with healthy controls (p<0.05). Lipid
      peroxidation was significantly high in group D (3.9 +/- 0.3 nmol MDA/g tissue)
      compared with the group DAG (2.6 0.1 nmol MDA/g tissue, p<0.01) and group H (2.4
      +/- 0.2 nmol MDA/g tissue). Protein oxidation was significantly higher in
      diabetics than healthy controls (563.8 +/- 23.9, 655.8 +/- 7.2, 431.5 +/- 8.8
      mmol carbonyl / g tissue for group DAG, D and H, respectively, p< 0.05). A
      positive correlation between albuminuria and thiobarbituric acid reactive
      substance (TBARS) levels (r= 0.54,p<0.005) and carbonyl content (r=0.70,
      p<0.0005) in kidney homogenate were observed. Although AG treatment had no effect
      on NO release, it significantly decreased lipid peroxidation in diabetic rat
      cortices. Consequently increased lipid peroxidation -as well as- protein
      oxidation could be involved in the pathogenesis of diabetic albuminuria.

PMID- 11991201
TI  - Pancreatic beta-cell death, regeneration and insulin secretion: roles of poly(ADP
      ribose) polymerase and cyclic ADP-ribose.
AB  - In the early 1980s, we proposed a unifying model for beta-cell damage (The
      OKAMOTO model), in which poly(ADP-ribose) synthetase/polymerase (PARP) activation
      plays an essential role in the consumption of NAD+, which leads to energy
      depletion and necrotic cell death. In 1984, we demonstrated that the
      administration of PARP inhibitors to 90% depancreatized rats induces islet
      regeneration. From the regenerating islet-derived cDNA library we isolated Reg
      (Regenerating Gene) and demonstrated that Reg protein induces beta-cell
      replication via the Reg receptor and ameliorates experimental diabetes. More
      recently, we showed that the combined addition of IL-6 and dexamethasone induces
      the Reg gene expression in beta-cells and that PARP inhibitors enhance the
      expression. In 1993, we found that cyclic ADP-ribose (cADPR), a product
      synthesized from NAD+, is a second messenger for intracellular Ca2+ mobilization
      for insulin secretion by glucose, and proposed a novel mechanism of insulin
      secretion, the CD38-cADPR signal system. Therefore, PARP inhibitors prevent beta
      cell necrosis, induce beta-cell replication and maintain insulin secretion.

PMID- 11991202
TI  - Renal AT1 receptor protein expression during the early stage of diabetes
      mellitus.
AB  - Experiments were performed to evaluate the hypothesis that the early stage of
      Type 1 diabetes mellitus (DM) increases renal angiotensin II (AngII)
      concentration and angiotensin type 1 (AT) receptor protein levels. Nineteen or
      twenty days after vehicle (Sham rats) or streptozotocin (STZ rats) treatment,
      plasma [AngII] was higher in STZ rats (152 +/- 23 fmol/ml) than in Sham rats (101
      +/- 7 fmol/ml); however, kidney [AngII] did not differ between groups. AT1
      receptor protein expression was greater in STZ kidneys than in Sham kidneys. This
      increase was restricted to the cortex, where AT1 protein levels were elevated by
      77 +/- 26% (42 kDa) and 101 +/- 16% (58 kDa) in STZ kidneys. Immunohistochemistry
      revealed this effect to be most evident in distal nephron segments including the
      connecting tubule/cortical collecting duct. Increased renal cortical AT1 receptor
      protein and circulating AngII levels are consistent with an exaggerated AngII
      dependent influence on renal function during the early stage of DM in the rat.

PMID- 11991203
TI  - A 27-mer tandem repeat polypeptide in bovine amelogenin: synthesis and CD
      spectra.
AB  - CD spectra of a tandem 27-mer repeat polypeptide, Gln-Pro-His-Gln-Pro-Leu-Gln-Pro
      His-Gln-Pro-Leu-Gln-Pro-Met-(Gln-Pro-Leu)4, from bovine amelogenin synthesized by
      standard solid-phase synthesis manifests an archtypical CD pattern of a beta
      spiral structure in phosphate buffer at pH 5.2 and trifluoroethanol (TFE), CF3OH.
      beta-spiral structure is unique to a class of diverse proteins including
      amelogenins conferring unusual physicochemical properties.

PMID- 11991204
TI  - Identification of single amino acid residues essential for the binding of
      lipopolysaccharide (LPS) to LPS binding protein (LBP) residues 86-99 by using an
      Ala-scanning library.
AB  - Lipopolysaccharide binding protein (LBP) is a 60 kDa acute phase glycoprotein
      capable of binding to LPS of Gram-negative bacteria and facilitating its
      interaction with cellular receptors. This process is thought to be of great
      importance in systemic inflammatory reactions such as septic shock. A peptide
      corresponding to residues 86-99 of human LBP (LBP86-99) has been reported to bind
      specifically with high affinity the lipid A moiety of LPS and to inhibit the
      interaction of LPS with LBP. We identified essential amino acids in LBP86-99 for
      binding to LPS by using a peptide library corresponding to the Ala-scanning of
      human LBP residues 86-99. Amino acids Trp91 and Lys92 were indispensable for
      peptide-LPS interaction and inhibition of LBP-LPS binding. In addition, several
      alanine-substituted synthetic LBP-derived peptides inhibited LPS-LBP interaction.
      Substitution of amino acids Arg94, Lys95 and Phe98 by Ala increased the
      inhibitory effect. The mutant Lys95 was the most active in blocking LPS binding
      to LBP. These findings emphasize the importance of single amino acids in the LPS
      binding capacity of small peptides and may contribute to the development of new
      drugs for use in the treatment of Gram-negative bacterial sepsis.

PMID- 11991205
TI  - Investigation of penetratin peptides. Part 1. The environment dependent
      conformational properties of penetratin and two of its derivatives.
AB  - The homeodomain, the DNA-binding domain of Antennapedia homeoprotein, is composed
      of three alpha-helices and one beta-turn between helices II and III. Its third
      helix from the N-terminal (helix III) can translocate through the cell membrane
      into the nucleus and can be used as an intracellular vehicle for the delivery of
      oligopeptides and oligonucleotides. To the best of our knowledge, this helix III,
      called penetratin, which consists of 16 amino acids, is internalized by cells in
      a specific, non-receptor-mediated manner. For a better understanding of the
      mechanism of the transfer, the structure of penetratin was examined in both
      extracellular matrix-mimetic and membrane-mimetic environments: 1H-NMR and CD
      spectroscopic measurements were performed in mixtures of TFE/water with different
      ratios. The molecular conformations of two analogue peptides [(6,14-Phe)
      penetratin and a 12 amino acid penetratin derivative (peptide 3)] were also
      studied. An atomic level comprehensive analysis of penetratin and its two
      analogues was performed. In a membrane-mimetic solvent system (TFEd2/water = 9:
      1), on the basis of 553 distance restraints, the 4-12 region of penetratin
      exhibits a bent, irregular helical structure on NMR examination. Interactions
      between hydrophobic amino acid residues in conjunction with H-bonds stabilize the
      secondary structure of the molecule. Thus, both derivatives adopt a helix-like
      conformation. However, while (6,14-Phe)-penetratin displays both alpha-helical
      and 310-helical features, the structure of peptide 3 is predominantly a 310
      helix. Of the three peptides, surprisingly (6,14-Phe)-penetratin has the largest
      helical content. An increase in the polarity of the molecular environment
      gradually disintegrates these helix-like secondary structures. In a highly
      aqueous molecular system (TFEd2/water = 1 : 9), the fast exchange of multiple
      conformers leads to too few distance restraints being extracted, therefore the
      NMR structures can no longer be determined. The NMR data show that only short
      range order can be traced in these peptides. Under these conditions, the
      molecules adopt nascent helix-like structures. On the other hand, CD spectra
      could be recorded at any TFE/water ratio and the conformational interconversion
      could therefore be monitored as a function of the polarity of the molecular
      environment. The CD data were analysed comprehensively by the quantitative
      deconvolution method (CCA+). All three penetratin peptides display helical
      conformational features in a low dielectric medium, with significant differences
      as a function of their amino acid composition. However, these conformational
      features are gradually lost during the shift from an apolar to a polar molecular
      environment.

PMID- 11991206
TI  - Synthesis of a membrane protein with two transmembrane regions.
AB  - A membrane protein with two transmembrane domains was synthesized by means of the
      thioester method. The F1F0 ATP synthase subunit c (Sub.c), which consists of 79
      amino acid residues (MW 8257), was chosen as a target. For synthetic purposes,
      two building blocks, Boc-[Lys34(Boc)]-Sub.c(1-38)-SCH2CH2CO-Ala and Sub.c(39-79),
      were synthesized via solid-phase methods using Boc chemistry. RP-HPLC
      purification conditions for the transmembrane peptide were examined. As a result,
      a combination of a mixture of formic acid, 1-propanol and water with a phenyl
      column was found to be useful for separating the transmembrane peptide. The
      purified building blocks were condensed in DMSO in the presence of silver
      chloride, 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (HOOBt), N,N
      diisopropylethylamine to give the product, Sub.c, after removal of Boc groups
      (yield 16%). The yield of the condensation reaction could be improved to 23% by
      raising the reaction temperature to 50 degrees C, and to 26% when a mixture of
      chloroform and methanol was used as a solvent.

PMID- 11991207
TI  - Measurement of stress effects (scope for growth) and contaminant levels in
      mussels (Mytilus edulis) collected from the Irish Sea.
AB  - The objective of this research was to quantify the impact of pollution along the
      coastlines of the Irish Sea. Pollution assessment was based on the combined
      measurement of scope for growth (SFG), and chemical contaminants in the tissues
      of mussels (Mytilus edulis) collected from 38 coastal sites around the Irish Sea
      during June-July in 1996 and 1997. On the UK mainland coast, the SFG showed a
      general trend with a significant decline in water quality in the Liverpool and
      Morecambe Bay region. High water quality was recorded along the west coast of
      Wales, as well as southwest England and northwest Scotland (clean reference sites
      outside the Irish Sea). Along the coast of Ireland there was a similar trend with
      reduced SFG within the Irish Sea region. SFG was generally low north of Duncannon
      and then improved north of Belfast. The poor water quality on both sides of the
      Irish Sea is consistent with the prevailing hydrodynamics and the spatial
      distribution of contaminants associated with urban/ industrial development. The
      decline in SFG of mussels on both sides of the Irish Sea was associated with a
      general increase in contaminant levels in the mussels. Certain contaminants,
      including PAHs, TBT, sigmaDDT, Dieldrin, gamma-HCH, PCBs, and a few of the metals
      (Cd, Se, Ag, Pb), showed elevated concentrations. Many of these contaminants were
      particularly elevated in the coastal margins of Liverpool Bay, Morecambe Bay and
      Dublin Bay. A quantitative toxicological interpretation (QTI) of the combined
      tissue residue chemistry and SFG measurements indicated that at the majority of
      coastal sites, c. 50 to > 80% of the observed decline in SFG was due to PAHs as a
      result of fossil fuel combustion and oil spills. TBT levels were highest at major
      ports and harbours, but these concentrations only made a minor contribution to
      the overall reduction in SFG. At no sites were individual metals accumulated to
      concentrations that could cause a significant effect on SFG. The study identified
      many sites where the observed reduction in SFG was far greater than predicted
      from the limited number of chemical contaminants analysed, thus indicating the
      presence of additional 'unknown toxicants'. Sewage (containing domestic,
      agricultural and industrial components) appears to be an important contributor to
      reduced SFG and linear alkylbenzenes (LABs) and As may provide suitable 'sewage
      markers'. There was a highly significant positive correlation between SFG and As
      (P < 0.001). This relationship may be due to reduced As uptake by algal food
      material and mussels at sites with elevated P04 concentrations (e.g. at sites
      with sewage inputs). Phosphate is a known competitive inhibitor of As
      accumulation, at least in algae. The results highlight that further research is
      required on 'sewage markers' in mussels. The SFG approach therefore provides a
      rapid, cost-effective and quantitative measure of pollution impact, as well as a
      means of identifying the causes through a QTI of tissue contaminants levels. It
      also serves to identify the presence of unidentified toxicants and areas that
      require further study.

PMID- 11991208
TI  - Distribution of PACs in surficial sediments and bioavailability to mussels,
      Mytilus edulis of Halifax Harbour.
AB  - Surficial sediments and blue mussels were collected around the perimeter of
      Halifax Harbour. Samples were analysed for the levels and fingerprint of
      polycyclic aromatic compounds (PACs). The objective was to explore the
      relationship between contaminant profiles in sediments and in mussels and to
      explore the possibility of deducing their sources, pattern of deposition and
      circulation in the harbour. Combustion derived compounds predominated in both
      sets of samples, with more variability observed in the level of petroleum derived
      hydrocarbons in mussel samples. Biota-sediment accumulation factors (BSAF,
      dry/dry wt.) varied throughout the harbour, ranging from means of 0.006 to 1.26,
      where generally fluoranthene displayed the highest BSAF. Sediments and mussels
      give complementary views of the geographical distribution of contaminants, they
      reflect the state of benthic and pelagic habitats. Results observed for Halifax
      Harbour are discussed from the perspective of published data.

PMID- 11991209
TI  - The influence of long emersion on biota, ammonium fluxes and nitrification in
      intertidal sediments of Marennes-Oleron Bay, France.
AB  - A comparative study between waterlogged and reflooded intertidal sediments was
      undertaken in March and June 1999 through statistical analysis of selected
      sediment parameters (biota, salinity, O2, Eh), pool sizes and benthic fluxes of
      nutrients (NH4+, NO2-, NO3-) and nitrification rates. In March samples, absence
      of polychaetes and oligochaetes from upper sediment horizons were due to
      erosional events sweeping away surface sediments. Presence of richer annelid
      assemblages in June samples indicated more stable hydrodynamic conditions that
      favoured the development of benthic microalgae biofilms. Dewatering of sediments
      during a 3-day emersion period promoted a salinity rise on top layers, migration
      of pore water ions towards the sediment surface, and created sediment fissures
      that accelerated water exchange on reflooding. Reflooded and waterlogged sediment
      systems were comparable with respect to the release of NH4+ to overlying water
      but were different with respect to nitrification rates. Sediment-water NH4+
      fluxes were higher (P = 0.011) in March (3.3 mmol m(-2) day(-1) compared to June
      (1.4 mmol m(-2) day(-1) due to higher macrofauna biomasses and lower benthic
      microalgae concentrations in March samples. Potential nitrification rates (range
      from 19 to 60 mmol NO3- (-2) day(-1)) were not statistically different between
      March and June. A thinner oxic layer in reflooded compared with waterlogged
      systems reflects a decrease of O2 diffusion into sediment at high salinities
      which resulted in the fall of the actual nitrification rates (P < 0.05). Our data
      suggest that long term dessication of intertidal sediments may depress the
      nitrification process at the ecosystem level.

PMID- 11991210
TI  - Seasonal factors affecting surfactant biodegradation in Antarctic coastal waters:
      comparison of a polluted and pristine site.
AB  - This report is the first seasonal study of anthropogenic pollutant biodegradation
      rates in Antarctic coastal waters. The capacity of surface waters from Rothera
      Research Station, Adelaide Island, Antarctica, to biodegrade the anionic
      surfactant sodium dodecyl sulphate (SDS) was quantified in biodegradation tests
      from April 1988 to January 1999. Large temporal differences in the persistence of
      SDS were observed. In mid-winter (July), the SDS-biodegradation half life was
      twice that measured in mid-summer (January), despite small temperature
      differences (up to 2.45 degrees C). Comparisons between water from a pristine
      site and a site receiving grey-waste water from the station showed that some
      acclimation to SDS was occurring in the contaminated water. This resulted in SDS
      half lives up to to approximately 80 h shorter in the polluted water compared
      with the pristine site in the summer months when a large population of SDS
      degrading bacteria had developed. Biodegradation half lives in Antarctic coastal
      waters (160-460 h) were generally far higher than those observed in temperate
      waters.

PMID- 11991211
TI  - The utility of the terms "bioavailability" and "bioavailable fraction" for
      metals.
AB  - Because concentrations of total or dissolved metal usually are not good
      predictors of the acute toxicity of metals to aquatic biota (i.e. not all of the
      metal appears to be bioavailable), it has been tempting for researchers and
      regulators to attempt to identify a form or combination of forms of a metal that
      is the bioavailable fraction. But from geochemical, biological, and analytical
      perspectives, the term ''bioavailable fraction" is context-specific (i.e. not
      generalizable) and quantitatively elusive. Although the term "bioavailability"
      conveys a useful, general concept and should be retained in the aquatic
      toxicology lexicon, the term "bioavailable fraction" should be avoided.

PMID- 11991212
TI  - A link between polymorphonuclear leukocyte intracellular calcium, plasma insulin,
      and essential hypertension.
AB  - BACKGROUND: Intracellular ionized calcium ([Ca2+]i) is a key mediator in the
      activation and oxidant production by peripheral polymorphonuclear leukocytes
      (PMN). Primed PMN contribute to oxidative stress (OS) and inflammation in
      essential hypertension (EH). Elevated [Ca2+]i has been described in insulin
      resistant states and in various cell types in EH but not in EH PMN. The aim of
      this study was to evaluate the levels of [Ca2+]i in peripheral EH PMN in relation
      to plasma insulin levels and blood pressure (BP). METHODS: The PMN were separated
      from blood of 20 nonsmoking, nonobese untreated EH patients, age range 20 to 60
      years and from 20 age- and gender-matched healthy individuals (NC). Plasma
      glucose and insulin levels 2 h after a 75-g oral glucose load, reflected insulin
      resistance. PMN [Ca2+]i was measured by flow cytometry in isolated cells stained
      with Fluo-3. RESULTS: The EH PMNs showed significantly increased [Ca2+]i compared
      to NC PMN. Eighty percent of EH patients showed significantly higher plasma
      insulin levels after glucose load. Linear regression analysis showed significant
      correlation between 1) PMN [Ca2+]i and mean arterial pressure (MAP) (r = 0.5, P <
      .006); 2) PMN [Ca2+]i and fasting plasma insulin (r = 0.7, P < .005); and 3)
      fasting plasma insulin and MAP (r = 0.4, P < .04). CONCLUSIONS: This study adds
      PMN to previously described cells exhibiting elevated [Ca2+]i, contributing to OS
      and inflammation. The correlation of individual BP with both PMN [Ca2+]i and
      plasma insulin levels, together with the fact that elevated [Ca2+]i mediates PMN
      priming, suggest that elevated [Ca2+]i and insulin are involved in the
      pathogenesis of hypertension-induced vascular injury in EH.

PMID- 11991213
TI  - Decreased erythrocyte insulin binding in hypertensive subjects with
      hyperinsulinemia.
AB  - BACKGROUND: This study investigates erythrocyte insulin receptor binding and
      affinity in subjects with hypertension and hyperinsulinemia. Insulin receptor
      binding function has not been extensively studied in hypertensive subjects.
      METHODS: Insulin receptor density, binding affinity, and protein tyrosine kinase
      activity were measured in erythrocytes from 18 hypertensive and 16 normotensive
      subjects. Insulin sensitivity was measured by the fasting plasma insulin/glucose
      ratio and the homeostatic assessment model algorithm (HOMA) index. Erythrocyte
      insulin binding was determined by a competitive binding assay and protein
      tyrosine kinase activity was measured by an enzyme-linked immunoabsorbent assay
      technique. RESULTS: Fasting plasma insulin/glucose ratio and the insulin
      resistance index (HOMA) were significantly higher in the hypertensive versus
      normotensive subjects. Receptor saturation of the high affinity binding sites
      (Bmax) was reduced in the hypertensive versus control subjects. The Kd values
      were lower in the erythrocytes from hypertensive than control subjects. Insulin
      induced protein tyrosine kinase activity was decreased in erythrocytes from
      hypertensive versus control subjects. CONCLUSIONS: A reduced erythrocyte insulin
      receptor density and tyrosine protein kinase activity may reflect insulin
      receptor dysfunction in hypertensive individuals who have insulin resistance and
      hyperinsulinemia. More information is needed examining insulin receptor function
      in other target tissues such as fat or skeletal muscle cells before defects in
      the insulin receptor can be firmly proposed as a cause of the metabolic syndrome.

PMID- 11991214
TI  - A low-calorie diet improves endothelium-dependent vasodilation in obese patients
      with essential hypertension.
AB  - BACKGROUND: Both obesity and hypertension are associated with endothelial
      dysfunction. The purpose of this study was to investigate the effects of a low
      calorie diet on endothelial function in obese patients with essential
      hypertension. METHODS: We measured forearm blood flow (FBF) during intra-arterial
      infusion of acetylcholine (ACh; 7.5, 15, 30 microg/min), an index of endothelium
      dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0
      microg/min), an index of endothelium-independent vasodilation, in obese patients
      with essential hypertension before and after 2 weeks on a low-calorie diet (800
      kcal/d). The study included 11 obese hypertensive Japanese patients (mean body
      mass index, 30.8 +/- 3.6 kg/m2). Fifteen healthy Japanese normotensive
      individuals were recruited as a control group. RESULTS: In obese patients with
      hypertension, the response of FBF to ACh was attenuated compared to healthy
      individuals (P < .001). Caloric restriction reduced body weight from 77.5 +/-
      15.0 to 73.2 +/- 13.5 kg (P < .01), the mean blood pressure from 118.4 +/- 8.7 to
      105.7 +/- 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 +/- 22.8 to 64.8
      +/- 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 +/- 0.76 to 4.67 +/-
      0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 +/- 0.48
      to 3.29 +/- 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight
      reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but
      did not alter the response to ISDN. The intra-arterial infusion of NG-monomethyl
      L-arginine (8 micromol/min), a nitric oxide synthase inhibitor, decreased the
      enhanced ACh-induced blood flow response induced by caloric restriction.
      CONCLUSIONS: The present findings suggest that the caloric restriction improves
      endothelial-dependent vasodilation through an increased release of nitric oxide
      in obese hypertensive patients.

PMID- 11991215
TI  - Normal perivascular sensory dilator nerve function in arteries of Zucker diabetic
      fatty rats.
AB  - BACKGROUND: Type II diabetes in humans is associated with pathology of both the
      cardiovascular and peripheral sensory nervous systems. Because abnormal
      vasodilator responses have been reported in animals of type II diabetes and
      perivascular sensory nerves are a source of vasodilator substances, we tested the
      hypothesis that sensory nerve-dependent relaxation is abnormal in arteries of the
      Zucker diabetic fatty (ZDF) rat model of type II diabetes. METHODS: The ZDF rats
      and genetic controls were studied at 26 weeks of age. Tail-cuff systolic blood
      pressure (BP) was measured, serum was obtained for chemical determinations, and
      mesenteric branch arteries were isolated for wire myograph analysis and confocal
      based measurement of calcitonin gene-related peptide (CGRP) positive nerve
      density. RESULTS: No differences in BP were detected. Serum glucose,
      triglycerides, and cholesterol were significantly elevated in ZDF. Sensory nerve
      dependent vasodilation was assessed by measuring relaxation of phenylephrine
      preconstricted arterial segments to cumulative addition of divalent calcium ion
      (Ca2+) or capsaicin. Neither Ca(2+)-nor capsaicin-induced relaxation were
      different in ZDF versus control (maximal ZDF response to Ca2+ = 64% +/- 2% v 59%
      +/- 4%; ED50 for Ca2+ = 3.7 +/- 0.5 mmol/L v 3.2 +/- 0.5 mmol/L; n = 5, P = not
      significant [NS]; maximal ZDF response to capsaicin = 68% +/- 9% v 74% +/- 4%;
      ZDF ED50 = 3.8 +/- 0.5 nmol/L v 9.8 +/- 7 nmol/L; n = 5, P = NS). In contrast,
      the maximal relaxation response to acetylcholine was impaired in ZDF (maximal ZDF
      response = 83% +/- 5% v 94% +/- 2%, n = 4, P = .039; ED50 for acetylcholine = 8.1
      +/- 2.9 nmol/L for ZDF v 33.5 +/- 18.2; n = 4 per group, P = .086). The CGRP
      positive nerve density was not different between groups. CONCLUSIONS: Blood
      pressure, perivascular sensory nerve CGRP content, and dilator function is normal
      in the ZDF model of type II diabetes, whereas endothelium-dependent relaxation is
      impaired.

PMID- 11991216
TI  - Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and
      fibrinogen in hypertensive type 2 diabetic patients.
AB  - BACKGROUND: This study compared the effects of losartan and perindopril on plasma
      plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in hypertensive type 2
      diabetic patients. METHODS: We studied 85 nonsmoking outpatients, aged 46 to 64
      years, with mild to moderate essential hypertension (diastolic blood pressure
      [BP] > 90 and < 110 mm Hg) and well controlled type 2 diabetes mellitus. After a
      4-week washout placebo period, patients were randomized to received perindopril 4
      mg once daily (n = 42) or losartan 50 mg once daily (n = 43) for 12 weeks
      according to a double-blind, parallel-group design. At the end of the placebo and
      active treatment periods, BP was measured and plasma PAI-1 and fibrinogen were
      evaluated. RESULTS: Both perindopril and losartan reduced systolic and diastolic
      BP values (-16/15 mm Hg and -15/14, respectively; P < .001 v placebo), with no
      difference between the two treatments. Plasma PAI-1 was reduced by perindopril (
      10 ng/dL, P = .028 v placebo) but not by losartan (+4 ng/dL, NS), the difference
      between the two treatments being statistically significant (P < .01). Plasma
      fibrinogen showed no significant change with both drugs, although a decreasing
      trend was noted with perindopril. CONCLUSIONS: These findings indicate that
      perindopril but not losartan decreases PAI-1 in hypertensive type 2 diabetic
      patients, which suggests that the PAI-1 lowering effect is unrelated with AT,
      receptor blockade and could rather be due to the fact that the endothelial
      receptors that mediate PAI-1 expression in response to angiotensin II are not
      type 1 receptor subtypes. Different effects of the two drugs on the bradykinin
      system might also be implicated.

PMID- 11991217
TI  - Reduction in arterial stiffness with angiotensin II antagonist is comparable with
      and additive to ACE inhibition.
AB  - We measured the effects of angiotensin II blockade on arterial stiffness,
      augmentation index (AI%), pulse wave velocity (PWV), and blood pressure (BP) in
      12 hypertensive patients (mean 49 +/- 11 years) in a 4-week, randomized, cross
      over study comparing valsartan 160 mg/day with captopril 100 mg/day, with a 2
      week washout period. Subsequently both therapies were combined. Reductions in PWV
      and AI% remained significant when corrected for BP. Combined therapy reduced PWV
      and AI% (P < .05) more than monotherapy, even when corrected for BP. The study
      shows that angiotensin receptor antagonists reduce arterial stiffness in
      hypertension comparable with and possibly additive to angiotensin converting
      enzyme inhibition.

PMID- 11991218
TI  - Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both
      normotensive and hypertensive individuals.
AB  - BACKGROUND: A deficiency of tetrahydrobiopterin (BH4), an essential cofactor for
      nitric oxide (NO) synthase, decreases NO synthesis and increases superoxide
      production. Supplementation of BH4 has been postulated to improve endothelial
      function in atherosclerotic patients. The purpose of this study was to determine
      whether BH4 restores endothelium-dependent vasodilation in patients with
      essential hypertension. METHODS: We evaluated the effects of BH4 on forearm
      vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator,
      and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, both in
      patients with essential hypertension and in age- and sex-matched normal control
      subjects. Forearm blood flow (FBF) was measured using strain gauge
      plethysmography. RESULTS: The response of FBF to ACh was less in hypertensive
      patients (n = 8) than in normal control subjects (n = 8). There was no
      significant difference in FBF response to ISDN in the two groups. During
      coinfusion of BH4 (500 mg/min), the FBF response to ACh in hypertensive patients
      increased significantly (14.8 +/- 4.6 to 25.6 +/- 7.3 mL/min/100 mL tissue, P <
      .05) to the level of normal control subjects. In the control subjects, also, BH4
      augmented the FBF response to ACh (27.8 +/- 8.7 to 36.1 +/- 9.6 mL/min/100 mL
      tissue, P < .05). The increase in FBF after ISDN was not altered by BH4 in either
      group (each group, n = 6). CONCLUSION: Supplementation of BH4 augments
      endothelium-dependent vasodilation in both normotensive and hypertensive
      individuals.

PMID- 11991219
TI  - The role of spironolactone in the treatment of patients with refractory
      hypertension.
AB  - BACKGROUND: Hypertension is resistant to pharmacologic therapy in 5% to 10% of
      patients. The current study tested whether addition of spironolactone to the
      treatment of patients with refractory hypertension would lead to adequate blood
      pressure (BP) control. METHODS: Among 520 patients who were referred for
      treatment of hypertension to one medical clinic from 1997 to 1999, a total of 25
      patients who met the inclusion criteria of refractory hypertension were
      prospectively included in this study. The inclusion criteria were as follows: 1)
      hypertension of > or = 6 months without any apparent cause; 2) clinical BP
      measurement and mean 24-h ambulatory BP monitoring > 140/90 mm Hg despite
      treatment with at least two antihypertensive drugs; 3) no prior therapy with
      spironolactone; and 4) no renal insufficiency. Spironolactone was added to the
      previous regimen at a dosage of 1 mg/kg/day while any angiotensin converting
      enzyme inhibitor was suppressed. Serum potassium and creatinine levels were
      checked before the introduction of spironolactone and 1 month later. RESULTS:
      After 1 month of therapy with spironolactone, 23 patients had a clinical BP <
      140/90 mm Hg. Ambulatory BP monitoring when compared before and 1 month after
      initiation of spironolactone decreased significantly (systolic BP from 152 +/- 2
      mm Hg to 128 +/- 2 mm Hg, P < .001; and diastolic BP from 86 +/- 2 mm Hg to 76 +/
      2 mm Hg, P < .013). By 3 months after the introduction of spironolactone, the
      mean number of antihypertensive drugs required per patient was significantly
      reduced (from 3.2 +/- 0.2 to 2.1 +/- 0.2, P < .001). No patient required
      discontinuation of spironolactone due to adverse renal effects. CONCLUSION:
      Spironolactone is a safe, effective therapy for patients with refractory
      hypertension.

PMID- 11991220
TI  - Echocardiographic comparison of left ventricular structure and function in
      hypertensive patients with primary aldosteronism and essential hypertension.
AB  - BACKGROUND: In experimental renovascular hypertension, aldosterone has been
      implicated in myocardial remodeling and fibrosis, but it is uncertain whether
      excess aldosterone effects left ventricular structure and function in
      hypertensive patients. METHODS: Hypertensive patients from the Cardiovascular
      Center of the New York Presbyterian Hospital-Weill Cornell Medical Center in New
      York and the Russian Cardiovascular Research Institute, Moscow, Russia, were
      studied. The sample included 35 patients with primary aldosteronism and 35
      controls with essential hypertension matched for age, gender, and blood pressure
      (BP). Left ventricular (LV) mass, endocardial and midwall fractional shortening,
      and circumferential end-systolic stress were calculated. The observed/predicted
      midwall shortening ratio was used as an index of LV performance corrected for
      afterload. RESULTS: Primary aldosteronism and essential hypertension patients had
      comparable LV dimensions, wall thickness, mass, mass/body surface area, and
      mass/height. Endocardial and midwall fractional shortening, and afterload
      corrected midwall shortening were similar in primary aldosteronism and essential
      hypertension groups from both clinics. Moreover, logistic regression analysis
      using BP, body mass index, height, gender, and center as covariates failed to
      identify statistical differences in LV geometry or systolic function between
      primary aldosteronism and essential hypertension patients. CONCLUSIONS: Patients
      with primary aldosteronism, a state characterized by chronic aldosterone excess,
      had similar LV geometry and systolic function compared to essential hypertension
      patients matched for age, gender, and BP. This argues against important
      independent associations between aldosterone and these aspects of LV response to
      human hypertension.

PMID- 11991221
TI  - Stress-induced renal alterations in normotensives offspring of hypertensives and
      in hypertensives.
AB  - BACKGROUND: Scarce information is available on stress-induced renal behavior in
      humans, especially in normotensives offspring of hypertensives (HP) and in
      hypertensives (HT). METHODS: Ten HP and 10 HT were compared to 10 normotensives
      with normotensive parents (NP). Systolic blood pressure (SBP) and renal
      functional parameters were determined during rest and stress periods. RESULTS:
      The stress SBP reactivity was significantly (P < .05) higher in HP than in NP and
      HT. At rest, HP were characterized by a significantly (P < .05) higher glomerular
      filtration rate. Stress significantly reduced glomerular filtration rate (-14 +/-
      4 mL/min/1.73 m2, P < .05) only in HT. Renal plasma flow significantly (P < .05)
      decreased during stress in NP (-35 +/- 16 mL/min/1.73 m2) and in HT (-49 +/- 25
      mL/min/1.73 m2), whereas it did not change in HP. The resulting filtration
      fraction increased significantly during stress only in NP (1.5% +/- 0.6%, P <
      .05). Despite the increase in BP, stress induced a similar decrease in sodium
      excretion rate in NP (-52 +/- 26 micromol/min) and in HT (-56 +/- 24
      micromol/min). The stress-induced sodium reabsorption occurred only in the
      proximal part of the tubules (lithium clearance). In HP, stress did not alter
      either sodium excretion rate or plasma renin activity. CONCLUSIONS: The stress
      induced renal modifications are characterized by an efferent vasoconstriction and
      a paradoxical increase in sodium reabsorption that occurred in the proximal part
      of the tubules in NP. In HP, genetically at risk of hypertension, basal renal
      alterations may explain a different stress-induced renal behavior. In HT, stress
      induced increase in sodium reabsorption may be involved in the sustained BP
      level.

PMID- 11991222
TI  - Short- and long-term effects of ferulic acid on blood pressure in spontaneously
      hypertensive rats.
AB  - Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phenolic compound contained
      in rice bran and other plants. The effect of ferulic acid on blood pressure (BP)
      was investigated in spontaneously hypertensive rats (SHR). After oral
      administration of ferulic acid (1 to 100 mg/kg) to SHR, systolic blood pressure
      (SBP) significantly decreased in a dose-dependent manner. When oral ferulic acid
      (50 mg/kg) was administered to SHR, BP was lowest at 1 h and returned to basal
      levels at 6 h. There was a significant correlation between SHR plasma ferulic
      acid and changes in the SBP of the tail artery, suggesting that absorbed ferulic
      acid reduces BP. When 7-week-old SHR were given 10 and 50 mg/kg/d of ferulic acid
      for 6 weeks, increases in BP were significantly attenuated compared to SHR on the
      control diet. Intravenous injection of ferulic acid dose dependently reduced
      carotid arterial pressure in anesthetized SHR. Furthermore, the depressor effect
      of intravenous ferulic acid (1 mg/kg) was significantly attenuated by
      pretreatment of SHR with the nitric oxide (NO) synthase inhibitor NG-nitro-L
      arginine methyl ester (L-NAME; 3 mg/kg, administered intravenously). These data
      suggest that the hypotensive effect of ferulic acid in SHR is associated with NO
      mediated vasodilation.

PMID- 11991223
TI  - Effects of age, race, gender, blood pressure, and estrogen on arterial
      compliance.
AB  - BACKGROUND: Although a variety of factors have been shown to influence vascular
      compliance in humans, few studies have been large enough to adequately assess the
      effects of age, race, gender, blood pressure (BP), and estrogen therapy. METHODS:
      As part of a long-term follow-up study, 272 subjects, 50% women, 26% African
      American, 71% currently hypertensive, ranging in age from 33 to 80 years were
      studied with noninvasive measures of vascular compliance by pulse wave analysis.
      RESULTS: A significant age-related decrease in large and small vessel compliance
      and increase in vascular resistance and impedance was seen in all hypertensive
      subjects and in normotensive women. The slope of the relationship was
      significantly steeper for women than for men. No effect of estrogen or race could
      be observed. In hypertensive subjects, pulse pressure exerted an effect similar
      to that of age. CONCLUSIONS: Studies of vascular compliance must consider a
      variety of demographic and physiologic factors including age, gender, and BP.
      Race and estrogen administration do not appear to contribute to the variables
      independent of the factors identified.

PMID- 11991224
TI  - Nocturnal blood pressure dipping and beta-adrenergic receptor sensitivity.
AB  - BACKGROUND: Blunted nocturnal blood pressure (BP) dipping has been observed in
      patients with various cardiovascular pathophysiology. However, the mechanisms
      underlying relationships between blunted dipping and pathophysiologic end points
      remain unclear. This study examined relationships between beta-adrenergic
      receptor sensitivity and nocturnal BP dipping. METHODS: Ambulatory BP monitoring
      took place in each patient's home. On a separate occasion, beta-adrenergic
      receptor sensitivity was determined by response to isoproterenol infusion.
      RESULTS: Participants with less sensitive beta-adrenergic receptors had less
      nocturnal BP dipping across BP measures (all P < .001). CONCLUSIONS: These
      findings suggest that beta-adrenergic receptor sensitivity may contribute to
      relationships between blunted nocturnal BP dipping and various cardiovascular end
      points.

PMID- 11991225
TI  - ACE inhibition and cardiovascular mortality and morbidity in essential
      hypertension: the end of the search or a need for further investigations?
AB  - Scientific evidence currently available supports the concept that renin
      angiotensin blockade with angiotensin converting enzyme inhibitors as a first
      line treatment exhibits in arterial hypertension beneficial effects in the
      prevention of mortality and morbidity comparable to those achieved with diuretics
      and beta-blockers. In addition, the renin-angiotensin blockade has also proved to
      be beneficial in the secondary prevention of several complications of
      hypertensive disease such as after myocardial infarction and congestive heart
      failure, as well as in the prevention of the incidence of type 2 diabetes, and
      the progression of diabetic and nondiabetic nephropathy. In this later regard,
      recent evidence with angiotensin II receptor antagonists in reducing the
      progression of nephropathy in type 2 diabetes strongly confirms that antagonism
      of the renin-angiotensin system is an effective approach to cardiovascular and
      renal disease. Finally, the renin-angiotensin blockade in high-risk patients may
      reduce cardiovascular mortality independently of the effect on blood pressure
      (BP). The effect of other antihypertensive drugs on cardiovascular risk in
      patients with high-normal BP should be investigated to establish whether they
      exhibit a comparable effect or whether there is a class-related benefit of drugs
      blocking the renin-angiotensin system. Such a strategy could also be encouraged
      to design future interventional studies with the newer classes of compounds
      (angiotensin II AT1-receptor antagonists, vasopeptidase inhibitors, endothelin
      antagonists), which would have the additional potential advantage of providing
      information more easily transferable to large-scale clinical practice.

PMID- 11991226
TI  - American Society of Hypertension regional chapters: leveraging the impact of the
      clinical hypertension specialist in the local community.
AB  - Hypertension control has remained at 24% to 27% for the past decade, despite
      revision of national treatment guidelines, expansion of therapeutic options, and
      evidence from clinical trials that higher control rates are attainable.
      Uncontrolled hypertension contributes to the enormous health and economic burden
      from cardiovascular and renal disease. The risk for hypertension-related
      complications is increasing in the United States as comorbidities such as
      diabetes mellitus and congestive heart failure rise in a population that is
      becoming progressively older, more obese, and more ethnically diverse. Given
      regional variations in demographic characteristics and disease burdens,
      implementing evidence-based guidelines will be more effective if tailored
      appropriately to the local community. The Clinical Hypertension Specialist
      program is a positive response to an impending health care crisis. The impact of
      the Hypertension Specialist on blood pressure control can be leveraged by
      extending the academic mission of education, patient care, and health services
      research to the local community. The American Society of Hypertension regional
      chapter can serve as a forum for Clinical Hypertension Specialists from academic
      medicine and the community to define mutual goals, develop an action plan which
      is responsive to community needs, and monitor progress. With support from the
      chapter, Clinical Hypertension Specialists in the community can have an impact on
      the practice of medicine locally by contributing to the education of primary care
      providers, receiving referrals of patients with complicated hypertension,
      monitoring progress in meeting evidence-based goals, providing feedback to peers,
      and participating in multicenter trials.

PMID- 11991227
TI  - Modulation of noradrenaline-induced vasoconstriction in isolated perfused
      mesenteric arterial beds from obese Zucker rats in the presence and absence of
      insulin.
AB  - The genetically obese Zucker rat (fa/fa) is an insulin-resistant animal model
      with early-onset severe hyperinsulinemia that eventually develops mild
      hypertension. Thus, it represents a model in which the effect of hyperinsulinemia
      - insulin resistance associated with hypertension on vascular reactivity can be
      examined. The purpose of this study was to investigate the contribution of
      endogenous nitric oxide (NO) and prostaglandins to reactivity to noradrenaline
      (NA) in the presence and absence of insulin in mesenteric arterial beds (MAB)
      from 25-week-old obese Zucker rats and their lean, gender-matched littermates. In
      the absence of insulin, bolus injection of NA (0.9-90 nmol) produced a dose
      dependent increase in perfusion pressure in MAB from both lean and obese rats.
      Although there was no significant difference in NA pD2 (-log ED50) values, the
      maximum response of MAB from obese rats to NA was slightly but significantly
      reduced compared with that of MAB from lean rats. The nitric oxide synthase
      inhibitor NG-monomethyl-L-arginine (L-NMMA, 300 microM) enhanced and indomethacin
      (20 microM) inhibited pressor responses to NA in MAB from both obese and lean
      rats. Perfusion with insulin (200 mU/L, a level similar to that in obese rats in
      vivo) potentiated only the responses of the obese MAB to the two lowest doses of
      NA tested (0.9 and 3 nmol). In the presence of L-NMMA, insulin further
      potentiated the NA response in MAB from obese rats. Indomethacin, the
      prostaglandin H2/thromboxane A2 receptor antagonist SQ 29548 (0.3 microM), and
      the nonselective endothelin-1 (ET-1) receptor antagonist bosentan (3 microM) all
      abolished insulin potentiation of the NA response in obese MAB. These data
      suggest that concurrent release of NO and vasoconstrictor cyclooxygenase
      product(s) in MAB from both obese and lean Zucker rats normally regulates NA
      induced vasoconstrictor responses. Furthermore, insulin increases the release of
      contracting cyclooxygenase product(s) and enhances reactivity to low doses of NA
      in MAB from obese rats. The effects of insulin may be partially mediated by ET-1
      via ET receptors and are buffered to some extent by concomitant NO release. This
      altered action of insulin may play a role in hypertension in this
      hyperinsulinemic - insulin-resistant model.

PMID- 11991228
TI  - Plasma constituents and mortality in rat pups given chronic insulin via
      injection, pellet, or osmotic minipump.
AB  - Two studies compared the glucose responses of 9-day-old rats given subcutaneous
      insulin, either continuously or via daily injection, for 10 days. In Experiment
      1, implanted pellets released a total of 0, 1.9, or 5.7 U insulin/kg the first 24
      h. Injected doses were larger, 0 or 8 U/kg. Injections caused no deaths, but
      insulin-releasing pellets caused high mortality within 24 h. Pups surviving the
      pellets were normoglycemic by treatment day 8. In Experiment 2, pups received
      0.184 U of insulin daily, approximately 8 U/kg at 9 days, via either injection or
      osmotic minipump. All pups survived. Injected pups were hypoglycemic 2 h
      postinjection through treatment day 10, whereas pups with insulin minipumps were
      normoglycemic by day 5. Insulin injections, but not minipumps, lowered plasma
      triglycerides on day 10. To examine age differences in response to insulin,
      additional pups and adults received daily injections of 0 or 8 U/kg for 10 days.
      All survived. Insulin lowered plasma glucose more in pups than in adults and
      reduced triglycerides in pups but not in adults. The rapid development of
      normoglycemia in pups with insulin minipumps, compared with pups injected daily
      with the same dose, suggests that continuous early insulin may produce insulin
      resistance.

PMID- 11991229
TI  - Sleep deprivation reduces total plasma homocysteine levels in rats.
AB  - Hyperhomocysteinemia has been associated with pathological and stressful
      conditions and is a risk factor for cardiovascular disease. Since sleep
      deprivation is a stressful condition that is associated with disruption of
      various physiological processes, we investigated whether it would also be
      associated with increases in plasma homocysteine levels. Further, since
      hyperhomocysteinemia may promote oxidative stress, and we had previously found
      evidence of oxidative stress in brain following sleep deprivation, we also
      searched for evidence of systemic oxidative stress by measuring glutathione and
      thiobarbituric acid reactive substance levels. Rats were sleep deprived for 96 h
      using the platform technique. A group was killed after sleep deprivation and
      another two groups were allowed to undergo sleep recovery for 24 or 48 h.
      Contrary to expectation, plasma homocysteine was reduced in sleep-deprived rats
      as compared with the control group and did not revert to normal levels after 24
      or 48 h of sleep recovery. A trend was observed towards decreased glutathione and
      increased thiobarbituric acid reactive substance levels in sleep-deprived rats.
      It is possible that the observed decreases in homocysteine levels may represent a
      self-correcting response to depleted glutathione in sleep-deprived animals, which
      would contribute to the attenuation of the deleterious effects of sleep
      deprivation.

PMID- 11991230
TI  - Structure-activity relationship on (+/-)-nantenine derivatives in
      antiserotonergic activities in rat aorta.
AB  - A series of nine (+/-)-nantenine derivatives were synthesized and assayed for
      their pharmacological activities by using tension in aorta and binding
      experiments in rat brain membrane. Replacing a methyl group with a hydrogen ((+/
      )-nornantenine) and an ethyl group at a nitrogen atom ((+/-)-ethylnornantenine)
      or introducing a hydroxyl group at the alpha/beta position of C-4 or displacement
      of a methoxy moiety at the C-1 position with a hydroxyl ((+/-)-domesticine) of
      (+/-)-nantenine decreased the affinity. Moreover, changing a methyl group of (+/
      )-domesticine to hydrogen at a nitrogen atom ((+/-)-nordomesticine) caused loss
      of the activities. These results suggest that a methyl group at a nitrogen atom
      and a methoxy moiety at C-1 play important roles in the development of the
      antiserotonergic activity. Molecular modeling analysis of the interaction between
      the 5-HT2A receptor and (+/-)-nantenine suggested that electron lone pairs of N-6
      and of the oxygen atom of the methoxy group at C-1 are important in forming a
      hydrogen bond to Asp155 and Asn343 of the 5-HT2A receptor, respectively.

PMID- 11991231
TI  - A fluorescent compound for glucose uptake measurements in isolated rat
      cardiomyocytes.
AB  - A focus of current diabetes research is the development of insulinomimetic
      compounds for oral treatment of diabetes and its associated cardiac
      complications. Screening compounds for their potential insulinomimetic effects
      usually involves the use of radioactive isotopes. The focus of this study was to
      investigate a nonradioactive fluorescent compound for its use in screening
      insulinomimetic compounds. The indicator 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino)-2-deoxyglucose (2-NBDG) has been used by some workers to measure
      glucose uptake in Escherichia coli and Candida albicans. We propose that 2-NBDG
      will also be a suitable indicator for mammalian cell lines, in particular rat
      cardiomyocytes. We found that the indicator could give a reliable reproducible
      standard curve following appropriate dilution and is taken up by isolated
      cardiomyocytes. The insulinomimetic compounds vanadyl sulfate and sodium
      molybdate showed rates of glucose uptake similar to that of insulin. Furthermore,
      the rate of uptake measured for insulin using this technique (0.04 +/- 0.003 nmol
      x min(-1) x 10(6) cells(-1) is comparable with previous literature using 2
      deoxyglucose uptake measurements on isolated myocytes (0.040 nmol x min(-1) x
      10(6) cells(-1), demonstrating the validity of this fluorescent compound for
      glucose uptake studies.

PMID- 11991232
TI  - Enhanced protection by melatonin and meloxicam combination in a middle cerebral
      artery occlusion model of acute ischemic stroke in rat.
AB  - Mixed efficacy of neuroprotective drugs in clinical trials has led to the
      emergence of the approach of combination therapy in stroke. The present study was
      carried out to investigate the effect of the combination of melatonin (potent
      antioxidant) and meloxicam (preferential inhibitor of cyclooxygenase-2 enzyme)
      against a middle cerebral artery occlusion model of stroke in rats. Male Wistar
      rats in the weight range of 250-300 g were used. Rats were anesthetized using
      chloral hydrate (400 mg/kg i.p) and subjected to 2 h of transient middle cerebral
      artery occlusion. Melatonin was administered at a dose of 20 mg/kg i.p. four
      times: at the time of middle cerebral artery occlusion, 1.5 h after middle
      cerebral artery occlusion, at the time of reperfusion, and 1 h after reperfusion.
      Meloxicam (2.5 mg/kg) was administered 4 h after middle cerebral artery
      occlusion. Motor performance tests (grip test, foot fault test, rotarod
      performance test, spontaneous locomotor activity), markers of oxidative stress,
      and triphenyltetrazolium chloride staining were carried out 24 h after middle
      cerebral artery occlusion. A vehicle-treated group was run in parallel. It was
      observed that melatonin treatment improved the motor performance and
      significantly attenuated the levels of malondialdehyde (MDA) as compared with the
      middle cerebral artery occluded group. Meloxicam treatment at the dose used
      neither showed significant improvement on the motor performance nor decreased the
      levels of MDA significantly as compared with the middle cerebral artery occluded
      group. However, when the combination of the two drugs was used, better protection
      was observed as was evident by the significant decrease in the percent foot fault
      errors, the increase in the time spent on the rotarod, and the increase in the
      six-point neurological score and grip test score. There was also a significant
      decrease in the levels of MDA in the combination group. The results of the
      present study demonstrate that enhanced protection is observed with the use of a
      combination of melatonin plus meloxicam in the middle cerebral artery occlusion
      model of acute ischemic stroke in rats.

PMID- 11991233
TI  - Altered coronary and cardiac adrenergic response in the failing hamster heart:
      role of cyclooxygenase derivatives.
AB  - Although the influence of the adrenergic system has been studied in the presence
      of heart failure, controversies still exist. Since cyclooxygenase derivatives
      appear to modulate coronary and cardiac adaptation in the failing heart, we
      hypothesized that cyclooxygenase derivatives may participate in the altered
      adrenergic responses in this situation. Isolated hearts from cardiomyopathic (UM
      X7.1 subline) and normal hamsters, aged > 240 days, were utilized. Coronary and
      cardiac response to alpha1-, beta1-, and beta2-adrenergic stimulations was
      observed before and after pretreatment with indomethacin, a cyclooxygenase
      inhibitor. Reduction of coronary flow elicited by alpha1-adrenergic stimulation
      was unchanged in the presence of heart failure, while beta1- and beta2-induced
      vasodilatations were reduced. Inotropic response to alpha1 and beta1 stimulations
      were also reduced in failing hearts, while beta2-adrenergic action was unchanged.
      Pretreatment with indomethacin exacerbated coronary flow reduction observed with
      alpha1 stimulation in failing hearts only. Beta2-induced coronary vasodilatation
      and inotropic response to alpha1 and beta2 stimulations were impaired similarly
      in the presence of indomethacin in normal and failing hearts. The results suggest
      a complex interaction between adrenergic and cyclooxygenase activation.

PMID- 11991234
TI  - MK801 impairs thermoregulation in the heat.
AB  - The effects of MK801 (dizocilpine), a glutamate NMDA receptor antagonist, on
      thermoregulation in the heat were studied in awake rats exposed to 40 degrees C
      ambient temperature until their body core temperature reached 43 degrees C. Under
      these conditions, MK801-treated rats exhibited enhanced locomotor activity and a
      steady rise in body core temperature, which reduced the heat exposure duration
      required to reach 43 degrees C. Since MK801-treated rats also showed increased
      striatal dopaminergic metabolism at thermoneutrality, the role of dopamine in the
      MK801-induced impairment of thermoregulation in the heat was determined using co
      treatment with SCH23390, a dopamine D1 receptor antagonist. SCH23390 normalized
      the locomotor activity in the heat without any effect on the heat exposure
      duration. These results suggest that the MK801-induced impairment of
      thermoregulation in the heat is related to neither a dopamine metabolism
      alteration nor a locomotor activity enhancement.

PMID- 11991235
TI  - Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and
      rewarmed rats.
AB  - The effects of hypothermia and rewarming on endothelial integrity were examined
      in intestines, kidney, heart, gastrocnemius muscle, liver, spleen, and brain by
      measuring albumin-bound Evans blue loss from the vasculature. Ten groups of
      twelve rats, normothermic with no pentobarbital, normothermic sampled at 2, 3, or
      4 h after pentobarbital, hypothermic to 20, 25, or 30 degrees C, and rewarmed
      from 20, 25, or 30 degrees C, were cooled in copper coils through which water
      circulated. Hypothermic rats were cooled to the desired core temperature and
      maintained there for 1 h; rewarmed rats were cooled to the same core
      temperatures, maintained there for 1 h, and then rewarmed. Following Evans blue
      administration, animals were euthanized with methoxyflurane, tissues removed, and
      Evans blue extracted. Because hypothermia and rewarming significantly decrease
      blood flow, organ-specific flow rates for hypothermic and rewarmed tissues were
      used to predict extravasation. Hypothermia decreased extravasation in tissues
      with continuous endothelium (brain, muscle) and increased it in tissues with
      discontinuous endothelium (liver, lung, spleen). All tissues exhibited
      significant (p < 0.05) differences from normothermic controls. These differences
      are attributed to a combination of anesthesia, flow, and (or) change in
      endothelial permeability, suggesting that appropriate choice of organ and
      temperature would facilitate testing pharmacological means of promoting return to
      normal perfusion.

PMID- 11991236
TI  - Disseminated intravascular coagulation: a review of etiology, pathophysiology,
      diagnosis, and management: guidelines for care.
AB  - The pathophysiologic mechanisms, clinical, and laboratory manifestations of DIC
      are complex in part due to interrelationships within the hemostasis system. Only
      by clearly understanding these extraordinarily complex pathophysiologic
      interrelationships can the clinician and laboratory scientist appreciate the
      divergent and wide spectrum of often confusing clinical and laboratory findings
      in patients with DIC. Many therapeutic decisions to be made are controversial and
      lack validation. Nevertheless, newer antithrombotic agents, and agents that can
      block, blunt, or modify cytokine activity and the activity of vasoactive
      substances appear to be of value. The complexity and variable degree of clinical
      expression suggests that therapy should be individualized depending on the nature
      of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and
      hemodynamics and other appropriate clinical parameters. At present, treatment of
      the triggering event, low-dose heparin or antithrombin concentrate and wise
      choice of components when indicated appear to be the most effective modes of
      therapy.

PMID- 11991237
TI  - Phosphatidylserine expression on the platelet membrane of patients with
      myeloproliferative disorders and its effect on platelet-dependent thrombin
      formation.
AB  - Recently, the asymmetric distribution of phospholipids in eukaryotic cell
      membranes has been appreciated and been found to be dependent on the activity of
      a number of enzymes. The expression of phosphatidylserine (PS), a negatively
      charged phospholipid, on the platelets of patients with polycythemia vera (P
      vera) and essential thrombocythemia (ET) was compared to that in normal
      individuals. The effect of platelet aggregation on PS expression was determined.
      Exposure of PS on platelets obtained from patients with P vera and ET and from
      age- and sex-matched healthy volunteers was measured by fluorescein-labeled
      Annexin V binding to platelets and by the platelets' thrombin-generating capacity
      determined by the prothrombinase assay. PLatelet prothrombinase activity (mean +/
      standard deviation [SD]), as measured by thrombin generation, was 2.32+/-2.2
      micro/mL in the P vera group and 1.55+/-1.0 micro/mL in the control group
      (p=0.3). PS expression as measured by Annexin V binding (mean +/- SD) was 2.6+/
      2.4 % in the P vera group versus 1.55+/-1.2% among controls (p=0.03). In the ET
      group, prothrombinase activity (mean +/- SD) was 1.0+/-0.6 micro/mL and 2.1+/-0.9
      micro/mL in the control group (p=0.006). Annexin V binding (mean +/- SD) was
      4.8+/-4.2% in the ET group and 2.77+/-2.1% among control subjects (p=0.09). When
      the prothrombinase assay was performed after addition of adenosine diphosphate
      (ADP) to the platelets, there was a significant increase in thrombin generation
      in the myeloproliferative disorder (MPD) group (3.1+/-2.0 micro/mL) compared to
      the thrombin generated by unstimulated myeloproliferative disorder platelets
      (2.07+/-1.69 micro/mL) (p=0.0006). An increase in thrombin generation was seen in
      the ADP-stimulated platelet samples in all ten paired samples studied. Likewise,
      the addition of ADP to control platelets increased thrombin generation from 2.0+/
      1.0 micro/mL in unstimulated platelets to 4.3+/-1.6 micro/mL in ADP-treated
      platelets (p=0.0006). Thrombin generation increased in all of the ADP-stimulated
      platelet samples compared to the untreated platelets. There was however, no
      difference in the increased thrombin generation when ADP-stimulated platelets
      from MPD patient and control subjects were compared (p=0.3). Results indicate
      that some patients with MPDs may show increased PS expression on platelet
      surface. When analyzed overall, there was a tendency toward greater PS expression
      in the P vera and ET patient groups; however, the increase did not reach
      statistical significance. This increase was noted in both the prothrombinase
      assay the Annexin V binding assay. We have also shown that stimulation of
      platelets by addition of the agonist ADP results in enhanced PS expression, which
      appears increase the thrombogenic potential of the platelets as demonstrated by
      the enhanced thrombin generation demonstrated by these platelets in the
      prothrombinase assay. There was no difference in the degree of PS expression in
      response to ADP stimulation between MPD and control platelets. Results show that
      PS expression and platelet-dependent thrombin generation is variable in patients
      with MPDs. This expression is increased after platelet aggregation occurs. The
      role of PS expression in the thromboembolic complications of MPD patients should
      be studied further.

PMID- 11991238
TI  - Diminished global fibrinolytic capacity in patients with mitral valve prolapse is
      associated with transient ischemic attacks.
AB  - Although mitral valve prolapse (MVP) has shown to be associated with
      thromboembolic complications, the cause of thromboembolic events in those
      patients is still unknown. The purpose of this study was to evaluate the
      fibrinolytic activity in MVP patients. The study included 35 consecutive patients
      (25 women, mean age 25+/-11 years) with echocardiographically documented MVP and
      25 age- and sex-matched subjects as a control group. Four of MVP patients have a
      history of transient ischemic attack (TIA). Global fibrinolytic capacity (GFC), a
      new technique that examines the effectiveness of the entire fibrinolytic system,
      was measured. Global fibrinolytic capacity was found to be nonsignificantly
      increased in MVP patients (3.14+/-1.42 microg/mL) compared to those in control
      subjects (2.36+/-1.33 microg/mL) (p>0.05). However, in four of these MVP patients
      who had a history of transient ischemic attack, the GFC level was significantly
      lower than in patients who have no history of transient ischemic attack (1.67+/
      0.6 microg/mL vs 3.27+/-1.46 (microg/mL, p=0.003). Furthermore, the GFC levels of
      these four patients were less than those of controls (p=0.04). These results
      showed that global fibrinolytic activity was similar in MVP patients without a
      history of TIA and control subjects. However, MVP patients with a history of TIA
      had significantly decreased global fibrinolytic activity compared to controls and
      as well as MVP patients without a history of TIA.

PMID- 11991239
TI  - Interobserver agreement of complete compression ultrasound for clinically
      suspected deep vein thrombosis.
AB  - The interobserver variability of compression ultrasound of proximal and distal
      veins in clinically suspected deep vein thrombosis was assessed. One hundred one
      symptomatic legs of all patients referred for clinically suspected deep vein
      thrombosis on 21 consecutive workdays were examined by two investigators
      independently according to a standardized protocol of complete compression
      ultrasound (CCUS) with 28 predefined venous segments between groin and ankle.
      Incompressible vein segments were defined as thrombotic. Cohen's kappa
      coefficient was used to calculate interobserver variability regarding diagnosis
      of deep vein thrombosis. Kappa for entire lower extremity was 0.94 (95% CI, 0.87
      1). Kappa for proximal veins was 1; for calf veins 0.9 (95% CI, 0.79-1). For the
      posterior tibial veins and peroneal veins, kappa was 0.84 (95% CI, 0.66-1) and
      0.77 (95% CI, 0.59-0.94), respectively. The results show that almost complete
      interobserver agreement can be achieved in compression ultrasound of both
      proximal and distal deep veins conducted according to a standardized examination
      protocol in clinically suspected deep vein thrombosis.

PMID- 11991240
TI  - Reference ranges of the dilute tissue thromboplastin inhibition and dilute
      Russell's viper venom tests revisited.
AB  - Reference ranges for two well-recognized tests for the lupus anticoagulant were
      determined utilizing 98 healthy subjects. The purpose of the study was to compare
      the reference ranges for the dilute tissue thromboplastin inhibition test on this
      group of healthy subjects calculated by parametric and nonparametric statistical
      methods, and to compare these results with results obtained on subsets of 20 and
      40 randomly selected individuals from the group of 98. The same procedures were
      followed for the dilute Russell's viper venom test. Results were recorded in
      seconds of clotting times and in ratios (subject/mean of that set or subset).
      Statistical analysis revealed Gaussian distribution of the results in the large
      group as well as in each subset for both tests. The results showed more variation
      between sets of the dilute tissue thromboplastin inhibition test than of the
      dilute Russell's viper venom test. Nonparametrically calculated reference ranges
      were wider than those determined by a parametric method, especially if confidence
      intervals are provided for both reference ranges in the group of 94 controls or
      in a subset of 40 subjects. The nonparametric technique utilizes all data for the
      calculation of reference ranges of such sample sizes no matter how wide the
      results are spread. There was no significant difference between the reference
      ranges of subsets and the whole group (p > 0.05) calculated by both statistical
      techniques.

PMID- 11991241
TI  - Effects of extracorporeal circulation on thrombinantithrombin III and prothrombin
      fragment 1+2 levels.
AB  - Cardiopulmonary bypass may alter the factors responsible for normal hemostasis by
      exposing blood to nonendothelial surfaces, for example, extracorporeal circuits.
      To evaluate the probable effect of extracorporeal circulation on hemostasis, we
      measured thrombin-antithrombin III complex (TAT) and prothrombin fragment 1+2 (PF
      1.2) plasma levels, which are the biologic markers of in vivo coagulation, in 20
      patients who underwent coronary artery bypass grafting (CABG). Postoperative PF
      1.2 levels were higher in comparison to the preoperative concentrations of the
      parameter. Preoperative and postoperative TAT concentrations showed no
      statistically significant difference. The increment in the PF 1.2 levels in CABG
      patients might suggest ongoing subclinical hemostatic activation associated with
      CABG. Further investigations are needed to clarify the exact relationship between
      increased PF 1.2 levels and thrombotic complications observed in CABG patients.
      Hemostatis in CABG is still an enigma and remains to be eluciated.

PMID- 11991242
TI  - Effects of a low molecular weight heparin, bemiparin, and unfractionated heparin
      on hemostatic properties of endothelium.
AB  - Human endothelial cells synthesize and secrete a variety of molecules involved in
      fibrinolysis and coagulation. The effects of a low molecular weight heparin,
      Bemiparin, and unfractionated heparin (UFH) were compared on plasminogen
      activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA), tissue factor
      (TF), tissue factor pathway inhibitor (TFPI) release, and PAI-1 gene expression
      by human umbilical vein endothelial cells (HUVEC). Cell cultures were
      supplemented with Bemiparin or UFH at 1 or 10 U/mL. Culture media samples were
      obtained before the addition of the drugs and 2, 6, and 24 hours afterward to
      measure the antigen levels of TF, TFPI, t-PA, and PAI-1. RNA was obtained to
      study the endothelial expression of PAI-1 by reverse transcriptase-polymerase
      chain reaction (RT-PCR). Bemiparin at 1 U/mL resulted in a decreased messenger
      RNA (mRNA) PAI-1 expression, which remained unaltered when UFH had been added.
      PAI-1 levels increased after the cultures had been supplemented with either
      Bemiparin or UFH at both doses. UFH induced an increase in t-PA either at 1 or 10
      U/mL. Both doses of UFH, but not Bemiparin, induced an important increase in TF
      secretion. An increase in the TFPI levels was seen with UFH at 1 U/mL. The
      decrease in PAI-1 gene expression observed with a therapeutic dose of Bemiparin
      might confer this drug interesting profibrinolytic properties. The fact that
      Bemiparin, in contrast with UFH, does not induce an increase in TF could give
      this drug another positive feature.

PMID- 11991243
TI  - The role of the bone marrow examination in the diagnosis of immune
      thrombocytopenic purpura: case series and literature review.
AB  - The need for a bone marrow examination was assessed in patients with clinical and
      laboratory features consistent with ITP; the literature was reviewed. The records
      of all patients undergoing a bone marrow examination between January 1988 to
      January 1998 were retrospectively reviewed to determine which were motivated by
      the suspicion of ITP. Data were collected from hospital and outpatient medical
      and pathology records. Eighty-six patients with isolated thrombocytopenia (i.e.,
      normal white blood cell count, hemoglobin, peripheral smear and clotting studies)
      were studied. The bone marrow was consistent with ITP in 82 patients, (i.e.,
      normal or increased megakaryocytes and other hemopoietic lineages normal.) Four
      patients had decreased megakaryocytes, but all patients responded to
      corticosteroids. All 86 patients were followed up for a median of 22 months after
      bone marrow aspiration (range, 2-76 months.) During that time, none of the
      patients developed features to suggest an alternative diagnosis to ITP. The
      initial clinical and laboratory findings of 99 patients with acute leukemia were
      also reviewed; all had features atypical of ITP. These data suggest that routine
      performance of a bone marrow examination for the diagnosis of ITP is not
      necessary, provided that a thorough history and physical examination are
      performed and that the complete blood cell count, peripheral blood smear, and
      routine clotting studies show no abnormalities apart from thrombocytopenia. The
      findings of seven prior retrospective studies, two in adults and five in children
      are consistent with the previous findings. However, the value of marrow
      investigation in ITP remains unresolved and data from a large prospective study
      would be helpful.

PMID- 11991244
TI  - Effects of recombinant erythropoietin therapy on circulating endothelial markers
      in hemodialysis patients.
AB  - Effects of a 4-week course of recombinant human erythropoietin (rHuEpo) therapy
      on four circulating endothelium-derived cardiovascular risk markers were studied
      in 20 patients receiving maintenance hemodialysis in relation to surrogates of
      chronic inflammation, liver function, and arterial blood pressure. Soluble
      intercellular adhesion molecule-1 (sICAM-1), antigens of plasminogen activator
      inhibitor-1 (PAI-1:Ag) and von Willebrand factor (vWF:Ag), and soluble
      thrombomodulin (sTM) were determined by immunoenzymatic assays. C-reactive
      protein; alpha1 acid-glycoprotein; alpha1-antitrypsin; immunoglobulin M, A, and
      G; interleukin-6; lipoprotein(a); fibrinogen; total protein; albumin; total
      cholesterol; hepatitis B and C markers; liver enzymes; prothrombin time; and
      phosphorus were measured by routine methods. The rHuEpo treatment resulted in a
      25% increase in sICAM-1 (Wilcoxon's p = 0.001), a 50% increase in PAI-1:Ag (p =
      0.004), a 15% increase in sTM (p = 0.002), and did not change vWF:Ag levels. The
      increase in sICAM-1 concentration directly correlated with that of PAI-1:Ag
      (Spearman's rho = 0.483, p = 0.031). The rHuEpo-induced increases in hemoglobin,
      platelets, and pre-dialysis diastolic blood pressure levels did not correlate
      with the increments in the endothelial markers studied. In conclusion, short-term
      rHuEpo therapy activates vascular endothelium in patients receiving maintenance
      hemodialysis. This specific effect may influence cardiovascular risk.

PMID- 11991245
TI  - Buerger's disease and anticardiolipin antibodies: a worse prognosis?
AB  - The case of a 26-year-old male chronic smoker is reported, who had thrombotic
      incidences on three occasions in both upper and lower limbs over a 10-month
      period. Laboratory examinations, including hematologic studies and creatinine,
      cholesterol, and glucose levels, were normal. However, IgG and IgM
      anticardiolipin antibodies were detected. Duplex ultrasonography confirmed deep
      venous thrombosis in both lower limbs (two occurrences) and computer tomography
      depicted an inferior cava vein thrombosis. The patient fulfilled all of
      Shionoya's criteria for Buerger's disease, thus suggesting an association between
      anticardiolipin antibodies and this disease.

PMID- 11991246
TI  - Increased soluble thrombomodulin does not always indicate endothelial injury.

PMID- 11991247
TI  - Prothrombotic activity of oral contraceptives in patients with congenital
      thrombophilia.

PMID- 11991248
TI  - Role of tyrosinase in the genoprotective effect of the edible mushroom, Agaricus
      bisporus.
AB  - A heat-labile protein has been identified in fruit bodies of the edible mushroom,
      Agaricus bisporus, which protects Raji cells (a human lymphoma cell line) against
      H2O2-induced oxidative damage to cellular DNA. This protein has been purified
      following salt fractionation, combined with ion-exchange, hydrophobic interaction
      and adsorption chromatography. Based on catalytic and electrophoretic properties,
      and inhibition studies using tropolone, the protein was identified as tyrosinase.
      The genoprotective effect of A. bisporus tyrosinase, determined using the single
      cell gel electrophoresis met") assay, has been shown to be dependent upon the
      enzymic hydroxylation of tyrosine to L-DOPA and subsequent conversion of this
      metabolite to dopaquinone. The possible role of dopaquinone, and other L-DOPA
      oxidation products, in enhancing the cellular antioxidant defence mechanisms is
      discussed.

PMID- 11991249
TI  - Birth upregulates nitric oxide synthase activity in the porcine lung.
AB  - Developmental changes in the lung occur at birth, allowing for the transition
      from placental to air breathing. Here we have measured nitric oxide synthase
      (NOS) activity in the porcine lung pre and post partum. NOS activity, which was
      predominantly calcium dependent, was low in full term fetal tissue compared to
      that present in lungs from the newborn (5 minutes post partum), 1, 3, 6 and 14
      day old animals. No increase in activity was seen when fetal pigs were allowed to
      breathe for 5 minutes. Specific activity remained low in fetal tissue following
      partial purification. By contrast, levels of NOS III protein in tissue extracts
      and in pulmonary arterial endothelial cells, demonstrated by
      immunohistochemistry, were similar in tissue from the fetal and newborn animals.
      Thus NOS activity is significantly lower in fetal when compared to postnatal lung
      tissue despite comparable amounts of NOS III protein being expressed, and birth
      is followed by an abrupt increase in enzyme activity in animals born at term
      which correlates with an increase in protein expression.

PMID- 11991250
TI  - Effect of treatment with different doses of 17-beta-estradiol on the insulin
      receptor.
AB  - The mechanism for the development of insulin resistance in normal pregnancy is
      complex and is associated with serum levels of sex hormones. However, the
      influence of these hormones on the early steps of insulin action has not been
      extensively studied, although the potentially beneficial effect of estradiol on
      glucose homeostasis has been reported. In this paper, we attempted to determine
      the effect of 17-beta-estradiol on the insulin receptor of ovariectomized rats
      treated with different doses of hormones. Our results showed a tissue-dependent
      response to estradiol. We found that low doses of estradiol increased the amount
      of insulin receptors in liver and muscle on days 6 and 11 of treatment but not in
      adipose tissue, and after 16 days only the muscle responsed in this way. On the
      other hand, high doses of estradiol significantly decreased the amount of insulin
      receptors, at least in muscle and adipose tissue. We believe that the low
      concentrations of 17-beta-estradiol (similar to early pregnancy) could be
      responsible for the increase in insulin sensitivity by increasing the amount of
      insulin receptors in peripheral tissues. When the hormone levels were high
      (similar to late pregnancy) the amount of insulin receptors decreased in
      peripheral tissues, and insulin sensitivity is diminished just as in late
      pregnancy. The specific molecular mechanism for this action is as yet unknown.

PMID- 11991251
TI  - MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in
      the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat
      neuronal cells.
AB  - MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2
      pyrrolidinone L-tartrate) is a antipsychotic agent that binds to sigma-1
      receptor. MS-377 showed anti-dopaminergic and anti-serotonergic activities and
      antagonistic action against phencyclidine (PCP)-induced behaviors in an animal
      model. These anti-psychotic activities of MS-377 are attributable to association
      with sigma-1 receptor. However, the mechanism by which the sigma-1 receptor
      ligands exact those numerous effects remains to be elucidated. In the present
      study, we evaluated the effect of MS-377 on N-methyl-D-aspartate (NMDA) receptor
      ion-channel complex in primary cultured rat neuronal cells. First, we examined
      the effect of MS-377 on NMDA-induced Ca2+ influx with fura-2/ AM loaded cells. MS
      377 showed no effects on the basal Ca2+ concentration and NMDA-induced Ca2+
      influx by itself PCP and SKF-10047 reduced the NMDA-induced increase in
      intracellular Ca2+ concentration. Pre-incubation of 1 microM MS-377 was found to
      significantly block the reduction by PCP or SKF-10047 of the NMDA-induced Ca2+
      influx. Second, the effect of MS-377 on [3H]MK-801 intact cell binding was
      examined. PCP, haloperidol and (+)-pentazocine inhibited [3H]MK-801 binding,
      although MS-377 showed no effect by itself Pre-treatment of MS-377 markedly
      reversed the inhibition of [3H]MK-801 binding by PCP in a dose-dependent manner.
      These effects of MS-377 may depend on its affinity for the sigma-1 receptor,
      because MS-377 is a selective sigma-1 receptor ligand without any affinity for
      NMDA receptor ion-channel complex. These observations suggest that the MS-377
      indirectly modulated the NMDA receptor ion-channel complex, and the anti
      psychotic activities of MS-377, in part, are attributable to such on action via
      sigma-1 receptor.

PMID- 11991252
TI  - Differential regulation of activator protein 1 activity by glycyrrhizin.
AB  - Glycyrrhizin, a major component of Glycyrrhiza uralensis (licorice) root, is a
      saponin and exhibits a number of pharmacological effects, including anti
      inflammation, anti-ulcer, anti-allergy, and anticarcinogenesis. Activator protein
      I (AP-1), a nuclear transcription factor, consists of Jun/Fos heterodimers or
      Jun/Jun homodimers, and blocking of tumor promoter-induced AP-1 activity could
      inhibit induced cellular transformation. In order to elucidate the molecular
      mechanism of glycyrrhizin-induced anticarcinogenesis, effect of glycyrrhizin on
      the AP-1 activity in untreated and tumor promoter-12-O-tetradecanoylphorbol-13
      acetate (TPA)-treated conditions was analyzed in this study. Glycyrrhizin induced
      the AP-1/TATA reporter activity in a dose-dependent fashion, which was judged by
      chloramphenicol acetyltransferase assay and electrophoretic mobility-shift assay.
      Similar results were observed in HepG2 and Vero cells, suggested that
      glycyrrhizin effect was cell type-independent. In addition, the cis element
      responsible for glycyrrhizin activity was AP-1 responsive element. Further
      analysis indicated that glycyrrhizin exhibited a different regulation on the AP-1
      activity in untreated and TPA-treated cells. Glycyrrhizin induced the AP-1
      activity in untreated cells, while it inhibited the TPA-induced AP-1 activation
      in TPA-treated cells. These results provide insight into the biological actions
      of glycyrrhizin and the molecular basis for the development of new
      chemoprotective agents for cancer.

PMID- 11991253
TI  - Effects of extract of Ginkgo biloba leaves and its constituents on carcinogen
      metabolizing enzyme activities and glutathione levels in mouse liver.
AB  - The effects of a standardized extract of Ginkgo biloba L. leaves (EGb) and its
      terpene constituents, bilobalide and ginkgolides, on the activities of
      detoxification enzymes, i.e., glutathione S-transferases (GSTs) and DT
      diaphorase, and glutathione contents, were investigated in the mouse liver. Oral
      treatment with EGb (100-1,000 mg/kg) and bilobalide (10-30 mg/kg) once a day for
      4 days caused a dose-dependent elevation in GST activity. Ginkgolide A (30 mg/kg,
      for 4 days) also significantly elevated GST activity, whereas ginkgolide B and
      ginkgolide C at the same dose had no effects. EGb significantly increased the
      protein level of GST pi, and bilobalide significantly increased those of GST
      alpha and GST mu Moreover, EGb-treatment and bilobalide-treatment caused
      significant elevations in DT-diaphorase activity and in hepatic glutathione
      contents.

PMID- 11991254
TI  - Comparison of the antinociceptive effect of celecoxib, diclofenac and resveratrol
      in the formalin test.
AB  - The peripheral antinociceptive effect of the selective COX-2 inhibitor celecoxib
      in the formalin-induced inflammatory pain was compared with that of resveratrol
      (COX-1 inhibitor) and diclofenac (non-selective COX inhibitor). Rats received
      local pretreatment with saline, celecoxib, diclofenac or resveratrol followed by
      50 microl of either 1% or 5% formalin. Peripheral administration of celecoxib did
      not produce antinociception at either formalin concentration. In contrast,
      diclofenac and resveratrol produced a dose-dependent antinociceptive effect in
      the second phase of both 1% and 5% formalin test. The peripheral antinociception
      produced by diclofenac or resveratrol was due to a local action, as drug
      administration in the contralateral paw was ineffective. Results indicate that
      the selective COX-2 inhibitor celecoxib does not produce peripheral
      antinociception in formalin-induced inflammatory pain. In contrast, selective COX
      1 and non-selective COX inhibitors (resveratrol and diclofenac, respectively) are
      effective drugs in this model of pain.

PMID- 11991255
TI  - Gene expression profiling by cDNA array in human hepatoma cell line in response
      to cisplatin treatment.
AB  - Gene expression profiling with cDNA array allows simultaneous analysis of the
      gene expression pattern of a large number of genes and may enhance the
      investigation of the molecular mechanisms involved in the treatment of
      hepatocellular carcinoma with cisplatin. We used cDNA array technology to assess
      the gene expression profiles related to cell cycle regulation and apoptosis in
      human hepatoma Hep3B cells in response to cisplatin treatment. In Hep3B cells,
      apoptosis induced by cisplatin was p53-independent, and was associated with up
      regulation of cell cycle regulators, pro-apoptotic genes, growth receptors, and
      genes involved in signal transduction. These included p33ING1, c-Abl, Bax,
      insulin-like growth factor binding protein 3, Siva, cyclin D1, RhoA, and Raf-1.
      Down-regulation of cell cycle regulator CDC2 was observed. Semi-quantitative
      reverse transcription-polymerase chain reaction and/or Western blot analysis
      performed on seven of these genes confirmed their upregulation of gene
      expression. Such global analysis of the cytotoxic response to chemotherapeutic
      drugs may yield insight into the mechanisms of drug action and allow rational
      design of more effective treatment strategies.

PMID- 11991256
TI  - Induction of rcl, a novel growth-related gene by coptidis rhizoma in rat H4IIE
      cells.
AB  - Exposure of rat hepatoma cells to a low concentration of Coptidis Rhizoma reduces
      cell viability and probably induces apoptotic cell death. However, Coptidis
      Rhizoma treatment increased the expression of a putative c-myc-responsive gene
      rcl and could increase the activity of a transcription factor in inhibiting the
      growth of cancer cells. This increase was accompanied by an increment in the
      expression of mRNA for c-myc-responsive gene. The expression was analysed by PCR
      and confirmed by Northern blot analysis. The rcl expression level increases with
      the Coptidis Rhizoma concentration, and in the time-course study. The results
      suggest the expression of rcl is important to the fate of cell growth, since
      overexpression of the c-myc proto-oncogene cell proliferation, differentiation,
      and apoptosis can be regulated by the treatment of Coptidis rhizoma.
      Additionally, difference between overexpression of c-myc-responsive gene in the
      control suggested that this protein was responsible for the inhibitory effect of
      a transcriptional factor on cell growth. The results support the notion of rcl as
      an important antiapoptotic protein mediating sensitivity to Coptidis Rhizoma
      induction in cancer cells. rcl may play an important role during cellular
      proliferation and c-myc-mediated transformation.

PMID- 11991257
TI  - Up-regulation of central mu-opioid receptors in a model of hepatic
      encephalopathy: a potential mechanism for increased sensitivity to morphine in
      liver failure.
AB  - Increased GABA-mediated neurotransmission, reported to occur in hepatic
      encephalopathy (HE), is associated with a decrease in the release of Met
      enkephalin and the expression of its coding gene in the brain. Furthermore,
      patients with cirrhosis and a history of HE exhibit increased sensitivity to the
      neuroinhibitory effects of morphine. Thus, there is a rationale to study the
      status of the endogenous opioid system in HE. The aim of this study was to
      determine whether mu-opioid receptors in the brain are up-regulated in a well
      characterized model of HE. Binding parameters of mu-opioid receptors were derived
      by assaying the binding of the opiate agonist [3H]-tyr-D-Ala-Gly-N-Methyl-Phe-Gly
      ol (DAMGO) to brain membranes from rats with precisely defined stages of HE and
      control animals. The mean density of mu-opioid receptor sites (Bmax) in rats with
      stage II, III, and IV HE was 15, 29, and 33% higher, respectively, than the
      corresponding control value (p<0.01). In addition, the affinity of mu opioid
      receptors for the agonist (1/Kd) also increased with progression of HE (mean for
      stage IV HE vs. corresponding control mean, p<0.01). In conclusion, in liver
      failure, increased density and affinity of central mu-opioid receptors in the
      brain may: (i) be the basis for the documented increased sensitivity to opiate
      agonists; and (ii) occur as a consequence of increased GABAergic tone reducing
      neuronal synthesis and release of opioid agonist peptides.

PMID- 11991258
TI  - Release of non-mast cell histamine from rat aorta.
AB  - We previously reported that A23187 induces release of histamine from bovine
      intrapulmonary vein and provided pharmacological evidence against an involvement
      of mast cells as the source of histamine. This study was conducted to test more
      definitively the hypothesis that histamine is released from non-mast cell sources
      in blood vessels. The effects of A23187 on release of histamine were determined
      using rat aorta which does not contain mast cells. Aortic rings were mounted for
      recording of isometric tension, and following exposure to A23187 or vehicle,
      histamine in the bathing media was measured using enzyme immunoassay. A23187 (100
      nmol/l - 10 micromol/l) induced concentration-related release of histamine from
      rings with endothelium. The accumulation of histamine in the bathing media
      induced by 10 microM A23187 reached plateau at 60 min (6.2 +/- 1.1 pmol/mg) and
      was markedly and significantly higher than vehicle control (0.4 +/- 0.1 pmol/mg,
      p < 0.05). Destruction of endothelium significantly inhibited A23187-induced
      histamine release (5.5 +/- 1.5 pmol/mg with endothelium, 1.1 +/- 0.3 pmol/mg
      without endothelium, p < 0.05). The results demonstrate that A23187 induces
      release of histamine from rat aorta which does not contain mast cells and that
      the release of histamine is largely dependent on the presence of endothelium.

PMID- 11991259
TI  - The impact of duplex scanning in phlebology.
AB  - Chronic venous disease (CVD) is a tremendous medical and economic burden on
      society. In the past two decades the use of duplex ultrasound has emerged as the
      diagnostic method of choice for the diagnosis and management of CVD. In this
      article, we describe the specific techniques used in the assessment of the
      superficial, perforating, and deep venous systems. We also discuss the methods of
      ulcer bed and chronic obstruction evaluation. The contributions of the duplex
      ultrasound to the understanding of the pathophysiology and improvement of
      treatments for chronic venous disease are reviewed.

PMID- 11991260
TI  - Effective use of the glabella skin as a donor site for nasal tip grafts.

PMID- 11991261
TI  - Treatment for a large full-thickness defect in a hostile tissue healing
      environment.

PMID- 11991262
TI  - Sclerosing foam in the treatment of varicose veins and telangiectases: history
      and analysis of safety and complications.
AB  - OBJECTIVE: To review the use of sclerosing foam in the treatment of varicose
      veins, to describe the different techniques of foam preparation, and to report
      the complications of our 3-year experience with this treatment. METHOD: From
      November 1997 to the end of October 2000, 453 patients were treated with a
      sclerosing foam for large, medium, and minor varicosities with sodium
      tetradecylsulfate (STS) or polidocanol (POL). A first group of 257 patients (90
      for minor varicosities and 167 for medium to large veins) received a sclerosing
      foam according to the Monfreux technique. From December 1999 to October 2000, 196
      patients were treated with a sclerosing foam prepared according to Tessari's
      method (36 for minor size veins or teleangectasias and 170 for medium-large
      veins). Every patient was studied with (color-flow) duplex scanning before and
      after the treatment and large vein injections were administered under duplex
      guide. RESULTS: The immediate success rate was 88.1% in the first group for the
      medium-large veins. In the same districts we registered an early success rate in
      93.3% for the patients treated with the Tessari's method. The complication rate
      (mostly minor complications) was 8.5% in the first group and 7.1% in the second
      group. CONCLUSION: The use of sclerosing foam may become an established therapy
      in the treatment of varicose veins with a high success rate, low cost, and low
      major complication rate. According to our actual experience and knowledge, the
      safe amount of foam should not exceed the 3-ml limit, but further advancements
      could come from standardization of the foam preparation technique.

PMID- 11991263
TI  - Advances in laser surgery for leg veins: bimodal wavelength approach to lower
      extremity vessels, new cooling techniques, and longer pulse durations.

PMID- 11991264
TI  - The utilization of a new yellow light laser (578 nm) for the treatment of class I
      red telangiectasia of the lower extremities.
AB  - BACKGROUND: A dual-wavelength approach is necessary in order to achieve
      consistent results when utilizing lasers and intense pulsed light sources to
      treat red and blue lower extremity vessels. In this regard, short-wavelength
      technologies (500-800 nm) may be employed to treat red telangiectasia of less
      than 2 mm on the lower extremities. OBJECTIVE: To demonstrate a new yellow light
      laser utilizing a copper bromide medium and its potential efficacy in the
      treatment of red lower extremity telangiectasia of less than 2 mm. METHODS: Forty
      six women (mean age 37 years) were treated in two private practice settings with
      a 578 nm yellow light laser with a circulating cooling window (1-4 degrees C).
      Class I red telangiectases of the thighs 1.5 mm or less in diameter were
      considered for treatment. Patients were treated with up to three treatments at 6
      week intervals on a 5 cm2 surgical area of vessels utilizing a fluence of 50-55
      J/cm2. Results were analyzed by macrophotographic imaging, double-blinded
      observer evaluation/optical chromatography, and a patient evaluation scale.
      RESULTS: An average of 1.7 patient treatment sessions produced significant
      clearing of 75-100% in 71.8% of patients. The mean erythema index showed
      significant lightening (51-65a+) in the study population. Finally, 76.1% of
      patients reported great satisfaction with the results of their treatment session.
      CONCLUSION: A new 578 nm copper bromide (CuBr) yellow light laser produces
      excellent results in eradicating red telangiectases of the lower extremities that
      are less than 2 mm in diameter.

PMID- 11991265
TI  - Advances in venous surgery: SEPS and phlebectomy for chronic venous
      insufficiency.
AB  - Chronic venous insufficiency (CVI) and its complications of chronic pain,
      intractable ulceration, and infection are important conditions to treat by modern
      surgical techniques. As early as the 1930s, perforating veins with outward flow
      were implicated in the pathogenesis of this condition. Recognition that such
      outward flow promotes leukocyte adhesion and activation as the principal
      microcirculatory cause for the cutaneous changes has explained the importance of
      perforating vein interruption? Because of disability of CVI, surgeons and
      patients reluctantly tolerated the open Linton perforator interruption operation
      with its morbid knee-to-ankle incisions. It was tolerated because it worked.
      Modifications to reduce the morbidity of the procedure eliminated two of the
      three incisions used in the explorations of the 1930s. Other modifications such
      as DePalma's modification of the incisions further reduced wound complications.
      However, the most significant surgical alteration was to utilize the endoscopic
      techniques introduced in Europe by Fischer and Hauer. Very quickly it was obvious
      that the endoscopic technique minimized postoperative complications. Application
      of endoscopic perforator interruption to varicose vein surgery validated the
      safety of the procedure but did not contribute to knowledge about treating CVI.

PMID- 11991266
TI  - Closure of the greater saphenous vein with endoluminal radiofrequency thermal
      heating of the vein wall in combination with ambulatory phlebectomy: 50 patients
      with more than 6-month follow-up.
AB  - BACKGROUND: Incompetence of the saphenofemoral junction (SFJ) with reflux into
      the greater saphenous vein (GSV) is one cause of chronic venous hypertension that
      may lead to the development of varicose and telangiectatic leg veins. OBJECTIVE:
      To evaluate with long-term follow-up a novel method for closing the incompetent
      GSV at its junction with the femoral vein through an endoluminal approach.
      METHODS: Fifty patient legs with reflux at the SFJ into the GSV were treated with
      radiofrequency (RF) heating of the vein wall through an endoluminal catheter.
      Patients were evaluated at 6, 9, 12, and 18-24 months to determine treatment
      efficacy as well as adverse sequelae. RESULTS: Nine patients could not return for
      evaluation after 3 months. The remaining 41 patient legs were evaluated. Sixty
      eight percent of treated legs achieved complete closure of the SFJ and GSV.
      Twenty-two percent of legs had an open GSV without reflux. Three patients (four
      legs) (10%) had an open and refluxing GSV. Three of 41 legs had recurrent
      varicose veins. Only 1 of 41 legs had recurrent symptoms. Complete treatment took
      an average of 20 minutes. Adverse sequelae were minimal, with 28 legs showing
      purpura less than 2 weeks, 5 legs with erythema less than 1 week, and 8 legs with
      an indurated fibrous cord lasting for up to 6 months posttreatment. CONCLUSION:
      Endoluminal RF thermal heating of an incompetent GSV has been shown to be easily
      accomplished and efficacious throughout the 24-month-follow-up period.

PMID- 11991267
TI  - Multifocal pull-through endovascular cannulation technique of ambulatory
      phlebectomy.
AB  - BACKGROUND: New treatment indications and improved technique modifications have
      made ambulatory phlebectomy increasingly popular in the management of
      intermediate and large truncal varicosities. OBJECTIVE: To describe a new
      technique of ambulatory phlebectomy that combines a multifocal incisional and
      endovascular cannulation approach. This study compares this newly described
      technique to the previously described "pulling maneuver." METHODS: A double
      blinded study consisting of 50 patients who were treated by the conventional
      pulling maneuver and 50 patients treated by the multifocal pull-through
      endovascular cannulation technique was conducted. This newly described technique
      was compared to the previously described "pulling maneuver" in terms of length of
      vessel avulsed per puncture site, intraoperative time, and complication profile.
      An average of 20 cm of diseased venous segment was avulsed in each patient
      subgroup. Results were analyzed utilizing the paired t test (P < .05). RESULTS: A
      36% increase in vessel avulsion length per puncture site was achieved in the
      endovascular pull-through cannulation subgroup compared to the classic pulling
      maneuver population. The number of puncture sites in the 20 cm segment of veins
      in the classic pulling maneuver population was 4.50 versus 3.04 in the multifocal
      pull-through subgroup. The mean operative time was 20% less in the pull-through
      cannulation population versus the classic pulling technique. Side effect profiles
      were similar in the two patient subgroups. CONCLUSION: The multifocal pull
      through cannulation technique allows extraction of large segments of diseases
      varicose veins with fewer puncture sites in a more efficient fashion than
      previously described techniques.

PMID- 11991268
TI  - Controlled radiofrequency endovenous occlusion using a unique radiofrequency
      catheter under duplex guidance to eliminate saphenous varicose vein reflux: a 2
      year follow-up.
AB  - BACKGROUND: Saphenous vein reflux is often the underlying anatomic cause of
      varicose veins. It is necessary to eliminate this reflux originating at the
      saphenofemoral junction (SFJ) to treat the resultant varicose veins. OBJECTIVE:
      To report 2-year follow-up results after closing the incompetent greater
      saphenous vein starting from its junction (SFJ) with the femoral vein using
      radiofrequency (RF) endoluminal ablation. METHODS: One hundred and forty
      incompetent greater saphenous veins from 120 patients with an incompetent SFJ and
      large painful varicosities were treated. Patients were evaluated clinically and
      with duplex ultrasound at 1 week, 6 weeks, 6 months, 12 months, and 24 months to
      determine treatment efficacy as well as adverse sequelae. RESULTS: Vein
      occlusion, defined as the absence of any duplex ultrasound-determined flow, was
      successfully achieved in 137 of 140 (98%) scanned veins at 1-week follow-up. At
      the 12-month follow-up, none of the treated patients developed recanalization
      that was not seen at 6 weeks, with a successful outcome in 90%. At the 24 month
      follow-up, 19 of 21 patients had complete disappearance of the treated saphenous
      vein, for a success rate of 90%. Side effects were minimal, and no skin burns or
      thromboses were observed. CONCLUSION: RF endovenous occlusion allows patients to
      obtain treatment with the positive attributes of surgery, that is, a single
      treatment and low rate of recurrent reflux, but without the morbidity, need for
      general anesthesia, or extensive convalescence associated with vein stripping and
      ligation surgery. Patient satisfaction was routinely achieved, with 98% of
      patients indicating a willingness to recommend the RF endovascular procedure to a
      friend or family member.

PMID- 11991269
TI  - Removal of blue periocular lower eyelid veins by ambulatory phlebectomy.
AB  - BACKGROUND: Prominent periocular veins, primarily of the lower eyelid, are a
      relatively frequent cosmetic problem. Reported treatment techniques have included
      electrosurgical, sclerotherapy, and longer-wavelength lasers. OBJECTIVE:
      Ambulatory phlebectomy can be performed on reticular veins of the leg. This
      technique has been applied over the past few years to periocular reticular veins
      in order to observe the results and side effects. METHODS: Using a hook
      specifically designed for reticular veins, we treated 10 patients who had larger
      reticular periocular eyelid veins. One or several punctures with an 18-gauge
      needle were made in the center of the targeted length of vein. The reticular vein
      was then gently dissected by undermining with the stem of the Ramelet phlebectomy
      hook. RESULTS: All 10 patients tolerated the procedure well. In 8 of 10 patients
      there was complete elimination with a single procedure. Surprisingly, no
      significant hematoma was seen in any patient, although two patients had a small
      hematoma lasting less than 1 week. Two patients had only partial success, as a
      small segment of vein was difficult to extract. This was eliminated with a second
      phlebectomy performed 2 months later in both cases. Edema that is usually seen
      after sclerotherapy was not noted in any of these patients. CONCLUSIONS:
      Ambulatory phlebectomy appears to be a safe and effective means of permanently
      eradicating periocular veins.

PMID- 11991270
TI  - Sclerotherapy of reticular and telangiectatic veins of the face, hands, and
      chest.
AB  - BACKGROUND: Prominent tortuous veins of the face and hands may result from the
      process of aging and constitute a source of distress for many patients. Marked
      telangiectases of the chest and face are similarly distressing to some patients.
      OBJECTIVE: To determine the safety and efficacy of sclerotherapy for
      telangiectatic veins of the face and chest and varicose veins of the hands.
      METHODS: Twenty facial telangiectases and tortuous veins in 14 patients and 20
      total facial sites were treated with sclerotherapy. Patients did not suffer from
      collagen vascular diseases, had no chronic illnesses, and were thoroughly
      informed of the strictly cosmetic nature of the procedure. A hyperosmolar
      sclerosant was used in 16 of 20 sites and the remaining 4 sites were treated with
      a detergent sclerosant (polidocanol 0.5-0.75%). The follow-up period ranged from
      9 months to 15 years. Similarly the varicose veins of 14 hands in seven patients
      were treated with sclerotherapy using a detergent sclerosant [sodium tetradecyl
      sulfate (STS)] at various concentrations (1-3%). The follow-up period ranged from
      1 to 6.5 years. Tortuous veins and telangiectases on the chest of three patients
      were treated with either STS 0.25-0.50% or polidocanol 0.75% with a follow-up of
      2-9 years. RESULTS: Tortuous facial veins and telangiectases had a mean
      improvement of 70%, with 11 of 20 sites showing a 90-100% improvement. Hand
      varicosities had a mean improvement of 97.8%, and all sites showed a 90-100%
      resolution of varicosities. Finally, the tortuous veins and telangiectases of the
      chest improved by 50-100% with sclerotherapy. Only minimal to moderate
      telangiectatic matting was observed in two patients (one in the lateral canthal
      area and one near the treatment site of chest reticular veins). No ulceration or
      hyperpigmentation occurred long term in facial or hand veins. One patient
      developed an arterial ulceration on the left lateral breast. CONCLUSION:
      Sclerotherapy of varicose and telangiectatic veins of the face, hands, and chest
      can be safe and effective. Care must be given to sclerotherapy in the chest area,
      particularly the breast.

PMID- 11991271
TI  - Treatment of varicose and telangiectatic leg veins: double-blind prospective
      comparative trial between aethoxyskerol and sotradecol.
AB  - BACKGROUND: One hundred twenty-nine patients were treated with either polidocanol
      (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse
      sequelae of each agent. OBJECTIVE: To determine the safety and efficacy of two
      sclerosing solutions. METHODS: Each patient's leg veins that did not have
      incompetence from the saphenofemoral junction (SFJ) were divided into three
      categories by size (<1 mm, 1-3 mm, 3-6 mm). Each leg was randomly treated with
      either 0.25%, 0.5%, or 1.5% of STS or 0.5%, 1.0%, or 3% of POL respective of
      size. An independent, three-panel, blindly randomized photographic examination
      was obtained pretreatment and at 4 and 16 weeks. Patient satisfaction index and
      overall clinical improvement assessment were also obtained. RESULTS: All patients
      had an average of 70% improvement and were 70-72% satisfied in all vein
      categories treated with either solution. There was no significant difference in
      adverse effects between each group except for a decrease in ulcerations and
      swelling in the POL group. CONCLUSION: Both STS and POL are safe and effective
      sclerosing solutions for varicose and telangiectatic leg veins.

PMID- 11991272
TI  - Comparison of endovenous radiofrequency versus 810 nm diode laser occlusion of
      large veins in an animal model.
AB  - BACKGROUND: Endovenous occlusion using radiofrequency (RF) energy has been shown
      to be effective for the elimination of sapheno-femoral reflux and subsequent
      elimination of varicose veins. Recently, endovenous laser occlusion has been
      introduced with initial clinical reports indicating effective treatment for
      varicose veins. However, in our practice we note increased peri-operative
      hematoma and tenderness with the laser. Little is known regarding the mechanism
      of action of this new laser vein therapy. OBJECTIVE: To better understand the
      mechanism of action of endovenous laser vs. the endovenous RF procedure in the
      jugular vein of the goat model. METHODS: A bilateral comparison was performed
      using 810 nm diode laser transmitted by a bare-tipped optical fiber vs. the RF
      delivery by engineered electrodes with a temperature feedback loop using a
      thermocouple (Closure procedure) in three goat jugular veins. Immediate and one
      week results were studied radiographically and histologically. Temperature
      measurements during laser treatment were performed by using an array of up to
      five thermocouples, spaced 2 mm apart, placed adjacent to a laser fiber tip
      during goat jugular vein treatment. RESULTS: Immediate findings showed that 100%
      of the laser-treated veins showed perforations by histologic examination and
      immediate contrast fluoroscopy. The RF-treated side showed immediate constriction
      with maintenance of contrast material within the vein lumen and no perforations.
      The difference in acute vein shrinkage was also dramatic as laser treatments
      resulted in vein shrinkage of 26%, while RF-treated veins showed a 77% acute
      reduction in diameter. At one week, extravasated blood that leaked into the
      surrounding tissue of laser treated veins acutely, continued to occupy space and
      impinge on surrounding structures including nerves. For the laser treatment, the
      highest average temperature was 729 degrees C (peak temperature 1334 degrees C)
      observed flush with the laser fiber tip, while the temperature feedback mechanism
      of the RF method maintains temperatures at the electrodes of 85 degrees C.
      CONCLUSION: Vein perforations, extremely high intravascular temperatures, failure
      to cause significant collagen shrinkage, and intact endothelium in an animal
      model justify a closer look at the human clinical application of the 810 nm
      endovenous laser technique. Extravasated blood impinging on adjacent structures
      may theoretically lead to increased peri-operative hematoma and tenderness.
      Further study and clinical investigation is warranted.

PMID- 11991273
TI  - Compression therapy.
AB  - Compression therapy, either active or passive, is the cornerstone of treatment
      for all venous and lymphatic disorders. Its major limitations are poor patient
      compliance, difficulty to apply in the elderly, and insufficient knowledge and
      skill in the majority of physicians. New modalities, such as four-layer bandage,
      tubular gradient compression, or new textile technologies, may secure a better
      application in difficult cases such as leg ulcers.

PMID- 11991274
TI  - Auricular reconstruction of helical rim defects: wedge resection revisited.
AB  - Auricular reconstruction of an acquired helical rim defect is a clinical
      situation commonly encountered by dermatologic surgeons. Wedge resection is a
      simple but effective method for repairing such helical rim defects. This is a
      review of the wedge resection, outlining its indications, limitations, surgical
      technique, postoperative care, and pitfalls.

PMID- 11991275
TI  - Prevention of temporal alopecia following rhytidectomy: the prophylactic use of
      minoxidil. A study of 60 patients.
AB  - BACKGROUND: Temporal hair loss that results from traumatized hair follicles
      following rhytidectomy is an unsightly complication that can distress both the
      patient and the operating surgeon. Topical minoxidil is a proven therapy for
      androgenic alopecia and female senile alopecia. It has also been found to be
      useful in preventing the hair loss that commonly follows hair transplantation.
      OBJECTIVE: To analyze through a retrospective study the effect of topical
      minoxidil on the incidence of temporal hair loss following facelift procedures.
      To our knowledge this is the first study to investigate the role of minoxidil in
      preventing post-rhytidectomy temporal alopecia. METHODS: The charts of 60 women
      with a mean age of 58 years who underwent primary cervicofacial rhytidectomy were
      studied. Either a standard SMAS/flap technique or pliation was done in all cases.
      Each patient received either 2% or 5% topical minoxidil for 2 weeks before
      surgery and for 4 weeks after surgery, with a 5-day break period beginning on the
      day of surgery. Patients were monitored for complications immediately
      postoperatively and in 3-6 months of follow-up. RESULTS: Almost 80% of the
      patients underwent SMAS/flap procedures. Transient temporal alopecia was noted in
      only one patient, 6 weeks after discontinuing minoxidil. This resolved within 4
      weeks of its reintroduction. The only other complications noted included minor
      hematomas (3.3%), skin slough/infection (1.7%), minor transient and localized
      edema (8.3%), minor ecchymosis (1.7%), a unilateral neuropraxia of the buccal
      nerve lasting 3 months (1.7%), and a minor temporary unilateral skin depression
      (1.7%). Side effects of minoxidil were not observed. CONCLUSION: On comparing our
      findings to results of larger rhytidectomy series in which minoxidil was not used
      prophylactically, and our experience before using minoxidil, we conclude that
      minoxidil plays a role in effectively preventing the temporal hair loss that
      occurs following primary cervicofacial rhytidectomies. We also found that
      minoxidil did not negatively impact on the risk of hematoma formation, skin
      necrosis, edema, or ecchymosis. Side effects of minoxidil did not present a
      problem.

PMID- 11991276
TI  - Cerebriform giant melanocytic nevus of the scalp: report of two cases with
      different surgical approaches.
AB  - Cerebriform giant melanocytic nevus of the scalp is an extremely rare
      malformation. Clinical appearance with maceration and fetor within the crypts and
      the risk of malignant transformation may require surgical therapy. We report two
      cases with different methods of surgical management. A 27-year-old woman noticed
      a swelling of the parietal scalp that developed over a period of 4 years into a
      gyrus-like tumor measuring 12 cm x 18 cm. The crypts between the gyri could not
      be inspected. Serial excisions under subcutaneous infusion anesthesia were
      performed to reduce the size of the nevus and to flatten the surface of the
      scalp. The second patient, a 26-year-old man, demonstrated a giant 10 cm x 10 cm
      cerebriform nevus on the occiput. The nevus also contained areas of fetid
      maceration. After implanting a tissue expander under general anesthesia the nevus
      was excised. The defect was closed using a rotation flap.

PMID- 11991277
TI  - Clinical and economic outcomes with graftskin for hard-to-heal venous leg ulcers:
      a single-center experience.

PMID- 11991278
TI  - Hidradenitis suppurativa and squamous cell carcinoma.
AB  - BACKGROUND: Hidradenitis suppurativa is a recurrent, chronic inflammatory disease
      with complications such as abscesses and sinus tract formations, fistulization,
      and scarring. Squamous cell carcinoma is rare, and is the most serious
      complication. OBJECTIVE: To present the evolution of squamous cell carcinoma in
      long-term hidradenitis suppurativa. METHODS: Case report and literature review.
      CONCLUSION: Many conservative therapies have no or minimal effect in perineal
      hidradenitis suppurativa. Therefore surgical excision must be considered in the
      early stages of the disease at this region to prevent further complications.

PMID- 11991279
TI  - A visit to the office of Dr. Stefano Ricci.
AB  - The author is a phlebologist who practices his profession in an office-based
      environment. The surgical ambiance and practices are described. In this age when
      outpatient surgical procedures are commonplace, it is hoped that the information
      contained in this article will facilitate the care of patients with varicose
      veins.

PMID- 11991280
TI  - Areolar cosmetic tattoo ink darkening: a complication of Q-switched alexandrite
      laser treatment.
AB  - BACKGROUND AND OBJECTIVE: Medical tattooing of the areola is widely performed in
      Korea. However, cosmetic tattoos containing flesh-tone, purple-red, and yellow
      dyes are sometimes resistant to Q-switched laser and may even become darker.
      METHOD: Two Korean women in their 30s who had a mastectomy got light brown to red
      areolar medical tattoos but they were not satisfied with the shape and size of
      the tattoos. They underwent Q-switched alexandrite laser treatment with a 3 mm
      collimated beam at fluences of 7.5-8 J/cm2 in order to trim the irregular contour
      and reduce the diameter of the tattoos. RESULTS: Within 5 minutes a dark gray to
      black discoloration of the treated area was evident and remained dark for 6
      weeks. Improvement was not noted after two further Q-switched Nd:YAG laser
      treatments. CONCLUSION: Medical areolar tattoos should be approached with extra
      caution when attempting their removal with high-energy pulsed lasers such as Q
      switched alexandrite laser and a small test site should be performed prior to
      treatment.

PMID- 11991281
TI  - Concomitant use of a high-energy pulsed CO2 laser and a long-pulsed (810 nm)
      diode laser for squamous cell carcinoma in situ.

PMID- 11991282
TI  - Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis.
AB  - BACKGROUND: Eosinophils and T lymphocytes represent constant features in the
      airways of subjects with exacerbated chronic bronchitis. Eotaxin is the most
      potent and selective eosinophil chemoattractant which can also attracts
      lymphocytes. The aim of the study was to evaluate the expression of eotaxin and
      its receptor, CCR3, in bronchial airways during exacerbation of chronic
      bronchitis. METHODS: By immunohistochemistry we studied eotaxin and CCR3
      expression in the lamina propria of 14 subjects with acute exacerbation of
      chronic bronchitis. 20 asthmatics, and 8 healthy subjects. We determined the cell
      types expressing the CCR3 receptor by colocalization experiments. We finally
      studied the relationship between eotaxin and CCR3 and eosinophils and T
      lymphocytes. RESULTS: The number of eotaxin+ and CCR3+ cells was significantly
      higher in exacerbated chronic bronchitis (P<0.003 and P<0.002) and asthma
      (P<0.002 and P<0.0001) when compared to healthy subjects. CCR3 was mainly
      expressed by eosinophils and to a lesser extent by CD4+ and CD8+ lymphocytes. In
      exacerbated chronic bronchitis the number of CCR3+ cells was strongly correlated
      to the number of eosinophils (P<0.0002. r=0.85) and to the number of CD4+
      lymphocytes (P<0.05, r=0.57). CONCLUSION: Our study suggests that eotaxin and
      CCR3 are up-regulated and could be involved in the eosinophil and CD4+ lymphocyte
      recruitment into the airways which occur during acute exacerbations of chronic
      bronchitis.

PMID- 11991283
TI  - Antigen-presenting cells and tolerance induction.
AB  - T cell tolerance induction to foreign and self-antigens has occupied research
      since the beginning of the understanding of the immune system. Much controversy
      still exists on this question even though new methods became available to
      investigate immunoregulatory mechanisms. Antigen-presenting cells play a pivotal
      role in transferring information from the periphery of the organism to lymphoid
      organs. There, they initiate not only the activation of naive T cells but seem to
      deliver important signals which result in T cell unresponsiveness with antigen
      specific tolerance induction.

PMID- 11991284
TI  - Low-dose local nasal immunotherapy in children with perennial allergic rhinitis
      due to Dermatophagoides.
AB  - BACKGROUND: Allergen specific immunotherapy was known to be useful in the
      treatment of respiratory allergic disease. Local nasal immunotherapy (LNIT)
      offers advantages such as a good efficacy/safety ratio and a more convenient
      allergen delivery. The aim of this study was to assess the safety and clinical
      efficacy of a modified scheduling of LNIT in 32 children with allergic rhinitis
      due to Dermatophagoides. METHODS: A multicentre, randomized, double-blind placebo
      controlled study carried out for two years, with a modified schedule of LNIT
      treatment: a build-up phase at increasing dosages from 2.5 AU to 80 AU and a
      maintenance period at low dosage (80 AU) once a week. Symptom and medication
      scores. threshold dose with specific nasal provocation test (NPT) and
      immunological parameters (IgE and IgG4) were evaluated. RESULTS: No important
      local or systemic side-effects were observed in children who completed the study.
      Compared to placebo, the active treatment group showed significant improvement in
      rhinitis symptoms and a reduction of drug consumption after 18 months of LNIT.
      These results were confirmed by a significant reduction of allergen specific
      nasal reactivity. Serum and nasal specific IgE and IgG4 did not show any
      difference in the two groups. CONCLUSIONS: The safety and clinical efficacy of
      low-dose LNIT suggests that this therapy may be useful in the treatment of
      allergic rhinitis disease in children.

PMID- 11991285
TI  - Monoclonal antibodies to recombinant Der f 2 and development of a two-site ELISA
      sensitive to major Der f 2 isoallergen in Korea.
AB  - BACKGROUND: Der f 2 is a major sensitizing allergen in patients allergic to house
      dust mites worldwide. Isoforms of Der f 2 have been reported and are known to
      have different antigenicities. The aim of this study was to facilitate antigenic
      analysis and to develop an improved method for the detection of Der f 2
      isoallergen, which is prevalent in Korea. METHODS: A two-site ELISA was developed
      with monoclonal antibodies (mAbs) which were produced against recombinant Der f 2
      (rDer f 2) and applied to assess Der f 2 in bedding samples. RESULTS: A major
      isoform of Der f 2, found in Korea, was found to have amino acid variations
      especially at position 100 from lysine to glutamic acid, which is known to reduce
      significantly the binding affinity of mAbs when used to assess group 2 allergens.
      The detection limit of the developed two-site ELISA was determined to be about 8
      ng/ml with rDer f 2 and 1 microg/ml with Derntatophagoides farinae crude extract.
      The average amount of Der f 2 in dust obtained from bedding samples from 89 homes
      in Seoul was estimated to be 25.61+/-10.70 microg/g dust. CONCLUSIONS: Assays
      using mAbs for rDer f 2 could be useful for the assessment of environmental
      allergen exposure and mAbs could be used to further characterize the isoallergens
      of Der f 2.

PMID- 11991286
TI  - Sensitization to sunflower pollen and lung functions in sunflower processing
      workers.
AB  - BACKGROUND: This study aimed to investigate whether exposure to sunflower pollen
      (Helianthus annuus) increases both sensitization and respiratory symptoms, and
      whether or not it affects lung functions in sunflower processing workers.
      METHODS: The largest sunflower processing factories in the Thrace region of
      Turkey participated in this study. Workers from the units directly exposed to
      sunflower seed enrolled as the study group (n = 102) and workers who were not
      directly exposed to Helianthus annuus pollen (n = 102) were the control group.
      Detailed questionnaires covering respiratory and allergic symptoms were
      completed, and skin prick tests and lung function tests were performed. RESULTS:
      We found a very high rate (23.5%) of sensitization to Helianthus annuus in the
      study group compared to the controls (P<0.001). Logistic regression analysis
      showed that the risk of sensitization to H. annuus was increased 4.7-fold (odds
      ratio = 4.17, 95%) confidence interval = 1.3-16.7) if subjects were exposed to
      sunflower pollen in the workplace. While asthmatic symptoms and allergic skin
      diseases were not different between the two groups, workers in the study group
      had a higher rate of allergic rhinitis and conjunctivitis (P<0.05). We found that
      pulmonary function was significantly impaired in the study group (P<0.01). Using
      a multivariate analysis model, inclusion in the study group was found to be a
      predictive factor for impairment of lung function (P=0.002). CONCLUSIONS: We
      conclude that sunflower pollen has high allergenic potential, especially when
      there is close contact, and exposure to sunflower pollen in the workplace can
      result in impairment in lung function.

PMID- 11991287
TI  - Olive pollen allergen Ole e 8: identification in mature pollen and presence of
      Ole e 8-like proteins in different pollens.
AB  - In a first approach, Ole e 8, a novel Ca2+-binding protein from olive pollen, was
      cloned and produced in Escherichia coli. We have obtained the natural form of Ole
      e 8 (nOle e 8) from the pollen and examined its immunologic equivalence with its
      recombinant form (rOle e 8). Size exclusion chromatography and a phenyl-Sepharose
      CL-4B affinity column were used to obtain nOle e 8 from the olive pollen.
      Inhibition assays by immunoblotting, using rOle e 8-specific rabbit antiserum,
      were performed to analyze the immunologic equivalence between the natural and the
      recombinant allergen, as well as to detect its presence in other pollens.
      Recombinant and natural Ole e 8 resulted immunologically equivalents, since they
      completely inhibited the IgG binding of the polyclonal antiserum to each other.
      Ole e 8-like proteins were detected in Oleaceae and Juniperus communis pollen,
      and might contribute to cross-reactivity processes between taxonomically related
      pollens.

PMID- 11991288
TI  - Do only live larvae cause Anisakis simplex sensitization?

PMID- 11991289
TI  - General considerations for skin test procedures in the diagnosis of drug
      hypersensitivity.

PMID- 11991290
TI  - Allergic urticaria from tonic water.

PMID- 11991291
TI  - Immediate hypersensitivity due to pseudoephedrine.

PMID- 11991292
TI  - Selective hypersensitivity to pidolate.

PMID- 11991293
TI  - Urticaria to carisoprodol.

PMID- 11991294
TI  - FDE to macrolides.

PMID- 11991295
TI  - Immediate pressure urticaria.

PMID- 11991296
TI  - Exanthema with eosinopenia.

PMID- 11991297
TI  - Mites in Madrid.

PMID- 11991298
TI  - Allergenic pollens in south-east Spain.

PMID- 11991299
TI  - Hypersensitivity to icodextrin.

PMID- 11991300
TI  - Cow's milk allergy--a matter of fat.

PMID- 11991301
TI  - Allergenic similarities of 2S albumins.

PMID- 11991302
TI  - Interleukines in nasal lavage.

PMID- 11991303
TI  - Immunoglobulin G antibodies to moulds in school-children from moisture problem
      schools.
AB  - BACKGROUND: The purpose of the present study was to evaluate mould-specific
      immunoglobulin G (IgG) antibodies in children exposed to moisture and mould
      problems in their school, and the association between IgG antibodies and mould
      allergy, active or passive smoking and respiratory symptoms. METHODS: IgG
      antibodies were studied to 24 moulds in 93 children from three moisture problem
      schools and in 33 children from a reference school. The antibodies were measured
      by enzyme-linked immunosorbent assay and compared to positive adult sera.
      RESULTS: There were no significant differences in mould-specific IgG
      concentrations between exposed and non-exposed school-children. Antibodies to
      moulds common in moisture damaged buildings were associated with allergic
      diseases, as well as with mould-specific immunoglobulin E (IgE) or skin prick
      test (SPT) findings. Aspergillus fumigatus and A. versicolor were the moulds with
      the most consistent findings. Active and passive smoking were associated with low
      levels of antibodies to many moulds. Though the association between asthma,
      wheezing or cough symptoms, and IgG to moulds was not significant, 7 (39%) of the
      18 children with multiple (> 7) elevated IgG findings suffered from asthma or
      wheezing. CONCLUSIONS: Allergy was, but asthma was not, associated with IgG
      antibodies to the moulds that can be found in moisture damaged buildings.
      However, no association was found between IgG antibodies to moulds and exposure
      to moisture and moulds in school.

PMID- 11991304
TI  - A case of complex odontoma associated with an impacted lower deciduous second
      molar and analysis of the 107 odontomas.
AB  - OBJECTIVE: Odontoma is a comparatively common odontogenic tumor, and it may lead
      to interference with the eruption of its associated tooth. Odontomas are mostly
      associated with permanent teeth, and they are rarely associated with deciduous
      teeth. The purpose of this report is to analyze 107 odontomas and to present a
      case of complex odontoma associated with a lower deciduous second molar. SUBJECT
      AND METHODS: The 106 cases were analyzed with regard to the following parameters:
      age, gender, location, erupted teeth, congenital missing teeth, radiological
      features, histopathological features and prognosis. RESULTS: Of the 106 cases, 41
      were complex odontoma, 62 were compound odontoma, and three were immature
      odontoma. Compound odontoma had a predilection for the anterior. Complex odontoma
      occurred more often at the mandible. CONCLUSION: Odontoma located above the tooth
      crown of lower deciduous molar did not behave clinically different from that
      associated with permanent tooth. An odontoma could be related with a
      supernumerary tooth or a missing tooth. If odontomas, which interfered with tooth
      eruption, were extirpated early, the impacted teeth would probably erupt normally
      and be normal in shape.

PMID- 11991305
TI  - Segmental odontomaxillary dysplasia: clinical, radiological and histological
      aspects of four cases.
AB  - Segmental odontomaxillary dysplasia (SOD) is a rare developmental disorder of the
      maxilla, primarily involving the posterior part of the maxilla. Clinically, the
      disorder is often diagnosed in early childhood due to a unilateral buccolingual
      expansion of the posterior alveolar process, gingival enlargement, absence of one
      or both premolars in the affected region, delayed eruption of the adjacent teeth
      and malformations of the primary molars. In this report, four patients with SOD
      are described. The findings were similar to earlier reports, but for the first
      time an ipsilateral rough erythema on the skin in two of the subjects is
      reported.

PMID- 11991306
TI  - Solitary fibrous tumour of the mouth: report of two cases involving the tongue
      and cheek.
AB  - We describe two additional cases of solitary fibrous tumour (SFT) affecting the
      mouth. SFT is very uncommon in the oral cavity and we found only 14 cases
      reported in the literature. Our two cases were well circumscribed, slow growing
      tumours that, after surgical removal, did not recur. Case 1 was a 3 cm nodule on
      the right cheek. Hypo and hypercellular adjacent areas were mainly patternless,
      and the stroma was formed by thin collagen fibrils. Case 2 was a 4.8 cm mass in
      the anterior portion of the tongue. Microscopically it was formed by spindle
      cells embedded in a vascularized sclerotic collagen matrix. Some areas were
      hypercellular with scarce collagen fibrils. The immunohistochemical findings were
      similar in both cases, with strong immunoreactivity for vimentin, CD34, bcl-2,
      focal positivity for Ki-67 and negativity for other immunomarkers. Based on these
      clinical, microscopical and immunohistochemical features the final diagnosis of
      these two cases was SFT. Diagnosis of SFT is difficult and, although uncommon, it
      should be considered in the differential diagnosis of oral soft tissue tumours.

PMID- 11991307
TI  - Saliva as a diagnostic fluid.
AB  - In the last 10 years, the use of saliva as a diagnostic fluid has become somewhat
      of a translational research success story. Technologies are now available
      enabling saliva to be used to diagnose disease and predict disease progression.
      This review describes some important recent advances in salivary diagnostics and
      barriers to application and advancement. This review will also stimulate future
      research activity.

PMID- 11991308
TI  - Diagnosing, managing, and preventing salivary gland disorders.

PMID- 11991309
TI  - Changes in the prevalence of HIV-associated mucosal disease at a dedicated clinic
      over 7 years.
AB  - OBJECTIVE: To investigate changes in the prevalence of mucosal disease in
      patients with HIV/AIDS. DESIGN: Retrospective analysis of clinic database.
      SETTING: An open-access dental clinic dedicated to the dental treatment of
      patients infected with HIV in London, UK. SUBJECTS: Dental patients attending for
      routine assessment (check-up). MAIN OUTCOME MEASURES: Prevalence of HIV
      associated oral lesions, diagnosed in accordance with EC classification criteria,
      in patients taking and not taking antiretroviral therapies (ARTs). RESULTS: Data
      were collected at 2789 dental examinations for 1590 patients between 1992 and
      1998. More patients taking ART had one or more oral manifestations in the years
      up to 1996, after which the prevalence fell to a similar level to those not
      taking medications. The prevalence of mucosal disease in patients not taking ART
      was relatively constant over time. These trends were observed for oral hairy
      leukoplakia, pseudomembranous and erythematous candidiasis and Kaposi's sarcoma
      but not for oral papillomata. CONCLUSIONS: These data provide evidence that
      decreases in the prevalence of oral disease in people with HIV infection can be
      attributed to the effectiveness of ART.

PMID- 11991310
TI  - Prevalence of hepatitis virus infection in association with oral diseases
      requiring surgery.
AB  - OBJECTIVE: We evaluated the prevalence of hepatitis virus infection in a large
      population of patients in terms of diseases requiring oral surgery. DESIGN:
      Retrospective case survey. SUBJECTS AND METHODS: Prevalence of hepatitis B and C
      virus (HBV, HCV) infection were compared between oral diseases such as
      inflammation, cysts, cancer, trauma, benign tumors, impacted teeth, or jaw
      deformity in dental inpatients (n = 5830) with adjustment for age, gender, and
      history of surgery. RESULTS: Of 4402 inpatients, 94 had HB surface(s) antigen
      (2.1%), while 151 of 2613 were seropositive for HCV (5.8%). Prevalences of HBs
      antigen and HCV antibody exceeded those in the general population. HBs antigen
      was more prevalent in patients with benign oral tumors than in patients with
      impacted teeth, whether or not adjustment was made for age (odds ratios, 4.246
      and 5.055 with and without age adjustment, respectively; P < 0.05). On the other
      hand, HCV antibody was more prevalent in patients with oral cancer than in those
      with impacted teeth before adjustment for age (odds ratios, 2.433; P < 0.05), but
      this difference was reversed with age adjustment (odds ratios, 0.443; P < 0.05).
      CONCLUSION: HBs antigen was more prevalent in patients with benign oral tumors,
      while HCV antibody was higher in patients with oral cancer. However, this
      increased incidence of HCV antibody apparently was a reflection of age. HCV
      infection may not have an etiologically important association with oral cancer.

PMID- 11991311
TI  - Preventing the transfer of Streptococcus mutans from primary molars to permanent
      first molars using chlorhexidine.
AB  - PURPOSE: The purpose of this study was to determine if the application of 1%
      chlorhexidine-containing wax on primary molars during the period of eruption of
      the first permanent molars could prevent the transfer of certain oral flora,
      namely Streptococcus mutans, to the permanent molars. METHODS: Fourteen children
      with a mean age of 6.5 years (7 males and 7 females) were assigned into two
      groups: a chlorhexidine group (n=9) in which 1% chlorhexidine-containing wax was
      painted on primary molars on one side of the mouth; and a placebo wax group (n=5)
      in which a similar wax, but without chlorhexidine, was painted on primary molars
      on the other side of the mouth. Baseline saliva samples and pooled plaque samples
      from the primary molars on both sides of the dentition were obtained from the two
      treatment groups. Following treatment, plaque samples from the occlusal fissures
      of the first permanent molars on both sides of the dentition were obtained. The
      levels of S.mutans and other members of the oral flora on the treated sides
      (chlorhexidine or placebo) were compared with those on the untreated sides.
      RESULTS: The results showed that the proportions of S.mutans to S.sanguinis were
      significantly lower in the chlorhexidine-treated sides compared to the untreated
      (P=0.04) and in the chlorhexidine-treated patients compared to placebo (P=0.029).
      CONCLUSIONS: Since lower mutans to sanguinis ratios have been associated with
      lower caries experience, treating primary molars with 1% chlorhexidine wax during
      eruption of permanent first molars may be a simple means for shifting the fissure
      flora of the permanent molars towards a more favorable balance.

PMID- 11991312
TI  - Changes in incremental weight and well-being of children with rampant caries
      following complete dental rehabilitation.
AB  - PURPOSE: The purposes of this study were to determine if young children with
      rampant dental caries that received complete dental rehabilitation under general
      anesthesia: 1.) weighed less preoperatively compared to national norms; and 2.)
      demonstrated significant improvement postoperatively in percentile weight gain
      and/or quality of life indicators. METHODS: The preoperative and postoperative
      percentile weights based on national norms were calculated for children, aged 2-7
      years old, with non-significant medical histories (absence of systemic illness)
      that underwent rehabilitation for rampant dental caries under general anesthesia.
      Changes in the quality of the children's life following dental rehabilitation
      under general anesthesia were determined from parental report. RESULTS: The
      results showed that there was a slight, non-significant increase in the mean
      percentile weight following dental rehabilitation under general anesthesia. There
      was no significant effect on the mean net percentile weight change based on the
      chronological age or weighing interval. There was, however, a significant
      improvement in the children's quality of life as reported by their parents.
      CONCLUSIONS: Contrary to previous reports, the mean percentile weight of children
      with rampant dental caries was not below the 50th percentile and the slight gain
      in percentile weight following dental rehabilitation under general anesthesia was
      not indicative of a "catch-up growth" phenomenon. There was, however, a
      significant improvement in the children's quality of life as based upon parental
      report and confirmed in a previous investigations.

PMID- 11991313
TI  - The effect of music distraction on pain, anxiety and behavior in pediatric dental
      patients.
AB  - PURPOSE: The purpose of this study was to determine if audio distraction could
      decrease patient anxiety, pain and disruptive behavior during pediatric dental
      procedures. METHODS: Forty-five children between the ages of 4 to 6 years had two
      visits each involving restorative dentistry with local anesthesia in a mandibular
      quadrant. Visit #1 was a baseline session for all patients. During visit #2, the
      children were assigned to either an upbeat music group, a relaxing music group or
      a no music group. Variables measured were: (1) parent-reported anxiety via the
      Modified Corah Anxiety Scale, (2) self-reported anxiety via the Venham picture
      scale, (3) heart rate, (4) behavior via the North Carolina Behavior Rating Scale
      and (5) pain via a visual analogue scale. RESULTS: No significant differences
      were found among the three groups during experimental visit #2 across any
      variables. A majority of patients (90%) stated that they enjoyed the music and
      would like to listen to it during their next visit. CONCLUSIONS: Audio
      distraction was not an effective means of reducing anxiety, pain or uncooperative
      behavior during pediatric restorative dental procedures. However, patients did
      enjoy listening to the music during their visits.

PMID- 11991314
TI  - Lack of cooperation in pediatric dentistry--the role of child personality
      characteristics.
AB  - PURPOSE: This study aimed to investigate fear, temperament, behavioral symptoms
      and verbal intelligence in a study group of uncooperative child dental patients,
      partly in comparison with a reference group of ordinary child dental patients. A
      second aim was to explore a hypothesis of heterogeneity by searching for
      subgroups within the study group. METHODS: Parents of 86 study group children (36
      aged 4-to 7- years and 50 aged 8- to 12-years) and 117 reference group children
      (8- to 12-years) answered a questionnaire concerning dental and general fear,
      temperament and general behavior. Study group children performed a vocabulary
      test to measure verbal intelligence. Data were analyzed with a variable-based and
      a person-based approach. RESULTS: In addition to dental fear, a higher level of
      impulsivity most clearly discriminated study group from reference group children.
      Cluster analyses revealed four different fear and personality subgroups within
      the study group. CONCLUSIONS: Uncooperative child dental patients constitute a
      heterogeneous group. Subgroups with different fear, temperament and behavior
      problem profiles can be identified. These subgroups could be presumed to benefit
      from different treatment regimens, which should be further investigated.

PMID- 11991315
TI  - Oral midazolam with and without meperidine for management of the difficult young
      pediatric dental patient: a retrospective study.
AB  - PURPOSE: The purpose of this retrospective study was to examine different dosages
      of midazolam used alone or in combination with different dosages of meperidine
      for managing difficult young pediatric dental patients. METHODS: Patient records
      and sedation logs of 120 moderately to severely apprehensive/ uncooperative
      subjects, ages 24-48 mos, sedated in private practice setting, were reviewed.
      Subjects, divided into six groups of 20, received midazolam in doses of 0.7 or
      1.0 mg/kg with and without meperidine in doses of 1.0 or 1.5 mg/kg. Ratings of
      the effectiveness of sedation, duration of action, need for restraint to
      accomplish treatment, and recovery times were made. Nitrous oxide was not used.
      RESULTS: When used alone, use of 0.7 mg/kg midazolam produced the most agitation,
      required restraint most frequently, and produced the shortest working time
      (P<0.001). Subjects receiving 1.0 mg/kg midazolam and meperidine were the most
      effective, completing 20/20 visits with no need for restraint, no loss of
      consciousness throughout appointments, and no adverse reactions (P<0.001). Use of
      lower dose midazolam and higher dose meperidine was reliable, permitting
      treatment to be completed without restraint in 18/20 patients. Combined higher
      doses of both agents demonstrated somnolence and oversedation. The addition of
      meperidine increased working time (P<0.05). CONCLUSIONS: The addition of
      meperidine appears to enhance the effectiveness and duration of action of
      midazolam for managing difficult young pediatric patients.

PMID- 11991316
TI  - Internet usage by pediatric dental practices in Connecticut.
AB  - PURPOSE: The aim of this study was to determine Internet usage by pediatric
      dental practices in Connecticut. METHODS: A seven-item anonymous survey was
      mailed to all the 64 pediatric dentists in private practice in Connecticut. Each
      survey form was mailed along with a stamped and pre-addressed return envelope.
      Frequency distribution analyses and chi-square tests were performed. RESULTS: The
      survey had a response rate of 73%. More than three-fourths of the pediatric
      dental practices were connected to the Internet. Seventy-two percent of the
      practices submitted third-party claims electronically. Almost all of the
      respondents did not use email to communicate with patients or to discuss
      individual patient issues with other health care providers. Only two-fifths of
      the practices had a World Wide Web site. CONCLUSIONS: Most of the pediatric
      dental practices in Connecticut were connected to the Internet. Electronic third
      party claims submission was the predominant Internet service used by these
      practices.

PMID- 11991317
TI  - Bonded resin composite strip crowns for primary incisors: clinical tips for a
      successful outcome.
AB  - The bonded resin composite strip crown is perhaps the most esthetic of all the
      restorations available to the clinician for the treatment of severely decayed
      primary incisors. However, strip crowns are also the most technique-sensitive and
      may be difficult to place. The purpose of this step-by-step technique article is
      to present some simple clinical tips to assist the clinician in achieving an
      esthetic and superior outcome.

PMID- 11991318
TI  - Multiple congenitally missing primary teeth: report of a case.
AB  - The prevalence, possible etiological factors and management of multiple missing
      primary teeth was briefly reviewed. Oligodontia of the primary dentition is a
      rare finding. This paper reports a rare case of multiple missing (n=9) primary
      teeth in a 3-year-old male of Asian origin.

PMID- 11991319
TI  - The implications of a broken needle in the pterygomandibular space: clinical
      guidelines for prevention and retrieval.
AB  - The implication of a broken anesthetic injection needle in the posterior part of
      the oral cavity is described. Needle breakage is preventable if proper preventive
      measures are used during local anesthesia administration. A broken needle should
      be removed immediately after a thorough localization and not left in the tissue,
      as previously believed. Computerized tomography (CT) scan is the proper
      diagnostic device to locate a broken needle. A careful surgical approach under
      general anesthesia is recommended to retrieve the needle. Clinical preventive
      guidelines are described and presented to the pediatric dentist.

PMID- 11991320
TI  - Concentration of formocresol used by pediatric dentists in primary tooth
      pulpotomy.
AB  - Diluted formocresol is the most widely recommended primary tooth pulpotomy
      medicament, but it is not commercially available. This investigation surveyed
      practicing pediatric dentists about the concentration of formocresol that they
      use to perform pulpotomies and, if they use diluted formocresol, where they
      obtain it. Eight-hundred-and-six surveys were sent to a randomly selected sample
      of practicing pediatric dentists, and 422 were returned for a 52% response rate.
      Eighty-four percent of the respondents use formocresol for their primary tooth
      pulpotomies. Of those, 69% use full strength, 27% use diluted and 4% don't know.
      Sources of diluted formocresol for those who use the diluted form include: 34%
      who buy it that way, 58% who dilute it themselves and 8% who have the pharmacy
      dilute it. The majority of pediatric dentists who use formocresol for primary
      tooth pulpotomies use a full strength formulation.

PMID- 11991321
TI  - Board certification: what are the options?

PMID- 11991322
TI  - Real change is difficult.

PMID- 11991323
TI  - Use of the sippy cup.

PMID- 11991324
TI  - Year one visit.

PMID- 11991325
TI  - Outcomes for root-fractured permanent incisors: a retrospective study.
AB  - PURPOSE: The objective of this study was to assess the outcomes for treated root
      fractured permanent incisors with respect to pulp vitality, root tissue union,
      and tooth survival and to examine the effects of clinical and radiographic
      parameters and rigid splinting on the outcome. METHODS: Eighty-four teeth were
      identified and data extracted from case notes prior to transfer to an SPSS data
      base for analysis. The odds ratios for each factor were calculated and the
      significance of differences was determined. Tooth loss and relevant risk
      variables were examined using Cox's regression model and Kaplan-Meyer survival
      curves. RESULTS: Fourteen (17%) had fractures in the apical third, 47 (56%) in
      the middle third, and 23 (27%) in the coronal (gingival) third. Twenty-four (29%)
      also had crown fractures involving enamel and dentine. Crown fractures were
      identified as significant risk factors for pulp vitality. Loss of pulp vitality,
      horizontal displacement, and extrusive displacement of the coronal fragment were
      significant risk factors for hard root tissue union. Survival was poorest with
      gingival third fractures with 14 (61%) of these teeth being lost. Splinting
      rigidly had no significant effect on pulp vitality and type of root tissue
      healing. CONCLUSIONS: Loss of pulp vitality was significantly associated with
      enamel-dentine crown fracture. Hard root tissue union was significantly affected
      by pulp necrosis and luxation of the coronal fragment. Survival was poorest for
      root fractures within the gingival third of the root. Splinting with rigid
      fixation had no significant effect on pulp vitality and type of root tissue
      union.

PMID- 11991326
TI  - In situ fluorescent nick translation procedure for plant chromosomes.
AB  - Pectinase and cellulase, which are used to macerate plant material, always show
      traces of DNase activities that result in DNA nicking. Moreover, the DNA
      polymerase I usually applied in the in situ nick translation techniques shows
      both 5' to 3' and 3' to 5' exonuclease activities. As a result, significant
      nonspecific labeling appears in control preparations that are not digested by a
      restriction endonuclease. Our procedure includes blocking nonspecific nick
      labeling before incubation with restriction enzymes (HpaII and HaeIII). This is
      achieved by incorporation of ddGTP into DNA by the Taq polymerase which lacks 3'
      to 5' exonuclease activity. This method gives satisfactory results because it
      eliminates nonspecific nick translation signals that are present after applying
      the methods described for animal material.

PMID- 11991327
TI  - Branching patterns of rabbit oculomotor and trochlear nerves demonstrated by
      Sihler's stain technique.
AB  - A modified Sihler's stain technique was used to visualize the branching patterns
      of oculomotor and trochlear nerves. The levator palpebrae, superior rectus,
      inferior rectus, medial rectus, inferior oblique, superior oblique and tensor
      trochlea muscles were isolated from the eyes of normal rabbits and processed
      using modified Sihler's technique. The distributions and terminal ramifications
      of the oculomotor and trochlear nerves were observed. Two distinct divisions and
      terminal branches of the oculomotor nerve were shown in detail together with the
      trochlear nerve distribution. The application of Sihler's technique enables
      researchers to trace nerve branching within relatively transparent muscles,
      whereas the nerve fibers are counterstained and clearly visible. This technique
      could be useful for detailed studies of the motor control of extraocular muscles.

PMID- 11991328
TI  - Proliferative activity in the cerebellar external granular layer evaluated by
      bromodeoxyuridine labeling.
AB  - We have optimised an indirect immunoperoxidase technique demonstrating
      bromodeoxyuridine (BrdU) incorporation into dividing cells for cerebellar tissue
      sections of four-day-old rats injected with this marker. This permits confident
      identification of granule-cell precursors engaged in DNA synthesis in the
      external granular layer of the developing cerebellum. Preservation of BrdU
      immunoreactivity is attained using methanol/acetic acid fixation and different
      pretreatments before immunostaining, while unlabeled nuclei can be recognized
      clearly after Feulgen or hematoxylin counterstaining. We established conditions
      to ensure satisfactory BrdU uptake without affecting cell-cycle progression
      during the postlabeling time period. The dose of BrdU employed provides
      saturation S-phase labeling from at least 1 h after BrdU delivery. Various
      kinetic parameters and phase durations have been determined in experiments
      involving a single injection or cumulative labeling sequences, and the cycle time
      was calculated based on two models of generative behavior: steady-state and
      exponential growth. The working hypothesis of steady-state kinetics can be
      adopted successfully if the existence of neuroblasts with different proliferation
      rates is taken into account.

PMID- 11991329
TI  - Biological staining: mechanisms and theory.
AB  - New staining techniques continue to be introduced, and older ones continue to be
      used and improved. Several factors control specificity, selectivity and
      visibility of the end product in any procedure using dyes, fluorochromes,
      inorganic reagents or histochemical reactions applied to sections or similar
      preparations. Local concentration of the tissue target often determines the
      intensity of the observed color, as does the fine structure within the object
      being stained, which may facilitate or impede diffusion of dyes and other
      reagents. Several contributions to affinity control the specificity of staining.
      These include electrical forces, which result in accumulation of dye ions in
      regions of oppositely charged tissue polyions. Weaker short-range attractions
      (hydrogen bonding, van der Waals forces or hydrophobic bonding, depending on the
      solvent) hold dyes ions and histochemical end products in contact with their
      macromolecular substrates. Nonionic forces can also increase visibility of
      stained sites by causing aggregation of dye molecules. Covalent bonds between dye
      and tissue result in the strongest binding, such as in methods using Schiff's
      reagent and possibly also some mordant dyes. The rate at which a reagent gains
      access to or is removed from targets in a section or other specimen affect what
      is stained, especially when more then one dye is used, together or sequentially.
      Rate-controlled staining is greatly influenced by the presence and type of
      embedding medium, such as a resin, that infiltrates the tissue. The rates of
      chemical reactions are major determinants of outcome in many histochemical
      techniques. Selective staining of different organelles within living cells is
      accomplished mainly with fluorochromes and is controlled by mechanisms different
      from those that apply to fixed tissues. Quantitative structure-activity relations
      (QSAR) of such reagents can be derived from such molecular properties as
      hydrophilic-hydrophobic balance, extent of conjugated bond systems, acid-base
      properties and ionic charge. The QSAR correlates with staining of endoplasmic
      reticulum, lysosomes, mitochondria, DNA, or the plasma membranes of living cells.

PMID- 11991330
TI  - A new technique for hard tissues.
AB  - Fossil tissues generally require specialized processing. Most thin sectioning
      techniques yield unstained sections or require unwieldy methods to produce
      stained sections. I outline here two simple techniques for producing stained,
      ground, thin sections using readily available Romanowsky-type cytology stains and
      a urine sediment stain. Results are comparable to hematoxylin and eosin stained
      specimens.

PMID- 11991331
TI  - "To do no harm" survey of NMA physicians regarding perceptions on DTC
      advertisements. National Medical Association.

PMID- 11991332
TI  - Position statement of the National Medical Association on Direct to Consumer
      advertising.

PMID- 11991333
TI  - Acquired immunodeficiency syndrome in older African Americans.
AB  - The purpose of this study was to determine if older African Americans are
      disproportionately affected by acquired immunodeficiency syndrome (AIDS), and to
      review the clinical impact of AIDS and the importance of prevention and treatment
      efforts. A review of the literature and statistics was obtained using Medline and
      the AIDS Public Information Data Set offered by the Centers for Disease Control
      and Prevention. Twenty-seven percent of the U.S. population is above the age of
      50, and the number of AIDS cases in this group is growing, with African Americans
      accounting for the highest proportion of cases and deaths. Testing for HIV may be
      delayed and symptoms attributed to other illnesses. Though 5% of new cases occur
      in those over 50, prevention programs, testing, and the perception of risk by
      providers may be insufficient. There are few research studies on HIV treatment in
      older patients and no specific guidelines for antiretroviral treatments
      available. Although death rates for AIDS has been declining, adults over 50 still
      have the highest mortality rate. Co-morbid conditions, such as heart disease and
      hypertension, may require taking multiple drugs, which may complicate treatment.
      Increasing heterosexual transmission rates and a lack of information on HIV
      reinforces the need for specific prevention programs targeted toward older
      African Americans.

PMID- 11991334
TI  - Racial and ethnic disparities in childhood asthma diagnosis: the role of clinical
      findings.
AB  - OBJECTIVES: To establish rates of childhood asthma symptoms, diagnosis, and
      hospitalization by race, ethnicity, and income, and to ascertain if elevated
      reported prevalence of asthma diagnosis among African-American children could be
      explained by differences in clinical findings. METHODS: Estimates of each
      indicator were calculated based on data from the third National Health and
      Nutrition and Examination Survey (NHANES III). Bivariate and multivariate
      logistic regression models were estimated to predict parent or guardian report of
      current asthma diagnosis. RESULTS: African-American children aged 1 to 5 have a 2
      fold higher probability of both asthma diagnosis and hospitalization during the
      previous year but no significant difference in wheeze prevalence compared to
      Mexican-American and European-American children. These differences are not
      explained by household income or clinical information. Children aged 6 to 16 had
      similar rates of diagnosis and hospitalization for all racial/ethnic groups,
      although African-American children reported wheeze symptoms one-third less often.
      CONCLUSIONS: Although younger African-American children have higher morbidity
      from asthma than their Mexican-American and European-American peers, clinical
      findings were similar and did not explain increased rates of diagnosis.
      Interpersonal dynamics within families and communication between families and
      clinicians are believed to influence both symptom reporting and diagnosis
      generation.

PMID- 11991335
TI  - Developing weight loss interventions for African-American women: elements of
      successful models.
AB  - This review examines published reports of weight-loss interventions targeted to
      overweight African-American women and identifies specific factors that may
      account for the variability in observed outcomes. The review will identify
      program elements that have been associated with weight loss in obese African
      American women, describe behavior modification elements of weight loss programs,
      and provide a list of "lessons learned" that may be useful in planning future
      weight-loss intervention programs for this target population.

PMID- 11991336
TI  - A model of psychosocial and cultural antecedents of blood pressure control.
AB  - Hypertension is a major modifiable risk factor for stroke, congestive heart
      failure, and end-stage renal disease. Hypertension is particularly prevalent and
      deadly among African Americans. Effective treatment for hypertension has been
      available for decades, yet only one fourth of all individuals have their blood
      pressure under control. Despite the potential impact of hypertension,
      interventions to improve control have had limited success. We present a model of
      how to understand antecedents of blood pressure control according to three
      interrelated categories: patient characteristics, social and cultural
      environment, and medical environment. This theoretical paper was conducted using
      a literature review and a model to explain psychosocial antecedents of blood
      pressure control is presented. We conclude that improved understanding of
      important antecedents of blood pressure control coupled with technological
      advances, such as tailored interventions, provide clinicians with a tool that may
      lead to improved blood pressure control. These interventions will require the
      involvement of clinicians and consideration of sociocultural factors to be
      successful.

PMID- 11991337
TI  - Impact of a Drug Abuse Resistance Education (D.A.R.E) program in preventing the
      initiation of cigarette smoking in fifth- and sixth-grade students.
AB  - An alarmingly high number of children become addicted to tobacco use. To teach
      children the skills to resist the influences surrounding the initiation of
      tobacco and other drug use, a Drug Abuse Resistance Education (D.A.R.E.) program
      is being implemented in three fourths of the schools in the United States. The
      purpose of this study is to examine the impact of this program in preventing
      smoking. A survey was conducted among 236 fifth and sixth graders in Nashville,
      Tennessee. Of the students included in the survey, 88% graduated from D.A.R.E.
      Approximately 11.6% of respondents had ever smoked cigarettes; 86% of them
      continued to smoke. The D.A.R.E. group had a significantly lower rate of smoking
      compared with their non-D.A.R.E. counterparts (8.7% vs. 28.0%; p = 0.0001).
      Logistic regression analysis shows that the D.A.R.E. group was five times (odds
      4.9; p = 0.003; 95% CI: 1.7, 14.0) less likely to initiate smoking compared with
      the non-D.A.R.E. group. The D.A.R.E. group had a significantly (p = 0.002) higher
      knowledge score on the risk of smoking. The knowledge score has strong opposite
      correlation to smoking behavior (p = 0.00001). Students with top-quartile
      knowledge scores had a substantially lower rates of smoking (1.4% vs. 14.4%; p =
      0.001). This finding is consistent for both African-American (0% vs. 19.6%; p =
      0.001) and white children (1.9% vs. 13%; p = 0.001). The D.A.R.E. program may
      have an impact in preventing the initiation of smoking behavior.

PMID- 11991338
TI  - Knowledge, attitudes, and behavior of homeless African-American adolescents:
      implications for HIV/AIDS prevention.
AB  - The purpose of this pilot study was to describe the knowledge of HIV/AIDS,
      attitudes about condom use, and the sexual behavior of African-American
      adolescents who reside in a children's emergency homeless shelter. The Attitudes
      Toward Condom Usage Questionnaire, the AIDS Knowledge and Attitude Survey, and a
      Perceived Risk of HIV/AIDS Scale were modified and administered to 37 African
      American male and female adolescents who reside in an emergency shelter. HIV/AIDS
      knowledge and attitudes about condoms among these respondents were comparable to
      those of other adolescents described in the literature in that there was a strong
      knowledge of HIV/AIDS, although sexual behavior and attitudes toward condoms were
      not consistent with this knowledge. Significant differences between male and
      female respondents were only found on three items of the Attitudes Toward Condom
      Usage Questionnaire and on the Perceived Risk of HIV/AIDS Scale at the 0.05
      level. The knowledge, attitudes, and sexual behavior of homeless, African
      American adolescents should be examined to develop and implement appropriate
      programs to address the specific needs of this population. Further research
      should focus on this population and expand on this preliminary data.

PMID- 11991339
TI  - Atrial fibrillation: an important issue for African Americans?

PMID- 11991340
TI  - African Americans in medicine.

PMID- 11991341
TI  - Clinical trial minority recruitment: still an unmet need.

PMID- 11991342
TI  - After-hours telephone calls.

PMID- 11991343
TI  - Clinical effects of grapefruit juice-nifedipine interaction in a 54-year-old
      Nigerian: a case report.
AB  - Grapefruit juice is known to increase the oral bioavailability of dihydropyridine
      calcium channel blockers, including nifedipine, by reducing presystemic
      clearance. The nature and magnitude of this interaction has not been studied in
      black Africans. Previous studies have reported reduced systemic clearance of
      nifedipine in this population, suggesting altered risk from the interaction of
      grapefruit juice and nifedipine. We report a case of a nifedipine-grapefruit
      juice adverse interaction in a Nigerian to draw attention to the problem and
      further sensitize practitioners.

PMID- 11991344
TI  - Neuroleptic malignant syndrome presenting as pulmonary edema and severe
      bronchorrhea.
AB  - Neuroleptic malignant syndrome is a rare (incidence, 0.02%-3.2%) but dangerous
      complication following the use of neuroleptic drugs. When not promptly
      recognized, this disease carries a high mortality (10%-20%) and morbidity rate.
      We report an unusual case of neuroleptic malignant syndrome that presented
      predominantly with autonomic instability in the form of recurrent episodes of
      respiratory distress. The respiratory distress was initially caused by pulmonary
      edema and later was caused by severe bronchorrhea. We propose that aspiration
      pneumonia resulting in respiratory failure, the leading cause of death in
      neuroleptic malignant syndrome, may be a result of a combination of altered
      mental status and bronchorrhea. This has therapeutic implications because early
      institution of bromocriptine/dantrolene can prevent aspiration pneumonia and,
      hence, mortality from respiratory failure.

PMID- 11991345
TI  - Yogurt: still a favorite for vaginal candidiasis?

PMID- 11991346
TI  - Importance of hand-washing.

PMID- 11991347
TI  - Obesity rates skyrocketing.

PMID- 11991348
TI  - Doctors say all newborns need Hepatitis B shot.

PMID- 11991349
TI  - States cut Medicaid benefits amid recession, revenue declines.

PMID- 11991350
TI  - Gene therapy may lead to cure for sickle cell patients.

PMID- 11991351
TI  - NMRKIN: simulating line shapes from two-dimensional spectra of proteins upon
      ligand binding.
AB  - The analysis of the shape of signals in NMR spectra is a powerful tool to study
      exchange and reaction kinetics. Line shapes in two-dimensional spectra of
      proteins recorded for titrations with ligands provide information about binding
      rates observed at individual residues. Here we describe a fast method to simulate
      a series of line shapes derived from two-dimensional spectra of a protein during
      a ligand titration. This procedure, which takes the mutual effects of two
      dimensions into account, has been implemented in MATLAB as an add-on to NMRLab
      (Gunther et al., 2000). In addition, more complex kinetic models, including
      sequential and parallel reactions, were simulated to demonstrate common features
      of more complex line shapes which could be encountered in protein-ligand
      interactions. As an example of this method, we describe its application to line
      shapes obtained for a titration of the p85 N-SH2 domain of PI3-kinase with a
      peptide derived from polyomavirus middle T antigen (MT).

PMID- 11991352
TI  - Solution structure and dynamics of melanoma inhibitory activity protein.
AB  - Melanoma inhibitory activity (MIA) is a small secreted protein that is implicated
      in cartilage cell maintenance and melanoma metastasis. It is representative of a
      recently discovered family of proteins that contain a Src Homologous 3 (SH3)
      subdomain. While SH3 domains are normally found in intracellular proteins and
      mediate protein-protein interactions via recognition of polyproline helices, MIA
      is single-domain extracellular protein, and it probably binds to a different
      class of ligands. Here we report the assignments, solution structure, and
      dynamics of human MIA determined by heteronuclear NMR methods. The structures
      were calculated in a semi-automated manner without manual assignment of NOE
      crosspeaks, and have a backbone rmsd of 0.38 A over the ordered regions of the
      protein. The structure consists of an SH3-like subdomain with N- and C-terminal
      extensions of approximately 20 amino acids each that together form a novel fold.
      The rmsd between the solution structure and our recently reported crystal
      structure is 0.86 A over the ordered regions of the backbone, and the main
      differences are localized to the most dynamic regions of the protein. The
      similarity between the NMR and crystal structures supports the use of automated
      NOE assignments and ambiguous restraints to accelerate the calculation of NMR
      structures.

PMID- 11991353
TI  - Towards high-resolution solid-state NMR on large uniformly 15N- and [13C,15N]
      labeled membrane proteins in oriented lipid bilayers.
AB  - Based on exact numerical simulations, taking into account isotropic and
      conformation-dependent anisotropic nuclear spin interactions, we systematically
      analyse the prospects for high-resolution solid-state NMR on large isotope
      labeled membrane proteins macroscopically oriented in phospholipid bilayers.
      Using the known X-ray structures of rhodopsin and porin as models for large
      membrane proteins with typical alpha-helical and beta-barrel structural motifs,
      the analysis considers all possible one- to six-dimensional spectra comprised of
      frequency dimensions with evolution under any combination of amide 1H, amide 15N,
      and carbonyl 13C chemical shifts as well as 1H-15N dipole-dipole couplings. Under
      consideration of typical nuclear spin interaction and experimental line-shape
      parameters, the analysis provides new insight into the resolution capability and
      orientation-dependent transfer efficiency of existing experiments as well as
      guidelines as to improved experimental approaches for the study of large
      uniformly 15N- and [13C,15N]-labeled membrane proteins. On basis of these results
      and numerical optimizations of coherence-transfer efficiencies, we propose
      several new high-resolution experiments for sequential protein backbone
      assignment and structure determination.

PMID- 11991354
TI  - Automated assignment and 3D structure calculations using combinations of 2D
      homonuclear and 3D heteronuclear NOESY spectra.
AB  - The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance
      geometry to generate 3D structures from unassigned NOESY spectra. In this study
      we determined the minimum set of experiments needed to generate a high quality
      structure bundle. Different combinations of 3D 15N-edited, 13C-edited HSQC-NOESY
      and 2D homonuclear 1H-1H NOESY spectra of the 77 amino acid protein, myeloid
      progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD
      calculations. The quality of the assignments of NOESY cross peaks and the
      accuracy of the automatically generated 3D structures were compared to those
      obtained with a conventional manual procedure. Combining data from two types of
      experiments synergistically increased the number of peaks assigned unambiguously
      in both individual spectra. As a general trend for the accuracy of the structures
      we observed structural variations in the backbone fold of the final structures of
      about 2 A for single spectral data, of 1 A to 1.5 A for double spectral data, and
      of 0.6 A for triple spectral data sets. The quality of the assignments and 3D
      structures from the optimal data using all three spectra were similar to those
      obtained from traditional assignment methods with structural variations within
      the bundle of 0.6 A and 1.3 A for backbone and heavy atoms, respectively. Almost
      all constraints (97%) of the automatic NOESY cross peak assignments were cross
      compatible with the structures from the conventional manual assignment procedure,
      and an even larger proportion (99%) of the manually derived constraints were
      compatible with the automatically determined 3D structures. The two mean
      structures determined by both methods differed only by 1.3 A rmsd for the
      backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD
      analysis of spectra from labeled proteins provides a reliable method for high
      throughput analysis of genomic targets.

PMID- 11991355
TI  - High-resolution NMR structure of an AT-rich DNA sequence.
AB  - We have determined, by proton NMR and complete relaxation matrix methods, the
      high-resolution structure of a DNA oligonucleotide in solution with nine
      contiguous AT base pairs. The stretch of AT pairs, TAATTATAA x TTATAATTA, is
      imbedded in a 27-nucleotide stem-and-loop construct, which is stabilized by
      terminal GC base pairs and an extraordinarily stable DNA loop GAA (Hirao et al.,
      1994, Nucleic Acids Res. 22, 576-582). The AT-rich sequence has three repeated
      TAA x TTA motifs, one in the reverse orientation. Comparison of the local
      conformations of the three motifs shows that the sequence context has a minor
      effect here: atomic RMSD between the three TAA x TTA fragments is 0.4-0.5 A,
      while each fragment is defined within the RMSD of 0.3-0.4 A. The AT-rich stem
      also contains a consensus sequence for the Pribnow box, TATAAT. The TpA, ApT, and
      TpT x ApA steps have characteristic local conformations, a combination of which
      determines a unique sequence-dependent pattern of minor groove width variation.
      All three TpA steps are locally bent in the direction compressing the major
      groove of DNA. These bends, however, compensate each other, because of their
      relative position in the sequence, so that the overall helical axis is
      essentially straight.

PMID- 11991356
TI  - Improving the quality of protein structures derived by NMR spectroscopy.
AB  - Biomolecular structures provide the basis for many studies in several research
      areas such as homology modelling, structure-based drug design and functional
      genomics. It is an important prerequisite that the structure is reliable in terms
      of accurate description of the experimental data, and in terms of good quality of
      local- and overall geometry. Recent surveys indicate that structures solved by
      NMR-spectroscopy normally are of lower precision than high-resolution X-ray
      structures. Here, we present a refinement protocol that improves the quality of
      protein structures determined by NMR-spectroscopy to the level of those
      determined by high resolution X-ray crystallography in terms of local geometry.
      The protocol was tested on experimental data of the proteins IL4 and Ubiquitin
      and on simulated data of the protein Crambin. In almost all aspects, the protocol
      yielded better results in terms of accuracy and precision. Independent validation
      of the results for Ubiquitin, using residual dipolar couplings, indicates that
      the ensemble of NMR structure is substantially improved by the protocol.

PMID- 11991357
TI  - Solution structure of the hypothetical protein MTH0637 from Methanobacterium
      thermoautotrophicum.

PMID- 11991358
TI  - 1H(N), 15N, 13CO, 13Calpha, 13Cbeta assignment and secondary structure of a 20
      kDa alpha-L-fucosidase from pea using TROSY.

PMID- 11991359
TI  - Semi-automated backbone resonance assignments of the extracellular ligand-binding
      domain of an ionotropic glutamate receptor.

PMID- 11991360
TI  - 1H, 13C, and 15N resonance assignments and secondary structure of the PWI domain
      from SRm160 using reduced dimensionality NMR.

PMID- 11991361
TI  - Base excision repair: NMR backbone assignments of Escherichia coli
      formamidopyrimidine-DNA glycosylase.

PMID- 11991362
TI  - Centennial of Einthoven's first recording of the human electrocardiogram with the
      string galvanometer.

PMID- 11991363
TI  - Phased-array intracardiac echocardiography for guiding transseptal catheter
      placement: utility and learning curve.
AB  - The utility of a new intracardiac 64-element, phased-array, longitudinal
      ultrasound imaging system for guiding transseptal catheterization was assessed
      during 69 crossing attempts in 45 dogs because of the inherent limitations of
      fluoroscopy and mechanical ultrasound. Multifrequency (7.5-8.5 MHZ) imaging of
      the membranous fossa ovalis, posterior left atrium, and left atrial appendage was
      conducted from the right atrium. Contact of the Brockenbrough needle with the
      interatrial septum as reflected by membranous fossa ovalis "tenting" was
      uniformly identified. Transseptal crossing and advancement of the dilator and
      sheath were adequately imaged because of deeper ultrasound tissue penetration.
      Transseptal catheterization was successfully accomplished in 44 of 45 dogs: on
      the first attempt in 40 and with additional attempts in 4 and confirmed by direct
      far-field imaging of nonagitated saline injection via the sheath. Total
      transseptal catheterization time was 3.0 +/- 1.8 minutes. Unsuccessful first
      attempts and/or subsequent sheath pullback into the right atrium with catheter
      manipulation were also readily recognized. Insertion of the transseptal needle
      beyond the ultrasound imaging plane resulted in perforation of the posterior left
      atrial wall in three attempts. Accompanying effusions in these animals and three
      others related to subsequent intracardiac ablation catheter manipulation were
      readily identified and monitored echocardiographically. In conclusion, phased
      array intracardiac imaging provides a highly reliable means of guiding
      transseptal access to the left atrium. In addition, inadvertent complications
      such as perforation and pericardial effusion development can be readily
      recognized.

PMID- 11991364
TI  - Clinical predictors of defibrillation thresholds with an active pectoral pulse
      generator lead system.
AB  - Active pectoral pulse generators are used routinely for initial ICD placement
      because they reduce DFTs and simplify the implantation procedure. Despite the
      common use of these systems, little is known regarding the clinical predictors of
      defibrillation efficacy with active pulse generator lead configurations. Such
      predictors would be helpful to identify patients likely to require higher output
      devices or more complicated implantations. This was a prospective evaluation of
      DFT using a uniform testing protocol in 102 consecutive patients with an active
      pectoral can and dual coil transvenous lead. For each patient, the DFT was
      measured with a step-down protocol. In addition, 34 parameters were assessed
      including standard clinical echocardiographic and radiographic measures.
      Multivariate stepwise regression analysis was performed to identify independent
      predictors of the DFT. The mean DFT was 9.3 +/- 4.6 J and 93% (95/102) of
      patients had a DFT < or = 15 J. The QRS duration, interventricular septum
      thickness, left ventricular mass, and mass index were significant but weak (R <
      0.3) univariate predictors of DFT. The left ventricular mass was the only
      independent predictor by multivariate analysis, but this parameter accounted for
      < 5% of the variability of DFT measured (adjusted R2 = 0.047, P = 0.017). The
      authors concluded that an acceptable DFT (< 15 J) is observed in > 90% of
      patients with this dual coil and active pectoral can lead system. Clinical
      factors are of limited use for predicting DFTs and identifying those patients who
      will have high thresholds.

PMID- 11991365
TI  - Mapping the coronary sinus and great cardiac vein.
AB  - The purpose of this study was to develop a better understanding of the pacing and
      sensing characteristics of electrodes placed in the proximal cardiac veins. A
      detailed mapping of the coronary sinus (CS) and great cardiac vein (GCV) was done
      on 25 patients with normal sinus rhythm using a deflectable electrophysiological
      catheter. Intrinsic bipolar electrograms and atrial and ventricular pacing
      voltage thresholds were measured. For measurement purposes, the GCV and the CS
      were each subdivided into distal (D), middle (M), and proximal (P) regions, for a
      total of six test locations. Within the CS and GCV, the average atrial pacing
      threshold was always lower (P < 0.05) than the ventricle with an average
      ventricular to atrial ratio > 5, except for the GCV-D. The average atrial
      threshold in the CS and GCV ranged from 0.2- to 1.0-V higher than in the atrial
      appendage. Diaphragmatic pacing was observed in three patients. Atrial signal
      amplitude was greatest in the CS-M, CS-D, and GCV-P and smaller in the CS-P, GCV
      M, and GCV-D. Electrode spacing did not significantly affect P wave amplitude,
      while narrower electrode spacing attenuated R wave amplitude. The average P:R
      ratio was highest with 5-mm-spaced electrodes compared to wider spaced pairs. The
      P:R ratio in the CS was higher (P < 0.05) than in all positions of the GVC. It is
      possible to pace the atrium independent of the ventricle at reasonably low
      thresholds and to detect atrial depolarization without undue cross-talk or noise
      using closely spaced bipolar electrode pairs. The areas of the proximal, middle,
      and distal CS produced the best combination of pacing and sensing parameters.

PMID- 11991366
TI  - Spatial resolution of body surface potential and Laplacian pace mapping.
AB  - The spatial resolution (SR) of the body surface Laplacian map (BSLM) was assessed
      using a three-dimensional, realistically shaped, heart-torso model. The BSLMs
      were estimated from the body surface potential maps (BSPMs) generated by pacing
      different sites of the ventricle of a three-dimensional computer heart model
      using a novel three-dimensional spline Laplacian algorithm. Pacing was performed
      at a total of 88 myocardial units in five regions of the AV ring (anterior, left
      wall, posterior, right wall, and septum) and three regions adjacent to the AV
      ring in the middle anterior and posterior of the ventricles. The SR of the BSPMs
      and BSLMs were investigated by means of the correlation coefficient (CC) of maps.
      When 5 microV and 10 microV Gaussian white noises were added into the simulated
      BSPMs, the SR, at 36 ms after the onset of pacing, was about 5.0 +/- 1.2 mm and
      5.4 +/- 1.3 mm for the BSPMs, and 3.3 +/- 0.8 mm and 4.0 +/- 0.9 mm for the
      BSLMs, respectively. The results of the present simulation study suggest that the
      BSLM has higher SR and may provide a more accurate means than the BSPMs for
      differentiating between the accessory pathways or the sites of other ectopic
      cardiac beats along the AV ring and in its neighboring regions.

PMID- 11991367
TI  - The effect of rate responsive pacing in patients with angina pectoris on the
      extent of ischemia on 201-thallium exercise scintigraphy.
AB  - In patients with coronary artery disease (CAD), rate responsive pacing is
      considered to be contraindicated because an increase in heart rate may increase
      oxygen demand. Although previous studies have shown no subjective increase in
      ischemia during rate responsive pacing, data from objective assessment have not
      been documented. The goal of this study was to determine if there was an increase
      in ischemia on 201-Thallium (201 Tl) exercise scintigraphy in this mode of pacing
      in patients with CAD and angina. Eighteen consecutive patients with chronic
      atrial fibrillation and symptomatic bradyarrhythmias with a pacemaker for more
      than 6 months participated in the study. In VVI and VVIR modes a symptom-limited
      exercise 201 Tl scintigram was performed in a single blind randomized crossover
      fashion. Exercise duration, anginal attacks, use of nitroglycerine (NTG) tablets,
      blood pressure, and analysis of the scintigrams were assessed during each pacing
      mode. Fifteen men and three women were included (age 65.9 +/- 4.9 years, LVEF
      0.44 +/- 0.07). Four were in Class III angina pectoris, and 14 in class II. The
      mean exercise duration increased 28% in the VVIR group without an increase in
      anginal attacks per week or the use of NTG tablets. On scintigrams, no
      differences were seen between the two groups. One patient was withdrawn from the
      study because of an increase in angina pectoris (AP) attacks during VVIR pacing.
      Rate responsive pacing is safe and effective in patients with CAD without an
      increase in subjective and objective signs of ischemia.

PMID- 11991368
TI  - QT interval in children with sensory neural hearing loss.
AB  - Long QT syndrome was first described in children with congenital sensory neural
      hearing loss (SNHL). The deafness was attributed to abnormalities in potassium
      ion channels of the inner ear. Similar channels are present in the heart and its
      dysfunction causes long QT syndrome. Whether congenital SNHL is associated with
      prolonged QT is unknown. This study examined 52 patients (median age 8.35 years,
      range 0.21-17.42 years) with SNHL and compared them to 63 healthy children
      (median age 10.2 years; range 0.67-19 years). An observer, who was blinded from
      the presence or absence of SNHL, measured QT, QTc intervals and dispersions from
      a standard 12-lead electrocardiogram. To assess the cardiac autonomic enervation,
      power spectral analysis of heart rate variability was determined using a 24-hour
      ambulatory heart rate monitor and was expressed as high (HF) to low frequency
      (LF) ratio. Left ventricular size and functions were evaluated by using two
      dimensional echocardiography. The medians (and ranges) of QT intervals were 340
      ms (230-420 ms) in patients and 320 ms (240-386 ms) in the control group (P <
      0.01). The QTc was longer in patients with SNHL (median 417 ms, range 384-490 ms)
      than in controls (median 388 ms, range 325-432 ms, P < 0.001). QT dispersions in
      SNHL were higher (median .038 ms, range 00-11 ms) than controls (median 27 ms,
      range 00-52 ms, P < 0.001). T wave inversion (n = 16) and alternans (n = 3)
      occurred in patients with SNHL. Heart rates were similar in both groups. Some
      deaf patients (n = 8) had dizzy episodes with a QTc > 440 ms. The HF:LF ratio was
      1.32 (0.516-2.33) in deaf patients and 1.428 (0.67-2.3) in the control group (P >
      0.1). Left ventricular size and functions were similar and normal in deaf
      patients and controls. In children, congenital SNHL is associated with a
      prolonged QT interval.

PMID- 11991369
TI  - Electrophysiological features of atrial tachycardia arising from the
      atrioventricular annulus.
AB  - Atrial tachycardia (AT) arises from various sites in the atrium and the
      mechanisms are nonuniform. McGuire et al. reported that the cells around the
      atrioventricular annuli resembled nodal cells in their cellular
      electrophysiology. The purpose of this study was to delineate the
      electrophysiological features of AT arising from the atrioventricular (AV)
      annulus (AVAT). The study included five patients with six AVATs that were
      abolished by the radiofrequency energy delivery. The location of the AV annuli
      was defined by using the AV ratio of the local electrograms and the amplitude of
      the ventricular electrograms, in addition to the anatomic findings under
      fluoroscopic guidance. The tachycardia cycle lengths were 403 +/- 117 ms. An AV
      ratio of the electrograms at the successful ablation sites was 0.4 +/- 0.4 at the
      tricuspid annulus and 1.5 +/- 0.3 at the mitral annulus. Small doses (mean 3.2 +/
      1.8 mg) of adenosine triphosphate could terminate all the tachycardia episodes
      for five of the ATs without the development of AV nodal conduction block. The
      successful ablation sites were located at the right mid-septum in 1 AT, right
      posteroseptum in 2 ATs, right posterolateral region in 1 AT, and left
      anteroseptum in 2 ATs. These findings suggest that the cells with nodal-type
      action potentials around both annuli might play an important role in the genesis
      of AVAT.

PMID- 11991370
TI  - Site of the arrhythmogenic focus and cardiac vulnerability to ventricular
      fibrillation.
AB  - The aim of this study was to test the hypothesis that a subendocardial
      arrhythmogenic focus makes the heart more susceptible to VF due to electrical
      interaction with the Purkinje network. Monofocal ventricular tachycardia (mVT)
      was created by injecting 5-microg aconitine into the left ventricular
      subepicardium (EPI-mVT, n = 8) or subendocardium (ENDO-mVT, n = 13) in
      anesthetized dogs. Despite the similar cycle length of mVT, the incidence of VF
      was significantly different between EPI-mVT and ENDO-mVT (100 [8/8] vs 46%
      [6/13], P <0.05). VF was invariably preceded by hemodynamic deterioration. Three
      dimensional cardiac mapping (n = 10, 221 +/- 11 recording sites) revealed that VF
      was triggered solely by focal firing unrelated to the primary arrhythmogenic
      focus in both mVT models. No interaction between the primary focus and adjacent
      endocardial tissue was indicated. These results suggest that the proximity of the
      arrhythmogenic focus to the Purkinje network has little role in cardiac
      vulnerability to VF, and that progression of mVT to VF is largely caused by
      sporadic focal firing regardless of the site of the arrhythmogenic focus in the
      present animal model.

PMID- 11991371
TI  - High accuracy of automatic detection of atrial fibrillation using wavelet
      transform of heart rate intervals.
AB  - Permanent and paroxysmal AF is a risk factor for the occurrence and the
      recurrence of stroke, which can occur as its first manifestation. However, its
      automatic identification is still unsatisfactory. In this study, a new
      mathematical approach was evaluated to automate AF identification. A derivation
      set of 30 24-hour Holter recordings, 15 with chronic AF (CAF) and 15 with sinus
      rhythm (SR), allowed the authors to establish specific RR variability
      characteristics using wavelet and fractal analysis. Then, a validation set of 50
      subjects was studied using these criteria, 19 with CAF, 16 with SR, and 15 with
      paroxysmal AF (PAF); and each QRS was classified as true or false sinus or AF
      beat. In the SR group, specificity reached 99.9%; in the CAF group, sensitivity
      reached 99.2%; in the PAF group, sensitivity reached 96.1%, and specificity
      92.6%. However, classification on a patient basis provided a sensitivity of 100%.
      This new approach showed a high sensitivity and a high specificity for automatic
      AF detection, and could be used in screening for AF in large populations at risk.

PMID- 11991372
TI  - Radiofrequency catheter ablation using cooled electrodes: impact of irrigation
      flow rate and catheter contact pressure on lesion dimensions.
AB  - Irrigation of radiofrequency current (RF) ablation reduces the risk of thrombus
      formation. The aim of this study was to investigate the impact of different
      irrigation catheter flow rates and contact pressures from the catheter on the
      development of lesion dimension and thrombus formation. A thigh muscle
      preparation was achieved in six sheep to create a cradle that was filled and
      perfused with heparinized blood (250 mL/min, 37 C degrees). RF ablation (30 s, 30
      W) was initially performed with three different irrigation flow rates (5 mL/min,
      10 mL/min, and 20 mL/min) and a perpendicular position (0.1 N contact pressure)
      of the irrigated ablation catheter ("Sprinklr," Medtronic, Inc., Minneapolis, MN,
      USA). The next lesions were induced with constant contact pressure of 0.05 Newton
      (N); 0.1 N; 0.3 and 0.5 N and a parallel or perpendicular orientation of the
      catheter, respectively. A constant irrigation flow of 10 mL/min was maintained
      during these RF applications. Cross sections of the lesions were investigated
      with regard to maximal depth and maximal diameter at and below the surface.
      During high flow irrigation (20 mL/min) the surface diameter was significantly
      smaller (0.63 +/- 0.1 cm) compared to irrigation flowrates of 5 mL/min (0.88 +/-
      0.2 cm) and 10 mL/min (1 +/- 0.1 cm). Thrombus formation was not observed during
      any RF application. Only in perpendicular catheter orientations with a contact
      pressure of 0.5 N were significantly deeper lesions (0.85 +/- 0.12 cm) induced
      compared to 0.05 N (0.55 +/- 0.02 cm), 0.1 N (0.7 +/- 0.01 cm) and 0.3 N (0.67 +/
      0.01 cm) contact pressure. There was no significant difference in lesion depth
      with different flow rates. Irrigated RF ablation even with low flow rates and
      high catheter contact pressure prevented thrombus formation at the electrode.
      Smaller lesion diameters have been created with high irrigation flow rates. The
      deeper lesion created with high catheter contact pressure might be caused by a
      greater power transmission to the tissue.

PMID- 11991373
TI  - Adenosine induced ventricular fibrillation in Wolff-Parkinson-White syndrome.
AB  - VF was observed in four patients (group A) with preexcited AF presenting to the
      emergency department who had been given 12 mg of adenosine. These patients were
      resuscitated and underwent electrophysiological study and catheter ablation of
      the accessory pathway (AP). In a control (group B) of five patients with manifest
      AP, sustained AF was induced by rapid atrial pacing during electrophysiological
      study and 12 mg of adenosine was administered. The ECG and electrophysiologic
      features in the two groups were compared. All patients had a single manifest AP.
      In group A, three patients had a left free-wall AP and one patient had a
      posteroseptal AP, while in the control group all had left free-wall APs. The
      antegrade AP effective refractory period (ERP) in groups A and B was 227 +/- 29
      and 289 +/- 37 ms, respectively (P < 0.05). The atrial ERP was 210 +/- 17 versus
      219 +/- 21 ms, respectively, in groups A and B (P > 0.05). The shortest R-R
      interval during AF in group A was 246 +/- 51 ms and 301 +/- 60 ms in group B (P
      value < 0.05). After adenosine, no patient in group B developed VF. Adenosine may
      cause VF when administered during preexcited AF. This phenomenon is seen in
      patients having APs with short refractory periods.

PMID- 11991374
TI  - Common atrial flutter sustained by a right atrial circus movement with
      anticlockwise rotation: the first demonstration in humans.

PMID- 11991375
TI  - Relation between the pacing induced sequence of activation and left ventricular
      pump function in animals.
AB  - The main goal of this article was to review animal experimental work on the
      effect of asynchronous activation on ventricular pump function. During normal
      sinus rhythm and atrial pacing, the Purkinje system contributes significantly to
      the rapid electrical activation of the ventricles. In contrast, during
      ventricular pacing the impulse is almost exclusively conducted through the normal
      myocardium. As a consequence, electrical activation of the ventricles becomes
      asynchronous and has an abnormal sequence. The abnormal impulse conduction causes
      considerable disturbances to occur in regional systolic fiber shortening,
      mechanical work, blood flow, and oxygen consumption; low values occurring in
      early activated regions and values above normal being present in late activated
      regions. Many animal studies have now shown that the abnormal electrical
      activation, induced by ventricular pacing, leads to a depression of systolic and
      diastolic LV function. Pacing at the right ventricular apex (the conventional
      pacing site) reduces LV function more than pacing at the high ventricular septum
      or at LV sites. In canine hearts with experimental LBBB, LV pacing significantly
      improves LV pump function. Differences in LV pump function between (combinations
      of) pacing sites are poorly correlated with QRS duration. Therefore, the cause of
      the depression of LV function during abnormal electrical activation appears to be
      a combination of the asynchrony and the sequence of activation. These
      experimental findings justify continuing attention for optimizing the site(s) of
      ventricular pacing in patients with normal and abnormal ventricular impulse
      conduction.

PMID- 11991376
TI  - Assessment of noise in digital electrocardiograms.
AB  - Technically related noise in 12-lead ECGs recorded with ambulatory recorders has
      never been systematically compared with that in ECGs recorded with conventional
      ECGs. This study compared serial 10-second ECGs obtained in ten healthy men, age
      22-45 years, who were recorded in the supine resting position using a (1) MAC VU
      recorder, (2) digital ambulatory SEER MC recorder with a Multi-Link detachable
      ECG cable, and (3) digital ambulatory SEER MC recorder with a light ambulatory
      ECG cable. In each ECG, averaged sinus rhythm cycles of the entire recording were
      realigned with the native signal and subtracted. The resulting "residuum" was
      quantified by computing its standard deviation and root mean square of successive
      differences (RMSSD). While the RMSSD residuum values were significantly lower
      with the MAC VU recorder (6.27 +/- 0.98 microV) than with the SEER MC recorder
      with either ECG cables (7.29 +/- 1.31 and 7.17 +/- 1.31 microV, P < 0.003 and p <
      0.02), the difference was practically negligible and there was no detectable
      difference in the standard deviation residuum values. The study concludes that
      valid ECG investigations of serial ECG testing may be conducted using the
      ambulatory SEER MC recorders providing the biological sources of ECG noise are
      controlled. The available technology for noise assessment suggests that studies
      involving advanced analysis of serial ECGs (e.g., of drug related changes),
      should incorporate objective characterisation of ECG quality.

PMID- 11991377
TI  - Unexpected ventricular asystole in a DDD pacemaker: what is the mechanism?

PMID- 11991378
TI  - Mexiletine related chronic defibrillation threshold elevation: case report and
      review of the literature.
AB  - Many antiarrhythmic drugs may produce a rise in defibrillation threshold.
      Mexiletine is a frequently used antiarrhythmic drug in patients with an
      implantable cardioverter defibrillator, usually thought of as producing no or
      minimal effects on the defibrillation threshold. The current case report presents
      a patient with an endocardial implantable cardioverter defibrillator being
      treated with mexiletine, which precluded the ability to defibrillate the patient.

PMID- 11991379
TI  - An unusual case of pacemaker failure: complete disconnection of connector block
      and battery of a subpectorally implanted dual chamber pacemaker.
AB  - Local trauma to patients with implanted pacemaker devices may result in lead
      fracture or breakage of the lead socket with leakage of fluid into the connector
      system. This report describes an unusual case of complete entrance and exit block
      in a subpectorally implanted dual chamber pacemaker due to total disconnection
      and dislodgement of header block and battery part. Damage may be caused by an
      interaction of machine fatigue/manufacturing defective and fixation of the header
      with unusual movability of the battery, leading to breakage with intermittent
      malfunction and consecutive bradycardia and syncope.

PMID- 11991380
TI  - Intoxication with taxus baccata: cardiac arrhythmias following yew leaves
      ingestion.
AB  - The use of yew leaves (Taxus Baccata) as a means of deliberate self-harm is
      infrequent. The potent effect of the toxin is primarily cardiac and results in
      rhythm alterations and ultimately ventricular fibrillation. As there is no known
      antidote, and classic antiarrhythmic therapy proves to be ineffective, a prompt
      diagnosis is of great importance as immediate supportive action is the only
      valuable alternative. This case describes a 43-year-old women who attempted
      suicide by ingesting the leaves of Taxus Baccata. We discuss the effects and the
      difficulty of treatment associated with yew leaf poisoning.

PMID- 11991381
TI  - Brugada syndrome: a case report of an unusual association with vasospastic angina
      and coronary myocardial bridging.
AB  - This report describes a case of an unusual association between vasospastic
      angina, coronary myocardial bridging, and Brugada syndrome. The patient
      complained of chest pain followed by rhythmic palpitation and syncope. Brugada
      syndrome ECG markers were documented with transient ST-segment elevation in
      lateral leads. A coronary angiogram showed a myocardial bridging in the left
      anterior descending artery and coronary vasospasm was reproduced after
      intracoronary ergonovine injection in the circumflex coronary artery. Ventricular
      fibrillation was induced by programmed electrical stimulation. The described
      association can be important because interaction between ischemia and Brugada
      syndrome electrophysiological substrate could modulate individual susceptibility
      to life-threatening ventricular tachyarrhythmias.

PMID- 11991382
TI  - Rhabdomyolysis induced by repeated internal cardioverter defibrillator
      discharges.

PMID- 11991383
TI  - Inadvertent detection of 60-Hz alternating current by an implantable cardioverter
      defibrillator.
AB  - A patient with an ICD received therapies from his ICD while exercising in an
      indoor swimming pool. Interrogation of the ICD revealed inappropriate detection
      of 60-Hz alternating current artifact and delivery of ICD therapies.

PMID- 11991384
TI  - The STIMAREC Bulletin.

PMID- 11991385
TI  - Involvement of steroid hormones on in vitro maturation of pig oocytes.
AB  - The purpose of this study was to determine if the addition of steroid hormones
      into the culture medium could influence the in vitro maturation of pig oocytes.
      The cumulus-oocyte complexes (COCs). collected from follicles of 2-5 mm diameter,
      were matured in steroid-free medium supplemented with various concentrations of
      estradiol-17beta (0-3000 ng/ml), progesterone (0-5000 ng/ml) and testosterone (0
      300 ng/ml). The COCs were cultured for 42 h, then fertilized in vitro. We
      analyzed nuclear and cytoplasmic maturation with lacmoid stain 20 h after in
      vitro insemination. We observed no significant effect (P > 0.05) on the
      percentage of oocytes completing nuclear or cytoplasmic maturation or the number
      of sperm penetrating each oocyte for any concentration of progesterone, estradiol
      17beta or testosterone. Similarly, adding a combination of those hormones to the
      medium did not significantly (P > 0.05) affect any of the criteria. In order to
      determine if there was a possible secretion of steroids during maturation, we
      added COCs, denuded oocytes and stripped cumulus cells to drops of a steroid-free
      medium and cultured them for 42 h, after which we analyzed the medium, before and
      after culture, for the presence of progesterone, estradiol-17beta and
      testosterone by radioimmunoassay (RIA) analysis. COCs, as well as cumulus cells
      alone, secreted similar amounts of estradiol (43.3 and 37.5 pg/ml, respectively)
      and progesterone (4.24 and 4.79 ng/ml, respectively) into the maturation medium.
      A small amount of estradiol (28.8 pg/ml) was also detected when oocytes were
      cultured alone. These results indicate that no steroids need to be added to the
      maturation medium of pig oocytes and that the COCs secrete steroids during
      maturation. It is possible that the amounts produced by the COCs fulfill any
      requirement for steroids if these steroids are required for either nuclear or
      cytoplasmic oocyte maturation.

PMID- 11991386
TI  - Effect of different extenders and storage temperatures on sperm viability of
      liquid ram semen.
AB  - Semen was collected with an artificial vagina from four adult rams. The
      ejaculates were pooled and diluted, using a split-sample technique, in four
      different extenders: one for milk (Mi), one for sodium citrate (Na), and two for
      Tris-based extenders (T1 and T2) including egg yolk. Thereafter, the diluted
      semen was stored at 5 and 20 degrees C, respectively. We evaluated sperm
      viability after 0, 6, 12, 24 and 30 h of storage. We assessed sperm motility
      subjectively, and we determined sperm membrane integrity using both the hypo
      osmotic resistance test (ORT) and a fluorophore staining (SYBR-14 and propidium
      iodide) technique. We evaluated acrosomal status with Spermac and capacitation
      status with Chlortetracycline (CTC assay). All sperm viability parameters were
      influenced by storage time and extender, while sperm motility was the only
      evaluated parameter that was influenced by the interaction between extender and
      temperature. Semen that was diluted and stored in the commercially available Tris
      based extender (T2) maintained sperm motility for a longer period of time, and
      acrosome and membrane integrity was higher during storage for up to 30 h as
      compared to the other extenders independent of storage temperature. In general,
      however, storage of ram semen at 5 degrees C seemed to influence sperm viability
      parameters less than storage at 20 degrees C. In conclusion, the results of the
      present study indicate that Tris-based extenders, especially T2, preserved sperm
      viability better than both the sodium citrate- and the milk-based extender did
      when liquid ram semen was stored up to 30 h at 5 and 20 degrees C. Whether the
      differences found between the extenders will be reflected in the fertility
      results after AI is yet unknown and needs to be further studied.

PMID- 11991387
TI  - Administration of prostaglandin F2alpha after farrowing alters the association
      between lactation length and subsequent litter size in mid- or old-parity sows.
AB  - A 4000 sow farm in the US using early weaning and a computerized record system
      was recruited. Farrowed sows were assigned into two experimental treatments:
      prostaglandin F2alpha injection or control. Sows were assigned by a farm worker
      to obtain even parity distributions between two groups in each farrowing group. A
      single i.m. injection of 2 ml of prostaglandin F2alpha between 24 and 48 h after
      farrowing was administered in the muscle immediately lateral to the vulva.
      Control sows received no treatment. Of 3562 farrowed sows, 1592 were administered
      with prostaglandin F2alpha. Parity distributions were not different between
      control and treatment groups. Parity was categorized into two groups: parity 1-2
      or > or = 3. Mean lactation length was 18 days and there was no difference
      between the control and treatment groups. No main effects of prostaglandin
      F2alpha administration were found in either parity group on adjusted 21-day
      litter weight, weaning-to-first-mating interval or weaning-to-conception
      interval. In parity > or = 3 sows, a two-way interaction between the association
      of lactation length and treatment with pigs born alive at subsequent farrowing
      was found (P = 0.044), while no such interaction was found in parity 1-2 sows (P
      = 0.14). The prediction line for subsequent pigs born alive indicates that
      prostaglandin F2alpha administration alters the relationship between lactation
      length and subsequent litter size on mid- or old-parity sows.

PMID- 11991388
TI  - In vitro spontaneous parthenogenetic activation of golden hamster oocytes.
AB  - Parthenogenetic activation is a major hurdle to be cleared for the examination of
      the human sperm chromosome after intracytoplasmic injection (ICSI) into golden
      hamster oocytes. Various factors that affect spontaneous activation of hamster
      oocytes were, therefore, investigated in this study. We collected cumulus-oocyte
      complexes (COC) from the oviducts of superovulated females and washed them
      thoroughly with Ca2+-containing or Ca2+-free TALP-HEPES medium (handling media).
      We cultured oocytes with intact cumulus or those without cumulus (removed by
      previous hyaluronidase treatment) in Ca2+-containing or -free m-TALP-3 for 6 or
      12 h before examining for their activation. Among the oocytes recovered 17 h post
      hCG, 92-94% were parthenogenetically activated by 6 h of in vitro culture.
      Activation rate in the oocytes collected at 13.5 h post-hCG (53%) was
      significantly (P < 0.05) lower than that in the oocytes collected 17 h post-hCG
      (92%), indicating that the spontaneous activation rate increased as the oocytes
      became older. Both cumulus-intact and cumulus-free oocytes had similar (P > 0.05)
      activation rates when cultured in vitro, suggesting that hyaluronidase treatment
      had no effect on the rate of oocyte activation. Omission of Ca2+ from the
      handling medium also had no effect on the activation of the oocytes. The rate of
      spontaneous activation of the oocytes cultured in calcium-free medium for 6 (9%)
      and 12 h (16%) was significantly (P < 0.01) lower than that (94%) of the control
      oocytes cultured in Ca2+-containing medium, implying a positive influence of Ca2+
      on in vitro activation of hamster oocytes. When we cultured the oocytes first in
      calcium-free medium for 6 h, and then in calcium-containing medium for 6 h, 94%
      were activated, which is comparable to the rate for oocytes continuously cultured
      in Ca2+-containing medium. This indicates that the inhibition of hamster oocyte
      activation in Ca2+-free medium is reversible and can be used to control
      spontaneous activation of golden hamster oocytes.

PMID- 11991389
TI  - Synchronization of estrus in virgin beef heifers using melengestrol acetate and
      PGF2alpha: an efficacy comparison of cloprostenol and dinoprost tromethamine.
AB  - This study compared the efficacy of two sources of PGF2alpha on the reproductive
      performance of virgin beef heifers, after synchronization of estrus using
      melengestrol acetate (MGA) and PGF2alpha. Angus-based heifers (n = 1002) in five
      herds were fed 0.5 mg per head per day of MGA for 14 days. Nineteen days after
      the last day of MGA feeding, heifers were randomly assigned to receive (i.m.)
      either 0.5 mg cloprostenol (n = 504; Estrumate, E) or 25 mg dinoprost
      tromethamine (n = 498; Lutalyse, L) as a source of exogenous PGF2alpha. Heifers
      were observed twice daily for 5 days for signs of estrus and artificially
      inseminated 8-12 h later, except in herd A, wherein animals not detected in
      estrus by 80 h after PGF2alpha were mass-mated and no longer monitored for signs
      of estrus. Estrumate and Lutalyse were equally (P > 0.1) effective among all
      response variables evaluated, including estrus response (E, 89% and L, 86%),
      conception rate (E, 67% and L, 67%), and synchronized pregnancy rate (E, 61% and
      L, 57%). Synchrony of estrus was not affected (P > 0.1) by PGF2alpha source, and
      peak estrus response occurred 60 h post-PGF for both treatments. Conception rate
      to timed insemination was not different (P > 0.1) among Estrumate- and Lutalyse
      treated heifers within herd A (14%, 4/28 and 7%, 2/29, respectively). Herd had a
      significant (P < 0.05) effect on all indicators of reproductive performance.
      Conception rates within herds A and D were influenced by technician (P < 0.05),
      however, this effect was balanced across treatments and no treatment by
      technician interaction was detected. In conclusion, when administered 19 days
      after a 14-day MGA feeding period, cloprostenol and dinoprost tromethamine are
      equally efficacious for synchronous induction of a fertile estrus in virgin beef
      heifers.

PMID- 11991390
TI  - Effect of dietary supplementation with a mixture of Vitamins C and E on
      fertilization of tertiary butyl hydroperoxide-treated oocytes and parthenogenetic
      activation in the mouse.
AB  - The present study aims to analyze the effect of dietary supplementation with a
      mixture of Vitamins C and E on fertilization and later development of tertiary
      butyl hydroperoxide (tBH)-treated mouse oocytes and on parthenogenetic activation
      of freshly ovulated mouse oocytes. We fed hybrid mice a standard diet
      supplemented or not supplemented with Vitamins C and E from the first day of
      weaning until the age of 12 weeks. We noted no significant effect of diet on
      fertilization rate, percentage of total and hatching blastocysts, total number of
      cells, mitotic index and percentage of apoptotic nuclei at 120 h post
      insemination of oocytes incubated for 15 min in the presence of 0, 1, 5 and 10
      microM tBH. Furthermore, diet did not affect the percentage of activated oocytes
      after treatment with Ca2+ ionophore, acid Tyrode's solution or ethanol. The
      percentage of parthenogenetically activated oocytes that progressed to the
      pronuclear stage was significantly higher in the antioxidant group. Oocytes from
      antioxidant females exhibited a significantly lower mitogen-activated protein
      kinase (MAPK) activity than oocytes from control females. We detected no
      significant differences between groups in M-phase-promoting factor (MPF)
      activity. These results show that oral administration of antioxidants decreases
      MAPK activity and increases the probability of reaching the pronuclear stage
      after parthenogenetic activation.

PMID- 11991391
TI  - Litter size and piglet traits of gilts with different prolactin receptor
      genotypes.
AB  - Seventy-seven Large White x Meishan F2 crossbred gilts with prolactin receptor
      (PRLR) genotype AA (n = 26), AB (n = 36) and BB (n = 15) were compared for teat
      number (FTm), age at first estrus, gestation length (GL), litter size, and litter
      means of functional teat number (FTp), birthweight (BW), and pre-weaning growth
      rate (GR). Own placental information was available for 88% of 620 live-born
      piglets (62 gilts), since placentae were labeled during farrowing. The effect of
      PRLR genotype of the mother on average placenta weight (PLW) and placenta
      efficiency (EFF = BW/PLW), was therefore, also analyzed, PRLR genotype
      significantly (P < 0.05) affected age at first estrus and, as a result (since the
      gilts were inseminated at a fixed estrus number), age and bodyweight at
      insemination. Furthermore, PRLR genotype affected total number of piglets born
      (TNB, P = 0.056) and number of piglets born alive (NBA, P = 0.072), but it did
      not affect (P > 0.3) GL, BW or GR, neither before nor after correction for litter
      size. BB gilts were significantly younger at first estrus and younger and lighter
      at insemination than AA gilts (P < 0.05). AA gilts had larger TNB (P = 0.047) and
      tended to have a larger NBA (P = 0.062) than BB gilts. TNB was 11.4 +/- 0.7, 10.8
      +/- 0.6, and 8.8 +/- 0.9; NBA was 11.1 +/- 0.6, 10.5 +/- 0.6, and 8.7 +/- 0.9; BW
      was 1309 +/- 40, 1277 +/- 34, and 1290 +/- 53 g; and GL was 113.6 +/- 0.3, 113.8
      +/- 0.3, and 113.5 +/- 0.4 days for AA, AB and BB gilts, respectively. The
      effects on litter size and age at first estrus are independent effects. PRLR
      affected PLW (P = 0.050) and EFF (P = 0.066), resulting in a difference between
      AA and BB gilts. PLW was 160 +/- 9, 181 +/- 7 and 196 +/- 11 g and EFF was 7.6 +/
      0.2, 7.3 +/- 0.2 and 6.7 +/- 0.3 for AA (n = 19), AB (n = 29) and BB (n = 14)
      gilts, respectively. After correction for TNB, the differences disappeared.
      Functional teat number of the AA. AB and BB gilts was 15.35 +/- 0.22, 15.53 +/-
      0.18, and 15.60 +/- 0.29, respectively, and was not affected by PRLR genotype (P
      = 0.7). Functional teat number of piglets from AA, AB and BB mothers was 14.20 +/
      0.10, 14.37 +/- 0.08, and 14.63 +/- 0.13, respectively. Piglets from BB mothers
      had on average larger numbers of functional teats compared to piglets from AA
      mothers (P = 0.028). In conclusion, PRLR gene is a major gene or marker for age
      at first estrus, litter size, and litter average of number of functional teats in
      the Large White x Meishan F2 crossbred gilts studied. The favorable allele for
      litter size (A allele) is the unfavorable allele for age at first estrus and for
      litter mean of functional teat number.

PMID- 11991392
TI  - Effects of growth hormone and insulin-like growth factor-I on development of in
      vitro derived bovine embryos.
AB  - The objectives of this study were to determine whether the addition of growth
      hormone (GH) to maturation medium and GH or insulin-like growth factor-I (IGF-I)
      to culture medium affects development of cultured bovine embryos. We matured
      groups of 10 cumulus-oocyte complexes (COCs) in serum-free TCM-199 medium
      containing FSH and estradiol with or without 100 ng/ml GH. After fertilization,
      we transferred groups of 10 putative zygotes to 25 microl drops of a modified
      KSOM medium containing the following treatments: non-specific IgG (a control
      antibody, 10 microg/ml); GH (100 ng/ml) + IgG (10 microg/ml, GH/IgG); IGF-I (100
      ng/ml) + IgG (10 microg/ml, IGF/IgG); antibody to IGF-I (10 microg/ml, anti-IGF);
      GH (100 ng/ml) + anti-IGF (10 microg/ml GH/anti-IGF); IGF-I (100 ng/ml) + anti
      IGF (10 microg/ml, IGF/anti-IGF); no further additions (control). We repeated the
      experiment six times. Adding GH to the maturation medium increased cleavage rates
      at Day 3 compared to control (87.3 +/- 1.2% > 83.9 +/- 1.2%; P < 0.05) but had no
      effects on blastocyst development at Day 8. At Day 8, blastocyst development was
      greater (P < 0.01) for GH/IgG (24.8 +/- 2.5%) and IGF/IgG (33.7 +/- 2.5%) than
      for IgG (16.1 +/- 2.1%) and greater for IGF/IgG than for GH/IgG (P < 0.02).
      Blastocyst development at Day 8 did not differ between anti-IGF (20.4 +/- 1.8%)
      and GH/anti-IGF (24.1 +/- 1.9%) or IGF/anti-IGF (17.7 +/- 1.9%), but it was
      greater for GH/anti-IGF than for IGF/anti-IGF (P < 0.05). The Day 8 blastocysts
      of GH/IgG and IGF-I/IgG groups had a higher (P < 0.01) number of cells than the
      IgG group. The addition of anti-IGF-I eliminated the effects of IGF-I on cell
      number but did not alter GH effects. In conclusion, both GH and IGF-I stimulate
      embryonic development in cattle and GH effects may likely involve IGF-I
      independent mechanisms.

PMID- 11991393
TI  - Effect of preparing and loading multiple insemination guns on conception rate in
      two large commercial dairy herds.
AB  - In large herds, inseminators frequently thaw multiple straws of semen and prepare
      several insemination guns at once. The aim of this study was to measure the
      effect of breeding order, the order that thawed straws are used, on conception
      rate in commercial dairy herds. A single professional inseminator, utilizing
      semen from five suppliers, performed 2629 inseminations over 30 months. Up to
      four straws were thawed at one time with the restriction that straws were used
      within 20 min of thawing. Straws were thawed per supplier's recommendations, with
      66.4% of the straws pocket thawed and the remainder warm-water thawed. Conception
      was determined by a pregnancy check at 42 days. Data were modeled by multiple
      logistic regression analysis, which included herd, breeding order, lactation
      number, times bred, month bred and year bred. Breeding order had no significant
      effect on the probability of conception: Cows 1-4 achieved adjusted conception
      rates of 0.36, 0.41, 0.37, and 0.39, respectively. Odds ratios (and 95%
      confidence intervals) were 1.00 (1.00-1.00), 1.22 (0.99-1.49), 1.04 (0.82-1.32),
      and 1.12 (0.86-1.45), respectively. Associated laboratory studies, which
      evaluated the effect of post-thaw holding time on percentage of sperm with
      progressive motility, found mean values at 20 min holding time to be largely
      unchanged from mean values at 5 min. Thawing temperatures were 6, and 35 degrees
      C and holding temperatures were 6, 22, and 35 degrees C. The length of the trial
      and the wide use of semen from multiple suppliers with differing thawing methods
      suggests that under similar conditions, a careful and experienced inseminator can
      thaw multiple straws of semen and prepare insemination guns sufficient to breed
      up to four cows within 20 min, without an adverse effect on conception.

PMID- 11991394
TI  - Reproductive performance of Friesian mares after retained placenta and manual
      removal of the placenta.
AB  - Because the incidence of retained placenta in Friesian mares is estimated to be
      high, and no reports have been published on the reproductive performance of
      Friesian mares after retained placenta, we studied postpartum reproductive
      performance in Friesian brood mares with (n = 54) and without (n = 50) retained
      placenta. We defined a retained placenta as the failure to expel all fetal
      membranes within 3 h after the delivery of a foal. We subdivided the group of
      mares with retained placenta into mares in which the placenta had been removed
      manually (n = 30) and mares in which it had not (n = 24). Within each group, we
      compared reproductive performance after breeding in the foal heat and breeding in
      a subsequent heat. We also recorded the age of the mares, number of mares treated
      with antibiotics after insemination, and number of mares treated with
      prostaglandins. The interval between delivery and conception, efficacy rate
      (number of served cycles divided by the number of mares that had a positive
      pregnancy diagnosis), seasonal pregnancy rate, pregnancy rate after first
      insemination, pregnancy loss rate, and foaling rate did not differ between mares
      with and without retained placenta or between mares with and without manual
      removal of the retained placenta. Within each group, the pregnancy rate after
      first insemination did not differ between breeding for the first time in the foal
      heat and breeding for the first time in a subsequent heat. We concluded that
      reproductive performance did not differ between (1) Friesian mares with and
      without retained placenta and (2) Friesian mares with and without manual removal
      of the placenta. With regard to reproductive performance, retained placenta and
      manual removal of the placenta are not valid reasons to avoid foal heat breeding
      in Friesian mares.

PMID- 11991395
TI  - Presence of caprine arthritis-encephalitis virus (CAEV) infected cells in
      flushing media following oviductal-stage embryo collection.
AB  - To improve the knowledge on the risk of transmission of the caprine arthritis
      encephalitis virus (CAEV) during embryo manipulations, we conducted a double
      nested polymerase chain reaction (PCR) for CAEV proviral-DNA on flushing media
      recovered from the oviducts 48 h after the beginning of estrus and on blood from
      89 donor does. Sixty-four does had negative blood and flushing media by PCR.
      Among the 25 CAEV infected goats (blood PCR positive), 11 were PCR flushing media
      positive (P < 0.01). Cell lysate from flushing media samples that were PCR
      positive were serially diluted 10 times at 1:100. Starting with the second 1:100
      dilution all the cell lysate samples were PCR negative. The mean number of
      embryos recovered was not significantly different between goats with flushing
      media PCR positive and goats with flushing media PCR negative (6.0 +/- 5.4 versus
      7.8 +/- 4.4, respectively; mean +/- S.D.) nor between goats with blood PCR
      positive and goats with blood PCR negative (7.0 +/- 5.0 versus 5.9 +/- 5.3; mean
      +/- S.D.). The presence of CAEV infected cells in oviductal flushing media from
      infected donor does was indicated for the first time during this study. The
      absence of flushing media PCR positive for goat blood PCR negative seemed to
      allow the use of the blood PCR test to confidently predict the absence of CAEV
      provirus in the oviductal fluid.

PMID- 11991396
TI  - Serum calcium and magnesium concentrations and the use of a calcium-magnesium
      borogluconate solution in the treatment of Friesian mares with retained placenta.
AB  - The purpose of the present study was to compare serum calcium and magnesium
      concentrations in mares with or without a retained placenta (RP) and to evaluate
      treatment of mares with RP with oxytocin versus oxytocin combined with Ca-Mg
      borogluconate solution. Blood samples were obtained within 12 h of foaling from
      Friesian mares with and without an RP (n = 90 and 65, respectively). Serum Ca and
      Mg concentrations were analyzed by atomic absorption spectrophotometry. In total,
      we treated 112 cases of RP in 101 Friesian mares by infusion of either oxytocin
      dissolved in saline solution or oxytocin dissolved in Ca-Mg-borogluconate
      solution. We defined RP as the failure to expel all or a part of the fetal
      membranes up to 3 h after delivery of the foal. We defined a positive response to
      the treatment as the passage of the entire placenta within 2 h after the
      infusion. Mares with RP had significantly lower serum calcium levels within 12 h
      of foaling than mares without RP. Serum magnesium levels showed no difference.
      Sixty-four percent of the mares treated with oxytocin in Ca-Mg-borogluconate
      solution responded positively to the treatment, compared to 44% of the mares
      treated with oxytocin in saline solution (P < 0.05).

PMID- 11991397
TI  - Milk yield, energy balance, hormone, follicular and oocyte measures in early and
      mid-lactation Holstein cows.
AB  - The purpose of the study was to determine the influence of energy status on
      metabolic and endocrine measures, follicular development, and the quality of
      oocytes obtained from cows during early and mid-lactation (ML). We selected
      Holstein cows at calving to be assigned to the early lactation (EL) group (n =
      8), while we assigned cows at about day 90 postpartum to the ML group (n = 7). We
      obtained blood samples twice weekly from 4 weeks before aspiration to the
      aspiration periods for metabolite and hormone determinations. We performed
      ultrasound-guided transvaginal follicular aspiration (TVFA) twice weekly on all
      cows for a 10-week period. We obtained follicular fluid from the largest follicle
      > 10 mm in diameter for hormone determinations. We analyzed data by ANOVA, using
      the general linear model (GLM) procedures. Energy balance was positive (2.43 +/-
      0.32 Mcal/kg) for ML cows and negative (-1.55 +/- 0.33 Mcal/kg) for EL cows.
      Serum progesterone (P4) for ML cows decreased rapidly from the first aspiration
      session (2.7 +/- 0.1 ng/ml) and reached a nadir at Week 8 (0.33 +/- 0.1 ng/ml),
      while follicular fluid P4 increased from 0.9 +/- 0.5 to 5.6 +/- 0.05 ng/ml. Serum
      and follicular fluid P4 remained relatively constant over the entire aspiration
      period for EL cows. Follicular fluid insulin-like growth factor I (TGF-I)
      concentrations increased linearly for EL and ML cows, but the increase was more
      rapid (159 +/- 36 to 200 +/- 36 ng/ml) for ML cows than for EL cows (145 +/- 36
      to 164 +/- 36 ng/ml). Serum IGF-I followed the same pattern for ML cows but
      declined for EL cows. Early lactation cows experienced a rapid decrease in serum
      nonesterified fatty acids (NEFA; 0.32 +/- 0.2 to 0.22 +/- 0.2 meq/l), while serum
      NEFA concentrations were relatively stable (0.19 +/- 0.2 to 0.22 +/- 0.2 meq/l)
      for ML cows over the aspiration period. The number of follicles obtained from the
      twice weekly aspiration sessions increased linearly for both EL and ML cows (P <
      0.05) over the 10-week period. However, the number of follicles increased from
      14.2 +/- 0.5 (Day 119) to 18.1 +/- 0.5 (Day 190) in the ML cows, compared to the
      changes from 14.9 +/- 0.3 (Day 32) to 15.7 +/- 0.5 (Day 90) for the EL cows.
      These results indicate that cows are physiologically under more production stress
      during EL, but increasing follicular fluid and serum IGF-I throughout ML may
      reflect potential differences in follicle and oocyte measures, compared to cows
      in EL.

PMID- 11991398
TI  - Characterization of PH-20 in canine spermatozoa and testis.
AB  - The purpose of this study was to characterize the sperm membrane protein PH-20 in
      the dog. Canine spermatozoa were extracted with Triton X- 100 and the presence of
      PH-20 was determined by immunoblot with an antibody against recombinant macaque
      PH-20. The hyaluronidase activity of canine PH-20 was determined with substrate
      gel electrophoresis based upon digestion of hyaluronic acid (HA) incorporated
      into the separating gels. Hyaluronidase activity was also quantified using a
      microplate assay. Sperm extracts were incubated at pH 4 or 7 in wells containing
      agarose and HA. For immunolabeling of PH-20 on canine sperm membranes, canine
      sperm were fixed and incubated with R-10 primary antibody, and an anti-rabbit IgG
      FITC secondary antibody. Samples were visualized by fluorescence microscopy. Non
      reducing SDS-PAGE and Western blot of detergent-extracted canine sperm revealed a
      major band at 50 kDa, and three other bands at 42, 124, and >209 kDa. Substrate
      PAGE revealed translucent bands of hyaluronidase activity of similar size to
      bovine testicular hyaluronidase. These bands were markedly more pronounced at pH
      4 than at pH 7. The microplate assay also demonstrated that hyaluronidase
      activity was over four times greater at the acidic pH. Immunolabeling of canine
      spermatozoa demonstrated that PH-20 is localized to the anterior head region and
      appeared in the Golgi area of round spermatids as detected by the
      immunohistochemical staining of the testis. This study provides evidence that PH
      20 is present on the membrane of canine spermatozoa and in round spermatids.
      Canine PH-20 exhibits hyaluronidase activity that is markedly more pronounced at
      acidic pH.

PMID- 11991399
TI  - Uterine involution, day and variance of first postpartum ovulation in mares
      treated with progesterone and estradiol-17beta for 1 or 2 days postpartum.
AB  - The effects of a single or double regimen of exogenous progesterone and estradiol
      17beta (P/E, total dose 300 mg P/20 mg E) were investigated in 50 postparturient
      Quarter Horse mares. In Trial 1, at 1 and 24 h after foaling, mares were injected
      with progesterone (150 mg) and estradiol-17beta (10 mg) (n = 7) or 0.9% NaCl
      (control, n = 13). In Trial 2, within 12 h after foaling, mares were injected
      with progesterone (300 mg) and estradiol-17beta (20 mg) (n = 13) or 0.9% NaCl
      (control, n = 17). Mares were examined daily by palpation per rectum and
      transrectal ultrasonography to determine the day of ovulation. The largest cross
      sectional diameters of each uterine horn and uterine body were measured
      ultrasonographically on Day 15 postpartum. Mean uterine diameters did not differ
      between treatment groups (P > 0.05) in Trial 1, Trial 2 or for combined data for
      both Trials 1 and 2. For mares bred on the first postpartum estrus pregnancy
      rates did not differ (P > 0.05) between treatment groups (16/18, 89%) and
      controls (22/30, 81%) nor was there a difference in mean day to first postpartum
      ovulation (P > 0.05) between treated and control groups in Trial 1, Trial 2 or
      Trials 1 and 2 combined. However, fewer (P < 0.05) total P/E treated mares (0/20)
      ovulated prior to Day 10 postpartum than did control mares (6/30). Variance in
      days to ovulation was lower (P < 0.05) for P/E treated mares (var = 3.73 days)
      than for control mares (var = 7.64 days) for data combined from Trials 1 and 2.

PMID- 11991400
TI  - Health care options for small business owners would expand under proposal before
      Congress.

PMID- 11991401
TI  - The rationale for ridding U.S. of scrapie.

PMID- 11991402
TI  - Are you ready for producers' questions about the scrapie program?

PMID- 11991403
TI  - About scrapie.

PMID- 11991404
TI  - What is your diagnosis? Multiple metallic objects, presumed to be BB pellets, in
      the soft tissues surrounding the pelvis and near the penile urethra.

PMID- 11991405
TI  - Stray voltage in the dairy barn.

PMID- 11991406
TI  - Evaluation of the scientific justification for tail docking in dairy cattle.

PMID- 11991407
TI  - Gender and work: what veterinarians can learn from research about women, men, and
      work.

PMID- 11991408
TI  - Effects of diet restriction on life span and age-related changes in dogs.
AB  - OBJECTIVE: To evaluate the effects of 25% diet restriction on life span of dogs
      and on markers of aging. DESIGN: Paired feeding study. ANIMALS: 48 Labrador
      Retrievers. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less
      food than its pair-mate from 8 weeks of age until death. Serum biochemical
      analyses were performed, body condition was scored, and body composition was
      measured annually until 12 years of age. Age at onset of chronic disease and
      median (age when 50% of the dogs were deceased) and maximum (age when 90% of the
      dogs were deceased) life spans were evaluated. RESULTS: Compared with control
      dogs, food-restricted dogs weighed less and had lower body fat content and lower
      serum triglycerides, triiodothyronine, insulin, and glucose concentrations.
      Median life span was significantly longer for dogs in which food was restricted.
      The onset of clinical signs of chronic disease generally was delayed for food
      restricted dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that 25%
      restriction in food intake increased median life span and delayed the onset of
      signs of chronic disease in these dogs.

PMID- 11991409
TI  - Bacterial colonization of intravenous catheters in young dogs suspected to have
      parvoviral enteritis.
AB  - OBJECTIVE: To determine the prevalence of bacterial colonization of IV catheters
      among young dogs suspected to have parvoviral enteritis, to identify the
      organisms responsible for catheter colonization, and to determine the
      antimicrobial susceptibility of organisms that were obtained. DESIGN: Case
      series. ANIMALS: 100 dogs. PROCEDURE: Catheters were aseptically removed when
      fluid therapy was discontinued, the catheter was replaced, or the dog died. The
      distal tip of the catheter was cut off, split open, and vortexed with sterile
      saline (0.9% NaCl) solution. The saline solution was plated on culture plates,
      which were then incubated and examined for bacterial growth every 24 hours for 72
      hours. All bacteria cultured were identified, and antimicrobial susceptibility
      was determined. RESULTS: Bacteria were isolated from 22 catheters. Most bacteria
      that were isolated were of gastrointestinal tract or environmental origin
      (Serratia odorifera, S. liquefaciens, S. marcescens, Acinobacter anitratus,
      Citrobacter freundii, Klebsiella pneumoniae, K. oxytoca, Escherichia coli,
      Enterobacter spp). Only 2 gram-positive organisms were isolated (Staphylococcus
      intermedius and Streptococcus spp). High percentages of organisms were resistant
      to penicillin, lincomycin, cloxacillin, erythromycin, and cephalexin. Percentages
      of organisms resistant to amikacin, enrofloxacin, chloramphenicol, potentiated
      sulfonamides, and amoxicillin-clavulanic acid were low. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that IV catheters may be colonized with bacteria in
      22% of young dogs suspected to have parvovirus infection.

PMID- 11991410
TI  - Effects of postoperative rehabilitation on limb function after cranial cruciate
      ligament repair in dogs.
AB  - OBJECTIVE: To determine the effects of early postoperative rehabilitation on limb
      function in dogs after surgery for ruptured cranial cruciate ligament (RCCL).
      DESIGN: Prospective clinical study. ANIMALS: 51 client-owned dogs. PROCEDURE:
      Dogs weighing between 20 and 40 kg (44 to 88 lb) that had RCCL and medial
      meniscal injury were studied. After removal of the RCCL and complete medial
      meniscectomy, the stifle joint was stabilized by use of a lateral retinacular
      stabilization technique. Twenty-five dogs were included in a postoperative
      rehabilitation group, and 26 dogs were included in an exercise-restricted group.
      Limb function (peak vertical force [PVF] and vertical impulse [VI]) was
      determined before surgery and 6 months after surgery, using force platform gait
      analysis. RESULTS: Prior to surgery, mean PVF and VI in affected limbs were
      similar between groups. Six months after surgery, PVF and VI were significantly
      increased in dogs of both groups. However, PVF and VI in dogs in the
      rehabilitation group were significantly greater than those of dogs in the
      exercise-restricted group. At this time, differences in limb function (as
      measured by PVF and VI) between the repaired and normal limbs were not evident in
      dogs in the rehabilitation group. Conversely, limb function in the repaired limb
      of dogs in the exercise-restricted group was still significantly less than that
      of the normal limb. CONCLUSION AND CLINICAL RELEVANCE: Dogs that have surgery for
      RCCL and a torn medial meniscus benefit from postoperative rehabilitation;
      rehabilitation should be considered part of the postoperative management of these
      patients.

PMID- 11991411
TI  - Evaluation of a commercially available luteinizing hormone test for its ability
      to distinguish between ovariectomized and sexually intact bitches.
AB  - OBJECTIVE: To determine the value of a commercially available test for
      measurement of luteinizing hormone (LH) concentrations for its use in
      distinguishing between ovariectomized and sexually intact bitches. DESIGN:
      Prospective longitudinal cohort study. ANIMALS: 101 sexually intact bitches and
      199 ovariectomized bitches PROCEDURE: A commercial test kit was used to assay
      serum samples for LH concentration. A kappa test was used to assess the
      consistency of test interpretations. Sensitivity, specificity, predictive values,
      and consistency of test interpretation in the sample population and in 2
      theoretical populations of bitches with differing frequencies of ovarian removal
      were determined. RESULTS: The test had excellent sensitivity (98%) but moderate
      specificity (78%) because of a high frequency of false-positive test results.
      This means that a single high serum LH concentration was not a reliable indicator
      of ovarian removal. However, a single low serum LH concentration was an excellent
      indicator that a bitch was sexually intact. The LH test results were positive
      within 10 days after ovarian removal and remained high in bitches from which
      ovaries had been removed > 5 years previously. Analysis of kappa values
      consistently revealed excellent agreement in test interpretation within and among
      evaluators and over a 6-hour time span. CONCLUSIONS AND CLINICAL RELEVANCE: A
      single low LH test result confirms the need for ovariectomy in bitches prior to
      adoption. The test is applicable to bitches that have been ovariectomized prior
      to puberty and probably applies over the lifespan of the animal.

PMID- 11991412
TI  - Isolation and identification of Mycobacterium kansasii from pleural fluid of a
      dog with persistent pleural effusion.
AB  - A 3-year-old spayed female Whippet was examined for cough and respiratory
      distress. Lung lobe torsion with pleural effusion was diagnosed, and lung
      lobectomy was performed. Pleural effusion recurred during the following 27
      months; conventional bacteriologic cultures of pleural effusion did not result in
      bacterial growth. A second lung lobectomy, pleuroperitoneal shunt placement. and
      pericardectomy were subsequently performed. Mycobacterium kansasii was eventually
      isolated from pleural fluid and identified by polymerase chain reaction
      amplification and DNA sequencing. The dog was euthanatized before therapeutic
      response could be evaluated. To our knowledge, this is the first report of M.
      kansasii infection in a dog. Additionally, this is the first report of
      mycobacterial isolation from pleural fluid, and one of few reports of antemortem
      mycobacterial isolation from a body fluid, as opposed to identification in
      specimens during histologic examination. Routine bacteriologic culture methods
      are insufficient to isolate mycobacterial agents, and special methods are
      indicated in dogs with persistent pleural effusion.

PMID- 11991413
TI  - Evaluation of ameroid ring constrictors for the management of single extrahepatic
      portosystemic shunts in cats: 23 cases (1996-2001).
AB  - OBJECTIVE: To document the signalment; history; clinical signs;
      clinicopathologic, diagnostic imaging, and surgical findings; perioperative
      complications; and long-term clinical results of ameroid ring constrictor (ARC)
      placement on single extrahepatic portosystemic shunts (PSS) in cats. DESIGN:
      Retrospective study. ANIMALS: 23 cats treated with an ARC on a single
      extrahepatic PSS. PROCEDURE: An ARC was placed surgically around the PSS. Portal
      pressure was measured prior to ARC placement, with complete temporary PSS
      occlusion, and after ARC placement. Cats were scheduled for recheck transcolonic
      portal scintigraphy 8 to 10 weeks after surgery. Follow-up information was
      obtained by telephone interview with the owners. RESULTS: An ARC was successfully
      placed in 22 of 23 cats. Intraoperative complications, consisting of PSS
      hemorrhage, occurred in 2 cats. Mean (+/- SD) portal pressure (n = 15) was 6.7+/
      2.9 mm Hg before PSS manipulation, 18.6+/-7.7 mm Hg with complete temporary PSS
      occlusion, and 6.9+/-2.7 mm Hg after ARC placement. Postoperative complications
      developed in 77% (17 of 22) of cats after ARC placement, and included central
      blindness, hyperthermia, frantic behavior, and generalized motor seizures.
      Perioperative mortality rate was 4.3% (1 of 23). Persistent shunting was
      identified in 8 of 14 cats. Overall, 75% (15 of 20) of cats had an excellent long
      term outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Placement of an ARC on single
      extrahepatic PSS in cats resulted in low surgical complication and perioperative
      mortality rates, but most cats did have substantial postoperative complications.
      Persistent shunting was common, although many cats with persistent shunting were
      clinically normal.

PMID- 11991414
TI  - Percutaneous collection of fetal fluids for detection of bovine viral diarrhea
      virus infection in cattle.
AB  - OBJECTIVE: To develop a method for percutaneous collection of fetal fluid from
      cattle in the late stages of gestation and determine whether bovine viral
      diarrhea virus (BVDV) can be isolated from such fluids. DESIGN: Case series.
      ANIMALS: 169 pregnant beef cattle. PROCEDURE: Animals were restrained in a
      squeeze chute, and hair was clipped from a region of the right flank. Pregnancy
      was confirmed, and fetal fluids were identified by means of abdominal
      ultrasonography. Fetal fluid was collected with a spinal needle. Virus isolation
      was performed on fetal fluids, WBC lysates from 160 live calves, and tissues from
      12 calves that died or were aborted. Blood samples collected from adult cattle
      were assayed with an immunoperoxidase monolayer assay. RESULTS: Fourteen animals
      aborted or delivered premature calves within 3 weeks after fetal fluid
      collection; however, it could not be determined whether this was a complication
      of the procedure or attributable to other factors. Results of BVDV isolation from
      fetal fluid samples were negative for 168 animals. However, a noncytopathic BVDV
      was isolated from fetal fluid obtained from a 2-year-old heifer; results of the
      immunoperoxidase assay of serum from this heifer were also positive, and a
      noncytopathic BVDV was isolated from tissue specimens from a stillborn calf
      produced by this heifer. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      fetal fluids can be collected percutaneously from cattle in the late stages of
      gestation and that virus isolation performed on fetal fluids can be used to
      identify fetuses infected with BVDV in utero. However, safety of the procedure
      could not be evaluated.

PMID- 11991415
TI  - Algal dermatitis in cichlids.
AB  - Three varieties of a popular African cichlid aquarium species, Pseudotropheus
      zebra, from 2 tropical fish farms in east central Florida were submitted for
      diagnostic evaluation because of the development of multifocal green lesions. The
      percentage of infected fish in these populations varied from 5 to 60%. Fish were
      otherwise clinically normal. Microscopic examination of fresh and fixed lesions
      confirmed algal dermatitis, with light invasion of several internal organs in
      each group. A different alga was identified from each farm. Fish from farm A were
      infected with Chlorochytrium spp, whereas fish from farm B were infected with
      Scenedesmus spp. Because of the numbers of fish involved, bath treatments to
      remove the algae from affected fish from farm B were attempted, with different
      dosages of several common algaecides including copper sulfate pentahydrate,
      diuron, and sodium chloride. However, none of these treatments were successful,
      possibly because of the location of the algae under the scales and within the
      dermis, and also because of the sequestering effect of the granulomatous
      response. To our knowledge, this is the first report of algal dermatitis in
      ornamental cichlids, as well as the first report of Scenedesmus spp infection in
      any fish.

PMID- 11991416
TI  - Survey of complications and antimicrobial use in equine patients at veterinary
      teaching hospitals that underwent surgery because of colic.
AB  - OBJECTIVE: To determine current practices regarding use of antimicrobials in
      equine patients undergoing surgery because of colic at veterinary teaching
      hospitals. DESIGN: Survey. SAMPLE POPULATION: Diplomates of the American College
      of Veterinary Surgeons performing equine surgery at veterinary teaching hospitals
      in the United States. PROCEDURE: A Web-based questionnaire was developed, and 85
      surgeons were asked to participate. The first part of the survey requested
      demographic information and information about total number of colic surgeries
      performed at the hospital, number of colic surgeries performed by the respondent,
      and whether the hospital had written guidelines for antimicrobial drug use. The
      second part pertained to nosocomial infections. The third part provided several
      case scenarios and asked respondents whether they would use antimicrobial drugs
      in these instances. RESULTS: Thirty-four (40%) surgeons responded to the
      questionnaire. Respondents indicated that most equine patients undergoing surgery
      because of colic at veterinary teaching hospitals in the United States received
      antimicrobial drugs. Drugs that were used were similar for the various hospitals
      that were represented, and for the most part, the drugs that were used were
      fairly uniform irrespective of the type of colic, whereas the duration of
      treatment varied with the type of colic and the surgical findings. The
      combination of potassium penicillin and gentamicin was the most commonly used
      treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study document the
      implementation of recommendations by several authors in veterinary texts that
      antimicrobial drugs be administered perioperatively in equine patients with colic
      that are undergoing surgery. However, the need for long-term antimicrobial drug
      treatment in equine patients with colic is unknown.

PMID- 11991417
TI  - Firearm availability and female homicide victimization rates among 25 populous
      high-income countries.
AB  - OBJECTIVE: to determine the association between firearm availability and female
      homicide victimization among high-income countries. METHODS: Data were assembled
      for the most recent available year (1994-1999) from the official reports of the
      ministries of health for those countries that had more than 2 million inhabitants
      and were dassified as high income by the World Bank. Twenty-five nations provided
      sufficient information for the analysis. Rates of female victimization from
      homicide, firearm homicide, and nonfirearm homicide were compared with a
      validated proxy for household firearm ownership (the percentage of total national
      suicides that are committed with firearms). Possible confounding variables
      included in the analysis were the percentage of the population living in urban
      areas and income inequality. RESULTS: The United States is an outlier. It had the
      highest level of household firearm ownership and the highest female homicide
      rate. The United States accounted for 32% of the female population in these high
      income countries, but for 70% of all female homicides and 84% of all female
      firearm homicides. Female homicide victimization rates were significantly
      associated with firearm availability largely because of the United States.
      CONCLUSION: Among high-income countries, where firearms are more available, more
      women are homicide victims. Women in the United States are at higher risk of
      homicide victimization than are women in any other high-income country.

PMID- 11991418
TI  - Do standard doses of frequently prescribed drugs cause preventable adverse
      effects in women?
AB  - Adverse effects from prescription medications are a leading cause of disability
      and death in the United States, and more than 75% of these adverse effects are
      dose related. This analysis examines women's experience with dose-related adverse
      effects of several major medication groups, induding oral contraceptives, hormone
      replacement therapy, anti-inflammatory drugs, antihypertensives, statins, and
      others. The original recommended doses for oral contraceptives and conjugated
      estrogens were 100% to 800% higher than the doses recommended today.
      Unnecessarily high doses of ibuprofen and terfenadine were linked to serious and
      lethal dose-related adverse effects, and proven effective lower doses of
      celecoxib, fluoxetine, omeprazole, and many other medications were not initially
      marketed or recommended. Much of the data on effective low doses of drugs is not
      readily available to physicians or patients. The lack of information on or
      recommendations for the lowest, proven-effective doses of many major medications
      may in part explain the continued high incidence of dose-related adverse effects.
      The findings in this article suggest that women, especially elderly women, may be
      prone to adverse effects linked to unnecessarily high drug doses.

PMID- 11991419
TI  - Intimate partner violence against South Asian women in greater Boston.
AB  - OBJECTIVES: to identify the prevalence of male-perpetrated intimate partner
      violence (IPV) against South Asian women (Indian, Pakistani, Bangladeshi, Sri
      Lankan, Bhutanese, Nepalese, Maldive Islanders) residing in Greater Boston; to
      identify forms of abuse, abuse-related injuries, and help-seeking behaviors of
      South Asian women reporting IPV; and to assess the relationship between current
      IPV victimization and history of nonpartner abuse, acculturation, and victim
      blaming attitudes. METHODS: A community-based volunteer sample of South Asian
      women (n=160) in relationships with male partners participated in a cross
      sectional study of women's health. Participants were recruited via community
      outreach (eg, fliers, snowball sampling, referrals) and were interviewed in
      person by trained South Asian women. RESULTS: Participants were 18 to 62 years
      old (mean age=31.6) and predominantly immigrant (87.5%); 74.4% were married,
      51.6% had children, and 71.9% had family incomes of more than $2100 per month.
      Forty percent of the sample reported physical IPV, sexual IPV, or injury/need for
      medical services due to IPV from current male partners; few women (9.4%) who
      reported ever experiencing IPV from current male partners reported no abuse in
      the past year. Twice as many participants reported needing to see a doctor for
      abuse-related injuries, but not seeing one (6.3%), as actually seeing a doctor
      (3.1%). Only 11.3% of women reporting IPV reported having received any counseling
      related to the abuse. Other variables assessed were not related to abuse in
      current relationships. CONCLUSION: Domestic violence is a serious and highly
      prevalent concern among this group of South Asian women. Their knowledge of
      available services is limited, and victim-blaming attitudes are not uncommon.
      Culturally tailored domestic violence services and IPV education are needed for
      this underserved population.

PMID- 11991420
TI  - Discussing breast cancer risk in primary care.
AB  - Options for managing breast cancer risk now include screening, genetic testing,
      lifestyle modification, medication, and surgery. A woman's knowledge of her risk
      factors for breast cancer, her perceptions of that risk, and her concerns about
      cancer all shape her decisions about cancer screening and prevention. Physicians
      should involve women patients in making informed screening decisions, while
      reviewing their health risks and the benefits and risks associated with different
      courses of action. All women should be involved in this process, with special
      attention to older socioeconomically disadvantaged women, who are frequently left
      out of such discussions. Physicians can play a major role in reducing cancer
      disparities and the corresponding rates of breast cancer morbidity and mortality
      by keeping current in their knowledge of risk assessment, broadening the range of
      patients with whom they communicate about risk, and enhancing their communication
      skills to address diverse patient needs.

PMID- 11991421
TI  - A public health approach to the needs of children affected by terrorism.
AB  - The devastating terrorist incidents of Pan Am Flight 103, the Oklahoma City
      bombing, the bombings of the embassies in Kenya and Tanzania, and the World Trade
      Center attack of September 11, 2001, have forever changed America. These
      terrorist acts have deeply shaken the sense of safety, security, and well-being
      of our surviving children and families. These terrorist acts may also have
      increased the public health risks of substance abuse and mental illness for our
      children. The Substance Abuse and Mental Health Services Administration is
      responsible for strengthening prevention and treatment of substance abuse and
      mental illness in children and families. America's children may exhibit a wide
      range of emotional, physical, and psychological reactions following natural and
      man-made disasters. Large-scale disasters witnessed by children all underscore
      the need for a broad mental health and substance abuse public health approach.
      This approach is critical for our children's well-being.

PMID- 11991422
TI  - Research on advantages of "medical" versus "surgical" abortion.

PMID- 11991423
TI  - Improving palliative care: the need for change.

PMID- 11991424
TI  - Migraine and women's health.
AB  - Migraine is a significant women's health concern. Epidemiological research has
      demonstrated that migraine is one of the most common pain conditions and that
      women are disproportionately affected. Recent advances in pathophysiology
      highlight the hormonal antecedents of these sex differences in migraine and the
      potential influence of hormones on migraine pain pathways. Migraine spawns
      substantial suffering and disability and gives rise to great economic and
      personal burden. Despite the availability of effective pharmacological and
      nonpharmacological treatments, only a fraction of migraine sufferers receive
      state-of-the-art treatment. Access to effective treatment is limited by economic
      and social barriers to care, including the long-standing social stigma that
      trivializes headache. Although doubtless a women's health issue, migraine has
      been largely overlooked in the women's health initiatives. This paper argues that
      migraine is an important women's health concern and that greater attention to
      migraine promises to make a demonstrable improvement in the quality of life of
      many women.

PMID- 11991425
TI  - Why do men and women respond differently to chest pain? A qualitative study.
AB  - OBJECTIVES: to explore sex differences in responses to chest pain. METHOD:
      Qualitative interviews were conducted with 30 men and 30 women with chest pain,
      age 45 to 64, living in two socioeconomically divergent areas of Glasgow,
      Scotland. RESULTS: Three themes underpinned sex differences in responses to chest
      pain: perceived vulnerability to heart disease, previous experience of health
      care, and nonmedical care strategies. Men were perceived to be at greater risk of
      heart disease. Women were concerned that reporting their chest pain wasted the
      doctors' time. Men and women were equally likely to discuss their pain with lay
      others, but women were less likely to be directed to medical care. CONCLUSIONS:
      Despite initiatives to raise awareness that heart disease is important for women,
      women and their lay consultants continue to underestimate the significance of
      chest pain. Women's reluctance to seek medical care may contribute to sex
      differences in use of cardiology services.

PMID- 11991426
TI  - Hospice utilization by male and female cancer patients in an end-of-life
      transition program.
AB  - OBJECTIVE: to determine if there were sex differences in patients' use of hospice
      services in a regional cancer center in Texas from 1998 to 2000. METHODS: A
      quality-of-life program for patients with cancer that included an end-of-life
      component was initiated in 1998 at a regional cancer center. The records of 1057
      female and 986 male cancer patients who died from 1998 to 2000 were reviewed.
      Data on demographics, use of hospice care, length of stay, and location at time
      of referral were collected and analyzed. RESULTS: Hospice utilization increased
      in women (47% v 64%; p<.001) and men (53% v 66%; p<.001) who died of cancer from
      1998 to 2000. Length of stay (LOS) in hospice did not change for women, but
      decreased significantly for men over that time (31 days v 14 days, p<.001). The
      number of men with stays of 14 days or less increased significantly (30% v 53%,
      p<.001). Subjects whose LOS were less than 14 days were more likely to be
      hospital inpatients at time of referral. CONCLUSIONS: The institution of a
      targeted end-of-life program was associated with increased utilization of hospice
      services in women with cancer at this regional cancer center. Length of stay in
      hospice was longer for women than men, and more men had very short (less than 14
      day) stays. Hospice referrals from outpatient settings were associated with
      longer LOS.

PMID- 11991427
TI  - Benign breast pain in women: a practical approach to evaluation and treatment.
AB  - The literature on breast pain etiology, practical approaches to evaluating benign
      breast pain, and effective treatments was reviewed. Medline, the Cochrane
      Database of Systematic Reviews, and Cancerlit were searched for 1975 to 2001.
      Researchers have found no clear hormonal or specific pathological processes that
      explain cyclical breast pain. Some investigations did find associations between
      breast pain and premenstrual syndrome, fibrocystic breast disease, and caffeine
      intake. Initial treatment with reassurance, a well-fitted brassiere, caffeine
      reduction, and primrose oil should be tried before prescribing pharmaceutical
      agents. Medications such as danazol, bromocriptine, and tamoxifen are effective,
      but often have side effects and contraindications. Future studies should indude
      double-blind, randomized, controlled trials of selective-serotonin reuptake
      inhibitors and primrose oil and single-blind, randomized, controlled trials
      advising caffeine reduction.

PMID- 11991428
TI  - Gender, anxiety, and experimental pain sensitivity: an overview.
AB  - Our objective was to review human experimental studies to see if anxiety had a
      differential impact on the pain perceptions of men and women. We searched MEDLINE
      and PsycINFO for studies of anxiety and pain sensitivity in men and women
      published from 1966 to 2001. Research indicated that women are more sensitive to
      pain than men, and that anxiety may be partly responsible for the observed
      differences. Anxiety may also differentially affect men's and women's report of
      pain. Anxiety may be an important factor when considering sex differences in pain
      perception and warrants further investigation.

PMID- 11991429
TI  - Management of grief and loss: medicine's obligation and challenge.
AB  - One of medicine's least taught and acknowledged areas is the physicians'
      obligation to the surviving families of patients who have died under our care.
      The uncomfortable feelings engendered by the death of a patient often lead to
      ending contact with the family of the deceased. However, this response fails to
      recognize the importance of the role that the treating physician continues to
      have for the surviving family. A phone call, letter, or attendance at the funeral
      has enormous meaning and value for the family. This role also provides the doctor
      with an opportunity to deal with the "minigrief" reaction that follows the death
      of a special patient, and it reduces the adverse effects of unacknowledged,
      cumulative losses that lead to burnout. Although the deaths of patients and our
      efforts to help their grieving relatives may be the "dark" side of medicine, this
      side can be among the most rewarding when it helps bereaved loved ones and
      ourselves to survive loss.

PMID- 11991430
TI  - Chronic pain in later life women: issues and challenges from the research
      literature.
AB  - Because research on chronic pain in older adults comes from many disciplines,
      existing information about geriatric pain is widely scattered. In order to
      establish a foundation from which to construct future research and interventions
      for older women and men, we developed a comprehensive, multidisciplinary database
      of the chronic pain and aging literature published between 1990 and 1998. We
      searched 10 electronic databases that index scientific journals and found 302
      articles that focused on chronic pain in later life. Given the disproportionately
      high number of women in many of the study samples, gender comparisons were not
      always statistically feasible. Because a limited number of studies reported sex
      differences in older adults, it is difficult to determine whether older women's
      experiences with chronic pain are unique and require special attention from
      health care providers or whether the causes, treatments, and consequences of
      chronic pain should be considered universal to the older-population as a whole.

PMID- 11991431
TI  - The changing position of women in the medical marketplace: women's health morphs
      into gender-specific medicine.
AB  - Traditionally, society--including the academic medical community--has
      concentrated on the male patient. Women were protected from clinical
      investigation on human subjects. However, World War II brought about far-reaching
      changes. The experience of Americans during the prolonged struggle gave them an
      enduring confidence in the power of science to prolong and improve human life
      that culminated in the expansion of the National Institutes of Health under the
      leadership of James A. Shannon. The other profound change in American society was
      in the attitude of women, who, as a result of their enormously increased options
      during the war to hold jobs and enter professions that had previously been the
      exclusive province of men, united in the feminist movement. By the end of the
      1980s, the voices of women themselves galvanized the United States government to
      effect a series of maneuvers that have revolutionized our concept of the
      importance of biological sex in human biology. This paper reviews the changes in
      American medical research, and the delivery of medical care, to men and women
      over the past century, which laid the foundation for an in-depth exploration of
      the impact of gender on normal human function and the way human beings experience
      disease.

PMID- 11991432
TI  - The new conundrum: do estrogens have any cardiovascular benefits?
AB  - Clearly, a new era has begun, with increasing numbers of the scientific/medical
      community asking whether estrogens have any cardiovascular benefits. Doubts have
      arisen from two randomized prospective trials. The Heart and Estrogen/progestin
      Replacement Study (women who were generally beyond 65 years of age with
      preexisting coronary heart disease) found no benefit in reducing coronary events
      by a combination of estrogens and a progestin. Later, the Estrogen Replacement
      Atherosclerosis Trial reported that no benefit could be shown for either
      conjugated equine estrogens only or the combined therapy group for women with
      preexisting coronary artery stenosis. There are lessons to be taken from monkey
      models about the new conundrum. Estrogens have beneficial effects in the early
      stages of atherogenesis, but have little or no beneficial effects in the final
      stages of plaque complications, instability and coronary heart disease events.
      Using the monkey model, we have addressed the question of when "primary
      prevention" should begin. We examined the effect of contraceptive steroid
      treatment of stressed animals at high risk to progressing atherosclerosis due to
      their estrogen deficiency and subsequently examined the effect of estrogen
      replacement therapy or no estrogen replacement therapy following surgical
      menopause. The most robust inhibition of atherosclerosis progression was found in
      those animals given contraceptive steroids premenopausally and subsequently
      estrogen replacement postmenopausally. The notion of starting contraceptive
      therapy during the perimenopausal period to be followed immediately with estrogen
      replacement postmenopausally is likely to be the most favorable approach to the
      inhibition of atherosclerosis progression.

PMID- 11991433
TI  - The transdermal contraceptive patch: a new approach to hormonal contraception.
AB  - The transdermal contraceptive patch delivers ethinyl estradiol and norelgestromin
      (17-deacetylnorgestimate) at a rate over seven days that results in efficacy
      paralleling that achieved with oral contraceptives. Due to the pharmacokinetics
      of the system, adequate steroid levels are maintained for two days beyond the
      recommended duration of use of an individual patch, with resulting maintenance of
      efficacy. With perfect use, the failure rate is 0.70 pregnancies per 100 woman
      years and for typical use, the rate is 0.88 pregnancies per 100 woman-years. Body
      weight above 90 kilograms (198 pounds) is associated with lower efficacy. Cycle
      control is similar to that achieved by oral contraceptives. With the exception of
      a transient increase in breast tenderness, the side effect profile is similar to
      that noted by oral contraceptive users. A major advantage of this method compared
      to oral contraceptives is a nearly 90% perfect adherence to the dosing schedule
      across all age groups. Partial or total detachment of the patch occurs at an
      overall rate of 3.8%. This rate is not affected by warm humid climates, vigorous
      exercise, or exposure to saunas or water baths.

PMID- 11991434
TI  - Testosterone deficiency in women: etiologies, diagnosis, and emerging treatments.
AB  - Healthy young women produce approximately 300 microg of testosterone per day, of
      which about half is derived from the ovaries and half from the adrenal glands. In
      women, as in men, testosterone is thought to influence pubertal development,
      sexual function, bone density, muscle mass, erythropoiesis, energy, cognitive
      function and mood. Testosterone deficiency in women may result from a variety of
      conditions, including oophorectomy, adrenalectomy, adrenal disease, pituitary
      disease, HIV infection, premature ovarian failure, Turner's syndrome, and the use
      of high-dose corticosteroids and some estrogen preparations. Simple aging and
      natural menopause may also contribute to testosterone deficiency in some women. A
      consensus view of the diagnosis of female androgen deficiency syndrome (FADS) is
      currently being developed, and is summarized in this article, as are current
      approaches for treating testosterone deficiency in women. Recent clinical trials
      involving an experimental testosterone transdermal patch for women are
      highlighted. The impact of conventional ERT/HRT on testosterone levels in
      naturally menopausal women is discussed, with the differences between oral and
      transdermal routes of estrogen delivery being emphasized.

PMID- 11991435
TI  - Compelling reasons for recommending IUDs to any woman of reproductive age.
AB  - The intrauterine device (IUD) is a highly effective method of contraception that,
      as opposed to other countries around the world, is underutilized in the United
      States by women of all ages. Lingering concerns about the safety of IUDs are in
      large part responsible for their lack of adoption, but a systematic review
      published recently nullified some of the major safety concerns about IUD use. The
      author summarized the methodologically sound evidence regarding the risk of upper
      genital-tract infection and infertility associated with IUD use and reported that
      a slightly increased risk of pelvic inflammatory disease (PID) exists only in the
      first month following IUD insertion; that the risk of PID in women with
      symptomless sexually transmitted diseases (STDs) having an IUD inserted is
      similar to the risk in women not having an IUD inserted; and that there appears
      to be no negative effect on fertility following IUD removal. In addition, Mirena
      provides noncontraceptive benefits, such as treatment for menorrhagia,
      dysmenorrhea, and anemia, and ParaGard may help protect against endometrial
      cancer. An IUD is also a safer alternative to sterilization for perimenopausal
      women seeking a long-term and also reversible method of contraception. While both
      IUDs are suitable for many women of all ages, there are differences in their
      mechanisms of action, physical characteristics, and clinical effects that make
      each more or less appropriate for certain women.

PMID- 11991436
TI  - Vitamin D and muscle function.
AB  - The aim of this review is to summarize current knowledge on the relation between
      vitamin D and muscle function. Molecular mechanisms of vitamin D action on muscle
      tissue have been known for many years and include genomic and non-genomic
      effects. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D3
      (1,25(OH)2D) to its nuclear receptor, which results in changes in gene
      transcription of messenger RNA and subsequent protein synthesis. Non-genomic
      effects of vitamin D are rapid and mediated through a membrane-bound vitamin D
      receptor (VDR). Genetic variations in the VDR and the importance of VDR
      polymorphisms in the development of osteoporosis are still a matter of
      controversy and debate. Most recently, VDR polymorphisms have been described to
      affect muscle function. The skin has an enormous capacity for vitamin D
      production and supplies the body with 80-100% of its requirements of vitamin D.
      Age, latitude, time of day, season of the year and pigmentation can dramatically
      affect the production of vitamin D in the skin. Hypovitaminosis D is a common
      feature in elderly people living in northern latitudes and skin coverage has been
      established as an important factor leading to vitamin D deficiency. A serum 25
      hydroxyvitamin D level below 50 nmol/l has been associated with increased body
      sway and a level below 30 nmol/l with decreased muscle strength. Changes in gait,
      difficulties in rising from a chair, inability to ascend stairs and diffuse
      muscle pain are the main clinical symptoms in osteomalacic myopathy. Calcium and
      vitamin D supplements together might improve neuromuscular function in elderly
      persons who are deficient in calcium and vitamin D. Thus 800 IU of
      cholecalciferol in combination with mg of elemental calcium reduces hip fractures
      and other non-vertebral fractures and should generally be recommended in
      individuals who are deficient in calcium and vitamin D. Given the strong
      interdependency of vitamin D deficiency, low serum calcium and high levels of
      parathyroid hormone, however, it is difficult to identify exact mechanisms of
      action.

PMID- 11991437
TI  - Treatment of male osteoporosis: recent advances with alendronate.
AB  - Overall, the data from the two alendronate studies clearly document the efficacy
      and safety of alendronate in osteoporotic men. The positive effects of
      alendronate on BMD, markers and fractures are very consistent between studies.
      Importantly, they are also very consistent with the results of multiple clinical
      studies conducted in postmenopausal women with osteoporosis. Treatment with 10 mg
      alendronate for 2 years produced significant and clinically meaningful increases
      in BMD, similar to those previously observed in postmenopausal women. Data from
      studies including men and women confirm the similarity of response suggested by
      single-gender studies. Consistent with much larger studies in postmenopausal
      women, alendronate 10 mg/day also reduced the incidence of new vertebral fracture
      and, correspondingly, reduced height loss. The safety and tolerability of
      alendronate in men was favorable and consistent with the safety profile
      previously observed in postmenopausal women. Alendronate represents an important
      and needed therapeutic advancement in the management of osteoporosis in men.

PMID- 11991438
TI  - Soy product intake and serum isoflavonoid and estradiol concentrations in
      relation to bone mineral density in postmenopausal Japanese women.
AB  - To evaluate soy intake and serum concentrations of estradiol and isoflavonoids
      and their relationship to bone mineral density (BMD) and serum bone-specific
      alkaline phosphatase (bone ALP) activity, we conducted a cross-sectional study of
      87 postmenopausal Japanese women. Soy product and isoflavone intake from soy
      products and intake of nutrients were assessed with a semiquantitative food
      frequency questionnaire. BMD (mg/cm2) was measured by single-energy X-ray
      absorptiometry at the site of the calcaneus. Serum estradiol (E2) and the sex
      hormone-binding globulin (SHBG) were measured by radioimmunoassay. Serum
      genistein and daidzein concentrations were measured by a high-performance liquid
      chromatography MS/MS method. A statistically significant correlation was observed
      between the ratio of E2 to SHBG and BMD (Spearman r=0.38, p=0.0003) after
      controlling for age, body mass index, smoking status, age at menarche, and intake
      of vegetable fat, vitamin C and salt. Soy product and isoflavone intake and serum
      isoflavones were not significantly correlated with BMD after controlling for the
      covariates. Serum ALP was not significantly correlated with soy product and
      isoflavone intake, the E2/SHBG ratio or serum isoflavones. The present study
      supports the association of BMD with serum estradiol; however, it does not
      support the association of BMD with soy or isoflavone intake or serum isoflavone
      levels.

PMID- 11991439
TI  - Evaluation of osteoporosis treatment in seniors after hip fracture.
AB  - A retrospective chart review was carried out on all consecutive patients over 65
      years of age admitted to a tertiary care teaching hospital with a diagnosis of a
      new hip fracture. A further chart review occurred after discharge from post
      surgery rehabilitation. The primary objective was to evaluate the prevalence of
      osteoporosis diagnosis and treatment in both phases of the study. Secondary
      objectives included evaluation of the mortality rates, length of stay, prevalence
      of osteoporosis investigation, and prevalence of osteoporosis diagnosis based on
      the clinical subspecialty involved. There were 311 patients evaluated in the
      initial phase, and 226 after rehabilitation. The mortality rate was 5.8% (10% for
      men, 4% for women; p<0.005) in the acute care hospital and 9.3% (8% men, 10%
      women) during rehabilitation. Previous hip fracture occurred in 17.4%, and 1.5%
      were readmitted during the study period with fracture of the opposite hip.
      Osteoporosis was diagnosed in the acute care hospital on admission in 11.9% and
      on discharge in 15.4%. In the rehabilitation hospital it was diagnosed in 9.7% on
      admission and 11.2% on discharge (p=NS). Osteoporosis treatment (including
      calcium or vitamin D therapy) was instituted in 13% on admission to acute care
      and in 9.7% at the time of discharge. For the rehabilitation hospital, treatment
      occurred in 12.8% on admission and 10.2% on discharge. The diagnosis of
      osteoporosis significantly increased the prevalence of treatment (p<0.001). Use
      of specific agents (hormone replacement therapy, bisphosphonates or calcitonin)
      occurred in <66% of all patients. Osteoporosis is under-diagnosed and under
      treated in this group of elderly hip fracture patients. It is associated with
      significant mortality and morbidity and every effort should be made to prevent
      future fractures. Physicians in the 'front line' of hip fracture treatment are
      missing this key aspect of management in their patients. Education of these
      physicians, as well as the public, may be the key to addressing this care gap.

PMID- 11991440
TI  - Association of physical activity and calcium intake with the maintenance of bone
      mass in premenopausal women.
AB  - Altogether 92 initially 25- to 30-year-old women of 132 original subjects
      participated in this 4-year follow-up study, which evaluated the influence of
      physical activity and calcium intake on the bone mineral content (BMC) of
      premenopausal women. The subjects were originally selected for a cross-sectional
      study according to their level of physical activity (high PA+ and low PA-) and
      calcium intake (high Ca+ and low Ca-), and the original groups were maintained in
      this follow-up study. The mean loss of BMC (95% CI) in the pooled data was 1.5%
      (0.7% to 2.4%) at the femoral neck, 0.6% (-0.8% to 1.9%) at the trochanter and
      6.0% (4.5% to 7.4%) at the distal radius during the 4-year follow-up. According
      to repeated measures analyses of covariance neither physical activity nor
      physical fitness at baseline was associated with the rate of bone loss from the
      proximal femur. High calcium intake and the maintenance of body weight were both
      associated with a lower rate of bone loss from the proximal femur and distal
      radius. In addition, a long duration of breast feeding was associated with a
      higher rate of bone loss from the distal radius.

PMID- 11991441
TI  - Vitamin D receptor start codon polymorphism (Fok I) and bone mineral density in
      Chinese men and women.
AB  - The relationship between Fok I polymorphism of the vitamin D receptor start
      codon, bone mineral density (BMD) and vertebral fractures was studied in 684
      Chinese men and women. A significant trend was observed only in Chinese women
      aged 70-79 years. The mean BMD at the total body was 0.85 +/- 0.01 g/cm2, 0.82 +/
      0.01 g/cm2 and 0.84 +/- 0.01 g/cm2 for elderly women of the FF, Ff and ff
      genotypes respectively (p = 0.06 by ANOVA). Similar but statistically non
      significant trends were observed at the hip and spine. However, no association
      between BMD and the Fok I genotype was observed in younger women (aged 50-59
      years) and elderly men (aged 70-79 years). In all study groups, there was no
      effect of an interaction between Fok I polymorphism and calcium intake on BMD (p
      > 0.05 for the interaction effects by two-way ANOVA). No significant association
      was observed between Fok I polymorphism and vertebral fracture in elderly men or
      women (p > 0.05 by the chi-square test). We conclude that the Fok I polymorphism
      may have a weak effect on the BMD of elderly Chinese women.

PMID- 11991442
TI  - Graphic trace analysis of ultrasound at the phalanges may differentiate between
      subjects with primary hyperparathyroidism and with osteoporosis: a pilot study.
AB  - Bone loss characterizes both primary hyperparathyroidism (PHPT) and osteoporosis
      (OP) but with a different histologic pattern, and this could partially explain
      the different fracture incidence in these two populations. Quantitative
      ultrasound (QUS), influenced by bone structural parameters other than bone
      mineral density (BMD), could evidence these differences, opening new perspectives
      in the evaluation of patients with metabolic bone diseases. The aim of the
      present study was to investigate the usefulness of QUS graphic trace parameters,
      assessed at the phalanx, in discriminating between PHPT bone disease and
      osteoporosis. We studied 34 patients with PHPT (mean age 59.7 +/- 12.7 years), 35
      patients with OP (mean age 60.6 +/- 7.1 years) and 34 healthy subjects as
      controls (mean age 59.1+/- 9.4 years). In all subjects QUS measurements were
      performed at the phalanx with a Bone Profiler (IGEA, Italy), obtaining the
      amplitude-dependent speed of sound (AD-SoS), fast wave amplitude (FWA), signal
      dynamic (SDy), bone transmission time (BTT) and ultrasound bone profile index
      (UBPI). Moreover, serum calcium, phosphorus, parathyroid hormone (PTH), bone
      isoenzyme of alkaline phosphatase (B-ALP) and ionized calcium were measured in
      all subjects in the morning under fasting conditions. In PHPT patients BTT was
      correlated with PTH, ionized calcium and B-ALP levels (r = -0.47, -0.57 and 
      0.44, respectively; p < 0.01), whereas FWA, SDy and UBPI correlated only with B
      ALP (r = -0.43, -0.46 and -0.50, respectively; p <0.01). Moreover, FWA, SDY and
      UBPI were significantly (p<0.01) lower and BTT significantly (p<0.001) higher in
      OP than in PHPT patients. UBPI, BTT, FWA and the BTT/FWA ratio, but not SDy, were
      able to discriminate between the two groups (area under the curve =0.66, 0.69,
      0.67 and 0.81, respectively). Our findings show that ultrasound signal parameters
      are differently influenced by bone changes characterizing primary
      hyperparathyroidism or osteoporosis. This suggests that the QUS signal could be a
      useful instrument in discriminating and studying some of the bone alterations
      typical of metabolic bone diseases.

PMID- 11991443
TI  - Women's willingness to pay out-of-pocket for drug treatment for osteoporosis
      before and after the enactment of regulations providing public funding: evidence
      from a natural experiment in Israel.
AB  - This study examines women's willingness to pay (WTP) for drug treatment for
      osteoporosis before and after the enactment of regulations approving public
      funding for the drugs and for a hypothetical more effective but not funded drug.
      One hundred and nine postmenopausal women recruited sequentially from a large
      bone metabolism outpatient clinic in central Israel were asked by telephone
      interview to report their maximum WTP out-of-pocket for a drug that would reduce
      the risk of hip fracture by 50% in four hypothetical cases varying by the level
      of risk described. Additionally, after the regulations, responses were elicited
      also for a hypothetical more effective drug. Information regarding participants'
      sociodemographic and health characteristics, as well as their knowledge of
      osteoporosis, was also collected. Women would pay considerable sums of money
      (between 85% to 124% of the price of the drugs) for osteoporosis treatment and
      these sums increase significantly as the risk of suffering a hip fracture
      increases. After the enactment of the regulations, women were still willing to
      pay 54% to 100% of the price of the drugs out-of-pocket. Increased WTP after the
      regulations was associated with increased ability to pay and to lower levels of
      knowledge of the disease. After the enactment, participants' WTP for a more
      effective drug was no different from their WTP for a less effective drug. WTP
      measures show relative stability over time. The dissemination of information
      regarding policy or regulatory changes should be encouraged in order to ensure
      rational decision-making processes.

PMID- 11991444
TI  - Expression of steroid-converting enzymes in osteoblasts derived from rat
      vertebrae.
AB  - Studies in vitro and in vivo have shown that glucocorticoids and sex steroids
      play an important role in bone physiology and pathophysiology. In this study we
      investigated glucocorticoid and sex steroid conversion in osteoblasts derived
      from lumbar vertebrae of adult male and female rats. Progesterone was converted
      to inactive 20alpha-OH-progesterone and the conversion at day 5 was 16-fold
      greater than that at day 13 in both sexes (male/ female, 2.7/1.7 and 0.16/0.10
      nM/10(5)cells/24 h, respectively). The conversion of inactive androstenedione to
      active androgen testosterone in males and females was 1.2- and 2.4-fold greater
      at day 5 than at day 13, respectively (male/female, 0.40/0.70 and 0.34/0.30 nM/
      10 cells/24 h, respectively). These results suggest that osteoblasts possess
      20alpha-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD and that their
      activities are dependent on the stage of cell differentiation. At day 5,
      dehydroepiandrosterone was converted to androstenedione (male/female, 0.25/0.098
      nM/10(5)cells/24 h), to 7alpha-OH-dehydroepiandrosterone (male/female, 0.49/0.39
      nM/10(5)cells/24 h) and to 5-androstene-3beta,17beta-diol (male/female, 0.18/0.37
      nM/10(5)cells/24 h), indicating the presence of 3beta-HSD, 7alpha-hydroxylase and
      17beta-HSD, respectively. Both 3beta-HSD and 7alpha-hydroxylase activities
      declined with cell differentiation. Hormonally inactive cortisone was converted
      to active cortisol (male/female, 0.34/0.29 microM/10(6)cells/6 h) while
      conversion of cortisol to cortisone was not detectable, suggesting the presence
      of oxoreductase activity of 11beta-HSD-1. These results show, for the first time,
      the presence of 7alpha-hydroxylase and 20alpha-HSD in osteoblasts, and provide
      further evidence that osteoblasts metabolize a variety of steroid hormones and
      can thus regulate tissue responsiveness to them.

PMID- 11991445
TI  - Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol
      and norethindrone acetate in preventing postmenopausal bone loss.
AB  - In this 2-year, randomized study, we compared the efficacy and tolerability of
      tibolone 2.5 mg (n = 75), tibolone 1.25 mg (n = 76) and estradiol 2 mg plus
      norethindrone acetate 1 mg (E2/NETA: n = 74) for preventing bone loss in
      postmenopausal women. Bone mineral density (BMD), measured by dual-energy X-ray
      absorptiometry, and bone remodeling markers were assessed every 6 months. Side
      effects were assessed quarterly. After 24 months, the mean increase (+/- SD) in
      lumbar spine BMD from baseline was 3.6% +/- 2.9%, 1.9% +/- 3.5% and 6.8% +/- 4.5%
      in the tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA groups, respectively. All
      pairwise differences were significant. The proportion of responders (women with a
      change from baseline in lumbar spine BMD of > or = -2% after 2 years) was 95.7%,
      89.0% and 98.5% with tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA, respectively.
      Similar results were obtained for femoral BMD, although the difference between
      tibolone 2.5 mg and E2/NETA was not significant at 24 months. Decreases in bone
      remodeling markers were similar in the three groups. Vaginal bleeding was more
      common in the E2/ NETA group (33.8%) than with tibolone 2.5 mg (12.0%) or
      tibolone 1.25 mg (9.2%), as was breast pain (23.0%, 2.7% and 2.6%, respectively).
      Each treatment effectively prevented bone loss. Overall, tolerability of tibolone
      was better than with E2/NETA, because of less frequent vaginal bleeding and
      breast pain. This may promote long-term adherence.

PMID- 11991446
TI  - Use of phalangeal bone mineral density and multi-site speed of sound conduction
      to monitor therapy with alendronate in postmenopausal women.
AB  - In women with postmenopausal osteoporosis (PMO), response to therapy with
      bisphosphonates is conventionally monitored using central-site (hip and spine)
      bone mineral density (BMD), but more convenient alternatives are desirable.
      During a randomized parallel-group study of the efficacy of once-weekly (80 mg vs
      160 mg) oral alendronate in the treatment of PMO, 81 women (mean age 70.2 years
      +/- 4.6 SD) had BMD measurements of total hip (TH) and lumbar spine (LS) (L1-L4,
      Hologic); and of the middle phalanx of the middle digit of the non-dominant hand
      (accuDXA) at baseline and after 6 and 12 months of therapy with alendronate. At
      the same timepoints, subjects also had measurements of speed of sound (SOS)
      through bone at four sites (distal 1/3 radius, proximal phalanx of the third
      finger, midshaft of the tibia and fifth metatarsal) using the Sunlight Omnisense
      Ultrasound Bone Sonometer. Data from both patient groups were pooled for this
      analysis. Mean TH BMD at baseline was 0.705 g/cm2 +/- 0.093 (SD) and increased by
      1.7% +/- 2.3% and 2.5% +/- 2.3% at 6 and 12 months respectively (p = 0.09 and
      p<0.0001). Mean LS BMD at baseline was 0.718 +/- 0.076 g/cm2 and increased by
      3.9% +/- 3.6% and 6.1% +/- 3.5% at 6 and 12 months respectively (both p<0.0001).
      There was no statistically significant change from baseline in mean BMD by
      accuDXA at either 6 or 12 months. The only statistically significant changes in
      SOS were at the radius (decrease in SOS at 12 months, p= 0.04) and tibia
      (increase at 6 months, p<0.01, but no change between baseline and 12 months).
      Baseline correlation coefficients between accuDXA and LS and TH DXA were 0.22 (p
      = 0.05) and 0.27 (p = 0.02) respectively. Correlation coefficients between SOS
      and LS DXA ranged from 0.05 to 0.22; and between SOS and TH DXA ranged from -0.08
      to 0.10 (all p = NS). These data suggest that the response to alendronate therapy
      over this time period cannot be measured by accuDXA or Sunlight SOS at the sites
      studied.

PMID- 11991447
TI  - Combined calcium and vitamin D3 supplementation in elderly women: confirmation of
      reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II
      study.
AB  - Vitamin D insufficiency and low calcium intake contribute to increase parathyroid
      function and bone fragility in elderly people. Calcium and vitamin D supplements
      can reverse secondary hyperparathyroidism thus preventing hip fractures, as
      proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double
      masked, placebo-controlled confirmatory study. The intention-to-treat population
      consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD =
      7.1) randomized to the calcium-vitamin D3 fixed combination group (n = 199); the
      calcium plus vitamin D3 separate combination group (n = 190) and the placebo
      group (n = 194). Fixed and separate combination groups received the same daily
      amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar
      pharmacodynamic effects. Both types of calcium-vitamin D3 regimens increased
      serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a
      similar extent, with levels returning within the normal range after 6 months. In
      a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in
      the placebo group (mean = -2.36% per year, SD = 4.92), while remaining unchanged
      in women treated with calcium-vitamin D3 (mean = 0.29% per year, SD = 8.63). The
      difference between the two groups was 2.65% (95% CI = -0.44, 5.75%) with a trend
      in favor of the active treatment group. No significant difference between groups
      was found for changes in distal radius BMD and quantitative ultrasonic parameters
      at the os calcis. The relative risk (RR) of HF in the placebo group compared with
      the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to
      that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in
      agreement with those of Decalyos I and indicate that calcium and vitamin D3 in
      combination reverse senile secondary hyperparathyroidism and reduce both hip bone
      loss and the risk of hip fracture in elderly institutionalized women.

PMID- 11991448
TI  - Discrimination of proximal hip fracture by quantitative ultrasound measurement at
      the radius.

PMID- 11991449
TI  - Trabecular and cortical bone in the assessment of vertebral fracture risk.

PMID- 11991450
TI  - The skeptical browser. Some thoughts on universal information access.

PMID- 11991451
TI  - Trade journals.

PMID- 11991452
TI  - Oral cancer education.

PMID- 11991453
TI  - Elderly patient care.

PMID- 11991454
TI  - Intra-arterial injections.

PMID- 11991455
TI  - Access for children.

PMID- 11991456
TI  - More about access.

PMID- 11991457
TI  - Question of the month. Do you now or have you ever participated in a study club?

PMID- 11991458
TI  - Stealth advertising on the Internet: scumware.

PMID- 11991459
TI  - Curing-light intensity and depth of cure of resin-based composites tested
      according to international standards.
AB  - BACKGROUND: Several factors control the light curing of a resin-based composite:
      the composition of the composite, the shade of the composite, the wavelength and
      bandwidth of the curing light, the distance of the light from the composite, the
      intensity of the curing light and the irradiation time. The authors investigated
      the depth of cure of several shades of five brands of resin-based composites when
      irradiated via light in the 400- to 515-nanometer wavelength bandwidth at the
      International Organization for Standardization, or ISO, recommended intensity of
      300 milliwatts per square centimeter. The resin-based composites were irradiated
      for the times recommended by the products' manufacturers. METHODS: The authors
      used a curing light adjusted to emit 300 mW/cm2 in the 400-nm to 515-nm
      wavelength bandwidth to polymerize five samples of each composite brand type and
      shade. They measured depth of cure using a scraping method described in the ISO
      standard for resin-based composites. Depth of cure was defined as 50 percent of
      the length of the composite specimen after uncured material was removed by manual
      scraping. The authors determined a mean from the five samples of each composite
      brand and shade. RESULTS: Thirteen (62 percent) of 21 composite materials met the
      ISO standard depth-of-cure requirement of 1.5 millimeters. Six of the eight
      remaining materials met the depth-of-cure requirement when the authors doubled
      the irradiation time recommended by the product manufacturers. CONCLUSIONS AND
      CLINICAL IMPLICATIONS: Curing lights with an intensity of 300 mW/cm2 appear to
      effectively cure most resin-based composite materials when appropriate curing
      times are used, which, in some cases, are longer than those recommended by the
      manufacturers. Dentists should verify the depth of cure of a composite material
      as a baseline measure, and then check depth of cure periodically to confirm light
      and material performance. The ISO depth-of-cure measurement method can be used
      for this purpose.

PMID- 11991460
TI  - How xylitol-containing products affect cariogenic bacteria.
AB  - BACKGROUND: The authors examined the effect of xylitol, a naturally occurring
      sweetener, on levels of Streptococcus mutans and S. sobrinus. They also
      investigated xylitol's mechanism of action. METHODS: The authors compared
      cariogenic bacteria levels before and after exposure to xylitol products in
      children and adults. In the first study, 187 children received xylitol-containing
      snacks in school for four weeks. In the second study, two adults received xylitol
      candy for four weeks. Unstimulated saliva samples were taken from all subjects.
      Gingival samples also were taken from the adults. The authors plated the samples
      on selective microbiological media. Individual isolates were plated on media with
      varying concentrations of xylitol, and were identified using specific DNA probes.
      Genetic relatedness was determined via pulse-field gel electrophoresis. RESULTS:
      The children's salivary S. mutans levels remained stable before and after xylitol
      exposure. Further analysis of the S. mutans isolates was conducted for seven
      children. Bacteria from five of these children grew with 10 percent or less
      xylitol at baseline, while the bacteria from all seven children grew with 15
      percent xylitol after exposure to the xylitol-containing snacks, suggesting that
      the S. mutans increased in tolerance to xylitol during exposure. Six children had
      isolates with the same genotype at both time points. S. mutans and S. sobrinus
      levels were reduced in one of the adults as a result of xylitol exposure, and the
      bacterial isolates became more xylitol tolerant. In the second adult, S. mutans
      and S. sobrinus levels increased, while the subject maintained the same
      proportion of susceptible and tolerant strains as that at baseline. CONCLUSIONS:
      Overall, consumption of xylitol-containing snacks and candy did not reduce S.
      mutans levels. However, bacteria from five children and one adult became more
      xylitol tolerant. CLINICAL IMPLICATIONS: These results provide a basis on which
      xylitol-containing products can be recommended and xylitol's mechanism of action
      can be explained to patients.

PMID- 11991461
TI  - Comparing methods for diagnosing temporomandibular joint disk displacement
      without reduction.
AB  - BACKGROUND: Research is needed to assess the validity of the Clinical Diagnostic
      Criteria for Temporomandibular Disorders, or CDC/TMD. The authors conducted a
      prospective, double-blind study to determine whether applying the specific
      CDC/TMD diagnosis of TMJ internal derangement, or ID, type III would demonstrate
      good agreement with diagnoses obtained by MRI. METHODS: The study comprised 138
      TMJs in 69 subjects who had a clinical diagnosis of unilateral TMJ ID type III
      (disk displacement without reduction). The authors obtained bilateral sagittal
      and coronal MRIs to establish the corresponding diagnosis of disk-condyle
      relationship. RESULTS: For the CDC/TMD interpretations, the positive predictive
      value of ID type III for disk displacement without reduction was 86 percent, and
      for the presence of an ID it was 91 percent. The overall diagnostic agreement for
      ID type III was 78.3 percent with a corresponding K value of 0.57. Most of the
      disagreement was due to false-positive interpretations of an absence of ID.
      CONCLUSIONS: The results suggest that using CDC/TMD for ID type III is predictive
      for the presence of an ID but is not sufficiently reliable for determining disk
      displacement without reduction. Parameters other than the functional disk-condyle
      relationship may need to be addressed to account for the biological plausibility
      of this entity. CLINICAL IMPLICATIONS: A clinical TMJ-related diagnosis of ID
      type III may need to be supplemented by evidence from an MRI to determine the
      functional disk-condyle relationship. Investigation of longitudinal evidence,
      including risk factors, history and response to treatment, appears to be
      warranted.

PMID- 11991462
TI  - Clinical utility of a genetic susceptibility test for severe chronic
      periodontitis: a critical evaluation.
AB  - BACKGROUND: A genetic susceptibility test for severe chronic periodontitis is now
      commercially available. It detects the simultaneous presence of a specific form
      of two interleukin genes--allele 2 at the IL1A+4845 and IL1B+3954 loci. Patients
      are referred to as being "genotype-positive" if both of these alleles are
      present. A fundamental premise of the test is that a combination of these alleles
      is responsible for increased secretion of IL-beta, which results in a
      hyperinflammatory response to a bacterial challenge, thereby predisposing a
      person to develop severe chronic periodontitis. TYPES OF STUDIES REVIEWED: The
      authors reviewed controlled clinical trials that assessed the association between
      specific genotypes and the patient's susceptibility to increased bleeding on
      probing, periodontitis and loss of teeth or dental implants. RESULTS: The
      relationship between specific IL-1 genotypes and the level of IL-1beta in the
      gingival crevicular fluid is unclear. Similarly, the ability of the genetic
      susceptibility test to forecast which patients will develop increased bleeding on
      probing, periodontitis, or loss of teeth or dental implants is ambiguous.
      CLINICAL IMPLICATIONS: Additional prospective clinical trials are needed to
      determine the risk of developing periodontitis or peri-implantitis when allele 2
      at the IL1A+4845 and IL1B+3954 loci is present. Therefore, it is unclear how
      results of the genetic susceptibility test can be used to alter patients'
      periodontal maintenance schedules or to change treatment regimens in
      periodontally symptomatic or asymptomatic patients.

PMID- 11991463
TI  - The integrity of bonded amalgam restorations: a clinical evaluation after five
      years.
AB  - BACKGROUND: Bonded amalgam restorations have been studied extensively in vitro,
      but few long term clinical studies exist. The authors examined the clinical
      performance of bonded amalgam restorations after five years of clinical service
      an compared it with that of nonbonded amalgam restorations. METHODS: The authors
      placed 75 bonded and 62 nonbonded amalgam restorations in patients needing
      restorations. Most of the restorations were placed in conventional preparations;
      six bonded restorations were placed in nonretentive cavities. They were evaluated
      after a five-year period of clinical service by two trained dentists using a
      mirror and explorer and following modified U.S. Public Health Service criteria.
      RESULTS: Statistical analysis (via Fisher exact test) showed no significant
      differences between the two techniques when conventional preparations were used.
      Restorations in nonretentive preparations were successful during this period.
      CONCLUSIONS: Bonded and nonbonded amalgam restorations yielded similar results in
      conventional preparations after five years of clinical service. Bonded amalgam
      restorations were clinically successful in a limited number of nonretentive
      preparations over a five-year period. CLINICAL IMPLICATIONS: Bonded amalgam
      restorations can be used successfully in conventional preparations and possibly
      in nonretentive preparations as well, and can be expected to last at least five
      years.

PMID- 11991464
TI  - Circulatory dynamics during dental extractions in normal, cardiac and transplant
      patients.
AB  - BACKGROUND: The authors conducted a study to evaluate the relationship between
      the circulatory dynamics of patients with heart disease and these patients'
      cardiac status when undergoing dental extractions. METHODS: Subjects with minimal
      heart disease, or MHD; with severe heart disease, or SHD; or who received a heart
      transplant, or TRAN; as well as control, or NOR, subjects were enrolled in the
      study. The authors recorded subjects' systolic blood pressure, or SBP; diastolic
      blood pressure, or DBP; and heart rate, or HR, while they were under basal
      conditions and during postanesthesia and dental extraction periods. The authors
      estimated a general linear model and performed analysis of variance. RESULTS:
      Under basal conditions, MHD subjects did not show significantly different mean
      blood pressure values compared with NOR subjects but did show slightly
      significantly higher mean HR values. Mean DBP and HR values were significantly
      higher in SHD and TRAN subjects than in MHD and NOR subjects, while SBP values in
      SHD subjects were significantly lower than those in MHD, TRAN and NOR subjects.
      During dental extraction sessions, SBP, DBP and HR mean values increased
      significantly compared with basal conditions and post-anesthesia periods in MHD
      and NOR subjects. SHD and TRAN subjects showed no significant time-dependent
      variation during dental extraction sessions in any circulatory parameter.
      CONCLUSIONS: MHD subjects had cardiovascular responses to stress similar to those
      of NOR subjects, while SHD and TRAN subjects had similar slight and dulled
      cardiac responses. CLINICAL IMPLICATIONS: Patients with SHD may not be able to
      adapt their cardiac performance to an emotional stress such as a dental
      appointment, while it seems to be easier for MHD and TRAN patients. Managing TRAN
      patients is relatively easier than managing SHD patients.

PMID- 11991465
TI  - Using a Hedstrom endodontic file to retrieve a root tip.

PMID- 11991466
TI  - The funding of dental services among U.S. children 2 to 17 years old: recent
      trends in expenditures and sources of funding.
AB  - BACKGROUND: This article is the first of two that focus on recent changes in the
      funding of dental services in the United States. METHODS: This study is based on
      analyses of data regarding dental expenditures among children 2 to 17 years of
      age from the 1987 National Medical Expenditure Survey and the 1996 Medical
      Expenditure Panel Survey. Both of these surveys were designed to produce national
      estimates of annual medical expenditures in the United States. RESULTS: Overall,
      real per capita dental expenditures among 2- to 17-year-old children who had had
      a dental visit fell from $578.05 in 1987 to $498.57 in 1996. Large increases per
      patient were reported for the poorest children, while decreases were reported for
      children from families with higher incomes. CONCLUSIONS: Much of the increase
      from 1987 to 1996 in dental expenditures among economically disadvantaged
      children who had had a dental visit was due to an increase in care provided by
      dentists that was not reimbursed. PRACTICE IMPLICATIONS: More needs to be done to
      increase the number of economically disadvantaged children who visit a dentist.
      All segments of society must cooperate to achieve this result.

PMID- 11991467
TI  - Electronic monitoring of dental implant osseointegration.
AB  - BACKGROUND: The methods for evaluating dental implant osseointegration can be
      limited in their effectiveness. The authors developed a new noninvasive
      electronic instrument to test implant stability and improve the assessment
      process. METHODS: Using the new instrument, which was based on impulse testing
      and fast Fourier transform, or FFT, technology, the authors tested implant
      stability under real-time clinical conditions. The clinical procedure involved a
      weekly test of two placed implants, from the first-stage insertion point to the
      completion of the integration. This longitudinal monitoring spanned eight months.
      RESULTS: The authors verified clinical implant integration electronically and
      that it closely matched mathematical predictions. They also observed changes in
      implant stability during the integration process. CONCLUSIONS: Implant stability
      can be monitored electronically using FFT testing. A theoretical integration
      prediction also can be formulated. Like a "dental electrocardiogram," integration
      is assessed by waveform shape analysis. CLINICAL IMPLICATIONS: Electronic
      measurement of implant stability may help clinicians noninvasively diagnose the
      suitability of implants for restoration and aid in postrestorative monitoring.

PMID- 11991468
TI  - Refund please: an ethical view--and a real-life application of the ADA code.
      American Dental Association.

PMID- 11991469
TI  - The perception of professionalism in dentistry: further reflections on a lively
      topic.
AB  - The dental profession has had a long period of unselfish service to the public.
      The professional reputation of dentists has been excellent. It appears to many
      dentists and patients that the profession's reputation has been tarnished by the
      perceived move toward profit over service.

PMID- 11991470
TI  - Topical fluoride for office use.

PMID- 11991471
TI  - Topical fluoride.

PMID- 11991472
TI  - For the dental patient: Diet and tooth decay.

PMID- 11991473
TI  - Tranquility base.

PMID- 11991474
TI  - Shockwave therapy for chronic proximal plantar fasciitis: a meta-analysis.
AB  - PURPOSE: Utilizing meta-analysis, the authors have reviewed the available
      literature to assess the biologic and therapeutic effects of shockwaves on
      patients with chronic plantar fasciitis and the credibility of these published
      studies. METHODS: Meta-analysis is a systematic method for statistical analysis
      that combines data from various independent studies, allowing the assessment of
      potential benefits of various treatments when conclusions based on individual
      studies may be difficult to evaluate. We hypothesized that extracorporeal
      shockwave therapy provided a reasonable nonoperative therapeutic alternative to
      surgical intervention in the treatment of chronic proximal plantar fasciitis.
      RESULTS: Eight of 20 published studies fulfilled our type A to C criteria for
      acceptable studies of sufficient duration (one year or more after treatment).
      These eight studies involved 840 patients, with success rates of as much as 88%.
      The other 12 studies had methodological variables or lack of appropriate follow
      up data that would limit their validity, although the success rates were
      comparable to the A to C studies. CONCLUSIONS: This meta-analysis shows that the
      directed application of shockwaves to the enthesis of the plantar fascia at the
      inferior calcaneus is a safe and effective nonsurgical method for treating
      chronic, recalcitrant heel pain syndrome that has been refractory to other
      commonly used nonoperative therapies. The results suggest that this therapeutic
      procedure should be considered before any surgical intervention, and may be
      preferable prior to cortisone injection, which has a recognized risk of rupture
      of the plantar fascia and a frequent recurrence of symptoms.

PMID- 11991475
TI  - Extracorporeal shockwave therapy (ESWT) in patients with chronic proximal plantar
      fasciitis.
AB  - The aim of this study was to compare the effect of extracorporeal shockwave
      therapy (ESWT) in patients with chronically painful proximal plantar fasciitis
      with a conventional conservative treatment consisting of nonsteroidal anti
      inflammatory drugs, heel cup, orthoses and/or shoe modifications, local steroid
      injections and electrotherapy. Forty-seven patients (49 feet) with a previously
      unsuccessful conservative treatment of at least six months were randomized to two
      groups. Treatment of Group 1 (25 heels) started immediately with three sessions
      of ESWT (3000 shockwaves/session of 0.2 mJ/mm2) at weekly intervals. In the
      patients of Group 2 (24 heels) treatment was continued for 12 weeks. After this
      period they were treated using the protocol of Group 1. No significant difference
      of pain and walking time after further non-ESWT treatment (three months) was
      seen. Six months after ESWT pain decreased by 64% to 88% on the visual analog
      scale (VAS) and the comfortable walking time had increased significantly in both
      groups.

PMID- 11991476
TI  - The functional outcome of displaced intra-articular calcaneal fractures: a
      comparison between isolated cases and polytrauma patients.
AB  - This study was conducted to analyze the functional outcome of displaced intra
      articular calcaneal fractures in polytrauma patients and isolated cases, and to
      make a comparison between them. Twenty-eight patients (12 women and 16 men) with
      an average age of 37 (range, 13 to 60) who had 35 displaced intra-articular
      calcaneal fractures were included in this study. Among these, 17 fractures were
      due to polytrauma and 18 were due to isolated trauma. According to Sanders CT
      classification, 19 fractures (54.3%) were classified as type II, 10 fractures
      (28.5%) as type III and six fractures (17.2%) as type IV. The treatment consisted
      of operative and closed methods. The average follow-up time was 38 months (range,
      18 to 83 months). The functional outcome was evaluated using Maryland Foot Score
      and there were three (17%) excellent, nine (52.9%) good and five (29.5%) fair
      results in polytrauma patients Seven (38.8%) excellent, 10 (55.6%) good and one
      (5.6%) fair results were seen in isolated cases. When compared with isolated
      cases, the functional outcome of displaced intra-articular calcaneal fractures in
      polytrauma patients was worse. With the findings available, it appears that foot
      trauma is usually ignored and should be treated without delay as for other system
      injuries in polytrauma patients.

PMID- 11991477
TI  - Extensile exposure of the subtalar joint.

PMID- 11991478
TI  - Keller procedure and chevron osteotomy in hallux valgus: five-year results of
      different surgical philosophies in comparable collectives.
AB  - We evaluated 97 Keller procedures and 64 chevron osteotomies, both combined with
      the "Cerclage fibreux" distal soft-tissue procedure, with a minimum follow-up
      period of five years to assess the limits of indications of these two different
      operations. We then formed two subgroups providing a statistical midrange of the
      metatarsophalangeal angle, intermetatarsal angle I-II and degree of arthrosis of
      the first metatarsophalangeal joint to obtain comparable collectives of 40 Keller
      and 36 chevron procedures. The postoperative AOFAS score averaged 85.4 for the
      Keller procedure and 83.0 for chevron patients. The metatarsophalangeal angle was
      improved to an average of 11.0 degress and 13.9 degrees, the intermetatarsal
      angle to values of 8.8 degrees and 9.4 degrees, respectively. The patient's
      overall satisfaction rated "very satisfied" and "satisfied" in 92.5% and 94.4%,
      respectively. The main reason for dissatisfaction was pain. Compared to the
      literature, the good long-term results in this series following resection
      arthroplasty are attributed to the routine use of the "Cerclage fibreux"
      technique. This contemporary type of the Keller procedure is still a valuable
      surgical procedure for older patients with minor functional expectations.
      Excellent outcome after chevron osteotomy was not only seen in younger patients
      with minor deformities, but also in an older population. The chevron osteotomy
      should not be restricted to younger patients. The combination of the chevron
      distal metatarsal osteotomy with a distal soft-tissue procedure does not increase
      the risk of clinically manifest avascular necrosis of the metatarsal head and
      helps to correct higher metatarsophalangeal and intermetatarsal angles.

PMID- 11991479
TI  - Total contact casting: its effect on contralateral plantar foot pressure.
AB  - Total contact casts (TCC) are commonly used in the treatment of neuropathic
      ulcers of the foot related to diabetes. However, casts may alter the gait pattern
      and increase loading parameters of the contralateral foot. We determined the
      effects of total contact casting on plantar pressure parameters for the
      contralateral extremity. Ten healthy subjects consented to walk, for four
      consecutive trials, along a 25-meter corridor while wearing a running shoe (RS),
      fiberglass TCC and a traditional TCC. Parameters of peak pressure, contact time
      and pressure-time integrals for the contralateral forefoot, metatarsal V area and
      heel were recorded using the novel Pedar system of plantar pressure measurement.
      Repeated measures analyses of variance (footwear x region) were used to analyze
      the recorded parameters with post-hoc Tukeys selected for follow-up analysis.
      Each of the measured parameters for the forefoot, lateral foot over metatarsal V
      and heel regions on the contralateral foot were similar regardless of footwear
      worn. Use of a TCC does not appear to affect contralateral foot contact pressure
      parameters and likely does not increase the risk of contralateral ulceration.

PMID- 11991480
TI  - Patellar tendon-bearing, patten-bottom caliper suspension orthosis in active
      Charcot arthropathy: crutch-free ambulation with no weight bearing in the foot.
AB  - A custom, patellar-tendon bearing (PTB), patten-bottom, caliper suspension
      orthosis was constructed for six patients with severe, active (Eichenholtz stage
      I) Charcot arthropathy of the ankle and hindfoot. With the orthosis, the
      suspended foot and ankle remained completely non-weight-bearing, and the lower
      extremity supported full weight bearing along the posterior and anterior leg
      shells and PTB crest. Four of the six patients used the orthosis to ambulate
      without crutches, leaving the upper extremities free for functional use. Frequent
      adjustment of the orthosis and skin examination were required. Minor problems
      with the orthosis included superficial skin breakdown and downward pistoning of
      the leg associated with improper, loose donning. Patient compliance was poor in
      four of the six patients because of general debility, difficulty with balance,
      and discomfort. However, in the other two patients, the absence of mechanical
      forces on the foot and ankle in the orthosis allowed the swelling and erythema of
      the active phase of Charcot arthropathy to resolve within several weeks, with
      maintenance of functional ambulation during the months required for healing of
      the Charcot process.

PMID- 11991481
TI  - Functional outcome of multiply injured patients with associated foot injury.
AB  - Fourteen polytrauma patients with foot injuries were compared to 14 polytrauma
      patients without foot injury in this review. The patients were selected from our
      institution's trauma registry. Criteria for selection included a minimum Injury
      Severity Score of 12 and a minimum follow-up of 12 months. The AAOS lower limb
      and foot and ankle outcomes data collection questionnaires were used to evaluate
      a patient's perception of the results. Marked differences were noted in the
      patients' physical function (80.7 vs. 38.9), role physical (87.5 vs. 41.1),
      bodily pain (81.9 vs. 50.6), social function (96.6 vs. 67.9), physical health and
      pain (83.3 vs. 43.5), satisfaction with symptoms (4.0 vs. 1.5), global foot and
      ankle (100 vs. 57.6), and shoe comfort scores (100 vs. 18.9) in foot injured vs.
      control patients, respectively. Although it is intuitively obvious that a patient
      with a foot injury vs. one without a foot injury who has suffered polytrauma may
      have a worse outcome, the profound differences in the above scores draw attention
      to the importance of the proper management of patients with musculoskeletal
      injuries who survive polytrauma injuries.

PMID- 11991482
TI  - Cavus foot correction in adults by dorsal closing wedge osteotomy.
AB  - Twelve patients (13 feet) who underwent dorsal closing wedge osteotomy for cavus
      foot deformity were re-examined clinically and radiographically 46 months after
      surgery (range, 24 to 80 months). A dorsally based bone wedge, sized according to
      the deformity on the preoperative radiographs, was excised between the Lisfranc
      and Chopart joint lines. Eight patients (nine feet) were satisfied with the
      procedure. Although significant improvement of both symptoms and foot alignment
      was achieved, most patients continued to experience mild to moderate pain
      postoperatively. The outcome seems not to be directly related to the achieved
      surgical correction.

PMID- 11991483
TI  - Symptomatic bipartite medial cuneiform in an adult athlete: a case report.
AB  - We present the case of a 32-year-old female marathon runner with a symptomatic
      bipartite medial cuneiform. The bipartite articulation was best visualized on a
      30 degress external oblique radiograph of the foot. Surgical exploration revealed
      a noncartilaginous articulation between the two osseous segments. The smaller
      medial segment was excised. Postoperatively the patient's symptoms resolved, and
      at one-year follow-up she remains asymptomatic and has returned to competitive
      running. This case demonstrates that surgical excision is indicated for a
      symptomatic bipartite medial cuneiform that fails to respond to nonoperative
      measures.

PMID- 11991484
TI  - Peg-in-socket arthrodesis of the first metatarsophalangeal joint.

PMID- 11991485
TI  - Interference screw fixation of tendontransfers in the foot and ankle.

PMID- 11991486
TI  - The rovibrational Hamiltonian for ammonia-like molecules.
AB  - A new exact quantum mechanical rovibrational Hamiltonian operator for ammonia
      like molecules is derived. The Hamiltonian is constructed in a molecular system
      of axes, such that its z' axis makes a trisection of the pyramidal angle formed
      by three bond vectors with the vertex on the central atom. The introduced set of
      the internal rovibrational coordinates is adapted to facilitate a convenient
      description of the inversion motion. These internal coordinates and the molecular
      axis system have a remarkable property, namely, the internal vibrational angular
      momentum of the molecule equals zero. This property significantly reduces the
      Coriolis coupling and simplifies the form of the Hamiltonian. The correctness of
      this Hamiltonian is proved by a numerical procedure. The orthogonal Radau vectors
      allowing us to define a similar molecular axis system and the internal
      coordinates are considered. The Hamiltonian for the Radau parameterization takes
      a form simple enough to carry out effectively variational calculations of the
      molecular rovibrational states. Under the appropriate choice of the variational
      basis functions, the Hamiltonian matrix elements are fully factorizable and do
      not have any singularities. A convenient method of symmetrization of the basis
      functions is proposed.

PMID- 11991487
TI  - A realistic double many-body expansion potential energy surface for SO2(X1A')
      from a multiproperty fit to accurate ab initio energies and vibrational levels.
AB  - A single-valued double many-body expansion potential energy surface (DMBE I)
      recently obtained for the ground electronic state of the sulfur dioxide molecule
      by fitting correlated ab initio energies suitably corrected by scaling the
      dynamical correlation energy is now refined by fitting simultaneously available
      spectroscopic levels up to 6886 cm(-1) above the minimum. The topographical
      features of the novel potential energy surface (DMBE II) are examined in detail,
      and the method is emphasized as a robust route to fit together state-of-the-art
      theoretical calculations and spectroscopic measurements using a single fully
      dimensional potential form.

PMID- 11991488
TI  - One-dimensional quantum description of the bending vibrations of HCN/CNH for high
      values of the total angular momentum.
AB  - For high values of the quantum number of the total angular momentum J (up to J =
      20), quantum mechanical eigenstates (eigenvalues and eigenfunctions) are
      calculated by the method of Gatti et al. (J. Mol. Spectrosc. 181 (1997) 403) for
      the bending deformations of HCN and CNH. In particular, we have examined the l
      type resonances in highly excited rovibrational states within the framework of a
      one-dimensional model, i.e. along the reaction pathway for the isomerization
      reaction HCN/CNH. The potential energy surface used is that of Bowman et al. (J.
      Chem. Phys. 99 (1993) 308).

PMID- 11991489
TI  - Ab initio rotation-vibration energy levels of triatomics to spectroscopic
      accuracy.
AB  - The factors that need to be taken into account to achieve spectroscopic accuracy
      for triatomic molecules are considered focusing on H3+ and water as examples. The
      magnitude of the adiabatic and non-adiabatic corrections to the Born-Oppenheimer
      approximation is illustrated for both molecules, and methods of including them ab
      initio are discussed. Electronic relativistic effects are not important for H3+,
      but are for water for which the magnitude of the various effects is discussed.
      For H3+ inclusion of rotational non-adiabatic effects means that levels can be
      generated to an accuracy approaching 0.01 cm(-1); for water the error is still
      dominated by the error in the correlation energy in the electronic structure
      calculation. Prospects for improving this aspect of the calculation are
      discussed.

PMID- 11991490
TI  - Ab initio rotation-vibration spectra of HCN and HNC.
AB  - We have calculated an ab initio HCN/HNC linelist for all transitions up to J= 25
      and 18000 cm(-1) above the zero point energy. This linelist contains more than
      200 million lines each with frequencies and transition dipoles. The linelist has
      been calculated using our semi-global HCN/HNC VQZANO + PES and dipole moment
      surface, which were reported in van Mourik et al. (J. Chem. Phys. 115 (2001)
      3706). With this linelist we synthesise absorption spectra of HCN and HNC at 298
      K and we present the band centre and band transition dipoles for the bands which
      are major features in these spectra. Several of the HCN bands and many of the HNC
      bands have not been previously studied. Our line intensities reproduce via fully
      ab initio methods the unusual intensity structure of the HCN CN stretch
      fundamental (00(0)1) for the first time and also the forbidden (02(2)0) HCN
      bending overtone. We also compare the J = 1-->0 pure rotational transition dipole
      in the HCN/HNC ground and vibrationally excited states with experimental and
      existing ab initio results.

PMID- 11991491
TI  - First-principles rovibrational analysis of the H3+-molecule.
AB  - The fitting of highly accurate potential energy points and of the diagonal
      adiabatic coupling for H3+ using different functional forms is presented. A
      recently derived analytical potential based on 69 points has been extended to
      give a highly reliable form of the topology of the surface far beyond the barrier
      to linearity. Rovibrational frequencies have been derived and are compared with
      experiment. Detailed information about the experimentally observed rovibrational
      transitions near 1.25 microm will be given. The computed transition frequencies
      reproduce experimental transitions within a tenth up to a few hundredths of a
      wavenumber, if a simulation of non-adiabatic effects is taken into account.

PMID- 11991492
TI  - Quantum calculation of highly excited vibrational energy levels of CS2(X) on a
      new empirical potential energy surface and semiclassical analysis of 1:2 Fermi
      resonance.
AB  - We report a refined potential energy function for the ground electronic state of
      CS2 based on a least-squares fitting to several low-lying experimental
      vibrational frequencies. Energy levels up to 20,000 cm(-1) have been obtained on
      this empirical potential using the Lanczos algorithm and potential optimized
      discrete variable representation. Among them, 329 levels below 10,000 cm(-1) are
      assigned with approximate normal mode quantum numbers (n1, n(0)2, n3), based on
      expectation values of one-dimensional (1D) reference Hamiltonians. An effective
      Hamiltonian is extracted from these assigned levels. The agreement with
      experimental data, including those of several isotopically substituted species,
      is excellent. In addition, some Fermi and anharmonic resonances are analyzed. The
      nearest neighbor level spacing and delta3 distributions indicated that the
      vibrational spectrum of CS2 is largely regular in the energy range up to 20,000
      cm(-1). Semiclassical phase space analysis, including bifurcation analysis of the
      spectroscopic Hamiltonian, is used to interpret subtle anomalies signaled by
      expectation values used in normal mode assignments. The meaning of Fermi
      resonance is clarified by contrasting the semiclassical analysis of CS2 and CO2.

PMID- 11991493
TI  - Ab initio vibration and ro-vibrational spectrum of the 1A1 state of He2Si2+.
AB  - The low-lying ro-vibrational states for the ground electronic state (1A1) of
      HeSi2+ have been calculated using an ab initio variational solution of the
      nuclear Schrodinger equation. A 96 point CCSD(T)/cc-pCVQZ potential energy
      surface (PES) has been calculated and a Ogilvie-Pade (3,6) potential energy
      function has been generated. This force field was embedded in the Eckart-Watson
      Hamiltonian from which the vibrational and ro-vibrational eigenfunctions and
      eigenenergies have been variationally calculated. A 70 point QCISD/aug-cc-pCVTZ
      discrete dipole moment surface (DMS) was calculated and a 5th order power series
      expansion (in terms of the two bond lengths and the included bond angle) has been
      generated. Absolute line intensities have been calculated and are presented for
      some of the most intense transitions between the vibrational ground state and the
      low-lying ro-vibrational states of this ion.

PMID- 11991494
TI  - The Renner effect in triatomic molecules with application to CH+, MgNC and NH2.
AB  - We have developed a computational procedure, based on the variational method, for
      the calculation of the rovibronic energies of a triatomic molecule in an
      electronic state that become degenerate at the linear nuclear configuration. In
      such an electronic state the coupling caused by the electronic orbital angular
      momentum is very significant and it is called the Renner effect. We include it,
      and the effect of spin-orbit coupling, in our program. We have developed the
      procedure to the point where spectral line intensities can be calculated so that
      absorption and emission spectra can be simulated. In order to gain insight into
      the nature of the eigenfunctions, we have introduced and calculated the overall
      bending probability density function f(p) of the states. By projecting the
      eigenfunctions onto the Born-Oppenheimer basis, we have determined the
      probability density functions f+(rho) and f-(rho) associated with the individual
      Born-Oppenheimer states phi(-)elec and phi(+)elec. At a given temperature the
      Boltzmann averaged value of the f(p) over all the eigenstates gives the bending
      probability distribution function F(rho), and this can be related to the result
      of a Coulomb Explosion Imaging (CEI) experiment. We review our work and apply it
      to the molecules CH2+, MgNC and NH2, all of which are of astrophysical interest.

PMID- 11991495
TI  - Discrete variable approaches to tetratomic molecules: part I: DVR(6) and DVR(3) +
      DGB methods.
AB  - We present two discrete variable representation (DVR) based methods for the
      determination of the vibrational energy levels of tetratomic molecules. Both
      methods are designed for orthogonal internal coordinates in a body-fixed
      reference frame and make use of the DVR of three angular variables. The angular
      DVRs allow the construction of a fixed-angle three-mode Hamiltonian for the
      stretching vibrations. For each of the angular triples, the stretching eigenvalue
      problems are solved by employing 3D radial DVRs in the DVR(6) approach and real
      three-dimensional distributed Gaussian functions in the DVR(3) + DGB method. The
      angular degrees of freedom are taken sequentially into account in conjunction
      with a contraction scheme resulting from several diagonalization/truncation
      steps. Vibrationally averaged geometries, expectation values of rotational
      constants, and several adiabatic projection schemes developed in this work for
      tetratomic molecules are used to characterize the vibrational levels calculated
      by the DVR(6) and DVR(3) + DGB.

PMID- 11991496
TI  - Discrete variable approaches to tetratomic molecules: part II: application to
      H2O2 and H2CO.
AB  - We have carried out large-scale calculations for accurate vibrational energy
      levels of formaldehyde and hydrogen peroxide. The discrete variable
      representations of the radial and angular coordinates are employed together with
      the contraction scheme resulting from several diagonalization/truncation steps.
      The global potential energy surface due to Carter et al. [J. Mol. Spectrosc. 90
      (1997) 729] is used for H2CO and due to Koput et al. [J. Phys. Chem. A 102 (1998)
      6325] for H2O2. For both molecules, the calculated vibrational energy levels are
      characterized by combining vibrationally averaged geometries and expectation
      values of rotational constants with several adiabatic projection schemes for
      automatic quantum number assignments. The energy levels of H2CO involving the
      excited v2 and v3 vibrations appear as resonances beyond the zero-order picture
      consisting of uncoupled 3D stretching and 2D bending modes. The torsional energy
      levels of H2O2 are studied in great detail and different energy patterns
      occurring below and above the cis barrier are discussed. Our full dimensional
      calculations for H2O2 have shown that the OH triad levels, 2vOH, are symmetry
      adapted local mode states.

PMID- 11991497
TI  - The vibrational levels of ammonia.
AB  - A new six-dimensional potential energy function (PEF) of ammonia expressed in
      internal coordinates is determined by fitting to points evaluated by Density
      Functional Theory with the B97-1 functional. The C3v and D3h structures are
      treated on an equal footing. The inversion barrier is 1820 cm(-1), which is in
      very good agreement with the experimental value of 1834 cm(-1). The minimum
      'reaction path' is well defined by the analytic function up to 40 degrees for the
      umbrella angle. Using this PEF, the vibrational levels are calculated
      variationally using three different methods. The first employs the internal
      kinetic energy operator developed for ammonia by Handy, Carter and Colwell (Mol.
      Phys. 96 (1999) 477). The second uses the code MULTIMODE (J. Chem. Phys. 107
      (1997) 10458), which involves the kinetic energy operator as expressed in normal
      coordinates by Watson. The third uses an implementation of the reaction path
      hamiltonian (J. Chem. Phys. 72 (1980) 99) within the MULTIMODE code. All three
      approaches give similar energies for the vibrational energies of ammonia, and
      these agree with experiment to within 15 cm(-1) for the fundamental vibrations.

PMID- 11991498
TI  - Full dimensional calculations of vibrational energies of H3O+ and D3O+.
AB  - We report full dimensional calculations of vibrational energies of H3O+ and D3O+
      using two implementations of the code MULTIMODE. In one implementation, the
      reference geometry is the minimum of the potential (the standard choice for
      MULTIMODE). This implementation is not able to readily describe splittings in the
      vibrational energies due to motion through the inversion barrier. A second
      implementation, in which the reference geometry is the inversion saddle point, is
      able to describe the splittings. These full dimensional calculations are done
      using the realistic, though not spectroscopically accurate, potential of Ojamae,
      Singer and Shavitt, and the results are compared with experiment.

PMID- 11991499
TI  - Towards accurate ab initio predictions of the vibrational spectrum of methane.
AB  - We have carried out extensive ab initio calculations of the electronic structure
      of methane, and these results are used to compute vibrational energy levels. We
      include basis set extrapolations, core-valence correlation, relativistic effects,
      and Born-Oppenheimer breakdown terms in our calculations. Our ab initio
      predictions of the lowest lying levels are superb.

PMID- 11991500
TI  - The anharmonic potential energy surface of methyl fluoride.
AB  - A large experimental spectroscopic data set sensitive to the cubic anharmonic
      potential energy surface (PES) of methyl fluoride has been compiled from the
      literature for six symmetric and asymmetric top isotopomers of methyl fluoride:
      12CH3F, 13CH3FF, 12CD3F, 13CD3F, 12CHD2F and 12CH2DF. This empirical data set has
      been used to critically assess the best available literature ab initio cubic
      force field and various 'improved' theoretical force fields. A perturbation
      resonance approach to the calculation of the observables from the force constants
      has been utilized and existing PESs were found to reproduce the data poorly. The
      careful treatment required for the correct theoretical reproduction of empirical
      spectroscopic constants arising from highly correlated least-squares fits to the
      original data is discussed. A new fit to the data has been performed (optimising
      19 of the 38 cubic force constants) resulting in a much improved PES. The latter
      has been used to predict currently unknown spectroscopic constants for the least
      well-characterised isotopomer 12CH2DF. The prospects for a future empirical
      determination of the complete cubic force field of methyl fluoride are discussed
      and new data most likely to yield new information on the PES identified.

PMID- 11991501
TI  - Ab initio calculations of anharmonic vibrational spectroscopy for hydrogen
      fluoride (HF)n (n = 3, 4) and mixed hydrogen fluoride/water (HF)n(H2O)n (n = 1,
      2, 4) clusters.
AB  - Anharmonic vibrational frequencies and intensities are computed for hydrogen
      fluoride clusters (HF)n, with n = 3, 4 and mixed clusters of hydrogen fluoride
      with water (HF)n(H2O)n where n = 1, 2. For the (HF)4(H2O)4 complex, the
      vibrational spectra are calculated at the harmonic level, and anharmonic effects
      are estimated. Potential energy surfaces for these systems are obtained at the
      MP2/TZP level of electronic structure theory. Vibrational states are calculated
      from the potential surface points using the correlation-corrected vibrational
      self-consistent field method. The method accounts for the anharmonicities and
      couplings between all vibrational modes and provides fairly accurate anharmonic
      vibrational spectra that can be directly compared with experimental results
      without a need for empirical scaling. For (HF)n, good agreement is found with
      experimental data. This agreement shows that the Moller-Plesset (MP2) potential
      surfaces for these systems are reasonably reliable. The accuracy is best for the
      stiff intramolecular modes, which indicates the validity of MP2 in describing
      coupling between intramolecular and intermolecular degrees of freedom. For
      (HF)n(H2O)n experimental results are unavailable. The computed intramolecular
      frequencies show a strong dependence on cluster size. Intensity features are
      predicted for future experiments.

PMID- 11991502
TI  - Damage control surgery: an alternative approach for the management of critically
      injured patients.
AB  - Over the past 20 years, it has gradually become apparent that the results of
      prolonged and extensive surgical procedures performed on critically injured
      patients are often poor, even in experienced hands. The triad of hypothermia,
      coagulopathy, and metabolic acidosis effectively marks the limit of the patient's
      ability to cope with the physiological consequences of injury, and crossing this
      limit will frustrate even the most technically successful repair. These
      observations have led to the development of a new surgical strategy that
      sacrifices the completeness of immediate repair in order to adequately address
      the combined physiological impact of trauma and surgery. This approach is
      unfolded in three phases. During the initial operation, the surgeon carries out
      only the absolute minimum necessary to rapidly control exsanguination and prevent
      the spillage of intestinal contents and urine into the peritoneal cavity. Packing
      represents the traditional method for the management of major liver injuries. The
      second phase consists of secondary resuscitation in the intensive care unit,
      characterized by maximization of hemodynamics, correction of coagulopathy,
      rewarming, and complete ventilatory support. During the third phase, the intra
      abdominal packing is removed and definitive repair of abdominal injuries is
      performed. The "damage control" concept has been shown to increase overall
      survival and is likely to modify the management of the critically injured
      patient.

PMID- 11991503
TI  - Effects of modified ultrafiltration on coagulation factors in pediatric cardiac
      surgery.
AB  - PURPOSE: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in
      children has been reported to reduce the need for postoperative blood transfusion
      and minimize postoperative blood loss. This study was undertaken to quantify the
      effects of MUF on coagulation factors in pediatric patients. METHODS: Seven
      children scheduled to undergo open-heart surgery for congenital heart defects
      were studied. CPB circuits were primed with crystalloid solutions and no blood
      transfusions were performed. Hematocrit, platelet count, total plasma proteins,
      albumin, fibrinogen, prothrombin, factor VII, factor IX, and factor X were
      measured preoperatively, at the termination of cardiopulmonary bypass, and at the
      end of modified ultrafiltration. RESULTS: MUF was associated with significant (P
      < 0.05) increases in hematocrit (17.6% +/- 1.6% to 21.6% +/- 2.4%), platelet
      count 11.1 +/- 2.5 to 12.8 +/- 2.4 x 10(4)/mm3), total plasma proteins (2.7 +/-
      0.3 to 3.4 +/- 0.4 g/dl), and albumin (1.6 +/- 0.2 to 2.1 +/- 0.2 g/dl).
      Fibrinogen, prothrombin, and factor VII also increased significantly (P < 0.05)
      during MUF, but factor IX and factor X did not change. CONCLUSION: We conclude
      that MUF attenuates the dilutional coagulopathy that occurs during CPB in
      children. There were slight improvements in the coagulation factors when MUF was
      employed.

PMID- 11991504
TI  - Significance of the initial arterial lactate level and transpulmonary
      arteriovenous lactate difference after open-heart surgery.
AB  - PURPOSE: This study was conducted to determine the clinical significance of the
      initial lactate level and its transpulmonary difference after open-heart surgery
      in adult patients. METHODS: The initial postoperative lactate levels were
      obtained from both radial and pulmonary arteries (La, Lv) in 65 consecutive
      patients undergoing coronary (n = 46), valve (n = 8), and aortic (n = 11)
      surgery. We analyzed the relationships between the perioperative factors and La
      and transpulmonary arteriovenous lactate difference (%La-v = 100(La - Lv)/Lv).
      RESULTS: La and % La-v were not correlated with the preoperative factors of age,
      pulmonary function, or emergency surgery. La significantly correlated with the
      cardiopulmonary bypass time, initial arterial pH, initial PaO2/FiO2, SvO2, O2
      consumption, O2 extraction rate, and the peak value of creatine phosphokinase.
      The %La-v significantly correlated with the aortic cross-clamp time, the lowest
      rectal temperature, the duration of intubation, and PaO2/FiO2 after extubation.
      CONCLUSION: La may be an indicator of the invasiveness of the surgery, while %La
      v may be a predictor of postoperative pulmonary function. Both La and %La-v, as
      an initial value in the intensive care unit, may play an important role in
      planning the postoperative management of patients undergoing open-heart surgery.

PMID- 11991505
TI  - Quality of life after esophagectomy for cancer: an assessment using the
      questionnaire with the face scale.
AB  - PURPOSE: The face scale has not been used as a global parameter of quality of
      life (QOL). The aims of this study were to assess the QOL of patients after
      esophagectomy for cancer and to examine whether a face scale is useful as a
      global parameter of QOL. METHOD: Seventy-one patients without postoperative
      recurrence after curative esophagectomy answered the questionnaire with the face
      scale and food intake. We calculated the QOL score (its full mark: 85) and
      examined the correlation between the QOL score and other parameters including the
      face scale. RESULT: The duration of the postoperative period ranged from 8 to 253
      months (median 87 months). Gastric pullups at the left cervix were selected in 66
      patients. The retrosternal route was performed in 55 patients. The mean QOL score
      was 64.2 (range 33-84). There was the significant positive correlation between
      QOL score and the face scale (P < 0.0001). The quantity of meal intake decreased
      in 55 patients (77.55%) by more than 50% compared with their healthy state. About
      a half of the subjects still suffered from the swallowing problems and a
      decreased food intake. CONCLUSION: The face scale is correlative with the total
      QOL score after an esophagectomy and is useful as a global parameter of the QOL.

PMID- 11991506
TI  - Regular finger dilation for preventing anastomotic stenosis after low anterior
      resection.
AB  - PURPOSE: This study evaluated the usefulness of performing regular finger
      dilation (RFD) of the anastomosis to prevent stenosis after low anterior
      resection (LAR). METHODS: Defecatory function was assessed in 22 patients who had
      undergone LAR more than 6 months earlier. The patients were divided into an RFD
      group, comprising 15 patients who had undergone regular RFD, and a non-RFD group,
      comprising 7 patients who had dropped out of our follow-up with RFD. The
      physiological and clinical findings in relation to defecatory function were
      compared. RESULTS: The type and size of the stapler and anal manometric
      parameters were similar. The RFD group had significantly better defecatory
      function in terms of bowel movement and sensation of incomplete evacuation (P <
      0.01, respectively) with a significantly wider anastomotic diameter and higher
      evacuation rate (P < 0.01, respectively). CONCLUSION: These findings demonstrate
      that RFD is useful for preventing anastomotic stenosis and achieving favorable
      defecatory function after LAR. Therefore, a prospective randomized study should
      be scheduled.

PMID- 11991507
TI  - Surgical management of splenic hydatidosis.
AB  - PURPOSE: This study was conducted to evaluate the surgical management of splenic
      hydatidosis in an area where the disease is endemic. METHOD: Over a period of 16
      years, 26 patients with splenic hydatidosis underwent surgery in our department.
      Preoperative investigations included plain abdominal X-ray, serology,
      ultrasonography, and computed tomography. RESULTS: In our series, splenic
      hydatidosis represented 3.5% of total abdominal hydatidosis. The majority of
      patients presented with abdominal discomfort and palpable swelling in the left
      hypochondrium. Twenty-two patients were operated on electively and 4 as emergency
      cases, including 2 with ruptured hydatids and 2 with infected hydatids of the
      spleen. Isolated splenic hydatid cysts were present in 21 patients, associated
      liver hydatid cysts in 4, and diffuse abdominal hydatidosis in 1 patient. All
      patients underwent splenectomy except for one patient who initially had partial
      splenectomy for a lower polar cyst. This patient also ended up undergoing a
      splenectomy for postoperative hemorrhage. One patient died on the sixth
      postoperative day (mortality rate 3.8%) as a result of multiorgan failure, and 4
      developed minor complications (morbidity 15.4%). CONCLUSION: Splenic hydatidosis,
      although rare, is the third most common type of hydatidosis after liver and lung
      hydatidosis. This entity should thus be kept in mind when encountering a splenic
      cyst especially in areas where the disease is endemic. A splenectomy remains the
      treatment of choice because it demonstrates low morbidity and mortality rates.

PMID- 11991508
TI  - Effects of carvedilol alone and in the presence of cyclosporine A on the DNA
      synthesis of cultured vascular smooth muscle cells.
AB  - PURPOSE: There is still no reliable method of preventing or treating chronic
      rejection or transplant vascular sclerosis. A recent in vitro cell culture study
      showed that carvedilol significantly inhibited the proliferation of vascular
      smooth muscle cells (VSMCs); however, the effect of carvedilol in the presence of
      cyclosporine (CsA) has not yet been reported. Using in vitro cultured VSMCs, we
      measured the antiproliferative activity of carvedilol alone and in combination
      with CsA. METHODS: Growth-arrested cultured VSMCs from the thoracic aorta of
      Sprague-Dawley rats were exposed to platelet-derived growth factor (PDGF)-BB,
      endothelin (ET)-I, and angiotensin (ANG)-II. Carvedilol (1 and 10 microM) and/or
      CsA (100 nM) were added as test drugs. DNA synthesis was assessed by measuring
      the incorporated [3H]thymidine activity, and the percentage of inhibition in the
      presence of the test drugs was determined. RESULTS: Compared with the PDGF
      stimulated control, DNA synthesis decreased significantly to 60.3% +/- 10.4% and
      18.3% +/- 5.9% in the presence of 1 and 10 microM of carvedilol, respectively (P
      < 0.05, each). Carvedilol significantly inhibited the activity of VSMCs
      stimulated by ET-1 and ANG-II. The IC50 of carvedilol was 1-10 microM. CsA only
      inhibited VSMCs significantly in the PDGF-stimulated subgroup. The addition of
      CsA in the presence of carvedilol did not affect the inhibitory activity of
      carvedilol. The pattern of inhibition in the combined group was uniform and
      similar to that of the carvedilol alone group, regardless of the stimulator used.
      CONCLUSION: Carvedilol significantly inhibited the DNA synthesis of VSMCs
      regardless of the kind of stimulators examined, even in the presence of CsA.
      These results indicate that carvedilol has the unique potential to inhibit the
      development of transplant vascular sclerosis in hypertensive transplant
      recipients under CsA-based immunosuppression.

PMID- 11991509
TI  - Interleukin-12 administration is more effective for preventing metastasis than
      for inhibiting primary established tumors in a murine model of spontaneous
      hepatic metastasis.
AB  - PURPOSE: The effect of interleukin-12 (IL-12) on tumor growth at the primary site
      and its therapeutic efficacy against metastasis were examined using a model of
      spontaneous hepatic metastasis. METHODS: IL-12 was peritumorally injected into RL
      male1 tumor-bearing BALB/c male mice at the different tumor stage. RESULTS:
      Striking inhibition of hepatic metastasis in both athymic and euthymic mice was
      induced by the administration of IL-12 irrespective of the stage of tumor
      progression. In contrast, IL-12 failed to produce any antitumor effect in athymic
      mice which lack conventional T cells. These results suggest that the antitumor
      effect of IL-12 is mediated mainly by T cells, and that the antimetastatic effect
      is mediated mainly by natural killer (NK) and/or NKT cells. Next we examined the
      direct effect of IL-12 on these cells. IL-12-induced T-cell proliferation was
      remarkably augmented in the early stage, then decreased dramatically in the
      advanced stage, while IL-12-induced cytotoxic activity, mediated by NK and NKT
      cells, was not attenuated even in the advanced stage. This dissociation in IL-12
      responsiveness appeared to be the reason for the remarkable antimetastatic effect
      but insufficient antitumor effect of IL-12 in the advanced stage. CONCLUSION: The
      findings of this study support the clinical use of IL-12 for immunotherapy
      against either occult or evident liver metastasis.

PMID- 11991510
TI  - Revascularization to prevent postoperative bowel infarction after surgery for
      acute superior mesenteric artery thromboembolism.
AB  - PURPOSE: Postoperative bowel infarction is a major contributing factor to the
      high mortality rate associated with acute thromboembolism of the superior
      mesenteric artery (SMA). This study was conducted to evaluate the prophylactic
      role of thrombectomy to prevent postoperative mesenteric infarction. METHODS: An
      autologous fibrin clot (1 cm3) was implanted into the SMA of beagle dogs. The
      animals in group I (n = 7) underwent only resection of the ischemic intestine 120
      min after insertion of the thrombus. In group IIa (n = 6), the intestine was
      removed before thrombectomy of the SMA, and revascularization was performed 30
      min prior to resection in group IIb (n = 6). The postoperative outcomes were
      compared among the three groups. RESULTS: Postoperative bowel infarction
      developed in four (57.1%) of the group I dogs, three (42.8%) of which died within
      5 days postoperatively. The SMA was patent in the group IIa and IIb dogs, none of
      which died throughout the observation period. Performing thrombectomy before the
      resection reduced the length of resected intestine. CONCLUSION: Arterial
      revascularization is not only an essential procedure for mesenteric infarction
      due to SMA thromboembolism, but it also prevents the postoperative bowel
      infarction caused by the extension of thrombus in the mesentery.

PMID- 11991511
TI  - The inhibitory effect of octreotide on experimental colorectal carcinogenesis.
AB  - PURPOSE: This study was conducted to investigate the effect of octreotide on
      colorectal carcinogenesis by administering octreotide either alone or combined
      with polyglactin, which is a well-known suture material, on chemically induced
      colorectal cancer development in rats. METHODS: A total of 72 rats were divided
      into six groups. Two groups were subjected to a colotomy and repair using
      polyglactin. Another two groups underwent a sham procedure. The fifth group
      received octreotide alone and the sixth group served as a control. Both groups of
      rats in the polyglactin and sham groups received octreotide additionally.
      Methylnitrosourea was administered rectally to all the animals at a dose of 4
      mg/kg per week for 20 weeks to induce carcinogenesis. Octreotide was injected
      twice a day at a total daily dose of 100 microg/kg. The thymidine labeling index
      was used to assess the synthesis phase fraction in order to measure the cell
      proliferation rate. RESULTS: The mean number of tumors per rat was significantly
      higher in the polyglactin group than in both the sham and control groups. It was
      significantly lower in the octreotide and polyglactin + octreotide groups than in
      the control and polyglactin groups, respectively. All the animals in the
      octreotide group had one tumor, while 66.6% of the control group had multiple
      tumors. The number of multiple tumors was significantly lower in the polyglactin
      + octreotide and sham + octreotide groups than in the polyglactin and sham
      groups, respectively. The mean tumor size in the octreotide group was
      significantly smaller than in the control group, whereas it was larger in the
      polyglactin group in comparison with the sham and control groups. It was also
      reduced in the polyglactin + octreotide group in comparison with the polyglactin
      group. The thymidine labeling index was significantly higher in the polyglactin
      group compared with both the sham and control groups, whereas it was lower in the
      octreotide group in comparison with the control group. The addition of octreotide
      administration to the polyglactin usage and the sham procedure significantly
      decreased the thymidine labeling indexes. CONCLUSION: These results indicate that
      octreotide reduces the frequency of tumor occurrence and has an inhibitory effect
      on its development in chemically induced experimental colorectal cancer.
      Octreotide can also reduce the enhancing effect of polyglactin on colorectal
      carcinogenesis when it is combined with polyglactin.

PMID- 11991512
TI  - Invasive ductal carcinoma of the breast associated with Poland's syndrome: report
      of a case.
AB  - We report herein a rare case of invasive ductal carcinoma of the breast
      associated with Poland's syndrome. The patient was a 59-year-old woman who was
      referred to our department after a nodule had been found in the upper outer
      portion of the left breast by a breast cancer screening program. On physical
      examination, marked hypoplasia of the right breast and upper limb was noted.
      Preoperative computed tomography also revealed a defect in the right pectoralis
      muscles. A quadrantectomy of the left breast with lymphadenectomy was
      subsequently performed and pathological examination of the resected specimen
      showed invasive ductal carcinoma. Her medical history revealed that her mother
      had attempted to abort the pregnancy around the fifth week of her gestation. The
      present case suggests that such an event during gestational development may be
      associated with congenital anomalies predisposing to malignant disorders.

PMID- 11991513
TI  - Treatment of necrotic infection on the anterior chest wall secondary to
      mastectomy and postoperative radiotherapy by the application of omentum and mesh
      skin grafting: report of a case.
AB  - We report herein the case of a patient who initially underwent right radical
      mastectomy for breast carcinoma in 1988, followed by left breast-conserving
      surgery in 1997. On both occasions she was given postoperative radiation therapy
      of 50 Gy. Repeated dressings and the administration of antibiotics failed to heal
      ulcerative infected lesions that had formed on the anterior chest wall in early
      1998. In 1999, the sternum and surrounding tissue were debrided and the anterior
      chest wall was reconstructed by omentum transposition and mesh skin grafting. The
      patient is currently well and alive without any evidence of recurrence of either
      infection or breast cancer.

PMID- 11991514
TI  - Thymoma associated with hypogammaglobulinemia (Good's syndrome): report of a
      case.
AB  - A 63-year-old man was admitted to our hospital for treatment of
      hypogammaglobulinemia with thymoma (Good's syndrome). Tests for immunological
      function showed an abnormality in humoral immunity with decreases in the
      proportion of cells bearing B-cell markers in the peripheral blood and bone
      marrow. The patient was found to have Campylobacter fetus sepsis caused by the
      hypogammaglobulinemia due to humoral immunodeficiency, and he was given gamma
      globulin supplement. Thymectomy was performed due to enlargement of the thymoma
      after 4 years of follow-up and the pathological diagnosis was thymoma of the non
      encapsulated, epithelial spindle cell type. Although there was no recurrence of
      thymoma, the hypogammaglobulinemia remained unchanged and the patient continued
      to suffer from repeated infections. Thus, we describe the case of a patient with
      Good's syndrome associated with independent humoral immunodeficiency in whom the
      effect of thymectomy for hypogammaglobulinemia was negative. In this respect,
      thymectomy was only beneficial when the thymoma proliferated and seemed to be
      more threatening than the hypogammaglobulinemia for the patient.

PMID- 11991515
TI  - Spontaneous pneumothorax secondary to radiographically occult lung metastasis
      from parapharyngeal synovial sarcoma: report of a case.
AB  - This report describes a case of secondary pneumothorax caused by a
      radiographically occult lung metastasis from parapharyngeal synovial sarcoma, a
      relatively rare tumor known to be highly metastatic to the lung. Although chest X
      ray and thoracic computed tomography scan failed to detect the metastatic nodule
      in the right lung, the surgically resected specimen proved to be a 3-mm lung
      metastasis. To our knowledge, only eight cases of lung metastases from synovial
      sarcoma causing pneumothorax have ever been reported. In most of these cases, the
      lung metastases were detected by radiographical examinations. However, in this
      patient, the metastatic lesion was not detected during examination. It is
      speculated that secondary pneumothorax caused by synovial sarcoma may occur
      during the early stages of lung metastasis. Therefore, if pneumothorax occurs in
      a patient with a synovial sarcoma, the possibility of lung metastasis should be
      carefully considered, even if it is undetectable on radiological examinations.

PMID- 11991516
TI  - Surgical treatment of malignant fibrous histiocytoma in the left atrium and
      pulmonary veins: report of a case.
AB  - This report describes the case of a 16-year-old boy who underwent surgical
      treatment of a cardiac malignant fibrous histiocytoma (MFH). He was admitted to
      our hospital for exertional dyspnea. An ultracardiogram (UCG) revealed a tumor
      about 10cm in diameter, in the left atrium. Extirpation of the left atrial tumor,
      including the part extending into the pulmonary veins, was performed under
      cardiopulmonary bypass. Histological examination confirmed a diagnosis of MFH. No
      adjuvant chemotherapy or radiotherapy was given. While there has been no evidence
      of local recurrence or metastasis in the 9 months since his operation, strict
      follow-up is being done by UCG and computed tomography. A few reviews of this
      entity have been reported; however, they have confused autopsy cases with
      surgical cases. Therefore, we reviewed only the surgical cases of this type of
      cardiac tumor documented in the literature. According to our review of the
      literature, this patient is the youngest among the 42 cases of surgically treated
      cardiac MFH reported to date.

PMID- 11991517
TI  - Epithelioid hemangioendothelioma of the stomach: clinical-pathological features,
      nosologic setting, and surgical therapy. Report of a case.
AB  - Vascular tumors of the stomach represent 0.9%-3.3% of all gastric neoplasms. A 41
      year-old man was admitted to our department with a 3-month history of early
      postprandial epigastric pain, sluggish digestion, nausea, asthenia, and
      occasional alimentary emesis. Preoperative staging detected a submucosal
      neoformation in the prepyloric zone, which narrowed the lumen, without any
      infiltrative features; a wedge gastric resection was performed and the definitive
      diagnosis was an epithelioid hemangioendothelioma of stomach. An 8-month follow
      up did not show any relapse of the disease. The term hemangioendothelioma is
      controversial because of disagreements regarding the nosologic setting and
      treatment. As a result, the latest WHO classification calls such neoplasms
      "borderline." The correct diagnosis depends on the histological findings
      supported by immunohistochemistry. Surgery represents the treatment of choice;
      however, a conservative approach is preferred whenever possible. However, due to
      the borderline biological behavior of this neoplasm, it is important that
      detailed clinical evaluations be carried out for such patients along with a
      thorough follow-up.

PMID- 11991518
TI  - A hemophagocytic syndrome-like condition after emergency colectomy for perforated
      colon cancer: report of a case.
AB  - Hemophagocytic syndrome is a rare but often fatal condition, and little is known
      about why this disorder can occur following surgery. We report herein the case of
      a patient successfully treated for a hemophagocytic syndrome-like condition that
      developed after emergency right hemicolectomy for a retroperitoneal abscess
      secondary to perforated colon cancer. The 62-year-old man initially presented
      after the sudden development of severe right back pain, and computerized
      tomography scans revealed a retroperitoneal abscess continuous with a tumor in
      the ascending colon. An emergency right hemicolectomy was subsequently performed.
      On postoperative day (POD) 2, his blood platelet count suddenly dropped to 1 x
      10(4)/microl and histological examination of a bone marrow specimen taken on POD
      5 showed abnormal histiocytes that had phagocytosed not only megakaryocytes, but
      also erythrocytes and leukocytes, and a normocellular marrow with a normal number
      of megakaryocytes. Hemophagocytic syndrome was suspected, and predonine was
      administered. The patient's condition improved remarkably and he was discharged
      on POD 51.

PMID- 11991519
TI  - Diverticulitis causing a high serum level of carbohydrate antigen 19-9: report of
      a case.
AB  - We report herein a rare case of diverticulitis causing a high serum level of
      carbohydrate antigen (CA) 19-9. A 52-year-old man was admitted to our hospital
      with lower abdominal pain. Laboratory data showed evidence of inflammation and a
      high serum level of CA 19-9 (370 U/ml). Computed tomography demonstrated
      thickening of the wall of the sigmoid colon. He was diagnosed as having
      diverticulitis of the sigmoid colon and was treated with antibiotics. Although
      his symptoms improved, the presence of a malignancy such as colorectal cancer
      could not be completely ruled out because of the persistently high serum level of
      CA 19-9. A laparotomy was performed and the sigmoid colon was found to be
      adherent to the bladder. Under a diagnosis of diverticulitis, a sigmoidectomy was
      performed. Pathological examination revealed diverticulitis of the sigmoid colon,
      but there was no evidence of malignancy in the resected specimen. The serum CA 19
      9 level decreased to normal postoperatively and immunohistochemical staining
      revealed CA 19-9 antigen in the cytoplasm of the diverticular epithelium.
      Therefore, a possible explanation for the high level of this tumor marker was
      diverticulitis of the sigmoid colon.

PMID- 11991520
TI  - Xanthogranulomatous cholecystitis with a liver abscess and metastatic
      endophthalmitis: report of a case.
AB  - There have been no reported cases of xanthogranulomatous cholecystitis with a
      liver abscess and metastatic endophthalmitis in the literature. There has been
      only one other case of xanthogranulomatous cholecystitis associated with a liver
      abscess in Japan prior to the present report. A 53-year-old man was admitted to a
      local hospital complaining of high fever. Abdominal ultrasonography and computed
      tomography showed a liver abscess. After percutaneous transhepatic abscess
      drainage, he complained of an abnormal sensation in his left eyeball and was
      diagnosed to have endophthalmitis. After being treated for the endophthalmitis,
      he was referred to our hospital to have the liver abscess evaluated. Endoscopic
      retrograde cholangiopancreatography showed a normal biliary system without any
      communication with the liver abscess. Two weeks after endoscopic retrograde
      cholangiopancreatography he complained of right hypochondralgia. Ultrasonography
      revealed the presence of sludge in the swollen gallbladder. Under a diagnosis of
      cholecystitis with a liver abscess, a cholecystectomy was performed. A
      histological examination indicated xanthogranulomatous cholecystitis based on the
      findings of a granulomatous lesion consisting of foamy cells in the gallbladder
      wall. We herein present the first known case of xanthogranulomatous cholecystitis
      with a liver abscess and metastatic endophthalmitis, while also making a review
      of the literature.

PMID- 11991521
TI  - A new abdominal drain insertion technique after a cirrhotic liver resection to
      prevent ascitic leakage.
AB  - A simple technique for inserting an abdominal drain is reported to prevent the
      leakage of ascitic fluid at the abdominal drainage site after a cirrhotic liver
      resection. This technique consists of inserting the abdominal drain through a
      subcutaneous tract. When the drain is then removed during the postoperative
      period, the pressure of the ascitic fluid that has built up in the peritoneal
      cavity causes pressure which thus obliterates the subcutaneous tract and thereby
      prevents leakage. This technique was found to be easy to perform, safe, and
      effective.

PMID- 11991522
TI  - Biological and chemical factors influencing shallow lake eutrophication: a long
      term study.
AB  - The focus of eutrophication research has tended to be upon short-term and
      experimental studies. However, given the range of factors that can influence
      eutrophication dynamics, and that these matter over a range of time scales, some
      discrete, some continuous, eutrophication dynamics may only be fully investigated
      when long-term, time-series data are available. The present study aims to
      evaluate the interacting effects of abiotic processes and biotic dynamics in
      explaining variations of phytoplankton biomass in a eutrophic shallow lake,
      Barton Broad (Norfolk, UK) using a long-term data set. Multivariate statistical
      analysis shows that the inter-relationships between phytoplankton variability,
      nutrient and grazing factors were highly sensitive to seasonal periodicity. In
      spring phytoplankton biomass was related to phosphorus, nitrogen and silicon. In
      summer phytoplankton biomass was associated with phosphorus, nitrogen and
      zooplankton. In autumn phytoplankton was related to phosphorus, nitrogen, silicon
      and zooplankton. In winter, no significant relationship could be established
      between phytoplankton and environmental variables. This paper improves our
      understanding of the governing role of nitrogen, phosphorus, silicon and
      zooplankton upon phytoplankton variability, and hence, improves management
      methods for eutrophic lakes.

PMID- 11991523
TI  - Steady state critical loads of acidity for sulphur and nitrogen: a multi
      receptor, multi-criterion approach.
AB  - The critical load approach to emission reductions has become an important element
      of the United Nations Economic Commission for Europe (UNECE) Convention on Long
      Range Transboundary Air Pollution (CLRTAP). The steady state mass balance
      approach (SSMB) is the most widely used method in Europe for estimating critical
      loads, typically applied to forest ecosystems on mineral soils in conjunction
      with a base cation to aluminium (Bc:Al) ratio using a default critical limit of
      1.0. The 'typical' approach has been expanded in this paper by: inclusion of a
      broader range of natural and semi-natural receptor ecosystems; inclusion of
      multiple chemical criterion for each receptor; and an attempt to include organic
      soils (peatlands). Critical loads of acidity were estimated for the Republic of
      Ireland using four receptor ecosystems (coniferous forest, deciduous forest,
      natural grasslands and moors and heathlands) and seven chemical criteria. The
      dominant chemical criteria, in the determination of critical loads, were based on
      a critical pH limit for mineral soils or a critical pH shift in relation to
      pristine conditions for organic soils. Approximately 68 and 26% of the final
      distribution of critical loads were estimated using these criteria, respectively.
      The 5th-percentile critical loads of acidity were more sensitive than those
      previously estimated for Ireland due to the inclusion of organic soils.
      Furthermore, coniferous ecosystems had the lowest critical loads due to the high
      percentage occurring on organic soils, and the removal of base cations through
      harvesting. The results demonstrate that it may be more appropriate to use
      multiple criteria and receptors to ensure adequate protection of biological
      indicators. However, it is important that appropriate critical limits are chosen
      to protect the biological indicators and receptor ecosystems from long-term
      damage.

PMID- 11991524
TI  - Comparison of different sampling techniques for the evaluation of pesticide spray
      drift in apple orchards.
AB  - An analytical method using gas chromatography-mass spectrometry has been
      developed for the evaluation of different sampling techniques to characterise
      spray drift in a commercial apple orchard. Eleven pesticides were studied
      (fungicides, insecticides and herbicides). A collection of airborne spray-drift
      pesticides released from a low-profile air-blast orchard sprayer was investigated
      using six types of samplers: (1) a Perkin-Elmer low volume automatic air sampler
      using with glass tube packed with Supelpak-2; (2) a high volume air sampler: (3,
      4) an impinger containing cyclohexane that could be preceded by a glass fibre
      filter; and (5, 6) glass cartridges packed with Supelpak-2 that could be preceded
      by a glass fibre filter. Retention efficiencies of the different sampling
      techniques are compared, and physical forms of the retained pesticides are
      discussed. These techniques have allowed us to evaluate pesticide spray-drift in
      the orchard. Results have shown that the molecules' properties (k(H) and vapour
      pressure) and weather conditions (temperature and relative humidity) strongly
      influence pesticide gas and particles distribution. However, in the studied
      orchard, it is difficult to differentiate pesticide spray-drift and post
      application transfers since treatment duration was > 2 days.

PMID- 11991525
TI  - Occurrence and distribution of linear alkylbenzene sulfonates and
      sulfophenylcarboxylic acids in several Iberian littoral ecosystems.
AB  - The distribution of linear alkylbenzene sulfonates (LAS) and
      sulfophenylcarboxylic acids (SPC) has been characterized in water and sediment of
      five Iberian estuaries and a saltmarsh channel. The highest concentrations of LAS
      and SPC were detected in shallow zones close to discharge points of untreated
      urban effluent, and decreased sharply with increasing distance from these. SPC
      homologues of between 3 and 12 carbon atoms were detected, although their
      concentrations were several orders of magnitude lower than the corresponding LAS.
      The highest SPC concentrations found were of medium carboxylic chain lengths (C6
      C8) in water, and of longer chain lengths (C9-C11) in particulate material. LAS
      homologues were associated preferentially with the particulate material. The
      vertical distribution of LAS in the water column was not homogeneous, in contrast
      to that presented by the SPC homologues. In the case of the Sancti Petri Channel,
      there was a net flow of LAS exportation into the Bay of Cadiz, of -38.6 kg day(
      1), and a net flow for SPC of -6.0 kg day(-1). The daily mass input of LAS and
      their biodegradation intermediates from the Sancti Petri Channel to Cadiz Bay was
      44.6 kg.

PMID- 11991526
TI  - Statistical analysis of environmental data as the basis of forecasting: an air
      quality application.
AB  - A statistical analysis technique is used for the development of an environmental
      forecasting tool. More specifically, a stochastic autoregressive integrated
      moving average (ARIMA) model is developed for maximum ozone concentration
      forecasts in Athens, Greece. For this purpose, the Box-Jenkins approach is
      applied for the analysis of a 9-year air quality observation record. The model
      developed is checked against real data for 1 year. Results show a good index of
      agreement, accompanied by a weakness in forecasting alarms. Finally, suggestions
      are made regarding the enrichment of the approach used in order to improve the
      forecasting performance.

PMID- 11991527
TI  - Temporal trends of Cd, Cu, Hg, Pb and Zn in mussel (Mytilus galloprovincialis)
      from the Spanish North-Atlantic coast 1991-1999.
AB  - Temporal trends for heavy metals (Cd, Cu, Hg, Pb and Zn) in mussel (Mytilus
      galloprovincialis) from the Galician and Cantabrian areas in Spain, where samples
      were yearly collected from 1991 to 1999, are presented. This study was carried
      out by the Centro Oceanografico de Vigo of the Instituto Espanol de Oceanografia
      (I.E.O.) as part of the Spanish contribution to the Joint Assessment and
      Monitoring Programme (JAMP) of the OSPAR Convention. The experimental work and
      subsequent statistical treatment, following OSPAR procedures and guidelines, are
      described. In order to carry out the statistical treatment of the data, median
      values of the different shell length classes were used for each contaminant, year
      and area. The Kendall T-b correlation coefficient was used with the purpose of
      demonstrating the existence of a downward significant temporal trend in the
      pollution levels, according to the advice of ICES Working Group on Statistical
      Aspects of Environmental Monitoring. A decrease of copper levels was detected in
      Vigo, Pontevedra and Arosa, of mercury in Pontevedra and A Coruna, of lead in
      Vigo, Pontevedra, A Coruna and Bilbao and of zinc in Pontevedra and A Coruna.
      However, a cadmium positive trend was registered at Ria de Vigo. No significant
      trends were detected in the other cases.

PMID- 11991528
TI  - A new method for determination of halogenated flame retardants in human milk
      using solid-phase extraction.
AB  - A method has been developed for quantitation of a selection of halogenated flame
      retardants in human milk. The method has been validated for seven polybrominated
      diphenyl ethers (PBDEs), BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, and
      BDE-183, and the halogenated phenols 2,4,6-tribromophenol (TriBP),
      pentabromophenol (PeBP), tetrachlorobisphenol-A (TCBP-A), and tetrabromobisphenol
      A (TBBP-A). The sample preparation includes solid-phase extraction using an N
      vinylpyrrolidone-divinylbenzene copolymer with on-column lipid decomposition
      followed by additional cleanup on sulfuric acid-silica columns and methylation of
      the phenolic compounds. Separation and detection were performed by gas
      chromatography-electron capture mass spectrometry, using a 5% phenyl 95%
      dimethylpolysiloxane column. The method has been validated in the range of 1.8
      180 pg/g milk for most of the halogenated flame retardants. The average absolute
      recoveries were from 49 to 83%, and the average recoveries with respect to
      internal standards were in the range of 53 to 121%. Estimated limits of detection
      were in the range of 0.3 to 1.0 pg/g milk using a sample size of 5 g for all
      compounds, except TCBP-A, for which the limit of detection was estimated to 6.7
      pg/g milk.

PMID- 11991529
TI  - Gas chromatography-mass spectrometry analysis of 4-O-methylpyridoxine (MPN) in
      the serum of patients with ginkgo seed poisoning.
AB  - The 4-O-methylpyridoxine (MPN) present in the seeds of the Ginkgo biloba
      (maidenhair tree) has anti-vitamin B6 actions, and ginkgo seed poisoning can
      induce convulsions. We developed a specific quantitative method using gas
      chromatography-mass spectrometry for the analysis of MPN in human serum. The
      trifluoroacyl (TFA) derivative of MPN was obtained by treating MPN with
      trifluoroacetic anhydride at 50 degrees C for 5 min and remained stable for 6 h.
      The calibration curve of standard MPN obtained in the selective ion mode using
      the base ion (m/z 343) was linear between 100 pg and 10 ng, and the detection
      limit was 50 pg. The full mass spectrum of 100 pg of the TFA derivative of MPN
      was obtained easily. MPN was extracted from the serum with the use of a C18 solid
      phase extraction cartridge. The recovery rate of MPN added to the serum at a
      concentration of 0.1 microg/mL was 90.0%.

PMID- 11991530
TI  - Determination of blood cyanide by HPLC-MS.
AB  - An original high-performance liquid chromatographic-mass spectrometric (HPLC-MS)
      procedure was developed for the determination of cyanide (CN) in whole blood.
      After the addition of K13C15N as internal standard, blood was placed in a
      microdiffusion device, the inner well of which was filled with a mixture of
      taurine (50mM in water)/naphthalene-2,3-dicarboxaldehyde (NDA, 10mM in
      methanol)/methanol/ concentrated (approximately 20%) ammonia solution
      (25:25:45:5, v/v). Concentrated H2SO4 was added to the blood sample, and the
      microdiffusion chamber was sealed. After 30 min of gentle agitation, 2 microL of
      the contents of the inner vial were pipetted and directly injected onto a NovaPak
      C18 HPLC column. Separation was performed by a gradient of acetonitrile in 2mM
      NH4COOH, pH 3.0 buffer (35-80% in 10 min). Detection was done with a Perkin-Elmer
      Sciex API-100 mass analyzer with an ionspray interface, operated in the negative
      ionization mode. MS data were collected as either TIC or SIM at m/z (299 + 191)
      and (301 + 193) for the derivatives formed with CN and 13C15N, respectively.
      Inspired by previous works dealing with the complexation of CN by NDA + taurine
      to form a 1-cyano [f] benzoisoindole derivative analyzed by HPLC-fluorimetry,
      this method appears simple, rapid, and extremely specific. Limits of detection
      and quantitation for blood CN are 5 and 15 ng/mL, respectively. The use of 13C15N
      as internal standard allows the quantitation of CN with elegance and accuracy in
      comparison with previously reported methods.

PMID- 11991531
TI  - Advances in the use of mass spectral libraries for forensic toxicology.
AB  - Gas chromatography in combination with mass spectrometry (GC-MS) plays an
      important role in the field of analytical toxicology. The identification of
      unknown compounds is very frequently undertaken with GC-MS and utilizing mass
      spectral libraries. Currently available libraries for analytical toxicology were
      compared for overlapping and uniqueness of their entries. Furthermore, the widely
      known Pfleger-Maurer-Weber-Drugs-and-Pesticides-Library for toxicology (PMW_tox2)
      was used to compare the search algorithms PBM (Probability Based Matching,
      Agilent Technologies), INCOS (Finnigan/Thermoquest), and MassLib (Max Planck
      Institute). To our knowledge, direct comparisons of mass spectral libraries and
      search programs for analytical toxicology have not been published previously. The
      capabilities and necessities of modern MS technology in the field of general
      unknown analysis are revealed, and some of the potential pitfalls are described.

PMID- 11991532
TI  - Determination of MDMA and its metabolites in blood and urine by gas
      chromatography-mass spectrometry and analysis of enantiomers by capillary
      electrophoresis.
AB  - A gas chromatography-mass spectrometry (GC-MS) method was used for the
      simultaneous quantitation of 3,4-methylenedioxymethamphetamine (MDMA) and the 3,4
      methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4
      hydroxy-3-methoxyamphetamine (HMA) metabolites in plasma and urine samples after
      the administration of 100 mg MDMA to healthy volunteers. Samples were hydrolyzed
      prior to a solid-phase extraction with Bond Elut Certify columns. Analytes were
      eluted with ethyl acetate (2% ammonium hydroxide) and analyzed as their
      trifluoroacyl derivatives. Linear calibration curves were obtained at plasma and
      urine concentration ranges of 25-400 ng/mL and 250-2000 ng/mL for MDMA and HMMA,
      and of 2.5-40 ng/mL and 100-1000 ng/mL for MDA and HMA. Following the same urine
      preparation procedure but without the derivatization step, a capillary
      electrophoresis (CE) method for enantiomerical resolution of compounds was
      developed using (2-hydroxy)propyl-beta-cyclodextrin at two different
      concentrations (10 and 50mM in 50mM H3PO4, pH 2.5) as chiral selector.
      Calibration curves for the CE method were prepared with the corresponding racemic
      mixture and were linear between 125 and 2000 ng/mL, 50 and 1000 ng/mL, and 125
      and 1500 ng/mL for each enantiomer of MDMA, MDA, and HMMA, respectively.
      Stereoselective disposition of MDMA and MDA was confirmed. HMMA disposition seems
      to be in apparent contradiction with MDMA findings as the enantiomer ratio is
      close to 1 and constant over the time.

PMID- 11991533
TI  - Automated homogeneous immunoassay analysis of cotinine in urine.
AB  - A study was conducted to evaluate the performance comparison of a homogeneous
      enzyme immunoassay (EIA) designed to detect cotinine in urine and carbon monoxide
      (CO) breath measurements to determine smoking status. The clinical comparison was
      done using urine and breath specimens from 218 volunteers. Urine samples were
      analyzed by immunoassay and confirmed by gas chromatography-mass spectrometry (GC
      MS). Breath carbon monoxide was determined by a commercial analyzer. Using
      cutoffs of 10 ppm for CO and 500 ng/mL for urinary cotinine, the relative
      sensitivity/specificity was 93.6%/74.0%. The positive predictive value was 86.8%,
      and the negative predictive value was 86.5%. However, comparison of the EIA to GC
      MS showed a sensitivity/specificity of 96.2%/98.4% and a positive predictive
      value of 99.3%. The EIA was also evaluated non-clinically for precision,
      stability, recovery, and interferences. In addition, the non-clinical evaluation
      demonstrated coefficients of variation from 0.37 to 1.09% across cotinine
      concentrations ranging from 0 to 5000 ng/mL. The assay was found to be highly
      specific for cotinine and cross-reacted to a limited degree with 3
      hydroxycotinine. Finally, multiple freeze-thaw cycles of urines containing
      cotinine showed no degradation of the drug in the specimen when tested in the
      EIA. Thus, the EIA tested is a rapid, lab-based test that can reliably determine
      cotinine levels and their relation to smoking status.

PMID- 11991534
TI  - The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone,
      6-acetylmorphine, and oxycodone in hair and oral fluid.
AB  - Recently, the abuse of prescription opiates as alternatives to heroin has become
      a national concern. The determination of a six-drug opiate panel, codeine,
      morphine, 6-acetylmorphine, hydrocodone, hydromorphone, and oxycodone, in hair
      and oral fluid using solid-phase extraction and capillary gas chromatography-mass
      spectrometry (GC-MS) is described. Oral fluid was obtained from the donor by
      insertion of absorptive collectors into the mouth. Hair was collected from the
      patient and powdered using stainless steel ball bearings in a mini bead-beater
      apparatus. Opiates present in the samples were extracted from a buffered, aqueous
      matrix using a solid-phase cartridge. The extracts were concentrated and the
      methoxime/BSTFA derivatives prepared in order to eliminate interference from the
      keto-opiates. The extracts were separated by GC-MS in electron impact mode. By
      utilizing methoxyamine, we were able to produce the methoxime derivatives
      required for single derivative production and chromatographically separate all
      six opiates. The routine analysis of these opiates in hair and oral fluid using
      GC-MS is described for the first time.

PMID- 11991535
TI  - Method for the determination of dialkyl phosphates in urine by strong anion
      exchange disk extraction and in-vial derivatization.
AB  - A method for the determination of four dialkylphosphate metabolites in urine by
      strong anion exchange disk (SAX) was investigated. Calcium hydroxide was added to
      a 1-mL urine sample to reduce interference. The aliquot was passed through the
      SAX disk to accumulate dialkylphosphate metabolites on the disk. The retained
      dialkylphosphate metabolites were derivatized with methyl iodide in acetonitrile
      online, and the resulting methyl esters of dialkylphosphate metabolites were
      directly analyzed by capillary column gas chromatography with flame photometric
      detection. The recoveries of these dialkylphosphate metabolites were found to be
      stable. When the intact sample was diluted with deionized water at a 1:1 ratio,
      the recoveries were both increased and stabilized. The urine samples collected
      from eight fruit farmers showed that levels of dialkylphosphate metabolites in
      urine were significantly different before and after pesticide application,
      indicating the method established in this study is applicable for real sample
      analysis. Compared with previous studies, this method not only can greatly
      simplify sample preparation, but it can also significantly reduce the consumption
      of toxic solvents in sample preparation.

PMID- 11991536
TI  - Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by
      HPLC and fluorescence detection following LSD ImmunElute extraction.
AB  - In all, 3872 urine specimens were screened for lysergic acid diethylamide (LSD)
      using the CEDIA DAU LSD assay. Forty-eight samples, mainly from psychiatric
      patients or drug abusers, were found to be LSD positive, but only 13 (27%) of
      these could be confirmed by high-performance liquid chromatography with
      fluorescence detection (HPLC-FLD) following immunoaffinity extraction (IAE).
      Additional analysis for LSD using the DPC Coat-a-Count RIA was performed to
      compare the two immunoassay screening methods. Complete agreement between the DPC
      RIA assay and HPLC-FLD results was observed at concentrations below a cutoff
      concentration of 500 pg/mL. Samples that were LSD positive in the CEDIA DAU assay
      but not confirmed by HPLC-FLD were also investigated for interfering compounds
      using REMEDI HS drug-profiling system. REMEDI HS analysis identified 15 compounds
      (parent drugs and metabolites) that are believed to cross-react in the CEDIA DAU
      LSD assay: ambroxol, prilocaine, pipamperone, diphenhydramine, metoclopramide,
      amitriptyline, doxepine, atracurium, bupivacaine, doxylamine, lidocaine,
      mepivacaine, promethazine, ranitidine, and tramadole. The IAE/HPLC-FLD
      combination is rapid, easy to perform and reliable. It can reduce costs when
      standard, rather than more advanced, HPLC equipment is used, especially for labs
      that perform analyses for LSD infrequently. The chromatographic analysis of LSD,
      nor-LSD, and iso-LSD is not influenced by any of the tested cross-reacting
      compounds even at a concentration of 100 ng/mL.

PMID- 11991537
TI  - Use of transgenic models to understand effects of exercise on glucose metabolism.
AB  - This review will focus on the achievements obtained using transgenic animals in
      our understanding of exercise-induced insulin sensitivity as well as the
      regulation of glycogen storage in skeletal muscle, including the effects of acute
      exercise and insulin on the major determinants: glycogen synthesis and glucose
      uptake.

PMID- 11991538
TI  - Neural control of motor output: can training change it?
AB  - Henneman's size principle of motor unit recruitment and rate coding reduces
      fatigue, minimizes error in transfer of information from the nervous system, and
      produces smooth force output. Plasticity present at various sites of the motor
      system may change endurance, force, speed, or precision with training, but not
      the recruitment order.

PMID- 11991539
TI  - Telephone-assisted counseling for physical activity.
AB  - Different methods of intervention have been tested to promote physical activity
      at the individual level. The telephone is an excellent form of media for
      delivering exercise counseling and advice. This review highlights important
      clinical trials that have documented the success of telephone-assisted exercise
      counseling for promoting physical activity in a variety of populations.

PMID- 11991540
TI  - Exercise-induced changes in diaphragmatic bioenergetic and antioxidant capacity.
AB  - The primary inspiratory muscle in mammals is the diaphragm. Endurance exercise
      elevates both the oxidative and antioxidant capacity of the costal and crural
      diaphragm. These exercise-induced changes in oxidative and antioxidant capacity
      occur rapidly after the onset of training and are associated with reduced
      oxidative injury and improved diaphragmatic endurance.

PMID- 11991541
TI  - Exercise enhances and protects brain function.
AB  - Physical activity, in the form of voluntary wheel running, induces gene
      expression changes in the brain. Animals that exercise show an increase in brain
      derived neurotrophic factor, a molecule that increases neuronal survival,
      enhances learning, and protects against cognitive decline. Microarray analysis of
      gene expression provides further support that exercise enhances and supports
      brain function.

PMID- 11991542
TI  - Muscle structural capacity for oxygen flux from capillary to fiber mitochondria.
AB  - The concept of major functional resistance to O2 flux at the capillary-fiber
      interface implies that muscle structural capacity for O2 flux from capillary to
      fiber mitochondria needs to be assessed in terms of capillary surface per fiber
      surface. Morphological data support this notion and show the importance of
      assessing the size of the capillary-fiber interface relative to muscle fiber O2
      demand.

PMID- 11991543
TI  - Modulation of insulin signaling in human skeletal muscle in response to exercise.
AB  - Exercise is widely recommended for the treatment of obesity, insulin resistance,
      and type II diabetes mellitus. Recent discoveries in the molecular and cellular
      regulation of insulin-mediated glucose metabolism in skeletal muscle have
      provided a deeper understanding of how exercise modulates insulin action.

PMID- 11991544
TI  - Regulation of pyruvate dehydrogenase (PDH) activity in human skeletal muscle
      during exercise.
AB  - Pyruvate dehydrogenase is a mitochondrial multienzyme complex that catalyzes the
      conversion of pyruvate to acetyl-coenzyme A and regulates the entry of
      carbohydrate into the tricarboxylic acid cycle for oxidation. During exercise,
      pyruvate dehydrogenase activation in human skeletal muscle is proportional to the
      relative aerobic power output (percent VO2max) and is regulated by increases in
      Ca2+, free ADP, and pyruvate concentrations.

PMID- 11991545
TI  - The role of leukotrienes in upper and lower airway inflammation and the
      implications for treatment.
AB  - OBJECTIVE: This article reviews the proinflammatory effects of the cysteinyl
      leukotrienes (CysLTs) in the upper and lower airways, along with evidence of
      their role in allergic rhinitis and chronic hyperplastic sinusitis with nasal
      polyposis (CHS/NP). After reading this article, readers should have a greater
      understanding of the effects of the CysLTs on both upper and lower airways and
      their implications for treatment. DATA SOURCES: Relevant and appropriately
      controlled studies on the inflammatory processes associated with leukotrienes
      (LTs) were reviewed. Only literature in the English language was reviewed. STUDY
      SELECTION: Material was taken from peer-reviewed journals and data generated from
      the author's laboratory. RESULTS: The CysLTs possess proinflammatory effects that
      contribute to the increase of tissue eosinophilia. Emerging data support their
      importance in diseases of the upper airways, including allergic rhinitis and
      CHS/NP. The LT modifiers may be appropriate agents for treating inflammatory
      disorders of the upper airways because of their proven effectiveness in reducing
      inflammation in asthma. Results from studies in patients with allergic rhinitis
      demonstrated improved nasal rhinorrhea, sneezing, and congestion. LT modifiers
      have improved nasal congestion and restored the sense of smell in patients with
      CHS/NP. CONCLUSIONS: The LT receptor antagonists have proven to be an effective
      antiinflammatory treatment for asthma. Emerging data indicate that LTs play a
      pivotal role in inflammatory upper airway disease, providing a growing rationale
      for the use of LT receptor antagonists to treat allergic rhinitis and CHS/NP.

PMID- 11991546
TI  - The burden of allergic rhinitis: beyond dollars and cents.
AB  - OBJECTIVE: This article presents information about the economic burden of
      allergic rhinitis and its effect on quality of life. After reading this article,
      readers should have a greater awareness of the economic impact of this disease
      and how important it is for both patient and society to diagnose and treat it
      properly. DATA SOURCES: Relevant and appropriately controlled clinical studies,
      data compiled from surveys and patient questionnaires, and studies of direct and
      indirect costs associated with allergic rhinitis were used. Only literature in
      the English language was reviewed. STUDY SELECTION: Material was taken from
      academic/scholarly journals and appropriate reviews. RESULTS: Allergic rhinitis
      occurs in approximately 20% of the general population in the United States. In
      recent years, its economic impact has increased, with spending for direct and
      indirect medical costs estimated between 1.5 and $2 billion a year. In addition
      to its financial burden, however, allergic rhinitis exacts a considerable toll on
      patients' quality of life, cognitive and learning functions, decision-making, and
      self-perception. Low energy levels associated with allergic rhinitis can lead to
      impairments of both memory and decision-making abilities. CONCLUSIONS: Effective
      treatment and greater understanding on the part of both physicians and patients
      can help to reduce direct and indirect costs as well as to lessen the impact of
      allergic rhinitis on quality of life for both patient and society.

PMID- 11991547
TI  - Clinical evidence for antileukotriene therapy in the management of allergic
      rhinitis.
AB  - OBJECTIVE: This article presents information summarizing the findings of several
      clinical trials that evaluated the efficacy and safety of leukotriene receptor
      antagonists in the treatment of allergic rhinitis. After reading this article,
      readers will have a greater understanding of these clinical findings and their
      implications for the management of allergic rhinitis. DATA SOURCES: Relevant and
      appropriately controlled clinical trials were used. Only literature in the
      English language was reviewed. STUDY SELECTION: Material was taken from
      academic/scholarly publications, published abstracts, and papers presented at a
      major congress. RESULTS: Similar to their contribution to the pathogenesis of
      asthma, cysteinyl leukotrienes have been found to exert potent inflammatory
      effects in the upper airways and to play a role in the pathogenesis of allergic
      rhinitis. The guidelines for the diagnosis and treatment of allergic rhinitis
      emphasize the importance of treating the pathophysiologic pathways of the
      disease. Thus, the use of antileukotriene therapy is a rational therapeutic
      option for patients with allergic rhinitis. Findings from several randomized,
      placebo-controlled clinical trials confirm the efficacy of leukotriene receptor
      antagonists in reducing the symptoms of allergic rhinitis and improving quality
      of life. Clinical experience with these medications has also demonstrated their
      tolerability and safety. CONCLUSIONS: Results from recently completed and ongoing
      clinical trials have expanded the body of evidence for the safety and efficacy of
      antileukotrienes in the treatment of allergic rhinitis.

PMID- 11991548
TI  - Rethinking our approach to allergic rhinitis management.
AB  - OBJECTIVE: This article reviews the recommendations by the World Health
      Organization's new guidelines, "Allergic Rhinitis and Its Impact on Asthma"
      (ARIA), and the paradigm for treating allergic rhinitis based on disease
      classification. After reading this article, readers should understand the ARIA
      guidelines and the salient issues involving the challenges inherent in the
      management of allergic rhinitis. DATA SOURCES: Relevant and appropriately
      controlled clinical studies and results of patient surveys were used. Only
      literature in the English language was reviewed. STUDY SELECTION: Material was
      taken from academic/scholarly journals, published abstracts, and presentations at
      a major congress. RESULTS: The ARIA guidelines' new classification categorizes
      patients' allergic rhinitis as either intermittent or persistent with gradations
      from mild to moderate-severe. These guidelines propose a stepwise approach to
      management guided by symptom severity and evaluation of treatment response, with
      the underlying concept for treatment being to select therapies that address
      individual patients' symptoms. Although few data were available at the time of
      their inception, the guidelines recognize that antileukotriene medications may
      play an important role in the treatment of allergic rhinitis. Results of recent
      clinical trials support the use of antileukotriene medications in allergic
      rhinitis, alone or concomitantly with an antihistamine. CONCLUSIONS: Targeting
      specific and multiple mechanisms of allergic rhinitis and individualizing all
      available and effective treatments to each patient, with specific medications for
      specific symptoms, will be of particular benefit to patients with allergic
      rhinitis.

PMID- 11991549
TI  - Upper airway disorders and asthma: a syndrome of airway inflammation.
AB  - OBJECTIVE: This article presents recent evidence of an upper and lower airway
      link. After reading this article, readers should have an understanding of the
      evidence for the pathologic relationship between asthma and upper airway
      disorders such as rhinosinusitis and allergic rhinitis. DATA SOURCES:
      Epidemiologic, pathophysiologic, and treatment outcomes studies were used. Only
      literature in the English language was reviewed. STUDY SELECTION: Material was
      taken from academic/scholarly journals. RESULTS: Epidemiologic data indicate that
      asthma and allergic rhinitis frequently coexist, with rhinitis symptoms reported
      among 19 to 94% of asthma patients, and asthma reported among 19 to 38% of those
      with allergic rhinitis. Allergic rhinitis often precedes asthma symptomatology
      and has been shown to be a risk factor for the development of asthma. The
      severity of one's allergic rhinitis also has been shown to be directly correlated
      with asthma severity. Patients with allergic rhinitis exhibit increased
      eosinophil activity in both upper and lower airways. In these patients, nasal
      allergen challenge can induce increased bronchial hyperresponsiveness, suggesting
      that upper and lower airway disorders share common inflammatory features.
      Treatment of rhinitis symptoms has been shown to produce better asthma symptom
      control and, in a few studies, the improvement of airway function in patients
      with concomitant asthma. CONCLUSIONS: Evidence suggests that upper respiratory
      disorders such as allergic rhinitis and rhinosinusitis are different facets of a
      larger systemic inflammatory syndrome involving both the upper and lower airways.
      Several important questions remain to be answered before the nature of the
      relationship between lower and upper airway disorders is fully understood.

PMID- 11991550
TI  - Endothelin-1: a useful marker for asthmatic inflammation?

PMID- 11991551
TI  - Skin testing: making the most of every prick.

PMID- 11991552
TI  - Clinical update on peanut allergy.
AB  - BACKGROUND: Peanut allergy is common, potentially severe, and there has been a
      recent surge in clinical investigation of this important food allergen.
      OBJECTIVE: To provide the reader with a clinically oriented update on peanut
      allergy. DATA SOURCES: English language articles were selected from PubMed
      searches (search terms: peanut allergy, food allergy, anaphylaxis) and selected
      abstracts with a bias toward recent (3 years) studies judged to have immediate,
      practical clinical implications. RESULTS: Peanut allergy is an increasing problem
      in western diets that include this food. Both genetic and environmental factors
      influences the expression of this allergy. The at-risk subject is an atopic
      individual, with heightened risk for those with atopic dermatitis and/or other
      food allergies. The allergy is long-lived for most, may increase slightly in
      severity over time, but approximately 20% of young children will develop
      tolerance. Parameters that may identify the subset likely to achieve tolerance
      have been identified. Several large studies have determined laboratory parameters
      (skin tests, peanut-specific serum immunoglobulin E concentrations) with
      excellent predictive value (>95%) to diagnose current clinical reactivity or
      tolerance, although oral food challenges are necessary for a definitive
      diagnosis. Numerous practical lessons concerning management (avoidance,
      treatment, and prevention) have been identified. CONCLUSIONS: Recent studies
      provide the clinician with an armament of improved diagnostic and treatment
      modalities for peanut allergy. Studies are underway that are likely to provide
      more definitive therapies in the near future.

PMID- 11991553
TI  - A 47-year-old woman with progressive dyspnea and cough.

PMID- 11991554
TI  - Plasma endothelin-1 immunoreactivity in asthmatic children.
AB  - BACKGROUND: Endothelin-1 (ET-1) has been formerly demonstrated to have potent
      vasocontractile as well as bronchoconstrictor effects in vitro. This followup
      study was aimed to evaluate the possible changes in ET-1 levels in the plasma of
      asthmatic children, according to disease activity and severity. METHODS: Plasma
      ET-1 was estimated by enzyme-linked immunoadsorbent assay in 30 asthmatic
      patients (6 to 12 years old) during and after remission of an acute attack.
      Thirty age- and sex-matched healthy children were included as a control group.
      RESULTS: Plasma ET-1 immunoreactivity was significantly increased in the
      asthmatic children during the attacks (17.2+/-6.9 pg/mL) in comparison to the
      levels during quiescence of symptoms (0.9+/-1.13 pg/mL). Further, both values
      were significantly higher than the control value (0.22+/-0.29 pg/mL). The
      severity of attacks as judged clinically and by peak expiratory flow rate
      measurement did not influence the plasma endothelin status; neither did the
      family history of atopy nor the absolute eosinophil count. However, serum total
      IgE levels could be positively correlated to the plasma endothelin concentrations
      measured after remission of the asthmatic attacks (P < 0.05). CONCLUSIONS: Our
      findings reinforce the concept that ET-1 may be implicated in the pathogenesis of
      bronchoconstriction. This may encourage further studies on the value of ET-1
      antagonism among alternative therapeutic modalities of childhood asthma.

PMID- 11991555
TI  - A comparison of two skin test methodologies and allergens from two different
      manufacturers.
AB  - BACKGROUND: Skin prick tests (SPTs) are a frequently used method for evaluation
      of atopy. A variety of standard allergen preparations are available, together
      with a number of different methods of application. OBJECTIVE: The objective of
      this study was to compare SPT reactivity 1) using Soluprick SQ allergens (ALK
      Allergologisk Laboratorium A/S, Horsholm, Denmark) and Bayer allergens [Bayer
      Corporation, West Haven, CT], and 2) using two common methods of application, a
      standard prick lancet and a Quintest, both produced by Bayer. METHODS: SPTs were
      undertaken on 22 adult volunteers (mean age 40 years, 17 female, 5 male). Wheal
      size was recorded as mean diameters (mm) and area (mm2). RESULTS: Bayer allergens
      produced larger mean diameters and areas to dust mites than ALK allergens, with
      the differences significant when allergens were applied with the lancet. There
      was a tendency for the ALK cat allergen to produce larger reactions than the
      Bayer product. The method of application also influenced the wheal size, with the
      lancet producing significantly larger mean diameters than the Quintest for the
      histamine and allergens from both manufacturers, except the ALK cat allergen.
      There were similar differences between methods of application for reactions
      measured as an area. CONCLUSIONS: SPTs that use different allergens or different
      methods of application will not provide comparable assessments of atopy.

PMID- 11991556
TI  - Factors affecting compliance with allergen immunotherapy at a military medical
      center.
AB  - BACKGROUND: Allergen immunotherapy (AIT) is a safe and effective treatment for
      certain allergic disorders; however, noncompliance with therapy is common. We
      evaluated the compliance rates among groups receiving AIT at a military medical
      center and identified factors affecting compliance. METHODS: The charts of the
      381 actively enrolled patients in our AIT program were evaluated for patient
      compliance. Noncompliant patients were contacted to determine the reason for
      stopping therapy. Patients were then grouped by diagnosis, age, sex, military
      status, and schedule of AIT and evaluated for differences. RESULTS: The overall
      compliance rate was 77.4%. The most common reasons for noncompliance included
      inconvenience, precluding medical condition, and adverse systemic reaction. There
      were no differences in compliance rates by diagnosis or sex. Noncompliant
      patients were younger than compliant patients, 35.4 years versus 42.4 years (P =
      0.001); however, when patients were divided into three age categories (<18, 18 to
      45, and >45 years), the youngest and oldest groups were more compliant (P <
      0.001). Active-duty members were less compliant than retirees and family members,
      65.7% versus 83.1% and 81.4%, respectively (P = 0.004). Patients receiving a
      conventional schedule of AIT were more compliant than those on a rush schedule,
      80.0% versus 48.4% (P < 0.001). CONCLUSIONS: Factors found to affect patient
      compliance with an AIT regimen at our military medical center include age,
      military status, and schedule of AIT. The most common reasons for noncompliance
      included inconvenience, precluding medical conditions, and adverse systemic
      reactions. Clinicians need to be aware of the factors limiting patient compliance
      with AIT in an attempt to maximize treatment effectiveness.

PMID- 11991557
TI  - Does introduction of new "easy to use" inhalational devices improve medical
      personnel's knowledge of their proper use?
AB  - BACKGROUND: Lack of basic inhaler skills by medical personnel has been documented
      by numerous studies. Consequently, training of patients in correct inhalational
      technique suffers. Newer dry powder inhalers such as Turbuhaler (budesonide,
      Astra USA, Westborough, MA) and Diskus (salmeterol, GlaxoSmithKline, Research
      Triangle Park, NC) have some advantages over conventional metereddose inhalers
      (MDIs) including easier technique of usage. They have been recently marketed with
      the hope of overcoming this problem. OBJECTIVE: To determine whether introduction
      of newer "easy to use" dry powder inhalers such as budesonide (Turbuhaler) and
      salmeterol (Diskus) would result in improvement in medical personnel's knowledge
      of their proper use. METHODS: In and around a community-based teaching hospital,
      interviews were conducted in March 2000 of 50 assorted randomly selected medical
      personnel. They included 10 respiratory therapists, 10 registered nurses, 10
      medical residents, 10 primary care physicians, and 10 pharmacists. Objective
      evaluation was made of their skills demonstration and knowledge scores for usage
      of MDIs, budesonide, and salmeterol. RESULTS: Mean percentage demonstration
      scores of different medical personnel for all three devices taken together:
      respiratory therapist (81.6%), primary care physicians (77.7%), pharmacists
      (57.7%), registered nurses (54.4%), and medical residents (53.8%). Mean
      percentage demonstration scores of different inhalers for all medical personnel
      taken together: MDI (80.9%), salmeterol (64.2%), budesonide (49.9%). Mean
      percentage knowledge score of all three inhalational devices taken together for
      respiratory therapist was the best at 76.6%. Registered nurses performed the
      worst with a score of 52.0%. Mean percentage knowledge scores: MDI (78%),
      salmeterol (63.2%), and budesonide (52.4%). A repeated measures two-way analysis
      of variance demonstrated that differences in both demonstration and knowledge
      scores between inhaler types and between medical personnel were all highly
      statistically significant (P < 0.0001). CONCLUSIONS: Demonstration skills and
      knowledge scores for use of both budedsonide and salmeterol were substantially
      lower than that for MDI for all medical personnel. Medical personnel responsible
      for teaching the correct use of inhalational devices are lacking in basic
      knowledge and user skills. This likely contributes to patient's poor technique
      when using these devices.

PMID- 11991558
TI  - Loss of response to treatment with leukotriene receptor antagonists but not
      inhaled corticosteroids in patients over 50 years of age.
AB  - BACKGROUND: There are limited published data describing the relative efficacy of
      available treatment options in younger versus older patients with persistent
      asthma. OBJECTIVE: To compare the efficacy of fluticasone propionate (FP) and
      zafirlukast (Z) in younger (12 to 49 years of age) versus older (50 years and
      older) patients with asthma. METHODS: A retrospective analysis of five
      randomized, double-blind, double-dummy studies 4 to 12 weeks in duration of 1,742
      patients <50 years of age and 243 patients aged 50 years or older. Interventions
      were inhaled fluticasone propionate (FP) 88 microg, oral Z 20 mg, or placebo
      twice daily. RESULTS: Treatment with FP resulted in significantly greater
      improvements than Z in all efficacy measurements (except for nighttime
      awakenings) regardless of age. In older patients, treatment with FP significantly
      increased pulmonary function compared with Z: FEV (FP= +0.19 L; placebo = -0.34
      L; Z = -0.06 L); AM peak expiratory flow rate [PEFR] (FP = +25 L/minute; placebo
      = -18 L/minute; Z = +4 L/minute); PM PEFR (FP = +24 L/minute; placebo = -24
      L/minute; Z = +5 L/minute; P < or = 0.023; for all comparisons). Compared with Z,
      treatment with FP in older patients also resulted in significantly greater
      increases in the percentage of symptom-free days (25% vs 13%) and rescue-free
      days (35% vs 17%); and significantly greater reductions in albuterol use (-1.6 vs
      -0.3 puffs/day) and the percentage of patients with exacerbations (2.7% vs 14.3%;
      P < or = 0.031). CONCLUSIONS: Regardless of age, treatment with FP in patients
      with asthma significantly improved pulmonary function and overall asthma control.
      In contrast, treatment with Z in older patients with asthma resulted in small
      improvements in asthma symptoms, whereas lung function improved minimally or not
      at all, and exacerbations increased. These data suggest that FP effectively
      controls inflammation in older patients, whereas Z may mask inflammation and may
      not provide the level of bronchodilatory or anti-inflammatory activity needed for
      effective asthma control in older patients.

PMID- 11991559
TI  - Relationship among house-dust mites, Der 1, Fel d 1, and Can f 1 on clothing and
      automobile seats with respect to densities in houses.
AB  - BACKGROUND: Locations where there are no dust mites or pets present may contain
      allergens that pose a risk factor for sensitizing and inducing rhinitis and
      asthma. OBJECTIVE: The purpose of this study was to investigate the relationship
      among the prevalence of mites and mite, dog, and cat allergens in homes, on
      clothing, and on automobile seats. METHODS: Over a 2-year period (July 1998 to
      July 2000), dust mite and mite, dog, and cat allergen densities were determined
      in homes, associated automobiles, and on the clothing of the drivers. During this
      period 87 homes were sampled one to five times each. RESULTS: Low levels of live
      and dead mites were present in most dust samples obtained from automobile seats
      and in 16% from clothing. Seventy-two and 50% of the home samples had >2 microg
      and >10 microg Der l/g of dust, respectively, whereas 23% of automobiles seat
      samples had >2 microg Der l/g of dust with a mean of 1.3 microg/g. Mite and Der 1
      densities were not different for homes with or without pets. However, homes with
      pets had significantly more Fel d 1 or Can f 1 allergen than homes without pets.
      Homes without cats and dogs had an average of 93 and 29 microg/g of Fel d 1 and
      Can f 1, respectively, which was well above threshold levels for sensitization
      and induction of allergic reactions. Although most clothing had detectable levels
      of pet allergen, the levels of these allergens were low. CONCLUSIONS: Der 1
      densities in some automobiles were sufficiently high (>2 microg/g of dust) to be
      risk factors for sensitization and allergic reactions. However, most automobile
      seats had levels of dog and cat allergen that were well above the threshold
      levels considered to be risk factors for both sensitization and symptoms,
      regardless of the presence of a pet in the home. The presence of live and dead
      mites and mite, cat, and dog allergens in automobiles and on clothing suggests
      that both are vehicles in the dispersal of mites and mite and pet allergen.

PMID- 11991560
TI  - Comparison of positive allergy skin tests among asthmatic children from rural and
      urban areas living within small geographic area.
AB  - BACKGROUND: Evidence of increased asthma and allergic response among urban versus
      rural residents has been reported. OBJECTIVE: To evaluate the prevalence of
      allergic response among asthmatic children from urban and rural areas living
      within close proximity. METHODS: In all, 448 asthmatic children from urban (363)
      and rural (85) areas were studied. The study group consisted of 234 9-year-olds
      and 214 12-year-olds. A health questionnaire was completed on each child who
      subsequently underwent allergic skin prick tests (SPTs). RESULTS: There was
      significantly more positive SPT response to house-dust mite, mold, cat, and
      cypress among asthmatic children from urban areas compared with children living
      in rural areas: 58.3% versus 37.6%, 46.1% versus 31.8%, 17.45 versus 5.9%, and
      26.2% versus 15.3%, respectively. Positive SPT for indoor allergens were
      significantly greater among asthmatic urban residents than asthmatic rural
      residents: 63.3% versus 45.5%, respectively (P < 0.02). Positive SPT response to
      all the allergens checked was higher among the 12-year-old age group when
      compared with the 9-year-olds, 34.6% versus 22.7%, respectively (P = 0.05).
      CONCLUSIONS: Allergic response measured by SPT is significantly more common among
      asthmatic children from urban areas as opposed to rural, even though both areas
      are within small distance of one another. Further, asthmatic children living in
      urban areas demonstrated more allergic response to both indoor and outdoor
      allergens. The allergic response tends to increase with increased age in both
      urban and rural asthmatic children.

PMID- 11991561
TI  - Marginalization among the marginalized: gay men's anti-effeminacy attitudes.
AB  - Contemporary research has shown that a significant portion of gay men have
      traits, interests, occupations, and behaviors that are consistent with the
      stereotype of gay men as effeminate, androgynous, or unmasculine. A great number
      of gay men exhibit gender nonconformity during childhood; most, however,
      "defeminize" during adolescence, possibly in response to stigmatization and
      society's gender-role prescription. Only a relatively small percentage of gay men
      continue to be gender-nonconforming in their adulthood, often at a price, as they
      also tend to have lower psychological well-being. Although gay culture
      historically appreciated camp and drag, which subvert the gender-based power
      hierarchy and celebrate gender nonconformity, anti-effeminacy prejudice is
      widespread among gay men. Ironically, gender-nonconforming gay men may suffer
      from discrimination not only from society at large, but from other gay men, who
      are most likely to have experienced stigmatization and may have been effeminate
      earlier in their lives. Drawing from anecdotes and findings from various sources,
      this article suggests that beyond many gay men's erotic preference for
      masculinity lies contempt and hostility toward effeminacy and effeminate men on
      sociopolitical and personal levels. Two correlates of gay men's anti-effeminacy
      attitudes are proposed: (a) hegemonic masculinity ideology, or the degree to
      which one subscribes to the value system in which masculinity is an asset, and
      men and masculinity are considered superior to women and femininity; and (b)
      masculinity consciousness, or the saliency of masculinity in one's self
      monitoring, public self-consciousness, and self-concept. These two variables are
      hypothesized to interact with gay men's self-perceived masculinity-femininity and
      their history of defeminization in predicting attitudes toward effeminacy.
      Research is underway to measure levels of anti-effeminacy attitudes and explore
      hypothesized correlates.

PMID- 11991562
TI  - Gays and lesbians in local races: a study of electoral viability.
AB  - Although lesbians and gays are more visible in the political arena than in the
      past, there is little published research on their electoral viability. This
      article helps to fill that void by presenting results of experimental research
      featuring respondents' reactions to a hypothetical candidate for a non-partisan
      city council seat. Sex and sexual orientation of the candidates were manipulated
      so that six categories were tested: a straight woman, a lesbian, a woman rumored
      to be lesbian, a straight man, a gay man, and a man rumored to be gay. The
      findings suggest that openly gay and lesbian candidates are seen as less viable
      than straight candidates or those rumored to be homosexual. Hence, the extent to
      which a candidate portrays his or her sexual orientation appears to make a
      difference in the chance to win elective office.

PMID- 11991563
TI  - The gay cousin: learning to accept gay rights.
AB  - In 1996-97 the author interviewed 73 civic leaders in Hamilton, Ontario, Canada,
      on their attitudes toward gay rights. Twelve respondents opposed gay rights, 40
      were moderately favorable to gay rights, and 21 were strongly favorable. Almost
      all favored basic equality rights (education, housing, employment), and only 10
      said they had difficulty with gay sexuality. Twenty-seven volunteered a concern
      with gay "flaunting," but this did not mean that they necessarily opposed gay
      rights. Respondents had the most difficulty accepting the rights of gays to marry
      and to adopt children, although almost all of those who opposed gay marriages
      agreed with the idea of a legal domestic partnership. Most agreed that children
      should be taught about homosexuality in schools. These 73 civic leaders reflect
      the rapidly changing attitudes to gay rights in Canada as a whole. Their more
      favorable attitudes were often a consequence of learning that someone close to
      them was gay or lesbian. They also responded to changes in religious teaching.
      Most respondents, including recent immigrants, were influenced by the dominant
      Canadian values of equality, respect for privacy, and respect for diversity. In
      general, the process these civic leaders were undergoing was one of humanizing
      gays, no longer thinking of them as the Other. In their view, human rights for
      gays did not mean mere formal equality, but rather concern and respect for gays.

PMID- 11991564
TI  - Research and commentaries on Richard von Krafft-Ebing and Karl Heinrich Ulrichs.

PMID- 11991565
TI  - Male sex workers in three Australian cities: socio-demographic and sex work
      characteristics.
AB  - This article describes the socio-demographic and sex work characteristics of sex
      workers in Sydney, Melbourne, and Brisbane. A total of 185 male sex workers
      completed the questionnaire component of the study. The results of this study
      serve to debunk many of the myths surrounding the popular view of the male sex
      worker (MSW). The respondents in this study were on average 27 years old, and the
      majority had completed secondary education, with 30% having gained some form of
      tertiary qualification. Interestingly, those MSWs who had not completed secondary
      education were mostly street workers and were generally aged under 25 years. The
      majority of sex workers lived in rented accommodation, with only 6% reporting to
      be homeless. Half of all respondents identified as being "gay," 31% as "bisexual"
      and 5.5% as "straight." More than half of the respondents were in a permanent
      relationship. Only 7.3% of this group reported using heroin daily, although the
      majority consumed alcohol, tobacco, marijuana, and ecstasy. The majority of sex
      workers had been in the profession for less than six months, although some had
      been working in the industry for more than ten years. Most of the sex workers
      reported having taken an HIV test and a preference to offer safer sex. The
      article highlights ways in which the work context of MSW can be better understood
      and supported by education and public policy programs.

PMID- 11991566
TI  - Effects of social contact with homosexuals on heterosexual Turkish university
      students' attitudes towards homosexuality.
AB  - The purpose of the study was to investigate the effects of social interaction
      with homosexuals on attitudes toward homosexuality in a sample of heterosexual
      Turkish university students. Hudson and Ricketts' 25-item scale was translated
      from English into Turkish and used to measure students' attitudes toward
      homosexuality. Findings, in general, suggested that exposure to and contact with
      homosexuals resulted in more positive attitudes toward homosexuality. Performed
      factor analysis demonstrated that there were three factors for the scale. The
      factors were labelled as "Social interaction with homosexuals," "Probable family
      ties with homosexuals," and "Tendency to be a homosexual." Subjects' negative
      attitudes toward homosexuality increased on the last two factors, which were
      about having a homosexual child or sibling, and being comfortable with being
      attracted to a homosexual. Results were discussed in terms of prejudice and
      intergroup contact.

PMID- 11991567
TI  - An empirical analysis of stressors for gay men and lesbians.
AB  - This research describes the empirical classification of stressors for gay men and
      lesbians. Volunteer respondents were recruited through a free local gay and
      lesbian newspaper, through gay and lesbian student organizations nationwide,
      through gay and lesbian bookstores nationwide, and at a gay festival in St.
      Louis. Nine hundred seventy-nine (979) participants completed a 70-item measure
      with stressors that had been identified in previous qualitative research.
      Participants were asked to indicate the degree to which they had experienced
      stress associated with a variety of experiences. Participants also completed a
      measure of dysphoria (CES-D), responded about their degree of openness regarding
      sexual orientation, and provided information about their relationship status and
      involvement with gay groups and activities. Using confirmatory factor analysis, a
      six-factor model was predicted to account for the data. One-factor, six-factor,
      and ten-factor models were tested. The ten-factor model yielded the best fit with
      the data and accounted for 63.5% of the variance. The factor structure remained
      stable when gay men were compared to lesbians, when those endorsing a
      predominantly gay versus exclusively gay orientation were compared, and when
      those in a relationship were compared to those who were not in a relationship.
      Increased gay stress was associated with more dysphoria. Implications of these
      findings are discussed and directions for future research are considered.

PMID- 11991568
TI  - Gender violence: transgender experiences with violence and discrimination.
AB  - There is a pervasive pattern of discrimination and prejudice against
      transgendered people within society. Both economic discrimination and
      experiencing violence could be the result of a larger social climate that
      severely sanctions people for not conforming to society's norms concerning
      gender; as such, both would be strongly associated with each other.
      Questionnaires were distributed to people either through events or through
      volunteers, and made available upon the World Wide Web. A sample of 402 cases was
      collected over the span of 12 months (April 1996-April 1997). We found that over
      half the people within this sample experienced some form of harassment or
      violence within their lifetime, with a quarter experiencing a violent incident.
      Further investigation found that experiencing economic discrimination because one
      is transgendered had the strongest association with experiencing a transgender
      related violent incident. Economic discrimination was related to transgendered
      people's experience with violence. Therefore, both hate crimes legislation and
      employment protections are needed for transgendered individuals.

PMID- 11991569
TI  - Head-centred motion perception in the ageing visual system.
AB  - Stationary objects appear to move in the opposite direction to a pursuit eye
      movement (Filehne illusion) and moving objects appear slower when pursued (Aubert
      Fleischl phenomenon). Both illusions imply that extra-retinal, eye-velocity
      signals lead to lower estimates of speed than corresponding retinal motion
      signals. Intriguingly, the velocity (i.e. speed and direction) of the Filehne
      illusion depends on the age of the observer, especially for brief display
      durations (Wertheim and Bekkering, 1992). This suggests relative signal size
      changes as the visual system matures. To test the signal-size hypothesis, we
      compared the Filehne illusion and Aubert-Fleischl phenomenon in young and old
      observers using short and long display durations. The trends in the Filehne data
      were similar to those reported by Wertheim and Bekkering. However, we found no
      evidence for an effect of age or duration in the Aubert-Fleischl phenomenon. The
      differences between the two illusions could not be reconciled on the basis of
      actual eye movements made. The findings suggest a more complicated explanation of
      the combined influence of age and duration on head-centred motion perception than
      that described by the signal-size hypothesis.

PMID- 11991570
TI  - Independent control of acceleration and direction of the hand when hitting moving
      targets.
AB  - Human subjects were asked to hit moving targets as quickly as they could.
      Nevertheless the speed with which the subjects moved toward identical stimuli
      differed between trials. We examined whether the subjects compensated for a lower
      initial acceleration by aiming further ahead of the target. We found that the
      initial acceleration of the hand and its initial direction were hardly
      correlated. Thus subjects did not aim further ahead when they hit more slowly.
      This supports our earlier suggestion that the acceleration of the hand and the
      direction in which it moves are controlled separately.

PMID- 11991571
TI  - Binocular information in the control of prehensile movements in multiple-object
      scenes.
AB  - Recent evidence suggests that the visual control of prehension may be less
      dependent on binocular information than has previously been thought. Studies
      investigating this question, however, have generally only examined reaches to
      single objects presented in isolation, even though natural prehensile movements
      are typically directed at objects in cluttered scenes which contain many objects.
      The present study was designed, therefore, to assess the contribution of
      binocular information to the control of prehensile movements in multiple-object
      scenes. Subjects reached for and grasped objects presented either in isolation or
      in the presence of one, two or four additional 'flanking' objects, under
      binocular and monocular viewing conditions. So that the role of binocular
      information could be clearly determined, subjects made reaches both in the
      absence of a visible scene around the target objects (self-illuminated objects
      presented in the dark) and under normal ambient lighting conditions. Analysis of
      kinematic parameters indicated that the removal of binocular information did not
      significantly affect many of the major indices of the transport component,
      including peak wrist velocity. However, peak grip apertures increased and
      subjects spent more time in the final slow phase of movement, prior to grasping
      the object, during monocularly guided reaches. The dissociation between effects
      of binocular versus monocular viewing on transport and grasp parameters was
      observed irrespective of the presence of flanking objects. These results
      therefore further question the view that binocular vision is pre-eminent in the
      control of natural prehensile movements.

PMID- 11991572
TI  - Set-size effects for spatial frequency change and discrimination in multiple
      targets.
AB  - In visual search tasks with a near-threshold target amongst distracters, log
      detection thresholds rise in proportion to the log of the number of stimuli.
      Previous research has shown a very steep slope for this set-size effect where the
      target is a change in spatial frequency (SF) across an ISI, suggesting a low
      level explanation for 'change blindness (Wright et al., 2000). Here, we analyse
      stimulus and task variables in order to determine the contributions of stimulus
      detection and attention processes. Stimuli consisted of two 150 ms frames each
      containing 1 to 4 Gabor targets, with an ISI of 250 ms. In a 2AFC detection task
      with uniform distracters, slopes of 0.23-0.52 were found, in line with visual
      search results. 2AFC SF discrimination tasks gave slopes of 0.68, 0.69 with
      homogeneous distracters and 0.76-0.96 with inhomogeneous distracters, consistent
      with averaging of stimuli within a frame. If the distracters were also made to
      change across ISI, averaging was impossible, and focal attention was required to
      solve the discrimination. This always gave set-size slopes > 1. It is concluded
      that, under conditions where a stimulus array can be analysed globally, change
      detection performance is limited by signal detection mechanisms, rather than
      limited capacity attention or memory mechanisms. However, where this is
      prevented, for example by changing more than one item, limitations due to
      attention or memory produce an even steeper set-size effect.

PMID- 11991573
TI  - Motion perception and motion estimation by total-least squares.
AB  - A computational model of motion perception is proposed. The model, which is
      gradient-based, adheres to the neural constraint that transmitted signals are
      positive-valued functions by posing the estimation of image motion as a quadratic
      programming problem combined with total-least squares: a model that assumes that
      image signals are contaminated by noise in both the spatial and temporal
      dimensions. By shrinking motion estimates with a regularizer whose subtractive
      effect introduces a contrast dependent speed threshold into motion computations,
      it is shown that the total-least squares model when posed as a quadratic
      programming problem, is capable of explaining both increases and decreases in
      perceived speed as these effects were reported by Thompson (1982) to vary as a
      function of image contrast and temporal frequency. The correlation that exists
      between the model's contrast speed response and results reported from visual
      psychophysics is consistent with the view that the visual system assumes that
      image signals may be contaminated by noise in both the spatial and the temporal
      domain, and that visual motion is influenced by the consequence of these
      assumptions.

PMID- 11991574
TI  - Going round in circles: shape effects in the Ebbinghaus illusion.
AB  - The Ebbinghaus illusion has traditionally been considered as either a sensory or
      a cognitive illusion, or some combination of these two. Cognitive contrast
      explanations take support from the way the illusion varies with the degree of
      shape similarity between the test and inducing elements; we show, however, that
      contour interaction explanations may account for this result too. We therefore
      tested these alternative theories by measuring the illusion with different test
      shapes as well as different inducer shapes, in all combinations. We found that
      for angular or hexagonal test shapes there is no similarity effect, and for some
      shape combinations there is no significant illusion, in contradiction to both of
      the traditional hypotheses. Instead, we suggest that an integrated model of
      visual processing is needed to account for the illusion.

PMID- 11991576
TI  - The onset repulsion effect.
AB  - There have been many previous reports of mislocalization associated with moving
      objects (e.g. flash-lag effect, Frohlich effect, representational momentum).
      Across four experiments, a new form of mislocalization--the onset repulsion
      effect (ORE)--is explored in which the error is always back along the observed
      path of motion. That is, when observers are asked to localize both the initial
      onset and the final offset positions of a moving object, by far the largest and
      most systematic error they make is in placing the onset point too early along the
      correct path of motion. Errors orthogonal to the path of motion and errors in
      localizing the offset point are minimal by comparison. Errors are also very small
      when motion is implied rather than continuous. The ORE can be observed with and
      without fixation, and as with other mislocalization effects, shows some
      dependence on direction and velocity. As the most obvious prediction in these
      studies, based on previous reports of mislocalization and the known properties of
      the visual system, would be for forward rather than backward errors, discussion
      will focus on the type of mechanism that may have given rise to the observed
      pattern of results.

PMID- 11991575
TI  - Isotropic integration of binocular disparity and relative motion in the
      perception of three-dimensional shape.
AB  - Richards (1985) showed that veridical three-dimensional shape may be recovered
      from the integration of binocular disparity and retinal motion information, but
      proposed that this integration may only occur for horizontal retinal motion.
      Psychophysical evidence supporting the combination of stereo and motion
      information is limited to the case of horizontal motion (Johnston et al., 1994),
      and has been criticised on the grounds of potential object boundary cues to shape
      present in the stimuli. We investigated whether veridical shape can be recovered
      under more general conditions. Observers viewed cylinders that were defined by
      binocular disparity, two-frame motion or a combination of disparity and motion,
      presented at simulated distances of 30 cm, 90 cm or 150 cm. Horizontally and
      vertically oriented cylinders were rotated about vertical and horizontal axes.
      When rotation was about the cylinder's own axis, no boundary cues to shape were
      introduced. Settings were biased for the disparity and two-frame motion stimuli,
      while more veridical shape judgements were made under all conditions for combined
      cue stimuli. These results demonstrate that the improved perception of three
      dimensional shape in these stimuli is not a consequence of the presence of object
      boundary cues, and that the combination of disparity and motion is not restricted
      to horizontal image motion.

PMID- 11991577
TI  - Metallic tracheal stents: complications associated with long-term use in the
      upper airway.
AB  - The use of metallic airway stents for the treatment of benign airway stenosis is
      increasingly advocated; however, the long-term safety and efficacy of these
      devices has not been established. Three case studies involving late but
      significant proximal tracheal stent complications are reported: 1 related to
      proximal mechanical stent failure and 2 related to obstructing granulation tissue
      and stenosis at the proximal stent orifice. Placement of these stents in close
      proximity to the cricotracheal junction is thought to be primarily responsible
      for these complications as a result of the excess shearing forces created at the
      stent-mucosal interface by the differential motion of the stent relative to the
      rigid subglottic airway and the more distensible trachea. Although the use of
      metallic stents remains appropriate in cases in which there is a defined and
      relatively short-term end point for treatment, caution is urged in using them in
      the proximal trachea for long-term management of benign airway disease.

PMID- 11991578
TI  - Swallowing and sensation: evaluation of deglutition in the anesthetized larynx.
AB  - To better characterize the role of laryngeal sensory systems in swallowing, we
      assessed 5 healthy adult volunteers via functional endoscopic evaluation of
      swallowing before and after bilateral superior laryngeal nerve block. The
      volunteers were tested multiple times with both liquid and puree consistencies.
      Laryngeal anesthesia resulted in a significantly higher (p < .05) incidence of
      premature spillage, pharyngeal residual, and laryngeal penetration with all
      consistencies, and a higher incidence of tracheal aspiration with liquid.
      Aspiration of puree was increased, but the difference did not achieve
      significance. These results contrast with those achieved by others with topical
      anesthesia, which caused little impairment. Other afferent modalities besides
      light touch, interrupted by superior laryngeal nerve block but not by topical
      anesthesia, may account for the difference. It is likely that this study
      underestimates the severity of clinical disability from afferent deficits,
      because of the short duration of the experimental deficit and the lack of
      associated comorbidities in the subjects. These findings have implications for
      clinical sensory testing and sensate flap reconstruction of pharyngeal defects.

PMID- 11991579
TI  - Adenovirus-mediated ex vivo gene transfer of human vascular endothelial growth
      factor in a rabbit laryngotracheal reconstruction model.
AB  - Free autologous cartilage, which is used in laryngotracheal reconstruction (LTR),
      may undergo progressive necrosis as a result of delayed revascularization.
      Angiogenic growth factors, such as vascular endothelial growth factor (VEGF),
      promote angiogenesis in the ischemic environment. We studied the effect of ex
      vivo gene transfer of VEGF121 on cartilage angiogenesis and graft survival in a
      rabbit model of LTR. Sixty rabbits underwent LTR with auricular cartilage. The
      grafts were treated at 1 x 10(9) plaque-forming units with 1) VEGF121 (n = 20),
      2) LacZ reporter gene (n = 20), or 3) saline solution (n = 20). Graft
      neovascularization and survival were histologically assayed at 1 and 10 weeks.
      Angiogenesis was enhanced at both 1 and 10 weeks after treatment with VEGF121 as
      compared to controls (p < .001). No statistical improvement in graft survival was
      evident after treatment with VEGF121. Ex vivo gene transfer to cartilage may be a
      promising gene therapy strategy to enhance revascularization--and, potentially,
      cartilage survival--under the proper conditions.

PMID- 11991580
TI  - Genotypic and phenotypic expression of vocal fold polyps and Reinke's edema: a
      preliminary study.
AB  - Although a great deal of research exists regarding lamina propria composition, no
      report exists that relates gene expression in benign laryngeal lesions to
      phenotypic markers. In this study, messenger RNA profiles for extracellular
      matrix proteins--procollagen I, collagenase, elastase, fibronectin, fibromodulin,
      decorin, hyaluronic acid synthase 2, and hyaluronidase--were completed on 5
      polyps and 4 Reinke's edema specimens. These genotypic profiles were correlated
      to a videostroboscopic parameter of mucosal wave stiffness, which was used as a
      measurement of phenotypic expression. Polyps, characterized by stiffer mucosal
      waves, had higher levels of gene expression, whereas stiffer mucosal wave scores
      for Reinke's edema were associated with lower gene activity levels. This study
      supports the hypothesis that there is a relationship between genotypic expression
      found in polyps and Reinke's edema and phenotype as defined by a loss of or a
      decreased mucosal wave. The study also gives clues as to the proteins responsible
      for the phenotype.

PMID- 11991581
TI  - Transtracheal oxygen catheters in a pediatric population.
AB  - This is the first report to evaluate transtracheal oxygen catheter (TTOC) use in
      a pediatric patient series. Seven pediatric patients (4 boys and 3 girls)
      received TTOCs in 2 tertiary care medical centers. The medical indications
      included bronchopulmonary dysplasia in 4 patients and tracheomalacia in the other
      3. The average age at the time of placement was 22 months (range, 2 weeks to 37
      months). Catheter placement for 4 patients was through an open tracheotomy stoma.
      In 3, placement was through a percutaneous technique. The follow-up ranged from 2
      weeks to 5 years. There were no long-term complications. Transient needs for
      supplemental oxygen were all met by the TTOC system. In 4 patients, the catheter
      has been removed because of resolution of the supplemental oxygen requirements.
      Minor complications included skin site infection and mucus plugging. In 1
      patient, accidental dislodging of the catheter led to its replacement in the
      operating room. In 1 percutaneous placement, a pneumothorax occurred and resolved
      without any persistent morbidity. We conclude that transtracheal oxygen delivery
      can be a reasonable alternative to a nasal cannula or formal tracheotomy in
      selected pediatric patients in whom long-term oxygen delivery, but not an
      alternate airway, is required. In order to avoid complications, meticulous
      technique must be adhered to in using the percutaneous approach for placement.

PMID- 11991582
TI  - Analysis of local recurrence in patients with selected T1-3N0M0 squamous cell
      carcinoma of the true vocal cord managed with a platinum-based chemotherapy-alone
      regimen for cure.
AB  - Based on an inception cohort of 35 patients with T1-3N0M0 squamous cell carcinoma
      of the true vocal cord who had a complete clinical response after a platinum
      based induction chemotherapy regimen and a minimum of 3 years of follow-up, the
      current retrospective study documented the long-term results and consequences of
      local recurrence following the use of a platinum-based chemotherapy-alone regimen
      for cure. During the years 1985 to 1996, 231 patients with invasive squamous cell
      carcinoma of the true vocal cord classified as T1-3N0M0 were managed at our
      department with a platinum-based induction chemotherapy regimen. A complete
      clinical response was achieved in 77 patients. Thirty-five of the 77 patients
      with complete clinical response were managed at our institution with a platinum
      based chemotherapy-alone regimen. The statistical analysis of data on survival,
      local control, nodal control, distant metastasis, and metachronous second primary
      tumor incidence was based on the Kaplan-Meier product limit method. Univariate
      analysis was performed for potential statistical relation between local
      recurrence and various variables. The 3- and 5-year actuarial survival estimates
      were 91.4% and 88.6%, respectively. Overall, the causes of death were
      intercurrent disease in 6 patients and metachronous second primary tumor in 4
      patients. The 3- and 5-year actuarial local control estimate was 64.8%. No
      significant statistical relation could be demonstrated between the incidence for
      local recurrence and the variables under analysis. Salvage treatment in patients
      with local recurrence yielded a 100% local control rate and laryngeal
      preservation rate. The 3- and 5-year actuarial lymph node control estimate was
      97.1%. The 3- and 5-year actuarial estimate for patients with distant metastasis
      was 0%. The 5- and 10-year actuarial estimates for patients with metachronous
      second primary tumor were 9.7% and 28.1%, respectively. Although local recurrence
      was noted in almost a third of patients with complete clinical response who were
      managed with a platinum-based chemotherapy-alone regimen, it did not appear to be
      detrimental, as none of the patients who had local recurrence ultimately died
      from their disease or lost their larynx.

PMID- 11991583
TI  - Isolated sphenoid sinus disease: an analysis of 122 cases.
AB  - Isolated sphenoid sinus disease (ISSD) is a relatively uncommon disease. The
      present study is a retrospective review of 122 patients with ISSD who were
      treated at the Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital
      at Shanghai Medical University over a 25-year period. The diagnosis of ISSD was
      made on the basis of history and physical examination, signs and symptoms, nasal
      endoscopy, and computed tomography (CT) and magnetic resonance imaging (MRI). The
      final diagnosis of ISSD was confirmed by histopathologic and microbiological
      examinations of the surgical specimens. The pathological findings in this study
      included sphenoid cyst (47 cases), sphenoid sinusitis (31 cases), fungal disease
      (19 cases), inverted papilloma (4 cases), sphenochoanal polyp (1 case), foreign
      body (8 cases), malignant tumors (8 cases), and others (4 cases). The most common
      initial symptom was headache, followed in decreasing order by visual changes,
      cranial nerve palsies, and nasal symptoms. The more frequent use of routine CT
      and MRI scanning, as well as endoscopy, in the diagnosis of sinus disease has led
      to an increase in the early diagnosis of ISSD. The recent advances in endoscopic
      sphenoidotomy has allowed for relatively safe and immediate treatment of ISSD,
      preventing late extension into adjacent vital structures, which is commonly
      fatal. Endoscopic surgery also enables the surgeon to make a precise pathological
      diagnosis.

PMID- 11991584
TI  - Effect of chronic electrical stimulation of laryngeal muscle on voice.
AB  - Conventional surgical therapies for bilateral laryngeal paralysis sacrifice voice
      to enlarge the airway. Electrical pacing of the posterior cricoarytenoid (PCA)
      muscle to restore glottal opening and allow ventilation offers a new treatment
      approach. The purpose of this investigation was to determine whether long-term
      stimulation of the PCA muscle altered perceptual, acoustic, and aerodynamic
      parameters of voice. Two patients underwent implantation of a Medtronic Itrel II
      laryngeal pacemaker. Voice evaluation was performed before surgery and at monthly
      postoperative sessions with the pacemaker off. Months of PCA stimulation did not
      change perceptual descriptors of voice quality. Measures of fundamental frequency
      and intensity, upper and lower limits of the dynamic frequency and intensity
      range, and phonatory flow rates were largely unaltered. The results indicated
      that there was no effect of laryngeal pacing on voice.

PMID- 11991585
TI  - Airflow resistance of heat and moisture exchange filters with and without a
      tracheostoma valve.
AB  - Rehabilitation of laryngectomees has been furthered by the introduction of heat
      and moisture exchange (HME) filters, placed over a tracheostoma or on a
      tracheostoma valve (TSV). The airflow resistance of HME filters is an important
      factor with regard to the comfort of the patient. The goal of this study was to
      determine the airflow resistance (defined as the pressure drop over the device
      divided by the squared airflow through the device) of 4 commercially available
      HME filters with and without a TSV. The pressure drop over and the airflow
      through the devices were measured in vitro. Distinct differences among the
      devices were found. The mean airflow resistance of the HME filters ranged from
      135 to 346 Pa x s2/L2, that of TSVs was between 66 and 297 Pa x s2/L2, and that
      of the combination was between 263 and 454 Pa x s2/L2. The Stom-Vent 2 HME filter
      and the Adeva Window TSV with an Adeva filter had the lowest airflow resistance
      of the devices measured in this study.

PMID- 11991586
TI  - Primary parotid gland Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma with its primary manifestation in the parotid gland is an
      exceedingly rare entity and is not usually suspected in the initial evaluation of
      a parotid mass. Because it is not suspected, the results of fine-needle
      aspiration cytology are often misleading, and parotidectomy is needed for a
      definitive diagnosis. The most common subtype encountered is lymphocyte
      predominant. The prognosis is favorable; the 5-year survival rate exceeds 90%.
      Treatment consists of chemotherapy, radiotherapy, or both. A case of primary
      parotid gland Hodgkin's lymphoma is presented along with a review of the
      literature and a discussion of the evaluation and management of this rare entity.

PMID- 11991587
TI  - Limitations to mobilizing the intrapetrous carotid artery.
AB  - The irregular and complex osteology of the bony skull base houses the
      intrapetrous internal carotid artery (ICA), which represents a potential obstacle
      to the complete extirpation of benign skull base lesions. This 2-part study 1)
      investigated the cadaveric basis for the mobilization of the intrapetrous ICA and
      2) correlated the cadaveric anatomic findings with the authors' clinical
      experience. We conclude that the ICA can be mobilized relatively safely. The
      degree of mobility achieved directly relates to the surgical approach and
      exposure. Limited mobility is achieved when an anterior petrosal approach is used
      with various neurosurgical procedures. Conversely, transcochlear and
      infratemporal approaches allow for optimal ICA translation. The safety of ICA
      mobilization is documented by the low complication rate in our series.

PMID- 11991588
TI  - Effects of frequency, instrumental family, and cochlear implant type on timbre
      recognition and appraisal.
AB  - The purpose of this study was to compare postlingually deafened cochlear implant
      recipients and normal-hearing adults on timbre (tone quality) recognition and
      appraisal of 8 musical instruments representing 3 frequency ranges and 4
      instrumental families. The implant recipients were significantly less accurate
      than the normal-hearing adults on timbre recognition. The implant recipients gave
      significantly poorer ratings than did the normal-hearing adults to those
      instruments played in the higher frequency range and to those from the string
      family. The timbre measures were weakly correlated with speech perception
      measures, but were significantly correlated with 3 cognitive measures of
      sequential processing.

PMID- 11991589
TI  - Incidence of regeneration of the chorda tympani nerve after middle ear surgery.
AB  - We retrospectively reviewed 52 patients who underwent middle ear surgery during
      which the chorda tympani nerves were severed and who then underwent secondary
      surgery 1 to 5 years later. In 22 patients (42.3%), regenerated chorda tympani
      nerves (entire length of the tympanic segment) were detected in the submucosal
      layer of the reconstructed eardrum during the secondary surgery. Before the
      secondary surgery, 16 patients (30.8%) showed threshold recovery on
      electrogustometry. When 5 regenerated nerves were observed by transmission
      electron microscopy, myelinated nerve fibers were detected in a small fascicle or
      connective tissue, but the number of myelinated axons was significantly decreased
      (7.4% to 84.6%; p = .01) compared with that in normal subjects (1,911 +/- 324; n
      = 4). There was a significant difference in the incidence of regeneration between
      the group with end-to-end anastomosis (5/5 or 100%) and that with nerve gap
      defects (17/47 or 36.2%; p <.05); this finding suggests that repair of the
      sectioned nerve produces a better incidence of regeneration than leaving the
      nerve unrepaired.

PMID- 11991590
TI  - Cartilage interposition in ossiculoplasty with hydroxylapatite prostheses: a
      histopathologic study in the guinea pig.
AB  - In this experimental animal study, a cartilage disk was interposed between a
      synthetic middle ear prosthesis and the tympanic membrane in guinea pigs to
      investigate its effect on the extrusion process of the implant. Two groups of
      guinea pigs were studied. One group consisted of animals in which the prosthesis
      was directly in contact with the tympanic membrane, and the other group consisted
      of animals in which a cartilage disk had been inserted between the head of the
      prosthesis and the tympanic membrane. Before histologic processing, in situ
      inspection was performed with an operating microscope. After fixation and
      embedding, light microscopic and transmission electron microscopic examination
      were performed. We studied the histopathologic aspects of the tympanic membrane
      with regard to the protrusion and extrusion processes of the middle ear implant.
      In this experimental model, protrusion and extrusion of a hydroxylapatite middle
      ear prosthesis was greatly reduced by interposition of a cartilage disk. Further
      clinical evaluation of these experimental results is needed in the human middle
      ear.

PMID- 11991591
TI  - Averaged electrode voltages in users of the Clarion cochlear implant device.
AB  - Averaged electrode voltages (AEVs) are of secondary importance for integrity
      testing of cochlear implant devices featuring back-telemetry. However, AEVs are
      device-independent and may show intermittent failures and deviant stimulation
      patterns unnoticed by telemetry. We collected AEVs from 18 users of the Clarion
      1.2 system and 6 users of the HiFocus system in order to establish norms for
      evaluating AEVs in difficult cases. The stimuli were presented with the standard
      clinical software. Monopolar stimulation at about 16 microA showed large AEVs
      (mean, 173 microV) suitable for integrity testing. No electrode failures were
      found. The AEV amplitudes from neighboring electrodes differed by less than 30%
      (2 SD). The AEVs from subjects with the Clarion HiFocus electrode and/or the
      Clarion electrode positioner were within the normal range. The AEV amplitudes
      from bipolar stimulation were much more variable. Inversion of phases between
      electrodes was found in patients with an altered state of the cochlea
      (otosclerosis and osteogenesis imperfecta) and in a patient with a curled
      electrode tip. There was no correlation across subjects between AEVs and
      electrode impedances. Therefore, impedances are dominated by the electrode-tissue
      interface, in contrast to AEVs, which are determined by the volume conduction in
      the body.

PMID- 11991592
TI  - Does endogenous or exogenous adenosine facilitate the functional recovery of the
      cochlea after ischemia?
AB  - The present study was undertaken to determine whether adenosine attenuates
      cochlear dysfunction induced by transient ischemia. Adenosine or erythro-9-(2
      hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, was
      administered by perilymphatic perfusion to albino guinea pigs that were subjected
      to cochlear ischemic episodes of 30-minute duration. The threshold shift of the
      compound action potential (CAP) from the preischemic value was significantly
      reduced in the animals perfused with EHNA 1 hour after the onset of reperfusion.
      However, perfusion of adenosine at concentrations of 100 micromol/L to 10 mmol/L
      did not reduce the postischemic CAP threshold shift by either 1 hour or 4 hours
      after the onset of reperfusion. These results suggest that the elevation of the
      adenosine concentration did not exert a protective effect on the cochlear
      ischemia-reperfusion injury, and that the protective action of EHNA is unrelated
      to elevating the adenosine concentration.

PMID- 11991593
TI  - Quality of life in a US national sample of adults with diabetes and motility
      related upper gastrointestinal symptoms.
AB  - Our objective was to describe the health-related quality of life (HRQoL) of
      individuals with diabetes with and without motility-related upper
      gastrointestinal symptoms compared to individuals without diabetes. A total of
      483 individuals with diabetes and 422 age- and gender-matched nondiabetic
      controls were recruited from a prior US national health survey for a telephone
      interview on upper gastrointestinal symptoms. Individuals with diabetes self
      reported a physician's diagnosis of diabetes and provided confirming information
      on clinical management measures. Subjects were asked about upper gastrointestinal
      symptoms in the month before interview using an instrument with demonstrated high
      reliability. HRQoL was measured using the SF-12 Health Survey. Individuals with
      diabetes reporting upper gastrointestinal symptoms scored significantly lower in
      HRQoL measures of physical health and mental health than either individuals with
      diabetes who did not report upper gastrointestinal symptoms or individuals
      without diabetes (P < 0.0001). Individuals with diabetes and no upper
      gastrointestinal symptoms had physical and mental health summary scores similar
      to those of individuals without diabetes. Early satiety was the strongest
      predictor (P < 0.0001) of differences in physical health scores between
      individuals with and without diabetes. Nausea was the strongest predictor (P <
      0.0001) of differences in mental health scores between individuals with and
      without diabetes. In conclusion, this is the first US national survey to
      demonstrate that motility-related upper gastrointestinal symptoms are associated
      with a significantly lower quality of life in individuals with diabetes.

PMID- 11991594
TI  - Characterization of gastric myoelectrical rhythms in patients with systemic
      sclerosis using multichannel surface electrogastrography.
AB  - The aim of this study was to characterize multichannel surface
      electrogastrography (EGG) recordings in patients with systemic sclerosis
      (scleroderma, SSc) compared to normal controls. Ten SSc patients and 13 healthy
      age-matched controls were enrolled in this study. Gastric myoelectrical activity
      was recorded using a four-channel electrogastrograph with abdominal surface
      electrodes. The EGG was recorded in the morning for 1 hr in the fasting state,
      and 1 hr after a standardized (500 kcal) test meal. It was found that: (1) The
      regularity of the gastric slow wave was significantly lower in the SSc patients
      when compared with the normal controls in both fasting and fed states. (2) There
      was a significantly higher incidence of bradygastria in the SSc patients. (3) The
      SSc patients showed a significantly lower percentage of slow wave coupling among
      the four-channel EGGs than the controls. (4) In comparison with the controls, the
      patients showed an impaired spatial distribution of gastric slow wave power in
      both fasting and fed states and an impaired spatial distribution of slow wave
      frequency in the fasting state. It was concluded that SSc patients have an
      abnormal gastric slow wave as shown in the multichannel EGG as a decreased
      percentage of normal slow waves and impaired spatial coordination of gastric slow
      waves. The multichannel EGG may serve as a simple, noninvasive, and cost
      effective method to assess gastric motility disorders and their relevance in
      patients with SSc.

PMID- 11991595
TI  - Electrogastrography in children with cystic fibrosis.
AB  - Patients with cystic fibrosis often develop upper gastrointestinal symptoms,
      which may be due to abnormal gastric motor function. The aim of the study is to
      determine the characteristics of gastric electrical activity in patients with
      cystic fibrosis and to compare electrogastrography patterns in symptomatic and
      asymptomatic patients. Electrogastrography was recorded in 14 symptomatic and 8
      asymptomatic children with CF. Both 30-min baseline and 30-min postprandial
      recordings was obtained. Dominant frequency cycles per minute, rhythm index, and
      power in decibels were obtained for the fasting and postprandial periods. The
      percentage of normal gastric waves was not affected by the meal and was
      significantly low in symptomatic and asymptomatic cystic fibrosis patients.
      Tachygastria was the most frequent dysrhythmia in both groups. Decreased
      postprandial power was seen in three symptomatic patients and one patient had no
      change. The percentage of normal gastric slow waves was low in symptomatic and
      asymptomatic cystic fibrosis patients. Tachygastria was the most frequent
      dysrhythmia. Decreased postprandial power was seen only in symptomatic patients.

PMID- 11991596
TI  - Helicobacter pylori infection is not associated with delayed gastric emptying or
      upper gastrointestinal symptoms in diabetes mellitus.
AB  - This study evaluated the relationship between gastric emptying and upper
      gastrointestinal symptoms with H. pylori status in patients with diabetes
      mellitus. Sixty-three outpatients (44 type 1, 19 type 2, age 45 +/- 1.5 years)
      underwent measurements of gastric emptying of a mixed solid and liquid meal,
      gastrointestinal symptoms (gastric and esophageal), glycemic control (HbA1c), and
      autonomic nerve function. Anti-H. pylori IgG antibodies were quantified using a
      validated kit. Gastric emptying of solid and/or liquid was delayed in 47 (75%)
      patients, and 31 (49%) had autonomic neuropathy. Fifteen (24%) of the patients
      were H. pylori positive. There were no differences in gastric emptying (solid
      retention at 100 min: 67.5 +/- 5.7% vs 63.2 +/- 3.6%; P = 0.63, liquid T50: 35.5
      +/- 2.9 min vs 42.5 +/- 3.4 min; P = 0.42), upper gastrointestinal symptoms
      (gastric 3.9 +/- 0.7 vs 4.0 +/- 0.4; P = 0.94 or esophageal 1.7 +/- 0.5 vs 1.3 +/
      0.2; P = 0.42) or HbA1c (8.8 +/- 0.4% vs 8.6 +/- 0.2%; P = 0.89) between H.
      pylori-positive and -negative patients. We conclude that H. pylori infection is
      not associated with delayed gastric emptying or upper gastrointestinal symptoms
      in diabetes.

PMID- 11991597
TI  - Diabetes mellitus may be associated with hepatocarcinogenesis in patients with
      chronic hepatitis C.
AB  - It is unknown whether diabetes mellitus is a risk factor of the
      hepatocarcinogenesis in patients with chronic hepatitis C. Three hundred eleven
      anti-hepatitis C virus (HCV) -positive patients who had undergone liver biopsies
      were studied. Patients with histologically proven cirrhosis or withdrawing within
      12 months were excluded. Thus, the remaining 279 patients were followed-up for
      65.9 +/- 29.4 months until the occurrence of hepatocellular carcinoma (HCC).
      During the observation period, HCC developed in 13 patients. Diabetes, age, sex,
      habitual alcohol intake, history of blood transfusion, serum alpha-fetoprotein
      level, histological findings, HCV genotype, viral load, and interferon therapy
      were assessed as potential risk factors. The Cox proportional hazard model
      identified that diabetes mellitus, histological staging, and age were
      independently associated with the occurrence of HCC. With multivariate analysis,
      only diabetes mellitus and age were associated with the occurrence of HCC.
      Diabetes mellitus may be associated with hepatocarcinogenesis in patients with
      chronic hepatitis C.

PMID- 11991598
TI  - p73 overexpression and nuclear accumulation in hepatitis C virus-associated
      hepatocellular carcinoma.
AB  - p73 is the first identified homolog of p53, but its function has not been
      established. Our study investigated the expression of p73 in liver tissue of
      patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC).
      RT-PCR was performed on RNA extracted from tumorous and nontumorous liver tissue
      of HCV-associated HCC, and control tissue and the cDNA were sequenced. Anti-p73
      polyclonal antibodies were used for protein analysis and immunohistochemistry,
      and patients' sera were analyzed for anti-p73 antibodies by radioimmunoassay.
      Analysis of the p53 gene was performed by SSCP and RFLP-PCR. The p73 mRNA and
      protein were highly expressed and accumulated in HCC tissues. Immunohistochemical
      studies revealed significant immunoreactivity in the nuclei of HCC cells. No
      mutations were detected in the p73 gene or in p53, and no loss of heterozygosity
      of the p53 gene was found. Anti-p73 antibodies were detected in sera of HCC
      patients, but were not significantly different from that occurring in non-HCV or
      non-HCC patients. In conclusion, p73 protein is overexpressed and accumulates in
      the nuclei of HCV-associated HCCs and may play a role in HCC development.

PMID- 11991599
TI  - Clinical predictors of large esophagogastric varices in patients with
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide,
      especially in Asia. Gastrointestinal bleeding due to esophagogastric variceal
      hemorrhage is one of the leading causes of death in HCC patients. The aim of
      study was to determine whether clinical variables were predictive of the presence
      of large esophagogastric varices (EGV) before performing endoscopy. Three hundred
      and four HCC patients who received endoscopy were enrolled and studied
      retrospectively. Univariate and stepwise logistic regression analysis were used
      to evaluate associations between the presence of large EGV and patient
      characteristics. There were 248 patients with small or no EGV and 56 patients
      with large EGV. The optimal critical values determined by a receiver operating
      characteristic curve for platelet count and albumin level were 135,000/mm3 and
      3.5 g/dl, respectively. Stepwise logistic regression analysis demonstrated that
      splenomegaly [odds ratio (OR): 9.72; confidence interval (CI): 3.75-25.17],
      portal vein thrombosis (OR: 2.73; CI: 1.50-4.97), low platelet count
      (<135,000/mm3) (OR: 3.78; CI: 2.07-6.90) and low albumin level (<3.5 g/dl) (OR:
      3.44; CI: 1.73-6.82) were significant, independent predictors for large EGV.
      Large EGV also could be independently predicted by Child-Pugh classification,
      splenomegaly (OR: 4.93; CI: 1.87-13.01), or portal vein thrombosis (OR: 2.37; CI:
      1.28-4.39) while excluding the non-cirrhotic patients. In conclusion,
      splenomegaly, low platelet count (<135,000/mm3), and low albumin level (<3.5
      g/dl) are clinical predictors to stratify HCC patients at risk of developing
      large EGV. Besides factors related to liver cirrhosis, portal vein thrombosis is
      also an important predictor for HCC patients with large EGV.

PMID- 11991600
TI  - Light chain deposition disease of the liver without renal involvement in a
      patient with multiple myeloma related to liver failure and rapid fatal outcome.
AB  - We describe a 36-year-old man with advanced multiple myeloma (Salmon and Durie
      stage III) who developed jaundice and severe cholestasis after a first cure with
      systemic chemotherapy of vincristine, doxorubicin, and oral dexamethasone (VAD).
      Serology for hepatitis A, B, and C and for CMV was negative. A liver ultrasound
      and CT scan showed mild hepatomegaly without evidence of extrahepatic or
      intrahepatic biliary tree dilatation. A percutaneous liver biopsy revealed
      perisinusoidal deposits of an abundant slightly eosinophilic, PAS-positive
      amorphous substance. Immunohistochemistry showed positivity for kappa-light
      chains and was negative for lambda-light chains, for IgA, IgG, IgM, and IgD
      immunoglobulins as well as for AA and AL proteins and for amyloid P component. A
      diagnosis of light chain deposition disease (LCDD) of the liver was made. The
      patient developed rapid deterioration of liver function, leading to a multisystem
      dysfunction and death. The occurrence of LCDD in multiple myeloma is close to 5%
      and myeloma is the underlying disease in two thirds of patients with LCDD. The
      kidneys are involved in almost all cases of LCDD and renal dysfunction usually
      reveals the disease. Only three patients with LCDD of the liver without overt
      renal involvement have been reported so far. This is the first observation of
      LCDD presenting with jaundice and severe cholestasis shortly after the diagnosis
      of high tumor mass myeloma, without overt renal involvement, leading rapidly to
      the patient's death.

PMID- 11991601
TI  - Unchanging trend of adenocarcinoma of the esophagus and gastric cardia in Taiwan:
      a 15-year experience in a single center.
AB  - Chronic gastroesophageal reflux disease is closely associated with esophageal
      adenocarcinoma and gastric cardia carcinoma, and esophageal adenocarcinoma and
      gastric cardia carcinoma have both been increasing in Western countries recently.
      Gastroesophageal reflux disease is not rare in Taiwan, but the frequency of
      occurrence of esophageal adenocarcinoma or gastric cardia carcinoma has not been
      studied here to date. Patients diagnosed with esophageal and gastric cancers at
      this hospital between 1981 and 1995 were recruited using the hospital tumor
      registry database. There were 45, 1546, 970, and 4167 patients diagnosed with
      esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cardia
      carcinoma, and gastric noncardia adenocarcinoma, respectively. The ratios of
      esophageal adenocarcinoma versus esophageal squamous cell carcinoma among the
      three cohorts were 0.030, 0.016, and 0.041, respectively (trend, P = 0.086). The
      corresponding values for gastric cardia carcinoma versus gastric noncardia
      adenocarcinoma were 0.252, 0.232, and 0.218, respectively (trend, P = 0.256). The
      ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma and
      of gastric cardia carcinoma versus gastric noncardia adenocarcinoma have not
      risen in the three cohorts. Unlike the situation in Western countries, the
      incidence of esophageal adenocarcinoma and gastric cardia carcinoma versus
      esophageal squamous cell carcinoma and gastric noncardia adenocarcinoma have not
      increased over the past 15 years among the Chinese in Taiwan. Although
      gastroesophageal reflux disease is common here, its definite pathogenesis leading
      to esophageal adenocarcinoma or gastric cardia carcinoma remains unresolved.

PMID- 11991602
TI  - Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi
      motility.
AB  - Gabexate mesilate is an antiprotease drug, which reduced the severity of
      pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits
      sphincter of Oddi motility but no data are available in humans. The aim of this
      study was to verify by manometry the action of gabexate on human sphincter of
      Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis
      (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic
      sphincter of Oddi manometry was done in basal conditions and during infusion of
      gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic
      contractions, and motility index (amplitude per frequency) were calculated before
      and after gabexate injection. Statistical analysis was performed by using
      Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of
      stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic
      activity was not evaluable in five patients with stenosis. Basal pressure was
      unaffected by drug infusion, while gabexate caused a significant reduction of
      phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05)
      and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility
      index was reduced on average by 49%. In conclusion, this pilot study confirms, in
      patients with acute recurrent pancreatitis, the inhibitory action of gabexate on
      sphincter of Oddi motility already described in dogs. This action needs to be
      revaluated at therapeutic dosages. On the other hand, prophylactic use of the
      drug should be avoided during sphincter of Oddi manometry, in order to avoid
      false negative results.

PMID- 11991603
TI  - Pulmonary hemodynamics and gas exchange after liver transplantation in patients
      with cirrhosis.
AB  - In patients with cirrhosis, discrepant findings have been reported on the
      evolution of pulmonary hemodynamics and gas exchange after liver transplantation.
      The aim of this study was to evaluate the effects of liver transplantation on
      pulmonary and systemic hemodynamics and gas exchange in patients transplanted for
      cirrhosis. Forty-three patients with cirrhosis underwent hemodynamic
      investigations before and one year after liver transplantation. Mean pulmonary
      arterial pressures did not significantly change after transplantation (from 17 +/
      4 to 17 +/- 3 mm Hg) whereas pulmonary vascular resistance significantly
      increased by 62%. Cardiac index significantly decreased by 20%. PaO2 did not
      change significantly after transplantation (from 88.8 +/- 13.9 to 88.5 +/- 12.1
      mm Hg) and PaCO2 significantly increased by 16%. In conclusion, liver
      transplantation has no effect on pulmonary pressures but normalizes pulmonary
      vascular resistance in patients with cirrhosis without pulmonary hypertension.
      Moreover, it has no major effect on gas exchange in patients with cirrhosis
      without hypoxemia.

PMID- 11991604
TI  - Five cases of fulminant hepatitis due to herpes simplex virus in adults.
AB  - Five cases of fulminant hepatitis due to herpes simplex virus were identified
      among patients admitted to the Thomas E. Starzl Transplantation Institute between
      January 1991 and September 1994. The diagnosis was established in three of the
      five patients on the basis of transjugular liver biopsy specimen results. These
      three patients were treated with acyclovir; two survived and one required liver
      transplantation. Early histologic diagnosis, specific antiviral treatment, and
      liver transplantation in selected patients may improve the clinical outcome of
      this almost uniformly fatal disease.

PMID- 11991605
TI  - Anti-ENA antibodies in patients with chronic hepatitis C virus infection.
AB  - The aim of the study was to assess the prevalence of anti-extractable nuclear
      antigen (ENA) antibodies in patients with chronic HCV infection. We studied 69
      consecutive patients with chronic hepatitis C, 59 control subjects with non-HCV
      liver diseases, and 22 control subjects with extrahepatic, non-immune-mediated,
      chronic diseases. Thirty-two (46.3%) of 69 patients with HCV infection had anti
      ENA antibodies: 16 (23.1%) showed anti-SSA antibodies and 14 (20.2%) had anti-SSB
      antibodies. Four of the patients with HCV infection suffered from sicca syndrome
      and three of them had also anti ENA antibodies. The prevalence of anti-ENA
      antibodies was significantly higher in the anti-HCV subjects compared with both
      control groups. Twenty-six of 44 HCV-antibodies-positive females had anti-ENA
      antibodies, compared with 6 of 25 males, showing a sex related difference. In
      conclusion, our results outline a specific role of HCV infection in the induction
      of anti-ENA antibodies. Female sex seems a predisposing condition.

PMID- 11991606
TI  - IgA against gut-derived endotoxins: does it contribute to suppression of hepatic
      inflammation in alcohol-induced liver disease?
AB  - Endotoxins of intestinal origin are supposed to play an important role in the
      development of alcoholic hepatitis in man. To estimate the role of immunoglobulin
      response to gut-derived endotoxin in the development of alcohol-induced liver
      disease, serum levels of IgA and IgG against fecal endotoxin, endotoxin, and
      acute-phase proteins were measured in patients with different stages of alcoholic
      liver disease and in healthy controls. Antibodies of type IgA, but not IgG,
      against fecal endotoxins were significantly increased in patients with alcohol
      induced liver disease. IgA antibodies against fecal endotoxin were found to be
      closely correlated with the plasma concentrations of alanine aminotransferase,
      gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic
      liver disease. In conclusion, as IgA located in body tissue was shown to suppress
      the inflammatory process, enhanced production of IgA against endotoxin of
      intestinal origin may contribute to inactivation of this compound, thereby
      reducing its damaging effect on the liver.

PMID- 11991607
TI  - Liver development in a rat model of fetal alcohol syndrome.
AB  - The inhibitory effects of alcohol on hepatic growth in adults raises the
      possibility that the liver may be involved in fetal alcohol syndrome (FAS) in
      infants. To test this hypothesis, pregnant Sprague-Dawley rats were fed liquid
      diets containing either ethanol as 36% of the total calories, or were allowed ad
      libitum feeding of a control liquid diet (controls) throughout pregnancy. Other
      dams were exposed to the ethanol diet only during the first or last half of
      pregnancy. Pups delivered of dams exposed to the various diets (N = 40-45/group)
      were killed at 1, 3, 7, and 14 days of age. In addition to brain weights, crown
      rump lengths, and facial features, the following parameters of liver development
      were documented; liver weight, liver/body weight ratio, liver histology, hepatic
      ornithine decarboxylase activity (ODC), hepatic protein content, and rate of
      hepatic DNA synthesis (as determined by [3H]thymidine incorporation). The results
      revealed that pups exposed to ethanol throughout pregnancy but not ad libitum
      control diet pups had brain weights, crown-rump lengths, and facial features in
      keeping with FAS. With respect to liver development, the livers in FAS pups were
      consistently smaller than in the control group. However, total body weights were
      decreased to a greater extent, such that when corrected for body weights, the
      smaller livers in FAS pups only became significant on day 14 of life. Liver
      histology was similar in the two groups with no signs of active inflammation or
      fibrosis. Hepatic ODC activity was also similar, indicating no impairment in
      polyamine synthesis. Hepatic DNA synthesis rates were decreased in FAS pups at
      all time intervals. Pups delivered of dams exposed to ethanol during either the
      first or last half of pregnancy had results comparable to those of controls. To
      identify the mechanism(s) responsible for these findings, a second series of
      experiments was performed wherein the hepatic expression of the following factors
      associated with liver development were documented by northern-blot analyses;
      growth hormone receptor (GHr), insulin-like growth factor-I (IGF-I) and -II (IGF
      II) and IGF binding proteins (IGFBPs) 1, 2, 3, and 4 mRNA on gestational days 16
      and 20 and postpartum days 1 and 7. In this series, a third group of pups derived
      from dams in whom caloric consumption was matched to that of the ethanol-fed dams
      (isocaloric controls) were also studied. The results revealed no consistent
      differences in GHr, IGF, or IGFBP mRNA expression in the three groups. In
      conclusion, liver development and hepatic DNA synthesis were significantly
      impaired in this animal model of FAS. That impairment, however, was not
      associated with decreases in either polyamine synthesis or disturbances in the
      hepatic component of the GH/IGF/IGFBP axis.

PMID- 11991608
TI  - Hyperendothelinemia and ICG clearance in alcoholic and nonalcoholic cirrhosis.
AB  - Plasma endothelin (ET) levels are generally increased in cirrhosis patients in
      line with the severity of disease; however, the pathophysiological significance
      remains to be clarified. We evaluated the plasma ET levels in 49 patients with
      alcoholic cirrhosis and in 53 patients with nonalcoholic cirrhosis of the same
      disease severity. The plasma ET level was significantly elevated in alcoholic
      patients (P < 0.0001) and slightly so in nonalcoholic patients (P < 0.01); the
      difference was significant between the groups (P < 0.0001). The plasma ET level
      was positively correlated with the Child-Pugh score (P < 0.0001) and negatively
      correlated with prothrombin index (P < 0.001) and indocyanine green (ICG)
      clearance (P < 0.0001). The plasma ET level decreased 32% in alcoholic patients
      after abstinence (P < 0.001), but remained correlated with ICG clearance (P <
      0.001) and the Child-Pugh score (P < 0.01), but not with prothrombin index.
      Regression analysis revealed that the plasma ET level was correlated with
      estimated hepatic blood flow and alcohol abuse. These findings suggest that
      hyperendothelinemia in cirrhosis patients is related to alcohol abuse and disease
      severity, especially to impaired hepatic hemodynamics.

PMID- 11991609
TI  - Intracellular cytokine analysis of CD4-positive T cells predictive of sustained
      response to interferon therapy for patients with chronic hepatitis C.
AB  - We investigated whether the measurement of serum interleukin 18 (IL-18) and
      intracellular cytokine analysis of peripheral blood CD4-positive T cells (ICA
      CD4+ Tc) of chronic hepatitis C (CH-C) patients before and two weeks after
      interferon (IFN) administration are useful for predicting sustained response to
      IFN. Twenty-nine CH-C patients received IFN every day for two weeks and three
      times a week for 22 weeks. Patients were divided into two groups: responders, in
      whom serum HCV-RNA was undetectable at the end of the follow-up (week 48), and
      nonresponders, in whom any other patterns were seen. Before and two weeks after
      IFN administration, serum IL-18 and ICA-CD4+ Tc as described by Jung et al were
      measured. Serum IL-18 and the relative prevalence of IFN-gamma+ and IL-4+, IFN
      gamma+ and IL-4 (Th-1), and IFN-gamma- and IL-4+ cells in the responders were
      significantly increased, but only the relative prevalence of Th-1 cells in the
      nonresponders was increased two weeks after IFN therapy. In conclusion, ICA-CD4+
      Tc and the measurement of serum IL-18 might be useful for predicting IFN therapy
      by comparing the results between before and two weeks after IFN.

PMID- 11991610
TI  - Efficacy of daily induction dosing vs standard thrice weekly dosing of interferon
      alpha2B for initial treatment of chronic hepatitis C.
AB  - The aim of this study was to compare the effect on HCV RNA levels of using
      induction dosing with 5 MU interferon-alpha2b (IFN) given daily for four weeks
      followed by 5 MU IFN given three times a week (TIW) for 44 weeks vs standard
      noninduction TIW dosing of 5 MU IFN for 48 weeks. We randomly assigned 135
      patients with chronic hepatitis C to induction therapy or noninduction therapy.
      After four weeks of therapy 17/65 (26.1%) patients had undetectable HCV viral
      levels in the induction group compared with 16/64 (25.0%) patients in the
      noninduction group. The mean HCV viral levels were similar at four weeks in
      patients who received induction and noninduction therapy. Mean HCV viral titers
      in the induction group increased from 4 to 16 weeks, whereas the mean viral
      titers in the noninduction group decreased during this time (P < 0.0001). HCV RNA
      was undetectable at the end of therapy in 17/66 (25.8%) in the induction group
      and 21/68 (30.9%) in the noninduction group. The sustained virologic response
      rate 24 weeks after the end of therapy was 14/67 (20.9%) in the induction group
      compared with 13/68 (19.1%) in the noninduction group. These results indicate
      that an initial four week period of daily interferon confers no benefit in the
      treatment of patients with chronic hepatitis C.

PMID- 11991611
TI  - Beta-carotene-induced hepatic fibrosis.

PMID- 11991612
TI  - Sarcoidosis-associated hepatitis C virus infection.
AB  - Although several reports of sarcoidosis have been reported in hepatitis C virus
      (HCV)-infected patients treated with interferon-alpha, this association has never
      been described in nontreated HCV patients. We report two cases of sarcoidosis
      associated with chronic hepatitis C infection. The patients developed
      multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years
      after the presumed date of infection. One patient obtained remission of
      sarcoidosis with corticosteroid treatment but the other remained
      corticodependent. The levels of hepatic enzymes were not significantly modified
      throughout the course of corticosteroid therapy. In conclusion, these case
      reports suggest that HCV itself could induce a granulomatous reaction in chronic
      HCV-infected patients through the stimulation of the cellular immune system. It
      could be of interest to test for HCV infection all patients diagnosed with
      sarcoidosis and to watch over every treated or nontreated hepatitis C infected
      patient for the development of granulomatous lesions.

PMID- 11991613
TI  - A prospective study of dyspepsia in primary care.
AB  - Dyspepsia is a common complaint, but its course and associated resource
      utilization have not been well described. In this study, 288 adult, primary care
      patients with dyspepsia treated at ambulatory clinics were followed prospectively
      for one year. Medical chart, utilization, and baseline and one-year follow-up
      survey data were collected. These patients had 13.3 medical visits (sex- and age
      standardized) during the follow-up period, 55% above standardized mean visits for
      a comparison group of nondyspepsia patients. Standardized mean charges of $3542
      for dyspeptics was 126% above nondyspepsia patient charges. Over half had
      gastrointestinal-related follow-up visits; 61% used gastrointestinal drugs; and
      43% had gastrointestinal procedures. NSAID users had higher gastrointestinal
      related utilization than did nonusers, recording an additional gastrointestinal
      visit (P < 0.001) and $678 more in charges (P = 0.03). Eighty-six percent of the
      189 follow-up survey respondents experienced gastrointestinal symptoms at some
      time during the follow-up year. This study showed that most primary care
      dyspepsia patients remained symptomatic after one year and were intensive users
      of medical care.

PMID- 11991614
TI  - Delta13CO2 excretion and expression of dyspeptic symptoms in patients evaluated
      for Helicobacter pylori infection by [13C] urea breath test.
AB  - Previous studies showed that either the urease activity possessed by H. pylori
      and the bacterial load may influence the results of the [13C] urea breath test.
      However, the correlation between urease activity and dyspepsia is unclear. The
      aim of our study was to evaluate whether the urease activity of the
      gastroduodenal tract may influence the severity of dyspeptic symptoms. In all,
      2520 dyspeptic patients (1109 men, 1411 women; mean age 47 +/- 16 years) without
      gastroesophageal reflux disease, diabetes, vascular disorders, liver and biliary
      tract diseases, and tumors of the gastrointestinal tract and with a normal
      appearing abdominal ultrasonography were enrolled. All these patients underwent a
      [13C] urea breath test and filled out a questionnaire on dyspeptic symptoms.
      Subjects were divided in five different groups according to delta over baseline
      (DOB) values (group 1 < 3.5, group 2 = 3.5-6; group 3 = 6.1-11, group 4 = 11.1
      23, group 5 > 23.1). The prevalence and intensity of dyspeptic symptoms were
      compared among groups. In all, 1688 patients (67%, 928 females and 760 males;
      mean age 48 +/- 15 years) were H. pylori-positive. The chi-squared test and
      analysis of variance showed increase of frequency and intensity of each dyspeptic
      symptom according to DOB values. In conclusion, Dyspepsia may parallel gastric
      urease activity. However, whether higher DOB values are related to higher
      bacterial load or, alternatively, to the presence of particular H. pylori strains
      able to produce larger amounts of urease is uncertain.

PMID- 11991615
TI  - Helicobacter pylori and acetylsalicylic acid synergistically accelerate apoptosis
      via Fas antigen pathway in rabbit gastric epithelial cells.
AB  - The mechanism for gastric epithelial cellular apoptosis by both H. pylori and
      NSAIDs remains unknown. Normal gastric epithelial cells, collected from rabbit
      stomach, were cultured with viable H. pylori and/or an acetylsalicylic acid for
      24 hr as an in vitro model of gastric epithelial cell injury. The Fas antigen
      expression rate in the gastric epithelial cells was measured using a FACScan. In
      group E, in which H. pylori inoculation of epithelial cells was followed by
      treatment with an NSAID, the rate of Fas antigen expression was significantly
      higher than the rate observed after treatment with either H. pylori or NSAID
      alone. Despite the fact that drug treatment alone did not significantly increase
      the Fas expression rate vs control cells. The results suggest that H. pylori and
      NSAID induce gastric cell injury as apoptosis via the Fas antigen pathway in a
      synergistic manner and that this effect is particularly strong when NSAID
      treatment follows H. pylori infection.

PMID- 11991616
TI  - The role of Herpes simplex and Helicobacter pylori infection in the etiology of
      persistent or recurrent gastric erosions: a follow-up study.
AB  - The etiology of chronic gastric erosions is unknown. We have evaluated the
      significance of Helicobacter pylori and herpes simplex virus (HSV) infections,
      the use of nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, and smoking in
      a prospective long term follow-up study. A prospective series of 117 patients
      with gastric erosions and 117 controls were studied in 1974-1981, and invited for
      reendoscopy in 1996. At both visits, H. pylori infection was diagnosed by
      histology, serum HSV antibodies were measured, and the use of NSAIDs, alcohol,
      and smoking was evaluated by interview. Biopsies from erosions from the latter
      visit were studied for HSV by immunohistochemistry and polymerase chain reaction
      (PCR). In the follow-up visit, 16 of 42 patients had still gastric erosions while
      six of 47 controls had developed erosions. No HSV antigen or DNA could be
      detected in biopsy specimens. However, only high antibody titers (> or = 32)
      against HSV at the first visit predicted persistence of erosions (P = 0.000),
      while H. pylori infection, use of NSAIDs, alcohol, or smoking were not associated
      with chronic erosions. High HSV titers at the follow-up visit were also
      significantly associated with concurrent erosions in the patient group. In
      conclusion, the results suggest that a significant proportion of chronic gastric
      erosions are related to HSV infection.

PMID- 11991617
TI  - Cellular immune responses in Helicobacter heilmannii infection: evaluation of the
      role of the host and the bacterium.
AB  - We evaluated some aspects of the immune response to Helicobacter heilmannii in
      two mouse strains. Gastritis that was more severe in infected C57BL/6 mice. A
      proliferative response to H. pylori antigens was observed in splenocytes from H.
      heilmannii-positive and -negative mice, similar in the positive- and negative
      BALB/c mice, but lower in the positive- than in the negative-C57BL/6 animals. A
      decrease in B cells and an increase in CD4+ cells after stimulation with type I
      H. pylori antigen and an increase in CD8+ cells after stimulation with type I and
      II antigens was observed in infected C57BL/6 mice. Conversely, the percentage of
      CD4+, CD8+, and B cells was similar in positive- and negative-BALB/c mice. These
      results demonstrated that the immune response is similar in H. heilmannii and H.
      pylori infection and strengthened the importance of host and bacterial virulence
      markers in the immune response to gastric Helicobacter infections.

PMID- 11991618
TI  - Infection by CagA-positive Helicobacter pylori strains in patients with ischemic
      heart disease: prevalence and association with exercise-induced
      electrocardiographic abnormalities.
AB  - The role of H. pylori infection in increasing the risk of ischemic heart diseases
      (IHD) is still debated. We determined serologically the prevalence of overall H.
      pylori and CagA-positive H. pylori infection in 63 consecutive patients with IHD
      and 189 gender- and age-matched controls. We also determined in patients the
      influence of the infection and the CagA serological status on the results of an
      exercise ECG test and other parameters considered possible variables that may
      enhance the risk of IHD. The prevalence of H. pylori infection in patients and
      controls was 79.3% and 73.0%, respectively (P = 0.403) and that of CagA-positive
      H. pylori infection was 69.8% and 42.3%, respectively (P = 0.0002). The scores of
      the ECG S-T segment and T-wave abnormalities in the course of an exercise ECG in
      uninfected patients and in patients infected by CagA-negative and CagA-positive
      H. pylori strains were (mean +/- SD): 1.59 +/- 0.67, 1.92 +/- 0.64, and 2.19 +/-
      0.70, respectively; (P = 0.011, 95% confidence limits of difference 0.15-1.07,
      CagA-positive infected vs uninfected patients). There was no intergroup
      difference in the levels of peripheral white blood cells, glucose, cholesterol,
      triglycerides, creatinine, and systolic and diastolic pressure. In conclusion,
      genetic heterogeneity of H. pylori could possibly explain some conflicting
      results concerning the association of H. pylori infection with IHD. Coronary
      vessels of IHD patients infected by CagA-positive H. pylori strains may be
      damaged more severely than those of uninfected patients.

PMID- 11991619
TI  - Influence of Helicobacter pylori infection on healing and relapse of acetic acid
      ulcers in Mongolian gerbils.
AB  - Both Helicobacter pylori and NSAIDs play important roles in the healing and
      relapse of peptic ulcers in man. We examined how H. pylori infection,
      indomethacin, and their combination affects the healing of gastric ulcers and
      whether or not such factors provoke a relapse of healed gastric ulcers in
      Mongolian gerbils. Gastric ulcers were induced by serosal application of an
      acetic acid solution. H. pylori (ATCC43504) was orally administered once into
      animals with active and healed ulcers. Ulcers healed within eight weeks and
      remained healed for the following six months. H. pylori infection significantly
      delayed ulcer healing four weeks following infection. Indomethacin treatment
      showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected
      Mongolian gerbils was significantly delayed by indomethacin. H. pylori infection
      resulted in a relapse of healed ulcers from one to six months after infection,
      with a gradual increase in size. By the fourth month following a relapse, the
      serum gastrin level had significantly increased. H. pylori-induced ulcers in the
      posterior wall coexisted with relapsed ulcers in the anterior wall five and six
      months later. Omeprazole markedly prevented the ulcer relapse caused by H. pylori
      infection. It is concluded that, in Mongolian gerbils, H. pylori infection
      delayed the healing of preexisting gastric ulcers and resulted in the relapse of
      healed ulcers, yet indomethacin had little or no effect on ulcer healing or
      relapse.

PMID- 11991620
TI  - Antioxidant effect of T-type calcium channel blockers in gastric injury.
AB  - It is known that calcium ion has an important role in the cellular function. For
      this reason, calcium channel blockers may have a protective action against
      gastric injury which is induced by various stimuli. In this study, the influence
      of mibefradil on ethanol-induced gastric injury was investigated in rats.
      Mibefradil was given at a dose 50 mg/kg intraperitoneally 30 min before
      administration of 1 ml absolute ethanol given by gavage. We compared this effect
      of mibefradil with that of omeprazol. Ethanol-induced mucosal damage was
      evaluated using three different approaches: analysis of biochemical parameters
      and pathologic and macroscopic investigation. It was found that pretreatment with
      mibefradil significantly reduced ethanol-induced macroscopic, pathologic, and
      biochemical changes in the gastric mucosa. In conclusion, it is speculated that
      this findings may prove important in the development of new and improved
      therapies for the treatment and prevention of gastric ulcers in humans.

PMID- 11991621
TI  - Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its
      antioxidant effect.
AB  - Oxygen radical release has been proposed as a pathogenic factor of the ethanol
      induced acute gastric injury. Melatonin, a pineal hormone, is known to scavenge
      oxygen free radicals. We investigated whether parenteral administration of
      melatonin prevented ethanol-induced macroscopic damage, polymorphonuclear (PMN)
      leukocyte infiltration, depletion of total glutathione (tGSH) concentration, and
      glutathione reductase (GSSG-Rd) activity in the rat gastric mucosa. We compared
      the effects of melatonin with those of omeprazole. Ethanol-induced mucosal damage
      was evaluated using three different parameters: gastric total glutathione (tGSH)
      concentration and glutathione reductase (GSSG-Rd) activity, the number of PMN
      leukocytes, and macroscopic investigation. Gatric tGSH concentration and GSSG-Rd
      activity decreased and the number of PMNs increased after ethanol administration.
      It was found that pretreatment with melatonin increased both tGSH concentration
      and GSSG-Rd activity. Melatonin also reduced ethanol-induced PMN infiltration in
      the stomach. Ethanol administration damaged the entire gastric mucosa. Melatonin
      significantly decreased the extent of ethanol-induced macroscopic injury. In
      conclusion, these findings support the conclusion that the protection conferred
      by melatonin in gastric ulcer is presumably due to its antioxidant activity.

PMID- 11991622
TI  - Long-term rebamipide therapy improves Helicobacter pylori-associated chronic
      gastritis.
AB  - We investigated an antiinflammatory effect of rebamipide [2-(4
      chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid], a gastroprotective
      agent, in H. pylori-associated gastritis. Eighty-six patients with H. pylori
      positive chronic gastritis were enrolled: 53 were treated with rebamipide (300 mg
      daily for 12 months) and 33 served as controls. Significant decreases in
      mononuclear cell infiltration into the antrum and corpus were noted in the
      rebamipide treatment group (before vs after, 1.42 +/- 0.15 vs 1.02 +/- 0.15; P <
      0.01 and 1.60 +/- 0.15 vs 1.21 +/- 0.14; P < 0.05, respectively). Levels of
      infiltrating neutrophil were also decreased in the antrum (before vs after, 0.98
      +/- 0.14 vs 0.70 +/- 0.13; P < 0.05) and were associated with a decrease in iNOS
      production. Sera from patients treated with rebamipide showed a significant
      decrease in gastrin (276.3 +/- 58.3 pg/ml vs 173.0 +/- 34.2 pg/ml; P < 0.05),
      whereas no change was observed in the control group. These suggest that long-term
      rebamipide treatment improved histologic gastritis and decreased serum gastrin
      levels in H. pylori-associated gastritis.

PMID- 11991623
TI  - Stereologic characteristics of pig small intestine during normal development.
AB  - Stereologic methods were used to study the behavior of the pig's intestinal wall
      during periods that are characterized by a high incidence of gastrointestinal
      disorders. For this purpose conventionally stained transverse and vertical
      paraffin sections were made of the small intestine (duodenum, jejunum, and ileum)
      of fetal, neonatal, and weaned pigs. The volumes of the intestinal walls were
      estimated using Cavalieri's method. Subsequently, the surface density (Sv) of the
      tunica mucosa and the volume densities (Vv) of the different small intestinal
      elements were estimated. Finally, the surface and volumes per serosal surface
      area (Ss and Vs) were calculated. The decrease of Sv can be attributed to the
      finding that the mucosal surface increases to a lesser extent compared with the
      volume of the intestinal wall. The Vs of the various layers increased
      postnatally, illustrating that the intestinal wall thickens. Despite an
      increasing total mucosal surface, this postnatal thickening causes Ss to decline.
      Each of these changes is temporally related to dietary changes, an increased
      antigen load, and an increased need for protection. Additionally, the regional
      differences of the various parameters match the qualitative descriptions of the
      small intestine of the pig and relate to region-specific functions.

PMID- 11991624
TI  - Porcine ileitis model induced by TNBS-ethanol instillation.
AB  - Nine young pigs were used to evaluate the ability of an trinitrobenzene sulfonic
      acid-ethanol (TNBS-EtOH) mixture, in varying combinations, to induce ileitis
      comparable to that caused by intraintestinal instillation in other species. The
      distal ileum was accessed via laparotomy in anesthetized animals and the TNBS
      EtOH was instilled via hypodermic needle. In three pigs in which the instillate
      was not held within an ileal segment, there were no ileal lesions noted upon
      necropsy at two weeks after instillation. In all six pigs in which the instillate
      was confined to a 10-cm length of distal ileum for 10-15 min, there was definite
      gross and histologic evidence of severe ileitis upon necropsy at one week after
      instillation. The histopathology was more consistent with Th-1- than Th-2
      mediated inflammation.

PMID- 11991625
TI  - Sugar intolerance: origin and mechanisms of symptoms?
AB  - The origin and mechanisms of symptoms in sugar intolerance were studied in 8
      healthy volunteers. For two test periods, volunteers swallowed a probe with
      perfused catheters and an infusion catheter which migrated into the colon. A meal
      containing 40 g lactulose or 40 g sucrose was ingested; the sucrose meal was
      followed by colonic infusion of 40 g lactulose in order to bypass the small
      intestine. Recordings of small intestinal and colonic motility were performed.
      Abdominal pain, bloating, borborygmi, and flatulence were similar during both
      periods. Both meals increased small intestinal and colonic motility. Only 37% of
      the symptoms coincided in time with colonic motor events. Symptoms were not
      related to a specific motor event and were not correlated with breath hydrogen
      excretion. In conclusion, symptoms of sugar intolerance originate from the colon.
      They are not related to specific phasic motor events or to breath hydrogen
      excretion.

PMID- 11991626
TI  - 16,16-Dimethyl prostaglandin E2 inhibits indomethacin-induced small intestinal
      lesions through EP3 and EP4 receptors.
AB  - We evaluated the effect of various PGE analogs specific to EP receptor subtypes
      on indomethacin-induced small intestinal lesions in rats and investigated the
      relationship of EP receptor subtype with the PGE action using EP receptor
      knockout mice. Animals were administered indomethacin subcutaneously, and they
      were killed 24 hr later. 16,16-dimethyl prostaglandin E2 (dmPGE2) or various EP
      agonists were administered intravenously 10 min before indomethacin. Indomethacin
      caused hemorrhagic lesions in the rat small intestine, accompanied with an
      increase in intestinal motility and the number of enteric bacteria as well as
      iNOS and MPO activities. Prior administration of dmPGE2 dose-dependently
      prevented intestinal lesions, together with inhibition of those functional
      changes. These effects of dmPGE2 were mimicked by prostanoids (ONO-NT-012 and ONO
      AE1-329), only specific to EP3 or EP4 receptors, although the intestinal motility
      was inhibited only by ONO-AE1-329. Intestinal mucus secretion and fluid
      accumulation were decreased by indomethacin but enhanced by dmPGE2, ONO-NT-012,
      and ONO-AE1-329 at the doses that prevented intestinal lesions. Indomethacin also
      caused intestinal lesions in both wild-type and knockout mice lacking EP1 or EP3
      receptors, yet the protective action of dmPGE2 was observed in wild-type and EP1
      receptor knockout mice but not the mice lacking EP3 receptors. These results
      suggest that the intestinal cytoprotective action of PGE2 against indomethacin is
      mediated by EP3/EP4 receptors and that this effect is functionally associated
      with an increase of mucus secretion and enteropooling as well as inhibition of
      intestinal hypermotility, the former two processes mediated by both EP3 and EP4
      receptors, and the latter by EP4 receptors.

PMID- 11991627
TI  - Mechanisms involved in the attenuation of intestinal toxicity induced by (S)-(+)
      ketoprofen in re-fed rats.
AB  - In addition to suppression of prostaglandins synthesis a number of factors have
      been implicated in nonsteroidal antiinflammatory drugs (NSAIDs) enteropathy,
      including oxygen radical-dependent microvascular injuries, depletion of
      glutathione, and food. Inflammatory cytokines such as tumor necrosis factor-alpha
      regulate endothelial adhesion molecules expression and promote vascular
      neutrophil adherence. Racemic ketoprofen is a potent NSAID with a chiral
      structure existing in two enantiomeric forms. Its therapeutic effects reside
      almost exclusively in the (S)-(+) isomer nevertheless the potential contribution
      to side effects of the (R)-(-) isomer cannot be ignored. The aims of this study
      were to explore the role of prostaglandins depletion, tumor necrosis factor-alpha
      production, and glutathione homeostasis in the comparative pathogenesis of
      intestinal injury induced by racemic-ketoprofen and its enantiomers in re-fed
      rats. Racemic ketoprofen and (R)-(-)-ketoprofen dose-dependently caused similar
      and multiple lesions in the mid-jejunum significantly higher than those observed
      with (S)-(+)-ketoprofen. All the treatments significantly decreased
      prostaglandins content. A significant increase of tumor necrosis factor-alpha
      production and decreases in glutathione levels and glutathione reductase activity
      after treatment of the racemate and (R)-(-)-ketoprofen, were observed whereas the
      (S)-(+)-isomer did not change these parameters. In conclusion, (S)-(+)-ketoprofen
      possesses a better intestinal toxicity profile than the racemate and its (R)-(-)
      isomer. Despite inhibiting cyclooxygenase activity, the attenuation of (S)-(+)
      ketoprofen-induced intestinal toxicity could be correlated with a reduced
      oxidative damage characterized not only by a lack of changes in glutathione
      reductase activity and glutathione levels but also by an absence of up-regulation
      of tumor necrosis factor-alpha production in intestinal mucosa.

PMID- 11991628
TI  - Evolution of visceral sensitivity in patients with irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) has been associated with visceral
      hypersensitivity. Here we examined the evolution of rectal sensitivity and of
      gastrointestinal symptomatology in IBS patients over time, to verify if the
      clinical and biological parameters showed parallel behavior. Patients complaining
      of IBS, identified by Rome 1 criteria, were included in this study. The severity
      of the gastrointestinal (Gastrointestinal) symptoms was assessed by a
      gastrointestinal index. The pain threshold to rectal distension was measured by a
      barostat programmed for phasic ascending distensions. Both measures were obtained
      before and after treatment. Thirty-nine patients were followed while on a 10-week
      group psychotherapy (psy) program. Twelve patients were controlled after
      pharmacological treatment with amitriptyline (Ami) 10 mg hours for two weeks and
      then 25 mg hours for the following 4 weeks. Clinical improvement with symptom
      reduction was achieved in both patients groups. With psy, the Gastrointestinal
      index declined from an initial value of 78.4 +/- 4.8 to 65.5 +/- 4.5 at the end
      of treatment (P < 0.05). With Ami, the gastrointestinal index decreased from 91.6
      +/- 5.6 to 61.8 +/- 9.1 (p < 0.01). The pain threshold to rectal distension
      increased from 27.7 +/- 1.0 to 33.7 +/- 1.9 mmHg (P < 0.01) after drug treatment,
      but remained unchanged (30.6 +/- 1.0 vs 30.6 +/- 1.1 mm Hg) with psy. Evolution
      of the gastrointestinal index and rectal sensitivity were directly correlated (r
      = -0.71; P < 0.01) in Ami patients, but not in those treated with Psy (r = 
      0.001). In conclusion, visceral hypersensitivity appeared as a stable biological
      defect over a 10- to 12-week period during clinically-effective treatment with
      psychotherapy. Rectal pain threshold, however, seemed to be pharmacologically
      manipulatable in patients treated with Ami.

PMID- 11991629
TI  - Butyrate strongly inhibits in vitro stimulated release of cytokines in blood.
AB  - We studied the in vitro effects of butyrate on the stimulated release of
      proinflammatory cytokines and cytokines involved in the Th-1/Th-2 balance using
      the whole-blood model in nine healthy humans. Cytokines were measured without
      (control) and after stimulation by bacterial lipopolysaccharides (LPS) and
      phytohemagglutinin (PHA) alone or with addition of butyrate at six different
      concentrations (0.0625, 0.125, 0.25, 0.5, 1, and 2 mM). We found that butyrate at
      the six tested concentrations induced a significant decrease (P < 0.001) in the
      stimulated release of TNF-alpha, IFN-gamma, and IL-12, whereas IL-6 release was
      not altered. At concentrations > or = 0.25 mM, butyrate significantly reduced the
      stimulated release of IL-5, IL-10, and IL-13; the stimulated release of IFN
      gamma, IL-12, IL-5, and IL-13 was nearly abolished when compared to the
      unstimulated control sample. We concluded that butyrate has a wide spectrum of
      inhibitory activity on cytokine release stimulated by LPS + PHA in a whole-blood
      model. Confirmation of these results on colonic samples would show that butyrate
      is a factor by which the luminal contents may modulate the immune system in order
      to maintain the colonic mucosa in a noninflammatory state.

PMID- 11991630
TI  - Bacterial translocation and intestinal morphological findings in jaundiced rats.
AB  - The susceptibility to sepsis in obstructive jaundice may be related to bacterial
      translocation (BT) from the gastrointestinal tract. We evaluated BT to visceral
      organs and morphological changes of the intestinal mucosa in a rat model of
      obstructive jaundice. Animals were randomly divided into two groups: in group A
      the common bile duct was tied and divided, while group B had the bile duct
      mobilized but not tied. After seven days, peritoneal swabs and liver, spleen,
      pancreas, lung, mesenteric lymph nodes (MLN), cecum, and terminal ileum biopsies
      were obtained for cultures. Light and electron microscopy were performed on
      intestinal samples. The TUNEL assay was performed to detect apoptosis. Data were
      analyzed using Fisher exact test and Student t test. Bile duct obliteration
      resulted in an increased incidence of BT. Seven days after duct obliteration, BT
      to the peritoneal cavity was evident in 37.5% of the animals in group A and 25%
      in group B. The respective BT rates for the two groups were: 42.8% vs 37.5% to
      MLN, 71.4% vs 25% to liver, 42.8% vs 12.5% to spleen, 28.6% vs 0% to pancreas and
      14.3% vs 0% to lungs. Despite a trend, this was not statistically significant.
      Cecal counts did not differ statistically among the groups, while ileal counts
      were significantly higher in jaundiced rats (P < 0.05). Structural and
      ultrastructural abnormalities were evident only in the mucosa of the terminal
      ileum of jaundiced rats. Apoptosis was significantly increased in the terminal
      ileum of jaundiced rats (P < 0.002). This study suggests the possible association
      of biliary obstruction and BT. The nonspecific physical injury observed may
      contribute to breakdown of gastrointestinal barrier function thus promoting BT.

PMID- 11991631
TI  - A 24-kDa collagenase from Gymnorhynchus gigas elicits rat ileum hyperreactivity
      and is a target of humoral responses in mice previously given a single oral dose
      of parasite extract.
AB  - Fish declared fit to be eaten may contain plerocercoids (larvae) of the fish
      cestode Gymnorhynchus gigas. We showed previously that crude G. gigas larval
      extract given in a once-only oral dose to either mice or rats induces parasite
      specific immediate-type responses and that this extract evokes increased
      contractile activity in normal rat ileums. We show here that a 24-kDa collagenase
      (24-kCol), purified from the crude extract is (1) a target of both local
      (intestinal) and systemic IgE responses in mice sensitized by oral G. gigas and
      (2) elicits considerable changes in rat ileum contractility. Exposure of rat
      ileum segments once to 7 microg 24-kCol significantly increased tone and
      amplitude, but not frequency, of contractions compared with control recordings.
      In all, these studies have indicated 24-kCol, an abundantly produced protein of
      G. gigas larvae, to be a participant in potentially serious/adverse intestinal
      responses in both mice and rats. Such responses are very likely to occur in
      "sensitized" humans also.

PMID- 11991632
TI  - Circulating lysozyme and hepatic CYP1A activities during a chronic dietary
      exposure to tributyltin (TBT) and 3,3',4,4',5-pentachlorobiphenyl (PCB-126)
      mixtures in channel catfish, Ictalurus punctatus.
AB  - Exposure to planar congeners of halogenated aromatic hydrocarbons (HAHs) leads to
      a myriad of toxicities, including developmental, reproductive, and immunotoxic
      effects. Halogenated aromatic hydrocarbons possessing structural similarity to
      TCDD, such as 3,3',4,4',5-pentachlorobiphenyl (PCB-126), are more prevalent in
      the environment than TCDD, and they elicit similar toxic effects, primarily
      through the cytosolic aromatic hydrocarbon receptor (AhR). While polychlorinated
      biphenyls (PCBs) are ubiquitous pollutants, they rarely exist alone in the
      environment. The aquatic biocide tributyltin (TBT) is also a widespread
      environmental contaminant, and numerous studies indicate that it has
      reproductive, developmental, and immunotoxic effects in a variety of organisms.
      Unlike planar HAHs, TBT is not associated with any known cellular receptor. The
      induction of cytochrome P-4501A (CYP1A) activity in most vertebrates is a
      classical physiological response to planar HAH exposure. TBT has been shown to
      inhibit the induction of cytochrome P-4.50s at high doses. Recent studies
      demonstrate that low levels of TBT potentiate PCB-126-associated CYP1A induction
      in channel catfish, Ictalurus punctatus, and in rodents following intraperitoneal
      injections. In this study, the effects of dietary exposures to TBT, PCB-126, and
      mixtures of the two on channel catfish hepatic CYP1A activity, as well as plasma
      lysozyme activity, were examined. Circulating lysozyme, a marker of
      proinflammatory responses, was monitored to determine the relative specificity of
      treatments for CYP1A induction. Plasma lysozyme levels were examined along with
      hepatic CYP1A protein induction and EROD activity following exposure to nominal
      doses of 1 and 100 ppb dietary TBT, PCB-126, or mixtures of the two. As expected,
      the highest level of PCB-126 induced CYP1A, and TBT did not. In mixtures, the low
      level of TBTpotentiated the ability of the high PCB-126 dose to induce CYP1A.
      Plasma lysozyme levels were suppressed by both concentrations of TBT and by the
      low concentrations of PCB- 126 during the initial phase of the response to Vibrio
      anguillarum. The normal and expected pattern of initial increases in circulating
      lysozyme levels following immunization, with subsequent return to baseline level,
      was disrupted by TBT. High levels of PCB-126 potentiated the lysozyme response.
      As seen with CYP1A activities, exposures to mixtures of TBT and PCB-126 resulted
      in a potentiation of plasma lysozyme levels. The data show that dietary TBT
      modulates PCB- 126-induced CYP1A activities and that these mixtures may have
      potent proinflammatory properties as well.

PMID- 11991633
TI  - In vivo and in vitro modulation of carp (Cyprinus carpio L.) phagocyte oxidative
      burst activity by gallium.
AB  - Since gallium is a metal ion used in semiconductor industry, the toxicological
      effects were previously evaluated in mammals but the ecotoxicological impacts
      remain unknown. In term of ecotoxicological risk assessment, the median lethal
      concentration (LC50 for 96 h of gallium to carp (Cyprinus carpio L.) and the
      oxidative response of carp phagocytes after the fish were exposed to sublethal
      levels of gallium were determined. The LC50 of gallium on C. carpio at 96 h was
      estimated as 96.25 +/- 14.3 mg/L. To determine the effect in vivo of gallium on
      the phagocyte response, fish were exposed for 96 h to 5 or 50 mg Ga(3+)/L. Carp
      maintained for 48 or 96 h in water containing 50 mg/L gallium had a significant
      fall in phagocyte oxidative burst activity in comparison with controls, as well
      as decreased leukocyte number in blood and increased cytotoxicity. To determine
      the effect in vitro of gallium on the phagocyte response, isolated phagocytes
      were exposed for 5 or 15 min to 50 nM, 500 nM, or 5, 50, 100, or 200 microM of
      Ga(3+). The oxidative burst was increased after in vitro incubation of phagocytes
      with 50 or 500 nM gallium for 15 min or with 500 nM gallium for 5 min. Moreover,
      for 50, 100, or 200 microM gallium, the oxidative burst activity of carp
      phagocytes was significantly decreased. Results indicate that the lethal toxicity
      of gallium for carp of gallium is not as high as for other metal ions. However,
      gallium was immunosuppressive for carp at the highest concentrations used (from
      50 microM) in vivo and in vitro. At low concentrations, it could be an
      immunostimulant as observed in vitro.

PMID- 11991634
TI  - Mercuric chloride acting through Mg stimulates protein synthesis in Xenopus
      oocytes.
AB  - In Xenopus laevis oocytes, addition of HgCl2 (Hg) to the medium rapidly
      stimulated incorporation of [35S]methionine (MET) into protein, increasing
      incorporation up to five-fold over control values. The action of inorganic
      mercury persisted after removal of Hg. Microinjection of HgCl2 into oocytes
      maintained in buffer also increased MET incorporation. However, no such
      stimulation was found when Hg was microinjected into oocytes maintained under
      oil, suggesting that Hg action was dependent on a cell-medium interaction.
      Removing medium Mg2+ decreased insulin- and Hg-stimulated methionine
      incorporation. Increasing medium Mg2+ from 1 mM to 10 mM increased Hg-stimulated
      methionine incorporation twofold. Hypotonic swelling of oocytes stimulated hexose
      transport but inhibited protein synthesis. Together these data indicate that
      inorganic mercury activates translation in the oocyte through an Mg-dependent
      mechanism, possibly increased Mg2+ influx.

PMID- 11991635
TI  - Vitamin E supplementation in streptozotocin-treated rats alters cerebellar and
      plasma nitric oxide metabolism.
AB  - Nitric oxide (NO) free radicals appear to contribute to the pathogenesis of a
      number of disorders including diabetes mellitus. The aim of this study was to
      determine the effects of streptozotocin (STZ)-induced diabetes on nitric oxide
      (NO) metabolites in plasma and cerebellar nitric oxide synthase (NOS) activity.
      Further, it was of interest to determine whether an antioxidant, vitamin E, could
      reverse the STZ-induced effects. STZ significantly decreased cerebellar NOS but
      increased the level of plasma total nitrite + nitrate and the level of plasma
      nitrate. Supplementation with vitamin E effectively reduced the STZ-induced
      effects. Data demonstrate that vitamin E may serve as a protective antioxidant in
      STZ-induced diabetes.

PMID- 11991636
TI  - Osmolytes stimulate the reconstitution of functional 50S ribosomes from in vitro
      transcripts of Escherichia coli 23S rRNA.
AB  - Functional Escherichia coli 50S ribosomal subunits can be reconstituted from
      their natural rRNA and protein components. However, when the assembly is
      performed with in vitro-transcribed 23S rRNA, the reconstitution efficiency is
      diminished by four orders of magnitude. We tested a variety of chemical
      chaperones (compounds that are typically used for protein folding), putative RNA
      chaperones (proteins) and ribosome-targeted antibiotics (small-molecule ligands)
      that might be reasoned to aid in folding and assembly. Addition of the osmolyte
      trimethylamine-oxide (TMAO) and the ketolide antibiotic telithromycin (HMR3647)
      to the reconstitution stimulates its efficiency up to 100-fold yielding a
      substantially improved system for the in vitro analysis of mutant ribosomes.

PMID- 11991637
TI  - A novel mechanism for protein-assisted group I intron splicing.
AB  - Previously it was shown that the Aspergillus nidulans (A.n.) mitochondrial COB
      intron maturase, I-AniI, facilitates splicing of the COB intron in vitro. In this
      study, we apply kinetic analysis of binding and splicing along with RNA deletion
      analysis to gain insight into the mechanism of I-AniI facilitated splicing. Our
      results are consistent with I-AniI and A.n. COB pre-RNA forming a specific but
      labile encounter complex that is resolved into the native, splicing-competent
      complex. Significantly, kinetic analysis of splicing shows that the resolution
      step is rate limiting for splicing. RNA deletion studies show that I-AniI
      requires most of the A.n. COB intron for binding suggesting that the integrity of
      the I-AniI-binding site depends on overall RNA tertiary structure. These results,
      taken together with the observation that A.n. COB intron lacks significant stable
      tertiary structure in the absence of protein, support a model in which I-AniI
      preassociates with an unfolded COB intron via a "labile" interaction that
      facilitates correct folding of the intron catalytic core, perhaps by resolving
      misfolded RNAs or narrowing the number of conformations sampled by the intron
      during its search for native structure. The active intron conformation is then
      "locked in" by specific binding of I-Anil to its intron interaction site.

PMID- 11991638
TI  - Purification and characterization of native spliceosomes suitable for three
      dimensional structural analysis.
AB  - We describe characterization of spliceosomes affinity purified under native
      conditions. These spliceosomes consist largely of C complex containing splicing
      intermediates. After C complex assembly on an MS2 affinity-tagged pre-mRNA
      substrate containing a 3' splice site mutation, followed by RNase H digestion of
      earlier complexes, spliceosomes were purified by size exclusion and affinity
      selection. This protocol yielded 40S C complexes in sufficient quantities to
      visualize in negative stain by electron microscopy. Complexes purified in this
      way contain U2, U5, and U6 snRNAs, but very little U1 or U4 snRNA. Analysis by
      tandem mass spectrometry confirmed the presence of core snRNP proteins (SM and
      LSM), U2 and U5 snRNP-specific proteins, and the second step factors Prp16,
      Prp17, Slu7, and Prp22. In contrast, proteins specific to earlier splicing
      complexes, such as U2AF and U1 snRNP components, were not detected in C complex,
      but were present in similarly purified H complex. Images of these spliceosomes
      revealed single particles with dimensions of approximately 270 x 240 A that
      assort into well-defined classes. These images represent an important first step
      toward attaining a comprehensive three-dimensional understanding of pre-mRNA
      splicing.

PMID- 11991639
TI  - Solution structure of an RNA fragment with the P7/P9.0 region and the 3'-terminal
      guanosine of the tetrahymena group I intron.
AB  - In the second step of the two consecutive transesterifications of the self
      splicing reaction of the group I intron, the conserved guanosine at the 3'
      terminus of the intron (omegaG) binds to the guanosine-binding site (GBS) in the
      intron. In the present study, we designed a 22-nt model RNA (GBS/omegaG)
      including the GBS and omegaG from the Tetrahymena group I intron, and determined
      the solution structure by NMR methods. In this structure, omegaG is recognized by
      the formation of a base triple with the G264 x C311 base pair, and this
      recognition is stabilized by the stacking interaction between omegaG and C262.
      The bulged structure at A263 causes a large helical twist angle (40 +/- 80)
      between the G264 x C311 and C262 x G312 base pairs. We named this type of binding
      pocket with a bulge and a large twist, formed on the major groove, a "Bulge-and
      Twist" (BT) pocket. With another twist angle between the C262 x G312 and G413 x
      C313 base pairs (45 +/- 100), the axis of GBS/omegaG is kinked at the GBS region.
      This kinked axis superimposes well on that of the corresponding region in the
      structure model built on a 5.0 A resolution electron density map (Golden et al.,
      Science, 1998, 282:345-358). This compact structure of the GBS is also consistent
      with previous biochemical studies on group I introns. The BT pockets are also
      found in the arginine-binding site of the HIV-TAR RNA, and within the 16S rRNA
      and the 23S rRNA.

PMID- 11991640
TI  - Inhibition of translation by RNA-small molecule interactions.
AB  - Small molecule ligand-RNA interactions have the potential to influence gene
      expression at a variety of steps and in a number of ways. Here, we demonstrate
      that such interactions are sufficiently stable to inhibit translation of
      eukaryotic mRNAs in vitro and in vivo. Inhibition is only observed when the 5'
      UTR of the mRNA is targeted, and the response is proportional to the number of
      binding sites within this region. We find that small molecule ligand-RNA
      interactions can be sufficiently stable to prevent 80S ribosome assembly on an
      mRNA template. The ability to specifically ablate expression of a defined mRNA
      with a small molecule ligand demonstrates proof of principle for pharmacological
      targeting aimed at controlling translation of specific mRNAs.

PMID- 11991641
TI  - Delta ribozyme benefits from a good stability in vitro that becomes outstanding
      in vivo.
AB  - The stability of a trans-acting delta ribozyme was studied under various
      conditions. Although in vitro (i.e., in the presence of protein extracts) this
      delta ribozyme appears to be only slightly more stable than a hammerhead
      ribozyme, in vivo (i.e., after cell transfection) it exhibits an outstanding
      stability that manifests itself in the calculated half-life of over 100 h
      regardless of the means of transfection. The P2 stem, which includes both the 5'
      and 3' ends, is shown to play a critical role in this stability. Direct
      mutagenesis of the most nuclease susceptible nucleotides failed to generate a
      more stable ribozyme that retained the same catalytic potential. Clearly, delta
      ribozyme appears to be well adapted to the human cell environment, and is
      therefore ideal for the development of a gene-inactivation system.

PMID- 11991642
TI  - The mRNA of the translationally controlled tumor protein P23/TCTP is a highly
      structured RNA, which activates the dsRNA-dependent protein kinase PKR.
AB  - The dsRNA-activated protein kinase PKR is involved in signal transduction
      pathways that mediate cellular processes as diverse as cell growth and
      differentiation, the stress response, and apoptosis. PKR was originally described
      as an interferon-inducible elF2alpha kinase involved in the antiviral defense
      mechanism of the cell. The interaction of the kinase with specific viral RNAs has
      been studied in much detail, but information about cellular mRNAs, which are able
      to bind and activate PKR, is scarce. In search for such cellular mRNAs, we
      developed a cloning strategy to identify individual mRNA species from the dsRNA
      rich fraction of Daudi cell poly(A)+ RNA. Two out of five cDNA clones we obtained
      contained sequences derived from the mRNA of the translationally controlled tumor
      protein P23/TCTP, indicating that this mRNA is present in the dsRNA-rich
      fraction. Secondary structure predictions and gel electrophoretic mobility
      investigations on P23/TCTP transcripts confirmed the potential of this mRNA to
      form extensive secondary structure. A full-length P23 transcript, but not a
      truncated version thereof, was able to bind to PKR in vitro and in vivo.
      Transient transfection experiments in human 293 cells showed that coexpression of
      full-length P23 mRNA leads to partial inhibition of the expression of a beta
      galactosidase reporter gene in trans. Additional coexpression of a dominant
      negative mutant of PKR or of adenovirus VA1 RNA suppressed this inhibition,
      indicating that it is mediated by PKR. Studies on P23/TCTP expression in cells
      from PKR-knockout mice suggest that P23/TCTP mRNA translation is regulated by
      PKR. Hence, our results demonstrate that the mRNA of P23/TCTP may both activate
      PKR and be subject to translational regulation by this kinase.

PMID- 11991643
TI  - Transcript abundance supercedes editing efficiency as a factor in developmental
      variation of chloroplast gene expression.
AB  - In maize plastids, transcripts are known to be modified at 27 C-to-U RNA editing
      sites, affecting the expression-of 15 different genes. The relative contribution
      of editing efficiency versus transcript abundance in regulation of chloroplast
      gene expression has previously been analyzed for only a few genes. We undertook a
      comprehensive analysis of the editing efficiency of each of the 27 maize editing
      sites in 10 different maize tissues, which contain a range of plastid types
      including chloroplasts, etioplasts, and amyloplasts. Using a reproducible
      poisoned primer extension assay, we detected variation between RNA editing extent
      of different sites in the same transcript in the same tissue, and between the
      same site in different tissues. The most striking editing deficiency is in an
      editing site in ndhB that is edited at only 8% and 1% in roots and callus
      plastids respectively, whereas green leaf chloroplasts edit this site at 100%.
      Editing efficiencies of some sites are not affected by the developmental stages
      we examined and are always edited close to 80-100%. The relative amounts of
      transcripts of each of the 10 genes that exhibited variable editing extents were
      determined by real-time PCR. Seven genes exhibited over 100 times lower
      transcript abundance in either roots or tissue-cultured cells relative to green
      leaf tissue. The quantitative analysis indicates that a particular editing site
      can be efficiently edited over a large range of transcript abundance, resulting
      in no general correlation of transcript abundance and editing extent. The
      independent variation of editing efficiency of different sites within the same
      transcript fits with a model that postulates individual trans-acting factors
      specific to each editing site. Because tissues where editing efficiency at
      certain sites is low invariably also exhibited greatly decreased abundance of the
      transcripts carrying those sites, decrease in the amounts of particular RNAs
      rather than a lack of editing is predicted to have the most significant impact on
      gene expression under steady-state conditions. Our data is consistent with the
      hypothesis that the role of editing in angiosperm plastids is to correct
      otherwise detrimental mutations rather than to generate significant protein
      diversity.

PMID- 11991644
TI  - Activation and evasion of the antiviral 2'-5' oligoadenylate
      synthetase/ribonuclease L pathway by hepatitis C virus mRNA.
AB  - Chronic hepatitis C virus (HCV) infections are a significant cause of morbidity
      and mortality worldwide. Interferon-alpha2b treatment, alone or in combination
      with ribavirin, eliminates HCV from some patients, but patients infected with HCV
      genotype 1 viruses are cured less frequently than patients infected with HCV
      genotype 2 or 3 viruses. We report that HCV mRNA was detected and destroyed by
      the interferon-regulated antiviral 2'-5' oligoadenylate synthetase/ ribonuclease
      L pathway present in cytoplasmic extracts of HeLa cells. Ribonuclease L cleaved
      HCV mRNA into fragments 200 to 500 bases in length. Ribonuclease L cleaved HCV
      mRNA predominately at UA and UU dinucleotides within loops of predicted stem-loop
      structures. HCV mRNAs from relatively interferon-resistant genotypes (HCV
      genotypes 1a and 1b) have fewer UA and UU dinucleotides than HCV mRNAs from more
      interferon-sensitive genotypes (HCV genotypes 2a, 2b, 3a, and 3b). HCV 2a mRNA,
      with 73 more UA and UU dinucleotides than HCV 1a mRNA, was cleaved by RNase L
      more readily than HCV 1a mRNA. In patients, HCV 1b mRNAs accumulated silent
      mutations preferentially at UA and UU dinucleotides during interferon therapy.
      These results suggest that the sensitivity of HCV infections to interferon
      therapy may correlate with the efficiency by which RNase L cleaves HCV mRNA.

PMID- 11991645
TI  - Regulation of alternative splicing by SRrp86 through coactivation and repression
      of specific SR proteins.
AB  - SRrp86 is an 86-kDa member of the SR protein superfamily that is unique in that
      it can alter splice site selection by regulating the activity of other SR
      proteins. To study the function of SRrp86, inducible cell lines were created in
      which the concentration of SRrp86 could be varied and its effects on alternative
      splicing determined. Here, we show that SRrp86 can activate SRp20 and repress
      SC35 in a dose-dependent manner both in vitro and in vivo. These effects are
      apparently mediated through direct protein-protein interaction, as pull-down
      assays showed that SRrp86 interacts with both SRp20 and SC35. Consistent with the
      hypothesis that relatively modest changes in the concentration or activity of one
      or more splicing factors can combinatorially regulate overall splicing, protein
      expression patterns of SRrp86, SRp20, and SC35 reveal that each tissue maintains
      a unique ratio of these factors. Regulation of SR protein activity, coupled with
      regulated protein expression, suggest that SRrp86 may play a crucial role in
      determining tissue specific patterns of alternative splicing.

PMID- 11991646
TI  - Lead(II) as a probe for investigating RNA structure in vivo.
AB  - In this communication, we describe a simple and reliable method for RNA structure
      determination in vivo, using the divalent ion, lead(II), as a structural probe.
      Lead(II) is known to cleave RNA within single-stranded regions, loops, and
      bulges, whereas cleavages in double-stranded regions are weaker or absent.
      Because the ion easily entered bacterial cells, Escherichia coli cultures were
      treated by addition of 50-100 mM lead(II) acetate for 3-7 min, resulting in
      partial cleavage of RNA in vivo. Cleavage positions were mapped by reverse
      transcription analysis of total extracted RNA. Three RNAs were analyzed: tmRNA,
      CopT (the target of the antisense RNA CopA), and the leader region of the ompF
      mRNA. All three RNAs had previously been analyzed in vitro, and secondary
      structure models were available. The results presented here show that lead(II)
      cleavages in vivo yield detailed structural information for these RNAs, which was
      in good agreement with the models proposed based on in vitro work. These data
      illustrate the potential of lead(II) as a sequence-independent RNA structure
      probe for use in living cells.

PMID- 11991647
TI  - MALDI-TOF mass spectrometry methods for evaluation of in vitro aminoacyl tRNA
      production.
AB  - Unnatural amino acid mutagenesis requires the in vitro production of aminoacyl
      tRNAs. Bacteriophage T4 RNA ligase is used to ligate a-amino-protected dCA amino
      acids to 74mer tRNA. Previously, there has been no facile method for evaluating
      the efficiency of this reaction prior to using the tRNA in translation. We report
      a novel use of matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry in monitoring the formation of aminoacyl 76mer tRNA. This method is
      more efficient and precise than the traditional technique of gel electrophoresis.
      These MALDI conditions should also prove useful for analyzing aminoacyl tRNAs
      produced through aminoacyl tRNA synthetases and other methods.

PMID- 11991648
TI  - A hammerhead ribozyme substrate and reporter for in vitro kinetoplastid RNA
      editing.
AB  - Current in vitro assays for RNA editing in kinetoplastids directly examine the
      products generated by incubation of pre-mRNA substrate with guide RNA (gRNA) and
      mitochondrial (mt) extract. RNA editing substrates that are modeled on hammerhead
      ribozymes were designed with catalytic cores that contained or lacked additional
      uridylates (Us). They proved to be sensitive reporters of editing activity when
      used for in vitro assays. A deletion editing substrate that is based on A6 pre
      mRNA had no ribozyme activity, but its incubation with gRNA and mt extract
      resulted in its deletion editing and production of a catalytically active
      ribozyme. Hammerhead ribozymes are thus sensitive tools to assay in vitro RNA
      editing.

PMID- 11991649
TI  - p53-like protein binding affinity to the hormone responsive element of the
      haptoglobin gene in fetal rat livers.
AB  - In order to identify nucleoproteins involved in transcriptional regulation of the
      haptoglobin (Hp) gene, fetal rat livers of dams exposed to inflammation on day 19
      of pregnancy were used. Previously observed acute phase-dependent elevation of Hp
      gene transcriptional activity in prenatal liver was accompanied by increased
      binding affinities of several fetal soluble nucleoproteins and the hormone
      response element (RE) of the Hp gene (-170/-56). One of these proteins, a hepatic
      nucleoprotein of 53 kDa, was identified by Western blotting analysis as a protein
      within the same molecular mass and epitopes as transcription factor p53. Also, in
      vitro phosphorylation experiments revealed that the examined fetal nucleoprotein
      could be liable to the same phosphorylative post-translational modification as
      p53. The obtained results suggest that the fetal 53 kDa-nucleoprotein could be a
      homologue of transcription factor p53, participating in the transcriptional
      modulation of the Hp gene throughout prenatal hepatic development.

PMID- 11991650
TI  - Effects of 3-D clino-rotation on gene expression in human fibroblast cells.
AB  - Continuous variation in the direction of the gravity vector leads to various
      cellular responses including modulation of gene expression. Complementary DNA
      (cDNA) array analyses are available to observe the variation of gene expression
      under different conditions. In this study, expression levels of 588
      representative genes were compared using the Atlas human cDNA expression array in
      human fibroblast cells with and without 3-dimensional (3-D) clinostat. Five
      upregulated and 8 downregulated genes were detected. Among these genes,
      upregulation of XRCC1, and downregulation of ERB-B2 and p21(Cip1/Waf1) were
      confirmed by RT-PCR. These results suggested that the gene expression levels of
      XRCC1, ERB-B2 and p21(Cip1/Waf1) were modulated by vector-averaged microgravity
      induced by 3-D clinostat in human fibroblast cells. Our findings may be a basis
      for the biological study of 3-D culture systems.

PMID- 11991651
TI  - Bisphenol a diglycidyl ether (BADGE) suppresses tumor necrosis factor-alpha
      production as a PPARgamma agonist in the murine macrophage-like cell line, RAW
      264.7.
AB  - Bisphenol A diglycidyl ether (BADGE) is a newly described peroxisome proliferator
      activated receptor gamma (PPARgamma) antagonist in adipogenic cells. In contrast,
      in the macrophage-like cell line RAW 264.7, BADGE, like the PPARgamma agonist
      pioglitazone hydrochloride, not only increased promoter activity of the PPARgamma
      luciferase reporter gene, but also suppressed lipopolysaccharide (LPS)-induced
      tumor necrosis factor-alpha (TNF-alpha) production. These results suggest that
      BADGE is a PPARgamma agonist in RAW 264.7 cells. Furthermore, overexpression of
      the coactivator p300 restored BADGE- or pioglitazone hydrochloride-suppressed
      promoter activity of the nuclear factor-kappa B (NF-kappaB)-luciferase reporter
      gene, suggesting that PPARgamma may interfere with NF-kappaB transcriptional
      activity via coactivator competition.

PMID- 11991652
TI  - Morphological characterization of cell death during the ovary differentiation in
      worker honey bee.
AB  - Cell death that occurs during ovary differentiation in the honeybee worker's
      larval development accounts for ovariole reabsorption. From a morphological
      standpoint, three modes of death were detected. Germinative cells in the
      ovarioles die by an apoptotic-like process, whereas the somatic cells die by an
      autophagic process, type II cell death; and during pupation, stromatic and
      ovarian capsular cells die through cytoplasmic disintegration, releasing their
      components into the hemolymph. These modes of cell death are in part determined
      by the pattern of tissue organization within which the cell occurs.

PMID- 11991653
TI  - Gap junction intercellular communication during lymphocyte transendothelial
      migration.
AB  - Migration of lymphocytes across the endothelium of central or peripheral tissues,
      a process occurring following activation or differentiation, involves cell to
      cell interactions featuring adhesion and heterotypic signalling 'cross-talk'.
      Since lymphocytes and endothelial cells express connexins, the subunit proteins
      of gap junction intercellular channels, we investigated whether these channels
      feature in heterotypic signalling during transendothelial migration of
      lymphocytes. We show, using FACS analysis, that calcein, a gap junction permeant
      fluorescent dye, was transferred from endothelial cell layers to lymphocytes. The
      gap junction involvement in intercellular dye transfer was reinforced by studies
      showing that the process was inhibited by connexin mimetic peptides, a new class
      of reagents shown to block gap junction communication. Further evidence for the
      involvement of lymphocyte gap junctions in intercellular communication during
      transendothelial migration was obtained by two-photon laser scanning microscopy.
      Although gap junctional communication was inhibited by connexin mimetic peptides,
      they had little influence on the transmigration process.

PMID- 11991654
TI  - Opposite effect of linearly polarized light on biosynthesis of interleukin-6 in a
      human B lymphoid cell line and peripheral human monocytes.
AB  - The effects of linearly polarized light (LPL) and diffuse light (DL) on the in
      vitro interleukin-6 (IL-6) production in a human B lymphoma cell line (BMNH) and
      peripheral monocytes of healthy volunteers were compared. Our data show that
      there was a significant increase of IL-6 and IgM production in BMNH after
      exposure to LPL. The increase in IgM secretion was a consequence of its autocrine
      regulation by IL-6, since in the presence of anti-IL-6 and anti-IL-6 receptor
      antibodies the LPL-induced IgM secretion was abolished. In contrast to the
      stimulatory effect on B cells, exposure of human mononuclear phagocytes to LPL
      markedly reduced the production of IL-6 induced by subsequent stimulation of
      cells with bacterial endotoxin (LPS). The inhibition as most pronounced when
      suboptimal doses of LPS were applied. Under identical experimental conditions, DL
      had no effect on the IL-6 and IgM production of either B cells or monocytes.

PMID- 11991655
TI  - 4-1BB-like molecule is expressed in islet-infiltrating mononuclear cells and in
      the gray matter of the brain.
AB  - 4-1BB is an inducible costimulatory molecule that can exert regulatory effects on
      T cells. Polyclonal antibodies against oligopeptides representing an
      evolutionarily-conserved region of murine 4-1BB, were prepared and used to stain
      tissues in normal and inflammatory conditions. The 4-1BB mRNA was detected in the
      PMA-treated spleen and heart, and constitutively in the brain, kidneys and lungs.
      The 4-1BB-like protein (BBLP) was expressed on mononuclear cells infiltrating
      islet cells in the pancreata of NOD mice. Expression was prominent in the early
      phase of insulitis and the level of expression diminished or disappeared in the
      later phase. BBLP was identified in the gray matter of brain where neuronal cell
      bodies, dendrites, and fiber terminals reside but was almost entirely absent in
      the white matter where axonal fibers dwell. A peculiar rosette pattern was
      observed in a granular layer of cerebellum and scattered in the stria terminalis.
      The staining pattern strongly resembled the receptor/nerve terminals in the brain
      and in the peripheral nervous system. Taken together, BBLP may be associated with
      the early phase of inflammation and with brain function.

PMID- 11991656
TI  - The coupling of vinculin to the cytoskeleton is not essential for mechano
      chemical signaling in F9 cells.
AB  - It is well established that mechanical forces can regulate cell growth and guide
      tissue remodeling, yet little is known about how mechanical signals act at the
      cell surface membrane to produce biochemical changes in the cell. To explore this
      question, I used a mouse embryonic F9 vinculin-deficient cell line (gamma229),
      which, unlike wild-type cells, shows no fibronectin-dependent cell spreading. The
      wild-type cell line exhibited a twofold increase in area over four hours. I
      observed (i) an earlier rise in intracellular free calcium from approximately 0.2
      to approximately 3 microm in wild-type compared with gamma229 cells, thus similar
      calcium levels after 4 h; (ii) an initial higher ratio of p-MAP/MAP-Kinase for
      gamma229, but similar FA-Kinase activation; and (iii) a marginal change in
      intracellular pH [pH](i) in both F9 cell lines. When I applied controlled local
      stresses directly to integrin receptors using RGD-coated magnetic beads, they
      displaced to a lesser extent in wild-type than in gamma229 cells. Both F9 cell
      lines showed a small stress-dependent rise in [Ca2+]i levels and similar PKA-c
      activity. In summary, the mechanical linkage of integrin-vinculin-cytoskeleton
      seemed not to be essential for chemical signal transduction.

PMID- 11991657
TI  - Myosin II redistribution during rear retraction and the role of filament assembly
      and disassembly.
AB  - The literature to date suggests a role for myosin II in rear retraction,
      including evidence that myosin undergoes a characteristic 'C'-to-spot
      redistribution at the cell posterior which is associated with retraction. Here we
      investigate the mechanism of both retraction and the'C'-to-spot using
      Dictyostelium cells containing mutant forms of myosin that affect its
      polymerization. 3 x Asp-myosin forms few if any filaments. When 3 x Asp cells are
      added to a wild-type mound, the mutant cells move directionally, but rear
      retraction is markedly delayed,demonstrating that myosin II filaments are
      essential for efficient retraction. In addition, using a GFP-tagged 3 x Asp
      myosin, we observed a posterior spot pattern associated with retraction,but no
      cortical 'C' pattern preceding it. This suggests that filamentous myosin is
      required to produce the 'C', and that its failure to form results in defective
      rear retraction. In contrast, an alternate mutant myosin that forms filaments
      constitutively, 3 x Ala-myosin, forms 'Cs' and then spot patterns at the
      posterior, but in the interim the spots do not disintegrate. This suggests that
      spot dissolution occurs by filament depolymerization. In summary our data
      demonstrate a role for myosin II and the 'C'-to-spot in efficient rear
      retraction, and define filament assembly as critical for formation of the 'C' and
      filament disassembly as critical for dissolution of the spot.

PMID- 11991658
TI  - Human articular chondrocytes express three facilitative glucose transporter
      isoforms: GLUT1, GLUT3 and GLUT9.
AB  - Glucose is an important metabolite and a structural precursor for articular
      cartilage and its transport has significant consequences for cartilage
      development and functional integrity. In this study the expression of
      facilitative glucose transporters (GLUTs) in human chondrocytes was investigated.
      Results showed that at least three GLUT isoforms (GLUT1, GLUT3 and GLUT9) are
      expressed by normal chondrocytes. Given the central role of glucose in
      chondrocyte physiology and metabolism, its regular provision via GLUTs will
      influence the metabolic activity and survival of chondrocytes in cartilage
      matrices.

PMID- 11991659
TI  - Life, cells, heterodoxy and survival: problems of the exclusion principle.

PMID- 11991660
TI  - Mechanical aspects of cell shape regulation and signaling.
AB  - Physical forces play a critical role in cell integrity and development, but
      little is known how cells convert mechanical signals into biochemical responses.
      This mini-review examines potential molecular mediators like integrins, focal
      adhesion proteins, and the cytoskeleton in the context of a complex cell
      structure. These molecules-when activated by cell binding to the extracellular
      matrix-associate with the skeletal scaffold via the focal adhesion complex.
      Vinculin is presented as a mechanical coupling protein that contributes to the
      integrity of the cytoskeleton and cell shape control, and examples are given of
      how mechanical signals converge into biochemical responses through force
      dependent changes in cell geometry and molecular mechanics.

PMID- 11991661
TI  - Over-expression of K-FGF or bFGF results in altered expression of matrix
      metalloproteinases: correlations with malignant progression and cellular
      invasion.
AB  - Matrix metalloproteinase (MMP) expression was investigated in NIH-3T3 fibroblasts
      that secrete K-FGF and in NIH-3T3 cells which express chimeric bFGF with a signal
      sequence targeting bFGF to the secretory pathway. Correlations between altered
      MMPs' and other proteases' expression and malignant potential were determined.
      Correlations between the expression of MMPs and the invasion ability of K-FGF and
      bFGF over-expressing cells were also determined. The resulting correlation
      between alterations in proteases and malignant progression supports a model which
      suggests that growth factor modulation of protease expression is part of the
      altered growth regulatory program associated with cellular transformation and
      malignant progression.

PMID- 11991662
TI  - Receptor-bound uPA is reversibly protected from inhibition by low molecular
      weight inhibitors.
AB  - Urokinase-type plasminogen activator (uPA) plays a ubiquitous role in cell
      migration and invasiveness. Amiloride, a competitive inhibitor of uPA, can
      inhibit endothelial cell (EC) outgrowth during angiogenesis. To address the
      question of whether amiloride blocked angiogenesis by inhibiting uPA, we
      undertook a study of uPA expression in sprouting EC in vitro and the effects of
      amiloride on both enzymatic and morphogenetic activity. As expected, amiloride
      inhibited soluble uPA (suPA) with an IC(50) of 45-85 microm, however, receptor
      bound uPA (rbuPA) from the sprouting EC was insensitive to amiloride. Removal of
      uPA from its receptors confers sensitivity to inhibition by amiloride suggesting
      that a reversible conformational change may mediate the insensitivity of rbuPA to
      amiloride and its analogs. In summary, we found no evidence to support the
      hypothesis that amiloride blocks capillary outgrowth by inhibition of uPA, but
      were able to successfully demonstrate a functional difference between two
      physiological forms of this important matrix-degrading enzyme.

PMID- 11991663
TI  - In vitro behaviour of human osteoblasts on dentin and bone.
AB  - This investigation studied how the behaviour of isolated osteoblasts on standard
      tissue culture polystyrene compared with cells cultured on cut surfaces of
      dentin, a natural calcified material. Cellular attachment, viability and growth
      were monitored in parallel cultures of human osteosarcoma cell lines (MG63, HOS
      TE85, SaOS-2) and primary human osteoblast-like cells (HOBs). Culture plastic was
      either left untreated or roughened with abrasive paper of various grit sizes
      (4000-1200 grit) in order to obtain a level of roughness comparable to that of
      the dentin slices. Cell counting and intracellular BCECF staining showed that
      after an initial incubation of 2 h, the primary cells attached and spread out
      more quickly on the different substrates than the three cell lines. The primary
      cells also showed a stronger mitochondrial staining and viability on dentin.
      During subsequent culture morphological differences appeared with the cells on
      dentin displaying more cellular extensions. All three cell lines proliferated
      more slowly on dentin than on plastic. In contrast, the primary HOBs were not
      significantly affected in their growth by the different substrates. Total and
      specific alkaline phosphatase (AP) activity of the cell lines was not
      significantly affected by the different substrates after short-term adhesion, but
      it was increased for the primary cells on the dentin. However, after 2-3 days of
      culture, AP was decreased on the dentin slices for both the cell lines and
      primary HOBs. Plasma treatment of the roughened plastic did not alter cellular
      viability or AP activity, suggesting that grinding of the surface did not affect
      the property of the culture plastic to support cell attachment and growth. In
      conclusion, the results show that not only do osteoblastic cells behave
      differently on a natural calcified substrate surface than on standard culture
      plastic, but also that differences were evident between the various cell types,
      in particular the primary HOB versus the continuous cell lines.

PMID- 11991664
TI  - Changes in fused cells induced by hvj (sendai virus): redistribution of
      cytoplasmic organelles and cytoskeletal reorganization.
AB  - To understand the relationship between the location of organelles and cellular
      function, we examined the dynamic state of cytoplasmic organelles and
      cytoskeleton in polynuclear Ehrlich ascites tumor (EAT) cells fused with
      hemagglutinating virus of Japan (HVJ; Sendai virus) by confocal laser scanning
      microscopy. Irregular fused cells gradually became spherical during culture, and
      nuclei and mitochondria were redistributed in the fused cell; nuclei formed a
      cluster surrounded by mitochondria. F-actin, vimentin, and microtubules were also
      reorganized with the redistribution of cell organelles. Further, when the
      morphological change was inhibited by L4-1, a chlorophyll-like substance derived
      from silkworm faeces, or pyropheophorbide-a, the arrangement of organelles and
      cytoskeleton remained disturbed, suggesting that the movement of the cytoskeleton
      is closely associated with cell shape and the distribution of cytoplasmic
      organelles.

PMID- 11991665
TI  - Changes in fused cells induced by hvj (sendai virus): relationship of
      morphological changes to endocytosis of the surface membrane.
AB  - Fused Ehlrich ascites tumor (EAT) cells induced by hemagglutinating virus of
      Japan (HVJ; Sendai virus) had an irregular shape, reflecting the shape of cell
      aggregates before fusion. During subsequent culture, the fused cells gradually
      took on a spherical form within 60 min. Examination of the fused cells revealed a
      vigorous endocytosis of the cell membrane during the morphological change. When
      EAT cells were treated with porphyrin derivatives, and the morphological change
      to a spherical form was inhibited, endocytosis of fused cells was also
      suppressed, suggesting that the change is closely associated with endocytotic
      activity. Further examination with porphyrin derivatives and hydrogen peroxide
      suggested that the inhibition of morphological change is due to the suppression
      of endocytosis by active oxygen species produced by these substances. Experiments
      using an endocytotic inhibitor, methylamine, indicated that endocytosis is
      essential for the morphological change that occurs in the fused cells.

PMID- 11991666
TI  - Does the bcr/abl-mediated increase in the efficacy of DNA repair play a role in
      the drug resistance of cancer cells?
AB  - BCR/ABL oncogenic tyrosine kinase is responsible for the pathogenesis of
      Philadelphia chromosome-positive human leukemia and is generated by a specific
      reciprocal chromosome translocation, t(9;22)(q34-;q11+). We examined the role of
      DNA repair in therapeutic drug resistance to idarubicin in the murine pro-B
      lymphoid cell line BaF3 and its BCR/ABL -transformed clone. These cells can be
      used as models of human leukemias. The MTT assay revealed that BCR/ABL 
      transformed cells displayed resistance to idarubicin in the range 0.3-0.5 microm,
      compared with the control BaF3 cells. Idarubicin at 0.3 and 1 microm induced DNA
      damage in the form of strand-breaks and/or alkali labile sites in both
      transformed and control cells in comet assays. The BCR/ABL -transformed cells
      needed only 60 min to remove damage to their DNA, whereas controls took 120 min.
      We hypothesize that this observed increase in the efficacy of repair in BCR/ABL-
      positive cells is involved in their resistance to idarubicin.

PMID- 11991667
TI  - The carboxy-terminus of protein 4.1r resembles Beta-tubulin.
AB  - The protein 4.1R is an isoform of a larger family of 4.1 proteins. It is known as
      a component of the plasma membrane skeleton, but it is also found at the
      centrosomes in interphase and mitosis. To investigate the properties of the
      carboxy terminal region of protein 4.1R, we raised antibodies against a peptide
      representing the last 14 amino acids of 4.1R. These antibodies crossreact with an
      epitope in beta-tubulin and stain the microtubule network by immunofluorescence.
      Furthermore, sequence comparison of the carboxy terminal 4.1R peptide sequence
      with tubulin reveals homology with a region at the end of helix 5 in beta
      tubulin, but not alpha-tubulin. A potential function of the 4.1R carboxy terminus
      in regulating the formation of microtubule networks is discussed.

PMID- 11991668
TI  - C-reactive protein levels are influenced by common IL-1 gene variations.
AB  - Elevated markers of systemic inflammation are associated with the development of
      acute coronary syndromes, but there is no current explanation for increased
      inflammation in overtly healthy individuals. The influence of genetic control of
      the inflammatory response on the observed variability is unknown. We studied the
      frequency of four polymorphisms in interleukin (IL) 1 genes, known to modulate
      inflammation, in 454 individuals undergoing coronary angiography and analysed
      their influence on plasma C-reactive protein (CRP) and fibrinogen levels. Females
      and smokers had higher levels of CRP than males (Pi = 0.001) and non-smokers (Pi
      = 0.001). Patients with genotype 2.2 for the IL-1B(+3954) polymorphism had twice
      the median CRP levels of patients who were genotype 1.1 (4.33 vs 2.01 mg/l; P =
      0.001). Patients with genotype 1.2 or 2.2 at the IL-1A(+4845) polymorphism also
      had higher median CRP (2.92 vs 2.05 mg/l, Pi = 0.023). In multivariate analyses,
      CRP levels remained significantly associated with IL-1 polymorphisms after
      adjustment for smoking, gender and age. Fibrinogen levels had similar
      associations with the IL-1 genotypes. These data indicate that IL-1 gene
      polymorphisms known to affect the inflammatory response are highly related to
      plasma levels of CRP and fibrinogen in patients referred for coronary
      angiography.

PMID- 11991669
TI  - Counter-antigen presentation: fibroblasts produce cytokines by signalling through
      HLA class II molecules without inducing T-cell proliferation.
AB  - Fibroblasts are known to express histocompatibility leukocyte antigen DR (HLA-DR)
      molecules on their cell surface upon stimulation with interferon gamma (IFN-
      gamma), while the exact roles of HLA-DR on fibroblasts remain undetermined. To
      understand the role of HLA-DR molecules on fibroblasts, we examined whether: (1)
      fibroblasts act as antigen presenting cells (APC) which activate helper T (Th)
      cells; and/or (2) fibroblasts are activated via HLA-II molecules by making a T
      cell receptor (TCR)-peptide-major histocompatibility complex (MHC) complex. We
      used Th(0) clone HT8.3, which recognizes an antigenic peptide (Ag53 p141-161) in
      the context of DRB1*1501, as well as IFN - gamma - treated and irradiated
      periodontal ligament fibroblasts (PDL) expressing DRB1*1501 molecules. When
      peptide-pulsed fibroblasts were co-incubated with HT8.3 treated by the protein
      synthesis inhibitor emetine, peptide-induced de novo expression of lymphokines
      and cell-surface molecules on T cells can be neglected. The antigen presenting
      capacity of these fibroblasts was evaluated by examining the proliferative
      responses of Th cells. Possible activation of fibroblasts by stimulation via HLA
      DR molecules was evaluated by quantitating secreted cytokines in the supernatants
      after 18-h culture with or without anti-HLA-DR monoclonal antibody (mAb) or
      emetine-treated HT8.3. Indeed, Th cells did not show proliferative responses when
      peptide-pulsed PDL were used as APC, whereas PDL produced larger amounts of
      interleukin (IL) 6, IL-8, monocyte chemoattractant protein 1 (MCP-1) and
      regulated upon activation, normal T expressed and secreted (RANTES) compared with
      controls, when cultured with anti-HLA-DR mAb or emetine-treated HT8.3. These
      findings suggest that HLA-DR expressed on fibroblasts do not present antigens to
      induce T-cell proliferation, but may act as receptor molecules that transmit
      signals into fibroblasts, based on DR-peptide-TCR interaction, resulting in the
      secretion of several cytokine species.

PMID- 11991670
TI  - Variations in transforming growth factor beta in human milk are not related to
      levels in plasma.
AB  - There is considerable variability in the concentrations of transforming growth
      factor beta (TGFbeta) in human milk from individual women which is not readily
      explained by maternal factors such as smoking or illness. A potential correlate
      is the maternal plasma level of TGFbeta since changes in plasma concentration of
      TGFbeta in response to a number of pathological conditions have been well
      documented. The purpose of this study was to investigate the relationship between
      the concentration of TGFbeta1 and TGFbeta2 in a single sample of human milk and
      plasma obtained on the same day from 80 lactating mothers at 5 weeks postpartum.
      The concentration of TGFbeta1 and TGFbeta2 in the aqueous fraction of human milk
      ranged from 228 to 3542 pg/ml (647, 438-799; median, 25th-75th percentiles) and
      98 to 13 855 pg/ml (955, 535-1999) respectively and in paired samples of plasma
      from 440 to 19 460 (4026, 3245-6656) and 92 to 1739 (620, 391-925) respectively.
      Thus, in milk the median ratio of TGFbeta1 to TGFbeta2 was 1:1.6 whereas the
      corresponding median ratio in plasma was 7:1. There was no correlation between
      the concentration of either isoform of TGFbeta in milk and the corresponding
      TGFbeta in plasma.

PMID- 11991671
TI  - Endogenous interferon-alpha production by differentiating human monocytes
      regulates expression and function of the IL-2/IL-4 receptor gamma chain.
AB  - In vitro monocyte-derived macrophages (MDMac) and synovial fluid macrophages from
      inflamed joints differ from monocytes in their responses to interleukin 4 (IL-4).
      While IL-4 can suppress LPS-induced interleukin beta (IL-beta) and tumour
      necrosis factor alpha (TNF-alpha) production by monocytes, IL-4 can suppress LPS
      induced IL-1 beta, but not TNFalpha production by the more differentiated cells.
      Recently we reported a correlation between the ability of IL-4 to regulate
      TNFalpha production by monocytes and the expression of the IL-4 receptor gamma
      chain or gamma common (gamma c chain). Like MDMac, interferon alpha (IFNalpha)
      treated monocytes expressed less IL-4 receptor gamma c chain, reduced levels of
      IL-4-activated STAT6 and IL-4 could not suppress LPS-induced TNFalpha production.
      In addition, like monocytes and MDMac, IFNalpha-treated monocytes expressed
      normal levels of the IL-4 receptor alpha chain and IL-4 significantly suppressed
      LPS-induced IL-1 beta production. With addition of IFNalpha-neutralizing
      antibodies, the ability of IL-4 to suppress LPS-induced TNFalpha production with
      prolonged monocyte culture was restored. Detection of IFNalpha in synovial fluids
      from inflamed joints further implicates IFNalpha in the inability of IL-4 to
      suppress TNFalpha production by synovial fluid macrophages. This study identifies
      a mechanism for the differential expression of gamma c and varied responses to IL
      4 by human monocytes compared with MDMac.

PMID- 11991672
TI  - Amiodarone inhibits interleukin 6 production and attenuates myocardial injury
      induced by viral myocarditis in mice.
AB  - A recent study has shown that amiodarone inhibits the production of cytokines in
      vitro. This study was performed to examine the effects of amiodarone on survival,
      heart weight-to-body-weight ratio (HW/BW), myocardial lesions and cytokines
      production in a murine model of viral myocarditis induced by the
      encephalomyocarditis virus (EMCV). Four-week-old male DBA/2 mice were inoculated
      with the EMCV. To examine its effect on survival and HW/BW on day 14, mice were
      administered oral amiodarone (30 mg/kg) or the vehicle only once daily, starting
      4 days before inoculation of the virus. The effects of amiodarone on
      histopathologic changes in myocardial lesions and myocardial cytokine production
      were studied in mice treated with amiodarone (10 mg/kg or 30 mg/kg) or vehicle,
      and killed day 7. The survival rate on day 14 was significantly higher in the
      amiodarone-treated mice than in the control mice. The HW/BW, histopathologic
      score of cellular infiltration and myocardial interleukin 6 concentration were
      significantly lower in the amiodarone-treated group than in the control group.
      Likewise, myocardial necrotic area was significantly smaller in the amiodarone
      group than in the control group. This study suggests that the beneficial effects
      of amiodarone in viral myocarditis may be mediated by decreasing interleukin 6
      production in myocardial tissue.

PMID- 11991673
TI  - Sequence and expression analysis of deer mouse interferon-gamma, interleukin-10,
      tumor necrosis factor, and lymphotoxin-alpha.
AB  - Deer mice (Peromyscus maniculatus) are the principal host species of Sin Nombre
      (SN) virus, the primary etiologic agent of hantavirus cardiopulmonary syndrome in
      North America. The disease is a cytokine-mediated immunopathology characterized
      by pulmonary mononuclear infiltrates without discernible viral pathology.
      Infected deer mice remain life-long carriers and virus is found in many organs,
      including the lungs, but without pathology. It is unclear how deer mice respond
      to SN virus because no tools exist to examine the immune response in infected
      animals. As an initial step in examining host responses to SN virus, we have
      cloned partial cDNAs of deer mouse interferon-gamma (IFN-gamma), interleukin-10
      (IL-10), tumor necrosis factor (TNF) and lymphotoxin-alpha (LTalpha). IL-10, TNF
      and LTalpha sequences are highly conserved compared to orthologs of other
      mammalian species, while IFN-gamma is substantially less conserved. Phylogenetic
      analyses indicate that the amino acid sequences of IFN-gamma and TNF may be
      useful in resolving relationships at the subfamily level within the rodent family
      Muridae. While all four sets of analyses were able to reconstruct clade Rodentia,
      they were not able to resolve the relationships among the mammalian orders
      represented in this study. Reverse transcriptase polymerase chain reaction (RT
      PCR) analysis of concanavalin A-stimulated splenocytes determined that maximal
      IFN-gamma and TNF expression occurred rapidly while IL-10 and LTalpha expression
      was maximal at 24 h.

PMID- 11991674
TI  - Different activities of type I interferons on hepatitis B virus core promoter
      regulated transcription.
AB  - The type I interferons (IFNs) are a group of closely related cytokines which have
      different signal transduction pathways and different biological activities. Using
      transient transfection of human hepatoma cells with reporter plasmids containing
      the firefly/renilla luciferase genes under the control of the HBV-Enhancer (Enh)
      I, Enh II and core promoter we have investigated the biological activities of 10
      recombinant (r) type I IFNs on transcription. Low concentrations of IFN (0.025
      ng/ml) had a significant and specific inhibitory effect but the potencies of the
      different recombinant type I IFNs differed markedly with IFNalpha8 and IFNbeta
      being six-fold more potent than the least effective subtype (IFNalpha1). However,
      the addition of IFNalpha5-the subtype produced predominantly in the human liver
      did not cause any synergistic effects.The non-natural consensus IFN displayed a
      more pronounced inhibition of HBV-regulated transcription than IFNalpha8 or
      IFNalpha2 but not IFNbeta. The INF-induced inhibitory effect was not dependent on
      the presence of the HBV-Enh1 and in particular of an interferon stimulated
      response element (ISRE)-like sequence. The characterization of different effects
      among type I interferons on HBV-regulatory elements may implicate an IFN-subtype
      specific role for the pathogenesis and treatment of HBV-infection.

PMID- 11991675
TI  - Production of IL-10, TNF-alpha, IFN-gamma, TGF-beta1 by different populations of
      erythroid cells derived from human embryonal liver.
AB  - It has previously been determined that erythroid cells of mice are capable of
      expressing such cytokines as interleukin (IL) 1 alpha and beta, IL-4, IL-6,
      interferon gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and transforming growth factor beta (TGF-beta). It has been shown that
      glycophorin A(+) (GlA(+)) and antigen erythroblasts (AG-EB(+)) (both human
      erythroid cells of embryonic origin) are also capable of producing a series of
      cytokines such as IL-1 beta, IL-2, IL-4 and IL-6. The aim of this work was to
      study the capacity of erythroid cells from human embryonic liver to produce such
      cytokines as IFN-gamma, TGF-beta1, tumour necrosis factor alpha (TNF-alpha) and
      IL-10. The erythroid cells were isolated by means of antibodies specific to
      erythroblasts (GlA and AG-EB), as well as those from single erythroid colonies.
      The production level of some cytokines varies insignificantly under the action of
      erythropoietin (Epo) and quantitatively differs in GlA(+) and AG-EB(+) erythroid
      cells. Hence, the erythroid cells express IFN-gamma, TGF-beta1, TNF-alpha and IL
      10. The erythroid cells could be involved through the production of these
      cytokines in the regulation of such processes as self-renewal, proliferation and
      differentiation of cells of other blood-forming sites.

PMID- 11991676
TI  - Clinical cancer research 2001: new agents and therapies.

PMID- 11991677
TI  - The role of pro-drug therapy in the treatment of cancer.
AB  - The administration of anti-cancer agents is currently associated with significant
      toxicity and lack of tumour specificity. Prodrugs are being designed to
      favourably alter the therapeutic index of these agents by improving their
      efficacy and reducing toxicity. Progress in the development of prodrugs including
      the cytotoxic agents most commonly used in cancer treatments namely 5
      fluorouracil (5-FU), the anthracyclines, paclitaxel and platinum will be
      described. Many of these agents are at an early stage of development: however,
      this article will also describe those which have already made an impact in the
      clinic. It is likely that future improvements in care will come from refinement
      of the drugs already well established in clinical practice. In addition, this
      technology could be applied to novel agents with alternative cellular targets
      such as those involved in angiogenesis or in conferring metastatic potential.
      Thus, lessons learned with standard drugs may be applicable across a wider
      spectrum of therapeutics.

PMID- 11991678
TI  - The role of Fas and FasL as mediators of anticancer chemotherapy.
AB  - Fas Ligand (FasL) is a member of the TNF superfamily that induces apoptosis in
      susceptible cells upon cross-linking of its own receptor, Fas (Apo-1/CD95). FasL
      induced apoptosis contributes to immune homeostasis and cell-mediated
      cytotoxicity. Several groups have suggested that it also participates in the
      mechanism of action of DNA-damaging anticancer drugs. However, others have
      disputed this hypothesis, based largely on the inability of exogenously added
      anti-Fas/FasL reagents to attenuate drug-induced apoptosis in their studies. In
      this minireview, we discuss the most recent evidence for and against the
      involvement of FasL/Fas in the sensitivity and resistance to chemotherapy in a
      variety of models. In our own model of Ewing's sarcoma (ES), we have extensively
      investigated the involvement of the FasL/Fas pathway in doxorubicin (Dox)-induced
      apoptosis. We have generated clones of the Fas-sensitive, Dox-sensitive ES cell
      line SK-N-MC that were either Fas-resistant or FasL-deficient, and found that
      they were significantly resistant to Dox. Cleavage of FasL by MMP-7 (matrilysin)
      protected the parental SK-N-MC cells from Dox, whereas inhibition of MMP-7
      activity increased their sensitivity. Transfection of a construct encoding
      soluble (decoy) Fas protected SK-N-MC cells from Dox. However, incubation with
      anti-Fas or anti-FasL neutralizing antibodies or exogenous addition of pre
      synthesized recombinant soluble Fas decoy protein had no protective effect. This
      raises the possibility that the proposed Fas/FasL suicidal interaction may take
      place in an intracellular compartment and thus is not accessible to exogenously
      added reagents. Therefore, commercially available Fas/FasL neutralizing reagents
      may not be a reliable indicator of the involvement of the Fas pathway in
      anticancer-drug-induced apoptosis and experiments using these agents should be
      carefully re-evaluated. The combined use of MMP inhibitors with conventional,
      cytotoxic chemotherapy may hold therapeutic benefit.

PMID- 11991679
TI  - Potential and caveats of TRAIL in cancer therapy.
AB  - Induction of apoptosis in tumor cells is a major goal for chemotherapy and
      radiation treatment strategies. However, disordered gene expression often leads
      to apoptosis resistance rendering tumor cells insensitive to various conventional
      treatments. TNF-related apoptosis-inducing ligand (TRAIL) is a recently
      identified cytokine of the TNF superfamily that induces apoptosis in tumor cells
      upon binding to different receptors. Remarkably, the majority of tumor cell lines
      are sensitive to TRAIL-induced apoptosis, while most nontransformed cell types
      are TRAIL-resistant. Furthermore, a combination treatment of TRAIL with ionizing
      irradiation or chemotherapeutic agents induces apoptosis in a highly synergistic
      manner, particularly in those cells that are otherwise resistant to a sole
      treatment. In contrast to other TNF members, TRAIL apparently does not exert
      overt systemic toxicity in murine and primate models, although unexpected
      concerns about a potential hepatotoxicity of TRAIL have been recently raised.
      While the molecular mechanisms of TRAIL sensitivity and resistance are poorly
      understood, TRAIL seems to be a promising biological agent for combination
      therapy with chemotherapeutic drugs or irradiation.

PMID- 11991680
TI  - Role of mitogen-activated protein kinases in the response of tumor cells to
      chemotherapy.
AB  - Antitumor agents, despite having diverse primary mechanisms of action, mediate
      their effects by inducing apoptosis in tumor cells. Cellular commitment to
      apoptosis, or the ability to evade apoptosis in response to damage, involves the
      integration of a complex network of survival and death pathways. Among the best
      characterized pathways regulating cell survival and cell death are those mediated
      by the mitogen-activated protein kinase (MAPK) family. Not surprisingly, MAPK
      signaling pathways have been implicated in the response of tumor cells to
      chemotherapeutic drugs. Indeed, literature in this area has grown enormously in
      recent years, and the present review attempts to provide an overview and
      perspective of these advances. While the activities of the major MAPK subgroups
      are subject to modulation upon exposure of different types of cancer cell lines
      to diverse classes of antitumor agents, the response tend to be context
      dependent, and can differ depending on the system and conditions. Despite these
      complexities, some important trends have surfaced, and molecular connections
      between MAPK signaling pathways and the apoptotic regulatory machinery are
      beginning to emerge. With increased evidence supporting a role for MAPK signaling
      in antitumor drug action, MAPK modulators may have potential as chemotherapeutic
      drugs themselves or as chemosensitizing agents. The ability of MAPK/ERK kinase
      (MEK) inhibitors to block survival signaling in specific contexts and promote
      drug cytotoxicity represents an example, and recent knowledge of the pro
      apoptotic functions of JNK and p38 suggests possible new approaches to targeted
      therapy. However, it will be important first to extrapolate the knowledge gained
      from these laboratory findings, and begin to address the role of MAPKs in the
      clinical response to chemotherapeutic drugs.

PMID- 11991681
TI  - Virus-mediated killing of cells that lack p53 activity.

PMID- 11991682
TI  - The role of caspase-8 in resistance to cancer chemotherapy.
AB  - Toxicity of chemotherapeutic agents against cancer cells is mediated through the
      initiation of programmed cell death. Apoptosis is an evolutionarily conserved
      cascade of intracellular proteolytic events propagated by a family of cysteine
      proteases called caspases. Many receptor- and non-receptor-mediated death signals
      induce apoptosis via activation of caspase-8 (FLICE/MACH). Mechanisms of tumor
      resistance to cytotoxic drugs through decreased apoptosis may occur by altered
      expression of caspase-8, upregulation of caspase-8 inhibitors like FLIP (FLICE
      like Inhibitory Protein), or sequestration of caspase-8 by Bcl-2. Modulation of
      caspase-8 and apoptosis may be a therapeutic strategy for sensitization of drug
      resistant malignancies to radiation or combination chemotherapy.

PMID- 11991683
TI  - Breast cancer response to paclitaxel in vivo.
AB  - Clinical trials using neoadjuvant (primary, preoperative) chemotherapy
      demonstrate that breast cancer reduction relates to survival. To date, no pre
      treatment pathologic, phenotypic, or genotypic tumor characteristics predict a
      patient's likely benefit from paclitaxel. This has led to pilot clinical studies
      that have attempted to identify whether early cellular responses in vivo can be
      used to predict the effectiveness of chemotherapy. A potential benefit of such
      predictive studies will be the ability to tailor specific therapeutic approaches
      to individual patients. Important issues surrounding this field include how to
      accurately measure and/or categorize the extent of tumor reduction, and how and
      when to assess breast cancer cellular responses in vivo. Preliminary data
      indicate that initial apoptotic responses are critical to tumor reduction, and
      that the timing of tumor samples for assessment of response is important.
      Although inherent complete resistance of breast cancer to paclitaxel occurs in a
      minority of patients, mechanisms of acquired or partial resistance require
      further study. However, the initial apoptotic response to paclitaxel has been
      shown to transiently reduce both cell density and intratumoral pressure,
      providing a window of time when there can be improved penetration of paclitaxel
      into the tumor. Thus a strong initial apoptotic response can set up a compounding
      benefit from subsequent treatments. Knowledge of breast cancer response to
      paclitaxel in vivo could lead to therapeutic strategies that enhance the
      apoptotic response and optimize the dosing schedule, to improve the tumor
      reduction for most patients.

PMID- 11991684
TI  - If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe
      in tumor cells.
AB  - Inhibition of the program of apoptosis has been reported to have little or no
      effect on clonogenic survival after treatment with drugs or radiation in several
      tumor cell lines. A decrease in apoptosis is compensated in such cell lines by an
      increase in the fractions of cells that undergo permanent growth arrest with
      phenotypic features of cell senescence, or die through the process of mitotic
      catastrophe. Most of the tested tumor cell lines have retained the capacity of
      normal cells to undergo accelerated senescence after treatment with DNA
      interactive drugs, ionizing radiation, or cytostatic agents. p53 and
      p21(Waf1/Cip1/Sdi1) act as positive regulators of treatment-induced senescence,
      but they are not required for this response in tumor cells. The senescent
      phenotype distinguishes tumor cells that survived drug exposure but lost the
      ability to form colonies from those that recover and proliferate after treatment.
      Although senescent cells do not proliferate, they are metabolically active and
      may produce secreted proteins with potential tumor-promoting activities. The
      expression of such proteins is mediated at least in part by the induction of
      p21(Waf1/Cip1/Sdi1). The other anti-proliferative response of tumor cells is
      mitotic catastrophe, a form of cell death that results from abnormal mitosis and
      leads to the formation of interphase cells with multiple micronuclei. Mitotic
      catastrophe is induced by different classes of cytotoxic agents, but the pathways
      of abnormal mitosis differ depending on the nature of the inducer and the status
      of cell-cycle checkpoints. Mitotic catastrophe can also develop as a consequence
      of aberrant reentry of tumor cells into cell cycle after prolonged growth arrest.
      Elucidation of the factors that regulate different aspects of treatment-induced
      senescence and mitotic catastrophe should assist in improving the efficacy and
      decreasing side effects of cancer therapy.

PMID- 11991685
TI  - Inhibition of tumor angiogenesis by non-steroidal anti-inflammatory drugs:
      emerging mechanisms and therapeutic perspectives.
AB  - Chronic intake of non steroidal anti-inflammatory drugs (NSAIDs) is associated
      with a reduced risk of developing gastrointestinal tumors, in particular colon
      cancer. Increasing evidence indicates that NSAID exert tumor-suppressive activity
      on pre-malignant lesions (polyps) in humans and on established experimental
      tumors in mice. Some of the tumor-suppressive effects of NSAIDs depend on the
      inhibition of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of
      prostaglandins and thromboxane, which is highly expressed in inflammation and
      cancer. Recent findings indicate that NSAIDs exert their anti-tumor effects by
      suppressing tumor angiogenesis. The availability of COX-2-specific NSAIDs opens
      the possibility of using this drug class as anti-angiogenic agents in combination
      with chemotheapy or radiotherapy for the treatment of human cancer. Here we will
      briefly review recent advances in the understanding of the mechanism by which
      NSAIDs suppress tumor angiogenesis and discuss their potential clinical
      application as anti-cancer agents.

PMID- 11991686
TI  - Are cytochrome b gene mutations the only cause of atovaquone resistance in
      Pneumocystis?
AB  - There is evidence that exposure of the opportunistic pathogen Pneumocystis to
      atovaquone enhances the development of resistance to the drug. Atovaquone is a
      structural analog of ubiquinone, which binds to the mitochondrial cytochrome
      bc(1) complex and inhibits electron transport. Like the parasites Plasmodium and
      Toxoplasma, atovaquone resistance can result from mutations in the cytochrome b
      gene of Pneumocystis. However, atovaquone resistance cannot be explained by
      cytochrome b gene mutations in all cases. The discovery that atovaquone also
      inhibits biosynthesis of ubiquinone in P. carinii may unfold other mechanisms by
      which drug resistance develops.

PMID- 11991687
TI  - Carotid artery disease and stroke during coronary artery bypass: a critical
      review of the literature.
AB  - OBJECTIVES: to determine the role of carotid artery disease in the
      pathophysiology of stroke after coronary artery bypass (CABG). DESIGN: systematic
      review of the literature. RESULTS: the risk of stroke after CABG was 2% and
      remained unchanged between 1970-2000. Two-thirds occurred after day 1 and 23%
      died. 91% of screened CABG patients had no significant carotid disease and had a
      <2% risk of peri-operative stroke. Stroke risk increased to 3% in predominantly
      asymptomatic patients with a unilateral 50-99% stenosis, 5% in those with
      bilateral 50-99% stenoses and 7-11% in patients with carotid occlusion.
      Significant predictive factors for post-CABG stroke included; (i) carotid bruit
      (OR 3.6, 95% CI 2.8-4.6), (ii) prior stroke/TIA (OR 3.6, 95% CI 2.7-4.9) and
      (iii) severe carotid stenosis/occlusion (OR 4.3, 95% CI 3.2-5.7). However, the
      systematic review indicated that 50% of stroke sufferers did not have significant
      carotid disease and 60% of territorial infarctions on CT scan/autopsy could not
      be attributed to carotid disease alone. CONCLUSIONS: carotid disease is an
      important aetiological factor in the pathophysiology of post-CABG stroke.
      However, even assuming that prophylactic carotid endarterectomy carried no
      additional risk, it could only ever prevent about 40-50% of procedural strokes.

PMID- 11991688
TI  - Duplex scan findings in patients with spontaneous cervical artery dissections.
AB  - AIM: to report duplex scan findings in patients with spontaneous internal carotid
      artery (ICA) or vertebral artery (VA) dissection. MATERIAL AND METHODS: the
      records of 24 patients (13 males and 11 females, median age 48 years [range 25-68
      years]) with spontaneous extracranial ICA dissection (n=20) or VA dissection
      (n=4), identified between January 1995 and December 1999, were retrospectively
      analysed. RESULTS: four different abnormal flow patterns were observed in
      patients with ICA dissection: (a) absence of flow (15%), (b) staccato flow (50%),
      (c) reduced flow velocity (25%) and, (d) stenotic flow (10%). B-mode ultrasound
      showed a homogenous echolucent lesion in eight patients and a double lumen in
      two. Staccato flow along the entire ICA was observed in only four patients
      without verified dissection during the study period. In the four patients with VA
      dissection, duplex scanning demonstrated staccato flow in three and reversed low
      amplitude pulsatile flow in one. CONCLUSION: duplex scanning is an important
      noninvasive diagnostic modality in patients with cervical artery dissection.
      Staccato flow along the extracranial ICA strongly indicates the presence of
      spontaneous ICA dissection.

PMID- 11991689
TI  - Neck irradiation: a risk factor for occlusive carotid artery disease.
AB  - OBJECTIVES: to determine whether irradiation is an independent risk factor for
      carotid atherosclerosis, and propose guidelines for patient follow-up. DESIGN: a
      retrospective case control study. MATERIALS AND METHODS: two groups of patients
      with severe carotid artery stenosis (>70%) were compared: 30 post-neck
      irradiation patients, and a control group of 100 patients with no history of neck
      irradiation. Disease location and severity were assessed by duplex. The
      relationship between atherosclerotic risk factors, time since irradiation and
      carotid artery disease was examined. RESULTS: the average age of study group
      patients was 67 years (43-86) compared to 69 years (46-89) in the control group.
      The average interval from irradiation to diagnosis was 14 years (3-53) (median
      12.5 years). The study group suffered less from diabetes, ischaemic heart
      disease, and peripheral vascular disease ( p<0.02). There were no significant
      differences among risk factors with respect to age, gender, smoking,
      hypertension, and hypercholesterolemia. Post-neck irradiation patients had a
      significantly higher prevalence of bilateral disease (p=0.02), and a higher rate
      of common carotid artery lesions (p<0.002). CONCLUSIONS: neck irradiation should
      be considered a risk factor for occlusive carotid artery disease. Preoperative
      angiographic study should be considered, due to frequent involvement of the
      common carotid artery.

PMID- 11991690
TI  - Endovascular approach to abdominal aortic aneurysms limits the postoperative
      systemic immune response.
AB  - OBJECTIVES: endovascular repair of abdominal aortic aneurysms (E-AAA) has in
      recent years developed as an alternative to the conventional open repair (C-AAA).
      Adverse outcomes following the open approach may relate to immune cell activation
      and the systemic inflammatory response syndrome (SIRS) and organ failure but the
      benefits in this respect of the endovascular approach are unclear. This study
      evaluated this question and focused on T-cell activation and function. DESIGN:
      prospective clinical study. MATERIALS: twenty patients undergoing abdominal
      aortic aneurysm repair (12 C-AAA and 8 E-AAA). METHODS: peripheral T-cell
      expression of surface markers CD69, CD62L and CD25 in vivo and Interleukin 2 (IL
      2) and Interleukin-10 (IL-10) responses to the superantigen staphylococcal
      enterotoxin B (SEB) in vitro were measured preoperatively, 24 h and 1 week
      postoperatively. RESULTS: there was no significant increase (p=0.23) in the
      incidence of SIRS in the open compared with the endovascular group. Enhanced T
      cell activation occurred following C-AAA and this was associated with
      significantly greater IL-2 production in response to SEB, with no change in IL-10
      production. CONCLUSIONS: E-AAA attenuates proinflammatory T-cell changes compared
      with C-AAA repair. A reduction in T-cell activation and impaired responsiveness
      to superantigen suggests that the immunological sequelae of the endovascular
      approach to aneurysm repair is more favourable than after the open approach with
      potentially less risk of adverse outcomes. Proof of this thesis will require a
      larger prospective study.

PMID- 11991691
TI  - Exercise training reduces the acute inflammatory response associated with
      claudication.
AB  - BACKGROUND: recent research has shown that episodes of claudication may be
      associated with a systemic inflammatory response that causes injury to the
      vascular endothelium. As claudicants are often directed to undertake regular
      walking exercises there has been a concern that this may accelerate endothelial
      injury. AIMS: the aim of our study was to assess the baseline markers of
      ischaemia-reperfusion injury (IRI) in claudicants and controls after acute
      treadmill exercise and to then examine the effect of a 3 month supervised
      exercise-training programme, on these markers, in the claudicant group. METHODS:
      forty-six claudicants and 22 age-matched controls undertook acute treadmill
      exercise. Neutrophil activation, degranulation, free radical damage and
      antioxidants were measured (by flow cytometry, ELISA, and chemiluminescence) at
      rest and at 5, 30 and 60 min post-exercise. Claudicants were then recruited into
      an intensive 3 month supervised exercise programme (SEP) after which the same
      parameters of IRI were reassessed at different time points, at 3 and 6 months.
      RESULTS: resting markers of IRI were similar in both groups. Exercise had no
      effect on the control group. Immediately after exercise, claudicants developed
      significant neutrophil activation and degranulation with free radical damage.
      This effect decreased sequentially after 3 months of exercise training.
      CONCLUSION: this study for the first time demonstrates that the exercise training
      of claudicants is beneficial, not only in terms of improving their walking
      distance, but also by decreasing the injurious effects of IRI that occur during
      claudication. Exercise training should be an essential part of the medical
      management of the majority of claudicants.

PMID- 11991692
TI  - The role of pedometers in the assessment of intermittent claudication.
AB  - OBJECTIVES: to evaluate the role of pedometers in the assessment of patients with
      intermittent claudication by comparing them with treadmill testing, post-exercise
      ankle brachial pressure index (ABPI) and physical function questionnaires.
      PATIENTS AND METHODS: fifty patients with intermittent claudication were
      prospectively assessed by treadmill examination measuring maximum walking
      distance (MWD) and post-exercise ABPI. Three physical function questionnaires:
      (1) Medical Outcome Study Short Form-36 (MOS SF-36), Physical Function (PF). (2)
      MOS SF-36 Role limitation due to Physical Problems (RP). (3) Walking Impairment
      Questionnaire (WIQ) were completed. Pedometers were used for one week and the
      daily average number of steps taken by each patient recorded. Pedometers scores
      were compared with MWD, post-exercise ABPI and physical function questionnaires
      scores using Spearman correlation test. RESULTS: pedometers estimation of daily
      physical activity moderately correlated with MWD (Rho=0.35, p=0.01), post
      exercise ABPI (Rho=0.35, p=0.01), MOS-SF 36 PF (Rho=0.31, p=0.02), MOS-SF RP
      (Rho=0.28, p=0.05) and with WIQ (Rho=0.42, p=0.003). CONCLUSIONS: they moderately
      correlate with treadmill testing, post-exercise ABPI, and with physical function
      questionnaires. Pedometers may provide a simple and cheap alternative for the
      assessment of physical and functional disability in intermittent claudication.

PMID- 11991693
TI  - Skin closure after infrainguinal bypass surgery: a prospective randomised study.
AB  - BACKGROUND AND PURPOSE: wound complications after infrainguinal bypass surgery
      occur frequently and may jeopardise an underlying graft. The purpose of this
      study was to investigate the role of suture material in the occurrence of wound
      complications. METHODS: prospective randomised trial. 170 consecutive patients
      underwent femoro-popliteal or femoro-tibial bypass surgery and were randomised
      between wound closure with continuous polyamide sutures (Ethilon) or with skin
      staples. RESULTS: ten patients were excluded because of re-intervention or death
      within 2 weeks after operation. The wound was closed with a continuous polyamide
      suture (Ethilon) in 77 patients and with metallic skin staples in 83 patients.
      The groups were comparable in age, use of corticosteroids, occurrence of diabetes
      mellitus and operation time. Skin closing time was significantly shorter in the
      staples group (6.4 min versus 2.7 min, p<0.001). Overall, there were no
      significant differences between continuous polyamide sutures and metallic skin
      staples in superficial infections (8% versus 2%), deep infections (1% versus 1%),
      serous leakage or haematoma. CONCLUSION: we found no significant differences in
      the incidence of wound complications in infrainguinal bypass surgery comparing
      continuous polyamide (Ethilon) and skin staples. The time needed for wound
      closure was significantly reduced using metallic staples, but this had no effect
      on the total operation time. Choices of closing materials should be guided by
      surgeon's preference.

PMID- 11991694
TI  - Methylene blue soldered microvascular anastomoses in vivo.
AB  - OBJECTIVES: solders containing chromophores and proteins enhance the strength of
      lasered anastomoses. Methylene blue (MB) solder anastomoses in vitro are strong
      but no in vivo work has been reported. We used an MB solder in vivo and studied
      the effects of two laser powers on patency and histological appearance. DESIGN,
      MATERIALS AND METHODS: two groups of 15 rabbits had unilateral end-to-end carotid
      anastomoses (1.5-2.0 mm) formed using three stay sutures and MB solder. Group 1
      anastomoses were formed at 5.7 Wcm(-1) and Group 2 at 2.8 Wcm(-1). The vessels
      were examined at various points by necropsy for patency and gross macroscopic
      appearance, with subsequent histological examination. RESULTS: group 2 showed
      patency of 93.3% v 0% ( p<0.001) endothelialisation of 100% v 26.6% ( p<0.001),
      giant cell formation 0% v 40.0% ( p<0.01), but stenosis was not significantly
      different (0% v 13.3% p=0.06). Group 2 showed a higher rate of intimal
      hyperplasia (IH) (66.6% v 20.0% p<0.05) but neither group exhibited thermal
      injury or aneurysm formation. CONCLUSIONS: laser soldered microvascular
      anastomoses were formed in vessels of 1.5-2.0 mm with a high degree of patency. A
      relationship appears to exist between laser power and anastomotic patency.
      Methylene blue fading has the potential to act as a switch against over exposure
      and a visual indicator of solder activation.

PMID- 11991695
TI  - Duplex follow-up of aorto-iliac stents.
AB  - OBJECTIVES: to assess the feasibility of duplex follow up of aorto-iliac stents.
      MATERIAL AND METHODS: in addition to standard clinical and ankle/brachial
      pressure assessment, 75 patients undergoing aorto-iliac stenting for
      atherosclerotic disease were prospectively followed up with duplex ultrasound at
      3 monthly interval up to 1 year and then annually. We attempted to directly
      visualise the stents wherever possible using standard 2D imaging, standard and
      power Doppler, as well as spectral Doppler. Patients had an angiogram at 12
      months or sooner if a problem was identified on the duplex scan. RESULTS: mean
      follow up was 14 months (2-36). Complete visualisation of the pelvic arterial
      tree was achieved in 94% of scans. All patients had at least one satisfactory
      scan. Duplex detected 30 lesions in 23 patients. Twenty-seven lesions were
      confirmed at angiography. There were two false positives. Overall sensitivity,
      specificity and accuracy were 100%, 93% and 96% for patient undergoing
      angiography. CONCLUSION: duplex ultrasound follow up is feasible in the majority
      of patients.

PMID- 11991696
TI  - Randomised trial of pre-operative colour duplex marking in primary varicose vein
      surgery: outcome is not improved.
AB  - OBJECTIVE: the ability of colour duplex to accurately locate incompetent venous
      sites has been widely published; its value in pre-operative marking in simple
      primary varicose vein surgery is evaluated in this study. DESIGN OF STUDY:
      prospective randomised controlled trial. SETTING: regional vascular service,
      hospital patients. SUBJECTS: consecutive patients (149) undergoing primary
      varicose vein surgery where the only difference was one group of patients
      received duplex marking prior to surgery. Six weeks and 12 months post
      operatively all patients had a colour duplex scan to determine the accuracy of
      surgery and the presence of residual/recurrent varicose veins and completed the
      Aberdeen, SF-36, and EuroQol quality of life questionnaires. INTERVENTIONS:
      varicose vein surgery. MAIN OUTCOME MEASURES: Duplex evidence of venous
      incompetence, quality of life measures using the SF-36 and Aberdeen Varicose
      Veins Questionnaire. RESULTS: pre-operative marking of primary varicose veins by
      skilled duplex ultrasonography does not improve the accuracy or recurrence rate
      following surgery. Quality of life improved significantly following surgery in
      both groups, however there was no difference in this improvement between the
      groups. CONCLUSION: the trial has not demonstrated any additional benefit of pre
      operative colour duplex marking over that of clinical and hand held Doppler
      marking in terms of satisfactory varicose vein surgery performance at 6 weeks or
      12 months in patients with primary varicose veins of the long saphenous system.
      It role in the short saphenous system is less clear.

PMID- 11991697
TI  - Early thrombus remodelling of isolated calf deep vein thrombosis.
AB  - OBJECTIVE: this prospective study was designed to evaluate the evolution of
      thrombus propagation and lysis in relation to patterns and distribution of
      isolated calf DVT. METHODS: fifty-two limbs in 48 patients mean age 59+/-15,
      range 24-78 years, with isolated calf DVT that had at least one exam within 10
      days of DVT detection were included in the study. Patients with a documented
      episode of prior DVT or evidence of post-thrombotic changes during the initial
      ultrasound exam were excluded. The initial thrombus length, patterns and location
      of the thrombi were recorded. On follow-up the propagation and lysis patterns of
      the clot were studied. RESULTS: remodelling of the thrombus, excluding
      echotexture and vein diameter changes on ultrasound, occurred in 23 limbs, (44%).
      Ascending propagation only was seen in seven limbs (13%) descending propagation
      only in two (4%) and in both directions in five (10%). Propagation at least to
      popliteal vein was detected in seven limbs (13%). Thrombus developed or extended
      to initially uninvolved veins in six limbs (12%). Pulmonary embolism developed
      only in one patient (2%; 95% CI: 0-11%). The site and the size of thrombus or the
      number of veins involved in the baseline exam did not correlate with the
      remodeling of thrombus. Soleal and gastrocnemial veins were comparable with the
      posterior tibial and peroneal veins in terms of thrombus propagation and lysis.
      CONCLUSIONS: early thrombus remodelling occurs in 44% of limbs with isolated calf
      DVT. This includes ascending and descending thrombus propagation and lysis.
      Thrombus development or propagation to initially uninvolved calf veins is found
      in 12%. Thrombus remodelling does not appear to be related to size, site and
      patterns of thrombosis.

PMID- 11991698
TI  - A reduction in serum cytokine levels parallels healing of venous ulcers in
      patients undergoing compression therapy.
AB  - INTRODUCTION: vascular endothelial growth factor (VEGF) and tumour necrosis
      factor alpha (TNF(alpha)) have been specifically implicated in the tissue damage
      associated with chronic venous disease (CVD). Furthermore, production of both
      factors is known to be upregulated in vessel wall cells subject to hypertension.
      The aim of this study was to determine the local venous levels of VEGF and
      TNF(alpha) in limbs with venous ulcers before and after treatment with graduated
      compression. PATIENTS AND METHODS: eight patients with venous ulcers and 8
      patients with varicose veins only were included in the study. For ulcer patients,
      serum samples were taken from the superficial veins in lower limbs and repeated
      after 4 weeks of treatment with 4-layered graduated compression. Serum from the
      arms of the same patients served as controls. Determination of the concentrations
      of VEGF and TNF(alpha) proteins were performed with sandwich enzyme-linked
      immunosorbent assays. RESULTS: both groups of patients had elevated levels of
      VEGF and TNF(alpha). In patients with venous ulcers there was a reduction in the
      levels of both cytokines to below control values with treatment. These changes
      correlated with healing of the ulcers as determined by reduction in ulcer size.
      CONCLUSION: these data, for the first time, suggest a central role for both
      TNF(alpha) and VEGF in the pathogenesis of venous ulceration which may constitute
      a causative link between venous hypertension and tissue pathology.

PMID- 11991699
TI  - The Danish specialist training in vascular surgery.
AB  - OBJECTIVE: to present the Danish training in vascular surgery compared with other
      European countries. METHODS: analysis of prospectively collected data. Data on
      number of procedures and supervision was obtained from the Danish Vascular
      Registry for eighteen trainees (fifteen males, three females) in vascular
      surgery. Demographic data were obtained by direct contact with the units and from
      EuReg-Vasc. Vascular surgery has been a mono-specialty in Denmark since 1983.
      RESULTS: in 2000 the median age of the 45 Danish vascular specialists was 48
      years (IQR 45-54, range 40-58) and at end of training the age of the 18 vascular
      trainees was 42 years (IQR 40-43, range 38-51). Vascular surgery was confined to
      eleven vascular units - eight with trainees. All vascular procedures in Denmark,
      besides a few emergency cases, were performed at these units - all by vascular
      specialists or trainees. The 18 trainees were on average exposed to more than 400
      surgical procedures over the three years - and over 300 of nine vascular index
      operations. The number of assisted, supervised and independent operations was
      unevenly distributed, with low numbers of certain index operations for some of
      the trainees. CONCLUSION: the structure of vascular surgery in Denmark as a mono
      specialty has almost found its final form. Training is satisfactory overall, but
      with unacceptable variation among trainees with regard to the number of performed
      index procedures. A minimum number of index procedures must be defined and
      logbooks introduced. The relatively short weekly working hours in Denmark is not
      the prime problem.

PMID- 11991700
TI  - The early effect of lipid-lowering treatment on carotid and femoral intima media
      thickness (IMT).
AB  - OBJECTIVES: an increased intima media thickness (IMT) is an early indicator of
      the atherosclerotic process. We investigated the early effect of atorvastatin on
      the common carotid artery (CCA) and common femoral artery (CFA) IMT. METHODS: the
      IMT was measured in the CCA and the CFA of hyperlipidaemic patients referred with
      peripheral vascular disease. The measurements were performed using an automated
      radio frequency IMT technique pre-treatment and at 4 and 8 weeks post-treatment
      with 20 mg/day atorvastatin. RESULTS: patients (14 men; 11 women), median age 69
      years (range: 48-81) had a CCA-IMT mean (SD) of 0.79 (0.21) mm pre-treatment,
      0.75 (0.22) mm after 4 weeks, and 0.64 (0.15) mm after 8 weeks. The ANOVA test
      was significant (p=0.024) for the CCA-IMT trend. The corresponding CFA-IMT
      readings were 0.83 (0.13) mm, 0.80 (0.09) mm and 0.69 (0.14) mm (p=0.0003). After
      8 weeks of treatment there was a significant reduction in total cholesterol 6.0
      (0.3) to 4.3 (0.8) mmol/l, p=0.0004 and low-density lipoprotein cholesterol 3.7
      (0.2) to 2.2 (0.5), p=0.0001. There was a significant decrease in median serum
      creatinine levels after 8 weeks treatment: 87 micromol/l (range 67-114) to 84
      micromol/l (range: 64-112), p=0.007. CONCLUSIONS: cholesterol-lowering with
      atorvastatin 20 mg/day leads to a decrease in CCA-IMT and CFA-IMT. This
      difference achieved significance after 8 weeks of treatment, but a trend was
      visible at 4 weeks. These rapid changes in IMT may be attributable to an anti
      inflammatory effect. IMT measurement may be a useful tool to rapidly assess the
      effect of drug treatment on the atherosclerotic process.

PMID- 11991701
TI  - Endovascular repair of multiple peripheral aneurysms via a dual approach
      involving a venous graft conduit.

PMID- 11991702
TI  - Severe vaginal bleeding treated with a stent graft.

PMID- 11991703
TI  - A modification to the standard technique for carotid endarterectomy allowing
      removal of intact endarterectomy specimens: implications for research and quality
      control of preoperative imaging.

PMID- 11991705
TI  - Acute iliac stent thrombosis - an unusual complication following use of the Lloyd
      Davies position.

PMID- 11991704
TI  - Mobile carotid artery thrombus: is it a surgical emergency?

PMID- 11991706
TI  - Complete external iliac artery occlusion in a 34-year-old cyclist.

PMID- 11991707
TI  - Fatal case of accidental intra-arterial phenytoin injection.

PMID- 11991708
TI  - Bridging the divide.

PMID- 11991709
TI  - Unique genetic variation revealed by a microsatellite polymorphism survey in ten
      wild-derived inbred strains.
AB  - Here we report on a genome polymorphism survey using 254 microsatellite markers
      in ten recently wild-derived inbred strains. Allele size analysis showed that the
      rate of polymorphism of these wild-derived mouse strains when compared with any
      of the common laboratory strains is on average 79.8%. We found 632 wild-derived
      alleles that were not present in the common laboratory strains, representing a
      61% increase over the genetic variation observed in the laboratory strains. We
      also found that on average 14.5% of the microsatellite alleles of any given wild
      derived inbred strain were unique. Our results indicate that the recently wild
      derived mouse strains represent repositories of unique naturally occurring
      genetic variability and may prove invaluable for the study of complex phenotypes
      and in the construction of new mouse models of human disease.

PMID- 11991710
TI  - A class III myosin expressed in the retina is a potential candidate for Bardet
      Biedl syndrome.
AB  - Class III myosins are actin-based motors with amino-terminal kinase domains.
      Expression of these motors is highly enhanced in retinal photoreceptors. As
      mutations in the gene encoding NINAC, a Drosophila melanogaster class III myosin,
      cause retinal degeneration, human homologs of this gene are potential candidates
      for human retinal disease. We have recently reported the cloning of MYO3A, a
      human myosin III expressed predominantly in the retina and retinal pigmented
      epithelium [1]. The map locus of MYO3A is close to, but does not overlap, that of
      human Usher's 1F [2]. Here we introduce a shorter class III myosin isoform,
      MYO3B, which is expressed in the retina, kidney, and testis. We describe the cDNA
      sequence, genomic organization, and splice variants of MYO3B expressed in the
      human retina. A product of 36 exons, MYO3B has several splice variants containing
      either one or two calmodulin binding (IQ) motifs in the neck domain and one of
      three predominant tail variations: a short tail ending just past the second IQ
      motif, or two alternatively spliced longer tails. MYO3B maps to 2q31.1-q31.2, a
      region that overlaps the locus for a Bardet-Biedl syndrome (BBS5) linked to
      markers at 2q31 [3].

PMID- 11991711
TI  - The misidentification of bacterial genes as human cDNAs: was the human D-1 tumor
      antigen gene acquired from bacteria?
AB  - The initial analysis of the draft copy of the human genome sequence revealed the
      presence of several genes that were proposed to have been directly transferred
      from bacteria. We investigated the human D-1 antigen as a potential lateral
      transfer event. We report that although the human D-1 antigen seems to be an
      excellent candidate for lateral transfer, it is a contaminating bacterial
      sequence present in a human cDNA library that was included in the human genome
      analysis. Furthermore, several other genes present in the publicly available
      databases that were included in the analysis of the human genome are also likely
      contaminating bacterial sequences present in cDNA libraries.

PMID- 11991712
TI  - Many human genes are transcribed from the antisense promoter of L1
      retrotransposon.
AB  - Human L1 retrotransposon has two transcription-regulatory regions: an internal or
      sense promoter driving transcription of the full-length L1, and an antisense
      promoter (ASP) driving transcription in the opposite direction into adjacent
      cellular sequences yielding chimeric transcripts. Both promoters are located in
      the 5'-untranslated region (5'-UTR) of L1. Chimeric transcripts derived from the
      L1 ASP are highly represented in expressed-sequence tag (EST) databases. Using a
      bioinformatics approach, we have characterized 10 chimeric ESTs (cESTs) derived
      from the EST division of GenBank. These cESTs contained 3' regions similar or
      identical to known cellular mRNA sequences. They were accurately spliced and
      preferentially expressed in tumor cell lines. Analysis of the hundreds of cESTs
      suggests that the L1 ASP-driven transcription is a common phenomenon not only for
      tumor cells but also for normal ones and may involve transcriptional interference
      or epigenetic control of different cellular genes.

PMID- 11991713
TI  - An evaluation of the assembly of an approximately 15-Mb region on human
      chromosome 13q32-q33 linked to bipolar disorder and schizophrenia.
AB  - The human 13q32-q33 region has been linked to both bipolar disorder and
      schizophrenia. Before completion of the draft sequences, we developed an
      approximately 15-Mb comprehensive map for the region extending from D13S1300 to
      ATA35H12. This map was assembled using publicly available mapping data and
      sequence-tagged site (STS)-based PCR confirmation. We then compared this map with
      the NCBI, Celera Genomics, and UCSC Golden Path data in February, June, and
      September 2001. All data sets showed gaps, misassignment of STSs, and errors in
      orientation and marker order. Surprisingly, the completed sequences of many
      bacterial artificial chromosomes (BACs) had been truncated. Of 21 gaps that were
      detected, 4 were present in both the NCBI and Celera databases. All gaps could be
      filled using 1-2 BAC clones. A total of 39 loci mapped to additional sites within
      the human genome, providing evidence of segmental duplications. Additionally, 61
      unique cDNA clones were sequenced to increase available transcribed sequence, and
      11,353 reference single-nucleotide polymorphisms (SNPs) with an average density
      of 1 SNP/3720 bases were identified. Overall, integration of the data from
      multiple sources is still needed for complete assembly of the 13q32-q33 region.
      (c)

PMID- 11991714
TI  - Search for genes positively selected during primate evolution by 5'-end-sequence
      screening of cynomolgus monkey cDNAs.
AB  - It is possible to assess positive selection by using the ratio of K(a)
      (nonsynonymous substitutions per plausible nonsynonymous sites) to K(s)
      (synonymous substitutions per plausible synonymous sites). We have searched
      candidate genes positively selected during primate evolution by using 5'-end
      sequences of 21,302 clones derived from cynomolgus monkey (Macaca fascicularis)
      brain cDNA libraries. Among these candidates, 10 genes that had not been shown by
      previous studies to undergo positive selection exhibited a K(a)/K(s) ratio > 1.
      Of the 10 candidate genes we found, 5 were included in the mitochondrial
      respiratory enzyme complexes, suggesting that these nuclear-encoded genes
      coevolved with mitochondrial-encoded genes, which have high mutation rates. The
      products of other candidate genes consisted of a cell-surface protein, a member
      of the lipocalin family, a nuclear transcription factor, and hypothetical
      proteins.

PMID- 11991715
TI  - Cloning and characterization of Igsf9 in mouse and human: a new member of the
      immunoglobulin superfamily expressed in the developing nervous system.
AB  - We describe the cloning and characterization of a novel member of the
      immunoglobulin superfamily, Igsf9. The predicted protein structure of IGSF9
      closely matches that of the neural cell-adhesion molecule (NCAM) subfamily,
      consisting of an extracellular region containing five immunoglobulin domains and
      two fibronectin type III (FnIII) repeats, a transmembrane region, and a
      cytoplasmic tail. We have also characterized the orthologous human IGSF9 gene at
      1q22-q23, revealing a highly conserved sequence and genomic organization.
      Expression of Igsf9 was detected by RT-PCR in mouse embryonic RNA from embryonic
      day (E) 7.5 to E16.5, while whole-mount in situ hybridization at E10.5 shows
      intense expression within the dorsal root ganglia, trigeminal ganglia, and
      olfactory epithelium, and less intense expression in the neuroepithelium, retina,
      and hindgut. In the human, transcription was detected in a wide variety of fetal
      tissues at both 8 and 14 weeks. Protein homology of IGSF9 is most similar to the
      Drosophila melanogaster Turtle protein that functions in coordinated motor output
      in complex behaviors.

PMID- 11991716
TI  - A partial transcriptome of human epidermis.
AB  - Serial analysis of gene expression (SAGE) is a powerful technique for global
      expression profiling without prior knowledge of the genes of interest. We carried
      out SAGE analysis of purified keratinocytes derived from human skin biopsy
      specimens, resulting in a partial transcriptome of human epidermis. We identified
      7645 unique SAGE tags with quantitative information from 15,131 collected SAGE
      tags obtained from approximately 3 x 10(6) epidermal cells. This catalog contains
      a large number of genes that were not previously known to be expressed by human
      epidermis. Comparison with the databases of all known human SAGE tags allowed us
      to identify a number of keratinocyte-specific tags that putatively correspond to
      formerly unknown genes. Surprisingly, human epidermal keratinocytes in vivo show
      relatively low expression levels of genes typically associated with epidermal
      differentiation, whereas the expression levels of housekeeping genes are
      considerably higher than in cultured keratinocytes. This study provides a first
      step toward a transcriptome of human epidermis and, as such, harbors a wealth of
      information to identify genes involved in skin function, and candidate genes for
      genetic skin disorders.

PMID- 11991717
TI  - Naturally occurring variation in cardiovascular traits among inbred mouse
      strains.
AB  - The objective of this study was to characterize genetic variation in complex
      cardiovascular traits in two commonly used inbred mouse strains. We performed
      echocardiography, graded treadmill exercise, tail cuff plethysmography, and
      telemetry (heart rate, activity, temperature) in age- ( approximately 9 weeks)
      and sex-matched A/J and C57BL/6J (B6) inbred mice. B6 mice had significantly
      larger end-diastolic dimension (3.31+/-0.42 mm versus 2.83+/-0.31 mm) and left
      ventricle mass (46.2+/-14.1 versus 32.7+/-11.5 g) than A/J mice. This relative
      hypertrophy was eccentric (relative wall thickness ratios: 0.30+/-0.01 versus
      0.32+/-0.01) and was not associated with a difference in systolic blood pressure
      (122.0+/-13.2 versus 123.1+/-20.8 mmHg). Left ventricle fractional shortening
      (39.1+/-6.2 versus 47.1+/-6.9%) and heart rate (433+/-55 versus 524+/-45 beats
      per minute) were significantly lower in B6 versus A/J, respectively, resulting in
      similar resting echocardiographic cardiac indices (0.58+/-0.19 versus 0.50+/-0.17
      ml/min/g). Maximum exercise time on a treadmill was significantly greater in B6
      than in A/J mice (9.6+/-3.4 versus 4.4+/-1.9 minutes). Telemetry showed that body
      temperature was generally greater and heart rate lower in B6 than A/J; the
      relation with activity was more complex. These data suggest that relative to A/J,
      B6 mice have a phenotype characteristic of the "athlete's heart," that is,
      eccentric, physiologic hypertrophy, slower heart rates, and increased exercise
      endurance. This systematic characterization of functionally related
      cardiovascular traits in A/J and C57BL/6J mice revealed numerous differences
      whose genetic bases can be dissected with recombinant inbred, recombinant
      congenic, and chromosome substitution strains.

PMID- 11991718
TI  - A novel, brain-specific mouse drebrin: cDNA cloning, chromosomal mapping, genomic
      structure, expression, and functional characterization.
AB  - Drebrin A, a major neuronal actin-binding protein, regulates the dendritic spine
      shapes of neurons. Here, we have cloned and characterized a novel mouse cDNA
      clone encoding a truncated form of drebrin A, named s-drebrin A. Analysis of the
      genomic organization of the mouse drebrin gene (Dbn1), which mapped to the
      central portion of chromosome 13, revealed that isoforms including s-drebrin A
      are generated by alternative splicing from a single drebrin gene. The s-drebrin A
      mRNA was expressed in the brain, but not in non-neuronal tissues. The s-drebrin A
      expression was barely detected in the embryonic brain, but was upregulated during
      postnatal development of the brain. Overexpression of GFP-tagged s-drebrin A in
      fibroblasts showed it to be associated with actin filaments and with changes in
      actin cytoskeleton organization. These findings suggest that s-drebrin A has a
      role in spine morphogenesis, possibly by competing the actin-binding activity
      with drebrin A.

PMID- 11991719
TI  - Cloning and characterization of a novel apolipoprotein A-I binding protein, AI
      BP, secreted by cells of the kidney proximal tubules in response to HDL or ApoA
      I.
AB  - Apolipoprotein A-I (apoA-I) is the major apolipoprotein of high-density
      lipoproteins (HDL) and has an important role in the regulation of the stability,
      lipid transport, and metabolism of HDL particles. To identify novel proteins that
      are involved in HDL metabolism, we used mature apoA-I (amino acids 25-267) as a
      bait for the screening of a human liver two-hybrid cDNA library. Among the
      identified genes, several encoded known proteins, including serum amyloid A(2a)
      (SAA(2a)), apoC-I, and phosphodiesterase HCAM1 (PDE1A), found to interact with
      apoA-I. In addition, we have cloned a novel 29 kDa apoA-I interacting protein,
      which we named AI-BP (apoA-I binding protein). The AI-BP encoding gene, APOA1BP,
      which is located on chromosome 1q21, is composed of six exons and five introns
      and spans 2.5 kb. Northern blot analysis demonstrated ubiquitous expression of
      the APOA1BP mRNA with the highest expression in kidney, heart, liver, thyroid
      gland, adrenal gland, and testis. AI-BP protein is not detectable in serum of
      healthy probands, but serum samples of patients with septic syndromes may contain
      elevated levels of AI-BP. Significant amounts of AI-BP protein are found in
      cerebrospinal fluid and urine of healthy probands. The stimulation of cells
      derived from the kidney proximal tubules with apoA-I or HDL induces a
      concentration-dependent secretion of AI-BP indicating an important role for AI
      BP, in the renal tubular degradation or resorption of apoA-I.

PMID- 11991720
TI  - Identification of EPSTI1, a novel gene induced by epithelial-stromal interaction
      in human breast cancer.
AB  - During growth, invasion, and metastasis, tumor cells interact extensively with
      the surrounding stroma. To identify genes that are upregulated during this
      process, we compared mRNA pooled from tumor cells and fibroblasts cultured
      separately to mRNA from cells in coculture. Using differential display (DD), a
      transcript representing a novel gene, designated epithelial-stromal interaction 1
      (breast) (EPSTI1), was identified. EPSTI1 showed no homology to any known gene,
      but matched a cluster of expressed-sequence tags (ESTs). The full-length cDNA of
      1508 bp was generated by 5'-RACE, included an open reading frame (ORF) encoding a
      putative 307-amino-acid protein, and mapped to chromosome 13q13.3. EPSTI1 was
      highly upregulated in invasive breast carcinomas compared with normal breast. In
      a tissue mRNA panel the most prominent expression of EPSTI1 was found in
      placenta. Thus, EPSTI1 is a novel human gene expressed in tissues characterized
      by extensive epithelial-stromal interaction, and expression of this gene may be a
      crucial event in invasion and metastasis of cancer.

PMID- 11991721
TI  - Obox, a family of homeobox genes preferentially expressed in germ cells.
AB  - We used in silico (electronic database) subtraction to identify ESTs that are
      preferentially expressed in the adult mouse germ cells. During our analysis, we
      identified Obox1 and Obox2 transcripts as preferentially expressed in the mouse
      unfertilized egg libraries. Obox1 and Obox2 transcripts encode homeodomain
      proteins of 204 amino acids that share 97% identity with each other. Further
      characterization of mouse BACs encoding Obox1 and Obox2, as well as available BAC
      and EST sequences in GenBank, identified four closely related genes: Obox3,
      Obox4, Obox5, and Obox6. Northern blot analyses and RT-PCR from 10 different
      adult mouse tissues showed that the six Obox family transcripts are
      preferentially expressed in the gonads. In situ hybridization detected Obox1 and
      Obox6 transcripts exclusively in oocytes as early as one-layer follicles and
      throughout folliculogenesis. Obox1, Obox2, Obox3, Obox4, Obox5, and Obox6 map to
      proximal chromosome 7 in the mouse. The Obox1 and Obox2 genomic structures
      revealed the presence of six exons each. The Obox genes represent a new family of
      tissue-specific homeobox genes preferentially expressed in gonads.

PMID- 11991722
TI  - A sequence-based map of the nine genes of the human interleukin-1 cluster.
AB  - Six novel genes encoding proteins with the interleukin (IL)-1 fold have been
      identified recently. The classical family members are involved in inflammatory
      signaling. Previous work has placed the novel genes close to or within the same
      cluster as IL1A, IL1B, and IL1RN, which occupy an approximately 400-kb interval
      on chromosome 2. We have combined the incomplete public database sequence with
      our own sequence to generate a reference sequence and map that encompass all of
      the novel genes, allowing determination of the gene structures, precise
      localization of exons, and determination of distances between conventional SNP
      and microsatellite markers. Gene order from centromere to telomere is IL1A-IL1B
      IL1F7-IL1F9-IL1F6-IL1F8-IL1F5-IL1F10-IL1RN, of which only IL1A, IL1B, and IL1F8
      are transcribed towards the centromere. The gene order relates to the
      evolutionary relationship between the genes. Key features of exon boundaries are
      conserved. There is no evidence for other IL-1 family members within the cluster.

PMID- 11991723
TI  - Genomic organization of the interleukin-1 locus.
AB  - Recent additions have expanded the interleukin (IL)-1 gene family to 10 members.
      We have determined the order, orientation, and intergenic distance of the nine IL
      1 family genes that lie on human chromosome 2. We report cDNA sequences for the
      mouse orthologs of three of these genes. The order and orientation of the mouse
      genes have been mapped, and the mouse locus compared with the human locus. There
      is a break in the mouse locus of > 100 kb, compared with the human locus, located
      between Il1b and the most centromere-proximal of the novel mouse genes. The mouse
      seems to be missing an ortholog of human IL1F7.

PMID- 11991724
TI  - Genetic dissection of femur breaking strength in a large population (MRL/MpJ x
      SJL/J) of F2 Mice: single QTL effects, epistasis, and pleiotropy.
AB  - Bone breaking strength is an ultimate measurement of the risk of fracture. For a
      practical reason, bone mineral density (BMD) has been commonly used for
      predicting the risk instead. To identify genetic loci influencing femur-breaking
      strength (FBS), which was measured by three-point bending using an Instron
      DynaMight Low-Force Testing System, the whole-genome scan was carried out using
      119 polymorphic markers in 633 (MRLxSJL) F2 female mice. We identified six
      significant quantitative trait loci (QTL) affecting bone breaking strength on
      chromosomes 1, 2, 8, 9, 10, and 17, which together explained 23% of F2 variance.
      Of those, the QTL on chromosomes 2, 8, and 10 seem to be unique to bone breaking
      strength, whereas the remaining three QTL are concordant with femur BMD QTL.
      Genetic analysis suggests that, of these six FBS QTL, three influence BMD, two
      influence bone quality, and one influences bone size. We detected multiple
      significant epistatic interactions for FBS, which accounts for half (14.6%) of F2
      variance compared with significant single QTL effects. We found evidence that
      pleiotropic effect might represent a common genetic mechanism to coordinately
      regulate bone-related phenotypes. Pleiotropic analysis also suggests that our
      current threshold level for significant QTL may be too high to detect
      biologically significant QTL with small effect. Together with epistatic
      interactions, these undetected small QTL could explain 30% of genetic variance
      that remains unaccounted for in this study (heritability estimate for FBS is
      68%). Our findings in single QTL effects, epistasis, and pleiotropy demonstrate
      that partially overlapped but distinct combinations of genetic loci in MRL/MpJ
      and SJL/J inbred strains of mice regulate bone strength and bone density.
      Identification of the genes unique to FBS may have an impact on prediction of
      osteoporosis in human.

PMID- 11991725
TI  - Ancient duplications of the human proglucagon gene.
AB  - The human proglucagon gene (GCG) is encoded within a finished 576-kb DNA sequence
      generated by the Human Genome Project. GCG is flanked by 18 kb and 65 kb of DNA,
      5' and 3', respectively, that do not encode genes. The genomic sequence that
      includes GCG was found to have a long history of gene duplication events. Some
      members of the glucagon-like family of genes, GCG on chromosome 2 and GIP on
      chromosome 17, may be products of ancient genome duplications on the early
      vertebrate lineage. A large genomic tandem duplication event that included DPP4
      like and GCG genes occurred before the amphibian-mammal divergence, but one of
      the duplicated copies of GCG has been lost on the human lineage. Recently, a
      processed pseudogene of the X-chromosome-linked gene TIMM8A was inserted
      downstream of GCG. Some ancient duplicates of GCG may retain physiological
      functions in other vertebrates.

PMID- 11991726
TI  - Cardiac Na/Ca exchange function in rabbit, mouse and man: what's the difference?

PMID- 11991727
TI  - Troponin I Proteolysis and Myocardial Stunning: Now You See It-Now You Don>>t.

PMID- 11991728
TI  - Role of oxidative stress in myocardial hypertrophy and failure.

PMID- 11991729
TI  - Effects of Na(+)/Ca(2+)-exchanger overexpression on excitation-contraction
      coupling in adult rabbit ventricular myocytes.
AB  - The Na(+)/Ca(2+)-exchanger (NCX) is the main mechanism by which Ca(2+) is
      transported out of the ventricular myocyte. NCX levels are raised in failing
      human heart, and the consequences of this for excitation-contraction coupling are
      still debated. We have increased NCX levels in adult rabbit myocytes by
      adenovirally-mediated gene transfer and examined the effects on excitation
      contraction coupling after 24 and 48 h. Infected myocytes were identified through
      expression of green fluorescent protein (GFP), transfected under a separate
      promoter on the same viral construct. Control experiments were done with both non
      infected myocytes and those infected with adenovirus expressing GFP only.
      Contraction amplitude was markedly reduced in NCX-overexpressing myocytes at
      either time point, and neither increasing frequency nor raising extracellular
      Ca(2+) could reverse this depression. Resting membrane potential and action
      potential duration were largely unaffected by NCX overexpression, as was peak
      Ca(2+) entry via the L-type Ca(2+) channel. Systolic and diastolic Ca(2+) levels
      were significantly reduced, with peak systolic Ca(2+) in NCX-overexpressing
      myocytes lower than diastolic levels in control cells at 2 m m extracellular
      Ca(2+). Both cell relengthening and the decay of the Ca(2+) transient were
      significantly slowed. Sarcoplasmic reticulum (SR) Ca(2+) stores were completely
      depleted in a majority of myocytes, and remained so despite increasingly vigorous
      loading protocols. Depressed contractility following NCX overexpression is
      therefore related to decreased SR Ca(2+) stores and low diastolic Ca(2+) levels
      rather than reduced Ca(2+) entry.

PMID- 11991730
TI  - Effect of treatment on ventricular function and troponin I proteolysis in
      reperfused myocardium.
AB  - Effects of ischemia time and treatment interventions upon troponin I (TnI)
      proteolysis and function of reperfused myocardium were examined in isolated,
      perfused rabbit hearts. Hearts were randomized to 90 min aerobic perfusion, 15
      min low-flow (1 ml/min) ischemia (I) and 60 min reperfusion (R) or 60 min low
      flow I and 60 min R. Hearts subject to 60 min I and 60 min R received either no
      treatment, l -arginine treatment, or treatment with oxygen free radical (OFR)
      scavengers (mercapto-proponyl-glycine, catalase and superoxide dismutase). Hearts
      from cholesterol-fed rabbits were also studied after 60 min I and R. Isovolumic
      LV pressure and heart rate were recorded throughout and Western analysis of
      ventricular myocardium, using 3 specific antibodies, detected intact TnI (29 kDa)
      and TnI fragment (25 kDa). Hearts subject to 15 min I had minimal irreversible
      injury (TTC negative region=0.6+/-0.4% LV) but hearts subject to 60 min I had
      more extensive injury (TTC negative=40.7+/-5.8% LV). Recovery of rate-pressure
      product after 15 min I and 60 min R (56+/-9% of baseline) was better than after
      60 min I and 60 min R (23+/-9%, P<0.01). Both l -arginine and OFR scavengers were
      associated with better recovery of function after 60 min I, (66+/-7% and 72+/-3%
      of baseline respectively, P<0.01 v no treatment) but cholesterol hearts had poor
      recovery after 60 min I (37+/-8%). The 25 kDa TnI (% total TnI immunoreactivity)
      was 8.7+/-0.9% in controls, 10.0+/-1.6% after 15 min I and 60 min R, and 17.4+/
      2.4% after 60 min I and 60 min R (P<0.01 v controls and 15 min I). The proportion
      of 25 kDa TnI was increased in all hearts after 60 min I and did not change with
      treatment (l -arginine 16.8+/-1.8%, OFR scavengers 16.0+/-3.2%, cholesterol
      14.0+/-1.9%). There was no relation between proportion of 25 kDa TnI and recovery
      of function. Samples from freshly excised rabbit hearts and human right atria
      also had 25 kDa TnI (relative intensities 8.5+/-2.3% and 5.1+/-2.6%
      respectively). Although TnI fragmentation increases after prolonged ischemia and
      reperfusion, the functional recovery of stunned myocardium is independent of
      degree of TnI fragmentation.

PMID- 11991731
TI  - Cardiac expression and subcellular localization of the p38 mitogen-activated
      protein kinase member, stress-activated protein kinase-3 (SAPK3).
AB  - Despite the interest in the roles that mitogen-activated protein kinases (MAPKs)
      play in the heart, the role of the different MAPK isoforms has been relatively
      poorly defined. A third isoform of p38 MAPK, known variously as stress-activated
      protein kinase-3 (SAPK3), p38- gamma or ERK6, has been previously shown to differ
      from p38- alpha/ beta both in its molecular weight and its lack of inhibition by
      the compound SB203580. We have generated monoclonal antibodies with specificity
      for SAPK3 demonstrated by immunoblot analysis, immunofluorescence studies, and
      cloning of SAPK3 from a rat heart cDNA expression library. By immunoblotting, we
      confirmed high expression of SAPK3 in fast, slow and mixed fibre types of murine
      skeletal muscle and observed significant expression restricted to heart, lung,
      thymus and testes. In addition to expression in normal heart (human, mouse, rat,
      dog and pig), we observed constant expression in diseased human heart, as well as
      control and hypertrophic cultured neonatal rat cardiac myocytes.
      Immunolocalization in cultured cardiac myocytes followed by confocal microscopy
      showed punctate, non-nuclear SAPK3 staining. In contrast, p38- alpha/ beta
      staining was non-punctate and distributed throughout the cytosol and nucleus.
      Whereas treatment with Leptomycin B to prevent nuclear export processes promoted
      higher levels of p38- alpha/ beta staining in cardiac myocyte nuclei, there was
      no apparent change in SAPK3 localization under these conditions. These
      differences between p38- alpha/ beta and SAPK3 probably reflect the specialized
      functions of SAPK3 and emphasize the need to evaluate SAPK3 upstream activators
      and downstream targets in the heart.

PMID- 11991732
TI  - Effects of K(ATP) channel openers, P-1075, pinacidil, and diazoxide, on
      energetics and contractile function in isolated rat hearts.
AB  - We investigated the metabolic effects of a potent opener of ATP-sensitive K(+)
      (K(ATP)) channels, P-1075, in perfused rat hearts with the help of(31)P NMR
      spectroscopy. A 20 min infusion of 5 microm P-1075 depleted phosphocreatine and
      ATP by approximately 40%, concomitantly with a two-fold increase in inorganic
      phosphate, while oxygen consumption by the hearts increased by 50%. P-1075
      induced a cardiac contracture (left ventricular end diastolic pressure increased
      from 6 to 60 mmHg) and a cardiac arrest after an infusion of approximately 9 min.
      The effects were fully reversed by glibenclamide (5 microm), but not by sodium 5
      hydroxydecanoate (0.4 m m). A P-1075-related K(ATP) opener, pinacidil (0.3 m m),
      partially reversed the effects of P-1075, but a structurally unrelated opener,
      diazoxide (0.5 m m), had no effect. Pinacidil and diazoxide alone did not
      significantly affect PCr and ATP levels. Bioenergetic and functional effects
      similar to those of P-1075 were induced by infusion of a classic mitochondrial
      uncoupler, 2,4-dinitrophenol (50 microm); however, they were not abolished by
      glibenclamide. In addition, it was shown, using(87)Rb NMR, that both agents, P
      1075 and 2,4-dinitrophenol, resulted in a stimulation of Rb(+) efflux from the
      Rb(+) loaded rat hearts by approximately 130 and 65%, respectively, in a
      glibenclamide-sensitive manner. An inhibitory effect of P-1075 on ATP synthesis
      cannot be explained by its well-known action on sarcolemmal K(ATP) channels. We
      concluded that, unlike an uncoupling effect of 2,4-dinitrophenol, an inhibitory
      effect of P-1075 is produced by uncoupling of oxidative phosphorylation through
      the activation of mitochondrial K(ATP) channels.

PMID- 11991733
TI  - Distinct signaling pathways mediate cardiomyocyte phospholipase D stimulation by
      endothelin-1 and thrombin.
AB  - Several G protein-coupled receptors which stimulate phospholipase C (PLC) also
      activate phospholipase D (PLD) in cardiomyocytes. Here, we characterized PLD
      activation in neonatal rat cardiomyocytes by the PLC-stimulatory thrombin
      receptor PAR1, in comparison to the endothelin-1 receptor ET(A)R, which induces
      PLD stimulation by activation of protein kinase C (PKC) delta and epsilon.
      Similar to ET(A)R, activation of PAR1 induced PLD stimulation, which, however,
      was insensitive to PKC inhibition. Furthermore, in contrast to ET(A)R, PLD
      stimulation by PAR1 was suppressed by overexpression of regulators of G protein
      signaling specific for G(12)-type G proteins and treatment with brefeldin A, an
      inhibitor of guanine nucleotide exchange factors for ADP-ribosylation factor
      (ARF) GTPases. On the other hand, inactivation of Rho GTPases by Clostridium
      difficile toxin B and treatment with general tyrosine kinase inhibitors
      suppressed PAR1- and ET(A)R- as well as phorbol ester-induced PLD stimulation and
      was associated with a fall in the cellular level of phosphatidylinositol 4,5
      bisphosphate (PIP(2)). We conclude that, in contrast to ET(A)R-PLD coupling, PAR1
      induced cardiomyocyte PLD stimulation is PKC-independent and mediated by G(12)
      type G proteins and ARF GTPases, while Rho and tyrosine kinases regulate PLD
      stimulation by either receptor, apparently by controlling the cellular level of
      PIP(2), a common regulator of PLD activity.

PMID- 11991734
TI  - The role of SR Ca(2+)-content in blunted inotropic responsiveness of failing
      human myocardium.
AB  - The effects of inotropic agents are blunted in end-stage failing human
      myocardium. This has been related to a number of subcellular alterations
      including desensitization of the beta -adrenergic system. However, it is unknown
      whether alterations in SR Ca(2+)-handling contribute to blunted inotropic
      responsiveness of failing myocardium. We tested the hypothesis that the reduced
      effectiveness of Ca(2+)-dependent inotropic interventions results from the
      inability of the SR to sufficiently increase its Ca(2+)-content in failing human
      myocardium. Experiments were performed in ventricular muscle preparations from a
      total of four non-failing and 18 end-stage failing hearts. Isometric twitch force
      and SR Ca(2+)-content (using rapid cooling contractures; RCCs) were assessed
      under basal experimental conditions (1 Hz, 37 degrees C, [Ca(2+)](o) 2.5 mmol/l),
      and at increasing [Ca(2+)](o) (1.25-15 mmol/l), increasing concentrations of the
      beta -adrenergic agonist isoproterenol (ISO; 0.01-10 micromol/l), or the
      glycolytic substrate pyruvate (5-15 mmol/l). In addition, paired RCCs were evoked
      in a subset of experiments to investigate the relative contribution of SR Ca(2+)
      uptake v Na(+)/Ca(2+)-exchange to cytosolic Ca(2+)-elimination. In non-failing
      human myocardium, Ca(2+), ISO, and pyruvate exerted significant positive
      inotropic effects (increase in twitch force by maximally 396%, 437%, and 82%,
      respectively). The inotropic effects were associated with increasing RCCs (by
      147%, 193%, and 51%, respectively). In failing myocardium, the inotropic effects
      of Ca(2+) and ISO were significantly less pronounced (with maximal increases in
      twitch force by 226% and 138%, respectively), associated with blunted effects on
      RCCs (increase by 33% and 79%, respectively). In contrast, the inotropic effect
      of pyruvate was unchanged in failing myocardium (increase by 66%), while the
      corresponding RCCs increased only by 30%. We conclude that the inotropic effects
      of Ca(2+), ISO, and pyruvate are associated with a significant increase in SR
      Ca(2+)-content in non-failing human myocardium. In end-stage failing myocardium,
      the reduced inotropic response to Ca(2+) and ISO is associated with the inability
      of the SR to appropriately increase its Ca(2+)-content, possibly related to
      decreased SR Ca(2+)-ATPase and increased Na(+)/Ca(2+)-exchanger expression. In
      contrast, the maintained inotropic response to pyruvate despite reduced SR Ca(2+)
      loading points to additional subcellular effects such as enhanced myofilament
      Ca(2+)-responsiveness.

PMID- 11991735
TI  - In vitro motility analysis of thin filaments from failing and non-failing human
      heart: troponin from failing human hearts induces slower filament sliding and
      higher Ca(2+) sensitivity.
AB  - Contractility of the myocardium is altered in end-stage heart failure. We
      investigated whether this was related to functional changes in troponin. We
      isolated troponin from 1 g samples of end-stage failing, non-failing and foetal
      human heart and studied its regulation of actin-tropomyosin movement over
      immobilised HMM by in vitro motility assay. At pCa5.4 the sliding velocity of
      thin filaments reconstituted with non-failing heart troponin was 52+/-4% more
      than actin-tropomyosin, with failing heart troponin velocity increased by 35+/-2%
      and with foetal heart troponin velocity increased by 11+/-4%. Thin filaments
      containing troponin from failing hearts were more Ca(2+)-sensitive than non
      failing heart troponin. EC(50) for the fraction of filaments motile and filament
      velocity decreased 1.76+/-0.20 and 1.89+/-0.62-fold respectively relative to non
      failing heart troponin. With foetal heart troponin the EC(50) decreased 2.16+/
      0.23 and 3.50+/-1.73-fold for fraction and velocity respectively. Western blots
      revealed no difference in troponin T or troponin I isoform expression in troponin
      from failing and non-failing adult hearts but foetal isoforms of troponin I and T
      were observed in troponin from foetal heart. The level of PKA phosphorylation of
      troponin from failing and non-failing heart was not significantly different,
      however, complete non-specific dephosphorylation of troponin abolished most of
      the difference between failing and non-failing heart troponin. These findings
      show functional alterations in troponin in failing hearts which could account for
      the reduced contractile function but there is no change in troponin isoform
      expression or PKA phosphorylation. Differential phosphorylation by other kinases
      may account for altered troponin function.

PMID- 11991737
TI  - Politics and AIDS: a bad mix.

PMID- 11991736
TI  - Activation of protein kinase B/Akt by urocortin is essential for its ability to
      protect cardiac cells against hypoxia/reoxygenation-induced cell death.
AB  - Urocortin (Ucn), is a peptide related to hypothalamic corticotrophin-releasing
      factor (CRF) and binds with a high affinity to the CRF-R2 beta receptor which is
      expressed in the heart. Ucn promotes cardiac myocyte survival against hypoxia
      reoxygenation (HR) injury and this involves activation of the mitogen activated
      protein kinase pathway (MEK1/2 p42/44 MAPK). In this study we report that Ucn
      stimulates the phosphorylation of protein kinase B (PKB/Akt) via
      phosphatidylinositol (PI) 3-OH kinase (PI-3 kinase). To investigate the
      signalling pathways that mediate the anti-apoptotic and cell survival effect of
      Ucn in hypoxia reoxygenation (HR), gene based inhibitors of MEK1/2, PI-3 kinase
      and Akt were over-expressed in rat neonatal cardiac myocytes and cell survival
      effects against HR were assessed. The dominant negative mutants of the MEK1/2, PI
      3 kinase and Akt inhibited Ucn mediated cardioprotection in HR and active PI-3
      kinase was itself cardioprotective. In addition, chemical inhibitors of the PI-3
      kinase pathway, wortmannin and LY294002 inhibit Ucn mediated cardioprotection in
      HR in both neonatal and adult cardiac myocytes. Hence the PI-3 kinase/Akt pathway
      is required in addition to MEK1/2 to mediate Ucn cardioprotection in HR. To our
      knowledge this is the first report of the activation of the PI-3 kinase/Akt
      pathway by a member of the CRF family of peptides.

PMID- 11991738
TI  - Cabo II: immunology and gene therapy.

PMID- 11991739
TI  - Molecular therapies for colorectal cancer metastatic to the liver.
AB  - Colorectal cancers are the fourth most commonly diagnosed cancers and will
      account for over 56,000 deaths in the United States in 2002. A majority of
      patients with advanced colorectal cancer develop liver metastases during the
      course of their disease. Treatment of colorectal cancer metastatic to the liver
      by surgery or chemotherapy is limited and most patients succumb to their disease.
      Therefore, a broad spectrum of novel treatments, including innovative molecular
      therapies such as gene and immunotherapy or replication-competent viral therapy,
      is under preclinical investigation and several clinical trials are in progress.
      Here we review molecular therapies for colorectal cancer metastatic to the liver.

PMID- 11991740
TI  - Fetal gene transfer by intrauterine injection with microbubble-enhanced
      ultrasound.
AB  - Intrauterine injection of naked DNA expressing luciferase, green fluorescent
      protein (GFP), or beta-galactosidase (beta-gal) and fluorescein isothiocyanate
      labeled oligodeoxynucleotide (FITC-ODN), in combination with microbubble-enhanced
      ultrasound (US), referred to as the "shotgun method" (SGM), produced high-level
      protein expression in fetal mice. With the SGM, luciferase expression increased
      approximately 10(3)-fold in comparison with expression after injection of naked
      DNA alone. Electron microscopic analysis demonstrated transient formation of
      pores on the skin surface after intraamniotic (i.a.) injection with the SGM.
      Widespread expression of GFP and beta-gal and delivery of FITC-ODN were observed
      in multiple fetal tissues adjacent to the injection points. PCR analysis
      indicated that germline transfection was only transient following intraperitoneal
      (i.p) injection, and there was no evidence of transfer of the reporter gene to
      the offspring. Thus, SGM might provide a useful means to clarify the molecular
      mechanisms of genetic diseases in utero, as well as a tool to develop gene
      therapies in utero.

PMID- 11991741
TI  - Adenoviral-mediated, high-level, cell-specific transgene expression: a SYN1-WPRE
      cassette mediates increased transgene expression with no loss of neuron
      specificity.
AB  - Viral vectors are excellent tools for studying gene function in the brain,
      although a limitation has been the ability to effectively target transgene
      expression to specific neuronal populations. This generally cannot be overcome by
      the use of neuron-specific promoters, as most are too large to be used with
      current viral vectors and expression from these promoters is often relatively
      weak. We therefore developed a composite expression cassette, comprising 495 bp
      of the weak human SYN1 (synapsin-1) promoter and 800 bp of the woodchuck
      hepatitis virus posttranscriptional regulatory element (WPRE). Studies in
      hippocampal cultures, organotypic cultures, and in vivo showed that the 3'
      addition of the WPRE to the SYN1 element greatly increased enhanced green
      fluorescent protein expression levels with no loss of neuronal specificity. In
      vivo studies also showed that transgene expression was enhanced with no loss of
      neuronal specificity in dentate-gyrus neurons for at least 6 weeks following
      transfection. Therefore, unlike most powerful promoter systems, which mediate
      expression in neurons and glia, this SYN1-WPRE cassette can target powerful long
      term transgene expression to central nervous system neurons when delivered at
      relatively low titers of adenovirus. Its use should therefore facilitate both
      gene therapy studies and investigations of neuronal gene function.

PMID- 11991742
TI  - Delivery of FGF genes to wound repair cells enhances arteriogenesis and
      myogenesis in skeletal muscle.
AB  - Tissue repair is driven by migratory macrophages and fibroblasts that infiltrate
      injury sites and secrete growth factors. We now report the enhancement of
      skeletal muscle repair by targeting transgene delivery to these repair cells
      using matrix-immobilized gene vectors. Plasmid and adenovirus vectors immobilized
      in collagen-gelatin admixtures were delivered to excisional muscle wounds, and
      when encoding either fibroblast growth factor-2 (FGF2) or FGF6 transgenes,
      produced early angiogenic responses that subsequently remodeled into
      arteriogenesis. FGF2 gene delivery enhanced the number of CD31(+) endothelial
      cells present at treatment sites > 6-fold by day 14, and muscular arteriole
      density up to 11-fold by day 21 (P<0.0001). Muscle repair was also enhanced, as
      FGF gene-treated wounds filled with regenerating myotubes expressing the marker
      CD56 (an average 20-fold increase in CD56 expression versus controls, P<0.0001).
      These responses required transfection of a threshold level of repair cells,
      achievable only in injured muscles, and were transgene-driven, as neither
      platelet-derived growth factor-B (PDGFB) gene nor FGF2 protein delivery produced
      equivalent responses. In conclusion, using biomatrices to direct gene delivery to
      repair cells allows for relatively complex regenerative processes such as
      arteriogenesis and myogenesis, and therefore represents a promising approach to
      treating injured and ischemic muscle.

PMID- 11991743
TI  - Targeted transduction patterns in the mouse brain by lentivirus vectors
      pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV envelope proteins.
AB  - Lentiviral vectors have proven to be promising tools for transduction of central
      nervous system (CNS) cells in vivo and in vitro. In this study, CNS transduction
      patterns of lentiviral vectors pseudotyped with envelope glycoproteins from Ebola
      virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV),
      or the rabies-related Mokola virus were compared to a vector pseudotyped with the
      vesicular stomatitis virus glycoprotein (VSV-G). Mokola-, LCMV-, and VSV-G
      pseudotyped vectors transduced similar populations, including striatum, thalamus,
      and white matter. Mokola-pseudotyped vectors were the most efficient of the
      three. MuLV-pseudotyped lentivirus efficiently transduced striatum and
      hippocampal dentate gyrus. In contrast, no transduction resulted from injection
      of Ebola-pseudotyped virus in the CNS. The same pattern was observed in vitro
      with primary cultured oligodendrocytes. LCMV, MuLV, and Ebola pseudotypes were
      the most stable. These results demonstrate that targeted transduction in the CNS
      can be achieved using specific envelope glycoproteins to pseudotype lentiviral
      vectors, and support the use of Mokola-pseudotyped and MuLV-pseudotyped
      lentiviral vectors as efficient and stable alternatives to VSV-G-pseudotyped
      vectors for experiments in the mouse CNS.

PMID- 11991744
TI  - Cell surface heparan sulfate is a receptor for attachment of envelope protein
      free retrovirus-like particles and VSV-G pseudotyped MLV-derived retrovirus
      vectors to target cells.
AB  - Non-infectious, envelope protein-free, retrovirus-like particles (VLP) derived
      from either Moloney murine leukemia virus (MLV) or human HIV are able to bind
      efficiently to, but not infect, target cells. Upon subsequent addition to the
      bound particles of the G protein of vesicular stomatitis virus (VSV-G), an
      efficient surrogate retrovirus envelope protein, the VLP are efficiently taken up
      by the cells to produce infection. Cell attachment of the VLP is efficiently
      inhibited by soluble heparin and dextran sulfate and less efficiently abrogated
      by several other glycosaminoglycans (GAGs) including chondroitin sulfate A and
      chondroitin sulfate B (dermatan sulfate), as determined by deconvolution
      microscopic immunodetection of the viral gag protein and by quantitative binding
      studies of metabolically labeled (35)S-VLP. Enzymatic digestion of heparan
      sulfate (HS) from the cell surface with heparinase I also reduces VLP binding.
      Furthermore, VLP adsorption onto several CHO cell lines variably deficient in
      cell surface GAG is significantly but incompletely abrogated. De-sulfated
      heparins are less efficient than native heparin in inhibiting the Polybrene
      mediated binding of VLP, whereas growth of human cells in the presence of sodium
      chlorate leads to significant reduction of Polybrene-mediated VLP binding. In
      addition, specific inhibition of VLP binding and infectivity of mature infectious
      VSV-G-pseudotyped virus is observed in the presence of heparin and HS under
      Polybrene-free conditions. We conclude from these studies that the presence of
      Polybrene, the degree of sulfation of cell surface GAG, and possibly the presence
      of charged cell surface macromolecules create an electrostatic environment that
      promotes optimum binding of VLP to cells. Additionally, our results demonstrate
      that, in the absence of Polybrene, initial attachments of non-infectious,
      envelope protein-free VLP and probably mature infectious virus particles are
      mediated by interactions of the virus particles with cell surface heparan
      sulfate, and possibly with other GAG molecules.

PMID- 11991745
TI  - Endostatin gene transfer inhibits joint angiogenesis and pannus formation in
      inflammatory arthritis.
AB  - Rheumatoid arthritis is a prevalent example of an inflammatory angiogenic
      disease, which is mediated by pro-inflammatory and pro-angiogenic cytokines such
      as tumor necrosis factor (TNF). To evaluate the effect of the potent anti
      angiogenic factor endostatin on TNF-induced inflammatory arthritis, we injected
      an endostatin-expressing lentiviral vector directly into the joints of human TNF
      transgenic mice before the onset of disease. Histological analysis of the
      injected joints 8 weeks later revealed that endostatin reduced blood vessel
      density within the synovial tissues and an overall mean arthritis index. In vitro
      and in vivo examination of the potential mechanism by which endostatin inhibited
      the arthritis revealed that endostatin blocks TNF-induced activation of JNK and
      JNK-dependent pro-angiogenic gene expression. These data suggest a novel
      mechanism by which endostatin inhibits angiogenesis, and demonstrates the
      potential utility of anti-angiogenic gene therapy for treatment of inflammatory
      arthritis.

PMID- 11991746
TI  - Lentiviral vectors for sustained transgene expression in human bone marrow
      derived stromal cells.
AB  - Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as
      potential platforms for the systemic delivery of therapeutic proteins in vivo
      following gene transfer using oncogenic retroviruses. However, the major
      limitations of this strategy include low levels of gene transfer and a general
      lack of long-term transgene expression. We have investigated the expression of
      several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene
      transfer. Vectors containing a variety of strong promoters driving enhanced green
      fluorescence protein (EGFP) and coral (Discosoma sp.)-derived red fluorescent
      protein (DsRed) reporter genes pseudotyped with the vesicular stomatitis virus-G
      (VSV-G) glycoprotein were able to transduce cultured MSCs with high efficiency.
      Transduction efficiencies and transgene expression levels in MSCs were found to
      be higher with lentiviral vectors than with a vector based on the murine stem
      cell virus pseudotyped with VSV-G. Transgene expression was maintained in culture
      for at least 5 months. HIV-1-based lentiviral vectors were able to transduce
      clonogenic mesenchymal progenitor cells, which were capable of maintaining
      transgene expression by their MSC progeny, over several cell divisions and during
      differentiation into adipocytes, indicating that terminal adipocyte cell
      differentiation was unaffected by lentivirus-mediated reporter gene transfer.
      Collectively these results suggest that lentivirus-mediated gene transfer
      strategies provide an efficient tool for ex vivo modification of MSCs that does
      not interfere with differentiation.

PMID- 11991747
TI  - New methods to titrate EIAV-based lentiviral vectors.
AB  - Ideally, gene transfer vectors used in clinical protocols should only express the
      gene of interest. So far most vectors have contained marker genes to aid their
      titration. We have used quantitative real-time PCR to titrate equine infectious
      anemia virus (EIAV) vectors for gene therapy applications. Viral RNA was isolated
      from vector preparations and analyzed in a one-step RT-PCR reaction in which
      reverse transcription and amplification were combined in one tube. The PCR assay
      of vector stocks was quantitative and linear over four orders of magnitude. In
      tandem, the integration efficiency of these vectors has also been determined by
      real-time PCR, measuring the number of vector genomes in the target cells. We
      have found that these methods permit reliable and sensitive titration of
      lentiviral vectors independent from the expression of a transgene. They also
      allow us to determine the integration efficiency of different vector genomes.
      This technology has proved very useful, especially in the absence of marker genes
      and where vectors express multiple genes.

PMID- 11991748
TI  - Correction of the enzymatic and functional deficits in a model of Pompe disease
      using adeno-associated virus vectors.
AB  - Pompe disease is a lysosomal storage disease caused by the absence of acid alpha
      1,4 glucosidase (GAA). The pathophysiology of Pompe disease includes generalized
      myopathy of both cardiac and skeletal muscle. We sought to use recombinant adeno
      associated virus (rAAV) vectors to deliver functional GAA genes in vitro and in
      vivo. Myotubes and fibroblasts from Pompe patients were transduced in vitro with
      rAAV2-GAA. At 14 days postinfection, GAA activities were at least fourfold higher
      than in their respective untransduced controls, with a 10-fold increase observed
      in GAA-deficient myotubes. BALB/c and Gaa(-/-) mice were also treated with rAAV
      vectors. Persistent expression of vector-derived human GAA was observed in BALB/c
      mice up to 6 months after treatment. In Gaa(-/-) mice, intramuscular and
      intramyocardial delivery of rAAV2-Gaa (carrying the mouse Gaa cDNA) resulted in
      near-normal enzyme activities. Skeletal muscle contractility was partially
      restored in the soleus muscles of treated Gaa(-/-) mice, indicating the potential
      for vector-mediated restoration of both enzymatic activity and muscle function.
      Furthermore, intramuscular treatment with a recombinant AAV serotype 1 vector
      (rAAV1-Gaa) led to nearly eight times normal enzymatic activity in Gaa(-/-) mice,
      with concomitant glycogen clearance as assessed in vitro and by proton magnetic
      resonance spectroscopy.

PMID- 11991749
TI  - The effect of cell division on the cellular dynamics of microinjected DNA and
      dextran.
AB  - Gene delivery is a multistep process that is being studied to increase its
      efficiency, a major hurdle for effective gene therapy. Our study focused on the
      nuclear entry step by microinjecting a mixture of fluorescent dextran and the
      pEYFP-Nuc plasmid (encoding a nuclear-targeted, enhanced GFP) into the cytoplasm
      of nondividing and dividing cells that were selected using non-chemical means.
      After 10 and 1000 ng/microl of plasmid DNA (pDNA) were cytoplasmically injected,
      28% and 50% of the cells that had not divided expressed GFP, respectively,
      compared with 50% and 90% for the cells that had divided. This result suggested
      that pDNA can enter the nonmitotic nuclei of mononucleated cells, albeit at a
      lower efficiency than mitotic nuclei. The ability of pDNA to enter the intact
      nuclei of nondividing cells is consistent with our previous experience using
      multinucleated myotubes and digitonin-permeabilized cells in culture and using
      intravascular naked pDNA delivery in vivo. An explanation for the small effect of
      cell division was provided by studies using fluorescently labeled molecules and
      confocal fluorescent microscopy. They showed that the bulk of large dextran, and
      similarly pDNA, was excluded from re-formed nuclei after mitosis, thereby
      limiting the effect of cell division on the nuclear entry of pDNA.

PMID- 11991750
TI  - Topological constraints governing the use of the chicken HS4 chromatin insulator
      in oncoretrovirus vectors.
AB  - The expression of integrated oncoretrovirus vectors is subject to the inhibitory
      effects of surrounding chromatin. A previous report from our laboratory indicated
      that such position effects can be overcome by flanking a reporter vector with the
      cHS4 chromatin insulator. To characterize this activity more thoroughly, we
      switched the promoter-gene combinations in the reporter vector and analyzed
      expression of these vectors flanked with the cHS4 fragment in both orientations
      following bone marrow transduction and transplantation in mice. The results
      indicate that the cHS4 fragment can function in both orientations and can
      insulate both the virus long-terminal-repeat (LTR) promoter and an internal
      phosphoglycerate kinase (Pgk) promoter. However, insulation of the LTR promoter
      diminished when the orientation of the cHS4 fragment placed the CTCF-binding core
      element immediately proximal to the U3 region, suggesting a minimal distance
      requirement. Moreover, placement of the cHS4 fragment in the U3 region of the 3'
      LTR dramatically decreased the level of expression from an internal Pgk promoter,
      presumably by blocking interaction with the 3' LTR enhancer. Finally, sorting
      studies suggest that the severity of position effects or autonomous promoter
      silencing increases as transduced progenitors differentiate into mature progeny.
      These findings have direct implications for the use of chromatin insulators such
      as cHS4 in oncoretrovirus vectors.

PMID- 11991751
TI  - A novel, helper-dependent, adenovirus-retrovirus hybrid vector: stable
      transduction by a two-stage mechanism.
AB  - We have developed a novel vector system that uses a helper-dependent adenoviral
      vector as a carrier to deliver a fully functional retrovirus vector. The helper
      dependent adenovirus (HDAd) can accommodate large inserts, provide high titers,
      and infect nondividing as well as dividing cells. However, adenoviral DNA is
      rarely integrated into the host cell genome, and its episomal expression is
      transient. Therefore we inserted a replication-competent, ecotropic retrovirus
      vector containing the green fluorescent protein (GFP) reporter gene as a second
      stage component. The well-characterized host species tropism of each vector
      component provided a stringent biological assay system that demonstrates the two
      stage transduction mechanism of the hybrid vector, because the adenovirus stage
      can efficiently transduce human cells but cannot replicate in murine cells, and
      conversely, the ecotropic retrovirus stage cannot enter human cells but can
      efficiently proliferate in murine cells, resulting in permanent integration and
      progressive spread of reporter gene expression.

PMID- 11991752
TI  - Significant antitumor effects obtained by autologous tumor cell vaccine
      engineered to secrete interleukin (IL)-12 and IL-18 by means of the EBV/lipoplex.
AB  - The EBV/lipoplex is a nonviral gene delivery system composed of a cationic lipid
      and Epstein-Barr virus (EBV)-based plasmid vector that carries the EBV oriP and
      EBV nuclear antigen 1 (EBNA1) gene. Because the EBNA1 supports retention, nuclear
      localization, and transcriptional upregulation of the oriP-bearing plasmid, cells
      transfected with the EBV/lipoplex express the transgene at a very high level. We
      hypothesized that tumor cells genetically manipulated with the EBV/lipoplex may
      be used as a tumor vaccine without drug selection, strongly contributing to
      immunotherapy of patients with malignancies. The cytokines interleukin (IL)-12
      and IL-18 exert a variety of immune-regulatory functions including interferon
      (IFN)-gamma production and cytotoxic T lymphocyte (CTL) and natural killer (NK)
      activation. Here, we investigated the possible therapeutic effects of an
      autologous tumor cell vaccine in the B16 melanoma model. The vaccine was
      engineered to secrete IL-12 and IL-18 by means of the EBV/lipoplex. B16 cells
      were subcutaneously implanted into syngenic mice followed by repetitive
      immunization with irradiated B16 cells that had been transfected 3 days earlier
      by TFL2-3, a novel cationic lipid, with EBV-plasmid vectors encoding IL-12 and/or
      IL-18 genes (B16/mIL-12, B16/mIL-18, and B16/mIL-12+mIL-18). The mice vaccinated
      with B16/mIL-12 underwent strong tumor suppression accompanied by a high IFN
      gamma production. Both CTL and NK activities were significantly elevated in these
      mice. When the tumor cell vaccine was prepared by means of conventional (non-EBV)
      plasmid vectors combined with the same cationic lipid, the therapeutic outcome
      was not as good, suggesting the superiority of the EBV-based plasmid in
      engineering these types of tumor vaccines. Vaccination with B16/mIL-18 was not
      effective in suppressing tumors, whereas B16/mIL-12+mIL-18 showed comparable
      antitumor therapeutic validity as B16/mIL-12 did. When IFN-gamma mutant (IFN
      gamma(-/-) mice were treated, B16/mIL-12 vaccine did not show any therapeutic
      activity, suggesting the necessity of IFN-gamma in the anti-melanoma immune
      responses. In contrast, the antitumor effect was not affected by NK depletion in
      mice that received repetitive injections with anti-asialo GM1 antibody.
      Furthermore, vaccination with B16/mIL-12 significantly suppressed pulmonary
      metastases in mice that had been intravenously injected with parental B16. Our
      results suggest that the EBV/lipoplex is quite useful in generating an autologous
      tumor cell vaccine and that IL-12 is an important component of the vaccine.

PMID- 11991753
TI  - Enhanced secretion and uptake of beta-glucuronidase improves adeno-associated
      viral-mediated gene therapy of mucopolysaccharidosis type VII mice.
AB  - Previous treatment of mucopolysaccharidosis type VII mice (Sly syndrome) with AAV
      vectors has resulted in increased levels of beta-glucuronidase (GUS) enzyme in
      some tissues with reduction of glycosaminoglycan storage granules and improved
      health. By adding coding sequences for secretion (Igkappa) and uptake (HIV-1 TAT)
      signals to the GUS gene delivered by AAV, and treating mice both intrathecally
      and intravenously as newborns, we have increased the GUS enzyme levels in more
      tissues and have improved the health of the mice so much that they are able to
      breed. The levels of GUS in the serum were above normal in some mice, which
      caused reduction of storage in the spleen, a nontransduced tissue. The heart and
      aorta showed therapeutic levels of GUS enzyme. AAV GUS DNA was found in brain and
      liver, which showed no storage. Phenotypically the treated mice were more active
      and showed less stunted skeletal growth. The pups born to these mice were not
      affected by the gene therapy, as shown by mutant levels of GUS enzyme in their
      tissues and the absence of AAV GUS DNA. However, they were resistant to
      intravenous treatment with AAV GUS due to the mother's antibodies, but not to
      intrathecal treatment.

PMID- 11991754
TI  - E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable
      of highly specific replication in AFP-producing hepatocellular carcinoma and
      eradication of established tumor.
AB  - Here, we constructed a recombinant replication-competent adenovirus (rRCAd;
      AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP)
      enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the
      AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We
      then examined the feasibility of gene therapy utilizing this virus for AFP
      producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing
      HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of
      infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at
      a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC
      cells with a higher specificity and potency than previously reported.
      Furthermore, this virus was capable of complete eradication of a preestablished
      HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units
      (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

PMID- 11991755
TI  - Characterization of retroviral gene transfer into highly purified human CD34(-)
      cells with primitive hematopoietic capacity.
AB  - Primitive human hematopoietic cells have recently been identified within a rare
      subfraction of CD34(-) lineage-depleted (Lin(-)) cells and further characterized
      by their restriction to a rarer subset expressing AC133. Here we show that CD34(
      )AC133(+)Lin(-) cells can be transduced by retrovirus at a comparatively higher
      efficiency than either CD34(-)AC133(-)Lin(-) or CD34(+)CD38(-)Lin(-) cells.
      Subpopulations were transduced by enhanced green fluorescent protein (eGFP)
      containing retrovirus in serum-free conditions. During the culture period, both
      CD34(-)AC133(+)Lin(-) and CD34(+)CD38(-)Lin(-) subfractions expanded, whereas
      CD34(-)AC133(-)Lin(-) cells could not be sustained. Fluorescent microscopic
      examination of progenitors assayed by colony-forming units (CFU) derived from
      CD34(-)AC133(+)Lin(-) cells revealed expression of eGFP, with the presence of
      provirus confirmed by clonal PCR analysis. Flow cytometry detecting eGFP revealed
      that cultures seeded with CD34(-)AC133(+)Lin(-) cells had a greater than
      threefold higher frequency of eGFP(+) cells compared with transduced cultures of
      CD34(+)CD38(-)Lin(-) cells. Our results demonstrate that retroviral transduction
      efficiency and level of transgene expression into CD34(-)AC133(+)Lin(-) cells is
      distinct to either CD34(-)AC133(-)Lin(-) or CD34(+)CD38(-)Lin(-) cells. This
      study represents the first evaluation of retroviral transduction into this
      population of primitive CD34(-) cells, and therefore provides the basis for
      optimization of gene transfer protocols to examine the role of gene-marked CD34(
      ) stem cells in a clinical setting.

PMID- 11991756
TI  - Rep/Cap gene amplification and high-yield production of AAV in an A549 cell line
      expressing Rep/Cap.
AB  - Cell lines stably expressing rep/cap are important tools for studying adeno
      associated virus (AAV) biology and producing AAV vectors. Several rep/cap cell
      lines have been isolated, each of which is based on HeLa cells. Infection of
      these cell lines with adenovirus for production of AAV vector is associated with
      substantial amplification of the rep/cap gene. Concerns over the presence of
      human papilloma viral (HPV) sequences in HeLa cells may limit use of such lines
      for production of clinical-grade vectors. Here we describe a non-HeLa-derived
      rep/cap cell line called K209, generated by stable transfection of A549 cells
      with a plasmid construct containing the P5 rep/cap cassette from AAV2. Infection
      of K209 cells with adenovirus leads to a 1000-fold amplification of the rep/cap
      gene with high-yield production of AAV vectors. The multiplicity of infection
      (MOI) of adenovirus that led to maximum amplification of the rep/cap gene and
      high-level production of AAV is 10 times higher in the HeLa-based cell line than
      that required in K209 cells. Our data suggest that papilloma-derived gene
      products present in HeLa cells are not required for high-yield production of AAV
      vectors.

PMID- 11991758
TI  - Open field habituation learning is improved by nicotine and attenuated by
      mecamylamine administered posttrial into the nucleus accumbens.
AB  - Using the paradigm of habituation learning in the open field, we tested the
      effects of unilateral microinjections of the agonist nicotine (8.0, 40.0, and
      80.0 microg) and the nicotine receptor antagonist mecamylamine (0.1, 1.0, 10.0
      microg) into the core of the nucleus accumbens. When injected posttrial, that is,
      immediately after the first exposure to the open field, nicotine dose-dependently
      enhanced behavioral habituation during the test on the following day, indicating
      a facilitation of memory, whereas mecamylamine impaired habituation at the
      highest dose, but not at the two lower doses. When injected 5 h after the
      learning trial, nicotine (40 microg) and mecamylamine (10 microg) impaired
      habituation on the subsequent day. A control experiment did not provide evidence
      for possible proactive effects of mecamylamine. These findings are discussed with
      respect to the possible behavioral functions of cholinergic, and especially
      nicotinic, mechanisms in the nucleus accumbens. They may also be relevant for
      understanding cholinergic-linked psychopathologies such as Alzheimer's disease,
      since the nucleus accumbens is one of the sites where cholinergic neurons are
      lost in this neurodegenerative disease.

PMID- 11991759
TI  - The role of PKA, CaMKII, and PKC in avoidance conditioning: permissive or
      instructive?
AB  - This article explores the causal and correlative relationships between kinases
      and learning and memory. Specifically, the contributions of three kinases-protein
      kinase A (PKA), calcium calmodulin-dependent kinase II (CaMKII), and protein
      kinase C (PKC)-are assessed during the consolidation phase of avoidance
      conditioning. The following sources of evidence are considered: inhibitor data,
      activity monitoring, and transgenic studies. An exhaustive effort is made to
      address several issues regarding the participation of these kinases in (a)
      posttraining timing and magnitude, (b) location across many brain regions, and
      (c) the use of multiple pharmacological agents and assays. In addition, this
      article attempts to integrate the behavioral data with the purported role of
      kinases in long-term potentiation (LTP).

PMID- 11991760
TI  - Inhibition of guanylate cyclase and protein kinase G impairs retention for the
      passive avoidance task in the day-old chick.
AB  - Nitric oxide (NO) is a highly labile chemical messenger which has previously been
      implicated in memory processes in a variety of learning paradigms and species.
      However, there is only limited evidence to suggest which enzymes are acted upon
      by NO during the formation of memory. The present study investigates the role of
      guanylate cyclase (GC) and protein kinase G (PKG) in a form of passive avoidance
      learning known to be dependent on nitric oxide activity. It was determined that
      in vivo pharmacological inhibition of GC using either 1H-[1,2,4]oxadiazolo[4,3,
      a]quinoxalin-1-one or 6-anilino-5,8-quinolinedione resulted in two transitory
      memory retention deficits centred around 40 and 120 min posttraining,
      respectively. In contrast, inhibition of PKG with N-[2-(methylamino)ehtyl]-5
      isoquinoline-sulfornamide hydrochloride (H-8) resulted in a single temporary
      retention loss centered at 120 min posttraining. These temporary retention losses
      appear to be specific to memory since they were dose-dependent and could not be
      explained by nonspecific performance effects. Further, these results suggest that
      these agents inhibit memory retrieval rather than formation, since memory is
      subsequently available. The current findings indicate that guanylyl cyclase
      mediates two memory retrieval processes, the latter of which appears to be PKG
      dependent. In contrast, since inhibition of NO results in a permanent retention
      loss, it is suggested that NO is required for memory formation through GC
      independent processes.

PMID- 11991761
TI  - Effects of MK-801 and ethanol combinations on memory consolidation in CD1 mice:
      involvement of GABAergic mechanisms.
AB  - In the present research the effect of the noncompetitive N-methyl-d-aspartate
      receptor antagonist MK-801 and ethanol combinations on memory consolidation and
      the involvement of GABAergic mechanisms in this effect were investigated in CD1
      mice injected intraperitoneally with the drugs immediately or 120 min after
      training in a one-trial inhibitory avoidance apparatus and tested for retention
      24 h later. The results showed that (a) the retention performances of mice were
      impaired in a dose-dependent manner by immediate posttraining MK-801 (0.2 and
      0.3, but not 0.1 mg/kg) and ethanol (1 and 2, but not 0.5 g/kg) administrations;
      (b) an otherwise ineffective dose of MK-801 (0.1 mg/kg) enhanced the deleterious
      effect exerted by ethanol (1 and 2 g/kg); (c) an otherwise ineffective dose of
      muscimol (0.5 mg/kg) enhanced, while otherwise ineffective doses of picrotoxin
      (0.25 mg/kg) or bicuculline (0.1 mg/kg) antagonized, this effect; and (d) no
      effect was observed when the treatments were carried out 120 min after training,
      suggesting that the effects observed following immediate posttraining
      administrations were due to the influence on the consolidation of memory. From
      these experiments it is evident that (a) MK-801 enhances ethanol's effects on
      memory consolidation and (b) GABAergic mechanisms are involved in this effect.

PMID- 11991762
TI  - The amygdala but not the hippocampus is involved in pattern separation based on
      reward value.
AB  - A total of 32 male Long-Evans rats were tested on a modified version of Flaherty,
      Turovsky, and Krauss's (1994) anticipatory contrast paradigm to assess pattern
      separation for reward value. Prior to testing, each rat received either a
      control, a hippocampal, or an amygdala lesion. In the home cage, each rat was
      allowed to drink a water solution containing 2% sucrose for 3 min followed by a
      water solution containing 32% sucrose for 3 min. Across 10 days of testing, the
      rats in each lesion group showed significantly increased anticipatory
      discriminability as a function of days. To assess the operation of a pattern
      separation mechanism, each rat was then tested using the same procedure except
      the 2% solution was followed by a 16% solution for 10 days and then by an 8%
      solution for 10 days. Control and hippocampal-lesioned rats continued to show
      high discriminability when the 2% solution was followed by a 16% solution;
      however, the amygdala-lesioned rats showed low anticipatory discriminability. On
      trials where the 2% sucrose solution was followed by an 8% sucrose solution, all
      groups showed low discriminability scores, suggesting that when two reward values
      are very similar even control animals are not able to separate the reward values
      in memory. However, the results of a preference task revealed that all groups can
      perceptually discriminate between a 2% and an 8% sucrose solution. The data
      suggest that the amygdala but not the hippocampus is involved in the separation
      of patterns based on reward value.

PMID- 11991763
TI  - Alzheimer amyloid beta-peptide inhibits the late phase of long-term potentiation
      through calcineurin-dependent mechanisms in the hippocampal dentate gyrus.
AB  - The perforant path projecting from the entorhinal cortex to the hippocampal
      dentate gyrus is a particularly vulnerable target to the early deposition of
      amyloid beta (Abeta) peptides in Alzheimer's brain. The authors previously showed
      that brief applications of Abeta at subneurotoxic concentrations suppressed the
      early-phase long-term potentiation (E-LTP) in rat dentate gyrus. The current
      study further examines the effect of Abeta on the late-phase LTP (L-LTP) in this
      area. Using multiple high-frequency stimulus trains, a stable L-LTP lasting for
      at least 3 h was induced in the medial perforant path of rat hippocampal slices.
      Bath application of Abeta(1-42) (0.2-1.0 microM) during the induction trains
      attenuated both the initial and late stages of L-LTP. On the other hand, Abeta(1
      42) perfusion within the first hour following the induction primarily impaired
      the late stage of L-LTP, which resembled the action of the protein synthesis
      inhibitor emetine. Blockade of calcineurin activity with FK506 or cyclosporin A
      completely prevented Abeta-induced L-LTP deficits. These results suggest that
      Abeta(1-42) impaired both the induction and maintenance phase of dentate L-LTP
      through calcineurin-dependent mechanisms. In the concentration range effective
      for inhibiting L-LTP, Abeta(1-42) also reduced the amplitude of NMDA receptor
      mediated synaptic currents in dentate granule cells via a postsynaptic mechanism.
      In addition, concurrent applications of Abeta(1-42) with the protein synthesis
      inhibitor caused no additive reduction of L-LTP, indicating a common mechanism
      underlying the action of both. Thus, inhibition of NMDA receptor channels and
      disruption of protein synthesis were two possible mechanisms contributing to
      Abeta-induced L-LTP impairment.

PMID- 11991764
TI  - Phthalic acid amygdalopetal lesion of the nucleus basalis magnocellularis induces
      reversible memory deficits in rats.
AB  - The basolateral amygdala (BLA) is extensively implicated in emotional learning
      and memory. The current study investigated the contribution of cholinergic
      afferents to the BLA from the nucleus basalis magnocellularis in influencing
      aversive learning and memory. Sprague-Dawley rats were given permanent unilateral
      phthalic acid (300 ng) lesions of the nucleus basalis magnocellularis and were
      chronically implanted with cannulas aimed at the ipsilateral BLA. Lesioned rats
      showed a pronounced inhibitory avoidance task retention deficit that was
      attenuated by acute posttraining infusions of the muscarinic cholinergic agonist
      oxotremorine (4 ng) or the indirect agonist physostigmine (1 microg) into the
      BLA. Continuous multiple-trial inhibitory avoidance training and testing revealed
      that lesioned rats have a mild acquisition deficit, requiring approximately 1
      additional shock to reach the criterion, and a pronounced consolidation deficit
      as indicated by a shorter latency to enter the shock compartment on the retention
      test. Because lesioned rats did not differ from sham-operated controls in
      performance on a spatial water maze task or in shock sensitivity, it is not
      likely that the memory impairments produced by the phthalic acid lesions are due
      to any general sensory or motor deficits. These findings suggest that the dense
      cholinergic projection from the nucleus basalis magnocellularis to the BLA is
      involved in both the acquisition and the consolidation of the aversive inhibitory
      avoidance task.

PMID- 11991765
TI  - Kainic acid lesions disrupt fear-mediated memory processing.
AB  - Previous research has shown that hippocampal lesions impair the expression of
      fear conditioning. This fear conditioning deficit may be due to memory impairment
      or a reduction in fear in lesioned animals. To address these possibilities, the
      authors examined unconditioned and conditioned fear in male Sprague-Dawley rats
      that had received intracerebroventricular (ICV) infusions of kainic acid (KA) 30
      days prior to testing. Animals that had received bilateral ICV infusions of KA
      (1.0 microl of 0.8 mg/ml solution per side) exhibited cell loss that was
      primarily confined to the CA3 region of the dorsal hippocampus. Kainic acid
      lesions impaired contextual and cued fear conditioning but did not affect
      unconditioned fear in a light:dark test of anxiety. Moreover, animals with KA
      lesions did not habituate to the light:dark apparatus when tested over a 3-day
      period. These data suggest that decreases in fear conditioning produced by
      hippocampal lesions reflect a memory deficit and not a lack of fear.

PMID- 11991766
TI  - Effects of electrical muscle stimulation on body composition, muscle strength,
      and physical appearance.
AB  - Electrical muscle stimulation devices (EMS) have been advertised to increase
      muscle strength, to decrease body weight and body fat, and to improve muscle
      firmness and tone in healthy individuals. This study sought to test those claims.
      Twenty-seven college-aged volunteers were assigned to either an EMS (n = 16) or
      control group (n = 11). The EMS group underwent stimulation 3 times per week
      following the manufacturer's recommendations, whereas the control group underwent
      concurrent sham stimulation sessions. Bilaterally, the muscles stimulated
      included the biceps femoris, quadriceps, biceps, triceps, and abdominals (rectus
      abdominus and obliques). An identical pre- and posttesting battery included
      measurements of body weight, body fat (via skinfolds), girths, isometric and
      isokinetic strength (biceps, triceps, quadriceps, hamstrings), and appearance
      (via photographs from the front, side, and back). EMS had no significant effect
      on the any of the measured parameters. Thus, claims relative to the effectiveness
      of EMS for the apparently healthy individual are not supported by the findings of
      this study.

PMID- 11991767
TI  - Human muscle power output during upper- and lower-body exercises.
AB  - The purpose of this study was to evaluate the use of traditional resistance
      training equipment in the measurement of muscular power. This was accomplished by
      measuring the velocity of movement through a measured distance during maximal
      effort lifts using a Smith rack. The reliability of the method was established
      using 10 male volunteers who performed both bench press and squat exercises in a
      Smith rack. Maximal power output was determined at 30, 40, 50, 60, 70, 80, and
      90% of the subject's 1 repetition maximum (1RM). Test-retest power values were
      not statistically different. Another 15 male volunteers who had previous muscle
      biopsy data from the vastus lateralis muscle performed the same maximal power
      output evaluation. There were no significant relationships between peak power
      outputs and fiber-type expressions when linear regressions were performed. The
      power curve produced by graphing power output vs. the percentage of 1RM indicates
      that peak power output occurs between 50 and 70% of 1RM for the squat and between
      40 and 60% of 1RM for the bench press. These data indicate that this method of
      evaluation of muscle power is reliable, although it is not predictive of muscle
      fiber-type percentages.

PMID- 11991768
TI  - Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and
      insulin-like growth factor 1 responses to acute resistance exercise.
AB  - Ginseng, an herbal plant, has been ingested by many athletes in Oriental regions
      of the world in order to improve stamina and to facilitate rapid recovery from
      injuries. However, adequate investigation has not been conducted to examine the
      ergogenic effects of ginseng. To examine the effects of ginseng supplements on
      hormonal status following acute resistance exercise, eight male college students
      were randomly given water (control; CON) or 20 g of ginseng root extract (GIN)
      treatment immediately after a standardized exercise bout. Venous blood samples
      were drawn before and immediately after exercise and at 4 time points during a 2
      hour recovery period. Human growth hormone, testosterone, cortisol, and insulin
      like growth factor 1 (IGF-1) levels were determined by radioimmunoassay. The
      responses of plasma hormones following ginseng consumption were not significant
      between CON and GIN treatments during the 2-hour recovery period. These results
      do not support the use of ginseng to promote an anabolic hormonal status
      following resistance exercise.

PMID- 11991769
TI  - The effects of a 10-kilometer run on muscle strength and power.
AB  - Recovery of maximal force and power following a 10-km race has not been widely
      studied in the scientific literature. Ten healthy men who were experienced
      distance runners participated in this investigation. Data were collected prerace,
      immediate postrace, and 48 hours postrace to examine the effect of a 10-km race
      on muscle force production in the lower body. Maximal peak torque was measured
      via an isokinetic dynamometer at 30 degrees, 180 degrees, and 300 degrees.s-1. A
      significant (p <or= 0.05) reduction in peak torque for knee flexion was observed
      at 30 degrees.s-1 immediately postrace. Average power of the knee flexors were
      significantly decreased immediately postrace. Total work (J) flexion performed
      over the last 17 repetitions of the 50-repetition test were significantly reduced
      from baseline values during both the immediate and 48-hour postrace tests.
      Significant reductions in peak vertical jump force remained reduced 48 hours
      postrace testing. No changes were observed for jump power after the race. These
      data indicate that only the hamstring muscle group was not fully recovered to
      perform the 50-repetition test and that force production in the vertical jump
      test was compromised 48 hours after a 10-km race. Nevertheless, it appears that
      strength and power capabilities of the 10-km runner are for the most part
      restored 48 hours after an all-out 10-km race effort. From a practical
      perspective, it appears that a minimum of 48 hours should be utilized between
      multiple trials in 10-km races at track and field meets.

PMID- 11991770
TI  - Mechanomyographic and electromyographic responses to unilateral isometric
      training.
AB  - The purpose of this investigation was to examine the effects of unilateral,
      isometric training of the forearm flexors on strength and the mechanomyographic
      (MMG) and electromyographic (EMG) responses of the biceps brachii in the trained
      and untrained limb at three joint angles. Seventeen adult females (mean age +/-
      SD = 21 +/- 2 years) were randomly assigned to a control (CTL; N=7) or a training
      (TRN; N=10) group. The TRN group performed isometric training of the non-dominant
      forearm flexors on a Cybex II Dynamometer at a joint angle such that the Cybex
      lever arm was positioned 60 degrees above the horizontal plane. The training
      consisted of 3 to 5 sets of 8, 6-second repetitions at 80% of maximal voluntary
      contraction 3 times per week for 8 weeks. The results indicated a significant
      increase in flexed arm circumference as well as isometric strength in the trained
      limb at all three joint angles. There were, however, no changes in MMG or EMG
      amplitude in the trained or untrained limb and no cross-training effect for
      strength or flexed arm circumference. These findings suggested that the increased
      strength may have been due to factors associated with hypertrophy, independent of
      neural adaptations in the biceps brachii. Furthermore, hypertrophy may have had
      counteractive effects on the MMG signal that could be responsible for the lack of
      a training-induced change in the MMG amplitude.

PMID- 11991771
TI  - Difference in the magnitude of muscle damage between maximal and submaximal
      eccentric loading.
AB  - This study compared maximal (MAX-ECC) and submaximal (50%-ECC) eccentric exercise
      of the elbow flexors. Untrained male students (n = 8) performed 3 sets of 10
      repetitions of MAX-ECC with one arm and 50%-ECC with the other arm, separated by
      4 weeks. In MAX-ECC, the elbow joint was forcibly extended from a flexed (90
      degrees ) to a full-extended position (180 degrees ) in 3 seconds while producing
      maximal force. For 50%-ECC, a dumbbell set at 50% of the maximal isometric
      strength at 90 degrees of the elbow joint was lowered from the flexed to the
      extended position in 3 seconds. Changes in indicators of muscle damage were
      compared between the bouts by a 2-way repeated-measures analysis of variance.
      Changes in isometric strength, range of motion, upper arm circumference, and
      plasma creatine kinase activity were significantly smaller and the recovery was
      significantly faster for 50%-ECC compared with MAX-ECC, although the differences
      in the changes immediately after exercise were small. It appeared that the
      magnitude of initial muscle damage was similar between the bouts; however,
      secondary damage was less after 50%-ECC.

PMID- 11991772
TI  - The effect of 5, 10, and 20 repetition maximums on the recovery of voluntary and
      evoked contractile properties.
AB  - Maximal strength training has been reported to emphasize neural adaptations. The
      main objective of this study was to detect differences in muscle activation
      between 5, 10, and 20 repetition maximum (RM) sets. Fourteen subjects performed
      elbow flexion with 5, 10, and 20RM. Subjects were tested for maximum isometric
      force (maximal voluntary contraction [MVC]), twitch amplitude (peak twitch [Pt]),
      time to peak twitch (TPT), half relaxation time ((1/2) RT), electromyography
      (EMG), and muscle activation (interpolated twitch). Subjects were tested
      preexercise and 30 seconds, 1, 2, and 3 minutes postexercise. There were no
      significant differences in MVC, muscle activation, or antagonist/agonist EMG
      after 5, 10, or 20RM. However, greater RM did have a greater detrimental effect
      on twitch properties than fewer RM. Peak twitch was significantly (p = 0.004)
      less (32.08%) for the 20 than for the 5RM, whereas TPT shortened (p < 0.05) by
      7.3 and 11.1% with 10 and 20RM vs. 5RM, respectively. Half relaxation time at
      20RM was shortened (p < 0.05) by 20.6 and 25.4% compared with that at 5 and 10RM,
      respectively. MVC, muscle activation, and temporal twitch properties did not
      recover within 3 minutes of recovery. In conclusion, whereas 5RM did not produce
      greater muscle inactivation, twitch contractile properties were affected to a
      greater degree by a higher number of RM.

PMID- 11991773
TI  - The effects of an exercise physiology program on physical fitness variables, body
      satisfaction, and physiology knowledge.
AB  - This study was performed to determine the effects of an exercise physiology
      program on physical fitness, body satisfaction, and knowledge. A total of 161
      students (mean age = 16.5 +/- 0.89 years) of the Coral Gables Senior High School
      served as the experimental group volunteers, whereas 33 students enrolled in a
      standard biology course served as the control group (mean age = 15.61 +/- 0.84
      years). The experimental group received exercise physiology theory coupled with
      active aerobic and resistance exercise. Age (p = 0.0001) and lean body mass (p =
      0.023) were the only physical characteristics significantly greater in the
      experimental group at pretesting. An analysis of covariance controlling for
      pretest values showed better results in the experimental compared with the
      control group for sit and reach (p = 0.008), step test, recovery heart rate (p =
      0.0002), overhead press (p = 0.002), bench press (p = 0.017), leg press (p =
      0.012), sit-ups (p = 0.001), body satisfaction (p = 0.0009), and physiology
      knowledge (p = 0.0001) at posttesting. Findings indicated that a biology
      curriculum integrated with exercise physiology theory and exercise activities may
      result in significant improvements in physical fitness, body size satisfaction,
      and physiology knowledge in high school adolescents.

PMID- 11991774
TI  - Standard anthropometric, body composition, and strength variables as predictors
      of jumping performance in elite junior athletes.
AB  - The aim of the study was to investigate whether variables routinely assessed
      while testing athletes can also predict movement performance. The relation
      between jumping performance and standard strength, anthropometric, and body
      composition variables was examined in elite junior basketball players. The 33
      males were tested for maximal vertical jump, as well as for maximal isometric
      voluntary force and rate of force development of hip and knee extensors. Standard
      anthropometric and body composition measures (body height, lean body mass, as
      well as the percentage of fat and muscle tissue) were also taken. Except for
      maximal isometric forces (0.38 and 0.52 N.kg(-1) for hip and knee extensors,
      respectively), all correlation coefficients between the selected variables and
      jump height were insignificant. As a consequence, the corresponding multiple
      correlation coefficient, R = 0.71, also suggested a moderate predictability of
      jumping performance by the standard strength tests and anthropometric and body
      composition variables. The results obtained dispute the use of the examined tests
      in sport performance assessment, and also question applying the tests for other
      purposes such as evaluation of training procedures or selection of young
      athletes. Therefore, the results are in line with the concept that a reliable
      performance assessment in homogeneous groups of athletes requires predominantly
      movement-specific testing.

PMID- 11991775
TI  - Relation between fitness tests and match performance in elite Italian soccer
      referees.
AB  - This study examined the relation between field-test results and match performance
      in elite Italian soccer referees. Subjects (n = 22) were all experienced elite
      level referees enrolled in the Commissione Arbitri Nazionali (CAN) and thus
      officiating in the Serie A and B Italian championships. Referees were, on
      separate occasions, tested for fitness (50-m, 200-m, and 12-minute run tests) and
      observed a minimum of 1 and a maximum of 3 times (n = 39) during Serie A matches.
      Match analyses were performed considering 11 match activity categories. Analyses
      of correlations were performed considering 50-m, 200-m, and 12-minute run test
      performances as independent variables and total distance, maximal speed distance
      (runs performed at speeds faster than 24 km.h-1), and high-intensity activity
      distance (runs performed at speeds faster than 18 km.h-1, high intensity activity
      [HIA]) as dependent variables. Statistical significance was set at p <or= 0.05.
      In the 50-m, 200-m, and 12-minute run tests the referees scored, 7.07 +/- 0.26
      seconds, 29.57 +/- 1.44 seconds, and 2866 +/- 164 m, respectively. The 12-minute
      run test showed a moderate correlation with total match distance (r = 0.71, p <
      0.05), and a low correlation with HIA and maximal speed distance (r = 0.51, p <
      0.05 and r = 0.32, p < 0.05, respectively). The 200-m and 50-m sprint times were
      not correlated with the distance covered at maximal speed or HIA, but correlated
      negatively with match distance (r = -0.48, p < 0.05 and r = -0.38, p < 0.05,
      respectively). The results of the present study demonstrate that the 12-minute
      run test is a moderate predictor of match performance in elite referees and that
      aerobic fitness should have priority in the physical conditioning programs of the
      elite soccer referee.

PMID- 11991776
TI  - Training injuries in rugby league: an evaluation of skill-based conditioning
      games.
AB  - This study investigated the site and nature of rugby league training injuries,
      and identified the training activities that were most likely to result in injury
      in rugby league players. The incidence of training injuries was prospectively
      studied in 60 semiprofessional rugby league players over 1 season. Injury data
      was collected from 72 training sessions, which included all preseason and in
      season training sessions. Injuries were described according to site, type, and
      the training activity performed at the time of injury. The majority of injuries
      (90.9 per 1000 training hours, 37.5%) were sustained in traditional conditioning
      activities that involved no skill component (i.e., running without the ball). In
      contrast, the incidence of injuries sustained while participating in skill-based
      conditioning games (26.0 per 1000 training hours, 10.7%) was low. These results
      suggest that skill-based conditioning games offer a safe, effective method of
      conditioning for rugby league players.

PMID- 11991777
TI  - Metabolic cost of aerobic dance bench stepping at varying cadences and bench
      heights.
AB  - To determine the metabolic and cardiovascular responses of aerobic dance bench
      stepping (ADBS) at commonly used cadences and bench heights, 30 women (19-47
      years of age) performed a graded maximal treadmill test and four 8-minute
      submaximal ADBS routines. Subjects followed identical videotape sequences of
      basic ADBS movements at cadences of 125 and 130 beats.min(-1) at bench heights of
      6 and 8 in. Physiological measurements were taken during each minute of each
      test. Mean values calculated from the last 3 minutes were used for data analysis.
      Although there were no physiological differences between ADBS at the 2 cadences,
      there were significant physiological differences between ADBS at the 2 bench
      heights. On average, a 2-in. increase in bench height, increased heart rate, VO2,
      and rating of perceived exertion by 10 beats.min(-1), 3.09 ml.kg(-1) min(-1), and
      1.53, respectively. In conclusion, it appears that bench height is more of a
      factor than cadence in increasing metabolic cost of ADBS. Results from this study
      provide information about the energy cost of ADBS at the common bench heights and
      cadences used in this study and, therefore, may be used to help aerobic
      participants select the proper bench height and cadence combination to control
      body weight and develop cardiorespiratory fitness safely and effectively.

PMID- 11991778
TI  - A comparison of linear and daily undulating periodized programs with equated
      volume and intensity for strength.
AB  - The purpose of this study was to compare linear periodization (LP) and daily
      undulating periodization (DUP) for strength gains. Twenty men (age = 21 +/- 2.3
      years) were randomly assigned to LP (n = 10) or DUP (n = 10) groups. One
      repetition maximum (1RM) was recorded for bench press and leg press as a pre-,
      mid-, and posttest. Training involved 3 sets (bench press and leg press), 3 days
      per week. The LP group performed sets of 8 RM during weeks 1-4, 6 RM during weeks
      4-8, and 4 RM during weeks 9-12. The DUP group altered training on a daily basis
      (Monday, 8 RM; Wednesday, 6 RM; Friday, 4 RM). Analysis of variance with repeated
      measures revealed statistically significant differences favoring the DUP group
      between T1 to T2 and T1 to T3. Making program alterations on a daily basis was
      more effective in eliciting strength gains than doing so every 4 weeks.

PMID- 11991779
TI  - Effects of prolonged and reduced warm-ups on diurnal variation in body
      temperature and swim performance.
AB  - Previous studies have suggested a diurnal variation in the performance of
      physical tasks. The theoretical basis for the effect of time-of-day on
      performance centers on the circadian rhythms of many physiological variables and
      especially the body temperature curve. This investigation had two purposes: (a)
      to determine if increasing the volume of the warm-up could eliminate diurnal
      variation in body temperature and swim performance, and (b) to determine if
      reduction of the warm-up volume in the late afternoon would affect body
      temperature and swim performance. Participants for this investigation included 6
      male and 4 female competitive swimmers (mean age = 15 +/- 1 years). Before the
      swim performance trials in the morning, participants warmed up with either
      standard volume (2,011.68 m) or 200% of that volume. Before the afternoon swim
      performance trials, warm-up volumes were either 33% or 100% of the standard warm
      up volume. Before entering the water and immediately after the warm-up,
      temperature was taken from the ear. After the swim performance, participants were
      asked to rate their perceived exertion on the basis of Borg's CR-10 rating scale.
      The order of test administration for time of day and warm-up condition was
      balanced and with tests carried out over 4 days. Each swimmer completed 1 test
      condition (warm-up) per day. Results indicated that increased morning warm-up
      time eliminated diurnal variation in body temperature; however, evening
      superiority in swimming performance was not eliminated. The results also
      indicated that reducing the volume of the afternoon warm-up to 33% of the
      standard warm-up had no effect on body temperature or swim performance.

PMID- 11991780
TI  - Effect of rotator cuff exercise on humeral rotation torque in healthy
      individuals.
AB  - Conservative management of rotator cuff pathology often involves certain
      therapeutic exercises. Although a major goal of these exercises is to increase
      strength of the rotator cuff, little empirical evidence supports this assertion.
      In this study, 34 nonpathologic young adults were pretested using a LIDO
      Multijoint II isokinetic device for average and peak torque generated during
      internal and external rotation. Subjects were arbitrarily assigned to a right-arm
      or left-arm-trained group, exercised for 4 weeks, and then posttested for
      changes in humeral rotation torque. Moderate but significant increases in torque
      (8-10%) as well as in total work done were observed in both groups, only in the
      trained arm. Subjects who trained the nondominant (left) arm experienced gains
      similar to those who trained the right arm. Gains were significant in the case of
      both internal and external rotation (also average as well as peak torque), with
      men and women experiencing the same relative increases. These data, in addition
      to supporting the use of selected exercises to increase humeral rotation torque
      in a healthy population, offer a potential model for the rehabilitation of
      patients with rotator cuff injury.

PMID- 11991781
TI  - Fitness levels of firefighter recruits before and after a supervised exercise
      training program.
AB  - Federal law prohibits pre-employment physical examination of firefighter
      recruits, but these workers must perform intense exercise in arduous
      environments. Components of physical fitness of rookie firefighters (n = 115; 104
      men, mean +/- SD: age = 28.3 +/- 4.3 years; height = 1.76 +/- 0.07 m; weight =
      83.2 +/- 13.9 kg; percent body fat = 17 +/- 8%) were measured upon being hired
      and following a 16-week exercise training program (1 h.d(-1), 3 d.wk(-1))
      designed to improve physical fitness. Maximum aerobic capacity (VO2max) was
      estimated from submaximal cycle ergometry, body composition from skinfold tests,
      flexibility from a sit and reach test, strength by hand grip dynamometry, and
      muscle endurance by a push-up test. The results are as follows (*, p <or= 0.007
      vs. pretraining): VO2max increased by 28% (35 +/- 7 to 45 +/- 6* ml.kg(-1).min(
      1), 88 +/- 20 to 113 +/- 17%* of predicted increase); muscle endurance increased
      (41 +/- 13 to 51 +/- 14* push-ups); flexibility increased (0.34 +/- 0.07 to 0.35
      +/- 0.07* m); muscle strength tended to increase (102.9 +/- 18.7 to 105.4 +/-
      18.7 kg, p = 0.06); body weight tended to decrease (83.2 +/- 13.9 to 82.7 +/-
      13.2 kg, p = 0.06); lean tissue weight increased (68.8 +/- 9.9 to 69.9 +/- 9.5*
      kg); and fat weight decreased (14.6 +/- 8.0 to 13.0 +/- 7.1* kg). We concluded
      that aerobic capacity was 20% lower before training than that deemed sufficient
      for safe performance of fire suppression duties; that training improved aerobic
      capacity by 28%, decreased fat and increased lean tissue weight, and
      increased/tended to increase other components of physical fitness. Prior to
      initiation of this training program, aerobic capacity of these firefighters was
      below that deemed appropriate for performing fire suppression duties. Training
      resulted in a large increase in aerobic capacity, so that the trainees ended the
      program with an aerobic capacity considered appropriate for fighting fires. It is
      hoped that the results of this study will encourage those who oversee workers who
      are responsible for the public's safety to mandate assessment of physical fitness
      of new hires, with mandatory participation in exercise training for those new
      hires who are found to possess less than appropriate aerobic capacity.

PMID- 11991782
TI  - The effect of experience and gender on cardiovascular and metabolic responses
      with dynamic Tae Kwon Do exercise.
AB  - This study, conducted at the Exercise Physiology Laboratory of Auburn University,
      AL, addressed and compared the acute cardiovascular and metabolic effects
      elicited by novice and experienced men and women participants during a single
      bout of dynamic Tae Kwon Do exercise and investigated whether or not dynamic Tae
      Kwon Do practice is an exercise modality that provides sufficient
      cardiorespiratory demand for enhancing aerobic fitness and promoting weight and
      fat loss. Twenty-eight men and women (aged 19-42) were assigned to 1 of the
      following 4 groups: Tae Kwon Do experienced and trained men (ME), Tae Kwon Do
      experienced and trained women (FE), novice Tae Kwon Do men (MN), and novice Tae
      Kwon Do women (FN). The results of this investigation indicate that this form of
      exercise can be performed for an extended period of 20 minutes. All 4 groups
      achieved the recommended stimulus for effective initiation of cardiovascular
      adaptations and conditioning. The mean exercise heart rate responses (88.3-92.2%
      of maximal heart rate [HR max]) were similar for all groups. The observed
      exercise intensity ranged from 67.9 to 72.1% VO2max, and no significant
      difference based on the experience and gender and exercise oxygen uptake could be
      established. Data in this study indicate a high caloric expenditure for this mode
      of exercise. Total caloric cost of 20 minutes of dynamic Tae Kwon Do, 194.8 and
      201.6 kcal for novice women and experienced women, respectively, was
      significantly lower in comparison with that of their men counterparts (316.5 and
      286.5 kcal, respectively), but no significant relationship between experience and
      energy cost was found. The conclusion of this study indicates that dynamic Tae
      Kwon Do is an exercise modality that can be appropriately prescribed for
      cardiovascular conditioning, weight control, and fat loss.

PMID- 11991783
TI  - Effect of exercise at three exercise intensities on salivary cortisol.
AB  - Changes in cortisol concentration in response to exercise at 3 different
      intensities were quantified. Ten apparently healthy, recreationally active males
      participated. On 4 separate occasions, subjects were assigned a random order of 1
      hour cycle ergometer bouts of exercise at 44.5 +/- 5.5%, 62.3 +/- 3.8%, and 76.0
      +/- 6.0% (mean +/- SD) of VO2peak and a resting control session. Saliva samples
      were collected before exercise at 10, 20, 40, and 59 minutes of exercise and at
      20 minutes of recovery. Differences in cortisol concentration were assessed via
      multivariate analysis of variance (alpha = 0.05) Tukey post hoc analysis when
      indicated. During the highest-intensity exercise session, cortisol was
      significantly higher at 59 minutes of exercise (p = 0.004) and at 20 minutes of
      recovery (p = 0.016) than at those same time points during the resting control
      session. No significant differences in cortisol concentration were noted among
      resting, low-, and moderate-intensity exercise. Exercise <40 minutes in duration
      elicited no significant differences at any intensity. These data indicate that
      only exercise of high intensity and long duration results in significant
      elevations of salivary cortisol.

PMID- 11991784
TI  - Biomechanical analysis of the knee during the power clean.
AB  - To our knowledge, no scientific literature has examined the 3-dimensional forces
      acting at the knee joint during a power clean. Ten male weightlifting subjects
      (25.9 years, SD 3.54) performed 1 set of the power clean at 60 and 70% of their
      maximal collegiate level for 5 repetitions. The subjects displayed a large
      compressive, moderate anterior, and a small degree of lateral and medial force at
      the knee during both percentage lifts. The majority of these forces occurred
      during the second pull phase or the catching phase of the lift. Lifters with
      decreased weight/system weight percentages displayed a more efficient lift that
      placed less stress on the knees. This analysis may provide invaluable information
      in the assessment of weight percentages used for Olympic weightlifters throughout
      the training year. the power clean.

PMID- 11991785
TI  - Reliability and validity of two isometric squat tests.
AB  - The purpose of the present study was first to examine the reliability of
      isometric squat (IS) and isometric forward hack squat (IFHS) tests to determine
      if repeated measures on the same subjects yielded reliable results. The second
      purpose was to examine the relation between isometric and dynamic measures of
      strength to assess validity. Fourteen male subjects performed maximal IS and IFHS
      tests on 2 occasions and 1 repetition maximum (1-RM) free-weight squat and
      forward hack squat (FHS) tests on 1 occasion. The 2 tests were found to be highly
      reliable (intraclass correlation coefficient [ICC](IS) = 0.97 and ICC(IFHS) =
      1.00). There was a strong relation between average IS and 1-RM squat performance,
      and between IFHS and 1-RM FHS performance (r(squat) = 0.77, r(FHS) = 0.76; p <
      0.01), but a weak relation between squat and FHS test performances (r < 0.55).
      There was also no difference between observed 1-RM values and those predicted by
      our regression equations. Errors in predicting 1-RM performance were in the order
      of 8.5% (standard error of the estimate [SEE] = 13.8 kg) and 7.3% (SEE = 19.4 kg)
      for IS and IFHS respectively. Correlations between isometric and 1-RM tests were
      not of sufficient size to indicate high validity of the isometric tests. Together
      the results suggest that IS and IFHS tests could detect small differences in
      multijoint isometric strength between subjects, or performance changes over time,
      and that the scores in the isometric tests are well related to 1-RM performance.
      However, there was a small error when predicting 1-RM performance from isometric
      performance, and these tests have not been shown to discriminate between small
      changes in dynamic strength. The weak relation between squat and FHS test
      performance can be attributed to differences in the movement patterns of the
      tests

PMID- 11991786
TI  - Preliminary investigation: the impact of the NCAA Wrestling Weight Certification
      Program on weight cutting.
AB  - Historically, wrestling is a sport dependent on weight. Three tragic deaths in
      late 1997 prompted the National Collegiate Athletic Association (NCAA) to make a
      Wrestling Weight Certification Program (WWCP) mandatory to foster a safe
      competitive environment. One institution examined the impact of this program on
      weight cutting. Thirty-two NCAA Division I wrestlers completed the WWCP in the
      1998-1999 season and 29 in 1999-2000. Eighteen (56%) of 32 wrestlers in 1998-1999
      weighed in 10 or more pounds above the previous year's competition weight.
      Whereas, 28% weighed in 20 or more pounds above the previous year's competition
      weight. Weekly weight loss for the wrestlers in 1998-1999 revealed a substantial
      loss during the first week, possibly demonstrating the use of time-tested
      techniques for weight loss. However, in 1999-2000, the first week weight loss was
      less pronounced, with 65.8% of the weight being lost during the second half of
      the WWCP. Therefore, these wrestlers may be breaking the sport historic cycle of
      weight fluctuations through the WWCP.

PMID- 11991787
TI  - Physiological profile of an elite freestyle wrestler preparing for competition: a
      case study.
AB  - The purpose of the present investigation was to describe the physiological
      changes of a nationally ranked older elite freestyle wrestler during a 7-month
      observation period as he prepared for the 2000 Olympic freestyle wrestling
      trials. A 33-year-old male wrestler was evaluated 3 times during the study for
      measurements of body composition, resting energy expenditure, maximal oxygen
      consumption, isometric strength, anaerobic power and capacity, nutritional
      intake, and various serum plasma constituents. Body weight decreased by 1 kg,
      which consisted of fat-free mass (FFM), whereas body fat remained stable at 5.8%.
      Muscular strength and aerobic power were maintained throughout the study.
      Measures of anaerobic work capacity tended to be higher and blood lactate lower
      as the subject progressed throughout the investigation. All serum plasma
      constituents were within clinically normal ranges and remained relatively stable.
      Despite a small loss of FFM, the subject was able to maintain muscular strength
      and aerobic fitness while concomitantly enhancing anaerobic capacity and power
      capabilities throughout the study period as he prepared for the 2000 Olympic
      freestyle wrestling trials.

PMID- 11991788
TI  - Isokinetic leg strength of institutionalized older adults with mental retardation
      with and without Down's syndrome.
AB  - This study compared isokinetic leg strength of aged individuals with mental
      retardation (MR) with and without Down's syndrome (DS). Nine subjects with MR and
      DS (mean age = 61) and 16 subjects with MR but without DS (mean age = 63)
      performed a leg strength test on a Biodex dynamometer. Parameters measured were
      peak torque, peak torque percent body weight (ratio displayed as a percentage of
      the maximum torque production to the subject's body weight), and average power
      percent body weight. In addition, anthropometric measurements (height, weight,
      skinfolds, and body mass index) and intelligence quotient (IQ) were also analyzed
      and compared. The results indicate a significant increase of scores for
      isokinetic knee extension and flexion in the group with MR but without DS over
      the subjects in the group with MR and DS. As a group, the individuals with MR and
      DS tended to be smaller and fatter. No significant difference in IQ was observed
      between the 2 groups with MR. It was concluded that the strength of individuals
      with MR but without DS is greater than the group of subjects with MR and DS. When
      comparing their results to aged individuals without MR, a significant decline in
      muscle strength can be observed among people with MR.

PMID- 11991789
TI  - The thunder of hooves in a tunnel.

PMID- 11991790
TI  - Mitochondrial factors in the pathogenesis of diabetes: a hypothesis for
      treatment.
AB  - A growing body of evidence has demonstrated a link between various disturbances
      in mitochondrial functioning and type 2 diabetes. This review focuses on a range
      of mitochondrial factors important in the pathogenesis of this disease. The
      mitochondrion is an integral part of the insulin system found in the islet cells
      of the pancreas. Because of the systemic complexity of mitochondrial functioning
      in terms of tissue and energetic thresholds, details of structure and function
      are reviewed. The expression of type 2 diabetes can be ascribed to a number of
      qualitative or quantitative changes in the mitochondria. Qualitative changes
      refer to genetic disturbances in mitochondrial DNA (mtDNA). Heteroplasmic as well
      as homoplasmic mutations of mtDNA can lead to the development of a number of
      genetic disorders that express the phenotype of type 2 diabetes. Quantitative
      decreases in mtDNA copy number have also been linked to the pathogenesis of
      diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed
      the influence of the mitochondria on nuclear-encoded glucose transporters and the
      influence of nuclear encoded uncoupling proteins on the mitochondria. This basic
      research into the pathogenesis of diabetes has led to the awareness of natural
      therapeutics (such as coenzyme Q10) that increase mitochondrial functioning and
      avoidance of trans-fatty acids that decrease mitochondrial functioning.

PMID- 11991791
TI  - Estrogen metabolism and the diet-cancer connection: rationale for assessing the
      ratio of urinary hydroxylated estrogen metabolites.
AB  - Estrogens are known for their proliferative effects on estrogen-sensitive tissues
      resulting in tumorigenesis. Results of experiments in multiple laboratories over
      the last 20 years have shown that a large part of the cancer-inducing effect of
      estrogen involves the formation of agonistic metabolites of estrogen, especially
      16-alpha-hydroxyestrone. Other metabolites, such as 2-hydroxyestrone and 2
      hydroxyestradiol, offer protection against the estrogen-agonist effects of 16
      alpha-hydroxyestrone. An ELISA method for measuring 2- and 16-alpha-hydroxylated
      estrogen (OHE) metabolites in urine is available and the ratio of urinary 2
      OHE/16-alpha-OHE (2/16-alpha ratio) is a useful biomarker for estrogen-related
      cancer risk. The CYP1A1 enzyme that catalyzes 2-hydroxyestrone (2-OHE1) formation
      is inducible by dietary modification and supplementation with the active
      components of cruciferous vegetables, indole-3-carbinol (I-3-C), or
      diindolylmethane (DIM). Other dietary components, especially omega-3
      polyunsaturated fatty acids and lignans in foods like flax seed, also exert
      favorable effects on estrogen metabolism. Thus, there appear to be effective
      dietary means for reducing cancer risk by improving estrogen metabolism. This
      review presents the accumulated evidence to help clinicians evaluate the merit of
      using tests that measure estrogen metabolites and using interventions to modify
      estrogen metabolism.

PMID- 11991792
TI  - The importance of pharmacological synergy in psychoactive herbal medicines.
AB  - The therapeutic effects of many herbal medicines have been well established;
      however, definitive mechanisms of action remain to be elucidated for many
      psychoactive herbal medications. Although several mechanisms have been
      identified, they are often insufficient to account for the observed effects of
      the plant or its extracts. This review emphasizes that, in addition to searching
      for more potent mechanisms, one must consider the additive and supra-additive
      effects of a plant's multiple constituents. Synergy may occur through
      pharmacokinetic and/or pharmacodynamic interactions. Examples are given that
      illustrate synergistic actions in St. John's wort (Hypericum perforatum), kava
      kava (Piper methysticum), and valerian (Valeriana officinalis).

PMID- 11991793
TI  - Immunological activity of larch arabinogalactan and Echinacea: a preliminary,
      randomized, double-blind, placebo-controlled trial.
AB  - The immunomodulating effects of two Echinacea species, E. purpurea and E.
      angustifolia and larch arabinogalactan extracted from Larix occidentalis were
      examined in a randomized, double-blind, placebo-controlled, prospective four-week
      clinical trial at a naturopathic medical school research center.
      SUBJECTS/MATERIALS: Forty-eight healthy female volunteers (22-51 y) were randomly
      assigned to one of six groups: standardized extract of E. purpurea (EP); ultra
      refined E. purpurea/E. angustifolia (urEPA); E. purpurea/E. angustifolia (EPA);
      E. purpurea/E. angustifolia plus larch arabinogalactan (EPALA); larch
      arabinogalactan (LA); or placebo. METHODS: Immunological tests with enumerative
      measurements, stool cultures for Lactobacillus acidophilus and yeast, and health
      related quality of life (HRQoL) using the Medical Outcomes Study derived SF-36
      self-administered questionnaire were assessed at baseline and at four weeks.
      RESULTS: Complement properdin increased by 21 percent in the EPA group (p<0.05)
      and by 18 percent in the EPALA group (p<0.05), compared to the placebo group
      (p>0.05). SF-36 showed improvements in overall physical health, vitality, and
      emotional health in the same two groups (EPA and EPALA). DISCUSSION: Volunteers
      in the EPA and EPALA groups had increased production of complement properdin
      after four weeks of intervention. The increased complement properdin may be an
      indication of one aspect of immune system stimulation in patients treated with
      either E. purpurea/E. angustifolia or E. purpurea/E. angustifolia plus larch
      arabinogalactan.

PMID- 11991794
TI  - Phosphatidylcholine.

PMID- 11991795
TI  - Plantago ovata. (Psyllium).

PMID- 11991796
TI  - The right to be a patient.

PMID- 11991797
TI  - Effect of duration of upper- and lower-extremity rehabilitation sessions and
      walking speed on recovery of interlimb coordination in hemiplegic gait.
AB  - BACKGROUND AND PURPOSE: The effects of different durations of rehabilitation
      sessions for the upper extremities (UEs) and lower extremities (LEs) on the
      recovery of interlimb coordination in hemiplegic gait in patients who have had a
      stroke were investigated. SUBJECTS AND METHODS: Fifty-three subjects who had
      strokes involving their middle cerebral arteries were assigned to rehabilitation
      programs with (1) an emphasis on the LEs, (2) an emphasis on the paretic UE, or
      (3) a condition in which the paretic arm (UE) and leg (LE) were immobilized with
      an inflatable pressure splint (control treatment). The 3 treatment regimens were
      applied for 30 minutes, 5 days a week, during the first 20 weeks after onset of
      stroke. All subjects also participated in a rehabilitation program 5 days a week
      that consisted of 15 minutes of UE exercises and 15 minutes of LE exercises in
      addition to a weekly 11/2-hour session of training in activities of daily living.
      A repeated-measures design was used. Differences among the 3 treatment regimens
      were evaluated in terms of comfortable and maximal walking speeds. In addition,
      mean continuous relative phase (CRP) between paretic arm and leg (PAL) movements
      and nonparetic arm and leg (NAL) movements and standard deviations of CRP of both
      limb pairs as a measurement of stability (variability) were evaluated. RESULTS:
      Comfortable walking speed improved in the group that received interventions
      involving the LEs compared with the group that received interventions involving
      the UEs and the group that received the control treatment. No differences among
      the 3 treatment conditions were found for the mean CRP of NAL and PAL as well as
      the standard deviation of CRP of both limb pairs. DISCUSSION AND CONCLUSION: With
      the exception of an improved comfortable walking speed as a result of a longer
      duration of rehabilitation sessions, no differential effects of duration of
      rehabilitation sessions for the LEs and UEs on the variable we measured related
      to hemiplegic gait were found. Increasing walking speed, however, resulted in a
      larger mean CRP for both limb pairs, with increased stability and asymmetry of
      walking, indicating that walking speed influences interlimb coordination in
      hemiplegic gait.

PMID- 11991798
TI  - The influence of a move to program management on physical therapist practice.
AB  - BACKGROUND AND PURPOSE: The purpose of this qualitative study was to examine how
      a move to program management (PM) from a traditional department structure
      affected the professional practice of physical therapists in a large Canadian
      teaching hospital. SUBJECTS: Twenty-five physical therapists participated in 1 of
      5 focus groups, and 4 physical therapists participated in individual interviews.
      METHODS: Focus groups and structured interviews were conducted by an experienced
      facilitator who was not a physical therapist. All focus groups and interviews
      were audiotaped and transcribed. Using an open-coding technique, 2 investigators
      undertook line-by-line analysis of each transcript to identify and code specific
      events related to the physical therapists' experiences. The investigators reached
      a consensus on all coding categories and then identified themes. RESULTS: Seven
      themes that addressed issues of affect (a sense of loss, low morale, and positive
      coping), professional practice (loss of professional development activities,
      professional advantages, the assuming of multiple roles), and patient care were
      identified. DISCUSSION AND CONCLUSION: Physical therapists who were deployed from
      a department to a program described both positive and negative effects of the
      move to PM on their practice. There were reported influences on their personal
      affect, professional practice, and patient care. Staff and physical therapy
      administrators need to be aware of potential implications of an organization's
      move to PM on the professional practice of frontline staff.

PMID- 11991799
TI  - Work-related musculoskeletal disorders and the culture of physical therapy.
AB  - BACKGROUND AND PURPOSE: Knowledge, skills, relationships, and attitudes of caring
      and working hard are all thought to be valued by physical therapists. This
      article explores how physical therapists see themselves, in light of some of
      these values, when they experience work-related musculoskeletal disorders
      (WMSDs). The article also explores the ways in which these values may compete
      with each other, and it suggests how this may contribute to the onset of WMSDs
      and to therapists' behavior following a WMSD. SUBJECTS AND METHODS: Eighteen
      therapists who had made a career change after a WMSD participated in interviews
      that were designed to gain insight into the attitudes and beliefs of therapists
      who had had a WMSD. RESULTS: Participants did not anticipate WMSDs, and they
      typically believed their physical therapy knowledge and skills would have
      prevented WMSDs from occurring. They saw themselves as knowledgeable and caring
      and indicated that these characteristics were highly valued by the profession.
      Their need to demonstrate these attributes sometimes resulted in behaviors that
      contributed to the development of their WMSDs and made them worse after their
      onset. DISCUSSION AND CONCLUSION: The cultural values of physical therapists may
      make it difficult for them to do their jobs in a way that minimizes the risk of
      WMSDs. The study identified a potential conflict between the therapists' need to
      (1) demonstrate their ability to work hard and care for their patients and (2)
      appear knowledgeable and skilled by remaining injury free.

PMID- 11991800
TI  - Rehabilitation for balance and ambulation in a patient with attention impairment
      due to intracranial hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of this case report is to describe physical
      therapy to improve the balance and ambulation of a 16-year-old patient with
      attention impairment following intracranial hemorrhage. CASE DESCRIPTION: The
      patient initially had frequent losses of balance, especially in distracting
      environments, due in part to decreased attention. He was managed with a balance
      and ambulation training program that incorporated the principles of cognitive
      rehabilitation for attention impairments. OUTCOMES: Following 11 weeks of
      outpatient therapy, the patient returned to independent ambulation at school
      without losses of balance. DISCUSSION: Research is needed to determine the
      interaction between balance and attention in patients with brain injury and
      effective treatment for patients with decreased balance related to attention
      impairments.

PMID- 11991801
TI  - Supported treadmill training for gait and balance in a patient with progressive
      supranuclear palsy.
AB  - BACKGROUND AND PURPOSE: Impaired balance, gait disturbances, and frequent falls
      are common problems in people with progressive supranuclear palsy (PSP). This
      case report describes the use of a modified body weight support treadmill
      training program to reduce falls and improve the balance and gait of a patient
      with PSP. CASE DESCRIPTION: The patient was a 62-year-old man diagnosed with PSP.
      His major problems were impaired balance and frequent, abrupt falls. METHODS:
      Physical therapy included walk training, balance perturbation, and step training
      using body weight support with a treadmill. Training sessions lasted 11/2 hours
      and occurred 3 days a week for 8 weeks. Fall incidence, balance, and gait were
      assessed before, during, and after the program. OUTCOMES: The patient reported
      fewer falls during and after training. Balance and gait improved after training.
      DISCUSSION: This case report is the first to report fall reduction, improved
      gait, and improved balance following physical therapy for a person with PSP.

PMID- 11991802
TI  - Brain tumors.

PMID- 11991803
TI  - Roland-Morris scale reliability.

PMID- 11991804
TI  - Mu-class glutathione transferase from Xenopus laevis: molecular cloning,
      expression and site-directed mutagenesis.
AB  - A cDNA encoding a Mu-class glutathione transferase (XlGSTM1-1) has been isolated
      from a Xenopus laevis liver library, and its nucleotide sequence has been
      determined. XlGSTM1-1 is composed of 219 amino acid residues with a calculated
      molecular mass of 25359 Da. Unlike many mammalian Mu-class GSTs, XlGSTM1-1 has a
      narrow spectrum of substrate specificity and it is also less effective in
      conjugating 1-chloro-2,4-dinitrobenzene. A notable structural feature of XlGSTM1
      1 is the presence of the Cys-139 residue in place of the Glu-139, as well as the
      absence of the Cys-114 residue, present in other Mu-class GSTs, which is replaced
      by Ala. Site-directed mutagenesis experiments indicate that Cys-139 is not
      involved in the catalytic mechanism of XlGSTM1-1 but may be in part responsible
      for its structural instability, and experiments in vivo confirmed the role of
      this residue in stability. Evidence indicating that Arg-107 is essential for the
      1-chloro-2,4-dinitrobenzene conjugation capacity of XlGSTM1-1 is also presented.

PMID- 11991806
TI  - Long-term vitamin E supplementation fails to reduce lipid peroxidation in people
      at cardiovascular risk: analysis of underlying factors.
AB  - BACKGROUND: Antioxidant supplementation with vitamin E had no effect in the
      prevention of cardiovascular diseases (CVD) in three recent large, randomized
      clinical trials. In order to reassess critically the role of vitamin E in CVD
      prevention, it is important to establish whether these results are related to a
      lack of antioxidant action. METHODS: We examined the in vivo antioxidant effect
      of vitamin E (300 mg/day for about three years) in 144 participants in the
      Primary Prevention Project (females and males, aged >/= 50 y, with at least one
      major CV risk factor, but no history of CVD). Urinary 8-epi-PGF2alpha
      (isoprostane F2alpha-III or 15-F2t-isoP), a validated biomarker of lipid
      peroxidation, was measured by mass spectrometry. RESULTS: Urinary excretion of 8
      epi-PGF2alpha [pg/mg creatinine, median (range)] was 141 (67-498) in treated and
      148 (76-561) in untreated subjects (p = 0.10). Taking into account possible
      confounding variables, multiple regression analysis confirmed that vitamin E had
      no significant effect on this biomarker. Levels of 8-epi-PGF2alpha were in the
      normal range for most subjects, except smokers and those with uncontrolled blood
      pressure or hyperglycemia. CONCLUSIONS: Prolonged vitamin E supplementation did
      not reduce lipid peroxidation in subjects with major cardiovascular risk factors.
      The observation that the rate of lipid peroxidation was near normal in a large
      proportion of subjects may help explain why vitamin E was not effective as an
      antioxidant in the PPP study and was ineffective for CVD prevention in large
      scale trials.

PMID- 11991805
TI  - Loss of the Nrf2 transcription factor causes a marked reduction in constitutive
      and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1,
      Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice.
AB  - Mice that lack the Nrf2 basic-region leucine-zipper transcription factor are more
      sensitive than wild-type (WT) animals to the cytotoxic and genotoxic effects of
      foreign chemicals and oxidants. To determine the basis for the decrease in
      tolerance of the Nrf2 homozygous null mice to xenobiotics, enzyme assay, Western
      blotting and gene-specific real-time PCR (TaqMan) have been used to examine the
      extent to which hepatic expression of GSH-dependent enzymes is influenced by the
      transcription factor. The amounts of protein and mRNA for class Alpha, Mu and Pi
      glutathione S-transferases were compared between WT and Nrf2 knockout (KO) mice
      of both sexes under both constitutive and inducible conditions. Among the class
      Alpha and class Mu transferases, constitutive expression of Gsta1, Gsta2, Gstm1,
      Gstm2, Gstm3, Gstm4 and Gstm6 subunits was reduced in the livers of Nrf2 mutant
      mice to between 3% and 60% of that observed in WT mice. Induction of these
      subunits by butylated hydroxyanisole (BHA) was more marked in WT female mice than
      in WT male mice. TaqMan analyses showed the increase in transferase mRNA caused
      by BHA was attenuated in Nrf2(-/-) mice, with the effect being most apparent in
      the case of Gsta1, Gstm1 and Gstm3. Amongst class Pi transferase subunits, the
      constitutive hepatic level of mRNA for Gstp1 and Gstp2 was not substantially
      affected in the KO mice, but their induction by BHA was dependent on Nrf2; this
      was more obvious in female mutant mice than in male mice. Nrf2 KO mice exhibited
      reduced constitutive expression of the glutamate cysteine ligase catalytic
      subunit, and, to a lesser extent, the expression of glutamate cysteine ligase
      modifier subunit. Little variation was observed in the levels of glutathione
      synthase in the different mouse lines. Thus the increased sensitivity of Nrf2(-/
      ) mice to xenobiotics can be partly attributed to a loss in constitutive
      expression of multiple GSH-dependent enzymes, which causes a reduction in
      intrinsic detoxification capacity in the KO animal. These data also indicate that
      attenuated induction of GSH-dependent enzymes in Nrf2(-/-) mice probably accounts
      for their failure to adapt to chronic exposure to chemical and oxidative stress.

PMID- 11991807
TI  - Pooling, meta-analysis, and the evaluation of drug safety.
AB  - BACKGROUND: The "integrated safety report" of the drug registration files
      submitted to health authorities usually summarizes the rates of adverse events
      observed for a new drug, placebo or active control drugs by pooling the safety
      data across the trials. Pooling consists of adding the numbers of events observed
      in a given treatment group across the trials and dividing the results by the
      total number of patients included in this group. Because it considers treatment
      groups rather than studies, pooling ignores validity of the comparisons and is
      subject to a particular kind of bias, termed "Simpson's paradox." In contrast,
      meta-analysis and other stratified analyses are less susceptible to bias.
      METHODS: We use a hypothetical, but not atypical, application to demonstrate that
      the results of a meta-analysis can differ greatly from those obtained by pooling
      the same data. In our hypothetical model, a new drug is compared to 1) a placebo
      in 4 relatively small trials in patients at high risk for a certain adverse event
      and 2) an active reference drug in 2 larger trials of patients at low risk for
      this event. RESULTS: Using meta-analysis, the relative risk of experiencing the
      adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12])
      compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling
      the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07;
      13.08]. CONCLUSIONS: Because these findings could mislead health authorities and
      doctors, regulatory agencies should require meta-analyses or stratified analyses
      of safety data in drug registration files.

PMID- 11991808
TI  - Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic
      lateral sclerosis (ALS).
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive lethal disorder
      of large motor neurons of the spinal cord and brain. In approximately 20% of the
      familial and 2% of sporadic cases the disease is due to a defect in the gene
      encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The
      underlying molecular defect is known only in a very small portion of the
      remaining cases and therefore involvement of other genes is likely. As SOD1
      receives copper, essential for its normal function, by the copper chaperone, CCS
      (Copper Chaperone for SOD), we considered CCS as a potential candidate gene for
      ALS. RESULTS: We have characterized the genomic organization of CCS and
      determined exon-intron boundaries. The 823 bp coding region of the CCS is
      organized in 8 exons. We have evaluated involvement of the CCS in ALS by
      sequencing the entire coding region for mutations in 20 sporadic ALS patients.
      CONCLUSIONS: No causative mutations for the ALS have been detected in the CCS
      gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide
      polymorphism has been identified.

PMID- 11991809
TI  - Preferences of Mexican anesthesiologists for vecuronium, rocuronium, or other
      neuromuscular blocking agents: a survey.
AB  - BACKGROUND: Several neuromuscular blocking (NMB) agents are available for
      clinical use in anesthesia. The present study was performed in order to identify
      preferences and behaviors of anesthesiologists for using vecuronium, rocuronium
      or other NMB agents in their clinical practice. MATERIAL AND METHODS: The cross
      sectional survey was applied at the Updated Course of the Colegio Mexicano de
      Anestesiologia performed last year. Of 989, 282 (28.5%) surveys were returned.
      RESULTS: Most anesthesiologists were working at both public and private
      hospitals, performed anesthetic procedures for hospitalized and ambulatory
      patients, and anesthetized children as well as adults. Respondents did not
      consider mechanomyography as the gold standard method for neuromuscular
      monitoring. The T25 was not recognized as a pharmacodynamic parameter that
      represents the clinical duration of the neuromuscular block. Most answered that
      vecuronium induces less histamine release than rocuronium, had never used any
      neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and
      preferred rocuronium in multiple-sampling vials and vecuronium in either a vial
      for single or multiple sampling. Rocuronium was preferred for emergency surgery
      in patients with full stomach only. Almost all of anesthesiologists that conserve
      the unused drug did it without refrigeration and more than 30% conserve the
      unused drug in one syringe for further use. CONCLUSION: Vecuronium was preferred
      for most clinical situations, and the decision for this choice was not based on
      costs. Storage of unused drugs without refrigeration in a single syringe for
      purpose of future use in several patients represented a dangerous common
      practice.

PMID- 11991810
TI  - Worldwide trends in mortality from biliary tract malignancies.
AB  - BACKGROUND: Intrahepatic cholangiocarcinomas are malignant tumors arising from
      the intrahepatic biliary tract. The pathogenesis of these tumors remains unknown.
      Although there is a marked global variation in prevalence, some recent studies
      have suggested an increase in mortality from intrahepatic cholangiocarcinoma in
      several regions of low endemicity. As the study of mortality trends may yield
      clues to possible etiological factors, we analyzed worldwide time trends in
      mortality from biliary tract malignancies. METHODS: Annual age-standardized rates
      for individual countries were compiled for deaths from biliary tract malignancies
      using the WHO database. These data were used to analyze gender and site-specific
      trends in mortality rates. RESULTS: An increasing trend for mortality from
      intrahepatic cholangiocarcinoma was noted in most countries. The average
      estimated annual percentage change (EAPC) in mortality rates for males was 6.9 +/
      1.5, and for females was 5.1 +/- 1.0. Increased mortality rates were observed in
      all geographic regions. Within Europe, increases were higher in Western Europe
      than in Central or Northern Europe. In contrast, mortality rates for extrahepatic
      biliary tract malignancies showed a decreasing trend in most countries, with an
      overall average EAPC of -0.3 +/- 0.4 for males, but -1.3 +/- 0.4 for females.
      CONCLUSIONS: There has been a marked global increase in mortality from
      intrahepatic, but not extra-hepatic, biliary tract malignancies.

PMID- 11991811
TI  - Comparative assessment expression of the inhibitor of growth 1 gene (ING1) in
      normal and neoplastic tissues.
AB  - Studies have indicated that the tumor suppressor p33(ING1b) (13q33-34) interact
      with p53. Moreover, the association of functional protein forms of each member of
      the p33(ING1b)/p53 complex is essential for optimum activity of p53. The present
      report describes the sequencing of cDNAs corresponding to the p33(ING1b) mRNAs in
      a series of normal and tumor cell lines, and the production of monoclonal
      antibodies (MAbs) reactive with p33(ING1b). These antibodies were subsequently
      used to analyze p33(ING1b) expression in normal and tumor cell lines and tissues.
      No evidence of mutation of p33(ING1b) was found in any of the 15 tumor cell lines
      cDNAs studied. Our investigation of a wide range of normal tissues have shown
      that expression of the nuclear epitope is highly ubiquitous, whereas expression
      of the cytoplasmic form could be detected in only 50% of tissues studied.
      Considering neoplastic tissues, loss of nuclear p33(ING1b) was observed in
      melanoma, seminoma, papillary thyroid carcinoma, ductal breast carcinoma, and
      acute lymphoblastic leukemia. As with normal tissue, cytoplasmic p33(ING1b) was
      more restricted, being observed in around 30% of neoplastic tissues, but in
      melanoma, papillary thyroid carcinoma, ductal breast carcinoma, there was
      increased detection of cytoplasmic p33(ING1b) associated with concomitant loss of
      nuclear expression. These results may suggest that at least in some tumors, loss
      of effective p33(ING1b) function may be achieved by translocation to the
      cytoplasm or failure of nuclear localization.

PMID- 11991812
TI  - Stable, genetically engineered F(ab')(2) fragments of chimeric TNT-3 expressed in
      mammalian cells.
AB  - F(ab')(2) fragments are desirable structural derivatives of monoclonal antibodies
      (MAbs) because of their pharmacokinetic properties and bivalent binding to
      antigen. Production of these fragments, however, has proven difficult because of
      the variable sensitivity of intact antibodies to proteolytic enzymes, which can
      result in very low yields and unstable product. To circumvent these problems, we
      attempted to apply genetic engineering methods to generate stable F(ab')(2)
      fragments in NSO murine myeloma cells using the glutamine synthase expression
      system. For these studies, the chimeric MAb, chTNT-3, directed against necrotic
      regions of solid tumors, was used to generate several F(ab')(2) variants, which
      contained between one and three cysteine residues at the end of the hinge region.
      In addition, two different affinity tags (his tag, streptactin tag) were used
      with each variant to determine the best tag for purification procedures.
      Stability was measured by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and by antigen binding studies and the constructs were
      tested in vivo to measure their pharmacokinetic properties and biodistribution in
      normal organs and tumor. The results of these studies show that 3 cysteine
      residues are required to produce stable F(ab')(2) fragments and that either
      purification tag can be used with this variant to produce suitable reagents for
      in vivo studies. Those constructs containing one or two cysteines were found to
      be unstable and broke down to Fab fragments regardless of the purification tag
      used. These studies demonstrate that stable, clinically useful F(ab')(2)
      fragments of chTNT-3 can be produced in mammalian cells by genetic engineering
      methods.

PMID- 11991813
TI  - Differential V gene expression detected in the immune response to Streptococcus
      pneumoniae capsular polysaccharide between elderly and young adults.
AB  - Streptococcus pneumoniae is one of the major causative agents of respiratory
      infections in the elderly population. The 23-valent pneumococcal polysaccharide
      vaccine is recommended for use in this age group. However, research has indicated
      that the protective efficacy of the vaccine declines with age. Although similar
      levels of antibody induction are seen in both young and elderly adults, following
      immunization with this vaccine, recent studies have indicated that the elderly
      possess antibodies with lower opsonophagocytic activity and avidity than young
      adults. We investigated whether a shift in V(H) gene usage may be responsible for
      this observation. To this end we utilized anti-idiotypic determinants to detect
      V(H)1 and V(H)3 gene usage by antibodies to pneumococcal capsular polysaccharides
      in both young and elderly subjects by enzyme-linked immunosorbent assay (ELISA).
      We found no significant difference in V(H)3 idiotypic expression in antibody
      responses to capsular polysaccharide from serotype 14 (PPS14). In response to
      PPS14 a significant higher level of V(H)1 idiotypic expressing antibodies was
      detected in the elderly as compared with young adults. V(H)1 idiotypic expression
      in response to capsular polysaccharide from serotype 4 (PPS4) was identical in
      young and elderly individuals. V(H)3 idiotypic expression in the elderly response
      to PPS4 was significantly lower than that seen in young individuals. These
      patterns of idiotypic expression are discussed in relation to recent studies of
      functional activity of pneumococcal reactive antibodies from young and aged
      humans.

PMID- 11991814
TI  - Identification of human mannose binding lectin (MBL) recognition sites for novel
      inhibitory antibodies.
AB  - Mannose binding lectin (MBL) binding initiates activation of the lectin
      complement pathway. Recent studies from our laboratory have demonstrated that MBL
      dependent complement activation mediates cellular injury following oxidative
      stress in vivo and in vitro. A panel of novel inhibitory monoclonal antibodies
      (MAbs) against MBL (e.g., MAb 3F8, 2A9, and hMBL1.2) has been developed that
      inhibit MBL binding and lectin pathway activation. Here, we further characterized
      the interactions of these MAbs and their Fab fragments to MBL. Whole MAbs or
      their Fab fragments bound to MBL with relatively high affinity. Fab fragments of
      3F8 were functionally effective in inhibiting MBL-dependent complement
      activation, however, steric hindrance of MAb 2A9 was essential for inhibition of
      MBL-dependent complement activation. We identified the hinge region, and residues
      EDCVLLL within the carbohydrate recognition domain of MBL as the recognition
      sites for MAb 3F8 and 2A9, respectively. The interaction of MAbs (e.g., 3F8 and
      2A9) to MBL was dependent on the conformation of their recognition sites. These
      findings demonstrate that MBL binding can be inhibited by at least two separate
      and independent mechanisms.

PMID- 11991815
TI  - Generation of monoclonal antibodies specific for desmoglein family members.
AB  - Desmosomes are the most prominent cell-cell junctions in most epithelial cells
      and serve to link the intermediate filament cytoskeletons of adjacent cells.
      Desmogleins and desmocollins are the transmembrane core of the desmosome and both
      are members of the cadherin family of cell-cell adhesion molecules. In the skin,
      the three desmoglein gene products (Dsg 1, 2, and 3) are expressed in a
      stratification dependent manner, and therefore contribute to compositionally
      different desmosomes throughout the differentiating layers. In this study we
      generated a panel of monoclonal antibodies (MAbs) specific for each of the
      desmoglein gene products and evaluated their usefulness in a number of
      immunological procedures including immunoblotting, immunoprecipitation, and
      immunofluorescence. In addition, we showed that these antibodies are useful for
      immunoprecipitating desmogleins from cell extracts prepared in 0.1% Empigen BB, a
      zwitterionic detergent capable of solubilizing the desmosomal structure.
      Identification of conditions that solubilize the desmosome and allow the use of
      immunological reagents will help facilitate an increased understanding of
      desmosome assembly and regulation.

PMID- 11991816
TI  - Immunogenic Cu2+-induced biopolymer systems comprising a steroid hormone, protein
      antigen, and synthetic polyelectrolytes.
AB  - We have synthesized the 17beta-estradiol comprising polycomplexes by the Cu(2+)
      mediated complex formation of polyanionic polyelectrolyte (PE), [polyacrylic acid
      (PAA), nontoxic copolymers (CP) of acrylic acid with N-isopropylacrylamide and N
      vinylpyrolidine] with BSA-estradiol covalent conjugates at the relatively low
      concentrations of metal ions in neutral water. Cu(2+) ions in the composition of
      biopolymer systems act as "fasteners" between macromolecules of same (negatively)
      charged polyanionic PE with protein carrier, promoting the formation of
      relatively stable polycomplex particles in physiological conditions. These hapten
      and protein comprising Biopolymer Systems possess simultaneously highly
      estradiol and BSA-specific immunogenicity without traditional adjuvants after a
      single intravenous immunization of mice. The obtained results are of interest for
      the construction of polydeterminant immunogen and vaccines based on polymer
      derivatives of steroid hormones.

PMID- 11991817
TI  - Monoclonal antibodies selective for low molecular weight neurofilaments.
AB  - Neurofilaments are necessary for the maintenance of axonal caliber and structural
      organization of nerve cells. The low molecular weight form of neurofilament, the
      neurofilament light protein, which serves as the core of the filament, was used
      as immunogen for generation of hybridomas with selective reactivity with this
      form of the filament. Six hybridomas, out of approximately 100 tested clones,
      were highly discriminatory. All involved epitopes were localized to the rod
      region of the antigen, as determined by alpha-chymotrypsin digestion of the
      purified filament and enzymatic peptide mapping. Synthetic peptides (20 mers)
      covering the entire rod region did not react with the antibodies. A phage display
      peptide library was used to identify four consensus sequences for the antibodies.
      The results indicate that all epitopes were of conformational type. Pair-wise
      BIAcore data furthermore indicated that the epitopes were independent. The access
      to such specific reagents is a prerequisite for further elucidation of the
      biology of the low molecular weight form of neurofilaments proteins.

PMID- 11991818
TI  - An antibody that binds to primary specific pocket-associated structure in the
      active site of bovine thrombin.
AB  - We attempted to produce a monoclonal antibody (MAb) against the active site of
      native thrombin. Bovine thrombin was treated with diisopropyl fluorophosphate,
      and prepared diisopropylphosphoryl-thrombin was used for the immunization to
      BALB/c mice. Spleen cells of immunized mice were hybridized with mouse myeloma
      cells P3U1, and a hybridoma clone CC2, which produced a MAb against bovine
      thrombin was established. The MAb produced by hybridoma clone CC2 (MAb(CC2)),
      consisting of IgG(1) and kappa light chain, was purified using protein A affinity
      chromatography. Purified MAb(CC2) prolonged the fibrin forming time of bovine
      thrombin and inhibited the release of fibrinopeptide A from rabbit fibrinogen. In
      addition, it was found that argatroban partially, but competitively, interfere
      the binding between MAb(CC2) and bovine thrombin. It was then considered that
      MAb(CC2) would bind to the molecular structure associating primary specific
      pocket in the active site of bovine thrombin.

PMID- 11991819
TI  - Monoclonal antibody-based enzyme immunoassay for detection of ricin.
AB  - A sensitive and specific enzyme-linked immunoadsorbent assay (ELISA) was
      developed to detect ricin in biological fluids. The assay is based on the
      sandwich format using monoclonal antibodies (MAbs) of two distinct specificities.
      An affinity-purified anti-ricin B chain MAb (1G7) is utilized to adsorb ricin
      from solution and the second anti-ricin A chain MAb (5E11) conjugated with
      peroxidase is then used to form a sandwich, and peroxidase allows color
      development and measurement of optical density at 450 nm. Standard curves were
      linear over the range of 2.5-100 ng/mL ricin. The limit of detection was below 5
      ng/mL in assay buffer as well as in a 1:10 dilution of urine or 1:50 dilution of
      human serum spiked with ricin.

PMID- 11991820
TI  - Characterization of novel anti-mouse thyrotropin monoclonal antibodies.
AB  - Mouse hybridoma cell lines have been raised to a peptide of the mouse thyrotropin
      beta (thyroid stimulating hormone [TSH]beta) subunit of the TSH glycoprotein
      hormone molecule. Using an enzyme-linked immunosorbent assay (ELISA) capture
      technique with two anti-TSHbeta monoclonal antibodies (MAbs), these reagents were
      found to have strong reactivity in a titration-dependent manner against normal
      mouse serum, and to precipitate under reducing conditions a 13-kDa product, the
      correct molecular size of the TSHbeta component, from mouse sera. These MAbs had
      minimal reactivity in ELISA to bovine and rat TSH and slight reactivity to human
      TSH, demonstrating overall strong species specificity for mouse TSH. Due to the
      large number of inbred and genetically manipulated mice now available for
      experimental research, it is anticipated that these reagents will be of
      considerable value for in-depth studies into TSH-related physiological processes
      in ways that have not been feasible here-to-fore.

PMID- 11991829
TI  - Establishing immunological tolerance through the induction of molecular
      chimerism.
AB  - One of the major goals of transplantation biology is to overcome transplant
      rejection without the need for life-long immunosuppression. Over the last several
      years, fundamental advances in our understanding of the immune response to
      allogeneic and xenogeneic antigens have stimulated a great deal of interest in
      the possibility of using gene therapy approaches to overcome the host response
      leading to transplant rejection while alleviating the need for non-specific
      immunosuppression. Here, we review recent progress in the field on the use of
      gene therapy to induce transplantation tolerance to donor organs and tissues.

PMID- 11991830
TI  - Targeting hepatic stellate cells for cell-specific treatment of liver fibrosis.
AB  - Since hepatic stellate cells (HSC) play a crucial role in the development of
      liver fibrosis, this cell is the major target for anti-fibrotic drugs. Most of
      the experimental drugs that influenced the HSC activity showed however low
      efficacy in vivo. Either a low uptake of the compounds in the cells that cause
      disease might account for this lack of effect, or side-effects in other cells may
      limit the dosage of the drugs. These side-effects may even counteract the
      beneficial effects. Therefore a selective delivery of drugs to the HSC may
      comprise a promising new way to improve liver fibrosis. The targeting to HSC has
      become a feasible option, because albumin-based carriers have been developed that
      preferentially distribute to HSC in fibrotic rat livers. In addition to the
      targeting of drugs, also the selective delivery of genes to HSC in fibrotic
      livers is of interest for therapeutic purposes and a start is made in this
      respect. The present review discusses the drugs to be targeted to HSC and
      summarizes some of the problems encountered during this novel strategy in the
      treatment of liver fibrosis.

PMID- 11991831
TI  - Adenovirus and cell cycle control.
AB  - Adenovirus infection of quiescent cells induces transition from G0 or G1 into the
      S phase of the cell cycle and allows cellular proliferation. This is beneficial
      for the virus since cells in S phase provide optimal conditions for viral
      replication. Adenovirus E1A, E1B and E4 gene products contribute to cell cycle
      deregulation. E1A proteins inactivate the pRb checkpoint, allowing the E2F
      transcription factor to activate genes involved in nucleotide metabolism and DNA
      replication, which are required in S phase. E1A also interacts with
      transcriptional modulators, including histone acetyltransferases, histone
      deacetylases, and other chromatin remodeling factors. These interactions affect
      transcription of several cellular and viral genes, some of which are involved in
      cell cycle regulation. Cell cycle deregulation by E1A results in stabilization
      and accumulation of p53. To prevent cell cycle arrest and apoptosis that would be
      triggered by p53, the adenovirus E1B and E4orf6 gene products employ various
      mechanisms to inactivate the tumor suppressor. Additional E4 gene products also
      interact with and modulate cell cycle regulators. Cell cycle checkpoints targeted
      by adenovirus proteins are often compromised in human tumors as well. Thus,
      understanding the interactions between adenovirus and the cell cycle has
      facilitated the generation of adenovirus mutants, which can replicate only in
      cells with inactivated checkpoints. Such "oncolytic" viruses are being tested for
      their ability to specifically replicate in and lyse cancer cells.

PMID- 11991832
TI  - Altered communication between L-type calcium channels and ryanodine receptors in
      heart failure.
AB  - Heart failure (HF) is a progressive syndrome that appears as the final phase of
      most cardiac diseases and is manifested as a decreased contractile function.
      Contraction in cardiomyocytes arises by the Ca2+ induced Ca2+ release mechanism,
      where Ca2+ entry (ICa) through Ca2+ channels (DHPRs) activates Ca2+ release
      channels (RyRs) in the junctional sarcoplasmic reticulum (SR). This is the base
      of cardiac excitation-contraction (EC) coupling. To elucidate the mechanisms
      underlying depressed function of the failing heart, analysis of EC coupling main
      elements have been undertaken. ICa density is usually maintained in HF. However,
      failing myocytes show a reduced SR Ca2+ release. Then, if the trigger of SR Ca2+
      release is maintained, why is SR Ca2+ release depressed in HF? Analyses of the
      DHPR-RyR coupling efficiency have revealed a decrease in the ICa efficacy to
      trigger Ca2+ release in failing myocytes. In terminal heart failure without
      hypertrophy, a decrease in SR Ca2+ load can account for the decreased SR Ca2+
      release. Fewer Ca2+ sparks (elementary units of SR Ca2+ release) are triggered by
      an equivalent ICa in hypertrophied failing myocytes, suggesting a functional or
      spatial reorganization of the space T-tubule junctional SR. This theory is
      supported by new data showing that the T-tubule density is reduced in failing
      cells.

PMID- 11991833
TI  - Mycoplasmosis and immunity of fish and reptiles.
AB  - Advances in molecular phylogenetics have enabled reconstruction of the most
      likely chronology of events in prokaryotic evolution and correlation with the
      paleontologic record with increasing precision. Mycoplasmas probably evolved from
      clostridial ancestors by genome reduction leading to obligate parasitism of host
      cells. The vertebrate hosts present at the time of the origin of mycoplasmas
      about 400 million years ago were fish, and later amphibians and reptiles, whose
      descendants possess most elements of vertebrate innate and adaptive immunity.
      Successful colonization of those poikilothermous ("cold-blooded") hosts must have
      involved adaptation to those defenses, shaping mycoplasma-host interactions for
      more than 125 million years before the earliest emergence of mammals. That
      history illuminates one aspect of the potential significance of mycoplasmosis of
      poikilothermous vertebrates to health and disease of other hosts including
      humans.

PMID- 11991834
TI  - Interferon-inducible p202 in the susceptibility to systemic lupus.
AB  - Systemic lupus erythematosus (SLE) is the prototype systemic autoimmune disease,
      which has potential to involve multiple organ systems. Studies in human SLE
      patients and murine models of lupus have indicated that genetic predisposition
      plays a crucial role in the development of this disease. To identify the genetic
      basis of human lupus and to understand the molecular mechanisms, mouse models of
      SLE have been studied. Generation of mice congenic for the Nba2 locus on the
      C57BL/6 genetic background, coupled with gene expression profiling, recently
      identified the interferon-activatable Ifi202 gene (encodes the protein p202) as a
      candidate lupus-susceptibility gene. The protein p202 is a member of the 200
      protein family. The family includes structurally and functionally related mouse
      and human interferon-inducible proteins. The protein p202 (52-kDa) is a
      relatively well-characterized phosphoprotein in the family with demonstrated
      ability to control cell-signaling pathways regulating cell proliferation,
      survival, and differentiation. Here, we review what is known about the gene
      Ifi202 and the protein it encodes. Moreover, we discuss how an understanding of
      the role of p202 in cell growth regulation, particularly in cells of the immune
      system, will help elucidate the molecular mechanisms contributing to the
      development of lupus.

PMID- 11991835
TI  - Role of innate immunity in respiratory mycoplasma infection.
AB  - Mycoplasmas are unique among respiratory pathogens. They possess very small
      genomes, lack cell walls and are strictly dependent on the host for survival.
      These pathogens have developed the ability to quickly adapt to the host
      environment through attachment to target cells within the host. Mycoplasmas have
      been identified as commensal microbial flora of healthy persons yet, infection of
      the upper and lower respiratory tracts can result in acute cough, fever and
      headache, and even chronic disease involving multiple organs. The lung contains a
      complex system of defense mechanisms with which to combat these pathogens,
      including innate (nonspecific) and acquired (specific) immune responses. Innate
      defenses include mechanical clearance, cellular responses provided by host
      phagocytes and molecular protection in the form of antimicrobial peptides. The
      interaction of mycoplasmas with different components of the innate immune system
      and mechanisms by which they incite pathology has proved elusive. The mechanisms
      by which pathogenic mycoplasmas evade the innate immune system are unknown. The
      purpose of this review is to summarize current knowledge of these interactions in
      the hope of identifying new avenues for research and therapy.

PMID- 11991836
TI  - Phagocytosis of apoptotic cells in mammals, caenorhabditis elegans and Drosophila
      melanogaster: molecular mechanisms and physiological consequences.
AB  - Phagocytosis is the necessary corollary of apoptosis. It leads to the clearance
      of apoptotic cells by phagocytes, which can be 'professional' or 'amateur'. I
      review the known molecular aspects of phagocytosis of apoptotic corpses in
      mammals, Caenorhabditis elegans and Drosophila melanogaster from the point of
      view of the phagocyte and the apoptotic corpse. I highlight recent advances made
      in the field and discuss the physiological outcomes and consequences of this
      process. Indeed, phagocytosis of apoptotic cells is important in shaping or
      remodeling tissues to maintain their integrity and specialized functions during
      development and wound healing. It also contributes to the development of
      inflammation and/or its resolution after an injury or infection. This perhaps
      explains why the molecular mechanisms of phagocytosis of apoptotic cells are
      redundant and complex in mammals and suggests why they appear to have been mostly
      conserved through evolution. Caenorhabditis elegans has already proven to be
      useful in genetically dissecting the molecular mechanisms underlying phagocytosis
      of apoptotic corpses by 'amateur' neighboring cells. Drosophila melanogaster will
      become the model of choice in genetically dissecting the molecular mechanisms
      underlying phagocytosis of apoptotic cells by 'professional' phagocytes such as
      macrophages.

PMID- 11991837
TI  - Signaling from cytokine receptors that affect TH1 responses
AB  - Receptors of the various cytokines although structurally diverse, can yet be
      grouped into four major families of receptor proteins. Most cytokines that
      function in the immune system bind to either the Class I or Class II receptor
      families. Two other important receptor families are the immunoglobulin
      superfamily receptor and the TNF receptor family. Members of these receptor
      families also have critical roles in the immune system. A common feature of all
      these receptor families is that they do not exhibit any intrinsic tyrosine kinase
      activity. Receptor signaling is initiated through recruitment of kinases and
      through recruitment of cytosolic proteins to the receptor. In this review we will
      examine receptor signaling pathways initiated from five receptors that are all
      involved in either initiating T helper-1 (Th1) responses, or in downregulating
      Th1 responses. The following receptors: Interleukin (IL)-12, Interferon (IFN), IL
      4, IL-10, and Tumor necrosis factor (TNF)-alpha will be examined. Signaling
      initiated from IL-12, IFN-gamma and TNF-alpha are important for inducing Th1
      responses, and on the other hand signaling from IL-4 and IL-10 receptors inhibit
      Th1 responses. We will also discuss human immunodeficiencies resulting from
      mutations in the genes that encode the Type I cytokine receptors.

PMID- 11991838
TI  - S100 proteins: structure, functions and pathology.
AB  - S100 proteins regulate intracellular processes such as cell growth and motility,
      cell cycle regulation, transcription and differentiation. Twenty members have
      been identified so far, and altogether, S100 proteins represent the largest
      subgroup in the EF-hand Ca2+ -binding protein family. A unique feature of these
      proteins is that individual members are localized in specific cellular
      compartments from which some are able to relocate upon Ca2+ activation,
      transducing the Ca2+ signal in a temporal and spacial manner by interacting with
      different targets specific for each S100 protein. Some members are even secreted
      from cells exerting extracellular, cytokine-like activities partially via the
      surface receptor RAGE (receptor for advanced glycation endproducts) with
      paracrine effects e.g. on neurons, promoting their survival during development or
      after injury. Another important aspect is that 14 bona fide S100 genes are found
      in a gene cluster on human chromosome 1q21 where a number of chromosomal
      abnormalities occur. This results in a deregulated expression of some S100 genes
      associated with neoplasias. Recently, S100 proteins have received increasing
      attention due to their close association with several human diseases including
      cardiomyopathy, neurodegenerative disorders and cancer. They have also been
      proven to be valuable in the diagnostic of these diseases, as predictive markers
      of improving clinical management, outcome and survival of patients and are
      considered having a potential as drug targets to improve therapies.

PMID- 11991839
TI  - Overcoming cardiac allograft vasculopathy (CAV) by inducing tolerance.
AB  - There is compelling evidence that MHC-driven immune processes play a dominant
      role in the development of cardiac allograft vasculopathy. Thus, it makes
      intuitive sense that tolerance, which eliminates donor alloreactivity, should
      protect against CAV. However, in the experimental literature, there are examples
      of CAV occurring in recipients rendered tolerant by either peripheral or central
      induction protocols. Why does transplant arteriopathy occur in recipients that
      have achieved a robust state of tolerance or in the animals devoid of T or B cell
      immunity? There may be immunological blindspots that persist even after a state
      of tolerance is achieved. These blindspots could contribute to the pathogenesis
      of chronic rejection (CR).

PMID- 11991840
TI  - The role of the graft in establishing tolerance.
AB  - At the present time, clinical solid organ transplantation continues to rely on
      the use of non-specific immunosuppressive protocols in order to prevent graft
      rejection. However, these regimens bring with them complications related both to
      the global immunosuppression that they cause, and to toxicity related to
      individual drugs. The pursuit of protocols that will allow graft-specific
      tolerance thus remains a major goal of research both in animal models and in
      clinical practice. There is evidence that the graft itself may play an active
      part in establishing and maintaining donor-specific hyporesponsiveness and
      ultimately tolerance; the aim of this review is to analyze this role in more
      detail.

PMID- 11991841
TI  - Xenotransplantation and tolerance.
AB  - Donor organ availability has become a major limiting factor in the progress of
      allotransplantation. This, and advances in genetic engineering in pigs, have led
      to increasing interest in the use of xenogeneic organs. In view of the greater
      difficulty encountered in overcoming immune responses to xenografts than to
      allografts, the success of clinical xenotransplantation may depend on finding
      ways of inducing specific hyporesponsiveness, or tolerance, across xenogeneic
      barriers rather than by relying on nonspecific immunosuppressive agents. This
      review discusses the barriers to xenogeneic organ transplantation and the
      approaches that are being developed to overcome them, with the emphasis on
      methods that attempt to induce tolerance.

PMID- 11991842
TI  - Statistical methods for analysis of time course gene expression data.
AB  - Since many biological systems or regulatory networks are dynamic systems, gene
      expression levels measured over different time points during a given biological
      process can often provide more insights about the underlying system. These gene
      expression data measured over time are often called the time-course gene
      expression data. One unique feature of such data is the time dependency of the
      gene expression levels for a given gene at different times or between two
      different genes. Statistical analysis needs to account for such dependency in
      order to make valid inferences. This paper presents several statistical methods
      for analyzing such time-course gene expression data, including the time-lagged
      correlation coefficient for analyzing the relationship between genes, a mixed
      effects model with splines for clustering genes and for estimating missing gene
      expression data, and a new method for aligning gene expression profiles obtained
      under two experimental conditions and for identifying gene clusters that show
      significant changes between two experimental conditions. We used the yeast cell
      cycle gene expression data sets to illustrate these methods and obtained the
      biologically meaningful conclusions from these analyses.

PMID- 11991843
TI  - Kaposi's sarcoma associated herpesvirus immune evasion strategies.
AB  - The battle between viruses and their hosts is beautiful in its complexity. The
      interplay between viral proteins and the immune system has taught researchers
      much about not just the virus, but also the molecular mechanisms underlying the
      immune response. With additional evasion strategies constantly being described,
      this avenue of research is still rich with potential discoveries. In this review,
      we examine a number of proteins encoded by Kaposi's sarcoma herpesvirus (HHV-8)
      and detail how they aid the virus in escape from immune system elimination. We
      include, where possible, examples from other homologous viral systems.

PMID- 11991844
TI  - Calcium quarks.
AB  - Elementary subcellular Ca2+ signals arising from the opening of single ion
      channels may offer the possibility to examine the stochastic behavior and the
      microscopic chemical reaction rates of these channel proteins in their natural
      environment. Such an analysis can yield detailed information about the molecular
      function that cannot be derived from recordings obtained from an ensemble of
      channels. In this review, we summarize experimental evidence suggesting that Ca2+
      sparks, elementary Ca2+ signaling events of cardiac and skeletal muscle
      excitation contraction coupling, may be comprised of a number of smaller Ca2+
      signaling events, the Ca2+ quarks.

PMID- 11991845
TI  - Ryanodine receptor isoforms of non-Mammalian skeletal muscle.
AB  - Whereas mammalian skeletal muscles express primarily a single isoform of
      ryanodine receptor (RyR) as the Ca2+ releasing channel, many non-mammalian
      vertebrate skeletal muscles express two isoforms in almost similar amount, alpha-
      and beta-RyR which are homologues of mammalian isoforms RyR1 and 3, respectively.
      alpha-RyR is believed to be directly involved in excitation-contraction coupling
      in skeletal muscles and is variable in its properties among animals and fibers,
      while beta-RyR shows similar properties and is variable in its content. alpha-
      and beta-RyR purified from frog skeletal muscle, a favorite material for
      physiological and morphological experiments, are very similar in Ca2+ dependent
      [3H]ryanodine binding. On the SR membrane, however, alpha-RyR is selectively
      suppressed in the ligand binding, indicating that the Ca2+-induced Ca2+ release
      (CICR) activity in skeletal muscle is conducted primarily by beta-RyR. We also
      stressed here that Ca2+ binding to the activating site is a necessary but not a
      sufficient condition for CICR. The maximum activity attainable under a specified
      condition is also a critical parameter to be determined. Taking these findings
      into consideration, we conclude that CICR is too slow to explain the
      physiological Ca2+ release on depolarization.

PMID- 11991846
TI  - T cells and aging, January 2002 update.
AB  - Age-related changes in the immune system may contribute to morbidity and
      mortality due to decreased resistance to infection and, possibly, certain cancers
      in the aged. Many studies mostly performed in mice, rats and man but also
      including monkeys and dogs have established that age-associated immune decline is
      characterized by decreases in both humoral and cellular responses. The former may
      be largely a result of the latter, because observed changes both in the B cell
      germline-encoded repertoire and the age-associated decrease in somatic
      hypermutation of the B cell antigen receptors are now known to be critically
      affected by helper T cell aging. As antigen presenting cell (APC) function
      appears to be well-maintained in the elderly, this review will focus on the T
      cell. Factors contributing to T cell immunosenescence may include a) altered
      production of T cell progenitors (stem cell defects, stromal cell defects), b)
      decreased levels of newly-generated mature T cells (thymic involution), c) aging
      of resting immune cells, d) disrupted activation pathways in immune cells
      (stimulation via the T cell receptor for antigen, costimulation, apoptosis
      control), e) replicative senescence of clonally expanding cells. This review aims
      to consider the current state of knowledge on the scientific basis for and
      potential clinical relevance of those factors in immunosenescence in humans.
      Experiments in other species will be touched upon with the proviso that there are
      clearly differences between them, especially between humans and rodents, but
      exactly what those differences are is not completely clear. Given its potential
      importance and the increasing proportion of elderly people the world over,
      coupled with the realisation that whereas mortality is decreasing, morbidity may
      not be decreasing in parallel (1), a better understanding of the causes and
      impact of immunosenescence may offer the possibility of identifying where
      prevention or delay of onset, as well as therapeutic intervention, might be
      beneficial. Amelioration of the effects of dysregulated immune responses in the
      elderly by replacement therapy, supplementation therapy or other approaches may
      result in an enhancement of their quality of life, and significant reductions in
      the cost of medical care in old age.

PMID- 11991847
TI  - Decreased mitochondrial carnitine translocase in skeletal muscles impairs
      utilization of fatty acids in insulin-resistant patients.
AB  - Insulin resistance (IR) and its health consequences (diabetes, hypertension,
      cardiovascular disease, obesity etc.) affect between 25 and 35% of Westernized
      populations. Decreased fatty acid (FA) oxidation in skeletal muscle is implicated
      in obesity-related IR. Carnitine-acylcarnitine translocase (CACT) transports long
      chain FAs both into mitochondria (as carnitine esters for energy-generating
      processes) and out of mitochondria. To determine whether CACT activity correlates
      with decreased FA oxidation we measured CACT concentrations in cellular and
      mitochondrial extracts from the skeletal muscle of 19 obese IR individuals and of
      19 lean controls. We also evaluated carnitine transport in skeletal muscle
      mitochondria in both groups. Mitochondrial CACT was decreased at translational
      and transductional level, and carnitine-carnitine and acylcarnitine-carnitine
      exchange rates were significantly lower in IR subjects. Aberrant acylcarnitine
      flux into mitochondria was not correlated with decreased activity of other
      components of the mitochondrial carnitine system (i.e., carnitine palmitoyl
      transferase-I and II). Our data suggest that by restraining entry of FA-coenzyme
      A into mitochondria, low CACT levels increase cytosolic FA levels and their
      incorporation into glycerolipids. The low level of CACT in IR muscle may
      contribute to the elevated muscle concentrations of triglycerides,
      diacylglycerol, and FA-coenzyme A characteristic of IR muscle.

PMID- 11991848
TI  - Redox sensing properties of the ryanodine receptor complex.
AB  - The release mechanism regulating SR Ca2+ homeostasis is significantly more
      sensitive than the uptake mechanisms. The exquisite sensitivity exhibited by
      ryanodine-sensitive Ca2+ channel complexes (i.e., ryanodine receptors, RyRs) to
      functional perturbation by chemically diverse sulfhydryl-modifying compounds can
      include phases of activation and inhibition that are dependent on the
      concentration of the reagent used, the length of exposure, and the nature of the
      chemical reaction the reagent undertakes with sulfhydryl groups. However the
      exquisite sensitivity of RyR function to sulfhydryl modification has been
      generally viewed as significant only in pathophysiological processes. The present
      paper addresses possible physiological importance of the redox sensing properties
      of the ryanodine receptor complexes (RyRs) and proposes an underlying mechanism.
      New data is presented that directly measure the pKa of hyperreactive thiols that
      occur when the closed conformation of the RyR channel complex is assumed, and
      that appear to be an integral component of the redox sensor.

PMID- 11991849
TI  - Targeting Kupffer cells with antisense oligonucleotides.
AB  - During proinflammatory reactions such as endotoxemia, ischemia-reperfusion and
      immune reactions, excessive amounts of cytokines and prostanoids are released
      resulting in liver injury. In the liver, Kupffer cells are the primary source of
      cytokines and prostanoids. Obliteration of Kupffer cells prevents experimentally
      induced liver damage, suggesting a major role for Kupffer in the pathogenesis of
      liver diseases. Pretreatment of experimental animals with antibodies directed
      against cytokines such as tumor necrosis alpha (TNF-alpha) prevented
      experimentally-induced liver damage. In recent years, antisense oligonucleotides
      (ASOs) directed against specific mRNAs have been tested as an alternative therapy
      to control the excessive production of inflammatory peptides. Although ASOs have
      great potential against gene expression, their design, in vivo delivery and
      stability, have posed significant challenges. Computer-aided configurational
      analysis and identification of viable motifs (GGGA) on the pre-mRNA transcripts
      have, in part, alleviated the problems in designing effective ASOs. However, the
      major challenge involves the in vivo delivery of an ASO to the target tissue.
      Additionally, it is critical that once taken up by the cells, the ASO is able to
      survive the lysosomal barrier and enter the cytoplasm. Anionic liposomes and
      lactosylated low-density lipoproteins (LDL) have been successively used as
      adjuvants for delivery of ASOs to Kupffer cells. In particular, pH-sensitive
      liposomes have shown great promise as delivering vehicles to target Kupffer
      cells. In summary, although ASOs are emerging as a new class of drugs against
      Kupffer cell-derived pro-inflammatory molecules, in vivo delivery still remains a
      challenge. pH-sensitive liposomes and LDL-based delivery systems show significant
      promise for specifically targeting Kupffer cells.

PMID- 11991850
TI  - Molecular regulation of iron homeostasis and resistance to infection in
      alcoholics.
AB  - Chronic alcohol abuse is associated with both an altered response to infection
      and deranged iron homeostasis. While both clinical manifestations are well known,
      the inter-relationships between alcohol and iron and the response to infection
      are not. The recent identification of a plethora of iron regulatory and transport
      proteins has now begun to explain these relationships. This article outlines the
      current state of knowledge on cellular iron homeostasis, with particular
      reference to the iron regulatory proteins (IRP1, IRP2 and HFE) and the iron
      membrane transport proteins, two of which have been shown to be members of the
      natural resistance- associated macrophage protein family (Nramp1 and 2).
      Following this introduction, the response of the body to infection, in terms of
      iron withholding is discussed at the cellular level, especially in terms of the
      macrophage and its cytokine-mediated responses. Prior alterations to body iron
      status are also considered in this section. The effect of alcohol alone on the
      body's response to infection is then outlined, principally in terms of the
      macrophage function and cytokine regulation. These are then combined to correlate
      the clinical and experimental observations with known derangements produced by
      the individual insults of alcohol and altered iron homeostasis. on the response
      to infection. Particular attention is paid not only to cytokine/chemokine
      actions, but also to the consequences of the altered production of reactive
      oxygen and nitrogen species. Finally, the possible mechanisms by which alcohol
      and altered iron homeostasis lead to tissue damage during infection.

PMID- 11991851
TI  - Alcohol-induced alterations in serum immunoglobulin e (IgE) levels in human
      subjects.
AB  - The association of alcohol intake with total serum IgE concentrations in humans
      is discussed in the present review. The possible relationship of regular alcohol
      intake with both the risk of allergic sensitization and serum allergen-specific
      IgE values is also reviewed. Several studies consistently show that total serum
      IgE concentrations are increased in alcoholics when compared with healthy
      controls. Total serum IgE levels decrease after ethanol abstinence in alcoholics.
      Total serum IgE is increased in moderate alcohol consumers with respect to
      abstainers. Alcohol consumption in mothers may be associated with increased cord
      blood IgE levels in their offspring. IgE elevation in alcohol consumers is
      independent of potential confounders such as age, sex, liver disease, cigarette
      smoking or atopic status. Experimental studies in animals further support that
      ethanol administration is followed by an increase in serum IgE concentrations. In
      atopic patients, regular alcohol consumption is associated with increased serum
      specific IgE levels against some aeroallergens. Preliminary reports suggest that
      alcohol intake is associated to variable risk of sensitization to some
      aeroallergens. The possible mechanisms of alcohol-induced alterations in IgE
      levels and IgE-mediated diseases are discussed.

PMID- 11991852
TI  - Initiation and termination of calcium sparks in skeletal muscle
AB  - Three main paths to derive the Ca2+ release flux underlying Ca2+ sparks are
      reviewed here: Some properties of release flux can be inferred from an
      examination of spark morphology. Others from model simulations, which generate
      sparks assuming an ion source within a cytoplasm-like medium. Finally, the
      release flux can be derived from the fluorescence transient by generalizing an
      algorithm developed earlier for global or whole cell signals. The transient and
      spatially limited nature of sparks adds many uncertainties to the process. These
      methods yield estimates between 1.4 and 30 pA, not clearly greater in skeletal
      than in cardiac muscle. At their low end, the estimates are consistent with
      generation of sparks by one or two ryanodine receptor channels, but the results
      are easier to explain if several channels, from as little as four to as many as
      60, cooperate in their generation. How release flux determines spark shape and
      time course has been understood largely through simulations. The rise time of
      sparks corresponds to active release time. Both release flux and release time may
      vary among individual sparks, leading to their varied size and shape. Release
      flux turns off abruptly, therefore the decay of sparks is determined by Ca2+
      removal and diffusion. Spatial width increases with release time (rise time).
      That its experimentally determined value is too large compared with simulations,
      remains the single most important question in the interpretation of shape. Sparks
      are not the sole form of local fluorescence transients. When channel opening
      drugs are present, or sometimes spontaneously, sparks may be prolonged by embers.
      If the release flux calculated during an ember corresponds to a single open
      channel, then the release underlying a spark must require many open channels. The
      continued examination of Ca2+ release flux appears to be an essential requisite
      for the interpretation of sparks and their place in calcium signaling.

PMID- 11991853
TI  - Ins and outs of clinical trials with peptide-based vaccines.
AB  - Peptides are the smallest antigenic components that are recognized by T cells
      when presented in MHC molecules on the cell surface. After the identification of
      peptides from tumor associated and tumor specific antigens, the exploration of
      the use of peptides in immunotherapy of cancer was instigated. From initial
      exploration of peptide-mediated induction of immune responses in mice, the
      peptide based vaccines have evolved to clinical testing in cancer patients. Many
      different clinical trials have been performed to address the ability of peptide
      based vaccines to induce both clinical and immunological responses in patients.
      This review will provide an overview of the results of the majority of the
      clinical trials with peptide-based vaccines directed against various antigens in
      patients with solid tumors.

PMID- 11991854
TI  - Initiation and termination of calcium sparks in skeletal muscle.
AB  - Depolarization of the transverse tubules of a skeletal muscle fiber initiates
      release of Ca2+ ions via ryanodine receptor (RyR) Ca2+ release channels in the
      adjacent junctional sarcoplasmic reticulum (SR) membrane at triad junctions.
      Discrete localized Ca2+ release events (Ca2+ "sparks") detected by confocal
      imaging of Ca2+ indicator-containing muscle fibers may arise from the coordinated
      opening of a small group of RyR Ca2+ release channels, or possibly even from the
      opening of a single channel. These discrete Ca2+ release events originate at
      triad junctions and can be gated by fiber depolarization or by physiological
      cytosolic ligands (e.g., Ca2+ and Mg2+) in functioning muscle fibers. The global
      increase in myoplasmic Ca2+ during fiber depolarization appears to consist of the
      summation of huge numbers of Ca2+ sparks initiated during a brief time interval.
      Study of Ca2+ sparks thus offers a unique window into the operation of groups of
      SR Ca2+ release channels or individual channels within the normal structural and
      molecular environment of a functioning fiber. The Ca2+ release underlying a spark
      appears to turn on and off abruptly respectively at the start and at the peak of
      a spark. Under many stimuli, the frequency and/or pattern of occurrence of the
      Ca2+ sparks is altered, indicating changes in the closed time (or opening rate)
      of the channels that initiate the sparks. In contrast, the average values of the
      spatio-temporal properties of the individual events generally remain unchanged,
      indicating constancy of channel open time and constancy of total Ca2+ efflux via
      the channels generating a spark. A few conditions that alter the average
      properties of Ca2+ sparks provide rare insights regarding the open-time of the
      Ca2+ channels generating the Ca2+ spark.

PMID- 11991855
TI  - Patterns of cognitive impairment in Alzheimer's disease: assessment and
      differential diagnosis.
AB  - In routine clinical practice, the diagnosis of Alzheimer's disease (AD) is
      commonly made according to NINCDS-ADRDA criteria. As pathological verification is
      typically not available, such a diagnosis remains probable rather than definite.
      A diagnosis of probable AD is nevertheless fairly accurate (0.75-0.96), and may
      serve as a surrogate gold standard in clinical studies. Probable AD is often
      considered a diagnosis of exclusion, but AD neuropathology characteristically
      evolves in an ordered topographic sequence, which is mirrored in the pattern of
      evolution of neuropsychological deficits. Recognition of the resulting temporal
      profile of cognitive domain involvement allows positive rather than merely
      exclusionary diagnosis. Certain other dementias may be difficult to distinguish
      from AD clinically: notably frontotemporal dementia (FTD), dementia with Lewy
      bodies (DLB), and various subtypes of vascular cognitive impairment. The
      distinction is made more difficult by the existence of variants of AD, presenting
      with predominant impairment of executive, visuoperceptual, or language domains,
      as well as by the common occurrence of mixed pathologies. Against this
      background, the neuropsychological features of AD and its variant presentations,
      and its distinction from other dementias are reviewed. The properties of commonly
      used cognitive assessment tools (MMSE, Mattis DRS, ADAS-Cog, CERAD and CAMDEX-R)
      are discussed, and the issue of diagnosing incipient AD on clinical grounds
      before the NINCDS-ADRDA criteria are fulfilled is addressed.

PMID- 11991856
TI  - Ethanol-mediated regulation of transcription factors in immunocompetent cells.
AB  - The immunomodulatory effects of acute and chronic alcohol use are characterized
      by impaired antigen-specific immune activation and by increased susceptibility to
      infections due to alterations in innate immune responses and inflammatory
      mediator production. The central feature of cellular responses to inflammatory
      and stress signals is the activation of the nuclear regulatory kappa B/Rel family
      of transcriptional factors via various surface receptor systems in
      immunocompetent cells. Activation of NF-kappa B, however, is regulated at
      multiple levels including I-kappa B degradation, nuclear translocation, and by
      interaction of NF-kappa B/Rel with other transcription factors. Data from our and
      other laboratories demonstrate that acute alcohol treatment inhibits activation
      and nuclear binding of the p65/p50 NF-kappa B functional heterodimer in human
      monocytes, a mechanism likely contributing to inhibition of pro-inflammatory
      cytokine production. Here we show that acute alcohol-mediated inhibition of NF
      kappa B activation in various monocytic cells including human monocytes and
      murine macrophages. Inhibition of NF-kappa B activation by alcohol in monocytic
      cells was independent of I-kappa B alpha degradation. These acute-alcohol-induced
      changes in monocytic cells were different compared to T lymphocytes, both in
      Jurkat CD4 cells and peripheral human T cells, acute alcohol had a biphasic
      effect on TNF-alpha-induced NF-kappa B activation via an I-kappa B alpha
      dependent mechanism. Inhibition of NF-kappa B activation by acute alcohol in LPS
      activated human monocytes was associated with an increase in nuclear
      glucocorticoid receptor (GR) levels and reduced GR binding to the glucocorticoid
      response element (GRE). Together these findings support the hypothesis that in
      the presence of alcohol, nuclear interaction of NF-kappa B (p65) with
      glucocorticoid receptor and/or other transcription factors may contribute to the
      reduced NF-kappa B activation. In contrast to the inhibitory effects of acute
      alcohol on NF-kappa B activation in monocytic cells, chronic alcohol use and
      alcoholic hepatitis result in an augmentation of NF-kappa B activation and pro
      inflammatory cytokine induction. These results suggest that the complex
      interactions of the NF-kappa B/Rel and related transcription factors including GR
      and heat-shock responses determine the level of activation of the immunocompetent
      cells in response to the challenge of acute and chronic alcohol use at the single
      cell level.

PMID- 11991857
TI  - Homeostasis of extracellular matrix by TGF-beta and lefty.
AB  - Both normal and neoplastic tissues have a stroma comprised of fibroblasts which
      deposit an extracellular matrix (ECM) enriched in collagen. In most normal
      tissues, the synthesis and breakdown of the ECM is maintained at a low level.
      However, in normal adult tissues such as endometrium, and in rapidly growing
      embryonic and neoplastic tissues, there is a significant increase in the
      synthesis and/or breakdown of ECM. The homeostasis of the ECM is maintained by a
      molecular repertoire which appears to consist of TGF-beta and lefty. TGF-beta
      acts as a pro-fibrogenic cytokine by increasing the synthesis of collagen and
      decreasing the degradation of ECM. Physiologic levels of TGF-beta maintains
      tissue homeostasis and aberrant over-expression of TGF-beta leads to tissue
      fibrosis. TGF-beta acts through a core Smad signaling pathway which is initiated
      by the binding of homo-dimeric TGF-beta protein to two type I and II receptors.
      The constitutively active receptor type II leads to phosphorylation of receptor
      type I which, in turn, causes the R-Smads to get phosphorylated. The downstream
      gene transcriptional activity of this event includes significant increase in
      connective tissue growth factor (CTGF) and collagen mRNA synthesis which leads to
      deposition of collagen in tissues. Lefty inhibits Smad2 phosphorylation initiated
      by TGF-beta or its receptor and prevents CTGF promoter activity driven by TGF
      beta. Moreover, lefty inhibits CTGF and collagen mRNA synthesis and increases
      collagenolysis and elastolysis and as a result of these actions, lefty
      significantly reduces the amount of collagen deposited in tissues. Thus, TGF-beta
      and lefty might coordinately participate in the homeostasis of ECM in tissues.

PMID- 11991858
TI  - Modulating Ca2+ clearance from neurons.
AB  - Neurons are exquisitely sensitive to the duration, amplitude and localization of
      transient increases in intracellular Ca2+ concentration ([Ca2+]i). Modulation of
      Ca2+ uptake into the mitochondrion and endoplasmic reticulum, and efflux via the
      plasma membrane Ca2+ pump and Na+/Ca2+ exchange profoundly affect the shape of
      [Ca2+]i signals. Ca2+ clearance mechanisms are modulated by other signaling
      pathways, are sensitive to metabolic state and have a memory of the recent
      history of cell activation. We present here examples of pharmacologic and
      endogenous regulation of Ca2+ sequestration and efflux in neurons. Ca2+ clearance
      mechanisms differentially shape [Ca2+]i signals based on their affinity, capacity
      and location; their modulation alters specific neuronal functions. The
      increasingly apparent diversity of the molecular entities that make up the
      [Ca2+]i regulatory system reveals new sites for modulation. Specialized Ca2+
      clearance mechanisms participate in unique cellular functions and thus, are
      important targets for pharmacological and physiological regulation of the neuron.

PMID- 11991859
TI  - Biological role of phosphatase PTEN in cancer and tissue injury healing.
AB  - PTEN (phosphatase and tensin homolog deleted on chromosome ten) also referred to
      as MMAC (mutated in multiple advanced cancers) was discovered as a tumor
      suppressor gene and later found to be a phospholipid phosphatase. PTEN negatively
      regulates Akt activation by preventing its phosphorylation. PTEN therefore
      inhibits the PI 3-kinase/Akt signaling pathway which is important for cell growth
      and survival. Overexpression or enhanced activation of PTEN can potentially
      impair injury healing by at least 4 mechanisms. PTEN can: 1) inhibit entry into
      the cell cycle by inhibiting G1 to S phase progression and arrest cell
      proliferation required for tissue reconstruction during injury healing; 2)
      increase apoptosis by blocking Akt activation leading to increased Bad and
      Caspase-9 activities; 3) inhibit hypoxia-induced angiogenesis required for injury
      healing by blocking Akt-mediated VEGF gene transcription; 4) inhibit Akt-mediated
      cell migration, i.e. re-epithelialization, which is also required for injury
      healing. The same mechanisms can also suppress cancer growth and metastases.
      Therefore, elucidating the role of the PTEN/PI 3-kinase/Akt pathway will likely
      advance our knowledge of the mechanisms controlling the processes of injury
      healing and cancer growth.

PMID- 11991860
TI  - Ion conduction and selectivity in the ryanodine receptor channel.
AB  - The ryanodine receptor channel is an intracellular membrane Ca2+-release channel.
      The investigation of ion translocation and discrimination in individual channels
      under voltage-clamp conditions has revealed that the channel can sustain very
      high rates of cation translocation, has high affinity for divalent cations and
      displays relatively poor discrimination between physiologically relevant cations.
      In this article I will discuss the mechanisms underlying these characteristic
      properties, the regions of the channel molecule likely to be involved in ion
      handling and speculate on the structure of the conduction pathway of Ca2+-release
      channels.

PMID- 11991861
TI  - Tree-based analysis of microarray data for classifying breast cancer.
AB  - DNA microarray data have provided us with the opportunity to assess the
      expression levels for thousands of genes simultaneously. One of the uses of this
      information is to classify cancer tumors. A noted challenge in using microarray
      information is analytical. Following the work of Zhang et al. (1), we further
      pursue the use of recursive partitioning in analyses of microarray data for
      cancer classification. Not only does the recursive partitioning technique create
      intuitive classification rules, but also it is most flexible as to the handling
      of a massive number of genes, missing expressions, and multi-class tissues. Using
      a published data set (2), we demonstrate that the recursive partitioning
      technique creates a more precise and simpler classification rule than other
      commonly used approaches. In particular, we introduce the concept of A-tree and
      propose a procedure to assess a large number of A-trees. One of the identified
      genes (ERBB2) is in the close region of BRCA1 (17q21.1) and has been shown by
      others to have altered expression levels in breast cancer. Nonetheless, our
      identified genes warrant further investigation as to whether they play a role in
      the etiology of breast cancer.

PMID- 11991862
TI  - Pulmonary host defenses and alcohol.
AB  - Alcohol abuse is a major risk factor for the development of many infectious
      diseases, particularly pulmonary infections. Bacterial pneumonia and other lung
      infections in alcohol-abusing patients are usually severe and associated with a
      high morbidity and mortality. Normal host defense mechanisms in the respiratory
      tract consist of both innate and acquired immunity which operate effectively in
      preventing the invasion of infectious pathogens. Numerous in vivo and in vitro
      studies have shown that alcohol is an immunosuppressive agent that compromises
      the function of various components of the immune defense system. In recent years,
      human immunodeficiency virus infection has become epidemic, especially in
      individuals who abuse alcohol and other substances. Treatment of pulmonary
      infections in these immunocompromised hosts has continued to be a major challenge
      in our health care system. Immunotherapy to improve or enhance pulmonary host
      defense function in conjunction with aggressive antimicrobial regimens may
      provide a new approach in the management of infections in these patients.

PMID- 11991863
TI  - Genetic basis of familial interstitial lung disease: misfolding or function of
      surfactant protein C?

PMID- 11991864
TI  - Manual aspiration: the preferred method for managing primary spontaneous
      pneumothorax?

PMID- 11991865
TI  - Crossing the threshold: implications for central sleep apnea.

PMID- 11991866
TI  - Pro: Inflammatory mechanisms are a minor component of the pathogenesis of
      idiopathic pulmonary fibrosis.

PMID- 11991867
TI  - Con: Inflammatory mechanisms are not a minor component of the pathogenesis of
      idiopathic pulmonary fibrosis.

PMID- 11991870
TI  - New treatments for pulmonary arterial hypertension.

PMID- 11991871
TI  - Epidemiology of obstructive sleep apnea: a population health perspective.
AB  - Population-based epidemiologic studies have uncovered the high prevalence and
      wide severity spectrum of undiagnosed obstructive sleep apnea, and have
      consistently found that even mild obstructive sleep apnea is associated with
      significant morbidity. Evidence from methodologically strong cohort studies
      indicates that undiagnosed obstructive sleep apnea, with or without symptoms, is
      independently associated with increased likelihood of hypertension,
      cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and
      diminished quality of life. Strategies to decrease the high prevalence and
      associated morbidity of obstructive sleep apnea are critically needed. The
      reduction or elimination of risk factors through public health initiatives with
      clinical support holds promise. Potentially modifiable risk factors considered in
      this review include overweight and obesity, alcohol, smoking, nasal congestion,
      and estrogen depletion in menopause. Data suggest that obstructive sleep apnea is
      associated with all these factors, but at present the only intervention strategy
      supported with adequate evidence is weight loss. A focus on weight control is
      especially important given the expanding epidemic of overweight and obesity in
      the United States. Primary care providers will be central to clinical approaches
      for addressing the burden and the development of cost-effective case-finding
      strategies and feasible treatment for mild obstructive sleep apnea warrants high
      priority.

PMID- 11991872
TI  - Manual aspiration versus chest tube drainage in first episodes of primary
      spontaneous pneumothorax: a multicenter, prospective, randomized pilot study.
AB  - Although there is no agreement on the optimal treatment of patients presenting
      with a first episode of primary spontaneous pneumothorax, the majority of
      physicians prefer chest tube drainage for air evacuation. Manual aspiration of
      air has been proposed by some, but lack of sound comparative data and safety data
      has limited its use. In this first randomized, prospective, multicenter pilot
      study, 60 patients with a first episode of primary spontaneous pneumothorax were
      randomly allocated to manual aspiration (n = 27) or chest tube drainage (n = 33).
      Immediate success was obtained in 16 out of 27 (59.3%) in the manual aspiration
      group, and in 21 out of 33 (63.6%) in the chest tube drainage group (p = 0.9).
      One-week success rates were 25 out of 27 (93%) in the intention-to-treat manual
      aspiration group and 28 out of 33 (85%) in the chest tube drainage group (p =
      0.4). Fourteen of 27 manual aspiration patients (52%) were hospitalized, versus
      100% of the chest tube drainage patients (p < 0.0001). Recurrence rates with at
      least 1-year follow-up were 7 out of 26 (26%) in the manual aspiration group, and
      9 out of 33 (27.3%) in the chest tube drainage group (p = 0.9). There were no
      complications associated with manual aspiration. Although statistical power is
      insufficient to formally confirm therapeutic equality, this pilot study suggests
      that in first episodes of primary spontaneous pneumothorax, manual aspiration
      seems equally effective as chest tube drainage and is safe, well tolerated, and
      feasible as an outpatient procedure in the majority of patients.

PMID- 11991873
TI  - Apnea-hypopnea threshold for CO2 in patients with congestive heart failure.
AB  - To understand the pathogenesis of central sleep apnea (CSA) in patients with
      congestive heart failure (CHF), we measured the end-tidal carbon dioxide pressure
      (PET(CO2)) during spontaneous breathing, the apnea-hypopnea threshold for CO2,
      and then calculated the difference between these two measurements in 19 stable
      patients with CHF with (12 patients) or without (7 patients) CSA during non-rapid
      eye movement sleep. Pressure support ventilation was used to reduce the PET(CO2)
      and thereby determine the thresholds. In patients with CSA, 1.5-3% CO2 was
      supplied temporarily to stabilize breathing before determining the thresholds.
      Unlike patients without CSA whose eupneic PET(CO2) increased during sleep (37.7
      +/- 1.4 mm Hg versus 40.2 +/- 1.5 mm Hg, p < 0.01), patients with CSA showed no
      rise in PET(CO2) from wakefulness to sleep (37.5 +/- 0.9 mm Hg versus 38.2 +/-
      1.0 mm Hg, p = 0.2). Patients with CHF and CSA had their eupneic PET(CO2) closer
      to the threshold PET(CO2) than patients without CSA (DeltaPET(CO2) [eupneic
      PET(CO2) - threshold PET(CO2)] was 2.8 +/- 0.3 mm Hg versus 5.1 +/- 0.7 mm Hg for
      apnea, p < 0.01; 1.7 +/- 0.7 versus 4.1 +/- 0.5 mm Hg for hypopnea, p < 0.05). In
      summary, patients with CHF and CSA neither increase their eupneic PET(CO2) during
      sleep nor proportionally decrease their apnea-hypopnea threshold. The resultant
      narrowed DeltaPET(CO2) predisposes the patient to the development of apnea and
      subsequent breathing instability.

PMID- 11991874
TI  - Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during
      sleep.
AB  - We determined the effects of changing ventilatory stimuli on the hypocapnia
      induced apneic and hypopneic thresholds in sleeping dogs. End-tidal carbon
      dioxide pressure (PET(CO2)) was gradually reduced during non-rapid eye movement
      sleep by increasing tidal volume with pressure support mechanical ventilation,
      causing a reduction in diaphragm electromyogram amplitude until apnea/periodic
      breathing occurred. We used the reduction in PET(CO2) below spontaneous breathing
      required to produce apnea (DeltaPET(CO2)) as an index of the susceptibility to
      apnea. DeltaPET(CO2) was -5 mm Hg in control animals and changed in proportion to
      background ventilatory drive, increasing with metabolic acidosis (-6.7 mm Hg) and
      nonhypoxic peripheral chemoreceptor stimulation (almitrine; -5.9 mm Hg) and
      decreasing with metabolic alkalosis (-3.7 mm Hg). Hypoxia was the exception;
      DeltaPET(CO2) narrowed (-4.1 mm Hg) despite the accompanying hyperventilation.
      Thus, hyperventilation and hypocapnia, per se, widened the DeltaPET(CO2) thereby
      protecting against apnea and hypopnea, whereas reduced ventilatory drive and
      hypoventilation narrowed the DeltaPET(CO2) and increased the susceptibility to
      apnea. Hypoxia sensitized the ventilatory responsiveness to CO2 below eupnea and
      narrowed the DeltaPET(CO2); this effect of hypoxia was not attributable to an
      imbalance between peripheral and central chemoreceptor stimulation, per se. We
      conclude that the DeltaPET(CO2) and the ventilatory sensitivity to CO2 between
      eupnea and the apneic threshold are changeable in the face of variations in the
      magnitude, direction, and/or type of ventilatory stimulus, thereby altering the
      susceptibility for apnea, hypopnea, and periodic breathing in sleep.

PMID- 11991875
TI  - Dyspnea and decreased variability of breathing in patients with restrictive lung
      disease.
AB  - Patients with restrictive lung disease are typically dyspneic and have an
      increase in overall respiratory center drive, as a result of increased lung
      elasticity. When we subjected healthy volunteers to external elastic loads, their
      variability of breathing was lessened. Accordingly, we hypothesized that patients
      with restrictive lung disease display decreased variability of breathing and,
      also, that decreased variability of breathing is related to dyspnea. Breathing
      pattern was measured nonobtrusively over 1 hour in 10 patients with restrictive
      lung disease and in 7 healthy subjects. On a separate occasion, dyspnea was
      measured while all subjects copied different tidal volumes and frequencies.
      Compared with healthy subjects, the random fraction of breath variability was
      reduced in patients with restrictive lung disease: 27 times for expiratory time,
      12 times for tidal volume, and 6 times for inspiratory time (p < 0.01 in each
      instance). Conversely, the nonrandom, correlated fraction for tidal volume was
      increased almost 3-fold in the patients (p < 0.01). Small variations from average
      resting tidal volume caused marked increases in dyspnea in patients, and the
      relationship was parabolic (r2 = 0.97; p < 0.001). In conclusion, patients with
      restrictive lung disease adopt a tightly constrained breathing pattern, probably
      as a strategy for avoiding dyspnea.

PMID- 11991876
TI  - Effect of severe isolated unilateral and bilateral diaphragm weakness on exercise
      performance.
AB  - Patients with isolated diaphragm paralysis depend on recruitment of
      extradiaphragmatic respiratory muscles to increase ventilation, but little is
      known about exercise performance or the response of the inspiratory muscles to
      loaded breathing. By convention, unilateral diaphragm paralysis is regarded as a
      trivial condition whereas bilateral paralysis is considered to be potentially
      life-threatening. In fact, no data exist concerning exercise performance under
      these conditions. We studied incremental treadmill exercise performed by eight
      patients with bilateral diaphragm paralysis, eight patients with unilateral
      diaphragm paralysis, and eight age-matched control subjects. Respiratory muscle
      endurance (RME) was also measured by an inspiratory threshold loading method.
      Exercise time, compared with control subjects (671 seconds), was moderately
      reduced in unilateral diaphragm paralysis (512 seconds, p = 0.07) and further
      reduced in bilateral diaphragm paralysis (456 seconds, p = 0.02). Similarly, peak
      minute ventilation was lower in patients with unilateral diaphragm paralysis (84
      L x min(-1), p = 0.01) and in patients with bilateral diaphragm paralysis (69 L x
      min(-1), p = 0.001) compared with control subjects (114 L x min(-1)). However,
      patients with unilateral diaphragm paralysis and patients with bilateral
      diaphragm paralysis had increased ratios of peak oxygen consumption to peak
      minute ventilation compared with control subjects (p = 0.0007 and p < 0.0001,
      respectively). Nine patients had normal RME; exercise time was moderately
      increased in these patients (502 seconds) compared with seven patients with
      reduced RME (461 seconds). In conclusion, although exercise performance is
      impaired in bilateral diaphragm paralysis, these patients can sustain a
      reasonable exercise load, particularly if RME is preserved and compensatory
      mechanisms have developed. In addition, exercise tolerance is diminished in
      patients with unilateral diaphragm paralysis.

PMID- 11991877
TI  - ARDSNet lower tidal volume ventilatory strategy may generate intrinsic positive
      end-expiratory pressure in patients with acute respiratory distress syndrome.
AB  - The ARDSNet trial revealed that the use of a smaller tidal volume (VT) reduced
      mortality by 22%. However, three earlier studies that lowered VT did not find a
      decrease in mortality. We tested the hypothesis that the increased respiratory
      rate used in the ARDSNet lower VT strategy might have led to intrinsic positive
      end-expiratory pressure (PEEP(i)), raising total PEEP (PEEP(total)). Ten patients
      with acute respiratory distress syndrome (ARDS) were ventilated using the ARDSNet
      lower VT protocol. Respiratory rate was then reduced (10-15 breaths/minute) to
      obtain a VT of 12 ml/kg (ARDSNet traditional VT). PEEP on the ventilator
      (PEEP(nominal): 10.1 +/- 0.7 cm H2O), FIO2 (0.7 +/- 0.1), and minute ventilation
      (VE: 12.4 +/- 1.7 L/minute) were set using the ARDSNet protocol and maintained
      constant during the two ventilatory strategies. Values of airway pressure at end
      expiration of a regular breath (PEEP(external)) and 3-5 seconds after the onset
      of an end-expiratory occlusion (PEEP(total)) were measured. PEEP(i) was
      calculated by subtracting PEEP(external) from PEEP(total). PEEP(total) and
      PEEP(i) were, respectively, 16.3 +/- 2.9 and 5.8 +/- 3.0 cm H2O during the lower
      VT strategy and 11.7 +/- 0.9 and 1.4 +/- 1.0 cm H2O during the traditional VT
      strategy (p < 0.01). The reduced mortality observed with the ARDSNet strategy may
      have been due to the protective effect of a higher PEEP(total).

PMID- 11991878
TI  - Assessment of microvascular leakage via sputum induction: the role of substance P
      and neurokinin A in patients with asthma.
AB  - Microvascular leakage is an important feature of inflammation. However, the
      assessment of vascular leakage has seldom been used to monitor airway
      inflammation in asthma. The aim of this study was to determine the effect of
      inhaled substance P, a potent neurokinin 1 (NK1) agonist and mediator of plasma
      extravasation, on markers of microvascular leakage in induced sputum from
      patients with asthma. In a crossover study, sputum was induced before and 30
      minutes after inhalation of substance P or neurokinin A (as control) by 12
      subjects with atopic and mild, steroid-naive asthma. The levels of alpha2
      macroglobulin, ceruloplasmin, albumin, and fibrinogen were determined in induced
      sputum as markers of leakage. Substance P induced a significant increase in the
      levels of alpha2-macroglobulin, ceruloplasmin, and albumin in induced sputum
      (median fold change, 3.1, 2.2, and 2.9, respectively) (p < 0.013), whereas
      inhaled neurokinin A was not able to induce significant changes (p > 0.31). The
      increase in sputum leakage markers was not associated with the cumulative dose of
      substance P (p > 0.12). These results indicate that NK1 receptor stimulation
      causes a rapid increase in microvascular leakage as shown in induced sputum in
      patients with asthma. This investigational model of "dual induction" (first
      leakage, then sputum) may therefore be useful to test the antiexudative effect of
      newly develop drugs, such as NK1 antagonists.

PMID- 11991879
TI  - Effect of age on allergen-induced structural airway changes in brown Norway rats.
AB  - It remains to be fully established whether allergen-induced airway inflammation
      and remodeling are influenced by age. The aim of the present study was to compare
      allergen-induced airway changes in young and adult rats. Brown Norway rats were
      sensitized at 4 weeks of age (young) or 13 weeks of age (adult) and exposed to
      aerosolized ovalbumin (OA) or phosphate-buffered saline for 2 weeks. In both age
      groups OA exposure induced an increase in OA-specific Immunoglobulin E and in the
      number of peribronchial eosinophils. OA-challenged animals also developed an
      increase in total airway wall area, enhanced fibronectin deposition, and goblet
      cell hyperplasia. Both inflammatory and structural alterations were more
      pronounced in the airways of young compared with adult OA-exposed rats. The
      number of peribronchial eosinophils was increased in young animals (685.4 +/-
      75.0 versus 389.9 +/- 37.8/mm2 in adult rats; p < 0.001). A higher degree of
      goblet cell hyperplasia was observed in young rats (65.37 +/- 4.68 versus 34.74
      +/- 3.68/mm basement membrane in adult rats; p < 0.001) and area of fibronectin
      deposition in the airway wall was higher in young compared with adult animals
      (5.08 +/- 0.46 versus 3.62 +/- 0.29 microm2/microm basement membrane; p < 0.005).
      In conclusion, in young rats airways are more susceptible to allergen-induced
      inflammatory and structural airway changes.

PMID- 11991880
TI  - Association of rhinovirus infection with increased disease severity in acute
      bronchiolitis.
AB  - Respiratory syncytial virus (RSV) is the major pathogen responsible for acute
      bronchiolitis in infancy. However, evaluation of the relative importance of
      rhinovirus or multiple viral infections has been hampered by the lack of
      sensitive diagnostic methodologies. Therefore, in this study we used the reverse
      transcription-polymerase chain reaction for 11 respiratory pathogens to assess
      the etiology in infants with acute bronchiolitis and correlate it with clinical
      characteristics of the disease. Viruses were detected in 73.7% of patients. RSV
      was identified in 72.4% of virologically confirmed cases, rhinovirus in 29%,
      whereas multiple infections represented 19.5% of cases, most of which (69%) were
      combinations of rhinovirus with RSV. In a logistic regression model controlling
      for age, sex, birth weight, presence of fever, and day of disease on admission,
      the presence of rhinovirus was found to increase by approximately five-fold, the
      risk for severe disease. Multiple pathogens had a similar trend in the univariate
      analysis, which was eliminated in the multivariate model. Multiple virus cases
      were admitted to the hospital later in the course of their disease than unique
      pathogen cases, suggesting successive infections. In conclusion, rhinovirus is
      second only to RSV as a causative agent of bronchiolitis and is associated with
      more severe disease. The presence of more than one pathogen may influence the
      natural history of acute bronchiolitis.

PMID- 11991881
TI  - Increased interleukin-4 and decreased interferon-gamma in exhaled breath
      condensate of children with asthma.
AB  - Exhaled breath condensate analysis for noninvasive quantification of airway
      inflammation in asthma is a potentially useful research tool in children. There
      is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4,
      and Th1 cells, which secrete interferon (IFN)-gamma, in asthma. We measured
      concentrations of IL-4 and IFN-gamma in breath condensates of 37 children (11
      normal, 12 steroid-naive, and 14 steroid-treated children with asthma). Exhaled
      IFN-gamma was significantly lower in steroid-naive and steroid-treated children
      with asthma compared with normal control subjects (3.7 +/- 0.2 versus 5.1 +/- 0.4
      pg/ml, p < 0.01 and 4.1 versus 5.1 pg/ml, p < 0.05). By contrast, mean exhaled IL
      4 was elevated in asthma (53.7 +/- 4.2 pg/ml) compared with normal children (35.7
      +/- 6.2 pg/ml, p < 0.05) and concentrations were lower with steroid treatment
      (37.5 +/- 5.6 pg/ml, p < 0.05). Exhaled IL-4 was significantly lower in children
      with asthma on more than 600 microg inhaled steroid/day. The IL-4/IFN-gamma ratio
      was significantly greater in children with asthma compared with control children
      and the children with asthma on inhaled steroid therapy. We have shown for the
      first time that IFN-gamma and IL-4 can be assayed in exhaled breath condensate
      and shows an increased ratio of IL-4/IFN-gamma, consistent with predominance of
      Th2 cells in airways of children with asthma. Exhaled breath condensate analysis
      may have a useful role in studying allergic inflammation in childhood asthma.

PMID- 11991882
TI  - Infants with flow limitation at 4 weeks: outcome at 6 and 11 years.
AB  - Within a longitudinal study of lung function in 243 infants, we identified a
      group of 23 individuals with flow limitation in tidal expiration. In infancy,
      flow-limited children have reduced lung function and increased airway
      responsiveness (AR), and at 2 years of age they are diagnosed with asthma more
      frequently. We hypothesized that these observations would persist throughout
      childhood. Data from ages 3 to 11 years were analyzed. Only at 4 years of age did
      the flow-limited group have increased wheeze compared with other cohort members
      (odds ratio, 4.25; 95% confidence interval [CI], 1.11 to 16.2; p = 0.04; n =
      114). At 6 years of age, 117 cohort members were seen. The flow-limited group (n
      = 14) had greater AR (p = 0.009) and reduced mean FEV(1) (131 ml; 95% CI, 16 to
      246; p = 0.03) and FEF(25-75) (0.28 L/second; 95% CI, 0.05 to 0.52; p = 0.02). At
      11 years of age, 183 children were seen and the flow-limited group (n = 18) had
      greater AR (p = 0.02) and a trend toward reduced mean FEF(25-75) (0.24 L/second;
      95% CI, -0.02 to 0.49; p = 0.08). Atopy and parental asthma were not increased in
      the flow-limited group. We suggest that the physiologic abnormality that causes
      flow limitation in early infancy may identify an at-risk group, different from
      asthma, who have reduced lung function and increased airway responsiveness in
      later life.

PMID- 11991883
TI  - Prospective study of diet and decline in lung function in a general population.
AB  - We have investigated the relationship between decline in lung function and
      dietary intakes of magnesium, vitamin C, and other antioxidant vitamins in a
      general population cohort in Nottingham, United Kingdom. In 1991, we measured
      dietary intake by semiquantitative food frequency questionnaire, forced
      expiratory volume in 1 second (FEV1), and respiratory symptoms in a cross
      sectional survey of 2,633 adults aged 18-70. Nine years later we repeated these
      measures in 1,346 of these individuals. In cross-sectional analyses, after
      adjustment for smoking and other confounders, higher intakes of vitamin C and
      magnesium, but not vitamins A or E, were associated with higher levels of FEV1 in
      both 1991 and 2000. In longitudinal analysis with adjustment for confounders,
      decline in FEV1 between 1991 and 2000 was lower amongst those with higher average
      vitamin C intake by 50.8 ml (95% confidence interval, 3.8-97.9) per 100 mg of
      vitamin C per day, but was unrelated to magnesium intake. There was no
      relationship between decline in FEV1 and intake of vitamins A or E. This study
      suggests that a high dietary intake of vitamin C, or of foods rich in this
      vitamin, may reduce the rate of loss of lung function in adults and thereby help
      to prevent chronic obstructive pulmonary disease.

PMID- 11991884
TI  - The best peak expiratory flow is flow-limited and effort-independent in normal
      subjects.
AB  - Recently, it has been suggested that peak expiratory flow (PEF) may be determined
      by the wave speed flow-limiting mechanism. In six normal male subjects (age = 33
      +/- 8 years) performing expiratory forced vital capacity (FVC) maneuvers, a
      negative expiratory pressure (NEP) of -10 cm H2O was randomly applied at the
      beginning of maximal expiration to assess changes in PEF as compared with
      baseline. During FVC maneuvers, the expiratory effort was measured by changes in
      esophageal pressure (Pes), as either peak expiratory Pes-Pes at end expiratory
      lung volume (DeltaPes(peak)) or maximal rate of rise of Pes (dPes/dt(max)). In
      each experimental condition, at least three FVC maneuvers with comparable
      expiratory effort were selected for analysis for each subject. With similar
      DeltaPes(peak) (107.2 +/- 34.9 versus 111.7 +/- 40.5 cm H2O) and dPes/dt(max)
      (1181 +/- 518 versus 1177 +/- 546 cm H2O/second) PEF amounted to 10.84 +/- 1.08
      L/second and to 10.82 +/- 1.03 L/second with and without NEP, respectively. These
      data show that PEF obtained by normal subjects to the best of their abilities
      (best PEF) does not increase with NEP and indicate that the best PEF is a flow
      limited and effort-independent parameter, reflecting only lung and airways
      mechanics as the other subsequent maximal expiratory flows achieved during the
      FVC maneuver.

PMID- 11991885
TI  - Cardiopulmonary responses to exercise in women with sickle cell anemia.
AB  - Multiple factors contribute to exercise intolerance in patients with sickle cell
      anemia, but little information exists regarding the safety of maximal
      cardiopulmonary exercise testing (CPET) or the mechanisms of exercise limitation
      in these patients. The purpose of the present study was to examine these issues.
      Seventeen adult women with sickle cell anemia underwent symptom-limited maximal
      CPET using cycle ergometry and ramp protocols; blood gases and lactate
      concentrations were measured every 2 minutes. All patients completed CPET without
      complications. No patient demonstrated a mechanical ventilatory limitation to
      exercise or had evidence of myocardial ischemia. However, we observed three
      pathophysiologic patterns of response to exercise in these patients. Eleven
      patients had low peak VO2, low anaerobic threshold (AT), gas exchange
      abnormalities, and high ventilatory reserve; this pattern is consistent with
      exercise limitation due to pulmonary vascular disease in this patient subgroup.
      Three patients had low peak VO2, low AT, no gas exchange abnormalities, and a
      high heart rate reserve, a pattern consistent with peripheral vascular disease
      and/or a myopathy. The remaining three patients had low peak VO2, low AT, no gas
      exchange abnormalities, and a low heart rate reserve; this pattern of exercise
      limitation is best explained by anemia.

PMID- 11991886
TI  - The utility of albuterol nebulized with heliox during acute asthma exacerbations.
AB  - Heliox improves lung deposition of inhaled particles when compared with air or
      oxygen inhalation. We studied the spirometric effects of albuterol nebulized with
      heliox during emergency room visits for asthma exacerbations. Forty-five patients
      were randomized to receive albuterol nebulized with oxygen (control) versus
      heliox (n = 22 control and 23 heliox subjects). At baseline, demographics,
      outpatient asthma medications, vital signs, oxygen saturation, and forced
      expiratory volume in one second were not different between the two groups. Three
      consecutive albuterol treatments were given to each group. The heliox group had a
      significantly higher heart rate after albuterol nebulization compared with the
      control group. Following albuterol Treatment 1, the median change in forced
      expiratory volume in one second was 14.6% in the control group and 32.4% in the
      heliox group (p = 0.007). After Treatment 2, the results were 22.7% versus 51.5%,
      respectively (p = 0.007). After Treatment 3, the results were 26.6% versus 65.1%,
      respectively (p = 0.016). We conclude that during acute asthma exacerbations,
      albuterol nebulized with heliox leads to a more significant improvement in
      spirometry when compared with albuterol nebulized with oxygen. This is likely due
      to the low-density gas improving albuterol deposition in the distal airways.

PMID- 11991887
TI  - Heterozygosity for a surfactant protein C gene mutation associated with usual
      interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one
      kindred.
AB  - Familial pulmonary fibrosis is a heterogeneous group of interstitial lung
      diseases of unknown cause that is associated with multiple pathologic subsets.
      Mutations in the surfactant protein C (SP-C) gene (SFTPC) are associated with
      familial desquamative and nonspecific interstitial pneumonitis. Genetic studies
      in familial usual interstitial pneumonitis have been inconclusive. Using a
      candidate gene approach, we found a heterozygous exon 5 + 128 T-->A transversion
      of SFTPC in a large familial pulmonary fibrosis kindred, including adults with
      usual interstitial pneumonitis and children with cellular nonspecific
      interstitial pneumonitis. The mutation is predicted to substitute a glutamine for
      a conserved leucine residue and may hinder processing of SP-C precursor protein.
      SP-C precursor protein displayed aberrant subcellular localization by
      immunostaining. Electron microscopy of affected lung revealed alveolar type II
      cell atypia, with numerous abnormal lamellar bodies. Mouse lung epithelial cells
      transfected with the SFTPC mutation were notable for similar electron microscopy
      findings and for exaggerated cellular toxicity. We show that an SFTPC mutation
      segregates with the pulmonary fibrosis phenotype in this kindred and may cause
      type II cellular injury. The presence of two different pathologic diagnoses in
      affected relatives sharing this mutation indicates that in this kindred, these
      diseases may represent pleiotropic manifestations of the same central
      pathogenesis.

PMID- 11991888
TI  - Diesel exhaust particles enhance lung injury related to bacterial endotoxin
      through expression of proinflammatory cytokines, chemokines, and intercellular
      adhesion molecule-1.
AB  - Epidemiologic studies demonstrate acute and serious adverse effects of
      particulate air pollution on respiratory health, especially in people who are
      susceptible to bacterial infection. However, the underlying mechanism remains to
      be elucidated. To provide experimental evidence for the epidemiologic data, we
      determined the effects of diesel exhaust particles (DEP), major participants in
      particulate pollutants, on lung injury related to bacterial endotoxin in mice.
      Intratracheal instillation of DEPs synergistically enhanced lung injury related
      to endotoxin from gram-negative bacteria, which was characterized by neutrophil
      sequestration, interstitial edema, and alveolar hemorrhage. In the presence of
      endotoxin, DEPs further activated the nuclear translocation of p65 subunit of
      nuclear factor-kappaB (NF-kappaB) in the lung and increased the lung expression
      of intercellular adhesion molecule-1, interleukin-1beta, macrophage
      chemoattractant protein-1, keratinocyte chemoattractant (KC), macrophage
      inflammatory protein-1alpha, and Toll-like receptors. DEPs given alone increased
      the lung expression of Toll-like receptor 4 and the nuclear localization of p50
      subunit of NF-kappaB. The combined exposure to DEPs and endotoxin decreased
      nuclear localization of CCAAT/enhancer binding protein beta. These results
      provide the first experimental evidence that DEPs enhance neutrophilic lung
      inflammation related to bacterial endotoxin. The enhancement is mediated by the
      induction of proinflammatory molecules, likely through the expression of Toll
      like receptors and the activation of p65-containing dimer(s) of NF-kappaB, such
      as p65/p50.

PMID- 11991889
TI  - Is COPD also a disease of skeletal muscle?

PMID- 11991890
TI  - Adenosine monophosphate challenge and monitoring of airway response to
      antiinflammatory therapy.

PMID- 11991891
TI  - "Treatment of LTBI": selling point or semantic blunder?

PMID- 11991892
TI  - Treatment options for benign prostatic hyperplasia.

PMID- 11991893
TI  - A fresh new contract for general practitioners.

PMID- 11991894
TI  - Childhood drowning is a global concern.

PMID- 11991895
TI  - Genomics and global health.

PMID- 11991896
TI  - Paediatric asthma--a new virtual journal.

PMID- 11991897
TI  - Poor countries could lose out on benefits of genomic research.

PMID- 11991899
TI  - Australia acts to restrict IVF treatment to heterosexual couples.

PMID- 11991902
TI  - GMC to send out new guidelines on end of life decisions.

PMID- 11991905
TI  - Torture continues in post-election Zimbabwe.

PMID- 11991906
TI  - High Court rules that delays breach the rights of detained psychiatric patients.

PMID- 11991907
TI  - Every psychiatric ward should have a lead consultant, DoH says.

PMID- 11991908
TI  - Sexual dysfunction in men after treatment for lower urinary tract symptoms:
      evidence from randomised controlled trial.
AB  - OBJECTIVE: To examine the impact on sexual function of treatments for lower
      urinary tract symptoms in men. DESIGN: Multicentre pragmatic randomised
      controlled trial of standard surgery (transurethral resection of the prostate),
      non-contact laser therapy, and conservative management (no active intervention).
      SETTING: Three clinical centres in the United Kingdom. PARTICIPANTS: 340 men aged
      between 48 and 90 years with lower urinary tract symptoms related to benign
      prostatic enlargement. MAIN OUTCOME MEASURES: ICSsex questionnaire items
      concerned with erectile stiffness, ejaculatory volume, pain or discomfort on
      ejaculation, whether sex life was spoilt by urinary symptoms. RESULTS: Erectile
      and ejaculatory dysfunction were common (70%) and problematic at baseline and
      showed the expected trends with ageing. After treatment, reduced ejaculation was
      reported in all groups but was not significantly worse after standard surgery
      than after laser therapy. Erectile function was significantly improved after
      standard surgery; no significant difference was found between standard surgery
      and laser therapy (odds ratio 0.70, 95% confidence interval 0.36 to 1.38).
      Standard surgery was significantly better at relieving pain or discomfort on
      ejaculation than either conservative management (0.06, 0.007 to 0.49) or laser
      therapy (0.09, 0.01 to 0.73). CONCLUSIONS: Compared with laser therapy standard
      surgery for lower urinary tract symptoms has a beneficial effect on aspects of
      sexual function-particularly in improving erectile function and reducing reported
      pain or discomfort on ejaculation. Older men who need treatment and want to
      retain or improve sexual function may thus want to consider standard surgery
      rather than non-contact laser therapy.

PMID- 11991909
TI  - Randomised controlled trial of behavioural infant sleep intervention to improve
      infant sleep and maternal mood.
AB  - OBJECTIVE: To compare the effect of a behavioural sleep intervention with written
      information about normal sleep on infant sleep problems and maternal depression.
      DESIGN: Randomised controlled trial. SETTING: Well child clinics, Melbourne,
      Australia. PARTICIPANTS: 156 mothers of infants aged 6-12 months with severe
      sleep problems according to the parents. MAIN OUTCOME MEASURES: Maternal report
      of infant sleep problem; scores on Edinburgh postnatal depression scale at two
      and four months. INTERVENTION: Discussion on behavioural infant sleep
      intervention (controlled crying) delivered over three consultations. RESULTS: At
      two months more sleep problems had resolved in the intervention group than in the
      control group (53/76 v 36/76, P=0.005). Overall depression scores fell further in
      the intervention group than in the control group (mean change -3.7, 95%
      confidence interval -4.7 to -2.7, v -2.5, -1.7 to -3.4, P=0.06). For the subgroup
      of mothers with depression scores of 10 and over more sleep problems had resolved
      in the intervention group than in the control group (26/33 v 13/33, P=0.001). In
      this subgroup depression scores also fell further for intervention mothers than
      control mothers at two months (-6.0, -7.5 to -4.0, v -3.7, -4.9 to -2.6, P=0.01)
      and at four months (-6.5, -7.9 to 5.1 v -4.2, -5.9 to -2.5, P=0.04). By four
      months, changes in sleep problems and depression scores were similar.
      CONCLUSIONS: Behavioural intervention significantly reduces infant sleep problems
      at two but not four months. Maternal report of symptoms of depression decreased
      significantly at two months, and this was sustained at four months for mothers
      with high depression scores.

PMID- 11991910
TI  - Perceptions of stroke in the general public and patients with stroke: a
      qualitative study.
AB  - OBJECTIVES: To gain insight into people's thoughts on stroke and to inform the
      development of educational strategies in the community. DESIGN: Focus group
      discussions: two groups of people who had a stroke and their carers, and two
      groups of members of the general public. SETTING: New South Wales, Australia.
      PARTICIPANTS: 35 people participated: 11 from the general public, 14 people who
      had had a stroke, and 10 carers or partners. MAIN OUTCOME MEASURES: Views on risk
      factors, symptoms, treatment, information resources, and prevention. RESULTS: All
      groups reported similar knowledge of risk factors. People generally mentioned
      stress, diet, high blood pressure, age, and smoking as causes of stroke.
      Participants in the community group gave little attention to symptoms. Some
      participants who had had a stroke did not initially identify their experience as
      stroke because the symptoms were not the same as those they had read about. There
      were mixed feelings about the extent of involvement in management decisions
      during hospital admission. Some felt sufficiently involved, some wanted to be
      more involved, and others felt incapable of being actively involved. CONCLUSIONS:
      Symptoms of stroke are not easy to recognise because they vary so much.
      Presentation of information about stroke by hospital and community health
      services should be improved. Simple and understandable educational materials
      should be developed and their effectiveness monitored.

PMID- 11991911
TI  - In-hospital deaths as fraction of all deaths within 30 days of hospital admission
      for surgery: analysis of routine statistics.

PMID- 11991912
TI  - Preventing deaths by drowning in children in the United Kingdom: have we made
      progress in 10 years? Population based incidence study.

PMID- 11991913
TI  - Effects of community based nurses specialising in Parkinson's disease on health
      outcome and costs: randomised controlled trial.
AB  - OBJECTIVE: To determine the effects of community based nurses specialising in
      Parkinson's disease on health outcomes and healthcare costs. DESIGN: Two year
      randomised controlled trial. SETTING: 438 general practices in nine randomly
      selected health authority areas of England. PARTICIPANTS: 1859 patients with
      Parkinson's disease identified by the participating general practices. MAIN
      OUTCOME MEASURES: Survival, stand-up test, dot in square test, bone fracture,
      global health question, PDQ-39, Euroqol, and healthcare costs. RESULTS: After two
      years 315 (17.3%) patients had died, although mortality did not differ between
      those who were attended by nurse specialists and those receiving standard care
      from their general practitioner (hazard ratio for nurse group v control group
      0.91, 95% confidence interval 0.73 to 1.13). No significant differences were
      found between the two groups for the stand-up test (odds ratio 1.15, 0.93 to
      1.42) and dot in square score (difference -0.7, -3.25 to 1.84). Scores on the
      global health question were significantly better in patients attended by nurse
      specialists than in controls (difference -0.23, -0.4 to -0.06), but no difference
      was observed in the results of the PDQ-39 or Euroqol questionnaires. Direct costs
      for patient health care increased by an average of 2658 pounds sterling during
      the study, although not differentially between groups: the average increase was
      266 pounds sterling lower among patients attended by a nurse specialist (-981
      pounds sterling to 449 pounds sterling ). CONCLUSIONS: Nurse specialists in
      Parkinson's disease had little effect on the clinical condition of patients, but
      they did improve their patients' sense of wellbeing, with no increase in
      patients' healthcare costs.

PMID- 11991914
TI  - Genital herpes.

PMID- 11991915
TI  - Computed tomography in clinical practice.

PMID- 11991916
TI  - Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with
      asthma receiving high dose inhaled fluticasone propionate.

PMID- 11991917
TI  - Exercise tolerance testing.

PMID- 11991918
TI  - Presumed benefit: lessons from the American experience with marrow
      transplantation for breast cancer.

PMID- 11991919
TI  - Why does NICE not recommend laparoscopic herniorraphy?

PMID- 11991920
TI  - New Medical Education Standards Board will lower standards.

PMID- 11991921
TI  - Mortality and volume of cases in paediatric cardiac surgery. Paper confirms poor
      quality of paediatric heart surgery at Bristol during 1991-5.

PMID- 11991922
TI  - A case of murder and the BMJ. Personal paper is anything but balanced
      interpretation.

PMID- 11991923
TI  - Depression and unintended pregnancy in young women. Paper raises at least three
      concerns.

PMID- 11991924
TI  - Hound of the Baskervilles effect. What about the good days?

PMID- 11991926
TI  - Friends and family are good (and cheap) life coaches.

PMID- 11991925
TI  - New act regulating human organ transplantation could facilitate organ donation.

PMID- 11991927
TI  - GPs should reduce antibiotic use with alternative treatments.

PMID- 11991928
TI  - Topical negative pressure may help chronic wound healing.

PMID- 11991929
TI  - Study of effect of delays on ovarian cancer was weak.

PMID- 11991930
TI  - Using twin studies to label disease as genetic or environmental is inappropriate.

PMID- 11991931
TI  - Removing barriers for disabled people would be giant leap.

PMID- 11991932
TI  - Brain denies being forbidding and insensitive to change.

PMID- 11991937
TI  - Majorities and individuals.

PMID- 11991938
TI  - Comment on Vicki Brower's article 'Harnessing the immune system to battle
      Alzheimer's' in EMBO reports, March 2002.

PMID- 11991939
TI  - Climbing mountains: a profile of Max Perutz 1914-2002: a life in science.

PMID- 11991940
TI  - Search and retrieve. Large-scale data generation is becoming increasingly
      important in biological research. But how good are the tools to make sense of the
      data?

PMID- 11991941
TI  - Budget wars in genomics. Should large-scale functional genomics and proteomics be
      funded by the public or the private sector?

PMID- 11991942
TI  - Growing greener. The impact of integrated pest management.

PMID- 11991943
TI  - Injection of confidence. The recent controversy in the UK has led to falling MMR
      vaccination rates.

PMID- 11991944
TI  - Signalling takes control of nucleo-cytoplasmic trafficking. Workshop on signal
      regulated nuclear transport.

PMID- 11991945
TI  - Understanding cancer: from the gene to the organism. Conference on genes and
      cancer.

PMID- 11991946
TI  - ROS, stress-activated kinases and stress signaling in cancer.
AB  - Anticancer therapy is frequently efficient in early stages of the disease,
      whereas advanced tumors are usually resistant to the same treatments. The
      molecular basis for this change is not entirely understood. Many anticancer
      agents are DNA- or cytoskeleton-damaging drugs that show some specificity towards
      dividing cells. However, recent studies show that these agents also activate
      stress-signaling cascades that may play a role in eliciting the observed
      therapeutic effects. We discuss recent findings that suggest that induction of
      stress signaling in oncogenically transformed cells is integrated into apoptotic
      pathways. Reactive oxygen species (ROS) and stress-activated protein kinases
      (SAPKs), which are potentiated in recently transformed cells, emerge as key
      effectors of cell death. In advanced tumors, however, these agents are
      downregulated and, consequently, death signaling is suppressed. Such changes in
      ROS and SAPK activity levels during the course of tumor development may underlie
      the changes in responsiveness to anticancer therapy.

PMID- 11991947
TI  - Voltage dependence and pH regulation of human polycystin-2-mediated cation
      channel activity.
AB  - Polycystin-2, the product of the human PKD2 gene, whose mutations cause autosomal
      dominant polycystic kidney disease, is a large conductance, Ca(2+)-permeable non
      selective cation channel. Polycystin-2 is functionally expressed in the apical
      membrane of the human syncytiotrophoblast, where it may play a role in the
      control of fetal electrolyte homeostasis. Little is known, however, about the
      mechanisms that regulate polycystin-2 channel function. In this study, the role
      of pH in the regulation of polycystin-2 was assessed by ion channel
      reconstitution of both apical membranes of human syncytiotrophoblast and the
      purified FLAG-tagged protein from in vitro transcribed/translated material. A
      kinetic analysis of single channel currents, including dwell time histograms,
      confirmed two open and two close states for spontaneous channel behavior and a
      strong voltage dependence of the open probability of the channel (P(o)). A
      reduction of cis pH (pH(cis)) decreased P(o) and shifted the voltage dependence
      of channel function but had no effect on the single channel conductance. An
      increase in pH(cis), in contrast, increased NP(o) (channel number times P(o)).
      Elimination of the H(+) chemical gradient did not reverse the low pH(cis)
      inhibition of polycystin-2. Similar findings confirmed the pH effect on the in
      vitro translated, FLAG-tagged purified polycystin-2. The data indicate the
      presence of an H(+) ion regulatory site in the channel protein, which is
      accessible from the cytoplasmic side of the protein. This protonation site
      controls polycystin-2 cation-selective channel activity.

PMID- 11991948
TI  - Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate
      lyase. Structures of complexes with the substrate.
AB  - Hyaluronate lyase enzymes degrade hyaluronan, the main polysaccharide component
      of the host connective tissues, predominantly into unsaturated disaccharide
      units, thereby destroying the normal connective tissue structure and exposing the
      tissue cells to various endo- and exogenous factors, including bacterial toxins.
      The crystal structures of Streptococcus pneumoniae hyaluronate lyase with tetra-
      and hexasaccharide hyaluronan substrates bound in the active site were determined
      at 1.52- and 2.0-A resolution, respectively. Hexasaccharide is the longest
      substrate segment that binds entirely within the active site of these enzymes.
      The enzyme residues responsible for substrate binding, positioning, catalysis,
      and product release were thereby identified and their specific roles
      characterized. The involvement of three residues in catalysis, Asn(349),
      His(399), and Tyr(408), is confirmed, and the details of proton acceptance and
      donation within the catalytic machinery are described. The mechanism of
      processivity of the enzyme is analyzed. The flexibility (allosteric) behavior of
      the enzyme may be understood in terms of the results of flexibility analysis of
      this protein, which identified two modes of motion that are also proposed to be
      involved in the hyaluronan degradation process. The first motion describes an
      opening and closing of the catalytic cleft located between the alpha- and beta
      domains. The second motion demonstrates the mobility of a binding cleft, which
      may facilitate the binding of the negatively charged hyaluronan to the enzyme.

PMID- 11991949
TI  - Molecular cloning and characterization of chick sialoprotein associated with
      cones and rods, a developmentally regulated glycoprotein of interphotoreceptor
      matrix.
AB  - MY-174 is an IgM class monoclonal antibody originally established against chick
      PG-M/versican. The antibody specifically stains the photoreceptor layer, where we
      recently reported an absence of PG-M/versican. In this study, we re-characterized
      the antibody and identified the molecule that reacts to MY-174 at the
      photoreceptor layer. Immunohistochemistry localized the antigen to the matrix
      surrounding photoreceptors. A variety of glycosidase digestions showed that the
      antigen is the 150-kDa glycoprotein that has sialylated N- and O-linked
      glycoconjugates having a molecular mass of more than 30-kDa. The peptide
      sequences obtained from purified MY-174 antigen showed we had sequenced a full
      length cDNA with an open reading frame of 2787 base pairs, encoding a polypeptide
      of 928 amino acids, with 56 and 54% identities to human and mouse sialoprotein
      associated with cones and rods (SPACRs), respectively, and with the structural
      features observed in SPACRs. The specific sialylated O-glycoconjugates here are
      involved in the epitope structure for MY-174. SPACR first appeared by embryonic
      days 15-16, and expression increased with developmental age, paralleling the
      adhesion between neural retina and retinal pigment epithelium. Thus, we concluded
      that the MY-174 antigen at the photoreceptor layer, a developmentally regulated
      glycoprotein, is identical to chick SPACR and may be involved in a novel system
      mediating adhesion between neural retina and retinal pigment epithelium.

PMID- 11991950
TI  - Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor
      pathway in primary human hepatocytes.
AB  - The fully active dihydroxylated metabolite of vitamin D(3) induces the expression
      of CYP3A4 and, to a lesser extent, CYP2B6 and CYP2C9 genes in normal
      differentiated primary human hepatocytes. Electrophoretic mobility shift assays
      and cotransfection in HepG2 cells using wild-type and mutated oligonucleotides
      revealed that the vitamin D receptor (VDR) binds and transactivates those
      xenobiotic-responsive elements (ER6, DR3, and DR4) previously identified in
      CYP3A4, CYP2B6, and CYP2C9 promoters and shown to be targeted by the pregnane X
      receptor (PXR) and/or the constitutive androstane receptor (CAR). Full VDR
      response of various CYP3A4 heterologous/homologous promoter-reporter constructs
      requires both the proximal ER6 and the distal DR3 motifs, as observed previously
      with rifampicin-activated PXR. Cotransfection of a CYP3A4 homologous promoter
      reporter construct (including distal and proximal PXR-binding motifs) and of PXR
      or CAR expression vectors in HepG2 cells revealed the ability of these receptors
      to compete with VDR for transcriptional regulation of CYP3A4. In conclusion, this
      work suggests that VDR, PXR, and CAR control the basal and inducible expression
      of several CYP genes through competitive interaction with the same battery of
      responsive elements.

PMID- 11991951
TI  - Ets-1 regulates fli-1 expression in endothelial cells. Identification of ETS
      binding sites in the fli-1 gene promoter.
AB  - To understand the role of the Ets-1 transcription factor during angiogenesis, we
      have overexpressed it in endothelial cells and analyzed the levels of expression
      of several candidate target genes involved in angiogenesis. The transcripts
      levels of the ETS transcription factor fli-1 are specifically up-regulated in
      endothelial cells, which overexpress Ets-1, but not in fibroblasts. Analysis of
      the promoter of the mouse fli-1 gene reveals that the 1-kb region that comprises
      the transcription starts and part of exon 1 is responsible for the response of
      the promoter to Ets-1. The -270/-41 fragment contains two known Spi-1-responding
      Ets binding sites (EBS), which are also necessary for the activation by Ets-1. In
      contrast to Spi-1, a third EBS is necessary for the full response of this
      promoter fragment to Ets-1. The rest of the promoter activity has been located in
      the -986/-505 region, where three active EBSs have been identified. Furthermore,
      endogenous Fli-1 was found to be bound to its own gene promoter and to be able to
      promote the transactivation of its gene. These results suggest that Ets-1
      activates an auto-regulatory loop of expression of fli-1 in endothelial cells, a
      mechanism that could have significant implications for the endothelial cell fate.

PMID- 11991952
TI  - Site-directed glycosylation tagging of functional Kir2.1 reveals that the
      putative pore-forming segment is extracellular.
AB  - Inwardly rectifying K+ channels or Kirs are a large gene family and have been
      predicted to have two transmembrane segments, M1 and M2, intracellular N and C
      termini, and two extracellular loops, E1 and E2, separated by an intramembranous
      pore-forming segment, H5. H5 contains a stretch of eight residues that are
      similar in voltage-dependent K+ channels, Kvs, and this stretch is called the
      signature sequence of K+ channels. Because mutations in this sequence altered
      selectivity in Kvs, it has been designated as the selectivity filter. Previously,
      we used N-glycosylation substitution mutants to map the extracellular topology of
      a weak inwardly rectifying K+ channel, Kir1.1 or ROMK1, and found that the entire
      H5 segment was extracellular. We now report utilization of introduced N
      glycosylation sites, NX(S/T), at positions Ser(128) in E1, and Gln(140),
      Ileu(143), and Phe(147) in the H5 sequence of a strong inwardly rectifying K+
      channel, Kir2.1. Furthermore, we show that biotinylated channel proteins with N
      linked oligosaccharides attached at positions 140 and 143 in the signature
      sequence are located at the cell surface. Mutant channels were functional as
      detected by whole-cell and single-channel recordings. Unlike Kir1.1, position
      Lys(117) was not occupied. We conclude that, for yet another K+ channel, the
      invariant G(Y/F)G sequence is extracellular rather than intramembranous.

PMID- 11991953
TI  - The binding of Xanthophylls to the bulk light-harvesting complex of photosystem
      II of higher plants. A specific requirement for carotenoids with a 3-hydroxy-beta
      end group.
AB  - The pigment composition of the light-harvesting complexes (LHCs) of higher plants
      is highly conserved. The bulk complex (LHCIIb) binds three xanthophyll molecules
      in combination with chlorophyll (Chl) a and b. The structural requirements for
      binding xanthophylls to LHCIIb have been examined using an in vitro
      reconstitution procedure. Reassembly of the monomeric recombinant LHCIIb was
      performed using a wide range of native and nonnative xanthophylls, and a specific
      requirement for the presence of a hydroxy group at C-3 on a single beta-end group
      was identified. The presence of additional substituents (e.g. at C-4) did not
      interfere with xanthophyll binding, but they could not, on their own, support
      reassembly. cis isomers of zeaxanthin, violaxanthin, and lutein were not bound,
      whereas all-trans-neoxanthin and different chiral forms of lutein and zeaxanthin
      were incorporated into the complex. The C-3 and C-3' diols lactucaxanthin (a
      carotenoid native to many plant LHCs) and eschscholtzxanthin (a retro-carotenoid)
      both behaved very differently from lutein and zeaxanthin in that they would not
      support complex reassembly when used alone. Lactucaxanthin could, however, be
      bound when lutein was also present, and it showed a high affinity for xanthophyll
      binding site N1. In the presence of lutein, lactucaxanthin was readily bound to
      at least one lutein-binding site, suggesting that the ability to bind to the
      complex and initiate protein folding may be dependent on different structural
      features of the carotenoid molecule. The importance of carotenoid end group
      structure and ring-to-chain conformation around the C-6-C-7 torsion angle of the
      carotenoid molecule in binding and complex reassembly is discussed.

PMID- 11991954
TI  - Transcription factor NFIC undergoes N-glycosylation during early mammary gland
      involution.
AB  - Expression of a 74-kDa nuclear factor I (NFI) protein is triggered in early
      involution in the mouse mammary gland, and its expression correlates with
      enhanced occupation of a twin (NFI) binding element in the clusterin promoter, a
      gene whose transcription is induced at this time (Furlong, E. E., Keon, N. K.,
      Thornton, F. D., Rein, T., and Martin, F. (1996) J. Biol. Chem. 271, 29688
      29697). We now identify this 74-kDa NFI as an NFIC isoform based on its
      interaction in Western analysis with two NFIC-specific antibodies. A transition
      from the expression of a 49-kDa NFIC in lactation to the expression of the 74-kDa
      NFIC in early involution is demonstrated. We show that the 74-kDa NFIC binds
      specifically to concanavalin A (ConA) and that this binding can be reversed by
      the specific ConA ligands, methyl alpha-D-mannopyranoside and methyl alpha-D
      glucopyranoside. In addition, its apparent molecular size was reduced to
      approximately 63 kDa by treatment with the peptide N-glycosidase. The 49-kDa
      lactation-associated NFIC did not bind ConA nor was it affected by peptide N
      glycosidase. Tunicamycin, a specific inhibitor of N-glycosylation, blocked
      formation of the 74-kDa NFI in involuting mouse mammary gland in vivo when
      delivered from implanted Elvax depot pellets. Finally, the production of the ConA
      binding activity could be reiterated in "mammospheres" formed from primary mouse
      mammary epithelial cells associated with a laminin-rich extracellular matrix.
      Synthesis of the 74-kDa NFIC was also inhibited in this setting by tunicamycin.
      Thus, involution triggers the production of an NFIC isoform that is post
      translationally modified by N-glycosylation. We further show, by using
      quantitative competitive reverse transcriptase-PCR, that there is increased
      expression of the major mouse mammary NFIC mRNA transcript, mNFIC2, in early
      involution, suggesting that the involution-associated change in NFIC expression
      also has a transcriptional contribution.

PMID- 11991955
TI  - The reactivity and oxidation pathway of cysteine 232 in recombinant human alpha 1
      antitrypsin.
AB  - Oxidative damage to the sulfur-containing amino acids, methionine and cysteine,
      is a major concern in biotechnology and medicine. alpha1-Antitrypsin, which is a
      metastable and conformationally flexible protein that belongs to the serpin
      family of protease inhibitors, contains nine methionines and a single cysteine in
      its primary sequence. Although it is known that methionine oxidation in the
      protein active site results in a loss of biological activity, there is little
      specific knowledge regarding the reactivity of its unpaired thiol, Cys-232. In
      this study, the thiol-modifying reagent NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3
      diazole) was used to label peroxide-modified alpha1-antitrypsin and demonstrate
      that the Cys-232 in vitro oxidation pathway begins with a stable sulfenic acid
      intermediate and is followed by the formation of sulfinic and cysteic acid in
      successive steps. pH-dependent reactivity with hydrogen peroxide showed that Cys
      232 has a pK(a) of 6.86 +/- 0.05, a value that is more than 1.5 pH units lower
      than that of a typical protein thiol. pH-induced conformational changes in the
      region surrounding Cys-232 were also examined and indicate that mildly acidic
      conditions induce a conformation that enhances Cys-232 reactivity. In summary,
      this work provides new insights into alpha1-antitrypsin reactivity in oxidizing
      environments and shows that a unique structural environment renders its unpaired
      thiol, Cys-232, its most reactive amino acid.

PMID- 11991956
TI  - Binding of the antimicrobial peptide temporin L to liposomes assessed by Trp
      fluorescence.
AB  - The structure and membrane topology of the antimicrobial peptide temporin L
      (FVQWFSKFLGRIL- NH(2)) were studied using liposomes as model bilayers. Circular
      dichroic spectra revealed temporin L to adopt an alpha-helical conformation when
      bound to liposomes. Binding of temporin L to liposomes induced significant blue
      shifts of the emission spectra of the single Trp residue (Trp(4)) and also
      changed its quantum yield. The observed changes in the characteristics of the
      Trp(4) fluorescence are in keeping with the insertion of this residue into the
      hydrophobic region of the liposomal bilayers. Access of the aqueous quencher
      acrylamide to Trp(4) decreased in the sequence 1-stearoyl-2-oleoyl-sn-glycero-3
      phosphocholine (SOPC)/cholesterol (X(chol) = 0.1) > SOPC > SOPC/1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphoglycerol (POPG, X(POPG) = 0.1) > SOPC/POPG (X(POPG) =
      0.2) approximately SOPC/POPG (X(POPG) = 0.4), where X represents molar fraction
      of the indicated lipid. Whereas quenching of Trp(4) by brominated phospholipids
      was significant in SOPC liposomes, the quenching efficiency was enhanced when the
      vesicles contained POPG. The depth of insertion of Trp(4) into lipid bilayers was
      calculated by both the parallax method and distribution analysis and revealed
      this residue to reside at an average distance of d approximately 8.0 +/- 0.5 A
      from the center of both SOPC and SOPC/POPG bilayers. However, in the presence of
      cholesterol, d was increased to 9.5 +/- 0.5 A, thus revealing Trp(4) to become
      accommodated more superficially in the bilayer. The above data suggest the
      presence of two populations of temporin L in SOPC- and POPG-containing membranes
      with parallel and perpendicular orientation with respect to the plane of the
      membrane surface.

PMID- 11991957
TI  - The effect of additions of fluorine to the diet of the rat on the quality of the
      teeth. 1925. Studies on experimental rickets. XXI. An experimental demonstration
      of the existence of a vitamin which promotes calcium deposition. 1922. The effect
      of additions of fluorine to the diet of the rat on the quality of the teeth.
      1925.

PMID- 11991958
TI  - Transfer, incorporation, and substitution of envelope fusion proteins among
      members of the Baculoviridae, Orthomyxoviridae, and Metaviridae (insect
      retrovirus) families.

PMID- 11991959
TI  - Immunization with surface antigen vaccine alone and after treatment with 1-(2
      fluoro-5-methyl-beta-L-arabinofuranosyl)-uracil (L-FMAU) breaks humoral and cell
      mediated immune tolerance in chronic woodchuck hepatitis virus infection.
AB  - Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) were
      treated with the antiviral drug 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)
      uracil (L-FMAU) or placebo for 32 weeks. Half the woodchucks in each group then
      received four injections of surface antigen vaccine during the next 16 weeks.
      Vaccination alone elicited a low-level antibody response to surface antigen in
      most carriers but did not affect serum WHV DNA and surface antigen. Carriers
      treated first with L-FMAU to reduce serum WHV DNA and surface antigen and then
      vaccinated had a similar low-level antibody response to surface antigen.
      Following vaccinations, cell-mediated immunity to surface antigen was
      demonstrated in both groups, independent of serum viral and antigen load, but was
      significantly enhanced in woodchucks treated with L-FMAU and was broadened to
      include other viral antigens (core, e, and x antigens and selected core
      peptides). Cell-mediated immunity and antibody responses to surface antigen were
      observed after drug discontinuation in half of the carriers that received L-FMAU
      alone. Surface antigen vaccine alone or in combination with drug broke humoral
      and cell-mediated immune tolerance in chronic WHV infection, but the combination
      with drug was more effective. This suggested that a high viral and antigen load
      in carriers is important in maintaining immunologic tolerance during chronicity.
      The humoral and cellular immunity associated with the combination of L-FMAU and
      vaccine resembled that observed in self-limited WHV infection. Such combination
      therapy represents a potentially useful approach to the control of chronic
      hepatitis B virus infection in humans.

PMID- 11991960
TI  - Envelope glycoprotein incorporation, not shedding of surface envelope
      glycoprotein (gp120/SU), Is the primary determinant of SU content of purified
      human immunodeficiency virus type 1 and simian immunodeficiency virus.
AB  - Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus
      (SIV) particles typically contain small amounts of the surface envelope protein
      (SU), and this is widely believed to be due to shedding of SU from mature
      virions. We purified proteins from HIV-1 and SIV isolates using procedures which
      allow quantitative measurements of viral protein content and determination of the
      ratios of gag- and env-encoded proteins in virions. All of the HIV-1 and most of
      the SIV isolates examined contained low levels of envelope proteins, with Gag:Env
      ratios of approximately 60:1. Based on an estimate of 1,200 to 2,500 Gag
      molecules per virion, this corresponds to an average of between 21 and 42 SU
      molecules, or between 7 and 14 trimers, per particle. In contrast, some SIV
      isolates contained levels of SU at least 10-fold greater than SU from HIV-1
      isolates. Quantification of relative amounts of SU and transmembrane envelope
      protein (TM) provides a means to assess the impact of SU shedding on virion SU
      content, since such shedding would be expected to result in a molar excess of TM
      over SU on virions that had shed SU. With one exception, viruses with sufficient
      SU and TM to allow quantification were found to have approximately equivalent
      molar amounts of SU and TM. The quantity of SU associated with virions and the
      SU:TM ratios were not significantly changed during multiple freeze-thaw cycles or
      purification through sucrose gradients. Exposure of purified HIV-1 and SIV to
      temperatures of 55 degrees C or greater for 1 h resulted in loss of most of the
      SU from the virus but retention of TM. Incubation of purified virus with soluble
      CD4 at 37 degrees C resulted in no appreciable loss of SU from either SIV or HIV
      1. These results indicate that the association of SU and TM on the purified
      virions studied is quite stable. These findings suggest that incorporation of SU
      TM complexes into the viral membrane may be the primary factor determining the
      quantity of SU associated with SIV and HIV-1 virions, rather than shedding of SU
      from mature virions.

PMID- 11991961
TI  - Genetic analysis of sequences in the 3' nontranslated region of hepatitis C virus
      that are important for RNA replication.
AB  - The genome of the hepatitis C virus (HCV) is a plus-strand RNA molecule that
      carries a single long open reading frame. It is flanked at either end by highly
      conserved nontranslated regions (NTRs) that mediate crucial steps in the viral
      life cycle. The 3' NTR of HCV has a tripartite structure composed of an about 40
      nucleotide variable region, a poly(U/UC) tract that has a heterogeneous length,
      and a highly conserved 98-nucleotide 3'-terminal sequence designated the X tail
      or 3'X. Conflicting data as to the role the sequences in the 3' NTR play in RNA
      replication have been reported. By using the HCV replicon system, which is based
      on the self-replication of subgenomic HCV RNAs in human hepatoma cell line Huh-7,
      we mapped in this study the sequences in the 3' NTR required for RNA replication.
      We found that a mutant with a complete deletion of the variable region is viable
      but that replication is reduced significantly. Only replicons in which the
      poly(U/UC) tract was replaced by a homouridine stretch of at least 26 nucleotides
      were able to replicate, whereas RNAs with homopolymeric guanine, adenine, or
      cytosine sequences were inactive. Deletions of individual or all stem-loop
      structures in 3'X were not tolerated, demonstrating that this region is most
      crucial for efficient RNA replication. Finally, we found that none of these
      deletions or substitutions within the 3' NTR affected RNA stability or
      translation, demonstrating that the primary effect of the mutations was on RNA
      replication. These data represent the first detailed mapping of sequences in the
      3' NTR assumed to act as a promoter for initiation of minus-strand RNA synthesis.

PMID- 11991962
TI  - Characterization of CHAT and Cox type 1 live-attenuated poliovirus vaccine
      strains.
AB  - CHAT and Cox type 1 live-attenuated poliovirus strains were developed in the
      1950s to be used as vaccines for humans. This paper describes their
      characterization with respect to virulence, sensitivity for growth at high
      temperatures, and complete nucleotide and amino acid sequences. The results are
      compared to those for their common parental wild virus, the Mahoney strain, and
      to those for two other poliovirus strains derived from Mahoney, the Sabin 1
      vaccine strain and the mouse-adapted LS-a virus. Analysis of four isolates from
      cases of vaccine-associated paralytic poliomyelitis related to the CHAT vaccine
      revealed genetic and phenotypic properties of the CHAT strain following
      replication in the human gut. CHAT-VAPP strain 134 contained a genome highly
      evolved from that of CHAT (1.1% nucleotide differences), suggesting long-term
      circulation of a vaccine-derived strain in the human population. The molecular
      mechanisms of attenuation and evolution of poliovirus in humans are discussed in
      the context of the global polio eradication initiative.

PMID- 11991963
TI  - phi X174 genome-capsid interactions influence the biophysical properties of the
      virion: evidence for a scaffolding-like function for the genome during the final
      stages of morphogenesis.
AB  - During the final stages of phi X174 morphogenesis, there is an 8.5-A radial
      collapse of coat proteins around the packaged genome, which is tethered to the
      capsid's inner surface by the DNA-binding protein. Two approaches were taken to
      determine whether protein-DNA interactions affect the properties of the mature
      virion and thus the final stages of morphogenesis. In the first approach, genome
      capsid associations were altered with mutant DNA-binding proteins. The resulting
      particles differed from the wild-type virion in density, native gel migration,
      and host cell recognition. Differences in native gel migration were especially
      pronounced. However, no differences in protein stoichiometries were detected. An
      extragenic second-site suppressor of the mutant DNA-binding protein restores all
      assayed properties to near wild-type values. In the second approach, phi X174 was
      packaged with foreign, single-stranded, covalently closed, circular DNA molecules
      identical in length to the phi X174 genome. The resulting particles exhibited
      native gel migration rates that significantly differed from the wild type. The
      results of these experiments suggest that the structure of the genome and/or its
      association with the capsid's inner surface may perform a scaffolding-like
      function during the procapsid-to- virion transition.

PMID- 11991964
TI  - Modifications of the human immunodeficiency virus envelope glycoprotein enhance
      immunogenicity for genetic immunization.
AB  - In this study, we have investigated the effect of specific mutations in human
      immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an
      effort to improve humoral immune responses to this glycoprotein by DNA
      vaccination. Mice were injected with plasmid expression vectors encoding HIV Env
      with modifications in regions that might affect this response. Elimination of
      conserved glycosylation sites did not substantially enhance humoral or cytotoxic
      T-lymphocyte (CTL) immunity. In contrast, a modified gp140 with different COOH
      terminal mutations intended to mimic a fusion intermediate and stabilize trimer
      formation enhanced humoral immunity without reducing the efficacy of the CTL
      response. This mutant, with deletions in the cleavage site, fusogenic domain, and
      spacing of heptad repeats 1 and 2, retained native antigenic conformational
      determinants as defined by binding to known monoclonal antibodies or CD4,
      oligomer formation, and virus neutralization in vitro. Importantly, this modified
      Env, gp140 Delta CFI, stimulated the antibody response to native gp160 while it
      retained its ability to induce a CTL response, a desirable feature for an AIDS
      vaccine.

PMID- 11991965
TI  - Infection of cells with human cytomegalovirus during S phase results in a
      blockade to immediate-early gene expression that can be overcome by inhibition of
      the proteasome.
AB  - Cells infected with human cytomegalovirus (HCMV) after commencing DNA replication
      do not initiate viral immediate-early (IE) gene expression and divide before
      arresting. To determine the nature of this blockade, we examined cells that were
      infected 24 h after release from G(0) using immunofluorescence, laser scanning
      cytometry, and fluorescence-activated cell sorting (FACS) analysis. Approximately
      40 to 50% of the cells had 2N DNA content, became IE(+) in the first 12 h, and
      arrested. Most but not all of the cells with >2N DNA content did not express IE
      antigens until after mitosis. To define the small population of IE(+) cells that
      gradually accumulated within the S and G(2)/M compartments, cells were pulsed
      with bromodeoxyuridine (BrdU) just prior to S-phase infection and analyzed at 12
      h postinfection for IE gene expression, BrdU positivity, and cell cycle position.
      Most of the BrdU(+) cells were IE(-) and had progressed into G(2)/M or back to
      G(1). The majority of the IE(+) cells in S and G(2)/M were BrdU(-). Only a few
      cells were IE(+) BrdU(+), and they resided in G(2)/M. Multipoint BrdU pulse
      labeling revealed that, compared to cells actively synthesizing DNA at the
      beginning of the infection, a greater percentage of the cells that initiated DNA
      replication 4 h later could express IE antigens and proceed into S.
      Synchronization of the cells with aphidicolin also indicated that the blockade to
      the activation of IE gene expression was established in cells soon after
      initiation of DNA replication. It appears that a short-lived protein in S-phase
      cells may be required for IE gene expression, as it is partially restored by
      treatment with the proteasome inhibitor MG132.

PMID- 11991966
TI  - In vitro selection and characterization of influenza A (A/N9) virus variants
      resistant to a novel neuraminidase inhibitor, A-315675.
AB  - With the recent introduction of neuraminidase (NA) inhibitors into clinical
      practice for the treatment of influenza virus infections, considerable attention
      has been focused on the potential for resistance development and cross-resistance
      between different agents from this class. A-315675 is a novel influenza virus NA
      inhibitor that has potent enzyme activity and is highly active in cell culture
      against a variety of strains of influenza A and B viruses. To further assess the
      therapeutic potential of this compound, in vitro resistance studies have been
      conducted and a comparative assessment has been made relative to oseltamivir
      carboxylate. The development of viral resistance to A-315675 was studied by in
      vitro serial passage of influenza A/N9 virus strains grown in MDCK cells in the
      presence of increasing concentrations of A-315675. Parallel passaging experiments
      were conducted with oseltamivir carboxylate, the active form of a currently
      marketed oral agent for the treatment of influenza virus infections. Passage
      experiments with A-315675 identified a variant at passage 8 that was 60-fold less
      susceptible to the compound. Sequencing of the viral population identified an
      E119D mutation in the NA gene, but no mutations were observed in the
      hemagglutinin (HA) gene. However, by passage 10 (2.56 microM A-315675), two
      mutations (R233K, S339P) in the HA gene appeared in addition to the E119D
      mutation in the NA gene, resulting in a 310-fold-lower susceptibility to A
      315675. Further passaging at higher drug concentrations had no effect on the
      generation of further NA or HA mutations (20.5 microM A-315675). This P15 virus
      displayed 355-fold-lower susceptibility to A-315675 and >175-fold-lower
      susceptibility to zanamivir than did wild-type virus, but it retained a high
      degree of susceptibility to oseltamivir carboxylate. By comparison, virus
      variants recovered from passaging against oseltamivir carboxylate (passage 14)
      harbored an E119V mutation and displayed a 6,000-fold-lower susceptibility to
      oseltamivir carboxylate and a 175-fold-lower susceptibility to zanamivir than did
      wild-type virus. Interestingly, this mutant still retained susceptibility to A
      315675 (42-fold loss). This suggests that cross-resistance between A-315675- and
      oseltamivir carboxylate-selected variants in vitro is minimal.

PMID- 11991967
TI  - Envelope-induced cell transformation by ovine betaretroviruses.
AB  - Ovine betaretroviruses include Jaagsiekte sheep retrovirus (JSRV) and enzootic
      nasal tumor virus (ENTV). JSRV and ENTV represent a unique class of oncogenic
      retroviruses that induce tumors of the respiratory tract. JSRV and ENTV are
      highly related but induce different diseases. Expression of the JSRV envelope
      (Env) induces transformation of rodent fibroblasts in vitro and phosphorylation
      of Akt, a central player in the phosphatidylinositol 3-kinase (PI-3K)/Akt signal
      transduction pathway. However, little information is available on the molecular
      biology of ENTV. In this study, we initially assessed whether the ENTV Env has
      the same properties as the homologous JSRV protein. We performed entry and
      interference assays using retroviral vectors pseudotyped with either the JSRV or
      the ENTV Env and sheep choroid plexus cells, choroid plexus cells stably
      expressing the JSRV Env protein, human 293T cells, mouse NIH 3T3 cells, or NIH
      3T3 cells expressing human hyaluronidase 2 (HYAL2), the cellular receptor for
      JSRV. The results obtained indicated that ENTV and JSRV share the same receptor
      in sheep cells and that they can use human HYAL2 as a cellular receptor in mouse
      cells. The ENTV Env induces transformation of rodent fibroblasts in vitro. As
      with the JSRV Env, the tyrosine at position 590 is critical for ENTV Env-induced
      cell transformation, and Akt is phosphorylated in ENTV Env-transformed cells but
      not in the parental cell lines. Thus, ovine betaretroviruses share a common
      mechanism of cell transformation. We further investigated the relevance of Akt
      activation in cells transformed by ovine betaretroviruses. A PI-3K inhibitor
      blocked Akt phosphorylation in JSRV Env-transformed cells, suggesting a possible
      involvement of PI-3K in JSRV and ENTV Env-induced cell transformation. In
      addition, phosphorylated Akt was detected in a cell line derived from a lung
      tumor of a sheep with naturally occurring ovine pulmonary adenocarcinoma.

PMID- 11991968
TI  - Regulation of tumor necrosis factor alpha promoter by human parvovirus B19 NS1
      through activation of AP-1 and AP-2.
AB  - Human parvovirus B19 frequently causes acute and chronic arthritis in adults. The
      molecular mechanism of B19 arthritis, however, remains poorly understood. We
      previously showed that the transmission of B19 from rheumatoid synoviocytes to
      monocytic cells is associated with enhanced secretion of tumor necrosis factor
      alpha (TNF-alpha), which triggers inflammation, and interleukin-6. To determine
      the role of B19 in the production of TNF-alpha, we focused on the function of its
      nonstructural protein, NS1, and established monocytic U937 lines transduced with
      the NS1 gene under the control of an inducible promoter. Production of TNF-alpha
      mRNA and protein was elevated in a manner associated with NS1 expression.
      Reporter assays revealed that AP-1 and AP-2 motifs on the TNF-alpha promoter were
      responsible for NS1-mediated up-regulation. Electrophoretic mobility shift assay
      showed specific binding of nuclear proteins from NS1 gene-transduced cells with
      the AP-1 or AP-2 probe. Antibodies against transcription factors AP-1 and AP-2
      and anti-NS1 antibody inhibited the binding of nuclear proteins to the
      corresponding probes. These data indicate that NS1 up-regulates TNF-alpha
      transcription via activation of AP-1 and AP-2 in monocytic cells. The molecular
      mechanisms of NS1-mediated TNF-alpha expression would explain the pathogenesis of
      B19-associated inflammation.

PMID- 11991969
TI  - A fifteen-amino-acid TVB peptide serves as a minimal soluble receptor for
      subgroup B avian leukosis and sarcoma viruses.
AB  - The TVB receptor for subgroup B, D, and E avian sarcoma and leukosis viruses
      (ASLVs) is a tumor necrosis factor receptor-related protein that is most closely
      related to the TRAIL receptors. Here we show that the major subgroup B viral
      interaction determinants of TVB are contained within a linear 15-amino-acid
      peptide derived from the N-terminal region of the receptor. Moreover, this
      peptide was sufficient not only for binding to ASLV-B but also for activating
      viral entry into mammalian cells that lacked the cognate viral receptor. Peptide
      dependent viral entry was blocked in the presence of bafilomycin A1, indicating
      that virions can be trafficked to an acidic endosomal fusion compartment without
      the need for physical attachment of the viral receptor to a cellular membrane.

PMID- 11991970
TI  - Efficient integration of recombinant adeno-associated virus DNA vectors requires
      a p5-rep sequence in cis.
AB  - The initial aim of this study was to combine attributes of adeno-associated virus
      (AAV) and adenovirus (Ad) gene therapy vectors to generate an Ad-AAV hybrid
      vector allowing efficient site-specific integration with Ad vectors. In executing
      our experimental strategy, we found that, in addition to the known
      incompatibility of Rep expression and Ad growth, an equally large obstacle was
      presented by the inefficiency of the integration event when using traditional
      recombinant AAV (rAAV) vectors. This study has addressed both of these problems.
      We have shown that a first-generation Ad can be generated that expresses Rep
      proteins at levels consistent with those found in wild-type AAV (wtAAV)
      infections and that Rep-mediated AAV persistence can occur in the presence of
      first-generation Ad vectors. Our finding that traditional rAAV plasmid vectors
      lack integration potency compared to wtAAV plasmid constructs (10- to 100-fold
      differences) was unexpected but led to the discovery of a previously unidentified
      AAV integration enhancer sequence element which functions in cis to an AAV
      inverted terminal repeat-flanked target gene. rAAV constructs containing left-end
      AAV sequence, including the p5-rep promoter sequence, integrate efficiently in a
      site-specific manner. The identification of this novel AAV integration enhancer
      element is consistent with previous studies, which have indicated that a high
      frequency of wtAAV recombinant junction formation occurs in the vicinity of the
      p5 promoter, and recent studies have demonstrated a role for this region in AAV
      DNA replication. Understanding the contribution of this element to the mechanism
      of AAV integration will be critical to the use of AAV vectors for targeted gene
      transfer applications.

PMID- 11991971
TI  - Transduction of interphase cells by avian sarcoma virus.
AB  - It has been generally believed that oncoretroviruses are dependent on mitosis for
      efficient nuclear entry of viral DNA. We previously identified a nuclear
      localization signal in the integrase protein of an oncoretrovirus, avian sarcoma
      virus (ASV), suggesting an active import mechanism for the integrase-DNA complex
      (G. Kukolj, R. A. Katz, and A. M. Skalka, Gene 223:157-163, 1998). Here, we have
      evaluated the requirement for mitosis in nuclear import and integration of ASV
      DNA. Using a modified ASV encoding a murine leukemia virus amphotropic env gene
      and a green fluorescent protein (GFP) reporter gene, DNA nuclear import was
      measured in cell cycle-arrested avian (DF-1) as well as human (HeLa) and mouse
      cells. The results showed efficient accumulation of nuclear forms of ASV DNA in
      gamma-irradiation-arrested cells. Efficient transduction of a GFP reporter gene
      was also observed after infection of cells that were arrested with gamma
      irradiation, mitomycin C, nocodazole, or aphidicolin, confirming that nuclear
      import and integration of ASV DNA can occur in the absence of mitosis. By
      monitoring GFP expression in individual cells, we also obtained evidence for
      nuclear import of viral DNA during interphase in cycling cells. Lastly, we
      observed that ASV can transduce postmitotic mouse neurons. These results support
      an active nuclear import mechanism for the oncoretrovirus ASV and suggest that
      this mechanism can operate in both nondividing and dividing cells.

PMID- 11991972
TI  - Human immunodeficiency virus type 1 subtype C molecular phylogeny: consensus
      sequence for an AIDS vaccine design?
AB  - An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C)
      in the AIDS epidemic has been associated with a high prevalence of HIV-1C
      infection in the southern African countries and with an expanding epidemic in
      India and China. Understanding the molecular phylogeny and genetic diversity of
      HIV-1C viruses may be important for the design and evaluation of an HIV vaccine
      for ultimate use in the developing world. In this study we analyzed the
      phylogenetic relationships (i) between 73 non-recombinant HIV-1C near-full-length
      genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C
      consensus sequences that represent different geographic subsets; and (iii)
      between specific isolates and consensus sequences. Based on the phylogenetic
      analyses of 73 near-full-length genomes, 16 "lineages" (a term that is used
      hereafter for discussion purposes and does not imply taxonomic standing) were
      identified within HIV-1C. The lineages were supported by high bootstrap values in
      maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum
      likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean
      value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity
      of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to
      7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence
      were significantly lower than distances between samples within all HIV-1C
      proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid
      frequencies were presented (that of Gag is presented in this work; those of Pol,
      Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere
      [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm]). Additionally,
      in the promoter region three NF-kappa B sites (GGGRNNYYCC) were identified within
      the consensus sequences of the entire set or any subset of HIV-1C isolates. This
      study suggests that the consensus sequence approach could overcome the high
      genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly
      if the assumption that an HIV-1C antigen with a more extensive match to the
      circulating viruses is likely to be more efficacious is proven in efficacy
      trials.

PMID- 11991973
TI  - Rous sarcoma virus Gag protein-oligonucleotide interaction suggests a critical
      role for protein dimer formation in assembly.
AB  - The structural protein Gag is the only viral product required for retrovirus
      assembly. Purified Gag proteins or fragments of Gag are able in vitro to
      spontaneously form particles resembling immature virions, but this process
      requires nucleic acid, as well as the nucleocapsid domain of Gag. To examine the
      role of nucleic acid in the assembly in vitro, we used a purified, slightly
      truncated version of the Rous sarcoma virus Gag protein, Delta MBD Delta PR, and
      DNA oligonucleotides composed of the simple repeating sequence GT. Apparent
      binding constants were determined for oligonucleotides of different lengths, and
      from these values the binding site size of the protein on the DNA was calculated.
      The ability of the oligonucleotides to promote assembly in vitro was assessed
      with a quantitative assay based on electron microscopy. We found that excess zinc
      or magnesium ion inhibited the formation of virus-like particles without
      interfering with protein-DNA binding, implying that interaction with nucleic acid
      is necessary but not sufficient for assembly in vitro. The binding site size of
      the Delta MBD Delta PR protein, purified in the presence of EDTA to remove zinc
      ions at the two cysteine-histidine motifs, was estimated to be 11 nucleotides
      (nt). This value decreased to 8 nt when the protein was purified in the presence
      of low concentrations of zinc ions. The minimum length of DNA oligonucleotide
      that promoted efficient assembly in vitro was 22 nt for the zinc-free form of the
      protein and 16 nt for the zinc-bound form. To account for this striking 1:2 ratio
      between binding site size and oligonucleotide length requirement, we propose a
      model in which the role of nucleic acid in assembly is to promote formation of a
      species of Gag dimer, which itself is a critical intermediate in the
      polymerizaton of Gag to form the protein shell of the immature virion.

PMID- 11991974
TI  - Substitution in the murine nectin1 receptor of a single conserved amino acid at a
      position distal from the herpes simplex virus gD binding site confers high
      affinity binding to gD.
AB  - By analogy with its human nectin1 counterpart, murine nectin1 serves as a
      cellular receptor for the entry of herpes simplex virus (HSV) into murine cells.
      HSV entry mediated by either receptor is dependent on the viral glycoprotein D
      (gD). Whereas human nectin1 binds gD at high affinity and in a saturable manner,
      murine nectin1 binds gD in a barely detectable fashion, depending on the
      sensitivity of the assay. The immunoglobulin type V domain of murine nectin
      differs from its human counterpart in 11 amino acids. To identify the key
      residues responsible for the high-affinity binding of gD to human nectin1, we
      replaced each of the 11 divergent amino acids with the human counterparts singly
      or in groups in an incremental manner. Replacement in murine nectin1 of six amino
      acids that lie within the gD binding region of human nectin1 (previously mapped
      to residues 64 to 94, likely the CC'C" surface) increased the gD binding activity
      to a limited extent. In contrast, the single P138L substitution, which lies
      distal from the gD binding site, markedly increased gD binding. This
      substitution, when coupled with downstream substitutions, exerted the greatest
      effect. Three-dimensional modeling of the nectin1 V domain suggested that P138 in
      murine nectin1 might decrease the stability of the V domain by reducing the size
      of beta-strand G. The results support the notion that the overall structure of V
      nectin1 plays a pivotal role in its ability to bind HSV gD.

PMID- 11991975
TI  - Late assembly domain function can exhibit context dependence and involves
      ubiquitin residues implicated in endocytosis.
AB  - Retroviral Gag polyproteins contain regions that promote the separation of virus
      particles from the plasma membrane and from each other. These Gag regions are
      often referred to as late assembly (L) domains. The L domain of human
      immunodeficiency virus type 1 (HIV-1) is in the C-terminal p6(gag) domain and
      harbors an essential P(T/S)APP motif, whereas the L domains of oncoretroviruses
      are in the N-terminal half of the Gag precursor and have a PPXY core motif. We
      recently observed that L domains induce the ubiquitination of a minimal HIV-1 Gag
      construct and that point mutations which abolish L domain activity prevent Gag
      ubiquitination. In that study, a peptide from the Ebola virus L domain with
      overlapping P(T/S)APP and PPXY motifs showed exceptional activity in promoting
      Gag ubiquitination and the release of virus-like particles. We now show that a
      substitution which disrupts the PPXY motif but leaves the P(T/S)APP motif intact
      abolishes L domain activity in the minimal Gag context, but not in the context of
      a near full-length HIV-1 Gag precursor. Our results reveal that the P(T/S)APP
      motif does not function autonomously and indicate that the HIV-1 nucleocapsid-p1
      region, which is proximal to p6(gag), can cooperate with the conserved L domain
      core motif. We have also examined the effects of ubiquitin mutants on virus-like
      particle production, and the results indicate that residues required for the
      endocytosis function of ubiquitin are also involved in virus budding.

PMID- 11991976
TI  - Folding and dimerization of tick-borne encephalitis virus envelope proteins prM
      and E in the endoplasmic reticulum.
AB  - Flavivirus envelope proteins are synthesized as part of large polyproteins that
      are co- and posttranslationally cleaved into their individual chains. To
      investigate whether the interaction of neighboring proteins within the precursor
      protein is required to ensure proper maturation of the individual components, we
      have analyzed the folding of the flavivirus tick-borne encephalitis (TBE) virus
      envelope glycoproteins prM and E by using a recombinant plasmid expression system
      and virus-infected cells. When expressed in their polyprotein context, prM and E
      achieved their native folded structures with half-times of approximately 4 min
      for prM and about 15 min for E. They formed heterodimeric complexes within a few
      minutes after synthesis that were required for the final folding of E but not for
      that of prM. Heterodimers could also be formed in trans when these proteins were
      coexpressed from separate constructs. When expressed without prM, E could form
      disulfide bonds but did not express a specific conformational epitope and
      remained sensitive to reduction by dithiothreitol. This is consistent with a
      chaperone-like role for prM in the folding of E. PrM was able to achieve its
      native folded structure without coexpression of E, but signal sequence cleavage
      at the N terminus was delayed. Our results show that prM is an especially rapidly
      folding viral glycoprotein, that polyprotein cleavage and folding of the TBE
      virus envelope proteins occurs in a coordinated sequence of processing steps, and
      that proper and efficient maturation of prM and E can only be achieved by
      cosynthesis of these two proteins.

PMID- 11991977
TI  - Ambisense sendai viruses are inherently unstable but are useful to study viral
      RNA synthesis.
AB  - Ambisense Sendai virus (SeV) was prepared in order to study the control of viral
      RNA synthesis. In these studies, we found that the relative ratios of
      genomes/antigenomes formed during infection are largely determined by the
      relative strengths of the replication promoters, independent of the presence of a
      functional mRNA start site. We also found that the ability of the viral
      polymerase (vRdRP) to respond to an mRNA editing site requires prior
      (re)initiation at an mRNA start site, similar to the acquisition of vRdRP
      processivity in the absence of nascent chain coassembly. During these studies,
      the inherent instability of ambisense SeV upon passage in embryonated chicken
      eggs was noted and was found to be associated with a point mutation in the
      ambisense mRNA (ambi-mRNA) start site that severely limited its expression. Since
      the interferon (IFN)-induced antiviral state is mediated in part via double
      stranded RNA (dsRNA), the efficiency of the ambi-mRNA poly(A)/stop site was
      examined. This site was found to operate in a manner similar to that of other SeV
      mRNA poly(A)/stop sites, i.e., at approximately 95% efficiency. This modest level
      of vRdRP read-through is apparently tolerable for natural SeV because the
      potential to form dsRNA during infection remains limited. However, when mRNAs are
      expressed from ambisense SeV antigenomes, vRdRP read-through of the ambi-mRNA
      poly(A)/stop site creates a capped transcript that can potentially extend the
      entire length of the antigenome, since there are no further poly(A)/stop sites
      here. In support of this hypothesis, loss of ambi-mRNA expression during passage
      of ambisense SeV stocks in eggs is also characterized by conversion of virus that
      grows poorly in IFN-sensitive cultures and is relatively IFN sensitive to virus
      that grows well even in IFN-pretreated cells that restrict vesicular stomatitis
      virus replication, i.e., the wild-type SeV phenotype. The selection of mutants
      unable to express ambi-mRNA on passage in chicken eggs is presumably due to
      increased levels of dsRNA during infection. How natural ambisense viruses may
      deal with this dilemma is discussed.

PMID- 11991978
TI  - Analysis of an Autographa californica multicapsid nucleopolyhedrovirus lef-6-null
      virus: LEF-6 is not essential for viral replication but appears to accelerate
      late gene transcription.
AB  - The Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) lef-6 gene
      was previously shown to be necessary for optimal transcription from an AcMNPV
      late promoter in transient late expression assays. In the present study, we
      examined the expression and cellular localization of lef-6 during the AcMNPV
      infection cycle and generated a lef-6-null virus for studies of the role of lef-6
      in the infection cycle. Transcription of lef-6 was detected from 4 to 48 h
      postinfection, and the LEF-6 protein was identified in dense regions of infected
      cell nuclei, a finding consistent with its potential role as a late transcription
      factor. To examine lef-6 in the context of the AcMNPV infection cycle, we deleted
      the lef-6 gene from an AcMNPV genome propagated as an infectious BACmid in
      Escherichia coli. Unexpectedly, the resulting AcMNPV lef-6-null BACmid
      (vAc(lef6KO)) was able to propagate in cell culture, although virus yields were
      substantially reduced. Thus, the lef-6 gene is not essential for viral
      replication in Sf9 cells. Two "repair" AcMNPV BACmids (vAc(lef6KO-REP-P) and
      vAc(lef6KO-REP-ie1P)) were generated by transposition of the lef-6 gene into the
      polyhedrin locus of the vAc(lef6KO) BACmid. Virus yields from the two repair
      viruses were similar to those from wild-type AcMNPV or a control (BACmid-derived)
      virus. The lef-6-null BACmid (vAc(lef6KO)) was further examined to determine
      whether the deletion of lef-6 affected DNA replication or late gene transcription
      in the context of an infection. The lef-6 deletion did not appear to affect viral
      DNA replication. Using Northern blot analysis, we found that although early
      transcription was apparently unaffected, both late and very late transcription
      were delayed in cells infected with the lef-6-null BACmid. This phenotype was
      rescued in viruses containing the lef-6 gene reinserted into the polyhedrin
      locus. Thus, the lef-6 gene was not essential for either viral DNA replication or
      late gene transcription, but the absence of lef-6 resulted in a substantial delay
      in the onset of late transcription. Therefore, lef-6 appears to accelerate the
      infection cycle of AcMNPV.

PMID- 11991979
TI  - Inhibition of tumor necrosis factor alpha-induced NF-kappa B activation by the
      adenovirus E3-10.4/14.5K complex.
AB  - Recombinant adenoviruses (Ads) are useful tools in gene transfer because they are
      able to infect a wide variety of tissues and cell types and do not require a
      replicating target cell. However, transgene expression is only transient due to
      host innate and acquired immune responses to the virus. Most recombinant Ads have
      deletions of early region 3 (E3) genes, allowing more space for insertion of the
      transgene. Although the E3 region is not necessary for infection, it has been
      observed that these "nonessential" genes have immunomodulatory properties. We
      demonstrate here that the E3 region of Ad inhibits the activation of NF-kappa B
      induced by tumor necrosis factor alpha (TNF-alpha) and interleukin-1. Ad E3 is
      able to prevent NF-kappa B from entering the nucleus, where it is normally
      active. Ad E3 also appears to function by preventing the activation of the kinase
      complex, IKK, which is responsible for phosphorylation of I kappa B that retains
      NF-kappa B in the cytoplasm in an inactive state. The prevention of NF-kappa B
      activation has been mapped to a complex of two of the seven E3 products, E3-10.4K
      and E3-14.5K (RID alpha/beta). These and other studies indicate that, by using Ad
      vectors containing the E3 region, it may be possible to reduce the harmful
      proinflammatory effects of TNF-alpha and other cytokines that compromise the use
      of Ad gene therapy vectors in vivo.

PMID- 11991980
TI  - Kaposi's sarcoma-associated herpesvirus K3 utilizes the ubiquitin-proteasome
      system in routing class major histocompatibility complexes to late endocytic
      compartments.
AB  - Human herpesvirus 8 (HHV8) downregulates major histocompatibility complex (MHC)
      class I complexes from the plasma membrane via two of its genes, K3 and K5. The N
      termini of K3 and K5 contain a plant homeodomain (PHD) predicted to be
      structurally similar to RING domains found in E3 ubiquitin ligases. In view of
      the importance of the ubiquitin-proteasome system in sorting within the endocytic
      pathway, we analyzed its role in downregulation of MHC class I complexes in cells
      expressing K3. Proteasome inhibitors as well as cysteine and aspartyl protease
      inhibitors stabilize MHC class I complexes in cells expressing K3. However,
      proteasome inhibitors differentially affect sorting of MHC class I complexes
      within the endocytic pathway and prevent their delivery to a dense endosomal
      compartment. In this compartment, the cytoplasmic tail of MHC class I complexes
      is cleaved by cysteine proteases. The complex is then cleaved within the plane of
      the membrane by an aspartyl protease, resulting in a soluble MHC class I fragment
      composed of the lumenal domain of the heavy chain, beta(2)-microglobulin
      (beta(2)m), and peptide. We conclude that K3 not only directs internalization,
      but also targets MHC class I complexes to a dense endocytic compartment on the
      way to lysosomes in a ubiquitin-proteasome-dependent manner.

PMID- 11991982
TI  - Isolation and analysis of retroviral integration targets by solo long terminal
      repeat inverse PCR.
AB  - Upon retroviral infection, the genomic RNA is reverse transcribed to make
      proviral DNA, which is then integrated into the host chromosome. Although the
      viral elements required for successful integration have been extensively
      characterized, little is known about the host DNA structure constituting
      preferred targets for proviral integration. In order to elucidate the mechanism
      for the target selection, comparison of host DNA sequences at proviral
      integration sites may be useful. To achieve simultaneous analysis of the upstream
      and downstream host DNA sequences flanking each proviral integration site, a
      Moloney murine leukemia virus-based retroviral vector was designed so that its
      integrated provirus could be removed by Cre-loxP homologous recombination,
      leaving a solo long terminal repeat (LTR). Taking advantage of the solo LTR,
      inverse PCR was carried out to amplify both the upstream and downstream cellular
      flanking DNA. The method called solo LTR inverse PCR, or SLIP, proved useful for
      simultaneously cloning the upstream and downstream flanking sequences of
      individual proviral integration sites from the polyclonal population of cells
      harboring provirus at different chromosomal sites. By the SLIP method, nucleotide
      sequences corresponding to 38 independent proviral integration targets were
      determined and, interestingly, atypical virus-host DNA junction structures were
      found in more than 20% of the cases. Characterization of retroviral integration
      sites using the SLIP method may provide useful insights into the mechanism for
      proviral integration and its target selection.

PMID- 11991981
TI  - Transcriptional profiling of interferon regulatory factor 3 target genes: direct
      involvement in the regulation of interferon-stimulated genes.
AB  - Ubiquitously expressed interferon regulatory factor 3 (IRF-3) is directly
      activated after virus infection and functions as a key activator of the immediate
      early alpha/beta interferon (IFN) genes, as well as the RANTES chemokine gene. In
      the present study, a tetracycline-inducible expression system expressing a
      constitutively active form of IRF-3 (IRF-3 5D) was combined with DNA microarray
      analysis to identify target genes regulated by IRF-3. Changes in mRNA expression
      profiles of 8,556 genes were monitored after Tet-inducible expression of IRF-3
      5D. Among the genes upregulated by IRF-3 were transcripts for several known IFN
      stimulated genes (ISGs). Subsequent analysis revealed that IRF-3 directly induced
      the expression of ISG56 in an IFN-independent manner through the IFN-stimulated
      responsive elements (ISREs) of the ISG56 promoter. These results demonstrate
      that, in addition to its role in the formation of a functional immediate-early
      IFN-beta enhanceosome, IRF-3 is able to discriminate among ISRE-containing genes
      involved in the establishment of the antiviral state as a direct response to
      virus infection.

PMID- 11991983
TI  - Characterizing and mapping porcine endogenous retroviruses in Westran pigs.
AB  - Since porcine endogenous retroviruses (PERVs) can infect cultured human cells,
      they are a potential hazard to xenotransplantation. For this reason, endogenous
      retroviruses from the Westran (Westmead Hospital transplantation) inbred line of
      pigs were analyzed by using consensus primers for the type A and type B viruses
      to amplify 1.8-kb envelope gene fragments. After preliminary analysis with
      restriction enzymes KpnI and MboI, 31 clones were sequenced. Between types A and
      B, five recombinant clones were identified. Fifty-five percent of clones (17 of
      31) had premature stop codons within the envelope protein-encoding region.
      Endogenous retroviruses in Westran pigs were physically mapped by fluorescence in
      situ hybridization (FISH) using PERV-A and PERV-B envelope clones as probes to
      identify at least 32 integration sites (19 PERV-A sites and 13 PERV-B sites). The
      chromosomal sites of integration in the Westran strain are quite different from
      those in the European Large White pig. The recombinant clones suggest that
      defective PERVs could become infective through recombination and further that
      PERVs might recombine with human endogenous retroviruses in xenotransplants.

PMID- 11991984
TI  - Overcoming the phage replication threshold: a mathematical model with
      implications for phage therapy.
AB  - Prior observations of phage-host systems in vitro have led to the conclusion that
      susceptible host cell populations must reach a critical density before phage
      replication can occur. Such a replication threshold density would have broad
      implications for the therapeutic use of phage. In this report, we demonstrate
      experimentally that no such replication threshold exists and explain the previous
      data used to support the existence of the threshold in terms of a classical model
      of the kinetics of colloidal particle interactions in solution. This result leads
      us to conclude that the frequently used measure of multiplicity of infection
      (MOI), computed as the ratio of the number of phage to the number of cells, is
      generally inappropriate for situations in which cell concentrations are less than
      10(7)/ml. In its place, we propose an alternative measure, MOI(actual), that
      takes into account the cell concentration and adsorption time. Properties of this
      function are elucidated that explain the demonstrated usefulness of MOI at high
      cell densities, as well as some unexpected consequences at low concentrations. In
      addition, the concept of MOI(actual) allows us to write simple formulas for
      computing practical quantities, such as the number of phage sufficient to infect
      99.99% of host cells at arbitrary concentrations.

PMID- 11991985
TI  - Expression of human immunodeficiency virus type 1 gp120 from herpes simplex virus
      type 1-derived amplicons results in potent, specific, and durable cellular and
      humoral immune responses.
AB  - Herpes simplex virus type 1 (HSV-1) infects a wide range of cells, including
      dendritic cells. Consequently, HSV-1 vectors may be capable of eliciting strong
      immune responses to vectored antigens. To test this hypothesis, an HSV-1 amplicon
      plasmid encoding human immunodeficiency virus type 1 gp120 was constructed, and
      murine immune responses to helper virus-free amplicon preparations derived from
      this construct were evaluated. Initial studies revealed that a single
      intramuscular (i.m.) injection of 10(6) infectious units (i.u.) of HSV:gp120
      amplicon particles (HSV:gp120) elicited Env-specific cellular and humoral immune
      responses. A potent, CD8(+)-T-cell-mediated response to an H-2D(d)-restricted
      peptide from gp120 (RGPGRAFVTI) was measured by a gamma interferon ELISPOT and
      was confirmed by standard cytotoxic-T-lymphocyte assays. Immunoglobulin G enzyme
      linked immunosorbent assay analysis showed the induction of a strong, Env
      specific antibody response. An i.m. or an intradermal administration of HSV:gp120
      at the tail base elicited a more potent cellular immune response than did an
      intraperitoneal (i.p.) inoculation, although an i.p. introduction generated a
      stronger humoral response. The immune response to HSV:gp120 was durable, with
      robust cellular and humoral responses persisting at 171 days after a single 10(6)
      i.u. inoculation. The immune response to HSV:gp120 was also found to be dose
      dependent: as few as 10(4) i.u. elicited a strong T-cell response. Finally,
      HSV:gp120 elicited significant Env-specific cellular immune responses even in
      animals that had been previously infected with wild-type HSV-1. Taken together,
      these data strongly support the use of helper-free HSV-1 amplicon particles as
      vaccine delivery vectors.

PMID- 11991986
TI  - An NF-kappa B-dependent survival pathway protects against cell death induced by
      TVB receptors for avian leukosis viruses.
AB  - TVB receptors are death receptors of the tumor necrosis factor receptor (TNFR)
      family and serve as cellular receptors for cytopathic subgroups B and D and
      noncytopathic subgroup E of the avian leukosis viruses (ALVs). Although TVB is
      essential for ALV-B-mediated cell death, binding of the ALV-B envelope protein to
      its cognate receptor TVB activates cell death only in the presence of protein
      biosynthesis inhibitors, which presumably block the expression of protective
      factors. In the case of TNFR-1, the main antiapoptotic pathway depends upon
      nuclear factor kappa B (NF-kappa B)-activated survival factors. Here we show that
      overexpression of TVB receptors in human 293 cells activates NF-kappa B via a
      mechanism involving the cytoplasmic death domains of these receptors. NF-kappa B
      is also activated upon binding of a soluble ALV-B or ALV-E surface envelope
      immunoglobulin fusion protein to the cognate TVB receptors and by ALV-B infection
      of a chicken embryo fibroblast cell line (DF1). Importantly, the cycloheximide
      requirement for TVB-dependent cell death was overcome by the expression of a
      transdominant form of I kappa B-alpha, and downregulation of NF-kappa B by the
      immunomodulator pyrrolidinedithiocarbamate enhanced the cytopathogenicity of ALV
      B. These results demonstrate that TVB receptors trigger NF-kappa B-dependent gene
      expression and that NF-kappa B-regulated survival factors can protect against
      virus-induced cell death.

PMID- 11991987
TI  - Increased production of interleukin-8 in primary human monocytes and in human
      epithelial and endothelial cell lines after dengue virus challenge.
AB  - The more severe form of dengue virus infection, dengue hemorrhagic fever, is
      characterized by plasma leakage and derangements in hemostasis. As elevated
      interleukin-8 (IL-8) levels have been observed in sera from patients with more
      severe disease manifestations, a study was initiated to look at the effect of
      dengue virus infection in vitro on proinflammatory cytokine secretion and
      expression. A significant increase in IL-8 levels in the culture supernatant of
      primary human monocytes infected with dengue 2 virus (D2V) New Guinea C (NGC) was
      found by enzyme-linked immunosorbent assay. Additionally, by reverse
      transcriptase PCR, the mRNA was also augmented. Among the proinflammatory
      cytokines and their mRNAs measured (IL-6, IL-1 beta, IL-8, and tumor necrosis
      factor alpha), IL-8 showed the greatest change following D2V infection.
      Similarly, two cell lines, 293T (a human epithelial cell line) and ECV304 (an
      endothelial cell line), were permissive to D2V NGC and responded to the infection
      by increasing the synthesis of IL-8. Nuclear factor kappa B (NF-kappa B) and
      nuclear factor IL-6 (NFIL-6) are primary mediators of IL-8 expression. We studied
      the transcriptional regulation of IL-8 in the ECV304 and 293T cell lines and
      found that the induction of IL-8 gene expression involved the activation of NF
      kappa B (P = 0.001) and, to a lesser extent, the activation of NFIL-6 in ECV304
      cells only. We next observed by the chromatin immunoprecipitation procedure in
      vivo acetylation of core histones bound to the IL-8 promoter after D2V infection.
      IL-8 produced by infected monocytes and also IL-8 that may be produced by
      endothelial or other epithelial cells is associated with the hyperacetylation of
      histones bound to the IL-8 promoter in addition to the activation of
      transcription by NF-kappa B. We hypothesize that the overall increase in IL-8
      synthesis observed in this in vitro study may play a role in the pathogenesis of
      the plasma leakage seen in dengue hemorrhagic fever and dengue shock syndrome.

PMID- 11991988
TI  - The acidic activation domain of the baculovirus transactivator IE1 contains a
      virus-specific domain essential for DNA replication.
AB  - IE1 is a potent transcriptional transactivator of the baculovirus Orgyia
      pseudotsugata multiple nucleopolyhedrovirus (OpMNPV) and has been shown to be
      essential for viral DNA replication. IE1 contains an acidic activation domain
      (AAD) at the N terminus that is essential for transcriptional transactivation,
      but its role in viral DNA replication is unknown. In this study the role of the
      IE1 AAD in DNA replication is investigated. We have determined that deletion of
      the AAD eliminates the ability of IE1 to support DNA replication, showing that
      the AAD is essential for DNA replication as well as transcriptional
      transactivation. Replacement of the AAD with the archetype domain from
      herpesvirus VP16 and the evolutionarily related domain from Autographa
      californica MNPV (AcMNPV) IE1 produces chimeric proteins that are potent
      transactivators. Surprisingly, however, these chimeric proteins were unable to
      support DNA replication, indicating that there is a host- or virus-specific
      replication subdomain in the AAD that was not functionally replaced by the VP16
      or AcMNPV AAD. Using N- and C-terminal deletion mutants, the region of the AAD
      that was essential for DNA replication was mapped to amino acids 1 to 65. AAD
      deletion mutants also showed that an IE1 that is functional for transcriptional
      transactivation is not required for viral DNA replication. The IE1 AAD therefore
      contains an essential replication domain that is separable from the
      transcriptional activation domains. Our results suggest that IE1 specifically
      interacts with a component of the viral replication complex, supporting the view
      that it acts as a nucleating factor by binding to the viral replication origins.

PMID- 11991989
TI  - Pivotal role of the non-hr origin of DNA replication in the genesis of defective
      interfering baculoviruses.
AB  - The generation of deletion mutants, including defective interfering viruses, upon
      serial passage of Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) in
      insect cell culture has been studied. Sequences containing the non-homologous
      region origin of DNA replication (non-hr ori) became hypermolar in intracellular
      viral DNA within 10 passages in Se301 insect cells, concurrent with a dramatic
      drop in budded virus and polyhedron production. These predominant non-hr ori
      containing sequences accumulated in larger concatenated forms and were generated
      de novo as demonstrated by their appearance and accumulation upon infection with
      a genetically homogeneous bacterial clone of SeMNPV (bacmid). Sequences were
      identified at the junctions of the non-hr ori units within the concatemers, which
      may be potentially involved in recombination events. Deletion of the SeMNPV non
      hr ori using RecE/RecT-mediated homologous ET recombination in Escherichia coli
      resulted in a recombinant bacmid with strongly enhanced stability of virus and
      polyhedron production upon serial passage in insect cells. This suggests that the
      accumulation of non-hr oris upon passage is due to the replication advantage of
      these sequences. The non-hr ori deletion mutant SeMNPV bacmid can be exploited as
      a stable eukaryotic heterologous protein expression vector in insect cells.

PMID- 11991990
TI  - Protein kinase C-independent activation of the Epstein-Barr virus lytic cycle.
AB  - The protein kinase C (PKC) pathway has been considered to be essential for
      activation of latent Epstein-Barr virus (EBV) into the lytic cycle. The phorbol
      ester tetradecanoyl phorbol acetate (TPA), a PKC agonist, is one of the best
      understood activators of EBV lytic replication. Zp, the promoter of the EBV
      immediate-early gene BZLF1, whose product, ZEBRA, drives the lytic cycle,
      contains several phorbol ester response elements. We investigated the role of the
      PKC pathway in lytic cycle activation in prototype cell lines that differed
      dramatically in their response to inducing agents. We determined whether PKC was
      involved in lytic cycle induction by histone deacetylase (HDAC) inhibitors.
      Consistent with prevailing views, B95-8 cells were activated into the lytic cycle
      by the phorbol ester TPA, via a PKC-dependent mechanism. B95-8 was not inducible
      by HDAC inhibitors such as n-butyrate and trichostatin A (TSA).
      Bisindolylmaleimide I, a selective PKC inhibitor, blocked lytic cycle activation
      in B95-8 cells in response to TPA. In marked contrast, in HH514-16 cells, the
      immediate-early promoters Zp and Rp were simultaneously activated by the HDAC
      inhibitors; TPA by itself failed to activate lytic gene expression. Inhibition of
      PKC activity by bisindolylmaleimide I did not block lytic cycle activation in
      HH514-16 cells by n-butyrate or TSA. In an extensive exploration of the mechanism
      underlying these different responses we found that the variable role of the PKC
      pathway in the two cell lines could not be accounted for by significant
      polymorphisms in the promoters of the immediate-early genes, by differences in
      the start sites of immediate-early gene transcription, or by differences in the
      nucleosomal organization of EBV DNA in the region of Zp or Rp. While B95-8 cells
      contained more total PKC activity than did HH514-16 cells in an in vitro assay,
      another EBV-transformed marmoset lymphoblastoid cell line, FF41, in which the
      lytic cycle was not inducible by TPA, contained comparably high levels of PKC
      activity. Moreover, two marmoset lymphoblastoid cells lines in which the lytic
      cycle could not be triggered by TPA maintained the same profile of EBV latency
      proteins as B95-8 cells. Thus, the profile of EBV latency proteins did not
      account for susceptibility to induction by PKC agonists. PKC activation is
      neither obligatory nor sufficient for the switch between latency and lytic cycle
      gene expression of EBV in many cell backgrounds. Lytic cycle induction by HDAC
      inhibitors proceeds by a PKC-independent mechanism.

PMID- 11991991
TI  - Identification of amino acid residues of gp130 signal transducer and gp80 alpha
      receptor subunit that are involved in ligand binding and signaling by human
      herpesvirus 8-encoded interleukin-6.
AB  - Human herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the gp130
      signal transducer but is not dependent on the IL-6 receptor alpha subunit (IL-6R,
      gp80) that is required for signaling by endogenous IL-6 proteins; however, IL-6R
      can enhance vIL-6 activity and can enable signaling through a gp130 variant,
      gp130.PM5, that is itself unable to support vIL-6 signaling. These findings
      suggest that the vIL-6-gp130 interactions are qualitatively different from those
      of human IL-6 (hIL-6) and that vIL-6 signaling may be more promiscuous than that
      of hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To examine
      the receptor binding requirements of vIL-6, we have undertaken mutational
      analyses of regions of gp130 and IL-6R potentially involved in interactions with
      ligand or in functional complex formation and used these variants in functional,
      ligand-binding, and receptor dimerization assays. The data presented identify
      positions within two interstrand loops of the gp130 cytokine-receptor homology
      domain that are important for vIL-6 signaling and vIL-6-induced receptor
      dimerization and show that vIL-6, like hIL-6, can form complexes with IL-6R and
      gp130 but that the roles of putative cytokine-binding residues of IL-6R in ligand
      induced functional complex formation are qualitatively different in the case of
      vIL-6 and hIL-6.

PMID- 11991992
TI  - Complete, long-lasting protection against lethal infectious bursal disease virus
      challenge by a single vaccination with an avian herpesvirus vector expressing VP2
      antigens.
AB  - Marek's disease herpesvirus is a vaccine vector of great promise for chickens;
      however, complete protection against foreign infectious diseases has not been
      achieved. In this study, two herpesvirus of turkey recombinants (rHVTs)
      expressing large amounts of infectious bursal disease virus (IBDV) VP2 antigen
      under the control of a human cytomegalovirus (CMV) promoter or CMV/beta-actin
      chimera promoter (Pec promoter) (rHVT-cmvVP2 and rHVT-pecVP2) were constructed.
      rHVT-pecVP2, which expressed the VP2 antigen approximately four times more than
      did rHVT-cmvVP2 in vitro, induced complete protection against a lethal IBDV
      challenge in chickens, whereas rHVT-cmvVP2 induced 58% protection. All of the
      chickens vaccinated with rHVT-pecVP2 had a protective level of antibodies to the
      VP2 antigen at the time of challenge, whereas only 42 and 67% of chickens
      vaccinated with rHVT-cmvVP2 or the conventional live IBDV vaccine, respectively,
      had the antibodies. The antibody level of chickens vaccinated with rHVT-pecVP2
      increased for 16 weeks, and the peak antibody level persisted throughout the
      experiment. The serum antibody titer at 30 weeks of age was about 20 or 65 times
      higher than that of chickens vaccinated with rHVT-cmvVP2 or the conventional live
      vaccine, respectively. rHVT-pecVP2, isolated consistently for 30 weeks from the
      vaccinated chickens, expressed the VP2 antigen after cultivation, and neither
      nucleotide mutations nor deletion in the VP2 gene was found. These results
      demonstrate that the amount of VP2 antigen expressed in the HVT vector was
      correlated with the vaccine efficacy against lethal IBDV challenge, and complete
      protective immunity that is likely to persist for the life of the chickens was
      induced.

PMID- 11991993
TI  - Cytokine-sensitive replication of hepatitis B virus in immortalized mouse
      hepatocyte cultures.
AB  - We have previously shown that alpha/beta interferon (IFN-alpha/beta) and gamma
      interferon (IFN-gamma) inhibit hepatitis B virus (HBV) replication by eliminating
      pregenomic RNA containing viral capsids from the hepatocyte. We have also shown
      that HBV-specific cytotoxic T lymphocytes that induce IFN-gamma and tumor
      necrosis factor alpha (TNF-alpha) in the liver can inhibit HBV gene expression by
      destabilizing preformed viral mRNA. In order to further study the antiviral
      activity of IFN-alpha/beta, IFN-gamma, and TNF-alpha at the molecular level, we
      sought to reproduce these observations in an in vitro system. Accordingly,
      hepatocytes were derived from the livers of HBV-transgenic mice that also
      expressed the constitutively active cytoplasmic domain of the human hepatocyte
      growth factor receptor (c-Met). Here, we show that the resultant well
      differentiated, continuous hepatocyte cell lines (HBV-Met) replicate HBV and that
      viral replication in these cells is efficiently controlled by IFN-alpha/beta or
      IFN-gamma, which eliminate pregenomic RNA-containing capsids from the cells as
      they do in the liver. Furthermore, we demonstrate that IFN-gamma, but not IFN
      alpha/beta, is capable of inhibiting HBV gene expression in this system,
      especially when it acts synergistically with TNF-alpha. These cells should
      facilitate the analysis of the intracellular signaling pathways and effector
      mechanisms responsible for these antiviral effects.

PMID- 11991994
TI  - Respiratory syncytial virus infection of human airway epithelial cells is
      polarized, specific to ciliated cells, and without obvious cytopathology.
AB  - Gene therapy for cystic fibrosis (CF) lung disease requires efficient gene
      transfer to airway epithelial cells after intralumenal delivery. Most gene
      transfer vectors so far tested have not provided the efficiency required.
      Although human respiratory syncytial virus (RSV), a common respiratory virus, is
      known to infect the respiratory epithelium, the mechanism of infection and the
      epithelial cell type targeted by RSV have not been determined. We have utilized
      human primary airway epithelial cell cultures that generate a well-differentiated
      pseudostratified mucociliary epithelium to investigate whether RSV infects airway
      epithelium via the lumenal (apical) surface. A recombinant RSV expressing green
      fluorescent protein (rgRSV) infected epithelial cell cultures with high gene
      transfer efficiency when applied to the apical surface but not after basolateral
      inoculation. Analyses of the cell types infected by RSV revealed that lumenal
      columnar cells, specifically ciliated epithelial cells, were targeted by RSV and
      that cultures became susceptible to infection as they differentiated into a
      ciliated phenotype. In addition to infection of ciliated cells via the apical
      membrane, RSV was shed exclusively from the apical surface and spread to
      neighboring ciliated cells by the motion of the cilial beat. Gross histological
      examination of cultures infected with RSV revealed no evidence of obvious
      cytopathology, suggesting that RSV infection in the absence of an immune response
      can be tolerated for >3 months. Therefore, rgRSV efficiently transduced the
      airway epithelium via the lumenal surface and specifically targeted ciliated
      airway epithelial cells. Since rgRSV appears to breach the lumenal barriers
      encountered by other gene transfer vectors in the airway, this virus may be a
      good candidate for the development of a gene transfer vector for CF lung disease.

PMID- 11991995
TI  - Formation of a human immunodeficiency virus type 1 core of optimal stability is
      crucial for viral replication.
AB  - Virions of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses
      contain conical cores consisting of a protein shell composed of the viral capsid
      protein (CA) surrounding an internal viral ribonucleoprotein complex. Although
      genetic studies have implicated CA in both early and late stages of the virus
      replication cycle, the mechanism of core disassembly following penetration of
      target cells remains undefined. Using quantitative assays for analyzing HIV-1
      core stability in vitro, we identified point mutations in CA that either reduce
      or increase the stability of the HIV-1 core without impairing conical core
      formation in virions. Alterations in core stability resulted in severely
      attenuated HIV-1 replication and impaired reverse transcription in target cells
      with only minimal effects on viral DNA synthesis in permeabilized virions in
      vitro. We conclude that formation of a viral core of optimal stability is a
      prerequisite for efficient HIV-1 infection and suggest that disassembly of the
      HIV-1 core is a regulated step in infection that may be an attractive target for
      pharmacologic intervention.

PMID- 11991996
TI  - Eukaryotic elongation factor 1A interacts with the upstream pseudoknot domain in
      the 3' untranslated region of tobacco mosaic virus RNA.
AB  - The genomic RNA of tobacco mosaic virus (TMV), like that of other positive-strand
      RNA viruses, acts as a template for both translation and replication. The highly
      structured 3' untranslated region (UTR) of TMV RNAs plays an important role in
      both processes; it is not polyadenylated but ends with a tRNA-like structure
      (TLS) preceded by a conserved upstream pseudoknot domain (UPD). The TLS of
      tobamoviral RNAs can be specifically aminoacylated and, in this state, can
      interact with eukaryotic elongation factor 1A (eEF1A)/GTP with high affinity.
      Using a UV cross-linking assay, we detected another specific binding site for
      eEF1A/GTP, within the UPDs of TMV and crucifer-infecting tobamovirus (crTMV),
      that does not require aminoacylation. A mutational analysis revealed that UPD
      pseudoknot conformation and some conserved primary sequence elements are required
      for this interaction. Its possible role in the regulation of tobamovirus gene
      expression and replication is discussed.

PMID- 11991997
TI  - Hepatic DR5 induces apoptosis and limits adenovirus gene therapy product
      expression in the liver.
AB  - A major limitation of adenovirus (Ad) gene therapy product expression in the
      liver is subsequent elimination of the hepatocytes expressing the gene therapy
      product. This elimination is caused by both necrosis and apoptosis related to the
      innate and cell-mediated immune response to the Ad. Apoptosis of hepatocytes can
      be induced by the innate immune response by signaling through death domain
      receptors on hepatocytes including the tumor necrosis factor alpha (TNF-alpha)
      receptor (TNFR), Fas, and death domain receptors DR4 and DR5. We have previously
      shown that blocking signaling through TNFR enhances and prolongs gene therapy
      product expression in the liver. In the present study, we constructed an Ad that
      produces a soluble DR5-Fc (AdsDR5), which is capable of neutralizing TNF-related
      apoptosis-inducing ligand (TRAIL). AdsDR5 prevents TRAIL-mediated apoptosis of
      CD3-activated T cells and decreases hepatocyte apoptosis after AdCMVLacZ
      administration and enhances the level and duration of lacZ transgene expression
      in the liver. In addition to blocking TRAIL and directly inhibiting apoptosis,
      AdsDR5 decreases production of gamma interferon (IFN-gamma) and TNF-alpha and
      decreases NK cell activation, all of which limit Ad-mediated transgene expression
      in the liver. These results indicate that (i) AdsDR5 produces a DR5-Fc capable of
      neutralizing TRAIL, (ii) AdsDR5 can reduce activation of NK cells and reduce
      induction of IFN-gamma and TNF-alpha after Ad administration, and (iii)
      administration of AdsDR5 can enhance Ad gene therapy in the liver.

PMID- 11991998
TI  - Langat flavivirus protease NS3 binds caspase-8 and induces apoptosis.
AB  - The flavivirus NS3 protein plays an important role in the cleavage and processing
      of the viral polyprotein and in the synthesis of the viral RNA. NS3 recruits NS2B
      and NS5 proteins to form complexes possessing protease and replicase activities
      through protease and nucleoside triphosphatase/helicase domains. We have found
      that NS3 also induces apoptosis. Expression of the Langat (LGT) virus NS3 protein
      resulted in a cleavage of cellular DNA and reduced the viability of cells.
      Coexpression of NS3 with apoptotic inhibitors (CrmA and P35) and addition of
      caspase peptide substrates (Z-VAD-FMK and Z-IETD-FMK) to NS3-transfected cells
      blocked NS3-induced apoptosis. In cotransfection experiments, NS3 bound to
      caspase-8 and enhanced caspase-8-mediated apoptosis. NS3 and caspase-8
      colocalized in the cytoplasm of transfected cells. Deletion analysis demonstrated
      that at least two regions of NS3 contribute to its apoptotic activities. The
      protease and helicase domains are each able to bind to caspase-8, while the
      protease domain alone induces apoptosis. The protease domain and tetrahelix
      region of the helicase domain are required for NS3 to augment caspase-8-mediated
      apoptosis. Thus, the LGT virus NS3 protein is a multifunctional protein that
      binds to caspase-8 and induces apoptosis.

PMID- 11991999
TI  - Preexisting immunity to adenovirus in rhesus monkeys fails to prevent vector
      induced toxicity.
AB  - In an earlier study we evaluated innate immune responses to a first-generation
      adenoviral vector infused into the portal vein of rhesus monkeys who had never
      been exposed to adenovirus previously. In these animals, the systemic
      administration of E1/E3-deleted adenoviral vectors resulted in immediate
      activation of innate immunity and serious toxicity caused by targeting of vector
      to antigen-presenting cells and systemic inflammation. We analyze here how these
      responses are affected by vector-specific preexisting immunity that was induced
      by intramuscular immunization 6 months prior to evaluation. Our results show that
      preexposure to the vector substantially diminishes the transgene expression in
      most tissues but has little effect on gene transfer. Significantly,
      preimmunization does not eliminate systemic vector-induced toxicity. These
      conclusions are based on the presence of clinical features of coagulopathy and
      elevated levels of proinflammatory cytokine interleukin-6 in the serum of animals
      treated with vector after intramuscular immunization. Furthermore, preexisting
      immunity appears to induce a vector-specific inhibitory effect on erythroid
      progenitor development in the bone marrow that is not found when naive animals
      are challenged with vector.

PMID- 11992000
TI  - Measles virus spreads in rat hippocampal neurons by cell-to-cell contact and in a
      polarized fashion.
AB  - Measles virus (MV) can infect the central nervous system and, in rare cases,
      causes subacute sclerosing panencephalitis, characterized by a progressive
      degeneration of neurons. The route of MV transmission in neurons was investigated
      in cultured rat hippocampal slices by using MV expressing green fluorescent
      protein. MV infected hippocampal neurons and spread unidirectionally, in a
      retrograde manner, from CA1 to CA3 pyramidal cells and from there to the dentate
      gyrus. Spreading of infection depended on cell-to-cell contact and occurred
      without any detectable release of infectious particles. The role of the viral
      proteins in the retrograde MV transmission was determined by investigating their
      sorting in infected pyramidal cells. MV glycoproteins, the fusion protein (F) and
      hemagglutinin (H), the matrix protein (M), and the phosphoprotein (P), which is
      part of the viral ribonucleoprotein complex, were all sorted to the dendrites.
      While M, P, and H proteins remained more intracellular, the F protein localized
      to prominent, spine-type domains at the surface of infected cells. The detected
      localization of MV proteins suggests that local microfusion events may be
      mediated by the F protein at sites of synaptic contacts and is consistent with a
      mechanism of retrograde transmission of MV infection.

PMID- 11992001
TI  - Pseudotyping Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV): F
      proteins from group II NPVs are functionally analogous to AcMNPV GP64.
AB  - GP64, the major envelope glycoprotein of budded virions of the baculovirus
      Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), is involved in
      viral attachment, mediates membrane fusion during virus entry, and is required
      for efficient virion budding. Thus, GP64 is essential for viral propagation in
      cell culture and in animals. Recent genome sequences from a number of
      baculoviruses show that only a subset of closely related baculoviruses have gp64
      genes, while other baculoviruses have a recently discovered unrelated envelope
      protein named F. F proteins from Lymantria dispar MNPV (LdMNPV) and Spodoptera
      exigua MNPV (SeMNPV) mediate membrane fusion and are therefore thought to serve
      roles similar to that of GP64. To determine whether F proteins are functionally
      analogous to GP64 proteins, we deleted the gp64 gene from an AcMNPV bacmid and
      inserted F protein genes from three different baculoviruses. In addition, we also
      inserted envelope protein genes from vesicular stomatitis virus (VSV) and Thogoto
      virus. Transfection of the gp64-null bacmid DNA into Sf9 cells does not generate
      infectious particles, but this defect was rescued by introducing either the F
      protein gene from LdMNPV or SeMNPV or the G protein gene from VSV. These results
      demonstrate that baculovirus F proteins are functionally analogous to GP64.
      Because baculovirus F proteins appear to be more widespread within the family and
      are much more divergent than GP64 proteins, gp64 may represent the acquisition of
      an envelope protein gene by an ancestral baculovirus. The AcMNPV pseudotyping
      system provides an efficient and powerful method for examining the functions and
      compatibilities of analogous or orthologous viral envelope proteins, and it could
      have important biotechnological applications.

PMID- 11992002
TI  - RelB-p50 NF-kappa B complexes are selectively induced by cytomegalovirus
      immediate-early protein 1: differential regulation of Bcl-x(L) promoter activity
      by NF-kappa B family members.
AB  - The NF-kappa B/Rel family has been implicated in control of transcription of the
      Bcl-x(L) gene, a target which mediates cell survival signals. The cytomegalovirus
      (CMV) immediate-early protein 1 (IE1) was previously shown to induce NF-kappa B
      activity. Here, we report that in both vascular smooth muscle cells (SMCs) and
      NIH 3T3 cells, surprisingly, IE1 failed to induce Bcl-x(L) promoter activity,
      although it induced activity of E8-CAT, a reporter construct driven by two copies
      of the NF-kappa B element upstream of the c-myc promoter (upstream regulatory
      element [URE]). Thus, the subunit nature of the NF-kappa B/Rel factors induced by
      IE1 was examined using immunofluorescence and immunoblotting. IE1 was found to
      selectively induce nuclear RelB and p50 in SMCs and NIH 3T3 cells. An increase in
      RelB protein mediated by IE1 could, in part, be related to an increase in steady
      state relB mRNA levels. Consistent with this subunit identification, IE1 was
      unable to induce E8-CAT activity in relB(-/-) murine embryonic fibroblast cells.
      In cotransfection analysis of SMCs and NIH 3T3 cells, RelB and p50 proteins
      failed to induce Bcl-x(L) promoter activity while inducing E8-CAT. Furthermore,
      the NF-kappa B element of the Bcl-x(L) promoter only weakly bound RelB-p50
      complexes compared to the URE NF-kappa B element. Overall, these findings
      demonstrate in SMCs and NIH 3T3 cells that the CMV IE1 protein selectively
      induces RelB and p50, which fail to activate the Bcl-x(L) promoter, indicating a
      strong specificity of binding and activity for the RelB member of the NF-kappa B
      family. Furthermore, our results implicate RelB in CMV infection of cells such as
      vascular SMCs.

PMID- 11992003
TI  - Human cytomegalovirus US7, US8, US9, and US10 are cytoplasmic glycoproteins, not
      found at cell surfaces, and US9 does not mediate cell-to-cell spread.
AB  - Human cytomegalovirus (HCMV) expresses a large number of membrane proteins with
      unknown functions. One class of these membrane proteins apparently acts to allow
      HCMV to escape detection by the immune system. The best characterized of these
      are the glycoproteins encoded within the US2 to US11 region of the HCMV genome
      that mediate resistance to CD8(+) and CD4(+) T cells. US2, US3, US6, and US11
      block various aspects of the major histocompatibility complex (MHC) class I and
      class II antigen presentation pathways, functioning in cytoplasmic membranes to
      cause retention, degradation, or mislocalization of MHC proteins. Distantly
      homologous genes in this region, US7, US8, US9, and US10, are not well
      characterized. Here, we report expression of the glycoproteins encoded by US7 to
      US10 by using replication-defective adenovirus (Ad) vectors. US7, US9, and US10
      remained sensitive to endoglycosidase H and were exclusively or largely present
      in the endoplasmic reticulum (ER) as determined by confocal microscopy. US8
      reached the Golgi apparatus and trans-Golgi network and was more quickly
      degraded. Previous studies suggested that US9 could localize to cell junctions
      and mediate cell-to-cell spread in ARPE-19 retinal epithelial cells. We found no
      evidence of US9 at cell junctions of HEC-1A epithelial cells. HCMV recombinants
      lacking US9 produced smaller plaques on ARPE-19 cell monolayers but also
      exhibited defects in virus replication compared with wild-type HCMV in these
      cells. Other HCMV recombinants constructed in a similar fashion that were able to
      express US9 also produced small plaques and some of these exhibited defects in
      production of infectious progeny in ARPE-19 cells. Thus, there was no correlation
      between defects in cell-to-cell spread (plaque size) and loss of expression of
      US9, and it is possible that US9(-) mutants produce smaller plaques because they
      produce fewer progeny. Together, our results do not support the hypothesis that
      US9 plays a direct role in HCMV cell-to-cell spread.

PMID- 11992004
TI  - Retrograde transport of transmissible mink encephalopathy within descending motor
      tracts.
AB  - The spread of the abnormal conformation of the prion protein, PrP(Sc), within the
      spinal cord is central to the pathogenesis of transmissible prion diseases, but
      the mechanism of transport has not been determined. For this report, the route of
      transport of the HY strain of transmissible mink encephalopathy (TME), a prion
      disease of mink, in the central nervous system following unilateral inoculation
      into the sciatic nerves of Syrian hamsters was investigated. PrP(Sc) was detected
      at 3 weeks postinfection in the lumbar spinal cord and ascended to the brain at a
      rate of approximately 3.3 mm per day. At 6 weeks postinfection, PrP(Sc) was
      detected in the lateral vestibular nucleus and the interposed nucleus of the
      cerebellum ipsilateral to the site of sciatic nerve inoculation and in the red
      nucleus contralateral to HY TME inoculation. At 9 weeks postinfection, PrP(Sc)
      was detected in the contralateral hind limb motor cortex and reticular thalamic
      nucleus. These patterns of PrP(Sc) brain deposition at various times
      postinfection were consistent with that of HY TME spread from the sciatic nerve
      to the lumbar spinal cord followed by transsynaptic spread and retrograde
      transport to the brain and brain stem along descending spinal tracts (i.e.,
      lateral vestibulospinal, rubrospinal, and corticospinal). The absence of PrP(Sc)
      from the spleen suggested that the lymphoreticular system does not play a role in
      neuroinvasion following sciatic nerve infection. The rapid disease onset
      following sciatic nerve infection demonstrated that HY TME can spread by
      retrograde transport along specific descending motor pathways of the spinal cord
      and, as a result, can initially target brain regions that control vestibular and
      motor functions. The early clinical symptoms of HY TME infection such as head
      tremor and ataxia were consistent with neuronal damage to these brain areas.

PMID- 11992005
TI  - Functional interaction between the pp71 protein of human cytomegalovirus and the
      PML-interacting protein human Daxx.
AB  - The tegument protein pp71 (UL82) of human cytomegalovirus (HCMV) has previously
      been shown to transactivate the major immediate-early enhancer-promoter of HCMV.
      Furthermore, this protein is able to enhance the infectivity of viral DNA and to
      accelerate the infection cycle, suggesting an important regulatory function
      during viral replication. To gain insight into the underlying mechanisms that are
      used by pp71 to exert these pleiotropic effects, we sought for cellular factors
      interacting with pp71 in a yeast two-hybrid screen. Here, we report the isolation
      of the human Daxx (hDaxx) protein as a specific interaction partner of HCMV pp71.
      hDaxx, which was initially described as an adapter protein involved in apoptosis
      regulation, has recently been identified as a nuclear protein that interacts and
      colocalizes with PML in the nuclear domain ND10. In order to assess whether pp71
      can also be detected in ND10 structures, a vector expressing pp71 in fusion with
      the green fluorescent protein was used for transfection of human fibroblasts.
      This revealed a colocalization of pp71 with the ND10 proteins PML and Sp100. In
      addition, cotransfection of a hDaxx expression vector resulted in an enhanced
      recruitment of pp71 to ND10. Targeting of pp71 to nuclear dots could also be
      observed in infected human fibroblasts in the absence of de novo viral protein
      synthesis. Moreover, cotransfection experiments revealed that pp71-mediated
      transactivation of the major immediate-early enhancer-promoter was
      synergistically enhanced in the presence of hDaxx. These results suggest an
      important role of hDaxx for pp71 protein function.

PMID- 11992006
TI  - Evolution of bacteriophage in continuous culture: a model system to test
      antiviral gene therapies for the emergence of phage escape mutants.
AB  - The emergence of viral escape mutants is usually a highly undesirable phenomenon.
      This phenomenon is frequently observed in antiviral drug applications for the
      treatment of viral infections and can undermine long-term therapeutic success.
      Here, we propose a strategy for evaluating a given antiviral approach in terms of
      its potential to provoke the appearance of resistant virus mutants. By use of Q
      beta RNA phage as a model system, the effect of an antiviral gene therapy, i.e.,
      a virus-specific repressor protein expressed by a recombinant Escherichia coli
      host, was studied over the course of more than 100 generations. In 13 experiments
      carried out in parallel, 12 phage populations became resistant and 1 became
      extinct. Sequence analysis revealed that only two distinct phage mutants emerged
      in the 12 surviving phage populations. For both escape mutants, sequence
      variations located in the repressor binding site of the viral genomic RNA, which
      decrease affinity for the repressor protein, conferred resistance to
      translational repression. The results clearly suggest the feasibility of the
      proposed strategy for the evaluation of antiviral approaches in terms of their
      potential to allow resistant mutants to appear. In addition, the strategy proved
      to be a valuable tool for observing virus-specific molecular targets under the
      impact of antiviral drugs.

PMID- 11992007
TI  - Visualization of polydnavirus sequences in a parasitoid wasp chromosome.
AB  - Polydnaviruses, obligatorily associated with endoparasitoid wasps, are unique in
      that their segmented genome is composed of multiple double-stranded DNA circles.
      We present here the first cytological evidence that virus segments are integrated
      in the wasp genome, obtained by using in situ hybridization of virus probes with
      viral sequences in the chromosomes of a wasp from the braconid family of
      hymenopterans.

PMID- 11992008
TI  - Enhanced expression of proinflammatory cytokines in the central nervous system is
      associated with neuroinvasion by simian immunodeficiency virus and the
      development of encephalitis.
AB  - Inflammatory cytokines are believed to play an important role in the pathogenesis
      of human immunodeficiency virus type 1-associated encephalitis. To examine this
      in the simian immunodeficiency virus (SIV)-infected macaque model of neuroAIDS,
      inflammatory cytokine gene expression was evaluated in the brains of macaques
      infected with pathogenic SIV(mac251) by reverse transcriptase PCR. Interleukin-1
      beta was readily detected in the brains of all animals evaluated, regardless of
      infection status or duration of infection. Tumor necrosis factor alpha (TNF
      alpha) and gamma interferon (IFN-gamma) transcripts were undetectable in the
      brains of uninfected control animals but were upregulated at 7 and 14 days
      postinoculation. At the terminal stage of infection, TNF-alpha and IFN-gamma
      transcripts were coexpressed in the brains of four of five animals with SIV
      encephalitis (SIVE). Within an encephalitic brain, TNF-alpha and IFN-gamma
      transcripts were detected in six of seven regions with histologic evidence of
      SIVE, suggesting a direct relationship between neuropathology and altered
      cytokine gene expression. With combined fluorescent in situ hybridization and
      immunofluorescence, TNF-alpha-expressing cells were frequently identified as CD68
      positive macrophages within perivascular lesions. These observations provide
      evidence that cytokines produced by activated inflammatory macrophages are an
      important element in the pathogenesis of SIVE.

PMID- 11992009
TI  - A nucleotide substitution in the tRNA(Lys) primer binding site dramatically
      increases replication of recombinant simian immunodeficiency virus containing a
      human immunodeficiency virus type 1 reverse transcriptase.
AB  - A recombinant simian immunodeficiency virus (SIV) derived from strain 239
      (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency
      virus type 1 (HIV-1) strain HXB2 was severely impaired for replication.
      Detectable p27(Gag) levels were not observed until day 65 and peak p27(Gag)
      levels were not reached until day 75 after transfection of CEMx174 cells with the
      recombinant DNA. Sequences from the latter time point did not contain amino acid
      substitutions in HIV-1 RT; however, a single nucleotide substitution (thymine to
      cytosine) was found at position eight of the SIV primer binding site. We
      engineered an RT/SHIV genome with the thymine-to-cytosine substitution, called
      RT/SHIV/TC, and observed dramatically faster replication kinetics than were
      observed with the parental RT/SHIV from which this variant was derived.
      RT/SHIV/TC provides an improved system for study of the impact of drug resistance
      mutations in HIV-1 RT in a relevant animal model.

PMID- 11992011
TI  - Sequencing of porcine enterovirus groups II and III reveals unique features of
      both virus groups.
AB  - The molecular classification of the porcine enterovirus (PEV) groups II and III
      was investigated. The sequence of the almost complete PEV-8 (group II) genome
      reveals that this virus has unique L and 2A gene regions. A reclassification of
      this group into a new picornavirus genus is suggested. PEV group III viruses are
      typical enteroviruses. They differ from other enteroviruses by a prolonged stem
      loop D of the 5'-cloverleaf structure.

PMID- 11992010
TI  - Bone marrow chimeras reveal non-H-2 hematopoietic control of susceptibility to
      Theiler's virus persistent infection.
AB  - The DA strain of Theiler's murine encephalomyelitis virus persists in the white
      matter of the spinal cords of susceptible mice. Previous results showed that the
      difference in susceptibility to viral persistence between the susceptible SJL/J
      strain and the resistant B10.S strain was due to multiple non-H-2 loci. The
      respective roles of hematopoietic and nonhematopoietic cells in this difference
      have been evaluated with bone marrow chimeras. The results show that non-H-2 loci
      with a major effect on susceptibility are expressed in hematopoietic cells.
      However, the study of the SJL.B10-D10Mit180-D10Mit74 congenic line suggests that
      other loci expressed in nonhematopoietic cells also play a role.

PMID- 11992012
TI  - Mutation spectra of herpes simplex virus type 1 thymidine kinase mutants.
AB  - To examine whether the exonuclease activity intrinsic to the polymerase (Pol) of
      herpes simplex virus type 1 can influence the mutational spectra, we applied the
      denaturing gradient gel electrophoresis (DGGE) system combined with sequencing to
      characterize thymidine kinase mutants isolated from both the wild-type virus and
      a mutant deficient in exonuclease activity, Y7. Wild-type viruses produced
      predominantly frameshift mutations (67%), whereas Y7 replicated a significantly
      lower proportion of frameshifts (21%; P < 0.005). Furthermore, the majority of
      substitutions were transitional changes in both groups, although they distributed
      differently. The implications of these findings are discussed.

PMID- 11992013
TI  - Diarrhea-inducing activity of avian rotavirus NSP4 glycoproteins, which differ
      greatly from mammalian rotavirus NSP4 glycoproteins in deduced amino acid
      sequence in suckling mice.
AB  - Avian rotavirus NSP4 glycoproteins expressed in Escherichia coli acted as
      enterotoxins in suckling mice, as did mammalian rotavirus NSP4 glycoproteins,
      despite great differences in the amino acid sequences. The enterotoxin domain of
      PO-13 NSP4 exists in amino acid residues 109 to 135, a region similar to that
      reported in SA11 NSP4.

PMID- 11992015
TI  - Hippocampal damage and exploratory preferences in rats: memory for objects,
      places, and contexts.
AB  - Rats have a natural tendency to spend more time exploring novel objects than
      familiar objects, and this preference can be used as an index of object
      recognition. Rats also show an exploratory preference for objects in locations
      where they have not previously encountered objects (an index of place memory) and
      for familiar objects in contexts different from those in which the objects were
      originally encountered (an index of context memory). In this experiment, rats
      with cytotoxic lesions of the hippocampal formation were tested on all three
      versions of the novelty-preference paradigm, with a 5-min retention interval
      between the familiarization and test phases. Rats with sham lesions displayed a
      novelty preference on all three trial types, whereas the rats with hippocampal
      lesions displayed a novelty preference on Object trials but did not discriminate
      between the objects on Place trials or Context trials. The findings indicate that
      hippocampal damage impairs memory for contextual or spatial aspects of an
      experience, whereas memory for objects that were part of the same experience are
      left relatively intact.

PMID- 11992014
TI  - Induction of the bovine papillomavirus origin "onion skin"-type DNA replication
      at high E1 protein concentrations in vivo.
AB  - We have studied the replication of plasmids composed of bovine papillomavirus
      type 1 (BPV1) origin of replication and expression cartridges for viral proteins
      E1 and E2 in hamster and mouse cells. We found that the replication mode changed
      dramatically at different expression levels of the E1 protein. At high levels of
      the E1 protein, overreplication of the origin region of the plasmid was observed.
      Analysis of the replication products by one-dimensional and two-dimensional gel
      electrophoresis suggested that initially "onion skin"-type replication
      intermediates were generated, presumably resulting from initiation of the new
      replication forks before the leading fork completed the synthesis of the DNA on
      the episomal plasmid. These replication intermediates served as templates for
      generation of a heterogeneous set of origin region-containing linear fragments by
      displacement synthesis at the partially replicated plasmid. Additionally, the
      linear fragments may have been generated by DNA break-up of the onion skin-type
      intermediates. Analysis of replication products indicated that generated linear
      fragments recombined and formed concatemers or circular molecules, which
      presumably were able to replicate in an E1- and E2-dependent fashion. At moderate
      and low levels of E1, generated by transcription of the E1 open reading frame
      using weaker promoters, DNA replication was initiated at much lower levels, which
      allowed elongation of the replication fork starting from the origin to be more
      balanced and resulted in the generation of full-sized replication products.

PMID- 11992016
TI  - Effects of stress and hippocampal NMDA receptor antagonism on recognition memory
      in rats.
AB  - Exposures to uncontrollable stress have been shown to alter ensuing synaptic
      plasticity in the hippocampus and interfere with hippocampal-dependent spatial
      memory in rats. The present study examined whether stress, which impairs
      hippocampal long-term potentiation (LTP), also affects (nonspatial) hippocampal
      dependent object-recognition memory, as tested on the visual paired comparison
      task (VPC) in rats. After undergoing an inescapable restraint-tailshock stress
      experience, rats exhibited markedly impaired recognition memory at the 3-h (long)
      familiarization-to-test phase delay but not at the 5-min (short) delay. In
      contrast, unstressed control animals showed robust recognition memory (i.e., they
      exhibited reliable preferences for novel over familiar objects) at both short-
      and long-delay periods. The impairing effect of stress on long-delay recognition
      memory was transient because 48 h after undergoing stress experience, animals
      performed normally at the long delay. Similar to stress, microinfusions of DL-2
      amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate receptor
      (NMDAR) antagonist that blocks LTP, into the dorsal hippocampus selectively
      impaired object-recognition memory at the long-delay period. Together, these
      results suggest that stress and intrahippocampal administration of APV affect
      recognition memory by influencing synaptic plasticity in the hippocampus.

PMID- 11992017
TI  - Polysynaptic potentiation at different levels of rat olfactory pathways following
      learning.
AB  - This study was aimed at investigating the consequences of learning on late
      polysynaptic components of evoked field potential signals recorded in parallel at
      different levels of the olfactory pathways. For this, evoked field potentials
      induced by electrical stimulation of the olfactory bulb were recorded
      simultaneously in the anterior piriform cortex, the posterior piriform cortex,
      the lateral entorhinal cortex, and the dentate gyrus. The different parameters of
      late components were measured in each site before and after completion of
      associative learning in anesthetized rats. In the learning task, rats were
      trained to associate electrical stimulation of one olfactory bulb electrode with
      the delivery of sucrose (positive reward) and stimulation of a second olfactory
      bulb electrode with the delivery of quinine (negative reward). In this way,
      stimulation of the same olfactory bulb electrodes used for inducing field
      potentials served as a discriminative cue in the learning paradigm. The data
      confirmed previous observation that learning was associated with a lowering in
      late-component-1 intensity of induction in the posterior piriform cortex. The use
      of simultaneous recording allowed us to further specify the consequences of
      learning on late-component distribution in the studied network. Indeed the data
      showed that whereas before learning, late component 1 was rather uniformly
      distributed among the recorded sites; following learning, its expression was
      facilitated preferentially in the posterior piriform cortex and lateral
      entorhinal cortex. Furthermore, learning was accompanied by the emergence of a
      new late component (late component 2), which occurred simultaneously in the four
      recording sites. The possible involvement of potentiation of polysynaptic
      components in recognition and/or consolidation processes will be discussed.

PMID- 11992019
TI  - Automated assessment of conditioning parameters for context and cued fear in
      mice.
AB  - A behavioral technique often used to evaluate the cognitive performance of rats
      and mice is the fear conditioning paradigm. During conditioned fear experiments,
      freezing responses shown by rodents after exposure to environmental stimuli
      previously paired to an aversive experience provide a behavioral index of the
      animal's associative abilities. The present study examined the ability of a
      computer-controlled automated Freeze Monitor system for recording immobility
      behavior in mice. The sensitivity of the automated procedure to detect group
      differences caused by the application of various training protocols was also
      evaluated. Statistical analyses revealed significant positive correlations
      between immobility scores obtained with the automated apparatus and hand-scored
      data collected by a continuous or a time-sampling method. Behavioral patterns
      recorded by the computerized system were very similar to those obtained by the
      hand-scoring methods adopted. In particular, during context testing, exposure to
      environmental stimuli previously paired with a mild foot shock (unconditioned
      stimulus [US]) evoked increased immobility behavior in mice conditioned with the
      US compared with levels of immobility displayed by mice previously confined to
      the same contextual stimuli without receiving the US. Moreover, although during
      conditioned stimulus (CS) testing, mice previously exposed to the US displayed
      high levels of immobility when confined to environmental cues much different from
      those paired with the US (contextual fear generalization), both hand-scored and
      automated results revealed the effect of CS-US pairing (increased immobility)
      only in mice trained to associate the two stimuli (paired group) but not in mice
      exposed to both CS and US separated by a 40-sec time interval (unpaired group) or
      in mice receiving only the US (US group) during conditioning sessions. Overall,
      the results show associative conditioning measured in an automated apparatus and
      highlight the utility of obtaining both latency as well as beam interruption
      parameters.

PMID- 11992018
TI  - Contact call-driven Zenk protein induction and habituation in telencephalic
      auditory pathways in the Budgerigar (Melopsittacus undulatus): implications for
      understanding vocal learning processes.
AB  - Expression of the immediate early gene protein Zenk (zif 268, egr-1, NGF1A,
      Krox24) was induced in forebrain auditory nuclei in a vocal learning parrot
      species, the budgerigar (Melopsittacus undulatus), when the subjects either
      listened to playbacks of an unfamiliar contact call or to a contact call with
      which they had been familiarized previously. Auditory nuclei included the Field L
      complex (L1, L2a, and L3), the neostriatum intermedium pars ventrolateralis
      (NIVL), the neostriatum adjacent to caudal nucleus basalis (peri-basalis or
      pBas), an area in the frontal lateral neostriatum (NFl), the supracentral nucleus
      of the lateral neostriatum (NLs), and the ventromedial hyperstriatum ventrale
      (HVvm). The latter three nuclei are main sources of auditory input to the vocal
      system. Two patterns of nuclear staining were induced by contact call stimulation
      staining throughout cell nuclei, which was exhibited by at least some neurons in
      all areas examined except L2a and perinucleolar staining, which was the only kind
      of staining exhibited in field L2a. The different patterns of Zenk staining
      indicate that auditory stimulation may regulate the Zenk-dependent transcription
      of different subsets of genes in different auditory nuclei. The numbers of
      neurons expressing Zenk staining increased from seven- to 43-fold over control
      levels when the birds listened to a repeating unfamiliar call. Familiarization of
      the subjects with the call stimulus, through repeated playbacks, greatly reduced
      the induction of Zenk expression to the call when it was presented again after an
      intervening 24-h interval. To determine if neurons exhibiting contact call-driven
      Zenk expression project to the vocal control system, call stimulation was coupled
      with dextran amines pathway tracing. The results indicated that tracer injections
      in the vocal nucleus HVo (oval nucleus of the hyperstriatum ventrale), in fields
      lateral to HVo and in NLs labeled many Zenk-positive neurons in HVvm, NFl, and
      NLs. These results support the idea that, in these neurons, egr-1 couples
      auditory stimulation to the synthesis of proteins involved in either the storing
      of new perceptual engrams for vocal learning or the processing of novel and/or
      meaningful acoustic stimuli related to vocal learning or the context in which it
      occurs.

PMID- 11992020
TI  - Implantable defibrillators for heart failure: a siren's song or a brave new
      world?

PMID- 11992021
TI  - The JT-area indicates dispersion of repolarization in dogs with atrioventricular
      block.
AB  - Heterogeneity in cardiac repolarization (Delta APD) is known to be arrhythmic. In
      the dog model of chronic complete AV-block and acquired long QT syndrome, an
      increase in Delta MAPD (defined as left ventricular monophasic action potential
      duration (MAPD) minus right ventricular MAPD) is often associated with changes in
      T-wave morphology. The purpose of this study was to correlate known changes in
      Delta MAPD with the planimetric total area of the T-wave on the surface ECG
      (integral of J-T, mVx ms). METHODS: The relationship between Delta MAPD and total
      area of the T-wave (i.e., JT-area) was assessed in four different protocols with
      different types of dispersion: (1) class III drugs followed by levcromakalim (n=
      7), (2) LAD coronary artery occlusion and reperfusion (n = 6), (3) dronedarone
      i.v., an amiodarone like agent (n = 5) and (4) steady state pacing at cycle
      lengths of 1000 ms and 500 ms (n = 5). RESULTS: Class III drugs increased Delta
      MAPD (55 +/- 40 ms to 120 +/- 50 ms(#), P<0.05), which was correlated (r = 0.74,
      P < 0.001) with JT-area (50 +/- 40 mV. ms to 95 +/- 35 mV x ms(#)). Ischemia
      increased both Delta MAPD (30 +/- 25 ms to 90 +/- 40 ms(#)) and JT-area (60 +/-
      55 mV x ms to 75 +/- 50 mV x ms(#)). Both levcromakalim and reperfusion reversed
      these conditions. Dronedarone had no effect on Delta MAPD or on JT-area while a
      faster frequency reduced both Delta MAPD and JT-area. CONCLUSION: Changes in
      dispersion of ventricular repolarization are reflected by alterations in JT-area.
      This non-invasive parameter may therefore be used to indicate changes in
      heterogeneity in ventricular repolarization.

PMID- 11992022
TI  - In-vivo electrophysiological study in mice with chronic anterior myocardial
      infarction.
AB  - INTRODUCTION: An increasing number of genetically altered mice with specific
      molecular cardiac defects are being assessed by electrophysiological studies and
      ECG monitoring. This approach should allow for the identification of critical
      genes involved in the arrhythmogenesis in myocardial infarction. Therefore it was
      the aim of this study to establish a standard for the in-vivo
      electrophysiological characteristics in the mouse model of chronic anterior
      myocardial infarction. METHODS AND RESULTS: Using a minimized, invasive, in-vivo
      electrophysiological study, surface ECG parameters, sinus node function, atrial,
      atrio-ventricular and ventricular conduction and ventricular repolarization, and
      enhanced vulnerability to atrial and ventricular arrhythmia were studied in 20
      wild-type C57BL/6 mice either under control or 11 weeks after large anterior
      myocardial infarction induced by ligation of the left anterior descending
      coronary artery. Telemetric ECG recording was performed in the same animals at
      baseline unrestrained, conscious condition to study surface ECG parameters, heart
      rate variability and the prevalence of supraventricular and ventricular
      arrhythmia. During electrophysiological study, infarcted mice showed an 81%
      increase of the angle of the QRS axis (p < 0.001) and a prolongation of the P
      wave by 23% (p = 0.01), the QRS complex by 39% (p = 0.001), the QT interval by
      23% (p<0.05), the QT(c) interval by 30% (p < 0.005) and the JT(c) interval by 31%
      (p < 0.05) in comparison to control animals. Furthermore, there was a
      prolongation of the atrio-ventricular interval by 28% (p < 0.0005) and the atrio
      ventricular functional refractory period by 26% in infarcted animals (p < 0.05),
      and inducibility of ventricular tachycardia in 4 of 6 infarcted versus in none of
      control animals (0 < 0.01). During telemetric ECG recording, there was a marked
      increase in ventricular ectopic activity in infarcted mice in comparison to
      controls (p < 0.05). Heart rate and time- and frequency-domain of heart rate
      variability were not significantly different in both groups (p > 0.05,
      respectively). CONCLUSIONS: The mouse model of chronic anterior myocardial
      infarction is associated with significant atrial and ventricular conduction
      disturbances and vulnerability to ventricular arrhythmia and thus may provide a
      highly valuable tool to study molecular determinants of arrhythmogenesis in
      myocardial infarction.

PMID- 11992023
TI  - Difference in mechanical atrioventricular delay between atrial sensing and atrial
      pacing modes in patients with hypertrophic and dilated cardiomyopathy: an
      electrical hemodynamic catheterization study.
AB  - For optimal pacemaker programming in patients with cardiomyopathy, it is
      important to understand the relationship between the programmed right atrial and
      ventricular delay and the mechanical contraction delay of the left atrium and
      left ventricle. METHODS: We analyzed data from 34 patients with dilated
      cardiomyopathy (14) or hypertrophic obstructive cardiomyopathy (20) who had dual
      chamber P-synchronous pacing (VDD) and atrioventricular sequential pacing (DVI)
      during hemodynamic catheterization. Using multiple atrioventricular intervals
      during VDD and DVI pacing, the relationship of the programmed right atrial-right
      ventricular interval to the mechanical left atrial-left ventricular delay
      (assessed by high-fidelity pressures) was determined. RESULTS: We found that the
      optimal mechanical left atrial-left ventricular delay was 120 ms, which required
      a programmed right atrial-right ventricular interval of 160 ms during DVI pacing.
      Also, the mean difference in right atrial-right ventricular pacing interval
      between VDD and DVI modes was 54 +/- 28 ms (range, 10-120 ms) in the hypertrophic
      obstructive cardiomyopathy group and 64 +/- 38 ms (range, 20-150 ms) in the
      dilated cardiomyopathy group. CONCLUSIONS: We concluded that the optimal right
      atrial-right ventricular interval during DVI pacing was 160 ms and that, to
      achieve the same mechanical left atrial-left ventricular delay, the programmed
      right atrial-right ventricular interval during VDD pacing was approximately 50 ms
      to 60 ms shorter than during DVI pacing. However, the difference of electrical
      atrioventricular pacing interval in VDD and DVI may vary widely from patient to
      patient.

PMID- 11992024
TI  - Dual site right atrial pacing in the prevention of symptomatic atrial
      fibrillation refractory to drug therapy and unrelated to sinus bradycardia.
AB  - Dual-site right atrial pacing has been shown recently to prevent atrial
      fibrillation relapses in patients affected by drug-refractory, highly-recurring
      tachyarrhythmia, associated to sinus bradycardia. The aim of our study was to
      verify whether this stimulation modality could be useful in patients affected by
      refractory atrial fibrillation unassociated to sinus bradycardia. METHODS AND
      RESULTS: Fifteen patients (6 males) affected by refractory, symptomatic atrial
      fibrillation, and potential candidates to AV node ablation, were prospectively
      enrolled. Mean age was 65 +/- 5 years (range 62-78). Associated pathology was
      arterial hypertension in 12, and dilated cardiomyopathy in 3. Eight patients were
      affected by persistent atrial fibrillation, and seven by paroxysmal atrial
      fibrillation. The duration of the arrhythmia was 61 +/- 63 months (range 3-216).
      Left atrial diameter was 39.4 +/- 4.2 mm (range 33-46), left ventricular end
      diastolic diameter was 52.4 +/- 12.2 mm (range 41-90), and left ventricular
      ejection fraction was 55 +/- 16 (range 18-81). Single chamber atrial pacing was
      used in 10 patients, dual chamber in 5 patients. The mean duration of follow up
      was 24 +/- 12 months (range 3-41). During this period the number of episodes of
      atrial fibrillation decreased from a mean of 13 +/- 38 (range 1-150) to 0.4 +/-
      0.7 (range 0-2.3) per month (p < 0.001). In the subgroup of patients with
      persistent atrial fibrillation the number of episodes decreased from a mean of
      20.4 +/- 52.4 (range 1-150) to 0.6 +/- 0.9 (range 0-2.3) (p < 0.001). In patients
      with paroxysmal atrial fibrillation the number of episodes decreased from 4.6 +/-
      3.5 (range 2-12) to 0.2 +/- 0.5 (range 0-1.4) (p < 0.001). One patient (6.7%)
      developed chronic atrial fibrillation 16 months after the implant, 2 remaining
      patients (13%) had their arrhythmia unaltered. After the implant the number of
      Class 1 antiarrhythmic drugs fell from 18 to 6 (p < 0.001) and that of Class 2
      changed from 0 to 7 p < 0.001). The use of Class 3 and 4 did not change
      significantly. No complications related to implant were observed. CONCLUSIONS:
      Permanent dual-site right atrial pacing can prevent atrial fibrillation
      recurrences in patients affected by highly symptomatic episodes unassociated to
      sinus bradycardia.

PMID- 11992025
TI  - Transseptal activation during left atrial pacing in humans: electroanatomic
      mapping using a noncontact catheter and the intracardiac echocardiography.
AB  - BACKGROUND: A better understanding of transseptal activation may be important for
      the treatment of atrial fibrillation, but little is known about preferential
      routes of conduction from the left atrium (LA) to the right atrium (RA) in
      humans. METHODS AND RESULTS: Twelve patients were studied. A noncontact mapping
      system was used to map the RA during pacing from several sites of LA at different
      cycle lengths. The location of the Bachmann's bundle (BB), the fossa ovalis (FO)
      and the coronary sinus (CS) ostium were determined using intracardiac
      echocardiography. The BB was the earliest area of right atrial activation during
      pacing from the atrial appendage, roof and postero-superior wall in 94% of cases.
      The FO was the area of earliest activation during pacing from the septum and the
      right superior pulmonary veins (PV) in 95% of cases. The CS ostium (alone or
      associated with the FO) was the region of transseptal breakthrough in all
      patients during pacing from the right inferior PV, postero-inferior wall and
      distal CS. Various patterns of activation with 2 or 3 distinct areas of
      transseptal breakthrough were observed during pacing from the lateral wall and
      the left superior PV. The pacing cycle length did not influence the modality of
      transseptal activation. CONCLUSIONS: Different patterns of transseptal activation
      were found during pacing from LA. The preferential routes of conduction from the
      LA to the RA were related to the sites of stimulation and were not influenced by
      the pacing cycle length.

PMID- 11992026
TI  - Clinical AV nodal reentrant tachycardia in a patient with left sided accessory
      pathway and immediate occurrence of antidromic AV reentrant tachycardia after
      slow pathway ablation.
AB  - The only inducible arrhythmia in a patient with exclusive antegrade conducting
      left anterolateral accessory pathway, consists of slow/fast atrioventricular
      nodal reentrant tachycardia. After radiofrequency catheter ablation of the slow
      pathway, true antidromic AV reentrant tachycardia was easily induced by atrial
      pacing. Following ablation of the accessory pathway no arrhythmia could be
      induced.

PMID- 11992027
TI  - Catheter ablation of inducible atrial flutter, in combination with atrial pacing
      and antiarrhythmic drugs ("hybrid therapy") improves rhythm control in patients
      with refractory atrial fibrillation.
AB  - Atrial flutter or tachycardia may coexist with atrial fibrillation [AF] and can
      be treated with ablation techniques in attempt to reduce the total AF burden. The
      role of ablation of latent atrial tachyarrhythmias elicited at electrophysiologic
      study in conjunction with atrial pacing and antiarrhythmic drugs in patients with
      refractory AF has not been evaluated. We evaluated the efficacy of catheter
      ablation of electrically induced atrial flutter or atrial tachycardia in
      improving rhythm control in patients with refractory AF. METHODS: Consecutive
      patients with refractory AF, and spontaneous atrial flutter (Group 1) or without
      spontaneous atrial flutter (Group 2) underwent programmed stimulation in a
      baseline drug-free state. All patients had electrically induced atrial flutter or
      tachycardia. Radiofrequency ablation of the arrhythmia substrate was performed in
      all patients. Primary endpoints evaluated for patient outcome in both groups
      included maintenance of rhythm control and freedom from recurrent atrial
      tachyarrhythmias. RESULTS: Forty-three patients, with a mean age of 66 +/- 13
      years were studied. Group 1 consisted of 22 patients while Group 2 had 21
      patients. Ablation of the tricuspid valve-inferior venacaval isthmus was
      performed in 41 patients who had common atrial flutter induced at
      electrophysiologic study. Ablation of other atrial sites was performed in 8
      patients with induced atypical flutter and 4 patients with induced atrial
      tachycardia. Ten of these patients had ablation of more than one arrhythmia. 17
      patients (40%) had atrial pacing instituted and 28 patients remained on a class
      1/3 antiarrhythmic drug. During a mean follow-up of 26 +/- 14 months, 33 patients
      (82.5%) remained in rhythm control. Actuarial analysis showed 96% of patients in
      rhythm control at 6 months, 94% at 12 months, and 90% at 24 months. Freedom from
      symptomatic AF recurrence was 64% at 6 months, 58% at 12 months, and 42% at 24
      months. The outcome for both of these endpoints was similar for Group 1 and Group
      2 (p = NS). The AF free interval increased significantly from 7+/- 9 days to 172
      +/- 121 days (p < 0.01) after ablation. This increase was again similar in both
      the groups. In the 14 patients were who did not receive atrial pacing and who
      remained on the same class 1/3 antiarrhythmic drug, the AF free interval
      increased from 18 +/- 17 days to 212+/- 102 days (p < 0.01). CONCLUSIONS: We
      conclude that electrophysiologic studies can elicit latent atrial flutter or
      tachycardia in patients with refractory AF without spontaneous monomorphic atrial
      tachyarrhythmias. Catheter ablation of electrically induced atrial flutter or
      tachycardia either alone, or with atrial pacing and with antiarrhythmic drug may
      improve rhythm control and reduce AF recurrences. This is similar in patients
      with and without spontaneous atrial flutter and refractory AF.

PMID- 11992028
TI  - Early versus late atrial fibrillation after atrial flutter ablation.
AB  - INTRODUCTION: Radiofrequency catheter ablation of atrial flutter (AFl) has high
      initial success with a 10-15% recurrence. Atrial fibrillation (AFib) after
      radiofrequency catheter ablation of AFl can occur but may be transient (lasting
      no more than four weeks). METHODS: Of one hundred seventeen consecutive patients
      studied, one hundred and four consecutive patients with sustained, symptomatic
      AFl, as the predominant rhythm disturbance (some of whom had transient pre
      ablation AFib), referred for radiofrequency catheter ablation, had clinical
      follow-up. All had evidence for successful AFl ablation. Patients were followed
      prospectively. RESULTS: Over a mean follow-up of 28 months, 28 patients developed
      AFib after ablation of AFl [12 early AFib (<2 months) and 16 late AFib (>2
      months)]. Seven of 12 (58%) patients in the early onset group reverted to normal
      sinus rhythm; none required long-term antiarrhythmic therapy. Only one (8%)
      developed permanent AFib. No patient in the late onset group remained in sinus
      rhythm without an antiarrhythmic drug. Three (19%) developed permanent AFib
      despite therapy among those with late onset AFib. Two (17%) patients with early
      onset AFib reverted to normal sinus rhythm with treatment versus 5 (31%) in the
      late onset group. Finally, only 2 patients (17%) with paroxysmal/persistent
      episodes of Afib from the early onset group stayed in normal sinus rhythm despite
      therapy, while 8 patients (50%) with paroxysmal/persistent AFib episodes from the
      late onset group required therapy to maintain normal sinus rhythm. CONCLUSION:
      Early onset AFib after ablation of AFl is likely to be transient and self
      limited. Late onset AFib after ablation of AFl can persist and require chronic
      therapy.

PMID- 11992029
TI  - Atrial fibrillation after atrial flutter ablation.

PMID- 11992030
TI  - Successful ablation of Hisian ectopy identified by a reversed His bundle
      activation sequence.
AB  - Junctional ectopy or tachycardia have been mapped and ablated in the
      atrioventricular node or its posterior extensions. There is no report of Hisian
      ectopy convincingly demonstrated and then successfully treated by ablation. A 39
      year-old man presented with a 9-year history of recurrent supraventricular ectopy
      refractory to medical treatment. Intracardiac mapping revealed that the ectopy
      originated from the His bundle, which was indicated by a reversed His bundle
      activation sequence during ectopy compared to that during sinus rhythm, while the
      right bundle branch potential was anterogradely activated. Low power RF energy
      delivered to the site of earliest activation completely abolished the ectopic
      activity without modification of Hisian or atrioventricular conduction. After a
      12-month followup, the patient remains free of recurrence.

PMID- 11992031
TI  - The use of radiofrequency catheter ablation to extract a chronic permanent
      pacemaker lead after failed laser extraction.
AB  - Even with the latest advances in pacemaker lead extraction techniques, successful
      lead extraction via percutaneous techniques still cannot be achieved in up to 2%
      of procedures at qualified centers reiterating the need for further development
      in this area. We present an example of a novel technique using radiofrequency
      (RF) energy delivered with a steerable ablation catheter to facilitate lead
      removal using an 8-french guiding sheath (SRO, Daig corporation) and a
      bidirectional steerable 4 mm tip ablation catheter (EPT). With a short series of
      RF ablations, the pacemaker lead tip was successfully freed without
      complications.

PMID- 11992032
TI  - Late recovery of surgically-induced atrioventricular block in patients with
      congenital heart disease.
AB  - OBJECTIVES: To assess the incidence and establish possible predictors of late
      recovery of post-surgical heart block, treated with pacemaker implantation, in
      patients with congenital heart defects. BACKGROUND: The American College of
      Cardiology/American Heart Association Task Force has recommended pacemaker
      implantation for advanced second or third degree atrioventricular block which
      persists for 7 to 14 days after surgery. The incidence of late recovery of post
      surgical heart block following pacemaker implantation has not been reported.
      METHODS: Records of 44 patients with post-surgical heart block who underwent
      pacemaker implantation at our institutions since 1976 were reviewed for
      demographic, anatomic, surgical and surface electrocardiographic data to assess
      the incidence of, and factors associated with, recovery of atrioventricular
      conduction on long-term follow-up. RESULTS: 32% (14) of patients recovered
      atrioventricular conduction at a median follow-up of 5.5 years while 68% (30)
      remained pacemaker dependent. The groups were similar in age and weight at
      surgery and period of follow-up p = 0.5). Types of defect and surgical repair
      were not significantly different (p > 0.1). There was a similar number of
      patients with second degree-type II block in both groups (p = 0.15). The groups
      did not differ in timing of pacemaker implantation (<10 days p = 0.14, >14 days p
      = 0.18). CONCLUSIONS: Late recovery of atrioventricular conduction following
      pacemaker implantation for postsurgical heart block is common. However, clinical
      predictors, with reference to current recommendations, could not be identified.
      Prospective electrophysiologic evaluations may be warranted to establish
      guidelines for long term pacemaker dependency and criteria for pacing.

PMID- 11992035
TI  - Normal and abnormal development of the kidney: a clinician's interpretation of
      current knowledge.
AB  - PURPOSE: The recent basic science literature is replete with new discoveries in
      the molecular genetics of renal development. However, little of this information
      has filtered into urological textbooks and journals. An effort is made herein to
      integrate these new findings and propose a more sophisticated blueprint of renal
      development than the one traditionally taught in medical school and residency. To
      accomplish this goal the author offers simple definitions and interpretations of
      complicated terms and events, and points out how maldevelopment results when
      mutations take place. MATERIALS AND METHODS: A review of recent advances in the
      molecular genetics of renal development and maldevelopment was done. RESULTS:
      Renal metanephric development results from the expression of many genes in the
      ureteral bud and metanephric blastema with each sending messages to the other to
      induce organogenesis. CONCLUSIONS: Currently an understanding of normal renal
      organogenesis stems from a study of disease states resulting from perturbations
      in molecular genetics. In turn, a better understanding of normal renal
      organogenesis facilitates an understanding of how dysplasia, hypoplasia, cystic
      disease and tumors develop when molecular genetics go awry. For each form of
      renal dysgenesis and for most renal tumors 1 or more gene defects are eventually
      identified. The young urologist based in these new discoveries would be better
      prepared to make the breakthroughs in the future that are necessary for advancing
      the prevention and management of these conditions.

PMID- 11992036
TI  - Mechanical and antibiotic bowel preparation for urinary diversion surgery.
AB  - PURPOSE: We reviewed the existing scientific literature regarding the efficacy of
      preoperative mechanical and antibiotic bowel preparation for urinary diversion
      surgery. MATERIALS AND METHODS: We performed MEDLINE searches of the literature
      from 1966 through 2000 and obtained additional references through a review of the
      bibliographies of select articles. RESULTS: For urinary diversion surgery
      information regarding appropriate mechanical and antibiotic bowel preparation is
      scant. The colorectal surgery literature indicates that oral sodium phosphate
      appears to be better tolerated than polyethylene glycol and is as effective,
      although the latter is preferred in patients with compromised renal, cardiac or
      liver function. A combination of oral and parenteral antibiotics should be used
      for all urinary reconstructive surgeries involving gastrointestinal tract
      segments. A parenteral second generation cephalosporin antibiotic should be given
      within 1 hour of skin incision and repeated at an interval of twice the
      antibiotic serum half-life or when blood loss exceeds 1 l. CONCLUSIONS: For
      urinary diversion surgery contemporary methods of mechanical and antibiotic bowel
      preparation appear to be safe, effective and better tolerated than traditional
      bowel preparation methods.

PMID- 11992037
TI  - Small-Carrion penile prosthesis: a report on 160 cases and review of the
      literature. 1978.

PMID- 11992038
TI  - Changes in bone mineral density, lean body mass and fat content as measured by
      dual energy x-ray absorptiometry in patients with prostate cancer without
      apparent bone metastases given androgen deprivation therapy.
AB  - PURPOSE: We characterize the consequences of androgen deprivation therapy on body
      composition in elderly men. MATERIALS AND METHODS: Using a dual energy x-ray
      absorptiometry instrument, we determined the changes in bone mineral density,
      bone mineral content, fat body mass and lean body mass in 35 patients with
      prostate cancer without bone metastases who received luteinizing hormone
      releasing hormone analogue for 12 months. RESULTS: At baseline conditions 46% of
      cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine
      and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation
      significantly decreased bone mineral density either at the lumbar spine (mean
      gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6
      and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144]
      and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was
      found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone
      mineral content paralleled the bone mineral density pattern. Lean body mass
      decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p
      <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724
      [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS: Serial bone densitometry
      evaluation during androgen deprivation therapy may allow the detection of
      patients with prostate cancer at risk for osteoporotic fractures, that is those
      with osteopenia or osteoporosis at baseline and fast bone loss. The change in
      body composition may predispose patients to accidental falls, thus increasing the
      risk of bone fracture.

PMID- 11992039
TI  - Subjective and objective comparison of critical care pathways for open donor
      nephrectomy.
AB  - PURPOSE: In the era of minimally invasive techniques and cost containment, care
      pathways after donor nephrectomy are important. While open donor nephrectomy
      remains the established procedure, questions regarding the surgical approach,
      postoperative care and patient morbidity/dissatisfaction have surfaced. We
      compared results of standard and fast-track care pathways after donor
      nephrectomy. MATERIALS AND METHODS: Between January 1998 and August 1999, 60
      patients underwent open donor nephrectomy. By surgeon preference, patients
      received either ketorolac only (31), ketorolac plus morphine spinal (17) or
      patient controlled anesthesia (12). Data related to surgery, hospital course and
      cost were reviewed. Patients were surveyed regarding return to daily activities
      and groups were statistically analyzed. RESULTS: The mean dose per patient was
      183 (ketorolac only), 180 (ketorolac plus morphine spinal) and 69 (patient
      controlled analgesia) mg. Median hospital stay was 2 days for the fast-track
      pathways (ketorolac only, ketorolac plus morphine spinal) compared to 3 days for
      the patient controlled analgesia group (p <0.001). Delayed oral intake was seen
      in 6% of patients on ketorolac only and 3% for those on ketorolac plus morphine
      spinal compared to 83% of the patient controlled analgesia group (p <0.001).
      Return to exercise (median weeks, p <0.79) was 2 for the ketorolac only group,
      3.5 for ketorolac plus morphine spinal and 3.5 for patient controlled analgesia.
      Mean global cost was $9,394 for the ketorolac only group, $9,238 for ketorolac
      plus morphine spinal and $11,601 for patient controlled analgesia (p <0.02).
      CONCLUSIONS: Fast-track pathways significantly shortened hospital stay and
      quickened oral intake. Cost was significantly contained using new pathways.
      Resumption of daily activities was comparable among the groups. Comparisons of
      critical care pathways are required to optimize patient care after kidney
      donation. Prospective trials are needed to verify our results.

PMID- 11992040
TI  - Influence of gender and age on calcium oxalate crystal growth inhibition by urine
      from relatives of stone forming patients.
AB  - PURPOSE: We define the relationships between urine inhibition of calcium oxalate
      crystal growth and age, gender, urine chemistries and stone formation among
      relatives of calcium stone forming patients. MATERIALS AND METHODS: We collected
      24-hour urine samples from 366 first degree relatives of calcium stone formers.
      Calcium oxalate crystal growth inhibition was studied using a constant amount of
      dialyzed urine protein in a seeded crystallization system. Standard stone risk
      measurements were also performed on the urine, including supersaturation for
      calcium oxalate, calcium phosphate and uric acid. RESULTS: By multivariate
      analysis crystal growth inhibition is strongly inversely related to the amount of
      protein excreted per day, and the age of the subject. When corrected for protein
      excretion and age, urine proteins from nonstone forming male subjects inhibited
      crystal growth more strongly than those from corresponding female subjects. Among
      stone formers the sex difference was not present. CONCLUSIONS: Inhibition of
      calcium oxalate crystal growth is influenced by a complex combination of gender,
      age, stone formation and assay conditions. The effect of daily protein excretion
      is most likely a consequence of using a fixed amount of urine protein per assay.
      The influence of age is significant and unexplained, with the urine of young
      people (less than 20 years) demonstrating a vigorous ability to inhibit
      crystallization. In addition, the urine of nonstone forming male relatives
      appears to have a greater ability to inhibit crystallization than that of
      nonstone forming female relatives. Further use of this assay in clinical
      investigations must take age and gender into proper account.

PMID- 11992041
TI  - Bare naked baskets: ureteroscope deflection and flow characteristics with intact
      and disassembled ureteroscopic nitinol stone baskets.
AB  - PURPOSE: Lower pole renal access during flexible ureterorenoscopy is often
      limited by the active deflection capabilities of the ureteroscope. Deterioration
      in the deflection and flow capabilities of ureteroscopes occurs with the passage
      of instrumentation through the working channel. We performed in vitro evaluation
      of a novel technique using unsheathed nitinol baskets to minimize the
      deterioration in deflection and maximize the irrigant flow associated with
      instrument passage through the working channel during flexible ureterorenoscopy.
      MATERIALS AND METHODS: Alterations in the irrigant flow and active deflection of
      4 ureteroscopes from different manufacturers were evaluated. Each ureteroscope
      was evaluated with an empty working channel, and then with sheathed and
      unsheathed 2.2, 3 and 3.2Fr (Cook Urological, Inc., Indianapolis, Indiana), 2.4
      and 3Fr (Microvasive Urology, Natick, Massachusetts) nitinol baskets in the
      working channel. RESULTS: With all baskets tested and in all ureteroscopes the
      deterioration in active deflection and irrigant flow was improved with the
      unsheathed baskets. The disassembled basket within the working channel allowed an
      additional 15 to 20 degrees of active deflection. In addition, the disassembled
      basket allowed for a 2 to 30-fold increase in irrigant flow compared with an
      intact basket. CONCLUSIONS: The combination of improved deflection and irrigant
      flow with this technique may improve ureteroscopic access to lower pole renal
      calculi.

PMID- 11992042
TI  - Survey of urological laparoscopic practices in the state of California.
AB  - PURPOSE: In the interest of maintaining our surgical domain we performed a survey
      aimed at establishing laparoscopic practice patterns as they pertain to
      urological disease. MATERIALS AND METHODS: Surveys were mailed to 2,902 surgeons
      in California who were listed with the American College of Surgeons, including
      2,175 general surgeons, 510 urologists and 217 obstetricians-gynecologists.
      RESULTS: A total of 442 complete responses (15.2%) were tallied. Of urologists
      and of nonurologists 54% and 11% performed no laparoscopy, while 12% and 80%,
      respectively, devoted at least 5% of their time to laparoscopic surgery.
      Urologists and nonurologists performing no laparoscopy were older than those
      performing a significant volume (p < 0.05). Of urologists 16% thought that they
      were trained adequately during residency to perform laparoscopic surgery compared
      with 30% of nonurologists. Of the urologists who performed hand assisted
      laparoscopy, 50% tended to use it as a means of gaining familiarity with these
      techniques. These urologists performed more laparoscopic surgery than other
      urologists. While 80% of laparoscopy cases were community based, academic
      urologists are actively interested in laparoscopic surgery. The 2 most important
      reasons cited for performing laparoscopy were more rapid recovery and decreased
      morbidity. The leading laparoscopic procedures according to incidence for
      urologists performing laparoscopic surgery were diagnostic procedures (12.9%),
      varicocelectomy (12.1%), adrenalectomy (9.7%), pelvic lymphadenectomy (8.9%), and
      simple nephrectomy and renal cyst decortication (8.1% each). The leading
      laparoscopic cases according to the number of available cases per urologist were
      colposuspension-bladder neck suspension (1.06), donor nephrectomy (0.77), pelvic
      lymphadenectomy (0.52), varicocelectomy (0.48) and orchiopexy (0.45). Urologists
      performed more urological laparoscopy cases than nonurologists. CONCLUSIONS:
      Urological laparoscopic practice in California remains in its infancy. It is
      imperative that exposure should be increased in residency training programs.

PMID- 11992043
TI  - Comparison of hand assisted and standard laparoscopic radical nephroureterectomy
      for the management of localized transitional cell carcinoma.
AB  - PURPOSE: Hand assisted laparoscopy affords the surgeon tactile sensation and
      blunt dissection, which are currently limited using the standard laparoscopic
      technique. Therefore, we compared standard and hand assisted laparoscopic radical
      nephroureterectomy for localized upper tract transitional cell carcinoma.
      MATERIALS AND METHODS: The medical records of 27 patients who underwent standard
      (11) or hand assisted (16) laparoscopic radical nephroureterectomy between April
      1998 and January 2001 were retrospectively reviewed. The parameters of efficacy,
      efficiency, safety and convalescence were compared. RESULTS: Mean patient age was
      64 and 66 years (p = 0.72) in the standard and hand assisted groups, and the mean
      American Society of Anesthesiologists score was 2.5 and 2.7 (p = 0.64),
      respectively. All standard and 15 of the 16 hand assisted (94%) procedures were
      successfully completed via laparoscopy. Total operative time was more than 1 hour
      shorter for hand assisted than for laparoscopic radical nephroureterectomy (4.9
      versus 6.1 hours, p = 0.055). Mean estimated blood loss was similar in the
      standard and hand assisted groups (190 and 201 ml., p = 0.78). In each group 1
      patient required blood transfusion. Mean specimen weight was significantly higher
      in hand assisted cases (576 versus 335 gm., p = 0.036). Mean time to oral intake
      was similar in patients who underwent standard and hand assisted laparoscopic
      radical nephroureterectomy (13 and 20 hours, respectively, p = 0.45). The mean
      analgesic requirement was also similar (29 and 33 mg. morphine sulfate,
      respectively, p = 0.83). Mean hospital stay in uncomplicated cases was similar
      for standard and hand assisted surgery (2.9 and 2.5 days, respectively). Overall
      hospital stay in the 2 cohorts was also similar (3.3 and 4.5 days, respectively,
      p = 0.59). Four patients per group experienced postoperative complications. There
      were no deaths in the standard group but 1 patient (6%) in the hand assisted
      group died postoperatively. Mean time to partial and complete convalescence in
      the standard and hand assisted groups was 2.4 and 5.2, and 3.5 and 8.0 weeks,
      while mean followup was 27.4 and 9.6 months, respectively. CONCLUSIONS: Compared
      with standard laparoscopy hand assisted laparoscopy decreases operative time
      without significantly altering short-term parameters of convalescence. However,
      long-term convalescence after hand assisted laparoscopic radical
      nephroureterectomy is 1 to 3 weeks longer (p = 0.27). Longer followup in the hand
      assisted cohort is necessary to determine whether there are any differences in
      the 2 methods in regard to cancer control.

PMID- 11992044
TI  - Renal cell carcinoma invading the urinary collecting system: implications for
      staging.
AB  - PURPOSE: Current TNM staging of renal cell carcinoma is based on the tumor
      propensity for local extension (T), nodal involvement (N) and metastatic spread
      (M). Locally advanced renal cell carcinoma may involve the perirenal fat, adrenal
      glands, renal vein, vena cava and/or urinary collecting system. The existing TNM
      classification does not reflect the ability of renal cell carcinoma to invade the
      urothelium. We evaluated the incidence and characteristics as well as overall and
      cancer specific survival of renal cell carcinoma invading the urinary collecting
      system. METHODS AND MATERIALS: We reviewed pathological findings in 504 kidneys
      from 475 patients with renal cell carcinoma who presented to our institution in a
      3-year period. Urothelial involvement required evidence of gross or histological
      invasion of the renal calices, infundibulum, pelvis or ureter. Demographic and
      survival data were obtained from medical records and an institutional cancer
      registry for tumors invading the urothelium. Stage specific survival data were
      then compared with tumors not involving the urinary collecting system. RESULTS:
      Definitive urothelial involvement by the primary tumor was interpretable in 426
      of 504 kidneys. Invasion of the collecting system was identified in 61 of 426
      cases (14%). Mean diameter of the invading lesions was 10.2 cm. (range 3 to 26).
      The majority of cases showed clear cell and sarcomatoid histology. Invasion by a
      papillary lesion was rare. Involvement of the collecting system was most common
      at the renal poles. Of 61 lesions invading the collecting system 48 (79%) were
      stage pT3 or greater, while only 13 (21%) were pathologically localized stage pT2
      or less. Vascular invasion was identified in 38 renal cell carcinoma cases (62%)
      with urothelial involvement. A total of 16 cases (26%) were associated with vena
      caval thrombus. Invading tumors were high Fuhrman grade III or IV in 43 cases
      (70%). Overall disease specific survival was poor with a median of 19 months. In
      patients with localized stage pT1 or pT2N0M0 disease and urothelial invasion
      median disease specific survival was 46 months. CONCLUSIONS: Renal cell carcinoma
      lesions involving the renal collecting system are characteristically large, high
      grade and high stage. Clear cell carcinoma most commonly invades, while invasion
      by papillary tumors is rare. Overall the prognosis for high stage lesions with
      urothelial involvement is poor and does not appear significantly different from
      the reported disease specific survival of patients with high stage lesions
      without urothelial invasion. Localized tumors 4 cm. or less, which are amenable
      to elective nephron sparing surgery, rarely invade the urothelium. However, when
      a low stage pT2 or less renal lesion involves the urinary space, survival appears
      worse than equivalently staged renal cell carcinoma without invasion. Including
      urothelial invasion into current TNM staging systems for renal cell carcinoma is
      unlikely to provide significant additional prognostic or therapeutic information.

PMID- 11992045
TI  - High intensity focused ultrasound as noninvasive therapy for multilocal renal
      cell carcinoma: case study and review of the literature.
AB  - PURPOSE: Noninvasive tumor ablation can be achieved by extracorporeally induced
      high intensity focused ultrasound. Clinical high intensity focused ultrasound
      performed to date for renal tumors have only been experimental in nature. We
      present specific details on a patient with renal cell carcinoma who underwent
      high intensity focused ultrasound with curative intent and long-term followup
      examinations. MATERIALS AND METHODS: Ultrasound waves were generated by a
      cylindrical piezoelectric element focused by a paraboloid reflector. High
      intensity focused ultrasound was applied to 3 tumors in 3 sessions with the
      patient under general anesthesia or sedation analgesia, followed by magnetic
      resonance imaging for 6 months. RESULTS: After treatment magnetic resonance
      imaging showed necrosis in the 2 tumors in the lower kidney pole within 17 and 48
      days, respectively. The necrotic tumor area shrank thereafter within 6 months.
      The tumor in the upper pole was not affected by treatment due to absorption of
      the ultrasound energy by the interposed ribs. General anesthesia was required to
      apply high energy levels of focused ultrasound. Absorption of high intensity
      focused ultrasound in the tissue induced sharply demarcated thermonecrosis. For
      50 years patients have been treated with high intensity focused ultrasound for
      different indications, focusing on the brain, eyes, prostate, liver and bladder.
      For the kidney experimental but only few clinical studies indicate sufficient
      tissue ablation. CONCLUSIONS: In our case contactless noninvasive application of
      high intensity focused ultrasound to 2 renal carcinomas achieved thermal
      ablation. When high intensity focused ultrasound energy was coupled correctly, no
      lesions occurred outside of the target area. Successful high intensity focused
      ultrasound application depended on optimum energy coupling, a sufficiently high
      ultrasound energy level and general anesthesia.

PMID- 11992046
TI  - Accurate pathological staging of urothelial neoplasms requires better cystoscopic
      sampling.
AB  - PURPOSE: The frequency with which muscularis propria was sampled by urologists
      and the sources of interpretive discrepancies among pathologists were studied in
      a community practice setting. MATERIALS AND METHODS: A total of 217 consecutive
      cases of urothelial neoplasm were independently reviewed by 3 pathologists. The
      presence or absence of muscularis propria as well as interpretive discrepancies
      were recorded. RESULTS: Despite clinical emphasis on accurate pathological
      staging portions of muscularis propria were absent from samples of histologically
      documented urothelial neoplasms in up to 51% of cases. Failure to obtain
      muscularis propria varied widely among urologists but was most often associated
      with cases of low grade papillary neoplasms, in which invasion is less likely.
      Muscularis propria was usually present in cases of noninvasive carcinoma in situ
      but this may have represented inadvertent sampling of structures in close
      proximity. The incidence of interpretive discrepancies among pathologists who are
      required to assess the status of muscularis propria was significant (24%). Almost
      all problems were related to artifacts and most may have been avoided if careful
      attention had been given to specimen sampling and processing. CONCLUSIONS: The
      well documented tendency toward cystoscopic under staging has not necessarily
      resulted in a high incidence of muscularis propria in bladder cases of urothelial
      neoplasms. Even when muscle may have been sampled, artifacts that were often due
      to thermocoagulation hampered accurate pathological staging.

PMID- 11992047
TI  - Treatment of carcinoma in situ with intravesical bacillus Calmette-Guerin without
      maintenance.
AB  - PURPOSE: Data concerning the relative efficacy of intravesical bacillus Calmette
      Guerin (BCG) on subgroups of carcinoma in situ of the bladder are limited. We
      report the outcome of primary carcinoma in situ and carcinoma in situ associated
      with Ta or T1 transitional cell carcinoma of the bladder treated with BCG.
      MATERIALS AND METHODS: Between 1987 and 1997, 135 patients (median age 70 years)
      with biopsy proven bladder carcinoma in situ underwent a standard course of 6 BCG
      instillations. Patients were divided into group 1-23 patients with primary
      carcinoma in situ, group 2-37 with carcinoma in situ associated with Ta
      transitional cell carcinoma and group 3-75 with carcinoma in situ associated with
      T1 transitional cell carcinoma. RESULTS: Median followup was 41 months. For
      groups 1 to 3, complete response rates at 3 months were 74% (17 of 23 cases), 70%
      (26 of 37) and 75% (56 of 75), respectively. The overall progression rates at 5
      years were 20% (3 of 15 cases), 18% (4 of 22) and 49% (25 of 51). Cancer specific
      survival rates were 83% (10 of 12 patients), 86% (12 of 14) and 59% (17 of 29),
      and the numbers of patients alive with the bladder intact were 60% (9 of 15), 58%
      (11 of 19) and 30% (12 of 40). Patients in group 3 treated with BCG had
      progression significantly earlier than those in groups 1 and 2 (log-rank test p =
      0.013). A complete response to BCG in group 3 patients significantly delayed time
      to progression (Cox regression p = 0.001) but did not reduce death from
      transitional cell carcinoma. Indeed, only 38% (8 of 21) of complete responders
      were alive with the bladder intact at 5 years. CONCLUSIONS: A single course of
      BCG is remarkably effective for primary carcinoma in situ and carcinoma in situ
      associated with Ta transitional cell carcinoma but is suboptimal in patients with
      carcinoma in situ associated with T1 transitional cell carcinoma. Better outcomes
      in each of the 3 groups may have occurred with maintenance BCG.

PMID- 11992048
TI  - Primary cisplatin, methotrexate and vinblastine chemotherapy with selective
      bladder preservation for muscle invasive carcinoma of the bladder: long-term
      followup of a prospective study.
AB  - PURPOSE: We evaluate the efficacy and bladder preservation rate of combined
      modality therapy consisting of deep transurethral resection of the primary
      bladder tumor followed by cisplatin, methotrexate and vinblastine chemotherapy in
      patients with muscle invasive transitional cell carcinoma of the bladder.
      MATERIALS AND METHODS: A total of 40 consecutive patients with clinical stage T2
      T4 NX M0 bladder cancer were included in the study and treated with transurethral
      resection followed by 3 courses of chemotherapy. Chemotherapy consisted of 100
      mg./m.2 cisplatin intravenously on day 1, 30 mg./m.2 methotrexate intravenously
      on days 1 and 8, and 4 mg./m.2 vinblastine intravenously on days 1 and 8
      administered every 21 days. Patients with disease in complete clinical remission
      after cycle 3 of therapy received 3 additional chemotherapy courses. Patients in
      whom complete clinical remission persisted after cycle 6 were closely followed
      with no further therapy until disease progression. RESULTS: A complete clinical
      remission was achieved in 21 patients (53%) after the first 3 cycles of therapy
      and a partial response occurred in 10 (25%), for an overall response rate of 78%
      (95% confidence interval [CI] 62% to 89%). With a median followup of 78 months
      (range 70 to 109) the estimated 7-year progression-free and overall survival
      rates were 40% (95% CI 25% to 55%) and 35% (95% CI 20% to 50%), respectively. The
      7-year survival rate with a functional bladder for complete clinical remission
      cases was 52% (95% CI 30% to 74%). Low grade, small tumor, absence of concomitant
      carcinoma in situ and response to therapy were all significant predictors for an
      increased probability of bladder preservation in univariate analysis. However,
      response to therapy was the only variable with independent prognostic value in
      the multivariate analysis (p = 0.002). CONCLUSIONS: Transurethral resection of
      bladder tumor followed by cisplatin, methotrexate and vinblastine chemotherapy
      results in long-term bladder preservation in a significant proportion of
      responding patients, and may be an acceptable alternative to radical surgery in
      select patients with muscle invasive bladder cancer.

PMID- 11992049
TI  - Brain metastases from bladder carcinoma: presentation, treatment and survival.
AB  - PURPOSE: We report the presentation of brain metastases from bladder carcinoma.
      We investigated the role of whole brain radiation therapy for treating this
      disease. MATERIALS AND METHODS: Between January 1982 and November 1999, 16
      patients with brain metastases from bladder carcinoma were treated at our
      institution. We reviewed patient and tumor characteristics at the time of the
      primary diagnosis and the brain metastasis diagnosis. We analyzed treatment
      results in regard to survival and local metastasis control. RESULTS: Brain
      metastases from bladder carcinoma were commonly accompanied by uncontrolled
      systemic metastases. Multiple brain lesions developed in 14 of the 16 patients.
      Of the 16 patients 14 received radiation therapy with or without surgery, 1 was
      treated surgically and 1 did not receive any treatment. The 11 patients treated
      with whole brain radiation therapy had a median survival of only 2 months (range
      0.5 to 11). A patient who received stereotactic radiosurgery survived 12 months
      after the brain metastasis diagnosis and 2 treated with radiation therapy after
      surgery survived 12.75 and 2.75 months, respectively (median 7.75). The patient
      treated with surgery alone survived 1.25 months after the brain metastasis
      diagnosis and 1 who received no treatment survived 1.75 months. Patients with
      multiple brain metastases had shorter survival than those with a single
      metastasis. CONCLUSIONS: Overall survival after brain metastasis development in
      patients with bladder carcinoma was poor. Although the number of patients in this
      study was small, results indicate that radiation therapy alone is inadequate
      treatment. Therefore, when possible, we advocate more effective treatment by
      combining radiation therapy with other treatment modalities, as recommended in
      ongoing clinical trials.

PMID- 11992050
TI  - Hereditary prostate cancer: clinical characteristics and survival.
AB  - PURPOSE: Hereditary prostate cancer accounts for 5% to 10% of all prostate cancer
      cases. We assessed clinical characteristics and survival in patients with
      hereditary prostate cancer MATERIALS AND METHODS: The study comprised 201
      patients from 62 Swedish hereditary prostate cancer families and 402 controls
      with prostate cancer who were matched for age and calendar year at diagnosis, and
      the hospital where the diagnosis was made. Clinical data were obtained from the
      National Cancer Registry, Causes of Death Registry and medical records. RESULTS:
      Median age at the diagnosis of hereditary prostate cancer was 68 years, which was
      6 years less than in patients with prostate cancer in the general population in
      Sweden. Distributions of tumor grade, symptoms at diagnosis and initial therapy
      were similar in hereditary prostate cancer cases and controls. More controls were
      classified with localized disease but it may have been due to methodological
      problems. Overall and cancer specific survival was similar in patients with
      hereditary prostate cancer and controls as well as in subgroup analyses including
      those with early onset and those diagnosed before 1990. Prostate cancer was the
      cause of death in 75% of patients with hereditary prostate cancer, in contrast to
      55% with prostate cancer in the Swedish population. This difference was
      completely explained by the earlier age at the diagnosis of hereditary prostate
      cancer. CONCLUSIONS: Hereditary prostate cancer has an earlier onset than
      sporadic prostate cancer but this study did not indicate any other important
      difference in clinical characteristics or survival in patients with hereditary
      prostate cancer and those with sporadic prostate cancer. However, it cannot be
      excluded that individual hereditary prostate cancer genes may have specific
      biological characteristics.

PMID- 11992051
TI  - Strategies combining total and percent free prostate specific antigen for
      detecting prostate cancer: a prospective evaluation.
AB  - PURPOSE: Determining total prostate specific antigen (PSA) in plasma can often
      identify men who are subsequently diagnosed with prostate cancer. However, excess
      false-positives create large financial and psychological burdens in prostate
      cancer screening. The percent free PSA is lower when prostate cancer is present,
      although to our knowledge no large prospective analyses to date have evaluated
      whether adding testing for free PSA may decrease false-positives, while
      maintaining or perhaps improving the detection of potentially curable tumors.
      MATERIALS AND METHODS: We measured total and percent free PSA in banked plasma
      samples from the Physicians' Health Study in 430 men who were later diagnosed
      with prostate cancer and 1,642 age matched controls who were not diagnosed with
      prostate cancer during a 12-year observation period. We calculated the number of
      cancers detected and the number of false-positives for various strategies of
      combined free and total PSA levels, and compared them to the use of total PSA
      alone. RESULTS: Total PSA with a cutoff of 4 ng./ml. detected 149 cases but also
      yielded 144 false-positives. A strategy that applied percent free PSA to men with
      total PSA 4 to 10 ng./ml. detected 133 to 140 cancers and decreased false
      positives to 83 of 117 depending on the percent free PSA cutoff used. As the
      percent free PSA cutoff was lowered from 25% to 20%, additional undetected
      cancers did not occur until year 9 of followup and the 20% cutoff decreased false
      positives and, thus, potential negative biopsies, by 42%. Percent free PSA was
      superior to total PSA for discriminating cases from controls within the total PSA
      range of 4 to 10 or 3 to 10 ng./ml. (p <0.0001). A percent free PSA cutoff of 20%
      in men with total PSA 3 to 10 ng./ml. detected 10% more cancers with 12.5% fewer
      false-positives than the conventional strategy of total PSA greater than 4
      ng./ml. Cancers missed by combined total and free PSA testing had longer
      intervals between blood sampling and diagnosis, and a greater likelihood of later
      diagnosis at an organ confined stage. CONCLUSIONS: These results demonstrate that
      in a prospective setting with long-term followup free PSA strategies can be
      identified that decrease unnecessary biopsies, while preserving or even improving
      cancer detection. Thus, total and free PSA can be combined without the need to
      weigh subjectively the trade-offs and relative costs of false-negative and false
      positive results.

PMID- 11992052
TI  - Serial biopsy results in prostate cancer screening study.
AB  - PURPOSE: We evaluated prostate biopsy results in men with elevated prostate
      specific antigen (PSA) levels and/or suspicious digital rectal examination whose
      initial biopsies did not reveal cancer. MATERIALS AND METHODS: A total of 2,526
      volunteers 40 years old or older underwent 1 or more prostate biopsies for serum
      PSA concentrations greater than 4.0 ng./ml. (before May 1995) or greater than 2.5
      ng./ml. (after May 1995), or digital rectal examination suspicious of cancer. We
      evaluated compliance with the biopsy recommendation and the cancer detection rate
      with regard to digital rectal examination results and increasing PSA levels.
      RESULTS: Of the men who underwent up to 10 biopsy procedures the serial cancer
      detection rates were 29%, 17%, 14%, 11%, 9% and 7%, respectively, on biopsy
      procedures 1 through 6. No significant difference in the yield of cancer on
      serial biopsies was observed between the groups using the greater than 4.0
      ng./ml. and greater than 2.5 ng./ml. cutoff. There was a trend for more cancers
      detected through serial screening to be organ confined compared with those
      detected on initial screening (78% versus 69%, p = 0.05). Also, more cancers
      detected using the greater than 2.5 ng./ml. cutoff were organ confined (80%
      versus 66%, p = 0.004). Only approximately 1% of the cancers fulfilled the
      published criteria for clinically insignificant tumors. CONCLUSIONS: Nearly a
      quarter of prostate cancers detected in this screening study were missed by the
      initial biopsy. Of the 962 prostate cancers detected 77% were detected with 1,
      91% with 2, 97% with 3 and 99% with 4 biopsy procedures. Serial biopsies detect
      more organ confined cancers without over detecting clinically unimportant tumors.
      Future studies are needed to determine whether obtaining more biopsy cores
      initially would provide earlier prostate cancer detection and avoid unnecessary
      repeat biopsies.

PMID- 11992053
TI  - Gleason score 7 prostate cancer on needle biopsy: is the prognostic difference in
      Gleason scores 4 + 3 and 3 + 4 independent of the number of involved cores?
AB  - PURPOSE: We addressed whether Gleason score 3 + 4 = 7 and 4 + 3 = 7 cancers on
      needle biopsy behave differently and whether this behavior is independent of the
      number of cores involved by cancer. If it is not an independent predictor of
      prognosis, one may report Gleason score 7 cancer with the number of positive
      cores without regard to whether the primary pattern was 3 or 4. This practice
      would remove a source of poor interobserver reproducibility when grading prostate
      cancer on needle biopsy. MATERIALS AND METHODS: We identified 537 patients with
      Gleason score 7 tumors on biopsy. The results of patient preoperative digital
      rectal examination, serum prostate specific antigen (PSA) measurement and age
      were used to predict 4 outcomes based on assessment of the corresponding radical
      prostatectomy specimens, including 1) pathological stage (organ confined, focal
      extraprostatic extension, nonfocal extraprostatic extension or seminal vesicle
      lymph node involvement), 2) organ confinement (yes/no), 3) Gleason score and 4)
      surgical margin status (positive/negative) RESULTS: Multivariate regression of
      postoperative Gleason score groups against all 5 input variables (3 + 4 versus 4
      + 3, number of positive cores, PSA, age and digital rectal examination) yielded a
      statistically significant positive correlation with preoperative PSA (p <0.001)
      and preoperative Gleason scores of 4 + 3 versus 3 + 4 on biopsy (p <0.001).
      Pathological stage correlated with preoperative PSA (p <0.001), Gleason score 4 +
      3 disease (p = 0.016), positive digital rectal examination (p <0.001) and 3 or
      more positive cores (p = 0.016). Positive surgical margins were predicted only by
      preoperative PSA (p = 0.001). CONCLUSIONS: Because the biological behavior of
      biopsy Gleason score 3 + 4 or 4 + 3 of Gleason score 7 cancer differs regardless
      of the number of cores involved, future nomograms predicting pathological stage
      would benefit from examining 3 + 4 and 4 + 3 disease separately.

PMID- 11992054
TI  - Prostate volume reduction with androgen deprivation therapy before interstitial
      brachytherapy.
AB  - PURPOSE: We assessed the degree of prostate downsizing using androgen
      deprivation, and determined its relation to clinical and pathological variables.
      MATERIALS AND METHODS: From June 1994 to January 2000, 107 patients with prostate
      cancer received androgen deprivation before interstitial brachytherapy at our
      hospital. All charts were reviewed for clinical, pathological and treatment
      related variables. Prostate volume was measured using transrectal ultrasound. All
      variables were analyzed with regard to the degree of prostate downsizing.
      RESULTS: Mean percent volume reduction of the prostate was 33% after a 3.7-month
      average duration of androgen deprivation. Larger prostate volume before androgen
      deprivation and longer deprivation duration statistically correlated with mean
      percent volume reduction. Simple linear and multiple regression analyses revealed
      that these 2 variables remained significant predictors of percent volume
      reduction. Subgroup analysis indicated that a significant difference was seen in
      patients who received androgen deprivation with luteinizing hormone releasing
      hormone agonists alone versus those who received treatment with total androgen
      blockade (luteinizing hormone releasing hormone agonists plus antiandrogens 30%
      versus 35%, p = 0.04), and when prostate volume before androgen deprivation was
      less than 50 cc versus larger volumes (30% versus 35%, p = 0.01). Of patients
      with an initial prostate volume of greater than 50 cc 82% achieved a volume of
      less than 50 cc after androgen deprivation therapy. CONCLUSIONS: Androgen
      deprivation therapy before brachytherapy is a method of downsizing the prostate
      to overcome anatomical limitations, including larger gland volume and pubic arch
      interference.

PMID- 11992055
TI  - What happens to testosterone after prostate radiation monotherapy and does it
      matter?
AB  - PURPOSE: There is uncertainty in the literature regarding the extent and
      relevance of temporary decreases in testosterone levels which occur after
      external radiation therapy for prostate cancer. We describe the phenomenon in
      detail and assess the impact on biochemical control and prostate specific antigen
      (PSA) doubling time in patients with relapse. MATERIALS AND METHODS: A total of
      666 men were followed after external beam radiation without neoadjuvant or
      adjuvant androgen ablation. Serial testosterone and PSA were measured before and
      at 3 to 6-month intervals after therapy. RESULTS: At a median nadir time of 6
      months testosterone decreased to an average of 83% of baseline. Of the patients
      7.5% experienced a decrease greater than 50%. All but 3% of those with normal
      initial testosterone levels experienced recovery to at least normal levels but
      only 60% had recovery to their individual pretreatment level. Multivariate
      analysis showed that patients with a low pre-intervention testosterone level, and
      those treated with larger radiation volumes had a lower testosterone nadir. In
      regard to biochemical control rates, initial testosterone level, degree of
      decrease, and absolute testosterone nadir had no effect in either univariate or
      multivariate analysis. PSA doubling times in patients with relapse were no
      different than in those with a small or larger testosterone decrease.
      CONCLUSIONS: Temporary testosterone decrease after radiation therapy to the
      prostate is a real phenomenon with no impact on subsequent tumor outcomes.

PMID- 11992056
TI  - Positive surgical margins after radical retropubic prostatectomy: the influence
      of site and number on progression.
AB  - PURPOSE: We assessed the effect of location and number of positive margins on
      biochemical progression in patients after radical retropubic prostatectomy for
      prostate cancer. MATERIALS AND METHODS: The incidence, location and number of
      positive surgical margins as well as recurrence and time to recurrence were
      evaluated in a consecutive series of 734 men who underwent radical retropubic
      prostatectomy for localized prostate cancer from 1992 through February 1999.
      RESULTS: Surgical margins were positive in 210 patients (29%), of whom 157 (75%)
      and 53 (25%) had 1 and more than 1 positive margin, respectively. Of the patients
      53 (25%) with tumor at any inked margin had biochemical recurrence. We identified
      no significant association of a particular location with biochemical recurrence.
      Bladder neck location did not carry an increased risk of recurrence (hazard ratio
      1.23, 95% confidence interval 0.54 to 2.80). However, these findings were made in
      a limited number of cases with positive bladder neck margins. Patients with more
      than 1 positive surgical margin were at increased risk for recurrence compared
      with those with a single positive surgical margin (hazard ratio 2.19, 95%
      confidence interval 1.11 to 4.32). In addition, prostate specific antigen greater
      than 20 ng./ml. and seminal vesicle invasion were significant predictors of
      progression. CONCLUSIONS: In patients with localized prostate cancer and positive
      surgical margins biochemical progression is not dictated by the specific location
      of a positive margin. However, multiple positive margins are associated with a
      significantly increased risk of biochemical recurrence. Longer followup and
      larger sample size are necessary to confirm these findings.

PMID- 11992057
TI  - Use of extended systematic sampling in patients with a prior negative prostate
      needle biopsy.
AB  - PURPOSE: We examine the potential impact of extended systematic biopsy schemes in
      patients with a prior negative prostate biopsy. MATERIALS AND METHODS: Between
      January 1999 and March 2001, 185 patients with a prior negative prostate needle
      biopsy underwent repeat biopsy. Systematic 10 core biopsies (sextant, lateral mid
      gland and lateral base) were performed in all patients. A subset of 111 patients
      underwent 6 additional biopsies directed anteriorly. All biopsy results were
      reviewed by a single pathologist. The overall and unique cancer detection rates
      were calculated for each biopsy site. McNemar's test was then used to compare the
      yield of various simulated biopsy schemes to define the optimal biopsy regimen.
      RESULTS: Overall, 67 of 185 patients (36%) were found to have cancer on repeat
      biopsy. The highest detection rate was found for the apex, lateral base and
      lateral mid sites. The mid lobar base site consistently yielded the lowest
      detection rate. These results were mirrored in the unique cancer detection rate
      calculations. The traditional sextant scheme detected only 73% of tumors. Using a
      lateral sextant scheme (apex, lateral mid gland and lateral base), the detection
      rate increased to 85% (p = 0.15). An 8 core biopsy scheme (apex, mid gland,
      lateral mid gland and lateral base) increased the detection rate to 95%. However,
      there was no significant increase in cancer detection rate when the 8 core scheme
      was compared to the 10 core scheme. The 6 anteriorly directed biopsies uniquely
      detected only 2 cancers. CONCLUSIONS: We recommend that patients with a prior
      negative prostate biopsy who are undergoing repeat biopsy receive at least an 8
      core biopsy scheme weighted toward the lateral aspect of the prostate.

PMID- 11992058
TI  - A comparison of multiple urine markers for interstitial cystitis.
AB  - PURPOSE: We measured several urine markers in 24-hour specimens from patients
      with interstitial cystitis and healthy controls. For each marker we determined
      whether the urine level was significantly different in interstitial cystitis and
      control cases, and whether the marker level correlated with the symptom score.
      MATERIALS AND METHODS: Study participants included 36 female patients with
      interstitial cystitis and 36 age matched female volunteers. Multiple urine
      aliquots were obtained to measure the various markers. RESULTS: Certain markers
      were significantly increased in interstitial cystitis, including anti
      proliferative factor, epidermal growth factor, insulin-like growth factor (IGF)
      binding protein-3 and interleukin (IL)-6. Markers significantly decreased in
      interstitial cystitis were heparin-binding epidermal growth factor-like growth
      factor, cyclic guanosine monophosphate and methylhistamine. Other markers were
      not significantly different in the interstitial cystitis and control groups,
      including total glycosaminoglycans, epitectin, hyaluronic acid, IL-8, IL-1 and
      nitrates plus nitrites. IGF-1 was undetectable in 24-hour urine samples but spot
      voided samples from the same interstitial cystitis population had IGF-1 levels
      similar to previously reported levels. The only significant association of marker
      with symptom score was a positive correlation of IL-6 with nocturia. For all
      markers the conclusions were the same whether the marker was normalized to
      creatinine or to 24 hours. CONCLUSIONS: This study confirmed several previously
      reported urine alterations in interstitial cystitis, including increased anti
      proliferative factor, epidermal growth factor, IGF binding protein-3 and IL-6,
      and decreased heparin-binding epidermal growth factor-like growth factor and
      cyclic guanosine monophosphate. Of all markers studied anti-proliferative factor
      had the least overlap in the interstitial cystitis and control groups, and so it
      is the most likely candidate to become a diagnostic test.

PMID- 11992059
TI  - Toward a precise definition of interstitial cystitis: further evidence of
      differences in classic and nonulcer disease.
AB  - PURPOSE: Interstitial cystitis is a bothersome condition in urological practice.
      There is continuous discussion on the extent and demarcation of this syndrome.
      Accumulated evidence indicates that interstitial cystitis is a heterogeneous
      syndrome. Today it is often divided into classic and nonulcer disease. Compared
      with classic interstitial cystitis the nonulcer type appears different in terms
      of demographic, endoscopic and histological findings as well as in the response
      to various types of treatment. However, in clinical series subdivision is not
      always performed, which makes it difficult to draw conclusions. We determined
      whether there are additional dissimilarities in clinical presentation in the 2
      subtypes of interstitial cystitis. MATERIALS AND METHODS: We evaluated 130
      patients with classic and 101 with nonulcer interstitial cystitis diagnosed
      according to National Institute for Diabetes and Digestive and Kidney Diseases
      criteria by surveying the clinical records, including voiding diaries. RESULTS:
      Patients with nonulcer disease were younger at diagnosis (p <0.0001) and at
      symptom onset. Furthermore, there was a marked and significant difference in
      bladder capacity while patients were under general anesthesia (p <0.0001).
      CONCLUSIONS: The current findings together with previous findings clearly
      demonstrate that the 2 subtypes of interstitial cystitis represent separate
      entities. We suggest refining the National Institutes of Health-National
      Institute for Diabetes and Digestive and Kidney Diseases criteria, so that
      subtyping scientific materials is considered mandatory, hence, ensuring that the
      2 subtypes are evaluated separately in clinical studies.

PMID- 11992060
TI  - Retroperitoneoscopic lymphatic management of intractable chyluria.
AB  - PURPOSE: We present our experience with retroperitoneoscopic lymphatic
      disconnection for the treatment of patients with intractable chyluria and review
      the current literature. MATERIALS AND METHODS: Our study included 6 males and 3
      females 22 to 55 years old who presented with intractable chyluria of filarial
      origin and variable duration (2 to 11 years), and were selected for
      retroperitoneoscopic management of 11 renoureteral units. Diagnosis was based on
      urine examination for the presence of chyle and fat globules, cystoscopy,
      excretory urogram and retrograde ureteropyelography. The technique of
      retroperitoneoscopic management of chyluria consisted of nephrolympholysis,
      ureterolympholysis, hilar vessel stripping, fasciectomy and nephropexy. The first
      3 procedures were done in all cases, whereas fasciectomy was only done in 4 cases
      and nephropexy in 3 as required. RESULTS: Chyluria disappeared in all ipsilateral
      renal units of the patients who underwent retroperitoneoscopic management but it
      recurred in 2 patients at 1 and 9 months of followup from the contralateral side.
      Both cases have since been successfully treated with contralateral
      retroperitoneoscopic management. Complications included lymphatic leak through
      the drain which persisted for 5 days in 1 case and an inadvertent clipping of a
      branch of the posterior segmental artery of the kidney in 1. The latter patient
      did not have pain or hypertension and the renal scan did not reveal any focal
      deficit at followup. All patients were followed periodically from 6 months to
      41/2 years (mean of 31 months). CONCLUSIONS: The objectives of open surgical
      treatment of intractable chyluria can be achieved by the minimally invasive
      retroperitoneoscopic technique. Nephrolympholysis, ureterolympholysis and
      stripping of hilar vessels were essential in all cases. Fasciectomy and
      nephrectomy were done in a few patients and as mentioned are not recommended
      routinely. This approach has all of the benefits of laparoscopic surgery without
      compromising the principles of open surgery. Retroperitoneoscopic management was
      safe, effective and efficient.

PMID- 11992061
TI  - UroLume stents: lessons learned.
AB  - PURPOSE: The UroLume (American Medical Systems, Minnetonka, Minnesota)
      endoprosthesis has been commercially available since 1990 and has been advocated
      for use in men with urethral stricture disease and detrusor-sphincter dyssynergia
      due to spinal cord injury. Despite reports of its success and ease of removal, we
      have noted management problems in several complex cases. MATERIALS AND METHODS:
      We retrospectively analyzed the outcome of 10 men who required several additional
      procedures or experienced complications following UroLume placement. RESULTS: Of
      the patients 4 had detrusor-sphincter dyssynergia and 6 had urethral stricture
      disease. All patients with detrusor-sphincter dyssynergia required
      hospitalization for management of urosepsis within 4 to 10 months of stent
      placement, and all 4 experienced stent migration requiring placement of a tandem
      stent (3), bladder neck resection (3) or sphincterotomy (1). Two men were in
      retention following placement of a second stent and required stent explantation.
      Of the other 6 men 2 had bulbar and 3 had membranous urethral disease, and 1 had
      a severe bladder neck contracture following radical retropubic prostatectomy.
      Strictures recurred within the stent lumen in all 6 men and/or adjacent to it in
      3. At least 1 repeat procedure was required in all 6 men (within 6 months in 5),
      and 1 experienced significant bleeding during open explantation which required
      perineal urethrostomy. CONCLUSIONS: In our referral experience stent migration
      and recurrent stenosis were noted following UroLume insertion. Placement of a
      tandem stent was associated with urethral obstruction. In many cases these
      adverse outcomes may be secondary to improper patient selection. Therefore,
      judicious use of the UroLume stent and proper case selection are essential since
      stent removal is not always straightforward.

PMID- 11992062
TI  - Double forced sling by combining in situ vaginal wall and Infast pubic bone
      suburethral stabilization techniques: a new method.
AB  - PURPOSE: We evaluated the results and effectiveness of the double forced sling by
      combining in situ vaginal wall and Infast (Influence, Inc., San Francisco,
      California) pubic bone suburethral stabilization techniques as a new method.
      MATERIALS AND METHODS: The new technique was used in 40 patients, of whom 32
      completed 2 years of followup. Previous surgery included hysterectomy in 8 cases,
      anterior and posterior vaginal wall repair in 6, and 1 or 2 incontinence
      procedures in 24. Types 2, 3 and mixed incontinence were diagnosed in 12, 12 and
      8 patients, respectively. With this technique a gelatin coated synthetic sling
      was fixed to the previously prepared vaginal sling surface with watertight
      stitches to create a doubled forced sling, which was fixed to the pubic bone with
      2 screws using an Infast inserter. Patient outcomes were evaluated by
      questionnaire analysis and the pad test. RESULTS: The cure, improvement and
      failure rates were 81.25%, 6.25% and 12.5% in the 32 patients who completed 2
      years of followup. Surprisingly successful results were achieved in all 24
      secondary cases. Moderate cystocele in 4 patients and rectocele in 8 were
      corrected simultaneously. Temporary urinary retention in 4 patients resolved in 2
      weeks. Of the 32 patients 28 reported that they would repeat the procedure and
      recommend it to others. CONCLUSIONS: The double forced sling has 2 advantages
      that make it superior to other techniques, namely a minimal complication rate and
      enhanced support accomplished by an easy and noninvasive technique.

PMID- 11992063
TI  - Prostate specific antigen predicts the long-term risk of prostate enlargement:
      results from the Baltimore Longitudinal Study of Aging.
AB  - PURPOSE: Prostate specific antigen (PSA) is a predictor of prostate growth in men
      with lower urinary tract symptoms. The long-term risk of prostate enlargement as
      a function of PSA among community dwelling volunteers is unknown. MATERIALS AND
      METHODS: A Cox proportional hazards regression model was used to study the
      relationship between baseline PSA level at ages 40 to 49.9 years in 194 men, 50
      to 59.9 in 191 and 60 to 69.9 in 144, and prostate enlargement, defined as a
      prostate volume larger than the 75th percentile for age decade, as measured by
      magnetic resonance imaging in a longitudinal study of aging (Baltimore
      Longitudinal Study of Aging, National Institute on Aging). Kaplan-Meier survival
      analysis was performed to estimate the probability of freedom from prostate
      enlargement with time as a function of baseline PSA level. RESULTS: The relative
      risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old
      with a baseline PSA of 0.31 ng./ml. or more compared to men with PSA levels of
      0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in
      men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing
      men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those
      with PSA 0.50 or less. The cumulative probability of freedom from prostate
      enlargement at 20 years was 0.89 (95% confidence interval ([CI] 0.79-0.99) and
      0.63 (0.52-0.74) for men 40 to 49.9 years old with PSA levels below and above
      0.30 ng./ml., respectively. For men 50 to 59.9 years old the 10-year probability
      of freedom from prostate enlargement was 0.90 (95% CI 0.84-0.96) and 0.59 (0.43
      0.74) when PSA levels were below and above 0.80 ng./ml., respectively. At age 60
      to 69.9 years the 10-year probability of freedom from prostate enlargement was
      0.83 (95% CI 0.72-0.93) and 0.27 (0.09 to 0.48) when PSA levels were below and
      above 1.70 ng./ml., respectively. CONCLUSIONS: These data demonstrate the long
      term risk of prostate enlargement by PSA level. Risk stratification based on PSA
      level may be useful to identify men at greatest risk for adverse events due to
      prostate enlargement and selection of men for future benign prostatic hyperplasia
      studies.

PMID- 11992064
TI  - Clinical predictors in the use of finasteride for control of gross hematuria due
      to benign prostatic hyperplasia.
AB  - PURPOSE: We identify predictors of clinical response as well as response time in
      patients treated with finasteride for gross hematuria due to benign prostatic
      hyperplasia. MATERIALS AND METHODS: A retrospective chart review was preformed of
      53 patients who had been given 5 mg. finasteride daily for the treatment of
      active bleeding or a recent history of recurrent bleeding. Urological evaluations
      were negative for tumor in all patients. A history of prostatectomy,
      anticoagulant status and prostate size was determined. The degree of hematuria
      was then graded before and after finasteride treatment according to our
      previously described system. Of the 53 patients who were actively bleeding at
      initial evaluation 16 were followed to determine time required for complete
      resolution of hematuria. RESULTS: Hematuria grade improved after finasteride in
      50 (94%) patients. Overall 77% of patients (41 of 53) experienced no further
      bleeding while taking finasteride. Mean followup was 38 months (range 3 to 86).
      Of the patients 86% (12 of 14) taking coumadin, 77% (10 of 13) taking aspirin and
      73% (19 of 26) on no anticoagulants had no further bleeding once on finasteride.
      Of the patients who had undergone prior transurethral prostatectomy 84% (26 of
      31) experienced no further bleeding versus 68% (15 of 22) of those who had not
      undergone previous surgery. In the 16 patients who began finasteride while
      actively bleeding the average time to clear urine was 12 days (range 2 to 45).
      Prostatic volume correlated with the average time needed for resolution of
      hematuria, which was 2.7 days or longer for small (less than 40 gm.), 10.3 days
      or longer for large (40 to 100), 19 days or longer for extra large (100 to 150)
      and 45 days or longer for extra extra large (greater than 150) glands. Hematuria
      resolved an average of 5.5 days versus 18.6 days in those who had or had not
      undergone previous prostatectomy, respectively. CONCLUSIONS: Our long-term
      followup demonstrates finasteride as a useful treatment for benign prostatic
      hyperplasia related gross hematuria, which is effective in patients who are on
      anticoagulants. In patients with larger prostatic volumes a longer time to
      response and higher incidence of recurrent but lower grade bleeding should be
      anticipated compared to those who have undergone prior prostatectomy or have a
      smaller prostate.

PMID- 11992065
TI  - Urodynamic effects of terazosin treatment for Japanese patients with symptomatic
      benign prostatic hyperplasia.
AB  - PURPOSE: For treating benign prostatic hyperplasia (BPH) 5 or 10 mg. terazosin
      hydrochloride daily has been routinely used in North America and Europe. We
      investigated the urodynamic effects of 2 mg. terazosin daily on Japanese patients
      with symptomatic BPH using pressure flow study. MATERIALS AND METHODS: A total of
      20 Japanese patients 50 years old or older with symptomatic BPH underwent
      symptomatic and urodynamic evaluations, including pressure flow study, before and
      after terazosin treatment. Patients were given 1 mg. terazosin once daily for the
      first 7 days and they continued to receive 1 mg. terazosin twice daily for the
      following 3 weeks. RESULTS: At 4 weeks after terazosin treatment the
      International Prostate Symptom Score, quality of life index and maximum and
      average flow rates were significantly improved. Pressure flow study demonstrated
      decreased detrusor pressure at maximum flow, and minimum detrusor pressure during
      voiding and urethral resistance factor after terazosin treatment. Of the 20
      patients 13 (65%) showed improvement in the linear passive urethral resistance
      relation. There was no significant difference in the maximum W. factor before and
      after terazosin treatment. CONCLUSIONS: Terazosin treatment, even 2 mg. daily,
      urodynamically relieved bladder outlet obstruction in Japanese patients with
      symptomatic BPH without any changes in detrusor contractility.

PMID- 11992066
TI  - Transurethral microwave therapy in 200 patients with a minimum followup of 2
      years: urodynamic and clinical results.
AB  - PURPOSE: We investigated the long-term efficacy of the second generation Targis
      thermotherapy device (Urologix, Inc., Minneapolis, Minnesota) for decreasing
      outflow obstruction caused by benign prostatic hyperplasia. MATERIALS AND
      METHODS: At a minimum followup of 24 months 200 patients with bladder outlet
      obstruction documented on urodynamics and cystoscopy document with preserved
      detrusor function underwent transurethral microwave therapy while under local
      anesthesia. In 45% of cases the general American Society of Anesthesiologists
      health score was 3 or greater. RESULTS: After a median observation time of 42
      months (range 2 to 72) 43 patients (22%) who required additional treatment
      (repeat thermotherapy, transurethral prostate resection or permanent cystostomy)
      were excluded from further analysis, as were 15 (7.5%) who died of causes
      unrelated to treatment during followup and 13 (6.5%) who were lost to followup or
      refused followup investigations. In the 162 patients evaluated 6 months after
      treatment the median International Prostate Symptom Score decreased from 23
      points (range 10 to 34) before treatment to 3 (range 0 to 21) and remained stable
      at 12 and 24 months. Median maximum flow increased from 6 ml. per second (range 1
      to 15) before treatment to 14.5 (range 4 to 50) 6 months after treatment and
      remained stable at 12 and 24 months. Median post-void residual urine volume
      decreased from 170 ml. (range 35 to 720) before treatment to 17 (range 0 to 327)
      after 6 months and then remained unchanged. Urodynamic evaluation in the 162
      patients after 6 months showed a decrease from pretreatment median detrusor
      opening pressure of 87.5 to 53 cm. water. Median detrusor pressure at maximum
      flow decreased from 86 to 58 cm. water 6 (p <0.0001). At the 24-month followup 59
      of the 129 evaluable patients agreed to undergo repeat urodynamic evaluation.
      Pressure flow analysis in these 59 cases revealed a decrease in median minimal
      urethral opening pressure from 70 to 40 cm. water at 6 months and to 38 cm. water
      at 24 months (p <0.0001). Median detrusor pressure at maximum flow decreased
      significantly from the pretreatment value of 86 to 55 cm. water at 6 months and
      58 cm. water at 24 months (p <0.0001). CONCLUSIONS: In patients with a good
      initial response to treatment, which is achieved in approximately 80%,
      transurethral microwave therapy provides excellent long-term subjective and
      objective results. Improved urinary flow, decreased post-void residual urine
      volume and urodynamic parameters remain stable at 2 years. Transurethral
      microwave therapy with second generation microwave equipment did not compromise
      any conventional treatment needed in the 22% of patients who were nonresponders
      at 6 months.

PMID- 11992067
TI  - Mechanical failure of the American Medical Systems Ultrex inflatable penile
      prosthesis: before and after 1993 structural modification.
AB  - PURPOSE: The 700 Ultrex (American Medical Systems, Minnetonka, Minnesota) is the
      only penile prosthesis capable of length and girth expansion. Early experience
      with the 700 Ultrex showed an increased mechanical failure rate compared with the
      700CX, mostly secondary to cylinder failure. In 1993 the Ultrex cylinders were
      modified. We examined the performance of the Ultrex device before and after
      modification. MATERIALS AND METHODS: We compared our results with the Ultrex
      prosthesis before (group 1) and after (group 2) the 1993 modification. We
      implanted 239 devices from October 1989 to December 1999. A total of 26 patients
      have died. Followup was obtained on the results of 137 of the remaining 213
      implants (64%), including 85 pre-modification devices in 85 patients and 52 post
      modification devices in 51, via a mailed questionnaire, telephone survey or chart
      review. The questionnaire and survey included a 5-point satisfaction scale.
      Groups 1 and 2 were compared in regard to 3 end points, namely cylinder,
      mechanical and overall failure. RESULTS: Followup was less than 1 to 136 months
      (median 92, 25th to 75th percentiles 43 to 108) in group 1 and less than 1 to 92
      months (median 46, 25th to 75th percentiles 21 to 75) in group 2. The 5-year
      Kaplan-Meier estimates of overall, mechanical and cylinder survival in groups 1
      and 2 were 64.7%, 70.7% and 80.2%, and 77.7% (p = 0.23), 93.7% (p = 0.017) and
      96.2% (p = 0.008), respectively. Overall satisfaction was similarly high in
      groups 1 and 2 (mean 3.9 and 4 points). CONCLUSIONS: On long-term followup the
      1993 modification of the Ultrex cylinders appears to have significantly decreased
      the propensity of cylinder failure of the pre-modification device.

PMID- 11992068
TI  - Patient satisfaction with the outcome of surgery for urethral stricture.
AB  - PURPOSE: We assessed patient satisfaction with the outcome of surgery for
      urethral strictures and compared it with objective clinical data. MATERIALS AND
      METHODS: A total of 267 consecutive patients who underwent surgery for urethral
      stricture between March 1993 and December 1999 were questioned regarding
      satisfaction. Mailed questionnaires or a telephone interview, if questionnaires
      were not returned, provided information on the urinary tract, voiding, sexual
      function, overall satisfaction and miscellaneous impairments after surgery for
      urethral strictures. The response rate was 87% (233 of 267 patients). Subjective
      data were compared with objective clinical findings. RESULTS: Of the 203 patients
      who underwent successful urethroplasty 159 (78%) and 24 of the 30 (80%) in whom
      urethroplasty was considered a failure from the physician viewpoint were
      satisfied or very satisfied with the outcome of urethral surgery. Patients who
      underwent re-intervention for complications other than re-stricture and those who
      complained of a weak or very weak urinary stream were considerably less
      satisfied. Factors influencing sexual function also had an important impact on
      patient satisfaction. Patients with marked or severe penile curvature, penile
      shortening, erection deterioration and a markedly or severely impaired sexual
      life were especially dissatisfied. CONCLUSIONS: Patients consider the outcome of
      surgery for urethral strictures differently than physicians. The outcome of
      urethroplasty should be assessed not only by objective, but also by subjective
      criteria. Patients need appropriate preoperative counseling. With realistic
      expectations most men are satisfied with surgery for urethral stricture.

PMID- 11992069
TI  - Repair of a diaphragmatic injury during hand assisted laparoscopic nephrectomy
      using an onlay patch of polypropylene and polyglactin mesh.
AB  - PURPOSE: We describe a simple and time efficient technique for repairing a
      diaphragmatic injury occurring during right hand assisted laparoscopic radical
      nephrectomy. MATERIALS AND METHODS: A dual layer polypropylene and polyglactin
      mesh was created extracorporeally by sewing a 2 x 2 piece of polypropylene mesh
      to a 2 x 2 piece of polyglactin mesh with 4, 4-zero interrupted polyglactin
      sutures. This dual layer was then positioned manually over the diaphragmatic rent
      and secured with a laparoscopic stapling device. A 16Fr chest tube was placed at
      the conclusion of the procedure. RESULTS: Overall operative time was 3.5 hours
      with an estimated blood loss of 100 cc. Repair of the diaphragmatic injury
      extended operative time by 25 minutes. Extubation was done at the conclusion of
      the case and the chest tube was removed within 36 hours of the procedure. The
      patient was discharged home on postoperative day 3. At 14 months of followup the
      patient remained disease-free on radiography and without pulmonary or
      gastrointestinal sequelae. CONCLUSIONS: We describe a simple and time efficient
      technique for repairing diaphragmatic injury occurring during right hand assisted
      laparoscopy. This technique takes advantage of the manual and tactile sensation
      provided by the hand assistance device, provides a tension-free repair and avoids
      laparoscopic suturing.

PMID- 11992070
TI  - Ectopic adrenocorticotropic hormone production by a noncatecholamine secreting
      pheochromocytoma.

PMID- 11992071
TI  - Unusual presentation of acute renal failure from obstructive uropathy.

PMID- 11992072
TI  - Percutaneous management of renal artery aneurysm with a stent-graft.

PMID- 11992073
TI  - Migration of arterial embolization coils as nidus for renal stone formation.

PMID- 11992074
TI  - Origin of urothelial carcinoma after renal transplant determined by fluorescence
      in situ hybridization.

PMID- 11992075
TI  - Lymphoepithelioma-like carcinoma of the bladder.

PMID- 11992076
TI  - The chronic pelvic pain syndrome after brachytherapy for carcinoma of the
      prostate.

PMID- 11992077
TI  - Metastatic carcinoid tumor of the prostate.

PMID- 11992078
TI  - Laparoscopic prostatectomy with vascular control for benign prostatic
      hyperplasia.

PMID- 11992079
TI  - Transverse fibrous bar in prostatic urethra after transurethral prostatectomy.

PMID- 11992080
TI  - Re: Penile incarceration with barbell retaining ring.

PMID- 11992081
TI  - The insulin-3 gene: lack of a genetic basis for human cryptorchidism.
AB  - PURPOSE: The etiology of cryptorchidism appears to be multifactorial and related
      to hormonal and mechanical factors. Recently, the insulin-3 gene (INSL3) was
      noted to have a role in mouse gubernacular development and testicular descent.
      Knockout male mice for the INSL3 gene show isolated bilateral cryptorchidism.
      This phenotype suggests that INSL3 may have a role in the development of human
      cryptorchidism. Using single strand conformational polymorphism analysis we
      detected mutations of the INSL3 gene in boys with cryptorchidism. MATERIALS AND
      METHODS: Genomic DNA from 118 boys with cryptorchidism and 48 normal controls
      were obtained from 3 institutions. Using polymerase chain reaction with INSL3
      sequence specific primers DNA fragments were analyzed using single strand
      conformational polymorphism reactions. Samples with band shifts were re-amplified
      and sequenced to detect mutations. RESULTS: A single base substitution (G greater
      than A) causing an amino acid change (missense mutation) was identified in 27 of
      118 cryptorchid (23%) samples and 12 of 48 normal (25%) samples. Two other base
      substitutions did not produce alterations in the amino acid sequence (silent
      mutations). CONCLUSIONS: Although a common polymorphism was detected in the INSL3
      gene, no specific mutations were detected in a large population of individuals
      with cryptorchidism. Therefore, mutations in the coding region of the INSL3 gene
      are not a common cause of human cryptorchidism.

PMID- 11992082
TI  - Metachronous presentation of ureterovesical junction obstruction contralateral to
      a multicystic dysplastic kidney.

PMID- 11992083
TI  - Combined endoscopic resection and brachytherapy for recurrent intrapelvic Wilms
      tumor.

PMID- 11992084
TI  - Metastatic Crohn's disease involving the genitalia.

PMID- 11992085
TI  - Blunt traumatic hematuria in children. Is a simplified algorithm justified?
AB  - PURPOSE: We determined whether radiographic evaluation is indicated in all
      children with traumatic hematuria. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 110 children from 1992 to 1999 diagnosed with blunt
      trauma and hematuria. It is routine practice at our emergency department to
      perform radiographic evaluation in all children with hematuria regardless of the
      degree. Each chart was evaluated for the mechanism of injury, degree of
      hematuria, hypotension, imaging studies, renal injury, renal anomalies,
      associated injuries and outcome. RESULTS: A total of 110 patients 1 to 18 years
      old (mean age 9) were identified. The most common mechanism of injury was motor
      vehicle accident in 37 children (34%), followed by a fall in 32 (29%). Grades I
      to V renal injury was present in 5, 6, 6, 6 and 1 cases, respectively (22%),
      while 1 (0.9%) involved ureteropelvic junction avulsion. No child had renal
      pedicle injury. In 9 patients renal anomalies were detected incidentally. Of the
      110 patients 101 underwent radiographic evaluation, including computerized
      tomography in 97 (88%). The 24 patients (22%) with significant renal injury and
      all with incidentally diagnosed renal anomalies had 50 or greater red blood cells
      per high power field on urinalysis, while 1 with ureteropelvic junction avulsion
      presented without hematuria. Hypotension was present in only 3 patients (2.7%),
      who also had associated injuries, including 2 who presented with renal injury.
      All 3 with associated injuries. Associated injuries were identified in 11 of 25
      patients (44%). The 9 patients (8%) who did not undergo radiographic imaging had
      negative results on repeat urinalysis with an excellent outcome. CONCLUSIONS: We
      recommend that radiological evaluation consisting of abdominal and pelvic
      computerized tomography should be performed only in patients with 50 or greater
      red blood cells on urinalysis, hypotension at presentation to the emergency room
      or based on the severity of mechanism of injury, for example high speed motor
      vehicle accident deceleration injuries. The patient who presented with
      ureteropelvic junction avulsion without hematuria would have undergone imaging
      considering the mechanism of injury and number of associated injuries.

PMID- 11992086
TI  - Renal outcome in patients with cloaca.
AB  - PURPOSE: Cloaca is a complex malformation in which the rectum, vagina and urinary
      tract open into a single common channel. Functional results after reconstructive
      surgery have been documented but the renal outcome is less clearly understood.
      MATERIALS AND METHODS: The records of all patients with cloacal malformation
      treated at our institution from 1980 to 2000 were retrospectively reviewed to
      determine the renal outcome. All patients underwent serial ultrasound of the
      urinary tract, voiding cystography, nuclear renography, lumbosacral radiography,
      and measurement of serum creatinine and glomerular filtration rate when
      appropriate. RESULTS: We identified 64 patients 0.5 to 19 years old (mean age
      11.2) at the time of the study. Of the 64 patients 53 (83%) were born with a
      structural abnormality of the urinary tract, including renal dysplasia in 17
      (27%), ectopic kidney in 9 (14%), solitary kidney in 8 (13%), duplex kidneys in 6
      (9%) and ureteropelvic junction obstruction in 3 (5%). Vesicoureteral reflux was
      noted in 34 cases (53%) and a sacral abnormality was diagnosed in 36 (57%). The
      glomerular filtration rate was measured in 38 patients (60%). Chronic renal
      failure developed in 32 patients (50%) with a glomerular filtration rate of less
      than 80 ml. per minute per 1.73 m.2, including 11 (17%) who progressed to end
      stage renal failure, 4 who (6%) required renal transplantation and 4 who died of
      chronic renal failure. Of the 32 children with a glomerular filtration rate of
      less than 80 ml. per minute per 1.73 m.2 44% had renal dysplasia, 25% had a
      solitary kidney, 44% had sacral anomalies, 72% had vesicoureteral reflux and 47%
      had secondary renal scarring. CONCLUSIONS: Renal impairment causes significant
      morbidity and mortality in patients with a cloacal malformation. These patients
      need a complete nephrourological assessment in the neonatal period due to the
      high incidence of urinary tract and sacral anomalies as well as careful post
      reconstruction followup.

PMID- 11992087
TI  - Influence of enterocystoplasty on linear growth in children with exstrophy.
AB  - PURPOSE: Many children with bladder exstrophy undergo reconstruction
      incorporating bowel into the lower urinary tract, which may result in metabolic
      changes affecting height. Linear growth in children with exstrophy who underwent
      enterocystoplasty was studied. MATERIALS AND METHODS: We retrospectively reviewed
      the charts of children with classic bladder exstrophy who underwent bladder
      augmentation with small or large bowel, or creation of a bowel neobladder before
      age 11 years. Mean followup plus or minus standard error was 9.4 +/- 0.9 years.
      Most patients were assessed yearly with measurement of height and serum
      electrolytes. Metabolic acidosis was treated with oral bicarbonate. Preoperative
      height percentiles at enterocystoplasty were compared to height percentiles at
      the most recent visit. In addition, height percentiles in a control group of
      individuals with exstrophy who did not undergo enterocystoplasty were compared to
      postoperative height percentiles in the enterocystoplasty group. The t test was
      used for statistical analysis. RESULTS: Data on 18 children who underwent bladder
      reconstruction with bowel were compared with those on a control group of 18 with
      exstrophy. The mean preoperative height percentile at a mean age of 5.2 years was
      35.6 +/- 4.5 and the postoperative height percentile at a mean age of 14.6 years
      was 20.3 +/- 5.7 (p <0.01). The mean height percentile in the control group at a
      mean age of 15.2 years was 30.6 +/- 7.8 (p <0.01 versus the postoperative height
      percentile in the study group. In the enterocystoplasty group 2 patients were
      receiving oral bicarbonate for metabolic acidosis. Five patients who underwent
      enterocystoplasty and 6 controls were below the third percentile for height.
      CONCLUSIONS: In children with bladder exstrophy bladder augmentation or
      neobladder creation may have an adverse effect on linear growth. The height of
      children with bladder exstrophy is less than average compared with standard
      growth charts.

PMID- 11992088
TI  - Early hospital discharge for intravesical ureteroneocystostomy.
AB  - PURPOSE: Inpatient stays of 3 to 5 days are common in the surgical management of
      vesicoureteral reflux and often include the use of bladder catheters, ureteral
      stents and perivesical drains. We reviewed our recent experience, in which
      patients undergoing routine ureteroneocystostomy were often discharged home on
      postoperative day 1 to determine the safety and efficacy of our management.
      MATERIALS AND METHODS: Between July 1998 and March 2001 patients who underwent
      intravesical ureteroneocystostomy at 2 major tertiary care institutions were
      identified. Patients who also underwent simultaneous additional operative
      procedures, bilateral ureteral duplication or ureteral tapering were excluded
      from study. Data recorded included patient demographics, the procedure, operative
      and postoperative pain, nausea and bladder spasm management, hospital stay, post
      hospital discharge problems and operative success. RESULTS: Of the 113 patients
      with complete data available for analysis 101 received ketorolac postoperatively,
      including 75 females and 26 males with a mean age of 5.01 years (range 6 weeks to
      16 years). There were 67 bilateral and 34 unilateral reimplantations. No ureteral
      stents or perivesical drains were placed. A perioperative urethral Foley catheter
      was removed on postoperative day 1 in all except 3 cases. Caudal analgesia with
      0.25% bupivacaine before or after the operation was given in 91% of cases as a
      single injection. Epidural catheters were not used. In the ketorolac group
      average hospitalization was 29.5 hours (range 14 to 72). Of the 101 patients 58%
      were discharged home within 24 hours (average 21.3) and a further 11% were
      discharged home within 36 hours (average 27.4). All except 4 patients (4%) were
      discharged home within 48 hours of surgery. In the 12 patients who did not
      receive ketorolac average hospital stay was 43.8 hours (p <0.001). Gender did not
      affect the duration of hospitalization. Patients younger than 1 or older than 5
      years old had a longer hospital stay than children between 1 and 5 years old
      (average 32.8 versus 25.5 hours). All patients received anticholinergics. The 9
      complications (8%) involved urinary tract infection in 3 cases, and persistent
      nausea and vomiting, medication reaction and reoperation for clot evacuation in 1
      each. Postoperatively 3 patients had persistent refluxing ureters. CONCLUSIONS:
      Routine surgical repair of vesicoureteral reflux can be successful with early
      bladder catheter removal and without stents or drains, necessitating only
      overnight hospitalization in the majority of patients. Ketorolac can be given
      safely in children with minimal risk and when combined with caudal analgesia it
      facilitates early discharge home.

PMID- 11992089
TI  - Impact of prenatal diagnosis on the morbidity associated with ureterocele
      management.
AB  - PURPOSE: We postulated that prenatal detection of ureteroceles has a positive
      impact on the natural history and clinical outcome of ureteroceles in duplex
      system. MATERIALS AND METHODS: Between 1992 and 2000, 95 children underwent
      surgery for a ureterocele in a duplex system. We evaluated the impact of prenatal
      diagnosis in 40 cases versus postnatal diagnosis in 55 on morbidity, as measured
      by postoperative urinary tract infection and secondary procedures, while
      controlling for ureterocele type and the initial surgical approach. RESULTS: Mean
      followup in the 2 groups was 3.9 years. Preoperatively the reflux rate was 51% in
      the prenatal and 66% in the postnatal groups. Preoperatively urinary tract
      infections were less common in the prenatal group (12% versus 84%). Mean age at
      initial intervention in prenatally and postnatally diagnosed patients was 6 and
      31 months, respectively. Postoperatively the urinary tract infection rate was
      double in postnatally diagnosed patients. Overall postoperatively reflux was
      similar in the 2 groups and grades III to V reflux with urinary tract infection
      accounted for 14 of the 21 secondary bladder procedures (67%). After initial
      endoscopic decompression none of the prenatally diagnosed patients with
      intravesical ureteroceles required reoperation, whereas 6 (50%) with extravesical
      ureteroceles required reoperation. All 10 prenatally diagnosed extravesical
      ureteroceles treated with partial nephrectomy were cured. Overall the secondary
      procedure rate in the postnatal group was higher than in the prenatal group (46%
      versus 20%, p = 0.02). Also, there was a difference in the reoperation rate in
      the endoscopic decompression group according to mode of presentation (p = 0.03)
      and a difference when comparing endoscopic treatment with partial nephrectomy in
      all patients (p = 0.02). CONCLUSIONS: Prenatal diagnosis decreases morbidity and
      potential adverse outcomes related to infection. Overall prenatal diagnosis is
      associated with a decreased rate of secondary procedures independent of the type
      of ureterocele. Prenatally diagnosed intravesical ureteroceles may be cured by
      endoscopic incision alone but for extravesical ureteroceles partial nephrectomy
      appears to be more definitive.

PMID- 11992090
TI  - Vesicoureteral reflux and ureteropelvic junction obstruction in children with
      horseshoe kidney: treatment and outcome.
AB  - PURPOSE: Horseshoe kidney is the most common renal fusion anomaly. We determined
      the treatment and outcome of vesicoureteral reflux and ureteropelvic junction
      obstruction in children with horseshoe kidney. MATERIALS AND METHODS: We reviewed
      the medical and radiological records of 52 consecutive children, including 32
      boys and 20 girls, in whom horseshoe kidney was diagnosed at 2 children's
      hospitals during 1990 to 1999. Patient age at diagnosis was 1 day to 12 years
      (mean 3.9 years). In 2 children with horseshoe kidney neuropathic bladder was
      secondary to spina bifida and they were excluded from study. The diagnosis was
      made in all cases by abdominal ultrasound and confirmed by excretory urography or
      (99m)technetium-dimercaptosuccinic acid scan. Voiding cystourethrography was
      performed in 40 cases (80%). Patients were followed for 2 to 11 years (mean 4.2).
      RESULTS: Associated urological anomalies were identified in 26 patients (52%)
      with horseshoe kidney, including primary vesicoureteral reflux in 13,
      ureteropelvic junction obstruction in 12 and ectopic ureter in 1. Surgical
      intervention to correct the anomalies in 15 of the 26 children (58%) involved
      pyeloplasty in 8, ureteral reimplantation in 2, endoscopic treatment for
      vesicoureteral reflux in 2, ureterolithotomy in 1, upper pole heminephrectomy in
      1 and valve fulguration in 1. No significant complications were observed in
      surgically treated patients. CONCLUSIONS: More than half of the patients with a
      clinically symptomatic horseshoe kidney have vesicoureteral reflux or
      ureteropelvic junction obstruction. Many patients with horseshoe kidney require
      surgical intervention for associated urological anomalies with good results.

PMID- 11992091
TI  - Bacteria in the chronic prostatitis-chronic pelvic pain syndrome: molecular
      approaches to critical research questions.
AB  - PURPOSE: There is a pressing need to determine the causes and consequences of,
      and optimal therapy for the chronic prostatitis-chronic pelvic pain syndrome.
      MATERIALS AND METHODS: New data suggest that bacterial infection may be critical
      in some patients. We examined the rationale for and technical approaches to
      hypothesis driven studies of bacteria in the chronic prostatitis-chronic pelvic
      pain syndrome. RESULTS: The first hypothesis was that patients with the chronic
      prostatitis-chronic pelvic pain syndrome have prostatic bacteria that distinguish
      them from controls. In pilot studies patients with inflamed expressed prostatic
      secretions were more likely to have bacterial DNAs, that is 16S ribosomal DNAs.
      Current goals are to clone, sequence and compare ribosomal DNAs from patients and
      controls to determine which bacteria are most specific to the chronic prostatitis
      chronic pelvic pain syndrome and which should be targeted in clinical trials. The
      second hypothesis was that bacterial viability correlates with the severity of
      the chronic prostatitis-chronic pelvic pain syndrome. Quantitative assays for
      bacterial elongation factor messenger RNA (tufA messenger RNA) provide tools to
      correlate bacterial viability with patient characteristics, will provide insights
      into the potential value of antimicrobial therapy and identify characteristics
      that distinguish patients most likely to respond. The third hypothesis was that
      patients with prostatic bacteria have similar bacteria in expressed prostatic
      secretions or on seminal fluid analysis and, furthermore, these bacteria differ
      from bacteria in controls. These studies would determine whether expressed
      prostatic secretions or seminal fluid analysis can be used to identify prostatic
      bacteria and may result in clinical methods for noninvasive diagnosis of
      prostatic infection. CONCLUSIONS: These studies should provide important insights
      into the causes of the chronic prostatitis-chronic pelvic pain syndrome and may
      elucidate optimal clinical evaluation and treatment in patients.

PMID- 11992092
TI  - Changes in the oxidant-antioxidant balance in the kidney of rats with
      nephrolithiasis induced by ethylene glycol.
AB  - PURPOSE: We investigated the possible mechanism of increased free radicals, the
      role of antioxidant enzymes and their correlation with renal tubular damage in
      the kidney after feeding 0.75% ethylene glycol to male Wistar rats. MATERIALS AND
      METHODS: Rats were divided into 7 experimental groups according to the duration
      of ethylene glycol feeding (1, 3, 5, 7, 9, 21 or 42 days) and into age matched
      control groups. Chemiluminescence levels were examined in blood samples (renal
      artery and vein) and in the kidney. The activities of oxidase and antioxidant
      enzymes were measured in kidney homogenates. The nitroblue tetrazolium perfusion
      method and immunohistochemical stains with ED1 and CD45 were performed. Urinary
      levels of alpha and mu-glutathione S-transferase (GST) were also measured and
      expressed in gm. urinary creatinine. RESULTS: Chemiluminescence levels of renal
      venous blood samples were elevated on days 1, 3 and 7 (p <0.05), and those of the
      kidney were elevated only on days 3 and 42 (p <0.05) compared with controls. The
      infiltration of CD45 positive cells in the kidney increased on day 7 and a
      further increase in these positive cells was noted on day 21. Fused ED1 positive
      cells surrounding the calcium oxalate crystals and adjacent to the nitroblue
      tetrazolium positive area were found on day 42. Xanthine oxidase activity showed
      no significant change, whereas nicotinamide adenine dinucleotide dependent
      oxidase activity was higher on day 5 and nicotinamide adenine dinucleotide
      phosphate dependent activity was elevated in all experimental groups (p <0.05).
      The activities of catalase and manganese superoxide dismutase were elevated in
      the early stage. On day 42 almost all antioxidant enzyme activities were
      attenuated (p <0.05) except that of catalase. The urinary levels of alpha-GST
      were elevated from day 7 until day 42, whereas levels of mu-GST were elevated
      from day 3 until day 42 except day 5. CONCLUSIONS: The possible mechanism that
      causes free radical elevation in the kidney may be different in the course of
      nephrolithiasis after ethylene glycol treatment. Initially the systemic
      circulation may bring the toxic substance into the kidney and cause it to produce
      free radicals. In the late stage gradually infiltrating leukocytes and decreased
      antioxidant enzyme activities may cause the kidney to remain under excessive
      oxidative stress.

PMID- 11992093
TI  - In vitro study of ultrasound based real-time tracking for renal stones in shock
      wave lithotripsy: Part II--a simulated animal experiment.
AB  - PURPOSE: We have previously developed and reported an ultrasound based real-time
      tracking system for renal stones. In the current study we continued to verify the
      reliability of this tracking system by a simulated animal test. MATERIALS AND
      METHODS: We used 13 prerecorded ultrasound stone trajectories to test the system.
      The real-time tracking system was implemented on the Litemed 9200
      electrohydraulic lithotriptor (LiteMed Co., Taipei, Taiwan). An artificial stone
      and tap water were sealed in a balloon. The balloon was inserted into the pelvis
      of a pig kidney. While the kidney was affixed to and moved by a simulator, it was
      immersed in a specifically designed simulated animal model tank containing tap
      water. The stone was localized by ultrasound. The kidney was moved by the
      simulator according to a prerecorded stone trajectory. A total of 3,000 shock
      waves were delivered to the stone. For each recorded stone trajectory experiments
      were done under nontracking and tracking conditions. We performed tests of the
      fragment-to-weight ratio, which denotes the performance of a shock wave
      lithotriptor when fragmenting a stone. RESULTS: The mean fragment-to-weight ratio
      was 55.3% +/- 25.9% in the nontracking and 100% +/- 0% in the tracking group. The
      difference in these 2 groups was statistically significant (paired t test p
      <0.01). CONCLUSIONS: The ultrasound based real-time tracking system proved to
      improve the performance of a shock wave lithotriptor significantly when
      fragmenting stones in a simulated animal test. We believe that the tracking
      system would greatly reduce the number of shocks and time needed for treating
      renal stones.

PMID- 11992094
TI  - Over expression of ID-1 in prostate cancer.
AB  - PURPOSE: The helix-loop-helix protein Id-1 serves to prevent basic helix-loop
      helix transcription factors from binding to DNA, thus, inhibiting the
      transcription of differentiation associated genes. Over expression of Id-1 has
      been reported in certain tumors, such as breast, esophageal, pancreatic and
      medullary thyroid cancers. In Noble rats we have previously demonstrated that up
      regulation of Id-1 is closely associated with the development of sex hormone
      induced prostate cancers. Therefore, we hypothesized that over expression of Id-1
      would also occur in human prostate cancer and Id-1 protein may serve as a
      potential marker for prostate carcinogenesis. To test this hypothesis we analyzed
      Id-1 messenger RNA and protein expression by in situ hybridization and
      immunohistochemical study in human normal prostate, benign prostatic hyperplasia
      (BPH) and prostate cancer tissues. MATERIALS AND METHODS: Pathological specimens
      were obtained from 19 patients with BPH and 47 with prostate carcinoma,
      representing a complete range of Gleason grades. A total of 12 normal prostate
      tissue specimens were used for comparison. Immunohistochemical study was
      performed using the polyclonal antibody against human Id-1 protein and an RNA
      probe was generated from Id-1 complementary DNA for in situ hybridization.
      RESULTS: Negative to weak expression of Id-1 in normal prostate or BPH tissue was
      observed on immunohistochemical study and in situ hybridization. In contrast, all
      prostate cancer biopsies showed significant positive Id-1 expression in tumor
      cells at the messenger RNA and protein levels. Furthermore, Id-1 expression was
      stronger in poorly differentiated than in well differentiated carcinomas,
      suggesting that the level of Id-1 expression may be associated with tumor
      malignancy. CONCLUSIONS: Our results suggest that over expression of Id-1 may
      have important roles in the development of prostate cancer. The potential use of
      Id-1 protein as a marker for prostate cancer should be further explored.

PMID- 11992095
TI  - Bacterial toxin N-formyl-methionyl-leucyl-phenylalanine acutely contracts human
      and rabbit detrusor through the release of eicosanoids.
AB  - PURPOSE: Uropathogenic bacteria that secrete N-formylmethionyl oligopeptides such
      as N-formyl-methionyl-leucyl-phenylalanine (f-MLP) are a common cause of urinary
      tract infections. We determined the in vitro effects of f-MLP on human and rabbit
      detrusor as well as its mechanism and site of action. MATERIALS AND METHODS:
      Reverse transcriptase-polymerase chain reaction was used to investigate
      cyclooxygenase-2 messenger RNA within the rabbit detrusor. Standard mechanical
      organ bath recording techniques were used to measure contractile activity from
      rabbit and human detrusor muscle strips. Immunohistochemistry was performed using
      macrophage specific antibodies (human BerMAC3 and rabbit RAM11) on detrusor whole
      mount specimens. RESULTS: Muscle activity recorded from human and rabbit detrusor
      showed that f-MLP caused contracture of the detrusor, which was completely
      blocked by indomethacin and partially blocked by individual cyclooxygenase-1 and
      cyclooxygenase-2 selective inhibitors. Exposure of the detrusor to exogenous
      prostaglandins indicated that f-MLP released an effective concentration of more
      than 1 microM. from an endogenous source. Immunohistochemical staining of the
      human (BerMAC3) and rabbit (RAM11) bladder demonstrated a dense network of
      resident macrophages lying within the detrusor muscle bundles, which are known to
      secrete prostaglandins during the activation of specific f-MLP receptors.
      CONCLUSIONS: Bacterial derived f-MLP contracts the detrusor through the release
      of eicosanoids from resident macrophages. These data suggest that bacterial
      activation of the resident macrophage network could participate in causing the
      symptoms of bacterial cystitis.

PMID- 11992096
TI  - High intensity focused ultrasound ablation of the vas deferens in a canine model.
AB  - PURPOSE: High intensity focused ultrasound is an ablative technology capable of
      producing thermal coagulative necrosis of sub-surface structures without injuring
      intervening tissues. We assessed the feasibility of using high intensity focused
      ultrasound to produce occlusion of the canine vas deferens. MATERIALS AND
      METHODS: A high intensity focused ultrasound transducer was incorporated into a
      hand held clip specially designed to grasp the vas deferens transcutaneously.
      Slots within the jaws of the clip ensured that the vas deferens and high
      intensity focused ultrasound target zone were properly co-located. We ablated 10
      vasa using a range of power and time parameters. At 2 weeks after ablation each
      vas, epididymis and testis was surgically harvested en bloc. Retrograde
      vasography was performed to assess vasal occlusion, followed by pathological
      analysis. RESULTS: High intensity focused ultrasound occlusion of the vas
      deferens was confirmed in 4 specimens ablated with parameters at the upper end of
      the parameter range, 2 of the 2 ablated with 7 W. for 60 seconds and 2 of the 4
      ablated with 7 W. for 30 seconds. Histological injury was noted in 8 of the 10
      ablated specimens. Skin burns that developed over 4 of the targeted vasa were
      conservatively managed. Bilateral sham procedures in a control dog resulted in
      patent vasa and no associated skin burns. CONCLUSIONS: We demonstrated the
      feasibility of noninvasive, transcutaneous high intensity focused ultrasound
      occlusion of the vas deferens with ablation powers at the upper end of the tested
      range, that is 7 W. Modifications of the hand held clip and optimization of
      ablation parameters would likely improve the success rate of this procedure.
      Refinement of this technology may provide a rapid noninvasive alternative to
      conventional vasectomy.

PMID- 11992097
TI  - The efficacy, safety and tolerability of intracavernous PNU-83757 for the
      treatment of erectile dysfunction.
AB  - PURPOSE: Despite the introduction of sildenafil citrate many men with erectile
      dysfunction remain dependent on intracavernous therapy. While the majority
      achieves satisfactory results with currently available intracavernous
      preparations, all preparations have undesirable side effects, including priapism,
      fibrosis and post-injection pain. We determined the efficacy, safety and
      tolerability of the erectogenic potassium channel opener PNU-83757. MATERIALS AND
      METHODS: We selected 66 men with erectile dysfunction of vascular etiology for
      intracavernous injection of PNU-83757 in a single dose, single blind, placebo
      controlled study. Of the 6 patients allocated into each of 11 dose groups 5
      received active drug and 1 received placebo. Groups received progressive doses of
      PNU-83757 or placebo. Holter monitoring was performed at scheduled intervals.
      Heart rate, and systolic, diastolic and mean blood pressure were assessed at
      scheduled intervals. Blood samples were obtained for pharmacokinetic study.
      Patients were evaluated at regular intervals for adverse events. Investigators
      and patients evaluated efficacy. RESULTS: The first complete erection was
      observed at 10 mcg. Of the 25 patients receiving active drug in the 60 to 140
      mcg. groups only 1 had no erectile response, 15 had partial erection and 9 had
      complete erection. No serious adverse events or cardiovascular effects were
      noted. CONCLUSIONS: The minimum effective dose for complete erection was 10 mcg.
      The erectile response reached a plateau between 60 and 140 mcg., suggesting
      minimal improvement in efficacy at higher doses. Patient evaluation of erectile
      quality corresponded well with that of investigators. PNU-83757 was efficacious
      and extremely well tolerated, and the only adverse events were mild. No
      cardiovascular side effects were observed at any dose. PNU-83757 intracavernous
      injections caused no post-injection pain in any patient, which may make PNU-83757
      superior to alprostadil in a select group. Further study is required to evaluate
      the efficacy of PNU-83757 combined with other drugs and with sexual stimulation.

PMID- 11992098
TI  - The effects of melatonin on ischemia-reperfusion induced changes in rat corpus
      cavernosum.
AB  - PURPOSES: We determined the change in contractile activity and oxidant damage
      after ischemia-reperfusion of rat corpus cavernosum and investigated the effects
      of melatonin (Sigma Chemical Co., St. Louis, Missouri) on these parameters.
      MATERIALS AND METHODS: The abdominal aorta of male Wistar albino rats was
      occluded to induce ischemia-reperfusion. Melatonin (10 mg./kg.) or vehicle (1%
      alcohol in saline per kg.) was administered subcutaneously before ischemia
      reperfusion. In the sham operated control group the abdominal aorta was left
      intact and the rats were treated with melatonin or vehicle. After decapitation
      corporeal tissues were placed in organ baths or stored for biochemical
      measurements. RESULTS: In sham operated rats phenylephrine added cumulatively
      caused a concentration dependent contraction in corpus cavernosum strips
      precontracted with KCl and acetylcholine added cumulatively to strips
      precontracted with phenylephrine caused a dose dependent relaxation response. In
      the ischemia-reperfusion group contraction and relaxation responses decreased
      significantly compared within controls. Melatonin treatment in the ischemia
      reperfusion group reversed these responses. Myeloperoxidase activity and the
      lipid peroxidation level of the corporeal tissues in the ischemia-reperfusion
      group were significantly higher than in the sham operated control group.
      Melatonin treatment in the ischemia-reperfusion group decreased myeloperoxidase
      activity and the lipid peroxidation level compared with ischemia-reperfusion
      alone, whereas melatonin treatment alone had no significant effect on these
      parameters. CONCLUSIONS: In this study the corporeal tissues of rats exposed to
      ischemia-reperfusion had lower responses to contractile and relaxant agents than
      those of sham operated rats. Treatment with melatonin before ischemia-reperfusion
      almost completely reversed smooth muscle responses and prevented the increased
      myeloperoxidase activity and lipid peroxidation of corporeal tissues.

PMID- 11992099
TI  - Potassium channels and human corporeal smooth muscle cell tone: further evidence
      of the physiological relevance of the Maxi-K channel subtype to the regulation of
      human corporeal smooth muscle tone in vitro.
AB  - PURPOSE: Recent evidence indicates that the large conductance, voltage dependent,
      Ca2+ sensitive K channel or Maxi-K has an important role in the modulation of
      human corporeal smooth muscle tone and, thus, in erectile capacity. We further
      clarified the contribution of the Maxi-K channel subtype to the generation of
      contractile responses in isolated human corporeal tissue strips. MATERIALS AND
      METHODS: We performed pharmacological studies of phenylephrine contracted
      isolated corporeal tissue strips in the presence and absence of the 2 Maxi-K
      channel blockers tetraethylammonium chloride (TEA) and charybdotoxin, and the
      Maxi-K opener NS1619. K channel treatment effects were evaluated using 2
      parameters, including 1) the steady state parameter of the empirically determined
      peak magnitude of the steady state contractile response and 2) the kinetic
      parameter of time required to achieve half of the peak steady state contractile
      response or half-time. Electrophysiological studies in freshly isolated and
      cultured myocytes were performed in parallel to corroborate findings further at
      the tissue level. RESULTS: Pre-incubating isolated human corporeal tissue strips
      with 1 mM. TEA and 1 microM. charybdotoxin was associated with an approximate 20%
      increase in the peak steady state contractile response and a corresponding
      approximate 20% decrease in the half-time of the phenylephrine induced
      contractile response. Conversely, pre-incubation with 10 microM. NS1619 produced
      a significant, approximately 20% decrease in the peak steady state contractile
      response and an approximate 38% increase in the half-time of the phenylephrine
      induced contractile response. Adding 30 to 180 microM. NS1619 to phenylephrine
      pre-contracted smooth muscle strips resulted in a 30% to 50% reduction in steady
      state contractile tension. No detectable effect of NS1619 was observed in 120 mM.
      KCl or 100 mM. TEA pre-contracted corporeal tissue strips. Whole cell recordings
      of freshly isolated and cultured corporeal myocytes confirmed that 30 microM.
      NS1619 induced a charybdotoxin sensitive hyperpolarizing current mediated by the
      Maxi-K channel. CONCLUSIONS: These in vitro studies confirm and extend previous
      observations indicating the importance of the Maxi-K channel for regulating human
      corporeal smooth muscle tone, and by extension, erectile capacity and function.

PMID- 11992100
TI  - Enhanced force generation by corpus cavernosum smooth muscle in rabbits with
      partial bladder outlet obstruction.
AB  - PURPOSE: Growing clinical evidence suggests that benign prostatic hyperplasia
      induced partial bladder outlet obstruction is associated with an increased
      incidence of erectile dysfunction. We determined whether corpus cavernosum smooth
      muscle from rabbits with partial bladder outlet obstruction show any molecular or
      functional differences versus controls. MATERIALS AND METHODS: Force generation
      and relaxation of corpus cavernosum smooth muscle 2 weeks after partial bladder
      outlet obstruction by 125 mM. KCl, phenylephrine and field stimulation were
      determined. Expression of total smooth muscle myosin and alternatively spliced
      smooth muscle myosin isoforms were determined by reverse transcriptase-polymerase
      chain reaction (RT-PCR), quantitative competitive RT-PCR, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blot analysis. Corpus cavernosum
      smooth muscle from sections of the penis were analyzed morphologically by
      immunofluorescence microscopy using antibodies to smooth muscle myosin and
      neurofilament protein. RESULTS: Corpus cavernosum smooth muscle from rabbits with
      partial bladder outlet obstruction generated 40% to 50% more force than that of
      sham operated rabbits in response to KCl or phenylephrine and was more difficult
      to relax. Although quantitative competitive RT-PCR and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed that corpus cavernosum smooth muscle
      from rabbits with partial bladder outlet obstruction expressed only slightly more
      total smooth muscle myosin at the messenger RNA and protein levels, expression of
      the high adenosine triphosphatase isoform SM-B increased 2-fold. Morphological
      examination of corpus cavernosum smooth muscle sections revealed decreased
      innervation and increased smooth muscle bundle size. CONCLUSIONS: We present the
      novel finding of molecular and functional changes in the corpus cavernosum smooth
      muscle associated with partial bladder outlet obstruction. Although the inclusion
      of sham operation ruled out direct injury during surgery, a change in corpus
      cavernosum smooth muscle innervation induced by nerve compression by the ligature
      is likely to induce trophic changes in the corpus cavernosum smooth muscle
      leading to over expression of the SM-B smooth muscle myosin isoform, increased
      contractility and impaired relaxation.

PMID- 11992112
TI  - ROCK and Dia have opposing effects on adherens junctions downstream of Rho.
AB  - Adherens junctions (AJs) are crucial for maintaining the integrity of epithelial
      tissues and are often disrupted during tumour progression. Rho family proteins
      have been shown to regulate adherens junctions. We find that activation of the
      effector kinase ROCK and acto-myosin contraction disrupts AJs downstream of Rho.
      In contrast, signalling through the Rho effector Dia1 is required to ensure a
      dynamically stable interface between cells and the maintenance of adherens
      junction complexes. The ability of Dia1 to regulate the actin network is crucial
      for the localization of adherens junction components to the cell periphery.

PMID- 11992113
TI  - A computational role for slow conductances: single-neuron models that measure
      duration.
AB  - Humans effortlessly interpret speech and music, whose patterns can contain sound
      durations up to thousands of milliseconds. How nervous systems measure such long
      durations is unclear. We show here that model neurons containing physiological
      slow conductances are 'naturally' sensitive to duration, replicate known duration
      sensitive neurons and can be 'tuned' to respond to a wide range of specific
      durations. In addition, these models reproduce several other properties of
      duration-sensitive neurons not selected for in model construction. These data,
      and the widespread presence of slow conductances in nervous systems, suggest that
      slow conductances might play a major role in duration measurement.

PMID- 11992114
TI  - Sniffing neuropeptides: a transnasal approach to the human brain.

PMID- 11992115
TI  - Stable perception of visually ambiguous patterns.
AB  - During the viewing of certain patterns, widely known as ambiguous or puzzle
      figures, perception lapses into a sequence of spontaneous alternations, switching
      every few seconds between two or more visual interpretations of the stimulus.
      Although their nature and origin remain topics of debate, these stochastic
      switches are generally thought to be the automatic and inevitable consequence of
      viewing a pattern without a unique solution. We report here that in humans such
      perceptual alternations can be slowed, and even brought to a standstill, if the
      visual stimulus is periodically removed from view. We also show, with a visual
      illusion, that this stabilizing effect hinges on perceptual disappearance rather
      than on actual removal of the stimulus. These findings indicate that
      uninterrupted subjective perception of an ambiguous pattern is required for the
      initiation of the brain-state changes underlying multistable vision.

PMID- 11992116
TI  - Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor
      1.
AB  - The vanilloid receptor-1 (VR1) is a heat-gated ion channel that is responsible
      for the burning sensation elicited by capsaicin. A similar sensation is reported
      by patients with esophagitis when they consume alcoholic beverages or are
      administered alcohol by injection as a medical treatment. We report here that
      ethanol activates primary sensory neurons, resulting in neuropeptide release or
      plasma extravasation in the esophagus, spinal cord or skin. Sensory neurons from
      trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells
      responded to ethanol in a concentration-dependent and capsazepine-sensitive
      fashion. Ethanol potentiated the response of VR1 to capsaicin, protons and heat
      and lowered the threshold for heat activation of VR1 from approximately 42
      degrees C to approximately 34 degrees C. This provides a likely mechanistic
      explanation for the ethanol-induced sensory responses that occur at body
      temperature and for the sensitivity of inflamed tissues to ethanol, such as might
      be found in esophagitis, neuralgia or wounds.

PMID- 11992117
TI  - A rapid switch in sympathetic neurotransmitter release properties mediated by the
      p75 receptor.
AB  - Cardiac function is modulated by norepinephrine release from innervating
      sympathetic neurons. These neurons also form excitatory connections onto cardiac
      myocytes in culture. Here we report that brain-derived neurotrophic factor (BDNF)
      altered the neurotransmitter release properties of these sympathetic neuron
      myocyte connections in rodent cell culture, leading to a rapid shift from
      excitatory to inhibitory cholinergic transmission in response to neuronal
      stimulation. Fifteen minutes of BDNF perfusion was sufficient to cause this shift
      to inhibitory transmission, indicating that BDNF promotes preferential release of
      acetylcholine in response to neuronal stimulation. We found that p75(-/-) neurons
      did not release acetylcholine in response to BDNF and that neurons overexpressing
      p75 showed increased cholinergic transmission, indicating that the actions of
      BDNF are mediated through the p75 neurotrophin receptor. Our findings indicate
      that p75 is involved in modulating the release of distinct neurotransmitter
      pools, resulting in a functional switch between excitatory and inhibitory
      neurotransmission in individual neurons.

PMID- 11992118
TI  - Na(x) channel involved in CNS sodium-level sensing.

PMID- 11992119
TI  - Ion channel properties underlying axonal action potential initiation in pyramidal
      neurons.
AB  - A high density of Na+ channels in the axon hillock, or initial segment, is
      believed to determine the threshold for action potential initiation in neurons.
      Here we report evidence for an alternative mechanism that lowers the threshold in
      the axon. We investigated properties and distributions of ion channels in outside
      out patches from axons and somata of layer 5 pyramidal neurons in rat neocortical
      slices. Na+ channels in axonal patches (<30 microm from the soma) were activated
      by 7 mV less depolarization than were somatic Na+ channels. A-type K+ channels,
      which were prominent in somatic and dendritic patches, were rarely seen in axonal
      patches. We incorporated these findings into numerical simulations which indicate
      that biophysical properties of axonal channels, rather than a high density of
      channels in the initial segment, are most likely to determine the lowest
      threshold for action potential initiation.

PMID- 11992120
TI  - nagie oko, encoding a MAGUK-family protein, is essential for cellular patterning
      of the retina.
AB  - A layered organization of cells is a common architectural feature of many
      neuronal formations. Mutations of the zebrafish gene nagie oko (nok) produce a
      severe disruption of retinal architecture, indicating a key role for this locus
      in neuronal patterning. We show that nok encodes a membrane-associated guanylate
      kinase-family scaffolding protein. Nok localizes to the vicinity of junctional
      complexes in retinal neuroepithelium and in the photoreceptor cell layer. Mosaic
      analysis indicates that the nok retinal patterning phenotype is not cell
      autonomous. We propose that nok function in patterning of postmitotic neurons is
      mediated through neuroepithelial cells and is necessary for guiding neurons to
      their proper destinations in retinal laminae.

PMID- 11992121
TI  - Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.
AB  - Although many genes that predispose for epilepsy in humans have been determined,
      those that underlie the classical syndromes of idiopathic generalized epilepsy
      (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1,
      encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A
      (GABA(A)), is found in affected individuals of a large French Canadian family
      with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A)
      receptors that contain the mutant subunit show a lesser amplitude of GABA
      activated currents in vitro, indicating that seizures may result from loss of
      function of this inhibitory ligand-gated channel. Our results confirm that
      mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy
      syndrome in humans.

PMID- 11992122
TI  - Clustering of housekeeping genes provides a unified model of gene order in the
      human genome.
AB  - It is often supposed that, except for tandem duplicates, genes are randomly
      distributed throughout the human genome. However, recent analyses suggest that
      when all the genes expressed in a given tissue (notably placenta and skeletal
      muscle) are examined, these genes do not map to random locations but instead
      resolve to clusters. We have asked three questions: (i) is this clustering true
      for most tissues, or are these the exceptions; (ii) is any clustering simply the
      result of the expression of tandem duplicates and (iii) how, if at all, does this
      relate to the observed clustering of genes with high expression rates? We provide
      a unified model of gene clustering that explains the previous observations. We
      examined Serial Analysis of Gene Expression (SAGE) data for 14 tissues and found
      significant clustering, in each tissue, that persists even after the removal of
      tandem duplicates. We confirmed clustering by analysis of independent expressed
      sequence tag (EST) data. We then tested the possibility that the human genome is
      organized into subregions, each specializing in genes needed in a given tissue.
      By comparing genes expressed in different tissues, we show that this is not the
      case: those genes that seem to be tissue-specific in their expression do not, as
      a rule, cluster. We report that genes that are expressed in most tissues
      (housekeeping genes) show strong clustering. In addition, we show that the
      apparent clustering of genes with high expression rates is a consequence of the
      clustering of housekeeping genes.

PMID- 11992123
TI  - Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced
      S-phase entry.
AB  - Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer.
      In the absence of other genetic alterations, this deregulation results in lack of
      differentiation, hyperproliferation and apoptosis. The pRB protein acts as a
      transcriptional repressor by targeting the E2F transcription factors, whose
      functions are required for entry into S phase. Increased E2F activity can induce
      S phase in quiescent cells--this is a central element of most models for the
      development of cancer. We show that although E2F1 alone is not sufficient to
      induce S phase in diploid mouse and human fibroblasts, increased E2F1 activity
      can result in S-phase entry in diploid fibroblasts in which the p53-mediated G1
      checkpoint is suppressed. In addition, we show that E2F1 can induce S phase in
      primary mouse fibroblasts lacking pRB. These results indicate that, in addition
      to acting as an E2F-dependent transcriptional repressor, pRB is also required for
      the cells to retain the G1 checkpoint in response to unprogrammed proliferative
      signals.

PMID- 11992124
TI  - A genomic screen for genes upregulated by demethylation and histone deacetylase
      inhibition in human colorectal cancer.
AB  - Aberrant hypermethylation of gene promoters is a major mechanism associated with
      inactivation of tumor-suppressor genes in cancer. We previously showed this
      transcriptional silencing to be mediated by both methylation and histone
      deacetylase activity, with methylation being dominant. Here, we have used cDNA
      microarray analysis to screen for genes that are epigenetically silenced in human
      colorectal cancer. By screening over 10,000 genes, we show that our approach can
      identify a substantial number of genes with promoter hypermethylation in a given
      cancer; these are distinct from genes with unmethylated promoters, for which
      increased expression is produced by histone deacetylase inhibition alone. Many of
      the hypermethylated genes we identified have high potential for roles in
      tumorigenesis by virtue of their predicted function and chromosome position. We
      also identified a group of genes that are preferentially hypermethylated in
      colorectal cancer and gastric cancer. One of these genes, SFRP1, belongs to a
      gene family; we show that hypermethylation of four genes in this family occurs
      very frequently in colorectal cancer, providing for (i) a unique potential
      mechanism for loss of tumor-suppressor gene function and (ii) construction of a
      molecular marker panel that could detect virtually all colorectal cancer.

PMID- 11992125
TI  - Metal binding and base ionization in the U6 RNA intramolecular stem-loop
      structure.
AB  - U6 RNA is a key component of the catalytic core of the spliceosome. A metal ion
      essential for the first catalytic step of pre-mRNA splicing binds to the U80 Sp
      phosphate oxygen within the yeast U6 intramolecular stem-loop (ISL). Here we
      present the first structural data for U6 RNA, revealing the three-dimensional
      structure of the highly conserved U6 ISL. The ISL binds metal ion at the U80 site
      with the same stereo specificity as the intact spliceosome. The metal-binding
      site is adjacent to a readily protonated C.A wobble pair. Protonation of the C.A
      pair and metal binding are mutually antagonistic. These results support a
      ribozyme model for U6 RNA function and suggest a possible mechanism for the
      regulation of RNA splicing.

PMID- 11992126
TI  - E. coli aconitase B structure reveals a HEAT-like domain with implications for
      protein-protein recognition.
AB  - The major bifunctional aconitase of Escherichia coli (AcnB) serves as either an
      enzymic catalyst or a mRNA-binding post-transcriptional regulator, depending on
      the status of its iron sulfur cluster. AcnB represents a large, distinct group of
      Gram-negative bacterial aconitases that have an altered domain organization
      relative to mitochondrial aconitase and other aconitases. Here the 2.4 A
      structure of E. coli AcnB reveals a high degree of conservation at the active
      site despite its domain reorganization. It also reveals that the additional
      domain, characteristic of the AcnB subfamily, is a HEAT-like domain, implying a
      role in protein protein recognition. This domain packs against the remainder of
      the protein to form a tunnel leading to the aconitase active site, potentially
      for substrate channeling.

PMID- 11992127
TI  - The SAM domain of polyhomeotic forms a helical polymer.
AB  - The polycomb group (PcG) proteins are important in the maintenance of stable
      repression patterns during development. Several PcG members contain a protein
      protein interaction module called a SAM domain (also known as SPM, PNT and HLH).
      Here we report the high-resolution structure of the SAM domain of polyhomeotic
      (Ph). Ph-SAM forms a helical polymer structure, providing a likely mechanism for
      the extension of PcG complexes. The structure of the polymer resembles that
      formed by the SAM domain of another transcriptional repressor, TEL. The formation
      of these polymer structures by SAM domains in two divergent repressors suggests a
      conserved mode of repression involving a higher order chromatin structure.

PMID- 11992128
TI  - The Canadian Cardiovascular Society and YOU!

PMID- 11992129
TI  - Life in the hot seat.

PMID- 11992130
TI  - The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years
      later.
AB  - BACKGROUND: The Canadian Cardiovascular Society (CCS) grading of angina pectoris
      was described in the medical literature in 1976. OBJECTIVES: To describe the
      origin of this grading, its worldwide acceptance, critiques, perceived
      limitations and alternative systems. METHODS: The present author, who chaired the
      CCS ad hoc committee that developed this grading system in 1972, used
      documentation based on personal correspondence, and information from medline and
      international citation indexes searches. RESULTS: The CCS committee's mandate was
      to standardize the definition of terms used in reporting studies of coronary
      artery disease and coronary artery bypass graft surgery. The committee defined a
      four-level system modelled on the New York Heart Association functional
      classification of patients with diseases of the heart, and the American Medical
      Association classes of organic heart diseases. Threshold activities that produced
      angina were detailed to assess reliably the severity of exertional angina by
      independent observers, and changes over time. The grading system has been cited
      over 650 times in the literature since its official publication in 1976. Although
      this grading system was found to be generally relevant and practical, several
      imperfections and potential limitations were reported, the most pertinent being
      the criterion "anginal syndrome may be present at rest" included in grade IV,
      which was found to be inappropriate and confusing. The prognostic significance of
      the grading system, despite the finding that this was not its primary goal, was
      also thought to be inadequate. CONCLUSION: Although this grading system of the
      severity of effort angina has been accepted throughout the world over the past 30
      years, a revision is desirable considering its potential imperfections and
      inconsistencies with present day management of ischemic heart disease.

PMID- 11992131
TI  - Biventricular pacing improves quality of life and exercise tolerance in patients
      with heart failure and intraventricular conduction delay.
AB  - BACKGROUND: Biventricular pacing improves left ventricular dysynchrony, leading
      to improvement in congestive heart failure symptoms. The extent of placebo
      effect, the predictors of response and the long term benefits are unknown.
      PATIENTS AND METHODS: Forty-five patients with symptomatic congestive heart
      failure underwent implantation of a biventricular pacing system over a 30-month
      period (age 65 10 years, 37 men). Patients underwent implantation of a
      biventricular pacemaker or implantable defibrillator one month or longer after
      stabilization of congestive heart failure on maximal medical therapy, including
      angiotensin-converting enzyme inhibitors in 84% of patients and beta-blockers in
      56% of patients. Three patients had New York Heart Association (NYHA) class II
      heart failure, 34 had NYHA class III and eight had NYHA class IV. Cardiomyopathy
      was ischemic in 31 patients, dilated in 12 and the result of other causes in two.
      The left ventricular ejection fraction was 19 5%. RESULTS: Implantation of the
      biventricular pacing system was successful in 38 of 45 patients (84%). Two
      patients had successful implantation with a second attempt, and one patient had
      an epicardial lead implant. Lead dislodgement occurred in four patients, with
      successful repositioning in all. During a mean follow-up of 10 7 months, the
      Minnesota Living with Heart Failure Questionnaire quality of life index score
      improved from 62 16 to 42 22 at one month (P<0.001), but subsequently returned to
      intermediate levels (55 26 at three months, 48 26 at six months and 56 34 at one
      year, P=0.50). In seven patients with deferred device activation, quality of life
      scores also improved by 10 15 points from baseline to one month with VDI 35
      pacing, and improved a further 15 20 points with left ventricular lead
      activation. The mean NYHA class fell from 3.1 0.5 at baseline to 2.7 0.7 at one
      month (P=0.006) and remained stable thereafter (2.8 0.9 at three months, 2.8 0.9
      at six months). Six patients died during follow-up, one patient had a cardiac
      transplantation and subsequently died, one patient had a successful cardiac
      transplantation and one patient underwent insertion of a left ventricular assist
      device. Death occurred due to progressive heart failure in five patients, sudden
      death occurred in one patient and a noncardiovascular cause resulted in the death
      of one patient. An analysis of NYHA responders (NYHA class improvement of 1 or
      more at last follow-up, 44% of patients) and quality of life responders (score
      improvement of 10 or more at last follow-up, 57% patients) did not show any
      difference in age, sex, heart failure etiology, QRS width, ejection fraction or
      baseline NYHA class. CONCLUSIONS: Biventricular pacing improves quality of life
      and NYHA class in patients with advanced heart failure and intraventricular
      conduction delay. The attenuated benefit seen over time may be related to initial
      placebo effect or simple dual- chamber pacing, or the natural history of the
      underlying disease. Identification of patients most likely to respond to
      biventricular pacing was not possible.

PMID- 11992132
TI  - Effects of the angiotensin receptor antagonist losartan on the response of the
      left main coronary artery to cold pressor test in patients with essential
      hypertension as assessed by echocardiography.
AB  - BACKGROUND: Angiotensin II can impair endothelial function, which is mediated by
      the angiotensin II type 1 receptor subtype. OBJECTIVE: To test the hypothesis
      that treatment with the angiotensin II type 1 receptor antagonist losartan would
      restore the normal dilation of the left main coronary artery to the cold pressor
      test in patients with essential hypertension, as assessed by echocardiography.
      PATIENTS AND METHODS: The study population included 24 patients with mild to
      moderate essential hypertension and 24 matched, healthy subjects. The cold
      pressor test-induced and nitroglycerin-induced changes in the left main coronary
      artery diameter were measured by echocardiography at the end of the washout
      period and after 12 weeks of losartan administration. RESULTS: The percentage
      change in the left main coronary artery diameter induced by the cold pressor test
      in patients with hypertension (-4.3 8.7%) was significantly lower than that in
      control subjects (10.5 3.9%, P<0.0001). The percentage change in the left main
      coronary artery diameter induced by the cold pressor test in patients with
      essential hypertension after losartan treatment (13.7 8.0%) was significantly
      higher than that before losartan treatment (-4.3 8.7%, P<0.0001). The percentage
      change in the left main coronary artery diameter induced by the cold pressor test
      after losartan treatment was not significantly different between the 14 patients
      with hypertension who had satisfactory control of blood pressure (14.1 8.8%) and
      the 10 patients with hypertension who did not have satisfactory control of blood
      pressure (13.1 7.0, P=0.8). Losartan treatment in patients with essential
      hypertension did not modify the percentage change in the left main coronary
      artery diameter caused by sublingual administration of nitroglycerin (23.2 14.4%
      versus 27.2 13.5, P=0.2). CONCLUSIONS: The present study demonstrates that
      treatment with the angiotensin II type 1 receptor antagonist losartan normalized
      the response of the left main coronary artery to the cold pressor test in
      patients with mild to moderate essential hypertension, and that this effect is
      not dependent on the reduction of blood pressure.

PMID- 11992133
TI  - Preoperative cardiovascular risk factor control in elective coronary artery
      bypass graft patients: a failure of present management.
AB  - BACKGROUND: After coronary artery bypass graft (CABG) patients are at high risk
      for disease progression and future cardiac events. Risk factor control can reduce
      subsequent clinical events and mortality. The appropriateness of cardiovascular
      risk factor management in CABG patients is largely unknown. OBJECTIVES: To
      evaluate the presence of cardiovascular risk factors, their treatment and the
      adequacy of that treatment in patients just before elective CABG PATIENTS AND
      METHODS: Over a six-month period in 1999, 120 patients who underwent elective
      CABG at a single centre were assessed. All patients were assessed for the
      presence of important, known, modifiable cardiovascular risk factors (smoking,
      hypertension, hypercholesterolemia, obesity and diabetes), and the adequacy of
      the control of these risk factors, as determined by published consensus
      conference guidelines. RESULTS: Ninety-five per cent of patients were receiving
      treatment for their risk factors. Twenty of 86 patients had their hyperlipidemia
      controlled, only 10 of 36 patients with diabetes had their glucose well
      controlled, 56 of 82 patients had adequate control of their hypertension, 21 of
      120 patients were current smokers, 78 of 120 patients were obese and only 13 of
      120 patients had all risk factors under control. CONCLUSIONS: As expected, the
      prevalence of all the risk factors was very high. Despite a high level of medical
      treatment, risk factor management was very poor. More effort needs to go into
      active, long term management, and patient education and motivation, if any
      substantial progress is to be made in reducing future cardiac events in patients
      after CABG.

PMID- 11992134
TI  - Opening Pandora's box: parental anxiety and the assessment of childhood murmurs.
AB  - BACKGROUND: Most family physicians and pediatricians recognize the induction of
      parental anxiety when a newly diagnosed childhood murmur is discussed with a
      child's parent. OBJECTIVES: To assess parental anxiety before and after
      consultation with a pediatric cardiologist for assessment of a childhood murmur.
      The study investigated the relationship between anxiety and parental
      understanding of murmurs, and assessed the possible role of the primary
      physician's initial diagnosis of the child's murmur on the anxiety level of
      parents. SUBJECTS AND METHODS: One hundred ninety-five consecutive parents who
      presented with their child to the Alberta Children's Hospital Cardiology Clinic,
      Calgary, Alberta, were recruited. The children were referred for an initial
      consultation with a pediatric cardiologist for assessment of a heart murmur noted
      previously by the referring physicians. Before consultation, the patients were
      divided into three murmur groups for diagnosis: innocent, pathological and
      unknown. Anxiety questionnaires, as well as questionnaires assessing basic parent
      understanding of childhood murmurs, were administered to one of the parents pre-
      and postconsultation. RESULTS: The initial diagnosis given to the caregiver by
      the primary care physician as the reason for referral did not seem to affect the
      level of parental anxiety within groups. As expected, postconsultation anxiety
      levels were significantly higher in parents whose children received a
      pathological diagnosis from the pediatric cardiologist. A significant drop in
      parental anxiety post-consultation was seen in all parent groups, including
      parents of a child diagnosed with a significant cardiac problem or pathology
      requiring further investigation and/or cardiac follow-up. There was a consistent
      correlation between higher scores on parental understanding and lower levels of
      parental anxiety. CONCLUSION: The present study confirms that the finding of a
      childhood murmur by the family doctor or pediatrician induces significant
      parental anxiety, even when the presumptive diagnosis is that of an 'innocent'
      murmur. Pediatric cardiology consultation decreases parental anxiety, even in
      parents whose child has been given a diagnosis of pathology. The correlation
      between poor understanding of murmurs and high parental anxiety suggests that
      further study is required on the role of the referring physician in augmenting
      parental understanding of the term 'heart murmur' and the referral process.

PMID- 11992135
TI  - Cardioprotective effects of vasopeptidase inhibitors.
AB  - In all cardiovascular disease, there is an imbalance between vasoconstrictor and
      vasodilator systems that favours vasoconstriction. Angiotensin-converting enzyme
      (ACE) inhibitors help to redress this imbalance. ACE inhibitors reduce
      angiotensin II and, by blocking the metabolism of bradykinin, ACE inhibitors
      upregulate nitric oxide and prostacycline. Neutral endopeptidase (NEP) is the
      major enzymatic pathway for the degradation of natriuretic peptides and
      adrenomedullin, and is a secondary enzymatic pathway for the degradation of
      kinins. Thus, inhibition of NEP increases levels of natriuretic and vasodilatory
      peptides. Vasopeptidase inhibitors (VPIs), by simultaneously inhibiting ACE and
      NEP, reduce vasocontriction and enhance vasodilation; thus, they improve local
      blood flow, and improve sodium and water excretion. In addition, they likely
      reduce growth, fibrosis, coagulability, adhesive molecule expression and monocyte
      adhesion, and inflammation in the vasculature and the heart. In clinical studies,
      they have proven to be very effective in treating hypertension. The major side
      effect of the drugs appears to be angioedema. Thus, VPIs are promising new drugs
      for the treatment of cardiovascular diseases.

PMID- 11992136
TI  - The 'wet Westermark' sign.
AB  - A 67-year-old woman experienced dyspnea and exertional intolerance after
      aortocoronary bypass grafting. Early in the postoperative course, she had mild
      heart failure due to volume overload. Regional oligemia was appreciated on the
      chest radiograph. The oligemia led to the consideration of pulmonary embolism and
      was corroborated by perfusion scanning, which demonstrated defects in the same
      areas. Interstitial markings, accentuated by the heart failure, served as a
      serendipitous form of radiographic 'contrast' - a marker of blood perfusion and,
      in the present case, regional underperfusion. Therefore, mild heart failure
      accentuates 'Westermark's' sign.

PMID- 11992137
TI  - Audible implantable cardioverter defibrillator alarms detect intermittent
      conductor discontinuity.
AB  - The lead conductor integrity of implantable cardioverter defibrillator devices is
      inferred from impedance measurements; however, intermittent discontinuity can be
      difficult to detect or confirm. Newer devices can perform daily lead impedance
      self-testing, and some even have audible alarms that promptly warn patients of
      anomalies. In the present case, the audible alarms were solely responsible for
      the timely identification of an intermittent, otherwise clinically
      nonreproducible, form of potentially fatal implantable cardioverter defibrillator
      system failure.

PMID- 11992138
TI  - Right heart obstruction from a balloon-like sinus of Valsalva aneurysm in a
      patient with Down syndrome.
AB  - A 40-year-old man with Down syndrome presented with right heart failure. He was
      markedly obese and had severe developmental delay. There was marked edema and an
      early diastolic sound. Transthoracic echocardiography suggested a right heart
      mass. Transesophageal echocardiography revealed an unruptured balloon-like sinus
      of Valsalva aneurysm within the right atrium that obstructed the tricuspid
      orifice. The patient died in hospital of mixed obstructive and/or septic shock.

PMID- 11992139
TI  - Chronic aortic dissection: 27 years after aortic valve replacement.

PMID- 11992140
TI  - The angina grading system of the Canadian Cardiovascular Society.

PMID- 11992141
TI  - A critical review on Chagas disease chemotherapy.
AB  - In this "Critical Review" we made a historical introduction of drugs assayed
      against Chagas disease beginning in 1912 with the works of Mayer and Rocha Lima
      up to the experimental use of nitrofurazone. In the beginning of the 70s,
      nifurtimox and benznidazole were introduced for clinical treatment, but results
      showed a great variability and there is still a controversy about their use for
      chronic cases. After the introduction of these nitroheterocycles only a few
      compounds were assayed in chagasic patients. The great advances in vector control
      in the South Cone countries, and the demonstration of parasite in chronic
      patients indicated the urgency to discuss the etiologic treatment during this
      phase, reinforcing the need to find drugs with more efficacy and less toxicity.
      We also review potential targets in the parasite and present a survey about new
      classes of synthetic and natural compounds studied after 1992/1993, with which we
      intend to give to the reader a general view about experimental studies in the
      area of the chemotherapy of Chagas disease, complementing the previous papers of
      Brener (1979) and De Castro (1993).

PMID- 11992142
TI  - Presence of triatominae (Hemiptera, Reduviidae) and risk of transmission of
      Chagas disease in Colima, Mexico.
AB  - With the purpose of evaluating the risk of transmission of the Chagas disease in
      the State of Colima, Mexico, an entomological survey was performed to obtain
      triatominae and the rate of infection by Trypanosoma cruzi determined by
      examination of its dejections. Two hundred eighteen houses located in 16 villages
      were sampled. In each house the intradomestic and peridomestic habitats were
      examined by the man-hour-house method, sensor boxes and mouse-baited traps. Also,
      12 silvatic places were explored around the same areas using the same techniques
      as the ones sampled. In total, 456 specimens were captured, of which 139
      correspond to Triatoma phyllosoma pallidipennis; 80 to T.p. longipennis; one
      specimen of T. dimidiata and 236 nymphs of Triatoma sp. Two hundred ninety seven
      insects were captured in the intradomestic habitat, 132 in the peridomestic and
      26 in the silvatic. The index of positive houses was 27%, located in the central
      area of the state. The rate of natural infection with T. cruzi showed 25.6%. This
      results confirmed the presence of two important vectors of the Chagas disease in
      Colima. Its preference for the domestic habitat and its high levels of natural
      infection with T. cruzi suggested the existence of a significant risk for its
      transmission in this area of the country.

PMID- 11992143
TI  - Epidemiological and serological aspects in canine toxoplasmosis in animals with
      nervous symptoms.
AB  - The presence of anti-Toxoplasma gondii IgM and IgG antibodies was studied in
      samples of blood serum taken from eighty dogs with nervous symptoms at the
      Servico de Enfermidades Infecciosas dos Animais, Faculdade de Medicina
      Veterinaria e Zootecnia, Unesp, Botucatu, Sao Paulo, Brazil. The frequency of IgG
      titers were 16 (13.7%), 64 (13.7%), and 256 (5%), and for IgM titers were 16
      (7.5%), 64 (15%), and 256 (8.7%). Positive reactions were more frequent in the
      older animals, males, from a rural environment, in constant contact with small
      animals, principally birds and rodents. There was a higher frequency of a
      positive reaction in dogs fed with kitchen food, especially in those fed with raw
      ingredients. The most common neurological pictures were alterations in
      consciousness, in movement, and in the hand-cart test. The percentage of reagents
      with specific IgM antibodies was high, indicating active infections, but the
      possibility of co-infection with the distemper virus can not be discarded, and
      this may be a predisposing factor for toxoplasmosis infection, once the distemper
      virus has a potent immunosuppressive action.

PMID- 11992144
TI  - Cattle dung breeding Diptera in pastures in southeastern Brazil: diversity,
      abundance and seasonallity.
AB  - Diptera that breed in undisturbed cattle droppings in pastures present great
      diversity and abundance, and several species are of veterinary importance and may
      cause economic losses. To survey the diversity, abundance and seasonality of
      Diptera associated to this microhabitat, 83 samples of 10 dung pats each were
      taken from April 1992 to April 1994 in the vicinity of Sao Carlos, State of Sao
      Paulo, Southeastern Brazil. A total of 46,135 Diptera belonging to 20 families
      and at least 51 species were found to breed in the pats. The most abundant and
      diverse families were Sepsidae, Muscidae, Sarcophagidae and Sphaeroceridae. In
      general, the abundance was higher from October to March, the warm and wet months.
      The importance of some Diptera, both as horn fly enemies and as cattle dung
      decaying agents, is discussed.

PMID- 11992145
TI  - Triatomines involved in domestic and wild Trypanosoma cruzi transmission in
      Concepcion, Corrientes, Argentina.
AB  - An entomological and serological survey was performed in three localities of the
      Department of Concepcion, Province of Corrientes, Argentina in 1998 and 1999, to
      identify triatomines species involved in domestic and wild transmission of Chagas
      disease. Triatomines were collected by man/hour capture in 32 houses randomly
      selected and 44 nearby outdoor ecotopes. Trypanosoma cruzi infection in
      triatomines was assessed by direct microscopic observation (400x) of feces and
      polymerase chain reaction. Serological techniques used for people were Indirect
      Hemagglutination Test and Indirect Fluorescent Test. Triatomines were collected
      in 28.1% of the houses and 31.8% of the wild biotopes. Triatoma infestans (Klug
      1834) was exclusively found indoors and T. cruzi infected 60% of them. Triatoma
      sordida (Stal 1859) was mainly found in extradomestic ecotopes where trypanosome
      infection rate reached 12.7%. Serological study of 98 local people showed that
      29.6% were seroreactive; most of their houses were closed to wild biotopes
      colonized by T. sordida. Results indicate that there is an active T. infestans
      mediated transmission of Chagas disease in this zone that yields important human
      prevalence and that the populations of T. sordida in wild biotopes not only
      sustain the wild T. cruzi cycle but also represent an actual risk for people
      living in the area.

PMID- 11992146
TI  - Neutralizing antibodies to enterovirus 71 in Belem, Brazil.
AB  - Non-polio enteroviruses (Coxsackievirus A, Coxsackievirus B, Echovirus and EV 68
      72) which belong to the enterovirus (EV) genus, Picornaviridae family, may be
      responsible for acute flaccid paralysis, aseptic meningitis, myocarditis,
      hepatitis, pleurodinia, neonatal sepsis, hand, foot and mouth disease (HFMD) even
      though 50-80% of infections are asymptomatic. EV 71 has been responsible for
      outbreaks and epidemics of HFMD and acute neurologic disease justifying its study
      in our country. The aim of this study was to detect neutralizing antibodies
      (NtAb) to EV 71 in individuals up to 15 years of age living in Belem, State of
      Para, northern Brazil. Serum samples from 238 patients attending the Virology
      Sector of Evandro Chagas Institute in Belem, Brazil, were analyzed using
      microneutralization tests that included RD cells and BrCr strain. Overall 40.8%
      (97/238) of tested samples had NtAb to EV 71. Regarding the distribution per age
      group, 85.2% (92/108) of patients aged 0-3 years had no NtAb to this virus and
      69.2% of those 12 to 15 years of age were seropositive. These results confirm
      that EV 71 infection occurs in the city of Belem; and that a high rate of
      individuals in this study were infected aged 3 years and over and, when aged 15
      years nearly 70% had EV 71 NtAb.

PMID- 11992147
TI  - Ecological data of Travassosnema travassosi travassosi (Dracunculoidea:
      Guyanemidae) from the humour of the eyes of Acestrorhynchus lacustris from Tibagi
      River, Parana, Brazil.
AB  - Data obtained between 1990 and 1995 provide, for the first time, ecological
      information of the parasitic nematode Travassosnema travassosi travassosi Costa,
      Moreira & Oliveira, 1991 from Acestrorhynchus lacustris (Characiformes:
      Acestrorhynchidae) collected in the Tibagi River, Sertanopolis, Parana, Brazil.
      These nematode occurred with low prevalences (7.7% to 28.6%) and intensities (1
      to 3) during almost the whole year. The observation of mature females throughout
      the year indicate that liberation of larvae can occur during all the year around.
      This is the first report on the occurrence of T. travassosi travassosi inside the
      eyes. These nematodes were mostly located in humour of the eyes (87% of cases),
      being less frequently detected in tissues behind the eyes (13% of cases).

PMID- 11992148
TI  - Species diversity and flagellate infections in the sand fly fauna near Porto
      Grande, State of Amapa, Brazil (Diptera: Psychodidae. Kinetoplastida:
      Trypanosomatidae).
AB  - Forty-six species of Lutzomyia and one species of Brumptomyia were identified
      among 20,008 sand flies collected in central Amapa. L. squamiventris maripaensis,
      L. infraspinosa, L. umbratilis, and L. ubiquitalis accounted for 66% of the
      specimens caught in light traps, and L. umbratilis was the commonest of the 16
      species found on tree bases. Seven species of Lutzomyia including L. umbratilis
      were collected in a plantation of Caribbean pine. Sixty out of 511 female sand
      flies dissected were positive for flagellates. Among the sand flies from which
      Leishmania was isolated, promastigotes were observed in the salivary glands and
      foregut of 13 out of 21 females scored as having very heavy infections in the
      remainder of the gut, reinforcing the idea that salivary gland invasion may be
      part of the normal life cycle of Leishmania in nature. Salivary gland infections
      were detected in specimens of L. umbratilis, L. whitmani and L. spathotrichia.
      Parasites isolated from L. umbratilis, L. whitmani and also from one specimen of
      L. dendrophyla containing the remains of a bloodmeal, were compatible with Le.
      guyanensis by morphology and behaviour in hamsters.

PMID- 11992149
TI  - Trapping Triatominae in silvatic habitats.
AB  - Large-scale trials of a trapping system designed to collect silvatic Triatominae
      are reported. Live-baited adhesive traps were tested in various ecosystems and
      different triatomine habitats (arboreal and terrestrial). The trials were always
      successful, with a rate of positive habitats generally over 20% and reaching
      48.4% for palm trees of the Amazon basin. Eleven species of Triatominae belonging
      to the three genera of public health importance (Triatoma, Rhodnius and
      Panstrongylus) were captured. This trapping system provides an effective way to
      detect the presence of triatomines in terrestrial and arboreal silvatic habitats
      and represents a promising tool for ecological studies. Various lines of research
      are contemplated to improve the performance of this trapping system.

PMID- 11992150
TI  - A cladistic analysis of Inaequalium (Coscaron & Wygodzinsky, 1984), with
      information on geographical distribution (Diptera: Simuliidae).
AB  - The black flies of the genus Inaequalium present a Neotropical distribution, with
      Panama at the northern limit, and the Argentinian pampas at the southern, but do
      not occur in the Central Amazon. This study offers a cladistic analysis
      establishing a hypothesis of relationships between the species of Inaequalium. A
      total of 37 characters have been considered in order to establish the hypothetic
      phylogenetic relationships. Cerqueirellum (Py-Daniel, 1983) was considered as
      outgroup. Data were analyzed using Henning 86 version 1.5. Wich the i.e.* command
      and implicit enumeration a unique possible cladogram was obtained in Inaequalium
      with 52 steps, and a CI of 0.76 and RI of 0.81. Two well-defined clades was
      obtained in the resulting cladogram, the "botulibranchium" species-group,
      includes I. travassosi, I. souzalopesi, I. botulibranchium and I. petropoliense,
      and the "inaequale" species-group, includes I. rappae, I. nahimi, I. inaequale,
      I. leopoldense, I. subnigrum, I. diversibranchium, I. mariavulcanoae, I.
      nogueirai, I. beaupertuyi, I. clavibranchium and I. subclavibranchium.

PMID- 11992151
TI  - Rhodnius amazonicus Almeida, Santos & Sposina, 1973, bona species, close to R.
      pictipes Stal, 1872 (Heteroptera, Reduviidae, Triatominae).
AB  - The discovery of two atypical specimens of Rhodnius pictipes Stal, 1872 in French
      Guiana and the examination of the female holotype of R. amazonicus Almeida,
      Santos & Sposina, 1973, the only specimen of this species so far known, lead us
      to propose the rehabilitation of R. amazonicus synonymized with R. pictipes. The
      male is described for the first time and the female redescribed. Both external
      characters and genitalia distinguish R. amazonicus from R. pictipes. R.
      amazonicus shows affinities not only with pictipes but also with R. stali Lent,
      Jurberg & Galvao, 1993 and R. paraensis Sherlock, Guitton & Miles, 1977. A key is
      provided for these four species forming, in all likelihood, a natural group, i.e.
      the "pictipes group".

PMID- 11992152
TI  - Myxobolus absonus sp. n. (Myxozoa: Myxosporea) parasitizing pimelodus maculatus
      (siluriformes: Pimelodidae), a South American freshwater fish.
AB  - A new myxoporean species is described from a freshwater fish in Brazil. Myxobolus
      absonus sp. n. was found infecting Pimelodus maculatus captured in the river
      Piracicaba, State of Sao Paulo, Brazil. Cysts were found free in the opercular
      cavity. The spores are large (length--15.7 +/- 1.5 microns, width--10.2 +/- 0.7
      microns; mean +/- S.D.) and oval in shape, with the anterior end slightly
      pointed. The spore valves are relatively thin, smooth, and asymmetrical in a
      frontal view. The polar capsules are pyriform in shape, and unequal in size; the
      largest are 6.4 +/- 0.7 microns long and 3.6 +/- 0.5 microns wide, while the
      smallest are 4.2 +/- 0.6 microns long and 2.5 +/- 0.5 microns wide.

PMID- 11992153
TI  - Araucnephia iberaensis n. sp., a neotropical black fly with a peculiar
      distribution (Diptera-Simuliidae).
AB  - Araucnephia Wygodzinsky & Coscaron is a Neotropical black fly genus in which only
      one species from Central Chile is known. Another species has now been found in
      Corrientes province on the eastern side of the Ibera tropical swamps of
      Argentina, on the western border of the mountainous region of southern Brazil.
      This new species, A. iberaensis, is herein described and illustrated and
      information on its bionomics is recorded. It is an interesting species because
      previous to its discovery no black fly genus or subgenus from Central Chile
      region has been found in tropical areas, because these two regions are separated
      by the Monte and Pampas realms. Similarly, no Brazilian genus or subgenus has
      crossed the Andes mountains to Chile. A comparison with other Neotropical,
      Nearctic, Ethiopian (Afrotropical) and Australian Prosimuliini (sensu Crosskey &
      Howard) showed Araucnephia to be a valid taxon most closely related to
      Araucnephioides (sympatric in Chile). Araucnephia also shows great affinities
      with Lutzsimulium from Southeast Brazil and Argentina and Paracnephia from South
      Africa.

PMID- 11992154
TI  - Some morphological aspects of Cylicocyclus brevicapsulatus (Nematoda:
      Cyathostominae) parasite of horse.
AB  - This paper describes some morphological aspects of Cylicocyclus brevicapsulatus
      (Ihle, 1920) (Nematoda: Cyathostominae) from Equus caballus in Brazil. The worms
      were studied using an optical microscope (measurements and illustrations) and a
      scanning electron microscope for a more detailed examination of the external
      morphology. The buccal capsule is very short, with a very thin wall, and the
      dorsal gutter is absent. Other morphological aspects are described including
      measurement of the spicules and gubernaculum.

PMID- 11992155
TI  - First report of Lappetascaris lutjani Rasheed, 1965 (Nematoda, Ascaridoidea,
      Anisakidae) parasitizing Trachipterus arawatae (Pisces, Lampridiformes) on the
      Atlantic coast of Brazil.
AB  - New host and geographical records are reported for the nematode Lappetascaris
      lutjani Rasheed, 1965, parasitizing the marine fish Trachipterus arawatae Clark,
      1881 in Brazilian waters. Morphometric data and illustrations of the parasites
      are included.

PMID- 11992156
TI  - Additives and protein-DNA combinations modulate the humoral immune response
      elicited by a hepatitis C virus core-encoding plasmid in mice.
AB  - Humoral and cellular immune responses are currently induced against hepatitis C
      virus (HCV) core following vaccination with core-encoding plasmids. However, the
      anti-core antibody response is frequently weak or transient. In this paper, we
      evaluated the effect of different additives and DNA-protein combinations on the
      anti-core antibody response. BALB/c mice were intramuscularly injected with an
      expression plasmid (pIDKCo), encoding a C-terminal truncated variant of the HCV
      core protein, alone or combined with CaCl2, PEG 6000, Freund's adjuvant,
      sonicated calf thymus DNA and a recombinant core protein (Co. 120). Mixture of
      pIDKCo with PEG 6000 and Freund's adjuvant accelerated the development of the
      anti-core Ab response. Combination with PEG 6000 also induced a bias to IgG2a
      subclass predominance among anti-core antibodies. The kinetics, IgG2a/IgG1 ratio
      and epitope specificity of the anti-core antibody response elicited by Co. 120
      alone or combined with pIDKCo was different regarding that induced by the pIDKCo
      alone. Our data indicate that the antibody response induced following DNA
      immunization can be modified by formulation strategies.

PMID- 11992157
TI  - IgG anti-IgE autoantibodies in visceral leishmaniasis.
AB  - Procedures for IgG depletion in visceral leishmaniasis (VL) and schistosomiasis
      sera using Sepharose-protein G beads also deplete IgE. In this study, the
      presence of IgG anti-IgE autoantibodies in sera from patients with VL (n = 10),
      and hepatic-intestinal schistosomiasis (n = 10) and from healthy individuals (n =
      10) was investigated. A sandwich ELISA using goat IgG anti-human IgE to capture
      serum IgE and goat anti-human IgG peroxidase conjugate to demonstrate the binding
      of IgG to the IgE captured was performed. VL sera had higher titers (p < 0.05) of
      IgG anti-IgE autoantibodies (OD = 2.01 +/- 0.43) than sera from healthy
      individuals (OD = 1.35 +/- 0.16) or persons infected with Schistosoma mansoni (OD
      = 1.34 +/- 0.18). The immunoblotting carried out with eluates from Sepharose
      protein G beads used to deplete IgG from these sera and goat anti-human IgE
      peroxidase conjugate, showed a similar pattern of bands, predominating the 75 kDa
      epsilon-heavy chain and also polypeptides resulting from physiological enzymatic
      digestion of IgE. A frequent additional band immediately above 75 kDa was
      observed only in VL sera.

PMID- 11992158
TI  - Detection of hepatitis B virus antigens in paraffin-embedded liver specimens from
      the Amazon region, Brazil.
AB  - Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period
      from 1934 to 1967, were analyzed by immunohistochemical assays to detect
      hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material
      belongs to the Yellow Fever Collection, Department of Pathology, Instituto
      Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time
      according to clinical aspects and histopathological findings reporting viral
      hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79
      specimens, 69 were collected at the Labrea Region and the other 10 in difFerent
      other localities in the Amazon Region. The five micra thick histological slices
      were analyzed for the presence of hepatitis B surface antigen (HBsAg) and
      hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An
      immunofluorescence assay was applied to the detection of hepatitis D, yellow
      fever and dengue virus antigens. Nine (11.4%) histological samples were HBsAg
      reactive and 5 (6.3%) were HBcAg reactive. The oldest reactive sample was from
      1934. Viral antigens related to the other pathologies were not detected in this
      study. Our results confirm that the methodology described may be used to
      elucidate the aetiology of hepatitis diseases even after a long time of
      conservation of the specimens.

PMID- 11992159
TI  - A heminested polymerase chain reaction for the detection of Brazilian rabies
      isolates from vampire bats and herbivores.
AB  - A heminested-PCR (hn-PCR) using primers to the nucleoprotein-coding gene in a
      nested set was evaluated in the detection of Brazilian strains of rabies virus
      (RV). A representative number of RV nucleoprotein sequences belonging to genotype
      1 were aligned. Based on such alignment, primers were directed to highly
      conserved regions. All 42 clinical samples positive by both fluorescent antibody
      and mouse inoculation tests were also positive by the hn-PCR. Brain tissue that
      had been left to decompose, obtained from an experimentally inoculated mouse was
      tested by hn-PCR and yielded positive results. In conclusion, primers designed
      here were capable of amplifying Brazilian RV isolates obtained from a rural
      epidemiological cycle.

PMID- 11992160
TI  - Detection and characterization of rotavirus G and P types from children
      participating in a rotavirus vaccine trial in Belem, Brazil.
AB  - This study sought the characterization of rotaviruses in a trial with a
      tetravalent rhesus-human rotavirus vaccine in Belem, Brazil in children who
      received three doses of vaccine or placebo in the 1st, 3rd and 5th months of
      life. Rotavirus electropherotypes, subgroups, G serotypes, G, [P] and [P], G
      genotypes were determined in 93.3%, 95.9%, 93.3%, 73.3%, 95.5% and 92.2% of
      isolates, respectively. Serotypes G1, G2 and G4 were detected in 58.9%, 30% and
      4.4% of the cases, respectively. Rotavirus genotype G5 was detected for the first
      time in Northern region in 4.4% of the infections. Rotavirus genotypes P[8],
      P[4], P[6] and P[8 + 6] were detected in 54.5%, 26.7%, 12.2%, and 2.2% of the
      cases, respectively. The predominant genotypes were P[8], G1 and P[4], G2 with
      53% and 26.6% of the infections, respectively. Unusual strains accounted for
      20.5% including P[4], G1, P[6], G1, P[6], G4, P[6], G5, P[8], G2, P[8], G5. Mixed
      infections involving P[8 + 6], G2 and P[8 + 6], G1 were also noted. The neonatal
      P[6] strains associated with diarrhea were detected among children aged 9-24
      months. To our knowledge, this study represents the first in Brazil to analyse,
      on molecular basis, rotavirus genotypes from children participating in a
      rotavirus vaccine trial. These results are of potential importance regarding
      future rotavirus vaccination strategies in Brazil.

PMID- 11992161
TI  - Frequency of Strongyloides stercoralis infection in alcoholics.
AB  - Several studies have shown that chronic alcoholics have increased susceptibility
      to infections due to higher exposure to infectious agents as well as breakdown in
      their immune defenses. As Strongyloides stercoralis infection is usually more
      relevant in immunocompromised patients, the aim of this study was to evaluate the
      frequency of S. stercoralis infection in alcoholics. Thus, coproparasitological
      examination was carried out in 145 subjects, from which 45 were chronic
      alcoholics (mean age of 45.7 +/- 11.0 years), 10 were nonalcoholic cirrhotic
      patients (mean age of 50.2 +/- 13.1 years), and 90 were asymptomatic nonalcoholic
      subjects (mean age of 46.7 +/- 10.1 years), which served as controls. From the
      alcoholics, 9 had hepatic cirrhosis, 9 had chronic pancreatitis and 27 had
      neither cirrhosis nor pancreatitis. For the diagnosis of strongyloidiasis, the
      Baermann-Moraes and Lutz methods were used in three fecal samples from each
      subject. Samples were collected at alternated days, and three slides of each
      sample were analyzed for each method, thus totalizing 2,610 slides examined. The
      frequency of strongloidiasis in the total alcoholic group (33.3%) and in the
      subgroups of alcoholics, i.e., patients with hepatic cirrhosis (44.4%), with
      chronic pancreatitis (33.3%), and those with no cirrhosis or pancreatitis (29.6%)
      was statistically higher than that found in the control group (5.5%). None of the
      individuals with nonalcoholic hepatic cirrhosis had S. stercoralis infection. Our
      results showed that the chronic alcoholism itself is an important factor that
      predisposes to strongyloidiasis.

PMID- 11992162
TI  - An autochthonous case of Echinococcus vogeli Rausch & Bernstein, 1972 polycystic
      echinococcosis in the state of Rondonia, Brazil.
AB  - The present case report refers to a patient from the State of Rondonia, North
      region of Brazil, attended with clinical suspicion of hepatic echinococcosis.
      Examination by imaging (ultrasonography and computerized tomography) revealed a
      conglomerate of cystic lesions, with mobile contents within the cyst. The
      serology (immunoblot) for Echinococcus sp. was positive (21 and 31 kDa bands).
      This case is the first reported in Rondonia, suggesting the need to investigate
      the polycystic echinococcosis in individuals with hepatic cysts from areas of
      tropical forest and hunting habits where wild life was present as wild dogs, cats
      and rodents, particularly Agouti paca (paca) and Dasyprocta aguti (agouti).

PMID- 11992163
TI  - Cercarial chaetotaxy and sex differentiation of Schistosoma mansoni deriving from
      humans and Nectomys squamipes (Muridae: Sigmondontinae) in Brazil.
AB  - A comparative study was made between sympatric isolates of Schistosoma mansoni:
      one from a wild rodent (R) Nectomys squamipes and another one from humans (H)
      isolated from a low endemic schistosomiasis transmission area in Brazil. Our
      purpose was to detect differences between them concerning chaetotaxy (number and
      pattern of distribution of the argentophilic papillae) of the cercariae by means
      of silver impregnation. No significant difference (x > 0.05) between isolates was
      noted. Nevertheless, a significant difference (x < 0.05) was observed in the
      cercarial index (ratio of the distance between the first and the second
      preacetabular papillane and the distance between the first and the second dorsal
      preacetabular papillae) of male and female cercariae in both isolates. Males
      presented a greater cercarial index than females. By means of multivariate
      analysis, male cercariae were distinguished from female cercariae through the
      following characteristics: average number of dorsal papillae on the right
      quadrant, average number of ventral middle papillae on the right quadrant (H
      isolate) and average number of dorsal middle papillae on the left quadrant (R
      isolate). The results suggest that R and H isolates belong to the same population
      that could complete its life cycle in rodent-snail-rodent fashion.

PMID- 11992164
TI  - Activity of tabanids (Insecta: Diptera: Tabanidae) attacking the reptiles Caiman
      crocodilus (Linn.) (Alligatoridae) and Eunectes murinus (Linn.) (Boidae), in the
      central Amazon, Brazil.
AB  - Tabanid females are better known as hematophagous on man and other mammals, and
      linked to mechanical transmission of parasites. The association between tabanids
      and reptiles is poorly known, but has been gaining more corroboration through
      experiments and occasional observation in the tropics. The present study was
      conducted at a military base (CIGS/BI-2), situated 54 km from Manaus, Amazonas,
      in a small stream in a clearing (02 degrees 45'33"S; 59 degrees 51'03"W).
      Observations were made monthly, from April 1997 to March 1998, during two
      consecutive days. At the same time, other vertebrate animals were offered,
      including humans. However in this paper only data obtained on a common caiman,
      Caiman crocodilus (Linn.), and an anaconda, Eunectes murinus (Linn.), in diurnal
      observations from 05:30 a.m. to 18:30 p.m., will be discussed. A total of 254
      tabanid specimens were collected, 40 from the anaconda and 214 from the caiman.
      Four tabanid species were recorded on these two reptiles: Stenotabanus cretatus
      Fairchild, S. bequaerti Rafael et al., Phaeotabanus nigriflavus (Krober) and
      Tabanus occidentalis Linn. Diurnal activities showed species-specific patterns.
      The first three species occurred only in the dry season. T. occidentalis occurred
      during the whole observation period, and with increased frequency at the end of
      the dry season. We observed preferences for body area and related behavior of the
      host. Observations on the attack of tabanids on one dead caiman are also
      presented.

PMID- 11992165
TI  - Flies (Calliphoridae, Muscidae) and beetles (Silphidae) from human cadavers in
      Cali, Colombia.
AB  - Adult specimens of Cochliomyia macellaria, Chrysomya megacephala, Ch. rufifacies,
      Lucilia sp. (Calliphoridae), Musca domestica (Muscidae), Oxelytrum discicolle
      (Silphidae) and Sarcophagidae were recovered from 12 human cadavers in Cali,
      Valle, Colombia. Information regarding these findings is presented.

PMID- 11992166
TI  - Some Streblidae and Nycteribiidae (Diptera: Hippoboscoidea) from Maraca Island,
      Roraima, Brazil.
AB  - Fourteen species in five genera of Streblidae and two species in two genera of
      Nycteribiidae, collected in Maraca Island, State of Roraima, Brazil are presented
      with comments on bat hosts and geographical distribution. A total of 42 specimens
      of Diptera and 17 bats were captured from 1987 to 1988, integrating the "Maraca
      Project". All species of ectoparasites represent new geographic records for
      Roraima.

PMID- 11992167
TI  - Scientist and policy-maker response types and times in suburban watersheds.
AB  - Differences between scientist and policy-maker response types and times, or the
      "how" and "when" of action, constrain effective water resource management in
      suburbanizing watersheds. Policy-makers are often rushed to find a single policy
      that can be applied across an entire, homogeneous, geopolitical region, whereas
      scientists undertake multiyear research projects to appreciate the complex
      interactions occurring within heterogeneous catchments. As a result, watershed
      management is often practiced with science and policy out of synch. Meanwhile,
      development pressures in suburban watersheds create changes in the social and
      physical fabric and pose a moving target for science and policy. Recent and
      anticipated advances in the scientific understanding of urbanized catchment
      hydrology and pollutant transport suggest that management should become
      increasingly sensitive to spatial heterogeneities in watershed features, such as
      soil types, terrain slopes, and seasonal watertable profiles. Toward this end,
      policy-makers should encourage funding scientific research that characterizes the
      impacts of these watershed heterogeneities within a geopolitical zoning and
      development framework.

PMID- 11992168
TI  - Preparation and implementation of seven ecological compensation plans for Dutch
      highways.
AB  - First-generation compensation plans (CPs) for Dutch highway projects have been
      evaluated with respect to implementation of the compensation principle (1993),
      which aims to counterbalance the adverse ecological impacts of large-scale
      development projects. Decision-making on the seven projects took place between
      1993 and 1995. Specifically, we considered: (a) the processes employed to prepare
      and implement the compensation plans; (b) the methods used to identify, plan, and
      execute the compensation measures; and (c) the results yielded by these methods.
      We conclude that the CPs were prepared fairly uniformly, particularly in terms of
      the processes and methodologies used to derive compensation measures. Five of the
      seven CPs had become operational by 2001 and initial experience is now being
      gained on land acquisition and transfer of compensation sites to nature
      conservation trusts. Further progress of CPs is likely to be seriously hampered
      by growing demand for land for development in general and associated increases in
      real estate prices. Several problems are addressed and recommendations made with
      respect to: (a) developing a legal basis for the compensation principle; (b) the
      relationship with re-allotment projects; (c) estimation of compensation costs;
      (d) an annual bias of CP budgets to account for rising costs; (e) contingency
      measures; and (f) criteria for CP (ex-post) evaluation.

PMID- 11992169
TI  - Conservation and development projects in the Brazilian Amazon: lessons from the
      Community Initiative Program in Rondonia.
AB  - Community-based conservation and development has become the prevailing
      programmatic paradigm of conservation organizations and development donors over
      the last 20 years, spawning a myriad of integrated conservation and development
      projects (ICDP) around the world. Appealing for its ambitious aspiration to
      harmonize sustainable economic development at the local level with the
      conservation of legally established protected areas (e.g., parks and reserves),
      the ICDP approach recently has drawn criticism from conservation biologists for
      failing to ensure adequate protection of biodiversity. Development planners and
      economists have also raised questions about the financial sustainability of ICDPs
      in practice and the replicability of the model from highly local contexts to
      larger regional scales. This paper briefly reviews the central elements of the
      concept of integrated conservation and development and the emerging debate over
      its effectiveness. A description of the Community Initiative Program (CIP), a
      pilot program of the Rondonia Natural Resources Management project (PLANAFLORO)
      in the western Brazilian Amazon state of Rondonia, follows. The CIP is a
      significant experiment because it boldly attempted to apply the principles of
      ICDP to the regional scale involving numerous different communities in one
      program simultaneously. Based on the author's mid-term review of the CIP in 1999,
      the development and conservation impacts of the program are considered. While the
      CIP has not significantly curbed the degradation of protected areas in Rondonia
      as intended, the evidence suggests lower rates of deforestation in municipios
      (i.e. counties) with the highest concentrations of CIP projects. Although the
      economic development impacts are mixed, approximately 50% of the projects
      delivered tangible benefits to local communities. Lessons learned from the CIP
      are presented in the final section. Among the lessons learned from the CIP,
      detailed in the final section, are several that will be familiar to other ICDP
      evaluators: the importance of thematic coherence in initial project design, the
      need for explicit attention on environmental conservation objectives, deficient
      institutional capacity of implementing organizations, inadequate attention to
      women's concerns and roles in community projects, and lack of technical criteria
      for measuring project sustainability.

PMID- 11992170
TI  - Human impacts on the stream-groundwater exchange zone.
AB  - Active exchanges of water and dissolved material between the stream and
      groundwater in many porous sand- and gravel-bed rivers create a dynamic ecotone
      called the hyporheic zone. Because it lies between two heavily exploited
      freshwater resources-rivers and groundwater-the hyporheic zone is vulnerable to
      impacts coming to it through both of these habitats. This review focuses on the
      direct and indirect effects of human activity on ecosystem functions of the
      hyporheic zone. River regulation, mining, agriculture, urban, and industrial
      activities all have the potential to impair interstitial bacterial and
      invertebrate biota and disrupt the hydrological connections between the hyporheic
      zone and stream, groundwater, riparian, and floodplain ecosystems. Until
      recently, our scientific ignorance of hyporheic processes has perhaps excused the
      inclusion of this ecotone in river management policy. However, this no longer is
      the case as we become increasingly aware of the central role that the hyporheic
      zone plays in the maintenance of water quality and as a habitat and refuge for
      fauna. To fully understand the impacts of human activity on the hyporheic zone,
      river managers need to work with scientists to conduct long-term studies over
      large stretches of river. River rehabilitation and protection strategies need to
      prevent the degradation of linkages between the hyporheic zone and surrounding
      habitats while ensuring that it remains isolated from toxicants. Strategies that
      prevent anthropogenic restriction of exchanges may include the periodic release
      of environmental flows to flush silt and reoxygenate sediments, maintenance of
      riparian buffers, effective land use practices, and suitable groundwater and
      surface water extraction policies.

PMID- 11992171
TI  - Road traffic and nearby grassland bird patterns in a suburbanizing landscape.
AB  - An extensive road system with rapidly increasing traffic produces diverse
      ecological effects that cover a large land area. Our objective was to evaluate
      the effect of roads with different traffic volumes on surrounding avian
      distributions, and its importance relative to other variables. Grassland bird
      data (5 years) for 84 open patches in an outer suburban/rural landscape near
      Boston were analyzed relative to: distance from roads with 3000-8000 to >30,000
      vehicles/day; open-habitat patch size; area of quality microhabitat within a
      patch; adjacent land use; and distance to other open patches. Grassland bird
      presence and regular breeding correlated significantly with both distance from
      road and habitat patch size. Distance to nearest other open patch, irrespective
      of size, was not significant. Similarly, except for one species, adjacent land
      use, in this case built area, was not significant. A light traffic volume of 3000
      8000 vehicles/day (local collector street here) had no significant effect on
      grassland bird distribution. For moderate traffic of 8000-15,000 (through
      street), there was no effect on bird presence although regular breeding was
      reduced for 400 m from a road. For heavier traffic of 15,000-30,000 (two-lane
      highway), both bird presence and breeding were decreased for 700 m. For a heavy
      traffic volume of > or =30,000 vehicles/day (multilane highway), bird presence
      and breeding were reduced for 1200 m from a road. The results suggest that avian
      studies and long-term surveys near busy roads may be strongly affected by traffic
      volume or changes in volume. We conclude that road ecology, especially the
      effects extending outward >100 m from roads with traffic, is a sine qua non for
      effective land-use and transportation policy.

PMID- 11992172
TI  - Environmental evaluation of subdivision site developments.
AB  - An environmental evaluation was performed at 16 subdivision sites within four
      communities in east-central Michigan. The primary objective was to evaluate the
      fit between environmental ordinances and the physical/environmental conditions to
      which they were applied. An environmental response index was developed with
      indicators to assess water, soil, slope, development density, roads, vegetation,
      and ecology. Water-related indicators achieved the highest scores, while soil
      related indicators scored the poorest, with generally poor performance across all
      indicators. The poor performance indicates there are problems in the ability of
      environmental ordinances developed at broader jurisdictional scales (e.g., the
      state) to address the existing environmental conditions at smaller geographic
      scales (subdivisions within communities). Two key problems include the lack of
      scientific specificity in the broader state-level ordinances and the lack of
      local expertise and/or resources to monitor the environment.

PMID- 11992173
TI  - Recommended design for more accurate duplication of natural conditions in salt
      marsh creation.
AB  - Construction of 653 ha of salt marsh habitat from dredged material near the
      Aransas National Wildlife Refuge, Texas, has been proposed, with the goal of
      increasing the area of habitat available to endangered whooping cranes ( Grus
      americana). We assessed prototype created wetlands, and their similarity to
      natural reference sites, in terms of topography, vegetation, and hydrology. The
      created sites were steeply sloped relative to natural sites and were dominated by
      monotypic stands of Spartina alterniflora. Natural sites were dominated by
      vegetation more tolerant of desiccation and hypersalinity and by unvegetated salt
      pans. Differences in vegetation communities and distributions of habitat types
      resulted from efforts to enhance habitat diversity in created marsh cells through
      manipulation of marsh topography. However, the scale at which this diversity
      occurred in natural marsh of the study area was not considered. When constructing
      wetlands in cellular configurations, we recommend creation of large complexes of
      adjoining, hydrologically linked, cells wherein the desired habitat diversity is
      created at the scale of the entire complex, rather than within a single cell.
      Suggested design modifications would increase the similarity of created marshes
      to natural reference sites, potentially improving habitat function.

PMID- 11992174
TI  - Consequences of livestock grazing on water quality and Benthic algal biomass in a
      Canadian natural grassland plateau.
AB  - The effects of livestock grazing on selected riparian and stream attributes,
      water chemistry, and algal biomass were investigated over a two-year period using
      livestock enclosures and by completing stream surveys in the Cypress Hills
      grassland plateau, Alberta, Canada. Livestock enclosure experiments, partially
      replicated in three streams, comprised four treatments: (1) early season
      livestock grazing (June-August), (2) late season livestock grazing (August
      September), (3) all season grazing (June-September), and (4) livestock absent
      controls. Livestock grazing significantly decreased streambank stability, biomass
      of riparian vegetation, and the extent to which aquatic vegetation covered the
      stream channels compared with livestock-absent controls. Water quality
      comparisons indicated significant differences among the four livestock grazing
      treatments in Battle and Graburn creeks but not in Nine Mile Creek. In Graburn
      Creek, the concentration of total phosphorus in the all-season livestock grazing
      treatment was significantly higher than that in the livestock-absent control, and
      the early season and late season grazing treatments. Concentrations of soluble
      reactive phosphorus in the all-season livestock grazing treatment also exceeded
      that in livestock-absent control. In contrast, differences in water quality
      variables in the remaining 22 comparisons (i.e., 22 of the total 24 comparisons)
      were minor even when differences were statistically significant. Effects of
      livestock grazing on algal biomass were variable, and there was no consistent
      pattern among creeks. At the watershed scale, spatial variation in algal biomass
      was related (P < 0.05) with concentrations of NO(2)(-) + NO(3) (-) and soluble
      reactive phosphorus in two of the four study creeks. Nutrient diffusing substrata
      experiments showed that algal communities were either nitrogen-limited or not
      limited by nutrients, depending on stream and season.

PMID- 11992175
TI  - Fuzzy decision analysis for integrated environmental vulnerability assessment of
      the mid-Atlantic Region.
AB  - A fuzzy decision analysis method for integrating ecological indicators was
      developed. This was a combination of a fuzzy ranking method and the analytic
      hierarchy process (AHP). The method was capable of ranking ecosystems in terms of
      environmental conditions and suggesting cumulative impacts across a large region.
      Using data on land cover, population, roads, streams, air pollution, and
      topography of the Mid-Atlantic region, we were able to point out areas that were
      in relatively poor condition and/or vulnerable to future deterioration. The
      method offered an easy and comprehensive way to combine the strengths of fuzzy
      set theory and the AHP for ecological assessment. Furthermore, the suggested
      method can serve as a building block for the evaluation of environmental
      policies.

PMID- 11992176
TI  - Application of sediment quality guidelines in the assessment and management of
      contaminated surficial sediments in Port Jackson (Sydney Harbour), Australia.
AB  - Sediments in the Port Jackson estuary are polluted by a wide range of toxicants
      and concentrations are among the highest reported for any major harbor in the
      world. Sediment quality guidelines (SQGs), developed by the National
      Oceanographic and Atmospheric Administration (NOAA) in the United States are used
      to estimate possible adverse biological effects of sedimentary contaminants in
      Port Jackson to benthic animals. The NOAA guidelines indicate that Pb, Zn, DDD,
      and DDE are the most likely contaminants to cause adverse biological effects in
      Port Jackson. On an individual chemical basis, the detrimental effects due to
      these toxicants may occur over extensive areas of the harbor, i.e., about 40%,
      30%, 15% and 50%, respectively. The NOAA SQGs can also be used to estimate the
      probability of sediment toxicity for contaminant mixtures by determining the
      number of contaminants exceeding an upper guideline value (effects range medium,
      or ERM), which predicts probable adverse biological effects. The exceedence
      approach is used in the current study to estimate the probability of sediment
      toxicity and to prioritize the harbour in terms of possible adverse effects on
      sediment-dwelling animals. Approximately 1% of the harbor is mantled with
      sediment containing more than ten contaminants exceeding their respective ERM
      concentrations and, based on NOAA data, these sediments have an 80% probability
      of being toxic. Sediment with six to ten contaminants exceeding their respective
      ERM guidelines extend over approximately 4% of the harbor and have a 57%
      probability of toxicity. These areas are located in the landward reaches of
      embayments in the upper and central harbor in proximity to the most
      industrialised and urbanized part of the catchment. Sediment in a further 17% of
      the harbor has between one and five exceedences and has a 32% probability of
      being toxic. The application of SQGs developed by NOAA has not been tested
      outside North America, and the validity of using them in Port Jackson has yet to
      be demonstrated. The screening approach adopted here is to use SQGs to identify
      contaminants of concern and to determine areas of environmental risk. The
      practical application and management implications of the results of this
      investigation are discussed.

PMID- 11992177
TI  - Inventory of ocean monitoring in the Southern California Bight.
AB  - Monitoring of the ocean environment in southern California, USA, has been
      conducted by a diverse array of public and private organizations with different
      motivations, working on a variety of spatial and temporal scales. To create a
      basis from which to integrate information from these diverse programs, we
      conducted an inventory of ocean monitoring activities in the Southern California
      Bight to address the following questions: (1) How much money is being expended
      annually on marine monitoring programs? (2) Which organizations are conducting
      the most monitoring? (3) How are resources allocated among the different types of
      monitoring programs? This inventory focused on programs existing, or those
      expected to be in existence, for at least 10 years and that were active at any
      time between 1994 and 1997. For each program identified for inclusion in this
      study, information was collected on the number of sites, sampling intensity,
      parameters measured, and methods used. Levels of effort were translated into cost
      estimates based upon a market survey of local consulting firms. One hundred
      fourteen marine monitoring programs, conducted by 65 organizations and costing US
      $31 million annually, were identified. Most of the effort (81 programs, 65% of
      samples, 70% of costs) was expended by ocean dischargers as part of their
      compliance with National Pollutant Discharge Elimination System (NPDES) permit
      requirements. Federal programs (11 programs, 25% of samples, 10% of total
      expenditures) expended more than state or local government programs. More than
      one quarter of monitoring expenditures were conducted to measure concentrations
      and mass of effluent inputs to the ocean. The largest effort expended on
      receiving water monitoring was for measuring bacteria, followed by sediments,
      fish/shellfish, water quality, and intertidal habitats. The large level of
      expenditures by individual agencies has presented opportunities for integrating
      small, site-specific ocean monitoring programs into regional- and national-scale
      monitoring and assessment programs.

PMID- 11992178
TI  - Stream restoration and enhancement projects: is anyone monitoring?
AB  - Declines in salmon stocks and general watershed health in Washington State, USA,
      have led to an increase in stream restoration and enhancement projects initiated
      throughout the state. The increasing number of projects has also raised questions
      regarding the monitoring of these efforts. Project managers receiving hydraulic
      project approvals (HPAs) were surveyed to determine whether monitoring was taking
      place on their projects. About half the project managers surveyed reported the
      collection of baseline data and the use of biological, physical, chemical, or
      other water quality measures for their projects. Of those who reported collection
      of monitoring data, only 18% indicated that monitoring was required. Respondents
      were also asked to rank the importance of various project goals on a Likert
      scale. Project managers with projects focusing on "engineering" goals (e.g.,
      roadbed stabilization) were less likely than other project managers to collect
      baseline monitoring data. Project managers with projects focusing on
      "restoration/ecological" or "fisheries" goals were more likely than other project
      managers to collect monitoring measures. Although monitoring appears to be taking
      place in slightly more than half of the projects surveyed, the nature of the data
      collected varies widely across projects, and in most cases the monitoring effort
      is voluntary. This suggests that project sponsors, funders, and managers must
      consider the issues involved in requiring appropriate monitoring, establishing
      standardized monitoring guidelines, the time frames in which to monitor,
      providing other incentives for conducting monitoring, and ensuring adequate
      funding for monitoring efforts.

PMID- 11992180
TI  - A clinical evaluation of tazarotene 0.1% gel, with and without a high- or mid
      high-potency corticosteroid, in patients with stable plaque psoriasis.
AB  - BACKGROUND: Several clinical trials have established the benefit of using a
      topical corticosteroid in conjunction with tazarotene gel in the treatment of
      plaque psoriasis. However, there is little information comparing the relative
      benefits of different corticosteroids, or different formulations of
      corticosteroids, when used adjunctively with tazarotene. OBJECTIVE: This study
      was designed to compare the clinical benefits achieved with each of six commonly
      prescribed high- or mid-high-potency corticosteroid creams and ointments applied
      in conjunction with tazarotene 0.1% gel in the treatment of patients with stable
      plaque psoriasis. METHODS: A 12-week, multicenter, investigator-masked,
      randomized, parallel-group study was performed with more than 200 patients who
      were randomly assigned to regimens of tazarotene 0.1% gel alone, tazarotene plus
      a high-potency topical corticosteroid (fluocinonide 0.05% ointment, mometasone
      furoate 0.1% ointment, or diflorasone diacetate 0.05% ointment), or tazarotene
      plus a mid-high-potency topical corticosteroid (betamethasone dipropionate 0.05%
      cream, fluticasone propionate 0.005% ointment, or diflorasone diacetate 0.05%
      cream). All medications were to be applied once daily: corticosteroids in the
      morning, tazarotene gel in the evening. At assessment visits, physicians made an
      overall evaluation of the patient's psoriasis and graded global improvement,
      plaque elevation, scaling, erythema, and pruritus. Patients also rated their
      treatment in terms of efficacy, tolerability, and satisfaction. RESULTS: The best
      performing steroid was betamethasone dipropionate 0.05% cream (a mid-high-potency
      steroid), followed by mometasone furoate 0.1% ointment (a high-potency steroid)
      and diflorasone diacetate 0.05% ointment (a high-potency steroid). Maximum
      improvements were achieved within 8 weeks. The best-tolerated regimen was
      tazarotene plus mometasone furoate 0.1% ointment and the optimal balance between
      efficacy and tolerability was achieved with this regimen. CONCLUSION: Some
      steroids are considerably more effective than others in optimizing the efficacy
      and tolerability of tazarotene therapy. With a suitable combination regimen, the
      duration of initial therapy (before maintenance therapy is started) need not be
      prolonged.

PMID- 11992181
TI  - Chronic pruritus associated with Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori is an established cause of gastritis and has been
      implicated in extradigestive diseases. OBJECTIVE: To investigate the role of H.
      pylori in patients with unexplained refractory pruritus. METHODS: Ten patients
      with severe pruritus unresponsive to conventional therapy were evaluated for
      active H. pylori infection by H. pylori serology followed by either
      esophagogastroduodenoscopy (EGD) or urea breath test. Of the 10 patients, 8 were
      found to have active infection. All 10 received anti-H. pylori antibiotic therapy
      and were reevaluated for relief of pruritus. RESULTS: Of 8 patients with active
      H. pylori infection, 87.5% (7/8) had some type of pruritus relief after triple
      therapy. Of these, 62.5% (5/8) had complete relief and 25% (2/8) had temporary
      relief of pruritus. The remaining 12.5% (1/8) did not respond. Two control
      patients without active H. pylori infection had no relief of pruritus with
      therapy. CONCLUSIONS: We have identified a population of patients with refractory
      pruritus and active H. pylori infection whose pruritus resolved after eradication
      of H. pylori.

PMID- 11992182
TI  - Transformation in mycosis fungoides: the role of methotrexate.
AB  - BACKGROUND: Large cell transformation in patients with mycosis fungoides (MF) has
      been well reported in the literature. Although the risk factors have not been
      clearly elucidated, advanced stage seems to be associated with a higher incidence
      of transformation. Because MF is a rare disorder, little is known about the
      influence of other factors such as immunosuppressive therapy in the occurrence of
      transformation. OBJECTIVE: We questioned the role of methotrexate (MTX) in the
      transformation of MF to large cell lymphoma (LCL). METHODS: We identified all
      patients with MF who were registered in our cutaneous lymphoma database.
      Transformation was defined by the presence of large cells exceeding 25% of the
      infiltrate in at least one skin biopsy. In one patient, we followed the
      histologic, immunophenotypic, and genotypic changes taking place as
      transformation occurred. RESULTS: A total of 134 patients with MF were
      identified. Of 21 patients who received MTX, 3 transformed, and of the 113
      patients in the non-MTX group, only 2 transformed. The incidence of
      transformation in the patients who received MTX was significantly higher than in
      those who did not receive the drug (14.3% vs. 1.8%; p = 0.03). This significance
      was maintained, even after controlling for stage and sex. For one patient who
      transformed, we demonstrated an identical dominant T-cell clone in all skin
      specimens, including the large cell lymphoma. CONCLUSION: Our results demonstrate
      a significant association between MTX exposure and transformation to LCL in
      patients with MF. In light of the small sample size, short followup of patients,
      and the inherent tendency of mycosis fungoides to transform, the role for MTX in
      transformation is unproven and needs to be confirmed in a multicenter study.

PMID- 11992183
TI  - Extragenital bowenoid papulosis associated with atypical human papillomavirus
      genotypes.
AB  - BACKGROUND: Bowenoid papulosis typically appears as grouped violaceous or red
      brown papules in the genital or perianal regions and clinically resembles
      condylomata acuminata. Isolated extragenital bowenoid papulosis is rare and has
      been reported in only a few case reports. OBJECTIVES: A 51-year-old
      immunocompetent, healthy woman had two solitary papules on the elbow; a 41-year
      old HIV-positive man had a solitary cutaneous plaque on the abdomen. No genital,
      periungual, or other extragenital sites of involvement were noted in either
      patient. The diagnosis was confirmed histologically in both cases. Lesional skin
      from the female patient was tested with the Digenehybrid HPV DNA assay and was
      positive for a mixture of low-risk HPV subtypes (6, 11, 42, 43, 44). Lesional
      skin from the male patient was tested with polymerase chain reaction (PCR).
      Consensus primers targeted for the HPV L1 region, which is a highly conserved
      sequence common to more than 20 HPV subtypes encoding a viral capsid protein,
      were used. PCR using the consensus primers was positive, but type-specific probes
      for HPV types 6, 11, 16, 18, 45, 31, 33, 35, and 39 were negative. CONCLUSIONS:
      To our knowledge, our male patient represents the first case of isolated bowenoid
      papulosis of the abdominal skin. Isolated upper-extremity bowenoid papulosis in
      our female patient is also a unique case in both location and involvement of low
      risk HPV types (6, 11, 42, 43, 44), which have not been previously associated
      with extragenital bowenoid papulosis.

PMID- 11992184
TI  - Acute generalized exanthematous pustulosis induced by oral fluconazole.
AB  - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a generalized,
      nonfollicular, pustular eruption of the skin associated with fever and
      leukocytosis. The cause of AGEP has mainly been attributed to drugs. OBJECTIVE:
      We report a unique case of AGEP in a 75-year-old male caused by oral fluconazole.
      We include clinical as well as histological illustrations of our case.
      CONCLUSION: Based on a current literature search using the MEDLINE electronic
      database, this is the first reported case of AGEP arising from use of oral
      fluconazole. The clinical presentation, clinical course, and histology are
      consistent with prior reports of AGEP resulting from other drugs. AGEP should be
      considered a possible complication of oral fluconazole treatment.

PMID- 11992185
TI  - Induction of dramatic hyperpigmentation in a patient with generalized lichen
      planus treated with re-PUVA.
AB  - BACKGROUND: Retinoids plus PUVA (re-PUVA) may be used in the treatment of lichen
      planus in cases that do not respond to monotherapy. Hyperpigmentation is a
      potential side effect of re-PUVA therapy. OBJECTIVE: A case of remarkably intense
      transient hyperpigmentation secondary to re-PUVA therapy is presented. METHODS
      AND RESULTS: An 18-year-old male with lichen planus who had been taking
      isotretinoin 80 mg per day for seven days developed an exaggerated
      hyperpigmentation following the third dose of PUVA. CONCLUSION: As the
      hyperpigmentary reaction did not occur until the third PUVA dose, which was near
      the steady state of isotretinoin, this case may illustrate a case of
      photosensitization secondary to isotretinoin alone or isotretinoin in
      combination.

PMID- 11992186
TI  - A review of antibiotics in dermatology.
AB  - BACKGROUND: Since the early 1930s when antibiotics were first introduced, they
      have revolutionized the way physicians treat infections. Skin conditions from
      acne to leprosy, which were once shunned by society, are now easily treated with
      oral antibiotics. OBJECTIVE: Antibiotics are chemicals derived from bacteria and
      fungi that uniquely have antibacterial action. The most notable example is
      penicillin, which is derived from a mold. With hundreds of antibiotics available
      to the practicing physician, improper use of these drugs has become widespread
      and expensive and has spawned resistant strains. For the dermatologist,
      antibiotics are vital weapons in the drug armamentarium for treating various skin
      conditions. CONCLUSION: This review explores the newest and most common oral,
      parenteral, and topical antibiotics used in dermatology, their indications,
      adverse effects, dosage, and spectrum of activity. Furthermore, systemic
      antibacterial prophylaxis and vaccines pertinent to dermatology are discussed.
      The penicillins, cephalosporins, tetracyclines, macrolides, fluoroquinolones,
      sulfonamides, aminoglycosides, lincosamides, folate inhibitors, and a new
      synthetic class of drugs, the oxazolidinones, are reviewed. These antibiotics are
      used to treat a variety of organisms.

PMID- 11992188
TI  - Time perception in boys with attention-deficit/hyperactivity disorder according
      to time duration, distraction and mode of presentation.
AB  - In a recent theoretical model of attention-deficit/hyperactivity disorder (ADHD),
      Barkley (1997a) predicted that ADHD children experience impairments in their
      psychological sense of time. This was demonstrated in a series of experiments by
      Barkley, Koplowicz, Anderson, and McMurray (1997). The present study sought to
      investigate the effects of ADHD subtype, stimulus duration, mode of presentation
      (visual versus auditory) and distractors on the performance of a simple time
      reproduction task. Data were obtained from 44 ADHD children (14 predominantly
      inattentive and 30 combined type) and 44 age-matched Controls using the Time
      Perception Application version 1.0 (Barkley, University of Massachusetts Medical
      Center, 1998). Results revealed that the ADHD children made significantly larger
      errors on Visual time reproduction tasks than the Controls, regardless of ADHD
      subtype or the presence of distractors. Furthermore, ADHD children were more
      likely to overestimate the shorter time intervals (0.5 and 2 s) and underestimate
      the longer time intervals (3, 4 and 6 s) relative to Controls. No group
      differences were observed on the auditory time reproduction task, with both ADHD
      and Control groups consistently underestimating the durations to be reproduced.
      The results of this study provide further support for the prediction that
      children with ADHD have an impaired sense of time.

PMID- 11992189
TI  - Rapid automatized naming in children referred for evaluation of heterogeneous
      learning problems: how specific are naming speed deficits to reading disability?
AB  - Because the Rapid Automatized Naming (RAN) test reliably predicts reading skill,
      it is typically viewed as a diagnostic indicator of risk for reading disability
      (RD). Since most of the work on naming speed has been undertaken within the
      framework of reading research, however, the extent to which poor RAN is
      specifically associated with RD or with learning impairment (LI) in general is
      uncertain. We tested the hypothesis that slow naming speed is specific to RD.
      Participants were 188 children (ages 7 to 11) referred for evaluation of learning
      problems. Receiver operating characteristic (ROC) analysis was used to evaluate
      the utility of the RAN task for classifying children in diagnostic groups. RAN
      was an excellent tool for detecting risk for learning problems in general, but it
      was much less effective at distinguishing LI children with and without RD from
      each other.

PMID- 11992190
TI  - Visual integration difficulties in a 9-year-old girl with Turner syndrome:
      parallel verbal disabilities?
AB  - Turner syndrome (TS) is a genetic disorder in females that arises from the loss
      of X chromosome material. Affected individuals demonstrate a characteristic
      neuropsychological profile of strengths in verbal processing and weaknesses in
      visuospatial processing, consistent with the Nonverbal Learning Disabilities
      syndrome. Previous research has described a wide range of visuospatial deficits
      in TS; however, their verbal abilities are less extensively studied. The present
      paper describes the processing difficulties of a 9-year-old girl with TS who
      demonstrated problems in integrating details of a complex visual display and
      using organizational terms to describe visual scenes or events. Her specific
      cognitive disabilities were thought to underlie some of the social and behavioral
      problems she was currently experiencing. Her pattern of results is consonant with
      the neuropsychological pattern that others have attributed to right hemisphere
      dysfunction and/or white matter abnormality.

PMID- 11992191
TI  - Periventricular leukomalacia (PVL): an identical twin case study illustration of
      white matter dysfunction and nonverbal learning disability (NLD).
AB  - This paper discusses the implications of Periventricular Leukomalacia (PVL)
      lesions for the development of Nonverbal Learning Disabilities (NLD) as
      illustrated through an identical twin case study. PVL lesions were identified in
      an 8-year-old child, but were not detected in his identical twin brother who
      served as a matched comparison. While the nonclinical twin displayed a largely
      unremarkable neuropsychological profile, the clinical twin evidenced a distinct
      pattern of social, intellectual, academic, and neuropsychological test results
      often identified among children with PVL and those with the NLD syndrome. The
      clinical and theoretical implications for this case study are discussed.

PMID- 11992192
TI  - Lack of inhibition: a motivational deficit in children with attention
      deficit/hyperactivity disorder and children with traumatic brain injury.
AB  - Recent research has demonstrated that both brain-injured children and children
      with attention deficit/hyperactivity disorder (ADHD) suffer from response
      inhibition deficits. To investigate whether these deficits can be influenced by
      motivational factors, the stop-signal task was performed with and without reward
      contingencies for successful inhibition. Three groups of children between 8 and
      12 years of age, participated in the study: 31 children with ADHD, 37 with
      traumatic brain injuries (TBI), and 26 normal controls. Results indicated that,
      although all groups showed comparable learning effects, reward contingencies had
      different effects on the groups. Whereas the performance of children with ADHD
      under reward contingencies were brought up to the performance level of normal
      controls, rewards were found less effective at improving response inhibition in
      children with TBI. The results further support a motivational/energetic
      explanation of the inhibitory deficit in children with ADHD, and of a primary
      response inhibition deficit due to structural brain damage in children with TBI.

PMID- 11992193
TI  - Inhibitory deficits in reading disability depend on subtype: guessers but not
      spellers.
AB  - In this study, children with the guessing subtype of dyslexia (who read fast and
      inaccurately) were compared with children with the spelling subtype (who read
      slowly and accurately) on three aspects of executive functioning (EF): response
      inhibition, susceptibility to interference from irrelevant information, and
      planning. It was found that guessers were impaired in their ability to inhibit
      inappropriate responding on all tasks used to assess EF (the stop signal task,
      the Stroop task, and the Tower of London task). This raises the question of
      whether the specific reading disorder of guessers may be linked to the same
      executive deficits which underlie ADHD. In order to unite a fast/inaccurate
      reading style with executive deficiencies, an attempt is made to incorporate the
      concept of executive control into models of lexical activation.

PMID- 11992196
TI  - Psychomotor, executive, and memory function in preclinical Huntington's disease.
AB  - The earliest changes in the development of Huntington's disease (HD) remain
      controversial. Studies of cognitive function in preclinical individuals who have
      the HD mutation have yielded contradictory results. This study compared cognitive
      and motor performance in 51 people with the HD mutation who had no clinical signs
      of HD, 85 at-risk individuals without the HD mutation and 43 individuals in the
      early stages of HD. Whereas highly significant differences were detected between
      the preclinical and early-HD groups, only subtle impairments were present in at
      risk individuals with the HD mutation compared to those with normal HD alleles,
      principally for low-demand psychomotor tasks. Complementing these observations,
      longitudinal investigation showed that performance on psychomotor tasks in people
      with the mutation who were close to clinical onset of HD was intermediate between
      that of individuals many years from onset and those in the early stages of HD,
      suggesting a slowly insidious evolution of deficit. In contrast, memory
      performance showed a more precipitous decline around the time of clinical onset
      of HD. The findings, which suggest that HD patients' functional deficits do not
      evolve uniformly, help to resolve some of the disparities in the literature on
      preclinical HD.

PMID- 11992197
TI  - Self-initiated versus externally cued reaction times in Parkinson's disease.
AB  - It has long been observed that patients with Parkinson's disease (PD) can
      sometimes react and move quickly in response to an external stimulus in a way
      that they cannot when required to initiate the movement themselves. This curious
      phenomenon has sometimes been called 'paradoxical kinesis'. The present study was
      an attempt to demonstrate this phenomenon in patients with PD using an objective
      and quantifiable experimental procedure. A reaction time task was used in which
      participants had to press one of two computer keys, either left or right, to save
      a cartoon person on a computer screen from being run over by a motor car. In one
      condition, trials started after a traffic light appeared on the computer screen
      and then changed from red to green. In a second condition, the participants had
      to first press a third response key which resulted in the traffic light appearing
      on screen and changing from red to green. Participants also received both these
      conditions with the addition of a visual cue, an arrow, which told them in
      advance which direction to respond in (i.e., left or right key) on each trial.
      The purpose of the visual cue was to separate the effects of motor planning from
      motor activation. Healthy controls reacted quickest when they initiated trials
      themselves whereas the PD group were quicker to respond when trials were
      externally generated. Both groups were quicker under the visual cue condition.
      The results are discussed in terms of recent research which has suggested that
      two separate neural systems may be involved in externally generated or
      stereotyped actions and motor responses which require self-generated or
      nonroutine decision making.

PMID- 11992198
TI  - A comparison of three tests to detect feigned amnesia: the effects of feedback
      and the measurement of response latency.
AB  - Three experiments provided validation data for an English language version of the
      Amsterdam Short Term Memory Test (ASTM test) developed to detect feigned memory
      impairment. Using a simulation design, the ASTM test compared favourably with the
      Test of Memory Malingering (TOMM) and appeared better than a newly-devised Digit
      Recognition Test (DRT). Feedback on the correctness of responses had no
      significant effect on performance but notable trends were apparent. Simulators
      were significantly slower than controls on computerised versions of the ASTM test
      and the TOMM. Convergent findings indicate that the English language version of
      the ASTM test may be useful in detecting malingering.

PMID- 11992199
TI  - A preliminary psychometric analysis of a computer-assisted administration of the
      Telephone Interview of Cognitive Status-modified.
AB  - Most screening tests of cognitive functioning require face to face administration
      by trained examiners. This limits their utility in epidemiology and in primary
      care settings. Further, existing screening tests have not been developed using
      established psychometric principles. We adapted the Telephone Interview of
      Cognitive Status-modified (TICSm) for administration as a computer-assisted
      telephone interview (CATI). We screened 3,681 elderly women with the CATI version
      of the TICSm, using lay staff as part of a longitudinal study. A preliminary
      analysis of the psychometric properties of the TICSm indicated good internal
      consistency. Test-retest reliability is needed to confirm reliability. Further
      work remains to adequately judge the validity of the TICSm including comparisons
      with well-standardized tests and assessment of its predictive properties in
      identifying dementia. However, the CATI version of the TICSm appears to have
      potential as a cost-effective means of testing cognitive performance.

PMID- 11992200
TI  - Dissociated conditional-associative learning in anorexia nervosa.
AB  - This study assessed the acquisition of conditional-associations using neutral and
      individually threatening nouns in 16 females with anorexia nervosa (AN), 16
      females with bulimia nervosa (BN) and 16 normal controls (NC). Groups did not
      differ in terms of age, sex, handedness, depression, intelligence, verbal memory
      and verbal fluency measures. Furthermore, patients and controls were widely
      comparable on any test assessing neuropsychological functioning. In the
      conditional-associative learning (CAL) task, anorexic patients displayed an
      impaired performance with neutral material but not with individually threatening
      material. Such a deficit was not evident in bulimics or in normal controls. Only
      anorexics showed a dissociation in the CAL of material with different emotional
      valence. These findings support the assumptions from functional neuroimaging
      investigations in AN and justify the assignment of this disorder to the obsessive
      compulsive spectrum disorders.

PMID- 11992201
TI  - A longitudinal study of the relationship between financial compensation and
      symptoms after treated mild traumatic brain injury.
AB  - Demographic, injury-related, and symptom variables at intake, 3 months, and 12
      months postinjury were compared between 50 treated adults with mild traumatic
      brain injury (MTBI) who were not seeking or receiving financial compensation at
      any time and 18 who were at each time. Compensation seekers/receivers reported
      symptom incidence and severity as approximately 1 SD higher at each time. The
      level of difference between the groups did not significantly differ across time.
      No demographic variables distinguished the groups. No injury-related variable
      other than more immediate postinjury prescription medication use was predictive
      of the greater symptom complaints for the patients seeking or receiving
      compensation. However, this medication effect did not explain away the
      compensation effect when medication use was co-varied in an analysis. Our study
      appears to be the first to examine the relationship between financial
      compensation and symptom report in an MTBI sample specifically treated for their
      condition. Our results indicate that even highly patient-rated treatment is not
      adequate to wash out the strong relationship between financial compensation
      status and symptom report after MTBI.

PMID- 11992202
TI  - Latent structure of the Children's Category Test after pediatric traumatic head
      injury.
AB  - The performance of 100 9-16-year-old children with traumatic head injury (THI) on
      the Children's Category Test (CCT-2; Boll, 1993) was examined to determine the
      underlying factor structure. Exploratory principal factor analysis with oblique
      rotation identified a two-factor solution. Factor 1 was composed primarily of
      subtests IV, V, and VI, whereas Factor 2 was defined primarily by subtests III
      and VI. Age and Full Scale IQ, as measured by the Wechsler Intellectual Scale for
      Children-Third Edition (WISC-III; Wechsler, 1991), were significantly related to
      both factors. Factor 1, but not Factor 2, demonstrated clear sensitivity to
      severity of THI. It is concluded that interpretation of the CCT-2 with children
      who have sustained a THI should consider the multifactorial nature of the
      instrument, and that exclusive reliance on the summary total error score may
      impede diagnostic accuracy.

PMID- 11992203
TI  - Facial identity and facial emotions: speed, accuracy, and processing strategies
      in children and adults.
AB  - As yet, nearly all studies in face and facial affect recognition typically
      provide only data on the accuracy of processing, invariably also in the absence
      of reference data on abstract information processing. In this study, accuracy and
      speed of abstract visuo-spatial processing, face recognition, and facial emotion
      recognition were investigated in normal school children (7-10 years) and adults
      (25+/-4 years). In the age range of 7-10 years, accuracy of facial processing
      hardly increased, while speed did substantially increase with age. Adults,
      however, were substantially more accurate and faster than children. Differences
      between facial and abstract information processing were related to type of
      processing strategy, that is, configural or holistic processing versus featural
      or piecemeal processing. Improvement in task performance with age is discussed in
      terms of an enhanced efficiency of the configural organization of facial
      knowledge (facial information processing tasks), together with a further increase
      in processing capacity (all tasks). The differential developmental course of
      speed and accuracy levels indicates that speed is a more sensitive measure when
      children get older. Moreover, it also suggests that speed of performance, in
      addition to accuracy, might be successfully used in the assessment of clinical
      deficits, as has recently been demonstrated in children with autistic disorders
      of social contact.

PMID- 11992204
TI  - Mayo's Older Americans Normative Studies: expanded AVLT Recognition Trial norms
      for ages 57 to 98.
AB  - This paper expands upon previously published Mayo's Older Americans Normative
      Studies (MOANS) Auditory Verbal Learning Test (AVLT) norms by presenting age and
      gender specific data for Recognition Trial accuracy (recognition 'hits' corrected
      for false positive errors) in a total of 836 subjects (the original sample,
      augmented by an additional 311 subjects). Observations are offered concerning
      clinical implications of AVLT Recognition Trial performance. Gender differences
      in recognition memory are discussed.

PMID- 11992205
TI  - Executive functions in the evaluation of accident risk of older drivers.
AB  - The main objective of these studies was to analyse the difference in driving
      attitude and aptitude, between two groups of elderly male drivers (65 years or
      more), one being accident-free and the second having three accidents or more in
      the last 5 years. The first study compared the driving habits of 90 older
      accident-free drivers with 90 drivers having a history of accidents. The second
      study, on a subgroup of 60 of the original 180 subjects (30 accident-free and 30
      having accidents), compared cognitive function, with particular emphasis on
      executive functions as measured by neuropsychological tests, and attitude and
      self-reported driving behaviour. The results show that elderly drivers having a
      history of accidents, compared to the control group: (1) have poorer performance
      on the four cognitive measurements of executive functions; (2) report to have
      more prudent behaviour on the road (e.g., reducing their speed); and (3) have the
      intention to adopt less risky driving behaviour. This study suggests that a
      subgroup of the older driver population has cognitive problems and driving
      disabilities that cannot be compensated by apparently more careful behaviour on
      the road. The results confirm the importance of proper assessment of cognitive
      processes and underscore the potential of measuring executive functions for the
      evaluation of driving competence of elderly persons.

PMID- 11992206
TI  - Learning, retention and generalization of a mirror tracing skill in Alzheimer's
      disease.
AB  - The present study examined the ability of 12 patients with probable Alzheimer's
      disease (AD) and 12 age- and education-matched normal control (NC) subjects to
      learn and retain the visuomotor skills necessary to efficiently trace a pattern
      (e.g., a 4- or 6-pointed star) seen only in mirror-reversed view. Those AD (N=6)
      and NC (N=7) subjects who were able to initially perform the basic mirror tracing
      task did not differ significantly in initial level of performance, learning over
      trials, retention of the skill over a 30-min delay interval, and generalization
      of the skill to a new figure or to the opposite direction of tracing. The AD
      patients who were unable to initially perform the mirror tracing task were
      significantly worse than those who could perform the task on several
      neuropsychological measures sensitive to deficits in problem solving and
      executive functions, but not on tests of global cognitive decline, memory,
      language, or visuoperceptual functioning. These results indicate that acquisition
      and retention of a complex visuomotor skill can proceed normally in the early
      stages of AD in those individuals who can initially perform the basic task, and
      that inability to perform the basic task may be related to the frontal lobe
      dysfunction that is often prominent in the disorder.

PMID- 11992207
TI  - Utility of olfactory identification test for diagnosing Chinese patients with
      Alzheimer's disease.
AB  - The present study examined the utility of two tests, the olfactory identification
      test and the olfactory threshold test, in detecting dementia of the Alzheimer's
      type in Chinese patients in Hong Kong. The olfactory identification test
      developed by Murphy, Anderson, and Markinson (1994) was utilized with some
      modifications of odor stimuli suitable for the Chinese culture. Results showed
      that patients with Alzheimer's disease (AD) identified significantly fewer odors
      and had significantly higher olfactory threshold than their age- and education
      matched normal control subjects. With the cut-off point of 5 identified odors
      (out of 6), the olfactory identification test yielded a sensitivity of 83% in
      discriminating AD patients from normal controls which was consistent with that
      reported by Morgan, Nordin, and Murphy (1995). Thus, the present results
      suggested that the olfactory identification test could be applied cross
      culturally for identifying patients with dementia of the Alzheimer's type.

PMID- 11992208
TI  - Obsessive-compulsive disorder (OCD) patients are impaired in remembering temporal
      order and in judging their own performance.
AB  - Obsessive-compulsive disorder (OCD) has been related to frontostriatal
      dysfunction, but some inconsistencies between studies and a relative paucity of
      neuropsychological research still characterizes the study of OCD. We compared 28
      patients with OCD and matched healthy controls on two neuropsychological tests
      sensitive to frontal dysfunction: temporal ordering and a "feeling-of-doing"
      (FOD) judgment about ordering. The OCD group performed significantly worse than
      controls in the temporal ordering task despite showing normal recognition memory.
      Patients were also impaired in "feeling-of-doing" judgments suggesting they have
      a lack of self-awareness of their performance. Thus, the results of the current
      study reinforces previous research that indicates that OCD patients fail on tasks
      that require adequate functioning of the frontal-striatal pathways.

PMID- 11992209
TI  - Mood and anxiety disorders following pediatric traumatic brain injury: a
      prospective study.
AB  - Studies utilizing standardized instruments for assessing mood and/or anxiety
      disorders following pediatric traumatic brain injury have seldom been reported in
      the literature. Previous reports have largely focused on cognitive impairment,
      behavioral dysfunction, or adaptive functioning, and have typically relied on
      parental informants. In this study, children hospitalized for mild (N = 42) and
      moderate/severe (N = 19) brain injury were assessed 6-months postinjury using the
      Anxiety disorders Module A and the Mood disorders Module C of the Diagnostic
      Interview Schedule for Children - IV Revision (DISC-IV). The data collected for
      the brain injury groups were compared to an orthopedic control group (N = 35).
      The relationship between a new onset mood and/or anxiety disorder (NOD) and
      injury severity indices was examined. Sequential logistical regression was also
      utilized to examine the impact of a brain injury, demographic variables,
      preinjury psychiatric disturbance, development disorders, litigation status and
      postinjury environmental stress on emotional outcome. Results indicated a
      relationship between brain injury and NOD. Multivariate analysis demonstrated
      that postinjury level of stress and severity of brain injury were the most robust
      predictors of NOD, accounting for 23% of the variance in the model. These results
      support the premise that the development of a mood and/or anxiety disorder
      following pediatric head injury is mediated by multiple determinants. The
      findings suggest that early psychosocial assessment and interventions aimed at
      increasing a child's coping may attenuate the emotional consequences of pediatric
      brain injury.

PMID- 11992210
TI  - Academic and cognitive abilities in children of parents with bipolar disorder: a
      test of the nonverbal learning disability model.
AB  - It has been hypothesized that children who are at genetic risk to develop bipolar
      disorder demonstrate deficiencies consistent with the syndrome of nonverbal
      learning disabilities (NLD); however, this hypothesis has never been tested
      directly. In the present study, a group of at-risk children (AR group; N = 28)
      was compared to a demographically matched control group of children of healthy
      parents (HC group; N = 24) for evidence of a constellation of features associated
      with NLD. Some characteristic features of NLD were evident, including significant
      Verbal IQ (VIQ) > Performance IQ (PIQ) discrepancies and psychomotor deficits.
      However, academic deficiencies in mechanical arithmetic relative to reading and
      spelling abilities were not demonstrated. These findings replicate and extend the
      current literature on the cognitive functioning of children of parents with
      Bipolar disorder (BPD). The results, however, do not support the presence of NLD
      in these children.

PMID- 11992211
TI  - Performance of older adults on tests of cognitive estimation.
AB  - This study provides performance data for older adults on two existing tests of
      cognitive estimation ability (Cognitive Estimation Test [CET] and Temporal
      Judgement Test [TJT]) and a novel set of estimation questions (n-EQ) that make
      reference to familiar, everyday objects. It explores the relations between each
      of the three tests of estimation and verbal intelligence. The sample comprises
      101 adults aged 55 years and over. Neither n-EQ nor TJT scores were associated
      with verbal IQ, but scores on the more established CET were. As well as providing
      performance data for older adults, this study confirms the limitations of
      existing measures of cognitive estimation. It is proposed that the novel
      questions devised for this study show promise as an assessment tool, and warrant
      further validation.

PMID- 11992212
TI  - Bereavement-related cognitive impairment in an oldest-old community-dwelling
      Brazilian sample.
AB  - As it is already known that depression can cause a demonstrable impact on
      cognition in elderly subjects, the objective of this study was to determine
      whether also the mourning process is associated with any cognitive impairment in
      this age range. A random and representative sample (a sample with 77
      subjects/total county population of oldest-old with 219 subjects = 35%) aged 80
      years or more was selected from the county of Veranopolis in the Brazilian rural
      southern region. Of this group, the cognitive function of subjects without grief
      and of subjects with the presence of grief were compared. Five neuropsychological
      tests (the Buschke-Fuld Selective Reminding Test, the word-list from the CERAD
      battery, the Verbal Fluency Test, and two subtests of the Wechsler memory scale),
      the Mini-Mental State Examination (MMSE) and two self-perceived memory impairment
      questionnaires were used. Presence of depressive symptomatology was identified by
      the Yesavage Geriatric Depression Scale (GDS). The prevalence rates of some
      psychiatric diagnoses (syndromic general anxiety disorder, major and minor
      depression) were compared between the bereaved group and the control group. There
      was not a statistically significant difference between the scores of controls and
      subjects with grief in the GDS. The frequency of affective disorders in both
      groups did not differ. However, the recently bereaved elderly subjects presented
      a mild cognitive impairment when evaluated with the MMSE, with the digit span
      test and with Word-list neuropsychological memory test. Likewise these bereaved
      octogenarian subjects presented more frequently a diagnosis of 'aging-associated
      cognitive decline' when compared with non-bereaved oldest-old. These results
      suggest that the normal sadness and/or the chronic stress of the grieving
      process, even without the presence of an identifiable syndromal-level depression,
      are associated with memory and cognitive differences among the bereaved oldest
      old. Cause-effect relationships, however, cannot be established from this cross
      sectional correlational study: Grief may influence cognitive functioning in the
      elderly, but mildly cognitively compromised elderly persons may be more likely to
      experience strong grief reactions after loss.

PMID- 11992213
TI  - More evidence for the role of the central executive in retrieving arithmetic
      facts - a case study of severe developmental dyscalculia.
AB  - It has been shown repeatedly that simple mental calculation depends not only on
      long-term memory (LTM) representations but also on working memory (WM) resources.
      The study describes the performance of an adolescent, M.O., exhibiting severe
      developmental dyscalculia, but literacy problems as well. Despite having
      relatively preserved procedural skills, M.O. exhibited outstanding difficulties
      in retrieving arithmetic facts which are most pronounced on multiplication and
      division problems. Interestingly, his performance on non-numerical memory tests
      was within average (independent of modality), while his attention span was just
      below average. Testing the different components of WM, the results emphasize the
      major role of the central executive in solving simple mental calculations.

PMID- 11992214
TI  - Familial association of neuropsychological traits in patients with generalized
      and partial seizure disorders.
AB  - To investigate familial effects of neuropsychological deficits associated with
      seizure disorders, we studied 65 families, in which 1 member had epilepsy. The
      disorders included childhood absence epilepsy (CAE), juvenile myoclonic epilepsy
      (JME) and temporal lobe epilepsy (TLE). Age-appropriate tests were administered
      to assess sustained attention, encoding and verbal memory, executive and focused
      attention and attentional flexibility/impulsivity. CAE probands attained lower
      scores than other probands in visual sustained attention and the ability to focus
      on and execute a visual-motor task. Scores of the unaffected relatives tended to
      fall between those of the probands and the controls. JME relatives had lower
      scores than other relatives in tests of visual and auditory sustained attention
      and attentional flexibility, and showed greater variability in response time.
      Behavioral information of this type may aid in the specification and
      differentiation of genetic linkages in affected families.

PMID- 11992215
TI  - Pseudoword and real word memory in unilateral temporal lobe epilepsy.
AB  - Recognition memory for pronounceable pseudowords (PWs), real words, and degraded
      photographs of unfamiliar faces, was examined in 45 patients with unilateral
      temporal lobe epilepsy (TLE), before and after Anterior Temporal Lobectomy, to
      test predictions from two accounts of hemispheric differences in memory
      functioning: (1) The 'material-specific' account predicts that left TLE (LTLE)
      patients would be impaired in memory for both familiar (real words) and
      unfamiliar (PWs) verbal stimuli, while memory for novel complex visual stimuli
      (unfamiliar faces) would be impaired in right TLE (RTLE) patients. (2) The
      'familiarity' account predicts that memory for familiar stimuli (such as words)
      will be impaired in LTLE patients, while memory for both linguistic and
      nonlinguistic unfamiliar stimuli should be disrupted in RTLE patients. Results
      were consistent with the 'material-specific' hypothesis suggesting that both
      familiar and unfamiliar linguistic stimuli are processed for memory in the left
      medial temporal lobe (MTL), whereas unfamiliar nonverbal stimuli are processed
      for memory in the right MTL.

PMID- 11992216
TI  - Neurophysiological and clinical aspects of glucocorticoids and memory: a review.
AB  - Neuropsychologists are increasingly involved in the assessment and treatment of
      individuals with glucocorticoid (GC) dysfunction. This review examines the
      clinical and neurophysiological changes associated with alterations in GC levels,
      with specific emphasis on changes in hippocampal plasticity and memory
      impairments. Hypothalamic-pituitary-adrenal (HPA) axis regulation of GC
      production and GC effects at hippocampal receptors are examined. GC-related
      changes in memory and hippocampal plasticity are considered in a wide array of
      populations, including animals, healthy adults, patients receiving exogenous GC
      treatments, and patients with neuropsychiatric disorders resulting in GC
      dysregulation. Hypotheses regarding GC-related memory changes are considered,
      with emphasis on hippocampal neurotoxicity and changes in excitatory amino acids,
      glucose metabolism and neurotrophic factors. These hypotheses are examined, with
      special attention given to inconsistencies and contradictions within this body of
      research. Finally, implications for neuropsychological evaluation and future
      research are presented.

PMID- 11992217
TI  - Effects of task structure on category priming in patients with Parkinson's
      disease and in healthy individuals.
AB  - Lexical decision tasks have been used to study both shifts of attention and
      semantic processing in Parkinson's Disease (PD). Whereas other laboratories have
      reported normal levels of semantic priming among PD patients, our laboratory has
      reported abnormally large levels. In this study, two experiments were performed
      to determine the influence of task structure on the extent of semantic priming
      during lexical decision-making and pronunciation tasks among PD patients and
      neurologically healthy controls. In Experiment 1, the effect of Prime Dominance
      (the ratio of category to neutral trials) on lexical decision-making was studied.
      Although equal numbers of word and nonword trials were presented, half of the PD
      patients and controls were studied under Category Prime Dominance (category :
      neutral prime ratio of 2:1) and half were studied under Neutral Prime Dominance
      (category : neutral prime ratio of 1:2). In Experiment 2, PD and control
      participants were studied on lexical decision-making and pronunciation tasks
      where twice as many words as nonword trials were presented, consistent with other
      studies from our laboratory. In Experiment 1, we found no group differences in
      the magnitude of priming and no effect of Prime Dominance. Moreover, the findings
      were similar in pattern and magnitude to results published by Neely (1977). In
      Experiment 2, we observed larger priming effects among PD patients than among
      controls, but only on the lexical decision (LD) task. These results support the
      hypothesis that abnormally large category-priming effects appear in LD studies of
      PD patients when the number of word trials exceeds the number of nonword trials.
      Furthermore, increased lexical priming in PD appears to be due to processes
      operating during the decision-making period that follows presentation of the
      lexical target.

PMID- 11992218
TI  - Comparability of total score performance on the Rey-Osterrieth Complex Figure and
      a modified Taylor Complex Figure.
AB  - One of the most commonly used neuropsychological measures of visuo-spatial
      abilities is the Rey-Osterrieth Complex Figure (ROCF) Test. Previous research has
      reliably shown that its companion figure, the Taylor Complex Figure, is not a
      comparable measure of visuo-spatial memory. The aims of the three studies
      presented here are to (a) introduce a modified version of the Taylor Figure
      (MTCF), and (b) examine the comparability of the ROCF and the MTCF using two
      different administration procedures. The first two studies used a between
      subjects design in which half of the study participants received the ROCF and
      half received the MTCF. In Study 1, an incidental procedure was used in which
      participants were asked to first copy a figure and then reproduce it from memory
      without prior warning. In Study 2, an intentional procedure was used in which
      participants were first asked to observe the figures for the express purpose of
      reproducing them from memory followed by delay and copy trials. In Study 3, a
      within-subjects design using counterbalancing and an intentional procedure was
      used to examine the comparability of the two figures when administered to the
      same participants as in a true test-retest situation. Overall, the studies
      demonstrated that learning, memory, and copy score performance on the MTCF was
      comparable to that on the ROCF.

PMID- 11992219
TI  - From the Binet-Simon to the Wechsler-Bellevue: tracing the history of
      intelligence testing.
AB  - The history of David Wechsler's intelligence scales is reviewed by tracing the
      origins of the subtests in the 1939 Wechsler-Bellevue Intelligence Scale. The
      subtests originated from tests developed between 1880 and World War I, and was
      based on approaches to mental testing including anthropometrics, association
      psychology, the Binet-Simon scales, language-free performance testing of
      immigrants and school children, and group testing of military recruits.
      Wechsler's subtest selection can be understood partly from his clinical
      experiences during World War I. The structure of the Wechsler-Bellevue Scale,
      which introduced major innovations in intelligence testing, has remained almost
      unchanged through later revisions.

PMID- 11992221
TI  - Association of postdoctoral programs in clinical neuropsychology: update and new
      directions.
AB  - This paper provides an update on the Association of Postdoctoral Programs in
      Clinical Neuropsychology (APPCN), which was formed in 1992. The paper summarizes
      the historical background of APPCN, reports on contemporary influences on APPCN
      and its role in postdoctoral education and training in neuropsychology, and
      provides an update on APPCN's most recent initiatives. The paper includes a list
      of current members in APPCN and explains how other postdoctoral residency
      programs in clinical neuropsychology may apply for membership.

PMID- 11992222
TI  - Are normative data from the 64-card version of the WCST comparable to the full
      WCST?
AB  - A retrospective study of Wisconsin Card Sorting Test (WCST) protocols was
      undertaken to determine the equivalence of the full WCST (Heaton, Chelune,
      Talley, Kay, & Curtiss, 1993) with the single-deck version of the WCST. Census
      matched and demographically adjusted standardized scores for the full WCST were
      compared to the single deck WCST (WCST-64) with 332 clinical protocols using two
      methods. The comparisons were made using (1) standard scores derived from the new
      WCST-64 norms (Kongs, Thompson, Iverson, & Heaton, 2000) and from (2) WCST-64
      percent scores standardized with the norms intended for the full WCST. The
      results revealed adequate correlations and accuracy scores for both census-based
      norms, although WCST-64 scores adjusted for demographic information were not
      comparable to full WCST scores. Furthermore, the number of cases in which
      estimated scores performed within an acceptable range of actual full-version WCST
      scores fell below acceptable ranges. Clinicians are encouraged to use data from
      the WCST-64 with caution.

PMID- 11992223
TI  - Neuropsychological characteristics of adults with ADHD: a comprehensive review of
      initial studies.
AB  - The role of neuropsychological evaluation in the diagnosis of adults with
      Attention-Deficit/Hyperactivity Disorder (ADHD) is a growing area of research and
      clinical interest. Our review of the literature indicates that adults with ADHD
      demonstrate subtle impairments on select measures of attention and executive
      functions, auditory-verbal list learning, and complex information processing
      speed relative to normal controls. The validity of these findings is nonetheless
      hampered by several limitations, including methodological and sample variability,
      a restricted range of interpretive techniques, and uncertain discriminant
      validity. Recommendations are offered to advance the cognitive and
      neurobehavioral understanding of this disorder and to enhance the utility of
      neuropsychological methods for diagnosis and management of adults with ADHD.

PMID- 11992224
TI  - Diagnostic utility of letter fluency, category fluency, and fluency difference
      scores in Alzheimer's disease.
AB  - Word generation tasks, specifically letter fluency and category fluency, are a
      standard part of most test protocols used by clinical neuropsychologists to
      measure aspects of language and executive retrieval functions. Given the reliance
      on these measures as clinical tools, it is important to understand the diagnostic
      implications of patients' performances. In Alzheimer's disease (AD), category
      fluency has generally been found to be disproportionately impaired, whereas
      letter fluency is usually more mildly impaired. It has been proposed that this
      performance pattern occurs because access to temporal-lobe semantic stores is
      necessary for category fluency but not letter fluency. In this study, the
      diagnostic utility of category fluency, letter fluency, and difference scores
      (letter fluency minus category fluency) in AD were examined. Forty AD patients
      and 221 normal control subjects took category fluency and letter fluency tests.
      Traditional t-test comparisons revealed that the groups differed significantly on
      the two test tasks and in terms of mean difference scores. However, using
      sensitivity and specificity to calculate predictive values, only category fluency
      and letter fluency (but not difference scores) were useful in predicting AD in
      individuals. Furthermore, category fluency was superior to letter fluency in this
      regard. Likelihood ratio tables are provided for use in calculating the odds of
      AD for specific category fluency and letter fluency scores generated by
      individual patients.

PMID- 11992225
TI  - Neuropsychological tests in the elderly: methods and sample characteristics of a
      GRECC study.
AB  - This report describes the methods and sample characteristics of a
      neuropsychological study of the elderly conducted by the Geriatric Research,
      Education and Clinical Center of the Department of Veterans Affairs Medical
      Center in Minneapolis, Minnesota. The goal of the study was to provide normative
      data, internal consistency and 1-year reliability estimates, and validated
      methods of estimating expected performance level. Thirty-one cognitive measures
      and a demographic questionnaire were administered to an age-, education-, and
      gender-stratified sample ( N = 349) and a validation sample (N = 70). After 1
      year, 104 of the participants were retested. Relative to published, nationally
      based normative data, the stratified sample showed performance levels that ranged
      from average to high average across the five tests examined.

PMID- 11992226
TI  - Facial recognition test in the elderly: norms, reliability and premorbid
      estimation.
AB  - The Facial Recognition Test (Benton, Hamsher, Varney, & Spreen, 1983; Benton,
      Sivan, Hamsher, Varney, & Spreen, 1994) was examined in an age-, education- and
      gender-stratified sample of 346 healthy older adults. Internal consistency
      reliability estimates were.72 for the Long Form (FRLF),.53 for the Short Form,
      and.69 for a new short form. Mean FRLF scores did not change over a 1-year
      interval (p >.5), and the stability estimate was.71 (n = 100). The first of the
      methods below yielded the highest correlation between estimated and obtained FRLF
      scores in cross-validation (n = 67): (1) multiple regression based on oral
      reading and demographics, (2) multiple regression based on age, education and
      gender, and (3) mean scores by age group.

PMID- 11992227
TI  - Practice effects on the WAIS-III across 3- and 6-month intervals.
AB  - Fifty-one participants (age M = 24.6; education M = 14.4 years) were administered
      the Wechsler Adult Intelligence Scale - Third Edition (WAIS-III) at baseline and
      at an interval of either 3 or 6 months later. Full Scale IQ (FSIQ), Verbal IQ
      (VIQ), Performance IQ (PIQ), Verbal Comprehension Index (VCI), Perceptual
      Organization Index (POI), and Processing Speed Index (PSI) scores improved
      significantly across time, whereas no significant change occurred on the Working
      Memory Index. Specifically, test scores increased approximately 3, 11, 6, 4, 8,
      and 7 points, respectively on the VIQ, PIQ, FSIQ, VCI, POI, and PSI for both
      groups. Notably, the degree of improvement was similar regardless of whether the
      inter-test interval was 3 or 6 months. These findings suggest that prior exposure
      to the WAIS-III yields considerable increases in test scores. Reliable change
      indices indicated that large confidence intervals might be expected. As such,
      users of the WAIS-III should interpret reevaluations across these intervals
      cautiously.

PMID- 11992228
TI  - Testing prospective memory: does the value of a borrowed item help people
      remember to get it back?
AB  - The relationship between the value of an item borrowed from a patient for a
      prospective memory task and the number of cues required by the patient for
      requesting its return was analyzed in 63 consecutive patients referred for
      clinical neuropsychological evaluation. The correlation was negligible (rho = 
      .001). Number of cues needed was better predicted by score on the Mini-Mental
      State Exam (r = -.541, p <.001) than by subject's age, sex, or education, or the
      value of the item taken.

PMID- 11992229
TI  - Stroop test in Spanish: children's norms.
AB  - Three hundred and forty-nine first to sixth graders (ages 6 years and 6 months to
      12 years and 11 months) from two Mexican schools (one private and one public)
      were administered the Comalli-Kaplan version of the Stroop test in Spanish, as
      part of a larger protocol. Findings are discussed in the context of current
      interpretations of the Stroop test, considered a measure of inhibition. No gender
      differences were observed. Parental education was a statistically significant but
      unimportant predictor of performance. Developmental norms are provided, together
      with analyses of the amount of interference encountered (in time and errors) for
      each age.

PMID- 11992230
TI  - Error analysis of the nine-word California Verbal Learning Test (CVLT-9) among
      older adults with and without dementia.
AB  - The nine-word California Verbal Learning Test (CVLT-9; Libon et al., 1996; Spreen
      & Strauss, 1998) is a verbal list learning task used to assess declarative memory
      impairment among dementia patients. The present study sought to investigate the
      neuro-cognitive mechanisms that underlie the production of intrusions and
      perseverations on the list A, free recall learning trials, and the false positive
      responses made on the delayed recognition condition. Patients with probable
      Alzheimer's disease (AD), Ischaemic Vascular Dementia associated with
      periventricular and deep white matter changes (IVD), and individuals without
      dementia (NC) were studied. Between-group analyses showed that AD participants
      produced more initial intrusion errors, and perseverated on those same intrusion
      errors across list A learning trials than IVD or NC participants. Also, as
      participants with dementia produced initial free recall intrusion errors, the
      semantic organization of their responses on the 'animal' word list generation
      task declined (Giovannetti-Carew, Lamar, Cloud, Grossman, & Libon, 1997). On the
      delayed recognition test condition, within-group analyses revealed that the IVD
      group endorsed more list B interference foils, than other errors. AD participants
      endorsed semantically related foils and list B interference foils. In addition,
      as participants with dementia endorsed more list B interference foils, more
      perseverations were produced on the Graphical Sequence Test - Dementia Version
      (Lamar et al., 1997). These results were interpreted within the context of the
      semantic knowledge, and executive functions deficits that typify AD and IVD,
      respectively.

PMID- 11992231
TI  - Suspect cognitive symptoms in a 9-year-old child: malingering by proxy?
AB  - Even though the veracity of children's claim of psychiatric symptoms has received
      increased attention in recent years, identification of noncredible
      neuropsychological symptoms in children has been virtually overlooked in clinical
      practice and research. A case is presented of a 9-year-old child involved in
      litigation regarding a head injury sustained when he was struck by a car.
      Neuropsychological evaluation revealed evidence of feigned cognitive symptoms;
      the child displayed noncredible performance on several specialized tests designed
      to discreetly assess effort and an atypical pattern of responses on standard
      cognitive measures, as well as discrepancies between neuropsychological scores
      and tests administered in school and the rehab setting. Results demonstrate that
      children as young as 9 years of age are capable of feigning cognitive impairment,
      which highlights the need for routine evaluation of effort, irrespective of the
      age of the patient.

PMID- 11992232
TI  - Ethical considerations for peer review in forensic neuropsychology.
AB  - The role of an expert is to assist the trier of fact in weighing evidence and
      reaching conclusions. Critical evaluation of opposing experts is an integral part
      of this process. In more recent times, cross-examination has given way to
      critical evaluation of opposing experts outside of the courtroom, a tactic we
      refer to as peer review in this paper. Though neuropsychologists frequently
      review the work of their colleagues, we are concerned here primarily with
      commentary that is at best misleading, and occasionally malicious, unethical, and
      unprofessional. Despite a growing trend to use experts as peer reviewers in the
      medicolegal arena, expectations concerning ethical and professional conduct of
      neuropsychologists have been absent. Enforcement of appropriate conduct is
      further complicated by the ambiguity of existing ethical standards and state
      statutes, and their limited applicability to all neuropsychologists who provide
      forensic services. This article provides an overview of ethical and professional
      issues pertaining to forensic peer review and concludes with recommendations for
      appropriate professional conduct.

PMID- 11992235
TI  - Response of von Willebrand factor parameters to desmopressin in patients with
      type 1 and type 2 congenital von Willebrand disease: diagnostic and therapeutic
      implications.
AB  - In the present study, we prospectively evaluated the contribution of the von
      Willebrand factor collagen-binding activity (vWF:CBA) assay, vWF multimeric
      analysis, and the response to intravenous desmopressin (DDAVP) to correctly
      diagnose and classify congenital von Willebrand disease (CvWD) in 24 probands
      with mild to moderate type 1 vWD, 6 probands with severe CvWD type 1, and 12
      probands with type 2 CvWD. CvWD type 1 of mild to moderate severity is featured
      by proportionally decreased levels of vWF antigen (vWF:Ag), vWF ristocetin
      cofactor activity (vWF:RCof), and vWF:CBA between 0.20 and 0.60 u/mL and a normal
      response to DDAVP of factor (F) VIIIc and all vWF parameters. Severe type 1 CvWD
      with vWF parameters below 0.10 or 0.20 u/mL is associated with a decreased
      response to DDAVP of all vWF parameters, indicating a defective synthesis or
      secretion vWF by endothelial cells, or both. CvWD 2M may present as severe type 1
      CvWD, as type 1 "platelet-discordant" CvWD, or with the combination of a
      discrepant vWF:RCof/Ag ratio and the presence of all vWF multimers. Ristocetin
      induced platelet aggregation (RIPA) is normal in type 1 CvWD. CvWD 2M is
      typically featured by decreased RIPA, normal or near normal vWF multimers, and no
      or only a poor response to DDAVP of vWF:RCof as compared with a fairly good
      response to DDAVP of vWF:Ag and vWF:CBA. CvWD Vicenza is characterized by
      unusually large vWF multimers and very low levels of FVIIIc, vWF:Ag, and
      vWF:RCof. CvWD Vicenza differs from CvWD 2M because the vWF:RCof/Ag ratios are
      completely normal before and after DDAVP; the response to DDAVP is equally good
      for FVIIIc, vWF:Ag, vWF:RCof, and vWF:CBA and is followed by very short half-life
      times for FVIIIc and all vWF parameters. Pertinent findings in type 2A and 2B
      CvWD included prolonged Ivy bleeding time (BT), low vWF:RCof/Ag and vWF:CBA
      ratios, absence of the high vWF multimers, and, depending on the severity of the
      absence of intermediate vWF multimers, pronounced increase of low vWF multimers
      and vWF degradation products because of increased proteolysis of the high and
      intermediate vWF multimers. RIPA is normal in CvWD 2A and increased in CvWD 2B.
      The response to DDAVP in CvWD 2A is normal for FVIIIc and vWF:Ag but is transient
      with partial correction and short half-life times of vWF:CBA and vWF:RCof. DDAVP
      does not correct BT and multimeric patterns in CvWD type 2B, despite significant
      increase of vWF parameters. CvWD types 2C, 2D, and 2E are featured by very low
      functional vWF parameters, the presence of typically abnormal vWF multimers, a
      very poor response of vWF:CBA, a decreased response of vWF:RCof, and a fairly
      good response of vWF:Ag to DDAVP with no correction of prolonged Ivy BT and no
      correction of the vWF multimeric pattern as the consequence of a multimerization
      or dimerization defect of the vWF molecules. CvWD type 2N usually presents with
      much lower levels for FVIIIc as compared with vWF, normal Ivy BT, and normal vWF
      multimeric pattern. The response to DDAVP is normal for all vWF parameters but is
      decreased for FVIIIc with shortened half-life times.

PMID- 11992236
TI  - The role of von Willebrand factor in platelet function.
AB  - von Willebrand factor (vWF) has essential functions in the very first stage of
      hemostasis. At the site of vascular damage vWF binds immediately to exposed
      collagens, thereby facilitating the adhesion of platelets. After a first layer of
      platelets has been formed, vWF is also crucial as a link between platelets in the
      forming thrombus. In this article, the current knowledge on the role of vWF in
      primary hemostasis is reviewed.

PMID- 11992237
TI  - Comparison of two von Willebrand factor collagen-binding assays with different
      binding affinities for low, medium, and high multimers of von Willebrand factor.
AB  - The use of von Willebrand factor collagen-binding assay (vWF:CBA) as an
      alternative method for the quantification of the physiological activity of vWF in
      plasma from patients with von Willebrand disease (vWD) and in blood clotting
      factor (F) VIII concentrates (FVIII/vWF concentrates) for the therapy of vWD is
      currently being discussed. We compared two vWF:CBAs that are distinctive with
      regard to the type and structure of collagen and the coating principle used.
      After analyzing samples of a plasma pool from normal donors, we received results
      that were in very good compliance with both methods. However, significantly
      different results (p < or =0.005) were obtained when FVIII/vWF concentrates were
      tested. In an attempt to elucidate these discrepancies, vWF multimers were
      separated by heparin affinity chromatography and analyzed by vWF antigen enzyme
      linked immunosorbent assay (ELISA), ristocetin cofactor activity test, both
      vWF:CBAs, and a multimer analysis. From our data we conclude that the assay with
      pepsin-digested collagen (human, type III) that was covalently linked to
      preactivated microtiter plates (vWF:CBAPDC) revealed a higher affinity for low
      and medium vWF multimers, whereas the assay with collagen fibrils (equine, type
      I) that were adsorbed to microtiter plates (vWF:CBACF) predominantly bound high
      vWF multimers. Based on results reported by others, we assume that the
      discrepancies between both vWF:CBAs were not related to the type and species of
      collagen used. Taken together our results imply rather that fragmentation of
      collagen by pepsin digestion or subsequent covalent linkage to the microtiter
      plate, or both, increased the affinity for low and medium vWF multimers, whereas
      the fibrillar structure of collagen was required for the binding of high vWF
      multimers, which exhibit the highest physiological activity in primary
      hemostasis.

PMID- 11992238
TI  - Comparative study on collagen-binding enzyme-linked immunosorbent assay and
      ristocetin cofactor activity assays for detection of functional activity of von
      Willebrand factor.
AB  - For more than two decades, the ristocetin cofactor (RCo) assay, which measures
      the von Willebrand factor (vWF)-mediated agglutination of platelets in the
      presence of the antibiotic ristocetin, has been the most common method for
      measuring the functional activity of vWF. There is, however, general agreement
      among clinical analysts that this method has major practical disadvantages in
      performance and reproducibility. Today, collagen-binding assays (CBA) based on
      the enzyme-linked immunosorbent assay (ELISA) technique that measure the
      interaction of vWF and collagen are an alternative analytic procedure based on a
      more physiological function than that of the RCo procedure. We used both assay
      systems in a comparative study to assess the functional activity of vWF in plasma
      as well as in therapeutic preparations. We measured RCo activities of plasma from
      healthy donors and patients with different types of von Willebrand disease (vWD)
      and of vWF as a drug substance in factor (F) VIII/vWF concentrates using both the
      aggregometric and the macroscopic methods. In addition, we measured collagen
      binding activity (vWF:CB) using a recently developed commercially available CBA
      system. To investigate the relation between the structure and the functional
      activity of vWF, we isolated vWF species with different numbers of multimers from
      FVIII/vWF concentrates by affinity chromatography on immobilized heparin. The
      vWF:RCo and vWF:CB of the different fractions were measured, and the multimeric
      structure of vWF was analyzed by sodium dodecyl sulfate (SDS) agarose gel
      electrophoresis. (vWF:CB and vWF:RCo are part of the nomenclature proposed by the
      International Society on Thrombosis and Hemostasis Scientific and Standardization
      Committee [ISTH SSC] subcommittee on von Willebrand factor, in Maastricht,
      Germany, June 16, 2000.) Measurement of functional vWF activity by CBA can be
      carried out with substantially higher interassay reproducibility than can
      measurement of RCo. Both assay systems can be used for diagnosis and subtyping of
      vWD, but CBA is more sensitive than either of the two RCo methods. The analysis
      of vWF multimers in the different fractions obtained by affinity chromatography
      on heparin Sepharose showed that the activity measured both with RCo assay and
      CBA correlated with the degree of multimerization. Our results suggest that
      measurement of the functional activity of vWF by the RCo procedure can be
      replaced by the more reliable CBA, reflecting the physiological hemostatic
      activity of vWF. The CBA method appears not only to be more sensitive and easier
      to carry out than the RCo method is but also to have a higher reproducibility and
      allow better standardization.

PMID- 11992239
TI  - A Reliable von Willebrand factor: ristocetin cofactor enzyme-linked immunosorbent
      assay to differentiate between type 1 and type 2 von Willebrand disease.
AB  - von Willebrand disease (vWD) is the most common hereditary bleeding disorder due
      to either a qualitative or a quantitative defect in von Willebrand factor (vWF).
      vWF is a multimeric plasma protein that plays an important role in (1) primary
      hemostasis, by sustaining indirect platelet adhesion especially at high shear
      rates, and in (2) secondary hemostasis, by protecting factor VIIIc (FVIIIc) from
      degradation. A correct diagnosis of vWD is based on the accurate identification
      of one of the six different subtypes (type 1, 2A, 2B, 2M, 2N, 3). To do this,
      different laboratory tests are available. One aspect of the identification is the
      discrimination between type 1 and type 2 (2A, 2B, and 2M) vWD. In type 1 vWD,
      both vWF levels (vWF:Ag) and vWF activity (vWF:RCof) are decreased; in type 2,
      the vWF:Ag level is normal or decreased and vWF:RCof is decreased. Thus, ratios
      of vWF:Ag to vWF:RiCof above 1 allow identifation of type 2 vWD patients. The
      currently used vWF:RCof test is an agglutination test in which patients' plasma
      is added to washed fixed control platelets in the presence of ristocetin and the
      extent of agglutination is measured. This test suffers from high interlaboratory
      and intralaboratory variability. We have recently shown that the same vWF:RCof
      can also be measured in an enzyme-linked immunosorbent assay (ELISA) with a low
      interassay and intraassay variability and can be used to identify patients
      suffering from vWD. We here show that our test allows the discrimination between
      type 1 and type 2 vWD patients.

PMID- 11992240
TI  - Assays of von Willebrand factor-cleaving protease: a test for diagnosis of
      familial and acquired thrombotic thrombocytopenic purpura.
AB  - Endothelial cells secrete von Willebrand factor (vWF) multimers that are larger
      than those found in the circulating plasma. These very large multimeric forms of
      vWF, capable of spontaneously binding to and agglutinating the blood platelets
      under conditions of high fluid shear rate, are degraded by a specific
      metalloprotease cleaving the peptide bond 842Tyr-843Met of the vWF subunit. The
      vWF-cleaving protease was found to be deficient in patients with familial
      thrombotic thrombocytopenic purpura (TTP). The acute events in these patients can
      be successfully treated and prophylactically prevented by repletion of the
      missing protease using fresh frozen plasma (FFP). In another, apparently more
      common, form of TTP, the protease deficiency is due to inhibiting circulating
      antibodies directed against the vWF-cleaving protease. Therapy of these patients
      should include immunosuppressive treatment in addition to plasma exchange and
      replacement with FFP. Normal activity of vWF-cleaving protease was established in
      patients with a clinically similar disorder: hemolytic-uremic syndrome (HUS). The
      level of vWF-cleaving protease activity is thus a laboratory parameter that
      provides important information for the differential diagnosis and treatment of
      patients with TTP/HUS. Several assays of vWF-cleaving protease have been
      described and are summarized here.

PMID- 11992241
TI  - Laboratory diagnosis of congenital von Willebrand disease.
AB  - Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or
      both, of the von Willebrand factor (vWF), a multimeric high-molecular
      glycoprotein (GP). Typically, it affects the primary hemostatic system, which is
      reflected by a mucocutaneous bleeding tendency simulating a platelet function
      defect. The vWF promotes its function in two ways: (1) by supporting platelet
      adhesion to the injured vessel wall under conditions of high shear forces and (2)
      by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the
      complexity of the disease, diagnosis of vWD is one of the most challenging of any
      coagulation disorder. The stepwise diagnosis of vWD includes patients and family
      history, screening procedures (bleeding time [BT], filter tests, platelet counts,
      activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen
      [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding
      [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests
      for final classification (multimeric analysis, FVIII binding capacity of vWF
      [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital
      vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was
      further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22),
      and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8%
      (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were
      type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n =
      36). The spectrum was completed with samples from patients with types 2D, 2C, 2C
      Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).

PMID- 11992242
TI  - Von Willebrand factor collagen-binding (activity) assay in the diagnosis of von
      Willebrand disease: a 15-year journey.
AB  - The correct diagnosis and classification of von Willebrand disease (vWD) is
      crucial because the presenting biological activity of von Willebrand factor (vWF)
      determines both the hemorrhagic risk and the subsequent clinical management. A
      variety of laboratory assays may be employed, not necessarily restricted to
      assessments of vWF. This article discusses the relative strengths and limitations
      of various functional or discriminatory vWF assays with a special focus on the
      vWF:collagen-binding activity (vWF:CBA) assay. This is a functional vWF assay
      that relies on the property of vWF adhesion to collagen. The vWF:CBA was first
      described approximately 15 years ago. The journey from that time point has been
      an interesting one, and the vWF:CBA is now gaining more widespread acceptance.
      There are now many published studies confirming the superiority of the vWF:CBA
      over the vWF ristocetin cofactor (vWF:RCof) activity as a functional screening
      diagnostic test process for vWD. However, both tests may be required in order to
      appropriately diagnose all forms of vWD. The relationship of these assays with
      multimer analysis is also discussed. In summary, an optimized vWF:CBA detects
      primarily high-molecular-weight (HMW) vWF forms and probably only about 30% of
      the total plasma vWF pool detected by vWF antigen (vWF:Ag). Because these HMW vWF
      forms are missing in types 2A and 2B vWD, the vWF:CBA is extremely useful in the
      detection of these qualitative vWD subtypes. In addition, however, concordance of
      vWF:CBA with vWF:Ag in unison with low vWF levels may alternatively suggest a
      type 1 vWD, and an absence of both vWF:Ag and vWF:CBA will suggest type 3 vWD.
      The vWF:CBA is also being investigated in various disease states, as is its
      usefulness as an effective marker of functional HMW vWF in both desmopressin
      (DDAVP) and factor-concentrate therapy in vWD.

PMID- 11992243
TI  - Successful treatment of patients with von Willebrand disease using a high-purity
      double-virus inactivated factor VIII/von Willebrand factor concentrate
      (Immunate).
AB  - Fourteen patients with different types of von Willebrand disease (vWD) having
      acute bleeds or elective surgery were treated with Immunate(sound recording
      copyright sign), a double-virus inactivated factor VIII/von Willebrand factor
      (FVIII/vWF) concentrate. The concentrate was applied as a bolus or via continuous
      infusion. FVIII activity (FVIIIc), vWF antigen (vWF:Ag), ristocetin cofactor
      activity (vWF:RCo), collagen binding activity (vWF:CB), activated partial
      thromboplastin time (aPTT), and von Willebrand multimers (vW-multimers) were
      monitored for 48 hours. Pharmacokinetic analyses were performed. The clinical
      efficacy was rated excellent or good. Bleeding complications occurred in 3
      patients due to an additional FXIII deficiency in one patient, to a surgically
      induced bleed in another patient, and a rather short substitution period in the
      third patient. There were no serious adverse experiences. One patient showed a
      phlebitic reaction at the site of venous access after more than 100 hours of
      continuous infusion, requiring a change to application via bolus.

PMID- 11992244
TI  - Recombinant von Willebrand factor-insight into structure and function through
      infusion studies in animals with severe von Willebrand disease.
AB  - We used a canine and a murine model of von Willebrand disease (vWD) to study the
      in vivo effects of recombinant von Willebrand factor (vWF). Two preparations were
      used: (1) a fully processed mature vWF; this was achieved by coexpression of
      furin. (2) A preparation containing unprocessed pro-vWF, the propeptide still
      covalently linked to mature vWF. Both preparations induced an increase in canine
      and murine factor VIII:C (FVIII), which was sustained even when vWF antigen had
      been removed from the circulation. vWF multimers were analyzed in the plasma
      samples after infusion using ultra high-resolution 3% agarose gels to allow the
      separation of homoforms and heteroforms of the vWF polymers. Administration of
      pro-vWF to dogs with severe vWD resulted in the removal of the propeptide and
      maturation of vWF in the circulation, indicating that the propeptide cleavage
      from unprocessed vWF can occur extracellularly. This suggests that the vWF
      propeptide, besides being derived from the Weibel-Palade bodies of endothelial
      cells after stimulation, can also be cleaved by pro-vWF in plasma. Using a murine
      model of vWD, the involvement of the low-density lipoprotein receptor-related
      protein (LRP) in the clearance of FVIII was established. The low levels of FVIII
      observed in the absence of vWF are due to an enhanced clearance of FVIII by
      binding to LRP and removal from the circulation through endocytosis.
      Administration of the receptor-associated protein (RAP) as a recombinant fusion
      protein to vWF knockout mice significantly improved the in vivo recovery of
      recombinant FVIII and the survival time of otherwise rapidly cleared FVIII.

PMID- 11992245
TI  - Acquired von Willebrand syndrome: experience from 2 years in a single laboratory
      compared with data from the literature and an international registry.
AB  - Acquired von Willebrand syndrome (avWS) has gained more attention during the last
      years. An International Registry has been compared with the literature. It could
      be shown that the data collected from 123 publications compared well with the
      data from the registry, albeit with differences in the number of patients
      suffering from lymphoproliferative diseases and cardiovascular disorders, that
      were more prominent in the registry and the group of miscellaneous conditions
      underrepresented in the registry. Our data are clearly different for the
      lymphoproliferative diseases with only four patients in 2 years. These patients
      usually suffer from severe bleeding complications together with low to very low
      factor VIII/von Willebrand factor (FVIII/vWF) concentrations and thus will not go
      undiagnosed. In contrast to this, patients with cardiovascular disorders usually
      bleed only during surgical procedures or catheter procedures. At that time they
      have increased vWF parameters. Because of this and because the acute bleeding is
      of limited duration and usually not life threatening, many of them are discharged
      without a proper diagnosis and are only rarely referred to a specialized
      diagnostic work-up thereafter. In conclusion, avWS, although not a frequent
      disease, is nevertheless clearly underdiagnosed. This should be addressed in
      future prospective studies.

PMID- 11992247
TI  - A rheostat model for a rapid and reversible form of imprinting-dependent
      evolution.
AB  - The evolutionary advantages of genomic imprinting are puzzling. We propose that
      genomic imprinting evolved as a mechanism that maximizes the interindividual
      variability in the rates of gene expression for dosage-sensitive loci that, with
      minimal unrelated deleterious effects, can alter the phenotype over a wide
      continuum. We hypothesize (1) that genomic imprinting provides a previously
      suggested haploid selective advantage (HSA); (2) that many imprinted genes have
      evolved mechanisms that facilitate quantitative hypervariability (QH) of gene
      expression; (3) that the combination of HSA and QH makes possible a rapid and
      reversible form of imprinting-dependent evolution (IDE) that can mediate changes
      in phenotype; and (4) that this enhanced adaptability to a changing environment
      provides selective advantage to the population, as an assisted form of evolution.
      These mechanisms may have provided at least one of the driving forces for the
      evolution of genomic imprinting in mammals. The rheostat model suggests that both
      genetic and epigenetic variants can contribute to an integrated mechanism of
      mixed Mendelian and non-Mendelian inheritance and suggests the possibility that
      the majority of variants are not intrinsically deleterious but, depending on the
      environment, are each potentially advantageous. Moreover, this would be a
      reversible form of evolution, with the ability not only to protect a silent
      allele from selection for many generations but to reactivate and expand it in the
      population quickly.

PMID- 11992248
TI  - Systematic evaluation of map quality: human chromosome 22.
AB  - Marker positions on nine genetic linkage, radiation hybrid, and integrated maps
      of human chromosome 22 were compared with their corresponding positions in the
      completed DNA sequence. The proportion of markers whose map position is <250 kb
      from their respective sequence positions ranges from 100% to 35%. Several
      discordant markers were identified, as well as four regions that show common
      inconsistencies across multiple maps. These shared discordant regions surround
      duplicated DNA segments and may indicate mapping or assembly errors due to
      sequence homology. Recombination-rate distributions along the chromosome were
      also evaluated, with male and female meioses showing significantly different
      patterns of recombination, including an 8-Mb male recombination desert. The
      distributions of radiation-induced chromosome breakage for the GB4 and the G3
      radiation hybrid panels were also evaluated. Both panels show fluctuations in
      breakage intensity, with different regions of significantly elevated rates of
      breakage. These results provide support for the common assumption that radiation
      induced breaks are generally randomly distributed. The present studies detail the
      limitations of these important map resources and should prove useful for
      clarifying potential problems in the human maps and sequence assemblies, as well
      as for mapping and sequencing projects in and across other species.

PMID- 11992249
TI  - Founding mothers of Jewish communities: geographically separated Jewish groups
      were independently founded by very few female ancestors.
AB  - We have analyzed the maternally inherited mitochondrial DNA from each of nine
      geographically separated Jewish groups, eight non-Jewish host populations, and an
      Israeli Arab/Palestinian population, and we have compared the differences found
      in Jews and non-Jews with those found using Y-chromosome data that were obtained,
      in most cases, from the same population samples. The results suggest that most
      Jewish communities were founded by relatively few women, that the founding
      process was independent in different geographic areas, and that subsequent
      genetic input from surrounding populations was limited on the female side. In
      sharp contrast to this, the paternally inherited Y chromosome shows diversity
      similar to that of neighboring populations and shows no evidence of founder
      effects. These sex-specific differences demonstrate an important role for culture
      in shaping patterns of genetic variation and are likely to have significant
      epidemiological implications for studies involving these populations. We
      illustrate this by presenting data from a panel of X-chromosome microsatellites,
      which indicates that, in the case of the Georgian Jews, the female-specific
      founder event appears to have resulted in elevated levels of linkage
      disequilibrium.

PMID- 11992250
TI  - Unusual splice-site mutations in the RSK2 gene and suggestion of genetic
      heterogeneity in Coffin-Lowry syndrome.
AB  - Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation
      that is characterized, in male patients, by psychomotor and growth retardation
      and various skeletal anomalies. Typical facial changes and specific clinical and
      radiological hand aspects exhibited by patients are essential clues for the
      diagnosis. CLS is caused by mutations in a gene that is located in Xp22.2 and
      that encodes RSK2, a growth-factor-regulated protein kinase. RSK2 mutations are
      extremely heterogeneous and lead to premature termination of translation and/or
      loss of phosphotransferase activity. Surprisingly, among a series of 250 patients
      screened by single-strand conformation polymorphism (SSCP) analysis, in whom a
      clinical diagnosis of CLS was made, no mutations were detected in 66% (165) of
      the patients. To determine what proportion of these latter patients have a RSK2
      mutation that has not been detected and what proportion have different disorders
      that are phenotypically similar to CLS, we have, in the present article,
      investigated, by western blot analysis and in vitro kinase assay, cell lines from
      26 patients in whom no mutation was previously identified by SSCP analysis. This
      approach allowed us to identify seven novel RSK2 mutations: two changes in the
      coding sequence of RSK2, one intragenic deletion, and four unusual intronic
      nucleotide substitutions that do not affect the consensus GT or AG splice sites.
      We have also determined the nucleotide sequence of the promoter region of the
      RSK2 gene, and we have screened it for mutations. No disease-causing nucleotide
      change was identified, suggesting that mutations affecting the promoter region
      are unlikely to account for a large number of patients with CLS. Finally, our
      results provide evidence that some patients have a disease that is phenotypically
      very similar to CLS, which is not caused by RSK2 defects. This suggests that
      there are defects in either additional genes or combinations of genes that may
      result in a CLS-like phenotype.

PMID- 11992251
TI  - Minimum-recombinant haplotyping in pedigrees.
AB  - This article presents a six-rule algorithm for the reconstruction of multiple
      minimum-recombinant haplotype configurations in pedigrees. The algorithm has
      three major features: First, it allows exhaustive search of all possible
      haplotype configurations under the criterion that there are minimum recombinants
      between markers. Second, its computational requirement is on the order of
      O(J(2)L(3)) in current implementation, where J is the family size and L is the
      number of marker loci under analysis. Third, it applies to various pedigree
      structures, with and without consanguinity relationship, and allows missing
      alleles to be imputed, during the haplotyping process, from their identical-by
      descent copies. Haplotyping examples are provided using both published and
      simulated data sets.

PMID- 11992252
TI  - Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital
      muscular dystrophy.
AB  - Ullrich congenital muscular dystrophy (UCMD) is an autosomal recessive disorder
      characterized by generalized muscular weakness, contractures of multiple joints,
      and distal hyperextensibility. Homozygous and compound heterozygous mutations of
      COL6A2 on chromosome 21q22 have recently been shown to cause UCMD. We performed a
      genomewide screening with microsatellite markers in a consanguineous family with
      three sibs affected with UCMD. Linkage of the disease to chromosome 2q37 was
      found in this family and in two others. We analyzed COL6A3, which encodes the
      alpha3 chain of collagen VI, and identified one homozygous mutation per family.
      In family I, the three sibs carried an A-->G transition in the splice-donor site
      of intron 29 (6930+5A-->G), leading to the skipping of exon 29, a partial
      reduction of collagen VI in muscle biopsy, and an intermediate phenotype. In
      family II, the patient had an unusual mild phenotype, despite a nonsense
      mutation, R465X, in exon 5. Analysis of the patient's COL6A3 transcripts showed
      the presence of various mRNA species-one of which lacked several exons, including
      the exon containing the nonsense mutation. The deleted splice variant encodes
      collagen molecules that have a shorter N-terminal domain but that may assemble
      with other chains and retain a functional role. This could explain the mild
      phenotype of the patient who was still ambulant at age 18 years and who showed an
      unusual combination of hyperlaxity and finger contractures. In family III, the
      patient had a nonsense mutation, R2342X, causing absence of collagen VI in muscle
      and fibroblasts, and a severe phenotype, as has been described in patients with
      UCMD. Mutations in COL6A3 are described in UCMD for the first time and illustrate
      the wide spectrum of phenotypes which can be caused by collagen VI deficiency.

PMID- 11992253
TI  - Patterns of meiotic recombination in human fetal oocytes.
AB  - Abnormal patterns of meiotic recombination (i.e., crossing-over) are believed to
      increase the risk of chromosome nondisjunction in human oocytes. To date,
      information on recombination has been obtained using indirect, genetic methods.
      Here we use an immunocytological approach, based on detection of foci of a DNA
      mismatch-repair protein, MLH1, on synaptonemal complexes at prophase I of
      meiosis, to provide the first direct estimate of the frequency of meiotic
      recombination in human oocytes. At pachytene, the stage of maximum homologous
      chromosome pairing, we found a mean of 70.3 foci (i.e., crossovers) per oocyte,
      with considerable intercell variability (range 48-102 foci). This mean equates to
      a genetic-map length of 3,515 cM. The numbers and positions of foci were
      determined for chromosomes 21, 18, 13, and X. These chromosomes yielded means of
      1.23 foci (61.5 cM), 2.36 foci (118 cM), 2.5 foci (125 cM), and 3.22 foci (161
      cM), respectively. The foci were almost invariably located interstitially and
      were only occasionally located close to chromosome ends. These data confirm the
      large difference, in recombination frequency, between human oocytes and
      spermatocytes and demonstrate a clear intersex variation in distribution of
      crossovers. In a few cells, chromosomes 21 and 18 did not have any foci (i.e.,
      were presumptively noncrossover); however, configurations that lacked foci were
      not observed for chromosomes 13 and X. For the latter two chromosome pairs, the
      only instances of absence of foci were observed in abnormal cells that showed
      chromosome-pairing errors affecting these chromosomes. We speculate that these
      abnormal fetal oocytes may be the source of the nonrecombinant chromosomes 13 and
      X suggested, by genetic studies, to be associated with maternally derived
      chromosome nondisjunction.

PMID- 11992254
TI  - Power calculations for genetic association studies using estimated probability
      distributions.
AB  - The determination of the power of-or of an appropriate sample size for-genetic
      association studies that exploit linkage disequilibrium requires many
      assumptions. Some of the more important assumptions include the linkage
      disequilibrium strength among alleles at the observed marker-locus sites and a
      potential trait-influencing locus, the frequencies of the marker locus and trait
      influencing alleles, and the ultimate density of the marker locus "map" (i.e.,
      the number of bases between marker loci) necessary in order to identify, with
      some confidence, trait-influencing alleles. I consider an approach to assessment
      of the power and sample-size requirements of genetic case-control association
      study designs that makes use of empirically derived estimates of the
      distributions of important parameters often assumed to take on arbitrary values.
      My proposed methodology is extremely general and flexible and ultimately can
      provide realistic answers to questions such as "How many markers and/or how many
      individuals might it take to identify, with confidence, a disease gene, via
      linkage-disequilibrium and association methods from a candidate region or whole
      genome perspective?" I showcase aspects of the proposed methodology, using
      information abstracted from the literature.

PMID- 11992255
TI  - Genomewide comparison of DNA sequences between humans and chimpanzees.
AB  - A total of 8,859 DNA sequences encompassing approximately 1.9 million base pairs
      of the chimpanzee genome were sequenced and compared to corresponding human DNA
      sequences. Although the average sequence difference is low (1.24%), the extent of
      changes is markedly different among sites and types of substitutions. Whereas
      approximately 15% of all CpG sites have experienced changes between humans and
      chimpanzees, owing to a 23-fold excess of transitions and a 7-fold excess of
      transversions, substitutions at other sites vary in frequency, between 0.1% and
      0.5%. If the nucleotide diversity in the common ancestral species of humans and
      chimpanzees is assumed to have been about fourfold higher than in contemporary
      humans, all possible comparisons between autosomes and X and Y chromosomes result
      in estimates of the ratio between male and female mutation rates of approximately
      3. Thus, the relative time spent in the male and female germlines may be a major
      determinant of the overall accumulation of nucleotide substitutions. However,
      since the extent of divergence differs significantly among autosomes, additional
      unknown factors must also influence the accumulation of substitutions in the
      human genome.

PMID- 11992256
TI  - New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and
      familial cold urticaria: a novel mutation underlies both syndromes.
AB  - Mutations of CIAS1 have recently been shown to underlie familial cold urticaria
      (FCU) and Muckle-Wells syndrome (MWS), in three families and one family,
      respectively. These rare autosomal dominant diseases are both characterized by
      recurrent inflammatory crises that start in childhood and that are generally
      associated with fever, arthralgia, and urticaria. The presence of sensorineural
      deafness that occurs later in life is characteristic of MWS. Amyloidosis of the
      amyloidosis-associated type is the main complication of MWS and is sometimes
      associated with FCU. In FCU, cold exposure is the triggering factor of the
      inflammatory crisis. We identified CIAS1 mutations, all located in exon 3, in
      nine unrelated families with MWS and in three unrelated families with FCU,
      originating from France, England, and Algeria. Five mutations--namely, R260W,
      D303N, T348M, A439T, and G569R--were novel. The R260W mutation was identified in
      two families with MWS and in two families with FCU, of different ethnic origins,
      thereby demonstrating that a single CIAS1 mutation may cause both syndromes. This
      result indicates that modifier genes are involved in determining either a MWS or
      a FCU phenotype. The finding of the G569R mutation in an asymptomatic individual
      further emphasizes the importance of such modifier a gene (or genes) in
      determining the disease phenotype. Identification of this gene (or these genes)
      is likely to have significant therapeutic implications for these severe diseases.

PMID- 11992257
TI  - Stable variants of sperm aneuploidy among healthy men show associations between
      germinal and somatic aneuploidy.
AB  - Repeated semen specimens from healthy men were analyzed by sperm fluorescence in
      situ hybridization (FISH), to identify men who consistently produced elevated
      frequencies of aneuploid sperm and to determine whether men who were identified
      as stable variants of sperm aneuploidy also exhibited higher frequencies of
      aneuploidy in their peripheral blood lymphocytes. Seven semen specimens were
      provided by each of 15 men over a 2-year period and were evaluated by the X-Y-8
      multicolor sperm FISH method (i.e., approximately 1,050,000 sperm were analyzed
      from 105 specimens). Three men were identified as stable aneuploidy variants
      producing significantly higher frequencies of XY, disomy X, disomy Y, disomy 8,
      and/or diploid sperm over time. In addition, one man and three men were
      identified as sperm-morphology and sperm-motility variants, respectively. Strong
      correlations were found between the frequencies of sperm with autosomal and sex
      chromosome aneuploidies and between the two types of meiosis II diploidy; but not
      between sperm aneuploidy and semen quality. A significant association was found
      between the frequencies of sex-chromosome aneuploidies in sperm and lymphocytes
      in a subset of 10 men (r2=0.67, P=.004), especially between XY sperm and sex
      chromosome aneuploidy in lymphocytes (r2=0.70, P=.003). These findings suggest
      that certain apparently healthy men can produce significantly higher frequencies
      of both aneuploid sperm and lymphocytes. Serious long-term somatic and
      reproductive health consequences may include increased risks of aneuploidy
      related somatic diseases and of having children with paternally transmitted
      aneuploidies, such as Klinefelter, Turner, triple-X, and XYY syndromes.

PMID- 11992258
TI  - Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and
      DXS1357E: a novel neonatal phenotype similar to peroxisomal biogenesis disorders.
AB  - X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1
      resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein
      [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette
      transporter superfamily. Individuals with ABCD1 mutations accumulate very-long
      chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the
      most devastating form of the disease. These children have the earliest onset (age
      7.2 +/- 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset
      does not occur at <3 years of age. Individuals with either peroxisomal biogenesis
      disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal beta
      oxidation pathway--disorders such as acyl CoA oxidase deficiency and bifunctional
      protein deficiency--also accumulate VLCFA, but they present during the neonatal
      period. Until now, it has been possible to distinguish unequivocally between
      individuals with these autosomal recessively inherited syndromes and individuals
      with ABCD1 mutations, on the basis of the clinical presentation and measurement
      of other biochemical markers. We have identified three newborn boys who had
      clinical symptoms and initial biochemical results consistent with PBD or SED. In
      further study, however, we showed that they lacked ALDP, and we identified
      deletions that extended into the promoter region of ABCD1 and the neighboring
      gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been
      described previously. We propose that the term "contiguous ABCD1 DXS1357E
      deletion syndrome" (CADDS) be used to identify this new contiguous-gene syndrome.
      The three patients with CADDS who are described here have important implications
      for genetic counseling, because individuals with CADDS may previously have been
      misdiagnosed as having an autosomal recessive PBD or SED

PMID- 11992259
TI  - Paternally transmitted FMR1 alleles are less stable than maternally transmitted
      alleles in the common and intermediate size range.
AB  - Fragile X syndrome, a form of X-linked mental retardation, results from the
      hyperexpansion of a CGG trinucleotide repeat located in the 5' untranslated
      region of the fragile X mental retardation (FMR1) gene. Relatively little is
      known about the initial mutation that causes a stable allele to become unstable
      and, eventually, to expand to the full mutation. In the present study, we have
      examined 1,452 parent-child transmissions of alleles of common (< or =39 repeats)
      or intermediate (40-59 repeats) sizes to study the initial mutation events. Of
      these, 201 have been sequenced and haplotyped. Using logistic regression
      analysis, we found that parental origin of transmission, repeat size (for
      unsequenced alleles), and number of the 3' CGGs (for sequenced alleles) were
      significant risk factors for repeat instability. Interestingly, transmission of
      the repeat through males was less stable than that through females, at the common
      and intermediate-size level. This pattern differs from that seen for premutation
      size alleles: paternally transmitted alleles are far more stable than maternally
      transmitted alleles. This difference that depends on repeat size suggests either
      a different mutational mechanism of instability or an increase in selection
      against sperm as their repeat size increases.

PMID- 11992260
TI  - A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of
      families with X-linked retinitis pigmentosa.
AB  - X-linked retinitis pigmentosa (XLRP) is a clinically and genetically
      heterogeneous degenerative disease of the retina. At least five loci have been
      mapped for XLRP; of these, RP2 and RP3 account for 10%-20% and 70%-90% of
      genetically identifiable disease, respectively. However, mutations in the
      respective genes, RP2 and RPGR, were detected in only 10% and 20% of families
      with XLRP. Mutations in an alternatively spliced RPGR exon, ORF15, have recently
      been shown to account for 60% of XLRP in a European cohort of 47 families. We
      have performed, in a North American cohort of 234 families with RP, a
      comprehensive screen of the RP2 and RPGR (including ORF15) genes and their 5'
      upstream regions. Of these families, 91 (39%) show definitive X-linked
      inheritance, an additional 88 (38%) reveal a pattern consistent with X-linked
      disease, and the remaining 55 (23%) are simplex male patients with RP who had an
      early onset and/or severe disease. In agreement with the previous studies, we
      show that mutations in the RP2 gene and in the original 19 RPGR exons are
      detected in <10% and approximately 20% of XLRP probands, respectively. Our
      studies have revealed RPGR-ORF15 mutations in an additional 30% of 91 well
      documented families with X-linked recessive inheritance and in 22% of the total
      234 probands analyzed. We suggest that mutations in an as-yet-uncharacterized
      RPGR exon(s), intronic changes, or another gene in the region might be
      responsible for the disease in the remainder of this North American cohort. We
      also discuss the implications of our studies for genetic diagnosis, genotype
      phenotype correlations, and gene-based therapy.

PMID- 11992261
TI  - PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype
      correlation, and phenotypic heterogeneity.
AB  - Noonan syndrome (NS) is a developmental disorder characterized by facial
      dysmorphia, short stature, cardiac defects, and skeletal malformations. We
      recently demonstrated that mutations in PTPN11, the gene encoding the non
      receptor-type protein tyrosine phosphatase SHP-2 (src homology region 2-domain
      phosphatase-2), cause NS, accounting for approximately 50% of cases of this
      genetically heterogeneous disorder in a small cohort. All mutations were missense
      changes and clustered at the interacting portions of the amino-terminal src
      homology 2 (N-SH2) and protein tyrosine phosphatase (PTP) domains. A gain of
      function was postulated as a mechanism for the disease. Here, we report the
      spectrum and distribution of PTPN11 mutations in a large, well-characterized
      cohort with NS. Mutations were found in 54 of 119 (45%) unrelated individuals
      with sporadic or familial NS. There was a significantly higher prevalence of
      mutations among familial cases than among sporadic ones. All defects were
      missense, and several were recurrent. The vast majority of mutations altered
      amino acid residues located in or around the interacting surfaces of the N-SH2
      and PTP domains, but defects also affected residues in the C-SH2 domain, as well
      as in the peptide linking the N-SH2 and C-SH2 domains. Genotype-phenotype
      analysis revealed that pulmonic stenosis was more prevalent among the group of
      subjects with NS who had PTPN11 mutations than it was in the group without them
      (70.6% vs. 46.2%; P<.01), whereas hypertrophic cardiomyopathy was less prevalent
      among those with PTPN11 mutations (5.9% vs. 26.2%; P<.005). The prevalence of
      other congenital heart malformations, short stature, pectus deformity,
      cryptorchidism, and developmental delay did not differ between the two groups. A
      PTPN11 mutation was identified in a family inheriting Noonan-like/multiple giant
      cell lesion syndrome, extending the phenotypic range of disease associated with
      this gene.

PMID- 11992262
TI  - The gene encoding nicastrin, a major gamma-secretase component, modifies risk for
      familial early-onset Alzheimer disease in a Dutch population-based sample.
AB  - Nicastrin regulates gamma-secretase cleavage of the amyloid precursor protein by
      forming complexes with presenilins, in which most mutations causing familial
      early-onset Alzheimer disease (EOAD) have been found. The gene encoding nicastrin
      (NCSTN) maps to 1q23, a region that has been linked and associated with late
      onset Alzheimer disease (LOAD) in various genome screens. In 78 familial EOAD
      cases, we found 14 NCSTN single-nucleotide polymorphisms (SNPs): 10 intronic
      SNPs, 3 silent mutations, and 1 missense mutation (N417Y). N417Y is unlikely to
      be pathogenic, since it did not alter amyloid beta secretion in an in vitro assay
      and its frequency was similar in case and control subjects. However, SNP
      haplotype estimation in two population-based series of Dutch patients with EOAD
      (n=116) and LOAD (n=240) indicated that the frequency of one SNP haplotype (HapB)
      was higher in the group with familial EOAD (7%), compared with the LOAD group
      (3%) and control group (3%). In patients with familial EOAD without the APOE
      epsilon4 allele, the HapB frequency further increased, to 14%, resulting in a
      fourfold increased risk (odds ratio = 4.1; 95% confidence interval 1.2-13.3;
      P=.01). These results are compatible with an important role of gamma-secretase
      dysfunction in the etiology of familial EOAD.

PMID- 11992263
TI  - Apolipoprotein E-promoter single-nucleotide polymorphisms affect the phenotype of
      primary open-angle glaucoma and demonstrate interaction with the myocilin gene.
AB  - Primary open-angle glaucoma (POAG) is an optic neuropathy that has a high
      worldwide prevalence and that shows strong evidence of complex inheritance. The
      myocilin (MYOC) gene is the only one that has thus far been shown to have
      mutations in patients with POAG. Apolipoprotein E (APOE) plays an essential role
      in lipid metabolism, and the APOE gene has been involved in neuronal degeneration
      that occurs in Alzheimer disease (AD). Here, we report that two APOE-promoter
      single-nucleotide polymorphisms (SNPs) previously associated with AD also modify
      the POAG phenotype. APOE(-219G) is associated with increased optic nerve damage,
      as reflected by increased cup:disk ratio and visual field alteration. In
      addition, APOE(-491T), interacting at a highly significant level with an SNP in
      the MYOC promoter, MYOC(-1000G), is associated with increased intraocular
      pressure (IOP) and with limited effectiveness of IOP-lowering treatments in
      patients with POAG. Together, these findings establish APOE as a potent modifier
      for POAG, which could explain the linkage to chromosome 19q previously observed
      by use of a genome scan for this condition and an increased frequency of glaucoma
      in patients with AD. The findings also shed new light on potential mechanisms of
      optic nerve damage and of IOP regulation in POAG.

PMID- 11992264
TI  - Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget
      disease of bone.
AB  - Paget disease of bone (PDB) is a common disorder characterized by focal and
      disorganized increases of bone turnover. Genetic factors are important in the
      pathogenesis of PDB. We and others recently mapped the third locus associated
      with the disorder, PDB3, at 5q35-qter. In the present study, by use of 24 French
      Canadian families and 112 unrelated subjects with PDB, the PDB3 locus was
      confined to approximately 300 kb. Within this interval, two disease-related
      haplotype signatures were observed in 11 families and 18 unrelated patients. This
      region encoded the ubiquitin-binding protein sequestosome 1 (SQSTM1/p62), which
      is a candidate gene for PDB because of its association with the NF-kappaB
      pathway. Screening SQSTM1/p62 for mutations led to the identification of a
      recurrent nonconservative change (P392L) flanking the ubiquitin-associated domain
      (UBA) (position 394-440) of the protein that was not present in 291 control
      individuals. Our data demonstrate that two independent mutational events at the
      same position in SQSTM1/p62 caused PDB in a high proportion of French Canadian
      patients.

PMID- 11992265
TI  - Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification
      of the true defect at the level of d-bifunctional protein.
AB  - In this report, we reinvestigate the only patient ever reported with a deficiency
      of peroxisomal 3-ketoacyl-CoA thiolase (THIO). At the time when they were
      described, the abnormalities in this patient, which included accumulation of very
      long-chain fatty acids and the bile-acid intermediate trihydroxycholestanoic
      acid, were believed to be the logical consequence of a deficiency of the
      peroxisomal beta-oxidation enzyme THIO. In light of the current knowledge of the
      peroxisomal beta-oxidation system, however, the reported biochemical aberrations
      can no longer be explained by a deficiency of this thiolase. In this study, we
      show that the true defect in this patient is at the level of d-bifunctional
      protein (DBP). Immunoblot analysis revealed the absence of DBP in postmortem
      brain of the patient, whereas THIO was normally present. In addition, we found
      that the patient had a homozygous deletion of part of exon 3 and intron 3 of the
      DBP gene, resulting in skipping of exon 3 at the cDNA level. Our findings imply
      that the group of single-peroxisomal beta-oxidation-enzyme deficiencies is
      limited to straight-chain acyl-CoA oxidase, DBP, and alpha-methylacyl-CoA
      racemase deficiency and that there is no longer evidence for the existence of
      THIO deficiency as a distinct clinical entity.

PMID- 11992266
TI  - Genetic evidence for the expansion of Arabian tribes into the Southern Levant and
      North Africa.

PMID- 11992267
TI  - SMN dosage analysis and risk assessment for spinal muscular atrophy.

PMID- 11992269
TI  - The power of multivariate quantitative-trait loci linkage analysis is influenced
      by the correlation between variables.

PMID- 11992270
TI  - The National Institutes of Health announces online availability of "Points to
      consider when planning a genetic study that involves members of named
      populations".

PMID- 11992271
TI  - Age-related decrease in adenovirus-specific T cell responses.
AB  - Infections with persistent viruses, such as cytomegalovirus (CMV) or adenovirus,
      are not, in general, clinically apparent but may cause serious complications in
      the immunocompromised host. As has been shown for CMV, the cellular arm of the
      immune response is essential in controlling viral replication. However, cellular
      immunity toward adenoviruses has not been well characterized in humans. The aim
      of the present study was the quantitative and functional analysis of adenovirus
      specific T cell responses from 171 healthy individuals and 59 long-term renal
      transplant recipients by use of flow-cytometric, as well as standard
      proliferation and enzyme-linked immunosorbant, assays. Adenovirus-specific
      immunity is dominated by CD4 T cells with memory/effector phenotype. Of interest,
      the frequency of adenovirus-specific T cells decreases significantly with age.
      This age-related decline indicates the eventual elimination of adenoviruses
      within a lifetime that may explain the well-known clinical observation of a
      predominant incidence of adenoviral complications in children and young adults,
      compared with older adults, after transplantation.

PMID- 11992272
TI  - Peripheral blood mononuclear cells from infants hospitalized because of
      respiratory syncytial virus infection express T helper-1 and T helper-2 cytokines
      and CC chemokine messenger RNA.
AB  - The cellular immune response to respiratory syncytial virus (RSV) infection was
      examined in infants aged 1-21 months who were hospitalized because of RSV
      infection or non-RSV-related illness. RSV- or control-stimulated peripheral blood
      mononuclear cells were examined to determine RSV-specific intracellular T helper
      1 (Th1) and T helper- 2 (Th2) cytokine expression, chemokine messenger RNA (mRNA)
      expression, and cell surface markers. Patients hospitalized because of RSV
      infection had increased numbers of CD16(+) and CD56(bright) cells and had RSV
      specific increases in Th1 (interleukin [IL]-2 and interferon-gamma) and Th2 (IL-4
      and IL-6) cytokines and CC chemokines (macrophage inflammatory protein [MIP]
      1alpha, MIP-1beta, and RANTES [regulated on activation, normally T cell expressed
      and secreted]) mRNA expression. The results suggest that RSV infection induces
      both Th1 and Th2 cytokine expression and CC chemokine expression.

PMID- 11992273
TI  - Intra-abdominal bacterial infection reactivates latent pulmonary cytomegalovirus
      in immunocompetent mice.
AB  - Critically ill surgery patients are susceptible to pulmonary reactivation of
      latent cytomegalovirus (CMV), but what triggers this reactivation is unknown.
      Immunosuppression and bacterial sepsis are thought to stimulate reactivation of
      CMV, and in this study it was hypothesized that immunosuppressive effects of
      surgery with or without concomitant bacterial infection may reactivate latent
      CMV. Mice infected with CMV were allowed to develop latent infections. Latently
      infected mice underwent a laparotomy with cecal ligation and puncture (CLP;
      n=30), a laparotomy alone (sham; n=10), or no surgery (control; n=5). Lung tissue
      homogenates were evaluated for viral activity, and, 2 and 3 weeks after CLP,
      lungs of 7 of 7 and 5 of 5 mice, respectively, showed reactivation of latent CMV.
      In contrast, lungs from all sham-operated animals and controls showed no viral
      reactivation. These findings demonstrate that surgery with subsequent intra
      abdominal bacterial infection reactivated CMV in lungs of latently infected mice.
      The mechanism of this reactivation is unknown but likely involves cytokines
      induced by sepsis.

PMID- 11992274
TI  - Close link between CD4+ and CD8+ T cell proliferation defects in patients with
      human immunodeficiency virus disease and relationship to extended periods of CD4+
      lymphopenia.
AB  - T cell proliferation failure is commonly associated with human immunodeficiency
      virus (HIV) infection. By examining T cell function on a single-cell basis, we
      found that CD4(+) T cell proliferation failure was often accompanied by CD8(+) T
      cell proliferation defects in patients with HIV disease. The defects are
      characterized by a proportional failure and reduced efficiency of precursor T
      cell proliferation after stimulation. In this study, patients who historically
      had low levels of circulating CD4(+) T cells were most likely to demonstrate
      cellular proliferation failure, regardless of current CD4(+) T cell counts. In
      contrast, neither historical nor current plasma HIV RNA levels were predictive of
      proliferation failure. These results suggest that mechanisms of T cell
      proliferation failure are more complex than can be explained by the direct
      effects of HIV replication and that therapeutic intervention to avoid prolonged
      periods of CD4(+) lymphopenia may be desirable for the preservation of immune
      function in patients with HIV disease.

PMID- 11992275
TI  - Persistence of human immunodeficiency virus (HIV) type 1 DNA in peripheral blood
      despite prolonged suppression of plasma HIV-1 RNA in children.
AB  - Human immunodeficiency virus (HIV) type 1 DNA in peripheral blood mononuclear
      cells (PBMC) was quantified in 31 children who received efavirenz, nelfinavir,
      and 1 or 2 nucleoside reverse-transcriptase inhibitors for > or =2 years and in
      whom undetectable plasma HIV-1 RNA levels (< 50 copies/mL) were sustained, to
      determine the usefulness of HIV-1 DNA as a marker of virus suppression. The
      median baseline HIV-1 DNA level was 750 copies/10(6) PBMC. After initiation of
      highly active antiretroviral therapy (HAART), HIV-1 DNA levels decreased
      gradually, reaching a plateau from week 80 through week 104 (median HIV-1 DNA
      level, 263 copies/10(6) PBMC). Children who had plasma HIV-1 RNA levels < 50
      copies/mL after receiving HAART for 8 weeks (n=16) had persistently lower
      quantities of intracellular HIV-1 DNA than children whose HIV-1 RNA levels
      reached < 50 copies/mL after 8 weeks of HAART (n=15). The median half-life for
      intracellular HIV-1 DNA was 60 weeks. Thus, despite prolonged maintenance of
      undetectable levels of plasma HIV-1 RNA, HIV-1 DNA remains detectable in PBMC of
      children and may be a useful marker of further virus suppression.

PMID- 11992276
TI  - On the role of Staphylococcus aureus sortase and sortase-catalyzed surface
      protein anchoring in murine septic arthritis.
AB  - Anchoring of Staphylococcus aureus surface protein to the cell wall is catalyzed
      by sortase, a transpeptidase. The contribution of staphylococcal surface proteins
      to establishment of infection was examined using a murine septic arthritis model.
      Intravenous inoculation of mice with the sortase-deficient mutant S. aureus
      strain SMK3 did not result in weight loss or severe septic arthritis, in contrast
      to the parent strain, S. aureus Newman. Direct inoculation of the sortase mutant
      into joint cavities also failed to cause severe synovitis or erosive arthritis.
      Furthermore, intravenous inoculation with staphylococci resulted in the rapid
      clearing of the sortase mutant from the bloodstream. This phenomenon demonstrates
      the involvement of host neutrophils; when these cells were depleted, sortase
      mutant staphylococci caused severe systemic infection, although not septic
      arthritis. These results suggest that sortase mutant staphylococci are
      significantly less virulent than the parent strain, Newman: the sortase mutant
      has decreased ability to reach target organs and, once there, to induce an
      inflammatory response.

PMID- 11992277
TI  - Gene therapy using a simian virus 40-derived vector inhibits the development of
      in vivo human immunodeficiency virus type 1 infection of severe combined
      immunodeficiency mice implanted with human fetal thymic and liver tissue.
AB  - To evaluate the in vivo efficacy of gene therapy for treating human
      immunodeficiency virus type 1 (HIV-1) infection, a novel simian virus (SV) 40
      derived vector gene delivery system that efficiently transduces human leukocytes
      was combined with a model using severe combined immunodeficiency mice infected
      with HIV-1 and implanted with human fetal thymic and liver tissue (thy/liv-SCID
      hu mice). The SV40-derived vector, SV(Aw), which encodes a variable fragment
      antibody recognizing HIV-1 integrase (IN#33),was injected into the human thymic
      grafts of thy/liv-SCID-hu mice and induced IN#33 expression in most of the
      thymocytes in the graft. After in vivo challenge with HIV-1, IN#33 expression
      inhibited in vivo HIV-1 infection, as evidenced by the markedly lower number of
      HIV-1-infected thymocytes detected in human thymic grafts injected with the
      SV(Aw) vector, compared with those injected with a control SV40-derived vector.
      Thus, these findings demonstrate the utility of this new mouse model system for
      assessing the in vivo efficacy of HIV-1-specific gene therapy. In addition, these
      data indicate that SV40-derived vectors may provide a system capable of efficient
      in vivo gene delivery.

PMID- 11992278
TI  - Proinflammatory responses to lipo-oligosaccharide of Neisseria meningitidis
      immunotype strains in relation to virulence and disease.
AB  - Inflammatory responses to lipo-oligosaccharide (LOS) contribute to the severity
      of meningococcal disease. Strains that express the L(3,7,9) LOS immunotypes are
      isolated from the majority of patients, but other immunotypes are isolated
      predominantly from carriers. Inflammatory responses elicited from a human
      monocytic cell line (THP-1) that had been pretreated with vitamin D3 (VD3) were
      compared after stimulation with purified LOSs from standard immunotype strains.
      The neutralizing effects of normal human serum and serum from mice immunized with
      strain B:2a:P1.5,2:L3 were compared. LOSs of immunotypes L3, L7, L8, and L9
      induced significantly higher levels of tumor necrosis factor-alpha and
      interleukin-6, compared with other immunotypes. Normal human serum neutralized
      the proinflammatory responses to LOSs of all immunotypes tested. Immune mouse
      serum neutralized inflammatory responses against LOSs from immunotypes with
      epitopes cross-reactive with L(3,7,9) moieties. Antibodies found in normal human
      serum and immune mouse serum to the oligosaccharide, core, and lipid A moieties
      of meningococcal endotoxin contribute to neutralizing activity.

PMID- 11992279
TI  - Epidemiological correlates of virulence genotype and phylogenetic background
      among Escherichia coli blood isolates from adults with diverse-source bacteremia.
AB  - Associations of virulence genotype and phylogenetic background with
      epidemiological factors (primary source of bacteremia, host compromise status,
      and hospital versus community origin) were assessed among 182 Escherichia coli
      blood isolates from adults with diverse-source bacteremia in comparison with
      fecal controls from the E. coli Reference collection. A continuum of virulence
      was found, from urinary and pulmonary source bacteremia isolates (high
      virulence), through "other" or unknown source bacteremia isolates (intermediate
      virulence), to fecal isolates (low virulence), with a corresponding graded
      phylogenetic distribution from predominantly group B2 to predominantly groups A
      and B1. Associations of bacterial traits with clinical factors varied
      considerably, depending on subgroup and statistical method. However, certain
      putative virulence genes (including several "nontraditional" markers, such as
      pathogenicity island-associated malX) repeatedly emerged as significant
      epidemiological predictors, which provided evidence of their possible relevance
      in host-pathogen interactions and hence as potential targets for preventive
      interventions against extraintestinal infections due to E. coli.

PMID- 11992280
TI  - The changing age and seasonal profile of pertussis in Canada.
AB  - During the postvaccine era in Canada, most cases of pertussis have been reported
      in children <5 years of age, with the highest incidence, morbidity, and mortality
      in infants <1 year old. Population-based data, with very high laboratory
      confirmation rates and hospital separation and mortality statistics, chronicle
      the changing age and seasonal profile associated with pertussis over recent
      successive outbreaks in British Columbia, Canada. A large outbreak during 2000
      highlights 2 important changes to the postvaccine profile. For the first time in
      Canada, the incidence of pertussis among preteens and teens surpassed that of all
      other age groups. At the same time, a decreasing incidence of pertussis among
      infants and preschool children highlights reduced susceptibility in the very
      young. Recent changes in the childhood immunization program (including
      introduction of an acellular pertussis vaccine), waning immunity, and changes in
      laboratory methods are considered in explaining these 2 simultaneous but
      divergent trends in the pertussis profile.

PMID- 11992281
TI  - Multilocus restriction typing: a novel tool for studying global epidemiology of
      Burkholderia cepacia complex infection in cystic fibrosis.
AB  - Burkholderia cepacia complex infections contribute significantly to mortality and
      morbidity in persons with cystic fibrosis (CF). The aim of this study was to
      evaluate the use of a novel typing method, multilocus restriction typing (MLRT),
      for investigation of the global epidemiology of B. cepacia complex genomovar III,
      the species most commonly encountered in CF. In the MLRT method, variation at
      several loci is indexed by restriction analysis of polymerase chain reaction
      amplified genes. Data obtained by MLRT and pulsed-field gel electrophoresis
      analysis of a large number of B. cepacia genomovar III isolates (including
      isolates belonging to epidemic lineages and environmental isolates) show a strong
      correlation. MLRT extends the utility of isolate genotyping by allowing
      comparisons of isolates collected in studies of larger scale (both temporal and
      spatial). The portability of MLRT data will facilitate comparison of data
      obtained in different laboratories. In addition, data obtained with MLRT can be
      used in studies of bacterial population structure.

PMID- 11992282
TI  - Association between Helicobacter felis-induced gastritis and elevated glycated
      hemoglobin levels in a mouse model of type 1 diabetes.
AB  - Helicobacter pylori infection has been described in association with increases in
      glycated hemoglobin (HbA(1c)) levels in patients with type 1 diabetes. The
      purpose of the present study was to use an animal model of Helicobacter infection
      to test, under controlled conditions, the hypothesis that infection is associated
      with high HbA(1c) levels. Diabetes was induced in C57BL/6 mice by administration
      of streptozotocin, and the mice were orally inoculated with H. felis. Six weeks
      after inoculation, infected mice (n=10) showed gastritis scores significantly
      greater (P=.01) than those of uninfected mice (n=10). HbA(1c) levels were
      significantly higher in infected mice with gastritis (11.6%; n=6) than in
      infected mice without gastritis (8.4%; n=4) or uninfected mice (7.6%; n=10). It
      was concluded that gastritis induced by H. felis is associated with increased
      HbA(1c) levels in the mouse model of streptozotocin-induced diabetes.

PMID- 11992283
TI  - Clinical and genetic heterogeneity of inherited autosomal recessive
      susceptibility to disseminated Mycobacterium bovis bacille calmette-guerin
      infection.
AB  - Five patients from 4 unrelated Tunisian families who presented with disseminated
      neonatal infection by Mycobacterium bovis bacille Calmette-Guerin strain were
      investigated. Two unrelated patients had different homozygous interleukin-12
      receptor beta1 subunit gene splice-site mutations (64+5G-->A and 550-2A-->G). Two
      siblings and 1 unrelated patient, all of whom were from the same town, carried
      the same mutation (297del8) within the interleukin-12p40 gene. This is the first
      description of familial cytokine deficiency reported so far. All patients had
      complete lack of expression of the affected polypeptide and a profound deficiency
      of in vitro interferon-gamma production. The clinical severity of the
      mycobacterial infection was heterogeneous, even among affected members of the
      same family, which suggests the intervention of modifying genes.

PMID- 11992284
TI  - The granulocyte colony-stimulating factor response after intrapulmonary and
      systemic bacterial challenges.
AB  - In contrast to many cytokines such as tumor necrosis factor (TNF)-alpha, we
      hypothesized that, after an intrapulmonary bacterial challenge, lung-derived
      granulocyte colony-stimulating factor (G-CSF) would subsequently enter the
      systemic circulation. BALB/c mice were given Escherichia coli or saline, either
      intratracheally or intravenously. Four hours after intratracheal E. coli
      administration, bronchoalveolar lavage fluid (BALF) and plasma G-CSF
      concentrations increased, compared with concentrations in phosphate-buffered
      saline-treated controls. Lung G-CSF messenger RNA (mRNA) increased to 586+/-229
      copies G-CSF mRNA/ng ribosomal RNA (rRNA) from the values in control animals
      (<0.5 copies/ng rRNA). In contrast, G-CSF mRNA was not increased in the
      extrapulmonary tissues examined (liver, spleen, and kidney) in mice challenged
      with intratracheal E. coli (<1 copy/ng rRNA). Intravenous E. coli increased
      plasma G-CSF and TNF-alpha, but neither cytokine was detected in BALF. These data
      show that, after an intrapulmonary infection, both lung and circulating G-CSF
      increase and that the lung is the likely source.

PMID- 11992285
TI  - The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against
      disseminated candidiasis.
AB  - Toll-like receptors (TLRs) represent the main class of pattern-recognition
      receptors involved in sensing pathogenic microorganisms. The aim of the present
      study was to assess the role of TLR4 in the defense against Candida albicans
      infection. The outgrowth of C. albicans was 10-fold higher in TLR4-defective
      C3H/HeJ mice, compared with that in control C3H/HeN mice (P<.05). Production of
      tumor necrosis factor (TNF) and interleukin (IL)-1alpha and IL-1beta by mouse
      macrophages in response to C. albicans stimulation was not affected by TLR4, and
      the candidacidal capacities of the neutrophils and macrophages of C3H/HeJ mice
      were normal. In contrast, production of the CXC chemokines KC and macrophage
      inhibitory protein-2 was 40%-60% lower by the macrophages of C3H/HeJ mice
      (P<.05), which resulted in a 40% decrease in neutrophil recruitment to the site
      of infection. Candida-induced TNF and IL-1beta production by human peripheral
      blood mononuclear cells was significantly inhibited by blocking anti-TLR2
      antibodies in vitro. In conclusion, TLR4-defective C3H/HeJ mice are more
      susceptible to C. albicans infection, and this is associated with impaired
      chemokine expression and neutrophil recruitment.

PMID- 11992286
TI  - Therapeutic use of cytokines to modulate phagocyte function for the treatment of
      infectious diseases: current status of granulocyte colony-stimulating factor,
      granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating
      factor, and interferon-gamma.
AB  - The innate immune system represents the initial arm of host defense against
      pathogenic bacteria, fungi, and parasites. Neutrophils, monocytes, and tissue
      based macrophages are major cellular components of this system. The potential
      ability to augment activity of the innate immune system has increased
      dramatically during the past 2 decades, with the discovery and development of
      cytokines. Four cytokines, namely granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony
      stimulating factor (M-CSF), and interferon (IFN)-gamma, have received increasing
      attention as potential adjunctive agents for the treatment of infectious
      diseases. In various animal models of infection, therapeutic administration of
      each of the 4 cytokines has been shown to enhance pathogen eradication and to
      decrease morbidity and/or mortality. However, variable therapeutic efficacy has
      been reported in clinical trials conducted to date. This review summarizes the
      current status of the use of G-CSF, GM-CSF, M-CSF, and IFN-gamma in the treatment
      of infectious diseases.

PMID- 11992287
TI  - Outbreaks of adult gastroenteritis traced to a single genotype of rotavirus.
AB  - Between November 1998 and December 2000, the Centers for Disease Control and
      Prevention screened samples from 263 outbreaks of gastroenteritis in the United
      States and identified 3 that were associated with rotavirus among adults.
      Rotaviruses from each outbreak were further characterized by reverse
      transcription polymerase chain reaction. Surprisingly, all specimens were of
      serotype G2, a strain that is, as determined by high-stringency hybridization
      analysis, genetically distinct in all 11 gene segments from the other common
      rotavirus strains in circulation. The unusual coincidence of identification of
      only G2 strains in these 3 outbreaks of rotavirus gastroenteritis among adults is
      similar to results from other studies, in which G2 strains were found in
      association with more-severe disease in children than other rotavirus serotypes
      and in association with outbreaks of diarrhea among adults in Japan. Although
      rotavirus infections in adults are relatively uncommon, which indicates that good
      overall protective immunity exists, the predominance of G2 strains in outbreaks
      that have occurred in adults suggests that natural immunity to more common
      strains does not always provide adequate heterotypic immunity to G2 strains. For
      the rotavirus vaccines under development, special attention may need to be paid
      to protection against G2 strains.

PMID- 11992288
TI  - Evolution of human immunodeficiency virus type 1 populations after resumption of
      therapy following treatment interruption and shift in resistance genotype.
AB  - Conventional genotyping of human immunodeficiency virus type 1 often reveals a
      shift from a drug-resistant genotype to a wild-type genotype after treatment
      interruption. A real-time polymerase chain reaction-based technique was used to
      detect minority resistant populations in 13 patients who showed genotype
      reversion after interruption of treatment for 3 months. Sixty-two percent of
      patients in whom the V82A and L90M protease mutations were no longer detectable
      by conventional genotyping still harbored minority resistant variants, in
      proportions ranging from 0.1% to 21%. None of the patients with these minority
      resistant variants who received a protease-inhibitor regimen on resumption of
      therapy had a response to treatment. However, population sequencing and clonal
      analysis of plasma samples obtained 1-2 months after resumption of treatment
      revealed the presence of wild-type virus during the initial decline in plasma
      virus load, which indicates that minority resistant variants were not rapidly
      selected.

PMID- 11992289
TI  - Clonal association of Staphylococcus aureus causing bullous impetigo and the
      emergence of new methicillin-resistant clonal groups in Kansai district in Japan.
AB  - A molecular epidemiological analysis was performed to reveal the clonal
      association of Staphylococcus aureus strains isolated from patients with bullous
      impetigo. Pulsed-field gel electrophoresis with cluster analysis, genetic and
      phenotypic characterizations, and antimicrobial susceptibility profiling of 88 S.
      aureus strains isolated from outpatients at 4 hospitals in the Kansai district in
      Japan were undertaken. Three distinct clonal groups were identified: 2 of them
      carried the exfoliative toxin (ET) A gene (eta), and the other carried the ETB
      gene (etb). The former groups represent 2 eta-positive clonal groups that have
      not been described previously. All the strains in the more dominant eta-positive
      clonal group and some of the strains in the etb-positive clonal group were
      methicillin-resistant S. aureus (MRSA) showing borderline-to-moderate resistance
      to beta-lactams. These MRSA strains appear to be emerging clonal groups that have
      not been considered in previous epidemiological studies of ET-producing S. aureus
      in Japan and thus pose a significant threat for future treatment of patients with
      bullous impetigo and/or staphylococcal scalded-skin syndrome.

PMID- 11992290
TI  - Variant mannose-binding lectin alleles are not associated with susceptibility to
      or outcome of invasive pneumococcal infection in randomly included patients.
AB  - Invasive pneumococcal disease is a serious infection that primarily affects very
      young children and elderly or immunocompromised individuals but also affects
      previously healthy people. Variant mannose-binding lectin (MBL) alleles are
      associated with recurrent infections and may be a risk factor for pneumococcal
      infections. To assess the influence of MBL genotypes on the course and outcome of
      invasive pneumococcal disease, clinical data for 141 adult patients were
      collected prospectively and their genotypes were determined. All patients
      included had positive blood cultures for Streptococcus pneumoniae. The
      distribution of variant MBL alleles related to low MBL serum concentrations was
      similar among the patients and healthy individuals, and MBL genotype was not
      associated with infection outcome. Thus, in a random adult population with
      invasive pneumococcal infection, MBL does not seem to play a role in the
      pathophysiology, in contrast to earlier observations in patients with other
      concomitant immune abnormalities.

PMID- 11992291
TI  - Molecular epidemiology of 3 putative virulence genes for Escherichia coli urinary
      tract infection-usp, iha, and iroN(E. coli).
AB  - This study describes the epidemiological association of 3 putative genes for
      virulence of uropathogenic Escherichia coli; uropathogenic specific protein
      (usp), a Vibrio cholerae zot gene homologue; IrgA homologue adhesin (iha), a
      nonhemagglutinating adhesin; and iroN(E. coli), a catechole siderophore receptor
      homologue. We compared the relative frequency in urinary tract infection (UTI)
      isolates (n=508), compared with non-UTI isolates (n=416). iroN(E. coli) occurred
      2.1-3.6 times more frequently in UTI isolates than in rectal isolates (P=1.1x10
      18 to P=2.7x10-5) and was associated with several uropathogenic virulence genes
      found on pathogenicity islands. usp occurred more frequently in isolates from
      patients with pyelonephritis (P=3.6x10-9), in periurethral isolates (P=.001), and
      in isolates from patients with UTI who were aged 40-65 years (P=.004), when
      compared with the rectal isolates; iha was not associated with UTI in this study.

PMID- 11992292
TI  - Gonococcal cervicitis is associated with reduced systemic CD8+ T cell responses
      in human immunodeficiency virus type 1-infected and exposed, uninfected sex
      workers.
AB  - Neisseria gonorrhoeae cervicitis and human immunodeficiency virus (HIV) type 1
      frequently coinfect core transmitter populations, such as female sex workers.
      Gonococcal cervicitis is associated with increased viral shedding and plasma
      viremia in HIV-1-infected women and increased HIV-1 susceptibility in uninfected
      women. We studied the influence of gonococcal cervicitis on CD8(+) interferon
      (IFN)-gamma responses to HIV-1 and cytomegalovirus (CMV) epitopes in HIV-1
      infected and in highly-exposed, persistently seronegative (HEPS) female sex
      workers. In HIV-1-infected women, gonococcal cervicitis was associated with
      reduced IFN-gamma responses in bulk CD8(+) lymphocyte populations, and
      intracellular cytokine staining, combined with class I major histocompatibility
      complex (MHC)-peptide tetramer studies, demonstrated reduced IFN-gamma production
      by HIV-1 epitope-specific CD8(+) lymphocytes. In HEPS sex workers, cervicitis was
      associated with the transient loss of systemic HIV-1-specific CD8(+) responses
      and with reduced function of CMV-specific CD8(+) lymphocytes. Impaired function
      of virus-specific CD8(+) lymphocytes may partly explain the deleterious effects
      of gonococcal cervicitis on HIV-1 immune control and susceptibility.

PMID- 11992293
TI  - Mutations in the dihydropteroate synthase gene of human-derived Pneumocystis
      carinii isolates from Italy are infrequent but correlate with prior sulfa
      prophylaxis.
AB  - Mutations in the human-derived Pneumocystis carinii dihydropteroate synthase
      (DHPS) gene have been reported with increasing frequency and have been linked to
      prior sulfa prophylaxis and possible emergence of sulfa resistance. This study
      was done to examine the prevalence and clinical significance of P. carinii DHPS
      mutations in Italian patients. A previously described single-strand conformation
      polymorphism technique was used to identify P. carinii DHPS mutations in 107
      patients with acquired immunodeficiency syndrome. Overall prevalence (8%) was low
      compared with that in other reports. Mutations were observed in 19% (6/31) of
      patients exposed to sulfa prophylaxis, compared with 4% (3/76) of patients not
      exposed to sulfa prophylaxis (P=.017). No significant association was observed
      between the presence of DHPS mutations and mortality, CD4 cell count, or
      demographic factors. The study confirms the association between DHPS mutations
      and prior sulfa prophylaxis and shows that the prevalence of DHPS mutations in an
      Italian patient population is lower than that in other populations.

PMID- 11992294
TI  - Relapses versus reinfections in patients coinfected with Leishmania infantum and
      human immunodeficiency virus type 1.
AB  - In the Mediterranean basin, Leishmania infantum is a major opportunistic parasite
      in people with acquired immunodeficiency syndrome (AIDS), and up to 9% of the
      patients with AIDS suffer from newly acquired or reactivated visceral
      leishmaniasis. Distinguishing between reinfections and relapses in these patients
      is important because some apparent treatment failures occur in patients with new
      rather than reactivated infections. Isoenzyme characterization is limited for use
      in determining relapsed versus newly acquired leishmaniasis in human
      immunodeficiency virus (HIV)-infected patients because of the variability of L.
      infantum and the predominance of the MON-1 zymodeme in people coinfected with
      HIV. A seminested polymerase chain reaction (PCR) was used to amplify L. infantum
      minicircle kinetoplast DNA, and, after digestion, the restriction fragment-length
      polymorphism (RFLP) profiles showed that 3 (7.5%) of 40 patients coinfected with
      L. infantum and HIV had a new infection, whereas isoenzyme characterization
      indicated that all 40 patients had infection relapses. These results suggest the
      utility of this PCR-RFLP analysis in detecting leishmaniasis reinfection in HIV
      positive patients.

PMID- 11992295
TI  - Central role of the spleen in malaria parasite clearance.
AB  - In acute malaria, red blood cells (RBCs) that have been parasitized, but no
      longer contain a malaria parasite, are found in the circulation (ring-infected
      erythrocyte surface antigen [RESA]-RBCs). These are thought to arise by splenic
      removal of dead or damaged intraerythrocytic parasites and return of the intact
      RBCs to the circulation. In a study of 5 patients with acute falciparum malaria
      who had previously undergone splenectomy, it was found that none of these 5
      patients had any circulating RESA-RBCs, in contrast to the uniform finding of
      RESA-RBCs in all patients with acute malaria and intact spleens. Parasite
      clearance after artesunate treatment was markedly prolonged, although the
      parasites appeared to be dead and could not be cultured ex vivo. These
      observations confirm the central role of the spleen in the clearance of
      parasitized RBCs after antimalarial treatment with an artemisinin derivative.
      Current criteria for high-grade antimalarial drug resistance that are based on
      changes in parasitemia are not appropriate for asplenic patients.

PMID- 11992296
TI  - Carriage of antibiotic-resistant fecal bacteria in Nepal.

PMID- 11992299
TI  - Interventions that increase use of adult immunization and cancer screening
      services: a meta-analysis.
AB  - PURPOSE: The relative effectiveness of the diverse approaches used to promote
      preventive care activities, such as cancer screening and adult immunization, is
      unknown. Despite many high-quality published studies, practices and policymakers
      attempting to improve preventive care have little definitive information on which
      to base decisions. Thus, we quantitatively assessed the relative effectiveness of
      previously studied approaches for improving adherence to adult immunization and
      cancer screening guidelines. DATA SOURCES: MEDLINE, the Cochrane Effective
      Practice and Organization of Care Review Group register, previous systematic
      reviews, and the Medicare Health Care Quality Improvement Project database. STUDY
      SELECTION: Controlled clinical trials that assessed interventions to increase use
      of immunizations for influenza and pneumococcal pneumonia and screening for
      colon, breast, and cervical cancer in adults. DATA EXTRACTION: Two reviewers
      independently extracted data on characteristics and outcomes from unmasked
      articles. Intervention components to increase use of services were classified as
      reminder, feedback, education, financial incentive, legislative action,
      organizational change, or mass media campaign. DATA SYNTHESIS: Of 552 abstracts
      and articles, 108 met the inclusion criteria. To assess the effect of
      intervention components, meta-regression models were developed for immunizations
      and each cancer screening service by using 81 studies with a usual care or
      control group. The most potent intervention types involved organizational change
      (the adjusted odds ratios for increased use of services from organizational
      change ranged from 2.47 to 17.6). Organizational change interventions included
      the use of separate clinics devoted to prevention, use of a planned care visit
      for prevention, or designation of nonphysician staff to do specific prevention
      activities. The next most effective intervention components were patient
      financial incentives (adjusted odds ratios, 1.82 to 3.42) and patient reminders
      (adjusted odds ratios, 1.74 to 2.75); the adjusted odds ratios ranged from 1.29
      to 1.53 for patient education and from 1.10 to 1.76 for feedback. CONCLUSIONS:
      Rates of adult immunization and cancer screening are most likely to improve when
      a health care organization supports performance of these activities through
      organizational changes in staffing and clinical procedures. Involving patients in
      self-management through patient financial incentives and reminders is also likely
      to positively affect performance.

PMID- 11992300
TI  - Public expectations and attitudes for annual physical examinations and testing.
AB  - BACKGROUND: Recent guidelines for adult prevention do not recommend a
      comprehensive annual physical examination, but current public expectations in
      light of this change are unknown. OBJECTIVE: To determine public belief in the
      need for and content of an annual physical examination and to examine the effect
      of financial charges on these beliefs. DESIGN: Telephone survey. SETTING: Three
      U.S. cities. PARTICIPANTS: Adult English-speaking respondents. MEASUREMENTS:
      Percentage of respondents answering that an annual physical examination is
      necessary and percentage desiring individual components of the history, physical
      examination, and laboratory testing, with and without knowledge of charges.
      RESULTS: Of 1203 respondents, 66% (67% in Denver, Colorado; 71% in Boston,
      Massachusetts; and 58% in San Diego, California) believed that in addition to
      regular care, an annual physical examination is necessary. Among the 600
      respondents presented with charge information, interest decreased from 63% to 33%
      if payment were required. For history, greater than 90% believed that diet,
      exercise, and tobacco and alcohol use should be discussed, while 60% believed
      that seatbelt use and sexual history should be discussed. For the physical
      examination, greater than 90% felt that blood pressure should be measured and
      that the heart and lungs, abdomen, reflexes, and prostate should be examined.
      However, fewer than 80% thought that hearing and vision should be tested. Many
      tests, including the Papanicolaou smear (75%), mammography (71%), cholesterol
      measurement (65%), prostate-specific antigen test (65%), urinalysis (40%), blood
      glucose measurement (41%), fecal occult blood testing (39%), and chest
      radiography (36%), were desired. Interest in these tests decreased substantially
      when the charges were known. CONCLUSION: Public desire for a comprehensive annual
      physical examination is high across the United States and is sensitive to
      charges.

PMID- 11992301
TI  - Serologic immunity to diphtheria and tetanus in the United States.
AB  - BACKGROUND: Serologic data on diseases that are preventable by vaccine are useful
      to evaluate the success of immunization programs and to identify susceptible
      subgroups. OBJECTIVE: To provide national estimates of immunity to diphtheria and
      tetanus by measurement of serum antibody levels. DESIGN: Examination of data from
      the Third National Health and Nutrition Examination Survey, a representative
      cross-sectional sample of the U.S. population. SETTING: 89 randomly selected
      locations throughout the United States. PARTICIPANTS: 18 045 persons 6 years of
      age or older who were examined from 1988 to 1994. MEASUREMENTS: Serum samples
      obtained at a single time point were tested for diphtheria and tetanus antitoxin.
      RESULTS: Overall, 60.5% of Americans 6 years of age or older had fully protective
      levels of diphtheria antibody (> or =0.10 IU/mL) and 72.3% had protective levels
      of tetanus antibody (> 0.15 IU/mL). Ninety-one percent of Americans 6 to 11 years
      of age had protective levels of both diphtheria and tetanus antibody; this
      proportion decreased to approximately 30% among persons 70 years of age (29.5%
      for diphtheria and 31.0% for tetanus). Adult Mexican-Americans were slightly less
      likely to have protective levels of antibody to both toxins. Only 47% of persons
      20 years of age or older had levels that were protective against both diseases,
      and only 63% of adults who were protected against tetanus were also protected
      against diphtheria. CONCLUSIONS: A substantial proportion of adults in the United
      States do not have antibody levels that are protective against diphtheria and
      tetanus. In addition, although the recommended vaccine is a combination of
      tetanus and diphtheria, only 63% of adults with protective antibody to tetanus
      also had protective antibody to diphtheria.

PMID- 11992302
TI  - Reversibility of cirrhosis in patients cured of thalassemia by bone marrow
      transplantation.
AB  - BACKGROUND: Cirrhosis is a well-known complication of thalassemia major. In this
      context, it is a consequence of iron overload and hepatitis C virus infection and
      generally seems to be irreversible. OBJECTIVE: To determine whether cirrhosis in
      thalassemia major can be reversible. DESIGN: Retrospective study. SETTING: Bone
      Marrow Transplantation Unit and Pathology Service, Pesaro Hospital, Pesaro,
      Italy. PATIENTS: 6 patients who developed liver cirrhosis before or after their
      thalassemia was cured by bone marrow transplantation (age at transplantation, 11
      to 25 years). After diagnosis of cirrhosis, the patients received iron depletion
      and antiviral therapies. MEASUREMENTS: Each liver biopsy specimen was coded. A
      liver pathologist and a member of the transplantation center with expertise in
      hepatopathology graded the specimens by using the Ishak staging and grading
      systems. Neither knew the patient's identity or the sequence of biopsy with
      regard to the time of treatment. RESULTS: After the patients received iron
      depletion and antiviral therapies, liver biopsy specimens showed impressive
      reduction in liver iron stores. In 4 patients, iron removal was complete. Serum
      aminotransferase levels decreased in all patients and normalized in 5; histologic
      inflammatory activity decreased in all patients and disappeared in 2. Follow-up
      biopsies showed regression of incomplete or definite cirrhosis in all patients; 3
      patients had presented with portal fibrosis without bridging, and the others had
      portal fibrosis and portal-to-portal bridging. Several biopsies and the presence
      of many portal spaces confirmed the diagnosis of cirrhosis; follow-up biopsies
      confirmed regression of cirrhosis. CONCLUSION: In some patients in whom bone
      marrow transplantation has cured thalassemia, cirrhosis may be reversible after
      iron removal treatment.

PMID- 11992303
TI  - Strategies for culturally effective end-of-life care.
AB  - As a result of profound worldwide demographic change, physicians will
      increasingly care for patients from cultural backgrounds other than their own.
      Differences in beliefs, values, and traditional health care practices are of
      particular relevance at the end of life. Health care providers and patients and
      families may not have shared understandings of the meaning of illness or death
      and may not agree on the best strategies to plan for the end of life or to
      alleviate pain and suffering. Good end-of-life care may be complicated by
      disagreements between physicians and patients, difficult interactions, or
      decisions the physician does not understand. Challenges may result from cultural
      differences between the patient's background and traditional medical practice.
      Values so ingrained in physicians as to be unquestioned may be alien to patients
      from different backgrounds. Physicians need to be sensitive to cultural
      differences and to develop the skills necessary to work with patients from
      diverse backgrounds. Community and cultural ties provide a source of great
      comfort as patients and families prepare for death. This paper describes two
      cases that raise issues about cross-cultural end-of-life practice and suggests
      strategies for negotiating common problems. Physicians should assess the cultural
      background of each patient and inquire about values that may affect care at the
      end of life. They should become aware of the specific beliefs and practices of
      the populations they serve, always remembering to inquire whether an individual
      patient adheres to these cultural beliefs. Attention to cultural difference
      enables the physician to provide comprehensive and compassionate palliative care
      at the end of life.

PMID- 11992304
TI  - Postmenopausal estrogen replacement and risk for venous thromboembolism: a
      systematic review and meta-analysis for the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Postmenopausal estrogen replacement is widely used in the United
      States but poses important health risks. PURPOSE: To assess the risk for venous
      thromboembolism with postmenopausal estrogen replacement by using literature
      review and meta-analysis. DATA SOURCES: All relevant English-language studies
      identified in searches of the MEDLINE (1966 to December 2000), HealthSTAR (1975
      to December 2000), and Cochrane Library databases, and references lists of key
      articles. STUDY SELECTION: All published studies of postmenopausal estrogen
      replacement reporting venous thromboembolism as an outcome or adverse event. DATA
      EXTRACTION: 12 studies of estrogen were identified (3 randomized, controlled
      trials; 8 case-control studies; and 1 cohort study). Data were extracted on
      participants, interventions, event rates, and confounders. Two reviewers
      independently rated study quality on the basis of established criteria. DATA
      SYNTHESIS: A Bayesian meta-analysis was conducted. When data from all studies
      were pooled, current estrogen use was associated with an increased risk for
      venous thromboembolism (relative risk, 2.14 [95% credible interval, 1.64 to
      2.81]). Estimates did not significantly change when studies were pooled according
      to study design, quality score, or whether participants had preexisting coronary
      artery disease. The absolute rate increase was 1.5 venous thromboembolic events
      per 10 000 women in 1 year. Six case-control studies that reported risk according
      to duration of use found that risk was highest in the first year of use (relative
      risk, 3.49 [credible interval, 2.33 to 5.59]). CONCLUSION: Postmenopausal
      estrogen replacement is associated with an increased risk for venous
      thromboembolism, and this risk may be highest in the first year of use.

PMID- 11992305
TI  - Echocardiography in the management of pulmonary embolism.
AB  - Echocardiography is not recommended as a routine imaging test to diagnose
      suspected pulmonary embolism. However, it is useful for identifying patients with
      pulmonary embolism who may have a poor prognosis. It can be used for rapid and
      accurate risk assessment. Moderate or severe right ventricular hypokinesis,
      persistent pulmonary hypertension, a patent foramen ovale, and free-floating
      right-heart thrombus are echocardiographic markers that identify patients at risk
      for death or recurrent thromboembolism. Such patients warrant consideration for
      thrombolysis or embolectomy. Serial imaging of right ventricular function can
      help physicians monitor the effect of treatment and judge whether the selected
      management strategy is successful. Further research will clarify and define more
      precisely the utility and limitations of echocardiography in the management of
      pulmonary embolism.

PMID- 11992306
TI  - The annual physical examination: needless ritual or necessary routine?

PMID- 11992307
TI  - Medical ground zero: an early experience of the world trade center disaster.

PMID- 11992309
TI  - Principles of appropriate antibiotic use: acute pharyngitis.

PMID- 11992310
TI  - Principles of judicious antibiotic use: acute rhinosinusitis.

PMID- 11992311
TI  - Physicians and joint negotiations.

PMID- 11992313
TI  - Principles of judicious antibiotic use: nonspecific upper respiratory tract
      infections.

PMID- 11992318
TI  - Thalidomide and venous thrombosis.

PMID- 11992319
TI  - Summaries for patients. Ways to deliver preventive health care.

PMID- 11992320
TI  - Summaries for patients. Public expectations for annual physical examination and
      testing.

PMID- 11992321
TI  - Summaries for patients. Immunity to diphtheria and tetanus in the United States.

PMID- 11992322
TI  - Summaries for patients. Reversibility of liver scarring in patients who are cured
      of thalassemia.

PMID- 11992323
TI  - Summaries for patients. Postmenopausal estrogen replacement therapy and the risk
      for blood clots: a review from the U.S. Preventive Services Task Force.

PMID- 11992324
TI  - [Depth psychologically founded psychotherapy].
AB  - Depth psychologically founded psychotherapy is a treatment based on
      psychoanalysis. This article describes the treatment method. The following
      aspects are emphasized: Terminology definitions, historical development, specific
      differences between depth psychologically founded and analytic psychotherapy as
      well as the treatment practice with the focus on current psychosocial conflicts
      and their implications. Indication, counter-indication and differential
      indication are also discussed, and the status of empirical evaluation is
      described. Finally, the therapist's qualifications for this treatment method are
      elucidated.

PMID- 11992325
TI  - [The effectiveness of psychodynamic therapy. A review using criteria of evidence
      based medicine].
AB  - The existing studies on the effectiveness of psychodynamic therapy are reviewed.
      All studies published between 1960 and 2001 were collected. In the first part of
      this survey, the focus is on short-term psychodynamic therapy, the second part
      focuses on longer-term psychoanalytic and psychodynamic therapy. The studies are
      reviewed with regard to forms of disorders. The methodological quality of the
      studies is judged according to criteria of evidence-based medicine. These
      criteria themselves are also critically discussed. Although they vary concerning
      their methodological quality, the studies reveal evidence of the effectiveness of
      both short-term and long-term psychodynamic therapy. In a meta-analytic
      evaluation performed by the author, substantial effects were found for
      psychodynamic therapy of personality disorders, i.e. 1.13 (self-report measures)
      and 1.57 (observer-rated measures) for short-term psychodynamic therapy and 1.05
      (self-report measures) and 2.11 (observer-rated measures) for longer term
      psychodynamic therapy. Although there is evidence of the effectiveness of
      psychodynamic therapy, further research of specific forms of psychodynamic
      therapy in specific disorders is necessary.

PMID- 11992326
TI  - [Gaining insight and structural capability as goals of psychodynamic
      psychotherapy].
AB  - Psychodynamic psychotherapy in the sense of German psychotherapy guidelines is
      currently the most frequently used treatment in outpatient psychotherapy. This
      report summarizes the psychodynamic fundaments of this method and distinguishes
      the conflict exposure and the structure formation as significant therapeutic
      aims. The subject of personality structure is dealt with according to the OPD
      (operationalized psychodynamic diagnosis) system which allows an
      operationalization and empirical investigation of structural aspects. The
      treatment techniques used to achieve structure-related therapy aims (e.g. the
      ability to differentiate affects, impulse control, empathy, emotional expression,
      attachment, separation, etc.) are described in detail.

PMID- 11992327
TI  - [Prevalence and effects of depressive and anxiety symptoms in internal medicine
      inpatients during the first year after hospital discharge].
AB  - In a prospective follow-up study the German version of the Hospital Anxiety and
      Depression Scale (HADS) was used to determine the prevalence of anxiety and
      depressive symptoms in internal medicine inpatients. From a total cohort of 376
      admitted study patients questionnaires were completed at admission and after one
      year follow-up. The data demonstrated that the mean HADS score on the anxiety
      subscale decreased significantly from 6.7 3.5 at study inclusion to 5.8 3.8 after
      one year (p < 0.0005) while the mean HADS score on the depression subscale was
      relatively stable (5.3 3.6 versus 5.4 4.3, p = n.s.). Odds ratios for the
      prediction of positive HADS results at follow-up were 4.1 (95%-CI 2.0-8.4) for
      anxiety symptoms and 8.2 (95%-CI 4.6-14.6) for depressive symptoms. Patients with
      abnormal HADS anxiety scores were significantly more frequently rehospitalized
      (Odds ratio 1.9; p = 0.028) and also more frequently reported pain symptoms (Odds
      ratio 2.0; p = 0.019). These results demonstrate the persistence of depressive
      symptoms and the frequent utilization of health care in internal medicine
      inpatients with psychiatric disorders in the first year after hospital discharge.

PMID- 11992328
TI  - [The current conception of the unconscious - empirical results of neurobiology,
      cognitive sciences, social psychology and emotion research].
AB  - The influence of the unconscious on psychosomatic medicine and psychotherapy: a
      comprehensive concept of unconscious processes based on empirical evidence. The
      theory of the Unconscious constitutes the basis of psychoanalysis and of
      psychodynamic therapy. The traditional description of the Unconscious as given by
      Freud is of historical significance and not only gained widespread acceptance but
      also attracted much criticism. The most important findings of neurobiology, the
      cognitive sciences, social psychology and emotion research in relation to the
      Unconscious are compared with this traditional definition. Empirical observations
      on defence mechanisms are of particular interest in this context. A comprehensive
      concept of unconscious processes is revealed: the fundamental process of brain
      function is unconscious. Parts of the symbolic-declarative and emotional
      procedural processing by the brain are permanently unconscious. Other parts of
      these processing procedures are conscious or can be brought to the conscious or
      alternatively, can also be excluded from the conscious. Unconscious processes
      exert decisive influence on experience and behaviour; for this reason, every form
      of psychotherapy should take into account such unconscious processes.

PMID- 11992329
TI  - Parenteral analgesic and sedative use among ED patients in the United States:
      combined results from the National Hospital Ambulatory Medical Care Survey
      (NHAMCS) 1992-1997.
AB  - This article describes parenteral analgesic and sedative (PAS) use among patients
      treated in US emergency departments (EDs). Data representing 6 consecutive years
      (1992-1997) from the National Hospital Ambulatory Medical Care Survey (NHAMCS)
      were combined and analyzed. Patients were identified as having received PAS if
      they received fentanyl, ketamine, meperidine, methohexital, midazolam, morphine,
      nitrous oxide, or propofol. Patients were stratified according to age (pediatric
      <18 yrs), race, sex, insurance, type of hospital, urgency of visit, and ICD-9
      (International Classification of Diseases, 9th revision) diagnostic codes.
      Logistic regression was performed to determine independent associations and
      calculate odds ratios (OR) for receiving analgesia or sedation. A total of 43,725
      pediatric and 114,207 adult ED encounters were analyzed and represented a
      weighted sample of 555.3 million ED visits. For patients with orthopedic
      fractures, African-American children covered by Medicaid insurance were the least
      likely to receive PAS (OR 0.2, 95% confidence interval [CI] 0.1-0.6). These
      results suggest that variations may be occurring among ED patients receiving PAS.

PMID- 11992330
TI  - Outcomes of referrals to the ED by family physicians.
AB  - Patients are commonly referred to the emergency department (ED) by family
      physicians (FPs). This study was undertaken to determine the outcome of these
      referred patients. A prospective cohort study of 196 patients referred by FPs to
      the ED of an urban, tertiary referral center was performed. Key outcome measures
      were the rate at which investigations or interventions were performed,
      consultation and admission rates, and the percentage of referrals that were
      appropriate. Comparison was made with a random cohort of non-referred patients.
      Information was collected from a questionnaire completed by the emergency
      physician and by chart review. Eighty-six percent of patients referred to the ED
      had some sort of investigation or intervention performed, which was significantly
      higher than the 66.7% rate in non-referred patients (P <.001). Twenty-nine
      percent of referred patients received a consultation in the ED compared with
      16.4% of non-referred patients (P <.01), and 16.0% were admitted to hospital
      compared with 10.0% in the non-referred group (P <.10). By using the process of
      care method, 75.5% of referrals by FPs to the ED were appropriate. Family
      physicians are quite selective in their referrals to the ED. There is a high rate
      of admission and specialist consultation for referred patients. The vast majority
      of patients who are referred receive at least 1 investigation or intervention in
      the ED, and most referrals are appropriate.

PMID- 11992331
TI  - Gender differences in narcotic-induced emesis in the ED.
AB  - Narcotic analgesia is commonly given in the emergency department. Narcotic
      induced nausea and vomiting is thought to be a common occurrence, but the gender
      incidence and associations are not well defined. The aim of this study was to
      document the sex-related complication of nausea and vomiting after opiate
      administration for pain relief in the ED. The study hypothesis was that men and
      women have the same rate of narcotic-induced emesis in the ED. A prospective,
      convenience study of the use of narcotic analgesic on patients in an innercity
      Level I Trauma Center was undertaken. Information concerning the reason for
      narcotics, complications, number of doses, and route of administration were
      studied. The emergency physicians were allowed clinical judgment to treat the
      patients with any narcotic agent in any dose increment. The data were entered
      into an SPSS program (Chicago, IL). Analysis between groups (men v women) was
      then conducted by an independent t test. We compared the 2 groups across 6
      categories: cause of injury, presenting pain scale, first drug given, first dose
      given, first route of drug, and requires an anti-emetic. A Bonferroni procedure
      was used to correct for the higher probability of significant findings when
      multiple tests were performed. All findings that are significant are after
      Bonferroni. The study was Institutional Review Board (IRB) approved. A total of
      325 consenting patients were studied from October 1996 to April 1998. The
      patients consisted of 174 men and 151 women, with an average of 35.8 years of
      age. The race of the patients was 70% African American and 20% Hispanic. Of the
      total of 325 patients, 20.3% (74) required an anti-emetic because of nausea
      and/or vomiting. A significant difference occurred in causes of pain for women (t
      = 2.79, P <.007). The causes of pain for women were general pain, fracture,
      abdominal, back pain, and other as compared with men with gun shot wounds,
      general, fracture, low back, and flank. Women showed no significant difference
      with regard to presenting pain scale (t =.122, P <.903), first drug given (t =
      1.643, P <.101), and first dose given (t =.708, P <.408). The majority of
      patients received morphine (55.4%), followed by meperidine (24.3%), and
      hydrocodone (13.5%). The most frequent route of administration was intravenous
      (IV, 45.2%), intramuscular (IM, 35.7%), with oral being the least frequent route
      (19.1%). There was a difference for women with first route given (t = 2.543, P
      <.01) and requires anti-emetic (t = 3.06, P <.002). The majority of women
      received IM (58.6%) versus IV (37.7%), whereas the majority of men (62.3%)
      received IV versus IM (41.4%). A significant number of patients became nauseated
      and/or vomited from Emergency Department-administered narcotics. The nausea and
      vomiting was associated with female sex and the cause of pain. A comparative
      study of other pain medications versus narcotics for incidence of induced nausea
      and emesis would be useful.

PMID- 11992332
TI  - Surfing injuries.
AB  - The purpose of this study was to describe the relative frequency, pattern, and
      mechanism of surfing injuries. Descriptive data of surfing injuries was collected
      by using a Web site-based interactive multiple choice survey. Data was collected
      from May 1998 to August 1999. Completed surveys were obtained from 1,348
      individuals reporting 1,237 acute injuries and 477 chronic injuries. Lacerations
      accounted for 42% of all acute injuries, contusions 13%, sprains/strains 12%, and
      fractures 8%. Thirty-seven percent of acute injuries were to the lower extremity,
      and 37% to the head and neck. Fifty-five percent of injuries resulted from
      contact with ones own board, 12% from another surfer's board, and 17% from the
      sea floor. Sixty-seven percent of acute surfing injuries are caused by board
      contact. Older surfers, more expert surfers, and those surfing large waves have a
      higher relative risk for significant injury. Equipment modifications are
      suggested that may decrease the risk for injury.

PMID- 11992333
TI  - The impact of smoking-related illness in the ED: an attributable risk model.
AB  - The objective of this study was to estimate the clinical and economic impact of
      smoking among adult emergency department (ED) patients. An attributable risk
      analysis of patients seen in 2 urban EDs in 1998 was performed. Data were
      obtained from hospital databases, national sources describing the prevalence of
      smoking in the state, and risk ratios for smoking-related illnesses. Of 78,617
      patient visits, 12,573 (16.0%) had any smoking-related International
      Classification of Diseases, 9th Revision code. The smoking-attributable risk
      fraction (SARF) for all patients was 4.9% (95% confidence interval [CI] 4.7%
      5.0%). Of 13,245 admissions, 6.8% (95% CI 6.4%-7.2%) were smoking attributable.
      Of $296,962,685 in hospital charges, 10.0% (95% CI 9.9%-10.1%) were smoking
      attributable. The SARFs for ED visits, admissions, and charges for men were
      higher than for women (all P <.0001). Smoking-attributable illness accounts for
      4.9% of ED adult visits, 6.8% of ED adult admissions, and 10.0% of hospital
      charges. The use of ED-based smoking intervention remains to be determined.

PMID- 11992334
TI  - The high prevalence of pain in emergency medical care.
AB  - Although there is a widely held belief that pain is the number 1 complaint in
      emergency medical care, few studies have actually assessed the prevalence of pain
      in the emergency department (ED). We conducted an analysis of secondary data by
      using explicit data abstraction rules to determine the prevalence of pain in the
      ED and to classify the location, origin, and duration of the pain. This
      retrospective cross-sectional study was conducted at an urban teaching hospital
      in Indianapolis, IN. Charts from 1,665 consecutive ED visits during a 7-day
      period were reviewed. Pain was defined as the word pain or a pain equivalent word
      (including aching, burning, and discomfort) recorded on the chart. Of the 1,665
      visits, 61.2% had pain documented anywhere on the chart, 34.1% did not have pain,
      and 4.7% were procedures. Pain was a chief complaint for 52.2% of the visits.
      This high prevalence of pain has important implications for the allocation of
      resources as well as educational and research efforts in emergency medical care.

PMID- 11992335
TI  - Field triage of trauma patients: improving on the Prehospital Index.
AB  - The purpose of the present study was to evaluate the predictive ability of the
      Prehospital Index (PHI) in identifying injury severity and to develop a trauma
      triage scale that incorporates, along with the PHI, a subset of time independent
      variables to improve the predictive ability of the PHI-based triage instrument.
      This study included 1,291 trauma patients treated in Montreal, Canada. The
      developed trauma triage protocol was based on logistic regression analysis, in
      which the model that predicts the data best was selected by using Bayesian
      information criterion. The selected regression model included the variables age,
      body region injured, mechanism of injury, comorbidity, and PHI. This algorithm
      was a substantial improvement in detecting major versus non-major injuries (major
      injury defined based on death, intensive care unit admission, and surgery
      intervention) over the PHI alone (area under the receiver operating
      characteristic curve: 0.76 v 0.66, P <.05). Considering time independent
      variables could lead to better injury triage decisions.

PMID- 11992336
TI  - Prevalence of traumatic brain injury in an ED population.
AB  - The objective of this study was to determine prevalence of traumatic brain injury
      (TBI) in an emergency department (ED) population. Questionnaires were
      administered to patients in an urban, university, trauma center ED. All
      respondents provided demographics; patients reporting TBI were asked age at
      injury, if they experienced loss of consciousness (LOC), mechanism, or if medical
      attention was sought. Five hundred one patients completed the survey. Forty-one
      percent reported TBI; 23% had TBI with LOC. Mean age at injury was 21.5 years.
      Mechanism was evenly distributed among sports, assaults, falls, and motor vehicle
      crashes (MVC). Medical attention was sought for 61% of injuries. Men were more
      likely to report TBI (P <.001). Medical attention was more likely if MVC or LOC
      and less likely in sports-injured patients (all P <.01). Twenty-five percent of
      patients with TBI sustained repeat injury by the same mechanism. Prevalence of
      TBI in this population is high. Many occur by mechanisms that potentially are
      preventable.

PMID- 11992337
TI  - Injury surveillance in the ED: design, implementation, and analysis.
AB  - Comprehensive, population-based surveillance for nonfatal injuries requires
      uniform methods for data collection from multiple hospitals. To show issues
      related to design and implementation of multihospital, emergency department (ED),
      injury surveillance, a city-wide system in the United States is discussed. From
      October 1, 1995 to September 30, 1996 all injury-related ED visits among District
      of Columbia residents <3 years of age were ascertained at the 10 hospitals where
      city children routinely sought care. Information was abstracted from 2,938 injury
      related, ED visits (132.7 visits/1,000 person-years). Based on this experience,
      suggestions to facilitate design of multihospital, injury surveillance in other
      locations are offered. Importantly, injury-related visits were reliably
      ascertained from ED logs, and for most variables, a systematic sample of injury
      related visits was representative of the total injured population. However, there
      is a need for more complete documentation of circumstances surrounding injuries
      and for standardization of data elements on ED logs and treatment records.

PMID- 11992338
TI  - Variation in patient management based on ECG interpretation by emergency medicine
      and internal medicine residents.
AB  - This study was performed to determine the impact of electrocardiogram (ECG)
      interpretation on urgent patient care decisions by internal medicine (IM) and
      emergency medicine (EM) resident physicians. Six clinical scenarios and ECGs were
      given to 31 IM residents and 31 EM residents at a university medical center.
      Based on the ECG interpretation, the residents were asked to select the best
      patient management from a list of choices. IM and EM residents were equally
      likely to choose the correct management for complete heart block (90% IM v 97%
      EM, P = NS), and pulseless ventricular tachycardia (VT) (94% IM v 97% EM, P =
      NS). IM residents were less likely to choose the correct management for acute
      posterior wall myocardial infarction (MI) (26% IM v 74% EM, P <.0001) and
      unstable supraventricular tachycardia (SVT) (87% IM v 100% EM, P <.05). Residents
      in both programs were equally likely to misinterpret left ventricular hypertrophy
      (LVH) (23% IM and 16% EM, P = NS) and benign early repolarization (BER) (48% IM
      and 52% EM, P = NS) as acute myocardial ischemia when presented with a clinical
      history not suggestive of cardiac ischemia. IM and EM residents were equally
      likely to choose the correct management for complete heart block and pulseless
      VT. Compared with EM residents, IM residents were less likely to choose the
      correct management of posterior wall MI and unstable SVT. Both IM and EM
      residents were prone to misinterpreting LVH and BER as acute myocardial ischemia.
      Resident education in both specialties should focus on ECG interpretation skills
      to improve patient management decisions.

PMID- 11992339
TI  - Early identification of patients with an acute coronary syndrome as assessed by
      dispatchers and the ambulance crew.
AB  - This study was performed to evaluate the possibility of early identification of
      patients with an acute coronary syndrome who are transported by ambulance. All
      patients in the community of Goteborg who were transported by ambulance over a
      period of 3 months owing to symptoms raising any suspicion of an acute coronary
      syndrome were studied. In all 930 cases that were included in the survey, 130
      (14%) had a final diagnosis of acute myocardial infarction (AMI) and 276 (30%)
      had a final diagnosis of an acute coronary syndrome. Independent risk indicators
      for development of AMI were: male sex (odds ratio 1.70; 95% confidence limits
      1.02-2.84), cold and clammy on admission of the ambulance crew (odds ratio 2.07;
      95% confidence limits 1.23-3.49) and showing electrocardiogram (ECG) signs of
      myocardial ischemia on admission to the emergency department (odds ratio 8.78;
      95%confidence limits 5.28-14.61). Independent predictors for development of an
      acute coronary syndrome were: male sex (odds ratio 1.97; 95% confidence limits
      1.30-2.99), a history of angina pectoris (odds ratio 3.41; 95% confidence limits
      2.24-5.26), cold and clammy on admission of the ambulance crew (odds ratio 1.95;
      95% confidence limits 1.21-3.15), and ECG signs of myocardial ischemia on
      admission to the emergency department (odds ratio 5.55; 95% confidence limits
      3.63-8.58). Among patients seen by the ambulance crew with symptoms raising any
      suspicion of an acute coronary syndrome, predictors for that diagnosis included
      male sex, a history of angina pectoris, patients being cold and clammy on
      admission of the ambulance crew, and ECG signs of myocardial ischemia on
      admission to the emergency department.

PMID- 11992340
TI  - Diagnostic value of procalcitonin levels as an early indicator of sepsis.
AB  - Researchers and clinicians have been investigating and implementing various
      methods of early diagnosis for sepsis before documentation of infection. The aim
      of this study was to outline the efficiency of procalcitonin (PCT), C-reactive
      protein (CRP), and white blood cell count (WBC) in determining the early
      diagnosis of sepsis in the emergency department. Between January 1999 and
      September 2000, 34 patients with signs of systemic inflammatory response syndrome
      (SIRS) were enrolled in the study. The patients were divided into 2 groups
      according to non-suspected sepsis and suspected sepsis clinically. Admission PCT
      was significantly higher in suspected sepsis group (median 68.7 microg/L; lower
      [L] = 15.24 microg/L, upper [U] = 120.54 microg/L) compared with the unsuspected
      sepsis group (.23 microg/L; L =.10 microg/L, U =.44 microg/L). PCT values were
      compared with WBC and CRP levels. Predictive accuracy for sepsis expressed as
      area under the receiver operating characteristic (ROC) curve was.88 for PCT,.44
      for WBC, and.34 for CRP. PCT can probably be used as a predictive marker in
      bacterial infections in emergency departments.

PMID- 11992341
TI  - Societal opinions regarding CPR.
AB  - Resuscitative measures are traditionally undertaken for most patients with
      cardiac arrest, unless an advance directive exists. This long-standing default
      presumption of patients' wishes to undergo resuscitation has never been proven.
      This study was undertaken to determine societal preferences of the general public
      regarding resuscitation. A cross-sectional survey was administered at community
      events to 724 volunteer participants over a 16-month period. For 6 hypothetical
      clinical scenarios (previously piloted and validated), respondents indicated
      personal preferences regarding resuscitation attempts for themselves. Most
      respondents indicated preferences for resuscitative efforts in a scenario
      depicting a young, healthy patient (96%), whereas few would desire resuscitative
      efforts for an elderly, debilitated patient (27%) (P <.01, Fisher's exact test).
      Nearly all (98%) respondents showed a trend (by scalogram analysis) toward
      refusal of resuscitative efforts in scenarios depicting more elderly, debilitated
      patients. Respondents had inaccurate perceptions of survival rates after cardiac
      arrest; the mean estimated survival rate was 50% (range 0%-100%). Although the
      majority of respondents had a personal physician (82%), only 10% of respondents
      had ever discussed death or resuscitation with their physicians. This study shows
      a trend in personal opinion among the general public toward refusal of
      resuscitative efforts in clinical scenarios with poor prognoses. Because so few
      patients have completed advance directives, physician awareness of such public
      opinions may be useful in decision-making in end-of-life care, particularly when
      caring for patients without advance directives. These public opinions support the
      feasibility of establishing societal consensus regarding resuscitation
      preferences, which may be useful in the development of federal and local
      guidelines and policies.

PMID- 11992342
TI  - ED utilization of computed tomography in a poisoned population.
AB  - The objective of this prospective, analytic study was to identify predictors and
      describe the demographic and clinical correlates of head computed tomography (CT)
      evaluation in patients with poisoning or drug overdose and altered mental status.
      Forty-three patients that were evaluated by head CT and 109 that were not
      evaluated by head CT were entered into the study at a poison control center. None
      of the 43 scanned patients had any acute findings on head CT. A logistic
      regression model yielded 4 predictors that were statistically associated with the
      ordering of a head CT scan: Glasgow Coma Scale (GCS) < or = 8 (odds ratio [OR]:
      2.3; 95% confidence interval [CI] 1.03-5.7); age > or = 41 years (OR 5.3; 95% CI
      2.2-13); use of drugs or abuse by history (OR 2.8; 95% CI 1.04-7.6); and
      witnessed seizure activity (OR 4.8; 95% CI 1.3-17.9). We also tested 2 additional
      models to identify predictors of hospital admission, 1 with and 1 without CT scan
      included as a covariate. In the first model, only GCS </=8 was a significant
      predictor of admission (OR 10.7; 95% CI 2.4-47.2). When the use of head CT was
      added to the second model, it also emerged as an independent explanatory
      predictor of admission (OR 4.8; CI 95% 1.2-20.4) in addition to GCS (OR 10.1; 95%
      CI 2.2-45.4). In this pilot study, patients presenting to the emergency
      department (ED) with suspected poisoning or drug overdose were found to have a
      low likelihood of abnormal findings on head CT scan. Those among whom CT scans
      were obtained were more likely to be admitted to the hospital from the ED,
      despite negative findings.

PMID- 11992343
TI  - Significant hemoperitoneum in blunt trauma victims with normal vital signs and
      clinical examination.
AB  - Clinical examination of the abdomen is generally reliable in stable trauma
      patients with no distracting or head injury. Patients involved in relatively
      minor trauma with normal examinations can be safely sent home in most instances.
      We report 6 cases of blunt abdominal trauma that had completely normal clinical
      examinations and vital signs but were found to have significant hemoperitoneum on
      trauma ultrasound examination. Four of the patients were examined for educational
      purposes just before planned discharge from the emergency department. These cases
      suggest that a screening ultrasound examination may have a role in the evaluation
      of most blunt trauma patients.

PMID- 11992344
TI  - Research training among pediatric emergency medicine fellows.
AB  - This study examined research training characteristics among pediatric emergency
      medicine (PEM) fellows. A 45-question survey was mailed to all registrants of the
      1998 National PEM Fellows' Conference. Descriptions of curricular design and
      administrative support components, perceived barriers, and subjective stress
      related to research were obtained. Surveys were returned by 67 of 79 fellows
      (85%). A total of 92.5% reported didactic instruction relating to research with
      relatively higher amounts in research design and biostatistics, and lower amounts
      in electronic review of the literature, applying to the institutional review
      board, ethics, and applying for grants. The most commonly cited barriers to more
      active participation in research were inadequate experience, inadequate time, and
      lack of administrative help. Stress in relationship to research was high (5.1 on
      a 1-7 Likert scale). PEM fellows report increasing levels of didactic exposure
      and administrative support for conducting research, however, PEM fellows still
      report experiencing significant amounts of stress and a number of perceived
      barriers.

PMID- 11992345
TI  - Traumatic injuries caused by hazing practices.
AB  - Hazing is defined as committing acts against an individual or forcing an
      individual into committing an act that creates a risk for harm in order for the
      individual to be initiated into or affiliated with an organization. Hazing is an
      enduring activity with roots that date back to the ancient and medieval eras. It
      has become increasingly prevalent in fraternities and sororities, high school and
      college athletic organizations, the military, professional sports teams, and
      street gangs. Scant information is available in the medical literature regarding
      hazing. This article reviews the history of hazing, provides statistics regarding
      its prevalence, presents information on specific hazing practices and consequent
      traumatic injuries, and assesses alcohol's influence on hazing. It also offers
      recommendations on how to recognize victims of hazing in the Emergency Department
      and proposes guidelines for their treatment. Current legislation and information
      on the prevention of traumatic injuries from hazing are discussed.

PMID- 11992346
TI  - Orthopedic pitfalls in the ED: radiographically occult hip fracture.
AB  - Acute hip fracture is among the most commonly encountered orthopedic injuries
      seen by the emergency physician. The majority of these fractures can be readily
      diagnosed on the basis of clinical findings and plain radiographs. When initial
      films are negative or equivocal, but a high clinical suspicion exists for a hip
      fracture, additional diagnostic studies need to be performed because significant
      morbidity can result from ambulation on an unrecognized fracture. The emergency
      physician needs to remain vigilant for this potential orthopedic pitfall. This
      review article examines the clinical presentation, diagnostic techniques, and
      management options applicable to the emergency practitioner.

PMID- 11992347
TI  - Electrocardiographic ST segment elevation: left ventricular aneurysm.
AB  - Left ventricular aneurysm (LVA), also described as dyskinetic left ventricular
      segment, is defined as a localized area of infarcted myocardium that bulges
      outward during both systole and diastole. LVAs most often are noted after large
      anterior wall events but may also be encountered status after inferior and
      posterior wall injuries. In most cases, LVA is manifested
      electrocardiographically by varying degrees of ST segment elevation (STE), which
      may be difficult to distinguish from ST segment changes caused by acute
      myocardial infarction. The STE is generally associated with well-developed,
      completed Q waves in the anterior precordial leads, and there will not be
      reciprocal ST depression in the contralateral leads. This article focuses on the
      electrocardiographic findings useful in making the diagnosis of left ventricular
      aneurysm as well as distinguishing LVA from other STE syndromes.

PMID- 11992348
TI  - The prominent T wave: electrocardiographic differential diagnosis.
AB  - The prominent T wave is an abnormal T-wave morphology encountered in the earliest
      phase of ST-segment elevation acute myocardial infarction (AMI). Prominent T
      waves, however, are associated with other diagnoses, including hyperkalemia,
      early repolarization, and left ventricular hypertrophy (LVH). This article
      focuses on the electrocardiographic differential diagnosis of the prominent T
      wave with the presentation of 4 illustrative cases. We also recommend that the
      designation hyperacute should refer exclusively to the prominent T waves of ST
      segment elevation AMI.

PMID- 11992349
TI  - Electrocardiographic T-wave inversion: differential diagnosis in the chest pain
      patient.
AB  - Inverted T waves produced by myocardial ischemia are classically narrow and
      symmetric. T-wave inversion (TWI) associated with an acute coronary syndrome
      (ACS) is morphologically characterized by an isoelectric ST segment that is
      usually bowed upward (ie, concave) and followed by a sharp symmetric downstroke.
      The terms coronary T wave and coved T wave have been used to describe these
      ischemic TWIs. Prominent, deeply inverted, and widely splayed T waves are more
      characteristic of non-ACS conditions such as juvenile T-wave patterns, left
      ventricular hypertrophy, acute myocarditis, Wolff-Parkinson-White syndrome, acute
      pulmonary embolism, cerebrovascular accident, bundle branch block, and later
      stages of pericarditis.

PMID- 11992350
TI  - Ethylene glycol causing mesenteric ischemia?

PMID- 11992351
TI  - Multiple carpometacarpal joint dislocation.

PMID- 11992366
TI  - Brush cytology of the biliary tract: retrospective study of 278 cases with
      histopathologic correlation.
AB  - Bile aspiration during endoscopic retrograde cholangiopancreatography or
      percutaneous transhepatic cholangiography has been used as a diagnostic tool in
      the evaluations of pancreatic and biliary tree strictures for the last two
      decades. However, recently biliary tract brush cytology has become the method of
      choice in evaluating pancreatic/biliary tract abnormalities. The aim of this
      study was to evaluate the accuracy of pancreatobiliary lesions by an endobiliary
      cytotechnique. From 1993-1999, 278 pancreatobiliary brushings were performed at
      our institutions. Cytologic material was air-dried for Diff-Quik stain or fixed
      in ethanol for Papanicolaou staining. The cytologic diagnoses were classified in
      three categories: 1) benign, 2) atypical/suspicious, or 3) malignant. Subsequent
      surgical biopsy was available in 87 (31%) patients. There were 150 males and 128
      females with a mean age of 63 yr (range 22-97); 167 (60%) were benign cases.
      Follow-up surgical material was available in 39 cases, seven of which showed
      adenocarcinoma; 67 of all cases (24%) were atypical/suspicious cases. Follow-up
      surgical material was available in 31 cases, 17 (55%) of which showed
      adenocarcinoma; 32 cases (12%) were malignant cases. Follow-up surgical material
      was available in 15 cases. All 15 cases were in agreement with the cytologic
      diagnosis. Twelve (4%) cases were unsatisfactory for cytologic examination.
      Follow-up surgical material was available in two cases. One case showed mucinous
      cystadenoma of the pancreas. The other case showed benign duct epithelium. Our
      study shows a sensitivity of 68% and a specificity of 100%. Of the atypical
      cases, 55% were malignant on follow-up biopsy. Brush cytology of pancreatobiliary
      strictures is the most widely used technique in the diagnosis of carcinoma, with
      a high degree of specificity.

PMID- 11992367
TI  - Utility and outcomes of fine-needle aspiration biopsy in Hodgkin's disease.
AB  - We present our 10-year experience, including clinical utilization and outcomes,
      with fine-needle aspiration biopsy (FNAB) in Hodgkin's disease (HD). Eighty-six
      cases from 68 patients with HD that were evaluated by FNAB were identified over a
      10-year period. Medical records of these 68 patients were reviewed. Thirty-seven
      patients with primary HD underwent 41 aspirates. A diagnosis of HD was yielded in
      12 and suggested in 13 cases (sensitivity 86.2%, false-positive 0%). Nine were
      diagnosed as atypical lymphoid cells, four as hyperplasia/other, and three as
      unsatisfactory. With these diagnoses, six patients began treatment without tissue
      exam. Thirty-five patients with suspected recurrent HD underwent 45 FNABs.
      Recurrent HD was confirmed in 15 and suggested in 12 aspirates (sensitivity
      81.3%, false-suspicious 14.3%). With these diagnoses, 22 patients began treatment
      for recurrence without tissue exam. FNAB is useful both for establishing a
      primary diagnosis and confirming recurrence in HD and thus has a high utilization
      at our institution. In many instances, patients can begin therapy, negating the
      need for formal tissue exam.

PMID- 11992368
TI  - Radiologically guided percutaneous fine-needle aspiration biopsy of the liver:
      retrospective study of 119 cases evaluating diagnostic effectiveness and clinical
      complications.
AB  - We reviewed 119 percutaneous, radiologically guided fine-needle aspirations (FNA)
      from 114 patients with liver masses to evaluate diagnostic effectiveness and
      complications of this procedure. Satisfactory material was obtained in 118 cases
      (99%), of which 78 were diagnosed as positive (66%), three suspicious (2%), five
      atypical (4%), and 32 (27%) as negative for malignancy. Compared to surgical
      biopsy (48 cases) and clinical data, the sensitivity and specificity of FNA for
      malignancy was 95.1% and 100%, respectively, yielding a positive predictive value
      of 100% and a negative predictive value of 88.8%. Four cytology cases (3.4%) were
      false-negatives (FN); all were interpretive errors. Four FN surgical biopsies
      (8.3%) were sampling errors. Minor complications occurred in three cases (2.5%).
      We conclude that FNA is safe and effective for determining the malignant
      potential of liver masses and should be the procedure of choice. Our experience
      suggests that having a pathologist present in the radiology suite provides
      optimal patient care.

PMID- 11992369
TI  - Myofibroblastoma of the male breast: a diagnostic problem on fine-needle
      aspiration cytology.
AB  - Myofibroblastoma is an uncommon neoplasm of the male breast. Herein, we describe
      the cytologic features seen in the fine-needle aspirate of a 45-year-old man. The
      smears were cellular with intimate association of tumor cells with extracellular
      matrix material. The cells were spindle to polygonal and were without significant
      atypia. Numerous mast cells were observed. Nuclear grooving was present only
      occasionally, although this was conspicuous histologically. The presence of
      hyaline bands in between tumor cells, another interesting feature, was
      appreciated retrospectively. This neoplasm was initially misinterpreted as a
      malignant soft tissue tumor. Awareness of the cytologic features coupled with
      mammography should prevent a misdiagnosis of this tumor.

PMID- 11992370
TI  - Aspiration cytodiagnosis of amyloid from vitreous fluid.
AB  - Amyloidosis of the vitreous body is a rare disorder that causes progressive
      visual loss. In this report, a 36-yr-old female with familial amyloidosis is
      described in whom a progressive reduction of vision in both eyes over the last 4
      yr was ascribed to vitreous opacities due to amyloid. A left pars plana
      vitrectomy was performed and an aspirated sample of the vitreous on cytologic
      examination showed vitreous strands admixed with abundant dense, pink, globular
      material which was intensely positive on Congo red staining and exhibited
      yellowish-green birefringence indicative of amyloid. This was further confirmed
      ultrastructurally, which showed the classical appearance of amyloid fibrils. The
      case is of interest not only in view of the rarity of the condition but also in
      view of the fact that as far as we are aware the cytodiagnosis of amyloid from an
      aspirate sample from the vitreous has not been previously described in the
      literature.

PMID- 11992371
TI  - Fine-needle aspiration cytology of a primary ectopic meningioma.
AB  - Meningiomas are benign tumors derived from arachnoid cells. Most commonly an
      intracranial lesion, meningiomas may be found extracranially in various anatomic
      sites. A 23-yr-old white female presented with left-sided palpable mass located
      submucosally in the floor of the mouth. CT scan revealed no evidence of mass
      elsewhere in the head and neck region. Fine-needle aspiration cytology (FNAC)
      showed loose and cohesive cellular fragments with lobular growth pattern and
      uniform round or ovoid cells. The diagnosis of low-grade salivary gland neoplasm,
      not further classified, was made. The tumor was locally excised. The differential
      diagnoses of an extracranial meningioma and pleomorphic adenoma were discussed at
      the frozen section. Based on light microscopic, immunohistochemical, and electron
      microscopic (EM) findings, the final diagnosis of an ectopic meningioma was
      rendered. Ectopic meningiomas may pose a diagnostic challenge to clinicians and
      cytopathologists. It is easily forgotten in the list of differential diagnosis at
      an ectopic site. Primary ectopic meningioma in a region containing salivary
      gland(s) may mimic benign and low-grade malignant salivary gland tumors in FNAC.

PMID- 11992372
TI  - Intramuscular low-grade myxoid neoplasm with recurrent potential (cellular
      myxoma) of the lower extremity: case report with cytohistologic correlation and
      review of the literature.
AB  - "Low-grade myxoid neoplasm with recurrent potential" (cellular myxoma) is a term
      recently used to describe a subset of soft tissue lesions with histology
      intermediate between intramuscular myxoma and low-grade myxofibrosarcoma or
      myxoid malignant fibrous histiocytoma (MFH), while resembling a deeper
      counterpart of superficial angiomyxoma. Their distinctive biological behavior is
      characterized by the potential to recur locally, in contrast to intramuscular
      myxoma, while having no potential to advance in grade or metastasize when
      compared to low-grade myxofibrosarcoma. We present a cytohistological correlation
      for an intramuscular location of such a tumor in the lower extremity of a 49-yr
      old male.

PMID- 11992373
TI  - FNAB cytology of chordoma masquerading as adenocarcinoma: case report.
AB  - We report a lesion of the mobile spine in a 77-yr-old white male who presented
      with lower back pain, radiating bilaterally to the legs, with numbness on walking
      and standing. Magnetic resonance imaging showed a large mass within L3-L4
      vertebral bodies; however, chordoma was not suspected or suggested. Fine-needle
      aspiration biopsy (FNAB) of the mass revealed mostly blood with isolated flat
      clusters of polygonal rounded epithelial-like cells in a myxoid background.
      Immunohistochemistry could not be performed on the FNAB specimen due to
      inadequate material for cell-block. A limited immunocytochemistry panel was
      performed on one cytology smear. The tumor cells were immunoreactive for
      cytokeratin. During primary and expert evaluation, these features were
      interpreted as metastatic adenocarcinoma. Prostate and thyroid were suggested as
      possible primary sites. An extensive clinical and radiological search did not
      reveal a primary lesion. Four years later, the patient underwent surgical
      decompression and stabilization of his lumbar spine to avoid a catastrophic
      collapse of spine with neurological deficit. Histomorphological features and
      immunohistochemical studies at this time confirmed the lesion as chordoma. This
      case highlights the significance of considering chordoma in the differential
      diagnosis of FNAB cytology of spinal column lesions suggestive of adenocarcinoma,
      especially when the clusters of low-grade epithelioid cells with vacuolated
      cytoplasm in a myxoid background do not show epithelial structures such as
      papillae, glands, or acini.

PMID- 11992374
TI  - Aspiration cytology of elastofibroma dorsi: case report with ultrastructural and
      immunohistochemical findings.
AB  - Elastofibroma is a well-recognized tumor-like process which typically occurs in
      the soft tissue of the shoulder. Although fine-needle aspiration (FNA) represents
      a quick and simple method for definitive diagnosis, the possibility of a false
      negative diagnosis is high due to the hypocellularity of the smears. However, a
      high index of suspicion based on the clinical presentation of a firm mass in a
      typical location in an elderly person, usually female, aids in the diagnosis. We
      describe the FNA findings of elastofibroma dorsi in an 89-yr-old woman which,
      although hypocellular, contained diagnostic aggregates of petaloid globules
      within a collagenous matrix. The cytologic material showed a green-yellow
      autofluorescence of the altered elastic fibers with ultraviolet light.
      Transmission electron microscopy revealed an elongated beaded appearance with
      small electron densities and obliteration of the central elastin core. The
      presence of a hypocellular aspirate with autofluorescent elastic fibers should
      suggest the possibility of elastofibroma dorsi.

PMID- 11992375
TI  - Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is
      cytopathological diagnosis possible?
AB  - Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare
      tumor of the thyroid gland which occurs predominantly in children, adolescents,
      and young adults. It usually presents as a painless neck or thyroid mass and only
      exceptionally as a diffusely enlarged thyroid gland, without metastatic disease
      at diagnosis. We report on the case of 12-yr-old girl who had diffusely enlarged
      thyroid gland for about 1 yr and was initially treated for thyroiditis. Fine
      needle aspiration biopsy (FNAB) was performed 8 mo after the first admission.
      Cytological examination of smears showed unusual morphological features. FNAB
      smears were cellular, with dissociated cells, naked oval nuclei, aggregates, and
      groups. Three main cell types were observed: spindle, epithelioid, and
      epithelial. These cells were uniform, cytologically bland, with few mitotic
      figures. The distinction between these cells was not always unequivocal. In the
      background of the smears abundant red extracellular material in the form of fine,
      dust-like granules and irregular patches were present. It was also observed in
      some aggregates and groups of tumor cells. Spindle and epithelioid cells were
      immunocytochemically diffusely pan-cytokeratin-positive. In the differential
      diagnosis, medullary thyroid carcinoma and SETTLE were suggested. The final
      histological diagnosis was SETTLE. In cases of SETTLE presented as a diffuse
      thyromegaly the correct diagnosis may be delayed because clinically and
      ultrasonographically thyroiditis is suspected. To avoid such a delay, FNAB should
      be used preoperatively. It can provide specific cytological diagnosis based on
      morphological features and certain immunocytochemical characteristics of the
      tumor.

PMID- 11992376
TI  - Aspiration biopsy in a case of apocrine adenocarcinoma with foam cells
      (myoblastomatoid or histiocytoid adenocarcinoma).
AB  - We found only one report of a case of apocrine adenocarcinoma with foamy cells
      diagnosed by aspiration biopsy. Herein, we describe a second case with cytologic,
      histologic, and immunohistochemical findings and discuss the differential
      diagnosis of foamy cells on aspiration smears obtained from mammary nodules.

PMID- 11992377
TI  - Histologic and fine-needle aspiration cytologic features of polycystic disease of
      the parotid glands: case report and review of the literature.
AB  - Polycystic disease of the parotid glands is a rare disorder, with only eight
      examples to our knowledge being reported in the literature. The disease presents
      as a painless enlargement of one or both parotid glands and does not appear to be
      associated with other disease processes within the head and neck, or with
      polycystic disease of the kidney, pancreas, or congenital fibrosis of the liver.
      The histology has been well described. The overall glandular architecture is
      preserved but the lobules are markedly distended by cysts whose lining appears to
      be intercalated duct in differentiation. Characteristic eosinophilic laminated
      spheroliths lie in many of the cystic spaces. Aspirate smears are characterized
      by a relatively clean background in which are distributed histiocytes, red blood
      cells, and small clusters of ductal epithelial cells. Polycystic disease of the
      parotid glands must be differentiated cytologically from mucous retention
      reaction, mucoceles, benign lymphoepithelial cysts, and cystic neoplasms,
      including Warthin's tumor, low-grade mucoepidermoid carcinoma, cystadenoma, and
      papillary cystadenocarcinoma.

PMID- 11992378
TI  - Utility of intraoperative consultation touch preparations.
AB  - Although intraoperative touch preparations (TPs) often are performed in
      conjunction with frozen sections, the comfort level of using TPs in actual
      practice and the effect of TP quality and cytologic experience on diagnostic
      accuracy have not been measured. To investigate the utility of intraoperative TPs
      and to compare them with that of frozen sections, five pathologists of differing
      levels of cytologic experience retrospectively reviewed 122 intraoperative TPs
      and frozen sections. Accuracy rates for individual pathologists were calculated
      and the accuracy using TPs was compared to that of frozen sections. TP accuracy
      was correlated with TP quality and cytologic experience. The mean rates of
      correct, incorrect, and atypical TP diagnoses were 88.5%, 4.1%, and 7.4%,
      respectively. The mean rates of correct, incorrect, and deferred frozen section
      diagnoses were 86.1%, 2.5%, and 11.9%, respectively. For the four pathologists
      with cytologic experience, both TP and frozen section diagnostic accuracy rates
      were similar; however, the pathologist who lacked cytologic experience had lower
      TP diagnostic accuracy. All pathologists who had cytologic experience requested a
      frozen section for cases with an atypical or incorrect TP diagnosis. In cases
      with a correct TP diagnosis a frozen section was requested 46.3% of the time. TPs
      of greater technical quality were associated with higher diagnostic accuracy. In
      conclusion, the use of performing TP and frozen section are complementary and
      result in increased diagnostic accuracy. For some pathologists, TPs may replace
      frozen sections in over 50% of cases.

PMID- 11992379
TI  - Diagnosis of melanoma aspirates on ThinPrep: the University of Michigan
      experience.
AB  - The purpose of this study was to compare the cytologic features of melanoma fine
      needle aspirates (FNAs) prepared by ThinPrep (TP) with those in conventional
      smears (CS) and to identify any diagnostic pitfalls. Fifty-one aspirates
      diagnosed as melanoma were obtained, 36 of which were prepared by both TP and CS.
      The preparations were evaluated for cellularity, cell aggregates, cellular
      appearance, melanin pigment, cytoplasmic, and nuclear features. Categorical data
      were analyzed by the chi-square test and continuous data by the Wilcoxin-signed
      rank test. Correlation was determined by Spearman's test for bivariate
      correlations (rho). Good correlation between the two methods was identified for
      the following features: cellularity, cell type, bi/multinucleated cells,
      cytoplasmic features, NC ratio, and presence of macronucleoli. TP exhibits
      coarser chromatin compared to CS (P = 0.005). Six of 36 CS contained large
      cellular groups; none of the TP contained them (P = 0.018). Twenty-five of 36 CS
      contained intranuclear inclusions as opposed to 12/36 TP (P < 0.001). The number
      of inclusions was significantly reduced on TP. The amount of intracellular
      melanin was the same with both techniques. Background melanin was markedly
      reduced on TP except when either trapped by fibrin or attached to cellular
      clusters (P = 0.006). Background blood was also markedly reduced on TP (P <
      0.005). In summary, the cytological features of TP and CS for FNA evaluation of
      melanoma correlate well; however, one needs to be aware of the cytologic
      alterations introduced by TP. TP is a sufficient preparation method in the
      diagnosis of melanoma FNA aspirates when performed by clinicians. It is also a
      useful adjunct in bloody or low-cellular aspirates, where it tends to reduce the
      background blood and concentrate the cells.

PMID- 11992380
TI  - Adenocarcinoma cells in peritoneal fluid mimicking histiocytes.

PMID- 11992381
TI  - O-phospho-L-tyrosine protects TP53 wild-type cells against ionizing radiation.
AB  - O-phospho-L-tyrosine (P-Tyr) has been reported previously to inhibit growth of
      several cancer cell lines at mM concentrations. In the present study, we
      investigated the effect of this compound on tumor cells and normal cells in
      combination with radiation exposure. It could be demonstrated for the first time
      that P-Tyr at microM concentrations protects TP53 wild-type cells against
      ionizing radiation (SF4 minus BBI = 0.28, SF4 plus BBI = 0.45). On the contrary,
      human transformed or tumor cell lines characterized by mutated or functional
      inactivated TP53 were not altered or increased in their radiation sensitivity
      (SF4 minus BBI = 0.32, SF4 plus BBI = 0.22). Treatment of wild-type TP53 cells
      with P-Tyr induced stabilization of TP53 within 3 and 16 hours and a subsequent
      increase in CDKN1A expression after treatment. Consequently, a 16-hours
      pretreatment of cells with P-Tyr led to a significant radioprotective effect.
      This was not observed in cell lines with mutated TP53, which shows no
      radioprotection by P-Tyr. Thus, the present data suggest that P-Tyr-mediated
      radioprotection is dependent on preirradiation stabilization of TP53. The results
      indicate that P-Tyr is a radioprotective agent that can potentially be very
      useful and easy to deliver for radiation protection in general and especially in
      radiation therapy of TP53-mutated tumors.

PMID- 11992382
TI  - In vitro effects of radiation on human retinoblastoma cells.
AB  - Retinoblastoma (Rb) is the most common intraocular tumor of childhood and has
      been demonstrated clinically to be very sensitive to external beam radiation
      (EBR). The purpose of this study was to determine the survival of Rb cell lines
      at different endpoints following irradiation. We also studied Rb-reconstituted
      cell lines postirradiation to gain insight into the role of Rb following DNA
      damage. Suspension cultures were exposed to single doses of 1, 2, 5, and 10 Gy.
      Following irradiation, cell viability and cell death was assessed for up to 72 hr
      using Trypan blue exclusion and acridine orange/ethidium bromide (AO/EB)
      staining, respectively. Morphological features were examined with light and
      electron microscopy (LM and EM). Clonogenic survival was assessed 2 weeks
      postirradiation. Cell cycle distribution was analyzed by flow cytometry. A time-
      and dose-dependent decrease in cell viability was induced in Y79 and WERI-Rb1
      cells following irradiation, although not below approximately 45% for the times
      and doses used. A similar but much-reduced effect on viability was observed in Rb
      reconstituted cells. AO/EB staining, LM, and EM revealed features characteristic
      of apoptosis following irradiation and a time- and dose-dependent increase in
      apoptosis was observed. For Y79 and WERI-Rb1 cells, 30-40% apoptosis was observed
      72 hr after 10 Gy irradiation; however, apoptosis was much reduced in Rb
      reconstituted cells (approximately 8% Y79LxRb28; approximately 18% WERILxRb8). Rb
      cell lines were extremely sensitive to radiation, although less so in Rb
      reconstituted lines, with clonogenic survivals after 2 Gy (SF2) of 0.14 for Y79,
      0.06 for WERI-Rb1, 0.36 for Y79LxRb28, and 0.19 for WERILxRb8. Postirradiation, a
      sub-G1 population was observed, consistent with radiation-induced apoptosis, and
      Rb-reconstituted cells displayed a prolonged G2 phase. The clonogenic survival
      parameters of Rb cell lines are consistent with clinical observations, where
      extreme sensitivity to irradiation has been reported. Additionally, Rb protein
      protected cells from DNA damage and may also play a role in radiation-induced G2
      delay. This in vitro approach provides a useful model for further radiobiological
      studies of Rb.

PMID- 11992383
TI  - Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione
      from ionizing radiation.
AB  - Lens epithelium disorganization, glutathione (GSH) depletion, and epithelial cell
      death have been incriminated in the cytopathogenic mechanisms that lead to
      cataract formation following UVB and x-ray exposures. The objective of this study
      was to determine the in vitro capacity of the aminothiol WR-1065, the active
      metabolite of amifostine, and anetholedithiolethione (ADT or Sulfarlem) to
      protect bovine lens epithelial cells against x-ray irradiation. WR-1065 and ADT
      were used at a concentration of 20 microM. A single dose of 10 Gy was delivered
      at a rate of 2 Gy/min. Fluorimetric assays were then performed using a neutral
      red probe to evaluate cell viability, a Hoechst 33342 probe (HO) to evaluate
      nuclear condensation and apoptosis, and a monobromobimane probe to estimate the
      intracellular GSH pool. Twenty-four hours after x-ray exposure, cells pretreated
      with WR-1065 showed increased GSH levels, improved cell viability, and decreased
      HO fluorescence in addition to a lesser proportion of cells with apoptotic
      nuclear modifications. Between 72 and 120 hr postirradiation, ADT-pretreated
      cells also showed increased intracellular GSH levels and cell viability and
      decreased HO fluorescence and apoptotic cell morphology. This in vitro study
      demonstrates that WR-1065 and ADT protects lens epithelial cells from x-ray
      injury; thus, ADT and amifostine are appropriate candidates for clinical trials
      in humans. They are currently used in preventing radiation-induced xerostomia and
      should be further tested in the prevention of late radiation-induced ocular
      complications such as sicca syndrome and cataract.

PMID- 11992384
TI  - Radiation effects on soluble metabolites in cultured HeLa cells examined by 1H
      MRS: changes in concentration of glutathione and of lipid catabolites induced by
      gamma rays and proton beams.
AB  - Cultured HeLa cells were irradiated with a single acute dose of either gamma rays
      (40 Gy) or low-energy proton beams (20 Gy). (1)H magnetic resonance spectra of
      intact cells harvested at different times after irradiation and of the
      correspondent perchloric acid (PCA) extracts prepared at different times after
      irradiation were run. Selected signals from glutathione and lactate were examined
      with the aim of investigating effects of irradiation on antioxidative stores and
      on mitochondrial activity. An increase of signal intensity of glutathione (GSH)
      takes place at 15 and 24 hr after irradiation, while a decrease of its signal
      intensity, accompanied by an increase of that of free glutamate, starts appearing
      48 hr after irradiation. Lactate signal increases 48 hr after irradiation.
      Signals from lipid catabolites were also examined to explore their sensitivity in
      predicting the response to radiotherapy. Intensity ratios of signals of
      glycerophosphorylcholine and choline to that of phosphorylcholine increase with
      time after irradiation. Irradiating cells with gamma rays or proton beams at half
      a dose produces effects comparable to the metabolic variations presented here.
      The present experiments allow more insight into the complex pattern of the
      changes of GSH by irradiation and indicate that magnetic resonance spectroscopy
      signals from GSH, glutamate, lactate, and lipid catabolites are affected by
      irradiation. Finally, these data represent a first indication that the relative
      biological efficiency for some metabolic damage of low-energy proton beams with
      respect to gamma rays can reach a value of 2.

PMID- 11992385
TI  - Radiosensitivity of human squamous carcinoma cell lines is associated with amount
      of spontaneous DNA strand breaks.
AB  - We asked whether the constitutive level of DNA strand breaks (SBs) in four human
      squamous carcinoma cell lines is associated with their radiosensitivity, measured
      by the clonogenic assay. Because impairment in DNA replication and the action of
      endogenous deoxyribonucleases are two major sources of DNA strand breaks under
      normal cell metabolism, we also analyzed DNA polymerase and DNA ligase activities
      as well as the functional status of Poly(ADP-ribose) polymerase (PARP) and
      nucleolytic degradation of genomic DNA. We showed that the two relatively
      radioresistant cell lines, UM-SCC-1 and UT-SCC-5, had a statistically significant
      lower constitutive level of DNA SBs, as measured by DNA precipitation technique,
      compared with the two relatively radiosensitive cell lines, UM-SCC-14A and UT-SCC
      9. We found that cell lines with a higher level of broken DNA tended to have a
      higher constitutive level of DNA polymerase alpha activity, measured by
      incorporation of [(3)H]dTTP in DNase I-activated DNA. UM-SCC-1, UT-SCC-5, and UM
      SCC-14A did not show any difference in DNA ligase activity when a nicked
      oligonucleotide was used as substrate. The most radiosensitive cell line, UT-SCC
      9, had a significantly lower ligation efficiency compared to the other three cell
      lines. The functional status of the PARP was the same in the four cell lines.
      Although none of the four cell lines showed a characteristic apoptotic or
      necrotic degradation of genomic DNA, when tested with the "plasmid rejoining
      assay," a significant degradation of the plasmid DNA in UT-SCC-9 was detected. We
      conclude that the high fraction of DNA SBs for UT-SCC-9, the most radiosensitive
      cell line, is most likely a consequence of low ligation efficiency combined with
      a relatively high DNA polymerase alpha activity and the nuclease degradation of
      DNA.

PMID- 11992386
TI  - Clinical significance of caspase-3 expression in pathologic-stage I, nonsmall
      cell lung cancer.
AB  - Caspase-3 is a cysteine protease that plays an important role in the process of
      apoptotic cell death. Whereas many studies on the clinical significance of
      apoptosis in the therapy of malignant tumors have been reported, little has been
      studied clinically on caspase-3. In the present study, the clinical significance
      of caspase-3 expression in resected nonsmall-cell lung cancer (NSCLC) and its
      correlation with incidence of apoptosis were examined. A total of 118 consecutive
      patients who had undergone complete resection for pathologic Stage I NSCLC were
      retrospectively reviewed. Caspase-3 expression was examined immunohistochemically
      using a polyclonal antibody that recognized uncleaved caspase-3. The 5-year
      survival rate for patients with strong expression of caspase-3 (66.6%) was
      significantly lower than that for patients with weak expression (82.1%, P =
      0.021). Expression of caspase-3 was not correlated with incidence of apoptosis,
      proliferative activity, or p53 status. Multivariate analysis confirmed that
      strong expression of caspase-3 was a significant factor to predict poor
      prognosis. These results suggest that enhanced expression of "uncleaved" caspase
      3, that is, inactivated caspase-3, was correlated with poor prognosis in resected
      NSCLC.

PMID- 11992387
TI  - Tissue/dose compensation to reduce toxicity from combined radiation and
      chemotherapy for advanced head and neck cancers.
AB  - This study was undertaken to quantify the reduction in normal tissue
      complications resulting from the aggressive management of advanced head and neck
      cancers (AHNCs) utilizing tissue/dose compensation (TDC). Thirty-nine patients
      with AHNC were treated on an intensive chemotherapy + radiation regimen. Eighteen
      of 39 patients were treated using TDC; the remaining 21 patients were radiated
      without TDC (NTDC). Acute and chronic toxicities, swallowing, speech function,
      and quality of life were assessed. The TDC group had a smaller radiation dose
      gradient across the entire treatment volume. Unscheduled treatment breaks were
      required in 11% of TDC patients as compared with 43% of the NTDC group (P =
      0.04). The TDC group had fewer Grade 3 or 4 acute and chronic toxicities and
      lower SOMA scores. At 3 months posttreatment, patients in the TDC group had
      better oral intake, lower pharyngeal residue, and better oropharyngeal swallowing
      efficiency and were able to swallow more bolus types. Patients in the TDC group
      also had better articulation. Use of TDC resulted in reduced treatment-related
      interruptions, decreased acute and chronic toxicities, and better speech and
      swallowing functions. Techniques to improve radiation dose conformality around
      the target tissues while decreasing the radiation dose to the normal tissues
      should be an integral part of aggressive combined modality therapy.

PMID- 11992388
TI  - Does the extent of surgery have an impact on the survival of patients who receive
      postoperative radiation therapy for supratentorial low-grade gliomas?
AB  - We evaluate the impact of extent of surgery (EOS) on survival of patients with
      supratentorial nonpilocytic low-grade gliomas (LGG) treated with postoperative
      radiation therapy (PORT). Sixty-five patients with pathologically confirmed
      supratentorial nonpilocytic LGG (36 astrocytomas and 29 oligodendrogliomas) were
      treated with PORT after different extents of surgery: 12 gross total resections
      (GTR), 27 minimal or subtotal resections (MR/SR), and 26 biopsies (B). EOS was
      confirmed with postoperative imaging. The median radiation dose delivered was
      5,940 cGy (range, 4,950-6,620 cGy). One of 12 patients (8%) in the GTR group and
      12 of 53 patients (23%) in the less than GTR group demonstrated contrast
      enhancement. The median follow-up was 61 months (range 5-194 month). The 10-year
      overall survival (OS) was 82.5% and 32% for the GTR and the less than GTR groups,
      respectively (P = 0.0008). The corresponding 10-year disease-specific survival
      (DSS) was 90% and 41.4%%, respectively (P = 0.001). Multivariate analysis showed
      that only contrast enhancement and EOS were predictors for OS and DSS. Our data
      suggest that EOS correlates with OS and DSS in patients who have PORT. GTR should
      be the goal if technically achievable without causing significant morbidity, and
      its combination with PORT is compatible with long-term survival.

PMID- 11992389
TI  - Preexisting histologic evidence of prostatitis is unrelated to postimplant
      urinary morbidity.
AB  - The presence and extent of prostatitis on the patients' preimplant biopsy slides
      was correlated with their postimplant course to determine if any relationship
      exists between histological prostatitis and postimplant morbidity. Biopsy slides
      from 56 patients treated with I-125 (144 Gy, TG-43), Pd-103 (125 Gy, NIST-1999),
      or Pd-103 plus supplemental external beam radiation (20-44 Gy) were studied. As
      part of ongoing prospective protocols, treatment-related morbidity is monitored
      by mailed questionnaires at 1, 3, 6, 12, and 24 months postimplant, using
      standard American Urologic Association (I-PSS) and Radiation Therapy Oncology
      Group criteria. Patient's preimplant biopsies, stained with standard hematoxylin
      and eosin, were retrieved for review by one uropathologist (LT). Separate
      evaluations of the degree and extent of inflammation in biopsy cores free of
      cancer and in cancerous biopsy cores were undertaken. Infiltrates were classified
      as periglandular if they were within 50 microns of a glandular structure. They
      were otherwise classified as stromal. Distribution of the inflammation was
      reported as focal, multifocal, or diffuse. The intensity of inflammation was
      separately graded as mild if there were fewer than 10 inflammatory cells per high
      power field, moderate if there were 10-200 cells per high-power microscopic
      field, or severe if there were more than 200 cells per field. In all cases the
      great majority of inflammatory cells were mononuclear, predominantly lymphocytes.
      Periglandular inflammation was most common, with 18% of patients having focal
      periglandular and 20% having multifocal periglandular inflammation on their
      preimplant biopsies. Cancer-related infiltrates were the second most common, with
      23% of patients having focal, 13% multifocal, and 13% diffuse cancer-related
      inflammation on their preimplant biopsies. Eight of the 55 patients developed
      postimplant urinary retention, requiring catheterization for 2 to 8 days. The
      overall incidence of postimplant urinary retention was low and there was no
      obvious relationship between the presence of inflammation on preimplant biopsy
      and the likelihood of postimplant urinary retention. AUA score changes at 1 and 6
      months postimplant were highly variable and unrelated to the presence or severity
      of periglandular or cancer-related inflammation. Considering the apparent lack of
      relationship between histological findings and clinical outcomes in the patients
      reported here, the authors conclude that histologic evidence of prostatitis is
      not a contraindication to brachytherapy.

PMID- 11992390
TI  - Dosimetric analysis of urinary morbidity following prostate brachytherapy (125I
      vs. 103Pd) combined with external beam radiation therapy.
AB  - The purpose of this analysis was to correlate isotope selection with the urinary
      symptoms of patients who received a combination of external beam radiotherapy
      (EBRT) and a transperineal interstitial permanent prostate brachytherapy (TIPPB)
      boost with either a (103)palladium ((103)Pd) or a (125)iodine ((125)I)
      radioisotope. Postimplant dosimetry was performed to evaluate both urethral dose
      and implant quality. The American Urologic Association (AUA) scores in both the
      (125)I and (103)Pd groups were similar initially. However, at 1, 3, 6, and 12
      months of follow-up, the mean AUA scores for the (125)I and (103)Pd patients were
      18 +/- 6 vs. 11 +/- 9, 17 +/- 7 vs. 11 +/- 7, 10 +/- 3 vs. 9 +/- 4, and 14 +/- 8
      vs. 7 +/- 5, respectively (P < 0.01). The only significant difference between the
      postimplant dose-volume histogram (DVH) of the (125)I and (103)Pd implants was
      the minimum dose that 90% of the urethra received (D(90)). The increased AUA
      score of the (125)I group was weakly correlated (R(2) = 0.20) with the D(90) dose
      but that of the (103)Pd patients was not (R(2) = 0.00). This suggests that the
      higher AUA score of the (125)I patients was not necessarily the result of the
      higher D(90) dose. Thus, patients who received (103)Pd experienced less urinary
      morbidity than those implanted with (125)I. We recommend further validating these
      findings in prospective studies in which the quality of the (125)I and (103)Pd
      implants can be evaluated.

PMID- 11992391
TI  - Local excision and postoperative radiation therapy for rectal adenocarcinoma.
AB  - Sixty-seven patients with early-stage adenocarcinoma of the rectum who had
      lesions thought to be unsuitable for either local excision alone or endocavitary
      irradiation were treated with local excision followed by postoperative radiation
      therapy. The purpose of this study was to evaluate the effectiveness of local
      excision followed by radiation therapy for treatment of rectal adenocarcinoma.
      The patients were treated between 1974 and 1999; follow-up time was 6 to 273
      months (median, 65 months). All living patients had follow-up for at least 2
      years. The indications for postoperative irradiation included equivocal or
      positive margins, invasion of the muscularis propria, endothelial-lined space
      invasion, poorly differentiated histology, and perineural invasion. Cox
      proportional hazards regression analysis was performed using six explanatory
      variables including tumor size, configuration (exophytic vs. ulcerative),
      histologic differentiation, pathologic T stage, endothelial-lined space invasion,
      and margin status. The time interval between treatment and development of
      recurrent disease was in the range of 11 to 48 months. The 5-year results were as
      follows: local-regional control, 86%; ultimate local-regional control, 93%;
      distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific
      survival, 90%. When the Cox proportional hazards regression analysis was
      performed for these endpoints, margin status influenced absolute survival (P =
      0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional
      control (P = 0.0439). Tumor configuration marginally influenced cause-specific
      survival (P = 0.0577). None of the variables had an influence on the endpoints'
      local-regional control, ultimate local-regional control with sphincter
      preservation, or distant metastasis. Five patients (7%) had severe complications;
      no complication was fatal. Local excision and postoperative radiation therapy
      results in a high probability of local-regional control and survival for selected
      patients with relatively early-stage rectal adenocarcinoma. Patients with
      ulcerative tumors may have a lower likelihood of cause-specific survival.

PMID- 11992392
TI  - Margin width as a determinant of local control with and without radiation therapy
      for ductal carcinoma in situ (DCIS) of the breast.
AB  - In order to assess the utility of margin width in relation to other
      histopathologic features as a determinant of local control in ductal carcinoma in
      situ (DCIS) of the breast, we retrospectively examined the treatment of 109
      breasts treated with (n = 54) or without adjuvant radiotherapy (n = 55). Median
      follow-up was 49 and 54 months for patients treated with excision alone (E) or
      excision plus adjuvant radiotherapy (E+XRT), respectively. Cases treated with
      E+XRT were significantly larger and had a trend towards closer surgical margins
      than those treated with E alone. For all cases, margin width < or = 1 mm and
      lesion diameter >15 mm were significantly associated with increased local
      recurrence. Lesion size < or = 15 mm was associated with no cases of local
      failure regardless of treatment arm. For lesions >15 mm in diameter, there was a
      significant decrease in 5-year local failure with E+XRT compared to E alone (21%
      vs. 36%, P = 0.03). Tumor margin >1 mm was associated with a low rate of 5-year
      local failure for either E alone or E+XRT (10.9% vs. 4.6%, P = NS). Tumor margin
      < = 1 mm had a high rate of local failure that was not significantly decreased by
      the addition of adjuvant radiotherapy. These results show that large diameter
      (>15 mm) and close surgical margins (< or = 1 mm) are the dominant risk factors
      for local recurrence in DCIS. E+XRT significantly decreased local failure risk
      compared to E alone for large lesions but not for those with close margins.

PMID- 11992393
TI  - Morbidity of adjuvant high-dose-rate brachytherapy for low to intermediate risk
      endometrial adenocarcinoma completely resected.
AB  - The aim of this retrospective analysis was to evaluate bowel and urinary acute
      and late morbidity in patients with low to intermediate risk endometrial
      carcinoma, submitted to total abdominal hysterectomy and bilateral salpingo
      oophorectomy, without lymphadenectomy, and postoperative high-dose-rate
      brachytherapy (HDR-B) as the sole treatment. From March 1996 to June 1998, 70
      patients were treated on an outpatient basis, to a total dose of 30-50 Gy, given
      in two fractions per week. A total of 4-5 fractions of 6-10 GY was delivered.
      Three patients (4.2%) developed severe bowel complications, with one patient
      experiencing severe rectal bleeding. Local control was observed in 68 (97.1%)
      patients. Five-year actuarial disease and complication-free survival were 94.3%
      and 96.8%, respectively. In conclusion, it seems that a modest dose fraction
      schedule of HDR-B yields very high local control rates and low morbidity rates.

PMID- 11992394
TI  - Patterns of failure in squamous cell carcinoma of the vagina treated with
      definitive radiotherapy alone: what is the appropriate treatment volume?
AB  - The purpose of this study was to review treatment results, sites of failure, and
      complications in relation to the irradiation volume for carcinoma of the vagina
      treated with radiotherapy alone. A retrospective review of 65 patients with
      histologically confirmed squamous cell carcinoma of the vagina who received
      definitive radiotherapy was undertaken. The 5-year cause-specific survival rates
      were as follows: Stage I, 91%; Stage IIA (paravaginal extension), 90%; Stage IIB,
      55%; Stage III, 89%; and Stage IVA, 62%. The pelvic disease control rates at 5
      years were as follows: Stage I, 74%; Stage IIA, 90%; Stage IIB, 79%; Stage III,
      89%; and Stage IVA, 67%. Recurrence in the pelvis occurred in 22% of patients.
      Eighty-five percent of pelvis recurrences were in the primary treatment field.
      Although pelvic control rates were not increased by use of larger treatment
      fields (>2,700 cm(3)), moderate acute and late effects were increased with these
      fields. Carcinoma of the vagina appears to have a different failure pattern than
      carcinoma of the cervix. The primary failure sites are the vagina and the
      paracolpal tissues and the inguinal nodes. Because of this, the superior edge of
      the pelvic fields does not have to extend above the bottom of the sacroiliac
      joints except with advanced lesions.

PMID- 11992395
TI  - Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood:
      outcomes of late effects on pituitary function and growth in long-term survivors.
AB  - It is well known that prophylactic cranial irradiation is highly effective in
      preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia
      (ALL). Nevertheless, there have been very few reports on the late effects,
      especially pituitary function and growth, in long-term survivors who were treated
      with 18 Gy cranial irradiation in childhood. The subjects consisted of 35
      children with ALL who were treated with prophylactic 18 Gy cranial irradiation at
      Kanagawa Children's Medical Center between October 1981 and February 1995. All
      patients received cranial irradiation after first attaining complete remission
      with induction chemotherapy, according to the treatment protocols prescribed by
      the Tokyo Children's Leukemia Study Group (TCLSG) and Tokyo Children's Cancer
      Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from
      2.2-15.0 years (mean 6.8). We evaluated their pituitary functions by measuring
      their pituitary hormone values 0.7-11.3 years (mean 6.0) after cranial
      irradiation and their growth by analyzing their height standard deviation score
      (SDS) at diagnosis of ALL and their final height SDS at the mean follow-up period
      of 8.2 years after cranial irradiation. Height SDS is defined as the difference
      between the patient's height and the mean height of their age and sex, divided by
      the standard deviation of their age and sex. Eight of 35 patients had ALL
      relapse, involving the bone marrow in seven patients and the CNS in only one. Six
      of the eight patients with relapse died 1.5-6.6 years after cranial irradiation
      and the other two patients were salvaged by further intensive therapies. The
      remaining 27 relapse-free patients have survived for 1.4-15.8 years (mean 10.1)
      after cranial irradiation. Twenty-six of the 29 survivors are long-term survivors
      of more than 5 years. Although there was one patient with an abnormal result in
      each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and
      prolactin (PRL), and two patients with abnormal results in thyroid-stimulating
      hormone (TSH) values, none of the patients had clinical symptoms of pituitary
      hormone abnormality and none required hormone supplements. The final height SDS
      decreased significantly compared with the height SDS at diagnosis of ALL in the
      long-term survivors (P = 0.001) and the height SDS of the patients who had
      received cranial irradiation at a young age tended to decrease gradually (P =
      0.019). However, no patient showed severe growth failure. It is considered that
      prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can
      effectively prevent CNS relapse and is unlikely to produce clinically significant
      late effects, although it may cause slight pituitary hormone abnormality.

PMID- 11992396
TI  - Doses near the surface during total-body irradiation with 15 MV X-rays.
AB  - An extended source-surface distance (SSD) is often employed in total-body
      irradiation (TBI) to obtain fields sufficiently large to encompass the total
      body. It is clinically desirable to administer a uniform dose to all tissues,
      including the surface, especially to counteract the skin-sparing of high-energy X
      rays. The electrons generated from the air contribute more to the dose near the
      surface at extended distances than at regular SSDs. However, if further increase
      of the dose at shallow depths is desired a spoiler can be employed. Monte Carlo
      simulations were used to study these effects for the electron component of the
      beam and the parameters needed for the pencil-beam dose calculation of this
      component. Measurements were performed to confirm these studies. The energy
      spectrum of electrons generated in air is independent of SSD. All the electrons
      in the beam, however, originate from the spoiler when one is used. The spectrum
      of these electrons is nearly independent of the SSD. The pencil-beam dose kernels
      were calculated using the derived electron spectra. To calculate doses in the
      buildup region with and without a spoiler, we use one pencil-beam kernel for the
      electrons generated in air and one for the electrons generated from the spoiler.
      Measured depth-dose data agreed with the calculation results.

PMID- 11992397
TI  - Modulation of radiotherapy photon beam intensity using magnetic field.
AB  - The purpose of this study was to explore the potential advantages of using strong
      magnetic fields to increase tumor dose and to decrease normal tissue dose in
      radiation therapy. Strong magnetic fields are capable of altering the
      trajectories of charged particles. A magnetic field applied perpendicularly to
      the X-ray beam forces the secondary electrons and positrons to spiral and
      produces a dose peak. The same magnetic field also prevents the electrons and
      positrons from traveling downstream and produces a lower dose region distal to
      the dose peak. The locations of these high- and low-dose regions are potentially
      adjustable to enhance the dose to the target volume and decrease the dose to
      normal tissues. We studied this effect using the Monte Carlo simulation
      technique. The EGS4 code was used to simulate the effect produced by a coil
      magnet currently under construction. The coil magnet is designed to support up to
      350 A operating current and 15 T peak field on windings. Dose calculations in a
      water phantom show that the transverse magnetic field produces significant dose
      effects along the beam direction of radiation therapy X-rays. Depending on the
      beam orientation, the radiation dose at different depths along the beam can be
      increased or reduced. This dose effect varies with photon energy, field size,
      magnetic field strength, and relative magnet/beam geometry. The off-axis beam
      profiles also show considerable skewness under the influence of the magnetic
      field. The magnetic field-induced dose shift may result in high dose regions
      outside the geometrical boundary of the initial radiation beam. We have
      demonstrated that current or near-term magnet technology is capable of producing
      significant dose enhancement and reduction in radiation therapy photon beams.
      This technology should be further developed to improve our ability to deliver
      higher doses to the tumor and lower doses to normal tissues in radiation therapy.

PMID- 11992398
TI  - Blocking a novel 55 kDa melanoma-associated cell surface antigen inhibits the
      development of spontaneous metastases and interactions with frozen lung section.
AB  - We recently identified a novel 55-kDa cell-cell adhesion protein (p55) whose
      expression is upregulated in primary melanomas in the transition from radial
      growth phase to vertical growth phase. However, the functional role of p55 in
      various steps of the metastatic process had not been investigated. We provide
      evidence that subcutaneous injection of metastatic melanoma variant T1P26 in
      immunosuppressed newborn rats rapidly caused spontaneous metastatic lung lesions
      that could be readily detected by histochemical analysis with the anti-p55
      monoclonal antibody (MAb) LY1. Subsequently, we were able to demonstrate that
      multiple subcutaneous injections of the LY1 MAb starting on the same day after
      tumor cell inoculation of T1P26 cells specifically blocked the formation of
      spontaneous lung metastases, yet had no effects on primary tumor growth,
      suggesting a critical role of p55 in the earlier steps of the intravasation
      process. To study later stages in spontaneous metastasis, we investigated the
      role of p55 in organ-specific cell adhesion of tumor cells in vitro. We showed
      that the T1P26 variant attached preferentially to lung frozen sections compared
      with other organs, reflecting the pattern of organ involvement of metastasis in
      vivo and that LY1 significantly blocked this interaction. However, no significant
      differences in attachment to lung sections were observed between the parental
      melanoma cell line M(4)Beu and its derived variant, although cellular topography
      analysis indicated a preferential attachment of a T1P26 variant on specific
      compartments of the lungs such as the perialveolar components, the endothelium
      and the vessel lumen of pulmonary venules. Attachment of the T1P26 variant to
      lung sections is not due to alterations of tumor cell adherence to basement
      membrane matrix by the LY1 MAb, suggesting that p55 is involved in cellular
      adhesion with cellular elements of the lung. p55 could represent a new functional
      constituent that contributes to the metastatic spread of melanoma cells by
      promoting the intravasation process and subsequent specific interactions between
      tumor cells and the target lung organ.

PMID- 11992399
TI  - The MEK/ERK pathway mediates COX-2-selective NSAID-induced apoptosis and induced
      COX-2 protein expression in colorectal carcinoma cells.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) can prevent colorectal tumorigenesis
      in humans and in rodents. In vitro and in vivo studies indicate that one of their
      principal antineoplastic avenues is the induction of apoptosis. We have shown
      previously that NS-398, which selectively inhibits cyclooxygenase-2 (COX-2) over
      cyclooxygenase-1, induces apoptosis of colorectal tumour cells and elevates COX-2
      protein expression. Here, we have determined that the extracellular signal
      regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway
      mediates these effects of NS-398. Treatment of HT29 colorectal carcinoma cells
      with 75 microM NS-398 caused activation of ERK-1/-2 but not of the p38 and c-Jun
      N-terminal kinase (JNK) mitogen-activated protein kinases. This was apparent at
      24 hr and maintained at 72 hr. U0126, a specific inhibitor of the ERK-activating
      kinases MEK-1/-2, prevented the activation of ERK induced by NS-398 and blocked
      the increase in COX-2 protein expression seen when HT29 cells were treated with
      NS-398 alone. The activation of ERK by NS-398 preceded and accompanied a decrease
      in attached cell yield and an increase in apoptosis. U0126 dose-dependently
      protected HT29 cells from these antiproliferative effects of NS-398, indicating
      an antiproliferative role for sustained ERK-1/-2 activation in response to this
      NSAID. These results point to a key role for the MEK/ERK signalling pathway in
      mediating the effects of a COX-2-selective NSAID on colorectal carcinoma cells.

PMID- 11992400
TI  - Thymidine kinase in epithelial ovarian cancer: relationship with the other
      pyrimidine pathway enzymes.
AB  - TK is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis.
      What roles TK may play in epithelial ovarian cancer and the relationships between
      TK and the other pyrimidine pathway enzymes remain unclear. We examined TK1 gene
      expression by RT-PCR and related it to gene expression of TS, TP and DPD in 69
      samples from epithelial ovarian cancer, 8 low-malignant-potential tumors, 16
      benign ovarian tumors and 34 normal ovaries. Additionally, cytosolic and serum TK
      activities were determined by radioenzymatic assay. TK1 gene expression, the
      ratio of TK1 to TS gene expression, that of TK1 to TP and that of TK1 to DPD were
      significantly higher in epithelial ovarian cancer than in normal ovaries. In
      epithelial ovarian cancer, TK1 gene expression correlated with cytosolic and
      serum TK activities, TS and TP gene expression and the ratio of TP to DPD gene
      expression. Patients with high-TK1 gene expression had a significantly poorer
      survival than those with low TK1 gene expression. Combined analysis demonstrated
      that the relative risk of cancer death for tumors with high TK1, high TS and high
      TP gene expression was greater than that for tumors with high TK1 gene expression
      alone. TK1 gene expression together with TS, TP and DPD gene expression may play
      important roles in influencing the malignant behavior of epithelial ovarian
      cancer. Combination therapy including TK inhibitor is a possible therapeutic
      intervention in patients with epithelial ovarian cancer.

PMID- 11992401
TI  - Mapping of two new epitopes on the apomucin encoded by MUC5AC gene: expression in
      normal GI tract and colon tumors.
AB  - Three hybridomas secreting monoclonal antibodies (MAbs) against human (62M MAb)
      or rat (463M and 589M MAbs) gastric mucins were isolated. These MAbs
      immunoreacted against a human recombinant protein encoded by the 3' region of the
      MUC5AC gene. We have mapped 2 new gastric mucin epitopes and the M1-f epitope
      previously characterized by the 19/21M1 MAbs on MUC5AC-encoded apomucin. The M1
      f, 463/589M and 62M epitopes are located in the MUC11p15/von Willebrand factor
      (vWF)-A3uD4 domain, in the D4-(vWF)-like domain and in the C- and CK-vWF-like
      domains of MUC5AC, respectively. The 463/589M and 62M MAbs stained the surface
      epithelium of human gastric mucosae, but not the normal colon mucosae (except
      463/589M MAbs, which immunoreacted with 5 of 49 cases). All hyperplastic polyps
      are stained strongly with the 463/589M MAbs and faintly with the 62M MAb. In
      addition, 463/589M epitope was detected in 64% of the adenomas and in 93% of the
      mucosae adjacent to adenocarcinomas; in contrast, only 9% of the adenomas and 29%
      of the mucosae adjacent to adenocarcinomas expressed the 62M epitope. The
      expression pattern of the 463/589M epitope in colonic carcinogenesis is different
      from that of the 19/21M1 epitope, although the 2 epitopes are encoded by MUC5AC
      gene.

PMID- 11992402
TI  - Tumor-infiltrating endothelial cells and endothelial precursor cells in
      inflammatory breast cancer.
AB  - Inflammatory breast cancer (IBC) is a specific type of breast tumor that
      generally has a poor prognosis, in spite of recent advances in treatment. In the
      present study, semiquantitative reverse transcriptase polymerase chain reaction
      examination of resected specimens showed that angiogenic factors, not
      lymphangiogenic factors, are overexpressed in IBC tumors, compared with non-IBC
      tumors. Immunohistochemical analysis of the specimens revealed a significantly
      higher population of tumor-infiltrating (TI) endothelial cells (ECs) or
      endothelial precursor cells (EPCs) in tumor-associated stroma of IBC specimens
      than in non-IBC specimens. In a previous study, we examined the phenotype of host
      cells in response to transplanted IBC cells, using an established human IBC
      xenograft model (WIBC-9) (Shirakawa et al., Cancer Res 2001;61:445-51). The data
      obtained in that study are consistent with the findings of the present study. To
      explore the therapeutic potential of blocking vascular endothelial growth factor
      (VEGF) and angiopoietin (Ang) pathways in IBC, established vectors encoding
      soluble Flt-1 (sFlt-1) and soluble Tie2 (sTie2) were injected directly into WIBC
      9. Both vectors produced growth inhibition ratios of WIBC-9 that were
      significantly higher than those of a non-IBC xenograft (MC-5). Also, both vectors
      suppressed WIBC-9 lung metastases. The efficacy correlated with the number of TI
      ECs/EPCs, which was determined by fluorescence-activated cell sorting. These
      ECs/EPCs incorporated acetylated lipoprotein and were integrated within a HUVEC
      monolayer in vitro culture on day 5.

PMID- 11992403
TI  - UV-B-type mutations and chromosomal imbalances indicate common pathways for the
      development of Merkel and skin squamous cell carcinomas.
AB  - Two developmentally highly divergent nonmelanoma skin cancers, the epidermal
      squamous cell carcinomas (SCC) and the neuroendocrine Merkel cell carcinomas
      (MCC), occur late in life at sun-exposed body sites. To determine whether these
      similarities may indicate common genetic alterations, we studied the genetic
      profile of 10 MCCs and analyzed 6 derived cell lines and 5 skin SCC lines by
      comparative genomic hybridization (CGH) and molecular genetic analyses. Although
      the MCCs were highly divergent-only 3 of the 10 tumors exhibited common gains and
      losses-they shared gain of 8q21-q22 and loss of 4p15-pter with the genetically
      much more homogeneous SCC lines. In addition, 2 of 5 SCC and 2 of 6 MCC lines
      exhibited UV-B-type-specific mutations in the p53 tumor-suppressor gene and a
      high frequency (9/11) of CC-->TT double base changes in codon 27 of the Harvey
      (Ha)-ras gene. Since 45% of the tumor lines were homozygous for this nucleotide
      substitution compared to 14% of the controls and in 1 MCC patient the wild-type
      allele was lost in the tumor, this novel polymorphism may contribute to tumor
      development. On the other hand, loss of 3p, characteristic for SCCs, was rare in
      MCCs. Although in 2 of 3 SCC lines 3p loss was correlated with reduced expression
      of the FHIT (fragile histidine triad) gene, the potential tumor suppressor mapped
      to 3p14.2 and 2 MCC lines with normal 3p showed aberrant or no FHIT transcripts.
      Taken together, in addition to the common UV-B-specific mutations in the p53 and
      Ha-ras gene, MCCs and SCCs also share chromosomal imbalances that may point to a
      common environmental-derived (e.g., UV-A) oxidative damage.

PMID- 11992404
TI  - The XAGE family of cancer/testis-associated genes: alignment and expression
      profile in normal tissues, melanoma lesions and Ewing's sarcoma.
AB  - The existence of XAGE genes was first reported after database homology searches
      for PAGE-like sequences identified 3 XAGE EST clusters. One of these clusters,
      XAGE-1, has in later studies been identified as a cancer/testis-associated gene.
      Here, we report the expression profiles of all 3 reported XAGE genes, as well as
      several splice variants of XAGE-1, in normal human tissues, Ewing's sarcoma and
      melanocytic tumors. We also provide the genetic structure of the corresponding
      genes. Moreover, by searching the databases for XAGE homologues, we identified 3
      additional GAGE-like genes. RT-PCR studies showed frequent expression in melanoma
      metastases and Ewing's sarcoma for 2 XAGE-1-derived transcripts. XAGE-2 was
      expressed at lower frequency in these tissues, while XAGE-3 was seen only in
      normal placenta. Due to a frameshift, the largest XAGE-1 putative protein is far
      less homologous to GAGE-like proteins than the other XAGEs. Interestingly, all
      GAGE-like genes contain a large secondary open reading frame, coding for putative
      proteins homologues to the XAGE-1 primary protein. The XAGE family of
      cancer/testis-associated genes is located on chromosome Xp11.21-Xp11.22. The data
      outline a superfamily of GAGE-like cancer/testis antigens, consisting of at least
      19 genes.

PMID- 11992405
TI  - Intragenic amplification and formation of extrachromosomal small circular DNA
      molecules from the PIP gene on chromosome 7 in primary breast carcinomas.
AB  - The PIP gene is expressed in exocrine glands and, in pathologic conditions, in
      breast cysts and breast cancers exhibiting apocrine features. It is localized on
      the long arm of chromosome 7, a region frequently alterated in mammary tumors. We
      previously described an abnormal restriction pattern of the PIP gene in 33% of
      prostate carcinomas analyzed. Here, we analyze the structure of the PIP gene in
      primary breast carcinomas. We report that part of the 3' end, including exon 3,
      intron C, two-thirds of exon 4 and a small portion of intron B, is amplified and
      involved in the formation of extrachromosomal spcDNA molecules in 3/14 (21.4%)
      breast cancers analyzed. The involvement of a well-defined intragenic region of a
      gene in the formation of spcDNA appears to be unprecedented. Since spcDNA has
      been suggested to serve as an enhancer of genetic instability, the PIP gene may
      be the target of genomic variability processes in breast cancer.

PMID- 11992406
TI  - Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I
      tax protein is associated with IL-2-independent growth of T cells.
AB  - Our aim was to examine the involvement of G(1) cell-cycle regulators in cell
      growth dysregulation induced by HTLV-I. Compared to uninfected cells, higher
      expression levels of cyclin D1 and D2 mRNA were detected in HTLV-I-infected T
      cell lines, which were at least in part mediated by the viral transforming
      protein Tax since Tax activated both cyclin D1 and D2 promoters in the human T
      cell line Jurkat. A Tax mutant that did not activate NF-kappaB failed to activate
      cyclin D1 and D2 promoters. Inhibitors of NF-kappaB (dominant negative IkappaBs
      mutants) suppressed Tax-dependent activation of cyclin D1 and D2 promoters,
      indicating that Tax-induced activation was mediated by NF-kappaB. Wild-type and
      mutant Tax capable of activating NF-kappaB, but not Tax mutant incapable of
      activating NF-kappaB, converted cell growth of a T-cell line from being IL-2
      dependent to being IL-2-independent; and this conversion was associated with IL-2
      independent induction of cyclins D1 and D2. Our data suggest that induction of
      cyclins D1 and D2 by Tax is involved in IL-2-independent cell-cycle progression
      as well as IL-2-independent transformation of primary human T cells by HTLV-I.
      High expression levels of cyclin D1 and D2 mRNAs were also detected in some
      patients with ATL. Our findings link HTLV-I infection to changes in cellular D
      type cyclin gene expression, transformation of T cells and subsequent development
      of T-cell leukemia.

PMID- 11992407
TI  - Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3
      activated killer T cells.
AB  - Adenosine, a purine nucleoside found at high levels in solid tumors, is able to
      suppress the recognition/adhesion and effector phases of killer lymphocyte
      mediated tumor cell destruction. Here, we demonstrate that adenosine, at
      concentrations that are typically present in the extracellular fluid of solid
      tumors, exerts a profound inhibitory effect on the induction of mouse cytotoxic T
      cells, without substantially affecting T-cell viability. T-cell proliferation in
      response to mitogenic anti-CD3 antibody was impaired in the presence of 10 microM
      adenosine (plus coformycin to inhibit endogenous adenosine deaminase). Antigen
      specific T-cell proliferation was similarly inhibited by adenosine. Anti-CD3
      activated killer T (AK-T) cells induced in the presence of adenosine exhibited
      reduced major histocompatibility complex-unrestricted cytotoxicity against P815
      mastocytoma cells in JAM and (51)Cr-release assays. Diminished tumoricidal
      activity correlated with reduced expression of mRNAs coding for granzyme B,
      perforin, Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL), as well as with diminished Nalpha-CBZ-L-lysine thiobenzylester
      (BLT) esterase activity. Interleukin-2 and interferon-gamma synthesis by AK-T
      cells was also inhibited by adenosine. AK-T cells express mRNA coding for A(2A),
      A(2B) and A(3) receptors, but little or no mRNA coding for A(1) receptors. The
      inhibitory effect of adenosine on AK-T cell proliferation was blocked by an A(3)
      receptor antagonist (MRS1191) but not by an A(2) receptor antagonist (3,7
      dimethyl-1-propargylxanthine [DMPX]). The A(3) receptor agonists (N(6)-2-(4
      aminophenyl)ethyladenosine [APNEA] and N(6)-benzyl-5'-N-ethylcarboxamidoadenosine
      [N(6)-benzyl-NECA]) also inhibited AK-T cell proliferation. Adenosine, therefore,
      acts through an A(3) receptor to prevent AK-T cell induction. Tumor-associated
      adenosine may act through the same mechanism to impair the development of tumor
      reactive T cells in cancer patients.

PMID- 11992408
TI  - Tumor targeting properties of monoclonal antibodies with different affinity for
      target antigen CD44V6 in nude mice bearing head-and-neck cancer xenografts.
AB  - The CD44 protein family consists of isoforms with tissue-specific expression,
      which are encoded by standard exons and up to 9 alternatively spliced variant
      exons (v2-v10) of the same gene. The murine MAbs U36 and BIWA-1, directed against
      overlapping epitopes within the v6 region of CD44, have previously been shown to
      efficiently target HNSCC. We herein report on the construction of 1 chimeric
      (BIWA-2) and 2 humanized (BIWA-4 and BIWA-8) derivatives of BIWA-1. Together with
      U36 and BIWA-1, these new antibodies were evaluated for affinity to the antigen
      in vitro as well as for biodistribution and efficacy in RIT using nude mice
      bearing the HNSCC xenograft line HNX-OE. As determined by surface plasmon
      resonance, the MAbs bound to CD44v6 with an up to 46-fold difference in affinity
      (K(d) ranging from 1.1 x 10(-8) to 2.4 x 10(-10) M) with the following ranking:
      mMAb U36 < hMAb BIWA-4 < hMAb BIWA-8 < mMAb BIWA-1 approximately cMAb BIWA-2. To
      evaluate their in vivo tumor-targeting properties, 2 MAbs with identical murine
      or human isotype were labeled with either (131)I or (125)I and administered
      simultaneously (50 microg/10 microCi each) as pairs showing a stepwise decrease
      in the difference in affinity: U36 vs. BIWA-1 (35.0-fold difference), BIWA-4 vs.
      BIWA-2 (14.0-fold) and BIWA-4 vs. BIWA-8 (4.0-fold). Biodistribution was assessed
      at 1, 2, 3 or 4 and 7 days after injection. Remarkably, for all 3 MAb pairs
      tested, the lower-affinity MAb showed a higher degree and specificity of tumor
      localization. The difference in tumor localization was more pronounced when the
      difference in affinity was larger. For example, 3 days after injection, the lower
      affinity mMAb U36 showed a 50% higher tumor uptake than the higher-affinity mMAb
      BIWA-1, while blood levels and uptake in organs were similar. After labeling with
      (186)Re (300 or 400 microCi), the same MAb pairs showed RIT efficacy consistent
      with the biodistribution data: (186)Re-U36 was more effective than (186)Re-BIWA
      1, (186)Re-BIWA-4 was slightly more effective than (186)Re-BIWA-2 and (186)Re
      BIWA-4 and (186)Re-BIWA-8 demonstrated similar efficacy. Based on these data, we
      conclude that antibodies with markedly lower affinity to a given target antigen
      (e.g., U36, BIWA-4) may show superior tumor targeting in comparison with higher
      affinity versions of these antibodies.

PMID- 11992409
TI  - Long-term freedom from recurrence in 2 stage IV melanoma patients following
      vaccination with tyrosinase peptides.
AB  - We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or
      HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently
      relapsing stage IV melanoma. Following resection of metastases and irradiation of
      brain metastases in 1 patient, both patients were without evidence of disease
      when receiving the first vaccination. While the patients had had 9 and 12,
      respectively, mostly s.c., relapses during the 3 years before vaccination, they
      experienced freedom from relapse for more than 2 years after vaccination. We
      found a T-cell response to the vaccine peptide in both patients in the peripheral
      blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population could be further
      characterized by 4-color flow cytometry in 1 patient, showing that the majority
      of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive
      and CCR-7-negative, characterizing them as effector T cells with the ability to
      mediate cytotoxicity and migrate to inflamed tissues. In this patient also,
      augmentation of the T-cell response to autologous tumor cells by vaccination
      could be detected. A single-site postvaccination relapse occurred in both
      patients, showing downregulation of tyrosinase expression in 1 patient, while
      normal expression levels for tyrosinase, MHC class I antigens and components of
      the antigen-processing machinery were found in the other patient. These results
      suggest that peptide vaccination resulted in a prolonged relapse-free interval in
      these high-risk patients.

PMID- 11992410
TI  - Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can
      induce HLA-A2-restricted and tumor-specific CTLs in the majority of
      gastrointestinal cancer patients.
AB  - To identify CTL-directed antigens in gastrointestinal cancer, we have
      investigated antigens recognized by the HLA-A2-restricted CTL line established
      from T cells infiltrating into colon cancer and report herein cleavage and
      polyadenylation specificity factor (CPSF) as a potent antigen holding peptides
      capable of inducing CTLs. Five peptides at amino acid positions 250-258, 392-400,
      534-542, 1296-1304 and 1359-1368 of CPSF, which were recognized by the CTL line,
      were found to have the ability to induce HLA-A2-restricted and tumor-specific
      CTLs in peripheral blood mononuclear cells of the majority (69%, 11/16) of
      gastrointestinal cancer patients with different HLA-A2 subtypes. Thus, these
      peptides might be appropriate molecules for use in the peptide-based specific
      immunotherapy of HLA-A2(+) patients with gastrointestinal cancers.

PMID- 11992411
TI  - High expression of tumor-associated antigen RCAS1 in pancreatic ductal
      adenocarcinoma is an unfavorable prognostic marker.
AB  - RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a recently
      identified human tumor-associated antigen expressed on various cancer cells. It
      is thought that tumor cells evade immune surveillance by expression of RCAS1,
      which induces apoptotic cell death in receptor-positive immune cells. The purpose
      of our study was to investigate the relation between RCAS1 expression and the
      clinicopathological variables and clinical outcome in patients with pancreatic
      adenocarcinoma. Immunohistochemical analysis for RCAS1 was performed on paraffin
      embedded specimens of 80 patients (mean age, 62 years) who underwent surgical
      resection for pancreatic adenocarcinoma. Of the 80 specimens, 77 (96%) were
      positive for RCAS1. No significant correlation was found between RCAS1 expression
      and age, gender, depth of invasion, tumor diameter, surgical margin, lymphatic
      invasion, venous invasion or histopathological grading. Borderline correlations
      between RCAS1 expression were noted for lymph node metastasis and stage (p =
      0.0608 and 0.0934, respectively). RCAS1 expression was very frequently observed
      and the survival of patients with high RCAS1 expression was significantly shorter
      than that of those with low expression (p = 0.0012). Multivariate analysis using
      the Cox regression model indicated that high RCAS1 expression was an independent
      prognostic factor (risk ratio, 3.090; p = 0.0090). These results suggested that
      RCAS1 might be a significant tumor marker for pancreatic adenocarcinoma and an
      unfavorable predictor for prognosis of patients who have undergone surgical
      resection.

PMID- 11992412
TI  - Novel epidemiologic evidence for the association between fermented fish sauce and
      esophageal cancer in South China.
AB  - Previous studies have suggested that fermented fish sauce is related to an
      increased risk for nasopharyngeal, thyroid and gastric cancers and has suspicious
      carcinogenic and promoting effects in the laboratory, but these reports have not
      investigated the association between this agent and esophageal cancer in
      population. Therefore, we investigated the relationship between esophageal cancer
      and consumption of fermented fish sauce, alcohol and tobacco after adjusting
      other risk factors using data from a large hospital-based case-control study in
      Chaoshan area of China. The subjects for analysis included 1,248 cases (median
      age 58.5 [range 29-82] years, 936 males, 312 females, some 50% with the habit of
      fermented fish sauce eating) with squamous cell carcinoma of the esophagus and
      the same amount of controls matched by sex and age. A significant increase in
      risk (OR 3.21; 95% CI 2.45-4.19) for eating fermented fish sauce compared to not
      eating and a significant dose-response relationship was found with the
      consumption of fermented fish sauce (p for trend < 0.001). In comparison based on
      the binary variables, the OR for the subjects with fermented fish sauce eating
      and current smoking was 15.5 with a 95% CI of 8.14-29.3, relative to those
      exposed to neither habit. The joint effect of fermented fish sauce (F) and
      smoking (S) was more than additive (F * S > F + S: 15.5 > 1 + (5.6 - 1) + (6.6 -
      1)), but the effect for fermented fish sauce and alcohol was not found. It is
      concluded that risks of esophageal cancer in the population were substantially
      associated with fermented fish sauce. Further epidemiologic and experimental
      study are required to find a biologic causal relationship between them.

PMID- 11992413
TI  - Does family history influence survival in breast cancer cases?
AB  - A few studies have suggested a relatively better prognosis for breast cancer (BC)
      cases reporting a positive family history (FH). We aimed at comparing the
      survival of patients according to FH in a large hospital-based series of 1,278 BC
      cases. Information on FH for BC was obtained at diagnosis by interview. All cases
      reporting a first- or second-degree FH for breast carcinoma were compared with
      cases without FH. Overall survival was estimated using a product-limit method.
      Hazard ratios (HRs) and the corresponding 95% confidence intervals (95% CIs),
      adjusted for confounding factors, were computed using proportional hazard models.
      Overall, 240 (18.8%) cases reporting, at diagnosis, a positive FH (156 with at
      least 1 first-degree relative and 84 with at least 1 second-degree relative) were
      compared with 1,038 patients without FH for BC. No significant differences were
      found in terms of distribution of age at diagnosis, tumor stage, nodal
      involvement, receptor status and histology. Cumulative survival rates at 5 years
      for cases without FH and with first-degree and second-degree FH for BC were 79.8
      (95% CI 77.0-83.0), 78.6 (95% CI 70.0-88.0) and 80.2 (95% CI 68.0-92.0),
      respectively (log-rank test, chi(2) (2) = 0.02, p = 1.0). After adjustment for
      age, pathologic size and nodal involvement, the HR among cases of invasive cancer
      with a first-degree FH of BC was 0.91 (95% CI 0.55-1.48); however, the HR for
      cases with second-degree FH was 1.18 (95% CI 0.62-2.25) compared to cases without
      FH. Our study, based on a large series of consecutive invasive BC cases, did not
      find any significant survival differences associated with a positive FH for
      breast carcinoma, suggesting the existence of a large heterogeneity among BC
      cases with FH.

PMID- 11992414
TI  - Recreational physical activity and ovarian cancer in a population-based case
      control study.
AB  - Results from epidemiologic studies of physical activity and ovarian cancer have
      been inconsistent, with 2 prospective studies reporting a modest positive
      association. We evaluated this relationship in a population-based case-control
      study conducted in Massachusetts and Wisconsin. Incident cases diagnosed between
      1991 and 1994 were identified through statewide tumor registries. Community
      controls were selected randomly from lists of licensed drivers and Medicare
      recipients. Participation in moderate and vigorous recreational physical activity
      at age 12, age 20 and 5 years prior to diagnosis was assessed by telephone
      interview. Data were available for 327 cases and 3,129 controls. Results were
      adjusted for age, parity and other ovarian cancer risk factors. Total and
      vigorous physical activity were not associated with a substantial decrease in
      ovarian cancer risk at any age. The relative risk (RR) for women reporting > or =
      7 vs. 0 hr/week of recent vigorous activity was 0.85 [95% confidence interval
      (CI) = 0.39-1.86; p for trend = 0.31]. When metabolic equivalent task (MET) hours
      of activity were estimated, only women in the highest category had any reduction
      in risk (RR for > 42 MET-hours/week at the reference age = 0.70; 95% CI = 0.36
      1.35; p for trend = 0.41). Overall, our results provide only limited support for
      an inverse association between recreational physical activity and risk of ovarian
      cancer.

PMID- 11992415
TI  - Leukaemia and non-Hodgkin's lymphoma in children of male Sellafield radiation
      workers.
AB  - Our objective was to investigate if there was (i) an excess risk of leukaemia/non
      Hodgkin's lymphoma among children of male radiation workers at the Sellafield
      nuclear installation in Cumbria, northwest England; (ii) a dose-response
      relationship between fathers' preconceptional irradiation and their children's
      risk of leukaemia/non-Hodgkin's lymphoma; and (iii) whether any observed
      association could be explained by demographic factors. We performed a cohort
      study of live births, 1950-1991 in Cumbria, followed up to age 25 years or the
      end of 1991, comparing the risk of leukaemia/non-Hodgkin's lymphoma among all
      9,859 children of male radiation workers to that among all 256,851 children of
      non-Sellafield fathers. Children of radiation workers had a higher risk of
      leukaemia/non-Hodgkin's lymphoma than other children [rate ratio (RR) = 1.9, 95%
      confidence interval (CI) 1.0-3.1, p = 0.05]. Adjustment for population mixing
      greatly reduced the excess risk in the village of Seascale, adjacent to
      Sellafield, but had little effect elsewhere. The risk increased significantly
      with father's total preconceptional external radiation dose (RR(100mSv) = 1.6,
      95% CI 1.0-2.2, p = 0.05). This dose-response was not reduced by adjustment for
      population mixing. Although our 13 exposed cases included 10 considered
      previously (Gardner et al., BMJ 1990;300:423-34), we used a cohort rather than a
      case-control design, with wider temporal and geographic boundaries, and confirmed
      the statistical association between father's preconceptional irradiation and
      child's risk of leukaemia/non-Hodgkin's lymphoma that they reported. The
      possibility remains that paternal preconceptional irradiation may be a risk
      factor for leukaemia/non-Hodgkin's lymphoma, and this effect may not be confined
      to Seascale.

PMID- 11992416
TI  - Case-control study of anthropometric measures and breast cancer risk.
AB  - A population-based case-control study of 1,233 incident breast cancer cases and
      1,241 controls was conducted in Alberta between 1995 and 1997 to examine the
      influence of anthropometric factors on the risk of breast cancer using several
      newly derived variables. Data on current height, weight and waist and hip
      circumference were collected by interviewers using standardized methods.
      Respondents recalled their body weight at each decade from age 20 to the referent
      year. Several variables were estimated, and unconditional logistic regression was
      used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No
      statistically significant associations for any of the estimated variables with
      breast cancer risk for premenopausal women (462 cases, 475 controls) were found.
      The results for postmenopausal women (771 cases, 762 controls) in the highest vs.
      lowest quartiles were, for waist circumference, OR = 1.30 (95% CI 0.97-1.73);
      waist-hip ratio, OR = 1.43 (95% CI 1.07-1.93); weight gain since age 20, OR =
      1.35 (05% CI 1.01-1.81); difference between maximum and minimum weights over
      adult lifetime, OR = 1.56 (95% CI 1.16-2.08); and the reference weight minus the
      minimum weight since age 20, OR = 1.47 (95% CI 1.10-1.97). Statistically
      significant trends in risk were observed for these variables. Effect modification
      with hormone replacement therapy use was found for most variables assessed for
      postmenopausal women, with much stronger associations found among never-users
      compared to ever-users. We found strong evidence that waist-hip ratio and weight
      gained over lifetime, as assessed by different variables, are postmenopausal
      breast cancer risk factors. These effects were independent of dietary intake and
      lifetime total physical activity.

PMID- 11992417
TI  - Adenovirus HSV-TK construct with thyroid-specific promoter: enhancement of
      activity and specificity with histone deacetylase inhibitors and agents
      modulating the camp pathway.
AB  - The successful use of tissue- or tumor-selective promoters in targeted gene
      therapy for cancer depends on high and selective activity. Tg is a thyroid
      specific protein that is expressed in the normal thyroid and a majority of
      thyroid tumors. In the present study, we show, using a luciferase reporter assay,
      that a construct containing the putative Tg promoter and enhancer is active in 4
      thyroid carcinoma cell lines (including 2 anaplastic thyroid carcinoma cell
      lines) and not in 5 cancer cell lines arising from nonthyroid tissues.
      Furthermore, both the activity and the specificity of this construct were
      increased by pretreatment with 8-Br-cAMP and the histone deacetylase inhibitor
      depsipeptide (FR901228). Expression of thymidine kinase in thyroid cancer cells
      infected with a recombinant adenovirus (Ad) carrying a Tg enhancer/promoter
      thymidine kinase expression cassette (AdTg enhancer/promoter-TK) correlated with
      the level of Tg enhancer/promoter activity in these cells. Under similar
      conditions, TK expression was not observed in cancer cell lines arising from
      nonthyroid tissues. Cells infected with AdTg enhancer/promoter-TK demonstrated
      preferential GCV sensitivity, with up to a 100,000-fold increase in GCV
      sensitivity in thyroid cancer cell lines compared to cancer cell lines of
      nonthyroid origin. The construct described herein can be used to selectively
      target thyroid cancer cells, and its expression can be modulated to further
      increase its specificity and selectivity, especially in anaplastic thyroid
      carcinoma cells, using 8-Br-cAMP and depsipeptide.

PMID- 11992418
TI  - Population-based survival analysis of colorectal cancer patients in Singapore,
      1968-1992.
AB  - Since the 1980s, colorectal cancer incidence in Singapore has ranked second to
      lung in males and females. We describe a population-based analysis of survival of
      colorectal cancer patients diagnosed from 1968 to 1992 in Singapore. Data of
      colorectal cancer patients diagnosed during 1968-1992 were retrieved from the
      Singapore Cancer Registry. Patients were passively followed up for death to the
      end of 1997. The final dataset consisted of 10,114 subjects. Observed and
      relative survival rates were calculated by stage (localized, regional metastases
      and distant metastases), age, ethnicity and calendar period for both genders.
      Over the study period, a significant progress in survival of colorectal cancer
      patients was observed. For localized cancer of the colon, the 5-year age
      standardized relative survival (ASRS) increased from 36% in 1968-1972 to 66% in
      1988-1992 for males and from 32 to 71% for females. For localized rectal cancer,
      the 5-year ASRS improved from 25 to 66% for males and from 23 to 66% in females.
      Similarly, improvement was observed in colorectal cancer patients with regional
      metastases, but not in those with distant metastases. Calendar year period and
      clinical stage of disease were identified as major significant prognostic factors
      of survival for colorectal cancer. The substantially improved colorectal cancer
      survival rates reflected the interplay of cancer control activities in various
      areas, such as health promotion, early diagnosis and treatment. Our study shows a
      unique changing pattern of survival experience for colorectal patients from a
      country undergoing rapid economic development.

PMID- 11992419
TI  - An artificial neural network considerably improves the diagnostic power of
      percent free prostate-specific antigen in prostate cancer diagnosis: results of a
      5-year investigation.
AB  - Our study was performed to evaluate the diagnostic usefulness of %fPSA alone and
      combined with an ANN at different PSA concentration ranges, including the low
      range 2-4 ng/ml, to improve the risk assessment of prostate cancer. A total of
      928 men with prostate cancer and BPH without any pretreatment of the prostate in
      the PSA range 2-20 ng/ml were enrolled in the study between 1996 and 2001. An ANN
      with input data of PSA, %fPSA, patient's age, prostate volume and DRE status was
      developed to calculate the individual's risk before performing a prostate biopsy
      within the different PSA ranges 2-4, 4.1-10 and 10.1-20 ng/ml. ROC analysis and
      cut-off calculations were used to estimate the diagnostic improvement of %fPSA
      and ANN in comparison to PSA. At the 90% sensitivity level, %fPSA and ANN
      performed better than PSA in all ranges, enhancing the specificity by 15-28% and
      32-44%, respectively. For the low PSA range 2-4 ng/mL, we recommend a first-time
      biopsy at an ANN specificity level of 90%. For PSA 4-10 ng/mL, we recommend a
      first-time biopsy based on the ANN at the 90% sensitivity level. Use of an ANN
      enhances the %fPSA performance to further reduce the number of unnecessary
      biopsies within the PSA range 2-10 ng/ml.

PMID- 11992420
TI  - Inhibition of experimental pulmonary metastasis by controlling biodistribution of
      catalase in mice.
AB  - In a previous study, we showed that targeted delivery of bovine liver catalase to
      hepatocytes by direct galactosylation augmented the inhibitory effect of the
      enzyme on experimental hepatic metastasis of colon carcinoma cells (unpublished
      data). Here, we examined the ability of catalase to inhibit tumor metastasis to
      the lung by controlling its biodistribution. Four types of catalase derivative,
      Gal-CAT, Man-CAT, Suc-CAT and PEG-CAT, were synthesized. Experimental pulmonary
      metastasis was induced in mice by i.v. injection of 1 x 10(5) colon 26 tumor
      cells. An i.v. injection of catalase (35,000 units/kg) partially, but
      significantly, decreased the number of colonies in the lung 2 weeks after tumor
      injection, from 93 +/- 29 (saline injection) to 63 +/- 23 (p < 0.01). Suc-CAT,
      Man-CAT and Gal-CAT showed effects similar to those of catalase on the number of
      colonies. However, PEG-CAT greatly inhibited pulmonary metastasis to 22 +/- 11 (p
      < 0.001). Furthermore, s.c. injection of catalase also greatly inhibited
      metastasis (11 +/- 6, p < 0.001). Neither inactivated catalase nor BSA showed any
      effects on the number of metastatic colonies, indicating that the enzymatic
      activity of catalase to detoxify H(2)O(2) is the critical factor inhibiting
      metastasis. (111)In-PEG-CAT showed a sustained concentration in plasma, whereas
      s.c.-injected (111)In-catalase was slowly absorbed from the injection site. These
      results suggest that retention of catalase activity in the circulation is a
      promising approach to inhibit pulmonary metastasis.

PMID- 11992421
TI  - Prospective cohort study of cigarette smoking and colorectal cancer risk in
      women.
AB  - Epidemiological studies have consistently found a positive association between
      cigarette smoking and risk of colorectal adenomas, so the absence of a clear
      association between smoking and colorectal cancer risk may seem paradoxical.
      However, if colorectal cancer develops only after an induction period of about 35
      years, as has been proposed recently, then studies in which all subjects have
      fewer than about 35 years between smoking commencement and assessment of outcome
      would be unlikely to detect this association. Few studies have examined smoking
      of several decades' duration among women. Therefore, in the cohort study reported
      here, we used proportional hazards models to estimate hazard ratios relating
      cigarette smoking to colorectal cancer risk among 89,835 women aged 40-59 years
      at recruitment into the Canadian National Breast Screening Study, a randomized
      controlled trial of mammography screening for breast cancer. During an average
      10.6 years of follow-up (936,433 person-years), a total of 527 women were
      diagnosed with incident colorectal cancer (363 colon and 164 rectal). We found
      that smoking was associated with increased risk of rectal cancer 30 years or more
      after commencement, and especially with smoking of 40 years' duration or longer
      (hazard ratio=3.14, 95% CI=1.33-7.42). There was little evidence for altered risk
      of colon cancer. These results, along with those of other recent studies, support
      the hypothesis that tobacco smoking is an initiator, rather than a promoter, of
      rectal cancer. However, the results do not support an association with colon
      cancer risk, even with smoking of very long duration and high intensity.

PMID- 11992464
TI  - Dual role for p75(NTR) signaling in survival and cell death: can intracellular
      mediators provide an explanation?
AB  - Several recent reports support a dual role of p75(NTR) in cell death, as well as
      survival, depending on the physiological or developmental stage of the cells.
      Coexpression of the TrkA receptor with p75(NTR) further enhances the complexity
      of nerve growth factor (NGF) signaling. Recent identification of serine/threonine
      kinases that interact with the p75(NTR) provides an explanation for the lack of
      an apparent kinase domain needed for signaling. In this report, we review the
      possible roles of the intracellular proteins that directly interact with the
      p75(NTR), atypical protein kinase C (PKC) binding protein, p62 and second
      messengers in the functional antagonism exhibited by TrkA and p75(NTR) with an
      emphasis on the nuclear factor-kappa B activation pathway.

PMID- 11992465
TI  - Video-microscopic analysis of dye coupling in the salamander olfactory bulb.
AB  - Cells in the mitral cell (MCL) and granule cell (GCL) layers of the olfactory
      bulb shape the representation of odor information in the brain. After
      intracellular Lucifer Yellow (LY) injections into lightly fixed olfactory bulb
      slices, clusters of dye coupled cells were previously observed in the MCL and
      GCL, but the relative extent of coupling in the two layers was unknown in adults.
      In the present study, the time course of LY coupling in the adult salamander
      olfactory bulb was quantified using video-microscopic methods. Analysis of
      fluorescent cell body counts showed that the incidence and the extent of LY
      coupling are greater in the GCL than in the MCL. With optimal low-current
      injection procedures, 97% of the injections into the GCL exhibited at least one
      coupled cell, and on average groups of six to eight cells were counted. Fewer
      injections into the MCL exhibited only one to three coupled cells. Some of these
      coupled cells were clearly mitral cells. No staining of cells was observed after
      extracellular LY injections, and intracellular injections of dextran dyes stained
      single cells, providing evidence that the LY coupled cells were stained through
      an intercellular route, presumably gap junctions. In live intact preparations,
      rapid LY staining of cell clusters was also observed using patch pipettes.
      Together, these results provide evidence that robust coupling occurs among
      olfactory bulb neurons in adults, which could have functional significance.

PMID- 11992466
TI  - Lectin-induced apoptosis of mature olfactory receptor cells.
AB  - Previous studies showed that uptake of the lectin conjugate, wheat germ
      agglutinin-horseradish peroxidase (WGA-HRP) by olfactory receptor cells results
      in a thinning of the olfactory epithelium (OE) and increased turnover of globose
      basal cells. To ascertain the cell-type lost as well as the time course and
      mechanism of the loss, the current study measured changes in the number of
      dendritic knobs, olfactory marker protein (OMP) expression and assessed TUNEL
      labeling as an indicator of apoptosis. Electron microscopic analysis of the
      number of dendritic knobs showed that the largest reduction occurred at 1 week
      after intranasal irrigation with WGA-HRP. This data in conjunction with decreased
      OMP staining provided evidence for a loss of mature receptor neurons. TUNEL
      labeling, especially in more superficial aspects of the OE, peaked at 18 hr after
      WGA-HRP application suggesting that the lectin-conjugate produced a rapid
      induction of apoptotic cell death that was complete by 3 days. Measurement of
      tyrosine hydroxylase (TH) activity in the olfactory bulb, a sensitive measure of
      deafferentation, showed that innervation reached a nadir at about 1 week and that
      reinnervation was complete by 4 weeks. These findings demonstrate that
      internalization of WGA-HRP by some receptor cells results in their death by
      apoptosis and a subsequent deafferentation of the olfactory bulb.

PMID- 11992467
TI  - DNA microarray analysis of the contused spinal cord: effect of NMDA receptor
      inhibition.
AB  - Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and
      devastating motor and sensory dysfunction. Post-traumatic outcomes are determined
      by events occurring during the first 24 hours after SCI. An increase in
      extracellular glutamate concentration to neurotoxic levels is one of the earliest
      events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322
      DNA probes) analysis to measure gene expression in order to test the hypothesis
      that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers
      significant postinjury transcriptional changes. Here we report that SCI, 1 hour
      after trauma, induced change in mRNA levels of 165 genes and expression sequence
      tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly
      transcription factors, inflammation, cell survival, and membrane excitability. We
      also report that NMDA receptor inhibition (with -(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate [MK-801]) reversed the
      effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is
      the finding that NMDA receptor activation participates in the up-regulation of
      inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of
      the dominant, early signals after trauma that leads to changes in mRNA levels of
      a number of genes relevant to recovery processes. The majority of MK-801 effects
      on the SCI-induced mRNA changes reported here are novel. Additionally, we found
      that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that
      had not been affected by SCI alone, and that some of their gene products could
      have harmful effects on SCI outcome.

PMID- 11992468
TI  - Chronic treatment with glutaric acid induces partial tolerance to excitotoxicity
      in neuronal cultures from chick embryo telencephalons.
AB  - Glutaryl-CoA dehydrogenase deficiency (GDD) is characterized biochemically by an
      accumulation of glutaric (GA) and 3-hydroxyglutaric (3-OH-GA) acids and
      clinically by the development of acute striatal degeneration. 3-OH-GA was
      recently shown to induce neuronal damage via N-methyl-D-aspartate (NMDA)
      receptors. The pathogenetic role of GA, however, remains unclear. We demonstrate
      that GA exerts a dual action in cultured chick embryo neurons. Short-term
      incubation with millimolar concentrations of GA induces a weak neuronal damage,
      adding to 3-OH-GA neurotoxicity. In contrast, chronic treatment with subtoxic,
      micromolar concentrations of GA results in partial tolerance to 3-OH-GA- and NMDA
      induced cell damage. A downregulation of NMDA receptors, in particular of the
      NR2B subunit, is critically involved in this GA-induced effect, resulting in a
      reduced Ca(2+) increase and generation of reactive oxygen species after acute
      exposure to NMDA or 3-OH-GA. Furthermore, GA decreases Na(+)/K(+)-ATPase
      activity, which is prevented by glutathione, suggesting a modulation of NMDA
      receptor function via resting membrane potential and Na(+)-dependent glutamate
      transport. In contrast, GA does not inhibit mitochondrial respiratory chain and
      beta-oxidation of fatty acids, virtually excluding an activation of NMDA
      receptors secondary to ATP depletion. These results strongly suggest that GA
      modulates the NMDA receptor-mediated neurotoxicity of 3-OH-GA, providing an
      explanatory basis for the non-linear relationship between organic acid
      concentrations and disease progression in GDD patients. Furthermore, GA-induced
      downregulation of NMDA receptors might be involved in the delayed cerebral
      maturation of GDD patients, resulting in frontotemporal atrophy and a reduced
      opercularization, which are common neuroradiological findings in GDD patients.

PMID- 11992469
TI  - Differences in peripheral nerve degeneration/regeneration between wild-type and
      neuronal nitric oxide synthase knockout mice.
AB  - Nitric oxide (NO), a unique biological messenger molecule, is synthesized by
      three isoforms of the enzyme NO synthase (NOS) and diffuses from the site of
      production across cellular membranes. A postulated role for NO in degeneration
      and regeneration of peripheral nerves has been explored in a sciatic nerve model
      comparing wild-type mice and mice lacking neuronal NOS after transection and
      microsurgical repair. In NOS knockout mice, regenerative delay was observed,
      preceded by a decelerated Wallerian degeneration (WD). In the regenerated nerve,
      pruning of uncontrolled sprouts was disturbed, leading to an enhanced number of
      axons, whereas remyelination seemed to be less affected. Delayed regeneration was
      associated with a delayed recovery of sensor and motor function. In such a
      context, possible NO targets are neurofilaments and myelin sheaths of the
      interrupted axon, filopodia of the growth cone, newly formed neuromuscular
      endplates, and Schwann cells in the distal nerve stump. The results presented
      suggest that 1) local release of NO following peripheral nerve injury is a
      crucial factor in degeneration/regeneration, 2) success of fiber regeneration in
      the peripheral nervous system depends on a regular WD, and 3) manipulation of NO
      supply may offer interesting therapeutic options for treatment of peripheral
      nerve lesions.

PMID- 11992470
TI  - Time course of polyglutamine aggregate body formation and cell death: enhanced
      growth in nucleus and an interval for cell death.
AB  - Polyglutamine (polyQ) aggregate bodies are a hallmark of dentatorubral
      pallidoluysian atrophy and related neurodegenerative disorders, although the
      relationship between aggregate body formation and cell death is not clear. We
      analyzed the kinetics of polyQ aggregate formation and the time intervals for
      cell death, tracking individual cells using fluorescence video microscopy, for
      the first time. Expanded polyQ tracts of atrophin-1 with or without nuclear
      localization signal (NLS) labeled with green fluorescent protein (GFP) were
      constructed, Q57NLS/GFP and Q56/GFP, respectively. All of the Q57NLS/GFP
      aggregate bodies were in nuclei, and all of the Q56/GFP aggregate bodies were in
      cytoplasm. Aggregates of Q56/GFP were larger than those of Q57NLS/GFP.
      Surprisingly, a kinetic analysis showed that the latter grew 5.37 times faster
      than the former. The time interval between transfection and cell death was
      shorter in Q57NLS/GFP, but the time between the end of the rapid growing phase of
      aggregation and the start of the cell death process did not show a significant
      difference. Aggregate growth was confirmed to correspond to the accumulated free
      polyQ by the time of starting aggregation. These findings suggest that aggregate
      body formation induced by expanded polyQ stretches is a self-limiting process and
      is enhanced by factor(s) in nuclei, whereas it is not tightly bound to the cell
      death process.

PMID- 11992471
TI  - Delta(9)-tetrahydrocannabinol increases endogenous extracellular glutamate levels
      in primary cultures of rat cerebral cortex neurons: involvement of CB(1)
      receptors.
AB  - The effects of the principal psychoactive component of marijuana, Delta(9)
      tetrahydrocannabinol (Delta(9)-THC), on endogenous extracellular glutamate levels
      in primary cultures of rat cerebral cortex neurons were investigated. Locally
      applied Delta(9)-THC (0.03, 3, 300, and 1,000 nM) concentration-dependently
      increased basal extracellular glutamate levels (+18% +/- 11%, +54% +/- 10%, +90%
      +/- 14%, +149% +/- 33% vs. basal). The facilitatory effects of Delta(9)-THC (3
      and 300 nM) on cortical glutamate were fully counteracted in the presence of the
      selective CB(1) receptor antagonist SR141716A (10 nM) and by replacement of the
      normal Krebs-Ringer bicarbonate buffer with a low-Ca(2+) (0.2 mM) medium.
      Delta(9)-THC application also induced an enhancement in K(+)-evoked glutamate
      levels. These findings suggest that an increase in cortical glutamatergic
      transmission mediated by local CB(1) receptor activation may underlie some of the
      psychoactive and behavioral effects of acute marijuana consumption.

PMID- 11992472
TI  - Ca(2+)-independent caspase-3 but not Ca(2+)-dependent caspase-2 activation
      induced by oxidative stress leads to SH-SY5Y human neuroblastoma cell apoptosis.
AB  - Continuous and long-lasting exposure to tert-butylhydroperoxide (t-BOOH)
      increased the number of apoptotic SH-SY5Y human neuroblastoma cells both in the
      presence and in the absence of the intracellular Ca(2+) ion chelator 1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). In addition, t-BOOH
      exposure induced activation of CPP32, as demonstrated by poly-(ADP-ribose)
      polymerase (PARP) cleavage, and of ICH-1L caspases. Exposure to t-BOOH also
      induced a time-dependent release of cytochrome c. Interestingly, in the presence
      of BAPTA, CPP32 activation still occurred, whereas ICH-1L activation was blocked.
      Ac-DEVD-CHO, an inhibitor of CPP32 activity, prevented the appearance of
      apoptotic cells, whereas the inhibitor of ICH-1L activity Z-VDVAD-FMK did not.
      Collectively, these findings demonstrate that in SH-SY5Y neuroblastoma cells
      exposure to continuous and long-lasting oxidative stress induced activation of
      caspase-3 that was independent of intracellular Ca(2+) ion concentration
      ([Ca(2+)](i)) elevation but led to cell apoptosis. In contrast, caspase-2
      activation was dependent on [Ca(2+)](i) increase but did not result in apoptosis.

PMID- 11992473
TI  - Neuroprotective effects of carnosine and homocarnosine on pheochromocytoma PC12
      cells exposed to ischemia.
AB  - The development of neuroprotective drugs against ischemic insults is hampered by
      the lack of pharmacological in vitro models. We developed an ischemic model using
      PC12 cell cultures exposed to oxygen-glucose-deprivation (OGD) followed by
      reoxygenation (18 hr) under regular atmospheric oxygen level. The toxicity
      induced in this model, that is partially caused by generation of reactive oxygen
      species (ROS), was measured morphologically as well as by the release of lactate
      dehydrogenase (LDH) and the prostaglandin PGE(2) from the cells. Carnosine and
      homocarnosine, histidine dipeptides antioxidants, found in high concentration in
      the brain, have been suggested to provide neuroprotection. Using the OGD model we
      found that 5 mM carnosine and 1 mM homocarnosine provided maximal neuroprotection
      of about 50% against OGD insult. This neuroprotective effect was similar to that
      of a known antioxidant, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol),
      and was not observed in a serum-deprivation toxicity model of PC12 cells,
      indicating that carnosine and homocarnosine may act as antioxidant
      neuroprotective agents in the brain. Our ischemic model may provide a useful tool
      for investigating the mechanisms involved in the neuroprotection afforded by
      histidine dipeptides.

PMID- 11992474
TI  - Extended action of MKC-242, a selective 5-HT(1A) receptor agonist, on light
      induced Per gene expression in the suprachiasmatic nucleus in mice.
AB  - We reported previously that (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]
      1,3-benzodioxole hydrochloride (MKC-242) (3 mg kg(-1), i.p.), a selective 5
      HT(1A) receptor agonist, accelerated the re-entrainment of hamster wheel-running
      rhythms to a new 8 hr delayed or advanced light-dark cycle, and also potentiated
      the phase advance of the wheel-running rhythm produced by light pulses. The
      molecular mechanism underlying MKC-242-induced potentiation of this phase shift,
      however, has not yet been elucidated. We examined the effects of MKC-242 on light
      induced mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus (SCN) of
      mice. MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced mPer1 and mPer2
      expression in the SCN of mice housed in constant darkness for 2 days, when mRNA
      levels were observed 3 hr after light-exposure. More potentiating action of MKC
      242 on mPer2 expression in the SCN was observed in mice housed in constant
      darkness for 9-10 days. This facilitatory action of MKC-242 on mPer1 expression
      was antagonized by WAY100635, a selective 5-HT(1A) receptor blocker, indicating
      that MKC-242 activated 5-HT(1A) receptors. Other drugs such as 8-hydroxy
      dipropylaminotetralin (10 mg kg(-1), i.p.), paroxetine (10 mg kg(-1), i.p.),
      buspirone (10 mg kg(-1), i.p.), and diazepam (10 mg kg(-1), i.p.) did not display
      a potentiating action on light-induced mPer1 and mPer2 expression in the SCN. In
      the behavioral experiments, we found that MKC-242 (5 mg kg(-1), i.p.) potentiated
      light-induced phase delays of free-running rhythm in mice. The present results
      suggest that prolonged increase of mPer1 or mPer2 expression in the SCN by MKC
      242 may be involved in the potentiation of photic entrainment by MKC-242 in mice.

PMID- 11992475
TI  - Effects of somatosensory cortical stimulation on expression of c-Fos in rat
      medullary dorsal horn in response to formalin-induced noxious stimulation.
AB  - We examined the effects of epidural electrical stimulation of primary (SI) and
      secondary (SII) somatosensory cortex on expression of c-Fos protein in rat
      medullary dorsal horn neurons (Vc; trigeminal nucleus caudalis) in response to
      formalin-induced noxious stimulation. Epidural electrical stimulation (single
      pulse, 0.2 msec duration at 10 Hz) was applied to the left facial region SI or
      SII at three different stimulus intensities, 0.1, 0.5, and 1.0 mA for 60 min 0 or
      2 hr after bilateral injection of formalin into the lower lip. SII stimulation at
      1.0 mA immediately after injection of formalin, significantly decreased the
      number of Fos-positive cells in the right VcI/II by 32.4%. There was no
      significant change in the number of Fos-positive cells in the VcIII/IV. SII
      stimulation at 0.5 and 1.0 mA 2 hr after injection of formalin, significantly
      decreased the number of Fos-positive cells in the right VcI/II by 47.9% and
      40.8%, but significantly increased the number of Fos-positive cells in the right
      VcIII/IV by 178.8% and 324.3%, respectively. In contrast, SI stimulation had no
      effect on expression of c-Fos in Vc. Possible direct corticotrigeminal
      projections were labeled anterogradely by injection of WGA-HRP into the SI and
      SII. In the Vc, labeled terminals were distributed mostly in the contralateral
      medial half of VcIII/IV and medullary reticular nucleus dorsalis but rarely in
      VcI/II. These results suggest that activation of SII-medullary fibers suppress
      nociceptive information from the oro-facial regions.

PMID- 11992476
TI  - GABA-B-related activity in processing of transcallosal response in cat motor
      cortex.
AB  - GABA-ergic characteristics of transcallosal (TC) responses were studied with
      specific antagonists of both GABA-A and GABA-B receptor subtypes. We used a
      paired-pulse paradigm to get insight into the role of GABA in interhemispheric
      interactions between motor cortices. 3-Amino-2-(4-chlorophenyl)-propylphosphonic
      acid (phaclofen) and 3-aminopropyl-diethoxymethyl-phosphinic acid (CGP 35348)
      were used as GABA-B antagonists and bicuculline methiodide (BMI) was used to
      block the GABA-A receptor. Although both GABA-A and GABA-B antagonists increased
      spike discharge upon transcallosal stimulation, in both pyramidal tract and non
      pyramidal tract neurons, they had different effects on the responses to the first
      and second stimuli of paired-pulse stimulation (200 msec interval). Although the
      inhibition seen with the second stimulus was greatly attenuated by antagonists of
      the GABA-B receptor, it was maintained in the presence of the GABA-A antagonist.
      These finding support a presynaptic regulation of callosal transmission by GABA-B
      receptors in the callosal synapse of the cat motor cortex.

PMID- 11992477
TI  - Evidence for a localization of [(3)H]nociceptin binding sites on medullar primary
      afferent fibers.
AB  - The ORL1 receptor (opioid receptor-like 1) and its endogenous ligand, nociceptin,
      are involved in nociperception. We have studied, in a deafferented animal model,
      the modification of medullar [(3)H]nociceptin binding site density. A rhizotomy
      was carried out in rats at the cervicothoracic level, and the dorsal afferent
      fibers from C5 to T1 were lesioned. Seven days after surgery, animals were
      sacrificed, and the binding of [(3)H]nociceptin (2 nM) was then performed on
      spinal cord sections. An autoradiographic analysis revealed a significant
      reduction (-18%) of [(3)H]nociceptin binding site density in the dorsal horn
      ipsilateral to the deafferentation compared with the contralateral side of the
      lesion. In the ventral horn, no significant difference (-5%) of binding was
      observed in the ipsilateral side of the deafferentation compared with the
      contralateral side. Thus, [(3)H]nociceptin binding sites appear to be located
      mainly on either interneurons or deutoneurons of the spinal cord, because the
      bulk of the labeling is spared by the lesion. However, the significant reduction
      of labeling that occurs on the dorsal part of the ipsilateral side to the lesion
      indicates that [(3)H]nociceptin binding sites are also present on these dorsal
      afferent fibers.

PMID- 11992478
TI  - New perspectives on the face in fetal alcohol syndrome: what anthropometry tells
      us.
AB  - Fetal alcohol syndrome (FAS) refers to the adverse effects to the fetus from
      prenatal exposure to alcohol. Originally, the diagnosis of FAS was given only to
      those individuals that were the most severely affected. Since that time, it has
      become apparent that the effects of prenatal alcohol exposure are broad-based,
      and those individuals diagnosed with FAS represent the severe end of the
      continuum in their phenotypic expression. This study utilized 21 craniofacial
      anthropometric measurements on 100 prenatally exposed individuals to quantify the
      elements of the FAS facial phenotype and to extend the quantitative phenotype to
      individuals who exhibited less severe or incomplete manifestations of prenatal
      alcohol exposure.

PMID- 11992479
TI  - Segregation of a novel FBN1 gene mutation, G1796E, with kyphoscoliosis and
      radiographic evidence of vertebral dysplasia in three generations.
AB  - Skeletal and spinal radiographic findings are described in five individuals of a
      three-generation kindred with kyphoscoliosis. The affected individuals have a
      novel FBN1 gene mutation, G1796E. To our knowledge, this is the first report of a
      family with an FBN1 gene mutation cosegregating with an unusual autosomal
      dominant progressive kyphoscoliosis of variable severity, together with
      radiological abnormalities of the spine, and some skeletal but no ocular or
      cardiac manifestations of Marfan syndrome. This previously undescribed phenotype
      represents yet another in the widening spectrum of fibrillinopathies caused by an
      FBN1 gene mutation.

PMID- 11992480
TI  - Micropenis with testicular regression, low LH levels, and poor androgen and HCG
      responses: a distinct syndrome?
AB  - We report three boys, including two brothers, with micropenis and poor phallic
      growth in response to both exogenous human chorionic gonadotropin (HCG) and
      testosterone therapy in the newborn period. They exhibited low neonatal
      testosterone levels that failed to respond to HCG stimulation. These boys
      displayed a unique gonadotropin profile with reduced luteinizing hormone levels
      and elevated follicle-stimulating hormone levels. They had small, cryptorchid
      testes with subsequent testicular regression and atrophy. Moreover, all three
      boys have developed microcephaly and mild learning delays. We review the hormonal
      profiles and phenotypes of known causes of micropenis, and compare them to the
      features of our three patients. Although individuals with similar features may
      have been described in past series of males with micropenis, the data presented
      previously were insufficient for classification; thus, we propose that our
      patients may represent a distinct, not previously recognized, syndrome with
      either X-linked recessive inheritance or autosomal recessive inheritance with
      male sex limitation.

PMID- 11992481
TI  - Polymorphism R25P in the gene encoding transforming growth factor-beta (TGF
      beta1) is a newly identified risk factor for proliferative diabetic retinopathy.
AB  - Associations of the genetic polymorphisms in the promoter region and the signal
      peptide sequence of the transforming growth factor-beta (TGF-beta1) gene with
      proliferative diabetic retinopathy (PDR) in patients with non-insulin-dependent
      diabetes mellitus (NIDDM) were studied. A total of 245 Caucasian subjects
      comprised the two groups: NIDDM patients with PDR (n = 73) and NIDDM patients
      without PDR (n = 172). Allele frequencies of common TGF-beta1 polymorphisms (at
      positions -988C/A, -800G/A, -509C/T, +869T/C (L10P), and +915G/C (R25P)) were
      determined by PCR-based methodology. All polymorphisms were in strong linkage
      disequilibrium (P < 10(-2)). Significantly higher frequencies of both the L
      allele and the R allele of the signal sequence polymorphisms in PDR subjects were
      found (after a correction for multiple comparisons, P(corr) < 10(-2) and P(corr)
      < 10(-4), respectively). Calculated odds ratios (ORs) for the LL and RR genotypes
      were 2.89 (95% confidence interval (CI), 1.6-5.1) and 19.73 (95% CI, 2.6-146.8),
      respectively. No significant differences between groups were found for the 
      800G/A and -509C/T polymorphisms. The -988A allele was not represented in our
      sample. Multiple logistic regression identified age, diabetes duration, and R25P
      polymorphism as significant predictors (P = 0.002, P = 0.000003, and P = 0.007,
      respectively). The frequencies of genotype combinations of the -800G/A, -509C/T,
      L10P, and R25P TGF-beta(1) polymorphisms were significantly different between the
      PDR and non-PDR groups (chi(2) = 37.83, df = 20, P < 10(-2)). The frequency of
      haplotype consisting of majority alleles was found significantly associated with
      PDR (P < 0.03). The presented data indicate that the R25P polymorphisms in the
      TGF-beta1 gene could be regarded as a strong genetic risk factor for PDR.

PMID- 11992482
TI  - Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos
      syndrome.
AB  - Skin hyperelasticity, tissue fragility with atrophic scars, and joint
      hypermobility are characteristic for the classical type of Ehlers-Danlos syndrome
      (EDS). The disease is usually inherited as an autosomal dominant trait; however,
      recessive mode of inheritance has been documented in tenascin-X-deficient EDS
      patients. Mutations in the genes coding for collagen alpha1(V) chain (COL5A1),
      collagen alpha2(V) chain (COL5A2), tenascin-X (TNX), and collagen alpha1(I) chain
      (COL1A1) have been characterized in patients with classical EDS, thus confirming
      the suspected genetic heterogeneity. Recently, we described a patient with severe
      classical EDS due to a Gly1489Glu substitution in the alpha1(V) triple-helical
      domain who was, in addition, heterozygous for a disease-modifying Gly530Ser
      substitution in the alpha1(V) NH(2)-terminal domain [Giunta and Steinmann, 2000:
      Am. J. Med. Genet. 90:72-79; Steinmann and Giunta, 2000: Am. J. Med. Genet.
      93:342]. Here, we report on a 4-year-old boy with mild classical EDS, born to
      healthy consanguineous Turkish parents; the mother presented a soft skin, while
      the father had a normal thick skin. Ultrastructural analysis of the dermis
      revealed in the patient the typical "cauliflower" collagen fibrils, while in both
      parents variable moderate aberrations were seen. Mutation revealed the presence
      of a homozygous Gly530Ser substitution in the alpha1(V) collagen chains in the
      patient, while both parents were heterozygous for the same substitution. An
      additional mutation in either the COL5A1 and COL5A2 genes was excluded.
      Furthermore, haplotype analysis with polymorphic microsatellite markers excluded
      linkage to the genes coding for alpha3(V) collagen (COL5A3), tenascin-X (TNX),
      thrombospondin-2 (THBS2), and decorin (DCN). These new findings support further
      our previous hypothesis that the heterozygous Gly530Ser substitution is disease
      modifying and now suggest that in the homozygous state it is disease causing.

PMID- 11992483
TI  - Searching for evidence of DFNB2.
AB  - Deafness is the most common form of sensory impairment in humans, affecting about
      1 in 1,000 births in the United States. Of those cases with genetic etiology,
      approximately 80% are nonsyndromic and recessively inherited. Mutations in
      several unconventional myosins, members of a large superfamily of actin
      associated molecular motors, have been found to cause hearing loss in both humans
      and mice. Mutations in the human unconventional Myosin VIIa (MYO7A), located at
      11q13.5, are reported to be responsible for both syndromic and nonsyndromic
      deafness. MYO7A mutations are responsible for Usher syndrome type Ib, the most
      common genetic subtype of Usher I. Usher I is clinically characterized by
      congenital profound deafness, progressive retinal degeneration called retinitis
      pigmentosa (RP), and vestibular areflexia. Although a wide spectrum of MYO7A
      mutations have been identified in Usher Ib patients, four mutations have been
      reported to cause DFNB2, a recessive deafness without retinal degeneration, and
      one mutation has been implicated in a single case of dominant nonsyndromic
      hearing loss (DFNA11). Our study attempts to ascertain additional DFNB2 families
      to investigate the disparate nonsyndromic phenotype and alleged causative
      mutations. Data from both linkage and heterogeneity analyses on 36 selected
      autosomal recessive nonsyndromic deafness (RNSD) families, all previously
      excluded by mutational analysis from GJB2 (Cx26), the leading cause of
      nonsyndromic deafness, showed no evidence of DFNB2 within the sample. These
      negative results and the isolated reports of DFNB2 bring into question whether
      certain MYO7A mutations produce nonsyndromic recessive hearing loss.

PMID- 11992484
TI  - Beta 1 integrin activation mediates adhesive differences between trisomy 21 and
      non-trisomic fibroblasts on type VI collagen.
AB  - Trisomy 21 (Down syndrome) is a common genetic condition with a high incidence of
      congenital heart defects (CHD), particularly those involving abnormal development
      of the embryonic atrioventricular (AV) canal. Type VI collagen (Col VI) is
      expressed in the developing AV canal extracellular matrix, and has been
      associated with trisomy 21 AV canal defects in human genetic studies. Although
      the molecular mechanisms linking Col VI and trisomy 21 AV canal defects are not
      well understood, a computer model predicts increased cell adhesiveness is
      responsible for these CHD. We compared integrin-mediated cell adhesive properties
      for skin fibroblasts isolated from trisomy 21 and non-trisomic individuals on Col
      VI, fibronectin (FN) and type I collagen (Col I). Cell lines demonstrate similar
      adhesion profiles to FN and Col I, but all trisomy 21 cells display increased
      adhesive capacity for Col VI compared to non-trisomic fibroblasts. Cell adhesion
      to type VI collagen was shown to be GRGDS independent, but beta(1) integrin
      family dependent. Function-blocking antibodies identified alpha(3)beta(1) as the
      predominant integrin mediating trisomy 21 and non-trisomic skin fibroblast
      adhesion on Col VI. Trisomy 21 and non-trisomic fibroblasts display similar
      expression levels for each of the integrin receptors examined. A beta(1) integrin
      activating antibody augments non-trisomic cell adhesion on Col VI, but has no
      effect upon trisomy 21 fibroblasts. These results demonstrate that beta(1)
      integrin family members mediate trisomy 21 and non-trisomic skin fibroblast
      adhesion for Col VI. Altered activation state of the beta(1) integrin is a
      mechanism responsible for increased trisomy 21 cell adhesion on Col VI.

PMID- 11992485
TI  - Phenotypic spectrum of interstitial 7p duplication in mosaic and non-mosaic
      forms.
AB  - The phenotypes of a mother and child with a duplication of 7p15-7p22 are
      described. The mother is mosaic for the cytogenetic abnormality, whereas all
      cells are affected in her son. Fewer than 5 patients with interstitial 7p
      duplications are described in the world literature whereas over 30 phenotypic
      descriptions of individuals with terminal 7p duplication can be found. Authors
      have suggested that the associated phenotype amounts to a recognizable syndrome.
      The current cases give further insights into the phenotype that results from pure
      7p duplication, both in its mosaic and in its full form. Comparisons are made
      with previous cases, in the light of the shorter segment involved in the current
      patients, whose duplication does not extend to pter. This case description will
      be useful in counseling patients with duplications of 7p and lends support to the
      existence of characteristic craniofacial features and congenital malformations in
      this chromosome rearrangement. In addition, as earlier case reports all describe
      the phenotype associated with non-mosaic partial 7p trisomy, the current
      observations amount to clear evidence that mosaicism attenuates the phenotype of
      this rearrangement.

PMID- 11992486
TI  - Familial complex chromosomal rearrangement resulting in a recombinant chromosome.
AB  - Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve
      fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We
      report on a CCR identified in a child with congenital heart disease and
      dysmorphic features. Initially, the child's karyotype was thought to involve a
      straightforward three-way translocation between chromosomes 3, 8, and 16.
      However, after analyzing the mother's chromosomes, the mother was found to have a
      more complex rearrangement that resulted in a recombinant chromosome in the
      child. The mother's karyotype included an inverted chromosome 2 and multiple
      translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or
      duplication that could account for the clinical findings in the child was
      identified.

PMID- 11992487
TI  - Spondylocarpotarsal synostosis with epiphyseal dysplasia.
AB  - We report on an 11-year-old boy with thoracolumbar fusion, carpal synostosis,
      short stature, scoliosis, lordosis, defective dentition, and recurrent otitis
      media consistent with the diagnosis of spondylocarpotarsal synostosis syndrome.
      Unlike other documented cases, radiographs of our patient at 5(1/2) years of age
      show delay in ossification of many of the epiphyses in addition to delay in
      carpal ossification. Such delay may have contributed to the distinctly short
      stature of this boy. This report both confirms and extends the phenotype of this
      recently delineated syndrome.

PMID- 11992488
TI  - Craniosynostosis, telecanthus, scalp hair abnormalities, and sensorineural
      deafness in two sibs.
AB  - A sister and a brother with anomalous skull configuration, facial abnormalities,
      abnormal scalp hair growth, sensorineural hearing loss and, in the boy, proven
      craniosynostosis, severe mental retardation, and autism were reported in 1986 in
      an abstract by Hersh et al. We reexamined this family and here review the
      literature focusing on the major clinical findings, and suggest that their
      clinical manifestations may represent a previously unreported syndrome.

PMID- 11992489
TI  - Variant Gaucher disease characterized by dysmorphic features, absence of
      cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel
      mutation (D409H/C16S).
AB  - A 20-month-old girl with developmental delay, dysmorphic features, horizontal
      supranuclear gaze palsy, retrocollis, and episodes of laryngospasm was diagnosed
      with variant neuronopathic Gaucher disease. The diagnosis was made enzymatically.
      Mutation analysis showed compound heterozygosity for D409H and a previously
      unreported mutation C16S. The presence of dysmorphic features, laryngospasm,
      absent cardiac findings, and the severe clinical phenotype distinguishes our case
      from other cases of variant neuronopathic Gaucher disease. We therefore propose
      to extend the spectrum of variant Gaucher disease.

PMID- 11992490
TI  - Joubert syndrome: more than lower cerebellar vermis hypoplasia, less than a
      complex brain malformation.

PMID- 11992491
TI  - Poland anomaly with foot symbrachydactyly.

PMID- 11992492
TI  - Increased nuchal translucency in the first trimester as a sign of osteogenesis
      imperfecta.

PMID- 11992493
TI  - Meier-Gorlin syndrome.

PMID- 11992495
TI  - Combined cuff and suture technique for orthotopic whole intestinal
      transplantation in rats.
AB  - For the purpose of immunological study on small intestinal transplantation (SIT),
      rat SIT models using direct suture technique widely have been used, which
      requires at least several months of training for microsurgery. Alternatively, a
      simple cuff technique for SIT has been mainly used by us, which reduces warm
      ischemic time and the training period, but the entire intestinal grafts usually
      obtain a limited blood supply. This report describes a modification of a combined
      cuff and suture technique for rat SIT to aid beginning microsurgical
      transplantation researchers. The advantages are 1) use of only arterial suturing,
      making it easier for beginners, with the cuff technique applied to the more
      difficult vein anastomosis; 2) achievement of better arterial inflow and graft
      survival than when the arterial cuff technique is used; and 3) doing only partial
      clamping of the aorta, which improves animal survival and success of the
      procedure. A very high successful rate in orthotopic whole SIT was achieved even
      by beginners.

PMID- 11992496
TI  - Anterior versus posterior approach in reconstruction of infected nonunion of the
      tibia using the vascularized fibular graft: potentialities and limitations.
AB  - The potentialities, limitations, and technical pitfalls of the vascularized
      fibular grafting in infected nonunions of the tibia are outlined on the basis of
      14 patients approached anteriorly or posteriorly. An infected nonunion of the
      tibia together with a large exposed area over the shin of the tibia is better
      approached anteriorly. The anastomosis is placed in an end-to-end or end-to-side
      fashion onto the anterior tibial vessels. To locate the site of the nonunion, the
      tibialis anterior muscle should be retracted laterally and the proximal and
      distal ends of the site of the nonunion debrided up to healthy bleeding bone. All
      the scarred skin over the anterior tibia should be excised, because it becomes
      devitalized as a result of the exposure. To cover the exposed area, the fibula
      has to be harvested with a large skin paddle, incorporating the first
      septocutaneous branch originating from the peroneal vessels before they gain the
      upper end of the flexor hallucis longus muscle. A disadvantage of harvesting the
      free fibula together with a skin paddle is that its pedicle is short. The skin
      paddle lies at the antimesenteric border of the graft, the site of incising and
      stripping the periosteum. In addition, it has to be sutured to the skin at the
      recipient site, so the soft tissues (together with the peroneal vessels), cannot
      be stripped off the graft to prolong its pedicle. Vein grafts should be resorted
      to, if the pedicle does not reach a healthy segment of the anterior tibial
      vessels. Defects with limited exposed areas of skin, especially in questionable
      patency of the vessels of the leg, require primarily a fibula with a long pedicle
      that could easily reach the popliteal vessels and are thus better approached
      posteriorly. In this approach, the site of the nonunion is exposed medial to the
      flexor digitorum muscle and the proximal and distal ends of the site of the
      nonunion debrided up to healthy bleeding bone. No attempt should be made to strip
      the scarred skin off the anterior aspect of the bone lest it should become
      devitalized. Any exposed bone on the anterior aspect should be left to granulate
      alone. This occurs readily when stability has been regained at the fracture site
      after transfer of the free fibula. The popliteal and posterior tibial vessels are
      exposed, and the microvascular anastomosis placed in an end-to-side fashion onto
      either of them, depending on the length of the pedicle and the condition of the
      vessels themselves. To obtain the maximal length of the pedicle of the graft, the
      proximal osteotomy is placed at the neck of the fibula after decompressing the
      peroneal nerve. The distal osteotomy is placed as distally as possible. After
      detaching the fibula from the donor site, the proximal part of the graft is
      stripped subperiosteally, osteotomized, and discarded. Thus, a relatively long
      pedicle could be obtained. To facilitate subperiosteal stripping, the free fibula
      is harvested without a skin paddle. In this way, the use of a vein graft could be
      avoided. Patients presenting with infected nonunions of the tibia with extensive
      scarring of the lower extremity, excessively large areas of skin loss, and with
      questionable patency of the anterior and posterior tibial vessels are not
      suitable candidates for the free vascularized fibular graft. Although a vein
      graft could be used between the recipient popliteal and the donor peroneal
      vessels, its use decreases flow to the graft considerably. These patients are
      better candidates for the Ilizarov bone transport method with or without free
      latissimus dorsi transfer.

PMID- 11992497
TI  - In vivo measurement of oxygen-derived free radicals during reperfusion injury.
AB  - By use of an optimized cytochrome c-based biosensor, superoxide radical
      production was measured continuously in vivo. The aim of this study was the
      online detection of superoxide concentration during reperfusion after a variable
      time of ischemia. Measurements were performed by placing the detecting sensor
      into gastrocnemius muscle tissue. Ischemia was induced by clamping the vena and
      arteria femoralis. Current response of the sensor was recorded continuously as an
      equivalent for superoxide concentration. Ischemia times varied from 5 to 120
      minutes. The minimum ischemia time to record superoxide production was 10
      minutes. By inducing longer periods of ischemia, an increase in superoxide
      concentration reached its highest levels at 2 hours. Furthermore, the total time
      of superoxide production after reperfusion depended on the total time of
      ischemia.

PMID- 11992498
TI  - Vascularized composite tissue transfers or open fractures with massive soft
      tissue defects in the lower extremities.
AB  - From 1982 to 1998, we treated 39 patients with type IIIB and IIIC fractures in
      the lower extremities by vascularized composite tissue transfers. Thirty-four of
      the lesions affected the lower leg, and 5 the foot and ankle. The peroneal flap
      was used in 25 cases, the latissimus dorsi musculocutaneous flap in 12, the
      scapula flap in 1, and the gracilis muscle flap in 1. In cases with a peroneal
      flap transfer, 18 cases used osteocutaneous flap with a fibula. Postoperative
      circulatory disturbances resulted in revision surgery in 9 patients. Eventually,
      grafting was successful in 37 patients. In patients with a lower leg
      reconstruction, additional bone grafting was performed in 7 of 16 patients with
      cutaneous or musculocutaneous flap transfers. No patient with osteocutaneous flap
      transfers required an additional bone grafting. The mean periods between injury
      and time to bone union were 11.7 months in patients with cutaneous flap
      transfers, and 7.5 months in patients with osteocutaneous flap transfers.

PMID- 11992500
TI  - End-to-side neurorrhaphy.
AB  - End-to-side neurorrhaphy, a possible strategy for treating nerve lesions without
      useable proximal nerve stumps, has been experimentally and clinically
      investigated. In end-to-side neurorrhaphy, three main elements should be
      considered: 1) the induction of axonal collateral sprouting in the donor nerve;
      2) the ability of the collateral axons to pierce the different conjunctival
      layers, including the ability the donor nerve basal laminae, to reinnervate the
      recipient nerve; and 3) the functional plasticity and behavioral readjustment of
      single motoneurons that have eventually adopted new motor units. This article
      reviews the following areas of research and clinical investigation: animal
      models, axonal collateral sprouting from end-to-side neurorrhaphy, effect of
      epineurotomy and perineurotomy on axon regeneration, motor reinnervation, and
      clinical trials.

PMID- 11992501
TI  - Solid-phase derivatization of tryptic peptides for rapid protein identification
      by matrix-assisted laser desorption/ionization mass spectrometry.
AB  - Solid-phase sulfonation of tryptic peptides adsorbed to C18 muZipTips has been
      carried out to facilitate de novo sequencing with mass spectrometry. Peptides are
      reacted with the sulfonation reagent while they are still adsorbed to the solid
      phase. Excess reagent passes through the ZipTip to waste. Washing the products
      before subsequent elution from the mini-column also affords sample cleanup prior
      to analysis. Near quantitative N-terminal sulfonation can be achieved reliably at
      room temperature in only a few seconds. The method has been applied successfully
      to model peptides and to solution or in-gel digests of proteins. Current
      sequencing limits are about 100 fmol of protein. Multiplexed sample sulfonation
      reactions have been carried out with a manual 8-position micropipettor or using
      centrifugal force to reliably pass reagents and wash solutions over sample-loaded
      ZipTips. With multiplexing, overall preparation times have been reduced to about
      1 min per sample. The solid-phase format facilitates efficient use of precious
      digest samples by enabling them to be recovered from the matrix-assisted laser
      desorption/ionization (MALDI) sample stage after mass fingerprinting, derivatized
      and re-analyzed by MALDI postsource decay mass spectrometry.

PMID- 11992503
TI  - MS3 using the collision cell of a tandem mass spectrometer system.
AB  - We report the feasibility of multistage fragmentation in combination with a fast
      background subtraction method, yielding the equivalent of MS3. The first
      quadrupole selects an ion of interest, and the ion is axially accelerated into Q2
      to generate fragment ions. Subsequent stages of mass selection and fragmentation
      are obtained by quadrupolar resonant excitation within the Q2 collision cell. The
      fragments are analyzed downstream by either a resolving quadrupole or a time-of
      flight (TOF) mass spectrometer, and multistage spectra are obtained by
      subtraction (MS(n) - MS(n-1)) for n = 3 or 4. We discuss the characterization of
      this method, including product ion arrival times, fragmentation efficiencies, and
      ion selectivity. We report accurate TOF mass spectra of background-subtracted MS3
      for protonated molecules reserpine (m/z 609), bosentan (m/z 1552), and taxol (m/z
      854).

PMID- 11992504
TI  - Electrospray ionization tandem mass spectrometric characteristics and
      fragmentation mechanisms of distamycin analogues.
AB  - The electrospray ionization tandem mass spectrometric (ESI-MS/MS) characteristics
      and fragmentation mechanisms of eight distamycin analogues containing N
      methylpyrrole and N-methylimidazole were investigated. The members of two
      isomeric groups of distamycin analogues with the same elemental composition can
      be distinguished by MS/MS spectra of protonated molecules and of significant
      fragment ions.

PMID- 11992505
TI  - Sequencing wasp venom peptides by endopeptidase digestion and nested collision
      induced dissociation/post-source decay methods.
AB  - A method incorporating nested collision-induced dissociation/post-source decay
      (CID/PSD) combined with endopeptidase digestion is described as an approach to
      determine the sequence of N-terminally modified peptides. The information from
      immonium and related ions observed in the CID/PSD spectrum was used for the
      selection of a suitable endopeptidase for the digestion of peptides. Rapid and
      reliable assignment of peptide sequence was performed by the comparison of
      CID/PSD spectra of both intact and endopeptidese-digested peptide fragments,
      since the assignments of the observed fragment ions to either N- or C-terminal
      ions can thus be carried out unambiguously. This nested CID/PSD method was
      applied to the sequence determination of two peptides from the solitary wasps
      Anoplius samariensis and Batozonellus maculifrons (pompilid wasps), which could
      not be sequenced by the Edman method due to N-terminal modification.

PMID- 11992506
TI  - Homocysteine thiolactone and protein homocysteinylation: mechanistic studies with
      model peptides and proteins.
AB  - In vitro incubations were performed to show that homocysteine thiolactone could
      generate covalent adducts with model peptides and proteins. MS and MS/MS data
      suggest that the thiolactone reacts with the side-chain amino group of lysine
      residues as well as with the N-terminal amino group or C-terminal carboxy group.
      For larger peptides and proteins, the contribution from the in-amino groups of
      lysine residues should be predominant. These data could help explain the
      detrimental effects of elevated levels of homocysteine and homocysteine
      thiolactone.

PMID- 11992507
TI  - Differential isotopic mass splitting as a mass spectrometric tool for identifying
      protease substrates.
AB  - A method is described whereby stable isotopic signatures were partially
      incorporated into both termini of a peptide sequence giving rise to a
      characteristic cluster of four peaks in the mass spectral analysis. Cleavage of
      this peptide by a protease between the labeled positions generates two fragments
      both displaying their own individual signature peaks. The event of protease
      cleavage of the peptide was monitored by the changes in clusters within the
      spectrum. We believe that this technique could be used to aid the discovery of
      new cleavage substrates for proteases. Additionally, the analysis can be
      automated with dedicated software designed to select and interpret the data since
      all peaks of interest contain predefined signatures and can be easily
      distinguished from background noise.

PMID- 11992508
TI  - On-line measurement of intramolecular carbon isotope distribution of acetic acid
      by continuous-flow isotope ratio mass spectrometry.
AB  - Molecular and intramolecular carbon isotope measurements of acetic acid present
      in natural environments have been performed by off-line procedures. The off-line
      method is complicated and time-consuming and requires micromolar to millimolar
      amounts of sample. This limits geochemical isotopic studies, especially at the
      intramolecular level, on acetic acid present in natural samples. Here, we examine
      an on-line measurement of intramolecular carbon isotope distribution of acetic
      acid using continuous-flow isotope ratio mass spectrometry (CF-IRMS) coupled with
      an on-line pyrolysis system. This is achieved by measurement of the respective
      carbon isotope ratios of CH4 and CO2 produced by on-line pyrolysis of acetic
      acid. Results for authentic standards of pure acetic acid demonstrated the
      practicality of this on-line method, although the carbon isotope ratio of the
      methyl group could not be determined directly. The precision of the carbon
      isotope measurements was 0.4 per thousand (1sigma). The carbon isotope
      distribution determined by the on-line method was identical to that determined by
      the conventional off-line method within analytical error. The advantages of the
      on-line method compared with the conventional off-line method are that it is less
      laborious, requires less analytical time (less than one hour per sample) and,
      most importantly, uses smaller sample sizes (ca. 10 nanomole). An application of
      this on-line method to natural geochemical samples will provide an insight into
      the geochemical cycle of acetic acid.

PMID- 11992509
TI  - Determination of drug concentrations in plasma by a highly automated, generic and
      flexible protein precipitation and liquid chromatography/tandem mass spectrometry
      method applicable to the drug discovery environment.
AB  - This report presents a highly automated procedure for the determination of drug
      concentrations in plasma samples. The method is generic, in that it has been
      applied without adaptation to many different drug candidate molecules, but is
      also flexible, in that variations in the nature and number of samples to be
      analyzed can be readily accommodated. The method includes preparation of
      dilutions of analyte stock solutions, spiking these into control plasma to
      generate analytical standards, and preparation of samples suitable for analysis
      by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS)
      by precipitation of plasma proteins with acetonitrile, centrifugation, and
      dilution of the supernatants with HPLC buffer. All of these steps, apart from
      centrifugation, are performed without manual intervention on an automated liquid
      handling workstation using 96-well plates. Analysis is by HPLC/MS/MS, using a
      generic HPLC gradient. Commercially available software was used for optimization
      of parameters for analysis by HPLC/MS/MS, integration of chromatographic peaks,
      and quantification of drug concentrations. The use of this methodology in our
      laboratory has greatly facilitated the analysis of small sample sets for a large
      number of analytes, a situation regularly encountered in an early drug discovery
      environment.

PMID- 11992510
TI  - Influence of the eluent composition on the ionization efficiency for morphine of
      pneumatically assisted electrospray, atmospheric-pressure chemical ionization and
      sonic spray.
AB  - A comparative study of three atmospheric-pressure ionization (API) sources for
      liquid chromatography/mass spectrometry (LC/MS), namely pneumatically assisted
      electrospray or ionspray (IS), atmospheric-pressure chemical ionization (APCI),
      and sonic spray (SS), with respect to the influence of the eluent composition on
      the ionization of morphine, is presented. The effect of organic modifiers,
      volatile acids, and buffer systems (with and without pH adjustment) in the LC
      mobile phase on the ionization efficiency of each interface is described. We
      conclude that for all three ion sources, the composition of the liquid phase had
      a serious impact on the ionization of the target compound. For IS and SS, very
      similar behavior towards the LC eluent was observed. In both cases, an increase
      in organic modifier resulted in an increase in ionization, while an increasing
      amount of volatile acid or buffer caused signal suppression. APCI, on the other
      hand, proved to respond completely differently towards the changes in the eluent.
      Again, an increased ionization was observed with an increase in organic modifier
      content but this time also in the presence of mobile phase additives like acids
      or buffers. Finally, we concluded that APCI proved to be the preferred ion source
      for the test compound because of its robust character and its direct
      applicability in traditional LC analysis.

PMID- 11992511
TI  - Characterizing the fragmentation of 2,5-bis (4-amidinophenyl)furan-bis-O
      methylamidoxime and selected metabolites using ion trap mass spectrometry.
AB  - A novel prodrug [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime (DB289)] of
      the promising antimicrobial agent, 2,5-bis(4-amidinophenyl)furan (DB75), has
      excellent oral activity. It is currently undergoing phase II clinical evaluation
      as an orally administered drug candidate against African trypanosomiasis and
      Pneumocystis carinii pneumonia. The sequential product ion (MS(n)) fragmentations
      of DB289 and selected metabolites were characterized using ion trap mass
      spectrometry with electrospray ionization. An unusual homolytic bond cleavage,
      formation of an odd-electron ion from an even-electron ion with the loss of a
      radical, was commonly seen in the fragmentation patterns of DB289 and its
      metabolites. Both O-ethyl and N-methyl homologues of DB289 were utilized to
      confirm this fragmentation pathway. The labile hydrogen atoms in DB289 are
      readily exchanged with deuterium atoms in the solvent containing deuterium oxide
      (D2O) instead of water. The mass shift patterns displayed in the product ion
      spectra of DB289 in D2O proved useful in verifying the fragmentation pathway.
      Octadeuterated DB289 and DB75 (d-labeling on the diphenyl rings) showed
      unequivocally that the diphenylfuran moiety is not involved in the fragmentation.
      The fragmentation pathways uncovered in this work will facilitate structural
      characterization of all the metabolites produced in the metabolic activation of
      DB289.

PMID- 11992512
TI  - Headspace solid-phase microextraction gas chromatography/mass spectrometry in the
      analysis of the aroma constituents of 'Cannonau of Jerzu' wine.
AB  - "Cannonau of Jerzu" wine is a typical Sardinian product, obtained from only one
      particular grape variety. Its aroma profile is highly characteristic from the
      organoleptic point of view but, until now, no analytical investigation of the
      aroma components has been reported. This aspect has been studied by headspace
      solid-phase microextraction coupled with gas chromatography/mass spectrometry
      (GC/MS). Using this approach, 76 abundant aroma components were identified. The
      results thus obtained show on one hand that the terpene profile is, as expected,
      dependent on the quality of the grapes (in terms of selection before vintage),
      and, on the other, that some components are strongly dependent on the production
      and ageing method.

PMID- 11992513
TI  - Novel direct detection method for quantitative determination of intracellular
      nucleoside triphosphates using weak anion exchange liquid chromatography/tandem
      mass spectrometry.
AB  - A novel analytical method has been developed for direct quantification of
      intracellular nucleoside triphosphates (NTPs). Lysates of human peripheral blood
      mononuclear cells (PBMCs) were extracted by protein precipitation, and the
      filtered extracts were analyzed by weak anion exchange liquid chromatography (WAX
      LC) coupled to detection by mass spectrometry (MS). Compared with ion pairing
      (IP)-LC/MS/MS, the only MS-compatible direct detection method for NTPs currently
      available, the new method completely avoids the usage of ion-pairing reagents and
      has a shorter analytical time of only 2 min. The method was validated and is
      being used to determine the amount of the triphosphate metabolite of D-D4FC
      (DPC817), an investigational HIV nucleoside reverse transcriptase inhibitor
      (NRTI), in human PBMC samples from clinical studies. By using a PE Sciex API 4000
      triple quadrupole instrument operating in positive ion MRM mode, the method was
      able to achieve a lower limit of quantitation (LLOQ) of 5 fmol/10(6) cells in
      samples containing 3 x 10(6) lysed cells (6 fmol on-column). With minor
      adaptation, the method described here may be suitable for analyzing other NTPs.
      This paper also provides a discussion of the unique retention characteristics of
      WAX-LC, the principles of which may prove to be valuable for designing other
      forms of directly coupled ion-exchange (IX)-LC/MS methods suited for high
      sensitivity quantitative analysis.

PMID- 11992515
TI  - Application to routine analysis of a method to determine multiclass pesticide
      residues in fresh vegetables by gas chromatography/tandem mass spectrometry.
AB  - The use of gas chromatography/tandem mass spectrometry (GC/MS/MS) applied to
      determine multiple pesticide residues in fresh vegetables has been thoroughly
      studied. A single injection method to detect, confirm and quantify 54 multiclass
      pesticides has been developed and applied in a routine analysis laboratory. The
      proposed method consists of a rapid extraction of 15 g of vegetable sample with
      dichloromethane. An additional clean-up step is not necessary even when injecting
      10 microL of extract. Instead the gas chromatograph was fitted with a carbofrit
      inserted into the glass liner and a guard column. In addition, the detection mode
      chosen (MS/MS) provides additional selectivity. The method has been validated and
      applied to 1300 samples in a routine laboratory following specified quality
      criteria. The recovery efficiencies obtained for all the pesticides ranged
      between 70.2 and 110.8% at two different fortification levels. The relative
      standard deviation for quantification (RSD) was lower than 16.7% for all the
      compounds. Important experimental parameters, such as the conditioning of
      carbofrit, overload of the analytical column, and cleanliness of the ion trap,
      were evaluated for their influence on the performance of the method.

PMID- 11992516
TI  - High-speed gradient parallel liquid chromatography/tandem mass spectrometry with
      fully automated sample preparation for bioanalysis: 30 seconds per sample from
      plasma.
AB  - In this work, a high-throughput and high-performance bioanalytical system is
      described that is capable of extracting and analyzing 1152 plasma samples within
      10 hours. A Zymark track robot system interfaced with a Tecan Genesis liquid
      handler was used for simultaneous solid-phase extraction of four 96-well plates
      in a fully automated fashion. The extracted plasma samples were injected onto
      four parallel monolithic columns for separation via a four-injector autosampler.
      The use of monolithic columns allowed for fast and well-resolved separations at a
      considerably higher flow rate without generating significant column backpressure.
      This resulted in a total chromatographic run cycle time of 2 min on each 4.6 x
      100 mm column using gradient elution. The effluent from the four columns was
      directed to a triple quadrupole mass spectrometer equipped with an indexed four
      probe electrospray ionization source (Micromass MUX interface). Hence, sample
      extraction, separation, and detection were all performed in a four-channel
      parallel format that resulted in an overall throughput of about 30 s per sample
      from plasma. The performance of this system was evaluated by extracting and by
      analyzing twelve 96-well plates (1152) of human plasma samples spiked with
      oxazepam at different concentrations. The relative standard deviation (RSD) of
      analyte sensitivity (slope of calibration curve) across the four channels and
      across the 12 plates was 5.2 and 6.8%, respectively. An average extraction
      recovery of 77.6% with a RSD of 7.7% and an average matrix effect of 0.95 with a
      RSD of 5.2% were achieved using these generic extraction and separation
      conditions. The good separation efficiency provided by this system allowed for
      rapid method development of an assay quantifying the drug candidate and its close
      structural analog metabolite. The method was cross-validated with a conventional
      liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay.

PMID- 11992517
TI  - Analysis of petrol and diesel vapour and vehicle engine exhaust gases using
      selected ion flow tube mass spectrometry.
AB  - We have used selected ion flow tube mass spectrometry (SIFT-MS) to analyse the
      vapours emitted by petrol and diesel fuels and the exhaust gases from petrol
      (spark ignition) and diesel (compression ignition) engine vehicles fitted with
      catalytic converters. Only those components of these media that have significant
      vapour pressures at ambient temperatures were analysed and thus particulates were
      obviously not detected. These media have been analysed using the full scope of
      SIFT-MS, i.e., with the three available precursor ions H3O+, NO+ and O2+. The
      combination of the H3O+ and NO+ analyses is seen to be essential to distinguish
      between different product ions at the same mass-to-charge ratio (m/z) especially
      in identifying aldehydes in the exhaust gases. The O2+ precursor ions are used to
      detect and quantify the large amount of nitric oxide present in the exhaust gases
      from both engine types. The petrol and diesel vapours consist almost exclusively
      of aliphatic alkanes, alkenes and alkynes (and dienes) and aromatic hydrocarbons.
      Some of these compounds appear in the exhaust gases together with several
      aldehydes, viz. formaldehyde, acetaldehyde, pentanal, pentenal (acrolein),
      butenal, and also methanol and ethanol. Acetone, nitric oxide and ammonia are
      also present, acetone and nitric oxide being much more abundant in the diesel
      exhaust gas than in the petrol exhaust gas. These data were obtained from samples
      collected into pre-evacuated stainless steel vessels. Trapping of the volatile
      compounds from the gas samples is not required and analysis was completed a few
      minutes later. All the above compounds are detected simultaneously, which
      demonstrates the value of SIFT-MS in this area of research.

PMID- 11992518
TI  - Larval electroreceptors in the epidermis of mormyrid fish: I. Tuberous organs of
      type A and B.
AB  - Two types of larval electroreceptors, type A and B, are described in the
      epidermis of the head of larvae of three mormyrid species, Campylomormyrus
      cassaicus, Mormyrus rume proboscirostris and Pollimyrus isidori, bred in
      captivity. In each of these electroreceptor organs, a single sensory cell is
      found inside an intraepidermal cavity, sitting on a platform of accessory cells.
      The cavity is filled with microvilli originating both from the sensory cell and
      from the epidermal covering cells lining the intraepidermal cavity. These two
      types of tuberous larval electroreceptors differ in their distribution in the
      epidermis of the head, in the composition of their accessory cells, and by their
      innervation. The innervation found in type B organs is similar to that already
      described for electroreceptors of adult mormyrids. The sensorineural junction is
      composed of primary afferent terminal boutons, which contact the base of the
      sensory cell. Opposite each terminal bouton, a ribbon-like synaptic bar
      surrounded by vesicles is found in the cytoplasm of the sensory cell. In
      contrast, the base of the sensory cell in type A larval electroreceptors is not
      contacted by nervous terminal boutons, but instead forms closed appositions with
      specialized prolongations of accessory cells of the platform. The base of the
      sensory cell presents membrane evaginations, with hemispheric synaptic structures
      and few synaptic vesicles. These two types of electroreceptor organs degenerate
      at the time of the degeneration of the larval electric organ and the functional
      differentiation of the adult electric organ. The functional role of two tuberous
      electroreceptor types is examined.

PMID- 11992519
TI  - Distribution of two splice variants of the glutamate transporter GLT-1 in the
      developing rat retina.
AB  - The distributions of a carboxyl terminal splice variant of the glutamate
      transporter GLT-1, referred to as GLT-1B, and the carboxyl terminus of the
      originally described variant of GLT-1, referred to hereafter as GLT-1 alpha, were
      examined using specific antisera. GLT-1B was present in the retina at very early
      developmental stages. Labelling was demonstrable at embryonic day 14, and strong
      labelling was evident by embryonic day 18. Such labelling was initially
      restricted to populations of cone photoreceptors, the processes of which extended
      through the entire thickness of the retina and appeared to make contact with the
      retinal ganglion cells. During postnatal development the GLT-1B-positive
      photoreceptor processes retracted to form the outer plexiform layer, and around
      postnatal day 7, GLT-1B-immunoreactive bipolar cells appeared. The pattern of
      labelling of bipolar cell processes within the inner plexiform layer changed
      during postnatal development. Two strata of strongly immunoreactive terminals
      were initially evident in the inner plexiform layer, but by adulthood these two
      bands were no longer evident and labelling was restricted to the somata and
      processes (but not synaptic terminals) of the bipolar cells, as well as the
      somata, processes, and terminals of cone photoreceptors. By contrast, GLT-1 alpha
      appeared late in postnatal development and was restricted mainly to a population
      of amacrine cells, although transient labelling was also associated with punctate
      elements in the outer plexiform layer, which may represent photoreceptor
      terminals.

PMID- 11992520
TI  - Firing features and potassium channel content of murine spiral ganglion neurons
      vary with cochlear location.
AB  - Neurons from varied regions of the central nervous system can show widely
      divergent responses to electrical stimuli that are determined by cell-specific
      differences in ion channel composition. The well-ordered and highly characterized
      peripheral auditory system allows one to explore the significance of this
      diversity during the final stages of postnatal development. We examined the
      electrophysiological features of murine spiral ganglion neurons in vitro at a
      time when recordings could be made from the cell bodies before myelination. These
      cells carry information about sound stimuli from hair cell receptors in the
      basilar membrane and are arranged tonotopically. Spiral ganglion neuron responses
      to depolarizing current injection were assessed with whole-cell current clamp
      recordings from cells that were isolated separately from the apical and basal
      thirds of the mouse cochlea. These cells displayed systematic variation in their
      firing. Apex neurons (low frequency coding) showed longer latency, slowly
      adapting responses, whereas base neurons (high frequency coding) showed short
      latency, rapidly adapting responses to the same stimuli. This physiological
      diversity was mirrored by regional differences in ion channel content assessed
      immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits,
      whereas base neurons possessed greater levels of K(Ca), Kv1.1, and Kv3.1
      subunits. Taken together, these results indicate that the distribution of a set
      of voltage-gated potassium channels may relate specifically to a particular range
      of coding frequencies. These studies also suggest that intrinsic properties of
      spiral ganglion neurons can contribute to the characteristic responses of the
      peripheral auditory system. Their potential role in development and adult
      function is discussed.

PMID- 11992521
TI  - Monoaminergic and peptidergic axonal projections to the vagal motor cell column
      of a teleost, the filefish Stephanolepis cirrhifer.
AB  - In an immunohistochemical study, the vagal motor nucleus of a teleost, the
      filefish Stephanolepis cirrhifer, could be divided into a rostral part and a
      caudal part, and the former into a dorsolateral group and a ventromedial group.
      The dorsolateral group consisted of neurons immunoreactive for calcitonin gene
      related peptide, whereas the ventrolateral-caudal group was negative for
      calcitonin gene-related peptide. The latter group was retrogradely labeled after
      dextran amine injection to the visceral ramus of the vagus nerve, suggesting that
      it is a general visceral efferent column, made up of parasympathetic
      preganglionic neurons, whereas the dorsolateral rostral group is a special
      visceral efferent column. In the general visceral efferent column, a dense
      concentration of nerve fibers immunoreactive for serotonin, tyrosine hydroxylase,
      cholecystokinin-8, and substance P, and a small number of fibers immunoreactive
      for neuropeptide Y was observed. Perikarya in contact with varicose terminals
      immunoreactive for these substances were frequently seen. In contrast, in the
      special visceral efferent column, only a moderate concentration of neuropeptide Y
      immunoreactive nerve fibers and a sparse distribution of fibers immunoreactive
      for tyrosine hydroxylase were observed. Perikarya in contact with varicose
      terminals immunoreactive for these substances were rare. These results suggest
      that the vagal parasympathetic preganglionic neurons might receive multiple
      inputs of monoaminergic and peptidergic fibers involved in the regulation of the
      visceral organs. On the other hand, monoaminergic and peptidergic afferent fibers
      might be of much less significance in the activity of the special visceral
      efferent component of the vagus nerve.

PMID- 11992522
TI  - Neuroanatomical studies of period gene expression in the hawkmoth, Manduca sexta.
AB  - In the nervous system of the hawkmoth, Manduca sexta, cells expressing the period
      (per)gene were mapped by in situ hybridization and immunocytochemical methods.
      Digoxigenin-labeled riboprobes were transcribed from a 1-kb M. sexta per cDNA.
      Monoclonal anti-PER antibodies were raised to peptide antigens translated from
      both M. sexta and Drosophila melanogaster per cDNAs. These reagents revealed a
      widespread distribution of per gene products in M. sexta eyes, optic lobes,
      brains, and retrocerebral complexes. Labeling for per mRNA was prominent in
      photoreceptors and in glial cells throughout the brain, and in a cluster of 100
      200 neurons adjacent to the accessory medulla of the optic lobes. Daily rhythms
      of per mRNA levels were detected only in glial cells. PER-like immunoreactivity
      was observed in nuclei of most neurons and glial cells and in many photoreceptor
      nuclei. Four neurosecretory cells in the pars lateralis of each brain hemisphere
      exhibited both nuclear and cytoplasmic staining with anti-PER antibodies. These
      cells were positively identified as Ia(1) neurosecretory cells that express
      corazonin immunoreactivity. Anti-corazonin labeled their projections in the brain
      and their neurohemal endings in the corpora cardiaca and corpora allata. Four
      pairs of PER-expressing neurosecretory cells previously described in the
      silkmoth, Anthereae pernyi, are likely to be homologous to these PER/corazonin
      expressing Ia(1) cells of M. sexta. Other findings, such as widespread nuclear
      localization of M. sexta PER and rhythmic expression in glial cells, are
      reminiscent of the period gene of D. melanogaster, suggesting that some functions
      of per may be conserved in this lepidopteran species.

PMID- 11992523
TI  - Apoptosis of spinal interneurons induced by sciatic nerve axotomy in the neonatal
      rat is counteracted by nerve growth factor and ciliary neurotrophic factor.
AB  - We have previously shown that not only motoneurons and dorsal root ganglion cells
      but also small neurons, presumably interneurons in the spinal cord, may undergo
      apoptotic cell death as a result of neonatal peripheral nerve transection in the
      rat. With the aid of electron microscopy, we have here demonstrated that
      apoptosis in the spinal cord is confined to neurons and does not involve glial
      cells at the survival time studied (24 hours). To define the relative importance
      of the loss of a potential target (motoneuron) and a potential afferent input
      (dorsal root ganglion cell) for the induction of apoptosis in interneurons in
      this situation, we have compared the distributions and time courses for TUNEL
      labeling, which detects apoptotic cell nuclei, in the L5 segment of the spinal
      cord and the L5 dorsal root ganglion after sciatic nerve transection in the
      neonatal (P2) rat. In additional experiments, we studied the effects on TUNEL
      labeling of interneurons after treatment of the cut sciatic nerve with either
      ciliary neurotrophic factor (CNTF) to rescue motoneurons or nerve growth factor
      (NGF) to rescue dorsal root ganglion cells. The time courses of the TUNEL
      labeling in motoneurons and interneurons induced by the lesion show great
      similarities (peak at 8-48 hours postoperatively), whereas the labeling in dorsal
      root ganglion cells occurs later (24-72 hours). Both CNTF and NGF decrease the
      number of TUNEL-labeled interneurons, but there is a regional difference, in that
      CNTF preferentially saves interneurons in deep dorsal and ventral parts of the
      spinal cord, whereas the rescuing effects of NGF are seen mainly in the
      superficial dorsal horn. The results are interpreted as signs of a trophic
      dependence on both the target and the afferent input for the survival of
      interneurons neonatally.

PMID- 11992524
TI  - Perirhinal and parahippocampal cortices of the macaque monkey: projections to the
      neocortex.
AB  - We investigated the topographic and laminar organization of the efferent cortical
      projections of the perirhinal and parahippocampal cortices. Area 36 of the
      perirhinal cortex projects preferentially to areas TE and TEO, whereas area TF of
      the parahippocampal cortex projects preferentially to the posterior parietal
      cortex and area V4. Area TF projects to many regions of the frontal lobe, whereas
      area 36 projects mainly to the orbital surface. The insular and cingulate
      cortices receive projections from areas 36 and TF, whereas only area TF projects
      to the retrosplenial cortex. Projections to the superior temporal gyrus,
      including the dorsal bank of the superior temporal sulcus, arise predominantly
      from area TF. Area 36 projects only to rostral levels of the superior temporal
      gyrus. Area TF has, in general, reciprocal connections with the neocortex,
      whereas area 36 has more asymmetric connections. Area 36, for example, projects
      to more restricted regions of the frontal cortex and superior temporal sulcus
      than it receives inputs from. In contrast, it projects to larger portions of
      areas TE and TEO than it receives inputs from. The efferent projections of areas
      36 and TF are primarily directed to the superficial layers of the neocortex, a
      laminar organization consistent with connections of the feedback type.
      Projections to unimodal visual areas terminate in large expanses of the cortex,
      but predominantly in layer I. Projections to other sensory and polymodal areas,
      in contrast, terminate in a columnar manner predominantly in layers II and III.
      In all areas receiving heavy projections, the projections extend throughout most
      cortical layers, largely avoiding layer IV. We discuss these findings in relation
      to current theories of memory consolidation.

PMID- 11992525
TI  - A kinetic model for enzyme interfacial activity and stability: pa-hydroxynitrile
      lyase at the diisopropyl ether/water interface.
AB  - A kinetic framework is developed to describe enzyme activity and stability in two
      phase liquid-liquid systems. In particular, the model is applied to the enzymatic
      production of benzaldehyde from mandelonitrile by Prunus amygdalus hydroxynitrile
      lyase (pa-Hnl) adsorbed at the diisopropyl ether (DIPE)/aqueous buffer interface
      (pH = 5.5). We quantitatively describe our previously obtained experimental
      kinetic results (Hickel et al., 1999; 2001), and we successfully account for the
      aqueous-phase enzyme concentration dependence of product formation rates and the
      observed reaction rates at early times. Multilayer growth explains the early time
      reversibility of enzyme adsorption at the DIPE/buffer interface observed by both
      enzyme-activity and dynamic-interfacial-tension washout experiments that replace
      the aqueous enzyme solution with a buffer solution. The postulated explanation
      for the unusual stability of pa-Hnl adsorbed at the DIPE/buffer interface is
      attributed to a two-layer adsorption mechanism. In the first layer, slow
      conformational change from the native state leads to irreversible attachment and
      partial loss of catalytic activity. In the second layer, pa-Hnl is reversibly
      adsorbed without loss in catalytic activity. The measured catalytic activity is
      the combined effect of the deactivation kinetics of the first layer and of the
      adsorption kinetics of each layer. For the specific case of pa-Hnl adsorbed at
      the DIPE/buffer interface, this combined effect is nearly constant for several
      hours resulting in no apparent loss of catalytic activity. Our proposed kinetic
      model can be extended to other interfacially active enzymes and other organic
      solvents. Finally, we indicate how interfacial-tension lag times provide a
      powerful tool for rational solvent selection and enzyme engineering.

PMID- 11992526
TI  - A kinetic model for surfactant inhibition of pentachlorophenol biodegradation.
AB  - A kinetic model is used to describe the effect of the nonionic surfactant
      Tergitol NP-10 (TNP10) on pentachlorophenol (PCP) biodegradation by Sphingomonas
      chlorophenolica sp. strain RA2. Different initial biomass to initial substrate
      ratios ranging from 13 to 418 were tested with 23 TNP10 concentrations ranging
      from 0 to 1500 mg/L. Tests were also conducted at 10 degrees C and 20 degrees C.
      No PCP biodegradation inhibition was observed at concentrations below the
      critical micelle concentration (CMC) of 50 mg/L. TNP10 concentrations above 100
      to 200 mg/L were increasingly inhibitory to PCP biodegradation rates. This
      inhibition was best described by the Monod kinetic equation wherein the effect of
      TNP10 inhibition is reflected in the half-saturation constant (Ks). The value of
      the Ks increased from between 1.5 and 13.5 mg/L with no surfactant present to 44
      to 131 mg/L at 1000 mg/L TNP10. Using a standard competitive inhibition approach,
      the inhibition constant for TNP10 was approximately 100 mg/L at both 10 degrees C
      and 20 degrees C.

PMID- 11992527
TI  - Effects of oxygen on engineered cardiac muscle.
AB  - Concentration gradients associated with the in vitro cultivation of engineered
      tissues that are vascularized in vivo result in the formation of only a thin
      peripheral tissue-like region (e.g., approximately 100 microm for engineered
      cardiac muscle) around a relatively cell-free interior. We previously
      demonstrated that diffusional gradients within engineered cardiac constructs can
      be minimized by direct perfusion of culture medium through the construct. In the
      present study, we measured the effects of medium perfusion rate and local oxygen
      concentration (p(O2)) on the in vitro reconstruction of engineered cardiac
      muscle. Neonatal rat cardiomyocytes were seeded onto biodegradable polymer
      scaffolds (fibrous discs, 1.1 cm diameter x 2 mm thick, made of polyglycolic
      acid, 24 x 10(6) cells per scaffold). The resulting cell-polymer constructs were
      cultured for a total of 12 days in serially connected cartridges (n = 1-8), each
      containing one construct directly perfused with culture medium at a flow rate of
      0.2-3.0 mL/min. In all groups, oxygen concentration decreased due to cell
      respiration, and depended on construct position in the series and medium flow
      rate. Higher perfusion rates and higher p(O2) correlated with more aerobic cell
      metabolism, and higher DNA and protein contents. Constructs cultured at p(O2) of
      160 mm Hg had 50% higher DNA and protein contents, markedly higher expression of
      sarcomeric alpha-actin, better organized sarcomeres and cell junctions, and 4.5
      fold higher rate of cell respiration as compared to constructs cultured at p(O2)
      of 60 mm Hg. Contraction rates of the corresponding cardiac cell monolayers were
      40% higher at p(O2) of 160 than 60 mm Hg. The control of oxygen concentration in
      cell microenvironment can thus improve the structure and function of engineered
      cardiac muscle. Experiments of this kind can form a basis for controlled studies
      of the effects of oxygen on the in vitro development of engineered tissues.

PMID- 11992528
TI  - Quantitative analysis of experiments on bacterial chemotaxis to naphthalene.
AB  - A mathematical model was developed to quantify chemotaxis to naphthalene by
      Pseudomonas putida G7 (PpG7) and its influence on naphthalene degradation. The
      model was first used to estimate the three transport parameters (coefficients for
      naphthalene diffusion, random motility, and chemotactic sensitivity) by fitting
      it to experimental data on naphthalene removal from a discrete source in an
      aqueous system. The best-fit value of naphthalene diffusivity was close to the
      value estimated from molecular properties with the Wilke-Chang equation.
      Simulations applied to a non-chemotactic mutant strain only fit the experimental
      data well if random motility was negligible, suggesting that motility may be lost
      rapidly in the absence of substrate or that gravity may influence net random
      motion in a vertically oriented experimental system. For the chemotactic wild
      type strain, random motility and gravity were predicted to have a negligible
      impact on naphthalene removal relative to the impact of chemotaxis. Based on
      simulations using the best-fit value of the chemotactic sensitivity coefficient,
      initial cell concentrations for a non-chemotactic strain would have to be several
      orders of magnitude higher than for a chemotactic strain to achieve similar rates
      of naphthalene removal under the experimental conditions we evaluated. The model
      was also applied to an experimental system representing an adaptation of the
      conventional capillary assay to evaluate chemotaxis in porous media. Our analysis
      suggests that it may be possible to quantify chemotaxis in porous media systems
      by simply adjusting the model's transport parameters to account for tortuosity,
      as has been suggested by others.

PMID- 11992529
TI  - Strategies for manipulating the relative concentration of recombinant rotavirus
      structural proteins during simultaneous production by insect cells.
AB  - Adequate production strategies of virus-like particles are among the challenges
      that must be addressed before such complex multimeric structures find practical
      applications as vaccines. Attainment of the correct stoichiometric relation
      between proteins that constitute virus-like particles should result in an
      increased productivity by maximizing the concentration of assembled proteins and
      preventing the accumulation of waste monomers. In this work, strategies for
      manipulating the relative concentration between two of the structural proteins
      that constitute rotavirus-like particles (VP2 and VP6) were explored using the
      insect cell baculovirus expression vector system. It was shown that multiplicity
      of infection is a useful tool for manipulating protein production rates and
      maximum concentrations in cultures expressing one or two recombinant proteins.
      Thus, multiplicity of infection can be employed for improving production of
      rotavirus-like particles. VP2 and VP6 production rates obtained during individual
      infections remained unchanged when both were simultaneously produced, indicating
      that such rates can be utilized for estimating protein concentrations during
      coexpression. Manipulation of the time of infection between the two recombinant
      baculoviruses, proposed here for the first time, also proved to be effective for
      controlling the relative protein concentrations. The use of such sequential
      infections constituted an effective production alternative that does not require
      high amounts of virus stocks and is easy to implement. In addition to VP2 and
      VP6, kinetic parameters for the individual production of the other two proteins
      (VP4 and VP7) that constitute rotavirus-like particles were also obtained.

PMID- 11992530
TI  - Control of starvation-induced apoptosis in Chinese hamster ovary cell cultures.
AB  - The application of the unscented Kalman filter to control starvation-induced
      programmed cell death-apoptosis-in Chinese hamster ovary cells was investigated.
      Neural network-based sensitivity analysis identified glutamine and asparagine as
      two major amino acids that play a key role in the suppression of apoptosis.
      Dynamic equations that accounted for the dependence of apoptotic cells on the
      concentrations of viable cells, glutamine, and asparagine were derived. These
      state equations were highly nonlinear and included nine state variables. An
      oxygen mass balance was written in the liquid phase. It served as the output
      equation for the unscented Kalman filter. Using the oxygen uptake rate as the
      observer, it was possible to estimate the states. A model predictive controller
      was then implemented once the apoptotic cells in the bioreactor approached a
      concentration of 1.5 x 10(4) cells/mL, taking into account the operating range of
      the flow cytometer and measurement error. The manipulated variables were the flow
      rates of glucose, glutamine, and asparagine. Simulation results showed that the
      controller was able to keep the apoptotic cells at a concentration of 1.5 x 10(4)
      cells/mL.

PMID- 11992531
TI  - An assessment of seed quality and its influence on productivity estimation in an
      industrial antibiotic fermentation.
AB  - This study investigates the benefits of including seed quality information into
      data-based models for final productivity estimation in an industrial antibiotic
      fermentation process. Multiway principal component analysis is applied to assess
      the seed quality using routinely gathered plant data. Multiway partial least
      squares regression is then used to estimate the final productivity using data
      from the main fermentation only. The issue of selecting appropriate process
      variables as inputs is investigated. Subsequently, seed characteristics are
      included into the estimation models to assess the benefits of including
      information from this stage for productivity estimation. It is shown that it is
      possible to extract seed fermentation features related to the final productivity
      both at pilot and production scales. It is postulated that significant
      influential variations are mirrored in monitored variables during the main
      fermentation, and therefore seed quality is implicitly accounted for.

PMID- 11992532
TI  - Hybrid neural network modeling of a full-scale industrial wastewater treatment
      process.
AB  - In recent years, hybrid neural network approaches, which combine mechanistic and
      neural network models, have received considerable attention. These approaches are
      potentially very efficient for obtaining more accurate predictions of process
      dynamics by combining mechanistic and neural network models in such a way that
      the neural network model properly accounts for unknown and nonlinear parts of the
      mechanistic model. In this work, a full-scale coke-plant wastewater treatment
      process was chosen as a model system. Initially, a process data analysis was
      performed on the actual operational data by using principal component analysis.
      Next, a simplified mechanistic model and a neural network model were developed
      based on the specific process knowledge and the operational data of the coke
      plant wastewater treatment process, respectively. Finally, the neural network was
      incorporated into the mechanistic model in both parallel and serial
      configurations. Simulation results showed that the parallel hybrid modeling
      approach achieved much more accurate predictions with good extrapolation
      properties as compared with the other modeling approaches even in the case of
      process upset caused by, for example, shock loading of toxic compounds. These
      results indicate that the parallel hybrid neural modeling approach is a useful
      tool for accurate and cost-effective modeling of biochemical processes, in the
      absence of other reasonably accurate process models.

PMID- 11992533
TI  - Purification, characterization, thermal, and high-pressure inactivation of pectin
      methylesterase from bananas (cv Cavendish).
AB  - Pectin methylesterase (PME) was extracted from bananas (cv Cavendish) and
      purified by affinity chromatography on a CNBr-Sepharose-PME inhibitor (PMEI)
      column. A single protein and PME activity peak was obtained. For banana PME, a
      biochemical characterization in terms of molar mass (MM), pI, and kinetic
      parameters was performed. In a second step, the thermal and high-pressure
      stability of the enzyme was studied. Isothermal inactivation of purified banana
      PME could be described by a first-order kinetic model in a temperature range of
      65 degrees to 72.5 degrees C, whereas its isobaric-isothermal inactivation
      followed a fractional-conversion model. Banana PME was found to be more thermally
      stable compared with PMEs extracted from orange, tomato, and apple.

PMID- 11992534
TI  - Production of wild-type and peptide fusion cutinases by recombinant Saccharomyces
      cerevisiae MM01 strains.
AB  - This study focused on the growth of Saccha-romyces cerevisiae MM01 recombinant
      strains and the respective production of three extracellular heterologous
      cutinases: a wild-type cutinase and two cutinases in which the primary structure
      was fused with the peptides (WP)(2) and (WP)(4), respectively. Different
      cultivation and strategies were tested in a 2-L shake flask and a 5-L bioreactor,
      and the respective cell growth and cutinase production were analyzed and compared
      for the three yeast strains. The highest cutinase productions and productivities
      were obtained in the fed-batch culture, where wild-type cutinase was secreted up
      to a level of cutinase activity per dry cell weight (specific cell activity) of
      4.1 Umg(-1) with activity per protein broth (specific activity) of 266 Umg(-1),
      whereas cutinase-(WP)(2) was secreted with a specific cell activity of 2.1 Umg(
      1) with a specific activity of 200 Umg(-1), and cutinase-(WP)(4) with a specific
      cell activity of 0.7 Umg(-1) with a specific activity of 15 Umg(-1). The results
      indicate that the fusion of hydrophobic peptides to cutinase that changes the
      physical properties of the fused protein limits cutinase secretion and
      subsequently leads to a lower plasmid stability and lower yeast cell growth.
      These effects were observed under different cultivation conditions (shake flask
      and bioreactor) and cultivation strategies (batch culture versus fed-batch
      culture).

PMID- 11992535
TI  - Simultaneous production of polyhydroxyalkanoates and rhamnolipids by Pseudomonas
      aeruginosa.
AB  - The feasibility of the simultaneous production of polyhydroxyalkanoates (PHAs)
      and rhamnolipids, as a novel approach to reduce their production costs, was
      demonstrated by the cultivation of Pseudomonas aeruginosa IFO3924. Fairly large
      amounts of PHAs and rhamnolipids were obtained from the bacterial cells and the
      culture supernatant, respectively. Decanoate was a more suitable carbon source
      than ethanol and glucose for the simultaneous production, although glucose was
      suitable for cell growth without an induction period under pH control. The kind
      of carbon source affected PHA monomer composition markedly and PHA molecular
      weight slightly. Monorhamnolipids and dirhamnolipids were included in the
      rhamnolipids extracted from the culture supernatant using decanoate, glucose, or
      ethanol as the carbon source. Both PHAs and rhamnolipids were synthesized after
      the growth phase. PHA content in the cell reached a maximum when the carbon
      source was exhausted. After exhaustion of the carbon source, PHA content
      decreased rapidly, but rhamnolipid synthesis, which followed PHA synthesis,
      continued. This resulted in a time lag for the attainment of maximum levels of
      PHAs and rhamnolipids. The reusability of the cells used in rhamnolipid
      production was evaluated in the repeated batch culture of P. aeruginosa IFO3924
      for the simultaneous production of PHAs and rhamnolipids. High concentrations of
      rhamnolipids in the culture supernatant were attained at the end of both the
      first and second batch cultures. High PHA content was achieved in the resting
      cells that were finally harvested after the second batch. Simultaneous production
      of PHAs and rhamnolipids will enhance the availability of valuable biocatalysts
      of bacterial cells, and dispel the common belief that the production cost of PHAs
      accumulated intracellularly is almost impossible to become lower than that of
      cells themselves.

PMID- 11992536
TI  - Kinetic analysis of high-concentration isopropanol biodegradation by a solvent
      tolerant mixed microbial culture.
AB  - The ability of a previously enriched microbial population to utilize isopropanol
      (IPA) as the sole carbon source within a minimal salts medium is studied. The
      advantage of prior enrichment procedures for the improvement of IPA
      biodegradation performance is demonstrated for an IPA concentration of up to 24 g
      L(-1). Results showing the interrelationship between temperature and substrate
      utilization and inhibition levels at temperatures of between 2 degrees C and 45
      degrees C are examined. Models of inhibition based on enzyme kinetics are
      assessed via nonlinear analysis, in order to accurately represent the growth
      kinetics of this solvent-tolerant mixed culture. The model that best describes
      the data is the Levenspiel substrate inhibition model, which can predict the
      maximum substrate level above which growth is completely limited. This is the
      first report of IPA treatment of up to 24 g L(-1) by an aerobic solvent-tolerant
      population.

PMID- 11992537
TI  - Gene-specific oxidative DNA damage in Helicobacter pylori-infected human gastric
      mucosa.
AB  - To study the status of oxidative DNA damage in Helicobacter pylori infection in
      more detail, we examined oxidative DNA damage to individual genes by determining
      the loss of PCR product of a targeted gene before and after gastric mucosal DNA
      was treated with 8-hydroxyguanine glycosylase, which cleaves DNA at the 8
      hydroxyguanine residues. The results showed that, of the 5 genes tested, p53,
      insulin-like growth factor II receptor and transforming growth factor-beta
      receptor type II showed significant oxidative DNA damage in H. pylori-positive
      tissues and that the BAX and beta-ACTIN genes were relatively undamaged. These
      results suggest that in H. pylori infection, oxidative DNA damage does not occur
      homogeneously throughout the genomic DNA but, rather, in a gene-specific manner.
      We conclude that the progressive accumulation of preferential oxidative DNA
      damage in certain genes, such as p53, likely contributes to gastric
      carcinogenesis.

PMID- 11992538
TI  - Chemotherapeutic agents sensitize osteogenic sarcoma cells, but not normal human
      bone cells, to Apo2L/TRAIL-induced apoptosis.
AB  - Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines
      that induces death of cancer cells but not normal cells. Its potent apoptotic
      activity is mediated through its cell surface death domain-containing receptors,
      DR4 and DR5. Apo2L/TRAIL interacts also with 3 "decoy" receptors that do not
      induce apoptosis, DcR1, DcR2, which lack functional death domains, and
      osteoprotegerin (OPG). The aim of our study was to investigate the cytotoxic
      activity of Apo2L/TRAIL on established osteogenic sarcoma cell lines (BTK-143,
      HOS, MG-63, SJSA-1, G-292 and SAOS2) and in primary cultures of normal human bone
      (NHB) cells. When used alone, Apo2L/TRAIL at 100 ng/ml for 24 hr induced greater
      than 80% cell death in only 1 (BTK-143) of the 6 osteogenic sarcoma cell lines.
      In contrast, Apo2L/TRAIL-resistant cells were susceptible to Apo2L/TRAIL-mediated
      apoptosis in the presence of the anticancer drugs, Doxorubicin (DOX), Cisplatin
      (CDDP) and Etoposide (ETP) but not Methotrexate (MTX) or Cyclophosphamide (CPM).
      Importantly, neither Apo2L/TRAIL alone nor in combination with any of these drugs
      affected primary normal human bone cells under equivalent conditions. Apo2L/TRAIL
      induced apoptosis, and its augmentation by chemotherapy in the resistant cell
      lines was mediated through caspase-8 and caspase-3 activation. Furthermore,
      Apo2L/TRAIL-induced apoptosis and its augmentation by chemotherapy was
      effectively inhibited by caspase-8 zIETD-fmk and caspase-3 zDEVD-fmk protease
      inhibitors and by the pan-caspase inhibitor zVAD-fmk. The pattern of basal
      Apo2L/TRAIL receptor mRNA expression, or expression of the intracellular caspase
      inhibitor FLICE-inhibitory protein, FLIP, could not be readily correlated with
      resistance or sensitivity to Apo2L/TRAIL-induced apoptosis. However, the
      augmentation of Apo2L/TRAIL effects by chemotherapy was associated with drug
      induced up-regulation of death receptors DR4 and DR5 mRNA and protein. No obvious
      correlation was seen between the expression of OPG mRNA or protein and
      susceptibility of cells to Apo2L/TRAIL-induced apoptosis. Stable over-expression
      of a dominant negative form of the Fas-associated death domain protein (FADD) in
      the Apo2L/TRAIL-sensitive BTK-143 cells completely inhibited Apo2L/TRAIL-induced
      cell death. Our results indicate that chemotherapy and Apo2L/TRAIL act
      synergistically to kill cancer cells but not normal bone-derived osteoblast-like
      cells, which has implications for future therapy of osteosarcoma.

PMID- 11992539
TI  - Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal
      and epidermal growth factor-induced cell proliferation and metastasis-associated
      properties in human epidermoid carcinoma A431 cells.
AB  - The purpose of this study was to investigate the effects of a potent LHRH
      agonist, [D-Trp(6)]LHRH on the basal and EGF-induced cell proliferation and the
      metastasis-associated properties in A431 human epidermoid carcinoma. [D
      Trp(6)]LHRH time-dependently inhibited the basal and EGF-stimulated growth of
      A431 cancer cells. It is assumed that phosphorylation/dephosphorylation of
      cellular proteins is highly related to cell growth. This study demonstrates that
      [D-Trp(6)]LHRH decreased the basal and EGF-induced total cellular kinase
      activity, particularly the tyrosine phosphorylation of several cellular proteins
      including the EGFR. In contrast, [D-Trp(6)]LHRH did not cause detectable changes
      in basal and EGF-stimulated serine/threonine phosphorylation of A431 cellular
      proteins. The inhibitory effect of [D-Trp(6)]LHRH on A431 cell proliferation was
      associated with apoptosis as evidenced by the cell morphology and DNA integrity
      (ladder pattern), the expression of interleukin 1beta-converting enzyme (ICE) and
      activation of caspase. Furthermore, EGF could rescue the remaining attached A431
      cells following [D-Trp(6)]LHRH treatment for 48 hr, which suggests that limited
      exposure to [D-Trp(6)]LHRH did not channel all cells to irreversible apoptotic
      process. We also determined the effects of [D-Trp(6)]LHRH on metastasis
      associated properties in A431 cells. [D-Trp(6)]LHRH reduced both basal and EGF
      stimulated secretion of MMP-9 and MMP-2. In addition, [D-Trp(6)]LHRH suppressed
      the basal and EGF-induced invasive activity of A431 cells based on an in vitro
      invasion assay. In conclusion, this study indicates that [D-Trp(6)]LHRH may act
      partly through activating tyrosine phosphatase activity to inhibit cell
      proliferation and the metastasis-associated properties of A431 cancer cells. Our
      work suggests that [D-Trp(6)]LHRH may be therapeutically useful in limiting the
      tumor growth and metastasis of some neoplasms.

PMID- 11992540
TI  - Melphalan availability in hypoxia-inducible factor-1alpha+/+ and factor-1alpha-/-
      tumors is independent of tumor vessel density and correlates with melphalan
      erythrocyte transport.
AB  - Many tumors are impervious to anticancer agents. Resistance due to lack of
      cytotoxic penetration into the tumor is often overlooked but can play a
      significant role in undermining therapy. Insufficient and irregular
      vascularization of tumors is a possible barrier to drug delivery, but there are
      others, e.g., impaired vessel permeability and poor interstitial transport. We
      evaluated the importance of tumor vessel density in the availability of melphalan
      to tumors. A nude mouse tumor model with different vascularization due to a
      single-gene deletion of hypoxia-inducible factor 1alpha (HIF-1alpha(+/+) and HIF
      1alpha(-/-) embryonic stem cell-derived tumors) was used. The availability of
      melphalan to HIF-1alpha(+/+) (n = 20) and HIF-1alpha(-/-) (n = 23) tumors was not
      significantly different (p = 0.12). Furthermore, in the various subgroup analyses
      accentuating the difference in vessel density, no significant correlation between
      vessel density and melphalan availability was found. In the second part of the
      study, melphalan, was demonstrated to be transported in blood in mice with a
      distribution of 24% in erythrocytes vs. 76% in plasma. A strong correlation (r =
      0.93, p < 0.000001) between melphalan concentrations in plasma and erythrocytes
      was found, indicating an equilibrium between these 2 compartments. Plasma and
      erythrocyte concentrations of melphalan are correlated with the tumor
      availability of melphalan (r = 0.66 and 0.64, respectively, both p < 0.001).
      These data suggest that tumor vessel density is not an important predictor of the
      tumor availability of small cytotoxic drugs such as melphalan and indicate the
      importance of erythrocytes in the transport of melphalan.

PMID- 11992541
TI  - Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by
      stimulating production of matrix metalloproteinases by fibroblasts.
AB  - EMMPRIN, which is identical to human basigin (CD147), interacts with fibroblasts
      and stimulates expression of MMPs, which play an important role in tumor
      invasiveness and metastasis. In the present study, we demonstrated that coculture
      of basigin-expressing human MM cells with dermal fibroblasts resulted in the
      induction of MMP-1, MMP-2, MMP-3 and MT1-MMP production by fibroblasts and of
      melanoma cell invasion through a reconstituted basement membrane. Antibody to
      basigin inhibited both the production of MMPs by fibroblasts and the invasiveness
      of melanoma cells. Expression of basigin and MMPs in MM and surrounding
      fibroblasts was examined immunohistochemically in 28 specimens from 18 MM
      patients without metastasis and 10 with metastasis, to investigate whether
      basigin plays a role in metastasis of MM in vivo. Basigin was expressed in
      melanoma cells but not in fibroblasts. MM with metastasis had significantly
      higher basigin expression compared to MM without metastasis. There were
      significant differences between MMs with and without metastasis in the expression
      of MMPs in both melanoma cells and fibroblasts. Expression of MMPs in fibroblasts
      was positively correlated with expression levels of basigin. These
      immunohistochemic findings indicate that MMPs might be expressed in fibroblasts
      as well as melanoma cells concomitantly with basigin, which was expressed in
      melanoma cells more frequently in MM with metastasis. Basigin is highly expressed
      in melanoma cells and may play an important role in their invasiveness and
      metastasis by stimulating surrounding fibroblasts to express MMPs.

PMID- 11992542
TI  - Integrin expression in colon cancer cells is regulated by the cytoplasmic domain
      of the beta6 integrin subunit.
AB  - We have previously reported that the alphavbeta6 integrin upregulates its own
      expression in a protein kinase C-dependent manner with increasing cell density.
      The wild-type beta6 integrin subunit has also been shown to promote tumour growth
      in vivo and its growth-enhancing effect is regulated by both a MAP kinase binding
      motif on beta6 and the 11 amino acid C-terminal cytoplasmic extension unique to
      the beta6 subunit. Herein, we show that the 11 amino acid cytoplasmic extension
      is essential for the cell density-dependent increase in beta6 expression and that
      the 11 amino acid tail exerts a dominant negative effect on cell density- and PKC
      mediated beta5 expression in alphavbeta6-expressing colon cancer cells. Cells
      that express beta6 lacking the 11 amino acid tail respond to PKC simulation with
      increased expression of only the beta5 subunit as seen for cells that lack
      constitutive alphavbeta6 expression. In contrast, loss of the ERK binding site on
      beta6 markedly impairs cell density- and PKC-dependent expression of either beta6
      or beta5 in the presence or absence of the 11 amino acid tail, respectively. Our
      findings suggest that in alphavbeta6-expressing cells, a hierarchy of kinase
      signalling cascades exists and that the beta6-ERK2 interaction dominates over PKC
      mediated signalling pathways responsible for integrin upregulation with cell
      confluence. Given the dominance of the beta6-ERK2 interaction over PKC-mediated
      expression of both beta5 and beta6 integrin subunits, targeting the beta6-ERK2
      interaction may prove useful as an anticancer strategy in colon cancer.

PMID- 11992543
TI  - Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K
      and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF
      expression in human head and neck squamous cell carcinoma lines.
AB  - We previously reported that expression of angiogenesis factors interleukin-8 (IL
      8) and vascular endothelial growth factor (VEGF) is promoted by coactivation of
      transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1
      (AP-1) by interleukin-1alpha in human head and neck squamous cell carcinomas
      (HNSCC). However, expression of IL-1 receptor antagonist incompletely blocked
      reporter gene activity and cytokine expression, suggesting that other upstream
      signals may contribute to activation. Overexpression and autocrine activation of
      epidermal growth factor receptor (EGFR) is detected in 90% of HNSCC, and EGFR
      inhibitors have been reported to inhibit IL-8 and VEGF expression, but the
      intermediary signal pathways and transcription factors by which EGFR modulates
      proangiogenic factors is unknown. EGFR can activate the phosphotidylinositol-3
      kinase (PI3K) and mitogen-activated/extracellular signal-regulated kinase (MEK)
      pathways, which can potentially modulate activation of NF-kappaB and AP-1,
      respectively. In our study, we examined the effect of EGF and antagonists of
      EGFR, PI3K and MEK on NF-kappaB and AP-1 activation and IL-8 and VEGF expression
      in HNSCC cell lines UM-SCC-9 and 11B in which EGFR is overexpressed and
      activated. Recombinant EGF induced EGFR phosphorylation, activation of NF-kappaB
      and AP-1 reporter genes and IL-8 and VEGF expression, indicating that EGFR can
      mediate coactivation of both transcription factors and cytokine genes in HNSCC.
      EGFR antagonist PD153035 and anti-EGFR antibody C225 completely inhibited EGF
      induced reporter activity and cytokine expression, but only partially inhibited
      constitutive activity. MEK inhibitor U0126 preferentially blocked AP-1 activity
      and expression of both IL-8 and VEGF, while PI3K inhibitor LY-294002 or a
      dominant negative inhibitor-kappaB preferentially blocked NF-kappaB activation
      and expression of IL-8 but not VEGF. EGFR, PI3K and MEK antagonists inhibited
      growth of HNSCC. We conclude that antagonists of EGFR, PI3K and MEK signal
      pathways have inhibitory activity against EGFR-induced NF-kappaB and AP-1
      activation, IL-8 and VEGF expression and growth by HNSCC. Published 2002 Wiley
      Liss, Inc.

PMID- 11992544
TI  - Molecular evidence of a common clonal origin and subsequent divergent clonal
      evolution in vulval intraepithelial neoplasia, vulval squamous cell carcinoma and
      lymph node metastases.
AB  - VIN is thought to be the precursor of some VSCCs because it is monoclonal,
      frequently occurs contiguously with VSCC and shares similar risk factors with a
      subgroup of VSCC. There has been no conclusive molecular evidence supporting this
      assumption. We performed X-chromosome inactivation analysis on 9 cases of lone
      VIN, 10 cases of VSCC and associated contiguous VIN and 11 cases of VSCC and
      associated noncontiguous VIN. Eight of the 9 cases of lone VIN appeared to be
      monoclonal. All 7 informative and monoclonal cases of VIN with contiguous VSCC
      and 6/9 informative cases of VIN with noncontiguous VSCC showed patterns of X
      chromosome inactivation consistent with a common monoclonal origin for both VIN
      and VSCC. Two of the 9 cases of VIN with noncontiguous VSCC showed X-chromosome
      inactivation patterns consistent with a separate clonal origin. We performed LOH
      analysis at 6 chromosomal loci on these samples and 7 cases with lymph node
      metastases. Identical losses occurred 7 times in VIN and contiguous VSCC (random
      probability 1.2 x 10(-9)), twice in VIN and noncontiguous VSCC (random
      probability 1.5 x 10(-3)) and 3 times in VSCC and associated metastases (random
      probability 1.8 x 10(-5)). Some losses occurring in VSCC did not appear in the
      contiguous VIN or associated metastases and vice versa. These data provide
      molecular evidence that VIN is the precursor of VIN-associated VSCC, that
      multifocal disease may arise via either different clones or a single clone and
      that continued divergent clonal evolution may occur in vulval neoplasia.

PMID- 11992545
TI  - Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse
      strains.
AB  - Lung tumor susceptibility in inbred mouse strains is caused by the susceptibility
      allele at the pulmonary adenoma susceptibility 1 (Pas1(s)) locus. However, after
      urethane treatment, most strains carrying the Pas1(s) allele show an intermediate
      (1-4 tumors/mouse) instead of a highly susceptible (15-30 tumors/mouse) lung
      tumor phenotype. To test the hypothesis that strains displaying the intermediate
      lung tumor phenotype carry dominant or codominant resistance alleles at pulmonary
      adenoma resistance (Par) loci, we crossed mice of intermediate susceptibility or
      resistance to lung tumorigenesis with the highly susceptible A/J strain. Eleven
      F(1) hybrids were treated with urethane to induce lung tumorigenesis. The A/J
      strain developed 35.3 tumors/mouse, while its F(1) hybrid with C57BL/6J mice
      (null allele at Par loci) developed 22.8 tumors/mouse due to the Pas1 allele
      dosage effect. F(1) hybrids of strains 129/SvJ, CBA/J, ST/J and LP/J (Pas1(s))
      and of SPW, DBA/2J and C57L/J (Pas1(r)) mice showed significant reduction in lung
      tumor multiplicity (i.e., 0.3-12.8 tumors/mouse) compared to A/J and (A/J x
      C57BL/6J)F(1) mice. These results indicate that resistance alleles at Par loci
      are common in inbred mouse strains and account for the lung tumorigenesis
      intermediate phenotype of strains carrying the Pas1(s) allele.

PMID- 11992546
TI  - Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell
      sarcoma of tendons and aponeuroses.
AB  - Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly
      associated with tendons and aponeuroses. The cytogenetic hallmark is the
      translocation t(12;22)(q13;q12) resulting in a chimeric EWS/ATF1 gene in which
      the 3'-terminal part of EWS at 22q is replaced by the 3'-terminal part of ATF1 at
      12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the
      transcription level, and there is no information about the breakpoints at the
      genomic level. In the present study, we describe the molecular genetic
      characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases,
      7 of which showed the characteristic t(12;22). As an initial step in the
      characterization of the EWS/ATF1 and ATF1/EWS chimeras, we constructed an
      exon/intron map of the ATF1 gene. The entire ATF1 gene spanned >40 kb and was
      composed of 7 exons. Intron 3, in which most of the genomic breakpoints occurred,
      was to a large extent (83%) composed of repetitive elements. RT-PCR amplified
      EWS/ATF1 cDNA fragments in all patients and ATF1/EWS cDNA fragments in 6 of 10
      patients. Four types of EWS/ATF1 chimeric transcript, designated types 1-4, were
      identified. The most frequent chimeric transcript (type 1) was an in-frame fusion
      of exon 8 of EWS with exon 4 of ATF1. This was the only chimeric transcript in 5
      patients but found together with other variants in 3 tumors. The type 2
      transcript of EWS/ATF1, an in-frame fusion of exon 7 of EWS with exon 5 of ATF1,
      was detected in 4 patients, as the only transcript in 1 case and together with
      other variants in 3 cases. An in-frame fusion of exon 10 of EWS with exon 5 of
      ATF1 (type 3) was found in 1 patient as the only transcript, and an out-of-frame
      fusion of EWS exon 7 with ATF1 exon 7 (type 4) was detected in 1 patient together
      with type 1 and type 2 transcripts. Sequencing of the amplified ATF1/EWS cDNA
      fragments showed in 5 patients that ATF1 exon 3 was fused with EWS exon 10,
      resulting in an out-of-frame chimeric transcript. In 1 case, nt 428 of ATF1 (exon
      4) was fused with EWS exon 8; at the junction, there was an insertion of 4
      nucleotides, also resulting in an out-of-frame transcript. Genomic extra long PCR
      and sequence analysis mapped the genomic breakpoints to introns 7, 8 and 9 of EWS
      and intron 3 and exon 4 of ATF1. While a simple end-to-end fusion was observed in
      2 cases, additional nucleotides were found at the junctions in 2 other cases. In
      addition, topoisomerase I consensus sequences were found close to the junctions,
      suggesting that this enzyme may participate in the genesis of the EWS/ATF1
      fusion.

PMID- 11992547
TI  - A HLA-A2 restricted human CTL line recognizes a novel tumor cell expressed p53
      epitope.
AB  - A p53 peptide-specific CTL line was generated through stimulation with autologous
      monocyte-derived dendritic cells (DC) pulsed with wild-type HLA-A2 binding p53
      derived peptides. A p53 peptide-specific CD8(+) CTL line was established from a
      healthy HLA-A2 positive donor. The CTL line was characterized with respect to
      specificity, affinity and killing of cell lines derived from p53 mutated
      spontaneous tumors. The CTL line demonstrated lysis of p53(139-147) pulsed target
      cells and cold target inhibition experiments as well as antibody blocking
      confirmed that the killing was epitope-specific, HLA-A2 restricted and dependent
      on CD8-binding. Interestingly, the affinity of the CTL line was only in the
      micromole per liter range and target cells pulsed with less than 0.01 microM
      peptide were not recognized. Furthermore, 3 HLA-A2(+) p53 mutated tumor cell
      lines were efficiently lysed by the CTL line, indicating that this novel p53
      peptide epitope is endogenously processed and presented by the HLA-A2 molecules
      of the tumor cells. In conclusion, CTL reactivity towards a wild-type p53 peptide
      was revealed through induction with DC pulsed with a pool of HLA-A2 binding p53
      peptides. In addition, the CTL line, which expressed relatively low affinity for
      the HLA-A2/peptide complex, was able to kill 3 different HLA-A2(+) p53 mutated
      tumor cell lines. The present and our previous observations expand the number of
      p53-derived peptides suitable for vaccination protocols for cancer patients with
      p53 positive tumors.

PMID- 11992548
TI  - Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC
      class I-negative and -positive malignant melanoma through augmented NK activity
      and cytotoxic T-cell response.
AB  - Interleukin (IL)-15, a pleiotropic cytokine, is involved in the development and
      maintenance of NK cells and memory CD8+ T cells. We examined the effects of in
      vivo overexpression of IL-15 on protection against 2 types of murine B16 melanoma
      lines, MHC class I-negative B16.44 and MHC class I-positive B16F10 cells, using
      IL-15 transgenic (Tg) mice that we have recently constructed. The tumor growth
      was severely retarded in IL-15 Tg mice after subcutaneous (s.c.) inoculation with
      B16.44 or B16F10 cells. IL-15 Tg mice showed an augmented NK cell activity
      against B16.44 cells, and in vivo depletion of NK cells by anti-asialoGM1 Ab
      treatment abrogated the antitumor activity in IL-15 Tg mice. On the other hand,
      IL-15 Tg mice inoculated with B16F10 cells developed a significant level of CTL
      response against B16F10 cells, and in vivo depletion of CD8+ T cells by anti-CD8
      MAb treatment abrogated the antitumor activity. Thus, overexpression of IL-15
      augmented antitumor activity against different tumors via augmentation of
      different antitumor mechanisms. These results suggest a possible therapeutic
      application of IL-15 for human neoplasms expressing a wide range of MHC class
      molecules.

PMID- 11992549
TI  - Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response
      to chemotherapy in ovarian cancer.
AB  - To define the involvement of p16/CDKN2 and p15/MTS2 tumor-suppressor genes for
      response to chemotherapy in primary epithelial ovarian cancer, we analyzed
      alterations of the gene in 45 patients who were treated with primary
      cytoreductive surgery followed by 6 courses of cis-diamminedichloroplatinum (II)
      (cisplatin)-based combination chemotherapy. Homozygous deletion of p16/CDKN2 and
      p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to
      the chemotherapy was confirmed by finding at second surgery after the
      chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The
      abundance of gene deletion in nonresponders (56%) was significantly higher (p =
      0.0463) when compared to that in responders (18%). Moreover, the deletion of
      genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian
      cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a
      potential indicator for poor chemotherapy response and adverse prognosis in
      ovarian cancer patients.

PMID- 11992550
TI  - Laminin-gamma2 overexpression in head-and-neck squamous cell carcinoma.
AB  - To identify molecular markers for the progression of head-and-neck squamous cell
      carcinoma (HNSCC), we used RNA arbitrarily primed (RAP) PCR to determine the
      qualitative and quantitative differences in gene expression between normal
      epithelial cells, those derived from dysplastic oral mucosa and invasive and
      metastatic HNSCC. Three differentially expressed DNA fragments (RAP20, RAP21,
      RAP26) that were upregulated in a tumor cell line (T45) were identified as being
      regions of the gamma2 subunit of human laminin-5. Northern blot analysis of total
      cellular RNA revealed overexpression of these transcripts in 6 of 7 HNSCC cell
      lines compared with normal epidermal keratinocytes. In contrast, no differences
      were observed in HeLa (cervical carcinoma) or HCT116 (colon carcinoma) cells.
      Immunostaining of HNSCC cells derived from primary (HN4) and metastatic (HN12)
      tumors indicated elevated levels of endogenous laminin-gamma2 protein.
      Furthermore, HNSCC tissues demonstrated strong laminin-gamma2 staining,
      particularly in the peripheral basaloid cells of tumor islands at the invasion
      front. In contrast, only minimal staining of laminin-gamma2 was detected in basal
      cells of the normal epithelium. The data indicate that laminin-gamma2 is
      frequently overexpressed in HNSCCs and derivative cell lines and that its
      overexpression is likely to be useful as a marker of head-and-neck squamous
      malignancy.

PMID- 11992551
TI  - Analysis of p53/BAX in primary colorectal carcinoma: low BAX protein expression
      is a negative prognostic factor in UICC stage III tumors.
AB  - Deregulation of cell death pathways contributes to tumor development and to the
      clinical course of cancer disease. In patients with liver metastases of
      colorectal cancer, we have previously shown that an intact p53/BAX apoptotic
      pathway is a positive prognostic factor. Therefore, the purpose of our study was
      to determine the prognostic value of BAX protein expression and the mutational
      status of its upstream regulator p53 in primary colorectal adenocarcinoma. To
      this end, we analyzed retrospectively tumor samples of 116 patients who underwent
      surgery for colorectal adenocarcinoma and had a follow-up for a minimum of 5
      years or until death (UICC Stage III: 59 patients, UICC Stage IV: 57 patients).
      Tumors were screened for p53 mutations and investigated for BAX protein
      expression. Overall median survival was 17 months. As expected, patients with
      UICC III tumors survived longer than patients with UICC IV tumors: 69 months vs.
      8 months (p < 0.0001). UICC III tumors with high BAX expression were associated
      with a significantly better prognosis (p = 0.009) than BAX low expressing tumors.
      The combined p53/BAX pathway analysis for the UICC Stage III group revealed the
      worst outcome for patients with a disrupted p53/BAX pathway (i.e., BAX low/p53
      mutated; p = 0.004). In contrast, no significant effect of the p53/BAX status on
      survival was found in UICC IV tumors. Our study in primary adenocarcinoma of the
      colorectum shows for the first time that a disrupted p53/BAX pathway is
      associated with a poor clinical outcome in UICC III tumors. These data also
      confirm our previous report on the relevance of an intact p53/BAX pathway in
      liver metastasis of colorectal cancer. Nevertheless, we were not able to confirm
      this finding in the heterogenous subgroup of UICC IV tumors of the colorectum.
      Our study therefore provides the basis for the analysis of defects in p53/BAX
      (and additional genes) in a prospective trial that is the logical basis for
      future risk-adapted therapies.

PMID- 11992552
TI  - Prognostic significance of p53 mutations in colon cancer at the population level.
AB  - Some studies have reported that p53 mutations or certain types of p53 mutation
      are associated with poor prognosis in colon cancer, while other studies have
      failed to show such a relationship. None of these previous studies was population
      based. We therefore evaluated the prognostic significance of p53 mutations in a
      large, population-based study of 1,464 individuals with colon cancer from Utah
      and California. Mutations in exons 5-8 were detected by SSCP analysis, followed
      by sequencing of aberrant bands. p53 mutations were identified in colon cancers
      from 665 of 1,464 (45.4%) individuals. p53 mutations were significantly more
      common in distal tumors (p < 0.01), tumors of relatively high stage (p = 0.04),
      tumors without MSI (p < 0.01) and tumors without Ki-ras mutations (p < 0.01). In
      a univariate analysis, tumors with p53 mutations were associated with a
      significantly worse 5-year survival than those with wild-type p53 (53.4% vs.
      58.8%, p = 0.04); significantly worse prognosis also was seen with missense
      mutations, transitions, transversions, mutations affecting the structure of the
      p53 molecule, mutations within the beta-sandwich motif and mutations in proximal
      tumors. In multivariate analyses, however, the only significant predictors of
      poor prognosis were G245 hot spot mutations (HRR = 2.16, 95% CI 1.06-4.40) and
      p53 mutations in proximal tumors (HRR = 1.34, 95% CI 1.07-1.63). We conclude that
      overall p53 mutational status is not an independent predictor of poor prognosis
      in colon cancer. However, specific classes of mutations, namely, the G245 hot
      spot mutation and mutations in proximal tumors, are related to significantly
      worse survival even after adjusting for age and stage.

PMID- 11992553
TI  - Body mass index in relation to ovarian cancer: a multi-centre nested case-control
      study.
AB  - The incidence of ovarian cancer is up to 10 times higher in Western countries
      than in rural Asia and Africa. One common consequence of a Western lifestyle is
      the development of excessive body weight and obesity. A multi-centre prospective
      study was conducted to investigate the association between body mass index (BMI)
      and ovarian cancer risk. A case-control study was nested within 3 prospective
      cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Information on
      anthropometry, demographic characteristics, medical history and lifestyle was
      obtained at the time of subjects' recruitment in each cohort. Women diagnosed
      with primary, invasive epithelial ovarian cancer from the 3 cohorts (n = 122)
      diagnosed 12 months or later after recruitment into the respective cohort served
      as case subjects. For each case subject, 2 control subjects that matched the case
      subject on cohort, menopausal status, age and date of recruitment were randomly
      identified. Data were analyzed by conditional logistic regression. There was an
      inverse association between BMI and ovarian cancer risk. For increasing quartiles
      of BMI above the lowest, the ORs were 0.62 (0.32-1.21), 0.59 (0.30-1.17) and 0.46
      (0.23-0.92), p = 0.03. Analyses limited to women diagnosed 3 or more years after
      recruitment into the cohorts did not alter these findings. When obese women (BMI
      > 30) were compared to lean women (BMI < or = 23), the inverse association became
      stronger, with an OR of 0.38 (0.17-0.85), p < 0.02. There was some evidence of
      direct association of ovarian cancer with height, which was limited to cancers
      diagnosed before age 55. Our data suggest that increasing body weight may confer
      a protection against ovarian cancer.

PMID- 11992554
TI  - Radiation-induced leukemia risk among those aged 0-20 at the time of the
      Chernobyl accident: a case-control study in the Ukraine.
AB  - A case-control study was conducted to estimate the radiation-induced acute
      leukemia risk for the period 1987-1997 among residents aged 0-20 at the time of
      the Chernobyl accident in the most radioactively contaminated territories of the
      Ukraine (Rivno and Zhytomir regions). Data were collected on 272 leukemia cases
      diagnosed between 1 January 1987 and 31 December 1997. Of these, 98 cases were
      verified and interviewed. Verified cases were compared to 151 randomly selected
      controls matched by age, gender and type of settlement. The mean value of the
      estimated accumulated equivalent dose to the bone marrow was 4.5 mSv, and the
      maximum value was 101 mSv. A statistically significant increased risk of leukemia
      was found among males whose estimated radiation exposure was higher than 10 mSv.
      This association was statistically significant for acute leukemia cases that
      occurred in the period 1993-1997, particularly for acute lymphoblastic leukemia.
      A similar association was found for acute myeloid leukemia, diagnosed in the
      period 1987-1992.

PMID- 11992555
TI  - Variation in breast cancer risk of heterozygotes for ataxia-telangiectasia
      according to environmental factors.
AB  - Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder, characterized
      by progressive neuronal degeneration, immunological deficiency, radio-sensitivity
      and an increased risk of cancer. Although several studies have confirmed that AT
      heterozygosis increases the risk of breast cancer (BC), we do not know how
      exogenous factors affect this risk. We performed an epidemiological study on the
      cancer risks associated with AT heterozygosis in France and explored the
      variation in BC risk according to environmental factors, such as reproductive
      factors and exposure to ionizing radiation. Information on the amount of ionizing
      radiation received by an individual in their lifetime and on their reproductive
      life was collected from the living relatives of 34 AT children (175 female
      relatives). Consistent with previous reports and with our previous estimate on
      the entire retrospective cohort, we found that the risk of developing BC is 3.6
      fold higher among ATM heterozygous women. An increased risk was associated with
      an early age at menarche, a late age at first childbirth, nulliparity,
      premenopausal status and increasing periods of breast cell mitotic activity
      (BCMA) prior to the first childbirth. Age at menarche, age at 1st childbirth and
      BCMA seemed to have a stronger effect in ATM heterozygotes than in non-ATM
      heterozygotes. However, the tests were not all statistically significant (only
      age at 1st childbirth). Surprisingly, the risk of BC decreased when the chest or
      breasts were irradiated. It is difficult to interpret the data because of the
      small sample size, but further investigations should provide a biological
      explanation for the variation in BC risk associated with exogenous factors
      according to ATM heterozygosis status.

PMID- 11992556
TI  - hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of
      stomach cancer risk in Chinese.
AB  - Oxidative stress is involved in many types of DNA damage, e.g., resulting in 8
      hydroxyguanine adducts. Since a human counterpart exists for the yeast gene OGG1
      (hOGG1) encoding an enzyme that repairs 8-hydroxyguanine, its polymorphism,
      Ser(326)Cys, might have potential as a genetic marker for cancer susceptibility.
      To investigate its association with stomach cancer risk and possible interactions
      with environmental factors, we conducted a case-control study of 101 stomach
      cancer cases and 198 controls using PCR-single-strand conformation polymorphism
      and a questionnaire approach. The proportional distribution of the Cys/Cys
      alleles did not differ between stomach cancer cases and controls, but subgroup
      analyses revealed that a frequent drinking habit elevated the odds ratio (OR) for
      stomach cancer in Cys/Cys compared to Ser/Ser and Ser/Cys carriers. The ORs with
      frequent consumption of pickled vegetables and meat tended to be higher in
      Cys/Cys than in Ser/Ser and Ser/Cys carriers, these interactions being on the
      borderline of statistical significance. Our findings suggest that the hOGG1
      Ser(326)Cys polymorphism may alter the impact of some environmental factors on
      stomach cancer development. For confirmation, an additional study with a larger
      number of subjects is now required.

PMID- 11992559
TI  - Pharmacogenetics of lithium prophylaxis in mood disorders: analysis of COMT, MAO
      A, and Gbeta3 variants.
AB  - We studied the possible association between the prophylactic efficacy of lithium
      in mood disorders and the following gene variants: catechol-O-methyltransferase
      (COMT) G158A, monoamine oxydase A (MAO-A) 30-bp repeat, G-protein beta 3-subunit
      (Gbeta3) C825T. A total of 201 subjects affected by bipolar (n = 160) and major
      depressive (n = 41) disorder were followed prospectively for an average of 59.8
      months and were typed for their gene variants using PCR techniques. COMT, MAO-A,
      and Gbeta3 variants were not associated with lithium outcome, even when possible
      stratification effects such as sex, polarity, age at onset, duration of lithium
      treatment, and previous episodes were included in the model. The pathways
      influenced by those variants are not therefore involved with long-term lithium
      outcome in our sample.

PMID- 11992558
TI  - Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in
      mood disorders.
AB  - Variants of the functional polymorphism in the serotonin transporter (upstream
      regulatory region: 5-HTTLPR), the tryptophan hydroxylase (TPH), the monoamine
      oxidase A (MAO-A), and the dopamine receptor D4 (DRD4) genes have all been
      associated with mood disorders. The aim of this study was to test those
      hypotheses by using a family-based association approach. Both diagnoses and
      psychopathology were used for phenotype definitions. A total of 134 nuclear
      families with mood disorders, with probands affected by bipolar (n = 103) or
      major depressive (n = 58) disorders, were included in the study. All subjects
      were typed for the above-mentioned gene variants using polymerase chain reaction
      (PCR) technique. No significant transmission disequilibrium was found in the
      overall sample for any polymorphism. A separate analysis of bipolar subjects
      only, or the use of continuous psychopathologic traits as affectation status did
      not influence the observed results. Our study did not support the involvement of
      5-HTTLPR, TPH, MAO-A, or DRD4 polymorphisms in mood disorders.

PMID- 11992560
TI  - Association study of MAO-A, COMT, 5-HT2A, DRD2, and DRD4 polymorphisms with
      illness time course in mood disorders.
AB  - The aim of our study was to investigate a possible influence of monoamine oxydase
      A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A),
      dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on
      timing of recurrence in mood disorders. Gene variants were determined using PCR
      based techniques in 550 inpatients affected by recurrent mood disorders (major
      depressives: n = 212; bipolars: n = 338), rapid cycling mood disorder (n = 81),
      and 663 controls. We investigated possible genetic influences by comparing
      illness time course of subjects subdivided according to genotype using
      multivariate analysis of variance (MANOVA). We could not observe a significantly
      different time course. No demographic and clinical variables such as sex, age or
      polarity of onset, presence of psychotic features, genetic loading, or education
      level influenced the observed results. Our results suggest that MAO-A, COMT, 5
      HT2A, DRD2, and DRD4 gene variants are not involved in susceptibility toward
      different time courses in mood disorders.

PMID- 11992561
TI  - Endophenotypes in bipolar disorder.
AB  - The search for genes in bipolar disorder has provided numerous genetic loci that
      have been linked to susceptibility to developing the disorder. However, because
      of the genetic heterogeneity inherent in bipolar disorder, additional strategies
      may need to be employed to fully dissect the genetic underpinnings. One such
      strategy involves reducing complex behaviors into their component parts
      (endophenotypes). Abnormal neurophysiological, biochemical, endocrinological,
      neuroanatomical, cognitive, and neuropsychological findings are characteristics
      that often accompany psychiatric illness. It is possible that some of these may
      eventually be useful in subdefining complex genetic disorders, allowing for
      improvements in diagnostic assessment, genetic linkage studies, and development
      of animal models. Findings in patients with bipolar disorder that may eventually
      be useful as endophenotypes include abnormal regulation of circadian rhythms (the
      sleep/wake cycle, hormonal rhythms, etc.), response to sleep deprivation, P300
      event-related potentials, behavioral responses to psychostimulants and other
      medications, response to cholinergics, increase in white matter hyperintensities
      (WHIs), and biochemical observations in peripheral mononuclear cells. Targeting
      circadian rhythm abnormalities may be a particularly useful strategy because
      circadian cycles appear to be an inherent evolutionarily conserved function in
      all organisms and have been implicated in the pathophysiology of bipolar
      disorder. Furthermore, lithium has been shown to regulate circadian cycles in
      diverse species, including humans, possibly through inhibition of glycogen
      synthase kinase 3-beta (GSK-3beta), a known target of lithium.

PMID- 11992562
TI  - Apparent replication of suggestive linkage on chromosome 16 in the NIMH genetics
      initiative bipolar pedigrees.
AB  - Analyses of a replication sample of families collected as part of the National
      Institute of Mental Health (NIMH) Genetics Initiative for bipolar disorder
      provide further evidence for linkage to a region of chromosome 16. Families who
      had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar
      type (SABP) first-degree relative were ascertained for the purpose of identifying
      genes involved in bipolar affective disorder. A series of hierarchical models of
      affected status was used in linkage analyses. Initial genetic analyses of
      chromosomes 3, 5, 15, 16, 17, and 22, completed at Indiana University in 540
      subjects from 97 families, suggested evidence of linkage to chromosomes 5, 16,
      and 22 [Edenberg et al., 1997: Am J Med Genet 74:238-246]. Genotyping was
      subsequently performed on these chromosomes in a replication sample of 353
      individuals from 56 families. Nonparametric linkage analyses were performed using
      both affected relative and sibling pair methods. Analyses in the new sample on
      chromosome 16, using the broadest model of affected status, corroborate
      previously reported suggestive linkage to the marker D16S2619. Combining the
      initial and replication samples further increased the evidence of linkage to this
      region, with a peak lod score of 2.8.

PMID- 11992563
TI  - Genome survey for susceptibility loci for recurrent, early-onset major
      depression: results at 10cM resolution.
AB  - Recurrent (two or more episodes), early-onset (first episode at < or = 25 years)
      major depressive disorder (RE-MDD) is a strongly familial condition (lambda(first
      degree relatives) = 8) whose malignant effects have a significant negative impact
      on the health and longevity of patients and their family members. The goal of
      this study was to identify candidate susceptibility loci that influence the
      development of RE-MDD. We completed a systematic survey of the human genome,
      conducted at an average resolution of 10 cM, for the identification of simple
      sequence tandem repeat polymorphisms (SSTRPs) that target susceptibility genes
      for RE-MDD by virtue of linkage disequilibrium. The efficiency of our association
      study was enhanced by genotyping pools of DNA from 100 adults with RE-MDD and 100
      adult controls who had no personal or family history of mental disorders. Both
      groups included equal numbers of Caucasian men and women and were matched as
      closely as possible for age and ethnicity. Allelic associations with RE-MDD were
      observed for 19 of the 387 SSTRPs in the CHLC Human Screening Set/Weber Version
      9. Sixteen of the 19 candidate susceptibility loci revealed significant allelic
      associations with RE-MDD in men (n = 7) or women (n = 9), but not in both sexes.
      Evidence for both risk and protective alleles was detected. Two of the candidate
      susceptibility loci reside within several Mb of loci previously reported
      megabases to be linked to "comorbid alcoholism and depression" in families of
      individuals with alcoholism and to a broadly defined affected phenotype that
      included recurrent major depression in the families of patients with bipolar
      disorder. Although it has been suggested that the genes that influence risk for
      MDD in the two sexes may not be entirely the same, the results of our study
      suggest that sex specificity of susceptibility loci for RE-MDD may be the rule
      rather than the exception. The observed preponderance of sex-specific
      susceptibility loci for RE-MDD suggests that there may be important differences
      in the molecular pathophysiology of RE-MDD in men and women. Alternatively, our
      findings may reflect the existence of sex-specific differences in the molecular
      mechanisms that determine resilience to endogenous or environmental depressogenic
      stimuli.

PMID- 11992564
TI  - Lack of an association between 5-HT1A receptor gene structural polymorphisms and
      suicide victims.
AB  - A serotonergic dysfunction in the brain has been reported to be involved in
      suicidal behavior independently of the presence of a specific psychiatric
      disorder. Serotonin 1A (5-HT1A) receptors are known to be located on serotonergic
      nerve terminals and to be involved in the presynaptic regulation of serotonin
      release. Genetic factors partly explain the risks for suicide, and a suicide
      completion group is thought to be more uniform than a suicide attempt group. To
      explore the hypothesis that the 5-HT1A receptor-induced serotonergic dysfunction
      is implicated genetically in suicide, we focused on the structural polymorphisms,
      Pro16Leu and Gly272Asp, of the 5-HT1A receptor gene, and examined the association
      between suicide victims who completed suicide and these two polymorphisms. In
      both polymorphisms, we found no significant difference in genotype distribution
      or allele frequencies between suicide victims and controls. These findings
      suggest that neither of these two polymorphisms is associated with suicide
      victims and it is unlikely that the 5-HT1A receptor gene is implicated in the
      susceptibility to suicide.

PMID- 11992565
TI  - Estrogen receptor 1 gene (ESR1) variants in panic disorder.

PMID- 11992567
TI  - Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype
      association study in Japanese cases.
AB  - Interleukin-6 (IL-6), an inflammatory cytokine might be involved in the
      pathophysiology of Alzheimer disease (AD); several studies have reported that the
      "C allele of IL-6 variable number of tandem repeat polymorphism" (IL-6vntr)
      delayed initial onset of AD and also decreased its risk per se. Another
      polymorphism, G/C allele of IL-6 gene promoter region (IL-6prom), is also a
      candidate because it has an influence on the regulation of plasma IL-6
      concentration. We examined these IL-6 polymorphisms in 128 Japanese AD cases and
      83 control cases using a PCR-RFLP method. The results showed the frequency of the
      IL-6prom G allele was significantly increased in AD, although IL-6vntr
      polymorphism was not. Plasma IL-6 concentration of the AD cases was also
      significantly higher than that of the control cases. Moreover, the IL-6prom G
      allele-positive AD patients showed a tendency to have higher IL-6 concentration
      in the AD group. These findings suggest that the IL-6prom G allele which may
      affect plasma IL-6 concentration might be a risk factor for sporadic AD in
      Japanese.

PMID- 11992566
TI  - Potentially functional polymorphism in the promoter region of prodynorphin gene
      may be associated with protection against cocaine dependence or abuse.
AB  - It has been demonstrated that the opioid peptide dynorphin plays a role in
      modulating responses to several psychoactive substances including cocaine. Our
      laboratory and others have found that mRNA levels of dynorphin in the caudate and
      putamen are elevated after acute or chronic cocaine exposure in rats. Recently, a
      68-base pair (bp) repeat polymorphism within the core promoter region of the
      human prodynorphin gene has been reported to occur in alleles containing one,
      two, three, or four copies. This repeat contains a putative AP-1 transcription
      factor binding site; reporter gene constructs with three or four, but not one or
      two, copies of the tandem repeats were shown to be associated with increases in
      transcriptional activation in in vitro cellular assays. We hypothesize that this
      polymorphism may be associated with individual differences in vulnerability to
      cocaine dependence or abuse. From an ongoing study of the genetics of addiction,
      174 subjects were studied, including individuals with a primary diagnosis (DSM-IV
      criteria) of cocaine dependence (N = 61) or abuse (N = 22), and controls with no
      history of any substance dependence or abuse (N = 91). We designed primers for
      polymerase chain reaction (PCR) to amplify sequences of the promoter region of
      the prodynorphin gene containing the repeat element. The association of alleles
      containing three or four repeats with cocaine dependence/abuse was examined. With
      data stratified by ethnic group, pooled relative risk (RR) with Mantel-Haenszel
      Chi square was calculated: RR = 0.59 (95% confidence interval 0.37-0.95), chi2
      (1) = 4.14, P = 0.042. Our results suggest that this allelic variation at the
      promoter region of the prodynorphin gene (alleles with three or four repeats),
      which may result in enhanced transcription of the gene, may contribute to
      relative protection and decrease individual vulnerability to develop cocaine
      dependence or abuse.

PMID- 11992568
TI  - No association between DCP1 genotype and late-onset Alzheimer disease.
AB  - In a study of 261 patients with Alzheimer disease (AD) and 306 cognitively normal
      control subjects from Germany, Switzerland, and Italy, we found no association
      between genotype counts or allelic frequencies of DCP1, the gene encoding
      angiotensin-converting enzyme. In accordance with several other studies, our data
      could not confirm previous association findings. Critical review about all
      studies available on DCP1 genotyping and AD, age-associated cognitive decline,
      longevity, and other conditions revealed remarkable inconsistencies. Several
      studies showed significant deviations of genotype counts from Hardy Weinberg
      equilibrium (HWE). Deviations from HWE may limit the comparability of study
      results and require clarification before drawing conclusions with respect to
      disease risk, health conditions, or longevity in association with DCP1 genotype.

PMID- 11992569
TI  - Genetic study of apolipoprotein E gene, alpha-1 antichymotrypsin gene in sporadic
      Parkinson disease.
AB  - Several lines of evidence have suggested some common genetic risk factors for
      Alzheimer disease (AD) and Parkinson disease (PD) because there are some
      overlapping pathologies in these two neurodegenerative diseases. In the present
      study, we investigated the role of Apolipoprotein E gene polymorphism and the
      signal peptide polymorphism in alpha-1 antichymotrypsin (ACT) gene in idiopathic
      sporadic PD. The study was performed in a sample consisting of 68 PD cases and
      160 healthy subjects in Shanghai China. We found no significant differences of
      ACT gene polymorphic distribution between PD cases and controls. The ApoE gene
      epsilon2/epsilon4 genotype was significantly more frequent in PD subjects (chi2 =
      7.126, df = 1, P = 0.008) and conferred a 12.70 times susceptibility for PD (OR =
      12.62, 95% CI: 1.445-110.17, chi2 = 5.259, P < 0.05, AF = 4.59%). No interaction
      of ApoE and ACT genes was detected in PD. Therefore, our data suggested that the
      ApoE epsilon2/epsilon4 genotype might be a susceptibility variant of moderate
      effect for sporadic idiopathic PD in our samples, whereas the ACT gene signal
      peptide polymorphism might not.

PMID- 11992570
TI  - Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to
      chromosome 7q22-q32.
AB  - The autosomal dominant (AD) spinocerebellar ataxias (SCAs) and hereditary sensory
      neuropathies (HSN) are heterogeneous disorders characterized by variable
      clinical, electrophysiological, and neuropathological profiles. The SCAs are
      clinically characterized by slowly progressive incoordination of gait often
      associated with poor coordination of hands, speech, and eyes. Peripheral
      neuropathy is not a frequent part of the SCA syndrome. In contrast, the HSNs are
      primarily characterized by progressive sensory loss. There is substantial
      clinical overlap between the various SCAs and the various HSNs, and they often
      cannot be differentiated on the basis of clinical or neuro-imaging studies. We
      have identified a five-generation American family of Irish ancestry with a unique
      neurological disorder displaying an AD pattern of inheritance. There was variable
      expressivity and severity of symptoms including sensory loss, ataxia, pyramidal
      tract signs, and muscle weakness. Nerve conduction studies were consistent with a
      sensory axonal neuropathy. Muscle biopsy revealed neurogenic atrophy and brain
      MRI showed mild cerebellar atrophy. To identify the responsible locus we pursued
      a whole genome linkage analysis. After analyzing 114 markers, linkage to D7S486
      was detected with a two point LOD score of 4.79 at theta = 0.00. Evaluation of
      additional markers in the region provided a maximum LOD score of 6.36 at theta =
      0.00 for marker D7S2554. Haplotype analysis delimited an approximately 14-cM
      region at 7q22-q32 between markers D7S2418 and D7S1804 cosegregating with the
      disease. Because this disorder does not easily fall into either the SCA or HSN
      categories, it is designated sensory/motor neuropathy with ataxia (SMNA).

PMID- 11992571
TI  - Cognitive and behavioral performance among FMR1 high-repeat allele carriers
      surveyed from special education classes.
AB  - The fragile X syndrome is caused by an unstable CGG repeat sequence in the 5'
      untranslated region of the X-linked, FMR1 gene. When the number of repeats
      exceeds 200, the region is hypermethylated and the gene is silenced. The lack of
      the protein produced by the FMR1 gene, FMRP, causes the fragile X syndrome.
      Recent evidence suggests that FMR1 alleles with unmethylated long repeat tracks
      (40-200 repeats) may cause a specific somatic phenotype in women, premature
      ovarian failure, and may cause variation in the levels of FMR1 mRNA and FMRP.
      Because FMR1 is known to be involved in the regulation of subset of genes
      expressed in the brain, we investigated the variation in cognitive and/or
      behavioral performance among carriers of high repeat alleles. Specifically, we
      administered cognitive, behavioral, and adaptive performance tests to children
      identified with high repeat alleles who attended special education classes in
      Atlanta, Georgia public schools and to those with < 40 repeats drawn from the
      same population. Overall, we found no significant effect of repeat size and the
      psychometric measures in our test battery after adjustment for multiple
      comparisons. All scales were found to be within 1 SD standard deviation of the
      mean. We did find an intriguing, albeit marginally statistically significant,
      association in the cognitive profile among males and not females, consistent with
      an X-linked effect. After adjusting for the overall cognitive abilities score,
      Verbal Ability scores decreased and Nonverbal Reasoning scores increased with
      repeat number to a greater extent in males than females. Spatial Ability scores
      were not associated with repeat number.

PMID- 11992572
TI  - Investigation of two variants in the DOPA decarboxylase gene in patients with
      autism.
AB  - Though genetic risk factors are important for the development of autism, no
      specific risk alleles have yet been identified. DOPA decarboxylase (DDC) is
      involved in both the catecholaminergic and serotonergic pathways and may be
      considered a functional candidate gene for autism. The present study is the first
      to test if two new variants of possible functional significance in the DDC gene
      increase the susceptibility to autism. A total of 90 parent-offspring trios
      recruited in Denmark and France were investigated using the transmission
      disequilibrium test (TDT). We found no evidence of linkage disequilibrium between
      autism and either of the two polymorphisms. Nor did we find linkage
      disequilibrium between autism and haplotypes of the two variants using a
      multiallelic TDT. These findings suggest that the DDC gene is unlikely to play a
      major role in the development of autism in our data set.

PMID- 11992573
TI  - Familial aggregation of dyslexia phenotypes. II: paired correlated measures.
AB  - Dyslexia is a common and complex behavioral disorder characterized by unexpected
      difficulty in learning to read. Psychometric measures used to assess dyslexia
      often evaluate overlapping processes or abilities. To identify subphenotypes
      amenable to model-based linkage analyses, we have used careful language
      phenotyping, familial aggregation analyses of single phenotype measures, and
      segregation analyses. In the current study, to identify covariates to use in
      future segregation analyses we examined six pairs of related measures selected
      from among the most promising candidates in the initial aggregation analyses
      whose aggregation patterns were most consistent with a genetic basis. For these
      reciprocal aggregation analyses each measure is evaluated with the paired measure
      as the covariate to obtain information about the interdependence of the paired
      measures on shared genetic factors. Six pairs of measures were evaluated: 1)
      accuracy and efficiency of phonological decoding; 2) phonological nonword memory
      and written spelling; 3) phonological decoding accuracy and written spelling; 4)
      inattention ratings and rapid automatized naming for switching letters and
      numerals (RAS); 5) inattention ratings and oral reading rate; and 6) RAS and oral
      reading rate. Results of these analyses provide evidence that there may be a
      genetic contribution to efficiency of phonological decoding in addition to the
      genetic contribution it shares with accuracy of phonological decoding, a genetic
      contribution to phonological nonword memory in addition to the genetic
      contribution it shares with written spelling, a genetic contribution to written
      spelling in addition to the genetic contribution it shares with accuracy of
      phonological decoding, and a genetic contribution to inattention ratings in
      addition to the genetic contribution it shares with either RAS or oral reading
      rate.

PMID- 11992574
TI  - Mother-to-infant transmission of hepatitis C virus: rate of infection and
      assessment of viral load and IgM anti-HCV as risk factors.
AB  - One hundred twenty-six mother-infant couples were studied and 105 exposed babies
      were monitored for at least 12 months to define the risk of mother-to-infant HCV
      transmission. Infection occurred in 5 out of 76 infants (6.6%) born to 69
      viraemic mothers and in none of 29 born to 26 non-viraemic mothers. Only one
      child was HCV RNA positive one month after birth, while the remaining children
      became positive at the 3rd to 4th month. HCV genotypes of the babies matched
      those of their mothers. No difference was found between women who transmitted the
      virus and those who did not with regard to age, history of drug abuse, HIV
      infection, ALT abnormal values, HCV genotype, type of delivery, and breast
      feeding. Four out of 5 infected infants were born to mothers with IgM anti-HCV (P
      = 0.04). The mean viral titre in transmitting women (10(7.2)) was higher than in
      non-transmitting (10(6.5)), and the proportion of mothers with viral load > or =
      10(7) was statistically higher in transmitting than non-transmitting women (P =
      0.03). These data show that HCV perinatal infection is a rare event and suggest
      that IgM positivity and high viral load (> or = 10(7)) in the mother are
      independent variables correlated with HCV transmission (O.R. = 14.5; 95% CI: 1.3
      160.7 and O.R. = 16.3; 95% CI: 1.5-179.9, respectively).

PMID- 11992575
TI  - Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV
      infection.
AB  - Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co
      infected patients with controlled human immunodeficiency virus (HIV) infection
      and correlated with clinical, biological, and histological parameters. Thirty
      seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A)
      and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had
      HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients
      but two were receiving antiretroviral treatment. Liver tissue and sera were used
      for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had
      serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003).
      Intrahepatic HCV load did not depend on age, sex, duration of HCV infection,
      CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV
      load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower
      levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026).
      Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)
      treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak
      but significant correlation between serum and liver HCV RNA was found. The amount
      of hepatic HCV RNA was correlated with AST levels, histological activity, but not
      with HCV genotype or fibrosis. The immune improvement associated with PI regimens
      could help reduce HCV load, supporting a protective effect of PI-induced immune
      restoration.

PMID- 11992576
TI  - Dendritic cell susceptibility to hepatitis C virus genotype 1 infection.
AB  - In vitro infection of human monocyte-derived dendritic cells was carried out to
      study their susceptibility to hepatitis C virus (HCV) infection. Immature
      dendritic cells and mature dendritic cells were incubated overnight at 37 degrees
      C with HCV-positive (genotype 1) serum samples; the presence of the viral genome
      associated with the production of its replicative intermediate was used as
      evidence of infection. In immature dendritic cells, HCV RNA was detectable from
      days 1-10 post-infection (p.i.), and de novo synthesis of negative-strand HCV RNA
      could be demonstrated by a strand-specific rTth reverse transcription-polymerase
      chain reaction at day 2. In mature dendritic cells, the positive-strand form was
      detectable from days 1-5 p.i., while the negative-strand HCV RNA appeared at days
      1 and 2 p.i. Quasispecies present in the inoculum and 6 days p.i. were analyzed
      by sequencing hypervariable region 1 of the E2 protein. Only two of seven HVR
      variants present in the inoculum were found in HCV-infected immature dendritic
      cells. Another two HVR variants not found in the inoculum were recovered from
      infected immature dendritic cells, suggesting serum minor variants selection or
      virus evolution during in vitro replication. Analysis by single-strand
      conformation polymorphism assay of 5' untranslated region of HCV sequences showed
      that the patterns obtained from the inoculum and infected immature dendritic
      cells and mature dendritic cells differed slightly. These findings indicate that
      both immature dendritic cells and mature dendritic cells are susceptible to HCV
      genotype 1 infection, supporting at least HCV RNA replication. This model should
      be a valuable tool for the study of modulation of dendritic cell functions in HCV
      infection.

PMID- 11992577
TI  - Increased frequency of IFN-gamma-producing peripheral CD8+ T cells with memory
      phenotype in patients with chronic hepatitis C.
AB  - To identify the capacity for cytokine production and the phenotypic
      characteristics of peripheral CD8(+) T cells in patients with chronic hepatitis
      C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at
      the single cell level by three-color flow cytometry. Whole blood was stained with
      surface CD8, intracellular interferon-gamma (IFN-gamma), and interleukin-4 (IL
      4), surface CD8, CD28, and intracellular IFN-gamma after stimulation with PMA
      plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-gamma-producing
      peripheral CD8(+) T cells were found frequently in patients than in controls (P <
      0.05), whereas IL-4-producing peripheral CD8(+) T cells were not. Although the
      frequency of peripheral CD28(+)CD8(+) and CD28(-)CD8(+) T cells in patients was
      not different from that of controls, CD28(+)CD8(+) T cells exceeded CD28(-)CD8(+)
      T cells in the capacity for IFN-gamma-production after mitogenic stimulation (P <
      0.01). In a more detailed analysis of the CD28(+)CD8(+) T cells, CD45RA(
      )CD28(+)CD8(+) T cells, defined phenotypically as memory cells, were found
      frequently in patients than in controls (P < 0.05). There were no significant
      correlations between the frequency of IFN-gamma-producing peripheral CD8(+) T
      cells and hepatitis C virus RNA level or serum alanine aminotransferase level in
      patients. These data suggest that functionally T cytotoxic type 1 and memory
      CD8(+) T cells are predominant in the peripheral blood of chronic hepatitis C
      patients and that such activated CD8(+) T cells are associated with liver damage.

PMID- 11992579
TI  - Immunisation of Balb/c mice with severely attenuated murine cytomegalovirus
      mutants induces protective cellular and humoral immunity.
AB  - Previously, we showed that two temperature-sensitive mutants of murine
      cytomegalovirus (tsm5 and tsm30) expressed immediate-early (IE-1), early (E-1),
      and late (gB) phase genes in the tissues of immunocompetent Balb/c mice, yet
      failed to produce infectious progeny virus in any tissue at any time at 1-21 days
      post-infection. Mice inoculated intraperitoneally with tsm5 became latently
      infected, but this latent virus could not be reactivated as an infectious virus
      after immunosuppression, although all three transcripts were produced.
      Immunocompetent mice infected with tsm30 did not become latently infected. In the
      present study, immunodeficient SCID mice supported productive infection of both
      mutants, suggesting that low-level viral replication does occur in
      immunocompetent mice, but that it is limited by the host immune response. This is
      supported by the observation that immunocompetent mice were protected against
      virulent K181 challenge even after immunisation with as few as 40 pfu of mutant
      virus, whereas UV-inactivated mutant or K181 virus was not immunoprotective at
      doses of 40,000 pfu. Immunity induced by subcutaneous inoculation was also
      protective, whereas that induced by intragastric immunisation was not. Protection
      was lifelong (18 months). Although tsm5 induced high antibody titres, there was
      little evidence of an antibody response to tsm30. In contrast, a significant
      CD8(+) CTL response to the Balb/c immunodominant IE-1 nonapeptide (YPHFMPTNL) was
      elicited by both mutants, as determined by an interferon-gamma ELISPOT assay,
      although this response was lower than that induced by K181 infection. In
      addition, CTLs specific for m04 (YGPSLYRRF) and M84 (AYAGLFTPL) peptides could be
      detected at low frequency after K181, tsm5, and tsm30 immunisation. Such
      protective immunity did not prevent the challenge K181 virus from entering the
      latent state, but it appeared to reduce the frequency of reactivation.

PMID- 11992578
TI  - Hemorrhagic fever occurs after intravenous, but not after intragastric,
      inoculation of rhesus macaques with lymphocytic choriomeningitis virus.
AB  - Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs,
      but these viruses are not highly pathogenic for most rodent carriers. In the
      United States, arenaviruses precipitated outbreaks of hepatitis in captive
      monkeys, and they present an emerging health threat in the tropical areas of
      Africa and South America. We describe infection of rhesus macaques with the
      prototype arenavirus, lymphocytic choriomeningitis virus (LCMV), using the WE
      strain that has been known to cause both encephalopathy and multifocal
      hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and
      three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys
      developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.
      inoculated monkeys had an attenuated infection with no disease. Pathological
      signs of the primate i.v. infection differ significantly from guinea pig
      arenavirus infections and make this a superior model for human viral hemorrhagic
      disease.

PMID- 11992580
TI  - Human cytomegalovirus as a direct pathogen: correlation of multiorgan involvement
      and cell distribution with clinical and pathological findings in a case of
      congenital inclusion disease.
AB  - The human cytomegalovirus (HCMV), a member of the Herpesviridae, is the most
      frequent cause of congenital virus infections and a major cause of morbidity and
      mortality in immunocompromised patients. Due to the lack of an appropriate animal
      model, insight into the pathogenesis of HCMV infections originates primarily from
      in situ examination of HCMV-infected tissues. Although in immunocompromised
      adults such tests are complicated frequently by the presence of additional
      misleading pathogens, the absence of additional pathogens renders congenital
      inclusion disease the most suitable access for investigation of pathogenetic
      aspects of HCMV infections. Immunohistochemical examination of tissue sections
      from a boy with fatal congenital inclusion disease was undertaken to detect the
      extent of multiorgan and cell involvement. Adrenal gland, bone marrow,
      diencephalon, heart, kidney, liver, lung, pancreas, placenta, small bowel and
      spleen were included in this study. Detection of virus antigens from different
      phases of viral replication revealed that all investigated organs were infected
      by HCMV. Simultaneous detection of cell type specific marker molecules showed
      that a variety of cell types stained positive for HCMV antigens including
      endothelial cells, epithelial cells, smooth muscle cells, mesenchymal cells,
      hepatocytes, monocytes/macrophages and granulocytes. The lung, the pancreas, the
      kidneys and the liver were the major target organs with a high number of HCMV
      infected cells. This correlated with multiorgan failure as the cause of death and
      strongly indicates direct pathogenetic effects of HCMV.

PMID- 11992581
TI  - Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus
      monkeys with enterovirus 71.
AB  - Among the enteroviruses, polioviruses and enterovirus 71 (EV71) are two major
      neurotropic viruses causing serious neurological manifestations. While
      polioviruses are being eradicated globally by vaccination, EV71 still has the
      potential to cause a large outbreak such as that in Taiwan in 1998, in which
      there were many fatalities. In this study, we determined the neurovirulence of
      EV71 by neuropathological analysis of cynomolgus monkeys after experimental
      infection with five EV71 strains, which were isolated from individual patients
      with fatal encephalitis; meningitis; and hand, foot, and mouth disease. After
      intraspinal inoculation, the monkeys developed neurological manifestations within
      1-6 days post-inoculation, irrespective of the inoculated strains. These
      manifestations included not only pyramidal tract signs such as flaccid paralysis,
      but also extrapyramidal tract signs such as tremor and ataxia. Histological and
      viral examinations confirmed virus replication in the spinal cord, brainstem,
      cerebellar cortex, and dentate nuclei, and cerebrum. The strains isolated during
      the 1970s and 1990s showed no particular differences with respect to
      neurotropism. Thus, it is clear that EV71 has a wider neurotropism than that of
      polioviruses.

PMID- 11992582
TI  - Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak
      in Taiwan.
AB  - In 1998, an epidemic of hand-foot-and-mouth disease and herpangina caused by
      enterovirus 71 occurred in Taiwan, leaving many fatalities and severely
      handicapped survivors in its wake. The reasons this rather common pathogen would
      cause such a large-scale epidemic remain unknown. A seroepidemiological survey to
      elucidate the epidemiological characteristics of this outbreak, including its
      incidence and case-fatality rates was undertaken. Microneutralization tests for
      antibodies against enterovirus 71 were used to screen four collections of serum
      samples: 1) 202 specimens taken from individuals > or = 4 years old in 1994; 2)
      245 specimens collected from individuals of all ages in 1997; 3) 1,258 specimens
      collected from individuals of all ages in 1999; and 4) sera samples from a birth
      cohort of 81 children who had yearly blood samples taken from 1988-98. After the
      maternal antibody had declined, the seropositive rates began to increase with
      age. Approximately half of all children aged 6 years or older were enterovirus 71
      seropositive. Significantly higher seropositive rates were noted in 1999 than in
      1997, in children aged 0.5-3 years. The incidence of enterovirus 71 infection
      during the epidemic was estimated to be 13-22%, with the higher rates in younger
      children. The case-fatality rate was highest (96.96 per 100,000) in infants aged
      6-11 months, and declined in older children. The results showed that enterovirus
      71 is endemic in Taiwan. The apparent lack of large-scale enterovirus 71 activity
      in the 3 years before 1998 might have been the prelude to the epidemic's
      appearance in 1998, and might suggest that enterovirus 71 infection will reappear
      every few years. The lack of a protective antibody in younger children may
      account for the high incidence and case-fatality rate in this age group.

PMID- 11992583
TI  - Comparative analysis of two coxsackievirus B3 strains: putative influence of
      virus-receptor interactions on pathogenesis.
AB  - Strain-specific differences in the interaction of coxsackievirus B3 (CVB3) with
      the coxsackievirus-adenovirus receptor (CAR) and the decay-accelerating factor
      (DAF) co-receptor proteins were investigated using a non-haemagglutinating (CVB3)
      and a haemagglutinating (CVB3-HA) strain of CVB3. A panel of receptor-transfected
      hamster CHO cells, expressing either CAR (CHOCAR cells), DAF (CHODAF cells), or
      both receptor proteins (CHODC cells) were used to study the interplay of CAR and
      DAF receptor molecules with regard to binding and infection with CVB3 and CVB3
      HA. Despite clear differences in their binding phenotypes, both virus strains
      were found to primarily depend on the CAR receptor protein for initialization of
      productive infections. Cytopathic effects induced by CVB3-HA were influenced by
      co-expression of DAF receptor proteins. The cardiotropic potential of both virus
      strains was investigated in A.BY/SnJ mice. Despite comparable virus replication
      of both CVB3 strains in individual myocytes, the number of infected heart muscle
      cells was significantly lower in CVB3-HA infected mice. Infections of pancreata
      correlated with myocardial infections. Together these data suggest that even
      small differences in virus-receptor interactions, influencing virus binding and
      virus spread, may have an impact on the pathogenesis of CVB-induced diseases.

PMID- 11992584
TI  - Single-cell cytokine analysis allows detection of cervical T-cell responses
      against human papillomavirus type 16 L1 in women infected with genital HPV.
AB  - Specific types of human papillomavirus (HPV) are known to play a causal role in
      the development of cervical cancer, with human papillomavirus type 16 (HPV-16)
      identified as the predominant type. Despite this, little is known about cervical
      immune responses to this pathogen. The aim of this study was to assess the
      feasibility of cervical cytobrush sampling and single-cell cytokine staining to
      investigate cervical lymphocyte-specific cytokine responses to HPV-16 antigens.
      Of eighteen women recruited into the study, five were HPV DNA positive at the
      cervix (current exposure) and a further five had circulating antibodies to HPV-16
      (previous exposure). Cervical lymphocytes, isolated from the five HPV DNA
      positive women, two HPV DNA-negative controls, and one woman with circulating HPV
      16 antibodies were assessed for HPV-specific responses using intracellular
      staining for interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). We
      demonstrate that both CD4(+) and CD8(+) cervical T lymphocytes, harvested from
      noninfected and infected subjects, produce these cytokines in response to
      nonspecific stimulation. However, antigen-specific (HPV-16 L1) IFN-gamma
      production by CD4(+) and CD8(+) cervical T lymphocytes is only detectable in
      women exposed currently or previously to HPV-16. This is the first time that
      antigen-specific cytokine responses of mucosal lymphocytes, obtained from a site
      of HPV infection, have been demonstrated. This finding clearly illustrates the
      use of intracellular cytokine staining for investigation of low precursor
      frequency single-cell antigen-specific responses in lymphocytes harvested from
      mucosal sites with HPV infection.

PMID- 11992585
TI  - Local treatment of HPV-induced skin lesions by Cidofovir.
AB  - Human papillomavirus (HPV) induced epithelial cell proliferation is responsible
      for a broad range of lesions. Treatment of such lesions is characterized by a
      high relapse rate. Four patients are described who were treated locally with
      cidofovir (cream 1% or injection of 2.5 mg/ml solution) for multi-treated
      relapsing HPV-associated lesions. Three of the four patients had a complete
      response. The fourth patient showed a clinical response in the first cycle of
      treatment, but new lesions appeared during four successive cycles of cidofovir.

PMID- 11992586
TI  - Detection and genotyping of human papillomavirus DNA by SPF10 and MY09/11 primers
      in cervical cells taken from women attending a colposcopy clinic.
AB  - Human papillomavirus (HPV) is the main etiological agent of cervical cancer.
      There is a large number of HPV genotypes and therefore a need to distinguish the
      high risk HPV genotypes associated with invasive cancer from the low risk.
      Because persistence of high risk HPV infection is necessary for progression of a
      pre-invasive cervical change one needs to identify the individual genotype to see
      if it persists. PCR amplification of HPV DNA is described using two consensus
      primer systems from cervical cells. Amplified HPV DNA was genotyped using a
      reverse hybridization line probe assay (LiPA). HPV DNA was amplified from 42% of
      samples by MY09/11 and from 80% by SPF10. In 42 samples HPV DNA was detected by
      both primer sets and in 38 samples only the SPF10 primers detected HPV DNA. The
      LiPA detected 21 different HPV genotypes (13 high risk) in this cohort of
      samples. Forty-three percent contained a single HPV genotype and 24% contained
      multiple infections (2-5 genotypes). Overall, high risk HPV genotypes were
      detected in 48% of the cervical samples, the most frequent types were 16, 18, 31,
      and 51. The proportion of high risk HPV genotypes increased with more severe
      cytological abnormalities. This study demonstrates that the SPF10 primer set is
      more sensitive than the MY09/11 primer set and that genotyping by LiPA tells us
      if the HPV infection is caused by a high risk type and if the infection is mixed.
      Additionally LiPA provides information about the individual genotype when looking
      for persistence of infection. HPV DNA detection and genotyping is therefore a
      useful tool in the colposcopy clinic, used in conjunction with cytology.

PMID- 11992587
TI  - Characterization of Norwalk-like virus associated with gastroenteritis in
      Indonesia.
AB  - Norwalk Virus and Norwalk-like viruses (NLVs) are reportedly responsible for 2.5
      4.0% of nonbacterial acute gastroenteritis (NBAG) worldwide. To help clarify the
      impact of NLVs on NBAG in Indonesia, stool specimens from 102 patients, 74 with
      NBAG and 28 with BAG, were screened for the presence of NLVs, using a reverse
      transcription-polymerase chain reaction (RT-PCR) assay. The specimens were
      subtyped using prototype-specific oligonucleotide probes and were sequenced and
      compared with published NLV sequences. Of the 102 specimens examined, 31 (30%)
      were found to be positive for NLVs. Type-specific probe analysis of the RT-PCR
      products indicated that 31 isolates hybridized to UK1 (Taunton agent) and UK3/4
      (Hawaii agent/Snow Mountain agent) prototype strains. The results of this study
      indicate that prototype strains of NV or NLVs co-circulate in Indonesia and
      contribute to the overall level of acute gastroenteritis throughout the region.

PMID- 11992588
TI  - Parvovirus B19 infection in pregnancy: quantitative viral DNA analysis using a
      kinetic fluorescence detection system (TaqMan PCR).
AB  - Human parvovirus B19 infections are common in the general population, and
      infection during pregnancy may cause hydrops fetalis and fetal death. To initiate
      adequate treatment, accurate laboratory diagnosis is essential. The most
      sensitive tests are nested PCR systems, but these assays provide semiquantitative
      results at best. A parvovirus B19 DNA assay was developed based on the real time
      TaqMan PCR. This method was calibrated on the basis of serial plasmid dilutions
      and tested with an international parvovirus B19 standard. The assay was capable
      of quantifying parvovirus B19 DNA from one to about 5 x 10(7) genome equivalents
      per reaction (corresponding to 100 to 5 x 10(9) genome equivalents per ml serum).
      Samples from 51 pregnant women with suspected acute parvovirus B19 infection were
      tested, and positive PCR results were obtained in at least one of the materials
      investigated in 41 cases. The median viral DNA load in maternal blood samples was
      1.3 x 10(4) copies/ml (range 7.2 x 10(2)-2.6 x 10(7)). Maternal virus DNA
      concentration was not associated with the presence of maternal symptoms and/or
      fetal complications. As the stage of infection was not known in the majority of
      cases, our data do not exclude an association between peak levels of parvovirus
      B19 DNA and the development of complications. Maternal sera and corresponding
      fetal material were available for concurrent testing from 15 DNA-positive cases:
      in most fetal samples, viral DNA concentrations were several orders of magnitude
      higher (up to 2.1 x 10(12) copies/ml) compared to the corresponding maternal
      blood samples.

PMID- 11992589
TI  - Parvovirus B19 nonstructural (NS1) protein as a transactivator of interleukin-6
      synthesis: common pathway in inflammatory sequelae of human parvovirus
      infections?
AB  - This review focuses on the role that human parvovirus B19 nonstructural (NS1)
      protein as a transactivator of the proinflammatory cytokine, interleukin-6 (IL
      6), might play in triggering the multiparametric inflammatory outcomes of B19
      infection. Parvovirus B19 is a ubiquitous virus, and it is often expressed during
      conditions of immunodepression including that induced by long-term chemotherapy,
      viral infection (HIV, HTLV-1), or genetic immunodeficiency disorders. Through NS1
      expression, B19 may contribute to the immune dysregulation associated with these
      disorders, or serve as a cofactor in enhancing retroviral replication. Hence, NS1
      transactivation of proinflammatory cytokine promoters such as IL-6 may be pivotal
      in triggering the various inflammatory and autoimmune disorders that have been
      linked to parvovirus B19 infections.

PMID- 11992590
TI  - Diagnosis and quantitative evaluation of parvovirus B19 infections by real-time
      PCR in the clinical laboratory.
AB  - A real-time PCR assay was developed for quantitative detection of B19 DNA in
      clinical serum samples. The assay was carried out using a LightCycler instrument
      and product formation was monitored continuously with the fluorescent double
      stranded DNA binding dye SYBR Green I. With an optimized PCR protocol, this
      system was able to quantitate the target DNA down to 3 x 10(1) genome
      copies/reaction and to detect as few as 3 x 10(0) genome copies/reaction. Real
      time PCR was used to detect B19 DNA in 108 serum samples from patients with a
      clinical suspicion of B19 infection, showing a sensitivity of 92.7% and a
      specificity of 100% when compared with a standardized PCR-ELISA considered as the
      standard. Using the LightCycler assay, the entire procedure of detection and
      quantitation of B19 DNA in clinical serum samples took up to 90 min proving five
      times faster than PCR-ELISA. B19 DNA quantitation in positive samples by real
      time PCR showed a mean of 1.1 x 10(9) B19 DNA copies/ml in samples in the acute
      active phase of B19 infection (DNA+, IgM+, IgG-), 4.3 x 10(6) B19 DNA copies/ml
      in samples in the active phase (DNA+, IgM+, IgG+), 3.7 x 10(5) genome copies/ml
      in samples in the long-lasting active phase (DNA+, IgM-, IgG+) with a
      statistically significant reduction of B19 DNA content between the group of sera
      in the acute active phase and the group of sera in the active phase of B19
      infection. The high levels of sensitivity, specificity, and rapidity provided by
      the LightCycler technology for the detection and quantitation of B19 DNA
      represent a significant improvement for the laboratory diagnosis of B19
      infection.

PMID- 11992591
TI  - Epidemiology of human Sapporo-like caliciviruses in the South West of England:
      molecular characterisation of a genetically distinct isolate.
AB  - Human enteric caliciviruses have been assigned to two distinct genera: the
      Norwalk-like viruses (NLVs) and the Sapporo-like viruses (SLVs). During a 3-year
      surveillance of gastroenteritis in the South West of England during November 1997
      2000, a total of 27 clinical samples containing SLVs were collected. PCR
      amplicons covering a region of the RNA polymerase gene were obtained from 18 of
      the SLV samples. Sequence analysis of the PCR products indicated that the SLV
      isolates could be assigned to one of the two major genetic groups represented by
      Sapporo and London/92 caliciviruses. One of these isolates belonging to the
      London/92 group (Bristol/98) was subjected to a complete genome sequence
      analysis. The full genomic sequence of the Bristol/98 isolate was determined from
      RNA extracted from a single stool sample and consists of 7490 nucleotides,
      excluding the poly(A) tail. The genome is organised into two open reading frames
      (ORFs), similar to that of Manchester SLV although the small ORF overlapping the
      region encoding the capsid protein observed in Manchester SLV is absent in
      Bristol/98 SLV. The polyprotein (ORF1) of Bristol/98 SLV consists of 2,280 amino
      acids and, as observed in all SLVs, the structural protein is encoded in frame
      and contiguous with the 3' terminus of the ORF1. Phylogenetic studies based on
      complete capsid sequences and genome arrangements within the SLVs indicate that
      the human enteric viruses within the "Sapporo-like" virus clade should be divided
      into two distinct genetic groups analogous to the assignment of the Norwalk-like
      viruses.

PMID- 11992592
TI  - Sequence diversity of human caliciviruses recovered from children with diarrhea
      in Mendoza, Argentina, 1995-1998.
AB  - Human caliciviruses were detected by EIA and/or RT-PCR in stool specimens from
      children with diarrhea treated at out- or in-patient facilities between 1995 and
      1998 in Mendoza, Argentina. Mexico virus-like strains detected by primers NV36/51
      were transiently prevalent in 1995/1996. Significantly more human caliciviruses
      were detected when primers were designed from contemporaneously circulating
      strains. Nucleotide sequences of a highly conserved region in the RNA polymerase
      gene of 10 selected human caliciviruses were determined. Eight strains were
      Norwalk-like viruses and two strains were Sapporo-like viruses. Seven of the
      eight Norwalk-like viruses also were positive by the recombinant Mexico virus
      antigen EIA. The seven Mexico virus EIA-positive strains revealed two patterns in
      the RNA polymerase sequences: two strains were closest to Mexico virus and the
      other five strains were closest to Lordsdale virus. One of the five "Lordsdale"
      viruses was found to be a naturally occurring recombinant between the Mexico
      virus and Lordsdale human calicivirus genetic clusters [Jiang et al., (1999b)
      Archives of Virology 144:2377-2387]. The Mexico virus EIA-negative strain had 73
      77% nucleotide identity with the closest related Norwalk-like viruses, indicating
      it might belong to a new genetic cluster of the Norwalk-like virus genus. The two
      Sapporo-like viruses were distinct genetically; one belonged to the Houston/90 or
      Parkville cluster and the other to a new cluster. Some strains appeared to have
      short periods of prevalence and locally adapted primer pairs significantly
      increased detection rates. The finding of high diversity of circulating strains,
      including recombinant strains and strains with previously unrecognized genetic
      identities, highlights a need for studies of human caliciviruses in these
      children and other populations.

PMID- 11992615
TI  - Caspase-8 activation is necessary but not sufficient for tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in the prostatic
      carcinoma cell line LNCaP.
AB  - BACKGROUND: The differential sensitivity of tumor cells to TRAIL-induced
      apoptosis may be mediated by different intracellular inhibitors of apoptosis, and
      only a few reports have described the pathway(s) that are activated in response
      to TRAIL in prostate cells. METHODS: LNCaP was transfected with a dominant
      negative form of FADD (FADD-DN) and cells were selected in the presence of
      hygromycin. Cell viability was estimated by calcein assay. Apoptosis was
      estimated by caspase activation using both fluorogenic substrates and Western
      blot analysis of activated caspases. To detect cytochrome c release, mitochondria
      free cytosol was prepared and Western blot analysis was performed. RESULTS: LNCaP
      is resistant to TRAIL but TRAIL transiently induces DEVDase activity and
      activation of caspase-8; caspase-2, -3, -7, and -9 were not activated.
      Wortmannin, an inhibitor of the PI3K/Akt pathway, converted the phenotype of
      LNCaP from TRAIL-resistant to -sensitive. In the presence of wortmannin TRAIL
      induced activation of caspase-2, -3, -7, -8, and -9, as well as dissipation of
      mitochondrial transmembrane potential and release of cyto-chrome c from
      mitochondria into the cytosol. In addition, combined TRAIL and wortmannin
      treatment resulted in cleavage of several proteins: PARP, Akt, p21/WAF1, and MDM2
      as well as dephosphorylation of Akt. The proteolysis of p21/WAFI and Akt, which
      are known survival factors, presumably amplify the apoptotic cascade in LNCaP.
      Transfection of FADD-DN in LNCaP resulted in inhibition of caspase activation as
      well as in resistance to combined treatment with TRAIL and wortmannin.
      CONCLUSIONS: These results suggest that caspase-8 activation is necessary but not
      sufficient for TRAIL-mediated apoptosis and is presumably blocked downstream of
      caspase-8 by the PI3K/Akt pathway.

PMID- 11992616
TI  - Confirmation of the prostate cancer susceptibility locus HPCX in a set of 104
      German prostate cancer families.
AB  - BACKGROUND: Several prostate cancer (PCa) susceptibility loci have been reported,
      but attempts to confirm them in independent data sets have produced inconsistent
      results. It is not yet clear, how much of this variation is due to differences
      between different populations. HPCX was originally identified in a combined data
      set of PCa families from the USA and Scandinavia. Considerable differences in the
      frequency of linked families were observed in this heterogeneous family sample as
      well as in following studies. METHODS: In order to estimate the significance of
      HPCX in the German population, DNA samples from 104 PCa families were genotyped
      at six polymorphic markers spanning a region of approximately 14 cM on Xq27-28,
      which includes the proposed HPCX candidate locus. RESULTS: In the entire data
      set, a maximum NPL Z score of 1.20 (P = 0.11) at marker DXS984 was observed.
      Statistically significant evidence for linkage was obtained in the subset of 63
      families with early-onset disease (i.e., < or = 65 years) with a maximum NPL Z
      score of 2.32 (P = 0.009) at the same location. CONCLUSION: Our results confirm
      the existence of a prostate cancer susceptibility gene on Xq27-28 also in the
      German population.

PMID- 11992617
TI  - Establishment and characterization of osseous prostate cancer models: intra
      tibial injection of human prostate cancer cells.
AB  - BACKGROUND: To improve the therapy of advanced prostate cancer (CaP), it is
      critical to develop animal models that mimic CaP bone metastases. Unlike the
      human disease, CaP xenograft models rarely metastasize spontaneously to bone from
      the orthotopic site of primary tumor growth. METHODS: Single-cell suspensions of
      LNCaP, PC-3, LuCaP 35, and LuCaP 23.1 CaP cells were injected directly into tibia
      of SCID mice. Immunohistochemistry and bone histomorphometrical analyses were
      performed to characterize these osseous-CaP models. RESULTS: LuCaP 23.1 yields an
      osteoblastic response, LNCaP yields mixed lesions, and LuCaP 35 and PC-3 result
      in osteolytic responses. We have detected osteoprotegerin, RANK ligand,
      parathyroid hormone-related protein, and endothelin-1, proteins associated with
      bone growth and remodeling, in the CaP cells grown in the bone. CONCLUSIONS:
      These animal models can be used to study biological interactions, pathways, and
      potential therapeutic targets, and also to evaluate new agents for treatment and
      prevention of CaP bone metastasis.

PMID- 11992618
TI  - High level of alpha1-acid glycoprotein in human seminal plasma is associated with
      high branching and expression of Lewis(a) groups on its glycans: supporting
      evidence for a prostatic origin.
AB  - BACKGROUND: Changes in concentration of seminal plasma alpha(1)-acid glycoprotein
      (AGP) have been studied in detail before. However, the source of high levels of
      AGP as well as the glycosylation of seminal plasma AGP has not been elucidated
      yet. METHODS: The glycosylation of AGP was studied by crossed affinity
      immunoelectrophoresis using fucose-specific lectins and immunostaining. Glycan
      structure and monosaccharide analyses were performed by high pH anion exchange
      chromatography with pulsed amperometric detection. Fucosyltransferases were
      analyzed for activity and their substrate specificity was determined. RESULTS:
      Two types of fucosylation were detected; Lewis(x) and Lewis(a). Lewis(a) groups
      were only present on AGP of individuals with a high concentration and were
      completely absent when the AGP concentration in seminal plasma was low. Lewis(a)
      expression coincides with a higher degree of branching of the glycans and a
      relative increased alpha4-fucosyltransferase activity. The molecular weight of
      all seminal plasma AGP was slightly higher than of blood plasma AGP (approx. 47
      vs. 41-43 kDa). CONCLUSIONS: The results indicate that AGP in seminal fluid most
      likely originates from the prostate and that it is either alpha3- or alpha4
      fucosylated.

PMID- 11992619
TI  - Increased expression of lymphocyte-derived cytokines in benign hyperplastic
      prostate tissue, identification of the producing cell types, and effect of
      differentially expressed cytokines on stromal cell proliferation.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) frequently exhibit infiltration of
      CD4 (+)/CD45RO (+) memory-T-lymphocytes. Expression and impact of lymphocyte
      derived growth factors on prostatic stromal cell (PSC) growth were investigated.
      METHODS; Lymphokine synthesis in normal prostate tissues (n = 3), BPH-tissues (n
      = 13), BPH-derived T-cells (n = 6), BPH-derived epithelial cells (BPH-EC) (n =
      5), normal prostate-derived (n = 3) and BPH-derived stromal cell lines (BPH-SC)
      (n = 6), and prostate cancer (CaP) lines (n = 3) was analyzed by RT-PCR and
      Southern-blotting. The effect of interleukin (IL)-2, -4, -7, and interferon-gamma
      (IFN-gamma) on normal and BPH-SC growth was investigated by (3)H-thymidine
      incorporation assays. RESULTS: All BPH-tissues and, to a lesser degree, normal
      prostates, expressed significant amounts of IFN-gamma mRNA. However, only BPH
      tissues contained IL-2 and IL-4 mRNA (ratio: 10:13). BPH-T-cell lines were
      heterogeneous in composition and expressed significant amounts of IFN-gamma, IL
      2, and IL-4 mRNA. Low level expression of these lymphokines was also observed in
      BPH-EC, CaP lines, and PSC lines. IL-2, -7 and IFN-gamma stimulated the
      proliferation of BPH-PSC lines but not that of normal PSC, while IL-4 inhibited
      BPH-PSC growth. CONCLUSIONS: Chronic inflammation may induce an increased growth
      pattern of fibromuscular tissue in BPH similar to that of wound healing.

PMID- 11992620
TI  - Multiple responses to EGF receptor activation and their abrogation by a specific
      EGF receptor tyrosine kinase inhibitor.
AB  - BACKGROUND: Epidermal growth factor receptor (EGF-R) autophosphorylation is
      essential for its intracellular mitogenic signaling via the MAPK pathway and for
      interaction in other cellular processes. Inhibition of this activity in tumor
      cells that predominantly utilise EGF-R therefore offers an alternative approach
      to therapy. METHODS: The ability of a specific inhibitor of EGF-R tyrosine
      kinase, ZM 252868, (TKI) to alter various parameters related to growth in DU145
      and PC3 cell lines was investigated, by immunocytochemistry, Northern blotting,
      Western blotting and invasion assays. RESULTS: In DU145 cultures, the total cell
      population and number of cells in cell cycle decreased in the presence of TKI
      whilst the apoptotic rate was significantly increased. Reduction in
      autophosphorylation of the EGF-R, membrane expression of EGF-R, activation of the
      MAPK, p38, and JNK enzymes and the invasive capacity of DU145 cells was observed
      in the TKI treated cells. Under the same conditions, PC3 cell growth and EGF-R
      expression and MAPK activation were not affected. The use of inhibitors of
      intracellular signaling indicated that the DU145 cells, in contrast to PC3 cells,
      predominantly utilize EGF-R activation of the MAPK signaling pathway for growth.
      CONCLUSIONS: In prostatic cancer patients, in whom androgen resistance has
      developed and whose tumors have upregulated EGF-R for growth, specific TKI's may
      offer an important therapy option.

PMID- 11992621
TI  - Expression of estrogen receptor beta in the fetal, neonatal, and prepubertal
      human prostate.
AB  - BACKGROUND: Although androgens have long been implicated in the development,
      regulation, and pathophysiology of the prostate, evidence suggests that estrogens
      may also affect these processes. Specifically, estrogens have been shown to
      influence the development of the fetal and neonatal rodent prostate and to induce
      a pathognomonic change, termed squamous metaplasia, in the developing and adult
      prostate. Studies have been inconclusive, however, as to whether estrogens
      enhance or restrain the growth of the gland. Although the fetal rodent prostate
      has been reported to contain both estrogen receptor alpha (ER-alpha) and beta (ER
      beta), there have been no reports as to whether either of the ER subtypes is
      expressed in the developing human prostate. METHODS: In the present study, we
      used a novel antibody, directed against a unique sequence in the F domain of ER
      beta, and laser capture microdissection/reverse transcriptase-polymerase chain
      reaction to study the expression of the receptor in the fetal, neonatal, and
      prepubertal human prostate. Results were compared with the expression of ER
      alpha, androgen receptor (AR), prostatic acid phosphatase (PAP), prostate
      specific antigen (PSA), high molecular weight cytokeratin (HMCK), and the
      proliferative marker Ki67. RESULTS: For the first time, we report that ER-beta is
      the only estrogen receptor detected at the protein level in the morphologically
      normal developing human fetal prostate. By midgestation, strong immunostaining
      for ER-beta was detected in the nuclei of nearly 100% of epithelial and in the
      majority of stromal cells. This pattern of expression was evident in the fetal,
      neonatal, and early prepubertal prostate. However, by 11 years postnatal,
      staining for the receptor became restricted primarily to the basal epithelial and
      stromal compartments, a pattern analogous to that observed in the normal adult
      gland. ER-alpha mRNA was present in microdissected stroma of the fetal gland.
      Although ER-alpha was not immunodetected in any morphologically normal fetal
      epithelial or stromal cells, weak staining for the receptor, however, was found
      in some examples of squamous metaplasia, suggesting the role of alpha-subtype in
      this lesion. ER-alpha was clearly visualized immunohistochemically at 1 month of
      postnatal development where it was then localized exclusively in periacinar
      stromal nuclei, which suggests that it may exert paracrine influences on further
      prostatic glandular development. Interestingly, the expression of ER-beta early
      in prostatic development occurred coincident with both the increasing rate of
      epithelial cell proliferation, observed in the first half of gestation, and the
      reported high levels of estrogen in the gland from midgestation until term.
      Paradoxically, however, staining for the receptor remained intense, despite the
      dramatic decrease in Ki67 labeling observed in the second half of gestation.
      CONCLUSION: Our results indicate that the effects of estrogens on the growth of
      the human fetal prostate are mediated primarily by ER-beta but that ER-alpha
      contributes to postnatal glandular development. Furthermore, these results
      suggest that ER-beta, possibly in concert with androgens, may mediate diverse
      effects on prostate epithelial proliferation by first promoting cell expansion
      early in gestation, and then acting to limit growth later in prostatic
      development.

PMID- 11992623
TI  - Alzheimer's disease and oxygen radicals: new insights.
AB  - Alzheimer's disease (AD) is the most common form of neurodegenerative disease,
      with dementia, in the elderly. In addition to the presence of senile plaques and
      neurofibrillary tangles, the AD brain exhibits evidence for oxygen radical
      mediated damage, a situation commonly known as oxidative stress. However, the
      ability to directly implicate this mechanism in AD has been a difficult task for
      several reasons. First, most of the analytical approaches used to investigate
      oxidative stress turned out to be unreliable. Second, the majority of the
      published studies have been performed in post-mortem tissues with advanced
      disease, leaving open the question as to whether oxidative stress is an early
      event or a common final step secondary to the degenerative process. The discovery
      of the isoprostanes, recent studies performed in living patients, and the
      development of transgenic animal models of AD-amyloidosis are three important
      factors that are helping us to better understand and define the role that oxygen
      radicals might play in AD pathogenesis. Here we review some of the most recent
      works that have supported the importance of oxygen radical-mediated damage in AD.
      The accumulated information points toward an earlier involvement than previously
      thought of oxidative stress in the pathogenesis of the disease, making this a
      potential target for therapeutic intervention, especially in subjects at high
      risk for developing AD.

PMID- 11992622
TI  - DNA methylation in the androgen receptor gene promoter region in rat prostate
      cancers.
AB  - BACKGROUND: Invasive adenocarcinomas developing in the rat dorsolateral prostate
      on combined treatment with 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone
      propionate (TP) are biologically androgen-independent and lacking androgen
      receptor protein (AR) expression. The present study was conducted to assess the
      mechanisms underlying this loss of AR expression in rat prostate cancer. METHODS:
      The methylation status of the AR gene promoter region in rat prostate cancer and
      cell lines (PLS10, 20, and 30) was examined by Southern blotting, methylation
      specific polymerase chain reaction, and methylation-sensitive single-strand
      conformation analysis (MS-SSCA). RESULTS: AR mRNA expression was not detected in
      any of the rat prostate cancers or cancer cell lines tested by Northern blot
      analysis. Higher levels of methylated CpGs were observed in PLS20 than PLS10 or
      30. Demethylation treatment by 5-aza-2'-deoxycytidine restored AR mRNA expression
      in PLS20. The CpGs suggested to be responsible for AR expression in rat prostate
      cancer were found to be located -9 and -1 nucleotides upstream of the
      transcriptional initiation site. All of the examined rat prostate and seminal
      vesicle cancers demonstrated hypermethylation at these CpG sites. CONCLUSIONS:
      These data clearly demonstrate that aberrant hypermethylation in the AR promoter
      region may play a critical role in AR expression in rat prostate cancers.

PMID- 11992624
TI  - Hydrogen peroxide-induced current in Xenopus oocytes: current characteristics
      similar to those induced by the removal of extracellular calcium.
AB  - The effects of hydrogen peroxide (H(2)O(2)) exposure on Xenopus oocytes were
      examined. An application of 1 microL of 10% H(2)O(2) to oocytes voltage-clamped
      in 1mL of Modified Barth Saline (MBS: final concentration of 0.01% H(2)O(2))
      induced a transient ionic current. This H(2)O(2)-induced current, however, was
      not transient but long-lasting in a Ca(2+)-free medium. The H(2)O(2)-induced
      current was independent of increases in intracellular calcium. Intriguingly, the
      H(2)O(2)-induced current was similar in signature to one stimulated by the
      removal of extracellular calcium (Ca(o)(2+)-inactivated current). Both currents
      (a) were inactivated by 1.5mM LaCl(3), GdCl(3), CdCl(2), NiCl(2), CaCl(2), or
      MgCl(2), but not by LiCl or KCl, (b) exhibited reversal potential shifts to more
      positive values with increasing external NaCl, (c) showed linear voltage-current
      (I-V) relationships, and (d) were reversibly inhibited by two chloride channel
      blockers, 200 microM 5-nitro-2-(3-phenylpropylamino)-benzoic acid and 250 microM
      niflumic acid. Additionally, H(2)O(2) was still able to induce current in oocytes
      loaded with either catalase or N-acetyl-L-cysteine, H(2)O(2) scavengers. These
      results imply that H(2)O(2) induces this ionic current possibly through the
      activation of Ca(o)(2+)-inactivated channels by an extracellular mechanism.

PMID- 11992625
TI  - Inhibition of superoxide anion generation by YC-1 in rat neutrophils through
      cyclic GMP-dependent and -independent mechanisms.
AB  - 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a soluble guanylyl
      cyclase (sGC) activator, inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)
      induced superoxide anion (O(2)*(-)) generation and O(2) consumption in rat
      neutrophils (IC(50) values of 12.7+/-3.1 and 17.7+/-6.9 microM, respectively).
      Inhibition of O(2)*(-) generation by YC-1 was partially reversed by the cyclic
      GMP-lowering agent 6-anilinoquinoline-5,8-quinone (LY83583) and by the Rp isomer
      of 8-(4-chlorophenylthio)guanosine-3',5'-monophosphorothioate (Rp-8-pCPT-cGMPS),
      a cyclic GMP-dependent protein kinase inhibitor. In cell-free systems, YC-1
      failed to alter O(2)*(-) generation during dihydroxyfumaric acid autoxidation,
      phorbol 12-myristate 13-acetate (PMA)-activated neutrophil particulate NADPH
      oxidase preparation, and arachidonic acid-induced NADPH oxidase activation. YC-1
      increased cellular cyclic GMP levels through the activation of sGC and the
      inhibition of cyclic GMP-hydrolyzing phosphodiesterase activity. The plateau
      phase, but not the initial spike, of fMLP-induced [Ca(2+)](i) changes was
      inhibited by YC-1 (IC(50) about 15 microM). fMLP- but not PMA-induced
      phospholipase D activation was inhibited by YC-1 (IC(50) about 28 microM).
      Membrane-associated ADP-ribosylation factor and Rho A in cell activation was also
      reduced by YC-1 at a similar concentration range. Neither cytosolic protein
      kinase C (PKC) activity nor PKC membrane translocation was altered by YC-1. YC-1
      did not affect either fMLP-induced phosphatidylinositol 3-kinase activation or
      p38 mitogen-activated protein kinase phosphorylation, but slightly attenuated the
      phosphorylation of extracellular signal-regulated kinase. Collectively, these
      results indicate that the inhibition of the fMLP-induced respiratory burst by YC
      1 is mediated by cyclic GMP-dependent and -independent signaling mechanisms.

PMID- 11992626
TI  - Dual coupling of MT(1) and MT(2) melatonin receptors to cyclic AMP and
      phosphoinositide signal transduction cascades and their regulation following
      melatonin exposure.
AB  - In this investigation, we wanted to determine whether MT(1) or MT(2) melatonin
      receptors are capable of coupling to the phosphoinositide (PI) signal
      transduction cascade. In addition, we wanted to assess the effects of chronic
      melatonin exposure on MT(1) and MT(2) melatonin receptor-mediated stimulation of
      PI hydrolysis. We also assessed the effects of chronic melatonin exposure on
      other parameters of the MT(2) melatonin receptor function including total
      specific 2-[125I]-iodomelatonin binding, the affinity of melatonin for the
      receptor, and melatonin (1nM)-mediated inhibition of cyclic 3',5'-adenosine
      monophosphate (cAMP) accumulation. Investigation of the PI signal transduction
      cascade activated by either the MT(1) or MT(2) melatonin receptor expressed in
      Chinese hamster ovary (CHO) cells showed that melatonin (1pM to 1mM) was able to
      stimulate the formation of PIs to approximately 40-60% over basal [EC(50):
      MT(1)=29nM (2-300nM) and MT(2)=1.1nM (0.32-3.5nM), N=5]. This response was
      mediated via receptors based upon the findings that melatonin did not stimulate
      the formation of PIs in CHO cells devoid of receptor and that antagonism of MT(2)
      melatonin receptors by 4P-PDOT (AH 024; 4-phenyl-2-propionamidotetralin)
      attenuated melatonin-mediated stimulation of PI hydrolysis in CHO cells
      expressing the MT(2) melatonin receptor. The consequence of chronic melatonin
      exposure on MT(1) and MT(2) receptor function was also examined. Pretreatment of
      either MT(1)- or MT(2)-CHO cells with melatonin (1 microM for 5hr) resulted in:
      (a) a complete loss of melatonin-mediated stimulation of PI hydrolysis, and (b)
      an attenuation of melatonin (1nM)-mediated inhibition of forskolin-induced cAMP
      accumulation by approximately 20-40%. The desensitization of the PI hydrolysis
      signal transduction cascades coupled to either MT(1) or MT(2) melatonin receptors
      following chronic melatonin exposure was not due to depleted phospholipid pools,
      to elevated basal levels, or to decreases in receptor affinity and density. This
      dual coupling of melatonin receptors to different signal transduction cascades
      may contribute to the diversity of melatonin receptor function in vivo.

PMID- 11992627
TI  - Involvement of the muscarinic acetylcholine receptor in inhibition of cell
      migration.
AB  - Activation of G protein-coupled receptors is known to stimulate cell migration,
      but receptor-mediated signals inhibiting cell migration have not been identified.
      We investigated the ability of transfected human M(3) muscarinic acetylcholine
      receptors (mAChR) to regulate the migration of Chinese hamster ovary (CHO) cells.
      Single cells migrated on colloidal gold applied to fibronectin-coated plates, and
      videomicroscopy was used to measure cell spreading and migration. Activation of
      M(3) mAChR with the agonist carbachol was found to inhibit cell migration,
      whereas direct activation of protein kinase C (PKC) with PMA was found to
      stimulate migration. The amount of cell adhesion and spreading was found to be
      equivalent for carbachol- and PMA-treated cells. Selective inactivation of
      conventional PKC isoforms with Go6976 (C(24)H(18)N(4)O) abolished the PMA
      mediated increase in cell migration. In contrast, the mAChR-mediated decrease in
      migration was not altered by Go6976, but was abolished when both novel and
      conventional PKC isoforms were inactivated by calphostin C or chelerythrine.
      These findings suggest involvement of conventional PKC isoforms in the
      stimulation of migration and of novel PKC isoforms in the inhibition of
      migration. Carbachol- but not PMA-treated cells exhibited an elongated morphology
      reminiscent of migrating cells that cannot detach their trailing edges from the
      substratum. Similarly, carbachol-treated cells detached less readily from
      fibronectin than control or PMA-treated cells when integrin activity was
      diminished by the chelation of Ca(2+) and Mg(2+). Finally, the carbachol-induced
      diminution of cell detachment was preserved after inhibition of the conventional
      PKC isoforms with Go6976, but was abrogated by treatment with either calphostin C
      or chelerythrine. These findings suggest that mAChR activation diminishes the
      ability of cells to detach from the substratum, resulting in diminished
      migration. This is in contrast to the direct activation of PKC with PMA, which
      stimulates migration.

PMID- 11992628
TI  - Enhanced clearance of topoisomerase I inhibitors from human colon cancer cells by
      glucuronidation.
AB  - As part of a program to identify novel mechanisms of resistance to topoisomerase
      I (topo I) inhibitors, the cellular pharmacology of 7-ethyl-10
      hydroxycamptothecin (SN-38), the active metabolite of clinically used irinotecan
      (CPT-11) and NU/ICRF 505, an anthraquinone-tyrosine conjugate, has been
      investigated in two human colorectal cancer (CRC) cell lines. Two novel
      metabolites of NU/ICRF 505 (M1 and M2) and a single metabolite of SN-38 (M1) were
      detected by high performance liquid chromatography in the culture medium of HT29
      cells but were absent in HCT116 cells. Identities of all three metabolites were
      established by a combination of biochemical and physicochemical techniques. M1 of
      SN-38 was the C10-(beta)-glucuronide of the parent lactone while M1 of NU/ICRF
      505 was the C4-O-glucuronide and M2 the tyrosine-O-glucuronide, both of the
      parent compound. Drug transport studies revealed that by 24hr HT29 cells had
      effectively cleared 82.5% of NU/ICRF 505 (10 microM) into the culture medium as
      the two glucuronides. In contrast, intracellular concentrations of NU/ICRF 505
      were maintained in HCT116 cells in the absence of glucuronidation at a level 550
      times greater than in HT29 cells. HT29 cells cleared 40.9% of SN-38 (1 microM) as
      the glucuronide to the culture medium, while the parent drug was maintained at a
      level 2-fold greater in HCT116 cells. Enhanced drug clearance due to
      glucuronidation may contribute to intrinsic drug resistance of human CRC.

PMID- 11992629
TI  - Bilirubin and uroporphyrinogen oxidation by induced cytochrome P4501A and
      cytochrome P4502B. Role of polyhalogenated biphenyls of different configuration.
AB  - In previous work it was shown that hepatic microsomes from rats treated with 3
      methylcholanthrene and similar inducers had increased bilirubin-degrading
      activity. The activity was further stimulated by addition of 3,4
      tetrachlorobiphenyl (TCB), a response specifically dependent on CYP1A1. Here, we
      compared the effect of adding PCBs of either planar or non-planar configuration
      on rate of bilirubin degradation, monooxygenase activity and NADPH/O(2)
      consumption by liver microsomes from animals treated with either phenobarbital or
      3-methylcholanthrene/beta-naphthoflavone. We also examined the oxidation of
      uroporphyrinogen (hexahydro-uroporphyrin) (URO'gen) under these conditions.
      Polychlorinated biphenyl (PCBs) stimulated the rate of bilirubin and URO'gen
      oxidation with microsomes expressing high levels of either CYP2B or CYP1A,
      inhibiting at the same time their monooxygenase activities (PROD and EROD,
      respectively); however, non-planar di-ortho-substituted PCBs were preferentially
      active with phenobarbitone-induced microsomes, in contrast to those active with 3
      methylcholanthrene/beta-naphthoflavone microsomes, where a planar configuration
      was required for activity. An antibody raised against CYP2B1 markedly inhibited
      the PCB-dependent bilirubin degradation and PROD activities of phenobarbital
      induced microsomes with similar dose-response curves for the two effects.
      Increased microsomal utilizations of NADPH and O(2) were also caused by PCBs with
      both types of induced microsomes and here again PCBs of different configuration
      were preferentially active. It is concluded that PCBs of the appropriate
      configuration may interact with either CYP1A1 or CYP2B1, increase production of
      oxidative species by an uncoupling mechanism, and lead to oxidation of target
      molecules in the cell, among these uroporphyrinogen and bilirubin.

PMID- 11992630
TI  - The modulation of the DNA-damaging effect of polycyclic aromatic agents by
      xanthines. Part I. Reduction of cytostatic effects of quinacrine mustard by
      caffeine.
AB  - Recently, accumulated statistical data indicate the protective effect of caffeine
      consumption against several types of cancer diseases. There are also reports
      about protective effect of caffeine and other xanthines against tumors induced by
      polycyclic aromatic hydrocarbons. One of the explanations is based on biological
      activation of such carcinogens by cytochromes that are also known for metabolism
      of caffeine. However, there is also numerous data indicating reverse effect on
      cytotoxicity of anticancer drugs that inhibit the action of topoisomerase I (e.g.
      Camptothecin or Topotecan) and topoisomerase II inhibitors (e.g. Doxorubicin,
      Mitoxantrone or mAMSA). In this work we tested the hypothesis that the caffeine
      protective effect is the result of sequestering of aromatic mutagens by formation
      of stacking (pi-pi) complexes. As the models for the study we have chosen two
      well-known mutagens, that do not require metabolical activation: quinacrine
      mustard(QM, aromatic, heterocyclic nitrogen mustard) and mechlorethamine (NM2,
      aliphatic nitrogen mustard). The flow cytometry study of these agents' action on
      the cell cycle of HL-60 cells indicated that caffeine prevents the cytotoxic
      action of QM, but not that of NM2. The formations of stacking complexes of QM
      with caffeine were confirmed by light absorption, calorimetric measurements and
      by molecular modeling calculation. Using the statistical thermodynamics
      calculations we calculated the "neighborhood" association constant (K(AC)=59+/
      2M(-1)) and enthalpy change (DeltaH(0')=-116cal mol(-1)); the favorable entropy
      change of complex formation (DeltaS(0')=7.72cal mol(-1)K(-1), due to release of
      several water molecules, associated with components in the process of complex
      formation). The Gibbs' free energy change of QM-CAF formation is DeltaG(0')=
      2.41kcal mol(-1). We were unable to detect any interaction between NM2 and
      caffeine either by spectroscopic or calorimetric measurement. In order to
      establish, whether the intercalation of QM plays any role in cytotoxic effect we
      tested, as a control, non-alkylatiatig, but also intercalating QM derivative
      quinacrine (Q). The later had no cytostatic effect on HL-60 cell even at there
      order of higher concentration than QM or NM2 but, similar to QM forms (which we
      demonstrated) stacking complexes with caffeine (K(AC)=75+/-3M(-1)). These results
      strongly indicate, that the attenuating effect of caffeine on cytotoxic or
      mutagenic effects of some mutagens, is not the results of metabolic processes in
      the cells, but simply the physicochemical process of sequestering of aromatic
      molecules (potential carcinogens or mutagens) by formation of stacking complexes
      with them. The caffeine may then act as the "interceptor" of potential
      carcinogens (especially in the upper part of digesting track where its
      concentration can reach the concentration of mM level). There is, however, no
      indication either in the literature or in our experiments that xanthines can
      reverse the damage to nucleic acids when the damage to DNA has already occurred.

PMID- 11992631
TI  - The modulation by xanthines of the DNA-damaging effect of polycyclic aromatic
      agents. Part II. The stacking complexes of caffeine with doxorubicin and
      mitoxantrone.
AB  - Recently accumulated statistical data indicate the protective effect of caffeine
      consumption against several types of cancer diseases. There are also reports
      about protective effect of caffeine and other xanthines against tumors induced by
      polycyclic aromatic hydrocarbons. One of the explanations of this phenomenon is
      based on biological activation of such carcinogens by cytochromes that are also
      known for metabolism of caffeine. In the accompanying paper [Kapuscinski et al.,
      this issue] we provide evidence (flow cytometry and the cell cycle analysis) that
      the cytostatic effects of caffeine (CAF) on two DNA alkylating agents, which do
      not require the biological activation, depend on their ability to form stacking
      (pi-pi) complexes. In this study, we use physicochemical techniques (computer
      aided light absorption and microcalorimetry), and molecular modeling to examine
      previously published qualitative data. This is published both by our and other
      group's data, indicates that CAF is able to modify the cytotoxic and/or
      cytostatic action of the two well known antitumor drugs doxorubicin (DOX) and
      mitoxantrone (MIT). To obtain the quantitative results from the experimental data
      we used the statistical-thermodynamical model of mixed aggregation, to find the
      association constants K(AC) of the CAF-drug interaction (128+/-10 and 356+/-21M(
      1) for DOX-CAF and MIT-CAF complex formation, respectively). In addition, the
      favorable enthalpy change of CAF-MIT (DeltaH=-11.3kcal/mol) was measured by
      microcalorimetry titration. The molecular modeling (semi-empirical and force
      field method) allowed us to obtain the geometry of these complexes, which
      indicated the favorable energy (DeltaE) of complex formation of the protonated
      drug's molecules in aqueous environment (-7.4 and -8.7kcal/mol for DOX-CAF.5H(2)O
      and MIT-CAF.8H(2)O complex, respectively). The molecular modeling calculation
      indicates the existence of CAF-drug complexes in which the MIT molecules are
      intercalated between two CAF molecules (DeltaE=-29.9kcal/mol). These results
      indicate that the attenuating effect of caffeine on cytotoxic or mutagenic
      effects of some polycyclic aromatic mutagens cannot be the result of metabolic
      activation in the cells, but simply is the physicochemical process of the
      sequestering of aromatic molecules (e.g. carcinogens or mutagens) by formation of
      the stacking complexes. The caffeine may then act as the "interceptor" of
      potential carcinogens (especially in the upper part of digesting track) where its
      concentration can reach the mM level). There is, however, no indication, both, in
      the literature or from our experiments, that the xanthines can reverse the damage
      to nucleic acids at the point when the damage to DNA has already occurred.

PMID- 11992632
TI  - Alterations in cellular Ca(2+) and free iron pool by sulfur amino acid
      deprivation: the role of ferritin light chain down-regulation in prooxidant
      production.
AB  - Deficiency of sulfur amino acids occurs in certain pathophysiological states such
      as protein-calorie malnutrition. Sulfur amino acid deprivation (SAAD) increases
      oxidative stress through a decrease in GSH. Ferritin expression is induced by
      oxidative stress, which confers resistance to oxidative insults. The effects of
      SAAD on the changes in cellular Ca(2+) and free iron pool, prooxidant production
      and the ferritin light chain (FLC) expression were comparatively evaluated in
      Hepa1c1c7 and Raw264.7 cells. [Ca(2+)](i) was rapidly increased by SAAD.
      Sulfhydryl-containing compounds prevented the increase in [Ca(2+)](i) in cells
      under SAAD, supporting the role of redox-state in the regulation of [Ca(2+)](i).
      Thapsigargin or Ca(2+)-free medium inhibited the increase in [Ca(2+)](i), showing
      that Ca(2+) originated from endoplasmic reticulum as well as from extracellular
      source. Inhibition of Ca(2+) mobilization decreased the fluorescence of Phen
      Green SK inside cells, representing the inhibition of free iron release. Both
      inhibition of Ca(2+) mobilization and iron chelation decreased
      dichlorofluorescein oxidation, indicating the possibility that the increase in
      [Ca(2+)](i) affected that in cellular free iron and prooxidant production. FLC
      protein level was immunochemically detectable in Raw264.7 cells, but not in
      Hepa1c1c7 cells. SAAD alone (or in combination with FeSO(4)) down-regulated FLC
      protein expression, while SAAD increased the FLC mRNA level in both Hepa1c1c7 and
      Raw264.7 cells. Calcium or iron chelators prevented increases in the FLC mRNA.
      These results provided evidence that changes in cellular Ca(2+) and iron pool by
      SAAD increased cellular oxidative stress and that the down-regulation of FLC
      protein by SAAD would further enhance prooxidant production in spite of the
      increase in FLC mRNA.

PMID- 11992633
TI  - 7-Benzylamino-6-chloro-2-piperazino-4-pyrrolidino-pteridine, a potent inhibitor
      of cAMP-specific phosphodiesterase, enhancing nuclear protein binding to the CRE
      consensus sequence in human tumour cells.
AB  - The cAMP-specific phosphodiesterase isoenzyme family PDE4 represents the highest
      cAMP-hydrolysing activity in many human cancer cell lines including the human
      large cell lung carcinoma cell line LXFL529L. Treatment of LXFL529L cells with
      the potent PDE4 inhibitor 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidino
      pteridine (DC-TA-46) induces dose-dependent growth inhibition. Cells are arrested
      in the G(1)-phase of the cell cycle and the induction of apoptosis is observed.
      In this study, we investigated the effect of DC-TA-46 on downstream elements of
      the cAMP-pathway. DC-TA-46 mediated inhibition of PDE4 activity in LXFL529L cells
      resulted in an increase of the intracellular cAMP level and significant induction
      of the activity of protein kinase A (PKA). The regulatory PKA subunit RIalpha was
      predominantly expressed in LXFL529L cells. In contrast to effects induced by cAMP
      analogues like 8-Cl-cAMP, the expression of the regulatory subunits of PKA
      remained unaffected by DC-TA-46. Treatment of LXFL529L cells with DC-TA-46
      enhanced the binding of nuclear proteins to the cAMP-responsive element (CRE)
      consensus sequence TGACGTCA in a time- and dose-dependent manner, indicating the
      activation of transcription factors by PKA phosphorylation.

PMID- 11992634
TI  - Intracellular localization of 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidino
      pteridine in membrane structures impeding the inhibition of cytosolic cyclic AMP
      specific phosphodiesterase.
AB  - 7-Benzylamino-6-chloro-2-piperazino-4-pyrrolidino-pteridine (DC-TA-46) is a
      potent inhibitor of the rolipram-sensitive cAMP-specific phosphodiesterase
      isoenzyme family PDE4. DC-TA-46 inhibits cAMP-hydrolysis of PDE4 isolated from
      solid tumors of the human large cell lung tumor xenograft LXFL529 in the
      nanomolar range (IC(50)=16+/-5nM). Tumor cells, however, are growth inhibited
      only in the lower micromolar range as shown for the human large cell lung
      carcinoma cell line LXFL529L. To investigate reasons for the discrepancy between
      IC(50) values for target inhibition and inhibition of cell growth, uptake,
      subcellular distribution and elimination of the compound were measured. DC-TA-46
      was rapidly taken up by the cells, predominantly localized in intracellular
      membranes. Elimination was slow, with 70% of the compound still persisting in the
      membranes 50hr after withdrawal. Confocal laser scanning microscopy showed a
      clear colocalization with a fluorescent marker for the endoplasmatic reticulum
      (ER). As a result of the subcellular localization, the membrane-bound PDE
      activity of LXFL529L cells was effectively inhibited by DC-TA-46 (IC(50)=0.06+/
      0.02 microM). In contrast, inhibition of the cytosolic PDE activity was only
      achieved at concentrations >1 microM (IC(50)=2.0+/-0.5 microM), in the
      concentration range where also growth inhibition was observed. Thus, the
      inhibition of the intracellular PDE activity in the different cellular
      compartments appears to represent an important parameter for the evaluation of
      the inhibitory properties at least of this class of compounds.

PMID- 11992635
TI  - Monoamine neurotoxins-induced apoptosis in lymphocytes by a common oxidative
      stress mechanism: involvement of hydrogen peroxide (H(2)O(2)), caspase-3, and
      nuclear factor kappa-B (NF-kappaB), p53, c-Jun transcription factors.
AB  - The destruction of dopaminergic and serotonergic nerve cells by selective 6
      hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) and 5,7
      dihydroxytryptamine (5,7-DHT), respectively, is a commonly used tool to
      investigate the mapping of neuronal pathways, elucidation of function and to
      mimic human neurodegenerative disease such as Parkinson's and Alzheimer's
      diseases. Despite intense investigations, a complete picture of the precise
      molecular cascade leading to cell death in a single cellular model is still
      lacking. In this study, we provide evidence that 6-OHDA, 5,6- and 5,7-DHT toxins
      induced apoptosis in peripheral blood lymphocytes cells in a concentration
      dependent fashion by a common oxidative mechanism involving: (1) the oxidation of
      toxins into quinones and production of the by-product hydrogen peroxide,
      reflected by desipramine-a monoamine uptake blocker-and antioxidants inhibition,
      (2) activation and/or translocation of nuclear factor-kappaB, p53 and c-Jun
      transcription factors, showed by immunocytochemical diaminobenzidine-positive
      stained nuclei, (3) caspase-3 activation, reflected by caspase Ac-DEVD-CHO
      inhibition, (4) mRNA and protein synthesis de novo according to cycloheximide and
      actinomycin D cell death inhibition. These results are consistent with the notion
      that uptake and intracellular autoxidation of those toxins precede the apoptotic
      process and that once H(2)O(2) is generated, it is able to trigger a specific
      cell death signalisation. Thus, taken together these results, we present an
      ordered cascade of the major molecular events leading peripheral blood
      lymphocytes to apoptosis. These results may contribute to explain the importance
      of H(2)O(2) as a second messenger of death signal in some degenerative diseases
      linked to oxidative stress stimuli.

PMID- 11992636
TI  - Mechanisms of apoptosis by the tyrphostin AG957 in hematopoietic cells.
AB  - AG957 (NSC 654705) is a tyrphostin tyrosine kinase inhibitor that has been
      demonstrated previously to induce growth arrest in chronic myelogenous leukemia
      cells by inhibiting p210(bcr-abl) kinase activity and by stabilizing the
      association of p210(bcr-abl) kinase with its signaling adaptor molecules, Shc and
      Grb2. In previous studies, it has been demonstrated that AG957-associated down
      regulation of bcr-abl activates the cytochrome c/Apaf-1/caspase-9 pathway and
      induces apoptosis in chronic myelogenous leukemia blasts and progenitor cells.
      While AG957 has been purported to have specificity for the p210(bcr-abl) kinase,
      antiproliferative effects of AG957 in normal T-lymphocytes and bcr-abl negative
      leukemia cells suggest that other targets, such as c-CBL, may be substrates. In
      this study, we explored the mechanisms of AG957-mediated growth inhibition and
      apoptosis in the p210(bcr-abl) negative leukemia cell lines Nalm-6 and Jurkat,
      and demonstrate that AG957-mediated apoptosis is associated with altered
      phosphorylation of Akt and BAD, which destabilizes the Bcl-xL/BAD complex and
      releases the block to apoptosis. We, therefore, propose that AG957 induces
      apoptosis in bcr-abl negative hematopoietic cells by affecting the
      phosphorylation state of phosphatidylinositol-3 kinase/Akt.

PMID- 11992637
TI  - Associations between human liver and kidney cadmium content and immunochemically
      detected CYP4A11 apoprotein.
AB  - This present study was undertaken to assess potential effects of cadmium on
      CYP4A11 apoprotein in human liver and kidney as detected by Western blotting
      using a highly specific anti-peptide antibody. Liver and kidney cortex samples
      were autopsy specimens of 37 individuals (26 males and 11 females) whose ages
      ranged from 3 to 89 years. All were Caucasians who had not been exposed to
      cadmium in the workplace. Reduced CYP4A11 apoprotein levels were found in chronic
      hepatitis samples and in liver samples showing fatty changes. In contrast,
      increased CYP4A11 apoprotein levels were found in liver samples having higher
      cadmium content compared to the lower cadmium content samples. Increased CYP4A11
      levels were also found in liver samples from female donors, compared to male
      donors; the difference being attributable to higher female liver cadmium burden.
      In distinction to liver, lowered CYP4A11 levels were seen in the kidney cortex
      samples which have high cadmium content. It is proposed here that the difference
      between the absolute cadmium burden of the liver and kidney samples may be
      responsible for the different patterns of expression of CYP4A11 in these two
      tissues. Further, since cadmium exposure may be associated with derangement in
      blood pressure control, it is interesting to note the possible relationship
      between altered CYP4A11-dependent production of arachidonic acid hydroxy and
      epoxy metabolites in kidney cortex and altered control of blood pressure. Our
      findings provide a possible link between these observations.

PMID- 11992638
TI  - Inhibition of hepatic stellate cell collagen synthesis by N
      (methylamino)isobutyric acid.
AB  - The increased deposition of extracellular matrix by hepatic stellate cells
      following liver injury, in a process known as activation, is considered a key
      mechanism for increased collagen content of liver during the development of liver
      fibrosis. We report that N-(methylamino)isobutyric acid (MeAIB), a specific
      inhibitor of System A-mediated amino acid uptake, reduces the accumulation of
      collagen in CFSC-2G hepatic stellate cell cultures and in a rat model of liver
      injury and fibrosis. Rat CFSC-2G cells were cultured in 0-5mM MeAIB, and the
      accumulation and synthesis of collagen were measured by binding to Sirius red F3B
      and pulse-labeling with [3H]-proline, respectively. The effect of MeAIB on
      collagen accumulation in vivo was evaluated utilizing a rat model of hepatic
      fibrosis. MeAIB inhibited collagen accumulation in CFSC-2G cultures in a
      concentration-dependent manner with 5mM MeAIB reducing collagen 44.6+/-1.2%
      compared with the control. In CFSC-2G cultures, MeAIB selectively inhibited the
      incorporation of proline into cellular macromolecules by 43+/-4%, while the
      synthesis of proteins containing leucine was not affected. In vivo, oral
      administration of 160mg MeAIB/kg body weight per day to rats significantly
      reduced the hepatic collagen accumulation in response to 1 week of CCl(4)-induced
      liver injury. MeAIB reduces the accumulation of collagen in CFSC-2G hepatic
      stellate cell cultures and in a CCl(4)-induced rat model of liver injury and
      fibrosis.

PMID- 11992639
TI  - Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide,
      at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10.
AB  - Vitilevuamide, a bicyclic 13 amino acid peptide, was isolated from two marine
      ascidians, Didemnum cuculiferum and Polysyncranton lithostrotum. Vitilevuamide
      was cytotoxic in several human tumor cell lines, with LC(50) values ranging from
      6 to 311nM, and analysis in a 25-cell line panel revealed a weak correlation with
      several taxol analogs. Vitilevuamide was strongly positive in a cell-based screen
      for inhibitors of tubulin polymerization. Vitilevuamide at 9 microg/mL (5.6
      microM) had an effect equivalent to the maximal effect of colchicine at 25
      microg/mL (62.5 microM). Vitilevuamide was active in vivo against P388
      lymphocytic leukemia, increasing the lifespan of leukemic mice 70% at 30
      microg/kg. We hypothesized that at least part of the cytotoxic mechanism of
      vitilevuamide was due to its inhibition of tubulin polymerization. Vitilevuamide
      was found to inhibit polymerization of purified tubulin in vitro, with an IC(50)
      value of approximately 2 microM. Cell cycle analysis showed that vitilevuamide
      arrested cells in the G(2)/M phase with 78% of treated cells tetraploid after
      16hr. Therefore, vitilevuamide was tested for its ability to inhibit binding of
      known tubulin ligands. Vitilevuamide exhibited non-competitive inhibition of
      vinblastine binding to tubulin. Colchicine binding to tubulin was stabilized in
      the presence of vitilevuamide in a fashion similar to vinblastine. Dolastatin 10
      binding was unaffected by vitilevuamide at low concentrations, but inhibited at
      higher ones. GTP binding was also found to be weakly affected by the presence of
      vitilevuamide. These results suggest the possibility that vitilevuamide inhibits
      tubulin polymerization via an interaction at a unique site.

PMID- 11992640
TI  - Modifications of deoxycytidine kinase and deaminase activities by docosahexaenoic
      acid in normal and transformed rat fibroblasts.
AB  - Deoxycytidine kinase (dCK) and deoxycytidine deaminase (dCDA) are two key enzymes
      in the activation and inactivation, respectively, of deoxycytidine (dCyd) and
      several chemotherapeutically important nucleoside analogues. To investigate
      whether supplementation of docosahexaenoic acid, an n-3 fatty acid found mainly
      in fish oil, can modulate the activity of both enzymes, normal (Rat-2) and
      transformed (NW-16) rat fibroblasts were cultured in medium supplemented with or
      without DHA. DHA supplementation increased the phosphorylation efficiency
      (V(max)/K(m)) of dCK but decreased the deamination efficacy of dCDA in the
      transformed cells as compared with those in the normal fibroblasts. Enzyme
      activity of dCK was decreased by DHA in Rat-2 cells and increased in NW-16 cells.
      In contrast, dCDA activity was elevated in the normal fibroblasts in response to
      DHA. As a result, the activity ratio of dCK/dCDA (a potential indicator of
      chemosensitivity) was decreased in the normal fibroblasts but increased in the
      transformed cells by DHA. We have observed previously that the toxicity of
      nucleoside drugs (particularly arabinosylcytosine) was increased in tumor cells
      and decreased in normal cells in response to DHA and proposed a mechanism of
      changes in drug activation/inactivation. The present data support this hypothesis
      and suggest that DHA has the potential to selectively target chemotherapeutic
      drugs toward tumor cells while at the same time reducing host toxicity.

PMID- 11992641
TI  - Effect of the new matrix metalloproteinase inhibitor RO-28-2653 on mitochondrial
      function.
AB  - Matrix metalloproteinases (MMPs) have recently become interesting as potential
      anticancer drugs. RO-28-2653 is a promising compound because of its
      antimetastatic and antiangiogenic activities. Due to the structural similarity of
      RO-28-2653 to mitochondriotoxic agents, speculation has arisen that this
      substance might impair mitochondrial function. We, therefore, investigated the
      effects of RO-28-2653 on mitochondrial enzymes and on the functional properties
      of isolated mitochondria and skinned muscle fibers from rat hearts. Results were
      compared to the action of amytal and 2,4-dinitrophenol (2,4-DNP), both of which
      are well documented mitochondriotoxic compounds. In contrast to 2,4-DNP, RO-28
      2653 did not uncouple oxidative phosphorylation, although higher concentrations
      of the compound did impair mitochondrial function. Using malate/pyruvate as
      substrate, 50 microM of RO-28-2653 inhibited mitochondrial respiration in
      isolated mitochondria and skinned fibers by 23 and 11%, respectively while 2mM of
      amytal elicited almost complete inhibition of the mitochondrial respiration. RO
      28-2653 (50 micro) inhibited succinate-dependent respiration in both systems by
      43 and 24%, respectively while 2mM of amytal caused 41 and 23% inhibition,
      respectively. There was no change in the ADP/O ratios. RO-28-2653 (50 microM) did
      not significantly alter the activity of the respiratory chain complexes or
      succinate dehydrogenase, although citrate synthase (CS) was inhibited by upto
      71%. This inhibition was non-competitive at a K(i) of 25+/-5 microM. Inhibitory
      effects in the presence of hydrophobic substances, such as BSA and Triton X-100,
      were significantly lower in both test systems. In conclusion, high concentrations
      of RO-28-2653 impair mitochondrial function, although compared to amytal and 2,4
      DNP, this is rather low. The resultant impairment is less pronounced in the more
      complex skinned muscle fiber system, and is dependent on hydrophobic
      interactions.

PMID- 11992642
TI  - Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and
      apoptotic morphology in unselected human ovarian cancer cell lines as a response
      to docetaxel.
AB  - Paclitaxel is able to cause cell death through the induction of apoptosis. Cell
      death characteristics for docetaxel have not yet been described in detail. We
      investigated four unselected human ovarian cancer cell lines for the sensitivity
      to a 1hr exposure to docetaxel and calculated the concentrations inhibiting 50%
      (IC(50)) and 90% (IC(90)) of cell growth. Of the cell lines A2780, H134, IGROV-1
      (all wild-type p53) and OVCAR-3 (mutant, mt p53) A2780 was most sensitive and
      OVCAR-3 least sensitive. Equitoxic drug concentrations representing IC(90) values
      (25-510nM) were applied for 1hr to measure cell cycle distribution, DNA
      degradation, and to count apoptotic cell bodies and cells with multifragmented
      nuclei at various time-points after drug exposure. H134, IGROV-1 and OVCAR-3
      showed a continued mitotic block up to at least 72hr and prolonged presence of
      cells with multifragmented nuclei. High percentages of apoptosis were calculated
      at 48hr and at later time-points. In contrast, A2780 cells accumulated in the S
      phase of the cell cycle and apoptosis was hardly present. The changes in the
      expression levels of p53, p21/WAF1, Bax and Bcl-2, were not predictive for
      docetaxel-induced apoptosis. Caspase-3 activation occurred only in cells with
      accumulation in the G2/M phase starting as early as 8hr in OVCAR-3. Prolonged Bcl
      2 phosphorylation was evident in OVCAR-3, visible at 24hr in H134 and IGROV-1,
      while this phenomenon did not occur in A2780. The mitogen-activated protein
      kinase pathway (JNKs/SAPKs or c-Jun N-terminal kinases/stress-activated protein
      kinases, JNK1/2; extracellular response kinase, ERK1/2; p38) did not seem to be
      directly involved in Bcl-2 phosphorylation or apoptosis. We conclude that
      docetaxel is able to activate caspase-3, induce Bcl-2 phosphorylation and
      apoptosis in cells that show a prolonged G2/M arrest, but cells may also die by a
      caspase-3-independent cell death mechanism.

PMID- 11992643
TI  - Investigations on the effects of oltipraz on the nucleotide excision repair in
      the liver.
AB  - Recent studies support the view that in addition to its effect on both phase I
      and phase II xenobiotic metabolizing enzymes, the synthetic chemopreventive agent
      oltipraz also increases the nucleotide excision repair (NER) which represents the
      major pathway of elimination of chemical carcinogen DNA adducts. Since most
      carcinogens are activated in the liver, we investigated the influence of oltipraz
      on NER activity of this target tissue by using two different approaches. First,
      we employed an assay based on the measurement of DNA repair in cisplatin-damaged
      plasmid DNA incubated in the presence of cell-free extracts prepared from either
      rat liver or human hepatoma HepG2 cells treated by oltipraz. Secondly, we
      analyzed the removal of aflatoxin B(1)-derived DNA adducts formed in primary
      human hepatocytes exposed to oltipraz after treatment with this mycotoxin.
      Whatever the strategy used, NER activity was not altered in liver cells. These
      data demonstrated that liver cells actively repair bulky DNA adducts by NER and
      that oltipraz does not influence their NER activity neither in vivo nor in vitro,
      consequently strongly suggesting that the chemopreventive agent oltipraz is
      acting before the initiation step of cancer development.

PMID- 11992644
TI  - Thenoyltrifluoroacetone, a potent inhibitor of carboxylesterase activity.
AB  - Thenoyltrifluoroacetone (TTFA), a conventional mitochondrial complex II
      inhibitor, was found to inhibit purified porcine liver carboxylesterase non
      competitively with a K(i) of 0.61x10(-6)M and an IC(50) of 0.54x10(-6)M. Both rat
      plasma and liver mitochondrial esterases were inhibited in a concentration
      dependent fashion. Results indicate that TTFA is a potent inhibitor of
      carboxylesterase activity, in addition to its ability to inhibit mitochondrial
      complex II activity. Therefore, caution is warranted in using TTFA as a
      mitochondrial complex inhibitor in combination with esterase substrates, such as
      fluorescence probes or vitamin E esters.

PMID- 11992645
TI  - Inhibition of crotoxin phospholipase A(2) activity by manoalide associated with
      inactivation of crotoxin toxicity and dissociation of the heterodimeric
      neurotoxic complex.
AB  - Crotoxin (CACB complex) is a convulsant heterodimeric neurotoxic phospholipase
      A(2) (PLA(2)). The role of phospholipid hydrolysis in its epileptogenic
      properties remains unresolved. We, thus, studied the effect of manoalide (MLD), a
      PLA(2) inhibitor, on the toxin catalytic activity and its central and peripheral
      toxicity. Incubation of crotoxin with MLD fully and irreversibly inactivated its
      enzymatic activity. Interestingly, crotoxin also lost its central neurotoxicity
      after intracerebroventricular injection and peripheral toxicity after intravenous
      administration. MLD-treated crotoxin prevented the high affinity binding of
      [125I]-radiolabeled crotoxin on rat cortex synaptic plasma membranes. Further
      analysis of MLD-treated crotoxin by non-denaturing PAGE and surface plasmon
      resonance indicated that the crotoxin complex was dissociated after MLD
      treatment. Although the loss of MLD-treated crotoxin peripheral neurotoxicity
      could not be attributed to this dissociation, the presence of free CA subunit
      might explain the observed competition in binding experiments. In conclusion, the
      dissociation of the crotoxin complex by MLD, as demonstrated in this study, did
      not permit to specify the role of the enzymatic activity in crotoxin
      epileptogenic properties. Other approaches would be required to resolve this
      question.

PMID- 11992646
TI  - Effect of isatin on nitric oxide-stimulated soluble guanylate cyclase from human
      platelets.
AB  - Isatin, an endogenous indole, has previously been shown to inhibit atrial
      natriuretic peptide (ANP)-stimulated particulate guanylate cyclase activity.
      Here, it was shown that it can be transported to human platelets where it
      inhibited nitric oxide (NO)-stimulated soluble guanylate cyclase activity
      obtained from human platelets. The effect was most pronounced at 10(-8)M isatin
      and is the most potent effect of isatin yet observed. The dose response curve was
      bell shaped with higher doses becoming less effective. The maximal inhibition
      observed was of 40%. Isatin had no effect on protoporphyrin IX-stimulated
      guanylate cyclase. Isatin-dependent regulation of ligand-stimulated guanylate
      cyclases is suggested to promote a stress-induced switch in metabolism.

PMID- 11992647
TI  - Induction of UDP-glucuronosyltransferase 1A8 mRNA by 3-methylcholanthene in rat
      hepatoma cells.
AB  - UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of a broad
      spectrum of endobiotic and xenobiotic compounds, which leads to the excretion of
      hydrophilic glucuronides via bile or urine. By a mechanism of exon sharing,
      isoforms of the UGT1 family are made from the complex gene locus by an
      alternative combination of one of the unique first exons with the other commonly
      used exons. This study demonstrates that the expression of the UGT1 gene UGT1A6,
      1A7 and 1A8 is regulated at the transcriptional level by 3-methylcholanthene (3
      MC) in rat hepatoma H-4-II-E cells. Following 3-MC treatment, there is a gradual
      increase in the amount of UGT1A6 and UGT1A7 mRNA to the maximum levels after 16hr
      of treatment. The induction effect of 3-MC led to the expression of UGT1A8 which
      has not been reported before. This induction is suppressed by the RNA synthesis
      inhibitor actinomycin D, indicating that the inducer does not act at the level of
      mRNA stabilization. Northern blot analysis showed a 4-fold increase in UGT1A8
      transcription after treatment with 3-MC. The prolonged treatment with the protein
      synthesis inhibitor did not affect the induction process. The results provide
      experimental evidence for a transcriptional control of UGT1A8 synthesis.
      Transcriptional activation of the UGT1A8 by 3-MC does not appear to require de
      novo protein synthesis. 3-MC dependent activation is probably the result of a
      direct action of the compound on the aryl hydrocarbon receptor complex (AhR).

PMID- 11992648
TI  - Modulation of mdr1a and CYP3A gene expression in the intestine and liver as
      possible cause of changes in the cyclosporin A disposition kinetics by
      dexamethasone.
AB  - We investigated the effect of dexamethasone (DEX) on the disposition kinetics of
      cyclosporin A (CyA) and the mechanism of this drug interaction. Rats were treated
      with DEX (1 or 75mg/kg per day, i.p.) once a day for 1-7 days, and the blood
      concentration of CyA was measured after an i.v. or p.o. dose of CyA (10mg/kg) at
      1.5hr after the last DEX treatment. In rats treated with a low dose of DEX
      (1mg/kg), the blood concentration of CyA after i.v. administration was unchanged
      compared with that of untreated rats, whereas the blood concentration after oral
      administration was significantly decreased, and this decrease was dependent on
      the duration of DEX administration. The total clearance (CL(tot)) of CyA was
      unchanged, but the bioavailability was significantly decreased to about one-third
      of that in DEX-untreated rats after 7 days of DEX treatment. At this time, the
      expression of mdr1a mRNA and P-gp in the liver and intestine was increased,
      whereas CYP3A2 was unaffected at both the mRNA and protein levels. In rats
      treated with a high dose of DEX (75mg/kg), the blood concentration of CyA was
      significantly decreased after both i.v. and p.o. administrations compared with
      those of untreated rats. The bioavailability of CyA was decreased, and the
      CL(tot) was significantly increased. The P-gp and CYP3A2 in the liver and
      intestine were increased at both the mRNA and protein levels. Our results
      indicate that the drug interaction between CyA and DEX is a consequence of
      modulation of P-gp and CYP3A2 gene expression by DEX, with differential dose
      dependence.

PMID- 11992649
TI  - Protective effects of Celecoxib on lung injury and red blood cells modification
      induced by carrageenan in the rat.
AB  - In the present study, we evaluated the effect of Celecoxib, a selective COX-2
      inhibitor, in an acute model of lung injury induced by carrageenan administration
      in the rats. Injection of carrageenan into the pleural cavity of rats elicited an
      acute inflammatory response characterized by: fluid accumulation in the pleural
      cavity which contained a large number of polymorphonuclear neutrophils (PMNs) as
      well as an infiltration of PMNs in lung tissues and subsequent lipid
      peroxidation, and increased production of prostaglandin E(2) (PGE(2)), tumor
      necrosis factor alpha (TNFalpha), and interleukin-1beta. All parameters of
      inflammation were attenuated by Celecoxib. Furthermore, carrageenan induced an
      upregulation of the adhesion molecules ICAM-1 and P-selectin, as well as
      nitrotyrosine and poly(ADP-ribose) synthetase (PARS) as determined by
      immunohistochemical analysis of lung tissues. The degree of staining for the ICAM
      1, P-selectin, nitrotyrosine and PARS was reduced by Celecoxib. These results
      clearly confirmed that COX-2 plays a critical role in the development of the
      inflammatory response by altering key components of the inflammatory cascade.
      Therefore, selective inhibitor of COX-2 such as Celecoxib, offers a therapeutic
      approach for the management of various inflammatory diseases.

PMID- 11992650
TI  - Regulation of cyclic AMP in rat pulmonary microvascular endothelial cells by
      rolipram-sensitive cyclic AMP phosphodiesterase (PDE4).
AB  - We report here studies on the regulation of the metabolism of adenosine 3',5'
      monophosphate (cAMP) in established and primary cultures of rat pulmonary
      microvascular endothelial cells (RPMVEC). Inhibition by rolipram, a selective
      inhibitor of cAMP phosphodiesterase (PDE) of the PDE4 gene family, was required
      to achieve maximal cAMP accumulation induced by direct or receptor-mediated
      adenylate cyclase activation when measured by [3H]-adenine prelabeling. Rolipram
      increased cAMP accumulation more effectively than did forskolin, isoproterenol,
      or adenosine derivatives alone, although extensive synergy was seen with combined
      agents. High-affinity PDE4 inhibitors, but not low-affinity or non-selective
      inhibitors, were effective inducers of cAMP accumulation in intact cells. The
      maximum effects (i.e. intrinsic activities) of these agents in the intact cell
      did not correlate with their in vitro PDE4 inhibitory affinities. RPMVEC were
      shown to express almost exclusively the PDE4 gene family isoforms A6 and B3.
      Guanosine 3',5'-monophosphate hydrolysis, observed in other types of endothelial
      cells was not found in early or late passage RPMVEC. Reverse transcription
      polymerase chain reaction identification of mRNAse supported these conclusions
      with the exception that PDE2 and PDE4D mRNA isoform transcripts were present.
      These studies also support the conclusion that the mechanism of rolipram reversal
      of rat lung ischemia-reperfusion-induced permeability involves PDE4 inhibition in
      the microvascular endothelial cells of the lung.

PMID- 11992651
TI  - Tissue levels of S-adenosylhomocysteine in the rat kidney: effects of ischemia
      and homocysteine.
AB  - Most S-adenosylmethionine (AdoMet)-dependent methyltransferases are regulated in
      vivo by the AdoMet/S-adenosylhomocysteine (AdoHcy) ratio, also termed as
      "methylation potential." Since adenosine inhibits in vitro AdoHcy hydrolysis and
      since adenosine tissue levels increase during hypoxia, it can be predicted that
      AdoHcy levels may increase in the rat kidney in parallel of those of adenosine.
      Therefore, the present investigation was performed to assess changes of renal
      AdoHcy and AdoMet tissue contents during ischemia and after administration of
      adenosine and homocysteine or both in the ischemic rat kidney. In anesthetized
      rats ischemia of the kidney was induced by renal artery occlusion for various
      time intervals. Adenosine and homocysteine were infused into the renal artery of
      the ischemic kidney. To induce a hyperhomocysteinemia homocysteine was
      continuously infused. The kidneys were removed and immediately snap-frozen.
      Tissue contents of AdoHcy, AdoMet, adenosine and adenine nucleotides were
      analyzed by means of HPLC. Under normoxic condition the tissue contents of
      AdoHcy, AdoMet and adenosine were 0.7+/-0.05, 44.1+/-1.0 and 3.8+/-0.1nmol/g wet
      weight, respectively. Renal ischemia for 30min resulted in an increase of AdoHcy
      levels from 0.7+/-0.05 to 9.1+/-0.6nmol/g wet weight and in a dramatic decrease
      of the AdoMet/AdoHcy ratio and energy charge from 65.1+/-5.6 to 2.8+/-0.2 and
      from 0.87+/-0.01 to 0.25+/-0.01, respectively. Application of exogenous adenosine
      into the ischemic kidney did not result in further AdoHcy accumulation. However,
      when homocysteine was infused into the ischemic kidney, AdoHcy increased five
      fold above control levels, during 5min ischemia. Systemic infusion of
      homocysteine leads to a reduction of the methylation potential also in the
      normoxic kidney. We conclude that (i) the methylation potential in the kidney is
      markedly reduced during ischemia, mainly due to accumulation of AdoHcy; (ii)
      elevation of AdoHcy tissue content during ischemia is the result of the
      inhibition of AdoHcy hydrolysis; (iii) homocysteine is rate limiting for AdoHcy
      synthesis in the ischemic kidney; (iv) under normoxic conditions
      hyperhomocysteinemia can affect the methylation potential in the renal tissue.

PMID- 11992652
TI  - Picture reality decision, semantic categories and gender. A new set of pictures,
      with norms and an experimental study.
AB  - We present a new corpus of 80 pictures of unreal objects, useful for a controlled
      assessment of object reality decision. The new pictures were assembled from parts
      of the Snodgrass and Vanderwart [J. Exp. Psychol., Hum. Learning Memory 6; 1980:
      174] set and were devised for the purpose of contrasting natural categories
      (animals, fruits and vegetables), artefacts (tools, vehicles and furniture), body
      parts and musical instruments. We examined 140 normal subjects in a free-choice
      and a multiple-choice object decision task, assembled with 80 pictures of real
      objects and above 80 new pictures of unreal objects in order to obtain a
      difficulty index for each picture. We found that the tasks were more difficult
      with pictures representing natural entities than with pictures of artefacts. We
      found a gender by category interaction, with a female superiority with some
      natural categories (fruits and vegetables, but not animals), and a male advantage
      with artefacts. On this basis, the difficulty index we calculated for each
      picture is separately reported for males and females. We discuss the possible
      origin of the gender effect, which has been found with the same categories in
      other tasks and has a counterpart in the different familiarity of the stimuli for
      males and females. In particular, we contrast explanations based on socially
      determined gender differences with accounts based on evolutionary pressures. We
      further comment on the relationship between data from normal subjects and the
      domain-specific account of semantic category dissociations observed in brain
      damaged patients.

PMID- 11992653
TI  - Sensation of effort is altered in Huntington's disease.
AB  - In this study, we investigated sensation of effort in Huntington disease (HD). We
      tested the hypothesis that the basal ganglia are involved in processing effort
      sensation. The experimental paradigm consisted in a contralateral matching
      procedure where normal subjects (N=6) and HD patients (N=6) were required to lift
      a reference weight with their non-dominant index, and then compare the target
      weight with variable weights lifted by the dominant index. Two kinds of sequences
      were administered: (1) increasing, where the first weight was lighter than the
      reference weight and progressively increased in 20g steps, (2) decreasing, where
      trials started with a heavier weight and progressively decreased. We calculated
      the discrimination threshold (DT) across sequences as the weight for which the
      subject's response changed sign. The difference between the higher and the lower
      threshold was defined as "uncertain area". We predicted that controls should
      overestimate the reference weight lifted by their non-dominant hand because the
      same effort produces more force when applied to stronger muscles. If the basal
      ganglia mediates sensation of effort, patients' capability to discriminate
      weights should be degraded. As expected, normal subjects overestimated the
      reference weight lifted by their non-dominant index and showed a restricted
      uncertain area, thus, indicating that were able to discriminate minimal
      differences in generated forces. By contrast, patients with HD underestimated the
      reference weight lifted by their non-dominant hand and showed a broad uncertain
      area, thus, demonstrating that they could detect only important differences in
      the matched efforts. These results suggest that effort sensation critically
      involves the basal ganglia. In normal conditions, in parallel with the efferent
      command of force, an efferent copy reflecting the magnitude of the voluntary
      motor command is transmitted to sensory centres. This signal and/or the
      integration of sensory feedback which generates what is experienced as the sense
      of effort, would be altered in HD.

PMID- 11992654
TI  - The effect of left and right poses on the expression of facial emotion.
AB  - Research, using composite facial photographs has demonstrated that left-left
      composites are more emotionally expressive than are right-right composites. The
      present study investigated whether hemifacial asymmetries in expression are
      apparent in photographs, that feature one side of the face more than the other.
      Photographs were taken of the models who turned their heads: (a) 15 degrees to
      the left, (b) 15 degrees to the right or (c) faced directly towards the camera.
      It was predicted that left hemiface and midline photographs would be judged as
      more emotionally expressive than right hemiface photographs, where the left
      hemiface is less prominent. Three hundred and eighty-four participants viewed
      photographs of the three posing conditions, and rated each photograph along an
      emotional expressivity scale. Midline and left hemiface portraits were rated as
      more emotionally expressive than were right hemiface portraits. To investigate
      whether this effect was caused by observer's aesthetic/perceptual biases, mirror
      reversed versions of the three posing conditions were included. Left hemiface and
      midline portraits were rated as more emotionally expressive, irrespective of
      whether they were mirror-reversed. It was concluded that head turns of just 15
      degrees can bring about significant changes in the perceived emotionality. The
      relevance of these findings to painted portraits, which feature the left hemiface
      more than the right, is discussed.

PMID- 11992655
TI  - Coordinate and categorical judgements in spatial imagery. An fMRI study.
AB  - We aimed at verifying whether the hemispheric specialisation for
      categorical/coordinate spatial judgements also applies to the spatial imagery
      domain by the use of whole-brain fMRI. In a block-design experiment we used the
      "coordinate" mental clock test, contrasting it with a "categorical" task applied
      to the same clock stimuli; as a control task we used a syllable counting task
      requiring a verbal-phonological judgement on the same material of the two imagery
      tasks. Our results showed that categorical and coordinate spatial judgements on
      imagined stimuli rely on the activation of a set of cortical areas, centred upon
      the superior parietal lobule (SPL) bilaterally. These regions, together with
      other parietal and prefrontal areas, showed a pattern of relative lateralization,
      with the left hemisphere being mainly activated during the categorical task and
      the right in the coordinate task. These data confirm the strong involvement of
      the SPL in spatial processing. Moreover, our findings suggest that different
      interconnected neural networks are activated to comply with specific test
      requirements, giving rise to functional imaging patterns compatible with
      psychological theories on hemispheric specialization.

PMID- 11992656
TI  - Decision-making and addiction (part I): impaired activation of somatic states in
      substance dependent individuals when pondering decisions with negative future
      consequences.
AB  - Some substance dependent individuals (SDI) suffer from a decision-making
      impairment akin to that seen in neurological patients with lesions of the
      ventromedial (VM) prefrontal cortex. The somatic-marker hypothesis posits that
      decision-making is a process that depends on emotion and that deficits in
      emotional signaling will lead to poor decision-making. In this study, we tested
      the hypothesis that SDI who perform disadvantageously on a decision-making
      instrument, the gambling task (GT), have a deficit in the somatic signals that
      help guide their decision in the advantageous direction. Since deficits in
      decision-making/somatic markers can also result from dysfunctional amygdala, we
      asked indirectly (i.e. via tests sensitive to VM or amygdala dysfunction) whether
      such a deficit in SDI is restricted to VM dysfunction or includes the amygdala.
      Using the GT, and skin conductance response (SCR) as an index of somatic state
      activation, we studied groups of SDI (n=46), normal controls (n=49), and VM
      patients (n=10). A subgroup of SDI showed defective performance on the GT coupled
      with impaired anticipatory SCR, but normal SCR to punishment, and normal
      acquisition of conditioned SCR to an aversive loud sound. This supports the
      hypothesis that the poor decision-making in some SDI is associated with defective
      somatic state activation that is linked to a dysfunctional VM cortex. Thus, the
      dysfunctional VM cortex underlying the "myopia" for the future in some SDI may be
      one of the principle mechanisms underlying the transition from casual substance
      taking to compulsive and uncontrollable behavior.

PMID- 11992657
TI  - Decision-making and addiction (part II): myopia for the future or
      hypersensitivity to reward?
AB  - On a decision-making instrument known as the "gambling task" (GT), a subgroup of
      substance dependent individuals (SDI) opted for choices that yield high immediate
      gains in spite of higher future losses. This resembles the behavior of patients
      with ventromedial (VM) prefrontal cortex lesions. In this study, we addressed the
      possibility that hypersensitivity to reward may account for the "myopia" for the
      future in this subgroup of SDI. We used a variant version of the GT, in which the
      good decks yielded high immediate punishment but higher delayed reward. The bad
      decks yielded low immediate punishment and lower delayed reward. We measured the
      skin conductance response (SCR) of subjects after receiving reward (reward SCR)
      and during their pondering from which deck to choose (anticipatory SCR). A
      subgroup of SDI who was not impaired on the original GT performed normally on the
      variant GT. The subgroup of SDI who was impaired on the original GT showed two
      levels of performance on the variant GT. One subgroup (36% of the sample)
      performed poorly on the variant GT, and showed similar behavioral and
      physiological impairments to VM patients. The other subgroup of SDI (64% of the
      sample) performed normally on the variant task, but had abnormally large
      physiological responses to reward, i.e. large SCR after receiving reward (reward
      SCR) and large SCR in anticipation of outcomes that yield large reward. Thus, the
      combined cognitive and physiological approach of assessing decision-making
      characterizes three sub-populations of SDI. One sub-population is without
      impairments that can be detected by any measure of the GT paradigm. Another sub
      population is similar to VM patients in that they are insensitive to the future,
      both positive and negative. A third sub-population is hypersensitive to reward,
      so that the presence or the prospect of receiving, reward dominates their
      behavior.

PMID- 11992658
TI  - Haptic study of three-dimensional objects activates extrastriate visual areas.
AB  - In humans and many other primates, the visual system plays the major role in
      object recognition. But objects can also be recognized through haptic
      exploration, which uses our sense of touch. Nonetheless, it has been argued that
      the haptic system makes use of 'visual' processing to construct a representation
      of the object. To investigate possible interactions between the visual and haptic
      systems, we used functional magnetic resonance imaging to measure the effects of
      cross-modal haptic-to-visual priming on brain activation. Subjects studied three
      dimensional novel clay objects either visually or haptically before entering the
      scanner. During scanning, subjects viewed visually primed, haptically primed, and
      non-primed objects. They also haptically explored non-primed objects. Visual and
      haptic exploration of non-primed objects produced significant activation in
      several brain regions, and produced overlapping activation in the middle
      occipital area (MO). Viewing visually and haptically primed objects produced more
      activation than viewing non-primed objects in both area MO and the lateral
      occipital area (LO). In summary, haptic exploration of novel three-dimensional
      objects produced activation, not only in somatosensory cortex, but also in areas
      of the occipital cortex associated with visual processing. Furthermore, previous
      haptic experience with these objects enhanced activation in visual areas when
      these same objects were subsequently viewed. Taken together, these results
      suggest that the object-representation systems of the ventral visual pathway are
      exploited for haptic object perception.

PMID- 11992659
TI  - Relearning of verbal labels in semantic dementia.
AB  - Semantic dementia is a degenerative disorder of temporal neocortex characterised
      by loss of word and object concepts. There is limited evidence that temporary
      relearning of lost vocabulary may be possible, attributed to sparing of
      hippocampal structures. However, learning is variable across patients and factors
      underlying learning success are poorly understood. The study investigated
      relearning of object names in two severely anomic semantic dementia patients.
      Following memory models that assume that hippocampal memories require some
      neocortical representation to underpin them it was predicted that relearning
      would be influenced by patients' residual semantic information about stimuli.
      Experiment 1 confirmed that residual knowledge influenced learning success. On
      the assumption that neocortical knowledge encompasses concepts of space and time,
      as well as words and objects, it was predicted that learning would be affected by
      the availability of contextual (temporo-spatial) information. Experiment 2
      demonstrated effective learning of object names, attributed to the patient's use
      of temporal order and spatial position knowledge. Retention of object names over
      months was linked to the patient's capacity for autobiographical experiential
      (temporo-spatial contextual) association. The findings indicate that relearning
      of lost vocabulary is possible in semantic dementia, indicating a role of the
      medial temporal lobes in the acquisition of semantic information. Effective
      learning does not imply reinstatement of lost concepts, but, it is argued, does
      involve some reacquisition of meaning. The findings challenge the traditional
      semantic-episodic memory dichotomy and are consistent with a "levels of meaning"
      account of semantic memory.

PMID- 11992660
TI  - Saccadic distractibility in first-episode schizophrenia.
AB  - In the antisaccade paradigm, subjects are instructed to fixate a central point,
      and then move their eyes towards a position in space in the opposite direction
      but equidistant to a peripheral, sudden onset target. Antisaccade errors occur
      when subjects are "distracted" by the target and make a saccade towards it. These
      errors are more common in patients with schizophrenia but the underlying cause
      remains unclear. To determine whether antisaccade errors simply reflect a general
      inability to maintain fixation or are the consequence of a more specific deficit
      in the strategic control of internally generated actions, patients with first
      episode schizophrenia and healthy controls performed three saccadic paradigms
      which shared the core feature of requiring a prepotent saccade to be suppressed,
      but varied in their concurrent cognitive demands. We found that both groups
      showed an increase in errors as the cognitive demands increased across task.
      However, this increase was significantly steeper in the schizophrenic patients
      than in the controls. We also found that schizophrenic patients were as able as
      controls to inhibit prepotent saccades towards a target in a paradigm with no
      other cognitive demands. Possible explanations of these results include reduced
      working memory resources and impaired motor preparation in schizophrenia.

PMID- 11992661
TI  - Prose recall and amnesia: implications for the structure of working memory.
AB  - Two densely amnesic patients are shown to have good immediate but poor delayed
      prose recall, a result that presents problems for the current multi-component
      model of working memory. Examination of a wide sample of memory impaired patients
      suggests that this pattern occurs in densely amnesic patients who have well
      preserved intelligence and good executive capacities. Patients suffering from
      Alzheimer's disease typically show poor immediate and delayed prose recall,
      reflecting their combined intellectual and memory deficits. The results are
      interpreted in terms of a proposed new component of working memory, the episodic
      buffer.

PMID- 11992662
TI  - Is autotopoagnosia real? EC says yes. A case study.
AB  - We report a case of pure autotopagnosia (AT) following a left subcortical
      vascular accident. The absence of any language disorder, general mental
      deterioration or other cognitive impairments in this patient allowed an in-depth
      study of AT. Several tests of body representation and object and animal
      representation, as well as tests assessing semantic skills were administered to
      verify current interpretations of AT. Results showed a clear-cut dissociation
      between defective performances in body representation tests and normal
      performances on tests involving other kinds of stimuli. The patient's
      performances were particularly defective on tests relying on visuo-spatial body
      representation, but her semantic and linguistic knowledge seemed to be spared.
      This dissociation between different aspects of body representation supports
      Sirigu et al.'s hypothesis that multiple, partially independent systems are
      involved in body knowledge. In agreement with this hypothesis, in the present
      patient AT seems be due to a deficit in a system that processes the structural
      properties and relative position of single body parts. The present results,
      reporting the first observation of a subject not affected by any cognitive
      impairment other than AT, strongly support the existence of a system specifically
      devoted to body representation.

PMID- 11992663
TI  - On the use of fast blue, fluoro-gold and diamidino yellow for retrograde tracing
      after peripheral nerve injury: uptake, fading, dye interactions, and toxicity.
AB  - The usefulness of three retrograde fluorescent dyes for tracing injured
      peripheral axons was investigated. The rat sciatic was transected bilaterally and
      the proximal end briefly exposed to either Fast Blue (FB), Fluoro-Gold (FG) or to
      Diamidino Yellow (DY) on the right side, and to saline on the left side,
      respectively. The nerves were then resutured and allowed to regenerate.
      Electrophysiological tests 3 months later showed similar latencies and amplitudes
      of evoked muscle and nerve action potentials between tracer groups. The nerves
      were then cut distal to the original injury and exposed to a second (different)
      dye. Five days later, retrogradely labelled neurones were counted in the dorsal
      root ganglia (DRGs) and spinal cord ventral horn. The number of neurones labelled
      by the first tracer was similar for all three dyes in the DRG and ventral horn
      except for FG, which labelled fewer motoneurones. When used as second tracer, DY
      labelled fewer neurones than FG and FB in some experimental situations. The total
      number of neurones labelled by the first and/or second tracer was reduced by
      about 30% compared with controls. The contributions of cell death as well as
      different optional tracer combinations for studies of nerve regeneration are
      discussed.

PMID- 11992664
TI  - Retrieval of mRNA from paraffin-embedded human infant brain tissue for non
      radioactive in situ hybridization using oligonucleotides.
AB  - In situ hybridization (ISH) is used to examine the spatiotemporal distribution of
      gene expression in a range of tissues. Neuroscience research in human brain
      tissue requires techniques that can be used in formalin fixed and paraffin
      embedded tissue rather than frozen tissue which is recommended, but difficult to
      obtain. This study presents a method for non-radioactive (DIG) ISH for detecting
      NR1 gene expression, in human infant brain tissue. We compared three pre
      treatment effects, protease digestion, autoclaving (in citrate and Tris/EDTA
      buffer) and microwaving (in citrate and Tris/EDTA buffer). Tissue had been fixed
      in formalin for 2-12 weeks. Results were compared for the hybridization and
      background signal intensities, and tissue morphology. We found that optimum
      results were obtained using 12-min microwave pre-treatment in Tris/EDTA buffer.
      This method produced optimum signal to background ratio in infant and adult
      tissue, preserved tissue morphology, and was suitable for use across a broad
      range of fixation times.

PMID- 11992665
TI  - A method for obtaining 3-dimensional facial expressions and its standardization
      for use in neurocognitive studies.
AB  - Facial expressions of emotion are increasingly being used in neuroscience as
      probes for functional imaging and as stimuli for studying hemispheric
      specialization for face and emotion processing. Available facial stimuli are 2
      dimensional and therefore, their orientation is fixed and poorly suited for
      examining asymmetries, they are often obtained under poorly specified conditions,
      usually posed, lack ethnic diversity, and are of restricted age range. We
      describe a method for accurately acquiring and reconstructing the geometry of the
      human face and for display of this reconstruction in a 3-dimensional format. We
      applied the method in a sample of 70 actors and 69 actresses expressing
      happiness, sadness, anger, fear and disgust, as well as neutral expressions. Each
      emotion was expressed under three levels of intensity and under both posed and
      evoked conditions. Resulting images are of high technical quality and are
      accurately identified by raters. The stimuli can be downloaded in digital form as
      'movies' where angle and orientation can be manipulated for inclusion in
      functional imaging probes or in tests that can be administered as measures of
      individual differences in facial emotion processing. The database of emotional
      expressions can also be used as a standard for comparison with clinical
      populations.

PMID- 11992666
TI  - A novel electroencephalographic analysis method discriminates alcohol effects
      from those of other sedative/hypnotics.
AB  - Here we describe a mathematical and statistical signal processing strategy termed
      event resolution imaging (ERI). Our principal objective was to determine if the
      acute intoxicating effects of ethanol on spontaneous EEG activity could be
      discriminated from those of other sedative/hypnotics. We employed ERI to combine
      and integrate standard analysis methods to learn multiple signal features of time
      varying EEG signals. We recorded cortical EEG, electromyographic activity, and
      motor activity during intravenous administration of saline, ethanol (1.0 g/kg),
      chlordiazepoxide (10 mg/kg), pentobarbital (6 mg/kg), heroin (0.3 mg/kg), and
      methamphetamine (2 mg/kg) administered on separate days in six rats. A blind
      treatment of one of the drugs was readministered to validate the efficacy of ERI
      analysis. Significant changes in spontaneous EEG activity produced by all five
      drugs were detected by ERI analysis with a time resolution of 5-10 s. ERI
      analysis of spontaneous EEG activity also discriminated, with 90-95% accuracy, an
      ataxic dose of ethanol versus equivalent ataxic doses of chlordiazepoxide or
      pentobarbital, as well as the effects of saline, a reinforcing dose of heroin, or
      a locomotor activating dose of methamphetamine. ERI correctly matched the 'blind
      drug' as ethanol. These findings indicate that ERI analysis can detect the
      central nervous system effects of various psychoactive drugs and accurately
      discriminate the electrocortical effects of select sedative/hypnotics, with
      similar behavioral endpoints, but with dissimilar mechanisms of action.

PMID- 11992667
TI  - Patch clamp electrophysiology in nodose ganglia of adult rat.
AB  - The patch clamp technique is widely utilized for studying the
      electrophysiological properties of enzymatically isolated sensory neurons.
      Unfortunately, dissociation of the ganglion severs the afferent fibers. As a
      result, isolated neurons can only be broadly categorized according to somatic
      action potential waveforms, ion channel subtypes, chemical sensitivities and cell
      diameter. Such restricted classifications contrast with the continuum of
      conduction velocities (CVs), discharge patterns, sensory modalities and
      functional properties of visceral and spinal afferents. Previous reports of patch
      clamp recordings using intact ganglion have been limited to young animal
      preparations. This raises concerns regarding postnatal development and impedes
      the use of chronic models of disease or injury, which often necessitate the use
      of a more mature animal preparation. Here, we present a methodology for preparing
      nodose ganglion from adult rat (250-400 g) for study using the patch clamp
      technique. Successful whole cell recordings were obtained from approximately 50%
      of the cells selected for study, the majority of which had intact afferent
      fibers. Measures of somatic discharge and afferent fiber CV at both room and
      physiological temperatures were consistent with investigations using sharp
      microelectrodes. Voltage clamp recordings of whole cell Na(+), Ca(2+) and K(+)
      ion channel currents were comparable to those obtained using isolated neuron
      preparations. The ability to classify voltage- and ligand-gated ion channel type
      with afferent fiber CV in an adult preparation adds a valuable new dimension to
      cellular investigations of the diverse functional and chemical properties of the
      peripheral afferent nervous system.

PMID- 11992668
TI  - Cortical and subcortical lesions impair skilled walking in the ladder rung
      walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co
      ordination.
AB  - The ladder rung walking test is a new task to assess skilled walking and measure
      both forelimb and hindlimb placing, stepping, and inter-limb co-ordination. Rats
      spontaneously walk from a starting location to a goal along a horizontal ladder.
      The spacing between the rungs of the ladder is variable and can be changed to
      prevent the animal from learning either the absolute or relative location of the
      rungs. The testing procedure requires minimal training and allows detailed
      quantitative and qualitative analysis using video recording. The utility of the
      test is described with postoperative data obtained from animals with unilateral
      neocortical strokes produced by pial stripping over the motor cortex, neonatal
      and adult unilateral corticospinal tract lesions produced by tract section at the
      pyramids, and unilateral dopamine depletions produced by injection of 6
      hydroxydopamine into the nigrostriatal bundle. In addition, a group of aged rats
      was examined. Deficits in limb placing, stepping and co-ordination displayed by
      the animals demonstrate that this test can discriminate between lesions of the
      motor system or age-associated impairments. The test is useful for assessing loss
      and recovery of function due to brain or spinal cord injury, the effectiveness of
      treatment therapies, as well as compensatory processes through which animals
      adapt to nervous system injury.

PMID- 11992669
TI  - A dual-channel FM transmitter for acquisition of flight muscle activities from
      the freely flying hawkmoth, Agrius convolvuli.
AB  - Moths can perform various flight maneuvers by the contraction of some direct and
      indirect flight muscles. Multi-channel recording from these flight muscles and
      analysis of their interaction is very important for understanding insect flight
      motor system. In this study, we developed a dual-channel FM transmitter for
      acquisition of muscle potentials, with which a male hawkmoth (Agrius convolvuli)
      could fly freely and perform pheromone triggered zigzag flight in a wind tunnel.
      The transmitter weighs only 0.25 g including single battery, has a 5 m receivable
      range and works for more than 30 min. Doubling channels was achieved by providing
      two oscillators (the carrier frequencies were 82 and 85 MHz), and interference
      between them was overcome by buffer amplifiers and independent reference
      electrodes for each channel. With this transmitter, we could acquire muscle
      potentials from some direct and indirect muscles during free flight. Combined
      with simultaneous high-speed video analysis, we observed distinct changes of
      motor patterns during takeoff. Our radio-telemetric system allows acquisition of
      actual information from freely flying moths; such information will lead to
      further progress in the study of insect flight.

PMID- 11992670
TI  - Accurate quantitative RT-PCR for relative expression of Slo splice variants.
AB  - Much interest has been shown in the use of multi-template reverse transcription
      polymerase chain reaction (RT-PCR) as a quantitative instrument for low-abundance
      mRNAs. A desire to achieve finely-graded quantification of the stress- and
      hormone-related regulation of one splicing decision in an ion channel gene
      motivated us to test the reliability of simultaneous amplification of two splice
      variants with one pair of flanking constitutive primers. Unexpectedly
      indiscriminate heteroduplexing between the two amplification products, despite a
      large length difference, and their tight comigration with one homoduplex,
      mandated a rigorously-denaturing electrophoresis protocol. Conveniently, a new
      fluorescent dye with high affinity for single-stranded DNA has become available.
      Though the dye has a good dynamic range, we found that dye and gel saturation
      compounded by the length difference between products introduced an asymmetrical
      error into the calculation of relative abundance. Avoiding several pitfalls, dye
      calibration could be used to correct the error. We also found that differences in
      the amplification efficiency of the two templates were not constant, but
      dependent on the initial template ratio, requiring a non-linear correction.
      Together these improvements gave us very consistent quantitative results, and
      thus advance our analysis of hormonal mechanisms underlying the regulation of
      alternative splicing of an ion channel critically involved in stress responses.

PMID- 11992671
TI  - Automated analysis of foot-shock sensitivity and concurrent freezing behavior in
      mice.
AB  - Foot-shock is used in a variety of behavioral tasks either as a motivational
      stimulus, a way to characterize different rodents, or to test various
      pharmacological agents for their antinociceptive or analgesic effects. All these
      procedures need to assess foot-shock sensitivity either to rule out possible
      differences (when the shock is used as a motivational stimulus) or to use the
      differences to compare animals or treatments. In addition, many of the procedures
      that utilize foot-shock as a motivational stimulus evaluate freezing as an index
      of anxiety or fear. In the present study, data obtained by an automated computer
      system was compared with data obtained by human observers to validate the
      automated system for examining foot-shock sensitivity in mice. The different
      computer measures obtained for foot-shock sensitivity exhibited high correlations
      with human scoring at shock levels as low as 0.2 mA. The computer controlled
      analysis provided a non-subjective, quantifiable measurement of the foot-shock
      induced response as well as freezing behavior. Automated data collection is an
      improvement over the methods of human visual observation in that the data
      collection is more standardized, efficient and consistent.

PMID- 11992672
TI  - Extracellular detection of active membrane currents in the neuron-electrode
      interface.
AB  - Although measurement of sealing resistance is an important tool in the assessment
      of the electrical contacts between cultured cells and substrate embedded
      microelectrodes, it does not offer information about the type of cell, i.e.
      neuron or non-neuronal cell. Also, rules for translation of a measured sealing
      resistance into parameters for successful stimulation, i.e. eliciting an action
      potential, are not available yet. Therefore, a method is proposed for the
      detection of active membrane currents, elicited by extracellular current
      stimulation. The method is based on the prediction of the linear part of the
      response to an applied stimulus current pulse using an impedance model of the
      neuron-electrode contact. Active membrane currents are detected in the nonlinear
      response, which is obtained by subtraction of the predicted linear response from
      the measured response. The required impedance model parameters are extracted from
      impedance spectroscopy or directly from the measured responses.

PMID- 11992673
TI  - New mode of drug delivery: long term autonomous rhythmic hormone release across a
      hydrogel membrane.
AB  - This note demonstrates a novel mode of rhythmic drug delivery, which is
      independent of external modulation or physiological stimulation. Rhythmic
      behavior is attributed to negative, nonlinear feedback between the swelling state
      of a hydrogel membrane and the enzymatic conversion of glucose to hydrogen ion.
      The system pulsates in the presence of a constant level of glucose, thus
      distinguishing it from insulin delivery devices that respond to changes in
      glucose concentration. As an example, gonadotropin-releasing hormone (GnRH) was
      released in short, repetitive pulses over 1 week.

PMID- 11992674
TI  - Elongated supramolecular assemblies in drug delivery.
AB  - This review presents different lipid-based elongated microstructures: tubules,
      cochleate cylinders and ribbons. Their composition, process of preparation and
      the mechanism behind their formation is discussed as well as their use as a drug
      delivery system.

PMID- 11992675
TI  - Elucidation of the mechanism of incorporation of insulin in controlled release
      systems based on complexation polymers.
AB  - The objective of this study was to investigate the insulin incorporation and
      release properties of poly(methacrylic acid-g-ethylene glycol) P(MAA-g-EG)
      microparticles as a function of copolymer composition. These microparticles
      exhibited unique pH-responsive characteristics in which interpolymer complexes
      were formed in acidic media and dissociated in neutral/basic environments. The
      microparticles containing equimolar amounts of MAA and PEG were capable of
      efficient insulin loading using equilibrium partitioning (>90%). Additionally,
      insulin release from the gel was significantly retarded in acidic media while
      rapid release occurred under neutral/basic conditions. In contrast, as the amount
      of MAA of the polymer was increased, the entrapment efficiency of insulin within
      the gel greatly reduced and the insulin was readily released from the polymer
      network in the acidic and neutral/basic media. In addition, in order to evaluate
      the potential application of the microparticles to other drugs, theophylline,
      vancomycin, fluorescein-isothiocyanate-labeled dextrans (FITC-Ds) with average
      molecular weights of 4400 (FITC-D-4), 12,000 (FITC-D-10) and 19,500 (FITC-D-20)
      were utilized as model hydrophilic drugs. The incorporation profiles showed that
      the uptake of theophylline and vancomycin to the microparticles was lower than
      that of insulin. Additionally, polymer microparticles loaded with theophylline
      and vancomycin exhibited pH-sensitive release behavior, however, the oscillatory
      behavior is less pronounced than those of insulin. The values of drug
      incorporation ratio showed that the microparticles were capable of incorporating
      almost 90% of insulin and 15% of vancomycin from solution. On the other hand, the
      other hydrophilic drugs showed very low incorporation efficiency to the
      microparticles. These data suggest that gels containing equimolar amounts of
      MAA:EG have the potential to be used as an oral carrier of peptide drugs,
      especially for insulin.

PMID- 11992676
TI  - Physicochemical interaction of local anesthetics with lipid model systems-
      correlation with in vitro permeation and in vivo efficacy.
AB  - In dermal/transdermal drug administration stratum corneum (SC) is often the rate
      limiting step. Furthermore, the intercellular lipid domain of SC is nowadays
      widely accepted as the major contributor to the skin barrier. The current work
      investigates whether the difference in the level of topical efficacy of local
      anesthetic compounds correlates with the type of interaction between the drug and
      the intercellular lipids of SC. Therefore, local anesthetics of varying topical
      efficacy were evaluated with respect to their effect on the morphology of various
      model lipid systems using small and wide angle X-ray diffraction (SWAXD) and
      differential scanning calorimetry (DSC). The model lipids used were glyceryl
      monooleate, sphingomyelin and lipids isolated from human SC. Furthermore,
      partitioning into isolated human SC as well as permeation through isolated human
      SC and human tape-stripped skin were investigated in vitro. The results indicate
      that local anesthetics may act as their own permeation enhancers by increasing
      the degree of hydrocarbon chain fluidity of the intercellular lipids. Eventually
      these interactions may induce non-lamellar reversed types of liquid crystalline
      structures locally in SC, which further facilitate the drug mobility. The large
      difference in topical efficacy of the investigated local anesthetics could not be
      explained simply by looking at their effect on the phase behavior of lipid model
      systems. Despite the similarities in physicochemical properties of these
      substances, the in vitro skin permeability differed markedly
      (AD>EMLA>lidocaine>prilocaine>sameridine). Thus, it was concluded that sufficient
      drug permeability over SC is essential to obtain local anesthesia by blocking the
      superficial nociceptors.

PMID- 11992677
TI  - Three-layer guar gum matrix tablet formulations for oral controlled delivery of
      highly soluble trimetazidine dihydrochloride.
AB  - The present study is carried out to design oral controlled drug delivery systems
      for highly water-soluble drugs using guar gum as a carrier in the form of three
      layer matrix tablets. Trimetazidine dihydrochloride was chosen as a model drug
      because of its high water solubility. Matrix tablet granules containing 30% (M1),
      40% (M2) or 50% (M3) of guar gum were prepared by the wet granulation technique
      using starch paste as a binder. Three-layer matrix tablets of trimetazidine
      dihydrochloride were prepared by compressing on either side of guar gum matrix
      tablet granules of trimetazidine dihydrochloride M1, M2 or M3 with 200 mg of guar
      gum granules containing either 65% of guar gum (T1M1, T1M2 or T1M3), 75% of guar
      gum (T2M1, T2M2 or T2M3) or 85% of guar gum (T3M1, T3M2 or T3M3) as release
      retardant layers. The three-layer matrix tablets were evaluated for hardness,
      thickness, drug content uniformity, and were subjected to in vitro drug release
      studies. The amount of trimetazidine dihydrochloride released from the matrix and
      three-layer matrix tablets at different time intervals was estimated using a HPLC
      method. The three-layer guar gum matrix tablet (T3M3) provided the required
      release rate on par with the theoretical release rate for guar gum formulations
      meant for twice daily administration. The three-layer guar gum matrix tablet
      (T3M3) showed no change either in physical appearance, drug content or in
      dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. The DSC
      study did not show any possibility of interaction between trimetazidine
      dihydrochloride and guar gum/other formulation excipients used in the study. The
      results indicated that guar gum, in the form of three-layer matrix tablets, is a
      potential carrier in the design of oral controlled drug delivery systems for
      highly water-soluble drugs such as trimetazidine dihydrochloride.

PMID- 11992678
TI  - Release of tetracycline hydrochloride from electrospun poly(ethylene-co
      vinylacetate), poly(lactic acid), and a blend.
AB  - Electrospun fiber mats are explored as drug delivery vehicles using tetracycline
      hydrochloride as a model drug. The mats were made either from poly(lactic acid)
      (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two.
      The fibers were electrospun from chloroform solutions containing a small amount
      of methanol to solubilize the drug. The release of the tetracycline hydrochloride
      from these new drug delivery systems was followed by UV-VIS spectroscopy. Release
      profiles from the electrospun mats were compared to a commercially available drug
      delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast
      films of the various formulations.

PMID- 11992679
TI  - Microemulsion formulation for enhanced absorption of poorly soluble drugs. I.
      Prescription design.
AB  - Microemulsion formulations, which can be used to improve the bioavailability of
      poorly soluble drugs, were designed using only pharmaceutical excipients. Several
      types of oils and surfactants were tested and it was found that propyleneglycol
      monoalkyl ester and glycerol monoalkyl ester were solubilized easily in an
      aqueous medium by various types of surfactants. Although propyleneglycol dialkyl
      ester was difficult to be solubilized, the solubility was significantly enhanced
      by mixing it with glycerol monoalkyl ester at the ratio of 1:1. The most suitable
      surfactants for preparing microemulsion formulations were HCO-40, HCO-60, Tween
      80, BL-9EX and Pluronic P84. The use of additional surfactants such as sodium
      dodecyl sulfate or sodium deoxycholate significantly improved the solubilization
      capacity of the oils, although formulations free of these surfactants were also
      available. These microemulsion formulations can be administered as a form of
      water-in-oil microemulsion or surfactant-oil mixture, and are expected to convert
      to oil-in-water microemulsion in the small intestine.

PMID- 11992680
TI  - Microemulsion formulation for enhanced absorption of poorly soluble drugs. II. In
      vivo study.
AB  - Oral administration study of microemulsion formulations, which are known to
      improve the bioavailability of poorly soluble drugs, was performed using rats.
      Nitrendipine was used as a poorly soluble model drug, and its absorption was
      enhanced significantly by employing the microemulsion formulations compared to a
      suspension or an oil solution. The effect of the fed state on the oral absorption
      of nitrendipine became insignificant with the microemulsion formulations,
      although it affected the absorption from the suspension formulation
      significantly. The absorption behavior also varied with the type of surfactant.
      The absorption from Tween 80-based formulation was very rapid, while HCO-60-based
      formulation showed prolonged plasma concentration profile. However, the
      absorption from BL-9EX (polyoxyethylene alkyl ether)-based formulation was hardly
      observed. Damage to the gastrointestinal mucosa, which seems to be a serious
      problem of surfactant-based formulations, also differed with the type of
      surfactant employed. HCO-60 and Tween 80-based formulations were mild to the
      organs, while BL-9EX-based formulation caused serious damage. The behavior and
      absorption mechanism of the microemulsion formulations are discussed.

PMID- 11992681
TI  - Reverse iontophoretic monitoring in premature neonates: feasibility and
      potential.
AB  - Premature neonates represent a fragile patient population, often subjected to
      intensive clinical care and multiple drug therapy, which must be monitored
      carefully and continuously. The difficult and painful nature of repetitive blood
      sampling, particularly in this population, has provided considerable impetus for
      the development of noninvasive methods for monitoring blood analytes. Reverse
      iontophoresis, a relatively new technology already used for the transdermal
      monitoring of blood glucose levels in adults, may be particularly well-suited to
      exploit the unique properties of preterm neonatal skin. The underdevelopment of
      the premature infant's epidermis, and more specifically the stratum corneum (SC),
      results in an increased permeability to molecular transport. In this study, we
      have investigated the feasibility of reverse iontophoretic monitoring of two
      model drugs, caffeine and theophylline, which are often administered to premature
      neonates. To this purpose, tape-stripped porcine skin in vitro, which has been
      previously demonstrated to be an excellent model for premature neonatal skin, was
      employed. Reverse iontophoresis across intact membranes enabled a quantifiable
      extraction of both drugs predominantly at the cathode compartment. The mechanism
      of extraction of these essentially neutral drugs (caffeine and theophylline being
      uncharged at pH 7.4) was electroosmosis. However, when the SC was removed by
      progressive tape-stripping, the amounts of drugs extracted by reverse
      iontophoresis were equivalent to those obtained by passive diffusion. In these
      circumstances, therefore, the benefit and usefulness of the applied electric
      field had been lost. In summary, the absence of an at least partially functional
      skin barrier obviates, in the case of neutral molecules, the control (and
      directional transport) offered by iontophoresis; in contrast, for ionized
      species, where the principal iontophoretic transport mechanism is
      electromigration, the approach should be valid.

PMID- 11992682
TI  - Synthesis and release of 5-fluorouracil from poly(N-vinylpyrrolidinone) bearing 5
      fluorouracil derivatives.
AB  - 1-beta-allyloxycarbonyloxymethyl-5-fluorouracil (4) and 1,3-bis(beta
      allyloxycarbonyloxymethyl)-5-fluorouracil (5) were synthesised by reacting 5
      fluorouracil with formaldehyde followed by treating the product with isopropenyl
      chloroformate. The monomers 4 and 5 were copolymerized separately with N
      vinylpyrrolidinone to form linear copolymers and cross-linked polymer networks,
      respectively. The monomer reactivity ratios in the copolymerization of 4 with NVP
      were evaluated by both linear and non-linear methods and the effect of monomer
      feed composition on copolymer molecular weight was examined. The degradation of
      the polymer networks in phosphate buffer (pH 7.4) was investigated. The
      hydrolytic scission of the carbonate groups resulted in release of 5-fluorouracil
      and a decrease in cross-linking density. The time-dependent fractional release of
      the 5-FU could be fitted by a power relationship with exponents between 0.10 and
      0.25.

PMID- 11992684
TI  - Effect of sonication parameters on transdermal delivery of insulin to hairless
      rats.
AB  - Application of low-frequency ultrasound has been shown to enhance transdermal
      drug transport of large molecules such as insulin. In this study, we investigated
      the dependence of ultrasound-induced transdermal delivery of insulin on
      ultrasound parameters. Insulin was delivered in vivo to hairless rats using 20
      kHz ultrasound applied over a range of ultrasound intensity, application time and
      pulse length. Change in blood glucose levels of the animals was monitored to
      assess insulin transport. The results showed a threshold below which no
      detectable changes in blood glucose level was observed for each ultrasound
      parameter. Moreover, our findings indicated that sonophoretic enhancement is
      dependent on energy dose and length of ultrasound pulse that is consistent with a
      cavitation-based mechanism. The more significant effect of lowering glycemia was
      obtained with application of less than 15 min ultrasound and was similar to
      subcutaneous injection of 0.5 U of insulin. Pretreatment of hairless rat skin
      with ultrasound followed by application of insulin resulted in no significant
      modification in blood glucose level, indicating that transdermal transport of
      insulin mainly occurred during sonication. Sonophoresis may therefore potentially
      be applied for non-invasive and painless delivery of insulin in the treatment of
      insulin-dependent diabetes.

PMID- 11992683
TI  - HPMA-hydrogels containing cytostatic drugs. Kinetics of the drug release and in
      vivo efficacy.
AB  - This study proposes a strategy to generate new anticancer therapy using hydrogel
      based drug delivery systems to improve drug bioavailability and increase the
      therapeutic efficacy. We have synthesized biodegradable hydrogels based on N-(2
      hydroxypropyl)methacrylamide (HPMA) with prolonged drug release. Pharmacokinetic
      data from in vitro studies showed that the in vitro release of hydrophilic drugs
      (doxorubicin, vinblastine) from HPMA-hydrogels is affected mainly by drug
      diffusion and only partially by hydrogel degradation. The release of hydrophobic
      drugs (cyclosporine A, CsA) actually copies the process of degradation and
      therefore it is slower. Hydrogels with degradation time of 50 h released the
      doxorubicin over a period of at least 96 h after s.c. implantation. Drug
      concentration at pharmacologically active levels was maintained in the
      bloodstream over a period of at least 4 days, ranging between 0.1 and 1
      microg/ml. The therapeutic potential of HPMA-hydrogels in vivo was studied in
      Bcl1 leukemia. HPMA-hydrogels containing DOX were significantly more effective in
      inhibition of Bcl1 leukemia in comparison with free DOX or non-targeted polymeric
      drug (PK1). The efficacy of therapeutic combination using unspecific, hydrogel
      based therapy with specific, antibody-targeted therapy at late stages of Bcl1
      leukemia was also tested. In contrast to application of DOX alone, a cocktail of
      DOX with CsA as a blocker of P-glycoprotein (Pgp) incorporated into HPMA-hydrogel
      blocked the proliferation of Pgp-overexpressing multidrug resistant cell lines in
      vitro by induction of apoptosis.

PMID- 11992685
TI  - Terpenes in ethanol: haloperidol permeation and partition through human skin and
      stratum corneum changes.
AB  - Carvacrol, linalool and alpha-terpineol (5% w/v) in 50% ethanol were used to
      enhance the permeation of haloperidol (HP) through human skin in vitro and their
      enhancement mechanism was investigated with HP-stratum corneum (SC) binding
      studies, fourier transform infrared spectroscopy (FT-IR) and differential
      scanning calorimetry (DSC). Carvacrol followed by terpineol and linalool enhanced
      flux and permeability coefficient but only carvacrol provided the required plasma
      concentration and the permeated daily doses. All terpenes increased the activity
      coefficient of HP in the skin. Carvacrol increased the lag time, which could be
      due to slow redistribution within SC. The thermogram of hydrated SC showed two
      lipid endotherms T1 and T2 at 65 and 78 degrees C and protein endotherm T3 at 97
      degrees C. All endotherms were absent after SC treated for 48 h with 12 ml of
      terpene solutions and a decrease in melting points (m.p.) of lipids with a shift
      of protein endotherm were observed after 12 h treatment with 7 ml of terpene
      solutions. Linalool and terpineol decreased the m.p. of T1 to 33 degrees C.
      Carvacrol increased the T1 peak area, which was attributed to lateral lipid
      bilayer swelling. The IR spectra showed decreases in peak areas and heights of
      CH2 stretchings but did not show shift of these peaks, increase in their peak
      widths and shift in amide bands. All the three terpenes disrupted the lipid
      bilayer and extracted the lipids. Moreover, carvacrol increased the partition of
      HP whilst linalool and terpineol fluidized the lipids at skin temperature. There
      could be other possible protein-terpene interactions.

PMID- 11992686
TI  - Self-aggregates of poly(2-hydroxyethyl aspartamide) copolymers loaded with
      methotrexate by physical and chemical entrapments.
AB  - Amphiphilic copolymers based on poly(2-hydroxyethyl aspartamide) (PHEA) formed
      self-aggregates for the entrapment and release of methotrexate (MTX) by physical
      entrapment and chemical conjugation. In physical entrapment, MTX was partitioned
      into hydrophobic domains in self-aggregates of PHEA grafted with octadecyl chains
      (PHEA-C18) and the amount of the entrapped drug increased linearly by 3.39 mg per
      the degree of substitution of grafted octadecyl groups. The amphiphilic nature of
      the drug induced a large initial release in the buffer medium, irrespective of
      the amount of octadecyl chains. However, PEG-grafted PHEA-C18 copolymers
      conjugated with MTX, ConG, formed a micelle-like structure by self-association of
      the conjugates and suppressed the initial large release. The alkyl grafting
      lowered the CAC, meaning enhancement of aqueous stability. The release was
      accelerated in pH 10.0 by rapid hydrolysis of ester linkage by base-catalyzed
      cleavage, while it was significantly reduced at pH 5.0.

PMID- 11992687
TI  - In vivo release of bupivacaine from subcutaneously administered oily solution.
      Comparison with in vitro release.
AB  - A non-randomized cross-over study was performed with bupivacaine HCl (5 mg x ml(
      1)) aqueous solution and bupivacaine free base (4.44 mg x ml(-1)) in
      Viscoleo/castor oil 2:1 (v/v) administered s.c. to male Wistar rats. Plasma
      levels were analyzed by LC-MS. Plasma profiles obtained after administration of
      oily solution showed a prolonged bupivacaine release with lower peak plasma
      levels as compared to administration of an aqueous formulation applied in the
      same compartment. t(1/2), t(max), C(max) and AUC(0-infinity) for the aqueous
      solution were 63+/-8 min, 19+/-16 min, 194+/-46 ng x ml(-1) and 25,000+/-3000 ng
      min x ml(-1), respectively, while the corresponding data for the oil solution
      were 368+/-89 min, 334+/-186 min, 36+/-25 ng x ml(-1) and 25,000+/-6000 ng x min
      x ml(-1). The present data indicate the potential of designing an oil formulation
      of bupivacaine with a prolonged local analgetic effect exhibiting a minimum of
      systemic toxicity. In vivo release of bupivacaine from the oil solution was
      evaluated by a numerical deconvolution method. In vivo release kinetics was found
      to be first-order and corresponded well with in vitro release kinetics found
      using a rotating dialysis cell. This led to establishment of an in vitro/in vivo
      correlation for this particular formulation.

PMID- 11992688
TI  - Strength evaluation of transcriptional regulatory elements for transgene
      expression by adenovirus vector.
AB  - In studies of both gene function and gene therapy, transgene expression may be
      assisted considerably through the use of transcriptional regulatory elements with
      high activity. In this study, we evaluated the strength of various
      transcriptional regulatory elements both in vitro (six types of cell line) and in
      vivo (mouse heart, lung, kidney, spleen, and liver) by adenovirus-mediated gene
      transfer. In the case of the promoter/enhancer (P/E), the activity of CMV P/E
      (from the human cytomegalovirus immediate-early 1 gene) and hybrid CA P/E
      (composed of the CMV enhancer and chicken beta-actin promoter) were investigated,
      both of which are known to be strong and widely used. While hybrid CA P/E showed
      a higher transgene expression activity than CMV P/E, the addition of the intron A
      sequence (the largest intron of CMV) to CMV P/E increased the activity of CMV P/E
      to the same or higher level than that of hybrid CA P/E. Concerning the
      polyadenylation signal (P(A)) sequence, one from the bovine growth hormone (BGH)
      gene was about two times more efficient than that from the Simian virus 40 (SV40)
      late gene, both in vitro and in vivo. In the context of the CMV P/E containing
      the intron A sequence, a further increase in transgene expression was obtained by
      the addition of a SV40 enhancer downstream from the P(A) sequence. The
      combination of the SV40 P(A) and a SV40 enhancer showed almost comparable
      activity to BGH P(A). This information would be helpful for the construction of
      adenovirus vectors for studies regarding both gene function and gene therapy.

PMID- 11992689
TI  - Influence of water soluble fillers in hydroxypropylmethylcellulose matrices on in
      vitro and in vivo drug release.
AB  - The purpose of this study was to investigate the effect of fillers in gel-forming
      matrix on in vivo drug release after oral dosing. A further purpose was to
      predict the in vivo performance from in vitro dissolution test. Three controlled
      release acetaminophen tablets containing hydroxypropylmethylcellulose (HPMC) with
      or without highly water soluble fillers, lactose or polyethylene glycol 6000
      (PEG6000), were prepared. Water penetration into the matrix was enhanced by
      addition of fillers in the matrices, but the three tablets showed similar in
      vitro dissolution profiles, indicating that fillers in the HPMC matrices little
      affected the in vitro drug release. In contrast, the fillers in HPMC matrices did
      affect the in vivo performance in dogs. The absorption profile of HPMC matrix
      with PEG6000 was the fastest, followed by that with lactose and without water
      soluble filler, in that order. As the matrix with PEG6000 had a large amount of
      water and gelated a large portion of the matrix when in contact with water, the
      gel layer would be disintegrated by the gastrointestinal motility. It was found
      that dissolution of gel-forming HPMC matrices under mechanical stress by glass
      beads well correlated with the in vivo performance of the matrix, with little
      correlation by the conventional paddle method.

PMID- 11992690
TI  - Topical immunization using nanoengineered genetic vaccines.
AB  - DNA vaccines have been shown to elicit both broad humoral and cellular immune
      responses. Needle-free injection devices and the gene gun have been used to
      deliver these DNA vaccines to dendritic cells in the viable skin epidermis with
      some success. However, more cost-effective and dendritic cell (DC)-targeted
      immunization strategies are sought. To this end, a nanoengineered genetic vaccine
      for simple topical application was developed. Expressed beta-galactosidase was
      used as a model antigen. Plasmid DNA was coated on the surface of preformed
      cationic nanoparticles engineered directly from warm oil-in-water (O/W)
      microemulsion precursors comprised of emulsifying wax as the oil phase and CTAB
      as a cationic surfactant. Mannan, a DC ligand, was coated on the nanoparticles
      with and without entrapped endosomolytic agents, dioleoyl
      phosphatidylethanolamine (DOPE) and cholesterol. In-vitro cell transfection
      studies were performed to confirm transgene expression with these pDNA-coated
      nanoparticles. An in-vitro Concanavalin A (ConA) agglutination assay confirmed
      the presence of mannan on the surface of nanoparticles. The humoral and
      proliferative immune responses were assessed after topical application of these
      nanoengineered systems to the skin of shaved Balb/C mice. All pDNA-coated
      nanoparticles, especially the mannan-coated pDNA-nanoparticles with DOPE,
      resulted in significant enhancement in both antigen-specific IgG titers (16-fold)
      and splenocyte proliferation over 'naked' pDNA alone.

PMID- 11992691
TI  - Influence of polymer architecture on the structure of complexes formed by PEG
      tertiary amine methacrylate copolymers and phosphorothioate oligonucleotide.
AB  - The influence of polymer structure on the characteristics of complexes of a
      phosphorothioate antisense oligonucleotide (ISIS 5132) was studied, using well
      defined cationic copolymers based on 2-(dimethylamino) ethyl methacrylate
      (DMAEMA) and poly(ethylene glycol) (PEG). The three related copolymer structures
      were: DMAEMA-PEG (a diblock copolymer) DMAEMA-OEGMA 7 (a brush-type copolymer),
      DMAEMA-stat-PEGMA (a comb-type copolymer); each of these were examined together
      with DMAEMA homopolymer, which served as a control. The results revealed that all
      the polymers exhibited good binding ability with the oligonucleotide (ON).
      Interestingly, the comb-type polymer DMAEMA-stat-PEGMA demonstrated the highest
      binding ability and DMAEMA homopolymer the lowest, as judged by a dye
      displacement assay. DMAEMA homopolymer produced large agglomerates of smaller
      individual complexes as observed by optical density, photon correlation
      spectroscopy and transmission electron microscopy studies. In contrast, two PEG
      block copolymers, DMAEMA-PEG and DMAEMA-OEGMA 7, formed compact complexes of 80
      150 nm which had good long-term colloidal stability. This is attributed to the
      steric stabilisation effect of the PEG chains on the ON-copolymer complexes.
      These two copolymers are believed to form complexes with ON that have a micellar
      structure. Comb-type DMAEMA-stat-PEGMA copolymer formed highly soluble complexes
      with the ON that did not phase separate from the buffer solution. This study
      clearly demonstrates that varying the copolymer architecture allows access to a
      range of ON complexes. In vitro cytotoxicity experiments on HepG2 cells showed
      that all of the tertiary amine methacrylate copolymers displayed lower
      cytotoxicity than the control poly(L-lysine).

PMID- 11992692
TI  - Physical properties and in vitro transfection efficiency of gene delivery vectors
      based on complexes of DNA with synthetic polycations.
AB  - Biophysical properties of polycation/DNA complexes designed for gene delivery
      were studied with respect to the conditions of their preparation, chemical
      structure and molecular weight of the polycations involved. The polycations used
      included a variety of cationic polymers and copolymers containing primary and
      tertiary amino or quaternary ammonium groups. It was found that the molecular
      weight and the size of these polyelectrolyte complexes (PECs) increase with
      increasing temperature and pH of the buffer. By decreasing the molecular weight
      of polycations used for PEC formation, the complexes become unstable towards
      coagulation in aqueous solution at lower pH. The self-assembly of DNA with low
      molecular-weight polycations in water provides PECs with the lowest molecular
      weight, smallest size and the lowest density but their stability in NaCl
      solutions is very poor. Despite the complexity of the multistep transfection
      process, a direct correlation between the transfection efficiency in vitro and
      the stability of the complexes in NaCl solutions and coagulation in 0.15 M NaCl
      solution was found. DNA complexes with polycations containing primary amino
      groups showed the best stability in saline solutions and also the best
      transfection activity. PECs formed by polycations with quaternary ammonium groups
      were the least resistant to destruction by the added salt and provided the lowest
      activity in transfection assays. The highest transfection activity was found for
      DNA complexes formed with a statistical copolymer containing primary and tertiary
      amines.

PMID- 11992698
TI  - Explosibility boundaries for fly ash/pulverized fuel mixtures.
AB  - Incomplete combustion and subsequent fuel contamination of a waste stream can
      pose a serious explosion hazard. An example of this type of incident is the
      contamination of fly ash with unburned pulverized coal. The coal, if present in
      sufficient quantities in the mixture, can act as a fuel source for a potential
      explosion. Experiments were conducted in a 20l Siwek explosibility test chamber
      to determine the minimum fuel contamination of fly ash required to form an
      explosible mixture. A sample of fly ash from Ontario Power Generation (OPG)
      (Ont., Canada) was artificially contaminated with Pittsburgh pulverized coal dust
      (the surrogate used to represent unburned fuel dust). Additionally, the influence
      of fly ash particle size on the amount of fuel contaminant required to form an
      explosible mixture was examined. Fine and coarse size fractions of fly ash were
      obtained by screening the original sample of OPG fly ash. The results show that
      at least 21% Pittsburgh pulverized coal (or 10% volatile matter) was required to
      form an explosible mixture of the original fly ash sample and coal dust. The
      results also illustrate that fly ash particle size is important when examining
      the explosibility of the mixture. The fine size fraction of fly ash required a
      minimum of 25% coal dust (12% volatile matter) in the mixture for explosibility,
      whereas the coarse fly ash required only 10% coal dust (7% volatile matter).
      Thus, the larger the particle size of the inert fly ash component in the mixture,
      the greater the hazard.

PMID- 11992699
TI  - Effectiveness of commercial reagents for heavy metal removal from water with new
      insights for future chelate designs.
AB  - Toxic heavy metals in air, soil, and water are global problems that are a growing
      threat to the environment. To meet the federal and state guidelines for heavy
      metal discharge, companies often use chemical precipitation or chelating agents.
      In order to be competitive economically, many of these chelating ligands are
      simple, easy to obtain, and, generally offer weak bonding for heavy metals.
      Laboratory testing of three commercial reagents, trimercaptotriazine (TMT), Thio
      Red potassium/sodium thiocarbonate (STC), and HMP-2000 sodium
      dimethyldithiocarbamate (SDTC) has shown that the compounds were unable to reduce
      independent solutions containing 50.00 ppm of divalent cadmium, copper, iron,
      lead, or mercury to meet EPA standards. Additionally, the compounds displayed
      high leaching rates and in some cases decomposed to produce toxic substances. In
      contrast, the studies demonstrate that a recently reported sulfur-containing
      multidentate ligand is both safe and effective for the removal of these metals.

PMID- 11992700
TI  - Effects of ferrous iron and molecular oxygen on chromium(VI) redox kinetics in
      the presence of aquifer solids.
AB  - The kinetics and stoichiometry of the reduction of hexavalent chromium (Cr(VI))
      with ferrous iron (Fe(II)) were examined in systems with and without aquifer
      solids. Cr(VI) reduction was rapid in the absence of solids, but demonstrated
      slower and more complex kinetics in the presence of aquifer solids. The aquifer
      solids removed Fe(II) from solution and a portion of the reducing capacity of
      Fe(II) was transferred to the aquifer solids. The solid phases were then able to
      continue to remove Cr(VI). This suggests in situ treatment of Cr(VI) by Fe(II)
      injection would be feasible in the aquifer environment. In general, re-oxidation
      of reduced chromium by molecular oxygen was not observed in our systems over time
      periods of nearly 1 year, suggesting that the potential for chromium
      solubilization under these oxidizing conditions will be low. An empirical model
      was developed to describe the reduction kinetics of Cr(VI) in the presence of
      solids. The model assumes that the reaction is brought about by pseudo-species of
      iron that react instantaneously, rapidly and slowly with Cr(VI). A fourth pseudo
      species is assumed to be non-reactive. Model coefficients were determined by non
      linear regression. The model was able to describe observed concentrations of
      chromium well, but analysis of model errors indicated the potential existence of
      a distribution of species with different reaction rates rather than just three
      distinct species. Another model was developed to predict concentrations of
      different pseudo-species depending on the total amount of Fe(II) added and the
      amount of aquifer solids present. This model assumed that pseudo-species could
      result from intrinsic characteristics of the aquifer solids as well as being
      formed by addition of Fe(II), which could sorb to the aquifer solids.

PMID- 11992701
TI  - Removal of mercury(II) from aqueous solutions and chlor-alkali industry effluent
      by steam activated and sulphurised activated carbons prepared from bagasse pith:
      kinetics and equilibrium studies.
AB  - The adsorption of mercury from aqueous solutions and chlor-alkali industry
      effluent on steam activated and sulphurised steam activated carbons prepared from
      bagasse pith have been studied comparatively. The uptake of mercury(II) (Hg(II))
      was maximum by steam activated carbon in presence of SO(2) and H(2)S (SA-SO(2)
      H(2)S-C) followed by steam activated carbon in presence of SO(2) (SA-SO(2)-C),
      steam activated carbon in presence of H(2)S (SA-H(2)S-C) and steam activated
      carbon (SA-C) at the same concentration, pH and temperature of the solution.
      Adsorption experiments demonstrate that the adsorption process corresponds to the
      pseudo-second-order kinetic model and equilibrium results correspond to the
      Langmuir adsorption isotherm. Kinetic parameters as a function of initial
      concentration, for all adsorbents were calculated. Batch studies indicated that
      the optimum pH range for the adsorption of Hg(II) on sulphurised carbons was
      between 4 and 9 and for sulphur free carbon was between 6 and 9 at 30 degrees C.
      The adsorptive behaviour of the activated carbons is explained on the basis of
      their chemical nature and porous texture. Decrease in ionic strength and increase
      in temperature of the solution has been found to improve the uptake of Hg(II).
      Synthetic and chlor-alkali industrial wastewaters were also treated by
      sulphurised activated carbons to demonstrate their efficiencies in removing
      Hg(II) from wastewaters. Some feasibility experiments have been carried out with
      a view to recover the adsorbed Hg(II) and regenerate the spent activated carbons
      using 0.2M HCl solution. The data obtained point towards viable adsorbents, which
      are both effective as well as economically attractive for Hg(II) removal from
      wastewaters.

PMID- 11992702
TI  - Studies on adsorptive removal of Co(II), Cr(III) and Ni(II) by IRN77 cation
      exchange resin.
AB  - The adsorption of cobalt, chromium and nickel from aqueous solutions on IRN77
      cation-exchange resin has been studied comparatively. The percentage removal of
      cobalt, chromium and nickel was examined by varying experimental conditions, viz.
      dosage of adsorbent, pH of the solution and contact time. It was found that more
      than 95% removal was achieved under optimal conditions. The adsorption capacity
      (k) for cobalt, chromium and nickel were calculated from the Freundlich
      adsorption isotherm. The adsorption of cobalt, chromium and nickel on this cation
      exchange resin followed the Lagergren kinetic model. Also the competitive
      adsorption of multi-metals onto the IRN77 resin was studied. The studies showed
      that this cation-exchange resin can be used as an efficient adsorbent material
      for the removal of cobalt, chromium and nickel from water and nuclear power plant
      coolant water.

PMID- 11992703
TI  - Stabilization/solidification (S/S) of mercury-containing wastes using reactivated
      carbon and Portland cement.
AB  - Stabilization/solidification (S/S) of mercury-containing solid wastes using
      activated carbon and cement was investigated in this study. The activated carbon
      used in the study was a powder reactivated carbon (PAC). The effect of sulfur
      treatment of the PAC was also studied. It was found that PAC was effective in
      stabilizing Hg in the waste surrogate. Pretreatment of the PAC by soaking it in
      CS(2) significantly improved the mercury adsorption capacity of the PAC. The
      adsorption equilibrium was reached within 24h. The optimum pH for the reaction
      was within the range of 5.0-5.5. After mercury stabilization by adsorption on the
      reactivated carbon, the Hg waste surrogate was mixed with Portland cement for
      solidification. Surrogates with up to 1000 mg/kg Hg were stabilized and
      solidified well enough to pass the TCLP test. The adsorption of mercury by
      reactivated carbon was in accordance with the Freundlich isotherm. Cement
      solidification of reactivated carbon-stabilized surrogates, significantly reduced
      the often-reported interference by chloride ions, by forming a barrier outside of
      the carbon particles. The S/S process using reactivated carbon and cement is an
      effective and economical technology for treating and disposing mercury-containing
      solid wastes.

PMID- 11992706
TI  - Prevalence of and risk factors involved in the spread of neonatal bovine
      cryptosporidiosis in Galicia (NW Spain).
AB  - An epidemiological study was carried out on farms in Galicia (NW Spain) to
      investigate the prevalence of and the risk factors associated with the spread of
      infection by Cryptosporidium parvum in calves of less than 3 weeks of age. A
      total of 22 cattle farms (10 beef herds and 12 dairy herds) were visited once
      every 21 days between January and December 2000. A faecal sample was collected
      directly from the rectum of each of the 844 calves born during the study period.
      Each sample was studied macroscopically to establish its consistency as liquid,
      soft or solid, and the presence of mucus or blood noted. C. parvum oocysts were
      identified by direct microscopic examination and the intensity of infection
      established semiquantitatively as slight, moderate or severe. Of the 844 calves,
      404 were found to have the parasite in their faeces, i.e. the prevalence was
      47.9%. Statistical analysis of the risk factors such as general characteristics
      of the farm and the housing conditions of the calves, revealed three variables
      that significantly effect the risk of cryptosporidial infection in suckling
      calves: the method of cleaning, the type of flooring and the frequency of
      cleaning.

PMID- 11992707
TI  - A study of cryptosporidiosis in a cohort of neonatal calves.
AB  - During calving time on an experimental farm, 32 newborn calves were selected at
      random and monitored for infection with Cryptosporidium parvum for the first 30
      days of their lives. The animals were fed pooled colostrum for 2-3 days after
      birth and housed in individual pens, which were washed daily using a pressure
      hose. Fecal smears were examined by microscopy after staining with carbol fuschin
      for visualization of oocysts. Oocyst shedding was scored semiquantitatively
      according to the average number of oocysts in 20 randomly selected fields at
      1000x magnification. All the animals acquired the infection before 18 days of
      age. The period of maximum risk was between 9 and 12 days; 50% of the animals
      were infected by 9.4 days of age. It was found that the earlier the animals
      acquired the infection, the longer the patent period. Oocyst shedding, which did
      not always begin with the onset of diarrhea, lasted between 8 and 23 days (mean
      12.4+/-3.3 days). Furthermore, fecal samples from 32 periparturient cows (within
      +/-7 days of giving birth) were filtered, concentrated and examined for oocysts
      using a fluorescent monoclonal antibody test, which revealed that six of the
      cows, although asymptomatic, were excreting C. parvum oocysts.

PMID- 11992708
TI  - Vaccination of donkeys against Babesia equi using killed merozoite immunogen.
AB  - Protective efficacy of a killed Babesia equi immunogen was assessed in donkeys.
      The immunogen was prepared from B. equi infected blood so as to contain lysate of
      2 x 10(10) parasitised erythrocytes per dose. The immunogen was mixed with an
      adjuvant Quil A (3mg) and inoculated into four susceptible donkeys (group I). A
      booster inoculation was given after 21 days of first inoculation followed by
      challenge with fresh infected blood containing 1x10(11) parasitised erythrocytes
      14 days later. Two groups of two donkey each were included as adjuvant only
      control (group II) and uninoculated control (group III), respectively. After
      challenge, donkeys were observed for a period of 4 weeks. The immunised donkeys
      (group I) showed significantly high (P<0.05%) enzyme linked immunosorbant assay
      (ELISA) antibody titres and significantly high (P<0.05%) stimulation indices (SI)
      in lymphocyte proliferation assay (LPA) than that of groups II and III donkeys
      from day 14 PI and day 7 PI onwards, respectively. All the immunised donkeys
      withstood lethal challenge, whereas, control donkeys died within 10 days post
      challenge (PC). Parasitaemia rose to mean maximum 8.0+/-6.0% for 5-7 days in
      group I donkeys after challenge, whereas, it rose to 55.5% in control groups. The
      percent rise in rectal temperature, total leucocyte count (TLC), fall in
      haemoglobin (Hb) was less severe in immunised group as compared to the control
      groups. Two immunised-challenged donkeys were splenectomised recovery. No
      parasites appeared in the blood during the observation period following
      splenectomy 4-week. Three times increase in skin-fold thickness at 24h of
      intradermal inoculation prior to challenge in group I donkeys was observed, thus,
      indicating a good in vivo cell mediated immunity. It can be concluded that the B.
      equi immunogen along with adjuvant Quil A, used in the present study, was optimum
      to elicit a strong immune response against B. equi in experimental donkeys.

PMID- 11992709
TI  - Immunological relationship between Neospora caninum and Besnoitia besnoiti.
AB  - Neospora caninum is a coccidian parasite identified as a major cause of abortion
      in cattle. A combined infection of N. caninum with another taxonomically related
      parasite of cattle, Besnoitia besnoiti can occur in geographical areas endemic
      for both species. Both infections are routinely diagnosed serologically, and
      incorrect diagnosis could occur if immunological cross-reactivity exists between
      the two parasites. To investigate the possible degree of cross-reactivity, we
      compared results obtained with two serological techniques, immunofluorescent
      antibody test (IFA), and Western blot analysis on known positive and negative
      sera. The test sera were derived from naturally infected cattle and from
      experimentally infected Mongolian gerbils. In IFA of bovine sera, no cross
      reactvity was detected at the commonly used serum dilution cutoffs of 1:200 for
      N. caninum and 1:256 for B. besnoiti. However, at 1:64 dilution of both cattle
      and gerbil sera, anti-N. caninum sera reacted with B. besnoiti antigen in some
      individual samples. Anti-B. besnoiti serum did not react with N. caninum antigen
      at any dilution. This low level one directional cross-reactivity was confirmed by
      Western blot analysis. B. besnoiti antigen showed two immunoreactive bands when
      probed with anti-N. caninum serum, while no bands appeared when N. caninum
      antigen was probed with B. besnoiti antiserum. Immunization and challenge
      experiments in the highly susceptible Mongolian gerbil (Meriones unguiculatus)
      showed essentially no cross-protection between N. caninum and B. besnoiti.

PMID- 11992710
TI  - Epidemiological survey of swine cysticercosis in two rural communities of West
      Cameroon.
AB  - To determine the prevalence of porcine cysticercosis, a survey was carried out in
      27 villages belonging to two rural communities of West-Cameroon (Bafou and
      Bamendou). Between January and August, 2000, a total of 707 pigs were examined
      serologically and by tongue inspection. Serum samples were examined for
      circulating parasite antigen using a monoclonal antibody-based sandwich enzyme
      linked-immunosorbent assay (Ag-ELISA) and for antibodies against cysticerci (Ab
      ELISA). Seventy eight samples (11.0%) were found positive in the Ag-ELISA and 154
      (21.8%) in the Ab-ELISA, while by tongue inspection on the same animals
      cysticerci were detected in 43 pigs (6.1%). Gibbs sampling using results of these
      three tests indicated that the estimated prevalence of porcine cysticercosis was
      10.9%. Analysis of the Ag-ELISA results demonstrated that adult pigs showed a
      significantly higher seroprevalence (15%) than young ones (8.4%). There was no
      statistical difference in cysticercosis prevalence in pigs raised in households
      with or without a latrine. Animals that were reported to be usually confined were
      significantly less infected (9.9%) than free-roaming pigs (16.2%). Infection
      rates were significantly higher in pigs that had access to human faeces (13.8%)
      than those which did not have access (9.1%). This study has identified some
      community behavioural and environmental practices that should be modified to
      prevent continuous transmission of porcine cysticercosis.

PMID- 11992711
TI  - Estimating genetic differences in natural resistance in Rhon and Merinoland sheep
      following experimental Haemonchus contortus infection.
AB  - Genetic parameters of natural resistance were estimated in Rhon and Merinoland
      (German Merino) sheep following experimental infection with Haemonchus contortus.
      A total of 133 Rhon and 244 Merinoland lambs descending from 5 and 6 rams,
      respectively, were evaluated. Each helminth-naive lamb was orally infected with
      5000 infective third-stage larvae (L(3)) of the nematode H. contortus at 12 weeks
      of age. Faecal egg counts (FEC) and haematocrit values were measured in all lambs
      at 16 and 20 weeks of age. Seventy-nine Merinoland and 29 Rhon male lambs were
      slaughtered immediately after the second sampling and worms were collected. Mean
      worm burden was calculated and the length of adults worms from an aliquot was
      measured.FEC of Rhon sheep was higher compared with Merinoland sheep (P<0.01). H.
      contortus L(3)-larvae specific antibody (IgL) level was higher in Rhon sheep
      (P<0.05). However, no differences in haematocrit, worm burden and IgG antibody
      values could be found between the breeds. Heritabilities for log FEC (+/-S.E.)
      were 0.0 and 0.07 (+/-0.07) for the first sample in Rhon and Merinoland sheep,
      respectively. Values for the second sample were higher in both breeds (Rhon
      0.35+/-0.14, P<0.05; Merinoland 0.17+/-0.07, P<0.05). Corresponding
      heritabilities for haematocrit were higher in Merinoland (0.56+/-0.20 and 0.51+/
      0.27) compared with Rhon (0.29+/-0.12 and 0.08+/-0.13). Heritabilities for worm
      burden were high in Rhon (0.54+/-0.2) and low in Merinoland (0.06+/-0.14 and
      0.11+/-0.15). Estimated values for IgL were between 0.13 (+/-0.11) for the first
      sample in both breeds and 0.30 (+/-0.18) for the second sample in Rhon sheep.
      Corresponding heritabilities for IgG were not different from 0.0 in both breeds
      (P>0.05). Positive phenotypic correlations were estimated for IgG and IgL values
      in both breeds (P<0.01). IgG was significantly (P<0.05) and positively correlated
      with worm burden in male Merinoland and IgL with worm burden in male Rhon sheep.

PMID- 11992712
TI  - Winter survival in Sweden of L(3)-stage larvae of the ostrich wireworm
      Libyostrongylus douglassii.
AB  - Libyostrongylus douglassii, a pathogenic trichostrongylid nematode of the
      ostrich, was recently identified as a potentially important parasite in ostriches
      on Swedish farms. This parasite is well adapted to the hot and dry climates of
      sub-Saharan Africa, the natural habitat of the ostrich. The influence of low
      temperatures in colder climates, such as in Sweden, on free-living stages of L.
      douglassii is however insufficiently known. In this study, parasite free ostrich
      faeces were mixed with infective L(3)-stage larvae of L. douglassii, which had
      been cultured from eggs obtained from two Swedish farms. Samples of the mixture
      were placed on a grass surface, and analyses for L(3)-stage larvae were performed
      at regular intervals. The results of the study showed that L(3)-stage larvae may
      remain alive during a period of at least 97 days on pasture during the winter
      season in Sweden, even when the temperature within the samples was repeatedly
      below -0.1 degrees C, and the air temperature varied between -19.6 and +14.9
      degrees C. It was concluded that L(3)-stage larvae of L. douglassii probably have
      the ability to remain viable on pastures during winter in Sweden.

PMID- 11992713
TI  - Electron microscopic and molecular identification of Wolbachia endosymbionts from
      Onchocerca lupi: implications for therapy.
AB  - It was recently demonstrated that Wolbachia intracellular bacteria (alpha 2
      proteobacteria, Rickettsiales) living in filarial nematodes are obligatory
      symbionts of their hosts. Herein, we report the electron microscopic and 16S
      ribosomal DNA-based (16S rDNA) identification of the endobacteria harboring in
      Onchocerca lupi. The worm nodules containing the nematodes were removed from
      three Hungarian dogs naturally infected with O. lupi. Wolbachia-like endobacteria
      were detected by electron microscopy in the lateral chords of both adult worms
      and microfilariae. The endosymbionts in O. lupi resemble in location, size, and
      morphology the wolbachiae found in other filariae. The presence of wolbachiae in
      O. lupi was also confirmed by PCR amplification of the 16S rDNA of the bacteria.
      The 16S rDNA-based phylogenetic analysis revealed that the endosymbionts of O.
      lupi infecting dogs belong to the supergroup C of Wolbachia pipientis and are not
      identical with those of other Onchocerca spp. sequenced so far. Since
      intermittent treatment with oxytetracycline has adulticid and microfilaricid
      activity by depletion of Wolbachia endobacteria, this antibiotic treatment
      regimen may offer an alternative of ivermectin or diethylcarbamazine in the
      suppression of postoperative microfilaridermia in Onchocerca-infected dogs and
      may prevent relapse.

PMID- 11992714
TI  - Western blot analysis of the humoral response of dogs experimentally infected
      with Angiostrongylus vasorum (Baillet, 1866).
AB  - Seven cross-bred dogs were inoculated with Angiostrongylus vasorum and serum
      samples were analyzed using the enzyme-linked immunosorbent assay (ELISA) and
      Western blot (WB). ELISA detected specific antibodies anti-A. vasorum, from 14 to
      28 days after inoculation (DAI) and persisted throughout the experiment. Using
      WB, the main antigens detected had molecular weight of approximately 115, 102,
      86, 76, 69, 56, 41, 32, 28, 20-22 and 10kDa.

PMID- 11992715
TI  - In vitro acaricidal effect of plant extract of neem seed oil (Azadirachta indica)
      on egg, immature, and adult stages of Hyalomma anatolicum excavatum (Ixodoidea:
      Ixodidae).
AB  - Effects of the plant extract of neem seed (Azadirachta indica) on eggs, immature,
      and adult stages of Hyalomma anatolicum excavatum was studied at concentrations
      of 1.6, 3.2, 6.4, and 12.8%. The extract was found to have a significant effect
      on the hatching rate of eggs. It significantly increased the hatching rate during
      the first 7 days post-treatment (DPT) giving incompletely developed and dead
      larvae; however, it cause hatching failure at DPT 15. Neem Azal F induced a
      significant increased in mortality rates of newly hatched larvae, unfed larvae,
      and unfed adults reaching 100% on 15th, 3rd, and 15th DPT, respectively. The
      mortality rates increased with the extract concentrations. Although, it had no
      significant effect on the moulting rates of fed nymphs, it caused malformation or
      deformities in 4% of adults moulted. It was concluded that the concentration of
      Neem Azal F which may be used for commercial control of this tick species were
      1.6 and 3.2%.

PMID- 11992716
TI  - Papers presented at the workshop "Comparative Developmental Biology". Naples,
      Italy. April 17-23, 2001.

PMID- 11992717
TI  - Morphometrics and the role of the phenotype in studies of the evolution of
      developmental mechanisms.
AB  - Developmental mechanisms are usually assumed to evolve by natural selection of
      the morphological traits they produce. Therefore, information on phenotypic
      traits is an important component of comparative studies of development.
      Morphometrics permits the rigorous quantitative analysis of variation in
      organismal size and shape, and is increasingly being used in developmental
      contexts. The new methods of morphometrics combine a geometric concept of shape
      with the procedures of multivariate statistics, and constitute a powerful and
      flexible set of tools for analyzing morphological variation. This paper briefly
      reviews these methods and provides examples of their application in studies of
      genetic variation and developmental modularity. The results of morphometric
      analyses can be readily interpreted in relation to the geometry and anatomical
      structure of the parts under study. Genetic studies of shape in the mouse
      mandible found two recurrent patterns in environmental and genetic variation from
      different origins, suggesting that the development system 'channels' the
      phenotypic expression of variation in similar ways. Moreover, by analyzing the
      correlations of left-right asymmetries of morphometric traits, it is possible to
      delimit the spatial extent of developmental modules. These methods complement the
      experimental approaches of developmental biology and genetics, and can be
      expected to be especially fruitful in combination with them.

PMID- 11992718
TI  - A Twist in fate: evolutionary comparison of Twist structure and function.
AB  - The general requirement to induce mesoderm and allocate cells into different
      mesodermal tissues such as body muscle or heart is common in many animal embryos.
      Since the discovery of the twist gene, there has been great progress toward
      unraveling the molecular mechanisms that control mesoderm specification and
      differentiation. Twist was first identified in Drosophila as a gene crucial for
      proper gastrulation and mesoderm formation. In the fly embryo, Twist continues to
      play additional roles, allocating mesodermal cells into the body wall muscle fate
      and patterning a subset of these muscles. Twist is also required for proper
      differentiation of the adult musculature. Twist homologues have been identified
      in a great variety of organisms, which span the phylogenetic tree. These
      organisms include other invertebrates such as jellyfish, nematode, leech and
      lancelet as well as vertebrates such as frog, chick, fish, mouse and human. The
      Twist family shares both homology in structure across the basic helix-loop-helix
      domain and in expression during mesoderm and muscle development in most species.
      Here we review the current state of knowledge of the Twist family and consider
      how Twist functions during development. Moreover, we highlight experimental
      evidence that shows common themes that Twist employs during specification and
      patterning of the mesoderm among evolutionarily distant organisms. Conserved
      principles and the molecular mechanisms underlying them are discussed.

PMID- 11992719
TI  - Formation of the head-trunk boundary in the animal body plan: an evolutionary
      perspective.
AB  - Gene expression analyses and anatomical studies suggest that the body plans of
      protostomes and deuterostomes are phylogenetically related. In the central
      nervous system (CNS), arthropods and vertebrates (as well as their closest
      related phyla the urochordates and cephalochordates) share a nerve cord with
      rostral specification: the cerebral neuromeres in Drosophila, cerebral sensory
      vesicle of ascidians and lancelets and the large brain of craniates. Homologous
      genes, in particular of the otd/Otx and Hox families, are at play in these
      species to specify the anterior and posterior CNS territories, respectively. In
      contrast, homologies in the establishment of boundary regions like those
      separating head and trunk structures in arthropods or mid- and hindbrain domains
      in chordates are still unclear. We compare in these species the formation,
      properties and molecular characteristics of these boundaries during embryonic
      development. We also discuss recent findings suggesting that insects and
      vertebrates might have co-opted factors of related families to control the
      formation of these boundary regions, the evolution of which would then appear
      dramatically different from that of the anterior and posterior CNS domains.

PMID- 11992720
TI  - Role of the EGF-CFC gene cripto in cell differentiation and embryo development.
AB  - The EGF-CFC proteins have been recently recognized as a novel family of
      extracellular factors required during early vertebrate development. Cripto is the
      founder member of the EGF-CFC family initially related to the epidermal growth
      factor (EGF); its expression is increased in human colon, gastric, pancreatic and
      lung carcinoma and in different types of both mouse and human breast carcinomas.
      Genetic studies in the mouse have established an essential role of cripto in the
      formation and correct positioning of the anterior-posterior axis. Furthermore,
      the absence of cripto results in a defective precardiac mesoderm, unable to
      differentiate into functional cardiomyocytes. Although mouse and human Cripto
      have been shown to activate the ras/raf/MAP kinase pathway in mammary epithelial
      cell lines, genetic evidence in Zebrafish has been provided for a relationship
      between the EGF-CFC proteins and Nodal, a member of the transforming growth
      factor family. Here we review the biological role of cripto in development and
      differentiation, pointing out recent findings on the biochemical interactions of
      Cripto, Nodal and Activin-like receptors.

PMID- 11992721
TI  - Chordin-like CR domains and the regulation of evolutionarily conserved
      extracellular signaling systems.
AB  - In fruit flies as well as in humans the Short gastrulation (Sog)/Chordin protein
      functions as an antagonist of the signaling of decapentaplegic (Dpp)/bone
      morphogenetic protein (BMP) in the extracellular space. Such antagonism inhibits
      Dpp/BMP signaling by blocking its binding to the receptor. Modulation of Dpp/BMP
      signaling is phylogenetically conserved and is a key step for the establishment
      of the dorso-ventral axis in vertebrates and invertebrates. Molecular studies
      have shown that the inhibitory activity of Chordin on BMP resides in specific
      cysteine-rich (CR) domains. Interestingly, Chordin-like CR domains are present in
      a growing number of extracellular proteins, several of which appear to be
      involved in BMP signaling regulation. We review here the conservation of the
      Chordin and Sog proteins, and in particular their functional domain, the CR
      domain. We discuss how the study of CR domains may provide a general mechanism
      for the regulation of growth factor signaling in the extracellular space.

PMID- 11992722
TI  - The involvement of a conserved family of RNA binding proteins in embryonic
      development and carcinogenesis.
AB  - Vg1 RBP is a member of a family of highly conserved proteins that appear to be
      involved in RNA localization, stability, and/or translational control in a wide
      variety of cell types and organisms. Over the last few years, the human homologs
      of these proteins have been found to be overexpressed in an increasing number of
      different kinds of cancers. Although the role of these proteins in neoplasia is
      not understood, results from several labs, including our own, are beginning to
      suggest that many of these proteins may be important in cell motility, a
      necessary requirement for metastasis. This paper will review these data and
      suggest a model for the role of Vg1 RBP and its homologs in embryonic development
      and carcinogenesis.

PMID- 11992723
TI  - Tracheal development in Drosophila melanogaster as a model system for studying
      the development of a branched organ.
AB  - The development of the tracheal system of Drosophila melanogaster represents a
      paradigm for studying the molecular mechanisms involved in the formation of a
      branched tubular network. Tracheogenesis has been characterized at the
      morphological, cellular and genetic level and a series of successive, but linked
      events have been described as the basis for the formation of the complex network
      of tubules which extend over the entire organism. Tracheal cells stop to divide
      early in the process of tracheogenesis and the formation of the interconnected
      network requires highly controlled cell migration events and cell shape changes.
      A number of genes involved in these two processes have been identified but in
      order to obtain a more complete view of branching morphogenesis, many more genes
      carrying essential functions have to be isolated and characterized. Here, we
      provide a progress report on our attempts to identify further genes expressed in
      the tracheal system. We show that empty spiracles (ems), a head gap gene, is
      required for the formation of a specific tracheal branch, the visceral branch. We
      also identified a Sulfotransferase and a Multiple Inositol Polyphosphate
      phosphatase that are strongly upregulated in tracheal cells and discuss their
      possible involvement in tracheal development.

PMID- 11992724
TI  - Genetic network of the eye in Platyhelminthes: expression and functional analysis
      of some players during planarian regeneration.
AB  - Planarians are the free-living members (order Tricladida) of the phylum
      Platyhelminthes. They are triploblastic, acoelomate, unsegmented and located at
      the base of the Lophotrochozoa clade. Besides their huge regenerative capacity,
      planarians have simple eyes, considered similar to the prototypic eye suggested
      by Charles Darwin in his book 'On the Origin of Species'. The conserved genetic
      network that determines the initial steps of eye development across metazoans
      supports a monophyletic origin of the various eye types present in the animal
      kingdom. Here we summarise the pattern of expression of certain genes involved in
      the eye network that have been isolated in planarians, such as Otx, Pax-6, Six,
      Rax and opsin. We describe the effects of RNA interference-mediated loss of
      function on eye regeneration. Finally, we discuss the relevance of these findings
      for the evolution of the eye gene network.

PMID- 11992725
TI  - Functional characterization of Ets-binding sites in the sea urchin embryo: three
      base pair conversions redirect expression from mesoderm to ectoderm and endoderm.
AB  - Because of the limited knowledge of target genes for the ets family of
      transcription factors, it is yet unclear how specificity of biological function
      among different members is achieved in this class of proteins. In the present
      study, we compared two Ets-binding sites in two differentially expressed genes of
      the sea urchin embryo. The first gene examined is the cytoskeletal actin CyIIa,
      which is transiently expressed in skeletogenic and secondary mesenchyme and in
      its terminal and permanent phase in the gut. The second one encodes the hatching
      enzyme gene of Strongylocentrotus purpuratus, and is regulated cell-autonomously
      and asymmetrically along the maternally determined animal-vegetal axis. The Ets
      sites within the regulatory regions of these two genes interact and form
      different binding complexes with proteins present in the nuclei of mesenchyme
      blastula embryos. We also demonstrated that the DNA binding specificity of the
      CyIIa Ets-binding site can be converted to the other type of Ets site, as in the
      hatching enzyme promoter, by changing only three base pairs near the Ets core
      sequence. Switching of these three base pairs near the central GGA trinucleotide
      motif characteristic of all Ets-binding targets was also sufficient to redirect
      expression of a reporter gene construct containing a heterologous basal promoter
      from mesenchyme to non-mesenchyme cell type in transgenic sea urchin embryos.
      These observations suggest that binding affinity of ets transcription factors
      plays an important role in determining cell type-specific gene expression.

PMID- 11992726
TI  - Ciona intestinalis cDNA projects: expressed sequence tag analyses and gene
      expression profiles during embryogenesis.
AB  - Ascidians are primitive chordates. Their fertilized egg develops quickly into a
      tadpole-type larva, which consists of a small number but distinct types of cells,
      including those of epidermis, central nervous system with two sensory organs,
      endoderm and mesenchyme in the trunk, and notochord and muscle in the tail. This
      configuration of the ascidian tadpole is thought to represent the most simplified
      and primitive chordate body plan. In addition, the free-swimming and non-feeding
      larvae metamorphose into sessile and filter-feeding adults. The genome size of
      Ciona intestinalis is estimated to be about 160 Mb, and the number of genes
      approximately 15,500. The present Ciona cDNA projects focused on gene expression
      profiles of fertilized eggs, 32-110-cell stage embryos, tailbud embryos, larvae,
      and young adults. Expressed sequence tags (ESTs) of the 5'-most end and 3'-most
      end of more than 3000 clones were determined at each developmental stage, and the
      clones were categorized into independent clusters using the 3'-end sequences.
      Nearly 1000 clusters of them were then analyzed in detail of their sequences
      against a BLASTX search. This analysis demonstrates that, on average, half of the
      clusters showed proteins with sequence similarities to known proteins and the
      other half did not show sequence similarities to known proteins. Genes with
      sequence similarities were further categorized into three major subclasses,
      depending on their functions. Furthermore, the expression profiles of all of the
      clusters were analyzed by whole-mount in situ hybridization. This analysis
      highlights gene expression patterns characteristic to each developmental stage.
      As a result, the present study provides many new molecular markers for each of
      the tissues and/or organs that constitutes the Ciona tailbud embryo. This
      sequence information will be used for further comparative genome studies to
      explore molecular mechanisms involved in the formation of one of the most
      primitive chordate body plans. All of the data fully characterized may be viewed
      at the web site http://ghost.zool.kyoto-u.ac.jp.

PMID- 11992727
TI  - Role of PCNA and ependymal cells in ascidian neural development.
AB  - The central nervous system (CNS) of the ascidian tadpole larva consists of only
      370 cells, yet it develops similarly to the elaborate vertebrate CNS. There are
      two phases in ascidian CNS development: an early phase, in which cells of mixed
      neuronal and non-neuronal (ependymal) fates are formed, and a late phase, in
      which only additional ependymal cells are produced. Proliferating cell nuclear
      antigen (PCNA), the auxiliary factor for DNA polymerase , is expressed
      zygotically in the developing CNS. Here we employ antisense oligonucleotides
      directed against PCNA mRNA to determine the role of late dividing ependymal cells
      in embryos of the ascidian Styela clava. An antisense oligonucleotide beginning
      at the translation start site in PCNA mRNA was effective in inhibiting zygotic
      PCNA accumulation. In normal tadpoles, the head is located in the same
      anteroposterior plane as the tail, which promotes larval swimming and dispersal.
      Embryos treated with PCNA antisense oligonucleotides developed into boomerang
      shaped tadpoles with their heads positioned at an acute angle with respect to
      their tails, causing them to swim in circles rather than in the usual forward
      direction. Further studies showed that PCNA inhibition arrested DNA synthesis and
      induced nuclear DNA fragmentation typical of programmed cell death in the
      developing CNS. No other defects were apparent in these abnormal tadpoles, and
      they were eventually able to metamorphose into juveniles. The results suggest
      that PCNA and late dividing ependymal cells are required for normal CNS
      development and larval morphogenesis in ascidians.

PMID- 11992728
TI  - Pitx genes in Tunicates provide new molecular insight into the evolutionary
      origin of pituitary.
AB  - We have initiated a project aimed at documenting molecular and cellular changes
      underlying the emergence of the hypothalamo-hypophyseal axis in Chordates.
      Considering the phylogenetic position of Tunicates and the 'pan-hypophyseal'
      expression pattern of Pitx genes in Vertebrate pituitary, we searched for a Pitx
      related homeobox gene in the ascidian Ciona intestinalis, and identified Ci-Pitx
      (ona intestinalis uitary homeobo gene). We also isolated Cs-Pitx and Bs-Pitx, the
      Ci-Pitx respective counterparts of Ciona savignyi and Botryllus schlosseri, two
      other Tunicate species. Ci-Pitx mRNA encodes a putative protein exhibiting the
      diagnostic K50-Paired-class homeodomain and a conserved C-terminal Aristaless
      domain. Embryonic expression pattern of Ci-Pitx revealed a conserved expression
      domain in the anterior neural ridge and subsequently in the pharyngeal
      primordium, defined in Vertebrates as the stomodeal ectomere, which encompasses
      the presumptive pituitary territory. This shows that expression at early steps of
      pituitary development is a feature of Pitx-related genes that was already present
      in the last common ancestor of Chordates.

PMID- 11992729
TI  - Cititf1 and endoderm differentiation in Ciona intestinalis.
AB  - Studies on the initial formation of the endoderm have lead to the identification,
      mostly in Xenopus, of numerous genes relevant for the formation of this tissue
      during early embryogenesis (reviewed by Date, Curr. Biol. 9 (1999) R812-R815 and
      by Yasuo and Lemaire, Curr. Biol. 9 (1999) 869-879). In ascidians, the most
      primitive chordates, endoderm differentiation is an autonomous process which is
      almost complete at 64 cells stage. Cititf1, a gene homologous to mammalian Titf1,
      is the first specific endodermal marker isolated from the ascidian Ciona
      intestinalis (Ristatore et al., Development 126 (1999) 5149-5159). Here we study
      the in vivo role of Cititf1 by using two different approaches: interference and
      ectopic expression. The results presented here show that interference with
      Cititf1 function seems to affect gastrulation movements, while ectopic expression
      of Cititf1 mRNA into the notochord alters differentiation of this tissue probably
      by recruiting notochord blastomeres to an endodermal fate. These data together
      with studies, still in progress in our laboratory, on the transcriptional
      regulation of Cititf1, strongly indicate that Cititf1 plays an important role in
      the process of endoderm formation in Ciona embryogenesis.

PMID- 11992730
TI  - Gene duplications in the prototypical cephalochordate amphioxus.
AB  - The new discipline of Evolutionary Developmental Biology (Evo-Devo) is facing the
      fascinating paradox of explaining morphological evolution using conserved pieces
      or genes to build divergent animals. The cephalochordate amphioxus is the closest
      living relative to the vertebrates, with a simple, chordate body plan, and a
      genome directly descended from the ancestor prior to the genome-wide duplications
      that occurred close to the origin of vertebrates. Amphioxus morphology may have
      remained relatively invariant since the divergence from the vertebrate lineage,
      but the amphioxus genome has not escaped evolution. We report the isolation of a
      second Emx gene (AmphiEmxB) arising from an independent duplication in the
      amphioxus genome. We also argue that a tandem duplication probably occurred in
      the Posterior part of the Hox cluster in amphioxus, giving rise to AmphiHox14,
      and discuss the structure of the chordate and vertebrate ancestral clusters.
      Also, a tandem duplication of Evx in the amphioxus lineage produced a
      prototypical Evx gene (AmphiEvxA) and a divergent gene (AmphiEvxB), no longer
      involved in typical Evx functions. These examples of specific gene duplications
      in amphioxus, and other previously reported duplications summarized here,
      emphasize the fact that amphioxus is not the ancestor of the vertebrates but
      'only' the closest living relative to the ancestor, with a mix of prototypical
      and amphioxus-specific features in its genome.

PMID- 11992731
TI  - Conservation of Pax gene expression in ectodermal placodes of the lamprey.
AB  - Ectodermal placodes contribute to the cranial ganglia and sense organs of the
      head and, together with neural crest cells, represent defining features of the
      vertebrate embryo. The identity of different placodes appears to be specified in
      part by the expression of different Pax genes, with Pax-3/7 class genes being
      expressed in the trigeminal placode of mice, chick, frogs and fish, and Pax-2/5/8
      class genes expressed in the otic placode. Here, we present the cloning and
      expression pattern of lamprey Pax-7 and Pax-2, which mark the trigeminal and otic
      placodes, respectively, as well as other structures characteristic of vertebrate
      Pax genes. These results suggest conservation of Pax genes and placodal
      structures in basal and derived vertebrates.

PMID- 11992732
TI  - CP27 function is necessary for cell survival and differentiation during tooth
      morphogenesis in organ culture.

PMID- 11992733
TI  - Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene
      in human subjects.
AB  - Musk ambrette, musk ketone and musk xylene have a long history of use as
      fragrance ingredients, although musk ambrette is no longer used in fragrances. As
      part of the review of the safety of these uses, it is important to consider the
      systemic exposure that results from these uses. Since the primary route of
      exposure to fragrances is on the skin, dermal doses of carbon-14 labelled musk
      ambrette, musk ketone and musk xylene were applied to the backs (100 cm2) of
      healthy human volunteers (two to three subjects) at a nominal dose level of 10-20
      microg/cm2 and excess material removed at 6 h. Means of 2.0% musk ambrette, 0.5%
      musk ketone and 0.3% musk xylene were absorbed based on the amounts excreted in
      urine and faeces during 5 days. Most of the material was excreted in the urine
      with less than 10% of the amount excreted being found in faeces. No radioactivity
      was detected in any plasma sample, consistent with low absorption, and no
      radioactivity was detected (<0.02% dose) in skin strips taken at 120 h. Analysis
      of urine samples indicated that all three compounds were excreted mainly as
      single glucuronide conjugates. The aglycones were chromatographically different,
      but of similar polarity, to the major rat metabolites excreted in bile also as
      glucuronides.

PMID- 11992734
TI  - Altholactone, a novel styryl-lactone induces apoptosis via oxidative stress in
      human HL-60 leukemia cells.
AB  - Plant styryl-lactone derivatives isolated from Goniothalamus sp. are potential
      compounds for cancer chemotherapy. In this study, we have examined the mechanisms
      of apoptosis induced by altholactone, a stryl-lactone isolated from the Malaysian
      plant G. malayanus on human HL-60 promyelocytic leukemia cells. Flow cytometric
      analysis of the externalization of phosphatidylserine (PS) using the annexin V/PI
      method on altholactone treated HL-60 cells showed a concentration-dependent
      increase of apoptosis from concentrations ranging from 10.8 (2.5 microg/ml) to
      172.4 microM (40 microg/ml). Pre-treatment with the antioxidant N-acetylcysteine
      (1 mM) completely abrogated apoptosis induced by altholactone, suggesting for the
      involvement of oxidative stress. Further flow cytometric assessment of the level
      of intracellular peroxides using the fluorescent probe 2',7'-dichlorofluorescein
      diacetate (DCFH-DA) confirmed that altholactone induced an increase in cellular
      oxidative stress in HL-60 cells which was suppressed by N-acetylcysteine. In
      summary, our results demonstrate for the first time that altholactone induced
      apoptosis in HL-60 cells occurs via oxidative stress.

PMID- 11992735
TI  - Use of Haber's Rule to estimate the risk of diabetes from background exposures to
      dioxin-like compounds.
AB  - Recent publications have reported a weak but consistent correlation between
      diabetes incidence and occupational or accidental exposure to dioxins. As with
      most work involving environmental xenobiotics, these studies suffered from the
      analytical problem that the reference populations had some degree of exposure. We
      have used Haber's Rule to relate the integrated exposure of subjects involved in
      an industrial exposure to dioxins, reported by Sweeney et al. [Teratog. Carcinog.
      Mutagen. 17 (1998) 241], to the incremental probability of diabetes incidence. We
      estimated that background exposure to dioxin-like compounds by the referents
      contributed <1% of their diabetes risk, suggesting that background exposure to
      dioxins is not a significant risk factor for individuals who have not been
      occupationally or accidentally exposed.

PMID- 11992736
TI  - Diclofenac activates T cells in the direct popliteal lymph node assay and
      selectively induces IgG(1) and IgE against co-injected TNP-OVA.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently associated with
      immune-mediated hypersensitivity reactions. The NSAID diclofenac is associated
      with several distinct allergic and autoimmune-like reactions including
      anaphylaxis, idiosyncratic hepatotoxicity and autoimmune hemolytic anemia. The
      aim of this study was to examine the immunostimulating potential of diclofenac in
      the direct popliteal lymph node assay (PLNA) and reporter antigen PLNA. In BALB/c
      mice, diclofenac caused dose-dependent increases in PLN weight and PLN
      cellularity in the direct PLNA; 0.25 mg was non-immunostimulating whereas 0.50
      1.00 mg caused a significant PLN reaction. In the direct PLNA, diclofenac also
      increased the percent of T cells in the PLN with activated phenotypes
      (CD44(high)CD62L(low) and CD44(high)CD62L(high)). Finally, the magnitude of the
      diclofenac-induced direct PLN reaction was significantly reduced when the assay
      was conducted in T-cell-deficient mice. When co-injected with the reporter
      antigen TNP-Ficoll (trinitrophenyl Ficoll), 0.50 mg diclofenac caused significant
      increases in PLN weight, PLN cellularity, and induced IgM and IgG(1) anti-TNP
      antibody forming cells (AFCs) in the PLN. In a final set of studies, a TNP-OVA
      PLNA was conducted using diclofenac, phenobarbital (negative control) and
      streptozotocin (positive control). As expected, phenobarbital (1.00 mg) failed to
      cause an increase in PLN cellularity or induce AFCs in the PLN. Streptozotocin
      (1.00 mg) caused significant increases in PLN cellularity, IgM AFCs, and
      selectively induced IgG(2a) and IgG(2b) AFCs against TNP-OVA. Likewise,
      diclofenac caused dose-dependent increases (0.25-1.00 mg) in PLN cellularity and
      IgM AFCs. However, in contrast to streptozotocin, diclofenac caused a selective
      dose-dependent increase in both IgG(1) and IgE AFCs. Finally, an increase in the
      intracellular level of IL-4, but not INFgamma, was detected in CD4(+) PLN cells
      following the injection of diclofenac mixed with TNP-OVA. Collectively, these
      data suggest that diclofenac: (i) induces a T-cell-dependent direct PLN reaction
      that; (ii) provides non-cognate help for IgG AFC production when co-injected with
      TNP-Ficoll, possibly through the formation of neo-antigens; and (iii) possesses
      intrinsic adjuvant activity that selectively induces IL-4 mediated production of
      IgG(1) and IgE against co-injected TNP-OVA.

PMID- 11992737
TI  - Bilirubin/biliverdin-Cu(II) induced DNA breakage; reaction mechanism and
      biological significance.
AB  - Bilirubin and its metabolic precursor biliverdin are heme degradation products
      but have been proposed as physiological antioxidants. Reports from another
      laboratory as well as from ours have shown bilirubin to form a complex with the
      transition metal ion-Cu(II). Such a complex was shown by us to cause oxidative
      DNA damage. Further, biliverdin was also shown to be capable of causing similar
      DNA damage. In the present studies we have aimed to elucidate the mechanism of
      DNA breakage reaction by these bile pigments. Absorption and fluorescence studies
      indicate binding of bile pigments to DNA and copper ions. Cu(II) is reduced by
      these compounds to Cu(I) which is an essential intermediate in the DNA breakage
      reaction. Redox recycling of Cu(II) leads to generation of reactive oxygen
      species. Strand scission by the bile pigments-Cu(II) system is found to be
      biologically significant as assayed by bacteriophage inactivation. Our results,
      therefore are suggestive of one of the mechanisms through which endogenous DNA
      damage may occur.

PMID- 11992738
TI  - Induction of oxidative stress in paraquat formulating workers.
AB  - Paraquat as a bipyridyl compound is widely used as an effective herbicide
      worldwide. In this study, oxidative stress was investigated in blood samples of
      workers in a pesticide factory, formulating paraquat products for use in
      agriculture. Controls were age-matched workers with no history of pesticide
      exposure. They were measured for lipid peroxidation (LPO), antioxidant power and
      total thiol (SH) groups in blood. The results expressed as mean+/-SD show
      induction of oxidative stress in workers as revealed by increased plasma LPO
      (11.46+/-0.99 vs 10.11+/-0.69, P<0.001), decreased plasma antioxidant capacity
      (1.35+/-0.03 vs 1.54+/-0.05, P<0.001) and plasma SH groups (0.16+/-0.01 vs 0.21+/
      0.01, P<0.001) in comparison to those of controls. It is concluded that paraquat
      formulating factory workers have elevated LPO and decreased antioxidant power,
      which may put them in further consequences of oxidative stress.

PMID- 11992739
TI  - A histopathologic study of the nervous system after inhalation exposure of 1
      bromopropane in rat.
AB  - 1-Bromopropane (1-BP) has recently become known as an alternative cleaning
      material with less damage to the ozone layer. However, its toxicity is not fully
      evaluated. This study was designed to investigate the repeated inhalation
      toxicity of 1-BP on the nervous systems in Sprague-Dawley rats. The experiment
      was done by repeated exposure of the rats to 0, 200, 500, and 1250 ppm for 6 h
      per day, 5 days a week, for 13 weeks, respectively. Morphologic studies were done
      for the central nervous system, sacral and peroneal nerves. The serial sections
      of the brain and spinal cord of 1-BP inhalation groups revealed no pathological
      features either in the gray or white matter. The nerve fiber teasing, light and
      electron microscopic studies of the sacral and peroneal nerve fibers showed no
      significant difference between 1-BP inhalation groups and the control group. From
      these results, it is concluded that the nervous system is histologically
      resistant to the repeated inhalation of 1-BP up to 1250 ppm for 13 weeks.
      Experiments with higher concentrations of 1-BP and the functional studies are
      necessary to clarify the 1-BP toxicity.

PMID- 11992740
TI  - Tellurium-induced cognitive deficits in rats are related to neuropathological
      changes in the central nervous system.
AB  - The effects of sodium tellurite 0.1 and 0.4 mg/kg were assessed in the Morris
      water maze. Two days after treatment rats were tested for acquisition
      (posttreatment days 3-6) and on seventh day on a spatial retention task.
      Tellurium treatment was found to cause significant impairment in retention of the
      spatial learning task. Locomotor disturbances were not the cause of the observed
      effects. Ultrastructural observations showed neuropathological changes in
      hippocampus subfields and prefrontal cortex with swelling of synapses, astrocytes
      and astrocytic processes around the vessels in the cerebral cortex neuropil.
      Severity of the observed changes in glial-neuronal unit was in correlation with
      the extent of learning impairment. A direct injury of Schwann cells with the
      secondary myoclasis was noted in the sciatic nerve. Our results indicate that
      acute treatment with sodium tellurite results in impairment of learning and
      spatial memory.

PMID- 11992741
TI  - The effects of ebselen on cisplatin and diethyldithiocarbamate (DDC) cytotoxicity
      in rat hippocampal astrocytes.
AB  - Ebselen is a seleno-organic compound with documented cytoprotective properties.
      Little work has been done, however, demonstrating ebselen's cytoprotective
      properties in neural cell lines. In order to examine the effects of this compound
      and its mechanism of action, astrocytes were exposed to two known neurotoxicants,
      cisplatin and diethyldithiocarbamate (DDC). Cells were pretreated with 30 microM
      ebselen and subsequently treated with either 150 microM DDC for 1 h or 250 and
      500 microM cisplatin for 24 h. Results indicate significant increases in
      viability in cells pretreated with ebselen and exposed to cisplatin. Ebselen
      pretreatment did not significantly increase viability in cells exposed to DDC.
      Light and scanning electron microscopy studies confirm the viability studies.
      Gross morphological damage was seen in cells treated with cisplatin, however,
      cells pretreated with ebselen and then exposed to cisplatin, appeared similar to
      controls. No differences were noted in cells pretreated with ebselen and then
      exposed to DDC or cells treated with DDC alone. In order to examine the mechanism
      of protection of this compound, glutathione status was examined. Results show
      that ebselen does not significantly increase reduced or oxidized glutathione
      (GSH, GSSG). All cell groups treated with cisplatin showed an increase in GSH
      levels. Ebselen showed protection in glutathione depleted cells at the 250 microM
      cisplatin dose. DDC treatment showed no significant increase in either reduced or
      oxidized glutathione. We conclude that ebselen significantly protects against
      cisplatin, but not DDC toxicity. We further conclude that this protection is not
      related to changes in glutathione status in the rat hippocampal cell line as has
      been reported in other cell types.

PMID- 11992742
TI  - The promise of coxibs: how far have we progressed?

PMID- 11992743
TI  - Gastrointestinal safety of coxibs and outcomes studies: what's the verdict?
AB  - Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, their
      main limitation is gastrointestinal (GI) injury. Two double-blind, randomized,
      outcomes trials were conducted to determine the incidence of clinical GI events
      with the coxibs, rofecoxib and celecoxib, compared with nonselective NSAIDs. The
      VIGOR study (VIOXX Gastrointestinal Outcomes Research) compared rofecoxib with
      naproxen, and the CLASS study (Celecoxib Long-term Arthritis Safety Study)
      compared celecoxib with ibuprofen and diclofenac. The VIGOR trial revealed a
      relative risk reduction for clinical upper GI events of 50% with rofecoxib, and a
      60% reduction in complicated events. In the CLASS study, the 23% reduction in
      complicated ulcers with celecoxib did not reach statistical significance (P =
      0.45), although when all clinical events were examined, the 34% reduction was
      significant (P = 0.04). However, low-dose aspirin use, which was allowed in the
      CLASS study, may have influenced the results. A subgroup analysis in the patients
      who did not take aspirin revealed a nonsignificant 45% reduction in complicated
      events with celecoxib (P = 0.19), and a 47% reduction in complicated and
      symptomatic ulcers (P = 0.02).

PMID- 11992745
TI  - Renal effects of cyclooxygyenase-2-selective inhibitors.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used. These agents are
      associated with adverse renal effects caused by the reduction in synthesis of
      renal prostaglandins through inhibition of cyclooxygenase (COX). Both isoforms of
      COX, COX-1 and COX-2, are expressed in the kidney in constitutive and inducible
      forms. It is assumed therefore that the COX-2-selective inhibitors, rofecoxib and
      celecoxib, would have an effect on renal function similar to that of nonselective
      NSAIDs. Several studies have evaluated this issue, although they have different
      study models and some have design flaws that limit their interpretation.
      Therefore, conclusions should be based on the pattern of observed effects rather
      than on individual data. These studies suggest that both celecoxib and rofecoxib
      can cause sodium retention and decrease glomerular filtration rate (GFR) to a
      similar extent as nonselective NSAIDs in patients at risk for adverse renal
      effects. Consequently, the same precautions regarding renal risk that are
      followed for nonselective NSAIDs should be used when selective COX-2 inhibitors
      are administered.

PMID- 11992747
TI  - Update of ACR guidelines for osteoarthritis: role of the coxibs.
AB  - The American College of Rheumatology (ACR) recently provided an update to the
      guidelines published in 1995 on the management of osteoarthritis (OA) of the knee
      and hip. Members of the Ad Hoc Committee on OA Guidelines followed an evidence
      based medicine approach to revise the guidelines by reviewing an extensive
      literature search of the Cochrane and Medline databases and published abstracts,
      and discussing evidence with expert rheumatologists. The goal of the guidelines
      is to provide recommendations to control patients' OA pain, improve function and
      health-related quality of life, and avoid therapeutic toxicity. As in the
      original guidelines, nonpharmacologic interventions involving patient education
      and physical measures are recommended following initial diagnosis of OA. The
      pharmacologic algorithm was updated to include currently available therapeutic
      agents. Acetaminophen remains first-line therapy because of its cost, efficacy,
      and safety profiles. Cyclooxygenase-2-selective inhibitors (coxibs) have been
      included as an alternative to nonselective nonsteroidal anti-inflammatory drugs
      (NSAIDs) in patients at risk for upper gastrointestinal adverse events. Tramadol
      is an available alternative for patients who have a contraindication to coxibs or
      nonselective NSAIDs or for those who have not responded to previous oral therapy.
      Intra-articular injections or topical therapy may be used as monotherapy, or as
      an adjunct to oral analgesia. Surgical treatment of OA remains a last resort for
      patients who have failed to respond to nonpharmacologic and pharmacologic
      treatment approaches, and have progressive limitation in their activities of
      daily living. Several therapies for the prevention or treatment of OA are
      currently under investigation, including nutritional supplements, such as
      glucosamine and chondroitin, disease-modifying OA drugs, and devices, such as
      acupuncture and electromagnetic therapy. It is anticipated that the guidelines
      for the management of OA will continue to evolve as new therapies become
      available.

PMID- 11992749
TI  - Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a worldwide problem that affects 5 million people in
      the United States alone. Until the approval of tacrine in the mid-1990s, there
      was no effective therapy for the cognitive symptoms of AD. Although cholinergic
      therapy provides modest but significant symptomatic relief, the development of
      effective disease-modifying therapy is essential. It has been demonstrated that a
      number of inflammatory processes are active in the brain of patients with AD, and
      therefore it is believed that an anti-inflammatory regimen may offer some degree
      of neuroprotection. Several studies have indicated that use of nonsteroidal anti
      inflammatory drugs (NSAIDs) is associated with delayed onset and/or slowed
      cognitive decline in AD. Although not currently approved for this condition,
      recent findings have demonstrated that cyclooxygenase (COX)-2 is of primary
      importance in the inflammatory response and may have a role in neurodegeneration.
      Therefore, selective COX-2 inhibitors (coxibs) may have an advantage over
      traditional NSAIDs as potential therapeutic agents in AD. The Alzheimer's Disease
      Cooperative Study (ADCS) is conducting an ongoing multicenter, double-blind,
      placebo-controlled trial to determine whether rofecoxib, a coxib, or naproxen, a
      nonselective NSAID, will slow the rate of cognitive and clinical decline in AD.
      This study, along with other clinical studies currently under way, will determine
      the utility of selective and nonselective COX inhibitors for the prevention and
      treatment of AD.

PMID- 11992750
TI  - Screening for colon cancer and evaluation of chemoprevention with coxibs.
AB  - Although colorectal cancer is one of the most preventable forms of visceral
      cancer, it remains the second leading cause of cancer death in the United States.
      Most colorectal cancers are believed to arise from adenomatous polyps,
      premalignant mucosal masses that account for up to two thirds of colorectal
      polyps. Early identification and removal of adenomas prevent the development of
      colorectal cancer. Colonoscopy has emerged as the dominant method for evaluating
      symptomatic patients with colorectal cancer and for surveillance of patients with
      previous colon polyps or cancer. In the United States, fecal occult blood testing
      and flexible sigmoidoscopy are the most commonly used screening methods in
      average-risk persons, although there is an emerging trend toward the use of
      colonoscopy. For both screening and surveillance, the type of screening test used
      and the intervals at which it is performed are based on risk stratification,
      which also serves as the basis for selecting potential candidates for
      chemoprevention. Because colonoscopy, like most screening procedures, has several
      disadvantages, including risk of perforation and bleeding and an inherent "miss
      rate," alternative methods of prevention are being explored. A variety of agents
      with potential chemopreventive benefits have been identified, including
      cyclooxygenase (COX)-2-specific inhibitors (coxibs) even though these agents have
      not been approved for this use in the United States. COX-2 is overexpressed in
      colonic adenomas and cancers, and its inhibition has been shown to produce
      regression of polyps in familial adenomatous polyposis. Nonselective COX
      inhibition with nonsteroidal anti-inflammatory drugs (NSAIDs) has been
      consistently associated with reductions in the risk of mortality and the
      incidence of colorectal adenomas and cancers in case-control studies. Thus,
      selective COX-2 inhibition is a potential method of risk reduction in high-risk
      screening and surveillance groups, and large-scale trials of coxibs for the
      prevention of recurrence of adenomas after polypectomy are currently underway.

PMID- 11992752
TI  - Methylphenidate treatment.
AB  - Methylphenidate is the psychotropic drug most commonly used to treat individuals
      suffering from developmental attention-deficit-hyperactivity disorder. Additional
      attention deficit is part of numerous neurologic diseases in childhood. Despite
      the vast extent of scientific research on methylphenidate, the use of this
      stimulant in the treatment of cognitive and behavioral dysfunction in children
      with epilepsy, brain tumor, leukemia, closed brain injury, encephalitis,
      meningitis, or mental retardation continues to be controversial. Only few data
      exist about the efficacy and side effects of methylphenidate treatment in
      children with this neurologic illness or history. The aim of the present study is
      to provide a review of this important clinical topic and perhaps to stimulate
      further controlled investigations.

PMID- 11992753
TI  - Phenotypic spectrum of Salla disease, a free sialic acid storage disorder.
AB  - Salla disease (MIM 269920) represents the mildest phenotype among recessively
      inherited lysosomal-free sialic acid storage disorders. Although the vast
      majority of Salla disease patients in Finland share the same founder mutation,
      R39C in the SLC17A5 gene, there still is a wide clinical variation among mentally
      retarded, ataxic patients. We evaluated neurologic and neurocognitive findings of
      Salla disease in a cross-sectional study of 41 Finnish patients who were 11
      months to 63 years of age (median = 19.5 years). The phenotype of Salla disease
      could be classified into two main categories. The majority of patients (90%) had
      so-called conventional phenotype, including a subgroup of seven patients with
      relatively mild symptoms. All but two patients with conventional phenotype were
      homozygous for the Finnish founder mutation. Four severely disabled, profoundly
      mentally retarded patients, 15-28 years of age, clearly could be clinically
      delineated as a separate group, likely reflecting the underlying compound
      heterozygous genotype. A typical developmental pattern could be outlined in the
      conventional type of the disease, emphasizing a strong motor handicap in Salla
      disease. The cognitive profile consisted of better verbal ability, especially
      speech comprehension, compared with nonverbal functioning in all patients. Our
      results indicate a partial genotype-phenotype correlation, although factors other
      than the molecular background are also involved in the phenotypic manifestation
      of Salla disease.

PMID- 11992754
TI  - Diffusion-weighted images in neonatal cerebral hypoxic-ischemic injury.
AB  - Diffusion-weighted images of magnetic resonance imaging, obtained by mapping
      apparent diffusion coefficients, are more sensitive than other magnetic resonance
      imaging sequences in the earliest detection of acute cytotoxic injury. The
      usefulness of diffusion-weighted images in focal ischemic brain injury has been
      documented in children and adults. We report eight full-term neonates with global
      cerebral hypoxic-ischemic injury and abnormalities on diffusion-weighted images.
      Distribution of diffusion-weighted imaging abnormalities in the eight neonates
      was consistent with global hypoxic-ischemic injury in full-term neonates, with
      diffuse cortical necrosis, border-zone infarcts, or basal ganglia/thalamic
      injury. Magnetic resonance imaging scans with diffusion-weighted images were
      obtained within the first 4 days of age in all eight neonates. In each patient,
      standard magnetic resonance imaging sequences substantially underestimated the
      extent of injury when compared with diffusion-weighted images in unmyelinated
      neonatal brains. Extensive injury bilaterally with basal ganglia and thalamic and
      widespread multifocal cortical injury correlated with a severe neurologic
      outcome. Lesser degrees of injury, limited to smaller sectors of cortical or
      border zone involvement, were associated with better neurologic outcome. The high
      sensitivity of diffusion-weighted images to map the extent of hypoxic-ischemic
      injury in neonates makes it a potentially useful tool for assessing future
      neuroprotective strategies for neonatal hypoxic-ischemic injury.

PMID- 11992755
TI  - Seizure outcome of intractable partial epilepsy in children.
AB  - The intractable partial epilepsy outcome information is important in determining
      not only when epilepsy surgery evaluation should begin but also in deciding who
      would benefit and what is the likelihood of any benefit from surgery. Medical
      records of 50 children diagnosed with nontumor-related partial seizures,
      confirmed by video-electroencephalography (video-EEG), had at least one seizure
      per week and were followed for at least 2 consecutive years after video-EEGs were
      reviewed. There were 30 patients who continued with antiepileptic drug treatment
      after video-EEG. The seizure outcome analysis revealed a significant improvement
      of seizure control in the first year of follow-up but no difference between the
      first year and the following 3 years. Only 30% had excellent long-term outcome
      (seizure free or less than one seizure per 6 months). The presence of focal
      lesions on neuroimaging was the only risk factor of poor outcome. The other 20
      patients underwent epilepsy surgery after video-EEG; 60% attained excellent
      outcome despite the fact that 90% had focal neuroimaging abnormality. Children
      whose partial epilepsy remained intractable after 1 year of antiepileptic drug
      treatment should be evaluated for candidacy of epilepsy surgery, particularly
      those who have focal lesions on neuroimaging.

PMID- 11992756
TI  - The ketogenic diet: a review of the experience at Connecticut Children's Medical
      Center.
AB  - We undertook a retrospective analysis of epilepsy patients referred and treated
      for more than 6 months with the ketogenic diet during 1994-1999 at Connecticut
      Children's Medical Center. Outcome measures included antiepileptic drug number,
      seizure frequency, electroencephalogram background/paroxysmal activity, and
      adverse effects at 6 months and 1 year on the ketogenic diet. The final cohort
      included 24 of 48 referred patients (mean age, 6.5 years; range = 1-15 years of
      age). The etiology of epilepsy was equally divided between idiopathic and
      cryptogenic epilepsy and symptomatic epilepsy. Intention to treat analysis
      revealed that 35% (17 of 48) achieved more than 50% reduction in seizure
      frequency, and 8.5% (four of 48) were seizure-free by 6 months. A sustained 50%
      or greater reduction at 1 year was observed in 23% (11 of 48), and the same 8.5%
      (four of 48) remained seizure-free. None of these improvements were statistically
      related to age (P = 0.97), sex (P = 0.78), or epilepsy etiology (P = 0.80). The
      number of antiepileptic drugs used per patient decreased. Electroencephalogram at
      1 year demonstrated an improvement in background in 31% (five of 16 patients) and
      a reduction in paroxysmal features in 37.5% (6 of 16 patients). Most adverse
      effects were mild, self-limited, and occurred early. Hyperuricemia (more than 6
      mg/dL) was more persistent in three patients.

PMID- 11992757
TI  - Long-term follow-up of children with chronic relapsing polyneuropathy.
AB  - Long-term follow-up of three children with early-onset chronic inflammatory
      demyelinating polyneuropathy is presented. A 3-year-old male (Patient 1)
      manifested initially progressive muscle weakness during 6 months with spontaneous
      regression, followed by two severe relapses at 5 and 6 years of age. Decreased
      arylsulfatase A activity was present in Patient 1 (17.6) and his family members
      (24.1-40 nmol/mg/hour). Arterial hypertension up to 20/12 kPa was present in two
      patients in the initial phase associated with muscle stiffness, occasional
      meningism, and left ventricular hypertrophy in one of them (Patient 3).
      Subsequently, they both developed two mild relapses at 3.5 and 6 years of age.
      Clinical outcome was excellent in all three cases, although clinical course,
      therapy response, and electrophysiologic outcome was quite different in the only
      patient with low arylsulfatase A activity. The significance of this difference is
      discussed.

PMID- 11992758
TI  - Efficacy of intravenous immunoglobulin in Landau-Kleffner syndrome.
AB  - We administered 2 gm/kg of intravenous gamma globulin (IVIG) to each of five
      consecutive patients with Landau-Kleffner syndrome, over 4 days. We compared the
      1-month baseline to that following IVIG using a severity score assessing speech,
      comprehension, behavior, seizures, and electroencephalography. There was a
      significant drop in this score after IVIG (P = 0.025). Two patients had a
      dramatic response to IVIG, with complete resolution of symptoms. This finding
      suggests that IVIG has at least some efficacy for the therapy of Landau-Kleffner
      syndrome.

PMID- 11992759
TI  - Subdural hematoma in term infants.
AB  - Subdural hematomas are uncommon in term infants. The study objectives were to
      evaluate risk factors for and clinical significance of small subdural hematomas
      observed on computerized tomography. During a 3-year period, 26 near-term and
      term nonasphyxiated infants were found to have a subdural hematoma on computed
      tomography. Clinical indications for computed tomography were respiratory
      symptoms in 15 infants and neurologic symptoms in 10 infants; one infant had a
      skull fracture. Subdural hematomas were less than 3-mm maximum transverse
      dimensions in all infants: location was infratentorial (n = 7), supratentorial (n
      = 7), and in both sites (n = 12). Four infants also had evidence of edema and
      hemorrhage within the anterior temporal lobe. Delivery was vaginal in 25 of 26
      infants, and forceps were used in 13 (50%) infants. Twenty-five infants were
      managed expectantly; one infant underwent surgical elevation of a depressed skull
      fracture. No infant required surgical evacuation of the subdural hematoma. At
      discharge, nine infants with subdural hematoma exhibited an abnormal examination,
      i.e., mild hypotonia (n = 7) and Erb's palsy (n = 2). The clinical syndrome
      attributed to subdural hematoma was most often a subtle clinical problem. The
      presence of subdural hematoma documented by computed tomography is not
      necessarily always indicative of birth trauma and may occur as sequelae of an
      otherwise uncomplicated delivery.

PMID- 11992760
TI  - Methotrexate leukoencephalopathy presenting as Kluver-Bucy syndrome and uncinate
      seizures.
AB  - Methotrexate causes several biochemical changes that impact the nervous system.
      The neurotoxicity usually affects the cerebral white matter, causing a
      leukoencephalopathy that can be chronic and progressive with cognitive decline. A
      15-year-old male developed olfactory seizures and behavioral abnormalities
      (hypersexuality, placidity, and memory disturbances) compatible with partial
      Kluver-Bucy syndrome after treatment for central nervous system leukemia with
      intraventricular methotrexate. A magnetic resonance imaging study revealed
      evidence of white matter disease affecting both temporal lobes. A brain biopsy
      revealed a necrotizing encephalopathy compatible with methotrexate-related white
      matter injury. It may be prudent to verify normal cerebrospinal fluid dynamics
      before the administration of intraventricular methotrexate in children with a
      history of central nervous system leukemia.

PMID- 11992761
TI  - Trigeminal neuralgia in children: two case reports.
AB  - Trigeminal neuralgia in children is extremely rare, and current options for the
      management of it are not very well defined. We present here two children with
      trigeminal neuralgia reaching the second branch, one of whom has a true painful
      state and treatment difficulties.

PMID- 11992762
TI  - Syringomyelia presenting as paroxysmal arm posturing resembling seizures.
AB  - A 9-year-old female presented with daily episodes of medically refractory
      paroxysmal bilateral arm posturing, which had long been thought to be epileptic
      seizures. She also had other types of episodes, including daily staring spells
      and infrequent generalized tonic-clonic convulsions. Neurologic examination was
      normal except for delayed cognitive development. The results of previous
      electroencephalograms (EEG) were normal, and magnetic resonance imaging of the
      head revealed a Chiari I malformation. Video EEG monitoring revealed no EEG
      changes during the attacks, and magnetic resonance imaging of the spine revealed
      a large cervical syrinx associated with the Chiari malformation. The episodes of
      paroxysmal bilateral dystonic arm posturing resolved after surgical intervention
      for the syrinx. This report illustrates that cervical cord disease is an unusual
      although potentially treatable condition to be considered in the differential
      diagnosis of paroxysmal episodes with dystonic movements of the arms, even in the
      absence of other physical findings of myelopathy.

PMID- 11992763
TI  - Acute lethal encephalopathy in systemic juvenile rheumatoid arthritis.
AB  - Macrophage activation syndrome is the most common cause of death in children with
      systemic juvenile rheumatoid arthritis. We present a first patient with systemic
      juvenile rheumatoid arthritis in which acute necrotizing encephalopathy developed
      as a complication of macrophage activation syndrome but not of Reye's syndrome.
      The suspected mechanism of this lethal complication is discussed.

PMID- 11992764
TI  - Treatment of dystonia in striatal necrosis caused by Mycoplasma pneumoniae.
AB  - We report on an 8-year-old male with bilateral striatal necrosis secondary to
      Mycoplasma pneumoniae respiratory infection. This patient has been remarkable for
      persistent severe dystonia that has been difficult to treat. We share our
      experience of beneficial responses to multimodal treatment, including moderate
      doses of trihexyphenidyl, botulinum toxin, and intrathecal baclofen.

PMID- 11992765
TI  - Pediatric meralgia paresthetica.
AB  - Meralgia paresthetica is a focal peripheral neuropathy involving the lateral
      femoral cutaneous nerve and is rarely observed in pediatric practice. Previous
      reports have highlighted its occurrence within the context of a regional bony
      malignancy. We present here three patients less than 18 years of age with
      idiopathic meralgia paresthetica.

PMID- 11992766
TI  - Intracranial calcification, retinopathy, and osteopenia: a new syndrome?
AB  - We describe two brothers with bilateral exudative retinopathy, intracranial
      calcifications, a sclerotic bony disorder, and normal intelligence. The younger
      brother also has osteopenia, mild splenomegaly, and pancytopenia. We review the
      literature with emphasis on the unique features of these patients.

PMID- 11992767
TI  - Cyclosporine A neurotoxicity in a patient with idiopathic renal magnesium
      wasting.

PMID- 11992769
TI  - Design and synthesis of a piperazinylalkylisoxazole library for subtype selective
      dopamine receptor ligands.
AB  - A piperazinylbutylisoxazole libary was designed, synthesized and screened for the
      binding affinities to dopamine D2, D3, and D4 receptors. Several ligands were
      identified to possess high binding affinity and selectivity for the D3 and D4
      receptors over the D2 receptor. Compounds 6s and 6t showed K(i) values of 2.6 nM
      and 3.9 nM for the D3 receptor with 46- and 50-fold selectivity over the D2
      receptor, respectively.

PMID- 11992770
TI  - Structure-based optimisation of 2-aminobenzylstatine derivatives: potent and
      selective inhibitors of the chymotrypsin-like activity of the human 20S
      proteasome.
AB  - We have identified 2-aminobenzylstatine derivatives that inhibit non-covalently
      the chymotrypsin-like activity of the human 20S proteasome. A structure-based
      optimisation approach has allowed us to improve the potency of this structural
      class of proteasome inhibitors from micromolar to nanomolar level. The new
      derivatives showed good selectivity against the trypsin-like and post-glutamyl
      peptide hydrolytic activities of this enzyme.

PMID- 11992771
TI  - Discovery of phenyl alanine derived ketoamides carrying benzoyl residues as novel
      calpain inhibitors.
AB  - Novel calpain inhibitors derived from phenyl alanine aldehydes or ketoamides
      carrying a benzoyl residue were prepared and evaluated for their biological
      potency. A brief structure-activity relationship elucidated the importance of
      ortho-substitutents in the benzoyl moiety. The most potent derivative, the
      ketoamide 19c, exhibited a K(i) of 6nM and represents a novel class of
      reversible, highly potent and non-peptidic calpain inhibitors.

PMID- 11992772
TI  - A novel type of nonsteroidal estrone sulfatase inhibitors.
AB  - Madurahydroxylactone (MHL) is a secondary metabolite produced by the soil
      bacterium Nonomuria rubra and belongs to the family of
      benzo[a]naphthacenequinones. We report the initial results and structure-activity
      relationships of our study into a series of thiosemicarbazone derivatives of
      madurahydroxylactone as potential nonsteroidal inhibitors of the enzyme estrone
      sulfatase. The most active compound, the cyclohexylthiosemicarbazone, was shown
      to be a non-competitive inhibitor with a K(i) of 0.35microM. This compound is
      devoid of estrogenic properties and showed low acute toxicity in the hen's
      fertile egg screening test.

PMID- 11992773
TI  - Design, synthesis and biochemical evaluation of AC ring mimics as novel
      inhibitors of the enzyme estrone sulfatase (ES).
AB  - We report the initial results of our study into a series of simple 4'-O-sulfamoyl
      4-biphenyl based compounds as novel inhibitors of the enzyme estrone sulfatase
      (ES). The results of the study show that these compounds are potent inhibitors,
      possessing greater inhibitory activity than COUMATE, but weaker inhibitory
      activity than EMATE or the tricyclic derivative of COUMATE, namely 667-COUMATE.
      Furthermore, the compounds are observed to be irreversible inhibitors.

PMID- 11992774
TI  - Novel histone deacetylase inhibitors: N-hydroxycarboxamides possessing a terminal
      bicyclic aryl group.
AB  - Utilizing tranexamic acid as a starting material, a series of N
      hydroxycarboxamides were synthesized in order to seek new histone deacetylase
      (HDAC) inhibitors. Further structure optimization involving the replacement of
      the 1,4-cyclohexylene group with the 1,4-phenylene group yielded the promising
      HDAC inhibitors which possess a terminal bicyclic aryl amide.

PMID- 11992775
TI  - Synthesis and evaluation of new antimalarial analogues of quinoline alkaloids
      derived from Cinchona ledgeriana Moens ex Trimen.
AB  - In the course of attempts to develop antimalarial drugs, we have designed and
      synthesized a series of quinoline alkaloide derivatives. Three of them, N-(4
      methoxy-3,5-di-tert-butylbenzyl)cinchonidinium bromide (OSL-5), O-benzyl-N-(3,5
      di-tert-butyl-4-methoxybenzyl)cinchonidinium bromide (OSL-7), and N-(3,5-di-tert
      butyl-4-methoxybenzyl)quininium bromide (OSL-14) show potent activity against
      Plasmodium falciparum.

PMID- 11992776
TI  - Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor
      antagonists.
AB  - The synthesis of novel 3-(octahydropyrido[1,2-a]pyrazin-2-yl)- and 3
      (hexahydropyrrolo[1,2-a]pyrazin-2-yl)phenyl-2-benzo[b]thiophene sulphonamide
      derivatives 3, (S)-4 and (R)-4 is described. The compounds show high affinity for
      the 5-HT6 receptor, excellent selectivity against a range of other receptors and
      good brain penetration.

PMID- 11992777
TI  - Discovery and initial SAR of imidazoquinoxalines as inhibitors of the Src-family
      kinase p56(Lck).
AB  - We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck
      with excellent potency (IC50s<5 nM) as well as good cellular activity against T
      cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the
      requirement for the core heterocycle in addition to an optimal 2,6-disubstituted
      aniline group.

PMID- 11992779
TI  - Antifungal sordarins. part 3: synthesis and structure-activity relationships of
      2',3'-fused oxirane derivatives.
AB  - A number of new 2',3'-fused oxirane derivatives were synthesized for structure
      activity relationship study. Many of these derivatives exhibit high potency
      against Candida spp. In addition, sordarin manno epoxide derivative 6 presents in
      vivo therapeutic effect in mice and is considered a promising antifungal lead
      within this series.

PMID- 11992778
TI  - Structure-based design of peptidomimetic antagonists of p56(lck) SH2 domain.
AB  - Starting from the tetrapeptide Ac-pYEEI-NHMe and using a structure-based
      approach, we have designed and synthesised a peptidomimetic ligand for p56(lck)
      SH2 domain containing a conformationally restricted replacement for the two
      glutamate residues. We have explored replacments for the isoleucine residue in
      the pY+3 pocket and thus identified 1-(R)-amino-3-(S)-indaneacetic acid as the
      most potent replacement. We also report the X-ray crystal structures of two of
      the antagonists.

PMID- 11992780
TI  - Shikonin derivatives: synthesis and inhibition of human telomerase.
AB  - We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and
      acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory
      activity against the telomerase enzyme, except cyclo-derivatives.

PMID- 11992781
TI  - Synthesis of highly potent and selective hetaryl ureas as integrin alpha(V)beta3
      receptor antagonists.
AB  - Solid-phase synthesis and SAR of integrin alpha(V)beta3-receptor antagonists
      containing a urea moiety as non-basic guanidine mimetic are described. The most
      potent compounds exhibited IC(50) values towards alpha(V)beta3 in the nanomolar
      range and high selectivity versus related integrins like alpha(IIb)beta3. For
      selected examples efficacy in functional cellular assays is demonstrated.

PMID- 11992782
TI  - Syntheses and bioactivities of novel carbamates combining platelet activating
      factor (PAF) receptor antagonist with thromboxane synthase inhibitor (TxSI).
AB  - Synthesis of carbamates 3b which possess dual-acting PAF antagonist/TxSI using
      unstable esters 1, diazepines 2, K2CO3 and 18-crown-6 is described.

PMID- 11992783
TI  - Synthesis and biological activity of selective pipecolic acid-based TNF-alpha
      converting enzyme (TACE) inhibitors.
AB  - A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4
      hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The
      potency and selectivity of TACE inhibition is dramatically influenced by the
      nature of the sulfonamide group which interacts with the S1' site of the enzyme.
      Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with
      >100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl
      substituents on the ortho position of the benzyl ether moiety give the most
      potent inhibition of TNF-alpha release in LPS-treated human whole blood.

PMID- 11992784
TI  - A unique unnatural base pair between a C analogue, pseudoisocytosine, and an A
      analogue, 6-methoxypurine, in replication.
AB  - Pseudoisocytidine, a C-nucleoside analogue of cytosine, has two possible isomers
      of the H1- and H3-forms. Enzymatic incorporation experiments confirmed the
      existence of the two isomers in solution, and the 2'-deoxyribonucleoside
      triphosphate of pseudoisocytosine (PIC) was incorporated into DNA opposite both
      guanine and 6-methoxypurine (M) by the Klenow fragment of Escherichia coli DNA
      polymerase I. In addition to the PIC*M pairing in replication, M also functioned
      as an A analogue and T was efficiently incorporated opposite M. Thus, the PIC*M
      pair is regarded as a base pair between a C analogue and an A analogue, and can
      mediate the interconversion between the G*C and A*T base pairs. The combination
      of PIC and M could be used as a G*C<-->A*T transition mutagen.

PMID- 11992785
TI  - Heterocyclic nucleoside analogues: design and synthesis of antiviral, modified
      nucleosides containing isoxazole heterocycles.
AB  - We have designed and synthesized novel antiviral nucleoside analogues, which
      consist of isoxazole rings as modified sugars and nucleobases (thymine, uracil,
      and 5-fluorouracil) with a methylene linker between them. These compounds
      represent a new class of modified nucleoside analogues and some of them show
      potent antiviral activities against Polio virus (Coxsackie B type 3 and Vesicular
      Stomatitis).

PMID- 11992786
TI  - Identification of potent and selective oxytocin antagonists. Part 1: indole and
      benzofuran derivatives.
AB  - Studies to discover novel, potent and selective oxytocin antagonists are
      reported. Combinatorial libraries designed to find novel replacements of
      fragments of oxytocin antagonist L-371,257, identified pyrimidine, thiazole,
      indole and benzofuran as potential alternatives to the benzoic acid moiety of L
      371,257. Additional investigations identified indole and benzofuran derivatives
      with potent oxytocin antagonist activity.

PMID- 11992787
TI  - Identification of potent and selective oxytocin antagonists. Part 2: further
      investigation of benzofuran derivatives.
AB  - The paper covers continuing efforts to discover novel, potent and selective
      oxytocin antagonists. Further benzofuran derivatives with potent oxytocin
      antagonist activity and good pharmacokinetic parameters are reported. Efforts to
      improve the in vivo activity of the series are described.

PMID- 11992788
TI  - Synthesis and biological evaluation of an N10-Psec substituted pyrrolo[2,1
      c][1,4]benzodiazepine prodrug.
AB  - The first example of an N10-protected (e.g., Psec, 15) pyrrolo[2,1
      c][1,4]benzodiazepine (PBD) analogue that retains significant cytotoxicity in a
      number of tumour cell lines is reported. This prototype could lead to a new
      generation of clinically useful N10-protected PBD prodrugs.

PMID- 11992789
TI  - Aromatic farnesyl diphosphate analogues: vinyl triflate-mediated synthesis and
      preliminary enzymatic evaluation.
AB  - A stereocontrolled vinyl triflate-based synthetic route has been used to prepare
      four analogues of farnesyl diphosphate (FPP) where the terminal isoprene units
      have been replaced with aromatic moieties. Two of these analogues exhibit no
      productive interaction with protein farnesyltransferase, but the 2-naphthyl
      derivative 2 is a modest inhibitor of the enzyme, and the para-biphenyl
      derivative 4 is a surprisingly effective alternative substrate.

PMID- 11992790
TI  - Use of parallel-synthesis combinatorial libraries for rapid identification of
      potent FKBP12 inhibitors.
AB  - Using simple, inexpensive equipment, we have used solution-phase parallel
      synthesis to rapidly prepare hundreds of sulfonamide- and urea-containing FKBP
      inhibitors, resulting in rapid identification of extremely potent compounds in
      these series.

PMID- 11992791
TI  - Solid-phase synthesis of FKBP12 inhibitors: N-sulfonyl and N
      carbamoylprolyl/pipecolyl amides.
AB  - In parallel with our work on solution-phase parallel synthesis of ligands for the
      rotamase enzyme FKBP12, we herein report a methodology for the solid-phase
      synthesis of two classes of inhibitor, N-sulfonyl and N-carbamoylprolyl and
      pipecolyl amides along with their in vitro/in vivo biological results.

PMID- 11992794
TI  - Multidetector CT and three-dimensional imaging of the pancreas: state of the art.

PMID- 11992795
TI  - Endoscopic ultrasonography.

PMID- 11992796
TI  - Magnetic resonance imaging of the pancreas in 2001.

PMID- 11992797
TI  - Imaging of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron
      emission tomography.

PMID- 11992798
TI  - The value of laparoscopy in the management of ampullary, duodenal, and distal
      bile duct tumors.
AB  - Laparoscopy identifies radiologically occult advanced disease in patients with
      pancreatic adenocarcinoma. The value of laparoscopy in the management of peri
      ampullary tumors was determined. One hundred forty-four patients with
      radiologically resectable nonpancreatic adenocarcinoma, periampullary tumors were
      identified from a prospective database between August 1993 and December 2000.
      Criteria for laparoscopic unresectability included histologically proved
      peritoneal or hepatic metastases, distant nodal involvement, arterial
      involvement, and local extension outside the resection field. Median age at
      operation was 70 years (range 31 to 87 years) and 56% of the patients were men.
      An adequate laparoscopy was performed in 134 cases (93%). Laparoscopy identified
      13 patients (10%) with unresectable disease. Of 121 patients with laparoscopic
      resectable disease, 111 (92%) went on to subsequent resection; CT correctly
      predicted resectability in 82%. Laparoscopy spared 36% of unresectable patients a
      nontherapeutic laparotomy. Patients with resectable disease were treated by
      pancreaticoduodenectomy (n = 91, 76%), ampullectomy (n = 12, 10%), duodenal
      resection (n = 10, 9%), or bile duct excision (n = 6, 5%). The addition of
      diagnostic laparoscopy to dynamic CT scanning in this selected patient population
      identifies an additional 10% of patients with unresectable disease. We believe
      that laparoscopy should be used in a selective manner for preoperative staging of
      patients suspected of having nonpancreatic periampullary tumors.

PMID- 11992799
TI  - En bloc resection for locally advanced cancer of the pancreas: is it worthwhile?
AB  - The benefit of radical surgical resection of contiguously involved structures for
      locally advanced pancreatic cancer is unclear. The aim of this study was to
      examine patient outcome after extended pancreatic resection for locally advanced
      tumors and to determine if any subset of extended resection affected outcome. We
      retrospectively reviewed the records of 116 patients with adenocarcinoma of the
      pancreas, who underwent extirpative pancreatic surgery between 1987 and 2000. Of
      the 116 patients, 37 (32%) required resection of surrounding structures (group
      I), and 79 patients (68%) underwent standard pancreatic resections (group II). In
      all cases, all macroscopic disease was excised. In group I a total of 46
      contiguously involved structures were resected: vascular in 25 patients (54%),
      mesocolon in 16 (35%) (colic vessels in 3, colon in 13), adrenal in three (7%),
      liver in one (2%), stomach in one (2%) (for a tumor in the tail of the pancreas),
      and multiple structures in four. Excision of regional blood vessels included the
      superior mesenteric vein and/or portal vein in 16, hepatic artery in five, and
      celiac axis in four. No differences between groups I and II were detected for any
      of the following parameters: age, sex, history of previous operation, estimated
      blood loss, or hospital stay. For the entire cohort the morbidity and mortality
      were 38% and 1.7%, respectively, and these rates were similar in the two groups.
      Adjuvant therapy was administered to more than 90% of patients in both groups.
      However, patients in group I were more likely to have received neoadjuvant
      therapy (76% vs. 42%, P = 0.001). Total pancreatectomy and distal pancreatectomy
      were more often performed in group I (P = 0.005). Additionally, the median
      operative time was longer (8.5 hours compared to 6.9 hours (P = 0.0004)). Both
      groups had similar rates of microscopically positive margins and involved lymph
      nodes, as well as total number of lymph nodes removed. The median survival was 26
      months for patients in group I and 16 months for patients in group II (P = 0.08).
      The median disease-free survival for groups I and II was 16 months and 14 months,
      respectively (P = 0.88). In comparing patients in group I, who underwent vascular
      resection vs. mesocolon (colon or middle colic vessels) resection, the median
      survival was 26 months and 19 months, respectively (P = 0.12). We were unable to
      detect a difference in outcome for patients with locally advanced cancers
      requiring extended pancreatic resections compared to patients with standard
      resections. En bloc resection of involved surrounding structures, to completely
      extirpate all macroscopic disease, may be of benefit in selected patients with
      locally advanced disease, particularly when combined with preoperative
      chemoradiation therapy.

PMID- 11992800
TI  - Specific targeting of tumor vasculature by diphtheria toxin-vascular endothelial
      growth factor fusion protein reduces angiogenesis and growth of pancreatic
      cancer.
AB  - Tumor vessels abundantly express receptors for vascular endothelial growth factor
      (VEGF), a mediator of neoangiogenesis. The aim of this study was to specifically
      target and damage the vasculature of pancreatic cancer (PaCa) by fusing VEGF to
      diphtheria toxin (DT), which inhibits protein synthesis of target cells. DT-VEGF
      fusion protein was produced in vector pGEX-KG and expressed in E. coli SG12036.
      Human PaCa cell lines (HPAF-2 and AsPC-1) and human endothelial cells (HUVEC)
      were exposed to DT-VEGF (10 ng/ml - 10,000 ng/ml). Proliferation was assessed
      after 3 days. One mm(3) fragments of subcutaneous PaCa donor tumors were
      implanted into the pancreas of nude mice that received either DT-VEGF (200
      microg/kg, every other day) or phosphate-buffered saline intraperitoneally for 14
      weeks. Tumor volume, metastatic spread, and animal weight were determined at
      autopsy. Microvessel density was analyzed in CD31-stained tumor sections.
      Proliferation of PaCa cells was inhibited at high concentrations of DT-VEGF
      (>1000 ng/ml). DT-VEGF decreased the growth of HUVEC at 10 ng/ml. In vivo, DT
      VEGF reduced tumor volume (HPAF-2, 76%; AsPC-1, 53%), microvessel density (HPAF
      2, 54%; AsPC-1, 62%), and tumor spread (HPAF-2, 89%; AsPC-1, 50%). Survival was
      increased (HPAF-2, 7/8 vs. 4/8 animals; AsPC-1, 6/8 vs. 1/8 animals). Weight was
      not influenced by DT-VEGF. The DT-VEGF effect is due to its toxic action on the
      tumor vasculature rather than to direct inhibition of PaCa cell growth. DT-VEGF
      therapy was not associated with systemic side effects.

PMID- 11992801
TI  - Human heparanase-1 gene expression in pancreatic adenocarcinoma.
AB  - Extracellular matrix degradation is an essential step that allows tumor cells to
      penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR1) is an
      endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief
      component of the extracellular matrix. HPR1 is not expressed in normal epithelial
      cells but can be detected in a variety of malignancies. In the present study, we
      examined HPR1 expression in pancreatic cancer by using in situ hybridization and
      tested whether HPR1 expression correlated with any clinicopathlogic parameters.
      HPR1 was not detected in the ductal cells of normal pancreas samples obtained
      from 10 patients at autopsy. However, HPR1 was detected in 77 (78%) of 99
      pancreatic adenocarcinomas. Among them, 69 (78%) of 89 primary pancreatic
      adenocarcinomas and 8 (80%) of the 10 metastases were HPR1 positive. Age, sex,
      tumor stage, and lymph node status were not predictive of HPR1 expression. Log
      rank test of the Kaplan-Meier survival curves revealed that HPR1 expression in
      early-stage tumors was associated with decreased survival. HPR1 expression was
      frequent in pancreatic adenocarcinomas and was associated with decreased survival
      in early-stage tumors. This suggests that HPR1 may contribute to the highly
      invasive and early metastatic behavior of pancreatic cancer.

PMID- 11992803
TI  - Laparoscopic management of giant type III hiatal hernia and short esophagus.
      Objective follow-up at three years.
AB  - We wished to evaluate the long-term effectiveness of the laparoscopic Hill repair
      in the treatment of type III hiatal hernia. Fifty-two patients underwent
      laparoscopic repair of a type III hiatal hernia. No esophageal lengthening
      procedures were performed. Short esophagus was determined from the operative
      record. Late symptomatic follow-up and a satisfaction questionnaire were
      completed in 71% (37/52) of patients at a mean of 39 months (range 6 to 84
      months). Esophagrams were completed in 65% (34/52) of patients at a mean of 37
      months (range to 84 months) after repair. Eighty-one percent were without any
      adverse symptoms, and 86% rated outcome as excellent or good at 39 months.
      Symptoms requiring treatment were present in 19% (7/37). Esophagrams revealed a
      recurrent hernia in 32% (11/34) of patients of whom 36% (4/11) were asymptomatic.
      Six patients with short esophagus underwent esophagram with one recurrence
      identified (17%). This was compared with 28 patients without short esophagus, of
      whom 10 had a recurrence (35%) (P = 0.70). The laparoscopic Hill repair provides
      long-term satisfaction and relief of symptoms. The incidence of anatomic
      recurrence on video esophagram is high and does not always correlate with
      symptoms. The presence of short esophagus does not play a role in recurrence when
      the Hill repair is used.

PMID- 11992802
TI  - Quality of life in chronic pancreatitis: a prospective trial comparing classical
      whipple procedure and duodenum-preserving pancreatic head resection.
AB  - Few data are available with respect to quality of life after pancreatic head
      resection in patients with chronic pancreatitis. The aim of this study was to
      compare the classical Whipple pancreatoduodenectomy (PD) with the Beger duodenum
      preserving pancreatic head resection (DPPHR), in terms of quality of life, using
      standardized, valid, and reliable questionnaires. Sixty-five consecutive patients
      were included in this study. The PD procedure was chosen when pancreatic cancer
      could not be ruled out (n = 30); otherwise DPPHR was performed (n = 35). Quality
      of life was measured prospectively three times with the European Organization for
      Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ-C30)
      and the Gastrointestinal Quality-of-Life Index (GIQLI). Both procedures led to a
      significant improvement in quality of life, especially with regard to pain
      status. However, at the second follow-up examination (18 to 24 months
      postoperatively), all functional scales and the most important symptom scales of
      the EORTC QLQ-C30 revealed a better quality of life in the DPPHR group compared
      to the PD group. After classical PD, more patients seem to develop diabetes
      mellitus. The EORTC QLQ-C30 was found to be a better tool for quality-of-life
      assessment than the GIQLI in patients with chronic pancreatitis.

PMID- 11992804
TI  - Laryngoscopy and pharyngeal pH are complementary in the diagnosis of
      gastroesophageal-laryngeal reflux.
AB  - Pharyngeal pH monitoring and laryngoscopy are routinely used to diagnose
      gastroesophageal-laryngeal reflux as a cause of respiratory symptoms. Although
      their use seems intuitive, their ultimate diagnostic value is yet to be defined.
      We studied 10 asymptomatic (control) subjects and 76 patients with respiratory
      symptoms. Both patients and control subjects were given a symptom questionnaire.
      Each underwent direct laryngoscopy using the reflux finding score (RFS) to grade
      laryngeal injury, esophageal manometry, and 24-hour esophagopharyngeal pH
      monitoring. The patients were then classified as RFS+, if the score was greater
      than 7, and pharyngeal reflux (PR)+, if they had more than one episode of PR
      detected during pH monitoring. The most common symptoms reported by patients were
      hoarseness (87%), cough (53%), and heartburn (50%). Control subjects had a
      significantly lower RFS (2.1 vs. 9.6, P < 0.01) and fewer episodes of PR (0.2 vs.
      3.4, P < 0.01), than patients. None of the control subjects had more than one
      episode of PR during a 24-hour period. Fifty patients (66%) were RFS+ and 26
      (34%) were RFS-. Thirty-two patients (42%) were PR+ and 44 (58%) were PR-.
      Fifteen patients had a normal RFS and no PR (group I = RFS-/PR-). Forty patients
      had discordance between the laryngoscopic findings and the pH monitoring (group
      II = RFS-/PR+ or RFS+/PR-). Twenty-one patients had both an abnormal RFS and PR
      (group III = RFS+/PR+). Patients in group III had significantly higher heartburn
      scores and distal esophageal acid exposure. Eighty-three percent of patients in
      group III but only 44% in group I improved their respiratory symptoms as a result
      of antireflux therapy. An abnormal PR or RFS differentiates patients with
      laryngeal symptoms from control subjects. Agreement between PR and RFS helps
      establish or refute the diagnosis of gastroesophageal reflux as a cause of
      laryngeal symptoms. Patients who are RFS+ and PR- may have laryngeal injury from
      another source, whereas patients who are RFS- and PR+ may not have acid entering
      the larynx, despite the presence of PR. Patients who are RFS+ and PR+ have more
      severe gastroesophageal reflux disease and their reflux causes laryngeal damage.
      Laryngoscopy and pharyngeal pH monitoring should be considered complementary
      studies in establishing the diagnosis of laryngeal injury induced by
      gastroesophageal reflux. ( J GASTROINTEST SURG 2002;6:189-194.)

PMID- 11992805
TI  - Malabsorptive gastric bypass in patients with superobesity.
AB  - Weight loss in superobese patients has been problematic after conventional
      gastric restrictive operations including conventional Roux-en-Y gastric bypass
      (RYGB). The goal of the present study was to compare weight loss in patients with
      superobesity (body mass index > or =50 kg/m(2)) using a distal RYGB (D-RY) in
      which the Roux-en-Y anastomosis was performed 75 cm proximal to the ileocecal
      junction (N = 47) vs. patients who had Roux limbs of 150 cm (N = 152) and 50 to
      75 cm (N = 99). All operations incorporated the same gastric restrictive
      parameters. Minimum follow-up was 3 years and ranged to 16 years. Weight loss and
      reduction in body mass index were significantly greater after D-RY vs. both RYGB
      150 cm and short RYGB and in RYGB-150 cm vs. short RYGB through 5 years. Mean
      percentage of excess weight loss peaked at 64% after DRY, at 61% after RYGB-150
      cm, and at 56% after short RYGB. Weight loss maintenance through 5 years was
      correlated with Roux limb length with D-RY greater than RYGB-150 cm greater than
      short RYGB. More than 95% of obesity-related comorbid conditions improved or
      resolved with weight loss. There was no difference in the early postoperative
      morbidity rates: 9% after D-RY; 8% after RYGB-150 cm; and 2% after short RYGB
      with one death (0.3%). All D-RY patients had at least one postoperative metabolic
      abnormality. Anemia was significantly more common after D-RY vs. the shorter RYGB
      with no difference in the incidence of metabolic sequelae between RYGB-150 cm and
      short RYGB. No operations were reversed or modified for nutritional
      complications. Two D-RY patients required total parenteral nutrition for protein
      malnutrition. These results show that Roux limb length is correlated with weight
      loss in superobese patients. However, the greater incidence of metabolic sequelae
      after D-RY vs. RYGB-150 cm calls into question its routine use in superobese
      patients undergoing bariatric surgery. We conclude that some degree of
      malabsorption should be incorporated into bariatric operations performed in
      superobese patients to achieve satisfactory long-term weight loss.

PMID- 11992806
TI  - Roux-en-Y gastric bypass after previous unsuccessful gastric restrictive surgery.
AB  - In the treatment of morbid obesity, simple gastric restrictive methods such as
      silicone adjustable gastric banding, vertical banded gastroplasty, and
      nonadjustable gastric banding often fail to control weight in the long run or
      give rise to intolerable side effects. Here we review our results from conversion
      of such failures to Roux-en-Y gastric bypass. The study comprised 44 patients
      (median age 42 years, range 24 to 60 years) who underwent revision surgery in
      1996 and 1997. Body mass index at revision was 35 kg/m(2) (range 21 to 49
      kg/m(2)). Previous bariatric procedures included silicone adjustable gastric
      banding (n = 26), vertical banded gastroplasty (n = 13), and gastric banding (n =
      5). The most common reasons for conversion after silicone adjustable gastric
      banding and nonadjustable gastric banding were band erosion (n = 12) and
      esophagitis (n = 11). Staple line disruption (n = 12) with subsequent weight loss
      failure was the primary cause after vertical banded gastroplasty. There were no
      postoperative deaths or anastomotic leaks. One patient underwent reexploration
      because of an infected hematoma. Reflux symptoms and vomiting resolved promptly.
      At global assessment 2 years later, 70% of the patients were very satisfied.
      Median body mass index had decreased to 28 kg/m(2) (range 18 to 42 kg/m(2)). No
      patient was lost to follow-up. As reported previously, failure after vertical
      gastric banding can be treated by conversion to Roux-en-Y gastric bypass with
      good results. In this study we found that failure after silicone adjustable
      gastric banding can be treated successfully with Roux-en-Y gastric bypass as
      well.

PMID- 11992808
TI  - Predictors of microvascular invasion in patients with hepatocellular carcinoma
      who are candidates for orthotopic liver transplantation.
AB  - Microvascular invasion affects survival after orthotopic liver transplantation
      (OLT) for hepatocellular carcinoma (HCC). We sought to identify preoperative
      predictors of microvascular invasion in patients with HCC who were candidates for
      OLT. A cohort of 245 patients who underwent resection for HCC and fulfilled the
      criteria for OLT (i.e., single tumors < or =5 cm or no more than three tumors <
      or =3 cm) were identified from a multi-institutional database. Thirty-three
      percent of the patients had pathologic evidence of microvascular invasion. Thirty
      percent of patients with single tumors and 47% with multiple tumors had
      microvascular invasion (P = 0.04). Only 25% of patients with tumors smaller than
      < or =2 cm had microvascular invasion, compared to 31% and 50% with tumors
      greater than 2 to 4 cm or larger than 4 cm, respectively (P = 0.01). Tumor grade
      was highly correlated with microvascular invasion: 12% of patients with well
      differentiated tumors had microvascular invasion, compared to 29% and 50% with
      moderately or poorly differentiated tumors, respectively (P < 0.001). The
      independent predictors of microvascular invasion were tumor size greater than 4
      cm (odds ratio [OR], 3.0, 95% confidence interval [CI ], 1.2 to 7.1), and high
      tumor grade (OR, 6.3; 95% CI, 2.0 to 19.9). Tumor size and grade are strong
      predictors of microvascular invasion. A tumor biopsy with pathologic grading at
      the time of pretransplantation ablative therapy could improve selection of
      patients with HCC for OLT.

PMID- 11992807
TI  - Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced
      gastric cancer.
AB  - We examined the role of neoadjuvant therapy in downstaging locally advanced
      gastric cancer. Preoperative staging was performed with a combination of CT
      scans, endoscopic ultrasonography and/or laparoscopy, and laparoscopic
      ultrasonography. Patients with T > or =3 tumors and/or node-positive disease by
      preoperative clinical staging were eligible for entry. Neoadjuvant therapy
      consisted of two cycles of CPT-11 (75 mg/m(2)) with cisplatin (25 mg/m(2)) weekly
      four times every 6 weeks. This was followed by resection with D2 lymph node
      dissection and two cycles of intraperitoneal chemotherapy with floxuridine and
      cisplatin. Twenty-two patients were entered into the study (4 with T3N0 disease
      and 18 with T3N1 disease). Induction chemotherapy was well tolerated with major
      toxicities being neutropenia and diarrhea. A median of 78%/75% of the planned
      dosage of CPT-11/cisplatin was delivered. Two patients withdrew consent during
      the first cycle and were lost to follow-up. One patient progressed to stage IV
      disease during induction chemotherapy and did not undergo surgery. Nineteen
      patients underwent surgery. One patient had undetected stage IV disease (liver)
      and underwent a palliative R2 resection. Of the 18 remaining patients, 17 had
      curative R0 resections and one had a palliative R1 resection. A median of 21
      lymph nodes (range 1 to 121) were examined histologically. There was one
      postoperative death. Surgical morbidity did not appear to increase after the
      neoadjuvant regimen. The median postoperative length of hospital stay was 9 days
      (range 3 to 75 days). Postoperative pathologic staging yielded 16% T3 lesions
      compared to 85% before treatment based on clinical staging; postoperative
      American Joint Committee on Cancer staging yielded 37% stage IIIA disease
      compared to 70% stage IIIA before treatment. With a median follow-up of 15
      months, median survival has not yet been reached. We conclude that CPT-11-based
      neoadjuvant therapy downstages locally advanced gastric cancer. Further follow-up
      is necessary to determine the ultimate impact of this combination therapy on
      recurrence and survival.

PMID- 11992809
TI  - Ninety-five cases of intestinal transplantation at the University of Miami.
AB  - Intestinal failure requiring total parenteral nutrition (TPN) is associated with
      significant morbidity and mortality. Intestinal transplantation can be a
      lifesaving option for patients with intestinal failure who develop serious TPN
      related complications. The aim of this study was to evaluate survival, surgical
      technique, and patient care in patients treated with intestinal transplantation.
      We reviewed data collected from 95 consecutive intestinal transplants performed
      between December 1994 and November 2000 at the University of Miami. Fifty-four of
      the patients undergoing intestinal transplantation were children and 41 were
      adults. The series includes 49 male and 46 female patients. The causes of
      intestinal failure included mesenteric venous thrombosis (n = 12), necrotizing
      enterocolitis (n = 11), gastroschisis (n = 11), midgut volvulus (n = 9), desmoid
      tumor (n = 8), intestinal atresia (n = 6), trauma (n = 5), Hirschsprung's disease
      (n = 5), Crohn's disease (n = 5), intestinal pseudoobstruction (n = 4), and
      others (n = 19). The procedures performed included 27 isolated intestine
      transplants, 28 combined liver and intestine transplants, and 40 multivisceral
      transplants. Since 1998, we have been using daclizumab (Zenepax) for induction of
      immunosuppression and zoom videoendoscopy for graft surveillance. We began to use
      intense cytomegalovirus prophylaxis and systemic drainage of the portal vein. The
      1-year patient survival rates for isolated intestinal, liver and intestinal, and
      multivisceral transplantations were 75%, 40%, and 48%, respectively. Since 1998,
      the 1-year patient and graft survival rates for isolated intestinal transplants
      have been 84% and 72%, respectively. The causes of death were as follows: sepsis
      after rejection (n = 14), respiratory failure (n = 8), sepsis (n = 6), multiple
      organ failure (n = 4), arterial graft infection (n = 3), aspergillosis (n = 2),
      post-transplantation lymphoproliferative disease (n = 2), intracranial hemorrhage
      (n = 2), and fungemia, chronic rejection, graft vs. host disease, necrotizing
      enterocolitis, pancreatitis, pulmonary embolism, and viral encephalitis (n = 1
      case of each). Intestinal transplantation can be a lifesaving alternative for
      patients with intestinal failure. The prognosis after intestinal transplantation
      is better when it is performed before the onset of liver failure. Rejection
      monitoring with zoom videoendoscopy and new immunosuppressive therapy with
      sirolimus, daclizumab, and campath-1H have contributed to the improvement in
      patient survival.

PMID- 11992810
TI  - Role of extrinsic innervation in jejunal absorptive adaptation to subtotal small
      bowel resection: a model of segmental small bowel transplantation.
AB  - Segmental small bowel transplantation offers theoretic advantages over total
      jejunoileal transplantation, but the regional ability of the transplanted segment
      to adapt is unknown. Absorption was measured in an 80 cm jejunal segment via a
      triple-lumen perfusion technique. Separate experiments measuring absorption of
      four nutrients (glucose, glutamine, oleic acid, and taurocholic acid) were
      performed before and 2 and 12 weeks after operative intervention. Control dogs
      (CON, n = 6) underwent distal 50% enterectomy. Experimental dogs (EXT DEN, n =
      6), in addition to resection, underwent complete extrinsic denervation of the
      remaining jejunum. All dogs developed diarrhea, which resolved in all CON dogs
      but persisted in all EXT DEN dogs. Maximal weight loss was greater in the EXT DEN
      group. Glucose and oleate absorption was decreased 2 weeks after ileal resection
      in both the CON and EXT DEN dogs; glutamine absorption was decreased at 2 weeks
      in EXT DEN dogs only. Taurocholate and water absorption remained unchanged in
      both groups. Absorption of all solutes returned to baseline at 12 weeks in both
      groups. Despite greater weight loss and persistent diarrhea in EXT DEN dogs, at
      12 weeks there were no differences in net absorptive fluxes between the EXT DEN
      and the CON group after extrinsic denervation. The extrinsic denervation
      necessitated by small bowel transplantation does not appear to blunt the net
      jejunal adaptive response to total ileal resection, but may temporarily alter
      glutamine absorption.

PMID- 11992811
TI  - Donor hepatic function: a factor in postreperfusion syndrome.
AB  - Reperfusion of support livers after cold preservation produces hemodynamic
      instability (i.e., postreperfusion syndrome) in the recipient during both
      orthotopic liver transplantation and extracorporeal liver perfusion. We evaluated
      the effect of the normal porcine cold-preserved support liver on healthy
      recipient hemodynamics and in situ liver function during extracorporeal liver
      perfusion. Support livers were harvested from Yorkshire pigs and reperfused in an
      extracorporeal circuit with a healthy, anesthetized recipient pig. Correlation
      analyses were performed between support liver variables of function (oxygen
      consumption, bile flow, and biliary phospholipid and cholesterol output) and both
      recipient hemodynamic stability (heart rate, blood pressure, urine output, and
      vasopressor use) and hepatic function (bile flow and biliary phospholipid
      secretion). The data indicate that optimally functioning support livers are
      associated with improved recipient hemodynamic stability manifested by decreased
      recipient heart rate and vasopressor use and increased recipient urine output.
      Support livers exhibiting poor biliary secretory function (i.e., bile flow and
      phospholipid output) were associated with similarly diminished recipient liver
      biliary secretory function. These data indicate that the functional condition of
      the support liver after harvest and cold preservation may influence both
      recipient hemodynamic parameters and the endogenous function of the recipient
      liver.

PMID- 11992812
TI  - Local, intrahepatic, and systemic recurrence patterns after radiofrequency
      ablation of hepatic malignancies.
AB  - The objective of this study was to describe the recurrence patterns in patients
      with unresectable hepatic malignancies treated with radiofrequency ablation
      (RFA). As RFA is applied more widely to patients with hepatic tumors, a better
      understanding of the biologic behavior of these tumors and the risk of
      recurrence, both in the liver and systemically, is needed. A multidisciplinary
      team evaluated patients referred for RFA and followed them prospectively to
      assess local, intrahepatic, and extrahepatic disease recurrence and complication
      rates. Forty-five patients with 143 lesions and a minimum follow-up of 6 months
      (median 19.5 months) were treated. Overall, 7.7% of treated lesions had local
      recurrence. New intrahepatic disease was seen in 49% of patients, and 24% had
      evidence of new systemic tumor progression. Patients with colorectal metastatic
      lesions > or =4 cm at the time of the first RFA were more likely to present with
      local recurrence (P = 0.048). Complications occurred in 27% of patients. Although
      RFA has a satisfactory local failure rate and safety profile, the patient
      population being treated is at high risk of developing new disease. Multimodality
      adjuvant therapy will be necessary to realize the full potential of hepatic
      malignancy control with RFA.

PMID- 11992813
TI  - Hepatic cryoablation-induced multisystem injury: bioluminescent detection of NF
      kappaB activation in a transgenic mouse model.
AB  - Hepatic injury from cryoablation has been associated with multisystem injury,
      including adult respiratory distress syndrome, renal insufficiency, and
      coagulopathy; but the responsible mechanisms have not been well defined. In the
      present study we investigated the role of the transcription factor NF-kappaB in
      the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in
      vivo system for determining NF-kappaB activity. Using transgenic mice expressing
      photinus luciferase under the control of the 5' HIV-LTR (an NF-kappaB-dependent
      promoter), we measured luciferase activity in the liver, lungs, and kidneys as a
      marker for NF-kappaB activity. Luciferase production was determined by in vivo
      bioluminescence and by luciferase assays of tissue homogenates. After measurement
      of basal luciferase activity, mice were treated with 35% hepatic cryoablation or
      sham laparotomy and injected with luciferin (0.75 mg/mouse). Photon emission from
      the liver, lungs, and kidneys was measured at multiple time points. Hepatic
      cryoablation induced a significant increase in photon emission by the liver,
      lungs, and kidneys, which correlated with markedly increased luciferase activity
      measured from each organ after death. Lung lavage 4 hours after cryoablation
      showed neutrophilic lung inflammation with increased MIP-2 levels compared with
      sham surgery. These findings demonstrate that 35% hepatic cryoablation is
      associated with NF-kappaB activation in the remnant liver and multiple distant
      sites, and may be causally related to the multisystem injury that is seen after
      direct liver injury.

PMID- 11992815
TI  - Number and size of stones in patients with asymptomatic and symptomatic
      gallstones and gallbladder carcinoma.

PMID- 11992818
TI  - Plant phosphate transporter genes help harness the nutritional benefits of
      arbuscular mycorrhizal symbiosis.

PMID- 11992819
TI  - Yet another plant thioredoxin.
AB  - Thioredoxins are widely distributed proteins that function in a broad spectrum of
      cellular reactions. Plant cells have well characterized chloroplast and cytosolic
      thioredoxin systems, but, unlike animals and yeast, a mitochondrial counterpart
      has not been clearly defined. Recently, a complete thioredoxin system has been
      described in plant mitochondria, opening a new door for the study of thioredoxins
      as well as mitochondria.

PMID- 11992820
TI  - GATEWAY vectors for Agrobacterium-mediated plant transformation.
AB  - Agrobacterium tumefaciens is the preferred method for transformation of a wide
      range of plant species. Commonly, the genes to be transferred are cloned between
      the left and right T-DNA borders of so-called binary T-DNA vectors that can
      replicate both in E. coli and Agrobacterium. Because these vectors are generally
      large, cloning can be time-consuming and laborious. Recently, the GATEWAY
      conversion technology has provided a fast and reliable alternative to the cloning
      of sequences into large acceptor plasmids.

PMID- 11992824
TI  - Hybrid seed production and the challenge of propagating male-sterile plants.
AB  - The introduction of hybrid crop varieties has enabled spectacular increases in
      productivity owing to hybrid vigor and increased uniformity. To produce hybrid
      seeds, a pollination control system is required to prevent unwanted self
      pollination. In crop species with hermaphrodite flowers, this can be a major
      challenge. Over the past decade, new pollination control systems have been
      developed with the aid of genetic engineering, mainly based on the generation of
      nuclear-encoded male sterility. The successful application of these systems for
      large-scale hybrid seed production depends on whether the male-sterile female
      parent line can be multiplied efficiently and economically. In spite of its
      relevance, the propagation of the male-sterile line has often been overlooked in
      the development of pollination control systems.

PMID- 11992825
TI  - Phototropins 1 and 2: versatile plant blue-light receptors.
AB  - Blue and ultraviolet-A light regulate a wide range of responses in plants,
      including phototropism, chloroplast migration and stomatal opening. However, the
      photoreceptors for these light responses have been identified only recently. The
      phototropins (phot1 and phot2) represent a new class of receptor kinases that
      appear to be exclusive to plants. Recent genetic analysis has shown that phot1
      and phot2 exhibit partially overlapping functions in mediating phototropism,
      chloroplast migration, and stomatal opening in Arabidopsis. Although significant
      progress has been made in understanding the early photochemical and biochemical
      events that follow phototropin excitation, the details of how this excitation
      activates such different responses remain to be elucidated.

PMID- 11992826
TI  - Priming in plant-pathogen interactions.
AB  - Plants can acquire enhanced resistance to pathogens after treatment with
      necrotizing attackers, nonpathogenic root-colonizing pseudomonads, salicylic
      acid, beta-aminobutyric acid and many other natural or synthetic compounds. The
      induced resistance is often associated with an enhanced capacity to mobilize
      infection-induced cellular defence responses - a process called 'priming'.
      Although the phenomenon has been known for years, most progress in our
      understanding of priming has been made only recently. These studies show that
      priming often depends on the induced disease resistance key regulator NPR1 (also
      known as NIM1 or SAI1) and that priming has a major effect on the regulation of
      cellular plant defence responses.

PMID- 11992827
TI  - Fatty acid-derived signals in plants.
AB  - Plants synthesize many fatty acid derivatives, several of which play important
      regulatory roles. Jasmonates are the best characterized examples. Jasmonate
      insensitive mutants and mutants with a constitutive jasmonate response have given
      us new insights into jasmonate signalling. The jasmonate biosynthesis mutant opr3
      allowed the dissection of cyclopentanone and cyclopentenone signalling, thus
      defining specific roles for these molecules. Jasmonate signalling is a complex
      network of individual signals and recent findings on specific activities of
      methyl jasmonate and (Z)-jasmone add to this picture. In addition, there are
      keto, hydroxy and hydroperoxy fatty acids that might be involved in cell death
      and the expression of stress-related genes. Finally, there are bruchins and
      volicitin, signal molecules from insects that are perceived by plants in the
      picomole to femtomole range. They highlight the importance of fatty acid-derived
      molecules in interspecies communication and in plant defence.

PMID- 11992828
TI  - Towards genomic and proteomic studies of protein phosphorylation in plant
      pathogen interactions.
AB  - Phosphorylation is an effective method of post-translational protein modification
      but understanding its significance is hindered by its biological complexity. Many
      protein kinases and phosphatases have been identified that connect signal
      perception mechanisms to plant defence responses. Recent studies of mitogen
      activated protein kinases, calcium-dependent protein kinases and other kinases
      and phosphatases have revealed some important mechanisms, but have also raised
      new questions. The regulation of any phosphorylation pathway is complex and
      dynamic. There are many protein kinases and phosphatases in the plant genome,
      which makes it hard to delineate the phosphorylation machinery fully. Genomics
      and proteomics have already identified new components and will continue to
      influence the study of phosphorylation profoundly in plant-pathogen interactions.

PMID- 11992829
TI  - T-DNA of Agrobacterium tumefaciens: 25 years and counting.

PMID- 11992832
TI  - Changing concepts in the management of renal oncocytoma.

PMID- 11992833
TI  - Biotechnology and drug discovery--the future is here: a guide for the practicing
      urologist.

PMID- 11992834
TI  - Utility of PSA doubling time in follow-up of untreated patients with localized
      prostate cancer.
AB  - OBJECTIVES: To evaluate the prostate-specific antigen (PSA) changes and the
      ability of PSA doubling time (PSADT) to predict disease progression in untreated
      patients with clinically localized prostate cancer. METHODS: A total of 104
      patients with localized prostate cancer were followed up expectantly with serial
      PSA measurements and digital rectal examination (DRE). PSADT was calculated by
      linear regression analysis for the 94 patients who had a minimum of three PSA
      measurements and 12 months of follow-up. The median follow-up was 33 months. Of
      the 94 patients, 45 underwent repeat prostate biopsy to evaluate whether tumor
      progression occurred during the observation period. RESULTS: Twenty-seven percent
      of patients had rapid PSADTs (less than 48 months). Only the presence of palpable
      disease on DRE correlated with a PSADT of less than 48 months (P <0.05). However,
      a PSADT of less than 120 months consistently correlated with disease progression
      on DRE and on repeat biopsy, as well as with the presence of clinically
      significant cancer. PSADT did not correlate with the Gleason score. Furthermore,
      patients with a PSADT of less than 48 months did not differ significantly from
      those with a PSADT of 48 to 120 months with regard to Gleason score, disease
      progression on DRE or on repeat biopsy, and the presence of significant cancer.
      CONCLUSIONS: A PSADT of less than 120 months correlates with disease progression.
      However, its clinical utility remains limited to identify patients at risk of
      disease progression reliably.

PMID- 11992835
TI  - Extracorporeal shock wave therapy in the treatment of Peyronie's disease:
      experience with standard lithotriptor (siemens-multiline).
AB  - OBJECTIVES: To assess in a prospective study whether extracorporeal shock wave
      therapy (ESWT) using a standard radioscopic location lithotriptor is effective in
      the treatment of Peyronie's disease. METHODS: Fifty-four patients were included
      in this prospective study. Before and after treatment, the angulation was
      calculated by auto-photography. Pain severity was assessed by a visual analog
      pain scale. A self-evaluation questionnaire (International Index of Erectile
      Function) was used. All patients had symptoms (35 had pain during erection and 51
      angulation greater than 20 degrees ). The mean disease duration was 16 months.
      The mean angulation before treatment was 48 degrees (range 10 degrees to 100
      degrees ). Twenty-four patients had erectile dysfunction (questionnaire score
      less than 18). The Multiline Siemens lithotriptor was used. The plaque was
      located by palpation, and 1 mL of contrast agent was injected. Scopic
      visualization was used. Each patient received a minimum of one session of ESWT
      (3000 shock waves, 7 kJ) applied to a flaccid penis. RESULTS: All patients
      completed the protocol. The tolerance and safety were excellent. Of the 35
      patients with pain on erection, 31 (91%) noticed relief immediately after ESWT
      (mean reduction 2.9 on the visual analog pain scale) (P <0.00001). For 29
      patients (53.7%), an improvement in angulation (greater than 10 degrees ) was
      observed, with a mean reduction of 31 degrees (P <0.001). For patients with
      erectile dysfunction, only 6 (25%) had an increased questionnaire score (greater
      than 4). Twenty-five patients thought the plaque was smoother. CONCLUSIONS: ESWT
      with a standard lithotriptor (without the mobile arm) in Peyronie's disease is a
      feasible, safe, and effective treatment for pain on erection and significantly
      improves the penile angle.

PMID- 11992836
TI  - Follow-up functional radiographic studies are not mandatory for all patients
      after ureteroscopy.
AB  - OBJECTIVES: To evaluate the usefulness of follow-up radiographic studies after
      ureteroscopy by retrospective chart review. METHODS: We reviewed the charts of
      118 patients who underwent 134 ureteroscopic procedures from January 1998 to
      November 1999. RESULTS: Follow-up was obtained at our institution for 87
      patients. The follow-up period ranged from 3 to 34 weeks (mean 7, SE +/- 0.75).
      Of 10 patients who underwent ureteroscopy for diagnostic purposes, none had
      postoperative pain or obstruction on follow-up radiographic studies. Of 77
      patients who underwent ureteroscopy for calculi, 12 (16%) had postoperative
      obstruction. One third of patients with residual obstruction (4 of 12) complained
      of persistent pain versus 6% of patients without evidence of obstruction (4 of
      65) (P = 0.02). Twelve patients had residual stone fragments on their follow-up
      radiographic studies; 5 (42%) of these patients complained of pain versus 3 (5%)
      of 65 patients who were stone free after surgery (P = 0.002). The use of pain to
      predict either obstruction or residual fragments had a negative and positive
      predictive value of 83% and 75%, respectively. Preoperative obstruction and
      postoperative pain were combined as one indicator for the presence of residual
      fragments and postoperative obstruction. Patients who had preoperative
      obstruction and presented with postoperative pain had a 67% chance of having
      residual fragments and a 50% chance of residual obstruction, and 96% of patients
      without preoperative obstruction and no postoperative pain had no persistent
      obstruction or residual fragments (P = 0.001). CONCLUSIONS: For patients who
      present for ureteroscopy with no obstruction and report no pain at follow-up, a
      plain radiograph may be sufficient. For patients who present with obstruction and
      report pain during follow-up, functional imaging studies are recommended.

PMID- 11992837
TI  - Prospective comparison of hand-assisted laparoscopic devices.
AB  - OBJECTIVES: To evaluate and compare the three commercially available first
      generation hand-assisted laparoscopic (HAL) devices in a prospective, randomized
      fashion. HAL nephrectomy has become an increasingly popular surgical modality.
      METHODS: Sixty-seven board-certified urologists each performed two HAL
      nephrectomies in a porcine laboratory, using two different hand devices, at a
      learning course sponsored by the American Urological Association. At the
      completion of the laboratory session, each surgeon was asked to complete a 12
      question survey designed to evaluate the different hand-assist devices. RESULTS:
      Thirty-nine surgeons used the HandPort, 47 used the Intromit, and 47 used the
      Pneumosleeve. No statistical differences were found in the ratings among the
      three devices within any category. No device scored better than 8.1 in any
      category, and the overall satisfaction was less than 7.7 in all three groups.
      Although not statistically significant, the Intromit device had the highest
      ratings in the following categories: instructions, maintenance of
      pneumoperitoneum, exchange of laparotomy pads, retrieval of specimens,
      sturdiness, and overall satisfaction. The HandPort had the highest failure rate.
      CONCLUSIONS: HAL relies heavily on devices that allow the hand to be introduced
      into the laparoscopic environment. The three available devices are all effective,
      yet each have their specific advantages and disadvantages. In terms of overall
      satisfaction, no device scored greater than 7.7. The results of this study
      suggest that the need for improvement by all three manufacturers is significant
      and have helped to better identify these areas.

PMID- 11992838
TI  - Minimal incision living donor nephrectomy: improvement in patient outcome.
AB  - OBJECTIVES: To analyze the minimal incision living donor (MILD) nephrectomy and
      compare it with the standard open donor (SOD) nephrectomy with respect to
      incision size, operative time, complication rate, length of hospital stay, and
      recipient creatinine. METHODS: Forty-five consecutive patients who underwent MILD
      nephrectomy were compared with 13 patients who had previously undergone SOD
      nephrectomy. The MILD nephrectomy was performed through a minimally invasive
      incision using a modified, anterolateral, retroperitoneal approach without a rib
      resection. The incision length, operative time, complication rates, length of
      hospital stay, and recipient creatinine were analyzed. RESULTS: The average
      incision length in the MILD group was 8.6 cm compared with 21.8 cm in the SOD
      group (P >0.005.) The operative times (209 minutes in the MILD group versus 191
      minutes in the SOD group) were not significantly different. Four postoperative
      complications were encountered in the SOD group and seven in the MILD group. The
      average hospital stay for the MILD patients was 2.5 days compared with 4.6 days
      in the SOD group, and as the procedure was refined, the length of stay was
      reduced to 1 day in 3 patients. The recipient creatinine at 1 and 6 months was
      1.39 and 1.4 mg/dL in the MILD group, respectively. CONCLUSIONS: The MILD
      nephrectomy allows the patient to undergo a less morbid procedure with a more
      aesthetic incision. Patients have fewer complications, minimal anesthesia
      exposure, and short hospital stays.

PMID- 11992839
TI  - Incidental appendectomy during radical cystectomy--is it necessary?
AB  - OBJECTIVES: To evaluate the rationale behind incidental appendectomy during
      radical cystectomy. Incidental appendectomy during radical cystectomy is done to
      avoid the morbidity due to the future development of appendicitis and an
      additional operation. METHODS: We performed a retrospective review of 105
      patients who underwent radical cystectomy during an 8-year period (1986 to 1993).
      Appendectomy was incorporated in the initial 40 radical cystectomies and was
      avoided in the next 65 radical cystectomies. RESULTS: We had a median follow-up
      of greater than 10 years in patients who underwent appendectomy along with
      radical cystectomy and of more than 7 years in patients in whom appendectomy was
      avoided. None of the patients from either group had any complication related to
      the appendicular pathologic findings. CONCLUSIONS: The data from this study
      suggest that no advantage exists in persisting with incidental appendectomy
      during radical cystectomy.

PMID- 11992840
TI  - Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan.
AB  - OBJECTIVES: Unusually high incidences of upper urinary tract urothelial carcinoma
      (UUT-UC) have been reported from the endemic area for "blackfoot disease" of
      southern Taiwan, and the arsenic-contaminated water was considered to be the
      reason for this prevalence. In this study, we determined the ratio of UC in
      different locations, the difference in clinical profiles for UUT-UC and urinary
      bladder urothelial carcinoma (UB-UC), and the influence of tumor location on
      survival in a medical center of northern Taiwan. METHODS: A total of 535 patients
      with pathologically proven UC were reviewed retrospectively in this study, and
      clinical data were recorded from pathologic and chart reviews. Statistical
      analyses to determine the association between tumor location and clinical
      variables, and stratified survival analyses to determine the effect of tumor
      location on survival were performed. RESULTS: The incidence of UUT-UC was
      relatively high (the ratio of renal pelvis/ureter/urinary bladder was
      1:2.08:6.72), even though most of the patients did not reside in the endemic
      "blackfoot disease" area. Young age, female sex, higher T stage, and elevated
      pretreatment serum lactate dehydrogenase and creatinine level were significantly
      associated with UUT-UC after multivariate logistic regression analysis. Tumor
      location influenced survival in patients with early-stage disease or favorable
      prognostic factors. CONCLUSIONS: Factors other than arsenic water contamination
      may contribute to the unusually high incidence of UUT-UC in the non-"blackfoot
      disease" area in Taiwan. UUT-UC carried a more aggressively clinical behavior
      than UB-UC; tumor location influences patient survival markedly in patients with
      early-stage disease or favorable prognostic factors.

PMID- 11992841
TI  - Combined cystolithotomy and transurethral resection of prostate: best management
      of infravesical obstruction and massive or multiple bladder stones.
AB  - OBJECTIVES: To investigate the results of combined suprapubic cystolithotomy
      followed by transurethral resection (TUR) of the prostate (TURP) or TUR of the
      bladder neck in patients with infravesical obstruction and massive or numerous
      bladder stones. We also reviewed the medical literature and compared the success,
      morbidity, and mortality rates of the treatment modality presented here and the
      nonsurgical modality of transurethral lithotripsy and resection of the prostate
      or bladder neck. METHODS: Through a 10-year period, 20 men with benign prostatic
      hyperplasia or bladder neck obstruction and massive or numerous bladder stones
      underwent cystolithotomy for stone clearance followed by TURP or TUR of the
      bladder neck. A second group of 20 randomly selected men who underwent TURP alone
      was studied retrospectively for time of surgery, number of days of postoperative
      indwelling catheter use, and hospital stay. RESULTS: No deaths occurred. All
      stones were successfully evacuated (100% stone-free rate). The operative time and
      number of days of postoperative indwelling catheter use and hospital stay were
      notoriously shorter in the present series compared with the transurethral
      lithotripsy and TURP modality. A single case of fever (5% complication rate)
      occurred in each group. When comparing the data of the present series with a
      group of 20 men who underwent TURP only, no differences were found in the times
      of postoperative indwelling catheter use and hospital stay. Cystolithotomy
      performed before TURP prolonged the total time of surgery an average of 18.4
      minutes. CONCLUSIONS: In the era of endoscopic and minimally invasive surgery, a
      small suprapubic cystostomy followed by TURP is still the treatment of choice in
      cases of infravesical obstruction and very large or numerous bladder stones. The
      procedure is quick and easy to perform and bears a low morbidity rate compared
      with transurethral lithotripsy and TURP. A small cystotomy does not prolong the
      time of indwelling catheter use and hospital stay.

PMID- 11992842
TI  - Anterior distribution of Stage T1c nonpalpable tumors in radical prostatectomy
      specimens.
AB  - OBJECTIVES: To determine the anatomic patterns of tumor distribution in radical
      prostatectomy specimens from nonpalpable prostate cancer. METHODS: Tumor maps
      directly traced from histologic slides of 62 radical prostatectomy specimens were
      superimposed by a computer-assisted imaging technique to create an idealized
      prostate gland at three levels: apex, mid-prostate, and base. To investigate
      specific patterns of tumor distribution, the sites of tumor in each quadrant were
      compared according to risk group stratification. The tumor extent was compared
      with the patterns of positivity in routine sextant biopsies. RESULTS: Among all
      patients, the tumor frequency was 85.5% in the mid-gland, 82.3% in the apex, and
      48.4% in the base. Analysis by quadrant showed that tumors were significantly
      denser in the apex to mid-prostate. The primary extent of these tumors appeared
      to lie predominantly in the anterior half of the gland. Biopsy yields at the apex
      and mid-prostate appeared low compared with the frequency of cancers at these
      levels. No patterns specific to the different risk groups were found, but no
      tumors within the anterior base were found in the low-risk group. CONCLUSIONS:
      The primary extent of nonpalpable tumors appeared to lie predominantly in the
      anterior half of the gland at the apex to mid-prostate levels. Additional biopsy
      cores taken from more anterior regions of the gland may enhance the detection of
      nonpalpable cancers further.

PMID- 11992843
TI  - Needle core length in sextant biopsy influences prostate cancer detection rate.
AB  - OBJECTIVES: Prostate cancer detection in biopsies increases with the number of
      sites and total tissue sampled. Its dependence on needle core fragment length is
      uncertain. METHODS: We surveyed two consecutive series of sextant needle biopsies
      from two practices in 1998 to 2000: 251 patients from Pennsylvania (group P) and
      1596 from Virginia (group V). We tabulated the gross needle core lengths per
      sextant site and classified the diagnoses as benign or into four nonbenign
      categories: high-grade prostatic intraepithelial neoplasia; atypical small acinar
      proliferation, suspicious; atypical small acinar proliferation, suspicious plus
      high-grade prostatic intraepithelial neoplasia; and cancer. Logistic regression
      analysis was used to correlate cancer or a nonbenign diagnosis with the total
      length (sum of six sites) and, after excluding the sites with more than one core,
      with the length per single core, and the anatomic site of origin (apex, mid
      gland, base). RESULTS: The mean total tissue length sampled was 108 +/- 27 mm
      (range 30 to 275) in group P and 81 +/- 22 mm (range 30 to 228) in group V.
      Sextant sites with a single core contained a mean of 12.8 +/- 3.5 mm tissue, with
      a 3.6-fold variation among the middle 95%. Group V core lengths at the apex
      averaged 11.8 mm, shorter (P = 0.0001) than mid (13.3 mm) or base (12.7 mm). A
      predictive value of longer length for a nonbenign diagnosis was noted in four of
      six sextants (P <0.04), with trend strongest at the apex, for which detection was
      influenced by abnormal digital rectal examination (P = 0.02) or ultrasound (P =
      0.04) findings. CONCLUSIONS: The length of single cores sampled by sextant biopsy
      can vary more than 3.6-fold and represents a quality assurance consideration. The
      effect of length on cancer or nonbenign detection was maximal at the prostatic
      apex where the cores were shortest.

PMID- 11992844
TI  - Percentage of core lengths involved with prostate cancer: does it add to the
      percentage of positive prostate biopsies in predicting postoperative prostate
      specific antigen outcome for men with intermediate-risk prostate cancer?
AB  - OBJECTIVES: To evaluate whether the percentage of core lengths involved with
      prostate cancer added clinically significant information concerning the time to
      postoperative prostate-specific antigen (PSA) failure in the intermediate-risk
      patient beyond what is provided by the percentage of positive biopsies. METHODS:
      Cox regression multivariable analysis was performed to compare the ability of the
      two measurements of biopsy cancer volume to predict the time to PSA failure from
      a series of 184 surgically treated intermediate-risk patients. PSA outcome was
      estimated using the actuarial method of Kaplan and Meier, and comparisons were
      made using the log-rank test. RESULTS: Both the percentage of core lengths
      involved with prostate cancer (P = 0.01) and the percentage of positive biopsies
      (P = 0.002) were significant predictors of the time to PSA failure on univariable
      analysis. The 4-year PSA outcome was 83% versus 47% (P = 0.0008) and 83% versus
      53% (P = 0.007) for the percentage of positive biopsies stratified by 50% or less
      versus greater than 50% and the percentage of core lengths involved with prostate
      cancer stratified by 25% or less versus greater than 25%, respectively. However,
      only the percentage of positive biopsies remained significant (P = 0.03) on
      multivariable analysis. CONCLUSIONS: The percentage of core lengths involved with
      prostate cancer did not provide additional clinically relevant information to the
      percentage of positive biopsies for patients with intermediate-risk prostate
      cancer. Therefore, the routine measurement of core involvement may not be
      necessary in this patient population.

PMID- 11992845
TI  - Utility of intraoperative frozen section analysis of surgical margins in region
      of neurovascular bundles at radical prostatectomy.
AB  - OBJECTIVES: To report our experience with intraoperative frozen section (IFS)
      analysis in patients who are potential candidates for nerve-sparing surgery.
      Potency can be maintained in select patients who undergo radical prostatectomy
      using a nerve-sparing approach. However, extracapsular disease extension in the
      area of the neurovascular bundles may compromise adequate surgical margins in
      some patients undergoing such surgery. METHODS: We reviewed the pathologic
      results from 101 patients who underwent either unilateral or bilateral nerve
      sparing radical prostatectomy in whom IFS analysis was performed. The clinical
      disease stage was T1 in 20 patients and T2 in 81 patients. The mean serum
      prostate-specific antigen level before surgery was 7.2 ng/mL. Of the 101
      patients, 62, 28, and 11 had a biopsy Gleason score of 2 to 6, 7, and 8 to 10,
      respectively. IFS analysis was performed on the surgical margin thought to be at
      risk of tumor involvement as determined by the results of systematic prostate
      biopsy, transrectal ultrasonography, or intraoperative inspection. If the frozen
      section was positive, additional tissue, including the neurovascular bundle, was
      subsequently removed to establish clear surgical margins. IFS results were
      compared with those on the final, permanent tissue section, as well as with the
      status of the additionally resected tissue. RESULTS: The IFS results were
      identical to those obtained on the final, permanent section in 92 (91%) of the
      101 cases. The IFS results showed positive margins in 15 (15%) of 101 patients.
      Of these cases, 11 demonstrated positive margins on the final permanent sections.
      Of the 86 patients with negative frozen section diagnosis, 5 had positive
      surgical margins on permanent sections at the site of the IFS. The positive and
      negative predictive value for the IFS technique was 73% and 94%, respectively. Of
      the 15 patients with positive IFS, 12 (80%) had no evidence of tumor in the
      additionally resected tissue. Prostate-specific antigen recurrence was noted in
      7% of the study population. The risk of recurrence in patients with either
      positive or negative IFS findings was similar. CONCLUSIONS: IFS at the time of
      radical prostatectomy can reliably predict the final surgical margin status in
      most carefully selected high-risk patients when there are concerns about the
      margin status.

PMID- 11992846
TI  - Prognostic value of DNA ploidy and nuclear morphometry in prostate cancer treated
      with androgen deprivation.
AB  - OBJECTIVES: To assess the prognostic value of flow cytometry and nuclear
      morphometry in prostate cancer after androgen deprivation treatment. METHODS: A
      total of 127 patients with a prostate cancer diagnosis who had undergone androgen
      suppression were retrospectively studied. The DNA content by flow cytometry and
      nuclear morphometry was studied from biopsy specimens. In the patients with Stage
      M0, two multivariate analyses by the Cox proportional regression model were
      performed to determine whether the experimental variables (DNA content and
      nuclear area) added independent information to the classic prognostic factors
      (Gleason score and stage). Using the statistical analysis results, risk groups
      were created. RESULTS: T and M categories, Gleason score, DNA ploidy, and mean
      nuclear area proved to have prognostic value in the univariate analysis. For the
      group of patients free of metastasis (M0), it was possible to create low,
      intermediate, and high-risk groups using stage and Gleason score with
      statistically significant differences in survival. Multivariate analysis,
      combining the classic and experimental variables, selected Gleason score and DNA
      content as prognostic independent factors. Also, risk groups with statistically
      significant differences in survival were created. However, the net result of
      combining both kinds of factors was at least as valuable as the combination of
      stage and Gleason score in predicting survival. CONCLUSIONS: The determination of
      DNA ploidy and mean nuclear area do not add enough independent information to
      improve the predictive value to justify their use in this group of patients
      treated with hormonal therapy.

PMID- 11992847
TI  - Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic
      lymphadenectomy compared with nomogram prediction of metastasis.
AB  - OBJECTIVES: To compare the sensitivity and negative predictive values of frozen
      section analysis of pelvic lymphadenectomy in patients undergoing radical
      retropubic prostatectomy for prostate adenocarcinoma with the predictive power of
      published nomograms for metastasis to lymph nodes. METHODS: A retrospective
      review was performed on all patients who underwent bilateral pelvic
      lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma
      between 1991 and early 1997. The sensitivity and negative predictive values were
      computed comparing frozen section analysis, and patients were grouped by risk
      stratification. Comparison was made using the McNemar text. RESULTS: The
      sensitivity for detecting lymph node metastasis on frozen section analysis for
      all risk groups was 33% (9 of 27). The sensitivity for identifying patients at
      high risk of having nodal metastasis by published nomograms alone was 67% (18 of
      27) (P = 0.04). The overall negative predictive value for frozen section analysis
      was 96.5% (503 of 521). The negative predictive value for uninvolved lymph nodes,
      using low and intermediate-risk groups stratified by published nomograms, was
      97.9% (436 of 445). CONCLUSIONS: Frozen section analysis of pelvic lymph nodes to
      detect metastatic prostate adenocarcinoma is less sensitive in determining which
      patients will have lymph nodes involved by metastatic adenocarcinoma than using
      risk stratification by published nomograms. The negative predictive value of
      frozen section analysis in all risk groups was very high, up to 97.9%.

PMID- 11992848
TI  - Salvage radiotherapy after radical prostatectomy for prostate adenocarcinoma:
      analysis of efficacy and prognostic factors.
AB  - OBJECTIVES: To determine the probability of biochemical control for patients
      treated with salvage irradiation and identify prognostic factors associated with
      successful salvage. The optimal management of prostate cancer in patients with an
      elevated prostate-specific antigen (PSA) level after radical prostatectomy
      remains unclear. METHODS: We reviewed the records of 54 patients with node
      negative prostate cancer treated with radiotherapy alone between 1991 and 1998
      for isolated biochemical relapse after prostatectomy. The median preoperative PSA
      level was 15 ng/mL, and the median salvage PSA level was 1.3 ng/mL. Complete
      pathologic information was recorded, as was the interval to postoperative PSA
      failure. Radiotherapy was delivered to the prostatic fossa using appropriate
      techniques. The primary endpoint was biochemical failure, measured from
      radiotherapy initiation to the first detectable PSA level. Biochemical control
      rates were determined using Kaplan-Meier methods. The median follow-up was 45
      months. RESULTS: The initial complete response rate was 76%. Only seminal vesicle
      status demonstrated borderline significance for the rate of the initial complete
      response. The 5-year actuarial biochemical control rate was 35%. The presence of
      seminal vesicle invasion, Gleason score greater than 6, and an immediately
      detectable postoperative PSA level all predicted for decreased 5-year biochemical
      control. Gleason score and detectable postoperative PSA retained significance on
      multivariate analysis. Those with a salvage PSA level of 1.2 ng/mL or less had a
      trend toward a decreased 5-year biochemical control rate (P = 0.07). CONCLUSIONS:
      Salvage radiotherapy yields a 76% complete response rate, with 35% of treated
      patients free of a detectable PSA at 5 years. Those with favorable biochemical
      and pathologic tumor features are most likely to remain disease free.

PMID- 11992849
TI  - Postprostatectomy radiotherapy for high-risk prostate cancer.
AB  - OBJECTIVES: To assess the biochemical and clinical results of postprostatectomy
      radiotherapy (RT) for high-risk, mostly non-rgan-confined prostate cancer.
      METHODS: After radical prostatectomy, 66 consecutive patients received either
      adjuvant (n = 29) or therapeutic (n = 37) postoperative RT. Therapeutic RT was
      given for persistently elevated postoperative prostate-specific antigen (PSA)
      levels (n = 14), gradually rising PSA levels (n = 6), or clinical local
      recurrence (n = 17). The selection of time and referral for RT was at the
      discretion of the treating urologists. RESULTS: The mean and median follow-up
      after surgery was 56.8 and 54.2 months, and after radiotherapy, it was 43.2 and
      35.0 months, respectively. At 5 years, the actuarial biochemical control for the
      whole collective was 59.7% (95% confidence interval [CI] 43.3% to 72.8%).
      Patients treated with adjuvant RT had statistically improved biochemical control
      (85.2% versus 34.0%, P = 0.001), but not disease-free survival (91% versus 73%, P
      = 0.09). Advanced tumor stage (pT3b-4) (relative risk 16.6; 95% CI 0.9 to 313.3;
      P = 0.01), poorly differentiated histologic features (relative risk 4.63; 95% CI
      1.8 to 12.2; P = 0.001), and pre-RT PSA (relative risk 1.15, 95% CI 1.06 to 1.25;
      P = 0.003) were associated with a statistically significant increased risk of
      biochemical failure. CONCLUSIONS: Although adjuvant postoperative RT resulted in
      improved biochemical control, no significant difference in disease-free survival
      has been obtained to date. It therefore remains to be determined whether the
      better biochemical control observed will ultimately translate into a survival
      benefit after longer follow-up and prospective trials.

PMID- 11992850
TI  - Preoperative parameters for predicting early prostate cancer recurrence after
      radical prostatectomy.
AB  - OBJECTIVES: To determine whether easily measurable prostate biopsy features could
      complement Gleason score, prostate-specific antigen (PSA), or clinical stage in
      predicting recurrence-free survival after prostatectomy. Information relating
      preoperative parameters to recurrence-free survival is needed to counsel patients
      with newly diagnosed prostate cancer regarding expectations for postprostatectomy
      cancer control. METHODS: The data of a cohort of 588 consecutive prostatectomy
      patients (median age 61 years, range 39 to 83) with ascertained preoperative data
      and up to 4 years of postprostatectomy follow-up were analyzed. Bivariate and
      multivariate Cox proportional hazards analysis evaluated preoperative factors
      (clinical stage, PSA, biopsy Gleason score, greatest percentage of a biopsy core
      involved by cancer [GPC], number of biopsy cores containing cancer, perineural
      invasion) to identify those relating significantly to recurrence-free survival.
      Functional forms of these factors were evaluated to optimize accuracy in
      predicting cancer control. RESULTS: The baseline parameters significantly
      affecting PSA-free survival included PSA level (P <0.01), biopsy Gleason score (P
      = 0.04), and GPC (P <0.01). Although clinical stage and perineural invasion had a
      marginal association with PSA-free survival as univariate factors, this
      association was not independently significant in multivariable analysis. The
      multivariate Cox model using PSA, Gleason score, and GPC was highly predictive of
      PSA free-survival (chi-square = 48.2, P = 0.0001). A set of plots representing
      these data can be used to identify the risk of early postoperative PSA recurrence
      on the basis of specific preoperative PSA, Gleason score, and GPC values.
      CONCLUSIONS: These findings provide a highly significant model and a simple tool
      for assisting preoperative patient counseling regarding predicted cancer control
      after radical prostatectomy.

PMID- 11992853
TI  - Effects of sildenafil citrate (viagra) on blood pressure in normotensive and
      hypertensive men.
AB  - OBJECTIVES: To determine the occurrence of clinically significant decreases in
      blood pressure (BP) with sildenafil use in normotensive and hypertensive men by
      means of ambulatory BP monitoring. METHODS: On 2 nights, 49 men (22 hypertensive,
      27 normotensive) had their ambulatory systolic BP (SBP), diastolic BP (DBP), and
      heart rate monitored during the first 3 hours (waking period) and every 30
      minutes after midnight for 3 additional hours (sleeping period). No medication
      was taken on one night; sildenafil 100 mg was taken on the other. RESULTS:
      Sildenafil decreased SBP (-6.0 mm Hg; P = 0.0003), DBP (-4.5 mm Hg; P = 0.001),
      and mean arterial pressure (-5.3 mm Hg; P = 0.00008). The BP-lowering effects of
      sildenafil did not differ significantly in the normotensive and hypertensive men.
      Age significantly affected the BP reductions; decreases in SBP, DBP, and mean
      arterial pressure were greater in men 49 years old and older than in those
      younger than 49 years old. According to readings averaged over the entire control
      and treatment periods, 22.7% of hypertensive men and 3.7% of normotensive men
      experienced SBP reductions of 20 mm Hg or greater (P = 0.08 for comparison of the
      two groups); the respective values for DBP were 9.1% and 3.7% (P not
      significant). These reductions were not associated with any hypotensive symptoms.
      All participants tolerated sildenafil well. CONCLUSIONS: Sildenafil caused small,
      clinically insignificant reductions in ambulatory BP in active and resting
      normotensive and hypertensive men. The results of this study suggest that, when
      used in accordance with the prescribing information and current treatment
      guidelines, sildenafil should be safe in younger and older men with or without
      hypertension.

PMID- 11992854
TI  - Community-based study of erectile dysfunction and sildenafil use: the Rancho
      Bernardo study.
AB  - OBJECTIVES: To evaluate erectile dysfunction (ED) using a validated self
      administered 5-item questionnaire (5-item version of the International Index of
      Erectile Function [IIEF-5]) and the use of sildenafil in community-dwelling older
      men. METHODS: In October 1998, the IIEF-5 was mailed to all surviving members of
      an established community-based cohort of older men. The degree of ED was
      stratified by the erectile function domain score as complete (4 or less), severe
      (5 to 10), moderate (11 to 14), mild (15 to 18), or none (19 to 20). Men were
      also asked about sildenafil use and its effectiveness. RESULTS: A total of 976
      men (64%) responded to the questionnaire. The internal consistency of the
      questionnaire construct was confirmed, with a Cronbach's alpha coefficient of
      0.96 for all 5 questions. Eighty-nine percent of men younger than 50 years were
      sexually active compared with 37% of men older than age 80. Twenty-six percent of
      sexually active men reported complete (3%), severe (10.5%), or moderate (12.6%)
      ED. The prevalence of moderate or complete ED increased with age and was reported
      by 58% of men aged 75 to 79 years. Eleven percent of sexually active men had used
      sildenafil one or more times, with 63% reporting good or "terrific" effects and
      11% reporting no benefit. The response to sildenafil deteriorated with age and
      increasing degree of ED. CONCLUSIONS: The results of this community-based study
      confirm the strong correlation between advancing age and the prevalence and
      degree of ED, with 33% of men aged 75 and older reporting at least moderate ED.
      Nevertheless, more than 33% of men older than 75 years remained sexually active.
      Of the 660 sexually active men, 81% reported satisfaction with sexual
      intercourse; only 11% had tried sildenafil.

PMID- 11992855
TI  - Topical mitomycin C for extensive, recurrent conjunctival-corneal squamous cell
      carcinoma.
AB  - PURPOSE: To evaluate the efficacy of topical mitomycin C for extensive recurrent
      conjunctival and corneal squamous cell carcinoma (SCC). DESIGN: Interventional
      case series. METHODS: A prospective study was conducted in a single institution.
      Ten patients (ten eyes) with extensive recurrent conjunctival and corneal SCC
      were studied. The patients received topical mitomycin C 0.04% one drop four times
      daily in the eye with SCC. Treatment cycles were defined as 1 week using
      medication followed by 1 week without medication. Such treatment cycles were
      repeated until resolution of the conjunctival malignancy was clinically evident.
      The main outcome measures were tumor response and medication-related
      complications. RESULTS: Of the ten patients, the median age was 66 years (range
      33-77 years). Before referral, the patients had undergone a median of two
      previous conjunctival tumor resections revealing the diagnosis of in situ SCC in
      three cases and locally invasive SCC in six cases. At presentation, the tumor
      involved the limbus and cornea in all ten eyes, forniceal conjunctiva in three
      eyes, and tarsal conjunctiva in one eye. The extensive tumor affected a median of
      10 clock hours of limbal conjunctiva and 10 clock hours of cornea, with corneal
      epithelial invasion for a median of 50% (range 20%-100%) of its surface.
      Mitomycin C 0.04% four times daily was applied for a median of three cycles
      (range 1-4 cycles). Complete tumor regression was documented in all ten cases
      (100%). There was no recurrence over a mean follow up of 22 months (range 6-50
      months). Mitomycin C caused moderate temporary local irritation and conjunctival
      erythema and chemosis, but no long-term intraocular or extraocular complications.
      CONCLUSIONS: Based on this small series, topical mitomycin C 0.04% appears to be
      a safe and effective therapy for conjunctival or corneal SCC, even when there is
      extensive recurrent tumor.

PMID- 11992856
TI  - Complexity of contact lens fitting after refractive surgery.
AB  - PURPOSE: To quantify and describe the complexity of contact lens correction on
      corneas altered by refractive surgery. DESIGN: A case-control study involving
      postrefractive surgery patients and controls from one multidisciplinary contact
      lens practice. METHODS: The contact lens care of one randomly selected eye of 30
      postrefractive surgery patients (15 postincisional and 15 postlamellar refractive
      surgery cases) was retrospectively analyzed and compared with that of 30 age-and
      gender matched nonrefractive surgery controls. We quantified the complexity by
      the number of diagnostic lenses used to establish the initial lens order, the
      number of ordered lenses required to complete the fit, and the number of office
      visits during the first 4 months of lens care. Final contact lens optical powers,
      corrected visual acuities, complications, and lens success/failure were also
      studied. The nonparametric Mann-Whitney U test was used for statistical analysis.
      RESULTS: Postrefractive surgery eyes utilized statistically more diagnostic
      lenses (P =.048), ordered lenses (P =.008), and office visits (P <.0001). There
      were no statistical differences in the number of office visits, number of
      diagnostic contact lenses used, and number of ordered contact lenses between the
      postincisional and postlamellar refractive surgery patients. Although final
      contact lens optical powers were not significantly different (P =.06) between the
      two groups, contact lens corrected LogMAR acuities were statistically worse (P
      =.013) in the postrefractive surgery eyes than in the control group. Contact lens
      failures occurred in four postrefractive surgery eyes, while no eyes in the
      control group failed to tolerate contact lenses. CONCLUSIONS: Corneas altered by
      either incisional or lamellar refractive surgery techniques are more challenging
      to fit with contact lenses than nonsurgically altered eyes, requiring more lenses
      and chair time, while resulting in slightly poorer contact lens corrected visions
      and more failures.

PMID- 11992857
TI  - The Heidelberg Retina Tomograph vs clinical impression in the diagnosis of
      glaucoma.
AB  - PURPOSE: To compare the sensitivity and the specificity of the Heidelberg Retina
      Tomograph (HRT) classification of "Glaucoma" or "Normal" with that derived from
      clinical impression (CI) based on several parameters. DESIGN: Consecutive
      observational case series. METHODS: In a retrospective chart review of 200 left
      eyes of 200 consecutive patients referred to the Glaucoma Service Diagnostic
      Laboratory of the Wills Eye Hospital, we compared the HRT-based classification of
      "Glaucoma" or "Normal" with a CI classification of "Definite glaucoma," "Probably
      glaucoma," "Probably no glaucoma," and "No glaucoma." RESULTS: The HRT-based
      diagnosis of "Glaucoma" or "Normal" had an 86% sensitivity and 68% specificity
      when compared with a clinical impression (CI) of "Definite glaucoma," used as a
      strict gold standard definition of glaucoma; an 83% sensitivity and 57%
      specificity when the CI "Definite glaucoma" and "Probably glaucoma" were combined
      as a more liberal definition of glaucoma; a 76% sensitivity and 69% specificity
      when the CI "Definite glaucoma," "Probably glaucoma," and "Probably no glaucoma"
      were combined as the most liberal definition of glaucoma. The HRT diagnosis had
      an 86% sensitivity and 51% specificity when compared with the groups "Probably
      glaucoma," "Probably no glaucoma," and "No glaucoma" combined and considered as
      no glaucoma. CONCLUSIONS: In this study, HRT-based classification of "Glaucoma"
      or "Normal" was moderately sensitive, but not very specific when compared with
      the clinical impression as the gold standard. Clinicians should not rely on the
      HRT diagnosis alone, but should use it to supplement the impression based on an
      eye examination and other ancillary tests.

PMID- 11992858
TI  - Goniotomy for glaucoma secondary to chronic childhood uveitis.
AB  - PURPOSE: To evaluate the safety and efficacy of standard goniotomy surgery for
      young patients with refractory glaucoma associated with chronic childhood
      uveitis. DESIGN: Interventional case series. METHODS: We retrospectively reviewed
      all goniotomies performed at our institution for patients with a diagnosis of
      refractory glaucoma associated with chronic childhood uveitis from 1994 to 2000
      (this was our first-line surgery for such patients during these years). Uveitis
      was medically controlled in all cases for at least 6 weeks before surgery. The
      main outcome measure was time after surgery without failure. Success was defined
      as final intraocular pressure (IOP) <or= 21 mm Hg after one or two goniotomies
      without need for further surgical intervention. Follow-up was >or=6 months or
      until surgical failure. RESULTS: Nineteen goniotomies were performed on 16 eyes
      (12 patients). Diagnoses included uveitic glaucoma associated with juvenile
      rheumatoid arthritis, sarcoidosis, and idiopathic uveitis. The mean patient age
      at first goniotomy was 15.3 years (range, 6.5-30), with mean follow-up 32.4
      months (range, 6-84). Cases included were phakic (10 eyes), aphakic (four eyes),
      and pseudophakic (two eyes). The mean preoperative IOP was 32.3 +/- 4.6 mm Hg.
      Surgical success was achieved in 12 of 16 (75%) eyes with a mean postoperative
      IOP of 12 +/- 2.5 mm Hg for these eyes (mean IOP reduction, 20.0 mm Hg, P
      <.0001). In 10 of 16 eyes (60%), surgical success was achieved after a single
      goniotomy. Uveitis was stable in all patients after the early post-operative
      period. Successful eyes used, on average, 1.4 +/- 1.1 glaucoma medications after
      goniotomy. Complications were mild and included transient hyphema in nine cases
      (56%) and worsening of a preexisting cataract in a single case (6%). CONCLUSIONS:
      Goniotomy represents a safe and effective first-line surgery for young patients
      with refractory glaucoma associated with chronic uveitis, although the majority
      of patients require glaucoma medication after the procedure.

PMID- 11992859
TI  - Birdshot retinochoroiditis: long term follow-up of a chronically progressive
      disease.
AB  - PURPOSE: To determine the long-term course of birdshot retinochoroiditis by
      reviewing patient records from The University of Iowa Hospitals and Clinics.
      DESIGN: A descriptive case series. METHODS: We conducted a retrospective review
      of 19 patients seen at The University of Iowa for birdshot retinochoroiditis.
      Inclusion criteria were set before review. Goldmann perimetry isopters were
      converted to an area measurement in steradians and the I2e and I4e isopters were
      evaluated at each time point. The visual acuity, electroretinography (ERG), and
      visual field findings were compared to the clinical appearance of the fundus.
      RESULTS: Follow-up ranged from one visit to 220 months. Of the 14 patients who
      were tested, all were HLA-A29-positive. Seven patients were followed for >or=60
      months. Eleven patients were followed for >or=30 months. The initial visual
      acuity was 20/50 or better in 36 of 38 eyes and 20/60 and 20/80 in the remaining
      two. Visual acuity was worse than 20/50 in three of 22 eyes followed for more
      than 30 months. Visual field data demonstrated progressive loss of area for
      either the I4e or I2e isopters in six of seven patients who were followed for
      >or=60 months. Multiple ERGs were performed over time on eight of 19 patients;
      seven of eight patients demonstrated progressive loss of electrophysiologic
      indices. CONCLUSION: Retinal function in birdshot retinochoroiditis deteriorated
      progressively over a period of years despite stable visual acuity. Late in the
      course of disease, visual acuity may be lost due to chorioretinal atrophy in the
      posterior pole. Visual acuity alone is not an adequate parameter with which to
      monitor disease activity and may falsely suggest that a patient is stable or
      doing well. Intermittent treatment of the inflammatory exacerbations did not
      prevent progressive visual loss. Other treatment strategies such as prolonged
      corticosteroid or immunosuppressive treatment should be investigated for patients
      with birdshot retinochoroiditis.

PMID- 11992860
TI  - Retinal detachment after phacoemulsification: a study of 114 cases.
AB  - PURPOSE: To analyze the features of retinal detachment (RD) occurring after
      cataract surgery performed by Kelman phacoemulsification (KPE) and to identify
      any potential correlations between KPE intraoperative complications and the
      features of RD (incidence apart) as well as the final visual outcome. DESIGN:
      Interventional consecutive case series. METHODS: Retrospective review of 114 eyes
      of 114 consecutive patients with RD occurring after KPE and followed for 6 months
      or more after surgery. RESULTS: Removal of posteriorly dislocated lens fragments
      during KPE by pars plana vitrectomy (PPV) was associated with a significantly
      shorter time interval between KPE and RD (3.89 vs. 15.7 months, P =.0044). Once
      RD occurred, no other statistically significant correlation between its features
      or the final visual outcome and KPE intraoperative complications (posterior
      capsular rupture, vitreous loss, posteriorly dislocated lens fragments) was
      detected. The overall anatomic reattachment rate was 94%. Only redetachment
      associated with the development of proliferative vitreoretinopathy (PVR) was
      significantly correlated with ultimate anatomic failure (P =.0036). A best
      corrected visual acuity of 20/60 or better was achieved in 58 out of 114 eyes
      (51%). Three variables were independently correlated with visual results: more
      extensive RD (P =.0001), redetachment associated with the development of PVR (P
      =.0029), and failure to identify retinal breaks (P =.0114). CONCLUSIONS:
      Posterior capsular rupture and vitreous loss during KPE do not seem to affect the
      features (incidence apart) or the final visual outcome of RD occurring
      afterwards, except for a shorter time interval between KPE and RD in eyes that
      underwent PPV to remove posteriorly dislocated lens fragments.

PMID- 11992861
TI  - Polypoidal choroidal vasculopathy: natural history.
AB  - PURPOSE: The present study was performed to clarify the long-term natural history
      of polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective, consecutive
      observational case series. METHODS: Fourteen eyes of 12 consecutive patients with
      PCV were prospectively followed in our clinic for at least 2 years without any
      treatment after a first visit to the clinic between February 1996 and November
      1998. All patients underwent complete ophthalmologic examination, color fundus
      photography, and fluorescein and indocyanine green (ICG) angiography at regular
      intervals. Inclusion criteria were as follows: eyes had serous and/or hemorrhagic
      pigment epithelium detachment (PED) and retinal detachment in the posterior pole,
      and ICG angiography revealed a branching vascular network with polypoidal
      dilations at the terminals of the network. Exclusion criteria were as follows:
      other diseases such as exudative age-related macular degeneration, high myopia,
      angioid streaks, and presumed ocular histoplasmosis syndrome, and patients who
      previously underwent any ocular surgery. RESULTS: Patients were followed for mean
      of 39.9 months (range, 24-54 months). PCV was present in 10 (83%) men and two
      women and in the elderly (mean age 68.1 years), usually unilateral (83%) with
      vascular lesions located at the macula (93%). The PCV manifested in two patterns,
      exudative and hemorrhagic. In the exudative pattern, serous PED and retinal
      detachment were predominant at the macula. The hemorrhagic pattern was
      characterized by hemorrhagic PED and subretinal hemorrhage at the macula. ICG
      angiography revealed polypoidal choroidal neovascularization that was changeable
      in appearance and repeatedly grew and spontaneously regressed, but the vascular
      network persisted. In some eyes, a collection of small aneurysmal dilations of
      vessels resembling a cluster of grapes appeared and all of them had marked
      bleeding and leakage and worse outcome. CONCLUSION: Polypoidal choroidal
      vasculopathy is a long persistent chronic disease and the patients had a variable
      course. Fifty percent of the patients had a favorable course. In the remaining
      half of the patients, the disorder persisted for a long time with occasional
      repeated bleeding and leakage, resulting in macular degeneration and visual loss.
      Eyes with a cluster of grapes-like polypoidal dilatations of the vessels had a
      high risk for severe visual loss.

PMID- 11992862
TI  - Hydroxychloroquine and chloroquine retinopathy: screening for drug toxicity.
AB  - PURPOSE: To report hydroxychloroquine and chloroquine retinopathy and consider
      screening for drug toxicity. DESIGN: Retrospective observational case series.
      METHODS: Review of clinical records, visual fields, fundus photographs, and
      fluorescein angiography of six patients from a retina referral practice. RESULTS:
      All cases arose because of failure by physicians to avoid dosing above published
      safe levels. Five cases developed despite accepted ophthalmologic patterns of
      screening for toxicity. All cases developed parafoveal retinal pigment epithelial
      atrophic changes and paracentral scotomas to threshold visual field testing.
      CONCLUSIONS: New cases of hydroxychloroquine and chloroquine toxicity continue to
      develop in a screening environment. Increased ophthalmologic attention to dosing,
      awareness of location and nature of early visual field defects, and traditional
      attention to presence or absence of maculopathy can reduce the incidence of this
      avoidable condition.

PMID- 11992863
TI  - Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need
      for treatment with external beam radiotherapy or enucleation.
AB  - PURPOSE: To report the results of chemoreduction and focal therapy for
      retinoblastoma with determination of factors predictive of the need for treatment
      with external beam radiotherapy or enucleation. DESIGN: Interventional case
      series. METHODS: One-hundred three patients with retinoblastoma (158 eyes with
      364 tumors) at the Ocular Oncology Service at Wills Eye Hospital of Thomas
      Jefferson University in conjunction with the Division of Oncology at Children's
      Hospital of Philadelphia from June 1994 to August 1999 were enrolled for this
      prospective clinical trial. The patients received treatment for retinoblastoma
      with six planned cycles (one cycle per month) of chemoreduction using
      vincristine, etoposide, and carboplatin combined with focal treatments
      (cryotherapy, thermotherapy, or plaque radiotherapy). The two main outcome
      measures after chemoreduction and focal therapy were the need for external beam
      radiotherapy and the need for enucleation. The clinical features at the time of
      patient presentation were analyzed for impact on the main outcome measures using
      a series of Cox proportional hazards regressions. RESULTS: Using Reese-Ellsworth
      (RE) staging for retinoblastoma, there were nine (6%) eyes with group I disease,
      26 (16%) eyes with group II disease, 16 (10%) eyes with group III disease, 32
      (20%) eyes with group IV disease, and 75 (48%) eyes with group V retinoblastoma.
      All eyes showed initial favorable response with tumor regression. The median
      follow-up was 28 months (range, 2-63 months). Failure of chemoreduction and need
      for treatment with external beam radiotherapy occurred in 25% of eyes at 1 year,
      27% at 3 years, and no further increase at 5 years. More specifically, external
      beam radiotherapy was necessary at 5 years in 10% of RE groups I-IV eyes and 47%
      of RE group V eyes. Multivariate factors predictive of treatment with external
      beam radiotherapy included non-Caucasian race, male sex, and RE group V disease.
      Failure of chemoreduction and the need for treatment with enucleation occurred in
      13% eyes at 1 year, 29% at 3 years, and 34% at 5 years. More specifically,
      enucleation was necessary in 15% of RE groups I-IV eyes at 5 years and in 53% of
      RE group V at 5 years. Multivariate factors predictive of treatment with
      enucleation included patient age older than 12 months, single tumor in eye, and
      tumor proximity to foveola within 2 mm. Overall, of the 158 eyes, 50% required
      external beam radiotherapy or enucleation and 50% were successfully managed
      without these treatments. No patient developed retinoblastoma metastasis,
      pinealoblastoma, or second malignant neoplasms over the 5-year follow up.
      CONCLUSIONS: Chemoreduction offers satisfactory retinoblastoma control for RE
      groups I-IV eyes, with treatment failure necessitating additional external beam
      radiotherapy in only 10% of eyes and enucleation in 15% of eyes at 5-year follow
      up. Patients with RE group V eyes require external beam radiotherapy in 47% and
      enucleation in 53% at 5 years.

PMID- 11992864
TI  - A double-blind placebo-controlled evaluation of the acute effects of sildenafil
      citrate (Viagra) on visual function in subjects with early-stage age-related
      macular degeneration.
AB  - PURPOSE: To assess the effects of a single 100-mg dose of sildenafil citrate on
      visual function in men with early-stage age-related macular degeneration. DESIGN:
      Randomized double-blind placebo-controlled clinical trial. METHODS: Nine men
      (mean age 71 years, range 59-85 years) with early-stage (minimal visual
      impairment and large drusen in the macula) age-related macular degeneration and
      20/40 or better-corrected visual acuity in at least one eye were prospectively
      randomized to receive either placebo or sildenafil citrate (Viagra; Pfizer Inc,
      New York, New York) 100 mg as a single oral dose. After 7-14 days, they received
      the alternate treatment. Subjects underwent visual acuity, Amsler grid, color
      discrimination (D15), traffic light, Humphrey perimetry, and photo-stress testing
      in each eye before and at specific intervals within 8 hours after dosing.
      RESULTS: Compared with placebo, no pattern of errors were evident in any visual
      function test following sildenafil administration. No statistically or clinically
      relevant changes from baseline were observed in visual acuity, Humphrey perimetry
      (corrected pattern standard deviation), D15 color discrimination, or photo-stress
      tests. No clinically relevant changes were observed in the Amsler grid or traffic
      light tests. Sildenafil treatment was associated with transient mild or moderate
      headache, flushing, and rhinitis. There were no visual adverse events
      spontaneously reported to the investigator. CONCLUSION: A single 100-mg dose of
      sildenafil was well tolerated and produced no acute visual effects or
      exacerbation of preexisting visual impairment in nine men with early-stage age
      related macular degeneration.

PMID- 11992865
TI  - Resolution of papilledema after neurosurgical decompression for primary Chiari I
      malformation.
AB  - PURPOSE: To report a causal relationship between Chiari I malformation and its
      rare, but recognized manifestation of bilateral papilledema. DESIGN:
      Interventional case series. METHODS: Four adult female patients (mean age, 48,
      age range 25-59 years) with bilateral papilledema, signs and symptoms of
      increased intracranial pressure, and cranial magnetic resonance imaging (MRI)
      evidence of a Chiari I malformation ranging from 7 to 22 mm of tonsillar
      herniation underwent suboccipital decompression. RESULTS: In all four patients,
      suboccipital decompression was followed by resolution of bilateral papilledema
      and signs and symptoms of increased intracranial pressure. CONCLUSION: Patients
      with bilateral papilledema and presumed pseudotumor cerebri require a cranial MRI
      to determine if they have a Chiari I malformation, because patients with
      increased intracranial pressure and papilledema from a Chiari I malformation may
      benefit from suboccipital decompression.

PMID- 11992866
TI  - Population prevalence of tilted optic disks and the relationship of this sign to
      refractive error.
AB  - PURPOSE: To assess the prevalence of tilted disks and its association with
      refractive error and visual field defects. DESIGN: Population-based cohort study.
      METHODS: The Blue Mountains Eye Study examined urban Australians aged 49 years or
      older between 1992-1994. Of 4,433 eligible participants, 3,654 (82.4%)
      participated. The eye examination included logMAR visual acuity, standardized
      refraction, cover testing, stereoscopic optic disk photography, and Humphrey
      automated perimetry. Inferior or nasal optic disk tilting was graded from
      stereoscopic photographs. RESULTS: Of 3,583 participants with gradable
      photographs, inferior or nasal optic disk tilting was observed in 77 eyes of 56
      participants (1.6%). The prevalence of tilted disks increased from 0.4% in eyes
      with astigmatism < 1.0 diopters to 17.9% in eyes with astigmatism >or= 5.0
      diopters. The mean astigmatic error was 2.2 diopters in eyes with tilted disks
      compared with 0.7 diopters in eyes with normal disk appearance, P <.001. Myopia
      was present in 66.2% of eyes with tilted disks compared with 12.4% of eyes with a
      normal disk appearance, P <.001. The most common associated features were
      astigmatism (93.5%), pallor, and tessellation of the adjacent chorioretinal
      tissues (74.0%), situs inversus of the retinal vessels (70.1%), beta
      peripapillary atrophy (64.9%), strabismus (30.4%), visual field defects (19.4%),
      posterior staphyloma (18.2%), inferonasal pigmentary accumulation (9.1%), and
      chorioretinal atrophy (5.2%). Superotemporal (33.3%) and superior (25.0%) visual
      field defects were most frequent. CONCLUSIONS: A tilted disk appearance was not a
      rare finding in our study population and was strongly associated with astigmatism
      and higher levels of spherical refractive error, particularly myopia. The tilted
      disk and its associated visual field defect should be distinguished from other
      sinister causes.

PMID- 11992867
TI  - Self-reported visual dysfunction in multiple sclerosis: new data from the VFQ-25
      and development of an MS-specific vision questionnaire.
AB  - PURPOSE: To examine vision-specific health-related quality of life in a cohort of
      patients with multiple sclerosis (MS) using the 25-Item National Eye Institute
      Visual Function Questionnaire (VFQ-25), and to identify content areas for a brief
      MS-specific vision questionnaire. DESIGN: Cross-sectional survey. METHODS: The
      VFQ-25 and a modified version of the Optic Neuritis Treatment Trial (ONTT)
      Patient Questionnaire were administered by in-person interview to 80 patients at
      the University of Pennsylvania MS Center. Binocular visual acuities were obtained
      following a standard protocol using retroilluminated Early Treatment Diabetic
      Retinopathy Study charts. RESULTS: Despite a median binocular visual acuity of
      20/16 (20/12.5-20/250), VFQ-25 subscale scores in the MS cohort were
      significantly lower (worse) compared with those of a published reference group of
      eye disease-free patients (P =.0001-0.009, two-tailed t tests). Rank-correlations
      of VFQ-25 composite (overall) scores with visual acuity were modest, but
      significant (r(s) = 0.33, P =.003), supporting construct validity for VFQ-25
      scores in MS populations. Seven additional aspects of self-reported visual
      dysfunction in MS were also identified. CONCLUSIONS: Patients with MS have a high
      degree of self-reported visual dysfunction that is not entirely captured by
      visual acuity. The VFQ-25 is an effective measure of self-reported visual loss in
      MS. A brief MS-specific vision questionnaire may provide additional useful
      information when administered concurrently with the VFQ-25 in future
      investigations of MS and other neuroophthalmologic disorders.

PMID- 11992868
TI  - Potential new medical therapies for diabetic retinopathy: protein kinase C
      inhibitors.
AB  - PURPOSE: To review the evidence supporting a role for the beta (beta) isoform of
      protein kinase C (PKC) in the pathogenesis of diabetic retinopathy and the
      possible therapeutic benefit of inhibiting this enzyme. DESIGN: Brief literature
      review of research suggesting the potential use for systemic inhibitors of the
      beta isoform of PKC as a medical therapy to prevent the progression of diabetic
      retinopathy. Brief consideration is given to previous, primarily clinical,
      studies dealing with other therapies for this disease. RESULTS: Kinases transfer
      the terminal, "high energy," phosphate group of ATP to a site on a target
      protein, thereby activating the protein, which may be an enzyme, cell membrane
      receptor, or ion transport channel. The PKC family is a group of such enzymes
      that require specific activator molecules, including diacylglycerol, whose
      intracellular concentration is substantially increased during the hyperglycemia
      of diabetes. Protein kinase Cbeta is present at high levels in the retina.
      Increased activation of this enzyme, perhaps by producing tissue hypoxia, leads
      to increased expression of vascular endothelial growth factor, a mitogen that
      increases proliferation of vascular endothelial cells leading to
      neovascularization and enhances breakdown of the blood-retinal barrier, perhaps
      resulting in macular edema. CONCLUSIONS: By interfering with the above
      biochemical pathways, PKC inhibitors may retard or prevent the development and
      progression of diabetic retinopathy. Because members of the PKC family are found
      throughout the body, a generalized inhibitor is likely to be toxic. However, an
      inhibitor specific for PKCbeta may act effectively within the retina and have a
      favorable toxicity profile. Two phase III randomized controlled clinical trials
      of such an inhibitor are now in progress, attempting to evaluate the efficacy of
      this approach to preventing the progression, or inducing regression, of
      "nonclinically significant" diabetic macular edema and of severe nonproliferative
      diabetic retinopathy.

PMID- 11992869
TI  - Corneal endotheliitis and idiopathic sudden sensorineural hearing loss.
AB  - PURPOSE: To report a case with corneal endotheliitis and idiopathic sudden
      sensorineural hearing loss, in which herpes simplex virus type 1 DNA was
      demonstrated in the trabeculum and the aqueous humor by polymerase chain
      reaction. DESIGN: Interventional case report. METHODS: A 60-year-old man
      presented with corneal stromal edema in the right eye and sudden bilateral
      sensorineural hearing loss. The trabeculum excised during trabeculectomy and the
      aqueous humor were examined for the presence of herpes simplex virus type 1 DNA
      by polymerase chain reaction. RESULTS: Polymerase chain reaction demonstrated
      herpes simplex virus type 1 DNA in the aqueous humor and the trabeculum.
      CONCLUSION: Herpes simplex virus type 1 may cause corneal endotheliitis and
      idiopathic sudden sensorineural hearing loss simultaneously.

PMID- 11992870
TI  - Progressive axial myopia in a juvenile patient with traumatic glaucoma.
AB  - PURPOSE: To report a case of progressive axial myopia associated with traumatic
      glaucoma in a juvenile patient with no systemic disease. DESIGN: Interventional
      case report. METHODS: In a 15-year-old male, serial ocular examinations,
      including manifest refraction, tonometry, and axial eye length measurement, were
      performed over a 6-year period, beginning with blunt trauma, right eye, followed
      by a series of surgical procedures for traumatic cataract and glaucoma. RESULTS:
      A 4-diopter myopic shift (from -1.25 to -5.25) with a 1.5 mm increase in the
      axial eye length occurred, whereas the intraocular pressure increased from 21 to
      46 mm Hg, during a 2-year period. The refraction, axial eye length, and
      intraocular pressure remained stable during the same period in the fellow, normal
      eye. CONCLUSION: Progressive axial myopia associated with traumatic glaucoma is
      possible in a juvenile patient in his late teens.

PMID- 11992871
TI  - Isolated Horner syndrome and syrinx of the cervical spinal cord.
AB  - PURPOSE: To alert ophthalmologists to the possibility of a spinal cord lesion in
      individuals with Horner syndrome and no neurologic symptoms. DESIGN:
      Observational case report. METHODS: Neuro-ophthalmic and neuroimaging assessment
      of a 16-year-old man with an isolated Horner syndrome localizing to a first- or
      second-order neuron. RESULTS: With magnetic resonance imaging, a syrinx of the
      cervical spinal cord extending from C5 to C7 was found. No Chiari malformation
      was present. CONCLUSION: Patients with an isolated Horner syndrome localizing to
      a first- or second-order sympathetic neuron should undergo magnetic resonance
      imaging of the head, neck, spinal cord, and chest to investigate for possible
      origins. An isolated Horner syndrome may be the presenting manifestation of a
      cervical syrinx.

PMID- 11992872
TI  - Visual protective sheet can increase blink rate while playing a hand-held video
      game.
AB  - PURPOSE: To evaluate the effectiveness of a protective sheet in reducing eye
      strain caused by unnecessary light reflection on portable liquid crystal display
      panels while playing Game Boy (Nintendo, Kyoto, Japan). DESIGN: Nonrandomized
      clinical trial. METHODS: The blink rates of 24 normal volunteers were measured
      under relaxed conditions while viewing a portable liquid crystal display panel
      and playing Game Boy with and without the protective sheet of polyethylene
      terephthalate with antiglare coating for a total of 10 minutes each. RESULTS: The
      results showed a dramatic increase (from 5.6 +/- 3 to 9.1 +/- 4.9 [P <.0001]) in
      blinks/minute with use of the protective sheet. CONCLUSION: The protective sheet
      has shown the possibility of increasing the blink rate by making the screen
      easier to see.

PMID- 11992873
TI  - An adjustable-tip brush for the induction of posterior hyaloid separation and
      epiretinal membrane peeling.
AB  - PURPOSE: To report a new adjustable-tip brush for induction of posterior hyaloid
      separation and epiretinal membrane peeling. DESIGN: Observational report.
      METHODS: The adjustable-tip brush made of 10-0 nylon was used during vitrectomy
      for a variety of vitreoretinal disorders to induce posterior vitreous detachment
      and to peel internal limiting membrane or epiretinal membranes. RESULTS: The
      instrument was especially effective in inducing posterior vitreous detachment in
      eyes with chronic pseudophakic macular edema and diabetic macular edema. It was
      used successfully to strip thin, immature epiretinal membranes and to unfold
      rolled edges of giant retinal tears. No complications were associated with the
      use of the adjustable-tip brush. CONCLUSION: The adjustable-tip brush was useful
      for posterior hyaloid separation and epiretinal membrane peeling during
      vitrectomy for a variety of vitreoretinal procedures.

PMID- 11992874
TI  - Retinal disorders in preeclampsia studied with optical coherence tomography.
AB  - PURPOSE: To report optical coherence tomography (OCT) of retinal disorders in
      preeclampsia. DESIGN: Observational case report. METHODS: A 24-year-old woman
      developed hypertension (190/100 mm Hg), proteinuria, and generalized edema in the
      34th week of pregnancy. Soon after undergoing a cesarean section, she noted
      severe impairment of vision in both eyes. RESULTS: Ten days after delivery, OCT
      showed a diffuse intraretinal edema that was still present but in a minor degree
      2 months later. Eight months after delivery, macular edema had resolved, but the
      highly reflective band of retinal pigment epithelium (RPE) and choriocapillaris
      was thickened with focal elevations corresponding to the Elschnig spots.
      CONCLUSION: In the acute phase of preeclampsia, OCT revealed a diffuse increase
      in macular thickness. Two months after delivery, macular edema still existed but
      in a minor degree. Eight months after the first examination, OCT depicted
      restoration of the contour of the fovea. Moreover, OCT showed the characteristic
      RPE focal elevations and abnormalities corresponding to the Elschnig spots.

PMID- 11992875
TI  - Atypical choroidal neovascularization in radiation retinopathy.
AB  - PURPOSE: To report atypical choroidal neovascularization associated with
      radiation retinopathy. DESIGN: Case report. METHODS: The patient was examined
      with ophthalmoscopy, fluorescein angiography, and indocyanine green angiography.
      RESULTS: A 32-year-old woman presented with an accelerated course of radiation
      retinopathy with macular edema, capillary telangiectasis, subretinal fluid, and
      lipid during and after pregnancy. Indocyanine green, but not fluorescein
      angiography, demonstrated an unusual area of choroidal neovascularization with
      prominent saccular dilations adjacent to a large zone of poor choroidal
      perfusion. Laser photocoagulation of the choroidal neovascularization resulted in
      an angiographic closure with absorption of the subretinal fluid and improvement
      of visual acuity. CONCLUSIONS: Choroidal neovascularization may be associated
      with radiation retinopathy and, when present, may require indocyanine green
      angiography for its diagnosis.

PMID- 11992876
TI  - Axons in human choroidal melanoma suggest the participation of nerves in the
      control of these tumors.
AB  - PURPOSE: To furnish morphologic evidence of autonomic nervous system influence on
      choroidal melanoma. DESIGN: Histopatholgic case report. METHODS: In the
      enucleated eye of a 72-year-old woman, portions of a mixed-cell choroidal
      melanoma were processed for electron microscopy, and ultrathin sections were
      screened painstakingly under magnifications of x13,000 and x23,000. RESULTS: The
      connective tissue of the melanoma contained macrophages, blood vessels, and
      profiles of several nonmyelinated nerve fiber bundles with a maximum of 6 axons.
      CONCLUSION: The existence of axons in neoplastic tissue indicates nervous input
      and/or output. This led us to conclude that the reaction of the melanoma is
      subjected to vegetative influences, yet to an unknown extent.

PMID- 11992877
TI  - Choroidal metastasis of a gingival squamous cell carcinoma.
AB  - PURPOSE: To report a case of choroidal metastasis of a gingival squamous cell
      carcinoma. DESIGN: Interventional case report. METHODS: Review of the clinical
      history and pathologic findings. RESULTS: A 59-year-old woman with a history of
      right gingival squamous cell carcinoma presented with sudden dimness of vision in
      the left eye of 4 weeks duration. Fundus examination of the left eye revealed a
      yellowish elevated subretinal lesion involving the optic disk and macula. Fine
      needle aspiration biopsy of the choroidal lesion, left eye, revealed metastatic
      squamous carcinoma cells. The patient was referred to a radiation oncologist for
      further management. CONCLUSION: Choroidal metastasis from gingival squamous cell
      carcinoma is rare, and it may develop from hematogeneous spread.

PMID- 11992878
TI  - Spontaneous regression of retinal astrocytic hamartoma in a patient with tuberous
      sclerosis.
AB  - PURPOSE: To report the complete regression of a retinal astrocytic hamartoma in
      conjunction with tuberous sclerosis. DESIGN: Observational case report. METHODS:
      A 12-year-old boy with tuberous sclerosis, diagnosed early in life, was found to
      have a retinal astrocytic hamartoma in his left eye. He had bilateral optic
      atrophy because of long-standing increased intracranial pressure due to a
      cerebral giant cell astrocytoma. He was followed on a yearly basis with fundus
      photography and fluorescein angiography. RESULTS: At the time of initial
      presentation, the minimally elevated intraretinal tumor measured 2 x 1.5 mm. A
      year later, the same tumor measured 1.5 x 1 mm. Two years after initial
      presentation, the tumor totally disappeared. CONCLUSION: This patient has
      demonstrated that retinal astrocytic hamartoma may undergo spontaneous
      regression.

PMID- 11992879
TI  - Retinoblastoma metastatic to the ovary in a patient with Waardenburg syndrome.
AB  - PURPOSE: To report a child with retinoblastoma and Waardenburg syndrome who
      developed ovarian metastases. DESIGN: Interventional case report. METHODS:
      Unilateral retinoblastoma was diagnosed in a 3-year-old girl with Waardenburg
      syndrome and leukocoria in the right eye. The patient had a Reese-Ellsworth Group
      Va tumor and underwent enucleation. Two years later, she developed metastatic
      disease involving the bone marrow, right humerus, both supraorbital bones, and
      both tibias. She was treated with chemotherapy, orbital irradiation, and bone
      marrow transplant but returned 7 months later with back pain and urinary
      retention. RESULTS: Exploratory laparotomy revealed a right ovarian mass, and the
      excised ovary showed metastatic retinoblastoma. The child underwent chemotherapy
      and remained asymptomatic for 9 months, when brain metastases were diagnosed. She
      died within 2 days of admission. CONCLUSION: We believe that this is the first
      description of a patient with retinoblastoma and Waardenburg syndrome and of an
      ovarian metastasis from retinoblastoma.

PMID- 11992880
TI  - Ocular motility in genetically defined autosomal dominant cerebellar ataxia.
AB  - PURPOSE: To describe ocular motility in patients having genetically characterized
      dominant cerebellar ataxia. DESIGN: Observational case series. METHOD: Nine
      ataxic adults having the following molecular genetic diagnoses underwent
      ophthalmic examination and ocular motility recordings: four with spinocerebellar
      ataxia type 6 (SCA-6), three with SCA-3, one with SCA-1, and one with episodic
      ataxia type 2 (EA-2). RESULTS: Versions were normal in eight patients. Most were
      orthotropic, but one with SCA-3 had exotropia at near. The near point of
      convergence was remote in five patients. Eight of nine patients had horizontal
      nystagmus evoked by lateral gaze. All patients with SCA-6 had downbeat nystagmus.
      Downbeat nystagmus was absent in SCA-1, SCA-3, and EA-2. Three patients with SCA
      6 and one with EA-2 had symptomatic improvement when treated with acetazolamide.
      CONCLUSION: Patients with genetically defined dominant cerebellar ataxia
      generally had normal binocular alignment and versions and only mild vergence
      impairment. Downbeat nystagmus was strongly associated with the SCA-6 mutation,
      whose associated episodes of dizziness and imbalance may be relieved by
      acetazolamide.

PMID- 11992881
TI  - Gabapentin attenuates superior oblique myokymia.
AB  - PURPOSE: To investigate therapeutic effects of oral gabapentin therapy on
      superior oblique myokymia. DESIGN: Observational case series with measurement of
      visual acuity and eye movements before, during, and after therapy. METHODS: Two
      adult patients with superior oblique myokymia, refractory to other therapies,
      were treated with gabapentin orally after informed consent was obtained. Eye
      movements were measured using the magnetic search coil technique. RESULTS:
      Superior oblique myokymia completely resolved after starting gabapentin.
      CONCLUSION: Gabapentin may be an effective treatment for superior oblique
      myokymia; a double-blind study seems justified.

PMID- 11992882
TI  - Resolution of acute acquired comitant esotropia after suboccipital decompression
      for Chiari I malformation.
AB  - PURPOSE: To report a case of acute comitant esotropia successfully treated with
      suboccipital decompression in a 9-year-old male patient with Chiari I
      malformation. DESIGN: Interventional case report. METHODS: A 9-year-old male with
      Chiari I malformation had acute onset of diplopia, headache, and comitant
      esotropia. RESULTS: About 9 months after suboccipital decompression, diplopia
      resolved and there was near orthophoria on examination 15 months after surgery.
      CONCLUSION: In view of our case and after a review of literature, we advocate
      primary suboccipital decompression to treat acute comitant esotropia in patients
      with Chiari I malformation. A follow-up period of at least 1 year rather than 6
      months seems necessary to assess surgery effects.

PMID- 11992883
TI  - Sneeze-induced visual and ocular motor dysfunction.
AB  - PURPOSE: The purpose of this report is to describe two neuroophthalmic
      complications that are related by their temporal association with a sneeze.
      DESIGN: We describe observational case reports of two patients. METHODS: Both
      patients were examined, and their conditions were diagnosed and treated according
      to standard indications for each neuroophthalmic condition. RESULTS: The first
      case describes a patient who had previously undergone intracranial surgery,
      including removal of the clivus and later developed a trochlear nerve paresis
      after a sneeze. The second case describes a patient who repeatedly demonstrates
      transient decreased perfusion to his right central retinal artery and an
      associated afferent papillary defect after sneezing. CONCLUSION: The mechanical
      and hemodynamic forces involved in sneezing are formidable and may cause
      permanent cranial neuropathy or temporarily alter ocular blood flow in certain
      patients.

PMID- 11992884
TI  - Late recurrence of unilateral graves orbitopathy on the contralateral side.
AB  - PURPOSE: To report a case of late recurrence of unilateral Graves orbitopathy on
      the contralateral side after 7 years. DESIGN: Interventional case report.
      METHODS: A 44-year-old woman with left unilateral Graves orbitopathy underwent
      two-wall orbital decompression on the left side. After strabismus surgery and
      left upper eyelid surgery, she was discharged. RESULTS: Seven years after
      discharge, the patient developed Graves orbitopathy on the right side, and she
      underwent two-wall orbital decompression on the right side. CONCLUSION: At least
      in patients with unilateral Graves orbitopathy, late recurrence of the disease in
      the contralateral orbit may occur.

PMID- 11992885
TI  - Gorham disease of the orbit.
AB  - PURPOSE: To report a case of Gorham disease, also known as vanishing bone
      disease, of the orbit. DESIGN: Interventional case report. METHODS: A 43-year-old
      Caucasian woman developed a depression in her left temple, pulsation in her left
      upper eyelid and temple, and bulging of the left upper eyelid and headache.
      Computerized tomography revealed a lytic lesion in the roof of the left orbit.
      RESULTS: Intraoperative examination of the lesion revealed a bony defect in the
      left orbital roof. Surgical intervention resulted in improvement of her symptoms,
      and pathology failed to reveal evidence of malignancy or other benign neoplastic
      process. CONCLUSION: Gorham disease should be considered in the differential
      diagnosis of lytic bony lesions of the orbit.

PMID- 11992886
TI  - Foveal translocation with scleral imbrication in patients with myopic neovascular
      maculopathy.

PMID- 11992888
TI  - Travoprost compared with latanoprost and timolol in patients with open-angle
      glaucoma or ocular hypertension.

PMID- 11992891
TI  - Skew deviation and inferior oblique palsy.

PMID- 11992905
TI  - Residual mercury content and leaching of mercury and silver from used amalgam
      capsules.
AB  - OBJECTIVE: The objective of this investigation was to carry out residual mercury
      (Hg) determinations and toxicity characteristic leaching procedure (TCLP)
      analysis of used amalgam capsules. METHODS: For residual Hg analysis, 25 capsules
      (20 capsules for one brand) from each of 10 different brands of amalgam were
      analyzed. Total residual Hg levels per capsule were determined using United
      States Environmental Protection Agency (USEPA) Method 7471. For TCLP analysis, 25
      amalgam capsules for each of 10 brands were extracted using a modification of
      USEPA Method 1311. Hg analysis of the TCLP extracts was done with USEPA Method
      7470A. Analysis of silver (Ag) concentrations in the TCLP extract was done with
      USEPA Method 6010B. RESULTS: Analysis of the residual Hg data resulted in the
      segregation of brands into three groups: Dispersalloy capsules, Group A, retained
      the most Hg (1.225 mg/capsule). These capsules were the only ones to include a
      pestle. Group B capsules, Valliant PhD, Optaloy II, Megalloy and Valliant Snap
      Set, retained the next highest amount of Hg (0.534-0.770 mg/capsule), and were
      characterized by a groove in the inside of the capsule. Group C, Tytin regular
      set double-spill, Tytin FC, Contour, Sybraloy regular set, and Tytin regular set
      single-spill retained the least amount of Hg (0.125-0.266 mg/capsule). TCLP
      analysis of the triturated capsules showed Sybraloy and Contour leached Hg at
      greater than the 0.2 mg/l Resource Conservation and Recovery Act (RCRA) limit.
      SIGNIFICANCE: This study demonstrated that residual mercury may be related to
      capsule design features and that TCLP extracts from these capsules could, in some
      brands, exceed RCRA Hg limits, making their disposal problematic. At current RCRA
      limits, the leaching of Ag is not a problem.

PMID- 11992906
TI  - Effect of adhesive layer properties on stress distribution in composite
      restorations--a 3D finite element analysis.
AB  - OBJECTIVES: Teeth, adhesively restored with resin-based materials, were modeled
      by 3D-finite elements analysis that showed a premature failure during
      polymerization shrinkage and occlusal loading. METHODS: Simulation of Class II
      MOD composite restorations with a resin bonding system revealed a complex
      biomechanical behavior arising from the simultaneous effects of polymerization
      shrinkage, composite stiffness and adhesive interface strain. Due to a
      polymerization contraction, shrinkage stress increases with the rigidity of the
      composites utilised in the restoration, while the cusp movements under occlusal
      loading are inversely proportional to the rigidity of the composites. The
      adhesive layer's strain also plays a relevant role in the attenuation of the
      polymerization and occlusal loading stresses. RESULTS: The choice of an
      appropriately compliant adhesive layer, able to partially absorb the composite
      deformation, limits the intensity of the stress transmitted to the remaining
      natural tooth tissues. For adhesives and composites of different rigidities, FEM
      analysis allows the determination of the optimal adhesive layer thickness leading
      to maximum stress release while preserving the interface integrity. Application
      of a thin layer of a more flexible adhesive (lower elastic modulus) leads to the
      same stress relief as thick layers of less flexible adhesive (higher elastic
      modulus).

PMID- 11992907
TI  - Effect of resins sealing of dentin on the bond strength of ceramic restorations.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate shear bond
      strengths when ceramic cylinders were bonded to dentin following the use of
      different dentin adhesive systems as desensitizers. METHODS: Freshly extracted
      human molars were selected. Their buccal dentin was exposed and a standardized
      circular area was isolated. Dentin desensitizers included an experimental self
      curing 'one-bottle' adhesive system, two light-curing 'one-bottle' bonding
      systems and a conventional three component adhesive system, which was selected as
      a control system. Ten teeth were prepared for each test group (40 teeth total). A
      layer of an eugenol-free temporary cement was applied on the treated surface and
      the specimens were stored in distilled water for 1 week. After the removal of
      cement, the dentin surfaces were cleaned, re-etched and a layer of the
      experimental self-curing 'one-bottle' adhesive was applied. Standardized
      cylindrical ceramic samples were luted using a resin cement. One week later,
      shear bond strengths were determined using a universal testing machine. The bond
      strength values obtained were tested for a statistical significance with Kruskall
      Wallis one-way analysis of variance. The type of failure occurring on each
      specimen was observed and recorded by means of an optical and a scanning electron
      microscope. RESULTS: Mean shear bond strengths of the four groups ranged from
      25.84 to 27.83 MPa and they were not significantly different. Most failures were
      cohesive in dentin. SIGNIFICANCE: The use of an adhesive system as a dentin
      desensitizing agent before cementation does not alter the retentive strength of
      adhesively luted ceramic restorations.

PMID- 11992908
TI  - Cytotoxicity of orthodontic bands, brackets and archwires in vitro.
AB  - OBJECTIVES: In orthodontic therapy, different materials are used and subjected to
      a damp oral environment, which can modify their properties. In order to evaluate
      the biocompatibility of metallic and non-metallic orthodontic appliances their in
      vitro cytotoxicity has been measured. METHODS: Twenty-eight new and nine
      clinically used materials, including brackets, molar bands and archwires were
      used. The metallic materials were made of stainless steel, gold-plated steel,
      pure titanium, nickel-titanium, titanium-molybdenum and silver-based soldering
      alloy. The non-metallic materials were in polycarbonates and ceramics. After a
      release period of the material in the culture medium (0.1 mg/ml) for 3 and 14
      days, the viability of fibroblasts L929 cultivated with this medium was compared
      to negative control with MTT assay. RESULTS: The results showed the non
      cytotoxicity of the materials. The metallic and non-metallic materials were
      similar in terms of cytotoxicity. The cytotoxicity of clinically used samples was
      equivalent to that of the same non-used samples, except a cytotoxic sample, at 14
      days, corresponding to a soldered and clinically used molar band. The 3 day
      results were different from the 14 day results in six cases out of 37.
      SIGNIFICANCE: In spite of the presence of one cytotoxic sample, the orthodontic
      materials can be considered as non cytotoxic. However, the practitioner should
      pay attention to the composition and the polish of soldering silver-based alloys
      containing copper and zinc in order to limit cytotoxic ion release. The
      cytotoxicity of the used sample related to ion release might be related to some
      clinical sub-acute effects related with orthodontic materials, thus a long term
      release period may be suitable to evaluate in vitro the sub-acute clinical
      effects of alloys.

PMID- 11992909
TI  - Responses of L929 mouse fibroblasts, primary and immortalized bovine dental
      papilla-derived cell lines to dental resin components.
AB  - OBJECTIVE: The use of adequate target cells for cytotoxicity testing of dental
      restorative materials has often been experimentally assessed with respect to the
      clinical relevance of the test results. In the present study, the responses in
      primary bovine dental papilla-derived cells (pulp cells) were compared with those
      in transformed dental papilla-derived cell lines and L929 mouse fibroblasts after
      exposure to various dental resin compounds. METHODS: Primary bovine dental
      papilla-derived cells (CPC), tCPC B (CPC cells transformed with SV40 T-antigen),
      tCPC E (CPC cells transformed with E6/E7 oncogen), and L929 mouse fibroblast
      cells were exposed to various compounds of dental resin materials for 24 h, and
      cytotoxicity was determined using the MTT assay. Bis-GMA, UDMA, 1,6 hexane diol
      dimethacrylate (HDDM), TEGDMA, HEMA, MMA, camphorquinone (CQ), bisphenol A (BPA),
      and glycidyl methacrylate (GMA) were tested. Concentrations leading to 50% cell
      survival (TC50 values) were calculated from fitted dose-response curves. RESULTS:
      The simple ranking of the cytotoxic effects of the dental resin compounds in the
      four cell types was identical, and TC50 values determined in L929 cells here were
      consistent with findings by other authors using continuous cell lines. However,
      the concentrations of the resin compounds necessary for eliciting cytotoxic
      responses in the various cells were clearly different. The analyses of TC50
      values of the resin compounds revealed a linear correlation between cell lines,
      and the overall sensitivities increased as follows: CPC=tCPC B<tCPC E<L929.
      SIGNIFICANCE: The low sensitivities of primary cells and transformed tCPC B cells
      compared with the continuous L929 cell line and the transformed tCPC E cells
      indicates the presence of specific structural and functional properties relevant
      in vivo. The differences between the transformed tCPC B and tCPC E cells may
      indicate modifications of cellular functions caused by the different
      transformation processes.

PMID- 11992910
TI  - Laser interferometric method for measuring linear polymerization shrinkage in
      light cured dental restoratives.
AB  - OBJECTIVE: A novel laser interferometric method for monitoring linear
      polymerization shrinkage in dental restoratives is demonstrated. METHODS: The
      experimental apparatus consists of a low power Helium-Neon laser, a home-built
      Michelson interferometer, amplified photodiode detectors, and a computer data
      acquisition system. The feasibility of using interferometry to measure linear
      shrinkage was evaluated by measuring the percent linear contraction in five
      commercially available light cured restorative systems. RESULTS: Five-min
      interferometric curing profiles were collected for each restorative using a 400
      mW/cm2 curing light irradiance. The 'interferograms' were converted into percent
      linear contraction profiles that revealed the relative kinetics of material
      shrinkage. The overall percent linear contraction after 5 min compares favorably
      with literature data for the five commercial restoratives studied here.
      SIGNIFICANCE: Interferometry offers several advantages over conventional methods
      of measuring polymerization contraction. These advantages include the inherent
      sensitivity and accuracy offered by interferometric measurements; the instrument
      does not need to be calibrated since the wavelength of the laser light source
      provides an accurate length standard. Also, the ability to collect data at high
      acquisition rates allows for the real-time characterization of unusually fast
      photopolymerization reactions. The low cost and relative ease of use associated
      with the apparatus are also advantageous.

PMID- 11992911
TI  - Effect of small additions of Ir on properties of a binary Au-Ti alloy.
AB  - OBJECTIVES: Previous investigations in the binary system Au-Ti have shown that a
      Au based alloy with 1.7 wt% Ti reveals properties, which are appropriate to
      dental applications. Aim of this investigation was to refine the coarse grained
      dendritic microstructure of the alloy. Derived from experience with traditional
      high gold alloys and based on theoretical considerations, Ir was chosen as
      potential grain refiner and its influence on grain size, hardness, and thermal
      distortion was investigated. METHOD: Seven different Au-Ti alloys with Ir
      contents of 0-0.5 wt% were prepared in an arc furnace and test pieces cast by the
      dental casting technique. Microstructures of the alloys were documented by light
      microscopy. Grain size was assessed by a comparison procedure, hardness was
      measured by the indentation test, and thermal distortion by a three point bending
      test in a modified dilatometer. RESULTS: It revealed that Ir has a grain refining
      effect on the alloy with smallest grain sizes at a concentration of at least 0.3
      wt%. It seems that the alloy with 0.5 wt% Ir shows slight grain growth during
      firing. Little homogenization was observed after firing. The influence of Ir on
      hardness was negligible. Thermal distortion is minimized with a concentration of
      0.1 wt% Ir. In order to profit by the high thermal distortion resistance, the
      alloy Au(98.2)Ti(1.7)Ir(0.1) (wt) was chosen as definite composition, although
      0.1 wt% Ir does not satisfactorily refine the alloy. SIGNIFICANCE: The alloy
      Au(98.2)Ti(1.7)Ir(0.1) (wt) revealed properties appropriate for the crown and
      bridge technique.

PMID- 11992912
TI  - Influence of residual surface investment material on crystallization shrinkage of
      a mica-based glass-ceramic.
AB  - OBJECTIVE: It has been reported that residual surface investment material induced
      precipitation of a second phase in the surface of a mica-based castable glass
      ceramic. The objective of this study was to investigate the influence of this
      precipitate on the crystallization shrinkage of the glass-ceramic. METHODS: In
      experiment 1, six glass bars were cast. The whole surface of three of the six
      bars was ground to remove residual surface investment material. Then, the six
      bars were treated thermally to induce crystallization. Dimensional change in the
      bars during the treatment was recorded. In experiment 2, 14 glass specimens were
      assigned to two groups. Seven specimens in the one group would form the second
      phase. The length of each specimen was measured pre- and post-crystallization,
      and the crystallization shrinkage value calculated. RESULTS: In experiment 1, all
      specimens showed shrinkage during thermal processing. The majority of
      crystallization shrinkage began around 620 degrees C and finished at 750 degrees
      C. Specimens with the residual investment showed less net shrinkage than those
      without the investment. In experiment 2, mean shrinkage values and standard
      deviations were 1.11 (0.05)% for the group without the investment and 0.93
      (0.11)% for the group with the investment. There was a significant difference
      between the groups (P<0.01). SIGNIFICANCE: The residual surface investment
      material decreases the crystallization shrinkage, and must affect the strength of
      the mica-based glass-ceramic and the fit of this ceramic restorative to the
      prepared cavity.

PMID- 11992913
TI  - Resistance of an enamel-bonding agent to saliva and acid exposure in vitro
      assessed by liquid scintillation.
AB  - OBJECTIVES: To determine the leakage and resistance of a bonding agent and a
      light-curing fine hybrid composite when exposed to saliva or lactic acid (pH 4)
      in vitro. METHODS: Twenty discs in each of four groups of selected irradiated
      bovine lower central incisors were treated with one of three sealing options: an
      enamel bond (Heliobond, Vivadent, Schaan, Liechenstein) in a single-step
      application; Heliobond in a two-step application; and Tetric Flow (Vivadent) as
      the negative control. One group served as the positive control and remained
      unsealed. Loss of apatite was determined using the radiochemical method of liquid
      scintillation. The Cherenkov radiation was assessed in order to evaluate the acid
      resistance and leakage of smooth surface enamel bonding after exposure to saliva
      and lactic acid. In addition, replicas were made for SEM analysis of
      micromorphologic surface changes. RESULTS: A mean loss of 416.5 g (s.d. 57.0)
      apatite was observed over the unsealed sites following 14 days of exposure to
      lactic acid. The application of Heliobond in a one- and two-step application
      still revealed a remarkable degree of leakage, and substance losses of 196.5 g
      (s.d. 38.9) and 161.8 g (s.d. 39.7), but a protective potential was evident. In
      saliva, untreated, as well as sealed teeth, showed a modest leakage that was less
      than 20 g. When Tetric Flow was used (negative control) leakage was reduced to a
      minimum of 2.4 g (s.d. 1.0) in saliva and 12.8 g (s.d. 19.6) in lactic acid.
      These results were confirmed by SEM analysis. SIGNIFICANCE: The method of liquid
      scintillation was revealed to be of considerable value in evaluating leakage and
      acid resistance of potential smooth enamel sealing options. Sealing with an
      unfilled resin still demonstrated remarkable levels of acid dissolution, although
      a protection tendency could be observed. This leads to the conclusion that there
      is a need for further investigation to establish more acid-resistant enamel
      sealing agents.

PMID- 11992914
TI  - Marginal integrity of different resin-based composites for posterior teeth: an in
      vitro dye-penetration study on eight resin-composite and compomer-/adhesive
      combinations with a particular look at the additional use of flow-composites.
AB  - OBJECTIVE: To determine improvements in marginal adaptation of resin-based
      composite restorative systems by means of flow-composites (Solitaire 2/Gluma
      Solid Bond, Solitaire 2/Flow Line/Gluma Solid Bond, Point 4/Optibond Solo Plus,
      Point 4/Revolution/Optibond Solo Plus) and to determine the equality of
      simplified bonding systems (Solitaire 2/Gluma Comfort Bond, Tetric Ceram/Tetric
      Flow/Excite, Dyract AP/Prime & Bond NT/NRC, Pertac II/Prompt-L-Pop) in marginal
      gap formation. METHODS: The marginal dye penetration (2% methylene-blue) was
      investigated separately for the approximal boxes of Class II mod-cavities with
      one cervical margin of the approximal box within enamel, the other within
      cementum. The surface analysis determined the percentage of dye-penetrated
      cervical and lateral margins of the approximal boxes, while the in depth
      investigation reported the mean dye penetration (mm) at both different cervical
      margins. RESULTS: After thermocycling (5000 x , 5-55 degrees C) the percentage of
      dye penetration at the cervical cementum margins ranged from 16.5 +/- 5.9%
      (Solitaire/Flow Line/Gluma Solid Bond) to 82.8 +/- 5.7% (Pertac II/Prompt L-Pop),
      for the cervical enamel margins from 10.1 +/- 5.2% (Dyract AP/NRC/P & B NT) to
      72.7 +/- 7.9% (Pertac II/Prompt L-Pop), and for the lateral enamel margins of the
      approximal boxes from 4.8 +/- 2.3% (Dyract AP/NRC/P & B NT) to 53.9 +/- 6.8%
      (Pertac II/Prompt L-Pop). In the in-depth dye penetration investigation the mean
      dye penetration ranged from 0.2 +/- 0.2 mm (Point 4/Revolution/Optibond Solo
      Plus) to 1.7 +/- 0.2 mm (Pertac II/Prompt L-Pop) at the cementum margins. At the
      enamel margins only Pertac II/Prompt L-Pop and Solitaire 2/Gluma Solid Bond
      showed mean in depth dye-penetrations deeper than 0.1 mm. SIGNIFICANCE: Pertac
      II/Prompt-L-Pop showed a statistically significant (significance level alpha =
      0.05, Wilcoxon test) higher percentage of dye-penetrated margins than most of the
      other restorative systems.

PMID- 11992915
TI  - Use of porcine small intestinal submucosal graft in the surgical management of
      tunical deficiencies with penile prosthetic surgery.
AB  - OBJECTIVES: To report the use of a new acellular xenographic porcine jejunal
      submucosal graft as a closure material for tunica albuginea deficiencies (distal
      erosion, attenuation) after penile prosthesis insertion. METHODS: Seventeen
      patients with at least a 36-month history of having an indwelling three-piece
      inflatable penile prosthesis developed tunica albuginea deficiencies. Nine
      patients with unilateral distal erosion of the tunica and eight with attenuation
      of the tunica underwent penile prosthesis revisionary surgery and tunical
      reconstruction using lyophilized small intestinal submucosa (Surgisis). The
      reconstructive techniques used a suprapubic and subcoronal incisional approach
      and a new three-piece inflatable prosthesis. RESULTS: Reconstructive surgical
      correction of the tunical defect was achieved in all 17 patients. At a mean
      follow-up of 21 months (range 6 to 34), no patient had had separation of the
      graft from the tunica or recurrence of the deficiency. All patients had a
      satisfactorily functioning prosthesis. Infection, pain, bulging, or evidence of a
      local inflammatory response at the graft site has not occurred. No patient
      required any additional surgery. CONCLUSIONS: At the initial long-term follow-up,
      acellular porcine jejunal submucosal grafts for coverage of tunical deficiencies
      with penile prosthetic surgery allow for satisfactory clinical results. The ease
      of surgical handling and placement, elimination of nonabsorbable synthetic
      grafting materials, and no associated comorbidities from graft harvesting
      techniques, coupled with no adverse reactions, make this graft an anatomic and
      functional tunical substitute.

PMID- 11992916
TI  - Pediatric renal trauma.
AB  - OBJECTIVES: To review the pediatric renal trauma cases during the past 10 years
      to determine the appropriate indications for imaging and operative intervention.
      METHODS: We searched the medical records from 1989 to 1999 and identified 61
      patients aged up to 18 years old with objective data on renal trauma grade by
      either computed tomography or operative exploration and analyzed the data.
      RESULTS: Of the 61 cases, 46 were blunt and 15 were penetrating injuries. Thirty
      two (70%) of 46 patients with blunt injuries and all 15 patients (100%) with
      penetrating injuries sustained significant grade 2-5 injuries. The 14 grade 1
      blunt injuries included 4 (29%) with gross hematuria, 7 (50%) with microscopic
      hematuria, and 3 (21%) with normal urinalyses. The 32 grade 2-5 blunt injuries
      included 20 (63%) with gross hematuria, 8 (25%) with microscopic hematuria, and 4
      (13%) with normal urinalyses. The 15 grade 2-5 penetrating injuries included 9
      (60%) with gross hematuria, 2 (13%) with microscopic hematuria, and 4 (27%) with
      normal urinalyses. Five of the blunt (11%) and 13 of the penetrating (87%)
      injuries were managed with renal operative intervention, including 12 repairs of
      lacerations or vessel injuries and 6 nephrectomies. CONCLUSIONS: Renal injuries
      of significant grade were encountered that presented with microscopic hematuria,
      as well as with normal urinalysis findings. Therefore, the decision for renal
      imaging for the diagnosis and grading of renal injuries should not be based on
      urinalysis alone in isolation from clinical status, history, and mechanism of
      injury. Although the vast majority of renal injuries do not require surgical
      intervention, their accurate grading prompts treatment with surveillance, bed
      rest, and close in-hospital monitoring.

PMID- 11992919
TI  - Simple technique to stabilize the costochondral junction using synthetic mesh
      after a thoracoabdominal incision.
AB  - We describe a technique to assist in the stabilization of the costochondral
      junction using a small strut of synthetic mesh in patients undergoing a
      thoracoabdominal incision.

PMID- 11992920
TI  - Ethanol injection therapy for locally invasive prostatic adenocarcinoma.

PMID- 11992921
TI  - Occult renal cell carcinoma in a patient with polymyositis.
AB  - Polymyositis (PM) is associated with an increased risk of malignancy. We report a
      case in which a 45-year-old patient with PM underwent computed tomography to
      search for an occult malignant process. The evaluation revealed a left renal mass
      that was treated successfully by laparoscopic radical nephrectomy. Pathologic
      evaluation revealed a clear cell renal cell carcinoma. The patient remained free
      of disease at 2 years postoperatively and required decreasing amounts of
      medication to manage his PM. This suggests that renal malignancies may contribute
      to the PM disease process in a paraneoplastic fashion and that screening for
      occult malignancy in the presence of PM is warranted.

PMID- 11992922
TI  - Management of urethral straddle injury after radical prostatectomy.
AB  - Incontinence, impotence, and urethral stricture are reported complications of
      radical retropubic prostatectomy. Although complications are possible after
      urethroplasty for anterior urethral trauma as well, the combined risk in patients
      requiring this operation after radical retropubic prostatectomy is unknown. The
      first reported case involving the management of urethral trauma after radical
      prostatectomy is presented.

PMID- 11992923
TI  - Mixed tumor of paratesticular rhabdomyosarcoma and an adenomatoid tumor in an
      elderly patient.
AB  - We report a case of a mixed tumor of paratesticular rhabdomyosarcoma and an
      adenomatoid tumor in an elderly patient. Rhabdomyosarcoma is one of the most
      common childhood tumors; however, it rarely occurs in the elderly. In addition,
      to our knowledge, paratesticular rhabdomyosarcoma and adenomatoid tumor rarely
      form mixed tumors. Finally, we consider the pathogenesis of diploblastic tumors.

PMID- 11992924
TI  - Antegrade periurethral administration of Durasphere for management of a
      vesicoperineal fistula.
AB  - A patient who had developed a persistent fistula between the urethra and bladder
      neck after its surgical closure in the construction of a continent urinary pouch
      and Mitrofanoff nipple was successfully treated by antegrade periurethral
      injection of a newly approved injectable bulking agent for stress urinary
      incontinence (Durasphere) to occlude the bladder neck. We believe this to be the
      first reported use of Durasphere for such treatment.

PMID- 11992925
TI  - Squamous cell carcinoma in a female urethral diverticulum.
AB  - A 38-year-old woman was found to have a squamous cell carcinoma in a urethral
      diverticulum after a simple diverticulectomy. The aggressiveness of this
      histologic subtype of carcinoma, along with this patient's long life expectancy,
      supported the choice of aggressive therapy. Only nine other cases have been
      reported. A brief review of the published reports on the presentation, diagnosis,
      options for treatment, and outcomes is included.

PMID- 11992926
TI  - Chylous ascites from prostatic adenocarcinoma.
AB  - Chylous ascites secondary to malignancy is usually associated with
      lymphoproliferative disorders such as Hodgkin's and non-Hodgkin's lymphoma. Other
      neoplasms include carcinoma of the pancreas, stomach, breast, ovary, carcinoid,
      kidney, and prostate. Chylous ascites secondary to carcinoma of the prostate is,
      however, extremely rare. The prognosis in these patients is usually poor and most
      patients die within a few months after diagnosis.

PMID- 11992927
TI  - Positive expression of HIF-2alpha/EPAS1 in invasive bladder cancer.
AB  - OBJECTIVES: To investigate the expression of hypoxia-inducible factor (HIF)
      2alpha/endothelial PAS domain protein 1 (EPAS1) in bladder cancer. METHODS: Two
      bladder cancer cell lines (T24, EJ-1) were examined for the expression of HIF
      2alpha/EPAS1 mRNA by reverse transcriptase-polymerase chain reaction and HIF
      2alpha/EPAS1 protein by Western blot analysis, respectively. Expression of HIF
      2alpha/EPAS1 protein was also investigated immunohistochemically on paraffin
      embedded sections from 24 patients with bladder cancer. RESULTS: HIF-2alpha/EPAS1
      mRNA and protein could be detected in the two bladder cell lines under normoxia.
      The normal urothelium and all 7 superficial cases (pTis-pTa) were negative for
      HIF-2alpha/EPAS1. Five of the 8 pT1 cases (62.5%) and all 9 muscle-invasive cases
      were positive. The invasive compartment showed stronger HIF-2alpha/EPAS1
      immunoreactivity compared with the superficial compartment. All the tumor
      clusters infiltrating to the interstitial tissue among muscle fibers showed
      moderate to strong positive staining. CONCLUSIONS: HIF-2alpha/EPAS1 is mostly
      expressed in invasive bladder cancer, which indicates a possible role for HIF
      2alpha/EPAS1 in the invasion of bladder cancer.

PMID- 11992928
TI  - The decision to undergo DNA or protein synthesis is determined by the degree of
      mechanical deformation in human bladder muscle cells.
AB  - OBJECTIVES: To investigate the effect of varying levels of mechanical deformation
      (cyclic stretch-relaxation) on protein and DNA synthesis rates in human bladder
      smooth muscle cells (SMCs). Cells in the bladder wall respond to outlet
      obstruction by increasing rates of protein synthesis ("hypertrophy") and/or DNA
      synthesis ("hyperplasia"); however, it is not established how these distinct
      processes are initiated. METHODS: Primary cultures of human bladder SMCs were
      generated and maintained according to published methods. Cells were plated on
      type I collagen-coated elastomer-bottomed plates and subjected to cyclical
      stretch-relaxation (0.1 Hz) at 6%, 12%, and 20% elongation using a computer
      controlled stretch-inducing device. DNA and protein synthesis rates were
      determined by uptake of radiolabeled thymidine and leucine, respectively.
      Nonstretched cells served as controls. RESULTS: Mechanical stretch stimulated DNA
      synthesis in a dose and time-dependent manner with marked upregulation (4.5-fold)
      in response to 20% elongation. Mechanical deformation also elicited changes in
      protein synthesis in bladder SMCs. However, in contrast to the DNA synthesis
      pattern, leucine uptake over time was stimulated at 6% and 12% elongation, and no
      protein synthesis response was seen at 20% elongation. CONCLUSIONS: Our findings
      suggest that stretch, in isolation from other potential mediators such as
      pressure or hypoxia, can induce either a hyperplastic or hypertrophic response in
      bladder SMCs and that the cells' response is dependent on the intensity of the
      stretch stimulus. These observations may be relevant to the process of in vivo
      tissue remodeling stimulated by bladder distension or contractile dysfunction.

PMID- 11992929
TI  - Detection of low-molecular-mass plasma peptides in the cavernous and systemic
      blood of healthy men during penile flaccidity and rigidity--an experimental
      approach using the novel differential peptide display technology.
AB  - OBJECTIVES: To use Differential Peptide Display (DPD) technology to evaluate the
      patterns of low-molecular-mass peptides and small proteins in the systemic and
      cavernous blood taken from healthy adult male volunteers during the penile stages
      of flaccidity and rigidity. Results from basic research implicate a role of
      various peptides in the control of mammalian penile erectile tissue.
      Nevertheless, it is not yet known which particular peptides are essential in the
      regulation of penile flaccidity, tumescence, rigidity, and detumescence. METHODS:
      Five healthy male subjects were exposed to visual and tactile erotic stimuli to
      elicit penile erection. Whole blood was simultaneously aspirated from the corpus
      cavernosum and cubital vein during penile flaccidity and rigidity. Plasma
      aliquots were subjected to DPD analysis by means of matrix-assisted-laser
      desorption-ionization mass mapping and electrospray-ionization quadrupole--time
      of-flight mass spectrometry. RESULTS: High-resolution two-dimensional peptide
      mass mapping revealed differences in the systemic and cavernous plasma samples
      related to penile flaccidity and rigidity. Distinct signals were recognized in
      the cavernous but not in the systemic plasma obtained during flaccidity. These
      signals were not registered in the plasma samples obtained from the corpus
      cavernosum during rigid erection. Although one signal was identified as the blood
      coagulation-activating peptide XIIIa, the remaining two signals could not be
      related to any known peptide. These signals may represent unknown local
      peptidergic factors that might be involved in the regulation of penile
      flaccidity. CONCLUSIONS: Our study demonstrates that DPD is a feasible method for
      detecting differences in the cavernous and systemic blood in relation to the
      different functional conditions of the penile erectile tissue. Additional studies
      using DPD should include the analysis of blood samples taken from the cavernous
      meshwork of healthy subjects during penile tumescence and detumescence to
      establish DPD as a valuable tool in contemporary corpus cavernosum basic
      research.

PMID- 11992930
TI  - GOMCO circumcision clamp; an enduring and unexpected success.

PMID- 11992933
TI  - Processing and use of human freeze-dried bone allografts in implant dentistry.

PMID- 11992934
TI  - The impulse factor in cosmetic case acceptance.

PMID- 11992935
TI  - Trigeminal neuralgia in dentistry.

PMID- 11992936
TI  - Regenerating the ridge: performance of the Grafton allograft.

PMID- 11992937
TI  - The use of platelet-rich plasma to enhance the success of bone grafts around
      dental implants.

PMID- 11992938
TI  - For 2000 and beyond: Trends that will shape oral health.

PMID- 11992939
TI  - Allied success: making the most of the relationship between the doctor and the
      lab technician.

PMID- 11992940
TI  - Traditional pain management methods gain popularity.

PMID- 11992941
TI  - Screening and medical evaluation of adults: contraindications for invasive dental
      procedures.
AB  - Implant and preprosthetic surgeries aim to restore normal anatomical contours,
      function, comfort, esthetics, and oral health. Systemic screening of a patient
      prior to implant and/or biomaterial insertion is critical to patient well being
      and success of the surgical procedure(s). It is no longer appropriate to limit
      the general contraindications to the malfunction of major organs and systems and
      not consider the devastating long-term effects of an unhealthy lifestyle
      (smoking, inadequate diet, etc.). Modern standards of care should not
      systematically exclude patients with relative or marginal health conditions
      without exploring the possibilities of improving and stabilizing those
      conditions. Based on the classification of the American Society of
      Anesthesiology, a number of absolute and relative contraindications are
      presented. Treatments are proposed for optimizing some marginal health conditions
      and stabilizing unbalanced physiological function prior to surgery. A knowledge
      of the fundamentals of internal medicine is an important prerequisite for
      predictable implant and preprosthetic surgery. This paper reflects the opinion of
      a physician and dentist who has been actively involved in implant and
      preprosthetic surgery for the past quarter of a century in both private and
      university hospital practice.

PMID- 11992942
TI  - Management of anterior spacing with orthodontics and prosthodontics.
AB  - Closing maxillary and mandibular diastemas is facilitated by a multidisciplinary
      approach involving orthodontics and prosthodontics. This case study demonstrates
      the management of a discrepancy in maxillary and mandibular anterior tooth
      widths. The problem is resolved by limited orthodontic treatment followed by
      porcelain laminate veneers. Anterior spacing is one of the major reasons adults
      seek esthetic treatment. Multidisciplinary treatment (periodontics, orthodontics
      and/or prosthodontics) is often indicated for an optimal result.

PMID- 11992944
TI  - Indirect provisionalization.

PMID- 11992943
TI  - Bone dynamics of osseointegration, ankylosis, and tooth movement.
AB  - Masticatory function challenges the strength and adaptive capability of
      supporting bone. When osseous tissue is loaded, it accumulates fatigue damage
      which must be repaired by bone modeling and remodeling. The three principal
      masticatory abutments (normal teeth, ankylosed teeth and osseointegrated
      implants) are a dynamic physiologic continuum relative to bone biomechanics.
      Implants are rigidly integrated units that can only be moved by fracturing the
      interface. Normal teeth and some ankylosed teeth can be moved using implants for
      orthodontic and orthopedic anchorage. Because orthodontic translation generates
      new bone and attached gingiva, it is a form of tissue engineering. Modern
      interdisciplinary practice requires a thorough knowledge of the principles of
      bone physiology and biomechanics.

PMID- 11992945
TI  - Dental assistants of Indiana: comments from the front lines.
AB  - During the summer of 1996, a random sample survey of 1500 Indiana dental
      assistants licensed in radiology by the Indiana State Board of Health was
      conducted. Surveys were mailed to participants, and follow-up postcard reminders
      were sent out a few weeks later. There were 569 surveys returned, representing a
      38 percent return rate. Numerical data were coded and entered in an SPSS program,
      and written comments were analyzed independently by the co-authors. Major
      demographic data and many categories of open-ended comments are summarized and
      analyzed in this paper. Results from this survey underscore the necessity for
      wages being improved in the dental assisting field. Comments underscore the fact
      that many dental assistants are not satisfied with their jobs and therefore may
      not be committed to either their careers or their employers. Office climate and
      relationships with the dentist are also described as being very important.

PMID- 11992946
TI  - Implant-aided treatment and root replacement therapy: a different look at implant
      dentistry.

PMID- 11992947
TI  - Osseointegration of tissue functional rough TiO2-blasted titanium implants: one
      year follow-up of 100 implants.

PMID- 11992948
TI  - [Etiology of fever in patients during inpatient care].

PMID- 11992949
TI  - [When is admission of geriatric patients to the intensive care unit justified?].

PMID- 11992950
TI  - [Pain in the back and neck].

PMID- 11992951
TI  - [Clinical significance of infections in geriatric patients in long-term nursing
      care facilities].

PMID- 11992952
TI  - [Affective climate. Dressing change].

PMID- 11992953
TI  - [Behavior in familial breast carcinoma].

PMID- 11992954
TI  - [AZUVITAL--a needs oriented geriatric concept. New methods in geriatrics].

PMID- 11992956
TI  - [Background information. Decubitus ulcer--development and prevention].

PMID- 11992955
TI  - [Drug compliance in elderly patients].

PMID- 11992957
TI  - [Combined drug-behavior therapy concept. When every swallow can be one too many].

PMID- 11992958
TI  - [Are sleep disorders trivialized?].

PMID- 11992959
TI  - The use of BoneSource for sinus floor augmentation with simultaneous implant
      placement in the atrophic maxilla. Interview by Arun K. Garg.

PMID- 11992960
TI  - The use of bioactive glass particles of narrow size range in the third molar
      site. Interview by Arun K. Garg.

PMID- 11992962
TI  - [Towards creation of an Alzheimer's care network].

PMID- 11992963
TI  - [Infection risks in geriatrics].

PMID- 11992964
TI  - [Epidemiology. Infections in geriatrics].

PMID- 11992965
TI  - [Epidemiology. Epidemics of Clostridium difficile in geriatrics].

PMID- 11992966
TI  - [Nursing strategy. The prevention of multiresistant bacteria dissemination].

PMID- 11992967
TI  - [Quality of life role in the decision to isolate septic patients in geriatrics].

PMID- 11992968
TI  - [Surveillance of infectious risk in geriatrics].

PMID- 11992969
TI  - [The geriatric Inter-Clin of Public Assistance-Hospitals of Paris, a nursing
      service network in geriatric hospitals].

PMID- 11992970
TI  - [...and a Clin in nursing homes?].

PMID- 11992971
TI  - [Technique. The colonic stent].

PMID- 11992972
TI  - [Dietetics. Water and other beverages].

PMID- 11992973
TI  - [Self help groups in long term care].

PMID- 11992974
TI  - [Leg ulcers].

PMID- 11992977
TI  - [Personalized autonomy allocation, according to the law!].

PMID- 11992975
TI  - [Images, tool of dreams and vector of communication].

PMID- 11992978
TI  - [Nursing care project and home nursing care services: first year of the reform?].

PMID- 11992979
TI  - Current concepts in augmentation grafting of the maxillary sinus for placement of
      dental implants.

PMID- 11992980
TI  - Does stretching induce lasting increases in joint ROM? A systematic review.
AB  - BACKGROUND AND PURPOSE: Stretching (that is, interventions that apply tension to
      soft tissues) induces increases in the extensibility of soft tissues, and is
      therefore widely administered to increase joint mobility and reverse
      contractures. However, it is not clear whether the effects of stretching are
      lasting. A systematic review was conducted to determine if stretching (either
      self-administered, administered manually by therapists or by some external device
      such as a splint) produces lasting increases in the mobility of joints not
      directly affected by surgery, trauma or disease processes. METHOD: In order to
      determine the lasting effects of stretching, only studies that measured joint
      range of motion (ROM) at least one day after the cessation of stretching were
      included. MEDLINE (from 1966 to June 2000), EMBASE (from 1988 to June 2000), the
      Cochrane Controlled Trials Register and PEDro databases were searched, and
      citation tracking was used to identify randomized studies that met the inclusion
      criteria. Each study was rated by two independent assessors on the PEDro scale,
      which rated trials according to criteria such as concealed allocation, blinding
      and intention-to-treat analysis. RESULTS: Thirteen studies satisfied the
      inclusion criteria. All examined the effect of stretching (median number of
      stretch sessions = eight) on joint ROM in healthy subjects without functionally
      significant contractures. Four studies were of 'moderate' quality and the
      remaining nine were of 'poor' quality. The 'moderate' quality studies suggest
      that regular stretching increases joint ROM (mean increase in ROM = 8 degrees;
      95% CI 6 degrees to 9 degrees) for more than one day after cessation of
      stretching and possibly that the effects of stretching are greater in muscle
      groups with limited extensibility. CONCLUSIONS: The results of four 'moderate'
      quality studies show a convincing effect of stretching in people without
      functionally significant contracture. These findings require verification with
      high-quality studies. Lasting effects of intensive stretching programmes (for
      example, stretching applied for more than six weeks or for more than 20 minutes a
      day) or of stretching on people with functionally significant contracture have
      not yet been investigated with randomized studies.

PMID- 11992981
TI  - Can early extubation and intensive physiotherapy decrease length of stay of acute
      quadriplegic patients in intensive care? A retrospective case control study.
AB  - BACKGROUND AND PURPOSE: Respiratory complications remain a major cause of
      morbidity and mortality in the acute quadriplegic patient population. The
      literature has suggested that early insertion of a tracheostomy facilitated
      pulmonary management and an earlier discharge from the intensive care unit (ICU).
      Recently, a change in practice has meant that these patients are considered for
      extubation and intensive physiotherapy treatment, including an overnight on-call
      service, rather than tracheostomy. The aim of the present retrospective, case
      controlled study was to determine if either practice resulted in a difference in
      length of stay in intensive care and if an on-call physiotherapy service for
      these patients was cost effective. METHOD: A case control design was used.
      Between April 1997 and November 1999, seven patients who did not require a
      tracheostomy were identified; case control subjects were matched for severity
      with seven patients who did receive a tracheostomy. Length of stay in intensive
      care and on the acute ward, days from injury to fixation and the overall number
      of respiratory physiotherapy and night physiotherapy treatments were recorded.
      RESULTS: Five of the seven patients in the non-tracheostomy group received on
      call overnight physiotherapy treatment, with an average of five sessions over a
      total of three nights. This group's length of stay in an ICU was significantly
      less than patients who were tracheostomized (p = 0.02). The overall number of
      physiotherapy treatments between the two groups was not significantly different.
      CONCLUSIONS: The results of this study suggest that if extubation and intensive
      physiotherapy is undertaken for suitable patients, the length of stay in
      intensive care can be significantly reduced. This represents a considerable cost
      saving for ICUs and more than covers the added cost of providing an after hours
      on-call physiotherapy treatment service. A prospective evaluation is required to
      confirm these findings.

PMID- 11992982
TI  - What do Swedish physiotherapists feel about research? A survey of perceptions,
      attitudes, intentions and engagement.
AB  - BACKGROUND AND PURPOSE: Although the past decades have witnessed an increase in
      physiotherapy research, there remains a concern about the translation of research
      into clinical practice, a problem that to date has attracted relatively limited
      interest. The aim of the present study was to investigate perceptions and
      attitudes toward research, intentions to perform as well as actual engagement in
      research-related activities in a sample of Swedish physiotherapists. METHOD: A
      cross-sectional design was used, and 343 Swedish physiotherapists responded to a
      postal questionnaire (representing a response rate of 61.7%). Questions about
      research-related activities were measured on a Likert-type scale, whereas
      questions referring to attitudes toward research used a semantic differential
      scale. RESULTS: The physiotherapists considered research as an important part of
      their professional role. Reading research literature was perceived as the most
      important research activity, and all mean attitude ratings were on the positive
      side of the scale. High workload and lack of time were the most commonly
      mentioned barriers to participation in research-related activities. Although
      Swedish physiotherapists read a large variety of journals, they most frequently
      read in their own language. CONCLUSIONS: The physiotherapists in this study were
      generally positive about research, which offers hope for an increased use of
      evidence-based practice in the future. In order to facilitate this development,
      easily accessible summaries could be provided. A cultural change within the
      profession, allowing more time for reading and discussing research reports should
      be encouraged.

PMID- 11992983
TI  - Beneficial therapeutic effects of physical training and relaxation therapy in
      women with coronary syndrome X.
AB  - BACKGROUND AND PURPOSE: New types of illness are being identified continuously.
      Owing to the demands for evidence-based practice, physiotherapeutic interventions
      need to be investigated scientifically prior to application in a new patient
      population. Coronary syndrome X (syndrome X) is a chronic pain disorder with
      exercise-induced chest pain despite angiographically normal coronary arteries.
      Patients with syndrome X constitute a therapeutic problem with considerable
      residual morbidity associated with functional limitation and reduced quality of
      life. Therefore, the aim of the present study was to investigate the effects of
      physical training and relaxation therapy on exercise capacity and quality of life
      in patients with syndrome X. METHOD: A single-blind, randomized controlled trial
      design was used. Twenty-four female patients aged 41-65 years were randomly
      assigned to three groups: A, B and C. All groups were similar at baseline for
      physical fitness level. Group A performed physical training for eight weeks at
      50% of baseline VO2max and group B participated in relaxation therapy for eight
      weeks. Group C acted as control subjects without any intervention. Before and
      after the eight-week periods, subjects were assessed by means of several measures
      of exercise capacity and quality of life. RESULTS: The measured variables did not
      change in the control group during the eight weeks. VO2max (< 0.02), work rate (<
      0.002) and distance walked during six minutes (< 0.003) increased only after
      physical training. The tolerated exertion during six minutes of walking (< 0.05)
      and the health-related quality of life, measured both by the Stress and Crisis
      Inventory (SCI) and the Sickness Impact Profile (SIP) (< 0.04), improved after
      both physical training and relaxation therapy. The general coping capacity,
      measured by the Sense of Coherence (SOC) questionnaire, remained unchanged in all
      the groups. CONCLUSIONS: Female patients with syndrome X benefit from physical
      training in terms of exercise capacity and quality of life and from relaxation
      therapy in terms of quality of life.

PMID- 11992984
TI  - Chronic shoulder pain in stroke. Are we missing the acupoint?

PMID- 11992985
TI  - Clinical trials of patient oriented therapy.

PMID- 11992986
TI  - More support for hospital-based nursing programs.

PMID- 11992987
TI  - More support for hospital-based nursing programs.

PMID- 11992988
TI  - More support for hospital-based nursing programs.

PMID- 11992989
TI  - Family-centered practices can make your ED stand out.

PMID- 11992990
TI  - Would you recognize this pediatric disorder?

PMID- 11992991
TI  - Chemical warfare.

PMID- 11992992
TI  - An unusual sleep disorder.

PMID- 11992993
TI  - Low literacy skills needn't hinder care.

PMID- 11992994
TI  - A new option for CHF patients.

PMID- 11992995
TI  - The legal landscape of long-term care.

PMID- 11992996
TI  - Forensic photo reminds nurses why SANEs are needed.

PMID- 11992997
TI  - Nursing instructors almost drove a male student away.

PMID- 11992998
TI  - [Cor pulmonale: interaction with pulmonary hypertension, sleep apnea and lung
      diseases].

PMID- 11992999
TI  - [Value of anti-arrhythmia agents in treatment of tachycardic heart arrhythmias].

PMID- 11993000
TI  - [Dilated cardiomyopathy and myocarditis. Current diagnostic requirements and
      therapeutic possibilities].

PMID- 11993001
TI  - [Cardiac and vascular gene therapy in cardiology. Current status and future
      prospects].

PMID- 11993002
TI  - [Autonomic dysfunction in heart patients].

PMID- 11993003
TI  - [Therapy of ischemic and nonischemic heart failure. Current status and
      prospects].

PMID- 11993004
TI  - [Preclinical management of acute coronary syndrome].

PMID- 11993005
TI  - [Modern reperfusion management in acute myocardial infarct].

PMID- 11993006
TI  - [Therapy with adult stem cells in myocardial infarct].

PMID- 11993007
TI  - [Secondary prevention in postinfarct patients].

PMID- 11993009
TI  - Working in the TNA trenches.

PMID- 11993010
TI  - Nurse entrepreneurs. Setting and achieving new goals.

PMID- 11993011
TI  - Curriculum development at Mona--the management of change.

PMID- 11993012
TI  - HIV/AIDS in women, infants, children and adolescents in Jamaica. A further "call
      to action".

PMID- 11993013
TI  - Managing curricular change in the UWI medical schools.
AB  - The ideal operational curriculum is dynamic. It is alive, constantly responding
      to changes within the social milieu served by its programmes. The medical
      curriculum of the University of the West Indies (UWI) has not been readily
      responsive to its catchment society's changing needs. This lack of resilience has
      created both curricular and administrative problems that have remained unsolved.
      Now, at the threshold of the twenty-first century, many more fundamental
      curricular changes are imperative in the UWI medical programme if the Faculty of
      Medical Sciences (FMS) is to be able to withstand the territorial invasions
      imminent from the global digital institutions of the new age. The new changes
      that will place the medical curriculum in line with the demands of the new
      Information Age will also remove the obnoxious effects of the 'dual curriculum'
      question and related issues. The Change Formula (Ch = V x P x D > C) that has
      worked the corporate transformations and realignments of the late twentieth
      century is applied to the thoughts of a reformed management of the UWI medical
      curriculum, and its ability to break down walls of resistance to change and
      liberate the curriculum to full dynamism is discussed.

PMID- 11993014
TI  - The healing power of intercessory prayer.
AB  - Arising from an emerging world view in philosophy, it is argued that the mind can
      function beyond the individual and is not constrained by time and distance; it is
      in fact non-local. Prayer is cited as an example of non-local manifestation of
      consciousness. Dossey describes three distinct eras of medicine. The hallmark of
      Era 3 is the non-local mind and unexplained discoveries of distant healing and
      intercessory prayer. In researching the medical literature, Dossey discovered 130
      studies dealing with the efficacy of prayer as a healing treatment. Those studies
      disclosed that prayer had a remarkable effect not only on human beings, but also
      on many other things including bacteria, germinating seeds and animals. Some
      cases of distant manifestation of consciousness on non-humans are discussed en
      passant, but the focus of this paper is the healing power of intercessory prayer
      on humans. Two case studies are offered in support of the evidence for non-local
      healing and the question is asked whether there is no place in medicine for a
      multiple approach to healing. Further, if these reported studies of prayer
      therapies are meaningful, are physicians not using these additional treatments
      withholding something curative from their patients?

PMID- 11993015
TI  - Lower limb bypass for intermittent claudication. Is it really worth the risk?

PMID- 11993016
TI  - Initial experience with in-vitro fertilization technology in the English-speaking
      Caribbean.
AB  - This audit documents the first experience with in-vitro Fertilization technology
      in the English-speaking Caribbean. From 1996 to 2000, 121 cycles have been
      performed in 99 couples utilizing these techniques. After ovarian stimulation,
      1,103 oocytes were retrieved (average 9.1) and of these, 65% fertilized normally,
      with embryo transfer possible in 111 cycles. Twenty-one pregnancies were recorded
      (21.2% per patient and 18.9% per embryo transfer) and the live birth rate per
      patient was 12.1%. The trend was for the success rate to be better in patients
      under age 36 years.

PMID- 11993017
TI  - In vitro fertilization. The Jamaican experience.
AB  - In June 2000, twenty-eight infertile couples were treated by in vitro
      fertilization and embryo transfer at our initial assisted reproduction programme
      carried out in conjunction with Midland Fertility Services, Aldridge, Birmingham,
      England. A pre-requisite for treatment was that on day 3 of the menstrual cycle
      the levels of follicle stimulating hormone (FSH) and oestradiol (E2) should be <
      10 i mu/l and < 100 pg/ml respectively in the female partner. The ages of the
      women ranged from 26 to 42 years with a mean age of 35.5 years. Down regulation
      was carried out by using buserelin acetate 0.5 microgram subcutaneously from day
      21 of the cycle for 21 days. This process was completed when the ovaries and
      pituitary gland were quiescent and the endometrial thickness < 4 mm in diameter.
      On completion of down regulation the gonadotrophin hormone, pergonal (dosage of
      150-450 units) was used for ovarian hyperstimulation. A total of 294 oocytes
      (mean of 10.5, range 2-45) were retrieved of which 138 were fertilized (mean of
      4.9, range of 0-28). Twenty-four patients each received a mean of two embryos.
      Five patients (20.8%) had positive pregnancy tests. Three patients (0.1%)
      developed ovarian hyperstimulation syndrome (OHSS), one had the severe, and two,
      the mild form of the syndrome. All three cases were treated successfully. The
      success at the initial IVF controlled ovarian hyperstimulation augers well for
      the future of infertile couples seeking treatment at the Fertility Management
      Unit, The University of the West Indies, Jamaica.

PMID- 11993018
TI  - Effect of pregnancy on plasma lipid concentration in Trinidadian women. Result of
      a pilot study.
AB  - In Trinidad and Tobago, cardiovascular disease and Type 2 diabetes mellitus are
      important causes of morbidity and mortality, and birth weight is significantly
      less than reference standards. Lower birth weight is associated with increased
      risk of these diseases. Variation in birth weight is due, in part, to deposition
      of adipose tissue in the foetus during the last trimester at the same time that
      maternal plasma triacylglycerol (TAG) increases. We conducted a pilot cross
      sectional analysis of maternal plasma lipid status and birth weight in healthy,
      non-pregnant, primigravida Trinidadian women. Non-pregnant and pregnant women, in
      their second and third trimesters, and at term, were recruited at random from an
      antenatal clinic. Adult and umbilical cord plasma TAG, non-esterified fatty acids
      (NEFA) and phosphatidylcholine (PC) concentrations were determined from gas
      chromatographic analysis of fatty acids. Maternal height, weight, skinfold
      thickness and infant birth weight were measured. The infants born to Afro
      Trinidadian and Indo-Trinidadian women were of low to normal birth weight
      (medians 3.07 and 3.22 kg, respectively). At term, plasma TAG concentration was
      approximately two fold (p < 0.05) greater than for non-pregnant women. The
      increment between 30-34 weeks was 1.5 to 1.9 fold lower than reported in other
      populations. There was a strong relationship (r = 0.8771, p = 0.019) between
      maternal and cord plasma TAG and NEFA, but not PC concentrations. There was no
      significant relationship between maternal TAG concentration at term and birth
      weight. The result suggests an impaired ability to increase plasma TAG
      concentrations during late gestation.

PMID- 11993019
TI  - Classical cardiovascular risk factors in Trinidadian patients with type 2
      diabetes mellitus are not influenced by the level of plasma glycaemia.
AB  - The aim of this study is to assess the plasma glycaemia of patients attending the
      diabetes mellitus outpatients' clinics in Trinidad and to determine how different
      plasma glycaemia would affect cardiovascular disease (CVD) risk factors. One
      hundred and ninety-one patients (64 males, 127 females, mean age 56.6 +/- 0.8 yr)
      with Type 2 diabetes mellitus (mean duration 9.2 +/- 0.6 yr) attending diabetes
      mellitus clinics from January to April 2000 participated in the study.
      Anthropometric indices (weight, height, waist and hip circumferences) and blood
      pressure were measured and overnight fasting blood samples were collected for
      glycated haemoglobin (HbA1c), glucose, lipids (triglyceride, total cholesterol,
      LDL-cholesterol, HDL-cholesterol) and creatinine determinations. The patients
      were categorized into Group 1 ('well controlled'; HbA1c < 7.0%) and Group 2
      ('poorly controlled'; HbA1c > 7.0%). Although the majority (85%) of patients were
      poorly controlled', there were no significant differences in the age, duration of
      diabetes mellitus, body mass index and waist/hip ratios between the two groups of
      patients (p > 0.05). Similarly, the blood pressure and lipid (total cholesterol,
      HDL-cholesterol, LDL-cholesterol) levels did not differ between the two groups (p
      > 0.05) although triglyceride (1.4 +/- 0.1 vs. 2.2 +/- 0.1 mmol/L) levels were
      higher in patients in Group 2 compared with Group 1 (p < 0.05). Multiple linear
      regression analysis indicates that the levels of blood pressure, lipid and
      anthropometric parameters were not significantly dependent on the plasma
      glycaemia of the patients (p > 0.05). Analysis of the data has shown that the
      majority of patients with Type 2 diabetes mellitus attending primary care clinics
      in Trinidad had poor glycaemic control. The poorly controlled patients had
      similar levels of CVD risk factors to 'well controlled' patients although the
      former were potentially at greater risk of progressing to cardiovascular disorder
      than 'well controlled' patients.

PMID- 11993020
TI  - Echocardiographic findings in a contemporary Afro-Caribbean population referred
      for evaluation of atrial fibrillation or flutter.
AB  - Atrial fibrillation and/or flutter is the most common and the most significant
      cardiac arrhythmia in the Caribbean. This study is an attempt to determine the
      echocardiographic findings in a current, consecutive series of Afro-Caribbean
      patients referred for evaluation of atrial fibrillation and flutter. Between May
      1998 and June 2000, 50 patients (mean age 67 years, 58% male) had echocardiograms
      done. Measurements included left atrial dimension (LA), left ventricular end
      systolic dimension (LVESD), LV end-diastolic dimension (LVEDD), LV posterior wall
      thickness (LVPWT) and ventricular septal thickness (VST). Left ventricular
      ejection fraction (EF) was calculated. LA > 4 cm, LVPWT or VST > 13 mm, and LVEF
      < 50% were considered abnormal. Atrial fibrillation was seen in 92%, atrial
      flutter in 8%; 60% were chronic, 40% paroxysmal; 56% had congestive heart
      failure. The most frequent echocardiographic finding was LV hypertrophy (19/50,
      38%). Left ventricular systolic dysfunction was present in 12/50, 24% (25% with
      LV hypertrophy also). Valvular disease (abnormal appearing valve, no Doppler
      study), was seen in 9/50, 18%. Normal findings ("lone atrial fibrillation") were
      seen in 10/50, 20%. Increased LA dimension was seen in 39/50, 78%. Patients with
      lone atrial fibrillation were younger (mean 56 years) than those with valvular
      disease (mean 64 years), LV systolic dysfunction (mean 69 years) and those with
      LV hypertrophy (mean 72 years). Thus, LV hypertrophy, probably secondary to
      hypertension, is the most frequent echocardiographic finding, with LV dysfunction
      (such as seen in coronary artery disease) seen less often. Valvular disease and
      lone atrial fibrillation rates are similar to rates in developed countries.

PMID- 11993021
TI  - Severe neurological complications post-open heart surgery. The Jamaican
      experience.
AB  - During the period January 1994 to December 1999, a total of 395 patients--adults
      and children--underwent various types of open heart surgical (OHS) procedures.
      The age range of these patients was 10 days to 77 years. Most (43.5%) of these
      patients underwent valve replacement--first time and 'redo'--as a result of
      rheumatic heart disease of varying duration and severity. The other large group
      was the complex congenital heart abnormalities (16%), followed by the group that
      underwent repair of atrial septal defect (13%), coronary artery bypass graft
      (13%) and repair of ventricular septal defect (12%). Open valve repair (2%) and
      excision of atrial myxoma (0.5%) were uncommon OHS procedures. Nine patients
      (2.3%) developed severe neurological complications (NCs) post-OHS. These
      included: a short period (< 48 hours) of irritability and fluctuating
      consciousness level; seizure activity associated with hemisparesis and/or
      blindness; severe encephalopathy and vegetative state. Four patients showed
      complete recovery, but one died as a result of complications of the anti-seizure
      medication. Of the other five, four died as a result of the NCs, and one was
      discharged in a vegetative state. Such severe neurological complications after an
      otherwise successful cardiac surgery represent a devastating outcome for patients
      and their families, and the social and economic impacts are enormous. Several
      risk factors were identified. The main ones being mitral valve replacement (MVR),
      especially 'redo' surgery, female gender, age over 60 years, high New York Heart
      Association functional class and post-operative hypotension. However, the true
      incidence of NCs (gross and subtle) in the study group cannot be ascertained. A
      detailed, structured neurological and neuropsychiatric assessment, both pre- and
      post-operatively, is therefore needed to document the true incidence of this
      complication. There is also the need for public education, especially for those
      with valvular disease, in order to encourage changes in attitude and behaviour
      towards continued follow-up care and valve surgery, both first time and 'redo'.

PMID- 11993022
TI  - The mid-forearm arteriovenous fistula as vascular access for haemodialysis.
AB  - Successful chronic haemodialysis requires permanent vascular access. The Scribner
      procedure which utilizes an external arteriovenous shunt, the internal synthetic
      arteriovenous shunt and the direct arteriovenous fistula as described by Cimino
      and Brescia have all been used for haemodialysis. Of the three methods, the
      arteriovenous fistula is the most trouble-free and durable. However, as
      originally described and constructed in the distal forearm, the morbidity
      associated with this method is significant. The cubital fossa fistula has even
      more problems. The mid-forearm fistula was designed by the authors and has been
      used for chronic haemodialysis over the past eighteen years. This article
      compares the various methods of access used in the haemodialysis units of the
      University Hospital of the West Indies and the Kingston Regional Hospital. The
      mid-forearm fistula was found to have the lowest initial failure rate and was
      associated with fewer complications than any of the other methods used for
      access.

PMID- 11993023
TI  - Hand infections in Jamaica.
AB  - Empirical antibiotic treatment for hand infections is changing to single
      antibiotic therapy against Staphylococcus aureus in immunocompetent patients.
      Fifty-one patients treated surgically for hand infections were reviewed to assess
      the nature of infection in terms of site, organism, mechanism of injury, and
      antibiotic sensitivity of the organisms. Twenty-three per cent of patients had
      diabetes mellitus and were noted to be older than non-diabetics. Eighty-four per
      cent of non-diabetic patients had single organism infections, 59% involving S
      aureus. Fifty per cent of diabetic patients had multi-organism infection caused
      by gram positive and gram negative organisms. Patients stuck with a piece of wood
      also had multi-organism infections. Double antibiotic therapy is therefore
      advocated for patients with diabetes mellitus and all patients who had hand
      infections as a result of being stuck with a piece of wood. All others should
      have single antibiotic therapy with amoxycillin and clavulanic acid.

PMID- 11993024
TI  - Intrathecal pethidine as sole anaesthetic agent for operative procedures of the
      lower limb, inguinal area and perineum.
AB  - Intrathecal pethidine as a sole anaesthetic agent for surgical procedures of the
      lower limbs, perineum and inguinal areas was investigated and compared with
      hyperbaric Bupivacaine. A total of 90 patients were studied and randomly divided
      into groups 1 (bupivacaine) and 2 (pethidine). In group 2, 26 of 46 patients
      (59%) had their procedures successfully with intrathecal pethidine alone and did
      not require or request any additional sedation or analgesia. This compared to 24
      of 44 patients (52.2%) in the bupivacaine group. Pethidine had a prolonged
      postoperative analgesia and was more cost-effective. The incidences of side
      effects were acceptable. (hypotension 13.6%, bradycardia 9.09%, nausea and
      vomiting 11.4%, and pruritus 15.9%). Pethidine can be used as a sole anaesthetic
      agent for operative procedures of the lower limbs; side effects are mild and can
      be treated.

PMID- 11993025
TI  - Immunization status of thirty patients with sickle cell disease five years post
      hepatitis B vaccination. A comparison with normal controls.
AB  - In order for hepatitis B immunization programmes to be cost effective and
      clinically beneficial, vaccinated persons should maintain an immunity threshold
      titre of antibodies to hepatitis B surface antigen greater than 10 IU/l. Those
      who fall below this level should be boosted in order to be covered against the
      risk for which the vaccine was administered. Persons with sickle cell disease are
      included in the group for whom hepatitis B immunization is routinely prescribed.
      Antibody to hepatitis B surface antigen was measured in paired sera of thirty
      patients with sickle cell disease compared with a control group of healthy
      medical staff, five years post vaccination. There was no significant difference
      between patients with sickle cell disease and normal controls in the levels of
      antibody maintained or numbers that required booster vaccination. Recommendations
      for the maintenance of protection via revaccination should be the same for
      persons with sickle cell disease as for healthy persons.

PMID- 11993026
TI  - Identification of Anopheles aquasalis as a possible vector of malaria in Guyana,
      South America.
AB  - Adult female mosquitoes were collected in Mahdia, Guyana, to determine the
      incidence of malaria in Anopheles species found during the month of June 2000.
      Centers for Disease Control miniature white (incandescent) light traps, model
      512, and miniature black (ultraviolet) light traps, model 912, were used to
      capture female mosquitoes. Numbers of mosquitoes collected were compared between
      white and black light traps and between traps set outside and inside of
      buildings. Adult female Anopheles mosquitoes were identified and an ELISA
      dipstick test for Plasmodium vivax and Plasmodium falciparum was performed on
      each mosquito. An aquasalis, An oswaldoi, and An braziliensis were attracted to
      white light traps. An triannulatus and An darlingi were collected from black
      light traps. Approximately the same numbers of all female Anopheles mosquitoes
      28/45 (62%) were caught inside buildings as outside. Numbers of female non
      anopheles mosquitoes captured in light traps varied between the traps set outside
      of buildings and inside of buildings with bright light traps collecting 91/122
      (75%). A total of 45 Anopheles mosquitoes were captured and 122 non-anopheles
      species. Of the two known vectors of malaria in Guyana, An darlingi mosquitoes
      were not infected with P vivax but An aquasalis was found to be a carrier. The
      findings of this study suggest a need for further surveying and identification of
      current malaria vectors in Guyana.

PMID- 11993027
TI  - Quality of care in family planning clinics in Jamaica. Do clients and providers
      agree?
AB  - This paper uses data from 199 providers and 20 simulated clients collected at 50
      public sector and Non Governmental Organization (NGO) health facilities
      islandwide in 1995 to compare the two groups' views on quality of care of family
      planning services. Each of the five components of quality of care studied can be
      improved in Jamaica. Nearly two-thirds of the simulated clients felt able to
      freely choose a contraceptive method; however, more adequate and appropriate
      information needs to be imparted to clients through improved counselling,
      including promotion of dual method use (against STD/HIV/AIDS and conception). The
      requirement that a woman must be menstruating to receive services has
      inadvertently resulted in many clients going away empty-handed (without
      counselling or condoms) when they visit family planning clinics. While providers
      generally treat clients well, training and service delivery practices need to be
      revised to improve the technical competence of providers. All of the providers
      would recommend these clinics to others, compared to a little over half of the
      simulated clients. Both the providers and simulated clients said that privacy
      should be strengthened, particularly in small facilities in rural areas. Many of
      these aspects of quality of care are being improved in Jamaica's public sector
      health facilities. Managers can learn more about quality of care by seeking the
      knowledge, opinions and experiences of both providers and clients.

PMID- 11993028
TI  - Extrapelvic endometriosis presenting as unusual swellings of the buttock and
      thigh.
AB  - We present the first case of extrapelvic endometriosis (EPE) presenting as
      combined swellings of the thigh and buttock in a 28-year-old nulliparous woman.
      The diagnosis was aided by the history of cyclical symptoms, needle aspirate,
      ultrasonography and computed tomography scan and was confirmed by histological
      analysis of the excised specimens. Of note, laparoscopy showed the pelvis to be
      free of gross disease. Surgical excision combined with hormonal suppression
      therapy proved adequate treatment in preventing recurrence as well as the
      complications of wound implantation.

PMID- 11993029
TI  - Images and diagnoses. Lipoma.

PMID- 11993030
TI  - Images and diagnoses. Aneurysmal bone cyst.

PMID- 11993031
TI  - Images and diagnoses. Lichen planus.

PMID- 11993032
TI  - Cardiac rhabdomyoma in infancy. A case report.
AB  - We describe a case of rhabdomyoma of the heart in a newborn infant and present an
      overview of current knowledge about the natural history of these lesions, with
      implications for management. This is the only case of its kind seen at this
      hospital.

PMID- 11993033
TI  - Ataxia Telangiectasia. A case report.
AB  - The case of an eight year old girl with Ataxia Telangiectasia (AT) is described.
      She presented at seven years of age with gait problems and was found to have the
      neurological, dermatological and immunological features characteristic of AT
      along with a history of frequent sino-pulmonary infections. This report
      highlights the refractory nature of the disease, the difficulties in medical
      management, and the problems posed by late diagnosis which can compromise patient
      care. This is a rare inherited form of ataxia which has not been previously
      reported in West Indian literature.

PMID- 11993034
TI  - Successful pregnancy after frozen embryo transfer.

PMID- 11993035
TI  - Isolated torsion of a haematosalpinx in a virginal girl.

PMID- 11993036
TI  - The struggle between evidence and quality.

PMID- 11993037
TI  - The future of medicine.

PMID- 11993038
TI  - Treating obesity.

PMID- 11993039
TI  - Treating obesity.

PMID- 11993040
TI  - Five tips for less costly flu vaccination.

PMID- 11993041
TI  - Docs expected to refuse new Medicare patients due to payment cuts.

PMID- 11993042
TI  - Why we're in the mess we're in.

PMID- 11993043
TI  - Ideas for managing stress and extinguishing burnout.

PMID- 11993044
TI  - Building a mind set of service excellence.

PMID- 11993045
TI  - A tool for better well-woman exams.

PMID- 11993046
TI  - How much will that EMR system really cost?

PMID- 11993047
TI  - Putting politeness into practice.

PMID- 11993048
TI  - Managing at a distance: five fundamentals of effective leadership from afar.

PMID- 11993049
TI  - Hiring hints: first impressions are important.

PMID- 11993050
TI  - Point: administration's focus on health remains near-sighted.

PMID- 11993051
TI  - Counterpoint: heavy-handed policy won't help solve health care problems.

PMID- 11993052
TI  - Trend note: HMO enrollment tumbles in 2001.

PMID- 11993053
TI  - In disaster's aftermath, don't forget the needs of employees.

PMID- 11993054
TI  - New HCPCS codes for ostomy supplies.

PMID- 11993055
TI  - Recognizing spiritual distress.
AB  - Recent research suggests that while attending worship services may extend life,
      spiritual distress may cut lives shorter. Although authors of this research agree
      that more study is needed, they recognize that elderly ill men and women who
      experience a religious struggle with their illnesses appear to be at risk for an
      earlier death, even after controlling for baseline health, mental health, and
      demographic factors. This article examines the patient-professional relationship
      within the framework of virtue ethics and spiritual distress. A case study is
      presented.

PMID- 11993056
TI  - The power of many, the power of two.

PMID- 11993057
TI  - Reducing epibole using topical hyperbaric oxygen and electrical stimulation.

PMID- 11993058
TI  - Woundoscopy: a new technique for examining deep, nonhealing wounds.
AB  - This article discusses a standard gastrointestinal procedure used to visualize
      sinus tracts in wounds. Sinus tracts have traditionally been visualized
      externally and probed internally. Because of this, the cause of the nonhealing
      wound was difficult to determine. Through a series of case studies performed at
      St. Francis Hospital Wound Care Institute, the authors documented the benefits to
      patients of a technique they call woundoscopy--endoscopy performed to gain
      additional information about wounds that have not healed by standard therapies.
      These benefits include early diagnosis and treatments less traumatic than
      traditional surgical incision and intervention. Although not a procedure to be
      used indiscriminately, woundoscopy resulted in positive outcomes. Further
      research seems warranted.

PMID- 11993059
TI  - A premature infant with skin injury successfully treated with bilayered cellular
      matrix.
AB  - The immature skin of premature infants is functionally less effective than the
      skin of full-term infants and therefore more vulnerable to injury. This article
      discusses the use of a biologic wound healing agent--bilayered cellular matrix-
      to heal a denuded hip wound in a premature infant. The treatment involved a
      compassionate use, single application of an investigational biologic wound
      healing agent to a 2.0-cm x 1.5-cm hip wound in a 23-week gestational age
      premature infant. A sterile, nonadherent dressing containing 3% bismuth
      tribromophenate in a special petrolatum blend on a fine mesh gauze also was
      applied over the biologic dressing and changed as needed. Wound closure was
      evaluated by photographs taken before and after the application of the bilayered
      cellular matrix. Wound measurements were reduced to 1.0 cm x 0.5 cm by day 4 post
      application of the bilayered cellular matrix, and clean granulation tissue was
      present. The wound was healed 10 days later. No signs or symptoms of infection
      were evident during the follow-up period and no adverse events were recorded.
      Comparative studies are warranted to fully evaluate the utility of bilayered
      cellular matrix in this clinical setting.

PMID- 11993060
TI  - Efficacy of pulsed low-intensity ultrasound in wound healing: a single-case
      design.
AB  - Therapeutic ultrasound is used clinically to enhance healing of pressure ulcers.
      Limited clinical research is available and no consensus exists regarding the
      efficacy of ultrasound for treating pressure ulcers, particularly full-thickness
      pressure ulcers, in the elderly. To assess the efficacy of pulsed low-intensity
      ultrasound on wound healing, a double-blind, single-case, baseline-AB study was
      conducted. The participant, a patient in a skilled nursing facility, was a 75
      year-old woman with a Stage III pressure ulcer over the coccyx. Pulsed low
      intensity ultrasound was compared to placebo ultrasound. After the 1-week
      baseline period, each ultrasound treatment was administered 5 days a week for two
      consecutive weeks. Throughout the baseline and ultrasound treatment periods, the
      patient additionally received the standard wound care treatment program at the
      facility. The rate of wound surface area reduction was used as the measure of
      wound healing. Healing was significantly faster (P = 0.001) during the pulsed low
      intensity ultrasound period (34.0 mm2/day) compared to the placebo ultrasound
      period (12.6 mm2/day), but was significantly faster (P = 0.001) during the
      baseline period (50.8 mm2/day) compared to the pulsed low-intensity ultrasound
      period. Healing in this patient was faster than rates noted in the literature
      under similar conditions. The precise effect of either ultrasound intervention in
      this study could not be determined. Neither pulsed low-intensity ultrasound nor
      placebo ultrasound likely had an appreciable effect on healing of this patient's
      pressure ulcer beyond that of the standard-care protocol.

PMID- 11993061
TI  - A comprehensive program to prevent pressure ulcers in long-term care: exploring
      costs and outcomes.
AB  - With scrutiny from survey agencies (Centers for Medicare and Medicaid Services
      and state agencies) and potential litigation increasing, long-term care
      facilities must implement aggressive pressure ulcer prevention programs. However,
      cost-effective pressure ulcer prevention continues to be a challenge for most
      long-term care facilities, in part because limited research is available to guide
      their efforts. Two long-term care facilities (Facility A with 150 beds and
      Facility B with 110 beds) participated in a quasi-experimental study using
      retrospective and prospective study data to evaluate the effect of implementing a
      protocol of care to address the incidence of pressure ulcers. Retrospective study
      results showed a combined, cumulative, 5-month pressure ulcer incidence of 43% in
      Facilities A and B. Implementation of the comprehensive prevention program
      resulted in an 87% decrease in pressure ulcer incidence in Facility A (from 13.2%
      to 1.7% per month, P = 0.02) and a 76% decrease in Facility B (from 15% to 3.5%
      per month, P = 0.02). The average monthly cost of prevention for a high-risk
      resident was $519.73 (plus a one time cost of $277 for mattress and chair
      overlays). More than half ($277.15) of the monthly costs relates to labor; the
      most expensive item cost is for support surfaces. This study demonstrated that
      this comprehensive program resulted in a significant decrease in the incidence of
      pressure ulcers in two long-term care facilities. Because labor and support
      surface costs remain high, long-term care facilities are encouraged to use
      prevention intervention strategies based on risk stratification.

PMID- 11993062
TI  - Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic
      foot.
AB  - The purpose of this retrospective study was to evaluate outcomes of people with
      large diabetic foot wounds treated with subatmospheric pressure dressing therapy
      immediately following surgical wound debridement. Data were abstracted from the
      medical records of 31 consecutive patients with diabetes, 77.4% male (n = 24),
      aged 56.1 +/- 11.7 years, presenting for care at two large multidisciplinary
      wound care centers. All patients received surgical debridement for indolent
      diabetic foot wounds and were subsequently started on a regimen of subatmospheric
      pressure dressing therapy delivered using a vacuum-assisted closure device for a
      mean of 4.7 +/- 4.2 weeks (mode = 2 weeks) using a protocol that called for
      cessation of therapy when the wound bed approached 100% coverage with granulation
      tissue with no exposed tendon, joint capsule, or bone. Outcomes evaluated
      included time to complete wound closure, proportion of patients achieving wound
      healing at the level of initial debridement, and complications associated with
      use of the device. The mean duration of wounds before therapy was 25.4 +/- 23.8
      weeks. In patients treated with subatmospheric pressure dressing therapy, 90.3%
      (n = 28) of wounds healed at the level of debridement without the need for
      further bony resection in a mean 8.1 +/- 5.5 weeks. The remaining 9.7% (n = 3)
      went on to higher level amputation (below knee amputation = 3.2%, [n = 1] and
      transmetatarsal amputation = 6.5% [n = 2]). Complications included periwound
      maceration (19.4% [n = 6]), periwound cellulitis (3.2% [n = 1]), and deep space
      infection (3.2% [n = 1]). The authors concluded that appropriate use of
      subatmospheric pressure dressing therapy to achieve a rapid granular bed in
      diabetic foot wounds may have promise in treatment of this population at high
      risk for amputation and that a large, randomized trial is now indicated.

PMID- 11993063
TI  - From proposal to patient: how CMS makes coverage decisions.

PMID- 11993064
TI  - Psychological impact of the physician-patient relationship on compliance: a case
      study and clinical strategies.
AB  - This article presents a case of a heart transplant recipient's noncompliance. A
      patient's probable medical compliance is among the primary psychosocial criteria
      in determining his or her eligibility for a heart transplant. The ability to
      predict and facilitate patient compliance remains a challenge to physicians in
      all areas of medicine and surgery. The accuracy of the compliance prediction is
      often contingent upon information generated by patient interviews, other medical
      personnel, and the patient's family members. All too often, this vital
      information is based on subjective data, creating difficulty for physicians in
      appraising patient compliance behavior. Such an amorphous data gathering process
      may leave physicians at a loss to explain the nature and extent of their
      patients' behaviors. Research has yet to provide consistent objective measures
      for compliance prediction. Patient compliance affects all corridors of medical
      practice and is responsible for an innumerable loss of human life, and financial
      resources each year.

PMID- 11993065
TI  - Drug-induced gingival hyperplasia in transplant recipients.
AB  - Gingival hyperplasia is a common occurrence in transplant recipients who are
      taking cyclosporine. This condition can be complicated when calcium channel
      blockers or phenytoin are added to the armamentarium of medications; it can be
      painful and may interfere with eating, speech, and appearance. Multiple
      mechanisms exist for gingival overgrowth. Prevention with appropriate oral
      hygiene appears important in controlling the inflammatory component and
      decreasing the severity of the overgrowth. Patients must be aware of the
      potential for the development of gingival hyperplasia and must follow up with
      regular professional cleanings. If the overgrowth persists, treatment options
      should be discussed between patients and their physician. Conversion from
      cyclosporine to tacrolimus, treatment with antibiotic therapy, and surgical
      excision or laser therapy are all potential therapies to consider.

PMID- 11993066
TI  - Health locus of control and adherence with home spirometry use in lung transplant
      recipients.
AB  - Home monitoring is an effective tool that can be used to promote the health of
      lung transplant recipients, but only if the recipients transmit data to the
      healthcare team. This study examines the relationship of the Multidimensional
      Health Locus of Control scale to adherence with home spirometry use. Form C of
      this scale was mailed to 139 eligible lung and heart-lung transplant recipients.
      Eighty-three respondents returned the questionnaire. The respondents were on
      average 4 years older and had greater adherence than nonrespondents. Men tended
      to score higher than women on all the subscales. These scales were not related to
      type of transplant or underlying disease. Adherence was also unrelated to the
      Multidimensional Health Locus of Control scale, with little difference in
      adherence across persons with various levels of the health locus of control
      subscales.

PMID- 11993067
TI  - Evaluation guidelines for adult and pediatric kidney transplant programs: the
      Missouri experience.
AB  - CONTEXT: Rigorous candidate evaluation is paramount for estimating risk and long
      term success with transplantation. In addition, because of increasing waiting
      times, patients are seeking listing at multiple centers or transferring waiting
      time from one center to another. Variations in center evaluation criteria are
      becoming increasingly important to patients. OBJECTIVE: To describe the
      similarities and differences among the evaluation guidelines for adult and
      pediatric kidney transplant programs in Missouri. DESIGN: A descriptive design
      was used. SETTING AND PARTICIPANTS: Kidney transplant nurse coordinators from 7
      adult and 4 pediatric kidney transplant programs from 10 centers in Missouri were
      invited to submit the kidney transplant candidate evaluation guidelines from
      their programs. RESULTS: Guidelines were submitted by nurse coordinators from all
      programs. Consults with the kidney transplant team members, including surgeon,
      nephrologist, social worker, and nurse coordinator, were included in all of the
      programs. For the adult programs, 67% (20/30) of the tests and laboratory values
      were agreed on by at least 70% of the program transplant team members. Similarly,
      for the pediatric programs, 62% (16/26) of the age-appropriate tests and
      laboratory values were agreed on by at least 75% of the program transplant team
      members. CONCLUSIONS: Within the Missouri programs, testing is consistent whether
      the center is large or small, adult or pediatric. Transplant teams should
      periodically review their kidney transplant recipient evaluation criteria for
      similarities to and differences from the current state-of-the-science and
      surrounding programs.

PMID- 11993068
TI  - Living-related liver transplantation: a Thai family's stressors and concerns.
AB  - This case study reviews the experience of a Thai family who traveled to Japan for
      living-related liver transplantation. The recipient experienced multiple problems
      after transplantation, which placed additional stress on the family. The cultural
      gap and language barrier resulted in a lack of understanding and often made it
      difficult for the medical team and family to communicate effectively. However,
      the use of interpreters helped to resolve these problems. This study shows that
      it is especially important for transplant coordinators and social workers to
      facilitate the collaboration and understanding between families and the medical
      team when cultural and language differences exist.

PMID- 11993069
TI  - Tissue donation: what does it mean to families?
AB  - CONTEXT: Previous research has described families' responses and experiences with
      the donation process; however, little attention has been paid to families linked
      to tissue banks that have no affiliation with hospitals or organ procurement
      agencies. OBJECTIVE: To assess the impact of approaches made to families who
      consented to tissue donation with the Donor Tissue Bank of Victoria, Australia,
      and to examine how this information could be used to improve the existing
      service. DESIGN: An evaluation questionnaire was developed and consisted of 15
      questions. The questionnaire was part of a structured follow-up service and was
      given only to 339 families who consented to donation. SETTING AND PARTICIPANTS:
      Families who are approached about tissue donation are contacted within 24 hours
      of their family member's death. They are coping with the sudden unexpected death
      of a family member and have little knowledge of tissue donation or the donor
      tissue bank. MAIN OUTCOME MEASURES: Fifty-eight percent of participants completed
      the questionnaire. The data were quantitatively and qualitatively examined.
      RESULTS: The skills and procedures utilized by the transplant coordinators are
      affirmed by the results, and respondents appear to find contact with the donor
      tissue bank positive at a terrible time in their lives. Approaches to families
      must be made sensitively and sufficient information must be given to enable
      decision making.

PMID- 11993070
TI  - What ails cadaveric transplant programs in India: perspectives of a transplant
      coordinator.
AB  - In India, the success of a cadaveric transplant program is limited by the number
      of available organs. Major reasons for this organ shortage include ignorance and
      misconceptions about brain death and the organ retrieval process; mistrust in the
      medical system; fear of mutilation of the body, delay in the funeral ceremonies,
      and mistreatment in the hospital if the patient has pledged organs following
      death; nonexistence of an organ procurement agency; and an ineffective organ
      retrieval and sharing network. Nonexistence of efficient organ coordination is an
      important factor in the organ shortage. Now, as organ transplant programs are
      being conceived and implemented in full earnest, transplant coordinators must be
      included as an indispensable component. Their role will be to educate the public,
      act as a liaison between the hospital and the society, and coordinate the process
      of organ procurement by taking consent of grieving relatives of brain dead
      persons.

PMID- 11993072
TI  - Conducting and publishing research: responsibilities of authors and journals.

PMID- 11993071
TI  - Decoupling: what is it and does it really help increase consent to organ
      donation?
AB  - Although the notion of decoupling is simple and potentially controllable by organ
      donation requestors, evidence to date of its potential has been inconsistent. The
      impact of the timing of requests was analyzed using data from a study of organ
      donor-eligible patients and their families (N = 420), involving 9 trauma
      hospitals located in southwest Pennsylvania and northeast Ohio. In-depth
      interviews where conducted with family members, healthcare professionals, and
      organ procurement organization staff involved in the process. Only a weak effect
      was found for the impact of timing on the decision using a bivariate,
      correlational analysis. Moreover, we found that raising the issue before rather
      than after the pronouncement of death was most strongly associated with consent
      to donation. This effect disappeared after examining decoupling in relation to
      other factors. However, active consideration of the patient's donation wishes and
      a clear understanding of the families' initial inclination toward donation were
      associated with consent to organ donation.

PMID- 11993073
TI  - A review of "chest tubes" during donor care and after transplantation.
AB  - Thoracostomy tubes, also called chest tubes, are commonly present after
      transplantation or during donor care. The function of the thoracostomy tube is to
      provide a conduit for transporting fluid, gas, or blood from the pleural cavity
      to an attached drainage unit. Malfunction of the tube or parts of the unit
      assembly may lead to serious consequences and jeopardize transplant recipient
      recovery or donor organs. This review discusses the components of the
      thoracostomy tube and drainage unit assembly, normal operation, routine
      evaluation, and common problems that the organ procurement or transplantation
      coordinator may need to anticipate or treat.

PMID- 11993074
TI  - Resources for patients. Transplant medications--Part 1: An overview.

PMID- 11993075
TI  - Cultural analysis of an organ procurement organization.

PMID- 11993076
TI  - [Clear demarcation of the responsibility for the operative positioning of
      patients results in greater security].

PMID- 11993077
TI  - [Allocation of responsibility for positioning patients for surgery and liability
      for damages consequent on faulty positioning].
AB  - The cooperation of surgeon and anaesthetist in positioning of the patient is
      subject to the principles of horizontal division of labour recognized in the
      interdisciplinary agreement and confirmed by the legislature: anaesthetist and
      surgeon carry out their respective tasks independently of each other, each
      bearing full responsibility for their own work (principle of strict separation of
      functions), they tailor their procedures to fit in with each other (duty of
      coordination), and each is entitled to expect and rely on due care in the other
      (principle of trust). In the case of conflict--when the best position for the
      specific intervention leads to a higher anaesthesiological risk--the principle of
      predominance of the actual requirements applies. If no agreement is reached it is
      incumbent on the surgeon to make the decision; this means that the surgeon bears
      the medical and legal responsibility for appropriate deliberation. Faults in
      organization are regarded under the law as faulty treatment. Anaesthetist and
      surgeon are each responsible for their own errors. According to the
      interdisciplinary agreements, positioning and checks on position are the task of
      the surgeon, while the anaesthetist is responsible for the "infusion arm". This
      does not exclude the possibility that anaesthetist and surgeon may agree on a
      different division of labour in the operating room. The patient bears the burden
      of proof that errors were committed in a case for damages. The doctor does,
      however, have to prove that the patient was correctly positioned. The demands of
      jurisdiction in terms of documentation of the positioning and of presentation of
      evidence are practically oriented and can basically be met. The same is true of
      the information supplied to the patient on the risk that positioning can cause
      harm. The doctor is obliged to supply evidence of the patient's substantive
      consent and the provision of information that this implies.

PMID- 11993078
TI  - [Postoperative pain therapy in minimally invasive direct coronary arterial bypass
      surgery. I.v. opioid patient-controlled analgesia versus intercostal block].
AB  - OBJECTIVE: Lately introduced cardiosurgical procedures such as MIDCAB enable an
      early extubation immediately after surgery. This also requires an adequate
      anesthesia regime and especially a sufficient postoperative analgesia. Patient
      controlled analgesia (PCA) and intercostal nerve blockade (ICB) were evaluated
      for their suitability for postoperative pain relief in patients undergoing a
      MIDCAB procedure. MATERIAL AND METHODS: After approval by the local ethic
      committee and obtaining written informed consent 43 patients were included in
      this study. Anesthesia was induced and maintained in a total intravenous
      standardised manner with propofol, remifentanil, cisatracurium and additionally
      glyceroltrinitrate, clonidine and esmolol were given as needed. After
      revascularisation patients were randomly assigned to one of two groups receiving
      either 7.5 mg piritramid i.v. before extubation and continuing a PCA with 2 mg
      boli and a 10 min lockout, or an ICB with ropivacaine 1% (4 times 5 ml).
      Additionally all patients received 1 g paracetamol rectally before induction of
      anesthesia and 1 g metamizol i.v. at the end of surgery. A rescue medication of
      3.75 mg piritramid i.v. was allowed. A pain score (NRS 0-10), the Aldrete score
      (AS 0-12) and oxygen saturation were obtained 1, 4, and 8 h after extubation.
      RESULTS: The ICB group showed a significantly greater pain reduction in the first
      (5.8 +/- 1.8 vs. 7.3 +/- 1.9; P < 0.02) and fourth h (3.6 +/- 1.3 vs. 4.6 +/-
      1.4; P < 0.02), respectively. Transfer to an intermediate care ward one hr after
      extubation was achieved more often in the ICB group according to the AS (ICB 9.6
      +/- 1.5 vs. PCA 8.9 +/- 1.2; P < 0.05), too. There was no difference with respect
      to the oxygen saturation. The additional piritramid demand was 9.3 mg in the ICP
      group and 5 mg in the PCA group in the first 8 hours postoperative. CONCLUSION:
      ICB gives a better pain relief in the early postoperative phase after MIDCAB
      procedures compared to a PCA. Both regimes are adequate in order to provide a
      sufficient pain relief and help to avoid prolonged postoperative mechanical
      ventilation. These will enable an early transfer of patients to an intermediate
      care station and save ICU capacity.

PMID- 11993079
TI  - [Analysis of the anesthesiologist's vigilance with an eye-tracking device. A
      pilot study for evaluation of the method under the conditions of a modern
      operating theatre].
AB  - INTRODUCTION: With the inclusion of new monitoring devices over the last two
      decades, the distribution of the anesthesiologists vigilance has changed which
      might influence the ergonomic profile of an optimal anesthesia workstation. The
      aim of this pilot study was the evaluation of an eyetracking device to analyze
      the vigilance distribution of an anesthesiologist during routine cases in an
      operating theatre of the 21st century. MATERIAL AND METHODS: Five
      anesthesiologist with different levels of training were followed during different
      types of surgery using a video camera-based eye-tracking system. The films were
      analyzed by an independent observer and rated according to defined regions of
      interest (ROI). Then typical scan-paths were identified and quantitatively
      analyzed. RESULTS: The eye-tracking studies proved to be technically of high
      quality but were time-consuming. Only few disturbances to the operating room (OR)
      personnel were recorded according to their subjective impressions but bias of
      behaviour due to the measurement procedure itself cannot be completely excluded.
      The vigilance of the anesthesiologist towards different factors was dependent on
      the level of professional training, the type of anesthesia and the type of
      surgery. Certain factors such as documentation (10-15%) or external disturbances
      (approximately 20%) proved to be relatively constant. Typical scan-paths could
      also be identified. CONCLUSION: Eye-tracking studies proved to be a suitable way
      to analyze the distribution of vigilance of anesthesiologists in a modern
      operating theatre. For further studies examining the influence of detailed
      modifications of the OR environment, a standardized study design with the same
      level of education, the same anesthesia technique and the same surgical procedure
      needs to be chosen.

PMID- 11993080
TI  - [Anaphylactic shock following intravenous hydrocortisone succinate
      administration].
AB  - Glucocorticoids are frequently used in clinical anaesthesiology and intensive
      care because of their antiallergic, antiinflammatory and antioedematous
      properties and anaphylactic reactions are rare. We report on a 62-year-old
      asthmatic patient with evidence of aspirin sensitivity. We administered 100 mg of
      hydrocortisone-21-hemisuccinate (Pharmacia & Upjohn, Erlangen, Germany) dissolved
      in 100 ml 0.9% sodium chloride solution for perioperative corticoid substitution.
      The patient immediately developed severe bronchospasm and anaphylactic shock
      requiring intubation and mechanical ventilation. He received adrenaline,
      isoflurane, ketamine and inhalational fenoterol. He then developed
      atrioventricular block type III for which we transcutaneously paced the patient.
      Subsequently he was tested via skin prick tests, intracutaneous tests and i.v.
      challenges resulting in the patient having positive reactions to hydrocortisone
      21-hemisuccinate. Thus when allergic-like reactions result from glucocorticoid
      therapy one should consider corticoid allergy as a differential diagnosis.

PMID- 11993081
TI  - [The use of arginine vasopressin during cardiopulmonary resuscitation. An
      analysis of experimental and clinical experience and a view of the future].
AB  - The risks and benefits of epinephrine given during cardiopulmonary resuscitation
      (CPR) are controversially discussed. Animal experiments revealed beta-receptor
      mediated adverse effects of epinephrine such as increased myocardial oxygen
      consumption, ventricular arrhythmia, ventilation-perfusion defects, and cardiac
      failure in the postresuscitation phase. In clinical studies, high-dose vs.
      standard-dose epinephrine was unable to improve resuscitation success. During CPR
      in patients, endogenous arginine vasopressin (AVP) levels were increased and
      surviving vs. non-surviving patients had significantly higher AVP levels. This
      may indicate that the human body discharges AVP during life-threatening
      situations as an additional vasopressor to catecholamines in order to maintain
      cardiocirculatory homeostasis. In different experimental CPR models, AVP compared
      with epinephrine given during CPR significantly improved vital organ blood flow,
      coronary perfusion pressure, resuscitability, and long-term survival. During
      prolonged CPR with repeated drug administration, AVP but not epinephrine
      maintained coronary perfusion pressure on a level that ensured return of
      spontaneous circulation. Also, AVP can be administered successfully in the
      intravenous dose into the endobronchial tree, and also intraosseously. When given
      during CPR, AVP induces a transient splanchnic hypoperfusion, and an increase in
      systemic vascular resistance, both of which normalized spontaneously;
      furthermore, an oligo-anuric state was not observed. In two clinical studies, AVP
      vs. epinephrine improved 24-h survival during out-of-hospital CPR, and comparable
      CPR outcome during in-hospital CPR. The new CPR guidelines of both the American
      Heart Association and the European Resuscitation Council assign a given CPR
      intervention into classes of recommendation [class 1 (definitely recommended),
      class 2 A (intervention of choice), class 2B (alternative intervention), class X
      (neutral), or class 3 (not recommended)]. For CPR of adults with shock-refractory
      ventricular fibrillation, 40 units AVP or 1 mg epinephrine is recommended (class
      2B); patients with asystole or pulseless electrical activity should be
      resuscitated with epinephrine. AVP is not recommended for adult cardiac arrest
      patients with asystole or pulseless electrical activity; or pediatric cardiac
      arrest patients due to a lack of clinical data. Until definitive data about AVP
      vs. epinephrine effects during CPR are available, the present state of knowledge
      should be interpreted that two vasopressors are available for use instead of one.

PMID- 11993082
TI  - [Tracheobronchial injuries and fistulas].
AB  - This paper reviews the pathophysiological processes occurring after contact of
      blood with artificial surfaces during continuous haemofiltration and the
      predominant role of platelets in the genesis of extracorporeal thrombosis. A
      basic prerequisite for effective renal replacement therapy is adequate
      anticoagulation in order to inhibit activation of coagulation and to avoid
      haemofilter clotting. Antithrombotic regimens controlling plasma coagulation
      activation and platelet-surface interactions, as well as methods of coagulation
      monitoring are reviewed. In patients at risk for bleeding, combined
      antithrombotic regimens with short-acting antiaggregatory prostaglandins and
      unfractionated or fractionated heparin were more effective in reducing bleeding
      complications and morbidity during and after haemofiltration then heparinisation
      alone. Heparinoids and hirudine are indicated in patients with heparin-induced
      thrombocytopenia II. In patients at risk for thromboembolism, regional citrate
      anticoagulation may be beneficial. Performing continuous haemofiltration without
      antithrombotic therapy is not recommended.

PMID- 11993083
TI  - [Hemofiltration and blood coagulation].

PMID- 11993084
TI  - [Anesthesia for cesarean section].

PMID- 11993085
TI  - [Measures for reducing the use of blood transfusion].

PMID- 11993086
TI  - [Laparoscopic tumor nephrectomy].
AB  - Initially, laparoscopic surgery in urology was restricted to the treatment of
      benign diseases, whereas its role in the management of malignant disease was
      restricted to purely diagnostic procedures. Only recently has laparoscopy been
      introduced for the treatment of low stage renal cell carcinoma (RCC), and the
      data on both surgical efficiency and oncologic efficacy are very promising.
      Therefore, we present our experience with laparoscopic radical nephrectomy and
      data from literature. The technique of the transperitoneal approach is described
      in detail. Retroperitoneoscopy is a good alternative, however. Intact removal of
      the specimen within an organ bag to avoid tumor spillage is an important detail
      of our technique. Our experience amounts to radical nephrectomy in 121 patients.
      The indication was clinical stage T1-T2. Mean operative time and blood loss was
      2.4 h and 154 ml, respectively. The rate of minor or major complications was 5%
      and 4%, respectively. There was no conversion to open surgery in any patient.
      Mean postoperative hospital stay was 6.1 days. Data on tumor control are
      available for 73 patients with a mean follow-up of 13.3 months. There was no
      recurrence within this period. Radical nephrectomy for low-stage RCC is
      associated with low morbidity and great surgical efficiency. The rates for local
      recurrences and metastases are low, tumor-specific survival is high. However,
      there is still a lack of long-term data on large series of patients. Despite this
      fact, laparoscopy is already widely accepted for this indication, and it is quite
      likely that it will become the standard treatment.

PMID- 11993087
TI  - [Laparoscopic radical cystectomy with intracorporeal creation of a continent
      urinary diversion. Future or present?].
AB  - Once laparoscopic radical prostatectomy has been mastered, the step to performing
      a radical cystectomy is not that far. The challenge is to create the urinary
      diversion by laparoscopy. In this report we describe our experience with 11
      laparoscopic radical cystectomies and intracorporeal construction of a continent
      urinary diversion (Mainz pouch II) as a treatment option in patients with muscle
      invading bladder cancer. All 11 procedures could be performed successfully. A
      conversion to open surgery was not required in any case. The mean surgery time
      was 6.7 h. Except for two pouch fistulas we did not observe any intra- or
      postoperative complications. The functional as well as the oncological results
      are convincing. Less morbidity and faster recovery are the main advantages of
      this minimally invasive procedure. In addition, the low levels of blood loss,
      fluid shifts, and electrolyte loss considerably reduce cardiovascular stress.
      Radical cystectomy and construction of a continent urinary diversion represent
      the limit of technically feasible laparoscopy and should be done exclusively in
      specialized centers.

PMID- 11993088
TI  - [Port metastases: fact or fiction?].
AB  - In the early 1990s, the first reports appeared indicating a disturbingly high
      incidence (20%) of port site metastases following laparoscopic procedures for
      visceral and gynecological malignancies. At the same time, animal experiments
      were performed to investigate the phenomenon of port site metastases. The results
      were independently and repeatedly verified by different groups. In view of these
      distressing facts, a controversial, at times emotional discussion arose that
      evolved at least in part without strict regard to the available data. In the
      recent past, reports on increased incidence of port site metastases after
      laparoscopic interventions have completely vanished from the literature. Figures
      on incidence reported by various authors range between 0.5% and 1.3% and thus are
      comparable to the rate for surgical wound metastases (0.8-1.6%) as known from
      open conventional methods. Prospective studies have even shown that the survival
      rate in comparison to conventional techniques is 20% better, at least for
      laparoscopically treated stage I-III colorectal carcinomas. At present the
      discussion on the phenomenon of port site metastases can be considered closed.
      Port site metastases are thus no longer a fact, but also not fiction, since this
      phenomenon does occur in a small percentage of patients after laparoscopy just as
      after open surgery.

PMID- 11993089
TI  - [Results of comprehensive data collection concerning urologic laparoscopy].
AB  - To evaluate the current status of laparoscopy, the "Working Group Laparoscopy" of
      the German Urological Association performed a questionnaire among urologists in
      Germany. Of 300 questionnaires 183 were returned and analyzed (61%): 54% of the
      departments already performed laparoscopy and another 50% are planning to
      introduce this technique. The major concerns are economical (70%), long learning
      curve (92%), investment (53%), and lack of scientific data (76%). Simple
      nephrectomy, cryptorchism, and varicoceles are treated by 66, 59, and 58 of the
      96 departments laparoscopically (of 183 resp.). Laparoscopic surgery for radical
      prostatectomy and tumor nephrectomy is done by 32 and 34 of 96 departments. Only
      a minority of the centers performs more than 40 laparoscopies per year and
      indication. Compared to a survey conducted in 1995, the acceptance level of this
      technique has increased (100% vs 48%). Only a minority of the departments
      performs more than 40 laparoscopic interventions per year for one indication.

PMID- 11993090
TI  - [Urologic laparoscopy in marginal patients].
AB  - This paper describes the use of urological laparoscopy in borderline patients,
      focussing on geriatric patients and those with renal failure. Laparoscopy must
      not only be feasible but also at least as effective concerning operative and
      postoperative parameters when compared to standard open surgery. For laparoscopic
      nephrectomy most of these factors have tested positive. However, only a few
      papers have been published concerning borderline patients. In some cases the
      pneumoperitoneum may not be suitable for borderline patients and open operative
      techniques are preferred. Apart from this, the current literature supports the
      effectiveness of laparoscopy even when certain risk factors are present.
      Especially borderline patients can benefit from the laparoscopic approach for
      nephrectomy. Although data are scarce concerning other laparoscopic procedures in
      borderline patients, the results of laparoscopic nephrectomy should probably
      apply to other laparoscopic procedures.

PMID- 11993091
TI  - [Geometry of laparoscopy, telesurgery, training and telementoring].
AB  - Laparoscopic surgery in general is handicapped by the reduction of the range of
      motion from 6 to 4 degrees of freedom. This has a major impact on technically
      difficult procedures such as laparoscopic radical prostatectomy. Solutions for
      this problem include understanding the geometry of laparoscopy with sophisticated
      training programs, but also newly developed surgical robots, computer simulators,
      and telementoring. This article evaluates the value of these alternatives based
      on own experience and an analysis of the current literature. Our experience with
      robot-assisted surgery includes 244 laparoscopic radical prostatectomies using a
      voice-controlled camera arm (AESOP) and 6 telesurgical interventions with the da
      Vinci system. Additionally, experimental studies were performed focussing on the
      geometry of laparoscopy and new training concepts such as perfused pelvitrainers
      and computer simulation. Three-dimensional systems have not yet proved to be
      effective due to handling problems such as shutter glasses, video helmets, or
      reduced brightness. At present, there are only two robotic surgical systems
      (ZEUS, da Vinci) in clinical use for telesurgery, of which only the da Vinci
      provides stereovision and all 6 degrees of freedom (DOF). In the meantime, more
      than 100 laparoscopic radical prostatectomies have been performed with this
      system. However, there was no evidence of any advantages over the conventional
      laparoscopic approach. The ZEUS in combination with the telecommunication system
      SOKRATES is the only device that enables telemanipulation and telementoring over
      long distances (i.e., transatlantic). Robotic surgery represents a turning point
      in surgical research. However, broad use of robotic systems is limited mainly
      because of high investment and running costs. Whereas audiovisual telementoring
      will play a clear role in future training concepts, the need for telemanipulation
      or telesurgery has not yet been clarified.

PMID- 11993092
TI  - [Robot-assisted laparoscopy in urology. Radical prostatectomy and reconstructive
      retroperitoneal interventions].
AB  - Complex reconstructive laparoscopic procedures in the field of urology such as
      radical prostatectomy and pyeloplasty have attracted increased attention in the
      past 2 years. However, extensive laparoscopic experience is required to master
      these procedures. Therefore, it remains questionable whether these techniques,
      which have been shown to be of profit to the patient in the hands of a
      specialist, will achieve widespread distribution. We have employed computer
      technology to bridge the gap between open surgery and laparoscopic access and
      used the daVinci Surgical System to establish laparoscopic radical prostatectomy
      as well as pyeloplasty and other retroperitoneal procedures at our institution.
      With experience of more than 70 procedures, we find that with the assistance of
      the daVinci Surgical System both radical prostatectomy and retroperiteoneal
      procedures can be easily translated from open to minimally invasive procedures
      with a considerably shorter learning curve and without compromising patient
      safety. We expect that large incisions will be soon a thing of the past in
      urologic surgery. Computer technology, together with mechanical engineering, will
      play a major role in enabling us to achieve better results despite minimal
      invasiveness.

PMID- 11993093
TI  - [Minimally invasive therapy of obstruction of the kidney pelvis].
AB  - We report on 109 patients with ureteropelvic junction obstruction (UPJO) treated
      according to the following algorithm: intrinsic stenoses were treated by laser
      endopyelotomy (LEP). We used retroperitoneoscopy with ureterolysis to manage
      significant extrinsic UPJO due to a crossing vessel and either non-dismembered
      pyeloplasty in cases of an anterior vessel or dismembered pyeloplasty in cases of
      a posterior crossing vessel. Children were mostly treated by open dismembered
      pyeloplasty. Analysis of the factors that influence the postoperative results in
      the group of 64 patients treated by LEP showed significance for the presence of
      extrinsic causes of UPJO and the underlying grade of hydronephrosis. Based on our
      own results and the review of the literature, minimally invasive approaches for
      the management of UPJO have been proven safe and effective with results
      comparable to open surgery.

PMID- 11993094
TI  - [Postischemic reperfusion injury. Biochemical and methodological principles].
AB  - The term "ischemic reperfusion injury" encompasses all toxic events in a cell
      that occur during ischemia and subsequent reoxygenation. These reactions have a
      significant effect, for example, on the rate of organ survival in kidney
      transplantation. Reactive oxygen intermediates (ROI) play an important role in
      the process of postischemic reperfusion. The basic mechanisms of generation and
      detoxification of ROI as well as the possibilities for their registration and
      quantification under conditions of ischemic reperfusion injury in the rat kidney
      are demonstrated in this report. A prerequisite to developing cytoprotective
      strategies is understanding the precise course of these mechanisms to minimize
      damage caused by ischemia and the subsequent reperfusion, thus retaining the
      organ's function to the greatest extent.

PMID- 11993095
TI  - [Evaluation of the complementary drug Factor AF2 as a supportive agent in
      management of advanced urothelial carcinoma. Prospective randomized multicenter
      study].
AB  - This is a prospective randomized multicenter trial for evaluation of the
      biological response modifier Factor AF2 in advanced urothelial cancer treated
      with chemotherapy. Main aim of the study was the analysis of supportive effects.
      Additionally patients were examined with regard to tumor response, time to
      progression and survival. 106 patients with advanced urothelial cancer received
      chemotherapy with cisplatin and methotrexate. They were randomized for additional
      Factor AF2 (500 mg i.v., given at days 0-3, 7-10 and 11-14). Myelotoxicity was
      more common and severe in the group without Factor AF2 reaching statistical
      significance. Gastrointestinal side effects occurred in both groups, though grade
      III to IV toxicity was more common without Factor AF2. Overall remission rate was
      38%, median survival 33 weeks, mean time to progression 20 weeks. There was no
      significant difference between the two groups with or without Factor AF2.

PMID- 11993096
TI  - [Testing therapy optimization. Solution to the problem or mistake?].

PMID- 11993097
TI  - [Graduate education in Germany. Path out of the dead end].

PMID- 11993098
TI  - [From SKY, chips and proteomics. Molecular medicine in the time of high
      technology].

PMID- 11993099
TI  - [Urologic laparoscopy--where do we stand?].

PMID- 11993100
TI  - [Nurse's opinion on the applicability of the nursing process at the intensive
      care unit].
AB  - This paper aimed to identify the nurses opinion about the nursing process in the
      Intensive Care Unit (ICU), and the knowledge they had about this such assistance
      methodology. The method of investigation used had an qualitative approach, of the
      descriptive and exploratory kind, applying semi structured interviews to five
      nurses of ICU at a General Hospital of the south area of Rio Grande do Sul. It
      was verified that: the nurses interviewed had little knowledge about the subject,
      some referred using daily evolution and nursing prescription. Mostly, all
      recognize the importance of this assistance methodology, but consider essential
      that all the nursing staff should be trained and prepared to elaborate and
      execute it.

PMID- 11993101
TI  - [Pre-operative period of the heart surgical patient: nursing approach making a
      difference].
AB  - This is a study that was developed in a Cardiology Unit of a University Hospital
      in the country area of Rio Grande do Sul. Its aim was to identify the perception
      of the cardiac surgical patient about the pre-surgical orientations given by the
      nursing staff. The population was of male and female adult patients who were
      submitted to any cardiac surgical process. Semi-structured interviews were
      conducted to grasp the perception of the patient about the given information. The
      following themes emerged: tranquilizing awakening; stressful environment;
      nursing: being with and humanization; privileged feeling; technology in
      orientation; and orientation: meaning of clarifying, tranquility and courage.

PMID- 11993102
TI  - [The integration of psychiatry services in the general hospital].
AB  - This work consist of a bibliographic review about the inclusion of the psychiatry
      in general hospitals. Through it we were able to approach some historical aspects
      concerning the presence of mentally ill people in general hospitals, the creation
      and organization of psychiatric units in general hospitals, the hospitalization
      of psychiatric patients in institutions lacking specific units and the services
      of psychiatric interconsultation. The work consists of a part of a Master's
      dissertation in which we observed that there is a great amount of literature
      about the subject; however, all of them under the view of the nursing team. No
      references were found about the viewpoint of the mentally ill person about the
      hospitalization in a general hospital.

PMID- 11993103
TI  - [Analysis of expectations on the nurse's leadership in the light of Grid's
      theories].
AB  - Based on the understanding that leadership is a fundamental resource for nurses
      in health institutions, the aim of the authors was to analyze, under the light of
      Blake & Mouton's Grid Theories, the expectations of the Nursing team regarding
      nurse's leadership. The analysis was based on four investigations performed in
      different contexts of Brazilian Nursing and data were collected through the
      application of the "Grid & Leadership in Nursing Instrument" developed by
      Trevizan. Results show that the subjects prefer the Grid style 9.9. The authors
      discuss the results and emphasize the need for the development of leadership in
      Nursing.

PMID- 11993104
TI  - [The help relationship as work tool for psychiatric nurse: report of a case].
AB  - This study was carried out at a in-ward psychiatric hospital unit at the Medical
      School of Marilia and its aim was to discuss the applicability of the technique
      of help relation that occurred during the interaction of a nurse and a patient
      diagnosed as being schizophrenic. A patient presenting a diagnosis of schizo
      affective schizophrenia was selected and an interaction of about 35 minutes with
      him was developed. Afterwards, this moment was analyzed and discussed along with
      the teaching staff of the discipline "Interpersonal Relation Nurse/Patient". It
      was noted that even being a difficult approach to work with schizophrenic
      patients, it is possible to develop nursing care based on help relation.

PMID- 11993105
TI  - [Breast cancer: lonely encounter with fear to the unknown].
AB  - This is a qualitative research whose goal is to understand the experiences of
      women during the process of discovering breast cancer. The study involved eight
      college women who developed breast cancer, with ages ranging from 30 to 57 years.
      The comprehension of the studied phenomenon derived from Merleau-Ponty's (1996)
      phenomenology and to analyze the data it was used the five steps of Giorgi's
      (1985, 1997) phenomenological method, adding to them a sixth step proposed by
      Comiotto (1992). From this analysis, emerged two dimensions related to the
      essence Lonely encounter with the fear f the unknown: from the moment of finding
      the lump to the crucial moment of diagnosis, and experienced conflicts within the
      most significant relationships (husband, children and parents).

PMID- 11993106
TI  - [Consultation-action: a nursing action methodology in the field of occupational
      health].
AB  - The construction of this article reflects our attempt to demarcate knowledge as a
      bracket for the actions and interventions of nursing in the area of the worker's
      health. We believe that the proposals of the educative and caring actions in the
      field of the worker's health become appropriate and effective when engaged to the
      relation work-health-sickness, allowing the joint action nurse-worker in the
      inquiry, recognition and resolution of identified problems. So, the Consulta
      acao, by means of a method of joint action, rescues for nursing basic elements of
      the preventive intervention and the promotion of the worker's health.

PMID- 11993107
TI  - [The challenge of teaching how to deliver care from the perspective of the
      graduation nursing course student].
AB  - This paper refers to teaching/learning in a subject named Fundaments of Human
      Care III--Care Module--at the Nursing School of the Universidade Federal do Rio
      Grande do Sul, under the vision of the undergraduate student. In 1996, the
      subject started at the fourth semester of the curriculum, constituted of its
      basic thematic, and in which the students learn about the genesis of human care
      process. The daily reports of the students during this module practice at the
      Pediatric Oncology Unit (POU) of a University Hospital, in Porto Alegre, RS, were
      submitted to phenomenological analysis, based on Merleau-Ponty (Martins, 1992).
      From this analysis emerged the significance expressed by the student of the
      experiences on the POU; the relation between teaching-practice; theoretical basis
      and care.

PMID- 11993108
TI  - [Elements making up the identity of the nurse in descriptions expressed by
      graduating students].
AB  - Identity is usually conceived by choosing a series of characteristics which
      should be truly considered a person's own; it searches to fulfill needs that
      other way would stop individuals to build their own destinies. We aimed to
      apprehend the nurse's identity built by a group of Nursing undergraduate
      students. It was used a qualitative approach. "Care" was the word mostly used by
      the students while trying to explain what means to be a nurse. However, few of
      them could define the meaning of this care. From the students' speeches, we
      verified that the nurse is very related to the practical work, despite the fact
      that they affirm it to be an intellectual work. Another point discussed in this
      article is that the students do not mention the professors influence while
      building their perception of nurses.

PMID- 11993109
TI  - National Toxicology Program. Annual Plan. Fiscal year 2001.

PMID- 11993110
TI  - [Transporting models of reactive X-3B red dye in water-soil-crop continuums].
AB  - Reactive X-3B red dye entering into environment is a typical persistent organic
      pollutant(POPs). Transport of the dye from water to soil and from soil to crop
      compartment is a continuous ecological process. According to the cognitionm, the
      quantitative depiction of the process using mathematical models was theoretically
      discussed. Some of the mathematical models were also verified using burozem
      soybean, cinnamon soil-wheat, krasnozem-radish, aquorizem-rice systems. In
      particular, transference of the dye from water compartment to soil compartment by
      way of adsorbent mechanisms was accorded with the Langmuir model, and movement of
      the dye from soil compartment to crop compartment on the basis of root-absorbing
      mechanisms could be expressed using logarithmic crop-soil accumulation
      factor(CSAF) models.

PMID- 11993111
TI  - [Comparative study on ecotoxicological indexes of crops exposure to reactive X-3B
      red dye].
AB  - Ecotoxicological indexes of wheat, Chinese cabbage and rice exposed to reactive X
      3B red dye were studied using the experimental method of crop seed exposure. The
      results showed that reactions of the three crops to reactive X-3B red dye were
      different from each other. Based on the inhibition of seed gemination, the half
      effect concentration(IC50) of wheat, Chinese cabbage and rice was 8965, 7010 and
      7514 mg.L-1. Based on the inhibition of root elongation, the IC50 of wheat,
      Chinese cabbage and rice was 6534, 5882 and 4570 mg.L-1. When seedlings were
      cultured for seven days after the gemination of seeds and the remaining seeds or
      husks were discarded, fresh and dry growing biomass of the three crops exposed to
      the dye was both decreased with the increasing the concentration of reactive X-3B
      red dye. However, the decrease rate of fresh biomass was higher than that of dry
      biomass. Biomass index of wheat was most sensitive to reactive X-3B red dye,
      followed by rice, and Chinese cabbage was most inertia when the crops were
      exposed to reactive X-3B red dye with the high concentration of 4500 and 5000
      mg.L-1. As far as the tolerance of wheat, Chinese cabbage and rice to reactive X
      3B red dye was concerned, wheat had the strongest tolerance, on the contrary rice
      had the wakestone.

PMID- 11993112
TI  - [Effects of copper on rhizobia-Acacia auriculaeformis symbiotic association].
AB  - The effects of different levels of Cu2+ were studied individually on the growth
      of two Rhizobium strains and host plant growth, nodulation(%) and nitrogen
      fixation activity in A. auriculaeformis under solution culture conditions so as
      to explore a probability of utilization of the genus Acacia in revegetation of
      Cu(2+)-contaminated land. The results shows that Rhizobium sp. (Acacia
      auriculaeformis) had more stronger tolerance to Cu2+ iron than Rhizobium
      sp(Lespedeza formosa). The values of EC50 respectively achieved 0.129 mmol for
      Rhizobium sp. and 0.151 mmol for the N2-fixation activity. When the concentration
      of Cu2+ was over 0.50 mmol, N2-fixation activity had been inhabited thoroughly.
      Although the formation of nodules of Acacia auriculaeformis could continued, the
      growth of host plant had been inhibited with the appearance such as stunting,
      chlorosis. Between the noinodulating but adding nitrogen treat group and the
      inodulating without any nitrogen resource treat group, when Cu2+ < 0.125 mmol,
      the latter group showed better growth for A. auriculaeformis. There were higher
      contents of Cu in the underground tissues than in aboveground tissues.

PMID- 11993113
TI  - [Chlorobenze-stressing injury of the germination of soybean seed].
AB  - Effects of various doses of 1,2,4-trichlorobenze on seed germination and seedling
      growth of soybean were studied. The results indicated that 50-200 micrograms.g-1
      of 1,2,4-trichlorobenze had no effect on the percentage of seed germination, but
      delayed the rate of seedling growth. The seed germination was stopped by 300
      micrograms.g-1 of 1,2,4-trichlorobenze. The most activity of SOD took place on
      the 4th day after sowing of soybean seed in the normal condition, then tended to
      be in a certain level with a little alteration. Under the various dose stress of
      1,2,4-trichlorobenze, the activity of SOD in soybean hypocotyl was decreased,
      while MDA and protein contents as well as diameter of hypocotyls increased.
      Seedlings growth, fresh weight(FW), dry weight(DW) were inhibited, while the
      ratio of FW/DW didn't change. Damage-level of wheat seedlings was increased with
      increasing 1,2,4-trichlorobenze concentrations. Roots were more sensitive to
      1,2,4-trichlorobenze-stress than hypocotyls.

PMID- 11993114
TI  - [Accumulation and biodegradation of anthracene by Chlorella protothecoides under
      different trophic conditions].
AB  - The bioaccumulation and degradation of anthracene by the green alage(Chlorella
      prothecoides) under autotrophic and heterotrophic conditions were studied. About
      29% and 20% of anthracene(original concentration 1.0 mg.L-1) were degraded by
      light and by Chlorella protothecoides under the autotrophic condition,
      respectively. About 33.53% of anthracene (original concentration 2.5 mg.L-1) were
      degraded by C. protothecoides under the heterotrophic condition. The resistance
      and degradation ability of C. protothecoides under the heterotrophic condition
      was higher than that under the autotrophic conditions. More than 80% of residual
      anthracene was accumulated by algal cell under the two conditions. The
      bioaccumulation factor were 9064 and 1899, under the autotrophic and
      heterotropnic conditions, respectively. The net accumulation of anthracene,
      however, was much higher under the heterotropnic condition (202.29 micrograms)
      than that under the autotrophic condition (69.687 micrograms).

PMID- 11993115
TI  - [Effects of sulphur dioxide on the relationship between symbionts in lichen].
AB  - Xanthoparmellia mexicana was successfully isolating and culturing from its two
      symbionts and, preliminarily re-symbiosising its thalli in vitro performed from
      pure cultured photobiont and mycobiont. The solution exposure method was applied,
      confirming the toxic effect of sulfite solution with pH 4.0. The biochemical
      responses of lichen thalli and cultured symbionts to the short time stress of SO2
      were studied. The chlorophyll PQa value of photobiont was correlated with its
      absorption of SO2. Chlorophyll a was more sensitive than chlorophyll b;
      chlorophyll was damaged most severely by the exposure of 0.5 mg.L-1 of SO2
      fumigation, but was aggravated with the increase in the concentration of SO2 by
      way of solution exposure. The activity of acid phosphatase in lichen was mainly
      dependent on the photobiont. Reduced glutathione(GSH) was activated by oxidative
      stress of SO2. GSH was confirmed to be highly correlated with SO2 stress, and was
      proposed to be a significant and prospective biomarker of the status of lichen
      antioxidant system and the oxidative damage in lichen. The mycobiont was proposed
      to mainly resist the oxidative stress by SO2, while the photobiont was damaged
      more easily with energy depletion.

PMID- 11993116
TI  - [An experimental study for fixation of CO2 in stack gases using microalgae
      cultivation].
AB  - To obtain a microalgae growing well in the condition of stack gases and to find a
      good method of fixing greenhouse gases, the ZY-1 strain identified as a species
      of Chlorella genus was isolated from soil-water mixture samples collected from a
      paddy field after an enrichment culture using the reproduced stack gases
      containing 15% of CO2 and 2% of O2. The results showed that the range of CO2
      concentration for the optimum growth of the ZY-1 strain was 10-15%. The ZY-1
      strain had its maximum growth when the CO2 concentration was 10%. Under a broad
      range of physically conditions including 0.25-0.75 L.min-1 of air flowing rate,
      25-30 degrees C of temperature and pH 4-6, the ZY-1 strain had a steady growth.
      The optimum cultural condition with 0.397% of the CO2 utilization efficiency was
      seemed to be 10% of CO2, 25 degrees C and pH 5.0. It is feasible to fix
      greenhouse gases using the stack gases combined with the ZY-1 strain.

PMID- 11993117
TI  - [Artifical improvement of soil fertility in a regraded forest ecosystem by using
      municipal sewage sludge].
AB  - The increasing occurrence of forest ecosystem degradation is a serious problem in
      tropical and subtropical regions. Field experiments showed that the application
      of sludge from a sewage treatment plant could not only promote the growth and
      reproduction of trees, including the increase in the height and diameter of trees
      and thus being advantageous to the growth of shrub and herb of trees, but also
      improve soil fertility such as increasing soil organic matter and available
      nitrogen and phosphorus. The test of residual heavy metals of soil indicated that
      the application of sludge increased the content of Pb in the soil and the
      increment of Pb was varied with the increase of sludge usage. There was no
      significant increase in other heavy metals.

PMID- 11993118
TI  - [Effects of land utilization of sewage sludge on crops and soils].
AB  - Effects of land utilization of sewage sludge on crops and soil environment were
      studied using sewage sludge from the Northern Shenyang Plant of Wastewater
      Treatment. The results showed that contents of nitrogen, phosphorus and organic
      matter in the soil were increased after the utilization of sewage sludge, thus
      being advantageous to growth and development of crops. The biomass of rice after
      having applied 22.5 and 45 t.hm-2 of sewage sludge was increased by 11.48%-11.83%
      compared with the control. There was no evident harmful effect of heavy methals
      from sewage sludge on quality of soil environment, agricultural products and
      underground water when the application of sewage sludge was controlled within the
      range of 45 t.hm-2.

PMID- 11993119
TI  - [Remediation of chromium-polluted soil using municipal solid waste compost].
AB  - A study on the feasibiltiy of remediation of Cr-polluted soil using municipal
      solid waste(MSW) compost was carried out. The result showed that organic
      matter(O.M.), Eh, pH and < 0.01 mm of clay would influence the bioavailability of
      chromium in the soil, and O. M. and Eh were the principal influencing factors in
      the dryfield and inundating soil, up to 73.40% and 55.5% of the contribution rate
      affecting the bioavailability of chromium, respectively. The osmosis of the soil
      was improved when compost was applied, but the quantity of movable chromium was
      reduced because chromium in soil was deoxidized and adsorbed. MSW compost could
      reduce the absorption of chromium by the tested plant. The yield of the plant
      grown in the dry soil was increased by 35.9% and the content of Cr in the plant
      was decreased by 48.9%. The effect was more notable in the inundating soil: 86.3%
      of the yield increased and 23.8% of the Cr content decreased. However, MSW
      compost could not increase the risk of other heavy metal pollution.

PMID- 11993120
TI  - [Distribution and degradation of SAS in soil environments in the Taihu Lake
      region].
AB  - Soil samples of different soil types under different land use patterns and
      environmental impacts were collected in Wuxian City in the Taihu Lake region. The
      contents of SAS were determined by Azure A colorimeter. Degradation of LAS was
      studied in the water and soil mediums by using laboratory incubation. The SAS
      concentration in the studied soils ranged from 2 to 10 mg.kg-1, varied with soil
      conditions. Profile distribution of SAS showed decreasing trend down to the soil
      bottom, where 0.7 mg.kg-1 of SAS was still detected. The degradation of LAS in
      three dominant types of paddy soils obeyed the primary reaction equation like
      that of soil organic matter with the half residence time in range of 9-16 days.
      The data indicates the relative accumulation of SAS in the soils in the Taihu
      Lake region and longer residence of such synthetic organic compounds in the soil
      environments.

PMID- 11993121
TI  - [Distribution characteristics and chemical pattern of cadmium in grasses planted
      in the cadmium contaminated soil].
AB  - In this paper, the distribution and chemical pattern of Cd in the grasses planted
      in Cd contaminated soil in western suburb of Shenyang were analyzed. The results
      showed that Cd was mainly distributed in the grass roots, and characteristics of
      Cd distribution in various grasses were different. Some grasses had resisting
      ability against Cd, some had strong capability of bio-accumulation for Cd.
      Results of different grasses extracted by different solvents showed that acid
      soluble Cd in grasses was about 63.3% of total, and water-soluble and organic Cd
      were little, accounting for 0.7% and 0.4% of total respectively. Acid-soluble Cd
      was more active than the others during the transformation in the soil-plant
      system, while water-soluble Cd had certain regularity with the change of time and
      temperature, and organic Cd became more active with the increase of solvent
      polarity.

PMID- 11993122
TI  - [Effects of Cu and As on germination and seedling growth of crops].
AB  - A solution-culture experiment was carried out to explore effects of Cu and As on
      the germination and seedling growth of crops. The results showed that Cu or As
      pollution could reduce the activities of protease and diastase, inhibit the
      seedling growth and the respiration rate of germinating seed of soybean. The
      inhibition was strengthened with the increase in the concentrations of Cu and As.
      However, the activity of POD was increased with the concentrations of Cu and As
      in the exposed solution.

PMID- 11993123
TI  - [Cadmium adsorption in soil influenced by dissolved organic matter derived from
      rice straw and sediment].
AB  - Dissolved organic matter (DOM) is an active component in territorial ecosystems.
      Effects of two types of DOMs extracted from sediment(DOMsed) and rice
      straw(DOMrs) on isotherm adsorption of Cd in latosol red soil (acidic soil),
      paddy soil and drab soil(alkaline soil) were studied using batch equilibrium
      studies. The maximum adsorption of Cd in all the 3 soils used was reduced by the
      additions of both of DOMsed and DOMrs. The range of the maximum adsorption of Cd
      decreased from 17.3% to 93.9% from all the 3 soils when DOMs were added. It was
      found that the decreased in the maximum adsorption of Cd was in order of latosol
      red soil > paddy soil > drab soil when the same DOM(DOMsed or DOMrs) was added.
      Effects of DOMsed or DOMrs on Cd adsorption were positively related with the soil
      pH. The maximum adsorption of Cd in the soils was dependent on the
      characteristics of soil solid when no DOM was added, and decided by the DOMs in
      soil solution when DOM was added. The results imply that the proposed technology
      using organic manure to stabilize Cd in soils is not suitable for remediation of
      contaminated soil.

PMID- 11993124
TI  - [Acute toxicological effects of heavy metal pollution in soils on earthworms].
AB  - Acute and sub-acute lethal effects of single and combined Cu, Zn, Pb and Cd on
      earthworm was determined using meadow brown soil. Results indicated that the
      mortality of earthworm was significantly related with the concentrations of Cu
      and Zn in the soil (alpha = 0.05, RCu = 0.86, RPb = 0.87), and the inhibition
      rate of earthworm growth was significantly related with the concentration of Cu
      in the soil (alpha = 0.05, RCu = 0.84). There was no significant relation between
      the concentrations of other heavy metals tested and the death rate and the growth
      inhibition rate. The degree of individual earthworm enduring the toxicity of
      heavy metals varied greatly. The threshold concentration of toxicity defined by
      statistical method, the level to conduce the death of individual earthworm was
      300 mg.kg-1 for Cu, 1300 mg.kg-1 for Zn, 1700 mg.kg-1 for Pb, 300 mg.kg-1 for Cd.
      LC50 was 400-450 mg.kg-1 for Cu, 1500-1900 mg.kg-1 for Zn, 2350-2400 mg.kg-1 for
      Pb and 900 mg.kg-1 for Cd. Combined effects of single Cu, Zn, Pb and Cd to
      conduce more than 10% of the death rate of earthworm could result in 100% of the
      death rate of earthworm, thus showing the strong synergistic joint effect of the
      heavy metals.

PMID- 11993125
TI  - [Effects of mercury and cadmium on the activity of urease in soils. I. Urea
      concentration].
AB  - Relationship between urease activity and heavy metals(Hg and Cd) under the
      condition of different urea concentration was studied. The results showed that
      the added urea concentration had an obvious positive effect on urease activity.
      Line and Langmuir models could be well described the relationship within the urea
      concentration tested. The calculation of urease parameters such as urea percent,
      urea-varying percent, and the maximum superficial urease activity reflected that
      Hg and Cd could remarkably reduce the positive effect from added urea, combined
      pollution of Hg + Cd displayed the most inhibition of the positive effect, and Hg
      produced the most ecological toxicity acting on soil urease activity. There was
      an adsorption mechanism in the enzyme reaction.

PMID- 11993126
TI  - [Comprehensive treatment of aquariculture water pollution by flocculant and
      complex strain].
AB  - In order to purify aquariculture water, decrease fish-disease and sewage
      discharge, the purification efficiency of several types of flocculants such as
      PFS, PDMDAAC, EM, and combining PFS-PDMDAAC, PFS-PDMDAAC-EM used for treatment of
      soft-shelled turlle pond water were studied, and optimal mathematical of water
      qualities effected by several types of purification method were established. The
      results showed that the comprehensive treatment had the best purifcation
      efficiency, the flocculation rate was above 98%, CODcr removed rate was above
      95%, BOD5/CODcr of pond water and effluent decreased from 0.61 and 0.51 to 0.24
      and 0.29 respectively, the biodegradable matter in waters have been effectively
      removed, when 30 mg.L-1 PFS, 0.5 mg.L-1 PDMDAAC and 30 ml.m-3 EM were added. The
      various major water qualities were keeded stabilization and had attained special
      aquariculture water quality standard. The water qualities of pond water and that
      of effluent were showed no difference, which had attained pollution-free
      discharge and ecological equilibrium aquariculture.

PMID- 11993127
TI  - [Health-quality problems of paddy soil in the Taihu region].
AB  - The concept of soil health quality was discussed from the angle of sustainable
      and safe agricultural production and nutritive agricultural products. Based on
      the data of 13 higher-yield rice-farms and its corresponding irrigated rivers in
      the Taihu region, problems of health quality occurred in paddy soil were
      discussed. Owing to the high application of inorganic fertilizers in those farms,
      high available P and N were observed in paddy soil and river sediments. The
      contents of heavy metals such as Pb, Cu, Ni and Co in paddy soil were still at
      the level of background values. However, it was found that some rivers were
      seriously polluted by Cu, Zn and Pb. Several cases of point-source pollution of
      heavy metal were found in paddy soil in the region. The contents of DDT and HCH
      in soils and river sediments were lower than their maximum allowable
      concentrations. The results of lower selenium content in agricultural product
      owing to lower content in paddy soil indicted that the Taihu region is a selenium
      deficient area.

PMID- 11993128
TI  - [Coupling relationship between water and salt of waters ecosystems in arid zone:
      a case study in Xinjiang Tarim River basin].
AB  - The pollution of waters ecosystems is caused by natural and artificial factors in
      Tarim River. Temporal and spatial variation of surface runoff is the main reason
      for changes of coupling relationship between water and salt. In the end of 1950s,
      mineralization degree was less than 1.0 g.L-1 from the upper reaches to the lower
      reaches of Tetema Lake in Tarim River. At present, only in July, August and
      October, mineralization degree is less than 1.0 g.L-1. During the other months,
      mineralization degree is more than 3.0 g.L-1 in Alaer Lake. In Qiala (the lower
      reaches of Tarim River), mineralization degree is more than 1.0 g.L-1 except in
      March. Moreover, mineralization degree is about 5.0 g.L-1 in July and December.
      It is showed that annual water quality belongs to the fifth seriously polluted
      water in Alaer, Xinquman and Yingbazha. Meanwhile, annual water quality in Qiala
      belongs to the fourth polluted water. In a word, water quality state and
      hydrological chemistry component are the most obviously indicator for coupling
      relationship between water and salt in Tarim River.

PMID- 11993129
TI  - [Bioindication of organochlorine pesticides by night heron in Taihu wetland
      ecosystem].
AB  - Based on field ecological investigation on the colony of herons in Yuantouzhu of
      Taihu in 1999, the regurgitated foods by chicks of night heron were collected for
      prey type identification and chemical analysis. Besides, eggs of night heron, and
      sediments and waters in foraging habitats were sampled for chemical analysis as
      well. alpha-HCH, beta-HCH, gamma-HCH, Aldrin, Dieldrin, Endrin, Heptachlor,
      Heptachlor epoxide, p,p'-DDE, p,p'-DDD, o,p'-DDT and p,p'-DDT were determined in
      laboratory by gas chromatography. The results indicated that HCH isomers, DDT and
      its metabolites could be detected in various environments and preys of night
      heron, although the organochlorined chemicals were banned for almost 20 years.
      Moreover, The results showed that eggs of night heron could accumulate
      organochlorine pesticides by as much as a factor of 10(3)-10(4), which can make
      chemical analysis much easier. So they are good bio-indicators for organochlorine
      contamination level in wetland environments.

PMID- 11993130
TI  - [Residue and distribution of heavy metals in tissues of night heron chick bred in
      Yuantouzhu, Wuxi].
AB  - This study analyzed Cd, Pb, Cr, Hg and Se in organs and tissues of night heron
      chick bred in Yuantouzhu, Taihu lake. Cr and Se have higher residue level in all
      the samples, compared to the residue of Cd, Pb and Cd mainly concentrated in
      feathers, on the other hand, Se, Hg and Cr were accumulated in livers. The
      results proofed that feather and liver were the object organs for accumulation of
      heavy metals. The data showed that Hg and Cd have some relationship with Se in
      birds. Compared with other studies, residue levels of heavy metals in night heron
      in Wuxi were not harmful.

PMID- 11993131
TI  - [Evaluating ground water vulnerability in West Lake Watershed by using DRASTIC
      model].
AB  - Supported by Blackland GRASS Geographic Information System (GIS), the basic and
      special environmental databases of West Lake Watershed were established. The
      vulnerability map of ground water pollution was calculated and drawn by
      integrating GIS and DRASTIC model. Comparing to the present situation of land
      use, critical area of ground water pollution had been determined. The residential
      area accounted for 14.7% of the high susceptible area, and wastewater in the
      residential area should be piped and treated first.

PMID- 11993132
TI  - [Retrospect and prospect of pollution ecology].
AB  - Since 1970s, pollution ecology has gone through several historical stages
      including the natal, growing and developing and expanding stage with the rise in
      environmental sciences and the development of applied ecology. The theoretical
      system and researching methods with special characteristic of the subject has
      taken shape. So far pollution ecology has become an independent discipline to
      probe into interactions between biological systems and polluted environment and
      to control and remedy polluted environment using ecological principles, is an
      important component part of applied ecology and derives from amalgamation and
      intersection between ecology is faced with challenges and opportunities. A
      breakthrough and good progresses will be made in its branches and frontal fields
      such as ecology of combined pollution, contaminant ecotoxicology, ecological
      processes of pollutants and ecological remediation of contaminated environment.

PMID- 11993133
TI  - [Constructed wetland and its application for industrial wastewater treatment].
AB  - This paper presents a review of the mechanisms and advantages of the constructed
      wetland (CW). The wetland as land-intensive biological treatment systems has
      complicated purificative mechanisms, including physio-chemistry such as substrate
      adsorption, substrate filtration, plant adsorption, pollutant sediment ion
      exchange and biochemistry such as plant sorption, microbiology oxidation,
      microbiology ammunition. Besides the aesthetic aspect of macrophytes to provide
      wildlife habitats, the advantages of CW are relatively low cost, simple operation
      with stable effluent quality and good resistance to shock loading. In recent
      years, these systems have been used in the purification of domestic sewage.
      Nowadays attention has focused particularly on the use of constructed wetlands
      for the treatment of industrial effluents. According to the study and present
      state of constructed wetland for industrial wastewater treatment, feasibility of
      CW for special industrial wastewater treatment and investigations in the future
      were discussed.

PMID- 11993134
TI  - [Nonpoint pollution control for rural areas of China with ecological engineering
      technologies].
AB  - Nonpoint pollution from rural areas is the results of the ecosystem degradation,
      and ecological engineering technologies are good ways for the restoration of
      watershed and enhancing material cycling. There are two types of treatment
      strategies: to control the polluted runoff and to reduce the pollutants from the
      sources. Six control technologies are introduced and they are multipond systems,
      grassed filter trips, wetland systems, eco-agriculture, slope ecological
      engineering, ecological treatment of wastewater and solid waste. These
      technologies need to be combined systematically in order to form a watershed
      ecological engineering. In the control program, it is important to use
      countermeasure suitable to the local conditions. In addition, the input of
      sufficient investment, management and education is necessary.

PMID- 11993135
TI  - [Advances in studies on accumulation and leaching of nitrate in farming soil].
AB  - Nitrate leaching in farming soil is the main reason resulting in ground water
      pollution of nitrate. The main factors, which can affect nitrate accumulation and
      leaching greatly, include fertilization, precipitation, irrigation, soil
      characteristics, and cultivation system. Superfluous nitrogen in soil caused
      either by using chemical fertilizer and manure solely or compost will result in
      nitrate accumulation. Cultivation and plow systems also can affect the process of
      nitrate accumulating and leaching. Down flows due to irrigation or precipitation
      are the necessary condition and carrier for transference and leaching of
      accumulated nitrate in soil. Great pores are the main channels for down flows.
      These factors always work corporately. Mathematical model, which has been
      developed quickly and used widely, may be a good method to study and predict
      nitrate leaching in farming land.

PMID- 11993136
TI  - [Interaction between microorganisms and heavy metals and its application].
AB  - Interactions between microorganisms and heavy metals were expatriated in many
      ways. Because of their resistance and detoxification to heavy metals,
      microorganisms are able to leach, absorb and transform heavy metals, which has
      been actively applied to extract heavy metals from low-rate ore in mine
      exploitation. Although heavy metals are toxic to microorganisms population and
      harmful to its processes, some special microorganisms have been applied to the
      treatment of industrial waste materials and the remediation of soils polluted by
      heavy metals. The application of microbiological biomass and activity to
      evaluating the pollution situation and ecological risk of heavy metals in
      environment media is also significant.

PMID- 11993137
TI  - [Bioremediation of low-level radionuclide contaminated soils and water].
AB  - Different anthroponic factors have led up to increasing background concentrations
      of radionuclides in human ecosystems. As long as these radionuclides enter into
      soil-water substrates, they can pose hazards to human health through different
      pathways. Since most conventional chemical or physical procedures are not
      practical for dealing with low-level radionuclides in the water-soil substrates,
      new remediation technologies are being developed to tackle the problem.
      Bioremediation has attracted much attention because of its many advantages such
      as low cost and less environmental disturbance. The present paper summarizes the
      sources of radionuclides and introduces the concept of low-level radionuclide
      bioremediation. The state of the art in the field of bioremediation of low-level
      radionuclide contaminated water-soil substrates has also been reviewed and
      summarized in this paper. On the basis of above mentioned discussions the future
      developing trends were put forward.

PMID- 11993138
TI  - [Molecular-ecological technology of microorganisms and its application to
      research on environmental pollution].
AB  - Nucleicacid probe detection, PCR technique using primer, DNA sequential analysis,
      and electrophoresis separation and display were summarized and the application of
      these techniques to research on environmental pollution and future developing
      directions were discussed. It was pointed out that molecular-ecological
      technology of microorganisms are playing an important role in studying on
      relationships between microorganisms and contaminated environment. There are some
      important advances such as genetic adaptation and evolutionary mechanisms of
      microorganisms in contaminated environment, the positioning of pollutant
      degrading genes of microorganisms and the construction of microbiological
      engineering bacteria, thus promoting the development of molecular ecology for
      bioremediation of contaminated environment.

PMID- 11993139
TI  - [Utilization of embryo development technique of Brachydanio rerio to evaluating
      toxicity on various chemicals].
AB  - The application of Brachydanio rerio embryo development technique to research on
      environmental science was summarized in this paper. This testing technique was
      approved as one of standard methods for chemical toxicity test, especially for
      teratogensis, by international organizations (OECD, DIN). There are many
      advantages of this testing, e.g., low cost, easy operation, high sensitivity and
      multiple sensible endpoints, comparing with other toxicity testing. Also, it was
      used to judge toxic mechanism of chemicals. The embryo development of zebrafish
      can be affected obviously by heavy metal, pesticide, organic reagent and complex
      chemicals. Among them, Cu and Hg appeared stronger toxicity, and Cr was weaker
      for heavy metals. TPTA and Lindane were higher toxicity within pesticide, and
      they were higher toxicity if the organic reagent with one or more halogen
      substituent(s) and aminobenzene. These results were correspondent with other
      toxicity testing, and it showed higher sensitivity, especially a sublethal
      endpoint was selected. Therefore, it can be expected to test toxicity and
      teratogensis on mixed pollutant monitoring.

PMID- 11993140
TI  - [Study on the effects of disposing of pig manure with EM and OL].
AB  - The effects of EM and OL on the color, pH value, stink and the various kinds of
      harmful microbes of pig manure were analyzed. The results show that EM and OL
      could significantly reduce the stink and restrain the number of harmful microbes.
      At the same time, the rotting process of pig manure was accelerated, and the
      number of flies around pig manure reduced.

PMID- 11993141
TI  - Presurgical implant-supported prostheses: an experimental technique for immediate
      loading. Interview by Arun K. Garg.

PMID- 11993142
TI  - Heat-activated solderless passivation--the alternative to soldering. Interview by
      Arun K. Garg.

PMID- 11993143
TI  - [Intergenerational exchanges].

PMID- 11993144
TI  - [Value and limits of intergenerational exchanges].

PMID- 11993145
TI  - [AGIRabcd, an association for creating intergenerational exchanges].

PMID- 11993146
TI  - ["Picnic", a loony tale for all ages].

PMID- 11993147
TI  - [Why not a day care center in a nursing home?].

PMID- 11993148
TI  - [Intergenerational health promotion project in nursing homes].

PMID- 11993149
TI  - [Intergenerational relations in a geriatric hospital].

PMID- 11993150
TI  - [Dietetics. Chocolate and its benefits].

PMID- 11993151
TI  - [Scabies, a pathology still present in the elderly].

PMID- 11993152
TI  - [Therapeutic health promotion and therapy facilitated by animals].

PMID- 11993153
TI  - [The philosophy of Zootherapy Quebec].

PMID- 11993155
TI  - [Current topics in prion diseases].

PMID- 11993156
TI  - [Diffusion tensor analysis: principles and applications].
AB  - Diffusion tensor analysis represents a versatile yet powerful application of
      magnetic resonance imaging (MRI). Early applications of diffusion weighted
      imaging(DWI), especially those related to ischemic brain disease were quickly
      overshadowed by more advanced applications of DTA, namely, those dealing with
      anisotropy analysis. Considering the array of possibilities, from neuronal tract
      tracing to neuronal density imaging, DTA is rapidly becoming an indispensable
      tool not only in neuroscience but also in clinical investigations of the brain.

PMID- 11993157
TI  - [Horizontal canal benign paroxysmal positional vertigo: the dynamism of
      otoliths].

PMID- 11993158
TI  - [Longitudinal study of procedural memory in patients with Alzheimer-type
      dementia].
AB  - We never forget how to ride a bicycle, and it is thought that procedural memories
      are retained for a long time. Recently, it was reported that patients with
      dementia of the Alzheimer type(DAT) could not only acquire, but also retain, long
      lasting procedural memories. Previous group studies had shown procedural memory
      retention times of only 1 month in DAT patients, while amnesic patients and
      healthy people could retain such memories for 12 months. The relationship between
      the ability to retain procedural memory and the stage of the disease is not
      clear, as to date there has been no longitudinal study of procedural memory
      retention in DAT patients. Thus, we examined DAT patients' ability to retain long
      term procedural memories (after 1, 5 and 20 months), and analyzed the
      relationship between procedural memory ability and the progress of disease. Motor
      type procedural memory was examined using the mirror tracing task and the bi
      manual coordinated tracing task. All three of the DAT patients showed improvement
      in their performance. The time required for the tracing was reduced between
      trials, and the improvement did not disappear between sessions, or rather, their
      times further decreased in subsequent sessions. Even the most severe DAT patient
      (Mini Mental State Examination(MMSE) score of 4) was able to acquire the
      procedural memory and retain it for at least 3 months. Furthermore, one of the
      subjects showed retention of the procedural memory at 20 months. Our results
      suggest that DAT patients can retain procedural memories for extended periods,
      with no relationship between retention ability and disease progression. It is
      possible for even severely demented patients to acquire and retain motor-type
      procedural memories. Cognitive rehabilitation in DAT appears to be effective, and
      it is possible for DAT patients to learn new things. It may be that DAT patients
      can ameliorate their quality of life by using retained procedural memory.

PMID- 11993159
TI  - [Pathophysiology of medial temporal lobe epilepsy: role of cerebral dysgenesis].
AB  - We studied the incidence of cerebral dysgenetic lesions(CD) in 39 operated
      patients with medial temporal lobe epilepsy(MTLE) who had hippocampal sclerosis.
      Four patients had CD, such as menigocele at the ipsilateral temporal fossa,
      schizencephaly in the ipsilateral peri-Rolandic area, focal cortical dysplasia in
      the ipsilateral inferior temporal gyrus and periventricular nodular heterotopia
      at the bilateral inferior horns of the lateral ventricle. Histological
      examinations of the resected lateral temporal lobes from 29 MTLE patients
      revealed the presence of microdysgenesis (microscopic cerebral dysgenesis) in 28
      patients, including heterotopic white matter neuron(24 cases), molecular layer
      neuron(14), oligodendroglial cell cluster(11), dilated perivascular space(10).
      These findings suggest that the congenital factors, as well as hippocampal
      sclerosis, may be involved in the development of MTLE.

PMID- 11993160
TI  - [Horizontal canal benign paroxysmal positional vertigo (HC-BPPV) with direction
      changing apogeotropic nystagmus: a case with the more-triggering side altering
      over a short-term].
AB  - We report a 44-year-old man who had apogeotropic nystagmus with the rotation of
      his head to either side from the supine position. His nystagmus lasted more than
      2 minutes and was difficult to treat with. There were no neurological
      abnormalities except for the nystagmus and no findings suggesting intracranial
      disease on MRI. The head-position in which more intense nystagmus was evoked
      changed again and again in a short term. We diagnosed his illness as
      cupulolithiasis of horizontal canal, however, the affected ear could not be
      explained by any of the previously supposed mechanisms. In our case, we speculate
      the following mechanism. Otoliths were located on the right utricular side of the
      cupula. All of them were attached on the cupula at the beginning(attached phase)
      and then, some of them were detached from it(detached phase). The extent of the
      cupular deviation differed in each phase when the otoliths were beneath the
      cupula with his head turned to the left lateral position. According to Ewald's
      second law, more intense nystagmus is evoked when the cupula deviates toward the
      utricle than away from it. The patient's head-position in which more intense
      nystagmus was evoked changed according to the balance between the effect of
      Ewald's second law and the amount of otoliths detached from cupula. Our case
      showed that, in HC-BPPV with direction-changing apogeotropic nystagmus, we could
      not be certain about which ear was diseased. Therefore, it may be difficult to
      apply exercise therapy by determining the affected ear based on the head-position
      in which more intense nystagmus is evoked.

PMID- 11993161
TI  - [Speech-related tremor of lips: a focal task-specific tremor].
AB  - We report a 66-year-old Japanese woman in whom tremor of lips appeared during
      speech. Her past and family histories were unremarkable. On neurological
      examination, there was no abnormal finding except the lip tremor. Results of
      laboratory findings were all within normal levels. Her MRI and EEG were normal.
      Surface EMG studies revealed that regular grouped discharges at a frequency of
      about 4-5 Hz appeared in the orbicularis oris muscle only during voluntary
      speaking. The tremor was not observed under conditions of a purposeless phonation
      or a vocalization of a simple word, suggesting that the tremor was not a vocal
      tremor but a task-specific tremor related to speaking. Administration of a beta
      blocker and consumption of small amount of alcohol could effectively improve the
      tremor, possibly suggesting that this type of tremor might be a clinical variant
      of essential tremor.

PMID- 11993162
TI  - [A case of crossed aphasia in a dextral patient with polycythemia].
AB  - We report a 72-year-old right-handed man who was diagnosed as having crossed
      aphasia. He had polycythemia, hypertension and an old cerebral infarction in the
      right occipital lobe. He was admitted to our hospital because of muscle weakness
      in the left extremities at the age of 71. In the laboratory data, red blood
      cells(689 x 10(4)/microliter) and platelets(87.6 x 10(4)/microliter) were
      increased in number. Brain CT detected a right putaminal hematoma and an old
      infarct in the occipital lobe on the right. After admission, he developed non
      fluent speech, and impairments of auditory comprehension, writing and naming due
      to the infarction in his right cerebral hemisphere including the middle cerebral
      artery distribution. The standard language test of aphasia(SLTA) revealed marked
      impairments in the language function, except for reading kana and kanji words.
      This writing was severely impaired compared with other language dysfunctions.
      Auditory comprehension, repetition and reading were impaired at the sentence
      level rather than at the kana word level. Furthermore, he suffered from left
      hemiparesis and left unilateral spatial neglect. We diagnosed his impairments of
      language function as crossed aphasia based on his right-handedness, CT findings
      and the results of SLTA. His language center was considered to be located in both
      cerebral hemispheres. Compared with typical findings in reported cases of crossed
      aphasia, the presence of both non-fluent speech and mutism were consistent with
      previous observations. However, the marked impairments of auditory comprehension,
      repetition and naming were different. Polycythemia and hypertension were
      considered to be the risk factors of cerebral infarction in our patient.

PMID- 11993163
TI  - [A case of spinal sarcoidosis complaining of chest and back pain as a first
      manifestation and mimicking syringomyelia on MRI].
AB  - The patient was a 24-year-old female complaining of bell-shaped chest and back
      pain with visual disturbance. Chest X-ray showed bilateral hilar lymphadenopathy
      without the presence of pleural effusion. Bronchoalveolar fluid showed
      lymphocytosis with an elevated CD 4/CD 8 ratio. Transbronchial lung biopsy
      demonstrated a non-caserous granulomatous lesion with an accumulation of
      epitheloid cells, suggesting lung sarcoidosis. No abnormality of
      electrocardiogram was detectable, and spinal tap for examination of chest and
      back pain demonstrated on elevated level of beta 2-microglobulin, and a normal
      angiotensin converting enzyme level. Spinal MRI showed a lineal lesion mimicking
      syringomyelia on T 2-weighted image. Steroid administration was started for the
      chest and back pain, since the spinal lesion was suspected due to spinal
      sarcoidosis. All clinical and laboratory findings, without the presence of
      pleural effusion or cardiac fluid, supported the diagnosis of spinal sarcoidosis
      causing chest and back pain. In the literature, patients with spinal sarcoidosis
      manifesting chest and back pain and with a MRI finding mimicking syringomyelia
      have been rarely reported. This case might be important in considering spinal
      cord sarcoidosis as a differential diagnosis of chest and back pain.

PMID- 11993164
TI  - [A case of medial medullary infarction with persistent primitive hypoglossal
      artery].
AB  - A 66-year-old woman was admitted to our hospital because of vomiting, dizziness
      and vertigo. Neurological examination on admission revealed only upbeat nystagmus
      without cranial nerve symptoms, paresis, cerebellar signs or sensory
      disturbances. Magnetic resonance(MR) images demonstrated a new T 2 high intensity
      and T 1 iso-intensity signal lesion in the right upper medial medulla. This
      medial medullary infarction caused central vestibular dysfunction. MR angiography
      and digital subtraction angiography demonstrated a persistent primitive
      hypoglossal artery (PPHA) originating from the right internal carotid artery to
      the vertebrobasilar artery associated with the stenosis of the right internal
      carotid artery at the level of the cervical bifurcation. This is the first report
      of medullary infarction with persistent carotid-basilar anastomosis. We suspected
      this medullary infarction was caused by artery to artery embolism in the branch
      of the right vertebral artery through the PPHA distal originated from the
      stenosis of the right internal carotid artery.

PMID- 11993165
TI  - [Chondroma of the lumbar spinal canal: a case report].
AB  - Chondroma is a benign cartilaginous tumor and fairly rare in the spine. A case of
      chondroma in the lumbar spine is presented. A male at age 66 was suffered from
      progressive low back pain associated with hypesthesia in his right leg.
      Radiographic examination showed an extradural mass in the dorsal part of spinal
      canal at L 5 level. No osteolytic change was noted by CT scan. MRI showed iso
      intensity with marginal enhancement on T 1-weighted images and heterogeneous
      intensity on T 2-weighted image. The mass was totally removed by laminectomy and
      pathohistologically diagnosed as chondroma. Postoperative course was uneventful
      and the symptoms disappeared completely. One of the origin of chondroma is
      thought to be metaplasia of the connective tissue in contact with spine. This is
      why no pathological change was found in bone adjacent to the tumor. Careful
      preoperative diagnosis and total removal of the tumor is important since
      malignant transformation may happen in chondroma.

PMID- 11993166
TI  - [A case of microcystic meningioma with characteristic findings on neuroimaging].

PMID- 11993167
TI  - [An adult case of acute necrotizing encephalopathy].

PMID- 11993168
TI  - [Severe necrotic lesion of the cerebellar white matter observed in a patient
      presenting subacute cerebellar and brain stem dysfunction associated with
      positive serum anti-SS-A and SS-B antibodies].

PMID- 11993169
TI  - [Battered child syndrome and head trauma in infants].

PMID- 11993170
TI  - [Cranioplasty using autogenous bone cryopreserved with dimethylsulfoxide (DMSO)].
AB  - It is generally agreed that the autogenous bone flap which has been removed at
      the time of external decompression would be superior to any artificial material
      if it can be used in cranioplasty. Cranioplasty using autogenous frozen bone
      graft has been reported and showed good results except for infection and severe
      bone absorption. We conducted 39 cases of cranioplasty with cryopreserved
      autogenous bone in the presence of 10% of Dimethylsulfoxide (DMSO), which has
      been reported as a cryoprotective agent. Although no remarkable histological
      effects have been recognized in frozen bone with or without DMSO, we have
      obtained excellent clinical results without bone absorption in 24 of the cases.
      These results suggest that DMSO is helpful for frozen bone preservation.

PMID- 11993171
TI  - [Characterization of the volume data of three-dimensional CT and MR angiograms
      for the delineation of cerebral aneurysms].
AB  - Three-dimensional CT angiography and MR angiography with perspective volume
      rendering were used to investigate two patients with cerebral aneurysms. Compared
      with the intraoperative photographs, volume data from CT angiogram and MR
      angiogram were characterized on simulated virtual 3D images with virtual neuro
      endoscopic and transluminal imaging techniques. In a case of an unruptured double
      internal carotid (C2) blister aneurysm, CT angiogram showed a configuration of
      the distal aneurysm similar to that in the intraoperative photograph, but failed
      to show the margin of the proximal aneurysm adjacent to the anterior clinoid
      process bone due to a partial volume effect. The MR angiogram represented both
      aneurysms and the parent artery, including the C3-C2 internal carotid artery. The
      whole shape of the aneurysm, however, differed from that in the intraoperative
      photograph, showing instead an elongation of the aneurysmal dome. In a case of a
      ruptured tiny middle cerebral artery aneurysm, CT angiogram failed to show the
      subtle bulging of the aneurysm. In contrast, MR angiogram clearly demonstrated
      the bulging of the walls at the beginning of the ascending and descending
      branches of the M2, which is consistent with the aneurysmal convolution observed
      in the intraoperative photograph. In both cases, transluminal images of the 3D-CT
      and MR angiograms represented the intraluminal contour of the vessel and
      aneurysmal walls as a series of rings, and allowed a transluminal view from
      outside the vessel lumen through the spaces between the rings of the vessel wall.
      The orifices of the aneurysm and parent arteries were shown through the vessel
      and aneurysmal walls, providing an extensive perspective view of the angio
      architecture of the aneurysm. Morphological configuration of the inner space of
      the vessel and aneurysm was well visualized on CT angiogram, which was consistent
      with the operative view. Due to a partial volume effect, the surrounding bony and
      venous structures overlapped with the aneurysm made them indistinguishable from
      each other. In contrast, the MR angiogram provided the flow-related volume
      information, so that dynamics of the flow in the vessel lumen visualized the
      elongation of the aneurysmal dome and subtle bulging of the tiny aneurysm.

PMID- 11993172
TI  - [Prognostic evaluation of glycerol-induced cerebral blood flow measurement in
      asymptomatic unruptured cerebral aneurysm treatment].
AB  - PURPOSE: To clarify the usefulness of glycerol-induced cerebral blood flow
      measurement (G-CBF) as a method for prognostic evaluation of an asymptomatic
      unruptured cerebral aneurysm (AUCA). SUBJECTS AND METHODS: Fifty-three patients
      (age: 26-72 years; ratio of males to females, 23: 30; 56 AUCAs) who were found to
      have an AUCA(s) on brain checkup at our hospital and then received treatment
      (direct or intravascular surgery) were the subject of our study. The patients
      underwent the N-type psychofunction test (NPT) and G-CBF. As the control group, G
      CBF was also performed on 50 subjects (age: 36-73 years; ratio of males to
      females, 27; 23), who were found, by brain checkup, to have no intracranial
      disease. We investigated (1) the occurrence of post-treatment complications
      (symptoms/psychofunctional disorders) in the treated group, and compared (2) G
      CBF between the complication-developing group, the non-complication-developing
      group, and the control group. RESULTS: (1) Complications were observed in 9
      patients (17%), including convulsions in 2 patients, hemiparalysis in 1,
      disorientation in 3. Psychofunctional disorders (less than 80 points on the NPT
      score) were observed in all of the 9 patients developing complications, but could
      be determined as higher brain dysfunctions only in the 3 patients with
      disorientation. (2) The mean cerebral blood flow (mCBF) before glycerol
      administration was 34.17 +/- 4.82 ml/100 g/min in the complication-developing
      group, 32.41 +/- 7.29 ml/100 g/min in the non-complication-developing group, and
      31.98 +/- 5.04 ml/100 g/min in the control group, showing no significant
      intergroup differences. The mean increased rate of cerebral blood flow (mIR)
      after glycerol administration was 7.05 +/- 3.96%, 23.63 +/- 5.5%, and 30.64 +/-
      13.08%, respectively, showing a significantly lower increase in the complication
      developing group (p < 0.01), particularly low in the frontal lobe. Paradoxical
      flow reactivity was observed in 2 patients, both of whom were in the complication
      developing group. CONCLUSIONS: (1) The complication-developing group showed a
      significantly lower pre-treatment mIR (less than 10%), particularly low in the
      frontal lobe, (2) Paradoxical flow reactivity was observed only in the
      complication-developing group. (3) G-CBF was very useful for prognostic
      evaluation prior to the treatment of AUCA.

PMID- 11993173
TI  - [Cerebellar ganglioglioma associated with a huge cyst: case report].
AB  - Gangliogliomas represent approximately 0.2% of all the intracranial tumors.
      Ganglioglioma arising from the cerebellum is rare, with a rate of 1.5-9% of CNS
      gangliogliomas. The authors report a case of cerebellar ganglioglioma with a huge
      cyst. A 28-year-old man presented headache and ataxia. Computerized tomography
      (CT) demonstrated a huge cyst at the vermian region with calcification located at
      the peripheral side of the cyst. Magnetic resonance imaging (MRI) with
      administration of Gd-DTPA showed a slightly enhanced small mass at the left side
      of the cyst. Preoperative diagnosis of the lesion seemed to be a cystic
      astrocytoma. The tumor was removed subtotally through the midline suboccipital
      approach. Pathological examination of the tumor specimen revealed a
      ganglioglioma. The postoperative course was uneventful with no sign of tumor
      regrowth on repeated MRI. According to the previous 17 reports of cerebellar
      ganglioglioma including our case, the shorter interval from onset to the
      diagnosis and clinical symptoms such as increased intracranial pressure were
      conspicuous as compared with supratentorial ganglioglioma because of the
      anatomically narrow space of the posterior fossa. Neuroradiological findings
      showed tumor enhancement in 86% of the cases, calcification in 67%, and cyst
      formation in 53%.

PMID- 11993174
TI  - [A case of orbital osteoma--summary of the case reports in Japan, and the
      usefulness of the microsurgical drilling procedure in surgical treatment of
      orbital osteoma].
AB  - A 57-year-old woman was admitted with a 3-month history of diplopia and
      exophthalmos in the right eye. Plain skull X-P and axial CT demonstrated two bony
      tumors. One involved her right orbit, frontal sinus and ethmoidal sinus, and the
      other was located in the left occipital bone. The right intraorbital tumor was
      removed almost totally via the superomedial orbital approach by means of
      microsurgical drilling. Histopathological examination revealed mature osteoma.
      The microsurgical drilling procedure was helpful in obtaining an optimal result
      from surgical treatment of the orbital osteoma.

PMID- 11993175
TI  - [Shotgun injury of head and neck: case report].
AB  - A 48-year-old male was hit by a shotgun blast from behind while he was hunting.
      He was only 7 meters away when one of his colleagues pulled the trigger
      accidentally. About 180 lead pellets penetrated his head and neck. When he was
      brought to our hospital, he was alert and complained of occipital and nape pain,
      but had no apparent neurological deficits. We administered 200 mg of dimercaprol
      immediately and removed 77 pellets by midline suboccipital incision on the next
      day. Afterwords, we performed four minor operations using a fluoroscope, and
      removed another 70 pellets by day 29. In addition, we administered a 100 mg x 3
      dose of dimercaprol every other week. He was discharged 41 days after the
      accident without any acute signs of lead poisoning. Though serum lead level did
      not rise to critical level, EDTA was continued after his discharge to prevent
      delayed lead poisoning from the retained pellets. Since we seldom encounter this
      type of patient in Japan, delayed lead poisoning by shotgun injury was discussed
      with reference to the literature.

PMID- 11993176
TI  - [A case of malignant peripheral nerve sheath tumor originating from the cervical
      vagus nerve].
AB  - A 45-year-old female presented a peripheral nerve sheath tumor (MPNST), which had
      progressed to malignancy from a neurofibroma arising in the left cervical vagus
      nerve. Neuroimaging showed that a tumor grew in the left neck area of the
      patient, involving the internal carotid and vertebral arteries, and invading the
      intracranium through the left jugular foramen. The tumor was extensively removed
      using a combination of the lateral suboccipital approach and the neck incision,
      and the frontotemporal approach accompanied with EC-IC highflow bypass and EC-MCA
      anastomosis. Postoperatively, pathological features demonstrated a MPNST arising
      from the cervical vagus nerve. Here, we discuss the clinical behavior of MPNST by
      quoting previous reports, and conclude by emphasizing 2 points in the treatment
      of MPNST; 1) that prognosis of patients with MPNST is greatly affected by the
      time between presenting symptoms and diagnosis, and 2) that it is very important
      to carefully observe neurofibroma patients, because there is a possibility of
      progression to malignant MPNST.

PMID- 11993177
TI  - [A temporal head injury involving intracranial penetration by glass].
AB  - The authors report a rare case of intracranial glass injury due to a temporal
      head injury. This 72-year-old man slipped on a bathroom floor, impacting a glass
      door with his head and right shoulder. His right temporal scalp and right
      shoulder were cut by the broken glass. He visited our emergency unit four hours
      after sustaining the injury. Physical and neurological examinations showed no
      abnormalities except for two lacerated wounds on both the right temporal scalp
      (1.5 cm) and the right shoulder skin (10 cm). Foreign bodies were not palpable
      around the lacerated wounds. Skull X-ray and CT studies disclosed a single, 5-cm
      long, radiopaque foreign body penetrating the temporal skull bone into the right
      temporal lobe, but no evidence of intracranial bleeding was found. Under the
      diagnosis of intracranial glass injury, total removal of the foreign body with
      dural repair was carried out. On surgical exploration, glass penetrating the
      skull bone 5-mm distant anteriorly to the scalp laceration was observed.
      Postoperative angiography showed no vascular lesions, and one-week later he was
      discharged with no complications. According to the literature, most of the
      intracranial foreign bodies occur around the orbital, the frontal sinus, and the
      nasal areas. To our knowledge, this is the first report of an intracranial glass
      penetrating injury to the temporal lobe. Since the clinical manifestations
      occasionally do not correspond to the appearance of the laceration after glass
      penetrating injuries, serious caution concerning patients with intracranial glass
      penetrating injuries is important.

PMID- 11993178
TI  - [Middle meningeal artery embolization for refractory chronic subdural hematoma: 3
      case reports].
AB  - The authors present three cases of refractory chronic subdural hematoma (CSDH)
      treated by embolization of the middle meningeal artery (MMA) after several
      unsuccessful drainage procedures. The patients were initially treated by the
      usual method of burr hole and irrigation of the hematoma. After recurrence,
      several percutaneous puncture and drainage procedures were unable to prevent re
      collection of the hematoma. Then the authors embolized the MMA which was thought
      to be the feeding artery of the outer membrane of the hematoma cavity. No
      enlargement of the hematoma was seen after embolization and, gradually, complete
      resolution of the hematoma was obtained. The outcome of the patients was
      excellent in all three cases. This new therapeutic approach to recurrent CSDH is
      discussed.

PMID- 11993179
TI  - [Dissecting aneurysm of the middle cerebral artery with subarachnoid hemorrhage
      showing complete occlusion at the M2 portion of the middle cerebral artery on
      preoperative angiograms: case report].
AB  - We present a surgical case of a dissecting aneurysm of the middle cerebral artery
      associated with subarachnoid hemorrhage and intracranial hemorrhage. A 29-year
      old man suddenly fell into a comatose state, and was referred to our hospital. CT
      scan showed diffuse subarachnoid hemorrhage and an intracerebral hematoma with
      marked midline shift located in the right frontal lobe. The right carotid
      angiogram revealed complete occlusion at the M2 portion of the middle cerebral
      artery, but failed to reveal any aneurysms in the rest of the intracranial
      circulation. We undertook emergent surgery to evacuate the hematoma and to
      confirm whether it was a dissecting aneurysm or not. After evacuation of the
      hematoma of the right frontal lobe, the Sylvian fissure was noticed to be widely
      opened. We detected a large dissecting aneurysm with a dark-purplish wall arising
      from the right M2 trunk, and we trapped the aneurysm. The postoperative course
      was uneventful and the patient gradually improved and was discharged without
      neurological deficits. We presented this case with a review of the literature.

PMID- 11993180
TI  - [A case of traumatic chiasmal syndrome presenting with bitemporal upper
      quadrantanopsia].
AB  - A 22-year-old woman was involved in a motor vehicle accident and suffered a
      craniofacial injury. The patient was treated conservatively with a diagnosis of
      cerebral contusion in the frontal base confirmed with MR images. When the patient
      regained consciousness one week after the accident, she had a complete form of
      bitemporal upper quadrantanopia. A bone window level CT scan showed a linear
      fracture in the middle of the frontal base running longitudinally and extending
      posteriorly down to the sella turcica and clivus. Axial MR images parallel to the
      optic pathway revealed a T2 bright lesion in the anterior half of the optic
      chiasm. The patient recovered gradually and returned to her previous life-style
      six months later without complaining of diplopia, but her visual field defect was
      left unchanged. Traumatic chiasmal syndrome is rare and usually presents
      bitemporal hemianopsia. Very rarely, bitemporal quadrantanopsia has been
      reported. Given the anatomical structure that the neural fibers from the lower
      nasal part of the retina run posteriorly in the optic nerve and cross the
      anterior half of the optic chiasm to enter the contralateral optic tract, the
      lesion in the optic chiasm seen in the MR images seemed to be the causative
      lesion of bitemporal upper quadrantanopsia in our patient. The optic chiasm
      appeared to be injured by a laterally stretching force exerted in an antero
      posterior direction when the medial basal fracture occurred.

PMID- 11993181
TI  - [Genetic polymorphism of efflux drug transporters and their role in drug
      sensitivity].

PMID- 11993182
TI  - Enteric lipopolysaccharide raises plasma IL-6 levels in the hepatoportal vein
      during non-inflammatory stress in the rat.
AB  - It has long been known that plasma interleukin (IL)-6 levels elevate during non
      inflammatory, physico/psychological stresses such as immobilization (IMB) and
      electric foot shock (FS). We previously demonstrated that an IMB-induced rise in
      plasma IL-6 in the rat was caused, at least partly, by an increased production of
      IL-6 in hepatic reticulo-endothelial cells which were induced by enteric flora
      derived lipopolysccharide (LPS). This study investigated whether such enteric
      flora-derived LPS may produce IL-6 also in the mesentery and the mesenteric
      lymphoid nodes (MLN) before it reaches the liver. We found a rise in the IL-6
      levels in the hepatoportal vein (PV) within 30 min during FS, while the IL-6
      levels in the jugular vein showed a smaller and delayed rise with slower
      recovery. Plasma IL-6 levels near the exit of the hepatic vein in the inferior
      vena cava was highest at both control and stressed conditions, compared with
      those in the PV and any other extra-hepatic circulation. The stress-induced IL-6
      elevation in the PV was abolished by an in vivo neutralization of LPS with
      continuous infusion of polymyxin B. Furthermore, the amount of LPS as assessed by
      its bioactivity increased rapidly in the mesentery, the MLN and the liver within
      15 min after the initiation of FS. Finally, fluorescent dye-labeled LPS infused
      into the lumen of the ileum was found in the extra-intestinal tissues and
      systemic vein, and FS increased the optical density in them. The findings suggest
      that lymphoid tissues in the gut associated lymphoid organs are continuously
      exposed to LPS at the basal condition, and that FS facilitates the LPS/bacterial
      translocation across the intestinal wall and thereby increases the production of
      IL-6 before LPS reaches the liver.

PMID- 11993183
TI  - [Clock drawing in dementia: its reliability and relation to the
      neuropsychological measures].
AB  - To examine the reliability and validity of clock drawing (CD) for evaluating
      dementia patients in Japan, we investigated the CD performance and its relation
      to several neuropsychological tests in 150 demented patients including 105
      patients with Alzheimer disease and 30 age- and education-matched non-demented
      subjects (16 patients with mild cognitive impairment and 14 normals). Patients
      were also evaluated using the Mini-mental State Exam (MMSE), Wechsler Memory
      Scale (WMS), Kohs Block Design, and word fluency. CD was scored using the Shulman
      method. CD scores showed a high interrater reliability (r = 0.97). CD by non
      demented subjects was essentially normal. As a screening test for Alzheimer
      disease (AD, mean MMSE = 18.0), CD had a sensitivity of 57.1% and a specificity
      of 96.7%. However, four of eight AD patients who showed normal MMSE score (> or =
      24) drew abnormal clocks. CD scores in dementia were significantly correlated
      with performance on the Block Design (r = 0.68), MMSE (r = 0.56), and the Mental
      Control subtest in the WMS (r = 0.58). Stepwise regression analysis revealed that
      performance on the MMSE and the Block Design explain 53.8% of the variance in the
      CD scores. These findings indicate that low CD score by the Shulman method may be
      reflective of a constructional disability and general severity of dementia. CD is
      not so sensitive as the result of the original report when the patient group
      includes milder cases of AD. CD is, however, an efficient screening test for
      detecting and following the patients with dementia, especially combined with the
      MMSE.

PMID- 11993184
TI  - [Study on dopamine D2 binding capacity in vascular parkinsonism].
AB  - To investigate whether the striatal dopamine receptor function is involved in the
      development of vascular parkinsonism (VP), a positron emission tomography (PET)
      study was conducted on 9 patients with VP by using [11C] N-methylspiperone as the
      tracer. The rate of binding availability in the striatal dopamine D2 receptor
      (k3) was determined semiquantitatively, and the values were compared to the
      predicted normal values based on the results from 7 normal volunteers. Of 9
      patients with VP, the normalized D2 receptor binding [%k3] was more than 90% in 5
      patients, 89 to 87% in 3, and 75% in one. These values showed no evident
      correlation with the Hoehn and Yahr stage. The laterality of the striatal %k3 did
      not correspond to that of the parkinsonism. Thus, the striatal dopamine D2
      receptor binding was not severely impaired and did not correlate with the
      neurological status in patients with VP. This may indicate that striatal dopamine
      D2 receptor function is not primarily associated with the development of the
      parkinsonism in VP.

PMID- 11993185
TI  - [A case of polyneuropathy associated with increased levels of vascular
      endotherial growth factor (VEGF) insera].
AB  - A 54-year-old woman began to notice numbness and motor weakness in the lower
      extremities in July 1999. These symptoms rapidly progressed and she could not
      walk any more. When she admitted to our hospital, she showed peripherally
      dominant, moderate motor weakness, drop foot and loss of superficial and deep
      sensation in the lower extremities, but only slight weakness in the hands.
      Cranial nerves were intact. Deep tendon reflexes were all absent. Nerve
      conduction velocities were reduced and cerebrospinal fluid protein was elevated.
      VEGF was greatly increased in serum (1,850 pg/ml), which has been found to be
      increased exclusively in patients with Crow-Fukase syndrome. Many characteristic
      manifestations of the syndrome except polyneuropathy are well explained to be
      resulted from the abnormal production of VEGF. She did not, however, exhibit any
      constellation of Crow-Fukase syndrome such as edema, skin change, organomegaly,
      bone lesions or M-proteinemia. Steroid therapy improved her symptoms and lessened
      the levels of serum VEGF and cerebrospinal fluid protein. This case indicated
      that overproduction of VEGF could induce polyneuropathy rather than the other
      symptoms of Crow-Fukase syndrome, and that a polyneuropathy associated with
      increased VEGF might exist.

PMID- 11993186
TI  - [A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke
      like episodes (MELAS), showing temporary improvement during the treatment with
      eicosapentaenoic acid ethyl ester].
AB  - We report a 67-year-old man with mitochondrial myopathy, encephalopathy, lactic
      acidosis and stroke-like episodes (MELAS), successfully treated with
      eicosapentaenoic acid ethyl ester (EPA-E) for about eight months. He showed
      bilateral auditory disturbance and slowly progressive gait ataxia at age 50
      during treatment of diabetes mellitus (DM) with subcutaneous injection of insulin
      since age 29. At age 58 he manifested an acute hemiparesis of right extremities
      for one week with no abnormal findings on neuroradiological examinations. A
      permanent pacemaker was implanted at age 61 to treat frequent syncopal attacks
      due to complete atrioventricular block. On admission to our hospital,
      neurological examinations revealed dementia, auditory disturbance, severe
      cerebellar ataxia and mild atrophy of proximal muscles with systemic
      hyporeflexia. Based on a point mutation in position 3243 of mitochondrial DNA, he
      was diagnosed as having MELAS with severe DM, auditory disturbance and cardiac
      conduction block. After initiation of treatment with EPA-E at a dose of 2,700
      mg/day he showed temporarily an improvement in auditory disturbance, blood
      glucose control and cerebellar ataxia. In objective evaluations for cerebellar
      ataxia, we could find significant decreases in times for 20 m walking and heel
      knee patting in the ninth month, and in time for tracing of a whirl from the
      third to the ninth month, compared with those before treatment of EPA-E (p <
      0.0001). Because EPA-E is taken into mitochondrial membranes and activates
      electron transmission enzyme complexes, it might be a candidate for therapy of
      mitochondrial encephalomyopathy, including MELAS.

PMID- 11993187
TI  - [An autopsied case of pachymeningitis associated with a ruptured, cerebral
      aneurysm due to Aspergillus infection].
AB  - We reported a 64-years-old woman with pachymeningitis associated with a ruptured
      mycotic cerebral aneurysm due to Aspergillus infection. She had suffered from
      diabetes mellitus and been treated since she was 49 years old. She complained of
      headache at the age of 62 and loss of her left visual acuity three months later.
      She was treated by the pulse therapy of methylprednisolone as neuritis
      retrobulbaris and her visual acuity recovered. But her headache continued. Three
      months later, her right visual acuity was lost, and the pulse therapy was not
      effective this time. Six months later, she died of subarachnoid hemorrhage
      following acute meningitis. The autopsy was granted, but limited to the cranial
      cavity. Macroscopically, it disclosed brownish thickened dura around sella
      turucica involving trigeminal ganglion and optic nerve, and fresh subarachnoid
      hemorrhage in the basal cisterns and a ruptured aneurysm (3 mm in diameter)
      between internal carotid and posterior cerebral artery on the left side.
      Histologically, the brownish thickened dura was infiltrated by lymphocytes,
      plasma cells, and multinucleated giant cells. The wall around the aneurysm was
      infiltrated by lymphocytes and plasma cells as well as many fungi.
      Immunohistochemistry demonstrated the presence of Aspergillus in the thickened
      dura and the arterial wall around the aneurysm. There were lymphocytes and plasma
      cell infiltration in the basal subarachnoid space and scattered microabcesses in
      the brain. Although the first entry of Aspergillus to the dura was unclear, we
      assume that the final intravascular dissemination of Aspergillus from the dura
      caused meningitis and mycotic aneurysm.

PMID- 11993188
TI  - [A case with upper limb dominant Guillain-Barre syndrome and serum IgG anti-GT1a
      antibodies: sparing oropharyngeal palsy].
AB  - We report a 78-year-old man with Guillain-Barre syndrome (GBS) who showed upper
      limb dominant muscle weakness following an upper respiratory infection. He had no
      weakness in extraocular, oropharyngeal and neck muscles. Tendon reflexes were
      absent in his upper limbs. Electrophysiological studies suggested demyelination
      of motor nerves in his upper and lower extremities. He had serum IgG antibodies
      to GM1 and GT1a but not to GQ1b. Anti-GT1a antibodies did not cross-react to GM1
      by means of the absorption test. Titers of the antibodies decreased after
      recovering from muscle weakness of upper limbs. Since the presence of serum
      antibodies to GT1a but not to GQ1b were reported in patients with pharyngeal
      cervical-brachial weakness of Guillain-Barre syndrome, it has been suggested that
      anti-GT1a antibodies play a role in acute oropharyngeal neuropathy. This is the
      first report of a patient with GBS lacking oropharyngeal palsy who had serum IgG
      antibodies to GT1a but not to GQ1b. Our case suggests that anti-GT1a antibodies
      are related not only with acute oropharyngeal neuropathy but also with upper limb
      dominant motor neuropathy.

PMID- 11993189
TI  - [A family of hereditary spastic paraplegia with dementia, ataxia, and dystonia].
AB  - We reported three siblings with complicated hereditary spastic paraplegia. The
      striking features in these patients were characterized by early onset of gait
      disturbance, mental deficiency, and dystonia. The most likely diagnosis was Mast
      syndrome. Patient 1: A 44 years-old woman. She first developed gait disturbances
      at age of 8. She was admitted in our hospital because of progressive spastic
      paraplegia. Neurological examination revealed mental deficiency, saccadic pursuit
      eye movement, speech disturbance of cerebellar type, ataxia, and spastic
      paraplegia. She showed also dystonia in the face, tongue, and trunk. MRI showed
      cerebellar atrophy. Patient 2: A 51 years-old brother of the patient 1. He had
      mentally retarded. Late teens he developed gait disturbance. Gradually he
      manifested spastic paraplegia, dysarthria, dysphasia, mental deficiency, and
      ataxia. He also showed incontinence of urine and feces. Then he became bedridden,
      apathetic, and showed forced crying. MRI showed diffuse brain atrophy. Patient 3:
      A 48 year-old woman. This woman, a sister of the patient 1, showed progressive
      gait disturbance and dysarthria. She also developed incontinence, apathy, and
      dystonia. She became bedridden, responding to simple questions with only
      occasional single-word answers. Her speech was slurred, and spastic paraplegia
      was noted. MRI showed diffuse brain atrophy including marked atrophy of the
      cerebellum.

PMID- 11993190
TI  - [Carvedilol effectiveness for left ventricular-insufficient patients with
      Duchenne muscular dystrophy].
AB  - To evaluate the efficacy of carvedilol for left ventricular dysfunction in
      Duchenne muscular dystrophy (DMD), we enrolled 8 patients with DMD who had
      elevated plasma atrial natriuretic peptide (ANP) or brain natriuretic peptide
      (BNP), and a low ejection fraction (EF < 40%) in echocardiography. Written
      informed consent was obtained from all of them. Four agreed to be treated with
      oral carvedilol 0.3125-1.25 mg/day (10.1-40.3 micrograms/kg/day) for 6 months
      (treated group). The others served as the controls (untreated group). In both
      groups, we evaluated clinical symptoms, plasma ANP, BNP and EF before, 3 and 6
      months after the trial, and iodine-123 metaiodobenzylguanidine (123I-MIBG)
      imaging at 6 month interval. Parameters in the treated and untreated groups
      before respectively were ANP, 83.8 +/- 17.5 and 89.5 +/- 44.4 pg/ml (mean +/-
      SEM); BNP, 169.0 +/- 46.2 and 186.3 +/- 61.8 pg/ml; EF, 24.0 +/- 2.2 and 16.5 +/-
      1.9%; Heart/Mediastrinum ratio of the 123I-MIBG delayed image, 1.65 +/- 0.08 and
      1.6 +/- 0.10; and Washout rate, 46.5 +/- 8.6 and 41.4 +/- 7.8. These values did
      not change significantly before and 6 months after for either group. Clinical
      symptoms also did not change in either group. Carvedilol therapy did not change
      the left ventricular dysfunction in DMD.

PMID- 11993191
TI  - [A case of Vernet's syndrome due to varicella-zoster virus infection].
AB  - We report a 73-year-old man who suffered from an acute onset of dysphagia, cough,
      hoarseness and left facial and occipital pain. On the 44 days of illness, he was
      admitted to our clinic. A neurological examination revealed left IX, X and XI
      cranial nerve palsy. The diagnosis of Vernet's syndrome due to varicella-zoster
      virus (VZV) infection was made, based on the high titers of VZV antibody in
      serum. Magnetic resonance imaging revealed a unique nodular lesion with
      gadolinium enhancement at the medial side of the left jugular foramen. Clinical
      symptoms improved with intravenous high dose pulse methylprednisolone therapy.
      The clinical course suggests that the inflammation extended from the left X
      cranial nerve ganglion.

PMID- 11993192
TI  - [Therapeutic trial of beta 2-adrenergic agonist clenbuterol in muscular
      dystrophies].
AB  - We report the outcome of trial of clenbuterol in four adult muscular dystrophy
      patients. One patient with Becker type, one with Miyoshi type, and two with
      facioscapulohumeral type were given clenbuterol (30 or 40 micrograms/day) for 6
      to 18 months. We evaluated muscle strength of isometric contraction, grip and
      pinch power, compound muscle action potentials of intrinsic muscles, vital
      capacity, urinary creatinine excretion, and muscle CT. Power and volume of well
      preserved muscles increased mostly, while those of atrophic muscles did not
      improve. Vital capacity increased in two patients. No improvement of ADL was
      observed presumably because ADL was mainly determined by the most atrophic and
      weak muscles. Irrespective of type of muscular dystrophy, administration of
      clenbuterol may be beneficial in early stage of the disease.

PMID- 11993193
TI  - [A case presenting with Raeder's syndrome-like symptoms due to vertebral artery
      aneurysm].
AB  - A 50-year-old man complained of headache around his left orbit, left frontal pain
      and paresthesia associated with left incomplete Horner syndrome. MRI demonstrated
      a mass at the level of medulla oblongata. Left vertebral angiogram revealed an
      aneurysm of left vertebral artery. Following the removal of the aneurysm, these
      Raeder's syndrome-like symptoms improved. Therefore, they were probably caused by
      a compression of the spinal tract of the trigeminal nerve and the central
      sympathetic tract by the aneurysm. This is the first report of Reader's syndrome
      like symptoms caused by vertebral artery aneurysm, thus indicating that MRI and
      cerebral angiogram are necessary for differential diagnosis of this syndrome.

PMID- 11993194
TI  - Functional status in adolescents and adults with Fontan circulation.
AB  - OBJECTIVE: We determined functional status in adolescents and adults with Fontan
      circulation. METHODS: Functional status was studied in 25 patients surviving more
      than 2 years after the definitive procedure and currently no younger than 18
      years old. Age at operation was 2 to 44 years old, and follow-up was 12 +/- 5
      years. To achieve Fontan circulation, atriopulmonary connection was used in 14
      patients, and total cavopulmonary connection in 11 patients. RESULTS: One patient
      undergoing atriopulmonary connection died suddenly 6 years after the Fontan
      procedure due to pulmonary thromboembolism. New York heart association functional
      status was class I in 23, and class II in 2, at the latest follow-up.
      Catheterization done 6.5 +/- 6.8 years after the Fontan procedure showed that
      systemic venous pressure was statistically higher (p = 0.019) in the
      atriopulmonary connection group (13 +/- 3 mmHg) than in the total cavopulmonary
      connection group (10 +/- 3 mmHg). Exercise tests in 19 patients showed reduced
      tolerance in all, with maximal oxygen intake being 24.4 +/- 5.1 ml/kg/min. Serum
      glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were elevated
      above normal in 11 (44%). Arrhythmia was noted over longer terms in 4 patients
      undergoing atriopulmonary connection; in 3, atriopulmonary connection was
      converted to total cavopulmonary connection, and surgical intervention for atrial
      arrhythmia was successful. CONCLUSION: Although functional status in adolescents
      and adults with Fontan circulation was good, arrhythmia and liver dysfunction in
      such subjects could lead to morbidity.

PMID- 11993195
TI  - Acute myocardial infarction due to left main coronary artery occlusion.
      Therapeutic strategy.
AB  - OBJECTIVE: Acute myocardial infarction due to left main coronary artery occlusion
      remains catastrophic and mostly fatal due to severe cardiogenic shock and
      arrhythmia. METHODS: We studied 13 patients undergoing coronary artery bypass
      grafting for acute myocardial infarction due to left main coronary artery
      occlusion to clarify the optimal management of these difficult patients. RESULTS:
      In-hospital mortality was 46.2% (6/13). Revascularization was achieved by
      catheter intervention followed by bypass surgery in 7, and bypass surgery alone
      in 6. Two bypass surgery patients without catheter intervention had collateral
      flow to the left coronary artery, with the right coronary artery dominant. The
      time from onset to recanalization in the survival group was significantly shorter
      than in the early death group. CONCLUSIONS: Emergency intervention to preserve
      left ventricular function or right coronary artery dominant and collateral blood
      flow to left coronary arteries is important for improving the prognosis of
      patients with acute myocardial infarction due to left main coronary artery
      occlusion. If residual left main coronary artery stenosis is significant or other
      proximal coronary stenosis exists after catheter intervention, early coronary
      bypass surgery may improve long-term survival.

PMID- 11993196
TI  - Perioperative features of coronary artery bypass grafting in patients aged 75
      years or older.
AB  - OBJECTIVES: Coronary artery bypass grafting (CABG) is well established as an
      effective operation to overcome ischemic heart disease; however, the number of
      aged patients with a high operative risk undergoing this procedure has increased
      in recent years. This retrospective study evaluates our experience of performing
      CABG in a consecutive series of patients aged 75 years or older. METHODS: To
      assess the hospital mortality and morbidity associated with this procedure, we
      retrospectively analyzed 49 patients aged 75 years or older (Elderly Group) who
      underwent CABG and compared the results with those of 88 patients aged 65-74
      years (Control Group) who underwent CABG during the same period. Patients were
      examined for cerebrovascular diseases, and those with significant stenosis
      underwent pulsatile cardiopulmonary bypass. To avoid pulmonary complications,
      patients were extubated early. RESULTS: The Control Group had a significantly
      higher incidence of arterial grafts than the Elderly Group (0.8 +/- 0.5 versus
      0.3 +/- 0.5; p < 0.0001). The Elderly Group had a significantly higher incidence
      of postoperative complications than the Control Group, with supraventricular
      arrhythmia in 57.1% versus 28.4%, (p = 0.0009), delirium in 36.7% versus 11.4%,
      (p = 0.0004), pneumonia in 6.1% versus 0%, (p = 0.0439), and intubation duration
      of 88.3 +/- 212.5 hours versus 37.2 +/- 92 hours (p = 0.0296), respectively.
      However, there was no significant difference in hospital mortality between the
      two groups, being 8.2% versus, 2.3%, in the Elderly group and Control Group,
      respectively (p = 0.1867). CONCLUSION: These findings indicated that when elderly
      patients were appropriately managed, CABG could be performed with an acceptably
      low risk to mortality.

PMID- 11993197
TI  - Emergency surgery results in life-threatening thoracic aortic disease.
AB  - OBJECTIVE: Emergency surgery for thoracic aortic aneurysm continues to involve
      high mortality. We review our experience in emergency surgery for life
      threatening thoracic aortic disease. METHODS: Between September 1994 and June
      2000, 65 consecutive patients--38 men and 27 women aged 18 to 84 years (mean:
      64.3 years)--underwent emergency surgery for thoracic aortic disease. Of these,
      40 (61%) were treated for acute type A dissection, 16 (25%) for aortic rupture,
      and 9 (14%) for impending aneurysmal rupture. Ascending aorta repair was
      conducted in 21, aortic arch repair in 30, distal arch repair in 2, descending
      aorta repair in 9, and thoracoabdominal aorta repair in 3. Of the 65, 42 were
      under 70 years old and 23 were 70 years of age and older. RESULTS: Overall, 8
      (12%) died in the hospital--3 (7.5%) of acute type A dissection, 3 (19%) of
      ruptured aneurysm, and 2 (22%) of impending rupture. Of these, 3 (7.1%) were
      younger than 70 years and 5 (22%) 70 years and older. The following perioperative
      factors significantly influenced hospital mortality: pump time (p = 0.019),
      postoperative severe cardiac failure (p = 0.006), postoperative respiratory
      failure (p = 0.045), and postoperative acute renal failure (p = 0.0007). Of the
      57 survivors followed up for an average of 2.8 years (1 month to 6 years), 3-year
      survival was 73% overall--88% in patients younger than 70 years and 38% in those
      70 years and older (p = 0.0004). Seven of the 9 patients suffering strokes during
      surgery died in the hospital (2) or after discharge (5). Overall hospital and
      late deaths involved 2 of 4 patients younger than 70 years and all of 5 patients
      70 years and older. CONCLUSION: The majority of patients undergoing emergency
      surgery for life-threatening thoracic aortic disease can undergo graft
      replacement with acceptable mortality, morbidity, and late survival, but early
      and late mortality for patients older than 70 remains extremely high.

PMID- 11993198
TI  - Steroid therapy without primary dose escalation for postthymectomy crisis in 2
      thymomatous myasthenia gravis patients.
AB  - We report 2 cases of thymomatous myasthenia gravis associated with postoperative
      crisis and medicated with steroid therapy using prednisolone without primary dose
      escalation. Two women, a 38 years old and the other 64 years old, underwent
      extended thymectomy under the diagnosis of myasthenia gravis associated with
      invasive thymoma. Bulbar symptoms in both were severe despite preoperative
      anticholinesterase medication. Myasthenic crises with an antiacetylcholine
      receptor antibody (anti-AchR Ab) elevation were encountered in the postoperative
      clinical course. Daily administrations of a large amount of prednisolone without
      primary dose escalation and the subsequent tapering therapy effectively improved
      myasthenic symptoms and decreased their anti-AchR Ab titer. We also discuss
      difficulties in treatment in these cases.

PMID- 11993199
TI  - Thoracoscopic approach for congenital bronchoesophageal fistula in an adult.
AB  - We present a case of a congenital bronchoesophageal fistula in an adult male who
      underwent video-assisted thoracic surgery for a resection of the fistula. The
      patient had not suffered from any serious respiratory infection since the
      adolescence. However, at 49 years old, the patient experienced persistent cough
      and back pain. An abnormal shadow in the right lower lobe was observed on a chest
      X-ray. Chest computed tomography scanning indicated bronchiectasia in the lower
      superior segment and an abnormal air duct in the posterior mediastinum.
      Esophagography revealed a 4-cm-long and 1-cm-diameter fistula between the
      midesophagus and the right lower lobe. Esophagoscopy and bronchoscopy revealed
      the orifice of the fistula. Three-dimensional computed tomography scanning
      demonstrated that there was no abnormal artery supplying blood to the affected
      lung. He underwent video-assisted thoracic surgery, and was uneventfully
      discharged. Thoracoscopy offered excellent anatomical visualization of the
      fistula and safe surgical resection.

PMID- 11993200
TI  - Staged Fontan procedure for mitral atresia associated with severe tricuspid
      regurgitation, pulmonary hypertension, and pulmonary artery distortion.
AB  - Optimal initial palliation and a subsequent staged approach is mandatory for high
      risk Fontan candidates. We describe the case of mitral atresia with severe
      tricuspid regurgitation and pulmonary hypertension successfully managed by
      repeated palliation from the neonatal period and 2-stage Fontan surgery. A 1
      month-old boy diagnosed with mitral atresia and double-outlet right ventricle
      underwent pulmonary artery banding at 1 month of age, followed by repeated
      pulmonary artery banding accompanied by tricuspid annuloplasty and atrial septal
      defect enlargement at 6 months. Because of the presence of pulmonary artery
      distortion, right ventricular dysfunction, and borderline pulmonary vascular
      resistance, a hemi-Fontan procedure was conducted with extended pulmonary artery
      plasty when the boy was 3 years and 8 months old. Cardiac catheterization done 3
      months after showed improvement in risk factors, and the final Fontan operation
      (total cavopulmonary connection) was successfully done in conjunction with
      repeated tricuspid annuloplasty when the boy was 4 years and 5 months old. The
      patient remains in excellent clinical condition at the last follow-up 5 years
      after the final Fontan procedure with sinus rhythm and good ventricular function.

PMID- 11993201
TI  - Pleural gas gangrene secondary to esophageal injury by an ingested fish bone.
AB  - We report a 73-year-old woman with right pleural gas gangrene, treated
      successfully by thoracoscopic debridement. The clinical course and chest computed
      radiography and thoracoscopy findings suggested that her condition resulted from
      a relatively rare esophageal injury after she accidentally ingested a fish bone.
      Video-assisted thoracoscopic intervention has proved useful in cases involving
      pleural gas gangrene.

PMID- 11993202
TI  - Acute occlusion of coronary artery bypass graft with nonionic contrast medium.
AB  - The use of nonionic contrast media should be beneficial in patients with cardiac
      disease because such media are less chemotoxic. Using iopamidol under
      heparinization, we treated 4 cases of acute thromboembolic occurrence including
      occlusion of coronary artery bypass grafts and associated native coronary
      arteries. While the majority of patients do not experience this complication,
      care must be taken to avoid major adverse effects.

PMID- 11993203
TI  - Successful weaning from a left ventricular assist device after surgical repair of
      a left ventricular free wall rupture.
AB  - We present a case of an insertion of a left ventricular assist device for severe
      cardiac failure after the repair of a left ventricular free wall rupture. A 72
      year-old man was admitted with chest pain and unconsciousness, and required
      emergency surgical repair of a left ventricular free wall rupture under
      percutaneous cardiopulmonary support. Severe cardiac failure occurred
      postoperatively, and weaning from percutaneous cardiopulmonary support was
      impossible. We implanted a left ventricular assist device, and this could be
      removed at one week after implantation. The left ventricular assist device was
      very useful as a "bridge to recovery".

PMID- 11993204
TI  - [Clinical study of bladder injury].
AB  - Since bladder injury has no specific clinical symptoms, accurate diagnosis at
      first consultation is relatively difficult. To elucidate the clinical characters
      type of injury, clinical symptoms, laboratory findings, methods of therapy and
      diagnosis, we reviewed 15 patients with bladder injury over a 9-year-period 1990
      1998 (10 were traumatic injuries and 5 spontaneous injuries). We found no
      specific clinical symptom of bladder injury. Bladder injury may occur anywhere in
      the bladder wall, but most commonly occurred at the dome of the bladder (60.0%).
      Gross hematuria was not seen in 40.0% of the cases. The accuracy of diagnosis at
      first consultation was relatively low (46.7%) and the tendency to make a
      misdiagnosis as acute abdomen on digestive organs was found. Of the traumatic
      injuries 60% were afflicted in the drunken state, so alcohol intoxication was
      considered as an important enviromental factor of bladder injury. Surgical repair
      of injury sites was employed in 11 cases (73.3%: 7 were intraperitoneal injuries,
      4 were extraperitoneal injuries), 4 cases were managed with indwelling urethral
      catheter. With appropriate treatment, the prognosis is excellent.

PMID- 11993205
TI  - [A clinical analysis of patients with early-stage prostate cancer managed without
      initial treatment].
AB  - To search for a more suitable qualification indicating watchful waiting, we
      performed a retrospective study against early-stage prostate cancer patients
      managed without initial treatment. Thirty-three patients who had not been treated
      for more than 6 months after diagnosed as T1c or T2 prostate cancer were studied.
      The median values of total observation period, age at diagnosis, and initial PSA
      were 27.0 months, 69.0 years old, and 7.0 ng/ml, respectively. Among 28 patients
      who had had measurement of serum PSA at least three times, seven patients showed
      a significant PSA elevation when transition of PSA level was analyzed using
      linear regression analysis. The other patients had been stable or PSA level
      declined. Between these two groups, there was no significant difference regarding
      age, initial PSA, PSA density, Gleason score, number of cancer-positive core, and
      cancer-occupying rate in biopsy specimen. The median PSA doubling time in
      patients showing PSA elevation was 36.3 months. There were no patients showing
      PSA elevation among those with a cancer-occupying rate of less than 5%. Clinical
      disease progression was obviously observed in two cases although one did not show
      PSA elevation. During the observation period, treatment was eventually started in
      seven patients. The 5-year rate of no treatment was 53.8%. Although a significant
      independent factor predicting the future treatment was not identified, univariate
      analysis revealed that the initial PSA value in patients undergoing treatment was
      significantly higher than that of those without treatment (p = 0.032). We
      concluded that early-stage prostate cancer has clinical variability, and regular
      clinical evaluations as digital rectal examination should be performed when the
      patient was managed with watchful waiting.

PMID- 11993206
TI  - [Early results in the initial 15 cases of laparoscopic radical prostatectomy in
      Akita University Medical Center].
AB  - We herein report our experience and early results of laparoscopic radical
      prostatectomy in 15 cases of localized prostate cancer (11 T1c and 4 T2a tumors)
      performed between March 2000 and October 2001. The operative procedure was almost
      identical to the Montsouris technique. Conversion to the open procedure was
      required only in the first case because of a widely opened bladder neck that
      involved the ureteral orifice. No severe intraoperative or postoperative
      complications were observed. The mean operating time and blood loss was 383
      minutes and 640 ml including intraoperative urine, respectively. Only one patient
      required blood transfusion. All 14 patients with a successful procedure could
      take fluid and walk freely on postoperative day 1. Twelve (86%) of the 14
      patients could take food on postoperative day 1 and a Foley catheter was
      successfully removed on day 6 to 8 in 12 (86%) cases. Histologically, positive
      surgical margin was observed in 5 (33%) cases and all of them were considered non
      organ confined (pT3 or more). Without adjuvant hormonal therapy, biochemical
      (PSA) failure was observed in 5 (36%) cases (median follow-up period: 11 months).
      Continence has been well maintained in 12 patients with no need for a pad by 3
      months postoperatively and 2 patients are using only 1 pad/day for caution's
      sake. In terms of early postoperative recovery, intraoperative blood loss and
      maintenance of continence, laparoscopic radical prostatectomy may give a
      satisfactory result. Although long-term follow-up is required to assess disease
      control and maintenance of sexual function, laparoscopic radical prostatectomy
      may become an alternative for the treatment of organ-confined prostate cancer.

PMID- 11993207
TI  - [The experience of laparoscopic radical nephrectomy for renal tumors].
AB  - We evaluate the safety and feasibility of laparoscopic radical nephrectomy for
      renal tumors. Between September 1993 and October 2001, 18 patients with renal
      tumors underwent laparoscopic radical nephrectomy. The mean patient age was 57.1
      years ranging from 36 to 78. Clinical stage was T1N0 in all patients. The mean
      tumor diameter was 4.0 cm ranging from 1.8 to 7.0. Laparoscopic radical
      nephrectomy was performed by using the transperitoneal anterior approach on 11
      patients and retroperitoneal approach on 7 patients. The specimen was removed
      through an extended stab wound after blunt segmentation of renal parenchyma in a
      specimen bag (LapSac). The mean operative time was 405 (270-550) and 453 (325
      635) min for the transperitoneal approach and retroperitoneal approach
      respectively, and the mean blood loss was 281 (52-700) and 223 (10-850) ml,
      respectively. There was an intraoperative complication of minor splenic injury in
      2 patients receiving the transperitoneal approach, which was conservatively
      managed. Histopathology revealed renal cell carcinoma in 17 patients and renal
      oncocytoma in one patient. There was no recurrence with a mean follow-up of 28.9
      months. Compared with 13 patients who underwent open radical nephrectomy during
      the same period, laparoscopic nephrectomy has a longer operative time (424 versus
      214 min, p < 0.001), equal blood loss (259 versus 210 ml, p = 0.59), quicker
      resumption of ambulation (1.8 versus 2.5 days, p = 0.016) and food intake (1.4
      versus 2.2 days, p = 0.003), shorter postoperative hospital stay (10.9 versus 18
      days, p = 0.0016), and a tendency of less frequent analgesic requirements (1.9
      versus 4.7 times, p = 0.09). Laparoscopic radical nephrectomy is a safe and
      useful surgery for renal tumors providing minimal invasiveness.

PMID- 11993208
TI  - [A case of hydronephrosis associated with appendiceal abscess].
AB  - An appendiceal abscess was complicated with right hydronephrosis in a 76-year-old
      woman who complained of general fatigue and fever. Ultrasonography demonstrated
      right hydronephrosis, and retrograde pyelography confirmed the hydronephrosis and
      showed ureteral stenosis. Computed tomography scan revealed a low-density area
      measuring 38 x 35 mm in size, anterior to the right ureter. Ureteroscopy and the
      biopsy of the mucosa was carried out, but malignant cells were not found. An
      exploratory laparotomy was performed. The mass had developed from the cecum and
      involved the ureter, requiring ileocecal excision, left partial ureterectomy and
      ureteric substitution with a Boari's flap. The histological diagnosis was an
      appendiceal abscess. The postoperative course was uneventful.

PMID- 11993209
TI  - [Renal pelvic cancer representing G-CSF production and hypercalcemia
      simultaneously: a case report].
AB  - A 73-year-old man was admitted to the hospital complaining of gross hematuria and
      left flank pain. Abdominal ultrasonography and computed tomography revealed a
      left renal tumor with extracapsular extension. Laboratory data showed marked
      leukocytosis of 121,000/mm3 and hypercalcemia of 12.3 mg/dl without any findings
      of inflammatory disease or bone metastasis. Enzyme immunoassay of the serum
      demonstrated a high level of granulocyte colony-stimulating factor (250 pg/ml)
      and parathyroid hormone-related protein (1,069 pmol/l). Pathological diagnosis of
      needle biopsy specimen of the primary tumor was transitional cell carcinoma which
      was suspected to have originated from renal pelvis. Immunohistochemical
      examination with anti-granulocyte colony-stimulating factor monoclonal antibody
      demonstrated granulocyte colony-stimulating factor production in cancer cells.
      The patient underwent a course of systemic chemotherapy, but died two months
      after diagnosis. To our knowledge, this is the first report of renal pelvic
      cancer representing granulocyte colony-stimulating factor production and
      hypercalcemia simultaneously.

PMID- 11993210
TI  - [Leiomyosarcoma and transitional cell carcinoma in the urinary bladder: a case
      report].
AB  - A 74-year-old man was admitted for asymptomatic macroscopic hematuria. He had
      undergone transurethral resection of bladder tumor (TURBT) due to transitional
      cell carcinoma 30 years ago. Pelvic CT showed two invasive bladder tumors. A 5 cm
      tumor was on the dome and a 1 cm tumor was on the left lateral wall. TURBT was
      performed. Pathological examination revealed that they were leiomyosarcoma and
      transitional cell carcinoma. Radical cystectomy plus bilateral
      cutaneousureterostomy was performed. He died of lung metastases and local
      recurrence after 6 months.

PMID- 11993211
TI  - [A case of extensive Fournier's gangrene].
AB  - A 52-year-old man was admitted to our hospital complaining of high grade fever
      and painful swelling of the scrotum. Although debridement of the scrotum and
      inguinal region was immediately carried out, the inflammation extended to the
      right abdominal region 2 days later. We tunneled the newly infected areas and
      placed Penrose drains through the tunnels, so that complete drainage was achieved
      with minimal tissue loss. The infection was controlled by frequent irrigation of
      the wound and antibiotic administration. Forty days after the admission the
      defect of the skin was reconstructed by using a meshed skin graft, and the
      patient was discharged on the 68th hospital day. We concluded that limited
      debridement with placement of through-and-through drains might have produced a
      good result with minimal tissue loss.

PMID- 11993212
TI  - [Empyema of the ureteral stump with multiple stones after nephrectomy].
AB  - A 64-year-old woman, who had undergone right nephrectomy because of right
      incomplete double pyeloureter and dysplastic kidney with a ureteral stone at the
      age of 25, presented with a chief complaint of repeated urinary tract infection
      associated with right lower abdominal pain. A diagnosis of empyema of the
      ureteral stump with multiple stones was made based on X-ray findings and
      cystoscopy. In December 1999, the right residual ureter and ureteral stones were
      removed. Histopathologically, non-specific inflammatory change and fibrosis of
      the wall were observed. The ureter including the stones should have been resected
      at the previous nephrectomy.

PMID- 11993213
TI  - [Ureteral inverted papilloma: a case report].
AB  - A 43-year-old man presented with left hydronephrosis, incidentally found by
      ultrasonography. He had undergone transurethral bladder tumor resection when he
      was 29 years old. Cystoscopy revealed a tumor protruding from the left ureteral
      orifice. Left partial ureterectomy was performed, and its histopathological
      diagnosis was ureteral inverted papilloma. He has remained free of disease for 18
      months after the surgery.

PMID- 11993214
TI  - [A case of giant perirenal malignant lymphoma: a case report].
AB  - We report a case of malignant lymphoma arising as a giant perirenal mass in a 62
      year-old woman who presented with an enlarging abdominal mass. Computed
      tomography (CT) revealed a large homogeneous mass with a diameter of 20 cm
      arising in the retroperitoneum. It surrounded the left kidney without renal
      infiltration and accompanied with para-aortic lymph node enlargement. Compared
      with the renal cortex, the tumor showed a homogeneous isodense mass by plain CT
      and only slight enhancement by the contrast-enhanced CT. On the basis of these
      imaging studies, the tumor was diagnosed as lymphoma. Then, a US guided
      percutaneous biopsy was performed and the tumor was diagnosed as malignant B-cell
      lymphoma by the histopathological analysis. This patient was treated by systemic
      chemotherapy since tumor cells were also disseminated in the bone marrow. The
      tumor responded well to the chemotherapy and about 70% of regression was achieved
      after six courses of chemotherapy.

PMID- 11993215
TI  - [A case of subcutaneous metastases from bladder cancer after radical
      cystouretherectomy].
AB  - A case of transitional cell carcinoma (TCC) of the bladder metastasizing
      subcutaneously to the right lower abdomen and to the left back approximately 2
      years after radical cystouretherectomy is reported. A 65-year-old male underwent
      radical cystouretherectomy with the creation of ileal couduit after preoperative
      intraarterial chemotherapy and radiotherapy. At the out patient clinic two years
      postoperatively, a subcutaneous tumor was palpated in the right lower abdomen and
      the left back. The tumors were removed and histopathologically diagnosed as
      subcutaneous metastases of TCC. The patient received three courses of
      postoperative systemic chemotherapy. At 15 months after the last chemotherapy,
      the patient remains free of metastases and relapse.

PMID- 11993216
TI  - [A case of primary malignant retroperitoneal mesothelioma needed to differentiate
      adrenal tumor].
AB  - Malignant mesothelioma is a neoplasm which tends to develop along serosal
      surfaces, such as the pleura and peritoneum. We report a rare case of malignant
      retroperitoneal mesothelioma in a 27-year-old woman. The patient was admitted
      with a chief compliant of intermittent high fever once a month, and left
      retroperitoneal tumor was detected by dynamic abdominal computed tomography.
      Since an adrenal tumor was suspected, laparoscopic tumor extirpation was
      performed. Immunohistochemically tumor cells were positive for calretinin and
      thrombomodulin, but negative for carcinoembryonic antigen (CEA) and Ber-Ep4.
      Based on these findings, primary malignant retroperitoneal mesothelioma was
      diagnosed.

PMID- 11993217
TI  - [Mucinous adenocarcinoma of the renal pelvis in the horseshoe kidney: a case
      report].
AB  - A 41-year-old man with macroscopic hematuria and abdominal fullness was referred
      to our hospital. Computed tomography (CT) revealed a left renal pelvic tumor in
      the horseshoe kidney. We performed left heminephrectomy and ureterectomy. The
      pathological diagnosis was the mucinous adenocarcinoma in the renal pelvis. He
      received postoperative adjuvant chemotherapy (CAP therapy). He died of
      retroperitoneal recurrence 8 months postoperatively. In the literature we found
      95 cases of primary adenocarcinoma in the renal pelvis including our case.

PMID- 11993218
TI  - [Current and future problems of treatments for esophageal carcinoma].

PMID- 11993219
TI  - [Diagnosis of esophageal cancer using positron emission tomography].
AB  - Fluorodeoxyglucose positron emission tomography (FDG-PET) is more accurate than
      computed tomography (CT) for evaluating lymph node metastases and for N staging,
      but less accurate than combined CT and endoscopic ultrasonography (EUS). Lymph
      nodes located adjacent to the primary lesion tend to be false negatives. We
      consider that combined FDG-PET and EUS is the most accurate for the detection of
      lymph node metastasis in esophageal cancer. FDG-PET is also more accurate than CT
      for detecting distant metastases and improves the detection of stage IV disease
      compared with the conventional staging modalities. For the diagnosis of
      recurrence except for perianastomotic recurrence, FDG-PET provides additional
      information and is more sensitive than conventional work-ups. FDGPET is a
      valuable tool for the noninvasive assessment of tumor response after neoadjuvant
      therapy. 11C-methionine (MET) is another tracer for PET that can be used to
      assess the metabolism of amino acids, since MET accumulates in esophageal
      malignant tumors. Choline-PET is more accurate than FDG-PET for the detection of
      mediastinal lymph node metastases.

PMID- 11993220
TI  - [Imaging diagnosis of esophageal carcinoma by computed tomography and magnetic
      resonance imaging].
AB  - The staging diagnosis of esophageal carcinoma is important to determine
      therapeutic modalities and to predict prognosis. The current status of imaging
      diagnosis of tumor invasion to the adjacent organs and lymph node metastasis is
      described. The diagnostic criteria used to determine tumor invasion to the
      adjacent or gans by computed tomography (CT) and magnetic resonance imaging(MRI)
      are displacement and compression deformity of the tracheobronchial tree and
      obliteration of the periaortic fat plane over more than 90 degrees of the aortic
      circumference. Detection of the fat plane between the esophagus and the aorta
      supported by density profile analyzing software on CT may enable the diagnosis of
      invasion. Cine-MRI imaging is also useful to obtain dynamic information on the
      tumor and aorta. Tumor invasion to the aortic wall can be excluded when a low
      intensity stripe is recognized between the tumor and the aortic wall. Although
      the criterion for lymph node metastasis on CT is 10 mm or more in long transverse
      diameter, the diagnostic accuracy is poor. The accuracy improves when imaging
      patterns such as heterogeneous internal structures in the enhanced lymph nodes
      and/or hyperenhancement in the lymph nodes in the early phase by dynamic study
      are added to the diagnostic criteria. However, small metastatic lymph node remain
      undetected and it is difficult to diagnose negative lymph node metastasis
      properly on CT and MRI. It is important to have full knowledge of the advantages
      and limitations of each imaging modality and to obtain objective information form
      them.

PMID- 11993221
TI  - [Endoscopic evaluation of the depth of invasion in cases of superficial
      esophageal cancer in determining indications for endoscopic mucosal resection].
AB  - Endoscopic mucosal resection (EMR) should be performed for the treatment of
      squamous cell carcinoma of the esophagus limited to the lamina propria mucosae
      (m1 and m2 cancers), because lymph node metastasis is rare in these cases. The
      lymph node metastasis rate is 6% when cancers reach the muscularis mucosa(m3) or
      slightly invade the submucosa (sm1). Lymph node metastasis is noted in 47% of
      esophageal cancers moderately or severely invading the submucosa(sm2 and sm3).
      Radical esophagectomy is recommended for sm2 and sm3 disease. Type 0-II cancers
      are candidates for EMR, because 86% remain within the mucosa, while 90% of type 0
      I lesions and 96% of type 0-III lesions are submucosal cancers. Among type 0-II
      cancers, most type 0-IIb lesions are m1 cancer. Among type 0-IIa cancers, 96% are
      mucosal. Type 0-IIc lesions are frequent among superficial esophageal cancers and
      19% reach the submucosa. Endoscopic diffrentiation of m1 and m2 cancers is
      reliable, since 96% of all m1 and m2 cancers were correctly diagnosed before
      treatment. In cases with type O-IIc lesions which is most frequent among
      superficial esophageal cancers, m1 cancer showed very slight depressions with a
      smooth surface and reddening. Sometimes fine granular changes are seen. They are
      also delineated as an unstained area by endoscopic toluidine blue-iodine double
      staining. They showed very slight depressions with a smooth surface and
      reddening. Sometimes fine granular changes are seen. They are also delineated as
      an unstained area by endoscopic toluidine blue-iodine double staining. Dark blue
      dots, spots, or reticular staining are frequently identified in m2 cancers. In
      cases with m3 or sm1 cancer, coarse granular changes, small nodular elevations,
      or slightly deeper depressed areas in the m1 and m2 lesions suggest sites of
      deeper invasion.

PMID- 11993222
TI  - [Esophagectomy with lymph node dissection through right thoracotomy].
AB  - In esophageal cancer, the incidence of lymph node metastasis is much higher than
      that in gastric or colonic cancer. Lymph node metastasis is frequently found
      along the recurrent laryngeal nerve and around the gastric cardia. The accuracy
      rate of preoperative diagnosis of lymph node metastasis is up to 80%, in spite of
      vigorous diagnostic efforts. In Japan, "esophagectomy with 3-field lymph node
      dissection through a right thoracotomy" is the standard surgery for advanced
      esophageal cancer. However, based on the "Comprehensive Registry of Esophageal
      Cancer in Japan," this standard operation does not prevail nationwide. Although,
      it is difficult to obtain evidence showing the effects of lymph node dissection
      for ethical reasons, we must continue accurate lymph node dissection with the
      best surgical techniques to improve patient survival.

PMID- 11993223
TI  - [Radical surgery with mini-thoracolaparotomy for esophageal cancer].
AB  - In our institute, radical esophagectomy through mini-thoracolaparotomy has been
      performed as a less-invasive surgery for esophageal cancer since 1996. We
      describe the indications for and operative procedures of mini-thoracolaparotomy.
      Next we report the preliminary results of a prospective randomized trial that
      compared mini-thoracolaparotomy with conventional thoracolaparotomy in 30
      patients without neoadjuvant therapy. There were no differences between the two
      groups in operative time, bleeding volume, and number of dissected lymph nodes.
      Thoracolaparotomy was effective in decreasing the quantity of morphinerequired in
      the ICU and shortening hospitalization after surgery. Thoracolaparotomy was
      effective in preventing a decrease in and early recovery of postoperative vital
      capacity. In clinical data on radical esophagectomy performed through a right
      thoracotomy and reconstruction with a stomach tube from 1996 to 2000, the 5-year
      survival rate of 63 patients in the thoracolaparotomy group (67.6%) did not
      differ from that of 124 patients in the conventional surgery group (49.9%).

PMID- 11993224
TI  - [Thoracoscopic esophagectomy].
AB  - The current roles of thoracoscopic esophagectomy in the treatment of cancer in
      Japan are described. Lymphadenectomy of the same quality as open surgery should
      be performed thoracoscopically to obtain good oncological outcomes. The
      indications for thoracoscopic esophagectomy are 1) no extensive pleural
      adhesions; 2) pulmonary function sufficient for single-lung ventilation; and 3)
      tumor not invading other organs. Hand-assisted or mini-thoracotomy facilitates
      the dissection of lymph nodes, especially on the left side of the trachea.
      However, for any type of procedure, a good en-face view is essential for safe and
      accurate lymphadenectomy. The magnifying effect of video, with the camera in
      close proximity, is important to maintain a proper dissecting plane. Although
      sufficient experience is necessary to master the learning curve, lymphadenectomy
      of the same quality as open surgery can be performed with mini-thoracotomy in a
      feasible time period. Thoracoscopic esophagectomy contributes to reducing
      postoperative pain and constrictive pulmonary dysfunction. It may be too soon to
      assert that the thoracoscopic approach can provide oncological outcomes
      comparable to those after open surgery because long-term follow up is not yet
      sufficient. Thoracoscopic esophagectomy, however, has the potential to improve
      the postoperative quality of life of patients with esophageal cancer.

PMID- 11993225
TI  - [Chemotherapy for the patients with esophageal cancer].
AB  - The combination of cisplatin and continuous-infusion 5-fluorouracil is the
      standard regimen for the treatment of both squamous cell carcinoma and
      adenocarcinoma. Paclitaxel has shown favorable results as a single agent or in
      combination with cisplatin. The efficacy of neoadjuvant chemotherapy in terms of
      survival benefit remains controversial despite large-scale, randomized,
      controlled trials comparing it with surgery alone. The disease-free survival
      benefit of postoperative adjuvant chemotherapy was recognized in a Japan Clinical
      Oncology Group randomized controlled trial in comparison with surgery alone.

PMID- 11993226
TI  - [Radiotherapy and chemotherapy for esophageal cancer].
AB  - The nonsurgical gold standard treatment for esophageal cancer is radiotherapy,
      but chemoradiation therapy using anticancer agents concurrently is becoming
      standard management. With chemoradiation adverse responses in the acute stage may
      be enhanced in comparison with conventional radiation therapy alone, but improved
      treatment outcomes are reported. A consensus has nearly been reached on the
      standard radiation technique and dose, and a guideline changes, but drug type,
      timing, and optimum dosage in chemoradiation are unclear. Further future study is
      thus necessary. In this report, recent trends in radiotherapy and chemoradiation
      are outlined and future problems described.

PMID- 11993227
TI  - [Gene therapy for esophageal cancer].
AB  - Esophageal cancer is a highly malignant disease in which progression is observed
      in most patients even at the first medical examination. Neoadjuvant cytoreduction
      treatments are frequently used for the purpose of tumor down-staging, increasing
      the resection rate, and possibly improving survival. Although combination therapy
      with radiation and anticancer agents is available, no satisfactory treatment
      regimen has yet been established due to the development of resistance. Based on
      the concepts of genetic alteration in carcinogenesis, cancer gene therapy has
      been developing rapidly. We previously reported the growth inhibitory effect of
      adenovirus-mediated wild-type p53 gene transfer into esophageal squamous
      carcinoma cell lines. After extensive preclinical study of p53 gene therapy in
      vitro and in vivo, we are conducting a phase I/II clinical trial. The target of
      this trial is patients with unresectable esophageal cancer resistant to
      chemoradiotherapy. As of December 1, 2001, 8 candidates had been admitted to our
      hospital. After extensive examination, 4 patients were enrolled in this trial.
      After giving informed consent, the first patient received injections of Ad5 CMV
      p53 on December 19, 2000. No serious adverse events have occurred so far in these
      patients, and the trial has been conducted safely.

PMID- 11993228
TI  - [Immunotherapy for esophageal carcinoma].
AB  - Recent progress in gene technology has clarified the existence of some cancer
      rejection genes and peptides such as MAGE, MART, etc. Many clinical trials with
      cancer vaccines have been performed. Since the clinical efficacy of HLA class I
      restricted peptide vaccines is still poor, many researchers are mainly
      administering dendritic cell therapies. However, there have been few clinicals
      trials of cancer-specific immunotherapy for esophageal carcinomas. We have
      performed cancer vaccine therapy with SART-1 peptide and locoregional adoptive
      immunotherapy with activated autologous lymphocytes for patients with advanced
      esophageal carcinoma in a phase I and a phase I/II trial, respectively. The
      clinical responses were poor in the vaccine trial because of the rapid growth of
      esophageal cancers and the requirement for more than 2 months to activate and
      increase killer T cells after in vivo vaccination, while locoregional adoptive
      immunotherapy was effective for the treatment of esophageal cancers even in
      advanced stages with organ metastases. Based on these results, we think that a
      combination immunotherapy with adoptive immunotherapy and vaccine therapy is
      needed for the treatment of advanced esophageal carcinomas.

PMID- 11993229
TI  - [Liver transplantation for hepatocellular carcinoma: experience at an Australian
      transplantation unit].
AB  - The author experienced 11 cases of orthotopic liver transplantation (LTx) for
      hepatocellular carcinoma (HCC) in Sydney, Australia, series. LTx was selected in
      5 cases for the treatment of HCC and in 6 for terminal liver failure. Three
      patients had new lesions, which were not detected on preoperative imaging, and 5
      had vascular or extrahepatic infiltrations. Two patients with hepatitis C had
      recurrence of hepatitis at an early stage. Two had tumor recurrence, one of which
      had 7 lesions with invasion to the vessels and bare area. Thus some problems
      remain in LTx for HCC, including the recurrence of hepatitis in hepatitis C and
      tumor recurrence in cases with high-risk factors based on the pathologic
      findings.

PMID- 11993230
TI  - [Overexpression of 14-3-3 in primary gastric cancers and clinical application for
      the detection of micrometastases in the peritoneal cavity].

PMID- 11993231
TI  - [Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to
      trichloroethylene or tetrachloroethylene].
AB  - Since the late 1980s, there has been an increasing tendency in the number of case
      reports on Stevens-Johnson syndrome accompanied by acute hepatitis in workers
      exposed to trichloroethylene from Asian countries. Recently, mass outbreaks of it
      have been disclosed in the Philippines and China. Besides trichloroethylene,
      although the number is small, a similar health disorder has also occurred in
      workers using tetrachloroethylene. Since the above-mentioned facts are not yet
      well recognized in the occupational health community, this review is aimed at
      making clear (1) the clinical features of the health disorder, (2) details of
      patients' jobs, working environments, and exposure to hazardous chemicals, and
      (3) the relationship between exposure to trichloroethylene or tetrachloroethylene
      and the health disorder. Based on a critical review of articles, the following
      were pointed out. First, it is important to carefully observe the health status
      of workers exposed to trichloroethylene or tetrachloroethylene and to take
      countermeasures to reduce exposure. Secondly, circumstantial evidence suggests a
      cause-effect relationship between the two chemicals and the health disorder; but
      at the present time it is impossible to rule out the participation of
      unelucidated factors promoting the occurrence of the health disorder or the
      existence of a hidden genuine causative substance. Therefore further
      investigation to trace such a case is needed. Thirdly, the mechanism of the
      health disorder and the reason why there seems to be a large inter-individual
      difference in sensitivity to the causative agent should be clarified.

PMID- 11993232
TI  - [Employee assistance program].
AB  - Recently the EAP has received much attention in Japan. The first EAP service in
      the US was conducted by employees who had recovered from alcohol problems. In the
      early days EAP providers focused on addiction, but mainly after 1980 they
      expanded their service areas to include mental health, marital problems, legal
      problems and financial problems. In Japan the EAP was first received attention as
      a counseling resource outside the workplace where employees could seek
      professional help confidentially, but the main reasons why this system now
      interests employers are as a risk-management tool and an outsourcing of mental
      health services, since the growing number of mental health cases in the workplace
      has been a big issue for employers. Two movements have also contributed to more
      recognition of the EAP: one is guidelines on compensation for mental health cases
      in the workplace and the other is guidelines on mental health promotion in the
      workplace. There are four types of EAP systems: internal EAP, external EAP,
      combination EAP, and consortium EAP. EAP core technology consists of 8 functions
      including problem identification, Crisis intervention, Short-term intervention,
      Consultation with work organization leader. The literature on cost-benefit
      analysis of the EAP is very limited. Although the available data suggest that the
      EAP is highly cost-effective, further studies are needed with the sufficient
      statistical quality. In Japan the most important issues in the EAP are the
      standardization and quality assurance of EAP services. For this purpose
      development of a good educational system for EAP professionals is needed.

PMID- 11993233
TI  - [The airborne 1,3-butadiene concentrations in rubber and plastic processing
      plants].
AB  - Environment pollution by 1,3-butadiene had considerably increased in Japan. The
      main cause of the pollution is the automotive exhaust gas, and leaks from
      factories, smoking, and burning of rubber and plastic products are considered to
      be minor sources. The object of this study was to determine the contamination
      levels of airborne 1,3-butadiene in factories processing rubber and plastics
      containing 1,3-butadiene. The concentrations of airborne 1,3-butadiene were
      measured in 21 plants (10 rubber processing plants and 11 plastics processing
      plants) in Osaka. 1,3-Butadiene in air was collected for 10 minutes with a
      charcoal tube and a portable small pump adjusted to a 250 ml/min flow rate. In
      each plant, indoor air samples at five points and an outdoor air sample at one
      point outside the plant were collected. The samples were subjected to gas
      chromatography/mass spectrometry after thermal desorption from the charcoal. The
      concentrations of airborne 1,3-butadiene in the rubber processing plants and the
      plastics processing plants were 0.14-2.20 micrograms/m3 (geometric mean: 0.48
      microgram/m3) and 0.23-4.51 micrograms/m3 (geometric mean: 0.80 microgram/m3),
      respectively. In all plants examined, indoor 1,3-butadiene concentrations were
      higher than the outdoor concentrations around the plants. Therefore, 1,3
      butadiene was considered to arise from the processing of rubber or plastics, but
      the indoor 1,3-butadiene concentrations were much lower than the PEL-TWA (1 ppm =
      2.21 mg/m3) of OSHA and the TLV-TWA (2 ppm) of ACGIH. The concentrations in the
      plants with closed room conditions without ventilation were higher than the
      concentrations in the other plants. It was suggested that ventilation affected
      the 1,3-butadiene concentration in the plants.

PMID- 11993234
TI  - [Trends in research and prevention policies for work-related musculoskeletal
      disorders at the European Agency for Safety and Health at Work (EU-OSHA)].
AB  - The European Agency for Safety and Health at Work (EU-OSHA) has been working on
      matters related to occupational health problems in 15 European Union (EU) member
      states. EU-OSHA established 10 topic centers on work and health research in 1998.
      One of the topic centers is assigned for research and information on work-related
      musculoskeletal disorders. The present report is written because such activities
      of EU-OSHA are scarcely known in Japan. Work-related musculoskeletal disorders
      have become a very serious problem in EU member states, i.e., 30% of workers
      complain of backache, and 17% complain of muscular pains in their arms and legs.
      The affected workers not only suffer at work but also in their home life. The
      economic costs of all work-related ill health range from 2.6 to 3.8% of the gross
      national product, and work-related musculoskeletal disorders constitute 40-50% of
      this. Therefore EU member states consider that prevention of work-related
      musculoskeletal disorders in itself is an extremely good economic policy. EU-OSHA
      published "Work-related neck and upper limb musculoskeletal disorders" in 1999,
      and "Research on work-related low back disorders" in 2000. These publications
      suggest various preventive methods which can be introduced in practice at work.
      One of the most remarkable things in EU-OSHA's activities for work-related
      musculoskeletal disorders is that EU-OSHA has been trying hard to introduce the
      results of its research into real policies for EU member states by several means,
      i.e., held a seminar participated in by policy makers, representatives of trade
      unions, and researchers from EU member states, and sent seminar resolutions to
      politicians who are responsible for employment and social affairs. Finally the
      resolution has been adopted in a new social affairs policy by the EU parliament
      and will be put into force during 2002. Work-related musculoskeletal disorders
      will remain one of the most serious occupational problems in EU member states,
      and EU-OSHA will continue to pay close attention to it.

PMID- 11993235
TI  - [Anatomical books in the Early Meiji period--the first systematic anatomical
      textbook, manual of dissection in anatomy laboratory and histological textbook in
      Japan].

PMID- 11993236
TI  - [Efforts to obtain agreement from members of "Shiragiku" for medical research
      using body donation].

PMID- 11993237
TI  - [Ultrastructural changes of collagen fibrils in mouse dermal connective tissue
      after moxibustion treatment].
AB  - Morphological changes in mouse back skin, especially dermal connective tissue,
      were observed after moxibustion treatment. Various amounts of direct moxibustion
      and indirect moxibustion (column) were performed and the exact skin area was
      processed for light and electron microscopy. Just after treatment, epidermal cell
      layer was degenerated and increased amounts of mast cells were observed. Many
      unwinding collagen fibrils were prominent. Twenty-four hours after treatment, the
      number of unwinding fibrils decreased. Instead, tightly winding fibrils,
      sometimes thicker, were observed in a similar area. D-period of collagen fibrils
      did not change in any situation. Physical reaction to moxibustion varies
      depending on stimulation rate and/or approach, which includes the change of
      interstitial connective tissues as well as cellular profiles. It is also
      important to survey the time-dependent changes in moxibustion treatment.

PMID- 11993238
TI  - Genetic mutation as a cause of male infertility in two brothers.
AB  - At the University of Iowa Hospitals and Clinics, two brothers seeking evaluation
      for male-factor infertility were discovered to carry the identical cystic
      fibrosis gene mutation. Neither brother had prior knowledge of the other
      brother's fertility problems.

PMID- 11993239
TI  - Validating methods of urine collection: a pilot study.
AB  - In this pilot study of 21 adults, direct collection versus cotton-ball collection
      of urine was studied. Results showed the use of cotton balls for collecting urine
      is a safe and effective method for measuring antioxidants and markers of
      oxidative stress for clinical and research use.

PMID- 11993240
TI  - Routine clean intermittent self-catheterization: innovative implementation in the
      Hunter Area Health Service.
AB  - Clean intermittent self-catheterization (CISC) has been used successfully for
      many years to promote socially acceptable and functional continence practice. The
      impact on health services, quality of life, and associated costs has also been
      documented. The use of CISC as a routine technique has been widely implemented in
      the Hunter Area Health Service, NSW, Australia. The positive outcomes resulting
      from the routine use of CISC has included reduction in length of stay and numbers
      of admissions for patients with urinary retention, reduction in nursing time, and
      decreased infection rates. The technique has been well received by patients who
      report a positive impact on their quality of life.

PMID- 11993241
TI  - The leadership of possibilities.

PMID- 11993242
TI  - Lessons learned: adult urine incontinence protective wear.

PMID- 11993243
TI  - BCG installations for bladder cancer and latent tuberculosis infection.

PMID- 11993244
TI  - Managing nursing care in the face of change.

PMID- 11993245
TI  - Penile prosthesis: patient teaching and perioperative care.
AB  - As more options become available for treating erectile dysfunction (ED), more men
      are seeking treatment. Despite excellent efficacy of available medical
      management, a percentage of these patients will be refractory to the less
      invasive options for treatment, leaving the surgical implantation of a penile
      prosthesis as their remaining option for definitive treatment of ED. The patient
      seeking penile prosthesis surgery faces many challenges as he proceeds through
      the perioperative processes. A thorough understanding of indications,
      preoperative assessment and teaching, intraoperative procedure, and postoperative
      care and teaching for the patient receiving a penile prosthesis will enable him
      to achieve the best possible outcome.

PMID- 11993246
TI  - Penile prosthesis case study.

PMID- 11993247
TI  - DHT levels.

PMID- 11993248
TI  - Rules to follow before advising patients on dietary supplements/alternative
      medicine: Part I.
AB  - Sales and the overall prevalence of dietary supplements/alternative medicine
      (CAM) use have dramatically increased in the United States and in numerous
      countries around the world. Thus, health care professionals should be provided
      with general rules to follow or guidelines on dietary supplements in order to
      improve communication with patients. In Part I of this series, ten rules that can
      be generally applied or used in a clinical setting will be described. Rules to
      follow when patients inquire about CAM will be outlined in Part II.

PMID- 11993249
TI  - The multiple benefits associated with HIV drug-resistance mutation M184V.

PMID- 11993250
TI  - New applications of contemporary biomarkers of alcohol consumption.

PMID- 11993251
TI  - Integrating laboratory services. The Rapid Response Laboratory (RRL) and Core
      Laboratory: a case study.

PMID- 11993252
TI  - Improved laboratory efficiency through cooperation, consultation, and
      consolidation.

PMID- 11993253
TI  - HIV infection, risk factors, and testing in a veteran population.

PMID- 11993254
TI  - Disclosure patterns among HIV+ women.

PMID- 11993255
TI  - Hepatitis B virus vaccine: cost effects and insurance coverage.

PMID- 11993256
TI  - Lab-on-a-chip-based separation and detection technology for clinical diagnostics.

PMID- 11993257
TI  - Needs of frail elderly people in informal settlements.
AB  - The frail elderly in informal settlements find themselves in an extremely
      vulnerable position due to a number of factors, namely, their increasing
      dependency status, limited resources and adverse physical environment. Various
      aspects that influence the aged in their present environment will be highlighted.
      A survey method was used to explore and to describe the world in which they live
      in informal areas. The attitude, expectation and needs of the elderly in respect
      of their care was also determined. A random cluster sample was taken. Data was
      collected by means of interviews in terms of a semi-structured questionnaire. It
      appears that the frail elderly were happy in the environment in which they
      received care in spite of their unfavourable physical environment and limited
      resources. The communities where the frail elderly lived were largely unaware of
      the valuable inputs they can make regarding the care of the aged. This
      necessitates the development of programs in the heart of communities, owned by
      communities, where all role players in the care of the aged participate.

PMID- 11993258
TI  - Enabling legislation in diagnosis and prescribing of medicine by nurses/health
      practitioners.
AB  - The South African health system has undergone major changes over the last 5-10
      years. These rapid changes have not only significantly increased the visibility
      of the nurse practitioner in South Africa, but are also posing challenges to the
      profession and health care services that need to be addressed. In its Health
      Policies the Government has indicated that the nursing/midwifery profession, as
      the biggest group of health care professionals, should be the practitioners to
      provide primary health care services to the communities. But to do this, they
      require enabling legislation. The "permit system" has been in place for non
      pharmacists and institutions other than hospitals and pharmacies to acquire,
      possess, use and supply medication for a number of years. This system has been
      fraught with problems mainly due to a lack of clarity on exactly how the system
      works and the system had been abused. The purpose of this article is to explore
      the current situation with the aim to analyze the legal framework that exists
      within which the primary health care services, and specifically the diagnosing
      and prescribing of medication, could be performed. The conclusion is made that
      health legislation has not kept up with the rapid changes in service delivery and
      are not adequate to empower the nurse to deliver health services. Some
      recommendations are made for the way forward.

PMID- 11993259
TI  - Abortion--a philosophical perspective.
AB  - The central issue in the abortion debate is the moral status of the conceptus.
      There are two positions that argue this issue. At one extreme are the views of
      the pro-life group which argues that human life begins at the moment of
      conception whilst at the other are views of the pro-choice group that argues in
      favour of a woman's right to self-determination. Two basic principles come into
      conflict in this debate, namely the Value of Life and that of Self-determination.
      In this paper the arguments forwarded by each group in justification of its
      position are presented. Also discussed is the moderate developmental viewpoint
      which accepts that the genetic basis of an individual is established at
      conception. Some development, however, has to occur before the conceptus can be
      called a person. The fact that an entity is a potential person is a prima facie
      reason for not destroying it. On the other hand, we need not conclude that a
      person has a right to life by virtue of that potentiality. Simultaneously we
      should recognise that the right a potential entity has, may be nullified by the
      woman's right to self-determination.

PMID- 11993260
TI  - The adoption of technology in higher/nursing education.
AB  - This is a review article on the adoption of technology in higher education.
      Higher education in general is looked at. Nursing Education is also higher
      education and therefore it will not be addressed separately, but mentioned in
      some instances. The article presents a look into how students and lecturers
      experience change, as well as barriers they perceive in the integration and
      adoption of technology. Some suggestions are made to the adoption process as well
      as the necessity for personnel development in information technology. The role
      that Information Technology personnel play in the adoption and integration
      process of technology is also discussed.

PMID- 11993261
TI  - Strike action by nurses in South Africa: a value clarification.
AB  - The Labour Relations Act (South Africa, 1991) made provision for protected strike
      action by employees, subject to certain conditions, procedures and negotiated
      agreements. This led to the removal of the strike clause in the Nursing Act
      (South Africa, 1992). The labour rights of all citizens are entrenched in the
      Constitution of the country (South Africa, 1996). Participation in strike action
      by the nurse/midwife, regardless of the legal requirements and specifications,
      does, however, pose an ethical question. It is therefore necessary to conduct a
      value clarification on strike action by nurses in South Africa. The purpose of
      this research is to explore and describe the perceived values of participants
      from an accessible population on this phenomenon. A qualitative, exploratory and
      descriptive research design was deployed. The perceived values of nurses on
      strike action were collected by means of an open-ended questionnaire/sketch. Over
      a period of three years a purposive and convenient sampling method was used,
      involving all the enrolled post basic nursing/midwifery students/learners at a
      particular Nursing Education Institution. The justification of the sample was
      further enhanced by also collecting data on the participants' age and provincial
      distribution location. Although a 63% sample realisation (of the accessible
      population) was achieved, this represents only 1.5% of the registered
      nursing/midwifery population in the country. A descriptive analysis of the
      participants' age and provincial distribution was undertaken, as well as a
      content analysis of their perceived values on strike action. The mean age of the
      participants was 48 years, which could be attributed to the fact that most of
      them were enrolled for a post-basic Diploma in Community Nursing Science. Most of
      the responses (52.7%) were against strike action and 32.5% supported strike
      action by nurses as a constitutional and legal right. A fairly substantial number
      of participants (14.8%) expressed mixed views as to whether strike action by
      nurses is right or wrong. Some respondents (15.7%) also reflected confusion
      regarding the enactment of strike action and the removal of the strike clause
      from the nursing legislation. Although this study does not claim external
      validity due to inappropriate representation of the nursing profession, the nurse
      of today opposes strike action. It is recommended that the study be replicated at
      national level and that the values be entrenched and published in position papers
      of and by the regulatory and organised nursing profession.

PMID- 11993262
TI  - Theory-practice integration in selected clinical situations.
AB  - The current changes in health care systems challenge knowledgeable, mature and
      independent practitioners to integrate theoretical content with practice. The aim
      of this study was to investigate the problems of integrating theory with practice
      in selected clinical nursing situations. The study focused on rendering of family
      planning services to clients as a component of Community Nursing Science.
      Structured observation schedules were used to observe the theoretical content of
      the curriculum as well as the practical application of what has been taught in
      the clinical area. The findings of the study revealed that there was a need for
      an integrated holistic curriculum, which would address the needs of the
      community. It was concluded that a problem-based and community-based curriculum,
      intersectoral collaboration between college and hospital managements and student
      involvement in all processes of teaching and learning would improve the
      integration of theory and practice. There also appeared to be a need for tutors
      to be more involved in clinical teaching and accompaniment.

PMID- 11993263
TI  - Knowledge and attitudes of primary care nurses and midwives towards health
      promotion in rural South Africa.
AB  - This study was designed to study knowledge, attitudes and views about health
      promotion among nurse clinicians in rural South Africa. The sample included 90
      nurse clinicians (73 primary health care nurses and 17 midwives) in the age range
      of 24 to 59 years (M age 38.4 yr., SD = 9.3) in the Northern Province. Results
      indicate that nurses (66.6%) had an inadequate knowledge score on health
      promotion in this sample. Higher knowledge scores on health promotion were not
      associated with age and years of experience. However, male nurses had
      significantly higher knowledge scores on health promotion than female nurses. The
      majority strongly supported the centrality of their role in health promotion
      acknowledging the time constraints involved. Better knowledge on health promotion
      was associated with more positive views on health promotion. More nurses had a
      satisfactory positive attitude towards health promotion (63.3%) than knowledge
      about health promotion (33.3%). Finally, the study found that compliance with
      health promotion was seen as a problem but health counselling was nevertheless
      seen as cost effective.

PMID- 11993264
TI  - Employees' perceptions of the implementation of affirmative action in the health
      sector in the Standerton District in South Africa.
AB  - Since the inception of a fully democratic government in South Africa in 1994,
      government and trade unions have been placing increasing pressure on government
      departments and public institutions to introduce steps to correct racial
      discrimination through the implementation of affirmative action (AA). This study,
      which was carried out in the Standerton Health District, assesses employees'
      perceptions of and attitudes towards the implementation of AA. A quantitative
      design was used. Data was gathered from a total population of 360 employees by
      means of a questionnaire. The study revealed the following major themes:
      Respondents feel that if AA were effectively implemented, there would be an
      increase in productivity. There is strong support for the implementation of AA
      appointments. The implementation of AA will fail if the goals of AA are not
      properly and effectively communicated to all employees.

PMID- 11993265
TI  - The role of the community nurse on health committees.
AB  - With the changes in health care occurring in South Africa, new functions
      concerning the community nurse are being presented. The goal of the study was to
      explore and describe the role of the community nurse in health committees. An
      explorative, descriptive design was used and the empirical part was undertaken
      within the context of a metropolitan local authority. After conducting a
      literature study, six major roles of the community nurse on health committees
      were identified. After that a questionnaire was presented to community nurses to
      explore and describe their perceptions about the role of the community nurse on
      health committees. An interview schedule based on the literature study was
      drafted for presentation to selected members of health committees. Lastly
      guidelines describing the role of the community nurse on health committees were
      developed based on the findings of the study.

PMID- 11993266
TI  - Application and evaluation of a combination of socratice and learning through
      discussion techniques.
AB  - This article has its genesis in the inquirer's interest in the need for
      internalizing critical thinking, creative thinking and reflective skills in adult
      learners. As part of a broader study the inquirer used a combination of two
      techniques over a period of nine months, namely: Socratic discussion/questioning
      and Learning Through Discussion Technique. The inquirer within this inquiry
      elected mainly qualitative methods, because they were seen as more adaptable to
      dealing with multiple realities and more sensitive and adaptable to the many
      shaping influences and value patterns that may be encountered (Lincoln & Guba,
      1989). Purposive sampling was used and sample size (n = 10) was determined by the
      willingness of potential participants to enlist in the chosen techniques.
      Feedback from participants was obtained: (1) verbally after each discussion
      session, and (2) in written format after completion of the course content. The
      final/summative evaluation was obtained through a semi-structured questionnaire.
      This was deemed necessary, in that the participants were already studying for the
      end of the year examination. For the purpose of this condensed report the
      inquirer reflected only on the feedback obtained with the help of the
      questionnaire. The empirical study showed that in spite of various adaptation
      problems experienced, eight (8) of the ten (10) participants felt positive toward
      the applied techniques.

PMID- 11993267
TI  - On lead(II) glycocholate solubility.
AB  - The solubility of lead(II) glycocholate was studied as a function of glycocholate
      ion concentration at 25 degrees C and in 0.100, 0.500 and 0.800 mol dm-3
      N(CH3)4Cl as a constant ionic medium. For this purpose the total concentration of
      lead(II) was determined by means of atomic absorption spectrophotometry and
      polarography measurements in solution equilibrated with solid lead(II)
      glycocholate at known hydrogen ion concentration. The free concentration of
      lead(II) and hydrogen ions was determined by measuring the electromotive
      force(e.m.f.) of galvanic cells involving lead amalgam and glass electrode. The
      e.m.f. measurements were carried out both in clear solutions before precipitation
      and in the presence of the precipitate. The results of the solubility and e.m.f.
      measurements could be explained by assuming the presence of associated species
      between lead(II) and glycocholate. The solubility product and the association
      constants were determined for all the ionic medium concentrations.

PMID- 11993268
TI  - Thermal behaviour of 6-(2-pyridylazo)-3-acetamidophenol and its metal complexes.
AB  - The present work aims chiefly to study the thermal behaviour of Fe(III), Co(II),
      Ni(II), Cu(II), Zn(II) and Cd(II) complexes with 6-(2-pyridylazo)-3
      acetamidophenol (PAAP) in nitrogen atmosphere. The moieties of the prepared
      complexes contain mainly coordinated water molecules (1-3) together with some
      water of crystallization. The water molecules of crystallization are removed in a
      single stage. The decomposition and combustion of the fragments occur in the
      second and subsequent stages. The fragmentation of the prepared complexes is also
      studied by mass spectrometry in order to identify the molecular ions obtained.
      The comparison of thermal analysis (TG) and mass spectra of the compounds is
      helpful in checking the correct proposed thermal decomposition schemes. This
      comparative study shows that mass spectra are correlated with the thermal
      analyses suggestions. The activation thermodynamic parameters of thermal
      decomposition pathways, such as energy of activation, enthalpy, entropy and free
      energy change of the complexes are evaluated and the stability of the thermal
      treated complexes is discussed, which shows that the thermal stabilities of the
      complexes are enhanced as the ionic radii decrease.

PMID- 11993269
TI  - A new sensitive method for the spectrophotometric determination of molybdenum
      using 3-hydroxy-2-(2'-thienyl)-4H-chromen-4-one.
AB  - A spectrophotometric method has been developed for the determination of
      Molybdenum (VI) using 3-hydroxy-2-(2'-thienyl)-4H-chromen-4-one as a complexing
      agent. The complex formed was dissolved in water in the presence of Triton X-100
      and exhibits an absorption maximum at 410 nm. A large number of metal ions like
      Co(II), Ni(II), Mn(II), Cr(III), Zn(II), Cu(II), Hg(II), Bi(III), Fe(II),
      Fe(III), Zr(IV), V(V) can be tolerated at an appreciable concentrations. Molar
      absorptivity and Sandell's sensitivity of the method is 2.80 x 10(5) l mol-1cm-1
      and 3.42 x 10(-4) micrograms cm-2, respectively. Beer's law is obeyed in the
      concentration range of 0.01-0.4 ppm Mo(VI). Aliquots containing 0.2 ppm of Mo(VI)
      give a mean absorbance of 0.56 with a relative standard deviation of 1.3%.

PMID- 11993270
TI  - Dapsone a new diazotizing reagent for the spectrophotometric determination of
      nitrite in waste and natural water samples.
AB  - A new diazotizing reagent for the spectrophotometric determination of nitrite is
      described. The method is based on diazotization-coupling reaction between dapsone
      and phloroglucinol in hydrochloric acid medium. The reactions were conducted at
      room temperature, the molor absorptivity at 425 nm is 4.28 x 10(4) l mol-1cm-1
      and was stable for 50 h. Beer's law was obeyed in the nitrite range of 0.008-1.0
      microgram ml-1. Tolerance limits were tested for 33 species. The method has been
      found to be applicable for the determination of nitrite in natural and
      wastewater.

PMID- 11993271
TI  - Measurement of total body water (TBW) through in vivo dilution of tracer
      compounds: use of D2O and its determination by FT infrared spectroscopy.

PMID- 11993272
TI  - Complexometric determination of thallium (III) in low concentrations using oxalic
      acid as releasing agent.

PMID- 11993273
TI  - Aerobic biotransformation of linear alkylbenzene sulphonates under laboratory
      conditions.
AB  - Sulphophenyl carboxylates (SPC) derived from the biodegradation of commercial
      blends of linear alkylbenzene sulphonates (LAS), were recorded during OECD-301E
      screening tests under aerobic conditions. Both HPLC-FL and GC-MS were employed to
      determine biotransformation products. Two well defined groups of detectable SPC
      were generated: transient compounds, i.e. SPC which degrade very quickly, and
      compounds more persistent than the parent LAS which required an acclimatization
      period before their mineralization could take place. The biodegradation of a C10
      C13 LAS commercial mixture and of two individual homologs (C11-LAS and C12-LAS)
      led to the identification of the most persistent SPC which were C6-SPC, C7-SPC
      and C8-SPC. The C6-SPC turned out to be the homolog which biodegrades most
      slowly, this suggests that odd LAS homologs are more easily biodegradable.

PMID- 11993274
TI  - UV and H2O2/UV degradation of a pharmaceutical intermediate in aqueous solution.
AB  - The degradation of 5-methyl-1,3,4-thiadiazole-2-thiol (MMTD), a pharmaceutical
      intermediate found in some aquifers of Northern Italy, has been investigated by
      means of UV and UV/H2O2 treatments. The study has been carried out with a 17 W
      low pressure mercury lamp at room temperature, using a (100)/(1) (H2O2)/(MMTD)
      molar ratio. The results have demonstrated that: (i) with an initial MMTD
      concentration of 1 mg/l, 90% MMTD removal can be achieved within 1 hour or less
      than 5 minutes by UV or UV/H2O2 respectively; (ii) the sole UV irradiation does
      not cause any MMTD mineralization; (iii) with an initial MMTD concentration of 50
      mg/l, 4 hours of UV/H2O2 treatment lead to an almost complete mineralization of
      the MMTD organic sulfur and to a partial mineralization of carbon (59%) and
      nitrogen (14%). The identification of degradation by-products, performed by HPLC
      UV-MS analysis, revealed that the sole UV irradiation gives rise to the MMTD
      transformation into a single by-product that continuously accumulates in the
      solution. Conversely, the UV/H2O2 treatment forms seven intermediates that
      undergo further degradation through the breakdown of the thiadiazole ring. On the
      basis of the obtained results a degradation pathway has been proposed.

PMID- 11993275
TI  - Optimization of cyanide elimination from an industrial wastewater on a pilot
      plant scale.
AB  - A pilot plant scale reactor was modelled and assembled to experimentally study
      the cyanide elimination process. The process was performed by using Ca(OCl)2, Cl2
      and H2O2. The elimination was optimized at 25 degrees C for time of reaction, pH
      and amount of oxidant in a pilot plant scale reactor with synthetic solutions.
      Moreover some tests were carried out by using a real effluent deriving from a
      gold production industry.

PMID- 11993276
TI  - Time trends of 1,1,1-trichloroethane, trichloroethylene, and perchloroethylene in
      confined and unconfined aquifers of a groundwater system in northern Italy.
AB  - The concentrations of 1,1,1-trichloroethane, trichloroethylene, and
      perchloroethylene were recorded in a groundwater system of Northern Italy over
      the period 1985-1997. In the unconfined recharging aquifer these chemicals showed
      a remarkable overall decline which was accompanied by a five-fold reduction in
      their consumption (from approx. 250 to approx. 50 tons year-1) over the same
      period. The time trends for the confined aquifers indicated a steady decline for
      1,1,1-trichloroethane which was accompanied by a constant concentration of
      trichloroethylene and an increasing presence of perchloroethylene. It is
      suggested that the confined aquifers are recording a contamination which took
      place in the unconfined recharging aquifer before monitoring period (1982)
      started. At present, in most of the study area 1,1,1-trichloroethane
      contamination is below the detection limit (0.1 microgram/L). For
      trichloroethylene and perchloroethylene, the average unconfined aquifer
      contamination accounts for approx. 1 +/- 1 and approx. 4 +/- 3 micrograms/L,
      respectively, while in the confined aquifers the average concentrations are
      approx. 8 +/- 3 and approx. 35 +/- 5 micrograms/L, respectively.

PMID- 11993277
TI  - 226RA analysis in sea and river water by adsorption on specific adsorbers.
AB  - A method to analyse 226Ra in sea water Ra in sea water was investigated. The
      chemical procedure is based on adsorption of radium and barium, used as a
      carrier, on the specific adsorber PRTD at pH 9.5. The main interference is due to
      magnesium. The magnesium concentration is depleted by precipitating barium
      (carrier) and radium with calcium carbonate at pH 8 before the adsorption step.
      The proposed chemical procedure is simple and easily performed. The overall
      chemical yield is evaluated on the basis of the 133Ba spike. The sensitivity of
      the method is related to the volume of sea water. Under the experimental
      conditions used, 5 L of sea water, the limit was 1 226Ra mBq/L of water. The
      method may be also applied to the analysis of radium in river water, by omitting
      the carbonate precipitation.

PMID- 11993278
TI  - Number of eggs in egg-noodles.
AB  - The official method to determine the number of eggs present in egg-noodles is the
      digitonin method. By applying this method the total content of sterols is
      determined and expressed as total sterols. The official method is time consuming,
      not very accurate and its performance is very complicated. Its results are not
      very reliable either because the composition of the wheat is not considered. In
      this paper some markers are proposed to verify the correct ratio between eggs and
      triticum durum (TD) semolina used to prepare egg-noodles. Markers are selected
      ratios between sterols and FAME. The lipid extract is trans-esterified and
      injected into a gas chromatograph. The ratio between the areas of the selected
      components gives the markers. This method is proposed to substitute or alternate
      the official method because is more accurate and time saving.

PMID- 11993279
TI  - Validation of different commercially available cholinesterases for pesticide
      toxicity test.
AB  - A systematic study of different commercially available cholinesterases (AChEs
      from electric eel, human erythrocytes, bovine erythrocytes and BuChE from horse
      serum) for the FIA determination of some frequently used organophosphate
      (paraoxon, oxydemeton-methyl, triazophos, diazionon) and carbamate (carbofuran,
      propoxur) pesticides was carried out. Responses of the previously developed
      photothermal FIA system were found to be dependent on the origin of
      cholinesterases and properties of tested pesticides. The highest sensitivity was
      obtained with electric eel AChE and the lowest sensitivity with horse serum
      BuChE. The LOD values for investigated pesticides correlate with acute toxicities
      expressed as LD50 (oral, rat). The presented FIA system could serve as an
      alternative screening test to evaluate the toxicity of different environmental
      samples, new cholinesterase inhibiting pesticides or other products (e.g. nerve
      gases).

PMID- 11993280
TI  - Addiction medicine.

PMID- 11993281
TI  - Risk factors for substance abuse in adolescents.
AB  - Much is written of adolescents taking risks, including using drugs and alcohol,
      without a clear understanding of factors that promote or deter such behaviors.
      This article attempts to clarify these factors in order to help physicians
      understand why adolescents behave in these ways and to help physicians develop
      methods to prevent these risky behaviors.

PMID- 11993282
TI  - Prevention and risk of adolescent substance abuse. The role of adolescents,
      families, and communities.
AB  - Adolescents as young as 12 to 14 years of age are engaging in substance use [16].
      Those who use substances are at risk for immediate and future consequences that
      affect morbidity and mortality. The theoretical models of substance use in
      adolescents provide a framework for understanding risk and protective factors.
      These risk and protective factors are pertinent to all contexts, including the
      individual traits, interpersonal relationships, and greater society. Knowledge of
      these factors should help the clinician in assessment of the individual
      adolescent. Knowledge of these factors also should help the clinician provide
      appropriate interventions. In the case of primary prevention, clinicians can
      advocate for families and communities to teach children how to be more goal
      oriented, insightful, and in tune with their cultures and beliefs. Parents also
      can be encouraged to set clear limits, monitor their adolescents' behaviors, be
      good role models, and provide a loving and supportive environment. Advocacy to
      address some of the societal factors that are less easily changed also has its
      place. Addressing media portrayal of drug use, availability of substances, and
      poverty would have a broad impact on the problem of adolescent substance use and
      would help to improve the health status of many adolescents in the United States.

PMID- 11993283
TI  - Adolescent substance abuse. Assessment in the office.
AB  - There are no gold-standard tests for evaluating a teen suspected of abusing
      substances. Awareness of the high prevalence of substance abuse in youth, a high
      index of suspicion, and a firm desire to be a part of the solution are all that
      is required to address the problem of substance abuse in youth. In an age of
      "dotcoms" and societal complexity that fosters an emotionally "disconnected"
      atmosphere by uniting adolescents only by what they buy, plug into, click on, or
      blast away, teens need trusted medical homes where caring pediatricians are
      available to give youth accurate and authoritative facts and care to help them
      build inner resilience and connect them to the pain and hurt of the people in
      their lives. Until now, the "three strikes and you're out" maxim has been applied
      in medical care. This maxim may work for baseball, Clintonomics, and practical
      office management strategies but is not recommended for addressing the needs of
      substance using or abusing youth who are prey to advertising strategies. The size
      of the marketing and advertising budgets of the alcohol and cigarette industries
      is an indication of the relentless marketing directed toward vulnerable youth.
      Pediatricians would be doing teens a disservice if they fail to countermand this
      marketing effect by not using the "rule of seven"--the "seven 'S' screen," seven
      education attempts, seven different ways over 7 years, and persistence over seven
      attempts of chemically dependent adolescents to quit. It has been said by Osler
      that "These are our methods--to carefully observe the phenomena of life in all
      its stages, to cultivate the reasoning of the faculty so as to be able to know
      the true from the false. This is our work--to prevent disease, to relieve
      suffering, to heal the sick," and provide HOPE always.

PMID- 11993284
TI  - Adolescent substance abuse. Confidentiality and consent.
AB  - Although all states have laws that allow minors to consent to substance abuse
      treatment, there is variability from state to state. Health care providers need
      to be aware of laws within their states. When providing health care to
      adolescents, many situations arise in which the provider must make a
      determination of the patient's competence to consent and whether parental
      notification would be in the patient's best interest. Confidentiality should be
      honored when possible, with limitations of the extent of confidentiality
      explained. Adolescents are able to consent for alcohol and drug treatment in most
      states, but involvement of the family is optimal in most cases. Physicians and
      other medical care providers also need to manage confidentiality issues in drug
      testing, billing of services, and medical records and need to work with clinical
      administrative staff to clarify and implement policies to maintain
      confidentiality. Proposed changes to medical privacy regulations may compromise
      confidentiality for medical care of adolescents. Medical providers should
      continue to work with their professional societies and legislators to ensure that
      appropriate consent and confidentiality statues exist to provide optimal health
      care to adolescents.

PMID- 11993285
TI  - Urine drug screening in adolescents.
AB  - The urine drug screen is an important tool in adolescent medicine. Several
      ethical, and numerous technical, issues are associated with the use of this tool.
      The nature and limitations of the specific tests of which the screen is composed
      must be known to the physician. Two-way communication with the laboratory, both
      before the test is ordered and after the results are reported, can be very
      helpful. Laboratory testing cannot substitute for an ongoing therapeutic alliance
      with the patient. Testing is an important element of the substance use
      assessment, but is only one element, is not required in every case, and is not
      sufficient alone in any case.

PMID- 11993286
TI  - Office-based intervention for adolescent substance abuse.
AB  - Because substance use is highly prevalent among teens, primary care clinicians
      may not be able to refer all adolescents to drug counselors or mental health care
      professionals. Pediatricians may therefore find it useful to use the basic
      principles of office intervention and reserve referral for those patients with
      the most significant drug and alcohol problems. Brief interventions have proven
      effective in reducing problematic drinking among adults, and early work among
      adolescents is promising. Effective interventions include feedback on risks and
      problems, an emphasis on personal responsibility, a menu of alternatives for
      change, an empathetic approach, and reinforcement of patient self-efficacy.
      Motivational interviewing is an effective means of enhancing success in
      counseling. When a referral is necessary, motivational interviewing can be used
      to maximize adherence.

PMID- 11993287
TI  - Treatment and relapse prevention for adolescent substance abuse.
AB  - Treatment of adolescent substance use varies with the stage of involvement.
      Treatment of Substance Abuse or Dependency Disorder involves family treatments,
      cognitive behavioral techniques, motivation interviewing and 12-step approaches.
      The most common pathway to relapse involves being around alcohol/drug using
      peers.

PMID- 11993288
TI  - Alcohol advertising and adolescents.
AB  - Considerable research now exists that the media may exert a powerful influence on
      adolescents' drug-taking behavior. Teens view an average of 2,000 beer and wine
      ads per year in the US. In addition, television shows, movies, and music videos
      contain considerable amounts of alcohol use. This article will discuss the
      available research and offers suggestions to make the media healthier for
      teenagers.

PMID- 11993289
TI  - Reducing tobacco use among youth.
AB  - Reducing tobacco use among young people is an important challenge as we head into
      the twenty-first century. Old strategies have gone away as new ones have emerged.
      Old research and opinion-based approaches are being replaced by data-driven,
      analyzable programs. One thing that clearly has not changed is the importance of
      prevention and education. Another is the need for pediatricians and all those who
      care about children to address the issue of tobacco's toll early and often.

PMID- 11993290
TI  - Marijuana use among adolescents.
AB  - More than half of US adolescents will experiment with marijuana. Of those who try
      marijuana more than once, approximately one third will subsequently use marijuana
      regularly, although most will have stopped by their late 20s. Although genetic
      predisposition plays the most important role in determining who will develop
      dependence, environmental factors influence who will initiate marijuana use. One
      of the challenges for prevention and treatment programs is that the immediate
      adverse effects of marijuana use are not extreme, and many adolescents have
      difficulty in making decisions based on future risks. Therefore, the consequences
      of leaving school early, having unprotected sex, and driving while intoxicated
      are often insufficient to deter adolescents from using marijuana. Thus, it is not
      surprising that current prevention and treatment programs have had limited
      success in decreasing the rates of initiation and regular use of marijuana among
      adolescents. However, the accumulation of data about marijuana use in adolescents
      has the potential to enable the development of more effective prevention and
      treatment programs.

PMID- 11993291
TI  - MDMA ('ecstasy') and other 'club drugs'. The new epidemic.
AB  - Unfortunately, perceptions that the club drugs can be safe endure. Some groups,
      such as the Multidisciplinary Association for Psychedelic Study, continue to
      lobby for the legalization of MDMA for research purposes [76]. DanceSafe is an
      organization that seeks to educate the "nonaddicted" user to decrease the risks
      [82]. The DanceSafe Web site offers tips on the safe use of MDMA, such as
      attention to hydration status and ambient temperature. It also offers free
      testing of tablets submitted by mail and sells home testing kits to determine the
      content of pills sold as "ecstasy." Although much remains unknown about the long
      term consequences of MDMA and the club drugs, there are clearly enough short-term
      dangers to prompt more aggressive education and surveillance for its use. Scare
      tactics and exaggerations often are ignored [53], while Web sites full of
      anecdotal or incomplete information may lead the unaware user to increased use
      [113]. Organizations such as DanceSafe imply that proper education decreases
      addiction and that only uneducated users or addicts suffer the life-altering
      consequences of drug use. The fallacy in the mission of educating "nonaddicted"
      users is evident. Peer-based education, with a focus on both he short-term
      dangers and long-term consequences, may be a more effective approach [9]. Both
      new and established drugs of abuse continue to plague teens and young adults.
      Pediatric, family practice, and Med-Peds physicians, and pediatric
      pharmacologists need to remain vigilant about patterns and trends of drug abuse.
      MDMA and the other "club drugs" are not benign. Their effects target the brain,
      alter neurochemistry, and possibly cause irreversible structural damage. What may
      seem like a harmless drug in a weekend dance club has the potential for major
      public health problems in years to come [109]. Effective education and timely
      intervention may prevent these addictive drugs from becoming a way of life, a
      lifestyle that may have a literal "dead end."

PMID- 11993292
TI  - Supplements and drugs used to enhance athletic performance.
AB  - The temptation of using drugs and supplements as shortcuts to improving athletic
      performance or even to enhance appearance is very seductive to adolescents. This
      age group is often characterized by a desire for quick results and a lack of
      concern for future consequences. Preventing the use of drugs to enhance athletic
      performance is difficult even when we have good medical and scientific evidence
      to prove a dangerous risk-benefit ratio, such as with AASs. The use of
      "nutritional supplements" is even more difficult to control. The protection of
      these substances by the Dietary Supplement Health and Education Act of 1994
      removed control of these substances from the FDA. Therefore, release and
      widespread use of new supplements occurs before significant clinical study of
      benefit and adverse effects takes place. The distributors' financial interest,
      the products' promotional claims, and the athletes' and coaches' insatiable
      desire to win at all costs are a volatile combination. This spawns the production
      of a huge number of "natural" products, making it even more difficult to assess
      efficacy, safety, legality, and purity of these substances. Health care
      professionals need to rely on research when available, stay current on trends in
      athletes' drug and supplement use, and discuss the individual athlete's concerns
      when they arise. The preparticipation physical examination can be a good
      opportunity for discussion. Finally, physicians need to educate athletes,
      parents, coaches, trainers, and other physicians. A reasonable strength and
      conditioning program and a well-balanced diet must be presented as a sensible
      alternative to a riskier, shortcut mindset.

PMID- 11993293
TI  - Adolescent substance use disorders and comorbidity.
AB  - It is imperative to know what risk factors are more likely to appear during
      specific developmental stages so that identification and interventions can be
      used to decrease the risk for future SUD. Continued surveying of risk factors
      that can occur at any stage in childhood are important to ensure that other risk
      factors are anticipated and intervened upon as well. Multiple risk factors
      increase the magnitude of the risk for SUD, and therefore all risk factors should
      be detected to convert these to protective factors. Screening instruments that
      can assess risk factors found to increase the risk for substance abuse can be
      found in examples, such as the Drug Usage Screening Instrument [81] and the
      Problem-Oriented Screening Instrument for Teenagers. The detection of risk
      factors by primary care providers is becoming increasingly important. However,
      other professionals are beginning to recognize that early recognition and
      treatment can enable a youth to go on to a productive life in other arenas as
      well. Drug courts and diversion programs are beginning to treat first-time
      offenders and their families rather than taking the punitive approach. These have
      proven to be very successful. Primary care physicians also should become familiar
      with motivational enhancement therapy when confronting a youth with a suspected
      substance abuse problem [57]. This method has proven to be more effective in
      getting youth into treatment than the direct, confrontational style, which often
      puts the youth in a defensive mode. Motivational enhancement therapy includes
      interventions that are delivered in a neutral and empathetic way. The six
      components of motivational enhancement therapy (also called FRAMES) include:
      Feedback on personal impairment Emphasis on personal responsibility Clear advice
      to change Menu of alternative options Empathy as a counseling style Self-efficacy
      In this way, a clinician can elicit pros and cons, give advice, provide choices,
      practice empathy, clarify goals, and remove barriers. This technique allows youth
      to be less defensive and more proactive. Monti et al. [59] have demonstrated that
      this technique has been useful in getting youth into treatment. Primary care
      physicians can use instruments that will assess the possibility of both
      externalizing (e.g., ADHD) and internalizing (e.g., depression and anxiety)
      disorders. Examples of this type of instrument are the Auchenbach child behavior
      checklist, teacher report form, and youth self-report form, which survey symptoms
      for these disorders [1]. Social anxiety disorder can be detected by asking
      whether the prelatency child went into new situations willingly and tended to
      hang back or whether the child had difficulty separating from his or her parents.
      Other questions to ask are whether the child tended to isolate or was fearful of
      speaking in front of the class. Of course, any bruising or behavior that suggests
      exposure to adult-related sexual acts may cause concern for physical or sexual
      abuse and possible PTSD. However, interest in sex earlier than expected for the
      age of the child may also indicate the possibility of bipolar disorder. These
      children have many symptoms of ADHD with a high degree of irritability and may
      seem boastful or grandiose. They may be "daredevils" with no fear of dangerous
      consequences. Referral to a specialist is necessary to evaluate these children
      further. Because substance use at age 14 or 15 years can be predicted by academic
      and social behavior at ages 7 to 9 years, early detection of poor social skills
      and learning difficulties is essential [43]. Learning disorders can be uncovered
      by asking the school to do an evaluation. However, schools having economic
      problems may not be able to accommodate all requests. A parent may have to pay a
      private provider to complete this workup because insurance companies seldom pay
      for educational testing. Learning disorders may go undetected because many school
      systems opt to use a higher deviation from the full-scale IQ to detect learning
      problems. For instance, if a student has an IQ of 115, the standard nationally
      recommended deviation from this IQ to detect a learning disorder is 15.
      Therefore, any child who scores 100 or less on an achievement test should be
      considered to have a learning disorder. Some schools prefer to use a deviation of
      up to 23 so that learning disorders are not detected. Few schools screen for
      processing problems, including auditory and visual motor processing problems,
      processing speed, comprehension, and short-term and long-term memory problems.
      This is extremely important because ADHD can be confused with an auditory
      processing problem. Stimulants may help this condition, but accommodations must
      be made to ensure continued success. Early-intervention programs, such as Drug
      Abuse Resistance Education (DARE), proved to be ineffective because the programs
      did not target components that have been shown to predict future drug use [54].
      One program that has targeted these components, normative beliefs, lifestyle
      behavior incongruence, and commitment is the All Stars program [39,40]. A strong
      initial dosage with booster interventions for at least 2 years is also important
      [10]. Before a child is diagnosed with oppositional defiant disorder or conduct
      disorder, every effort should be made to detect any underlying psychiatric
      disorder that has not been treated and therefore may look like a conduct disorder
      (e.g., bipolar disorder). Proper psychopharmacologic interventions should be made
      for psychiatric disorders. If one drug has been ineffective, another untreated
      psychiatric disorder may be present, and it is always important to tease out what
      remaining symptoms are present after a therapeutic trial has been tried. It is
      important to form a team approach so that all risk factors can be approached.
      Members of the team often include a primary care physician, a child psychologist,
      the parents, the patient, a teacher, a school counselor, a child psychiatrist,
      and sometimes a pediatric neurologist. No one member of the treatment team can
      provide all of the necessary services to prevent the future risk for substance
      abuse.

PMID- 11993294
TI  - Eye protection--urban myth?

PMID- 11993296
TI  - Lifelong learning.

PMID- 11993295
TI  - Eye protection--a view from The Netherlands.

PMID- 11993297
TI  - The hazards of surgical smoke. Not to be sniffed at!
AB  - This article is based on a presentation given at Congress 2001 in Harrogate. It
      focuses on the risks to perioperative team members arising from the production of
      smoke during electrosurgical and laser procedures. It identifies the sources and
      nature of the risks, the failure of masks to provide adequate protection and
      suggests the standards that need to be set to reduce the risks.

PMID- 11993298
TI  - Fume levels during bone cement mixing.
AB  - This article compares some of the various products available for mixing and
      preparing bone cement. It should be noted that the tests were not independent as
      the author is employed by one of the product manufacturers. It should also be
      noted that the tests were carried out under laboratory conditions and therefore
      do not include practices carried out by scrubbed staff that could affect the
      results.

PMID- 11993299
TI  - Bradykinin and the cardiovascular system.

PMID- 11993300
TI  - Hemodynamic findings in 123 patients with acute myocardial infarction on
      admission.
AB  - Hemodynamic and clinical evaluations of 123 patients with acute myocardial
      infarction were performed during the first hour of admission to the hospital. In
      the 123 patients, the right atrial pressure was less than 10 mm Hg in 49
      patients, the right atrial oxygen saturation was less than 70% in 97 patients,
      the arteriovenous oxygen difference was greater than 5.0 vol% in 78 patients. The
      arterial Po2 was less than 90 mm Hg in 101 of 107 patients who could be evaluated
      while breathing room air. The cardiac index was depressed below 3.0 L/min/m2 in
      65 of 98 patients. The hemodynamic findings generally correlated with the
      clinical status of the patient; however, within each clinical class of patients
      there was a wide spectrum of values for each measurement evaluated. There was
      also considerable overlap of the values found within each clinical
      classification. It is concluded that hemodynamic evaluation of patients with
      acute myocardial infarction presents a profile of the patient which is frequently
      different from the profile that clinical evaluation presents. An objective
      hemodynamic classification of patients with acute myocardial infarction may
      provide a more useful index for the evaluation of the patient's prognosis and for
      the assessment of preventative therapy.

PMID- 11993301
TI  - Indirect assessment of left ventricular performance in acute myocardial
      infarction.
AB  - One hundred patients admitted to a cardiac care unit had indirect serial
      determinations of left ventricular systolic ejection times. Patients were divided
      into groups with transmural infarction, nontransmural infarction, and no
      infarction, according to clinical, biochemical, and electrocardiographic
      criteria. Total electromechanical systole and left ventricular ejection time were
      shortened in acute myocardial infarction, whereas the pre-ejection period and its
      components, the Q-S1 and isovolumic contraction time intervals, were prolonged.
      The most abnormal measurements were observed in patients with transmural
      infarction. Patients with nontransmural infarction demonstrated less severe
      abnormalities of the systolic ejection times, and the patients without infarction
      were the least affected. Some of the greatest deviations in the measured
      intervals were observed in the transmural infarction patients who died. Indirect
      measurement of left ventricular systolic ejection time is a valuable adjunct in
      the bedside assessment of left ventricular performance and provides a prognostic
      index for patients with acute myocardial infarction.

PMID- 11993302
TI  - Hemodynamic determinants of exercise ST-segment depression in coronary patients.
AB  - Eight patients with coronary heart disease were studied during two periods of
      exercise separated by 30 min of rest; workload was increased in a stepwise
      fashion every minute of exercise up to a level that produced limiting symptoms of
      angina, fatigue, or dyspnea. The magnitude of ST-segment depression and the
      central aortic pressure were measured during exercise and recovery periods, and
      myocardial oxygen requirements were estimated by the pressure-time index
      (systolic aortic pressure x heart rate x ejection time). Seven of the eight
      patients exhibited a close relationship (r ranged from 0.74 to 0.98) between
      magnitude of exercise ST-segment depression and indices expressing myocardial
      oxygen requirements; heart rate, blood pressure, and ejection time were also
      related to magnitude of exercise ST-segment depression. These relationships were
      reproducible during two consecutive exercises. Like onset of angina, magnitude of
      exercise ST-segment depression is usually related to hemodynamic factors
      influencing myocardial oxygen needs. Consequently, comparisons of exercise
      induced ST depression before and after therapy (drugs, physical training, and
      surgery) are valid only if ECG findings are compared at the same level of
      myocardial oxygen requirements. In contrast, absence of such a relationship
      during recovery suggests an important difference in mechanisms of the post
      exercise electrocardiogram.

PMID- 11993303
TI  - Coronary heart disease. Differential hemodynamic, metabolic, and
      electrocardiographic effects in subjects with and without angina pectoris during
      atrial pacing.
AB  - Right atrial pacing was performed in 41 subjects with coronary heart disease.
      Twenty developed angina pectoris during pacing, while 21 did not. The extent of
      coronary artery disease, as judged by selective cinearteriography, was similar in
      the two groups. Both had significant increases in heart rate and pressure-time
      per minute, but there was no significant difference in either of these parameters
      between groups. Among the hemodynamic parameters measured, the only statistically
      significant change was in the cardiac index which fell slightly but significantly
      in the angina group. There were no differences in myocardial oxygen extraction
      either within each group or between groups. In the angina group, however, 14 of
      20 subjects exhibited abnormal myocardial lactate metabolism during pacing. The
      mean change was highly significant (P < 0.01). In the nonangina group, eight of
      21 subjects had abnormal lactate metabolism during pacing and the mean change was
      significant (P < 0.05). There was no correlation between abnormal lactate
      metabolism and electrocardiographic evidence of myocardial ischemia in either
      group. Sublingual nitroglycerin, given to five subjects with angina while pacing
      was continued, resulted in prompt relief of symptoms, but abnormal lactate
      metabolism and ST-segment depression were unaffected after 10 min. By contrast,
      when anginal symptoms were relieved in five subjects by cessation of pacing,
      symptomatic improvement was accompanied by marked improvement in lactate
      metabolism after 10 min. Although angina pectoris appears to be related
      statistically to subnormal left ventricular function and abnormal lactate
      metabolism, there is significant individual variation.

PMID- 11993304
TI  - Effects of training on the distribution of cardiac output in patients with
      coronary artery disease.
AB  - In nine patients with coronary artery disease, cardiac output distribution was
      evaluated at rest and during exercise by measurement of cardiac output and
      regional blood flow parameters (hepatic and muscle blood flow). In seven patients
      repeated values were obtained after a physical training program of 4 to 10 weeks'
      duration. After training, cardiac output was reduced at moderate work loads
      (13.1%) causing a change of the relation between oxygen uptake and cardiac output
      from hyperkinetic to normal. During heavy exercise the cardiac output was
      increased (5.5%) after training. Similar changes were observed in muscle blood
      flow, which was reduced at submaximal loads (14.9%) and increased at maximal
      (8.6%). Hepatic blood flow showed in contrast a less pronounced reduction at both
      work loads after training (difference, 7.2%). These effects of training could be
      explained as peripheral regulatory alterations without implying primary
      improvement in myocardial performance. They are consistent with the view that
      local changes in the trained muscles are important for the reduction in
      myocardial pressure-work caused by physical conditioning.

PMID- 11993305
TI  - Prediction of coronary heart disease based on clinical suspicion, age, total
      cholesterol, and triglyceride.
AB  - Our results, based on the definition of coronary heart disease by
      cinearteriography, show that definite relationships exist among incidence of
      coronary heart disease (CHD), age, total cholesterol (TC), and total
      triglycerides, with less definite ones between free cholesterol, and
      phospholipids for a specific group of 450 male patients referred to the Cleveland
      Clinic because of suspected coronary heart disease. Equations and graphs of the
      association of incidence of CHD with these conditions are presented. The
      relationships were strong enough to be of aid in discriminating CHD from normal;
      the most useful being age, TC, and TG. Incidence determinations were presented in
      terms of total incidence and incidence associated with the variable itself.
      Coronary angiography demonstrated 350 CHD and 100 normals or a ratio of 3.5 to 1.
      This ratio is a reflection of the high accuracy with which physicians suspect
      CHD. Age and TC were good discriminators in these patients suspected of CHD. An
      improved relationship and better discrimination was obtained by relating
      incidence simultaneously to age, TC, and TG. The probability of having CHD is the
      total incidence corresponding to the patient's age, TC, and TG. The probability
      level of 0.90 gave 95% assurance of a correct prediction for the physician
      selected group of patients. Twenty-nine per cent of them had probabilities above
      0.90.

PMID- 11993306
TI  - Cinecoronary arteriography in young men.
AB  - Of a group of 723 men less than 40 years old who underwent cinecoronary
      arteriography primarily for evaluation of chest pain, 357 (49%) were found to
      have at least 50% narrowing of one or more coronary arteries. The youngest person
      was 17 years old. The distribution of lesions in the young men was similar to
      that found earlier in a study of persons not selected by age. The anterior
      descending coronary artery was most frequently affected; the right coronary
      artery was most often totally occluded. No total occlusions of the left main
      coronary artery were seen. Electrocardiographic evidence of myocardial
      infarction, found in 109 patients, was less common with disease of the circumflex
      or right coronary arteries than with disease of the anterior descending coronary
      artery. This observation was confirmed by examination of left ventriculograms for
      areas of decreased contractility. Six patients had no significant arterial
      narrowing. The extent of arterial involvement seemed to be related to the
      duration of symptoms in patients who had angina pectoris or myocardial
      infarctions. Clinical diagnoses correlated well with the angiographic findings,
      particularly in those men considered to be normal and those with typical angina
      pectoris. Addition of atypical features or prolonged pain decreased the degree of
      correlation. Only 20% of those with cholesterol levels less than 200 mg/100 ml
      had significant lesions, whereas 81% with levels more than 275 mg/100 ml had such
      findings.

PMID- 11993307
TI  - The P wave and P-R interval. Effects of the site of origin of atrial
      depolarization.
AB  - The atria of 37 patients were paced from selected sites during cardiac surgery.
      When the atria were paced from endocardial sites low in the right atrium, the P
      waves in ECG leads II, III, and aVF were shown to be either negative, biphasic,
      or positive, depending on the site paced. When the endocardial sites were paced,
      the P-R intervals were, almost without exception, less than 0.12 sec. When those
      endocardial sites closest to the A-V junction were paced, the P-R intervals were
      always less than 0.12 sec. When the atria were paced, from the epicardial sites,
      the P-R intervals were always greater than 0.12 sec. Negative P waves in ECG
      leads II, III, and aVF were recorded when the atria were paced from the postero
      inferior left atrium and the caudal right atrium. The P-R interval did not always
      reflect the initial period of atrial activation because an isoelectric interval,
      generally of 0.01 to 0.025 sec, was frequently present between the onset of
      atrial stimulation and the first clear evidence of the P wave in the ECG. The
      implications of these results are discussed.

PMID- 11993308
TI  - The mechanism of supraventricular tachycardia.
AB  - In six successive patients, none of whom had the Wolf-Parkinson-White syndrome,
      recurrent episodes of paroxysmal supraventricular tachycardia (SVT) were analyzed
      to determine the mechanism by which this arrhythmia is initiated and sustained.
      In each patient, simultaneous intracavitary atrial electrograms and surface
      electrocardiograms were recorded during the onset of numerous spontaneous
      episodes of SVT. Atrial premature depolarizations (APD) produced by programmed
      stimulation sequences were used to measure atrioventricular refractory periods
      and to produce atrial echoes and episodes of SVT. Stimulated APDs introduced
      during sustained episodes of SVT either altered its behavior or terminated it.
      The electrophysiologic behavior of SVT in these patients strongly suggests that
      the mechanism responsible for paroxysmal supraventricular tachycardia is atrial
      reentry utilizing the A-V conducting system.

PMID- 11993309
TI  - The mechanism of synchronization in isorhythmic A-V dissociation. II. Clinical
      studies.
AB  - The electrocardiographic patterns recorded from seven patients with isorhythmic A
      V dissociation fall into two distinct groups. In pattern I, the P wave fluctuates
      cyclically back and forth across the QRS complex. The mechanism responsible for
      this type of A-V synchronization represents a typical biologic feedback control
      system. The P-R interval is a determinant of stroke volume, which in turn
      influences the arterial blood pressure. The blood pressure has an inverse effect
      on the discharge frequency of the S-A node through the baroreceptor reflex. The S
      A nodal frequency then affects the P-R interval, to close the feedback loop. In
      pattern II, the P wave is in a fairly constant position relative to the QRS
      complex. It is usually coincident with the QRS complex or appears on the ST
      segment or first half of the T wave. The mechanism producing synchronization in
      pattern II type of isorhythmic dissociation has not been established
      conclusively.

PMID- 11993310
TI  - Transvenous cardiac pacing. Technics for optimal electrode positioning and
      prevention of coronary sinus placement.
AB  - Optimal electrode position for long-term transvenous cardiac pacing is in the
      apex of the right ventricle. Intracardiac electrograms, surface
      electrocardiograms, frontal fluoroscopy, lateral roentgenograms, and pacing
      threshold levels were studied in two groups of patients: One group was comprised
      of five patients with permanent pacemakers who had inadvertent malplacement of
      the pacing catheter, and the second group was composed of six patients undergoing
      temporary pacing from selected sites within the coronary venous system. The
      results of this study indicate that the appearance of a characteristic right
      ventricular endocardial complex recorded from the catheter tip is the most
      reliable guide to proper electrode placement. Low threshold levels, good position
      demonstrated roentgenographically, and typical surface electrocardiographic
      patterns of left bundle-branch block were all noted during intentional and
      following inadvertent malpositioning of the electrode within the coronary venous
      system and do not, therefore, guarantee proper positioning. A successful routine
      for pacemaker insertion has been established which includes fluoroscopy, lateral
      roentgenograms, intracardiac and surface electrocardiograms, and threshold
      analysis. Satisfaction of all these tests appears to insure proper electrode
      positioning.

PMID- 11993311
TI  - Hemodynamic changes following correction of severe aortic stenosis using the
      Cutter-Smeloff prosthesis.
AB  - Twelve patients with pure or dominant stenosis were studied before and after
      aortic valve replacement (Cutter-Smeloff). The changes in cardiac output and A-V
      O2 difference were small and insignificant, but exercise stroke volume increased
      from 72 to 96 ml after the surgery. The aortic peak systolic gradient was 92 +/-
      29 mm Hg before and 4 +/- 9.8 mm Hg after surgery. The PA wedge pressure, taken
      as a measure of the LV diastolic pressure, decreased from 18 mm Hg to 12 mm Hg at
      rest and 30 mm Hg to 16 mm Hg on exercise. The PA pressures also decreased from
      37/18 (mean, 26) to 28/11 (17) mm Hg at rest, and 61/31 (43) to 41/17 (27) mm Hg
      on exercise, but the PA and PA wedge pressures maintained their tendency to
      increase in a linear manner with oxygen consumption (Vo2) on exercise after
      surgery. As a result of decreased wedge pressure, the pulmonary vascular
      resistance also decreased significantly afterward. The adequacy of cardiac output
      at rest and on exercise expressed by cardiac output as the linear function of Vo2
      improved toward the normal (values before operation, CO = 2.78 + 0.0069 Vo2, r =
      0.84; after operation, CO = 3.80 + 0.0062 Vo2, r = 0.91). The exercise factor
      (delta CO/delta Vo2) or the regression coefficient, however, was similar before
      and after surgery. The hemodynamic result was satisfactory although some
      abnormalities of the left ventricular function persisted after operation.

PMID- 11993312
TI  - Therapeutic defibrination and heparin therapy in the prevention and resolution of
      experimental venous thrombosis.
AB  - The application of phenol to the femoral veins of anesthetized dogs resulted in
      an occluding thrombus in 24 of 25 veins at 1 week. Serial venography and eventual
      histology showed that these veins remained occluded over a 5-week observation
      period, the thrombi undergoing organization. Therapeutic defibrination was
      achieved with administration of an enzyme from venom of the pit viper (Arvin).
      Arvin, administered for 1 week immediately following phenol application and
      before thrombus formation had occurred, prevented thrombosis in all 10 such
      veins, and serial venography for a further 4 weeks showed that the veins remained
      patent. Administration of Arvin was begun 24 hours postoperatively, when
      venography had demonstrated an occluding thrombus and failed to clear any of 11
      veins after 3 weeks of treatment. Intravenous administration of heparin, 10,000
      units, at 6, 6, and 12-hour intervals in a 24-hour period, was begun immediately
      after phenol application and continued for 1 week; 10 of 12 veins were blocked at
      1 week. Following the same dose of heparin every 6 hours four of eight veins were
      blocked at 1 week. The results indicate that when the vascular endothelium is
      damaged, therapeutic defibrination is more effective than heparin therapy in
      preventing venous thrombosis. Arvin therapy has no significant thrombolytic
      effect even if the thrombus is less than 24 hours old.

PMID- 11993313
TI  - Atresia of the left atrioventricular orifice associated with a Holmes heart.
AB  - The first well-documented case of Holmes heart associated with an atretic left
      atrioventricular orifice is reported. The Holmes heart may be considered as a
      single ventricle in which the main chamber has the morphologic characteristics of
      a left ventricle, the infundibular chamber is not inverted, and the great
      arteries are normally arranged. The importance of this report is greater than its
      simple description since it definitely establishes the coexistence of a true
      single ventricle and atresia of the atrioventricular orifice is possible.

PMID- 11993314
TI  - Splitting of second heart sound in patients with aortic regurgitation.
AB  - The intervals between the two components of the second heart sound (A2-P2),
      measured from the phonocardiograms of 50 patients with severe aortic
      regurgitation, were compared with those of 57 normal subjects. During expiration
      the second sound was single or closely split in both groups. Inspiratory
      augmentation of the A2-P2 interval of less than 0.02 sec occurred in one normal
      subject (2%) and in 42 patients with aortic regurgitation (86%). Thus the great
      majority of patients with severe aortic regurgitation had either a single or a
      closely split second heart sound during both phases of respiration. The mean Q-A2
      intervals (rate corrected) of 30 patients, in whom severe aortic regurgitation
      was documented by contrast angiographic studies, were longer than those of normal
      subjects during both phases of respiration, and the difference was statistically
      more significant (P < 0.02) during inspiration. Thus prolongation of the Q-A2
      interval was the main factor responsible for the disappearance of the normal
      asynchrony of semilunar valve closure, in patients with aortic regurgitation.

PMID- 11993315
TI  - Medico-Chirurgical Transactions. A cardiovascular cluster.
AB  - A cluster of papers, important to the history of cardiology and cardiovascular
      surgery, that were published in volume 1 of Medico-Chirurgical Transactions
      (1809), are discussed. These include articles by Sir Astley Cooper on ligature of
      the common carotid artery for aneurysm, John Abernethy on mitral stenosis, and
      Sir David Dundas on acute rheumatic carditis.

PMID- 11993316
TI  - Spontaneous release of T cell receptors for alloantigens. III. The effects of
      anti-T cell receptor antiserum, of alloantiserum and of trypsin on T cell
      receptor release.
AB  - Spleen and lymph node T lymphocytes cultivated in vitro spontaneously released
      receptors for alloantigens. Among the various specificities, those receptors
      fitting certain alloantigens could be absorbed by formolized cells or proper
      genotype without influencing receptors for other alloantigens. Shedding of T cell
      receptors could be inhibited for 8 h by treating cells with antisera directed
      against T cell receptors (anti-RS antisera). Inhibition experiments indicated
      that resynthesis of T cell receptors appears to be complete by 8 h. Experiments
      on prevention of receptor shedding revealed highly specific and presumably
      cytotoxic elimination of T cells with receptors for given alloantigens. Treatment
      of cells with alloantiserum obtained by skin graft rejection failed to inhibit
      spontaneous release of T cell receptors, whereas treatment of lymphocytes with
      trypsin resulted in an 8-h delay of receptor shedding similar to that after
      treatment of cells with anti-RS antisera. This inhibition was, however,
      nonspecific.

PMID- 11993317
TI  - I-region-associated determinants: expression on mitogen-stimulated lymphocytes
      and detection by cytotoxic T cells.
AB  - We have studied the expression of Ia-antigens, controlled by genes in the I
      region of the H-2 complex, on phytohemagglutinin (PHA)-stimulated lymph node
      cells and on lipopolysaccharide (LPS)-stimulated spleen cells, and have compared
      these two types of cell populations as targets for killer cells in the cell
      mediated lympholysis (CML) assay. PHA targets are almost completely insensitive
      to complement-mediated lysis by anti-Ia sera while the majority of LPS targets
      are killed. T cell-mediated lysis against I-region determinants was also
      detected, and these determinants, in contrast to H-2K and H-2D CML determinants,
      seem to be much more strongly expressed on LPS-stimulated cells. No differences
      in the kinetics of the response to K- or I-region CML determinants were observed.
      Lysis by killer cells can also be obtained against incompatibilities which do not
      give rise to strong skin graft rejection and against determinants which are most
      probably controlled by genes outside the K-D interval.

PMID- 11993318
TI  - Derangements of immunoglobulin levels, phytohemagglutinin responsiveness and T
      and B cell markers in Down's syndrome at different ages.
AB  - Immunologic studies were performed in 83 patients with Down's Syndrome (DS) in
      ages ranging from a few months to 30 years and 76 karyotypically normal age
      matched controls. The results show that both thymus-dependent and independent
      functions were impaired in DS with a characteristic age sequence. Serum
      immunoglobulin levels were normal in children with DS less then 5 years old;
      after 6 years of age a definite hyperglobulinemia of the IgG and IgA type was
      observed. A slight decrease in IgM was observed between 16 and 25 years of age.
      In subjects with DS lymphocyte phytohemagglutinin responsiveness was in the
      normal range during the first decade but it decreased thereafter progressively;
      the percentage and absolute number of peripheral blood lymphocytes forming
      "spontaneous rosettes" with sheep erythrocytes were abnormally low at all ages
      including infancy; the number of circulating lymphocytes with a high density of
      surface immunoglobulins was always in the normal range.

PMID- 11993319
TI  - In vitro studies on the selective binding of IgG from different species to tissue
      sections of the bovine mammary gland.
AB  - Tissue sections of the mammary gland of cattle provide a sensitive and
      reproducible model for studying the initial events of the selective transport of
      bovine IgGs by the acinar epithelium (AE). Mammary tissue was reacted with
      purified antibody to horseradish peroxidase (HRP) and exposed to HRP. The sites
      of peroxidase activity were revealed cytochemically. The highly selective binding
      of IgGs by AE of the colostrum-forming gland but never of the lactating gland was
      most notable, whereas IgG1 and IgG2 subclasses and IgM and IgA lacked any binding
      capacity. An inhibition assay showed that the inhibitory capacity of IgGs was
      abolished by either alanylation or acetylation, whereas binding of IgGs was
      blocked by both Fab/c and isolated H-chains, but not by F(ab')2, Fab and Fc. The
      inhibitory pattern suggests that the region on the IgGs molecule involved in
      binding to the AE receptor may be located within the CH2 domain. In addition, IgG
      preparations of human, sheep and rabbit origin were found to be equally efficient
      in inhibiting the binding of IgGs to AE, whereas no inhibition was obtained with
      nonmammalian (turtle and chicken) IgG. Similarly, human myeloma proteins of the
      subclasses IgG1 and IgG3 caused complete inhibition, while IgG2 and IgG4 were
      inefficient. It is suggested that molecular evolution of IgG within mammalian
      species is accompanied by the conservation of structures fitting to receptors on
      the cell surface of different species.

PMID- 11993320
TI  - Specific unresponsiveness in nude mice given antigen before T cells.
AB  - Nude mice given antigen before being given congenic T cells are specifically
      tolerant to that antigen and recovery of the ability to respond takes at least 2
      weeks. If, after giving antigen, spleen cells are transferred to irradiated
      congenic recipients together with normal congenic thymocytes, the recipients
      usually remain unresponsive. Treatment of the spleen cells with supernatant from
      lysed cells renders them responsive in transfer. Spleen cells from unresponsive
      mice do not suppress normal spleen cells in transfer and the unresponsiveness is
      not broken by allogeneic cells. It is therefore probable that this is a case of
      reversible blocking of the B cell receptors and that T cells are not involved.

PMID- 11993321
TI  - Formation of plaques by adherent spleen cells from nonimmunized mice, incubated
      in vitro with the nonadherent fraction of immune allogeneic cells.
AB  - Twenty-four-hour incubation of adherent spleen cells from normal C57BL mice with
      purified nonadherent spleen cells from CBA mice, in the peak of their primary
      response against sheep red blood cells, resulted in the appearance of plaque
      forming cells in the adherent cell population. The immunological nature of these
      plaques was demonstrated by their complement dependency and the inhibitory effect
      of specific anti-mouse IgM serum. Direct, but not indirect plaque formation was
      found to be associated with the adherent cell population for which direct cell to
      cell contact is necessary. Experiments with cytotoxic specific anti-strain sera
      revealed that in this system, the adherent plaque-forming cells are the nonimmune
      adherent C57BL cells.

PMID- 11993322
TI  - Inhibition of mixed leukocyte culture by anti-idiotypic antibodies.
AB  - (CBA x C57BL/6)F1 antisera prepared by injecting F1 mice with CBA T lymphocytes
      or CBA anti-C57BL/6 alloantibodies were tested for their ability to inhibit the
      mixed leukocyte culture (MLC) response. Presence of antiserum throughout the
      culture period in the absence of complement did not have any effect on the MLC
      response. Treatment of CBA responder cells with F1 antiserum and complement prior
      to the culture specifically inhibited the MLC response. Specificity of the
      suppression was ascertained; absorption of the F1 sera with F1 or C57BL/6 spleen
      cells did not remove the suppressive factor, whereas absorption with CBA spleen
      cells did so. F1 antiserum treatment left intact the response to third party
      alloantigens (DBA/2). Immunabsorbent columns with alloantibody of corresponding
      specificity removed the suppressive factor from anti-T cell sera as well as from
      antisera to alloantibody. The data suggest that the circulating alloantibody
      population contains molecules which share idiotypic determinants with surface
      receptors on T cells recognizing the same alloantigens.

PMID- 11993323
TI  - Separation of antigen-specific lymphocytes. A new general method of releasing
      cells bound to nylon mesh.
AB  - Inserting a disulfide bridge between nylon and hapten or antigen allows the
      release of fiber bound cells by cleaving the disulfide bond with 10(-4) M 2
      mercaptoethanol at 4 degrees C. Four to 12-fold enrichments in specific precursor
      cells could be obtained. The method is compared with the thermal release
      previously used. The T and B cell content of the specific fraction was
      determined. It is suggested that the low enrichment in plaque-forming cells of
      the hapten-specific fraction found after stimulation with antigen in vitro might
      be due to the fact that there is also enrichment for suppressor cells in the
      specific fraction.

PMID- 11993324
TI  - Permissiveness of athymic ("nude") mice towards congenic memory cells.
AB  - Spleen cells from BALB/c or BALB-Igb mice immunized against the determinant oligo
      D-alanine were transferred to the following recipients: normal BALB/c; lethally
      irradiated BALB/c; and congenitally athymic BALB/c-nu. Irradiated as well as nude
      recipients permitted the development of a strong adoptive antibody response,
      while the response in normal BALB/c recipients was very low ("isogeneic
      barrier"). Using allotypically marked spleen cells from BALB-Igb donors it was
      shown that the antibodies in irradiated as well as in nude recipients were
      produced by donor cells. The same conclusion was drawn by assessing isoelectric
      focusing spectra, which in each transfer displayed the individually
      characteristic pattern of the donor. In addition to specific antibodies, the
      donor cells produced considerable levels of IgG, as characterized by allotype,
      but again only in nude and in irradiated recipients. The ready permissiveness of
      nude recipients towards congenic memory cells could be abolished when prospective
      recipients were restored, some time prior to transfer, by BALB/c thymus or BALB/c
      spleen cells. The results are interpreted to suggest that the isogeneic barrier
      in normal recipients is due to a thymus-dependent suppression or rejection of
      memory cells by the recipients.

PMID- 11993325
TI  - Effect of alloantisera on the immune response of rat spleen cells against sheep
      red blood cells in vitro.
AB  - Alloantisera directed against antigens determined by the major histocompatibility
      system or by the genetic background of the rat are able to completely inhibit the
      primary IgM immune response of rat spleen cells against sheep red blood cells in
      vitro. Full inhibition is elicited only when the alloantisera are added during
      the first 48 hours of cultivation. Alloantisera that inhibit a primary immune
      response do not inhibit a secondary IgM response to sheep red blood cells in
      vitro by spleen cells primed 10-28 days before.

PMID- 11993326
TI  - A theory of regulation and self-nonself discrimination in an immune network.
AB  - A mechanism is suggested for the regulation of the immune response that involves
      antigen-binding and anti-idiotypic lymphocytes. The cross-linking of receptors is
      postulated to be a general mechanism for triggering T cells, B cells and
      cytotoxic effector cells (e.g. macrophages). A key role in regulation is ascribed
      to antigen-specific T cell-dependent factors, which are assumed to be able to
      block the receptors of both T cells and B cells of the anti-idiotypic
      specificities. The simple postulates of the model lead to feasible mechanisms for
      the helper, suppressor and killer roles of T cells, cellular and humoral immune
      responses, low zone tolerance and the tolerogenic effects of monomers, immune
      memory, antigenic competition, the abrogation of tolerance with cross-reacting
      antigens, the usefulness of the switch from IgM to IgG, and self-tolerance to
      both serum antigens and cell surface antigens. Biological roles are suggested for
      one of the Ia antigens and beta 2-microglobulin. The theory leads to a number of
      predictions, which can be tested experimentally. A simple mathematical model is
      included, which provides an indication of how the theory may be further developed
      on a quantitative basis.

PMID- 11993327
TI  - Differences in the immunological activities of antibody-secreting cell precursors
      in mouse spleen selected on the basis of antigen-binding capacity.
AB  - Mouse spleen cells transfer a retarded and lower than normal IgG antibody
      response after removal of cells with a high antigen-binding capacity. The
      population enriched in these latter cells transfers a response equal to or, more
      often, higher than the response of the unfractionated controls and does not
      appear to have originated from previous priming of the mice. These cells are
      present in athymic nude mice and appear to be more susceptible to inactivation by
      an anti-Ig antiserum and complement than precursors of IgM antibody-secreting
      cells.

PMID- 11993328
TI  - The development of the thymus in the nude mouse.
AB  - The developing thymus of nude mouse embryos (derived from homozygous, nu/nu x
      nu/nu, matings) has been examined from 13 days' gestation onwards for the
      presence of large basophilic stem cells or their lymphoid progeny. No trace of
      either stem cells or lymphocytes has been found at any stage, indicating that
      from the earliest stages of thymic development lymphopoiesis is defective.
      However, histological evidence alone is not sufficient to rule out the
      possibility that small numbers of lymphocytes may be present in the nude thymus.
      Recent evidence that nude mice born of heterozygous (nu/+) females possess some T
      lymphocytes and "T lineage" cells is discussed in relation to these findings. A
      series of morphological changes have been defined within the epithelial component
      of the developing nude thymus, further analysis of which may help to determine
      the nature of the thymic defect.

PMID- 11993329
TI  - Bursa lymphocytes and IgM-containing cells in chicken embryos bursectomized at 52
      64 hours of incubation.
AB  - A technique of surgical removal of the bursal primordium ("bursectomy") of
      chicken embryos at stage 17, approximately 52-64 hours and 29-32 somites, is
      described. The survival rate of bursectomized (Bx) embryos approached a level of
      50% on the 21st day. About 20% of correctly Bx embryos exhibited malformations of
      the anal sphincter and the large intestine. Using a rabbit anti-bursacyte serum,
      which did not react with thymocytes, the specific bursa-derived cell (Bu) marker
      was detected on the surface of bursa, spleen, bone marrow and thymus lymphocytes.
      Early embryonic bursectomy caused a moderate depletion of Bu marker-bearing and
      IgM-containing cells. It has been postulated that embryonic Bu cells can be
      recruited from sites other than the bursa and in the absence of the bursa.

PMID- 11993330
TI  - Induction of T and B cell immunity by anti-idiotypic antibody.
AB  - A small dose of the IgG1 fraction of anti-idiotypic antibody (aId1) raised in
      guinea pigs against a strain A/J antibody specific for streptococcal Group A
      carbohydrate sensitizes A/J mice against Group A streptococci. This is opposed to
      the previously established suppressive function of anti-idiotypic antibody of the
      IgG2 class (aId2). Correspondingly, aId1 but not aId2 is eliminated from the
      circulation in the way typical of an immunogenic molecule. However, the
      stimulatory component in the IgG1 fraction is not necessarily itself IgG1
      antibody. Sensitization occurs in both B and helper T lymphocytes and is specific
      for Group A streptococci. In the B cell compartment sensitization is restricted
      to precursor cells expressing the idiotype. The concomitant activation of T
      helper cells therefore suggests that these cells make use of receptors with a
      similar or identical idiotype. Efficient sensitization by aId1 of both T and B
      cells is also demonstrated in strain C57L/J mice which upon immunization with
      Group A streptococci express a partially cross-reacting idiotype as a minor
      component. When such animals were primed with aId1, essentially all of the anti
      carbohydrate antibody carried the partially cross-reacting idiotype.

PMID- 11993331
TI  - Kinetics of the reactive cell clones after immunosuppression and induction of
      tolerance. II. Different recovery of 19 S and 7 S plaque-forming cells after
      induction of tolerance.
AB  - By the aid of two alkylating agents (cyclophosphamide (CP) and 036.5122, (Asta),
      applied after a single dose of antigen, tolerance to sheep red blood cells
      (SRBC), has been induced in NMRI mice. Duration and characteristics of recovery
      were followed by a second antigenic challenge at various time intervals and by
      determination of 19 S and 7 S plaque-forming cells (PFC) 4 days later. During
      recovery from the tolerant state two phases of responsiveness could be
      differentiated: an early phase with no or markedly reduced numbers of total PFC,
      all of them being of the IgM type; a later phase with a steady increase in total
      PFC up to normal values, paralleled by an increase in the proportion of 7 S PFC
      finally reaching 90% of total PFC. In comparison with CP, recovery from tolerance
      induced by equitoxic doses of 5122 were delayed and modified. Even after 8 weeks,
      total PFC to SRBC were still depressed, and the ratio 19 S/7 S PFC resembled
      neither a typical primary nor secondary pattern. It is concluded that CP-mediated
      immunological tolerance is followed spontaneously by the establishment of a
      memory state. This observation, in agreement with findings of other authors, is
      interpreted as the expression of an established B cell memory compartment during
      the period of deficient T cell activity. The long-lasting modification of
      specific responsiveness after 5122 indicates a profound disturbance of the
      potency to recover from the impact of this alkylating agent, the biological base
      of which is as yet unidentified. It is suggested that observation of the
      characteristic features during the recovery phase from tolerance may help to
      clarify the nature of the defect in specific responsiveness.

PMID- 11993332
TI  - Energy requirements of the binding and lytic steps of T lymphocyte-mediated
      cytolysis of leukemic cells in vitro.
AB  - The process of T lymphocyte-mediated destruction of target cells in vitro is
      temperature dependent and is suppressed by inhibitors of energy metabolism, but
      the energy requirements for the conjugation and lytic steps of the process are
      different. The conjugation step of lymphocytes and target cells is prevented by
      metabolic inhibitors and is dependent on temperature, increasing in the range
      from 2 degrees C to 22 degrees C. However, after lymphocyte-target cell
      conjugates are formed, they are stable at low temperatures (0 degree C) and in
      the presence of metabolic inhibitors. Thus, the formation but not the maintenance
      of lymphocyte-target cell conjugates is an energy-dependent process. In contrast
      to the conjugation step, which is influenced both by metabolic inhibitors and by
      temperature, the lytic step, which occurs only between 22 degrees C and 37
      degrees C, is not affected by inhibitors of energy metabolism. The sigmoidal
      behavior of lysis as a function of temperature, showing a sharp inflection around
      20 degrees C, can be explained in terms of the alteration of the viscosity of the
      membrane matrix of the target cells rather than as a general metabolic effect on
      the killer and target cells.

PMID- 11993333
TI  - Specific B lymphocyte suppression by infectious bursal agent (Gumboro disease
      virus) in chickens.
AB  - Chickens infected experimentally with infectious bursal agent (IBA) during
      embryonation or early after hatching show a severe depression of bursa-dependent
      lymphoid components, and associated immune functions. Data presented here and
      elsewhere show that the degree of B cell suppression correlates with the time of
      infection. This would be compatible with a virus-induced block in B lymphocyte
      differentiation. Accordingly, the virus may be cytopathic for early (bursal) but
      not late (circulating) B lymphocytes or, more likely, the virus inactivates those
      non-lymphoid bursal cells mediating lymphocyte differentiation.

PMID- 11993334
TI  - Studies on sperm antigenicity. IV. Lymphocyte cytotoxicity in cell-mediated
      response to homologous spermatozoa.
AB  - In the presence of specific antigen, lymph node cells from Rockefeller strain
      guinea pigs with delayed hypersensitivity to homologous spermatozoal antigen
      produced progressive destruction of L929 cell monolayers. This effect was
      measured by counting surviving target cells removed from Leighton tubes by
      trypsin treatment as well as by standard cell counts in microplates. The
      cytotoxic effect was immunologically specific since neither sperm-sensitized
      lymphocytes in presence of unspecific antigen nor normal lymph node cells with
      guinea pig sperm, induced target cell destruction. The effect required an antigen
      concentration equal to, or greater than, 70 micrograms protein/ml. A ratio of
      100:1 of sensitized lymphoid cells to target cell was found to be optimal. L-cell
      lysis could be demonstrated at day 14 and reached its peak on day 21 after
      immunization. A high level of correlation between lymphocyte cytotoxicity and
      macrophage migration inhibition was found. The role of lymphocyte cytotoxicity in
      cell-mediated immunity to spermatozoa is discussed as one of the possible
      mechanisms leading to destructive changes in the testes.

PMID- 11993335
TI  - The clonal origin of cells contributing to successive phases of a cyclical immune
      response.
AB  - A single injection of mice with a low dose of sheep red blood cells results in a
      cyclic appearance of antibody-forming cells of the IgG classes. The peaks of the
      responses occur at the same time in the spleen and the thoracic lymph nodes. We
      have investigated the phenomenon with respect to IgG2a response by using the
      isoelectric focusing overlay assay and have assumed that in the great majority of
      cases, after immunization with limiting amounts of antigen, an individual
      spectrotype represents a "clonal" product. Enumeration of spectrotypes which
      arise only in the first peak and those which arise only in the second, suggests
      that the second peak of plaque-forming cells can be accounted for on the basis of
      the stimulation of a second population of precursor cells. Several possible
      mechanisms whereby new antigen-sensitive precursor cells can be turned on late in
      a primary response are discussed.

PMID- 11993336
TI  - Cross-reactivity patterns of IgM and IgG anti-lipopolysaccharide antibodies in
      individual mice.
AB  - A sensitive method has been developed which permits comparative analysis of IgM
      and IgG antibody specificity against lipopolysaccharide (LPS) antigen. It is
      based on hemolysis of LPS-coated red blood cells and on its inhibition by
      homologous and heterologous LPS. By appropriate use of anti-immunoglobulin sera,
      indirect (facilitated) lysis due to IgG antibodies is obtained, whereas IgM gives
      direct lysis and is 2-mercaptoethanol-sensitive. IgG can be analyzed either by
      facilitation with a rabbit anti-mouse Ig or with anti-allotype sera. By use of
      anti-allotype sera in F1 hybrids, both parental antibody types can be studied
      separately. Antibodies of either class from individual mice may display different
      cross-reactivity patterns. Furthermore, for IgM and IgG within a given serum,
      both similarities and differences have been found. Some of the cross-reactivity
      patterns have been followed over one year. With few exceptions, individual
      patterns remained constant throughout this period.

PMID- 11993337
TI  - Immunoglobulin-bearing lymphocytes of the chicken. I. Heavy chain immunoglobulin
      commitment and organ distribution.
AB  - When purified anti-immunoglobulin light chain antibodies were used in indirect
      immunofluorescence or labeled with 125I for autoradiographic staining, a similar
      percentage of Ig-bearing lymphocytes were detected by both techniques in lymphoid
      cell suspensions from the thymus or blood of 8-14-week-old chickens. However, a
      larger proportion of Ig positive lymphocytes were detected in suspensions of
      bursal cells by the more sensitive autoradiographic method, suggesting a lower
      surface density of Ig: perhaps on newly differentiated stem cells. In thymus and
      spleen suspensions, the proportions of Ig positive lymphocytes carrying mu and
      gamma-chains were roughly equal, whereas in the B cell populations of the bursa
      and blood, cells carrying surface gamma-chains predominated. IgA-bearing
      lymphocytes were only a minor population (< 5%) in lymphocyte suspensions
      prepared from the thymus, bursa, blood and spleen of adult chickens, but formed
      almost 50% of the Ig-bearing lymphocytes in the caecal tonsils.

PMID- 11993338
TI  - B cell tolerance induced by polymeric antigens. III. Dissociation of antibody
      formation and memory generation in tolerant mice.
AB  - Hapten (2,4-dinitrophenyl (DNP))-substituted type 3 pneumococcal polysaccharide
      (DNP-lys-S3) effectively suppresses both primary and secondary anti-DNP antibody
      responses to DNP-proteins. The present experiments show that tolerizing doses of
      DNP-lys-S3 have much less effect on B cell memory (re)generation in three
      distinct situations: (i) in serial transfers of DNP-protein-primed cells, (ii) in
      virgin mice tolerized before priming with DNP-hemocyanin, and (iii) in tolerized,
      hemocyanin-primed mice boosted with DNP-hemocyanin. Under some conditions
      tolerized mice developed 10-50% of normal memory in the absence of significant
      antibody formation. Isoelectric focusing analyses revealed that many B cell
      clones proliferate in tolerant mice, but produce very little antibody until
      transferred to further hosts. Clones that escape suppression in partially
      tolerant mice do not appear to be resistant to DNP-lys-S3, when retested. Since
      there is independent evidence that the generation of B memory cells is less T
      cell-dependent than the development of antibody-forming cells, these data are
      best explained by assuming that DNP-lys-S3 blocks lymphocyte cooperation. This
      would be expected to preferentially suppress antibody formation, and to spare
      memory generation.

PMID- 11993339
TI  - Suppression of immune responses to sheep red cell antigens in rats preimmunized
      with heterophilic antigen: cellular events.
AB  - Depression of humoral immune response to sheep red cells (SRC) has been observed
      in rats previously immunized with heterophilic (Forssman) antigen. Analogous
      phenomena were observed by assay of splenic plaque-forming cells obtained from
      rats immunized in vivo with heterophilic antigen (HA) and challenged with SRC.
      Isophilic immune responses were almost completely suppressed. Kinetics of the
      primary and secondary immune responses were analyzed. Intervals of two to four
      days between administration of HA and SRC yielded maximal suppression. Primary
      immune responses to SRC were determined in cultures of splenic cell suspensions
      derived from rats which had been either injected in vivo with HA or received no
      treatment. Under these conditions, too, administration of HA interfered with the
      antibody responses to SRC. Both adherent and nonadherent cells caused inhibition,
      with this property appearing earlier in adherent than in nonadherent cells. A
      hypothesis, capable of explaining the observations made in this study and
      compatible with similar phenomena described in other systems, has been proposed
      according to which after immunization with HA, SRC are diverted to HA-stimulated
      cells which are not equipped to deal with the antigen complex represented by SRC.

PMID- 11993340
TI  - Histocompatibility antigens and genetic control of the immune response in guinea
      pigs. II. Specific inhibition of antigen-induced lymphocyte proliferation by anti
      receptor alloantisera.
AB  - The in vitro recognition of acetylsalicilyl ovalbumin, penicilloylated bovine IgG
      (BPO-BGG) and the multichain copolymer poly-L-(Tyr, Glu)-poly-D L-Alapoly-L-Lys
      [(T, G)-A-L] by primed (2 x 13) F1 cells could be markedly and specifically
      blocked by alloantisera directed against "receptors" (R) or recognition
      structures for these antigens. The antisera were raised against lymphoid cells
      from various F2 hybrid guinea pigs of (2 x 13) histocompatibility type in which
      responsiveness to low doses of acetylsalicylic acid anhydride, BPO-BGG and (T, G)
      A-L segregated independently of each other. One of the genes required for the
      expression of high responsiveness appears to be linked to the 13 MHC genes. The
      anti-R antisera did not contain antibodies capable of interacting directly with
      the stimulating antigen since passage of the sera through antigen-immunoadsorbent
      columns did not remove antibodies capable of suppressing in vitro recognition.
      Furthermore, the antisera did not appear to contain cytotoxic antibodies directed
      against specific antigen-sensitive cells. The activity of the anti-R sera was
      highly specific: their inhibitory activity could only be absorbed by lymphoid
      cells bearing the specific recognition structures for the appropriate antigen.
      Preliminary experiments yield no indication that the anti-R antisera are specific
      for immunoglobulin idiotypes.

PMID- 11993341
TI  - The analysis of the monoclonal immune response to influenza virus. I. Production
      of monoclonal anti-viral antibodies in vitro.
AB  - Limiting numbers of spleen cells from mice primed with influenza virus were
      transferred into lethally irradiated syngeneic recipients. Upon antigenic
      stimulation of fragment cultures of the recipient spleens it was observed that a
      linear relationship existed between the number of transferred spleen cells and
      the number of responding fragments. The antibody product of individual fragments
      exhibited a highly restricted heterogeneity in isoelectric focusing as well as in
      its reactivity against various viral antigenic determinants. It was concluded
      that the limiting cell type in this adoptive transfer system corresponds to the
      virus-primed B cell which, upon antigenic stimulation, gives rise to a clone of
      antibody-producing cells. PR8-specific precursor B cells occurred at a frequency
      of at least 1/4000 splenic B cells in PR8-primed BALB/c mice. Approximately 25%
      of the stimulated cell clones produced sufficient quantities of antibody (200 ng)
      to render feasible an analysis of closely related viral antigens.

PMID- 11993342
TI  - Surface immunoglobulins on the lymphocytes of the skate Raja naevus.
AB  - Living lymphocytes of the Elasmobranch fish, Raja naevus, have been examined for
      surface immunoglobulin (Ig) by treatment with a fluorescent anti-Ig system. Large
      numbers of Ig-positive cells (60-80%) were found in peripheral blood, spleen and
      thymus. Following modulation of the surface Ig with anti-Ig, resynthesis
      occurred, showing that the surface Ig is a product of the individual lymphocytes
      rather than material passively absorbed from the serum. Formation of caps was
      independent of temperature, occurring as readily at 4 degrees C as at 20 degrees
      C, a finding which presumably reflects the environmental conditions normally
      experienced by the skate. The presence of Ig-bearing lymphocytes in the adult
      skate thymus suggests a similarity to the amphibian larval thymus, which may be a
      primary lymphoid organ for the production of both T and B lymphocyte analogues.

PMID- 11993343
TI  - A leukocyte migration inhibition assay technique using blood clot fragments in
      vitro.
AB  - Concomitantly with the capillary tube method, an in vitro leukocyte migration
      inhibition assay technique using blood clot fragments was performed in chicken
      egg albumin, Bacillus Calmette Guerin and complete Freund's adjuvant-treated
      immune guinea pigs. Results of both methods were concordant.

PMID- 11993344
TI  - Ringing endorsement.

PMID- 11993345
TI  - Nursing a cosy stereotype.

PMID- 11993346
TI  - Scotland goes back to first principles.

PMID- 11993347
TI  - Is stress an inevitable part of nursing?

PMID- 11993348
TI  - Being together in the moment.

PMID- 11993349
TI  - Leading lights.

PMID- 11993350
TI  - Silence is golden.

PMID- 11993351
TI  - Diary of a nurse with cancer. Boob talk.

PMID- 11993352
TI  - Crisis management.

PMID- 11993354
TI  - Living with disfigurement.
AB  - Body-image disturbance, as a consequence of disfigurement, affects a large number
      of people in the UK, yet there is little research into the psychosocial
      consequences. There is evidence that many of the psychological difficulties can
      be likened to phobic behaviour, particularly in social situations. A fear
      avoidance model of psychosocial difficulties following disfigurement is,
      therefore, potentially useful to nurses working in a variety of settings. The
      first of two articles on disfigurement explores some of the background to the
      fear-avoidance model.

PMID- 11993355
TI  - Preoperative fasting: we need a new consensus.
AB  - Fasting before surgery is necessary to avoid the risk of regurgitation and
      vomiting; it is also a legal requirement. But the current practice of fasting
      overnight or up to eight hours before surgery can cause dehydration, electrolyte
      imbalance, malnutrition and general malaise. Evidence shows that patients can
      benefit from receiving clear liquids up to three hours before surgery. Health
      care professionals need to be brought up to date with the latest evidence-based
      practice; national introduction of clear guidelines would help in this respect.

PMID- 11993356
TI  - Nursing with dignity. Part 7: Hinduism.
AB  - This article outlines the main beliefs and customs of Hinduism. It offers some
      guidelines to enable nurses to provide sensitive and appropriate nursing care to
      Hindu patients.

PMID- 11993358
TI  - The case for specialist mental health training.
AB  - Proposals that would fundamentally change the nature of nursing training are
      being examined by the new Nursing and Midwifery Council (NMC) without many nurse
      educators or practitioners having had an opportunity to catch up with the issues.
      This article puts the case for a broadening of the debate, particularly in
      relation to retaining a specialist training for mental health nurses.

PMID- 11993359
TI  - Professional development. Medicines. 1. Pharmacology.

PMID- 11993360
TI  - Life in the fast lane.

PMID- 11993363
TI  - Ripe for abuse. Farmworkers say organic growers don't always treat them as well
      as they do your food.

PMID- 11993364
TI  - Is there any end in sight? More priest sex-abuse cases, and new prosecutor
      scrutiny.

PMID- 11993365
TI  - That old-time, medicine. Innovative doctors are rethinking the office visit to
      put the care back in healthcare.

PMID- 11993366
TI  - A critical tipping point.

PMID- 11993367
TI  - [A case of demodicosis on a Dutch dairy farm].
AB  - Demodex bovis is a burrowing mite that lives in the hair follicles of cattle,
      resulting in nodules, granulomatous inflammation, and the formation of scar
      tissue. Clinical and histopathological changes of a recently diagnosed case of
      demodicosis on a Dutch dairy farm are presented before and after treatment.
      Treatment results were disappointing. The role of demodicosis in Dutch dairy
      farming is discussed.

PMID- 11993368
TI  - [DNA-diagnosis of congenital diseases in companion animals and the role of the
      practicing veterinarian].
AB  - The knowledge on the impact of gene defects on the development of disease in
      companion animals is increasing rapidly. The gene defects may be differentiated
      in an initiating defect, which is the cause of illness, and a promoting defect,
      which enhances the chance on illness. Up till now only initiating defects are
      known in dogs and cats. All this is of great importance for breeding purposes,
      because within a breed there is narrow relationship which means the genetic
      diversity is small, and with all the disadvantages thereof. The identification in
      good time of gene defects in breeding animals, so that these animals being
      excluded from breeding, is of utmost importance in preventing congenital
      diseases. For that reason more and more the owners will appeal to veterinary
      surgeons to cooperate in procedures to screen potential breeding animals, or to
      declare the animals free from gene defects. The problems with regard to the
      diagnostic tests, including the DNA-tests, and their predictive values are
      discussed.

PMID- 11993369
TI  - [Pre-operative disinfection in the cattle practice].

PMID- 11993370
TI  - [The role of antibiotics in lesions of the digestive tract in dogs and cats].

PMID- 11993371
TI  - [Hamburger disease not caused by hamburgers alone].

PMID- 11993372
TI  - [SRGN discontinued: what now?].

PMID- 11993373
TI  - [Annual report 'Commission Recommending Veterinary Products 2001'].

PMID- 11993375
TI  - [Not completely disagreable].

PMID- 11993374
TI  - [Just graduated].

PMID- 11993377
TI  - [New rules concerning long term sick leave by the law improving the gatekeeper].

PMID- 11993378
TI  - [Veterinary assistants].

PMID- 11993379
TI  - Platelet-rich plasma for dental implants and soft-tissue grafting. Interview by
      Arun K. Garg.

PMID- 11993380
TI  - Lateral proximal tibia bone harvest for use in augmentation procedures.
      Interview.

PMID- 11993381
TI  - A new polytetrafluoroethylene membrane for dental implant surgery. Interview by
      Arun K. Garg.

PMID- 11993382
TI  - [Suicide crisis in the elderly].

PMID- 11993383
TI  - [Vulnerability risk factors in the elderly].

PMID- 11993384
TI  - [The suicide crisis].

PMID- 11993385
TI  - [Preventive and therapeutic strategies in suicidal behavior].

PMID- 11993386
TI  - [Suicide crisis in the elderly. Security madness and risk evaluation in
      institutions].

PMID- 11993387
TI  - [The pre-admission visit, or when the nursing team moves].

PMID- 11993388
TI  - [Health promotion, from planning to development].

PMID- 11993389
TI  - [The rehabilitation of eggs and organ meats].

PMID- 11993390
TI  - [A sensory expression workshop for elderly patients with dementia].

PMID- 11993392
TI  - [New tariffs, reform or revolution?].

PMID- 11993393
TI  - [Intimacy, incontinence and nursing care of the elderly].

PMID- 11993394
TI  - [The elderly in institutions in 1988, social categories and revenues].

PMID- 11993396
TI  - [Old age, a new look].

PMID- 11993397
TI  - [The challenges posed by institutions for the elderly].

PMID- 11993398
TI  - [Searching for lost relationships].

PMID- 11993399
TI  - [Aging and dependence, when legal protection becomes necessary].

PMID- 11993400
TI  - [A look at social ties in old age].

PMID- 11993401
TI  - [Foreign body aspiration and the inhalation syndrome in the elderly patient].

PMID- 11993402
TI  - [A new approach to prevent violence among residents].

PMID- 11993403
TI  - ["Balance, or where are you?"].

PMID- 11993404
TI  - [Encouraging home care of dependent patients by experimenting with a
      communication tool].

PMID- 11993405
TI  - [Nutritional support procedures in elderly malnourished patients].

PMID- 11993406
TI  - [Reform of health establishments' pricing, last straight line before 2002].

PMID- 11993408
TI  - [Estimation of blood pressure, selected biochemical parameters and indices of
      left ventricular heart function in patients with mild or moderate essential
      hypertension treated with potassium losartan].
AB  - This study was conducted in 19 patients with mild or moderate essential
      hypertension randomised open trial to evaluate the influence of potassium
      losartan dosed 50 mg per day on blood pressure, metabolic processes and left
      ventricular heart function. The following intervals of examination were accepted
      at entry (before therapy with losartan) and then after 10 days; after 30 days and
      after 60 days of treatment. Mean values of arterial blood pressure and heart rate
      measured by conventional technics and obtained from 24-hour ambulatory monitoring
      data, biochemical results (serum levels of glucose, uric acid, creatinine,
      sodium, potassium, total cholesterol, HDL-cholesterol, LDL-cholesterol,
      triglycerides, bilirubin and serum activity of aminotransferases) and selected
      indices of left ventricular heart function were evaluated as intragroup
      differences using Student's paired t test. Afterwards the body mass index was
      compared. Statistically significant decrease of systolic arterial pressure after
      60 days of therapy was revealed and it concerned both diurnal period and sleep
      time and during whole 24 hours. During treatment with losartan mean creatinine
      serum level was increased and the serum level of bilirubin was decreased in serum
      after 10 days of therapy. No significant changes were noted in any other
      laboratory parameters. After 30 and 60 days of treatment with potassium losartan
      thickness of interventricular septum end-diastole (IVS-D) diminished and E/A
      ratio (transmitral flow during early ventricular diastole to peak velocity of
      late filling) augmented statistically significantly after 30 days of treatment.
      In addition body mass index was increased after 10 days of therapy with losartan
      when compared with this index at the entry. This study confirmed profitable
      antihypertensive losartan effect as significant decrease of systolic blood
      pressure and demonstrated improve diastolic function of left ventricle during
      therapy in patients with mild or moderate essential hypertension.

PMID- 11993409
TI  - [Bone tissue metabolism in systematic lupus erythematosus patients treated with
      glucocorticosteroids].
AB  - The present study has been undertaken to evaluate bone turn-over in patients with
      systemic lupus erythematosus (SLE) treated with glucocorticosteroids. Thirty
      eight patients with definite SLE has been investigated. The following parameters
      have been determinated. Some proinflammatory cytokine: interleukin-IL-1 alpha (IL
      1 alpha), interleukin-IL-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha),
      granulocyte-macrophage colony stimulating factor (GM-CSF) and some biochemical
      markers of osteoporosis: osteocalcin (BGP), alkaline phosphatase-bone formation
      (AP-B), procollagen type I carboxyterminal propeptide (PICP), carboxyterminal
      telopeptides of type I collagen (CTx) deoxypyridinoline (Dpd) and
      calcium/creatinin ratio have been determined. The forearm densitometry
      measurement was performed in all patients. We did not notice statistically
      significant decrease in bone mineral content and bone mineral density in spite of
      long term glucocorticosteroids treatment. Based on statistically significant
      correlation between carboxyterminal telopeptides of type I collagen (CTx) and
      calcium/creatinin ratio we observed increased bone resorption in analysed group
      of patients.

PMID- 11993410
TI  - [Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly
      obese women].
AB  - Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which
      may be involved in the increased incidence of atherosclerosis, arterial
      hypertension and non-insulin-dependent diabetes mellitus. The aim of the study
      was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL
      cholesterol, triglycerides (TG), products of cholesterol peroxidation-
      oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese
      women without coexisting diseases. The study was performed in 11 morbidly obese
      women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31
      kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs.
      0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs.
      41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/-
      199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level
      (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control
      group, while there were no significant differences between the two groups in
      concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG)
      ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p <
      0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p <
      0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover,
      concentration of 7-K correlated positively with the level of HDL (r = 0.54; p <
      0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there
      are disturbances in cholesterol peroxidation processes, with the rise in
      oxysterol levels and the decrease in vitamin E concentration in lipoproteins,
      which may be involved in the increased incidence of cardiovascular diseases in
      morbidly obese women.

PMID- 11993411
TI  - [Taking history in diagnosing coronary artery disease in the 21st century-
      wasting time or a valuable diagnostic tool?].
AB  - The relation of chest pain characteristics and other features of the history of
      disease to coronary angiograms was assessed in 551 patients with chest pain
      regarded as definite or probable stable angina pectoris. A standardised
      questionnaire was used to record demographic details and chest pain
      characteristics of interviewed patients. The differentiation between typical,
      atypical or nonanginal pain was based on classification proposed by Diamond. The
      indications for catheterization in each patient were determined at the discretion
      of the attending physician. All patients underwent diagnostic coronary
      angiography (clinically important coronary artery disease was defined as > 50 per
      cent narrowing of the diameter of at least one major vessel or > or = 50 per cent
      of the left main coronary artery). CONCLUSION: Chest pain characteristics remains
      an effective tool for estimating probability of coronary artery disease.

PMID- 11993412
TI  - [Interferon alpha--treatment predictive response factors in group of adults
      patients with chronic hepatitis C].
AB  - INTRODUCTION: Chronic hepatitis C (CHC) is a serious clinical problem. Serious
      sequelae of the disease such as liver cirrhosis and hepatocellular cancer warrant
      the search for efficacious therapeutic methods. It is assumed that some initial
      clinical and laboratory data may predict the therapeutic response. However,
      before they can be used in clinical practice, objective evaluation of their value
      is to be performed. AIM OF THE STUDY: Evaluation of IFN-alpha efficacy in
      treatment of patients with chronic hepatitis C. Evaluation of factors predictive
      for results of treatment (therapeutic response) in patients with chronic
      hepatitis C treated with IFN alpha2b. Evaluation of cumulative prognostic value
      of the significant features. MATERIAL AND METHODS: Fifty four adult patients with
      chronic hepatitis C were treated with IFN-alpha for 6 months. Follow up was
      continued for 18 months after the end of treatment period. In the studied group,
      19 clinical, biochemical and histologic features were the subjects of statistical
      analysis. RESULTS AND CONCLUSIONS: In 18.5% of patients the therapeutic response
      on IFN-alpha2b therapy was sustained, in 48.2% the response was transitory. In
      the remaining 33.3% of patients no therapeutic response were achieved.
      Discriminatory analysis revealed that duration of HCV infection, alcalic
      phosphatase activity in serum, histologic activity index, extensiveness of
      inflammation and biliary canaliculus proliferation in liver biopsy specimen
      before the IFN alpha2b treatment, are useful features predictive for the results
      of treatment. The cumulative prognostic value of these features in patients with
      chronic hepatitis C is 69%.

PMID- 11993413
TI  - [Evaluation of persistence of IFN-alpha treatment response in chronic hepatitis C
      patients according with HCV-RNA presence in PBMC].
AB  - BACKGROUND: The current criterion of cure of chronic hepatitis C (CHC) is the
      absence of HCV-RNA in hepatocytes and peripheral blood mononuclear cells (PBMC),
      as these cells are considered for the place of protracted viral replication.
      PURPOSE: Evaluation of HCV-RNA presence in serum, freshly isolated PBMC and
      cultured PBMC, taken from patients responding to interferon alfa2b therapy, after
      42 months of follow-up. Fifty four adults with CHC was treated with interferon
      alfa-2b (IFN-alpha 2b). Evaluation of HCV-RNA presence in serum were performed
      using RT-PCR method, before the therapy, and after 6 and 18 months of follow-up.
      All patients received interferon alpha-2b for 6 months. After 18 months of follow
      up, results of treatment (ALT activity and presence of HCV-RNA in serum) were
      retrospectively analyzed. In 10 of 54 patients (18.5%) normalization of ALT
      activity and negativization of HCV-RNA in serum were observed. After 42 months of
      follow-up, in these 10 patients, the presence of HCV-RNA in serum, in freshly
      isolated PBMC and cultured PBMC, were evaluated. RESULTS: After 42 months of
      follow-up, HCV-RNA was not found in serum of any patient. In 3 of 10 patients HCV
      RNA was present in freshly isolated PBMC. After 3-day-culture of PBMC, HCV-RNA
      was found in another patient. After 6 days of culture, results of RT-PCR test
      were negative in all cases. CONCLUSIONS: Absence of HCV-RNA in serum as well as
      in freshly isolated PBMC after 42 months of follow-up after the treatment of CHC,
      is not synonymous with eradication of virus. Three-day-culture of PBMC may be a
      valuable method, allowing for detection of subtreshold amounts of HCV. Longer, 6
      day-culture seems to be invaluable diagnostically.

PMID- 11993414
TI  - [Recurrent disseminated intravascular coagulation in the course of
      gastrointestinal stromal tumor (GIST)].
AB  - The objective of this paper was the description of a case of 68-year old male
      patient with epithelioid gastrointestinal stromal tumor (GIST). Disseminated
      intravascular coagulation syndrome (DIC) as the first and predominant revealed
      symptom of disease was observed. The final diagnosis was performed using the
      specific immunohistochemic and ultrastructural assays. The diagnostic and
      therapeutic difficulties were presented in discussion.

PMID- 11993415
TI  - [Intraalveolar hemorrhage as a cause of acute respiratory failure in catastrophic
      antiphospholipid syndrome].
AB  - We report the case of a catastrophic antiphospholipid syndrome (CAPS), which
      developed without a known cause in a 38-year old man. Primary antiphospholipid
      syndrome was diagnosed one year earlier. Clinical manifestations of CAPS were
      dominated by diffuse intraalveolar haemorrhage leading to acute respiratory
      failure and renal failure. Syndrome of multiorgan failure developed despite the
      treatment with plasmapheresis, high doses of glycocorticosteroids, an intravenous
      gammaglobulins. The patient died 6 weeks after the admission.

PMID- 11993416
TI  - [Mixed cryoglobulinemia].

PMID- 11993417
TI  - [Cyclooxygenases, structure, biological functions and the role in inflammation
      processes].

PMID- 11993418
TI  - [Cigarette smoking--the defined risk factor of ophthalmopathy in Grave's
      disease].

PMID- 11993419
TI  - [Extraesophageal symptoms of gastroesophageal reflux disease].

PMID- 11993420
TI  - [The Third Congress of the European Federation of Internal Medicine, Edinburgh,
      May 9-12, 2001].

PMID- 11993421
TI  - Emergency department personnel use seatbelts almost all the time: what do they
      know that average Delawareans don't?
AB  - A survey was sent to each emergency department in Delaware and each county
      Emergency Medical Service (EMS) Advanced Life Support (paramedic) service asking
      seven questions on risk-taking behavior. Within the survey were the following
      four questions regarding seatbelt use: a) Do you wear a seatbelt while driving?
      b) Do you require others in your car to wear seatbelts? c) When you are a
      passenger in a car, do you wear a seatbelt? d) Has the seatbelt law in Delaware
      impacted your seatbelt use? The three possible responses were "never,"
      "sometimes," and "always." The remaining three questions were confouders and
      asked about cigarette smoking and driving under the influence of alcohol. Replies
      were divided into the following job categories: 1) emergency physician (EP),
      emergency department (ED) physician assistant (PA) or nurse practitioner (NP), 2)
      emergency nurse, 3) paramedic, or 4) ED clerk, respiratory therapist (RT), or
      other emergency support personnel. A total of 313 surveys was returned by 78
      physicians, NPs and PAs; 115 paramedics; and 115 clerks, RTs, and other support
      personnel. Overall, 86 percent of respondent stated that they always wear
      seatbelts with 99 percent of EPs/PAs and NPs responding always. Overall, 83
      percent stated that they require others to wear seatbelts in their automobiles.
      Eighty-four percent wear seatbelts while a passenger in someone else's car. The
      physician, PA, and NP group had the greatest "always" response rate as compared
      to the other groups.

PMID- 11993422
TI  - Giving support when giving the diagnosis of cancer.

PMID- 11993423
TI  - [Osteoporosis, a real public health problem].

PMID- 11993424
TI  - [Public health. Epidemiology of osteoporosis].

PMID- 11993425
TI  - [Nursing care. Diagnosis and treatment of osteoporosis in the elderly].

PMID- 11993426
TI  - [Public health. Prevention of osteoporosis in the elderly].

PMID- 11993427
TI  - [Music therapy in nursing homes].

PMID- 11993428
TI  - [The dietician, an actor in the care in the geriatric service].

PMID- 11993429
TI  - [Ergonomics in the gerontology service].

PMID- 11993430
TI  - [The elderly and automobile driving: analysis and reflection on the emergence of
      a social phenomenon].

PMID- 11993431
TI  - [A beautician in the hospital].

PMID- 11993432
TI  - [Protection or unprotection?].

PMID- 11993433
TI  - [Alzheimer's disease, persistent deficiencies in the management of patients].

PMID- 11993435
TI  - HHS announces Medicare premium and deductible rates for 2001,.

PMID- 11993434
TI  - [Metrorrhagia after 75 years old, only 10% are signs of a cancer].

PMID- 11993436
TI  - Coming back.

PMID- 11993437
TI  - Passed bucks.

PMID- 11993438
TI  - Drawing the curtain on the 'good old days'.

PMID- 11993439
TI  - Monitoring pulp vitality after transplantation of teeth with mature roots: a case
      report.
AB  - AIM: To initiate discussion on the value of routine root canal treatment for
      transplanted teeth. SUMMARY: Autotransplantation is an accepted treatment option
      to replace missing teeth. It is generally considered that revascularization of
      the pulp following such a procedure is more favourable in teeth with immature
      roots. In teeth with closed apices root canal treatment is considered necessary.
      This paper presents a case of pulp revascularization in a transplanted tooth with
      mature roots and casts doubt on whether root canal treatment is essential in such
      situations. An alternative treatment protocol is proposed. KEY LEARNING POINTS: *
      Following transplantation original pulp tissue may survive the operation. * Teeth
      with obliterated pulp space do not become necrotic more often than those without
      obliteration. * Monitoring the tooth is an acceptable alternative to automatic
      root canal treatment for transplanted teeth. * Root canal treatment should be
      undertaken only upon occurrence of pathological signs.

PMID- 11993440
TI  - Localized alveolar bone necrosis following the use of an arsenical paste: a case
      report.
AB  - AIM: To describe some toxic effects of arsenic trioxide in the mouth, to condemn
      its continued use, and present a case in which a tooth was preserved despite
      significant bony destruction. SUMMARY: A case is presented in which severe
      alveolar bone necrosis resulted from leak-age of an arsenical devitalization
      paste into the periodontium. The tooth was root canal treated before root
      amputation, and restored with a cuspal coverage restoration. The tooth was
      observed to be symptomless and functional at the one-year follow-up. KEY LEARNING
      POINTS: * Arsenic and its compounds have no place in contemporary endodontics. *
      Dentists should protect their patients by avoiding the use of arsenic-containing
      materials and refusing to use products whose constituents are not known. *
      Localized bone necrosis may not require tooth extraction. Depending on the
      severity of the case, the tooth may be preserved by a combination of endodontic,
      periodontal,prosthodontic and maintenance therapies.

PMID- 11993441
TI  - Non-surgical root canal treatment of dens invaginatus type 2 in a maxillary
      lateral incisor.
AB  - AIM: To describe the clinical management of an unusual dens invaginatus type 2.
      SUMMARY: A case of dens invaginatus in a maxillary lateral incisor with a
      periapical lesion is reported. The patient presented with pain and localized
      swelling. Despite the complex anatomy and diagnosis of dens invaginatus, non
      surgical root canal treatment was performed successfully. KEY LEARNING POINTS: *
      Dens invaginatus may be presented in many forms, and the aetiology of this
      phenomenon is not fully understood. * Due to abnormal anatomical configuration,
      dens invaginatus presents technical difficulties in its clinical management. *
      Non-surgical root canal treatment can be performed successfully.

PMID- 11993442
TI  - Statin stories.

PMID- 11993443
TI  - Lipid lowering.

PMID- 11993444
TI  - Getting an extension.

PMID- 11993445
TI  - Angina, diabetes and SUR.

PMID- 11993446
TI  - National Service Frameworks--a work in several parts.

PMID- 11993447
TI  - Coming together.

PMID- 11993448
TI  - The hot and the classic.

PMID- 11993449
TI  - [Ephedrine psychosis reconsidered].

PMID- 11993450
TI  - Improving the odds against hypertension.

PMID- 11993452
TI  - Beliefs about and responses to childhood ear infections: a study of parents in
      eastern North Carolina.
AB  - Middle ear infection, also known as otitis media (OM), is a major public health
      problem among American children. Although clinical and epidemiological aspects of
      OM have been intensely studied, cultural factors that may be contributing to the
      problem of OM have received less attention. This article presents findings from
      an ethnographic study exploring beliefs about OM and responses to the illness
      among parents from eastern North Carolina. In-depth interviews were conducted
      with a convenience sample of nine mothers in order to learn more about parents'
      explanatory models of OM, the source of their beliefs, and how they respond to
      the illness. A survey instrument based on their statements was then constructed
      and administered to a convenience sample of 79 parents. The survey consisted of
      belief statements about OM, as well as questions pertaining to sources of
      beliefs, the home management of the disease, and the effects of the illness on
      families. A cultural consensus analysis of responses to belief statements
      indicates that parents shared a common model of OM. Beliefs about risks,
      symptoms, and causes of OM were similar to the current biomedical model of the
      illness, but their divergent beliefs about the diagnosis, prognosis and treatment
      of OM could lead to unnecessary use of health care services. Clinicians, family,
      and friends were reported to be important sources of information about OM.
      Parents also reported using similar home management strategies and care seeking
      behaviors to minimize the impact of the illness on their children and families.
      While these findings need to be replicated in studies with larger, more
      representative samples, this study suggest that ethnographic approaches may
      provide new insights into the cultural dimension of the problem of OM.

PMID- 11993453
TI  - Tenascin in the human intervertebral disc: alterations with aging and disc
      degeneration.
AB  - Our objective for this study was to determine the presence and distribution of
      tenascin in the human intervertebral disc. The tenascins are a family of
      extracellular matrix proteins with repeated structural domains homologous to
      epidermal growth factor, fibronectin type III and the fibrinogens. Little is
      known about the presence of this protein in the disc. Ten normal human discs
      donated from subjects newborn to 15 years old, 10 control discs from adult donors
      aged 24-41 years, and 11 surgical disc specimens from patients aged 26-76 years
      were examined for immunolocalization of tenascin. In young discs, tenascin was
      localized throughout the annulus; in the nucleus, localization was confined to
      pericellular matrix. In adult control and degenerating disc specimens, tenascin
      in the annulus was localized primarily in pericellular matrix regions encircling
      either single cells or clusters of disc cells; in rare instances localization was
      more diffuse in the intraterritorial matrix. In young, healthy disc, tenascin was
      abundant throughout the annulus. In contrast, degenerating discs in adults showed
      a localization restricted to the pericellular, and rarely, more restricted
      intraterritorial matrix. These observations indicate that changes in the amount
      and distribution of tenascin may have a role in disc aging and degeneration,
      possibly by modulating fibronectin-disc-cell interactions, and causing
      alterations in the shape of disc cells.

PMID- 11993454
TI  - [Tumor markers useful for diagnosis and monitoring of lung neoplasm].
AB  - Serum tumour markers may be helpful in early diagnosis of lung cancer, in the
      initial assessment of the extent of the disease, and in monitoring of the tumour
      growth or tumour volume reduction, once cancer has been diagnosed and treatment
      started. Recent studies have focused especially--cytokines as a new group of
      tumour markers.

PMID- 11993455
TI  - [An alherce (magical recipe) contained in the Miscelaneo de Salomon].
AB  - We offer the Arabic text and a translation with comments of an alherce contained
      in a manuscript entitled Miscelaneo de Salomon, which was found in Ocana, Toledo.
      This book belonged to an Alfaqui of the area, who used it to provide spiritual
      and physical support to the Mudejars with whom he lived. The alherce presented
      here contains invocations and spells and was used for medical and various other
      purposes.

PMID- 11993456
TI  - [Arab surgery and cancer: definitions and treatments].
AB  - The present paper presents the study of a set of cancers collected by medieval
      doctors, especially Arabic surgeons, in order to identify their knowledge about
      carcinoma, how they defined the disease and, most importantly, what type of
      treatment they applied. The paper is organised in three sections: in section 1,
      we focus on the terminology used to refer to carcinoma. In section 2, we offer a
      description of the symptoms specific to each type of cancer. Finally, in section
      3, we describe the surgical and pharmacological treatments, followed by diet
      related remedies. We analysed texts by al-Zahrawi, Ibn Sina, Ibn al-Quff and al
      Safra.

PMID- 11993457
TI  - [Medicine versus surgery: the treatment of eye diseases in the works of Abulcasis
      and Avenzoar].
AB  - Although they start from generically distinct positions-- from the standpoint of
      a surgeon in the case of Abulcasis (11th Century), and from that of a physician
      in the case of Abenzoar (12th Century) - we attempt to show that the latter made
      an important, documented and unsuspected contribution to the surgical therapy of
      diseases of the eye. Naturally, Abenzoar discusses the surgical approach after
      first recommending other pharmacological and dietary remedies. To this end, we
      studied the chapters dedicated to the diseases of the eye in Kitab al-tasrif li
      man 'ayiza an al-ta 'lif: The Book of the arrangement [of medical science] for
      those who are unaware of it by Abulcasis, and in Kitab al-taysir fi l-mudawat wa
      l-tadbir. The Book of the Simplification of Medication and Diet by Abenzoar. In
      support of our hypothesis, we make some observations on the introduction and use
      of the cataract removal technique in al-Andalus.

PMID- 11993458
TI  - [Therapeutic use of aromatic substances in al-Andalus ].
AB  - Aromatic substances were used for therapeutic purposes in the ancient Arabic
      world, as they were in other contemporary and earlier cultures. By the Tenth
      Century, the Oriental Islamic culture had developed a solid corpus on aromatic
      substances that were selected for that purpose. This paper is an introduction to
      the knowledge of these substances that had been attained in al-Andalus in the
      Eleventh Century (considered the "Golden Age" of Andalusian pharmacology), based
      on the comparative study of the Kitab yawahir al-tib al-mufrada, by Ibn Masawayh,
      and the Kitah al-adwiya al-mufrada, by Ibn Wafid.

PMID- 11993459
TI  - The use of high field/frequency EPR in studies of radical and metal sites in
      proteins and small inorganic models.
AB  - Low temperature electron paramagnetic resonance (EPR) spectroscopy with
      frequencies between 95 and 345 GHz and magnetic fields up to 12 T have been used
      to study radicals and metal sites in proteins and small inorganic model
      complexes. We have studied radicals, Fe, Cu and Mn containing proteins. For S =
      1/2 systems, the high frequency method can resolve the g-value anisotropy. It was
      used in mouse ribonucleotide reductase (RNR) to show the presence of a hydrogen
      bond to the tyrosyl radical oxygen. At 285 GHz the type 2 Cu(II) signal in the
      complex enzyme laccase is clearly resolved from the Hg(II) containing laccase
      peroxide adduct. For simple metal sites, the systems over S = 1/2 can be
      described by the spin Hamiltonian: H(S) = BgS + D[Sz2 - S(S + 1)/3 + E/D (Sx2 -
      Sy2)]. From the high frequency EPR the D-value can be determined directly by, (I)
      shifts of g(eff) for half-integer spin systems with large D-values as observed at
      345 GHz on an Fe(II)-NO-EDTA complex, which is best described as S = 3/2 system
      with D = 11.5 cm(-1), E = 0.1 cm(-1) and gx = gy = gz = 2.0; (II) measuring the
      outermost signal, for systems with small D values, distant of (2S - 1) x absolute
      value(D) from the center of the spectrum as observed in S= 5/2 Fe(III)-EDTA. In
      Mn(II) substituted mouse RNR R2 protein the weakly interacting Mn(II) at X-band
      could be observed as decoupled Mn(II) at 285 GHz.

PMID- 11993460
TI  - High-frequency and -field electron paramagnetic resonance of high-spin
      manganese(III) in tetrapyrrole complexes.
AB  - High-field and -frequency electron paramagnetic resonance (HFEPR) spectroscopy
      has been used to study three complexes of high spin Manganese(III), 3d4, S = 2.
      The complexes studied were tetraphenylporphyrinatomanganese(III) chloride
      (MnTPPCI), phthalocyanatomanganese(III) chloride (MnPcCl), and (8,12-diethyl
      2,3,7,13,17,18-hexamethylcorrolato)manganese(III) (MnCor). We demonstrate the
      ability to obtain both field-oriented (single-crystal like) spectra and true
      powder pattern HFEPR spectra of solid samples. The latter are obtained by
      immobilizing the powder, either in an n-eicosane mull or KBr pellet. We can also
      obtain frozen solution HFEPR spectra with good signal-to-noise, and yielding the
      expected true powder pattern. Frozen solution spectra are described for MnTPPCl
      in 2:3 (v/v) toluene/CH2Cl2 solution and for MnCor in neat pyridine (py)
      solution. All of the HFEPR spectra have been fully analyzed using spectral
      simulation software and a complete set of spin Hamiltonian parameters has been
      determined for each complex in each medium. Both porphyrinic complexes (MnTPPCl
      and MnPcCl) are rigorously axial systems, with similar axial zero-field splitting
      (zfs): D approximately -2.3 cm(-1), and g values quite close to 2.00. In
      contrast, the corrole complex, MnCor, exhibits slightly larger magnitude, rhombic
      zfs: D approximtely -2.6 cm(-1), absolute value(E) approximately 0.015 cm(-1),
      also with g values quite close to 2.00. These results are discussed in terms of
      the molecular structures of these complexes and their electronic structure. We
      propose that there is a significant mixing of the triplet (S = 1) excited state
      with the quintet (S= 2) ground state in Mn(III) complexes with porphyrinic
      ligands, which is even more pronounced for corroles.

PMID- 11993461
TI  - Characterization of the surface interacting ability of carbon black by means of
      electron paramagnetic resonance analysis of adsorbed Cu2+, supported by surface
      analysis and atomic absorption.
AB  - Electron paramagnetic resonance (EPR) has been used to investigate the adsorption
      capability and the surface interacting ability towards Cu(II) solutions (CuCl2,
      Cu(NO3)2, CuSO4 in water or ethanol) of various carbon blacks, both graphitized
      and ungraphitized, selected on the basis of the surface area, namely, Carbograph1
      (area = 100 m2/g), Carbograph4 (area = 210 m2/g), and Carbograph5 (area = 560
      m2/g), which were indicated as C1g, C4g, C5g (g = graphitized), and C1ng, C4ng,
      C5ng (ng = ungraphitized). The EPR analysis was supported by surface analysis,
      for evaluating the surface area, the pore volume and the porosity, and by atomic
      absorption to obtain the adsorbed Cu(II) amounts. Graphitization provokes a
      decrease in surface area, but C1g, at low surface area, showed a unexpected
      increase of the adsorption ability ascribed to the formation of new surface
      porosity closed by graphite layers. The carbon samples showed a broad unresolved
      EPR signal due to mobile unpaired electrons in the carbon matrix. Graphitized
      samples presented a narrower signal than ungraphitized samples, which increases
      in width with the increase in surface area (with the exception of C5ng due to the
      high exposition of the wide surface to oxydizing external agents) and upon
      prolonged thermal treatment. The signal intensity of the carbon paramagnetic
      centers decreases upon Cu(II) adsorption. Computer aided analysis of the EPR
      spectra of the solids after Cu(II) adsorption allowed to extract structural
      information on the Cu-surface site complexes. The Cu2+ ions coordinated with
      surface polar sites, mainly oxygenated. Adsorption depends on the different
      Cu(II) salts, caused by the salt solubility and the interacting ability of the
      counter-ion. In several cases the solutions concentrated in the carbon porosity
      leading to precipitation of the salt. Ethanol solutions are more adsorbed at the
      carbon surface than water solutions; Cu(II) partially retains its solvation shell
      and partially presents electron transfer to the carbon surface. Adsorption is
      favored to ungraphitized carbons with respect to the graphitized ones due to both
      the higher surface area, and the higher hydrophilicity of the surface. In
      summary, these carbon powders, widely used for chromatographic applications, show
      an adsorption capability towards Cu(II) solutions higher than expected due to
      both a definite porosity, and the presence of polar groups which are not
      eliminated with chemical surface treatments.

PMID- 11993462
TI  - An ESR study of titanium-silicalite in presence of H2O2.
AB  - The interaction of H2O2 with TS-1 has been investigated by the ESR technique. A
      well manufactured TS-1 has been considered, where the presence of extra
      structural titanium can be excluded. The two main signals observed are attributed
      to oxygen radical species co-ordinated on structural titanium sites, and the
      relevant effect of water presence in the paramagnetic complex is discussed. A
      comparison is performed with O2-/Ti species in TS-1 obtained by reduction/re
      oxidation procedures of Ti(IV). Moreover, some possible structural configurations
      of the paramagnetic sites are proposed, for two of which ab initio calculation
      yield g(z)-values quite close to the experimental ones.

PMID- 11993463
TI  - EPR and electronic spectral studies of bis(dihalcogenocarbamato)copper(II)
      solvent interactions.
AB  - The interaction of bis(diethyldithiocarbamato)copper(II), Cu(Et2dtc)2, and
      bis(diethyldiselenocarbamato)copper(II), Cu(Et2dsc)2, complexes with solvents is
      studied by EPR and electronic spectroscopy. The solvents used are CCl4, CHCl3,
      CH2Cl2, C6H5 x CH3, DMFA and DMSO. It is found that Cu(Et2dsc)2 is destroyed in a
      first order reaction in CCl4 with an activation energy of 5.2 kcal/mol. The other
      complex, Cu(Et2dtc)2, is only destroyed in DMSO. The observed effects and
      reaction pathways are discussed in terms of solute-solvent donor-acceptor
      interactions taking into account the differences in the electronic structures of
      both complexes.

PMID- 11993464
TI  - Charge-transfer photochemistry of the ternary complex (dithio-diseleno
      carbamato)copper(II).
AB  - Photolysis of the ternary system consisting of diethyldithiocarbamate (Et2dtc),
      diethyldiselenocarbamate (Et2dsc) and copper(II) (1:1:1) has been studied in
      isobutylmethylketone (IBMK), toluene, chloromethane and chloromethane/ROH
      solutions (chloromethane = CCl4, CHCl3 or CH2Cl2 and ROH = EtOH or i-PrOH). The
      results obtained by EPR techniques and UV-Vis data indicate that a homolytic Cu-S
      bond cleavage involving the dithiocarbamate (dtc) ligand appears as the primary
      photo-process in Cu(Et2dtc)(Et2dsc) photolysis. Further conversion of the primary
      photoproduct Cu(I)(Et2dsc) is discussed in terms of a specific interaction with
      the solvent. In chloromethanes and chloromethane/ROH Cu(I)(Et2dsc) is oxidised by
      the solvent to give the corresponding paramagnetic mixed-ligand Cu(II)(Et2dsc)Cl
      complex and/or its chloride-bridged and EPR silent dimer Cu2(Et2dsc)2Cl2. The
      formation of the monomeric species occurs through a co-ordination of the alcohol
      molecule in the xy plane of the complex. Because of its co-ordination inertness,
      toluene poorly stabilises the primary photoproduct Cu(I)(Et2dsc), thus providing
      an effective primary recombination process and lower efficiency of
      Cu(Et2dtc)(Et2dsc) photolysis. The formation of the bis-solvated mixed-ligand
      complex Cu(II)(Et2dsc)+ in IBMK is also discussed.

PMID- 11993465
TI  - Effect of solute-co-ordinating solvent interactions and temperature on the EPR
      and electronic spectra of bis(dithiophosphato)copper(II).
AB  - The self-redox reaction proceeding between two molecules of the complex
      bis(disubstituted-dithiophosphato)copper(II), CuII(R2-dtp)2, is studied by EPR
      and UV-VIS spectroscopy in DMFA, DMSO and pyridine. The effect of temperature and
      disulphide concentration in the solutions is also evaluated. The EPR spectra show
      that the g-values of CuII(R2-dtp)2 increase when it is dissolved in co-ordinating
      solvents, whereas the copper hyperfine splitting decreases compared to the
      corresponding values in non-co-ordinating solvents. Under the same conditions, a
      hypsochromic shift is observed in the maximal absorption at 420 nm of the
      electronic spectra which corresponds to the ligand-to-metal charge-transfer
      (LMCT) transition of the complex. The results are explained with the formation of
      axial or equatorial adducts between CuII(R2-dtp)2 and the co-ordinating solvents
      used. On the other hand, the molar absorptivity of the LMCT band and the
      intensity of the EPR spectrum increase strongly with the nature of the used co
      ordinating solvent, the time after dissolution and the quantity of added
      disulphide. Both also depend on the size and shape of remote ligand substituents
      and they increase in the order Me < Et < i-Pr. Beer's law is not obeyed
      immediately after dissolution of copper bis-dithiophosphate complexes. However,
      after standing for 24 h in the dark, DMFA solutions exhibit linear
      absorption/concentration dependence with approximately 70% higher molar
      absorptivity. An additional increase of the LMCT band and EPR intensity is found
      after heating the solution up to 50 degrees C for a short time, as well as after
      addition of the corresponding disulphide of dithiophosphate [(RO)2P(S)S
      S(S)P(RO)2] to the CuII(R2-dtp)2 solution. As a result, the molar absorptivity
      value at the maximum of the LMCT band of Cu[(i-PrO)2-dtp]2 increases from 7.9 x
      10(3) m(-1) dm3 cm(-1) immediately after dissolution to 2.9 x 10(4) m(-1) dm3 cm(
      1). In DMSO and pyridine, the intensity of both the EPR signal and LMCT band of
      CuII(R2-dtp)2 continuously decrease after the preparation of the solutions. A
      small increase is only observed immediately after the addition of the
      corresponding disulphide of dithiophosphate. While DMFA forms stable adducts with
      Cu[(i-PrO)2-dtp]2, adduct formation with DMSO and pyridine destroys the initial
      complex.

PMID- 11993466
TI  - Thermodynamics of ligand exchange reactions between
      bis(dithiocarbamato)copper(II) and copper(II) salts. An EPR study.
AB  - EPR spectroscopy was chosen to investigate the ligand exchange reactions between
      copper(II) bis(dithiocarbamate), Cu(dtc)2, and copper(II) salts which proceeds
      with the formation of mixed-ligand complexes of the type Cu(dtc)X, where X = Cl,
      NO3, ClO4. Large concentrations of 1:1 mixed-ligand complexes of this type are
      obtained as indicated by the EPR spectra of acetone, CHCl3/EtOH, CHCl3/i-PrOH,
      CCl4/EtOH and CCl4/i-PrOH, solutions of Cu(dtc)2 and the appropriate copper(II)
      salt CuCl2, Cu(NO3)2 or Cu(ClO4)2. Double integration of Cu(dtc)2 EPR signals
      obtained at temperatures between 240 and 310 K affords the calculation of the
      equilibrium constant (K) of the reaction: Cu(dtc)2 + CuX2 <==> 2 Cu(dtc)X in all
      solvents as a function of T. From the values of K the stability constant beta of
      the mixed-ligand complexes has been derived. The error associated with the
      calculated stability constant is +/- 10%. Thermodynamic parameters (deltaH0,
      deltaG0 and deltaS0) are determined from the temperature dependence of K as
      measured by EPR spectroscopy.

PMID- 11993467
TI  - 2D-hyperfine sublevel correlation spectroscopy of tyrosyl radicals.
AB  - Hyperfine sublevel correlation (HYSCORE) spectroscopy has been used to study the
      tyrosyl radicals in Photosystem II and bovine liver catalase. The HYSCORE data
      allow a complete resolution of all the 1H hyperfine tensors of these radicals.
      The present work shows that the proper analysis of the HYSCORE data allows the
      complete assignment of the 1H-hyperfine tensors in tyrosine radicals and this
      offers an alternative experimental tool relative to ENDOR.

PMID- 11993468
TI  - Electronic structure of the lowest excited triplet state of 5,12
      naphthacenequinone.
AB  - Continuous-wave time-resolved EPR (cw-TREPR) and pulsed electron nuclear double
      resonance (ENDOR) studies have been carried out to clarify the electronic
      structure of the lowest excited triplet (Tl) state of 5,12-naphthacenequinone
      (5,12-NpQ) as well as 1,4-anthraquinone (1,4-AQ) and 6,13-pentacenequinone (6,13
      PeQ). The Tl energy level and the D value of the zero-field splitting (ZFS)
      parameters only slightly decreased with the increasing pi-conjugated system. The
      Tl states of these linear para-acenequinones were assigned to the pi pi*
      character. In triplet 5,12-naphthacenequinone, more than 80% of the unpaired
      electron spins are localized on the naphthalene aromatic sub-system.

PMID- 11993469
TI  - A radiolabelling study of radicals derived from benzene, toluene and benzaldehyde
      sorbed in model environmental carbon.
AB  - Radiolabelled free radicals were formed by the addition of muonium--a radioactive
      hydrogen atom with a positive muon as its nucleus--to benzene, toluene and
      benzaldehyde, as sorbed in porous carbon. The activation parameters associated
      with their reorientational motion were measured using longitudinal-field muon
      spin relaxation (LF-MuSRx). Two distinct sorbed fractions were detected in each
      sample, characterised by molecular reorientational activation energies of
      5.9/25.8 kJ/mol for benzene, 2.5/5.9 kJ/mol for toluene and 2.9/11.5 kJ/mol for
      benzaldehyde.

PMID- 11993470
TI  - Dimerization of organic free radicals in solution. 1. Temperature dependent
      measurements.
AB  - Dimerization enthalpies and equilibrium constants have been determined for the
      radical anion of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), the radical
      cations of N,N,N',N'-tetramethyl-p-phenylenediamine, N,N-dimethyl-p
      phenylenediamine, 2,3,5,6-tetramethyl-p-phenylenediamine, N,N,N',N'-tetraethyl-p
      phenylenediamine, N,N-diethyl-p-phenylenediamine and N,N,N'-trimethyl-p
      phenylenediamine. Neutral radicals investigated are 2,2,6,6-tetramethylpiperidine
      1-oxyl (TEMPO) and galvinoxyl. Solvent used was acetone, EtOH/Et2O-mixture (2:1
      volume), propionitrile/butyronitrile-mixture (1:1 M) and dichloromethane.
      Measured dimerization enthalpies deltaHdim vary from -72.1 to -16.6 k/mol.

PMID- 11993471
TI  - In vivo copper-mediated free radical production: an ESR spin-trapping study.
AB  - Copper has been suggested to facilitate oxidative tissue injury through a free
      radical-mediated pathway analogous to the Fenton reaction. By applying the
      electron spin resonance (ESR) spin-trapping technique, evidence for hydroxyl
      radical formation in vivo was obtained in rats treated simultaneously with copper
      and ascorbic acid or paraquat. A secondary radical spin-trapping technique was
      used in which the hydroxyl radical formed the methyl radical upon reaction with
      dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as
      its adduct with the spin trap phenyl-N-t-butyl- nitrone (PBN). In contrast, lipid
      derived radical was detected in vivo in copper-challenged, vitamin E and selenium
      deficient rats. These findings support the proposal that dietary selenium and
      vitamin E can protect against lipid peroxidation and copper toxicity. Since
      copper excreted into the bile from treated animals is expected to be maintained
      in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that
      would redox-stablilize it in the Cu(I) state was used to prevent ex vivo redox
      chemistry. Bile samples were collected directly into solutions of
      bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a
      Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts
      generated ex vivo could be mistaken for radical adducts produced in vivo and
      excreted into the bile.

PMID- 11993472
TI  - Molecular organization and dynamics of micellar phase of polyelectrolyte
      surfactant complexes: ESR spin probe study.
AB  - Molecular dynamics and organization of the micellar phase of complexes of linear
      polyelectrolytes with ionogenic and non-ionogenic surfactants was studied by the
      ESR spin probe method. Complexes of polyacrylic acid (PAA) and sodium
      polystyrenesulfonate (PSS) with alkyltrimethylammonium bromides (ATAB), as well
      as complexes of poly-N,N'-dimethyldiallylammonium chloride (PDACL) with sodium
      dodecylsulfate (SDS) were studied. The micellar phase of such complexes is highly
      organized molecular system, molecular ordering of which near the polymeric chain
      is much higher than in the 'center' of the micelle, it depends on the polymer
      detergent interaction, flexibility of polymeric chain and length of carbonic part
      of the detergent molecule. Complexes of polymethacrylic acid (PMAA) with non
      ionic detergent (dodecyl-substituted polyethyleneglycol), show that the local
      mobility of surfactant in such complexes is significantly lower than in 'free'
      micelles and depends on the number of micellar particles participating in
      formation of complexes.

PMID- 11993473
TI  - On the application of electron paramagnetic resonance in the study of naturally
      occurring quinones and quinols.
AB  - From electron paramagnetic resonance (EPR) spectra of numerous semiquinone anion
      radicals we propose that the spin density distributions in benzo-, naphtho- and
      anthrasemiquinones are changed under the influence of various substituent in a
      comparable fashion, electron donating substituents having the opposite effect of
      withdrawing ones. These findings facilitate the work in obtaining correct
      assignments, further leading to safe identification of new radicals. Semiquinone
      anion radicals of para- and ortho-hydroquinones are demonstrated to exist at
      physiological pH in buffered solutions under continuous access to molecular
      oxygen. Reaction schemes are proposed for the formation of primary and tertiary
      radicals and hydroxylated products of ten quinols. From studies on crude plant
      extracts are three quinols, known as precursors in the biogenesis of chimaphilin,
      observed and identified in Chimaphila umbellata. Other studies demonstrate the
      power of using semiquinone radicals as chemotaxonomic markers.

PMID- 11993474
TI  - Novel EPR characterization of the antioxidant activity of tea leaves.
AB  - Electron paramagnetic resonance (EPR) spectroscopy is utilized to investigate
      several categories of green and black tea: Twining green tea (TGT), Chinese green
      tea (CGT), Red-labels black tea (RBT). Basically, two EPR signals from all the
      studied samples are observed: One of them is a very weak sharp EPR signal with
      deltaHpp approximately 10 G and g-factor = 2.00023 superimposed on the other
      broad signal with deltaHpp approximately 550 G and g-factor = 2.02489. The broad
      signal is a characteristic one of manganese(II) complex, while the sharp signal
      is related to a stable radical of aromatic origin exist in a powder condition.
      The feature of the manganese EPR signal is attributed to manganese(II) complex
      and reflected the molecular behavior of Mn(II) in the protein system of the
      natural leaves. The sharp signal, which is most probably due to a semiquinones
      radicals, is observed at room temperature and its intensity is remarkably
      affected by photo degradation of the studied samples. The intensity of
      manganese(II) EPR signal is found to be related to ageing and disintegration of
      the tea leaves. Moreover, direct relation between the relative intensity of the
      semiquinones radical signal and antioxidant activity of the studied samples was
      also correlated.

PMID- 11993475
TI  - The influence of additives on beer stability investigated by EPR spectroscopy.
AB  - In thermally-accelerated aging followed by EPR spectroscopy of beer samples of
      various stabilities, free radical 4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy
      (TEMPOL) was shown to be an effective indicator of the breakdown of a sample's
      stability, comparable to the commonly used spin trapping agent alpha-phenyl-N
      tert-butylnitrone (PBN). Both indicators were then employed to investigate the
      influence of additives on beer stability. The addition of L-ascorbic acid (ASC)
      to the beer samples accelerated the radical processes and a lower stability was
      found. DL-alpha-tocopherol (alpha-TOC) did not influence beer stability
      significantly (probably due to its limited solubility). Na2SO3, described as a
      very effective stabilizer in experiments with the PBN spin trap, was found not to
      be effective using the TEMPOL indicator. This is probably due to inhibition in
      the formation of spin adducts or their degradation by Na2SO3.

PMID- 11993476
TI  - Quantitative EPR study on free radicals in the natural polyphenols interacting
      with metal ions and other environmental pollutants.
AB  - Quantitative electron paramagnetic resonance (EPR) method was applied to
      characterise radicals stabilised in polyphenolic matrices of various biogenic
      materials: lichens, mosses, composts, soils, peats, brown coals and sewage sludge
      sediments. The investigations were carried out on raw materials and extracted
      fractions of humic acids (HA). General trends of g value and spin concentration
      changes were found. These parameters in lichens strongly depend on lichen species
      and air pollution. Determination of the g value and semiquinone spin
      concentration allows to assess degree of transformation of organic matter in
      compost, soil, peat and lignite. Application of gaseous ammonia as a base
      penetrating the organic matrices extends the possibilities and usefulness of the
      method. Interaction of metal ions with humic materials is illustrated by
      interaction of VO2+ ion with peat and lignite HA as well as demineralised (raw
      and carbonised) brown coal. Our investigations demonstrate that quantitative EPR
      is a rapid and effective monitoring method to study the influence of various
      environmental factors on substances containing polyphenolic matrices.

PMID- 11993477
TI  - New materials for ESR dosimetry.
AB  - New materials for electron spin resonance (ESR) dosimetry have been investigated
      with the aim to find systems more sensitive than L-alanine accepted as a standard
      for high dose determinations. Among the investigated systems ammonium tartrate, 2
      methylalanine, salts of formic acids and dithionates have been found to be more
      sensitive than alanine by a factor 2-10. The lower limit applies to tissue
      equivalent materials, while much higher sensitivities were obtained with formates
      and dithionates containing heavier atoms. The increased sensitivity was mainly
      attributed to suitable ESR properties of the room temperature stable radicals as
      regards spectral shape (narrow lines, little or no hyperfine structure) and
      microwave saturation properties (short relaxation times). The radical structures
      have when necessary been clarified by ENDOR spectroscopy, while the saturation
      properties have been screened by pulsed ESR measurements.

PMID- 11993478
TI  - Electron paramagnetic resonance of radicals induced in drugs and excipients by
      radiation or mechanical treatments.
AB  - Radiation as well as mechanical treatments induced in drugs and excipients
      radicals, which can be studied by electron paramagnetic resonance. A special
      attention is pointed about the use of electron paramagnetic resonance (EPR) to
      bring the proof whether or not a drug has been irradiated or not. We also discuss
      of other methods (thermoluminescence (TL), gas phase chromatography (GPC)) which
      can be used to bring the same proof in case of irradiated drugs, excipients and
      cosmetic products.

PMID- 11993479
TI  - Some recent multi-frequency electron paramagnetic resonance results on systems
      relevant for dosimetry and dating.
AB  - Electron Paramagnetic Resonance (EPR) applications like e.g. EPR dosimetry and
      dating, are usually performed at X-band frequencies because of practical reasons
      (cost, sample size, etc.). However, it is increasingly recognized that the
      radiation-induced EPR signals are strongly composite, what might affect dose/age
      estimates. A few recent examples from both the dosimetry and dating field,
      illustrating the problems, will be presented. The involved spectra are mainly due
      to carbonate-derived radicals (CO2-, CO3(3-), etc.). Measurements at higher
      microwave frequencies are often recommended to improve the insight into the
      spectra and/or the practical signal quantification. Recent results at Q- and W
      band frequencies will show that a multi-frequency approach indeed opens many
      interesting perspectives in this field but also that each frequency may have
      specific (dis)advantages depending on the EPR probe and application involved. The
      discussion will concern carbonate-containing apatite single crystals, shells,
      modern and fossil tooth enamel.

PMID- 11993480
TI  - Filling factor in a pulsed electron paramagnetic resonance experiment.
AB  - A definition and mathematical treatment to calculate the filling factor in a
      pulsed electron paramagnetic resonance (EPR) experiment are presented. The
      differences between filling factors in traditional, continuous wave (CW)-EPR
      experiments (eta), and in pulsed-EPR experiments (eta(p)), are discussed. We
      present some examples to demonstrate how eta(p) depends upon the particular pulse
      sequence and sample characteristics.

PMID- 11993481
TI  - SURF_ER--surface electron spin resonance (ESR) of the surface domain of large
      objects.
AB  - SURF_ER is a method for spectral and spatial electron spin resonance measurements
      on the surface of large objects which extension is only restricted by the width
      of the pole gap of the magnet and the homogeneity of the magnetic field and not
      by the cavity dimensions. The application of several techniques like SURF_ER for
      spectroscopic measurements, SURF_ERM for spatial scanning and SURF_ERI for
      spatial measurements of the depth of the surface region are discussed and
      represented for the skin of a human being as an example.

PMID- 11993482
TI  - FDA advisory panels recommend Lotronex be put back on market.

PMID- 11993483
TI  - Drug companies maintain "astounding" profits.

PMID- 11993484
TI  - Dying woman loses her battle for assisted suicide.

PMID- 11993485
TI  - One in 12 children dies before age 5 from preventable disease.

PMID- 11993486
TI  - Intravenous immunoglobulin increases risk of thrombotic events.

PMID- 11993487
TI  - India's health levels a mix of success and embarrassment, says report.

PMID- 11993488
TI  - Nigeria recommends jail terms to eradicate female genital mutilation.

PMID- 11993490
TI  - Germany finally revamps its medical training.

PMID- 11993491
TI  - Canada considers maximum waiting times for patients.

PMID- 11993492
TI  - Surgeons postpone work as insurer goes broke.

PMID- 11993493
TI  - Psychiatric effects of terrorist attacks are underestimated.

PMID- 11993494
TI  - Commentary: Exogenous glucocorticoids influence adrenal function, but assessment
      can be difficult.

PMID- 11993495
TI  - Mortality and volume of cases in paediatric cardiac surgery. Volunteered
      mortality data may be unreliable.

PMID- 11993496
TI  - A case of murder and the BMJ. Was it truly murder or sudden infant death
      syndrome?

PMID- 11993497
TI  - Depression and unintended pregnancy in young women. Unmarried women do not show
      psychological harm from abortion.

PMID- 11993498
TI  - Depression and unintended pregnancy in young women. Women's marital status may
      not have been accurate in study.

PMID- 11993499
TI  - Depression and unintended pregnancy in young women. Readers should bear in mind
      potential conflict of interest.

PMID- 11993500
TI  - Hound of the Baskervilles effect. Bad4U?

PMID- 11993501
TI  - Bare-bones health plans: are they worth the money?

PMID- 11993502
TI  - Assessing the threat of bioterrorism: are we ready?

PMID- 11993503
TI  - In pursuit of long-term care: ensuring access, coverage, quality.

PMID- 11993504
TI  - A Medicare prescription drug benefit: focusing on coverage and cost.

PMID- 11993505
TI  - Improving health care quality: can federal efforts lead the way?

PMID- 11993506
TI  - Versatile roles for sonic hedgehog in gut development.
AB  - Sonic hedgehog (Shh) is a gene encoding a protein that can be secreted and act as
      a morphogen. The protein exerts versatile and important effects on the
      surrounding cells by binding a specific receptor, named patched. So far Shh has
      been shown to be involved in the morphogenesis and cytodifferentiation of many
      organ systems, such as notochord, floor plate, limb, pancreas, and pituitary
      gland, to mention only a few examples. Shh is also involved in the determination
      of left-right asymmetry, at least in the chicken embryo. Here we present evidence
      that Shh is one of the key genes whose activity is pivotal for the normal
      morphogenesis and differentiation of digestive organs. Epithelial Shh regulates
      the formation of stomach glands and stratification of the mesenchyme into
      connective tissue and smooth muscle. It exerts its effect often through the
      induction of bone morphogenetic protein (BMP) genes in the mesenchyme. Thus, Shh
      is a key player in the epithelial-mesenchymal interactions in the development of
      the gut.

PMID- 11993507
TI  - Helicobacter pylori infection and hiatal hernia do not affect acid reflux and
      esophageal motility in patients with gastro-esophageal reflux.
AB  - BACKGROUND: The association of H. pylori and hiatal hernia in patients with
      gastroesophageal reflux disease, in terms of acidity and esophageal motility, is
      not well defined. The purpose of this work was to assess whether, in patients
      with gastroesophageal reflux, the presence of H. pylori and hiatal hernia affects
      the severity of esophagitis. METHODS: Reflux symptoms, endoscopy, H. pylori,
      esophageal manometry, and 24-h pH monitoring were evaluated in 37 patients with
      esophageal reflux and 14 healthy volunteers. RESULTS: A total of 75.6% of
      patients with esophageal reflux was positive for H. pylori; 81% had hiatal
      hernia, and only 43.2% showed an acid score by 24-h pHmetry. Esophageal reflux
      patients with H. pylori, hiatal hernia, and an acid score demonstrated higher
      acid parameters compared with those in healthy volunteers. Patients with an acid
      score who were negative for H. pylori tended toward more acid reflux events than
      patients with an acid score who were positive for H. pylori, a difference that
      did not reach significance. The same situation existed with patients with an acid
      score and hiatal hernia who were negative for H. pylori, but the tendency did not
      achieve significance. Independent analysis of patients with Savary-Miller stage
      II and III esophagitis showed results that were not different from the combined
      analysis of stage II and III patients. Amplitude and contraction-duration
      parameters of the esophageal wave, and the number of high-pressure and prolonged
      contractions were not different among the reflux groups. Wave amplitude in the
      lower third of the esophagus was significantly lower in esophagitis stage III
      patients with hiatal hernia and in esophagitis stage II and III patients,
      combined, with H. pylori, compared with findings in the healthy volunteers.
      CONCLUSIONS: These results suggest that H. pylori and hiatal hernia in patients
      with esophageal reflux do not constitute risk factors that affect the severity of
      esophagitis.

PMID- 11993508
TI  - Helicobacter pylori prevalence in dentists in Japan: a seroepidemiological study.
AB  - BACKGROUND: The infection mode of Helicobacter pylori is not well known. In order
      to prove that frequent exposure to saliva and dental plaque does not constitute a
      risk for acquiring H. pylori infection, we tested the hypothesis that the
      prevalence of H. pylori in dentists in Japan is the same as that in controls. We
      also studied factors associated with H. pylori prevalence by multivariate
      analysis. METHODS: We examined serum anti-H. pylori-IgG in 232 Japanese subjects
      (116 dentists and 116 age- and sex-matched nonclinical controls). Participants
      were given a questionnaire that included demographic data, life style, past
      history, and gastrointestinal symptoms, and dental practice. RESULTS: We analyzed
      the results for 111 dentists and 111 controls after exclusion of those who had an
      equivocal titer. The seroprevalence of H. pylori was 42.3% in dentists and 40.0%
      in controls. With multiple logistic regression, age was selected as the only
      independent variable correlated with seroprevalence (P = 0.0002; coefficient of
      determination 0.11). Factors associated with dental practice were not
      significant. CONCLUSIONS: We conclude that dental practice in Japan does not
      increase the risk of H. pylori infection for dentists.

PMID- 11993509
TI  - Basic studies on a labeled anti-mucin antibody detectable by infrared
      fluorescence endoscopy.
AB  - BACKGROUND: We developed a fluorescent dye, indocyanine green (ICG)-sulfo-OSu,
      which was excited by infrared rays and conjugated to various antibodies. We
      attempted to clarify the staining patterns of antisulfomucin and anti-MUC1
      antibodies in gastrointestinal cancer. We then evaluated the potential of the dye
      as a fluorescent label for antibodies specific to cancer, to be used as a
      diagnostic method for microcancer, with infrared fluorescence endoscopy. METHODS:
      Paraffin sections of samples collected from 10 patients with esophageal cancer,
      30 patients with gastric cancer, and 20 patients with colorectal cancer were
      immunohistologically stained using an anti-sulfomucin antibody and an anti-MUC1
      antibody, and the staining patterns were examined. If a section had a high
      staining intensity, it was reacted with the ICG-suflo-OSu-labeled antibody and
      evaluated with infrared fluorescence imaging. RESULTS: The staining patterns with
      the antibodies varied depending on the organs and the histological types and
      depth of the cancers, but the staining was generally good and the staining on the
      mucosal surface of cancer tissues was retained. Good images of cancer cells could
      be obtained by infrared fluorescence observation using the ICG-sulfo-OSu-labeled
      anti-MUC1 antibody. CONCLUSIONS: The anti-MUC1 antibody stained gastrointestinal
      cancer cells well, and nearly specific infrared fluorescence in cancer tissues
      was observed using the labeled anti-MUC1 antibody. The ICG-sulfo-OSu-labeled anti
      MUC1 antibody has possible usefulness for the screening of cancer via infrared
      fluorescence endoscopy.

PMID- 11993510
TI  - The beneficial effect of azathioprine on maintenance of remission in severe
      ulcerative colitis.
AB  - BACKGROUND: The search is on to find more effective drug regimens for patients
      with severe ulcerative colitis, as conventional drugs such as sulfasalazine and
      its congeners fail to prevent relapse in a significant number of patients.
      Azathioprine has also been reported to be useful as a steroid-sparing drug in
      patients who suffer from frequent relapses. As these drugs when used individually
      fail to sustain remission in a significant number of patients, we evaluated the
      combination of these two drugs. METHODS: Thirty-five newly diagnosed patients
      with severe ulcerative colitis were randomized into two groups; group A
      (combination therapy) received sulfasalazine and azathioprine, while group B
      (sulfasalazine monotherapy) received sulfasalazine and placebo. In addition, all
      the patients received steroids initially to achieve clinical remission. The
      patients were followed-up for a period of 1 year. The therapeutic outcome was
      measured by the number of patients who suffered relapse in each group. RESULTS:
      All the patients completed the 1-year study period. While 4 patients (23.5%) in
      group A suffered relapse of disease, 10 (55.6%) in group B suffered relapse, the
      difference being statistically significant. The relapse-free period was also
      significantly longer in group A. CONCLUSIONS: Combination therapy (sulfasalazine
      and azathioprine) is more effective than sulfasalazine and placebo in the
      maintenance of remission in patients with severe ulcerative colitis.

PMID- 11993511
TI  - Experimental and bioinformatics comparison of gene expression between T cells
      from TIL of liver cancer and T cells from UniGene.
AB  - BACKGROUND: The major difficulty of mapping parallel gene expression obtained
      from solid tumors is mainly due to contaminating cells. In this study, by
      applying a strategy of parallel gene expression at a cell-cluster or colony
      level, we have identified the gene expression pattern of T cells within tumor
      infiltrating lymphocytes (TJLs) obtained from two liver cancer patients. METHODS:
      Here a new method was utilized to analyze the parallel gene expression. By using
      bioinformatics analysis, the data were also compared with T-cell gene expression
      present in UniGene. RESULTS: Our results demonstrated that 18 genes in specimen A
      and 13 genes in specimen B were highly expressed after the removal of a
      nonspecific TIL cDNA library, by pairing gene hybridization; the genes were
      expressed in CD3+ cells from peripheral blood mononuclear cells (PBMC). By using
      BlastN search, 17 of the 18, and 12 of the 13 sequences were exhibited,
      respectively, in Homo sapiens, with a range of BlastN E values of 0 to 4 x 10(
      13). The LocusLink distribution in chromosomes obtained from both specimens was
      not significantly different; 17 of 19 putative genes (both specimen A and
      specimen B) were observed in the UniGene cluster in Homo sapiens, except for
      dihydropyrimidinase-related protein-3 and diacyglycerol kinase alpha.
      Interestingly, only 4 of 19 (21%) putative genes were displayed in the T-cell
      UniGene database (i.e., LD-78 in Hs. 73817, IL-8 in Hs. 624, TRAIL in Hs. 83429,
      and Fas ligand in Hs. 2007). CONCLUSIONS: By comparison with the reported data
      and UniGene, the parallel gene expression of T cells obtained from TIL can
      provide essential new insights into T-cell activity, T-cell extravasation into
      tumor tissues, and T-cell cytotoxicity against tumor cells.

PMID- 11993512
TI  - Hepatitis B genotypes and precore/basal core promoter mutants in HBeAg-negative
      chronic hepatitis B.
AB  - BACKGROUND: Mutations in the precore stop codon (G1896A) and the basal core
      promoter (A1762T and G1764A) are frequently found in hepatitis B envelope antigen
      (HBeAg)-negative chronic hepatitis B. However, the clinical significance of these
      mutations remains controversial. We therefore investigated the influence of
      hepatitis B virus (HBV) genotypes, as well as precore/basal core promoter
      mutants, on the clinical and virological features of patients with HBeAg-negative
      chronic hepatitis B. METHODS: Serum samples from 37 patients with HBeAg-negative
      chronic hepatitis B were collected for serological and molecular assays. The
      precore and basal core promoter regions were amplified by polymerase chain
      reaction and the amplicons were directly sequenced and analyzed. HBV genotype was
      determined by polymerase chain reaction-restriction fragment length polymorphism.
      RESULTS: Most of the patients had detectable serum HBV DNA, and genotypes B and C
      were the predominant strains. The overall prevalence of the precore stop codon
      mutant and basal core promoter mutant was 67% and 60%, respectively. The baseline
      clinical and virological features of patients with genotype B and genotype C
      infection were comparable. However, in the patients with precore/basal core
      promoter dual mutations there was a significantly lower proportion of individuals
      with a high detectable serum HBV DNA level (>100pg/ml) than in the patients with
      either the precore stop codon mutation alone or the basal core promoter mutation
      alone (P = 0.04 by the logistic regression test for the trend). CONCLUSIONS: Our
      data suggest a high prevalence of precore stop codon and basal core promoter
      mutation in Taiwanese patients with HBeAg-negative chronic hepatitis B, and the
      influence of the basal core promoter mutation on HBV replication is modulated by
      the emergence of the precore stop codon mutation.

PMID- 11993513
TI  - Regression of MALT lymphomas coexisting in the duodenal bulb and the stomach by
      eradication of Helicobacter pylori.
AB  - We report the regression of coexisting mucosa-associated lymphoid tissue (MALT)
      lymphomas in the duodenal bulb and gastric corpus brought about by Helicobacter
      pylori eradication. During an endoscopic examination, multiple polyps in the
      duodenal bulb were observed in a 62-year-old woman. The pathology of the duodenal
      polyps was low-grade B-cell MALT lymphoma. Gastric MALT lymphoma was also
      detected in biopsies of rough mucosa from the gastric corpus. Southern blot
      analysis showed rearranged bands of DNA immunoglobulin heavy chain J portion (IgH
      J) in both lesions, but the positions of these bands were different in the two
      lesions. H. pylori was recognized in the gastric mucosa by positive serum H.
      pylori antibody and urease tests, while bacterial bodies were not found in the
      duodenal bulb. With 1 year after the successful eradication of H. pylori, both
      the lesions, that in the duodenal bulb and that in the gastric corpus, had
      disappeared. Furthermore, positive rearrangement of IgH-J was not found at either
      of the lesion sites. In May 2000, 3 years after the treatment, endoscopic
      surveillance failed to find any recurrence of these malignant lymphomas.

PMID- 11993514
TI  - Carcinoma of duodenum arising from Brunner's gland.
AB  - Primary carcinoma of the duodenum is a rare lesion. In conjunction with the
      widespread use of panendoscopy, reported cases of carcinoma of the duodenum have
      recently increased. Although benign hyperplasia of Brunner's gland is well
      documented, duodenal carcinoma originating in Brunner's gland is extremely rare,
      and, consequently, there is little data on the morphological or histochemical
      characteristics. We report here a case of early duodenal carcinoma arising from
      Brunner's gland, whose origin was proven by mucin immunohistochemistry.

PMID- 11993515
TI  - Ulcerative colitis associated with Takayasu's disease in two patients who
      received proctocolectomy.
AB  - Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in
      Japan. Here, we report two patients with both diseases who received a total
      proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC,
      was first diagnosed with TD at the age of 10 years. Subsequently, she was
      diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and
      DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary
      artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal
      coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy.
      Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13
      years. Severe symptoms, indicating fulminant UC, started 1 month prior to
      hospitalization. She was judged as needing surgery because the symptoms were not
      alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19),
      B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing
      of the right renal artery; however, her renal function was normal. Based on these
      findings, we performed a three-stage operation for total proctocolectomy.
      Previously, we have reported that the DRB1*1502 and DRw11 genes were closely
      related to the intractability of UC. To date, we have not determined whether or
      how the DRB1*1502 gene might be related to TD. As the number of cases of UC
      associated with TD increases, it will be necessary to examine their DR2 subtypes.

PMID- 11993516
TI  - Aggressive angiomyxoma of the perineum originating from the rectal wall.
AB  - Aggressive angiomyxoma (AA) is a rare mesenchymal tumor that preferentially
      involves the pelvic and perineal regions, and is characterized by frequent local
      recurrences. We describe here a case of large AA in a 31-year-old woman. The
      patient was admitted to our hospital with a mass in the perineal region,
      associated with severe menstrual pain. Although her past medical history was
      unremarkable, she had spotty pigmentation on the lips. Magnetic resonance imaging
      showed a large mass in the abdominal pelvis traversing the pelvic diaphragm just
      to the right of the anus, and the border between the tumor and the rectal wall
      was indistinct. Pathology examination of a frozen intraoperative specimen
      suggested AA, and, therefore, we completely resected the tumor, using a combined
      abdominoperineal approach. The tumor was attached to the right wall of the rectum
      and the pelvic diaphragm between the anus and the puborectalis. The patient
      recovered uneventfully and there has not been any evidence of local recurrence
      for 3 years postoperatively. We consider that abdominoperineal resection may be
      an appropriate treatment for a large AA infiltrating to the perirectal tissues,
      because the high recurrence rate of this disease has been attributed to
      incomplete surgical excision.

PMID- 11993517
TI  - Ulcerative colitis complicating pseudomembranous colitis of the right colon.
AB  - A 65-year-old man in the remission stage of ulcerative colitis developed severe
      bloody diarrhea and high fever. He was treated with imipenem/cilastatin and
      clindamycin for infectious enterocolitis at a local hospital, but there was no
      improvement in his condition. Steroid pulse therapy was also ineffective.
      Colonoscopy revealed pseudomembranous colitis extending from the ascending colon
      to the cecum, and Clostridium difficile toxin was positive in the feces. The
      administration of vancomycin in addition to oral steroids resulted in rapid
      improvement of the condition. Total colonoscopy is recommended for precise
      diagnosis when patients with ulcerative colitis develop intractable diarrhea
      during or after antibiotic therapy.

PMID- 11993518
TI  - Fatal colorectal cancer in juvenile polyposis syndrome.

PMID- 11993519
TI  - Do immunosuppressants really work as maintenance therapy after the achievement of
      remission of severe ulcerative colitis?

PMID- 11993520
TI  - Hepatitis B virus: mutations in the precore/basal core promoter and viral
      replication.

PMID- 11993521
TI  - Chronic inflammatory demyelinative polyneuropathy.

PMID- 11993522
TI  - Symptomatic carotid artery stenosis.

PMID- 11993523
TI  - A prospective study of the incidence, prevalence and mortality of multiple
      sclerosis in Leeds.
AB  - OBJECTIVE: To establish the prospective incidence of multiple sclerosis and
      mortality rates of people with multiple sclerosis in Leeds Health Authority and
      an updated prevalence of multiple sclerosis on 31 October 1999. METHODS: A
      population based prevalence register established on 30 April 1996 was maintained
      by prospectively registering all new cases of multiple sclerosis, flagging all
      cases with the National Health Service Central Register for notification of
      deaths and by registering all new clinical events. General practitioners notified
      patients with multiple sclerosis moving into or out of the area. RESULTS: 136
      incident cases were prospectively registered from 30 April 1996 living in Leeds
      Health Authority (with an estimated resident population of 728,840). 57 deaths
      were notified. 792 people with multiple sclerosis were identified living in Leeds
      on 31 October 1999. The mean annual incidence rate for the three-year period 1996
      1998 was 6.1/10(5) (95% CI: 5.1-7.2). The sex ratio of incident cases was 2.3 to
      1 women to men. On 31 October 1999 the prevalence of multiple sclerosis in the
      Leeds Health Authority was 108.7/10(5) (95% CI: 101.2-116.5). This compares with
      a prevalence of 97.3/10(5) (95% CI: 90.3-104.7) on 30 April 1996. The prevalence
      of definite and probable multiple sclerosis was 93.3/10(5) (95% CI: 86.4-100.6)
      and of suspected multiple sclerosis was 15.4/10(5) (95% CI 12.7-18.5). Crude
      annual mortality rates of people with multiple sclerosis for 1997 and 1998 were
      1.9/10(5) (95% CI: 1.1 to 3.2) and 3.2/10(5) (95% CI: 2.0 to 4.7). Multiple
      sclerosis was noted as the underlying cause of death in 8 (14%) cases.
      CONCLUSION: The incidence of multiple sclerosis in the Leeds Health Authority is
      similar to that in the south of the United Kingdom. The difference in successive
      prevalence figures is less than that published in other serial studies. Multiple
      sclerosis was notified as the underlying cause of death in a minority of deaths
      in people with multiple sclerosis.

PMID- 11993524
TI  - Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar
      ischaemic stroke: innocent bystanders?
AB  - OBJECTIVES: Lacunar infarcts are thought to be mostly due to intracranial small
      vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct
      does have severe ipsilateral internal carotid artery (ICA) or middle cerebral
      artery (MCA) disease, it is unclear whether the arterial disease is causative or
      coincidental. If causative, we would expect ICA/MCA disease to be more severe on
      the symptomatic side than on the asymptomatic side. Therefore, our aim was to
      compare the severity of ipsilateral with contralateral ICA and MCA disease in
      patients with lacunar ischaemic stroke. METHODS: We studied 259 inpatients and
      outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We
      used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to
      identify ICA and MCA disease, and compared our results with previously published
      data. RESULTS: In our study, there was no difference between the severity of
      ipsilateral and contralateral ICA stenosis within individuals (median difference
      0%, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and
      contralateral stenosis). The overall prevalence of severe ipsilateral stenosis
      was 5%, and the prevalence of severe contralateral stenosis was 4% (OR 1.6, 95%
      CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and
      contralateral MCA disease. A systematic review of the other available studies
      strengthened this conclusion. CONCLUSION: Carotid stenosis in patients with a
      lacunar ischaemic stroke may be coincidental. Further studies are required to
      elucidate the causes of lacunar stroke, and to evaluate the role of carotid
      endarterectomy.

PMID- 11993525
TI  - Conservative treatment options for carpal tunnel syndrome: a systematic review of
      randomised controlled trials.
AB  - Carpal tunnel syndrome (CTS) is a common disorder, for which various conservative
      treatment options are available. The objective of this study is to determine the
      efficacy of the various conservative treatment options for relieving the symptoms
      of CTS. Computer-aided searches of MEDLINE (1/1966 to 3/2000), EMBASE (1/1988 to
      2/2000) and the Cochrane Controlled Trials Register (2000, issue 1) were
      conducted, together with reference checking. Included were randomised controlled
      trials evaluating the efficacy of conservative treatment options in a study
      population of CTS patients, with a full report published in English, German,
      French or Dutch. Two reviewers independently selected the studies. Fourteen
      randomised controlled trials were included in the review. Assessment of
      methodological quality and data-extraction was independently performed by two
      reviewers. A rating system, based on the number of studies and their
      methodological quality and findings, was used to determine the strength of the
      available evidence for the efficacy of the treatment. Diuretics, pyridoxine, non
      steroidal anti-inflammatory drugs, yoga and laser-acupuncture seem to be
      ineffective in providing short-term symptom relief (varying levels of evidence)
      and steroid injections seem to be effective (limited evidence). There is
      conflicting evidence for the efficacy of ultrasound and oral steroids. For
      providing long-term relief from symptoms there is limited evidence that
      ultrasound is effective, and that splinting is less effective than surgery. In
      conclusion, there is still little known about the efficacy of most conservative
      treatment options for CTS. To establish stronger evidence more high quality
      trials are needed.

PMID- 11993526
TI  - Epidemiology of primary intracranial tumours in NW Italy, a population based
      study: stable incidence in the last two decades.
AB  - Data about the epidemiology of primary intracranial tumours (PIT) are still
      heterogeneous depending on different methodological approach in collecting data.
      In Valle d' Aosta, north west side of Italy, we have carried out a prospective
      consecutive population based study to calculate the incidence of PIT in the last
      decade (1992-1999) and to compare these rates with the previous period (1986
      1991), data reported in a previous paper. The mean annual PIT incidence rate (ri)
      per 100,000 inhabitants was 25.48. The mean annual incidence rates in the two
      period of comparison were adjusted to the 1991 Italian population by the direct
      method. The standardised ratio was 26.43 in the previous period and 23.24 in the
      second decade. There is no statistically significant difference. The mean annual
      PIT incidence rates by tumour types were meningiomas 13.27/100,000 (men 9.77;
      women 16.7), neuroepithelial group 9.3 (men 10.62; women 8.1), adenomas 1.26,
      neurinomas 0.7. Mean annual incidence rates by tumour class were also stable. The
      stable incidence rate in the two periods and the similar incidence in England
      (21.04/100,000 person year), strengthen the evidence for a stable incidence rate
      of PIT in the last decade. These three papers used similar methodology. The
      homogeneous methodology allows comparison and further evaluation.

PMID- 11993527
TI  - Quantification of circulating anti-Hu antibody in serial samples from patients
      with paraneoplastic neurological syndromes: possible correlation of antibody
      concentration and course of neurological symptoms.
AB  - Serial samples, spanning an observation period of 4 to 10 years, from five
      patients with anti-Hu associated paraneoplastic neurological syndromes (PNS) were
      investigated with an enzyme linked immunosorbent assay (ELISA) employing
      recombinant HuD protein as antigen. In one patient the anti-Hu antibody
      concentration converted from negative to highly positive levels after the onset
      of neurological symptoms. These findings argue in favour of the idea that an
      autoimmune process, which is generated at the beginning of the neurological
      disease, causes the anti-Hu associated PNS. Serum samples obtained shortly after
      the beginning of the PNS were available from two other patients. The anti-Hu
      antibody levels in these latter patients increased from modest to highly positive
      anti-Hu antibody in follow up samples. In two patients a clear decrease of the
      anti-HuD antibody concentration together with an improvement of paraneoplastic
      neurological symptoms after successful tumour treatment were seen. Overall these
      data suggest that there might be a correlation between the anti-HuD antibody
      level and the clinical course of paraneoplastic neurological symptoms which
      supports further the hypothesis that an autoimmune process is responsible for the
      anti-Hu associated paraneoplastic neurological symptoms.

PMID- 11993528
TI  - Homozygous exon 7 deletion of the SMN centromeric gene (SMN2): a potential
      susceptibility factor for adult-onset lower motor neuron disease.
AB  - Mutations in the telomeric copy of the SMN gene (SMN1) are responsible for almost
      all infantile motor neuron disease (MND). In contrast, the role of the
      centromeric copy of the SMN gene (SMN2) in MND remains unclear. We searched for
      deletions of SMN1 and SMN2 in a group of 11 patients with sporadic adult-onset
      lower motor neuron disease (also referred to as "progressive muscular atrophy")
      and found an excess of patients carrying homozygous deletions of SMN2 exon 7 (36%
      versus 5% in the normal population). This result suggests that SMN2 deletions
      could act as a susceptibility factor for sporadic lower motor neuron disease in
      adults.

PMID- 11993529
TI  - Cognition and health-related quality of life in a well-defined subgroup of
      patients with partial epilepsy.
AB  - To investigate the extent and nature of the objective and subjective cognitive
      deficits and health-related quality of life (HRQOL) in adult outpatients with
      relatively well-controlled partial epilepsy without symptomatic aetiology, who
      were on carbamazepine (CBZ) monotherapy. Furthermore, we studied the influence of
      the epilepsy history and medication on various cognitive functions and the HRQOL.
      56 outpatients (29 male, 27 female, mean age 41.3 years) with partial epilepsy
      were compared with 56 age-, gender-, and education-matched healthy controls.
      Patients were tested on attention, memory, speed of information processing, and
      executive functioning. Questionnaires aimed at measuring self-perceived cognitive
      functioning (CFQ) and HRQOL (SF-36) were administered. Mann Whitney-U tests were
      used to compare the two groups. Linear regression analysis was performed to
      identify the epilepsy and medication-related factors that are associated with
      cognitive functioning and HRQOL. Patients scored lower on measures of attention
      (P = 0.03), learning (P = 0.02) and speed of information processing (P = 0.00).
      Mental aspects of HRQOL such as fatigue were lower (P = 0.00), whereas physical
      functioning was unaffected. These patients also expressed reductions in mental
      functioning as indicated by a low self-perceived cognitive functioning (P =
      0.01). Age at onset, duration of epilepsy, seizure type, seizure frequency,
      localisation, years on CBZ, and CBZ dosage were not related to cognitive
      functioning or HRQOL. Patients with partial epilepsy, even when able to maintain
      regular jobs, have impaired cognition and HRQOL that cannot be attributed to
      their epilepsy history or CBZ dosage or years of CBZ intake. Therefore,
      physicians should be more aware of their cognition and HRQOL, in addition to the
      antiepileptic drug regime.

PMID- 11993530
TI  - Botulinum toxin treatment in atypical parkinsonian disorders associated with
      disabling focal dystonia.
AB  - We investigated the efficacy of botulinum toxin A (BtxA) therapy in patients with
      atypical parkinsonian disorders (APD) exhibiting different types of disabling
      focal dystonia unresponsive to oral drug therapy. Eight patients with
      functionally disabling focal dystonia out of a series of 60 consecutive patients
      with APDs regularly treated at our outpatient movement disorders clinic were
      included. Patients were diagnosed according to established criteria and had
      disabling limb dystonia (n=4) or craniocervical dystonia (n=4) unresponsive to
      oral pharmacological treatment. Localization and dose of BtxA injections was
      determined individually based on clinical examination as well as EMG in patients
      with limb dystonia. BtxA reduced dystonic symptoms in all patients; only one
      developed a transient local side-effect. BtxA was particularly effective in the
      long-term treatment (up to 50 months) of blepharospasm associated with
      progressive supranuclear palsy (PSP). BtxA also alleviated PSP-associated
      retrocollis and orofacial dystonia with lower lip retraction associated with PSP
      and multiple system atrophy. BtxA treatment of limb dystonia in corticobasal
      degeneration (CBD) temporarily improved hand and arm function in early-disease
      stages while treatment in advanced stages reduced pain, facilitated hygiene and
      prevented secondary contractures. Limb dystonia was also alleviated by BtxA
      therapy in one patient with neuronal multisystem degeneration of undetermined
      cause. The results suggest that BtxA therapy may represent an effective means of
      alleviating disabling focal dystonia in different APDs. Particularly in early
      stage APD with disabling limb dystonia local BtxA injections may result in
      functional improvement.

PMID- 11993531
TI  - Retrospective study of a large population of patients with asymptomatic or
      minimally symptomatic raised serum creatine kinase levels.
AB  - A retrospective evaluation of asymptomatic subjects with persistent elevation of
      serum creatine kinase (CK) levels (hyperCKemia) was made in order to verify the
      presence of subclinical myopathy or idiopathic hyperCKemia and to define the most
      appropriate diagnostic pathway. Persistently increased serum CK levels are
      occasionally encountered in healthy individuals. In 1980 Rowland coined for them
      the term idiopathic hyperCKemia. Despite the increase of scientific knowledge,
      several healthy subjects with hyperCKemia still represent a problem for the
      clinician. We made a retrospective evaluation of 114 asymptomatic or minimally
      symptomatic individuals with incidentally detected persistent hyperCKemia. They
      underwent neurological examination and laboratory/instrumental evaluation.
      Skeletal muscle biopsy was performed and thoroughly investigated. Biochemical and
      genetic investigations were added in selected cases. Logistic regression analysis
      was applied. We diagnosed a neuromuscular disorder in 21 patients (18.4%), and
      found, by muscle biopsy and/or EMG, pathological but not conclusive findings in
      57 subjects (50%). The statistic correlation between elevated serum CK levels and
      the probability of making a diagnosis changed according to the age of the
      patient. CONCLUSIONS: Muscle biopsy is the basic tool for screening asymptomatic
      subjects with hyperCKemia. It allowed us to make a diagnosis of disease in 18.4%
      of patients, and to detect skeletal muscle abnormalities in 38.6% of the
      subjects. Interestingly, 31.6% of individuals had completely normal muscle
      findings. These best fit the "diagnosis" of idiopathic hyperCKemia.

PMID- 11993532
TI  - Diagnostic accuracy of the Preclinical AD Scale (PAS) in cognitively mildly
      impaired subjects.
AB  - The Preclinical AD Scale (PAS) is a newly developed scale for the diagnosis of
      preclinical Alzheimer's disease (AD). The PAS combines six markers of preclinical
      AD, namely age, MMSE score, functional impairment, cognitive test performance,
      medial temporal lobe atrophy, and the apolipoprotein E (APOE) genotype. The aim
      of the study was to investigate whether the PAS can accurately identify subjects
      with preclinical AD who become demented during a 2 or 5 year follow-up from among
      subjects with mild cognitive impairment for other reasons. We also investigated
      whether a step-wise scoring of the PAS could reduce the number of elaborate or
      expensive diagnostic procedures. The PAS was scored retrospectively in two
      independent samples of non-demented subjects with mild cognitive impairment older
      than 55 years (average age 65.6 years), who were selected from a memory clinic
      population. In the first sample, the follow-up was 5 years (5-year follow-up
      sample; n=69). In the second sample, the follow-up was 2 years (2-year follow-up
      sample; n=23). The PAS item medial temporal lobe atrophy was not scored in the 5
      year follow-up sample. A PAS cut-off score of 4/5 could best identify subjects
      with AD-type dementia at follow-up (n=25) in the 5-year follow-up sample with a
      sensitivity of 80% and a positive predictive value of 77%. A PAS cut-off score of
      5/6 could best identify subjects with AD-type dementia at follow-up (n=8) in the
      2-year follow-up sample with a sensitivity of 88% and a positive predictive value
      of 70%. The positive predictive value could be increased to 94% in the 5-year
      follow-up sample and to 80% in the 2-year follow-up sample by using higher cut
      off scores, but this reduced the sensitivity. Step-wise scoring of the PAS had
      the same diagnostic accuracy as the total PAS score and reduced the number of
      cognitive assessments by 22 to 38%, the number of assessments of medial temporal
      lobe atrophy by 57 to 74%, and the number of APOE genotypings by 74%. It is
      concluded that the PAS is a useful scale to identify subjects with preclinical AD
      who will become demented during the next 2 or 5 years. Step-wise scoring of the
      PAS can reduce the number of elaborate or expensive diagnostic procedures
      considerably.

PMID- 11993533
TI  - Acute disseminated encephalomyelitis in adults: a reappraisal of clinical, CSF,
      EEG, and MRI findings.
AB  - OBJECTIVES: To establish an adequate definition of acute disseminated
      encephalomyelitis (ADEM) in adults, based on our clinical observations of a case
      series. METHODS: Over a period of three years 10 adult patients with a para- or
      postinfectious disseminated (diffuse or multifocal) syndrome of the CNS
      fulfilling predefined strict criteria for the diagnosis of ADEM were encountered
      and systematically followed. RESULTS: The age ranged from 21 to 62 years, two
      were men. MRI was normal in 5 patients and only mildly abnormal in the remaining
      patients. CSF was normal in 5 patients and mildly abnormal in the remainder, EEG
      was abnormal in 7/8 patients. All patients survived and were followed over a
      period of 30 months (range: 8 to 48 months). Nine patients were left with some
      residual defects, consisting most often of a mild cognitive impairment.
      CONCLUSIONS: The EEG as an investigation of brain function can be crucial in
      establishing the organic nature of disease. MRI is important to exclude other
      diffuse or multifocal encephalopathies. However, in contrast to previous reports
      in the literature abnormal MRI should not be considered mandatory in adult ADEM.
      Difficulties in the diagnosis of ADEM are discussed and the importance of
      clinical and paraclinical findings for establishing the diagnosis is outlined.

PMID- 11993534
TI  - Disease severity in multifocal motor neuropathy and its association with the
      response to immunoglobulin treatment.
AB  - Disease progression in multifocal motor neuropathy (MMN) was studied by comparing
      severity and duration of disease. We assessed disease severity by determining
      muscle weakness, disability, conduction block (CB), and distal and proximal
      compound muscle action potential (CMAP)-amplitude in 38 patients with MMN in whom
      disease duration ranged from 6 months to 34 years. As indicator for an ongoing
      immune-mediated process, the response to one course of IVIg treatment was
      measured in 34 patients and associated with disease severity. With increasing
      disease duration, weakness and disability became significantly more severe, and
      the distal and proximal CMAP-amplitude decreased significantly. The number of CBs
      was significantly higher in patients with a disease duration longer than 10 years
      than in those affected less than 10 years. Thirty of the 34 patients responded to
      IVIg treatment. Non-responsiveness to IVIg was not associated with any of the
      disease variables. Severe and widespread weakness was significantly associated
      with a response > or = 2 on the MRC-sum-score. Our results provide evidence for a
      slowly progressive disease course of MMN. The good response to IVIg treatment in
      patients with severe and prolonged disease indicates that progression may be the
      result of an ongoing immune-mediated process. These findings imply that early
      treatment may prevent future progression of weakness and disability in patients
      with MMN.

PMID- 11993535
TI  - Selective hypertrophy of the cauda equina nerve roots.
AB  - Two patients are described with a previously unreported hypertrophic
      radiculopathy of the cauda equina with preservation of peripheral nerve function.
      In one removal of an associated bronchial carcinoid tumour led to marked
      improvement in the neurological condition suggesting a paraneoplastic cause. The
      second patient later developed an external ophthalmoplegia but the underlying
      aetiology remains obscure.

PMID- 11993536
TI  - Apraxia of eyelid opening secondary to a dominant hemispheric infarction.

PMID- 11993537
TI  - Proximal superior division oculomotor nerve palsy from metastatic subarachnoid
      infiltration.

PMID- 11993538
TI  - Botulinum toxin for treatment of masseteric hypertrophy.

PMID- 11993539
TI  - A case of Guillain-Barre syndrome associated with cerebellar ataxia and positive
      serum anti-GD1b IgG antibody.

PMID- 11993540
TI  - Cerebellar degeneration and polyglandular autoimmune syndrome with anti-glutamic
      acid decarboxylase antibodies.

PMID- 11993541
TI  - Eugene Devic (1858-1930).

PMID- 11993542
TI  - Genetic continuum controls brain structure and cognition.

PMID- 11993543
TI  - The children of mothers with eating disorders.
AB  - There is good evidence that children of parents with psychological disorders are
      themselves at increased risk of disturbances in their development. Although there
      has been considerable research on a variety of disorders such as depression and
      alcohol, research on the children of parents with eating disorders has been
      relatively recent. This paper aims to review the evidence and covers a number of
      areas, including genetic factors, pregnancy, the perinatal and postpartum period,
      infancy, and the early years of life, focusing on feeding and mealtimes, general
      parenting functions, and growth. This is followed by a consideration of
      psychopathology in the children, parental attitudes to children's weight and
      shape, and adolescence. What is clear is that although there are numerous case
      reports and case series, the number of systematic controlled studies is
      relatively small, and almost nothing has been written about the children of
      fathers with eating disorders. What is evident from the available evidence is
      that children of mothers with eating disorders are at increased risk of
      disturbance, but that the risk depends on a variety of factors, and that
      difficulties in the children are far from invariable. The paper concludes by
      summarizing five broad categories of putative mechanisms, based on the evidence
      to date, by which eating disturbance in parents can influence child development.

PMID- 11993544
TI  - Neighborhood contextual factors and early-starting antisocial pathways.
AB  - This paper examines research investigating the effects of neighborhood context on
      the onset and persistence of early-starting antisocial pathways across middle and
      late childhood. The review begins by presenting theory and research mapping the
      early-starting developmental pathway. Next, sociologically and psychologically
      based investigations linking neighborhood context and early antisocial behavior
      are examined, in order to posit and evaluate the effects of community economic
      disadvantage, exposure to neighborhood violence, and involvement with
      neighborhood-based deviant peer groups on the development of antisocial behavior.
      It is suggested that middle childhood may represent a critical developmental
      period during which children are at heightened risk for neighborhood-based
      effects on antisocial behavior problems. Key methodological issues are addressed,
      and recommendations for future research integrating developmental pathways and
      neighborhood theory and research are advanced.

PMID- 11993546
TI  - Kudoa dianae sp. n. (Myxosporea: Multivalvulida), a new parasite of bullseye
      puffer, Sphoeroides annulatus (Tetraodontiformes: Tetraodontidae).
AB  - A new multivalvulid myxosporean species, Kudoa dianae sp. n., is described from
      bullseye puffer, Sphoeroides annulatus (Jenyns) (Tetraodontiformes:
      Tetraodontidae). Plasmodia develop in extramuscular sites, in the wall of
      oesophagus and less frequently on mesenteries. Mature spores can reach lumen of
      the digestive tract directly by disruption of plasmodial wall or via macrophage
      transport to the oesophageal epithelium. New species is characterised by
      morphology of spores and by the complete sequence of SSU rRNA gene that differs
      from all hitherto known sequences of Kudoa species. Spore morphology (moderate
      sized, simple non-ornate spores, quadrate in apical view) clusters with that of
      Kudoa scienae, K. cerebralis, K. chilkaensis, K. leiostomi, K. finduli, K.
      cascasia and K. ovivora. Analysis of phylogenetic relationships (using SSU rRNA
      gene sequences) among five Kudoa species, the molecular data of which are
      available thus far, revealed that K. dianae is distinguishable from these five
      species and that its closest relation is with K. miniauiriculata.

PMID- 11993545
TI  - Issues in parent-child agreement: the case of structured diagnostic interviews.
AB  - There are three primary purposes of this review. First, the review distinguishes
      among three types of reliability and describes the importance of evaluating the
      reliability of child psychopathology assessment instruments for clinical practice
      and research. Second, parent-child reliability findings from 5 of the more
      carefully studied and frequently used Structured (semi and highly) diagnostic
      interviews (The Schedule for Affective Disorders and Schizophrenia for School-age
      Children, The Child Assessment Scale, The Anxiety Disorders Interview Schedule
      for Children. The Diagnostic Interview for Children and Adolescents, and the
      Diagnostic Interview Schedule for Children) are examined. Finally, this review
      explores factors that have been implicated in terms of their potential effect on
      parent-child agreement. In addition, future directions for research and clinical
      practice within this area are identified and potential resolutions to the
      conundrum of parent-child discordance are discussed.

PMID- 11993547
TI  - Fine structure of erythrocytic stages of a Plasmodium tropiduri-like malaria
      parasite found in the lizard Kentropyx calcarata (Teiidae) from north Brazil.
AB  - The fine structure is described of the merogonic stages and gametocytes of a
      Plasmodium tropiduri Aragao et Neiva, 1909-like parasite infecting the teiid
      lizard Kentropyx calcarata Spix from North Brazil. The trophozoites are bordered
      by two membranes, and with growth a pellicle is formed by the addition of an
      inner, thick double layer and fragmented membrane. The same type of inner
      membrane occurs in the pellicle of the merozoites differentiating from the
      meronts. Merozoites contained a large electron-dense body, sometimes seen to be
      embraced by a tubular mitochondrion with a dense matrix. Micro- and
      macrogametocytes are bounded by a double membrane, closely apposed by the
      detached wall of the parasitophorous vacuole. Both contain osmiophilic bodies.
      The microgametocyte contains an electron-dense aggregate, and the macrogametocyte
      has a large mitochondrion and a complex of tubuli and cisternae. These features
      are compared with those described in other malarial parasites.

PMID- 11993548
TI  - Development and release of a malacosporean (Myxozoa) from Plumatella repens
      (Bryozoa: Phylactolaemata).
AB  - During an experiment to transmit Tetracapsula bryosalmonae Canning, Curry, Feist,
      Longshaw et Okamura, 1999 to a laboratory-cultured bryozoan, Plumatella repens L.
      a previously undescribed malacosporean species was noted. This parasite produced
      sacs of spores in the host that reached 1.2 mm in length. The spores released
      from the sacs appeared similar in size to the two species of Tetracapsula
      previously described although slight differences in form were noted. Release of
      spores from the bryozoans was observed associated with the lophophore of the
      host. The use of experimental bryozoan cultures for the examination of
      malacosporeans is described and discussed.

PMID- 11993549
TI  - Neotropical Monogenoidea. 40. Protorhinoxenus prochilodi gen. n., sp. n.
      (Monogenoidea: Ancyrocephalinae), parasite of prochilodus lineatus
      (Characiformes: Prochilodontidae) from south Brazil.
AB  - The monotypic Protorhinoxenus gen. n. is proposed to accommodate a species with
      the following characteristics: 1) tubular sclerotised vagina, 2) vaginal pore
      dextrolateral, 3) ventral and dorsal anchors with undifferentiated elongate shaft
      and base (representing approximately 2/3 of the length of anchor), and 4)
      superficial and deep roots of ventral and dorsal anchors lacking. Protorhinoxenus
      prochilodi sp. n. is described from the gills of Prochilodus lineatus
      (Valenciennes) of the Represa Capivari-Cachoeira, Municipality of Campina Grande
      do Sul, metropolitan area of Curitiba, Parana. Specimens of other probable new
      species of Protorhinoxenus are reported from Prochilodus lineatus of the Rio
      Paranapanema, Municipality of Salto Grande, Sao Paulo; Hoplias spp. of the Rio
      Dois de Fevereiro, Municipality of Antonina, Parana, and the Rio Piraquara,
      metropolitan area of Curitiba, Parana; Leporinus elongatus Valenciennes of the
      Rio Tibagi, Municipality of Jataizinho, Parana; and Schizodon fasciatum Agassiz
      of the Rio Solimoes, island of Marchantaria, near Manaus, Amazonas.
      Protorhinoxenus appears to be a sister group of Rhinoxenus Kritsky, Boeger et
      Thatcher, 1988 based on the following apparent synapomorphies: 1) ventral and
      dorsal anchors lacking superficial and deep roots, 2) ventral and dorsal anchors
      with elongate shaft, and 3) male copulatory organ with counterclockwise rings.

PMID- 11993550
TI  - Preliminary characterisation and extraction of anterior adhesive secretion in
      monogenean (platyhelminth) parasites.
AB  - Secreted anterior adhesives, used for temporary attachment to epithelial surfaces
      of fishes (skin and gills) by some monogenean (platyhelminth) parasites have been
      partially characterised. Adhesive is composed of protein. Amino acid composition
      has been determined for seven monopisthocotylean monogeneans. Six of these belong
      to the Monocotylidae and one species, Entobdella soleae (van Beneden et Hesse,
      1864) Johnston, 1929, is a member of the Capsalidae. Histochemistry shows that
      the adhesive does not contain polysaccharides, including acid mucins, or lipids.
      The adhesive before secretion and in its secreted form contains no
      dihydroxyphenylalanine (dopa). Secreted adhesive is highly insoluble, but has a
      soft consistency and is mechanically removable from glass surfaces. Generally
      there are high levels of glycine and alanine, low levels of tyrosine and
      methionine, and histidine is often absent. However, amino acid content varies
      between species, the biggest differences evident when the monocotylid monogeneans
      were compared with E. soleae. Monogenean adhesive shows similarity in amino acid
      profile with adhesives from starfish, limpets and barnacles. However, there are
      some differences in individual amino acids in the temporary adhesive secretions
      of, on the one hand, the monogeneans and, on the other hand, the starfish and
      limpets. These differences may reflect the fact that monogeneans, unlike starfish
      and barnacles, attach to living tissue (tissue adhesion). A method of extracting
      unsecreted adhesive was investigated for use in further characterisation studies
      on monogenean glues.

PMID- 11993551
TI  - Redescription of Andrya cuniculi (Blanchard, 1891) (Cestoda: Anoplocephalidae), a
      parasite of Oryctolagus cuniculus (Lagomorpha) in Spain.
AB  - Andrya cuniculi (Blanchard, 1891) (Cestoda: Anoplocephalidae) is redescribed from
      Oryctolagus cuniculus (L.) from Spain. Large ranges of variability in body length
      and width, testes number and position of the cirrus sac were observed. An
      external seminal vesicle covered with small glandular cells is present. The
      pattern of development of the uterus is similar to that of Andrya rhopalocephala
      (Riehm, 1881). The only reliable differential characters to distinguish A.
      cunliculi from A. rhopalocephala are the position of the uterus in gravid
      segments and the position of the testes in mature segments. The uterus of A.
      cuniculi occupies the median field and parts of the lateral fields but is
      restricted to the median field in A. rhopalocephala. Testes are distributed more
      symmetrically lateral to the female organs in A. cuniculi but are mostly
      antiporal in A. rhopalocephala.

PMID- 11993552
TI  - Redescription of Proteocephalus bagri and p. Rhamdiae (Cestoda:
      Proteocephalidae), parasites of Rhamdia quelen (Siluriformes: Pimelodidae) from
      South America, with comments on morphological variation.
AB  - The pimelodid fish Rhamdia quelen (Quoy et Gaimard, 1824) in South America
      harbours two species of proteocephalid cestodes, Proteocephalus bagri Holcman
      Spector et Mane-Garzon, 1988 and P. rhamdiae Holcman-Spector et Mane-Garzon,
      1988. These species are redescribed based on a detailed morphological study,
      supported by multivariate analysis (principal component analysis). Features
      distinguishing these species are: (1) the shape of proglottides, (2) the mean
      number of testes, (3) the topography of vitelline follicles, (4) the thickness of
      internal longitudinal musculature, (5) the mean number of uterine branches, (6)
      the ratio of cirrus pouch length to proglottis width, (7) the shape of ovary in
      mature and gravid proglottides and (8) the genital pore position in mature
      proglottides. The specific status of P. bagri and P. rhamdiae is confirmed and
      neotypes of both species are designated.

PMID- 11993553
TI  - Redescription of the female of Gnathia africana (Crustacea: Isopoda: Gnathiidae)
      from southern Africa.
AB  - A redescription of the female of the temporary fish parasite, Gnathia africana
      Barnard, 1914 is provided from specimens reared from final-stage G. africana
      praniza larvae collected from their intertidal fish hosts along the south coast
      of southern Africa. It differs from other known gnathiid females in the shape of
      the frontal border and the number and basic form of pylopod articles. This
      redescription aims to establish a format for future descriptions and
      redescriptions of gnathiid females.

PMID- 11993554
TI  - Bacterial colonisation in the gut of Phlebotomus duboseqi (Diptera: Psychodidae):
      transtadial passage and the role of female diet.
AB  - Bacteria isolated from the gut of different developmental stages of Philebotomus
      duboseqi Neveu-Lcmaire, 1906 belonged almost all to aerobic or facultatively
      anaerobic gram-negative rods. In females, the highest bacterial counts were
      observed two days after bloodfeeding; seven days after bloodfeeding the bacterial
      counts returned to pre-feeding levels. Most isolates were identified
      phenotypically as Ochrobactrum sp. The distinctiveness and homogeneity of the
      phenotypic and genotypic characteristics of Ochrobactrum isolates indicated that
      they belonged to a single strain (designated AK). This strain was acquired by
      larvae from food and passaged transtadially: it was isolated from the guts of
      fourth-instar larvae shortly before pupation, from pupae as well from newly
      emerged females. Most other bacteria found in females were acquired from the
      sugar solution fed to adults. To determine if the midgut lectin activity may
      serve as antibacterial agent females were membrane-fed on blood with addition of
      inhibitory carbohydrates. No significant differences in bacterial infections were
      found between experimental and control groups and we suppose that the lectin
      activity has no effect on gram-negative bacteria present in sandfly gut.

PMID- 11993556
TI  - Considering the "peer" in peer review.

PMID- 11993555
TI  - Occurrence of a new microsporidium in the skeletal muscle of the flying fish
      Cypselurus pinnatibarbatus japonicus (Exocoetidae) from Yakushima, Japan.
AB  - A new microsporidium was observed in the flying fish Cypselurus pinnatibarbatus
      japonicus (Franz) (Exocoetidae) from Yakushima, Japan. Visual examination
      revealed the microsporidium to form white elongate nodules in the host's trunk
      muscle. Monomorphic spores were ovoid to pyriform in shape, with average
      dimensions of 4.1 x 2.2 microm and possessing a polar tube describing 13-15
      coils. Histological observations showed that each parasite focus of infection was
      encapsulated by a host-produced fibrous membrane. The presence of sporophorous
      vesicles was not clearly determined. Ribosomal DNA sequence analyses showed the
      microsporidium to be discrete from other known fish muscle-infecting species and
      to be most closely related to a clade comprising the Pleistophoridae and Glugea
      spp. The parasite is provisionally placed as Microsporidium cypselurus sp. n.

PMID- 11993557
TI  - Self-resolution of alcohol problems in young adulthood: a process of securing
      solid ground.
AB  - Quantitative research findings suggest that young adults resolve alcohol problems
      without participating in support groups or formal treatment programs. However,
      researchers have failed to fully explain the self-resolution process among this
      age group. Thus, the authors used grounded theory to better explicate why and how
      young adults self-resolve alcohol problems. The findings suggest that self
      resolving alcohol problems in young adulthood involves a temporal process of
      seeking and securing solid ground. This process is precipitated by situations in
      which individuals experience precarious footing and eventually begin to lose
      their balance. These culminating events lead young adults to pursue personal
      visions and find safe footing on solid ground, despite some rugged terrain along
      the way.

PMID- 11993558
TI  - Releasing the pause button: mothering twins during the first year of life.
AB  - The purpose of this grounded theory study was to investigate the basic social
      psychological problem mothers of twins experience during the first year after
      delivery and the process they use to resolve this fundamental problem. Life on
      hold was the basic social psychological problem that mothers of twins experienced
      during the first year of their twins' lives. Releasing the pause button was the
      four-stage process mothers progressed through as they attempted to resume their
      own lives. These four phases were (a) draining power, (b) pausing own life, (c)
      striving to reset, and (d) resuming own life. The most vulnerable period for
      mothers of twins is the first 3 months postpartum. Intensive interventions need
      to be in place to support women during this time.

PMID- 11993559
TI  - Long-term dialysis survivors: a transformational experience.
AB  - In this exploratory/descriptive study, the authors examined processes involved in
      some kidney patients' ability to survive on dialysis. Through long semistructured
      interviews with 18 dialysis survivors, they identified four self-affirmations
      that characterized participants' restructuring of self and four sets of illness
      experiences that required restructuring within the context of their extant
      worlds. The denouement involved the participants' transformation into
      comprehensive, active self-managers of their disease, its treatment, and its
      manifestations. The authors describe the participants' affirmations and
      adaptations leading to transformation. Understanding this process paves the way
      for research into the timing and sequence entailed in transformation and lays the
      groundwork for the development of interventions to guide kidney failure patients
      to the positive outcome of transformation: comprehensive, active self-management.

PMID- 11993560
TI  - Living with loss: middle-aged men face spousal bereavement.
AB  - Spousal bereavement is one of the most profoundly disturbing events encountered
      in the human life span. Research has shown that conjugal bereavement has
      significant physical and psychological consequences for the surviving spouse. In
      American culture, men and women experience bereavement in different ways. The
      author used in-depth interviews in the tradition of phenomenology to collect data
      from 8 men aged 41 to 54 years who had experienced the death of their spouse
      within the previous 8 months to 6 years. The research revealed the lived
      experience of spousal bereavement to be a journey from the realization of
      irreconcilable loss through themes of responding to the loss and living through
      the loss toward reclamation and reconstruction of a life.

PMID- 11993561
TI  - Who should receive subsidized psychotherapy?: Analysis of decision makers' think
      aloud protocols.
AB  - Three groups of judges representing clinical, political, and laypersons'
      perspectives were given the task of prioritizing patients for subsidized
      psychotherapy within the Swedish health care system. The authors documented the
      judges' decision-making processes in think-aloud protocols and analyzed them
      qualitatively, focusing on the conflict between the urgency of a case and its
      suitability for treatment. In an earlier statistical analysis of the same
      material, clinicians had seemed to pay more attention to suitability criteria,
      whereas health care officials and laypersons prioritized based on urgency. The
      qualitative findings confirmed the centrality of this conflict and contributed to
      a deeper understanding of decision makers' ways of coping with it. Their
      conceptions of suitability and urgency were also elucidated by analysis of the
      think-aloud protocols.

PMID- 11993562
TI  - Evolving routines: preventing fatigue associated with lung and colorectal cancer.
AB  - Some individuals with cancer develop fatigue whereas others do not. To begin the
      development of a biobehavioral model that could explain this phenomenon, the
      authors interviewed 29 individuals with lung and colorectal cancer before,
      during, and after treatment and obtained evaluable data for 18. Blood samples and
      body weight were obtained at the time of each interview. A three-stage process,
      evolving routines, and an adaptive behavioral mode labeled gliding characterized
      those who reported little or no fatigue, even when hemoglobin levels were low.
      Three other nonadaptive behavioral modes (inertia, disorganization, and
      overexertion) characterized those who reported fatigue. Individuals with similar
      disease and treatment profiles seldom demonstrated the same behavioral or
      biological response patterns.

PMID- 11993563
TI  - Understanding and practice: a 7-year follow-up study on implementation of a
      cardiac rehabilitation program.
AB  - The authors explore the perspectives of managers, health care professionals, and
      patients on a comprehensive cardiac rehabilitation program. Using qualitative
      methodology, they compare and analyze results from individual interviews and two
      conceptual modeling seminars held 7 years apart. Professionals and managers
      understood their own tasks in a professional-centered way that did not include
      the client's perspective. Patients believed they were not seen in their whole
      context. Initially, health care organization was fragmented, lacking clear
      leadership, coordination, and communication between levels of care. However, lack
      of common understandings of structure, process, and outcome in cardiac
      rehabilitation services hampered the implementation of program changes.

PMID- 11993564
TI  - Reconstructing intimate violence: the structure and content of recollections of
      violent events.
AB  - The purpose of this article is to explore the structure and content of
      recollections of violent events among cohabiting partners. The authors used
      qualitative methodology to examine 48 in-depth interviews. Content analysis of
      the interviews yielded two parallel and interrelated continua: One represented
      the life circumstances (staying in spite of violence) impinging on the
      recollections; the other dealt with the content of the memories of violent
      events. These two interacted according to a series of structural features. Both
      men and women living in violent relationships described a contextual variation
      ranging from choosing to stay to being prevented from leaving. The memory of
      violence was constructed in a manner meant to achieve coherence with the
      appropriate context.

PMID- 11993565
TI  - The benefits of being a nurse in critical social research practice.
AB  - In critical social research, or research that evokes feminist or critical
      epistemological positions, researchers must examine their own situatedness vis-a
      vis their research participants and work toward methods that break down the
      hierarchies inherent in the research relationship and empower research
      participants. Such aspects of research practices necessitate strong interpersonal
      skills, characteristic of many nurses. Drawing on their experiences, the authors
      critically appraise the benefits of nursing in critical social research practice.
      Nurses can move beyond their own discipline to use their skills, identity, and
      intersubjective way of relating with others to gain access to participants and
      data. Through a unique process of building meaning and interpreting data, nurse
      researchers are well placed to take effective actions for change.

PMID- 11993566
TI  - Language and power: ascribing legitimacy to interpretive research.
AB  - More than merely describing what constitutes a good or truthful interpretation,
      all judgments about the legitimacy of knowledge claims can be understood as
      enacting relations of power. That is, our understanding of what it means to make
      a reasonable claim to knowledge is already caught up in relations of power that
      privilege some perspectives and marginalize others. Language, understood as
      productive rather than reflective of meaning, both enables and constrains the
      kinds of statements we are entitled to make. Competing discourses do not exist
      equally in the world but rather differ in terms of what they are held to explain
      and what effect they have. The authors explore these issues and suggest that
      evaluating interpretive research involves not only epistemological issues but
      also questions of value and power.

PMID- 11993567
TI  - A simple method for calculating the financial balance of a hospital, based on
      proportional dividing.
AB  - It is necessary to estimate financial status to determine hospital management
      policy. The costs and revenues (financial balance) of each hospital division are
      one good index. However, it is difficult to calculate the financial balance for
      each division, since clinics and central services are intricately involved with
      each other There are no reports on a pragmatic method for calculating the
      financial balance. We devised a simple method based on proportional dividing.
      Consequently, one individual was able to complete the calculation for our
      hospital, which consists of 1300 beds and 23 clinics, without using the central
      hospital computer system.

PMID- 11993568
TI  - Mobile computing in the humanitarian assistance setting: an introduction and some
      first steps.
AB  - We developed a Palm operating system-based handheld computer system for admin
      istering nutrition questionnaires and used it to gather nutritional information
      among the Burmese refugees in the Mae La refugee camp on the Thai-Burma border
      Our experience demonstrated that such technology can be easily adapted for such
      an austere setting and used to great advantage. Further, the technology showed
      tremendous potential to reduce both time required and errors commonly encountered
      when field staff collect information in the humanitarian setting. We also
      identified several areas needing further development.

PMID- 11993569
TI  - Integration mechanisms and hospital efficiency in integrated health care delivery
      systems.
AB  - This study analyzes integration mechanisms that affect system performances
      measured by indicators of efficiency in integrated delivery systems (IDSs) in the
      United States. The research question is, do integration mechanisms improve IDSs'
      efficiency in hospital care? American Hospital Association's Annual Survey (1998)
      and Dorenfest's Survey on Information Systems in Integrated Healthcare Delivery
      Systems (1998) were used to conduct the study, using IDS as the unit of analysis.
      A covariance structure equation model of the effects of system integration
      mechanisms on IDS performance was formulated and validated by an empirical
      examination of IDSs. The study sample includes 973 hospital-based integrated
      health care delivery systems operating in the United States, carried in the list
      of Dorenfests Survey on Information Systems in Integrated Health care Delivery
      Systems. The measurement indicators of system integration mechanisms are
      categorized into six related domains: informatic integration, case management,
      hybrid physician-hospital integration, forward integration, backward integration,
      and high tech medical services. The multivariate analysis reveals that
      integration mechanisms in system operation are positively correlated and
      positively affect IDSs' efficiency. The six domains of integration mechanisms
      account for 58.9% of the total variance in hospital performance. The service
      differentiation strategy such as having more high tech medical services have much
      stronger influences on efficiency than other integration mechanisms do. The
      beneficial effects of integration mechanisms have been realized in IDS
      performance. High efficiency in hospital care can be achieved by employing proper
      integration strategies in operations.

PMID- 11993570
TI  - Automated production of an on-line laboratory reference manual from a laboratory
      information system.
AB  - Laboratories provide information beyond test results, including information
      related to patient preparation, specimen collection and handling, test
      methodology, test availability, and interpretation of results. Most laboratories
      publish reference manuals to distribute this information to clients, while
      relying on the laboratory information system to provide this information to
      laboratory staff. Maintaining duplicate sources of information is expensive and
      error-prone, and printed materials become rapidly outdated. We developed a
      process to automate the production of a web-based reference manual directly from
      the laboratory information system, using a combination of MUMPS programs and HTML
      templates. We now focus our resources to assure that the laboratory information
      system database is accurate and complete, and then with minimal additional effort
      or expense produce an up-to-date on-line reference manual. We are therefore able
      to provide better sources of information in a sustainable manner.

PMID- 11993571
TI  - Design of microcontroller-based EMG and the analysis of EMG signals.
AB  - In this work, a microcontroller-based EMG designed and tested on 40 patients.
      When the patients are in rest, the fast Fourier transform (FFT) analysis was
      applied to EMG signals recorded from right leg peroneal region. The histograms
      are constructed from the results of the FFT analysis. The analysis results shows
      that the amplitude of fibrillation potential of the muscle fiber of 30 patients
      measured from peroneal region is low and the duration is short. This is the
      reason why the motor nerves degenerated and 10 patients were found to be healthy.

PMID- 11993572
TI  - Theory and applications of biotelemetry.
AB  - In this study, biotelemetry and its evolution is explained in detail. Bioelectric
      and physiological variables could be measured by biotelemetry systems. The
      development of a biotelemetry system and its principal operation are presented.
      The components of a biotelemetry system are explained. Biomedical data has been
      telemetered through every medium between two sites by using a variety of
      modulated energy forms. Designing of the link between transmitter and receiver is
      described. Important factors in designing a backpack or implanted telemeter are
      explained. The main features of implanted biotelemetry units are determined.
      Single-channel and multichannel biotelemetry systems are defined. The types of
      telemetry, and a comparison thereof, are given. The power sources of biotelemetry
      systems and features of different power sources are explained. A survey of
      biotelemetry applications on humans and animals is presented and advantages of
      using biotelemetry systems are determined.

PMID- 11993573
TI  - Data mining to support simulation modeling of patient flow in hospitals.
AB  - Spiraling health care costs in the United States are driving institutions to
      continually address the challenge of optimizing the use of scarce resources. One
      of the first steps towards optimizing resources is to utilize capacity
      effectively. For hospital capacity planning problems such as allocation of
      inpatient beds, computer simulation is often the method of choice. One of the
      more difficult aspects of using simulation models for such studies is the
      creation of a manageable set of patient types to include in the model. The
      objective of this paper is to demonstrate the potential of using data mining
      techniques, specifically clustering techniques such as K-means, to help guide the
      development of patient type definitions for purposes of building computer
      simulation or analytical models of patient flow in hospitals. Using data from a
      hospital in the Midwest this study brings forth several important issues that
      researchers need to address when applying clustering techniques in general and
      specifically to hospital data.

PMID- 11993574
TI  - A study of the medical record interface to natural language processing.
AB  - The information about a patient tends to be handled more on a computer system.
      However, it is not sufficiently rational enough because of the fundamental
      difference between man and a computer. Up to now, man has treated information
      using a natural language. Therefore, if it can be applied to handle medical
      information electrically, that will become more rational. For this reason, we
      developed a new classification method that interfaces a computer with the human
      being, using a natural language. This method was named as a situation-oriented
      medical record, and this depicts changes in a situation by the case frame from a
      viewpoint of man's cognition. Moreover, the medical communication by a natural
      language, which is currently used when a patient changes a hospital, was analyzed
      in order to confirm the validity of this method. In addition, we developed a
      prototype system that allows computers to implement this kind of communication.

PMID- 11993575
TI  - Is the Turkish health care system ready to be a part of the European Union?
AB  - Lately, Turkey is struggling to recover from the economic effects of the economic
      crisis so that the government officials are trying to impose budget cuts in
      health and education sectors. After the United States, the country's national
      defense expenditures are the highest among the NATO countries. Therefore, Turkey
      allocates only 3-4% of the gross domestic product for health care expenses.
      Overall, the health status in Turkey is the lowest among the European Union
      countries; infant mortality rate is about 45 per 1000 live births, which is the
      highest on the European continent, and per capita health care expenditure is
      $120. Although 75% of the people are covered by some type of public insurance,
      25% of the Turkish people do not have any insurance coverage. The national system
      is funded by taxes (43%), out of pocket payments (32%), and social and private
      insurance premiums (25%). This study examines whether Turkey is ready to be a
      part of the European Union in terms of the health sector of its economy and
      health status of its people.

PMID- 11993576
TI  - Research and development of a radioisotope dose calibrator with background alarm
      used in nuclear medical laboratories.
AB  - In this study, research and development of a prototype background alarm levelled
      radioisotope dose calibrator for nuclear medical laboratories was emphasized. The
      aim was to develop a standard performance, economical dose calibrator (self-made)
      from the ion-chamber to the microcomputer. Dose calibrators are used in nuclear
      medical laboratories for treatment and diagnosis purposes. The device is
      developed using an ion chamber filled with 2 atm pressure argon gas, 3N201 dual
      gate mosfet for the extremely high impedance preamplifier, an Intel 8052AH
      microcontroller for the microcomputer, ADC0804 for the A/D conversion, a Phillips
      2 x 16 character display, and other components. Correction factors are used for
      each radioisotope after the activity measurements, that can be updated and kept
      in the Ni-Cd rechargeable battery-powered RAM memory. To provide safety in
      nuclear medical laboratories, background activity values are measured.

PMID- 11993577
TI  - Role of self-efficacy and behaviour change.
AB  - Behaviour change is an important concept in relation to health promotion and
      disease prevention. Self-efficacy has been identified as an important determinant
      of health behaviour, future health behaviour and health behaviour change. In
      order to effectively facilitate behaviour change, it is essential that
      interventions are research based, and emphasize the utility of theory in
      practice. The effective practice of health promotion and disease prevention
      requires a full understanding of the processes of patient behaviour. This article
      presents the role of the nurse in influencing health-related behaviour change.
      Self-efficacy and related but distinct theories that underpin behaviour change
      are discussed. The empirical evidence that supports the link between self
      efficacy and predictions of health behaviours is also examined.

PMID- 11993578
TI  - Just what does the patient want?

PMID- 11993579
TI  - Australian implantable cardiac defibrillator recipients: quality-of-life issues.
AB  - Implantable cardioverter defibrillators (ICDs) have become a well-established
      therapy for people experiencing potentially lethal dysrhythmias. Australian
      recipients' quality of life and adjustment to the device over time, device
      related complications, shock and associated sensations, and potential sequelae
      have not been widely explored. This paper reports a longitudinal prospective
      study of Australian ICD recipients (n = 74) to determine their responses to the
      device, health-related quality of life over time and shock experiences. A
      questionnaire designed for the study and the Medical Outcomes Trust Quality of
      Life Instrument, the SF36, were completed by recipients prior to and at 3 and 12
      months post insertion. Results show that quality of life decreased for general
      health and social function between 3 and 12 months. Nearly half (49%) of the
      recipients received shocks within 12 months and the majority (92%) of these
      experienced sequelae that could make driving hazardous. Half of the population
      (49%) were driving at 3 months and 69% by 12 months, including 67% of those who
      had been shocked. Twenty-seven percent were hospitalized with device-related
      complications. Driving, the shock experience and rehospitalization, the shock
      experience and driving behaviour are significant issues for those with the
      implanted device. While it is a limitation of the study that partners and carers
      were not included, these findings will also be of interest to them.

PMID- 11993580
TI  - Allowing the patients to sleep: flexible medication times in an acute hospital.
AB  - In 1999, under the leadership and direction of the Director of Clinical Services
      (Nursing), Roger Napthine, Project Consultant, was commissioned to undertake a
      review of medication policies and practices for a regional acute-care hospital.
      This initiative was taken with the view of improving nursing practice and patient
      care. Recommendations from Napthine's review included the trial in a medical and
      a surgical unit of a change in the administration of routine morning and evening
      medication times. A descriptive study that included a convenience sample of 52
      patients and 25 registered nurses was conducted in the two units. The findings
      demonstrated that patients were able to sleep longer. Further, although they
      tended to wake earlier, their 'in hospital' and 'at home' sleeping patterns were
      more closely aligned. There was agreement among the nurse participants that the
      change to flexible medication times allowed patients to sleep longer. However,
      concerns were raised about the impact of the change on other nursing duties,
      particularly those performed in the mornings.

PMID- 11993581
TI  - Early adolescents' HIV-related knowledge, attitudes and behaviour in Finland.
AB  - Finland had a relatively low rate of HIV infection during the first 17 years of
      the epidemic, which began in 1980. Similar to other developed countries around
      the world, information about the infection has been readily available, and this
      helped to reduce the occurrence of HIV contagion, particularly among adolescents,
      a group that is responsible for 50% of HIV infections worldwide. This small-scale
      study investigated HIV-related knowledge, attitudes, and behaviour among a group
      of 171 youths ageed 13-16 years in suburban schools in southern Finland.
      Knowledge levels were relatively low and the disease was somewhat stigmatized,
      but homosexuality was less stigmatized than in other developed countries. The
      results suggest that Finnish adolescents need to be better informed about HIV and
      AIDS. Schools and school nurses could play a crucial role in providing
      information about this incurable disease.

PMID- 11993582
TI  - Critical thinking in nursing education: literature review.
AB  - The need for critical thinking in nursing has been accentuated in response to the
      rapidly changing health-care environment. Nurses must think critically to provide
      effective care while coping with the expansion in role associated with the
      complexities of current health-care systems. This literature review will present
      a history of inquiry into critical thinking and research to support the
      conclusion that critical thinking is necessary not only in the clinical practice
      setting, but also as an integral component of nursing-education programmes to
      promote the development of nurses' critical-thinking abilities. The aims of this
      paper are to: (i) review the literature on critical thinking; (ii) examine the
      dimensions of critical thinking; (iii) investigate the various critical thinking
      strategies for their appropriateness to enhance critical thinking in nurses; and
      (iv) examine issues relating to the evaluation of critical-thinking skills in
      nursing.

PMID- 11993583
TI  - Can the Neuman Systems Model be adapted to the Malaysian nursing context?
AB  - Nursing in Malaysia is still developing as a profession. Issues such as using
      nursing conceptual models or frameworks in the delivery of nursing care have not
      been addressed by the majority of nurses. One reason for this has been the level
      of education and preparation of nurses, while another reason lies with the
      origins of existing nursing conceptual models. Most nursing conceptual models
      have their origins in North America. Their utility by nurses of different
      cultures and academic preparations might not be appropriate. Nursing is a social
      activity, an interaction between the nurse and the patient. It is carried out in
      a social environment within a particular culture. Conceptual models developed in
      one culture might not be readily implanted into another culture. This paper
      discusses how a conceptual model developed in North America; that is, the Neuman
      Systems Model, can be adapted into the Malaysian nursing context.

PMID- 11993584
TI  - Advanced practice in nursing: international perspective.

PMID- 11993585
TI  - Prevalence of fatigue in general practice.
AB  - BACKGROUND: Fatigue is an important symptom in general practice due to its
      association with physical, psychological and social problems. AIM: To determine
      the prevalence of fatigue as an unsolicited symptom during general practice
      consultations. METHODS: A random sample of GPs practising in Ireland was invited
      to provide data on consultations held over one day. Data were recorded on the
      presence of fatigue as a main or supporting symptom, social and demographic
      characteristics. RESULTS: Data were recorded by 89 GPs on 1,428 consultations.
      The prevalence of fatigue was 25%. It was the main reason for attending the
      doctor in 6.5% and a secondary reason in 19%. Sixty-two per cent of patients were
      female and 48% were eligible for free GP services. The mean age was 47.1 years.
      The presence of fatigue was associated with: attending a female GP, being female,
      attending a GP who had been qualified for fewer years and attending the GP
      frequently. CONCLUSION: The prevalence of fatigue reported in this study is over
      three times higher than that reported in earlier work. Doctor characteristics
      appear to be as important as patient characteristics in determining fatigue.

PMID- 11993586
TI  - Hip arthroplasty, changing trends in a national tertiary referral centre.
AB  - BACKGROUND: Despite changes in techniques and management, little has been
      published comparing hip replacement surgery over a three-decade time span. AIMS:
      To document change in the practice of hip arthroplasty in a large elective
      orthopaedic centre. METHODS: A retrospective analysis of 100 patients in 1979 and
      in 1999 comparing demographics, surgical approaches, blood loss, transfusion
      requirements, morbidity and length of stay. RESULTS: In 1999, males predominated,
      spinal anaesthesia had largely superceded general anaesthesia, the anterolateral
      approach had replaced the trans-trochanteric approach, osteoarthritis remained
      the main aetiology and the Charnley prosthesis remained the implant of choice.
      Average blood loss was higher in 1999 compared to 1979 (1,378 vs 1,225 ml) but
      all patients in 1979 were transfused with an average of 2.8 units while in 1999
      one-third of patients were transfused with an average of 1.6 units (p<0.0001).
      Length of stay had fallen from 30.5 days in 1979 to 16.2 days in 1999 (p<0.0001).
      Thromboembolic complications fell from 13% to 2% (p=0.0083). CONCLUSION: The
      incidence of deep venous thrombosis (DVT), pulmonary embolus (PE) and length of
      hospital stay has fallen. Blood loss had changed little but fewer patients
      receive blood transfusion.

PMID- 11993587
TI  - Admissions with chronic obstructive pulmonary disease after publication of
      national guidelines.
AB  - BACKGROUND: The British Thoracic Society (BTS) published guidelines on managing
      acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in 1997.
      AIM: To audit admissions with AECOPD and to see how well these guidelines were
      adhered to. Methods All patients admitted were identified and 50 selected for
      audit. RESULTS: The mean age was 72 years and 52% were female. Admission C
      reactive protein (CRP) and white cell count (WCC) were 49 (12.7) mg/l and 10.97
      (0.64) x 10(9)/l respectively. Six were acidotic and 16 hypercapnoeic. Median
      length of stay (LOS) was six days. Twenty-one fulfilled admission criteria.
      Thirty-seven had > or = 2 Anthonisen criteria. Nine had spirometry performed.
      Correlations were seen between appropriateness of admission score and pH (r=
      0.41, p=0.01) and LOS (r=-0.43, p=0.002) and between Anthonisen criteria score
      and age (r=0.33, p=0.018). Symptom score correlated with PaO2 (r=-0.38, p=0.02),
      LOS (r=0.27, p=0.06) and age (r=0.38, p=0.007). LOS correlated with PaCO2
      (r=0.33, p=0.04). CONCLUSION: Admissions are chiefly comprised of an ill, elderly
      population. Careful adherence to guidelines could result in fewer admissions.

PMID- 11993588
TI  - Feasibility of a men's health promotion programme in Irish primary care.
AB  - BACKGROUND: To assess the feasibility of offering health promotion and preventive
      medicine initiatives in primary care. AIMS: A pilot study aimed at men in general
      practice to establish the uptake, acceptability and effectiveness of
      interventions in health initiatives. METHODS: One thousand men aged 18-65 were
      selected at random from five general practices in the Western Health Board area.
      Practices were randomly allocated to one of four brief interventions:
      cardiovascular screening, cancer screening, stress management or general
      lifestyle advice. RESULTS: Fifty-five per cent of men responded, with 35.7%
      actually attending. There were minor but significant short-term changes in health
      status and behaviours. Participants expressed high levels of satisfaction, but
      tended to prefer interventions with an explicit clinical component. CONCLUSION:
      It is at least as feasible to offer health promotion for men in primary care as
      it is for other demographic groups, but adequate training and resources are
      required.

PMID- 11993589
TI  - The provision of secondary cardiac prevention measures in a hospital cardiac
      clinic population and the relationship to psychological variables.
AB  - BACKGROUND: Implementing preventive measures in patients with established heart
      disease is one of the most effective health promotion activities, but there is
      little research on the relationship between cognition and secondary preventive
      behaviour. AIM: To determine the provision of secondary cardiac prevention
      measures among patients with established heart disease attending a cardiac
      outpatient clinic. METHODS: The study was conducted in an outpatient department
      over a 14-week period in 1999. Management of risk markers was noted from the
      medical records and lifestyle and psychological variables were self-reported.
      RESULTS: Of 294 patients with heart disease, 41% were available for study.
      Fourteen per cent were current smokers, one-quarter of males and one-third of
      females had a body mass index (BMI) greater that 30. Almost 90% attend their GP
      bimonthly, 67% had a normal systolic and 88.3% a normal diastolic pressure, 34%
      had normal cholesterol levels and 75% were on aspirin. Lifestyle variables were
      significantly affected by patient cardiac knowledge, sense of control over their
      heart disease and perceptions of their illness. CONCLUSIONS: These results
      highlight the potential health gain available to patients with established heart
      disease. The results also suggest that psychological factors may play a role in
      patients' health behaviours.

PMID- 11993590
TI  - Tamoxifen as the primary treatment in elderly patients with breast cancer.
AB  - BACKGROUND: With the increasing incidence of breast cancer in patients over 70
      years, there is interest in the best therapeutic approach. AIMS: To review the
      management of breast cancer in elderly women and to identify the factors involved
      in the decision to treat patients with tamoxifen as first line therapy. PATIENTS
      AND METHODS: Between 1986 and 1999, 302 female patients aged > or = 70 years
      presented with primary breast cancer, of whom 219 underwent surgery, 79 received
      tamoxifen as first line treatment and four received primary radiotherapy. A
      retrospective review was performed on these 79 patients and the outcome recorded.
      RESULTS: Of these 79 patients, data was available on 68. Follow-up ranged from
      one to 63 months (median 17 months). Co-morbidity was the principal reason for
      choosing first line tamoxifen therapy in 61% and patient preference in 11%.
      Tumour size was less than 5cm in 51%. In 25% tumour size decreased, in 24% it
      remained stable and in 27% it increased in size following tamoxifen therapy.
      Additional treatment was prescribed for 33% of patients. CONCLUSION: In the
      authors' experience, for those elderly patients suffering considerable co
      morbidity or who refuse surgical intervention, tamoxifen is an acceptable
      alternative.

PMID- 11993591
TI  - Primary torsion dystonia due to the Tor1A GAG deletion in an Irish family.
AB  - BACKGROUND: Early, limb-onset primary torsion dystonia (PTD) is commonly due to a
      trinucleotide GAG deletion in the TOR1A (DYT1) gene on chromosome 9q34. The
      majority of carriers of this mutation conform to a characteristic phenotype that
      is similar in different ethnic populations. AIM: To describe the clinical
      features of affected members of a large Irish family with PTD due to the TOR1A
      deletion. METHODS: Fourteen consenting family members from three generations were
      examined according to a standardised protocol. RESULTS: Five affected individuals
      were identified. Two had a somewhat atypical phenotype with focal and segmental
      upper-limb dystonia without further progression. CONCLUSION: The authors describe
      the clinical features of PTD due to the TOR1A GAG deletion in an Irish family
      illustrating the presence of intrafamilial phenotypic variability.

PMID- 11993592
TI  - Molecular characterisation of human campylobacteriosis in Northern Ireland:
      evidence of clonal stability.
AB  - BACKGROUND: No study has compared Campylobacter isolates from a human source in
      Northern Ireland over an extended period of time. AIM: To investigate the clonal
      stability of thermophilic campylobacters isolated from acute bacterial enteritis
      in Northern Ireland from 1992 to 1999. METHODS: Human isolates (n=272),
      originating from faeces, were characterised at the sub-species level using
      enterobacterial repetitive intergenic consensus sequence (ERIC2)--random
      amplification of polymorphic DNA (RAPD) typing. RESULTS: Thirteen genotypes were
      identified where three types, namely ERIC A, ERIC C and ERIC I, accounted for
      28.3%, 14.3% and 13.6%, respectively. There were no significant associations
      (p>0.05) between sex, age groupings and year of isolation and ERIC2 genotype,
      with the exception of ERIC D, which showed a significant decline in isolation
      with time (p=0.019). CONCLUSIONS: ERIC genotypes were stable over this period,
      except genotype C which was lost during this time. Previous molecular typing
      methods showed campylobacters to be heterogeneous but this study suggests that
      the local human Campylobacter population consists of several common and stable
      genotypes. This study has established a database of local ERIC2 genotypes. This
      methodology may allow the establishment of an all-island database of clinical
      campylobacters that would be valuable in reducing human campylobacteriosis in
      Ireland.

PMID- 11993593
TI  - Thermolabile methylenetetrahydrofolate reductase (C677T): frequency in the Irish
      population.
AB  - BACKGROUND: The genetic variation which underlies the thermolability and low
      enzyme activity of 5,10-methylenetetrahydrofolate reductase (MTHFR; C677T) has
      been extensively studied in many populations, including the Irish population.
      AIM: To describe the examination of the C677T substitution in two new control
      samples drawn from the Irish population. METHODS: A collection of 487 serum
      samples was obtained through the blood transfusion services of both the Republic
      of Ireland and Northern Ireland and a further 115 samples from volunteers.
      RESULTS: In both samples, the frequency of the thermolabile/low enzyme activity
      allele (T) was higher than that previously reported for the Irish population.
      CONCLUSION: This finding thus supports the need for a greater use of internal
      control/family-based association studies, as opposed to the classic case control
      study design, when assessing the contribution of the MTHFR T allele to disease
      processes.

PMID- 11993594
TI  - Airway evaluation on placental support.
AB  - BACKGROUND Prenatal ultrasonography predicting airway obstruction can facilitate
      intrapartum management, revolutionising the approach to potential airway
      difficulties at birth. AIMS: This report presents the first case of this
      procedure attempted in Ireland. RESULT AND CONCLUSION: This case was unsuccessful
      in securing an airway, but the potential for intubation or tracheostomy with an
      intact maternal-foetal circulation provides encouragement for the management of
      future cases.

PMID- 11993595
TI  - Vancomycin-resistant peritonitis associated with peritoneal dialysis: a cause for
      concern.
AB  - BACKGROUND: Peritonitis resulting from peritoneal dialysis (PD) remains a serious
      cause of morbidity and even mortality among dialysis patients. AIM: To highlight
      the danger of antibiotic resistance in patients on dialysis who have received
      multiple courses of antibiotics. METHODS: Two cases are reported in which the
      patients developed peritonitis resistant to vancomycin. CONCLUSIONS: Multi-drug
      resistance is a growing danger. It is imperative to use the most appropriate
      antibiotics in the proper dosage. If infections persist, early removal of the
      catheters is essential. The use of antibiotics in PD patients needs to be
      limited. Sensitivity patterns of the cultured organisms must be monitored
      regularly as the lack of vigilance may help accelerate the development of the so
      called 'super bug' resistant to all antibiotics.

PMID- 11993596
TI  - Bilateral subclavian steal syndrome.
AB  - BACKGROUND: Bilateral atherosclerotic subclavian artery occlusion is rare. AIM:
      To describe the surgical treatment of a patient with symptomatic bilateral
      subclavian artery occlusion. METHODS: A midline sternotomy and bilateral aorto
      subclavian bypass was performed in a male with upper limb, exercise-induced
      vertigo. RESULTS: Postoperatively symptomatic improvement paralleled an increase
      in brachial systolic arterial blood pressure readings. CONCLUSION: Bypass
      grafting is the more durable option for subclavian artery occlusion, as
      angioplasty with or without stenting is associated with a higher rate of late
      stenosis.

PMID- 11993597
TI  - Medicine in Limerick and its neighbourhood.

PMID- 11993598
TI  - Gastrointestinal leiomyosarcomas.

PMID- 11993599
TI  - Medical dominance in public health: necessity or legacy?

PMID- 11993600
TI  - Extensive intracranial calcification.

PMID- 11993601
TI  - Pasteurella multocida osteomyelitis following a dog bite.

PMID- 11993602
TI  - Torsion of the gallbladder.

PMID- 11993603
TI  - Granulomatous vasculitis of the gallbladder.

PMID- 11993604
TI  - Recurrent gastrointestinal bleed.

PMID- 11993605
TI  - The limits of tamoxifen.

PMID- 11993606
TI  - Cluster headache sine headache: two new cases in one family.

PMID- 11993607
TI  - Cluster headache sine headache: two new cases in one family.
AB  - We report two cases of cluster headache sine headache occurring in a family of
      cluster headache sufferers. A 54-year-old female, suffered for 15 years from
      short-lasting, right-sided attacks of eye reddening, lacrimation, rhinorrea,
      palpebral oedema and miosis, seven to eight times per day, in periods of 20-30
      days. She did not experience headache, either with or without these phenomena.
      Her son suffers from periorbital, short-lasting, right-sided painful attacks
      accompanied by eye reddening, lacrimation, rhinorrea and nasal stiffnesss,
      occurring in periods of 30-35 days. Soon after the end of the current cluster
      period he still had daily attacks lasting 10-15 min, with the oculo-nasal
      autonomic phenomena only. The occurrence of cluster headache sine headache and
      cluster headache in the same family strongly suggests that the first condition is
      related to the cluster headache syndrome. Cluster headache sine headache should
      be considered as a subtype of the cluster headache syndrome.

PMID- 11993608
TI  - Occipital headaches stemming from the lateral atlanto-axial (C1-2) joint.
AB  - Studies in normal volunteers have demonstrated that the lateral atlanto-axial
      joints (C1-2) are capable of causing pain in the occiput, but few clinical
      studies have validated this source of occipital headache. The present study
      tested the null hypothesis that the lateral atlanto-axial joints are not a common
      source of occipital headache. Patients presenting with occipital pain underwent
      diagnostic blocks of their lateral atlanto-axial joints if they demonstrated
      clinical features presumptively suggestive of a C1-2 origin for their pain. Of 34
      patients investigated, 21 obtained complete relief of their headache following
      diagnostic blocks, indicating that a C1-2 source of occipital pain is not rare.
      The clinical features used to select patients for blocks, however, had a positive
      predictive value of only 60%. Further study of headaches from C1-2 seems
      justified in order to establish more definitively the prevalence of this
      condition and how it might become better recognized in practice.

PMID- 11993609
TI  - Migraine and the extrapyramidal system.
AB  - This review explores a large series of observations from clinical and
      experimental studies on the interactions between migraine and the extrapyramidal
      system (EPS). A critical appraisal of these data suggests that the EPS is somehow
      involved in migraine. However, primary involvement of the EPS in the
      pathophysiology of migraine, as hinted at by the apparent concomitance of
      migraine, extrapyramidal symptoms and diseases, as well as by the common
      involvement of neurotransmitters and pathways, cannot as yet be proven. On the
      other hand, the involvement of EPS in migraine may reflect its more general role
      in the processing of nociceptive information and/or may be part of the complex
      behavioural adaptive response that characterizes migraine.

PMID- 11993610
TI  - Efficacy, safety and tolerability of oral eletriptan in the acute treatment of
      migraine: results of a phase III, multicentre, placebo-controlled study across
      three attacks.
AB  - The efficacy, safety and tolerability of the 5-HT1B/D receptor agonist eletriptan
      (40 mg and 80 mg) in acute treatment of migraine was evaluated in a
      multinational, randomized, double-blind, parallel-group, placebo-controlled,
      three-attack study treating 1153 patients. In the initial attack, significantly
      more eletriptan patients reported headache relief and complete pain relief at 2 h
      vs. placebo (40 mg 62% and 32%, 80 mg 65% and 34%, placebo 19% and 3%; P <
      0.0001). Headache relief occurred faster after eletriptan, with more patients at
      both doses reporting relief 30 min (P < 0.01) and 1 h (P < 0.0001) after
      treatment than after placebo. There was a significantly lower recurrence rate
      with eletriptan 80 mg compared with placebo (P < 0.01). Adverse events for all
      treatments were generally mild or moderate and self-limiting. Eletriptan 40 mg
      and eletriptan 80 mg both appear to be effective and well-tolerated acute
      migraine treatments.

PMID- 11993611
TI  - Increased plasma nitrites in migraine and cluster headache patients in interictal
      period: basal hyperactivity of L-arginine-NO pathway?
AB  - Nitrite concentrations in plasma were investigated in a population of migraine
      and cluster headache patients and a group of healthy non-headache controls. A
      hundred migraine patients and 69 cluster headache patients in the interictal
      period, and 112 controls, were studied. Significantly higher nitrite
      concentrations were found in migraine patients, with and without aura, and
      cluster headache patients, in remission and cluster phase, than in controls.
      These findings suggest that a basal dysfunction in the L-arginine-NO pathway may
      be involved in the peripheral mechanisms predisposing subjects with neurovascular
      headaches to individual attacks.

PMID- 11993612
TI  - Effects of donitriptan on carotid haemodynamics and cardiac output distribution
      in anaesthetized pigs.
AB  - We investigated the effects of donitriptan, which possesses a uniquely high
      affinity and efficacy at 5-HT1B/1D receptors, on carotid and systemic
      haemodynamics in anaes thetized pigs. Donitriptan (0.16-100 microg kg(-1), i.v.)
      dose-dependently decreased total carotid blood flow and vascular conductance
      (maximum response: -25 +/- 3%). This effect was entirely due to a selective
      reduction in the cephalic arteriovenous anastomotic fraction (maximum response: -
      63 +/- 3%; ED50%: 92 +/- 31 nmol/kg); the nutrient vascular conductance
      increased. Donitriptan did not decrease vascular conductances in or blood flow to
      a number of organs, including the heart and kidneys; in fact, vascular
      conductances in the skin, brain and skeletal muscles increased. Cardiac output
      was slightly decreased by donitriptan, but this effect was confined to peripheral
      arteriovenous anastomoses. The haemodynamic effects of donitriptan were
      substantially reduced by the 5-HT1B/1D receptor antagonist GR127935. These
      results show that donitriptan selectively constricts arteriovenous anastomoses
      via 5-HT1B receptor activation. The drug should be able to abort migraine
      headaches and it is unlikely to compromize blood flow to vital organs.

PMID- 11993613
TI  - A neural network model of sensitization of evoked cortical responses in migraine.
AB  - Migraine patients show abnormalities of cerebral electrophysiology that manifest
      themselves mainly during the attack interval. Cortical-evoked potentials of
      migraineurs fail to habituate to repetitive presentations of visual stimuli, and
      the amplitude of components of their auditory cortical-evoked potentials have a
      higher dependence on the stimulus intensities than in healthy subjects. A
      computer model of a neural hetwork has been developed that is able to reproduce
      both these neurophysiological dysfunctions. It predicts a positive correlation
      between the magnitudes of both these dysfunctions. The model also offers an
      explanation of why mutations in the same ion channel gene with opposite
      consequences on channel function, e.g. P/Q Ca2+ channels in migraine, may lead to
      similar electrophysiological abnormalities.

PMID- 11993614
TI  - CGRP may play a causative role in migraine.
AB  - Calcitonin gene-related peptide (CGRP) has been detected in increased amounts in
      external jugular venous blood during migraine attacks. However, it is unknown
      whether this is secondary to migraine or whether CGRP may cause headache. In a
      double-blind crossover study, the effect of human alphaCGRP (2 microg/min) or
      placebo infused intravenously for 20 min was studied in 12 patients suffering
      from migraine without aura. Headache intensity was scored on a scale from 0 to
      10. Two patients were excluded due to severe hypotension and one because she had
      an infection. In the first hour median peak headache score was 1.0 in the
      halphaCGRP group vs. 0 in the placebo group (P < 0.01). During the following 11 h
      all patients experienced headaches after halphaCGRP vs. one patient after placebo
      (P = 0.0004). The median maximal headache score was 4 after CGRP and 0 after
      placebo (P = 0.006). In three patients after halphaCGRP, but in no patients after
      placebo, the delayed headache fulfilled the IHS criteria for migraine without
      aura. As intravenous administration of halphaCGRP causes headache and migraine in
      migraineurs, our study suggests that the increase in CGRP observed during
      spontaneous migraine attacks may play a causative role.

PMID- 11993615
TI  - Splitting of the body image as somesthetic aura symptom in migraine.
AB  - Splitting of the body image was illustrated as a somesthetic aura symptom in
      three of the 562 entries to the national Migraine Art competitions, confirming
      previous descriptions of this rare phenomenon in the migraine literature. In this
      type of self-experienced paroxysmal body schema disturbance, the own body is
      perceived as being split, usually in the mid-line, into two halves that may be
      displaced or separated from each other. Splitting of the body image most
      frequently applies to the migraine sufferer's head. The said phenomenon, the
      pathomechanisms of which are obscure, must not be confused with the visual
      illusion of illusory splitting.

PMID- 11993616
TI  - The clinical characteristics of new daily persistent headache.
AB  - New daily persistent headache (NDPH) is a subtype of chronic daily headache. The
      literature on NDPH is scant and its true aetiology is unknown. A retrospective
      chart review was carried out from a computerized database at the Jefferson
      Headache Centre from August 1997 to May 2000 to identify patients with NDPH using
      the Silberstein et al. criteria. Forty women and 16 men were identified. Age of
      onset ranged from 12 to 78 years. The peak age of onset was the second and third
      decade in women and the fifth decade in men. Eighty-two per cent of patients were
      able to pinpoint the exact day their headache started. Onset occurred in relation
      to an infection or flu-like illness in 30%. A prior headache history was found in
      38% of patients. A family history of headache was documented in 29%. The duration
      of daily headache ranged from 1.5 h to 24 h; 79% were continuous. Nausea occurred
      in 68% of patients, photophobia in 66%, phonophobia in 61%, and lightheadedness
      in 55%. Laboratory testing and neuroimaging in all patients was normal except for
      Epstein-Barr virus antibody titres, which were positive in 71% of seven patients
      tested, representing past infection. NDPH appears to be a female-predominant
      disorder, marked by a continuous daily headache with associated migrainous
      symptoms. Over 80% of patients could state the exact date their headache began.
      One-third of patients developed NDPH with a flu-like illness.

PMID- 11993617
TI  - Weight management and weight loss strategies of professional jockeys.
AB  - Jockeys are required to maintain very low body weight and precise weight control
      during competition. This study examined the weight loss and weight management
      strategies of professional horseracing jockeys in the state of Victoria,
      Australia. An anonymous, self-completed questionnaire was administered (55%
      response rate, n = 116). Almost half (43%) reported that maintaining riding
      weight was difficult or very difficult, with 75% routinely skipping meals. In
      preparation for racing, 60% reported that they typically required additional
      weight loss, with 81% restricting food intake in the 24 hours prior to racing.
      Additionally, sauna-induced sweating (29%) and diuretics (22%) were frequently
      employed to further aid in weight loss prior to racing. These rapid weight loss
      methods did not differ between the 51% of jockeys who followed a weight
      management plan compared to those who did not. The impact of these extreme weight
      loss practices on riding performance and health remains unknown.

PMID- 11993618
TI  - The effect of glycerol hyperhydration on olympic distance triathlon performance
      in high ambient temperatures.
AB  - The purpose of this study was to examine the effect of prior glycerol loading on
      competitive Olympic distance triathlon performance (ODT) in high ambient
      temperatures. Ten (3 female and 7 male) well-trained triathletes (VO2max = 58.4
      +/- 2.4ml kg(-1) min(-1); bestODTtime = 131.5 +/- 2.6 min) completed 2 ODTs (1.5
      km swim, 40-km bicycle, 10-km run) in a randomly assigned (placebo/ glycerol)
      double-blind study conducted 2 weeks apart. The wet-bulb globe temperature
      (outdoors) was 30.5 +/- 0.5 degrees C (relative humidity: 46.3 +/- 1.1%; hot) and
      25.4 +/- 0.2 degrees C (relative humidity: 51.7 +/- 2.4%; warm) for day 1 and day
      2, respectively. The glycerol solution consisted of 1.2 g of glycerol per
      kilogram of body mass (BM) and 25 ml of a 0.75 g x kg(-1) BM carbohydrate
      solution (Gatorade) and was consumed over a 60-min period, 2 hours prior to each
      ODT. Measures of performance (ODT time), fluid retention, urine output, blood
      plasma volume changes, and sweat loss were obtained prior to and during the ODT
      in both the glycerol and placebo conditions. Following glycerol loading, the
      increase in ODT completion time between the hot and warm conditions was
      significantly less than the placebo group (placebo 11:40 min vs. glycerol 1:47
      min; p < .05). The majority of the performance improvement occurred during the
      final 10-km run leg of ODT on the hot day. Hyperhydration occurred as a
      consequence of a reduced diuresis (p < .05) and a subsequent increase in fluid
      retention (p < .05). No significant differences were observed in sweat loss
      between the glycerol and placebo conditions. Plasma volume expansion during the
      loading period was significantly greater (p < .05) on the hot day when glycerol
      appeared to attenuate the performance decrement in the heat. The present results
      suggest that glycerol hyperhydration prior to ODT in high ambient temperatures
      may provide some protection against the negative performance effects of competing
      in the heat.

PMID- 11993619
TI  - Effect of high and low rates of fluid intake on post-exercise rehydration.
AB  - The effect of a high (H) and a low (L) rate of post-exercise fluid consumption on
      plasma volume and fluid balance restoration was investigated. Eight well-trained
      cyclists were dehydrated at 3% of body weight (BW) by cycling at 28 degrees C.
      During the recovery period, they ingested a carbohydrate-electrolyte solution in
      a volume equivalent to 120% of BW loss. Randomly, they ingested 60%, 40%, and 20%
      in the 1st, 2nd, and 3rd hours of the recovery period, respectively (H), or 24% x
      h(-1) during 5 hours (L). BW loss was similar for both trials and resulted in a
      total drink intake of 2.6 +/- 0.1 kg. Urine output in H exceeded significantly
      that of L in the 2nd and 3rd hours. This was reversed in the 5th and 6th hours.
      Plasma volume and fluid balance increased more rapidly in H compared to L. After
      6 hours this difference disappeared. It is concluded that H results in a faster
      rate of plasma volume and fluid balance restoration compared to L, despite a
      temporary large urine output.

PMID- 11993620
TI  - Reported eating behavior and attitudes improvement after a nutrition intervention
      program in a group of young female dancers.
AB  - The aim of the study was to evaluate the effectiveness of an intervention program
      that combined nutrition education and prevention of disordered eating in a group
      of female professional dance students. Thirty-two dancers, aged 19-25 years, took
      part in the program. Evaluation was done by a series of questionnaires that
      participants were asked to complete on 3 occasions. Assessments of body
      composition and dietary intake were also performed. Significant improvements in
      nutrition knowledge as well as a decrease in abnormal eating behavior and dietary
      restraint were observed at post intervention. At 6-month follow-up, the positive
      effects were maintained and further benefits were recorded; only nutrition
      knowledge showed a minor decline. Participants who were at higher risk for
      adopting abnormal eating behavior benefited the most from the program. These
      findings encourage the implementation of intervention programs in groups of young
      women that experience particular pressures for controlling body weight.

PMID- 11993621
TI  - Acute creatine supplementation and performance during a field test simulating
      match play in elite female soccer players.
AB  - This study investigated the effects of acute creatine (Cr) supplementation on the
      performance of elite female soccer players undertaking an exercise protocol
      simulating match play. On two occasions, 7 days apart, 12 players performed 5 x
      11-min exercise testing blocks interspersed with 1 min of rest. Each block
      consisted of 11 all-out 20-m running sprints, 2 agility runs, and 1 precision
      ball-kicking drill, separated by recovery 20-m walks,jogs, and runs. After the
      initial testing session, subjects were assigned to either a CREATINE (5 g of Cr,
      4 times per day for 6 days) or a PLACEBO group (same dosage of a glucose polymer)
      using a double-blind research design. Body mass (BM) increased (61.7 +/- 8.9 to
      62.5 < or = 8.9 kg, p < .01) in the CREATINE group; however, no change was
      observed in the PLACEBO group (63.4 < or = 2.9 kg to 63.7 +/- 2.5 kg). No overall
      change in 20-m sprint times and agility run times were observed, although the
      CREATINE group achieved faster post-supplementation times in sprints 11, 13, 14,
      16, 21, 23, 25, 32, and 39 (p <.05), and agility runs 3, 5, and 8 (p < .05). The
      accuracy of shooting was unaffected in both groups. In conclusion, acute Cr
      supplementation improved performance of some repeated sprint and agility tasks
      simulating soccer match play, despite an increase in BM.

PMID- 11993622
TI  - Energy balance during an ironman triathlon in male and female triathletes.
AB  - Energy balance of 10 male and 8 female triathletes participating in an Ironman
      event (3.8-km swim, 180-km cycle, 42.2-km run) was investigated. Energy intake
      (EI) was monitored at 7 designated points by dietary recall of food and fluid
      consumption. Energy expenditure (EE) during cycling and running was calculated
      using heart rate-VO, regression equations and during swimming by the multiple
      regression equation: Y = 3.65v+ 0.02W- 2.545 where Yis VO,in L x min(-1), v is
      the velocity in m s(-1), Wis the body weight in kilograms. Total EE (10,036 +/-
      931 and 8,570 +/- 1,014 kcal) was significantly greater than total EI (3,940 +/-
      868 and 3,115 +/- 914 kcal, p <.001) for males and females, respectively,
      although energy balance was not different between genders. Finishing time was
      inversely related to carbohydrate (CHO) intake (g x kg(-1) x h(-1)) during the
      marathon run for males (r = -.75,p <.05), and not females, suggesting that
      increasing CHO ingestion during the run may have been a useful strategy for
      improving Ironman performance in male triathletes.

PMID- 11993623
TI  - Mineral metabolism in male cyclists during high-intensity endurance training.
AB  - This study examined the effects of intense endurance training on basal plasma and
      24-hour urinary calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn), and copper
      (Cu) levels in 9 male competitive cyclists. The supervised training program
      followed a baseline period and included a volume phase (6 weeks, averaging 87% of
      maximal heart rate [HR(max)]), an interval phase (18 days, 100% of HR(max)), and
      a 10-day unloading taper. The primary training outcome measure was 20-km time
      trial cycling performance. Subjects ate unrestricted diets and maintained their
      weight. Compared to baseline, performance improved significantly (p < .05), while
      mineral metabolism was not significantly different after the volume phase.
      However, after the interval phase, renal Ca excretion increased (p < .05) and
      plasma Ca fell slightly below the clinical norm. As compared to the interval
      phase, urinary Ca decreased (p <.05), plasma Ca increased (p < .05), and
      performance further improved (p < .05) after the taper. Whereas Mg, Fe, Zn, and
      Cu metabolism remained unchanged throughout the study, greater renal Ca excretion
      was associated with very high intensity interval training.

PMID- 11993624
TI  - Macro- and micro-nutrient intake of adolescent Greek female volleyball players.
AB  - Adequate nutrition is critically important for the achievement of the adolescent
      athlete's optimal performance. The purpose of the present study was to evaluate
      the adequacy of macro- and micro-nutrients in the adolescent Greek female
      volleyball players' diet. The subjects of the study consisted of 16 players who
      were members of the Junior National Team (NP) and 49 players who participated in
      the Junior National Championship (CP). Dietary intake was assessed using a 3-day
      food record. Protein intake (16.0 +/- 4.9% of total energy intake) was
      satisfactory, whereas fat consumption (37.5 +/- 11.1%) was above recommended
      values and at the expense of carbohydrate intake (45.9 +/- 12.5%). There were no
      significant differences between NP and CP concerning the intake of
      macronutrients, except for the fat intake (when this is expressed in grams per
      day and grams per kilogram of body weight and the saturated fat intake, which
      were both higher in NP compared to CP players (p < .05). The mean energy intake
      was 2,013 +/- 971 and 1,529 +/- 675 kcal for NP and CP, respectively (p < .05).
      NP, in particular, consumed fat and especially saturated fatin orderto meet their
      energy needs. As for micronutrients, the volleyball players fell short of meeting
      the RDA values for calcium, iron, folic acid, magnesium, zinc, and vitamins A, B,
      B, and B2. There was no difference between NP and CP in micronutrient intake. In
      conclusion, subjects in the current study lacked proper nutrition in terms of
      quantity and quality.

PMID- 11993625
TI  - Effect of flavor and awareness of kilojoule content of drinks on preference and
      fluid balance in team sports.
AB  - A palatable flavor is known to enhance fluid intake during exercise; however, a
      fear of excessive kilojoule intake may deter female athletes from consuming a
      sports drink during training sessions. In order to examine this issue, we
      monitored fluid balance during 9 separate training sessions undertaken by junior
      elite female netball players (n = 9), female basketball players (n = 7), and male
      basketball players (n = 8). The beverages tested were water, a regular
      carbohydrate-electrolyte beverage (6.8% CHO, 18.7 mmol/L Na, 3.0 mmol/L K, 1,130
      kJ/L), and an identical tasting, low kilojoule electrolyte beverage (1% CHO, 18.7
      mmol/L Na, 3.0 mmoI/L K, 170 kJ/L). Each subject received each of the 3 drinks at
      3 separate training sessions, in a randomized, balanced order. Subjects were
      aware of the beverage provided. Change in body mass over the training session was
      used to estimate body fluid change, while voluntary fluid intake was determined
      from the change in weight of drink bottles used in each session. The overall
      fluid balance on drinks classified as regular, low kilojoule, and water was -11.3
      ml/h (95%CI -99.6 to 77.0), -29.5 ml/h (95%CI -101.4 to 42.5) and-156.4 ml/h
      (95%CI-215.1 to-97.6), respectively. Theresults indicate that, overall, better
      fluid balance was achieved using either of the flavored drinks compared to water.
      These data confirm that flavored drinks enhance fluid balance in a field
      situation, and suggest that the energy content of the drink is relatively
      unimportant in determining voluntary fluid intake.

PMID- 11993626
TI  - Energy balance and luteal phase progesterone levels in elite adolescent aesthetic
      athletes.
AB  - Menstrual abnormalities are associated with negative energy balance and reduced
      energy expenditure (REE). To examine this relationship in elite adolescent
      aesthetic athletes, 3 groups of females (aged 15-18 years) were studied: 10
      oligo/amenorrheic athletes (OA), 11 eumenorrheic athletes (EA), and 8 non-athlete
      controls (C). Components of energy balance, body composition, dietary restraint,
      pubertal maturation, and luteal phase salivary progesterone were assessed in all
      groups. Both groups of athletes had a later age of menarche and lower pubertal
      development score compared to the non-athletes (p < or = .05). With the exception
      of salivary progesterone (ng/ml; OA = 0. 15 +/- 0.01 <EA = 0.29 +/- 0.1 and C =
      0.30 +/- 0.13, p = .007), there were no differences between the athlete groups.
      Energy balance (kcal/d) in the OA group was lower (-290 +/- 677) compared to
      eitherEA (-5 +/- 461) or C ( 179 +/- 592) but did not reach significance (p
      =.24). Dietary energy intake and absolute REE (kcal/d) were not different among
      groups, despite detectable differences in reproductive status, and thus could not
      be attributed to differences in energy balance or REE.

PMID- 11993627
TI  - Changes to the TEF schemes can have significant impacts on regulation and
      management of PCDD/F and PCB.
AB  - The changes recommended by the World Health Organisation (WHO) to the toxic
      equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDD/F) and the recommendation to extend both the
      TEF scheme and the tolerable daily intake (TDI) to include "dioxin-like" PCB
      congeners have significant implications for regulators who have relied heavily on
      the International TEF (I-TEF) scheme in setting and monitoring limits and
      exposure to these compounds. This paper examines example data sets of sources,
      environmental concentrations, food and exposure to indicate likely changes in
      calculated toxic equivalent (TEQ) due to the recommended changes to TEFs. Many
      published data sets available do not provide congener specific data for PCDD/F
      which limits the ability to recalculate TEQs. There are even fewer congener
      specific data published to enable calculation of TEQs for the dioxin-like PCBs.
      In general TEQs calculated using the WHO scheme for emissions to air were found
      to show small increases (in the order of 1-10%) in comparison to the I-TEQ (for
      PCDD/F), some sludge samples showed substantial decreases (up to 70%). Levels in
      food and calculations of exposure showed that the change to TEFs for PCDD/F
      increased calculated exposure by 10-20% while the change to PCB TEFs decreased
      calculated TEQ attributable to PCB by 0-10%. The effects of including PCB in the
      overall TEQ and the changes to TEFs for PCDD/F substantially increase calculated
      TEQ exposure. Congener specific data should be presented to allow calculation of
      desired TEQ and the impact of the changes on emission limits, regulations on
      sludge use and environmental quality standards should all be carefully
      considered. The absence of data on emissions of dioxin-like PCB means that it is
      not possible to estimate with any certainty the impact on overall TEQ emissions
      of including the nominated PCB. Given the potential for confusion with the
      proliferation of TEFs and the extension to include both PCDD/F and PCB in the
      calculation of TEQs it is important that great care is taken to clearly express
      which compounds are included and which TEF scheme has been applied in each case.

PMID- 11993628
TI  - Dioxin reservoirs in southern Viet Nam--a legacy of Agent Orange.
AB  - In the isolated Aluoi Valley of central Viet Nam, very high levels of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) were measured in soil, fish fat, duck fat,
      pooled human blood and breast milk samples collected from A So village between
      1996 and 1999. The village was situated on a former military base occupied by US
      Special Forces between 1963 and 1966. TCDD was a contaminant of the herbicide
      "Agent Orange", aerially sprayed in the valley between 1965 and 1970, and stored
      at the A So base. Measured levels were lower near the sites of two other former
      US bases in the valley which had been occupied for shorter periods of time. In
      areas where Agent Orange had been applied by low-flying aircraft, levels of TCDD
      in soil, food and human samples were elevated, but lower than those near the
      three former US bases. We confirm the apparent food chain transfer of TCDD from
      contaminated soil to cultured fish pond sediments to fish and duck tissues, then
      to humans as measured in whole blood and breast milk. We theorize that the Aluoi
      Valley is a microcosm of southern Viet Nam, where numerous reservoirs of TCDD
      exist in the soil of former military installations south of the former
      demilitarized zone. Large quantities of Agent Orange were stored at many sites,
      used in ground and aerial applications, and spilled. TCDD, through various forms
      of soil disturbance, can be mobilized from these reservoirs after decades below
      the surface, and subsequently, introduced into the human food chain.

PMID- 11993629
TI  - Comparability of world-wide analytical data of PCDDs, PCDFs and non-ortho PCBs in
      samples of chicken, butter and salmon.
AB  - It was the primary objective of the present study to elucidate, from a chemical
      analytical point of view, the comparability of dioxin determinations and the
      consequences concerning the data on levels in food reported world-wide. To do so,
      an international intercalibration study on the determination of polychlorinated
      dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like PCBs in three
      natural food items was performed between March and June 2000. Samples of chicken,
      butter and salmon, collected in Norway, where sent to 42 laboratories and
      analysed for 20 PCDDs/PCDFs/non-ortho PCBs. The study generated congener-specific
      data for the three food matrixes both on wet weight and lipid basis. The reported
      data from 37 laboratories, in 15 countries, were statistically analysed in order
      to determine the congener-specific comparability as well as the comparability
      based on a toxic equivalency value (TEQ). Based on the reported data the mean
      relative standard deviations (mean RSD) for the WHO98-TEQDFP measurements were
      found to range from 36% to 57% the three foods. For chicken, the consensus level
      was 1.2 ppt TEQ on lipid basis, and the reported levels by 24 laboratories were
      between 0.53 and 2.2 ppt. For butter, the consensus was 0.55 ppt TEQ. 27
      laboratories reported levels from 0.18 up to 1.5 ppt. For the salmon, sample
      levels of 5.9 to 38 ppt TEQ (by 25 laboratories) was reported where 15 ppt was
      the consensus value. It can thus be concluded that the world-wide data on
      dioxins, at background levels in foods, are not direct numerically comparable due
      to inherent analytical reasons. Up to 50% deviations are expected when
      interlaboratory dioxin results for foods are compared.

PMID- 11993630
TI  - Characterization of dioxin exposure in firefighters, residents, and chemical
      workers in the Irkutsk Region of Russian Siberia.
AB  - The goal of this study was to characterize body burdens of polychlorinated
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated
      biphenyls (PCBs) in three groups of Siberians living in the Irkutsk Region of
      Russia. These groups included firefighters exposed to a mixture of toxic
      substances extinguishing a large fire at the Shelekhovo Cable Factory in 1992,
      chemical workers from the Khimprom chemical plant, and residents living in
      proximity to large chemical factories in Sayansk and Angarsk. Blood samples from
      all groups were obtained in the fall of 1998. Dioxin analyses of samples were
      performed in Germany, Canada, and in a Russian dioxin laboratory in Ufa,
      Bashkortostan Republic. The average levels of dioxin toxic equivalents (TEQs) are
      23.6 parts per trillion (ppt) total TEQ (PCDD/F only) in the disabled
      firefighters, 25.0 in the non-disabled firefighters, 28.7 in residents, and 45.6
      in the Khimprom workers blood. Two workers did have elevated total TEQs of 91.4
      and 102.2 ppt. Dibenzofurans and coplanar PCBs substantially contribute to the
      total elevated TEQ seen here. The average TEQs suggest levels of dioxin exposure
      in this part of the former Soviet Union not dissimilar to levels measured in
      industrialized countries of Europe and Northern America.

PMID- 11993631
TI  - Levels of dioxins and dibenzofurans in breast milk of women residing in two
      cities in the Irkutsk Region of Russian Siberia compared with American levels.
AB  - The presence of dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs) in
      human tissue, food, and environmental samples from Russia has been monitored
      since 1988 as part of a research collaboration between a number of countries
      including Finland, the United States, Germany, the former Soviet Union, and
      Canada. Although elevated TCDD and PnCDD levels have previously been found in
      blood of male and female Russian chemical manufacturing workers and in their
      children, dioxin levels in the general population have usually been found to be
      lower than in Americans and Europeans. This study continues earlier work in the
      Irkutsk region of Russian Siberia, where we report levels of dioxin,
      dibenzofurans, and PCBs in human milk samples taken from general population women
      living in the industrialized cities of Angarsk and Usolye-Sibirskoye, near Lake
      Baikal. Total polychlorinated dibenzo-p-dioxin (PCDD) toxic equivalents (TEQs)
      compared in this paper for the industrialized regions of Siberia, Ukraine, and
      the US are similar, ranging from 6.1 to 7 parts per trillion (ppt). Recent 1998
      milk samples from Angarsk and Usolye-Sibirskoye have total mean polychlorinated
      dibenzofuran (PCDF) TEQs of 10 and 21.7 ppt, respectively, with the other
      industrialized countries ranging from 2.3 to 6.7 ppt. Although dioxin-like PCBs
      were not measured for the city of Usolye-Sibirskoye (1998), total mean PCDD/F TEQ
      from Angarsk and Usolye-Sibirskoye (1998) were the two highest levels in this
      study, with 26.9 and 28.5 ppt, respectively, followed by 1993-1994 Ukraine
      samples with 24 ppt, 1989 Siberian samples with 13.6 ppt, and 1996 USA with 11.4
      ppt total TEQ. In this study, higher levels of dioxins are noted in milk from
      Angarsk and Usolye-Sibirskoye than found in earlier Russian studies, with mean
      levels also exceeding 1996 and 1999 US breast milk dioxin levels.

PMID- 11993632
TI  - Assessment of organotin pollution along the Polish coast (Baltic Sea) by using
      mussels and fish as sentinel organisms.
AB  - Levels of tributyltin (TBT) and its degradation products, mono- (MBT) and
      dibutyltin (DBT), as well as triphenyltin (TPT), were monitored in 10 stations
      along the Polish coast (Baltic Sea). Mussel-Mytilus edulis-and fish-Platichthys
      flesus-were used as sentinel organisms. The bioaccumulation patterns of butyltin
      and phenyltin compounds varied substantially. Butyltins were detected in mussel
      tissue from all the sampled stations. Among them, organisms from the Gulf of
      Gdansk showed the highest residues (68 ng/g w.w. as Sn) in conjunction with
      elevated TBT/DBT ratios, which suggest recent inputs of TBT in the area.
      Additionally, flatfish were sampled in the Gulf of Gdansk, and different tissues
      (liver, digestive tube and gills) were analyzed separately. TPT, although
      undetected in mussels, was always present in fish. The highest organotin
      concentration was observed in the liver (369 ng/g w.w. as Sn) of fish caught near
      Gdansk port. Relatively high concentrations were observed in digestive tube,
      which points out the ingestion of organotin contaminated food as an important
      uptake route of those compounds in P. flesus.

PMID- 11993633
TI  - Quantitative determination of 1 -hydroxypyrene in bovine urine samples using high
      performance liquid chromatography with fluorescence and mass spectrometric
      detection.
AB  - An analytical method was developed to determine quantitatively 1-hydroxypyrene
      (OHP) in bovine urine samples. The procedure includes an enzymatic hydrolysis to
      cleave the conjugated metabolite, an enrichment step using solid phase extraction
      with a non-polar rinse step and elution with dichloromethane. A final clean-up on
      silicagel was performed before high-performance liquid chromatography (HPLC)
      analysis and fluorescence detection. Alternatively, HPLC and electrospray
      ionization in the negative ion mode applying selective ion monitoring acquisition
      revealed to be a highly sensitive detection method allowing the quantitation of
      low pg of OHP in the urine samples. The method was successfully applied to the
      determination of OHP in bovine urine samples from animals living in urban and
      rural areas. Urine concentrations of OHP were significantly higher (median 8.6
      microg l(-1)) of bovines living close to a highway.

PMID- 11993634
TI  - Investigation of polychlorinated dibenzo-p-dioxins, dibenzo-p-furans and selected
      coplanar biphenyls in Scottish farmed Atlantic salmon (Salmo salar).
AB  - Farmed and wild Scottish Atlantic salmon were obtained from retail suppliers,
      producers, and Stirling University in Scotland during January, 1999, for
      determination of 17 2,3,7,8-C1-substituted PCDDs and PCDFs, and seven nonortho-
      and mono-ortho-PCBs. The study confirms previous reports of relatively high
      concentrations of PCDDs, PCDFs and, especially, PCBs in farmed Scottish salmon.
      The results indicate that high consumption of salmon, particularly by children
      under 5 years, could lead to intakes above the tolerable daily intake (TDI) and
      tolerable weekly intake (TWI) for these chemicals, especially the PCBs, when
      combined with mean or high level intakes from the typical UK diet. These results
      suggest further investigation of farmed salmon and salmon feed, including feed
      fortified with fish oil and feed fortified with selected vegetable oils, is
      warranted.

PMID- 11993635
TI  - PCDD/Fs and PCBs in airborne particulate matter of the greater Thessaloniki area,
      N. Greece.
AB  - Particle-bound polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and
      polychlorinated biphenyls (PCBs) were monitored at two sites in northern Greece
      for an eight-month period in 1999. PCDD/F concentrations were close to the lower
      end of reported values worldwide. Excepting a few cases, the PCDD/Fs homologue
      profile was stable. The gaseous PCDD/F fractions calculated were found to account
      for a small percentage of the total concentrations (<2% for OCDD/Fs and HpCDD/Fs,
      while 30-35% for TCDFs). Particle-bound PCBs were also found at low
      concentrations which, however, were higher at the urban site. Calculations of the
      dry deposition of particulate PCDD/ Fs and PCBs gave mean values of 0.52 and 0.59
      pg I-TEQ/m2/day of PCDD/Fs, while 242 and 74 pg/m2/day of sigmaPCBs for the urban
      and the semirural areas respectively. An anticorrelation of PCDD/F concentrations
      with ambient temperature was derived particularly for the lower chlorinated
      congeners. A weak association with winds of western and southern origin was also
      observed. Factor analysis and literature source profiles were employed to
      identify possible emission sources. It was appeared that the PCDD/F compositional
      pattern of TSP is influenced by mixed sources the most prominent being
      uncontrolled fires and car exhausts.

PMID- 11993636
TI  - Patterns of PCBs and PCDD/PCDFs in chicken and pork fat following a Belgian food
      contamination incident.
AB  - A food contamination incident involving polychlorobiphenyls (PCBs) and PCDD/Fs
      occurred in 1999 in Belgium. On heavily affected farms, concentrations of PCBs in
      chicken or pork fat exceeded the Belgium tolerance limit of 200 ng/g lipid weight
      for the sum of seven marker PCBs. Analysis of contaminated samples showed that
      the patterns for PCB and PCDD/F congeners differed among feed, chicken fat and
      pork fat. Lower chlorinated PCBs and polychlorodibenzofurans (PCDFs) including
      those with high TEFs (PCBs 105, 118, 126 and 2,3,4,7,8-PeCDF) were shown to
      either bioaccumulate more in chicken fat or to be eliminated more readily in
      pork. This leads to the possibility that consumption of chicken would result in a
      higher TEQ human body burden than that from the same consumption of pork. In
      addition, PCDF congeners with non-2,3,7,8-substitution (e.g., 1,2,4,7,8-PeCDF)
      were present in chicken fat but absent in pork fat. Since the residue pattern in
      this commercial episode changes less in the avian species, these results
      reinforce the value of birds rather than mammals as markers of the source of
      contamination with persistent organochlorine pollutants.

PMID- 11993637
TI  - Analysis of chlorinated paraffins in cutting fluids and sealing materials by
      carbon skeleton reaction gas chromatography.
AB  - Chlorinated paraffins (CPs) pose a major risk in the environment, due to their
      wide application, to their persistence, to their carcinogenic potential, and in
      view of the fact, that they cannot be easily identified. Various commercial
      cutting fluids and sealing materials were analysed for CPs with carbon skeleton
      reaction gas chromatography (GC) and flame ionization detection. CPs are
      simultaneously dechlorinated and hydrogenated to the corresponding alkanes with
      Pd catalyst material in the GC injector. With this method, the carbon chain
      length of commercial technical CPs was determined. In six of sixteen sealing
      materials we found five short and one medium chain length polychlorinated
      paraffins in percentages of 9-16% (w/w). In five cutting fluids we found
      predominantly medium to long chain length chloroparaffins with percentages of 2.5
      31% (w/w), only one fluid contained short chain CPs.

PMID- 11993638
TI  - Human biomonitoring of polychlorinated biphenyls and polychlorinated
      dibenzodioxins and dibenzofuranes in teachers working in a PCB-contaminated
      school.
AB  - Eighteen teachers from a highly contaminated school and 11 teachers from a
      control school participated in this study. Total polychlorinated biphenyl (PCB)
      indoor air concentration (six indicator congeners x 5) was beyond 12000 ng/m3 in
      some rooms of the contaminated school. PCB 28 and PCB 52 were the prevailing
      congeners. Whole blood was taken from each participant by the local health
      authority, pooled in two groups and analysed for the six PCB indicator congeners,
      non-ortho PCBs and polychlorinated dibenzodioxins (PCDD)/polychlorinated
      dibenzofurans (PCDF). Blood analysis showed elevated mean PCB 28 and PCB 52
      levels for the exposed group, however the two groups were almost identical with
      regard to PCB 101, 138, 153 and 180. Moreover no difference can be observed for
      the concentration of non-ortho PCBs and PCDD/PCDF. The data support the finding,
      that heavy indoor air contamination with low chlorinated PCBs causes an increase
      of PCB 28 and PCB 52 blood levels. However, this increment was small compared to
      their total PCB load.

PMID- 11993639
TI  - New perspectives in antibiotic prophylaxis for obstetric and gynaecological
      surgery.
AB  - The goals of antibacterial prophylaxis during obstetric/gynaecological surgery
      are similar to those of prophylaxis during intra-abdominal surgery. The vaginal
      flora consists of many aerobic and anaerobic organisms, is dominated by peroxide
      producing lactobacilli, and is non-pathogenic under normal conditions.
      Destabilization of the vaginal ecosystem, as in bacterial vaginosis (BV), causes
      a massive increase in the ratio of anaerobes to aerobes and is associated with a
      large increase in the risk of infection. The surgical procedures at most risk of
      postoperative infection are vaginal, abdominal and radical hysterectomy and
      caesarean section. Both the American College of Obstetricians and Gynecologists
      and the American Society of Health-System Pharmacists have recommended single
      dose prophylactic protocols using a variety of agents (penicillins,
      cephalosporins and clindamycin). However, it remains doubtful whether prophylaxis
      is used widely. In Italy, such prophylaxis has proved less effective in women
      with BV. Accordingly, patients with confirmed BV are given topical clindamycin
      for 7 days leading up to surgery, in addition to the usual prophylactic regimen.
      Caesarean delivery carries a 5- to 20-fold greater risk of infection that normal
      vaginal delivery. A meta-analysis of 66 clinical studies has shown that any
      prophylactic regimen is effective in reducing postoperative complications. The
      use of prophylaxis in patients undergoing a low-risk caesarean section remain
      controversial.

PMID- 11993640
TI  - New perspectives in antibiotic prophylaxis for intra-abdominal surgery.
AB  - Effective management of intra-abdominal infections requires a combination of
      preoperative preparation, antibiotic prophylaxis and appropriate surgical
      technique. Antibacterial prophylaxis should provide coverage of all likely
      pathogens, including aerobic and anaerobic organisms. Whereas antibacterial
      combination therapy is appropriate in certain situations, single-agent
      prophylaxis is appropriate for the majority of patients and ampicillin/sulbactam,
      with its broad-spectrum anti-aerobic/anti-anaerobic activity, is an attractive
      prophylactic option. Surgery involving the gastrointestinal tract provides a
      special challenge by virtue of its high, predominantly anaerobic, bacterial load.
      However, the requirement for prophylaxis varies depending upon the precise site
      of intervention. Biliary tract surgery requires prophylaxis in high-risk patients
      only, whereas hepatobiliary or pancreatic surgery requires prophylaxis in all
      patients. Gastroduodenal operations require prophylaxis in the presence of risk
      factors, such as abnormal gastric acidity or bleeding. Colorectal procedures
      present a high risk of anaerobic infection and sepsis, and require adequate
      prophylaxis combined with a thorough preoperative preparation designed to reduce
      considerably the bacterial load of the bowel. Where peritonitis does follow intra
      abdominal surgery, patients should receive antibacterial therapy commensurate
      with the risk of serious infection. A small proportion of patients will be at
      risk of severe infection and will require triple-agent therapy. However, most
      patients are likely to develop mild-to-moderate infections only and can be
      treated with a single, broad-spectrum antibiotic agent, such as
      ampicillin/sulbactam, a beta-lactam/beta-lactamase inhibitor.

PMID- 11993641
TI  - Surgical prophylaxis: the evolution of guidelines in an era of cost containment.
AB  - Postoperative infections account for a large proportion of hospital-acquired
      infections, are associated with a high morbidity and mortality, and place a large
      burden upon the inpatient healthcare budget. Prophylaxis is desirable and is
      based on a combination of preoperative preparation, surgical techniques,
      perioperative antibiotic prophylaxis and postoperative wound care. There is
      considerable evidence that antibiotics are used excessively and inappropriately
      in the prevention and treatment of hospital-acquired infections, including
      surgical-site infections. In the case of the latter, timing of prophylaxis is
      crucial to success yet antibiotics are often administered at the wrong time or
      for too long a period, with implications for the cost of patient care. Several
      studies have shown that the local implementation of practice guidelines can yield
      significant improvements in antibiotic use and the cost of surgical prophylaxis.
      More rational use of antibiotics is likely to benefit the treatment of future
      surgical patients by reducing the pressure to select for antibiotic-resistant
      bacterial pathogens.

PMID- 11993642
TI  - Surgical prophylaxis in practice.
AB  - The use of antibacterial prophylaxis of postoperative infections is firmly
      established within clean-contaminated procedures. For clean procedures,
      prophylaxis has traditionally been reserved for operations involving foreign-body
      implantation. However, evidence that postoperative infections from non-prosthetic
      clean procedures are highly under-reported suggests that prophylaxis is also
      advisable, at least for some non-prosthetic procedures, such as breast surgery
      and herniorrhaphy. Although cefazolin is recommended by current guidelines,
      cefuroxime and cefamandole have a broader antimicrobial spectrum and should be
      preferred in clean prosthetic surgery prophylaxis. In this type of surgery
      glycopeptides are not recommended for routine use but may have a role for major
      prosthetic implantation in units with a high incidence of methicillin-resistant
      staphylococci. In the case of clean-contaminated procedures, cefazolin is
      recommended for routine use, although colorectal procedures require an agent with
      improved anti-anaerobic activity. In addition, experience has shown that
      obstetric/gynaecological, gastroduodenal and biliary tract surgery and
      appendectomy all require broad-spectrum antibacterial prophylaxis. Suitable
      agents include cefoxitin, cefotetan, ureidopenicillins and beta-lactam/beta
      lactamase inhibitor combinations. The traditional surgical classification scheme
      needs to be replaced with a classification that additionally accounts for patient
      specific risk factors. The limitations of the current scheme may partly explain
      why current guidelines are so seldom followed in clinical practice.

PMID- 11993643
TI  - Application of capillary electrophoresis to the simultaneous determination of
      betaines in plants.
AB  - The simultaneous determination of betaines, the key compounds for osmotic
      regulation in plants, was established by capillary electrophoresis (CE). After
      four betaines, glycine betaine (GB), beta-alanine betaine (AB), proline betaine
      (PB), and 2-hydroxyproline betaine (HPB), were esterified with p-bromophenacyl
      bromide, the esters were electrophoresed in 100 mM sodium phosphate at pH 3.0. A
      low-pH condition in CE and esterification gave an advantage of resolving each of
      the ester peaks as well as those of the unreacted reagent and other components.
      Furthermore, the addition of 4% polyethylene glycol (PEG) gave a better
      resolution of 4 peaks, resulting in the separation of the overlapped peaks of PB
      and AB. It was found from the standard addition method being applied to barley
      leaves that the GB content in plants could be evaluated by using a calibration
      curve of the GB standard solution. The extraction of GB from plant leaves was
      also improved by adopting water as the extraction solvent instead of a mixture of
      organic solvents. The present method was suitably applied to actual plant
      specimens collected from a saline area of China.

PMID- 11993644
TI  - Liquid chromatographic determination of ornithine and lysine based on
      intramolecular excimer-forming fluorescence derivatization.
AB  - A highly sensitive and selective fluorometric determination method for ornithine
      and lysine has been developed. This method is based on an intramolecular excimer
      forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butyric
      acid N-hydroxysuccinimide ester (PSE), followed by reversed-phase liquid
      chromatography (LC). The analytes, containing two amino moieties in a molecule,
      were converted to the corresponding dipyrene-labeled derivatives by reaction with
      PSE. The derivatives afforded intramolecular excimer fluorescence (450-550 nm)
      which can clearly be discriminated from the normal fluorescence (370-420 nm)
      emitted from PSE and monopyrene-labeled derivatives of monoamines. The structures
      of the derivatives and the emission of excimer fluorescence were confirmed by LC
      with mass spectrometry and with three-dimensional fluorescence detection system,
      respectively. The PSE derivatives of ornithine and lysine could be separated by
      reversed-phase LC on ODS column with isocratic elution. The detection limits
      (signal-to-noise ratio = 3) for ornithine and lysine were 3.5 and 3.7 fmol,
      respectively, for a 20-microl injection. Furthermore, this method had enough
      selectivity and sensitivity for the determination of ornithine and lysine in
      normal human urine.

PMID- 11993645
TI  - Amperometric detection of superoxide dismutase at cytochrome c-immobilized
      electrodes: xanthine oxidase and ascorbate oxidase incorporated biopolymer
      membrane for in-vivo analysis.
AB  - Amperometric measurement of superoxide dismutase (SOD) was carried out at
      cytochrome c-immobilized monolayers and ascorbate oxidase (AOD)/xanthine oxidase
      (XOD)/cytochrome c- and (AOD, XOD)/cytochrome c-multilayers. Cytochrome c was
      covalently immobilized on mercaptopropionic acid-containing self-assembled
      monolayers on gold. A biopolymer membrane of poly-L-lysine confining XOD and AOD
      was cast on the monolayer of cytochrome c. While both the cytochrome c
      immobilized monolayer and multilayer electrodes show anodic current responses to
      the generation of superoxide radical, the sensitivity of the multilayer system
      for the detection of superoxide radical was high relative to that of the
      monolayer system. In the case of the cytochrome c-multilayer electrodes, the
      generation of superoxide radical near the sensing element, cytochrome c, resulted
      in high sensitivity for the detection of superoxide. The use of a XOD and AOD
      incorporated poly-L-lysine membrane enabled the detection of the generation of
      superoxide radical in the presence of L-ascorbic acid. Though L-ascorbic acid
      could scavenge superoxide radical, the biopolymer membrane confined with AOD will
      oxidize any L-ascorbic acid that permeated into the membrane. By using the
      multilayer electrodes, one could measure the activity of SOD in the presence of L
      ascorbic acid.

PMID- 11993646
TI  - Molecular-dynamics simulation for liquid chromatographic interactions: effect of
      mobile phase composition.
AB  - A molecular-dynamics simulation method has been applied to investigate the
      influence of the mobile-phase composition on the retention of solutes in HPLC.
      The distribution profiles of the distance between two atoms in ODS ligands were
      constructed to characterize the conformation of ODS ligand molecules. The
      distinct difference of ODS conformation is observed by comparing molecular models
      consisting of solvent molecules at each solvent composition. The distribution
      profiles of the distance between the mobile-phase solvent molecules and ODS
      ligand molecules were also constructed to characterize the distribution of the
      solvent molecules at each composition. In all distribution profiles, the
      difference in the distribution due to a change in the solvent compositions was
      very clearly found, and the facts seem to be very reasonable. The distribution
      profiles of the distance between the solute, n-propylbenzene, and the terminal
      carbon atom in the ODS ligand, and between the solute and the silicon atom in the
      ODS ligand have been also constructed to see the distribution of the solutes in
      the separation system. The calculated solute distribution in the ODS
      methanol/water system is very consistent with the actual chromatographic
      retention behaviors.

PMID- 11993647
TI  - Photo-responsive retention behavior of azobenzene-modified cyclodextrin
      stationary phase in micro-HPLC.
AB  - An azobenzene-modified gamma-cyclodextrin stationary phase (Az gamma-CDSP) was
      prepared and its photo- and temperature-responses for the retention of perylene
      and pentacene were investigated using a mixture of methanol and water as the
      mobile phase in micro-HPLC. The retention of perylene slightly increased, whereas
      that of pentacene significantly decreased by UV light irradiation to Az gamma
      CDSP. These retentions recovered upon irradiation with visible light. Both
      retentions decreased upon an increase in the column temperature. It was presumed
      that the trans-azobenzene moiety acts as a preventive cap for perylene and a
      spacing for pentacene in filling the CD cavity. An azobenzene-modified stationary
      phase changed its retention behavior with the column temperature and the light
      irradiation. An improvement in the micro-HPLC system and the optimization of the
      molecular structure of the photo-responsive stationary phase would provide
      selective retention control by the irradiation of light in micro-separation
      systems.

PMID- 11993648
TI  - Characterization of surface and photooxidative properties of supported metal
      oxide photocatalysts using solid-state NMR.
AB  - In situ solid-state NMR (SSNMR) methodologies have been used to investigate the
      surface properties and photooxidative reactivities of a number of metal oxide
      photocatalysts. Adsorption of ethanol on single monolayers of TiO2, SnO2, V205,
      and WO3 supported on porous Vycor glass results in the formation of hydrogen
      bonded ethanol species and metal-bound ethoxide species. The chemical shift of
      the metal-bound ethoxide species varies with the metal oxide catalyst while the
      chemical shift of the hydrogen-bonded species is independent of the metal oxide.
      X-ray powder diffraction, UV-VIS spectroscopy, and SSNMR investigations of
      ethanol adsorption show that increasing the number of monolayers of TiO2 on the
      Vycor surface changes the morphology of the catalyst from amorphous at a single
      monolayer coverage to anatase at a four monolayer coverage. The rate of
      photocatalytic oxidation of ethanol, acetone, and 2-propanol also increases with
      increasing TiO2 monolayer coverage.

PMID- 11993649
TI  - Confocal fluorescence microscope studies of the adsorptive behavior of
      dioctadecyl-rhodamine B molecules at a cyclohexane-water interface.
AB  - The capabilities of using a confocal fluorescence microscope (CFM) for the
      interface-selective observation of dye molecules at an oil-water interface were
      evaluated. A simple expression for a criterion of interface selectivity was
      derived. The adsorptive behavior of dioctadecyl-rhodamine B at a cyclohexane
      water interface was investigated experimentally to demonstrate the interface
      selective observation with a CFM. The minimum number of detectable molecules in
      the probe area at the interface was estimated to be 82 for the present system.
      Preliminary experimental results of co-adsorption systems composed of adsorbed
      dye molecules and charged surfactants are also presented.

PMID- 11993650
TI  - Broadband sum frequency generation with two regenerative amplifiers: temporal
      overlap of femtosecond and picosecond light pulses.
AB  - Sum frequency generation (SFG) spectroscopy is a valuable tool for studying
      interfaces such that the boundary between two adjoining phases can be probed with
      minimal interference from the adjacent bulk material. More recently, broad
      bandwidth sum frequency generation (BBSFG) techniques are being explored. This
      technique using IR broad-bandwidth fs pulses overlapped with narrow-bandwidth ps
      pulses to obtain BBSFG spectra is described. In the BBSFG system design presented
      here, the fs pulse and the ps pulse that are generated in separate regenerative
      amplifiers are overlapped temporally. This temporal overlap process is discussed.
      In addition, images of the sum frequency response demonstrate its viability. The
      new approach in experimental design described here for this emerging technology,
      BBSFG, has application for studying time-dependent processes at interfaces that
      inherently produce low SFG signal levels such as air-aqueous interfaces.

PMID- 11993651
TI  - Effect of the excitation source on the quantum-yield measurements of rhodamine B
      laser dye studied using thermal-lens technique.
AB  - A dual-beam transient thermal-lens technique was employed for the determination
      of absolute fluorescence quantum-yield measurements of Rhodamine B laser dye in
      different solvents. We investigated the effect of excitation on the absolute
      fluorescence quantum yield of Rhodamine B. 514 nm radiation from an argon ion
      laser was used as a cw excitation source and 532 nm pulses from a Q-switched
      Nd:YAG laser were used as a pulsed excitation source. The fluorescence quantum
      yield values were found to be strongly influenced by environmental effects as
      well as the transient nature of the excitation beam. Our results also indicate
      that parameters, like the concentration of the dye solution, aggregate formation
      and excited state absorption, affect the absolute values of the fluorescence
      yield significantly.

PMID- 11993652
TI  - Grazing-exit X-ray spectrometry for surface and thin-film analyses.
AB  - Electron-probe x-ray micro analysis (EPMA) and particle-induced x-ray emission
      analysis (PIXE) were performed under grazing-exit conditions. To control the exit
      angle (take-off angle), a new sample holder having a stepping motor was developed
      for grazing-exit EPMA. A carefully polished surface of a stainless-steal sample
      was measured. The surface of stainless steel is normally covered with a thin
      native oxide layer. The intensity ratio of Cr K(alpha) to Fe K(alpha) increases
      significantly at the grazing angle, becoming about 5-times larger at 0.2 degrees
      than at 40 degrees. This result indicates that grazing-exit EPMA is useful for
      surface analysis. In addition, a new PIXE equipment was developed for grazing
      exit x-ray measurements. The sample is fixed and the x-ray detector is moved by
      applying a linear stage. Preliminary experimental results of grazing-exit PIXE
      are also shown.

PMID- 11993653
TI  - X-ray absorption spectral analyses by theoretical calculations for TiO2 and Ni
      doped TiO2 thin films on glass plates.
AB  - Ni L- and Ti L-edge as well as Ti K-edge X-ray absorption experiments for TiO2
      thin films and Ni-doped TiO2 thin films coated on glass plates were performed
      using synchrotron radiation to investigate the structures around Ni and Ti ions
      in the films. The obtained spectra were compared with the results of theoretical
      calculations. It has consequently been found that the spectral features were
      affected by a change in the oxidizing form of Ni ions due to hydrogen reduction,
      by the charge variation and/or slight orbital splitting of Ti ions, and by the
      magnitude of the interaction between the center Ti ion and neighboring Ti ions.

PMID- 11993654
TI  - Fluorescence-quenching phenomenon by photoinduced electron transfer between a
      fluorescent dye and a nucleotide base.
AB  - Fluorescently labeled oligonucleotide probes have been widely used in
      biotechnology, and fluorescence quenching by the interaction between the dyes and
      a nucleobase has been pointed out. This quenching causes big problem in
      analytical methods, but is useful in some other cases. Therefore, it is necessary
      to estimate the fluorescence quenching intensity under various conditions. We
      focused on the redox properties of some commercially available fluorescent dyes,
      and investigated dye-nucleotide interactions between a free dye and a nucleotide
      in aqueous solution by electrochemical and spectroscopic techniques. Our results
      suggested that the quenching was accompanied by photoinduced electron transfer
      between a thermodynamically quenchable excited dye and a specific base. Several
      kinds of fluorescent dyes labeled to the 5'-end of oligonucleotide C10T6 were
      prepared, and their quenching ratios compared upon hybridization with the
      complementary oligonucleotide A6G10. The quenching was completely reversible and
      their efficiencies depended on the attached fluorophore types. The fluorescence
      of 5-FAM, BODIPY FL or TAMRA-modified probe was strongly quenched by
      hybridization.

PMID- 11993655
TI  - Measurement of dissolved oxygen based on enhanced cerium(IV) chemiluminescence.
AB  - The reaction of Ce(IV) with pyrogallol caused chemiluminescence, which was
      enhanced by dissolved oxygen. Dissolved oxygen in water was able to help in the
      determination by enhancing the chemiluminescence intensity. The limit of
      detection calculated from 3sigma was 43 micromol/dm3, and the relative standard
      deviation was 1.2% at 613 micromol/dm3 (n = 5). The results obtained for natural
      and tap water samples were compared with those provided by conventional methods;
      the agreement between them corroborated the usefulness of the proposed method.
      The chemiluminescence mechanism was studied by examining the effect of
      interference with Cl- and measuring the chemiluminescence spectrum. The
      chemiluminescence emitter, however, could not be identified.

PMID- 11993656
TI  - Derivative matrix isopotential synchronous fluorescence spectroscopy for the
      direct determination of 1-hydroxypyrene as a urinary biomarker of exposure to
      polycyclic aromatic hydrocarbons.
AB  - Urinary 1-hydroxypyrene is a biomarker in the measurement of human exposure to
      polycyclic aromatic hydrocarbons. A rapid and simple derivative isopotential
      synchronous fluorescence method was developed for the direct determination of 1
      hydroxypyrene in urine. A length of iso-intensity route was scanned on the three
      dimensional fluorescence spectrum of urine and this result was combined with that
      from derivative technique. Thus the strong background signals of urine were
      removed and the 1-hydroxypyrene can be determined directly in urine without
      tedious pre-separation. The derivative isopotential synchronous fluorescence
      spectrum was directly obtained from a single scan on a spectrofluorometer, which
      further simplified isopotential synchronous fluorescence technique. The
      recoveries of 93% to 115% were obtained for 1-hydroxypyrene added to urine.

PMID- 11993657
TI  - Electrochemical sensing for the determination of activated cyclic AMP-dependent
      protein kinase.
AB  - A novel electrochemical system has been developed for monitoring the cyclic AMP
      dependent protein kinase (PKA) activity. In this method, PKA activity was
      monitored as the change in the redox current of a ferrocene-pendant PKA substrate
      peptide (Fe-LRRASLG) on a gold electrode, which had been modified with thioctic
      acid, using cyclic voltammetry. The phosphrylation of the ferrocene-pendant
      substrate with PKA changed the net charge from +1 to -1. This caused a decrease
      in the redox current of the ferrocene unit due to an electrostatic repulsion
      between the substrate and the anionic surface of the electrode. We expect that
      this method is potentially useful for monitoring the enzyme activity in medical
      or pharmacological fields.

PMID- 11993658
TI  - Electrothermal vaporization on a tungsten filament for the determination of
      arsenic in chloride solutions by low-pressure helium ICP-MS.
AB  - A combined method of electrothermal vaporization and low-pressure helium ICP-MS
      was developed for the determination of traces of arsenic in chloride solutions,
      because serious spectral interference occurred in conventional argon ICP-MS. On a
      tungsten filament was placed 5 microl of a sample and heated electrothermally to
      remove the solvent. The resulting residue on the filament was covered with a
      vaporization chamber, and after reducing the pressure to ca. 5 Torr, it was
      rapidly heated by discharging a high-capacity condenser (0.22 F). The vapor of
      arsenic was transferred to a helium plasma with a stream of carrier gas for the
      determination. The background was not observed at m/z of 75, which allowed the
      determination of arsenic at ng/ml levels in chloride solutions. Sodium chloride
      significantly enhanced the intensity of the arsenic signal, whereas other
      chlorides, including KCl, MgCl2, CaCl2 and NH4Cl, suppressed the analytical
      signals. This enhancement due to sodium ions seems to be a peculiar phenomenon to
      the helium ICP. The proposed method can be applied to direct determinations of as
      low as 0.9 ng/ml of arsenic in seawater.

PMID- 11993659
TI  - Tungsten coil devices in atomic spectrometry: absorption, fluorescence, and
      emission.
AB  - In this work, tungsten coil (W-Coil) devices are used as atomizers for
      electrothermal atomization atomic absorption spectrometry (ETAAS), electrothermal
      atomization laser excited atomic fluorescence spectrometry (ETA-LEAFS), and
      electrothermal vaporization inductively coupled plasma atomic emission
      spectrometry (ETV-ICP-AES). For most cases in ETAAS and ETA-LEAFS, limits of
      detection (LODs) using the W-Coil are within a factor of ten of those observed
      with commercial graphite furnace systems. LOD for Cd by W-Coil AAS is 10 pg,
      while LODs for As, Se, Cr, Sb and Pb by W-Coil LEAFS are 950, 320, 1400, 330, and
      160 fg, respectively. The compact W-Coil device makes it an ideal atomizer for
      portable atomic spectrometry instrumentation, especially when coupled with a
      miniature charge coupled device spectrometer. Alternatively, the atomizer can be
      used as an inexpensive, modular add-on to an existing commercial ICP-AES system;
      and the thermal separation of Pb with interference elements Al, Mn, and Fe is
      demonstrated.

PMID- 11993660
TI  - Simple regression model using an optode for the simultaneous determination of
      zinc and cadmium mixtures in aqueous samples.
AB  - An optical-fiber chemical sensor (optode) is described for the simultaneous
      determination of Zn2+ and Cd2+ mixtures using 2-(5-bromo-2-pyridylazo)-5
      (diethylamino)phenol immobilized onto XAD-4 (Br-PADAP/XAD-4). A simultaneous
      analysis was achieved by using a single-wavelength kinetic approach coupled with
      a regression model. Here, the regression model was derived for the slope response
      of Br-PADAP/XAD-4 to binary mixtures of the metal ions, Zn2+ and Cd2+, at pH 8.
      The model was used then to predict the concentration of one metal ion while the
      other was kept constant. This was found to be reasonably successful for Zn2+ and
      Cd2+, with deviations of 3% and 10%, respectively. The sensor was also found to
      provide excellent sensitivity for both metal ions with excellent LODs (< 0.1 ppm)
      and very short analysis times (< 30 s).

PMID- 11993661
TI  - Spectrophotometric analysis of 5-coordinate cobalt(II) species for ligand
      substitution of hexakis(acetonitrile)cobalt(II) with bulky 1,1,3,3
      tetramethylurea in noncoordinating nitromethane.
AB  - The ligand substitution reaction of [Co(an)6]2+ (an = acetonitrile) with 1,1,3,3
      tetramethylurea (TMU) in the noncoordinating solvent, nitromethane, was
      spectrophotometrically investigated by titration. The observed spectral changes
      were analyzed using a model with the four steps of ligand substitution. The
      component complexes involved in the substitution were found to be 6-coordinate
      [Co(an)6]2+ and [Co(an)5(tmu)]2+, 5-coordinate [Co(an)3(tmu)2]2+ and
      [Co(an)2(tmu)3]2+, and 4-coordinate [Co(tmu)4]2+. The logarithmic values of the
      stepwise equilibrium constant are 2.17 +/- 0.26, 1.06 +/- 0.15, 1.19 +/- 0.06,
      and -0.4 +/- 0.4 at 25 degrees C. The decrease in the coordination number of the
      Co(II) ion from 6 to 5 during the formation of [Co(an)3(tmu)2]2+ and from 5 to 4
      during the formation of [Co(tmu)4]2+ is ascribed to the steric repulsion between
      the coordinating bulky TMU molecules.

PMID- 11993662
TI  - X-ray crystallographic approach to the design of phenolic schiff base reagents
      for the mutual separation of lanthanoids.
AB  - A novel mutual selectivity of lanthanoids in the N,N'-bis(5
      nitrosalicylidene)ethylenediamine (H2Nsalen)-KCl and N,N'-bis(5
      nitrosalicylidene)-o-phenylenediamine (H2Nsaloph)-KCl extraction systems was
      evaluated by the X-ray analysis of similar model complexes for extracted species.
      Cerium(IV) complexes with N,N'-bis(5-chlorosalicylidene)ethylenediamine
      (H2Clsalen), N,N'-bis(salicylidene)-o-phenylenediamine (H2saloph) and N,N'
      bis(3,5-dibromosalicylidene)-o-phenylenediamine (H2Br2saloph) were selected as
      the models. The result of the X-ray analysis suggested that [Ln(III)(Nsalen)2]-
      and [Ln(III)(Nsaloph)2]- are meridional type (two ligands are oriented
      perpendicular to each other) and sandwich type (two ligands are oriented parallel
      to each other), respectively. It was suggested that the selectivity of the
      meridional structure is superior to that of the sandwich structure in these
      extraction systems.

PMID- 11993663
TI  - Spectrophotometric characterization of diazacrown ethers having two
      carbodithioate groups.
AB  - Diazacrown ethers having two carbodithioate groups were synthesized, and their
      spectrophotometric properties were studied. Diammonium 1,4,10,13-tetraoxa-7,16
      diazacycrooctadecane-N,N'-bis(carbodithioate) (DA18CC) and ammonium 1,4,10-trioxa
      7,13-diazacycropentadecane-N,N'-bis(carbodithioate) (DA15CC) reacted with most
      heavy-metal ions through their two carbodithioate groups, and also reacted with
      alkali-metal ions or alkaline earth-metal ions through their diazacrown rings.
      Although the UV-VIS absorption spectra of DA18CC and DA15CC were hardly
      influenced by the addition of alkali-metal ions or alkaline earth-metal ions, the
      spectra of some heavy-metal chelates of DA18CC and DA15CC were influenced. The
      composition ratio (metal:ligand) of Cu(II) and Pb(II) chelates of DA18CC and
      DA15CC was altered from 1:1 to 1:2 by the addition of alkali-metal ions or
      alkaline earth-metal ions. It is suggested that the change in the absorption
      spectra and the composition ratio of the chelates can be attributed to an
      alteration of the equilibrium among species of the heavy-metal chelates of DA18CC
      and DA15CC due to the coordination of alkali-metal ions or alkaline earth-metal
      ions into the diazacrown ring.

PMID- 11993664
TI  - Detection of chlorophyll d' and pheophytin a in a chlorophyll d-dominating
      oxygenic photosynthetic prokaryote Acaryochloris marina.

PMID- 11993665
TI  - The possibility of regulating the species composition of marine phytoplankton
      using organically complexed iron.

PMID- 11993666
TI  - Voltammetric detection of lectin using sugar labeled with electroactive
      substance.
AB  - The voltammetric detection of soybean agglutinin (SBA) was investigated on the
      basis of an interaction between the lectin and a sugar. Because galactose and
      lactose combined with SBA, the sugars were labeled by a Schiff base with an
      electroactive daunomycin. After the labeled sugar and SBA were mixed,
      measurements were carried out by voltammetry. When SBA-sugar binding occurs, a
      part of daunomycin of the labeled sugar is taken to the binding sites. As a
      result, SBA is detected by a change in the peak current of daunomycin, and the
      SBA-sugar interaction is evaluated. The length of the alkyl chain between
      daunomycin and the sugar was also considered. The electrode response to the
      concentration of SBA was linear over the range of 0.04-0.8 microg min(-1). The
      merits of this procedure are the convenient preparation of labeled sugar and a
      rapid measurement without separation. On the other hand, the detection of sugar
      at the 10(-9) mol dm(-3) level was achieved by a competitive reaction to limited
      binding sites of the lectin between the sugar and the labeled sugar.

PMID- 11993667
TI  - Use of an ion-exchange membrane for sample pretreatment of ion chromatography:
      determination of phosphate ion and sulfate ion in deep subsurface water.

PMID- 11993669
TI  - Thermodynamic consideration for solvent effects in the synergistic extraction of
      europium(III) with pivaloyltrifluoroacetone and 1,10-phenanthroline.

PMID- 11993668
TI  - Simultaneous determination of fluorine and chlorine in rocks by ion
      chromatography in combination with alkali fusion and cation-exchange
      pretreatment.

PMID- 11993670
TI  - Violet diode laser for metal ion determination by capillary electrophoresis-laser
      induced fluorescence.

PMID- 11993671
TI  - A novel flow injection technique: all injection analysis.

PMID- 11993672
TI  - Atomic XAFS for a bromide ion bound on anion-exchange resin in water.

PMID- 11993673
TI  - Fabricating and imaging carbon-fiber immobilized enzyme ultramicroelectrodes with
      scanning electrochemical microscopy.
AB  - The scanning electrochemical microscope (SECM) is used to image the activity of
      enzymes immobilized on the surfaces of disk-shaped carbon-fiber electrodes. SECM
      was used to map the concentration of enzymatically produced hydroquinone or
      hydrogen peroxide at the surface of a 33-microm diameter disk-shaped carbon-fiber
      electrode modified by an immobilized glucose-oxidase layer. Sub-monolayer
      coverage of the enzyme at the electrode surface could be detected with micrometer
      resolution. The SECM was also employed as a surface modification tool to produce
      microscopic regions of enzyme activity by using a variety of methods. One method
      is a gold-masking process in which microscopic gold patterns act as mask for
      producing patterns of chemical modification. The gold masks allow operation in
      both a positive or negative process for patterning enzyme activity. A second
      method uses the direct mode of the SECM to produce covalently attached amine
      groups on the carbon surface. The amine groups are anchors for attachment of
      glucose oxidase by use of a biotin/avidin process. The effect of non-uniform
      enzyme activity was investigated by using the SECM tip to temporarily damage an
      immobilized enzyme surface. SECM imaging can observe the spatial extent and time
      course of the enzyme recovery process.

PMID- 11993674
TI  - Parameters important in fabricating enzyme electrodes using self-assembled
      monolayers of alkanethiols.
AB  - The fabrication of enzyme electrodes using self-assembled monolayers (SAMs) has
      attracted considerable interest because of the spatial control over the enzyme
      immobilization. A model system of glucose oxidase covalently bound to a gold
      electrode modified with a SAM of 3-mercaptopropionic acid was investigated with
      regard to the effect of fabrication variables such as the surface topography of
      the underlying gold electrode, the conditions during covalent attachment of the
      enzyme and the buffer used. The resultant monolayer enzyme electrodes have
      excellent sensitivity and dynamic range which can easily be adjusted by
      controlling the amount of enzyme immobilized. The major drawback of such
      electrodes is the response which is limited by the kinetics of the enzyme rather
      than mass transport of substrates. Approaches to bringing such enzyme electrodes
      into the mass transport limiting regime by exploiting direct electron transfer
      between the enzyme and the electrode are outlined.

PMID- 11993675
TI  - A glass capillary ultramicroelectrode with an electrokinetic sampling ability.
AB  - A glass capillary ultramicroelectrode (tip diameter approximately 1.2 microm)
      having an electrokinetic sampling ability is described. It is composed of a
      pulled glass capillary filled with an inner solution and three internal
      electrodes (Pt working and counter electrodes and an Ag/AgCl reference
      electrode). The voltammetric response of the capillary electrode is based on
      electrokinetic transport of analyte ions from the sample solution into the inner
      solution across the conical tip. It was found that the electrophoretic migration
      of analytes at the conical tip is faster than electroosmotic flow, enabling
      electrokinetic transport of analyte ions into the inner solution of the
      electrode. By using [Fe(CN)6]4- and (ferrocenylmethyl)trimethylammonium (FcTMA+)
      ions as model analytes, differential pulse voltammetric responses of the
      capillary electrode were investigated in terms of tip diameter of the capillary,
      sampling voltage, sampling time, detection limit and selectivity. The magnitude
      of the response depends on the size and charge of analyte ions. With a capillary
      electrode having a approximately 1.2-microm tip diameter, which minimizes non
      selective diffusional entry of analytes, the response after 1 h sampling at +1.7
      V is linearly related to [Fe(CN)6]4- concentration in the range of 0.50-5.0 mM
      with the detection limit of 30 microM. Application of a potential of the same
      sign as that of the analyte ion forces the analyte to move out from the electrode
      to the solution, enabling reuse of the same capillary electrode. The charge
      selective detection of analytes with the capillary electrode is demonstrated for
      [Fe(CN)6]4- in the presence of FcTMA+.

PMID- 11993676
TI  - Voltammetric studies of antimony ions in soda-lime-silica glass melts up to 1873
      K.
AB  - The half wave potential of reduction of Sb5+ in 16Na2O x 10CaO x 74SiO2 glass
      melts was examined by differential pulse voltammetry up to 1873 K. The half wave
      potential shifted to the positive direction with an increase in temperature. The
      results indicate that the equilibrium of Sb5+/Sb3+ shifted to negative direction
      with an increase in temperature. The half wave potential shifted to positive
      direction (48 mV at 1473 K) when the atmosphere over the melts changed from pure
      oxygen gas to air, in agreement with the theoretical prediction. The
      reversibility of Pt:O2 reference electrode is confirmed.

PMID- 11993677
TI  - Electrode reaction of Pu3+/Pu couple in LiCl-KCl eutectic melts: comparison of
      the electrode reaction at the surface of liquid Bi with that at a solid Mo
      electrode.
AB  - The electrode reaction of Pu3+/Pu couple at the interface between LiCl-KCl
      eutectic melt containing PuCl3 and liquid Bi phase was investigated by cyclic
      voltammetry at 723, 773 and 823 K. For comparison, the system was also studied
      using a solid Mo electrode in place of the liquid Bi electrode. It was found that
      the electrode reaction of Pu3+/Pu couple at the Bi electrode was almost
      reversible. The redox potentials of Pu3+/Pu couple at the liquid Bi electrode in
      the LiCl-KCl eutectic melt containing 0.87 wt% PuCl3 (0.0014 mole fraction) at
      723, 773 and 823 K were observed to be more positive by 0.575, 0.572 and 0.566 V,
      respectively, than those at the Mo electrode. These differences in potential were
      thermodynamically analyzed by assuming a lowering of the activity of Pu in Bi
      phase according to the alloy formation of PuBi2.

PMID- 11993678
TI  - Electrolyte effects on electrochemical properties of osmium complex polymer
      modified electrodes.
AB  - The electrolyte effects on the electrochemical behaviors of osmium complex
      polymer modified electrodes were investigated by a comparison between two osmium
      complexes, [Os(bpy)2(PVI)10Cl]Cl (Os-PVI10) and [Os(bpy)2(PVP)10Cl]Cl (Os-PVP10).
      The electrode process at Os-PVI10 modified electrodes is reaction-controlled,
      while a diffusion-controlled electrode process exists at Os-PVP10 modified
      electrodes. Both the cation and anion in supporting electrolytes strongly affect
      their electrochemical behaviors, such as the redox potential, wave shape and peak
      current. These phenomena are attributed to a change in the film structure and
      polymer swelling in various supporting electrolytes. The influence of electrolyte
      anions on the electrochemical behaviors is related to their hydrophobicity. The
      electrode process of Os-PVP10 depends on the pH value of solutions, exhibiting
      different electron transfer mechanisms.

PMID- 11993679
TI  - Ion-transfer voltammetry of local anesthetics at an organic solvent/water
      interface and pharmacological activity vs. ion partition coefficient
      relationship.
AB  - The ion-transfer reaction of local anesthetics at an organic solvent/water
      interface has been studied using cyclic voltammetry (CV) with a stationary
      nitrobenzene (NB)/water (W) interface. Procaine and seven other local anesthetics
      gave reversible or quasi-reversible voltammograms at the NB/W interface in the pH
      range between 0.9 and 9.6. These drugs are present in aqueous solution in either
      neutral or ionic form, or both forms. The half-wave potential, as determined by
      the midpoint potential in CV, vs. pH curves, were determined and analyzed to
      determine the partition coefficients of both neutral and ionic forms of the drugs
      between NB and W. The partition coefficients of the ionic forms were derived from
      their formal potential of transfer at an NB/W interface. The dissociation
      constants of ionic forms of the drugs in NB were also deduced. A high correlation
      between the pharmacological activity and the partition coefficient of the ionic
      form of amide-linked local anesthetics has been shown.

PMID- 11993680
TI  - Evaluation of ionic pollutants of acid fog and rain using a factor analysis and
      back trajectories.
AB  - Fog and rain water samples were collected at the same time in the Akita
      Hachimantai mountain range in northern Japan from June to September in 1998 and
      1999. The various ion concentrations in these samples were analyzed, and the fog
      droplet sizes were measured for each fog event. As the fog droplet size
      increased, the ion concentration decreased. The slope of log-log plots of the
      concentration versus the droplet size differed with the kind of ion. In order to
      characterize the air pollutant, moreover, these data were quantitatively analyzed
      by an oblique rotational factor analysis. We found that three factors were
      extracted as the air pollutant source: (NH4)2SO4, acids (HNO3 + H2SO4) and sea
      salt. Combining the factor analysis with the 72 h back-trajectory at 850 hPa
      level, we found that the contribution of each factor varied with the transport
      pattern of air masses.

PMID- 11993681
TI  - Chemical characterization of organic carbon dissolved in natural waters using
      inorganic adsorbents.
AB  - Dissolved organic carbon (DOC) in water samples from Lake Biwa was chemically
      characterized by two inorganic adsorbents with completely different surface
      characteristics. The two adsorbents were HIO (hydrous iron oxide) and SG (silica
      gel). Solutions of reference standard materials were analyzed concerning their
      adsorption behavior to HIO and SG for bovine serum albumin (BSA), fulvic acid
      extracted from the bottom sediments of Lake Biwa, phthalic acid, and starch. The
      adsorption of DOC to HIO was mainly controlled by ligand exchange and
      electrostatic interaction; that of SG was by electrostatic interaction. It was
      found that in a weak acid solution of around pH 5, BSA adsorbs to both HIO and
      SG, but that fulvic acid, phthalic acid and starch only show adsorption to HIO.
      Using these characteristics, DOC samples in natural water samples were
      characterized into pro-DOC, which adsorbs to both HIO and SG at pH 5, and car
      DOC, which only adsorbs to HIO at pH 5. The DOC samples in Lake Biwa on October
      7, 1997, at sampling sites Nb-2 and Nb-5 (south basin of Lake Biwa, the depths
      were about 2 and 4 m), and Ie-1 (north basin of Lake Biwa, the depth was about 75
      m) were characterized. The pro-DOC has different values, depending on their
      sampling sites and depths, and had the maximum value of 0.42 mg C l(-1) at the
      surface water of Ie-1, and had the lowest values at middle to deeper water depths
      (0.18-0.27 mg C l(-1)). The car-DOC showed a relatively stable value at Ie-1
      regardless of the depth (0.63-0.83 mg C l(-1)), and the maximum value was
      observed in Nb-2 and Nb-5 (1.2 and 1.3 mg C l(-1)). The ratios between car-DOC
      and pro-DOC concentrations were 0.2-0.5, and had different values for different
      sampling sites and depths. The ratios were significantly different for surface
      water samples where the biological activities are high and for bottom water
      samples where decomposition predominates.

PMID- 11993682
TI  - Distinguishing of linkage isomers of lactotetra oligosaccharides by using the
      relative ion intensity analysis of post-source decay fragment ions in curved
      field reflectron matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - The native oligosaccharides of lacto-N-neotetraose (Gal beta1-4GlcNAc beta1-3Gal
      beta1-4Glc; LNnT) and lacto-N-tetraose (Gal beta1-3GlcNAc beta1-3Gal beta1-4Glc;
      LNT) were analyzed by using curved-field reflectron matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Since a
      curved-field reflectron TOFMS enables a simultaneous focusing of a wide mass
      range of metastable fragment ions, the relative ion intensities in the post
      source decay (PSD) mass spectra can be discussed. The PSD mass spectra of LNnT
      and LNT were distinguishable in their relative ion intensities. In the case of
      LNT, beta-elimination could occur in the N-acetyl glucosamine (GlcNAc) at the C-3
      position, which was bonded by galactose (Gal); however, it did not occur in LNnT.
      The 3-O elimination caused a difference in the relative ion intensities in the
      PSD mass spectra of LNnT and LNT. The beta1-3 glycosyl linkage cleaved more
      easily than the beta1-4 glycosyl linkage in the MALDI-PSD fragmentation. An
      analysis of the relative ion intensities in the MALDI-PSD mass spectra of
      oligosaccharides was very useful for distinguishing the linkage isomers and for
      characterizing the types of glycosyl linkages.

PMID- 11993683
TI  - Integrated multilayer flow system on a microchip.
AB  - We utilized microchip technology and found that the multilayer flow of liquids
      can be formed in microchannels. Liquid/liquid interfaces were formed parallel to
      the side wall of the microchannels, because the surface tension and friction
      force are stronger than the force of gravity. A water/ethylacetate/water
      interface was formed in a 70-microm-wide and 30-microm-deep channel. The
      interface was observed to be quite stable and to be maintained for a distance of
      more than 18 cm. As an example of a multilayer flow application, we demonstrated
      the liquid/liquid extraction of Co-dimethylaminophenol complex in a microchannel.
      The solvent-extraction process of the complex into m-xylene in the multilayer
      flow was found to reach equilibrium in 4 s, while it took 60 s in a simple two
      phase extraction.

PMID- 11993684
TI  - Highly sensitive and direct detection of DNA fragments using a laser-induced
      capillary vibration effect.
AB  - A pulsed laser-induced stationary wave capillary vibration detection method was
      applied to the sensitive detection of capillary gel electrophoresis, and the
      direct detection of non-labeled nucleic acids, such as DNA sequencing products,
      was demonstrated. An excimer laser operating at 248 nm was used as a CVL
      excitation source, and polynucleotides were sensitively detected without
      derivatization. From an investigation on the endurance of several matrixes to
      pulsed laser irradiation, a polyacrylamide without a cross-linker (0%C) was found
      to have adequate endurance, and it exhibited no serious damage during an
      analysis. A cytosine-terminated sequence reaction product was detected with a
      sensitivity close to that of laser-induced fluorometry (LIF). These results
      suggest the feasibility of the highly sensitive detection of ultramicro amounts
      of biological materials without a pre- or post-column derivatization, which has
      usually been required in sensitive detection procedures, such as LIF.
      Furthermore, the feasibility of a novel DNA sequencing method is also suggested.

PMID- 11993685
TI  - Non-aqueous capillary electrophoresis of p-quinone anion radicals.
AB  - The electrophoretic detection of two kinds of p-quinone anion radicals arising
      from the electrolysis of benzoquinone and chloranil was achieved by employing an
      acetonitrile medium. Sufficient dehydration of a running solution was necessary
      for the detection of the benzoquinone anion radical. Oxygen in the running
      solution also caused a serious decrease in the amount of the benzoquinone anion
      radical during electrophoresis. The addition of methanol as a hydrogen-donor
      decreased the electrophoretic mobility of the benzoquinone anion radical
      significantly, while that of the chloranil anion radical was little changed. This
      result is interpreted in terms of hydrogen-bonding interaction between the p
      quinone anion radicals and methanol, reflecting the magnitude of their proton
      accepting ability (benzoquinone anion radical > chloranil anion radical).

PMID- 11993686
TI  - Neuroectodermal and neuroendocrine tumors principally seen in children.
AB  - Neuroectodermal tumors comprise a large proportion of childhood neoplasms.
      Neuroblastic tumors, including neuroblastoma, ganglioneuroblastoma, and
      ganglioneuroma, are the most frequent extracranial solid cancers of childhood,
      occurring primarily in infants and toddlers. Primitive neuroectodermal tumors,
      including Ewing sarcoma and peripheral neuroepitheliomas, occur most frequently
      in older children and adolescents, and as pediatric sarcomas are second in
      frequency only to rhabdomyosarcomas. Rarer neuroectodermal tumors include
      desmoplastic small cell tumors, esthesioneuroblastomas, and melanotic
      neuroectodermal tumors, the first two entities occurring as rather site-specific
      lesions in the abdomen and nose, respectively. Diagnosis can be difficult due to
      the undifferentiated nature of many of these cancers, but ancillary studies,
      including electron microscopy, immunohistochemistry, cytogenetics, and molecular
      genetics, enhance their recognition. The molecular nature of childhood
      neuroectodermal tumors is as diverse as their histology, ranging from the fusion
      genes characterizing the Ewing sarcoma family of tumors to the proto-oncogene
      amplification seen in aggressive neuroblastomas.

PMID- 11993687
TI  - Neuroendocrine neoplasms of the mediastinum.
AB  - Neuroendocrine neoplasms of the mediastinum form part of a family of tumors
      characterized by genotypic, immunophenotypic, and functional properties of
      neuroendocrine differentiation. Although rare, these tumors have been the source
      of much attention and controversy in the literature. Their nomenclature and
      classification, in particular, have continued to evolve over the years. Such
      tumors comprise lesions derived from neuroendocrine elements within the thymus,
      from paraganglionic rests, or from misplaced embryonal structures within the
      mediastinum. The most common neuroendocrine neoplasms of this anatomic region,
      however, correspond to neuroendocrine carcinomas of the thymus. The light
      microscopic, immunohistochemical, and ultrastructural features of these tumors
      are reviewed along with the advances in our understanding of these lesions and
      current trends in nomenclature and terminology.

PMID- 11993688
TI  - Pancreatic neuroendocrine neoplasms: a current summary of diagnostic, prognostic,
      and differential diagnostic information.
AB  - Pancreatic endocrine tumors (PETs) continue to be challenging diagnostic and
      prognostic lesions in surgical pathology and clinical medicine. These neoplasms
      can be graded into 1 of 3 tiers, based on histologic characteristics in likeness
      to epithelial neuroendocrine tumors in other anatomic sites. However, grade 1
      tumors are by far the most common and are the most difficult to prognosticate.
      The most helpful features by which to gauge the behavior of such lesions include
      size (3 cm or larger); mitotic activity (2 or more mitoses per 10 high-power
      [x400] microscopic fields); marked nuclear atypia, especially with atypical
      mitoticfigures; predominant tumor synthesis of gastrin, vasoactive intestinal
      polypeptide, somatostatin, glucagon, calcitonin, or adrenocorticotropic hormone;
      complete nonfunctionality of the tumor at an immunohistochemical level; or
      invasion of blood vessels, nerves, or adjacent organs by the neoplasm.
      Differential diagnosis of PETs includes lesions such as solid-pseudopapillary
      neoplasms, acinar carcinomas, metastatic neuroendocrine tumors, and
      plasmacytomas.

PMID- 11993689
TI  - Tumors of the autonomic nervous system.
AB  - Tumors of the adrenal medulla, extra-adrenal paraganglia of the sympathetic
      neuroendocrine system, and paraganglia of the head and neck are derivedfrom
      neural crest cells. These tumors manifest as growing masses and can cause
      endocrine dysfunction due to unregulated secretion of hormones. Tumors arising in
      the adrenal medulla (pheochromocytomas) and extraadrenal paraganglia
      (paragangliomas) usually present in adulthood. Their diagnosis is based on
      histologic features, immunohistochemical stains, and electron microscopy. These
      features are reviewed, as are familial syndromes and their associated gene
      mutations.

PMID- 11993690
TI  - The neuroendocrine system and its tumors: an overview.
AB  - Neuroendocrine tumors comprise a family of neoplasms with a wide range of
      morphologic, functional, and behavioral characteristics. Their diagnosis depends
      on the recognition of characteristic morphologic features and on the presence of
      markers indicative of neuroendocrine differentiation. Neuroendocrine tumors can
      be grouped into epithelial and neural subtypes on the basis of the presence of
      cytokeratins or neurofilaments, respectively. The nomenclature of these tumors,
      particularly those of the epithelial type, remains controversial. For some tumor
      types, such as those of the anterior pituitary, thyroid, and parathyroid glands,
      the standard terminology is preferable to the terms neuroendocrine tumor or
      neuroendocrine carcinoma. The use of the term carcinoid, however, has become
      increasingly more inappropriate to describe the full range of neuroendocrine
      neoplasms of low to intermediate malignant potential. It is critical to convey in
      diagnostic teminology both the tumor type and its malignant potential. Diagnostic
      terms using neuroendocrine or endocrine together with information on grading and
      hormonal activity provide an optimal approach for the classification of these
      tumors. Additional studies, including gene expression profiling, will be critical
      for further advancing our understanding of the pathobiology and
      interrelationships of these neoplasms.

PMID- 11993691
TI  - Neuroendocrine tumors of the thyroid gland.
AB  - The neuroendocrine lesions of the thyroid are few in number and include C-cell
      lesions (C-cell hyperplasia and medullary carcinoma), mixed C-cell and follicular
      derived tumors, paraganglioma, intrathyroidal parathyroid adenoma, and metastasis
      to the thyroid from neuroendocrine carcinoma arising elsewhere. However, some
      follicular-derived lesions of the thyroid can show trabecular and nesting growth
      patterns characteristic of neuroendocrine tumors. These lesions should also be
      included in the differential diagnosis of primary and secondary neuroendocrine
      tumors of the thyroid.

PMID- 11993692
TI  - Merkel cell carcinoma (neuroendocrine carcinoma of the skin).
AB  - We review the literature on Merkel cell carcinoma (MCC; primary neuroendocrine
      carcinoma of the skin) and add 36 cases to the over 800 already described in the
      literature. Though generally considered a tumor of the elderly, MCC can also
      occur in young patients. Microscopically, there are dermal proliferations of
      small cells possessing nuclei with finely dispersed chromatin. The occasional
      presence of squamous or eccrine differentiation suggests a pluripotential stem
      cell origin. Immunohistochemistry is of great help in distinguishing these tumors
      from potential mimics such as malignant melanoma, lymphoma, or metastatic small
      cell (neuroendocrine) carcinomas. Recent chromosomal studies have enhanced our
      understanding of the biology of these tumors. Despite the high metastatic rate
      associated with Merkel cell carcinoma, spontaneous regression has been reported,
      and there have been some therapeutic successes. The high survival rate for stage
      I lesions indicates the importance of early recognition and treatment of these
      tumors.

PMID- 11993693
TI  - Gastrointestinal neuroendocrine/neuroectodermal tumors.
AB  - This article reviews the cause and clinical and pathologic features of
      gastrointestinal carcinoid tumors and small cell carcinomas. Their pathogenesis
      and molecular features are reviewed. Tumor arrays within a given site, as in the
      stomach, are compared with one another to highlight their histologic features and
      differing biologies. General treatment guidelines are also provided.

PMID- 11993694
TI  - Neuroendocrine tumors of the genital tract.
AB  - Neuroendocrine tumors are more common in the female than male genital tract; most
      are uterine small cell carcinomas or ovarian carcinoids. Primary ovarian
      carcinoids are divided into insular, trabecular, strumal, and mucinous types;
      most are benign. Carcinoids metastatic to the ovary are more aggressive; most
      arise in the gastrointestinal tract. Scattered neuroendocrine cells are seen in a
      variety of ovarian surface epithelial tumors; sporadic mucinous cystic tumors
      with neuroendocrine cells have been associated with Zollinger-Ellison syndrome.
      Frank neuroendocrine carcinomas in the ovary include small cell carcinoma and
      large cell neuroendocrine carcinoma, each with a poor prognosis and often
      associated with a conventional surface epithelial tumor Such carcinomas also
      occur in the endometrium and cervix. Uterine carcinoids are rare if strict
      criteria are applied. Small cell neuroendocrine carcinomas also occur rarely in
      the vagina and vulva. Most male genital tract neuroendocrine tumors are prostatic
      small cell carcinomas or testicular carcinoids. Extragonadal carcinoids of the
      male genital tract are rare. Testicular carcinoids should be distinguishedfrom
      metastatic tumors. It is important to distinguish prostatic small cell carcinoma
      from poorly differentiated adenocarcinoma with small cells. Small cell
      neuroendocrine carcinomas also occur rarely in the scrotum, penis, and penile
      urethra.

PMID- 11993695
TI  - Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive
      protein assay as a risk marker.
AB  - C-reactive protein (CRP) is a prototypic marker of inflammation. Numerous
      prospective studies in healthy volunteers have confirmed that high-sensitivity
      CRP (hsCRP) predicts cardiovascular events (CVEs), and hsCRP seems additive to an
      elevated total cholesterol level and a total/high-density lipoprotein cholesterol
      ratio in men and women in predicting risk. In smokers and people with metabolic
      syndrome, hsCRP levels are elevated; in elderly people, there seems to be a
      relationship between hsCRP and CVEs and mortality. Several properties of CRP make
      it proatherogenic; however; pending further studies, it should be considered as a
      risk marker. In people with acute coronary syndromes, hsCRP measurement may be
      valuable. Elevated levels in the highest quantile seem to predict greater
      mortality and poorer prognosis in patients with unstable angina and myocardial
      infarction (MI). While hsCRP is a strong independent predictor of risk of future
      MI, stroke, peripheral arterial disease, and vascular death, the validity of
      hsCRP as a risk marker needs to be assessed in all populations. Weight loss,
      statin drugs, aspirin, and high-dose alpha tocopherol therapy could affect hsCRP.
      It has its greatest validity as an adjunctive measure in the primary prevention
      of cardiovascular disease.

PMID- 11993696
TI  - The perspective of a plaintiff's attorney in dissembling the art of medicine as
      it relates to the interpretation and management of cervical smears.

PMID- 11993697
TI  - Narrative interpretations for clinical laboratory evaluations: an overview.
AB  - As the clinical laboratory test menu has significantly expanded in volume and
      complexity, there is a rapidly growing need by clinicians for narrative
      interpretations of complex studies that resemble those provided in anatomic
      pathology and radiology. In this report, the impact of advice on laboratory test
      selection and interpretation is presented with regard to providing adequate
      quality of care, reducing medical error, and reducing the cost for health care.
      In addition, past and current attempts to address the physician's need for advice
      on laboratory test selection and interpretation are also described. These include
      curbside consultations, intelligent laboratory information systems, and medical
      information from the Internet. Each is presented with examples from the
      literature and with its advantages and disadvantages for practicing clinicians
      confronting large, expensive test menus and the results of esoteric assays.

PMID- 11993698
TI  - Regulations regarding reflexive testing and narrative interpretations in
      laboratory medicine.
AB  - The use of reflexive test selection and patient-specific narrative
      interpretations in laboratory medicine is associated with a host of compliance
      issues and government regulations. Reflexive testing is associated with many
      advantages for patients and their physicians, but if not adequately organized it
      has the potential for inefficient test ordering and abuse by physicians and
      laboratories. Patient-specific narrative interpretations in laboratory medicine,
      much more than fixed comments generated by a computer with a specific test
      result, also provide clinical and financial benefit when done effectively.
      Regulations exist to ensure that the physician-provided information has clinical
      value. This report describes the compliance and billing regulations regarding
      reflex testing and narrative interpretations. The codes used for narrative
      interpretations in laboratory medicine are also presented, as well as the use of
      those codes to obtain payment for the interpretation provided.

PMID- 11993699
TI  - The generation of narrative interpretations in laboratory medicine: a description
      of service-specific sign-out rounds.
AB  - The logistical details for organizing effective interpretive rounds in a
      laboratory medicine subspecialty must be carefully established so that expert
      opinions are provided in a timely fashion in a patient-specific report, rather
      than as a collection of fixed comments associated with a particular laboratory
      result generated by a computer This report describes the test batteries for
      interpretations, the billing for interpretations, clinical examples of
      interpretations, and interpretations for which billing is not typically performed
      in several clinical or laboratory areas in our institution. These include
      coagulation disorders, hemoglobin and anemia evaluations, autoimmune disorders,
      serum protein analysis, toxicology, molecular diagnostics, and transfusion
      medicine. The information in this report should provide sufficient detail to
      allow development of interpretive services with successful billing for the areas
      in laboratory medicine described.

PMID- 11993700
TI  - Diagnostic decision-making in anatomic pathology.
AB  - In diagnostic pathology, decision-making skills are used to match the facts of a
      particular case to a diagnostic category. Ideally the diagnosis is established
      with "beyond a reasonable doubt" certainty, but substantial uncertainty orfrank
      diagnostic error can afflict the diagnostic process for a variety of reasons.
      Many of these diagnostic problems are explained by failures of decision-making.
      Unfortunately, it appears that substantial components of decision-making are too
      poorly understood to study or improve. For example, "instant pattern
      recognition," use of implicit knowledge, and use of creativity represent areas
      where discussion may not be helpful. In contrast, rule-based problem-solving is
      sufficiently well understood that the members of an almost purely cognitive
      specialty might be prompted to ask, what do we know about what we do when we
      problem-solve? This article reviews some of the more intriguing aspects of
      decision-making in the hope of stimulating interest in the topic among
      pathologists.

PMID- 11993701
TI  - Error in anatomic pathology.
AB  - Error in anatomic pathology is a topic that is currently making the difficult
      transition from a problem peculiar to a subset of poorly trained or otherwise
      inadequate pathologists to a problem shared by the specialty of pathology. This
      transition will involve a number of difficult steps, including sorting error from
      both inherent diagnostic uncertainty andfrom variations in practice patterns from
      which no evidence-based best practice has emerged. Identification of error will
      require scientifically valid diagnostic gold standards, and in those areas of
      diagnosis without such a standard, the identification of and response to error
      will continue to be heavily influenced by hindsight bias and subjective opinion.
      The pathologist, like other physicians, has limited options to "make things
      right" following a significant error The silver lining is that many errors have
      the potential to prompt changes that will prevent future patient harm.
      Unfortunately, a dysfunctional legal system that values punishment and transfer
      of assets over future improvements in health care has wrung much of the positive
      potential out of error, leaving only the damaged patient and damaged pathologist.

PMID- 11993702
TI  - Applications of meta-analysis in pathology practice.
AB  - Meta-analysis is the structured and systematic integration of information from
      different studies of a given problem. It has been widely used to integrate
      findings of randomized controlled trials (RCTs) investigating the efficacy of
      therapeutic interventions, but its use in pathology has lagged behind its use in
      clinical medicine. The purpose of this review is to present pathologists with the
      necessary background for reading and evaluating published reports of
      metaanalyses. The concepts and methods of meta-analyses of RCTs are presented,
      followed by a discussion of how these concepts and methods potentially can be
      applied to studies of diagnostic test accuracy. Three differences between RCTs
      and studies of diagnostic test accuracy are identified, and 4 possible obstacles
      to the use of meta-analysis in pathology are discussed. Despite these specific
      difficulties in the meta-analysis of diagnostic test data, meta-analysis can (and
      should) be used to produce valid summary estimates of the diagnostic accuracy of
      laboratory tests across all available studies.

PMID- 11993703
TI  - Classification in anatomic pathology.
AB  - Classification is the activity that allows pathologists to arrange the
      bewildering morphologic manifestations of disease into comprehensible order
      Ideally, our precise diagnoses would each be based on some timeless biological
      law of nature, and these diagnoses would group together patients with identical
      clinical manifestations and responses to therapy. However, in spite of the
      amazing success of pathology classification, it is apparent to everyone that
      diagnostic disagreements are common, and that patients who exactly fit into a
      diagnostic category often have markedly different disease courses and responses
      to therapy. At this time, it is unclear how quickly the potential of genomic
      medicine will be translated into revolutionary changes in pathology
      classification. However, it is clear that the rules of classification are part of
      the foundation of diagnostic pathology and that there is a high likelihood that
      pathology classification will undergo substantial changes in the next few years.
      This article reviews the topic of classification for pathologists who will
      practice during these interesting times.

PMID- 11993704
TI  - Neuroendocrine neoplasms of the lung.
AB  - Neuroendocrine tumors of the lung continue to be difficult nosologic and
      diagnostic problems, centering on the time-honored terms of "carcinoid,"
      "atypical carcinoid," and "small cell carcinoma." Problems that are encountered
      in the classification of such neoplasms revolve around the differing criteria
      that have been advanced for their definition and variable application of such
      criteria in common practice. This review considers the epithelial and
      nonepithelial lesions of the lung that may demonstrate neuroendocrine and
      neuroectodermal differentiation. A proposal is made for a simplified system of
      classifying the epithelial tumors, dividing them into 3 grades with appended
      descriptive modifiers.

PMID- 11993705
TI  - Atherosclerosis: a cancer of the blood vessels?
AB  - A series of molecular pathways have in common a significant role in the
      pathogenesis and progression of atherosclerosis and cancer. Shared mechanisms
      implicated for both diseases include oxidative stress and the cellular damage
      that results from it, toxic metabolites produced by cigarette smoking, and
      increased dietary fat intake. Atherosclerosis may begin when an injury or
      infection mutates or transforms a single arterial smooth muscle cell in the
      progenitor of a proliferative clone, similar to the most widely held
      carcinogenesis theory. Cell proliferation regulatory pathways have been
      associated with plaque progression, stenosis, and restenosis after angioplasty
      and with cancer progression. Alterations in cell adhesion molecules have been
      linked to plaque formation and thrombosis and to tumor invasion and metastasis.
      Altered expression of proteases associated with thrombolysis has been implicated
      in atherosclerotic plaque expansion and hemorrhage and in the invasion and
      metastasis of malignant neoplasms. Ligand-growth factor receptor interactions
      have been associated with early atherosclerotic lesions and with cancer
      development and spread. Nuclear transcription factors have been associated with
      progression of both diseases. Angiogenesis modulators have been linked to plaque
      expansion and restenosis of atherosclerotic lesions and to local and metastatic
      tumor expansion.

PMID- 11993706
TI  - Determination of size in invasive breast carcinoma: pathologic considerations and
      clinical implications.
AB  - The widespread use of mammography has made the detection of increasingly small,
      often impalpable, invasive breast carcinomas possible. An enhanced understanding
      of morphological factors, among the foremost of which is size of invasive
      component of carcinoma, is changing the management of breast cancer To the
      uninitiated, the determination of size of invasive component is seemingly simple
      but in practical terms is complicated by a number of ambiguous issues. Practical
      guidelines for the assessment of size of invasive carcinoma are proposed.

PMID- 11993707
TI  - The histologic spectrum of apocrine lesions of the breast.
AB  - Apocrine proliferations most often are metaplasia as a component offibrocystic
      change. However, the appearance of apocrine metaplasia within various breast
      lesions, such as papillomas, ductal adenomas, and sclerosing adenosis, may
      complicate their diagnosis. Distinguishing benign from malignant apocrine
      proliferations can be problematic owing to the nuclear characteristics of
      apocrine cells. In this article, we characterize the spectrum of apocrine
      proliferations in the breast ranging from benign to malignant and attempt to
      clarify the difficult lesions that are intermediate between hyperplasia and
      ductal carcinoma in situ.

PMID- 11993708
TI  - Quantifying mammary duct carcinoma in situ: a wild-goose chase?
AB  - Duct carcinoma in situ (DCIS) is a malignant neoplasm of the breast that is
      limited to the glandular component. The introduction of mammographic screening
      allows for earlier detection of carcinoma, at the stage of DCIS, before it
      invades the surrounding stroma. Although DCIS has been studied extensively, its
      quantification remains a dilemma. Several methods for measuring DCIS exist,
      including clinical measurement, radiographic assessment, and gross pathologic
      assessment. Other methods have been employedfor this purpose, such as counting
      the number of tissue sections involved, direct measuring of DCIS from glass
      slides, and even counting the number of ducts involved. Furthermore, there is no
      consensus for assessing adequacy of margins. The myriad of techniques for
      quantifying DCIS has profound implications for treatment and for prognostic
      evaluation. The inherent difficulties in quantifying DCIS are multifactorial, and
      the need to establish a standardized approach for reporting the extent of DCIS by
      correlating radiographic, clinical, gross, and histologic findings is imperative.

PMID- 11993709
TI  - Fine-needle aspiration cytology of in situ epithelial cell proliferation in the
      breast.
AB  - The cytomorphologic features of in situ proliferative breast lesions encompass a
      spectrum ranging from those of a simple benign lesion to atypical to those
      indistinguishable from invasive carcinoma. In the majority of cases, however, the
      features are distinctive and easily recognized, and allow accurate categorization
      of these lesions on the basis of fine-needle aspiration biopsy. As in tissue
      sections, recognition of these lesions is based on both cytologic and
      architectural characteristics. Familiarity with these features is necessary for
      the appropriate management of cases of in situ proliferative breast disease.
      Among the proliferative breast lesions, those with no associated atypia represent
      the majority of cases and can be clinically monitored without the needfor
      confirmation biopsy. In lesions with associated atypia, however, the
      cytomorphologic features may overlap with those of low-grade carcinoma, and thus
      tissue biopsy is required for a definitive diagnosis. The value of ancillary
      studies to further categorize these lesions is limited.

PMID- 11993710
TI  - Current issues in breast cytopathology.
AB  - This article explores 3 aspects of breast diagnosis that are currently under
      investigation and about which our thinking has recently undergone considerable
      reshaping. The trend toward more frequent evaluation of clinically subtle lesions
      has suggested that it might be necessary to understand thefine-needle aspiration
      (FNA) presentation of proliferative breast disease. Efforts to do so, as well as
      our suggestions for additional studies and their potential limitations open this
      discussion. Following this section, the increasingly useful method of
      intraoperative cytology for evaluation of resected breast masses is considered in
      detail. In the final section, optimization of nonoperative sampling by
      combination of mammography, ultrasonography, fine-needle aspiration, and core
      biopsy is discussed and illustrated.

PMID- 11993711
TI  - Prognostic information from fine-needle aspiration biopsy of breast carcinoma.
AB  - Fine-needle aspiration of the breast is one of the most common procedures
      performed on patients with a palpable breast mass. The pathologist needs to be
      aware of the diagnostic and prognostic parameters that must be included in the
      cytopathology report of breast carcinomas. These fundamental parameters include
      tumor type, nuclear grade of the carcinoma, and hormone receptor status.

PMID- 11993712
TI  - Assessment of prognostic factors in breast fine-needle aspirates.
AB  - Because of the enhanced effects of new chemotherapeutic agents on the survival of
      patients with breast cancer, there has been increased interest in the use of
      prognostic factors. In the last several years, the literature has been saturated
      with new information about the prognostic/predictive value of traditional factors
      as well as the newly recognized biomarkers. Controversy, however, remains about
      the validity of each of the factors as independent prognostic indicators. The
      standard prognostic factors, recognized by the National Cancer Institute in 1990,
      include lymph node status, tumor size, nuclear grade, steroid receptor content,
      tumor type, and cellular proliferation rate. It is also recommended that for
      patients who undergo preoperative chemotherapy or radiotherapy, breast fine
      needle aspirates can be used to provide prognostic information. This article is
      designed to discuss the traditional and also the newly recognized factors, such
      as DNA ploidy and proliferation rate, HER-2/neu oncogene, and tumor suppressor
      gene p53, in breast fine-needle aspirates and their clinical application in
      breast cancer management. An overview of the proposed guidelines developed by the
      National Cancer Institute is also presented.

PMID- 11993713
TI  - Bronchoscopic needle aspiration biopsy.
AB  - Bronchoscopic needle aspiration biopsy, which encompasses transbronchial needle
      aspiration, transtracheal needle aspiration, and endobronchial needle aspiration,
      is a minimally invasive technique used to diagnose mediastinal and pulmonary
      masses and to stage lung cancer patients with mediastinal lymphadenopathy. Since
      it is safe, accurate, and potentially cost-efficient, its use may increase in the
      coming years. It is important that pathologists who examine cytology specimens
      understand this procedure, its limitations, and ways that it may be optimized.

PMID- 11993714
TI  - Antidepressants, eicosanoids and the prevention and treatment of cancer. A
      review.
AB  - Among the mechanisms of carcinogenesis are oncogene synthesis and expression,
      upregulation of cyclooxygenase, accelerated cell replication, failed apoptosis,
      viral activation, disruption of signaling pathways, autoimmunity,
      immunosuppression, angiogenesis and metastasis. All fall within the orbit of
      eicosanoids and the enzymes that synthesize them. Antidepressants may be of
      benefit in the prevention and treatment of cancer, as they inhibit the synthesis,
      antagonize the actions and accelerate the degradation of such eicosanoids as
      prostaglandins and thromboxanes.

PMID- 11993715
TI  - Study of the paraoxonase and platelet-activating factor acetylhydrolase
      activities with aging.
AB  - The purpose of this study was to investigate, with aging, the activity of two
      enzymes associated to HDL and responsible for its anti-atherogenic activity;
      paraoxonase (PON1) and platelet-activating factor acetylhydrolase (PAF-AH).
      Ninety-five subjects aged between 26 and 77 years were recruited for the study.
      The prevalence of phenotype A, AB, and B in our subjects group was 69.47,21.05
      and 9.47% respectively. Plasma as well as HDL paraoxonase activity decreased
      significantly with aging (r =-0.218, P < 0.039) and (r = -0.280, P < 0.006)
      respectively. PAF-AH activity was unchanged with aging however, we noted a
      negative correlation between PAF-AH and PON1 activity in HDL (r = -0.243, P <
      0.02) and in LDL vs HDL (r =-0.462, P < 0.001).

PMID- 11993716
TI  - Regulation of prostaglandin biosynthesis in dispersed choriodecidual cells in
      culture.
AB  - We have evaluated the prostaglandin (PG) production and PG biosynthetic gene
      expression in a choriodecidual dispersed cell culture system. Cells dispersed
      from human choriodecidual membranes by dispase and trypsin digestion were
      evaluated after 1,3,5 and 7 days of culture for basal and tumour necrosis factor
      alpha (F-alpha) stimulated PGE2 production. The highest rates of production (P <
      0.05) were obtained with cells treated after 3 days of culture, (3.7 +/- 1) x
      10(2) pg PGE2 per 16 h per microg total cellular protein (mean +/- SEM), which
      was 3.9 times basal rate after 3 days culture. In choriodecidual cells treated
      after 3 days in culture, expression of prostaglandin endoperoxide H synthase-2
      (PGHS-2) mRNAwas similarly responsive toTNF-alpha (3.9 times basal within 3 h of
      30 ng/ml TNF-alpha) while there was little effect on PGHS-1 or cytosolic
      phospholipase A2 expression. Hence, the dispersed choriodecidual cell culture
      system described retainsTNF-alpha responsive PG biosynthetic capacity which is at
      least in part upregulated via increased expression of PGHS-2 mRNA.

PMID- 11993717
TI  - Pharmacology of functional endogenous IP prostanoid receptors in NCB-20 cells:
      comparison with binding data from human platelets.
AB  - The objective of these studies was to characterize the effects of a broad range
      of prostanoid agonists upon the stimulation of cAMP production in National Cancer
      Bank (NCB-20; mouse neuroblastoma/hamster brain hybridoma) cells. The
      pharmacology of these functional responses in NCB-20 cells was compared with that
      of the classic endogenous IP receptor present on human platelets using [3H]
      iloprost binding techniques. In both assay systems, agonists from the IP
      prostanoid class exhibited the highest affinities and functional potencies.
      Specific prostanoids exhibited the following rank order of potency (EC50 +/- SEM)
      in stimulating cAMP production in the NCB-20 cells: carbaprostacyclin (4.3 +/-
      0.9 nM) = PGI2 (6.6 +/-1.5 nM) > iloprost (75+/-13 nM) > 11-deoxy PGE, (378+/-138
      nM) > misoprostol (1,243+/-48) > PGE2 (3020+/-700 nM) > ZK-118182 (7265+/-455
      nM). Iloprost wasthe most potent compound in the human platelet binding assay
      while prostanoidsfromthe DPand EP receptor classes showed modest affinity. These
      studies provide functional and binding information for a broad range of both
      natural and synthetic prostanoid receptor ligands at the endogenous IP receptor
      in two different cell types.

PMID- 11993718
TI  - Nitric oxide in CsA-induced hypertension: role of beta-adrenoceptor antagonist
      and thromboxane A2.
AB  - Cyclosporine A (CsA) is an immunosuppressive agent, which also causes
      hypertension. The effect of CsA on vascular responses was determined in Sprague
      Dawley rats and rat aortic rings. Male rats weighing 250-300 g were given either
      CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal (ip) injection for
      7 days. CsA administration produced a 42% increase (P < 0.001) in mean arterial
      pressure (MAP) which reached a plateau after 3 days. The level of both
      nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), decreased by 50% (P
      < 0.001), but the level of thromboxane A2 (TBXA2) increased by 75% (P < 0.001),
      in the urine. When 10(-9) M of CsAwas added acutely to intact aortic rings from
      untreated rats, NO2/NO3 production decreased by 83% (P < 0.011), but TBXA2
      production increased by 86% (P < 0.001). The effects of CsA were reversed both in
      vivo and in vitro by pretreatment with propranolol (15 mg/kg/day ip), beta
      adrenoceptor antagonist. There were no changes in MAP and tension in rats treated
      with prop alone. In addition, in aorta of rats that were treated with CsA ip for
      7 days, CsA significantly activated protein kinase C (PKC) translocation. This
      suggests that PKC mediate, in part, CsA-induced hypertension. In summary, CsA
      inhibits endothelial NO formation, activate PKC, and increaseTBXA2 production,
      with resulting increase in MAP, and this changes can be overcome by pretreatment
      with propranolol.

PMID- 11993719
TI  - Attenuation of oxalate-induced nephrotoxicity by eicosapentaenoate-lipoate (EPA
      LA) derivative in experimental rat model.
AB  - Hyperoxaluria is one of the major risk factors for the formation of urinary
      calcium oxalate stones. Calcium oxalate crystals and their deposition have been
      implicated in inducing renal tubular damage. Lipoic acid (LA) and
      eicosapentaenoic acid (EPA) have been shown to ameliorate the changes associated
      with hyperoxaluria. This prompted us to investigate the nephroprotectant role of
      EPA-LA, a new derivative, in vivo in hyperoxaluric rats. Elevation in the levels
      of calcium, oxalate and phosphorus, the stone-forming constituents, were observed
      in calculogenic rats as a manifestation of crystal deposition. Tubular damage to
      the renal tissue was assessed byassaying the excretion of marker enzymes in the
      urine. Damage to the tubules was indicated by increased excretion of alkaline
      phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (gamma
      GT), beta-Glucuronidase (beta-GLU) and N-Acetyl beta-D glucosaminidase (NAG).
      Fibrinolytic activity was found to be reduced. Administration of EPA, LA and EPA
      LA reduced the tubular damage and decreased the markers of crystal deposition
      markedly, which was substantiated by the reduction in weight of bladder stone
      formed. Our results highlight that EPA-LA is the most effective drug in
      inhibiting stone formation and mitigating renal damage caused by oxalate
      toxicity, thus confirming it as a nephroprotectant. Further work in this
      direction is warranted to establish the therapeutic effectiveness of this new
      derivative.

PMID- 11993720
TI  - Determination of 9alpha, 11beta prostaglandin F2 in human urine. combination of
      solid-phase extraction and radioimmunoassay.
AB  - This paper describes a new iodine-125 radioimmunoassay of 9alpha ,11beta-PGF2,
      and its use for the determination of urinary 9alpha,11beta-prostaglandin F2 after
      a selective one-step solid-phase extraction. The newly reported immunoassay is
      based on the use of 125I-tyrosyl methyl ester derivative of 9alpha,11beta-PGF2
      and specific polyclonal antibody raised in rabbits. The assay detected as lowas
      0.85 pg/tube 9alpha,11beta-PGF2, and the antibodyshowed lessthan 0.01 cross
      reaction with PGF-ring metabolites (e.g., 8-iso-PGF2alpha, PGF2alpha 2,3-dinor-6
      keto-PGF1alpha, and 5 more PGF-ring compounds). Both the intra-assay, and inter
      assay CVs were lessthan 20% for internal controls containing low, medium and high
      concentrations of 9alpha,11beta-PGF2. Immuno-HPLC analysis showed a very low
      ratio of specific immunoreactivity in both non-extracted urine (6.5%), and in
      urine extracted on C18-silicacartridge (14.8%). By contrast, approximately 80%
      specific immunoreactivity could be achieved by using C2-silicaas the sorbent,
      acetonitrile: water (15:85, v/v) as wash solvent, and ethyl acetate as eluent of
      9alpha,11beta-PGF2. This extraction procedure enabled a reasonably high
      extraction efficiency of 80.4 +/- 0.855 (mean +/- SEM, n=82), as determined by 3H
      9alpha,11beta-PGF2. The new SPE/RIA method was applied for the determination of
      urinary 9alpha,11beta-PGF2 values in 50 healthy human volunteers. For the
      concentration and for the excretion rate 37.52 +/- 4.61 pg/ml (mean +/- SEM), and
      3.50 + 0.35 ng/mmol creatinine (mean +/- SEM), respectively, was measured. The
      specificity of the SPE/RIA method was supported by the observed 69% decrease in
      9alpha, 11beta-PGF2 excretion rate after acetylsalicylic acid treatment. The
      effect of nicotinic acid, a PGD2-stimulatory agent, was monitored by the urinary
      excretion of 9alpha ,11beta-PGF2 in 6 patients, by using the new SPE/RIA method.
      In patients responding with flushing symptoms nicotinic acid induced an increase
      of the urinary excretion of 9alpha,11beta-PGF2 in the range between 11% and 187%.
      In summary, the combination of the newly developed specific [125I]
      radioimmunoassay with solid-phase extraction on C2-silica cartridges enables the
      specific, sensitive, and reliable determination of 9alpha,11beta-PGF2 in human
      urine without the need for further laborious chromatographic purification before
      radioimmunoassay.

PMID- 11993721
TI  - Flavonoids differentially inhibit guinea pig epidermal cytosolic phospholipase
      A2.
AB  - Cytosolic phospholipase A2 (cPLA2) is believed to involve the regulation of
      essential cellular processes. Like other cell types, epidermal cPLA2 may
      participate in various metabolic processes including eicosanoid generation. In
      this investigation, we demonstrated the presence of cPLA2 in guinea pig
      epidermis. The epidermal cPLA2 is Ca2+-dependent, active at micromolar
      concentration of Ca2+ and resistant to disulfide-reducing agents. Furthermore, it
      is inhibited by methyl arachidonyl fluorophosphonate (MAFP), a selective
      inhibitor of cPLA2, while 12-epi-scalardial (a sPLA2 inhibitor) did not cause
      inhibition. A test of several flavonoids revealed that quercetin (flavonol)
      weakly inhibited cPLA2, while flavanone had negligible inhibitory activity. In
      contrast, amentoflavone and ginkgetin (biflavones) markedly inhibited cPLA2
      activity in the epidermis. These results underscore that different flavonoids do
      vary in their capability to exert differential effects on arachidonate metabolism
      in the skin via modulation of epidermal cPLA2 activity.

PMID- 11993722
TI  - Differential mRNA expression of prostaglandin receptor subtypes in macrophage
      activation.
AB  - Assessing the regulation of macrophage receptors for prostaglandin (PGE2) is
      essential to understanding the control which that potent lipid mediator has in
      modulating macrophage activities. The purpose of this study was to assess the
      differential mRNA expression of PGE2 receptor subtypes (EP) during macrophage
      exposure to activating and transducing agents. RAW 264.7 macrophages
      constitutively expressed mRNA for EP2,EP3 and EP4 receptor subtypes. Messenger
      RNA for EP4 was expressed at a much higher level when compared to EP2 in
      unstimulated macrophages as assessed by kinetic quantitative RT-PCR. When
      macrophages were stimulated with LPS, EP2 m RNA levels were 12-fold higher when
      compared to unstimulated macrophages, while EP4 m RNA remained unchanged.
      Conversely, mRNA levels of both EP2 and EP4 receptors were lower after
      macrophages were treated with IFN-gamma. Messenger RNA levels of both receptors
      were lower in macrophages after treatment with PGE2 or dibutyryl (db) cAMP
      Addition of the PKA inhibitor H89 reversed the effects of PGE2 and dbcAMP to
      varying degrees. Proteosome and p38 MAP kinase inhibitors blocked the LPS
      stimulated increase in EP2 mRNA levels. Those inhibitors had no effect on EP4
      mRNA.Thus, activating agents such as LPS and IFN-gamma may differentially
      regulate mRNAfor PGE2 receptor types in macrophages but the ligand and its
      associated signal transducing factors probably have similar regulatory effects.

PMID- 11993723
TI  - Uptake and metabolic conversion of saturated and unsaturated fatty acids in Hep2
      human larynx tumor cells.
AB  - Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was
      carried out. The cells were incubated with either a saturated (palmitic) or a
      polyunsaturated (linoleic, alpha-linolenic and eicosatrienoic (n-6)) radioactive
      fatty acid (0.66 pM, 24 h). The best incorporation capacity was observed in the
      linoleic acid followed by alpha-linolenic, palmitic and eicosatrienoic acids. All
      fatty acids tested were anabolized to higher derivatives within their own family.
      Palmitic acid was primarily monodesaturated rather than elongated, proving to
      have a very active A9 desaturase activity. With respect to polyunsaturated acid
      metabolism, the conversion of alpha-linolenic acid to higher homologs, although
      better than linoleic acid, occurred far less efficiently than that observed in
      other non-highly undifferentiated human tumor cells. This impairment in higher
      polyunsaturated fatty acid biosynthesis, reflected in the low levels of
      arachidonic acid in the fatty acid composition, would not reside in the A5
      desaturation step since Hep2 cells can readily convert eicosatrienoic acid into
      arachidonic acid. Considering the potential regulatory role of specific
      polyunsaturated fatty acids in the cell proliferative control, the knowledge of
      the metabolism of fatty acids in this human tumor cell would be important for
      designing future experiments in order to clarify the mechanism involved in
      balance, proliferation and cell death.

PMID- 11993724
TI  - Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with
      rheumatoid arthritis.
AB  - Thromboxane and leukotrienes have been implicated in inflammation. However, the
      production level of these eicosanoids in patients with rheumatoid arthritis is
      still unclarified. In the present study, endogenous synthesis of thromboxane and
      cysteinyl leukotrienes in patients was investigated. The production of
      eicosanoids in patients is assessed by measuring stable urinary metabolites,11
      dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion
      monitoring and liquid chromatography/tandem mass spectrometry. The level of
      urinary thromboxane in patients was significantly higher than that in healthy
      volunteers (P < 0.05). Furthermore, we investigated the effects of administered
      drugs on the production of these eicosanoids. The urinary thromboxane level of
      the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of
      healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group
      receiving NSAID alone was similar to that in healthy volunteers, and the group
      receiving steroid alone showed slightly lower thromboxane levels than the
      untreated group. On the other hand, the leukotriene E4 level in patients (280 +/-
      360 pg/mg creatinine) was also significantly higher than that in healthy
      volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group
      receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene
      levels than not only healthy volunteers but also other medicated groups. These
      findings demonstrated that endogenous thromboxane and leukotriene production in
      patients with rheumatoid arthritis are enhanced, and the effects of medication on
      the production of these eicosanoids differed in thromboxane and leukotriene E4.

PMID- 11993725
TI  - Intractable epilepsy in adults.
AB  - Drug-resistant or "intractable" epilepsy presents a major challenge for
      physicians, epilepsy associations and researchers. Dr. Leppik discusses the
      evaluation of patients who may be intractable, the nature of intractable epilepsy
      and the factors which contribute to intractability.

PMID- 11993726
TI  - Why are complex partial seizures intractable?
AB  - Dr. Burnham argues that data from animal studies--and especially kindling studies
      -can provide insights into why complex seizures are so common and drug resistant.

PMID- 11993727
TI  - Pathophysiology of infantile spasms.
AB  - Infantile spasms--seen in West's Syndrome--are often associated with cortical
      abnormalities. The spasms themselves, however, appear to be generated
      subcortically. Dr. Chugani reviews the clinical data related to the
      pathophysiology of infantile spasms and proposes a hypothesis which involves both
      cortical and subcortical mechanisms.

PMID- 11993728
TI  - A window on the physiopathogenesis of seizures in patients with cortical
      dysplasia.
AB  - Cortical dysplasia is found in many cases of intractable epilepsy. Dr. Avoli
      reports that dysplastic cortex--removed from human brains during seizure surgery-
      shows abnormal excitability in vitro.

PMID- 11993729
TI  - Psychiatric aspects of intractable epilepsy.
AB  - Dr. Blumer argues that intractable temporal lobe epilepsy is often accompanied by
      a psychiatric syndrome, which he calls "interictal dysphoric disorder".
      Interictal dysphoric disorder is surprisingly responsive to antidepressant
      medications, although it is seldom diagnosed or treated.

PMID- 11993730
TI  - Neural growth, neural damage and neurotrophins in the kindling model of epilepsy.
AB  - Do seizures change the brain? Studies on the kindling model--a widely used animal
      model of epilepsy--suggest that they do. Dr. Racine, one of the pioneers in the
      kindling field, describes the basic phenomena of kindling, and discusses the
      possible roles of cell growth and cell death in this model.

PMID- 11993731
TI  - Effects of uncontrolled seizures. Neural changes in animal models.
AB  - Doctors Stafstrom and Holmes have spent several years studying the brain damage
      and behavioral deficits caused by repeated seizures or status epilepticus. They
      discuss possible mechanisms and the effects of age.

PMID- 11993732
TI  - Drug therapy for complex partial seizures.
AB  - Complex partial seizures present a major challenge for medical management. Dr.
      Bruni reviews the available drugs, including the novel anticonvulsants which have
      recently become available.

PMID- 11993733
TI  - The Landau-Kleffner syndrome.
AB  - Landau-Kleffner Syndrome is a rare childhood disorder which involves seizures and
      acquired aphasia. Anticonvulsants, or the passage of time, may control the
      seizures, but speech recovery is variable, and the aphasia may persist.

PMID- 11993734
TI  - Neuroprotective strategies in epilepsy.
AB  - Dr. Carlen reviews the evidence that seizures may cause cell death and discusses
      possible strategies for preventing seizure-induced brain damage.

PMID- 11993735
TI  - The ketogenic diet.
AB  - One of the most significant trends in therapy has been the renewed popularity of
      the ketogenic diet. Dr. Vining discusses the history of the diet, its possible
      mechanisms of action and its clinical efficacy.

PMID- 11993736
TI  - Vagal stimulation for intractable seizures.
AB  - Vagal stimulation has recently been approved for use in North America. Dr. Upton
      discusses the findings of a study conducted at the McMaster Medical Centre.

PMID- 11993737
TI  - Surgery for complex partial seizures.
AB  - Dr. Girvin discusses the technique of surgery for complex partial seizures, some
      of the questions and controversies related to this technique and the probability
      of a successful outcome.

PMID- 11993738
TI  - West's syndrome (infantile spasms). Clinical description and diagnosis.
AB  - West's syndrome is a serious epileptic syndrome which usually begins in the first
      year of life. It involves seizures known as "infantile spasms". Dr. Hrachovy
      describes the disorder and its symptoms.

PMID- 11993739
TI  - Drug therapy for West's syndrome.
AB  - West's syndrome resists most of the standard anticonvulsants. It may respond,
      however, to steroids or to some of the newer drugs like vigabatrin.

PMID- 11993740
TI  - Surgery for West's syndrome.
AB  - Many cases of West's syndrome are inoperable, because there is no clear epileptic
      focus. In some cases, however, there is a structural abnormality which can be
      surgically removed. Dr. Hoffman discusses his experience with surgery for
      cortical dysplasia in West's syndrome.

PMID- 11993741
TI  - Lennox-Gastaut syndrome. Clinical description and diagnosis.
AB  - The Lennox-Gastaut syndrome (LGS) is widely known as one of the most severe and
      prognostically unfavourable epileptic conditions. Its entity as a syndrome is
      based on the occurrence of certain characteristic types of seizure (particularly
      typical drop attacks and axial tonic seizures) and on EEG patterns such as the
      slow spike-wave complex and runs of rapid spikes (10-25/sec).

PMID- 11993742
TI  - Drug therapy in Lennox-Gastaut syndrome.
AB  - Like West's syndrome, Lennox-Gastaut syndrome resists most of the standard
      anticonvulsants. Dr. Farrell discusses the first- and second-line drugs which may
      be used--plus the ketogenic diet.

PMID- 11993743
TI  - Surgery in Lennox-Gastaut syndrome. Corpus callosum division for children.
AB  - A tonic or "drop" attacks--often seen in Lennox-Gastaut syndrome--are some of the
      most feared childhood seizures, since they may lead to head injuries. Corpus
      callosum division will often control atonic seizures, and other types of
      generalized seizure.

PMID- 11993744
TI  - Complex partial seizures. Clinical description and diagnosis.
AB  - A few types of epilepsy are particularly drug-resistant. These include West's
      syndrome, Lennox-Gastaut syndrome and complex partial epilepsy. Of these, complex
      partial epilepsy is by far the most common.

PMID- 11993745
TI  - Modeling the costs and outcomes of cardiovascular surgery.
AB  - Coronary artery bypass graft (CABG) operations consume more health care resources
      than any other single procedure. The objective of this study was to develop a
      computer simulation model that can be used to predict costs and patient outcomes
      of CABG surgery. The analysis is based on a systems dynamic model developed using
      STELLA software. Two sets of data from Medicare patients who underwent CABG
      operations at Methodist Hospital of Indiana were used to construct and validate
      the model. The model predictions of length of hospital stay, use of specialists
      in caring for patients, costs and postoperative functional status are reasonably
      close to actual data on patients who underwent CABG surgery. The analysis
      indicates the most important factors affecting costs and outcomes are gender,
      age, whether or not the surgery is a reoperation and whether the patient
      experiences postoperative complications. The model can be used to predict costs
      and outcomes for a patient population from a small set of preoperative
      characteristics (i.e., age, gender, DRG, whether the surgery is a reoperation,
      and the patient's operative status). A second potential use of the model is to
      answer clinical questions such as do the costs and risks of CABG operations
      outweigh the benefits for patients with certain risk factors.

PMID- 11993746
TI  - The use of simulation models for the surveillance, justification and
      understanding of tobacco control policies.
AB  - Debates over national tobacco legislation and the use of state settlement funds
      demonstrate a need for information on the effects of tobacco control policies.
      Computer simulation models that are based on empirical evidence and that account
      for the variety of influences on tobacco use can be useful tools for informing
      policy makers. They can identify the effects of different policies, convey the
      importance of policy approaches to tobacco control, and help policy planners and
      researchers to better understand policies. This paper examines the role of
      simulation models in public policy, and discusses several recent models and
      limitations of those models.

PMID- 11993747
TI  - Using simulation for AIDS policy modeling: benefits for HIV/AIDS prevention
      policy makers in Vienna, Austria.
AB  - In spite of advanced therapies and the success of additional prevention programs,
      the HIV/AIDS epidemic still remains a challenge. Our paper refers academics,
      health care managers, and policy makers to the relevance of AIDS policy
      simulators in better decision-making. By highlighting the types of decisions AIDS
      policy models can support, we demonstrate the strategic role of AIDS policy
      simulators for the efficient and effective planning of scarce resources to fight
      the epidemic. For each type of decision, we then review exemplary AIDS policy
      simulators that have helped policy makers make better decisions. Finally, we
      present the benefits of an AIDS policy simulator for HIV/AIDS prevention policy
      makers in Vienna, Austria.

PMID- 11993748
TI  - Using Monte Carlo simulation to determine combination vaccine price distributions
      for childhood diseases.
AB  - The Recommended Childhood Immunization Schedule provides guidelines that allow
      pediatricians to administer childhood vaccines in an efficient and effective
      manner. Research by vaccine manufacturers has resulted in the development of new
      vaccines that protect against a growing number of diseases. This has created a
      dilemma for how to insert such new vaccines into an already crowded immunization
      schedule, and prompted vaccine manufacturers to develop vaccine products that
      combine several individual vaccines into a single injection. Such combination
      vaccines permit new vaccines to be inserted into the immunization schedule
      without requiring children to be exposed to an unacceptable number of injections
      during a single clinic visit. Given this advantage, combination vaccines merit an
      economic premium. The purpose of this paper is to describe how Monte Carlo
      simulation can be used to assess and quantify this premium by studying four
      combination vaccines that may become available for distribution within the United
      States. Each combination vaccine is added to twelve licensed vaccine products for
      six childhood diseases (diphtheria, tetanus, pertussis, haemophilus influenzae
      type B, hepatitis B, and polio). Monte Carlo simulation with an integer
      programming model is used to determine the (maximal) inclusion price distribution
      of four combination vaccines, by randomizing the cost of an injection. The
      results of this study suggest that combination vaccines warrant price premiums
      based on the cost assigned to administering an injection, and that further
      developments and innovations in this area by vaccine manufacturers may provide
      significant economic and societal benefits.

PMID- 11993749
TI  - Random vs. nonrandom mixing in network epidemic models.
AB  - In this paper we compare random and nonrandom mixing patterns for network
      epidemic models. Several of studies have examined the impact of different mixing
      patterns using compartmental epidemic models. We extend the work on compartmental
      models to the case of network epidemic models. We define two nonrandom mixing
      patterns for a network epidemic model and investigate the impact that these
      mixing patterns have on a number of epidemic outcomes when compared to random
      mixing. We find that different mixing assumptions lead to small but statistically
      significant differences in disease prevalence, cumulative number of new
      infections, final population size, and network structure. Significant differences
      in outcomes were more likely to be observed for larger populations and longer
      time horizons. Sensitivity analysis revealed that greater differences in outcomes
      between random and nonrandom mixing were associated with a larger incremental
      mortality rate among infected individuals, a larger average number of partners,
      and a greater probability of forming new partnerships. When adjusted for the
      initial population size, differences between random and nonrandom mixing models
      were approximately constant across all population sizes considered. We also
      considered the impact that differences between mixing models might have on the
      cost effectiveness ratio for epidemic control interventions.

PMID- 11993750
TI  - Evaluating the design of a family practice healthcare clinic using discrete-event
      simulation.
AB  - With increased pressures from governmental and insurance agencies, today's
      physician devotes less time to patient care and more time to administration. To
      assist physician clinics in evaluating potential operating procedures that
      improve operating efficiencies and better satisfy patients, an object-oriented
      discrete-event simulation model has been constructed using the Visual Simulation
      Environment (VSE). The research presented herein describes a methodology for
      determining appropriate staffing and physical resources in a clinical environment
      using this simulation model. This methodology takes advantage of several
      simulation-based statistical techniques, including batch means: fractional
      factorial design: and simultaneous ranking, selection, and multiple comparisons.
      A clinic effectiveness measure is introduced that captures several objectives
      within a health care clinic, including profitability and patient satisfaction. An
      explanation of the experimental design is provided and results of the
      experimentation are presented. Based upon the experimental results, conclusions
      are drawn and recommendations are made for an appropriate staffing and facility
      size for a two physician family practice healthcare clinic.

PMID- 11993751
TI  - A decision support simulation model for the management of an elective surgery
      waiting system.
AB  - This paper describes the design of a simulation model to provide decision support
      for the scheduling of patients waiting for elective surgery in the public
      hospital system. Patients nominated for surgery by doctors are categorised by
      urgency and type of operation. The simulation model can be used as an operational
      tool to match hospital availability and patient need. It can also be used to
      report upon the performance of the system, and as a planning tool to compare the
      effectiveness of alternative policies in this multi-criteria decision
      environment.

PMID- 11993752
TI  - Simulation studies and the alignment of interests.
AB  - Chemotherapy patients are treated with cytostatic drugs. Cytostatic drugs can be
      produced if ordered or they can be produced to keep in stock. The time that
      cytostatic drugs can be kept in stock before being spoiled is limited. It is
      always possible that the patient cannot receive chemotherapy because he/she is
      not in the right condition. A simulation model is presented which allows to
      calculate for each combination of patient type and cytostatic drug type the
      effects on waiting times and costs. In practice actors will behave not as
      recommended by the simulation model. The cause of the latter is analyzed and
      solutions are proposed.

PMID- 11993753
TI  - Biological monitoring of wood dust exposure in nasal lavage by high-performance
      liquid chromatography.
AB  - A high-performance liquid chromatography (HPLC) method for biomonitoring of
      occupational wood dust exposure based on nasal lavage as a biomonitoring matrix
      was developed. Gallic acid (GA) was chosen as the indicator compound for oak dust
      exposure. From the chromatographic profile of ash dust, four peaks were chosen as
      indicator compounds. Phenolic indicator compounds were analysed by HPLC. Personal
      dust samples and corresponding nasal lavage samples were collected from 16
      workers exposed to oak dust and six to ash dust. The dust concentrations in the
      workers' breathing zone varied between 0.7 and 13.8 mg m(-3). The indicators
      revealed the nature of the wood dust inhaled. For the workers who did not use
      respirators, the correlation between the dust and corresponding indicator
      compound in their nasal lavage was significant; r2 = 0.59 (n = 12) for oak dust
      and r2 = 0.58 (n = 6) for ash dust, respectively. Further, the correlation for
      oak dust workers who used respirators was r = 0.67 (n = 4). Nasal lavage sampling
      and HPLC analysis of polyphenol indicator compounds are promising tools for
      measuring wood dust exposure. Although further validation is necessary,
      determination of the individual dose may prove invaluable in prospective
      epidemiological studies.

PMID- 11993754
TI  - A rapid and sensitive analytical method for the quantification of residues of
      endosulfan in blood.
AB  - A new sensitive analytical procedure has been developed for the determination of
      residues of endosulfan in human blood samples. The method involves the extraction
      of residues of endosulfan from blood samples by the addition of 60% sulfuric acid
      at 10 degrees C, liquid/liquid partitioning by using hexane and acetone mixture
      (9:1) and quantification by using GC-ECD. Residues of endosulfan in blood samples
      were quantified as the sum of alpha-endosulfan, beta-endosulfan, endosulfan
      sulfate and endosulfandiol. The influence of temperature during the extraction
      has been studied. Recovery experiments were conducted over the concentration
      range 1.0-50 ng ml(-1) and the relative standard deviation calculated. The method
      was found to be sufficiently sensitive to quantify the residue of total
      endosulfan up to the 1.0 ng ml(-1) level. The recovery was 92% with a calculated
      relative standard deviation of 1.96%. Conversion of endosulfan to endosulfandiol
      is found to be less than 0.5% under the defined conditions. The method was
      applied to the analysis of residue contents of endosulfan and its metabolites in
      blood samples collected from the exposed population. The data obtained has been
      confirmed by GC-MS-EI in selective ion monitoring (SIM) mode.

PMID- 11993755
TI  - Evaluation of a novel structural model to describe the endogenous release of lead
      from bone.
AB  - The aim of this paper was to assess the endogenous release of lead from bone to
      blood, in 204 exposed subjects. resuming their duties after a 10-month strike in
      a primary lead smelter in 1991. In vivo 109Cd K X-ray Fluorescence (109Cd K XRF)
      was used to measure the bone lead concentration in tibia and calcaneus in the
      smelter, in 1994 and five years later. The 1994 data were used to derive the post
      strike bone lead concentrations retrospectively from the significant association
      between bone lead and the cumulative blood lead index (CBLI). When a linear model
      was used to predict the current blood lead upon the level of lead in bone,
      structural analysis of the data produced slopes for tibia (2.0, 95% CI 1.66-2.54)
      and calcaneus (0.19, 95% CI 0.16-0.23) that were significantly higher than those
      predicted by the commonly used simple linear regression method, for tibia (0.73,
      95%, CI 0.58-0.88) and calcaneus (0.08, 95% CI 0.06-0.09). This suggests that
      more lead than previously predicted by regression is released from bone to blood.
      Furthermore, the structural analysis of the data produced an estimation of the
      contribution of the bone lead stores to the bloodstream that was more consistent
      with the 1999 epidemiological data than did the regression estimation. Moreover,
      a non-linear relationship between tibia lead and blood lead was suggested from
      the assumption checking procedures for regression. When a non-linear regression
      model was fit to the data, the method produced estimates of important parameters
      in human lead kinetics, namely the blood lead saturation constant, showing a good
      agreement with current knowledge of lead metabolism. Finally, the likelihood of a
      non-linear bone lead release seems to be supported by the recently described
      dependence of the half-life of lead in bone on age and intensity of occupational
      exposure.

PMID- 11993756
TI  - Impact of long-term exposure to mosquito coils: residual deposition and
      dissipation of D-trans-allethrin in a room.
AB  - A D-trans-allethrin-based mosquito repellent coil formulation was used
      continuously in a room for 30 d. Two different experiments were conducted and the
      deposition of residues on different surfaces of the room was determined. Studies
      were conducted continuously for a period of 30 d in a fully closed room and in
      another room kept open for 14 h per day. The residues deposited on different
      surfaces, ceiling, side walls and floor, were measured. The results showed the
      accumulation of high concentrations of allethrin on all the surfaces of the room
      when the room was in a fully closed condition. Samples collected from the ceiling
      showed residues of D-trans-allethrin of 6.34-148.63 microg m(-2) during the 30 d
      study, the side walls 4.68-170.72 microg m(-2) and the floor 20.00-184.52 microg
      m(-2) Maximum residues were observed in 30 d samples collected from the ceiling
      and floor. The residual concentrations were nearly 10 times higher in samples
      collected from the closed room. Discontinuation of the use of the mosquito
      repellent after 30 d led to a gradual decrease in the concentrations of residues
      on all the surfaces. The influence of environmental parameters on the dissipation
      of residues was also studied.

PMID- 11993757
TI  - Monitoring ammonia in urban, inner alpine and pre-alpine ambient air.
AB  - Passive samplers were used to monitor ammonia concentrations at rural inner
      alpine and pre-alpine, as well as urban, sites in Austria and Bavaria. Elevated
      concentrations were measured both at farms (up to 36 microg NH3 m(-3)) and at
      urban locations (up to 28 microg NH3 m(-3)). At urban locations a linear
      relationship between the traffic density and the NH3 concentration was found, but
      there was no marked seasonal trend. The highest ammonia concentrations were
      measured in a traffic tunnel (up to 78 microg NH3 m(-3)). The presence of
      livestock breeding or small scale alpine pastures resulted in elevated
      concentrations at the rural sites (8.1-12 and 2.5-4.6 microg NH3 m(-3),
      respectively), compared to the surrounding areas (3.1 and 0.9 microg NH3 m(-3)).
      Agriculture related sources are usually limited either spatially or seasonally.
      As the emissions were moderate in our case, a rapid removal and dilution of
      ammonia was possible and therefore the NH3 burden was only local. Sources related
      to traffic are more evenly distributed both geographically and seasonally. The
      WHO guideline, annual average concentration of 8 microg m(-3) for the protection
      of vegetation, was only exceeded at farms, at the urban station with the heaviest
      traffic and in the Tauerntunnel.

PMID- 11993758
TI  - Molecular characterisation of organic material in air fine particles (PM10) using
      conventional and reactive pyrolysis-gas chromatography-mass spectrometry.
AB  - Pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) was applied to study
      the composition of organic constituents in air particulate matter (PM10)
      collected inside an industrial area. A few milligrams of sampling filters
      containing air particles were pyrolysed at 700 degrees C directly (conventional)
      or after the addition of a derivatising reagent (tetramethylammonium hydroxide,
      TMAH, for pyrolysis-methylation; hexamethyldisilazane, HMDS, for pyrolysis
      silylation). Py-GC-MS was also applied to synthetic polymers (poly(styrene-co
      isoprene), polylimonene and polypinene) and vegetation samples (coniferous
      pollen, bark and resin) to identify markers indicative of possible precursors.
      Pyrolysates of PM10 showed the same suite of compounds in all the four seasons,
      dominated by hydrocarbons like styrene, limonene and clusters of isomeric alkenes
      with 14, 15 and 16 carbon atoms. Pyrolysis products of natural origin, including
      furaldehyde, benzeneacetonitrile, dehydroabietin and other diterpenoids were
      found, while no specific markers of synthetic rubbers were detected. The
      principal products released from reactive pyrolysis of PM10 were methyl or
      trimethylsilyl (TMS) derivatives of 1,6-anhydroglucose (levoglucosan), fatty
      acids, dehydroabietic acid and other resin acids along with hydroxy
      (di)carboxylic acids. Possible sources of the detected products (e.g. pine
      forest, biomass combustion) are discussed.

PMID- 11993759
TI  - Determination of isocyanates, aminoisocyanates and amines in air formed during
      the thermal degradation of polyurethane.
AB  - An air sampling method for the determination of isocyanates, aminoisocyanates and
      amines formed during the thermal degradation of polyurethane (PUR) is presented.
      The method is based on the collection of air samples using impinger flasks
      containing di-n-butylamine (DBA) in toluene with a glass fibre filter in series.
      Isocyanates are derivatized with DBA to urea derivatives, and amines are
      derivatized in a subsequent work-up procedure with ethyl chloroformate (ET) to
      carbamate esters. Amine, aminoisocyanate and isocyanate derivatives were
      characterized using liquid chromatography-time of flight mass spectrometry (LC
      TOFMS) and liquid chromatography-chemiluminescent nitrogen detection (LC-CLND).
      Quantification was performed by LC-MS, monitoring molecular ions [MH]+ in the
      electrospray mode. The instrumental detection limits for amines, aminoisocyanates
      and isocyanates were in the ranges 30-40, 2-3 and 3-70 fmol, respectively.
      Thermal degradation products of PUR were observed in high concentrations during
      welding in district heating pipes and PUR-coated metal sheets. Eleven
      isocyanates, three amines and five aminoisocyanates were identified. The
      concentrations of isocyanates, aminoisocyanates and amines in samples collected
      in the smoke close to the welding spot were in the ranges 150-650, 4-290 and 1-70
      ppb, respectively. In samples collected in the breathing zone, isocyanates and
      aminoisocyanates were observed in the ranges 9-120 and 4-19 ppb, respectively.
      The compounds were present in both gas and particle phases. Volatile compounds
      dominated in the gas phase, whereas less volatile compounds dominated in the
      particle phase. The method presented makes it possible to sample and determine
      amines and aminoisocyanates, in addition to isocyanates. The need to monitor
      these compounds is clearly illustrated by the high concentrations found during
      the thermal degradation of PUR.

PMID- 11993760
TI  - Observation of volatile and semi-volatile carbonyls in an Algerian urban
      environment using dinitrophenylhydrazine/silica-HPLC and
      pentafluorophenylhydrazine/silica-GC-MS.
AB  - Lower carbonyls and n-alkanals from C5 to C10 were measured from late autumn 2000
      to summer 2001 in two urban areas in the Algerian territory: Algiers and Ouargla.
      They were collected on silica cartridges coated with dinitrophenylhydrazine
      (DNPH) and pentafluorophenylhydrazine (PFPH), which were analysed by HPLC-UV and
      high-resolution GC-MS. respectively. The two methods were used in parallel
      samplings in a suburban Algiers site and provided consistent results for semi
      volatile congeners, as differences in the concentration data did not exceed 21%
      on average for individual carbonyl levels ranging from 0.0 to 0.5-2.6 microg m(
      3). Concentrations of formaldehyde up to 27 and 5 microg m(-3) were monitored
      during 10 h samplings in the daytime in Algiers and Ouargla, respectively;
      acetaldehyde reached values of 13 and 5 microg m(-3), whilst acetone was the most
      abundant ketone with peak levels of 14 and 4 microg m(-3), respectively. High
      night-time levels of lower carbonyls were also measured at both locations. Among
      the semi-volatile alkanals, the highest levels were observed in suburban Algiers
      for hexanal and nonanal (2.2 microg m(-3)) and in downtown Algiers for
      valeraldehyde (2.6 microg m(-3)), whilst in Ouargla only hexanal and nonanal
      levels within the C5-C10 fraction exceeded 1 microg m(-3). Moreover, benzaldehyde
      concentrations as high as 5 microg m(-3) were measured in the centre of Algiers.
      Algiers data are comparable with those found in photochemically polluted urban
      areas of Europe and the USA. Strong correlations between formaldehyde and
      acetaldehyde and between formaldehyde and benzaldehyde were observed; by
      contrast, acetone did not show any correlation with the lower aldehydes,
      suggesting the existence of carbonyl sources other than vehicular traffic.
      Diurnal variations of almost all carbonyls suggested that motor vehicles were the
      most important source in the winter, whereas photochemical production appeared to
      predominate during the summer.

PMID- 11993761
TI  - Sampling and analyses of colloids at the Drigg low level radioactive waste
      disposal site.
AB  - Water samples have been extracted from inside (from standpipes) and from outside
      (from boreholes) of the trenches at the low level radioactive waste disposal site
      at Drigg in Cumbria, UK. The samples were taken anaerobically from between 8.5
      and 10.0 m below the surface using a submersible pump at low flow rates to ensure
      that the waters in the standpipes and boreholes were maintained at constant
      levels. To ensure representative samples, the Eh, pH. conductivity, temperature,
      iron and dissolved oxygen concentrations of the waters were taken during initial
      purging and during sampling. The gross tritium, gross non-tritium beta, gross
      alpha and gamma activities of each sample were determined using suitable sample
      preparation and counting techniques. Samples were then anaerobically,
      sequentially filtered through 12 microm, 1 microm, 30 kDa and 500 Da filter
      membranes. The filtrates were analysed for gross alpha, gross non-tritium beta
      and gamma activities. SEM and STEM analyses were used to determine the colloid
      population. An energy dispersive analyser on the SEM was used to determine the
      major elements present in the colloids. UV-visible spectrophotometry,
      fluorescence spectrophotometry and high performance size exclusion liquid
      chromatography were used to analyse the waters before and after treatment with
      ion exchange materials to determine whether natural organic matter was present in
      the waters. Results showed that two major types of colloids (iron containing
      colloids and silicon containing colloids) were present in the waters. There were
      also a small number of other colloids that contain, as major elements, aluminium,
      calcium and chromium. Organic colloids were also present. The majority of the
      radioactivity in the waters was due to tritium. Waters taken from outside the
      trenches contained low levels of non-tritium beta activities and alpha activities
      which were lower than the minimum detectable amount. Waters taken from the
      trenches contained non-tritium beta activities and low levels of alpha emitters.
      Filtration of the trench waters showed that some of the alpha activity was
      retained by the 30 kDa and 500 Da membranes suggesting that this activity was
      associated with small colloids. Radioactivity was not found to be associated with
      colloids present in the waters taken from outside the trenches. Possible reasons
      for this observation could be that radionuclide bearing colloids have not yet
      reached the far-field or that the radionuclide concentration is diluted to below
      the minimum detectable amount. After concentrating two of the samples by factors
      of x20 and x 16 respectively, 2.4+/-0.1 and 0.6+/-0.1 Bq dm(-3) of 137Cs were
      measured.

PMID- 11993762
TI  - Chromium speciation and fractionation in ground and surface waters in the
      vicinity of chromite ore processing residue disposal sites.
AB  - Chromium concentrations of up to 91 mg l(-1) were found by ICP-OES for ground
      water from nine boreholes at four landfill sites in an area of S.E. Glasgow/S.
      Lanarkshire where high-lime chromite ore processing residue (COPR) from a local
      chemical works had been deposited from 1830 to 1968. Surface water concentrations
      of up to 6.7 mg l(-1) in a local tributary stream fell to 0.11 mg l(-1) in the
      River Clyde. Two independent techniques of complexation/colorimetry and speciated
      isotope dilution mass spectrometry (SIDMS) showed that Cr was predominantly
      (>90%) in hexavalent form (CrVI) as CrO4(2-), as anticipated at the high pH (7.5
      12.5) of the sites. Some differences between the implied and directly determined
      concentrations of dissolved CrIII, however, appeared related to the total organic
      carbon (TOC) content. This was most significant for the ground water from one
      borehole that had the highest TOC concentration of 300 mg l(-1) and at which < 3%
      of Cr was in the form of CrVI. Subsequent ultrafiltration produced significant
      decreases in Cr concentration with decreasing size fractions, e.g. <0.45 microm,
      < 100 kDa, <30 kDa and < 1 kDa by the tangential-flow method. As this appeared
      related more to concentrations of humic substances than of TOC per se, horizontal
      bed gel electrophoresis of freeze-dried ultrafilter retentates was carried out to
      further characterise the CrIII-organic complex. This showed for the main Cr
      containing fraction, 100 kDa-0.45 microm, that the Cr was associated with a dark
      brown band characteristic of organic (humic) matter. Comparison of gel
      electrophoresis and FTIR results for ultrafilter retentates of ground water from
      this borehole with those for a borehole at another site where CrVI predominated
      suggested the influence of carboxylate groups, both in reducing CrVI and in
      forming soluble CrIII-humic complexes. The implications of this for remediation
      strategies (especially those based on the addition of organic matter) designed to
      reduce highly mobile and carcinogenic Cr(VI)O4(2-) to the much less harmful CrIII
      as insoluble Cr(OH)3 are discussed.

PMID- 11993763
TI  - Assessing the removal of inorganic colloids and Cryptosporidium parvum from
      drinking water.
AB  - A new batch device that simulates the conditions in water and wastewater
      treatment plants and enables the study of low-concentration feeds is described.
      The application of this apparatus to the monitoring of the concentration of
      inorganic and/or biological contaminants is demonstrated, using kaolin particles
      and Cryptosporidium parvum oocysts, respectively. The rate of inorganic particle
      attachment to the static medium is found to be directly proportional to the
      initial influent concentration. On the other hand, Cryptosporidium parvum removal
      is found to be more effective in the presence of additional (kaolin) particles,
      and this is attributed to electrostatic interactions between oppositely charged
      layers on the absorbing medium. Accordingly, the addition of humic materials is
      found to inhibit the removal process, possibly by neutralizing the positive
      charge on the kaolin particles. The relevance of these results to existing water
      purification processes in general and to risk assessment of microbiological
      contamination in particular is discussed.

PMID- 11993764
TI  - Mechanistic studies of N-nitrosodimethylamine (NDMA) formation in chlorinated
      drinking water.
AB  - Studies were conducted to investigate the hypothesis that N-nitrosodimethylamine
      (NDMA) is a potential disinfection by-product specifically produced during
      chlorination or chloramination. Experiments were conducted using dimethylamine
      (DMA) as a model precursor. NDMA was formed by the reaction of DMA with free
      chlorine in the presence of ammonia and also with monochloramine. We proposed a
      mechanism for NDMA formation in chlorinated or chloraminated water, which does
      not require nitrite as in N-nitrosation. The critical NDMA formation reactions
      consist of (i) the formation of monochloramine by combination of free chlorine
      with ammonia, (ii) the formation of 1,1-dimethylhydrazine (UDMH) intermediate
      from the reaction of DMA with monochloramine followed by, (iii) the oxidation of
      UDMH by monochloramine to NDMA, and (iv) the reversible chlorine transfer
      reaction between free chlorine/monochloramine and DMA which is parallel with (i)
      and (ii). A kinetic model was also developed to validate the proposed mechanism.

PMID- 11993765
TI  - Patterns and levels of halogenated volatile compounds in Portuguese surface
      waters.
AB  - The present study focused on monitoring the concentration of 14 halogenated
      volatile organic compounds in surface waters, including sea, estuarine, river
      water and industrial effluents in order to determine the most ubiquitous
      compounds and their concentration levels, which were used to establish their
      geographical and temporal distribution. EPA Method 502, based on purge and trap
      techniques, was used. In this method volatile organic pollutants are extracted
      (purged) from the water sample by bubbling inert gas through the aqueous sample.
      Purged sample components are trapped in a cartridge containing the polymeric
      sorbent Tenax and, thereafter, the cartridge is heated and backflushed with
      helium to desorb the trapped sample components directly into a gas chromatograph
      with electron capture detector (GC-ECD). The linearity range of the method varied
      from 0.1 to 4 microg L(-1) with a limit of detection at the low microg L(-1)
      level. The present study consisted of a monthly monitoring of 46 points
      throughout Portugal, during 14 months. Chloroform was found in 50% of the samples
      analyzed, its presence being correlated to both agricultural and industrial
      activities. Other compounds detected were tetrachloroethylene, trichloroethylene,
      carbon tetrachloride and 1,2,4 trichlorobenzene, which were present in 10-20% of
      the samples at concentrations up to 18 microg L(-1). 1,1,2,2-Tetrachloroethane
      and its degradation product 1,1,2-trichloroethane were found in 5% of the
      samples, the levels of the latter being higher than those of the parent compound
      in most samples. Sporadic high concentrations of some volatile halogenated
      organic compounds were attributed to local uses as solvents.

PMID- 11993766
TI  - Performance of an in situ passive sampling system for metals in stormwater.
AB  - A passive sampler has been developed and is demonstrated in situ for urban
      runoff. The passive sampler is compared to conventional composite (time-dependent
      and flow-weighted) bottle sampling during and between storm events. The sampling
      was carried out at established stormwater stations; before and after a stormwater
      detention pond. In situ deployment of the passive sampler provides the metal
      concentrations, corresponding to the electrochemically available fraction of
      total metal, for time-dependent samples collected in parallel. The sampler
      provides improved accuracy compared to bottle sampling because contamination
      during sample transport and handling is minimised. Laboratory handling is reduced
      by direct analysis of the accumulated metals on the receiving membrane by laser
      ablation inductively coupled plasma mass spectrometry. Passive sampling also
      solves the problem of metal speciation change during transport to the laboratory,
      which is a potential problem for bottle samples. The low cost and convenience of
      the passive sampler and subsequent analysis should allow significantly more
      extensive spatial and temporal monitoring of metals in the aquatic environment
      than has previously been possible.

PMID- 11993767
TI  - Speciation of iron in river water using a specific catalytic determination and
      size fractionation.
AB  - A comprehensive speciation scheme was proposed for the speciation of iron in
      river water (0.45 microm filtrate). The speciation was based on the catalytic
      determination of reactive iron as Fe3+ and Fe(III)Li/(3 -in)+, where i = 1 or 2
      for a unidentate and i = 1 for a bidentate ligand, Ln-. The scheme incudes size
      fractionation and acid decomposition of the sample and determination of the
      coexisting species. The proposed scheme was applied to natural and artificial
      samples and acidified preparations of these. Resulting fractionation patterns of
      reactive and unreactive iron and of coexisting humic acid were useful for the
      characterization of iron species in the natural samples. The reactive iron in the
      molecular weight (Mr) > or = 10(4) fraction was associated with humic iron
      aggregates and estimated as iron complexed with them. The unreactive iron in this
      fraction dissociated in 0.1 M HCI and was estimated as iron in the aggregates of
      iron(III) hydroxide (s) and humic iron. From the fractionation results of the
      artificial sample, the reactive and unreactive iron in the Mr < 10(3) fraction
      may be formed by complexing simple anions like F- and C2O4(2-) at their naturally
      occurring concentration levels. The fractionation results also suggested that
      humic acid and Si contributed to the formation of reactive and unreactive iron in
      the Mr > or = 10(4) fraction.

PMID- 11993768
TI  - Quantifying the phenolic content of freshwaters using simple assays with
      different underlying reaction mechanisms.
AB  - Five different assays, Gibbs, Prussian Blue, Folin-Ciocalteau, fluorescence
      quenching of added phenol and precipitation of phenolics with bovine serum
      albumin (BSA) were investigated for their suitability in measuring the phenolic
      content of freshwaters. Phenol and a hydrolysable tannic acid were used as
      standards for monophenolics and polyphenolics, respectively. The individual and
      simultaneous application of both standards in doubly distilled water and filtered
      freshwater samples showed no matrix interference for the Gibbs, the Prussian Blue
      and the Folin-Ciocalteau assays. The quenching of phenol fluorescence and
      incomplete precipitation of added tannic acid in the freshwater samples were
      thought to originate from complexation. The Gibbs assay was specific for
      monophenolics, monohydroxybenzenes, with a Criterion of Detection (CoD) of 0.027
      mg l(-1). Evaluating the assay using twenty-two monophenolics of lignin origin
      showed, apart from phenol itself, the phenolic acids vanillic, isovanillic,
      ferulic and syringic to have a linear response between 0 and 10 microM. The other
      monophenolics were not responsive in the Gibbs assay. The oxidation-based assays
      Prussian Blue and Folin-Ciocalteau had a CoD of 0.169 and 0.025 mg l(-1),
      respectively. The ratio of response of both assays for each sample was taken as
      an indication of the degree of polymerisation of the phenolic content. The Folin
      Ciocalteau assay was used directly on the samples, on samples spiked with tannic
      acid at 2 and 4 mg l(-1), and after precipitation of phenolics with BSA. The
      difference in tannic acid equivalents before and after treatment, assayed the
      amount of protein precipitated phenolics. The results of all assays allowed
      differentiation between monophenolics (Gibbs), polyphenolics (Prussian Blue),
      total phenolics (Folin-Ciocalteau), complexation of added phenol and protein
      precipitated phenolics. The reaction mechanisms underlying the assays were
      matched onto those occurring during humification. The assays were applied to six
      filtered freshwater samples and two humic and two fulvic acids. The results
      showed a different pattern for each site and illustrated varying reactivity of
      the 'phenolic content' of freshwater.

PMID- 11993769
TI  - MTBE (methyl tertiary-butyl ether) in groundwaters: monitoring results from
      Germany.
AB  - In Germany information on the occurrence of MTBE in groundwaters is scarce. In
      order to assess the German situation, in 1999 a monitoring programme on MTBE in
      groundwater was set up. Within this survey 170 wells were examined, which are
      used as groundwater monitoring points or which are foreseen for drinking water
      extraction in emergency cases or for irrigation purposes. In rural areas MTBE was
      found only in 9% of all samples in concentrations above the limit of
      determination (LOD) of 0.05 microg L(-1). In urban areas MTBE was detected in 49%
      of all wells under investigation and the median concentration was calculated to
      0.17 microg L(-1). In one case a maximum MTBE concentration of almost 700 microg
      L(-1) was detected. As a first result of this survey one can conclude, that MTBE
      is regularly present in German groundwaters under urban areas. Although
      investigations about the occurrence of MTBE in German groundwaters have to be
      extended in future, this first snapshot can lead to the assumption, that MTBE
      concentrations due to diffuse sources are lower than the ones found in the USA.
      Nevertheless, e.g. accidental spills can lead to elevated MTBE concentrations.

PMID- 11993770
TI  - Organotin compounds in a Norwegian fjord. A comparison of concentration levels in
      semipermeable membrane devices (SPMDs), blue mussels (Mytilus edulis) and water
      samples.
AB  - Monitoring concentrations of organic pollutants in water is essential to predict
      effects and to initiate preventive steps. Results from the analysis of water
      samples provide snapshots of a situation, whereas monitoring using semipermeable
      membrane devices (SPMDs) provides a time-integrated picture of the concentration
      of pollutants in water. In this investigation, SPMDs, caged mussels and water
      samples were used to monitor the levels of organotin compounds in the inner
      Oslofjord, Norway, over a period of 12 weeks. The work-up procedure for the
      analysis of organotins was optimised, focusing on the clean-up procedure using
      gel permeation chromatography (GPC). By using several GPC columns, as much as 1 g
      of triolein could be employed. This reduces the background emission noise on the
      baseline, leading to an improvement in the detection limits. The main uptake of
      tributyltin (TBT) in mussels and SPMDs levelled off after 14 days. A longer
      uptake period was indicated for SPMDs at stations with a high water concentration
      of TBT (5-10 ng Sn L(-1)) compared with those with a low water concentration of
      TBT (approximately 1 ng Sn L(-1)). A concentration gradient was observed for
      water, SPMDs and mussels from the innermost station close to Oslo harbour to the
      station further out in the fjord, indicating that the three analysed matrices
      give approximately the same pollution gradient. The bioconcentration factor (BCF)
      for TBT in mussels was in the range 12-14 000 (wet weight) and, for SPMDs, 10-12
      000 (fat). A good correlation with the TBT water concentrations was achieved
      within a period of 14-30 days of exposure for mussels and after 2-3 months for
      SPMDs. A good correlation was also found between the TBT concentration in SPMDs
      and mussels at the end of the experiment. SPMDs can therefore be used to predict
      concentrations of TBT in both water and mussels.

PMID- 11993771
TI  - Chlorobiphenyl contaminants at Pladda and Garroch Head in the Firth of Clyde
      following the cessation of sewage sludge dumping.
AB  - Sewage sludge dumping at Garroch Head in the Firth of Clyde ceased on 31 December
      1998. Eighteen of the 209 chlorinated biphenyls (CBs) were measured in plaice
      livers, collected in 1999 and 2000, from the former Garroch Head dump site.
      Samples were also obtained from Pladda, a site reasonably remote from the former
      dump site but also in the Clyde, in 1999 only. These results were compared to the
      CB concentrations in plaice livers collected between 1992 and 1998 from Garroch
      Head and Pladda. Additional samples were also taken from a clean reference site,
      close to Colonsay. Concentrations of the congeners in the livers of fish caught
      at the former Garroch Head dump site in 1999 were marginally higher than those
      from Pladda, with a mean CB concentration of 1861 microg kg(-1) lipid in the
      Garroch Head plaice livers and 1725 microg kg(-1) lipid for the sample from
      Pladda. The mean CB concentration in the 2000 Garroch Head samples was 2253
      microg kg(-1) lipid. CB concentration in plaice livers from Colonsay were lower
      than both the Pladda and Garroch Head fish, with plaice livers from Colonsay
      giving a mean CB concentration of 1076 microg kg(-1) lipid in 1999 and 345.1
      microg kg(-1) lipid in 2000. The data was evaluated using principal component
      analysis (PCA). Pattern analysis was undertaken by normalising to the
      recalcitrant CB 153. There was an indication that the CB pattern has changed
      since the cessation of dumping with the proportion of tri- and tetra-chlorinated
      CBs being lower in plaice from Garroch Head than in previous years.

PMID- 11993772
TI  - The regulation of pesticides in Europe--Directive 91/414.

PMID- 11993773
TI  - Isotopic characterisation of lead deposited 1989-2001 at two upland Scottish
      locations.
AB  - The isotopic composition of lead collected with grass samples taken over the
      period 1989-2001 from plots at two upland locations (Glensaugh in north east and
      Hartwood in central Scotland) has been determined using thermal ionisation mass
      spectrometry. Although marked reductions in lead concentrations in grass were
      observed at Glensaugh in the initial three years, subsequently concentrations
      have remained relatively constant (1-3 microg g(-1)) in all plots to the present
      day. The one exception was a roadside plot at Hartwood which showed a large
      reduction from 1.0 microg g(-1) in 1999 to 0.2 microg g(-1) in 2000 following the
      abolition of petrol lead in the UK at the beginning of 2000. The total
      concentrations at this plot were consistently lower than those found at plots
      away from road traffic but exposed to the prevailing wind direction. The
      206Pb/207Pb ratio increased steadily at all the plots throughout the period of
      the study indicating the reducing influence of petrol lead but the changes were
      not as great as might be expected with the decrease in the use of leaded petrol.
      Assuming the collected lead had only two sources, petrol lead and a diffuse
      background "industrial" lead, the proportion of petrol lead was only in the range
      17-69% for roadside samples and 0-39% in other samples. A substantial proportion
      of deposited lead, therefore, now has its origin other than in petrol. Mixing
      curves indicate that whereas the lead deposited at Glensaugh could be defined by
      only two end members, that at Hartwood needs more than two components in the
      mixture. The results also suggest that although petrol lead has been eliminated,
      traffic is still a source of lead and another source defined as "traffic lead"
      should be considered.

PMID- 11993774
TI  - Heavy metal speciation in the composting process.
AB  - Composting is one of the more efficient and environment friendly methods of solid
      waste disposal and has many advantages when compared with landfill disposal on
      which the UK and Ireland are currently heavily dependent. Composting is a very
      complicated process involving intensive microbial activity and the detailed
      mechanisms of the process have yet to be fully understood. Metal speciation
      information can provide an insight into the metal-microbial interaction and would
      help in the evaluation of the quality of compost. This would facilitate the
      exploitation of composts in remediation of heavy metal contaminated land. In this
      work a systematic approach to metal speciation in compost has been taken by
      applying the three-step method for operationally defined metal speciation of
      soils and sediments, developed by the European Commission's Standards,
      Measurement and Testing Programme to monitor the change in metal speciation with
      time (up to 106 days) for four different waste composting processes. The results
      have shown that in general metals become less available for the first extraction
      step as the composting process proceeds. This implies that composting tends to
      redistribute the metals from more labile forms to more fixed forms which may
      explain why the application of composts could be useful for with heavy metal
      contaminated land. There are exceptions to this trend and in some cases, certain
      metals appear to behave differently depending on the source of the compost.

PMID- 11993775
TI  - Identification of dredged sediment-derived soils in the alluvial plains of the
      Leie and the Upper and Sea Scheldt rivers (Belgium) based on physico-chemical
      soil properties.
AB  - An approach was developed to identify surface soils affected by historical
      dredged sediment disposal in the alluvial plains of the Upper Scheldt, the Sea
      Scheldt and the Leie river. Dredged sediment-derived soils were identified based
      on field observations, comparative granulometric analyses and chemical analyses.
      Criteria developed were based on a comparison between reference data from 102
      aerobic soil samples of areas known to be affected by dredged sediment disposal
      and 104 samples from undisturbed alluvial soils along the studied rivers. A
      comparative grain size analysis with optical laser diffractometry between the A
      and C horizon proved useful for the identification of levelled-up sites. The
      chemical soil characteristics that were most useful in identifying dredged
      sediment-derived soils were CaCO3, sulfur (S), organic carbon (OC) and phosphorus
      (P) contents, electrical conductivity (EC), and the C/P and C/S ratios. Criteria
      for concluding the origin of an investigated soil were specific for the studied
      area, but the approach presented may provide useful guidelines for developing
      criteria valid for different regions.

PMID- 11993776
TI  - Non-selective signal loss in the 13C CPMAS NMR spectra of soil organic matter.
      Investigations of particle size fractions.
AB  - In 13C cross-polarisation magic angle spinning (CPMAS) spectra of soil samples,
      the paramagnetic soil constituents partially discriminate against the signal
      intensity of the 13C atoms. The aim of the present study was to check to what
      extent this signal depression depends on the paramagnetic ion content and if it
      is selective for a certain kind of carbon species. The spectra of a variety of
      particle size fractions of five quite different soils were recorded. A procedure
      was developed to compare quantitatively the relative carbon content of the
      different spectra. It was found that iron ions differ in their efficiency to
      discriminate against the carbon signals. Nevertheless a strong linear correlation
      between the detectability of carbon and cube root(wt.%Fe) was observed for both
      the total signal and the signal of the different carbon species as well. This
      underlines that iron ions mainly influence the depression of the 13C signal in
      soil spectra. Furthermore we found, that for C: Fe ratios of 1.5 to 20 non
      selective signal losses dominate. Despite a high percentage of non-detectable
      carbon (up to 90%), the 13C CPMAS spectra of our soil samples correctly reflect
      the relative composition of soil organic matter.

PMID- 11993777
TI  - Accelerated fractionation of heavy metals in contaminated soils and sediments
      using rotating coiled columns.
AB  - A new approach to performing an accelerated sequential extraction of trace
      elements from solid samples has been proposed. It has been shown that rotating
      coiled columns (RCC) earlier used in counter-current chromatography can be
      successfully applied to the dynamic leaching of heavy metals from soils and
      sediments. A solid sample was retained in the rotating column as the stationary
      phase under the action of centrifugal forces while different eluents (aqueous
      solutions of complexing reagents, mineral salts and acids) were continuously
      pumped through. The procedure developed is time saving and requires only 4-5 h
      instead of the several days needed for traditional sequential extraction (TSE),
      complete automation being possible. Losses of solid sample are minimal. In most
      cases the recoveries of readily bioavailable and leachable forms of Pb, Zn, and
      Cd are higher, if a dynamic extraction in RCC is used. Since naturally occurring
      processes are always dynamic, continuous extraction in RCC may help to estimate
      the contents of leachable forms and their potential risk for the environment more
      correctly than batch TSE. The Kersten-Foerstner and McLaren-Crawford leaching
      schemes have been compared, the former has been found to be preferable.

PMID- 11993778
TI  - Recycling of complexometric extractants to remediate a soil contaminated with
      heavy metals.
AB  - Equilibrations were performed with complexing reagent(s) to mobilise Cd, Cu, Mn,
      Ni, Pb and Zn from a contaminated urban soil. The metal-laden aqueous extract was
      treated with zero-valent magnesium (Mg0) or bimetallic mixture (Pd0/Mg0 or
      Ag0/Mg0) to precipitate the heavy metals from solution while liberating the
      chelating reagent(s). Post precipitation, the pH of aqueous supernatant fraction
      was readjusted to approximately 5 and the solution was re-combined with the soil
      particulates to extract more heavy metal pollutants. A sparing quantity of EDTA
      (10 mmoles) mobilised 32-54% of the 5 mmoles of heavy-metals from the soil with
      three cycles but only 0.1% of the iron was removed. Three successive extractions
      with a mixture of complexing reagents (3 mmoles), 1:1 EDTA plus HEDC [bis-(2
      hydroxyethyl)-dithiocarbamate], mobilised approximately 49% of the Pb,
      approximately 18% of the Zn and approximately 19% of the Mn burden but only 7% of
      the Cu, and 1% of the Fe from this soil. An appreciable fraction of the mobilised
      Pb and Cu and a portion of the Zn was cemented to the surfaces of the excess
      magnesium whereas virtually all of the Fe and Mn was removed from solution as
      insoluble hydroxides.

PMID- 11993779
TI  - Optimization of a multielement sequential extraction method employing an
      experimental design approach for metal partitioning in soils and sediments.
AB  - The optimisation of a simple multielement extraction method employing an
      experimental design approach is described. The method uses centrifugation to pass
      one extractant solution at varying pH through a contaminated soil sample. The
      nature and concentration of the acid, rate of centrifugation and time, number of
      sequential leachates and the ratio of extractant volume: sample weight have been
      studied in order to obtain the optimum conditions for extraction. A fractional
      factorial experimental design was performed, and the results were used to
      identify significance which was then evaluated by carrying out a central
      composite experimental approach. Once optimum conditions had been obtained,
      sequential leaches were analysed by ICP-AES and chemometrics were employed to
      identify the composition of each component. Comparisons have been made with
      previous studies and tentative assignments, based on well defined separated
      fractions and percentage compositions for individual elements, used to identify
      the different physico-chemical components in the sample.

PMID- 11993780
TI  - Parvovirus B 19 infection in adults.

PMID- 11993781
TI  - Mechanism of hypertension in Cushing's syndrome: possible role of 11beta
      hydroxysteroid dehydrogenase type 2 in kidneys and vascular cells.

PMID- 11993782
TI  - Mucosa-associated lympoid tissue (MALT) lymphoma and primary amyloidosis in the
      lung in Sjogren's syndrome.

PMID- 11993783
TI  - Somatic instability of CTG expansion in cancer tissue?

PMID- 11993784
TI  - Current therapy of chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder
      molecularly defined by the BCR-ABL gene and its products. The protein encoded by
      this chimeric gene is a constitutively activated tyrosine kinase that alters
      multiple signal transduction pathways inducing malignant transformation. Until
      recently, treatment options for patients with CML consisted of hydroxyurea,
      interferon-based therapies or allogeneic stem cell transplantation (alloSCT).
      Treatment decisions were generally based on the age of the patient and the phase
      of the disease. Recently, several new therapies have been developed that may
      change the natural history of CML and patient prognosis. In particular imatinib
      mesylate (ST1571, Gleevec) an oral Bcr-Abl kinase inhibitor, has demonstrated
      activity in all phases of CML, and may replace interferon and alloSCT as the
      initial therapy for this disease. Other agents and therapies with potential
      value, either alone or in combination, include polyethyleneglycol (PEG)
      interferon, homoharringtonine, decitabine, oral cytarabine, and growth factor
      modulation. In this article, we discuss the biological and clinical
      characteristics of CML, as well as the different therapeutic alternatives for
      patients with this disorder.

PMID- 11993785
TI  - Pathology and pathophysiology of chronic obstructive pulmonary disease.
AB  - A variety of pathological changes have been observed in the central airways,
      peripheral airways and lung parenchyma of patients with chronic obstructive
      pulmonary disease (COPD). The characteristic changes in the central airways
      include inflammatory cellular infiltration into the airway wall and mucous gland
      enlargement. In the peripheral airways, various morphological changes are
      observed, including mucous plugging, epithelial abnormalities, inflammatory
      cellular infiltrates, fibrosis and distortion; these changes lead to airway
      narrowing. In the lung parenchyma, emphysema defined as alveolar destruction and
      airspace enlargement is present. Although the major sites of airflow limitation
      in patients with COPD are most likely the peripheral airways, lesions in both the
      peripheral airways and the lung parenchyma contribute to chronic airflow
      limitations.

PMID- 11993786
TI  - Prognostic significance of the number of leads with ST depression during an
      anginal attack in high risk patients with unstable angina.
AB  - OBJECTIVE AND METHODS: We examined the prognostic significance of
      electrocardiographic predictors (number of leads with ST depression, maximal ST
      depression, QT dispersion), C-reactive protein, fibrinogen, myosin light chain 1
      and creatine kinase MB fraction in 62 patients with unstable angina showing ST
      depression during an anginal attack. RESULTS: During the 90-day follow-up period,
      15 patients (24%) exhibited new cardiac events (death, myocardial infarction or
      urgent revascularization). Using multivariate analysis, the number of leads with
      ST depression [relative risk 6.305 (95% confidence intervals 1.831-21.71),
      p<0.01] during an anginal attack was found to be an independent risk factor to
      predict cardiac events. Other predictors did not have prognostic significance.
      CONCLUSION: The number of leads with ST depression during an anginal attack is an
      independent risk predictor for new cardiac events in high risk patients with
      unstable angina.

PMID- 11993787
TI  - Comparative study of mediastinal emphysema as determined by etiology.
AB  - OBJECTIVE: To evaluate the difference in the clinical features of mediastinal
      emphysema as classified into three groups based on etiology; patients in whom it
      was spontaneous with unknown etiology (A group), those in whom it was secondary
      to bronchial asthma (B group), and those in whom it was secondary with other
      respiratory diseases (C group). PATIENTS: Forty-three cases (45 episodes) with
      mediastinal emphysema treated at Kawasaki Medical School Kawasaki Hospital
      between April 1985 and March 2000 (A group: 17 cases, B group: 17 cases, C group:
      9 cases). RESULTS: The average ages of the A and B groups were of little
      significance. Most of the patients in the A group were males with a thin body.
      Three patients in the A group had episodes of pneumothorax or mediastinal
      emphysema in their past history. Five patients in the A group had Hamman's sign
      on physical examination. In all of the patients in the C group, mediastinal
      emphysema was accompanied by subcutaneous emphysema, whereas only eight patients
      in the A group had subcutaneous emphysema. The prognosis was good for A and B
      groups because the mediastinal emphysema disappeared within 10 days, but was poor
      in the C group because its disappearance was very late compared with that in the
      other two groups and skin incision was required in three patients in the C group
      due to severe subcutaneous emphysema. CONCLUSIONS We suggest that the existance
      and kind of underlying diseases significantly affect the method of treatment and
      the prognosis.

PMID- 11993788
TI  - Primary central nervous system lymphoma: the clinical features and treatment of
      22 cases.
AB  - OBJECTIVE: To clarify the efficacy of chemotherapy after radiation therapy in
      immunocompetent patients with primary central nervous system lymphoma (PCNSL).
      PATIENTS AND METHODS: A retrospective analysis of 22 PCNSL patients was
      performed. Twenty-two patients were divided into a combined treatment
      (chemotherapy after radiation) group and a radiation group. The survival curves,
      calculated according to the Kaplan and Meier method, were compared using the Log
      rank and Wilcoxon statistical analyses. RESULTS: Eight patients were treated with
      radiation therapy alone, and their median survival time (MST) after diagnosis was
      21.9 months. Fourteen patients were treated with chemotherapy after radiotherapy.
      Six patients received chemotherapy consisting of cyclophosphamide, adriamycin,
      vincristine and prednisolone (CHOP), while 6 patients received carboplatin-based
      chemotherapy and 2 patients received methotrexate-based chemotherapy. The MST of
      these 14 patients was 34.4 months, which was not significantly better than that
      of the radiation therapy group (p=0.159). Leukoencephalopathy occurred in 3
      patients, who received whole brain radiation. CONCLUSION: The use of chemotherapy
      after radiation has up to now been thought to be a standard treatment modality
      but CHOP or carboplatin-based chemotherapy did not improve the survival time.

PMID- 11993789
TI  - Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the
      treatment of multiple myeloma.
AB  - OBJECTIVE: A newly designed combination chemotherapy for multiple myeloma, MMCP
      [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone
      (PSL)], was analyzed and compared with the results of our previous randomized
      trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine
      and PSL]. METHODS: MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM
      (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each
      cycle was repeated every 3 weeks. PATIENTS OR MATERIALS: From January 1991 until
      August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of
      Nagoya Cooperative Study Group were enrolled. RESULTS: Of the 87 evaluable
      patients, partial response rate for MMCP was 65.5% and was significantly higher
      than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%,
      p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the
      patients who attained plateau was significantly increased in the MMCP arm than in
      the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm
      (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than
      those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023
      by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5
      months, and for MMPP 22.9 months. No significant differences were observed with
      respect to adverse effects among the three regimens. CONCLUSION: The newly
      designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.

PMID- 11993790
TI  - A clinical study of adult human parvovirus B19 infection.
AB  - OBJECTIVE: We investigated the clinical aspects of adult human parvovirus (HPV)
      B19 infection. PATIENTS AND METHODS: We retrospectively reviewed the charts of 21
      consecutive patients [4 males, aged 32 to 43 years (average 38.0 years), and 17
      females, aged 15 to 43 (average 34.2)] with adult HPV B19 infection who visited
      our outpatient department between July 1997 and June 1998. All diagnoses of adult
      HPV B19 infection were based on positive anti-HPV B19 IgM antibody in serum
      and/or positive HPV B19 DNA in peripheral blood. RESULTS: The predominant signs
      and symptoms of the patients were: fever (81.0%), arthralgia/myalgia (61.9%),
      skin rash (47.6%), general fatigue (42.9%), lymph node swelling (38.1%) and edema
      (38.1%). Six patients had the following underlying diseases or complications:
      pregnancy, myoma uteri, cervical cancer of the uterus, lupus diathesis/
      endometriosis, hereditary spherocytosis, and multiple sclerosis. The following
      abnormal laboratory findings (more or less than normal limits) were observed:
      anemia (81.0%), leukopenia (33.3%), elevated transaminases (28.6%), and elevated
      lactate dehydrogenase (LDH) (57.1%). Six patients were considered to have
      persistent infection. CONCLUSION: HPV B19 can infect healthy adults and causes
      more predominant signs and symptoms (arthralgia, myalgia and fever) than in
      children, and adult HPV B19 infection can be suspected from the familial history
      and clinical findings. Accordingly, more attention must be paid to adult HPV B19
      infection, particularly when erythema infectiosum is prevalent in children.

PMID- 11993791
TI  - Chylomicronemia caused by lipoprotein lipase gene mutation related to a hyper
      response of insulin secretion to glucose.
AB  - A 39-year-old man with lipoprotein lipase (LPL) deficiency (height 177.7 cm, body
      weight 67 kg, and body mass index 21.2 kg/m2) showed severe hypertriglyceridemia
      (2,032 mg/dl). LPL activity and concentration were markedly low in postheparin
      plasma. LPL gene analysis revealed a homozygous mutation, Asp204 --> Glu in exon
      5. Fasting plasma glucose (81 mg/dl) and insulin (2.7 microU/ml) levels were
      normal. Plasma glucose pattern during oral glucose (75 g) tolerance test was
      normal, however 30 minutes after glucose-loading the insulin secretion
      unexpectedly increased to 89.4 microU/ml. These data suggested that
      chylomicronemia might be related to a hyper-response of insulin secretion to
      glucose without obesity.

PMID- 11993792
TI  - Preclinical Cushing's syndrome due to ACTH-independent bilateral macronodular
      adrenocortical hyperplasia with excessive secretion of 18
      hydroxydeoxycorticosterone and corticosterone.
AB  - A 64-year-old woman developed hypertension and hypokalemia, due to ACTH
      independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with
      excessive secretion of 18-hydroxydeoxycorticosterone and corticosterone. Plasma
      cortisol did not show a diurnal rhythm, and was not suppressed by dexamethasone
      (8 mg). Plasma cortisol responded to ACTH and was increased by hypoglycemia
      without modifying ACTH levels. Radiological studies demonstrated that adrenal
      glands were enlarged with macronodules. Although the patient exhibited a low
      plasma renin activity and aldosterone levels, hypokalemia and hypertension were
      observed. Hormonal findings would support the hypothesis that the tumor of AIMAH
      originated from cells of the upper zona fasciculata.

PMID- 11993793
TI  - Pulmonary MALT lymphoma with amyloid production in a patient with primary
      Sjogren's syndrome.
AB  - A 53-year-old woman was admitted to our hospital complaining of cough, low grade
      fever, chest pain and sicca symptoms. A chest radiograph showed an abnormal
      shadow and chest computed tomography revealed a tumor in left S6. She was
      diagnosed as Sjogren's syndrome by sialography and histological findings of
      labial biopsy. The surgically resected tumor specimen showed proliferation of
      lymphoid cells with lymphoepithelial lesions, which were positive for CD20 and
      kappa light chain. Kappa light chain-positive amyloid was found within the tumor.
      The tumor showed rearranged kappa light chain genes. The diagnosis was pulmonary
      mucosa associated lymphoid tissue lymphoma with amyloid production.

PMID- 11993794
TI  - A patient with myotonic dystrophy type 1 (DM 1) accompanied by laryngeal and
      renal cell carcinomas had a small CTG triplet repeat expansion but no somatic
      instability in normal tissues.
AB  - We examined (CTG)n lengths in various tissues from a 70-year-old man with
      myotonic dystrophy type 1 (DM 1) who had a small 60-70 (CTG), expansion in his
      leukocytes. He died of renal cell carcinoma 5 years after a total laryngectomy
      for laryngeal carcinoma. Southern blot and polymerase chain reaction analyses
      were done on tissues obtained at autopsy. In the various normal tissues, (CTG).
      lengths were almost all the same size, whereas the renal cell carcinoma and
      metastatic tissues had longer lengths. When compared with the lengths in
      leukocytes about 5 years previously, (CTG)n lengths in the normal tissues were
      the same size. These findings suggest that both somatic instability and age
      dependent (CTG). expansion in DM 1 patients with a small expansion may be less
      dominant than in patients with large expansions.

PMID- 11993795
TI  - Pulmonary actinomycosis followed by pericarditis and intractable pleuritis.
AB  - A case of pleuropericarditis caused by Actinomyces israelli is described. The
      patient first underwent left upper lobectomy because of pulmonary actinomycosis.
      Seven months later, cardiac tamponade developed. Culture of the bloody
      pericardial effusion resulted in positive growth of Actinomyces israeli. He was
      successfully treated with penicillin G, ampicillin, and minocyclin. However,
      right pleural effusion appeared two months later. Cultures of the effusion again
      yielded positive growth of the same bacteria. However, the strain had gained
      resistance to any antibiotics that had been effective before. Accordingly,
      pleurodesis with minocyclin was undertaken, which was fortunately effective for
      controlling the pleural effusion.

PMID- 11993796
TI  - Incidental medullary thyroid carcinoma in a case of Graves' disease.

PMID- 11993797
TI  - Effects of stage of harvest on the protein value of fresh lucerne for ruminants.
AB  - The ruminal degradation of dry matter (DM) and crude protein (CP) and the
      intestinal availability of CP of four fresh lucerne (Medicago sativa L.) samples,
      corresponding to a 3rd growing cycle and harvested at 2-week intervals, were
      determined. Rumen degradability, measured by the nylon bag technique, and rumen
      outflow rates were determined on three rumen-cannulated wethers. Intestinal
      digestibility was determined by the mobile bag technique on three duodenal
      fistulated wethers. Both groups of animals were fed a 2:1 lucerne hay to
      concentrate diet at an intake level of 40 g DM x kg(-1) BW0.75. The effective
      degradability (ED) of DM decreased with maturity in linear and quadratic form, as
      a consequence of a decrease in the soluble fraction and a similar increase in the
      undegradable materials. The resultant values were 0.795, 0.661, 0.600, and 0.576
      for harvests at 2, 4, 6, and 8 weeks. The ED of CP showed the same trend.
      However, the variations (values of 0.896, 0.832, 0.791, and 0.817, respectively),
      were moderate and mainly due to the reduction of the proportion of soluble CP.
      The intestinal digestibility of CP of all samples showed a downward trend with
      the increase in the ruminal incubation time, as modelled according to a logistic
      function. The undegraded CP digested in the gut (Di) and therefore the effective
      intestinal digestibility (EID) were derived from this function according to the
      rumen outflow of undegraded CP. The effects of maturity on the mean values of Di,
      expressed as a proportion of the original CP content, were the opposite of those
      recorded for the ED of CP. These values were 0.067, 0.102, 0.115, and 0.089 for
      samples harvested at 2, 4, 6, and 8 weeks, respectively. Nevertheless, when Di
      was expressed as g CP x kg(-1) DM, these values (18.0, 17.4, 17.1, and 14.3,
      respectively) decreased in linear form. The same trend was observed for EID
      values, which represent 0.641, 0.609, 0.549, and 0.488, respectively. The change
      of the digestion site produced by the reduction of ED of CP was also associated
      with an increase in the undigested CP (values of 0.037, 0.066, 0.094, and 0.094,
      at the four harvesting times).

PMID- 11993798
TI  - Four years of induction/synchronization of estrus in dairy goats: effect on the
      evolution of eCG binding rate in relation with the parameters of reproduction.
AB  - Ninety-eight Alpine goats of two herds were followed over 4 years in a program of
      annual artificial insemination after estrus induction/synchronization, including
      progestagen administration (vaginal sponge) followed by prostaglandin analog and
      equine chorionic gonadotrophin (eCG) 48 h before sponge removal. Goats were
      sampled every 4 hours from the 16th to the 56th following sponge removal, for
      determination of LH surge and tested for estrus by the presence of a buck. Seven
      days after AI, endoscopic examination of the ovaries was performed to determine
      the number of corpus lutea. Pregnancy diagnosis was performed at day 21-22 post
      AI by determination of plasma progesterone and at day 40-45 by ultrasonography.
      Parturition, number and sex of kids were recorded. All the goats were sampled
      before and after each treatment, for anti-eCG antibodies screening. Statistical
      analysis of the results clearly established a significant effect of the
      treatments on anti-eCG antibodies. Time of estrus and LH surge were significantly
      different between herd. The antibodies significantly delayed the time of coming
      out of estrus as well as the time of LH surge. Two antagonistic effects were
      evidenced: first, the delayed of time of estrus and time of LH surge in relation
      with the immune reaction to eCG; secondly, the ahead of time of estrus and time
      of LH surge during the years of treatment, identical to both herd. The antibodies
      negatively influenced the percentage of ovulating females as well as kidding
      rate. Finally, no effect of antibodies on prolificacy was found.

PMID- 11993799
TI  - Cereal supplementation modified the fibrolytic activity but not the structure of
      the cellulolytic bacterial community associated with rumen solid digesta.
AB  - 4 ruminally cannulated cows were fed a forage diet (93% hay + 7% straw) and a
      mixed diet (33 % hay + 7% straw + 40% barley) in a 2 x 2 crossover experimental
      design. In sacco degradation of forage, fibrolytic activities (polysaccharidases
      and glycosidases) of the solid-associated bacteria (SAB), and distribution of the
      3 main cellulolytic bacterial species (Fibrobacter succinogenes, Ruminococcus
      albus, Ruminococcus flavefaciens) were determined for both diets. Barley
      supplementation decreased the hay degradation rate and mainly the
      polysaccharidase activities of the SAB (30% on average). The sum of rRNA of the 3
      cellulolytic bacterial species represented on average 17% of the total bacterial
      signal and R. albus was the dominant cellulolytic bacterial species of the 3
      studied. Barley supplementation did not modify the proportion of the 3
      cellulolytic bacteria attached to plant particles. The negative effect of barley
      on the ruminal hay degradation rate is due to a decrease in fibrolytic activity
      of the SAB, and not to a modification of the balance of the three cellulolytic
      bacterial species examined.

PMID- 11993800
TI  - Factors influencing oocyte and embryo quality in cattle.
AB  - Following in vitro maturation, approximately 90% of immature bovine oocytes will
      reach metaphase II and extrude the first polar body; approximately 80% will
      undergo fertilization and cleave, at least once, to the two-cell stage. However,
      only about 30-40% will ever reach the blastocyst stage. This would suggest that
      the post-fertilization part of the process of in vitro embryo production, the
      longest part, is the main period determining blastocyst yield. The experiments
      described in this paper clearly demonstrate that this is. in fact, not the case
      and that it is events further back along the developmental axis that determine
      the proportion of immature oocytes reaching the blastocyst stage. The results
      also show, however, that the post-fertilization culture period is of profound
      importance in determining the equality of those blastocysts that do develop, with
      those produced in vitro consistently being of inferior quality to their in vivo
      produced conterparts. The challenge for the future is to modify our conditions of
      post-fertilization embryo culture in an attempt to mimic those that occur
      naturally in vivo and in that way improve blastocyst quality.

PMID- 11993801
TI  - Risks of transmissible diseases in relation to embryo transfer.
AB  - Realizing the potential of Embryo transfer (ET) for rapid, cheap and widespread
      dissemination of genetic material, the risk of transmission disease through the
      embryos must be considered. The aim of this paper is to evaluate theses risks at
      each step of production, storage and transfer. The pathogen agent may potentially
      originate from the donor male (semen) or the donor female (oocytes, embryos) and
      finally from the environmental conditions. As the differences between in vivo and
      in vitro derived embryos have been well described, evaluation of the potential
      risks should be assessed separately for in vivo and in vitro produced embryos.
      Even if this paper insist on the diseases or diseases agents that are more
      questionable, it clearly appears that ET remains the more safety way to transfer
      gene, provided prevention measures are properly handled (use of donor that are
      specific pathogen free, washing of embryos, additional treatment...) and
      furthermore it can be easily seen as the best way to prevent some disease
      transmissions (TSEs, leukosis, foot-and-mouth disease...).

PMID- 11993802
TI  - Rendez-vous in the oviduct: implications for superovulation and embryo transfer.
AB  - The meeting between the maternal and paternal gametes is dependant upon a number
      of complicated processes. On the maternal side it involves maturation of the
      oocytes under the influence on both peripheral and follicular endocrine factors.
      Deviations in the normal pattern of maturation will lead to ovulation of inferior
      oocytes. On the paternal side the transport of spermatozoa in the female genital
      tract following mating is an area of great importance. The establishment of the
      sperm reservoir in the isthmus is dependant upon a number of factors
      (intracellular calcium concentrations, oligo-saccharides, change in estradiol:
      progesterone ratio in the afferent blood supply). Alterations of the normal micro
      environment may disturb both binding, release and transport as a whole. The
      process of fertilization occurs in the ampullar region of the oviduct and it
      involves several well tuned steps: binding to the zona pellucida where the
      acrosome reaction takes place, penetration, fusion between the oolemma and the
      sperm plasma membrane, activation with the release of the cortical granules,
      decondensation of the sperm chromatin, pronucleus formation and finally syngamy
      where the two pronuclei fuses. The egg will experience the first cleavage shortly
      thereafter. Superovulation may disturb a number of these processes including
      oocyte maturation (arrest at MI) and sperm and zygote transport in the oviduct
      caused by the deviant endocrine environment, thus leading to a higher incidence
      of lack of fertilization and poor embryos quality.

PMID- 11993803
TI  - Phthalate monoesters levels in the urine of young children.

PMID- 11993804
TI  - Lead exposure at a covered outdoor firing range.

PMID- 11993805
TI  - Persistent organochlorine pesticide levels in maternal blood serum, colostrum,
      and mature milk.

PMID- 11993806
TI  - Estrogenicity of biphenylols: activity in the yeast gene activation assay.

PMID- 11993807
TI  - Mercury in human blood, urine, hair, nail, and fish from the Ankobra and Tano
      River Basins in southwestern Ghana.

PMID- 11993808
TI  - Urban ambient air quality and its management strategy for a metropolitan city in
      India.

PMID- 11993809
TI  - Adrenal corticotropin hormone and nestling bald eagle corticosterone levels.

PMID- 11993810
TI  - Teratogenicity of hexavalent chromium in rats and the beneficial role of ginseng.

PMID- 11993811
TI  - Effect of propoxur on humoral and cell-mediated immune responses in albino rats.

PMID- 11993812
TI  - Levels of p,p'-DDE in liver of predatory birds from Calabria, Italy.

PMID- 11993813
TI  - Heavy metal concentrations in surface soils from Mexico City.

PMID- 11993814
TI  - Sediment quality of wetlands in Coimbatore, Tamilnadu, India.

PMID- 11993815
TI  - Degradation of alachlor in water and tropical soils of India.

PMID- 11993816
TI  - Evaluating the safety of beta-cyfluthrin insecticide for usage in eggplant
      (Solanum melongena L.) crop.

PMID- 11993817
TI  - Behaviour of beta-cyfluthrin and imidacloprid in mustard crop: alternative
      insecticide for aphid control.

PMID- 11993818
TI  - Field dose-response approach (DRAC-"dose-resposta para avaliacao da
      contaminacao") as a tool for environmental mercury contamination assessment in
      fish.

PMID- 11993819
TI  - Toxicity of gadolinium to some aquatic microbes.

PMID- 11993820
TI  - Impact of cadmium and zinc prior exposure on 110msilver, 58+60cobalt and
      137cesium uptake by two freshwater bivalves during a brief field experiment.

PMID- 11993821
TI  - Benzo-a-pyrene residues in liver and in bile of fish following oral exposure.

PMID- 11993822
TI  - Metal concentrations in the vertebrae of the dogfish, Centroscymnus crepidater
      (Bocage and Capello) and Deania calcea (Lowe).

PMID- 11993823
TI  - Mercury in a marine trophic chain.

PMID- 11993824
TI  - Lead and cadmium in selected species of shrimp around the Mumbai coast, India.

PMID- 11993825
TI  - How long do emergency physicians' careers last?

PMID- 11993826
TI  - Towards longevity in emergency medicine.

PMID- 11993827
TI  - Uvulitis and partial upper airway obstruction following cannabis inhalation.
AB  - The use of cannabis in our society is a common problem and the subject of much
      medical and political debate. We present a case in which a 17-year-old male
      regular cannabis user developed a large swollen uvula (uvulitis) and partial
      upper airway obstruction after smoking cannabis. Symptoms resolved with the
      administration of corticosteroids and antihistamines.

PMID- 11993828
TI  - Sustained-release bupropion overdose: a new entity for Australian emergency
      departments.
AB  - Bupropion hydrochloride (Zyban, Glaxo Wellcome Australia, Melbourne, Vic.,
      Australia) was released in Australia in November 2000 as adjunctive therapy to
      assist with smoking cessation, having previously been used as an antidepressant
      in the US since 1989. The toxicity profile of bupropion hydrochloride in overdose
      differs considerably from other antidepressants, with prominent neurological
      manifestations and little cardiovascular toxicity. A case of bupropion overdose
      demonstrating the typical toxic syndrome is presented, together with a review of
      the literature and a discussion of the magnitude of the demand for bupropion and
      of the potential differences in presentation of overdoses in Australia.

PMID- 11993829
TI  - Impact of a telephone call centre on emergency department workload.

PMID- 11993830
TI  - Small emergency departments: reappraising 'critical mass'.

PMID- 11993831
TI  - Indigenous suicide in Australia, New Zealand, Canada, and the United States.
AB  - This paper reviews literature on self-harm and suicide among Indigenous
      populations in four nations with histories of British colonization, with a more
      detailed exploration of patterns and primary care considerations in Australian
      Aboriginal and Torres Strait Islander populations. Issues of definition, under
      reporting, lack of reporting, varying coronial practices and the influence of
      race on investigative procedures make comparisons of suicide rates among
      indigenous populations problematic. However, international interpretations
      highlight the impact of the breakdown of cultural structures and historical
      processes associated with colonization. Recent studies suggest that the
      predisposition to suicide by vulnerable young people is influenced not only by
      absolute living standards but also how they view their circumstances relative to
      those around them. The complexity of associations with mental disorder, alcohol
      use and 'meaning' in an indigenous context are considered. Responses in terms of
      prevention and treatment are presented, highlighting the importance of hospital
      based practitioners as the likely first point of contact. The article concludes
      by outlining considerations in the primary care management of indigenous self
      harm.

PMID- 11993832
TI  - A global view of suicidal behaviour.
AB  - Suicidal behaviour is a major public health problem. There is no one explanatory
      theory of suicidal behaviour, and various combinations of sociological and
      biological/medical interventions are required to reduce associated mortality and
      morbidity. The importance of primary prevention varies from community to
      community, and may have an impact at the population level. However, individual
      suicidal persons always require optimum assessment and management and that is
      usually provided by primary care and emergency physicians. This paper provides an
      overview of issues to be addressed in the assessment and management of suicidal
      patients.

PMID- 11993833
TI  - Gender issues in youth suicidal behaviour.
AB  - There are gender differences in youth suicidal behaviour that are evident in
      childhood and persist throughout adolescence and young adulthood. In Western
      countries, young females are twice as likely as males to report suicidal ideation
      and suicide attempt behaviour. However, despite the fact that females make more
      suicide attempts, males are three- to fourfold more likely to die by suicide than
      females. This paper reviews the epidemiological evidence for gender differences
      in suicidal ideation, attempted suicide and completed suicide among young people
      and explores possible reasons for the observed differences. These reasons include
      differences in methods, intent, ascertainment, the cultural acceptability of
      suicide, psychopathology (including substance abuse, mood disorder, externalizing
      behaviours and propensity to violence), and psychosocial differences between
      males and females. While it is often suggested that gender differences in youth
      suicidal behaviour may be explained solely or predominantly by method choice,
      careful examination suggests that the issues are much more complex. In fact,
      females may enjoy more protection from suicide than males in a number of areas.

PMID- 11993834
TI  - Complaints from emergency department patients largely result from treatment and
      communication problems.
AB  - OBJECTIVE: Emergency department patient complaints are often justified and may
      lead to apology, remedial action or compensation. The aim of the present study
      was to analyse emergency department patient complaints in order to identify
      procedures or practices that require change and to make recommendations for
      intervention strategies aimed at decreasing complaint rates. METHODS: We
      undertook a retrospective analysis of patient complaints from 36 Victorian
      emergency departments during a 61 month period. Data were obtained from the
      Health Complaint Information Program (Health Services Commissioner). RESULTS: In
      all, 2,419 emergency department patients complained about a total of 3,418
      separate issues (15.4% of all issues from all hospital departments). Of these,
      1,157 complaints (47.80%) were received by telephone and 829 (34.3%) were
      received by letter; 1,526 (63.1 %) complaints were made by a person other than
      the patient. Highest complaint rates were received from patients who were female,
      born in non-English-speaking countries and very young or very old. One thousand
      one hundred and forty-one issues (33.4%) related to patient treatment, including
      inadequate treatment (329 issues) and inadequate diagnosis (249 issues); 1079
      (31.6%) issues related to communication, including poor staff attitude,
      discourtesy and rudeness (444 issues); 407 (11.9%) issues related to delay in
      treatment. Overall, 2516 issues (73.6%) were resolved satisfactorily, usually by
      explanation or apology. Only 59 issues (1.7%) resulted in a procedure or policy
      change. Remedial action was taken in 109 issues (3.2%) and compensation was paid
      to eight patients. CONCLUSIONS: Communication remains a significant factor in
      emergency department patient dissatisfaction. While patient complaints have
      resulted in major changes to policy and procedure, research and intervention
      strategies into communication problems are indicated. In the short term, focused
      staff training is recommended.

PMID- 11993835
TI  - Outcome of emergency department patients with delayed admission to an intensive
      care unit.
AB  - OBJECTIVE: To compare 30 day mortality, length of stay and cost for adult
      emergency department patients with a delay in intensive care unit admission of up
      to 24 h with a group of patients admitted directly from the emergency department
      to the intensive care unit. METHODS: Retrospective cohort study in a 300-bed
      university affiliated teaching hospital. One hundred and twenty-two adult
      emergency department patients admitted to the intensive care unit either directly
      from the emergency department (direct group) or within 24 h of ward admission
      (delayed group) were identified. The main outcome measures investigated were 30
      day mortality, length of stay and cost. RESULTS: Thirty day mortality in the
      delayed group was significantly higher, the risk ratio being 2.46 (95% confidence
      interval 1.2-5.2). The length of stay and cost were similar in the direct and
      delayed groups. Baseline estimate of risk of death derived from the mortality
      probability model calculated from the emergency department data was similar for
      the two groups (P =0.10). Emergency department triage categorization and
      emergency department staff seniority was significantly different (chi2 for
      trends, P = 0.002 and 0.023, respectively), with patients in the delayed group
      more likely to be triaged as less urgent and to be initially assessed by junior
      staff. CONCLUSION: Our study shows that patients transferred to the intensive
      care unit within 24 h of ward admission from the emergency department had a
      significant increase in 30 day mortality compared with patients admitted to the
      intensive care unit directly from the emergency department, but no difference was
      found in terms of length of stay and cost.

PMID- 11993836
TI  - Most head injury related motorcycle crash deaths are related to poor riding
      practices.
AB  - OBJECTIVE: To report the characteristics of head injury related motorcycle crash
      deaths. METHODS: Motorcycle crash deaths with head injury (Abbreviated Injury
      Severity score > or = 2) between 1 January 1998 and 31 December 1999 were
      identified from the Western Australia State Coronial Database. Demographics,
      incident and death locations, type of incident and role of unsafe riding
      behaviour were examined. RESULTS: There were 39 deaths analysed (35 motorcycle
      riders and four pillion passengers). The median age was 29 years (range 9-64
      years), with 22 deaths (56.4%) in the range 15-29 years and 92.3% of those killed
      being male. Twenty-one motorcycle crashes were single-vehicle crashes (53.8%).
      There were 25 deaths at scene (64.1%). Ethanol was implicated in 12 cases (30.8%)
      and other drugs were implicated in 11 cases (28.2%). Speeding was implicated in
      12 cases (30.8%) and a lack of appropriate safety equipment was implicated in
      five cases (12.8%). One or more of the unsafe practices above was identified in
      23 cases (59%). Overall, there was no difference in the rate of unsafe practices
      in single-vehicle incidents compared with incidents involving another vehicle (P
      = 0.342). Ethanol was associated with 10 single motorcycle incidents (47.6%)
      compared with two (11.1%) involving another vehicle (P = 0.018). Unsafe practices
      were involved in 76% of at-scene deaths, compared with 28.6% in those surviving
      to hospital (P = 0.007). CONCLUSION: A large proportion of head injury related
      motorcycle crash deaths are related to the unsafe behaviour of motorcyclists. A
      preventative campaign focusing on young male motorcycle riders and unsafe driving
      behaviour may reduce this death toll.

PMID- 11993837
TI  - Paediatric sedation in emergency department: what is our practice?
AB  - OBJECTIVES: The aim of the present study was to document the use of sedation in
      paediatric patients in emergency departments within Australia and New Zealand.
      METHODS: A questionnaire was sent to 54 emergency departments throughout
      Australia and New Zealand. RESULTS: A total of 45 departments (83%) responded to
      the survey. Because the adult departments (n 5) reported few paediatric
      attendances, they were not included in the analysis. Thirty-nine of 40
      departments (97.50%) reported using sedation in children. Midazolam was used most
      frequently (77%) for sedation. There was marked variation in the route of
      delivery and the dose of midazolam used. Ketamine was reported as the most
      efficacious agent used, but it was used only in 12% of cases. Formal guidelines
      existed in all paediatric departments but only in 58% of mixed departments, and
      formal discharge criteria were used in only 52% of all departments. The use of
      topical anaesthesia in wound closure was reported in only 3,000 of departments.
      CONCLUSIONS: There exists wide variation in practice regarding the use of
      sedation in children in emergency departments throughout Australia and New
      Zealand. Thus, the development of adequate guidelines, including discharge
      instructions and the use of topical agents, will improve sedation for children.

PMID- 11993838
TI  - A study of triage of paediatric patients in Australia.
AB  - OBJECTIVES: To describe the triage of children in a sample of mixed and
      paediatric emergency departments in Australia in 1999 and to measure the inter
      rater reliability of the National Triage Scale when used by triage nurses for the
      triage of paediatric patients. METHODS: A questionnaire was sent to 11 hospitals,
      including one paediatric and one mixed emergency department, in each state
      studied. Triage nurses were asked to assess 25 paediatric patient profiles and to
      assign appropriate triage categories to each profile. The number of responses
      within the modal triage category (concurrence), the percentage of responses with
      a concurrence of at least 50% and the number of responses within one triage
      category of the modal response (spread) of responses were measured. Triage data
      for 1999 from the same emergency departments were collected and numbers of
      children seen and admitted in each triage category were described. The patterns
      of distribution of triage categories for specific paediatric diagnoses (triage
      'footprints') were also described. Data from mixed emergency departments were
      grouped and compared with data from paediatric emergency departments and any
      differences were described. RESULTS: Seventy-eight nurses in 10 hospitals
      responded to the questionnaire. Sixty-three per cent of all responses had a
      concurrence of greater than 50%. Ninety-four per cent of patient profiles were
      triaged to within one triage category of their modal response. Nurses in
      paediatric emergency departments (concurrence greater than 50% for 79% of
      responses) were significantly more consistent in their use of the National Triage
      Scale compared with nurses in mixed emergency departments (concurrence greater
      than 50% for 50% of responses). Paediatric emergency department triage nurses
      were more likely to use the full range of the National Triage Scale and were
      fourfold as likely to allocate triage categories 4 and 5 to patient profiles.
      Paediatric hospitals allocated patients to triage categories 4 and 5 for an
      average of 710 of presentations compared with 47% for mixed emergency
      departments. Specific diagnoses had characteristic distributions of triage
      categories, with similar differences seen when comparisons were made between
      mixed and paediatric emergency departments. CONCLUSION: Use of the National
      Triage Scale for the triage of paediatric patients by triage staff is not
      consistent and there are significant differences between the triage practices of
      paediatric and mixed emergency departments.

PMID- 11993839
TI  - Options in prehospital analgesia.
AB  - BACKGROUND: Prehospital analgesia options for paramedics have been limited due to
      the difficulty in achieving safe and effective pain relief without compromising
      transportation to hospital. The present paper identifies the analgesia methods
      currently available in the prehospital setting so as to evaluate the various
      options and highlight areas for future research. METHODS: A literature review of
      Medline and Embase databases from 1966 until the present was undertaken. Further
      hand searching of all the references identified in these papers was also
      performed. All current literature was analysed and categorized according to one
      of four levels of evidence using National Health and Medical Research Council of
      Australia guidelines (1999). RESULTS: There is a paucity of randomized control
      trials relating to prehospital analgesia. All published literature was level III
      or IV prospective or retrospective studies. Drug options used included nitrous
      oxide/oxygen mixtures, intravenous/intramuscular nalbuphine, intravenous tramadol
      and intravenous pure opiate agonists. CONCLUSIONS: The evidence supporting
      analgesic options in the prehospital setting is limited. There are few published
      data in this area despite the inadequacy of pain relief being recognized as a
      weakness in prehospital care. Prehospital analgesia is an area worthy of
      innovative methods for the administration of safe and effective analgesics
      without significant impact on transport times. Such methods should be
      prospectively evaluated in well-constructed trials.

PMID- 11993840
TI  - Youth suicide in Australasia.

PMID- 11993841
TI  - Mild snake envenomation.
AB  - Snake bite envenomation typically requires treatment with effective first aid and
      antivenom. There is a spectrum of envenomation seen, which includes mild
      envenomation, but this has not been reported previously. We report two cases of
      mild envenomation and describe the changes in laboratory coagulation values. The
      patients had a benign clinical course without receiving antivenom. We strongly
      recommend that if clinicians are considering not treating any envenomated
      patients with antivenom, they do so only on expert advice.

PMID- 11993842
TI  - Massive overdose with controlled-release carbamazepine resulting in delayed peak
      serum concentrations and life-threatening toxicity.
AB  - INTRODUCTION: Peak serum levels following overdose with immediate-release
      formulations of carbamazepine have been reported to occur up to 2 days
      postingestion. We report a case of poisoning with carbamazepine controlled
      release resulting in peak levels 96 h postingestion. CASE REPORTS: A 31-year-old
      female presented following a suspected polypharmacy overdose. She was
      haemodynamically stable with a Glasgow Coma Scale score of 3 and was
      endotracheally intubated in the emergency department. A single-dose of activated
      charcoal was administered on admission and her neurological status improved
      gradually Results of qualitative urine drug screen available 24 h postadmission
      to the intensive care department revealed benzodiazepines and carbamazepine. The
      serum carbamazepine concentration at this time was 66 micromol/L (therapeutic 17
      42 micromol/L). A history of therapy with controlled-release carbamazepine was
      discovered. Repeat-dose activated charcoal and whole-bowel irrigation were
      commenced, but poorly tolerated. Serum carbamazepine levels continued to rise and
      gastrointestinal tract decontamination was ceased due to the presence of an
      ileus. By day 4, the serum carbamazepine concentration peaked at 196 micromol/L.
      This was associated with coma, generalized intermittent seizure activity and
      hypotension. Charcoal haemoperfusion was commenced due the presence of end-organ
      toxicity and failed gastrointestinal tract decontamination. Serum carbamazepine
      concentrations fell from 176 to 106 micromol/L after 1 h of haemoperfusion and
      the patient was rousable to voice and could obey commands at this time. She
      confirmed ingestion of 300 Tegretol-CR (200 mg) on extubation and was discharged
      without long-term sequelae. CONCLUSION: Unrecognized poisoning with controlled
      release carbamazepine has the potential to produce significant delayed
      carbamazepine toxicity and delayed peak serum carbamazepine concentrations. This
      may occur much later than previously reported with immediate-release
      carbamazepine preparations.

PMID- 11993843
TI  - Doctors beware: why a patient complains is not always what it seems.

PMID- 11993844
TI  - Small emergency departments: does size matter?
AB  - An emergency department provides care for a full spectrum of undifferentiated
      disorders and its size may influence how well it can do so. Outcomes research in
      emergency medicine is limited, although outcomes in severe trauma and acute
      coronary syndromes have been shown to be influenced by available facilities and
      expertise. A department can be too small to provide the full spectrum of
      emergency care, as has been documented with General Practice Casualty Units. Some
      research suggests that a critical mass is required to ensure acceptable outcomes.
      Small departments may operate in a hierarchical system, led by teaching hospitals
      setting practice standards. However, these may be opinion as much as evidence
      based and not broadly applicable as a universal practice standard. Small
      departments can be overwhelmed by trauma and other major cases or when the
      teaching hospital is unable to accept emergency patients or transfers because
      they are operating at capacity. Further outcomes research and audit of individual
      hospitals is required to determine a minimum optimum size for emergency
      departments.

PMID- 11993845
TI  - The effects of intravenously administered methylxanthine preparations on the
      glycoconjugate composition of goblet cells in rabbit tracheal epithelium.
AB  - Effects of methylxanthine derivatives, which are inhibitors of phosphodiesterases
      I-IV used against bronchial asthma, on the composition of glycoconjugates in
      goblet cells were evaluated in tracheal epithelium of rabbits at 15 and 30 min
      after intravenous administration of aminophylline (Syntophyllin) and a mixture of
      etophylline and theophylline (Oxantil), respectively. Percentages of tracheal
      goblet cells containing neutral, total acidic, sulphated acidic, and sialylated
      acidic glycoconjugates were assessed using both conventional and lectin
      histochemistry. No significant changes were found in both experimental groups at
      15 min after exposure. A significant decrease in percentage of alpha(2-3)
      sialylated glycoconjugate-containing goblet cells occurred at 30 min after
      administration of Syntophyllin only. It is concluded that the mucus composition
      of tracheal goblet cells has been affected by the bronchospasmolytic drug
      Syntophyllin but not by the vasodilator drug Oxantil.

PMID- 11993846
TI  - Myopathy-dependent changes in activity of ATPase, SDH and GPDH and NOS expression
      in the different fibre types of hamster muscles.
AB  - Proximal (vastus lateralis) and distal (gastrocnemius) muscles of 100-day-old
      normal and myopathic BIO TO-2 hamsters were analysed to study the effects of
      myopathy on the different muscle fibre types: SO (slow oxidative), FOG (fast
      oxidative glycolytic) and FG (fast glycolytic). Cytophotometric measurements of
      enzyme activities (myofibrillic adenosine triphosphatase, succinate dehydrogenase
      and glycerol-3-phosphate dehydrogenase), Western blot analysis of nitric oxide
      synthase (NOS) I, II, III isoforms and NOS II immunohistochemistry were
      performed. The following alterations were found in myopathic muscle fibres: all
      fibre types of both proximal and distal myopathic muscles showed decreased
      myofibrillic adenosine triphosphatase activity indicating depressed
      contractility. This was associated with depressed oxidative activity of the
      muscle fibres. A shift to more glycolytic metabolism was observed, mainly in FG
      fibres of proximal muscle. We found an increased NOS II expression in both
      myopathic muscle types investigated. It means that increased NO production
      inhibits force generation in myopathic muscle. NOS II immunoreactivity was found
      mainly in the cytoplasm of FG fibres. NOS I and NOS III expression was not
      significantly effected by this form of myopathy. Our findings demonstrate that
      muscle fibres of proximal and distal skeletal muscles of 100-day-old
      cardiomyopathic BIO TO-2 hamsters are altered with respect to contractility,
      metabolism and NOS II expression. FG fibres of the proximal muscle were effected
      most strongly.

PMID- 11993847
TI  - Postnatal development of neurons expressing NADPH-diaphorase and parvalbumin in
      the parietal cortex of male and female rats.
AB  - Expression of the enzyme nicotinamide adenine dinucleotide phosphate-diaphorase
      (NADPH-d) and the calcium-binding protein parvalbumin was studied in the parietal
      cortex of male and female rats during postnatal development at 20, 60 and 90 days
      of age. First, localization of the activity of NADPH-d was combined with the
      immunohistochemical localization of parvalbumin to facilitate recognition of
      morphological details and distribution patterns of these two types of cortical
      neurons. Double staining of neurons for parvalbumin and NADPH-d was never found.
      Second, it was found that NADPH-d is a simple and proper marker for quantitative
      studies. Morphometric analysis revealed sexual dimorphism in the density of NADPH
      d-positive neurons in 20 days-old prepubertal rats. Females showed higher amounts
      of NADPH-d-positive neurons than males. No sex-dependent differences were
      detected in 60 days-old pubertal and 90 days-old postpubertal rats. The present
      results suggest that sex differences in the number of NADPH-d-positive neurons in
      the rat parietal cortex may be related to epigenetic effects of gonadal hormones
      in the early prepubertal period of postnatal development.

PMID- 11993848
TI  - Ultrastructural localization of xanthine oxidoreductase activity in isolated rat
      liver cells.
AB  - Xanthine oxidoreductase (XOR) can exist in a dehydrogenase form (XD) and an
      oxidase form (XO). The D-form uses NAD as cofactor and the O-form uses oxygen as
      second substrate and produces oxygen radicals. Both enzymes have a high affinity
      for hypoxanthine and xanthine as substrate and produce uric acid, a potent
      antioxidant. In the present study, XOR activity was demonstrated with the
      ferricyanide method in permeabilized isolated rat liver cells at the electron
      microscopical level. Moreover, ultrastructural localization of XO activity in
      these cells was studied with the cerium salt method. Activity of both XOR and XO
      was found in matrix and core of peroxisomes of rat liver parenchymal cells. Only
      XOR activity was present as well in the cytoplasm of rat liver parenchymal cells.
      In Kupffer cells and sinusoidal endothelial cells, XOR activity was demonstrated
      in vesicles and occasionally on granular endoplasmic reticulum. XO activity was
      not found in Kupffer cells and sinusoidal endothelial cells. The presence of uric
      acid oxidase activity in matrix and core of peroxisomes as was found previously
      suggests further breakdown of purines to allantoin in peroxisomes. It is
      suggested that the major function of XOR activity in the cytoplasm of rat liver
      parenchymal cells and in sinusoidal cells is not the production of oxygen
      radicals, but rather the production of uric acid which can act as a potent
      antioxidant.

PMID- 11993849
TI  - The specificity of the histochemical NADPH diaphorase reaction for nitric oxide
      synthase-1 in skeletal muscles is increased in the presence of urea.
AB  - Nitric oxide synthase-1 (NOS-1) can be demonstrated in the sarcolemma region of
      myofibers in rodent skeletal muscles with the use of NADPH diaphorase
      histochemistry. Since other, especially intrafibrar enzymes also exhibit NADPH
      diaphorase activity, we tried to increase the specificity of the histochemical
      reaction for NOS-1. A qualitative and quantitative analysis was performed on
      cryostat sections of fast-twitch oxidative myofiber-rich tongue and fast-twitch
      glycolytic myofibers-rich tibialis anterior muscle derived from C57 mice and NOS
      1 deficient knockout mice. All myofibers of both C57 mice and NOS-1 knockout mice
      contained significant intrafibrar NADPH diaphorase activity which was inhibited
      to almost background levels when 2 M urea was added to the incubation medium. On
      the other hand, myofibers of C57 mice but not of NOS-1-deficient knockout mice
      exhibited NADPH diaphorase activity in their sarcolemma region which was only
      weakly reduced in the presence of 2 M urea as was demonstrated by image analysis.
      Quantitative data on the activity of NADPH diaphorase(s) were obtained in situ by
      photometric analysis of formazan extracted from cryostat sections. The catalytic
      activity in tongue and tibialis anterior muscle was reduced in presence of 2 M
      urea to approximately 27% in C57 mice and to 7-17% in NOS-1 knockout mice,
      respectively. An in vitro NADPH diaphorase assay performed on homogenates of
      skeletal muscles also revealed an inhibitory effect of 2 M urea in both mouse
      strains and, additionally, indicated an upregulation of NADPH diaphorase activity
      in NOS-1 knockout mice. Finally, an immunodepletion analysis demonstrated that
      NOS-1 comprises 38% of the total NADPH diaphorase activity in tongue and
      approximately 59% in tibialis anterior muscle in C57 mice. In conclusion, we
      recommend the addition of 2 M urea to the incubation medium to increase the
      specificity of the NADPH diaphorase reaction to localise NOS-1 with the use of
      catalytic histochemistry.

PMID- 11993850
TI  - Leydig cells of the human testis possess astrocyte and oligodendrocyte marker
      molecules.
AB  - It has been established, that Leydig cells of the human testis possess
      neuroendocrine properties and are therefore a member of the diffuse
      neuroendocrine (paraneuron) system. In the present study, we examined whether
      Leydig cells of adult (51-86 year of age) and developing (between the 15th and
      36th week of gestation) human testes are immunopositive for glial cell-specific
      antigens such as glial fibrillary acidic protein (GFAP), galactocerebroside
      (GalC), cyclic 2',3'-nucleotide-3'-phosphodiesterase (CNPase), A2B5-antigen
      (A2B5) and O4-antigen (O4). With the use of Western blots and dot blot analyses,
      respectively, GFAP, CNPase, GalC, A2B5 and O4 were found in whole testes and
      Leydig cell protein extracts of adult men. Corresponding immunohistochemical
      studies revealed presence of these antigens in the cytoplasm of Leydig cells both
      of adult testes and testes during prenatal development. Some differences in
      staining intensity of single antigens were observed probably depending on the
      functional and/or developmental stage of the single cells. In addition, GFAP-,
      GalC- and CNPase-immunopositivity was found in numerous Sertoli cells of the
      seminiferous tubules. Moreover, some connective tissue cells (compartmentalizing
      cells or Co-cells) of the intertubular space showed immunopositivity for CNPase,
      A2B5 and GalC. The results obtained show that Leydig cells of the human testis,
      in addition to their endocrine, neuronal and neuroendocrine features, possess
      qualities of both astrocytes and oligodendrocytes and thus show qualities of
      multipotential cells. Leydig cells probably differentiate to a phenotype that is
      characteristic for cells in the developing nervous system. Furthermore, the
      established immunohistochemical similarities are consistent with the assumption
      that foetal and postnatal Leydig cells are of common origin.

PMID- 11993851
TI  - Extracellular pH modulates the secretion of fibronectin isoforms by human
      trophoblast.
AB  - Differentiation of human trophoblast from the proliferative to the invasive
      phenotype takes place in a hypoxic and thus likely an acidic microenvironment.
      During differentiation, the secretion pattern of fibronectin isoforms changes.
      Therefore, we analysed the relation between extracellular pH, secretion of
      fibronectin splice variants and invasiveness. By means of immunohistochemistry
      and biochemistry, cellular non-oncofetal fibronectins were found in placental
      stroma and around extravillous trophoblast, whereas oncofetal isoforms only
      marked the extracellular matrix of extravillous trophoblast. In vitro,
      mesenchymal cells produced non-oncofetal fibronectins only, whereas
      choriocarcinoma cell lines, extravillous trophoblast and
      choriocarcinoma/trophoblast hybrid cells secreted both non-oncofetal and
      oncofetal isoforms. When the pH of the culture medium was either lowered or
      increased (between 6.0 and 8.0), the trophoblast hybrids, but not choriocarcinoma
      and mesenchymal cells, responded with increased secretion of fibronectins and a
      shift towards oncofetal isoforms. These changes were preserved after pH
      normalisation. Histochemical determination of local tissue acidity revealed that
      the site of the lowest detectable tissue pK coincided with the starting point of
      invasion, the proximal part of trophoblastic cell columns. Therefore, it is
      concluded that the local pH plays an important role as regulator of
      differentiation of human trophoblast as reflected by the synthesis of oncofetal
      fibronectins by the invasive phenotype of extravillous trophoblast.

PMID- 11993852
TI  - Adrenomedullin in mammalian and human skin glands including the mammary gland.
AB  - Adrenomedullin is a peptide that has been ascribed numerous functions. In the
      present paper, adrenomedullin has been localized immunhistochemically in a
      variety of skin glands of humans, elephants and impalas: apocrine scent glands,
      eccrine sweat glands, holocrine glands and mammary glands. In the apocrine glands
      expression of adrenomedullin varied with respect to staining intensity and
      intracellular localization. In general, glands which appeared to be actively
      secreting were more strongly stained than quiescent glands. However, within a
      single glandular tubule, individual cells differed considerably in the staining
      intensity of adrenomedullin. Adrenomedullin was present in both non-lactating and
      lactating mammary secretory epithelia, both ducts and alveoli reacted positively.
      In human mammary glands displaying apocrine metaplasia, the apical protrusions
      were strongly positive. Furthermore, positive immunostaining was found in
      endothelium and often in smooth muscle cells of small arteries and veins and in
      mast cells as well. Many of the adrenomedullin-positive epithelial cells were
      most strongly stained in the area of the Golgi apparatus, the cellular apex and
      particularly close to the basal side of the cell membrane. This pattern suggests
      packaging of adrenomedullin into secretory granules and secretion both at the
      apex of cells and at their basis. The first form of secretion suggests exocrine
      secretion, the latter form endocrine secretion of adrenomedullin. A possible
      hormonal function is in line with basally located electron dense small secretory
      granules, which have been found by electron microscopy in the glandular epithelia
      studied.

PMID- 11993853
TI  - PCNA in the ovary of zebrafish (Brachydanio rerio, Ham.-Buch.).
AB  - PCNA, a nuclear protein intimately involved in DNA synthesis, has been localized
      immunohistochemically in ovaries of zebrafish (Brachydanio rerio, Ham.-Buch.).
      Positively stained cells were detected in the follicle epithelium of all stages
      of growing oocytes and degenerating oocytes. Furthermore, PCNA was found to be
      present in nuclei of oogonia and oocytes in meiotic prophase. Follicle epithelium
      showed an increasing number of PCNA-positive cells during egg cell development
      with a very low index of <0.5% at the beginning and a maximum of >7% in stage IV
      oocytes that are rapidly incorporating yolk protein. In this phase, follicle
      epithelium often showed groups of stained cells in limited zones of
      proliferation. In degenerating oocytes, over 60% of the former follicle cells
      were positive for PCNA. Nuclei of oogonia were always positive and the nucleus of
      stage III oocytes showed strong positivity. Stage III is the stage in which
      amplification of rRNA genes occurs and numerous nucleoli apear in the peripheral
      caryoplasm. It is concluded that PCNA expression is related to amplification of
      rDNA.

PMID- 11993854
TI  - Lectin histochemistry of the rat lymph node: visualisation of stroma, blood
      vessels, sinuses, and macrophages. A contribution to the concept of an immune
      accessory role of sinus-lining endothelia.
AB  - The lectin Chelidonium majus agglutinin (CMA) was previously shown to visualise
      endothelia of all blood vessels and those lining sinuses of red pulp, stromal
      reticular meshwok (RM) and dendritic cells of lymphatic follicles in white pulp
      of the spleen in rats. The aim of the present study was the analysis of CMA and
      some other lectins in labelling RM, vascular structures and macrophages in lymph
      nodes of rats. It appeared that CMA stained the entire RM, dendritic cells,
      lining cells of sinuses and all types of blood vessels. Sinus-lining cells of
      lymph nodes were labelled with CMA and mannose-, GalNac-, and sialic acid
      specific lectins. Moreover, lymph node macrophages were labelled above all by
      mannose specific lectins. The broad lectin-binding pattern of sinuses--not
      observed in rat spleen- and CMA-reactivity of both sinus-lining and dendritic
      cells corroborates the hypothesis that lymph node sinus-lining endothelia are
      precursors or a special type of immune accessory cells.

PMID- 11993855
TI  - Histone H1-mediated transfection: role of calcium in the cellular uptake and
      intracellular fate of H1-DNA complexes.
AB  - Previously, we have shown that the transgene expression in the endothelial cell
      line ECV 304 strongly depends on the presence of low concentrations of Ca2+.
      However, it remained unclear, which transfection steps are controlled by Ca2+
      ions. In the present study, we constructed transfection complexes of digoxigenin
      labelled DNA and FITC-labelled histone H1. We monitored the pathway of these
      complexes with the use of anti-digoxigenin and anti-cathepsin B antibodies and
      immunofluorescence microscopy. Double labelling of DNA and cathepsin B permitted
      the localization of transfection complexes into endosomes/lysosomes which
      suggests an uptake of transfection complexes via endocytosis. It was also found
      that the uptake of transfection complexes by the cells was independent of the
      presence or absence of Ca2+ ions in the transfection medium. On the other hand,
      the presence of Ca2+ in the transfection medium dramatically changed the
      composition of the transfection complexes inside the endosome/lysosome
      compartment, which resulted in a strong reduction of H1 binding to DNA. Presence
      of Ca2+ in the postincubation medium for 24 h resulted in release of the
      transfection complexes with reduced H1 content from the endosomes/lysosomes into
      the cytosol. In the absence of Ca2+ the transfection complexes practically
      disappeared. These results allow us to come to the following conclusions: Ca2+
      ions control the reorganization of the transfection complexes in
      endosomes/lysosomes and their release into the cytosol, which is an important
      prerequisite for transgene expression, whereas uptake of transfection complexes
      by the cells is not dependent on Ca2+.

PMID- 11993856
TI  - Effects of melatonin on Leydig cells in pinealectomized rat: an
      immunohistochemical study.
AB  - We have investigated immunohistochemically the effects of melatonin on Leydig
      cells in rat. Three groups of Wistar rats were used. Rats in group I and II were
      sham-pinealectomized (control) and pinealectomized, respectively, whereas rats in
      group III were pinealectomized and injected daily with melatonin for 2 months. At
      the end of the experiment, all animals were killed by decapitation and blood
      samples were obtained. Serum testosterone levels were determined with the use of
      a chemiluminescent enzyme immunoassay. Testicular tissue was collected and
      processed for semiquantitative evaluation of immunohistochemical testosterone
      staining. Intensity of immunostaining was determined on a scale between 0 (no
      staining) and 5 (heavy staining). In pinealectomized rats, serum testosterone
      levels were significantly increased as compared to sham-pinealectomized rats.
      Daily administration of melatonin after pinealectomy resulted in significant
      decreased serum testosterone levels as compared to levels in control and
      pinealectomized rats. Immunostaining of testosterone was moderate (3+) in sham
      pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in
      pinealectomized rats that were treated with melatonin, respectively. The results
      of our study indicate that pinealectomy induces increased testosterone secretion
      in Leydig cells and this increased secretion can be prevented by administration
      of melatonin.

PMID- 11993857
TI  - Analysis of surface properties of fixed and live cells using derivatized agarose
      beads.
AB  - A novel assay has been developed for the histochemical characterization of
      surface properties of cells based on their adhesion to agarose beads derivatized
      with more than 100 types of molecules, including sugars, lectins and other
      proteins, and amino acids. The assay simply involves mixing small quantities of
      washed cells and beads in droplets on glass microscope slides and determining to
      which beads various cell types adhere. Distilled water was found to be the best
      medium for this assay because added ions or molecules in other media inhibit
      adhesion in some cases. Many cells, however, cannot tolerate distilled water.
      Here we show that cells fixed with either of two fixatives (1% formaldehyde or
      Prefer fixative) displayed similar bead-binding properties as did live cells.
      Specificity of cell-bead binding was tested by including specific free molecules
      in the test suspensions in hapten-type inhibition experiments. If a hapten
      compound inhibited live-cell adhesion to a specific bead, it also inhibited fixed
      cell adhesion to a specific bead. The results of these experiments suggest that
      fixed cells display authentic surface properties, opening the door for the use of
      this assay with many cell types that cannot tolerate distilled water.

PMID- 11993858
TI  - Integrating pollution prevention technology into public policy: the case of
      professional wet cleaning.
AB  - This paper discusses opportunities to promote pollution prevention technologies
      through public policy, describing the case of dry cleaning. The crisis in dry
      cleaning is associated with the industry's reliance on perchloroethylene (PCE),
      the chemical cleaning solvent used by the vast majority of cleaners. The limits
      to the current pollution control or end-of-pipe system of laws and regulations
      and the search for nontoxic alternatives are analyzed in light of the
      environmental and occupational hazards associated with PCE use. Criteria to
      evaluate those alternatives are then described, including their application to
      professional wet cleaning, a commercially available pollution prevention
      alternative to PCE. The article concludes with an evaluation of several public
      policy instruments that could be used to promote the diffusion of professional
      wet cleaning as a potential solution to this regulatory crisis. These include
      environmental and occupational regulations designed to reduce or eliminate risk
      from exposure to toxic substances as well as incentive-based programs. Both
      barriers and opportunities for the use of each instrument are identified. This
      review reveals that, while the pollution control approach to public policy has
      deepened the regulatory crisis in the garment care industry, policy instruments
      are currently available to create an effective transition toward a pollution
      prevention outcome.

PMID- 11993859
TI  - Emissions of aldehydes and ketones from a two-stroke engine using ethanol and
      ethanol-blended gasoline as fuel.
AB  - Besides aliphatic gasoline, ethanol-blended gasoline intended for use in small
      utility engines was recently introduced on the Swedish market. For small utility
      engines, little data is available showing the effects of these fuels on exhaust
      emissions, especially concerning aldehydes and ketones (carbonyls). The objective
      of the present investigation was to study carbonyl emissions and regulated
      emissions from a two-stroke chain saw engine using ethanol, gasoline, and ethanol
      blended gasoline as fuel (0%, 15%, 50%, 85%, and 100% ethanol). The effects of
      the ethanol-blending level and mechanical changes of the relative air/fuel ratio,
      lambda, on exhaust emissions was investigated, both for aliphatic and regular
      gasoline. Formaldehyde, acetaldehyde, and aromatic aldehydes were the most
      abundant carbonyls in the exhaust. Acetaldehyde dominated for all ethanol-blended
      fuels (1.2-12 g/kWh, depending on the fuel and lambda), and formaldehyde
      dominated for gasoline (0.74-2.3 g/kWh, depending on the type of gasoline and
      lambda). The main effects of ethanol blending were increased acetaldehyde
      emissions (30-44 times for pure ethanol), reduced emissions of all other
      carbonyls exceptformaldehyde and acrolein (which showed a more complex relation
      to the ethanol content), reduced carbon monoxide (CO) and ntirogen oxide (NO)
      emissions, and increased hydrocarbon (HC) and nitrogen dixodie (NO2) emissions.
      The main effects of increasing lambda were increased emissions of carbonyls and
      nitrogen oxides (NOx) and reduced CO and HC emissions. When the two types of
      gasoline are considered, benzaldehyde and tolualdehyde could be directly related
      to the gasoline content of aromatics or olefins, but also acrolein, propanal,
      crotonaldehyde, and methyl ethyl ketone mainly originated from aromatics or
      olefins, while the main source for formaldehyde, acetaldehyde, acetone,
      methacrolein, and butanal was saturated aliphatic hydrocarbons.

PMID- 11993860
TI  - Episodes of elevated methylmercury concentrations in prairie streams.
AB  - Methylmercury (MeHg) and total mercury (THg) concentrations were determined
      weekly from late March through mid-December 2000 in unfiltered water samples from
      two prairie streams in south-central Minnesota. The Little Cobb River and County
      Ditch 86 drain predominantly agricultural watersheds, but riparian areas along
      much of the Little Cobb River are forested, whereas County Ditch 86 is a
      utilitarian drainage waterway with grassed riparian areas. Episodes of elevated
      MeHg concentration (1.3 ng/L) were observed in both streams in early May during a
      period of algal bloom. Between late May and late September, MeHg concentrations
      varied between 0.05 and 0.39 ng/L in the Little Cobb River and between 0.03 and
      0.29 ng/L in County Ditch 86. Precipitation was well below average in August and
      September, and discharge in both streams ceased by late September. MeHg
      concentrations in the Little Cobb River increased dramatically in early October
      after autumnal leaf fall, increasing from 0.44 to 4.90 ng/L over a 5-week period.
      In contrast, MeHg concentrations in County Ditch 86 varied between 0.22 and 0.48
      ng/L over the same time frame. The observed differences are thoughtto reflect
      differences in the amounts of litterfall entering the two streams. These results
      show that algal bloom and leaf fall events can result in elevated MeHg
      concentrations in surface waters, potentially leading to increased MeHg
      accumulation in fish.

PMID- 11993861
TI  - Discrimination of aerial deposition sources of polychlorinated dibenzo-p-dioxin
      and polychlorinated dibenzofuran downwind from a pulp mill near Ketchikan,
      Alaska.
AB  - Drinking water is supplied by individual roof-catchment systems for homes and
      businesses near a dissolving sulfite pulp mill (now closed) located just north of
      Ketchikan in southeast Alaska. This study was conducted to determine if
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/Fs)
      found in the sediments of the roof-catchment cisterns resulted from historical
      deposition of stack emissions from the pulp mill's multi-fuel power boilers. Fly
      ash from the power boilers had maximum total PCDD/F concentrations of 3.08 x
      10(5)-3.10 x 10(6) ng/kg, which resulted from combustion of bleach plant
      wastewater sludge and saltwater-soaked wood waste. Cistern sediments had maximum
      total PCDD/F concentrations of 7.71 x 10(4) ng/kg. Potential sources of PCDDs/Fs
      in the cistern sediments were considered to be automobile exhaust, heating oil
      combustion, and private trash burning as well as pulp mill boiler emissions.
      Discriminant analysis was used to analyze differences between profiles of tetra
      through octa homologue classes of PCDDs/ Fs (defined as proportional
      contributions to total concentration) from different source terms. Homologue
      profiles of potential sources from Ketchikan included in this analysis were fly
      ash collected from the mill's power boilers and soils collected from background
      areas (areas with similar PCDD/F sources as the residences [e.g., auto exhaust
      and burn barrels] near the mill but beyond the zone of aerial deposition of
      emissions from the mill). Profiles for emissions from automobile exhaust,
      fertilizers, oil heating, residential trash burning, and residential wood heating
      were also included in the source "training" data set (for the discriminant
      analysis) using data from published literature. The classification rules
      developed from the discriminant analysis were applied to the following test media
      sampled at Ketchikan: roof-catchment cistern sediments and soils collected from
      areas in the vicinity of the mill's power boilers (i.e., nearby residential or
      commercial [developed] areas, on the mill property, and nearby forestlands). The
      homologue profiles of cistern sediment and nearby developed area soil samples
      were similar to background soils, whereas the profiles for the forestland soil
      samples (influenced by emissions from the mill but not other anthropogenic
      sources) closely matched the fly ash pattern. The homologue profiles of the
      emission sources from published data were more similar to one another than either
      background soils or fly ash. Soil samples from the mill property were classified
      as members of all source groups. On the basis of these analyses, the composition
      of PCDDs/Fs detected in the cistern sediments is typical of Ketchikan background
      conditions and not reflective of mill emissions.

PMID- 11993862
TI  - Endocrine disrupting nonylphenols are ubiquitous in food.
AB  - 4-Nonylphenols (NPs) are common products of biodegradation of a widely used group
      of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are
      known to be persistent, toxic, and estrogen active. There is a worldwide
      scientific and public discussion on the potential consequences of human long term
      dietary exposure to such endocrine disrupters. Despite numerous determinations of
      NPs in environmental samples no systematical reports exist relating to
      concentrations of NPs in food. We analyzed NPs in 60 different foodstuff
      commercially available in Germany. The results indicate that NPs are ubiquitous
      in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and
      19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on
      German food consumption rates and these first analyses of NPs in food, the daily
      intake for an adult was calculated to be 7.5 microg/day NPs. For infants
      exclusively fed with breast milk or infant formulas daily intakes of 0.2
      microg/day and 1.4 microg/day NPs, respectively, can be estimated.

PMID- 11993863
TI  - Quantitative characterization of trace levels of PFOS and PFOA in the Tennessee
      River.
AB  - Although there is evidence of widespread distribution of organic fluorochemicals
      such as perfluorooctane sulfonate and perfluorooctanoate, in the environment, the
      versatility of these compounds in industrial and commercial applications
      complicates characterization of pathways into the environment. A solid-phase
      extraction method coupled with HPLC-negative-ion electrospray tandem mass
      spectrometry was developed to quantitatively measure trace levels of organic
      fluorochemicals in drinking water and surface water. Using this method, certain
      fluorochemicals can be quantitatively measured in water samples down to 25 ppt, a
      level well below calculated drinking water advisory levels. To assess
      fluorochemical distribution in a localized geography and to ascertain whether
      fluorochemical manufacturing facilities contribute to environmental levels of
      fluorochemicals, 40 water samples were collected on an 80-mi stretch of the
      Tennessee River, near a fluorochemical manufacturing site in Decatur, AL. Low
      levels (ppt) of perfluorooctane sulfonate were determined throughout the stretch
      of river sampled. Concentrations of the measured fluorochemicals increased
      downstream of the fluorochemical manufacturing facility, indicating that effluent
      from manufacturing is one likely source of organic fluorochemicals into the
      river.

PMID- 11993864
TI  - Effects of biodiesel blends and Arco EC-diesel on emissions from light heavy-duty
      diesel vehicles.
AB  - Chassis dynamometer tests were performed on seven light heavy-duty diesel trucks
      comparing the emissions of a California diesel fuel with emissions from four
      other fuels: ARCO emissions control diesel (EC-D) and three 20% biodiesel blends
      (one yellow grease and two soy-based). The EC-D and the yellow grease biodiesel
      blend both showed significant reductions in total hydrocarbons (THC) and carbon
      monoxide (CO) emissions over the test vehicle fleet. EC-D also showed reductions
      in particulate matter (PM) emission rates. NOx emissions were comparable for the
      different fuel types for most of the vehicles tested. The soy-based biodiesel
      blends showed smaller emissions differences over the test vehicles, including
      some increases in PM emissions. This is somewhat in contrast to previous studies
      that have shown larger reductions in THC, CO, and PM for biodiesel blends. The
      possible influence of different fuels, fuel properties, and engine load on
      emissions is also discussed.

PMID- 11993865
TI  - Comparison of trihalomethanes in tap water and blood.
AB  - Trihalomethane (THM) concentrations in blood and tap water were measured for 50
      women living in two locations with different bromide concentrations and
      disinfectant types. Blood samples were taken from each woman early in the morning
      prior to any major water-use activity and again immediately after showering. Each
      residence was sampled for THMs in tap water prior to the woman's shower. Cobb
      County, GA, tap water exhibited high THM concentrations composed primarily of
      chloroform. Corpus Christi, TX, tap water exhibited lower THM concentrations with
      significant proportions of brominated THMs. THMs in tap water and blood were
      compared using mole fraction speciation, extent of bromine incorporation, and
      correlation analysis. Results indicated that THMs in the blood rose significantly
      as a result of showering, that showering shifted the THM distribution in the
      blood toward that found in the corresponding tap water, and that THMs measured in
      the blood of women living in the two locations reflected species and
      concentration differences in their respective tap waters. In general, blood
      concentrations were not significantly correlated with tap water concentrations.
      This finding suggests that other factors, in addition to tap water
      concentrations, may be important in determining THM concentrations in the blood.

PMID- 11993866
TI  - Transport of humic and fulvic acids in relation to metal mobility in a copper
      contaminated acid sandy soil.
AB  - The transport of inorganic and organic pollutants in water and soil can be
      strongly influenced by the mobility of natural dissolved organic matter (DOM). In
      this paper, the transport of a humic acid (HA) and a fulvic acid (FA) in a copper
      contaminated acid sandy soil was studied. The data showed that the transport
      behavior of HA differed from that of FA. The breakthrough curves (BTCs) of HA
      were characterized by a rapid relatively sharp front followed by a plateau at a
      lower HA concentration than in the influent solution. The increase of the Ca
      concentration decreased the HA concentration further. Compared to HA, the BTCs of
      FA were retarded and showed an extended tailing, approaching complete
      breakthrough. The increase of the Ca concentration decreased the FA concentration
      only temporarily. On the basis of our model calculation, the characterization of
      HA transport could be explained by the coagulation of HA largely upon the binding
      of Al. The increase of the Ca concentration resulted in further coagulation of HA
      because of the increased Ca adsorption, which occurred mainly in the Donnan
      phase. For FA, the adsorption to the soil matrix was more likely the process that
      controls its solubility and mobility. The mobility of Al and Cu in the soil
      column was closely related to the solubility and transport of the DOM in soil
      solution. The concentration of Ca in the effluent was lower than in the influent
      because Ca was retained in the soil due to the retardation of HA and FA and due
      to the compensation of the other cations released from the soil to the solution.

PMID- 11993867
TI  - Reductive dissolution and biomineralization of iron hydroxide under dynamic flow
      conditions.
AB  - Iron cycling and the associated changes in solid phase have dramatic implications
      for trace element mobility and bioavailability. Here we explore the formation of
      secondary iron phases during microbially mediated reductive dissolution of
      ferrihydrite-coated sand under dynamic flow conditions. An initial period (10 d)
      of rapid reduction, indicated by consumption of lactate and production of acetate
      and Fe-(II) to the pore water in association with a darkening of the column
      material, is followed by much lower rate of reduction to the termination of the
      experiment after 48 d. Although some Fe (<25%) is lost to the effluent pore
      water, the majority remains within the column as ferrihydrite (20-70%) and the
      secondary mineral phases magnetite (0-70%) and goethite (0-25%). Ferrihydrite
      converts to goethite in the influent end of the column where dissolved Fe(II)
      concentrations are low and converts to magnetite toward the effluent end where
      Fe(III) concentrations are elevated. A decline in the rate of Fe(II) production
      occurs concurrent with the formation of goethite and magnetite; at the
      termination of the experiment, the rate of reduction is <5% the initial rate.
      Despite the dramatic decrease in the rate of reduction, greater than 80% of the
      residual Fe remains in the ferric state. These results highlight the importance
      of coupled flow and water chemistry in controlling the rate and solid-phase
      products of iron (hydr)oxide reduction.

PMID- 11993868
TI  - Scavenging of As from acid mine drainage by schwertmannite and ferrihydrite: a
      comparison with synthetic analogues.
AB  - Ochreous precipitates containing 5.5-69.8 g/kg As were isolated from mine
      drainage in Finland and were composed of schwertmannite, ferrihydrite, and
      goethite. Schwertmannite formation was favored at pH 3-4, but its structure was
      degraded at high As levels. A series of coprecipitates were therefore prepared
      from mixed iron arsenate/sulfate solutions to define the limits of schwertmannite
      stability. Schwertmannite was replaced as the dominant phase by a poorly
      crystalline ironIII hydroxy arsenate (FeOHAs) when As/Fe mole ratios exceeded
      0.15. The FeOHAs gave an X-ray diffraction pattern similar to that obtained from
      an "amorphous" ironIII arsenate (As/Fe = 1.0) with broad peaks at 0.30 and 0.16
      nm. The FeOHAs possessed a magnetic hyperfinefield of 41.9T at 4.2 K that was
      intermediate to those of schwertmannite (46.1 T) and the ironIII arsenate (24.8
      T). These data indicate a strong disruptive effect of arsenate on magnetic
      ordering and structure development in schwertmannite. Equilibration of 0.01 M
      arsenate solutions with freshly prepared schwertmannite and 2-line ferrihydrite
      at pH 3.0 for up to 60 d gave sorbed As contents of 175 and 210 g/kg,
      respectively. Arsenate sorption degraded the host schwertmannite and
      ferrihydrite, perhaps due to the formation of an FeOHAs surface phase.

PMID- 11993869
TI  - Anaerobic electrochemical corrosion of mild steel in the presence of
      extracellular polymeric substances produced by a culture enriched in sulfate
      reducing bacteria.
AB  - The corrosion of mild steel in a seawater medium containing extracellular
      polymeric substances (EPS) produced by sulfate-reducing bacteria (SRB) was
      studied by electrochemical experiments and atomic force microscopy (AFM). Under
      anaerobic conditions, the corrosion of mild steel increased up to 5-fold in the
      presence of a 1% (w/w) EPS solution but in the absence of SRB. The enhanced
      corrosion is mainly due to the oxidizing power of EPS with a reduction potential
      of E1/2 at -0.54 V (saturated calomel electrode), which is 0.4 V above that of
      hydrogen reduction. The electrochemical reduction of EPS provides a couple to
      iron oxidation, as demonstrated by H-shaped cell experiments in which the steel
      sample and EPS are not in physical contact but are ionically connected via the
      solution and electronically connected through an external wire. Fourier
      transformation infrared spectroscopy and X-ray photoelectron spectroscopy showed
      that EPS derived from SRB are comprised of 60% proteins, 37% polysaccharides, and
      3% hydrocarbons. The XPS results showed that, upon corrosion, polysaccharide
      components were mostly converted to hydrocarbons.

PMID- 11993870
TI  - Spectroscopic study of copper(II)--wheat straw cell wall residue surface
      complexes.
AB  - The sorption of copper(II) by wheat straw cell wall residue (CWR) was studied and
      revealed a relatively stable surface complexation on the acid sites of the
      substrate (carboxylic and phenolic moieties). The copper binding capacity at pH =
      5.75 and ionic strength of 0.1 M was evaluated at 63 micromol x g(-1) CWR. The
      Langmuir and Freundlich isotherm equations were then used to describe the
      partitioning behavior for the system at different pH values. Batch experiments
      have been achieved in the presence of calcium in order to mimic the calcareous
      soil of the Champagne region. A competitive effect on copper complexation has
      been shown, which is presumably due to the calcium ability to form outer-sphere
      complexes far less stable than copper(II) ones. Electron spin resonance and X-ray
      absorption spectroscopy were combined to obtain information on the geometry and
      structure of Cu bound to CWR. At least two different binding sites for Cu2+ were
      found to take place in CWR. From ESR parameters, we deduced that copper(II) ions,
      when complexed with CWR, are coordinated in a square-planar arrangement with four
      oxygen-containing groups. EXAFS and XANES experiments revealed that Cu(II) is
      surrounded by four oxygen atoms, with an average Cu-O equatorial distance equal
      to 1.94 A.

PMID- 11993871
TI  - Reduction of polyhalogenated methanes by surface-bound Fe(II) in aqueous
      suspensions of iron oxides.
AB  - Uptake of ferrous iron from aqueous solution by iron oxides results in the
      formation of a variety of reactive surface species capable of reducing
      polyhalogenated methanes (PHMs). Pseudo-first-order reaction rate constants,
      k(obs), of PHMs increased in the order CHBrCl2 < CHBr2Cl < CHBr3 < CCl4 < CFBr3 <
      CBrCl3 < CBr2Cl2. The k(obs) values increased with the exposure time, teq, of
      Fe(II) to suspended iron oxides which was attributed to the rearrangement of
      initially sorbed Fe(II) species to more reactive surface species with time. At pH
      7.2, the k(obs) values of PHMs also increased with the concentration of surface
      bound ferrous iron, Fe(II)sorb, particularly when Fe(II)tot was increased to
      concentrations where surface precipitation becomes likely. At fixed total Fe(II)
      concentrations, k(obs) values increased exponentially with pH. The highest
      reactivities were associated with pH conditions where surface precipitation of
      Fe(II) is expected. Fe(II)sorb and pH, however, had opposite effects on the
      product formation of PHMs. At pH 7.2, the formation of formate from CX4 (X = CI,
      Br) increased with Fe(II)sorb, whereas increasing pH favored the formation of
      CHX3. The ratio of halogenated products and formate formed is indicative of the
      relative importance of initial one- or two-electron-transfer processes,
      respectively, and was found to depend on the type of iron oxide mineral also. Our
      data form a basis to assess the importance of chemical reactions in natural
      attenuation processes of PHMs in environmental systems under iron-reducing
      conditions.

PMID- 11993872
TI  - Zinc speciation in a smelter-contaminated soil profile using bulk and
      microspectroscopic techniques.
AB  - A soil profile contaminated as a result of Zn smelting operations from the
      historic Palmerton, PA smelting facility was characterized using X-ray absorption
      fine structure spectroscopy (XAFS) and X-ray diffraction (XRD) as bulk
      techniques, coupled with electron microprobe (EM), and microfocused XAFS as
      microscopic techniques to determine the chemical forms of Zn and elucidate its
      geochemical fate. The black, organic matter-rich topsoil contained 6200 mg/ kg Zn
      and was strongly acidic (pH 3.2). Bulk XAFS revealed that about 2/3 of Zn was
      bound in franklinite and 1/3 bound in sphalerite. Both minerals may have been
      aerially deposited from the smelter operation. Microspectroscopy detected also
      minor amounts of Zn adsorbed to Fe and Mn (hydr)oxides as inner-sphere sorption
      complexes, which may have formed after weathering of the Zn minerals. About 10%
      of the total Zn in this sample could be easily leached. In contrast, the
      yellowish, loamy subsoil contained less Zn (890 mg/kg) and had a higher pH of
      3.9. XAFS revealed that Zn was mostly bound to Al-groups and to a lesser extent
      to Fe and Mn (hydr)oxides. Minor amounts of outer-sphere complexes or organic
      matter-bound Zn species could also be detected. About 70% of the total Zn content
      could be easily leached, indicating that outersphere sorption complexes have been
      underestimated and/ or inner-sphere sorption complexes are weak due to the low
      pH. The Zn forms in the subsoil most likely derive from weathering of the Zn
      minerals in the topsoil. Due to the lack of minerals incorporating Zn and due to
      the low pH, the availability of Zn in the subsoil is as high as in the topsoil,
      while the total concentration is almost 1 order of magnitude smaller.

PMID- 11993873
TI  - Something from "nothing"--eight weak estrogenic chemicals combined at
      concentrations below NOECs produce significant mixture effects.
AB  - We tested whether multicomponent mixtures of xenoestrogens would produce
      significant effects when each component was combined at concentrations below its
      individual NOEC or EC01 level. The estrogenic effects of eight chemicals of
      environmental relevance, including hydroxylated PCBs, benzophenones, parabenes,
      bisphenol A, and genistein, were recorded using a recombinant yeast estrogen
      screen (YES). To ensure that no chemical contributed disproportionately to the
      overall combination effect, a mixture was prepared at a mixture ratio
      proportional to the potency of each individual component. The performance of four
      approaches for the calculation of additive combination effects (concentration
      addition, toxicity equivalency factors, effect summation, and independent action)
      was compared. Experimental testing of the predictions revealed that concentration
      addition and its application, the toxicity equivalency factor approach, were
      valid methods for the calculation of additive mixture effects. There was
      excellent agreement between prediction and observation. In contrast, independent
      action and effect summation led to clear underestimations of the experimentally
      observed responses. Crucially, there were substantial mixture effects even though
      each chemical was present at levels well below its NOEC and EC01. We conclude
      that estrogenic agents are able to act together to produce significant effects
      when combined at concentrations below their NOECs. Our results highlight the
      limitations of the traditional focus on the effects of single agents. Hazard
      assessments that ignore the possibility of joint action of estrogenic chemicals
      will almost certainly lead to significant underestimations of risk.

PMID- 11993874
TI  - Mechanisms of arsenic uptake from aqueous solution by interaction with goethite,
      lepidocrocite, mackinawite, and pyrite: an X-ray absorption spectroscopy study.
AB  - The mechanisms whereby As(III) and As(V) in aqueous solution (pH 5.5-6.5)
      interact with the surfaces of goethite, lepidocrocite, mackinawite, and pyrite
      have been investigated using As K-edge EXAFS and XANES spectroscopy. Arsenic
      species retain original oxidation states and occupy similar environments on the
      oxyhydroxide substrates, with first-shell coordination to four oxygens at 1.78 A
      for As(III) and 1.69 A for As(V). In agreement with other workers, we find that
      inner sphere complexes form, apparently involving bidentate (bridging) arsenate
      or arsenite. Interaction of As(III) and As(V) with the sulfide surfaces shows
      primary coordination to four oxygens (As-O: 1.69-1.76 A) with further sulfur
      (approximately 3.1 A) and iron (3.4-3.5 A) shells suggesting outer sphere
      complexation. Arsenic species were also coprecipitated with mackinawite (pH 4.0),
      and these samples were further studied following oxidation. At high As(III) or
      As(V) concentrations, arsenate or arsenite species form, probably as sorption
      complexes, along with poorly crystalline arsenic sulfide (the only product at low
      As(V) concentrations). All oxidized samples show primary coordination to four
      oxygens at 1.7 A, indicating As(V); these arsenates may show both outer sphere
      complexation with residual mackinawite and inner sphere complexation with new
      oxyhydroxides. These experiments help to clarify our understanding of As mobility
      in near-surface environments.

PMID- 11993875
TI  - Acute silver toxicity in aquatic animals is a function of sodium uptake rate.
AB  - On the basis of these facts about freshwater fish and invertebrates: (i) the Na+
      turnover is a physiological process associated with the gill membranes; (ii) the
      key mechanism of acute silver toxicity consists of reduction in Na+ uptake by
      blockade of gill Na+,K+-ATPase; (iii) the mass-specific surface area of the gills
      depends on animal body mass; and (iv) the gill surface is also the major site of
      Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e.,
      turnover rate) and secondarily body mass would be good predictors of acute silver
      toxicity. Results obtained from toxicological (LC50 of AgNO3) and physiological
      (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus
      mykiss), early juvenile and adult crayfish (Cambarusdiogenes diogenes), and
      neonate and adult daphnids (Daphnia magna) in moderately hard water of constant
      quality support the above hypothesis. Therefore, sensitivity to AgNO3, in terms
      of either total measured silver or free Ag+, was reliably predicted from the
      whole body Na+ uptake rate in animals with body mass ranging over 6 orders of
      magnitude (from micrograms to grams). A positive log-log correlation between
      acute AgNO3 toxicity and body mass of the same species was also observed.
      Furthermore, the whole body Na+ uptake rate was inversely related to body mass in
      unexposed animals. The combination of these last two results explains why the
      small animals in this study were more sensitive to Ag+ than the larger ones.
      Taken together, these results clearly point out the possibility of incorporating
      the Na+ uptake rate into the current version of the Biotic Ligand Model to
      improve the predictive capacity of this model. In the absence of information on
      Na+ uptake rate, then body mass may serve as a surrogate.

PMID- 11993876
TI  - Laboratory evaluation of a mercury CEM using atomic absorption with a deuterium
      background correction system.
AB  - A prototype mercury (Hg) analyzer based on atomic absorption (AA) with a
      broadband background correction system using a deuterium (D2) lamp was developed
      and tested in the laboratory. Initial tests were performed using a small
      commercially available AA Hg detector operated in series with an optical
      breadboard version of the D2 background correction system. Based on encouraging
      results obtained with that system while using streams of elemental Hg and SO2 (an
      interfering gas), a compact prototype Hg analyzer for use in a Hg continuous
      emission monitor (CEM) was built. In laboratorytests performed in the absence of
      interfering gases, the analyzer could detect 0.5 microg/m3 or less of elemental
      Hg. The noise in the D2 channel of the analyzer was a limiting factor with
      respect to instrument sensitivity when background-corrected absorbance values
      were used. Tests with gas streams containing 9-26 microg/m3 of elemental Hg and
      0.02-0.44% SO2 indicated that the D2 background correction approach did a good
      job at subtracting the large interfering signal due to SO2. However, a correction
      factor had to be applied to the absorbance readings from the D2 channel of the
      analyzer in order to obtain acceptable accuracy for the background-subtracted Hg
      measurements.

PMID- 11993877
TI  - An absolute calibration for gas-phase hydroxyl measurements.
AB  - We describe a new method of calibrating tropospheric hydroxyl (OH) instruments.
      Ozone-alkene mixtures produce steady-state OH radical concentrations. The steady
      state is governed by competition between OH production in the reaction of ozone
      with the alkene and OH removal by reactions with the alkene, ozone, and the
      reactor wall. In a flowtube reactor transporting an ozone-alkene mixture, the OH
      wall loss rate can be measured by varying the alkene concentration. Delivery of
      the reaction mixture to the sampling entry of an atmospheric OH measurement
      instrument provides an absolute calibration of the instrument's response to OH.
      The present precision of calibration is +/-8% (1-sigma), based on reproducibility
      over a wide range of ozone concentrations. The accuracy (+/-43%) is limited by
      uncertainties in kinetic rate coefficients and OH yield, which can be improved.
      The calibration requires no photon flux measurements or lamp-dependent absorption
      coefficients, which have inherent, variable, systematic uncertainties, and it has
      been tested in field experiments.

PMID- 11993878
TI  - Calibration and field verification of semipermeable membrane devices for
      measuring polycyclic aromatic hydrocarbons in water.
AB  - The use of semipermeable membrane devices (SPMDs) has become common in
      environmental sampling of nonpolar organic contaminants, yet few data exist for
      the uptake or sampling rates of polycyclic aromatic hydrocarbons (PAH). Two
      separate laboratory calibration experiments were conducted to determine the
      sampling rates of 28 individual PAH and 19 homologues. PAH with a log Kow > 4.5
      remained in the linear uptake phase for 30 days, but PAH with a log Kow < 4.5
      began to approach steady state within 15 days. Sampling rates, corrected for
      dissolved organic carbon, ranged from 2.11 to 6.06 L d(-1). Shear flow across the
      membrane had no statistically significant effect on rates over the range of 0.01
      0.50 cm s(-1). Field verification of these sampling rates yielded agreement
      within about a factor of 2 for most PAH and a factor of 4 for all PAH. The worst
      agreement was for the most hydrophobic PAH, where partitioning into dissolved and
      particulate organic carbon pools are more important and less certain. These SPMD
      sampling rate data will allow quantitative estimations of freely dissolved
      concentrations of 47 compounds that are commonly used for PAH and petroleum
      product source identification and allocation.

PMID- 11993879
TI  - Optimization of a mist chamber (Cofer scrubber) for sampling water-soluble
      organics in air.
AB  - While the atmospheric fate and transport of biogenic and anthropogenic
      hydrocarbons has been extensively studied, little is known about the behavior of
      first-, second-, and third generation photo-oxidation products that arise from OH
      radical oxidation of the parent species. The results of chamber experiments
      establish that *OH oxidation of biogenic and anthropogenic hydrocarbons yields
      carbonyls, dicarbonyls, hydroxycarbonyls, and keto-acids. However, little is
      known about the generation and fate of these products in the ambient atmospheric
      environment. This is changing because of the advent of methods that rely on 0
      (2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) derivatization of carbonyls in
      concert with gas chromatography/ion trap mass spectrometry. Such methods provide
      the means to identify and quantify water-soluble organics, which historically
      have been difficult to measure. A limitation of existing sampling methods,
      however, is the use of devices that require low flow rates (0.5-1 L min(-1)).
      Accordingly, long sampling times (3-4 h) are needed to obtain pptv-ppbv detection
      limits. The mist chamber is an attractive device because of the high flow rates
      (25-70 L min(-1)) compatible with its use. Herein, we evaluate a mist chamber
      using a flow rate of 25-30 L min(-1) to provide short (10 min) sampling times and
      pptv limits of detection. The results establish a relationship between the
      Henry's law constant (KH) and the collection efficiency and demonstrate the
      suitability of the method to measure analytes with KH > or = 10(3) M atm(-1).
      Adjusting the pH, adding quaternary ammonium salts, or decreasing the temperature
      of the collecting solution in the mist chamber did not significantly affect the
      collection efficiency. We tested the method by sampling photooxidation products
      of isoprene (glyoxal, methylglyoxal, hydroxyacetone, and glycolaldehyde) in the
      Blodgett Forest, CA. This is the first report of a study the employs the mist
      chamberto sample hydroxycarbonyls. The accuracy and the reproducibility of the
      method were evaluated by the analysis of duplicate samples and field spikes. The
      mean recovery of field spikes was > or =80%, and the relative standard deviation
      was < or =22% between duplicate measurements. The detection limits were 48, 15,
      7.7, and 2.7 pptv for glycolaldehyde, hydroxyacetone, methylglyoxal, and glyoxal,
      respectively. This work demonstrates the power of the mist chamber in concert
      with PFBHA derivatization and mass spectrometry to measure pptv concentrations of
      water-soluble organics with a sampling time of 10 min.

PMID- 11993880
TI  - The application of tris buffer and copper sulfate for the preservation of
      phenylurea pesticides analyzed using U.S. EPA method 532 in the UCMR Survey.
AB  - A high performance liquid chromatographic method was developed to meetthe U.S.
      Environmental Protection Agency's (EPA) Unregulated Contaminant Monitoring Rule
      (UCMR) Survey need for the analysis of phenylurea pesticides in drinking waters.
      Many of these phenylurea compounds were demonstrated to degrade rapidly in the
      presence of the residual chlorine disinfectant in drinking waters. This
      degradation was halted by the addition of a tris buffer, which was initially
      chosen to optimize the sample pH prior to extraction. Copper sulfate was found to
      prevent the regrowth of microorganisms in surface waters, which was observed upon
      dechlorination. Tris buffer provided the additional benefit of keeping the copper
      sulfate preservative in solution even in groundwater matrices that caused
      precipitation of copper in its absence. A C18 solid phase, in cartridge or disk
      form, was used to efficiently extract target compounds from the preserved
      drinking water matrices. A 21-day storage stability study, together with
      precision and accuracy studies, demonstrated thatthis method had suitable
      sensitivity, selectivity, accuracy, precision, and ruggedness for use in the
      EPA's UCMR drinking water occurrence survey.

PMID- 11993881
TI  - Relative importance of charge neutralization and precipitation on coagulation of
      Kaolin with PACI: effect of sulfate ion.
AB  - The effect of the sulfate ion on coagulation with polyaluminum chloride (PACl)
      was investigated by using an optical monitoring technique together with the
      conventional jar test procedure and electrophoretic mobility (EM) measurements.
      The effect of the SO4(2-)/Al ratio, dosage, and pH were examined in detail. The
      experimental results show that sulfate has a significantly different effect on
      PACl coagulation as a result of preformed hydrolysis products, where charge
      neutralization and precipitation play different parts in the coagulation process.
      The increased rate of coagulation with increasing SO4(2-)/Al ratio can be
      partially explained by charge neutralization effects, through increased
      adsorption and complexation of sulfate, thus giving increased particle collision
      efficiency. Different PACl samples were prepared with different values of B
      ([OH]/[Al]). For B = 0 (i.e., AlCl3) with mainly monomers, hydroxide
      precipitation tends to be accelerated in the presence of sulfate, giving
      significant turbidity removal. The high charge neutralization ability remains for
      samples with B = 1.5 and 2.0, with large proportions of preformed oligomers and
      polymers. Sulfate promotes aggregation of hydrolyzed species for B= 2.5, causing
      significantly improved coagulation efficiency through an electrostatic patch
      effect. The results illustrate further that particle charge plays a less
      important role in coagulation after reaching a certain value, while precipitate
      formation improves coagulation significantly.

PMID- 11993882
TI  - Three-ring PAH removal from waste hot gas by sorbents: influence of the sorbent
      characteristics.
AB  - Three-ring polycyclic aromatic hydrocarbons (PAH) are one of the most abundant
      PAH groups emitted during coal combustion. Four of them-acenaphthene (Ac),
      phenanthrene (Phe), fluorene (Fu), and anthracene (An)-have been listed by the
      U.S. EPA as priority pollutants. The aim in this paper is to study the abatement
      of this particular group of three-ring PAH from hot gas emissions during energy
      generation in coal combustion. The three-ring PAH adsorption capacities are
      related to the morphological and chemical properties of the 16 sorbents used in
      this work. Single and multiple linear regressions-principal component regression
      (PCR)-were applied in this study. The main conclusions reached are, first, that
      the micropore volume is the most determinant parameter for removal of these PAHs
      and, second, that the adsorption of three-ring PAH by sorbents from waste hot gas
      emissions is inversely proportional to their volatility: the lower the PAH
      volatility, the higher the adsorbent adsorption capacity. The adsorption
      isotherms show that Phe and An, both examples of PAH with three aromatic rings,
      behave similarly. However, their behavior differs from that of Ac and Fu,
      compounds in which only two of their three rings exhibit an aromatic nature.

PMID- 11993883
TI  - Isocyanate emission from PUR adhesives: influence of temperature, monomer
      content, and curing mechanism.
AB  - The isocyanate emission potential of polyurethane (PUR) adhesives was evaluated
      by measuring the area-specific emission rate (SERa;microg m(-2) h(-1)) in a
      laboratory emission test chamber. The chamber was constructed for the analysis of
      reactive substances allowing quantitative trapping of all isocyanate monomers
      emitted from the substrate. Isocyanates were analyzed as their 1-(2
      pyridyl)piperazine derivatives by HPLC with fluorescence and UV detection. The
      influence of temperature, the content of the diisocyanate in the resin, and the
      system pressure were investigated. These parameter studies gave evidence thatthe
      diisocyanate emission from the resins is a gas-phase-limited mass transfer. The
      overall mass-transfer coefficient (beta = Ddelta(-1)) was calculated for HDI and
      MDI. From the temperature dependence of emission rates, the enthalpies of
      evaporation for 2,4'-MDI, 4,4'-MDI, and HDI from their resins were determined.
      The influence of monomer content on SERa followed Henry's and Raoult's laws in
      the cases of HDI and MDI, respectively, allowing the prediction of emission rates
      proportional to diisocyanate content. Therefore, from simple parameters such as
      application temperature and monomer content, isocyanate emission rates can be
      predicted. Additionally, MDI emission from curing PUR adhesives was studied.
      These results elucidate the influence of monomer reactivity and curing mechanism
      on the decrease of MDI emission with time.

PMID- 11993884
TI  - Effect of environmental conditions on the permeability of high density
      polyethylene film to fumigant vapors.
AB  - Soil fumigation in greenhouses or agricultural fields often includes tarping the
      soil surface with polyethylene (PE) films to contain the fumigant in the soil and
      reduce emissions to the atmosphere. Previous research has demonstrated that PE
      films are permeable to methyl bromide and other fumigant compounds. In these
      experiments, the effect of temperature, fumigant mixtures, condensed water, and
      field aging on the permeability of high-density polyethylene (HDPE) was
      determined. Mass transfer coefficients (h, a measure of permeability) of the
      fumigants methyl bromide, 1,3-dichloropropene, propargyl bromide, and
      chloropicrin across HDPE films were determined. In these studies, temperature and
      HDPE film type had the largest impact on the h of fumigant compounds across HDPE
      films. Other factors investigated, including fumigant mixtures, condensed water
      on the film, and field aging of UV-stabilized film, did not have a significant
      impact on h. The results of these experiments suggest that the permeability of an
      intact piece of an agricultural film will increase with increasing temperature
      but is relatively constant despite changes in other environmental conditions.

PMID- 11993885
TI  - PCB destruction in subcritical and supercritical water--evaluation of PCDF
      formation and initial steps of degradation mechanisms.
AB  - The reduction of polychlorinated biphenyl (PCB) emissions to the environment are
      contemporary issues of global efforts, and possible destruction technologies have
      to be selected and evaluated for PCB remediation. In this study PCB destruction
      in subcritical and supercritical water were assessed under oxidative conditions
      and nonoxidative, alkaline conditions. In both cases PCBs could be destroyed by
      more than 99%. The formation of polychlorinated dibenzofurans (PCDFs) during PCB
      destruction was evaluated. Under both oxidative and nonoxidative treatments of
      sub- and supercritical conditions, the formation of PCDFs was observed. The PCDFs
      formed in the early stages of PCB destruction resulted in up to 47-fold increase
      in terms of toxic equivalency (TEQ) compared to the initial PCB mixture. However,
      the PCDFs were destroyed together with the PCBs under more severe conditions
      i.e., at higher temperature or prolonged residence time. The mechanism of PCDF
      formation and the initial step of PCB degradation was evaluated. Our laboratory
      scale investigation indicates that PCB destruction under supercritical water
      conditions is feasible, but because of the PCDF formation potential, in
      particular the high ratio of toxic 2,3,7,8-substituted congeners, conditions have
      to be carefully selected.

PMID- 11993886
TI  - Modeling of polychlorinated biphenyl removal from contaminated soil using steam.
AB  - Microwave-generated steam technology shows promise as an effective remediation
      alternative for removal of polychlorinated biphenyls (PCBs) from contaminated
      soils, based on our laboratory-scale experiments. The overall process can be
      described by a nonisothermal, unsteady, coupled heat and multicomponent PCB mass
      transport model in a multiphase, variably saturated, porous soil medium. In this
      paper, a multicomponent PCB mass-transport model is presented that assumes
      evaporation is an important removal mechanism and that is based on first-order
      mass transfer between the interface of PCB films and the bulk steam. The model
      was calibrated using the experimental data, and the calibrated model was verified
      by computational mass-balance checks and comparisons with laboratory-scale column
      experimental results. From a qualitative point of view, the calibrated model
      successfully simulated the transport of PCBs in variably saturated soil media.
      The calculated increase/decrease factors of physicochemical properties of PCBs as
      a function of temperature in the soil, water, and free phases were consistent
      with the model hypothesis of an evaporation process. The effects of mass-transfer
      coefficients and initial PCB concentrations in the soils on PCB removal rates
      were investigated using the numerical code. It was determined that the PCB
      removal rates were sensitive to mass-transfer coefficients and initial PCB
      concentrations. Although the steam:soil mass ratios required to achieve a given
      percentage removal were lower for lower initial PCB soil concentrations, steam:
      soil mass ratios required to achieve a given unit mass removal were higherfor
      lower initial PCB soil concentrations.

PMID- 11993887
TI  - In situ remediation of groundwater contaminated by heavy- and transition-metal
      ions by selective ion-exchange methods.
AB  - Laboratory studies were conducted to investigate the feasibility of using ion
      exchange resins in permeable reactive barriers (PRBs) for the remediation of
      groundwater contaminated by heavy and transition metals. Ion-exchange resins
      represent an essentially neglected class of materials which may, in addition to
      iron, activated carbon, and zeolites, prove effective for use in PRBs. Four
      resins were considered: two commercially available resins, Duolite GT-73 (Rohm
      and Haas) and Amberlite IRC-748 (Rohm and Haas), and two solvent-impregnated
      resins (SIRs). The SIRs were prepared from Amberlite IRA-96 (Rohm and Haas) and
      two different thiophosphoric extractants. All four resins are able to reduce
      cadmium, lead, and copper concentrations from 1000 microg/L (typical for
      contaminated groundwaters) to below 5 microg/L. Significantly, all of the resins
      are effective for the capture of cadmium, copper, and lead, even in the presence
      of CaCl2 and clay. Because of their high hydraulic conductivity, the use of these
      resins in clusters of wells, as an alternative to continuous walls, is considered
      in the design of effective PRBs. Numerical solution of the groundwater flow
      equations shows that, depending on the well configuration, most (or all) of the
      contaminated groundwater can pass through the resins. These results demonstrate
      the possibility of using selective ion-exchange resins as an effective, active
      material in PRBs for in situ groundwater remediation.

PMID- 11993888
TI  - Ecologically benign polymers: the case of maleic polyelectrolytes.
AB  - The paper discusses a series of results that evidence the favorable effect of
      maleic polyelectrolytes in different fields in which a protective action of the
      environment is attained: (i) the exploitation of geothermal water, which is a
      cleaner source of energy; (ii) the improvement or preservation of the structure
      of agricultural soils; (iii) the substitution of phosphates in detergents; and
      (iv) the reduction of chromium load of effluents from tanning plants.

PMID- 11993889
TI  - Selective separation of hydroxide from alkaline nuclear tank waste by liquid
      liquid extraction with weak hydroxy acids.
AB  - Recovery and recycle of caustic reagents in industrial processes offer potential
      means of pollution prevention, as investigated herein for particular needs
      related to the cleanup of alkaline nuclear waste. Specifically, the recovery of
      hydroxide from alkaline media by liquid-liquid extraction can be effected
      utilizing weak hydroxy acids, as demonstrated for NaOH utilizing a series of
      lipophilic fluorinated alcohols and alkylated phenols dissolved in 1-octanol.
      Extraction efficiency follows the expected order of acidity of the hydroxy acids,
      the phenols being the most efficient extractants among the compounds tested.
      After extraction, NaOH is effectively recoverable from the organic phase upon
      contact with water. The weakest hydroxy acids are the most efficiently stripped,
      NaOH recovery being nearly quantitative in a single contact. In competitive
      extraction experiments, good selectivity for hydroxide recovery over other anions
      such as nitrate and chloride was demonstrated. Since the order of extraction
      favors larger anions, the exceptional preference for hydroxide implies that the
      extraction occurs by deprotonation of the hydroxy acids in a cation-exchange
      process. Stripping therefore occurs by hydrolysis to regenerate the neutral
      hydroxy acid, liberating NaOH to the aqueous phase. Since hydroxide equivalents
      rather than actual hydroxide ions are transferred to the solvent, the process is
      termed "pseudohydroxide extraction." Hydroxide recovery from a simulant of
      alkaline nuclear tank waste (Hanford DSSF simulant) was also demonstrated in
      repeated extraction and stripping cycles.

PMID- 11993890
TI  - Reflections on the medical profession during an Alaskan cruise.

PMID- 11993891
TI  - Primary care doctors' practice in the management of adult asthma patients.
AB  - There is apparent disparity between the international guidelines on asthma
      management and the current practice in reality. This can be attributed to both
      patient's and doctor's factors. This study examines the practice of asthma
      management by a group of family physicians using a self-administered
      questionnaire. This comprises questions relating to the main principles of asthma
      management set by international guidelines. The results showed that majority of
      the doctors (>90%) in the study reviewed patient's asthma status based on
      symptoms, educate their patients on types of asthma medications and advised them
      on allergen avoidance including smoking. Fewer of them (50 to <90%) check trigger
      factors or inhaled device technique, nocturnal symptoms or ER visits. Even fewer
      doctors (<50%) bothered to check the patient's peak expiratory flow rate (PEFR)
      or used spirometry.

PMID- 11993892
TI  - Prevalence of hepatitis G virus infection in patients with liver diseases in
      Singapore.
AB  - The prevalence of hepatitis G virus (HGV) infection in patients with liver
      diseases in Singapore and its pathogenic role in these patients was studied. One
      hundred and forty-eight patients who had chronic hepatitis or acute non A-E
      hepatitis were studied. Presence of HGV RNA was determined by nested polymerase
      chain reaction of the 5'non-coding region of the virus in all the patients.
      Hepatitis G IgG antibody to the envelope (E2) antigen was tested with an enzyme
      immunoassay (Boehringer Mannheim, Singapore) in 76 of them. Most patients (93%)
      were ethnically Chinese, predominantly males (74%) and chronic hepatitis B (72%)
      patients. Others had chronic hepatitis C (19%) or cryptogenic cirrhosis (6%).
      Four patients had acute non A-E hepatitis. HGV RNA and anti-HGenv were present in
      3.5% and 8.3% of those with chronic liver disease. HGV infection did not account
      for any of the acute non A-E hepatitis and most of the cryptogenic cirrhosis.

PMID- 11993893
TI  - Birth prevalence of Down syndrome in Singapore from 1993 to 1998.
AB  - OBJECTIVE: To examine the livebirth prevalence rate of Down Syndrome in Singapore
      from 1993 to 1998. DESIGN: Index cases for the National Birth Defects Register
      were obtained from all neonatal nurseries in Singapore, all hospital discharge
      summaries, cytogenetic and pathology reports from all pathology laboratories in
      Singapore and from the compulsory reporting of all termination of pregnancy cases
      and stillbirths delivered. SETTING: Information for the Register was obtained
      from case notes retrieved from the medical record offices, antenatal clinics,
      cytogenetic laboratories, pathology departments and the Registry of Births and
      Deaths. SUBJECTS: All foetuses with Trisomy 21 diagnosed prenatally together with
      livebirths and stillbirths with Down Syndrome diagnosed at or after birth were
      identified from the Registry database. MAIN OUTCOME MEASURES: Prevalence of Down
      Syndrome RESULTS: From 1993 to 1998, there were 295 Down Syndrome livebirths,
      four stillbirths and 197 Down Syndrome foetuses aborted. There has been an
      increasing number of Down Syndrome foetuses diagnosed antenatally ending in
      termination and this is accompanied by a falling trend in the Down Syndrome
      livebirth rate in the same years from 1.17 to 0.89 per 1000 total live births.
      This is despite an expected increase in Down Syndrome livebirth rate obtained by
      modelling maternal Down Syndrome age-related risks on the maternal age
      distribution over the years. CONCLUSIONS: The livebirth prevalence of Down
      Syndrome in Singapore has fallen over the years from 1.17/1000 livebirths in 1993
      to 0.89/1000 livebirths in 1998 due to antenatal diagnosis and selective
      termination.

PMID- 11993894
TI  - Evaluation of the hypoglycemic and anti-oxidant activities of Morinda officinalis
      in streptozotocin-induced diabetic rats.
AB  - AIM OF STUDY: The aim was to investigate the hypoglycemic and anti-oxidant
      activities of the dried roots of Morinda officinalis in streptozotocin-induced
      diabetic rats. METHODOLOGY: An ethanolic extract of the dried roots of Morinda
      officinalis and its three fractions (ethyl acetate, n-butanol and water) were
      obtained. We evaluated the hypoglycemic effects of three different single doses
      of the crude extract and its fractions in normal and diabetic rats for three
      hours after administration. Administration of the extract at 150 mg/kg twice
      daily for 10 days to the diabetic rats was also carried out. The effects of the
      10-day treatment on the fasting serum glucose, insulin, total cholesterol,
      triglycerides, body weight, food intake, fluid intake, hepatic superoxide
      dismutase (SOD), catalase (CAT) activities, reduced glutathione (GSH),
      thiobarbituric acid reactive substances (TBARS) and renal TBARS levels were
      monitored. RESULTS: In the three-hour dose response study, the crude ethanolic
      extract reduced the fasting serum glucose levels of the diabetic rats
      significantly at 150 mg/kg but increased those of the normal rats significantly
      at 600 mg/kg only. The water fraction demonstrated a dose dependent hypoglycemic
      effect in the diabetic rats whereas the n-butanol fraction increased the fasting
      serum glucose levels of the diabetic rats significantly at 50 mg/kg only within
      three hours after administration. The 10-day oral administration of the extract
      reduced the fasting serum glucose, hepatic and renal TBARS level and
      significantly increased the hepatic SOD and CAT activities as well as GSH levels.
      CONCLUSION: The results indicate that the dried roots of Morinda officinalis
      possess hypoglycemic, hyperglycemic and anti-oxidant properties.

PMID- 11993895
TI  - In vitro adsorption of lithium by bentonite.
AB  - BACKGROUND: Lithium poisoning is currently managed using a combination of
      supportive care and urgent haemodialysis in severe cases. Activated charcoal as a
      gut decontaminant has been found to be ineffective. The use of Sodium Polystyrene
      Sulphonate (SPS) as an adsorbent has been found to be effective in some studies.
      However, there have been case reports of gut necrosis and perforation occurring
      when SPS was used for the treatment of hyperkalaemia in post operative patients
      or patients with renal failure. Bentonite is a known adsorbent that has been used
      in the management of paraquat poisonings. The purpose of this study was to
      determine the ability of bentonite to adsorb lithium. METHOD: 4.5 g of lithium
      carbonate was dissolved in 1.5 L of deionised water to form the stock solution.
      50 mL aliquots of this stock solution were added to 50 mL of either distilled
      deionised water (pH 7) or simulated gastric fluid (pH 1.2). Bentonite of either
      0.75, 1.5 or 4.5 g was then added to simulate 5:1, 10:1 and 30:1 ratio of
      adsorbent-to-drug. Controls were made with no bentonite added. The resulting
      mixture was placed on a shaker for five minutes before being filtered. The
      filtrate was diluted and batch analysed for lithium using atomic absorption
      spectrophotometry. RESULTS: Bentonite decreased the concentration of lithium
      recovered from the filtrate by 20.55% in deionised water compared to 48.09% in
      simulated gastric fluid at a bentonite:lithium ratio of 30:1 (p value 0.005).
      CONCLUSION: This study shows that bentonite is an effective adsorbent for
      lithium. The effect is enhanced in simulated gastric fluid. In vivo studies are
      being planned for clinical correlation.

PMID- 11993896
TI  - A study of the concordance between endoscopic gastritis and histological
      gastritis in an area with a low background prevalence of Helicobacter pylori
      infection.
AB  - The concordance between endoscopic and histological gastritis was determined in
      52 patients referred for upper gastrointestinal endoscopy. The study was
      conducted in Northeastern Peninsular Malaysia, an area with a low background
      prevalence of H. pylori infection. Endoscopic and histological gastritis were
      assessed in accordance with the Sydney System. The results showed poor
      concordance between endoscopic and histological gastritis even after
      reclassifying mild endoscopic gastritis as normal. The low prevalence of H.
      pylori was validated in this study.

PMID- 11993897
TI  - Persistent ectopic pregnancy--a case report.
AB  - The following case report describes a case of persistent ectopic pregnancy
      following laparoscopic segmental salpingectomy. The patient had an unusual
      presentation of acute abdomen and focal haemorrhage from omental implantation of
      the trophoblastic tissue.

PMID- 11993898
TI  - Laparoscopic management of an ovarian pregnancy.
AB  - Ovarian pregnancy is a rare form of ectopic pregnancy. Here we report one such
      case that was successfully treated laparoscopically.

PMID- 11993899
TI  - Antero-medial orbital masses associated with nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) involves the orbits through direct
      extension to the orbital apex via the cavernous sinus. Anterior orbital masses
      are very rare with only a few anecdotes in the literature about an anterior
      spread via nasal cavity or tumour arising de novo from the lacrimal sac. Reactive
      lymphoid hyperplasia in the orbit has never been reported in association with
      NPC. MATERIALS AND METHODS: Three cases that presented with antero-medial orbital
      mass in association with NPC are described. Two of the three cases including one
      with bilateral orbital mass, had biopsy proven NPC in the orbit and presented
      with tearing due to lacrimal sac involvement with a palpable mass in the
      anteromedial orbit. The third case presented with a left antero-medial orbital
      mass, which on biopsy proved to be a reactive lymphoid hyperplasia. He was
      detected to have NPC while investigating the orbital mass. All had raised serum
      levels of IgA against Epstein-Barr virus (EBV). DISCUSSION: The possible mode of
      spread in our case with bilateral involvement is most likely to be a metastasis,
      though a microscopic anterior spread through the nasal cavity and nasolacrimal
      duct could not be ruled out despite there being no evidence of tumour in the
      original site or nasal cavity. In the second case, the tumour spread from the
      nasal cavity into the orbit is clearly via the nasolacrimal duct. The third
      patient presents an interesting association of lymphoproliferative disorder and
      NPC with Epstein-Barr virus infection. CONCLUSION: Anterior orbital masses
      involving nasolacrimal duct and lacrimal sac are rare in NPC, but can occur. A
      rare association of a reactive lymphoid hyperplasia in the orbit with NPC is
      described.

PMID- 11993900
TI  - Assessing the risk of vertebral osteoporosis.
AB  - Assessment of osteoporosis includes an accurate diagnosis, a consideration of the
      differential diagnosis, and prognostic assessment. Diagnosis of osteoporosis is
      based on bone mineral density (BMD) measurements and is defined as a BMD value
      that is 2.5 standard deviations or more below the average value in young healthy
      women (T score < or = -2.5 SD). Established osteoporosis is defined as a T-score
      of < or = -2.5 SD in the presence of a prior fragility fracture. The assessment
      of prognosis is important for defining intervention thresholds. Future fracture
      risk depends not only on BMD, but also on age. In addition, a variety of risk
      factors have been identified that increase fracture risk over and above that
      provided by BMD and age. Of particular importance is a prior fragility fracture,
      low body mass index and use of corticosteroids. The combination of independent
      risk factors permits a more accurate stratification of risk so that more patients
      at high risk can be identified. Risk of future fracture is optimally expressed as
      a probability. Ten-year fracture probabilities are appropriate for clinical use.
      The impact of BMD, age and other risks on fracture probability have recently been
      determined and provide a mechanism for optimising assessment of patients so that
      treatments can be efficiently directed to those most in need.

PMID- 11993901
TI  - Clinics in diagnostic imaging (70). Bilateral sacroiliitis due to ankylosing
      spondylitis.
AB  - A 15-year-old boy was incidentally found to have bilateral sacroiliitis.
      Radiographs showed erosions and subchondral sclerosis of both sacroiliac joints.
      His ESR was raised and HLA-B27 was positive. Presumptive diagnosis was ankylosing
      spondylitis. The clinical and imaging features, including the radiographical
      classification, of sacroiliitis are discussed. Knowledge of the patterns of
      distribution and correlation with clinical manifestations aid in differentiating
      among the various causes of sacroiliitis.

PMID- 11993902
TI  - Effect of a trapping force on a photon-counting histogram.
AB  - A theoretical study of the effect of a harmonic trapping force on the
      distribution of the fluorescence photon counts from Brownian particles is
      reported. The research of by Chen et al. [Biophys. J. 77, 553 (1999)] is
      extended. Simulations of the photon-counting histograms indicate that the
      trapping force parameters can be estimated from changes in the shapes of the
      histograms, at least for microspheres.

PMID- 11993903
TI  - Selective optical detection of aromatic vapors.
AB  - A sensitive layer system of amorphous Teflon AF on silver has been coated on a
      glass substrate. With a monochromatic light source the reflectivity of the layer
      system as a function of the angle of incidence exhibits the surface-plasmon
      resonance as well as a set of leaky-mode resonances. These optical resonance
      phenomena are sensitive to small refractive-index changes that may be induced by
      diffusion of particles into the Teflon AF layer. On the basis of this effect, the
      aromatic vapors benzene; toluene; and o-, p-, and m-xylene have been investigated
      with different vapor concentrations. By selection of a distinct angle at a
      particular resonance, dynamic measurements can be performed. Assuming a diffusion
      process in accordance with Fick's law, the diffusion profile can be calculated as
      a function of time. As described by the Lorentz-Lorenz relation a refractive
      index profile is induced that consequently interacts with the electromagnetic
      fields of the optical modes. With the function of the diffusion-induced
      refractive-index profile the shift of the resonance lines can be calculated from
      the measured reflectivity change as a function of time. The characteristic
      diffusion coefficients of the particular vapor allow for a distinction between
      the different types of aromate, even between the different xylenes.

PMID- 11993904
TI  - Light scattering by dust particles in microgravity: polarization and brightness
      imaging with the new version of the PROGRA2 instrument.
AB  - A new version of the PROGRA2 instrument, dedicated to measuring the polarization
      phase function of various kinds of solid particles, allows obtaining maps of
      polarization and brightness with a spatial resolution of a few tens of
      micrometers. The measurements are conducted in microgravity during parabolic
      flights to ensure random distribution and orientation of the particles. The
      results of the first two sessions are presented. Comparison between measurements
      and Mie theory modeling for glass spheres shows that the instrument works well
      and that accurate results can be obtained even at small phase angles. Results for
      irregularly shaped particles are also presented.

PMID- 11993905
TI  - Design of optimal polarimeters: maximization of signal-to-noise ratio and
      minimization of systematic error.
AB  - The relationship between system condition and signal-to-noise ratio (SNR) in
      reconstructed Stokes parameter images is investigated for rotating compensator,
      variable retardance, and rotating analyzer Stokes vector (SV) polarimeters. A
      variety of optimal configurations are presented for each class of systems. The
      operation of polarimeters is discussed in terms of a four-dimensional conical
      vector space; and the concept of nonorthogonal bases, frames, and tight frames is
      introduced to describe the operation of SV polarimeters. Although SNR is an
      important consideration, performance of a polarimeter in the presence of errors
      in the calibration and alignment of the optical components is also important. The
      relationship between system condition and error performance is investigated, and
      it is shown that an optimum system from the point of view of SNR is not always an
      optimum system with respect to error performance. A detailed theory of error
      performance is presented, and the error of a SV polarimeter is shown to be
      related to the stability and condition number of the polarization processing
      matrices. The rms error is found to fall off as the inverse of the number of
      measurements taken. Finally, the concepts used to optimize SV polarimeters are
      extended to be useful for full Mueller matrix polarimeters.

PMID- 11993906
TI  - Characteristics of short-period blazed fiber Bragg gratings for use as macro
      bending sensors.
AB  - The characteristics of short-period blazed fiber Bragg gratings for use as macro
      bending sensors are discussed. This sensor is able to detect macro bending with
      the transmitted power variation of the first side mode in the blazed fiber Bragg
      grating. Since an incident ray experiences different variations of tilt angles
      with respect to bending direction, the blazed fiber Bragg grating has different
      coupling efficiencies of the first side mode, which can be reduced considerably
      in the case of twisted blazed fiber Bragg gratings.

PMID- 11993907
TI  - Alignment tolerances for plane-wave to single-mode fiber coupling and their
      mitigation by use of pigtailed collimators.
AB  - We discuss the efficiency with which coherent plane waves can be coupled to
      single-mode fibers in the presence of deterministic or stochastic misalignments
      of the fiber relative to the focal point of a lens. We point out how the
      alignment demands can be relaxed by means of graded-index-lens fiber-pigtailed
      collimators.

PMID- 11993908
TI  - Seventeenth-century telescope optics of Torricelli, Divini, and Campani.
AB  - Optics of telescope makers Torricelli, Divini, and Campani dating back to the
      17th century have been tested interferometrically. It was found that the optical
      polishing technology had progressed to thorough control over the surface figure
      and finish, while the nearly paraxial conditions of the aperture remained
      constant. The instruments that were examined exemplify the knowledge of optics of
      that time, particularly with respect to the early use of erector units in
      terrestrial telescopes.

PMID- 11993909
TI  - Digital-holographic interferometry with an image-intensifier system.
AB  - A method for recording digital holograms on an image intensifier coupled with a
      CCD sensor is presented. The advantage of the image intensifier is that it can be
      gated (electronic shutter action produced by controlling of the image
      intensifier's photocathode voltage). This allows us to record holograms with a
      short exposure time. Two holograms of an object submitted to dynamical
      displacements (e.g., vibrations) are recorded by two short exposures. The phase
      of the wave front recorded at different times is calculated from the recorded
      intensity by use of a digital Fourier-transform method. By comparison of the
      phases recorded it is possible to get the displacement of the object during a
      short interval. Experimental results are presented, and the problems related to
      the noise and to the spatial resolution are discussed.

PMID- 11993910
TI  - Measurement of temperature profile of a gaseous flame with a Lau phase
      interferometer that has circular gratings.
AB  - We have investigated the utility of a Lau phase interferometer with circular
      gratings and a white-light source to measure the temperature and temperature
      profile of an axisymmetric flame. The temperature measured with a Lau phase
      interferometer is in good agreement with the temperature measured with a
      thermocouple and multilogger. Detailed theoretical analysis and experimental
      investigation are presented.

PMID- 11993911
TI  - Glass-fiber self-mixing intra-arterial laser Doppler velocimetry: signal
      stability and feedback analysis.
AB  - We have developed a blood velocimeter based on the principle of self-mixing in a
      semiconductor laser diode through an optical fiber. The intensity of the light is
      modulated by feedback from moving scattering particles that contain the Doppler
      shift frequency. Upon feedback the characteristics of the laser diode change. The
      threshold current decreases, and an instable region may become present above the
      new threshold. The amplitude of the Doppler signal turns out to be related to the
      difference in intensity between situations with and without feedback. This
      amplitude is highest just above feedback. The suppression of reflection from the
      glass-fiber facets is of paramount importance in the obtaining of a higher signal
      to-noise ratio. Using an optical stabilization of the feedback, we optimized the
      performance of the laser-fiber system and the Doppler modulation depth and
      clarified its behavior with a suitable physical model. We also investigated the
      effect of the finite coherence length of the laser. We tested the efficiency of
      the self-mixing velocimeter in vivo with the optical glass fiber inserted in the
      artery with endoscopic catheters, both in upstream and in downstream blood flow
      conditions. For the latter we used a special side-reflecting device solution for
      the fiber facet to allow downstream measurements.

PMID- 11993912
TI  - Phase-shifting birefringent scatterplate interferometer.
AB  - We realized what we believe is a new phase-shifting scatterplate interferometer
      by exploiting the polarization characteristics of a birefringent scatterplate.
      The common-path design of the interferometer reduces its sensitivity to
      environmental effects, and phase shifting allows quick and accurate quantitative
      measurements of the test surface. A major feature of the birefringent
      scatterplate approach for phase shifting is that no high-quality optical
      components are required in the test setup. The theory of the interferometer is
      presented, the procedure for the fabrication of the birefringent scatterplate is
      described, and experimental results are shown.

PMID- 11993913
TI  - Refractive-index changes caused by proton radiation in silicate optical glasses.
AB  - We have studied experimentally, by using a differential interferometric
      technique, the effect of proton radiation on the refractive index of commercial
      (Schott) silicate crown glasses, BK7 and LaK9, and their radiation-resistant
      counterparts. The strongest effect was observed for the radiation-hard lanthanum
      crown LaK9G15: At a 0.65-Mrad dose the index change was approximately 3 x 10(-5).
      Radiation-hard glasses are used in optical systems operating in radiation
      environments because they prevent spectral transmission degradation in the
      visible. However, such glasses are not protected against radiation-induced
      refractive-index perturbations, and a diffraction-limited optical system based on
      such glasses may fail owing to radiation-induced aberrations.

PMID- 11993914
TI  - Influence of refractive-index mismatch in high-resolution three-dimensional
      confocal microscopy.
AB  - The effects of the refractive-index mismatch in confocal laser scanning
      microscopy were extensively studied. The axial aberration induced in the case of
      fluorescent microspheres was measured. The data were used to take into account
      the mismatch-induced aberrations and to consider object-size influence. Then we
      focused on the effect of refractive-index mismatch on the effective system's
      point-spread function under different mismatch conditions and on depth of
      focusing. We experimentally verified that the peak of the point-spread function
      intensity profile decreases and the point-spread function itself progressively
      broadens as a function of the combined effect of the refractive-index mismatch
      and of the penetration depth, leading to a worsening of the system's overall
      performances. We also performed these same measurements by embedding
      subresolution beads in an oocyte's cytoplasm, which can be considered a turbid
      medium. We found evidence consistent with the previously developed theoretical
      model; in particular we found a strong dependence of the intensity peak on the
      focusing depth.

PMID- 11993915
TI  - Analysis of Monte Carlo methods applied to blackbody and lower emissivity
      cavities.
AB  - Monte Carlo methods are often applied to the calculation of the apparent
      emissivities of blackbody cavities. However, for cavities with complex as well as
      some commonly encountered geometries, the emission Monte Carlo method experiences
      problems of convergence. The emission and absorption Monte Carlo methods are
      compared on the basis of ease of implementation and convergence speed when
      applied to blackbody sources. A new method to determine solution convergence
      compatible with both methods is developed, and the convergence speeds of the two
      methods are compared through the application of both methods to a right-circular
      cylinder cavity. It is shown that the absorption method converges faster and is
      easier to implement than the emission method when applied to most blackbody and
      lower emissivity cavities.

PMID- 11993916
TI  - Thermally assisted recording of holographic gratings in semicrystalline
      azobenzene-containing polymers.
AB  - We examine optically induced birefringence in semicrystalline azopolymer films
      that are held at glass-transition temperature Tg. The birefringence increases
      markedly after interception of the pump beam; the saturation value depends on
      exposure time. In addition, the induced birefringence is completely erased by
      irradiation with a circularly polarized beam at Tg. Using this thermally assisted
      method, we demonstrate the holographic recording of a test image. The intensity
      of the diffracted beam also increases after interception of the writing beams.
      Furthermore, the retrieved image is found to have a resolution of approximately
      30 lp/mm. This resolution is comparable with that of the optical setup that is
      used. Accordingly, the thermally assisted recording by use of semicrystalline
      azopolymers is a promising method for reversible holographic storage.

PMID- 11993917
TI  - Variable-addressability electronic binocular system.
AB  - The eye's acuity varies across its field of view (FOV), decreasing to 10% of its
      axial value at only 20 degrees. We describe an optical system that radially
      remaps the pixels of a miniature display or sensor to match the varying acuity of
      the eye across its FOV. The variable-acuity technique increases the FOV of an
      electronic binocular system without any apparent loss in image quality. The
      result is a better, more efficient human-machine interface.

PMID- 11993918
TI  - Iridescent colors on seashells: an optical and structural investigation of
      Helcion pruinosus.
AB  - Many animal species display exceptionally bright iridescent coloration caused by
      interference or diffraction from a periodic surface microstructure. Although many
      mollusks are colored, only few utilize such a form of structural coloration. We
      are not referring to the well-known pearly appearance that is due to the nacreous
      layer found on the inner surfaces of most shells, but to small brightly colored
      spots on the outer surface. The Helcion pruinosus is one such example. We show by
      optical measurements and scanning electron microscopy (SEM) that coloration in
      this shell is indeed of a structural nature based on thin-film interference from
      a layered quarter-wave stack tilted by approximately 24 degrees with respect to
      the outer surface. The microstructure is embedded in the transparent top layer of
      the shell approximately 50 microm below the surface. By comparing the SEM and
      optical measurements, we were able to establish that the layered structure is
      made from a birefringent material (crystalline aragonite) giving slightly
      different spectral peaks for S- and P-type reflections.

PMID- 11993919
TI  - Effects of polydispersity of chainlike aggregates on light-scattering properties
      and data inversion.
AB  - A systematic evaluation of the effects of polydispersity of chainlike aggregates
      in terms of primary particle number density and size on the scattering quantities
      and data inversion is presented. For aggregates with refractive index in the
      range absolute value(m-1) = 0.8-1.2, average size parameter x < 0.40, and primary
      particle number Np < 20, it is shown that the effects of polydispersity of
      primary particle size on the light-scattering quantities are much stronger than
      the polydispersity of the number of primary particles per aggregate. For
      aggregates with polydisperse primary particle size, the assumption of
      monodispersity tends to underestimate the real and imaginary parts of the
      refractive index and the number of primary particles. Specifically, for values of
      the distribution width sigma greater than 0.10, the effect of polydispersity of
      the size of primary particles must be considered in the data inversion schemes.
      Furthermore, in the same range of values for the refractive index, particle size
      parameter, and primary particle number, the assumption of monodispersity for
      aggregates with polydisperse particle number tends to underestimate the value of
      the real part of the refractive index and overestimate the value of the imaginary
      part of the refractive index and primary particle size. However, for values of
      the distribution width sigma less than 0.60, the effects of polydispersity of
      primary particle number can be neglected. In addition, the suitable pairing sets
      of the measured scattering quantities for data inversion are presented and
      discussed.

PMID- 11993920
TI  - Birefringent imaging spectrometer.
AB  - A Fourier-transform imaging spectrometer, believed to be novel, based on the
      Savart polariscope is presented. There is no slit in this instrument, which means
      that it has a high throughput. The principle and the system configuration are
      described. Several preliminary experimental results are shown.

PMID- 11993921
TI  - Evaluation of crystallinity in TiO2 films with mixed structures grown on MgO
      (001) substrates by argon-ion beam sputtering based on infrared reflection
      absorption spectra.
AB  - TiO2 films with thicknesses (d) above 15 nm were grown on optically polished
      surfaces of MgO (001) substrates held at 400 degrees C by sputtering a Ti target
      with an argon-ion beam when the partial pressure of O2 was kept at 1.1 x 10(-2)
      Pa. X-ray diffraction patterns show that TiO2 films with d < 56 nm are composed
      of an a-axis anatase-type structure, whereas those with d > 56 nm are composed of
      a mixture of phases with the c-axis parallel to the film surface. The thickness
      dependence of the infrared reflection-absorption spectra shows that TiO2 films
      with d < 56 nm are composed of both anatase and amorphous phases, whereas those
      with d > 56 nm are composed of anatase, rutile, and amorphous phases. The
      crystallinity in TiO2 films is also evaluated from the infrared reflection
      absorption spectra by comparison of the observed and the calculated results
      determined from the dielectric function of anisotropic TiO2 bulk single crystal.

PMID- 11993922
TI  - Omnidirectional reflection from finite periodic and Fibonacci quasi-periodic
      multilayers of alternating isotropic and birefringent thin films.
AB  - Omnidirectional reflection from periodic and Fibonacci quasi-periodic multilayers
      that are embedded in an isotropic medium is further analyzed. Besides the
      isotropic structures, birefringent structures are considered that comprise
      uniaxial layers in the principal-axis system, alternating with isotropic layers
      so that the refractive index of isotropic layers is equal to the principal
      extraordinary refractive index of the uniaxial layers. The transfer-matrix method
      is applied, and the same formalism is used forboth the isotropic and the uniaxial
      media in the principal-axis system. Simple and original relations are obtained
      for the invariant of the one-dimensional Fibonacci sequences at oblique
      incidence. Numerical examples are given comparatively for the isotropic and the
      birefringent structures in the case of periodic and Fibonacci quasi-periodic
      sequences at different values of the refractive indices.

PMID- 11993923
TI  - Properties of titanium dioxide films prepared by reactive electron-beam
      evaporation from various starting materials.
AB  - There is a wide choice of starting materials for the production of titanium
      dioxide films by reactive electron-beam evaporation. We have investigated the
      specific merits of these materials in terms of refractive index, stress, and
      abrasion resistance of the resultant titanium dioxide films. The suboxides TiO,
      Ti2O3, and Ti3O5 as well as titanium dioxide and titanium metal were reactively
      evaporated, and titanium dioxide films free of absorption were obtained on
      substrates at 25 and 250 degrees C. On unheated substrates the refractive index,
      which varies from 2.06 to 2.22, the stress, and the abrasion resistance all
      depend on the starting material used. On substrates heated to 250 degrees C the
      refractive indices of all films lie closely about 2.4, and all films show high
      tensile stress and good abrasion resistance.

PMID- 11993924
TI  - Efficiency and polarization performance of a multilayer-coated laminar grating in
      the 6.5-6.9-nm wavelength region.
AB  - We applied a Mo/B4C multilayer coating to a laminar holographic grating with 2400
      grooves/mm and a 1-m radius of curvature. By use of synchrotron soft x rays the
      multilayer-coated grating was evaluated to have diffraction efficiencies of 3.1%
      and 0.017% for s- and p-polarized radiation, respectively, at a 6.7-nm wavelength
      at a 45.35 degrees grazing angle of incidence in the +1 (inside) grating order.
      Thus the polarizance was estimated to be 98.9% at least. The zero-order peak was
      suppressed by the destructive interference caused by the groove profile.

PMID- 11993925
TI  - Quantitative dental measurements by use of simultaneous frequency-domain laser
      infrared photothermal radiometry and luminescence.
AB  - Modulated (frequency-domain) infrared photothermal radiometry (PTR) is used as a
      dynamic quantitative dental inspection tool complementary to modulated
      luminescence (LM) to quantify sound enamel or dentin. A dynamic high-spatial
      resolution experimental imaging setup, which can provide simultaneous
      measurements of laser-induced modulated PTR and LM signals from defects in teeth,
      has been developed. Following optical absorption of laser photons, the
      experimental setup can monitor simultaneously and independently the nonradiative
      (optical-to-thermal) energy conversion by infrared PTR and the radiative
      deexcitation by LM emission. The relaxation lifetimes (tau1, tau2) and optical
      absorption, scattering, and spectrally averaged infrared emission coefficients
      (mu(alpha), mu(s), mu(IR)) of enamel are then determined with realistic three
      dimensional LM and photothermal models for turbid media followed by
      multiparameter fits to the data. A quantitative band of values for healthy enamel
      with respect to these parameters can be generated so as to provide an explicit
      criterion for the assessment of healthy enamel and, in a future extension, to
      facilitate the diagnosis of the onset of demineralization in carious enamel.

PMID- 11993926
TI  - Improvement of image quality in diffuse optical tomography by use of full time
      resolved data.
AB  - In the field of diffuse optical tomography (DOT), it is widely accepted that time
      resolved (TR) measurement can provide the richest information on photon migration
      in a turbid medium, such as biological tissue. However, the currently available
      image reconstruction algorithms for TR DOT are based mostly on the cw component
      or some featured data types of original temporal profiles, which are related to
      the solution of a time-independent diffusion equation. Although this methodology
      can greatly simplify the reconstruction process, it suffers from low spatial
      resolution and poor quantitativeness owing to the limitation of effectively
      applicable data types. To improve image quality, it has been argued that
      exploiting the full TR data is essential. We propose implementation of a DOT
      algorithm by using full TR data and furthermore a variant algorithm with time
      slices of TR data to alleviate the computational complexity and enhance noise
      robustness. Compared with those algorithms where the featured data types are
      used, our evaluations on the spatial resolution and quantitativeness show that a
      significant improvement in imaging quality can be achieved when full TR data are
      used, which convinces the DOT community of the potential advantage of the TR
      domain over cw and frequency domains.

PMID- 11993927
TI  - Monte Carlo model and single-scattering approximation of the propagation of
      polarized light in turbid media containing glucose.
AB  - We present a single-scattering model as well as a Monte Carlo model of the effect
      of glucose on polarized light in turbid media. Glucose alters the Mueller-matrix
      patterns of diffusely backscattered and forward-scattered light because glucose
      molecules rotate the polarization plane of linearly polarized light. For example,
      the angles of rotation in Mueller-matrix elements S21 and S12 are linearly
      related to the concentration of glucose and increase with the source-detector
      distance. In the nondiffusion regime, the two models agree well with each other.
      In the diffusion regime, the single-scattering model is invalid, but there still
      exists a linear relationship between the angles of rotation in the Mueller-matrix
      elements and the concentration of glucose, which is predicted by the Monte Carlo
      model.

PMID- 11993928
TI  - Study of filtered light on potential retinal photic hazards with operation
      microscopes used for ocular surgery.
AB  - There have been numerous reports of retinal photic injury from operation
      microscopes used during cataract surgery. The risk of injury has been associated
      with the intensity of the light directed into the eye, short-wavelength emission,
      user technique, exposure time, and direct axial lighting. We evaluated use of
      light transmission filters to modify a tungsten-halogen light source spectrum to
      reduce the risk of retinal photic injury. A two-light source filter combination
      was found with a color profile acceptable for intraocular surgery that reduces
      the risk of retinal photic injury by a factor of approximately 2.5.

PMID- 11993929
TI  - High-resolution full-field optical coherence tomography with a Linnik microscope.
AB  - We describe an original microscope for high-resolution optical coherence
      tomography applications. Our system is based on a Linnik interference microscope
      with high-numerical-aperture objectives. Lock-in detection of the interference
      signal is achieved in parallel on a CCD by use of a photoelastic birefringence
      modulator and full-field stroboscopic illumination with an infrared LED.
      Transverse cross-section (en-face, or XY) images can be obtained in real time
      with better than 1-microm axial (Z) resolution and 0.5-microm transverse (XY)
      resolution. A sensitivity of approximately 80 dB is reached at a 1-image/s
      acquisition rate, which allows tomography in scattering media such as biological
      tissues.

PMID- 11993930
TI  - Painting analysis of meiotic metaphase I configurations of the germ line-limited
      chromosomes in Acricotopus.
AB  - Meiotic metaphase I configurations and pairing behavior of the germ line-limited
      chromosomes (= Ks) in the chironomid Acricotopus lucidus were analyzed by
      chromosome painting using specific probes of the three soma chromosomes (= Ss)
      and of their individual arms. The Ks are derived from the Ss and possess large S
      homologous sections. Beside regular K and S bivalents, we also observed
      frequently K multivalents, e.g. trivalents, mainly quadrivalents, but also penta-
      and hexavalents, composed of the same K type in metaphases I. Chiasmata
      predominately occur within the S-homologous sections, probably ensuring a correct
      segregation and the transmission of a set of Ks to the next generation. Because K
      bivalents are almost exclusively autobivalents in A. lucidus formed by earlier
      sister chromatids, this multivalent formation with crossover also between
      homologous but non-identical Ks leads to genetic recombination within a K type.
      Rarely, quadrivalents composed of non-homologous Ks but derived from the same S
      were found. Therefore, these multivalents most probably resulted from crossover
      between homologous sections of morphologically different K types. This may result
      in new K types and might be important for the evolution of K type diversity in A.
      lucidus. In some cases, pairing-like associations between SIII and K4, which is
      derived from SIII, were observed in metaphases, indicating the possibility of
      crossover events and recombination between these chromosomes and so between the
      somatic and the germ-line restricted chromosome complements. Possible functions
      of additional copies of S sequences carried in the germ line are discussed.

PMID- 11993931
TI  - Complex structure of B-chromosomes in two mammalian species: Apodemus peninsulae
      (Rodentia) and Nyctereutes procyonoides (Carnivora).
AB  - B-chromosomes (Bs) of two mammalian species, raccoon dog
      (Nyctereutesprocyonoides, Carnivora) and Asian wood mouse (Apodemus peninsulae,
      Rodentia) were investigated using chromosome segment microdissection and double
      colour FISH. In the raccoon dog, all B-chromosomes showed homology with each
      other but not with the A-chromosomes. Two segment-specific probes (from proximal
      and distal parts of B) have been localized in corresponding chromosome parts,
      with significant variation in their sizes. In Asian wood mice, two types of B
      specific chromatin were revealed--B1 and B2. Most Bs were either B1 or B2
      specific; furthermore, some Bs were found to be composed of both types of
      chromatin. B-chromosome-specific libraries of A. peninsulae contain sequences
      homologous to the heterochromatic regions of sex and some A-chromosomes and
      dispersed repeated sequences. B1-specific probes gave signals on sex chromosomes
      of Apodemus speciosus and Apodemus agrarius. The origin and evolution of B
      chromosomes in mammals are discussed.

PMID- 11993932
TI  - Comparative analysis of the MSAT-160 repeats in four species of common vole
      (Microtus, Arvicolidae).
AB  - The highly repeated tandemly arranged satellite DNA from the MSAT-160 family has
      been studied in 4 species of common vole (the Microtus arvalis group). All the
      monomer units analysed were classified into 4 subfamilies on the basis of similar
      nucleotide substitutions. The first 3 subfamilies do not show any species
      specificity since they combine monomers from several of the vole species
      examined; the fourth subfamily contains monomer units with substitutions specific
      to M. arvalis. Certain monomers of different species within the first 3
      subfamilies display additional identical substitutions, making them more similar.
      Despite considerable similarity in monomer sequence within the subfamilies,
      specific features were found for each of the 4 species. A specific ratio of each
      type of monomer belonging to the corresponding subfamilies is typical of each
      species. In addition, the genomes of common vole species differ in the abundance
      of the MSAT-160 DNA, its pericentromeric location and organization. The
      mechanisms possibly involved in the evolution of the common vole MSAT-160
      sequences are discussed.

PMID- 11993933
TI  - Ancient tetraploidy and slow molecular evolution in Scaphiophryne: ecological
      correlates of speciation mode in Malagasy relict amphibians.
AB  - Karyotypes of three microhylid frog species of the Malagasy relict genus
      Scaphiophryne were studied: Scaphiophryne gottlebei, S. madagascariensis and S.
      spinosa. The latter two showed a plesiomorphic ranoid karyotype of 2n = 26. In
      contrast, tetraploidy was demonstrated in S. gottlebei, which constitutes an
      exceptional state among Malagasy amphibians. A combination of different banding
      techniques and of rDNA-FISH provided evidence for allopolyploidy in the species
      and for a completed subsequent functional and structural diploidization.
      Phylogenetic analysis of mitochondrial 16S rDNA sequences revealed a significant
      deceleration of nucleotide substitution rates in Scaphiophryne. The tetraploidy
      of S. gottlebei probably occurred early in their radiation. Ecological and
      behavioural patterns of Scaphiophryne probably favoured intraspecific gene flow
      and hybridization events, thereby leading to slow molecular substitution rates
      and to allopolyploid chromosome speciation in S. gottlebei.

PMID- 11993934
TI  - FISHing in the microwave: the easy way to preserve proteins. I. Colocalization of
      DNA probes and surface antigens in human leukocytes.
AB  - Most of the techniques for simultaneous visualization of proteic cell components
      and DNA probes are difficult to carry out. We have developed an alternative
      protocol for simultaneous visualization of DNA probes and cell surface antigens
      in human cells. The method exploits microwave energy to denature DNA and to
      anneal the probe after antigen fluorescent detection of unfixed cells previously
      embedded in a microgel. CD3 antigens and whole genome DNA probes or specific
      repetitive DNA sequences were colocalized in peripheral blood samples. The
      results show a strong, specific and consistent hybridization pattern in each cell
      that allowed correlation between cell subtype (PROTEINS) and nuclear phenotype
      (DNA).

PMID- 11993935
TI  - Chromosomal evolution of the Hapalemur griseus subspecies (Malagasy Prosimian),
      including a new chromosomal polymorphic cytotype.
AB  - A cytogenetic study has been performed on Hapalemur griseus caught in different
      locations of the eastern and northern forests of Madagascar. This allowed the
      determination of the more precise distribution areas of the different subspecies
      and the isolation of a new cytogenetic polymorphic subspecies of H. griseus. The
      chromosomal changes distinguishing the different subspecies are Robertsonian
      translocations and gain of heterochromatin. The phylogeny established on
      chromosome comparison is compatible with the geographic distribution of the
      subspecies.

PMID- 11993936
TI  - Aloe spp.--plants with vertebrate-like telomeric sequences.
AB  - Chromosome termini of most eukaryotes end in tracks of short tandemly repeated GC
      rich sequences, the composition of which varies among different groups of
      organisms. Plant species predominantly contain (TTTAGGG)n repeats at their
      telomeres. However, a few plant species, including members of Alliaceae and Aloe
      spp. (Asphodelaceae) were found to lack such Arabidopsis-type (T3AG3)n telomeric
      repeats. Recently, it has been proposed that the lack of T3AG3 telomeric repeat
      sequences extends to all species forming the Asparagales clade. Here, we analysed
      the composition of Aloe telomeres by single-primer PCR and fluorescence in-situ
      hybridization (FISH) with directly labelled Arabidopsis-type (TTTAGGG)28-43 DNA
      probe, and with vertebrate-type (TTAGGG)33-50 DNA and a (C3TA2)3 peptide nucleic
      acid (PNA) probe. It was found that Nicotiana tabacum contained Arabidopsis-type
      telomeric repeats, while Aloe telomeres lacked the corresponding FISH signals.
      Surprisingly, FISH with the highly specific vertebrate-type (C3TA2)3 PNA probe
      resulted in strong T2AG3-specific FISH signals at the ends of chromosomes of both
      Aloe and Nicotiana tabacum, suggesting the presence of T2AG3 telomeric repeats in
      these species. FISH with a long (TTAGGG)33-50 DNA probe also highlighted Aloe
      chromosome ends, while this probe failed to reveal FISH signals on tobacco
      chromosomes. These results indicate the presence of vertebrate-like telomeric
      sequences at the telomeres of Aloe spp. chromosomes. However, single-primer PCR
      with (TAG3)5 primers failed to amplify such sequences in Aloe, which could
      indicate a low copy number of T2AG3 repeats at the chromosome ends and/or their
      co-orientation and interspersion with other repeat types. Our results suggest
      that telomeres of plant species, which were thought to lack GC-rich repeats, may
      in fact contain variant repeat types.

PMID- 11993937
TI  - Topological organization of DNA molecules in the macronucleus of hypotrichous
      ciliated protozoa.
AB  - The DNA in the macronucleus of a hypotrichous ciliate occurs as millions of short
      molecules packed into dense chromatin bodies 0.1-2 microm in diameter. We have
      studied by electron microscopy the organization of DNA molecules in these
      chromatin bodies of macronuclei lysed in water at pH 9. Proteinase K treatment of
      lysed macronuclei progressively releases from chromatin bodies many rosettes of
      DNA molecules bound at one or both ends to a central core of protein. With longer
      treatment with proteinase K, rosettes disappear, leaving individual free DNA
      molecules. We propose that, in the native state, both ends of DNA molecules are
      bound through telomere-binding protein to a central core to form rosettes. Many
      rosettes, with collapsed DNA loops, aggregate to form a chromatin body. Chromatin
      bodies are believed to dissociate into individual collapsed rosettes to form the
      granules in the forward zone of the replication band. In the rear zone of the
      band, the rosettes dissociate, presumably as a result of release of telomere
      binding protein, which is preliminary to the replication of the DNA molecules.

PMID- 11993938
TI  - Isolation, characterization and chromosome localization of repetitive DNA
      sequences in bananas (Musa spp.).
AB  - Partial genomic DNA libraries were constructed in Musa acuminata and M.
      balbisiana and screened for clones carrying repeated sequences, and sequences
      carrying rDNA. Isolated clones were characterized in terms of copy number,
      genomic distribution in M. acuminata and M. balbisiana, and sequence similarity
      to known DNA sequences. Ribosomal RNA genes have been the most abundant sequences
      recovered. FISH with probes for DNA clones Radkal and Radka7, which carry
      different fragments of Musa 26S rDNA, and Radka14, for which no homology with
      known DNA sequences has been found, resulted in clear signals at secondary
      constrictions. Only one clone carrying 5S rDNA, named Radka2, has been recovered.
      All remaining DNA clones exhibited more or less pronounced clustering at
      centromeric regions. The study revealed small differences in genomic distribution
      of repetitive DNA sequences between M. acuminata and M. balbisiana, the only
      exception being the 5S rDNA where the two Musa clones under study differed in the
      number of sites. All repetitive sequences were more abundant in M. acuminata
      whose genome is about 12% larger than that of M. balbisiana. While, for some
      sequences, the differences in copy number between the species were relatively
      small, for some of them, e.g. Radka5, the difference was almost thirty-fold.
      These observations suggest that repetitive DNA sequences contribute to the
      difference in genome size between both species, albeit to different extents.
      Isolation and characterization of new repetitive DNA sequences improves the
      knowledge of long-range organization of chromosomes in

PMID- 11993939
TI  - Transport of 125I and 36Cl across an anion-exchange paper membrane.
AB  - The membrane characteristics controlling 125I and 36Cl transport across anion
      exchange paper membranes are examined using three different paper membranes
      treated with different anion exchange groups: a trimethylhydroxypropylamino
      group, a diethylaminoethyl group, and a 50% quaternary diethylaminoethyl group.
      The membrane permeability for 125I is higher than that for 36Cl in all cases.
      Treatment with trimethylhydroxypropylamino group improves the 125I diffusion
      process, and the use of 50% quaternary diethylaminoethyl group improves the 125I
      solution/membrane distribution process.

PMID- 11993940
TI  - Evaluation of potential chelating agents for radium.
AB  - The alpha-particle-emitting radionuclide 223Ra (t(1/2) = 11.4 d) is of interest
      for use in targeted radionuclide therapy. In order to provide radium-labeled
      monoclonal antibodies, the development of a chelator binding radium in a stable
      fashion is required. As a part of the search for potentially useful radium
      chelators, the relative stability of 223Ra-chelates with linear and cyclic
      chelating agents was evaluated by means of competition extraction experiments.

PMID- 11993941
TI  - PET quantitation and imaging of the non-pure positron-emitting iodine isotope
      124I.
AB  - A series of PET studies using phantoms is presented to characterize the imaging
      and quantitative performance of the positron-emitting iodine isotope 124I.
      Measurements were performed on the 2D-PET scanner GE 4096+ as well as on the
      Siemens PET scanner HRR+ operated in both 2D and 3D modes. No specific correction
      was applied for the gamma-rays emitted together with the positrons. As compared
      to 18F, in studies with 124I there is a small loss of image resolution and
      contrast, and an increase in background. The quantitative results varied between
      different scanners and various acquisition as well as reconstruction modes, with
      an average relative difference of -6 +/- 13% (mean+/-SD) in respect of the
      phantom radioactivity as measured with gamma-ray spectroscopy. We conclude that
      quantitation of a radiopharmaceutical labelled with 124I is feasible and may be
      improved by the development of specific corrections.

PMID- 11993942
TI  - A method for preparation and purification of 234Th.
AB  - An improved method to recover 234Th from depleted uranium has been developed. The
      method is based on solvent extraction and ion-exchange separations. The final
      thorium fraction has a high specific activity, about 1-3 PBq/mol Th, which makes
      it well suited for investigations, where a low thorium concentration is
      essential. The method is comparably fast, with a total processing time of 2 days.
      Another advantage is that the uranium fraction can be used as a 234Th generator
      for several years.

PMID- 11993943
TI  - Excitation functions of 85Rb(p,xn)(85m,g,83,82,81)Sr reactions up to 100 MeV:
      integral tests of cross section data, comparison of production routes of 83Sr and
      thick target yield of 82Sr.
AB  - The beta+ emitter 83Sr (T(1/2) = 32.4 h, Ebeta+ = 1.23 MeV, Ibeta+ = 24%) is a
      potentially useful radionuclide for therapy planning prior to the use of the
      beta+ emitter 89Sr (T(1/2) = 50.5 d). In order to investigate its production
      possibility, cross section measurements on the 85Rb(p,xn)-reactions, leading to
      the formation of the isotopes (85m,g)Sr, 83Sr, 82Sr and 81Sr, were carried out
      using the stacked-foil technique. In a few cases, the products were separated via
      high-performance liquid chromatography. For 82Sr, both gamma-ray and X-ray
      spectrometry were applied; in other cases only gamma-ray spectrometry was used.
      From the measured excitation functions, the expected yields were calculated. For
      the energy range Ep = 37 --> 30 MeV the 83Sr yield amounts to 160 MBq/microA h
      and the level of the 85gSr (T(1,2) = 64.9 d) and 82Sr (T(1/2) = 25.5 d)
      impurities to <0.25%. In integral tests involving yield measurements
      radiostrontium was chemically separated and its radioactivity determined. The
      experimental production data agreed within 10% with those deduced from the
      excitation functions. The results of the 85Rb(p,3n)83Sr reaction were compared
      with the data on the production of 83Sr via the 82Kr(3He,2n)-process. In the
      energy range E3Hc = 18 --> 10 MeV the theoretical yield of 83Sr amounts to 5
      MBq/microA h and the 82Sr impurity to about 0.2%. The method of choice for the
      production of 83Sr is thus the 85Rb(p,3n)-process, provided a 40 MeV cyclotron is
      available. During this study some supplementary information on the yield and
      purity of 82Sr was also obtained.

PMID- 11993944
TI  - A compact low-energy electron beam irradiator.
AB  - A new compact low-energy electron beam irradiator has been developed. The
      irradiator generates an electron beam to the air with energy variable from 35 to
      80 keV and with a maximum current of 1 mA. The irradiation area is 30 x 30 mm2. A
      special irradiation port is developed for this low-energy irradiator. The
      electron beam is generated from a thermionic LaB6 cathode in vacuum. The beam is
      extracted to the air through a havar foil window. The thickness of the window is
      4.8 microm, it is vacuum-tightly connected to the window to support by an indium
      wire. A controlled bow geometry of the window helps the thin window withstand the
      vacuum pressure. Cold air generated from a vortex tube cools down both the window
      and its support in order to prevent the window from melting down, due to beam
      energy dissipated in the foil. We found that about 60% of the beam current is
      extracted to the air at 80 keV.

PMID- 11993945
TI  - Reliability of two calculation codes for efficiency calibrations of HPGe
      detectors.
AB  - This paper reports the reliability of efficiency calibrations for gamma-ray
      detectors using the calculation codes ANGLE and LabSOCS. For experimental
      verification, three HPGe detectors under various laboratory geometry
      configurations were used for this study. An overall comparison between
      experimental and calculated efficiency calibration curves is presented and
      comments on the various error sources affecting the final results are given. The
      deviations are generally below 10%, which could be acceptable for many
      applications.

PMID- 11993946
TI  - The use of associated particle timing based on the D + D reaction for imaging a
      solid object.
AB  - Associated particle timing based on the D + D reaction has been applied for
      imaging a bulk sample, namely an aluminium box. The relatively low neutron
      energy, 2.8 MeV, allows a better spatial resolution from time-of-flight
      measurements. A combination of a Si detector for charged particles and an NaI(Tl)
      scintillator for inelastic-scatter gamma rays yielded an overall time resolution
      of 0.4 ns, giving a spatial resolution of better than 1 cm. A new reconstruction
      program was developed, yielding an image free from major artefacts.

PMID- 11993947
TI  - Plutonium and other alpha emitters in mushrooms from Poland, Spain and Ukraine.
AB  - The paper presents results on Pu, U and Th isotope activity concentration
      measurements in some mushroom samples collected in Poland, Spain and Ukraine. The
      sampling sites differ a lot with regard to observed levels of Pu, its origin and
      isotope ratios as well as the environmental properties. Some of the Polish
      samples were collected in the northeastern part of the country with up to 30
      Bq/m2 of Chernobyl Pu deposition. Other Polish and the Spanish samples are from
      areas with almost exclusively global fallout Pu present. Ukrainian samples were
      collected in a highly contaminated area with a deposition of about 3.7 kBq/m2 of
      Chernobyl (239-240)Pu. The maximum (239+240)Pu activity concentration was found
      equal to (54+/-4) Bq/kg (dw--dry weight) for a Ukrainian Cantharellus cibarius
      sample. Ukrainian samples have an extremely high radiocesium level, with maximum
      of (51+/-4) MBq/kg (dw). The maximum (239+240)Pu activity concentration for
      Polish samples was (81+/-5) mBq/kg (dw) for Xerocomus badius. From the isotopic
      ratio in this sample it can be concluded that Chernobyl fallout is the origin of
      Pu. More than twice as large was the Spanish maximum for Hebeloma cylindrosporum
      but with only global fallout Pu. Some aspects of the transfer of nuclides to
      fruit bodies is discussed and in some cases the transfer factors or aggregation
      coefficients were calculated. Especially high transfer factors were found for
      Hebeloma cylindrosporum from Spain.

PMID- 11993948
TI  - Cross section measurements for (n, 3n) reactions induced by 14.8 MeV neutrons.
AB  - The cross sections for 209Bi(n, 3n)207Bi, 191Ir(n, 3n)189Ir, 151Eu(n, 3n)149Eu
      and 185Re(n, 3n)183Re reactions were measured by the activation method. The
      experimental results were 12.1+/-1.1, 64.6+/-6.5, 2.7+/-0.4 and 66.0+/-5.6 mb at
      the neutron energy of 14.8+/-0.2 MeV, respectively. The neutron flux was
      determined by the cross section of the 27Al(n, alpha)24Na reaction. The neutron
      energy in these measurements was determined by the method of cross section ratios
      for 90Zr(n, 2n)(89m + g)Zr and 93Nb(n, 2n)92mNb reactions.

PMID- 11993949
TI  - Dynamics of 95Zr in the rice/water/soil system.
AB  - In order to get a better understanding of the environmental behavior of 95Zr and
      to generate fundamental data for evaluation of its ecological risk, an experiment
      was conducted to study 95Zr dynamics in a simulated rice/water/soil system. The
      results showed that the concentration of 95Zr in surface water decreased rapidly
      with time due to precipitation, adsorption to soil and uptake by rice, and most
      of 95Zr in soil was found concentrated in the surface layer (0-8 cm from
      surface). The 95Zr could not readily move downwards with percolating water and
      remained in surface soil. The 95Zr taken up from surface water and surface soil
      mainly concentrated in roots and lower parts of stem. The concentration of 95Zr
      in upper part of stem and leaves were relatively lower, which were only slightly
      greater than the detection limit. The 95Zr concentration in tassel was near the
      detection limit. The dynamics of 95Zr concentrations in rice, water and soil can
      be described with exponential function.

PMID- 11993950
TI  - Determination of uranium concentrations and activity ratios in silicates by alpha
      spectrometry: application to the volcanic rocks from the Trindade and Martin Vaz
      Islands (Brazil).
AB  - A detailed radiochemical procedure for alpha spectrometry measurements of uranium
      concentrations and of 234U/238U activity ratios in silicates is presented. The
      described chemical processing is characterized by relatively high uranium yields,
      in the range of 51-89%. The application of this chemical procedure to geological
      standards allowed estimating a reproducibility of the alpha spectrometry uranium
      measurements on the order of 3.5%. As an application example. the procedure was
      used in the analysis of quaternary volcanic rocks from the Trindade and Martin
      Vaz Islands, Brazil.

PMID- 11993951
TI  - Accumulation and potential dissolution of Chernobyl-derived radionuclides in
      river bottom sediment.
AB  - Areas contaminated with radionuclides from the Chernobyl nuclear accident have
      been identified in Pripyat River near the Chernobyl Nuclear Power Plant. The
      river bottom sediment cores contained 137Cs (10(5)-10(6) Bq/m2) within 0-30 cm
      depth, whose concentration is comparable to that in the ground soil in the
      vicinity of the nuclear power plant (the Exclusion Zone). The sediment cores also
      accumulated 90Sr (10(5) Bq/m2), (239,240)Pu (10(4) Bq/m2) and 241Am (10(4)Bq/m2)
      derived from the accident. Several nuclear fuel particles have been preserved at
      20-25 cm depth that is the peak area of the concentrations of the radionuclides.
      These inventories in the bottom sediments were compared with those of the
      released radionuclides during the accident. An analysis using a selective
      sequential extraction technique was applied for the radionuclides in the
      sediments. Results suggest that the possibility of release of 137Cs and
      (293,240)Pu from the bottom sediment was low compared with 90Sr. The potential
      dissolution and subsequent transport of 90Sr from the river bottom sediment
      should be taken into account with respect to the long-term radiological influence
      on the aquatic environment.

PMID- 11993952
TI  - Tuberous sclerosis complex: a review of neurological aspects.
AB  - Tuberous sclerosis complex is characterized by hamartomatous lesions involving
      skin, brain, kidneys, eyes and heart. Pathologically, tuberous sclerosis is a
      disorder of cell migration, proliferation and differentiation. Cell lineage and
      cell migration disorders in the developing cortex of tuberous sclerosis complex
      patients might produce very different neurological phenotypes including epilepsy,
      cognitive impairment and autism. Cortical tubers constitute the hallmark of the
      disease and are pathognomonic of cerebral tuberous sclerosis. Epilepsy is the
      most common neurological feature, occurring in 96% of patients. Seizures often
      begin in the first months of life and are frequently severe and intractable. The
      treatment of seizures has recently benefited from the advent of the new anti
      epileptic drugs. Selected drug-resistant patients with tuberous sclerosis complex
      could be considered for surgical treatment. Clear localization of the most active
      epileptogenic focus and the zone of the cortical abnormality may lead to
      tuberectomy and improved seizure control in selective drug-resistant patients.
      The finding of multiple areas of cerebral involvement should not automatically
      preclude epilepsy surgery in a child with intractable seizures and a well defined
      seizure origin.

PMID- 11993953
TI  - Ophthalmological abnormalities in children with cerebral white matter disorders.
AB  - The use of magnetic resonance imaging (MRI) in children with severe neurological
      impairment has defined a subgroup with increased T2-signals from cerebral white
      matter. The causes of white matter abnormalities are for the most part unknown,
      despite extensive investigation. Their clinical correlates and characteristics
      have still to be systematically analysed and described. We have compared
      clinical, ophthalmological and electro-ophthalmological findings in such children
      to delineate neurological and MRI patterns and have sought to correlate with the
      progression of disease. Clinical and electro-ophthalmological investigations were
      performed in 26 children with cerebral white matter abnormalities of unknown
      aetiology; 25 of the 26 children showed abnormalities, 23 clinical and 18 electro
      ophthalmological. Optic nerve abnormalities, severe visual impairment and
      strabismus were the most common. Electro-ophthalmological abnormalities were
      increased latencies and abnormal waveform of the visual evoked potentials (VEP).
      Children with progressive disease all had abnormal VEP, whereas none of the ten
      children with a normal VEP deteriorated. We conclude that children with cerebral
      white matter abnormalities almost invariably had ophthalmological and often VEP
      abnormalities. Normal VEP was correlated with non-progressive disorder, as was
      hypoplasia or malformation of the papilla, whereas abnormal VEP were associated
      with progressive disease.

PMID- 11993954
TI  - Mobius sequence--a Swedish multidiscipline study.
AB  - Mobius sequence/syndrome is a rare disorder characterized by congenital palsy of
      the 6th and 7th cranial nerves. Other cranial nerves may be affected, skeletal
      and orofacial anomalies and mental retardation occur. The aims were to determine
      the frequency of associated clinical characteristics and to identify any
      pregnancy or environmental factors in patients with Mobius sequence. A
      prospective study of 25 Swedes with apparent involvement of the 6th and 7th
      cranial nerves was performed and 25 patients, 1 month to 55 years old, were
      examined. Obvious associated systemic anomalies observed included: limb
      malformations (10), Poland anomaly (2), hypodontia (7), microglossia (6), cleft
      palate (4), hearing impairment (5) and external ear malformation (1). Pronounced
      functional abnormalities were observed involving facial expression (16), speech
      (13), eating and swallowing (12) and difficulty in sucking in infancy (11). Six
      patients had an autistic syndrome, one an autistic-like condition, and mental
      retardation was found in all these patients. No common aetiological cause was
      found but their mothers' pregnancy histories revealed a history of
      benzodiazepines (1), bleeding during pregnancy (8), spontaneous abortion (7) and
      chorion villus sampling in the second month of pregnancy (1). In conclusion, many
      patients had multiple problems with eating and communication resulting from
      facial palsy, cleft palate and tongue anomalies. Autism and mental retardation
      was diagnosed in one-third of the patients. Awareness of the wide spectrum of
      manifestations in Mobius sequence will assist in identification of the associated
      malformations and functional problems that are often seen and result in better
      care of the children.

PMID- 11993955
TI  - Auditory event-related brain potentials in children with specific language
      impairment.
AB  - Event-related brain potentials evoked by tone and speech stimuli were recorded in
      ten children with specific language impairment and a control group. The patient
      group showed prolonged P3 latencies in both tasks compared with the controls and
      smaller P3 amplitude in the speech task. There were no group differences
      concerning the N1-P2 components. The findings indicate that the children with
      language impairment showed signs of deficient late-stage auditory perceptual
      processing whereas the earlier sensory stages as indexed by the N1 were no
      different from the controls. The results are further discussed within the
      framework of context updating in working memory.

PMID- 11993956
TI  - What's new in neuroimaging? Magnetic resonance imaging of the immature brain.

PMID- 11993957
TI  - Joubert syndrome with associated corpus callosum agenesis.
AB  - In 1969, Joubert et al. studied a family where four of six children had a severe
      clinical condition with episodic alternate hyperpnoea and apnoea, hypotonia,
      ataxia, psychomotor delay, and abnormal ocular movements. Two of the four had
      agenesis of the posterior-inferior part of the cerebellar vermis and two had
      complete agenesis of the vermis. We report a 5-month-old girl with Joubert
      syndrome in whom MRI shows both features typical of this condition and associated
      corpus callosum agenesis. To our knowledge, complete callosal agenesis has been
      infrequently reported in children with Joubert syndrome; consequently, it might
      be regarded as a casual finding. Nevertheless, the hypothesis of a developmental
      abnormality of midline structures extended to the supratentorial compartment is
      rather attractive.

PMID- 11993958
TI  - Rasmussen syndrome of chronic focal encephalitis.
AB  - Rasmussen syndrome of chronic focal encephalitis is a relatively rare disease,
      which presents with epilepsia partialis continua and hemiparesis in childhood.
      Though first described in the 1950s it still remains somewhat of an enigma. The
      immunological process involved in its pathogenesis is better understood now but
      the exact relationship to viral infections is still unclear. Medical treatment
      remains disappointing while results of surgical treatment are mixed. There are
      emerging insights into the disease, which are reviewed and a case study of a
      patient with Rasmussen syndrome is presented.

PMID- 11993959
TI  - Polymicrogyria in chromosome 22q11 deletion syndrome.
AB  - Central nervous system (CNS) dysfunction is a cardinal feature in 22q11 deletion.
      The underlying CNS abnormalities remain, however, unknown. We report unilateral
      hemispheric polymicrogyria in a child with 22q11 deletion presenting with
      hemiplegia and cognitive and behavioural disorders. This observation widens the
      spectrum of brain malformations associated with this genetic defect. It further
      suggests a relationship between the 22q11 deletion and disorders of cerebral
      gyration. It would therefore be interesting to look for neuronal migration
      disorders in patients with 22q11 deletion presenting neurological signs, and on
      the other hand to screen for 22q11 deletion in patients with isolated neuronal
      migration disorders.

PMID- 11993960
TI  - Gene table: congenital muscular dystrophies.

PMID- 11993961
TI  - Basic statistics of PM2.5 and PM10 in the atmosphere of Mexico City.
AB  - The high levels of fine particulate matter in Mexico City are of concern since
      they may induce severe public health effects as well as the attenuation of
      visible light. Sequential filter samplers were used at six different sites from
      23 February to 22 March 1997. The sampling campaign was carried out as part of
      the project 'Investigacion sobre Materia Particulada y Deterioro Atmosferico
      Aerosol and Visibility Evaluation Research'. This research was a cooperative
      project sponsored by PEMEX and by the US Department of Energy. Sampling sites
      represent the different land uses along the city, the northwest station,
      Tlalnepantla, is located in a mixed medium income residential and industrial
      area. The northeast station, Xalostoc, is located in a highly industrialized
      area, Netzahualcoyotl is located in a mixed land use area, mainly commercial and
      residential. Station La Merced is located in the commercial and administrative
      district downtown. The southwest station is located in the Pedregal de San Angel,
      in a high-income neighborhood, and the southeast station located in Cerro de la
      Estrella is a mixed medium income residential and commercial area. Samples were
      collected four times a day in Cerro de la Estrella (CES), La Merced (MER) and
      Xalostoc (XAL) with sampling periods of 6 h. In Pedregal (PED), Tlalnepantla
      (TLA) and Netzahualcoyot1 (NEZ) sampling periods were every 24 h. In this paper
      the basic statistics of PM2.5 and PM10 mass concentrations are presented. The
      average results showed that 49, 61, 46, 57, 51 and 44% of the PM10 consisted of
      PM2.5 for CES, MER, XAL, PED, TLA and NEZ, respectively. The 24-h average highest
      concentrations of PM25 and PM10 were registered at NEZ (184 and 267 microg/m3)
      and the lowest at PED (22 and 39 microg/m3). The highest PM10 correlations were
      between XAL-CES (0.79), PED-TLA (0.80). In contrast, the highest PM2.5
      correlations were between CES-PED (0.74), MER-CES (0.73) and TLA-PED (0.72),
      showing a lower correlation than the PM10 one. The results of the PM10 from 12.00
      to 18.00 h at CES and MER presented the highest variability and also the highest
      median concentrations, meanwhile XAL showed them from 06.00 to 12.00 h. The
      highest variability and median concentrations of PM2.5 were from 06.00 to 12.00 h
      for the three stations.

PMID- 11993962
TI  - Chemical composition of PM2.5 and PM10 in Mexico City during winter 1997.
AB  - PM2.5 and PM10 were measured over 24-h intervals at six core sites and at 25
      satellite sites in and around Mexico City from 23 February to 22 March 1997. In
      addition, four 6-h samples were taken each day at three of the core sites.
      Sampling locations were selected to represent regional, central city, commercial,
      residential, and industrial portions of the city. Mass and light transmission
      concentrations were determined on all of the samples, while elements, ions and
      carbon were measured on approximately two-thirds of the samples. PM10
      concentrations were highly variable, with almost three-fold differences between
      the highest and lowest concentrations. Fugitive dust was the major cause of PM10
      differences, although carbon concentrations were also highly variable among the
      sampling sites. Approximately 50% of PM10 was in the PM2.5 fraction. The majority
      of PM mass was comprised of carbon, sulfate, nitrate, ammonium and crustal
      components, but in different proportions on different days and at different
      sites. The largest fine-particle components were carbonaceous aerosols,
      constituting approximately 50% of PM2.5 mass, followed by approximately 30%
      secondary inorganic aerosols and approximately 15% geological material.
      Geological material is the largest component of PM10, constituting approximately
      50% of PM10 mass, followed by approximately 32% carbonaceous aerosols and
      approximately 17% secondary inorganic aerosols. Sulfate concentrations were twice
      as high as nitrate concentrations. Sulfate and nitrate were present as ammonium
      sulfate and ammonium nitrate. Approximately two-thirds of the ammonium sulfate
      measured in urban areas appears to have been transported from regions outside of
      the study domain, rather than formed from emissions in the urban area. Diurnal
      variations are apparent, with two-fold increases in concentration from night-time
      to daytime. Morning samples had the highest PM2.5 and PM10 mass, secondary
      inorganic aerosols and carbon concentrations, probably due to a shallow surface
      inversion and rush-hour traffic.

PMID- 11993963
TI  - Observations of formic and acetic acids at three sites of Mexico City.
AB  - Levels of atmospheric carboxylic acids in gas and particulate matter were
      measured at three sites in Mexico City within the month of March 2000. An annular
      denuder system was used for sampling and the analytical method was HPLC with UV
      detection. Formic and acetic acids were present in the PM2.5 fraction and in the
      gas phase. Total concentration of formic acid was between 0 and 7 ppbV and total
      concentration of acetic acid was between 1 and 17 ppbV. On average 53% of the
      formic acid and 67% of the acetic acid were present in particulate matter.

PMID- 11993964
TI  - Aerosol impacts on visible light extinction in the atmosphere of Mexico City.
AB  - Eleven diurnal aerosol visible light absorption and scattering patterns were
      obtained from measurements done with an aethalometer and an integrating
      nephelometer during 28 February-10 March 1997 at two different sites in the
      Mexico City basin. Both measurement sites, the Merced site affected by regional
      and urban-scale aerosol and the Pedregal site dominated by regional-scale
      aerosol, showed a variety of diurnal light absorption and scattering patterns.
      For the majority of the 11 studied days, the highest absorption peaks appeared in
      the early morning, 07.00-09.30 h while those of scattering appeared later, 09.30
      11.00 h. The earlier absorption peaks could be attributed to the elevated
      elemental carbon vehicular emissions during the heavy traffic hours whereas the
      later scattering peaks could be attributed to secondary aerosols formed
      photochemically in the atmosphere. During the period examined, the Pedregal site
      exhibited on the average a lower aerosol scattering and a higher aerosol
      absorption contribution to the total aerosol visible light extinction and a
      better visibility than that of the Merced site. Hence, the impact of aerosol
      absorption on the visibility degradation due to aerosols was greater at the less
      hazy Pedregal site. The overall 11-day aerosol visibility average of 20.9 km
      found at La Merced site, was only 9.4 km lower than that of 30.3 km found at the
      Pedregal site. This small aerosol visibility difference, of the order of the
      standard deviation, led to the conclusion that besides the regional-scale aerosol
      impact, the urban-scale aerosol impact on aerosol visible light extinction is
      very similar at La Merced and Pedregal sites.

PMID- 11993965
TI  - Light extinction by fine atmospheric particles in the White Mountains region of
      New Hampshire and its relationship to air mass transport.
AB  - Chemical, optical, and physical measurements of fine aerosols (aerodynamic
      diameter < or = 2.5 microm) have been performed at a mountaintop location
      adjacent to the White Mountain National Forest in northern NH, USA. A 1-month
      long sampling campaign was conducted at Cranmore Mountain during spring 2000. We
      report on the apportionment of light extinction by fine aerosols into its major
      chemical components, and relationships between variations in aerosol parameters
      and changes in air mass origin. Filter-based, 24-h integrated samples were
      collected and analyzed for major inorganic ions, as well as organic (OC),
      elemental (EC), and total carbon. Light scattering and light absorption
      coefficients were measured at 5-min intervals using an integrating nephelometer
      and a light absorption photometer. Fine particle number density was measured with
      a condensation particle counter. Air mass origins and transport patterns were
      investigated through the use of 3-day backward trajectories and a synoptic
      climate classification system. Two distinct transport regimes were observed: (1)
      flow from the north/northeast (N/NE) occurred during 9 out of 18 sample-days; and
      (2) flow from the west/southwest (W/SW) occurred 8 out of 18 sample-days. All
      measured and derived aerosol and meteorological parameters were separated into
      two categories based on these different flow scenarios. During W/SW flow, higher
      values of aerosol chemical concentration, absorption and scattering coefficients,
      number density, and haziness were observed compared to N/NE flow. The highest
      level of haziness was associated with the climate classification Frontal Atlantic
      Return, which brought polluted air into the region from the mid-Atlantic
      corridor. Fine particle mass scattering efficiencies of (NH4)2SO4 and OC were
      5.35 +/- 0.42 m2 g(-1) and 1.56 +/- 0.40 m2 g(-1), respectively, when transport
      was out of the N/NE. When transport was from the W/SW the values were 4.94 +/-
      0.68 m2 g(-1) for (NH4)2SO4 and 2.18 +/- 0.91 m2 g(-1) for OC. EC mass absorption
      efficiency when transport was from the N/NE was 9.66 +/- 1.06 m2 g(-1) and 10.80
      +/- 1.76 m2 g(-1) when transport was from the W/SW. Results from this work can be
      used to predict visual air quality in the White Mountain National Forest based on
      a forecasted synoptic climate classification and its associated visibility.

PMID- 11993966
TI  - Personal exposure to benzene, toluene and xylene in different microenvironments
      at the Mexico City metropolitan zone.
AB  - The Mexico City Metropolitan Zone (ZMCM) population's exposure to benzene,
      toluene and xylene was measured at different microenvironments to establish basic
      indicators of the presence and effects of these characteristic volatile organic
      compounds (VOC). In particular, VOC personal exposures were measured in different
      microenvironments during a 5-day working week, with 12-h daily periods. We have
      found a good agreement of our results with the registered VOC levels of the
      Metropolitan Automated Monitor System (RAMA) for the corresponding period. From
      our results, we expect to generate useful information to evaluate the health
      effects of these VOCs on exposed people.

PMID- 11993967
TI  - Measurements of children's exposures to particles and nitrogen dioxide in
      Santiago, Chile.
AB  - An exposure study of children (aged 10-12 years) living in Santiago, Chile, was
      conducted. Personal, indoor and outdoor fine and inhalable particulate matter (<
      2.5 .m in diameter, PM2.5 and < 10 microm in diameter, PM10, respectively), and
      nitrogen dioxide (NO2) were measured during pilot (N = 8) and main (N = 20)
      studies, which were conducted during the winters of 1998 and 1999, respectively.
      For the main study, personal, indoor and outdoor 24-h samples were collected for
      five consecutive days. Similar mean personal, indoor and outdoor PM2.5
      concentrations (69.5, 68.5 and 68.1 microg/m3, respectively) were found. However,
      for coarse particles (calculated as the difference between measured PM10 and
      PM2.5, PM2.5-10), indoor and outdoor levels (35.4 and 47.4 microg/m3) were lower
      than their corresponding personal exposures (76.3 microg/m3). Indoor and outdoor
      NO2 concentrations were comparable (35.8 and 36.9 ppb) and higher than personal
      exposures (25.9 ppb). Very low ambient indoor and personal O3 levels were found,
      which were mostly below the method's limit of detection (LOD). Outdoor particles
      contributed significantly to indoor concentrations, with effective penetration
      efficiencies of 0.61 and 0.30 for PM2.5 and PM2.5-10, respectively. Personal
      exposures were strongly associated with indoor and outdoor concentrations for
      PM2.5, but weakly associated for PM2.5-10. For NO2, weak associations were
      obtained for indoor-outdoor and personal-outdoor relationships. This is probably
      a result of the presence of gas cooking stoves in all the homes. Median I/O, P/I
      and P/O ratios for PM2.5 were close to unity, and for NO2 they ranged between
      0.64 and 0.95. These ratios were probably due to high ambient PM2.5 and NO2
      levels in Santiago, which diminished the relative contribution of indoor sources
      and subjects' activities to indoor and personal PM2.5 and NO2 levels.

PMID- 11993968
TI  - Resuspension of coal and coal/municipal sewage sludge combustion generated fine
      particles for inhalation health effects studies.
AB  - Airborne particulate matter (PM) is an important environmental issue because of
      its association with acute respiratory distress in humans, although the specific
      particle characteristics that cause lung damage have yet to be identified.
      Particle size, acid aerosols, water-soluble transition metals (e.g. Cu, Fe, V, Ni
      and Zn), polyaromatic hydrocarbons, and particle composition are the focus of
      several popular hypotheses addressing respiratory distress. All of the above
      mentioned characteristics are contained in PM generated from the combustion of
      both pulverized coal, and biomass, including dried municipal sewage sludge (MSS).
      In this investigation, we report results from collaborative interdisciplinary
      research on the inhalation health risks caused by particles emitted from the co
      combustion of municipal sewage sludge (MSS) and coal. A solid particle
      resuspension system was implemented to resuspend ash particles. Mice were exposed
      to resuspended coal and MSS/coal ash particles. Mice exposed to MSS/coal ash
      particulate demonstrated significant increases in lung permeability, a marker of
      the early stages of pathological lung injury, while the mice exposed to coal-only
      ash did not. These results show that the composition of particles actually
      inhaled is important in determining lung damage. Zinc was significantly more
      concentrated in the MSS/coal ash than coal ash particles and the pH of these
      particles did not differ significantly. Specifically, an MSS/coal mixture, when
      burned, emits particles that may cause significantly more lung damage than coal
      alone, and that consequently, the use of MSS as a 'green', CO2-neutral
      replacement fuel should be carefully considered.

PMID- 11993969
TI  - Medicines, transplants and practice standards.

PMID- 11993970
TI  - Rabies antibody testing and the UK Pet Travel Scheme.
AB  - The Pet Travel Scheme (PETS) commenced on February 28, 2000, allowing pet dogs
      and cats from named countries to enter the UK without spending six months in
      quarantine as long as they met specific criteria. Since the start of the scheme
      to the end of February 2002, more than 45,000 animals have successfully entered
      the UK under PETS. In this article, Dr Tony Fooks and colleagues consider the
      results of serological testing under the scheme at the Veterinary Laboratories
      Agency and look to future developments.

PMID- 11993971
TI  - Differentiation of dogs with regenerative and non-regenerative anaemia on the
      basis of their red cell distribution width and mean corpuscular volume.
AB  - The red blood cell distribution width (RDW), which provides a quantitative
      measure of the heterogeneity of the red cell population (anisocytosis) in the
      peripheral blood, the mean corpuscular volume (MCV) and a regression model
      combining both variables were used to assess their predictive accuracy in
      differentiating 51 dogs with regenerative anaemia from 92 dogs with non
      regenerative anaemia, which had been diagnosed on the basis of the corrected
      reticulocyte count A classification tree analysis was constructed to generate an
      optimum set of diagnostic rules to differentiate between the two types of
      anaemia. Seventy-four dogs with a normal haemogram were used as controls. An
      increase of 1 per cent in the RDW and of 1 fl in the MCV increased the odds of an
      anaemic dog suffering from regenerative anaemia by factors of 1.3 and 1.14,
      respectively. By the classification tree, 78 per cent of anaemic dogs with a RDW
      of 16.25 per cent or less would be expected to have non-regenerative anaemia.
      With a RDW over 16.25 per cent, an MCV of 68.2 fl was the cut-off between dogs
      expected to have regenerative (71 per cent) or non-regenerative (75 per cent)
      anaemia. The RDW and MCV are measured by most automatic haematology analysers and
      may give the first indication of the bone marrow response of an anaemic dog.
      However, different electronic counters give different normal values of the RDW
      and MCV.

PMID- 11993972
TI  - Relationship between aggressive and avoidance behaviour by dogs and their
      experience in the first six months of life.
AB  - The early experiences of dogs showing signs of avoidance behaviour or aggression
      were compared with those of dogs from the same clinical population that did not
      show such behaviour. The occurrence of each behavioural sign was tested for its
      association with the dog's maternal environment, the environment it experienced
      between three and six months of age, and the age at which it had been acquired.
      Non-domestic maternal environments, and a lack of experience of urban
      environments between three and six months of age, were both significantly
      associated with aggression towards unfamiliar people and avoidance behaviour.
      Aggression during a veterinary examination was more likely in dogs from non
      domestic maternal environments. There was no significant association with either
      environment for aggression towards familiar people, or towards dogs.

PMID- 11993973
TI  - Studies of the efficacy of a novel intranasal vaccine against feline
      bordetellosis.
AB  - A novel intranasal vaccine against disease caused by Bordetella bronchiseptica in
      cats was tested in a series of three experiments. In the first experiment a
      vaccinated group and an unvaccinated control group of kittens were challenged by
      the aerosol route with virulent B bronchiseptica three weeks after they had been
      vaccinated. The control kittens developed upper respiratory tract signs typical
      of feline B bronchiseptica infection, including rhinitis, a serous ocular and
      nasal discharge, fever, sneezing and coughing. The mean (sd) clinical score for
      the cats in the unvaccinated control group was 19.5 (5.4) compared with 1.53
      (1.9) for the vaccinated group. In the second experiment vaccinated kittens were
      challenged with virulent B bronchiseptica 72 hours after they were vaccinated.
      Their mean clinical score was 2.76 (2.62) compared with 13.4 (3.33) for the
      control group. In the final experiment, vaccinated and unvaccinated control cats
      were challenged after six or 12 months. After six months the mean clinical scores
      were 13.9 (4.7) for the control group, compared with 1.33 (1.56) for the
      vaccinated group, and after 12 months the scores were 9.92 (5.79) for the control
      group compared with 0.92 (0.89) for the vaccinated group.

PMID- 11993974
TI  - Radiographic, computed tomographic and arthroscopic findings in 23 dogs with
      osteochondrosis of the tarsocrural joint.
AB  - Twenty-three dogs with osteochondrosis of the tarsocrural joint were evaluated by
      radiography, computed tomography (CT) and arthroscopy. The radiographic
      examination included an extended and flexed mediolateral, a plantarodorsal, a
      flexed dorsoplantar skyline view, and a plantaromedial-dorsolateral and a
      plantarolateral-dorsomedial view (two oblique views). The CT examination was
      carried out in ventral recumbency and 1 mm slices were taken with a bone window
      setting; 31 lesions were identified in the 46 joints examined. The arthroscopic
      exploration used either a plantar or a dorsal puncture, depending on the site of
      the lesion. In six cases the lateral, and in 17 cases the medial trochlear ridge
      was involved. Although the survey radiographs were sufficient to make a
      diagnosis, the CT examination helped to determine the exact site, and the number
      and size of the fragments of bone. A four-stage classification system comparable
      to the one used in man was established. Arthroscopy provided information about
      synovial inflammation and damage to the joint cartilage, and made it possible to
      remove fragments of bone from one-third of the cases.

PMID- 11993975
TI  - Intradermal test reactivity to Malassezia pachydermatis in atopic dogs.

PMID- 11993976
TI  - Timing of oestrus and reproductive behaviour in Indian street dogs.

PMID- 11993977
TI  - Detection and isolation of an iridovirus from chameleons (Chamaeleo quadricornis
      and Chamaeleo hoehnelli) in the United Kingdom.

PMID- 11993978
TI  - National movement restrictions and FMD.

PMID- 11993979
TI  - Need for vigilance in the aftermath of FMD and CSF.

PMID- 11993980
TI  - Holiday pay for TVIs.

PMID- 11993981
TI  - Maedi-visna and biosecurity.

PMID- 11993982
TI  - Veterinary nurse training.

PMID- 11993983
TI  - Veterinary nurse training.

PMID- 11993984
TI  - Future of the RCVS library.

PMID- 11993985
TI  - Aspirin treatment of postvaccinal hypertrophic osteodystrophy in a weimaraner
      puppy.

PMID- 11993986
TI  - Sources of information on PMWS/PDNS.

PMID- 11993987
TI  - The many tales of a tail: carboxyl-terminal tail heterogeneity specializes
      histone H2A variants for defined chromatin function.
AB  - For many years, histones were considered to be passive structural components of
      eukaryotic chromatin. Experimental evidence that has accumulated during the past
      few years indicates that in addition to their structural role, histones play a
      very important functional role and that they can operate as epigenetic markers.
      This notion has rekindled the interest in histone variants and their
      participation in the processes of chromatin activation and inactivation. Recent
      papers have focused their attention on histone H2A variants. The variants of this
      overlooked histone participate in many biological processes ranging from
      transcriptional activation to DNA repair, meiosis, and apoptosis. A nucleosome
      containing at least one of these variants has been crystallized and biophysically
      characterized in solution. From all these results, a new concept has started to
      emerge, which supports the notion that the functional roles of H2A variants are
      exerted through alterations in chromatin stability and folding that result from
      the structural variation at the carboxyl-terminal end of this histone.

PMID- 11993988
TI  - Atomic force microscopic measurement of the interdomain angle in symmetric
      Holliday junctions.
AB  - The Holliday junction is a key intermediate in genetic recombination. It consists
      of four DNA strands that associate by base pairing to produce four double helices
      flanking a junction point. In the presence of multivalent cations, the four
      helices, in turn, stack in pairs to form two double-helical domains. The angle
      between these domains has been shown in a number of solution studies to be
      approximately 60 degrees in junctions flanked by asymmetric sequences. However,
      the recently determined crystal structure of a symmetric junction [Eichman, B.
      F., Vargason, J. M., Mooers, B. H. M., and Ho, P. S. (2000) Proc. Natl. Acad.
      Sci. U.S.A. 97, 3971-3976] finds an angle closer to 40 degrees, possibly because
      of sequence effects. From the crystal structure alone, one cannot exclude the
      possibility that this unusual angle is a consequence of crystal packing effects.
      We have formed two-dimensional (2D) periodic arrays of DNA parallelograms with
      the same junction-flanking sequence used to produce the crystals; these
      parallelograms are free to adopt their preferred interdomain angle. Atomic force
      microscopy can be used to establish the interdomain angle in this system. We find
      that the angle in this junction is 43 degrees, in good agreement with the results
      of crystallography. We have used hydroxyl radical autofootprinting to establish
      that the branch point is at the same migratory position seen in the crystals.

PMID- 11993989
TI  - Solution structure of the Vam7p PX domain.
AB  - PX domains have been recently found to act as phosphoinositide binding modules.
      In the yeast SNARE protein Vam7p, the PX domain binds to PtdIns(3)P and is
      required for vacuolar targeting. To gain insight into how PX domains function,
      the solution structure of the ligand-free Vam7p PX domain has been determined by
      NMR spectroscopy. The Vam7p PX domain has the same overall alpha/beta fold
      observed in the structures of the ligand-free p47(phox) PX domain and the
      PtdIns(3)P-bound p40(phox) PX domain, exhibiting several similarities and
      differences with these two PX domains. Most striking is the similarity between
      the Vam7p and p40(phox) PX domains in a subset of secondary structure elements
      despite the low level of sequence identity between them, suggesting that these
      elements form a conserved core in the PX domain fold. These similarities and the
      observation that a putative PtdIns(3)P binding site is already formed in the apo
      Vam7p PX domains suggest that ligand binding does not induce major conformational
      changes, contrary to what was previously thought. The proposed ligand binding
      site of the Vam7p PX domain includes basic side chains from the conserved
      structural core that also participate in PtdIns(3)P binding to the p40(phox) PX
      domain, and basic side chains from a variable loop that probably inserts into the
      membrane. These results indicate that PX domains contain a combination of
      conserved and variable features that allow them to have a common function and at
      the same time exhibit distinct specificities, mechanisms of regulation, or modes
      of interaction with effector molecules.

PMID- 11993990
TI  - Formation of a trypsin-borate-4-aminobutanol ternary complex.
AB  - The formation of ternary complexes involving serine proteases, borate, and an
      alcohol has important implications for understanding the physiological actions of
      borate and for the development of tight binding inhibitors for this class of
      enzymes. Recent studies of a related enzyme, gamma-glutamyl transpeptidase, which
      is subject to inhibition by a labile serine/borate mixture, have demonstrated
      that construction of a non-labile boronate analogue results in an inhibitor with
      nearly 10(5)-fold greater potency. To evaluate the generalization of this
      biochemistry to serine proteases, we have observed the ternary complex formed
      from 4-aminobutanol, borate, and trypsin. A combination of (11)B and (1)H NMR and
      spectrophotometric assays using acetylarginine p-nitroanilide (Ac-Arg-pNA) as the
      chromogenic substrate all indicate a cooperative binding interaction in which the
      borate is esterified by the oxygen atoms of the 4-aminobutanol and trypsin
      residue Ser(195). Two downfield-shifted proton resonances at 15.5 and 16.6 ppm
      are proposed to arise from the labile imidazolium protons on His(57), indicating
      a salt bridge interaction with the negatively charged borate. A cooperativity
      parameter alpha of 0.2 is derived from the assays. These results provide the
      first direct evidence for formation of a ternary complex involving a serine
      protease, borate, and an alcohol, and suggest that this represents a general
      approach for the development of tight binding ligands.

PMID- 11993991
TI  - Phosphorylation and flexibility of cyclic-AMP-dependent protein kinase (PKA)
      using (31)P NMR spectroscopy.
AB  - Cell signaling pathways rely on phosphotransfer reactions that are catalyzed by
      protein kinases. The protein kinases themselves are typically regulated by
      phosphorylation and concurrent structural rearrangements, both near the catalytic
      site and elsewhere. Thus, physiological function requires posttranslational
      modification and deformable structures. A prototypical example is provided by
      cyclic AMP-dependent protein kinase (PKA). It is activated by phosphorylation, is
      inhomogeneously phosphorylated when expressed in bacteria, and exhibits a wide
      range of dynamic properties. Here we use (31)P nuclear magnetic resonance (NMR)
      spectroscopy to characterize the phosphorylation states and to estimate the
      flexibility of the phosphorylation sites of 2-, 3-, and 4-fold phosphorylated
      PKA. The phosphorylation sites Ser10, Ser139, Thr197, and Ser338 are assigned to
      individual NMR resonances, assisted by complexation with AMP-PNP and
      dephosphorylation with alkaline phosphatase. Rotational diffusion correlation
      times estimated from resonance line widths show progressively increasing
      flexibilities for phosphothreonine 197, phosphoserines 139 and 338, and disorder
      at phosphoserine 10, consistent with crystal structures of PKA. However, because
      the apparent rotational diffusion correlation time fitted for phosphothreonine
      197 of the activation loop is longer than the overall PKA rotational diffusion
      time, microsecond to millisecond time scale conformational exchange effects
      involving motions of phosphothreonine 197 are probable. These may represent
      "open"-"closed" transitions of the uncomplexed protein in solution. These data
      represent direct measurements of flexibilities also associated with functional
      properties, such as ATP binding and membrane association, and illustrate the
      applicability of (31)P NMR for functional and dynamic characterization of protein
      kinase phosphorylation sites.

PMID- 11993992
TI  - Comparison of functional domains in vertebrate-type ferredoxins.
AB  - The vertebrate-type Cys(4)Fe(2)S(2) ferredoxins are a class of small acidic
      proteins that typically act as electron shuttles between NAD(P)H-dependent
      reductases and monoxygenases, particularly cytochromes P450. Nuclear magnetic
      resonance assignments and detailed analysis of nuclear Overhauser effects permit
      the direct comparison of the functional C-terminal domains of three vertebrate
      type ferredoxins, the mammalian adrenodoxin (Adx) and the bacterial ferredoxins
      putidaredoxin (Pdx) and terpredoxin (Tdx). In particular, homologous hydrogen
      bonding networks involving a conserved basic residue (His 49 in Pdx, His 56 in
      Adx, Arg 49 in Tdx) are detailed. This hydrogen bond network appears to play a
      role in the mechanical transmission of redox-dependent conformational and dynamic
      changes from the iron-sulfur binding loop to the C-terminal domain.
      Hydrogen/deuterium exchange measurements have been made in Adx as a function of
      oxidation state for comparison with previous studies of Pdx and Tdx. The results
      of these measurements highlight the importance of the conserved basic residue in
      the linkage between oxidation state and protein dynamics. Finally, a series of
      mutations have been made in the C-terminal domain of Pdx, including one, Y51F,
      that disrupts the proposed hydrogen-bonding network without perturbing steric and
      hydrophobic interactions in the functional domain. Although the mutant is
      considerably destabilized with respect to wild-type Pdx, relatively unperturbed
      chemical shifts for residues near the site of the mutation and NOEs between water
      and Phe 51 suggest that the network is reconstituted with a solvent water in
      place of the tyrosine hydroxyl group in this mutant.

PMID- 11993993
TI  - GXXXG and AXXXA: common alpha-helical interaction motifs in proteins,
      particularly in extremophiles.
AB  - The GXXXG motif is a frequently occurring sequence of residues that is known to
      favor helix-helix interactions in membrane proteins. Here we show that the GXXXG
      motif is also prevalent in soluble proteins whose structures have been
      determined. Some 152 proteins from a non-redundant PDB set contain at least one
      alpha-helix with the GXXXG motif, 41 +/- 9% more than expected if glycine
      residues were uniformly distributed in those alpha-helices. More than 50% of the
      GXXXG-containing alpha-helices participate in helix-helix interactions. In fact,
      26 of those helix-helix interactions are structurally similar to the helix-helix
      interaction of the glycophorin A dimer, where two transmembrane helices associate
      to form a dimer stabilized by the GXXXG motif. As for the glycophorin A
      structure, we find backbone-to-backbone atomic contacts of the C alpha-H...O type
      in each of these 26 helix-helix interactions that display the stereochemical
      hallmarks of hydrogen bond formation. These glycophorin A-like helix-helix
      interactions are enriched in the general set of helix-helix interactions
      containing the GXXXG motif, suggesting that the inferred C alpha-H...O hydrogen
      bonds stabilize the helix-helix interactions. In addition to the GXXXG motif,
      some 808 proteins from the non-redundant PDB set contain at least one alpha-helix
      with the AXXXA motif (30 +/- 3% greater than expected). Both the GXXXG and AXXXA
      motifs occur frequently in predicted alpha-helices from 24 fully sequenced
      genomes. Occurrence of the AXXXA motif is enhanced to a greater extent in
      thermophiles than in mesophiles, suggesting that helical interaction based on the
      AXXXA motif may be a common mechanism of thermostability in protein structures.
      We conclude that the GXXXG sequence motif stabilizes helix-helix interactions in
      proteins, and that the AXXXA sequence motif also stabilizes the folded state of
      proteins.

PMID- 11993994
TI  - The structure of a mutant photosynthetic reaction center shows unexpected changes
      in main chain orientations and quinone position.
AB  - We report on the unexpected structural changes caused by substitution of acidic
      amino acids in the Q(B) binding pocket of the bacterial photosynthetic reaction
      center by alanines. The mutations targeted key residues L212Glu and L213Asp of
      this transmembrane protein-cofactor complex. The amino acid substitutions in the
      L212Ala-L213Ala mutant reaction center ("AA") were known to affect the delivery
      of protons after the light-induced generation of Q(B)(-), which renders the AA
      strain incapable of photosynthetic growth. The AA structure not only revealed
      side chain rearrangements but also showed movement of the main chain segments
      that are contiguous with the mutation sites. The alanine substitutions caused an
      expansion of the cavity rather than its collapse. In addition, Q(B) is found
      mainly in the binding site that is proximal to the iron-ligand complex (closest
      to Q(A)) as opposed to its distal binding site (furthest from Q(A)) in the
      structure of the wild-type reaction center. The observed rearrangements in the
      structure of the AA reaction center establish a new balance between charged
      residues of an interactive network near Q(B). This structurally and
      electrostatically altered complex forms the basis for future understanding of the
      structural basis for proton transfer in active reaction centers which retain the
      alanine substitutions but carry a distant compensatory mutation.

PMID- 11993995
TI  - An insight into the mechanism of inhibition and reactivation of the F(1)-ATPases
      by tentoxin.
AB  - The mechanism of inhibition and reactivation of chloroplast ATP-synthase by the
      fungal cyclotetrapeptide tentoxin was investigated by photolabeling experiments,
      binding studies, and kinetic analysis using synthetic analogues of tentoxin. The
      alpha-subunit of chloroplast F(1)-ATPase (CF(1)) was specifically labeled by a
      photoactivatable tentoxin derivative, providing the first direct evidence of
      tentoxin binding to the alpha-subunit, and 3D homology modeling was used to
      locate tentoxin in its putative binding site at the alpha/beta interface. The non
      photosynthetic F(1)-ATPase from thermophilic bacterium (TF(1)) proved to be also
      tentoxin-sensitive, and enzyme turnover dramatically increased the rate of
      tentoxin binding to its inhibitory site, contrary to what was previously observed
      with epsilon-depleted CF(1) [Santolini, J., Haraux, F., Sigalat, C., Moal, G.,
      and Andre, F. (1999) J. Biol. Chem. 274, 849-858]. We propose that tentoxin
      preferentially binds to an ADP-loaded alpha beta pair, and mechanically blocks
      the catalytic cycle, perhaps by the impossibility of converting this alpha beta
      pair into an ATP-loaded alpha beta pair. Using (14)C-tentoxin and selected
      synthetic analogues, we found that toxin binding to the tight inhibitory site of
      CF(1) exerts some cooperative effect on the loose reactivatory site, but that no
      reciprocal effect exists. When the two tentoxin-binding sites are filled in
      reactivated F(1)-ATPase, they do not exchange their role during catalytic
      turnover, indicating an impairment between nucleotide occupancy and the shape of
      tentoxin-binding pocket. This analysis provides a mechanical interpretation of
      the inhibition of F(1)-ATPase by tentoxin and a clue for understanding the
      reactivation process.

PMID- 11993996
TI  - Spectral tuning and evolution of short wave-sensitive cone pigments in cottoid
      fish from Lake Baikal.
AB  - The cottoid fishes of Lake Baikal in eastern Siberia provide a unique opportunity
      to study the evolution of visual pigments in a group of closely related species
      exposed to different photic environments. Members of this species flock are
      adapted to different depth habitats down to >1000 m, and both the rod and cone
      visual pigments display short wave shifts as depth increases. The blue-sensitive
      cone pigments of the SWS2 class cluster into two species groups with lambda(max)
      values of 450 and 430 nm, with the pigment in Cottus gobio, a cottoid fish native
      to Britain, forming a third group with a lambda(max) of 467 nm. The sequences of
      the SWS2 opsin gene from C. gobio and from two representatives of the 450 and 430
      nm Baikal groups are presented. Approximately 6 nm of the spectral difference
      between C. gobio and the 450 nm Baikal group can be ascribed to the presence of a
      porphyropsin/rhodopin mixture in C. gobio. Subsequent analysis of amino acid
      substitutions by site-directed mutagenesis demonstrates that the remainder of the
      shift from 461 to 450 nm arises from a Thr269Ala substitution and the shift from
      450 to 430 nm at least partly from Thr118Ala and Thr118Gly substitutions. The
      underlying adaptive significance of these substitutions in terms of spectral
      tuning and signal-to-noise ratio is discussed.

PMID- 11993997
TI  - Vibrational frequency and dipolar orientation of the protonated Schiff base in
      bacteriorhodopsin before and after photoisomerization.
AB  - Light-driven proton transport in bacteriorhodopsin (BR) is initiated by
      photoisomerization of the retinylidene chromophore, which perturbs the hydrogen
      bonding network in the Schiff base region of the active site. This study aimed to
      identify the frequency and dipolar orientation of the N-D stretching vibrations
      of the Schiff base before and after photoisomerization, by means of low
      temperature polarized FTIR spectroscopy of [zeta-(15)N]lysine-labeled BR in
      D(2)O. (15)N-shifted modes were found at 2123 and 2173 cm(-1) for BR, and at 2468
      and 2495 cm(-1) for the K intermediate. The corresponding N-H stretches are at
      approximately 2800 cm(-1) for BR and 3350-3310 cm(-1) for the K intermediate. The
      shift to a 350 cm(-1) higher frequency upon photoisomerization is consistent with
      loss of the hydrogen bond of the Schiff base. The N-D stretch frequencies of the
      Schiff base in BR and the K intermediate are close to the O-D stretch frequencies
      of strongly hydrogen bonded water and Thr89, respectively. The angles of the
      dipole moments of the N-D stretches to the membrane normal were determined to be
      60-65 degrees for BR and approximately 90 degrees for the K intermediate. In the
      case of BR, the stretch orientation is expected to deviate from the N-D bond
      orientation due to vibrational mixing in the hydrogen bonding network. In
      contrast, the data for the K intermediate suggest that the N-D group is not
      hydrogen bonded and orients along the membrane.

PMID- 11993998
TI  - Stopped-flow studies of the kinetics of single-stranded DNA binding and wrapping
      around the Escherichia coli SSB tetramer.
AB  - We have examined the kinetic mechanism for binding of the homotetrameric
      Escherichia coliSSB protein to single-stranded oligodeoxynucleotides [(dT)(70)
      and (dT)(35)] under conditions that favor the formation of a fully wrapped ssDNA
      complex in which all four subunits interact with DNA. Under these conditions, a
      so-called (SSB)(65) complex is formed in which either one molecule of (dT)(70) or
      two molecules of (dT)(35) bind per tetramer. Stopped-flow studies monitoring
      quenching of the intrinsic SSB Trp fluorescence were used to examine the initial
      binding step. To examine the kinetics of ssDNA wrapping, we used a single
      stranded oligodeoxythymidylate, (dT)(66), that was labeled on its 3'-end with a
      fluorescent donor (Cy3) and on its 5'-end with a fluorescent acceptor (Cy5).
      Formation of the fully wrapped structure was accompanied by extensive
      fluorescence resonance energy transfer (FRET) from Cy3 to Cy5 since the two ends
      of (dT)(66) are in close proximity in the fully wrapped complex. Our results
      indicate that initial ssDNA binding to the tetramer is very rapid, with a
      bimolecular rate constant, k(1,app), of nearly 10(9) M(-1) s(-1) in the limit of
      low salt concentration (<0.2 M NaCl, pH 8.1, 25.0 degrees C), whereas the rate of
      dissociation is very low at all salt concentrations that were examined (20 mM to
      2 M NaCl or NaBr). However, the rate of initial binding and the rate of formation
      of the fully wrapped complex are identical, indicating that the rate of wrapping
      of the ssDNA around the SSB tetramer is very rapid, with a lower limit rate of
      700 s(-1). The implications of this rapid binding and wrapping reaction are
      discussed.

PMID- 11993999
TI  - Mutation of a single TMVI residue, Phe(282), in the beta(2)-adrenergic receptor
      results in structurally distinct activated receptor conformations.
AB  - We showed previously that Phe(303) in transmembrane segment (TM) VI of the
      alpha(1B)-adrenergic receptor (alpha(1B)-AR), a residue conserved in many G
      protein-coupled receptors (GPCRs), is critically involved in coupling agonist
      binding with TM helical movement and G protein activation. Here the equivalent
      residue, Phe(282), in the beta(2)-AR was evaluated by mutation to glycine,
      asparagine, alanine, or leucine. Except for F282N, which exhibits attenuated
      basal and maximal isoproterenol stimulation, the Phe(282) mutants display varying
      degrees of constitutive activity (F282L > F282A > F282G), and as shown by the
      results of substituted cysteine accessibility method (SCAM) studies, induce
      movement of endogenous cysteine(s) into the water-accessible ligand-binding
      pocket. For F282A, movement is confined to Cys(285) in TMVI, whereas F282L
      induces movement of both Cys(285) in TMVI and Cys(327) in TMVII. Further,
      engineered cysteine-sensor studies indicate that F282L causes movement of TMVI,
      both above and below an apparent kink-inducing TMVI proline (Pro(288)), whereas
      that due to F282A is confined to the domain below Pro(288). A plausible
      interpretation of these data is that receptor activation involves rigid body
      movement of TMVI which, because of its Pro(288)-induced kink, acts as a pivot to
      transduce and amplify the agonist-induced conformational change in the upper
      domain, to a change in the lower domain required for productive receptor-G
      protein coupling.

PMID- 11994000
TI  - Modulation of triple-helical stability and subsequent melanoma cellular responses
      by single-site substitution of fluoroproline derivatives.
AB  - Collagen is a multifunctional protein, serving as a structural scaffold and a
      modulator of cellular responses. Prior work has identified distinct regions from
      several collagen types that promote cell adhesion, spreading, migration, and
      signal transduction. One of these regions, alpha1(IV)1263-1277 from type IV
      collagen, mediates these responses via melanoma cell CD44-chondrotin sulfate
      proteoglycan receptors. In the study presented here, we have used a triple
      helical model of alpha1(IV)1263-1277 to evaluate (a) conformational stability and
      (b) cellular responses based on single-site incorporation of trans-4-fluoro-L
      proline (trans-Flp) or cis-4-fluoro-L-proline (cis-Flp) for trans-4-hydroxy-L
      proline (trans-Hyp). The structural effects of cis-Flp and trans-Flp substitution
      were studied by circular dichroism and NMR spectroscopies. The peptide containing
      a single trans-Flp instead of trans-Hyp was slightly more thermally stable than
      the parent peptide (T(m) = 37 vs 34 degrees C), while the peptide containing cis
      Flp was considerably less stable than the parent peptide (T(m) = 30 degrees C).
      Melanoma cell adhesion and spreading were examined under conditions where the
      trans-Hyp-, trans-Flp-, and cis-Flp-containing ligands were approximately 15,
      <10, and approximately 65% denatured, respectively. Adhesion to each of the three
      ligands was remarkably sensitive to the respective ligand conformation, with
      EC(50) values of approximately 2.5, approximately 0.35, and >5.0 microM for the
      trans-Hyp-, trans-Flp-, and cis-Flp-containing ligands, respectively. Melanoma
      cell spreading was quantitated over a ligand concentration range of 0.01-50
      microM and, in a fashion similar to adhesion, was more extensive on the trans-Flp
      ligand than on the trans-Hyp ligand. Very low levels of spreading were observed
      with the cis-Flp-containing ligand at all concentrations tested. Melanoma cell
      adhesion to and spreading on the three ligands suggested the dramatic biological
      consequence of even subtle changes in relative triple-helical content. Such
      subtle changes may model those occurring in the basement membrane during the
      tumor cell invasion process, and thus provide mechanistic insight into this stage
      of metastasis.

PMID- 11994001
TI  - Selective inhibition of the C-domain of angiotensin I converting enzyme by
      bradykinin potentiating peptides.
AB  - Somatic angiotensin I converting enzyme (ACE) contains two functional active
      sites. Up to now, most of the studies aimed at characterizing the selectivity of
      inhibitors toward the two ACE active sites relied on the use of ACE mutants
      containing a single functional active site. By developing new fluorogenic
      synthetic substrates of ACE, we demonstrated that inhibitor selectivity can be
      assessed directly by using somatic ACE. This useful screening approach led us to
      discover that some bradykinin potentiating peptides turned out to be selective
      inhibitors of the C-domain of ACE. The peptide pGlu-Gly-Leu-Pro-Pro-Arg-Pro-Lys
      Ile-Pro-Pro, with K(i)(app) values of 30 nM and 8 microM, respectively, for the C
      and N-domain of ACE, is to our knowledge the most highly selective C-domain
      inhibitor of ACE so far reported. Inhibitors able to block selectively either the
      N- or C-domain of ACE will represent unique tools to probe the function of each
      domain in the regulation of blood pressure or other physiopathological events
      involving ACE activity.

PMID- 11994002
TI  - Evidence for flexibility in the function of ribonuclease A.
AB  - The dynamic properties of the enzyme ribonuclease A (RNase A) were investigated
      through the use of solution NMR spin relaxation experiments. As determined by
      "model-free" analysis, RNase A is conformationally rigid on time scales faster
      than overall rotational tumbling (picoseconds to nanoseconds). The average order
      parameter, S(2), for RNase A is 0.910 +/- 0.051. However, 28 of the amino acid
      residues in RNase A were identified as undergoing chemical exchange on the
      microsecond to millisecond time scale. For 16 of these residues the microscopic
      chemical exchange rates, k(ex), were quantitated through the use of the
      relaxation-compensated CPMG (rcCPMG) experiment. The value of k(ex) was identical
      for all residues with an average of 1640 s(-1) and is similar to the RNase A
      k(cat) value of 1900 s(-1). Many of these mobile residues localize to the active
      site in RNase A and include the catalytically crucial amino acids His119 and
      Asp121. Additional motion is found in the B1, B2, and P0 subsites, suggesting a
      coupling of motion between the binding and catalytic sites. The activation energy
      of the observed millisecond motion was measured by applying the rcCPMG experiment
      at temperatures of 283, 293, and 298 K and was determined to vary between 3.6 and
      7.4 kcal/mol. The measured barrier to conformational motion is similar to the
      activation barrier for the RNase A catalyzed reaction and thus would not be
      thermodynamically limiting to catalysis. These studies suggest a correlation of
      conformational exchange kinetics and thermodynamics derived from NMR measurements
      with those determined by biochemical means and are suggestive of an important
      role for flexibility in enzyme function.

PMID- 11994003
TI  - Equilibrium studies on the association of the nuclear poly(A) binding protein
      with poly(A) of different lengths.
AB  - The nuclear poly(A) binding protein (PABPN1) binds the growing poly(A) tail
      during pre-mRNA 3'-end processing, stimulating its elongation and controlling its
      final length. Here we report binding studies of PABPN1 to poly(A) in solution.
      Quantitative fluorescence titration was used to determine the stoichiometry,
      intrinsic affinity, and cooperativity of binding to a series of size-fractionated
      poly(A). The intrinsic association constant K(i) was about 2 x 10(6) M(-1) for
      oligo(A) and all size classes of poly(A). The binding of PABPN1 to poly(A) was
      enhanced by protein-protein interactions which were, however, weak (cooperativity
      parameter omega < 50). No significant change of cooperativity could be detected
      with increasing polynucleotide length in the range of 140-450 nucleotides. An
      average binding site size n of 11-14 was found for all poly(A) lengths, which is
      close to the minimal site size m found for binding to oligo(A). The data are
      discussed with respect to the previous observation of two different forms of the
      poly(A)-PABPN1 complex.

PMID- 11994004
TI  - Translesion synthesis by human DNA polymerase eta across thymine glycol lesions.
AB  - The XP-V (xeroderma pigmentosum variant) gene product, human DNA polymerase eta
      (pol eta), catalyzes efficient and accurate translesion synthesis (TLS) past cis
      syn thymine-thymine dimers (TT dimer). In addition, recent reports suggest that
      pol eta is involved in TLS past various other types of lesion, including an
      oxidative DNA damage, 8-hydroxyguanine. Here, we compare the abilities of pol
      alpha and pol eta to replicate across thymine glycol (Tg) using purified
      synthetic oligomers containing a 5R- or 5S-Tg. DNA synthesis by pol alpha was
      inhibited at both steps of insertion of a nucleotide opposite the lesion and
      extension from the resulting product, indicating that pol alpha can weakly
      contribute to TLS past Tg lesions. In contrast, pol eta catalyzed insertion
      opposite the lesion as efficient as that opposite undamaged T, while extension
      was inhibited especially on the 5S-Tg template. Thus, pol eta catalyzed
      relatively efficient TLS past 5R-Tg than 5S-Tg. To compare the TLS abilities of
      pol eta for these lesions, we determined the kinetic parameters of pol eta for
      catalyzing TLS past a TT dimer, an N-2-acetylaminofluorene-modified guanine, and
      an abasic site analogue. The possible mechanisms of pol eta-catalyzed TLS are
      discussed on the basis of these results.

PMID- 11994005
TI  - Translesion synthesis by human DNA polymerase kappa on a DNA template containing
      a single stereoisomer of dG-(+)- or dG-(-)-anti-N(2)-BPDE (7,8-dihydroxy-anti
      9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene).
AB  - Several recently discovered human DNA polymerases are associated with translesion
      synthesis past DNA adducts. These include human DNA polymerase kappa (pol kappa),
      a homologue of Escherichia coli pol IV, which enhances the frequency of
      spontaneous mutation. Using a truncated form of pol kappa (pol kappa Delta C),
      translesion synthesis past dG-(+)- or dG-(-)-anti-N(2)-BPDE (7,8-dihydroxy-anti
      9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) adducts was explored. Site
      specifically-modified oligodeoxynucleotides containing a single stereoisomeric dG
      N(2)-BPDE lesion were used as DNA templates for primer extension reactions
      catalyzed by pol kappa Delta C. Primer extension was retarded one base prior to
      the dG-N(2)-BPDE lesion; when incubated for longer times or with higher
      concentration of enzyme, full primer extension was observed. Quantitative
      analysis of fully extended products showed preferential incorporation of dCMP,
      the correct base, opposite all four stereoisomeric dG-N(2)-BPDE lesions. (+)
      trans-dG-N(2)-BPDE, a major BPDE-DNA adduct, promoted small amounts of dTMP,
      dAMP, and dGMP misincorporation opposite the lesion (total 2.7% of the starting
      primers) and deletions (1.1%). Although (+)-cis-dG-N(2)-BPDE was most effective
      in blocking translesion synthesis, its miscoding properties were similar to other
      dG-N(2)-BPDE isomers. Steady-state kinetic data indicate that dCMP is efficiently
      inserted opposite all dG-N(2)-BPDE adducts and extended past these lesions. The
      relative frequency of translesion synthesis (F(ins) x F(ext)) of dC.dG-N(2)-BPDE
      pairs was 2-6 orders of magnitude higher than that of other mismatched pairs. Pol
      kappa may play an important role in translesion synthesis by incorporating
      preferentially the correct base opposite dG-N(2)-BPDE. Its relatively low
      contribution to mutagenicity suggests that other newly discovered DNA
      polymerase(s) may be involved in mutagenic events attributed to dG-N(2)-BPDE
      adducts in human cells.

PMID- 11994006
TI  - High-field EPR study of tyrosyl radicals in prostaglandin H(2) synthase-1.
AB  - Various tyrosyl radicals generated by reaction of both native and indomethacin
      inhibited ovine prostaglandin H synthase-1 with ethyl hydrogen peroxide were
      examined by using high-field/high-frequency EPR spectroscopy. The spectra for the
      initially formed tyrosyl radical commonly referred to as the "wide-doublet"
      species and the subsequent "wide-singlet" species as well as the indomethacin
      inhibited "narrow-singlet" species were recorded at several frequencies and
      analyzed. For all three species, the g-values were distributed. In the case of
      the wide doublet, the high-field EPR spectra indicated that dominant hyperfine
      coupling was likely to be also distributed. The g(x)-values for all three
      radicals were found to be consistent with a hydrogen-bonded tyrosyl radical. In
      the case of the wide-doublet species, this finding is consistent with the known
      position of the radical and the crystallographic structure and is in
      contradiction with recent ENDOR measurements. The high-field EPR observations are
      consistent with the model in which the tyrosyl phenyl ring rotates with respect
      to both the protein backbone and the putative hydrogen bond donor during
      evolution from the wide-doublet to the wide-singlet species. The high-field
      spectra also indicated that the g-values of two types of narrow-singlet species,
      self-inactivated and indomethacin-inhibited, were likely to be different, raising
      the possibility that the site of the radical is different or that the binding of
      the inhibitor perturbs the electrostatic environment of the radical. The 130 GHz
      pulsed EPR experiments performed on the wide-doublet species indicated that the
      possible interaction between the radical and the oxoferryl heme species was very
      weak.

PMID- 11994007
TI  - Growth of beta-amyloid(1-40) protofibrils by monomer elongation and lateral
      association. Characterization of distinct products by light scattering and atomic
      force microscopy.
AB  - Amyloid plaques in brain tissue are a hallmark of Alzheimer's disease. Primary
      components of these plaques are 40- and 42-residue peptides, denoted A beta(1-40)
      and A beta(1-42), that are derived by proteolysis of cellular amyloid precursor
      protein. Synthetic A beta(1-40) and A beta(1-42) form amyloid fibrils in vitro
      that share many features with the amyloid in plaques. Soluble intermediates in A
      beta fibrillogenesis, termed protofibrils, have been identified previously, and
      here we describe the in vitro formation and isolation of A beta(1-40)
      protofibrils by size exclusion chromatography. In some experiments, the A beta(1
      40) was radiomethylated to better quantify various A beta species. Mechanistic
      studies clarified two separate modes of protofibril growth, elongation by monomer
      deposition and protofibril-protofibril association, that could be resolved by
      varying the NaCl concentration. Small isolated protofibrils in dilute Tris-HCl
      buffers were directed along the elongation pathway by addition of A beta(1-40)
      monomer or along the association pathway by addition of NaCl. Multi-angle light
      scattering analysis revealed that protofibrils with initial molecular masses M(w)
      of (7-30) x 10(3) kDa grew to M(w) values of up to 250 x 10(3) kDa by these two
      growth processes. However, the mass per unit length of the associated
      protofibrils was about 2-3 times that of the elongated protofibrils. Rate
      constants for further elongation by monomer deposition with the elongated,
      associated, and initial protofibril pools were identical when equal number
      concentrations of original protofibrils were compared, indicating that the
      original number of protofibril ends had not been altered by the elongation or
      association processes. Atomic force microscopy revealed heterogeneous initial
      protofibrils that became more rodlike following the elongation reaction. Our data
      indicate that protofibril elongation in the absence of NaCl results from monomer
      deposition only at the ends of protofibrils and proceeds without an increase in
      protofibril diameter. In contrast, protofibril association occurs in the absence
      of monomer when NaCl is introduced, but this association involves lateral
      interactions that result in a relatively disordered fibril structure.

PMID- 11994008
TI  - Identification of a contact region between the tridecapeptide alpha-factor mating
      pheromone of Saccharomyces cerevisiae and its G protein-coupled receptor by
      photoaffinity labeling.
AB  - Saccharomyces cerevisiae haploid cells communicate with their opposite mating
      type through peptide pheromones (alpha-factor and a-factor) that activate G
      protein-coupled receptors (GPCRs). S. cerevisiaewas used as a model system for
      the study of peptide-responsive GPCRs. Here, we detail the synthesis and
      characterization of a number of alpha-factor (Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly
      Gln-Pro-Met-Tyr) pheromone analogues containing the photo-cross-linkable group 4
      benzoyl-L-phenylalanine (Bpa). Following characterization, one analogue, [Bpa(1),
      Tyr(3), Arg(7), Phe(13)]alpha-factor, was radioiodinated and used as a probe for
      Ste2p, the GPCR for alpha-factor. Binding of the di-iodinated probe was saturable
      (K(d) = 200 nM) and competable by alpha-factor. Cross-linking into Ste2p was
      specific for this receptor and reversed by the wild-type pheromone. Chemical and
      enzymatic cleavage of the receptor/radioprobe complex indicated that cross
      linking occurred on a portion of Ste2p spanning residues 251-294 which
      encompasses transmembrane domain 6, the extracellular loop between transmembrane
      domains 6 and 7, and transmembrane domain 7. This fragment was verified using T7
      epitope-tagged Ste2p and a biotinylated, photoactivatable alpha-factor. After
      cross-linking with the biotinylated photoprobe and trypsin cleavage, the cross
      linked receptor fragment was revealed by both an anti T7-epitope antibody and a
      biotin probe. This is the first determination of a specific contact region
      between a Class IV GPCR and its ligand. The results demonstrate that Bpa alpha
      factor probes are useful in determining contacts between alpha-factor and Ste2p
      and initiate mapping of the ligand binding site of this GPCR.

PMID- 11994009
TI  - Probing the topology of the glycine receptor by chemical modification coupled to
      mass spectrometry.
AB  - Tetranitromethane (TNM), a small aqueous reagent that specifically modifies
      solvent-accessible tyrosine residues to o-nitrotyrosine, was used to probe the
      topology of the GlyR. Homomers of human alpha1 GlyR were recombinantly expressed
      via a baculovirus system, affinity-purified, and reconstituted in lipid vesicles
      of defined composition. The native-like reconstituted receptors were then reacted
      with TNM, and GlyR reaction products were isolated by SDS-PAGE. After proteolytic
      digestion, TNM-labeled residues were identified using mass spectrometry by
      observing the mass shift corresponding to the nitrate moiety. In this manner, we
      have identified TNM modifications of tyrosine residues at positions 24, 75, 78,
      161, 223, and 228 in the receptor. Of significance, nitrations at Tyr 223 and Tyr
      228 occur within the first putative transmembrane helix (M1) of the receptor, and
      their labeling suggests a non-helical secondary structure for M1 for the glycine
      receptor. In a previously published report [Leite et al. (2000) J. Biol. Chem.
      275, 13683], we also identified proteolytic cleavage sites within M1. Taken
      together, these studies support a topological model where the "historical" M1
      segment cannot be entirely alpha-helical and may contain an extramembranous
      surface loop. Furthermore, we have also identified a tyrosine modification (Tyr
      161) within a region of the N-terminal domain critical in agonist and antagonist
      binding.

PMID- 11994010
TI  - Contribution of basic residues of the 70-80-loop to heparin binding and
      anticoagulant function of activated protein C.
AB  - The role of basic residues of the 70-80-loop, Arg(74), Arg(75), and Lys(78)
      (chymotrypsin numbering) in the catalytic function of activated protein C (APC)
      was investigated by expressing mutants of protein C in which these residues were
      replaced with Ala in three separate constructs. Following purification to
      homogeneity and activation by thrombin, the catalytic properties of the mutants
      were characterized with respect to their ability to cleave the chromogenic
      substrate Spectrozyme PCa, react with protein C inhibitor (PCI), and inactivate
      factor Va. Relative to wild-type APC, the mutants cleaved Spectrozyme PCa with
      identical or improved catalytic efficiencies. Similarly, PCI inhibited mutants
      with identical or improved second-order rate constants (k(2)) in the absence of
      heparin. However, the heparin-catalyzed inhibition of mutants by PCI was impaired
      approximately 10-fold. Analysis of k(2) values by a ternary complex model
      revealed that the affinities of mutants for heparin were impaired to a similar
      extent. Moreover, analysis of the NaCl gradient elution profiles of APC
      derivatives from Heparin-Sepharose supported this conclusion. An oligosaccharide
      containing 14 residues efficiently catalyzed the PCI inhibition of APC by a
      template mechanism. Further studies revealed that the ability of Arg(74) and
      Arg(75) mutants to inactivate factor Va was markedly impaired. We conclude that
      basic residues of the 70-80-loop are critical for the catalytic function of APC.

PMID- 11994011
TI  - Brain-specific metallothionein-3 has higher metal-binding capacity than
      ubiquitous metallothioneins and binds metals noncooperatively.
AB  - Zinc metabolism in the cells is largely regulated by ubiquitous small proteins,
      metallothioneins (MT). Metallothionein-3 is specifically expressed in the brain
      and is down regulated in Alzheimer's disease. We demonstrate by mass spectrometry
      that MT-3, in contrast to common MTs, binds Zn(2+) and Cd(2+) in a noncooperative
      manner and can also bind higher stoichiometries of metals than seven. MT-3
      reconstituted with seven metals exists in a dynamic equilibrium of different
      metalloforms, where the prevalent metalloform is Me(7)MT-3, but metalloforms with
      6, 8, and even 9 metals are also present. The results from pH and stability
      studies demonstrate that the heterogeneity of metalloforms originates from the N
      terminal beta-cluster, whereas the C-terminal alpha-cluster of MT-3 binds four
      metal ions such as that of common MTs. Experiments with EDTA demonstrate that the
      beta-cluster of ZnMT-3 has a higher metal transfer potential than the beta
      cluster of Zn(7)MT-2. Moreover, ZnMT-3 loses metals during ultrafiltration. MT-3,
      reconstituted with an excess of Zn(2+) or Cd(2+), exists as a dynamic mixture of
      metalloforms with higher than 7 metal stoichiometries (8-11). Such forms of ZnMT
      3 are unstable and decompose partly already during a rapid gel filtration,
      whereas CdMT-3 forms are more stable. Extra metal ions may bind to the beta
      cluster region as well as to the carboxylates of MT-3. The specific metal-binding
      properties of MT-3 could be functionally implemented for buffering of fluctuating
      concentrations of zinc in zincergic neurons and for transfer of zinc to synaptic
      vesicles.

PMID- 11994012
TI  - Yeast pyruvate decarboxylase tetramers can dissociate into dimers along two
      interfaces. Hybrids of low-activity D28A (or D28N) and E477Q variants, with
      substitution of adjacent active center acidic groups from different subunits,
      display restored activity.
AB  - The tetrameric enzyme yeast pyruvate decarboxylase (YPDC) has been known to
      dissociate into dimers at elevated pH values. However, the interface along which
      the dissociation occurs, as well as the fundamental kinetic properties of the
      resulting dimers, remains unknown. The active sites of YPDC are comprised of
      amino acid residues from two subunits, a property which we utilize to address the
      issue as to which dimer interface is cleaved under different conditions of
      dissociation. Hydroxide-induced dissociation of the active site D28A (or D28N)
      and E477Q variants, each at least 100 times less reactive than wild-type YPDC,
      followed by reassociation of D28A (or D28N) and E477Q variants led to a
      remarkable 35-50-fold increase in activity. This result is possible only if the
      hydroxide-induced dissociation results in a cleavage along the interface between
      two subunits so that residues D28 and E477 are now separated. Upon reassociation,
      one of the two active sites of the hybrid dimer will have both residues
      substituted, whereas the second one will be of the wild-type phenotype. In
      contrast to the hydroxide-induced dimers, the urea-induced dissociation recently
      proposed results in dissociation along dimer-dimer interfaces, without separating
      the active sites, and therefore, on reassociation, these dimers do not regain
      activity. The significance of the results is discussed in light of a recently
      proposed alternating sites mechanism for YPDC. A preparative ion-exchange method
      is reported for the separation and purification of hybrid enzymes.

PMID- 11994013
TI  - Ligand and oxidation-state specific regulation of the heme-based oxygen sensor
      FixL from Sinorhizobium meliloti.
AB  - Phosphorylation of the transcription factor RmFixJ is the key step in the hypoxic
      induction of Sinorhizobium meliloti nitrogen fixation genes. Oxygen regulates
      this process by binding reversibly to RmFixL, a heme protein kinase whose deoxy
      form catalyzes the phosphoryl transfer from ATP to RmFixJ. Here we present the
      first quantitative measure of the extent by which various heme ligands inhibit
      the turnover of RmFixJ to phospho-RmFixJ. We also quantitate the inhibition by
      ligands of the reaction of RmFixL with ATP, in the absence of RmFixJ, to form
      phospho-RmFixL, i.e., the "autophosphorylation". Phospho-RmFixL formed from
      autophosphorylation will transfer its phosphoryl group to RmFixJ in an oxygen
      independent "phosphotransfer." Here we show that the mode of substrate
      presentation, i.e., simultaneous versus sequential, influences the regulation of
      phosphoryl transfer by heme status. Inhibition factors for O(2), CO, NO, CN(-),
      and imidazole in the presence of RmFixJ are drastically different from the
      inhibition of autophosphorylation by the same ligands. Oxidation of the heme iron
      in unliganded RmFixL is known to have no effect on either of the sequential
      reactions; yet oxidation causes a 100-fold decrease in RmFixJ turnover when ATP
      and RmFixJ are presented simultaneously. The profound difference between the
      regulation of isolated RmFixL versus the complex of RmFixL with RmFixJ shows that
      interaction of a response regulator with its histidine-kinase partner need not be
      limited to the enzymatic regions of the histidine kinase, but can extend also to
      its sensory domain.

PMID- 11994014
TI  - Role of helix 3 in pore formation by the Bacillus thuringiensis insecticidal
      toxin Cry1Aa.
AB  - Helix 3 of the Cry1Aa toxin from Bacillus thuringiensis possesses eight charged
      amino acids. These residues, with the exception of those involved in
      intramolecular salt bridges (E90, R93, E112, and R115), were mutated individually
      either to a neutral or to an oppositely charged amino acid. The mutated genes
      were expressed, and the resultant, trypsin-activated toxins were assessed for
      their toxicity to Manduca sexta larvae and their ability to permeabilize M. sexta
      larval midgut brush border membrane vesicles to KCl, sucrose, raffinose,
      potassium gluconate, and N-methyl-D-glucamine hydrochloride with a light
      scattering assay based on osmotic swelling. Most mutants were considerably less
      toxic than Cry1Aa. Replacing either E101, E116, E118, or D120 by cysteine,
      glutamine, or lysine residues had only minor effects on the properties of the
      pores formed by the modified toxins. However, half of these mutants (E101C,
      E101Q, E101K, E116K, E118C, and D120K) had a significantly slower rate of pore
      formation than Cry1Aa. Mutations at R99 (R99C, R99E, and R99Y) resulted in an
      almost complete loss of pore-forming ability. These results are consistent with a
      model in which alpha-helix 3 plays an important role in the mechanism of pore
      formation without being directly involved in determining the properties of the
      pores.

PMID- 11994015
TI  - S-nitrosation of Ca(2+)-loaded and Ca(2+)-free recombinant calbindin D(28K) from
      human brain.
AB  - Calbindin D(28K) is noted for its abundance and specific distribution in
      mammalian brain and sensory neurons. It can bind three to five Ca(2+) ions and
      may act as a Ca(2+) buffer to maintain intracellular Ca(2+) homeostasis, but its
      exact role is still unknown. In the present study, mass spectrometric analysis
      reveals that the five cysteine residues in recombinant human brain calbindin
      D(28K) (rHCaBP) are derivatized with N-ethylmaleimide, consistent with the
      determination of 5.3 +/- 0.4 and 4.7 +/- 0.4 free thiols in the protein using the
      thiol-specific reagents 5,5'-dithiobis(2-nitrobenzoic acid) and 5-(octyldithio)-2
      nitrobenzoic acid, respectively. The results of UV-vis and circular dichroism
      absorption, intrinsic fluorescence, and mass spectrometry measurements indicate
      that both Ca(2+)-loaded (holo) and Ca(2+)-free (apo) rHCaBP are S-nitrosated by S
      nitrosocysteine (CysNO). The number of cysteine residues S-nitrosated in
      holorHCaBP and aporHCaBP are 2.6 +/- 0.05 and 3.4 +/- 0.09, respectively, as
      determined by the Saville assay. HolorHCaBP also undergoes S-nitrosation at one
      to three cysteine residues when exposed to S-nitrosoglutathione (GSNO), and
      Cys100 was found to be an S-nitrosation site by peptide mass mapping. Treatment
      of holorHCaBP with free NO resulted in a mass increase of 59 +/- 2 Da,
      corresponding to two NO adducts. Since up to four cysteine residues can be S
      nitrosated in rHCaBP, it is proposed that the protein may act as a NO buffer or
      reservoir in the brain in a manner similar to serum albumin in blood. It is
      significant in this context that rHCaBP is found coexistent with nitric oxide
      synthase in cerebellum and that S-nitrosation varies with Ca(2+) binding, with S
      nitrosation occurring to a greater extent in aporHCaBP than in the holoprotein.
      Furthermore, exposure of rHCaBP to either CysNO or GSNO also leads to rapid S
      thiolation of Cys187. We demonstrate here for the first time that intrinsic
      protein fluorescence is a sensitive probe of protein S-nitrosation. This is due
      to efficient Forster energy transfer (R(0) approximately 17 A) between tryptophan
      donors and S-nitrosothiol acceptors.

PMID- 11994016
TI  - Pyrococcus furiosus alpha-amylase is stabilized by calcium and zinc.
AB  - The hyperthermophilic archeon Pyrococcus furiosus produces an extracellular alpha
      amylase that belongs to glycosyl hydrolases' family 13. This enzyme is more
      thermostable than its bacterial and archaeal homologues (e.g., Bacillus
      licheniformis TAKA-term and Pyrococcus kodakaraensis KOD1 alpha-amylases,
      respectively) even without adding Ca(2+) ions. Unlike the TAKA-therm amylase that
      contains no cysteine, the P. furiosus enzyme contains five cysteines (C152, C153,
      C165, C387, and C430), only four of which (C152, C153, C387, and C430) are
      conserved in the P. kodakaraensis alpha-amylase. To test the potential function
      of cysteines in P. furiosus alpha-amylase stability, these five residues were
      substituted with Ser or Ala-either one-by-one or in sequence-to produce eight
      mutant enzymes. Mutation C165S dramatically destabilized P. furiosus alpha
      amylase. At the same time, the quadruple mutant enzyme C152S/C153S/C387S/C430A
      (mutant SSCSA) was as thermostable as the wild-type enzyme. Mutant SSCSA and wild
      type alpha-amylases were strongly destabilized by dithiothreitol and
      ethylenediaminetetraacetic acid, suggesting that metal binding can be involved in
      this enzyme's thermostability. Inductively coupled plasma-atomic emission
      spectrometry showed the presence of Ca(2+) and Zn(2+) metal ions in P. furiosus
      alpha-amylase. Although Ca(2+) is known to contribute to alpha-amylase's
      stability, the absence of two out of the three conserved Ca(2+) ligands in the P.
      furiosus enzyme suggests that a different set of amino acids is involved in this
      enzyme's Ca(2+) binding. We also provide evidence suggesting that Cys165 is
      involved in Zn(2+) binding and that Cys165 is essential for the stability of P.
      furiosus alpha-amylase at very high temperatures.

PMID- 11994017
TI  - Screening combinatorial libraries by mass spectrometry. 2. Identification of
      optimal substrates of protein tyrosine phosphatase SHP-1.
AB  - Protein tyrosine phosphatases (PTPs) are a large family of enzymes that catalyze
      the hydrolytic removal of the phosphoryl group from phosphotyrosyl (pY) proteins.
      In this work, we have developed a novel combinatorial library method, termed
      "enzyme-catalyzed loss of isotope peak signal enhancement (ECLIPSE)", to
      determine the substrate specificity of PTPs. This method involves partial
      labeling of pY at a nonbridging phosphate oxygen atom with 50% (18)O ((16)O/(18)O
      = 1:1). A 361-member solution-phase peptide library with randomization at the -1
      and -2 positions (relative to pY), RNNXXpYA-NH(2) (X = 19 alpha-amino acids
      except for Cys), was synthesized with the partially (18)O-labeled pY by the split
      synthesis method. Each member of the resulting pY peptide library appeared as a
      doublet peak in the mass spectrum (m/z m and m + 2.0043). Limited treatment of
      the library with a PTP removed the mass-degenerate phosphoryl group from the most
      preferred substrates to generate products as singlet peaks, which were readily
      identified and sequenced by tandem mass spectrometry. Screening of the pY library
      against the catalytic domain of SHP-1 revealed that SHP-1 prefers an acidic
      residue at the -2 position, with aspartic acid being slightly better than
      glutamic acid. At the -1 position, SHP-1 also prefers an acidic residue, although
      a variety of other amino acids are also tolerated. On the other hand, positively
      charged residues at these positions render the corresponding peptides very poor
      substrates of SHP-1. Several selected peptides were individually synthesized and
      assayed against SHP-1, and the kinetic data confirmed the screening results.
      These results demonstrate that ECLIPSE is a viable method for studying the
      substrate specificity of PTPs.

PMID- 11994018
TI  - Pros and cons for the development of new antiepileptic drugs.
AB  - There continues to be an escalation in the number of new antiepileptic drugs,
      with many recently marketed drugs and many more entering clinical trials. This
      growth begs the question as to whether we need additional antiepileptic drugs. We
      consider the answer to this question from the medical perspective and also from
      the viewpoint of the pharmaceutical industry, health providers and from a more
      global, international perspective. There is undoubtedly a medical need for new
      antiepileptic drugs, and despite growing competition, the antiepileptic drug
      market remains profitable. However, in health services with limited resources, it
      is important that this expense is not offset by failure to research more
      appropriate use of existing antiepileptic drugs that may have a greater impact on
      healthcare. This is especially true for developing countries where resources
      would be much better spent on prevention and closing the treatment gap (the
      difference between those who can be treated and those who are treated).

PMID- 11994019
TI  - Mood disorders in patients with epilepsy: epidemiology and management.
AB  - Patients with epilepsy are at high risk for depression because of an incompletely
      understood combination of factors that may be both psychosocial and neurological.
      Interictal depression in patients with epilepsy is an undertreated condition, in
      part because of concern regarding drug interactions and the risk of exacerbating
      seizures with antidepressant treatment. Bipolar disorder is not described as
      occurring with a higher than expected frequency in the population with epilepsy,
      but high rates of depression and suicide are well recognised, highlighting the
      need for more emphasis on antidepressive treatment in this group of at-risk
      patients. Neurological factors, including site and lateralisation of seizure
      focus, may be important for the development of depression, with left-sided
      seizure foci having a higher association with depressive symptoms. Forced
      normalisation may be a factor in the paradoxical onset of depression in patients
      with epilepsy whose seizures suddenly become well controlled by anti-seizure
      treatment. Lowering of folic acid levels by some antiepileptic drugs (AEDs) may
      also influence the expression of depression in patients with epilepsy. New AEDs
      continue to emerge as beneficial treatments themselves for mood disorders, with
      lamotrigine, gabapentin and, to a lesser extent, topiramate having clinical
      trials data to support their use in patients with bipolar disease. Similar
      positive data are available for vagal nerve stimulation. Mood effects of AEDs can
      be complicated, however, as many of these drugs (e.g. tiagabine) have also been
      reported to cause depression as an adverse effect. Electroconvulsive therapy in
      depressed patients with epilepsy requires special consideration. The selective
      serotonin reuptake inhibitors (SSRIs) and antidepressants that act at multiple
      receptors (e.g. nefazodone, venlafaxine) are the most appropriate treatments for
      depressed patients with epilepsy. Among these agents, citalopram has a low risk
      of interactions with AEDs. Bupropion, clomipramine and maprotiline are associated
      with a greater risk of seizures compared with other antidepressants and
      consequently should be used with caution in the treatment of depression in
      patients with epilepsy.

PMID- 11994020
TI  - CNS manifestations of cytomegalovirus infections: diagnosis and treatment.
AB  - Cytomegalovirus (CMV) infection of the CNS occurs most commonly in patients with
      severe immunosuppression such as those with advanced HIV infection (i.e. AIDS) or
      those who have undergone bone marrow or solid organ transplantation.
      Immunocompetent patients are affected very rarely. The infection of the CNS may
      affect the brain (diffuse encephalitis, ventriculoencephalitis, cerebral mass
      lesions) or the spinal cord (transverse myelitis, polyradiculomyelitis).
      Diagnosis is very difficult and should be based on clinical presentation, results
      of imaging and virological markers. The most specific diagnostic tool is the
      detection of CMV DNA by polymerase chain reaction in the CSF. Treatment should be
      initiated promptly if CMV infection is suspected. Antiviral therapy consists of
      intravenous ganciclovir, intravenous foscarnet or a combination of both.
      Cidofovir is the treatment of second choice. Patients who experience clinical
      improvement or stabilisation during induction therapy should be given maintenance
      therapy. After immune reconstitution (in HIV-positive patients) or
      discontinuation of immunosuppressive therapy (in transplant recipients),
      maintenance therapy may be stopped. Despite therapy, the prognosis for long-term
      survival is very poor, especially in patients with AIDS.

PMID- 11994021
TI  - Genetic predictors of therapeutic response to clozapine: current status of
      research.
AB  - Clozapine is one of the most clinically potent drugs currently available for
      treating the symptoms of schizophrenia. Compared with conventional antipsychotics
      it surpasses its predecessors in its ability to treat a wider range of symptoms
      in otherwise refractory patients, while possessing a low propensity to produce
      extrapyramidal symptoms. Despite its significant advantages, not all patients
      benefit from treatment. Some patients react adversely to therapy while others
      fail to respond adequately. If those most likely to benefit from clozapine could
      be identified prior to treatment, this would significantly improve the clinical
      management of these patients. Genetic alterations in drug-metabolising enzymes
      have previously been demonstrated to influence the efficacy of clinically
      relevant drugs. It is possible that similar alterations in these and other
      systems may influence the response variability of patients to clozapine.
      Pharmacogenetic studies are at present investigating genes encoding drug
      receptors, drug-metabolising enzymes and neurotransmitter transporters to
      identify genetic variants that may be important. To date polymorphisms within
      serotonergic and dopaminergic pathways have been implicated, though the
      involvement of similar variants in other candidate systems is also likely. This
      information will ultimately enable the genetic prediction of patients most likely
      to benefit from the drug, and in the process would alleviate the unnecessary
      exposure of predisposed individuals to potentially serious adverse effects.

PMID- 11994022
TI  - Brain metastases: treatment options to improve outcomes.
AB  - In recent years, a broader base of treatment options has evolved to improve the
      outcome for patients with brain metastases. The selection of the most appropriate
      intervention for the individual patient is dependent on a careful evaluation of
      the extent of intracranial tumour, as well as an understanding of patient and
      tumour characteristics that are important determinants of prognosis. Recent
      analyses have confirmed good performance status, control of the primary tumour,
      absence of extracranial metastases and age less than 65 years to be predictors
      for longer survival. Medical therapy typically includes the use of
      corticosteroids, and some advances have been made in optimising the use of these
      agents. Prophylactic use of antiepileptic drugs in patients with brain metastases
      is generally discouraged. Chemotherapy was previously not considered to have a
      role in treating brain metastases, but has increasingly become an accepted
      treatment option. Recent clinical studies have evaluated the integration of
      chemotherapy with conventional treatments such as radiotherapy and the addition
      of biological response modifiers. In the past, radiotherapy has been the mainstay
      of treatment for brain metastases. A number of randomised controlled trials have
      explored external beam radiation therapy, radiation sensitisers, postoperative
      whole brain irradiation and prophylactic cranial irradiation. Significant
      improvements in survival have been demonstrated as a result of prophylactic
      cranial irradiation in patients with small-cell lung cancer, and improved local
      control of brain metastases has been achieved with postoperative whole brain
      irradiation. A number of studies have helped define a more efficient use of
      external beam irradiation. Radiosurgery in particular has been identified as an
      important advance in radiation treatment delivery and may provide an acceptable
      alternative to surgical resection in many patients. Conventional surgery has long
      had a role to play in establishing the diagnosis, guiding the choice of
      subsequent therapies and reversing life-threatening complications from brain
      metastases. The risks of surgery have been reduced with recent improvements in
      anaesthesia and intraoperative tumour localisation. Recent clinical studies have
      addressed the role of surgical resection in the management of patients with a
      single brain metastasis. Survival benefits have been demonstrated in patients
      undergoing surgical resection in addition to external beam radiation therapy.
      Despite the improvements achieved in the treatment of patients with brain
      metastases at first diagnosis, the question of retreatment may arise in due
      course. The therapeutic options available in this situation include re-operation,
      radiosurgery and brachytherapy.

PMID- 11994024
TI  - Potential savings from splitting newer antidepressant medications.
AB  - BACKGROUND: The newer antidepressants are among the most commonly prescribed
      classes of medications. A favourable adverse effect profile and approvals for a
      wider range of disorders than their predecessors have fostered the growth of
      these drugs. However, newer antidepressants are appreciably more expensive than
      older medications, and the annual prescription costs of newer drugs are expected
      to continue to rise at double-digit rates. The price structuring of these
      medications is largely independent of their pill strengths, and splitting higher
      strength pills may reduce the average cost per dose by nearly half. Therefore,
      various health organisations and consumers have been using pill splitting to
      reduce prescription costs. Antidepressants are well suited for pill splitting
      because their therapeutic effects depend upon long-term alterations in
      neurotransmitters, and small variations in dose are not critical. OBJECTIVE: To
      examine the potential savings for various purchasers - health organisations and
      consumers - that can be derived from pill splitting of newer antidepressants.
      DESIGN AND SETTING: Product review and simulation study in the US healthcare
      setting. METHODS: All new antidepressants with pill strengths that could be
      halved and were not in capsular or time-release forms were included. Expenditures
      for purchasers of these pills were calculated using a variety of factors, such as
      the level of discounting of official average wholesale costs, average retail
      costs and the site of prescription dispensing. RESULTS: Seven antidepressants
      were included. In 2000, 42% of the pills of these antidepressants were at
      strengths that permitted splitting. If all eligible prescriptions had utilised
      split doses, purchasers could have saved over dollars US1.7 billion. The bulk of
      the saving (dollars US1.5 billion) would have been realised by pill splitting of
      only three medications - sertraline, paroxetine and citalopram. DISCUSSION AND
      CONCLUSIONS: The economic rationale for pill splitting of antidepressants is
      compelling for both health organisations and individual consumers. The literature
      indicates that when pill-splitters are used or a pharmacy cuts the pills,
      patients are satisfied and compliance is not reduced. However, pill splitting may
      be inadvisable for some subgroups of patients with reduced cognition or sensory
      or motor impairment, or older persons on polypharmacy. Pill splitting can be
      facilitated by mandating manufacturers to score all tablets, requiring
      pharmacists to fill prescriptions for split doses, and giving pharmacists
      incentives for splitting pills for patients. Finally, large-scale studies should
      be undertaken to examine the clinical effectiveness of, and financial savings
      from, pill splitting.

PMID- 11994023
TI  - The role of iron and copper in the aetiology of neurodegenerative disorders:
      therapeutic implications.
AB  - Abnormalities in the metabolism of the transition metals iron and copper have
      been demonstrated to play a crucial role in the pathogenesis of various
      neurodegenerative diseases. Metal homeostasis as it pertains to alterations in
      brain function in neurodegenerative diseases is reviewed in this article in
      depth. While there is documented evidence for alterations in the homeostasis,
      redox-activity and localisation of transition metals, it is also important to
      realise that alterations in specific copper- and iron-containing metalloenzymes
      appear to play a crucial role in the neurodegenerative process. These changes
      provide the opportunity to identify pathways where modification of the disease
      process can occur, potentially offering opportunities for clinical intervention.
      As understanding of disease aetiology evolves, so do the tools with which
      diseases are treated. In this article, we examine not only the possible mechanism
      of disease but also how pharmaceuticals may intervene, from direct and indirect
      antioxidant therapy to strategies involving gene therapy.

PMID- 11994025
TI  - Splitting antidepressant medications: more studies are needed to confirm clinical
      outcomes and potential savings.

PMID- 11994026
TI  - Is aspirin a cause of Reye's syndrome? A case against.
AB  - Reye's syndrome was a rare disease which appeared suddenly in the early 1950s and
      disappeared just as suddenly in the late 1980s. An association between Reye's
      syndrome and the ingestion of aspirin (acetylsalicylic acid) was claimed,
      although no proof of causation was ever established. The presence of salicylates
      in the blood or urine of Reye's syndrome patients has not been demonstrated, and
      no animal model of Reye's syndrome has been developed where aspirin causes the
      disease. It is clear from epidemiological data that the incidence of Reye's
      syndrome was decreasing well before warning labels were placed on aspirin
      products. Reye's syndrome disappeared from countries where aspirin was not used
      in children as well as from countries which continued to use aspirin in children.
      Reye's syndrome was probably either a viral mutation which spontaneously
      disappeared, or a conglomeration of metabolic disorders that had not been
      recognized or described at that time.

PMID- 11994028
TI  - A systematic review of the safety of kava extract in the treatment of anxiety.
AB  - This paper systematically reviews the clinical evidence relating to the safety of
      extracts of the herbal anxiolytic kava (Piper methysticum). Literature searches
      were conducted in four electronic databases and the reference lists of all papers
      located were checked for further relevant publications. Information was also
      sought from the spontaneous reporting schemes of the WHO and national drug safety
      bodies and ten manufacturers of kava preparations were contacted. Data from short
      term post-marketing surveillance studies and clinical trials suggest that adverse
      events are, in general, rare, mild and reversible. However, published case
      reports indicate that serious adverse events are possible including
      dermatological reactions, neurological complications and, of greatest concern,
      liver damage. Spontaneous reporting schemes also suggest that the most common
      adverse events are mild, but that serious ones occur. Controlled trials suggest
      that kava extracts do not impair cognitive performance and vigilance or
      potentiate the effects of central nervous system depressants. However, a possible
      interaction with benzodiazepines has been reported. It is concluded that when
      taken as a short-term monotherapy at recommended doses, kava extracts appear to
      be well tolerated by most users. Serious adverse events have been reported and
      further research is required to determine the nature and frequency of such
      events.

PMID- 11994027
TI  - Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used agents that despite
      chemically heterogeneity, share similar therapeutic properties and adverse
      effects. Topical ophthalmic NSAIDs are limited to the relatively water soluble
      phenylacetic and phenylalkanoic acids as well as indole derivatives, which are
      more suitable for ophthalmic use. Topical ophthalmic NSAIDs are commonly used in
      the treatment of post-operative inflammation following cataract extraction and
      various surgical refractive procedures. They are also used in the prevention and
      treatment of cystoid macular oedema and for the treatment of allergic
      conjunctivitis. Absorption of topical ophthalmic NSAIDs through the nasal mucosa
      results in systemic exposure and the occurrence of adverse systemic events,
      including exacerbation of bronchial asthma. Local irritant effects of topical
      ophthalmic NSAIDs include conjunctival hyperaemia, burning, stinging and corneal
      anaesthesia. A more serious complication involves the association of topical
      ophthalmic NSAIDs with indolent corneal ulceration and full-thickness corneal
      melts. Analysis of NSAID-associated corneal events implicates the now defunct
      generic dicolfenac product, diclofenac sodium ophthalmic solution as the agent
      primarily responsible. However, these events generated a renewed interest in the
      safety of ophthalmic NSAIDs and a scrutiny of the pharmacology regarding NSAID
      action in the eye. An elucidation of possible pharmacodynamic explanations of
      NSAID-induced corneal injury includes the role of epithelial hypoxia, which not
      only appears to aid in determining the metabolic destination of arachidonate, it
      may play a key role in orchestrating a novel inflammatory response unrelated to
      prostanoid formation. The use of NSAIDs under conditions of corneal hypoxia may
      therefore not only result in a disappointing therapeutic response, it may result
      in a paradoxical inflammatory exacerbation. Other potential mechanisms include
      the relationship between NSAIDs and corneal matrix metalloproteinase and direct
      toxicity due to cytotoxic excipients such as surfactants, solubilisers and
      preservatives found in topical NSAID ophthalmic preparations. In general,
      ophthalmic NSAIDs may be used safely with other ophthalmic pharmaceuticals;
      however, concurrent use of agents known to adversely effect the corneal
      epithelium, such as gentamicin, may lead to increased corneal penetration of the
      NSAID. The concurrent use of NSAIDs with topical corticosteorids in the face of
      significant pre-existing corneal inflammation has been identified as a risk
      factor in precipitating corneal erosions and melts and should be undertaken with
      caution. Until clinical evidence dictates otherwise, data supporting theories of
      potential pharmacodynamic mechanisms of NSAID injury do not alter the favorable
      benefit-risk ratio of ophthalmic NSAID use when employed in an appropriate and
      judicious manner.

PMID- 11994030
TI  - Determinants of headache in lansoprazole users in The Netherlands: results from a
      nested case-control study.
AB  - OBJECTIVE: During proton pump inhibitor (PPI) use, in clinical trials, headache
      is one of the most frequently reported adverse events (frequency 1.3 to 8.8%),
      while results of one observational study indicate that headache is the fifth most
      frequently reported adverse event (incidence densities 2.5 to 4.6 per 1000
      patient-months of exposure). However, there are no observational studies
      performed regarding the occurrence and features of headache during use of PPIs in
      daily practice. For this reason this study was set up with the aim to assess the
      incidence and characteristics of headache and to investigate possible associated
      co-factors in PPI users in daily practice. DESIGN: Data were used from a
      prospective, observational study in which 10 008 lansoprazole users were followed
      over time. The study was designed according to the Safety Assessment of Marketed
      Medicines guidelines. A nested case-control design was used to compare PPI users
      reporting headache or not. RESULTS: The frequency of headache was 2.5% in users
      of lansoprazole and the incidence density was 7.2 per 1000 patient-months of PPI
      lansoprazole use. Two-thirds of patients with headache had tension headache and
      one-third had migraine. The analysis of co-factors revealed that women, patients
      with previous use of analgesics and patients reporting several adverse events,
      were at risk to develop headache during PPI use. Patients with headache also,
      significantly more often, reported diarrhoea, nausea and dizziness. A
      discontinuation of PPI therapy resulted in a cessation or reduction of the
      headache in 80.0% (20 of 25). CONCLUSIONS: As can be expected, headache was
      reported less frequently in this study compared with clinical trials with
      lansoprazole. The incidence density was comparable with other observational data
      of lansoprazole and omeprazole users. Besides several commonly accepted co
      factors such as female gender and a history of analgesic use, we also found the
      reporting of other adverse events to be associated with the reporting of headache
      during lansoprazole use. The cessation of headache after a discontinuation of use
      of the PPI and the observed dose relationship suggested that headache was indeed
      an adverse effect of lansoprazole use.

PMID- 11994031
TI  - Should celecoxib be contraindicated in patients who are allergic to sulfonamides?

PMID- 11994029
TI  - Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade
      de pointes: an overview.
AB  - The long and growing list of non-antiarrhythmic drugs associated with
      prolongation of the QT interval of the electrocardiogram has generated concern
      not only for regulatory interventions leading to drug withdrawal, but also for
      the unjustified view that QT prolongation is usually an intrinsic effect of a
      whole therapeutic class [e.g. histamine H(1) receptor antagonists
      (antihistamines)], whereas, in many cases, it is displayed only by some compounds
      within a given class of non-antiarrhythmic drugs because of an effect on cardiac
      repolarisation. We provide an overview of the different classes of non
      antiarrhythmic drugs reported to prolong the QT interval (e.g. antihistamines,
      antipsychotics, antidepressants and macrolides) and discusses the clinical
      relevance of the QT prolonging effect. Drug-induced torsade de pointes are
      sometimes considered idiosyncratic, totally unpredictable adverse drug reactions,
      whereas a number of risk factors for their occurrence is now recognised.
      Widespread knowledge of these risk factors and implementation of a comprehensive
      list of QT prolonging drugs becomes an important issue. Risk factors include
      congenital long QT syndrome, clinically significant bradycardia or heart disease,
      electrolyte imbalance (especially hypokalaemia, hypomagnesaemia, hypocalcaemia),
      impaired hepatic/renal function, concomitant treatment with other drugs with
      known potential for pharmacokinetic/pharmacodynamic interactions (e.g. azole
      antifungals, macrolide antibacterials and class I or III antiarrhythmic agents).
      This review provides insight into the strategies that should be followed during a
      drug development program when a drug is suspected to affect the QT interval. The
      factors limiting the predictive value of preclinical and clinical studies are
      also outlined. The sensitivity of preclinical tests (i.e. their ability to label
      as positive those drugs with a real risk of inducing QT pronglation in humans) is
      sufficiently good, but their specificity (i.e. their ability to label as negative
      those drugs carrying no risk) is not well established. Verapamil is a notable
      example of a false positive: it blocks human ether-a-go-go-related (HERG) K(+)
      channels, but is reported to have little potential to trigger torsade de pointes.
      Although inhibition of HERG K(+) channels has been proposed as a primary test for
      screening purposes, it is important to remember that several ion currents are
      involved in the generation of the cardiac potential and that metabolites must be
      specifically tested in this in vitro test. At the present state of knowledge, no
      preclinical model has an absolute predictive value or can be considered as a gold
      standard. Therefore, the use of several models facilitates decision making and is
      recommended by most experts in the field.

PMID- 11994034
TI  - Genital herpes simplex virus infection in the adolescent: special considerations
      for management.
AB  - Genital herpes simplex virus (HSV) infections are increasingly common among
      adolescents. In developed countries, during the 1990s, adolescent HSV type 2
      seroprevalence rates ranged from 4 to 30% depending on the population studied.
      The clinical diagnosis of genital herpes may be unreliable and laboratory testing
      is recommended. Aciclovir, valaciclovir, and famciclovir are three antiviral
      drugs that have proven efficacy in the treatment of genital herpes. These drugs
      can be used in the treatment of the first episode or for recurrent infections, or
      can be used long term to suppress recurrent infections. Once or twice daily
      administration regimens are preferable for adolescents for reasons of adherence,
      and because it avoids the need to take medication at school. Unproven remedies
      are used commonly and can be harmful. In addition to antiviral therapy, proper
      management of the adolescent with genital herpes should also include
      developmentally appropriate explanations of the diagnosis, treatment and
      potential complications, recommendations for symptomatic relief, screening for
      other sexually transmitted infections, and discussion of safer sexual practices.
      All adolescents should have follow-up visits to complete education and counseling
      and to assess compliance with antiviral therapy.

PMID- 11994033
TI  - Current management strategies for the prevention and treatment of cytomegalovirus
      infection in pediatric transplant recipients.
AB  - Cytomegalovirus (CMV) is a significant cause of morbidity and mortality following
      transplantation, especially in the pediatric population, who remain at high risk
      of primary infection. The availability of effective antiviral therapy has led to
      dramatic improvements in the outcome of CMV infection in patients undergoing
      transplantation. In recent years, three major strategies have been developed for
      the prevention of CMV disease in this population: reduction of risk of viral
      acquisition or reactivation by management of risk factors; prophylaxis of all 'at
      risk' patients using prophylactic strategies for a defined period of time,
      initiated at or near the time of transplant; and pre-emptive treatment with
      ganciclovir of selected 'at-risk' patients, guided by either laboratory markers
      indicative of subclinical infection or the presence of specific risk factors. In
      general, well designed comparative studies of one or more antiviral agents for
      the prevention of CMV have not been carried out. While ganciclovir appears to be
      more effective than aciclovir, its tolerability profile is less optimal. The use
      of foscarnet avoids myelosuppresions, but is associated with significant
      nephrotoxicity. Its use should be reserved for patients unable to tolerate
      ganciclovir or with ganciclovir-resistant CMV disease. Similar to foscarnet, the
      high frequency of nephrotoxicity associated with the use of cidofovir limits its
      use to clinical scenarios suggestive of ganciclovir resistance. Newer options,
      such as valaciclovir and valganciclovir, are currently under investigation and
      preliminary experience has been promising. Finally, passive immunoprophylaxis has
      been shown to prevent CMV disease after solid organ transplantation, but its use
      in bone marrow transplantation is controversial. Essentially, pre-emptive
      strategies have relied on the quantitation in the peripheral blood of CMV
      phosphoprotein pp65 antigen and/or the polymerase chain reaction assay. Strict
      guidelines for the use of those assays as a guide to pre-emptive therapy have not
      been standardized. Prospective trials comparing pre-emptive therapy using either
      intravenous or oral ganciclovir, and now oral valganciclovir or valaciclovir, are
      necessary to determine the relative cost effectiveness and efficacy of these
      alternative strategies. Finally, it remains controversial as to whether
      prophylaxis or pre-emptive therapy is the optimal strategy for preventing CMV
      disease. While a growing body of literature describes these approaches in adult
      transplant recipients, published experience in children has been much more
      limited.

PMID- 11994036
TI  - Juvenile dermatomyositis: recognition and treatment.
AB  - Juvenile dermatomyositis (JDM) is a multisystem disease characterized by acute
      and chronic lymphocytic inflammation of the skeletal muscle and skin. The disease
      is marked early in its course by the presence of a vasculopathy or vasculitis,
      and later by the development of calcinosis. Research has focused on the
      epidemiology, etiology, and pathogenesis of the disease with, until more
      recently, limited therapeutic interventions. This article highlights treatment
      regimens, both traditional and more recent interventions. Traditional treatment
      for JDM includes high dose corticosteroid treatment with additional agents used
      in resistant disease or children with unwarranted adverse effects. Traditional
      therapy begins with daily oral corticosteroids, with intravenous corticosteroids
      utilized in severe disease; however, recent data suggests that short-term use of
      intravenous corticosteroids will allow a short-term improvement in strength, with
      no long-term change in outcome. More recent investigations suggest that early
      intervention with additional immunomodulatory agents will allow for a faster
      recovery, with less medication and disease sequelae. Use of methotrexate as an
      agent early in the disease course is becoming common place. Methotrexate, in
      conjunction with oral corticosteroids, allows a rapid improvement in symptoms,
      and allows for a more rapid reduction in corticosteroid dose. Methotrexate is
      considered as a steroid sparing agent, whether oral or intravenous
      corticosteroids are used. Additional immunomodulatory agents include the use of
      cyclosporine with or without methotrexate. Intravenous immunoglobulin has been
      reported to have benefit in resistant disease. There are exciting new agents
      which have great potential in treating JDM. Many of these agents are termed
      biologics and are being tested in adult myositis and juvenile arthritis. These
      include tumor necrosis factor (TNF)-alpha inhibitors, such as a chimeric
      monoclonal antibody to TNF-alpha, and a recombinant soluble human TNF receptor
      (p75)-Fc fusion protein. Many other new biological agents are also being tested
      in myositis.

PMID- 11994035
TI  - Which strategy for pertussis vaccination today?
AB  - Pertussis (whooping cough) remains an epidemic disease responsible for infant and
      child morbidity and mortality, and is perceived as a serious public health
      problem. Since the widespread use of whole-cell pertussis vaccines in the 1940s,
      vaccination programs have varied greatly between countries. National specificity
      is a function of several factors. The most important are: vaccine efficacy and
      tolerability;vaccine coverage and distribution; and vaccine acceptance by parents
      and professionals. During the 1970s, Sweden, England, Wales and Japan provided
      contrasting examples of the attitude of health authorities to the use of whole
      cell vaccines. The increase in pertussis incidence was noted as a consequence of
      active opposition to this vaccine. The re-emergence of pertussis in the 1990s, in
      countries with high vaccination coverage and increased incidence of disease in
      individuals >15 years and <6 months of age, has drawn attention to the role of
      booster doses of pertussis vaccines and their introduction into regular
      vaccination programs. The use of acellular vaccines for booster doses for
      adolescents and adults would seem unambiguous because of their decreased
      reactogenicity, although the exact schedule has yet to be established. The choice
      between the two kinds of vaccines is more difficult for primary courses, where
      safety and efficacy profiles are similar, and the attitude towards acellular
      vaccines varies from country to country. In this case, the strategy adopted
      results from the national history of pertussis infection and from the quality of
      the available whole-cell vaccine. Two contrasting examples are the US, where
      acellular vaccines were licensed for the primary series in the 1990s, and the UK,
      where whole-cell vaccines are exclusively used for primary immunization. The
      changing epidemiology of pertussis, and its local diversification, would suggest
      that at present it is difficult to define a single worldwide strategy with only
      one kind of vaccine and one schedule. In order to control pertussis incidence,
      each country should continue to determine the best national vaccination program
      established in very close relation to the past and present epidemiological
      situation and available healthcare resources.

PMID- 11994037
TI  - Formulations of antibiotics for children in primary care: effects on compliance
      and efficacy.
AB  - This review article is designed for pediatricians as well as primary care
      physicians in the outpatient setting as a clinical guide to antibiotic selection.
      It emphasizes variables related to compliance as well as efficacy. The aim is to
      give recommendations as to the choice of antibiotics, depending on factors such
      as taste, cost, efficacy, and compliance. Common bacterial pathogens causing
      infections in children are reviewed, along with their susceptibility patterns to
      antimicrobial agents. Emerging mechanisms of resistance, particularly the
      increasing resistance of pneumococci to beta-lactam antibiotics, are discussed
      because of their importance to antibiotic selection. Previously published studies
      that have examined the treatment of common outpatient infections in children,
      such as otitis media, streptococcal tonsillopharyngitis, and sinusitis, are
      summarized. Adverse reactions associated with antibiotics, second in importance
      only to efficacy, are reviewed. Finally, compliance issues, which include
      palatability, cost, duration of therapy, and administration frequency, are
      analyzed using recently published information related to each of these issues.
      The efficacy of the commonly used antibiotics for urinary tract infections,
      pneumonia, and streptococcal pharyngitis does not vary significantly; however,
      for otitis media and sinusitis, some studies have shown that treatment efficacy
      with the antibiotic does not vary significantly from that with placebo. Likewise,
      adverse reactions rarely provide a basis for antibiotic selection, since
      virtually all antibiotics are generally well tolerated. The final factor,
      compliance, is a major issue in determining both first- and second-line therapy
      of common outpatient infections in children. Although cost is not a factor in
      compliance in countries such as the UK where no copayment is required for
      pediatric drugs, it is of major importance in the US. This is followed by
      palatability, administration duration and finally administration frequency. As a
      group, cephalosporins are generally the best tasting but are relatively more
      expensive than macrolides. Antibiotics that can be given for 5 days, and just
      once or twice daily, are preferred by most parents and physicians. Since final
      assessment of antibiotic choice is likely to vary considerably among healthcare
      personnel, decisions must be made on an individual basis.

PMID- 11994038
TI  - Juvenile rheumatoid arthritis: therapeutic perspectives.
AB  - Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic
      autoimmune inflammatory disease. The therapeutic approach to JRA has, to date,
      been casual and based on extensions of clinical experiences gained in the
      management of adult rheumatoid arthritis (RA). The physiology of inflammation has
      been systemically studied and this has led to the identification of specific
      therapeutic targets and the development of novel approaches to the management of
      JRA. The classical treatments of the disease such as methotrexate, sodium
      aurothiomalate and sulfasalazine, are not always effective in controlling RA and
      JRA. This has necessitated the development of novel agents for treating RA, most
      of which are biological in nature and are targeted at specific sites of the
      inflammatory cascades. These biological therapeutic strategies in RA have proved
      successful and are being applied in the management of JRA. These developments
      have been facilitated by the advances in molecular biology which have heralded
      the advent of biodrugs (recombinant proteins) and gene therapy, in which specific
      genes can be introduced locally to enhance in vivo gene expression or suppress
      gene(s) of interest with a view to down-regulating inflammation. Some of these
      biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal
      antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept)
      and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be
      effective in RA. Etanercept has now been licensed for JRA. Clinical trials of
      infliximab in JRA are planned. Studies show that the clinical effects are
      transient, necessitating repeated treatments and the risk of vaccination effects.
      Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta
      and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these
      agents have to be administered parenterally and production costs are very high;
      thus, there is a need, especially for pediatric use, to develop agents that can
      be taken orally. Long-term studies will be required to assess the tolerability
      and toxicity of these approaches in JRA, since cytokines and other mediators play
      important roles in host defenses, and the chronic inhibition, exogenous
      administration or constitutive over-expression of some cytokines/mediators may
      have undesirable effects.

PMID- 11994039
TI  - Quality-of-life assessment in osteoporosis: health-status and preference-based
      measures.
AB  - Health-status and preference-based approaches to assessing health-related quality
      of life (HR-QOL) in osteoporosis are reviewed. Osteoporosis-targeted health
      status instruments [i.e. Osteoporosis Quality-of-Life Questionnaire (OQLQ),
      Osteoporosis Assessment Questionnaire (OPAQ), Quality-of-Life Questionnaire of
      the European Foundation for Osteoporosis (QUALEFFO), Osteoporosis-Targeted
      Quality-of-Life Questionnaire (OPTQoL), Osteoporosis Functional Disability
      Questionnaire (OFDQ), Quality-of-Life Questionnaire in Osteoporosis (QUALIOST)],
      which have been utilised to document the adverse impact of osteoporosis on HR-QOL
      in diverse clinical and epidemiological studies, are described first. Preference
      based approaches to osteoporosis health-outcome measurement are then considered
      in both clinical and health policy settings. In the clinical setting, direct
      preference assessments [i.e. visual analogue scale (VAS), time tradeoff (TTO),
      standard gamble (SG)] using either experienced or described health outcomes have
      consistently shown significantly lower values for osteoporosis-related health
      states relative to usual or ideal health. In the health-policy context,
      preference-classification systems [i.e. EuroQoL (EQ-5D), Health Utilities Index
      (HUI)] for valuing health in economic studies are reviewed. At present, there is
      little evidence to guide the choice of one system over another for assessing the
      cost effectiveness of osteoporosis interventions; however, use of a consistent
      set of health-state values is essential. Further research is needed to
      characterise associations between osteoporosis-targeted health-status instruments
      and preference-based health-outcome measures. In addition, the longitudinal
      impact of osteoporosis and related fractures on HR-QOL must be documented.

PMID- 11994040
TI  - Economic considerations related to providing adequate pain relief for women in
      labour: comparison of epidural and intravenous analgesia.
AB  - Epidural analgesia and intravenous analgesia with opioids are two techniques for
      providing pain relief for women in labour. Labour pain is comparable to surgical
      pain in its severity, and epidural analgesia provides better relief from this
      pain than intravenous analgesia; a meta-analysis quantified this improvement to
      be 40 mm on a 100mm pain scale during the first stage of labour. Epidural
      analgesia also has fewer adverse effects. However, providing epidural analgesia
      for labour pain costs more. The full cost of providing epidural analgesia can be
      divided into two components: a baseline-cost component, which captures the costs
      of hospital care to parturients receiving intravenous analgesia for labour pain;
      and an incremental-cost component, which estimates the costs arising from
      incremental care specific to epidural analgesia. The baseline component may be
      constructed using hospital cost-accounting data pertaining to actual obstetric
      patients. The incremental component is constructed from a set of recognised
      complications of epidural and intravenous analgesia, associated incidence rates
      and estimates of the costs involved, from society's perspective. The incremental
      expected cost per patient to society of providing epidural analgesia was
      calculated to be approximately $US338 (1998 values). This cost difference results
      primarily from increased professional costs (and is particularly sensitive to the
      method used to estimate the cost of anaesthesia professional services) and
      increased complication costs associated with epidural analgesia. A rational
      social policy for providing labour analgesia must weigh the value of improved
      pain relief from epidural analgesia against the increased cost of epidural
      analgesia.

PMID- 11994041
TI  - Cost effectiveness of oral terbinafine (Lamisil) compared with oral fluconazole
      (Diflucan) in the treatment of patients with toenail onychomycosis.
AB  - OBJECTIVE: To determine the cost effectiveness of terbinafine (Lamisil) tablets
      compared with fluconazole (Diflucan) capsules in the treatment of patients with
      toenail onychomycosis. METHODS: Data from a randomised, double-blind, double
      dummy, multicentre study were used as the basis for this study. Terbinafine 250
      mg/day for 12 weeks (n = 48) was compared with fluconazole 150mg once weekly for
      12 weeks (n = 45) or 24 weeks (n = 44) in patients with culture-confirmed toenail
      onychomycosis caused by dermatophyte infection. At the end of the study (week
      60), complete clinical cure of the target toenail was achieved in 67% of patients
      in the terbinafine group, compared with 21 and 32%, respectively, in the 12- and
      24-week fluconazole groups. We subsequently used these data to calculate the cost
      effectiveness of the three treatment regimens, defining cost effectiveness as the
      cost per complete clinical cure of the target toenail at week 60. RESULTS: The
      cost effectiveness of terbinafine for each complete clinical cure was superior to
      that of either of the fluconazole regimens. Costs per cure were Finnish markka
      (Fmk) 2824 ($US618) for terbinafine, compared with Fmk3748 ($US820) and Fmk4922
      ($US1077), respectively, for the two fluconazole regimens. CONCLUSIONS: The
      clinical study showed that terbinafine was significantly more effective than
      fluconazole in the treatment of onychomycosis, achieving statistically higher
      rates of mycological and clinical cure. We have now shown that terbinafine is
      also more cost effective. These findings have important implications for both
      medical and social policy.

PMID- 11994042
TI  - Economic evaluation of gemcitabine alone and in combination with cisplatin in the
      treatment of nonsmall cell lung cancer.
AB  - OBJECTIVE: To evaluate the cost effectiveness of gemcitabine in the treatment of
      nonsmall cell lung cancer (NSCLC). METHODS: Gemcitabine was compared with best
      supportive care and gemcitabine/cisplatin was compared with three standard
      chemotherapies and four other novel chemotherapy combinations. Costs and
      effectiveness measures were based on resource and outcome data from previously
      reported clinical trials. All direct costs associated with NSCLC treatment were
      included and adjusted to year 2000 values. PERSPECTIVE: UK National Health
      Service. RESULTS: Gemcitabine plus best supportive care was associated with an
      incremental cost per progression-free life year gained of pound sterling5228
      compared with best supportive care alone. In comparison with standard
      chemotherapies, gemcitabine/cisplatin was associated with an incremental cost per
      progression-free life year gained of pound sterling1751 versus
      etoposide/cisplatin and cost per 1-year survival gain of pound sterling5681
      versus mitomycin/vinblastine/platinum. Incremental cost per tumour response was
      pound sterling2032 relative to etoposide/cisplatin, pound sterling5169 relative
      to mitomycin/ifosfamide/cisplatin and pound sterling6240 relative to
      mitomycin/vinblastine/platinum. Compared with four novel (newer) combination
      chemotherapies gemcitabine/ cisplatin showed cost savings in each case, with the
      same or better outcome. Thus, gemcitabine/cisplatin showed improved cost
      effectiveness and dominance. Sensitivity analyses showed the results were robust
      to variations to the values of key parameters. CONCLUSION: Gemcitabine alone or
      in combination with cisplatin was assessed to be a cost-effective or cost-saving
      therapy when compared with best supportive care, standard chemotherapy regimens
      and novel chemotherapy combinations. Chemotherapy regimens containing gemcitabine
      therefore represent good value for money and efficient use of healthcare
      resources in the treatment of advanced NSCLC.

PMID- 11994043
TI  - The practice of splitting tablets: cost and therapeutic aspects.
AB  - BACKGROUND: Tablet splitting is used in pharmacy practice to adjust the dose to
      be administered. It is also being advocated as a method of reducing prescription
      drug costs. METHODS: The potential for using this practice as a cost-saving
      method was examined. The top 200 prescription products in Canada were evaluated
      for their potential for tablet splitting to reduce costs. The assessment was
      based on the dosage form (only tablets could be split), availability of dosages
      in multiples, whether the drug was used for long-term therapy, whether the
      product was packaged suitably (e.g. oral contraceptives in a therapeutic
      package), whether pricing structure would allow substantial saving, and the
      physical nature of the tablets (e.g. whether there were special dose-release
      characteristics). The products most commonly split in three Canadian pharmacies
      were compared with the products that had a substantial savings potential. Costs
      for splitting tablets in the pharmacy and costs of instructing patients to split
      tablets were calculated. RESULTS: Savings could be generated from tablet
      splitting for only 15 of the 200 products. There was little overlap between these
      15 products and the products that were most frequently split in the three
      pharmacies. The costs associated with tablet splitting in the pharmacy were
      approximately 0.1 Canadian dollars ($Can) per tablet. The cost of instructing a
      patient to split the tablets was approximately $Can1. CONCLUSIONS: Tablet
      splitting appears to have limited usefulness as a cost-reduction strategy. Only a
      small proportion of products are suitable for splitting and have the potential
      for savings. There are also costs arising from splitting tablets in the pharmacy,
      or instructing patients to do so, and from wastage of product. There are also
      issues such as patient compliance and the risk of an incorrect dose being taken
      that should be considered.

PMID- 11994044
TI  - The cost of gastro-oesophageal reflux disease, dyspepsia and peptic ulcer disease
      in Sweden.
AB  - BACKGROUND AND OBJECTIVE: Dyspepsia, peptic ulcer disease (PUD) and gastro
      oesophageal reflux disease (GORD) involve a substantial cost to Swedish society.
      There is a lack of up-to-date nationwide cost estimates after 1985. This study
      was conducted to present a comprehensive and updated cost analysis and study the
      change over time of the national cost of these disorders. DESIGN AND SETTING:
      Primarily, data from National Swedish databases and secondly, data from databases
      from the County of Uppsala for 1997 were used for the calculations and
      estimations. PERSPECTIVE: Swedish societal perspective. RESULTS: The total cost
      to Swedish society of dyspepsia, PUD and GORD in 1997 was $US424 million, or
      $US63 per adult. Direct costs totalled $US258 million (61%) while indirect costs
      totalled $US166 million (39%). The highest proportions of costs were due to drugs
      and sick leave, these being 37 and 34%, respectively. CONCLUSIONS: The cost of
      dyspepsia and GORD is substantial for patients, health providers and society.
      Since 1985, drug costs have increased substantially while the cost of sick leave
      has decreased.

PMID- 11994045
TI  - Phosphorylation and activation of mitogen- and stress-activated protein kinase-1
      in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires
      both extracellular-signal-regulated kinase and p38 mitogen-activated protein
      kinase.
AB  - G-protein-coupled receptor agonists are powerful stimulators of mitogen-activated
      protein kinase (MAPK) cascades in cardiac myocytes. However, little is known
      regarding the physiological activation of enzymes downstream of MAPKs. We
      examined the activation of mitogen- and stress-activated protein kinase-1 (MSK1),
      a downstream target of MAPKs, in adult rat cardiac myocytes by phenylephrine and
      endothelin-1. Both agonists induced the phosphorylation of MSK1 at Thr-581 and
      Ser-376 but not at Ser-360. Maximal phosphorylation was observed at 10-15 min
      after stimulation and it correlated with increased activity. Maximal activation
      of MSK1 in adult cardiomyocytes temporally coincided with maximal p38 MAPK
      activation while activation of the extracellular-signal-regulated kinase (ERK)
      cascade was more rapid. Phosphorylation and activation of MSK1 was completely
      inhibited by either PD98059 (ERK1/2 pathway inhibitor) or SB203580 (p38 MAPK
      inhibitor) alone. These data demonstrate that MSK1 activation in adult rat
      cardiac myocytes by G-protein-coupled receptor agonists requires the simultaneous
      activation of both the ERK and p38 MAPK pathways. However, the lack of
      phosphorylation at Ser-360, an identified phosphorylation site targeted by MAPKs,
      may indicate that MSK1 is not a direct substrate of ERK1/2 and p38 MAPK in adult
      rat cardiomyocytes.

PMID- 11994046
TI  - Oxidation of nitric oxide by oxomanganese-salen complexes: a new mechanism for
      cellular protection by superoxide dismutase/catalase mimetics.
AB  - Manganese-salen complexes (Mn-Salen), including EUK-8 [manganese N,N'
      bis(salicylidene)ethylenediamine chloride] and EUK-134 [manganese 3-methoxy N,N'
      bis(salicylidene)ethylenediamine chloride], have been reported to possess
      combined superoxide dismutase (SOD) and catalase mimetic functions. Because of
      this SOD/catalase mimicry, EUK-8 and EUK-134 have been investigated as possible
      therapeutic agents in neurological disorders resulting from oxidative stress,
      including Alzheimer's disease, Parkinson's disease, stroke and multiple
      sclerosis. These actions have been explained by the ability of the Mn-Salen to
      remove deleterious superoxide (O(2)(-)) and H(2)O(2). However, in addition to
      oxidative stress, cells in models for neurodegenerative diseases may also be
      subjected to damage from reactive nitrogen oxides (nitrosative stress), resulting
      from elevated levels of NO and sister compounds, including peroxynitrite (ONOO(
      )). We have been examining the interaction of EUK-8 and EUK-134 with NO and ONOO(
      ). We find that in the presence of a per-species (H(2)O(2), ONOO(-), peracetate
      and persulphate), the Mn-Salen complexes are oxidized to the corresponding oxo
      species (oxoMn-Salen). OxoMn-Salens are potent oxidants, and we demonstrate that
      they can rapidly oxidize NO to NO(2) and also oxidize nitrite (NO(2)(-) to
      nitrate (NO(2)(-)). Thus these Mn-Salens have the potential to ameliorate
      cellular damage caused by both oxidative and nitrosative stresses, by the
      catalytic breakdown of O(2)(-), H(2)O(2), ONOO(-) and NO to benign species: O(2),
      H(2)O, NO(2)(-) and NO(3)(-).

PMID- 11994047
TI  - Pivotal role of superoxides generated in the mitochondrial respiratory chain in
      peroxynitrite-dependent activation of phospholipase A2.
AB  - Exposure of PC12 cells to reagent peroxynitrite promotes the release of
      arachidonic acid (AA) mediated by activation of phospholipase A(2) [Guidarelli,
      Palomba and Cantoni (2000) Br. J. Pharmacol. 129, 1539-1542]. We now present
      experimental evidence consistent with the notion that this response is not
      directly triggered by peroxynitrite but, rather, by reactive oxygen species
      generated at the level of complex III of the mitochondrial respiratory chain. In
      particular, superoxide (and not hydrogen peroxide) has a pivotal role in
      peroxynitrite-dependent activation of phospholipase A(2). This observation was
      confirmed by results showing that superoxide, or peroxynitrite, promotes release
      of AA in isolated mitochondria. Consistently, the release of AA elicited by
      either peroxynitrite or A23187 in intact cells was shown to be calcium-dependent
      and differentially affected by phospholipase A(2) inhibitors with different
      levels of specificity. In particular, the effects of peroxynitrite, unlike those
      of A23187, were both sensitive to low concentrations of two general phospholipase
      A(2) inhibitors and insensitive to arachidonyltrifluoromethyl ketone, which shows
      some selectivity towards cytosolic phospholipase A(2). In addition, peroxynitrite
      and A23187 synergistically enhanced the release of AA. Collectively, the above
      results demonstrate that peroxynitrite causes inhibition of complex III, followed
      by enforced formation of superoxides that stimulate the activity of a calcium
      dependent PLA(2) isoform, probably localized in the mitochondria.

PMID- 11994048
TI  - Thermal denaturation of influenza virus and its relationship to membrane fusion.
AB  - The X-31 strain of influenza virus was studied by differential scanning
      calorimetry (DSC), CD and SDS/PAGE analysis as a function of both temperature and
      pH. A bromelain-treated virus was also studied by these methods. The major
      transition observed in the intact virus was a result of the denaturation of the
      haemagglutinin (HA) protein. At pH 7.4, this transition was similar in the intact
      virus and the isolated HA, but was absent in the bromelain-treated virus.
      However, at pH 5 the denaturation temperature and enthalpy were both higher for
      HA in the virus than in the isolated protein, indicating that HA interacts with
      other molecular components in the intact virus. The transition observed by DSC
      occurs at a higher temperature than does the thermal transition observed by CD.
      The temperature of the CD transition coincides with the temperature at which the
      fusogenicity of the virus increases, and probably corresponds to the formation of
      an extended coiled-coil conformation. Analysis by SDS/PAGE at neutral pH under
      non-reducing conditions demonstrates a selective loss of the HA protein trimer,
      resulting in the formation of aggregates in the range of temperatures of 55 to 70
      degrees C. In contrast, at acidic pH, the HA protein is largely in the monomeric
      form at 25 degrees C, and there is little change with temperature. There is thus
      a weakening of the quaternary structure of HA at acidic pH prior to heating. At
      the temperature at which the virus exhibits an increased fusogenicity at neutral
      pH, there is a loss of secondary structure and a beginning of a destabilization
      of the trimeric form of HA. This temperature is lower than that required for the
      major endothermic peak observed in DSC experiments. The results demonstrate that
      there is no kinetically trapped high-energy form of HA at neutral pH.

PMID- 11994049
TI  - Identification and characterization of the gene encoding the human
      phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional
      enzyme (CoA synthase).
AB  - The final two enzymes in the CoA biosynthetic pathway, phosphopantetheine
      adenylyltransferase (PPAT; EC 2.7.7.3) and dephospho-CoA kinase (DPCK; EC
      2.7.1.24), are separate proteins in prokaryotes, but exist as a bifunctional
      enzyme in pig liver. In the present study we have obtained sequence information
      from purified pig-liver enzyme, and identified the corresponding cDNA in a number
      of species. The human gene localizes to chromosome 17q12-21 and contains regions
      with sequence similarity to the monofunctional Escherichia coli DPCK and PPAT.
      The recombinant 564-amino-acid human protein confirmed the associated transferase
      and kinase activities, and gave similar kinetic properties to the wild-type pig
      enzyme.

PMID- 11994050
TI  - Lead poisoning: case studies.
AB  - Early clinical features of lead toxicity are non-specific and an occupational
      history is particularly valuable. Lead in the body comprises 2% in the blood
      (t1/2 35 days) and 95% in bone and dentine (t1/2 20-30 years). Blood lead may
      remain elevated for years after cessation from long exposure, due to
      redistribution from bone. Blood lead concentration is the most widely used marker
      for inorganic lead exposure. Zinc protoporphyrin (ZPP) concentration in blood
      usefully reflects lead exposure over the prior 3 months. Symptomatic patients
      with blood lead concentration >2.4 micromol l-1 (50 microg dl-1) or in any event
      >3.8 micromol l-1 (80 microg dl-1) should receive sodium calciumedetate i.v.,
      followed by succimer by mouth for 19 days. Asymptomatic patients with blood lead
      concentration >2.4 micromol l-1 (50 microg dl-1) may be treated with succimer
      alone. Sodium calciumedetate should be given with dimercaprol to treat lead
      encephalopathy.

PMID- 11994051
TI  - Population pharmacokinetics model and limited sampling strategy for intravenous
      vinorelbine derived from phase I clinical trials.
AB  - AIMS: a) To characterize the pharmacokinetics of intravenous vinorelbine, b) to
      use a population analysis for the identification of patient covariates that might
      appreciably influence its disposition and c) to define a limited sampling
      strategy for further Bayesian estimation of individual pharmacokinetic
      parameters. METHODS: All data were collected from 64 patients (99 courses)
      entered in three different phase I trials that have been previously reported. All
      patients received vinorelbine as a 20 min infusion with dose levels ranging from
      20-45 mg m-2. The population pharmacokinetic model was built in a sequential
      manner on a subset of two-thirds of the data, starting with a covariate-free
      model then progressing to a covariate model using the nonlinear-mixed effect
      methodology. The remaining one-third of the data were used to validate several
      sparse sampling designs. RESULTS: A linear three-compartment model characterized
      vinorelbine blood concentrations (n=1228). Two primary pharmacokinetic parameters
      (total clearance and volume of distribution) were related to various combinations
      of covariates. The relationship for total clearance (CLtotal (l h-1)=29.2xBSAx(1
      0.0090 Plt)+6.7xWt/Crs) was dependent on the patient's body surface area (BSA),
      weight (Wt), serum creatinine (Crs) and platelet count before administration
      (Plt). The optimal limited sampling strategy consisted of a combination of three
      measured blood concentrations; the first immediately before the end of infusion
      or 20 min later, the second at either 1 h, 3 h or 6 h and the third at 24 h after
      drug administration. CONCLUSIONS: A population pharmacokinetic model and a
      limited sampling strategy for intravenous vinorelbine have been developed. This
      is the first population analysis performed on the basis of a large phase I
      database that has identified clinical covariates influencing the disposition of
      i.v. vinorelbine. The model can be used to obtain accurate Bayesian estimates of
      pharmacokinetic parameters in situations where extensive pharmacokinetic sampling
      is not feasable.

PMID- 11994052
TI  - Metformin does not enhance ovulation induction in clomiphene resistant polycystic
      ovary syndrome in clinical practice.
AB  - AIMS: To determine whether metformin pretreatment has beneficial effects in
      clomiphene resistant infertile women with polycystic ovary syndrome (PCOS) in an
      infertility clinic. METHODS: This was a randomized placebo controlled double
      blind crossover study of 3 months metformin (1500 mg day-1)/placebo, followed by
      3 months metformin/placebo together with clomiphene (50-100 mg for 5 days) for
      three cycles in clomiphene resistant women with PCOS. The primary outcomes were
      restoration of spontaneous menses, ovulation induction (spontaneous or clomiphene
      induced) and pregnancy. Secondary endpoints were changes in biochemical
      parameters related to androgens and insulin. RESULTS: Twelve women completed the
      metformin arm and 14 the placebo arm. Spontaneous menstruation resumed in five
      metformin treated patients and in six placebo treated women, P=0.63. No women
      given metformin spontaneously ovulated, although one patient given placebo did,
      P=0.30. There was no difference in the efficacy of clomiphene between the two
      groups with ovulation being induced in five (out of 12) metformin treated women
      and four (out of 14) placebo treated women, P=0.63. Pregnancy occurred in three
      (out of 12) women given metformin and two (out of 14) women given placebo,
      P=0.59. CONCLUSIONS: Metformin is not always beneficial when given to clomiphene
      resistant infertile women with PCOS in clinical practice.

PMID- 11994053
TI  - Pharmacokinetic/pharmacodynamic model for prednisolone inhibition of whole blood
      lymphocyte proliferation.
AB  - AIMS: Mitogen-induced ex vivo whole blood lymphocyte proliferation (WBLP) is a
      widely used method to assess lymphocyte responsiveness to immunosuppressive
      therapy. A three-component complex model was developed to characterize effects of
      prednisolone on cell trafficking, transduction, and lymphocyte suppression.
      METHODS: An oral dose (0.27 mg kg-1) of prednisone was given to 32 subjects. The
      study consisted of baseline and prednisone phases each with 32 h of sampling.
      Measurements included plasma prednisolone concentrations, in vitro and ex vivo
      WBLP, and lymphocyte cell counts during baseline and prednisone phases. RESULTS:
      The final model consists of a precursor-dependent indirect response model with a
      first-order periodic influx rate for lymphocyte trafficking. This accounts for
      the rebound phenomenon and the circadian rhythm seen in all individual ex vivo
      WBLP effect-time profiles. Prednisolone was modelled as inhibiting lymphocyte
      influx from the precursor to the blood pools. The direct suppressive effect of
      prednisolone on WBLP was modelled with the simple Imax model. A transduction step
      with rate constant kt was introduced to the simple Imax model to account for the
      delay ( approximately 4 h) in reaching the maximum inhibition. The IC50 values
      obtained ex vivo were circa 10 times lower than in vitro values (3.76 vs 38.8 ng
      ml-1), suggesting additional in vivo factors may have enhanced lymphocyte
      response to the inhibitory effect of prednisolone. CONCLUSIONS: This integrated
      PK/PD model enables evaluation of multicomponent direct and indirect inhibition
      of ex vivo WBLP by steroids and other immunosuppressants in relation to sex and
      race.

PMID- 11994054
TI  - Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady
      state pharmacokinetics and pharmacodynamics of warfarin.
AB  - AIMS: To investigate the influence of a multiple-dose regimen with the catechol-O
      methyltransferase inhibitor entacapone on the pharmacokinetics and
      pharmacodynamics of warfarin. METHODS: In a randomized, double-blind, two-way
      cross-over study, 12 healthy subjects (gender ratio 1 : 1) received treatment for
      1 week with either entacapone 200 mg four times daily or placebo during
      individually optimized treatment with warfarin (INR 1.4-1.8). The effect of
      entacapone on the steady-state pharmacokinetics of both R- and S-warfarin was
      determined and, in addition, INR values were measured. The key pharmacokinetic
      variables were AUCss, Cmax and tmax. RESULTS: Entacapone increased the exposure
      to R-warfarin by 18% (90% CI: 111, 126%), and caused a 13% (6, 19%) increase in
      INR values. No effect was seen on the pharmacokinetics of the pharmacologically
      more potent S-enantiomer. Safety and tolerability variables did not show any
      difference between the treatment phases. CONCLUSIONS: In healthy subjects,
      entacapone displays a slight pharmacokinetic interaction with R-warfarin but,
      based on the lack of a clinically relevant pharmacodynamic interaction, it
      appears that it can also be used safely in Parkinson's disease patients who are
      receiving warfarin.

PMID- 11994055
TI  - Dose-finding and efficacy study for i.m. artemotil (beta-arteether) and
      comparison with i.m. artemether in acute uncomplicated P. falciparum malaria.
AB  - AIMS: The antimalarial efficacy/pharmacodynamics and pharmacokinetics of
      intramuscular (i.m.) artemotil in Thai patients with acute uncomplicated
      falciparum malaria were studied to determine effective dose regimens and to
      compare these with the standard dose regimen of artemether. METHODS: In part I of
      the study three different artemotil dose regimens were explored in three groups
      of 6-9 patients for dose finding: 3.2 mg kg-1 on day 0 and 1.6 mg kg-1 on days 1
      4 (treatment A), 1.6 mg kg-1 on day 0 and 0.8 mg kg-1 on days 1-4 (treatment B),
      3.2 mg kg-1 on day 0 and 0.8 mg kg-1 on days 1-4 (treatment C). In part II of the
      study, artemotil treatments A and C were compared in three groups of 20-22
      patients with standard i.m. artemether treatment: 3.2 mg kg-1 on day 0 and 0.8 mg
      kg-1 on days 1-4 (treatment R). RESULTS: Full parasite clearance was achieved in
      all patients in Part I, but parasite clearance time (PCT) and fever clearance
      time (FCT) tended to be longer in treatment B. Also the incidence of
      recrudescence before day 28 (RI) tended to be higher for treatment B. In part II,
      the mean PCT for each of the two artemotil treatments (52 and 55 h, respectively)
      was significantly longer than for artemether (43 h). The 95% CI for the
      difference A vs R was 0, 16 h (P=0.0408) and for difference C vs R it was 2, 19 h
      (P=0.0140). FCT was similar for the three treatments. The incidence of RI ranged
      from 5 out of 19 for treatment C to 3 out of 20 for treatment R. Plasma
      concentration-time profiles of artemotil indicated an irregular and variable rate
      of absorption after i.m. injection. A late onset of parasite clearance was
      associated with delayed absorption and/or very low initial artemotil plasma
      concentrations. Pharmacokinetic-pharmacodynamic evaluations supported a
      relationship between the rate of parasite clearance and exposure to artemotil
      during approximately the first 2 days of treatment, and suggested that artemotil
      has a slower rate of absorption than artemether. Safety assessment, including
      neurological and audiometric examinations showed no clinically relevant findings.
      Adverse events before and during treatment included headache, dizziness, nausea,
      vomiting and abdominal pain. These are characteristic of acute malaria infections
      and resolved during treatment. CONCLUSIONS: The optimum dose regimen for
      artemotil in this study was identical to the standard dose regimen of artemether.
      The findings that artemotil is more slowly absorbed from the i.m. injection site
      than artemether, and that early systemic availability may be insufficient for an
      immediate onset of parasite clearance contributed to the decision to choose a
      higher loading dose of artemotil (divided over two injection sites) and to omit
      the fifth dose in later studies. With this optimized dosing schedule, the more
      pronounced depot characteristics of i.m. artemotil can be an advantage, since it
      may allow shorter hospitalization.

PMID- 11994056
TI  - Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated
      intranasal spray. A study in healthy volunteers.
AB  - AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam
      administered as a concentrated intranasal spray, compared with intravenous
      midazolam, in healthy adult subjects. METHODS: Subjects were administered single
      doses of 5 mg midazolam intranasally and intravenously in a cross-over design
      with washout period of 1 week. The total plasma concentrations of midazolam and
      the metabolite 1-hydroxymidazolam after both intranasal and intravenous
      administration were described with a single pharmacokinetic model. beta-band EEG
      activity was recorded and related to midazolam plasma concentrations using an
      exponential pharmacokinetic/pharmacodynamic model. RESULTS: Administration of the
      intranasal spray led to some degree of temporary irritation in all six subjects,
      who nevertheless found intranasal administration acceptable and not painful. The
      mean (+/-s.d.) peak plasma concentration of midazolam of 71 (+/-25 ng ml-1) was
      reached after 14 (+/-5 min). Mean bioavailability following intranasal
      administration was 0.83+/-0.19. After intravenous and intranasal administration,
      the pharmacokinetic estimates of midazolam were: mean volume of distribution at
      steady state 1.11+/-0.25 l kg-1, mean systemic clearance 16.1+/-4.1 ml min-1 kg-1
      and harmonic mean initial and terminal half lives 8.4+/-2.4 and 79+/-30 min,
      respectively. Formation of the 1-hydroxymetabolite after intranasal
      administration did not exceed that after intravenous administration. CONCLUSIONS:
      In this study in healthy volunteers a concentrated midazolam nasal spray was
      easily administered and well tolerated. No serious complications of the mode of
      administration or the drug itself were reported. Rapid uptake and high
      bioavailability were demonstrated. The potential of midazolam given via a nasal
      spray in the acute treatment of status epilepticus and other seizure disruptions
      should be evaluated.

PMID- 11994057
TI  - Pharmacokinetics and pharmacodynamics of combination chemotherapy with paclitaxel
      and epirubicin in breast cancer patients.
AB  - AIMS: To investigate the pharmacokinetics and pharmacodynamics of epirubicin and
      paclitaxel in combination, as well as the effects of paclitaxel and its vehicle
      Cremophor EL on epirubicin metabolism. METHODS: Twenty-seven female patients with
      metastatic breast cancer received epirubicin 90 mg m-2 i.v. followed 15 min or 30
      h later by a 3 h i.v. infusion of paclitaxel 175, 200 and 225 mg m-2. Plasma
      concentrations of paclitaxel, epirubicin and epirubicinol were measured and the
      relationship between neutropenia and drug pharmacokinetics was evaluated using a
      sigmoid maximum effect (Emax) model. Finally, the influence of paclitaxel and
      Cremophor EL on epirubicin metabolism by whole blood was examined. RESULTS: An
      increase in epirubicinol plasma concentrations occurred after the start of the
      paclitaxel infusion, resulting in a significant increase in the area under the
      plasma concentration-time curve (AUC) of epirubicinol (+0.5 micromol l-1 h [95%
      CI for the difference: 0.29, 0.71],+0.66 micromol l-1 h [95% CI for the
      difference: 0.47, 0.85] and +0.82 micromol l-1 h [95% CI for the difference:
      0.53, 1.11] at paclitaxel doses of 175, 200 and 225 mg m-2, respectively),
      compared with epirubicin followed by paclitaxel 30 h later (0.61+/-0.1 micromol l
      1 h). A significant increase in epirubicin AUC (+0.74 micromol l-1 h [95% CI for
      the difference: 0.14, 1.34] and +1.09 micromol l-1 h [95% CI for the difference:
      0.44, 1.74]) and decrease in drug clearance (CLTB) (-25.35 l h-1 m-2[95% CI for
      the difference: -50.18, -0.52] and -35.9 l h-1 m-2[95% CI for the difference 
      63,4,-8,36]) occurred in combination with paclitaxel 200 and 225 mg m-2 with
      respect to the AUC (3.16+/-0.6 micromol l-1 h) and CLTB (74.4+/-28.4 l h-1 m-2)
      of epirubicin followed by paclitaxel 30 h later. An Emax relationship was
      observed between neutropaenia and the time over which paclitaxel plasma
      concentrations were equal to or greater than 0.1 micromol l-1 (tC0.1). The tC0.1
      value predicted to yield a 50% decrease in neutrophil count was 7.7 h. Finally,
      Cremophor EL markedly inhibited the metabolism of epirubicin to epirubicinol in
      whole blood. CONCLUSIONS: Paclitaxel/Cremophor EL affects the disposition of
      epirubicinol and epirubicin. Furthermore, the slope factor of the Emax
      relationship between neutropenia and tC0.1 of paclitaxel suggests that the drugs
      might also interact at the pharmacodynamic level.

PMID- 11994058
TI  - The roles of CYP2D6 and stereoselectivity in the clinical pharmacokinetics of
      chlorpheniramine.
AB  - AIMS: To examine the stereoselective disposition of chlorpheniramine and to
      evaluate the role of CYP2D6 in chlorpheniramine pharmacokinetics in humans.
      METHODS: Eight healthy volunteers (six extensive metabolizers with respect to
      CYP2D6 and two poor metabolizers) received a single 8 mg oral dose of rac
      chlorpheniramine either given alone or following administration of quinidine 50
      mg every 6 h for 2 days prior to the study day and every 6 h thereafter until the
      end of the study. Plasma concentrations of (S)-(+)- and (R)-(-)-enantiomers of
      chlorpheniramine were determined using liquid chromatography/mass spectrometry.
      RESULTS: In extensive metabolizers, mean Cmax was greater (12.55+/-1.51 ng ml-1vs
      5.38+/-0.44 ng ml-1) and CLoral was lower (0.49+/-0.08 l h-1 kg-1vs 1.07+/-0.15 l
      h-1 kg-1) for (S)-(+)- than for (R)-(-)-chlorpheniramine (P<0.005). For (S)-(+)
      chlorpheniramine, administration of quinidine, an inhibitor of CYP2D6, resulted
      in an increase in Cmax to 13.94+/-1.51 (P<0.01), a reduction in CLoral to 0.22+/
      0.03 l h-1 kg-1 (P<0.01), and a prolongation of elimination half-life from 18.0+/
      2.0 h to 29.3+/-2.0 h (P<0.001). Administration of quinidine decreased CLoral for
      (R)-(-)-chlorpheniramine to 0.60+/-0.10 l h-1 kg-1 (P<0.005). In CYP2D6 poor
      metabolizers, systemic exposure was greater after chlorpheniramine alone than in
      extensive metabolizers, and administration of quinidine resulted in a slight
      increase in CLoral. CONCLUSIONS: Stereoselective elimination of chlorpheniramine
      occurs in humans, with the most pharmacologically active (S)-(+)-enantiomer
      cleared more slowly than the (R)-(-)-enantiomer. CYP2D6 plays a role in the
      metabolism of chlorpheniramine in humans.

PMID- 11994059
TI  - MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate
      fexofenadine.
AB  - AIMS: The C3435T polymorphism in the human MDR1 gene is associated with lower
      intestinal P-glycoprotein expression, reduced protein function in peripheral
      blood cells and higher plasma concentrations of the P-glycoprotein substrate
      digoxin. Using fexofenadine, a known P-glycoprotein substrate, the hypothesis was
      tested whether this polymorphism also affects the disposition of other drugs in
      humans. METHODS: Ten Caucasian subjects homozygous for the wild-type allele at
      position 3435 (CC) and 10 individuals homozygous for T at position 3435
      participated in this study. A single oral dose of 180 mg fexofenadine HCl was
      administered. Plasma and urine concentrations of fexofenadine were measured up to
      72 h using a sensitive LC/MS method. In addition, P-glycoprotein function was
      assessed using efflux of the P-glycoprotein substrate rhodamine 123 from CD56+
      cells. Results Fexofenadine plasma concentrations varied considerably among the
      study population. However, fexofenadine disposition was not significantly
      different between the CC and TT groups (e.g. AUC(0,infinity) CC vs TT: 3567.1+/
      1535.5 vs 3910.1+/-1894.8 ng ml-1 h, NS; 95% CI on the difference -1364.9,
      2050.9). In contrast, P-glycoprotein function was significantly decreased in
      CD56+ cells of the TT compared with the CC group (rhodamine fluorescence CC vs
      TT: 45.6+/-7.2% vs 61.1+/-12.3%, P<0.05; 95% CI on the difference 5.6, 25.5).
      Conclusions In spite of MDR1 genotype-dependent differences in P-glycoprotein
      function in peripheral blood cells, there was no association of the C3435T
      polymorphism with the disposition of the P-glycoprotein substrate fexofenadine in
      this German Caucasian study population. These data indicate that other mechanisms
      including uptake transporter function are likely to play a role in fexofenadine
      disposition.

PMID- 11994060
TI  - Concomitant overdosing of other drugs in patients with paracetamol poisoning.
AB  - AIMS: Paracetamol is frequently involved in intended self-poisoning, and
      concomitant overdosing of other drugs is commonly reported. The purpose of the
      study was to investigate further concomitant drug overdose in patients with
      paracetamol poisoning and to evaluate its effects on the outcome of the
      paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive
      patients admitted with paracetamol poisoning were studied and concomitant drug
      intake was recorded. The relative risk of hepatic encephalopathy, death or liver
      transplantation, hepatic dysfunction, liver cell damage, and renal dysfunction
      associated with concomitant overdosing of other drugs was evaluated by
      multivariate analysis. RESULTS: Concomitant drug overdose was found in 207
      patients (31%, 95% confidence interval [CI] 27, 34%). Concomitant overdosing of
      benzodiazepines (99 cases), opioid analgesics (38 cases), acetylsalicylic acid
      (33 cases), and NSAID (32 cases) predominated. Concomitant benzodiazepine
      overdose was an independent risk factor in the development of hepatic
      encephalopathy (odds ratio [OR] 1.91; CI 1.00, 3.65) and renal dysfunction (OR
      1.81; CI 1.00, 3.22). Concomitant overdosing of opioid analgesics was a
      protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07,
      0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the
      development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver
      transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more favourable
      outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS:
      Concomitant overdosing of benzodiazepines or analgesics is frequent in patients
      admitted with paracetamol poisoning. Concomitant benzodiazepine or
      acetylsalicylic acid overdose was associated with more severe toxicity, whereas
      concomitant overdosing of opioid analgesics was associated with less toxicity.

PMID- 11994085
TI  - Optimizing sputum methodology.

PMID- 11994086
TI  - How good are carbohydrates as allergens?

PMID- 11994087
TI  - Is allergen avoidance effective?

PMID- 11994088
TI  - Latex allergy: towards immunotherapy for health care workers.
AB  - Latex allergy is an important allergic disease for which safe and readily
      available immunotherapy is currently lacking. Despite advances in latex glove
      technology and reduction in allergen content, there remains a core of severely
      allergic health care workers (HCW), particularly with concominant food allergy,
      for whom allergen avoidance is insufficient. Current experience with
      immunotherapy using crude latex extracts has shown an unacceptable level of local
      and systemic side-effects. Latex allergens are extremely potent with a heightened
      capacity to cross-link effector cell-bound IgE and induce anaphylaxis. The
      predominant pattern of allergen reactivity among HCW is different from that among
      children with spina bifida, perhaps due to exposure to latex glove proteins,
      particularly via inhalation, rather than particle bound latex proteins present in
      urinary catheters. Recent studies using purified skin testing reagents have
      indicated that the most clinically important latex allergens amongst HCW are Hev
      b 5, 6 and 7. Elucidation of the molecular and cellular mechanisms of the immune
      response to these allergens is pivotal to facilitate the search for safer
      immunotherapy of latex allergy among HCW.

PMID- 11994089
TI  - Sputum processing: a new method to improve cytospin quality.
AB  - BACKGROUND: Sputum examination is being increasingly used as a non-invasive
      method for studying airway inflammation. However, the application of sputum still
      presents some methodological problems and the results of sputum analysis may be
      substantially flawed by salivary contamination, cell and mucus debris. In
      addition, much work is needed to deepen the possibility of extensive application
      of cell and molecular biology techniques to sputum analysis. OBJECTIVE: In an
      attempt to improve the technique of sputum processing, we investigated the effect
      of: (i) 20 and 11 microm filtration in addition to 40 microm on salivary
      contamination; (ii) Percoll density gradient centrifugation on sputum slides
      quality; (iii) a culture medium (Minimum Essential Medium containing HEPES 22 mm,
      pH 7.4: MEM) as washing and suspension solution compared to PBS on cell
      viability. METHODS: Induced sputum samples were obtained in 37 asthmatics. 21
      samples were processed as selected sputum and 16 samples as entire expectorates.
      After dithiotreitol (DTT) homogenization, each specimen was aliquoted in two
      parts of equal volume. One portion was processed with the usual method, the other
      using a modified method: cell pellet was suspended in sterile MEM, filtered
      through 40, 20 and 11 microm net filters and separated from the residual debris
      by Percoll gradient centrifugation. RESULTS: As compared to the current sputum
      processing this method resulted in: (i) no selective bronchial cellular loss;
      (ii) a significant decrease of salivary contamination, particularly in entire
      expectorates in which squamous cells were reduced from 47 (36) to 15.5% (20) as
      median values and interquartile range; (iii) a higher proportion of good quality
      cytospins; (iv) maintenance of cell viability over the time (88% vs. 81% in MEM
      and PBS, respectively) 1 h after sample collection. CONCLUSION: In the present
      study we demonstrated that the proposed method is feasible and makes it possible
      to overcome most of the technical limits met with the commonly used method,
      pointing to a potential extension of induced sputum application for more
      sophisticated techniques.

PMID- 11994090
TI  - Repeated ozone exposures enhance bronchial allergen responses in subjects with
      rhinitis or asthma.
AB  - BACKGROUND: Single exposures to > 200 p.p.b. of ozone are capable of enhancing
      the early-phase lung function response to allergen. OBJECTIVE: The aim of the
      present study was to compare the effect of single vs. repeated exposures to ozone
      on early and late-phase allergen responses. METHODS: Eleven subjects with
      allergic asthma and 22 subjects with allergic rhinitis underwent single exposures
      to filtered air, 125 p.p.b. and 250 p.p.b. ozone, as well as repeated exposures
      to 125 p.p.b. ozone on four consecutive days. Twenty hours after the (final)
      exposure, subjects inhaled a single dose of allergen and a sputum induction was
      performed 6-7 h later. RESULTS: In the subjects with rhinitis, the mean early
      phase response of FEV1 and the number of > or = 20% reductions were significantly
      greater after exposure to 250 or 4 x 125 p.p.b. ozone compared with filtered air.
      In addition, most of the > or = 15% late-phase responses in FEV1 occurred after
      exposure to 4 x 125 p.p.b., as well as the strongest effects on sputum
      parameters. The rise in the number of eosinophils was statistically significant
      in both groups. Regarding the number of lymphocytes and the concentrations of
      mast cell tryptase, histamine or LDH, significance was, however, only reached in
      the asthma group. CONCLUSION: Our data suggest that repeated exposure to ozone,
      at a peak ambient air level, can enhance both functional and inflammatory
      responses to inhaled allergen in subjects with pre-existing allergic airway
      diseases, and that these effects might reach a clinically relevant magnitude.

PMID- 11994091
TI  - Pollutional and meteorological factors are closely related to complaints of non
      allergic, non-infectious perennial rhinitis patients: a time series model.
AB  - BACKGROUND: Epidemiological studies in the past have focused on meteorological
      conditions, pollution and pollen and their relationship with symptoms of
      bronchial hyper-reactivity, however, there are no epidemiological studies which
      examine a wide range of such factors and determine their role in nasal hyper
      reactivity. OBJECTIVE: To investigate whether environmental factors can influence
      symptomatology in non-allergic non-infectious perennial rhinitis (NANIPER)
      patients, who suffer primarily from nasal hyper-reactivity symptoms. METHODS: We
      studied 16 non-smoking NANIPER patients and seven non-smoking controls during a
      218-day study period (March-October) by means of daily symptom scores and visual
      analogue scales for the subsets patency, secretions and sneezing, and compared
      them to seven primary factors which affected 'symptoms' and 10 secondary factors
      which affected primary factors only. RESULTS: The mean symptom scores in the
      NANIPER and control groups were 2.17 and 0.13, respectively. In NANIPER, the
      highest correlations of primary factors with symptomatology were found for
      symptom scores and sneezing with minimum daytime temperature (r = -0.62 and 
      0.45, respectively), ozone and NO concentrations. Patency and secretions were
      associated with minimum daytime temperature (r = -0.39 and 0.32, respectively).
      Time series analysis, however, correcting for several confounders such as
      autocorrelated symptomatology, showed that minimum daytime temperature and
      daytime relative humidity made an independent contribution to symptoms. In the
      control group, correlations were much lower, though present. Time series analysis
      was not possible. CONCLUSIONS: We conclude that in a mild climate with relatively
      low levels of pollution, minor pollution and meteorological disturbances result
      in substantial changes in nasal reactivity symptoms in NANIPER patients, but not
      controls, irrespective of other factors such as allergy or infection.

PMID- 11994092
TI  - Paradoxical low nasal nitric oxide in nasal polyposis.
AB  - BACKGROUND: Nitric oxide (NO) is synthesized in the respiratory tract. Three
      isoforms of NO synthase have been described in man, with the inducible form
      related to inflammatory disease. In the paranasal sinuses constitutive production
      of nitric oxide has been demonstrated, with levels of 20-25 p.p.m. being found in
      sinus puncture. Nasal polyposis is a chronic inflammatory condition in which
      inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp
      epithelium. OBJECTIVES: 1. Measurement of upper airway nitric oxide in nasal
      polyposis patients compared with those with allergic rhinitis, and with normal
      controls. 2. To assess the effect of polyp treatment on nasal NO levels. METHODS:
      NO levels (parts per billion) were measured in nasal and pulmonary exhaled air
      using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the
      chemiluminescence principle. Eighty-two patients were studied: 44 with rhinitis,
      but without polyps, and 38 with nasal polyps. NO levels were compared with those
      of 20 normal controls. In 23 further polyp patients, levels were measured pre-
      and post-treatment and the changes were compared with alterations in polyp size,
      as assessed by rigid nasendoscopy. RESULTS: Nasal NO levels were significantly
      lower (Kruskal-Wallis, P = 0.000, chi2 = 27.5, d.f. = 3) in patients with polyps
      than those found in uncomplicated allergic rhinitis. NO levels were correlated
      directly with extent of polyposis as graded by the Lund-McKay index. Successful
      treatment, with reduction in polyp volume, was associated with a rise in NO
      levels (P = 0.042). CONCLUSION: NO levels are low in nasal polyposis, despite
      high levels of iNOS, possibly related to blockage of the ostiomeatal complex and
      failure of NO generated constitutively in the sinuses to reach the nasal airway.
      A rise in the NO levels is seen with successful polyp treatment, and is
      proportional to the reduction in endoscopically assessed polyp size, suggesting
      that with both medical and surgical therapy, the ostiomeatal complex obstruction
      is decreasing. We propose the following scenario. Nasal NO levels are the result
      of two processes: inducible NO production by inflamed nasal mucosa plus
      constitutive sinus mucosal production, detectable in normals. In uncomplicated
      allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when
      inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO
      levels fall because sinus NO makes the major contribution.

PMID- 11994093
TI  - Prevalence of wheeze, bronchial hyper-responsiveness and asthma in the elderly
      Chinese.
AB  - BACKGROUND: Asthma is a common health problem affecting patients of all ages.
      Because of the ease of sampling, epidemiological studies have concentrated mainly
      on the paediatric and general population. OBJECTIVE: This study aimed to
      determine the prevalence of wheeze, bronchial hyper-responsiveness and asthma
      amongst our elderly population and deduce any clinical and laboratory risk
      factors that might identify elderly asthmatics at an earlier stage. METHODS: Two
      thousand and thirty-two elderly Chinese aged > or = 70 years, randomly selected
      from a registered list of all recipients of Old Age and Disability Allowances in
      Hong Kong, were administered a questionnaire on lung health. Two hundred and
      fifty subjects were invited to attend our laboratory for skin tests and pulmonary
      function tests and 179 agreed. Of these, 173 (96.6%) and 176 (98.3%) had
      eosinophil count and serum IgE levels measured, respectively. Two definitions of
      asthma were used: (1) bronchial hyper-responsiveness (BHR) plus current wheeze,
      and (2) history of wheezing without previous diagnostic labels of emphysema or
      chronic bronchitis. RESULTS: Fifteen patients (out of 179: 8.4%) reported
      wheezing over the past 1 year. Fifty-one patients (28.5%) demonstrated BHR on
      spirometry or histamine challenge tests. Seven patients had both symptoms of
      wheezing and evidence of BHR. The prevalence of asthma using this definition is
      therefore 3.9% (95% CI 1.6-7.9%). Nine patients had symptoms of wheezing without
      previous diagnostic labels of chronic bronchitis or emphysema and, using this
      definition, the prevalence is 5.0% (95% CI 2.3-9.3%). Using multiple logistic
      regression studies, sex, social class, age, smoking habits, serum IgE levels and
      eosinophil counts did not predict a diagnosis of asthma using either definition.
      We found no association between a positive skin test and any respiratory symptoms
      or illnesses including asthma. CONCLUSION: Wheeze, bronchial hyper-responsiveness
      and asthma are prevalent amongst our elderly population. However, there were no
      identifiable demographic and laboratory risk factors in this study that may help
      us predict a diagnosis of asthma.

PMID- 11994094
TI  - Outcome of a latex avoidance program in a high-risk population for latex allergy 
      a five-year follow-up study.
AB  - BACKGROUND: Children with a shunted hydrocephalus are at highest risk for
      developing an immediate type allergy to latex. Limited data are available for
      preventive or therapeutical approaches. OBJECTIVE: To evaluate the effectiveness
      of latex avoidance, with special regard to status of sensitization and
      compliance. METHODS: In 1995, 131 children with a shunted hydrocephalus were
      screened for sensitization to latex by skin prick test and determination of
      specific IgE. Patients and parents were instructed on latex-avoiding strategies.
      Hospital physicians, family doctors and dentists were advised to perform further
      surgical and other medical interventions under latex-free conditions. In 2000,
      100 of these 131 patients were re-evaluated according to the same testing
      procedures. Special attention was directed at the extent prophylaxis had been
      performed. RESULTS: In 1995, 30/100 patients re-evaluable in 2000 proved
      sensitized to latex, 70 had negative testing results. In 2000, 64/70 patients
      were still negative, six had meanwhile developed latex-specific IgE. Seven out of
      thirty subjects with former positive testing had changes within the same RAST
      class, 20 showed a decline of at least one RAST-class, whereas in three cases an
      increase of latex-specific IgE was found. However, only 34 patients, mainly those
      being already sensitized, had thoroughly followed both medical and private
      prophylaxis. Within this group, 16 subjects (47.1%) had improved and another nine
      (26.5%) were still negative. Only three (8.8%) already previously sensitized
      patients presented with a further increase of latex-specific IgE. Medical
      prevention contributed more to the outcome than home prevention. No statistically
      significant correlation with latex-avoidance was observed, however, in previously
      unsensitized subjects. Underlying disease, atopy, number of operations, and age
      did not prove as significant variables. CONCLUSION: Secondary prevention results
      in a decrease of specific IgE in latex-sensitized patients with hydrocephalus.
      This is due to medical more than home prophylaxis. Sensitization obviously occurs
      mainly in early childhood, thus primary prevention remains to be the main target.

PMID- 11994095
TI  - Mouldy houses influence symptoms of asthma among atopic individuals.
AB  - BACKGROUND: The influence of current levels of indoor fungi on asthma is a
      controversial issue that needs to be resolved in order to advise patients
      appropriately. OBJECTIVE: To assess the seasonal variation in indoor fungal
      levels and the impact of these levels on asthma among mould-sensitized
      individuals. METHODS: Thirty-five young adults with current asthma and
      sensitization to fungi were visited four times over 1 year. At each home visit a
      questionnaire was administered and samples of dust and air were collected.
      Participants also recorded information on symptoms, peak expiratory flows (PEF)
      and medication use. Dust samples were analysed for house dust mite allergen (Der
      p 1) and total fungal biomass (ergosterol). Total and genus-specific fungal
      propagules were identified in air samples. Seasonal variation in allergen levels
      and significant independent effects of fungal levels on peak flow variability
      (PFV) were identified by repeated measures analysis of variance. RESULTS:
      Significant seasonal variations were observed in viable airborne fungi,
      ergosterol levels in the floor dust and PFV. PFV correlated significantly with
      symptom scores and the dose of reliever medication. PFV was also significantly
      associated with smoking and visible mould. The association between visible mould
      and PFV was independent of season, smoking and the dose of reliever medication.
      However, there was no association between total fungi, specific fungi or
      ergosterol and PFV. Der p 1 levels had no significant influence on asthma, even
      in HDM-sensitized individuals. CONCLUSIONS: Mouldy homes adversely influence
      asthma in asthmatics sensitized to fungi.

PMID- 11994096
TI  - Characterization and comparison of commercially available German and American
      cockroach allergen extracts.
AB  - BACKGROUND: In this study we examine the variability among unstandardized
      cockroach allergen extracts. METHODS: We obtained 24 aqueous and glycerinated
      cockroach allergen extracts from nine manufacturers. We used previously
      characterized cockroach extracts, E2-Cg and E2-Ca, as references. The modified
      ninhydrin assay was used to determine protein concentration of each extract.
      Relative potencies of extracts were determined by competition ELISA, using a
      human allergic serum pool. Bla g 1 and Bla g 2 levels of glycerinated German
      cockroach extracts were determined by ELISA using monoclonal antibodies. Extracts
      were also analysed by SDS-PAGE. RESULTS: Commercial cockroach allergen extracts
      had highly variable protein contents that were lower than the protein contents of
      the references. Electrophoretic data confirmed the presence of a variable number
      and intensity of protein bands in extracts among manufacturers. The relative
      potencies of the commercial extracts were between 10 and 782 BAU/mL for German
      cockroach and 10-250 BAU/mL for American cockroach. The mean Bla g 1 content of
      the commercial extracts was significantly lower than that of the reference (P =
      0.001). The mean Bla g 2 content of the commercial extracts was higher than that
      of the E2-Cg reference but the Bla g 2 levels were more variable compared to Bla
      g 1. In glycerinated German cockroach extracts, protein concentrations, relative
      potencies and specific allergen levels were significantly correlated (P < 0.001).
      CONCLUSION: Our tests indicate that commercially available cockroach allergen
      extracts are variable in protein content, electrophoretic banding patterns,
      relative potency and Bla g 2 levels. In glycerinated German cockroach extracts,
      protein concentrations, relative potencies and specific allergen levels were
      significantly correlated.

PMID- 11994097
TI  - Human T cells that have been conditioned by the proteolytic activity of the major
      dust mite allergen Der p 1 trigger enhanced immunoglobulin E synthesis by B
      cells.
AB  - BACKGROUND: We have previously demonstrated that the proteolytic activity of Der
      p 1 selectively cleaves human CD25, the 55 kDa alpha subunit of the IL-2
      receptor. As a result of cleavage of surface CD25, peripheral blood T cells
      produce less IFN-gamma and more IL-4, thereby leading to progressive polarization
      of the T cells towards a Th2 cytokine profile. Therefore, these observations
      underline the potential role of the proteolytic activity of Der p 1 in creating a
      microenvironment conducive for IgE synthesis. OBJECTIVE: To study the effect of T
      cells that have been conditioned by the proteolytic activity of Der p 1 on IgE
      synthesis by B cells. METHODS: We have examined this concept in experiments
      whereby T cells that have been exposed to either proteolytically active or
      inactive Der p 1 were cocultured with autologous B cells and IgE antibody
      synthesis was monitored. RESULTS: Here we demonstrate for the first time that
      coculturing T cells that have been in contact with proteolytically active Der p 1
      with autologous B cells leads to augmentation of IgE antibody responses.
      CONCLUSIONS: The proteolytic activity of Der p 1 conditions human T cells, which
      then become empowered to trigger enhanced IgE synthesis by B cells.

PMID- 11994098
TI  - Long-term safety and efficacy of nevirapine tolerance induction.
AB  - BACKGROUND: The most frequent side-effects due to nevirapine (Viramune), the
      first non-nucleoside HIV reverse transcriptase inhibitor introduced for clinical
      use, are cutaneous hypersensitivity reactions. In non-serious cases, tolerance
      induction can be proposed. OBJECTIVE: Describe the long-term safety and efficacy
      of tolerance induction to nevirapine. METHODS: Six HIV-infected patients started
      a tolerance 1 to 2 months after an episode of nevirapine hypersensitivity.
      Increasing doses of nevirapine (2.5, 10, 25, 100, 250 and 750 microg and 2.5, 5,
      10, 25, 50 and 100 mg) were given orally at half-hour intervals under strict
      medical surveillance and patients were followed up regularly. RESULTS: All but
      two of the patients tolerated this induction well. One had a mild and transient
      reaction on day 1; nevirapine was not stopped. One had a moderate to severe
      reaction one month later; nevirapine was stopped and he recovered fully. All
      other patients have been taking nevirapine for more than 3 months without any
      adverse reaction. CONCLUSION: Therefore, when no alternatives are available in
      severely ill and hypersensitive HIV-infected patients, tolerance induction is a
      possible therapeutic option.

PMID- 11994099
TI  - Determination of interleukin-5 secretion from drug-specific activated ex vivo
      peripheral blood mononuclear cells as a test system for the in vitro detection of
      drug sensitization.
AB  - BACKGROUND: In vitro detection of drug sensitization is still limited. The
      lymphocyte transformation test, which determines drug-specific proliferation, is
      the only in vitro test for detecting drug sensitization at the cellular level
      irrespective of the reaction's clinical phenotype. Accumulation of eosinophils
      following IL-5 secretion from drug-specific stimulated T cells is a
      characteristic histological feature of drug-induced skin eruptions. OBJECTIVE: We
      determined whether in vitro drug-specific activation of ex vivo peripheral blood
      mononuclear cells from 10 patients with drug-induced maculopapular exanthems and
      three patients with severe skin reactions results in secretion of IL-5, IL-10 or
      IFN-gamma and assessed the sensitivity and specificity of drug-specific IL-5
      secretion as a test system compared with the lymphocyte transformation test and
      patch tests. Furthermore, the subsets of CD4+ and CD8+ T cells involved in drug
      specific proliferation, IL-5 secretion and mRNA expression were examined in three
      patients. METHODS: Drug-specific proliferation of peripheral blood mononuclear
      cells in the lymphocyte transformation test was investigated by 3H-thymidine
      uptake, and culture supernatants taken after 5 days were analysed for IL-5, IL-10
      and IFN-gamma concentrations by ELISA technique. IL-5 mRNA expression was
      determined by RT-PCR. RESULTS: Drug-specific activation of peripheral blood
      mononuclear cells consistently resulted in IL-5 and to a lesser extent in IL-10
      and IFN-gamma secretion. The sensitivities of the patch test, lymphocyte
      transformation test and assessment of drug-specific IL-5 secretion for the
      detection of drug sensitization were 55%, 75% and 92%, respectively. CONCLUSION:
      These data suggest a role for the determination of drug-specific IL-5 secretion
      by ex vivo peripheral blood mononuclear cells for the in vitro detection of drug
      sensitization in drug-induced maculopapular exanthems.

PMID- 11994100
TI  - Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule
      expression via a CysLT1 receptor-mediated mechanism.
AB  - BACKGROUND: The mechanisms involved in eosinophil recruitment by cysteinyl
      leukotrienes (CysLTs) remain to be defined. OBJECTIVE: We investigated whether
      CysLTs LTC4, LTD4 and LTE4 could directly stimulate in vitro adhesion molecule
      expression and cell locomotion of blood eosinophils from atopic asthmatic donors.
      METHODS: Mab staining and FACS analysis were used to evaluate Mac-1 and LFA-1
      expression on eosinophils before and after CysLTs stimulation. Eosinophil
      locomotion was tested using a 48-well Boyden microchamber. RESULTS: CysLTs, at
      the concentrations of 1 and 10 nM, were able to significantly up-regulate Mac-1
      expression (P < 0.05, each comparison) but not LFA-1 expression (P > 0.05, each
      comparison). A dose-dependent, eosinophil chemotaxis was also induced by LTC4,
      LTD4 and LTE4 (0.1-10 nM) (P < 0.01, each comparison). Montelukast (0.01 nM to 10
      nM), a specific CysLT1 receptor antagonist, significantly down-regulated LTC4,
      LTD4 and LTE4-induced Mac-1 expression (P < 0.01, each comparison) and the CysLT
      induced eosinophil migration (P < 0.01, each comparison). In contrast,
      montelukast did not affect Mac-1 expression or cell migration when eosinophils
      were stimulated by the 'non-specific activators', such as fMLP or C5a (P > 0.05,
      each comparison). CONCLUSION: These data demonstrate that CysLTs are active in
      vitro in directly up-regulating human eosinophil functions involved in eosinophil
      recruitment. The down-regulation of Mac-1 expression and eosinophil chemotaxis by
      the potent and selective CysLT1 receptor antagonist montelukast indicated the
      specificity of the LTC4-, LTD4- and LTE4-induced response.

PMID- 11994101
TI  - Coding single nucleotide polymorphism in the high-affinity immunoglobulin E
      receptor b chain (FcepsilonRI-beta) gene is associated with immunoglobulin E
      receptor-mediated histamine release from basophils.
AB  - BACKGROUND: Our previous work on linkage analysis showed that histamine release
      from basophils to anti-IgE stimuli was linked to the gene marker of chromosome
      11q13, where the beta chain of the high-affinity receptor for IgE (FcepsilonRI
      beta) is located. OBJECTIVE: To evaluate the association between FcepsilonRI
      mediated histamine release from basophils and four bi-allelic single nucleotide
      polymorphisms of the FcepsilonRI-beta gene. METHODS: Phenotypes of asthma, such
      as maximal histamine release from basophils and atopy, were measured from 80
      randomly recruited asthmatic children. Polymorphisms of the FcepsilonRI-beta gene
      were determined by PCR-based methods. RESULTS: The polymorphism in exon 7,
      resulting in Glu to Gly substitution, was significantly associated with histamine
      release from basophils to anti-IgE stimuli, but not with total IgE levels and
      skin test responses to aeroallergens. CONCLUSION: This study supports a role for
      the FcepsilonRI-beta gene in the expression of high affinity IgE receptor
      mediated histamine release from basophils.

PMID- 11994102
TI  - Cystic fibrosis transmembrane conductance regulator gene mutations: do they play
      a role in the aetiology of allergic bronchopulmonary aspergillosis?
AB  - BACKGROUND: Previous work suggests that cystic fibrosis transmembrane conductance
      regulator (CFTR) gene mutations may be implicated in the aetiology of allergic
      bronchopulmonary aspergilosis (ABPA). OBJECTIVE: To compare the frequency of CF
      gene mutations in asthmatics with ABPA of varying severity with asthmatics who
      were skin prick test (SPT)-positive to Aspergillus fumigatus (Af) without
      evidence of ABPA and asthmatics SPT-negative to Af. METHODS: Thirty-one Caucasian
      patients with ABPA were identified, together with asthmatics SPT positive to Af
      without evidence of ABPA (n = 23) and SPT negative to Af (n = 28). Genomic DNA
      was tested for 16 CF mutations accounting for approximately 85% of CF alleles in
      Caucasian New Zealanders. RESULTS: Four (12.9%) ABPA patients were found to be
      carriers of a CF mutation (DeltaF508 n = 3, R117H n = 1), one (4.3%) asthmatic
      SPT positive to Af without ABPA (DeltaF508), and one (3.6%) asthmatic SPT
      negative to Af (R117H). All patients with a CF mutation had normal sweat chloride
      (< 40 mM). There was no significant difference between the frequency of CF
      mutations in the ABPA patients and asthmatics without ABPA. However, the
      frequency of CF mutations in the ABPA patients was significantly different (P =
      0.0125) to the expected carrier rate in the general population. CONCLUSION: These
      results lend further support to a possible link between CF mutations and ABPA.

PMID- 11994103
TI  - Interaction among human leucocyte antigen-peptide-T cell receptor complexes in
      cow's milk allergy: the significance of human leucocyte antigen and T cell
      receptor-complementarity determining region 3 loops.
AB  - BACKGROUND: Allergic individuals respond to only a few specific antigens,
      therefore allergic diseases are characterized by antigen specificity.
      Clarification of the mechanism of antigen specificity will lead to progress in
      the therapy of allergic diseases. OBJECTIVES: The purpose of this study is to
      determine the specific association among T cell epitopes, antigen-presenting
      molecules and T cell receptor (TCR), and to determine the TCR usage in the
      pathogenesis of allergies using antigen-specific T cell clones (TCCs). The
      results can clarify the mechanism of the antigen specificity of allergic
      diseases, and provide new therapeutic possibilities using analogue peptides.
      METHODS: Short-term T cell clones specific to beta-lactoglobulin (BLG) were
      established from peripheral blood mononuclear cells (PBMCs) collected from five
      patients allergic to cow's milk. We then identified the T cell epitopes and
      antigen-presenting molecules, and examined TCR usage. We also determined the
      sequence of the TCR-complementarity-determining region 3 (CDR3). RESULTS: Six
      TCCs established from the five patients recognized three different peptides, and
      BLGp97-117 was recognized by four of the six TCCs. BLGp101-112 (KYLLFCMENSAE) was
      the core sequence in the fragment. Sequence analysis of TCR by the RT-PCR method
      revealed a marked heterogeneity in TCR usage, and similar amino acid sequences
      were recognized in the CDR3 region. Four of the six TCCs recognized BLG in
      association with human leucocyte antigen (HLA)-DRB1*0405 as antigen-presenting
      molecules. CONCLUSION: We proposed the motif of the interaction between the HLA
      DRB1*0405 allele and antigen peptide, and suggested that HLA-DRB1*0405 is an
      immunoregulatory gene product for T cell responses to BLG.

PMID- 11994104
TI  - Boletus edulis: a digestion-resistant allergen may be relevant for food allergy.
AB  - BACKGROUND: Fungal components can cause allergic symptoms either through
      inhalation, ingestion or contact. Whereas respiratory allergy is thought to be
      induced by spores, allergic reactions following ingestion are attributed to other
      parts of the mushroom. Reports of food-related allergic reactions due to the
      edible mushroom Boletus edulis have occasionally been reported. OBJECTIVE: The
      aim of the study was to investigate whether separate allergens may be detected in
      alimentary allergy to Boletus edulis. METHODS: Sera of two subjects, one with
      recurrent anaphylaxis and the other with a predominantly oral allergy syndrome
      following ingestion of Boletus edulis, have been analysed by a time-course
      digestion assay using simulated gastric fluid and by SDS-PAGE immunoblotting.
      Sera of four Boletus edulis skin prick test-negative subjects and all without
      clinical symptoms to ingested Boletus edulis served as controls. RESULTS: In
      lyophilized Boletus edulis extract, at least four water-soluble proteins were
      detected, the most reactive at 55 kDa and at 80 kDa. Following the time-course
      digestion assay, IgE binding was found to a 75-kDa protein, but only if the sera
      of the subject with recurrent anaphylaxis was used. CONCLUSION: The data indicate
      that Boletus edulis can cause an IgE-mediated food allergy due to a digestion
      stabile protein at 75 kDa. No IgE immune response to this protein was detected in
      the serum of a subject with respiratory allergy and oral allergy syndrome to
      Boletus edulis nor in control sera.

PMID- 11994105
TI  - Carbohydrates expressed on Aspergillus fumigatus induce in vivo allergic Th2-type
      response.
AB  - BACKGROUND: The mould Aspergillus fumigatus (Af) causes several forms of Th2
      biased diseases such as Type I respiratory allergies. This mould contains
      abundant carbohydrates including glucan, chitin and galactomannan. However,
      little is known on whether these carbohydrates directly drive Th2 responses in
      vivo. OBJECTIVE: We sought to determine the relative role of carbohydrates
      expressed on crude extracts of Af in the induction of Th2-type antibody
      production and local eosinophila in mice. METHODS: Carbohydrates on native Af
      were destroyed by sodium metaperiodate under mild conditions. CBA/J mice were
      sensitized intranasally with native, periodate-treated or mock-treated Af.
      Histologic changes and production of Af-specific IgE, IgG1 and IgG2a, as well as
      serum total IgE were determined. Inhibition ELISA for Af-specific IgE was
      performed using periodate-treated Af as an inhibitor. RESULTS: Mice sensitized
      with periodate-treated Af displayed significant decreases in both total and
      specific IgE levels in comparison to mice sensitized with native or mock-treated
      Af. Furthermore, sensitization and subsequent challenge with periodate-treated Af
      significantly reduced the degree of eosinophil recruitment into the nasal mucosa,
      compared to the controls. On the other hand, competitive inhibition showed that
      periodate-treated Af could inhibit binding between native Af and specific IgE in
      a similar manner to that of native and mock-treated Af. CONCLUSION: These results
      suggest that carbohydrates on Af play a key role as internal adjuvants in
      inducing the allergic Th2-type response and are not the targets of the induced
      IgE response.

PMID- 11994106
TI  - Lipoteichoic acid from Staphylococcus aureus induces Th2-prone dermatitis in mice
      sensitized percutaneously with an allergen.
AB  - BACKGROUND: We found previously that lipoteichoic acid (LTA) from Staphylococcus
      aureus has the ability to induce Th2 cytokine production by peripheral blood
      mononuclear cells (PBMC) from patients with atopic dermatitis (AD). However, it
      is not known whether LTA can induce a Th2-dominant cytokine response in the skin
      of AD patients. OBJECTIVE: The purpose of this study was to determine the effects
      of LTA in mice sensitized percutaneously with a house dust mite antigen (MA)
      through barrier-disrupted skin, as an experimental animal model of AD. METHODS:
      Mice were sensitized with MA by a single topical application to barrier-disrupted
      abdominal skin. Seven days after the sensitization, the mice were challenged on
      the dorsal skin by LTA to elicit localized skin inflammation. The cytokine
      response in the dorsal skin was investigated by reverse transcription-polymerase
      chain reaction (RT-PCR) and immunohistological analysis. The infiltration of
      inflammatory cells in the skin was also observed by histological staining.
      RESULTS: Injection of LTA into the dorsal skin of MA-sensitized mice, which show
      a Th2-dominant cytokine response against the homologous antigen, increased the
      expression of mRNA for IFN-gamma, IL-4 and IL-5, but not IL-2. Immunohistological
      analysis demonstrated that levels of IFN-gamma, IL-4 and IL-5 transcripts
      corresponded with those of protein synthesis. In addition, the dorsal skin of MA
      sensitized mice challenged with LTA showed significantly increased numbers of
      neutrophils, eosinophils, mononuclear cells and mast cells compared with control
      mice challenged with LTA. CONCLUSION: These results suggest that LTA has the
      ability to induce localized Th2-prone dermatitis in an allergen-independent
      manner in the skin of AD patients and may explain the role of colonization with
      S. aureus in AD patients.

PMID- 11994107
TI  - Expression of Th1, Th2 and immunosuppressive cytokine gene transcripts in canine
      atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is a common inflammatory skin disease of humans and
      dogs. Human atopic dermatitis is associated with Th2-type responses, although Th1
      cytokines can be identified in chronic lesions. In contrast, tolerance to
      environmental allergens in healthy individuals is mediated by regulatory T cells.
      OBJECTIVE: This study examined the expression of the immunosuppressive cytokines
      TGF-beta and IL-10, the Th2-type cytokines IL-4 and IL-6, and the Th1-type
      cytokines IFN-gamma, TNF-alpha, IL-2, IL-12p35 and IL-12p40, in canine atopic
      dermatitis. MATERIALS AND METHODS: RNA was isolated from lesional atopic, non
      lesional atopic and healthy canine skin samples. Semi-quantitative reverse
      transcriptase polymerase chain reactions (RT-PCRs) were carried out using
      specific primers and one-way analyses of variance used to compare cytokine
      expression in each group. RESULTS: Canine atopic dermatitis was associated with
      over-expression of IL-4 mRNA and reduced transcription of TGF-beta compared with
      healthy skin (P < 0.05). Higher levels of IFN-gamma, TNF-alpha and IL-2 mRNA were
      seen in lesional compared with non-lesional and healthy skin (P < 0.05). There
      were no significant differences in IL-10, IL-6, IL-12p35 or IL-12p40
      transcription between the three groups. CONCLUSIONS: This is the first report to
      demonstrate that canine atopic dermatitis is associated with over-production of
      IL-4. Clinical tolerance in healthy individuals appears to be associated with TGF
      beta, although it is unclear if this reflects an active mechanism or simply non
      responsiveness of the immune system. Th1 cytokines may be induced by subsequent
      self-trauma and secondary infections in atopic skin. We believe that these
      results better characterize spontaneously occurring canine atopic dermatitis. We
      further propose that this should be investigated as a possible animal model of
      human atopic dermatitis.

PMID- 11994108
TI  - Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic
      disease.
AB  - BACKGROUND: Polyclonal cytokine responses following stimulation of T cells with
      mitogens or superantigens provides information on cytokine production from a wide
      range of T cells. Alternatively allergen-induced T cell responses can provide
      information on cytokine production by allergen-reactive T cells. While there is
      evidence of increased Th2 and reduced Th1 cytokine production following T cell
      stimulation with non-specific mitogens and superantigens, the evidence that Th1
      cytokine production to allergens is decreased in line with a postulated imbalance
      in Th1/Th2 responses is unclear, with studies finding decreased, no difference or
      increased IFN-gamma responses to allergens in atopic subjects. OBJECTIVE: To
      examine childhood polyclonal and allergen-induced cytokine responses in parallel
      to evaluate cytokine imbalances in childhood atopic disease. METHODS: PBMC
      cytokine responses were examined in response to a polyclonal stimulus,
      staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house
      dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin
      (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic
      disease (asthma, eczema and/or rhinitis) (atopic). RESULTS: Atopic children had
      significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13
      production to SEB superantigen stimulation when compared with non-atopic
      children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL
      5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in
      atopic children. CONCLUSION: We show that a polyclonal stimulus induces a reduced
      Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast,
      the allergen-induced cytokine responses in atopic children were associated with
      both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The
      increased Th1 response to allergen is likely to reflect prior sensitization and
      indicates that increases in both Th1 and Th2 cytokine production to allergens
      exists concomitantly with a decreased Th1 response to a polyclonal stimulus in
      atopic children.

PMID- 11994109
TI  - What, if any, is the value of septal surgery?

PMID- 11994110
TI  - Flexible nasendoscope with a disposable-sheath system versus standard
      nasendoscopy: a prospective, randomized trial.
AB  - There are no published guidelines for the sterilization of the flexible
      nasendoscope and various techniques exist. We have conducted a randomized,
      prospective, blinded trial of the barrier Endosheath system versus immersion in
      Cidex disinfectant. Using a visual analogue assessment, there were no differences
      at a 99% confidence interval (CI) between the two techniques from the nursing
      assistant and patient perspectives. Image quality was assessed blinded and no
      difference could be detected at a 99% CI. The Endosheath offers the advantage of
      increasing the productivity of each nasendoscope as the sterilization time is
      reduced. It also provides barrier protection against cross-contamination,
      including prion diseases.

PMID- 11994111
TI  - The influence of meteorological factors on the frequency of epistaxis.
AB  - This retrospective study aims to search out the influence of temperature,
      atmospheric pressure and humidity on the frequency of epistaxis. The study
      includes 701 patients who have suffered from epistaxis and have been treated in
      the ENT department of the University of Ioannina Hospital, during the years 1995
      and 1996. The statistical methods used are simple linear correlation and linear
      stepwise regression analysis. The results of simple correlation analysis showed
      that the daily number of epistaxes depends mainly on mean, maximum and minimum
      temperature and water vapour pressure. The corresponding correlation coefficients
      are statistically significant, indicating an influence of weather on epistaxis up
      to 9% of its total variance. By applying stepwise regression analysis, we managed
      to increase the linear correlation coefficient and the corresponding amount of
      variance of epistaxis explained by meteorological factors. This percentage was
      found to approach 20% for the cold period and 10% for the warm period of the
      year.

PMID- 11994112
TI  - Voice gains following thyroplasty may improve over time.
AB  - Type I thyroplasty for unilateral vocal fold paralysis restores voice. The
      purpose of this study was to evaluate measures of voice before thyroplasty, and
      at 3 months and 1 year after surgery. Of interest was whether vocal improvement
      in the first weeks after surgery was maintained or even enhanced over time. A
      total of 40 patients with unilateral paralysis underwent type I thyroplasty with
      or without arytenoid adduction. Perceptual, acoustic and aerodynamic measures of
      voice were studied. Perceptual analysis determined that optimal postoperative
      voice quality evolved over the first year. Acoustic indices of perturbation
      demonstrated progressive improvement over 12 months, whereas pitch and intensity
      ranges were increasingly extended. Postoperative glottal flow rates were
      normalized and phonation times were significantly longer, with benefits
      maintained over time. All perceptual, aerodynamic and acoustic measures of voice
      were improved 3 months after thyroplasty, with many measures further improved at
      1 year. Such findings provide evidence that voice outcome progressively evolves
      over the first 12 months after surgery.

PMID- 11994113
TI  - The role of computerized tomography in the preoperative assessment of chronic
      suppurative otitis media.
AB  - Twenty patients awaiting mastoid surgery for chronic suppurative otitis media
      underwent preoperative high resolution computerized tomography (CT) of the
      temporal bones. The CT scans were compared with the intraoperative findings. CT
      was helpful in determining the anatomy of the middle ear and mastoid, and
      accurately predicted the extent of the disease process in the sinus tympani and
      facial recess. However, it was unable to distinguish between cholesteatoma,
      mucosal disease and fluid, and it contributed little to the surgical management
      of the patients. This suggests that routine preoperative CT scanning of patients
      before uncomplicated virgin mastoid surgery is of questionable value.

PMID- 11994114
TI  - The potential of virtual laryngoscopy in the assessment of vocal cord lesions.
AB  - Virtual laryngoscopy is a useful adjunctive radiological tool in the assessment
      of laryngeal lesions. A total of 10 patients requiring direct laryngoscopy for
      the investigation of laryngeal lesions underwent preoperative virtual
      laryngoscopy using three-dimensional reconstruction of two-dimensional
      computerized tomography (CT) images. All lesions were correctly diagnosed on
      virtual laryngoscopy before direct laryngoscopy. Its main advantages are that it
      does not require general anaesthesia, it allows three-dimensional visualization
      of the airway beyond areas of narrowing and it gives a highly accurate
      representation of vocal cord lesions, both in terms of definition and spatial
      representation. Its disadvantages are that it does not provide histology, it
      requires an air-mucosa interface to produce an image and it cannot identify
      functional lesions of the vocal cords.

PMID- 11994115
TI  - The radiological anatomy of the anterior skull base.
AB  - Two complications dominate the thoughts of any surgeon undertaking functional
      endoscopic sinus surgery (FESS), namely damage to orbital structures and
      fractures of the fovea ethmoidalis. To avoid these complications, a detailed
      knowledge of the paranasal sinus anatomy of the patient is essential. This is
      usually assessed using preoperative computerized tomography (CT) scans of the
      paranasal sinuses. Analysis of 151 CT scans, measuring the height of cribriform
      plate below a supraorbital horizontal and above the hard palate was performed.
      Variation of shape and take-off angle of the fovea ethmoidalis was also measured.
      Comparison between left and right sides, and between scans showing radiological
      features of sinonasal disease and normal scans, was undertaken. Five patterns of
      fovea ethmoidalis were identified. No statistically significant difference
      between left and right sides was demonstrable for any parameter, irrespective of
      pathological status.

PMID- 11994116
TI  - Contralateral suppression of DPOAE measured in real time.
AB  - The aim of this study was to measure contralateral suppression of distortion
      product otoacoustic emissions (DPOAE) in real time. A total of 10 human subjects
      were studied with a novel device to record DPOAE without signal time averaging,
      using digital narrow band pass filtering. Real time DPOAE levels were recorded at
      2f1-f2 using primary tone settings of f2/f1 = 1.22 and L1 = 70 dB SPL, L2 = 65 dB
      SPL, at five values of f2 between 2.2 and 7.7 kHz. An acoustic stimulus was
      applied intermittently to the contralateral ear to cause DPOAE suppression.
      Characteristic features of contralateral suppression were identified and
      distinguished from small spontaneous variations in the real time DPOAE signal.
      Magnitude of suppression increased with contralateral stimulus intensity. Onset
      latency of suppression was around 43 ms (31-95 ms). Potential clinical
      applications are discussed in the light of these findings, including a role in
      improving the specificity of neonatal hearing screening.

PMID- 11994117
TI  - Management of otosclerosis in the UK.
AB  - The last 30 years has seen a gradual change in the management of otosclerosis.
      The aim of this study is to evaluate the current practice among British
      otolaryngology consultants using a questionnaire, and to compare it with the
      practice reported in a survey 8 years ago. A total of 353 valid responses (64.5%)
      were available for analysis. The overall trend is towards centralization, with a
      reduction in the number of surgeons undertaking stapes surgery (49.9%). The
      majority of consultants (81.3%) who undertake stapes surgery would operate for a
      unilateral conductive loss and 75.1% would undertake bilateral stapes surgery.
      Stapedotomy is the operation of choice (82%), with a few consultants performing
      partial or rarely total stapedectomies. Postoperative restrictions and follow-up
      times vary widely amongst surgeons, with the senior surgeons tending to be more
      conservative than the younger consultants.

PMID- 11994118
TI  - Somatostatins and their role in thyroid cancer.
AB  - Somatostatins are neuropeptides that exert a downregulatory effect on various
      physiological processes. Somatostatin analogues are used in the imaging and
      management of various tumour types. Their role in thyroid cancer has not as yet
      been fully elucidated. A systematic review of the literature using the keywords
      thyroid, cancer and somatostatin revealed 263 references. This paper summarizes
      the current knowledge of the role of somatostatins in thyroid cancer and assesses
      their future potential.

PMID- 11994119
TI  - Head shaking nystagmus in the follow-up of patients with vestibular diseases.
AB  - We examined 420 patients with vestibular diseases of different origin; 273 with
      peripheral vestibular disease and 147 with both peripheral and central vestibular
      disease. Recurrent vestibulopathy like Meniere's disease, or benign paroxysmal
      positional vertigo, were not included. Patients were evaluated initially and 6
      months after pharmacological and/or rehabilitation therapy. At the initial
      assessment, the head-shaking test was specific for the side of the lesion in both
      groups, even if spontaneous nystagmus was no longer present. Thus, head-shaking
      nystagmus is a physical sign that can be easily evoked and gives useful
      information about the presence of vestibulo-ocular reflex asymmetry. At the
      follow-up at 6 months, many changes in the head-shaking nystagmus were noted: in
      some cases it appeared, in some others it changed direction and more often it
      disappeared. There is actually no acceptable explanation for the disappearance of
      the head-shaking nystagmus, despite some evidence that vestibular compensation
      could play a role. It is definitely proved that sensitivity of the head-shaking
      test is really poor, especially in the course of time and, therefore, it should
      not be used alone in the follow-up of patients with vestibular disease.

PMID- 11994120
TI  - Bone resorption after alloplastic augmentation of the mandible.
AB  - Augmentation mentoplasty is a commonly performed operation especially in
      conjunction with rhinoplasty. While various materials have previously been used
      for this procedure, silastic has been the implant of choice for the last three
      decades. Concerns have been raised due to the occurrence of bone resorption
      beneath these implants. Controversy prevails as to the cause and the long-term
      effects of the resorption. It has been suggested by some that the resorption is
      self-limiting although this has not been confirmed in clinical studies. In total,
      40 patients with silastic implants, who had a mean follow-up of 20 months (8-60
      months), were studied radiologically. In 21 of them (52%), a degree of resorption
      from 0.5 to 2 mm was observed. Spearman's rank correlation showed a statistically
      significant relationship between the degree of resorption and the time lapse
      since surgery (P = 0.048).

PMID- 11994121
TI  - Expression of BCL-2 via adeno-associated virus vectors rescues thalamic neurons
      after visual cortex lesion in the adult rat.
AB  - Lesions of the mammalian visual cortex cause the retrograde degeneration of the
      thalamic neurons projecting to the damaged cortex. The proto-oncogene bcl-2 is
      known to inhibit neuronal apoptosis induced by a variety of noxious stimuli and
      preserve the functional integrity of the injured cells. Here we have tested
      whether the overexpression of bcl-2 via adeno-associated virus (AAV) vectors is
      able to protect the neurons in the lateral geniculate nucleus after visual cortex
      ablation in adult rats. Recombinant AAV vectors encoding Bcl-2 (AAV-Bcl-2) or
      green fluorescent protein (AAV-GFP) as a control were stereotaxically injected
      into the geniculate. Three weeks after vector injection, the ipsilateral visual
      cortex was removed by aspiration, and cell survival was assessed 2 weeks later.
      We found that 20% of the geniculate neurons were transduced by the Bcl-2 vector.
      These cells were completely protected from death following cortical ablation.
      Delivery of AAV-GFP transduced an identical number of geniculate neurons but had
      no effect on cell survival after lesion. The total number of surviving geniculate
      neurons was found to be significantly higher in animals injected with AAV-Bcl-2
      than in rats injected with AAV-GFP or in control lesioned rats. These data
      indicate that Bcl-2 gene therapy with AAV vectors represents an effective
      treatment to promote neuronal survival after central nervous system insults.

PMID- 11994122
TI  - Effect of halothane on neuronal excitation in the superficial dorsal horn of rat
      spinal cord slices: evidence for a presynaptic action.
AB  - The action of the volatile anaesthetic halothane on optically recorded neuronal
      excitation in juvenile rat spinal cord slices was investigated. Prolonged
      neuronal excitation lasting approximately 100 ms was evoked in the superficial
      dorsal horn after single-pulse dorsal root stimulation that activated both A- and
      C-fibres. Halothane depressed the neuronal excitation in a concentration
      dependent manner (IC(50) 0.21 mm, I(max) 28%). In Ca(2+)-free solution, dorsal
      root stimulation induced excitation with a short duration of several tens of
      milliseconds, in which the excitation of the postsynaptic component was largely
      eliminated. Under these conditions, halothane also depressed the excitation
      concentration-dependently (IC(50) 0.46 mm, I(max) 60%). Most of the suppression
      occurred within 5 min of halothane application, and the effect of halothane was
      fully reversible upon washout of the anaesthetic. Application of bicuculline and
      strychnine or picrotoxin, or reduction of extracellular Cl(-) concentration ([Cl(
      )](o)), had no effect on halothane inhibition. Applications of K(+) channel
      blockers tetraethyl ammonium, 4-aminopyridine, Cs(+) or Ba(2+) either had no
      effect or augmented the inhibitory effect of halothane. On the other hand, the
      degree of inhibition by halothane was found to be dependent on [K(+)](o); the
      higher [K(+)](o), the larger the depression. In addition, decreases in [Na+]o and
      [Mg(2+)](o) reduced the excitation similar to that of halothane treatment, and
      the degree of halothane inhibition became larger with lower [Mg(2+)](o). These
      results lead to a hypothesis that halothane suppresses the excitation of
      presynaptic elements by inhibiting presynaptic Na(+) channels by shifting the
      steady-state inactivation curve in the hyperpolarizing direction.

PMID- 11994123
TI  - Adenosine depresses a Ca(2+)-independent step in transmitter exocytosis at frog
      motor nerve terminals.
AB  - The depressant action of adenosine on acetylcholine release at frog motor nerve
      terminals was studied by intracellular recording and Ca(2+)-imaging techniques.
      Adenosine (200 microm) quickly and reversibly decreased the amplitude and quantal
      content of end-plate potentials (EPPs) with no change in quantal size in a low
      Ca(2+), high-Mg(2+) solution, and EPP amplitude in normal Ringer containing d
      tubocurarine. Likewise, adenosine (200 microm) reduced miniature EPP (MEPP)
      frequency, but not amplitude, in a high-K(+) (6 mm) solution. Adenosine (40-200
      microm), however, did not affect single or repetitive impulse(s)-induced rises in
      Ca(2+) in the nerve terminals or its basal level. Adenosine (100-200 microm)
      reduced the Ca(2+)-independent enhancement of MEPP frequency caused by
      hypertonicity. EPPs induced by tetanic stimulation (33 Hz) in Ringer with d
      tubocurarine initially increased in amplitude within 10 stimuli and then declined
      to the minimum. Adenosine (200 microm) decreased EPP amplitude in the initial
      phase of the tetanus, but enhanced it in the middle phase, thus prolonging the
      decay of EPP amplitude. The total sum of these EPPs, reflecting the readily
      releasable pool of vesicles and its refilling, however, was not changed. The
      results suggest that adenosine inhibits a Ca(2+)-independent step of transmitter
      exocytosis at frog motor nerve terminals.

PMID- 11994124
TI  - Functional glycine receptors are expressed by postnatal nestin-positive neural
      stem/progenitor cells.
AB  - Multipotent neural stem and progenitor cells (NS/PCs) are well-established cell
      subpopulations occurring in the developing, and also in the mature mammalian
      nervous systems. Trophic and transcription factors are currently the main signals
      known to influence the development and the commitment of NS/PCs and their
      progeny. However, recent studies suggest that neurotransmitters could also
      contribute to neural development. In that respect, rodent-cultured embryonic
      NS/PCs have been reported to express functional neurotransmitter receptors. No
      similar investigation has, however, been made in postnatal and/or in adult rodent
      brain stem cells. In this study, using RT-PCR and immunocytochemical methods, we
      show that alpha(1)-, alpha(2)- and beta-subunit mRNAs and alpha-subunit proteins
      of the glycine ionotropic receptor are expressed by 80.5 +/- 0.9% of postnatal
      rat striatum-derived, nestin-positive cells within cultured neurospheres. Whole
      cell patch-clamp experiments further demonstrated that glycine triggers in 33.5%
      of these cells currents that can be reversibly blocked by strychnine and
      picrotoxin. This demonstrates that NS/PCs express functional glycine receptors,
      the consequence(s) of their activation remaining unknown.

PMID- 11994125
TI  - MOR-1-immunoreactive neurons in the dorsal horn of the rat spinal cord: evidence
      for nonsynaptic innervation by substance P-containing primary afferents and for
      selective activation by noxious thermal stimuli.
AB  - A direct action of mu-opioid agonists on neurons in the spinal dorsal horn is
      thought to contribute to opiate-induced analgesia. In this study we have
      investigated neurons that express the mu-opioid receptor MOR-1 in rat spinal cord
      to provide further evidence about their role in nociceptive processing. MOR-1
      immunoreactive cells were largely restricted to lamina II, where they comprised
      approximately 10% of the neuronal population. The cells received few contacts
      from nonpeptidergic unmyelinated afferents, but many from substance P-containing
      afferents. However, electron microscopy revealed that most of these contacts were
      not associated with synapses. None of the MOR-1 cells in lamina II expressed the
      neurokinin 1 receptor; however, the mu-selective opioid peptide endomorphin-2 was
      present in the majority (62-82%) of substance P axons that contacted them.
      Noxious thermal stimulation of the foot induced c-Fos expression in approximately
      15% of MOR-1 cells in the medial third of the ipsilateral dorsal horn at mid
      lumbar level. However, following pinching of the foot or intraplantar injection
      of formalin very few MOR-1 cells expressed c-Fos, and for intraplantar formalin
      injection this result was not altered significantly by pretreatment with systemic
      naloxone. Although these findings indicate that at least some of the neurons in
      lamina II with MOR-1 are activated by noxious thermal stimulation, the results do
      not support the hypothesis that the cells have a role in transmitting nociceptive
      information following acute mechanical or chemical noxious stimuli.

PMID- 11994126
TI  - Quantification and localization of PEGylated polycyanoacrylate nanoparticles in
      brain and spinal cord during experimental allergic encephalomyelitis in the rat.
AB  - Under healthy conditions, the blood-brain barrier (BBB) limits the passage of
      solutes and cells from the blood to the CNS. During neurological diseases, BBB
      permeability increases dramatically and it has been hypothesized that drug
      carrier systems such as polymeric nanoparticles could cross the BBB and penetrate
      into the CNS. PEGylated polyalkylcyanoacrylate nanoparticles (long-circulating
      carrier) are one such system and have been investigated during experimental
      allergic encephalomyelitis (EAE). Brain and spinal cord concentrations of [(14)C]
      radiolabelled PEGylated polyalkylcyanoacrylate nanoparticles were compared with
      another blood long-circulating carrier (poloxamine 908-coated
      polyalkylcyanoacrylate nanoparticles) and with conventional non-long-circulating
      polyalkylcyanoacrylate nanoparticles. The microscopic localization of fluorescent
      nanoparticles in the CNS was also investigated in order to further understand the
      mechanism by which the particles penetrate the BBB. The results demonstrate that
      the concentration of PEGylated nanoparticles in the CNS, especially in white
      matter, is greatly increased in comparison to conventional non-PEGylated
      nanoparticles. In addition, this increase was significantly higher in
      pathological situations where BBB permeability is augmented and/or macrophages
      have infiltrated. Passive diffusion and macrophage uptake in inflammatory lesions
      seems to be the mechanism underlying such particles' brain penetration. Based on
      their long-circulating properties in blood and on their surface characteristics
      that allow cell interactions, PEGylated nanoparticles penetrated into CNS to a
      larger extent than all the other formulations tested. Thus, PEGylated
      polycyanoacrylate nanoparticles are proposed here as a new brain delivery system
      for neuroinflammatory diseases.

PMID- 11994127
TI  - Focal application of neutralizing antibodies to soluble neurotrophic factors
      reduces collateral axonal branching after peripheral nerve lesion.
AB  - A major reason for the insufficient recovery of function after motor nerve injury
      are the numerous axonal branches which often re-innervate muscles with completely
      different functions. We hypothesized that a neutralization of diffusable
      neurotrophic factors at the lesion site in rats could reduce the branching of
      transected axons. Following analysis of local protein expression by
      immunocytochemistry and by in situ hybridization, we transected the facial nerve
      trunk of adult rats and inserted both ends into a silicon tube containing (i)
      collagen gel with neutralizing concentrations of antibodies to NGF, BDNF, bFGF,
      IGF-I, CNTF and GDNF; (ii) five-fold higher concentrations of the antibodies and
      (iii) combination of antibodies. Two months later, retrograde labelling was used
      to estimate the portion of motoneurons the axons of which had branched and
      projected into three major branches of the facial trunk. After control
      entubulation in collagen gel containing non-immune mouse IgG 85% of all
      motoneurons projecting along the zygomatic branch sprouted and sent at least one
      twin axon to the buccal and/or marginal-mandibular branches of the facial nerve.
      Neutralizing concentrations of anti-NGF, anti-BDNF and anti-IGF-I significantly
      reduced sprouting. The most pronounced effect was achieved after application of
      anti-BDNF, which reduced the portion of branched neurons to 18%. All effects
      after a single application of antibodies were concentration-dependent and
      superior to those observed after combined treatment. This first report on
      improved quality of reinnervation by antibody-therapy implies that, in rats, the
      post-transectional collateral axonal branching can be reduced without obvious
      harmful effects on neuronal survival and axonal elongation.

PMID- 11994128
TI  - Response properties of neurons in the core of the central nucleus of the inferior
      colliculus of the barn owl.
AB  - The central nucleus of the inferior colliculus (ICC) is particularly important
      for the processing of interaural time differences (ITDs). In the barn owl,
      neuronal best frequencies in a subnucleus of the ICC, the ICCcore, span the
      animal's entire hearing range (approximately equal to 200-10 000 Hz). This means
      that low-frequency ITD-sensitive ICCcore neurons in the owl can be directly
      compared to ITD-sensitive mammalian ICC neurons with similar best frequencies as
      well as to the high-frequency ITD-sensitive neurons usually studied in owls. This
      report represents a first attempt to systematically describe important
      physiological properties of ICCcore neurons in the barn owl, with particular
      attention to the low-frequency region (< 2 kHz). Responses were obtained from 133
      neurons or small clusters of neurons; recording sites were confirmed by
      histological reconstruction of electrode tracks based on electrolytic lesions.
      Iso-intensity frequency response functions were typically approximately equal to
      1 octave wide in the low-frequency range and approximately equal to 1/3 octave
      wide in the high-frequency range. Most neurons were ITD-tuned; both noise and
      pure tone stimuli yielded periodic ITD tuning curves with several equivalent
      response maxima. In most cases ITD tuning curves had a response peak within the
      barn owl's physiological ITD range. ITD tuning widths were inversely correlated
      with neuronal best frequency. None of the ICCcore neurons studied were sensitive
      to interaural level differences. Monaural inputs to ICCcore cells were typically
      binaurally balanced, i.e. they exhibited similar response thresholds, dynamic
      ranges, slopes and saturation levels, for both left and right ear monaural
      stimulation.

PMID- 11994129
TI  - Neuronal activity in the monkey motor thalamus during bicuculline-induced
      dystonia.
AB  - Recent data suggest that a decreased basal ganglia output may occur in dystonia,
      resulting in an increased thalamic drive to the mesial premotor cortex. In a
      previous work we found that injection of the GABAA antagonist bicuculline into
      the rostral motor thalamus induced contralateral dystonic postures, whereas
      myoclonic jerks were frequent after injection into the caudal motor thalamus. In
      the present study, we performed electrophysiological recordings in the rostral
      and caudal parts of the ventrolateral thalamus of two cynomolgus monkeys before
      and after bicuculline injections or saline injections. Discharge frequencies of
      thalamic neurons were increased after bicuculline injections vs. controls. Their
      discharge pattern was more bursty in the caudal part in which bursts of neuronal
      activity were correlated with myoclonic jerks. After bicuculline injection,
      neurons responded more frequently and less selectively to passive limb movements
      in both parts of the motor thalamus. Conversely, the response to microstimulation
      increased after bicuculline injection, particularly in the caudal part. Our data
      show that acute bicuculline-induced dystonia is associated with a reversible
      overactivity and disorganization of neuronal activity in the motor thalamus. Such
      a phenomenon might induce an overspreading of cortical activity leading to
      dystonia. We postulate that the distinct clinical syndromes observed after
      bicuculline injections into the rostral and caudal motor thalamus are due to
      differences both in the neuronal circuitry within each thalamic nucleus and in
      segregated cortical projections.

PMID- 11994130
TI  - Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine
      intravenous self-administration.
AB  - Conditioning theories propose that, through a Pavlovian associative process,
      discrete stimuli acquire the ability to elicit neural states involved in the
      maintenance and relapse of a drug-taking behaviour. Experimental evidence
      indicates that drug-related cues play a role in relapse, however, their influence
      on the development and maintenance of drug self-administration has been poorly
      investigated. In this report, we analysed the effects of a drug-associated cue
      light on acquisition, maintenance and reinstatement of intravenous cocaine self
      administration. The results show that a cocaine-associated cue light can act as
      an incentive in absence of the drug, but does not directly modify drug
      reinforcing effects. Contingent and non-contingent presentations of a cocaine
      associated cue light reinstated an extinguished self-administration behaviour.
      However, regardless of whether or not a cue light was associated with cocaine
      infusions, rats acquire cocaine intravenous self-administration reaching the same
      levels of intake. Furthermore, after self-administration has been acquired in
      presence of the cue light, the omission of the cue light or its non-contingent
      presentation did not modify rat behaviour. In conclusion, our work shows that
      cocaine-associated explicit cues do not directly interfere with the reinforcing
      effects of the drug.

PMID- 11994131
TI  - Neuronal populations in primary motor cortex encode bimanual arm movements.
AB  - Previous studies have shown that activity of neuronal populations in the primary
      motor cortex (MI), processed by the population vector method, faithfully predicts
      upcoming movements. In our previous studies we found that single neurons
      responded differently during movements of one arm vs. combined movements of the
      two arms. It was, therefore, not clear whether the population vector approach
      could produce reliable movement predictions also for bimanual movements. This
      study tests this question by comparing the predictive quality of population
      vectors for unimanual and bimanual arm movements. We designed a bimanual motor
      task that requires coordinated movements of the two arms, in which each arm may
      move in eight directions, and recorded single unit activity in the MI of two
      rhesus (Macaca mulatta) monkeys during the performance of unimanual and bimanual
      arm movements. We analysed the activity of 212 MI cells from both hemispheres and
      found that, despite bimanual related activity, the directional tuning and
      preferred directions of most cells were preserved in unimanual and bimanual
      movements. We demonstrate that population vectors, constructed from the activity
      of MI cells, predict accurately the direction of movement both for unimanual and
      for bimanual movements even when the two arms move simultaneously in different
      directions.

PMID- 11994132
TI  - Increased hypothalamic expression of prolactin in lactation: involvement in
      behavioural and neuroendocrine stress responses.
AB  - Prolactin (PRL) has recently been shown to exert an anxiolytic effect in male and
      virgin female rats, as well as an inhibitory tone on hypothalamic-pituitary
      adrenal (HPA) axis activity. Reduced emotional and neuroendocrine stress
      responses have been described in lactation, a time of high blood PRL levels. Here
      we tested brain PRL-receptor (PRL-R)-mediated effects on anxiety, maternal
      behaviour, HPA axis and oxytocin stress responses in lactating rats. Chronic
      intracerebroventricular (i.c.v.) infusion of antisense oligonucleotides against
      the long form of the PRL-R (AS; osmotic minipump, 0.5 microg/0.5 microL/h) in
      order to downregulate brain PRL-R expression increased the anxiety-related
      behaviour on the elevated plus maze (P < 0.01) compared with mixed bases- and
      vehicle-treated rats. Also, PRL-R AS treatment impaired maternal behaviour (P <
      0.05), whereas physiological parameters of lactation (weight gain of the litter,
      number of milk ejection reflexes during a 20-min suckling period) were not
      affected. PRL-R AS treatment further evoked an increase (P < 0.05) in the stress
      induced adrenocorticotropin release, demonstrating an inhibitory role of PRL on
      HPA axis responses in lactation. Inhibition of stress responses of the oxytocin
      system by brain PRL was evidenced by higher stress-induced (P < 0.05) plasma
      oxytocin concentration in PRL-R AS-treated lactating rats and, in contrast,
      decreased stress-induced oxytocin release (P < 0.01) in chronic i.c.v. ovine PRL
      treated (1 microg/0.5 microL/h) virgin rats. Finally, an increased expression of
      the hypothalamic PRL gene was seen by RT-PCR in pregnancy and lactation,
      suggesting an activated state of the brain PRL system during the peripartum
      period. In summary, activation of the brain PRL system in the peripartum period
      significantly contributes to emotional and neuroendocrine adaptations, including
      downregulation of the responsiveness of the HPA axis and oxytocin systems to
      stressors seen at this time.

PMID- 11994133
TI  - Protein kinase C-mediated translocation of secretory vesicles to plasma membrane
      and enhancement of neurotransmitter release from PC12 cells.
AB  - In order to elucidate the molecular mechanism of phorbol ester-induced
      potentiation of neurotransmitter release, changes in the subcellular distribution
      of secretory vesicles were studied in PC12 cells. Dopamine (DA) and acetylcholine
      containing vesicles were selectively labelled by expressing green fluorescent
      protein-conjugated vesicular monoamine transporter and vesicular acetylcholine
      transporter, respectively. In the resting state, these vesicles were distributed
      throughout the cytoplasm. Phorbol-12-myristate-13-acetate (PMA), but not the
      inactive analogue 4 alpha-PMA, induced a redistribution of both types of
      secretory vesicles near the plasma membrane, and this change was abolished by a
      protein kinase C (PKC) inhibitor, bisindolylmaleimide I (BIS). PMA also induced a
      marked enhancement of depolarization-induced DA release and phosphorylation of
      SNAP-25 at Ser187. BIS completely inhibited PMA-induced SNAP-25 phosphorylation
      but suppressed PMA-induced enhancement of DA release only partially. These
      results suggest that PMA enhances neurotransmitter release from PC12 cells by
      both PKC-dependent and PKC-independent mechanisms, and PKC enhances
      neurotransmitter release by recruiting secretory vesicles to the plasma membrane.

PMID- 11994134
TI  - Frontal theta activity in humans increases with memory load in a working memory
      task.
AB  - Recent theoretical work has suggested that brain oscillations in the theta band
      are involved in active maintenance and recall of working memory representations.
      To test this theoretical framework we recorded neuromagnetic responses from 10
      subjects performing the Sternberg task. Subjects were required to retain a list
      of 1, 3, 5 or 7 visually presented digits during a 3-s retention period. During
      the retention period we observed ongoing frontal theta activity in the 7-8.5-Hz
      band recorded by sensors over frontal brain areas. The activity in the theta band
      increased parametrically with the number of items retained in working memory. A
      time-frequency analysis revealed that the task-dependent theta was present during
      the retention period and during memory scanning. Following the memory task the
      theta activity was reduced. These results suggest that theta oscillations
      generated in frontal brain regions play an active role in memory maintenance.

PMID- 11994135
TI  - Projections from the parahippocampal region to the prefrontal cortex in the rat:
      evidence of multiple pathways.
AB  - The purpose of the present study was to investigate, by means of anterograde
      tracing methods, the detailed organization of the parahippocampal-prefrontal
      projections in the rat brain. Efferents from the perirhinal cortex were found to
      terminate principally in both the ventromedial (prelimbic and infralimbic
      cortices) and lateral (agranular insular cortex) regions of the prefrontal
      cortex. Terminal fields were observed mainly in the superficial layers of the
      prefrontal cortex. Projections arising from the dorsolateral entorhinal cortex,
      which borders the perirhinal cortex along its ventral extent, were similarly
      directed to the ventromedial and lateral prefrontal cortices but also encompassed
      other frontal areas (dorsomedial and orbital prefrontal regions). Terminal fields
      of entorhinal projections were also found in the superficial layers of the
      prefrontal cortex. A third pathway, taking its source in the post-rhinal cortex,
      presented striking topographical differences with the two other output systems.
      Hence, post-rhinal efferences terminated only in the ventrolateral orbital area.
      The results indicate that two main routes originate from the parahippocampal
      region to reach the prefrontal cortex. One pathway involves the rostral and
      lateral portions of the parahippocampal region (perirhinal and dorsolateral
      entorhinal cortices), and the other relies on its most caudal region, the post
      rhinal cortex. The presence of such different multiple parahippocampal-prefrontal
      pathways may have functional relevance for learning and memory processes.

PMID- 11994136
TI  - Cytokine therapy in dermatology.
AB  - Cytokines have been in the focus of scientific interest for some years now.
      Analysing their expression permitted a better understanding of the pathogenesis
      of various diseases, including in dermatology. Moreover, they are now far beyond
      the stage when they were of interest only to the pathophysiological research
      sector: some cytokine therapies are already being employed as part of the
      clinical practice. In fact, several cytokines are used for the treatment of
      malignant, inflammatory and infectious skin diseases. Their stage of development
      ranges from advanced, already approved and well established therapies (e.g. IFN
      alpha and IL-2 for melanoma) to early explorative trials (e.g. IL-4 and IL-10 for
      psoriasis). Some of the new approaches currently under investigation will
      actually lead to registration of new drugs for dermatological treatment and to
      supplement existing therapeutic options. Beside this, the results of clinical
      trials with cytokines are significantly contributing to our understanding of the
      pathophysiology of diseases. They will give a better insight into which
      mechanisms play a greater or lesser part in their development and may generate
      momentum for still better targeted pharmacological approaches. Here we would like
      to give an overview about the current stage of cytokine therapy and the prospects
      for dermatological indications. The terminology and immunobiology of cytokines
      are also briefly discussed, since for a sensible interpretation of the relevant
      findings a basic knowledge of these biologically highly active messenger
      substances is essential.

PMID- 11994137
TI  - Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome
      resulting from mutations in plakophilin 1.
AB  - We report a 42-year-old Japanese man with an unusual autosomal recessive
      genodermatosis. The clinical features comprised normal skin at birth, loss of
      scalp hair at 3-months of age after a febrile illness, progressive nail dystrophy
      during infancy, palmoplantar keratoderma starting around the age of 18 years and
      trauma-induced skin fragility and blisters noted from the age of 20 years. Skin
      biopsy of rubbed non-lesional skin revealed widening of spaces between adjacent
      keratinocytes from the suprabasal layer upwards. Electron microscopy demonstrated
      a reduced number of hypoplastic desmosomes. Immunohistochemical labeling showed a
      reduction in intercellular staining for the desmosome component plakophilin 1.
      Mutation analysis revealed a homozygous intron 11 donor splice site mutation in
      the plakophilin 1 gene, 2021+1 G>A (GenBank no. Z34974). RT-PCR, using RNA
      extracted from the skin biopsy, provided evidence for residual low levels of the
      full-length wild-type transcript (approximately 8%) as well as multiple other
      near full-length transcripts, one of which was in frame leading to deletion of 17
      amino acids from the 9th arm-repeat unit of the plakophilin 1 tail domain. Thus,
      the molecular findings help explain the clinical features in the patient, who has
      a similar but milder phenotype to previously reported patients with skin
      fragility-ectodermal dysplasia syndrome associated with complete ablation of
      plakophilin 1 (OMIM 604536). This new 'mitis' phenotype provides further
      clinicopathological evidence for the role of plakophilin 1 in keratinocyte cell
      cell adhesion and ectodermal development.

PMID- 11994138
TI  - Interspecies conservation and differential expression of mouse desmoglein gene
      family.
AB  - Epithelial cell adhesion is mediated by intercellular junctions, called
      desmosomes. Desmogleins (Dsg; Dsg1, Dsg2 and Dsg3) are calcium-dependent
      transmembrane adhesion components of the desmosomes. While Dsg1 and Dsg3 are
      mainly restricted to stratified squamous epithelia, Dsg2 is expressed in
      essentially all desmosome-containing epithelia. In the epidermis, Dsg2 and Dsg3
      are expressed in the basal keratinocytes while Dsg1 is expressed throughout the
      upper differentiating cell layers. To date, in mouse, only Dsg3 has been
      characterized by molecular cloning. In this study, we have cloned and
      characterized the mouse Dsg1 and Dsg2 genes. The full-length mouse Dsg1 cDNA (5.5
      kb) contains an open reading frame (ORF) of 3171 bp encoding a precursor protein
      of 1057 amino acids. The Dsg2 cDNA (6.3 kb) has an ORF of 3366 bp coding for a
      precursor protein of 1122 amino acids. Mouse Dsg2 protein shares 76% identity
      with human DSG2 but only 26% and 33% identity with mouse Dsg1 and Dsg3,
      respectively. Analysis of intron/exon organization of the desmoglein genes
      revealed significant conservation. However, the mRNA expression patterns of these
      desmogleins during mouse embryonic development and in various adult tissues are
      variable. While Dsg2 and Dsg3 are expressed in all developmental stages, Dsg1
      expression is delayed until day 15 of mouse embryos. In adult mouse tissues, Dsg2
      is widely expressed while the expression of Dsg1 and Dsg3 is restricted to select
      tissues. In summary, while desmogleins share high homology at both the gene and
      protein level, their expression is spatially and temporally regulated,
      potentially contributing to their significant role in cell-cell adhesion during
      development.

PMID- 11994139
TI  - Induction of skewed Th1/Th2 T-cell differentiation via subcutaneous immunization
      with Freund's adjuvant.
AB  - CD4+ T cells differentiate into at least two distinct subsets, Th1 and Th2, that
      are characterized by their cytokine-producing profiles. In this study, we
      attempted to delineate whether and how CD4+ T-cell responses could be skewed in
      one direction or another. BALB/c mice were immunized with chicken ovalbumin (OVA)
      emulsified with either incomplete or complete Freund's adjuvant (IFA or CFA).
      When lymph node cells were assessed on day 7, antigen specific proliferation was
      similarly observed both in the mice immunized with IFA and CFA. In contrast, on
      day 28 there was a less significant response in the mice primed with IFA than in
      those primed with CFA. ELISA analyses revealed more Th1 predominant cytokine
      production by T cells immunized with OVA+CFA rather than in IFA, which resulted
      in balanced IFN-gamma and IL-4 production. Flow cytometric analyses of
      intracellular cytokines confirmed that T cells from mice primed with CFA produced
      Th1 cytokines more predominantly. When lymph node dendritic cells (DC) were
      compared for their co-stimulatory molecule expression, priming with CFA and IFA
      similarly upregulated CD80 and CD86 expression by lymph node DC, and no
      significant differences were observed in CD40, 54, 80 and 86 expression between
      the DC harvested from IFA and CFA immunized mice. In addition, both priming with
      IFA and CFA similarly induced IL-12 production by DC. Thus, although the
      reason(s) for the preferential induction of a Th1/Th2 response remains unknown,
      these results indicate that a relatively Th1/Th2 skewed response is
      differentially induced by different types of adjuvants, and induction of a Th1
      skewed response may be responsible for long lasting cellular immunity.

PMID- 11994140
TI  - Expression of the C-C chemokine MIP-3 alpha/CCL20 in human epidermis with
      impaired permeability barrier function.
AB  - External assault to the skin is followed by an epidermal response including
      synthesis of DNA, lipids, cytokines and migration of antigen presenting cells.
      MIP-3 alpha (CCL20, LARC, Exodus-1, Scya20) is a recently described C-C
      chemokine, predominantly expressed in extralymphoid tissue, which is known to
      direct migration of dendritic cell precursors and memory lymphocytes to sites of
      antigen invasion. We assessed the expression of MIP-3 alpha in human skin using
      semi-quantitative polymerase chain reaction. In vivo, MIP-3 alpha mRNA was
      constitutively expressed at low levels in untreated human epidermis. After acute
      disruption of the epidermal permeability barrier MIP-3 alpha mRNA was upregulated
      in the epidermal fraction, whereas dermal MIP-3 alpha mRNA levels remained
      unchanged. In vitro, MIP-3 alpha was increased in cultured keratinocytes treated
      with IL-1 alpha and TNF-alpha and was present in immature and mature dendritic
      cells, THP-1 monocytic cells and activated T cells. Finally, skin biopsies from
      patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant
      expression. In biopsies from atopic dermatitis and graft vs. host disease a weak
      signal was present, whereas no expression was found in scleroderma and toxic
      epidermal necrolysis. We conclude that regulation of MIP-3 alpha mRNA is part of
      the epidermal response to external assault. Its upregulation may represent a
      danger signal for increased immunosurveillance in barrier disrupted skin and
      inflammatory skin conditions with impaired barrier function to counteract
      potential antigen invasion.

PMID- 11994141
TI  - Topical retinoic acid alters the expression of cellular retinoic acid-binding
      protein-I and cellular retinoic acid-binding protein-II in non-lesional but not
      lesional psoriatic skin.
AB  - Therapeutic retinoids have profound effects on psoriatic skin pathology but their
      interactions with various retinoid-binding proteins in lesional vs non-lesional
      skin have not been investigated. Using quantitative real-time PCR the mRNA
      expression of cellular retinol-binding protein I (CRBPI) and retinoic acid
      binding protein I/II (CRABPI/CRABPII) was studied in psoriatic and healthy
      control (=normal) skin after 4 days of occlusive RA/vehicle treatment (n=6).
      Untreated psoriatic lesions showed a markedly elevated CRABPII/CRABPI ratio,
      while the CRBPI level was reduced in lesional and non-lesional skin as compared
      to normal skin. In RA-treated normal and non-lesional skin, the mRNA expression
      of CRBPI was unaltered while that of CRABPI and CRABPII was reduced by
      approximately 80% and increased approximately 5-fold, respectively, as compared
      to vehicle-treated skin. In contrast, lesional skin exposed to RA showed an
      almost 90% increase in CRBPI transcripts but unaltered expression of CRABPI and
      CRABPII, yet, the mRNA expression of several inflammatory mediators, e.g.
      inducible nitric oxide synthase, interferon-gamma and interleukin-1beta, was
      clearly reduced. Immunohistochemistry localized CRABPII to suprabasal
      keratinocytes in normal skin and revealed markedly elevated levels in lesional
      skin. RA treatment induced CRABPII protein expression in normal and non-lesional
      skin, to similar levels as in untreated lesions. The results indicate that the
      effects of RA differ in normal/non-lesional psoriatic skin and lesional skin.
      Whether the high expression of CRABPII in psoriatic skin lesions is due to
      increased amounts of endogenous retinoids in lesional skin or reflects an
      abnormal regulation of the CRABPII gene in psoriasis remains to be studied.

PMID- 11994142
TI  - Improved detection of lacZ reporter gene expression in transgenic epithelia by
      immunofluorescence microscopy.
AB  - The bacterial lacZ gene is commonly used as a reporter for the in vivo analysis
      of gene regulation in transgenic mice. However, several laboratories have
      reported poor detection of beta-galactosidase (the lacZ gene product) using
      histochemical techniques, particularly in skin. Here we report the difficulties
      we encountered in assessing lacZ expression in transgenic keratinocytes using
      classic X-gal histochemical protocols in tissues shown to express the transgene
      by mRNA in situ hybridization. We found that lacZ reporter gene expression could
      be reliably detected in frozen tissue sections by immunofluorescence analysis
      using a beta-galactosidase-specific antibody. Moreover, we were able to localize
      both transgene and endogenous gene products simultaneously using double-label
      immunofluorescence. Our results suggest that antibody detection of beta
      galactosidase should be used to verify other assays of lacZ expression,
      particularly where low expression levels are suspected or patchy expression is
      observed.

PMID- 11994143
TI  - What is the 'true' function of skin?
AB  - Conventional textbook wisdom portrays the skin as an organ that literally enwraps
      whatever each of us stands for as a more or less functional, individual member of
      the mammalian species, and has it that the skin primarily establishes, controls
      and transmits contacts with the external world. In addition, the skin has long
      been recognized to protect the organism from deleterious environmental impacts
      (physical, chemical,microbiological), and is well-known as crucial for the
      maintenance of temperature, electrolyte and fluid balance. Now, ever more studies
      are being published that show the skin to also operate as a huge and highly
      active biofactory for the synthesis,processing and/or metabolism of an astounding
      range of e.g. structural proteins, glycans, lipids and signaling molecules.
      Increasingly, it becomes appreciated that the skin, furthermore, is an integral
      component of the immune, nervous and endocrine systems, with numerous lines of
      cross-talk between these systems established intracutaneously (e.g. Ann NY Acad
      Sci Vol 885, 1999; Endocrine Rev 21:457-487, 2000; Physiol Rev 80:980-1020, 2001;
      Exp Dermatol 10: 349-367, 2001). All these emerging cutaneous functions beyond
      the classical image of the skin as a barrier and sensory organ are immediately
      relevant for many of the quandaries that clinical dermatology, dermatopathology,
      and dermatopharmacology are still struggling with to-date, and offer the
      practising dermatologist attractive new targets for therapeutic intervention.
      Yet, many of these skin functions are not even mentioned in dermatology textbooks
      and await systematic therapeutic targeting. Following a suggestion by Enno
      Christophers, the current 'Controversies' feature brings together an unusually
      diverse council of biologists and clinicians, who share their thought-provoking
      views with the readers and allow us to peek into the future of research in
      cutaneous biology, not the least by reminding us of the -- often ignored --
      evolutionary and embryonal origins of our favorite organ. Hopefully, this unique
      discussion feature will foster an understanding of the 'true' skin functions that
      is both more comprehensive and more profound than conventional teaching on this
      topic, and will stimulate more than 'skin-deep' reflections on the full range of
      skin functions.

PMID- 11994144
TI  - Regulation of autolysins in teichuronic acid-containing Bacillus subtilis cells.
AB  - Bacillus subtilis cells grown under phosphate starvation induce teichuronic acid
      (TUA) synthesis while simultaneously repressing teichoic acid synthesis (TA). The
      turnover rates of TA-containing and TUA-containing walls are similar, indicating
      that autolysin function is similar and suggesting that modulation of autolytic
      function may be similar. In this study, it is demonstrated, utilizing fluorescein
      isothiocyanate (FITC)-dextran to probe the wall pH, that a low pH exists in the
      wall matrix. A second probe, cationized ferritin (CF), was used to observe cell
      surface protonation. Suspensions of B. subtilis cells containing either TA or TUA
      were aggregated with CF only after the addition of a proton-motive-force
      dissipating agent. Respiring B. subtilis TUA-containing cells labelled with FITC
      dextran exhibited little fluorescence. Conversely, fluorescence intensities
      exhibited by cells de-energized with nitrogen gas were significantly greater. The
      effects of protonmotive force on autolytic activity were studied by adding cell
      wall protein extract containing concentrated autolysin to exponentially growing
      TA-containing and TUA-containing B. subtilis cells. Both TUA-containing and TA
      containing cells were lysed only after the addition of sodium azide. These data
      suggest that during normal growth the wall of TUA-containing B. subtilis cells is
      protonated, and proton-motive force influences autolytic regulation in both TUA
      containing and TA-containing B. subtilis cells.

PMID- 11994145
TI  - Sin recombinase from Staphylococcus aureus: synaptic complex architecture and
      transposon targeting.
AB  - The Sin recombinase from Staphylococcus aureus builds a distinctive DNA-protein
      synaptic complex to regulate strand exchange. Sin binds at two sites within an 86
      basepair (bp) recombination site, resH. We propose that inverted motifs at the
      crossover site, and tandem motifs at the regulatory site, are recognized by
      structurally disparate Sin dimers. An essential architectural protein, Hbsu,
      binds at a discrete central site in resH. Positions of Hbsu-induced DNA
      deformation coincide with natural targets for Tn552 integration. Remarkably, Sin
      has the same topological selectivity as Tn3 and gammadelta resolvases. Our model
      for the recombination synapse has at its core an assembly of four Sin dimers;
      Hbsu plays an architectural role that is taken by two resolvase dimers in models
      of the Tn3/gammadelta synapse.

PMID- 11994146
TI  - A basic helix-loop-helix protein with similarity to the fungal morphological
      regulators, Phd1p, Efg1p and StuA, controls conidiation but not dimorphic growth
      in Penicillium marneffei.
AB  - Members of the APSES protein group are basic helix-loop-helix (bHLH) proteins
      that regulate processes such as mating, asexual sporulation and dimorphic growth
      in fungi. Penicillium marneffei is a human pathogen and is the only member of its
      genus to display a dimorphic growth transition. At 25 degrees C, P. marneffei
      grows with a filamentous morphology and produces asexual spores from
      multicellular con-idiophores. At 37 degrees C, the filamentous morphology is
      replaced by yeast cells that reproduce by fission. We have cloned and
      characterized an APSES protein-encoding gene from P. marneffei that has a high
      degree of similarity to Aspergillus nidulans stuA. Deletion of stuA in P.
      marneffei showed that it is required for metula and phialide formation during
      conidiation but is not required for dimorphic growth. This suggests that APSES
      proteins may control processes that require budding (formation of the metulae and
      phialides, pseudohyphal growth in Saccharomyces cerevisiae and dimorphic growth
      in Candida albicans) but not those that require fission (dimorphic growth in P.
      marneffei). The A. nidulans DeltastuA mutant has defects in both conidiation and
      mating. The P. marneffei stuA gene was capable of complementing the conidiation
      defect but could only inefficiently complement the sexual defects of the A.
      nidulans mutant. This suggests that the P. marneffei gene, which comes from an
      asexual species, has diverged significantly from the A. nidulans gene with
      respect to sexual but not asexual development.

PMID- 11994147
TI  - ClpP-dependent degradation of PopR allows tightly regulated expression of the
      clpP3 clpP4 operon in Streptomyces lividans.
AB  - Five clpP genes have been identified in Streptomyces coelicolor. The clpP1 and
      clpP2 genes form one operon, the clpP3 and clpP4 genes form another, and clpP5 is
      monocistronic. Previous studies in Streptomyces lividans have shown that the
      first operon (clpP1 clpP2) is required for a normal cell cycle. Expression of the
      second operon (clpP3 clpP4) is activated by PopR if the first operon is
      nonfunctional. We show here that PopR degradation is primarily dependent on ClpP1
      and ClpP2, but can also be achieved by ClpP3 and ClpP4. The carboxy-terminus of
      PopR plays an essential part in the degradation process. Indeed, replacement of
      the last two alanine residues by aspartate residues greatly increased PopR
      stability. These substitutions did not impair PopR activity and, as expected,
      accumulation of the mutant form of PopR led to very strong expression of the
      clpP3 clpP4 operon. Increased PopR levels led to delayed sporulation. The results
      obtained in this study support the notion of cross-processing between ClpP1 and
      ClpP2.

PMID- 11994148
TI  - Complementary activities of SseJ and SifA regulate dynamics of the Salmonella
      typhimurium vacuolar membrane.
AB  - The Salmonella pathogenicity island 2 (SPI-2) type III secretion system (TTSS) of
      Salmonella typhimurium is required for bacterial replication within host cells.
      It acts by translocating effector proteins across the membrane of the Salmonella
      containing vacuole (SCV). The SifA effector is required to maintain the integrity
      of the SCV membrane, and for the formation in epithelial cells of Salmonella
      induced filaments (Sifs), which are tubular extensions of SCVs. We have
      investigated the role in S. typhimurium virulence of the putative SPI-2 effector
      genes sifB, srfJ, sseJ and sseI. An S. typhimurium strain carrying a mutation in
      sseJ was mildly attenuated for systemic virulence in mice, but strains carrying
      mutations in either srfJ, sseI or sifB had very little or no detectable virulence
      defect after intraperitoneal inoculation. Expression of SseJ in HeLa cells
      resulted in the formation of globular membranous compartments (GMCs), the
      composition of which appears to be similar to that of SCV membranes and Sifs. The
      formation of GMCs was dependent on the serine residue of the predicted
      acyltransferase/lipase active site of SseJ. Transiently expressed SseJ also
      inhibited Sif formation by wild-type bacteria, and was found to associate with
      Sifs, SCV membranes and simultaneously expressed SifA. Intracellular vacuoles
      containing sseJ mutant bacteria appeared normal but, in contrast to a sifA
      mutant, a sifA sseJ double mutant strain did not lose its vacuolar membrane,
      indicating that loss of vacuolar membrane around sifA mutant bacteria requires
      the action of SseJ. Collectively, these results suggest that the combined action
      of SseJ and SifA regulate dynamics of the SCV membrane in infected cells.

PMID- 11994149
TI  - The Bacillus subtilis cell division proteins FtsL and DivIC are intrinsically
      unstable and do not interact with one another in the absence of other septasomal
      components.
AB  - The bacterial septum appears to comprise a macromolecular assembly of essential
      cell division proteins (the 'septasome') that are responsible for physically
      dividing the cell during cytokinesis. FtsL and DivIC are essential components of
      this division machinery in Bacillus subtilis. We used yeast two-hybrid analysis
      as well as a variety of biochemical and biophysical methods to examine the
      proposed interaction between Bacillus subtilis FtsL and DivIC. We show that FtsL
      and DivIC are thermodynamically unstable proteins that are likely to be unfolded
      and therefore targeted for degradation unless stabilized by interactions with
      other components of the septasome. However, we show that this stabilization does
      not result from a direct interaction between FtsL and DivIC. We propose that the
      observed interdependence of DivIC and FtsL stability is a result of indirect
      interactions that are mediated by other septasomal proteins.

PMID- 11994150
TI  - Charting and unzipping the surface layer of Corynebacterium glutamicum with the
      atomic force microscope.
AB  - Bacterial surface layers (S-layers) are extracellular protein networks that act
      as molecular sieves and protect a large variety of archaea and bacteria from
      hostile environments. Atomic force microscopy (AFM) was used to asses the S-layer
      of Coryne-bacterium glutamicum formed of PS2 proteins that assemble into
      hexameric complexes within a hexagonal lattice. Native and trypsin-treated S
      layers were studied. Using the AFM stylus as a nanodissector, native arrays that
      adsorbed to mica as double layers were separated. All surfaces of native and
      protease-digested S-layers were imaged at better than 1 nm lateral resolution.
      Difference maps of the topographies of native and proteolysed samples revealed
      the location of the cleaved C-terminal fragment and the sidedness of the S-layer.
      Because the corrugation depths determined from images of both sides span the
      total thickness of the S-layer, a three-dimensional reconstruction of the S-layer
      could be calculated. Lattice defects visualized at 1 nm resolution revealed the
      molecular boundaries of PS2 proteins. The combination of AFM imaging and single
      molecule force spectroscopy allowed the mechanical properties of the
      Corynebacterium glutamicum S-layer to be examined. The results provide a basis
      for understanding the amazing stability of this protective bacterial surface
      coat.

PMID- 11994151
TI  - The Tol/Pal system function requires an interaction between the C-terminal domain
      of TolA and the N-terminal domain of TolB.
AB  - The Tol/Pal system of Escherichia coli is composed of the YbgC, TolQ, TolA, TolR,
      TolB, Pal and YbgF proteins. It is involved in maintaining the integrity of the
      outer membrane, and is required for the uptake of group A colicins and DNA of
      filamentous bacteriophages. To identify new interactions between the components
      of the Tol/Pal system and gain insight into the mechanism of colicin import, we
      performed a yeast two-hybrid screen using the different components of the Tol/Pal
      system and colicin A. Using this system, we confirmed the already known
      interactions and identified several new interactions. TolB dimerizes and the
      periplasmic domain of TolA interacts with YbgF and TolB. Our results indicate
      that the central domain of TolA (TolAII) is sufficient to interact with YbgF,
      that the C-terminal domain of TolA (TolAIII) is sufficient to interact with TolB,
      and that the amino terminal domain of TolB (D1) is sufficient to bind TolAIII.
      The TolA/TolB interaction was confirmed by cross-linking experiments on purified
      proteins. Moreover, we show that the interaction between TolA and TolB is
      required for the uptake of colicin A and for the membrane integrity. These
      results demonstrate that the TolA/TolB interaction allows the formation of a
      trans-envelope complex that brings the inner and outer membranes in close
      proximity.

PMID- 11994152
TI  - A NarX-Tar chimera mediates repellent chemotaxis to nitrate and nitrite.
AB  - Membrane receptors communicate between the external world and the cell interior.
      In bacteria, these receptors include the transmembrane sensor kinases, which
      control gene expression via their cognate response regulators, and
      chemoreceptors, which control the direction of flagellar rotation via the CheA
      kinase and CheY response regulator. Here, we show that a chimeric protein that
      joins the ligand-binding, transmembrane and linker domains of the NarX sensor
      kinase to the signalling and adaptation domains of the Tar chemoreceptor of
      Escherichia coli mediates repellent responses to nitrate and nitrite. Nitrate
      induces a stronger response than nitrite and is effective at lower
      concentrations, mirroring the relative sensitivity to these ligands exhibited by
      NarX itself. We conclude that the NarX-Tar hybrid functions as a bona fide
      chemoreceptor whose activity can be predicted from its component parts. This
      observation implies that ligand-dependent activation of a sensor kinase and
      repellent-initiated activation of receptor-coupled CheA kinase involve a similar
      transmembrane signal.

PMID- 11994153
TI  - Genetic analysis of tachyzoite to bradyzoite differentiation mutants in
      Toxoplasma gondii reveals a hierarchy of gene induction.
AB  - Developmental switching in Toxoplasma gondii, from the virulent tachyzoite to the
      relatively quiescent bradyzoite stage, is responsible for disease propagation and
      reactivation. We have generated tachyzoite to bradyzoite differentiation (Tbd-)
      mutants in T. gondii and used these in combination with a cDNA microarray to
      identify developmental pathways in bradyzoite formation. Four independently
      generated Tbd- mutants were analysed and had defects in bradyzoite development in
      response to multiple bradyzoite-inducing conditions, a stable phenotype after in
      vivo passages and a markedly reduced brain cyst burden in a murine model of
      chronic infection. Transcriptional profiles of mutant and wild-type parasites,
      growing under bradyzoite conditions, revealed a hierarchy of developmentally
      regulated genes, including many bradyzoite-induced genes whose transcripts were
      reduced in all mutants. A set of non-developmentally regulated genes whose
      transcripts were less abundant in Tbd- mutants were also identified. These may
      represent genes that mediate downstream effects and/or whose expression is
      dependent on the same transcription factors as the bradyzoite-induced set. Using
      these data, we have generated a model of transcription regulation during
      bradyzoite development in T. gondii. Our approach shows the utility of this
      system as a model to study developmental biology in single-celled eukaryotes
      including protozoa and fungi.

PMID- 11994154
TI  - Identification and characterization of differentiation mutants in the protozoan
      parasite Toxoplasma gondii.
AB  - Two forms of the protozoan parasite Toxoplasma gondii are associated with
      intermediate hosts such as humans: rapidly growing tachyzoites are responsible
      for acute illness, whereas slowly dividing encysted bradyzoites can remain latent
      within the tissues for the life of the host. In order to identify genetic factors
      associated with parasite differentiation, we have used a strong bradyzoite
      specific promoter (identified by promoter trapping) to drive the expression of T.
      gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) in stable
      transgenic parasites, providing a stage-specific positive/negative selectable
      marker. Insertional mutagenesis has been carried out on this parental line,
      followed by bradyzoite induction in vitro and selection in 6-thioxanthine to
      identify misregulation mutants. Two different mutants fail to induce the HXGPRT
      gene efficiently during bradyzoite differentiation. These mutants are also
      defective in other aspects of differentiation: they replicate well under
      bradyzoite growth conditions, lysing the host cell monolayer as effectively as
      tachyzoites. Expression of the major bradyzoite antigen BAG1 is reduced, and
      staining with Dolichos biflorus lectin shows reduced cyst wall formation.
      Microarray hybridizations show that these mutants behave more like tachyzoites at
      a global level, even under bradyzoite differentiation conditions.

PMID- 11994156
TI  - Two kinds of archaeal group II chaperonin subunits with different thermostability
      in Thermococcus strain KS-1.
AB  - The thermostability of the recombinant alpha- and beta-subunit homo-oligomers
      (alpha16mer and beta16mer) and of natural chaperonins purified from cultured
      Thermococcus strain KS-1 cells was measured to understand the mechanism for the
      thermal acclimatization of T. KS-1. The beta-subunit content of the natural
      chaperonin from cells grown at 90 degrees C was higher than that at 80 degrees C.
      The optimum temperature for ATPase activity of the natural chaperonins was 80-90
      degrees C, whereas that for alpha16mer and beta16mer was 60 degrees C and over 90
      degrees C respectively. Judging from the ATPase activity, beta16mer was more
      thermostable than alpha16mer. The thermostabilities of the natural chaperonins
      were intermediate between alpha16mer and beta16mer, whereas the natural
      chaperonin with a higher beta-subunit content was more stable than that with a
      lower beta-subunit content. Native polyacrylamide gel electrophoresis (PAGE)
      revealed that the chaperonin oligomers thermally dissociated to their ATPase
      inactive monomers. The thermal denaturation process monitored by circular
      dichroism showed that the free beta-subunit was more stable than the free alpha
      subunit, and that the secondary structure of the chaperonin monomer in the
      oligomer was more stable than that in the free monomer. These results suggest
      that the structure of these subunits was stabilized in the oligomer, and that an
      increase in the beta-subunit content conferred higher thermostability to the
      natural hetero-oligomeric chaperonin.

PMID- 11994155
TI  - Expression, mutagenesis and kinetic analysis of recombinant K1E endosialidase to
      define the site of proteolytic processing and requirements for catalysis.
AB  - Catalytically active, recombinant fusion proteins of bacteriophage E
      endosialidase were expressed and purified from Escherichia coli. Constructs with
      different fusion partners added to the amino terminus of the endosialidase were
      enzymatically active. A post-translational proteolytic cleavage was shown to
      occur between serine 706 and aspartate 707 to generate the 76 kDa mature enzyme
      from the 90 kDa translation product. Endosialidase truncated at the C-terminus
      from aspartate 707 was observed to have the same 76 kDa molecular weight as wild
      type enzyme using denaturing SDS-PAGE but, under native PAGE conditions, was not
      observed to form the approximately 250 kDa trimeric wild-type enzyme, implying
      that the C-terminus of the enzyme may be required for correct assembly of active
      trimer, rather than as part of the active site as has been previously suggested.
      Mutagenesis of aspartate 138 to alanine greatly reduced enzyme activity whereas
      conversion of other selected aspartate residues to alanine had less effect,
      consistent with similarities between the structure and cata-lytic mechanism of
      bacteriophage E endosialidase and those of exosialidases.

PMID- 11994157
TI  - Parallel pathways for oxidation of 14-membered polyketide macrolactones in
      Saccharopolyspora erythraea.
AB  - The glycosyltransferases OleG1 and OleG2 and the cytochrome P450 oxidase OleP
      from the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus have
      been expressed, either separately or from artificial gene cassettes, in strains
      of Saccharopolyspora erythraea blocked in erythromycin biosynthesis, to
      investigate their potential for the production of diverse novel macrolides from
      erythronolide precursors. OleP was found to oxidize 6-deoxyerythronolide B, but
      not erythronolide B. However, OleP did oxidize derivatives of erythronolide B in
      which a neutral sugar is attached at C-3. The oxidized products 3-O-mycarosyl-8a
      hydroxyerythronolide B, 3-O-mycarosyl-8,8a-epoxyerythronolide B, 6-deoxy-8
      hydroxyerythronolide B and the olefin 6-deoxy-8,8a-dehydroerythronolide B were
      all isolated and their structures determined. When oleP and the
      mycarosyltransferase eryBV were co-expressed in a gene cassette, 3-O-mycarosyl-6
      deoxy-8,8a-dihydroxyerythronolide B was directly obtained. When oleG2 was co
      expressed in a gene cassette together with oleP, 6-deoxyerythronolide B was
      converted into a mixture of 3-O-rhamnosyl-6-deoxy-8,8a-dehydroerythronolide B and
      3-O-rhamnosyl-6-deoxy-8,8a-dihydroxyerythronolide B, confirming previous reports
      that OleG2 can transfer rhamnose, and confirming that oxidation by OleP and
      attachment of the neutral sugar to the aglycone can occur in either order.
      Similarly, four different 3-O-mycarosylerythronolides were found to be substrates
      for the desosaminyltransferase OleG1. These results provide additional insight
      into the nature of the intermediates in OleP-mediated oxidation, and suggest that
      oleandomycin biosynthesis might follow parallel pathways in which epoxidation
      either precedes or follows attachment of the neutral sugar.

PMID- 11994158
TI  - Primosome assembly requirement for replication restart in the Escherichia coli
      holDG10 replication mutant.
AB  - In this report, we study the role of pre-primosome proteins in a strain in which
      the frequency of replication arrest is increased because of a mutation in a
      replication protein. The holDG10 mutant was used, in which replication restart
      involves replication fork reversal. As expected, PriA primosome assembly function
      is essential for growth of the holDG10 mutant. The priA300 mutation, which
      inactivates only the helicase function of PriA in vitro, and priB inactivation
      strongly impair viability. In contrast, priC inactivation has no effect.
      Therefore, PriB is more important than PriC for PriA-dependent replication fork
      restart in vivo. The gain of function mutation dnaC809 restores the viability of
      holDG10 priA and holDG10 priB mutants only to some extent. The dnaC809 820 double
      mutation restores full viability to the holDG10 mutant lacking either PriA or
      PriB. Similarly to the holDG10 single mutant, the holDG10 priA dnaC809 820 strain
      is depend-ent on RecBC for viability, indicating that facilitating primosome
      assembly using the dnaC809 820 mutation does not allow bypass of replication fork
      reversal.

PMID- 11994159
TI  - The repressor for an organic peroxide-inducible operon is uniquely regulated at
      multiple levels.
AB  - ohrR encodes a novel organic peroxide-inducible transcription repressor, and we
      have demonstrated that ohrR is regulated at the transcriptional and the post
      transcriptional levels. Primer extension results show that ohrR transcription
      initiates at the A residue of the ATG translation initiation codon for the ohrR
      coding sequence. Thus, the gene has a leaderless mRNA. The ohrR promoter (P1) has
      high homology to the consensus sequence for Xanthomonas promoters, which is
      reflected in the high in vivo promoter activity of P1. Deletion of a 139 bp
      fragment containing the P1 promoter showed that the sequences upstream of -35
      regions were required for neither the promoter activity nor OhrR autoregulation.
      In vitro, purified OhrR specifically binds to the P1 promoter. DNase I
      footprinting of OhrR binding to the P1 revealed a 44 bp region of protection on
      both DNA strands. The protected regions include the -35 and -10 regions of P1. We
      suggest that OhrR represses gene expression by blocking RNA polymerase binding to
      the promoter. There are two steps in the post-transcriptional regulation of ohrR,
      namely differential stability and inefficient translation of the mRNA. The
      bicistronic ohrR-ohr mRNA was highly labile and underwent rapid processing in
      vivo to give only stable monocistronic ohr mRNA and undetectable ohrR mRNA.
      Furthermore, the ohrR mRNA was inefficiently translated. We propose that, in
      uninduced cells, the concentration of OhrR is maintained at low levels by the
      autoregulation mechanism at the transcriptional levels and by the ohrR mRNA
      instability coupled with inefficient translation at the post-transcriptional
      level. Upon exposure to an organic peroxide, the compound probably interacts with
      OhrR and prevents it from repressing the P1 promoter, thus allowing high-level
      expression of the ohrR-ohr operon. The rapid processing of bicistronic mRNA gives
      highly stable ohr mRNA and corresponding high levels of Ohr, which remove an
      organic per-oxide. Once the peroxide has been removed, the autoregulation
      mechanism feeds back to inhibit the expression of the operon.

PMID- 11994160
TI  - Identification and characterization of genes encoding sex pheromone cAM373
      activity in Enterococcus faecalis and Staphylococcus aureus.
AB  - The sex pheromone cAM373 of Enterococcus faecalis and the related staph-cAM373 of
      Staphylococcus aureus were found to correspond to heptapeptides located within
      the C-termini of the signal sequences of putative prelipoproteins. The deduced
      mature forms of the lipoproteins share no detectable homology and presumably
      serve unrelated functions in the cells. The chromosomally encoded genetic
      determinants for production of the pheromones have been identified and designated
      camE (encoding cAM373) and camS (encoding staph-cAM373). Truncated and full
      length clones of camE were generated in Escherichia coli, in which cAM373
      activity was expressed. In E. faecalis, insertional inactivation in the middle of
      camE had no detectable phenotypic effects on the pheromone system. Establishment
      of an in frame translation stop codon within the signal sequence resulted in
      reduction of cAM373 activity to 3% of normal levels. The camS determinant has
      homologues in Staphylococcus epidermidis, Bacillus subtilis and Listeria
      monocytogenes; however, corresponding heptapeptides present within those
      sequences do not resemble staph-cAM373 closely. The particular significance of
      staph-cAM373 as a potential intergeneric inducer of transfer-proficient genetic
      elements is discussed.

PMID- 11994161
TI  - Pyruvate kinase from Chlamydia trachomatis is activated by fructose-2,6
      bisphosphate.
AB  - Pyruvate kinase is the final regulatory point in the catabolic Embden-Meyerhoff
      Parnas pathway, which controls the carbon flux of glycolytic intermediates and
      regulates the level of ATP in the cell. In a previous study, we identified,
      cloned and sequenced pyruvate kinase from the obligate intracellular bacterium
      Chlamydia trachomatis and demonstrated that the enzyme was active in crude
      extract. Here, we report the kinetic properties of highly purified C. trachomatis
      pyruvate kinase. The results indicate that C. trachomatis pyruvate kinase is 53.5
      kDa with a pH optima of 7.3. Kinetic studies show that C. trachomatis pyruvate
      kinase requires both K+ and Mg2+ ions for activity, exhibits sigmoidal kinetics
      with respect to phosphoenolpyruvate and Michaelis-Menten kinetics with respect to
      ADP. In addition, C. trachomatis pyruvate kinase is able to use alternative
      nucleoside diphosphates as phosphate acceptors, although it shows the greatest
      activity with ADP. In contrast to other bacterial pyruvate kinases that are
      activated by AMP, our data show that AMP, in addition to ATP and GTP, inhibits C.
      trachomatis pyruvate kinase. Surprisingly, unlike any other known bacterial
      pyruvate kinase, C. trachomatis pyruvate kinase was allosterically activated by
      fructose-2,6-bisphosphate, an important regulatory metabolite that has only been
      reported in eukaryotes.

PMID- 11994162
TI  - Regulation of yeast protein kinase C activity by interaction with the small
      GTPase Rho1p through its amino-terminal HR1 domain.
AB  - Protein kinase C from Saccharomyces cerevisiae (Pkc1p) constitutes a prototypic
      member of the protein kinase C superfamily, as it shares all the conserved
      regions scattered among the isoenzymes of higher eukaryotes. The functional
      significance of some of the conserved domains in the yeast enzyme has not yet
      been investigated. We examined strains carrying a partial deletion in the amino
      terminal region of the enzyme, which is homologous to the HR1 of the protein
      kinase C-related kinases. This strain was sensitive to the presence of caffeine,
      Calcofluor white and Congo red, all drugs known to affect mutants defective in
      the signal transduction pathway ensuring cellular integrity in which Pkc1p is a
      central component. Isolation of a single point mutation in HR1A, which shares the
      sensitivity to the drugs mentioned, confirmed the importance of this region for
      proper regulation of protein kinase C activity in vivo. Two-hybrid analysis
      provided evidence for an interaction of the small GTPase Rho1p with the HR1A
      region, in addition to the reported interaction of this protein with the C1
      region of Pkc1p. MAP kinase phosphorylation assays indicate that this Rho1p
      Pkc1p/HR1A interaction does not result in an activation of the kinase cascade.
      The intragenic lethality of mutants affected in both HR1A and the C1 domain
      reported in this work implies an essential role for Rho1p-Pkc1p interaction in
      yeast.

PMID- 11994163
TI  - Complete glycosylphosphatidylinositol anchors are required in Candida albicans
      for full morphogenesis, virulence and resistance to macrophages.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are involved in cell wall
      integrity and cell-cell interactions. We disrupted the Candida albicans homologue
      of the Saccharomyces cerevisiae GPI7/LAS21 gene, which encodes a GPI anchor
      modifying activity. In the mutant and on solid media, the yeast-to-hyphae
      transition was blocked, whereas chlamydospore formation was enhanced. However,
      the morphogenetic switch was normal in liquid medium. Abnormal budding patterns,
      cytokinesis and cell shape were observed in both liquid and solid media. The cell
      wall structure was also modified in the mutants, as shown by hypersensitivity to
      Calcofluor white. In vitro and in vivo assays revealed that the mutant interacted
      with its host in a modified way, resulting in reduced virulence in mice and
      reduced survival in the gastrointestinal environment of mice. The mitogen
      activated protein (MAP) kinase pathway of macrophages was downregulated by the
      wild-type cells but not by the DeltaCagpi7 null strains. In agreement with this
      abnormal behaviour, mutant cells were more sensitive to the lytic action of
      macrophages. Our results indicate that a functional GPI anchor is required for
      full hyphal formation in C. albicans, and that perturbation of the GPI
      biosynthesis results in hypersensitivity to host defences.

PMID- 11994164
TI  - The novel protein phosphatase PphA from Synechocystis PCC 6803 controls
      dephosphorylation of the signalling protein PII.
AB  - The family of PII signal transduction proteins consists of one of the most highly
      conserved signalling proteins in nature. The cyanobacterial PII homologue
      transmits signals on the nitrogen and carbon status of the cells through
      phosphorylation of a seryl residue. Recently, we identified a protein phosphatase
      2C (PP2C) homologue from the cyanobacterium Synechocystis PCC 6803, termed PphA,
      to be the cellular phospho-PII (PII-P) phosphatase. In this investigation, we
      characterized the enzymatic properties of PphA and investigated the regulation of
      its catalytic activity towards PII-P. PphA dephosphorylates phosphocasein and PII
      P with similar efficiency in a strictly Mg2+- or Mn2+-dependent reaction. Low
      molecular-weight phosphorylated molecules are poor substrates for PphA. Its
      reactivity towards PII-P, but not towards phosphocasein, is inhibited by various
      nucleotides, suggesting that this effect is based on specific properties of the
      PII protein. The inhibitory effect of ATP can be strongly enhanced by the
      addition of 2-oxoglutarate or oxaloacetate. At low concentrations of 2
      oxoglutarate, changes in the ATP levels within the physiological range affect the
      degree of PII-Pase inhibition, whereas at 2-oxoglutarate levels beyond 0.1 mM,
      inhibition is almost complete at very low ATP levels. This suggests that PII
      dephosphorylation is not only sensitive to 2-oxoglutarate and oxaloacetate
      levels, it also integrates signals from the energy charge of the cells under
      specific cellular conditions.

PMID- 11994165
TI  - KTI11 and KTI13, Saccharomyces cerevisiae genes controlling sensitivity to G1
      arrest induced by Kluyveromyces lactis zymocin.
AB  - The Kluyveromyces lactis zymocin and its gamma-toxin subunit inhibit cell cycle
      progression of Saccharomyces cerevisiae. To identify S. cerevisiae genes
      conferring zymocin sensitivity, we complemented the unclassified zymocin
      resistant kti11 and kti13 mutations using a single-copy yeast library. Thus, we
      identified yeast open reading frames (ORFs) YBL071w-A and YAL020c/ATS1 as KTI11
      and KTI13 respectively. Disruption of KTI11 and KTI13 results in the complex tot
      phenotype observed for the gamma-toxin target site mutants, tot1-7, and includes
      zymocin resistance, thermosensitivity, hypersensitivity to drugs and slow growth.
      Both loci, KTI11 and KTI13, are actively transcribed protein-encoding genes as
      determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and in
      vivo HA epitope tagging. Kti11p is highly conserved from yeast to man, and
      Kti13p/Ats1p is related to yeast Prp20p and mammalian RCC1, components of the Ran
      GTP/GDP cycle. Combining disruptions in KTI11 or KTI13 with a deletion in
      TOT3/ELP3 coding for the RNA polymerase II (RNAPII) Elongator histone
      acetyltransferase (HAT) yielded synthetic effects on slow growth phenotype
      expression. This suggests genetic interaction and possibly links KTI11 and KTI13
      to Elongator function.

PMID- 11994166
TI  - A hypermutator phenotype attenuates the virulence of Listeria monocytogenes in a
      mouse model.
AB  - The integrity of the genetic material of bacteria is guaranteed by a set of
      distinct repair mechanisms. The participation of these repair systems in
      bacterial pathogenicity has been addressed only recently. Here, we study for the
      first time the participation in virulence of the MutSL mismatch repair system of
      Listeria monocytogenes. The mutS and mutL genes, which are contiguous in the L.
      monocytogenes chromosome, were identified after in silico analysis. The deduced
      MutS shares 62% identity with MutS of Bacillus subtilis and 50% identity with
      HexA, its homologue in Streptococcus pneumoniae; MutL shares 59% identity with
      MutL of B. subtilis and 47% identity with HexB of S. pneumoniae. Functional
      analysis of the mutSL locus was studied by constructing a double knock-out
      mutant. We showed that the deletion DeltamutSL induces: (i) a 100- to 1000-fold
      increase in the spontaneous mutation rate; and (ii) a 10- to 15-fold increase in
      the frequency of transduction, thus demonstrating the role of mutSL of L.
      monocytogenes in both mismatch repair and homologous recombination. We found that
      the deletion DeltamutSL moderately affected bacterial virulence, with a 1-log
      increase in the lethal dose 50% (LD50) in the mouse. Strikingly, repeated
      passages of the mutant strain in mice reduced virulence further. Competition
      assays between wild-type and mutant strains showed that the deletion DeltamutSL
      reduced the capacity of L. monocytogenes to survive and multiply in mice. These
      results thus demonstrate that, for the intracellular pathogen L. monocytogenes, a
      hypermutator phenotype is more deleterious than profitable to its virulence.

PMID- 11994167
TI  - A current dilemma in histopathology: atypical spitz tumor or Spitzoid melanoma?
AB  - Both clinically and histopathologically, melanoma of childhood is a rarely
      encountered lesion. In addition, it has particular histopathologic diagnostic
      problems. Differential diagnosis of this lesion and Spitz nevus is at times very
      problematic, in that distant metastases and death of the patient may be the only
      diagnostic criteria for some cases. We present a 4-year-old girl with an atypical
      melanocytic neoplasm with Spitzoid features on the left subscapular region.

PMID- 11994168
TI  - Epidemiology of dermatophytoses in children living in northeast France: a 5-year
      study.
AB  - Dermatologic fungal infections are thought to occur less frequently in children
      than in adults. This study, performed over a 5-year period, emphasizes the
      interregional variability of dermatophytes that cause skin and cutaneous
      apprendageal diseases in children. In northeast France, two-thirds of
      dermatophytoses are due to zoophilic fungi, while they are most commonly caused
      by anthropophilic agents in the Paris region and in other countries. The clinical
      features of pediatric dermatophytoses vary with the age of the child: tinea
      capitis and tinea corporis are far more frequent before the age of 12 years.
      After the age of 12, even if these are still quite frequent, tinea pedis and
      onychomycosis become more common.

PMID- 11994169
TI  - Prominent pruritic periumbilical papules: allergic contact dermatitis to nickel.
AB  - We report a case series of 38 children with suspected allergic contact dermatitis
      (ACD) to nickel who presented with prominent subumbilical and periumbilical
      papules and a generalized, lichenoid papular dermatitis resembling an id
      reaction. We speculated that this was an ACD to nickel and performed patch tests
      in 9 (24%) of these patients. All 9 (100%) patients had positive patch test
      results for nickel, thus confirming the diagnosis.

PMID- 11994170
TI  - Nickel contact hypersensitivity in children.
AB  - Nickel allergic contact dermatitis is the most prevalent allergy in North
      America, with an incidence of 14.3%. It is on the rise from 10 years ago, when
      the incidence was 10%. This has been presumed to represent an increased exposure
      to nickel in the environment-especially in costume jewelry and belt buckles. We
      examined a group of 30 pediatric patients who had either a personal history of
      umbilical or wrist dermatitis, or a family history of nickel allergic contact
      dermatitis. All of these patients had a positive patch test to nickel sulfate 5%.
      Moreover, 50% of patients had an id reaction; all of these patients had positive
      patch tests that were papular in nature, similar to their papular id reaction. We
      posit that the presence of a positive family history may be a positive predictor
      of nickel allergic contact dermatitis, requiring nickel avoidance, especially in
      atopic children. Based on the high level of positive reactions in patients with
      umbilical dermatitis and an id reaction, patch testing to nickel in these
      patients is most likely to yield a useful result. Knowledge of reactivity to
      nickel would then allow parents and patients to initiate nickel avoidance earlier
      in life.

PMID- 11994171
TI  - Congenital generalized terminal hypertrichosis with gingival hyperplasia.
AB  - Congenital generalized terminal hypertrichosis is a rare disease, especially when
      associated with gingival hyperplasia. Congenital hypertrichosis can be a clinical
      feature of several syndromes, so these patients must be studied by a
      multidisciplinary team that should include a dermatologist, geneticist,
      psychologist, odontologist, and an endocrinologist. We report a 7-year-old girl
      with congenital generalized hypertrichosis and gingival hyperplasia, and analyze
      the clinical approach, differential diagnosis, and treatment.

PMID- 11994172
TI  - Bullous pemphigoid in two young infants.
AB  - Bullous pemphigoid (BP) usually affects the elderly. The disease is uncommon in
      children and only a few cases have been described in infants < or =4 months of
      age. We describe two infants, ages 3 and 4 months, with BP. One infant had a
      recalcitrant course, and responded only to a combination of high-dose oral
      corticosteroids and dapsone.

PMID- 11994173
TI  - Lichen scrofulosorum: a rare manifestation of a common disease.
AB  - Tuberculids develop as hypersensitive immunologic reactions in the skin to an
      occult internal focus of tuberculosis. These eruptive lesions are due to
      hematogenous dissemination of bacilli in a host with a high degree of immunity
      against Mycobacterium tuberculosis. Although rare, these specific lesions are
      important diagnostic markers of tuberculosis. Lichen scrofulosorum is one of the
      recognized tuberculids, usually seen in children and young adults. We report
      three children with lichen scrofulosorum; in two children it developed during
      treatment of tuberculosis. The appearance of lichen scrofulosorum after
      initiation of treatment due to a probable increase in cell-mediated immunity is
      emphasized.

PMID- 11994174
TI  - Temporal triangular alopecia: report of five cases in Asian children.
AB  - Temporal triangular alopecia (TTA) is a nonscarring alopecia first described in
      1905. We report five cases of TTA in Asian children and review the literature.

PMID- 11994175
TI  - Temporal triangular alopecia: report of an African-American child with TTA
      misdiagnosed as refractory tinea capitis.
AB  - Temporal triangular alopecia is an underrecognized form of nonscarring alopecia
      that appears in children between the ages of 3 and 6 years and is often
      misdiagnosed. Increased awareness of this entity is needed to prevent ineffective
      and harmful treatments. We present a case misdiagnosed as tinea capitis in an
      African-American girl, review the literature, and elucidate the major
      differential diagnoses.

PMID- 11994176
TI  - Infrapatellar hypertrichosis: an unusual cutaneous manifestation of juvenile
      dermatomyositis.
AB  - Juvenile dermatomyositis (JDM) is an uncommon inflammatory myopathy with
      characteristic cutaneous manifestations. Certain clinical features such as
      cutaneous calcification, lipoatrophy, and generalized hypertrichosis can occur in
      JDM but are uncommon in the adult form of the disease. We report a young girl who
      presented with dramatic infrapatellar hypertrichosis along with more classic
      clinical signs of JDM, including heliotrope periorbital eruption,
      photosensitivity, and profound proximal muscle weakness. The clinical course was
      favorable, with improvement of cutaneous and muscular abnormalities after
      corticosteroid treatment.

PMID- 11994177
TI  - Nail involvement in lichen striatus.
AB  - Nail involvement in lichen striatus is nearly always accompanied by skin lesions.
      A case of childhood lichen striatus involving the thumb nail is presented.

PMID- 11994178
TI  - Congenital lymphedema and distichiasis.
AB  - Distichiasis is defined as a double row of eyelashes. Inherited forms of
      distichiasis have been associated with early and late-onset congenital
      lymphedema. We report on a child with distichiasis and congenital lymphedema in
      which it is unknown whether the cause of lymphedema was due to a spontaneous
      mutation or acquired secondary to an intrauterine infection. Acquired forms of
      distichiasis are reviewed.

PMID- 11994179
TI  - Anticonvulsant hypersensitivity syndrome.
AB  - Anticonvulsant hypersensitivity syndrome is an acute, life-threatening,
      idiosyncratic drug reaction seen with the aromatic antiepileptic drugs,
      phenytoin, carbamazepine, phenobarbital, and primidone, with frequent cross
      sensitivity. It usually occurs 2-8 weeks after initiation of therapy and the
      hallmark clinical features are fever, rash, and lymphadenopathy. Hematologic
      abnormalities such as eosinophilia, atypical lymphocytes, and internal organ
      involvement also occur with varying severity. A case of hypersensitivity syndrome
      due to carbamazepine with cross sensitivity to phenytoin is reported. It is
      emphasized that this serious drug reaction with diverse clinical presentations
      should be recognized and treated promptly.

PMID- 11994180
TI  - Granular parakeratosis in a child.
AB  - Granular parakeratosis has only recently been described and typically occurs in
      adults. We report the first instance of this condition affecting a child.

PMID- 11994181
TI  - Hereditary hypotrichosis simplex of the scalp.
AB  - Hereditary hypotrichosis simplex of the scalp is a genotrichosis characterized by
      sparse or absent scalp hair without structural defects, in the absence of other
      ectodermal or systemic abnormalities. We describe two Spanish families with
      hypotrichosis of the scalp. We believe these families have Toribio and Quinones
      type hereditary hypotrichosis simplex of the scalp.

PMID- 11994182
TI  - Squamous cell carcinoma in pansclerotic morphea of childhood.
AB  - Squamous cell carcinoma (SCC) has only occasionally been reported in patients
      with systemic sclerosis. It is very rare in morphea. Herein we describe SCC
      presenting as malignant ulcers in pansclerotic morphea of childhood in a 16-year
      old boy.

PMID- 11994183
TI  - Alopecia areata in infants and newborns.
AB  - Alopecia areata is a common cause of nonscarring hair loss in children and
      adults. In newborns and very young infants, however, it is thought to be
      extremely rare. In this article we describe five cases of alopecia areata in
      patients less than 6 months of age and briefly discuss the pertinent differential
      diagnosis of infants and newborns with both patchy and complete hair loss. We
      propose that alopecia areata may be more common in this age group than the
      literature suggests.

PMID- 11994184
TI  - Epidermal grafting for vitiligo in adolescents.
AB  - Vitiligo is a significant problem in children. Many fail to respond to medical
      treatment and require melanocyte replenishment with one of the various surgical
      methods. Epidermal grafting using the tops of suction blisters has been found to
      be the most effective surgical procedure. However, the results of this procedure
      have never been delineated separately in adolescents and children. There are
      certain procedural and outcome differences in epidermal grafting among children
      and adolescents as compared to adults. We performed epidermal grafting in 15
      recalcitrant patches of stable vitiligo in 10 children. Thirteen of 15 patches
      (86.66%) in 8 of the 10 patients (80%) showed more than 75% pigmentation. The
      results were much better than the overall response rate of 62% in 142 patients
      (adults as well as children) found in an earlier study. Literature analysis
      revealed the same trend in other studies.

PMID- 11994185
TI  - "Safe" Spitz and its alternatives.

PMID- 11994186
TI  - Symposium on training demands in Pediatric Dermatology 2001.

PMID- 11994187
TI  - What syndrome is this? Rubenstein-Taybi syndrome.

PMID- 11994189
TI  - Garlic cloves for verruca vulgaris.

PMID- 11994188
TI  - Recalcitrant psoriasiform rash.

PMID- 11994190
TI  - Lipoid proteinosis: a follow-up comment.

PMID- 11994191
TI  - A child with systemic mastocytosis who had a facial appearance resembling an aged
      man.

PMID- 11994192
TI  - Tache cerebrale revisited.

PMID- 11994209
TI  - The complexity and challenge of non-major depression in late life.

PMID- 11994208
TI  - Ethanol and LPS modulate NF-kappaB activation, inducible NO synthase and COX-2
      gene expression in rat liver cells in vivo.
AB  - Ethanol and LPS are immunomodulators, whose actions are associated with the
      activation of the transcription factor, NF-kappaB, that mediates the expression
      of a number of rapid response genes involved in the whole body inflammatory
      response to injury, including transcriptional regulation of iNOS and COX-2. We
      investigated modulation by acute ethanol (EtOH) intoxication, LPS and LPS
      tolerance of NF-kappaB activation in hepatocytes, Kupffer cells and sinusoidal
      endothelial cells (SEC), concurrent regulation of iNOS and COX-2 gene expression
      and the influence of gender on these mechanisms. In vivo EtOH alone or with LPS
      significantly activates NF-kappaB in Kupffer cells and SEC. iNOS gene expression
      in these cells is modulated by LPS+EtOH in a gender- dependent manner. Acute EtOH
      administration enhanced iNOS mRNA in hepatocytes and Kupffer cells.LPS tolerance
      decreased LPS-induced NF-kappaB activation in Kupffer cells, but markedly raised
      iNOS mRNA in all three cell types with gender differences (females being higher).
      In LPS tolerant rats EtOH decreased elevated iNOS mRNA in all cells studied. LPS
      tolerance significantly reduced LPS-induced COX-2 mRNA in SEC, but only
      moderately in Kupffer cells of females, and not at all in males. Since NO is a
      known scavenger of superoxide and therefore protective against oxidative injury
      associated with LPS and acute EtOH intoxication, the gender differential effect
      of LPS+EtOH on iNOS gene expression (reduced only in females) may contribute to
      the greater susceptibility of females to alcoholic liver disease. Suppression of
      COX-2 gene expression in SEC may cause detrimental effects in the hepatic
      microcirculation, associated with cirrhosis.

PMID- 11994210
TI  - The clinical and public health relevance of current research on subthreshold
      depressive symptoms to elderly patients.

PMID- 11994211
TI  - Clinically significant non-major depression: old concepts, new insights.
AB  - Clinically significant non-major depression has been underinvestigated despite
      its high prevalence and public health impact. Although there is an increasing
      recognition of the importance of non-major forms of depression, their nosological
      boundaries and neurobiological mechanisms remain largely unknown. The authors
      discuss the literature pertaining to the current concepts, phenomenology,
      neurobiology, and treatment approaches to geriatric non-major clinically
      significant depression. They examine the similarities and differences between
      various subtypes of depressive disorders and compare non-major, clinically
      significant depression in elderly patients with non-geriatric adult populations.
      They draw conclusions from the published literature and propose clinical criteria
      for the diagnosis of clinically significant non-major depression in elderly
      persons.

PMID- 11994212
TI  - Treatment of minor depression.
AB  - Minor depression is one of the most common types of depressive disorders, but the
      benefit of depression-specific treatments for minor depression is less clear than
      for major depression. The authors reviewed the available evidence-base for the
      treatment of Minor Depression as conceptualized in DSM-IV or RDC, conducting a
      computer literature search to identify randomized treatment trials that included
      minor depression and a control condition, and identifying 10 studies meeting
      these criteria. Effect sizes, defined as difference in proportions, could be
      calculated for eight of the studies, and ranged from 0.46 to -0.08. There was no
      evidence that older persons were less responsive to treatment than younger
      persons. Few studies have been specifically designed to test treatments for minor
      depression. The studies are quite variable. Nonspecific treatment factors common
      to both depression treatments and to active control conditions appear potent and
      may be of benefit for persons with minor depression.

PMID- 11994213
TI  - Adverse life events in elderly patients with major depression or dysthymic
      disorder and in healthy-control subjects.
AB  - The authors compared elderly outpatients (> or =60 years) with major depression
      or dysthymic disorder and healthy-control subjects on the type and subjective
      impact of adverse life events. The Geriatric Adverse Life Events Scale (GALES)
      was developed for this purpose. Fifty patients with major depression, 79 patients
      with dysthymic disorder, and 40 healthy controls completed the GALES. Adverse
      life events during two time periods were assessed: the year before the
      evaluation, and the year before onset of the index episode (patients only).
      During the year before evaluation, patients with major depression reported more
      life events with greater negative impact, particularly for interpersonal
      conflicts, and dysthymic patients scored intermediate between patients and
      controls. Sum scores for perceived stress and negative impact on mood differed
      significantly among the groups: highest for major depression, intermediate for
      dysthymic disorder, and lowest for controls. During the year before onset,
      patients with major depression reported significantly higher sum scores for
      negative impact on mood than patients with dysthymic disorder. On several
      measures, patients with major depression perceived greater negative impact of
      life events than patients with dysthymic disorder and healthy controls,
      particularly for interpersonal conflicts. The subjective impact of adverse life
      events may play an important role in the expression of depressive illness in
      elderly patients, particularly in major depression, and it needs to be considered
      in clinical management.

PMID- 11994214
TI  - Depressive disorders and symptoms in older primary care patients: one-year
      outcomes.
AB  - Syndromically diagnosable and subsyndromal depressions have substantial
      prevalence and functional morbidity among older persons seen in primary care, but
      their naturalistic outcome is largely unknown. The authors describe depressive
      symptoms and syndromes and functional outcomes at 1-year follow-up and examine
      specific outcome predictors in a cohort study using psychopathological, medical,
      and functional assessments at intake and 1-year follow-up. Subjects were 247
      patients over age 60, recruited from private internal medicine offices and a
      university-affiliated family medicine clinic. Multiple-regression techniques
      examined the independent association of intake variables to outcome measures. Of
      the 63 subjects with an active depression diagnosis at study intake, 36 (57%)
      still had an active depression diagnosis at 1 year. The outcome for major
      depression was worse than for minor or subsyndromal depression. Medical illness
      burden and neuroticism were independent predictors of outcome. Major depression
      and depressive symptom severity were independently associated with poorer social
      functioning at follow-up. Depressive conditions had considerable rates of
      persistence, yet the outcome was not uniformly poor. Longer-term naturalistic
      study is needed, as are treatment studies targeting those at highest risk of
      recurrence or chronicity.

PMID- 11994215
TI  - Sex differences in the relationship between subthreshold depression and mortality
      in a community sample of older adults.
AB  - The authors investigated the increased risk of mortality from subthreshold
      depression and examined differences in risk by gender. Data from the Duke
      University Established Populations for Epidemiologic Studies of the Elderly
      (EPESE) longitudinal study of 4,162 community-dwelling adults age 65 or older
      were used for these analyses. Depression was measured with a modified version of
      the Center for Epidemiologic Studies Depression Scale (CES-D). Three follow-up
      periods were assessed, 1986-1989, 1989-1992, and 1992-1996. Using logistic
      regression, they determined the odds of mortality from both CES-D depression (>
      or =9 symptoms) and subthreshold depression (6-8 symptoms) by sex for each follow
      up period, controlling for sociodemographic factors, physical and cognitive
      health and functioning, and health behaviors. CES-D depression was not associated
      with mortality in either men or women. Subthreshold depression was also not
      associated with mortality in men; in women, however, subthreshold depression was
      negatively related to mortality (OR=0.60; p=0.002) across the three periods.
      Subthreshold depression may result in different outcomes in women, possibly
      mediating against mortality.

PMID- 11994216
TI  - Relationship between clinical variables and symptomatic anxiety in late-life
      depression.
AB  - The authors asked whether anxiety that is symptomatic of late-life depression is
      associated with clinical variables besides depression and, if so, how much of the
      variance is explained by this association. Severity of anxiety in 101 elderly
      patients with major depression was measured at index assessment and at
      antidepressant response. The following clinical variables were selected to
      determine whether they were associated with severity of anxiety: depression
      severity, burden of chronic physical illness, cognitive functioning, negative
      life events, life difficulties, and intensity of psychosocial support. Anxiety
      had a statistically significant association with severity of depression and life
      events at index assessment and with severity of depression and life difficulties
      at antidepressant response. In linear-regression models, depression severity
      accounted for the largest proportion of the variance in anxiety at both index
      assessment and response; life events and life difficulties accounted for only 3%
      and 4% of variance, respectively. In this group of elderly depressed patients,
      medical burden, cognitive impairment, and negative psychosocial circumstances did
      not contribute in a clinically significant way to variance in severity of
      symptomatic anxiety.

PMID- 11994217
TI  - Stressful life events interacting with cognitive/personality styles to predict
      late-onset major depression.
AB  - The current work evaluated the interaction of life stressors with
      cognitive/personality styles in predicting late-onset depression in 42 elderly
      outpatients with DSM-IV unipolar Major Depression and 42 nondepressed controls.
      Control subjects were matched to cases on age, sex, race, and years of education.
      As suggested by Beck's cognitive theory of depression, a multivariate model
      indicated that specific stressful-event types interacted with specific
      cognitive/personality styles in strongly predicting depression onset, adjusting
      for the positive associations of medical illness and reduced physical functioning
      with depression.

PMID- 11994218
TI  - Activity loss and depression in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most frequent cause of severe
      vision loss in older persons and is associated with high rates of disability and
      depression. The authors evaluated 51 patients with bilateral AMD to investigate
      the interrelationships of disease severity, disability, and depression and
      focused on loss of valued activities as an emblematic disabling consequence of
      AMD. They characterized depression by the Center for Epidemiologic Studies
      Depression (CES-D) score, a syndromal state based on the CES-D, and as a level of
      distress (Index of Affective Suffering; IAS). Thirty subjects (58.8%) had loss of
      a valued, discretionary activity. They had worse visual acuity and more
      depressive symptoms and were represented in higher IAS levels than other
      subjects. Visual acuity was significantly correlated with IAS levels, but not
      with CES-D scores or syndromal depression. A regression model demonstrated that
      activity loss mediated the relationship between visual acuity and IAS level.
      Affective distress occurs in AMD, largely to the extent that valued activities
      are relinquished because of vision loss. IAS levels best illuminated this
      relationship, suggesting the value of this dimension of affective functioning in
      studies of the consequences of chronic disease.

PMID- 11994219
TI  - Relationship of endogenous levels of sex hormones to cognition and depression in
      frail, elderly women.
AB  - Neuropsychological evaluations and sex hormone assays for 188 elderly, female
      nursing home residents (mean age: 87.8 years; standard deviation: 7.0 years)
      revealed inverse relationships for dehydroepiandrosterone (DHEA) blood levels and
      cognition scores based on the Mini-Mental State Exam and the Test for Severe
      Impairment, as well as for scores of the Immediate Recall, Copy, and Recognition
      tests of the Visual Reproduction subtest of the Wechsler Memory Scale-Revised
      (WMS-R; VR). A positive correlation between estrone and depression approached
      significance, as did the inverse relationships between the Recognition scores of
      the WMS-R; VR with androstenedione. These results and findings of others suggest
      that sex hormone actions in elderly women may differ from those in younger
      populations. A possible stress-related mechanism is also posited.

PMID- 11994220
TI  - Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients
      with progressive dementia.
AB  - Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and
      psychiatric illness is unclear. The authors examined the relationship between
      vitamin B12 serum levels and cognitive and neuropsychiatric symptoms in dementia.
      Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for
      probable or possible Alzheimer disease (AD) underwent comprehensive
      neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty
      seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects
      with low B12 levels were significantly older and had significantly lower scores
      on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale,
      but not a different pattern of cognitive or behavior disturbances compared with
      the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is
      consistent with that found in community-dwelling elderly persons in general but
      is associated with greater overall cognitive impairment.

PMID- 11994221
TI  - Comparison of healthcare utilization and direct costs in three degenerative
      dementias.
AB  - The authors conducted a survey of healthcare utilization in three dementia
      syndromes to determine whether type of dementia influenced utilization or
      resulting direct costs. Patients with Alzheimer disease (n=131), dementia with
      parkinsonism (n=85), and Huntington disease (n=51) were identified from a
      registry and enrolled. Caregivers completed the mailed survey, and direct costs
      were estimated. The presence of dementia with parkinsonism resulted in
      significantly greater utilization of long-term care services and higher total
      direct costs. In all three groups, long-term care costs accounted for the
      majority of direct costs. Unique patterns of utilization and costs are seen in
      specific neurodegenerative dementias.

PMID- 11994222
TI  - Geriatric patients on a substance abuse consultation service.
AB  - The authors describe the demographic and substance use characteristics of older
      adults (N=310) evaluated by a hospital-based substance abuse consultation service
      during a 6-year period and compares them to younger adults evaluated by the
      service. Older adults were more likely to use alcohol and less likely to be
      injection drug users and heroin, cocaine, or polysubstance users. Elderly
      patients were also more likely to be admitted for cardiac or gastrointestinal
      conditions and less likely to be admitted for infections. We estimated that only
      1% of older adults admitted to the hospital were referred for substance abuse
      consultations. Our results suggest that substance use disorders in elderly
      patients are underdiagnosed and undertreated in the hospital setting.

PMID- 11994223
TI  - Citalopram treatment of minor depression in elderly men: an open pilot study.
AB  - Antidepressant pharmacotherapy in elderly patients is challenging. The authors
      examined the use of citalopram to treat late-life minor depression. Ten men (mean
      age: 73+/-2 years) with DSM-IV Minor Depression were administered citalopram 20
      mg/day. Efficacy was measured with the Geriatric Depression Scale (GDS), the
      Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global
      Impressions of Severity (CGI-S) scales. Citalopram was well tolerated, and GDS,
      MADRS, and CGI-S scores decreased after 12 weeks. These findings indicate that
      citalopram is safe and effective in the treatment of late-life minor depression.

PMID- 11994224
TI  - Suppression of catatonia-like signs by lorazepam in nonconvulsive status
      epilepticus without seizure termination.
AB  - Nonconvulsive status epilepticus (NCSE) cannot be reliably distinguished from
      catatonia by signs or symptoms. The authors report on a 68-year-old man with
      endogenous major depression who displayed catatonia-like psychopathology, which
      temporarily disappeared with lorazepam. An EEG then revealed NCSE. Presumably,
      lorazepam suppressed seizure in areas where it had caused clouding of
      consciousness, but it did not suppress all seizure activity. When lorazepam was
      stopped, the catatonia-like delirium returned; it disappeared again with
      valproate administration. This case illustrates that the reduction of signs
      consistent with catatonia by benzodiazepines does not by itself confirm
      catatonia, even in patients with endogenous depression.

PMID- 11994225
TI  - Risperidone-associated priapism in an elderly man.

PMID- 11994226
TI  - Androgen receptor CAG repeats and prostate cancer.
AB  - Prostate cancer is the most common nonskin malignancy and the second leading
      cause of cancer deaths among men in the United States. Prostate cancer
      ([Mendelian Inheritance in Man 176807]) has a complex etiology; presently, age,
      ethnicity, and family history are the most consistently reported risk factors
      associated with disease. Other potential risk and protective factors have also
      been suggested. Androgen, acting through the androgen receptor (AR) is helpful in
      preserving the normal function and structure of the prostate. The AR ([Mendelian
      Inheritance in Man 313700]) is a structurally conserved member of the nuclear
      receptor superfamily of ligand-activated transcription factors. Androgens, such
      as testosterone, are strong tumor promoters, and work with the AR to augment the
      effect of any carcinogens present and stimulate cell division. The CAG repeats
      encode long glutamine homopolymeric amino acid chains in the amino-terminal
      domain of the AR gene. The authors focus on CAG repeat length because recent
      research suggests that men with shorter AR CAG lengths (e.g., < or =22 repeats)
      are at a greater risk of developing prostate cancer than are those with longer
      variants. Among populations studied to date, African Americans appear to have the
      highest frequency of short CAG repeats. Several potential interactions have also
      been explored, including molecular interactions, androgen deprivation therapy,
      and prostate-specific antigen expression. CAG repeat length can be determined
      with high sensitivity and specificity. Presently, there is no recommended
      population screening for AR CAG repeat length.

PMID- 11994227
TI  - Epidemiology of pertussis in a West African community before and after
      introduction of a widespread vaccination program.
AB  - The control of pertussis remains a worldwide concern. Little has been documented
      about its epidemiology in Africa. The authors have studied pertussis in a
      prospective cohort of children in a rural West African community over a 13-year
      period comprising time before and after introduction of a vaccination program.
      Children under age 15 years who were residents of the Niakhar study area in
      Senegal were followed prospectively between January 1984 and December 1996 for
      the occurrence of pertussis. Morbidity and mortality rates were extremely high
      before the launch of immunization. Crude incidence was 183 per 1,000 child-years
      at risk under age 5 years, with a 2.8% case-fatality rate. After the introduction
      of the vaccination program, overall incidence dropped rapidly and dramatically-by
      27% after 3 years and 46% after 6 years. The decline in incidence involved all
      age groups but was most substantial in the group under age 5 years and was
      particularly pronounced in unvaccinated infants. The median age of acquisition of
      the disease rose steadily with population vaccine coverage. This study shows the
      tremendous magnitude of the disease burden in children and the rapid decline
      after vaccination, and it suggests a strong herd-immunity effect.

PMID- 11994228
TI  - Invited commentary: pertussis, a forgotten killer.

PMID- 11994229
TI  - Health-related quality of life in Gulf War era military personnel.
AB  - The Gulf War's impact on veterans' health-related quality of life (HRQL) remains
      unclear. The authors examined the HRQL of military personnel deployed to the Gulf
      War Theater compared with those not deployed. In 1995-1996, a structured,
      population-based telephone survey was conducted 5 years postconflict among a
      cohort originally from Iowa on active duty during the conflict. The sample
      included 4,886 eligible subjects stratified by deployment and military status and
      proportionately distributed within five substrata. The Medical Outcome Study
      Short Form-36 (SF-36) assessed HRQL, and multivariable linear regression
      identified pre- and perideployment risk factors. A total of 3,695 respondents
      (76%) participated. Nondeployed participants reported excellent health more often
      than deployed participants (31% vs. 21%, p < 0.01). SF-36 scores for deployed
      participants were poorer than those for nondeployed controls across all health
      domains. Modifiable factors such as smoking and military preparedness, and other
      factors such as predeployment physical and mental health morbidity, were
      independent risk factors for poorer HRQL after deployment. Deployed veterans
      reported slightly poorer HRQL even after the authors adjusted for other risk
      factors. Further investigation of factors influencing postdeployment HRQL is
      needed. Routine collection of health information by using standardized
      instruments pre- and perideployment should be implemented.

PMID- 11994230
TI  - Are Gulf War veterans experiencing illness due to exposure to smoke from Kuwaiti
      oil well fires? Examination of Department of Defense hospitalization data.
AB  - There has been much concern among the public and veterans that specific
      environmental exposures incurred during the Gulf War were the cause of subsequent
      illness among Gulf War veterans. In this historical cohort study, the authors
      compared the postwar morbidity of US military personnel exposed to smoke from the
      1991 Kuwaiti oil well fires with that of unexposed personnel. Complete exposure
      and demographic data were available for 405,142 active-duty Gulf War veterans who
      did not remain in the region after the war. The authors used data from all
      Department of Defense hospitals for the period August 1, 1991-July 31, 1999 to
      estimate rates of hospitalization due to any cause, hospitalization due to a
      diagnosis in one of 15 major categories, and hospitalization due to one of nine
      diagnoses likely to be manifestations of smoke exposure. Exposures to particulate
      matter from oil-well-fire smoke were based on the integration of meteorologic
      data, diffusion modeling, and troop location data. The authors constructed seven
      exposure groups combining duration and amount of exposure. In Cox modeling, three
      of the 25 models showed an increased adjusted risk of hospitalization. However,
      there was no evidence of a dose-response relation. Despite some limitations,
      these data do not support the hypothesis that Gulf War veterans have an increased
      risk of postwar morbidity from exposure to Kuwaiti oil-well-fire smoke.

PMID- 11994231
TI  - Into the world of illegal drug use: exposure opportunity and other mechanisms
      linking the use of alcohol, tobacco, marijuana, and cocaine.
AB  - Drawing upon an "exposure opportunity" concept described by Wade Hampton Frost,
      the authors studied two mechanisms to help account for prior observations about
      the "stepping-stone" or "gateway" sequences that link the use of alcohol,
      tobacco, marijuana, and cocaine. Data were obtained from four nationally
      representative and independent cross-sectional samples of US household residents
      (n = 44,624 persons aged 12-25 years). Data were gathered using standardized self
      report methods and were analyzed via survival methods. Results indicated that
      users of tobacco and alcohol were more likely than nonusers to have an
      opportunity to try marijuana and were more likely to actually use marijuana once
      a marijuana opportunity had occurred. Opportunity to use cocaine was associated
      with prior marijuana smoking. Among young people with a cocaine opportunity,
      those who had used marijuana were more likely to use cocaine than were those with
      no history of marijuana use. The observed associations did not seem to arise
      solely as a result of young drug users' seeking out opportunities to use drugs.
      Applying Frost's epidemiologic concept of exposure opportunity, the authors offer
      new epidemiologic evidence on the sequences that link earlier use of alcohol and
      tobacco to later illegal drug involvement.

PMID- 11994232
TI  - Foot problems as risk factors of fractures.
AB  - This case-control study examines whether foot problems are risk factors of
      fractures of five sites among people aged 45 years or older at six Kaiser
      Permanente Medical Centers in northern California. From October 1996 to May 2001,
      interviewers collected information through a standardized questionnaire. Incident
      cases of distal forearm (n = 1,000), foot (n = 827), proximal humerus (n = 448),
      shaft of the tibia/fibula (n = 168), and pelvis (n = 172) fractures and 1,913
      controls from the same medical centers were included. After adjustment for
      potential confounders and for each additional foot problem, the odds of a foot
      fracture increased by 8% (adjusted odds ratio = 1.08, 95% confidence interval:
      1.03, 1.13). In contrast, each additional foot problem was associated with a
      reduction in the odds of a forearm fracture (adjusted odds ratio = 0.93, 95%
      confidence interval: 0.89, 0.98). In general, foot problems were not related to
      fractures of other sites, although diabetes, which may result in foot problems,
      increased the odds of a proximal humerus fracture (adjusted odds ratio = 1.65,
      95% confidence interval: 1.20, 2.26). If these findings are supported by data
      from other studies, preventive measures to retard the development of foot
      problems could reduce the incidence of foot fractures.

PMID- 11994233
TI  - Families with birth defects: is birth weight of nonmalformed siblings affected?
AB  - Infants with congenital malformations have on average lower birth weight than do
      infants without malformations. Preterm delivery and low birth weight are known to
      recur in sibships. The aim of the study was to compare the birth weight of
      siblings to malformed infants with the birth weight of infants in families
      without malformed infants. Data were from the Medical Birth Registry in Norway
      from 1967 to 1998. Births were linked to their mothers through the unique
      personal identification number, providing sibship files with the mother as the
      observation unit. The study was based on 551,478 mothers with at least two
      singleton infants and 209,423 mothers with at least three singletons. The authors
      grouped the families according to whether and in which birth order an infant had
      a registered congenital malformation and compared birth weight and gestational
      age between infants of the same birth order in families with malformations and
      without. Overall, in families where one or two infants had a congenital
      malformation, the crude and adjusted mean birth weight of nonmalformed siblings
      did not differ from that of infants in unaffected families, whereas it was
      significantly reduced for the malformed infant itself. We conclude that reduced
      birth weight associated with congenital anomalies is specific to the affected
      pregnancy.

PMID- 11994234
TI  - Population-based trends in pediatric hemolytic uremic syndrome in California,
      1994-1999: substantial underreporting and public health implications.
AB  - This paper describes the epidemiology of childhood hemolytic uremic syndrome
      (HUS) in California, for which hospitalization data were used, and the proportion
      of cases reported to public health authorities. HUS discharge data for children <
      or =17 years of age were extracted from the population-based California Patient
      Discharge Data Set for 1994-1999 and were linked electronically with HUS reports
      to public health authorities. Incidence rates per 100,000 children were
      calculated. The authors identified 585 HUS hospitalizations; 369 were incident
      cases. The average HUS incidence rate was 0.67 (95% confidence interval: 0.61,
      0.74); rates rose modestly from 1994 (0.59, 95% confidence interval: 0.44, 0.78)
      to 1997 (0.80, 95% confidence interval: 0.63, 10.0) and decreased modestly
      thereafter (0.59, 95% confidence interval: 0.45, 0.77). Rates were highest for
      northern California children < or =5 years of age (1.85, 95% confidence interval:
      1.55, 2.19). The hospital case-fatality rate was 2.7% (95% confidence interval:
      1.1, 4.4); the median charge was $39,500 per child. Only 43.9% of HUS cases in
      the California Patient Discharge Data Set were reported to public health
      authorities. Despite heightened efforts to control Shiga toxin-producing
      Escherichia coli exposures (the predominant cause of childhood HUS in the United
      States), HUS incidence rates remained relatively stable in California. Reporting
      HUS cases to public health authorities is important for disease control.

PMID- 11994235
TI  - Association of sexual activity with colonization and vaginal acquisition of group
      B Streptococcus in nonpregnant women.
AB  - In a longitudinal cohort study of 1,248 nonpregnant young women recruited from
      three Pittsburgh, Pennsylvania, health clinics in 1998-2000, the authors
      investigated risk factors associated with vaginal acquisition of group B
      Streptococcus (GBS). Rectal and vaginal swabs for GBS culture and demographic and
      behavioral interview data were obtained from the women at enrollment and at three
      4-month intervals. Cox proportional hazards models were used to evaluate risk
      factors for GBS acquisition among the 1,089 women with follow-up data. At
      enrollment, 365 (29.2%) of the 1,248 study participants were vaginally colonized
      with GBS. Of 767 women who were GBS-negative at enrollment, 344 (44.9%) acquired
      vaginal GBS colonization during follow-up. The following factors were
      independently associated with vaginal acquisition of GBS at the 0.05 significance
      level: African-American race (hazard ratio (HR) = 1.5, 95% confidence interval
      (CI): 1.2, 1.9), having multiple sex partners during the past 4 months (HR = 1.7,
      95% CI: 1.1, 2.5), having frequent sexual intercourse during the past 4 months
      (HR = 1.5, 95% CI: 1.1, 2.2), and having sexual intercourse within the 5 days
      prior to the follow-up visit (HR = 1.6, 95% CI: 1.3, 2.0). These results show
      that sexual activity is an important risk factor for vaginal acquisition of GBS.

PMID- 11994236
TI  - Heritability of symptom domains in otitis media: a longitudinal study of 1,373
      twin pairs.
AB  - Research on risk factors and pathogenesis of otitis media has emphasized the
      environment, but previous twin studies suggest a strong genetic component. In
      those studies, no attempt was made to differentiate the role of initial acute
      infection from the chronic airway blockage that frequently accompanies persistent
      effusion. The authors estimated genetic and environmental determination of both
      of these aspects of otitis media histories at three time points. A large and
      representative subset of a total population cohort of all twins born in England
      and Wales in 1994, was studied prospectively at ages 2, 3, and 4 years
      (monozygotic, n = 715; dizygotic, n = 658). For the total symptom score, the
      estimated heritabilities at ages 2, 3, and 4 years were 0.49, 0.66, and 0.71,
      respectively. All correlations for the total score found in monozygotic twins
      were about 0.9, but correlations were lower for dizygotic twins (p < 0.65).
      Shared environmental influences declined in importance over time (0.41, 0.22, and
      0.16 at ages 2, 3, and 4 years, respectively). No gender differences were found
      in parameter estimates. Symptoms of acute infections showed lower heritability
      (0.57 on average) and higher shared environment (0.18) than did chronic airway
      blockage (0.72 heritability and 0.10 shared environment). The strong genetic
      component, which this study confirms, is not unitary but distributes differently
      across the phenotypic aspects of otitis media and probably across pathogenetic
      stage.

PMID- 11994237
TI  - Validation of self-reported chronic obstructive pulmonary disease in a cohort
      study of nurses.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of
      death, and its prevalence is increasing; however, few strategies are available
      for disease prevention or modification besides smoking interventions. To
      facilitate examination of modifiable risk factors for COPD in the Nurses' Health
      Study, the authors validated a questionnaire-based definition of COPD in a subset
      of this US cohort. Participants were surveyed biennially about lifestyle factors,
      including smoking, since 1976 and physician diagnosis of COPD since 1988. Self
      reported cases were defined as reporting COPD on both the original (1988-1996)
      and supplemental (1998) questionnaires. The authors requested medical records for
      a 10% random sample of 2,790 cases and reviewed these records in a systematic,
      blinded fashion. Validated cases required obstructive spirometry, emphysema on
      chest radiograph or computed tomography, or physician diagnosis. COPD was
      confirmed for 78% of 273 cases. Spirometry or radiographic results were available
      for 84%; when available, mean forced expiratory volume in 1 second was 51%
      predicted (standard deviation, 19). Applying these results to a hypothetical
      cohort, the authors estimated the degree to which disease misclassification
      biases relative risks toward the null value, confirming that questionnaire-based
      COPD research should focus on minimizing false positives rather than false
      negatives. In conclusion, COPD can be studied in large, questionnaire-based
      cohorts of health professionals.

PMID- 11994238
TI  - Reliability of random digit dialing calls to enumerate an adult female
      population.
AB  - Challenges to random digit dialing have been documented, but the reliability of
      random digit dialing outcomes from telephone number calling, household
      identification, and enumeration has never been addressed, despite its potential
      to bias population representativeness by affecting completeness of coverage. The
      authors explored interobserver reliability of calls to numbers generated by
      random digit dialing for a 1990-1996 population-based case-control study in San
      Francisco, California, area women, using data from a quality control effort in
      which 122 of 4,890 random digit dialing numbers were assigned to a second
      interviewer for recontacting within 4 months. The 34 numbers discrepant between
      the first and second calls did not differ from the 88 unchanged outcomes, and
      reliability was good (kappa = 0.65, 95% confidence interval: 0.55, 0.75).
      Eligibility (an adult woman in the household) was confirmed for nine of 11
      eligible households. However, six of 29 households originally ineligible because
      of gender were eligible on recontact, and eligible residences rose from 24% to
      39% between the two calls, although the two groups of eligible women did not
      differ in age or race. This underenumeration of women by random digit dialing
      confirms prior observations, although interviewer differences or changes in
      respondents or household composition between the first and second calls may have
      contributed. Recontact of gender-ineligible households may improve completeness
      of random digit dialing coverage for female populations.

PMID- 11994239
TI  - Re: "Presenting statistical uncertainty in trends and dose-response relations".

PMID- 11994242
TI  - Platelet-monocyte aggregates: bridging thrombosis and inflammation.

PMID- 11994243
TI  - Nitric oxide and angiogenesis.

PMID- 11994244
TI  - Cardiology patient pages. Cardiac pacemakers from the patient's perspective.

PMID- 11994245
TI  - Lethal perinatal thrombosis in mice resulting from the interaction of tissue
      factor pathway inhibitor deficiency and factor V Leiden.
AB  - BACKGROUND: Factor V Leiden (FVL) is a common genetic risk factor for thrombosis
      in humans. The incomplete penetrance of FVL suggests important contributions from
      other genetic or environmental modifying factors. Variation in the expression of
      tissue factor pathway inhibitor (TFPI) has also been proposed as a risk factor
      for venous thrombosis and has been shown to enhance the prothrombotic effect of
      FVL in vitro. METHODS AND RESULTS: To examine the potential in vivo interaction
      between Tfpi and FvL, we analyzed crosses between mice carrying FvL and a
      deficiency of TFPI. The Fv(Q/Q),Tfpi(+/-) genotype was nearly completely fatal in
      the early perinatal period. Increased fibrin deposition was observed in multiple
      organs from the Fv(Q/Q),Tfpi(+/-) fetuses, suggesting disseminated thrombosis.
      CONCLUSIONS: These observations demonstrate the prothrombotic effect of modest
      variations in the level of TFPI expression and suggest that TFPI could be an
      important genetic modifier for the thrombosis associated with FVL in humans.

PMID- 11994246
TI  - Influenza vaccine pilot study in acute coronary syndromes and planned
      percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndromes
      (FLUVACS) Study.
AB  - BACKGROUND: Recent reports have detected an increase in the number of patients
      with acute coronary syndromes during the flu season. In addition, the World
      Health Organization recommended vaccination against influenza infection for the
      Southern hemisphere in the winter of 2001. We evaluated the preventive impact of
      vaccination on subsequent ischemic events in myocardial infarction patients and
      in subjects undergoing planned percutaneous coronary angioplasty. METHODS AND
      RESULTS: We included 200 myocardial infarction patients admitted in the first 72
      hours and 101 planned angioplasty/stent (PCI) patients without unstable coronary
      artery disease, prior bypass surgery, angioplasty, or tissue necrosis, in a
      prospective, multicenter log during the winter season. Infarct patients received
      a standard therapy and were then randomly allocated in a single-blind manner to
      either a unique intramuscular influenza vaccination or a control group.
      Similarly, PCI patients were allocated to either vaccination or control groups.
      Combined end points (death, reinfarction, and rehospitalization for ischemia)
      were assessed at 6 months' follow-up. The first primary outcome, cardiovascular
      death, occurred in 2% of the patients in the vaccine group compared with 8% in
      the control group (relative risk with vaccine as compared with controls, 0.25;
      95% CI 0.07 to 0.86; P=0.01). The triple composite end point occurred in 11% of
      the patients in the vaccine group compared with 23% in controls (P=0.009).
      CONCLUSIONS: Influenza vaccination may reduce the risk of death and ischemic
      events in patients suffering from infarction and those recovering from
      angioplasty during flu season. This response could be related to a humoral immune
      response with positive consequences during flu seasons.

PMID- 11994247
TI  - No-reflow phenomenon and lesion morphology in patients with acute myocardial
      infarction.
AB  - BACKGROUND: The no-reflow phenomenon is associated with poor functional and
      clinical outcomes for patients with acute myocardial infarction (AMI). In the era
      of primary intervention, accurately identifying lesions at high risk of no reflow
      is of crucial importance. At present, no study into the relationship between
      lesion morphology and no reflow has been performed. The aim of this study was to
      investigate the relationship between preintervention intravascular ultrasound
      (IVUS) lesion morphology and the no-reflow phenomenon. METHODS AND RESULTS: This
      study comprised 100 consecutive patients with AMI who underwent preintervention
      IVUS and were successfully recanalized with primary balloon angioplasty or
      stenting. IVUS was again performed to identify and exclude any mechanical vessel
      obstruction in cases of thrombolysis in myocardial infarction flow grade 0, 1, or
      2 after intervention in the absence of angiographic stenosis. Angiographic no
      reflow was seen in 13 patients (13%). Univariate analysis indicated that
      hypercholesterolemia, fissure and dissection, lipid pool-like image, lesion, and
      reference external elastic membrane cross-sectional area correlate with the no
      reflow phenomenon. Multivariate logistic regression analysis showed that lipid
      pool-like image (P<0.05; odds ratio 118; 95% CI, 1.28 to 11 008) and lesion
      elastic membrane cross-sectional area (P<0.05; odds ratio 1.55; 95% CI 1.01 to
      2.38) are independent predictive factors of no-reflow phenomenon after
      reperfusion for AMI. CONCLUSIONS: Large vessels with lipid pool-like image are at
      high risk for no reflow after primary intervention for AMI. Also, plaque content
      may play a role in damage to the microcirculation after primary intervention for
      AMI.

PMID- 11994248
TI  - Proinsulin is an independent predictor of coronary heart disease: Report from a
      27-year follow-up study.
AB  - BACKGROUND: Some, but not all, studies have reported a relationship between
      plasma insulin and coronary heart disease (CHD). Conventional nonspecific insulin
      assays are also measuring various fractions of proinsulin-like molecules due to
      cross-reactivity. The long-term relationship between proinsulin-like molecules
      and CHD is largely unknown. For this reason, the longitudinal relationships
      between intact proinsulin, split proinsulin, specific insulin, immunoreactive
      insulin, and CHD, were studied in a population-based cohort of 50-year-old men
      (n=874), with a follow-up of 27 years. METHODS AND RESULTS: Fasting proinsulin
      like molecule and specific-insulin concentrations were measured in plasma (stored
      frozen since baseline 1970 to 1973) by specific 2-site immunometric assays.
      Immunoreactive insulin concentrations were determined at baseline. The
      associations between proinsulin-like molecules, specific insulin, immunoreactive
      insulin, and CHD mortality (International Classification of Diseases [9th
      revision] codes 410 to 414) were analyzed using Cox's proportional hazards
      regression and presented as hazard ratios (HRs) with their 95% confidence
      intervals (CIs) for a 1-SD increase in a predictor variable. In the univariate
      analysis, intact proinsulin (HR, 1.69; 95% CI, 1.41 to 2.01) was the strongest
      predictor of death from CHD. In the multivariate analysis, smoking (HR, 1.57; 95%
      CI, 1.03 to 2.38), intact proinsulin (HR, 1.47; 95% CI, 1.18 to 1.82), systolic
      blood pressure (HR, 1.38; 95% CI, 1.14 to 1.66), and LDL/HDL cholesterol ratio
      (HR, 1.31; 95% CI, 1.12 to 1.53) were independent predictors of CHD mortality
      (adjusted for body mass index, triglycerides, and fasting glucose), whereas
      specific insulin and immunoreactive insulin were not (HR, 1.12; 95% CI, 0.90 to
      1.40). The increased risk was restricted to the upper third of the proinsulin
      distribution. CONCLUSION: Increased proinsulin concentrations predict death and
      morbidity caused by CHD over a period of 27 years, independent of other major
      cardiovascular risk factors.

PMID- 11994249
TI  - Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT
      705, in humans: a randomized phase II dose-response study.
AB  - BACKGROUND: Cholesteryl ester transfer protein (CETP) mediates the transfer of
      neutral lipids between lipoproteins. High plasma levels of CETP are correlated
      with low HDL cholesterol levels, a strong risk factor for coronary artery
      disease. In earlier studies, JTT-705, a novel CETP inhibitor, was shown to
      increase plasma HDL cholesterol and to inhibit the progression of atherosclerosis
      in cholesterol-fed rabbits. This study describes the first results using this
      CETP inhibitor in humans. METHODS AND RESULTS: In a randomized, double-blind, and
      placebo-controlled trial, we evaluated the efficacy and safety of daily treatment
      with 300, 600, and 900 mg JTT-705 in 198 healthy subjects with mild
      hyperlipidemia. Treatment with 900 mg JTT-705 for 4 weeks led to a 37% decrease
      in CETP activity (P<0.0001), a 34% increase in HDL cholesterol (P<0.0001), and a
      7% decrease in LDL cholesterol (P=0.017), whereas levels of triglycerides,
      phospholipid transfer protein, and lecithin-cholesterol acyltransferase were
      unaffected. In line with the increase of total HDL, a rise of HDL2, HDL3, and
      apolipoprotein A-I was also noted. JTT-705 showed no toxicity with regard to
      physical examination and routine laboratory tests. CONCLUSIONS: We show that the
      use of the CETP inhibitor JTT-705 in humans is an effective means to raise HDL
      cholesterol levels with minor gastrointestinal side effects (P=0.06). Although
      these results hold promise, further studies are needed to investigate whether the
      observed increase in HDL cholesterol translates into a concomitant reduction in
      coronary artery disease risk.

PMID- 11994251
TI  - Characteristics of wavefront propagation in reentrant circuits causing human
      ventricular tachycardia.
AB  - BACKGROUND: We investigated the relationship between wavefront curvature and
      slowing of conduction both within and outside the diastolic pathway of circuits
      causing ventricular tachycardia (VT) in the infarcted human heart. METHODS AND
      RESULTS: Propagation was determined around the reentrant circuits of 11 VT (cycle
      length, 348+/-75 ms) in 8 patients undergoing high-resolution noncontact mapping.
      The diastolic pathway had a mean wavefront velocity of 0.82+/-0.49 m/s and
      occupied 68+/-7% of VT cycle length. Significant changes (>5 degrees/mm) in
      trajectory of propagation occurred in 8 diastolic pathway segments (10.1+/-3
      degrees/mm) in which wavefront propagation slowed to 0.41+/-0.11 m/s compared
      with the segments immediately preceding (0.91+/-0.16 m/s, P< 0.05) and following
      (1.07+/-0.33, P<0.05) the change in trajectory. At the turning points of entry
      (9.3+/-3.9 degrees/mm) and exit (9.0+/-4.8 degrees/mm) of the diastolic pathway
      propagation, velocity slowed at entry from 1.23+/-0.4 to 0.6+/-0.26 ms (P<0.001)
      and was more rapid at exit turning points (0.8+/-0.25 m/s) (P<0.05). There was an
      inverse relationship between wavefront curvature and velocity, both within and
      outside the diastolic pathway (r=0.46, P=0.0001), and VT cycle length correlated
      with total curvature multiplied by length of the diastolic pathway (P< 0.01).
      CONCLUSIONS: Slowing of propagation in circuits causing VT in the infarcted human
      heart occurs over regions of wavefront turning, with an inverse relationship
      between wavefront curvature and velocity, both within and outside the diastolic
      pathway. Conduction is slower at entry than exit turning points of the diastolic
      pathway but is slowest during turns within the diastolic pathway.

PMID- 11994250
TI  - Increased platelet binding to circulating monocytes in acute coronary syndromes.
AB  - BACKGROUND: Present therapies for acute coronary syndromes aim toward limiting
      platelet-platelet adhesion and aggregation processes. However, platelet-leukocyte
      interactions may contribute importantly to disease progression in the arterial
      wall. Recent studies suggest that prevention of platelet-leukocyte binding via P
      selectin glycoprotein ligand-1 (PSGL-1) may be beneficial in animal models of
      vascular injury. METHODS AND RESULTS: P-selectin-PSGL-1 interactions were found
      to account for most platelet-monocyte binding observed in peripheral blood
      samples from healthy donors. However, a significant component of observed
      adhesion was calcium independent, involving neither PSGL-1 nor P-selectin.
      Platelet-monocyte interactions were examined in 52 patients admitted within 14
      hours of symptom onset, with acute coronary syndromes defined as unstable angina
      (n=12) and acute myocardial infarction (n=13) or noncardiac chest pain (n=27).
      When compared with patients with noncardiac chest pain, significantly elevated
      levels of platelet-monocyte binding were found in patients with acute myocardial
      infarction (70.1+/-15.4% versus 45.4+/-23.3%; P<0.01) and unstable angina (67.4+/
      12.9% versus 45.4+/-23.3%; P>0.01). Calcium-independent platelet-monocyte binding
      was significantly elevated in myocardial infarction patients alone (14.7+/-7.7%
      versus 6.1+/-5.96%; P<0.001). CONCLUSIONS: There is evidence for a significant P
      selectin-independent molecular component to the platelet-monocyte conjugation
      observed in peripheral blood. Patients with myocardial infarction and unstable
      angina demonstrate increased total binding of platelets to monocytes.
      Additionally, calcium-independent adhesion was significantly elevated in patients
      with evidence of myocardial infarction. These findings demonstrate that novel
      cation-independent adhesion mechanisms may mediate platelet-monocyte binding,
      representing a new therapeutic target after vascular injury associated with
      myocardial infarction.

PMID- 11994252
TI  - Adverse neonatal and cardiac outcomes are more common in pregnant women with
      cardiac disease.
AB  - BACKGROUND: Pregnant women with heart disease (HD) are at increased risk for
      cardiac (CV) complications. However, the frequency of neonatal (NE) complications
      in pregnant women with HD relative to pregnant women without HD has not been
      examined. METHODS AND RESULTS: Pregnant women with HD were prospectively
      monitored during 302 pregnancies. The frequency of NE and CV complications was
      compared with those in a control group without HD during 572 pregnancies. The
      frequency of NE complications was higher in the HD group (18% versus 7%; HD
      versus controls). The NE complication rate was lowest in pregnancies of women age
      20 to 35 years who did not smoke during pregnancy, did not receive
      anticoagulants, and had no obstetric risk factors: 4% in control patients, 5% in
      HD patients with no cardiac risk factors for NE complications (left heart
      obstruction, poor functional class, or cyanosis), and 7% in HD patients with > or
      =1 such risk factor. In contrast, the event rate in pregnancies of controls age
      <20 or >35 years who had obstetric risk factors or multiple gestation or who
      smoked was 11%. In the HD group, women age <20 or >35 years who had obstetric
      risk factors or multiple gestation, who smoked, or who received anticoagulants
      experienced an even higher NE complication rate (27% with no cardiac risks for NE
      events and 33% in the presence of >or =1 cardiac risk factors). The frequency of
      CV complications was higher in the HD group (17% versus 0%; HD versus controls).
      CONCLUSION: Pregnant women with HD are at increased risk for both NE and CV
      complications. The risk for NE adverse events in pregnant women with HD is
      highest in those with both obstetric and cardiac risk factors for NE
      complications.

PMID- 11994253
TI  - Angiostatin inhibits coronary angiogenesis during impaired production of nitric
      oxide.
AB  - BACKGROUND: The in vivo mechanism by which inhibition of NO synthase impairs
      ischemia-induced coronary vascular growth is unknown. We hypothesized that
      production of the growth inhibitor angiostatin increases during decreased NO
      production, blunting angiogenesis and collateral growth. METHODS AND RESULTS:
      Measurements were made in myocardial tissue or interstitial fluid (MIF) from dogs
      undergoing repetitive coronary occlusions under control conditions or during
      antagonism of NO synthase (N(G)-nitro-L-arginine methyl ester [L-NAME]) for 7,
      14, or 21 days. A sham group was instrumented identically but received no
      occlusions. In controls, capillary density in the ischemic zone increased
      initially but returned to baseline at the later times. In the L-NAME group,
      capillary density was lower at 7 days compared with that of controls. MIF from
      control dogs induced in vitro endothelial tube formation and cell proliferation,
      significantly greater than that from the L-NAME group. MIF from shams did not
      stimulate tube formation. In controls or shams, tube formation or cell
      proliferation did not change after administration of antiangiostatin, but this
      antibody restored the responses to control levels in the L-NAME group.
      Angiostatin expression in MIF was increased in the L-NAME group compared with
      controls and shams. The activities of tissue matrix metalloproteinases (MMPs) MMP
      2 and MMP-9, which generate angiostatin, were increased in the L-NAME group.
      CONCLUSIONS: Inhibition of NO synthase increased expression of angiostatin and
      activities of MMP-2 and MMP-9. Our findings indicate that angiostatin inhibits
      coronary angiogenesis during compromised NO production and may underscore the
      impairment of coronary angiogenesis during endothelial dysfunction.

PMID- 11994254
TI  - Load-dependent and -independent regulation of proinflammatory cytokine and
      cytokine receptor gene expression in the adult mammalian heart.
AB  - BACKGROUND: Although previous studies have examined the effects of acute
      hemodynamic pressure overload on proinflammatory cytokine gene expression, the
      effects of sustained hemodynamic overloading have not been examined. METHODS AND
      RESULTS: Sustained hemodynamic pressure overloading was produced in mice by
      transverse constriction of the aorta. Proinflammatory cytokine and cytokine
      receptor gene expression were determined by ribonuclease protection assays (RPA)
      at 6 hours and at 3, 7, 14 and 35 days after banding. M-mode echocardiography was
      used to assess left ventricular structure and function at identical time points.
      RPA showed that tumor necrosis factor (TNF), interleukin (IL)-1beta, and IL-6
      mRNA levels were maximal at 6 hours and returned to baseline levels within 72
      hours. There was a significant increase in IL-1RII and IL-6Ralpha receptor mRNA
      levels after overloading but no significant increase in TNFR1, TNFR2, IL-1RI, or
      gp130 mRNA levels. The transient increase in expression of proinflammatory
      cytokine gene expression was not explained by changes in left ventricular loading
      conditions, left ventricular wall stress, desensitization of proinflammatory
      genes, or decreased nuclear factor-kappaB activation. It is interesting that
      transverse constriction of the aorta provoked an increase in the expression of
      tristetraprolin, a homeostatic zinc finger protein that is known to destabilize
      TNF mRNA. CONCLUSION: Sustained hemodynamic overloading provokes a transient
      increase in proinflammatory cytokine and cytokine receptor gene expression;
      however, the decrease in proinflammatory cytokine gene expression occurred in the
      absence of changes in loading conditions, suggesting that the expression of
      proinflammatory cytokines in the heart is regulated, at least in part, by load
      dependent and load-independent mechanisms.

PMID- 11994255
TI  - Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian
      heart through a protein kinase C-dependent pathway.
AB  - BACKGROUND: Previous studies suggest that angiotensin II (Ang II) upregulates the
      expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the
      effect of Ang II on TNF expression in the adult mammalian heart is not known.
      METHODS AND RESULTS: To determine whether Ang II was sufficient to provoke TNF
      biosynthesis in the adult heart, we examined the effects of Ang II in isolated
      buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment
      resulted in a time- and dose-dependent increase in myocardial TNF mRNA and
      protein biosynthesis in the heart as well as in cultured adult cardiac myocytes.
      The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated
      through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist
      (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor
      (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the
      activation of nuclear factor-kappaB and activator protein-1 (AP-1), two
      transcription factors that are important for TNF gene expression. Nuclear factor
      kappaB activation was accompanied by phosphorylation of IkappaBalpha on serine 32
      as well as degradation of IkappaBalpha, suggesting that the effects of Ang II
      were mediated through an IkappaBalpha-dependent pathway. The important role of
      protein kinase C (PKC) was suggested by studies in which a phorbol ester
      triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF
      biosynthesis. CONCLUSIONS: These studies suggest that Ang II provokes TNF
      biosynthesis in the adult mammalian heart through a PKC-dependent pathway.

PMID- 11994256
TI  - Protection of myocytes from hypoxia-reoxygenation injury by nitric oxide is
      mediated by modulation of transforming growth factor-beta1.
AB  - BACKGROUND: Reoxygenation injury is a result of several complex events, including
      release of reactive oxygen species, protein kinase C (PKC) activation, and
      altered expression of transforming growth factor-beta1 (TGF-beta(1)). Nitric
      oxide (NO) generally protects tissues from reperfusion injury. METHODS AND
      RESULTS: We examined the modulation of TGF-beta1 expression and activity and PKC
      activation in cultured rat heart myocytes exposed to a brief period of hypoxia
      reoxygenation (H-R) by NO donor 3-morpholino-sydnonimine (SIN-1). H-R resulted in
      an increased expression of total TGF-beta1 (mRNA and protein) but a decrease in
      the release of active TGF-beta1. Myocyte PKC-alpha protein level was not altered
      by H-R, but its phosphorylation was augmented. Pretreatment of myocytes with SIN
      1 diminished myocyte injury quantified as lactate dehydrogenase release.
      Simultaneously, release of active TGF-beta1 increased and total TGF-beta1
      expression decreased (all P<0.05 versus H-R alone). PKC-alpha phosphorylation
      increased further in cells treated with SIN-1. The effects of SIN-1 were blocked
      by the NO scavenger phenyl-tetramethyl-imidazoline-oxyl-oxide as well as by the
      PKC inhibitor staurosporine. To examine if another NO donor would have a similar
      effect, cardiomyocytes were treated with nitroglycerin before H-R. With
      nitroglycerin treatment, similar to SIN-1 treatment, myocyte injury was
      diminished, TGF-beta1 release increased, and total TGF-beta1 expression
      decreased. CONCLUSIONS: These observations suggest modulation of TGF-beta1
      expression as a novel mechanism of salutary effect of NO donors. PKC-alpha
      activation may play an important role in the protective effect of NO against H-R
      injury.

PMID- 11994257
TI  - Mineralocorticoid receptor antagonism in experimental atherosclerosis.
AB  - BACKGROUND: Aldosterone has been implicated in the effects of angiotensin II in
      the vasculature. We hypothesized that there is local expression of the
      mineralocorticoid receptor (MR) in the vasculature and that the use of a
      selective aldosterone receptor antagonist (SARA) improves endothelial function in
      early atherosclerosis. METHODS AND RESULTS: New Zealand rabbits were placed on
      normal chow or 1% cholesterol diets, randomized to placebo or SARA (eplerenone,
      50 mg/kg twice daily), and killed at the end of 6 weeks for various studies. In
      the hyperlipidemic (HL) chow group, there was a 2.3-fold increase in superoxide
      (O2*-)) generation. SARA normalized O2*- generation in intact aortas and reduced
      NADH and NADPH oxidase activity to basal levels (0.31+/-0.04 and 0.27+/-0.02 in
      HL versus 0.16+/-0.05 and 0.07+/-0.02 in HL-SARA, respectively; P<0.01 by ANOVA).
      This was associated with improvements in peak relaxations to the endothelial
      dependent agonist acetylcholine (82+/-6% in HL-SARA versus 61+/-4 in HL; P<0.01
      by ANOVA; ED(50) 6.8x10(-8) mol/L in HL-SARA and 1.2x10(-7) mol/L in HL; P=NS) to
      near-normal levels. Vessels from the HL group demonstrated hyperreactivity to
      angiotensin II that could not be corrected with SARA. Plasma aldosterone levels
      by radioimmunoassay demonstrated a 4- to 5-fold increase in response to SARA but
      no differences with lipid feeding. Real-time reverse transcriptase-polymerase
      chain reaction studies revealed expression of MR in the aorta of HL rabbits and
      those of controls. CONCLUSIONS: MR antagonism improves endothelial function and
      reduces O2*- generation in diet-induced atherosclerosis. Targeting aldosterone by
      blocking its receptor has potential antiatherosclerotic effects.

PMID- 11994258
TI  - Percutaneous left atrial appendage occlusion (PLAATO) for preventing
      cardioembolism: first experience in canine model.
AB  - BACKGROUND: Atrial fibrillation is associated with a high risk for cardioembolic
      stroke. The left atrial appendage (LAA) is the source of the vast majority of
      these thromboemboli. A novel implanted device for percutaneous LAA transcatheter
      occlusion (PLAATO) has been designed to seal the LAA. The purpose of this study
      was to test the feasibility and safety of transcatheter LAA occlusion in dogs.
      METHODS AND RESULTS: A PLAATO implant was delivered to the LAA through a 12F
      transseptal catheter in 25 dogs. The PLAATO device was repositioned until
      occlusion was seen, or it was recaptured and replaced with a different size. LAA
      sealing was confirmed by intracardiac echocardiography and contrast fluoroscopy.
      Follow-up was performed 2 days to 6 months after implantation. After imaging
      assessment, dogs were euthanized and LAA was examined for device healing,
      migration, perforation, and any thrombosis, both grossly and histologically. The
      LAA was occluded in all cases. No mobile thrombi associated with the implantation
      were seen. Healing on the atrial-facing surface was 90% at 1 month and was
      complete by 3 months, which was confirmed by gross and histological examination.
      Light microscopic examination of brain, kidney, and spleen showed no evidence of
      emboli or infarct. CONCLUSIONS: Transcatheter LAA occlusion is simple and
      feasible. At the follow-up study, the device remained in the LAA, with benign
      healing and no evidence of new thrombus or damage to surrounding structures. This
      new strategy may provide an alternative treatment for patients with nonvalvular
      atrial fibrillation who are less than optimal candidates for warfarin.

PMID- 11994259
TI  - New therapeutic options in congestive heart failure: Part II.

PMID- 11994260
TI  - Images in cardiovascular medicine. Hypertrophic cardiomyopathy in monozygotic
      twins.

PMID- 11994261
TI  - Prevention Conference VI: Diabetes and Cardiovascular Disease: executive summary:
      conference proceeding for healthcare professionals from a special writing group
      of the American Heart Association.

PMID- 11994262
TI  - Images in cardiovascular medicine. Left main rapamycin-coated stent: invasive
      versus noninvasive angiographic follow-up.

PMID- 11994263
TI  - Prevention Conference VI: Diabetes and Cardiovascular disease: Writing Group I:
      epidemiology.

PMID- 11994264
TI  - Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II:
      pathogenesis of atherosclerosis in diabetes.

PMID- 11994265
TI  - Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group III:
      risk assessment in persons with diabetes.

PMID- 11994266
TI  - Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group IV:
      lifestyle and medical management of risk factors.

PMID- 11994267
TI  - Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group V:
      management of cardiovascular-renal complications.

PMID- 11994268
TI  - Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group VI:
      revascularization in diabetic patients.

PMID- 11994270
TI  - Genetic evidence for the essential role of beta-transducin repeat-containing
      protein in the inducible processing of NF-kappa B2/p100.
AB  - Processing of the nf kappa b2 gene product p100 to generate p52 is an important
      step in NF-kappa B regulation. This step is regulated by a nonclassical NF-kappa
      B signaling pathway involving the NF-kappa B-inducing kinase (NIK). NIK induces
      p100 processing by triggering phosphorylation of specific C-terminal serines of
      p100. However, the downstream molecular events leading to p100 processing remain
      unclear. Here we show that NIK induced the physical recruitment of beta
      transducin repeat-containing protein (beta-TrCP), a component of the SCF
      ubiquitin ligase complex, to p100. This event required the phosphorylation sites
      as well as the death domain of p100. Using the RNA interference technique, we
      demonstrated that beta-TrCP is essential for NIK-induced p100 ubiquitination and
      processing. Interestingly the constitutive processing of p100 mutants was
      independent of beta-TrCP. These results suggest that beta-TrCP is an essential
      component of NIK-induced p100 processing.

PMID- 11994271
TI  - A method to identify serine kinase substrates. Akt phosphorylates a novel
      adipocyte protein with a Rab GTPase-activating protein (GAP) domain.
AB  - This study describes a method for the identification of the substrates of
      specific serine kinases. An antibody specific for the phosphomotif generated by
      the kinase is used to isolate phosphorylated substrates by immunoprecipitation,
      and the isolated proteins are identified by tandem mass spectrometry of peptides.
      This method was applied to the identification of substrates for the protein
      kinase Akt, which specifically phosphorylates the RXRXXS/T motif. 3T3-L1
      adipocytes were treated with insulin to activate Akt, and the putative Akt
      substrate proteins were isolated by immunoprecipitation with an antibody against
      the phospho form of this motif. This led to the identification of a novel 160-kDa
      substrate for Akt. The 160-kDa substrate for Akt, which was designated AS160, has
      a Rab GAP domain. Recombinant AS160 was shown to be a substrate for Akt, and two
      sites of phosphorylation, both in RXRXXS/T motifs, were identified by mass
      spectrometry and mutation. Insulin treatment of adipocytes caused AS160 to
      redistribute from the low density microsomes to the cytosol.

PMID- 11994272
TI  - The large conductance potassium channel beta-subunit can interact with and
      modulate the functional properties of a calcium-activated chloride channel,
      CLCA1.
AB  - We have recently compared the biophysical and pharmacological properties of
      native Ca(2+)-activated Cl(-) currents in murine portal vein with mCLCA1 channels
      cloned from murine portal vein myocytes (Britton, F. C., Ohya, S., Horowitz, B.,
      and Greenwood, I. A. (2002) J. Physiol. (Lond.) 539, 107-117). These channels
      shared a similar relative permeability to various anions, but the expressed
      channel current lacked the marked time dependence of the native current. In
      addition, the expressed channel showed a lower Ca(2+) sensitivity than the native
      channel. As non-pore-forming regulatory beta-subunits alter the kinetics and
      increase the Ca(2+) sensitivity of Ca(2+)-dependent K(+) channels (BK channels)
      we investigated whether co-expression of beta-subunits with CLCA1 would alter the
      kinetics/Ca(2+) sensitivity of mCLCA1. Internal dialysis of human embryonic
      kidney cells stably expressing CLCA1 with 500 nM Ca(2+) evoked a significantly
      larger current when the beta-subunit KCNMB1 was co-expressed. In a small number
      of co-transfected cells marked time dependence to the activation kinetics was
      observed. Interaction studies using the mammalian two-hybrid technique
      demonstrated a physical association between CLCA1 and KCNMB1 when co-expressed in
      human embryonic kidney cells. These data suggest that activation of CLCA1 can be
      modified by accessory subunits.

PMID- 11994273
TI  - TAPAS-1, a novel microdomain within the unique N-terminal region of the PDE4A1
      cAMP-specific phosphodiesterase that allows rapid, Ca2+-triggered membrane
      association with selectivity for interaction with phosphatidic acid.
AB  - Here we identify an 11-residue helical module in the unique N-terminal region of
      the cyclic AMP-specific phosphodiesterase PDE4A1 that determines association with
      phospholipid bilayers and shows a profound selectivity for interaction with
      phosphatidic acid (PA). This module contains a core bilayer insertion unit that
      is formed by two tryptophan residues, Trp(19) and Trp(20), whose orientation is
      optimized for bilayer insertion by the Leu(16):Val(17) pairing. Ca(2+), at
      submicromolar levels, interacts with Asp(21) in this module and serves to gate
      bilayer insertion, which is completed within 10 ms. Selectivity for interaction
      with PA is suggested to be achieved primarily through the formation of a charge
      network of the form (Asp(21-):Ca(2+):PA(2-):Lys(24+)) with overall neutrality at
      the bilayer surface. This novel phospholipid-binding domain, which we call TAPAS
      1 (tryptophan anchoring phosphatidic acid selective-binding domain 1), is here
      identified as being responsible for membrane association of the PDE4A1 cAMP
      specific phosphodiesterase. TAPAS-1 may not only serve as a paradigm for other PA
      binding domains but also aid in detecting related phospholipid-binding domains
      and in generating simple chimeras for conferring membrane association and
      intracellular targeting on defined proteins.

PMID- 11994274
TI  - Autocrine human growth hormone inhibits placental transforming growth factor-beta
      gene transcription to prevent apoptosis and allow cell cycle progression of human
      mammary carcinoma cells.
AB  - Multiple cellular effects of human growth hormone (hGH) are mediated by an
      indirect mechanism requiring transcriptional activation of genes encoding protein
      effector molecules such as insulin-like growth factor-1. Such protein effector
      molecules then act directly to mediate the cellular functions of hGH. We report
      here that autocrine hGH production by mammary carcinoma cells specifically
      results in the transcriptional repression of the p53-regulated placental
      transforming growth factor-beta (PTGF-beta) gene. Transcriptional repression of
      the PTGF-beta gene does not require the p53-binding sites in the PTGF-beta
      promoter, and autocrine hGH also desensitized the response of the PTGF-beta
      promoter to p53 overexpression. Transcriptional repression of the PTGF-beta gene
      is accompanied by consequent decreases in its protein product, Smad-mediated
      transcription, and its cellular effects that include cell cycle arrest and
      apoptosis. PTGF-beta specifically inhibited the autocrine hGH-stimulated
      expression of cyclin D1 required for autocrine hGH-stimulated mammary carcinoma
      cell cycle progression. Thus, one mechanism by which autocrine hGH promotes an
      increase in mammary carcinoma cell number is by transcriptional repression of
      protein effector molecules that promote cell cycle arrest and apoptosis. Such
      transcriptional repression of negative regulatory factors, such as PTGF-beta, may
      also be requisite for direct stimulation of mammary carcinoma cell mitogenesis by
      hGH.

PMID- 11994275
TI  - DNA ligase III is degraded by calpain during cell death induced by DNA-damaging
      agents.
AB  - A yeast two-hybrid screen identified the regulatory subunit of the calcium
      dependent protease calpain as a putative DNA ligase III-binding protein. Calpain
      binds to the N-terminal region of DNA ligase III, which contains an acidic
      proline, aspartate, serine, and threonine (PEST) domain frequently present in
      proteins cleaved by calpain. Recombinant DNA ligase III was a substrate for
      calpain degradation in vitro. This calpain-mediated proteolysis was calcium
      dependent and was blocked by the specific calpain inhibitor calpeptin. Western
      blot analysis revealed that DNA ligase III was degraded in human fibrosarcoma
      HT1080 cells following exposure to gamma-radiation. The degradation of DNA ligase
      III was prevented by pretreatment with calpeptin, which protected irradiated
      cells from death. Calpeptin treatment also blocked 9-amino camptothecin-induced
      DNA ligase III proteolysis and simultaneously protected the cells from death.
      HT1080 clones expressing a modified DNA ligase III that lacked a recognizable
      PEST domain were significantly more resistant to killing by gamma-radiation or 9-
      amino camptothecin than were cells that overexpressed the wild-type form of DNA
      ligase III. These data show that calpain-mediated proteolysis of DNA ligase III
      plays an essential role in DNA damage-induced cell death in human cells.

PMID- 11994276
TI  - Dopamine transporters are phosphorylated on N-terminal serines in rat striatum.
AB  - Dopamine transporters (DATs) are neuronal phosphoproteins that clear dopamine
      from the synaptic cleft. Activation of protein kinase C (PKC) and inhibition of
      protein phosphatases by okadaic acid (OA) increase phosphorylation of DAT and
      lead to concomitant reduction in DAT activity and cell surface expression.
      Numerous potential sites for phosphorylation are present on DAT, but the sites
      utilized and their relationship to transport regulation are currently unknown. We
      used peptide mapping and epitope-specific immunoprecipitation to identify the
      region of DAT that undergoes phosphorylation in rat striatal tissue. Phosphoamino
      acid analysis revealed that basal and stimulated samples were phosphorylated
      primarily on serine. Digestion of (32)PO(4)-labeled DAT with trypsin and
      immunoprecipitation with N- or C-terminal specific antisera failed to isolate
      phosphopeptide fragments corresponding to photoaffinity-labeled fragments that
      contain all internal interhelical loops. However, digestion of (32)PO(4)-labeled
      DAT with endoproteinase asp-N and immunoprecipitation with an N-terminal
      antiserum extracted two phosphopeptide fragments from both basal and PKC/OA
      stimulated samples, demonstrating that the N-terminal cytoplasmic tail is a major
      site of phosphorylation. Aminopeptidase treatment of PKC- and/or OA-stimulated
      DAT cleaved essentially all (32)PO(4) label without proteolysis extending past
      transmembrane domains 1 and 2, providing further evidence that most
      phosphorylation sites are near the N terminus and not in intracellular loops or C
      terminal domains. In situ proteolysis of the N-terminal tail indicates that the
      majority of stimulated phosphorylation sites are N-terminal to an antibody
      epitope at residues 42-59. Two-dimensional analysis of purified protein produced
      three tryptic phosphopeptides that may result from phosphorylation of multiple
      sites, but the fragments did not co-migrate with synthetic tryptic peptides
      phosphorylated at serines 2 and 4. These results indicate that most or all of the
      basal and stimulated phosphorylation of DAT in striatal tissue occurs on one or
      more residues in a group of six serines clustered near the distal end of the
      cytoplasmic N terminus.

PMID- 11994277
TI  - Mutating conserved residues in the ribonuclease H domain of Ty3 reverse
      transcriptase affects specialized cleavage events.
AB  - The reverse transcriptase-associated ribonuclease H (RT/RNase H) domains from the
      gypsy group of retrotransposons, of which Ty3 is a member, share considerable
      sequence homology with their retroviral counterparts. However, the gypsy elements
      have a conserved tyrosine (position 459 in Ty3 RT) instead of the conserved
      histidine in the catalytic center of retroviral RTs such as at position 539 of
      HIV-1. In addition, the gypsy group shows conservation of histidine adjacent to
      the third of the metal-chelating carboxylate residues, which is Asp-426 of Ty3
      RT. The role of these and additional catalytic residues was assessed with
      purified recombinant enzymes and through the ability of Ty3 mutants to support
      transposition in Saccaromyces cerevisiae. Although all mutations had minimal
      impact on DNA polymerase function, amidation of Asp-358, Glu-401, and Asp-426
      eliminated Mg(2+)- and Mn(2+)-dependent RNase H function. Replacing His-427 and
      Tyr-459 with Ala and Asp-469 with Asn resulted in reduced RNase H activity in the
      presence of Mg(2+), whereas in the presence of Mn(2+) these mutants displayed a
      lack of turnover. Despite this, mutations at all positions were lethal for
      transposition. To reconcile these apparently contradictory findings, the
      efficiency of specialized RNase H-mediated events was examined for each enzyme.
      Mutants retaining RNase H activity on a heteropolymeric RNA.DNA hybrid failed to
      support DNA strand transfer and release of the (+) strand polypurine tract primer
      from (+) RNA, suggesting that interrupting one or both of these events might
      account for the transposition defect.

PMID- 11994278
TI  - A single transmembrane site in the KCNE-encoded proteins controls the specificity
      of KvLQT1 channel gating.
AB  - KCNEs are a family of genes encoding small integral membrane proteins whose role
      in governing voltage-gated potassium channel gating is emerging. Whether each
      member of this homologous family interacts with channel proteins in the same
      manner is unknown; however, it is clear that the functional effect of each KCNE
      on channel gating is different. The specificity of KCNE1 (minK) and KCNE3 control
      of activation of the potassium channel KvLQT1 maps to a triplet of amino acids
      within the KCNE transmembrane domain by chimera analysis. We now define the
      structural determinants of functional specificity within this triplet. The
      central amino acid of the triplet (Thr-58 of minK and Val-72 of KCNE3) is
      essential for the specific control of voltage-dependent channel activation
      characteristics of both minK and KCNE3. Using site-directed mutations that
      substitute minK and KCNE3 residues, we determined that a hydroxylated central
      amino acid is necessary for the slow sigmoidal activation produced by minK. The
      precise spacing of the hydroxyl group was required for minK-like activation. An
      aliphatic amino acid substituted at position 58 of minK is capable of reproducing
      KCNE3-like kinetics and voltage-independent constitutive current activation. The
      bulk of the central residue is another critical parameter, indicating precise
      positioning of this portion of the KCNE proteins within the channel complex. An
      intermediate phenotype produced by several smaller aliphatic-substituted mutants
      yields conditional voltage independence that is distinct from the voltage
      dependent gating process, suggesting that KCNE3 traps the channel in a stable
      open state. From these results, we propose a model of KCNE-potassium channel
      interaction where the functional consequence depends on the precise contact at a
      single amino acid.

PMID- 11994279
TI  - Rab11-FIP2 functions in transferrin recycling and associates with endosomal
      membranes via its COOH-terminal domain.
AB  - Rab11-FIP2 is a recently described member of the Rip11/Rab11-FIP/Rab coupling
      protein family of Rab11 interacting proteins. Rab11-FIP2 interacts with both
      Rab11 and myosin Vb and co-localizes with Rab11 in both HeLa and Madin-Darby
      canine kidney cells (Hales, C. M., Griner, R., Hobdy-Henderson, K. C., Dorn, M.
      C., Hardy, D., Kumar, R., Navarre, J., Chan, E. K., Lapierre, L. A., and
      Goldenring, J. R. (2001) J. Biol. Chem. 276, 39067-390751). Here, we
      characterized the specificity of the interaction between Rab11-FIP2 and Rab11 and
      report that it does not interact with Rab4, Rab3, Rab5, Rab6, or Rab7. We
      demonstrate that the COOH-terminal region of Rab11-FIP2, which contains the Rab11
      binding domain (RBD), is necessary and sufficient for its early endosomal
      membrane association. In contrast, the amino-terminal region, which contains a
      phospholipid binding C2-domain, by itself was insufficient for membrane binding.
      Expression of a deletion mutant of Rab11-FIP2, containing the RBD, caused
      tubulation of a transferrin receptor-positive early endosomal compartment in HeLa
      cells. Endogenous Rab11 was also associated with this compartment. This phenotype
      cannot be reversed by excess wild-type Rab11, or dominant-positive Rab11
      (Rab11Q70L), suggesting that Rab11-FIP2 functions downstream of Rab11 in
      endosomal trafficking.

PMID- 11994280
TI  - HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival
      pathways in Kaposi's sarcoma cells.
AB  - In this study we found that Tat protected vincristine-treated Kaposi's sarcoma
      cells from apoptosis and from down-regulation of several anti-apoptotic genes
      such as AKT-1, AKT-2, BCL2, BCL-XL, and insulin-like growth factor I and induced
      the de novo expression of the interleukin-3 gene. Moreover, we found that Tat
      enhanced phosphorylation of AKT and BAD proteins. The inhibition of
      phosphatidylinositol 3-kinase with two unrelated pharmacological inhibitors,
      wortmannin and LY294002, abrogated both the anti-apoptotic effect and the
      phosphorylation of AKT induced by Tat. After treatment with Tat, the AKT
      enzymatic activity showed a biphasic increase: an early activation (15 min),
      independent from protein synthesis; and a delayed activation (24 h), which was
      significantly decreased upon blockage of protein synthesis. Experiments with a
      function blocking anti-vascular endothelial cell growth factor receptor-2
      antibody suggested that both the early and delayed AKT activation and the
      protection from apoptosis were triggered by the interaction of Tat with vascular
      endothelial cell growth factor receptor-2. Moreover, experiments with function
      blocking antibodies directed against insulin-like growth factor I/insulin-like
      growth factor I receptor or interleukin-3 indicated their involvement in the
      delayed activation of AKT and their contribution to the anti-apoptotic effect of
      Tat on vincristine-treated Kaposi's sarcoma cells.

PMID- 11994281
TI  - Effective information transfer from the alpha 1b-adrenoceptor to Galpha 11
      requires both beta/gamma interactions and an aromatic group four amino acids from
      the C terminus of the G protein.
AB  - Co-expression of the alpha(1b)-adrenoreceptor and Galpha(11) in cells derived
      from a Galpha(q)/Galpha(11) knock-out mouse allows agonist-mediated elevation of
      intracellular Ca(2+) levels that is transduced by beta/gamma released from the G
      protein alpha subunit. Mutation of Tyr(356) of Galpha(11) to Phe, within a
      receptor contact domain, had little effect on function but this was reduced
      greatly by alteration to Ser and virtually eliminated by conversion to Asp. This
      pattern was replicated following incorporation of each form of Galpha(11) into
      fusion proteins with the alpha(1b)-adrenoreceptor. Following a [(35)S]guanosine
      5'-O-(3-thiotriphosphate) (GTPgammaS) binding assay, immunoprecipitation of the
      wild type alpha(1b)-adrenoreceptor-Galpha(11) fusion protein indicated that the
      agonist phenylephrine stimulated guanine nucleotide exchange on Galpha(11) more
      than 30-fold. Information transfer by agonist was controlled in residue 356
      Galpha(11) mutants with rank order Tyr > Phe > Trp > Ile > Ala = Gln = Arg > Ser
      > Asp, although these alterations did not alter the binding affinity of either
      phenylephrine or an antagonist ligand. Mutation of a beta/gamma contact interface
      in the alpha(1b)-adrenoreceptor-Tyr(356) Galpha(11) fusion protein did not alter
      ligand binding affinity but did reduce greatly beta/gamma binding and
      phenylephrine stimulation of [(35)S]GTPgammaS binding. It also prevented agonist
      elevation of intracellular Ca(2+) levels, as did a mutation in Galpha(11) that
      prevents G protein subunit dissociation. These results indicate that a bulky
      aromatic group is required four amino acids from the C terminus of Galpha(11) to
      maximize information transfer from an agonist-occupied receptor and disprove the
      hypothesis that tyrosine phosphorylation of this residue is required for G
      protein activation (Umemori, H., Inoue, T., Kume, S., Sekiyama, N., Nagao, M.,
      Itoh, H., Nakanishi, S., Mikoshiba, K., and Yamamoto, T. (1997) Science 276, 1878
      1881). This is distinct from Galpha(i1), where hydrophobicity of the amino acid
      is the key determinant at this location. They also further demonstrate a key role
      for the beta/gamma complex in enhancing receptor to G protein alpha subunit
      information transfer.

PMID- 11994282
TI  - Inhibition of Src family kinases blocks epidermal growth factor (EGF)-induced
      activation of Akt, phosphorylation of c-Cbl, and ubiquitination of the EGF
      receptor.
AB  - Stimulation of T47D cells with epidermal growth factor (EGF) results in the
      activation of the intrinsic tyrosine kinases of the receptor and the
      phosphorylation of multiple cellular proteins including the receptor, scaffold
      molecules such as c-Cbl, adapter molecules such as Shc, and the serine/threonine
      protein kinase Akt. We demonstrate that EGF stimulation of T47D cells results in
      the activation of the Src protein-tyrosine kinase and that the Src kinase
      inhibitor PP1 blocks the EGF-induced phosphorylation of c-Cbl but not the
      activation/phosphorylation of the EGF receptor itself. PP1 also blocks EGF
      induced ubiquitination of the EGF receptor, which is presumably mediated by
      phosphorylated c-Cbl. Src is associated with c-Cbl, and we have previously
      demonstrated that the Src-like kinase Fyn can phosphorylate c-Cbl at a preferred
      binding site for the p85 subunit of phosphatidylinositol 3'-kinase. PP1 treatment
      blocks EGF-induced activation of the anti-apoptotic protein kinase Akt suggesting
      that Src may regulate activation of Akt, perhaps by a Src --> c-Cbl -->
      phosphatidylinositol 3'-kinase --> Akt pathway.

PMID- 11994283
TI  - A 15-residue bifunctional element in D-AKAP1 is required for both endoplasmic
      reticulum and mitochondrial targeting.
AB  - The cAMP-dependent protein kinase anchoring protein, d-AKAP1, has two N-terminal
      splice variants. The shorter forms (N0, d-AKAP1a, and -1c) target to
      mitochondria, and the longer forms (N1, d-AKAP1b, and -1d) with 33 additional
      residues N-terminal to N0 target to the endoplasmic reticulum (ER) (Huang, L. J.,
      Wang, L., Ma, Y., Durick, K., Perkins, G., Deerinck, T. J., Ellisman, M. H., and
      Taylor, S. S. (1999) J. Cell Biol. 145, 951-959). In d-AKAP1a, translation may
      initiate from both Met-34 or Met-49 producing two molecules both targeted to
      mitochondria. The shorter molecule contains the 15-residue targeting motif,
      homologous to the N-terminal mitochondrial targeting motif of hexokinase I.
      Extensive mutagenesis showed that one hydrophobic surface of the 15-residue
      hexokinase-homologous segment contained the key elements for mitochondrial
      targeting. The same 15 residues are also part of the ER-targeting signal, but for
      ER targeting multiple hydrophobic residues are required that encompass both
      surfaces of the helix. The different involvement of the same helical motif for
      targeting to the two organelles appears to reflect different modes of interaction
      with the two organelles. This is the first example of a bifunctional helical
      element that is required for both ER and mitochondrion targeting.

PMID- 11994284
TI  - Modulation of Kv4-encoded K(+) currents in the mammalian myocardium by neuronal
      calcium sensor-1.
AB  - Voltage-gated K(+) channels are multimeric proteins, consisting of four pore
      forming alpha-subunits alone or in association with accessory subunits. Recently,
      for example, it was shown that the accessory Kv channel interacting proteins form
      complexes with Kv4 alpha-subunits and modulate Kv4 channel activity. The
      experiments reported here demonstrate that the neuronal calcium sensor protein-1
      (NCS-1), another member of the recoverin-neuronal calcium sensor superfamily, is
      expressed in adult mouse ventricles and that NCS-1 co-immunoprecipitates with
      Kv4.3 from (adult mouse) ventricular extracts. In addition, co-expression studies
      in HEK-293 cells reveal that NCS-1 increases membrane expression of Kv4 alpha
      subunits and functional Kv4-encoded K(+) current densities. Co-expression of NCS
      1 also decreases the rate of inactivation of Kv4 alpha-subunit-encoded K(+)
      currents. In contrast to the pronounced effects of Kv channel interacting
      proteins on Kv4 channel gating, however, NCS-1 co-expression does not measurably
      affect the voltage dependence of steady-state inactivation or the rate of
      recovery from inactivation of Kv4-encoded K(+) currents. Taken together, these
      results suggest that NCS-1 is an accessory subunit of Kv4-encoded I(to,f)
      channels that functions to regulate I(to,f) density in the mammalian myocardium.

PMID- 11994285
TI  - Activation of the insulin gene promoter through a direct effect of hepatocyte
      nuclear factor 4 alpha.
AB  - Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with
      defective glucose-dependent insulin secretion from pancreatic beta cells. MODY1
      is caused by mutation in the transcription factor hepatocyte nuclear factor 4
      alpha (HNF4 alpha). To understand better the MODY1 phenotype, we tested whether
      HNF4 alpha was able to modulate directly the insulin gene promoter. Transfection
      of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold
      activation of a cotransfected reporter plasmid containing the rat insulin I gene
      promoter. Computer analysis revealed a potential HNF4 alpha-binding site between
      nucleotides -57 and -69 of the promoter; mutation of this sequence led to reduced
      ability of HNF4 alpha to activate the promoter. The ability of HNF4 alpha to bind
      this sequence was confirmed using gel shift analysis. In transfected INS-1 beta
      cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the
      insulin gene promoter led to 50-75% reduction in reporter gene activity;
      expression of dominant negative HNF4 alpha led to significant reduction in the
      activity of wild type and both mutated promoters. Thus, in addition to the
      previously described indirect action of HNF4 alpha on insulin gene expression
      mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the
      insulin gene directly, through a previously unrecognized cis element.

PMID- 11994286
TI  - Basic residues in azurocidin/HBP contribute to both heparin binding and
      antimicrobial activity.
AB  - Azurocidin/CAP37/HBP is an antimicrobial and chemotactic protein that is part of
      the innate defenses of human neutrophils. In addition, azurocidin is an inactive
      serine protease homolog with binding sites for diverse ligands including heparin
      and the bovine pancreatic trypsin inhibitor (BPTI). The structure of the protein
      reveals a highly cationic domain concentrated on one side of the molecule and
      responsible for its strong polarity. To investigate the role of this highly basic
      region, we produced three recombinant azurocidin mutant proteins that were
      altered in either one or both of two clusters of 4 basic residues located
      symmetrically on each side of a central cleft in the cationic domain. Two of the
      mutant proteins (Loop 3: R5Q, K6Q, R8Q, and R10Q; Loop 4: R61Q, R62Q, R63Q, and
      R65Q) exhibited little or no change in heparin and BPTI binding or in
      antimicrobial function. In contrast, the Loop 3/Loop 4 mutant (R5Q, K6Q, R8Q,
      R10Q, R61Q, R62Q, R63Q, and R65Q) in which all 8 basic residues were replaced
      showed greatly decreased ability to bind heparin and to kill Escherichia coli and
      Candida albicans. Thus, we report that the 8 basic residues that were altered in
      the Loop 3/Loop 4 mutant contribute to the ability of the wild-type azurocidin
      molecule to bind heparin and to kill E. coli and C. albicans. Because BPTI
      binding was comparable in wild-type and Loop 3/Loop 4 mutant protein, we conclude
      that the same 8 basic residues are not involved in the binding of BPTI to
      azurocidin, supporting the notion that the binding site for BPTI is distinct from
      the site involved in heparin binding and antimicrobial activity. Finally, we show
      that removal of all 4 positively charged amino acids in the 20-44 azurocidin
      sequence (DMC1: R23Q,H24S,H32S,R34Q), a region previously thought to contain an
      antimicrobial domain, does not affect the activity of the protein against E.
      coli, Streptococcus faecalis, and C. albicans.

PMID- 11994287
TI  - Hepatocyte growth factor inhibits anoikis in head and neck squamous cell
      carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B.
AB  - Hepatocyte growth factor (HGF), also known as a scatter factor, regulates a
      variety of biological activities including cell proliferation, survival,
      migration, and angiogenesis. Importantly, HGF and its receptor c-Met have been
      found to be associated with metastasis of human head and neck squamous cell
      carcinoma (HNSCC). Because anoikis resistance plays an important role in tumor
      progression and metastasis, here we examined whether HGF suppressed suspension
      induced apoptosis (anoikis) in HNSCC cells, and if so, we assessed downstream
      signaling pathways mediated by HGF. We found that HNSCC cells underwent anoikis
      upon loss of matrix contact, whereas HGF provided protection against it. HGF
      induced anoikis resistance was found to be dependent on both ERK and Akt
      signaling pathways. The inhibition of either ERK or Akt activation abolished HGF
      mediated survival. Furthermore, we found that HGF did not activate NFkappaB
      transcription in HNSCC cells and that HGF-mediated anoikis resistance was
      independent of NFkappaB. Taken together, our results suggest that anoikis
      resistance induced by HGF may also play an important role in the progression and
      metastasis of HNSCC.

PMID- 11994288
TI  - CD45 controls interleukin-4-mediated IgE class switch recombination in human B
      cells through its function as a Janus kinase phosphatase.
AB  - CD45 plays a critical regulatory role in receptor signaling through its protein
      tyrosine phosphatase and Janus kinase (JAK) phosphatase activities. To
      investigate whether CD45 also plays a regulatory role in Ig class switching in
      human B cells, we examined the effects of CD45 triggering on Ig class switching
      to IgE and its relationship with CD45 JAK phosphatase activity. Anti-CD45
      triggering of CD45 significantly inhibited interleukin-4 + anti-CD40-induced
      switch recombination in a switch recombination vector assay in stably transfected
      Ramos 2G6 human B cells, as well as Ig epsilon germ-line transcription and Smu
      Sepsilon switch recombination in primary human B cells. These negative regulatory
      effects on Ig class switching were concomitant with the ability of CD45 to
      dephosphorylate the induced phosphorylation of JAK1, JAK3, and signal transducer
      and activator of transcription 6, but not on stress-activated/mitogen-activated
      protein kinases. We also showed that phosphorylated JAK1 and JAK3 were directly
      dephosphorylated by recombinant CD45 in vitro. These results indicate that CD45
      is able to function as JAK phosphatase in human B cells and that this activity is
      directly associated with the negative regulation of the class switch
      recombination to IgE. CD45 may be an appropriate target drug for modulating IgE
      in allergic diseases.

PMID- 11994289
TI  - Basal and physiological Ca(2+) leak from the endoplasmic reticulum of pancreatic
      acinar cells. Second messenger-activated channels and translocons.
AB  - We have studied the Ca(2+) leak pathways in the endoplasmic reticulum of
      pancreatic acinar cells by directly measuring Ca(2+) in the endoplasmic reticulum
      ([Ca(2+)](ER)). Cytosolic Ca(2+) ([Ca(2+)](C)) was clamped to the resting level
      by a BAPTA-Ca(2+) mixture. Administration of cholecystokinin within the
      physiological concentration range caused a graded decrease of [Ca(2+)](ER), and
      the rate of Ca(2+) release generated by 10 pm cholecystokinin is at least 3x as
      fast as the basal Ca(2+) leak revealed by inhibition of the endoplasmic reticulum
      Ca(2+)-ATPase. Acetylcholine also evokes a dose-dependent decrease of
      [Ca(2+)](ER), with an EC(50) of 0.98 +/- 0.06 microm. Inhibition of receptors for
      inositol 1,4,5-trisphosphate (IP(3)) by heparin or flunarizine blocks the effect
      of acetylcholine but only partly blocks the effect of cholecystokinin. 8-NH(2)
      cyclic ADP-ribose (20 microm) inhibits the action of cholecystokinin, but not of
      acetylcholine(.) The basal Ca(2+) leak from the endoplasmic reticulum is not
      blocked by antagonists of the IP(3) receptor, the ryanodine receptor, or the
      receptor for nicotinic acid adenine dinucleotide phosphate. However, treatment
      with puromycin (0.1-1 mm) to remove nascent polypeptides from ribosomes increases
      Ca(2+) leak from the endoplasmic reticulum by a mechanism independent of the
      endoplasmic reticulum Ca(2+) pumps and of the receptors for IP(3) or ryanodine.

PMID- 11994290
TI  - Cystic fibrosis transmembrane conductance regulator-dependent up-regulation of
      Kir1.1 (ROMK) renal K+ channels by the epithelial sodium channel.
AB  - The epithelial sodium channel (ENaC) and the secretory potassium channel
      (Kir1.1/ROMK) are expressed in the apical membrane of renal collecting duct
      principal cells where they provide the rate-limiting steps for Na(+) absorption
      and K(+) secretion. The cystic fibrosis transmembrane conductance regulator
      (CFTR) is thought to regulate the function of both ENaC and Kir1.1. We
      hypothesized that CFTR may provide a regulatory link between ENaC and Kir1.1. In
      Xenopus laevis oocytes co-expressing both ENaC and CFTR, the CFTR currents were 3
      fold larger than those in oocytes expressing CFTR alone due to an increased
      expression of CFTR in the plasma membrane. ENaC was also able to increase Kir1.1
      currents through an increase in surface expression, but only in the presence of
      CFTR. In the absence of CFTR, co-expression of ENaC was without effect on Kir1.1.
      ENaC-mediated CFTR-dependent up-regulation of Kir1.1 was reduced with a Liddle's
      syndrome mutant of ENaC. Furthermore, ENaC co-expressed with CFTR was without
      effect on the closely related K(+) channel, Kir4.1. We conclude that ENaC up
      regulates Kir1.1 in a CFTR-dependent manner. CFTR may therefore provide the
      mechanistic link that mediates the coordinated up-regulation of Kir1.1 during the
      stimulation of ENaC by hormones such as aldosterone or antidiuretic hormone.

PMID- 11994291
TI  - A somatic cell genetic system for dissecting hemopoietic cytokine signal
      transduction.
AB  - Somatic cell genetics has proven to be a powerful tool for the dissection of
      cytokine signal transduction pathways. Here we describe a system in which
      interleukin-6 (IL-6) signaling may be dissected using myeloid leukemic M1 cells.
      We utilized two properties of M1 cell differentiation to isolate IL-6
      unresponsive mutants. First, M1 differentiation is associated with cessation of
      cell division. Second, differentiated M1 cells migrate rapidly and form dispersed
      colonies in agar. Mutant clones that are unresponsive to IL-6 are, therefore,
      large and compact as compared with clones derived from IL-6-responsive wild type
      M1 cells. Following spontaneous or chemically induced mutagenesis and selection
      in a high dose of IL-6, we isolated 27 M1 clones unresponsive to IL-6. Three
      harbored mutations that acted in a dominant manner, whereas 24 contained
      recessive mutations. gp130, an IL-6 receptor component, was affected in many
      mutant clones. We show that these clones display IL-6 and leukemia inhibitory
      factor receptors with reduced binding affinities and express gp130 at reduced
      levels. The IL-6-unresponsive phenotype of these mutant clones was fully rescued
      by the transfection of exogenous gp130 DNA. Therefore, this approach targets
      components of the IL-6 signaling pathway and may be suitable to study signaling
      from a variety of cytokines.

PMID- 11994292
TI  - Methionine aminopeptidase 2 is a new target for the metastasis-associated
      protein, S100A4.
AB  - S100A4 is an EF-hand type calcium-binding protein that regulates tumor metastasis
      and a variety of cellular processes via interaction with different target
      proteins. Here we report that S100A4 physically interacts with methionine
      aminopeptidase 2 (MetAP2), the primary target for potent angiogenesis inhibitors,
      fumagillin and ovalicin. Using a yeast two-hybrid screen, S100A4 was found to
      interact with the N-terminal half of MetAP2. In vitro pull-down assays showed
      that S100A4 associates with MetAP2 in a calcium-dependent manner. In addition,
      the binding site of S100A4 was found located within the region between amino acid
      residues 170 and 229 of MetAP2. In vivo interaction of S100A4 with MetAP2 was
      verified by co-immunoprecipitation analysis. Immunofluorescent staining revealed
      that S100A4 and MetAP2 were co-localized in both quiescent and basic fibroblast
      growth factor-treated murine endothelial MSS31 cells, in the latter of which a
      significant change of intracellular distribution of both proteins was observed.
      Although the binding of S100A4 did not affect the in vitro methionine
      aminopeptidase activity of MetAP2, the cytochemical observation suggests a
      possible involvement of S100A4 in the regulation of MetAP2 activity through
      changing its localization, thereby modulating the N-terminal methionine
      processing of nascent substrates. These results may offer an essential clue for
      understanding the functional role of S100A4 in regulating endothelial cell growth
      and tumor metastasis.

PMID- 11994293
TI  - Cysteine-scanning mutagenesis reveals a conformationally sensitive reentrant pore
      loop in the glutamate transporter GLT-1.
AB  - Removal of glutamate from the synaptic cleft by (Na(+) + K(+))-coupled
      transporters prevents neurotoxicity due to elevated concentrations of the
      transmitter. These transporters exhibit an unusual topology, including two
      reentrant loops. Reentrant loop II plays a pivotal role in coupling ion and
      glutamate fluxes. Here we used cysteine-scanning mutagenesis of the GLT-1
      transporter to test the idea that this loop undergoes conformational changes
      following sodium and substrate binding. 15 of 22 consecutive single cysteine
      mutants in the stretch between Gly-422 and Ser-443 exhibited 30-100% of the
      transport activity of the cysteine-less transporter when expressed in HeLa cells.
      The transport activity of 11 of the 15 active mutants including five consecutive
      residues in the ascending limb was inhibited by small hydrophilic
      methanethiosulfonate reagents. The sensitivity of seven cysteine mutants,
      including A438C and S440C, to the reagents was significantly reduced by sodium
      ions, but the opposite was true for A439C. The non-transportable analogue
      dihydrokainate protected at almost all positions throughout the loop, and at two
      of the positions, the analogue protected even in the absence of sodium. Our
      results indicate that reentrant loop II forms part of an aqueous pore, the access
      of which is blocked by the glutamate analogue dihydrokainate, and that sodium
      influences the conformation of this pore-loop.

PMID- 11994294
TI  - WY14,643, a peroxisome proliferator-activated receptor alpha (PPARalpha )
      agonist, improves hepatic and muscle steatosis and reverses insulin resistance in
      lipoatrophic A-ZIP/F-1 mice.
AB  - WY14,643 is a specific peroxisome proliferator-activated receptor alpha
      (PPARalpha) agonist with strong hypolipidemic effects. Here we have examined the
      effect of WY14,643 in the A-ZIP/F-1 mouse, a model of severe lipoatrophic
      diabetes. With 1 week of treatment, all doses of WY14,643 that were tested
      normalized serum triglyceride and fatty acid levels. Glucose and insulin levels
      also improved but only with high doses and longer treatment duration. WY14,643
      reduced liver and muscle triglyceride content and increased levels of mRNA
      encoding fatty acid oxidation enzymes. In liver, the elevated lipogenic mRNA
      profile (including PPARgamma) in A-ZIP/F-1 mice remained unchanged. These results
      suggest that WY14,643 acts by increasing beta-oxidation rather by than decreasing
      lipogenesis or lipid uptake. Hyperinsulinemic euglycemic clamp studies indicated
      that WY14,643 treatment improved liver more than muscle insulin sensitivity and
      that hepatic mRNA levels of gluconeogenic enzymes were reduced. Combination
      treatment with both WY14,643 and a PPARgamma ligand, rosiglitazone, did not lower
      glucose levels more effectively than did treatment with WY14,643 alone. These
      data support the hypothesis that reducing intracellular triglycerides in non
      adipose tissues improves insulin sensitivity and suggest that further
      investigation of the role of PPARalpha agonists in the treatment of lipoatrophic
      diabetes is warranted.

PMID- 11994295
TI  - Protein kinase C and guanosine triphosphate combine to potentiate calcium
      dependent membrane fusion driven by annexin 7.
AB  - Exocytotic secretion is promoted by the concerted action of calcium, guanine
      nucleotide, and protein kinase C. We now show that the calcium-dependent membrane
      fusion activity of annexin 7 in vitro is further potentiated by the combined
      addition of guanine nucleotide and protein kinase C. The observed increment
      involves the simultaneous activation of annexin 7 by these two effectors.
      Guanosine triphosphate (GTP) and its non-hydrolyzable analogues optimally enhance
      the phosphorylation of annexin 7 by protein kinase C in vitro. Reciprocally,
      phosphorylation by protein kinase C significantly potentiates the binding and
      hydrolysis of GTP by annexin 7. Only protein kinase C-dependent phosphorylation
      has a significant positive effect on annexin 7 GTPase, although other protein
      kinases, including cAMP-dependent protein kinase, cGMP-dependent protein kinase,
      and pp60(c-)(src), have been shown to label the protein with high efficiency. In
      vivo, the ratio of bound GDP/GTP and phosphorylation of annexin 7 change in
      direct proportion to the extent of catecholamine release from chromaffin cells in
      response to stimulation by carbachol, or to inhibition by various protein kinase
      C inhibitors. These results thus lead us to hypothesize that annexin 7 may serve
      as a common site of action for calcium, guanine nucleotide, and protein kinase C
      in the exocytotic membrane fusion process in chromaffin cells.

PMID- 11994296
TI  - The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated
      protein kinase through distinct signaling pathways.
AB  - AMP-activated protein kinase (AMPK) is activated within the cell in response to
      multiple stresses that increase the intracellular AMP:ATP ratio. Here we show
      that incubation of muscle cells with the thiazolidinedione, rosiglitazone, leads
      to a dramatic increase in this ratio with the concomitant activation of AMPK.
      This finding raises the possibility that a number of the beneficial effects of
      the thiazolidinediones could be mediated via activation of AMPK. Furthermore, we
      show that in addition to the classical activation pathway, AMPK can also be
      stimulated without changing the levels of adenine nucleotides. In muscle cells,
      both hyperosmotic stress and the anti-diabetic agent, metformin, activate AMPK in
      the absence of any increase in the AMP:ATP ratio. However, although activation is
      no longer dependent on this ratio, it still involves increased phosphorylation of
      threonine 172 within the catalytic (alpha) subunit. AMPK stimulation in response
      to hyperosmotic stress does not appear to involve phosphatidylinositol 3
      phosphate kinase, protein kinase C, mitogen-activated protein (MAP) kinase
      kinase, or p38 MAP kinase alpha or beta. Our results demonstrate that AMPK can be
      activated by at least two distinct signaling mechanisms and suggest that it may
      play a wider role in the cellular stress response than was previously understood.

PMID- 11994297
TI  - The transcription factors GATA4 and dHAND physically interact to synergistically
      activate cardiac gene expression through a p300-dependent mechanism.
AB  - An intricate array of heterogeneous transcription factors participate in
      programming tissue-specific gene expression through combinatorial interactions
      that are unique to a given cell-type. The zinc finger-containing transcription
      factor GATA4, which is widely expressed in mesodermal and endodermal derived
      tissues, is thought to regulate cardiac myocyte-specific gene expression through
      combinatorial interactions with other semi-restricted transcription factors such
      as myocyte enhancer factor 2, nuclear factor of activated T-cells, serum response
      factor, and Nkx2.5. Here we determined that GATA4 also interacts with the cardiac
      expressed basic helix-loop-helix transcription factor dHAND (also known as
      HAND2). GATA4 and dHAND synergistically activated expression of cardiac-specific
      promoters from the atrial natriuretic factor gene, the b-type natriuretic peptide
      gene, and the alpha-myosin heavy chain gene. Using artificial reporter constructs
      this functional synergy was shown to be GATA site-dependent, but E-box site
      independent. A mechanism for the transcriptional synergy was suggested by the
      observation that the bHLH domain of dHAND physically interacted with the C
      terminal zinc finger domain of GATA4 forming a higher order complex. This
      transcriptional synergy observed between GATA4 and dHAND was associated with p300
      recruitment, but not with alterations in DNA binding activity of either factor.
      Moreover, the bHLH domain of dHAND directly interacted with the CH3 domain of
      p300 suggesting the existence of a higher order complex between GATA4, dHAND, and
      p300. Taken together with previous observations, these results suggest the
      existence of an enhanceosome complex comprised of p300 and multiple semi
      restricted transcription factors that together specify tissue-specific gene
      expression in the heart.

PMID- 11994298
TI  - Identification of pp68 as the Tyrosine-phosphorylated Form of SYNCRIP/NSAP1. A
      cytoplasmic RNA-binding protein.
AB  - Recently we reported that osmotic shock increased the insulin-stimulated tyrosine
      phosphorylation of a 68-kDa RNA-binding protein in 3T3-L1 adipocytes (Hresko, R.
      C., and Mueckler, M. (2000) J. Biol. Chem. 275, 18114-18120). In this present
      study we have identified, by MALDI mass spectrometry, pp68 as the tyrosine
      phosphorylated form of synaptotagmin-binding cytoplasmic RNA-interacting protein
      (SYNCRIP)/NSAP1, a newly discovered cytoplasmic RNA-binding protein. Both SYNCRIP
      and pp68 were enriched in free polysomes found in low density microsomes isolated
      from 3T3-L1 adipocytes. In vitro phosphorylation studies revealed that SYNCRIP,
      once extracted from low density microsomes, can be tyrosine phosphorylated using
      purified insulin receptor. Binding of RNA to SYNCRIP specifically inhibited its
      in vitro phosphorylation but had no effect on receptor autophosphorylation or on
      the ability of the receptor to phosphorylate a model substrate, RCM-lysozyme.
      These results raise the possibility that regulation of mRNA translation or
      stability by insulin may involve the phosphorylation of SYNCRIP.

PMID- 11994299
TI  - The extracellular component of a transport metabolon. Extracellular loop 4 of the
      human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV.
AB  - Cytosolic carbonic anhydrase II (CAII) and the cytoplasmic C-terminal tails of
      chloride/bicarbonate anion exchange (AE) proteins associate to form a bicarbonate
      transport metabolon, which maximizes the bicarbonate transport rate. To determine
      whether cell surface-anchored carbonic anhydrase IV (CAIV) interacts with AE
      proteins to accelerate the bicarbonate transport rate, AE1-mediated bicarbonate
      transport was monitored in transfected HEK293 cells. Expression of the inactive
      CAII V143Y mutant blocked the interaction between endogenous cytosolic CAII and
      AE1, AE2, and AE3 and inhibited their transport activity (53 +/- 3, 49 +/- 10,
      and 35 +/- 1% inhibition, respectively). However, in the presence of V143Y CAII,
      expression of CAIV restored full functional activity to AE1, AE2, and AE3 (AE1,
      101 +/- 3; AE2, 85 +/- 5; AE3, 108 +/- 1%). In Triton X-100 extracts of
      transfected HEK293 cells, resolved by sucrose gradient ultracentrifugation, CAIV
      recruitment to the position of AE1 suggested a physical interaction between CAIV
      and AE1. Gel overlay assays showed a specific interaction between CAIV and AE1,
      AE2, and AE3. Glutathione S-transferase pull-down assays revealed that the
      interaction between CAIV and AE1 occurs on the large fourth extracellular loop of
      AE1. We conclude that AE1 and CAIV interact on extracellular loop 4 of AE1,
      forming the extracellular component of a bicarbonate transport metabolon, which
      accelerates the rate of AE-mediated bicarbonate transport.

PMID- 11994300
TI  - Mutational analysis of the transcription factor IIIB-DNA target of Ty3
      retroelement integration.
AB  - The Ty3 retrovirus-like element inserts preferentially at the transcription
      initiation sites of genes transcribed by RNA polymerase III. The requirements for
      transcription factor (TF) IIIC and TFIIIB in Ty3 integration into the two
      initiation sites of the U6 gene carried on pU6LboxB were previously examined. Ty3
      integrates at low but detectable frequencies in the presence of TFIIIB subunits
      Brf1 and TATA-binding protein. Integration increases in the presence of the third
      subunit, Bdp1. TFIIIC is not essential, but the presence of TFIIIC specifies an
      orientation of TFIIIB for transcriptional initiation and directs integration to
      the U6 gene-proximal initiation site. In the current study, recombinant wild type
      TATA-binding protein, wild type and mutant Brf1, and Bdp1 proteins and highly
      purified TFIIIC were used to investigate the roles of specific protein domains in
      Ty3 integration. The amino-terminal half of Brf1, which contains a TFIIB-like
      repeat, contributed more strongly than the carboxyl-terminal half of Brf1 to Ty3
      targeting. Each half of Bdp1 split at amino acid 352 enhanced integration. In the
      presence of TFIIIB and TFIIIC, the pattern of integration extended downstream by
      several base pairs compared with the pattern observed in vitro in the absence of
      TFIIIC and in vivo, suggesting that TFIIIC may not be present on genes targeted
      by Ty3 in vivo. Mutations in Bdp1 that affect its interaction with TFIIIC
      resulted in TFIIIC-independent patterns of Ty3 integration. Brf1 zinc ribbon and
      Bdp1 internal deletion mutants that are competent for polymerase III recruitment
      but defective in promoter opening were competent for Ty3 integration irrespective
      of the state of DNA supercoiling. These results extend the similarities between
      the TFIIIB domains required for transcription and Ty3 integration and also reveal
      requirements that are specific to transcription.

PMID- 11994301
TI  - Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and
      the actin cytoskeleton.
AB  - The affinity of integrin alpha(IIb)beta(3) for fibrinogen is controlled by inside
      out signals that are triggered by agonists like thrombin. Agonist treatment of
      platelets also activates Rap1b, a small GTPase known to promote integrin
      dependent adhesion of other cells. Therefore, we investigated the role of Rap1b
      in alpha(IIb)beta(3) function by viral transduction of GFP-Rap1 chimeras into
      murine megakaryocytes, which exhibit inside-out signaling similar to platelets.
      Expression of constitutively active GFP-Rap1b (V12) had no effect on unstimulated
      megakaryocytes, but it greatly augmented fibrinogen binding to alpha(IIb)beta(3)
      induced by a PAR4 thrombin receptor agonist (p < 0.01). The Rap1b effect was cell
      autonomous and was prevented by pre-treating cells with cytochalasin D or
      latrunculin A to inhibit actin polymerization. Rap1b-dependent fibrinogen binding
      to megakaryocytes was blocked by POW-2, a novel monovalent antibody Fab fragment
      specific for high affinity murine alpha(IIb)beta(3). In contrast to GFP-Rap1b
      (V12), expression of GFP-Rap1GAP, which deactivates endogenous Rap1, inhibited
      agonist-induced fibrinogen binding (p < 0.01), as did dominant-negative GFP-Rap1b
      (N17) (p < 0.05). None of these treatments affected surface expression of
      alpha(IIb)beta(3). These studies establish that Rap1b can augment agonist-induced
      ligand binding to alpha(IIb)beta(3) through effects on integrin affinity,
      possibly by modulating alpha(IIb)beta(3) interactions with the actin
      cytoskeleton.

PMID- 11994302
TI  - Hsc66 substrate specificity is directed toward a discrete region of the iron
      sulfur cluster template protein IscU.
AB  - Hsc66 and Hsc20 comprise a specialized chaperone system important for the
      assembly of iron-sulfur clusters in Escherchia coli. Only a single substrate, the
      Fe/S template protein IscU, has been identified for the Hsc66/Hsc20 system, but
      the mechanism by which Hsc66 selectively binds IscU is unknown. We have
      investigated Hsc66 substrate specificity using phage display and a peptide array
      of IscU. Screening of a heptameric peptide phage display library revealed that
      Hsc66 prefers peptides with a centrally located Pro-Pro motif. Using a cellulose
      bound peptide array of IscU we determined that Hsc66 interacts specifically with
      a region (residues 99-103, LPPVK) that is invariant among all IscU family
      members. A synthetic peptide (ELPPVKIHC) corresponding to IscU residues 98-106
      behaves in a similar manner to native IscU, stimulating the ATPase activity of
      Hsc66 with similar affinity as IscU, preventing Hsc66 suppression of bovine
      rhodanese aggregation, and interacting with the peptide-binding domain of Hsc66.
      Unlike native IscU, however, the synthetic peptide is not bound by Hsc20 and does
      not synergistically stimulate Hsc66 ATPase activity with Hsc20. Our results
      indicate that Hsc66 and Hsc20 recognize distinct regions of IscU and further
      suggest that Hsc66 will not bind LPPVK motifs with high affinity in vivo unless
      they are in the context of native IscU and can be directed to Hsc66 by Hsc20.

PMID- 11994303
TI  - Cell cycle-regulated phosphorylation of the Xenopus polo-like kinase Plx1.
AB  - Polo-like kinases (Plks) control multiple important events during M phase
      progression, but little is known about their activation during the cell cycle.
      The activities of both mammalian Plk1 and Xenopus Plx1 peak during M phase, and
      this activation has been attributed to phosphorylation. However, no
      phosphorylation sites have previously been identified in any member of the Plk
      family. Here we have combined tryptic phosphopeptide mapping with mass
      spectrometry to identify four major phosphorylation sites in Xenopus Plx1. All
      four sites appear to be phosphorylated in a cell cycle-dependent manner.
      Phosphorylations at two sites (Ser-260 and Ser-326) most likely represent
      autophosphorylation events, whereas two other sites (Thr-201 and Ser-340) are
      targeted by upstream kinases. Several recombinant kinases were tested for their
      ability to phosphorylate Plx1 in vitro. Whereas xPlkk1 phosphorylated primarily
      Thr-10, Thr-201 was readily phosphorylated by protein kinase A, and Cdk1/cyclin B
      was identified as a likely kinase acting on Ser-340. Phosphorylation of Ser-340
      was shown to be responsible for the retarded electrophoretic mobility of Plx1
      during M phase, and phosphorylation of Thr-201 was identified as a major
      activating event.

PMID- 11994304
TI  - Identification and biochemical characterization of a novel transcription
      elongation factor, Elongin A3.
AB  - The Elongin complex stimulates the rate of transcription elongation by RNA
      polymerase II by suppressing the transient pausing of the polymerase at many
      sites along the DNA template. Elongin is composed of a transcriptionally active A
      subunit and two small regulatory B and C subunits, the latter binding stably to
      each other to form a binary complex that interacts with Elongin A and strongly
      induces its transcriptional activity. To further understand the role of Elongin A
      in transcriptional regulation by RNA polymerase II, we are attempting to identify
      Elongin A-related proteins. Here, we report on the molecular cloning, expression,
      and biochemical characterization of human Elongin A3, a novel transcription
      elongation factor that exhibits 49 and 81% identity to Elongin A and the recently
      identified Elongin A2, respectively. The mRNA of Elongin A3 is ubiquitously
      expressed, and the protein is localized to the nucleus of cells. Mechanistic
      studies have demonstrated that Elongin A3 possesses similar biochemical features
      to Elongin A2. Both stimulate the rate of transcription elongation by RNA
      polymerase II and are capable of forming a stable complex with Elongin BC. In
      contrast to Elongin A, however, their transcriptional activities are not
      activated by Elongin BC. Structure-function analyses using fusion proteins
      composed of Elongin A3 and Elongin A revealed that the COOH-terminal region of
      Elongin A is important for the activation by Elongin BC.

PMID- 11994305
TI  - A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the
      hRad9 checkpoint complex.
AB  - Rad9, Rad1, and Hus1 are members of the Rad family of checkpoint proteins that
      are required for both DNA replication and DNA damage checkpoints and are thought
      to function as sensors in the DNA integrity checkpoint control. These proteins
      can interact with each other and form a stable proliferating cell nuclear antigen
      related Rad9.Rad1.Hus1 heterotrimeric complex that might encircle DNA at or near
      the damaged sites. In this study, we demonstrate that the human Rad9 (hRad9)
      protein contains a predicted nuclear localization sequence (NLS) near its C
      terminus, which plays an essential role in the hRad9-mediated G(2) checkpoint.
      Deletion experiments indicate that the NLS-containing region of hRad9 is critical
      for the nuclear transport of not only hRad9 but also human Rad1 (hRad1) and human
      Hus1 (hHus1), although this region is not required for hRad9.hRad1.hHus1 complex
      formation. In support of the role that hRad9 NLS plays in the nuclear targeting
      of the hRad9.hRad1.hHus1 complex, overexpression of a deletion mutant of hRad9
      lacking the NLS-containing C-terminal region can bypass the G(2) checkpoint and
      result in cell death after ionizing radiation or hydroxyurea treatment. Moreover,
      knockdown of hRad9 expression by small interfering RNA (siRNA) results in hRad1
      accumulation in the cytoplasm and significantly abrogates the G(2) checkpoint in
      the presence of damaged DNA or incomplete DNA replication. Thus, the C-terminal
      region of human Rad9 protein is important for G(2) checkpoint control by
      operating the transport of the hRad9.hRad1.hHus1 checkpoint complex into the
      nucleus.

PMID- 11994306
TI  - Membrane targeting of ATP-sensitive potassium channel. Effects of glycosylation
      on surface expression.
AB  - Oligosaccharides play significant roles in trafficking, folding, and sorting of
      membrane proteins. Sulfonylurea receptors (SURx), members of the ATP binding
      cassette family of proteins, associate with the inward rectifier Kir6.x to form
      ATP-sensitive potassium channels (K(ATP)). These channels are found on the plasma
      membrane in many tissues and play a pivotal role in synchronizing electrical
      excitability with cell metabolic state. Trafficking defects resulting from three
      independent SUR1 mutations involved in the disease persistent hyperinsulinemic
      hypoglycemia of infancy have been described. Two of these mutations displayed
      notable decreases in glycosylation. Here we have investigated the relationship
      between the two N-linked glycosylation sites (Asn(10) and Asn(1050)) and SUR1
      trafficking. Using patch clamp analysis, surface biotinylation, and
      immunofluorescence microscopy, we demonstrate a significant decrease in surface
      expression of SUR1 single or double glycosylation site mutants (N10Q,N1050Q) when
      co-expressed with Kir6.2. Additionally, we show prominent retention within the ER
      of the SUR1 double glycosylation mutant under the same conditions. Further
      investigation revealed that mutation of the ER retention signal was able to
      partially restore surface expression of the SUR1 double glycosylation mutant.
      These studies suggest that SUR1 glycosylation is a key element for the proper
      trafficking and surface expression of K(ATP) channels.

PMID- 11994307
TI  - Defective ureagenesis in mice carrying a liver-specific disruption of hepatocyte
      nuclear factor 4alpha (HNF4alpha ). HNF4alpha regulates ornithine
      transcarbamylase in vivo.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) regulates the expression of many
      genes preferentially expressed in liver. HNF4alpha-null mice die during
      embryogenesis precluding the analysis of its function in the adult. To circumvent
      this problem, liver-specific HNF4alpha-null mice were produced. Mice lacking
      hepatic HNF4alpha expression exhibited increased serum ammonia and reduced serum
      urea. This disruption in ureagenesis may be explained by a marked decrease in
      expression and activity of hepatic ornithine transcarbamylase (OTC). To determine
      the molecular mechanisms involved in transcriptional regulation of the mouse OTC
      gene, the OTC promoter region was analyzed. Sequence analysis revealed the
      presence of two putative HNF4alpha-binding sites in the mouse OTC promoter
      region. By using transient transfection analysis, it was established that high
      levels of promoter activity were dependent on both HNF4alpha-binding sites and
      the expression of HNF4alpha. Furthermore, the proximal HNF4alpha-binding site was
      found to be more important than the distal one for transactivating OTC promoter.
      These data demonstrate that HNF4alpha is critical for urea homeostasis by direct
      regulation of the OTC gene in vivo.

PMID- 11994308
TI  - Acidic residues in the lactococcal multidrug efflux pump LmrP play critical roles
      in transport of lipophilic cationic compounds.
AB  - The proton motive force-driven efflux pump LmrP confers multidrug resistance on
      Lactococcus lactis cells by extruding a wide variety of lipophilic cationic
      compounds from the inner leaflet of the cytoplasmic membrane to the exterior of
      the cell. LmrP contains one cysteine (Cys(270)), which was replaced by alanine.
      This cysteine-less variant was used in a cysteine scanning accessibility
      approach. All 19 acidic residues in LmrP were replaced one by one by cysteine and
      subsequently challenged with the large thiol reagent fluorescein maleimide. The
      labeling pattern strongly indicates that only three acidic residues (Asp(142),
      Glu(327), and Glu(388)) are membrane-embedded. The roles of these residues in
      drug recognition were evaluated based on transport experiments with two cationic
      substrates, ethidium and Hoechst 33342, after replacing each of these residues
      with cysteine, alanine, lysine, glutamate, or aspartate. The obtained results
      suggest that the negative charges at positions 142 and 327 are not critical for
      the transport function but are important for drug recognition by LmrP.
      Surprisingly, the residues Cys(142) and Cys(327) become accessible for
      fluorescein maleimide upon binding of substrates, indicating a movement of these
      residues from a nonpolar to a polar environment. Substrate binding apparently
      results in a conformational change in this region of the protein and a
      reorientation of a lipid-embedded, hydrophobic substrate-binding site to an
      aqueous substrate translocation pathway.

PMID- 11994309
TI  - A novel, high performance enzyme for starch liquefaction. Discovery and
      optimization of a low pH, thermostable alpha-amylase.
AB  - High throughput screening of microbial DNA libraries was used to identify alpha
      amylases with phenotypic characteristics compatible with large scale corn wet
      milling process conditions. Single and multiorganism DNA libraries originating
      from various environments were targeted for activity and sequence-based screening
      approaches. After initial screening, 15 clones were designated as primary hits
      based upon activity at pH 4.5 or 95 degrees C without addition of endogenous
      Ca(2+). After further characterization, three enzyme candidates were chosen each
      with an exceptional expression of one or more aspects of the necessary phenotype:
      temperature stability, pH optimum, lowered reliance on Ca(2+) and/or enzyme rate.
      To combine the best aspects of the three phenotypes to optimize process
      compatibility, the natural gene homologues were used as a parental sequence set
      for gene reassembly. Approximately 21,000 chimeric daughter sequences were
      generated and subsets screened using a process-specific, high throughput activity
      assay. Gene reassembly resulted in numerous improved mutants with combined
      optimal phenotypes of expression, temperature stability, and pH optimum. After
      biochemical and process-specific characterization of these gene products, one
      alpha-amylase with exceptional process compatibility and economics was
      identified. This paper describes the synergistic approach of combining
      environmental discovery and laboratory evolution for identification and
      optimization of industrially important biocatalysts.

PMID- 11994310
TI  - Filipin prevents pathological prion protein accumulation by reducing endocytosis
      and inducing cellular PrP release.
AB  - Conversion of the normal membrane-bound prion protein (PrP-sen) to its
      pathological isoform (PrP-res) is a key event in the pathogenesis of
      transmissible spongiform encephalopathies. Although the subcellular sites of
      conversion are poorly characterized, several lines of evidence have suggested the
      involvement of membrane lipid rafts in the conversion process. Here we report
      that copper stimulates the endocytosis of PrP-sen via a caveolin-dependent
      pathway in both microglia and neuroblastoma cells. We show that the polyene
      antibiotic filipin both limits endocytosis of PrP-sen and dramatically reduces
      the amount of membrane-bound PrP-sen. This reduction results from a rapid and
      massive release of full matured PrP-sen into the culture medium. Finally, we
      demonstrate that filipin is a potent inhibitor of PrP-res formation into
      chronically infected neuroblastoma cells. Our results reinforce the role of rafts
      in PrP trafficking and raise the possibility that the release of PrP-sen from the
      plasma membrane decreases the amount of available substrate PrP-sen at the
      conversion sites.

PMID- 11994311
TI  - Modulating acetyl-CoA binding in the GCN5 family of histone acetyltransferases.
AB  - The histone acetyltransferase (HAT) GCN5 is the founding member for a family of
      chromatin remodeling enzymes. GCN5 is the catalytic subunit of a large multi
      subunit complex that functions in the regulation of gene activation via
      acetylation of lysine residues within the N-terminal tails of core histone
      proteins. Using acetyl-CoA as a co-substrate, the high affinity binding of acetyl
      CoA is a critical first step in the reaction. Here, we examine the biochemical
      and biological importance of a conserved hydroxyl-bearing residue in signature
      motif A. Interestingly, one major exception is the Saccharomyces cerevisiae GCN5,
      where an alanine (Ala(190)) is located in the corresponding position. In related
      GCN5 family structures, a hydroxyl-containing side chain residue is hydrogen
      bonded to the alpha-phosphate oxygen of CoA. We demonstrate that this key
      hydrogen bond contributes approximately 10-fold to the binding affinity of GCN5
      HATs for acetyl-CoA. Human p300/CBP-associating factor, human GCN5, and
      tetrahymena GCN5 displayed dissociation constants (K(d)) for acetyl-CoA of 0.64
      +/- 0.12, 0.56 +/- 0.15, and 0.62 +/- 0.17 microm, respectively. In contrast, S.
      cerevisiae GCN5 displayed a K(d) of 8.5 microm. When Ala(190) was replaced with
      threonine, the A190T derivative yielded a K(d) value of 0.56 +/- 0.1 microm for
      acetyl-CoA, completely restoring the higher affinity binding seen with the GCN5
      homologs that naturally harbor a threonine at this position. Detailed kinetic
      analyses revealed that the A190T derivative was otherwise catalytically
      indistinguishable from wild type GCN5. We also demonstrate that the A190T allele
      rescued the slow growth phenotype and the defect in HO transcription caused by a
      deletion of GCN5. Furthermore, the A190T allele supported wild type levels of
      transcriptionally targeted and global histone H3 acetylation. In each case, the
      A190T derivative behaved similarly to wild type GCN5, suggesting that the
      efficacy of HAT activity by GCN5 is not limited by the availability of nuclear
      acetyl-CoA pools.

PMID- 11994312
TI  - Tip60 and histone deacetylase 1 regulate androgen receptor activity through
      changes to the acetylation status of the receptor.
AB  - The androgen receptor (AR), a member of the nuclear hormone receptor superfamily,
      is thought to play an important role in the development of prostate cancer. The
      AR is a hormone-dependent transcription factor that activates expression of
      numerous androgen-responsive genes. Histone acetyltransferase-containing proteins
      have been shown to increase activity of several transcription factors, including
      nuclear hormone receptors, by eliciting histone acetylation, which facilitates
      promoter access to the transcriptional machinery. Conversely, histone
      deacetylases (HDACs) have been identified which reduce levels of histone
      acetylation and are associated with transcriptional repression by various
      transcription factors. We have previously shown that Tip60 (Tat-interactive
      protein, 60 kDa) is a bona fide co-activator protein for the AR. Here we show
      that Tip60 directly acetylates the AR, which we demonstrate is a requisite for
      Tip60-mediated transcription. To define a mechanism for repression of AR
      function, we demonstrate that AR activity is specifically down-regulated by the
      histone deacetylase activity of HDAC1. Furthermore, using both mammalian two
      hybrid and immunoprecipitation experiments, we show that AR and HDAC1 interact,
      suggestive of a direct role for down-regulation of AR activity by HDAC1. In
      chromatin immunoprecipitation assays, we provide evidence that AR, Tip60, and
      HDAC1 form a trimeric complex upon the endogenous AR-responsive PSA promoter,
      suggesting that acetylation and deacetylation of the AR is an important mechanism
      for regulating transcriptional activity.

PMID- 11994313
TI  - Alpha spectrin is essential for morphogenesis and body wall muscle formation in
      Caenorhabditis elegans.
AB  - A common feature of multicellular animals is the ubiquitous presence of the
      spectrin cytoskeleton. Although discovered over 30 yr ago, the function of
      spectrin in non-erythrocytes has remained elusive. We have found that the spc-1
      gene encodes the only alpha spectrin gene in the Caenorhabditis elegans genome.
      During embryogenesis, alpha spectrin localizes to the cell membrane in most if
      not all cells, starting at the first cell stage. Interestingly, this localization
      is dependent on beta spectrin but not beta(Heavy) spectrin. Furthermore, analysis
      of spc-1 mutants indicates that beta spectrin requires alpha spectrin to be
      stably recruited to the cell membrane. Animals lacking functional alpha spectrin
      fail to complete embryonic elongation and die just after hatching. These mutant
      animals have defects in the organization of the hypodermal apical actin
      cytoskeleton that is required for elongation. In addition, we find that the
      process of elongation is required for the proper differentiation of the body wall
      muscle. Specifically, when compared with myofilaments in wild-type animals the
      myofilaments of the body wall muscle in mutant animals are abnormally oriented
      relative to the longitudinal axis of the embryo, and the body wall muscle cells
      do not undergo normal cell shape changes.

PMID- 11994314
TI  - Spatial organization of active and inactive genes and noncoding DNA within
      chromosome territories.
AB  - The position of genes within the nucleus has been correlated with their
      transcriptional activity. The interchromosome domain model of nuclear
      organization suggests that genes preferentially locate at the surface of
      chromosome territories. Conversely, high resolution analysis of chromatin fibers
      suggests that chromosome territories do not present accessibility barriers to
      transcription machinery. To clarify the relationship between the organization of
      chromosome territories and gene expression, we have used fluorescence in situ
      hybridization to analyze the spatial organization of a contiguous approximately 1
      Mb stretch of the Wilms' tumor, aniridia, genitourinary anomalies, mental
      retardation syndrome region of the human genome and the syntenic region in the
      mouse. These regions contain constitutively expressed genes, genes with tissue
      restricted patterns of expression, and substantial regions of intergenic DNA. We
      find that there is a spatial organization within territories that is conserved
      between mouse and humans: certain sequences do preferentially locate at the
      periphery of the chromosome territories in both species. However, we do not
      detect genes necessarily at the periphery of chromosome territories or at the
      surface of subchromosomal domains. Intraterritory organization is not different
      among cell types that express different combinations of the genes under study.
      Our data demonstrate that transcription of both ubiquitous and tissue-restricted
      genes is not confined to the periphery of chromosome territories, suggesting that
      the basal transcription machinery and transcription factors can readily gain
      access to the chromosome interior.

PMID- 11994315
TI  - Identification of myogenic-endothelial progenitor cells in the interstitial
      spaces of skeletal muscle.
AB  - Putative myogenic and endothelial (myo-endothelial) cell progenitors were
      identified in the interstitial spaces of murine skeletal muscle by
      immunohistochemistry and immunoelectron microscopy using CD34 antigen.
      Enzymatically isolated cells were characterized by fluorescence-activated cell
      sorting on the basis of cell surface antigen expression, and were sorted as a
      CD34+ and CD45- fraction. Cells in this fraction were approximately 94% positive
      for Sca-1, and mostly negative (<3% positive) for CD14, 31, 49, 144, c-kit, and
      FLK-1. The CD34+/45- cells formed colonies in clonal cell cultures and colony
      forming units displayed the potential to differentiate into adipocytes,
      endothelial, and myogenic cells. The CD34+/45- cells fully differentiated into
      vascular endothelial cells and skeletal muscle fibers in vivo after
      transplantation. Immediately after sorting, CD34+/45- cells expressed only c-met
      mRNA, and did not express any other myogenic cell-related markers such as MyoD,
      myf-5, myf-6, myogenin, M-cadherin, Pax-3, and Pax-7. However, after 3 d of
      culture, these cells expressed mRNA for all myogenic markers. CD34+/45- cells
      were distinct from satellite cells, as they expressed Bcrp1/ABCG2 gene mRNA (Zhou
      et al., 2001). These findings suggest that myo-endothelial progenitors reside in
      the interstitial spaces of mammalian skeletal muscles, and that they can
      potentially contribute to postnatal skeletal muscle growth.

PMID- 11994316
TI  - The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation
      by the myofibroblast in vitro and in vivo.
AB  - Myofibroblasts are specialized fibroblasts responsible for granulation tissue
      contraction and the soft tissue retractions occurring during fibrocontractive
      diseases. The marker of fibroblast-myofibroblast modulation is the neo expression
      of alpha-smooth muscle actin (alpha-SMA), the actin isoform typical of vascular
      smooth muscle cells that has been suggested to play an important role in
      myofibroblast force generation. Actin isoforms differ slightly in their NH2
      terminal sequences; these conserved differences suggest different functions. When
      the NH2-terminal sequence of alpha-SMA Ac-EEED is delivered to cultured
      myofibroblast in the form of a fusion peptide (FP) with a cell penetrating
      sequence, it inhibits their contractile activity; moreover, upon topical
      administration in vivo it inhibits the contraction of rat wound granulation
      tissue. The NH2-terminal peptide of alpha-skeletal actin has no effect on
      myofibroblasts, whereas the NH2-terminal peptide of beta-cytoplasmic actin
      abolishes the immunofluorescence staining for this isoform without influencing
      alpha-SMA distribution and cell contraction. The FPs represent a new tool to
      better understand the specific functions of actin isoforms. Our findings support
      the crucial role of alpha-SMA in wound contraction. The alpha-SMA-FP will be
      useful for the understanding of the mechanisms of connective tissue remodeling;
      moreover, it furnishes the basis for a cytoskeleton-dependent preventive and/or
      therapeutic strategy for fibrocontractive pathological situations.

PMID- 11994317
TI  - Sly1 protein bound to Golgi syntaxin Sed5p allows assembly and contributes to
      specificity of SNARE fusion complexes.
AB  - Fusion of transport vesicles with their target organelles involves specific
      membrane proteins, SNAREs, which form tight complexes bridging the membranes to
      be fused. Evidence from yeast and mammals indicates that Sec1 family proteins act
      as regulators of membrane fusion by binding to the target membrane SNAREs. In
      experiments with purified proteins, we now made the observation that the ER to
      Golgi core SNARE fusion complex could be assembled on syntaxin Sed5p tightly
      bound to the Sec1-related Sly1p. Sly1p also bound to preassembled SNARE complexes
      in vitro and was found to be part of a vesicular/target membrane SNARE complex
      immunoprecipitated from yeast cell lysates. This is in marked contrast to the
      exocytic SNARE assembly in neuronal cells where high affinity binding of N
      Sec1/Munc-18 to syntaxin 1A precluded core SNARE fusion complex formation. We
      also found that the kinetics of SNARE complex formation in vitro with either
      Sly1p-bound or free Sed5p was not significantly different. Importantly, several
      presumably nonphysiological SNARE complexes easily generated with Sed5p did not
      form when the syntaxin was first bound to Sly1p. This indicates for the first
      time that a Sec1 family member contributes to the specificity of SNARE complex
      assembly.

PMID- 11994318
TI  - Remembrance: the Berson and Yalow saga.

PMID- 11994319
TI  - Clinical review 146: The impact of clinical trials on the treatment of diabetes
      mellitus.

PMID- 11994320
TI  - Nonpalpable thyroid nodules--managing an epidemic.

PMID- 11994321
TI  - Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound
      and color-Doppler features.
AB  - The aim of the study was to correlate the sonographic [ultrasound (US)] and color
      Doppler (CFD) findings with the results of US-guided fine needle aspiration
      biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1)
      the relative importance of US features as risk factors of malignancy; and 2) a
      cost-effective management of nonpalpable thyroid nodules. Four hundred ninety
      four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were
      evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology
      were excluded from the study. All patients with suspicious or malignant cytology
      underwent surgery, whereas subjects with benign cytology had clinical and US
      control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%)
      solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer
      prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%).
      Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4%
      of neoplastic lesions, with no significant differences between tumors greater or
      smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87%
      of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern
      in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83),
      intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were
      independent risk factors of malignancy. FNA performed on hypoechoic nodules with
      at least one risk factor was able to identify 87% of the cancers at the expence
      of cytological evaluation of 38.4% of nonpalpable lesions. The majority of
      nonpalpable thyroid tumors can be identified by cytological evaluation of lesions
      presenting hypoechoic appearance in conjunction with one independent risk factor.
      Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis,
      US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular
      margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions
      of the thyroid without risk factors should be followed by means of clinical and
      US evaluation.

PMID- 11994322
TI  - Cortisol, Cushing's Syndrome, and a shrinking brain-new evidence for
      reversibility.

PMID- 11994323
TI  - Loss of brain volume in endogenous Cushing's syndrome and its reversibility after
      correction of hypercortisolism.
AB  - Chronic exposure to excess glucocorticoids results in cognitive and psychological
      impairment. A few studies have indicated that cerebral atrophy can be found in
      patients with Cushing's syndrome (CS), but its evolution after cure has not been
      studied extensively. We report the presence of apparent cerebral atrophy in CS
      and its reversibility after the correction of hypercortisolism. Thirty-eight
      patients with CS, including 21 with Cushing's disease and 17 with adrenal CS were
      studied. The control groups consisted of 18 patients with other non-ACTH
      secreting sellar tumors and 20 normal controls. Twenty-two patients with CS were
      reevaluated after cure. Subjective loss of brain volume was present in 86% of
      patients with Cushing's disease and 100% of patients with adrenal CS. The values
      for third ventricle diameter, bicaudate diameter, and subjective evaluation were
      significantly increased in CS groups in comparison with the control group (P < or
      = 0.001). Imaging reevaluated at 39.7 +/- 34.1 months after achieving
      eucortisolism showed an improvement of the third ventricle diameter (P = 0.001),
      bicaudate diameter (P < 0.0005), and subjective evaluation (P = 0.05). We
      conclude that brain volume loss is highly prevalent in CS and is at least
      partially reversible following correction of hypercortisolism.

PMID- 11994324
TI  - Utility of plasma free metanephrines for detecting childhood pheochromocytoma.
AB  - Measurements of plasma free metanephrines, normetanephrine (NMN) and metanephrine
      (MN), provide a sensitive test for diagnosis of pheochromocytoma in adults but
      have not been evaluated in children. We therefore established reference ranges
      for plasma and urinary metanephrines and the catecholamines, norepinephrine (NE)
      and epinephrine (E), in 86 healthy children (age 5-17). A group of 158 healthy
      adults (age 18-72) served as a comparison group. Pediatric reference ranges were
      applied to examine the diagnostic utility of the various tests in 45 children
      evaluated for pheochromocytoma (age 8-17; 38 with von Hippel-Lindau syndrome),
      with tumors found on 12 occasions. Upper reference limits for E and MN were
      higher and those for NE and NMN lower in children than in adults. Boys had higher
      plasma levels of E and MN and higher urinary excretion of all four amines than
      girls. Plasma free metanephrines provided a diagnostic test with values for
      sensitivity (100%) and specificity (94%) that were equal to or higher than those
      of other tests. In two children screened for pheochromocytoma on multiple
      occasions, use of pediatric reference ranges for plasma free metanephrines
      indicated the tumor a year earlier than indicated using adult reference ranges.
      The findings indicate that plasma free metanephrines provide a sensitive tool for
      detection of pheochromocytoma in children. Age appropriate reference ranges
      should be used and gender differences should be considered.

PMID- 11994325
TI  - GH secretion is impaired in patients with primary hyperparathyroidism.
AB  - The activity of the GH/IGF-I axis as a function of parathyroid activity and
      calcium metabolism in humans has never been assessed. To address this issue, we
      studied 18 patients (5 men, 13 women; age range, 23-76 yr; mean, 61 yr) with
      primary hyperparathyroidism (PHP) due to solitary parathyroid adenoma. GH
      secretion was evaluated by serum IGF-I levels, spontaneous mean GH secretion over
      two morning hours, and GH response to arginine (ARG) alone or combined with GHRH.
      In five patients, serum GH concentrations were measured every 20 min for 24 h,
      and deconvolution analysis was performed. A group of 35 age- and sex-matched
      normal subjects served as controls. Mean serum IGF-I levels in PHP were lower
      than in normal controls, and in six PHP patients individual serum IGF-I levels
      were below the age-related normal range. The mean (+/-SE) peak GH response to ARG
      alone in PHP patients was significantly lower than in normal subjects (4.0 +/-
      1.0 vs. 22.0 +/- 1.3 microg/liter; P < 0.001). Likewise, the mean (+/-SE) peak GH
      response to ARG plus GHRH was reduced in PHP patients (9.9 +/- 0.9 vs. 38.0 +/-
      3.5 microg/liter; P < 0.001). The mean GH concentration over two morning hours in
      PHP was lower (0.20 +/- 0.05 vs. 1.34 +/- 0.31 microg/liter; P < 0.001). The mean
      GH concentration over 24 h in five PHP patients was lower than in six normal
      controls (0.3 +/- 0.1 vs. 0.7+/- 0.1 microg/liter; P < 0.05); the deconvolution
      analysis showed that 24-h GH production rate (3.0 +/- 1.7 vs. 28.2 +/- 4.7
      microg/liter.d; P < 0.05) and mean secretory burst mass (1.2 +/- 0.7 vs. 10.5 +/-
      2.6 microg/liter; P < 0.05), but not pulse frequency, were lower in PHP patients
      than in normal controls. GH half-life and approximate entropy values of 24-h GH
      profiles were similar in PHP patients and normal controls. No correlation was
      found between serum-ionized calcium or PTH levels and spontaneous or stimulated
      GH levels in PHP patients. In conclusion, this study demonstrates that PHP
      patients have a reduction in both spontaneous and stimulated GH secretion.
      Accordingly, PHP should be mentioned as a further example of a metabolic
      condition in which GH secretion in adults is reduced.

PMID- 11994326
TI  - Altered temporal organization of plasma insulin oscillations in chronic renal
      failure.
AB  - Chronic renal failure (CRF) is associated with mechanistically unexplained
      impaired insulin sensitivity. Erratic insulin secretory patterns typify other
      states of insulin resistance. We sought to investigate possible alterations of
      plasma insulin oscillations in CRF. We assessed high- and low-frequency insulin
      and glucose oscillations in 7 male CRF patients and 11 controls by
      multiparametric deconvolution analysis and cluster analysis, approximate entropy
      (ApEn) statistic, and cross-ApEn statistics. Insulin sensitivity was appraised by
      euglycemic hyperinsulinemic clamps. Despite impaired glucose disappearance rates
      in CRF, fasting and 24-h mean insulin and glucose concentrations did not differ
      between patients and controls. However, patients showed a 2.5-fold increase of
      insulin elimination half-life, reduced frequency of both rapid (6.1 +/- 0.4 vs.
      7.1 +/- 0.2 h(-1), P < 0.001) and slow oscillations of insulin release (0.54 +/-
      0.11 vs. 0.71 +/- 0.1 h(-1), P < 0.001), lack of acceleration and paradoxically
      more orderly slow insulin and glucose pulses after meals, and increased temporal
      coupling between insulin and glucose patterns (cross-ApEn: 0.58 +/- 0.13 vs. 1.37
      +/- 0.23, P < 0.001). Postprandial glucose intolerance was inferable by prolonged
      and amplified blood glucose excursions despite exaggerated insulin bursts of
      almost 3-fold higher area. In summary, CRF is associated with a complex
      disruption of the temporal organization of insulin release, which differs from
      abnormalities observed to date in other states of insulin resistance.

PMID- 11994327
TI  - Short-term safety and efficacy of human GH replacement therapy in 595 adults with
      GH deficiency: a comparison of two dosage algorithms.
AB  - The aim of GH replacement therapy in GH-deficient adults is to optimize response
      with minimum incidence of adverse reactions, but optimal therapy regimens are
      still to be established. This two-arm parallel study examined effects of two GH
      dose algorithms in adults with GH deficiency of adult or childhood onset.
      Patients on low dose (LD; n = 302) received GH at 3 microg/kg per day for 3
      months increasing to 6 microg/kg per day for 3 months, and those on conventional
      dose (CD; n = 293) started on 6 microg/kg per day for 3 months increasing to 12
      microg/kg per day for 3 months. The proportion of patients completing therapy was
      greater for the LD group than the CD group for the first 3 months (93.0% vs.
      88.1%; P = 0.037) and overall for the 6 months (90.7% vs. 84.0%; P = 0.013). Both
      dose groups showed significant increases in lean body mass and decreases in fat
      mass for all time points. Percent increase in lean body mass was less with LD
      than CD over the first 3 months (2.43 +/- 4.33 vs. 3.58 +/- 4.69%; P = 0.006) but
      not overall for the 6-month period (4.38% +/- 5.34% vs. 5.21% +/- 5.99%; P =
      0.141). Percent decrease in fat mass was less with LD than CD for the first 3
      months (-2.81% +/- 7.81% vs. -5.53% +/- 8.64%; P < 0.001) and overall for the 6
      month period (-6.35% +/- 9.42% vs. -9.45% +/- 12.07%; P = 0.006). IGF-I SD score
      increased less with LD than CD for 0 to 3 and 0 to 6 months, although for IGF
      binding protein-3 SD score, there was no significant difference between doses at
      any time. Arthralgia was the only adverse event that occurred significantly less
      frequently with LD than with CD. Calculated changes based on gender and onset
      indicated greater changes in males than females for body composition, but there
      was little difference in GH-related adverse events between males and females. The
      lower starting dose with dose titration appeared more favorable, but differences
      in response between genders and onset of GH deficiency need to be taken into
      account when setting an individual dose regimen.

PMID- 11994328
TI  - The ectopic expression of the gastric inhibitory polypeptide receptor is frequent
      in adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia,
      but rare in unilateral tumors.
AB  - Control of cortisol secretion by the abnormal expression of the gastric
      inhibitory polypeptide receptor (GIP-R) have been observed in some rare cases of
      ACTH-independent, food-dependent Cushing's syndrome (FD-ACS) due to adrenal
      adenoma (AA) or bilateral macronodular hyperplasia (AIMAH). This study was
      performed to determine the prevalence of GIP-R ectopic expression in ACS and its
      correlation with fasting cortisol levels. GIP-R expression was studied by RT-PCR
      in 30 unilateral adrenal tumors [16 AA and 14 adrenocortical cancer (AC)] and 8
      AIMAH tissues. Fasting and postprandial cortisol levels were assayed,
      respectively, at 0800 and 1200 h in AA, AC, and AIMAH, and 1 h after a morning
      standard meal in 6 AIMAH patients. Similar expression of 2 GIP-R isoforms was
      observed in 1 of 16 AA, 0 of 14 AC, and 4 of 8 AIMAH as well as in the 4
      insulinomas used as positive controls. In vitro study of the GIP-R-expressing AA
      showed stimulation of cortisol secretion and cAMP production by GIP. The fasting
      0800-h plasma cortisol level was above 276 nmol/liter in all patients except 1 AA
      case and 1 AIMAH case, both of whom expressed GIP-R. In the 3 additional AIMAH
      cases that expressed the GIP-R, fasting plasma cortisol levels were above 276
      nmol/liter. This study demonstrates that ectopic expression of GIP-R is rare in
      AA and is usually associated with the low fasting plasma cortisol levels that
      characterize FD-ACS. In contrast, GIP-R expression is frequent in AIMAH and might
      not always be associated with a low fasting plasma cortisol level. This suggests
      that maintenance of hypercortisolemia in GIP-R- expressing AIMAH does not always
      depend solely on GIP-R, and that simultaneous abnormal expression of other
      membrane receptors might be present. The expression of GIP-R could not be
      observed during malignant transformation of the adrenal cortex. This study
      highlighted the major role of cAMP alterations secondary to GIP-R ectopic
      expression in the pathophysiology of AIMAH and in some rare cases of well
      differentiated benign adrenocortical tumors.

PMID- 11994329
TI  - Hypersecretion of FSH in infant boys and girls born small for gestational age.
AB  - Prenatal growth restraint, as reflected in a low birthweight for gestational age,
      is a risk factor for postpubertal FSH hypersecretion and for reduced gonadal
      size. The ontogeny of the low-birthweight effect on the FSH-inhibin B feedback
      loop is unknown. Infancy is an episode of choice to study the possibility of an
      early low-birthweight effect on the FSH-inhibin B loop because this phase is
      characterized by high activity within the gonadal axis. We assessed serum
      concentrations of FSH and inhibin B in 46 infants [26 girls and 20 boys; mean
      age, 4 months; range, 3-6 months; 17 appropriate for gestational age (AGA), 29
      small for gestational age (SGA); mean birthweight, 3.2 kg for AGA vs. 2.3 kg for
      SGA], together with circulating levels of LH, E2, and free androgen index. In SGA
      girls and boys, serum FSH levels were 2- and 4-fold higher (P < 0.001),
      respectively, than in AGA controls of the same gender (7.3 +/- 0.9 vs. 3.8 +/-
      0.4 IU/ml and 2.9 +/- 0.5 vs. 0.7 +/- 0.2 IU/ml). Serum LH, inhibin B, and free
      androgen index/E2 concentrations were similar in AGA and SGA infants. In
      conclusion, prenatal growth restraint was found to be followed by elevated serum
      FSH concentrations in infant girls and boys. SGA infants seem to need an
      augmented FSH drive to fulfill inhibin B requirements on the afferent side of the
      feedback loop. The late-endocrine correlates of early growth restraint are
      herewith extended to include the main axis of reproduction in both genders. It
      remains to be studied whether FSH hypersecretion in infancy is a marker of
      subsequent subfertility.

PMID- 11994330
TI  - The effects of short-term administration of two low doses versus the standard GH
      replacement dose on insulin sensitivity and fasting glucose levels in young
      healthy adults.
AB  - GH has both diabetogenic and insulin-like actions. Supraphysiological GH doses
      are known to reduce insulin sensitivity (S(I)), but lower doses are less well
      studied. We therefore compared the effects of two physiological GH doses
      (intermediate, 0.0033 mg/kg x d; low, 0.0017 mg/kg x d) with the standard adult
      GH deficiency replacement dose (standard, 0.008 mg/kg x d) on S(I), beta-cell
      function, IGF-I, and IGF binding proteins (IGFBPs)-1 and -3 in healthy adults.
      Eleven healthy nonobese volunteers (4 males and 7 females, aged 21-38 yr)
      received 7 daily injections of the standard and intermediate GH doses, and 10 (5
      males and 5 females, aged 21-38 yr) received the low dose. Fasting blood samples
      were collected daily (days 1-8). S(I) and beta-cell function were calculated
      using the Homeostasis model assessment. All GH doses increased IGF-I and IGFBP-3
      levels, with the standard dose inducing the greatest rise (P < 0.001). At day 2
      vs. baseline, all three doses increased the IGF-I/IGFBP-3 ratio, but only the
      standard dose lowered IGFBP-1 levels (P = 0.03). The standard dose reduced S(I)
      (P = 0.01), whereas the intermediate dose increased S(I) (P < 0.005) and lowered
      fasting insulin levels (P < 0.01). The low dose did not modify S(I), but reduced
      fasting glucose levels (P < 0.0001) and increased beta-cell function (P = 0.001).
      Males demonstrated higher IGF-I and IGFBP-3 responsiveness to the standard dose
      than females. Males also showed greater increase in S(I) and decrease in fasting
      glucose levels on both intermediate and low doses. In conclusion, the metabolic
      effects of GH are dose- and gender-dependent. The standard adult GH deficiency
      replacement dose induced insulin resistance, whereas lower doses improved S(I),
      especially in males. The low GH dose lowered fasting glucose levels and could
      represent the optimal dose to stimulate beta-cell function without compromising
      S(I) in insulin-resistant GH-deficient adults.

PMID- 11994331
TI  - The role of thyroid hormone in blood pressure homeostasis: evidence from short
      term hypothyroidism in humans.
AB  - Arterial hypertension is known to be frequently associated with thyroid
      dysfunction, with a particularly high prevalence in chronic hypothyroidism.
      However, to our knowledge no comprehensive study addressed causal mechanisms
      possibly involved in this association. We here report the physiological
      relationships between blood pressure and neuro-humoral modifications induced by
      acute hypothyroidism in normotensive subjects. Twelve normotensive patients with
      previous total thyroidectomy were studied. Ambulatory 24-h blood pressure
      monitoring was performed, and free T(3), free T(4), TSH, PRA, aldosterone,
      cortisol, adrenaline, and noradrenaline were assayed 6 wk after oral L-T(4)
      withdrawal (phase 1) and 2 months after resumption of treatment (phase 2). During
      the hypothyroid state (TSH, 68.1 +/- 27.7 microIU/ml; mean +/- SD), daytime
      arterial systolic levels slightly, but significantly, increased (125.5 +/- 9.7
      vs. 120.4 +/- 10.8 mm Hg; P < 0.05), and daytime diastolic levels (84.6 +/- 7.9
      vs. 76.4 +/- 6.8 mm Hg; P < 0.001), noradrenaline (2954 +/- 1578 vs. 1574 +/- 962
      pmol/liter; P < 0.001), and adrenaline (228.4 +/- 160 vs. 111.3 +/- 46.1
      pmol/liter; P < 0.05) also increased. PRA remained unchanged (0.49 +/- 0.37 vs.
      0.35 +/- 0.21 ng/ml.h; P = NS), whereas both aldosterone (310.3 +/- 151 vs. 156.9
      +/- 67.5 pmol/liter; P < 0.005) and cortisol (409.2 +/- 239 vs. 250.9 +/- 113
      pmol/liter; P < 0.02) significantly increased. By using univariate logistic
      regression daytime arterial diastolic values, noradrenaline and aldosterone were
      found to be significantly related to the hypothyroid state (P < 0.02, P < 0.036,
      and P < 0.024, respectively). In conclusion, our data show that thyroid hormones
      participate in the control of systemic arterial blood pressure homeostasis in
      normotensive subjects. The observed sympathetic and adrenal activation in
      hypothyroidism, which is reversible with thyroid hormone treatment, may also
      contribute to the development of arterial hypertension in human hypothyroidism.

PMID- 11994332
TI  - Does birth weight predict adult serum cortisol concentrations? Twenty-four-hour
      profiles in the United kingdom 1920-1930 Hertfordshire Birth Cohort.
AB  - Low birth weight and weight in infancy are associated with adult insulin
      resistance and type 2 diabetes. A proposed mechanism is programming of the
      hypothalamic-pituitary-adrenal axis by intrauterine undernutrition, leading to
      persistently elevated cortisol concentrations. We examined 24-h serum cortisol
      profiles (samples every 20 min) in 83 healthy elderly men and women whose birth
      weight and infant weight were recorded. Variables derived from these profiles
      included trough, peak, and area under the curve concentrations; the time of
      onset, rate of rise, duration, and peak of the early morning cortisol rise;
      postprandial secretion; and regularity of secretion (approximate entropy). None
      of these parameters was related to birth weight, weight at 1 yr, or change in
      weight SD score between birth and 1 yr. Consistent with other studies, 0730-0900
      h cortisol concentrations were higher in men and women of lower birth weight,
      although this was not statistically significant (P = 0.08). Our findings do not
      support the hypothesis that reduced intrauterine and infant growth are associated
      with continuously raised cortisol concentrations in old age. Programmed effects
      on the hypothalamic-pituitary-adrenal axis may influence reactivity rather than
      resting secretion.

PMID- 11994333
TI  - Potassium citrate prevents increased urine calcium excretion and bone resorption
      induced by a high sodium chloride diet.
AB  - The amount of sodium chloride in the diet of industrialized nations far exceeds
      physiological requirements. The impact of abundant dietary salt on skeletal
      health has yet to be established, but is potentially detrimental through
      increased urinary calcium losses. We examined the effect of increased dietary
      sodium chloride on urine calcium excretion and bone turnover markers in
      postmenopausal women and, further, whether potassium citrate attenuates the
      effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to
      a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225
      mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus
      placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum
      osteocalcin, and fasting serum PTH were measured at the end of the low- and high
      salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12
      mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium
      citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N
      telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per
      millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7
      nanomoles bone collagen equivalents per millimole creatinine in the high salt
      plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t
      test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of
      oral potassium citrate to a high-salt diet prevented the increased excretion of
      urine calcium and the bone resorption marker caused by a high salt intake.
      Increased intake of dietary sources of potassium alkaline salts, namely fruit and
      vegetables, may be beneficial for postmenopausal women at risk for osteoporosis,
      particularly those consuming a diet generous in sodium chloride.

PMID- 11994334
TI  - Menstrual cycle irregularity and risk for future cardiovascular disease.
AB  - Cross-sectional studies suggest that women who have irregular menstrual cycles
      and hyperandrogenism may be at increased risk for cardiovascular disease (CVD).
      However, prospective data are lacking on the relationship between menstrual cycle
      irregularity and subsequent CVD risk. The objective of this study was to assess
      prospectively the risk for coronary heart disease (CHD) and stroke associated
      with a history of irregular menstrual cycles. The study design was a prospective
      cohort study of 82,439 female nurses who provided information in 1982 on prior
      menstrual regularity (at ages 20-35 yr) and were followed through 1996 for
      cardiovascular events. Incident reports of nonfatal myocardial infarction, fatal
      CHD, and nonfatal and fatal stroke were made. Medical records were reviewed for
      confirmation. During 14 yr (1,155,915 person-yr) of follow-up, there were 1417
      incident cases of CHD and 838 incident cases of stroke, including 471 cases of
      ischemic stroke. Compared with women reporting a history of very regular
      menstrual cycles, women reporting usually irregular or very irregular cycles had
      an increased risk for nonfatal or fatal CHD [age-adjusted relative risks (RR),
      1.25 and 1.67, respectively; 95% confidence intervals (CI), 1.07-1.47 and 1.35
      2.06, respectively]. Increased risks for CHD associated with prior cycle
      irregularity remained significant after adjustment for body mass index and
      several potential confounders. There was a nonsignificant increase in overall
      stroke risk (RR, 1.30; 95% CI = 0.97-1.74) and in ischemic stroke risk (RR, 1.40;
      95% CI = 0.97-2.04) associated with very irregular cycles. Menstrual cycle
      irregularity may be a marker of metabolic abnormalities predisposing to increased
      risk for CVD.

PMID- 11994335
TI  - Familial isolated growth hormone deficiency is associated with increased systolic
      blood pressure, central obesity, and dyslipidemia.
AB  - To assess the metabolic and cardiovascular consequences of GH deficiency (GHD) on
      cardiovascular risk factors, we studied a homogeneous population with GHD due to
      a homozygous defect in the GHRH receptor gene. Anthropometric, metabolic, and
      cardiovascular measurements (at rest, during treadmill exercise, and during
      orthostatic stress) and echocardiographic data were obtained from 16 GH-naive, GH
      deficient (GHD) adults and 31 age-, sex-, and body mass index-matched control
      (CO) subjects. The percentage of fat mass, waist to hip ratio, and total and low
      density lipoprotein cholesterol were higher in the GHD group. However, high
      density lipoprotein cholesterol, triglyceride, and fasting glucose levels were
      similar between groups, and fasting insulin and homeostasis model assessment of
      insulin resistance (HOMA(IR)) were lower in the GHD group. Systolic blood
      pressure (SBP) was higher in the GHD group, but no difference in diastolic blood
      pressure or heart rate (HR) existed. Blood pressure and HR responses to exercise
      did not differ between groups. During passive orthostatic stress the decrease in
      SBP was higher in the GHD than in the CO group, whereas an increase in diastolic
      blood pressure was not observed in the GHD group. Moreover, the increase in HR
      was blunted in the GHD compared with the CO group. Left ventricular mass and mass
      index were lower in the GHD group. In conclusion, this genetically homogeneous
      isolated GHD population presents a syndrome characterized by central obesity,
      dyslipidemia, and elevated SBP but reduced cardiac dimensions compared with
      controls.

PMID- 11994336
TI  - Seasonal changes in calciotropic hormones, bone markers, and bone mineral density
      in elderly women.
AB  - Seasonal variation of serum vitamin D metabolites, PTH, bone turnover markers,
      and bone mineral density (BMD), adjusted for confounding variables, was studied
      in a cross-sectional population of 251 ambulatory elderly women aged 65-77 yr. A
      significant (P < 0.05) seasonal change was observed in serum 25 hydroxyvitamin D
      (25OHD), bone resorption marker (urine N-telopeptide), and BMD of the spine,
      total body, and mid-radius. Serum 25OHD was significantly lower (P < 0.05) in
      winter (December, January, February, March) compared with summer (June, July,
      August, September), with the nadir in February (68.4 +/- 6.74 nmol/liter) and the
      zenith in August (85.6 +/- 5.12 nmol/liter). Mean serum PTH levels were higher in
      winter when serum 25OHD was low, and mean serum PTH was lower in summer when
      serum 25OHD was high, although the seasonal change in serum PTH was not
      significant. The change in serum 1,25-dihydroxy vitamin D(3) paralleled that of
      serum 25OHD levels, but the seasonal effect was not significant. Mean 24-h urine
      N-telopeptide showed a significant seasonal change (P < 0.05); it was about 24%
      higher in February (zenith) compared with that in August (nadir). The zenith
      month of urine N-telopeptide levels corresponded to the nadir month of serum
      25OHD levels and vice versa. A significant (P < 0.05) inverse correlation was
      observed between 24-h urine N-telopeptides and serum 25OHD levels. There was a
      significant (P < 0.05) seasonal change in mean BMD of spine, total body, and mid
      radius. These changes paralleled those in serum 25OHD levels. Spine BMD was 8.4%
      higher in August (zenith) compared with that in February (nadir), whereas total
      body BMD and mid-radius BMD were 6.1 and 7.6% higher, respectively, in July
      (zenith) compared with that in January (nadir). There was a nonsignificant
      increase of 3.6% in total hip BMD. In summary (see Fig. 5), the seasonal changes
      in vitamin D metabolism in elderly women are closely associated with small
      changes in serum PTH, changes in bone resorption, and BMD.

PMID- 11994337
TI  - Growth hormone and low dose estrogen in Turner syndrome: results of a United
      States multi-center trial to near-final height.
AB  - A cardinal clinical feature of Turner syndrome (TS) is linear growth failure
      resulting in extreme short stature: the median adult height of untreated women
      with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In
      the largest multicenter, randomized, long-term, dose-response study conducted in
      the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of
      recombinant human GH with either low dose ethinyl E2 or oral placebo. The study
      was placebo-controlled for both GH and estrogen for the first 18 months and
      remained placebo-controlled for estrogen for its duration. The near-final height
      of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after
      5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an
      average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was
      greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5%
      of untreated patients. Mean near-final heights of subjects who received the lower
      GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm,
      respectively; those who received the higher GH dose with or without estrogen
      achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm,
      respectively. Factors that most impacted outcome were younger age, lower bone
      age/chronological age ratio, lower body weight, and greater height SD score at
      study entry. This study demonstrates significant GH-induced improvement in height
      SD score, with correction of height to within the normal channels for a
      significant number of patients, and provides evidence of a GH dose-response
      effect. These data also indicate that early administration of estrogen, even at
      relatively low doses, does not improve gain in near-final height in patients with
      TS.

PMID- 11994338
TI  - Recombinant human GH replacement therapy and thyroid function in a large group of
      adult GH-deficient patients: when does L-T(4) therapy become mandatory?
AB  - The effect on thyroid function of GH administration to 66 adult patients with
      severe GH deficiency was studied. Seventeen patients were euthyroid, and 49 had
      central hypothyroidism and were adequately treated with L-T(4). Forty patients
      were assigned to a low recombinant human GH (rhGH) regimen (3 microg/kg body wt.d
      for 3 months followed by 6 microg/kg body wt.d for another 3 months) and 26 to a
      higher one (6 microg/kg body wt.d for 3 months followed by 12 microg/kg body wt.d
      for another 3 months). Serum IGF-I, TSH, free T(4) (FT(4)), free T(3) (FT(3)),
      reverse T(3), T(4)-binding globulin, and antithyroid autoantibody (TgAb and
      TPOAb) were measured in basal condition and after 3 and 6 months of therapy.
      Normalization of IGF-I levels was obtained after 6-month rhGH treatment in 67% of
      patients, independently from the dose, whereas a significant reduction in FT(4)
      and reverse T(3) levels was recorded (P < 0.01), without variations in all the
      other parameters studied, including serum TSH, FT(3), and T(4)-binding globulin
      circulating levels. Antithyroid autoantibodies were detected in 11 of 66 patients
      (16.6%). Eight of 17 (47%) euthyroid subjects and 9 of 49 (18.3%) central
      hypothyroid patients, despite adequate substitution at baseline, showed FT(4)
      levels under the normal range at the end of the study. Altogether, 17 of 66
      patients (25.7%) worsened their thyroid function. This study shows that GH
      deficiency masks in a consistent number of adult patients a state of central
      hypothyroidism. Therefore, during rhGH treatment, a careful monitoring of thyroid
      function is mandatory to start or adjust L-T(4) substitutive therapy.

PMID- 11994339
TI  - Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen
      deficient women: a placebo-controlled trial.
AB  - Thirty-eight women, aged 25-65 yr, with androgen deficiency due to
      hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if
      <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized,
      placebo-controlled, double blind study, followed by a 6-month open treatment
      period. The administration of DHEA raised the serum levels of DHEAS to normal age
      related reference ranges and increased androstenedione and T to subnormal levels.
      Androgen effects on skin and/or pubic and/or axillary hair were observed in 84%
      (32 of 38) of the women after all received 6 months of DHEA treatment. No such
      effects were observed after the placebo treatment. These effects after 6 months
      were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03),
      androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages
      of partners who reported improved alertness, stamina, and initiative by their
      spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and
      11%, respectively, in the placebo group (P < 0.05). According to the partners,
      sexual relations tended to improve compared with placebo (P = 0.06). After 6
      months of treatment, increased sexual interest or activity was reported by 50% of
      the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking
      placebo (P = NS). Compared with levels after placebo administration, high density
      lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum
      concentrations of IGF-I, serum markers of bone metabolism, and bone density did
      not change. In conclusion, oral administration of a low dose of DHEA to adult
      hypopituitary women induced androgen effects on skin and axillary and pubic hair
      as well as changes in behavior, with only minor effects on metabolism.

PMID- 11994340
TI  - Genetic and environmental factors affect bone density variances of families of
      men and women with osteoporosis.
AB  - Our aim was to assess the relative impacts of genetics and environment in the
      families of osteoporotic patients and identify the best subgroup of patients to
      investigate the genes associated with osteoporosis. We recruited 36 men and 47
      women with osteoporosis (probands), median age of 52 and 68 yr, and all their
      siblings (90) and offspring (83). The families were classified as young or old on
      the basis of the median age of the probands. We measured the bone mineral density
      at the femoral neck (FN) and lumbar spine (LS) adjusted for age and weight and
      standardized (Z-score). Physical activity, nutritional calcium, and alcohol and
      tobacco consumption were investigated. We compared the mean Z-score using linear
      mixed model and assessed the familial resemblance using intraclass correlation.
      The mean Z-scores of the families of osteoporotic patients were significantly
      negative at FN and LS, with no intergeneration or intergender differences. At FN,
      but not at LS, the mean Z-score was independently lower in the families of male
      probands (mean +/- SD: -0.57 +/- 0.96, female: -0.18 +/- 0.85, P = 0.012) and in
      young families (-0.58 +/- 0.94, old families: -0.11 +/- 0.83, P = 0.006). This
      suggested that the lower Z-score in the families of men with osteoporosis was
      related to their younger age. There was significant phenotypic resemblance among
      members in the families. In the families of female probands, the correlation
      between the probands and her siblings was weak and disappeared after adjustment
      on environment, and a resemblance appeared within their children (FN: r = 0.61)
      suggesting that different environment had masked the resemblance in this
      subgroup. In the families of male probands, a strong resemblance persisted after
      adjusting for environment, (proband-offspring at FN: r = 0.46 and within
      offspring at FN: r = 0.66, at LS: r = 0.61). This showed that resemblance was
      independent of a common measurable environment in these families of men with
      osteoporosis. In conclusion, mainly young osteoporotic patients, most of whom
      were male in our study, are affected by the genetic component.

PMID- 11994341
TI  - Strontium ranelate: dose-dependent effects in established postmenopausal
      vertebral osteoporosis--a 2-year randomized placebo controlled trial.
AB  - The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS)
      trial was to investigate the efficacy and safety of different doses of SR, a
      novel agent in the treatment of postmenopausal osteoporosis. A randomized,
      multicenter, double-blind, placebo-controlled trial was undertaken in 353
      osteoporotic women with at least one previous vertebral fracture and a lumbar T
      score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d
      for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD),
      assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included
      femoral BMD, incidence of new vertebral deformities, and biochemical markers of
      bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a
      dose-dependent manner in the intention-to-treat population: mean annual slope
      increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was
      significantly higher than placebo (P < 0.01). There was a significant reduction
      in the number of patients experiencing new vertebral deformities in the second
      year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval
      (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum
      levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N
      telopeptide, a marker of bone resorption, was lower with SR than with placebo.
      All tested doses were well tolerated; the 2 g/d dose was considered to offer the
      best combination of efficacy and safety. In conclusion, SR therapy increased
      vertebral BMD and reduced the incidence of vertebral fractures.

PMID- 11994342
TI  - Sensitivity and specificity of six tests for the diagnosis of adult GH
      deficiency.
AB  - Although the use of the insulin tolerance test (ITT) for the diagnosis of adult
      GH deficiency is well established, diagnostic peak GH cut-points for other
      commonly used GH stimulation tests are less clearly established. Despite that
      fact, the majority of patients in the United States who are evaluated for GH
      deficiency do not undergo insulin tolerance testing. The aim of this study was to
      evaluate the relative utility of six different methods of testing for adult GH
      deficiency currently used in practice in the United States and to develop
      diagnostic cut-points for each of these tests. Thirty-nine patients (26 male, 13
      female) with adult-onset hypothalamic-pituitary disease and multiple pituitary
      hormone deficiencies were studied in comparison with age-, sex-, estrogen status
      , and body mass index-matched control subjects (n = 34; 20 male, 14 female). A
      third group of patients (n = 21) with adult-onset hypothalamic-pituitary disease
      and no more than one additional pituitary hormone deficiency was also studied.
      The primary end-point was peak serum GH response to five GH stimulation tests
      administered in random order at five separate visits: ITT, arginine (ARG),
      levodopa (L-DOPA), ARG plus L-DOPA, and ARG plus GHRH. Serum IGF-I concentrations
      were also measured on two occasions. For purposes of analysis, patients with
      multiple pituitary hormone deficiencies were assumed to be GH deficient. Three
      diagnostic cut-points were calculated for each test to provide optimal separation
      of multiple pituitary hormone deficient and control subjects according to three
      criteria: 1) to minimize misclassification of control subjects and deficient
      patients (balance between high sensitivity and high specificity); 2) to provide
      95% sensitivity for GH deficiency; and 3) to provide 95% specificity for GH
      deficiency. The greatest diagnostic accuracy occurred with the ITT and the ARG
      plus GHRH test, although patients preferred the latter (P = 0.001). Using peak
      serum GH cut-points of 5.1 microg/liter for the ITT and 4.1 microg/liter for the
      ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity
      (92 and 91%, respectively) for GH deficiency were achieved. To obtain 95%
      specificity, the peak serum GH cut-points were lower at 3.3 microg/liter and 1.5
      microg/liter for the ITT and ARG plus GHRH test, respectively. There was
      substantial overlap between patients and control subjects for the ARG plus L
      DOPA, ARG, and L-DOPA tests, but test-specific cut-points could be defined for
      all three tests to provide 95% sensitivity for GH deficiency (peak GH cut-points:
      1.5, 1.4 and 0.64 microg/liter, respectively). However, 95% specificity could be
      achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut
      points (0.25 and 0.21 microg/liter, respectively) and not at all with the L-DOPA
      test. Although serum IGF-I levels provided less diagnostic discrimination than
      all five GH stimulation tests, a value below 77.2 microg/liter was 95% specific
      for GH deficiency. In conclusion, the diagnosis of adult GH deficiency can be
      made without performing an ITT, provided that test-specific cut-points are used.
      The ARG plus GHRH test represents an excellent alternative to the ITT for the
      diagnosis of GH deficiency in adults.

PMID- 11994344
TI  - FFAs and QT intervals in obese women with visceral adiposity: effects of
      sustained weight loss over 1 year.
AB  - We evaluated 66 obese patients grouped by waist-to-hip ratio (WHR) into group A
      (WHR > 0.85, n = 30) and group B (WHR < or = 0.85, n = 36), before and after 1 yr
      of diet-induced weight loss compared with 25 nonobese women. Before diet, the
      longest values of QT intervals and the highest levels of FFA and catecholamines
      were in group A (P < 0.01). In obese women (both groups), the corrected QT (QTc);
      interval correlated with plasma FFA (P < 0.01) and catecholamine (P < 0.02)
      concentrations. After 1 yr of diet, at the same levels of body weight reduction,
      the decrement of the QTc interval (P < 0.02), FFA (P < 0.01) and catecholamine (P
      < 0.02) levels were significantly greater in-group A than group B. In
      multivariate analysis, the decline of the QTc interval after weight loss was
      associated with changes in plasma FFA independently of changes in WHR and plasma
      catecholamines. Our data suggest that the QTc interval is tightly correlated with
      plasma FFA levels; shortening of cardiac repolarization times in the course of
      long-lasting weight reduction may reduce the risk of ventricular electrical
      instability, especially in women with abdominal adiposity.

PMID- 11994345
TI  - Adipose tissue IL-6 content correlates with resistance to insulin activation of
      glucose uptake both in vivo and in vitro.
AB  - Obesity and type 2 diabetes are associated with insulin resistance, the
      mechanisms of which remain poorly understood. A significant correlation between
      circulating IL-6 level and insulin sensitivity has recently been found in humans.
      Because adipose tissue could be a significant source of IL-6, we analyzed the
      relationship between the levels of adipose tissue IL-6 and insulin action in
      vivo, during a hyperinsulinemic normoglycemic clamp, and in vitro by measuring
      glucose transport in adipocytes from 12 obese subjects with (n = 7) or without (n
      = 5) diabetes. We observed an inverse correlation between adipose tissue IL-6
      content and maximal insulin-responsiveness measured in vivo (P < 0.02) and in
      vitro (P < 0.02). Conversely, there was no significant correlation between these
      two later parameters and adipose tissue leptin or tumor necrosis factor-alpha
      protein contents. Furthermore, we showed, for the first time, the presence of
      immunoreactive IL-6 receptors in the plasma membrane of human abdominal sc
      adipocytes. This suggests that locally secreted IL-6 could act on adipocytes by
      an autocrine/paracrine mechanism. In conclusion, increased IL-6 production by sc
      adipose cells might participate to the insulin-resistant state observed in human
      obesity.

PMID- 11994346
TI  - Gonadotropin-suppressive therapy in girls with early and fast puberty affects the
      pace of puberty but not total pubertal growth or final height.
AB  - Early and fast puberty (EFP) in girls, defined as pubertal onset at age 8-9 yr,
      with an accelerated course, may cause compromised final height (FHt) and
      psychosocial distress. Treatment with a gonadotropin-suppressive agent is
      controversial, because the improvement in FHt is equivocal and there may be risk
      of obesity. We analyzed the data of 126 girls with EFP: 63 treated with GnRH
      analog (GnRHA) since Tanner stage 3, for 2-4 yr; and 63 untreated. Age at onset
      of puberty; accelerated time of transition from Tanner stage 2 to 3 (<1.3 yr);
      and clinical, hormonal and sonographic findings were similar in the 2 groups. The
      girls given GnRHA treatment had a significantly prolonged pubertal course,
      compared with the accelerated course in the untreated girls (4.7 +/- 0.4 vs. 2.45
      +/- 0.4 yr, P < 0.001). After therapy, they reached Tanner stages 4 and 5 and FHt
      at a significantly older age than the untreated group (P < 0.001), and their
      menarche was delayed (12.8 +/- 0.6 vs. 10.8 +/- 0.5 yr, P < 0.001). However, the
      different pace of puberty in the 2 groups did not change the total pubertal
      growth and the bone maturation rate. The Ht gain from Tanner stage 3 to 4 (10.4
      +/- 2.7 vs. 11.2 +/- 3.1 cm) and from Tanner stage 4 to FHt (8.2 +/- 2.7 vs. 8.8
      +/- 3.6 cm) was similar in the treated and untreated girls, as were absolute Ht
      and bone age at each pubertal stage. The weight gain of the treated girls was
      more pronounced during treatment (P = 0.0016), but it was arrested after
      discontinuation of therapy; and by the time FHt was reached, the body mass index
      was similar in the 2 groups. The treated and untreated girls achieved a similar
      mean FHt, which was not significantly different from their respective mean target
      Ht (THt). Individual analysis revealed that 70% of the treated girls and 67% of
      the untreated girls attained their THt range (THt +/- 0.5 SD) or surpassed it. In
      conclusion, treatment with GnRHA affected only the pace of EFP. The similar Ht
      gain and bone maturation rate at each pubertal stage in the treated and untreated
      girls may suggest that the total pubertal growth is not dependent on pubertal
      duration and pace and is probably determined already at the onset of the normal
      pubertal development. The treatment did not compromise the FHt and did not cause
      long-lasting obesity. Therefore, GnRHA therapy may be suggested for use in girls
      who have psychosocial difficulties in coping with EFP.

PMID- 11994347
TI  - The impact of cranial irradiation on GH responsiveness to GHRH plus GH-releasing
      peptide-6.
AB  - Patients treated with cranial radiation are at risk of GH deficiency (GHD). We
      evaluated somatotroph responsiveness to maximal provocative tests exploring the
      GH releasable pool in relation to the impact of radiation damage to the
      hypothalamic-pituitary unit. The GH-releasing effect of GHRH plus GH secretagogue
      [GH-releasing peptide (GHRP)-6] (GHRH+GHRP-6) was studied in 22 adult patients
      (age, 23.2 +/- 1.4 yr; 8 female and 14 male; mean body mass index, 22.6 +/- 0.7
      kg/m(2)) who received cranial radiation for primary brain tumor distant from
      hypothalamic-pituitary region 7.6 +/- 0.7 yr before GH testing. Two stimulatory
      tests for GH secretion were employed: insulin tolerance test (ITT, 0.15 IU/kg
      regular insulin i.v. bolus); and GHRH+GHRP-6 test: GHRH (Geref Serono, Madrid,
      Spain; l microg/kg) plus GHRP-6 (CLINALFA, Laufelingen, Switzerland; 1 microg/kg)
      as i.v. bolus. Serum GH was measured (Delphia; Perkin Elmer, Wallac, Turku,
      Finland) at -30, -15, 0, 15, 30, 45, 60, 90, and 120 min. Anterior pituitary
      function was normal in all except in 1 female with hyperprolactinemia. Twelve out
      of 22 irradiated patients were GH-deficient (GHD) with both tests. Eleven out of
      22 (50%) irradiated patients were severely GHD, according to the ITT (GH < 3
      microg/liter; mean GH peak, 1.5 +/- 0.5 microg/liter). In 9 irradiated patients,
      in whom ITT was performed as well, mean peak GH after the GHRH+GHRP-6 test was
      6.2 +/- 0.8 microg/liter, which is considered as severe GHD, according to our own
      cut-off for the test (peak GH < 10 microg/liter). GH responses to both tests were
      highly concordant, but the differential in the GH peak concentrations between GHD
      and non-GHD irradiated patients was significantly larger for the GHRH+GHRP-6 test
      than that for the ITT. The 2 discordant responses, i.e. poor response to the ITT
      and good response to the GHRH+GHRP-6 test, were found in 1 hyperprolactinemic
      female patient and in 1 other female. One irradiated patient was diagnosed as GHD
      only with the combined test, because ITT was contraindicated because of epilepsy.
      PRL and cortisol responses to ITT were normal in all irradiated patients and did
      not depend on the GH status. IGF-I levels were not informative or discriminative
      between the GHD and non-GHD irradiated adult patients. In conclusion, the use of
      GH secretagogues plus GHRH is an easy, reliable and accurate way of assessing GH
      secretion in cranially irradiated patients. Impairment of the GH releasable pool
      in the irradiated patients, with a maximal provocative test, reflects alterations
      in the hypothalamic-pituitary unit caused by radiotherapy.

PMID- 11994348
TI  - Effects of testosterone replacement and/or resistance exercise on the composition
      of megestrol acetate stimulated weight gain in elderly men: a randomized
      controlled trial.
AB  - Megestrol acetate (MA) (Bristol-Myers Squibb Co., Princeton, NJ) increases weight
      gain in AIDS and cancer patients and in age-related cachexia; however, the weight
      gain is predominately fat. We determined if adding resistance exercise and/or
      testosterone (T) replacement to MA administration would result in a more
      favorable body composition change than MA alone. Thirty older men (aged 67.0 +/-
      5.8) completed this 12-wk study. All subjects received MA and were randomly
      assigned to one of the following groups: placebo (P) injections, resistance
      training (RT) and P (RT + P), weekly injections of T (100 mg/wk) or, RT and T (RT
      + T). The mean increase in body weight for all groups combined was 3.8 kg (P <
      0.0001), but this increase was not different between groups. There was a
      significant interaction for the change in thigh muscle cross-sectional area (P =
      0.0006). Thigh muscle cross-sectional area was significantly reduced from
      baseline by 5.20 [1.62] cm(2) (P = 0.05) in P which was not prevented in T [-4.44
      (1.66) cm(2) from baseline; P = 0.04]. RT prevented this decline [+0.61 (1.41)
      cm(2) from baseline]. Muscle cross-sectional area increased 4.51 (1.69) cm(2)
      from baseline in RT + T (P = 0.002 vs. P and P = 0.002 vs. T). Despite
      significant weight gain, MA appears to have an antianabolic effect on muscle size
      even when combined with T replacement. Resistance exercise attenuated this
      reduction in muscle mass and when combined with T had an anabolic effect on
      muscle mass.

PMID- 11994349
TI  - Twenty-one day administration of dienogest reversibly suppresses gonadotropins
      and testosterone in normal men.
AB  - Androgen-progestin combinations are promising male contraceptive regimens.
      Optimization of these regimens includes the development of new progestins with
      more favorable biological properties. In this context we tested the effects of
      the progestin dienogest (DNG) on reproductive hormones and metabolic parameters
      in men. After a 3-wk control period, 25 men were randomly assigned to receive
      daily doses of 2, 5, or 10 mg DNG or placebo and 10 mg cyproterone acetate for 21
      d (n = 5 subjects/group). Subjects were followed for 2 wk after cessation of
      hormone administration. Weekly blood samples, physical examinations, hormone and
      chemistry measurements, semen analysis, and sexual/behavioral assessments were
      performed. These parameters were compared among study groups and within each
      group at different time points throughout the study periods. DNG and cyproterone
      acetate administration resulted in profound suppression of gonadotropins and T
      with no change in SHBG levels. No adverse effects were detected in any subject.
      Hormone levels returned to baseline after stopping hormone intake. DNG is a
      potent suppressor of gonadotropins and T in men and does not induce adverse
      effects over a 21-d administration. DNG is a promising progestin to be used in
      clinical trials for male contraception.

PMID- 11994350
TI  - Children with classic congenital adrenal hyperplasia have elevated serum leptin
      concentrations and insulin resistance: potential clinical implications.
AB  - Leptin is secreted by the white adipose tissue and modulates energy homeostasis.
      Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including
      the sympathetic nervous system and the adrenal medulla, have been implicated in
      the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH)
      is characterized by a defect in cortisol and aldosterone secretion, impaired
      development and function of the adrenal medulla, and adrenal hyperandrogenism. To
      examine leptin secretion in patients with classic CAH in relation to their
      adrenomedullary function and insulin and androgen secretion, we studied 18
      children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal
      children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index
      (BMI). Serum leptin concentrations were significantly higher in patients with CAH
      than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this
      difference persisted when leptin values were corrected for BMI. When compared
      with their normal counterparts, children with CAH had significantly lower plasma
      epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine
      concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting
      serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P < 0.001) and
      testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dl, P = 0.003) concentrations.
      Insulin resistance determined by the homeostasis model assessment method was
      significantly greater in children with classic CAH than in normal children (2.2
      +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly
      and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free
      metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear
      regression analysis indicated that serum leptin concentrations were best
      predicted by BMI in both patients and controls. Gender predicted serum leptin
      concentrations in controls but not in patients with classic CAH. No association
      was found between the dose of hydrocortisone and serum leptin (r = -0.17, P =
      0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our
      findings indicate that children with classic CAH have elevated fasting serum
      leptin and insulin concentrations, and insulin resistance. These most likely
      reflect differences in long-term adrenomedullary hypofunction and glucocorticoid
      therapy. Elevated leptin and insulin concentrations in patients with CAH may
      further enhance adrenal and ovarian androgen production, decrease the therapeutic
      efficacy of glucocorticoids, and contribute to later development of polycystic
      ovary syndrome and/or the metabolic syndrome and their complications.

PMID- 11994351
TI  - Effects of seven years of GH-replacement therapy on insulin sensitivity in GH
      deficient adults.
AB  - The few trials in GH-deficient (GHD) adults that have investigated the long-term
      effects of GH-replacement therapy on insulin sensitivity have shown conflicting
      results. In this study, insulin sensitivity was determined using the
      hyperinsulinemic, euglycemic clamp technique in 11 GHD adults at baseline and
      after 6 months, 1 yr, 2 yr, and 7 yr of GH-replacement therapy. Furthermore,
      insulin sensitivity in the GHD patients was compared with that in 11 matched
      control subjects at baseline and with that in 11 other matched controls at study
      end. The mean initial GH dose was 1.10 mg/d. The dose was gradually lowered; and
      after 7 yr, the mean dose was 0.61 mg/d. A sustained reduction in body fat and a
      sustained increase in fat-free mass were observed. Serum high-density lipoprotein
      cholesterol (HDL-C) increased, and serum low-density lipoprotein-cholesterol (LDL
      C) decreased, after 7 yr of treatment. Fasting blood glucose was transiently
      increased during the first year of GH replacement. The glucose infusion rate/body
      weight (GIR/BW), as measured using the hyperinsulinemic, euglycemic clamp
      technique, was unaltered during GH-replacement therapy. The comparisons with the
      control subjects revealed that GIR/BW in the GHD patients was 45% of that in the
      control subjects at baseline; whereas, at study end, the GIR/BW was 71% of that
      in the control subjects (P = 0.06 vs. baseline). This could suggest that GH
      replacement therapy may prevent the age-related decline in insulin sensitivity in
      GHD patients.

PMID- 11994352
TI  - Insulin resistance in the sisters of women with polycystic ovary syndrome:
      association with hyperandrogenemia rather than menstrual irregularity.
AB  - This study was performed to determine whether the sisters of women with
      polycystic ovary syndrome (PCOS) have evidence for insulin resistance. Three
      hundred and thirty-six women with PCOS, 307 sisters of these probands, and 47
      control women were studied. The sisters were grouped by phenotypes: PCOS
      [hyperandrogenemia (HA) with chronic oligo- or amenorrhea, n = 39], HA with
      regular menses (n = 36), unaffected (UA; n = 122), and unknown (n = 110). The
      analyses were adjusted for age and body mass index. PCOS and HA sisters of women
      with PCOS had similar and significantly elevated fasting insulin levels (P =
      0.001) as well as similar and significantly decreased fasting glucose/insulin
      ratios (P < 0.001) suggestive of insulin resistance compared with UA sisters and
      control women. Markers of insulin resistance were associated with
      hyperandrogenemia and not with menstrual irregularity. PCOS sisters also had
      decreased levels of SHBG (P = 0.02) suggestive of higher ambient insulin levels.
      PCOS sisters had increased levels of proinsulin (P = 0.04) compared with control
      women, which suggested pancreatic beta-cell dysfunction in this group of sisters.
      The magnitude of obesity also differed significantly among the groups of sisters.
      The PCOS sisters were significantly more obese than all the other groups, and the
      HA sisters were more obese than the UA sisters. We conclude that markers of
      insulin resistance are associated with hyperandrogenemia rather than menstrual
      irregularity in the sisters of women with PCOS. Menstrual irregularity may be
      related to the magnitude of insulin sensitivity or insulin secretion or to other
      factors associated with obesity.

PMID- 11994353
TI  - Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in
      the brothers of women with polycystic ovary syndrome.
AB  - There is an inherited susceptibility to polycystic ovary syndrome (PCOS). Some
      investigators have suggested that premature male-pattern balding is a male
      phenotype in PCOS families, but this remains controversial. We recently reported
      evidence for an autosomal monogenic abnormality in ovarian and adrenal
      steroidogenesis in the sisters of women with PCOS. We performed this study to
      determine whether we could identify a clinical or biochemical phenotype in the
      brothers of women with PCOS. One hundred nineteen brothers of 87 unrelated women
      with PCOS and 68 weight- and ethnicity-comparable unrelated control men were
      examined and had fasting blood samples obtained. The odds of balding (Hamilton
      score > or = V) did not differ in the brothers of PCOS women compared with
      control men. Brothers of women with PCOS had significantly elevated
      dehydroepiandrosterone sulfate (DHEAS) levels [brothers 3035 +/- 1132 ng/ml (mean
      +/- SD) vs. control men 2494 +/- 1172 ng/ml; P < 0.05]. There was a significant
      positive linear relationship between DHEAS levels in PCOS probands and their
      brothers (r = 0.35; P = 0.001). There was no significant bimodal distribution in
      DHEAS levels, and there were no significant differences in other parameters in
      brothers of PCOS women with high DHEAS levels compared with those with low DHEAS
      levels. There is familial clustering of elevated DHEAS levels in the brothers of
      women with PCOS, suggesting that this is a genetic trait. This might reflect the
      same underlying defect in steroidogenesis that we found in the sisters of women
      with PCOS. Balding was not increased in the brothers of women with PCOS. We
      conclude that there is a biochemical reproductive endocrine phenotype in men in
      PCOS families.

PMID- 11994355
TI  - Metabolic characterization of a woman homozygous for the Ser113Leu missense
      mutation in carnitine palmitoyl transferase II.
AB  - Carnitine palmitoyl transferase (CPT) II is a key enzyme in transporting FFA into
      the mitochondrial matrix for beta oxidation. The clinical manifestation of CPT II
      deficiency is characterized mainly by myopathic symptoms. Conceivably, the
      inability of skeletal muscle to oxidize (long-chain) FFAs could also have far
      reaching metabolic consequences, such as insulin resistance secondary to
      increased muscle lipids, about which relatively little is known. We therefore
      performed a series of metabolic studies in a 43-yr-old woman homozygous for the
      Ser113Leu mutation in the CPT II gene, the single most common genetic cause of
      CPT II deficiency, and compared the results with data from a male and female
      control group taken from the Tubingen family study database. The metabolic
      studies included oral glucose tolerance test (OGTT), euglycemic hyperinsulinemic
      clamp to measure insulin sensitivity, indirect calorimetry to measure substrate
      oxidation, stable isotopes for determination of glycerol turnover, and magnetic
      resonance spectroscopy for measurement of intramyocellular lipids. Compared with
      the female control group, the patient was normal glucose tolerant but severely
      insulin resistant, basal lipolysis was markedly reduced, and carbohydrate
      oxidation was maximally increased in the basal state and did not increase further
      during insulin stimulation. Conversely, lipid oxidation was virtually absent and
      did not decrease during insulin stimulation. Surprisingly, intramyocellular
      lipids were well within the range of the control group. In conclusion, genetic
      CPT II deficiency is characterized by insulin resistance, which is not explained
      by increased intramyomellular lipids. However, it may be partially explained by
      glucose oxidation already maximally increased in the basal state, which cannot be
      increased any further by insulin. Reduced basal lipolysis may represent a
      compensatory mechanism for the reduced oxidative FFA disposal characteristic for
      this disease.

PMID- 11994356
TI  - Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E(90)K)
      GnRH receptor function by a deletion at a distant site.
AB  - GnRH regulates the synthesis and release of pituitary gonadotropins. Mutations in
      the human GnRH receptor (hGnRHR) gene have been reported in families with
      hypogonadotropic hypogonadism. Our group recently described a novel homozygous
      E(90)K mutation of the hGnRHR in two siblings with the complete form of
      hypogonadotropic hypogonadism. In the present study, mutational analysis of the
      E(90)K substitution was performed to assess the functional role of this
      particular residue, which is located in the second transmembrane helix of the
      hGnRHR. Although E(90) is highly conserved in all other known mammalian GnRH
      receptors, this residue has not been previously implicated in GnRH binding and/or
      GnRHR activation. Transient expression of the mutant E(90)K receptor in COS-7
      cells resulted in a virtual abolition of GnRH agonist binding and agonist
      stimulated phosphoinositide turnover, initially suggesting that E(90) may be
      essential for GnRH binding. Furthermore, incubation with 1 microM of different
      GnRH agonists (D-Trp(6)-GnRH, GnRH, leuprolide, Catfish-1 GnRH, Catfish-2 GnRH, D
      Lys(6)-Pro(9)-EA-GnRH, DesGly(10)-GnRH, D-Trp(6)-Pro(9)-EA-GnRH, Buserelin, and D
      Lys(6)-GnRH) or antagonists (Antide and "Nal-Arg") did not result in elevated
      inositol phosphate production from cells expressing the E(90)K mutant. To examine
      the role of a site known to suppress hGnRHR function, mutants with deletion of
      K(191) (DeltaK(191)) from the hGnRHR and/or addition of catfish GnRHR
      intracellular carboxyl-terminal tail (cfCtail) to hGnRHR were prepared. Exposure
      to the GnRH analog Buserelin resulted in a significant increase in total inositol
      phosphate production in cells expressing the hGnRHR-cfCtail, hGnRHR(DeltaK(191))
      and hGnRHR(DeltaK(191))-cfCtail. Activation of intracellular signaling in
      response to Buserelin was restored by deletion of K(191) from the E(90)K mutant
      receptor but minimally by addition of the catfish GnRHR carboxyl-terminal tail.
      There were no significant differences in total inositol phosphate production
      between the chimeric receptors bearing the DeltaK(191) or the E(90)K/DeltaK(191)
      modifications. All but the (E(90)K) and (E(90)K)-cfCtail altered receptors were
      membrane expressed as disclosed by Western blot analysis of epitope-tagged
      receptors. This study provides evidence that the E(90)K mutation impairs hGnRHR
      effector coupling. The observation that sequence modifications that enhance
      surface expression of the receptor restore function, presents the possibility
      that loss of surface expression may underlie the severe phenotype exhibited by
      hypogonadotropic hypogonadism patients bearing this mutational defect.

PMID- 11994357
TI  - Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post
      transcriptional changes in PKC epsilon.
AB  - PKC isozymes are the major binding proteins for tumor-promoting phorbol esters,
      and PKC activity is abnormal in a number of different human cancers. Less is
      known about putative structural and functional changes of specific PKC isozymes
      in human neoplasms. A single-point mutation of PKCalpha at position 881 of the
      coding sequence has been observed in human pituitary adenomas and up to 50% of
      thyroid follicular neoplasms, and a rearrangement of PKCepsilon was reported in a
      thyroid follicular carcinoma cell line, suggesting that these signaling proteins
      may play a role in thyroid tumorigenesis. To explore this possibility, we
      examined thyroid neoplasms for mutations and changes in expression levels of
      PKCepsilon or alpha. None of the 57 follicular adenomas, 26 papillary carcinomas
      (PCs), 7 follicular carcinomas, or the anaplastic carcinoma harbored the PKCalpha
      881A>G mutation. Moreover, none of 15 PCs, 10 follicular adenomas, or 6
      follicular carcinomas showed evidence of mutations of PKCepsilon. However, 8 of
      11 PCs had major isozyme-specific reductions of the PKCepsilon protein, which
      occurred through either translational or posttranslational mechanisms. These data
      indicate that post-transcriptional changes in PKCepsilon are highly prevalent in
      thyroid tumors and may play a significant role in their development.

PMID- 11994358
TI  - Circadian rhythm of serum cortisol after repeated inhalation of the new topical
      steroid ciclesonide.
AB  - The new inhalative glucocorticoid ciclesonide which is activated in lung to a
      more potent metabolite was hypothesized to have low risk for systemic and local
      side-effects in man. Therefore, a placebo-controlled, randomized, double-blind,
      four-period, change-over equivalence study in 12 healthy male volunteers (age 21
      28 yr, body weight 62-90 kg) was conducted to assess the influence of three
      dosage regimens (800 microg in the morning, 800 microg in the evening, 400 microg
      twice daily for 7 d, metered inhalers) on the circadian time serum cortisol
      rhythm. RESULTS: Serum cortisol showed the typical circadian rhythm. The
      geometric mean of the 24-h mesor (AUC((0-24 h))/24 h) was 7.22 microg/dl for
      placebo, 6.75 microg/dl for the 800 microg ciclesonide morning dose, 7.08
      microg/dl for the 800 microg evening dose, and 6.75 microg/dl for 400 microg
      ciclesonide inhaled twice daily. Because there was also no influence on cortisol
      amplitude and acrophase (time of maximum), the profiles after ciclesonide were
      equivalent to the placebo control. The small differences were considered not to
      be of clinical significance. In conclusion, inhaled ciclesonide in daily doses of
      800 microg for 7 d is without clinically relevant effects on the hypothalamic
      pituitary-adrenal axis independent of the time of administration.

PMID- 11994359
TI  - Sex and race differences in fat distribution among Asian, African-American, and
      Caucasian prepubertal children.
AB  - Sexual dimorphism in fat distribution is thought to emerge during puberty.
      Truncal or android body fat distribution is characteristic of adult males but is
      also recognized as a human cardiovascular risk factor. Race differences in
      truncal fat are clearly evident in adults and have been described in prepubertal
      children but not between Asians and other race groups. The aim of this study in
      African-American, Asian, and Caucasian prepubertal children was to evaluate sex
      differences and race differences in body fat distribution. Analysis of covariance
      was used to explore fat distribution in 358 prepubertal children (176 girls and
      182 boys; 143 Asians, 95 African-Americans, and 120 Caucasians), measured by
      skinfold thickness and dual-energy x-ray absorptiometry (DXA) in a cross
      sectional study. Extremity and gynoid fat masses were evaluated after adjustment
      for trunk or android fat, respectively, and for covariates including age, weight,
      height, and interactions. In Asian children, sex differences were present in
      models for gynoid fat by DXA only (P < 0.001), with girls having greater gynoid
      fat than boys. In African-American and Caucasian children, sex differences were
      present in models for extremity and gynoid fat masses, measured by both methods.
      Among girls, Asians had generally lower adjusted extremity and gynoid fat than
      Caucasians and African-Americans. Among boys, Asians had lower adjusted extremity
      fat by DXA than Caucasians (P < 0.01) but greater gynoid fat by skinfolds than
      African-Americans (P < 0.01). This study of prepubertal children demonstrates
      that: 1) sex differences in body fat distribution are present in prepubertal
      children but that the specific characteristics for Asians differ from African
      Americans and Caucasians, and 2) differences in body fat distribution in Asian
      children, compared with African-Americans and Caucasians, are present but vary by
      sex. This comparison of African-American, Asian, and Caucasian prepubertal
      children suggests phenotypic differences. Additional studies are needed to
      explore the metabolic and health risk implications of these findings.

PMID- 11994360
TI  - IGF-I, IGF binding protein (IGFBP)-3, phosphoisoforms of IGFBP-1, and postnatal
      growth in very low birth weight infants.
AB  - Impaired postnatal growth in very low birth weight (VLBW, <1500 g) infants is per
      se a major clinical challenge and may also serve as a model in studying the
      mechanisms of growth retardation in general. This study was undertaken to
      characterize the role of IGFs and their binding proteins (IGFBPs), key regulators
      of fetal and infant growth, during the postnatal period in VLBW infants. Forty
      eight VLBW infants (gestational age 27.6 +/- 2.2 wk, birth weight 923 +/- 257 g)
      were studied. Blood samples were drawn at 1, 2, 4, and 8 wk of age for
      measurements of IGF-I, IGFBP-1 (lesser phosphorylated, lpIGFBP-1, and highly
      phosphorylated, hpIGFBP-1), IGFBP-3, and insulin, simultaneous growth velocities
      being assessed by a rigorous protocol of repeated, frequent lower leg length and
      body weight measurements. All regression analyses were adjusted for postnatal age
      and repeated measurements. Lower leg growth velocity showed a positive
      correlation with IGF-I (P = 0.01) and IGFBP-3 (P = 0.03), and weight growth
      velocity with IGFBP-3 (P = 0.057) and with lpIGFBP-1/hpIGFBP-1 ratio (P = 0.01).
      Moreover, concurrent glucocorticoid dose showed a negative correlation with both
      IGFBP-1 isoforms, observable, however, only in samples with high (>10 U/liter)
      insulin (lpIGFBP-1, P = 0.02; hpIGFBP-1, P = 0.007). In backward multiple
      regression analysis, the factor remaining significantly associated with lower leg
      growth velocity (R(2) = 0.63) was IGF-I, and factors associated with weight
      growth velocity (R(2) = 0.81) were IGFBP-3 and the lpIGFBP-1/hpIGFBP-1 ratio. In
      conclusion, circulating IGF-I and IGFBP-3, and the lpIGFBP-1/hpIGFBP-1 ratio,
      reflect short-term growth velocity in VLBW infants. lpIGFBP-1 isoforms, abundant
      in the circulation of these infants, may thus also have properties that are at
      least less inhibitory, if not promoting, on the growth-stimulating action of IGF
      I. Finally, the regulation of IGFBP-1 by glucocorticoids may be divergent in
      situations with a high or low insulin concentration.

PMID- 11994361
TI  - Glycated low density lipoproteins modify platelet properties: a compositional and
      functional study.
AB  - The interaction between low density lipoproteins (LDL) and platelets might play a
      central role in the development of atherosclerosis in diabetes. The aim of the
      present study was to investigate whether the glycation of LDL is associated with
      modifications of their physico-chemical and functional properties and to study
      the action of glycated LDL (glycLDL) on platelets. LDL and platelets were
      isolated from 15 healthy subjects. The content of thiobarbituric acid-reactive
      substances and the generalized polarization of the fluorescent probe Laurdan were
      determined in LDL glycated in vitro. Platelets were incubated with native LDL,
      GlycLDL, and minimally oxidized LDL, and the following parameters were evaluated:
      platelet aggregation, nitric oxide production, intracellular Ca(2+)
      concentrations, Na(+)/K(+)-adenosine triphosphatase (Na(+)/K(+)-ATPase), and
      Ca(2+)-ATPase activities. GlycLDL showed increased thiobarbituric acid-reactive
      substance levels, a red shift of the Laurdan emission maximum, and a decrease in
      generalized polarization, indicating a higher polarity and a reduced molecular
      order compared with native LDL. GlycLDL caused a significant increase in platelet
      nitric oxide production, intracellular Ca(2+) concentration, and aggregating
      response to ADP; an inhibition of the platelet membrane Na(+)/K(+)-ATPase
      activity; and a stimulation of Ca(2+)-ATPase activity. Minimally oxidized LDL did
      not cause statistically significant changes in the parameters studied. The
      present work demonstrates that glycation induces compositional and structural
      changes in LDL and suggests that an altered interaction between glycLDL and
      platelets might play a role in the vascular complications of diabetes.

PMID- 11994362
TI  - Body composition and circulating levels of insulin, insulin-like growth factor
      binding protein-1 and growth hormone (GH)-binding protein affect the
      pharmacokinetics of GH in adults independently of age.
AB  - The aim of our study was to scrutinize the association among age, body
      composition, and GH status in healthy adults. Using two-step, primed constant
      infusions of GH during suppression of endogenous GH secretion with octreotide in
      a group of 26 healthy nonobese men [mean age, 37.3 yr (range, 22-55 yr); body
      mass index, 24.6 +/- 0.4 kg/m(-2)] we investigated the contributions of age, body
      composition, insulin, and binding proteins to the variability in the
      pharmacokinetics and acute actions of GH. All subjects were investigated twice,
      with the infusion rates of GH calculated according to either total body weight or
      intraabdominal fat mass. Body composition was determined using computed
      tomography and bioimpedance measurements. There was no correlation between age
      and body weight, yet strong positive correlations were observed between age and
      intraabdominal fat area (r = 0.78; P < 0.0001) and waist to hip ratio (r = 0.71;
      P < 0.0001) and to a lesser degree to sc fat area (r = 0.42; P < 0.03). The
      between-subject variability in steady state GH levels was significantly larger
      when GH was administered per cm(2) intraabdominal fat area than per kg BW (P <
      0.001). During primed constant infusions of GH at rates of 1.5 and 3.0 microg/kg
      x h, the corresponding MCRs of GH were 148.8 +/- 5.4 and 89.8 +/- 2.4 ml/min x m(
      2), respectively, and the MCRs were inversely related to the achieved steady
      state GH levels (P < 0.0001). The MCR was unrelated to age, but was negatively
      correlated to baseline concentrations of IGF-binding protein-1 (IGFBP-1; r = 
      0.53, P < 0.01) and positively correlated to basal levels of insulin (r = 0.46; P
      < 0.05), GH-binding protein (GHBP; r = 0.52; P < 0.01), IGFBP-3 (r = 0.47; P <
      0.05), and total body fat (r = 0.44; P < 0.05). GH infusion caused significant
      changes in the concentrations of IGF-I, free fatty acids, GHBP, IGFBP-1, and
      insulin, but none of these effects was correlated to age. Based on our results we
      conclude that 1) the clearance of GH is concentration dependent; 2) the
      pharmacokinetics and acute effects of GH are not affected by age per se; and 3)
      basal levels of insulin, IGFBP-1, and GHBP as well as age-related changes in body
      composition are important predictors of GH pharmacokinetics.

PMID- 11994363
TI  - Hypothalamic regulation of cyclic ovulation: evidence that the increase in
      gonadotropin-releasing hormone pulse frequency during the follicular phase
      reflects the gradual loss of the restraining effects of progesterone.
AB  - The luteal-follicular transition is characterized by decreasing plasma levels of
      E(2), progesterone (P), and inhibin A, with concomitant increases in FSH and LH
      levels. LH (and by inference GnRH) pulse frequency increases from 1 pulse every 3
      4 h during the luteal phase to approximately 1 pulse/h at the midcycle LH surge.
      To examine the regulation of GnRH pulse frequency, we gave 10 normally cycling
      women transdermal E(2) and oral P to produce midluteal levels [364 +/- 65.0
      pmol/liter (99 +/- 18 pg/ml) and 29.7 +/- 6.8 nmol/liter (9.3 +/- 2.1 ng/ml),
      respectively] for 10 d after the LH surge (d 0). P was then discontinued, and
      E(2) was given alone for 3 additional wk. Pulsatile LH secretion and follicular
      size were assessed on d 10, 17, 24, and 31. Results are presented as the mean +/-
      SEM. LH pulse frequency was 3.1 +/- 0.5 pulses/12 h after 10 d of E(2) and P, and
      remained low on d 17 when P had fallen below 1.6 nmol/liter (<0.5 ng/ml). In the
      continued presence of midluteal levels of E(2) [ approximately 360 pmol/liter
      (100 pg/ml)], LH pulse frequency increased on d 24 and 31 to 5.5 +/- 0.9 and 5.8
      +/- 0.5 pulses/12 h, respectively, whereas pulse amplitude remained unchanged.
      FSH increased 2-fold, but follicular size did not change. These results are
      consistent with E(2) potentiating the effects of low concentrations of P on the
      GnRH pulse generator for at least 7 d, after which pulse frequency increases
      despite maintenance of E(2) levels. This supports the hypothesis that the
      increasing GnRH pulse frequency throughout the follicular phase reflects the
      gradual loss of the inhibitory actions of low concentrations of P.

PMID- 11994364
TI  - Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid
      cells.
AB  - The calcium-sensing receptor (CaR) activation has recently been shown to modulate
      the ERK1 and ERK2 cascade in different cell lines. The present study investigated
      this pathway in human normal and tumoral parathyroid cells. In cells from normal
      parathyroids and almost all hyperplasia increasing extracellular calcium
      concentrations (Ca(o)(2+)) induced a significant activation of ERK1 and -2, the
      percent stimulation over basal activity (at 0.5 mM Ca(o)(2+)) being 545 +/- 140
      and 800 +/- 205 in normal cells and 290 +/- 71 and 350 +/- 73 in hyperplasia at 1
      and 2 mM Ca(o)(2+), respectively. This effect was mediated by CaR because it was
      mimicked by the receptor agonist gadolinium and neomycin. Basal and Ca(o)(2+)
      stimulated ERK1 and -2 activity was nearly abolished by the PKC inhibitor
      calphostin C, and PKA changes did not affect ERK1 and -2 activity. PI3K blockade
      by wortmannin, known to prevent G protein betagamma subunit effect on ERK1 and 
      2, induced a 30% reduction of the Ca(o)(2+)-stimulated ERK1 and -2 activity.
      Adenomatous cells showed high PKC-dependent ERK1 and -2 activity in resting
      conditions that was unresponsive to high Ca(o)(2+). A role of MAPK on PTH
      secretion was suggested by the finding that PD98059, a specific MEK inhibitor,
      abolished the inhibitory effect of 1.5 mM Ca(o)(2+) on PTH release from normal
      parathyroid cells. In conclusion, these data first demonstrate that CaR
      activation, through the PKC pathway and, to a lesser extent, PI3K, increases ERK1
      and -2 activity in normal parathyroid cells and this cascade seems to be involved
      in the modulation of PTH secretion by Ca(o)(2+). Interestingly, this signaling
      pathway is disrupted in parathyroid tumors.

PMID- 11994365
TI  - Measurements of interstitial muscle glycerol in normal and insulin-resistant
      subjects.
AB  - The aim of this project was to study the regulation of interstitial glycerol
      levels in muscle in normal subjects, and to estimate interstitial muscle glycerol
      in obese subjects and patients with type 2 diabetes. In healthy lean subjects,
      microdialysis of forearm sc and muscle tissue were combined with arterial and
      deep venous catheterization, as well as blood flow registrations during oral
      glucose ingestion. In two other separate studies, obese (n = 9) vs. lean (n = 10)
      subjects and type 2 diabetes patients (n = 8) vs. weight-matched control subjects
      (n = 8) were investigated by means of muscle microdialysis during a euglycemic
      hyperinsulinemic clamp. Oral glucose ingestion suppressed the interstitial sc
      glycerol concentration by approximately 40% (P < 0.05), whereas no significant
      reduction of muscle interstitial glycerol was found. In contrast to the
      significant muscle interstitial-arterial (I-A) glycerol difference, the venous
      arterial difference was small and varying throughout the oral glucose tolerance
      test. At steady-state hyperinsulinemia, obese subjects' interstitial muscle
      glycerol and I-A glycerol difference were both significantly higher than lean
      controls, whereas type 2 diabetes patient had interstitial muscle glycerol
      concentrations and I-A glycerol differences similar to those found in weight
      matched controls. A significant and marked I-A glycerol difference exists in the
      absence of a significant venous-arterial difference, indicating that muscle
      glycerol cannot be taken as a marker of intramyocellular lipolysis because local
      turnover of muscle glycerol might be significant. The present data also suggest
      that, in contrast to sc tissue, muscle tissue lacks a clear antilipolytic effect
      of insulin. Moreover, the muscle interstitial glycerol concentration is elevated
      in obese patients but does not precipitate insulin resistance and type 2
      diabetes.

PMID- 11994366
TI  - Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of
      creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but
      does not identify gene carriers.
AB  - Autosomal dominant osteopetrosis type II (ADO2) is typically diagnosed from
      radiographs, which demonstrate the pathognomonic findings of osteosclerosis and
      endobone formation. Individuals with ADO2 also have elevated serum levels of
      tartrate-resistant acid phosphatase (TRAP) and the BB isoenzyme of creatine
      kinase (CK-BB). In the current study, we tested the utility of these enzymes in
      making or refuting a diagnosis of ADO2. Furthermore, because ADO2 has incomplete
      penetrance, we examined whether TRAP and CK-BB were helpful in identifying gene
      carriers. We studied eight families, measured serum levels of TRAP and CK-BB in
      52 affected individuals and 12 obligate gene carriers, and compared their values
      with age-matched controls. Our results demonstrate that affected patients have
      significantly elevated levels of both TRAP and CK-BB. In contrast, gene carriers
      have values that are not different from controls. Furthermore, in our study
      population, TRAP and CK-BB have a high diagnostic sensitivity and specificity,
      particularly in children. From this large study of ADO2 patients and carriers, we
      conclude that: 1) TRAP and CK-BB are significantly elevated in patients with
      ADO2, 2) obligate carriers cannot be adequately identified by measurement of
      these analytes, and 3) TRAP and CK-BB are highly sensitive and specific
      diagnostic tests that can efficiently and effectively screen high-risk
      individuals who have not had previous radiographic assessment.

PMID- 11994367
TI  - Contribution of insulin secretion and clearance to glucose-induced insulin
      concentration in african-american and caucasian children.
AB  - Relative to Caucasians (C), African-American (AA) children and adults have lower
      indices of insulin sensitivity (S(i)) and a higher acute insulin response to
      glucose (AIR(g)). Among AA children, AIR(g) is greater than that which would be
      predicted based on lower S(i). The objectives of the present study were 1) to
      determine whether insulin secretory parameters differ in AA vs. C children and
      adolescents using C-peptide modeling, 2) to determine whether hepatic insulin
      extraction differs with ethnicity/race using the C-peptide to insulin molar
      ratio, and 3) to determine whether the relatively greater AIR(g) among African
      Americans is due to greater insulin secretion or lesser clearance. Subjects (n =
      76) were AA and C children (mean age, approximately 11 yr). A 3-h tolbutamide
      modified iv glucose tolerance test and minimal modeling were used to determine
      S(i) and AIR(g). First phase C-peptide/insulin secretion and basal, first, and
      second phase beta-cell sensitivity to glucose were determined using C-peptide
      modeling with standard kinetic parameters developed in adults. The incremental C
      peptide to insulin molar ratio over the 3-h test period, an index of hepatic
      insulin extraction, was calculated with the trapezoidal method. S(i) was lower
      and AIR(g) was higher in AA vs. C children. First phase C-peptide/insulin
      secretion and first phase beta-cell sensitivity to glucose were approximately 2
      fold greater in AA vs. C children (P < 0.001); there were no between-group
      differences in basal or second phase beta-cell sensitivity to glucose. Hepatic
      insulin extraction was lower in AA vs. C (3.77 +/- 1.78% vs. 5.99 +/- 2.18%; P <
      0.001). Multiple linear regression modeling indicated that first phase C
      peptide/insulin secretion and hepatic insulin extraction contributed
      independently to AIR(g); however, it was only first phase C-peptide/insulin
      secretion that explained the significant independent contribution of
      ethnicity/race to AIR(g) after adjusting for S(i). The results of this study
      suggest that greater AIR(g) among AA is due to both greater insulin secretion and
      lesser hepatic insulin extraction, and that AIR(g) above that predicted based on
      lower S(i) is due to greater insulin secretion. The insulin secretion data await
      verification that the kinetic parameters used apply to children and AA.

PMID- 11994368
TI  - Sex- and age-related changes in epitestosterone in relation to pregnenolone
      sulfate and testosterone in normal subjects.
AB  - Epitestosterone has been demonstrated to act at various levels as a weak
      antiandrogen. So far, its serum levels have been followed up only in males.
      Epitestosterone and its major circulating precursor pregnenolone sulfate and T
      were measured in serum from 211 healthy women and 386 men to find out whether
      serum concentrations of epitestosterone are sufficient to exert its
      antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20
      yr of age, followed by a continuous decline up to menopause and by a further
      increase in the postmenopause. In men, maximum epitestosterone levels were
      detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone
      sulfate levels in women reached their maximum at about age 32 yr and then
      declined continuously, and in males the maximum was reached about 5 yr earlier
      and then remained nearly constant. Epitestosterone correlated with pregnenolone
      sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T
      ratio around puberty occurred. In conclusion, concentrations of epitestosterone
      and pregnenolone sulfate are age dependent and, at least in prepubertal boys and
      girls, epitestosterone reaches or even exceeds the concentrations of T, thus
      supporting its role as an endogenous antiandrogen. The dissimilarities in the
      course of epitestosterone levels through the lifespan of men and women and its
      relation to pregnenolone sulfate concentrations raise the question of the
      contribution of the adrenals and gonads to the production of both steroids and
      even to the uniformity of the mechanism of epitestosterone formation.

PMID- 11994369
TI  - Inadequate luteal function is the initial clinical cyclic defect in a 12-day
      stress model that includes a psychogenic component in the Rhesus monkey.
AB  - As part of our goal to develop nonhuman primate models to prospectively study how
      different types of stress may affect the menstrual cycle, we have investigated
      whether a short-term stress challenge that includes a significant psychogenic
      component can induce cyclic dysfunction. The study was performed in rhesus
      monkeys. The stress challenge had several components that included the
      psychological response to both a tethering system and to a simultaneous move to
      an unfamiliar environment and the response to the short surgical procedures
      required to install and disconnect the tethering system. The stress challenge
      lasted for 12 d and was initiated in the follicular (n = 5) or luteal (n = 6)
      phase of the menstrual cycle. At the end of the stress period, the tethering
      system was removed, and the animal was returned to its regular housing. To
      monitor cyclicity, FSH, LH, E2, and progesterone were measured daily throughout
      the two preceding control cycles, the experimental cycle, and the two poststress
      cycles, whereas the adrenal endocrine axis response was monitored by measuring
      cortisol. Animals remained ovulatory after the short-term stress; however,
      integrated progesterone secretion in the luteal phase (from the day of LH surge
      +1 to the day of menstruation -1) of the stress cycle was significantly decreased
      by 51.6% when the stress was initiated in the follicular phase and by 30.9% when
      it started in the luteal phase. Lower integrated LH levels (luteal d 5-13)
      accompanied the decreased progesterone. Cyclic parameters were still abnormal in
      the first poststress cycle, such as a prolonged follicular phase after a stress
      in the preceding follicular phase or inadequate luteal function after a stress in
      the preceding luteal phase. Within 4 h of the stress, there was a rapid 3-fold
      increase in cortisol levels over controls. Levels decreased progressively
      thereafter but remained significantly higher than controls during the entire
      short-term stress period. They were still significantly higher in the first 2 wk
      after stress. Overall, the data suggest that secretory inadequacy of the corpus
      luteum represents a first clinical stage in the damage that stress can inflict on
      the normal menstrual cycle. Of interest is the observation that this limited 12-d
      stress, which includes a significant psychogenic component, continues to produce
      detrimental effects on the menstrual cycle past the period during which it is
      exerted. Significant decreases in integrated luteal LH values in the poststress
      cycle suggest that these effects may be related to continuing disturbances in the
      neuroendocrine component of the reproductive axis.

PMID- 11994370
TI  - Oral hydrocortisone administration in children with classic 21-hydroxylase
      deficiency leads to more synchronous joint GH and cortisol secretion.
AB  - In humans, GH and cortisol are secreted in a pulsatile fashion and a mutual
      bidirectional interaction between the GH/IGF-I axis and hypothalamic-pituitary
      adrenal axis has been established. Classic congenital adrenal hyperplasia (CAH)
      is characterized by a defect in the synthesis of glucocorticoids and often
      mineralocorticoids, and adrenal hyperandrogenism. Substitution therapy is given
      to prevent adrenal crises and to suppress the abnormal secretion of androgens and
      steroid precursors from the adrenal cortex. However, treatment with twice or
      three times daily oral hydrocortisone does not mimic physiological adrenal
      rhythms and may influence the activity of the GH/IGF-I axis. We investigated the
      pattern of GH and cortisol secretion and the synchrony of joint GH-cortisol
      secretory dynamics in 15 children with classic 21-hydroxylase deficiency (5 males
      and 10 females; median age 9.5 yr, range 6.1-11.0 yr) and 28 short normal
      children (23 males and 5 females; median age 7.7 yr, range 4.9-9.3 yr). All
      subjects were prepubertal. Serum GH and cortisol concentrations were determined
      at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was
      assessed using approximate entropy (ApEn), a scale- and model-independent
      statistic. The synchrony of joint GH-cortisol secretion was quantified using the
      cross-ApEn statistic. Cross-correlation analysis of GH and cortisol secretory
      patterns was computed at various time lags covering the 24-h period. Children
      with CAH had significantly lower mean 24-h serum cortisol concentrations (6.4 +/-
      2.2 vs. 10.4 +/- 2.6 microg/dl, P < 0.001), ApEn (GH) (0.64 +/- 0.13 vs. 0.74 +/-
      0.17, P = 0.04), ApEn (cortisol) (0.54 +/- 0.13 vs. 1.08 +/- 0.18, P < 0.001) and
      cross-ApEn values of paired GH-cortisol secretion (0.78 +/- 0.19 vs. 1.05 +/-
      0.12, P < 0.001) than normal children. There was no difference in mean 24-h GH
      concentrations between the two groups (4.5 +/- 2.9 vs. 4.5 +/- 1.9 mU/liter). In
      children with CAH, a significant positive correlation between GH and cortisol was
      noted at lag time 0 min (r = 0.299, P < 0.01), peaking at 20 min (r = 0.406, P <
      0.0001), whereas in normal children, a significant negative correlation between
      the two hormones was noted at lag time 0 min (r = -0.312, P < 0.01). The above
      findings suggest that children with classic CAH have a more regular pattern of GH
      secretion and a more synchronous joint GH-cortisol secretory dynamics than their
      normal counterparts. These differences reflect bidirectional interactions between
      the GH/IGF-I axis and hypothalamic-pituitary-adrenal axis in humans, and are
      likely to evolve as a result of the exogenous administration of hydrocortisone at
      fixed doses and at specific time intervals, which leads to a more regular pattern
      in circulating cortisol concentrations, independent of variations in CRH and ACTH
      concentrations.

PMID- 11994371
TI  - Follicle-stimulating hormone activates mitogen-activated protein kinase in
      preneoplastic and neoplastic ovarian surface epithelial cells.
AB  - To investigate the role of FSH in ovarian cancer development, the present study
      examined the expression of FSH receptor (FSH-R) and the effect of FSH on
      proliferation of normal, preneoplastic, and neoplastic ovarian surface epithelium
      (OSE) cells. Recently, immortalized OSE (IOSE) cell lines, including IOSE-29
      (preneoplastic) and IOSE-29EC (neoplastic), were used. Our results indicated that
      FSH-R mRNA was expressed and that FSH exerted a growth stimulatory effect in
      normal, preneoplastic, and neoplastic OSE cells. To investigate the mechanism of
      the growth stimulatory effect, the activation of MAPKs by FSH was examined in
      preneoplastic and neoplastic OSE cells. Treatment with FSH resulted in MAPK
      activation of IOSE-29 and IOSE-29EC cells, whereas the stimulatory effect of FSH
      on cellular proliferation and MAPK activation was completely abolished in the
      presence of PD98059, a MAPK kinase inhibitor, suggesting that the growth
      stimulatory effect of FSH is mediated through MAPK activation in these OSE cells.
      In a time-dependent study, FSH significantly increased MAPK activity at 5-10 min
      in IOSE-29 cells. The activated MAPK declined to the control level after 20 min
      in these cells. Similarly, treatment with FSH significantly induced MAPK
      activation after 5 min and sustained it for 60 min in IOSE-29EC cells. In
      addition, treatment with FSH resulted in substantial phosphorylation of Elk-1,
      confirming that FSH action is mediated via activation of MAPK. In conclusion, we
      have demonstrated that FSH-R was expressed, and FSH induced growth stimulation in
      normal, preneoplastic, and neoplastic OSE cells. Furthermore, treatment with FSH
      stimulated activation of the MAPK cascade and phosphorylated Elk-1 in neoplastic
      OSE cells. These results suggest that the MAPK cascade may be involved in
      cellular functions such as growth stimulation in response to FSH in preneoplastic
      and neoplastic OSE cells.

PMID- 11994372
TI  - The Karlsburg type 1 diabetes risk study of a normal schoolchild population:
      association of beta-cell autoantibodies and human leukocyte antigen-DQB1 alleles
      in antibody-positive individuals.
AB  - The intent of this study was to analyze the prevalence of diabetes-associated
      autoantibodies (AAbs) at or above the 99(th) percentile as well as their
      association with human leukocyte antigen (HLA)-DQB1 alleles in a normal
      population of 6,337 schoolchildren. AAbs against glutamic acid decarboxylase
      (GADA), tyrosine phosphatase IA-2 (IA-2A), and/or insulin (IAA) were detected by
      (125)I-antigen binding and islet cell antibodies (ICA) immunohistochemically in
      181 (2.86%) schoolchildren. HLA-DQB1 alleles were analyzed in 178/181 children
      and subsequently compared with 119 controls. 2.37% (150/6,337) possessed only one
      AAb, whereas 0.49% (31/6,337) had multiple AAbs but at increased levels (P <
      0.001). Subjects with GADA, IA-2A, or IAA revealed an increased frequency of the
      diabetes-associated HLA-DQB1 alleles *0302 and/or *02 (P = 0.001-0.006) as well
      as a decreased frequency in the protective allele *0602 (P < 0.001-0.022).
      DQB1*0602 was completely absent within children with multiple AAbs or with GADA,
      IA2-A, or IAA at or above the 99.9(th) percentile. In comparison to children with
      single AAbs, the frequency of associated/protective alleles of children with
      multiple AAbs was enhanced/diminished (P = 0.004-0.009). The study shows that
      also in the general population the multiple AAbs or high level single AAbs
      predict rather certainly a HLA-DQB1-mediated diabetes susceptibility as shown for
      first degree relatives of type 1 diabetic patients.

PMID- 11994373
TI  - High serum allopregnanolone levels in girls with precocious puberty.
AB  - Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the
      modulation of behavioral functions, stress, and the neuroendocrine axis. The aim
      of this study was to evaluate serum allopregnanolone concentrations in girls with
      central precocious puberty (n = 12), girls with normal pubertal development at
      the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16).
      Gonadotropin and steroid hormones (allopregnanolone, cortisol,
      dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and
      ACTH stimulation tests were performed in all girls with central precocious
      puberty and in some pubertal controls. Basal allopregnanolone levels in girls
      with central precocious puberty were significantly higher than in normal controls
      (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH
      stimulation tests (P < 0.05) both in girls with central precocious puberty and in
      those with normal pubertal development. There was no difference found between the
      peak values. In conclusion, our study shows that allopregnanolone is
      hypersecreted in central precocious puberty, confirming a pubertal stage-related
      increase in its levels during normal pubertal development. The increase in serum
      allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both
      adrenal cortex and gonads are sources of this neuroactive steroid.

PMID- 11994374
TI  - Follicle-stimulating hormone receptors in oocytes?
AB  - The regulatory mechanisms of oocyte maturation remain poorly understood. Although
      gonadotropins play a major role in these processes, they have generally been
      considered to act on somatic supportive cells, but not directly on germ cells. We
      have raised high affinity monoclonal antibodies against LH and FSH receptors.
      When using the latter to study receptor distribution in human and pig ovaries we
      have observed the presence of FSH (but not LH) receptors in the oocytes. FSH
      receptors appeared in the oocytes of primary follicles during follicular
      development and persisted up to the preovulatory stage. In denuded human
      preovulatory oocytes, FSH receptor mRNA was detected at a concentration per cell
      exceeding by about 20-fold that present in granulosa cells. Saturable binding of
      [(125)I]FSH to the membrane of oocytes was demonstrated by autoradiography. When
      incubated with FSH, denuded oocytes responded by a mobilization of Ca(2+). These
      observations concur to demonstrate the presence of functional FSH receptors in
      oocytes and raise the possibility of direct control of oocyte development by FSH.

PMID- 11994376
TI  - Serum and tissue expression of activin a in postmenopausal women with breast
      cancer.
AB  - Activins are growth factors involved in the control of cell proliferation and
      differentiation. Human breast tissues express immunoreactive activin subunits,
      and activin A is able to inhibit the replication of mammary cells in vitro. The
      aim of the present study was to evaluate 1) whether breast cancer expresses
      activin betaA subunit mRNA, 2) whether serum activin A levels are altered in
      postmenopausal women with breast cancer, and 3) how circulating activin A levels
      change after tumor removal. Four groups of women (n = 158) were enrolled for the
      present prospective study: two groups were composed of postmenopausal women with
      breast cancer (n = 74) or benign lesions (n = 15); the third was a control group
      composed of healthy postmenopausal women (n = 62); and the fourth group included
      healthy fertile women (n = 7) undergoing plastic surgery with removal of non
      neoplastic mammary tissue. RT-PCR showed that betaA subunit mRNA was expressed in
      breast carcinoma, fibroadenoma, and normal mammary tissue, and the level of
      expression was higher in carcinoma than in normal tissue (P < 0.05). Dimeric
      activin A was detectable in homogenates of breast cancer tissue at concentrations
      twice as high as in non-neoplastic tissue (P < 0.01). In women with breast
      cancer, median serum activin A levels were significantly higher than in controls
      (P < 0.001). The high serum activin A levels in patients with breast cancer were
      not correlated with the presence of lymph node metastasis, tumor grade, or tumor
      diameter. After tumor excision, a significant decrease of activin A in the first
      and second postoperative days was observed (P < 0.01; Friedman's ANOVA).
      Conversely, activin A levels remained unchanged after plastic surgery in healthy
      women. The present results suggest that activin A is expressed and secreted in
      postmenopausal women with breast cancer. The pathophysiological and possible
      clinical implications of this finding remain to be investigated.

PMID- 11994377
TI  - Mechanism of action of a 3-hydroxy-3-methylglutaryl coenzyme a reductase
      inhibitor on apolipoprotein B-100 kinetics in visceral obesity.
AB  - We examined the effect of atorvastatin, an inhibitor of 3-hydroxy-3
      methylglutaryl coenzyme A reductase, on the kinetics of apolipoprotein B-100
      (apoB) metabolism in 25 viscerally obese men in a placebo-controlled study. Very
      low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low
      density lipoprotein (LDL) apoB kinetics were measured using an iv bolus injection
      of [(2)H(3)]leucine. ApoB isotopic enrichment was measured using gas
      chromatography-mass spectrometry. Kinetic parameters were derived by using a
      multicompartmental model (SAAM-II). Compared with the placebo group, atorvastatin
      treatment resulted in significant (P < 0.001) decreases in total cholesterol (
      34%), triglyceride (-19%), LDL cholesterol (-42%), total apoB (-39%), and
      lathosterol (-86%); VLDL-apoB, IDL-apoB, and LDL-apoB pool sizes also fell
      significantly (P < 0.002) by -27%, -22%, and -41%, respectively. This was
      associated with an increase in the fractional catabolic rates of VLDL-apoB (+58%,
      P = 0.019), IDL-apoB (+40%, P = 0.049), and LDL-apoB (+111%, P = 0.001). However,
      atorvastatin did not significantly alter the production and conversion rates of
      apoB in all lipoproteins. We conclude that in obese subjects, atorvastatin
      decreases the plasma concentration of all apoB-containing lipoproteins chiefly by
      increasing their catabolism and not by decreasing their production or secretion.
      This may be owing to up-regulation of hepatic receptors as a consequence of
      inhibition of cholesterogenesis.

PMID- 11994378
TI  - Evidence that GnRH decreases with gonadal steroid feedback but increases with age
      in postmenopausal women.
AB  - Studies of the effects of gonadal steroid negative feedback and age on the
      hypothalamic-pituitary axis in postmenopausal women (PMW) have identified
      significant but inconsistent changes in gonadotropin dynamics. In the current
      study, we investigated the effect of gonadal steroid replacement and age on
      overall GnRH secretion estimated by using submaximal GnRH receptor blockade.
      Twenty-four healthy PMW, 45-55 yr (n = 13) and 70-80 yr (n = 11), were studied.
      Subjects were studied at baseline (BL) on no hormone replacement therapy, after 1
      month of transdermal estrogen (50 microg/d; E) and again after a further month of
      E and 7 d of transvaginal progesterone (100 mg bid; E + P). At each admission,
      blood was sampled every 30 min for 4 (BL and E) or 8 h (E + P) before and 10 h
      after sc administration of a submaximal dose (5 microg/kg) of the NAL-GLU GnRH
      antagonist ([Ac-D2Nal(1), D4ClPhe(2), DPal(3), Arg(5), DGlu(AA)(6), DAla(10)]
      GnRH). Percent inhibition of LH was calculated by expressing the difference
      between the nadir following GnRH antagonist administration and the preantagonist
      baseline as a percent of the baseline. Physiologic E and P levels were achieved
      with the appropriate hormone replacement regimens. Mean LH levels decreased from
      baseline with E alone and decreased further with E + P (81.4 +/- 6.6, 68.2 +/-
      8.1 and 48.0 +/- 4.3 IU/liter, respectively; P < 0.005). Percent inhibition of LH
      following submaximal GnRH receptor blockade decreased with age (57.6 +/- 1.8% in
      young PMW vs. 51.4 +/-2.2% in old PMW; P < 0.05) implying an increase in GnRH
      secretion with age. There was an increase in percent inhibition of LH in response
      to submaximal GnRH receptor blockade with E and a further increase with E + P
      (54.8 +/-1.5%, 58.8 +/- 1.9% and 69.9 +/- 2.8%, respectively; P < 0.05),
      indicating a progressive decrease in endogenous GnRH secretion with gonadal
      steroid feedback. Mean LH and FSH levels were lower at baseline in old compared
      with young PMW. However, the effect of gonadal steroid feedback on endogenous
      GnRH secretion was similar in young and old PMW. IN CONCLUSION: 1) The overall
      quantity of GnRH secretion increases with age as demonstrated by the progressive
      decrease in LH inhibition following submaximal GnRH antagonist administration
      with increasing age; 2) E negative feedback is associated with a decrease in GnRH
      secretion (as indicated by an increased percent inhibition of LH following
      submaximal GnRH receptor blockade); 3) E2 and P are associated with a further
      decease in overall amount of GnRH secreted; and 4) Age does not dampen the
      inhibition of hypothalamic GnRH secretion by E and P in PMW.

PMID- 11994380
TI  - Negative feedback effects of gonadal steroids are preserved with aging in
      postmenopausal women.
AB  - There is now evidence for alterations in the neuroendocrine control of the
      reproductive axis with aging, but its sensitivity to gonadal steroid negative
      feedback remains controversial. To examine the independent effect of age and
      gonadal steroid negative feedback, younger (45-55 yr; n = 7) and older (70-80 yr;
      n = 6) postmenopausal women (PMW) were studied at baseline on no HRT, after 1
      month of transdermal estrogen (50 microg/d; E) and again after a further month of
      E and 7 d of transvaginal progesterone (P) (100 mg bid; E + P). At each
      admission, blood was sampled every 5 min for 8 h for measurement of gonadotropin
      free alpha-subunit (FAS), which was used as a marker of GnRH pulse frequency. LH
      and FSH were measured in pooled samples. Midfollicular and midluteal phase levels
      of E2 and P were achieved during the E and E + P treatments and were not
      different between younger and older PMW. There was a negative feedback effect of
      E and E + P on mean LH (P < 0.0001) and an additional effect of age (P < 0.003),
      with older women having lower values throughout. Mean FSH was also decreased with
      E and E + P (P < 0.0001) and was consistently lower in the older women (P <
      0.05). Mean FAS levels decreased with hormonal treatment (P < 0.0001) and age (P
      < 0.001), but the effect of hormonal treatment was attenuated in the older group
      (P < 0.005). FAS pulse frequency was unchanged with addition of E, but
      dramatically decreased with E + P (P < 0.002). Both hormonal replacement (P <
      0.05) and age (P < 0.005) decreased FAS pulse amplitude, an effect that was
      attributable entirely to E as there was no additional change with E + P. These
      studies indicate that: 1) both age and gonadal steroids independently decrease
      mean LH, FSH, and FAS in PMW; 2) responsiveness to steroid negative feedback on
      FAS is attenuated with aging in absolute but not relative terms, whereas the
      effect on mean levels of LH and FSH is clearly preserved; and 3) FAS pulse
      frequency is unchanged with E2 administration but decreases dramatically with
      addition of P in both old and young PMW.

PMID- 11994381
TI  - Premenstrual disappearance of aminopeptidase A in endometrial stromal cells
      around endometrial spiral arteries/arterioles during the decidual change.
AB  - Aminopeptidase A (APA, BP-1) is a membrane-bound zinc metallopeptidase that
      converts angiotensin II (AngII) into AngIII by selectively hydrolyzing the N
      terminal aspartyl residue. AngII has been proposed as a candidate for the initial
      vasoconstrictor of endometrial spiral arteries/arterioles in the preliminary step
      of menstruation. In the late secretory phase, endometrial stromal cells (ESC)
      around the blood vessels begin to differentiate into decidual cells, and AngII
      has been reported to accumulate around such vessels. However, whether there is a
      concurrent increase in renin or angiotensin-converting enzyme in this area has
      not been determined. We hypothesized that APA may be involved in the metabolism
      of AngII in the cycling endometrium. Western blot analysis in the present study
      demonstrated that a considerable amount of APA was present in the secretory phase
      endometrium. ESC in the secretory phase showed strong expression of APA by
      immunohistochemical analysis and of APA mRNA by in situ hybridization. In
      contrast, both APA mRNA and protein were absent in decidual cells. The enzyme
      activity and the biosynthesis of [(35)S]methionine-labeled APA significantly
      decreased during the in vitro decidualization of cultured ESC. These results
      suggest that the perivascular disappearance of APA is a differentiation-specific
      change that occurs along with the decidualization, and that the disappearance of
      APA might accelerate the accumulation of AngII around the vessels.

PMID- 11994382
TI  - Expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, and PDGF
      receptor-alpha and -beta during human testicular development and disease.
AB  - Platelet-derived growth factor (PDGF) plays a critical role in regulating the
      development and functional control of various tissues and has been implicated in
      the pathogenesis of serious diseases, including cancer and atherosclerosis. Given
      the emerging role of PDGF in the development and function of male gonads, we
      compared the expression profiles of the mRNAs of the PDGF A- and B-chains and of
      the PDGF receptor (PDGFR) alpha- and beta-subunits in fetal and adult human
      testis. The immunohistochemical localization of the corresponding proteins in
      fetal, adult, and diseased human testicular tissues was also analyzed. PDGFs and
      PDGFRs mRNAs were readily detected by both Northern analysis and RT-PCR. The
      transcript levels were higher during 16-20 wk gestation, significantly lower at
      24-28 wk, and increased in the adult. An identical pattern of protein expression
      was confirmed by immunohistochemistry, although the cellular localization of the
      PDGF system changes during postnatal development, concomitantly with the
      progression of spermatogenesis. In the testicular samples from patients affected
      by either complete aplasia of germ cells or various grades of spermatogenic
      arrest, the immunohistochemical localization of PDGFs and PDGFRs was different
      from normal, confirming a close connection between germ cells and PDGF system
      distribution. These results indicate that PDGF, through complex interactions,
      could play a leading role in ontogenesis and testicular pathophysiology in
      humans. Finally, the expression of PDGF ligands and receptor proteins in Leydig
      cell tumors suggests a relationship of the PDGF system to tumorigenesis or tumor
      progression in this testicular neoplasm.

PMID- 11994383
TI  - Defective production of interleukin-11 by decidua and chorionic villi in human
      anembryonic pregnancy.
AB  - Previous study demonstrated that IL-11 receptor alpha knockout female mice (IL
      11Ralpha(-/-)) were phenotypically normal but infertile due to defective
      decidualization. However, the role of IL-11 signaling in human reproduction
      remains unclear. This study examined the expression of IL-11, IL-11Ralpha, and
      signal transduction factor glycoprotein 130 in different phases of endometrium
      (six in proliferative phase and four in secretory phase), and the decidua and
      villi of normal pregnancy (NP; n = 25) and anembryonic pregnancy (AP; n = 25) in
      the first trimester (gestational week 7-9). RT-PCR showed IL-11, IL-11Ralpha, and
      glycoprotein 130 mRNA expression in all samples, except the absence of IL-11
      signal in the unstimulated MRC-5 cell and the proliferative phase endometrium.
      Real-time quantitative PCR showed that the relative level of IL-11Ralpha mRNA was
      not significantly different among proliferative phase endometrium (relative
      level; mean +/- SEM, 1.4 +/- 0.5), secretory phase endometrium (1.3 +/- 0.1), or
      decidua from NP or AP (1.7 +/- 0.3 and 1.9 +/- 0.4, respectively), but was
      significantly greater in chorionic villi either from NP or AP (7.6 +/- 1.3 and
      10.6 +/- 1.9, respectively; both P < 0.05, compared with decidua or endometrium).
      No difference of IL-11Ralpha mRNA level was found between NP and AP (1.7 +/- 0.3
      vs. 1.9 +/- 0.4 in deciduas; 7.6 +/- 1.3 vs. 10.6 +/- 1.9 in villi; both P >
      0.05). In situ hybridization localized IL-11Ralpha mRNA expression in
      proliferative phase endometrium (stroma only), secretory phase endometrium
      (stroma and gland), decidua (stroma and gland), and villi (trophoblast and
      stroma). The staining intensities were not distinctly different between different
      groups of samples or between different cell types in a sample. No difference in
      IL-11Ralpha expression was found between NP and AP when either decidua or
      chorionic villi was analyzed. IL-11 mRNA level was not detected in the
      proliferative phase (relative level, 0.0 +/- 0.0), was barely detectable in the
      secretory phase (0.03 +/- 0.02), and was significantly increased in decidua (1.7
      +/- 0.2 and 0.1 +/- 0.1, respectively, for NP and AP) and chorionic villi (13.0
      +/- 2.2 and 0.2 +/- 0.1). In addition, IL-11 mRNA level was higher in NP than in
      AP both in decidua (1.7 +/- 0.2 vs. 0.1 +/- 0.1; P = 0.03) and in villi (13.0 +/-
      2.2 vs. 0.2 +/- 0.1; P < 0.001). Immunohistochemistry study showed that IL-11 was
      nearly absent in endometrium in both phases, but clearly detectable in decidua
      and villi. Consistent with the results of quantitative PCR, the staining
      intensity was stronger in villi and decidua from NP than those from AP. The
      spatial and temporal changes in IL-11 and its receptor observed in this study
      suggest that IL-11 may be produced both by the embryo (predominantly) and the
      decidual cells and exerts its action on chorionic villi and decidua in an
      autocrine or paracrine manner. In the presence of a baseline level of IL
      11Ralpha, IL-11 may subsequently regulate placentation and decidualization for
      the maintenance of a NP. The finding of decreased IL-11 expression in the absence
      of any change in IL-11Ralpha in AP suggests that defective expression of IL-11
      but not IL-11Ralpha may account for certain cases of AP.

PMID- 11994384
TI  - Prolactin induces ERK phosphorylation in epithelial and CD56(+) natural killer
      cells of the human endometrium.
AB  - Functional PRL receptors are expressed in the human endometrium during the
      secretory phase of the menstrual cycle in which PRL stimulates tyrosine
      phosphorylation of Janus kinase 2 and STAT (signal transducer and activator of
      transcription) 1 and 5. In this study, we investigated the effect of PRL on the
      MAPK/ERK pathway in the human endometrium. Human endometrial tissue was collected
      during the mid to late secretory phase of the menstrual cycle. Western blot
      analysis performed on proteins, extracted after up to 30 min culture with PRL,
      demonstrated rapid tyrosine and threonine phosphorylation of ERK 1 and 2 MAPKs.
      The phosphorylation of ERK, in response to PRL, was localized by
      immunohistochemistry to glandular epithelial cells and a subset of stromal cells.
      Using immunofluorescence histochemistry, PRL-induced phosphorylation of ERK in
      the stromal compartment was localized to the uterine-specific CD56(+) natural
      killer (NK) cells. We have demonstrated that the PRL receptor is expressed in
      uterine CD56(+) NK cells in situ by immunofluorescence and in purified decidual
      CD56(+) NK cells by RT-PCR and Western blotting analysis. We have further
      demonstrated phosphorylation of ERK 1 and 2 in cultures of purified uterine
      CD56(+) NK cells, in response to PRL. Our data demonstrate that PRL stimulates
      the ERK pathway in multiple cellular compartments of the human endometrium and
      identify uterine CD56(+) NK cells as novel PRL target cells.

PMID- 11994385
TI  - Regulation of aromatase P450 expression in endometriotic and endometrial stromal
      cells by CCAAT/enhancer binding proteins (C/EBPs): decreased C/EBPbeta in
      endometriosis is associated with overexpression of aromatase.
AB  - In human endometriotic stromal cells, markedly high levels of aromatase P450
      (P450arom) mRNA and promoter II activity are present and can be vigorously
      stimulated by PGE(2) via a cAMP-dependent pathway to give rise to physiologically
      significant estrogen biosynthesis. Stromal cells of eutopic endometrium, on the
      other hand, do not express sufficient levels of P450arom for detectable enzyme
      activity. Because P450arom is up-regulated in the ovaries of CCAAT/enhancer
      binding protein (C/EBP) beta knockout mice and activation of the ovarian-type
      P450arom promoter (II) is responsible for aberrant P450arom expression in
      endometriosis, we sought here to evaluate the possible roles of C/EBP isoforms in
      the regulation of P450arom expression in endometriotic vs. eutopic endometrial
      stromal cells. We previously found that the -517-bp flanking region of promoter
      II contained the critical cis-acting elements for baseline and cAMP (analog)
      induced activity. In this study, we disrupted several potential sequences and
      found that mutations of a -211/-197-bp cAMP-response element (CRE) and a -317/
      304-bp C/EBP binding site abolished both baseline and cAMP-induced promoter II
      activity. Ectopic expression of C/EBPalpha increased both baseline and cAMP
      dependent promoter II activity significantly in endometriotic cells, whereas
      ectopic expression of C/EBPbeta or C/EBPdelta abolished promoter II activity in
      both untreated and cAMP-treated endometriotic stromal cells. Comparable changes
      in promoter II activity were observed using endometrial stromal cells, which
      showed, however, seemingly diminished levels of baseline and cAMP-induced
      promoter II activity in comparison with endometriotic cells. EMSA using a probe
      containing the critical -317/-304-bp C/EBP site upstream of promoter II
      demonstrated a distinct DNA-protein complex in endometriotic, but not in
      endometrial stromal cells. This specific complex, however, could not be altered
      using antibodies against C/EBPalpha, -beta, or -delta. Because CRE is another
      potential DNA motif that can bind C/EBP isoforms, we next used EMSA using a probe
      containing the -211/-197-bp CRE and demonstrated that specific DNA-protein
      complexes contained C/EBPalpha but not C/EBPbeta or C/EBPdelta in endometriotic
      stromal cells. In contrast, C/EBPbeta and C/EBPdelta but not C/EBPalpha were
      detected in DNA-protein complexes using nuclear extracts from endometrial stromal
      cells. Western blotting and immunohistochemistry demonstrated expression of
      C/EBPalpha, -beta, and -delta in human endometriotic and endometrial stroma and
      epithelium. Intriguingly, C/EBPbeta was expressed at increased levels in stromal
      cells of human eutopic endometrium compared with simultaneously biopsied
      endometriotic tissues. We conclude that both -317/-304 and -211/-197-bp elements
      in promoter II are critical for the robust cAMP-dependent induction in
      endometriosis. C/EBPalpha up-regulates, whereas C/EBPbeta and C/EBPdelta inhibit
      P450arom promoter activity via binding primarily to the -211/-197-bp CRE under in
      vitro conditions. In vivo down-regulation of C/EBPbeta in endometriotic stromal
      cells and its up-regulation in endometrial stromal cells may in part account for
      the induction of P450arom expression in endometriosis and its inhibition in
      endometrium.

PMID- 11994386
TI  - In vivo evidence for active matrix metalloproteinases in human endometrium
      supports their role in tissue breakdown at menstruation.
AB  - Human endometrium remodels extensively during each reproductive cycle culminating
      in loss of most functionalis tissue at menstruation. Evidence suggests that
      menstruation results from the action of the matrix metalloproteinases (MMP),
      enzymes secreted in latent forms. MMP activation is thus an important regulatory
      step. It has not been established that MMPs are active within menstrual
      endometrium in vivo. We used in situ zymography to demonstrate active forms of
      MMPs in human endometrium across the normal menstrual cycle. Both gelatinase and
      collagenase activities were detected in most endometrial tissues.
      Semiquantitation demonstrated a substantial and significant increase in both
      gelatinase and collagenase activity in menstrual samples compared with those at
      any other time of the cycle. Gelatinase activity was both associated with cells
      and extracellular. All collagenase activity was extracellular. Immunoreactive MMP
      2 and MMP-9 colocalized with active gelatinase, although much immunoreactive
      gelatinase was inactive. Some gelatinase activity colocalized with CD45(+)
      leukocytes. Menstruation is initiated at discrete foci, and active MMPs were
      similarly at foci within the tissue. This is the first in vivo evidence for
      increased active MMPs in menstrual endometrium compared with other stages of the
      cycle. These findings position the MMPs for a critical role in the matrix
      degradation at menstruation.

PMID- 11994387
TI  - Stimulation of adipogenesis, peroxisome proliferator-activated receptor-gamma
      (PPARgamma), and thyrotropin receptor by PPARgamma agonist in human orbital
      preadipocyte fibroblasts.
AB  - The symptoms and signs of Graves' ophthalmopathy (GO) result from both an
      accumulation of hydrated hyaluronan in the orbital muscles and connective tissues
      and an expansion of the orbital adipose tissues. Recent studies have suggested a
      link between the stimulation of adipogenesis within the orbit in GO and the
      expression in these tissues of TSH receptor (TSHR), the putative orbital
      autoantigen. To further investigate this association, we treated orbital
      fibroblasts from patients with GO with rosiglitazone, a thiazolidinedione agonist
      of the PPARgamma receptor that stimulates adipocyte differentiation. We found
      this compound to be a potent stimulator of functional TSHR expression as well as
      TSHR and PPARgamma mRNA levels in differentiated cultures. In addition,
      rosiglitazone treatment stimulated recruitment and differentiation of a subset of
      cells within these cultures into mature lipid-laden adipocytes. These results
      suggest that TSHR expression in GO orbital preadipocyte fibroblasts is linked to
      adipogenesis, and that ligation of the PPARgamma receptor results in
      differentiation of these cells. It is possible that endogenous PPARgamma ligands
      play a role in stimulating orbital adipogenesis in GO, and that future treatments
      may be aimed at antagonism of various components of the PPARgamma signaling
      system.

PMID- 11994388
TI  - Identification and regulation of the IGFBP-4 protease and its physiological
      inhibitor in human trophoblasts and endometrial stroma: evidence for paracrine
      regulation of IGF-II bioavailability in the placental bed during human
      implantation.
AB  - The IGF family plays an important role in implantation and placental physiology.
      IGF-II is abundantly expressed by placental trophoblasts, and IGF binding protein
      (IGFBP)-4, a potent inhibitor of IGF actions, is the second most abundant IGFBP
      in the placental bed, expressed exclusively by the maternal decidua. Proteolysis
      of IGFBP-4 results in decreased affinity for IGF peptides, thereby enhancing IGF
      actions. In the current study, we have identified the IGFBP-4 protease and its
      inhibitor in human trophoblast and decidualized endometrial stromal cell
      cultures, and we have investigated their regulation in an effort to understand
      control of IGF-II bioavailability at the placental-decidual interface in human
      implantation. IGFBP-4 protease activity was detected in conditioned media (CM)
      from human trophoblasts and decidualized endometrial stromal cells using (125)I
      IGFBP-4 substrate. Identification of the IGFBP-4 protease as pregnancy-associated
      plasma protein-A (PAPP-A) was confirmed by specific immunoinhibition and
      immunodepletion of the IGFBP-4 protease activity with specific PAPP-A antibodies.
      The IGFBP-4 protease activity was IGF-II-dependent in trophoblast CM. In
      decidualized stromal CM, PAPP-A/IGFBP-4 protease activity was also IGF-II
      dependent, but was evident only when IGF-II was added in molar excess of the
      predominant IGFBP in decidualized stromal cell CM, IGFBP-1, supporting
      bioavailable IGF-II as a key cofactor of IGFBP-4 proteolysis by PAPP-A. Cultured
      first and second trimester human trophoblasts (n = 5) secreted PAPP-A into CM
      with mean +/- SEM levels of 172.4 +/- 32.8 mIU/liter.10(5) cells, determined by
      specific ELISA. PAPP-A in trophoblast CM (n = 3) and did not change in the
      presence of IGF-II (1-100 ng/ml). Cultured human endometrial stromal cells (n =
      4) secreted low levels of PAPP-A (6.25 +/- 3.6 mIU/liter.10(5) cells). A
      physiological inhibitor of PAPP-A, the proform of eosinophil major basic protein
      (proMBP), was detected in trophoblast CM at levels of 1853 +/- 308
      mIU/liter.10(5) cells, determined by specific ELISA, and was nearly undetectable
      in CM of human endometrial stromal cells. Upon in vitro decidualization of
      endometrial stromal cells with progesterone, PAPP-A levels in CM increased nearly
      9-fold without a concomitant change in proMBP. In contrast to the experiments
      with trophoblasts, IGF-II and the IGF analogues, Leu(27) IGF-II, and Des (1-6)
      IGF-II, resulted in a dose-dependent decrease of PAPP-A levels in decidualized
      endometrial stromal CM by 70-90%, and a dose-dependent increase in proMBP of 14-
      to 41-fold. The data demonstrate conclusively that the IGF-II-dependent IGFBP-4
      protease of human trophoblast and decidual origin is PAPP-A. Furthermore, the
      differential regulation of decidual PAPP-A and proMBP by insulin-like peptides
      supports a role for trophoblast-derived IGF-II as a paracrine regulator of these
      maternal decidual products that have the potential to regulate IGF-II
      bioavailability at the trophoblast-decidual interface. Overall, the data
      underscore potential roles for a complex family of enzyme (PAPP-A), substrate
      (IGFBP-4), inhibitor (proMBP), and cofactor (IGF-II) in the placental bed during
      human implantation.

PMID- 11994389
TI  - Cosecretion of estrogen and inhibin B by a feminizing adrenocortical adenoma:
      impact on gonadotropin secretion.
AB  - We describe the first reported case of a feminizing adrenocortical adenoma
      cosecreting estrogens and inhibin B. A 39-yr-old man, with no previous history of
      disease and free of treatment, complained of gynecomastia without any clinical
      abnormality. Plasma E2 and T were 496 pmol/liter and 8.7 nmol/liter,
      respectively. Testicular echography was normal, and abdominal computed tomography
      scan showed a 28-mm right adrenal tumor. hCG (5000 IU, im) induced a rise in
      plasma T levels (20.7 nmol/liter) without any change in plasma E2 levels. Basal
      plasma LH and FSH levels were undetectable. GnRH (100 microg, i.v.) induced an
      increase in plasma LH levels without a change in plasma FSH levels. The mean
      plasma inhibin B level was 330 +/- 45 pg/ml (normal range, 94-327). Pulsatile
      GnRH administration (20 microg/pulse every 90 min for 3 d) stimulated LH
      secretion, whereas FSH secretion remained blunted. The patient underwent surgery
      to remove a 12-g adrenal adenoma. Six months later, plasma E2 and T levels were
      normalized. LH showed a spontaneous pulsatile pattern, and the mean plasma FSH
      level was 4.8 U/liter. The secretion of both gonadotropins was stimulated during
      a pulsatile GnRH administration performed in the same manner as before surgery.
      The mean plasma inhibin B level was 210 +/- 25 pg/ml. Immunohistochemical studies
      revealed the presence of aromatase in clusters of tumor cells. Incubation of
      tumor sections with anti-beta(B)-inhibin antibody revealed intense staining in
      groups of cells that were also labeled with anti-alpha-inhibin antibody. These
      data show that the tumor cosecreted E2 and inhibin B, which were both responsible
      for inhibition of gonadotropin secretion. Tumor secretions appeared to be much
      more potent in suppressing FSH than LH levels.

PMID- 11994390
TI  - Induction of hepatocyte growth factor in stromal cells by tumor-derived basic
      fibroblast growth factor enhances growth and invasion of endometrial cancer.
AB  - Tumor progression is often regulated through interactions between carcinoma cells
      and host stromal cells. In this study of endometrial cancer, we investigated one
      mechanism potentially involved in hepatocyte growth factor (HGF)-mediated cancer
      stromal interactions. Endometrial cancer cells (HEC-1 and ISHIKAWA) expressed the
      c-met receptor, but HGF did not. HGF, however, did stimulate the proliferation
      and invasion of these cells. The HGF gene was expressed in stromal cells, which
      had been separated from primary cultures of endometrial cancers, 6.4 times more
      than in isolated normal endometrial stromal cells. Immunohistochemical staining
      revealed immunoreactive HGF in cancer stromal cells, the staining intensity being
      more pronounced in cancer tissue than in normal endometrium. The conditioned
      medium from normal epithelial cells and cancer cell lines induced HGF production
      in normal stromal cells. We identified basic fibroblast growth factor as an HGF
      inducer derived from endometrial cancer cell lines. Basic fibroblast growth
      factor derived from tumor cells may induce HGF in endometrial stromal cells,
      whereas stromal cell-derived HGF leads to the invasive growth of carcinoma cells.
      These interactions, mediated by HGF and HGF inducers, may play a significant role
      in the progression of endometrial cancer.

PMID- 11994391
TI  - Induction of adipocyte differentiation by a thiazolidinedione in cultured,
      subepidermal, fibroblast-like cells of an infant with congenital generalized
      lipodystrophy.
AB  - Congenital generalized lipodystrophy (CGL) is characterized by the absence of
      adipose tissue from birth due to a hypothetical differentiation block. The
      genetic causes of CGL are still not completely understood. Subepidermal,
      fibroblast-like cells were prepared from the sc tissue of an infant with CGL.
      Preadipocytes from sc adipose tissue and foreskin fibroblasts from three healthy
      patients, respectively, were used as controls. Adipose differentiation was
      induced in cultured cells by exposure to 10 nM insulin, 200 pM T(3), 1 microM
      cortisol, and 2 microM rosiglitazone. Under these conditions 42% of the
      subepidermal, fibroblast-like CGL cells developed into mature adipocytes.
      Adipogenic differentiation was dependent on rosiglitazone. The differentiation
      rate was comparable in cultures of preadipocytes from control patients maintained
      under the same conditions (53%, 38%, and 20%). In contrast, foreskin fibroblasts
      did not differentiate into adipocytes. Morphological changes in CGL cells during
      differentiation were associated with the expression of fat cell-specific mRNAs
      (PPARgamma, leptin, and glut-4). In addition, these cells revealed characteristic
      features of mature adipocytes, such as lipogenesis or leptin secretion. Taken
      together, we show that adipocyte precursor cells were present in subepidermal
      tissue of a patient with CGL and were able to differentiate into adipocytes in
      the presence of a thiazolidinedione. These findings strongly support clinical
      trials with thiazolidinediones in patients with CGL.

PMID- 11994393
TI  - Low dose leptin administration reverses effects of sustained weight-reduction on
      energy expenditure and circulating concentrations of thyroid hormones.
AB  - Maintenance of a reduced body weight is associated with decreased 24-hour energy
      expenditure, and decreased circulating concentrations of leptin and thyroid
      hormones. To determine whether these adaptive metabolic and endocrine changes are
      partly leptin-mediated, we measured body composition, aspects of energy
      expenditure, and circulating concentrations of leptin and thyroid hormones in 4
      subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced
      body weight; and 3.) During a 5-week period at 10% reduced body weight while
      receiving twice per day leptin injections that restored 8 AM circulating leptin
      concentrations to those seen at usual body weight. During maintenance of a 10%
      reduced body weight, circulating T3, T4, and leptin concentrations were
      decreased. All of these endocrine changes were reversed by administration of
      "replacement" doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle
      changes in body composition associated with leptin administration, were used to
      calculate the net change in stored calories and in 24-hour energy expenditure.
      Total energy expenditure increased in all subjects during r-metHuLeptin
      administration. These data indicate that decrease leptin concentrations resulting
      from loss of fat mass account for some aspects of the endocrine/metabolic
      phenotype associated with the weight-reduced state.

PMID- 11994394
TI  - Serum adiponectin and leptin levels in patients with lipodystrophies.
AB  - Lipodystrophies are characterized by selective but variable loss of body fat and
      metabolic complications of insulin resistance. We hypothesized that reduced
      synthesis and secretion of adipocyte-specific proteins may be related to the
      metabolic complications of lipodystrophy. Therefore, we compared fasting serum
      concentrations of adiponectin and leptin, in 18 patients with congenital
      generalized lipodystrophy (CGL), 11 with acquired generalized lipodystrophy
      (AGL), 46 with familial partial lipodystrophy-Dunnigan variety (FPLD) and 18 with
      acquired partial lipodystrophy (APL) and studied their relationship to metabolic
      parameters. Patients with CGL and AGL had markedly reduced serum adiponectin
      levels compared to those with FPLD and APL (median [range]: 1.5 [0.4-7.5], 3.2
      [0.6-7.7], 6.9 [1.9-23.2] and 7.9 [3.1-13.3] microg/mL, respectively, p <
      0.0001); the same trend was noted for serum leptin levels (0.63 [0.05-3.7], 2.18
      [0.05-11.30], 2.86 [0.23-9.00] and 6.24 [1.21-10.4] ng/mL, respectively, p <
      0.0001). Serum adiponectin levels correlated negatively with fasting serum
      triglycerides (r = -0.6, p < 0.001) and insulin levels (r = -0.5, p < 0.0001) and
      positively with serum high-density lipoprotein cholesterol levels (r = 0.5, p <
      0.001). Serum adiponectin levels were lower in patients with diabetes compared to
      non-diabetic subjects (3.0 vs. 7.1 microg/mL, p < 0.001). Our results indicate
      that serum adiponectin and leptin levels are extremely low in patients with
      generalized lipodystrophies and may be related to severe insulin resistance and
      its metabolic complications in lipodystrophies.

PMID- 11994395
TI  - Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP
      kinase in thyroid cancer cells.
AB  - The development of distant metastasis is the most important predictor of death
      from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene
      whose product, metastin, was recently identified as the endogenous agonist for a
      novel Gq/11 coupled receptor (metastin receptor). The expression and functional
      consequences of metastin and the metastin receptor have not been evaluated in
      thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs
      and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas
      (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways
      activated by metastin in ARO thyroid cancer cells that express the metastin
      receptor endogenously. Paired normal and tumor samples were available for 4 PC
      and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA,
      2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not
      expressed in any normal thyroid or benign FA samples, and was expressed in only a
      minority (2/10) of FC samples. However, the receptor was expressed in the
      majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of
      metastin receptor were detected in all four PCs compared to adjacent normal
      tissue. Incubation levels of metastin receptor were detected in all four PCs
      compared to adjacent normal tissue. Incubation of metastin receptor expressing
      ARO thyroid cancer cells with metastin resulted in activation of ERK, but not
      Akt. Taken together, these data suggest a potential role for metastin and/or
      metastin receptors in modulating the biological behavior of thyroid cancers.

PMID- 11994396
TI  - Peroxisome proliferator activated receptor gamma expression is reduced in the
      colonic mucosa of acromegalic patients.
AB  - Acromegalic patients have an increased prevalence of colonic polyps, due to the
      elevated serum insulin like growth factor (IGF)-I levels. The mechanisms
      underlying this process are poorly understood. Peroxisome proliferator activated
      receptor (PPAR)gamma, a nuclear receptor that regulates adipocyte
      differentiation, is highly expressed in the human colonic mucosa, where it
      induces growth inhibition and cell differentiation. In the present study we
      evaluated the expression of PPARgamma in the bioptic samples of colonic mucosa
      from 22 patients with acromegaly (Acro) and 13 normal subjects (CONTROLS) matched
      for age and sex. Among Acro patients, 10 had active, untreated disease
      (AcroUntr), 6 were in remission after surgery (AcroRem), and 6 had active disease
      under treatment with somatostatin analogs (AcroSMSa). Serum GH and IGF-I (mean +/
      SD) levels were as follows: AcroUntr: GH, 36 +/- 40 microg/l; IGF-I, 769 +/- 298
      microg/l; AcroRem: GH, 1.0 +/- 1.3 microg/l; IGF-I, 248 +/- 96 microg/l;
      AcroSMSa: GH, 7.8 +/- 12 microg/l; IGF-I, 429 +/- 221 microg/l; CONTROLS: GH, 0.8
      +/- 0.7 microg/l; IGF-I, 203 +/- 67 microg/l. In the CONTROLS the level of
      expression of PPARgamma mRNA was 15230 +/- 891 transcripts. Patients with
      AcroUntr had 2750 +/- 688 transcripts of PPARgamma. (p < 0.0001) vs. CONTROLS);
      patients AcroSMSa had 4629 +/- 1286 transcripts of PPARgamma. (p = NS vs
      AcroUntr, p = 0.0002 vs. CONTROLS); patients with AcroRem had 8261 +/- 2481
      transcripts of PPARgamma (p = 0.008 vs. AcroUntr, p = NS vs. AcroSMSa, p = 0.007
      vs. CONTROLS). A significant inverse correlation was found between serum IGF-I
      concentrations and the level of expression of PPARgamma (r = 0.43, p = 0.03). In
      conclusion, patients with active Acro have a reduced expression of PPARgamma in
      the colonic mucosa, which appears be related to the increased serum IGF-I levels
      and might lead to an increased prevalence of colonic polyps.

PMID- 11994397
TI  - Increased resistin gene and protein expression in human abdominal adipose tissue.
AB  - Resistin, a novel signalling molecule isolated in mice has been suggested to be
      the putative hormone thought to link obesity with type 2 diabetes. The aim of
      this study was to examine resistin protein expression in human adipose tissue
      depots and resistin secretion in isolated adipose cells, to characterize resistin
      expression in human adipose tissue. Both resistin mRNA and protein expression
      were analysed from human adipose tissue (n = 5 adipose tissue samples: abdominal
      subcutaneous (Sc) n = 19, abdominal omental adipose tissue (Om) n = 10, thigh n =
      9, breast n = 7). Resistin protein expression levels were similar in both the
      abdominal Sc and Om adipose tissue depots, and expression in abdominal fat depots
      were increased compared with thigh (p < 0.001) and breast tissue depots (p <
      0.001). These findings were consistent with the mRNA expression studies. Resistin
      was secreted from both pre-adipocytes and adipocytes cells. Thus, resistin
      resides within isolated adipose cells and is expressed and secreted in human
      adipose tissue. In conclusion, this study confirms the expression of resistin in
      human adipose tissue and increased expression in abdominal fat, this suggests a
      potential role in linking central obesity to type 2 diabetes and/or
      cardiovascular disease.

PMID- 11994398
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 11994399
TI  - SREBPs: activators of the complete program of cholesterol and fatty acid
      synthesis in the liver.

PMID- 11994400
TI  - Series introduction. JAK-STAT signaling in human disease.

PMID- 11994401
TI  - Stat proteins and oncogenesis.

PMID- 11994402
TI  - What does Stat3 do?

PMID- 11994403
TI  - NO solutions?

PMID- 11994404
TI  - Beta cell expression of IGF-I leads to recovery from type 1 diabetes.
AB  - Patients with type 1 diabetes are identified after the onset of the disease, when
      beta cell destruction is almost complete. beta cell regeneration from islet cell
      precursors might reverse this disease, but factors that can induce beta cell
      neogenesis and replication and prevent a new round of autoimmune destruction
      remain to be identified. Here we show that expression of IGF-I in beta cells of
      transgenic mice (in both C57BL/6-SJL and CD-1 genetic backgrounds) counteracts
      cytotoxicity and insulitis after treatment with multiple low doses of
      streptozotocin (STZ). STZ-treated nontransgenic mice developed high hyperglycemia
      and hypoinsulinemia, lost body weight, and died. In contrast, STZ-treated C57BL/6
      SJL transgenic mice showed mild hyperglycemia for about 1 month, after which they
      normalized glycemia and survived. After STZ treatment, all CD-1 mice developed
      high hyperglycemia, hypoinsulinemia, polydipsia, and polyphagia. However, STZ
      treated CD-1 transgenic mice gradually normalized all metabolic parameters and
      survived. beta cell mass increased in parallel as a result of neogenesis and beta
      cell replication. Thus, our results indicate that local expression of IGF-I in
      beta cells regenerates pancreatic islets and counteracts type 1 diabetes,
      suggesting that IGF-I gene transfer to the pancreas might be a suitable therapy
      for this disease.

PMID- 11994405
TI  - Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for
      the pseudophosphatase Sbf1.
AB  - Pseudophosphatases display extensive sequence similarities to phosphatases but
      harbor amino acid alterations in their active-site consensus motifs that render
      them catalytically inactive. A potential role in substrate trapping or docking
      has been proposed, but the specific requirements for pseudophosphatases during
      development and differentiation are unknown. We demonstrate here that Sbf1, a
      pseudophosphatase of the myotubularin family, is expressed at high levels in
      seminiferous tubules of the testis, specifically in Sertoli's cells,
      spermatogonia, and pachytene spermatocytes, but not in postmeiotic round
      spermatids. Mice that are nullizygous for Sbf1 exhibit male infertility
      characterized by azoospermia. The onset of the spermatogenic defect occurs in the
      first wave of spermatogenesis at 17 days after birth during the synchronized
      progression of pachytene spermatocytes to haploid spermatids. Vacuolation of the
      Sertoli's cells is the earliest observed phenotype and is followed by reduced
      formation of spermatids and eventual depletion of the germ cell compartment in
      older mice. The nullizygous phenotype in conjunction with high-level expression
      of Sbf1 in premeiotic germ cells and Sertoli's cells is consistent with a crucial
      role for Sbf1 in transition from diploid to haploid spermatocytes. These studies
      demonstrate an essential role for a pseudophosphatase and implicate signaling
      pathways regulated by myotubularin family proteins in spermatogenesis and germ
      cell differentiation.

PMID- 11994406
TI  - Parathyroid hormone is essential for normal fetal bone formation.
AB  - Parathyroid hormone (PTH) is a potent pharmacologic inducer of new bone
      formation, but no physiologic anabolic effect of PTH on adult bone has been
      described. We investigated the role of PTH in fetal skeletal development by
      comparing newborn mice lacking either PTH, PTH-related peptide (PTHrP), or both
      peptides. PTH-deficient mice were dysmorphic but viable, whereas mice lacking
      PTHrP died at birth with dyschondroplasia. PTH-deficient mice uniquely
      demonstrated diminished cartilage matrix mineralization, decreased
      neovascularization with reduced expression of angiopoietin-1, and reduced
      metaphyseal osteoblasts and trabecular bone. Compound mutants displayed the
      combined cartilaginous and osseous defects of both single mutants. These results
      indicate that coordinated action of both PTH and PTHrP are required to achieve
      normal fetal skeletal morphogenesis, and they demonstrate an essential function
      for PTH at the cartilage-bone interface. The effect of PTH on fetal osteoblasts
      may be relevant to its postnatal anabolic effects on trabecular bone.

PMID- 11994407
TI  - Intracerebral transplantation of mesenchymal stem cells into acid
      sphingomyelinase-deficient mice delays the onset of neurological abnormalities
      and extends their life span.
AB  - Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders
      resulting from loss of acid sphingomyelinase (ASM) activity. We have used a
      knockout mouse model of NPD (ASMKO mice) to evaluate the effects of direct
      intracerebral transplantation of bone marrow-derived mesenchymal stem cells
      (MSCs) on the progression of neurological disease in this disorder. MSCs were
      transduced with a retroviral vector to overexpress ASM and were injected into the
      hippocampus and cerebellum of 3-week-old ASMKO pups. Transplanted cells migrated
      away from the injection sites and survived at least 6 months after
      transplantation. Seven of 8 treated mice, but none of the untreated controls,
      survived for > or = 7 months after transplant. Survival times were greater in sex
      matched than in sex-mismatched transplants. Transplantation significantly delayed
      the Purkinje cell loss that is characteristic of NPD, although the protective
      effect declined with distance from the injection site. Overall ASM activity in
      brain homogenates was low, but surviving Purkinje cells contained the
      retrovirally expressed human enzyme, and transplanted animals showed a reduction
      in cerebral sphingomyelin. These results reveal the potential of treating
      neurodegenerative lysosomal storage disorders by intracerebral transplantation of
      bone marrow-derived MSCs.

PMID- 11994408
TI  - Pdx1 restores beta cell function in Irs2 knockout mice.
AB  - The homeodomain transcription factor Pdx1 is required for pancreas development,
      including the differentiation and function of beta cells. Mutations in Pdx1 or
      upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes
      (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the
      insulin/Igf signaling system mediates peripheral insulin action and pancreatic
      beta cell growth and function. To investigate whether beta cell failure in Irs2(
      /-) mice might be related to dysfunction of MODY-related transcription factors,
      we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. Before
      the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it
      was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not
      develop diabetes. Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between
      8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn
      Irs2(-/-) mice. By contrast, transgenic expression of Pdx1 restored beta cell
      mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout
      life, as these mice survived for at least 20 months without diabetes. Our results
      suggest that dysregulation of Pdx1 might represent a common link between ordinary
      type 2 diabetes and MODY.

PMID- 11994409
TI  - Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6-specific
      IgA mAb.
AB  - Rotaviruses are the leading cause of severe diarrheal disease in young children.
      Intestinal mucosal IgA responses play a critical role in protective immunity
      against rotavirus reinfection. Rotaviruses consist of three concentric capsid
      layers surrounding a genome of 11 segments of double-stranded RNA. The outer
      layer proteins, VP4 and VP7, which are responsible for viral attachment and
      entry, are targets for protective neutralizing antibodies. However, IgA mAb's
      directed against the intermediate capsid protein VP6, which do not neutralize the
      virus, have also been shown to protect mice from rotavirus infection and clear
      chronic infection in SCID mice. We investigated whether the anti-VP6 IgA (7D9)
      mAb could inhibit rotavirus replication inside epithelial cells and found that
      7D9 acted at an early stage of infection to neutralize rotavirus following
      antibody lipofection. Using electron cryomicroscopy, we determined the three
      dimensional structure of the virus-antibody complex. The attachment of 7D9 IgA to
      VP6 introduces a conformational change in the VP6 trimer, rendering the particle
      transcriptionally incompetent and preventing the elongation of initiated
      transcripts. Based on these observations, we suggest that anti-VP6 IgA antibodies
      confers protection in vivo by inhibiting viral transcription at the start of the
      intracellular phase of the viral replication cycle.

PMID- 11994410
TI  - Systemic inflammation in glucocerebrosidase-deficient mice with minimal
      glucosylceramide storage.
AB  - Gaucher disease, the most common lysosomal storage disease, is caused by a
      deficiency of glucocerebrosidase resulting in the impairment of glucosylceramide
      degradation. The hallmark of the disease is the presence of the Gaucher cell, a
      macrophage containing much of the stored glucosylceramide found in tissues, which
      is believed to cause many of the clinical manifestations of the disease. We have
      developed adult mice carrying the Gaucher disease L444P point mutation in the
      glucocerebrosidase (Gba) gene and exhibiting a partial enzyme deficiency. The
      mutant mice demonstrate multisystem inflammation, including evidence of B cell
      hyperproliferation, an aspect of the disease found in some patients. However, the
      mutant mice do not accumulate large amounts of glucosylceramide or exhibit
      classic Gaucher cells in tissues.

PMID- 11994411
TI  - Endogenous regulation of a therapeutic transgene restores homeostasis in
      arthritic joints.
AB  - The treatment of chronic inflammatory diseases is complicated by their
      unpredictable, relapsing clinical course. Here, we describe a new strategy in
      which an inflammation-regulated therapeutic transgene is introduced into the
      joints to prevent recurrence of arthritis. To this end, we designed a recombinant
      adenoviral vector containing a two-component, inflammation-inducible promoter
      controlling the expression of human IL-10 (hIL-10) cDNA. When tested in vitro,
      this system had a low-level basal activity and was activated four to five orders
      of magnitude by various inflammatory stimuli, including TNF-alpha, IL-1 beta, IL
      6, and LPS. When introduced in joints of rats with recurrent streptococcal cell
      wall-induced arthritis, the IL-10 transgene was induced in parallel with disease
      recurrence and effectively prevented the influx of inflammatory cells and the
      associated swelling of the joints. Levels of inflammation-inducible hIL-10
      protein within the joints correlated closely with the severity of recurrence. An
      endogenously regulated therapeutic transgene can thus establish negative feedback
      and restore homeostasis in vivo while minimizing host exposure to the recombinant
      drug.

PMID- 11994412
TI  - Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T
      lymphocytes in primary biliary cirrhosis.
AB  - While the pathologic mechanisms responsible for organ-specific tissue damage in
      primary biliary cirrhosis (PBC) remain an enigma, it has been suggested that the
      pathology is mediated by autoreactive T cells infiltrating the intrahepatic bile
      ducts. Previously, we have documented that there is 100-fold enrichment in the
      frequency of CD4(+) autoreactive T cells in the liver that are specific for
      peptides encoded by the E2 components of the pyruvate dehydrogenase complexes
      (PDC-E2). We have also recently characterized the first MHC class I-restricted
      epitope for PDC-E2, namely amino acid 159-167, a region very similar to the
      epitope recognized by MHC class II-restricted CD4(+) cells and by autoantibodies.
      The effector functions of these PDC-E2(159-167)-specific CD8(+) cytotoxic T
      lymphocytes (CTLs) are not well understood. We have taken advantage of tetramer
      technology and report herein that there is tenfold increase in the frequency of
      PDC-E2(159-167)-specific CTLs in the liver as compared with the blood in PBC. In
      addition, the precursor frequency of the CTLs in blood was significantly higher
      in early-stage PBC. Of interest was the fact that, upon stimulation with the
      peptide, the response of PDC-E2(159-167) tetramer-positive cells is heterogeneous
      with respect to IFN-gamma synthesis. These data, we believe for the first time,
      document the enrichment of autoantigen-specific CD8(+) T cells in the PBC liver,
      suggesting that CD8(+) T cells play a significant role in the immunopathogenesis
      of PBC.

PMID- 11994413
TI  - Evidence for in vivo transport of bioactive nitric oxide in human plasma.
AB  - Although hitherto considered as a strictly locally acting vasodilator, results
      from recent clinical studies with inhaled nitric oxide (NO) indicate that NO can
      exert effects beyond the pulmonary circulation. We therefore sought to
      investigate potential remote vascular effects of intra-arterially applied aqueous
      NO solution and to identify the mechanisms involved. On bolus application of NO
      into the brachial artery of 32 healthy volunteers, both diameter of the
      downstream radial artery and forearm blood flow increased in a dose-dependent
      manner. Maximum dilator responses were comparable to those after stimulation of
      endogenous NO formation with acetylcholine and bradykinin. Response kinetics and
      pattern of NO decomposition suggested that despite the presence of hemoglobin
      containing erythrocytes, a significant portion of NO was transported in its
      unbound form. Infusion of NO (36 micromol/min) into the brachial artery increased
      levels of plasma nitroso species, nitrite, and nitrate in the draining
      antecubital vein (by < 2-fold, 30-fold, and 4-fold, respectively), indicative of
      oxidative and nitrosative chemistry. Infused N-oxides were inactive as
      vasodilators whereas S-nitrosoglutathione dilated conduit and resistance
      arteries. Our results suggest that NO can be transported in bioactive form for
      significant distances along the vascular bed. Both free NO and plasma nitroso
      species contribute to the dilation of the downstream vasculature.

PMID- 11994414
TI  - Enhanced allostimulatory activity of host antigen-presenting cells in old mice
      intensifies acute graft-versus-host disease.
AB  - Older bone marrow transplantation (BMT) recipients are at heightened risk for
      acute graft-versus-host disease (GVHD) after allogeneic BMT, but the causes of
      this association are poorly understood. Using well-characterized murine BMT
      models we have explored the mechanisms of increased GVHD in older mice. GVHD
      mortality, morbidity, and pathologic and biochemical indices were all worse in
      old recipients. Donor T cell responses were significantly increased in old
      recipients both in vivo and in vitro when stimulated by antigen-presenting cells
      (APCs) from old mice, which also secreted more TNF-alpha and IL-12 after LPS
      stimulation. In a B6 --> B6D2F1 model, CD4(+) donor T cells but not CD8(+) T
      cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs
      in GVHD using B6D2F1 BM chimeras created with either old or young BM. Four months
      after chimera creation, allogeneic BMT from B6 donors caused significantly worse
      GVHD in old BM chimeras. APCs from these mice also stimulated greater responses
      from allogeneic cells in vitro. These data demonstrate a hitherto unsuspected
      mechanism of amplified donor T cell responses by aged allogeneic host APCs that
      increases acute GVHD in aged recipients in this BMT model.

PMID- 11994415
TI  - Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in
      chronic hepatitis B virus infection.
AB  - Deletion, anergy, and a spectrum of functional impairments can affect virus
      specific CD8 cells in chronic viral infections. Here we characterize a low
      frequency population of CD8 cells present in chronic hepatitis B virus (HBV)
      infection which survive in the face of a high quantity of viral antigen. Although
      they do not appear to exert immunological pressure in vivo, these CD8 cells are
      not classically "tolerant" since they proliferate, lyse, and produce antiviral
      cytokines in vitro. They are characterized by altered HLA/peptide tetramer
      reactivity, which is not explained by TCR down-regulation or reduced functional
      avidity and which can be reversed with repetitive stimulation. CD8 cells with
      altered tetramer binding appear to have a specificity restricted to envelope
      antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell
      dysfunction are differentially regulated according to the antigenic form and
      presentation of individual viral antigens.

PMID- 11994416
TI  - Vav1 transduces T cell receptor signals to the activation of phospholipase C
      gamma1 via phosphoinositide 3-kinase-dependent and -independent pathways.
AB  - Vav1 is a signal transducing protein required for T cell receptor (TCR) signals
      that drive positive and negative selection in the thymus. Furthermore, Vav1
      deficient thymocytes show greatly reduced TCR-induced intracellular calcium flux.
      Using a novel genetic system which allows the study of signaling in highly
      enriched populations of CD4(+)CD8(+) double positive thymocytes, we have studied
      the mechanism by which Vav1 regulates TCR-induced calcium flux. We show that in
      Vav1-deficient double positive thymocytes, phosphorylation, and activation of
      phospholipase C-gamma1 (PLCgamma1) is defective. Furthermore, we demonstrate that
      Vav1 regulates PLCgamma1 phosphorylation by at least two distinct pathways.
      First, in the absence of Vav1 the Tec-family kinases Itk and Tec are no longer
      activated, most likely as a result of a defect in phosphoinositide 3-kinase
      (PI3K) activation. Second, Vav1-deficient thymocytes show defective assembly of a
      signaling complex containing PLCgamma1 and the adaptor molecule Src homology 2
      domain-containing leukocyte phosphoprotein 76. We show that this latter function
      is independent of PI3K.

PMID- 11994417
TI  - Vav1 is a component of transcriptionally active complexes.
AB  - The importance of the hematopoietic protooncogene Vav1 in immune cell function is
      widely recognized, although its regulatory mechanisms are not completely
      understood. Here, we examined whether Vav1 has a nuclear function, as past
      studies have reported its nuclear localization. Our findings provide a definitive
      demonstration of Vav1 nuclear localization in a receptor stimulation-dependent
      manner and reveal a critical role for the COOH-terminal Src homology 3 (SH3)
      domain and a nuclear localization sequence within the pleckstrin homology domain.
      Analysis of DNA-bound transcription factor complexes revealed nuclear Vav1 as an
      integral component of transcriptionally active nuclear factor of activated T
      cells (NFAT)- and nuclear factor (NF)kappaB-like complexes, and the COOH-terminal
      SH3 domain as being critical in their formation. Thus, we describe a novel
      nuclear role for Vav1 as a component and facilitator of NFAT and NFkappaB-like
      transcriptional activity.

PMID- 11994418
TI  - The transcription factor T-bet regulates mucosal T cell activation in
      experimental colitis and Crohn's disease.
AB  - The balance between pro and antiinflammatory cytokines secreted by T cells
      regulates both the initiation and perpetuation of inflammatory bowel diseases
      (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)
      4 and transforming growth factor (TGF)-beta activity controls chronic intestinal
      inflammation. However, the molecular pathways that evoke these responses are not
      well understood. Here, we describe a critical role for the transcription factor T
      bet in controlling the mucosal cytokine balance and clinical disease. We studied
      the expression and function of T-bet in patients with IBD and in mucosal T cells
      in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal
      inflammation by taking advantage of mice that lack T-bet and retroviral
      transduction techniques, respectively. Whereas retroviral transduction of T-bet
      in CD62L(+) CD4(+) T cells exacerbated colitis in reconstituted SCID mice, T-bet
      deficient T cells failed to induce colitis in adoptive transfer experiments
      suggesting that overexpression of T-bet is essential and sufficient to promote
      Th1-mediated colitis in vivo. Furthermore, T-bet-deficient CD62L(-) CD4(+) T
      cells showed enhanced protective functions in Th1-mediated colitis and exhibited
      increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell
      activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta
      responses and the development of chronic intestinal inflammation in T cell
      mediated colitis. Furthermore, TGF-beta was found to suppress T-bet expression
      suggesting a reciprocal relationship between TGF-beta and T-bet in mucosal T
      cells. In summary, our data suggest a key regulatory role of T-bet in the
      pathogenesis of T cell-mediated colitis. Specific targeting of this pathway may
      be a promising novel approach for the treatment of patients with Crohn's disease
      and other autoimmune diseases mediated by Th1 T lymphocytes.

PMID- 11994419
TI  - Hematopoietic stem cells are uniquely selective in their migratory response to
      chemokines.
AB  - Although hematopoietic stem cell (HSC) migration into and out of sites of active
      hematopoiesis is poorly understood, it is a critical process that underlies
      modern clinical stem cell transplantation and may be important for normal
      hematopoietic homeostasis. Given the established roles of chemotactic cytokine
      (chemokine)-directed migration of other leukocyte subsets, the migration of
      murine HSC to a large panel of CC and CXC chemokines was investigated. HSC
      migrated only in response to stromal derived factor-1alpha, the ligand for the
      CXC chemokine receptor 4 (CXCR4). CXCR4 expression by HSC was confirmed by
      reverse transcription polymerase chain reaction analysis. Surprisingly, HSC also
      expressed mRNA for CCR3 and CCR9, although they failed to migrate to the ligands
      for these receptors. The sharply restricted chemotactic responsiveness of HSC is
      unique among leukocytes and may be necessary for the specific homing of
      circulating HSC to bone marrow, as well as for the maintenance of HSC in
      hematopoietic microenvironments.

PMID- 11994420
TI  - Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella
      from reactive nitrogen intermediates.
AB  - Salmonella typhimurium causes an invasive disease in mice that has similarities
      to human typhoid. A type III protein secretion system encoded by Salmonella
      pathogenicity island 2 (SPI2) is essential for virulence in mice, as well as
      survival and multiplication within macrophages. Reactive nitrogen intermediates
      (RNI) synthesized by inducible nitric oxide synthase (iNOS) are involved in the
      control of intracellular pathogens, including S. typhimurium. We studied the
      effect of Salmonella infection on iNOS activity in macrophages.
      Immunofluorescence microscopy demonstrated efficient colocalization of iNOS with
      bacteria deficient in SPI2 but not wild-type Salmonella, and suggests that the
      SPI2 system interferes with the localization of iNOS and Salmonella. Furthermore,
      localization of nitrotyrosine residues in the proximity was observed for SPI2
      mutant strains but not wild-type Salmonella, indicating that peroxynitrite, a
      potent antimicrobial compound, is excluded from Salmonella-containing vacuoles by
      action of SPI2. Altered colocalization of iNOS with intracellular Salmonella
      required the function of the SPI2-encoded type III secretion system, but not of
      an individual "Salmonella translocated effector." Inhibition of iNOS increased
      intracellular proliferation of SPI2 mutant bacteria and, to a lesser extent, of
      wild-type Salmonella. The defect in systemic infection of a SPI2 mutant strain
      was partially restored in iNOS(-/-) mice. In addition to various strategies to
      detoxify RNI or repair damage due to RNI, avoidance of colocalization with RNI is
      important in adaptation of a pathogen to an intracellular life style.

PMID- 11994421
TI  - Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(-/-) mice.
AB  - FcgammaRIIB is a potent lupus susceptibility gene as demonstrated by the
      observation that mice deficient in this molecule develop spontaneous antinuclear
      antibodies (ANA) and fatal glomerulonephritis when on the C57BL/6 background. To
      determine the mechanisms underlying the epistasis displayed by this gene we have
      constructed hybrids between FcgammaRIIB(-/-) and the systemic lupus erythematosus
      (SLE) modifiers yaa and lpr and the susceptibility locus Sle1. Sle1 and B6.RIIB(
      /-) are both physically and functionally coupled; compound heterozygotes of Sle1
      and B6.RIIB(-/-) develop significant disease, while single heterozygotes display
      no evidence of autoimmunity or disease, indicating that these genes lie on the
      same genetic pathway resulting in the loss of tolerance to nuclear antigens.
      However, the generation of ANA in itself is insufficient to account for the
      severity of autoimmune disease in this model, as demonstrated by analysis of yaa
      and lpr hybrids. Thus, B6.RIIB(-/-)/lpr mice are protected from disease
      progression, despite equivalent titers of ANA. In contrast, B6.RIIB(-/-)/yaa mice
      have significantly enhanced disease despite reduced ANA titers. Yaa modifies the
      specificity and thus the pathogenicity of the B6. RIIB(-/-) ANA, by converting
      them to antinucleolar antibodies. In addition to these known modifier pathways,
      we have discovered two novel, recessive loci contributed by the C57BL/6 genome
      that are required for the ANA phenotype, further indicating the epistatic
      properties of this SLE model.

PMID- 11994422
TI  - Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major
      histocompatibility complex complexes: a buried alloreactive mutation subtly
      alters peptide presentation substantially increasing V(beta) Interactions.
AB  - The crystal structures of the 2C/H-2K(bm3)-dEV8 allogeneic complex at 2.4 A and H
      2K(bm3)-dEV8 at 2.15 A, when compared with their syngeneic counterparts,
      elucidate structural changes that induce an alloresponse. The Asp77Ser mutation
      that imbues H-2K(bm3)-dEV8 with its alloreactive properties is located beneath
      the peptide and does not directly contact the T cell receptor (TCR). However, the
      buried mutation induces local rearrangement of the peptide itself to preserve
      hydrogen bonding interactions between the peptide and the alpha(1) 77 residue.
      The COOH terminus of the peptide main chain is tugged toward the alpha(1)-helix
      such that its presentation to the TCR is altered. These changes increase the
      stability of the allogeneic peptide-major histocompatibility complex (pMHC)
      complex and increase complementarity in the TCR-pMHC interface, placing greater
      emphasis on recognition of the pMHC by the TCR beta-chain, evinced by an increase
      in shape complementarity, buried surface area, and number of TCR-pMHC contacting
      residues. A nearly fourfold increase in the number of beta-chain-pMHC contacts is
      accompanied by a concomitant 64% increase in beta-chain-pMHC shape
      complementarity. Thus, the allogeneic mutation causes the same peptide to be
      presented differently, temporally and spatially, by the allogeneic and syngeneic
      MHCs.

PMID- 11994423
TI  - DNA double-strand breaks: prior to but not sufficient in targeting hypermutation.
AB  - The activation-induced cytidine deaminase (AID) is required for somatic
      hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin (Ig)
      genes, both of which are associated with DNA double-strand breaks (DSBs). As AID
      is capable of deaminating deoxy-cytidine (dC) to deoxy-uracil (dU), it might
      induce nicks (single strand DNA breaks) and also DNA DSBs via a U-DNA glycosylase
      mediated base excision repair pathway ('DNA-substrate model'). Alternatively, AID
      functions like its closest homologue Apobec1 as a catalytic subunit of a RNA
      editing holoenzyme ('RNA-substrate model'). Although rearranged Vlambda genes are
      preferred targets of SHM we found that germinal center (GC) B cells of AID
      proficient and -deficient Vlambda1-expressing GC B cells display a similar
      frequency, distribution, and sequence preference of DSBs in rearranged and also
      in germline Vlambda1 genes. The possible roles of DSBs in relation to AID
      function and SHM are discussed.

PMID- 11994424
TI  - The activation-induced deaminase functions in a postcleavage step of the somatic
      hypermutation process.
AB  - Activation of B cells by antigen fuels two distinct molecular modifications of
      immunoglobulin (Ig) genes. Class-switch recombination (CSR) replaces the Ig(mu)
      heavy chain constant region with a downstream constant region gene, thereby
      altering the effector function of the resulting antibodies. Somatic hypermutation
      (SHM) introduces point mutations into the variable regions of Ig genes, thereby
      changing the affinity of antibody for antigen. Mechanistic overlap between the
      two reactions has been suggested by the finding that both require the activation
      induced cytidine deaminase (AID). It has been proposed that AID initiates both
      CSR and SHM by activating a common nuclease. Here we provide evidence that cells
      lacking AID, or expressing a dominant negative form of the protein, are still
      able to incur DNA lesions in SHM target sequences. The results indicate that an
      intact cytidine deaminase motif is required for AID function, and that AID acts
      downstream of the initial DNA lesions in SHM.

PMID- 11994425
TI  - Sialic acid binding domains of CD22 are required for negative regulation of B
      cell receptor signaling.
AB  - CD22, a negative regulator of B cell antigen receptor signaling, binds
      glycoconjugates terminating in alpha2, 6 sialic acid. The physiological ligand(s)
      for CD22 remain unknown. We asked whether the sialic acid binding domains are
      necessary for CD22 to function as a negative regulator. We generated two mutants
      that lack sialic acid binding activity and expressed them in a novel CD22(-/-)
      murine B cell line. Anti-IgM activated B cells expressing either CD22 mutant had
      greater Ca(2+) responses than cells expressing wild-type CD22. Each variant also
      had reduced CD22 tyrosine phosphorylation and Src homology 2 domain-containing
      protein tyrosine phosphatase-1 association. These data suggest that the alpha2, 6
      sialic acid ligand binding activity of CD22 is critical for its negative
      regulatory functions.

PMID- 11994426
TI  - The ligand-binding domain of CD22 is needed for inhibition of the B cell receptor
      signal, as demonstrated by a novel human CD22-specific inhibitor compound.
AB  - CD22 is a B cell-specific transmembrane protein of the Siglec family. It binds
      specifically to alpha2,6-linked sialic acid (Sia) residues, which are also
      present on glycoproteins on the B cell surface. CD22 acts as a negative regulator
      in B cell receptor-mediated signaling by recruitment of Src homology 2 domain
      containing tyrosine phosphatase (SHP)-1 to its intracellular tail. To analyze how
      ligand-binding of CD22 influences its intracellular signaling domain, we designed
      synthetic sialosides as inhibitors for the lectin domain of CD22. One of these
      compounds inhibited binding of human CD22-Fc to target cells over 200-fold better
      than Sia and was highly selective for human CD22. When Daudi cells or primary B
      cells were stimulated with anti-immunoglobulin (Ig)M in presence of this
      sialoside inhibitor, a higher Ca(2+) response was observed, similar to CD22
      deficient B cells. Accordingly, a lower tyrosine-phosphorylation of CD22 and SHP
      1 recruitment was demonstrated in presence of the sialoside. Thus, by interfering
      with ligand binding of CD22 on the B cell surface, we have shown for the first
      time that the lectin domain of CD22 has a direct, positive influence on its
      intracellular inhibitory domain. Also, we have developed a novel low molecular
      weight compound which can enhance the response of human B cells.

PMID- 11994427
TI  - Very low affinity B cells form germinal centers, become memory B cells, and
      participate in secondary immune responses when higher affinity competition is
      reduced.
AB  - To understand the relationship between the affinity of the B cell antigen
      receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H
      chain transgenic (Tg) mice were created. H50Gmu(a) and T1(V23)mu(a) mice express
      mu H chain transgenes that associate with the lambda1 L chains to bind the (4
      hydroxy-3-nitrophenyl)acetyl hapten with association constants (K(a)s) of only
      1.2 x 10(5) M(-1) and 3 x 10(4) M(-1), respectively. Both lines mounted
      substantial antibody-forming cell (AFC) and germinal center (GC) responses.
      H50Gmu(a) Tg mice also generated memory B cells. T1(V23)mu(a) B cells formed AFC
      and GCs, but were largely replaced in late GCs by antigen-specific cells that
      express endogenous BCRs. Thus, B lymphocytes carrying BCRs with affinities
      previously thought to be irrelevant in specific immune responses are in fact
      capable of complete T cell-dependent immune responses when relieved of
      substantial competition from other B cells. The failure to observe such B cells
      normally in late primary responses and in memory B cell populations is the result
      of competition, rather than an intrinsic inability of low affinity B cells.

PMID- 11994428
TI  - Idiotypes expressed early in experimental Schistosoma mansoni infections predict
      clinical outcomes of chronic disease.
AB  - In murine Schistosoma mansoni infections, schistosome-specific cross-reactive
      idiotypes (CRI) are present in the sera of mice with moderate splenomegaly
      syndrome (MSS) at 20 wk after infection. In contrast, sera from animals that have
      the more severe hypersplenomegaly syndrome (HSS) at 20 wk of infection do not
      express these CRI in their sera. To examine when these regulatory CRI first
      appear in mice that eventually develop MSS, sera from infected animals were
      monitored for CRI from 1.5 to 20 wk of infection. In mice that eventually
      developed MSS, CRI were detected by 5 to 6 wk after infection, plateaued by 8 to
      10 wk, and persisted through 20 wk of infection. Animals that developed HSS
      pathology or that died before 20 wk of infection never expressed CRI. Moreover,
      CRI levels present in the sera of mice at 6 wk of infection were inversely
      correlated with splenomegaly and hepatic fibrosis, but not with parasitologic
      measures, at 20 wk after infection. These results suggest that critical events
      occur very early in some schistosome infections that induce the production of
      regulatory idiotypes and that the presence or absence of these idiotypes
      predicts, and possibly determines, subsequent morbidity.

PMID- 11994429
TI  - The function of AID in somatic mutation and class switch recombination: upstream
      or downstream of DNA breaks.

PMID- 11994430
TI  - Cutting edge: requirement for IL-15 in the generation of primary and memory
      antigen-specific CD8 T cells.
AB  - IL-15 and IL-15Ralpha are required for generation of memory-phenotype CD8 T cells
      in unimmunized mice. However, the role of IL-15 in primary expansion and
      generation of Ag-specific memory CD8 T cells in vivo has not been investigated.
      We characterized the CD8 T cell response against vesicular stomatitis virus (VSV)
      in IL-15(-/-) and IL-15Ralpha(-/-) mice. Surprisingly, IL-15 was required for
      primary expansion of VSV-specific CD8 T cells. The generation of VSV-specific
      memory CD8 T cells was also impaired without IL-15 signaling, and this defect
      correlated with a decrease in memory CD8 T cell turnover. Despite minimal
      proliferation without IL-15, a subset of memory cells survived long-term. IL
      15Ralpha expression was low on naive CD8 T cells, up-regulated on Ag-specific
      effector cells, and sustained on memory cells. Thus, IL-15 was important for the
      generation and the subsequent maintenance of antiviral memory CD8 T cells.

PMID- 11994431
TI  - Cutting edge: selective impairment of CD8+ T cell function in mice lacking the
      TNF superfamily member LIGHT.
AB  - Interactions of LIGHT and its receptors, herpesvirus entry mediator on T cells
      and lymphotoxin beta receptor on stromal cells, are implicated in the regulation
      of lymphoid organogenesis, costimulation of T cells, and activation of dendritic
      cells. In this work we report that LIGHT-deficient mice had normal lymphoid
      organs with T cells and APCs that normally responded to Ag stimulation and
      normally stimulated T cells. Although the number of Vbeta8(+) T cells in naive
      LIGHT(+/+) and LIGHT(-/-) mice was identical, Vbeta8(+)CD8(+) T cell
      proliferation in response to staphylococcal enterotoxin B was significantly lower
      in LIGHT(-/-) mice. Consistently, induction and cytokine secretion of CD8(+) CTL
      to MHC class I-restricted peptide was also reduced in LIGHT(-/-) mice. However,
      the proliferative response of Vbeta8(+)CD4(+) T cells to staphylococcal
      enterotoxin B was comparable in LIGHT(-/-) and LIGHT(+/+) mice. Our results
      suggest that LIGHT is required for activation of normal CD8(+) T cells but not
      CD4(+) T cells.

PMID- 11994432
TI  - Evidence for a dual mechanism for IL-10 suppression of TNF-alpha production that
      does not involve inhibition of p38 mitogen-activated protein kinase or NF-kappa B
      in primary human macrophages.
AB  - IL-10 is a potent anti-inflammatory cytokine and inhibitor of TNF-alpha
      production. The molecular pathways by which IL-10 inhibits TNF-alpha production
      are obscure, with diverse mechanisms having been published. In this study, a new
      approach has been taken for the study of human cells. Adenovirus was used to
      deliver TNF-alpha promoter-based luciferase reporter genes to primary human
      monocytic cells. The reporter genes were highly responsive to macrophage
      activation and appeared to mirror the behavior of the endogenous TNF-alpha gene.
      When added, either with or after the stimulus, IL-10 required the 3' untranslated
      region of the TNF-alpha gene to inhibit luciferase mRNA and protein expression,
      indicating a posttranscriptional mechanism. However, if macrophages were
      incubated with IL-10 before activation, inhibition of gene expression was also
      mediated by the 5' promoter, suggesting a transcriptional mechanism. To our
      knowledge, this is the first time that a dual mechanism for IL-10 function has
      been demonstrated. Studies to elucidate the mechanisms underlying the inhibition
      of TNF-alpha production addressed the effect of IL-10 on the activation of p38
      mitogen-activated protein kinase and NF-kappaB. However, these studies could
      demonstrate no requirement for the inhibition of p38 mitogen-activated protein
      kinase or NF-kappaB activation as potential mechanisms. Overall, these results
      may explain the diversity previously ascribed to the complex mechanisms of IL-10
      anti-inflammatory activity.

PMID- 11994433
TI  - Modulation of dendritic cell differentiation and maturation by decoy receptor 3.
AB  - Decoy receptor 3 (DcR3), a soluble receptor belonging to the TNFR superfamily, is
      a receptor for both Fas ligand (FasL) and LIGHT. It has been demonstrated that
      DcR3 is up-regulated in lung and colon cancers, thus promoting tumor growth by
      neutralizing the cytotoxic effects of FasL and LIGHT. In this study, we found
      that DcR3.Fc profoundly modulated dendritic cell differentiation and maturation
      from CD14(+) monocytes, including the up-regulation of CD86/B7.2, and the down
      regulation of CD40, CD54/ICAM-1, CD80/B7.1, CD1a, and HLA-DR. Moreover, DcR3
      treated dendritic cells suppressed CD4(+) T cell proliferation in an allogeneic
      MLR and up-regulated IL-4 secretion of CD4(+)CD45RA(+) T cells. This suggests
      that DcR3.Fc may act not only as a decoy receptor to FasL and LIGHT, but also as
      an effector molecule to skew T cell response to the Th2 phenotype.

PMID- 11994434
TI  - Immunostimulatory CpG-DNA activates murine microglia.
AB  - Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-DNA)
      triggers innate immune cells through the pattern recognition receptor Toll-like
      receptor 9 (TLR-9). CpG-DNA possesses potent immunostimulatory effects on
      macrophages, dendritic cells, and B lymphocytes. Therefore, CpG-DNA contributes
      to inflammation during the course of bacterial infections. In contrast to other
      TLR-dependent microbial patterns, CpG-DNA is a strong inductor of IL-12. Thus, it
      acts as a Th1-polarizing agent that can be utilized as potent vaccine adjuvant.
      To assess the role of CpG-DNA in immune reactions in the CNS, we analyzed the
      effects of CpG-DNA on microglial cells in vitro and in vivo. Primary microglial
      cells as well as microglial cell lines express TLR-9 mRNA. Consequently, CpG-DNA
      activated microglial cells in vitro and induced TNF-alpha, IL-12p40, IL-12p70,
      and NO. Furthermore, MHC class II, B7-1, B7-2, and CD40 molecules were up
      regulated. In addition, phagocytic activity of microglia was enhanced. After
      intracerebroventricular injection of CpG-DNA, microglial cells were activated and
      produced TNF-alpha and IL-12p40 transcripts, as shown by in situ hybridization.
      These results indicate that microglia is sensitive to CpG-DNA. Thus, bacterial
      DNA containing CpG motifs could not only play an important role during infections
      of the CNS, but also might trigger and sustain Th1-dominated immunopathogenic
      reactions.

PMID- 11994435
TI  - Expression of CD94/NKG2-A on human T lymphocytes is induced by IL-12:
      implications for adoptive immunotherapy.
AB  - NK cell receptors (NKRs) are expressed on a subset of human T cells,
      predominantly CD8(+), within which they can modulate TCR-mediated functions. In
      an attempt to identify the mechanisms leading to NKR expression, we analyzed the
      capacity of IL-12 to modulate the expression by T cells of the components of the
      CD94/NKG2-A inhibitory receptor, a member of the C-type lectin-like family of
      NKR. We show that IL-12 induces the expression of NKG2-A and/or CD94 by CD8(+) T
      cells in culture, and that this induction was mediated neither by IFN-gamma nor
      by IL-15. We also show, using the redirected killing assay, that IL-12-induced
      expression of both CD94 and NKG2-A led to the acquisition by T cells of a
      functional inhibitory receptor. Expression of the CD94/NKG2-A inhibitory receptor
      was also induced by IL-12 during T cell Ag stimulation so that in the presence of
      this cytokine a high proportion of melanoma-reactive CTL induced from PBL by
      melanoma peptide stimulation expressed this receptor. This study emphasizes the
      implication of IL-12 in the modulation of immune responses through NKR induction.

PMID- 11994436
TI  - Human B cells become highly responsive to macrophage-inflammatory protein-3
      alpha/CC chemokine ligand-20 after cellular activation without changes in CCR6
      expression or ligand binding.
AB  - CCR6 is the only known receptor for the chemokine macrophage-inflammatory protein
      (MIP)-3alpha/CC chemokine ligand (CCL)20. We have shown previously that CCR6 is
      expressed on peripheral blood B cells, but CCR6 activity on these cells is low in
      in vitro assays. We report that MIP-3alpha/CCL20-induced calcium flux and
      chemotaxis can be enhanced significantly on peripheral blood and tonsillar B
      cells after activation by cross-linking surface Ag receptors. Of particular
      interest is the fact that the enhanced activity on B cells was not associated
      with an increase in CCR6 expression as assessed by levels of receptor mRNA,
      surface staining, or MIP-3alpha/CCL20 binding sites, or by a change in the
      affinity of the receptor for ligand. These data convincingly demonstrate that
      responses to a chemokine can be regulated solely by changes in the downstream
      pathways for signal transduction resulting from Ag receptor activation, and
      establish CCR6 as an efficacious receptor on human B cells.

PMID- 11994437
TI  - Death ligand TRAIL induces no apoptosis but inhibits activation of human
      (auto)antigen-specific T cells.
AB  - TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily,
      induces apoptosis in susceptible cells, which can be both malignant and
      nontransformed. Despite homologies among the death ligands, there are great
      differences between the TRAIL system on the one hand and the TNF and CD95 systems
      on the other hand. In particular, TRAIL-induced apoptosis differs between rodents
      and man. Studies on animal models of autoimmune diseases suggested an influence
      of TRAIL on T cell growth and effector functions. Because we previously
      demonstrated that TRAIL does not induce apoptosis in human (auto)antigen-specific
      T cells, we now asked whether TRAIL exhibits other immunoregulatory properties in
      these cells. Active TRAIL inhibited calcium influx through store-operated calcium
      release-activated calcium channels, IFN-gamma/IL-4 production, and proliferation.
      These effects were independent of APC, Ag specificity, and Th differentiation,
      and no differences were detected between healthy donors and multiple sclerosis
      patients. TRAIL affected neither the expression of the cell cycling inhibitor
      p27(Kip1) nor the capacity of T cells to produce IL-2 upon Ag rechallenge,
      indicating that signaling via TRAIL receptor does not induce T cell anergy.
      Instead, the TRAIL-induced hypoproliferation could be attributed to the down
      regulation of the cyclin-dependent kinase 4, indicating a G(1) arrest of the cell
      cycle. Thus, although it does not contribute to mechanisms of peripheral T cell
      tolerance such as clonal anergy or deletion by apoptosis, TRAIL can directly
      inhibit activation of human T cells via blockade of calcium influx.

PMID- 11994438
TI  - Human V gamma 2V delta 2 T cells augment migration-inhibitory factor secretion
      and counteract the inhibitory effect of glucocorticoids on IL-1 beta and TNF
      alpha production.
AB  - In immune cells, proinflammatory cytokine gene expression is regulated by
      glucocorticoids, whereas migration-inhibitory factor (MIF), a pleiotropic
      cytokine, has the unique property of counteracting the inhibitory effect of
      glucocorticoids on TNF-alpha and IL-1beta secretion. A few lines of evidence
      suggest that gammadelta T cells play an important role in immunoregulation.
      However, it is unknown whether human gammadelta T cells participate in regulating
      MIF secretion, and how gammadelta T cells, glucocorticoids, and cytokines
      converge to give a unified physiological response. In this study, we demonstrate
      that human Vgamma2Vdelta2 T cells augment MIF secretion. Remarkably, these
      Vgamma2Vdelta2 T cells, functioning similarly to MIF in part, counteracted
      inhibition of dexamethasone on production of IL-1beta and TNF-alpha. SCID mice
      reconstituted with human PBMC that were mock depleted of Vdelta2 T cells and
      repeatedly infected with lethal dose of Escherichia coli had shorter survival
      time than those reconstituted with PBMC that were depleted of Vdelta2 T cells.
      Thus, human Vgamma2Vdelta2 T cells are likely to play broad-spectrum roles in
      immunoregulation and immunopathology by influencing MIF secretion and the
      immunomodulatory function of glucocorticoids.

PMID- 11994439
TI  - 4-1BB ligand-mediated costimulation of human T cells induces CD4 and CD8 T cell
      expansion, cytokine production, and the development of cytolytic effector
      function.
AB  - 4-1BB (CD137) is a costimulatory member of the TNFR family expressed on activated
      T cells. Its ligand, 4-1BBL, is expressed on activated APC. In the mouse, CD8 T
      cells are preferentially activated by agonistic anti-murine 4-1BB Abs. However,
      murine 4-1BBL can stimulate both CD4 and CD8 T cells. To date, there are only
      limited data on the effects of 4-1BBL on human T cell responses. To further
      understand the role of 4-1BBL in human T cell responses, we compared human CD4
      and CD8 T cell responses to transfected human 4-1BBL plus TCR-mediated
      stimulation. Both human CD4 and CD8 T cells responded to 4-1BBL. The presence of
      4-1BBL on the APC led to increased expansion, cytokine production, and the
      development of cytolytic effector function by human T cells. In unfractionated T
      cell cultures, CD4 and CD8 T cells could expand to a similar extent in response
      to signals through the TCR and 4-1BB, as measured by CFSE labeling and by
      quantitating T cell numbers in the cultures. In contrast to the results with
      total T cells, isolated CD8 T cells produced less IL-2 and expanded to a lesser
      extent than isolated CD4 T cells responding to 4-1BBL. Thus, 4-1BBL is most
      effective when both CD4 and CD8 T cells are included in the cultures. CD28 and 4
      1BB were found to synergize in the induction of IL-2 by human T cells, and CTLA
      Ig partially blocked 4-1BBL-dependent IL-2 production. However, a portion of the
      4-1BBL-mediated effects were independent of CD28-B7 interaction.

PMID- 11994440
TI  - IFN-alpha beta promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by
      immunostimulatory DNA-based vaccines.
AB  - Immunostimulatory sequence (ISS) DNA containing unmethylated CpG dinucleotides
      stimulate NK and APC to secrete proinflammatory cytokines, including IFN
      alphabeta and -gamma, TNF-alpha, and IL-6 and -12, and to express costimulatory
      surface molecules such as CD40, B7-1, and B7-2. Although ISS DNA has little
      direct effect on T cells by these criteria, immunization of wild-type mice with
      ISS DNA and OVA results in Ag-specific CTL and Th1-type T helper activity. This
      investigation examines the mechanisms by which ISS DNA primes CD8(+) and CD4(+)
      lymphocyte activities. In this report we demonstrate that ISS DNA regulates the
      expression of costimulatory molecules and TAP via a novel autocrine or paracrine
      IFN-alphabeta pathway. Coordinated regulation of B7 costimulation and TAP
      dependent cross-presentation results in priming of Ag-specific CD8(+) CTL,
      whereas CD40, B7, and IL-12 costimulation is required for priming of CD4(+) Th
      cells by ISS-based vaccines.

PMID- 11994441
TI  - Protective antitumor immunity induced by a costimulatory thalidomide analog in
      conjunction with whole tumor cell vaccination is mediated by increased Th1-type
      immunity.
AB  - Thalidomide and its novel T cell costimulatory analogs (immunomodulatory drugs)
      are currently being assessed in the treatment of patients with advanced cancer.
      However, neither tumor-specific T cell costimulation nor effective antitumor
      activity has been demonstrated in vivo. In this study, we assessed the ability of
      an immunomodulatory drug (CC-4047/ACTIMID) to prime a tumor-specific immune
      response following tumor cell vaccination. We found that the presence of CC-4047
      during the priming phase strongly enhanced antitumor immunity in the vaccinated
      group, and this correlated with protection from subsequent live tumor challenge.
      Protection was associated with tumor-specific production of IFN-gamma and was
      still observed following a second challenge with live tumor cells 60 days later.
      Furthermore, CD8(+) and CD4(+) splenocyte fractions from treated groups secreted
      increased IFN-gamma and IL-2 in response to tumor cells in vitro. Coculture of
      naive splenocytes with anti-CD3 mAb in the presence of CC-4047 directly
      costimulated T cells and increased Th1-type cytokines. Our results are the first
      to demonstrate that a costimulatory thalidomide analog can prime protective, long
      lasting, tumor-specific, Th1-type responses in vivo and further support their
      ongoing clinical development as novel anti-cancer agents.

PMID- 11994442
TI  - Patterns of chemokine receptor expression on peripheral blood gamma delta T
      lymphocytes: strong expression of CCR5 is a selective feature of V delta 2/V
      gamma 9 gamma delta T cells.
AB  - Gammadelta T lymphocytes play an important role in the immune defense against
      infection, based on the unique reactivity of human Vdelta2Vgamma9 gammadelta T
      cells toward bacterial phosphoantigens. Chemokines and their corresponding
      receptors orchestrate numerous cellular reactions, including leukocyte migration,
      activation, and degranulation. In this study we investigated the expression of
      various receptors for inflammatory and homeostatic chemokines on peripheral blood
      gammadelta T cells and compared their expression patterns with those on alphabeta
      T cells. Although several of the analyzed receptors (including CCR6, CCR7, CXCR4,
      and CXCR5) were not differentially expressed on gammadelta vs alphabeta T cells,
      gammadelta T cells expressed strongly increased levels of the RANTES/macrophage
      inflammatory protein-1alpha/-1beta receptor CCR5 and also enhanced levels of CCR1
      3 and CXCR1-3. CCR5 expression was restricted to Vdelta2 gammadelta T cells,
      while the minor subset of Vdelta1 gammadelta T cells preferentially expressed
      CXCR1. Stimulation with heat-killed extracts of Mycobacterium tuberculosis down
      modulated cell surface expression of CCR5 on gammadelta T cells in a macrophage
      dependent manner, while synthetic phosphoantigen isopentenyl pyrophosphate and
      CCR5 ligands directly triggered CCR5 down-modulation on gammadelta T cells. The
      functionality of chemokine receptors CCR5 and CXCR3 on gammadelta T cells was
      demonstrated by Ca(2+) mobilization and chemotactic response to the respective
      chemokines. Our results identify high level expression of CCR5 as a
      characteristic and selective feature of circulating Vdelta2 gammadelta T cells,
      which is in line with their suspected function as Th1 effector T cells.

PMID- 11994443
TI  - Absence of Fer protein-tyrosine kinase exacerbates leukocyte recruitment in
      response to endotoxin.
AB  - The group IV cytoplasmic protein-tyrosine kinase Fer has been linked to cellular
      signaling responses to many different stimuli, including growth factors and
      cytokines. However, the biological relevance of Fer activation in vivo has not
      been demonstrated to date. Recently, we generated a transgenic mouse line in
      which Fer protein is expressed but lacks catalytic activity. Homozygous mutant
      mice were viable and fertile, and showed no overt defects. In this study, we used
      intravital microscopy to examine the role of Fer kinase in leukocyte recruitment
      (rolling adhesion and emigration) in response to LPS challenge in skeletal muscle
      microcirculation. In addition, we measured vascular permeability changes (FITC
      albumin leakage, venular-to-interstitial space) in response to Ag to examine
      general endothelial cell function. Local administration of LPS induced decreased
      leukocyte rolling velocity and increased leukocyte adhesion and emigration in
      wild-type mice. LPS-induced changes in leukocyte rolling velocity and rolling
      flux were not significantly different in Fer mutants. However, LPS-induced
      leukocyte adhesion (23 +/- 3 vs 11 +/- 3 cells/100 microm) and emigration (100 +/
      5 vs 28 +/- 7 cells/field) were significantly elevated in Fer-mutant mice
      relative to wild-type mice, respectively, suggesting an essential role for the
      Fer kinase in regulating inflammation-induced leukocyte emigration. Vascular
      permeability increases in response to Ag were similar between the two groups,
      indicating that the ability of endothelial cells to retract is intact in the
      absence of Fer kinase. These data provide the first evidence for a biological
      role for Fer in regulation of leukocyte recruitment during the innate immune
      response.

PMID- 11994444
TI  - Sustained NFAT signaling promotes a Th1-like pattern of gene expression in
      primary murine CD4+ T cells.
AB  - T cell activation is known to be critically regulated by the extent and duration
      of TCR-induced signaling pathways. The NFAT family of transcription factors is
      believed to play an important role in coupling these quantitative differences in
      TCR-induced signaling events into changes in gene expression. In this study we
      have specifically investigated the effects of sustained NFAT signaling on T cell
      activation by introducing a constitutively active mutant version of NFATc1
      (caNFATc1) into primary murine CD4(+) T cells and examining its effects on gene
      expression. We now report that ectopic expression of caNFATc1 partially mimics
      TCR signaling, resulting in enhanced expression of CD25 and CD40 ligand and down
      regulation of CD62L. More importantly, we find that expression of caNFATc1 in T
      cells maintained under either nonpolarizing or Th1-skewing conditions leads to a
      marked selective increase in the number of cells expressing the prototypical Th1
      cytokine, IFN-gamma. Furthermore, when expressed in Th2-skewed cells, caNFATc1
      appears to attenuate Th2 differentiation by decreasing production of IL-4 and
      promoting the expression of IFN-gamma. Finally, we find that caNFATc1 enhances
      expression of functional P-selectin glycoprotein ligand-1, up-regulates Fas
      ligand expression, and increases susceptibility to activation-induced cell death,
      cellular traits that are preferentially associated with Th1 effector cells. Taken
      together, these results suggest that sustained NFAT signaling, mediated by
      ectopic expression of caNFATc1, acts to promote a Th1-like pattern of gene
      expression and thereby serves to highlight the important relationship between the
      degree of NFAT signaling and the qualitative pattern of gene expression induced
      during T cell activation.

PMID- 11994445
TI  - A role for CD147 in thymic development.
AB  - We have previously identified a mAb that binds to a molecule expressed
      preferentially on the surface of cycling thymocytes. In this study the molecule
      recognized by this mAb has been identified in the mouse as CD147 (basigin) by
      expression cloning. We show that CD147 expression correlates with cycling of
      immature thymocytes even in the absence of TCRbeta selection and that ligation of
      this molecule on immature fetal thymocytes inhibits their further development
      into mature T cells.

PMID- 11994446
TI  - Priming Th1 immunity to viral core particles is facilitated by trace amounts of
      RNA bound to its arginine-rich domain.
AB  - Particulate hepatitis B core Ag (C protein) (HBcAg) and soluble hepatitis B
      precore Ag (E protein) (HBeAg) of the hepatitis B virus share >70% of their amino
      acid sequence and most T and B cell-defined epitopes. When injected at low doses
      into mice, HBcAg particles prime Th1 immunity while HBeAg protein primes Th2
      immunity. HBcAg contains 5-20 ng RNA/microg protein while nucleotide binding to
      HBeAg is not detectable. Deletion of the C-terminal arginine-rich domain of HBcAg
      generates HBcAg-144 or HBcAg-149 particles (in which >98% of RNA binding is lost)
      that prime Th2-biased immunity. HBcAg particles, but not truncated HBcAg-144 or 
      149 particles stimulate IL-12 p70 release by dendritic cells and IFN-gamma
      release by nonimmune spleen cells. The injection of HBeAg protein or HBcAg-149
      particles into mice primes Th1 immunity only when high doses of RNA (i.e., 20-100
      microg/mouse) are codelivered with the Ag. Particle-incorporated RNA has thus a
      1000-fold higher potency as a Th1-inducing adjuvant than free RNA mixed to a
      protein Ag. Disrupting the particulate structure of HBcAg releases RNA and
      abolishes its Th1 immunity inducing potency. Using DNA vaccines delivered
      intradermally with the gene gun, inoculation of 1 microg HBcAg-encoding pCI/C
      plasmid DNA primes Th1 immunity while inoculation of 1 microg HBeAg-encoding
      pCI/E plasmid DNA or HBcAg-149-encoding pCI/C-149 plasmid DNA primes Th2
      immunity. Expression data show eukaryotic RNA associated with HBcAg, but not
      HBeAg, expressed by the DNA vaccine. Hence, codelivery of an efficient, intrinsic
      adjuvant (i.e., nanogram amounts of prokaryotic or eukaryotic RNA bound to
      arginine-rich sequences) by HBcAg nucleocapsids facilitates priming of anti-viral
      Th1 immunity.

PMID- 11994447
TI  - Fas-dependent elimination of nonselected CD8 cells and lpr disease.
AB  - MHC/self peptide interactions with cognate coreceptor/TCR complexes are central
      to homeostasis of the T cell repertoire. Recent reports have also underlined the
      critical role of IL-15/IL-2 cytokines in regulating this homeostatic process. In
      this study, we investigate mechanisms that regulate potentially autoreactive CD8
      cells that have escaped intrathymic selection. These cells, upon exit from the
      thymus, express high levels of CD44, B220, and the IL-15R/IL-2R, and undergo fas
      dependent apoptosis. Defects in fas signaling allow increased IL-15/IL-2
      dependent survival of these CD44/B220(+) CD8(+) as well as the double-negative T
      cells characteristic of lpr disease.

PMID- 11994448
TI  - Reevaluation of T cell receptor excision circles as a measure of human recent
      thymic emigrants.
AB  - The human thymus exports newly generated T cells to the periphery. As no markers
      have been identified for these recent thymic emigrants (RTE), it is presently
      impossible to measure human thymic output. T cell receptor excision circles
      (TREC) have been recently used to assess thymic output during both health and
      disease. Using a mathematical model, we quantify age-dependent changes both in
      the number of RTE generated per day and in TREC concentration during an 80-year
      lifespan. Through analyses, we demonstrate that RTE and peripheral T cell
      division have the same potential to affect TREC concentration at any age in
      healthy people. T cell death also influences TREC concentration, but to a lesser
      extent. During aging, our results indicate that thymic involution primarily
      induces an age-dependent decline in TREC concentrations within both CD4(+) and
      CD8(+) T cell populations. We further apply this model for studying TREC
      concentration during HIV-1 infection. Our analyses reveal that a decrease in
      thymic output is the major contributor to the decline in TREC concentration
      within CD4(+) T cells, whereas both increased peripheral T cell division and
      decreased thymic output induce the decline in TREC concentration within CD8(+) T
      cells. Therefore, we suggest that T cell turnover should be examined together
      with TREC concentration as a measure of RTE. If peripheral T cell division
      remains relatively unchanged, then TREC concentration indeed reflects thymic
      output.

PMID- 11994449
TI  - Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK
      cells derived from embryonic stem cells in vitro.
AB  - In mice there are two families of MHC class I-specific receptors, namely the Ly49
      and CD94/NKG2 receptors. The latter receptors recognize the nonclassical MHC
      class I Qa-1(b) and are thought to be responsible for the recognition of missing
      self and the maintenance of self-tolerance of fetal and neonatal NK cells that do
      not express Ly49. Currently, how NK cells acquire individual CD94/NKG2 receptors
      during their development is not known. In this study, we have established a
      multistep culture method to induce differentiation of embryonic stem (ES) cells
      into the NK cell lineage and examined the acquisition of CD94/NKG2 by NK cells as
      they differentiate from ES cells in vitro. ES-derived NK (ES-NK) cells express NK
      cell-associated proteins and they kill certain tumor cell lines as well as MHC
      class I-deficient lymphoblasts. They express CD94/NKG2 heterodimers, but not Ly49
      molecules, and their cytotoxicity is inhibited by Qa-1(b) on target cells. Using
      RT-PCR analysis, we also report that the acquisition of these individual receptor
      gene expressions during different stages of differentiation from ES cells to NK
      cells follows a predetermined order, with their order of acquisition being first
      CD94; subsequently NKG2D, NKG2A, and NKG2E; and finally, NKG2C. Single-cell RT
      PCR showed coexpression of CD94 and NKG2 genes in most ES-NK cells, and flow
      cytometric analysis also detected CD94/NKG2 on most ES-NK cells, suggesting that
      the acquisition of these receptors by ES-NK cells in vitro is nonstochastic,
      orderly, and cumulative.

PMID- 11994450
TI  - Postgestational lymphotoxin/lymphotoxin beta receptor interactions are essential
      for the presence of intestinal B lymphocytes.
AB  - Lymphotoxin (LT), a cytokine belonging to the TNF family, has established roles
      in the formation of secondary lymphoid structures and in the compartmentalization
      of T and B lymphocyte areas of the spleen. In this study, we examine the role of
      LT in directing the composition of intestinal lymphocytes. We report that mice
      deficient in LT have a normal composition of intestinal lamina propria (LP) T
      lymphocytes, and an absence of intestinal LP B lymphocytes. We further refine
      this observation to demonstrate that the interaction of LT with the LTbetaR is
      essential for the presence LP B lymphocytes. The LT/LTbetaR-dependent events
      relevant for the presence of LP B lymphocytes occur after birth, do not require
      the presence of Peyer's patches, lymph nodes, or the spleen; and therefore, are
      distinct and independent from the previously identified roles of LT/LTbetaR. The
      LT-dependent signal relevant for the presence of LP B lymphocytes is optimally
      supplied by a LT-sufficient B lymphocyte, and requires a LTbetaR-sufficient radio
      resistant, non-bone marrow-derived cell. Based upon the severity of the deficit
      of LP B lymphocytes we observed, these novel LT/LTbetaR-dependent events are of
      primary importance in directing the entry and residence of LP B lymphocytes.

PMID- 11994451
TI  - Optimizing the efficacy of epitope-directed DNA vaccination.
AB  - An increasing number of clinical trials has been initiated to test the potential
      of prophylactic or curative vaccination with tumor Ag-encoding DNA vaccines.
      However, in the past years it has become apparent that for many Ags and in
      particular for tumor Ags the intracellular processing and presentation are
      suboptimal. To improve epitope-directed DNA vaccines we have developed a murine
      model system in which epitope-specific, DNA vaccine-induced T cell immunity can
      be followed by MHC tetramer technology directly ex vivo. We have used this well
      defined model to dissect the parameters that are crucial for the induction of
      strong cytotoxic T cell immunity using two independent model Ags. These
      experiments have led to a set of five guidelines for the design of epitope
      directed DNA vaccines, indicating that carboxyl-terminal fusion of the epitope to
      a carrier protein of foreign origin is the most favorable strategy. DNA vaccines
      that are based on these guidelines induce high-magnitude CD8(+) T cell responses
      in >95% of vaccinated animals. Moreover, T cell immunity induced by this type of
      optimized DNA vaccine provides long-term protection against otherwise lethal
      tumor challenges.

PMID- 11994452
TI  - Rat peripheral CD4+CD8+ T lymphocytes are partially immunocompetent thymus
      derived cells that undergo post-thymic maturation to become functionally mature
      CD4+ T lymphocytes.
AB  - CD4+CD8+ double-positive (DP) T cells represent a minor subpopulation of T
      lymphocytes found in the periphery of adult rats. In this study, we show that
      peripheral DP T cells appear among the first T cells that colonize the peripheral
      lymphoid organs during fetal life, and represent approximately 40% of peripheral
      T cells during the perinatal period. Later their proportion decreases to reach
      the low values seen in adulthood. Most DP T cells are small size lymphocytes that
      do not exhibit an activated phenotype, and their proliferative rate is similar to
      that of the other peripheral T cell subpopulations. Only 30-40% of DP T cells
      expresses CD8beta chain, the remaining cells expressing CD8alphaalpha homodimers.
      However, both DP T cell subsets have an intrathymic origin since they appear in
      the recent thymic emigrant population after injection of FITC intrathymically.
      Functionally, although DP T cells are resistant to undergo apoptosis in response
      to glucocorticoids, they show poor proliferative responses upon CD3/TCR
      stimulation due to their inability to produce IL-2. A fraction of DP T cells are
      not actively synthesizing the CD8 coreceptor, and they gradually differentiate to
      the CD4 cell lineage in reaggregation cultures. Transfer of DP T lymphocytes into
      thymectomized SCID mice demonstrates that these cells undergo post-thymic
      maturation in the peripheral lymphoid organs and that their CD4 cell progeny is
      fully immunocompetent, as judged by its ability to survive and expand in
      peripheral lymphoid organs, to proliferate in response to CD3 ligation, and to
      produce IL-2 upon stimulation.

PMID- 11994453
TI  - Aging-dependent exclusion of antigen-inexperienced cells from the peripheral B
      cell repertoire.
AB  - Aging is accompanied by greatly reduced B cell production in the bone marrow, yet
      peripheral B cell numbers do not decline. We hypothesize that this may reflect
      filling of the peripheral pool with B cells that are long-lived as a consequence
      of specificity for, and chronic stimulation by, environmental Ags. To begin to
      explore this possibility, we analyzed the effects of aging on B cell population
      dynamics in the anti-H2(k/b) 3-83 mu-delta Ig-transgenic mouse. We predicted
      that, because they presumably do not bind environmental Ags, B cells bearing the
      transgenic receptor may be lost in aged animals. As seen in nontransgenic
      animals, total splenic B cell numbers remained constant with age in the Ig
      transgenic animals despite reduced B cell production. Importantly, although the
      few newly produced B cells in the bone marrow of aged mice are 3-83 positive, the
      peripheral compartment of these mice is dominated by B cells that express
      endogenous Ig genes rather than the transgenes. This population includes large
      numbers of marginal zone-like and CD21(low/-)CD23(low/-)IgM(low) B cells, as well
      as elevated numbers of CD5+ B cells. Many of these cells express only non-B220
      CD45 isoforms, suggesting that they may be memory cells. A significant proportion
      of aged transgenic animals produce autoantibodies that are reactive with ssDNA,
      dsDNA, or histones. Results support the hypothesis that, in the face of severely
      reduced production with age, B cells are selected based on reactivity to
      environmental Ags, accumulate, and display activated phenotypes. Cells bearing 3
      83-transgenic receptors are excluded from this population due to their
      specificity. Beyond their importance in aging, these findings define a novel form
      of receptor revision in which B cells are selected rather than deleted based on
      Ag reactivity.

PMID- 11994454
TI  - The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim
      in response to IL-2.
AB  - The cytokine IL-2 plays a very important role in the proliferation and survival
      of activated T cells. These effects of IL-2 are dependent on signaling through
      the phosphatidylinositol 3-kinase (PI3K) pathway. We and others have shown that
      PI3K, through activation of protein kinase B/Akt, inhibits transcriptional
      activation by a number of forkhead transcription factors (FoxO1, FoxO3, and
      FoxO4). In this study we have investigated the role of these forkhead
      transcription factors in the IL-2-induced T cell proliferation and survival. We
      show that IL-2 regulates phosphorylation of FoxO3 in a PI3K-dependent fashion.
      Phosphorylation and inactivation of FoxO3 appears to play an important role in IL
      2-mediated T cell survival, because mere activation of FoxO3 is sufficient to
      trigger apoptosis in T cells. Indeed, active FoxO3 can induce expression of IL-2
      regulated genes, such as the cdk inhibitor p27(Kip1) and the proapoptotic Bcl-2
      family member Bim. Furthermore, we show that IL-2 triggers a rapid, PI3K
      dependent, phosphorylation of FoxO1a in primary T cells. Thus, we propose that
      inactivation of FoxO transcription factors by IL-2 plays a critical role in T
      cell proliferation and survival.

PMID- 11994455
TI  - Increased generation of dendritic cells from myeloid progenitors in autoimmune
      prone nonobese diabetic mice.
AB  - Aberrant dendritic cell (DC) development and function may contribute to
      autoimmune disease susceptibility. To address this hypothesis at the level of
      myeloid lineage-derived DC we compared the development of DC from bone marrow
      progenitors in vitro and DC populations in vivo in autoimmune diabetes-prone
      nonobese diabetic (NOD) mice, recombinant congenic nonobese diabetes-resistant
      (NOR) mice, and unrelated BALB/c and C57BL/6 (BL/6) mice. In GM-CSF/IL-4
      supplemented bone marrow cultures, DC developed in significantly greater numbers
      from NOD than from NOR, BALB/c, and BL/6 mice. Likewise, DC developed in greater
      numbers from sorted (lineage(-)IL-7Ralpha(-)SCA-1(-)c-kit(+)) NOD myeloid
      progenitors in either GM-CSF/IL-4 or GM-CSF/stem cell factor (SCF)/TNF-alpha.
      [(3)H]TdR incorporation indicated that the increased generation of NOD DC was due
      to higher levels of myeloid progenitor proliferation. Generation of DC with the
      early-acting hematopoietic growth factor, flt3 ligand, revealed that while the
      increased DC-generative capacity of myeloid-committed progenitors was restricted
      to NOD cells, early lineage-uncommitted progenitors from both NOD and NOR had
      increased DC-generative capacity relative to BALB/c and BL/6. Consistent with
      these findings, NOD and NOR mice had increased numbers of DC in blood and thymus
      and NOD had an increased proportion of the putative myeloid DC (CD11c(+)CD11b(+))
      subset within spleen. These findings demonstrate that diabetes-prone NOD mice
      exhibit a myeloid lineage-specific increase in DC generative capacity relative to
      diabetes-resistant recombinant congenic NOR mice. We propose that an imbalance
      favoring development of DC from myeloid-committed progenitors predisposes to
      autoimmune disease in NOD mice.

PMID- 11994456
TI  - Conversion of naive T cells to a memory-like phenotype in lymphopenic hosts is
      not related to a homeostatic mechanism that fills the peripheral naive T cell
      pool.
AB  - To examine directly whether a limited number of naive T cells transferred to
      lymphopenic hosts can truly fill the peripheral naive T cell pool, we compared
      the expansion and phenotype of naive T cells transferred to three different
      hosts, namely recombination-activating gene-deficient mice, CD3epsilon-deficient
      mice, and irradiated normal mice. In all three recipients, the absolute number of
      recovered cells was much smaller than in normal mice. In addition, transferred
      naive T cells acquired a memory-like phenotype that remained stable with time.
      Finally, injected cells were rapidly replaced by host thymic migrants in
      irradiated normal mice. Only continuous output of naive T cells by the thymus can
      generate a full compartment of truly naive T cells. Thus, conversion of naive T
      cells to a memory-like phenotype in lymphopenic hosts is not related to a
      homeostatic mechanism that fills the peripheral naive T cell pool.

PMID- 11994457
TI  - SHP-1- and phosphotyrosine-independent inhibitory signaling by a killer cell Ig
      like receptor cytoplasmic domain in human NK cells.
AB  - Killer cell Ig-like receptors (KIR) are MHC class I-binding immunoreceptors that
      can suppress activation of human NK cells through recruitment of the Src homology
      2-containing protein tyrosine phosphatase-1 (SHP-1) to two immunoreceptor
      tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains. KIR2DL4
      (2DL4; CD158d) is a structurally distinct member of the KIR family, which is
      expressed on most, if not all, human NK cells. 2DL4 contains only one ITIM in its
      cytoplasmic domain and an arginine in its transmembrane region, suggesting both
      inhibitory and activating functions. While 2DL4 can activate IFN-gamma
      production, dependent upon the transmembrane arginine, the function of the single
      ITIM of 2DL4 remains unknown. In this study, tandem ITIMs of KIR3DL1 (3DL1) and
      the single ITIM of 2DL4 were directly compared in functional and biochemical
      assays. Using a retroviral transduction method, we show in human NK cell lines
      that 1) the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity
      responses; 2) the phosphorylated single ITIM recruits SHP-2 protein tyrosine
      phosphatase, but not SHP-1 in NK cells; 3) expression of dominant-negative SHP-1
      does not block the ability of 2DL4 to inhibit natural cytotoxicity; 4)
      surprisingly, mutation of the tyrosine within the single ITIM does not completely
      abolish inhibitory function; and 5) this correlates with weak SHP-2 binding to
      the mutant ITIM of 2DL4 in NK cells and a corresponding nonphosphorylated ITIM
      peptide in vitro. These results reveal new aspects of the KIR-inhibitory pathway
      in human NK cells, which are SHP-1 and phosphotyrosine independent.

PMID- 11994458
TI  - Role for thymic and splenic regulatory CD4+ T cells induced by donor dendritic
      cells in allograft tolerance by LF15-0195 treatment.
AB  - A 20-day treatment with LF15-0195, a deoxyspergualine analogue, induced allograft
      tolerance in a fully MHC-mismatched heart allograft model in the rat. Long-term
      allografts displayed minimal cell infiltration with no signs of chronic
      rejection. CD4+ spleen T cells from tolerant LF15-0195-treated recipients were
      able to suppress in vitro proliferation of allogeneic CD4+ T cells and to
      transfer tolerance to second syngeneic recipients, demonstrating dominant
      suppression by regulatory cells. A significant increase in the percentage of
      CD4+CD25+ T cells was observed in the thymus and spleen from tolerant LF15-0195
      treated recipient. In vitro direct stimulation with donor APCs demonstrated that
      CD4+ regulatory T cells proliferated weakly and expressed low levels of IFN
      gamma, IL-10, and IL-2. CD4+CD25+ cell depletion increased IL-2 production by
      CD4+CD25- thymic cells, but not splenic cells. Moreover, tolerance was
      transferable with splenic and thymic CD4+CD25+ cells, but also in 50% of cases
      with splenic CD4+CD25- cells, demonstrating that CD25 can be a marker for
      regulatory cells in the thymus, but not in the periphery. In addition, we
      presented evidences that donor APCs were required to induce tolerance and to
      expand regulatory CD4+ T cells. This study demonstrates that LF15-0195 treatment
      induces donor APCs to expand powerful regulatory CD4+CD25+/- T cells present in
      both the central and peripheral compartments.

PMID- 11994459
TI  - Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine
      phosphatase 2A.
AB  - The catalytic subunit of the serine/threonine phosphatase 2A (PP2A) can interact
      with the cytoplasmic tail of CTLA-4. However, the molecular basis and the
      biological significance of this interaction are unknown. In this study, we report
      that the regulatory subunit of PP2A (PP2AA) also interacts with the cytoplasmic
      tail of CTLA-4. Interestingly, TCR ligation induces tyrosine phosphorylation of
      PP2AA and its dissociation from CTLA-4 when coligated. The association between
      PP2AA and CTLA-4 involves a conserved three-lysine motif in the juxtamembrane
      portion of the cytoplasmic tail of CTLA-4. Mutations of these lysine residues
      prevent the binding of PP2AA and enhance the inhibition of IL-2 gene
      transcription by CTLA-4, indicating that PP2A represses CTLA-4 function. Our data
      imply that the lysine-rich motif in CTLA-4 may be used to identify small
      molecules that block its binding to PP2A and act as agonists for CTLA-4 function.

PMID- 11994460
TI  - Visualization of lymphotoxin-beta and lymphotoxin-beta receptor expression in
      mouse embryos.
AB  - The heteromeric lymphotoxin alphabeta ligand (LT) binds to the LTbeta receptor
      (LTbetaR) and provides an essential trigger for lymph node (LN) development.
      LTbetaR signaling is also critical for the emergence of pathological ectopic
      lymph node-like structures and the maintenance of an organized splenic white
      pulp. To better understand the role of LT in development, the expression patterns
      of LTbeta and LTbetaR mRNA were examined by in situ hybridization in the
      developing mouse embryo. Images of LTbeta ligand expression in developing
      peripheral LN in the E18.5 embryo revealed a relatively early phase structure and
      allowed for comparative staging with LN development in rat and humans. The
      LTbetaR is expressed from E16.5 onward in respiratory, salivary, bronchial, and
      gastric epithelium, which may be consistent with early communication events
      between lymphoid elements and epithelial specialization over emerging mucosal LN.
      Direct comparison of mouse fetal and adult tissues by FACS analysis confirmed the
      elevated expression of LTBR in some embryonic epithelial layers. Therefore,
      surface LTBR expression may be elevated during fetal development in some
      epithelial layers.

PMID- 11994461
TI  - Different qualitative and quantitative regulation of V beta TCR transcripts
      during early acute allograft rejection and tolerance induction.
AB  - Recently, using a global method of T cell repertoire analysis, we showed that
      purified naive T cells confronted in vitro with allogeneic APCs in a direct
      pathway-restricted MLR up-regulate their Vbeta mRNAs without exhibiting skewing
      of complementarity-determining region 3 (CDR3) length distribution. In this
      report, using this approach, we show in vivo that Vbeta transcript regulation and
      CDR3 length distribution follow the same pattern during acute rejection of MHC
      incompatible heart allografts. In contrast, in tolerance induction by priming of
      recipients with donor cells, the vigorous Vbeta mRNA accumulation with Gaussian
      CDR3 length distribution is abolished, providing a possible explanation for the
      down-regulation of activated T cells in tolerant animals. In addition, tolerated
      grafts harbor T cells with a highly altered repertoire, suggestive of self
      restricted presentation with some patterns corresponding to previously identified
      regulatory cells.

PMID- 11994462
TI  - CXCR5-transduced bone marrow-derived dendritic cells traffic to B cell zones of
      lymph nodes and modify antigen-specific immune responses.
AB  - Skin-derived migratory dendritic cells (DC), in contrast to bone marrow-derived
      DC (BMDC), express CXCR5, respond to the chemokine CXC ligand 13 (CXCL13) in
      vitro, and are capable of migrating to B cell zones (BCZ) in lymph nodes (LN) in
      vivo. Herein, we analyzed the surface phenotype of skin-derived migratory DC and
      found that 15-35% of MHC class II(high) cells showed high levels of expression of
      CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal
      type DC in mice. To study the effects of CXCR5 on the trafficking dynamics of DC,
      we stably expressed CXCR5 in BMDC by retroviral gene transduction. CXCR5 was
      detected by flow cytometry on transduced cells, which responded to CXCL13 in
      vitro in chemotaxis assays (3-fold over nontransduced BMDC, p < 0.01). When
      injected into the footpads of mice, approximately 40% of injected CXCR5-BMDC were
      observed in BCZ of draining LN. Mice were vaccinated with CXCR5- and vector-BMDC
      that were pulsed with keyhole limpet hemocyanin (KLH) to induce Ag-specific
      cellular and humoral immune responses. Mice injected with CXCR5-BMDC (vs vector
      BMDC) demonstrated marginally less footpad swelling in response to intradermal
      injection of KLH. Interestingly, significantly higher levels of KLH-specific IgG
      (p < 0.05) and IgM (p < 0.01) were found in the serum of mice injected with CXCR5
      BMDC compared with mice immunized with vector-transduced BMDC. Thus, CXCR5 is
      predominantly expressed by dermal-type DC. Moreover, CXCR5 directs BMDC to BCZ of
      LN in vivo and modifies Ag-specific immune responses induced by BMDC vaccination.

PMID- 11994463
TI  - IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor
      associated factor 6/c-Src complex.
AB  - Targeted disruption of either c-Src or TNFR-associated factor 6 (TRAF6) in mice
      causes osteoclast dysfunction and an osteopetrotic phenotype, suggesting that
      both molecules play important roles in osteoclastic bone resorption. We
      previously demonstrated that IL-1 induces actin ring formation and osteoclast
      activation. In this study, we examined the relationship between IL-1/TRAF6
      dependent and c-Src-mediated pathways in the activation of osteoclast-like cells
      (prefusion cells (pOCs); multinucleated cells) formed in the murine coculture
      system. In normal pOCs, IL-1 induces actin ring formation and tyrosine
      phosphorylation of p130(Cas), a known substrate of c-Src. However, in Src
      deficient pOCs, p130(Cas) was not tyrosine phosphorylated following IL-1
      treatment. In normal pOCs treated with IL-1, anti-TRAF6 Abs coprecipitate
      p130(Cas), protein tyrosine kinase 2, and c-Src. In Src-deficient pOCs, this
      molecular complex was not detected, suggesting that c-Src is required for
      formation of the TRAF6, p130(Cas), and protein tyrosine kinase 2 complex.
      Moreover, an immunocytochemical analysis revealed that in osteoclast-like
      multinucleated cells, IL-1 induced redistribution of TRAF6 to actin ring
      structures formed at the cell periphery, where TRAF6 also colocalized with c-Src.
      Taken together, these data suggest that IL-1 signals feed into the tyrosine
      kinase pathways through a TRAF6-Src molecular complex, which regulates the
      cytoskeletal reorganization essential for osteoclast activation.

PMID- 11994464
TI  - Adapter molecule Grb2-associated binder 1 is specifically expressed in marginal
      zone B cells and negatively regulates thymus-independent antigen-2 responses.
AB  - Grb2-associated binder 1 (Gab1) is a member of the Gab/daughter of sevenless
      family of adapter molecules involved in the signal transduction pathways of a
      variety of growth factors, cytokines, and Ag receptors. To know the role for Gab1
      in hematopoiesis and immune responses in vivo, we analyzed radiation chimeras
      reconstituted with fetal liver (FL) cells of Gab1(-/-) mice, because Gab1(-/-)
      mice are lethal to embryos. Transfer of Gab1(-/-) FL cells of 14.5 days post
      coitum rescued lethally irradiated mice, indicating that Gab1 is not essential
      for hematopoiesis. Although mature T and B cell subsets developed normally in the
      peripheral lymphoid organs, reduction of pre-B cells and increase of myeloid
      cells in the Gab1(-/-) FL chimeras suggested the regulatory roles for Gab1 in
      hematopoiesis. The chimera showed augmented IgM and IgG1 production to thymus
      independent (TI)-2 Ag, although they showed normal responses for thymus-dependent
      and TI-1 Ags, indicating its negative role specific to TI-2 response. Gab1(-/-)
      splenic B cells stimulated with anti-delta-dextran plus IL-4 plus IL-5 showed
      augmented IgM and IgG1 production in vitro that was corrected by the retrovirus
      mediated transfection of the wild-type Gab1 gene, clearly demonstrating the cell
      autonomous, negative role of Gab1. Furthermore, we showed that the negative role
      of Gab1 required its Src homology 2-containing tyrosine phosphatase-2 binding
      sites. Cell fractionation analysis revealed that nonfollicular B cells were
      responsible for the augmented Ab production in vitro. Consistent with these
      results, the Gab1 gene was expressed in marginal zone B cells but not follicular
      B cells. These results indicated that Gab1 is a unique negative regulator
      specific for TI-2 responses.

PMID- 11994465
TI  - B cells control the migration of a subset of dendritic cells into B cell
      follicles via CXC chemokine ligand 13 in a lymphotoxin-dependent fashion.
AB  - Certain classes of dendritic cells (DCs) meet rare cognate Ag-specific T and B
      cells inside primary B cell follicles for the development of germinal centers.
      However, the mechanisms underlying this coordination are still undefined.
      Cysteine-rich (CR) domain of the mannose receptor (CR-Fc)(+) DCs are a newly
      discovered subset of DCs that migrate rapidly into the primary lymphoid follicles
      from marginal zone after immunization. In this work, we uncover the key role of B
      cells in the establishment of a microenvironment that allows these DCs to be in
      the B cell area in a lymphotoxin (LT)-dependent fashion. CR-Fc(+) DCs are absent
      from the spleens of both LTbetaR- and LTalpha-deficient mice, suggesting that
      signaling by membrane LT is required for the presence of CR-Fc(+) DCs in the
      spleen. Interestingly, analysis of mutant mice that lack T, B, or NK cells
      demonstrates that B cell-derived membrane LT is essential for the unique
      localization of CR-Fc(+) DCs in the spleen. Using bone marrow transfer and ligand
      blocking approaches, we provide evidence that B cell-derived LT acts indirectly
      on CR-Fc(+) DCs through LTbetaR(+) stromal cells. In analogous fashion to certain
      Ag-activated T and B cells, CR-Fc(+) DCs, expressing CXCR5, localize to primary
      lymphoid follicles in response to CXC ligand 13 (B lymphocyte chemoattractant).
      Together, we propose that B cells play a central role in establishing the
      chemotactic gradient that attracts not only Ag-activated T and B cells but also
      Ag-carrying CR-Fc(+) DCs. In turn, CR-Fc(+) DCs and T cells home to B cell
      follicles to interact with B cells in the developing germinal center.

PMID- 11994466
TI  - CD40 ligation in the presence of self-reactive CD8 T cells leads to severe
      immunopathology.
AB  - Previous work has shown that stimulation of APCs via CD40 strongly influences the
      outcome of a CD8 T cell response. In this study, we examined the effect of CD40
      ligation on peripheral tolerance induction of self-reactive CD8 T cells in an
      adoptive transfer model. Naive CD8 T cells from TCR-transgenic (tg) mice specific
      for the gp33 epitope of lymphocytic choriomeningitis virus were tolerized when
      transferred into H8-tg mice expressing the gp33 epitope under the control of a
      MHC class I promoter. However, if the H8 recipient mice were treated with
      agonistic anti-CD40 Abs, TCR-tg cells vigorously proliferated, and induced
      destruction of lymphoid organs and hepatitis. Break of peripheral tolerance
      induction was B cell independent and did not require CD28/B7 interactions. These
      findings provide further in vivo evidence for the crucial role of the activation
      state of the APC in peripheral tolerance induction and suggest the need for
      caution in systemically activating APC via CD40 ligation in the presence of self
      reactive T cells.

PMID- 11994467
TI  - The human V-preB promoter is a target for coordinated activation by early B cell
      factor and E47.
AB  - The development of mature B lymphoid cells involves a highly orchestrated
      regulation of stage- and lineage-specific genes. In this study, we report an
      analysis of the human surrogate L chain VpreB promoter. The promoter has an
      overall homology of 56% to the mouse counterpart and displays a preB cell
      restricted activity in transient transfections in cell lines. The promoter
      harbors three independent binding sites for early B cell factor (EBF) as defined
      by EMSA and supershift experiments. These sites were important for the full
      function of the promoter in a preB cell line, and chromatin immunoprecipitation
      experiments indicate that EBF interacts with the promoter in vivo. In addition to
      this, ectopic expression of EBF induces the activity of a reporter gene under
      control of the VpreB promoter in epithelioid HeLa cells, an effect augmented by
      coexpression of the basic-helix-loop helix transcription factor E47. The ability
      to interact directly with E47 was shared by the promoters controlling the human
      mb-1 and B29 genes. These data indicate that the human VpreB promoter is a direct
      target for activation by EBF and E47 and that functional collaboration between
      these proteins may be of great importance in human B cell development.

PMID- 11994468
TI  - Carcinoembryonic antigen-related cell adhesion molecule 1 expression and
      signaling in human, mouse, and rat leukocytes: evidence for replacement of the
      short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins
      in human leukocytes.
AB  - Carcinoembryonic Ag-related cell adhesion molecule 1 (CEACAM1), the primordial
      carcinoembryonic Ag gene family member, is a transmembrane cell adhesion molecule
      expressed in leukocytes, epithelia, and blood vessel endothelia in humans and
      rodents. As a result of differential splicing, CEACAM1 occurs as several
      isoforms, the two major ones being CEACAM1-L and CEACAM1-S, that have long (L) or
      short (S) cytoplasmic domains, respectively. The L:S expression ratios vary in
      different cells and tissues. In addition to CEACAM1, human but not rodent cells
      express GPI-linked CEACAM members (CEACAM5-CEACAM8). We compared the expression
      patterns of CEACAM1-L, CEACAM1-S, CEACAM6, and CEACAM8 in purified populations of
      neutrophilic granulocytes, B lymphocytes, and T lymphocytes from rats, mice, and
      humans. Human granulocytes expressed CEACAM1, CEACAM6, and CEACAM8, whereas human
      B lymphocytes and T lymphocytes expressed only CEACAM1 and CEACAM6. Whereas
      granulocytes, B cells, and T cells from mice and rats expressed both CEACAM1-L
      and CEACAM1-S in ratios of 2.2-2.9:1, CEACAM1-S expression was totally lacking in
      human granulocytes, B cells, and T cells. Human leukocytes only expressed the L
      isoforms of CEACAM1. This suggests that the GPI-linked CEACAM members have
      functionally replaced CEACAM1-S in human leukocytes. Support for the replacement
      hypothesis was obtained from experiments in which the extracellular signal
      regulated kinases (Erk)1/2 were activated by anti-CEACAM Abs. Thus, Abs against
      CEACAM1 activated Erk1/2 in rat granulocytes, but not in human granulocytes.
      Erk1/2 in human granulocytes could, however, be activated by Abs against CEACAM8.
      We demonstrated that CEACAM1 and CEACAM8 are physically associated in human
      granulocytes. The CEACAM1/CEACAM8 complex in human cells might accordingly play a
      similar role as CEACAM1-L/CEACAM1-S dimers known to occur in rat cells.

PMID- 11994469
TI  - Characterization of a novel killer cell lectin-like receptor (KLRH1) expressed by
      alloreactive rat NK cells.
AB  - NK cells have the ability to recognize and kill MHC-mismatched hemopoietic cells.
      In the present study, strain-specific differences in the rat NK allorecognition
      repertoire were exploited to generate Abs against receptors that may be involved
      in allogeneic responses. A mAb termed STOK9 was selected, and it reacted with
      subsets of NK cells and NKR-P1(+) T cells from certain rat strains possessing
      highly alloreactive NK cells. The STOK9(+) NK subset was broadly alloreactive and
      lysed Con A lymphoblast targets from a range of MHC-mismatched strains. The mAb
      STOK9 precipitated a 75-kDa dimeric glycoprotein from NK lysates. Expression
      cloning revealed that each monomer consisted of 231 aa with limited homology to
      other previously characterized killer cell lectin-like receptors (KLRs). This
      glycoprotein therefore constitutes a novel KLR branch, and it has been termed
      KLRH1. A gene in the central region of the natural killer gene complex on rat
      chromosome 4 encodes KLRH1. A mouse homolog appears to be present as deduced from
      analyses of genomic trace sequences. The function of KLRH1 is unknown, but it
      contains an immunoreceptor tyrosine-based inhibitory motif, suggesting an
      inhibitory function. The MHC haplotype of the host appears to influence KLRH1
      expression, suggesting that it may function as an MHC-binding receptor on subsets
      of NK cells and T lymphocytes.

PMID- 11994470
TI  - Heavy chain V region diversity in the duck-billed platypus (Ornithorhynchus
      anatinus): long and highly variable complementarity-determining region 3
      compensates for limited germline diversity.
AB  - In this work, to study the emergence of the H chain V region repertoire during
      mammalian evolution, we present an analysis of 25 independent H chain V regions
      from a monotreme, the Australian duck-billed platypus, Ornithorhynchus anatinus.
      All the sequences analyzed were found to form a single branch within the clan III
      of mammalian V region sequences in a distance tree. However, compared with a
      classical V gene family this branch was more diversified in sequence. Sequence
      analysis indicates that the apparent lack of diversity in germline V segments is
      well compensated for by relatively long and highly diversified D and N
      nucleotides. In addition, extensive sequence variation was observed in the
      framework region 3. Furthermore, at least five and possibly seven different J
      segments seem to be actively used in recombination. Interestingly, internal
      cysteine bridges in the complementarity-determining region (CDR)3 loop, or
      between the CDR2 and CDR3 loops, are found in approximately 36% of the platypus
      V(H) sequences. Such cysteine bridges have also been observed in cow, camel, and
      shark. Internal cysteine bridges may play a role in stabilizing long and
      diversified CDR3 and thereby have a role in increasing the affinity of the Ab-Ag
      interaction.

PMID- 11994471
TI  - Identification of a novel Ly49 promoter that is active in bone marrow and fetal
      thymus.
AB  - The analysis of several Ly49 genes has identified a tissue-specific promoter
      adjacent to the previously defined first exon. The current study reveals the
      presence of an additional Ly49 promoter (Pro-1) and two noncoding exons upstream
      of the previously defined promoter (Pro-2). DNA sequences homologous to Pro-1 are
      present 4-10 kb upstream of Pro-2 in all Ly49 genes examined, and Pro-1
      transcripts were detected from the Ly49a, e, g, o, and v genes. Pro-1 activity
      can be detected in bone marrow, embryonic thymus, freshly isolated liver NK
      cells, and the murine LNK cell line, but it does not function in adult thymus,
      sorted NK-T cells, spleen NK cells, or the EL-4 T cell line, even though these
      cells express Ly49 proteins. Luciferase reporter assays identified a Pro-1 core
      promoter region that functions in the LNK cell line but not EL-4 cells. The novel
      promoter is not active in mature NK cells, suggesting that Pro-1 represents an
      early Ly49 promoter.

PMID- 11994472
TI  - Kinetic analysis of a unique direct prothrombinase, fgl2, and identification of a
      serine residue critical for the prothrombinase activity.
AB  - fgl2 prothrombinase, by its ability to generate thrombin, has been shown to be
      pivotal to the pathogenesis of viral-induced hepatitis, cytokine-induced fetal
      loss syndrome, and xeno- and allograft rejection. In this study, the molecular
      basis of fgl2 prothrombinase activity was examined in detail. Purified fgl2
      protein generated in a baculovirus expression system had no measurable
      prothrombinase activity, whereas the activity was restored when the purified
      protein was reconstituted into phosphatidyl-L-serine-containing vesicles.
      Reconstituted fgl2 catalyzed the cleavage of human prothrombin to thrombin with
      kinetics consistent with a first order reaction, with an apparent V(max) value of
      6 mol/min/mol fgl2 and an apparent K(m) value for prothrombin of 8.3 microM. The
      catalytic activity was totally dependent on calcium, and factor Va (500 nM)
      enhanced the catalytic efficiency of fgl2 by increasing the apparent V(max) value
      to 3670 mol/min/mol fgl2 and decreasing the apparent K(m) value for prothrombin
      to 7.2 microM. By a combination of site-directed mutagenesis and production of
      truncated proteins, it was clearly shown that residue Ser(89) was critical for
      the prothrombinase activity of fgl2. Furthermore, fgl2 prothrombinase activity
      was not inhibited by antithrombin III, soybean trypsin inhibitor, 4
      aminobenzamidine, aprotinin, or phenylmethylsulfonyl fluoride, whereas
      diisopropylfluorophosphate completely abrogated the activity. In this work we
      provide direct evidence that fgl2 cleaves prothrombin to thrombin consistent with
      serine protease activity and requires calcium, phospholipids, and factor Va for
      its full activity.

PMID- 11994473
TI  - Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via
      enhancement of the heat shock element binding activity of heat shock
      transcription factor 1.
AB  - With most immunological reactions, tissue fibrosis, collagen overproduction
      caused by immune cytokines, is inevitably associated. Among the various immune
      cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular
      chaperon and is essential for secretion of procollagen from cells. Induction of
      HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and
      mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its
      effect on HSP47 has not been elucidated. In the present study, using human
      embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL
      1beta induced HSP47 synthesis. We then revealed that the binding of the heat
      shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by
      both cytokines. We further demonstrated that trimer formation of HSF1, which is
      essential for its binding to HSE, was induced by these cytokines. The enhancement
      of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a
      combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to
      induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in
      the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate
      for molecular targeting in controlling tissue fibrosis, given that both principal
      fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its
      induction through HSF1 trimerization.

PMID- 11994474
TI  - Antigenic topology of chlamydial PorB protein and identification of targets for
      immune neutralization of infectivity.
AB  - The outer membrane protein PorB is a conserved chlamydial protein that functions
      as a porin and is capable of eliciting neutralizing Abs. A topological antigenic
      map was developed using overlapping synthetic peptides representing the Chlamydia
      trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic
      determinants were surface accessible, monospecific antisera were raised to the
      PorB peptides and were used in dot-blot and ELISA-based absorption studies with
      viable chlamydial elementary bodies (EBs). The ability of the surface-accessible
      antigenic determinants to direct neutralizing Ab responses was investigated using
      standardized in vitro neutralization assays. Four major antigenic clusters
      corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2
      4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were
      identified. Collectively, the EB absorption and dot-blot assays established that
      the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs.
      Peptide-specific antisera raised to the surface-accessible Ags neutralized
      chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides
      representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization
      of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by
      synthetic peptides representing the surface-exposed PorB antigenic determinants.
      These findings demonstrate that PorB Ags may be useful for development of
      chlamydial vaccines.

PMID- 11994475
TI  - Costimulation of host T lymphocytes by a trypanosomal trans-sialidase:
      involvement of CD43 signaling.
AB  - Trans-sialidase is a membrane-bound and shed sialidase from Trypanosoma cruzi,
      the protozoan parasite responsible for Chagas disease. We investigated the role
      of soluble trans-sialidase on host CD4+ T cell activation. Trans-sialidase
      activated naive CD4+ T cells in vivo. Both enzymatically active and inactive
      recombinant trans-sialidases costimulated CD4+ T cell activation in vitro.
      Costimulation resulted in increased mitogen-activated protein kinase activation,
      proliferation, and cytokine synthesis. Furthermore, active and inactive trans
      sialidases blocked activation-induced cell death in CD4+ T cells from T. cruzi
      infected mice. By flow cytometry, inactive trans-sialidase bound the highly
      sialylated surface Ag CD43 on host CD4+ T cells. Both costimulatory and
      antiapoptotic effects of trans-sialidases required CD43 signaling. These results
      suggest that trans-sialidase family proteins are involved in exacerbated host T
      lymphocyte responses observed in T. cruzi infection.

PMID- 11994476
TI  - Expansion of NK cells with reduction of their inhibitory Ly-49A, Ly-49C, and Ly
      49G2 receptor-expressing subsets in a murine helminth infection: contribution to
      parasite control.
AB  - Natural killer cell-associated direct cytotoxicity and cytokine production are
      crucial mechanisms for early innate host resistance against viruses, bacteria, or
      protozoa. The engagement of inhibitory NK cell receptors can influence host
      responses to viruses. However, these receptors have not been investigated to date
      in parasitic infections, and little is known about the role of NK cells in the
      defense against helminths. Therefore, we have correlated the frequencies of cells
      expressing the pan-NK marker DX5 and subsets bearing inhibitory Ly-49 receptors
      with worm survival and cytokine production during infection with Litomosoides
      sigmodontis in BALB/c mice (H2(d)), the only fully permissive model of
      filariasis. A marked influx of DX5(+)/CD3(-) NK cells and DX5(+)/CD3(+) T cells
      into the pleural cavity, where the parasites were located, was observed. The
      frequency of pleural NK cells expressing the H2(d)-reactive inhibitory receptors
      Ly-49A, Ly-49C, or Ly-49G2 declined most strongly compared with spleen and blood.
      In the peripheral blood, longitudinal analysis revealed an early and stable
      reduction of Ly-49C(+) and Ly-49G2(+) NK cells, a subsequent significant increase
      of the entire NK cell and DX5(+)/CD3(+) T cell populations, and a reduction in
      the Ly-49A(+) subset. The in vivo depletion of NK cells strongly enhanced the
      worm load and influenced IL-4 and IL-5 plasma levels. These data demonstrate a
      new role for NK cells in the host defense against filariae and, for the first
      time, alterations of Ly-49 receptor-expressing NK cell subsets in a parasitic
      infection.

PMID- 11994477
TI  - Critical role of signaling through IL-1 receptor for development of arthritis and
      sepsis during Staphylococcus aureus infection.
AB  - IL-1R-deficient mice (IL-1R(-/-)) and their wild-type controls (IL-1R(+/+)) were
      i.v. inoculated with 1 x 10(7) or 10(6) Staphylococcus aureus per mouse to mimic
      bacterial sepsis and septic arthritis. The disease outcome was severely worsened
      in the IL-1R(-/-) mice as compared with IL-1R(+/+) mice. Indeed, 3 days after
      inoculation of 10(7) S. aureus per mouse 84% of IL-1R(-/-) mice displayed
      clinical signs of septicemia as compared with none of the IL-1R(+/+) mice. On day
      9 after inoculation with 10(6) S. aureus per mouse 75% of the IL-1R(-/-) mice
      were dead as compared with none of the IL-1R(+/+) mice. Also, the number of
      staphylococci in circulation was 25- to 30-fold increased in IL-1R(-/-) mice as
      compared with IL-1R(+/+) mice, the most probable reason for the outcome. The
      frequency and severity of septic arthritis were significantly increased in IL-1R(
      /-) mice, as compared with IL-1R(+/+) mice, following i.v. inoculation of
      staphylococci. This was probably due to an increased accumulation of bacteria in
      the joints of IL-1R(-/-) mice as compared with their wild-type controls.
      Interestingly, while serum levels of IL-18 in IL-1R(-/-) mice were significantly
      lower than in IL-1R(+/+) mice 24 h after inoculation of S. aureus, both IL-18 and
      IL-1beta were significantly increased in IL-1R(-/-) vs IL-1R(+/+) mice 4 days
      after the bacterial inoculation. In conclusion, IL-1R signaling plays a crucial
      role in host protection during systemic S. aureus infection as seen by the fatal
      outcome of S. aureus sepsis and arthritis in IL-1R-deficient mice.

PMID- 11994478
TI  - Complement C2 receptor inhibitor trispanning and the beta-chain of C4 share a
      binding site for complement C2.
AB  - Complement C2 receptor inhibitor trispanning (CRIT) of the Schistosoma parasite
      binds human C2 via the C2a segment. The receptor in vivo functions as C2 decoy
      receptor by directly competing with C4b for binding to C2. As a result, CRIT is
      able to limit the extent of classical pathway (CP) C3 convertase formation. We
      report that the CRIT-extracellular domain 1 (ed1) peptide inhibits CP-mediated
      complement activation with an ICH(50) of approximately 0.1 microM, the C-terminal
      11 aa of CRIT-ed1, named H17, even more effectively. The beta-chain region F222
      Y232 of C4 shares 55% identity and 73% similarity with H17. Peptides based on
      this region also inhibit CP in a dose-dependent manner. As further evidence of C2
      binding we showed CRIT-ed1 peptides and homologous C4 beta-chain peptides to
      inhibit complement in C2 hemolytic assays. We have predicted C4 beta-c F222-Y232
      as a C2 binding site which we have termed the CRIT-ed1 domain, and the sequence
      [F/H]EVKX(4/5)P as a consensus C2-binding sequence. Anti-CRIT-ed1 cross-reacts
      with the C4 beta-chain and F222EVKITPGKPY232 appears to be the key epitope
      recognized by this Ab. Furthermore, anti-CRIT-ed1 was found to inhibit CP
      activation in a total hemolytic assay. We believe that Schistosoma CRIT-ed1, as
      well as C4 beta-chain peptides based on the CRIT-ed1 domain, function as
      interface peptides. These peptides, based on C2-binding sequences in CRIT, or C4,
      competitively inhibit the binding of C2 to C4b and thus limit the activation of
      C. The C4 peptides, unlike CRIT-ed1, did not inhibit the cleavage of C2 by C1s.

PMID- 11994479
TI  - Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q.
AB  - It has been suggested that the human C1qRp is a receptor for the complement
      component C1q; however, there is no direct evidence for an interaction between
      C1q and C1qRp. In this study, we demonstrate that C1q does not show enhanced
      binding to C1qRp-transfected cells compared with control cells. Furthermore, a
      soluble recombinant C1qRp-Fc chimera failed to interact with immobilized C1q. The
      proposed role of C1qRp in the phagocytic response in vivo is also unsupported in
      that we demonstrate that this molecule is not expressed by macrophages in a
      variety of human tissues and the predominant site of expression is on endothelial
      cells. Studies on the rodent homolog of C1qRp, known as AA4, have suggested that
      this molecule may function as an intercellular adhesion molecule. Here we show
      that C1qRp is the Ag recognized by several previously described mAbs, mNI-11 and
      two anti-CD93 Abs (clones X2 and VIMD2b). Interestingly, mNI-11 (Fab') has been
      shown to promote monocyte-monocyte and monocyte-endothelial cell adhesive
      interactions. We produced a recombinant C1qRp-Fc chimera containing the C-type
      lectin-like domain of C1qRp and found specific binding to vascular endothelial
      cells in sections of inflamed human tonsil, indicating the presence of a C1qRp
      ligand at this site. This interaction was Ca(2+) independent and was not blocked
      by our anti-C1qRp mAb BIIG-4, but was blocked by the proadhesive mAb mNI-11.
      Collectively, these data indicate that C1qRp is not a receptor for C1q, and they
      support the emerging role of C1qRp (here renamed CD93) in functions relevant to
      intercellular adhesion.

PMID- 11994480
TI  - Receptor-mediated monitoring of tissue well-being via detection of soluble
      heparan sulfate by Toll-like receptor 4.
AB  - Perturbations to the well-being of tissues in plants and invertebrates generate
      fragments of endogenous molecules that are recognized by innate immune receptors.
      Vertebrates have homologous receptors on specialized cells such as dendritic
      cells, but whether these receptors respond to fragments of endogenous molecules
      is not known. We tested the idea that Toll-like receptors on dendritic cells
      might recognize polysaccharide fragments of heparan sulfate proteoglycan.
      Dendritic cells were found to mature in response to heparan sulfate as measured
      by costimulatory protein expression, morphology, and T lymphocyte stimulation,
      but this maturation was absent when Toll-like receptor 4 was mutated or
      inhibited. These findings suggest that Toll-like receptors in vertebrates may
      monitor tissue well-being by recognizing fragments of endogenous macromolecules.

PMID- 11994481
TI  - Two msbB genes encoding maximal acylation of lipid A are required for invasive
      Shigella flexneri to mediate inflammatory rupture and destruction of the
      intestinal epithelium.
AB  - Shigella flexneri is a Gram-negative pathogen that invades and causes
      inflammatory destruction of the human colonic epithelium, thus leading to bloody
      diarrhea and dysentery. A type III secretion system that delivers effector
      proteins into target eukaryotic cells is largely responsible for cell and tissue
      invasion. However, the respective role of this invasive phenotype and of lipid A,
      the endotoxin of the Shigella LPS, in eliciting the inflammatory cascade that
      leads to rupture and destruction of the epithelial barrier, was unknown. We
      investigated whether genetic detoxification of lipid A would cause significant
      alteration in pathogenicity. We showed that S. flexneri has two functional msbB
      genes, one carried by the chromosome (msbB1) and the other by the virulence
      plasmid (msbB2), the products of which act in complement to produce full acyl-oxy
      acylation of the myristate at the 3' position of the lipid A glucosamine
      disaccharide. A mutant in which both the msbB1 and msbB2 genes have been
      inactivated was impaired in its capacity to cause TNF-alpha production by human
      monocytes and to cause rupture and inflammatory destruction of the epithelial
      barrier in the rabbit ligated intestinal loop model of shigellosis, indicating
      that lipid A plays a significant role in aggravating inflammation that eventually
      destroys the intestinal barrier. In addition, neutralization of TNF-alpha during
      invasion by the wild-type strain strongly impaired its ability to cause rupture
      and inflammatory destruction of the epithelial lining, thus indicating that TNF
      alpha is a major effector of epithelial destruction by Shigella.

PMID- 11994482
TI  - Regulation of Toll-like receptor 4 expression in the lung following hemorrhagic
      shock and lipopolysaccharide.
AB  - The Toll-like receptor 4 (TLR4) has recently been shown to function as the major
      upstream sensor for LPS. In this study, a rodent model of lung injury following
      resuscitated hemorrhagic shock was used to examine the regulation of TLR4 gene
      and protein expression in vivo and in vitro. Intratracheal LPS alone induced a
      rapid reduction in whole lung TLR4 mRNA, an effect which is also observed in
      recovered alveolar macrophages. This effect appeared to be due to a lowering of
      TLR4 mRNA stability by approximately 69%. By contrast, while shock/resuscitation
      alone had no effect on TLR4 mRNA levels, it markedly altered the response to LPS.
      Specifically, antecedent shock prevented the LPS-induced reduction in TLR4 mRNA
      levels. This reversal was explained by the ability of prior resuscitated shock
      both to prevent the destabilization of TLR4 mRNA by LPS and also to augment LPS
      stimulated TLR4 gene transcription compared with LPS alone. Oxidant stress
      related to shock/resuscitation appeared to contribute to the regulation of TLR4
      mRNA, because supplementation of the resuscitation fluid with the antioxidant N
      acetylcysteine reversed the ability of shock/resuscitation to preserve TLR4 mRNA
      levels following LPS. TLR4 protein levels in whole lung mirrored the changes seen
      for TLR4 mRNA. Considered in aggregate, these data suggest that levels of tlr4
      expression are controlled both transcriptionally as well as posttranscriptionally
      through altered mRNA stability and that antecedent shock/resuscitation, a form of
      global ischemia/reperfusion, might influence regulation of this gene.

PMID- 11994483
TI  - Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory
      gene expression and reduce the severity of dextran sodium sulfate-induced
      colitis.
AB  - The anti-inflammatory eicosanoid lipoxin A(4) (LXA(4)), aspirin-triggered 15-epi
      LXA(4), and their stable analogs down-regulate IL-8 secretion and subsequent
      recruitment of neutrophils by intestinal epithelia. In an effort to elucidate the
      mechanism by which these lipid mediators modulate cellular proinflammatory
      programs, we surveyed global epithelial gene expression using cDNA microarrays.
      LXA(4) analog alone did not significantly affect expression of any of the >7000
      genes analyzed. However, LXA(4) analog pretreatment attenuated induction of
      approximately 50% of the 125 genes up-regulated in response to the
      gastroenteritis-causing pathogen Salmonella typhimurium. A major subset of genes
      whose induction was reduced by LXA(4) analog pretreatment is regulated by NF
      kappaB, suggesting that LXA(4) analog was influencing the activity of this
      transcription factor. Nanomolar concentrations of LXA(4) analog reduced NF-kappaB
      mediated transcriptional activation in a LXA(4) receptor-dependent manner and
      inhibited induced degradation of IkappaBalpha. LXA(4) analog did not affect
      earlier stimulus-induced signaling events that lead to IkappaBalpha degradation,
      such as S. typhimurium-induced epithelial Ca(2+) mobilization or TNF-alpha
      induced phosphorylation of IkappaBalpha. To establish the in vivo relevance of
      these findings, we examined whether LXA(4) analogs could affect intestinal
      inflammation in vivo using the mouse model of DSS-induced inflammatory colitis.
      Oral administration of LXA(4) analog (15-epi-16-para-fluoro-phenoxy-LXA(4), 10
      microg/day) significantly reduced the weight loss, hematochezia, and mortality
      that characterize DSS colitis. Thus, LXA(4) analog-mediated down-regulation of
      proinflammatory gene expression via inhibition of the NF-kappaB pathway can be
      therapeutic for diseases characterized by mucosal inflammation.

PMID- 11994484
TI  - The chemokine stromal cell-derived factor-1 alpha modulates alpha 4 beta 7
      integrin-mediated lymphocyte adhesion to mucosal addressin cell adhesion molecule
      1 and fibronectin.
AB  - The interaction between the integrin alpha(4)beta(7) and its ligand, mucosal
      addressin cell adhesion molecule-1, on high endothelial venules represents a key
      adhesion event during lymphocyte homing to secondary lymphoid tissue. Stromal
      cell-derived factor-1alpha (SDF-1alpha) is a chemokine that attracts T and B
      lymphocytes and has been hypothesized to be involved in lymphocyte homing. In
      this work we show that alpha(4)beta(7)-mediated adhesion of CD4(+) T lymphocytes
      and the RPMI 8866 cell line to mucosal addressin cell adhesion molecule-1 was up
      regulated by SDF-1alpha in both static adhesion and cell detachment under shear
      stress assays. Both naive and memory phenotype CD4(+) T cells were targets of SDF
      1alpha-triggered increased adhesion. In addition, SDF-1alpha augmented
      alpha(4)beta(7)-dependent adhesion of RPMI 8866 cells to connecting segment-1 of
      fibronectin. While pertussis toxin totally blocked chemotaxis of CD4(+) and RPMI
      8866 cells to SDF-1alpha, enhanced alpha(4)beta(7)-dependent adhesion triggered
      by this chemokine was partially inhibited, indicating the participation of
      Galpha(i)-dependent as well as Galpha(i)-independent signaling. Accordingly, we
      show that SDF-1alpha induced a rapid and transient association between its
      receptor CXCR4 and Galpha(i), whereas association of pertussis toxin-insensitive
      Galpha(13) with CXCR4 was slower and of a lesser extent. SDF-1alpha also
      activated the small GTPases RhoA and Rac1, and inhibition of RhoA activation
      reduced the up-regulation of alpha(4)beta(7)-mediated lymphocyte adhesion in
      response to SDF-1alpha, suggesting that activation of RhoA could play an
      important role in the enhanced adhesion. These data indicate that up-regulation
      by SDF-1alpha of lymphocyte adhesion mediated by alpha(4)beta(7) could contribute
      to lymphocyte homing to secondary lymphoid tissues.

PMID- 11994485
TI  - IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and
      airway inflammation in a mouse model of asthma.
AB  - Allergic asthma is an inflammatory disease of the airways characterized by
      eosinophilic inflammation and airway hyper-reactivity. Cytokines and chemokines
      specific for Th2-type inflammation predominate in asthma and in animal models of
      this disease. The role of Th1-type inflammatory mediators in asthma remains
      controversial. IFN-gamma-inducible protein 10 (IP-10; CXCL10) is an IFN-gamma
      inducible chemokine that preferentially attracts activated Th1 lymphocytes. IP-10
      is up-regulated in the airways of asthmatics, but its function in asthma is
      unclear. To investigate the role of IP-10 in allergic airway disease, we examined
      the expression of IP-10 in a murine model of asthma and the effects of
      overexpression and deletion of IP-10 in this model using IP-10-transgenic and IP
      10-deficient mice. Our experiments demonstrate that IP-10 is up-regulated in the
      lung after allergen challenge. Mice that overexpress IP-10 in the lung exhibited
      significantly increased airway hyperreactivity, eosinophilia, IL-4 levels, and
      CD8(+) lymphocyte recruitment compared with wild-type controls. In addition,
      there was an increase in the percentage of IL-4-secreting T lymphocytes in the
      lungs of IP-10-transgenic mice. In contrast, mice deficient in IP-10 demonstrated
      the opposite results compared with wild-type controls, with a significant
      reduction in these measures of Th2-type allergic airway inflammation. Our results
      demonstrate that IP-10, a Th1-type chemokine, is up-regulated in allergic
      pulmonary inflammation and that this contributes to the airway hyperreactivity
      and Th2-type inflammation seen in this model of asthma.

PMID- 11994486
TI  - Localized exocytosis of primary (lysosomal) granules during phagocytosis: role of
      Ca2+-dependent tyrosine phosphorylation and microtubules.
AB  - The uptake and killing of bacteria by human neutrophils are dependent on the
      fusion of secretory granules with forming phagosomes. The earliest component of
      exocytosis was found to precede phagosome closure, so that granular membrane
      constituents were detectable on the plasmalemma. We show that during phagocytosis
      of IgG-opsonized particles, this early secretory response is highly polarized in
      the case of primary granules, but less so for specific granules. The vectorial
      discharge of primary granules was dependent on calcium, but no evidence was found
      that calcium is involved in determining the polarity of exocytosis. In
      particular, a redistribution of endomembrane calcium stores toward forming
      phagosomes could not be detected. Polarized granule exocytosis was accompanied by
      focal tyrosine phosphorylation and actin polymerization, although the latter was
      not required for the response. Instead, microtubules seemed to contribute to the
      vectorial nature of the response. During particle ingestion, the microtubule
      organizing center relocated toward forming phagosomes, and colchicine treatment
      altered the pattern of exocytosis, reducing its directionality. We hypothesize
      that the focal activation of tyrosine kinases generates localized signals that
      induce exocytosis in a calcium-dependent manner, and that reorientation of
      microtubules facilitates preferential delivery of granules toward the forming
      phagosome.

PMID- 11994487
TI  - Mast cell-derived TNF-alpha primes sensory nerve endings in a pulmonary
      hypersensitivity reaction.
AB  - TNF-alpha is a cytokine associated with inflammatory diseases, including asthma.
      Increased levels of TNF-alpha were found in the bronchoalveolar lavage fluid of
      mice undergoing a dinitrofluorobenzene (DNFB)-induced non-IgE-mediated pulmonary
      hypersensitivity reaction. We report in this work that TNF-alpha increases the
      susceptibility of sensory neurons to dinitrobenzene sulfonic acid (DNS) and
      capsaicin, leading to a tracheal vascular hyperpermeability response in DNFB
      sensitized and DNS-challenged mice. mAb against TNF-alpha or the TNFR1 inhibited
      this hyperpermeability response in DNFB-sensitized and DNS-challenged mice.
      Furthermore, the hyperpermeability response after DNS challenge was abolished in
      DNFB-sensitized mast cell-deficient WBB6F(1)-W/W(V) mice. These animals showed a
      remarked decrease of TNF-alpha bronchoalveolar lavage fluid levels after a single
      DNS challenge. The hyperpermeability response after DNS challenge was regained in
      mast cell-deficient mice after mast cell reconstitution. These findings indicate
      a prominent role for TNF-alpha and its TNFR1 in the DNFB-induced tracheal
      hyperpermeability response. We propose that a priming effect of mast cell-derived
      TNF-alpha on the sensory neurons could be the mechanism of action of TNF-alpha in
      the vascular hyperpermeability response in tracheas of mice undergoing a
      pulmonary hypersensitivity reaction.

PMID- 11994488
TI  - Inhibition of mitogen-activated protein kinase signaling by chloroquine.
AB  - Previously, we demonstrated that the anti-inflammatory drug chloroquine (CQ)
      inhibited LPS-induced TNF-alpha transcription. To define further the mechanism of
      CQ, we studied the effect of this drug on mitogen-activated protein kinase
      signaling pathways involved in regulation of TNF production. CQ interfered with
      phosphorylation of extracellular signal-regulated kinases (ERK)1/2 and the ERK
      activating kinases mitogen-activating protein/ERK kinase (MEK)1/2. Both CQ and
      PD98059, a MEK1 inhibitor, reduced luciferase reporter activity driven by human
      TNF promoter sequences. However, CQ appeared to mediate these effects by
      deactivating Raf, the upstream activator of MEK. These findings were supported by
      functional data demonstrating that CQ and PD98059 interfered with TNF expression
      in several human and murine cell types while neither inhibitor blocked TNF
      production in murine RAW264.7 macrophages, a cell line that does not require MEK
      ERK signaling for TNF production. Finally, we evaluated whether CQ could
      sensitize HeLa cells to undergo anti-Fas-mediated apoptosis, an effect observed
      when ERK activation is interrupted in this cell line. CQ rendered HeLa cells
      sensitive to anti-Fas treatment in a manner similar to PD98059. Taken together,
      these data argue that therapeutic concentrations of CQ interfere with ERK
      activation by a novel mechanism, an effect that could be responsible, at least in
      part, for the potent anti-inflammatory effects of this drug.

PMID- 11994489
TI  - Inflammatory microcrystals alter the functional phenotype of human osteoblast
      like cells in vitro: synergism with IL-1 to overexpress cyclooxygenase-2.
AB  - Chronic crystal-associated arthropathies such as gout and pseudogout can lead to
      local bone destruction. Because osteoblasts, which orchestrate bone remodeling
      via soluble factors and cell-to-cell interactions, have been described in contact
      with microcrystals, particularly in uratic foci of gout, we hypothesized that
      microcrystals of monosodium urate monohydrate (MSUM) and of calcium pyrophosphate
      dihydrate (CPPD) could alter osteoblastic functions. MSUM and CPPD adhered to
      human osteoblastic cells (hOB) in vitro and were partly phagocytized as shown by
      scanning electron microscopy. MSUM and CPPD dose-dependently stimulated the
      production of PGE(2) in hOB as assessed by enzyme immunoassay, a response that
      was synergistically enhanced in the presence of IL-1. The mechanism of this
      synergism was, at least in part, at the level of the expression of cyclooxygenase
      2 as evaluated by immunoblot analysis. MSUM and CPPD also stimulated the
      expression of IL-6 and IL-8 and reduced the 1,25-dihydroxyvitamin D(3)-induced
      activity of alkaline phosphatase and osteocalcin in hOB (with no synergism with
      IL-1). MSUM- or CPPD-stimulated expression of IL-6 in hOB pretreated with the
      selective cyclooxygenase-2 inhibitor NS-398 was increased, unlike that induced by
      IL-1 alone which was partially reduced. MSUM-, CPPD- or IL-1-induced expression
      of IL-8 was unchanged by pretreating hOB with NS-398. These results suggest that
      inflammatory microcrystals alter the normal phenotype of hOB, redirecting them
      toward reduced bone formation and amplified osteoblast-mediated bone resorption,
      abnormalities that could play a role in the bone destruction associated with
      chronic crystal-induced arthritis.

PMID- 11994490
TI  - A proinflammatory role for the cyclopentenone prostaglandins at low micromolar
      concentrations: oxidative stress-induced extracellular signal-regulated kinase
      activation without NF-kappa B inhibition.
AB  - An anti-inflammatory role and therapeutic potential for cyclopentenone PGs
      (cyPGs) has been suggested, based on observations that levels of cyPGs in
      exudates increase during the resolution phase of inflammation, and that exogenous
      cyPGs may attenuate the inflammatory response in vivo and in vitro mainly through
      inhibition of NF-kappaB, a critical activator of inflammatory gene expression.
      However, exogenous cyPGs inhibit NF-kappaB only at concentrations substantially
      higher than those of endogenous cyPGs present in inflammatory fluids, thus
      challenging the hypothesis that cyPGs are naturally occurring inhibitors of
      inflammation and suggesting that cyPGs at low concentrations might have
      previously unappreciated effects. In this study, using various cell types, we
      report that cyPGs, when used at concentrations substantially lower than required
      for NF-kappaB inhibition (viz, low micromolar concentrations), significantly
      potentiate the inflammatory response to TNF-alpha. At these concentrations, cyPGs
      induce production of reactive oxygen species, thereby synergizing with TNF-alpha
      to activate the extracellular signal-regulated kinase 1/2, an activation which in
      turn potentiates proinflammatory cytokine expression at both transcriptional and
      posttranscriptional levels. Our study establishes a proinflammatory role for
      cyPGs at low micromolar concentrations, raises the possibility that cyPGs do not
      act as physiologic anti-inflammatory mediators, and questions the therapeutic
      potential of these compounds.

PMID- 11994491
TI  - Immune responses to small nuclear ribonucleoproteins: antigen-dependent distinct
      B cell epitope spreading patterns in mice immunized with recombinant polypeptides
      of small nuclear ribonucleoproteins.
AB  - Complex patterns of autoantibody reactivities with the small nuclear
      ribonucleoproteins (snRNPs) are observed in systemic lupus erythematosus. To
      investigate the role of individual snRNP components in the initiation and
      diversification of anti-snRNP Ab responses, we immunized A/J mice with
      recombinant Smith D (SmD), Smith B (SmB), and A ribonucleoprotein (A-RNP) with
      alum as adjuvant. Sera at different time points after initial immunizations were
      analyzed by Western blot and immunoprecipitation assays. In SmD-immunized mice,
      specific Abs to A-RNP and SmB were generated by 2 mo postimmunization, in
      addition to the detection of cross-reactive Abs between the immunogen and other
      snRNPs. Whereas Abs reactive with the immunogen decreased by 5 mo, Abs capable of
      immunoprecipitating A-RNP and SmB increased. In SmB-immunized mice, specific Abs
      to A-RNP were readily detectable, in addition to cross-reactive Abs. In contrast,
      A-RNP-immunized mice had only cross-reactive Abs to SmB without detectable Abs to
      SmD. However, in these mice, specific Abs to the 70-kDa protein were generated.
      Abs, which precipitated the native snRNP particle, were generated in all three
      groups of the immunized mice. Our results show that different initiating Ags from
      the same multiprotein antigenic complex induce distinct patterns of epitope
      spreading to proteins within that complex. These data have significant
      implications for the mechanisms of autoantibody diversification in systemic lupus
      erythematosus.

PMID- 11994492
TI  - Anatomic localization of immature and mature dendritic cells in an ectopic
      lymphoid organ: correlation with selective chemokine expression in rheumatoid
      synovium.
AB  - It remains to be clarified whether dendritic cells (DC) reach the rheumatoid
      arthritis (RA) synovium, considered an ectopic lymphoid organ, as mature cells or
      undergo local maturation. We characterized by immunohistochemistry the DC subsets
      and used tonsils as a control. Immature and mature DC were defined by CD1a and DC
      lysosome-associated membrane protein/CD83 expression, respectively. Immature DC
      were mainly detected in the lining layer in RA synovium. Mature DC were
      exclusively detected in the lymphocytic infiltrates. The DC-lysosome-associated
      membrane protein/CD1a ratio was 1.1 in RA synovium and 5.3 in tonsils, suggesting
      the relative accumulation of immature DC in RA synovium. We then focused on the
      expression of CCL20/CCR6 and CCL19/CCR7, CCL21/CCR7 chemokine/receptor complex,
      which control immature and mature DC migration respectively. A close association
      was observed between CCL20-producing cells and CD1a(+) cells, suggesting the
      contribution of CCL20 to CCR6(+) cell homing. Conversely, CCL21 and CCL19
      expression was only detected in perivascular infiltrates. The association among
      CCL19/21-producing cells, CCR7 expression, and mature DC accumulation is in line
      with the roles of these chemokines in mature CCR7(+) DC homing to lymphocytic
      infiltrates. The role of DC in disease initiation and perpetuation makes
      chemokines involved in DC migration a potential therapeutic target.

PMID- 11994493
TI  - p38 mitogen-activated protein kinase is activated and linked to TNF-alpha
      signaling in inflammatory bowel disease.
AB  - Inflammatory bowel diseases (IBD)--Crohn's disease and ulcerative colitis--are
      relapsing chronic inflammatory disorders which involve genetic, immunological,
      and environmental factors. The regulation of TNF-alpha, a key mediator in the
      inflammatory process in IBD, is interconnected with mitogen-activated protein
      kinase pathways. The aim of this study was to characterize the activity and
      expression of the four p38 subtypes (p38alpha-delta), c-Jun N-terminal kinases
      (JNKs), and the extracellular signal-regulated kinases (ERK)1/2 in the inflamed
      intestinal mucosa. Western blot analysis revealed that p38alpha, JNKs, and ERK1/2
      were significantly activated in IBD, with p38alpha showing the most pronounced
      increase in kinase activity. Protein expression of p38 and JNK was only
      moderately altered in IBD patients compared with normal controls, whereas ERK1/2
      protein was significantly down-regulated. Immunohistochemical analysis of
      inflamed mucosal biopsies localized the main expression of p38alpha to lamina
      propria macrophages and neutrophils. ELISA screening of the supernatants of
      Crohn's disease mucosal biopsy cultures showed that incubation with the p38
      inhibitor SB 203580 significantly reduced secretion of TNF-alpha. In vivo
      inhibition of TNF-alpha by a single infusion of anti-TNF-alpha Ab (infliximab)
      resulted in a highly significant transient increase of p38alpha activity during
      the first 48 h after infusion. A significant infliximab-dependent p38alpha
      activation was also observed in THP-1 myelomonocytic cells. In human monocytes,
      infliximab enhanced TNF-alpha gene expression, which could be inhibited by SB
      203580. In conclusion, p38alpha signaling is involved in the pathophysiology of
      IBD.

PMID- 11994494
TI  - Intact active bone transplantation synergizes with anti-CD40 ligand therapy to
      induce B cell tolerance.
AB  - Blockade of T cell costimulatory pathways can result in the prolongation of
      allograft survival through the suppression of Th1 responses; however, late
      allograft rejection is usually accompanied by an emerging allograft-specific
      humoral response. We have recently determined that intact active bone (IAB)
      fragments transplanted under the kidney capsule can synergize with transient anti
      CD40 ligand (CD40L) treatment to induce robust donor-specific allograft tolerance
      and suppress the alloantibody response. In this study, we take advantage of the
      ability of galactosyltransferase-deficient knockout (GT-Ko) mice to respond to
      the carbohydrate epitope, galactose-alpha1,3-galactose (Gal), to investigate
      whether IAB plus transient anti-CD40L therapy directly tolerize B cell responses.
      GT-Ko mice tolerized to Gal-expressing C3H hearts and IAB plus transient anti
      CD40L therapy were challenged with pig kidney membranes that express high levels
      of Gal. The anti-Gal IgM and IgG responses were significantly suppressed in IAB
      tolerant mice compared with controls, while the non-Gal anti-pig Ab responses
      were comparable. The anti-pig T cell cytokine response (IFN-gamma and IL-4) was
      comparable in IAB-tolerant and control mice. The tolerant state for the anti-Gal
      IgM response could be reversed with repeated immunization, whereas the tolerant
      state for the IgG response was robust and resisted repeated immunization. These
      observations provide an important proof-of-concept that adjunct therapies can
      synergize with anti-CD40L Abs to tolerize B cell responses independent of their
      effects on T cells. This model, which does not require mixed chimerism, provides
      a unique opportunity for investigating the mechanism of peripheral tolerance in a
      clinically relevant population of carbohydrate-specific B cells.

PMID- 11994495
TI  - Characterization of drug-specific T cells in phenobarbital-induced eruption.
AB  - Phenobarbital has a high potential to elicit adverse reactions including severe
      skin eruptions and systemic involvements among the worldwide-prescribed drugs.
      Although phenobarbital hypersensitivity is thought to be mediated by T cells
      specific to the drug, its precise mechanism remains not fully elucidated. To
      characterize T cells reactive with phenobarbital, we generated drug-specific T
      cell clones and lines from PBMCs of patients with phenobarbital hypersensitivity
      showing various degrees of cutaneous and extracutaneous involvements. Although
      the TCR Vbeta repertoire and phenotype in the T cell clones/T cell lines were
      heterogeneous among the patients, Vbeta13.1(+) and Vbeta5.1(+) clones or lines
      were raised from the individuals examined who possessed different HLA haplotypes.
      Histopathological examination suggested that Vbeta5.1(+)CD8(+) T cells and
      Vbeta13.1(+) T cells played a role in cutaneous and extracutaneous involvements,
      respectively. A Vbeta13.1(+)CD4(+) clone was found to proliferate in response to
      the Ag with processing-impaired, fixed APCs. Most of the clones and lines
      belonged to the Th2 phenotype, producing IL-4 and IL-5 but not IFN-gamma upon
      phenobarbital stimulation. Clones/lines with Th1 or Th0 phenotypes also
      constituted minor populations. These observations clearly indicate the
      heterogeneity and a marked individual deviation of reactive T cell subsets among
      the patients in terms of CD4/8 phenotype, Vbeta repertoire, Ag recognition
      pattern, and cytokine production; and thus provide evidence whereby each
      pathogenic T cell subset contributes to special elements of clinical
      presentation.

PMID- 11994496
TI  - Molecular mechanisms for gender differences in susceptibility to T cell-mediated
      autoimmune diabetes in nonobese diabetic mice.
AB  - Nonobese diabetic (NOD) mice spontaneously develop diabetes with a strong female
      prevalence; however, the mechanisms for this gender difference in susceptibility
      to T cell-mediated autoimmune diabetes are poorly understood. This investigation
      was initiated to find mechanisms by which sex hormones might affect the
      development of autoimmune diabetes in NOD mice. We examined the expression of IFN
      gamma, a characteristic Th1 cytokine, and IL-4, a characteristic Th2 cytokine, in
      islet infiltrates of female and male NOD mice at various ages. We found that the
      most significant difference in cytokine production between sexes was during the
      early stages of insulitis at 4 wk of age. IFN-gamma was significantly higher in
      young females, whereas IL-4 was higher in young males. CD4(+) T cells isolated
      from lymph nodes of female mice and activated with anti-CD3 and anti-CD28 Abs
      produced more IFN-gamma, but less IL-4, as compared with males. Treatment of
      CD4(+) T cells with estrogen significantly increased, whereas testosterone
      treatment decreased the IL-12-induced production of IFN-gamma. We then examined
      whether the change in IL-12-induced IFN-gamma production by treatment with sex
      hormones was due to the regulation of STAT4 activation. We found that estrogen
      treatment increased the phosphorylation of STAT4 in IL-12-stimulated T cells. We
      conclude that the increased susceptibility of female NOD mice to the development
      of autoimmune diabetes could be due to the enhancement of the Th1 immune response
      through the increase of IL-12-induced STAT4 activation by estrogen.

PMID- 11994497
TI  - Transforming growth factor beta signal transduction.
AB  - Transforming growth factor beta1 (TGF-beta1) is the prototypic member of a large
      family of structurally related pleiotropic-secreted cytokines that play a pivotal
      role in the control of differentiation, proliferation, and state of activation of
      many different cell types including immune cells. TGF-beta family members have
      potent immunosuppressor activities in vitro and in vivo. These cytokines trigger
      their biological effects by inducing the formation of a heteromeric transmembrane
      serine/threonine kinase receptor complex. These receptors then initiate
      intracellular signaling through activation of Smad proteins, and specific Smads
      become phosphorylated and associate with other Smads. These heteromeric Smad
      complexes accumulate in the nucleus, where they modulate the expression of target
      genes. Recent data support the notion that Smads are important intracellular
      effectors of TGF-beta in immune cells. Here, we review recent advances in TGF
      beta signal transduction in immune cells.

PMID- 11994498
TI  - Unlocking the secrets of galectins: a challenge at the frontier of glyco
      immunology.
AB  - Over the last decade, we have witnessed an explosion of information regarding the
      function of glycoconjugates, carbohydrate-binding proteins, and the elucidation
      of the sugar code. This progress has yielded not only important insights into
      fundamental areas of glycobiology but has also influenced other fields such as
      immunology and molecular medicine. A family of galactoside-binding proteins,
      called galectins, has emerged recently as a novel kind of bioactive molecules
      with powerful, immunoregulatory functions. Different members of this family have
      been shown to modulate positively or negatively multiple steps of the
      inflammatory response, such as cell-matrix interactions, cell trafficking, cell
      survival, cell-growth regulation, chemotaxis, and proinflammatory cytokine
      secretion. To introduce a comprehensive overview of these new advances, here we
      will explore the molecular mechanisms and biochemical pathways involved in these
      functions. We will also examine the role of these proteins in the modulation of
      different pathological processes, such as chronic inflammation, autoimmunity,
      infection, allergic reactions, and tumor spreading. Understanding the intimate
      mechanisms involved in galectin functions will help to delineate selective and
      novel strategies for disease intervention and diagnosis.

PMID- 11994499
TI  - The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine
      kinase signaling in the immune system.
AB  - The Cbl family of proteins are evolutionarily conserved negative regulators of
      activated tyrosine kinase-coupled receptors. Antigen receptors are prominent
      targets of negative regulation by the Cbl family members, Cbl and Cbl-b, which
      proteins function as ubiquitin ligases. Cbl and Cbl-b contain substrate
      recognition domains that interact specifically with activated protein tyrosine
      kinases of the Src and Syk/ZAP-70 families. Cbl-mediated ubiquitination of these
      kinases leads to their degradation, resulting in attenuation of receptor signals.
      Cbl may also control activation-induced monoubiquitination of antigen receptors,
      thus facilitating their delivery to lysosomes for subsequent degradation.
      Finally, the interactions of Cbl proteins with downstream targets of tyrosine
      kinases, such as PI-3-kinase and Vav, could provide an additional mechanism to
      attenuate receptor signaling. By targeting multiple components of antigen
      receptor signaling for degradation, the Cbl protein family provides a critical
      mechanism to ensure an appropriate immune response. The hyperresponsiveness of
      Cbl(-/-) and Cbl-b(-/-) lymphocytes and the autoimmune phenotype of Cbl-b(-/-)
      mice lend strong support for this proposal. The ability to control early receptor
      signals through regulated protein degradation provides a novel paradigm of
      immunoregulation.

PMID- 11994500
TI  - Adhesion to extracellular matrix proteins modulates bovine neutrophil responses
      to inflammatory mediators.
AB  - The neutrophil inflammatory response can be altered profoundly by contact with
      extracellular matrix proteins (ECMs). We characterized functional responses
      (intracellular calcium, actin polymerization, degranulation, adhesion, and
      oxidative burst) of bovine neutrophils adhered to selected ECM proteins [collagen
      IV, laminin, fibronectin, thrombospondin, and heparan sulfate proteoglycan (HSP)]
      in response to interleukin-8 (IL-8) and platelet-activating factor (PAF).
      Neutrophil adhesion to ECMs altered responses to PAF and IL-8, although some
      functions were more responsive to modulation. The most susceptible function was
      reactive oxygen species (ROS) production. ROS production in response to PMA and
      TNF-alpha was supported differentially by various ECMs, and PAF and IL-8
      "priming" had strikingly different effects, depending on the ECM present.
      Although PAF and IL-8 inhibited TNF-alpha-induced ROS production in neutrophils
      adhered to collagen, fibronectin, and laminin, PAF enhanced ROS production
      strongly in HSP-adherent cells. This study illustrates how neutrophils can
      integrate multiple stimuli, resulting in complex modulation of their functional
      response.

PMID- 11994501
TI  - Oxidant-mediated phosphatidylserine exposure and macrophage uptake of activated
      neutrophils: possible impairment in chronic granulomatous disease.
AB  - The removal of neutrophils from inflammatory sites is essential for the
      resolution of inflammation. Surface changes, including phosphatidylserine
      exposure, label neutrophils for phagocytosis by macrophages. Here, we demonstrate
      that externalization of phosphatidylserine and uptake by monocyte-derived
      macrophages occurred in human neutrophils ingesting Staphylococcus aureus. Both
      processes were dependent on oxidant production from the neutrophil NADPH oxidase.
      There was no requirement for myeloperoxidase, and H(2)O(2) was identified as the
      most likely trigger for PS exposure. We hypothesize that clearance of stimulated
      neutrophils would be delayed in chronic granulomatous disease (CGD) neutrophils,
      which lack a functional NADPH oxidase. To explore this possibility, heat-killed
      S. aureus were injected into the peritoneum of CGD and normal mice. Elevated
      neutrophil numbers were observed in the inflammatory exudate of the CGD animals,
      consistent with impaired recognition and clearance.

PMID- 11994502
TI  - The immunosuppressive effects of chronic morphine treatment are partially
      dependent on corticosterone and mediated by the mu-opioid receptor.
AB  - Wild-type and mu-opioid receptor knockout (MORKO) mice were used to investigate
      the role of corticosterone (CORT) and the mu-opioid receptor (MOR) in chronic
      morphine-mediated immunosuppression. We found that although plasma CORT
      concentrations in CORT infusion (10 mg/kg/day) and morphine-pellet implantation
      (75 mg) mice were similar (400-450 ng/ml), chronic morphine treatment resulted in
      a significantly higher (two- to threefold) inhibition of thymic, splenic, and
      lymph node cellularity; inhibition of thymic-lymphocyte proliferation; inhibition
      of IL-2 synthesis; and activation of macrophage nitric oxide (NO) production when
      compared with CORT infusion. In addition, results show that the inhibition of IFN
      gamma synthesis and splenic- and lymph node-lymphocyte proliferation and
      activation of macrophage TNF-alpha and IL-1beta synthesis occurred only with
      chronic morphine treatment but not with CORT infusion. These morphine effects
      were abolished in MORKO mice. The role of the sympathetic nervous system on
      morphine-mediated effects was investigated by using the ganglionic blocker
      chlorisondamine. Our results show that chlorisondamine was able to only partially
      reverse morphine's inhibitory effects. The results clearly show that morphine
      induced immunosuppression is mediated by the MOR and that although some functions
      are amplified in the presence of CORT or sympathetic activation, the inhibition
      of IFN-gamma synthesis and activation of macrophage-cytokine synthesis is CORT
      independent and only partially dependent on sympathetic activation.

PMID- 11994503
TI  - Activation-induced expression of MICA on T lymphocytes involves engagement of CD3
      and CD28.
AB  - MICA is an HLA-related cell stress-regulated antigen recognized by cytotoxic
      cells expressing the NKG2D molecule. Although resting lymphocytes do not express
      MICA, it can be induced on PHA-activated T cells. Here, we demonstrate by Western
      blot that MICA is induced on allogeneic-activated CD4(+) and CD8(+) T
      lymphocytes. Blocking activation with anti-HLA class I, anti-HLA-DR, or anti-CD86
      mAb affected the expression of MICA slightly. When T cells were stimulated with
      anti-CD3 or anti-CD28 mAb plus PMA, a sustained up-regulation of MICA was
      observed by Western blot, RT-PCR, and flow cytometry. The expression of MICA
      reached a plateau at day 4 after CD3 engagement and at day 3 after anti-CD28/PMA
      stimulation. Conversely, the proliferative response reached a peak at day 4.
      Hence, CD3 or CD28 engagement induces MICA expression on T lymphocytes. This
      activation-induced expression might participate in NKG2D-mediated cytotoxicity
      toward activated T cells to maintain homeostasis during an ongoing immune
      response.

PMID- 11994504
TI  - Different G(i)-coupled chemoattractant receptors signal qualitatively different
      functions in human neutrophils.
AB  - fMLP- or TNF-alpha-stimulated neutrophils produced H(2)O(2) when they adhered to
      fibrinogen-coated surfaces but not when they adhered to collagen I-, collagen IV
      , or Matrigel-coated surfaces. In contrast, LTB4- or IL-8-stimulated neutrophils
      did not produce H(2)O(2) when they adhered to any of these surfaces. fMLP and TNF
      alpha were much more potent than LTB4 and IL-8 in stimulating neutrophils to up
      regulate and to activate their alpha(M)beta(2) integrins, as measured by the
      binding of specific monoclonal antibodies. Pretreatment of neutrophils with
      pertussis toxin completely blocked their production of H(2)O(2) on fibrinogen
      coated surfaces in response to fMLP and their migration through Matrigel in
      response to fMLP, LTB4, and IL-8. These data show that although the fMLP, LTB4,
      and IL-8 receptors are coupled to pertussis toxin-sensitive Galpha proteins, they
      signal neutrophils to initiate qualitatively different effector functions. We
      propose that the qualitative differences in effector functions signaled by
      different chemoattractants reflect qualitative differences in using G-protein
      beta and/or gamma subunits or other factors by their cognate receptors.

PMID- 11994505
TI  - Nitric oxide activates ATP-dependent K+ channels in human eosinophils.
AB  - Nitric oxide (NO) affects the function of ion channels in many cell types, but
      its role in the regulation of eosinophil ion channels is unknown. In this study,
      we used the perforated patch-clamp method to investigate the effect of endogenous
      and exogenous NO on eosinophil ion channels. Using the NO synthase inhibitor, N
      nitro-L-arginine methyl ester, we showed that endogenous NO did not affect the
      whole-cell current in eosinophil. However, two NO donors, S-nitroso-glutathione
      and S-nitroso-N-acetyl penicillamine, activated whole-cell currents via a NO/cGMP
      dependent pathway. Ion substitution and pharmacological studies showed that NO
      activated currents were carried by K+ ions, likely through ATP-dependent K+
      channels (K(ATP)). Although RT-PCR studies showed the expression of several
      classes of K+ channels in human eosinophils, NO donors affected only K(ATP)
      channel function. We conclude that NO, at concentrations likely to be encountered
      in vivo, could prevent eosinophil activation by opening K(ATP) channels.

PMID- 11994506
TI  - Differential and competitive activation of human immune cells by distinct classes
      of CpG oligodeoxynucleotide.
AB  - Synthetic oligodeoxynucleotides (ODN) expressing "CpG motifs" show promise as
      immune adjuvants, antiallergens, anticancer, and immunoprotective agents. Two
      structurally distinct classes of CpG ODN have been identified that stimulate
      human PBMC. This work establishes that both types of ODN bind to and are
      internalized by the same individual B cells, NK cells, and monocytes. However,
      the intracellular localization of "D" and "K" ODN differs, as does their
      functional activity: "K" type ODN trigger monocytes and B cells to proliferate
      and secrete IL-6 and IgM, whereas "D" type ODN induce NK cells to produce IFN
      gamma and monocytes to differentiate into CD83(+)/CD86(+) dendritic cells. In
      monocytes, these two types of ODN (which differ in backbone composition and CpG
      motif) cross-inhibit one another's activity. Thus, different types of CpG ODN
      have distinct and in some cases incompatible effects on the same cells, a finding
      with important implications for the therapeutic use of these agents.

PMID- 11994507
TI  - Neutrophils from MMP-9- or neutrophil elastase-deficient mice show no defect in
      transendothelial migration under flow in vitro.
AB  - Recent evidence has suggested a role for neutrophil proteases during certain
      inflammatory responses. We demonstrated previously that neutrophil proteases can
      degrade components of the adherens junctions during neutrophil-endothelial
      adhesion. We tested the hypothesis that degradation of VE-cadherin at lateral
      junctions by elastase or MMP-9 facilitates neutrophil transendothelial migration.
      Neutrophils from MMP-9 or elastase null mice and strain-matched control mice
      expressed high levels of LFA-1, Mac-1, and L-selectin on their cell surface.
      Under flow conditions, wild-type and deficient neutrophils rolled, arrested, and
      transmigrated activated murine endothelium. There was no difference in the total
      numbers of interacting neutrophils or in the percentage of transmigrated cells.
      In addition, deficient neutrophils remained capable of degrading murine
      endothelial VE-cadherin. These results indicate that although neutrophil
      proteases may play a role in the acute inflammatory response, neutrophil elastase
      or MMP-9 is not essential for neutrophil transendothelial migration in this
      murine system.

PMID- 11994508
TI  - Endothelins regulate mediator production of rat tissue-cultured mucosal mast
      cells. Up-regulation of Th1 and inhibition of Th2 cytokines.
AB  - Mast cells have been shown to produce endothelin-1 (ET-1) and to express ET
      receptors. Thus, we postulated that ETs modulate mast cell mediator production in
      an autocrine manner. Rat tissue-cultured mast cells (RCMC-1) were incubated with
      exogenous ET-1 or ET-3, and beta-hexosaminidase release and TNF, IL-4, IL-10, IL
      12, IL-13, macrophage inflammatory protein-1alpha (MIP-1alpha), and nitric oxide
      (NO) production were investigated. ET-1 and -3 induced the release of beta
      hexosaminidase and TNF and of mRNA expression. An antagonist of the ET(B)
      receptor subtype abrogated ET-stimulated TNF release, although ET(A) and ET(B)
      receptors have been identified by immunocytochemistry. It is interesting that ET
      1 and ET-3 inhibited (25-30%) mRNA expression of Th2-type cytokines (IL-4, IL-10,
      and IL-13) and increased IL-12 release (39% and 41%, respectively) without
      affecting MIP-1alpha and NO production. Thus, our data suggest that ETs may play
      an important role in modulating the cytokine network by regulating Th1/Th2
      cytokine production by mast cells.

PMID- 11994509
TI  - Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from
      Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent
      on MCP-1 production by IFN-gamma-primed-macrophages.
AB  - Glycosylphosphatidylinositol-anchored mucin-like glycoproteins from Trypanosoma
      cruzi trypomastigotes (tGPI-mucins) activate macrophages in vitro to produce
      proinflammatory cytokines, chemokines, and nitric oxide. These effects of tGPI
      mucins may be important in the ensuing immune response to T. cruzi. Here, we have
      sought evidence for a role of tGPI-mucins in mediating leukocyte recruitment in
      vivo. tGPI-mucins are highly effective in promoting cell recruitment in the
      pleural cavity of mice primed with IFN-gamma-inducing agents but not in naive
      mice. Maximal recruitment was observed at a dose between 250 and 1250 ng tGPI
      mucins. There was a significant elevation in the levels of MCP-1 in the pleural
      cavity of primed animals injected with tGPI-mucins, and in vivo neutralization of
      MCP-1 abolished leukocyte recruitment. Pretreatment with anti-MIP-1alpha or anti
      RANTES had no effect on the recruitment induced by tGPI-mucins. MCP-1
      immunoreactivity was detected in pleural macrophages, and macrophages produced
      MCP-1 in vitro, especially after priming with IFN-gamma. Finally, tGPI-mucins
      induced significant leukocyte recruitment in primed C3H/HeJ but not in TLR2
      deficient mice. Together, our results suggest that T. cruzi-derived GPI-mucins in
      conjunction with IFN-gamma may drive tissue chemokine production and inflammation
      and bear a significant role in the pathogenesis of Chagas disease.

PMID- 11994510
TI  - Antagonistic effects of IL-4 and TGF-beta1 on Langerhans cell-related antigen
      expression by human monocytes.
AB  - In this study, we analyzed the specific effects of transforming growth factor
      beta (TGF-beta1) and/or IL-4 on monocyte-derived cells. Monocytes were cultured
      with GM-CSF, GM-CSF/TGF-beta1, GM-CSF/IL-4, or GM-CSF/IL-4/TGF-beta1 before cell
      morphology, phenotype, and function were assessed. As expected, interleukin-4 is
      mandatory for monocyte differentiation into potent allostimulatory DC. In its
      absence, monocyte-derived cells share many phenotypic and functional features
      with macrophages. However, it is interesting that the cells express E-cadherin,
      independent of exogenous TGF-beta1, and addition of the cytokine induced CCR6
      expression. Most importantly, a subset of monocytes cultured with GM-CSF/TGF
      beta1 expresses Langerin, as confirmed by electron microscopy analysis. Langerin
      engagement with specific monoclonal antibodies induces its internalization and
      the formation of typical Birbeck granules. Monocytes cultured in GM-CSF/IL-4 did
      not express the LC markers E-cadherin, CCR6, or Langerin. The simultaneous
      addition of TGF-beta1 allows most of the cells to express E-cadherin but rarely
      CCR6 and Langerin. Taken together, the results add further evidence that LC can
      derive from monocytes and demonstrate an antagonistic effect of IL-4 and TGF
      beta1 on monocyte differentiation toward the LC pathway.

PMID- 11994511
TI  - The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed on
      myeloid cells.
AB  - The EGF-TM7 family is a group of class B seven-span transmembrane (TM7) receptors
      expressed predominantly by cells of the immune system. Family members CD97, EMR1,
      EMR2, EMR3, and ETL are characterized by an extended extracellular region with a
      variable number of N-terminal epidermal growth factor (EGF)-like domains coupled
      to a TM7 domain by a stalk. The EGF domain region of the recently identified EMR2
      differs from that of CD97 in only 6 out of 236 amino acids. Although small, this
      difference has been shown to alter ligand specificity. To analyze the structure
      and cellular distribution of EMR2, a specific monoclonal antibody (2A1) was
      generated. Use of 2A1 has demonstrated EMR2, like CD97, to be expressed as a
      heterodimeric receptor consisting of an extracellular alpha part and a
      TM7/cytoplasmic beta part. Analysis of EMR2 expression on primary blood
      leukocytes, on hematopoietic cells lines, and in situ revealed a myeloid
      restricted profile. Highest expression levels were detected on the more mature
      CD16(+) blood monocytes, on macrophages, and on BDCA-3(+) myeloid DC, whereas
      little if any expression was found on granulocytes. Unlike CD97, no expression
      was observed on resting or activated lymphocytes. Different expression patterns
      and the inability of EMR2 to interact with the CD97 ligand CD55 indicate that the
      molecular twins EMR2 and CD97 likely have nonredundant functions.

PMID- 11994512
TI  - Fas activation opposes PMA-stimulated changes in the localization of PKCdelta: a
      mechanism for reducing neutrophil adhesion to endothelial cells.
AB  - We have shown previously that Fas activation results in a partial reduction of
      phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophil adhesion to
      endothelial cells. The reduction in adhesion precedes early membrane markers of
      apoptosis and is not associated with any loss of membrane integrity. Rather, Fas
      activation reduces the PMA-stimulated expression and aggregation of beta2
      integrins responsible for endothelial adhesion. A possible signaling mechanism
      for Fas effects on adhesion is the localization of protein kinase C delta
      (PKCdelta). Western blot and immunofluorescence studies indicated that 1 h of Fas
      activation is required to reduce PMA-stimulated translocation of PKCdelta to the
      membrane and adhesion. Rottlerin, a PKCdelta inhibitor, also reduced PMA-induced
      PKCdelta translocation and adhesion. In contrast, Go6976, an inhibitor of
      conventional PKC isotypes, did not affect PMA-stimulated PKCdelta translocation
      or reduce adhesion. There was no additive effect of Fas activation and rottlerin
      on reducing adhesion, suggesting that both agents were using a common pathway.

PMID- 11994513
TI  - The expression pattern of the ITIM-bearing lectin CLECSF6 in neutrophils suggests
      a key role in the control of inflammation.
AB  - In our study of the modulation of the expression of inflammation-related genes in
      neutrophils, we have found a gene called CLECSF6 (C-type lectin superfamily 6).
      CLECSF6 expresses two mRNA species at low levels in resting neutrophils. Here, we
      describe for the first time the sequence of the short mRNA version. It lacks
      amino acids that are likely to affect the functionality of its protein product.
      GM-CSF, IL-3, IL-4, and IL-13 caused an accumulation of the short CLECSF6 mRNA in
      neutrophils. The surface expression of the CLECSF6 protein was reduced by TNF
      alpha, IL-1alpha, LPS, and Matrigel. CLECSF6 bears the immunoreceptor tyrosine
      based inhibition motif (ITIM) involved in signal transduction resulting in the
      inhibition of leukocyte activation. We propose that some neutrophil activators
      modulate the expression of CLECSF6 at the mRNA (GM-CSF, IL-3, IL-4, and IL-13) or
      protein (TNF-alpha, IL-1alpha, LPS, and Matrigel) levels in ways that block ITIM
      based transduction of anti-inflammatory signals and therefore promote
      inflammation.

PMID- 11994514
TI  - Recognition and phagocytosis of apoptotic T cells by resident murine tissue
      macrophages require multiple signal transduction events.
AB  - Macrophages (Mo) ingest apoptotic cells with unique effects on their cytokine
      production, but the signaling pathways involved are virtually unknown. Signal
      transduction in response to recognition of apoptotic thymocytes by resident
      murine alveolar (AMo) or peritoneal (PMo) Mo was studied by in vitro phagocytosis
      assay. Phagocytosis was decreased in a dose-dependent and nontoxic manner by
      inhibiting phosphatidylinositol 3 kinase (wortmannin and LY294002), protein
      tyrosine phosphorylation (herbimycin A, genistein, piceatannol, and for AMo only,
      PP2), and protein kinase C (staurosporine, Go 6976, and calphostin C). Exposure
      of Mo to apoptotic or heat-killed thymocytes, but not to viable thymocytes,
      activated ERK1/2 rapidly, as detected by specific phosphorylation, but did not
      activate NF-kappaB or MAP kinases p38 or JNK. Mo phagocytosis of apoptotic T
      cells requires tyrosine, serine/threonine, and lipid phosphorylation. Mo
      recognition of apoptotic T cells triggers rapid but limited MAP kinase
      activation.

PMID- 11994515
TI  - Regulation of NRAMP1 gene expression by 1alpha,25-dihydroxy-vitamin D(3) in HL-60
      phagocytes.
AB  - The natural resistance-associated macrophage protein 1 (Nramp1) is a proton
      dependent transporter of divalent metals. We studied NRAMP1 expression during HL
      60 differentiation induced by VD and VD agonists. NRAMP1 and CD14 gene expression
      differed in kinetics of induction, mRNA levels and stability, and response to VD
      combined with PMA, whereas a combination of VD and IFN-gamma induced similar up
      regulation. NRAMP1 protein expression paralleled the accumulation of mRNA and was
      localized in the phagosomal membrane after phagocytosis. A promoter construct
      extending 647 bp upstream of NRAMP1 ATG showed myeloid-specific transcription in
      transient transfection assays, which was up-regulated by VD in HL-60. In HL-60
      clones stably transfected with this construct, transcription was apparently
      induced through indirect VD genomic effects, and there was accordance between the
      levels of reporter transcription and endogenous NRAMP1 mRNA in response to VD but
      not to IFN-gamma. Thus, VD genomic effects stimulate NRAMP1 transcription and
      protein expression in maturing phagocytes.

PMID- 11994517
TI  - Evaluation of delayed appearance of acetazolamide effect in patients with chronic
      cerebrovascular ischemic disease: feasibility and usefulness of SPECT method
      using triple injection of ECD.
AB  - The purpose of this study was to verify the feasibility and usefulness of a new
      SPECT method, called triple injection of (99m)Tc-ethylcysteinate dimer (TIE), in
      evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in
      patients with chronic cerebral ischemic disease. METHODS: Three equal-volume
      splits of (99m)Tc-ethylcysteinate dimer were intravenously administered, and
      1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in
      the lateral ventricle was used as a region of interest. The data at rest and at
      7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were
      obtained by dynamic SPECT, and a time response curve to ACZ was obtained through
      the relative ratio of regional counts to the data at rest, not through regional
      cerebral blood flow. Nine cases of complete occlusion of the internal carotid
      artery (IC) and 6 cases of severe IC stenosis were analyzed. RESULTS: In 12
      healthy volunteers (24 cerebral hemispheres) using a placebo (negative control),
      the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ
      20, respectively) were 100%, 100.4% +/- 2.8%, and 99.6% +/- 3.6%, respectively,
      indicating the accuracy of the TIE method. In a positive control using 24 normal
      cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% +/- 8.0%)
      was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% +/- 12.8%).
      The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients
      with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal
      response at ACZ 20 (delayed response). Furthermore, in patients with severe IC
      stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy
      was confirmed not only at ACZ 20 but also at ACZ 7.5. CONCLUSION: The TIE method
      using SPECT may be a potentially useful and sensitive strategy in clinical
      evaluation of the delayed or poor appearance of ACZ effects in patients with
      chronic cerebrovascular ischemic disease.

PMID- 11994518
TI  - Kidney allografts and remaining contralateral donor kidneys before and after
      transplantation: assessment by quantitative (99m)Tc-DMSA SPECT.
AB  - We used (99m)Tc-dimercaptosuccinic acid (DMSA) quantitative SPECT (QDMSA) to
      assess the function of kidneys before harvesting and after transplantation as
      well as the function of remaining donor kidneys. METHODS: Nineteen kidney donors
      underwent a baseline QDMSA study before nephrectomy. The allografts of these
      kidneys were studied in recipients at 1 wk, 1-2 mo, and 6-15 mo after
      transplantation. The kidneys remaining in 16 donors were studied at 1-2 mo and 6
      15 mo after harvesting. The parameters obtained in each SPECT study included
      functional volume, concentration of (99m)Tc-DMSA per cubic centimeter of renal
      tissue, and total kidney uptake. Clinical evaluation and determination of serum
      creatinine levels took place at the same time as SPECT. RESULTS: On the basis of
      the clinical evaluation, 14 grafts had normal function and 5 were impaired. The
      mean +/- SD of kidney uptake values expressed as percentage of baseline values
      were 131% +/- 30% in normal grafts versus 57% +/- 5% in impaired grafts at 1 wk
      (P < 0.01), 173% +/- 57% versus 65% +/- 10% at 1-2 mo (P < 0.001), and 190% +/-
      50% versus 69% +/- 14% at 6-15 mo after transplantation (P < 0.01). Uptake values
      in the donors' remaining kidneys were 159% +/- 27% of baseline values at 1-2 mo
      and 164% +/- 30% at 6-15 mo after nephrectomy. Allografts and remaining kidneys
      showed a similar increase in total kidney uptake as a result of an increase in
      both functional volume and concentration. CONCLUSION: QDMSA may be a noninvasive
      assessment tool in kidney transplantation from living donors.

PMID- 11994519
TI  - Electrocardiographic gated (99m)Tc-MIBI SPECT for functional assessment of
      patients after coronary artery bypass surgery: comparison of wall thickening and
      wall motion analysis.
AB  - Abnormal septal motion after coronary artery bypass graft surgery (CABG) is a
      common finding. This study was undertaken to investigate the change in various
      global and regional ventricular function parameters measured by gated myocardial
      perfusion SPECT after surgery and to determine which quantitative parameter of WT
      and WM is more appropriate for the evaluation of regional cardiac function,
      especially in the septum of patients with CABG. METHODS: Before and 3 to 5 wk
      after CABG (all patients underwent at least 1 bypass grafting to the left
      anterior descending coronary artery), 35 patients (28 men, 7 women) underwent
      gated SPECT using (99m)Tc-methoxyisobutylisonitrile. Quantitative global and
      regional ventricular functional analysis was performed using quantitative gated
      SPECT software. RESULTS: Global ejection fraction did not change (59.3% +/- 16.0%
      to 60.5% +/- 14.5%, P = 0.24). However, end-diastolic and end-systolic volumes
      lessened significantly after CABG (81.4 +/- 37.3 mL to 68.9 +/- 28.9 mL, P <
      0.0001, and 38.1 +/- 33.1 mL to 30.4 +/- 23.0 mL, P < 0.005, respectively). As
      global function parameters, the changes in both total WM (r = 0.88) and WT (r =
      0.86) correlated well with the change in ejection fraction after surgery.
      Segmental analysis showed a significant postoperative increase in relative tracer
      uptake in the anterior, anteroseptal, inferoseptal, and inferior walls and in the
      apex. Segmental wall motion (WM) deteriorated in the anteroseptal, inferoseptal,
      and mid anterior walls. On the other hand, anterolateral, inferolateral, and
      inferior WM increased. As a whole, these WM changes showed a reduction in septal
      motion associated with a concomitant increase in lateral motion after surgery.
      Segmental wall thickening, however, did not decrease in septal areas and did not
      increase in the lateral wall and correlated with percentage tracer uptake (r =
      0.69) better than WM did (r = 0.30) after CABG. CONCLUSION: In patients with
      CABG, postoperative WM analysis by gated SPECT underestimated septal motion and
      overestimated lateral motion because of exaggerated systolic anteromedial cardiac
      translation. Therefore, wall thickening analysis would be recommended for the
      evaluation of postoperative cardiac function.

PMID- 11994520
TI  - Potential of (99m)Tc-MIBI for detecting bone marrow metastases.
AB  - In this study, we evaluated the potential of (99m)Tc-hexakis-2
      methoxyisobutylisonitrile (MIBI) for detecting bone metastases in comparison with
      a conventional bone tracer. METHODS: (99m)Tc-MIBI and (99m)Tc-hydroxymethylene
      diphosphonate (HMDP) scans were obtained from 99 patients with proven malignant
      diseases and suspected bone metastases. We compared 373 lesions that showed
      abnormal uptake on (99m)Tc-MIBI scans or (99m)Tc-HMDP scans (or both). RESULTS:
      Bone metastases were confirmed in 334 of 373 lesions. Thirty-nine lesions on
      (99m)Tc-HMDP scans had false-positive findings, but only 2 of these lesions had
      false-positive findings on (99m)Tc-MIBI scans. (99m)Tc-MIBI and (99m)Tc-HMDP
      scans were equivalent in 168 of 334 lesions (50.3%). (99m)Tc-MIBI scans correctly
      detected more lesions than (99m)Tc-HMDP scans: 284 lesions (85.0%) versus 218
      lesions (65.3%) (P < 0.005), respectively. (99m)Tc-MIBI scans showed a markedly
      higher sensitivity for detecting metastases in the femur and humerus compared
      with (99m)Tc-HMDP scans: 97 of 98 lesions (99.0%) versus 35 of 98 lesions (35.7%)
      (P < 0.005) and 21 of 22 lesions (95.5%) versus 11 of 22 lesions (50.0%) (P <
      0.005), respectively. (99m)Tc-HMDP scans of 17 patients showed no abnormal
      images. However, (99m)Tc-MIBI scans correctly detected bone metastases, and
      subsequent development of multiple lesions was observed on follow-up (99m)Tc-HMDP
      scans of 15 patients. (99m)Tc-MIBI scans were superior to (99m)Tc-HMDP scans in
      the detection of metastases attributed to breast cancer, multiple myeloma, and
      hepatoma. On the contrary, (99m)Tc-MIBI scans were less sensitive than (99m)Tc
      HMDP scans for detecting bone metastases attributed to prostate cancer in the
      other skeletal sites except for femur and humerus. CONCLUSION: (99m)Tc-MIBI scans
      have better sensitivity for detecting bone metastases and provide more specific
      complementary findings than conventional bone scans. (99m)Tc-MIBI accumulation
      attributed to bone marrow metastases may occur at an early stage, before the bone
      remodeling process in the surrounding bone can be detected on conventional bone
      scans.

PMID- 11994521
TI  - Role of (18)F-FDG dual-head gamma-camera coincidence imaging in recurrent or
      metastatic colorectal carcinoma.
AB  - (18)F-FDG PET has been shown to be of high diagnostic accuracy for the evaluation
      of recurrent colorectal cancer. However, the limited availability of PET scanners
      precludes (18)F-FDG assessment of many patients for whom the study is indicated.
      An alternative is the SPECT system in coincidence mode. The aim of this study was
      to determine the role of dual-head camera (18)F-FDG coincidence imaging (DHC
      (18)F-FDG) in patients with recurrent colorectal cancer. METHODS: Sixty-seven DHC
      (18)F-FDG studies were performed on 62 patients with suspected recurrent
      colorectal cancer. Reports of contemporary CT were available for the purpose of
      correlation for 61 of the studies. The final diagnosis of the imaging findings
      was based on histology or clinical and imaging follow-up of at least 6 mo.
      RESULTS: In lesion-based analysis, 103 tumor sites were suspected on DHC (18)F
      FDG, CT, or colonoscopy. Ninety-three of them were found to be true tumor sites.
      For DHC (18)F-FDG, the sensitivity was 88%, specificity was 80%, positive
      predictive value (PPV) was 98%, negative predictive value (NPV) was 42%, and
      accuracy was 87%. For CT, the sensitivity was 63%, specificity was 10%, PPV was
      85%, NPV was 3%, and accuracy was 57%. In patient-based analysis, DHC (18)F-FDG
      differentiated patients with recurrent cancer from disease-free patients with a
      sensitivity of 91%, specificity of 73%, PPV of 94%, NPV of 62%, and accuracy of
      88%. DHC (18)F-FDG detected tumor sites in 12 (67%) of 18 patients with elevated
      carcinoembryonic antigen and negative CT findings. CONCLUSION: DHC (18)F-FDG is
      an adequate readily available technique for assessment of recurrent colorectal
      cancer and has a diagnostic accuracy better than that of CT.

PMID- 11994522
TI  - Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y
      DOTATOC.
AB  - The aim of this prospective phase II study was to evaluate the tumor response of
      neuroendocrine tumors to high-dose targeted irradiation with 7.4 GBq/m(2) of the
      radiolabeled somatostatin analog (90)Y-1,4,7,10-tetra-azacyclododecan-4,7,10
      tricarboxy-methyl-1-yl-acetyl-D-Phe-Tyr(3)-octreotide (DOTATOC). In addition, we
      investigated the clinical benefit of (90)Y-DOTATOC regarding the malignant
      carcinoid syndrome and tumor-associated pain. METHODS: Thirty-nine patients (mean
      age, 55 y) with progressive neuroendocrine gastroenteropancreatic and bronchial
      tumors were included. The treatment consisted of 4 equal intravenous injections
      of a total of 7.4 GBq/m(2) (90)Y-DOTATOC, administered at intervals of 6 wk.
      After each treatment cycle, a standardized clinical benefit assessment using the
      National Cancer Institute grading criteria (NCI-CTC) was performed. RESULTS: The
      objective response rate according to World Health Organization (WHO) criteria was
      23%. For endocrine pancreatic tumors (13 patients), the objective response rate
      was 38%. Complete remissions were found in 5% (2/39), partial remissions in 18%
      (7/39), stable disease in 69% (27/39), and progressive disease in 8% (3/39). A
      significant reduction of clinical symptoms could be found in 83% of patients with
      diarrhea, in 46% of patients with flush, in 63% of patients with wheezing, and in
      75% of patients with pellagra. The overall clinical benefit was 63%. All
      responses (both clinical benefit and WHO response) were ongoing for the duration
      of follow-up (median, 6 mo; range, 2-12 mo). Side effects were grade 3 or 4 (NCI
      CTC) lymphocytopenia in 23%, grade 3 anemia in 3%, and grade 2 renal
      insufficiency in 3%. CONCLUSION: High-dose targeted radiotherapy with 7.4
      GBq/m(2) (90)Y-DOTATOC is a well-tolerated treatment for neuroendocrine tumors,
      with remarkable clinical benefit and objective response.

PMID- 11994523
TI  - New advances in peptide receptor radionuclide therapy.

PMID- 11994524
TI  - Reverse redistribution on exercise-redistribution (201)Tl SPECT in chronic
      ischemic dysfunction: predictive of functional outcome after revascularization?
AB  - This study analyzed the incidence and clinical significance of reverse
      redistribution (RR) on stress-redistribution (201)Tl SPECT studies in patients
      with poor left ventricular function and tested the hypothesis that the RR
      phenomenon could be caused by artifacts. METHODS: Seventy-three consecutive
      patients with chronic coronary artery disease and left ventricular dysfunction
      (ejection fraction, 36% +/- 12%) who underwent exercise-redistribution
      reinjection (201)Tl SPECT before myocardial revascularization were included.
      Recovery of left ventricular systolic function was assessed with 2-dimensional
      echocardiography performed before and 5.5 +/- 2.5 mo after revascularization. RR
      was determined visually and confirmed quantitatively as a > or = 10% decrease in
      (201)Tl uptake on the circumferential profiles. The left ventricle was divided in
      16 segments for (201)Tl uptake and wall motion analyses. RESULTS: RR was present
      in 39 of 1,168 segments (3.3%) and in 18 of 73 patients (25%). Before
      revascularization, regional wall motion was normal in 26 of 39 RR segments (67%),
      hypokinetic in 7 of 39 (18%), and akinetic in 6 of 39 (15%). Eight percent of all
      dysfunctional segments (13/167) of RR patients presented RR. After
      revascularization, 60 of 167 dysfunctional segments (36%) improved function by >
      or = 1 grade, among which 8 (13%) displayed RR on (201)Tl SPECT before
      revascularization. Segments with RR improved function more frequently than those
      without RR (62% vs. 34%; P = 0.05). Using a threshold for segmental (201)Tl
      uptake of >54%, the accuracy of (201)Tl reinjection to detect functional
      improvement in RR segments after revascularization was 77% (10/13). Artifactually
      induced RR was also excluded in all but 1 case because no increased activity of
      the pixel used for normalization could be found on redistribution images relative
      to that of the stress images. CONCLUSION: These data suggest that in patients
      with chronic left ventricular ischemic dysfunction, RR on exercise-redistribution
      (201)Tl SPECT is not an artifact and occurs rarely in normally functioning and in
      dysfunctional myocardium. In the latter, RR is frequently associated with
      myocardial viability as shown by functional recovery after revascularization.
      However, the presence or absence of RR in dysfunctional segments seems to be of
      little clinical relevance.

PMID- 11994525
TI  - The continuing story of (201)Tl reverse redistribution: reverse redistribution is
      still alive, but is the myocardium still viable?

PMID- 11994526
TI  - Comparison of (123)I and (131)I for whole-body imaging in thyroid cancer.
AB  - We compared the diagnostic sensitivities of (123)I and (131)I whole-body imaging
      in differentiated thyroid cancer. METHODS: Twelve thyroidectomized patients (3
      previously treated with (131)I) were studied. After a period of thyroid hormone
      withdrawal, whole-body imaging was performed approximately 24 and 72-96 h after
      administration of 74-185 MBq (2-5 mCi) (123)I and 111-185 MBq (3-5 mCi) (131)I,
      respectively. RESULTS: Both (123)I and (131)I revealed residual thyroid tissue,
      present in 9 patients. (131)I detected metastases in 5 studies of 4 patients. In
      4 of 5 studies, (123)I missed metastases shown by (131)I in 8 body regions
      including the neck, mediastinum, lungs, and bone and detected 3 other sites of
      metastasis only in retrospect. No lesion was better seen with (123)I than with
      (131)I. CONCLUSION: Although (123)I is adequate for imaging residual thyroid
      tissue, it appears to be less sensitive than (131)I for imaging thyroid cancer
      metastases.

PMID- 11994527
TI  - Multicenter comparison of calibration and cross calibration of PET scanners.
AB  - The purpose of this study was to compare the calibration of PET scanners and
      their cross calibration to peripheral devices in a multicenter study. METHODS:
      Twenty-three dedicated PET scanners were investigated, applying standardized
      protocols. To ensure exact determination of the activity used, dose calibrators
      were checked using (68)Ge standards. RESULTS: Nine of 19 and 11 of 20 scanners
      displayed an error of <5% in 3-dimensional and 2-dimensional acquisition modes,
      respectively. Four and 5 scanners displayed an error of 10% in 3-dimensional and
      2-dimensional modes, respectively. All other scanners yielded errors of 5% to
      <10%. Because of hardware and software problems, the measurements performed on 1
      scanner could not be adequately analyzed. CONCLUSION: An investigation of
      calibration is mandatory. Especially for quantitative analyses in clinical
      multicenter trials, identification of potentially miscalibrated scanners is
      necessary.

PMID- 11994528
TI  - Lung ventilation/perfusion SPECT in the artificially embolized pig.
AB  - Planar lung scintigraphy is a standard method used for the diagnosis of lung
      embolism, but it is hampered by the high incidence of nondiagnostic tests.
      Ventilation/perfusion SPECT may possibly improve this situation. The objective of
      this study was to compare planar lung scintigraphy with ventilation/perfusion
      SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl.
      METHODS: Sixteen anesthetized pigs were each injected with zero to 4 latex
      emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli
      were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc
      diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar
      scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc
      and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled
      macroaggregated albumin were injected intravenously followed by SPECT and,
      finally, planar scintigraphy. The ventilation background was subtracted from the
      perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P)
      quotient image set. RESULTS: The cylindric emboli caused artifacts in the
      ventilation images; therefore, these were excluded from the final analysis.
      However, for the planar perfusion images of these pigs, sensitivity and
      specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both.
      For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and
      specificity were 64% and 79%, respectively, for the planar modality, whereas
      SPECT yielded values of 91% and 87%, respectively. CONCLUSION: V/P SPECT may
      improve the diagnostic power of lung scintigraphy.

PMID- 11994529
TI  - Lung ventilation/perfusion SPECT: the right technique for hard times.

PMID- 11994530
TI  - Dissociation between respiratory burst activity and deoxyglucose uptake in human
      neutrophil granulocytes: implications for interpretation of (18)F-FDG PET images.
AB  - Neutrophil granulocytes play a key role in the pathogenesis of a wide variety of
      pulmonary diseases. In many such conditions, the injury observed reflects the
      activation status rather than the total number of inflammatory cells present. The
      metabolic activity of neutrophils can now be assessed noninvasively using PET to
      measure the regional uptake of (18)F-FDG after intravenous injection. METHODS: To
      understand the mechanism responsible for the increased (18)F-FDG signal, we have
      measured the uptake of tritiated deoxyglucose (DG) in neutrophils isolated from
      human peripheral blood and sought to determine which aspects of neutrophil
      function correlate with an increase in DG uptake. RESULTS: Our results show that
      formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated respiratory burst
      activity and (3)H-DG uptake are temporally dissociated, that neutrophil-priming
      agents such as tumor necrosis factor-alpha (TNFalpha) cause an identical increase
      in (3)H-DG uptake compared with fMLP without affecting respiratory burst
      activity, and that fMLP stimulation of TNFalpha-primed cells causes major
      upregulation of superoxide anion generation (O(2)(-)) yet no incremental increase
      in (3)H-DG uptake. Furthermore, direct activation of reduced nicotinamide adenine
      dinucleotide phosphate oxidase activity with the ester phorbol 12-myristate 13
      acetate resulted in a concentration-dependent loss of cell-associated (3)H-DG,
      and preincubation of neutrophils with the phosphoinositide 3-kinase inhibitor
      wortmannin, which abolished both agonist-stimulated superoxide anion generation
      and degranulation, had no effect on TNFalpha- or fMLP-stimulated (3)H-DG uptake.
      In contrast, the fMLP-stimulated change in neutrophil shape was not influenced by
      priming or wortmannin, and of the functional responses examined, this appeared to
      correlate most closely with (3)H-DG uptake. CONCLUSION: DG uptake occurs in both
      primed and activated neutrophils. It does not correlate with respiratory burst or
      secretory activity but may reflect the polarization and migrational status of
      these cells. These data have important implications for the analysis of (18)F-FDG
      signals in vivo.

PMID- 11994531
TI  - Increased (18)F-FDG uptake in a model of inflammation: concanavalin A-mediated
      lymphocyte activation.
AB  - The aim of this project was to study a mechanism that might explain the increased
      uptake of (18)F-labeled FDG seen in inflammation. The approach chosen was to
      examine the effect on (18)F-FDG uptake of acute activation of murine lymphocytes
      by concanavalin A (Con A). METHODS: Immunocompetent BALB/c mice and nude mice
      received an intravenous injection of 10 mg/kg Con A. Twenty-four hours later, the
      mice received an intravenous injection of 0.74 MBq (20 microCi) (18)F-FDG. One
      hour later, biodistribution was determined. The distribution of the radiolabel in
      the liver was also evaluated by autoradiography. In vitro (18)F-FDG uptake to
      splenocytes from BALB/c mice with and without Con A pretreatment were determined
      30, 60, and 120 min after the splenocytes were mixed with (18)F-FDG (0.74 MBq [20
      microCi]/200 microL). RESULTS: In immunocompetent BALB/c mice, pretreatment with
      Con A significantly increased (18)F-FDG uptake in the spleen and liver.
      Autoradiographs of the liver showed that pretreatment with Con A produced a
      specific localization of (18)F-FDG at periportal areas, where numerous sites of
      cellular infiltration were observed. In vitro binding of (18)F-FDG to the
      splenocytes was significantly higher for Con A-pretreated BALB/c mice than for
      control mice. CONCLUSION: This study showed that Con A increased (18)F-FDG
      uptake. Con A-activated lymphocytes actively took up (18)F-FDG both in vitro and
      in vivo, and (18)F-FDG specifically accumulated in Con A-mediated acute
      inflammatory tissues.

PMID- 11994532
TI  - Arbutamine stress perfusion imaging in dogs with critical coronary artery
      stenoses: (99m)Tc-sestamibi versus (201)Tl.
AB  - Having previously shown that dobutamine reduces (99m)Tc-methoxyisobutylisonitrile
      (sestamibi [MIBI]) uptake in normal myocardium by elevating intracellular
      calcium, we hypothesized that arbutamine, which has less inotropic effect than
      dobutamine, might cause less reduction in MIBI uptake, thereby improving defect
      contrast. In this study using a canine model, we compared the effects of
      arbutamine stress on myocardial blood flow, myocardial MIBI uptake, and systolic
      thickening in the presence of a coronary artery stenosis. METHODS: Arbutamine was
      infused (0.5-250 ng/kg/min) in 8 open-chest dogs with critical coronary stenoses
      that abolished flow reserve. At the time of peak arbutamine effect, MIBI (296
      MBq), (201)Tl (27.75 MBq), and microspheres were coinjected. The dogs were killed
      5 min later, and myocardial tracer activities and flow were quantified by well
      counting. Ex vivo imaging of heart slices was also performed. RESULTS: Arbutamine
      increased mean heart rate, peak positive left ventricular pressure and its first
      time-derivative, and normal-zone myocardial thickening. Stenotic zone flow and
      thickening did not increase during arbutamine infusion. MIBI uptake versus flow
      was significantly lower than (201)Tl uptake at the same flow values. By imaging,
      defect magnitude (stenotic/normal) was greater for (201)Tl than MIBI (0.57 vs.
      0.77; P < 0.001) [corrected]. CONCLUSION: In the presence of coronary stenoses
      that abolished regional flow reserve, myocardial uptake of MIBI, compared with
      (201)Tl, significantly underestimated the arbutamine-induced flow heterogeneity.
      The attenuation of MIBI uptake and diminished defect contrast during arbutamine
      stress were comparable with those previously reported for dobutamine stress.

PMID- 11994533
TI  - Iodination of annexin V for imaging apoptosis.
AB  - Our goal in this investigation was to develop a method for iodinating annexin V
      that would be suitable for the in vivo detection of apoptosis. METHODS: Annexin V
      was iodinated with (125)I using 2 different techniques: direct iodination with
      IODO-BEADS, resulting in the iodination of tyrosine residues; and use of the
      Bolton-Hunter reagent, which binds to lysine. The active fraction of the labeled
      preparation was purified by affinity chromatography. We assessed thyroid
      accumulation of free iodide by comparing mice with blocked and unblocked
      thyroids. We tested the ability of iodinated annexin V to bind apoptotic cells in
      vitro using irradiated neuroblastoma cells and immobilized phosphatidylserine and
      in vivo using C3H mice subjected to whole-body irradiation. RESULTS: The
      efficiency of IODO-BEADS iodination was just below 30%; with the Bolton-Hunter
      protocol we were able to achieve 40% efficiency. When the IODO-BEADS-labeled
      preparation was injected into nude mice, activity accumulated rapidly in the
      thyroid. Two hours after injection, uptake in the thyroid region was clearly
      visible on a gamma-camera scan. This uptake was absent in mice that had had their
      thyroids blocked. We concluded that the IODO-BEADS method of labeling resulted in
      a protein that was rapidly deiodinated in vivo. By contrast, when annexin V was
      labeled using the Bolton-Hunter protocol, there was no evidence of activity
      accumulating in the thyroid. The Bolton-Hunter-labeled annexin V bound to
      apoptotic cells and immobilized phosphatidylserine in vitro. The active fraction
      of Bolton-Hunter-labeled annexin V was approximately 0.75. In C3H mice given 5-Gy
      whole-body irradiation, there was a significant induction of apoptosis in the
      spleen, as measured by the terminal deoxynucleotidyl transferase deoxyuridine
      triphosphate nick-end labeling assay, and a 4-fold increase in (125)I activity in
      the spleens relative to that of the control animals. CONCLUSION: Direct
      iodination of annexin V on tyrosine residues is a poor technique suffering from
      rapid deiodination in vivo. With Bolton-Hunter chemistry, one can produce a
      molecule that retains its label in vivo and binds to apoptotic cells in vitro and
      in vivo.

PMID- 11994535
TI  - Targeted therapy of cancer with radiolabeled antibodies.
AB  - This review focuses on the use of radiolabeled antibodies in the therapy of
      cancer, termed radioimmunotherapy (RAIT). Basic problems concerning the choice of
      antibody and radionuclide and the physiology of tumor and host are discussed.
      Then follows a review of pertinent clinical publications on various radioantibody
      constructs in the treatment of hematopoietic and solid tumors of diverse
      histopathologies, grades, and stages, and in different clinical settings. Factors
      such as dose rate delivered, tumor size, and radiosensitivity play a major role
      in determining therapeutic response, while target-to-nontarget ratios and,
      particularly, circulating radioactivity to the bone marrow determine the major
      dose-limiting toxicities. RAIT appears to be gaining a place in the therapy of
      hematopoietic neoplasms, such as non-Hodgkin's lymphoma, with several agents
      advancing in clinical trials toward registration, of which one has just been
      approved by the FDA. Although RAIT of solid tumors has shown less progress,
      pretargeting strategies, such as an affinity-enhancement system consisting of
      bispecific antibodies separating targeting from delivery of the radiotherapeutic,
      appear to enhance tumor-to-nontumor ratios and may increase rad doses to tumor
      more selectively than directly labeled antibodies.

PMID- 11994534
TI  - Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter
      radioligands under various experimental conditions.
AB  - There has been considerable interest in the development of a PET radioligand
      selective for the serotonin (5-hydroxytryptamine [5-HT]) transporter (SERT) that
      can be used to image 5-HT neurons in the living human brain. The most widely used
      SERT radiotracer to date, trans-1,2,3,5,6,10-beta-hexahydro-6-[4
      (methylthio)phenyl[pyrrolo-[2,1-a]isoquinoline ((+)-(11)C-McN5652), has been
      successful in this regard but may have some limitations. Recently, another
      promising SERT radiotracer, 3-(11)C-amino-4-(2
      dimethylaminomethylphenylsulfanyl)benzonitrile ((11)C-DASB), has been described.
      The purpose of this study was to compare and contrast (+)-(11)C-McN5652 and (11)C
      DASB under various experimental conditions. METHODS: Radioligand comparisons were
      performed in a control baboon, a baboon with reduced SERT density ((+/-)-3,4
      methylenedioxymethamphetamine [MDMA] lesion), and a baboon with reduced SERT
      availability (paroxetine pretreatment). Under each of these experimental
      conditions, repeated (triplicate) PET studies were performed with each ligand.
      RESULTS: Both radiotracers bound preferentially in brain regions known to contain
      high SERT density. For both ligands, there was a high correlation between the
      amount of regional brain ligand binding and the known regional brain
      concentration of SERT. Binding of both ligands was decreased after MDMA
      neurotoxicity (reduced SERT density), and (+)-(11)C-McN5652 and (11)C-DASB were
      comparably effective in detecting reduced SERT density after MDMA-induced 5-HT
      neurotoxicity. Pretreatment with paroxetine dramatically altered the metabolism
      and kinetics of both tracers and appeared to displace both ligands primarily from
      regions with high SERT density. Compared with (+)-(11)C-McN5652, (11)C-DASB had
      higher brain activity and a faster washout rate and provided greater contrast
      between subcortical and cortical brain regions. CONCLUSION: (11)C-DASB and (+)
      (11)C-McN5652 are suitable as PET ligands of the SERT and for detecting MDMA
      induced 5-HT neurotoxicity. (11)C-DASB may offer some advantages. Additional
      studies are needed to further characterize the properties and capabilities of
      both ligands in health and disease.

PMID- 11994536
TI  - Improved planning of radioiodine therapy for thyroid cancer.

PMID- 11994537
TI  - The role of endothelial cells in the pathogenesis of ovarian hyperstimulation
      syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of
      treatment with fertility drugs. Using human lung microvascular endothelial cells
      (HUMEC-L) as an in-vitro model of OHSS, we have tested the hypothesis that the
      endothelium is a target of HCG in the pathogenesis of OHSS. Since OHSS is
      characterized by increased capillary permeability, we have investigated the
      production and action of vasoactive agents. When HUMEC-L were cultured with high
      doses of estradiol (E(2)), no significant changes were observed in the secretion
      of vascular endothelial growth factor (VEGF), interleukin (IL)-6 or IL-1 beta.
      However, the addition of HCG resulted in a significant increase in the secretion
      of VEGF and IL-6. Time-course experiments showed that VEGF was secreted within
      minutes of HCG addition, whereas IL-6 was significantly increased only after 48 h
      in culture. The secretion of IL-1 beta was unchanged by these hormonal
      conditions. The presence of HCG receptors was demonstrated in HUMEC-L in basal
      conditions as well as after the addition of E(2). The expression of VEGF
      receptors was also investigated. High doses of E(2) were unable to increase the
      expression of KDR, flt-1 and sfl-t, but the addition of HCG significantly
      upregulated the KDR concentration in endothelial cells, while no change was
      observed for flt. Permeability assays demonstrated that while E(2) alone did not
      change the arrangement of HUMEC-L in vitro, the presence of HCG caused changes in
      the actin fibres corresponding to increased capillary permeability. Anti-human
      VEGF antibodies were able to overcome these changes. In conclusion, these
      experiments show that the endothelium may be a primary target of HCG, causing an
      acute release of VEGF and a significant increase in IL-6 and resulting in an
      autocrine-paracrine action that may increase vascular permeability.

PMID- 11994538
TI  - Study of the HIV-1 receptors CD4, CXCR4, CCR5 and CCR3 in the human and rat
      testis.
AB  - Sexual transmission of HIV is one of the main routes of transmission of AIDS.
      Despite the fact that the virus has been found in the semen and germ cells of
      patients with HIV, little is known about how the virus infects the cells of the
      genital tract. We studied the cellular distribution of CD4, a receptor necessary
      for HIV infection, and the major HIV co-receptors CCR3, CCR5 and CXCR4 in the rat
      and human testis. We used RT-PCR, Northern blotting and immunohistochemistry to
      demonstrate that CCR3 is absent from the testes of both species, whereas CCR5 and
      CXCR4 are present on the resident testicular macrophages in the interstitial
      space but not in the germ cell line. All of the human testicular macrophages
      expressed the markers CD45 and MAC387 and most also expressed CD4. Thus, our data
      suggest that macrophages in the testis may be infected by HIV and that these
      macrophages may be a site of early viral localization and a potential HIV
      reservoir. This may in turn alter the activity of Leydig cells and subsequently
      affect spermatogenesis.

PMID- 11994539
TI  - FSH-regulated gene expression profiles in ovarian tumours and normal ovaries.
AB  - Development, growth and function of the ovary are controlled by endocrine and
      paracrine signals. These may also influence the development of ovarian cancer.
      The aim of this study was to identify the key molecular markers of the
      unregulated growth and hormone synthesis seen in ovarian tumours, particularly in
      granulosa cell tumours (GCT). Genes used in this study were chosen on the basis
      of our understanding of growth and differentiation in the normal ovary. We sought
      to define the patterns of gene expression in a panel of epithelial and stromal
      ovarian tumours. Expression was determined by RT-PCR using gene-specific primers
      for the FSH receptor (FSHR); the FSH early response genes: regulatory subunit of
      protein kinase A (RII-beta), cyclin D2 (cycD2) and sgk; and late response
      markers: cyclooxygenase-2 (COX-2) and the LH receptor (LHR). The GCT had high
      expression of FSHR compared with normal ovaries and the other tumours. cycD2 and
      RII-beta and COX-2 genes were also highly expressed in the GCT. sgk and LHR
      expression was lower in all of the tumours than in normal ovaries. Serous
      cystadenocarcinomas also had an unexpectedly high expression of COX-2. Comparison
      of the gene expression profiles between each tumour group suggests a molecular
      phenotype for GCT that is similar to that reported for FSH stimulated pre
      ovulatory granulosa cells.

PMID- 11994540
TI  - Proacrosin-deficient mice and zona pellucida modifications in an experimental
      model of multifactorial infertility.
AB  - In humans, male and female partners contribute more or less equally to the
      infertility problem. In approximately 20% of infertile couples, the concurrence
      of male and female factors is suggested to be responsible for infertility.
      Neither of these factors are known nor is there a model system to prove this
      assumption. We present such a model system in the mouse, in which the lack of
      acrosin in the male and modifications of the zona pellucida (ZP) in the female
      result in a significant reduction of the fertilization rate in vitro. We
      generated mice carrying a deletion in the proline-rich region (PRR) of the
      proacrosin gene, resulting in the absence of proacrosin in the homozygous PRR(-/
      ) male mouse. Under normal conditions, sperm from the proacrosin-deficient mice
      are still capable of ZP penetration and fertilization. In this study,
      modifications of the ZP of oocytes after superovulation were achieved by
      treatment with dimethylsulphoxide or aroclor-1254 or by in-vitro ageing. It is
      known that under these conditions, a time-dependent hardening of the ZP occurs.
      The rates of fertilization in vitro of treated and aged oocytes using sperm from
      PRR(-/-) mice were found to be significantly reduced when compared with those
      reached with wild-type sperm. The relevance of the acrosin status and ZP
      condition for fertilization success were further substantiated by the finding
      that the fertilization rate with PRR(-/-) sperm is affected by the thickness of
      the ZP. Our results demonstrate that the lack of acrosin in sperm in combination
      with modifications to the ZP can affect fertility and can be an experimental
      model for the study of unexplained infertility in human couples in which both
      male- and female-derived factors are suggested to be the underlying causes.

PMID- 11994541
TI  - Erythropoietin and erythropoietin receptor expression in human endometrium
      throughout the menstrual cycle.
AB  - Erythropoietin (Epo) is an important regulator of erythropoiesis. Recent studies
      have demonstrated non-classical sites of Epo and Epo-receptor (Epo-R) expression,
      suggesting new physiological roles unrelated to erythropoiesis. Other studies
      have shown that the mouse uterus expresses Epo and its receptor, and produces Epo
      protein in an estrogen-dependent manner. We therefore hypothesized that Epo is
      one of the growth factors involved in cyclic endometrial changes. We determined
      Epo and Epo-R mRNA expression in isolated endometrial epithelial and stromal
      cells using RT-PCR. While both Epo and Epo-R were detected in all samples of
      isolated epithelial cells analysed throughout the menstrual cycle, neither one
      was detected in isolated stromal cells. In addition, using quantitative real-time
      RT-PCR with the TaqMan detection system, we showed that isolated epithelial cells
      had higher Epo mRNA levels in the secretory phase than in the proliferative
      phase. Immunohistochemical analyses revealed that Epo and Epo-R protein
      expression in glandular epithelial cells was increased during the mid
      proliferative phase and was maintained during the late proliferative and the
      early, mid- and late secretory phases. These findings suggest that Epo may be
      involved in cyclic proliferation and differentiation of endometrial glandular
      epithelial cells, acting in an autocrine manner. In addition, we also hypothesize
      that ovarian steroids may stimulate Epo production in human endometrial glandular
      epithelial cells.

PMID- 11994542
TI  - Hormonal regulation of apoptosis and the Fas and Fas ligand system in human
      endometrial cells.
AB  - The process of apoptosis is responsible for normal cellular turnover in numerous
      tissues throughout the body. The endometrial layer of the uterus shows steroid
      dependent cyclic changes in structure and function. After a proliferative and
      secretory phase, steroid support is withdrawn and the uterine epithelium is shed.
      We hypothesize that the apoptosis observed in endometrial cells following
      hormonal withdrawal is mediated by the Fas/Fas ligand (FasL) system. Normal
      endometrial cells and endometrial cancer cells were cultured in the presence of
      estrogen and progesterone. In order to mimic physiological hormonal changes,
      estrogen and progesterone were removed from the media. Apoptosis was determined
      by 3-[4,5-dimethylthiazol-2-yl]-2,5-dephenyl tetrazolium bromide (MTT) assay and
      propidium iodide staining, while Fas and FasL expression were evaluated by
      Western blot analysis. The endometrial cells expressed Fas and low levels of
      FasL. Withdrawal of estrogen and/or progesterone from the culture induced
      apoptosis causing an approximately 50% decrease in cell viability. This coincided
      with increased Fas and FasL expression. Treatment of the cells with anti-FasL
      antibody prevented cell death following hormonal withdrawal. Estrogen and
      progesterone therefore represent survival factors which hamper cell death by
      impeding the expression of apoptotic factors. Our results indicate that Fas
      mediated apoptosis is important for endometrial cycling and suggest that
      dysregulation of the Fas/FasL interactions may have an important role in the
      development of endometrial cancer.

PMID- 11994543
TI  - Increased leptin expression in endometriosis cells is associated with endometrial
      stromal cell proliferation and leptin gene up-regulation.
AB  - Endometriosis is a polygenic disease with complex, multifactorial aetiologies
      affecting approximately 10% of women of reproductive age. Leptin is the product
      of the ob gene, which is related to reproductive function and immunological
      alteration. The angiogenic and mitogenic action of leptin may influence the
      formation of endometriosis. This study was aimed at determining whether leptin
      and leptin receptor expression differs in eutopic and ectopic endometria
      collected from laparoscopy and at investigating the pathophysiological role of
      leptin in the development of endometriosis. Leptin mRNA was undetectable in seven
      out of 14 eutopic endometria and only a minute amount was detected in the
      remaining samples. In contrast, there was a marked increase in leptin mRNA and
      protein expression in ectopic endometriotic lesions of patients with
      endometriosis (P < 0.05). Receptors for leptin were immunologically stained in
      eutopic endometrium as well as in ectopic endometriotic implants. However, the
      levels of mRNA for the long and total forms of leptin receptors were suppressed
      in association with the severity of endometriosis (P < 0.05). Administration of
      leptin stimulated its own mRNA expression in ectopic endometriotic stromal cells
      but decreased steady-state concentrations of mRNA encoding for leptin receptor (n
      = 6). In addition, leptin significantly enhanced both eutopic and ectopic
      endometrial stromal cell proliferation (P < 0.05). In conclusion, the
      differential distribution of mRNA for leptin and its receptor suggests an
      important autocrine and paracrine role for leptin in human endometriosis. The
      mitogenic and auto-augmentation effects of leptin may further contribute to the
      pathogenesis of endometriosis.

PMID- 11994544
TI  - Expression of MAPkinases (Erk1/2) during decidualization in the rat: regulation
      by progesterone and nitric oxide.
AB  - The interaction between nitric oxide (NO), progesterone and the MAPkinase
      signalling pathway involved in decidualization was studied using
      immunohistochemistry during implantation in the rat. Early pregnant rats were
      treated with the inhibitor of nitric oxide synthesizing enzyme iNOS,
      aminoguanidine, either alone or in combination with the low dose antiprogestin,
      onapristone. The combined treatment was most effective on days 7 and 9 post
      coitum leading to a complete loss of embryos. The expression pattern of activated
      MAPkinases, Erk1/2 and iNOS appeared to be associated with the differentiation
      process of decidualization. A maximum staining of both enzymes was observed on
      day 9 post coitum in the mesometrial decidua. In addition, Erk1/2 and iNOS were
      highly coexpressed around the mesometrial sinusoids. Combined treatment with
      aminoguanidine and onapristone for 3 days led to a transient suppression of
      Erk1/2 and abolished Cox2 expression. Concomitantly, angiogenesis was reduced and
      dilated sinusoids were missing in the mesometrial decidua. In conclusion, our
      study suggests that (i) the member of the mitogen-activated protein kinase (MAPK)
      family, Erk1/2, is activated during implantation and may play an important role
      during the decidualization process, and (ii) this enzyme may be regulated by both
      progesterone and NO.

PMID- 11994545
TI  - Global analysis of differentially expressed genes in early gestational decidua
      and chorionic villi using a 9600 human cDNA microarray.
AB  - The global gene expression profiles of the decidua and chorionic villi of early
      human pregnancies were analysed by using cDNA microarray technology. Decidual and
      villous placental tissues were obtained from first trimester abortus and mRNA was
      extracted for cDNA microarray analysis. The human cDNA microarray [9600 clones,
      including known regulatory genes and expressed sequence tags (EST)] with
      colorimetric detection was used to identify differentially expressed genes
      between early gestational decidua and villi. According to cDNA microarray
      analysis, we have identified 641 genes with highly expressed mRNA in both decidua
      and villi, 49 genes with higher expressions in decidua, and 75 genes with higher
      expression in chorionic villi. These differentially expressed genes were further
      grouped into categories by their putative functions, including: cell growth
      related factors, hormones/cytokines, cell adhesion molecules, signal transduction
      molecules, apoptosis-related factors, cytoskeleton/extracellular matrix proteins,
      and EST. Immunohistochemical stainings of cathepsin L, leukaemia inhibitory
      factor-receptor, and proliferative cell nuclear antigen showed results consistent
      with the microarray data. Identification of the differentially expressed genes
      between decidua and villi by microarray provide a global profiling of the gene
      expression pattern. This work adds to our understanding of placentation by
      reporting the gene expression profiles during first trimester human pregnancies
      using cDNA microarray.

PMID- 11994546
TI  - Human choriocarcinoma cell line JEG-3 produces and secretes active retinoids from
      retinol.
AB  - Vitamin A (retinol) and its active derivatives (the retinoids) are essential for
      growth and development of the mammalian fetus. Maternally-derived retinol has to
      pass through the placenta to reach the developing fetus. Despite its apparent
      importance, little is known about placental metabolism of retinol, and
      particularly placental production and/or secretion of active retinoids. It has
      been previously considered that retinoids are recruited from the uterine
      environment to influence placental development and function during gestation. We
      have studied retinoid metabolism in the human choriocarcinoma cell line JEG-3 and
      demonstrate, for the first time, that active retinoids are produced endogenously
      by the JEG-3 cell line from retinol. These retinoids induce gene expression from
      a retinoic acid-responsive enhancer element reporter plasmid and modulate
      placental transglutaminase activity. Furthermore, retinoids are secreted from JEG
      3, as shown by the activation of retinoic acid-responsive beta lacZ reporter
      cells grown in conditioned media. These results suggest that there could be an
      active role for trophoblast-derived retinoids during human development.

PMID- 11994547
TI  - A polymorphism in the matrix metalloproteinase-9 promoter is associated with
      increased risk of preterm premature rupture of membranes in African Americans.
AB  - Fetal membrane rupture is associated with increased expression of matrix
      metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the
      functional significance of a variable number tandem repeat and a single
      nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their
      association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat
      allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial
      cells and WISH amnion-derived cells, but in THP-1 monocyte/macrophage cells the
      14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not
      significantly affect promoter activity. A case-control study of African American
      neonates revealed that the 14 CA-repeat allele was more common in newborns
      delivered of mothers who had PPROM than in those delivered at term. There was no
      association between the -1562 SNP and PPROM. We conclude that there are cell host
      dependent differences in MMP-9 promoter activity related to CA-repeat number and
      that fetal carriage of the 14 CA-repeat allele is associated with PPROM in
      African Americans.

PMID- 11994548
TI  - Single cell CGH analysis reveals a high degree of mosaicism in human embryos from
      patients with balanced structural chromosome aberrations.
AB  - We have performed comparative genomic hybridization (CGH) analysis of single
      blastomeres from human preimplantation embryos of patients undergoing
      preimplantation genetic diagnosis (PGD) for inherited structural chromosome
      aberrations and from embryos of IVF couples without known chromosomal
      aberrations. The aim was to verify the PGD results for the specific
      translocation, reveal the overall genetic balance in each cell and visualize the
      degree of mosaicism regarding all the chromosomes within the embryo. We
      successfully analysed 94 blastomeres from 28 human embryos generated from 13
      couples. The single cell CGH could verify most of the unbalanced translocations
      detected by PGD. Some of the embryos exhibited a mosaic pattern regarding the
      chromosomes involved in the translocation, and different segregation could be
      seen within an embryo. In addition to the translocations, we found a high degree
      of numerical aberrations including monosomies, trisomies and duplications or
      deletions of parts of chromosomes. All of the embryos (100%) were mosaic,
      containing more than one chromosomally uniform cell line, or even chaotic with a
      different chromosomal content in each blastomere.

PMID- 11994549
TI  - Cloning and the U.S. Congress.

PMID- 11994550
TI  - European perspectives on therapeutic cloning.

PMID- 11994551
TI  - Stem cells--scientific, medical, and political issues.

PMID- 11994552
TI  - British Thoracic Society Guidelines for the Management of Community Acquired
      Pneumonia in Childhood.

PMID- 11994553
TI  - Home international normalized ratio monitoring: where evidence-based medicine is
      exemplified in the Medicare coverage process.

PMID- 11994554
TI  - Precordial ST-segment depression in inferior myocardial infarction is associated
      with slow flow in the non-culprit left anterior descending artery.
AB  - BACKGROUND: Anterior precordial ST-segment depression (APSTD) is common in the
      setting of inferior myocardial infarction (IMI). The presence of APSTD correlates
      with increased risk of adverse outcomes in patients with acute IMI as well as
      more myocardium at risk as assessed by sestamibi, larger infarcts, lower ejection
      fractions, and more severe wall motion abnormalities in the infarct region. The
      ECG leads associated with APSTD (V1-V3) are generally thought to represent
      electrical activity subtended by the anterior myocardium, which is perfused by
      the left anterior descending artery (LAD). To determine whether APSTD is
      associated with abnormal blood flow in the uninvolved or non-culprit LAD, we
      assessed TIMI flow grades and corrected TIMI frame counts (CTFC) in both the
      culprit and non-culprit arteries of IMI patients. METHODS: Data were drawn from
      the TIMI 10B trial of tenecteplase versus front-loaded tissue plasminogen
      activator in acute MI. Baseline ECGs were obtained within 12 hours of symptom
      onset, and angiography was performed 90 minutes following thrombolytic
      administration. A patient was considered to have precordial ST-segment depression
      if any ST-segment depression was present in any of leads V1-V3. RESULTS: The
      majority of IMI's were due to right coronary artery occlusions, both in patients
      with APSTD (79.6%) and without APSTD (77.9%). In patients in whom the LAD was not
      the culprit artery but with APSTD were significantly less likely to have TIMI 3
      flow at 90 minutes and more likely to have TIMI 2 flow. There was a trend toward
      slower CTFC in APSTD patients (27.2 +/- 13.4 vs. 22.6 +/- 8.5 frames/sec, p =
      0.07). CONCLUSIONS: Among patients with acute IMI associated with precordial ST
      segment depression, flow in the non-culprit left anterior descending artery was
      slower than that in patients without APSTD. This finding may partially explain
      the occurrence of APSTD in IMI.

PMID- 11994555
TI  - Platelet glycoprotein Ib alpha receptor polymorphisms and recurrent ischaemic
      events in acute coronary syndrome patients.
AB  - AIMS: To examine the relationship between polymorphisms in the platelet receptor
      glycoprotein (GP) Ib(alpha) and recurrent ischaemic events, and assess their
      impact on response to anti-platelet treatment. METHODS AND RESULTS: 1014 patients
      presenting with unstable coronary syndrome were recruited from the OPUS-TIMI 16
      clinical trial of the platelet GPIIb/IIIa antagonist, orbofiban. The subjects
      were genotyped for two polymorphisms in the gene for GPIb(alpha). These were a T
      5C polymorphism in the 5' untranslated Kozak region of the GPIb(alpha) gene, and
      the variable number of tandem repeats (VNTR) in the macroglycopeptide region.165
      patients had events (recurrent ischaemia, urgent revascularisation, myocardial
      infarction (MI), stroke and death). There was no effect of the number of -5C
      alleles on composite endpoint frequency among Caucasian subjects (test for trend,
      p = 0.47). However, MI risk increased with the number of -5C alleles carried,
      with MI occurring in 2.3% of patients with the -5T/-5T genotype, 5.0% of -5T/-5C,
      and 16.7% of -5C/-5C (p < 0.01). The effect of treatment on MI outcome was not
      significantly modified by genotype (test for interaction, p = 0.10). The overall
      risk of bleeding was not strongly influenced by either the -5C or the VNTR
      polymorphisms. CONCLUSION: In an unstable coronary syndrome population the T-5C
      polymorphism in GPIb(alpha) influences risk of subsequent MI.

PMID- 11994556
TI  - Use of thrombolytic therapy for acute myocardial infarction: effects of gender
      and age on treatment rates.
AB  - BACKGROUND: Although there have been efforts to increase the utilization of
      thrombolytic therapy, there are still many patients who might benefit from this
      treatment who do not receive it. Women and the elderly have been particularly
      undertreated, despite evidence that their survival can be improved with
      thrombolysis. This study was undertaken to determine the relative rates of
      treatment of women vs. men and the elderly vs. younger subjects and to examine
      factors that might explain differences in treatment frequency. METHODS AND
      RESULTS: This is a retrospective study of patients who presented to the Emergency
      Departments of four local hospitals in 1993 and 1994 with evidence for acute ST
      elevation myocardial infarction. Demographic data, past medical history,
      information on co-morbid illnesses, and times to hospital arrival, first
      electrocardiogram, physician notification, and thrombolytic therapy were recorded
      as was survival to hospital discharge. Data for patients who did or did not
      receive thrombolytic therapy were compared. Men were treated more frequently in
      both tertiary and community hospitals. Women were older, but within each age
      bracket, men were treated more often. The time of arrival was similar for men and
      women, but men who arrived within 6 hours or 6-12 hours after pain onset were
      treated at a higher rate than women. For patients without contraindications,
      treatment was not affected by gender or age. However, treatment rates decreased
      with increased prevalence of exclusionary factors, and since both women and the
      elderly tended to have more such factors, elderly women were treated at a
      markedly lower rate. The single clinical factor that increased thrombolytic usage
      in women compared to men was a history of prior myocardial infarction.
      CONCLUSION: Despite convincing evidence that thrombolytic therapy is beneficial
      in women and the elderly, these groups have been relatively neglected unless
      attention is called to clinical risk, for example, by history of prior myocardial
      infarction.

PMID- 11994557
TI  - Polyethylene glycol diisocyanate decreases platelet deposition after balloon
      injury of rabbit femoral arteries.
AB  - BACKGROUND: Platelet deposition after angioplasty remains problematic and may
      contribute to intimal hyperplasia and restenosis. We proposed that polyethylene
      glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages
      with amine residues on proteins, could mask thrombogenic vascular wall proteins
      from platelets, thereby abrogating acute platelet deposition. METHODS AND
      RESULTS: To test this hypothesis, we isolated the femoral arteries of 10 New
      Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter
      which was inserted through a distal arteriotomy. Immediately after balloon
      injury, (111)indium-labeled autologous platelets were infused peripherally and
      the injured femoral arteries were randomly treated for 1 minute with a PEG-DISO
      solution in one artery and a control solution of the phosphate buffered saline
      vehicle in the contralateral artery. Following treatment, reflow was initiated.
      The vessels were harvested after 1 hour and radioactivity was quantified in a
      gamma counter. Platelet counts were standardized by weight and expressed as
      platelets/mg (mean +/- SEM). Platelet deposition onto arteries treated with PEG
      DISO was (1.2 +/- 0.5) x 10(6) platelets/mg compared to (5.6 +/- 4.2) x 10(6)
      platelets/mg onto the contralateral control arteries treated with vehicle (P <
      0.005). Scanning electron micrographs of the injured vessel segment confirmed
      qualitatively less platelet deposition on the treated segments than on the
      control segments. CONCLUSION: Treatment with PEG-DISO significantly inhibited
      platelet deposition after vascular injury. These data support the hypothesis that
      treatment with PEG-DISO masks surface adhesive proteins from platelet receptors
      in vivo and that the resulting molecular barrier significantly reduces platelet
      deposition onto the damaged vessel wall for at least one hour. The formation of a
      molecularly thin barrier to platelet deposition may thus be a novel and effective
      treatment to abrogate acute intravascular thrombosis and may have value in the
      treatment of restenosis.

PMID- 11994558
TI  - Glycoprotein IIb/IIIa combination therapy in acute myocardial infarction:
      tailoring therapies to optimize outcome.
AB  - Numerous randomized trials have unequivocally shown that fibrinolytic therapy in
      the treatment of ST-segment elevation myocardial infarction substantially reduces
      mortality when administered within 12 hours of symptom-onset. Although
      fibrinolytic therapy initially restores antegrade flow in the infarct vessel in
      the majority of patients, sustained tissue-level reperfusion occurs in only
      approximately 25% of patients. Thrombin and platelets are two additional
      constituents of a coronary thrombus that contribute to the tendency for vessel
      reocclusion after initially successful reperfusion. Therefore, adjunctive therapy
      with potent antithrombins and antiplatelets is essential in the successful
      treatment of a coronary thrombus. Recent studies including GUSTO-V and ASSENT-III
      have studied the use of combination drug therapy with glycoprotein IIb/IIIa
      inhibition and reduced-dose fibrinolytics in the treatment of acute myocardial
      infarction. These studies demonstrated that combination therapy reduces
      reinfarction rates. However, this therapy is associated with increased bleeding
      complications especially in elderly patients. This article reviews the results
      and clinical implications of these major trials of combination drug therapy in
      acute myocardial infarction and provides recommendations for tailoring their use
      in clinical practice.

PMID- 11994559
TI  - Argatroban.
AB  - Antithrombotic and antiplatelet therapies are the cornerstones of management of
      cardiovascular disorders today. Due to the safety and efficacy limitations of the
      classic antithrombotic, unfractionated heparin, considerable effort has been
      directed at developing novel anticoagulants. Direct thrombin inhibitors as a
      class of drugs offer inhibition of clot-bound as well as fluid-phase thrombin and
      a more predictable anticoagulant response. Specifically, argatroban, a synthetic
      small molecule direct thrombin inhibitor, selectively inhibits the catalytic site
      of thrombin in a reversible manner. Overall, argatroban's short half-life, ease
      of monitoring with an activated partial thromboplastin time, and safety in renal
      failure patients make this drug the preferable mode therapy for prevention of
      thrombosis in heparin-induced thrombocytopenia. The role of adjunctive argatroban
      therapy in acute coronary syndromes and during percutaneous coronary intervention
      is currently being studied.

PMID- 11994560
TI  - Possible mechanisms of aspirin resistance.
AB  - Data regarding possible mechanisms of aspirin (ASA) resistance in patients with
      recurrent myocardial infarction (MI) or vascular ischemia are limited. Five major
      possible mechanisms of ASA resistance are documented in the primary literature
      and are discussed in this paper. These mechanisms include: (1) inadequate
      blockade of erythrocyte-induced platelet activation; (2) biosynthesis of F2
      isoprostane 8-iso-prostaglandin (PGF2alpha), a bioactive product of arachidonic
      acid peroxidation; (3) stimulation of platelet aggregation by cigarette smoking;
      (4) ASA resistant platelet aggregability by increased levels of norepinephrine,
      as seen during excessive exercise or periods of mental stress; and (5) increased
      platelet sensitivity to collagen. Recognizing mechanisms of platelet activation
      and identifying reversible risk factors such as smoking and mental stress may
      help decrease the occurrence of ASA resistance and possibly improve patient
      outcomes. Until more definitive data become available, when prescribing and
      dosing ASA for the prevention of MI or vascular ischemia, clinicians should
      identify possible risk factors for ASA resistance. Whether or not patients at
      risk for ASA resistance are candidates for additive antiplatelet therapy remains
      to be determined.

PMID- 11994561
TI  - Advanced prostate cancer activates coagulation: a controlled study of activation
      markers of coagulation in ambulatory patients with localized and advanced
      prostate cancer.
AB  - Cancer and increased age are risk factors for coagulation activation. Patients
      with advanced prostate cancer, which usually presents in the seventh to eighth
      decade of life, are likely to be at increased risk for thrombosis. We report
      results of a controlled study of changes in specific and sensitive markers of
      coagulation activation in patients with prostate cancer. Complete blood count,
      prothrombin time, partial thromboplastin time, prothrombin fragment 1 + 2 (F1 +
      2), thrombin-antithrombin complex (TAT) and quantitative D-dimers (DD) were
      measured in 30 patients of advanced prostate cancer (androgen ablated), in 30
      newly diagnosed localized prostate cancer patients, in 30 healthy age-matched
      volunteers, and in 20 healthy young volunteers. Plasma F1 + 2 (P < 0.05) and DD
      (P < 0.05), but not TAT, were significantly elevated in healthy elderly males
      (mean age, 77 years) when compared with healthy young volunteers (mean age, 35
      years). F1 + 2, TAT and DD were significantly elevated in advanced prostate
      cancer when compared with healthy age-matched controls (P < 0.001). In
      conclusion, advanced prostate cancer patients have significantly increased levels
      of sensitive markers of coagulation activation compared with healthy age-matched
      controls. This data can be used to plan studies to determine the risk of
      clinically significant coagulopathy and the role of primary prophylaxis in
      patients with advanced prostate cancer.

PMID- 11994562
TI  - Abnormal optical waveform profiles in coagulation assays from patients with
      antiphospholipid antibodies.
AB  - Transmittance waveforms are the optical data generated during clot formation on
      photo-optical coagulation analyzers and are used to define specific events of the
      clotting reactions. Thus, a prothrombin time (PT) or an activated partial
      thromboplastin time (aPTT) can be divided into a pre-coagulation phase, a
      coagulation phase, and a post-coagulation phase. These phases are further
      characterized by parameters that define the timing, the rate, the 'slope', and
      the magnitude of the signal change of the reactions. We investigated the
      transmittance waveform parameters obtained during PT and aPTT of patients with
      antiphospholipid antibodies (APLA) who were or were not taking warfarin, normal
      donors, and non-APLA patients taking warfarin. An abnormal deflection in the pre
      coagulation phase of the PT (called slope 1) was observed in 61.5% of the
      patients with APLA, in contrast to 5.9% of non-APLA patients taking warfarin (P=
      0.0015). The presence of an abnormal PT slope 1 was reagent specific and was
      inversely correlated with the anticardiolipin antibody immunoglobulin G (IgG)
      level, which suggests that the abnormal PT slope 1 may reflect interactions
      between patient IgG and components from the thromboplastin, possibly
      phospholipids. The abnormal PT slope 1 values may be of diagnostic utility in the
      identification of patients with antiphospholipid syndromes.

PMID- 11994563
TI  - Magnesium and manganese ions accelerate tissue factor-induced coagulation
      independently of factor IX.
AB  - The purpose of the present study was to assess the effect of magnesium and
      manganese ions on tissue factor (TF)-induced coagulation and the possible role of
      factor IX therein. When magnesium chloride or manganese chloride were added in
      low concentrations to normal human plasma, the human (recombinant) TF-induced
      coagulation time was shortened. At higher concentrations, magnesium and manganese
      prolonged the TF-induced coagulation time. Maximum shortening of the coagulation
      time was obtained at a concentration of 0.5 mmol/l Mn or 2 mmol/l Mg in plasma.
      Shortening of the TF-induced coagulation time by magnesium and manganese was also
      observed in factor IX-deficient plasma. A comparison was made between TF
      preparations from human, rabbit, and bovine brain. The accelerating effect of
      magnesium was greater with human than with rabbit brain TF. Using bovine brain
      TF, the clotting time was not shortened by magnesium. Activated factor X-induced
      coagulation of normal plasma was not accelerated by magnesium. From these
      experiments, it is inferred that activation of factor X by factor VII-TF can be
      accelerated by magnesium and manganese ions independently of factor IX.

PMID- 11994564
TI  - Genetic contribution to factor VII levels in families of patients undergoing
      coronary arteriography.
AB  - An elevated plasma level of factor VII is a risk factor for coronary artery
      disease. We investigated environmental, familial, and genetic influences on
      factor VII activity in 508 family members of 87 probands who underwent elective
      coronary arteriography. Maximum likelihood methods were used to fit several
      genetic and non-genetic models of inheritance to these data to determine whether
      an unobserved Mendelian major gene could explain the familial distribution of
      factor VII. Factor VII activities were adjusted for age, gender, body mass index,
      smoking, alcohol consumption, menopause status, and triglycerides prior to this
      segregation analysis (this model accounted for 33.5% of the total variation).
      Adjusted factor VII activities showed strong familial aggregation with an
      estimated parent-offspring correlation of 0.34, sibling correlation of 0.36 and a
      smaller spouse correlation of 0.16. Regressive models were used to test genetic
      and non-genetic models in these 87 families. Mendelian single-locus models with
      either two or three underlying genotypic distributions of factor VII activities
      were best supported by these data. Essentially, these Mendelian models suggest
      most individuals come from a low distribution (mean, 116%), with a few
      individuals homozygous for a high allele drawn from a distribution with a mean of
      166%. Future linkage studies may be worthwhile to further clarify the mechanisms
      controlling factor VII activity.

PMID- 11994565
TI  - Baseline abnormalities of endothelial function and thrombogenesis in relation to
      prognosis in essential hypertension.
AB  - The present study was designed to test the hypothesis that markers of a
      hypercoagulable state predict subsequent cardiovascular events in hypertensives.
      To do this, we performed a prospective follow-up analysis of 178 patients (86
      male; mean age, 54 years (standard deviation, 15); mean blood pressure, 188/103
      mmHg) recruited from a hypertension clinic in a city-centre teaching hospital
      serving a multi-ethnic population. The main outcome measures were clinical and
      echocardiographic details, and laboratory markers of thrombosis and haemostasis
      (fibrinogen, fibrin D-dimer, plasminogen activator inhibitor, soluble P-selectin,
      von Willebrand factor, and viscosity) that were measured at baseline. After a
      mean follow-up of 45 months (interquartile range, 37-54), 30 subjects experienced
      one of a number of endpoints that included death or adverse cardiovascular event.
      These patients were older (P<0.001) and had significantly higher plasma von
      Willebrand factor (P=0.015) and fibrin D-dimer levels (P=0.005) compared with
      those 148 who were free of endpoints at follow-up. There were no statistically
      significant differences in mean blood pressure, other measured parameters, and
      the left ventricular mass index between the groups. Using univariate 'time to
      event' analysis, only high (> or = median) baseline systolic blood pressures were
      associated with a shortened event-free survival (log rank test, P= 0.0078). We
      conclude that hypertensive patients who experienced a new cardiovascular event
      were much older and had more endothelial dysfunction and thrombogenesis than
      those who were free of complications. However, only high baseline systolic blood
      pressures were associated with a shortened event-free survival.

PMID- 11994566
TI  - Enhanced monocyte tissue factor expression in hepatosplenic schistosomiasis.
AB  - Monocyte tissue factor expression was evaluated in 67 patients with hepatosplenic
      Schistosomiasis. They were classified as Child A (n = 15), Child B (n = 15),
      Child C (n = 12) and Bleeders (n = 10), in addition to 15 healthy controls.
      Mononuclear cells were cultured in vitro with and without lipopolysaccharide
      (LPS) to assess monocyte tissue factor (TF) antigen (Ag) and activity (Act) in
      cell lysate, in addition to measurement of prothrombin fragment 1 + 2 (F1 + 2) as
      a marker of in vivo thrombin generation. A significant increase in monocyte TF Ag
      and TF Act was noted in all stages of the disease compared with the control
      group, with marked accentuation during an acute attack of variceal bleeding. This
      enhanced monocyte expression was noted before the addition of LPS and became more
      obvious with addition of LPS. An increasing level of F1 + 2 was similarly noted.
      These findings constitute further evidence for an existing prothrombotic state in
      hepatosplenic Schistosomiasis, and also that monocytes are closely implicated in
      the haemostatic diathesis characterizing the disease.

PMID- 11994567
TI  - Vitamin K deficiency and D-dimer levels in the intensive care unit: a prospective
      cohort study.
AB  - Patients in the intensive care unit (ICU) are at risk for the development of
      vitamin K deficiency. We sought to determine the frequency of this deficiency by
      performing a prospective cohort study in which patients were screened for vitamin
      K deficiency on ICU admission and every other day thereafter. Vitamin K
      deficiency was diagnosed by a functional coagulation factor II to Echis factor II
      ratio < 0.70. Activity of the coagulation cascade was measured by D-dimer. In
      total, 40 patients were enrolled into the study. Seven of the patients had ratios
      < 0.70 on the day of admission to the ICU, and three patients developed ratios <
      0.70. Thus, 10 of 40 patients (25%; 95% confidence interval, 12-38%) had vitamin
      K deficiency. Two patients developed coagulopathy, as indicated by an
      International Normalized Ratio of more than 1.4. D-dimer levels were elevated in
      86 of 111 samples. We conclude that vitamin K deficiency is common among
      critically ill patients, particularly on admission to the ICU. Our findings
      suggest that additional clinical research is warranted to determine whether
      vitamin K supplementation on admission to the ICU reduces the risk of ICU
      acquired vitamin K deficiency and its attendant complications over the course of
      the ICU stay.

PMID- 11994568
TI  - Hereditary hemorrhagic telangiectasia, factor V Leiden and antiphospholipid
      syndrome: a case report.
AB  - We report on a 57-year-old woman with three episodes of ischemic strokes and
      hereditary hemorrhagic telangiectasia (HHT). Tests for inherited and acquired
      thrombophilia showed elevated anticardiolipin immunoglobulin (Ig)M antibodies (on
      three separate occasions), anti-prothrombin IgG antibodies, and the heterozygous
      form of factor V Leiden. This is the first case of HHT, a primary
      antiphospholipid syndrome, combined with factor V Leiden. No detectable
      arteriovenous malformation was found and ischemic episodes, documented by
      computer tomography, were related to the presence of antiphospholipid antibodies
      and possibly the carriership of factor V Leiden mutation. Since aspirin provoked
      severe nasal hemorrhages, treatment with ticlopidine was initiated after the
      third stroke. Over an 18-month follow-up, ischemic episodes were absent and we
      regarded oral anticoagulation as unjustifiable.

PMID- 11994569
TI  - Retinal artery occlusion in a patient with factor V Leiden and prothrombin
      G20210A mutations.
AB  - Retinal artery occlusion is rare in young adults, and may be associated with
      hereditary thrombophilia. We present a 19-year-old male who was evaluated for
      central retinal artery occlusion and found to be homozygous for the factor V
      Leiden mutation and heterozygous for the prothrombin G20210A mutation. Anterior
      chamber paracenthesis resulted in dramatic improvement, but recurring loss of
      vision necessitated repeated paracenthesis and the addition of aspirin to
      standard anticoagulation treatment. The literature concerning hereditary
      thrombophilia and retinal artery occlusion is reviewed, and the synergistic
      effect of multiple risk factors is emphasized. Screening for hereditary
      thrombophilia should be considered for young people presenting with unexplained
      retinal artery occlusion.

PMID- 11994570
TI  - Human plasma fibrinogen measurement derived from activated partial thromboplastin
      time clot formation.
AB  - Prothrombin time-derived measurement of fibrinogen (PTd) has already been
      described. Activated partial thromboplastin time-derived measurement of
      fibrinogen (aPTTd) has not yet been clearly defined. Using an MDA II coagulometer
      (Organon Teknika, Durham, North Carolina, USA), we have therefore compared
      fibrinogen levels determined with Clauss, PTd, and aPTTd assays and an enzyme
      immunoassay (EIA) in 172 samples. Of these, 47 were from pre-operative controls,
      18 from patients with liver disease, 28 from patients with hyperfibrinogenaemia,
      33 from patients treated with vitamin K antagonists, 22 from patients treated
      with unfractionated heparin and 24 from haemophilic patients. Within the normal
      range, interassay and intra-assay variations were comparable. For control
      samples, PTd, aPTTd and Clauss assays were well correlated, without any
      systematic error. EIA was also correlated but values were slightly higher (mean
      of difference = 0.24). Pathological samples showed an overestimation of
      fibrinogen when using PTd measurements in patients treated with vitamin K
      antagonists, as well as when using aPTTd measurements in patients presenting with
      factor VIII and factor IX deficiencies. These results indicate that, despite
      expected financial savings, aPTTd fibrinogen measurements should not be used
      without restriction. PTd and aPTTd fibrinogen determinations are provided without
      any additional cost. Their comparison with Clauss fibrinogen results may
      constitute a validation tool or have additional diagnostic utility (e.g.
      identifying polymerization abnormalities in case of dissimilar results).

PMID- 11994571
TI  - Prothrombotic effects and clinical implications of third-generation oral
      contraceptives use.
AB  - Although the use of oral contraceptives has been frequently associated with an
      increased risk of thromboembolic events, definitive prothrombotic mechanisms have
      not so far been fully elucidated. The aim of our investigation was the evaluation
      of the activities of antithrombin, protein C, protein S and the resistance to
      activated protein C in 137 healthy users of third-generation oral contraceptives
      and in 170 healthy women who were not consuming oral contraceptives. Women on
      oral contraceptives showed a marked prothrombotic pattern, characterized by
      reduced activities of antithrombin and protein S, and increased resistance to
      activated protein C. Nearby 50% of oral contraceptive users displayed activities
      of protein S below the lower value of the reference range (controls, 10%; P <
      0.001). No significant differences were observed between two progestagens
      (desogestrel or gestodene) on the coagulation parameters tested. We believe that,
      due to the adverse effect on haemostasis, the administration of third-generation
      oral contraceptives should be carefully considered in women carrying
      prothrombotic abnormalities.

PMID- 11994572
TI  - Heparin and time-dependent platelet dysfunction during cardiac surgery.

PMID- 11994573
TI  - Children's art as a helpful index of anxiety and self-esteem with plastic
      surgery.
AB  - Children often cannot adequately express their feelings about physical issues
      that may be affecting them emotionally. Nonverbal communication with art has been
      a time-tested tool in understanding and interpreting the feelings of children
      under stress. For 27 years, the author has used art as a helpful index of anxiety
      and self-esteem in children undergoing plastic surgery for congenital, traumatic,
      and aesthetic problems. A child psychiatrist and an art therapist evaluated 200
      drawings. The evaluations corroborated the need to "listen" to our patients no
      matter what their size.

PMID- 11994575
TI  - Applications of a new carbonated calcium phosphate bone cement: early experience
      in pediatric and adult craniofacial reconstruction.
AB  - Hydroxyapatite cements have recently been employed as bone substitutes in
      craniofacial reconstruction. They are easily applied, nonresorbable, available in
      unlimited quantity, and eliminate donor-site morbidity. Norian CRS (craniofacial
      repair system) is a new carbonated calcium phosphate paste that is unique in that
      it more closely resembles bone than do traditional hydroxyapatite pastes. Norian
      is a low-order crystalline apatite soluble at a low pH, facilitating its
      resorption and replacement by host bone. The cement was first used for
      craniofacial surgery in North America at the Children's Hospital of Philadelphia.
      This report presents the authors' experience with this bone substitute in both
      pediatric and adult craniofacial reconstruction. Sixteen adult and pediatric
      patients underwent craniofacial reconstruction involving the use of carbonated
      calcium phosphate paste for correction of defects that required from 5 to 110 g
      of carbonated calcium phosphate paste (mean, 28.5 g). The patients were all
      followed for a minimum of 14 months. Minor complications included one case of
      infection and two cases involving cement microfragmentation. In the authors'
      experience, carbonated calcium phosphate paste has proved to be an excellent
      alloplastic material for osseous augmentation and reconstruction in the
      craniofacial skeleton. Few problems were encountered using this material; no
      significant morbidity was encountered. Although this material seems to be
      promising as a bone substitute, further follow-up will be necessary to evaluate
      its potential role in craniofacial surgery.

PMID- 11994576
TI  - Midface distraction following Le Fort III and monobloc osteotomies: problems and
      solutions.
AB  - Distraction osteogenesis has been used increasingly for midfacial advancement in
      patients with syndromic craniosynostosis and in severe developmental hypoplasia
      of the midface. In these patients, the degree of advancement required is often so
      great that restriction of the adjacent soft tissues may preclude stable
      advancement in one stage. Whereas distraction is an ideal solution by which to
      gradually lengthen both the bones and the soft tissues, potential problems remain
      in translating the distraction forces to the midface. In these patients, severe
      developmental hypoplasia may be associated with weak union between the zygoma and
      the maxilla, increasing the chance of zygomaticomaxillary dysjunction when using
      internal devices that translate distraction force to the maxilla through the
      zygoma. Eight cases are reported in which either internal or external distraction
      systems were used for midface advancement following Le Fort III (n = 7) or
      monobloc (n = 1) osteotomies. Cases of patients in whom hypoplasia at the
      zygomaticomaxillary junction altered or impaired plans for midface distraction
      were reported from three host institutions. Seven patients had midface hypoplasia
      associated with syndromic craniosynostosis, and one patient had severe
      developmental midface hypoplasia. The distraction protocol was modified to
      successfully complete midface advancement in light of weakness at the
      zygomaticomaxillary junction in seven patients. Modifications included change
      from an internal to an external distraction system in two patients, rigid
      fixation and bone graft stabilization of the midface in one patient, and plate
      stabilization of a fractured or unstable zygomaticomaxillary junction followed by
      resumption of internal distraction in four patients. Previous infection and bone
      loss involving both malar complexes precluded one patient from being a candidate
      for an internal distraction system. Using a problem-based approach, successful
      advancement of the midface ranging from 9 to 26 mm at the occlusal level as
      measured by preoperative and postoperative cephalograms was undergone by all
      patients. Advantages and disadvantages of the respective distraction systems are
      reviewed to better understand unique patient characteristics leading to the
      successful use of these devices for correction of severe midface hypoplasia.

PMID- 11994577
TI  - Effect of distraction osteogenesis of the mandible on upper airway volume and
      resistance in children with micrognathia.
AB  - Children with craniofacial anomalies often have compromise of the upper airway, a
      condition with potential for morbidity and mortality. In children with
      microretrognathia, the diminutive size and retruded position of the mandible
      reduces the size of the oropharynx, thereby predisposing to glossoptosis and
      airway obstruction. Although several authors have reported successful use of
      mandibular distraction osteogenesis to alleviate this type of upper airway
      obstruction, the physiologic relationship between changes in mandibular shape,
      size, and position and upper airway dynamics remains undefined. The purpose of
      this study was to develop methodologies to quantitatively evaluate upper airway
      dynamics in children with micrognathia both before and after mandibular
      distraction osteogenesis. The patient population consisted of four children with
      micrognathia who had successfully undergone upper airway stabilization by
      bilateral mandibular distraction osteogenesis. The data used were digitally
      archived computed tomographic scan data from high-resolution, thin-slice head
      computed tomographic scans obtained before and after mandibular distraction.
      Upper airway evaluation was performed in two ways: static and dynamic. Static
      analysis consisted of computer quantification of predistraction and
      postdistraction mandibular and upper airway volumes using Analyze imaging
      software. Dynamic analysis consisted of fabrication of rigid stereolithographic
      hollow cast models of the upper airway produced from computed tomographic scan
      data. Models were used for characterization of upper airway resistance and flow
      patterns as related to respiration. After distraction osteogenesis, mandibular
      total volume increased 32, 32, 18, and 25 percent (mean, 27 percent) and upper
      airway volume increased by 20, 31, 23, and 71 percent (mean, 37 percent). A
      significant decrease in flow resistance, both inspiratory and expiratory, was
      observed in the patient with the greatest upper airway volume increase (71
      percent) after distraction. After distraction, the inspiratory resistance was
      diminished by 51 percent and the expiratory resistance diminished by 85 percent.
      However, the three patients with more modest upper airway volume increases of 20
      to 31 percent demonstrated no statistically significant change in flow resistance
      after distraction. Results of this study support the conclusion that distraction
      osteogenesis of the micrognathic mandible increases the volume of the upper
      airway, roughly paralleling the increase in mandibular volume. In the
      biomechanical airway model studied, upper airway volume expansion has been shown
      to be able to decrease the flow resistance over the length of the airway,
      presumably secondary to an increase in the average cross-sectional area. The
      artificial rigidity of the stereolithographic "airway" compared with the
      elasticity of the human upper airway may account for the insensitivity of this
      model to smaller but clinically significant airway changes.

PMID- 11994578
TI  - Long-term outcome study of bilateral mandibular distraction: a comparison of
      Treacher Collins and Nager syndromes to other types of micrognathia.
AB  - A long-term follow-up study of patients who underwent bilateral mandibular
      distraction is presented, and the results of patients with Treacher Collins
      syndrome and Nager syndrome are compared with results for other forms of
      congenital micrognathia. It was hypothesized that the factors responsible for the
      predetermined, syndrome-specific shape of the mandible in patients with Treacher
      Collins and Nager syndromes would alter the long-term results of linear
      (uniplanar) distraction of the mandible. Thus, over time, the mandibles would
      remodel to preoperative form while maintaining the increase in volume. To
      investigate this hypothesis, all patients treated with bilateral mandibular
      distraction who had at least 1.5 years of follow-up, including satisfactory
      cephalometric examinations, were retrospectively reviewed. Two groups were
      identified. Group 1 (n = 6) were Treacher Collins and Nager syndrome patients
      (ages, 2 to 13 years; mean, 5.2 years) and group 2 (n = 6) included other forms
      of bilateral, congenital micrognathia (ages, 1.5 to 19 years; mean, 8.4 years).
      Serial cephalometric measurements were recorded before distraction, after
      distraction, and at least 18 months after distraction. Mandibular mean linear
      distraction distance (as recorded on the device) averaged 24.5 mm in group 1 and
      26.2 mm in group 2. In group 1, the antegonial angle (angle from the mandibular
      plane to the top of the antegonial notch) decreased after distraction by 3.8
      degrees, and the antegonial notch height was reduced by 1.6 mm. The posttreatment
      morphologic change was modified significantly over time, with a 3.7-degree
      increase of the antegonial angle and a 1.2-mm deepening of the antegonial notch.
      In group 2, the immediate reduction in height of the antegonial notching was
      subtler; however, long-term recurrence of the antegonial notching was also
      observed. At the end of distraction, the mean group 1 gonial angle became 8
      degrees more obtuse. In contrast, patients in group 2 developed a more acute
      angle (mean, 8 degrees). The mandibles of the Treacher Collins syndrome patients
      (group 1) maintained their more obtuse postdistraction gonial angle during the
      period of follow-up, whereas over time this change was reversed in group 2
      patients. In conclusion, experience with bilateral mandibular distraction has
      demonstrated that long-term determination of mandibular form is more complex than
      either the amount of distraction or the direction of the distraction vector. The
      underlying genotype and the musculoskeletal milieu must be taken into account
      when planning distraction, as these factors tend to remodel the mandible into its
      preoperative shape over time, despite the fact that the increased mandibular
      volume and projection are maintained.

PMID- 11994580
TI  - Microsurgical scalp reconstruction in the patient with cancer.
AB  - The literature regarding reconstruction of large scalp wounds with free tissue
      transfer consists mostly of case reports and small series, and none of the
      published reports focus on the particular problems of the oncology patient. Here
      the authors describe their experience with 37 flaps in 32 patients, all of whom
      required scalp reconstruction with free tissue transfer after tumor extirpation.
      Twenty-seven free flaps were performed at the time of the initial surgery and 10
      were performed after a prior reconstruction failed. The authors describe the
      characteristics of the patients and procedures, including tumor type, wound size
      and complexity, flaps and recipient vessels used, preoperative and postoperative
      radiation therapy, and complications. Most (72 percent) of the tumors were
      recurrent or persistent. The free tissue transfer was successful in all patients.
      There was a 59 percent overall complication rate with 32 percent of patients
      requiring a secondary surgical procedure. Most of the complications were wound
      healing complications. Although there were two cases of vein thrombosis, these
      were salvaged by revision, and no flaps were lost. Nine patients underwent
      postoperative radiation therapy that was well tolerated. Only four patients
      underwent cranioplasty at the time of the initial operation, and no secondary
      cranial reconstructions were performed. The authors conclude that preoperative
      and postoperative radiation therapies as well as the need for expedient tumor
      resection and immediate flap coverage are issues that make free tissue transfer
      attractive for the oncology patient who needs scalp reconstruction. Although the
      complication rate is relatively high and a significant percentage of patients
      require a secondary procedure, free flap coverage was efficacious for all
      patients in this group. Cranioplasty is not usually required but, if needed,
      alloplastic or autologous cranial reconstruction does not appreciably increase
      morbidity in the selected patient.

PMID- 11994581
TI  - Anatomy of the nasal cartilages of the unilateral complete cleft lip nose.
AB  - The purpose of this study was to disclose the relationship between the anomaly of
      the cartilaginous framework and the nasal deformity of cleft lip. The noses of
      six stillborn infants with unilateral complete cleft lip were carefully
      dissected. The size and weight of the lower lateral cartilages were measured to
      determine whether there was a significant difference between the normal and
      involved sides. The position of the nasal cartilages was observed, and the
      distance between them was measured to determine whether they were normal. The
      surgical dissection revealed that the lower lateral cartilages from both sides
      were asymmetrical in three dimensions, indicating the displacement of the lower
      lateral cartilage on the involved side. There was displacement of the
      cartilaginous septum and the upper lateral cartilage. The statistical evaluation
      did not demonstrate a significant difference between weight and size of the two
      sides. One of the major causative factors of nasal deformity is displacement of
      the nasal cartilages. There is no hypoplasia of nasal cartilage in newborn
      infants with cleft lip.

PMID- 11994582
TI  - A 10-year experience in nasal reconstruction with the three-stage forehead flap.
AB  - Because of its ideal color and texture, forehead skin is acknowledged as the best
      donor site with which to resurface the nose. However, all forehead flaps,
      regardless of their vascular pedicles, are thicker than normal nasal skin. Stiff
      and flat, they do not easily mold from a two-dimensional to a three-dimensional
      shape. Traditionally, the forehead is transferred in two stages. At the first
      stage, frontalis muscle and subcutaneous tissue are excised distally and the
      partially thinned flap is inset into the recipient site. At a second stage, 3
      weeks later, the pedicle is divided. However, such soft-tissue "thinning" is
      limited, incomplete, and piecemeal. Flap necrosis and contour irregularities are
      especially common in smokers and in major nasal reconstructions. To overcome
      these problems, the technique of forehead flap transfer was modified. An extra
      operation was added between transfer and division.At the first stage, a full
      thickness forehead flap is elevated with all its layers and is transposed without
      thinning except for the columellar inset. Primary cartilage grafts are placed if
      vascularized intranasal lining is present or restored. Importantly, at the first
      stage, skin grafts or a folded forehead flap can be used effectively for lining.
      A full-thickness skin graft will reliably survive when placed on a highly
      vascular bed. A full-thickness forehead flap can be folded to replace missing
      cover skin, with a distal extension, in continuity, to supply lining. At the
      second stage, 3 weeks later during an intermediate operation, the full-thickness
      forehead flap, now healed to its recipient bed, is physiologically delayed.
      Forehead skin with 3 to 4 mm of subcutaneous fat (nasal skin thickness) is
      elevated in the unscarred subcutaneous plane over the entire nasal inset, except
      for the columella. Skin grafts or folded flaps integrate into adjacent normal
      lining and can be completely separated from the overlying cover from which they
      were initially vascularized. If used, a folded forehead flap is incised free
      along the rim, completely separating the proximal cover flap from the distal
      lining extension. The underlying subcutaneous tissue, frontalis muscle, and any
      previously positioned cartilage grafts are now widely exposed, and excess soft
      tissue can be excised to carve an ideal subunit, rigid subsurface architecture.
      Previous primary cartilage grafts can be repositioned, sculpted, or augmented, if
      required. Delayed primary cartilage grafts can be placed to support lining
      created from a skin graft or a folded flap. The forehead cover skin (thin,
      supple, and conforming) is then replaced on the underlying rigid, recontoured,
      three-dimensional recipient bed. The pedicle is not transected. At a third stage,
      3 weeks later (6 weeks after the initial transfer), the pedicle is divided. Over
      10 years in 90 nasal reconstructions for partial and full-thickness defects, the
      three-stage forehead flap technique with an intermediate operation was used with
      primary and delayed primary grafts, and with intranasal lining flaps (n = 15),
      skin grafts (n = 11), folded forehead flaps (n = 3), turnover flaps (n = 5),
      prefabricated flaps (n = 4), and free flaps for lining (n = 2). Necrosis of the
      forehead flap did not occur. Late revisions were not required or were minor in
      partial defects. In full-thickness defects, a major revision and more than two
      minor revisions were performed in less than 5 percent of patients. Overall, the
      aesthetic results approached normal. The planned three-stage forehead flap
      technique of nasal repair with an intermediate operation (1) transfers subtle,
      conforming forehead skin of ideal thinness for cover, with little risk of
      necrosis; (2) uses primary and delayed primary grafts and permits modification of
      initial cartilage grafts to correct failures of design, malposition, or scar
      contraction before flap division; (3) creates an ideal, rigid subsurface
      framework of hard and soft tissue that is reflected through overlying skin and
      blends well into adjacent recipient tissues; (4) expands the application of
      lining techniques to include the use of skin grafts for lining at the first
      stage, or as a "salvage procedure" during the second stage, and also permits the
      aesthetic use of folded forehead flaps for lining; (5) ensures maximal blood
      supply and vascular safety to all nasal layers; (6) provides the surgeon with
      options to salvage reconstructive catastrophes; (7) improves the aesthetic result
      while decreasing the number and difficulty of revision operations and overall
      time for repair; and (8) emphasizes the interdependence of anatomy (cover,
      lining, and support) and provides insight into the nature of wound injury and
      repair in nasal reconstruction.

PMID- 11994584
TI  - The temporalis: blood supply and innervation.
AB  - Numerous reports have described the use of the temporalis muscle as a pedicled
      flap in reconstructive surgery. A detailed knowledge of the supplying vessels and
      nerves is necessary for functionally successful muscle transposition. However,
      controversial anatomic descriptions exist. In this study, 60 human cadavers were
      investigated to identify the arteries and nerves supplying the temporalis. Forty
      three cadavers were dissected after embalming with 10% phenol/formaldehyde. An
      additional 10 cadavers were examined after injecting latex/barium sulfate (ratio,
      1:1) to show the parts of the temporalis supplied by each artery using
      radiography. The innervating motor branches of the trigeminal nerve were
      identified by the Karnovsky technique in seven fresh cadavers. In all specimens,
      three arteries supplying the temporalis were identified: the anterior deep
      temporal artery (anterior part, 30 percent muscle mass), the posterior deep
      temporal artery (central part, 51 percent muscle mass), and the medial temporal
      artery (occipital and in 25 percent upper part, 19 percent muscle mass). Motor
      branches of the trigeminal nerve innervated the temporalis: the deep temporal
      nerves of the mandibular nerve (98 percent, central part), branches of the buccal
      nerve (95 percent, anterior part), and branches of the masseteric nerve (69
      percent, posterior part). A remarkable variation of innervating nerve branches,
      and in 12 percent peripheral anastomoses between the motor nerve branches, were
      observed. The various numbers of innervating nerve branches demonstrate the
      difficulty of creating innervated or selectively denervated pedicled muscle flaps
      for reinnervation. Nevertheless, at least two different pedicled flaps using the
      anterior or central part of the temporalis can be selectively used for
      reconstructive surgery.

PMID- 11994585
TI  - The new bilaterally pedicled V-Y advancement flap for face reconstruction.
AB  - A new bilaterally pedicled V-Y advancement flap based on two subcutaneous
      pedicles that vascularize the skin island through subdermal plexus lateral
      bridges is described for face reconstruction. It differs from traditional V-Y
      advancement flaps in that it does not rely on the classic subcutaneous "vertical"
      pedicle that is sectioned from top to bottom to improve advancement of the skin
      island. This technique had predictable results for 12 years in 425 consecutive
      patients, with infection occurring in 2.8 percent of the cases and complete
      necrosis in less than 1 percent of the flaps.

PMID- 11994586
TI  - Osteoradionecrosis of the mandible after oromandibular cancer surgery.
AB  - Although postoperative radiotherapy has proved effective in improving local
      control and survival in patients with head and neck cancers, its complications,
      especially mandibular osteoradionecrosis, reduce the quality of life. Mandibular
      surgery before the radiotherapy adds an additional risk factor for
      osteoradionecrosis. This study reviews patients in Chang Gung Memorial Hospital,
      Taipei, Taiwan, over a 10-year period, who underwent intraoral cancer resection
      followed by postoperative radiotherapy and thereafter developed
      osteoradionecrosis of the mandible. A total of 24 men and three women with a mean
      age of 49.9 years were identified and included in the study. In 10 cases, tumor
      resection was performed with a marginal mandibulectomy; in eight cases, tumor
      resection was performed after mandibular osteotomy; and in three cases, a
      segmental mandibulectomy was performed, and the defect was reconstructed with a
      fibula osteoseptocutaneous flap. In six cases, tumor excisions were performed
      without interfering with the mandibular continuity. Patients received
      postoperative external beam radiotherapy into the primary site and the neck, with
      a mean dose (+/-SD) of 5900 +/- 1300 cGy in an average of 35 fractions during an
      average of 6.5 weeks. The average elapsed time between the end of radiation
      therapy and clinical diagnosis of osteoradionecrosis of the mandible was 11.2
      months (range, 2 to 36 months). The time elapse between the end of the radiation
      therapy and the diagnosis of osteoradionecrosis was influenced by initial
      treatment (Kruskal-Wallis test: n = 27, chi-square = 12.884, p < 0.005), and this
      period was shorter if the mandibular osteotomy or marginal mandibulectomy was
      performed (the two lowest mean ranks in the test). However, if the initial
      surgery resulted in a segmental mandibulectomy reconstructed with a fibula
      osteoseptocutaneous flap, onset of the osteoradionecrosis was relatively late
      (Kruskal-Wallis test: n = 21, chi-square = 7.731, p = 0.052). After resection of
      osteoradionecrotic bone and surrounding soft tissue, 22 patients underwent
      reconstructive procedures with a fibula osteoseptocutaneous flap, and five
      patients underwent reconstructive procedures with an inferior genicular artery
      osteoperiosteal cutaneous flap. One fibula osteoseptocutaneous flap showed total
      failure and another showed a 25 percent skin loss; both were revised with
      pedicled flaps. The skin paddle of an inferior genicular artery flap was replaced
      with an anterolateral thigh flap because of anatomic variation of the skin
      vessel. Once the diagnosis of osteoradionecrosis is established, replacement of
      the dead bone and surrounding tissue with a vascularized free bone flap is
      inevitable, and a composite osteocutaneous free flap is a good option.

PMID- 11994587
TI  - A retrospective analysis of 48 infected sternal wound closures: delayed closure
      decreases wound complications.
AB  - Forty-eight patients who suffered sternal wound infections following coronary
      artery bypass grafting were retrospectively reviewed over a 5-year period. All
      patients in this study had clinical signs of major infection including redness,
      pain, and purulence at the time of mediastinal drainage and debridement. One
      patient died 11 days postoperatively because of heart failure, leaving 47
      patients available for long-term follow-up. All muscle flaps (pectoralis and
      rectus abdominis) survived completely. All wound complications were related to
      chest wall skin flap dehiscence or continued infection. Seventeen of 22 patients
      (77 percent) undergoing flap closure 4 days or less after sternal debridement and
      irrigation suffered wound complications. Five of these 22 patients (23 percent)
      had major wound complications, meaning that the wound required more than 2 months
      of care before healing was complete. No major wound complications and only three
      minor complications (12 percent) occurred in 25 patients undergoing sternal flap
      closure 5 days or more after mediastinal debridement and irrigation. The
      frequency and severity of wound complications were significantly decreased in the
      group of patients undergoing sternal flap closure 5 or more days after sternal
      drainage and debridement (p < 0.00005). In the majority of cases [29 of 47 (62
      percent)], secure sternal wound closure was obtained with a single, split,
      medially based, right pectoralis major muscle flap.

PMID- 11994589
TI  - Implications of axillary sentinel lymph node biopsy in immediate autologous
      breast reconstruction.
AB  - For patients with invasive breast cancer, if the results of an axillary sentinel
      node biopsy are determined to be positive after permanent pathologic examination,
      the current recommendation is to perform a complete axillary node dissection.
      Subsequent axillary surgery may compromise the blood supply to an immediate
      autologous breast reconstruction. The purpose of this study was to determine
      which clinicopathologic factors in clinically node-negative breast cancer
      patients may be associated with an increased risk of positive axillary nodes.
      Identification of these factors will allow surgeons to modify their approach to
      immediate autologous breast reconstruction in these high-risk patients. The
      relationship between presenting clinicopathologic characteristics and the
      incidence of axillary metastases was analyzed by chi-square test and multivariate
      analysis in 167 patients with invasive breast cancer and a clinically negative
      axilla who underwent modified radical mastectomy with an immediate free
      transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction. Axillary
      nodal metastases were found in 35 percent of clinically node-negative breast
      cancer patients. Multivariate analysis showed that patient age of 50 years or
      younger (p = 0.019), T2 tumor stage or greater (p = 0.031), and presence of
      lymphovascular invasion on the initial biopsy specimen (p < 0.001) were
      independent predictors of axillary metastases in clinically node-negative
      patients. Based on these results, the authors propose an algorithm for decision
      making in clinically node-negative breast cancer patients who desire autologous
      breast reconstruction and sentinel lymph node biopsy. Options for immediate
      autologous breast reconstruction in patients undergoing mastectomy and axillary
      sentinel lymph node biopsy that may minimize the risk of vascular damage on
      reoperation include the use of the internal mammary artery and vein as recipient
      vessels for a free TRAM flap or a pedicled TRAM flap. If an axillary-based blood
      supply is used, the authors are considering the use of cadaveric dermis to
      isolate the pedicle of the flap away from the remaining axillary contents. New
      developments in breast cancer diagnosis and treatment necessitate a team
      approach, with increased communication between the breast surgeon and the plastic
      surgeon in planning surgery for these patients.

PMID- 11994590
TI  - Breast reconstruction using the sensate latissimus dorsi musculocutaneous flap.
AB  - The authors performed immediate breast reconstruction on four patients using a
      sensate latissimus dorsi musculocutaneous flap accompanied by neurorrhaphy during
      the past 6 years. In the neurorrhaphy, the lateral cutaneous branch of the dorsal
      primary divisions of the seventh thoracic nerve, which controls the sensation of
      the myocutaneous flap, was anastomosed to the lateral cutaneous branch of the
      fourth intercostal nerve, which controls the sensation of the breast. The
      subjects consisted of four patients whose postoperative follow-up period was 14
      to 29 months, with an average of 19.3 months. The control subjects consisted of
      10 cases with a latissimus dorsi musculocutaneous flap whose sensory nerve had
      not been reconstructed (postoperative follow-up period, 15 to 49 months; average,
      26.9 months). The sensory examination included tests of touch, pain, and
      temperature. The innervated musculocutaneous flap sensation showed gradual
      recovery at about 6 months after surgery and reached the value of the normal side
      after about 1 year. In the control subjects, the recovery was gradual after more
      than 1 year and reached the value of the normal side in only some of the control
      subjects. On the basis of these findings, the authors consider the present
      technique to be useful for the recovery of sensation in immediate breast
      reconstruction.

PMID- 11994592
TI  - Donor site sequelae after autologous breast reconstruction with an extended
      latissimus dorsi flap.
AB  - The indications for autologous reconstruction are increasing. The standard
      procedure is the transverse rectus abdominis muscle flap; however, this flap has
      contraindications and drawbacks. The latissimus dorsi muscle flap is simple and
      reliable. Hokin et al. demonstrated in 1983 that this flap can be extended and
      used for breast reconstruction without an implant. Since then, it has been widely
      studied in this setting and is known to provide good aesthetic results. Dorsal
      sequelae, conversely, were not appraised. The aim of this study was to assess
      objective and subjective dorsal sequelae after the harvest of an extended flap.
      Forty-three consecutive patients who had had breast reconstruction with an
      autologous latissimus dorsi flap were assessed by a surgeon and a physiotherapist
      for muscular strength and shoulder mobility. Patient opinion was studied through
      a questionnaire. Mean delay between the operation and the evaluation was 19
      months. Early complications, mainly dorsal seromas, were frequent after the
      harvest of an extended flap (72 percent). There was no late morbidity and,
      especially, no flap loss or partial necrosis. As for functional results, 37
      percent of the patients had complete adjustment and 70 to 87 percent demonstrated
      no change in shoulder strength. Sixty percent of the patients experienced no
      limitation in everyday life, and 90 percent said they would undergo this
      procedure again. The authors show that dorsal sequelae after an extended
      latissimus dorsi flap are minimal and that this technique compares favorably with
      the transverse rectus abdominis muscle flap.

PMID- 11994593
TI  - Perforator topography of the deep inferior epigastric perforator flap in 100
      cases of breast reconstruction.
AB  - The anatomic topography of the perforators within the rectus muscle and the
      anterior fascia largely determines the time needed to harvest the perforator free
      flap and the difficulty of the procedure. In 100 consecutive cases, the
      topographic patterns of the perforators were investigated. In 65 percent, a short
      intramuscular course was seen. In 16 percent, a perforator at the tendinous
      intersection was encountered. In 9 percent, the largest perforator was found to
      have a long intramuscular course. In 5 percent, a subfascial course was found,
      and in another 5 percent, a paramedian course was found. In 74 percent of flaps,
      just one perforator was used, whereas two perforators were dissected in 20
      percent. Only in 6 percent of flaps were three perforators used. A long
      intramuscular course (>4 cm) lengthens the dissection substantially, especially
      when the intramuscular course is in a step-wise pattern. The subfascial course
      requires precarious attention at the early stage of the perforator dissection
      when splitting the fascia. The perforators at the tendinous intersections are the
      most accessible and require a short but intense dissection in the fibrotic tissue
      of intersection. A paramedian perforator, medial to the rectus muscle, is a
      septocutaneous rather than a musculocutaneous perforator. The straightforward
      dissection almost extends up to the midline. Therefore, dissection always is
      performed at one side and, if no good perforators are present, continued at the
      intact contralateral side. The size of these perforators and their location in
      the flap determine the choice. One perforator with significant flow can perfuse
      the whole flap. If in doubt, two perforators can be harvested, especially if they
      show a linear anatomy so that muscle fibers can be split. The only interference
      with the muscle exists in splitting the muscle fibers. A perforator that lies in
      the middle of the flap is preferable. For a large flap, a perforator of the
      medial row provides better perfusion to zone 4 than one of the lateral row
      because of the extra choke vessel for the lateral row perforators. The clinical
      appearance of the perforators is the key element in the dissection of the
      perforator flap. Perforator topography determines the overall length and
      difficulty of the procedure.

PMID- 11994594
TI  - Radiation effects on breast reconstruction with the deep inferior epigastric
      perforator flap.
AB  - Immediate breast reconstruction has important advantages over delayed
      reconstruction, including a shorter operative time and decreased psychological
      distress for the patient. However, the authors' experiences with the deep
      inferior epigastric perforator flap demonstrate variable aesthetic outcomes among
      patients who undergo radiation postoperatively. To establish an association
      between radiation and poor postoperative results, a matched-pairs analysis was
      conducted. Thirty irradiated patients were paired with 30 nonirradiated patients,
      according to age and body mass index. For each group, the incidence of fat
      necrosis, fibrosis/shrinkage, and flap contracture was recorded. In addition, an
      aesthetic evaluation was conducted to compare before-and-after images of 10
      irradiated patients with those of 10 nonirradiated patients from similar time
      periods. The images were randomized and blindly evaluated by a panel of eight
      judges. A five-point scale was used to evaluate symmetry, aesthetic proportion,
      and the appearance of the superior pole. Statistical analysis demonstrated a
      significant difference in the score changes for irradiated and nonirradiated
      patients, according to all three criteria. Nonirradiated patient scores increased
      by one-half point, and irradiated patient scores decreased by one-half point. In
      addition, the incidences of fat necrosis, fibrosis, and flap contracture were all
      significantly higher among the irradiated group. These results suggest that when
      possible, reconstruction should be delayed until after radiation therapy is
      complete. Persons who smoke or are obese may be at particular risk for
      complications following radiation therapy.

PMID- 11994596
TI  - In vivo aging characteristics of silicone gel breast implants compared to lot
      matched controls.
AB  - A study was conducted to investigate the effect of in vivo aging on the physical,
      mechanical, and chemical properties of Silastic II gel-filled breast implants. In
      the study, the properties of 16 Silastic II gel-filled explants (retrieved from
      eight patients), with in vivo duration times ranging from 4 months to 13 years,
      were compared with lot-matched control (unimplanted) samples. Tensile and tear
      strength properties were measured for both explant and control shells by using
      identical testing protocols. The tensile strength properties of shells, which
      were extracted with hexane to remove non-cross-linked silicones, were also
      measured. Swelling measurements were used to determine the average molecular
      weight between cross-links (or entanglements). In addition, scanning electron
      microscopy was applied in the comparison of the morphological features of the
      explants and their lot-matched controls. The results of the study suggest that
      the silicone polymer used to fabricate the shells does not undergo appreciable
      degradation for up to 13 years in vivo. The study represents an investigation of
      the world's largest known inventory of explanted breast implants with lot-matched
      controls.

PMID- 11994597
TI  - Surgical strategy for improving forearm and hand function in late obstetric
      brachial plexus palsy.
AB  - For the purpose of treatment, obstetric brachial plexus palsy can be subdivided
      into two distinct phases: initial obstetric brachial plexus palsy, and late
      obstetric brachial plexus palsy. In the latter, nerve surgery is no longer
      practical, and treatment often requires palliative surgery to improve function of
      the shoulder, elbow, forearm, and hand. Late obstetric brachial plexus palsy in
      the forearm and hand includes weakness or absence of wrist or metacarpophalangeal
      or interphalangeal joint extension; weakness or absence of finger flexion;
      forearm supination, or less commonly pronation contracture; ulnar deviation of
      the wrist; dislocation of the radial or ulnar head; thumb instability; or sensory
      disturbance of the hand. Palliative reconstruction for these forearm and hand
      manifestations is more difficult than for the shoulder or elbow because of the
      lack of powerful regional muscles for transfer. This report reviews the authors'
      experience performing more than 100 surgical procedures in 54 patients over a 9
      year period (between 1988 and 1997) with a minimum of 2 years' follow-up.
      Surgical treatment is highly individualized, but the optimal age for forearm and
      hand reconstruction is usually later than for shoulder and elbow reconstruction
      because of the requirement for a preoperative exercise program. Multiple
      procedures for forearm and hand function were often performed on any given
      patient. Frequently, these were done simultaneously with reconstructive
      procedures for improving shoulder and/or elbow function. Traditional tendon
      transfer techniques do not provide satisfactory reconstruction for those
      deformities. Many of the authors' patients required more complex techniques such
      as nerve transfer and functioning free-muscle transplantation to augment
      traditional techniques of tendon and/or bone management. Sensory disturbance of
      the forearm and hand in late obstetric brachial plexus palsy seems a minor
      problem and further sensory reconstruction is unnecessary.

PMID- 11994598
TI  - The "beggar's" hand and the "unshakable" hand in children with total obstetric
      brachial plexus palsy.
AB  - A total 12 consecutive children with secondary deformities following total
      obstetric brachial plexus palsy were included in this retrospective study. In all
      patients, the main complaints were two socially disabling hand postures: the
      "beggar's" hand and/or the "unshakable" hand. All children had a supinated
      forearm with no active pronation and were teased by their friends, who called
      them "beggars." When the impairment was severe and involved the right hand and
      wrist, children also complained that they were not able to shake hands. The
      management approach to these children was described, with the main aim of surgery
      being the correction of the abnormal posture. Other simultaneous tendon transfers
      were also performed to improve hand function if there were suitable
      musculotendinous units. Successful reconstruction was accomplished in all
      patients. Preoperatively, some children refused to go to school because of
      teasing, and most did not want to interact socially. After surgery, all children
      attended school regularly, and parents reported much better social interaction.
      However, the functional gain was never enough to dramatically improve the daily
      use of the limb. The contralateral normal limb remained the dominant one for all
      daily activities, including writing and eating.

PMID- 11994599
TI  - Comparison of partial excision with simple section of the transverse carpal
      ligament in the treatment of carpal tunnel syndrome.
AB  - In the surgical treatment of carpal tunnel syndrome, debate has commonly focused
      on whether decompression should be performed by open or blind techniques.
      Contrarily, the goal of the present study was to determine whether instead of
      simple section, partial excision of the transverse carpal ligament has
      contributed to better results. Because complete healing of the transverse carpal
      ligament observed during reoperations has been reported elsewhere, the charts of
      75 carpal tunnel syndrome patients who had been treated with open technique at
      Dokuz Eylul University were reviewed. Statistical analysis was performed using
      the Fisher's exact test and Student's t test when appropriate. Thirty-five
      patients had been treated with simple section of the transverse carpal ligament,
      whereas 40 had been treated with partial excision. Internal neurolysis was also
      performed in 19 of the patients, 11 of whom were treated with partial excision.
      The average follow-up time was 3.8 years. The comparisons regarding the overall
      operative outcomes did not show any significant difference between the two
      different techniques of releasing the transverse carpal ligament. In patients
      treated without neurolysis, results of partial excision of the transverse carpal
      ligament improved when compared with those of simple section, but this
      superiority was not statistically significant. There seemed to be statistically
      higher reoperation rates and worse outcomes after neurolysis (p < 0.05).
      Reoperation was required in eight patients (11 percent). Five of the patients who
      underwent reoperation had initially been treated with partial excision and
      neurolysis, whereas two had been treated with simple section and neurolysis.
      Another patient who had undergone reoperation had initially undergone only simple
      section. The mean time to return to work or daily activities did not differ
      between the types of applied technique for releasing the transverse carpal
      ligament. However, neurolysis lengthened these periods significantly when
      performed (p < 0.05). In the present study, partial excision of the transverse
      carpal ligament without adding neurolysis offered relatively better results than
      simple section. Verification of this finding endoscopically, if applicable, may
      improve the success rate of surgical therapy in patients with carpal tunnel
      syndrome.

PMID- 11994600
TI  - The free latissimus dorsi flap revisited: a primary option for coverage of wide
      recurrent lumbosacral defects.
AB  - In comparison with other regions of the trunk, defects located in the lumbosacral
      region are infrequent. However, these particular lesions sometimes present
      difficulties in reconstruction, arising from the quality of the surrounding
      tissue and the width of the defects. In this area, the skin adheres strongly to
      subcutaneous tissue and is difficult to mobilize. Attempts to perform local or
      regional flaps for covering defects of this area often end in necrosis of the
      flaps, with subsequent risk of infection and unstable wounds. The consequence is
      larger defects and the need for a wide, tension-free coverage, which can be
      performed after a wide debridement. The authors report on 10 patients presenting
      with wide, recurrent (and in some cases, infected) defects of the lumbosacral
      region, after already having undergone several reconstructive local or regional
      operations. In all cases, the authors harvested a free latissimus dorsi flap,
      lengthening the pedicle by means of an arteriovenous suralis loop connected to
      the thoracodorsal vessels (lumbar defect) or the femoral vessels (sacral defect).
      The procedure, already described in the past by others, has been revisited by the
      authors' group and used as the technique of choice in selected cases, that is, in
      the presence of wide, recurrent, and infected lesions; radiation; and scarring
      injuries. The authors thus obtained stable coverage with well-vascularized tissue
      and were able to save the patients any further operations. The authors suggest,
      therefore, that this procedure can be used in cases of wide and recurrent defects
      where other conventional procedures have failed. Advantages, disadvantages, and
      technical features of the method used are discussed in this article.

PMID- 11994601
TI  - Role of BMP, betaig-h3, and chitosan in early bony consolidation in distraction
      osteogenesis in a dog model.
AB  - The purpose of this investigation was to study the effect of bone morphogenetic
      protein (BMP), transforming growth factor beta-induced gene h3 (betaig-h3), and
      chitosan on early bony consolidation in distraction osteogenesis in a dog model.
      Sixteen dogs were used for this study. The lateral surface of the mandibular body
      was exposed in the subperiosteal plane and the vertical osteotomy on the
      mandibular body was extended downward. An external distraction device was applied
      to the mandibular body, and the mandibular distraction was started 5 days after
      the operation at a rate of 2 mm/day up to a 10-mm distraction after 5 days. The
      experimental group was then divided into a control group, a BMP group, a betaig
      h3 group, and a chitosan group, depending on the type of implantation material
      used in the distracted area. On the same day after completing the distraction,
      BMP, betaig-h3, or chitosan was implanted into the distracted area. No material
      was implanted into the distracted area in the control group. After implanting the
      materials, the distraction device was left in place for 7 weeks to allow for bony
      consolidation. Four dogs were allocated to each group. Two dogs in each group, a
      total of eight dogs, were killed 4 weeks after completing the distraction and the
      other eight dogs were killed after 7 weeks. Serial radiographs were obtained
      every week after completing the distraction. New bone was generated in the
      distracted zone in all groups. In the BMP group, the formation of active woven
      bone was observed throughout the distracted zone, and the new bone appeared to be
      nearly normal cortical bone 7 weeks after implantation. In the betaig-h3 and
      chitosan groups, the development of new bone was observed in the distracted zone
      after 7 weeks; however, the amount was less than that in the BMP group. In the
      control group, the new bone was observed at the edges of the distracted zone.
      These findings suggest that BMP seems to be very effective in early bony
      consolidation in distraction osteogenesis.

PMID- 11994602
TI  - Easy tissue expansion of prelaminated mucosa-lined flaps for cheek reconstruction
      in a canine model.
AB  - In head and neck reconstruction, there is sometimes the need for a skin flap
      lined with mucosa. The object of this study was to determine whether small pieces
      of mucosa grafted onto the undersurface of a skin flap can be expanded in a
      reasonable time to provide the material required to reconstruct a full-thickness
      cheek defect as a free flap. The study consisted of two phases: prelamination and
      expansion of the flap, and vascularized free-tissue transfer of the flap. Six
      adult mongrel dogs were used. First, a 5 x 10-cm flap based on the saphenous
      vessels was elevated on the lower leg, and then four 1 x 2-cm pieces of mucosa
      harvested from the tongue were grafted onto the undersurface of the flap. A
      tissue expander (5 x 10 cm) was then placed under the flap, and the incision was
      closed primarily. The expanders were initially filled with just enough normal
      saline to obliterate dead space immediately after surgery. The expansion was
      continued twice weekly for 3 weeks until sufficient expansion was obtained. Two
      of six flaps were followed for an additional 6 weeks after the 3-week expansion
      period to observe whether additional mucosa could be obtained. After measurement
      of the mucosal area, each flap was transferred as free flap to reconstruct an
      iatrogenic cheek defect. The increase of mucosal surface area was compared with
      the original graft, and differences were analyzed using the paired t test. All
      flaps were successfully expanded without any complications. Histologic evaluation
      revealed that grafted mucosa took well without evidence of graft necrosis, and
      the intergraft area was covered with histiocytes. Angiography revealed well
      defined vascular structures covering the entire area of the flap. The new mucosal
      area (23.5 +/- 2.4 cm2) was significantly larger than the original mucosal graft
      (8.7 +/- 0.9 cm2) (p < 0.001). The net increase of the mucosal area was 172.9 +/-
      32.4 percent. The increase of mucosal area in two flaps, following a 6-week
      consolidation period after 3 weeks of expansion, was only slightly greater (25.9
      +/- 1.3 cm2) than those without the consolidation period (22.3 +/- 1.8 cm2). This
      increase of the mucosal area appears to be related to the amount of expansion,
      and not to the length of the consolidation period. The flaps were successfully
      transferred as free flaps to reconstruct the full-thickness cheek defects without
      major complications. Although a staged operation to allow flaps to mature is
      needed, the present procedure has the advantages of providing a mucosa-lined flap
      and allowing primary closure of the donor site. The authors conclude that
      expansion of this flap has great potential in reconstructive surgery.

PMID- 11994603
TI  - Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene
      therapy.
AB  - A novel approach to treat ischemic tissues by using gene therapy has recently
      been introduced on the basis of the angiogenic potential of certain growth
      factors. The authors investigated the effect of adenovirus-mediated gene therapy
      with vascular endothelial growth factor (VEGF) delivered into the subdermal space
      to treat compromised skin flaps. For this purpose, the epigastric skin flap model
      in rats, based solely on the right inferior epigastric vessels, was used. Thirty
      male Sprague-Dawley rats were divided into five groups of six rats each. Viral
      transfection with 108 plaque-forming units was performed 2 days before the
      epigastric flap elevation. Rats received subdermal injections of adenovirus
      encoding VEGF (Ad-VEGF) or green fluorescent protein (Ad-GFP) as treatment
      control. Another set of animals (n = 6) received no injections and were
      designated as control. To determine whether site of injection had an impact on
      flap viability, injections were given into the predicted local ischemic area (Ad
      VEGF local, n = 6; Ad-GFP local, n = 6) and into the midline of the flap (Ad-VEGF
      midline, n = 6; Ad-GFP midline, n = 6). A flap measuring 8 x 8 cm was outlined on
      the abdominal skin extending from the xiphoid process proximally and the pubic
      region distally, to the anterior axillary lines bilaterally. Then, the epigastric
      flap was elevated as an island on the right inferior epigastric vessels and
      sutured back to its bed. Flap viability was evaluated at 7 and 14 days after the
      first operation. The epigastric flaps were scanned to the computer and areas of
      hypoxic and/or necrotic zones relative to total flap surface area were measured
      and expressed as percentages by using Image Pro Plus software. Specimens were
      taken for histologic evaluation at day 14 before the animals were killed.
      Combined area of necrotic and hypoxic zones as well as necrotic zone were
      decreased to 9.7 +/- 1.4 percent and 1.4 +/- 0.9 percent in Ad-VEGF local, and
      11.8 +/- 1.9 percent and 3.5 +/- 1.64 percent in Ad-VEGF midline compared with
      the control and Ad-GFP treatment groups (control, 23 +/- 3.6 percent and 20.1 +/-
      3.3 percent; Ad-GFP local, 24.8 +/- 4.8 percent and 16.2 +/- 5.9 percent; and Ad
      GFP midline, 23.4 +/- 6.9 percent and 19.5 +/- 7.7 percent; p < 0.05). Histologic
      evaluation by light microscopy failed to demonstrate any quantitative difference
      in vascularity of skin flaps between the treatment groups. In this study, the
      authors demonstrated that adenovirus-mediated gene therapy using VEGF enhanced
      epigastric skin flap survival, as confirmed by the significant reduction in
      combined area of necrotic and hypoxic zones of the flap. Compared with the
      control, both local and midline subdermal injections of Ad-VEGF showed
      improvement in overall flap survival by 57.9 and 48.7 percent, respectively. The
      results of this study raise the possibility of using adenovirus-mediated
      therapeutic angiogenesis for safer flap surgery in high-risk patients.

PMID- 11994604
TI  - The effect of low-molecular-weight heparin in the survival of a rabbit congested
      skin flap.
AB  - Swelling and congestion of flaps are frequently seen postoperatively and can
      cause unexpected necrosis. According to previous reports, venous thrombosis seems
      to be a more frequent problem than arterial occlusion in both experimental and
      clinical surgery. Few satisfactory venous trauma models exist, and reports on
      experimental venous thrombosis are rare. The object of this study was to create a
      rabbit venous occlusion flap model and to evaluate the effect of low-molecular
      weight heparin on this flap. Eight New Zealand rabbits were used in the pilot
      study, in which the ideal congested flap was investigated using a flap pedicle
      based on the central auricular artery with a skin pedicle 0, 1, 2, or 3 cm wide.
      The flap (3 x 6 cm) was designed on the central part of the left ear, and the
      central auricular vein and nerve, the former for venous return, were cut out at
      the base of the flap. The flaps with skin pedicles 0, 1, 2, or 3 cm wide showed
      mean necrosis length of 60.0, 9.3, 4.2, and 0.0 mm, respectively. The flaps with
      skin pedicles 0, 1, 2, or 3 cm wide showed mean necrosis of 100, 15.5, 7, and 0
      percent, respectively. Therefore, the flap, based on a 1-cm-wide skin pedicle and
      the central auricular artery, was selected as an optimal congested flap model
      showing 15.5 percent necrosis. The congested flap was then elevated on the left
      ear of another 10 rabbits. Subcutaneous low-molecular-weight heparin (320 IU/kg)
      was administered immediately after surgery to five of the rabbits (the low
      molecular-weight heparin group), and the remaining five were used as a control
      group. Fluorescein was injected 15 minutes after surgery to evaluate the
      circulatory territory of the flap, and the circulatory territory was measured 5
      minutes after injection. The flaps were assessed 7 days after surgery by
      angiography, histology, and clinical findings. The circulatory territory was
      significantly greater in the low-molecular-weight heparin group (mean +/- SD,
      39.2 +/- 3.0 mm) than the control group (mean +/- SD, 48.0 +/- 1.0 mm) (p <
      0.001) assessed 7 days after surgery. The longest flap survival length in group A
      and group B ranged from 40 to 55 mm (mean +/- SD. 49.4 +/- 5.6 mm) and complete
      survival (mean +/- SD, 60.0 +/- 0.0 mm). The improvement in survival was
      statistically significant for group B compared with group A (p < 0.015).
      Histologic evaluation revealed moderate to severe venous congestion and
      inflammation in the control group, whereas there were minimal changes in the low
      molecular-weight heparin group. Angiography of the flap revealed obvious venous
      occlusion in the periphery in the control group compared with the low-molecular
      weight heparin group. The authors conclude that subcutaneous administration of
      low-molecular-weight heparin has a great potential to improve the survival length
      of a congested flap without major complications.

PMID- 11994605
TI  - Dapsone for the treatment of doxorubicin extravasation injury in the rat.
AB  - Doxorubicin is the most common antitumor drug implicated in serious extravasation
      injuries. Progressive tissue necrosis may lead to intense pain, chronic
      ulceration, and disfiguring tissue loss. This progressive necrosis is analogous
      to that seen with brown recluse spider bites, where dapsone is an established
      mode of therapy, minimizing the area of tissue loss by a proposed
      antiinflammatory mechanism. The backs of 50 Lewis rats were injected
      intradermally with 1 mg of doxorubicin in 1 cc of saline to simulate an
      extravasation injury. The rats were divided into five groups for treatment with
      oral dapsone 50 mg/kg/day: 10 were controls (no treatment), 10 were started the
      day before injury, 10 were started the day of injury, 10 were started the day
      after injury, and 10 were started 1 week after injury. The area of ulceration was
      calculated by planimetry. The data suggest that dapsone has little positive
      effect on healing extravasation ulcers.

PMID- 11994606
TI  - Laser Doppler perfusion imager use in incisional hernia repair following omental
      breast reconstruction.

PMID- 11994607
TI  - Hung span method of scaphocephaly reconstruction in patients with elevated
      intracranial pressure.

PMID- 11994608
TI  - Double U-plasty for correction of geometric malposition of the nipple-areola
      complex.

PMID- 11994609
TI  - VCS auto suture stapled microvascular anastomoses in lower leg free flaps.

PMID- 11994610
TI  - Using the extensor digitorum brevis muscle to improve donor-site morbidity of the
      dorsalis pedis flap.

PMID- 11994611
TI  - Pedicled osteocutaneous fibula flap for reconstruction in the lower extremity.

PMID- 11994612
TI  - An analysis of telephone interview data collected in 1992 from 820 women who
      reported problems with their breast implants to the food and drug administration.
AB  - How health care providers deal with concerns and feelings of women who have
      problems with their breast implants affects the women's satisfaction with their
      breast implants, yet in 1992 little was known about the concerns and feelings of
      these women. A qualitative analysis of in-depth telephone interviews conducted in
      1992 with 820 women from all regions of the United States who reported problems
      with their breast implants to the Food and Drug Administration and responded to
      an invitation to be interviewed provided data. Respondents were primarily 40 to
      69 years of age at the time of interview, Caucasian, married, and educated beyond
      high school. The sample was almost equally divided in reason for breast implants,
      with 65 percent being dissatisfied with their breast implants. Nearly all of the
      women had heard of problems with silicone gel-filled implants. Their main sources
      of information were television, newspapers, and magazines rather than their
      physicians or the breast implant manufacturers. Some women tried to avoid hearing
      the reports, and many tried to put the reported problems out of their minds.
      However, a majority (88.7 percent) wanted more information. The women expressed
      feelings of anger, regret, and worry, and repeatedly said they needed more
      information. Women who contacted the Food and Drug Administration about breast
      implant problems needed accurate and honest information from health care
      professionals. They wanted their physicians to explore their symptoms, fears, and
      concerns.

PMID- 11994613
TI  - Klippel-Trenaunay syndrome.
AB  - The association of three physical findings including capillary malformation,
      varicosities, and hypertrophy of bony and soft tissues corresponds to Klippel
      Trenaunay syndrome. This triad of findings, described by the two French
      physicians Klippel and Trenaunay in 1900, differs from Parkes-Weber syndrome, in
      that Klippel-Trenaunay syndrome does not incorporate significant hemodynamic
      arteriovenous fistulas. Generally, management of this disease process should be
      individualized. Surgery should be considered in cases where skin ulcerations lead
      to persisting and recurrent bleeding, or where digital deformities lead to
      functional disabilities or where significant limb overgrowth leads to both
      functional and psychological impairment. Persistent hematochezia, hematuria, and
      vaginal and esophageal bleeding are considered indications for surgical
      intervention. Recurrent attacks of thrombophlebitis and cellulitis are treated
      medically with antiinflammatory agents and antibiotics. Otherwise, management of
      this syndrome is generally conservative, consisting of psychological
      encouragement, reassurance, and the continued use of graduated compressive
      stockings for varicosities and intermittent pneumatic compression pumps for
      lymphatic edema.

PMID- 11994614
TI  - Duct tape and plastic surgery.

PMID- 11994615
TI  - Listen carefully, but adopt skeptically.

PMID- 11994616
TI  - Root z-epicanthoplasty in asian eyelids.
AB  - In the eyelids of Asians, the presence of epicanthal folds and the absence of
      supratarsal folds are a unique feature. The resulting appearance leads many to
      seek cosmetic improvement in the medial canthal area. Although many techniques
      have been described for the elimination of epicanthal folds, scarring and
      complexity in design are still barriers for surgeons to overcome. From July of
      1998 to May of 2000, the authors used root Z-epicanthoplasty on the eyelids of 30
      Asian patients to correct epicanthal folds. Results were satisfactory in all
      patients, with no complications. Root Z-epicanthoplasty, as performed by the
      authors, is a simple design and procedure; there is minimal scarring in the
      medial canthal area and no tension.

PMID- 11994618
TI  - Minimal access cranial suspension lift: a modified S-lift.
AB  - There is a strong trend at hand toward less dramatic facial rejuvenation surgery.
      Most of the authors' patients want a cosmetic improvement but not at the cost of
      prolonged disfigurement or a high risk of complications. In 1999, a very simple
      but effective rhytidectomy technique, termed an S-lift, was described in the
      literature and was adopted by the authors. Its basic principle is the suspension
      of sagging facial features by a strong, permanent purse-string suture. The
      procedure is performed with the patient under local anesthesia. Significant
      modifications were applied to the incision, to the purse-string suture anchoring
      site, and to the direction and shape of the skin excision. The authors named the
      modified procedure the minimal access cranial suspension lift to specifically
      describe the concept of the technique. Through an inverted L-shaped preauricular
      incision with extension below the sideburn, a limited skin undermining is
      performed. Two strong, permanent purse-string sutures are woven into the
      superficial musculoaponeurotic system tissues in a vertical U and an oblique O
      shape, initiating from a strong anchorage in the deep temporal fascia at the
      level of the helical crus. Tying these sutures produces a very powerful vertical
      correction of descended facial features that acts mainly on the jowls and the
      upper neck. The procedure can be extended by continuing the dissection over the
      malar fat pad, placing a third vertical purse-string suture with strong action on
      the nasolabial groove, and vertically repositioning the midfacial volumes. During
      20 months, pleasing results and a very low complication rate were obtained in 88
      consecutive patients with a mean age of 551/2 years. In this article, the authors
      provide a detailed description of the anesthetic and surgical technique, a
      demonstration of the results in different patient age categories, and a
      discussion comparing the minimal access cranial suspension lift with other types
      of facial rejuvenation procedures.

PMID- 11994619
TI  - Extended incision in open-approach rhinoplasty for asians.
AB  - The purpose of this study was to introduce an extended incision in open-approach
      rhinoplasty for obtaining greater satisfaction in aesthetic rhinoplasty for
      Asians. This incision is the same as for the usual open rhinoplasty incision, but
      it is extended along the caudal border of the footplates of the medial crura onto
      the floor of the nasal vestibule to access the footplates of the medial crura
      more easily. This simple extended incision enabled the authors to achieve further
      tip projection because the pressure of the skin flap on the tip was reduced. By
      approximating the lateral curves of the medial crural footplates, the width and
      the length of the columella were narrowed and lengthened, respectively. The
      columella was also advanced caudally; thus, the shape of the nostrils could also
      be elongated. In addition, a cartilage graft or an implant insertion for alar
      base augmentation could be performed through this extended incision without an
      additional incision. Another advantage was that in correction of caudal septal
      deviation, displaced septal cartilage could be repositioned by suturing to the
      periosteum or soft tissue around the anterior nasal spine without drilling into
      it through an intraoral incision. Fifty-one consecutive patients who underwent
      this extended open-approach rhinoplasty between August of 1999 and September of
      2000 were included in this study. A total of 40 patients had an adequate follow
      up time of over 6 months. Patient satisfaction and postoperative complications
      were recorded. The majority of the patients (35 of 40) were satisfied with the
      results of the procedure. Two patients had complications of nostril-scar
      contracture requiring close follow-up. There were no cases of implant extrusion,
      displacement, or infection. No patients experienced transcolumellar or extended
      incision scarring. Although further studies and longer follow-up are needed to
      determine the value of this incision, the authors believe that the addition of
      the extended incision in open-approach rhinoplasty is safe and reliable for
      effecting better results for Asians.

PMID- 11994620
TI  - Differing characteristics in 100 consecutive secondary rhinoplasty patients
      following closed versus open surgical approaches.
AB  - Open rhinoplasty has unquestionably become more popular during the past two
      decades because of the putative diagnostic and technical advantages that direct
      transcolumellar access offers. To test the hypothesis that patients initially
      treated by the opened or closed approaches differed in the secondary deformities
      that developed, a retrospective study was conducted of 100 consecutive secondary
      rhinoplasty patients (66 women and 34 men) operated on by the author before
      February of 1998. Sixty-four percent had previously undergone closed
      rhinoplasties and 36 had undergone open rhinoplasties; the incidence of prior
      open rhinoplasty had increased steadily over the survey years, from 21 percent in
      1996 to more than 50 percent in 1998, 1999, and 2000 (p < 0.05). The data
      generated indicate the following. First, the open rhinoplasty patients had
      undergone more operations (3.1 versus 1.2) and had more presenting complaints
      (5.8 versus 2.6) than the closed rhinoplasty patients. Second, although the most
      common presenting complaint among prior closed rhinoplasty patients was an
      overresected dorsum (50 percent) or tip (33 percent) or internal valvular
      obstruction (42 percent), prior open rhinoplasty patients complained more
      frequently than the closed rhinoplasty patients of these problems and also
      external valvular obstruction (50 percent, p < 0.0001), short nose (39 percent, p
      < 0.001), wide columella (36 percent, p < 0.001), narrow nose (31 percent, p <
      0.001), columellar scar (25 percent, p < 0.001), and symptomatic columellar
      struts (19 percent, p < 0.001). Only excessive nasal length was more prevalent
      among closed rhinoplasty patients (20 percent, p < 0.01). Third, ranking of
      deformities differed significantly (p < 0.0001) between the two groups, so that
      complaints related to the nostrils, nasal tip, nasal length, or columella were
      more common among the open rhinoplasty patients than among those previously
      treated endonasally. Fourth, the relative frequencies of surgical complaints also
      differed: whereas patients previously treated endonasally were 6.7 times more
      likely to complain of long noses, patients previously treated by open rhinoplasty
      complained more frequently of the following: excessive columellar width (open
      approach, 36 percent of patients; closed approach, none), hard columellar struts
      (open approach, 19 percent of patients; closed approach, none), external valvular
      obstruction (4.5 times as frequent with the open approach as it was with the
      closed approach), alar/nostril distortion (four times as frequent), and narrow
      nose (3.9 times). Although the most common complaints among all postrhinoplasty
      patients remain the overresected dorsum, tip, or (internal valvular) airway
      obstruction, the author's data suggest that patients previously treated by the
      open approach are more likely to have postsurgical deformities and complaints
      referable to those anatomic structures most easily reached by transcolumellar
      exposure and to techniques that can be performed more readily or aggressively
      through that access route.

PMID- 11994621
TI  - Women's psychosocial outcomes of breast augmentation with silicone gel-filled
      implants: a 2-year prospective study.
AB  - This study examined the experiences of 360 women receiving bilateral breast
      augmentation with Dow Corning's Silastic MSI (textured) or Silastic II (smooth)
      gel-filled mammary implants. Before surgery, the women completed a quantitative
      assessment of their surgical expectations and concerns. At 6, 12, and 24 months
      postoperatively, they rated their satisfaction with surgery and its specific
      psychosocial outcomes, their concerns, and benefits-to-risks appraisals of the
      augmentation. The women reported very high levels of satisfaction with the
      procedure and its psychosocial outcomes, which did not change over time.
      Throughout the 2-year period, over 90 percent of the women were satisfied with
      surgery and their resultant body-image changes. Their concerns about risks,
      reported by 19 percent before surgery, declined after surgery and remained
      subsequently stable. Most participants (75 to 85 percent) reported that the
      benefits of surgery exceeded its risks. Postoperative events such as significant
      capsular contracture that compromised aesthetic results diminished aspects of
      satisfaction, whereas less obvious events did not. Systematic analysis of
      attrition (i.e., missing assessments) did not indicate any biases because of
      complications or psychosocial outcomes. Evaluation of a possible impact of the
      publicity surrounding the Food and Drug Administration's voluntary moratorium on
      the use of silicone gel-filled breast implants, which occurred during the study,
      revealed a limited effect, if any, on women's psychosocial outcomes. Findings are
      discussed in relation to the study's methodological strengths and limitations and
      with respect to the broader context of patient care.

PMID- 11994623
TI  - Mycobacterium fortuitum infection in prosthetic breast implants.

PMID- 11994624
TI  - Treatment of double bags during rhytidectomy.

PMID- 11994626
TI  - Simplified technique for creating a youthful umbilicus in abdominoplasty.
AB  - Reimplantation of the umbilicus remains a critical aesthetic component in
      abdominoplasty and transverse rectus abdominis musculocutaneous breast
      reconstruction. Although the ideal shape of the umbilicus has been debated,
      recent studies have shown the young, thin female with an attractive abdomen tends
      to have a small, vertically oriented umbilicus. The aesthetic considerations for
      reimplantation include position, depth, shape, and location of scar. The authors
      present a technique that is expedient and reliable and that addresses each of
      these variables. The umbilicus is sutured to the rectus fascia and reimplanted
      through a vertical incision in the abdominal flap. Subdermal sutures are placed
      from the umbilicus to the linea alba superiorly and inferiorly. These sutures
      create a vertically oriented shape and place the umbilicus in the midline.
      Shortening the umbilical stalk establishes depth and hides the closure of the
      umbilicus and abdominal flap within the stalk. The stalk length is easily varied,
      depending on the thickness of the panniculus. Defatting is performed through the
      vertical incision to allow easy visualization of the umbilicus. This technique
      creates depth, ensures optimal position, pulls the scar deep in the umbilicus,
      and produces a vertically oriented, youthful umbilicus. More importantly, a
      questionnaire given to patients who have undergone abdominoplasty with this
      procedure (n = 21) confirms that patients have a high level of satisfaction with
      the resulting shape, position, and overall appearance.

PMID- 11994627
TI  - Long-term results of surgical correction of postliposuction contour
      irregularities.

PMID- 11994628
TI  - Sandwiched between.

PMID- 11994629
TI  - Martyrdom of a sort.

PMID- 11994631
TI  - Curiously shaped tongue in cleft lip and palate patient.

PMID- 11994632
TI  - Preliminary experience with botulinum toxin type B in hyperkinetic facial lines.

PMID- 11994633
TI  - Inferiorly based dermal glandular flap.

PMID- 11994634
TI  - Flexor tendon retrieval: another trick.

PMID- 11994635
TI  - Fibrous ring pulls plug on saline-filled implants.

PMID- 11994636
TI  - Radiation-induced skin ulcer, cerebral meningioma, and skin cancer following
      radiation and radium treatment for actinomycosis.

PMID- 11994637
TI  - Primary repair of cleft lip and nasal deformity.

PMID- 11994638
TI  - Solidarism.

PMID- 11994639
TI  - The "pillow box" for foot elevation.

PMID- 11994640
TI  - In search of the perfect Kirschner wire cover.

PMID- 11994641
TI  - Reflections on a day of infamy.

PMID- 11994642
TI  - Tongue revascularization.

PMID- 11994643
TI  - Necrotizing fasciitis and purpura fulminans.

PMID- 11994644
TI  - Radiologic evaluation of mandibular and dentoalveolar fractures.

PMID- 11994645
TI  - Valve design as a cause of saline-filled implant deflation.

PMID- 11994646
TI  - Do we really need extensive exposure of nerve trunks in leprosy?

PMID- 11994647
TI  - Determination of survival of human skin allografts.

PMID- 11994648
TI  - Costal cartilage for treatment of temporomandibular joint ankylosis.

PMID- 11994649
TI  - The pain-control infusion pump for postoperative pain control in plastic surgery.

PMID- 11994650
TI  - Total nipple necrosis.

PMID- 11994651
TI  - Physician suicide.

PMID- 11994664
TI  - [The 44th International Meeting on Clinical Endocrinology. Paris, France, May 17
      18, 2001. Obesity: the twists and turns of endocrinology].

PMID- 11994665
TI  - Molecular mechanisms of adipocyte differentiation.

PMID- 11994666
TI  - Autocrine/paracrine effectors of adipogenesis.

PMID- 11994667
TI  - Recent data on the regulation of lipolysis by catecholamines and natriuretic
      peptides.

PMID- 11994668
TI  - Angiogenesis in adipose tissue.

PMID- 11994669
TI  - [Determinants and control of energy expenditure].
AB  - Obesity is a risk factor for many diseases including cardio-vascular disease,
      type 2 diabetes, and certain forms of cancer, among others. Obesity results from
      a chronic imbalance between calorie intake and energy expenditure. Genetic
      factors obviously play an important role in weight gain, but only in certain
      environments. The principal cause of the obesity epidemic is not clear: is
      obesity due to excessive food intake, a dynamic reduction in energy expenditure,
      or an association of these two factors? However, most obese subjects gain weight
      because of an inaptitude to adjust energy expenditure in response to excessive
      food intake. In this article, we review briefly the respective role of genes and
      environment in the development of obesity, then describe metabolic risk factors
      involved. Longitudinal studies conducted in Pima Indians have demonstrated that a
      relative decrease in basal metabolism, weak lipid oxidation in the fasting state,
      reduced spontaneous physical activity, and lower sympathetic nervous system
      activity are risk factors for obesity. Unlike our growing knowledge of food
      intake regulation, little is known about the control of energy expenditure. New
      discoveries should provide information on obesity susceptibility genes and
      increase the chances of developing new anti-obesity treatments.

PMID- 11994670
TI  - The uncoupling proteins.

PMID- 11994671
TI  - Molecular mechanism of insulin resistance.

PMID- 11994672
TI  - Regulation of gene expression in human skeletal muscle and adipose tissue.

PMID- 11994673
TI  - Neuronal pathways regulating food intake and body adiposity.

PMID- 11994674
TI  - Melanocortin pathway: animal models of obesity and disease.

PMID- 11994675
TI  - Aspects of the neuroendocrine regulation of body weight homeostasis.

PMID- 11994676
TI  - Obesity and the reproductive axis.

PMID- 11994677
TI  - [Thyroid hormones and obesity].
AB  - Although the stimulating effect of thyroid hormones on energy metabolism has been
      recognized for more than a century, the relation between thyroid function and
      weight control and obesity remains unclear. We review here the effects of thyroid
      hormones, hyperthyroidism, and hypothyroidism on body composition and the
      parameters of energy metabolism.

PMID- 11994678
TI  - Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to
      obesity.
AB  - Obese patients show marked impairment in spontaneous secretion as well as in the
      somatotroph responsiveness to all provocative stimuli. GH insufficiency in obese
      patients has been reported reversible after long-term diet and marked weight loss
      but somatotroph secretion is not restored by fasting. Among potential
      neuroendocrine causes, GHRH hypoactivity has been shown but it is likely that
      alterations in the influence of ghrelin, the gastric-derived natural ligand of
      the GHS-R, and or of the NPY/leptin interplay could have a role. Among metabolic
      alterations, the chronic elevation of FFA levels and hyperinsulinism probably
      have a key role in causing GH insufficiency in obesity. Despite marked GH
      insufficiency, total IGF-I levels are basically preserved while free IGF-I levels
      are even increased thus questioning real hypoactivity of GH/IGF-I axis in
      obesity. Peripheral GH hypersensitivity due to increased GH receptor status,
      hyperinsulinism and reduced IGFBP-I levels likely explain almost normal total IGF
      I and increased free IGF-I levels which, in turn, probably exert an increased
      negative feedback action on somatotroph cells.

PMID- 11994679
TI  - [Central control of bone formation].

PMID- 11994680
TI  - [Prevalence of obesity in adults in France: the situation in 2000 established
      from the OBEPI Study].

PMID- 11994681
TI  - [Therapeutic options and expectations in obesity].
AB  - Obesity is now the more prevalent nutritional disease in the world. Mainly
      related to the evolution of life style, in particular sedentary, food
      availability and palatability and eating disorders, this disease is also
      dependent on psychological and environmental factors together with biological
      (genetic or not) determinants. Obesity includes a great variety of clinical,
      pathophysiological situations. This nutritional disease results from a long term,
      chronic, autoaggravating process. Complications related to the excess of adipose
      mass accumulation are metabolic, mechanic and cellular. The clinician task is to
      analyse in a given subject the relative influence of the pathophysiological
      factors, the predominant and more severe complications to adapt a tailored
      medical strategy.

PMID- 11994682
TI  - Results of obesity treatment.
AB  - Obesity is a chronic disease so that results of obesity treatment should only be
      evaluated on a long-term basis. The present paper aims at analyzing the long-term
      (1 year or more) results of three anti-obesity approaches, i.e. lifestyle
      modifications, pharmacological treatments and surgical procedures. Dietary
      interventions include diets with moderate calorie restriction and very-low energy
      diets (VLED). Even if an initial greater weight loss is observed with VLED, no
      study has conclusively shown that the long-term approaches including VLED are
      better than non-VLED programmes. Physical activity is not the most efficient
      method of initial weight loss, but it appears to be more crucial for maintaining
      weight loss once it has occurred. In general, long-term results of lifestyle
      modifications are disappointing because of poor compliance. Several 1-2 year
      large-scale randomized placebo-controlled clinical trials with orlistat, an
      intestinal lipase inhibitor, and sibutramine, a central appetite regulator, have
      demonstrated that both drugs significantly, although modestly on average,
      increase weight reduction, almost double the number of responders (weight loss
      >=5 or 10% of initial body weight) and improve weight maintenance up to 2 years.
      Surgical procedures provide a much greater weight reduction than medical
      interventions in patients with morbid obesity, particularly after a follow-up of
      several years. Weight loss is greater with gastric bypass, inducing some
      malbsorption, than with gastroplasty, a pure gastric restriction technique.
      Associated risk factors such as markers of insulin resistance syndrome and type 2
      diabetes are remarkably reduced, but no prospective study of morbidity or
      mortality is available yet. In all cases, the management of obesity requires a
      multidisciplinary approach to improve the success rate.

PMID- 11994683
TI  - New therapeutic developments in the regulation of food intake by neuropeptides.

PMID- 11994684
TI  - [Diagnostic value of clinical signs in giant cell arteritis: analysis of 415
      temporal artery biopsy findings].
AB  - AIM OF THE STUDY: The American College of Rheumatology (ACR) has proposed a list
      of criteria for diagnosis of giant cell arteritis in order to guide clinical
      research by differentiating it from other vasculitis. The aim of this
      retrospective investigation, based on the findings of 415 temporal artery
      biopsies was to assess the diagnostic value of these criteria in the daily
      clinical setting. METHODS: The demographic, clinical and biological
      characteristics of patients with positive (confirmed cases of giant cell
      arteritis) or negative (controls) histopathological temporal artery biopsy
      findings were analyzed using downward step-by-step logistic regression analysis.
      This analysis enabled investigators to list signs with inherent diagnostic value.
      Based their odds-ratio, these factors were used to determine a clinical score for
      giant cell arteritis. RESULTS: A score of over 7 - out of a maximum score of 32 -
      enables the diagnosis for giant cell arteritis with the best possible compromise
      between a sensitivity of 75.7% and a specificity of 72.2%. ACR criteria had a
      sensitivity of 97.5% and a specificity of 78.9% when used in our patient group.
      CONCLUSION: Our study results are original in that the control group was composed
      of patients in whom the diagnosis of giant cell arteritis had been suggested but
      refuted by the absence of histopathological findings on the temporal artery
      biopsy. This pragmatic attitude in selecting the control group may explain the
      difference observed with the ACR criteria in terms of sensitivity and
      specificity. Further research is needed to develop a diagnostic method for giant
      cell arteritis without resorting to temporal artery biopsy.

PMID- 11994685
TI  - [Avoidable hospital drug prescription in the elderly. A review of the
      literature].
AB  - Elderly persons are particularly exposed to drug reactions, especially drug
      interactions subsequent to multiple prescriptions. It is also recognized that the
      drug risk is the leading hospital risk involving 1 to 10% of all hospitalized
      patients. An analysis of the avoidable nature of drug reactions leads to
      consideration of a sequence of 4 events leading to drug exposure: prescription,
      delivery, administration and compliance. Each event in this sequence corresponds
      to a distinct person: physician, pharmacist, nurse, patient. This suggests that
      the prevention of drug reactions in hospitalized elderly persons requires
      implementation of an "alert-causal attributability-avoidability-prevention"
      system by the healthcare teams where physicians, pharmacists, and nurses work in
      close coordination with the patient.

PMID- 11994686
TI  - [Leflunomide in the treatment of rheumatoid arthritis].
AB  - Leflunomide is a new second-line drug for rheumatoid arthritis. This compound
      with long half-life inhibits proliferation of activated T lymphocytes. Phase III
      studies have demonstrated a clinical efficacy superior to placebo and identical
      to comparators (salazopyrine, methotrexate) with a faster onset of response.
      Improvement of inflammatory paramaters and functional capacity (HAQ) were
      observed as well as slowing of structural damage evaluated by X-rays. Global
      tolerance is fair, but possibility of hepatic involvement, although unfrequent,
      needs a regular survey.

PMID- 11994687
TI  - [New nonsteroidal antiinflammatory drugs in rheumatoid arthritis].
AB  - Cyclooxygenase functions Fundamental aspects of coxibs Efficacy of coxibs in
      rheumatoid arthritis Tolerance to coxibs Conclusion

PMID- 11994688
TI  - [TNFalpha inhibitors for the treatment of rheumatoid arthritis].
AB  - Reasons for using TNFalpha inhibitors in rheumatoid arthritis Available agents
      modulating TNFalpha Adverse effects to TNFalpha inhibitors Which patients should
      be treated with TNFalpha inhibitors? Monitoring treatment with TNFalpha
      inhibitors Patient follow-up Open questions Conclusions

PMID- 11994689
TI  - [Combination therapy for rheumatoid arthritis].
AB  - What can be expected from combination therapy? What is the goal of combination
      therapy? What criteria allow drug selection? Is combination therapy regularly
      used for controlling rheumatoid arthritis? What combination therapies have been
      assessed with clinical trials? What is the contribution of prolonged combination
      therapy? Conclusion

PMID- 11994690
TI  - [Glucocorticoid therapy for rheumatoid arthritis].

PMID- 11994691
TI  - [Sporadic Creutzfeldt-Jakob disease and isolated dementia. Contribution of brain
      MRI].
AB  - Creutzfeldt-Jakob disease (CJD) is the most frequent transmissible spongiform
      encephalopathy. Its definite diagnosis is ascertained by cerebral
      neuropathological exam. However, diagnosis of a probable or possible case of CJD
      can be evoked on the basis of Masters'classification which is based on the
      association of different clinical and electroencephalographical criteria. We
      report the case of a 58-year-old woman who died in a geriatric unit of autopsy
      proven sporadic CJD. The clinical course over 15 months was rapidly progressive
      dementia without characteristic clinical and EEG signs. The case presentation did
      not meet the criteria of probable or possible CJD, according to
      Masters'classification. However, 4 months after the onset of the disease, t-Flair
      MRI revealed an increased signal intensity in the right frontal and occipital
      cortex which could suggest the diagnosis of CJD. This case therefore stresses the
      contribution of MRI, especially diffusion-weighted imaging, for early diagnosis
      of CJD. It shows also the short comings of Masters'classification which does not
      always enable diagnosis of CJD even though control measures would have to be
      rapidly undertaken, specially the decontamination of medico-surgical equipment.
      Finally, this case illustrates the great importance of post mortem exam in such
      context. In light of this clinical observation, we discuss this rare diagnosis
      which should be considered in geriatrics when confronted with a rapidly
      progressive dementia

PMID- 11994692
TI  - [Wernicke's encephalopathy in a patient with AIDS].

PMID- 11994695
TI  - Primary cellular immunodeficiencies.
AB  - Genetic defects in T-cell function lead to susceptibility to infections or to
      other clinical problems that are more grave than those seen in disorders
      resulting in antibody deficiency alone. Those affected usually present during
      infancy with either common or opportunistic infections and rarely survive beyond
      infancy or childhood. The spectrum of T-cell defects ranges from the syndrome of
      severe combined immunodeficiency, in which T-cell function is absent, to combined
      immunodeficiency disorders in which there is some, but not adequate, T-cell
      function for a normal life span. Recent discoveries of the molecular causes of
      many of these defects have led to a new understanding of the flawed biology
      underlying the ever-growing number of defects. Most of these conditions could be
      diagnosed by means of screening for lymphopenia or for T-cell deficiency in cord
      blood at birth. Early recognition of those so afflicted is essential to the
      application of the most appropriate treatments for these conditions at a very
      early age. The latter treatments include both transplantation and gene therapy in
      addition to immunoglobulin replacement. Fully defining the molecular defects of
      such patients is also essential for genetic counseling of family members and
      prenatal diagnosis.

PMID- 11994696
TI  - T-cell activation through the antigen receptor. Part 1: signaling components,
      signaling pathways, and signal integration at the T-cell antigen receptor
      synapse.
AB  - Part 1 of this review will highlight the basic components and signaling pathways
      by which the T-cell antigen receptor (TCR) activates mature extrathymic T cells.
      TCR signaling commences with an early wave of protein tyrosine kinase activation,
      which is mediated by the Src kinases Lck and Fyn, the 70-kd zeta-associated
      protein kinase, and members of the Tec kinase family. This early wave of protein
      tyrosine phosphorylation leads to the activation of downstream signaling
      pathways, including an increase in intracellular free calcium, protein kinase C,
      nuclear factor kappaB and Ras-mitogen-activated protein kinase activation. These
      pathways activate transcription factors, such as activator protein 1, nuclear
      factor of activated T cells, and Rel proteins, which ultimately lead to the
      expression of genes that control cellular proliferation, differentiation, anergy,
      or apoptosis. This review also describes how costimulatory receptors assist in
      signal transduction and assembly of macromolecular complexes at the TCR contact
      site with the antigen-presenting cell, also known as the immune synapse. These
      basic concepts of TCR signal transduction will be used in part 2 to explain how T
      cell function can be altered by therapeutic targeting of TCR signaling
      components, as well as to explain modification of TCR signaling during
      T(H)1/T(H)2 differentiation, tolerance, and immune senescence.

PMID- 11994697
TI  - Exercise-induced asthma: is there still a case for histamine?

PMID- 11994698
TI  - Genetic markers for occupational asthma.

PMID- 11994699
TI  - Effect of 2-year placebo-controlled immunotherapy on airway symptoms and
      medication in patients with birch pollen allergy.
AB  - BACKGROUND: Birch pollen is a common allergen in northern, central, and eastern
      Europe. Earlier studies of specific immunotherapy using birch pollen extract were
      not placebo-controlled or were only preseasonal. Long-term, placebo-controlled
      studies with subcutaneously administered standardized birch pollen extract are
      lacking. OBJECTIVE: The aim of this study was to evaluate the effect of
      immunotherapy with birch pollen extract on airway symptoms and use of medication
      in adult birch pollen-allergic patients in a double-blind, placebo-controlled
      trial. METHODS: Forty-nine patients with histories of birch pollen allergy from
      the upper and lower airways, positive skin prick test and conjunctival
      provocation test results, and in vitro specific IgE to birch pollen (Betula
      verrucosa ) extract were included. Immunotherapy with birch pollen extract was
      given during 2 consecutive years in a double-blind, randomized, placebo
      controlled study. Clinical symptom scores from the upper and lower airways and
      use of rescue medication were registered throughout the pollen season. RESULTS:
      Forty-six patients reached the maintenance dose and were maintained on that dose
      during the 2-year study. The median symptom scores during the 1997 and 1998
      seasons were 1.3 and 2.6, respectively, in the specific immunotherapy group and
      2.1 and 4.3, respectively, in the placebo group. The differences between the
      groups were significant (P =.05 in 1997 and P =.005 in 1998). The placebo group
      used significantly more rescue medication during both seasons than the specific
      immunotherapy group (P =.004 for 1997 and P =.004 for 1998). CONCLUSION: Specific
      immunotherapy with birch pollen extract is an effective and safe treatment for
      reducing clinical allergy symptoms and medication use in birch pollen-allergic
      patients during the pollen season.

PMID- 11994700
TI  - Pets, parental atopy, and asthma in adults.
AB  - BACKGROUND: Studies of exposure to pets and the risk of asthma have provided
      conflicting results. OBJECTIVE: We conducted a population-based incident case
      control study to assess the relationship of current and previous pet keeping with
      the risk of adult-onset asthma. We also investigated whether genetic propensity
      as a result of parental atopy modifies these relations. METHODS: From the source
      population of 441,000 inhabitants of a geographically defined area in South
      Finland, we systematically recruited, during a 2.5-year period, all new cases of
      asthma in 21- to 63-year-old adults and randomly selected control subjects. The
      clinically diagnosed case series consisted of 521 adults with newly diagnosed
      asthma and a control series of 932 control subjects. Information on current and
      past exposure to hairy pets was collected by using a self-administered
      questionnaire. RESULTS: In logistic regression analysis the risk of asthma was
      lower among subjects with pets during the past 12 months (adjusted odds ratio
      [OR], 0.74; 95% confidence interval [CI], 0.57-0.96) but higher among subjects
      with pets more than 12 months previously (adjusted OR, 1.39; 95% CI, 1.05-1.84).
      Parental atopy increased the risk of asthma (OR, 1.88; 95% CI, 1.47-2.41), but
      there was no interaction between parental atopy and pet exposure. CONCLUSIONS:
      The present results are consistent with the hypothesis that both keeping furry
      pets and parental atopy increase the risk of asthma development in adulthood.
      Parental atopy does not modify the effects of pet exposure. The negative
      association between current pets and the risk of asthma is consistent with
      selective avoidance of these pets by symptomatic individuals.

PMID- 11994701
TI  - Influence of zafirlukast and loratadine on exercise-induced bronchoconstriction.
AB  - BACKGROUND: Airway obstruction induced by physical exercise is a common feature
      in asthma, and conventional treatments do not offer optimal protection. There is
      thus a need for additional therapies for optimal control of exercise-induced
      bronchoconstriction (EIB). OBJECTIVE: The influence of treatment with the
      antihistamine loratadine and the antileukotriene zafirlukast alone and in
      combination on EIB was investigated. This combination has previously shown
      beneficial additive effects in allergen-induced bronchoconstriction. METHODS: In
      a double-blind cross-over study loratadine (10 mg twice daily) and zafirlukast
      (80 mg twice daily) were evaluated alone and in combination in 16 nonsmoking
      patients with mild asthma, previously documented EIB, and airways
      hyperresponsiveness to histamine. RESULTS: The mean +/- SE maximum decrease in
      FEV1 after a standardized exercise provocation was 21.6% +/- 3% after placebo,
      22.8% +/- 3% after loratadine, 13.9% +/- 2% after zafirlukast (P <.05 vs
      placebo), and 10.3% +/- 2% after the combination of loratadine and zafirlukast (P
      <.05 vs placebo). Expressed as the area under the FEV1 percentage change versus
      time curve, the mean protection produced by zafirlukast and the combination of
      zafirlukast and loratadine was 57% and 65%, respectively, whereas loratadine
      alone had no significant protective effect. There was also no significant
      difference between the effect of zafirlukast alone or in combination with
      loratadine. CONCLUSION: The study confirmed the beneficial effect of a
      leukotriene receptor antagonist in EIB but failed to obtain evidence that H1
      receptor antagonism alone or together with the cysteinyl-leukotriene 1 receptor
      antagonist zafirlukast offers a protective effect.

PMID- 11994702
TI  - The efficacy of montelukast in the treatment of cat allergen-induced asthma in
      children.
AB  - BACKGROUND: Montelukast is a leukotriene antagonist approved for the treatment of
      childhood asthma in children age 2 years and older. There are limited studies on
      its effects on allergic asthma in children. OBJECTIVE: We sought to evaluate
      montelukast's effects on upper and lower airway responses to intense cat allergen
      exposure. METHODS: In a double-blind, placebo-controlled, cross-over trial 18
      subjects aged 6 to 14 years with cat-induced asthma were randomly assigned to
      receive 1 week each of either montelukast or placebo, followed by a 1-hour cat
      challenge in an environmental exposure unit. Upper and lower respiratory tract
      symptoms were rated, and spirometry and acoustic rhinometry were performed.
      Challenges were stopped early if the subject became too uncomfortable or had a
      greater than 50% decrease in FEV1. RESULTS: Overall changes in FEV1 were
      significantly different with montelukast treatment and remained significant after
      adjusting for allergen level (P =.02; adjusted P =.01). Lower respiratory tract
      symptom scores were significantly reduced with montelukast versus placebo (P
      =.007) but lost significance after adjusting for allergen level (P =.16).
      Challenge length was significantly longer with montelukast versus placebo (P
      <.001) and remained significant after adjusting for allergen level (P =.019).
      Montelukast did not significantly affect upper respiratory responses, as measured
      by means of symptom scores (P =.43) and changes in acoustic rhinometry (P =.078).
      CONCLUSIONS: Montelukast was significantly more effective than placebo in
      attenuating lower respiratory responses and extending challenge length when cat
      sensitive children with mild persistent asthma were exposed to high levels of cat
      allergen.

PMID- 11994703
TI  - Mode of delivery and risk of developing allergic disease.
AB  - The aim of this study was to quantify the relationship between mode of delivery
      and subsequent incidence of allergic disease. The analysis is based on data
      derived from a birth cohort of 24,690 children who contributed data to the West
      Midlands General Practice Research Database. We found no convincing evidence to
      suggest that babies born by caesarean, forceps, or breech delivery had an
      increased risk of developing allergic disease.

PMID- 11994704
TI  - IFN-gamma secretion by CD8T cells inhibits allergen-induced airway eosinophilia
      but not late airway responses.
AB  - BACKGROUND: CD8+T cells can suppress allergen-induced late airway responses
      (LARs) and airway inflammation. OBJECTIVE: To test the hypothesis that the
      suppression of LARs and airway eosinophilia by CD8+T cells is IFN-gamma mediated,
      we tested the effects of adoptively transferred CD8+T cells, in which IFN-gamma
      synthesis was inhibited by an antisense (AS) oligodeoxynucleotide (ODN), on the
      airway responses of a rat model of allergic asthma. METHODS: CD8+T cells were
      harvested from the cervical lymph nodes of ovalbumin (OVA)-sensitized Brown
      Norway rats for administration to other actively sensitized syngeneic rats. CD8+T
      cells (2 x 10(6)) were incubated for 6 hours with 2 micromol/L AS ODN or sense
      ODN and were injected intraperitoneally into recipients; inhibition of IFN-gamma
      expression in vitro by AS ODN was shown by means of flow cytometry. Two days
      later, rats were challenged with aerosolized OVA. RESULTS: OVA-induced LAR and
      bronchoalveolar lavage (BAL) fluid eosinophilia were suppressed by sense ODN
      treated CD8+T cells. IFN-gamma expression in BAL cells was elevated in these
      animals. IFN-gamma expression in BAL cells was at control levels in recipients of
      AS ODN-treated CD8+ cells, confirming the success of the AS treatment in vivo.
      BAL eosinophilia was also largely restored in the AS ODN treatment group. In
      contrast, the CD8+T cell-induced suppression of the LAR was not significantly
      affected by AS ODN pretreatment. CONCLUSIONS: These results indicate that CD8+T
      cells inhibit airway eosinophilia through secretion of IFN-gamma but may suppress
      the LAR by means of other mechanisms.

PMID- 11994705
TI  - Adoptive transfer of T cells induces airway hyperresponsiveness independently of
      airway eosinophilia but in a signal transducer and activator of transcription 6
      dependent manner.
AB  - BACKGROUND: Activated T cells, through the release of specific cytokines (ie, IL
      4, IL-5, and IL-13), regulate effector cell recruitment and function. In this way
      T cells orchestrate the inflammatory response, which leads to airway
      hyperresponsiveness (AHR), a cardinal feature of allergic asthma. OBJECTIVE: In
      the present study the direct role of T cells and, in particular, the importance
      of signal transducer and activator of transcription 6 (STAT6) in T cells was
      investigated in the development of AHR. METHODS: In a murine model of allergen
      driven AHR, the effects of adoptive transfer of STAT6-containing (STAT6+/+) and
      STAT6-deficient (STAT6-/-) T cells from sensitized mice into allergen-challenged
      mice were tested. RESULTS: Although greater in STAT6+/+ mice, both allergen
      challenged STAT6+/+ and STAT6-/- mice had AHR after transfer of T cells from
      sensitized STAT6+/+ mice. In contrast, AHR did not develop in allergen-challenged
      STAT6-/- mice after transfer of T cells from sensitized STAT6-/- mice.
      Reconstitution of AHR after T-cell transfer was not associated with airway
      eosinophilia. CONCLUSIONS: The data indicate that the STAT6 status of the donor
      mice is critical to the development of AHR. Although not critical for the
      development of AHR, the STAT6 status of the recipient mice might play a
      contributory-regulatory role in the AHR response. The results identify a STAT6
      dependent T-cell pathway capable of modulating airway responsiveness, even in the
      absence of a significant airway eosinophilia.

PMID- 11994706
TI  - Activation markers of human basophils: CD69 expression is strongly and
      preferentially induced by IL-3.
AB  - BACKGROUND: The biological functions of basophils are precisely regulated by
      various cytokines in vitro, but little is known about surface markers that are
      upregulated during the cytokine-mediated activation process. OBJECTIVE: It has
      been well established that CD69, CD44, and CD54 represent "activation markers"
      for cytokine-mediated eosinophil activation. The objective of this study was to
      elucidate the expression and regulation of these molecules in human basophils in
      vitro as well as in vivo. METHODS: Basophils were purified from venous blood by
      means of density gradient centrifugation followed by negative selection. Surface
      expression was analyzed by means of flow cytometry. We also studied the
      expression of CD69, CD44, and CD54 on basophils in bronchoalveolar lavage fluid
      and blood specimens from patients with asthma. RESULTS: CD44 and CD54 were
      constitutively expressed on basophils and moderately upregulated by IL-3. On the
      other hand, CD69 expression was only weakly observed in freshly isolated
      basophils, but IL-3 induced extremely high levels of expression. Surface CD69
      appeared rather slowly in comparison with CD63 and CD11b, and the induction of
      expression was completed within 24 hours. Basophil CD69 had no functional
      relevance, but it did have biological relevance. Whole blood basophils from
      asthmatic individuals expressed significantly higher levels of CD69 than did
      those from normal individuals. Furthermore, bronchoalveolar lavage fluid
      basophils showed higher levels of CD69 expression than did blood basophils from
      the same donors. CONCLUSION: CD69 expression on basophils was preferentially and
      strongly upregulated by IL-3. CD69 on basophils might be useful as an in vitro as
      well as in vivo marker of activation of these cells by IL-3.

PMID- 11994707
TI  - Cyclooxygenase 1 and cyclooxygenase 2 expression is abnormally regulated in human
      nasal polyps.
AB  - BACKGROUND: There is evidence that impairment of prostanoid metabolism might be
      involved in the pathogenesis of nasal polyps (NPs). Prostanoids are synthesized
      by 2 cyclooxygenase (Cox) enzymes, one constitutive (Cox-1) and another inducible
      (Cox-2). OBJECTIVE: The aim of these studies was to investigate Cox-1 and Cox-2
      regulation in NPs of aspirin-tolerant human patients compared with that seen in
      nasal mucosa (NM). METHODS: Cultured explants from human NPs and healthy mucosa
      from patients undergoing polypectomy and corrective nasal surgery, respectively,
      were examined for Cox-1 and Cox-2 expression by means of semiquantitative
      competitive PCR and Western blotting. RESULTS: Cox-1 mRNA was spontaneously
      upregulated in cultured NM but not in NPs. A spontaneous but delayed upregulation
      of Cox-2 mRNA was found in NPs (24 hours) compared with that seen in NM (6
      hours). After cytokine stimulation (IFN-gamma, IL-1beta, and TNF-alpha), the
      induction of Cox-2 mRNA and protein was also faster in NM (1 hour) than in NPs (4
      hours). CONCLUSION: These data showing an abnormal regulation of Cox-1 and Cox-2
      in NPs from aspirin-tolerant patients reinforce the concept that prostanoid
      metabolism might be important in the pathogenesis of inflammatory nasal diseases
      and suggest a potential role for this alteration in the formation of NPs.

PMID- 11994708
TI  - Lipid mediators from pollen act as chemoattractants and activators of
      polymorphonuclear granulocytes.
AB  - BACKGROUND: Under natural exposure conditions, pollen grains function as allergen
      carriers that release allergens from internal binding sites on contact with the
      aqueous phase of mucosa membranes. In addition, we recently demonstrated that
      pollen are a rich source of eicosanoid-like mediators, which are rapidly released
      on contact with the aqueous phase. OBJECTIVE: The current study was designed to
      characterize the biochemical nature of pollen-derived lipid mediators in more
      detail and to delineate their biologic activity on polymorphonuclear granulocytes
      (PMNs). METHODS: Aqueous and lipid extracts from Phleum pratense L and Betula
      alba L pollen were analyzed by means of HPLC. PMNs were exposed to aqueous
      extracts or lipid fractions from pollen or to HPLC-purified lipid mediators
      identified in pollen extracts. Effects on PMNs were tested with transwell
      migration, calcium mobilization, and surface expression of CD11b. RESULTS:
      Aqueous pollen extracts (APEs) contained predominantly monohydroxylated products
      derived of linoleic acid and linolenic acid. In chemotaxis assays PMNs displayed
      significant migration to APEs. Lipid extracts from pollen and the HPLC fraction
      containing 13-hydroxy-octadecadienoic acid/hydroxy-linoleic acid and 13-hydroxy
      octadecatrienoic acid/hydroxy-linolenic acid induced migratory responses,
      although to a lesser degree than the APEs. In addition, APE, as well as lipid,
      extracts induced PMN activation, as documented by means of calcium mobilization
      and upregulation of CD11b. CONCLUSION: Pollen grains release mediators that
      recruit and activate PMNs in vitro. Similar mechanisms may be effective in vivo,
      suggesting that pollen-derived lipid mediators may act as adjuvants in the
      elicitation phase of allergic reactions.

PMID- 11994709
TI  - Expression and function of histamine receptors in human monocyte-derived
      dendritic cells.
AB  - BACKGROUND: Histamine is a well-known mediator eliciting different responses in
      immune and nonimmune cells, but its role in modulating dendritic cell (DC)
      functions has been marginally investigated. OBJECTIVE: The purpose of this
      investigation was to analyze whether human monocyte-derived DCs express
      functional histamine receptors according to their maturation stage. METHODS: DCs
      were derived from monocytes and used as immature or LPS-differentiated cells. DCs
      were tested for histamine receptor expression, chemotaxis, cytokine release, and
      the capacity to induce T-cell differentiation in response to specific histamine
      receptor agonists. RESULTS: Immature and mature DCs expressed the mRNA for H1,
      H2, and H3 histamine receptors. Histamine induced intracellular Ca2+ transients,
      actin polymerization, and chemotaxis in immature DCs. Maturation of DCs resulted
      in the loss of these responses. In maturing DCs, however, histamine dose
      dependently enhanced intracellular cAMP levels and stimulated IL-10 secretion
      while inhibiting production of IL-12. As a consequence, histamine might
      contribute to the impairment of generation of allogeneic type 1 responses via
      maturing DCs. Specific histamine receptor agonists or antagonists revealed that
      Ca2+ transients, actin polymerization, and chemotaxis of immature DCs were due to
      stimulation of H1 and H3 subtypes. Modulation of IL-12 and IL-10 secretion by
      histamine involved the H2 and H3 receptors exclusively. CONCLUSIONS: Our study
      suggests that histamine has important biological effects on DC activities,
      opening the possibility that histamine released during inflammatory or immune
      responses could regulate DC functions and ultimately favor type 2 lymphocyte
      dominated immunity.

PMID- 11994710
TI  - Chemical constituents of diesel exhaust particles induce IL-4 production and
      histamine release by human basophils.
AB  - BACKGROUND: An epidemiologic relationship between airway allergic diseases and
      exposure to atmospheric pollutants has been demonstrated and suggested to be one
      factor in the increasing prevalence of asthma. Diesel exhaust particles (DEPs)
      have been shown to participate in the development of allergic airway
      inflammation, in which the targets include macrophages, B and T cells, epithelial
      cells, and mast cells. In addition to the adjuvant effect of DEPs on total and
      allergen-specific IgE production, DEPs also act to induce chemokines and
      cytokines and may play a key role in primary sensitization. OBJECTIVE: DEPs have
      been shown to increase local IL-4-containing Kit(+) cells soon after in vivo
      nasal challenge. The aim of this study was to examine the effects of DEPs on
      human basophils, a key source of IL-4. METHODS: Peripheral blood leukocytes from
      allergic and control subjects were cultured in the presence of organic extracts
      of DEP (DEPex) with or without allergen. The cultures were analyzed for IL-4
      containing cells by using multiparameter flow cytometry, IL-4 secretion with
      ELISA, and histamine release. RESULTS: Basophils, when exposed in vitro to DEPex,
      expressed IL-4 and released histamine significantly (P <.01) more than with
      antigen activation. DEPex did not synergize with allergen in cytokine production
      and histamine release. DEPex-induced basophil IL-4 expression peaked at 2 hours
      and persisted through 20 hours, in contrast to allergen-induced IL-4, which was
      transient. The effect of DEPex on basophil cytokine expression and histamine
      release was dose dependent and occurred with cells from both allergic and
      nonallergic subjects. DEPex induced IL-4 expression and histamine release in
      highly enriched basophil populations, suggesting it acts directly on basophils.
      Other peripheral blood leukocytes, including T cells, did not contribute to this
      cytokine expression. Preincubation with N-acetylcysteine completely abrogated
      DEPex-driven basophil IL-4 expression. CONCLUSIONS: Basophils are a direct target
      for DEPex, inducing IL-4 expression and histamine release in an IgE-allergen
      independent fashion. N-acetylcysteine inhibition of DEPex-driven IL-4 expression
      provides evidence that generation of reactive oxygen species is required for the
      effects observed. The capability of DEPex to activate basophils in both allergic
      and nonallergic subjects suggests a potential role of this pollutant in the
      increasing prevalence of allergic diseases.

PMID- 11994711
TI  - Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with
      elevation of proinflammatory cytokine IFN-gamma during the isolation of the
      Antarctic winter.
AB  - Cellular immune function has been shown to be decreased and latent virus shedding
      to be increased in human beings isolated during the Antarctic winter, a model
      used for assessing some effects of space flight. However, the balance of
      proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines
      has not previously been evaluated. We therefore sought to determine whether
      isolation during the Antarctic winter would alter the proinflammatory and anti
      inflammatory cytokine balance. Cytokine levels were measured with ELISA in
      monthly plasma samples from January through September 1999 in 21 study subjects
      in the Antarctic and 7 control subjects on Macquarie Island. There was a
      significant time-dependent increase in plasma IFN-gamma (P =.039) as well as
      decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared
      with the control subjects. The study subjects also had significantly increased
      plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P <
      or =.036) at individual time points of isolation. Isolation of human beings in
      the Antarctic appears to shift the plasma cytokine balance toward a
      proinflammatory profile. These observations are consistent with T-cell activation
      that might be due to activation of latent viruses, and they could hold importance
      for determining the risks of space flight.

PMID- 11994712
TI  - Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with
      the subsequent development of atopy, eczema, or both.
AB  - BACKGROUND: Exposure to various microbial products in early life reduces the risk
      of atopy. Such exposure induces downregulation of T(H)2 allergy-biased responses
      by means of pattern recognition molecules, such as CD14, an LPS receptor.
      OBJECTIVE: We sought to determine whether infant and maternal levels of soluble
      CD14 (sCD14) are associated with the atopic outcomes of infants. METHODS: Levels
      of sCD14 in plasma, amniotic fluid, and breast milk were measured with a specific
      ELISA in different cohorts. Expression of toll-like receptors in the fetal gut
      was examined by using RT-PCR. RESULTS: Soluble CD14 levels increased during fetal
      development and postnatally, attaining adult levels by around 4 months of age,
      with an overshoot of adult levels from 6 months of age. There was no difference
      in plasma sCD14 levels at birth of children with a high compared with those with
      a low risk of development of atopy. Amniotic fluid sCD14 levels at midgestation
      (16-17 weeks) were significantly lower when the child was subsequently atopic (P
      <.05). Soluble CD14 levels in breast milk collected 3 months postpartum were
      significantly lower in children with eczema at 6 months of age, irrespective of
      whether they were atopic (P =.003). Transcripts for toll-like receptor 4, which
      would enable transmembrane signaling for LPS/sCD14 complexes, were expressed
      within fetal gut and skin. CONCLUSION: Exposure to reduced levels of sCD14 in the
      fetal and neonatal gastrointestinal tract is associated with the development of
      atopy, eczema, or both. Thus the exogenous supply of sCD14 might influence
      immunologic reactivity both locally and systemically in early life and thereby
      influence disease outcome.

PMID- 11994713
TI  - Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma
      induced by isocyanates.
AB  - BACKGROUND: Polymorphism at the pi class glutathione-S-transferase locus (GSTP1)
      is associated with allergen-induced asthma and related phenotypes. OBJECTIVE: We
      sought to determine whether GSTP1 polymorphism influences susceptibility to
      asthma induced by toluene diisocyanate (TDI). METHODS: The role of GSTP1 was
      assessed in 131 workers exposed to TDI, 92 with TDI-induced asthma and 39
      asymptomatic subjects. The phenotype of the disease was characterized by using
      detailed clinical history, lung volumes, airway responsiveness to methacholine,
      and airway responsiveness to TDI. GST genotypes were determined by using PCR
      based assays. RESULTS: In patients exposed to TDI for 10 or more years, the
      frequency of the GSTP1 Val/Val genotype was lower in subjects who had asthma
      (odds ratio, 0.23; 95% confidence interval, 0.05-1.13; P =.074). Similarly, the
      frequency of this genotype was significantly lower in subjects with evidence of
      moderate-to-severe airway hyperresponsiveness to methacholine compared with the
      frequency in subjects with normal or mild hyperresponsiveness (P =.033).
      CONCLUSION: These data suggest that homozygosity for the GSTP1*Val allele confers
      protection against TDI-induced asthma and airway hyperresponsiveness. This view
      is supported by the finding that the protective effect increases in proportion to
      the duration of exposure to TDI.

PMID- 11994714
TI  - A novel mouse model of diisocyanate-induced asthma showing allergic-type
      inflammation in the lung after inhaled antigen challenge.
AB  - BACKGROUND: Exposure to diisocyanates, a group of highly reactive, low-molecular
      weight compounds, is a major cause of occupational asthma. In contrast to mouse
      models of atopic asthma, previous mouse models of diisocyanate-induced asthma
      have failed to show lung inflammation with characteristics of human disease.
      OBJECTIVE: Our goal was to establish a novel mouse model of diisocyanate-induced
      asthma in which lung inflammation reminiscent of that seen in human asthma is
      generated after inhaled antigen challenge. METHODS: BALB/c mice were
      epicutaneously sensitized to hexamethylene diisocyanate (HDI) and then challenged
      with an HDI-protein conjugate administered by means of an intranasal droplet.
      RESULTS: HDI sensitization resulted in development of contact hypersensitivity
      and HDI-specific antibody production. Most importantly, however, vigorous
      inflammatory responses with characteristics of human asthma were generated in the
      lung after inhaled HDI challenge. Challenge of sensitized, but not unsensitized,
      mice resulted in airway eosinophilia, mucus hypersecretion, and production of
      T(H)1-type (IFN-gamma) and T(H)2-type (IL-4, IL-5, and IL-13) cytokines by lung
      inflammatory cells. Despite the mixed T(H)1/T(H)2 response induced by HDI
      sensitization, use of cytokine-deficient mice revealed that airway eosinophilia
      was mediated by T(H)2 cytokines and not by IFN-gamma. CONCLUSION: We report a
      novel mouse model of diisocyanate-induced asthma that, in contrast to previous
      models, demonstrates antigen-induced lung inflammation with characteristics of
      human disease. This model will allow investigation of the immunopathogenesis of
      diisocyanate-induced asthma and should provide insight into this common form of
      occupational disease.

PMID- 11994715
TI  - Local allergic reaction in food-hypersensitive adults despite a lack of systemic
      food-specific IgE.
AB  - BACKGROUND: Objective tools are lacking for the diagnosis of local
      gastrointestinal inflammatory reactions in skin prick test (SPT)-negative and
      serum IgE antibody (s-IgE Ab)-negative patients with suspected food allergy.
      OBJECTIVE: The purpose of this investigation was to evaluate the presence of
      eosinophils, T cells, local IgE-bearing cells, IL-4, and IFN-gamma in small
      intestinal biopsy specimens from adult SPT-negative/s-IgE Ab-negative patients
      with food allergy during symptomatic and nonsymptomatic periods. METHODS:
      Fourteen patients with food allergy-related gastrointestinal symptoms confirmed
      by double-blinded, placebo-controlled food challenge (DBPCFC) were investigated.
      Eleven of the patients were SPT-negative and s-IgE Ab-negative. Sex- and age
      matched healthy volunteers were used as controls. Duodenal biopsies were studied
      with immunostaining through use of a panel of mouse monoclonal antibodies
      specific for eosinophils, CD3, CD4, CD8, IgE, IL-4, and IFN-gamma. RESULTS:
      Significant increases in numbers of MBP+ eosinophils, IgE-bearing cells, and T
      cells were found in the duodenal mucosa of the patients when they were
      symptomatic in comparison with when they were asymptomatic and in comparison with
      healthy controls. Numbers of IL-4+ cells were increased and numbers of IFN-gamma+
      cells were reduced in the patients when they were symptomatic in comparison with
      when they were asymptomatic and in comparison with the controls. There were no
      differences in total s-IgE levels between any of the groups. CONCLUSION: A
      significant correlation was found between the appearance of symptoms of food
      hypersensitivity and the duodenal presence of IgE-bearing cells, activated
      eosinophils, and T cells in patients with negative SPT results and negative s-IgE
      Ab to the offending food. We suggest that a localized IgE-mediated response
      caused the gastrointestinal symptoms seen in these patients.

PMID- 11994716
TI  - Drug reaction to ceftriaxone in a child with X-linked agammaglobulinemia.

PMID- 11994717
TI  - Allergy to Parietaria pollen and the ETAC study. Early Treatment of the Atopic
      Child.

PMID- 11994719
TI  - Foreword.

PMID- 11994720
TI  - The burden of asthma with specific reference to the United States.
AB  - During the second half of the 20th century, the increasing prevalence, morbidity,
      economic burden, and, in some countries, mortality from asthma have generated
      worldwide concern. The prevalence in the United States and other English-speaking
      countries is higher than that in most other countries, but worldwide variations
      cannot be explained by current knowledge of recognized risk or protective
      factors. According to hospital admission rates, asthma morbidity rates have also
      risen throughout the world during the past 40 years. These trends are likely due
      to many different factors, including an increase in the prevalence of severe
      asthma. Asthma mortality rates gradually declined in the United States during the
      1960s and 1970s but have exhibited a substantial, progressive increase during the
      past 20 years. This trend stands in contrast to those in most other western
      countries, where asthma mortality rates have generally been decreasing during the
      1990s. In both western and developing countries, the considerable economic burden
      of asthma disproportionately affects individuals with severe disease. This
      observation illustrates the potential for reducing the costs associated with
      asthma through management approaches that have been proven to reduce morbidity
      and mortality.

PMID- 11994721
TI  - Asthma: addressing consistency in results from basic science, clinical trials,
      and observational experience.
AB  - The basic science understanding of the pathophysiology of a disease often serves
      as the basis for clinical investigations. This knowledge is used to propose new
      directions in care and confirm initial concepts. The basic science of asthma
      demonstrates that the most comprehensive management of inflammation appears to be
      associated with the use of inhaled corticosteroids and proposes a mechanism for
      combination therapy with the addition of salmeterol. Randomized clinical trials
      are performed to confirm these initial observations and demonstrate both the
      safety and efficacy of therapeutic agents. These investigations are either
      placebo-controlled or direct comparisons of 2 medications. For the treatment of
      asthma, these studies have all consistently demonstrated that inhaled
      corticosteroids are the most effective primary controller therapy. Greater
      improvement in both lung function and patient-oriented symptom control is
      observed with the use of inhaled corticosteroids. For patients whose symptoms are
      not controlled with single-drug therapy, the addition of a long-acting
      bronchodilator appears to be the most effective add-on treatment with the
      greatest improvement in lung function and symptom control. Clinical trials have
      been used for the purposes of cost modeling. Therapies that produce the greatest
      effect size at the lowest incremental costs produce the greatest improvement in
      cost-effectiveness. Retrospective claims analysis, more recently, have been used
      to validate these observations from clinical trials. These studies measure both
      resource use and costs or charges. These analyses have confirmed that initial
      treatment with inhaled corticosteroids and combined treatment with inhaled
      corticosteroids and long-acting bronchodilators are the most effective stepwise
      approaches to the treatment of asthma.

PMID- 11994722
TI  - Approaching value in asthma management: the need to integrate clinical and
      economic research with the basic science.
AB  - In the management of asthma, clinical decision making is primarily directed
      toward achieving the best outcome for the patient. However, the interests of the
      provider, insurer, and employer must also be taken into account. Integral to this
      process is an understanding of the need to weigh therapeutic objectives against
      economic concerns. This process involves consideration of the potential for
      clinical benefit as opposed to adverse treatment effects, as well as direct and
      indirect costs. Data from clinical trials provide the foundation for evaluating
      these factors. Randomized clinical trials, postmarketing studies, surveillance
      programs, and observational claims analyses all contribute valuable information
      to facilitate this process. Taken together, the results of such analyses form a
      foundation for providing effective, safe, and cost-efficient care through the
      practice of evidence-based medicine.

PMID- 11994723
TI  - Establishing value in managed care: cost-effectiveness or budgetary impact?
AB  - In the managed care setting, pharmacy benefit managers face considerable
      challenges when making decisions regarding drug coverage. Although scientifically
      valid data may be available from randomized, double-blind, placebo-controlled
      trials, this type of information does not shed light on potential differences
      between medications in the same class. Furthermore, properly designed,
      comparative trials are rarely conducted. Randomized naturalistic or pragmatic
      pharmacoeconomic studies can provide valuable information but are likewise
      infrequently performed. Economic modeling is an alternative but is not widely
      accepted because of the potential for bias. Retrospective analyses of information
      from patient surveys or existing databases are emerging as more popular methods
      of supporting informed formulary decisions. In the absence of a large-scale,
      prospective, naturalistic, pharmacoeconomic study, an alternative indication of
      product superiority can be derived from a continuum of different types of studies
      (from basic science to clinical trials to retrospective pharmacoeconomic
      analysis) conducted in a variety of patient care settings. The consistency with
      which a product demonstrates superiority across all types of studies is critical
      and is a crucial determinant of whether a health care provider would be likely to
      use the information for the purpose of decision making.

PMID- 11994725
TI  - Why are helicopters so expensive? Part 2.

PMID- 11994726
TI  - Neonatal transport issues with prostaglandin E1 infusions.

PMID- 11994727
TI  - Air medical accidents attributed to maintenance.

PMID- 11994728
TI  - Intravenous fomepizole: treating ethylene glycol and methanol toxicity.

PMID- 11994729
TI  - Pediatric advanced life support guidelines updated, Part 1.

PMID- 11994730
TI  - Payor contracts: the good, the bad, and the ugly.

PMID- 11994731
TI  - CAMTS publishes fifth edition of accreditation standards.

PMID- 11994732
TI  - Air medical transport of suspected aortic emergencies.
AB  - PURPOSE: To review and characterize 4 years of experience with suggested
      nontraumatic aortic emergencies (dissections/ruptures) transported by a new,
      provincially dedicated rotor-wing air medical program METHODS: Retrospective 4
      year review of air medical program's mission records and review of related
      hospital records. Patients listed as suspected aortic emergencies (nontraumatic)
      in the air medical records were included. Mission records were reviewed for EMS
      diagnosis, blood pressures before and after transport, transport times, and
      mortality. Hospital records were reviewed for diagnosis, interventions/treatment,
      and mortality. Blood pressures below 80 mmHg systolic were considered
      hemodynamically unstable. RESULTS: A cohort of 34 patients were identified, of
      whom 31 (91%) arrived at the hospital alive. Twenty-five patients (74%) arrived
      hemodynamically stable, with a mean out-of-hospital time of 60 minutes, and nine
      patients (26%) were hemodynamically unstable (mean out-of-hospital time was 54
      minutes). No significant difference arose in times between these two groups (P =
      0.16). Overall mortality was 53% (18). Differences in transport time between
      survivors and deaths was not statistically significant (P = 0.93). The diagnoses
      on admission to hospital: 14 (41%) were RAAA, five (15%) AAA no rupture, eight
      (24%) aortic dissections, and four (12%) had no aortic pathology. Seventeen
      patients (50%) received emergent surgical intervention. The EMS diagnosis was
      correct in 76% of cases. CONCLUSION: Our program transported 34 suspected aortic
      emergencies of which 17 were immediate surgical candidates on arrival. Aortic
      emergencies are not infrequent within our program. Specific policies and
      procedures based on continuing quality review should be in place to optimize the
      transport and care of these patients.

PMID- 11994733
TI  - A turbulent novel indication for ondansetron.

PMID- 11994734
TI  - Accessibility and distribution of the Norwegian National Air Emergency Service:
      1988-1998.
AB  - OBJECTIVE: To evaluate the accessibility and distribution of the Norwegian
      National Air Emergency Service in the 10-year period from 1988 to 1998. MATERIAL
      AND METHODS: The primary material was annual standardized activity data that
      included all helicopter missions. A multivariate model of determinants for use of
      the helicopter service was computed by linear regression. Accessibility was
      measured as the percentage of the population reached in different flying times,
      and we evaluated the service using a simulation of alternative locations for the
      helicopter bases. RESULTS: The helicopter service (HEMS) has short access times,
      with a mean reaction time of 8 minutes and a mean response time of 26 minutes for
      acute missions. Nearly all patients (98%) are reached within 1 hour. A simulation
      that tested alternative locations of the helicopter bases compared with current
      locations showed no increase in accessibility. The use of the service shows large
      regional differences. Multivariate analyses showed that the distances of the
      patients from the nearest helicopter base and the nearest hospital are
      significant determinants for the use of HEMS. CONCLUSION: Establishment of a
      national service has given the Norwegian population better access to highly
      qualified prehospital emergency services. Furthermore, the HEMS has a
      compensating effect in adjusting for differences in traveling distances to a
      hospital. Safety, cost-containment, and gatekeeper functions remain challenges.

PMID- 11994735
TI  - A case review: near fatal residential hydrogen sulfide exposure.

PMID- 11994736
TI  - The snail superfamily of zinc-finger transcription factors.
AB  - The Snail superfamily of zinc-finger transcription factors is involved in
      processes that imply pronounced cell movements, both during embryonic development
      and in the acquisition of invasive and migratory properties during tumour
      progression. Different family members have also been implicated in the signalling
      cascade that confers left right identity, as well as in the formation of
      appendages, neural differentiation, cell division and cell survival.

PMID- 11994737
TI  - Dynamic localization of proteins and DNA during a bacterial cell cycle.
AB  - A cellular differentiation programme that culminates in an asymmetric cell
      division is an integral part of the cell cycle in the bacterium Caulobacter
      crescentus. Recent work has uncovered mechanisms that ensure the execution of
      many events at different times during the cell cycle and at specific places in
      the cell. Surprisingly, in this one-micron bacterial cell, the dynamic spatial
      disposition of regulatory proteins, structural proteins and specific regions of
      the chromosome are important components of both cell-cycle progression and the
      generation of daughter cells with different cell fates.

PMID- 11994738
TI  - Phosphotyrosine-binding domains in signal transduction.
AB  - Protein phosphorylation provides molecular control of complex physiological
      events within cells. In many cases, phosphorylation on specific amino acids
      directly controls the assembly of multi-protein complexes by recruiting phospho
      specific binding modules. Here, the function, structure, and cell biology of
      phosphotyrosine-binding domains is discussed.

PMID- 11994739
TI  - How cells change their phenotype.
AB  - Recent attention has focused on the remarkable ability of adult stem cells to
      produce differentiated cells from embryologically unrelated tissues. This
      phenomenon is an example of metaplasia and shows that embryological commitments
      can be reversed or erased under certain circumstances. In some cases, even fully
      differentiated cells can change their phenotype (transdifferentiation). This
      review examines recently discovered cases of metaplasia, and speculates on the
      potential molecular and cellular mechanisms that underlie the switches, and their
      significance to developmental biology and medicine.

PMID- 11994740
TI  - Messenger-RNA-binding proteins and the messages they carry.
AB  - From sites of transcription in the nucleus to the outreaches of the cytoplasm,
      messenger RNAs are associated with RNA-binding proteins. These proteins influence
      pre-mRNA processing as well as the transport, localization, translation and
      stability of mRNAs. Recent discoveries have shown that one group of these
      proteins marks exon exon junctions and has a role in mRNA export. These proteins
      communicate crucial information to the translation machinery for the surveillance
      of nonsense mutations and for mRNA localization and translation.

PMID- 11994741
TI  - Matrix metalloproteinases: a tail of a frog that became a prince.
AB  - It is 40 years since the first member of what came to be known as the matrix
      metalloproteinase (MMP) family was described. Structural, molecular and
      biochemical approaches have subsequently contributed to piecing together the
      puzzle of how MMPs work, and how they contribute to various disease processes.

PMID- 11994742
TI  - Does nitric oxide modulate mitochondrial energy generation and apoptosis?
AB  - The physiological role of nitric oxide (NO) in the maintenance of vascular tone,
      in synaptic transmission and in cellular defence is now firmly established.
      Recent evidence indicates that NO can also affect mitochondrial function. Here,
      we review findings indicating that NO   through its interaction with components
      of the electron-transport chain   might function not only as a physiological
      regulator of cell respiration, but also to augment the generation of reactive
      oxygen species by mitochondria, and thereby trigger mechanisms of cell survival
      or death.

PMID- 11994743
TI  - v-Src's hold over actin and cell adhesions.
AB  - The oncoprotein v-Src and its cellular homologue (c-Src) are tyrosine kinases
      that modulate the actin cytoskeleton and cell adhesions. Through the concerted
      action of their protein-interaction and kinase domains, they are targeted to cell
      matrix integrin adhesions or cadherin-dependent junctions between epithelial
      cells, where they phosphorylate substrates that induce adhesion turnover and
      actin re-modelling. Recent experiments have defined some of the key targets and
      effector pathways that mediate the pleiotropic oncogenic effects of v-Src.

PMID- 11994744
TI  - Retro-translocation of proteins from the endoplasmic reticulum into the cytosol.
AB  - Proteins that are misfolded in the endoplasmic reticulum are transported back
      into the cytosol for destruction by the proteasome. This retro-translocation
      pathway has been co-opted by certain viruses, and by plant and bacterial toxins.
      The mechanism of retro-translocation is still mysterious, but several aspects of
      this process are now being unravelled.

PMID- 11994745
TI  - Megalin and cubilin: multifunctional endocytic receptors.
AB  - The ability to take up substances from the surrounding environment not only
      provides cells with vital nutrients, but also enables the selective transport of
      substances from one compartment to another. Megalin and cubilin are two
      structurally different endocytic receptors that interact to serve such functions.
      Evidence has accumulated in recent years to indicate that these receptors have
      important functions in both normal physiology and pathology.

PMID- 11994746
TI  - Regulated transport of the glucose transporter GLUT4.
AB  - In muscle and fat cells, insulin stimulates the delivery of the glucose
      transporter GLUT4 from an intracellular location to the cell surface, where it
      facilitates the reduction of plasma glucose levels. Understanding the molecular
      mechanisms that mediate this translocation event involves integrating our
      knowledge of two fundamental processes--the signal transduction pathways that are
      triggered when insulin binds to its receptor and the membrane transport events
      that need to be modified to divert GLUT4 from intracellular storage to an active
      plasma membrane shuttle service.

PMID- 11994747
TI  - Closing in on the biological functions of Fps/Fes and Fer.
AB  - Fps/Fes and Fer are the only known members of a distinct subfamily of the non
      receptor protein-tyrosine kinase family. Recent studies indicate that these
      kinases have roles in regulating cytoskeletal rearrangements and inside out
      signalling that accompany receptor ligand, cell matrix and cell cell
      interactions. Genetic analysis using transgenic mouse models also implicates
      these kinases in the regulation of inflammation and innate immunity.

PMID- 11994748
TI  - The evolving complexity of cytoplasmic structure.
AB  - Our knowledge of the structure of the cytoplasm has grown with the advent of
      advanced techniques and equipment that have allowed us to study cellular
      components. Over the past 150 years, such advances have steadily improved our
      realization of the complexity of cytoplasmic organization.

PMID- 11994749
TI  - Evolutionary conservation of microtubule-capture mechanisms.
AB  - The dynamic nature of microtubules allows them to search the three-dimensional
      space of the cell. But what are they looking for? During cellular morphogenesis,
      microtubules are captured at sites just under the plasma membrane, and this
      polarizes the microtubule array and associated organelles. Recent data indicate
      that the signalling pathways that are involved in regulating the different
      microtubule cortical interactions are not only conserved between species, but
      also that they function in diverse processes.

PMID- 11994750
TI  - The molecular basis of CaMKII function in synaptic and behavioural memory.
AB  - Long-term potentiation (LTP) in the CA1 region of the hippocampus has been the
      primary model by which to study the cellular and molecular basis of memory.
      Calcium/calmodulin-dependent protein kinase II (CaMKII) is necessary for LTP
      induction, is persistently activated by stimuli that elicit LTP, and can, by
      itself, enhance the efficacy of synaptic transmission. The analysis of CaMKII
      autophosphorylation and dephosphorylation indicates that this kinase could serve
      as a molecular switch that is capable of long-term memory storage. Consistent
      with such a role, mutations that prevent persistent activation of CaMKII block
      LTP, experience-dependent plasticity and behavioural memory. These results make
      CaMKII a leading candidate in the search for the molecular basis of memory.

PMID- 11994751
TI  - Through the eye, slowly: delays and localization errors in the visual system.
AB  - Reviews on the visual system generally praise its amazing performance. Here we
      deal with its biggest weakness: sluggishness. Inherent delays lead to
      mislocalization when things move or, more generally, when things change. Errors
      in time translate into spatial errors when we pursue a moving object, when we try
      to localize a target that appears just before a gaze shift, or when we compare
      the position of a flashed target with the instantaneous position of a
      continuously moving one (or one that appears to be moving even though no change
      occurs in the retinal image). Studying such diverse errors might rekindle our
      thinking about how the brain copes with real-time changes in the world.

PMID- 11994752
TI  - Control of goal-directed and stimulus-driven attention in the brain.
AB  - We review evidence for partially segregated networks of brain areas that carry
      out different attentional functions. One system, which includes parts of the
      intraparietal cortex and superior frontal cortex, is involved in preparing and
      applying goal-directed (top-down) selection for stimuli and responses. This
      system is also modulated by the detection of stimuli. The other system, which
      includes the temporoparietal cortex and inferior frontal cortex, and is largely
      lateralized to the right hemisphere, is not involved in top-down selection.
      Instead, this system is specialized for the detection of behaviourally relevant
      stimuli, particularly when they are salient or unexpected. This ventral
      frontoparietal network works as a 'circuit breaker' for the dorsal system,
      directing attention to salient events. Both attentional systems interact during
      normal vision, and both are disrupted in unilateral spatial neglect.

PMID- 11994753
TI  - Innate immunity: the missing link in neuroprotection and neurodegeneration?
AB  - Innate immunity was previously thought to be a nonspecific immunological
      programme that was engaged by peripheral organs to maintain homeostasis after
      stress and injury. Emerging evidence indicates that this highly organized
      response also takes place in the central nervous system. Through the recognition
      of neuronal fingerprints, the long-term induction of the innate immune response
      and its transition to an adaptive form might be central to the pathophysiology
      and aetiology of neurodegenerative disorders. Paradoxically, this response also
      protects neurons by favouring remyelination and trophic support afforded by glial
      cells.

PMID- 11994754
TI  - New treatments in neurorehabilitation founded on basic research.
AB  - Recent discoveries about how the central nervous system responds to injury and
      how patients reacquire lost behaviours by training have yielded promising new
      therapies for neurorehabilitation. Until recently, this field had been largely
      static, but the current melding of basic behavioural science with neuroscience
      promises entirely new approaches to improving behavioural, perceptual and
      cognitive capabilities after neurological damage. Studies of phenomena such as
      cortical reorganization after a lesion, central nervous system repair, and the
      substantial enhancement of extremity use and linguistic function by behavioural
      therapy, support this emerging view. The ongoing changes in rehabilitation
      strategies might well amount to an impending paradigm shift in this field.

PMID- 11994755
TI  - Modelling neurodegenerative diseases in Drosophila: a fruitful approach?
AB  - Human neurodegenerative diseases are characterized by the progressive loss of
      specific neuronal populations, resulting in substantial disability and early
      death. The identification of causative single-gene mutations in families with
      inherited neurodegenerative disorders has facilitated the modelling of these
      diseases in experimental organisms, including the fruitfly Drosophila
      melanogaster. Many neurodegenerative diseases have now been successfully modelled
      in Drosophila, and genetic analysis is under way in each of these models. Using
      fruitfly genetics to define the molecular pathways that underlie the
      neurodegenerative process is likely to improve substantially our understanding of
      the pathogenesis of the human diseases, and to provide new therapeutic targets.

PMID- 11994756
TI  - The problem of functional localization in the human brain.
AB  - Functional imaging gives us increasingly detailed information about the location
      of brain activity. To use this information, we need a clear conception of the
      meaning of location data. Here, we review methods for reporting location in
      functional imaging and discuss the problems that arise from the great variability
      in brain anatomy between individuals. These problems cause uncertainty in
      localization, which limits the effective resolution of functional imaging,
      especially for brain areas involved in higher cognitive function.

PMID- 11994757
TI  - Adjuvant and neoadjuvant radiotherapy and concurrent radiochemotherapy for rectal
      cancer.
AB  - Radical surgery with negative margins remains the most important prognostic
      factor in the treatment of rectal cancer. Combined modality treatment is the
      recommended standard adjuvant therapy for patients with locally advanced rectal
      cancer in the USA and in Germany. During the last decade substantial progress has
      been made in treatment modalities: surgical management currently includes a broad
      spectrum of operative procedures ranging from radical operations to innovative
      sphincter-preserving techniques. Specialized groups have reported excellent local
      control rates with total mesorectal excision (TME) alone. New and improved
      radiation techniques (conformal radiotherapy, intraoperative radiotherapy) and
      innovative schedules (protracted intravenous infusion, chronomodulated infusion)
      and combinations (oxaliplatin, irinotecan) of chemotherapy may have the potential
      to further increase the therapeutic benefit of adjuvant treatment. Moreover, the
      basic issue of timing of radio-(chemo-)therapy - preoperative versus
      postoperative - within a multimodality regimen is currently being addressed in
      prospective trials. Evidently, the current monolithic approaches, established by
      studies conducted more than a decade ago, to apply either the same schedule of
      postoperative radiochemotherapy to all patients with stage II/III rectal cancer
      or to give preoperative intensive short-course radiation according to the Swedish
      concept for all patients with resectable rectal cancer irrespective of tumor
      stage and treatment goal (e.g. sphincter preservation), need to be questioned.
      This review will discuss different irradiation settings in more recent and
      ongoing studies of perioperative radiotherapy for rectal cancer and will focus on
      the issue which patient should receive radiotherapy at all, and if so, how and
      when?

PMID- 11994758
TI  - Arginine catabolism, liver extracts and cancer.
AB  - Although it is self evident that cells will not grow in amino acid deficient
      medium, an observation less well appreciated is that malignant cells are
      particularly vulnerable to such deprivation, which can lead to their rapid
      demise. Indeed, the more flagrantly malignant the phenotype (anaplastic the
      tumor), the more susceptible the cells seem to be to deprivation. While some
      attempts to employ this strategy in cancer treatment have been made, the
      difference between normal and malignant cells should be more fully exploited as a
      means of selectively eliminating tumor cell populations. To be successful,
      information on differences between the normal and the deranged cell cycle engine
      and checkpoints, especially how these are affected by deprivation, is of crucial
      importance. Since it is only recently that the controls at restriction points
      have been elucidated, it is little surprise that earlier attempts to control
      tumor cell growth by limiting the availability of an essential amino acid have
      met with limited success. Studies have been sporadic and isolated, often with
      little more than anecdotal descriptions as far as clinical work was concerned.
      This review concentrates on what has been accomplished primarily in vitro and
      since about 1950 with regard to arginine catabolism, while recognising that other
      essential amino acids have also been the focus of attention by some
      investigators. Treatments have included medium and plasma manipulation, dietary
      control, enzymatic degradation, and the use of liver extracts. On some occasions,
      substitution of amino acid analogues has been explored. It is argued that current
      knowledge, combined with past experience, calls for a much closer examination of
      the full potential of amino acid (and specifically arginine) deprivation as a
      means of controlling tumor growth, with greater attention to protocols that might
      be used to treat human cancers.

PMID- 11994759
TI  - Down regulation of bcl2 expression in invasive ductal carcinomas is both estrogen
      and progesterone-receptor dependent and associated with poor prognostic factors.
AB  - In normal breast, Bcl2 is expressed in the non-pregnant and non-involuting
      mammary epithelium. The exact mechanism and the effect of the down regulation of
      the Bcl2 expression on breast cancer cells are not clearly defined. We compared
      down regulation as well as the persistent expression of Bcl2 with ER, PR, p53,
      and c-erb-B2 overexpression and clinicopathologic variables, and tumor stage in
      11 cases of ductal carcinomas in situ (DCIS) and 44 cases of invasive ductal
      carcinomas (IDC) of Korean women by immunohistochemical studies. Bcl2 down
      regulation was found in 39% of IDC and in 18% of DCIS cases. In IDC, while
      persistent Bcl2 expression was displayed in 95% and 78.9% of ER and PR
      immunoreactive ones and 71.9 % of c-erb-B2 immunonegative ones. Seventeen cases
      of Bcl2 down regulated IDC had a significant correlation with ER negativity
      (94.1%), PR negativity, (76.5%), and high nuclear (61.1% is grade III) and
      histological grade (76% is grade III). However, in DCIS, no significant
      correlation between the Bcl2 expression and various parameters were obtained,
      probably due to small sample size. In conclusion, the Bcl2 expression was both ER
      and PR dependent and down regulation of Bcl2 in IDC was significantly correlated
      with poor prognostic factors.

PMID- 11994760
TI  - Kaposi's sarcoma: clinico-pathological analysis of human immunodeficiency virus
      (HIV) and non-HIV associated cases.
AB  - Kaposi s sarcoma (KS) is a angioformative lesion that classically occurs in
      elderly Eastern European and Mediterranean males but is also common in
      immunosuppressed individuals particularly human immunodeficiency virus (HIV)
      infected patients. This study investigates the clinical and histopathological
      features of 47 patients with Kaposi s sarcoma from a teaching hospital in Sydney,
      Australia, in which 44 cases had adequate clinical follow-up information over a
      10-year period. Most of the lesions were of late stage (37/47 cases; 79%),
      consisting of 11 cases of plaque stage KS and 26 cases of nodular stage KS with
      only 10 cases of early or patch stage KS. The majority of the HIV-positive cases
      (23/33; 70%) and all of the HIV-negative (14/14; 100%) cases had late stage
      lesions (p=0.020; X 2 -test). The histopathological features that were more
      common in the KS lesions of HIV-negative patients were lesional cell mitosis
      (p=0.0002), single cell necrosis (p=0.001), apoptosis (p=0.0001) and single cell
      anaplasia (p=0.0001). The KS lesions in HIV-positive patients tended to have
      dissecting blood vessels (14/33 cases; 42%) unlike those seen in HIV-negative
      patients (0/14 cases; 0%) (p=0.004). Most HIV-positive cases (30/33; 90%) were
      males (p=0.0068); and all these patients (33/33 cases; 100%) were <60 years old,
      in contrast to HIV-negative patients (1/11 cases; 9%) (p=0.0001). HIV status does
      not affect the occurrence of multiplicity of KS lesions. However, extracutaneous
      or visceral KS lesions were more likely to occur in HIV-positive patients
      (p=0.027). The number of cases of histologically proven KS cases has decreased
      markedly over the recent 5 year period of 1995-1999 (n=14), which was less than
      half of the number of the preceding 5 year period, 1990-1994 (n=33). In summary,
      there are distinct differences in the clinical and histopathological features of
      Kaposi s sarcoma lesions in HIV-positive and HIV-negative patients. Despite the
      recent discovery of the HHV8 virus as the initiating and promoting factor of most
      of the KS lesions, these differences indicated that there might be different
      mechanisms that occur in HIV-positive and HIV-negative patients in the
      development of this lesion.

PMID- 11994761
TI  - CD44 variant exons in leukemia and lymphoma.
AB  - CD44 is a cell surface glycoprotein expressed on different cell types that
      functions in lymphocyte activation and homing, extracellular matrix adhesion and
      cellular migration. CD44 is encoded by a single gene composed of at least 20
      exons. The standard CD44 protein (CD44S or CD44H) is the hematopoietic form of
      CD44 in lymphoid cells. Variant isoforms (designated from v1 to v10) are formed
      by addition of new exons to the extracellular domain. High levels of CD44v6
      expression has been observed in some tumors and are associated with metastatic
      spread. The aim of the present study was to investigate and evaluate expression
      of the CD44v6 and v6-containing variants as a possible marker in chronic myeloid
      leukemia and lymphoma by reverse transcription-polymerase chain reaction. CD44
      exon v6 was detected in all patients and all individuals in the control group.
      CD44v6-v10 mRNA was observed in 25 patients but in none of the subjects in the
      control group. CD44v6/v9-10, CD44v6-v7, CD44v6/v10 transcripts were detected in
      11, 6, and 2 patients, respectively. CD44v6-7/v9-10 transcripts were not observed
      in either the patients or the healthy individuals. We conclude that CD44v6-v10
      expression may be associated with hematologic malignancies.

PMID- 11994762
TI  - The role of ultraviolet-B in corneal healing following excimer laser in situ
      keratomileusis.
AB  - Corneal photoablation with the 193 nm argon fluoride excimer laser during
      photorefractive keratectomy (PRK) in high diopter range is frequently associated
      with subepithelial haze and consequent refractive regression due to avascular
      corneal wound healing. The wound healing response can be augmented by Ultraviolet
      B (UV-B) exposure originating from sun or solarium. Clinically Laser in situ
      Keratomileusis (LASIK) even in high diopter range is associated with less
      subepithelial haze and regression than PRK. In an animal model, the morphologic
      changes of the rabbit cornea were evaluated following LASIK and secondary UV-B
      exposure. Light microscpic changes were found to be insignificant. Transmission
      electron microscopy (TEM) normal epithelium, epithelial adhesion structures and
      normal anterior stroma showed in the LASIK treated UV-B irradiated rabbit eyes.
      Around the peripheral LASIK cut, migrating keratocytes with pseudopodia were
      observed. Under the flap (160 microm depth) the overall stromal collagen
      structure was normal, some activated keratocytes and mild extracellular matrix
      formation within and around keratocytes were noted. Within activated keratocytes
      TEM showed prominent rough endoplasmic reticulum, Golgi apparatus, mitochondria
      and extracellular vacuoles, which showed resolution with time. These changes were
      much milder than in PRK treated-UV-B irradiated eyes. Secondary UV-B caused no
      long-term disturbance in corneal transparency in LASIK and UV-B treated rabbit
      eyes.

PMID- 11994763
TI  - Effect of sulfated beta-cyclodextrin, a water soluble cycloamylose, on the
      promotion and/or inhibition of angiogenesis.
AB  - Previous studies have reported that sulfated b b-cyclodextrin, a naturally
      occurring cycloamylose built up from six to eight glucopyranose units, when
      administered alone promotes angiogenesis, but administered with an angiostatic
      steroid inhibits angiogenesis in the cick embryo bioassay. In our experiments
      sulfated b b-cyclodextrin has been shown to possess many properties unrelated to
      its classical functions in the promotion and inhibition of angiogenesis that were
      not previously described. We studied the angiogenic and angiostatic properties of
      b b-cyclodextrin in a subcutaneous plastic sponge model in mice. We realized two
      set of experiments. In each set mice were randomized into five groups (n= 5
      mice). The first group was treated with sulfated b b-cyclodextrin (200 ng), the
      second group was treated with sulfated b b-cyclodextrin (2000 ng), the third
      group received unsubstituted b b-cyclodextrin (2000 ng), the fourth group was
      treated with sulfated b b-cyclodextrin (20000 ng) and the last group was used as
      a control group. In all groups compounds were administered intraperitoneally 4
      days after subcutaneous implantation of a sterile polyvinyl sponge on day 0,
      controls were not treated. Cyclodextrin administered alone at low drug
      concentration (200 ng) promoted angiogenesis and increased the development of
      venules in the sponge matrix. However, cyclodextrin administered at high drug
      concentration (2000 and 20 000 ng) reduced the vessel index in the sponge and
      areas of microhemorrhages were observed. From our results we propose that b b
      cyclodextrin contains both a promoter and an inhibitor of angiogenesis and that
      the activation of both is drug concentration dependent.

PMID- 11994764
TI  - Results of ovary tumor treatment with abdominally administered (198)Au evaluated
      on the basis of long term follow up.
AB  - In the period between 1959 and 1980 165 patients previously operated with ovarian
      tumor were treated by intraperitoneally administered (198)Au in the
      Oncoradiological Centre of the Uzsoki Hospital. The stage distribution of the 158
      patients with common epithelial histology was as it follows: Stage I/A 31; Stage
      I/B 9; Stage I/C 59; Stage II/A 19; Stage II/B 11; Stage II/C 7, Stage III/A 22.
      The five year survival result is the next: Stage I/A 90%; Stage I/B 78%; Stage
      I/C 58%; Stage II/A 26%; Stage II/B 27%; Stage II/C 14%; Stage III/A 18%. From
      the other 7 patients six had sex cord tumor and one lipid cell tumor. The number
      of the side effects is in good agreement with the data in literature. The use of
      (198)Au for intraperitoneal treatment of ovary tumors is not contemporary today
      because of gamma radiation of radiogold, but intraperitoneal radiation treatment
      should not be forgotten.

PMID- 11994765
TI  - HLA-DQBl alleles and susceptibility to cervical squamous cell carcinoma in
      Southern Iranian patients.
AB  - The association of HLA class II with various autoimmune diseases has been
      extensively investigated. Despite the importance and functions of HLA genes in
      the evolution of cancer, the allele specific association of HLA molecules in
      cancer patients has not been well investigated. In this study the HLA-class II
      alleles frequency was investigated in Iranian patients with cervical squamous
      cell carcinoma. HLA typing was carried out by PCR amplification using sequence
      specific primers (PCR-SSP). DRB1, DQA1 and DQB1 typing was performed for 23
      patients. The allele frequencies were calculated and compared with 36 healthy
      Iranian female controls. A positive association was observed between the
      existence of HLA-DQB1* 0601 and squamous cell carcinoma of the cervix (p<0.04,
      RR=1.94). Moreover, analysis of HLA-DRB1, DQA1 and DQB1 haplotypes indicated that
      none of the putative haplotypes were significantly associated with either patient
      or control group. Positive association of cervical carcinoma with a single allele
      of HLA-DQ provides evidence on the importance of HLA class II molecules and the
      immune response in squamous cell carcinoma of cervix.

PMID- 11994766
TI  - Large-scale pathology-based cancer data--a reflection of population-based cancer
      data.
AB  - Pathology-based cancer data is a high quality reflection of the patterns of
      cancer in the population it represents, provided the demographic details of the
      patients are carefully recorded. Relative frequency data is neither a replacement
      for population-based data nor a suggested alternative; it simply enhances the
      quality of population data and in very large data sets reflects the cancer
      patterns observed in the representative populations. Aware of the standard
      shortfalls of pathology-based data, the department of pathology,  The Aga Khan
      University Hospital  (AKUH) standardized its data, representing 53.4% of the
      cancer data of Karachi Division (Pakistan) and also reflecting the cancer pattern
      of other provinces of Pakistan. This data was compared with 4 different
      population and institutional-based data sets. The findings substantiate the
      observation that  despite the problems of interpretation of data from pathology
      laboratories, they are an invaluable source of information on cancer patterns in
      much of the world where incidence data are unavailable . If developing countries,
      unable to organize National Population- Based Registry should as an alternate
      develop National Pathology-based Registers a well targeted and monitored, a
      Cancer Control Program would be possible. A good quality, large-scale pathology
      data with demographic details of the patient recorded can also be extended to
      give coverage to the population.

PMID- 11994767
TI  - The image pyramid system--an unbiased, inexpensive and broadly accessible method
      of telepathology.
AB  - Although computerised information technology, including the Internet is broadly
      used and globally accessible it is still not a significant form of professional
      communications in diagnostic histopathology. The high cost of interactive dynamic
      telepathology systems makes their use limited outside the richest economies. In
      contrast static telepathology systems are relatively cheap but in practice their
      information content can be heavily biased by the choice of images sent by the
      consulting pathologist. The degree of this bias may be regarded simply as the
      amount of information transferred to a remote location expressed as a percentage
      of the total information present in the histological sample. We refer to this as
      the percentage of explicit versus implicit information. Another major source of
      bias may be found in the information transmitted in written or verbal discussion
      with a remote consultant. We have developed a system of static telepathology, the
      image pyramid, which attempts to minimise bias by transferring all of the
      information in a section to the consultant. It is inexpensive and should prove to
      be widely accessible.

PMID- 11994768
TI  - "Revertant" mammary solid papillary carcinoma in lymph node metastasis.
AB  - A case of invasive carcinoma of mixed papillary and not otherwise specified
      ductal type with areas of solid papillary ductal carcinoma in situ(DCIS) is
      reported. The solid papillary areas were predominantly of low nuclear grade, but
      a small area of intermediate-grade solid papillary neoplasm was also seen within
      the tumor, together with an area suggestive of microinvasion. The massive
      regional nodal tumor load consisted of invasive papillary carcinoma and revertant
      low-grade solid papillary carcinoma with no myoepithelial cells around the
      circumscribed solid papillary areas. This is the first report of a solid
      papillary pattern simulating intraductal carcinoma in lymph nodes, and the first
      time that a solid papillary carcinoma is reported in association with invasive
      papillary carcinoma. The case suggests that mammary carcinomas with a solid
      papillary pattern may sometimes be of higher grade than usual, and do not always
      represent a DCIS, but may be invasive.

PMID- 11994769
TI  - Another brick in the wall.

PMID- 11994770
TI  - What need is there for standardization of thyroid uptake or scintigraphy using
      99mTc pertechnetate in thyroid disease diagnosis?

PMID- 11994771
TI  - Familial cancer aggregation and the risk of lung cancer.
AB  - CONTEXT: Around 90% of lung cancer worldwide is attributable to cigarette
      smoking, although less than 20% of cigarette smokers develop lung cancer. Other
      factors such as diet, chronic lung diseases, occupation and possibly
      environmental agents also contribute to this cancer. Genetic factors seem to play
      a role in lung cancer, but the precise characteristics influencing lung cancer
      susceptibility are not known, since genetic factors are easily obscured by the
      strong environmental determinants of lung cancer, particularly smoking.
      OBJECTIVE: To estimate the effect that cancer occurrence among first-degree
      relatives has on the risk of lung cancer. DESIGN: Hospital-based case-control
      study. SETTING: The metropolitan region of Sao Paulo, Brazil. PARTICIPANTS: 334
      incident lung cancer cases and 578 controls matched by hospitals. MAIN
      MEASUREMENTS: By means of a structured questionnaire, cases and controls were
      interviewed about cancer occurrence in first-degree relatives, tobacco smoking,
      exposure to passive smoking, occupation, migration and socioeconomic status. Non
      conditional logistic regression was used to calculate the risk of familial cancer
      aggregation, the effect of cancer in first-degree relatives and smoking in
      conjunction, and for controlling confounders. RESULTS: The adjusted odds ratio
      (OR) revealed a slight, but not statistically significant, excess risk of lung
      cancer for subjects with a history of lung cancer in relatives (OR 1.21; 95%
      confidence interval [CI] 0.50 - 2.92). The same was found among those with a
      history of other tobacco-related cancers in relatives (OR 1.36; 95% CI 0.87 -
      2.14). A step gradient effect was observed regarding lung cancer risk, in
      accordance with increases in the number of pack-years of cigarette consumption.
      An interaction between familial cancer aggregation and tobacco smoking was
      detected. CONCLUSIONS: A mildly elevated risk of lung cancer among persons with a
      positive history of lung and other tobacco-related cancers was observed. The
      finding of an interaction between the variables of familial cancer aggregation
      and smoking suggests that familial cancer aggregation could be considered as a
      marker of susceptibility, increasing the risk of lung cancer among smokers. These
      results improve our knowledge of lung carcinogenesis and can guide future cancer
      genetic studies.

PMID- 11994772
TI  - Thyroid uptake and scintigraphy using 99mTc pertechnetate: standardization in
      normal individuals.
AB  - CONTEXT: Thyroid uptake and scintigraphy using 99mTc-pertechnetate has proven to
      be more advantageous than with 131I-iodide, since the images have better quality,
      the procedure is faster and the patient is submitted to a lower radiation dose.
      OBJECTIVE: The purpose of this study was to standardize a simple and fast
      methodology for performing thyroid uptake and scintigraphy and to determine the
      normal values for 99mTc- pertechnetate uptake. TYPE OF STUDY: Prospective, non
      randomized. SETTING: Division of Nuclear Medicine, Department of Radiology,
      School of Medical Sciences, Campinas State University. PARTICIPANTS: The study
      consisted of 47 normal individuals, 30 women and 17 men, with ages ranging from
      19 to 61 years (mean of 33 years). PROCEDURES: The laboratory assessment of
      thyroid function consisted of serum dosages of ultra-sensitive thyroxin and
      thyrotrophin. Twenty minutes after an intravenous injection of 10 mCi (370 MBq)
      of 99mTc-pertechnetate, the images were obtained on a computerized scintillation
      camera equipped with a low-energy high-resolution parallel hole collimator.
      RESULTS: All the individuals were euthyroid both on clinical and laboratory
      evaluation. The baseline thyroid 99mTc-pertechnetate uptake ranged from 0.4 to
      1.7%. The uptake values obtained in these normal individuals showed that 95%
      presented a thyroid uptake that ranged from 0.4 to 1.5% of the injected dose.
      CONCLUSION: The assessment of thyroid structure and function using 99mTc
      pertechnetate is a simple, fast and efficient method, which could easily become a
      part of the routine studies in nuclear medicine laboratories.

PMID- 11994773
TI  - Prevalence and determinants of erectile dysfunction in Santos, southeastern
      Brazil.
AB  - CONTEXT: Recent population-based surveys suggest that the prevalence of erectile
      dysfunction is between 30% and 56% among men over the age of 40. Most of these
      studies, however, are from the United States or Europe. We need estimates of
      erectile dysfunction from samples of Brazilian populations, as societies that
      differ ethnically, culturally, and economically may also differ with respect to
      potential risk factors for erectile dysfunction. OBJECTIVE: To determine the
      prevalence of erectile dysfunction and its potential correlates. SETTING: Santos,
      State of Sao Paulo. DESIGN: Cross-sectional study. PARTICIPANTS: A population
      based sample of men aged 40-70 years. Out of 718 men invited, 342 (47.6%)
      returned a completed questionnaire. MAIN MEASUREMENTS: Data on demographic
      variables, medical history, lifestyle habits and degree of erectile dysfunction.
      RESULTS: The prevalence of any degree of erectile dysfunction was 45.9% (minimal,
      33.9%; moderate, 8.5%; complete, 3.5%) and increased with age. In bivariate age
      adjusted analyses comparing men with no erectile dysfunction or minimal erectile
      dysfunction with those with moderate or complete erectile dysfunction, histories
      of diabetes or hypertension, depressive symptoms, heavy smoking and obesity were
      significantly associated with increased prevalence of erectile dysfunction,
      whereas moderate alcohol consumption was inversely associated with erectile
      dysfunction. In the multivariate model, age was a strong predictor of erectile
      dysfunction, while history of diabetes or hypertension and heavy smoking remained
      significantly associated with increased prevalence of erectile dysfunction.
      CONCLUSION: We found higher prevalence of erectile dysfunction (45.9%) among men
      older than 40 years old in Brazil. The variables associated with erectile
      dysfunction may alert physicians to patients who are at risk of erectile
      dysfunction as well as offer clues to the etiology of erectile dysfunction.
      Physicians should routinely ask their patients about sexual health and erectile
      dysfunction.

PMID- 11994774
TI  - ABO, Lewis, secretor and non-secretor phenotypes in patients infected or
      uninfected by the Helicobacter pylori bacillus.
AB  - CONTEXT: Epidemiological studies have demonstrated higher frequencies of the O
      blood group and the non-secretor phenotype of ABH antigens among patients
      suffering from peptic ulcers. Since Helicobacter pylori has been established as
      the main etiological factor in this disease, controversies about the associations
      of the ABO and Lewis blood group phenotypes and secretor and non-secretor
      phenotypes in relation to susceptibility towards infection by this bacillus have
      been presented. OBJECTIVE: To verify the frequencies of ABO, Lewis blood group
      phenotypes, secretor and non-secretor phenotypes in patients infected or
      uninfected by H. pylori. DESIGN: Cross-sectional study. SETTING: Outpatient
      clinic. PARTICIPANTS: One hundred and twenty patients with dyspeptic symptoms who
      underwent endoscopy. MAIN MEASUREMENTS: ABO and Lewis blood group phenotypes were
      determined by a standard hemagglutination test and the secretor and non-secretor
      phenotypes were evaluated by saliva samples using the inhibitor hemagglutination
      test. RESULTS: The diagnosis of infection, made via breath and urea tests and
      confirmed using polymerase chain reaction (PCR) in gastric biopsy fragments,
      showed the presence of H. pylori in 61.7% of the patients and absence in 38.3%.
      The differences between the frequencies of the ABO blood group phenotypes among
      infected (A 27.0%; B 12.2%; AB 4.0% and O 56.8%) and uninfected patients (A
      58.7%; B 13.0%; AB 4.3% and O 24.0%) were significant. The Lewis blood type,
      secretor and non-secretor phenotypes showed homogeneous distribution between the
      groups of patients analyzed. CONCLUSIONS: Our results suggest that the infection
      of H. pylori can be related to ABO blood groups but not to the Lewis blood group
      nor to secretor and non-secretor phenotypes.

PMID- 11994775
TI  - Acute abdomen due to late retroperitoneal extravasation from a femoral venous
      catheter in a newborn.
AB  - CONTEXT: The use of parenteral nutrition via a central venous catheter is a
      common practice in the neonatal intensive care setting. Extravasation of the
      infusate leading to an acute abdomen is a complication that has only rarely been
      documented. This report describes the case of a premature infant with a femoral
      catheter placed in the inferior vena cava, who developed an acute abdomen as a
      result of late retroperitoneal extravasation of parenteral nutrition. CASE
      REPORT: A pre-term infant receiving total parenteral nutrition via a femoral
      venous catheter developed an acute abdomen five days after the catheter
      placement. Extravascular catheter migration to the retroperitoneal space and
      extravasation of the infusate was diagnosed by contrast injection. Withdrawal of
      the catheter was followed by prompt cessation of the signs and full recovery from
      the acute abdomen, without the need for surgery. A review of the literature is
      presented, emphasizing the clinical and therapeutic aspects of this unusual
      complication from femoral venous catheterization and parenteral nutrition.

PMID- 11994776
TI  - CMV-DNA detection in patients with thrombocytopenia.

PMID- 11994777
TI  - To use or not to use dipyrone?

PMID- 11994778
TI  - A comparison of sensitivity of spirotox biotest with standard toxicity tests.
AB  - The Spirotox test utilizes a large ciliate protozoan, Spirostomum ambiguum, as a
      bioindicator. Two kinds of test responses were observed after 24 and 48 h of
      incubation: different deformations and lethal response. The toxicity of 78
      organic compounds evaluated by the Spirotox-volatile procedure varied over six
      orders of a magnitude from -log (24-h LC(50)) = -3.0 (methanol) to 3.0
      (pentachlorophenol). Deformations of the S. ambiguum were two to three times more
      sensitive toxic response than lethality. The sensitivity of the Spirotox test was
      compared to four bioassay systems used worldwide: Tetrahymena pyriformis,
      Microtox, Daphnia magna, and Pimephales promelas. The toxicants were sorted
      according to the mechanism of action. The toxicity data for both protozoa. T.
      pyriformis and S. ambiguum were almost identical. Microtox, D. magna, and P.
      promelas were in general six- to eightfold more sensitive than the 24-h LC(50)
      Spirotox. The best agreement of toxicity data appeared in the group of nonpolar
      narcotics. In contrast the toxicity data for all tests only slightly correlated
      for polar narcotics. Very low slope for polar narcotics indicates that the
      toxicity range was much broader for the Spirotox test comparing to the others.
      The most toxic polar narcotics were even more toxic to Spirotox than to Microtox,
      Daphnia, and fish.

PMID- 11994779
TI  - Bioaccumulation of PCBs in aquatic biota from a tidal freshwater marsh ecosystem.
AB  - Water, sediments, and aquatic biota were sampled in a tidal river-marsh on the
      Potomac River near Washington, DC (USA) to assess baseline concentrations of
      polychlorinated biphenyls (PCBs) and bioaccumulation in finish species. The mean
      sediment total-PCB concentration in the wetland was 50 ng/g dry weight, and mean
      concentrations in biota ranged from 150 ng/g to 450 ng/g wet weight. The highest
      PCB concentrations were observed in channel catfish. The median biota-sediment
      accumulation factor (BSAF) estimated in all finfish species for total-PCBs was
      2.9. However, some of the individual and co-eluting PCB congeners had median
      BSAFs that were substantially greater (e.g., congener numbers 42, 74,
      182/187/128, and 171) or lower (e.g., congener numbers 18/15, 45, 185, and 208)
      than the total-PCB average. Apparent bioaccumulation factors (biota/water PCB
      concentration ratios) for PCB congeners showed a parabolic relation with n
      octanol/water partition coefficients, confirming some previous investigations.
      There was no clear trend between apparent bioaccumulation factors and trophic
      level. Organic-carbon-normalized sediment distribution constants (sediment/water
      PCB concentration ratios) were linearly related to the apparent bioaccumulation
      factors for all the finfish species investigated.

PMID- 11994780
TI  - Mouthpart deformities and nucleolus activity in field-collected Chironomus
      riparius larvae.
AB  - Chironomid mouthpart deformities and aberrations of their polytenic chromosomes
      are sublethal responses to toxic stress. These endpoints have been used in
      several cases as bioindications for sediment pollution. In the present study we
      aimed to establish whether there was an association between mouthpart deformities
      and nucleolus activity in the polytenic chromosomes. Such information could be
      useful to gain insight into the mechanisms involved in the occurrence of
      mouthpart deformities and their consequences on the larvae. Third-instar larvae
      of Chironomus riparius were collected at a site downstream of a sewage treatment
      plant mostly contaminated by pesticides. Larvae were then raised in the
      laboratory in aquaria containing sediment and water from the study location.
      During a 16-day period, larvae ready to molt to the fourth instar were reared
      individually. Within a few hours of their molt, the larvae were preserved. The
      presence of mouthpart deformities (mentum, mandibles, and pecten epipharyngis)
      and the percentage of active nucleoli were assessed. Those larvae presenting
      mentum deformities had a significantly higher incidence of active nucleoli in
      their polytenic chromosomes than nondeformed larvae. Because a high number of
      active nucleoli generally indicates increased rRNA synthesis, deformed larvae
      seemed to exhibit a higher protein synthesis than normal individuals. The
      synthesis of additional proteins may increase deformed larva tolerance to
      toxicants.

PMID- 11994781
TI  - Heavy metals in green mussel (Perna viridis) and oysters (Crassostrea sp.) from
      Trinidad and Venezuela.
AB  - Heavy metal concentrations were monitored in edible soft tissues of shellfish
      from Trinidad and Venezuela. Oysters (Crassostrea sp.) and the green mussel
      (Perna viridis), which is a recently transplanted species to the Caribbean from
      the Far East, were collected at six locations in Venezuela and five in Trinidad,
      the latter along the coast line of the Gulf of Paria. Simple and low-cost methods
      of analysis were optimized and validated using standard reference materials.
      Cadmium, copper, lead, nickel, and zinc were analyzed by flame atomic absorption
      spectrometry. Mercury was determined by cold-vapor atomic absorption
      spectrometry. The present study has confirmed that oysters have a much greater
      capacity for accumulation of copper and zinc than does green mussel. In addition,
      concentrations of copper and zinc in oysters (Crassostrea sp.) at many of the
      sites in the Gulf of Paria exceeded local and international standards, whereas
      green mussel P. viridis contained generally acceptable levels for human
      consumption.

PMID- 11994782
TI  - Impaired Acroneuria sp. (Plecoptera, Perlidae) populations associated with
      aluminum contamination in neutral pH surface waters.
AB  - Our aim was to quantify impairment to invertebrate predator populations,
      particularly to Acroneuria sp. (Plecoptera, Perlidae), downstream of an acid mine
      drainage-impacted tributary to the North Fork of the Powell River, southwestern
      Virginia. Predatory insects comprised 9.0 +/- 1.3% of the total abundance at the
      three stations upstream of the impacted tributary, but were significantly reduced
      (p = 0.0039) downstream (3.9 +/- 0.6%). Acroneuria sp. populations followed the
      same trend, with the upstream average (2.3 and 2.8%) being significantly higher
      (p < 0.05) than the downstream averages (0.2 and 0%) during 1999 and 2000,
      respectively. Using correlation analysis, we evaluated the relationship between
      the percent abundance of Acroneuria sp. throughout this reach and metal
      concentrations in water, sediment, and biological tissues (invertebrate predators
      and primary consumers). Water column aluminum (Al) concentration was the only
      parameter that was significantly correlated with percent Acroneuria sp.
      abundance, with correlation coefficients of -0.845 and -0.873 during 1999 and
      2000, respectively. While this correlation exists, it may not indicate a causal
      relationship, and experiments should be conducted to determine the long-term
      toxicity of various Al species to perlid stoneflies.

PMID- 11994783
TI  - Impact of a commercial peat moss operation on water quality and biota in a small
      tributary of the Richibucto River, Kent County, New Brunswick, Canada.
AB  - The St-Charles Plain (Kent County, New Brunswick, Canada) commercial peat moss
      operation has been ongoing since 1983. To process the peat, a dry extraction
      method is used that requires extensive drainage of the peat bog. The water is
      directed toward sedimentation ponds, where it drains into a small brook, which
      feeds into a river affected by tidal salt water. Water discharge from the bog
      contains large amounts of peat particles that deposit in the surrounding
      watershed. As a result, the pH of the freshwater sites that receive the drainage
      water from the commercial operation, is fairly acidic (pH 3.9-4.7). Water samples
      from or near the peat moss operation have a higher concentration of total
      phosphorous and total organic carbon. The peat particles contain relatively high
      levels of total mercury, as reflected by analysis of peat sediments. However, the
      water samples contained low levels of dissolved mercury. Indigenous samples of
      biota-namely, sand shrimps (Crangon septemspinosa) and mummichogs (Fundulus
      heteroclitus)-did not contain mercury levels higher in the impacted sites than in
      the reference sites. Introduced blue mussels (Mytilus edulis) did not accumulate
      significant amounts of mercury during a 62-day exposure in the study area.
      Overall, the data suggest that although relatively large amounts of mercury
      containing peat particles are discharged into the ecosystem, bioaccumulation of
      mercury in the biota does not occur.

PMID- 11994784
TI  - Selenium in a Wyoming grassland community receiving wastewater from an in situ
      uranium mine.
AB  - Water, soil, vegetation, grasshoppers, bird eggs, and bird livers collected at a
      23.5-ha (58 acres) grassland irrigated with wastewater from an in situ uranium
      mine (study area) and a reference site in 1998 were analyzed for selenium and
      other trace elements. Selenium concentrations in the uranium mine wastewater
      applied onto the grassland ranged from 340 to 450 microg/L. Selenium in the upper
      15 cm (6 in) of soil from the irrigated grassland at the mine ranged from 2.6 to
      4.2 microg/g dry weight (DW). Mean selenium concentrations in soil and water were
      5 and 15 times higher at the study area than at the reference site. Selenium
      concentrations in grasses and grasshoppers ranged from 6.8 to 24 microg/g and 11
      to 20 microg/g DW, respectively. Selenium in red-winged blackbird eggs and livers
      collected from the study area ranged from 13.2 to 22 microg/g and 33 to 53
      microg/g DW, respectively, and concentrations were well in excess of toxic
      thresholds. Mean selenium concentrations in grasses, grasshoppers, and bird eggs
      and livers were 5.8 to 30 times higher at the study area than at the reference
      site. Elevated selenium concentrations in water, soil, grasshoppers, and red
      winged blackbird eggs and livers collected from the study area demonstrate that
      selenium is being mobilized and is bioaccumulating in the food chain.

PMID- 11994785
TI  - Synthetic musks in the environment. Part 1: Species-dependent bioaccumulation of
      polycyclic and nitro musk fragrances in freshwater fish and mussels.
AB  - Bioaccumulation of polycyclic musks (HHCB, AHTN) and nitro musks (musk xylene,
      musk ketone, and their amino metabolites) in aquatic biota was investigated by
      analyzing 18 fish samples (rudd, tench, crucian carp, eel) and 1 pooled zebra
      mussel sample from the pond of a municipal sewage treatment plant. Furthermore,
      water samples taken at the effluent of the sewage plant as well as water samples
      and two series of semipermeable membrane devices (SPMDs) from the pond were
      included. This comprehensive data set allowed the determination of species
      dependent bioaccumulation factors on a lipid basis (BAF(L)), e.g., for HHCB the
      BAF(L) in tench were more than 20 times higher than in eel. The BAF(L) for HHCB
      and AHTN in biota were lower than the partition coefficients K(SPMD/W) obtained
      from SPMD samples, which are assumed to represent model bioconcentration values.
      This stresses that metabolism of these compounds in fish must not be neglected.

PMID- 11994786
TI  - Synthetic musks in the environment. Part 2: Enantioselective transformation of
      the polycyclic musk fragrances HHCB, AHTN, AHDI, and ATII in freshwater fish.
AB  - A method for the enantioselective separation of the chiral polycyclic musks HHCB,
      AHTN, AHDI, and ATII is presented. Eighteen fish samples (rudd, tench, crucian
      carp, eel) and one pooled zebra mussel sample from the pond of a municipal sewage
      treatment plant were investigated with regard to their concentrations and the
      enantiomeric ratios (ERs) of polycyclic musks. In addition, three water samples
      taken at the effluent of the sewage plant, as well as two water samples and two
      series of semipermeable membrane devices (SPMDs) consisting of six samples each
      from the pond were included in the present study. This comprehensive data set
      allowed a reliable evaluation of species-dependent metabolization processes. The
      pattern of the polycyclic musks in the chromatograms obtained by enantioselective
      gas chromatography seems to be typical of each species, like a fingerprint. The
      highest deviations from the racemic ER were found for trans-HHCB and trans-ATII
      in crucian carp with values of or below 0.1. Calculations showed that
      enantioselective transformation seems to be the most important process, resulting
      in the observed lower concentrations in crucian carp compared to tench.
      Consequences for a risk assessment are discussed.

PMID- 11994787
TI  - Total mercury concentrations in lakes and fish of western Maryland, USA.
AB  - The purpose of this study was to quantify total mercury concentrations in three
      species of fish in three lakes of western Maryland: Piney Creek reservoir, Deep
      Creek Lake, and Lake Habeeb. We measured total mercury concentrations in water
      from each lake and muscle tissue from 119 fish collected in fall 2000: 15
      largemouth bass (Micropterus salmoides), 15 yellow perch (Perca flavescens), and
      15 bluegill (Lepomis macrochirus) from the Piney Creek reservoir; 15 largemouth
      bass, 15 yellow perch, and 14 bluegill from Deep Creek Lake; and 15 largemouth
      bass and 15 bluegill from Lake Habeeb. Average total mercury concentrations (+/-
      SD) in surface waters were 0.96 +/- 0.03 ng L(-1) for the Piney Creek reservoir,
      0.56 +/- 0.07 ng L(-1) for Deep Creek Lake, and 0.40 +/- 0.05 ng L(-1) for Lake
      Habeeb. These water quality differences were sometimes reflected in the total
      mercury concentration in fish muscle tissue. Total mercury concentrations in
      bluegill (0.05 +/- 0.02 microg g(-1)) and largemouth bass (0.10 +/- 0.03 microg
      g(-1)) from Lake Habeeb were significantly (p < 0.001) lower than the total
      mercury concentrations in bluegill and largemouth bass from the Piney Creek
      reservoir (bluegill: 0.13 +/- 0.04 microg g(-1) and largemouth bass: 0.37 +/-
      0.18 microg g(-1)) and Deep Creek Lake (bluegill: 0.11 +/- 0.04 microg g(-1) and
      largemouth bass: 0.30 +/- 0.09 microg g(-1)). Yellow perch from the Piney Creek
      reservoir had significantly higher total mercury concentrations than yellow perch
      from Deep Creek Lake (0.20 +/- 0.08 microg g(-1) versus 0.13 +/- 0.04 microg g(
      1)). In contrast, total mercury concentrations in largemouth bass from the Piney
      Creek reservoir and Deep Creek Lake were not significantly different. With the
      exception of largemouth bass from Lake Habeeb and yellow perch from Deep Creek
      Lake, there were relatively strong (r(2) > 0.39-0.79) log-log relationships
      between the size (weight and length) of the fish and total mercury concentrations
      in muscle tissue. The largest largemouth bass (> 800 g and > 38 cm) from both
      Deep Creek Lake and the Piney Creek reservoir had total mercury concentrations
      that exceeded the consumption advisory of 0.5 microg g(-1) that is used by many
      states and Canada. In contrast, total mercury concentrations in largemouth bass
      from Lake Habeeb did not exceed this consumption advisory. Our results suggest
      that fish consumption advisories are needed for largemouth bass in the Piney
      Creek reservoir and Deep Creek Lake.

PMID- 11994788
TI  - Effects of tetrachloroethylene on the viability and development of embryos of the
      Japanese medaka, Oryzias latipes.
AB  - We evaluated the acute toxicity of Tetrachloroethylene (C(2)Cl(4)), and
      investigated its sub-chronic effects on the embryonic development of Japanese
      medaka (Oryzias latipes). One-day-old eggs/embryos of this fish species were
      exposed, under static renewal conditions, to serial concentrations (0, 20, 40,
      60, and 80 mg/L) of C(2)Cl(4) for 96 h (acute) and 10 days (sub-chronic) time
      periods. The toxic endpoints evaluated included: egg/embryo viability,
      hatchability, and morphological/developmental abnormalities. The acute toxicity
      test resulted in a 96 h-LC(50) of 27.0 (19.5-32.9) mg/L for egg viability.
      Exposure of eggs to sub-chronic concentrations (0, 1.5, 3, 6, 12, and 25 mg/L) of
      C(2)Cl(4) significantly reduced hatchability and larval survival, in a
      concentration dependent manner. At the highest tested concentration (25 mg/L) of
      the sub-lethal exposure, larval survival was greatly reduced to within three days
      post-hatch. The lowest tested concentration (1.5 mg/L) produced a significant
      number of developmental effects to the Japanese medaka, including abnormal
      development of the circulatory system, yolk-sac edema, pericardial edema,
      scoliosis, hemorrhaging, blood pooling, and defects in heart morphology. The
      severity of these abnormalities was concentration-dependent. It can be concluded
      from these results that tetrachloroethylene is teratogenic to the Japanese
      medaka.

PMID- 11994789
TI  - Dietary exposure of finfish to aromatic contaminants and tissue distribution.
AB  - Large rainbow trout (400 g) were exposed to food pellets spiked with four
      polycyclic aromatic compounds (PACs). Muscle, liver, internal organs, fatty
      tissue, and blood were analyzed after 5, 10, 15, and 19 weeks for PAC, lipid, and
      moisture content. At all collection times, concentrations expressed on a per gram
      basis were higher in fatty tissue and internal organs, followed by liver and
      muscle, and lowest levels were observed in blood. When examining the tissue
      burden, the highest bioaccumulations of carbazole, dibenzofuran,
      dibenzothiophene, and fluorene were in muscle and internal organs, intermediate
      in fatty tissue, and lowest in blood and liver. Carbazole with the lowest log
      K(OW) showed the lowest concentration within any tissue. Levels in tissues were
      significantly correlated to log K(OW) (> 5% level of significance), especially
      with longer exposure, and were more highly correlated when examining muscle,
      fatty tissue, and internal organs (> 0.05%). Different tissues displayed
      different time trends, and ratios between organs help determine the length of
      exposure. The most striking change in levels observed with time was in internal
      organs relative to other tissues, particularly when compared to daily exposure.
      The elimination of contaminants in feces and gallbladder bile was also compared,
      because they represent additional tools to assess recent exposure.

PMID- 11994790
TI  - Effect of pyrene on hepatic cytochrome P450 1A (CYP1A) expression in Nile Tilapia
      (Oreochromis niloticus).
AB  - The effect of pyrene on the regulation of the gene expression of cytochrome
      P4501A ( CYP1A) was studied in tilapia (Oreochromis niloticus), a tropical fish
      of great ecological and economical importance. To evaluate CYP1A mRNA, tilapia
      CYP1A cDNA was cloned, sequenced, and compared with those CYP1A reported
      sequences in the GeneBank DNA database. The top seven matches corresponded to
      CYP1A from other teleosts. Hepatic CYP1A mRNA levels showed a significant
      increase at day 1 after pyrene injection (20 mg kg(-1) body weight [BW]), and
      this CYP1A mRNA levels did not return to basal levels for up to 5 days. The
      immunoblot analysis of CYP1A protein levels using polyclonal rabbit-anti-trout
      antibodies in the liver of pyrene-treated (20 mg kg(-1) BW) tilapias showed a 1.9
      fold increase at day 3 after injection. Ethoxyresorufin- O-deethylase (EROD)
      activity increased 18-fold with respect to control fish at day 3 after injection.
      CYP1A protein and EROD activity remained increased for 5 days after a single
      pyrene IP administration. Similarly, the highest concentration of 1-hydroxypyrene
      (1-OH pyrene) in bile was observed in fish sacrificed at day 3 after injection.
      EROD activity and 1-OH pyrene concentration showed a statistically significant
      correlation (r = 0.85) according to the Spearman test, suggesting the
      participation of this cytochrome in the biotransformation of pyrene.

PMID- 11994791
TI  - PCDDs/PCDFs, PCBs, and organochlorine pesticides in eggs of Eurasian sparrowhawks
      (Accipiter nisus), hobbies (Falco subbuteo), and northern goshawks (Accipiter
      gentilis) collected in the area of Berlin-Brandenburg, Germany.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and organochlorine (OC)
      pesticides were measured in unsuccessfully hatched eggs of three different kinds
      of predatory birds: 3 eggs of sparrowhawks, 7 eggs of hobbies, and 16 eggs of
      goshawks collected in the German region of Berlin-Brandenburg. Using toxic
      equivalency factors for birds, eggs of hobbies contained mean concentrations of
      478 pg TEQ/g fat and 551 pg TEQ/g fat contributed by PCDD/Fs and coplanar PCBs,
      respectively. For sparrowhawks the respective TCDD equivalents were 424 and 1278
      pg/g fat; those for goshawks were 211 and 935 pg/g fat. The mean value of the
      summed concentrations of the PCB congeners 28, 52, 101, 138, 153, and 180
      amounted to 11 microg/g fat in eggs of hobbies, 9.5 microg/g fat for
      sparrowhawks, and 16.1 microg/g fat for goshawks. Of the analyzed organochlorine
      pesticides the concentration of p,p'-DDE was highest (up to 273 microg/g); the
      concentration of the other OCs, with the exception of methoxychlor in eggs of
      goshawks (highest level of 10.6 microg/g fat), were negligible. In all cases the
      calculated toxicity of the coplanar PCBs surpassed the toxicity of the PCDD/Fs,
      at least by a factor of two. Due to the higher concentration of the coplanar PCB
      77 compared to PCB 126 in eggs of hobbies, it is concluded that its metabolic
      excretion in this species is much lower than in sparrowhawks and goshawks.

PMID- 11994792
TI  - Bioaccumulation of organochlorine contaminants in bowhead whales (Balaena
      mysticetus) from Barrow, Alaska.
AB  - Bowhead whale (Balaena mysticetus) blubber (n = 72) and liver (n = 23) samples
      were collected during seven consecutive subsistence harvests (1997-2000) at
      Barrow, Alaska, to investigate the bioaccumulation of organochlorine contaminants
      (OCs) by this long-lived mysticete. The rank order of OC group concentrations
      (geometric mean, wet weight) in bowhead blubber samples were toxaphene (TOX; 455
      ng/g) > polychlorinated biphenyls (SigmaPCBs; 410 ng/g) >
      dichlorodiphenyltrichloroethane-related compounds (SigmaDDT; 331 ng/g) >or=
      hexachlorocyclohexane isomers (SigmaHCHs; 203 ng/g) >or= chlordanes and related
      isomers (SigmaCHLOR; 183 ng/g) > chlorobenzenes (SigmaCIBz; 106 ng/g). In liver,
      SigmaHCH (9.5 ng/g; wet weight) was the most abundant SigmaOC group, followed by
      SigmaPCBs (9.1 ng/g) >or= TOX (8.8 ng/g) > SigmaCHLOR (5.5 ng/g) > SigmaCIBz (4.2
      ng/g) >or= SigmaDDT (3.7 ng/g). The dominant analyte in blubber and liver was
      p,p'-DDE and alpha-HCH, respectively. Total TOX, SigmaPCBs, SigmaDDT, and
      SigmaCHLOR concentrations in blubber generally increased with age of male whales
      (as interpreted by body length), but this relationship was not significant for
      adult female whales. Biomagnification factor (BMF) values (0.1-45.5) for OCs from
      zooplankton (Calanus sp.) to bowhead whale were consistent with findings for
      other mysticetes. Tissue-specific differences in OC patterns in blubber and liver
      may be attributed to variation of tissue composition and the relatively low
      capacity of this species to biotransform various OCs. Principal component
      analysis of contaminants levels in bowhead blubber samples suggest that
      proportions of OCs, such as beta-HCH, fluctuate with seasonal migration of this
      species between the Bering, Chukchi, and Beaufort Seas.

PMID- 11994793
TI  - Intercomparison studies on distribution and coassociations of heavy metals in
      liver, kidney, and muscle of harbor porpoise, Phocoena phocoena, from southern
      Baltic Sea and coastal waters of Denmark and Greenland.
AB  - The concentrations of selected metals such as Cd, Pb, Cu, Zn, Cr, Ni, Mn, and Fe
      were determined in liver, kidney, and muscle of harbor porpoise (Phocoena
      phocoena) from three geographical regions, i.e., the Baltic Sea and Danish and
      Greenland coastal waters. The concentrations of Cd in liver and kidney increased
      with age of the specimens analyzed. Significant interspatial variations in both
      hepatic and renal levels of Cd were also observed. Average hepatic levels of Cd
      in Baltic, Danish, and Greenland specimens were (age range) 0.05-0.09, 0.12-0.25,
      and 20.6-51.6 microg g(-1) dry weight, respectively. Such values for renal Cd
      were as follows: 0.55-0.71, 0.14-1.84, and 0.55-94.3 microg g(-1) dry weight. In
      contrast to Cd, concentrations of Cu in the liver and kidney of specimens from
      Baltic, Danish, and Greenland areas did not indicate such great interspatial
      variability. The average hepatic values amounted to (age range) 14.1-15.5, 22.1
      63.6, and 16.3-25.9 microg g(-1) dry weight, and kidney contained on the average
      7.83-8.80, 11.7-16.2, and 11.1-15.7 microg Cu g(-1) dry weight, respectively. The
      higher levels of hepatic and renal Cd in Greenland specimens than in Baltic ones
      could be explained by different food composition in the area studied. Baltic
      porpoises mainly feed on fish (cod, plaice) containing extremely low levels of
      muscle Cd, but an important diet component of Greenlandic individuals is squid,
      characterized by elevated levels of Cd.

PMID- 11994794
TI  - Examination of the contaminants and performance of animals fed and bedded using
      de-inking paper sludge.
AB  - In the noncereal-producing areas, there is not enough straw to supply the amount
      required for animal bedding. However, pulp and paper mills produce tons of wood
      fiber wastes, including de-inking paper sludge (DPS), in which most toxic
      compounds are at their detection limit. Among the detected compounds in DPS,
      aluminum, copper, and polycyclic aromatic hydrocarbons (PAHs) are present and
      were selected as model molecules. In this context, broilers were submitted to a
      diet containing 0, 5, and 10% of their ration as DPS. In addition, broilers and
      pigs were grown on de-inking paper sludge and wood shavings beddings. The
      presence of aluminum and copper were evaluated in blood and bones, whereas the
      presence of PAHs was evaluated in fat, liver, meat, and urine or blood of
      broilers and pigs. Animal performances were also investigated. DPS bedding did
      not increase aluminum or copper contents of blood or bones or PAHs in animal
      tissues. Animal performances and health were similar on DPS and wood shaving
      beddings. Using DPS as bedding material provides an integrated source of disposal
      of DPS and animal manure.

PMID- 11994795
TI  - Quantitative analysis of the relative effectiveness of 3 iliotibial band
      stretches.
AB  - OBJECTIVE: To compare the relative effectiveness of 3 common standing stretches
      for the iliotibial band (ITB): arms at side (stretch A), arms extending overhead
      (stretch B), and arms reaching diagonally downward (stretch C). DESIGN: Each
      subject's biomechanics was captured as a 3-dimensional image by using a 4-camera
      gait acquisition system with a forceplate. SETTING: University biomotion
      laboratory. PARTICIPANTS: Five male elite-level distance runners. INTERVENTIONS:
      All participants performed each of the 3 standing stretches for the ITB. MAIN
      OUTCOME MEASURES: For each stretch, change in ITB tissue length and the force
      generated within the stretched complex was measured. Data were then combined and
      analyzed by using kinetic values assessment. RESULTS: All 3 stretches created
      statistically significant changes in ITB length (P<.05), but stretch B,
      incorporating overhead arm extension, was consistently most effective both for
      average ITB length change and average adduction moments at the hip and knee.
      CONCLUSIONS: Adding an overhead arm extension to the most common standing ITB
      stretch may increase average ITB length change and average external adduction
      moments in elite-level distance runners.

PMID- 11994796
TI  - Suprascapular nerve block for pain relief in adhesive capsulitis: comparison of 2
      different techniques.
AB  - OBJECTIVE: To evaluate the clinical effectiveness of 2 suprascapular nerve block
      techniques in adhesive capsulitis. DESIGN: A single-blinded, randomized,
      comparative clinical trial. SETTING: Physical medicine and rehabilitation
      department of a university hospital in Turkey. PARTICIPANTS: Forty-one patients
      with adhesive capsulitis. INTERVENTIONS: Suprascapular nerve block with patients
      randomly divided into 2 groups: group A, needle tip guided by superficial bony
      landmarks, or group B, near-nerve electromyographically guided technique. MAIN
      OUTCOME MEASURES: Visual analog scale (VAS) score for pain severity and range of
      motion (ROM) were assessed before the injection and at 10 and 60 minutes after
      it. RESULTS: Active and passive ROM changes and VAS score changes from baseline
      were statistically significant for each group (P<.05). Passive ROM changes within
      time after the injection were statistically significant between the 2 groups in
      all planes except glenohumeral abduction. Achieved VAS score changes in the
      groups within time were significantly different from each other (P=.001). The VAS
      score difference after the suprascapular nerve block was more prominent in the
      near-nerve electromyography group. CONCLUSION: The near-nerve electromyography
      technique for suprascapular nerve block was more successful in providing and
      maintaining pain relief for up to 60 minutes.

PMID- 11994797
TI  - Community-based referrals for electrodiagnostic studies in patients with possible
      carpal tunnel syndrome: what is the diagnosis?
AB  - OBJECTIVES: To determine what proportion of patients referred with a clinical
      suspicion of carpal tunnel syndrome (CTS) have negative electrodiagnostic studies
      and identify their clinical diagnoses and to identify clinical features that
      predict the outcome of electrodiagnostic testing in patients referred with
      suspected CTS. DESIGN: Retrospective review of patients consecutively referred to
      the electrodiagnostic center with suspected CTS over a 1-year period. SETTING:
      Community-based electrodiagnostic center. PARTICIPANTS: Three hundred forty-eight
      patients with suspected CTS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      The diagnosis of CTS was based on the electrodiagnostic findings. RESULTS: Of the
      348 patients enrolled, 179 (51.4%) had electrodiagnostic studies that were
      inconsistent with a diagnosis of CTS. Twenty-seven patients (15.1%) had other
      electrodiagnostic abnormalities (eg, ulnar neuropathy, cervical radiculopathy),
      whereas the remaining 152 (84.9%) patients had studies within normal limits.
      Seventy-one patients (46.7%) with normal studies were diagnosed with
      musculoskeletal disorders, with myofascial pain and musculotendinous strain being
      most common. By using a multiple logistic regression model, clinical variables
      that may predict the outcome of electrodiagnostic testing for CTS included
      gender, duration of symptoms, nocturnal symptoms, sensory symptoms, wrist pain,
      neck pain, pinprick sensation, abductor pollicis brevis strength, and thenar
      bulk. CONCLUSIONS: Many patients referred to an electrodiagnostic laboratory with
      a clinical suspicion of CTS have other diagnoses, most commonly musculoskeletal
      disorders. Because these various conditions may be mistaken for CTS, the
      electrodiagnostic evaluation is therefore an important diagnostic tool. Although
      traditional clinical findings including Tinel and Phalen sign were found to have
      limited clinical use, further validation of the groups of positive and negative
      clinical features may potentially enable the referring physician to identify more
      accurately patients who would benefit most from electrodiagnostic testing.

PMID- 11994798
TI  - Evaluation of captopril for the management of hypertension in autonomic
      dysreflexia: a pilot study.
AB  - OBJECTIVE: To evaluate the efficacy of captopril for management of hypertensive
      urgencies in autonomic dysreflexia. DESIGN: A 1-year, prospective, open-label
      pilot study. SETTING: Rehabilitation hospital. PATIENTS: Twenty-six consecutive
      patients older than 15 years with spinal cord injury above T6. INTERVENTIONS:
      During an autonomic dysreflexia episode, captopril 25mg was administered
      sublingually if systolic blood pressure (SBP) was at or above 150mmHg despite the
      use of nondrug measures. If SBP remained elevated 30 minutes after captopril
      administration, 1 dose of immediate-release nifedipine 5mg was given as rescue by
      the bite and swallow method and repeated, if necessary, in 15 minutes. MAIN
      OUTCOME MEASURE: SBP 30 minutes after captopril administration at initial
      autonomic dysreflexia episode. RESULTS: A total of 33 autonomic dysreflexia
      episodes were documented, of which 18 episodes in 5 patients were treated with
      drug therapy. Captopril alone was effective in 4 of 5 initial episodes (80%).
      Mean SBPs at baseline and 30 minutes after captopril were 178+/-18mmHg and 133+/
      28mmHg, respectively. There were no cases of reactive hypotension. The addition
      of nifedipine successfully reduced SBP in the remaining patient. Of the combined
      18 initial and repeat autonomic dysreflexia episodes, 94% were successfully
      treated with our protocol. CONCLUSION: Captopril appears to be safe and effective
      for autonomic dysreflexia management.

PMID- 11994799
TI  - Rehabilitation therapists' recognition of cognitive and mood disorders in
      geriatric patients.
AB  - OBJECTIVE: To determine if physical and occupational therapists can recognize 2
      known predictors of rehabilitation outcome, cognition and mood, in their
      geriatric patients. DESIGN: Survey. SETTING: Urban academic medical center
      rehabilitation unit. PARTICIPANTS: One hundred two consecutive geriatric
      admissions rated by 20 physical and 8 occupational therapists for the presence of
      cognitive or affective disorders. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Mini-Mental State Examination, Geriatric Depression Scale, and
      therapists' ratings. RESULTS: Both disciplines had low rates of accurate
      detection of both cognitive abnormalities and symptoms of depression. Patients
      scoring in the intact range of either domain were more likely to be correctly
      identified by the therapists than were patients whose results were possibly or
      probably impaired. CONCLUSION: Rehabilitation therapists had difficulty
      recognizing patients with cognitive and affective disorders. I recommend
      including a mental health professional on the treatment team, staff inservicing,
      and/or the use of standardized measures of mood and mental status to increase
      recognition of these syndromes in geriatric rehabilitation patients.

PMID- 11994800
TI  - The amputee mobility predictor: an instrument to assess determinants of the lower
      limb amputee's ability to ambulate.
AB  - OBJECTIVES: To describe the development of the Amputee Mobility Predictor (AMP)
      instrument designed to measure ambulatory potential of lower-limb amputees with
      (AMPPRO) and without (AMPnoPRO) the use of a prosthesis, and to test its
      reliability and validity. DESIGN: Measurement study using known groups method and
      concurrence with existing measures. SETTING: Academic medical center.
      PARTICIPANTS: A convenience sample of 191 lower-limb amputee subjects who had
      completed prosthetic training, 24 in the reliability study (mean age +/- standard
      deviation, 68.3+/-17.9y, range, 28-99y) and 167 in the validity study (mean age,
      54.8+/-18.6y; range, 18-100y). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Intra- and interrater reliability; construct validity by known groups
      method; concurrent validity by comparisons with 6-minute walk test, Comorbidity
      Index, age, and time since amputation; predictive validity by comparison with 6
      minute walk test after controlling for other factors. RESULTS: Interrater
      reliability was.99 for subjects tested with and without their prosthesis;
      intrarater reliability was.96 and.97. Both the AMPnoPRO (P<.0001) and the AMPPRO
      scores (P<.0001) distinguished among the 4 Medicare functional classification
      levels. The AMP correlated strongly with 6-minute walk scores (AMPnoPRO r=.69,
      P<.0001; AMPPRO r=.82, P<.0001) and the amputee activity survey (AMPnoPRO r=.67,
      P<.0001; AMPPRO r=.77, P<.0001), and negatively correlated with age (AMPnoPRO r=
      .69, P<.0001; AMPPRO r=.56, P<.0001) and comorbidity (AMPnoPRO r=-.43, P<.0001;
      AMPPRO r=.38, P<.0001). CONCLUSION: The AMP with and without a prosthesis are
      reliable and valid measures for the assessment of functional ambulation in lower
      limb amputee subjects.

PMID- 11994801
TI  - Job satisfaction and health experience of people with a lower-limb amputation in
      comparison with healthy colleagues.
AB  - OBJECTIVES: To describe indicators of job dissatisfaction among amputee employees
      and to compare job satisfaction and health experience of working amputee
      employees with that of control subjects. DESIGN: A cross-sectional study, mailed
      questionnaire. SETTING: Patients were recruited by the orthopedic workshops of
      the Netherlands. PARTICIPANTS: One hundred forty-four patients who had an
      acquired unilateral major amputation of the lower limb at least 2 years before,
      were aged 18 to 60 years (mean age, 43y), and were living and working in the
      Netherlands. One hundred forty-four control subjects matched for age, gender, and
      type of job. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Statistical
      analysis of responses to a questionnaire regarding patient characteristics and
      amputation-related factors, amputee patients' opinions about their work and the
      social atmosphere at work, and their general health (RAND 36-Item Health Survey
      [RAND-36]). RESULTS: People with an amputation had greater job satisfaction (70%)
      than did the able-bodied control group (54%). The wish for (better) modifications
      in the workplace and the presence of comorbidity were significantly related to
      job dissatisfaction in people with limb loss. Amputee employees were less often
      hindered by the failures of others and by fluctuations in temperature. People
      with limb loss showed a worse physical health experience than controls on the
      RAND-36. CONCLUSIONS: The vocational satisfaction of people with limb loss may be
      improved by better workplace modifications, depending on the functional
      capabilities of the person and the functional demands of the job; improvement may
      also be achieved by vocational rehabilitation programs, especially for those with
      an amputation in combination with other morbidity. Despite experiencing more
      health problems, the amputee group expressed greater job satisfaction than the
      able-bodied group, reflecting a great appreciation of job reintegration by people
      with a lower-limb amputation.

PMID- 11994802
TI  - Acute predictors of return to employment after traumatic brain injury: a
      longitudinal follow-up.
AB  - OBJECTIVE: To investigate the relation between selected acute injury and patient
      characteristics and subsequent return to work 1 to 5 years postinjury. DESIGN:
      Longitudinal design with prospectively collected data. Data were collected on
      patients at the time of injury and each year postinjury for up to 5 years.
      SETTING: Four medical centers in the federally sponsored Traumatic Brain Injury
      Model Systems project that provide emergency medical services, intensive and
      acute medical care, inpatient rehabilitation, and a spectrum of community
      rehabilitation services. PARTICIPANTS: Patients were selected from a national
      database of 538 rehabilitation inpatients admitted to acute care within 8 hours
      of traumatic brain injury (TBI) and seen at 1 to 5 years follow-up.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment status (employed
      vs not employed) at 1 to 5 years postinjury. Logistic regression analyses were
      performed to determine the extent to which selected variables predicted
      employment status at years 1 to 5 postinjury. RESULTS: At year 1 postinjury,
      preinjury productivity, age, education, and rehabilitation length of stay were
      all significantly associated with postinjury employment. Preinjury employment and
      productivity and age significantly predicted employment at postinjury year 2. At
      year 3 postinjury, preinjury productivity, age, and FIMtrade mark instrument
      discharge score significantly predicted employment status. Age was significantly
      associated with employment status at year 4 postinjury. Preinjury employment and
      productivity and Disability Rating Scale discharge score were found to be
      significant predictors of postinjury employment at year 5 follow-up. CONCLUSIONS:
      The relationship between certain acute injury and patient variables (eg, age,
      preinjury productivity, education, discharge FIM) and subsequent return to work
      may provide rehabilitation professionals with useful information regarding the
      intensity and types of services needed for individuals in the vocational
      rehabilitation planning process.

PMID- 11994803
TI  - The effect of footrests on sitting balance in paraplegic subjects.
AB  - OBJECTIVE: To test the hypothesis that footrests contribute to active control of
      sitting balance. DESIGN: Cross-sectional group study. SETTING: Rehabilitation
      center. PARTICIPANTS: Ten persons with complete low thoracic (T9-12) spinal cord
      injury (SCI), 10 persons with complete lumbar (L1-5) SCI, and 10 matched able
      bodied controls. INTERVENTION: An elastically suspended footrest. MAIN OUTCOME
      MEASURES: Reaching distance, time needed to perform a bimanual forward-reaching
      movement, center of pressure displacement, and muscle activity. RESULTS: Controls
      performed the forward-reaching movement slower and with less forward acceleration
      of the center of mass (COM) in the chair with the elastic footrest. Furthermore,
      they revealed a typical change in muscle activity patterns when the solid
      footrest was replaced by the elastic one. Persons with SCI performed the forward
      reaching movement equally fast in both footrest conditions, but those with lumbar
      SCI showed less forward acceleration of the COM, whereas persons with thoracic
      SCI revealed more forward acceleration of the COM in the chair with the elastic
      footrest. Muscle activity patterns in persons with SCI did not indicate
      alternative muscle use through possible compensations or reflex activity.
      CONCLUSIONS: Regarding wheelchair design, footrest condition does not seem to
      affect the range in which manual activities of daily living can be performed, but
      it does affect how they are performed.

PMID- 11994804
TI  - Expression of the stress proteins, ubiquitin, heat shock protein 72, and
      myofibrillar protein content after 12 weeks of leg cycling in persons with spinal
      cord injury.
AB  - OBJECTIVE: To determine the effects of leg cycling exercise on ubiquitin (UBI),
      heat shock protein 72 (HSP-72) mRNA, protein expression, and myofibrillar protein
      content in individuals with spinal cord injury (SCI). DESIGN: Case series.
      SETTING: Motor behavior laboratory. PARTICIPANTS: Seven subjects with motor
      complete SCI (4 men, 3 women). INTERVENTION: A 12-week exercise program involving
      an electromagnetically braked recumbent bicycle ergometer, which allowed for
      passive exercise of the legs. Training occurred 2 days a week at approximately
      75% of each subject's maximum heart rate. MAIN OUTCOME MEASURES: Total body mass
      (TBM) and muscle biopsies were obtained pre- and posttraining. The mRNA and
      protein expression of UBI, HSP-72, and myofibrillar protein content were
      determined. RESULTS: Nonsignificant increases (P > .05) of 2.45% were observed
      for TBM. There were significant increases (P < .05) in the expression of both HSP
      72 mRNA (33.71%) and protein (30.23%). For UBI, there were also significant
      decreases (P < .05) in the expression of both mRNA (26.86%) and protein (69.43%).
      Myofibrillar protein content increased significantly (P < .05, 41.86%).
      CONCLUSION: Leg cycling exercise in SCI increases myofibrillar protein content,
      possibly because of up-regulation in the expression of HSP-72 with concomitant
      down-regulation in the expression of UBI.

PMID- 11994805
TI  - Development of an index of physical functional health status in rehabilitation.
AB  - OBJECTIVE: To describe (1) the development of an index of physical functional
      health status (FHS) and (2) its hierarchical structure, unidimensionality,
      reproducibility of item calibrations, and practical application. DESIGN: Rasch
      analysis of existing data sets. SETTING: A total of 715 acute, orthopedic
      outpatient centers and 62 long-term care facilities in 41 states participating
      with Focus On Therapeutic Outcomes, Inc. PATIENTS: A convenience sample of 92,343
      patients (40% male; mean age +/- standard deviation [SD], 48+/-17y; range, 14
      99y) seeking rehabilitation between 1993 and 1999. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Patients completed self-report health status surveys at
      admission and discharge. The Medical Outcomes Study 36-Item Short-Form Health
      Survey's physical functioning scale (PF-10) is the foundation of the physical
      FHS. The Oswestry Low Back Pain Disability Questionnaire, Neck Disability Index,
      Lysholm Knee Questionnaire, items pertinent to patients with upper-extremity
      impairments, and items pertinent to patients with more involved
      neuromusculoskeletal impairments were cocalibrated into the PF-10. RESULTS: The
      final FHS item bank contained 36 items (patient separation, 2.3; root mean square
      measurement error, 5.9; mean square +/- SD infit, 0.9+/-0.5; outfit, 0.9+/-0.9).
      Analyses supported empirical item hierarchy, unidimensionality, reproducibility
      of item calibrations, and content and construct validity of the FHS-36.
      CONCLUSIONS: Results support the reliability and validity of FHS-36 measures in
      the present sample. Analyses show the potential for a dynamic, computer
      controlled, adaptive survey for FHS assessment applicable for group analysis and
      clinical decision making for individual patients.

PMID- 11994806
TI  - A health-related fitness and functional performance test battery for middle-aged
      and older adults: feasibility and health-related content validity.
AB  - OBJECTIVE: To evaluate the feasibility and health-related content validity of 6
      health-related fitness (HRF) and 3 functional performance (FP) tests among middle
      aged and older persons. DESIGN: Cross-sectional methodologic study. SETTING:
      Field laboratories in 3 communities of northeast Finland. PARTICIPANTS: A
      regionally representative, community-based cohort of 55- to 79-year-old men
      (n=501) and women (n=632). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Health-related test exclusion rates (%) by age groups and odds ratios (ORs) of
      subjective health outcomes by fitness categories (least 20%, next 40%, most fit
      40%). RESULTS: The health-related test exclusion rates increased with age, mainly
      because of musculoskeletal health limitations among the women and cardiovascular
      and musculoskeletal health limitations among the men. With the exception of
      dynamic back extension, 1-leg squat, 1-leg standing balance, and the 1-km walk
      among the women 75 years and older, 85% or more of the subjects qualified for the
      HRF tests and 95% or more for the FP tests. Strong and graded associations were
      found for cardiorespiratory and musculoskeletal fitness and the FP test levels
      with perceived health and functional ability status among both the men and the
      women (OR range, 2-31). The motor fitness test level was primarily associated
      with functional ability status. CONCLUSIONS: All the HRF and FP tests showed
      health-related content validity, and 4 of 6 of the HRF tests and all of the FP
      tests proved to be safe, with minor health-related test exclusions for middle
      aged and older adults. The findings may help to target physical activity
      intervention toward persons at high risk for declining health and functional
      ability.

PMID- 11994807
TI  - Functional outcome after inpatient rehabilitation in persons with subarachnoid
      hemorrhage.
AB  - OBJECTIVES: To describe inpatient rehabilitation outcome in persons with
      nontraumatic subarachnoid hemorrhage (SAH) and to explore the predictive capacity
      of acute measures of SAH severity and demographic and disease variables. DESIGN:
      Retrospective with descriptive and relational analyses. SETTING: Free-standing,
      acute, inpatient brain injury rehabilitation unit. PARTICIPANTS: Forty-two
      consecutive persons with nontraumatic SAH and for whom complete data were
      available were studied. Mean age of the group was 56.5 years, mean acute hospital
      stay was 26.2 days, and 60% were women. Over 40% experienced rupture of an
      anterior communicating artery aneurysm. The time from injury to rehabilitation
      admission varied from 11 to 227 days (mean, 43.8d). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: Change in FIMtrade mark instrument scores, home
      discharge rate, and rehabilitation length of stay (LOS.) RESULTS: The mean
      admission and discharge FIM scores were 57.7 and 85.5 points, respectively. There
      was a 27.8-point mean change in FIM score over a 24.1-day mean rehabilitation LOS
      for a FIM efficiency (points/day) of 1.15. Over 80% of the sample was discharged
      home. No demographic or disease characteristic variables, including acute
      severity measures, were statistically significant predictors of outcome.
      CONCLUSIONS: Functional gains during inpatient rehabilitation made in this group
      of 42 persons with SAH are in line with earlier studies. Our rehabilitation LOS
      is the shortest reported among 4 studies to date and is probably a reflection of
      managed care in the United States. A small sample, uneven cell sizes, and
      variability of patients might have contributed to a lack of significant findings.
      Future study should explore the prediction of rehabilitation outcome using larger
      sample sizes and longer follow-up periods.

PMID- 11994808
TI  - Step training with body weight support: effect of treadmill speed and practice
      paradigms on poststroke locomotor recovery.
AB  - OBJECTIVE: To investigate the effect of practice paradigms that varied treadmill
      speed during step training with body weight support in subjects with chronic
      hemiparesis after stroke. DESIGN: Randomized, repeated-measures pilot study with
      1- and 3-month follow-ups. SETTING: Outpatient locomotor laboratory.
      PARTICIPANTS: Twenty-four individuals with hemiparetic gait deficits whose
      walking speeds were at least 50% below normal. INTERVENTION: Participants were
      stratified by locomotor severity based on initial walking velocity and randomly
      assigned to treadmill training at slow (0.5mph), fast (2.0mph), or variable (0.5,
      1.0, 1.5, 2.0mph) speeds. Participants received 20 minutes of training per
      session for 12 sessions over 4 weeks. MAIN OUTCOME MEASURE: Self-selected
      overground walking velocity (SSV) was assessed at the onset, middle, and end of
      training, and 1 and 3 months later. RESULTS: SSV improved in all groups compared
      with baseline (P<.001). All groups increased SSV in the 1-month follow-up (P<.01)
      and maintained these gains at the 3-month follow-up (P=.77). The greatest
      improvement in SSV across training occurred with fast training speeds compared
      with the slow and variable groups combined (P=.04). Effect size (ES) was large
      between fast compared with slow (ES=.75) and variable groups (ES=.73).
      CONCLUSIONS: Training at speeds comparable with normal walking velocity was more
      effective in improving SSV than training at speeds at or below the patient's
      typical overground walking velocity.

PMID- 11994809
TI  - Effectiveness of femoral nerve selective block in patients with spasticity:
      preliminary results.
AB  - OBJECTIVES: To determine if the vastus intermedius nerve can be blocked by using
      surface coordinates and to measure the effects of selective nerve block on
      quadriceps spasticity and immediate gait. DESIGN: Case series. SETTING: Physical
      medicine and rehabilitation department of a university hospital. PARTICIPANTS:
      Twelve patients with hemiplegia disabled by quadriceps overactivity.
      INTERVENTION: Anesthesic block of the vastus intermedius by using surface
      coordinates, femoral nerve stimulation before and after block, and surface
      electrodes recording of the amplitude of the maximum direct motor response of
      each head of the quadriceps. MAIN OUTCOME MEASURES: Assessment of spasticity,
      voluntary knee extension velocity, speed of gait, and knee flexion when walking.
      RESULTS: To be effective, the puncture point (.29 of thigh length and 2cm
      lateral) had to be slightly modified to 1cm laterally from a point situated at
      0.2 of the thigh length. A selective block of the vastus intermedius could not be
      achieved, but a block of the vastus lateralis was always achieved, twice
      associated with a block of the vastus intermedius, resulting in decreased
      quadriceps spasticity, no changes in gait parameters, no decrease in voluntary
      knee extension velocity, and subjective improvement in gait for 3 patients.
      CONCLUSION: Selective block of the vastus lateralis with or without the vastus
      intermedius can be achieved by using surface coordinates without any dramatic
      effect on knee extension velocity, and it could be useful for phenol or alcohol
      block or surgical neurotomy.

PMID- 11994810
TI  - Radiation exposure of the spinal interventionalist performing fluoroscopically
      guided lumbar transforaminal epidural steroid injections.
AB  - OBJECTIVE: To evaluate radiation exposure to spinal interventionalists while
      performing transforaminal epidural steroid injections (TFESIs). DESIGN:
      Prospective study. SETTING: Multidisciplinary spine center. PARTICIPANTS: One
      hundred consecutive patients with either herniated nucleus pulposus (HNP) or
      lumbar spinal stenosis (LSS). INTERVENTION: Fluroscopically guided lumbar TFESIs.
      MAIN OUTCOME MEASURE: Radiation exposure was monitored by radiography
      technologists who allocated 4 dosimetry badges to all spinal interventionalists
      performing fluroscopically guided lumbar TFESIs on patients being treated for
      radicular pain. Badges were placed on the ring finger, glasses, and the inside
      and outside of the lead apron worn by the interventionalists. The radiography
      technologists also wore marked badges outside their lead aprons. One control
      badge was placed 67in away from the fluoroscopy table and a second badge was
      placed in a desk more than 500ft away from the procedure to monitor ambient
      radiation. RESULTS: The average fluoroscopy time per procedure was 15.16 seconds.
      The average exposure per procedure was 0.7mrem at the ring badge, 0.4mrem at the
      glasses badge, and 0.3mrem at the outside apron badge. No radiation was
      detectable at the inside apron or at the outside room control badge. The
      cumulative exposure to the interventionalists from all 100 procedures was 70mrem
      at the ring badge, 40mrem at the glasses badge, and 30mrem at the outside apron
      badge. The radiography technologists' average exposure during these procedures
      was below the limit of detectablility. Radiation time under fluoroscopy ranged
      from 5 to 38 seconds. The interventionalist's exposure to radiation was
      significantly greater during procedures conducted on patients with LSS then
      during procedures on patients with HNP. CONCLUSION: Adhering to a radiation
      safety program that includes maximizing the distance the spinal interventionalist
      is from the radiation source, decreasing exposure time, and proper shielding is
      essential when performing fluoroscopically guided lumbar TFESIs. Our study shows
      that exposure to radiation of the spinal interventionalist performing
      fluoroscopically guided lumbar TFESIs was well within safety limits when proper
      techniques were followed.

PMID- 11994811
TI  - Alterations in reaching after stroke and their relation to movement direction and
      impairment severity.
AB  - OBJECTIVES: To examine the effects of stroke severity and target location on
      reaching (1) to identify regions in space that are difficult to reach, (2) to
      determine whether specific alterations in reaching are associated with particular
      clinical impairment levels, and (3) to characterize relationships between
      reaching alterations. DESIGN: Participants reached toward a screen of 75 targets
      spanning an approximate range from +/-90 degrees side to side and from waist to
      head. SETTING: Rehabilitation research center. PARTICIPANTS: Sixteen chronic
      stroke patients with a wide range in residual arm function and 4 control
      subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Chedoke-McMaster
      Stroke Arm Assessment, distance, velocity, smoothness, straightness, and
      direction of the hand path during each reach. Hand position trajectories were
      recorded with an electromagnetic sensor. RESULTS: Reaches performed with the
      impaired arms showed significant degradation in all performance measures.
      Although only modestly dependent on the target location, these features
      correlated strongly with impairment level, as well as with each other. Reaching
      distance showed the strongest correlations with the other parameters.
      CONCLUSIONS: Stroke alters a broad array of features of reaching, yet largely the
      same degree of movement control is preserved across a range of target locations.
      The only consistently problematic task is to reach far out from the torso,
      independent of the movement direction. Thus, active range of motion (AROM),
      rather than control over a specific subset of movement directions, is a logical
      focus for therapy. In addition, measuring AROM is a simple clinical measure that
      yields much information.

PMID- 11994812
TI  - A comparison of the effects of exercise and lifestyle modification on the
      resolution of overuse symptoms of the shoulder in polio survivors: a preliminary
      study.
AB  - OBJECTIVE: To compare the effectiveness of exercise and lifestyle modification
      therapy in treating shoulder symptoms in polio survivors with lower-extremity
      weakness. DESIGN: A randomized parallel group study. SETTING: Research
      laboratory. PARTICIPANTS: Twenty-three subjects recruited from a cohort of 194
      polio survivors who had participated in a previous study had bilateral hip
      extensor and knee-extensor weakness and reported experiencing shoulder pain on a
      regular basis with daily activity. INTERVENTIONS: Subjects were randomly assigned
      to 1 of 3 treatment groups. Members of group 1 were placed on a home exercise
      program that focused on strengthening their hip and knee extensors. Members of
      group 2 were instructed in lifestyle modification techniques designed to avoid
      shoulder overuse. Members of group 3 received both interventions. MAIN OUTCOME
      MEASURES: Shoulder symptoms were quantified in terms of number and severity.
      Isometric strength of bilateral hip and knee extensors was measured with a hand
      held dynamometer. RESULTS: Symptoms improved in all 3 groups. However, members of
      the exercise-only group (group 1) were the only ones to show a significant
      difference in both number and severity of symptoms when pre- and posttreatment
      values were compared. CONCLUSIONS: Both exercise and lifestyle modification
      therapies that focus on reducing the stress related to lower-extremity weakness
      are effective in treating shoulder overuse symptoms in polio survivors. A trend
      toward greater improvement in shoulder symptoms in subjects who participated in
      the exercise program and who also showed a trend toward increased knee-extensor
      strength supports muscle strength and/or endurance as a key factor.

PMID- 11994813
TI  - Treatment of detrusor-sphincter dyssynergia by pudendal nerve block in patients
      with spinal cord injury.
AB  - OBJECTIVE: To study the effects of pudendal nerve block with phenol on detrusor
      sphincter dyssynergia in patients with spinal cord injury (SCI). DESIGN: Before
      after trial performed by using a consecutive sample. SETTING: Rehabilitation
      hospital affiliated with a medical school. PATIENTS: Twenty-two male SCI patients
      (mean age, 46.3+/-11.9y; mean duration postinjury, 2.7y) with voiding dysfunction
      resulting from external urethral sphincter hypertonicity. INTERVENTION: Pudendal
      nerve block with 5% phenol solution under the guidance of electric stimulator.
      MAIN OUTCOME MEASURES: Outcomes were measured using (1) postvoid residual volume,
      maximal detrusor pressure, leak point pressure, bladder volume at the first
      uninhibited contraction, maximal bladder capacity, and urethral pressure profile;
      (2) rectoanal rest and squeeze pressures; and (3) quality of life measures for
      urination, quantified by the Quality of Life Index (QLI). Changes in bowel habit
      or autonomic dysreflexia were recorded. RESULTS: The mean decrease in postvoid
      residual volume was 242.8mL (mean decrease, 66%) after treatment (P<.001). The
      mean reduction in leak point pressure and maximal detrusor pressure were
      37.1cmH(2)O and 43.3cmH(2)O, respectively (P<.05). The mean QLI significantly
      improved from -.74+/-.38 to.42+/-.47 (P<.001). The rectoanal pressures showed no
      significant difference. No complaints of fecal incontinence or other
      complications were noted after treatment. CONCLUSION: Pudendal nerve block
      performed by using 5% phenol solution was safe, easy to perform, and effective as
      a treatment for detrusor-sphincter dyssynergia in selected patients with SCI.

PMID- 11994814
TI  - Propulsion patterns and pushrim biomechanics in manual wheelchair propulsion.
AB  - OBJECTIVES: To classify stroke patterns of manual wheelchair users and to
      determine if different patterns of propulsion lead to different biomechanics.
      DESIGN: Case series. SETTING: Biomechanics laboratory. PARTICIPANTS: Thirty-eight
      individuals with paraplegia who use manual wheelchairs for mobility.
      INTERVENTION: Subjects propelled their own wheelchair on a dynamometer at 2
      different steady state speeds. Bilateral biomechanical data were obtained by
      using a force and moment sensing pushrim and a motion analysis system. MAIN
      OUTCOME MEASURES: The propulsive stroke of each participant for each speed and
      side was classified as following 1 of 4 patterns. These 4 patterns were then
      compared by using a mixed-model analysis of variance. The biomechanical variables
      that were compared were cadence, peak and rate of rise of the resultant force,
      mechanical effective force, push angle, and ratio of time spent pushing to time
      in recovery. RESULTS: The most common propulsive stroke involved the user lifting
      the hand over the pushrim during the recovery phase. The stroke pattern was
      independent of axle position and varied from side to side and between speeds.
      After controlling for subject characteristics, significant differences were
      observed between stroke patterns in cadence and ratio of time spent pushing to
      time in recovery. A stroke pattern that involves using a semicircular motion with
      the hand below the pushrim during the recovery phase of the propulsion stroke was
      associated with a lower cadence and more time spent in the push phase relative to
      the recovery phase. CONCLUSION: The semicircular motion of propulsion displayed
      characteristics consistent with reduced repetition and more efficient propulsion.
      Use of this propulsion style may reduce trauma to the upper extremities.
      Clinicians should consider training individuals in this propulsion style.

PMID- 11994815
TI  - Importance of physical rehabilitation before and after cardiac transplantation in
      a patient with myotonic dystrophy: a case report.
AB  - Patients with muscular dystrophy and concomitant cardiomyopathy are only
      reluctantly accepted for heart transplantation because of the perioperative risk
      secondary to respiratory muscle weakness. We describe a man with Steinert's
      disease (myotonic dystrophy) who received a cardiac allograft because of end
      stage dilated cardiomyopathy. This case shows the importance of uninterrupted
      physiotherapeutic training and assistance to minimize respiratory infections and
      ventilatory insufficiency in patients with muscle diseases under high-dose
      immunosuppression. To our knowledge, this is the first heart transplantation
      reported in a patient with Steinert's disease who has clinically overt muscular
      impairment.

PMID- 11994816
TI  - An unusual case of electromyographic recorded myokymic potentials: a case report.
AB  - Abnormal spontaneous potentials, specifically myokymia, can occur from various
      causes. We present the case of a 64-year-old woman with a 12-month history of
      left leg weakness and difficulty descending stairs. The patients' medical history
      was significant for breast carcinoma (no node involvement), hypercholesterolemia,
      and vitamin B(12) deficiency. She previously had a modified radical mastectomy
      and received chemotherapy (5-flurouracil, methotrexate, Cytoxan
      [cyclophosphamide]), but received no radiation. She took simvastatin for
      hypercholesterolemia and received vitamin B(12) injections for her B(12)
      deficiency. She initially noticed her symptoms when she began taking simvastatin,
      and they were exacerbated when her dose was increased from 10 to 20mg/d.
      Electrodiagnostic studies were performed twice at a 6-month interval. Nerve
      conduction studies were normal, but the initial needle electromyography showed
      significant myokymic discharges in bilateral iliopsoas, adductor magnus, and left
      deltoid muscles. The second electromyograph had similar findings, except for the
      absence of myokymic discharges in the left deltoid muscle. The possible origins
      of these myokymic discharges are discussed.

PMID- 11994817
TI  - Usefulness of transcranial magnetic stimulation to predict the development of
      reflex sympathetic dystrophy poststroke: a pilot study.
AB  - OBJECTIVE: To investigate the predictive value of transcranial magnetic
      stimulation (TMS) for the development of reflex sympathetic dystrophy (RSD)
      poststroke. DESIGN: Blind clinical assessment of 2 groups of stroke patients
      defined on the basis of absent or preserved motor evoked potentials (MEPs) on the
      affected side. SETTING: Stroke rehabilitation center. PATIENTS: Twenty stroke
      patients between the ages of 41 and 85 years, undergoing rehabilitation.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: MEPs from upper limbs 30
      days poststroke, Motricity Index, and scoring of RSD using the Enjalbert Scale 73
      days poststroke. RESULTS: A good correlation was found between Motricity Index
      and TMS results (P<.01). Average Enjalbert scores were significantly different
      between the 2 groups (P=.03). No significant correlation was found between
      Enjalbert scores and the Motricity Index. CONCLUSIONS: Although no significant
      relationship was found between upper-limb motor impairment and intensity of RSD
      10 weeks after stroke, the TMS responses permitted the early categorization of
      patients into 2 groups that developed significantly different average Enjalbert
      scores 1 to 2 months later when this clinical condition was fully developed.

PMID- 11994818
TI  - Ipsilateral, but via the callosum: a technical definition of handedness.

PMID- 11994820
TI  - Multidisciplinary and interdisciplinary research: what it is and what it is not.

PMID- 11994821
TI  - Nurse practitioner and physician communication styles.
AB  - No empirical studies of nurse-patient relationships have focused on interpersonal
      communication and its effects on patient outcomes. In this study, 124 provider
      patient interactions of five nurse practitioners (NPs) and four physicians (PHYs)
      were audiotaped. Communication patterns were examined to determine whether the
      practitioner's predominant style was informational or controlling and whether
      style affected patient satisfaction and perceived autonomy support. All providers
      used predominantly informational styles of communication. Significant differences
      in communication styles existed between provider groups (F = 5.90, df = 1/8, p
      =.05) and among individual providers (F = 4.28, df = 8/123, p <.0001). All
      providers were more controlling in their communication patterns when attempting
      to make decisions and plan patient care. Examination of communication styles can
      help NPs develop the skills necessary to provide patient-centered care.

PMID- 11994822
TI  - Environmental health and nursing practice: a survey of registered nurses.
AB  - The purpose of this study was to develop and implement a survey for Registered
      Nurses (RNs) that explored beliefs regarding environmental health (EH) and
      nursing practice, perceived preparation related to EH, barriers to addressing EH
      in practice, and factors that may facilitate integrating EH into nursing
      practice. Five hundred surveys were mailed, with a 39% return rate. Results
      indicate that RNs believe the environment and human health are related, but feel
      poorly prepared to address EH in practice. Barriers and facilitators to
      integrating EH into practice were found. The need for programs and resources to
      ensure basic EH education for all nurses was substantiated.

PMID- 11994823
TI  - Measuring health-related quality of life in children with heart disease.
AB  - This study tested an instrument for measuring health-related quality of life
      (HRQL) in children with heart disease. HRQL was measured using the New York
      University Children's Heart Health Survey in a sample of 0- to 20-year-old
      subjects with heart disease compared with a control group. Heart disease was
      associated with impairment on all subscales except psychological function.
      Adolescent self-reports did not differ significantly between the cardiac group
      and healthy controls in any of the subscales. This instrument may be useful in
      assessing the impact of various treatment strategies in this population.

PMID- 11994824
TI  - The duration and degree of end-of-life dependency of home care clients and
      hospital inpatients.
AB  - This investigation sought to describe and compare dependency among dying persons.
      To accomplish this, healthcare records of all deceased persons who received care
      over a 6-month period in one Canadian hospital (n = 150) and one home care
      department (n = 59) were reviewed. Only 36% of the home care clients died at
      home; all others (n = 38) were hospitalized. Almost all subjects had dependency
      needs on admission to care, with dependency increasing until all were completely
      dependent near death. Hospitalized home care clients had the longest documented
      average duration of total (partial and complete) dependency (81.3 days). Types of
      dependency (partial and complete) and progression in dependency were similar
      among subject groups, with the exception of 26% of hospital inpatients, who
      suddenly developed complete dependency until death. The duration of complete
      dependency varied between and among subject groups, which explains why a
      significant difference in lengths of complete dependency between hospital
      inpatients (M = 8.3 days) and home care clients who died at home (M = 4.1 days)
      was not found. In light of a dearth of research-based knowledge, this information
      should facilitate an improved understanding of the dependency needs of dying
      persons. Ultimately, it should assist end-of-life care planning and policy
      making.

PMID- 11994825
TI  - Theory-based intervention for dementia behaviors: a within-person analysis over
      time.
AB  - The historic "black-box" approach to treatment effectiveness research has
      hampered the development of effective activity interventions for persons with
      dementia. The purpose of this case study is to test the effectiveness of
      activities derived from the Need-Driven Dementia-Compromised Behavior Model.
      Activities that matched skill level and personality style of interest resulted in
      a pattern of greater time on task (p =.0012), participation (p =.004), and
      positive mood (p =.0001) and fewer dementia-related behaviors (p =.009) compared
      with activities matched to skill level only. Practitioners may improve behavioral
      outcomes for persons with dementia by prescribing activities based on an
      assessment of skill level and style of interest.

PMID- 11994826
TI  - An HIV risk-reduction intervention in an adolescent correctional facility:
      lessons learned.
AB  - Adolescents are now being described as the generation most at risk for human
      immunodeficiency virus (HIV) infection. Incarcerated young women remain a group
      at even greater risk, with markedly higher HIV seroprevalence rates compared with
      their male counterparts. In preparing for a longitudinal, randomized, controlled
      trial, our research team conducted a pilot project with incarcerated adolescent
      women. The purpose of this report is to offer clinicians and researchers
      interested in working with this population some insights on how to approach young
      women in detention and the logistics of carrying out a program in a correctional
      facility.

PMID- 11994827
TI  - Transdermal fentanyl for the management of acute pancreatitis pain.
AB  - Although the hazards of using Demerol for pain management is well documented,
      physicians at a 350-bed tertiary-care center in the upper midwest continued to
      follow the antiquated practice of ordering intramuscular Demerol and Vistaril to
      manage pain for patients with acute pancreatitis. Their reasoning was based on
      early evidence that Demerol, unlike morphine, does not cause biliary-tract spasms
      resulting in epigastric or right upper quadrant pain. In an effort to change
      practice patterns, a multidisciplinary team was formed to study the efficacy of
      using Transdermal Therapeutic System (TTS) fentanyl to manage pain in this
      patient population. Thirty-two subjects were enrolled in a double-blind, placebo
      controlled study to evaluate the efficacy of using TTS fentanyl with
      intramuscular Demerol for breakthrough pain in comparison to using a placebo
      system and intramuscular Demerol. There was no statistically significant
      difference in self-reported pain intensity between the control and experimental
      groups on the first day of hospitalization. This finding would be expected
      because serum fentanyl concentrations rise gradually during the first 12 to 14
      hours after application of the TTS fentanyl and plateau at 24 hours. There was a
      statistically significant difference between groups at 36 hours (exact p <.0154)
      and 45 hours (exact p <.0132) after application of the TTS fentanyl. This is
      probably because of greater serum fentanyl concentrations observed during the 36-
      to 48-hour period after application of TTS fentanyl. Although not statistically
      significant, trends in the data revealed that the experimental group had lower
      self-reported pain intensity scores than the control group throughout the course
      of hospitalization. Even though the experimental group had significantly more
      previous hospitalizations for acute pancreatitis and a higher pain intensity
      score on admission, this group had a significantly shorter length of stay in the
      hospital c2 (1, N = 31) = 4.3706 p <.05. There was no statistically significant
      difference between the two groups for self-reported satisfaction with pain
      management.

PMID- 11994828
TI  - Nursing and health care in socialist Cuba: what can we learn from each other?

PMID- 11994831
TI  - Nursing shortage and nursing sensitive outcomes.

PMID- 11994832
TI  - Are we witnessing the disappearance of catatonic schizophrenia?
AB  - The decrease in the frequency of diagnosed catatonic subtypes among schizophrenic
      disorders as a whole during the last 50 years has long been regarded as an
      established fact. Until now the factors responsible for this development have
      been under discussion. As it is not clear if there is a true decrease or an
      ostensible one due to other factors such as changed diagnostic habits or
      neuroleptic treatment, we examined 174 consecutively admitted schizophrenic
      patients from three different psychiatric institutions diagnosed according to DSM
      IV and Leonhard's criteria. It turned out that-depending on the diagnostic system
      the rates of diagnosed catatonias were 10.3% (DSM-IV) and 25.3% (Leonhard's
      criteria). Comparison of the two original Leonhard cohorts (1938 to 1968, 1969 to
      1986) with our own (1994 to 1999) shows a decrease in the frequency of catatonias
      from 35% to 25%, which-albeit statistically significant-is much less pronounced
      than in studies that used a narrower definition of catatonia. Here, besides
      sociocultural developments, the use of neuroleptics seems to effect the decrease
      in the frequency of catatonias in two ways: on one hand, they cause a decrease of
      hyperkinesia, excitement, or impulsivity; while on the other hand, they
      themselves produce motor abnormalities like rigidity, effects that favor the
      attribution of motoric symptoms to neuroleptics.

PMID- 11994833
TI  - Sensory acuity and reasoning in delusional disorder.
AB  - Systematic research on delusional disorder (DD) is limited. The goal of this
      study was to assess DD patients in the following areas: sensory capacities,
      decision-making style, and complex reasoning. Ten DD patients and 10 matched
      normal controls completed the following (1) smell, taste, and vision testing; (2)
      a probabilistic inference test in which subjects made probability decisions; and
      (3) a gambling task assessing complex reasoning. No significant difference was
      found between DD subjects and normals for taste acuity, olfactory acuity, or
      olfactory discrimination. No difference in visual acuity was noted, but sample
      size was limited. In addition, DD subjects required significantly less data to
      make probability decisions than normal controls. Despite using less data, DD
      subjects were as certain as controls regarding the accuracy of their decisions.
      As for complex reasoning, DD subjects performed as well as normal controls, but
      tended to surmise the purpose of the task sooner than normals, a difference that
      approached significance. In conclusion, these results suggest no differences
      between DD and normal subjects regarding olfaction, taste, and vision. The
      reasoning studies suggest that DD subjects may have a "cognitive set" that
      predisposes them to make conclusions with significantly less data than normals.
      Further, the study suggests that this reasoning difference generalizes to events
      outside the DD subjects' delusional realm and can be evoked in an experimental
      environment.

PMID- 11994834
TI  - Symptom profile consistency in recurrent manic episodes.
AB  - Few studies have addressed whether symptom profiles remain consistent between
      episodes of mania. Those that have done so focused on mood only and adopted the
      strictly categorical approach. We evaluated 77 subjects during two discrete manic
      episodes (mean interval, 2 years, 2 weeks). Episodes were characterized on five
      established symptom factors of mania and on overall severity of classic manic
      symptoms (i.e., excluding dysphoric symptoms). Pearson correlation coefficients
      were computed to compare symptom profiles across episodes. Four symptom factors
      (dysphoria, hedonic activation, psychosis, and irritable aggression) were
      significantly correlated across episodes, as was manic severity. Psychomotor
      symptoms were not significantly correlated. Manic symptomatology remains
      generally similar in bipolar subjects during different episodes. The
      characterization of manic episodes by the empirical dimensions of symptom
      factors, as suggested by Kraepelin nearly a century ago, may provide additional
      information for biological and treatment response studies of manic states that is
      not captured by categorical subtype diagnosis focused solely on mood symptoms
      (i.e., mixed v pure manic episodes).

PMID- 11994835
TI  - The effect of cognitive-behavioral therapy for bulimia nervosa on temperament and
      character as measured by the temperament and character inventory.
AB  - Cognitive-behavioral therapy (CBT) is a successful treatment method for reducing
      symptomatology associated with bulimia nervosa (BN). Less is known regarding the
      impact of CBT on measures of temperament and character across treatment. We
      explore changes on the Temperament and Character Inventory (TCI) from
      pretreatment to 1-year follow-up in a sample of women with bulimia nervosa (BN).
      Ninety-one women who met DSM-III-R criteria for BN, completed pretreatment
      measures, and participated in a randomized clinical trial with a core treatment
      of CBT were available for follow-up at 1 year. Participants were assessed at
      pretreatment using the TCI as part of a larger assessment battery, and received
      eight sessions of CBT and eight sessions of exposure with response prevention or
      relaxation training. The TCI was readministered at the 1-year follow-up point. We
      compared TCI scores across the two administrations and explored the relation
      between clinical status at 1 year and TCI scores. Significant decreases in the
      TCI temperament scale of harm avoidance and increases in the character scale of
      self-directedness were observed between pretreatment and 1-year follow-up.
      Observed differences in these scales were independent of change in depression
      scores as well as other measures of therapeutic change (i.e., binge and purge
      frequency). We conclude that self-directedness and harm avoidance scores are
      positively affected by CBT. Higher scores on self-directedness not only predict
      treatment outcome for BN, but overall self-directedness is improved with CBT in
      women with BN. These results suggest that the elements of CBT affecting self
      directedness may hold promise for enhancing the effectiveness of treatment for
      BN.

PMID- 11994836
TI  - Sensitivity to the rewarding effects of food and exercise in the eating
      disorders.
AB  - The diminished capacity to experience pleasure or reward ("anhedonia") has its
      biological underpinnings in the mesolimbic dopamine system and is strongly
      implicated in risk for a variety of addictive behaviors. The present study tested
      the prediction that patients with anorexia nervosa (AN) would be more anhedonic
      than those with bulimia nervosa (BN)-a factor that could contribute to their
      respective avoidance and approach relationship to food. We also tested the idea
      that anhedonia would be correlated with high-level exercising from the viewpoint
      that the latter serves as a compensatory behavior for a blunted affect. AN
      patients of the restrictor subtype (n = 78) and BN patients with no history of AN
      (n = 76) were included in the regression analyses. Patients were also classified
      as excessive exercisers or moderate/nonexercisers according to information
      gathered during a structured clinical interview. Findings were largely supportive
      of our predictions. AN patients were highly anhedonic compared to BN patients,
      and excessive exercisers tended to be more anhedonic than those who did not
      exercise. We discuss the AN-BN differences in capacity for reward/pleasure in the
      context of the common psychobiological links between the eating disorders and
      drug and alcohol addiction, and speculate on how these differences might relate
      to the etiology and pathophysiology of both AN and BN.

PMID- 11994837
TI  - Trauma and dissociation in treatment-seeking alcoholics: towards a resolution of
      inconsistent findings.
AB  - There is consistent empirical evidence for a trauma-dissociation relation in
      general population samples and in psychiatric patients. However, contradictory
      findings have been reported on this relation among substance abusers. The present
      study attempts to resolve these inconsistencies by testing a series of hypotheses
      related to problems regarding the measurement of childhood abuse, the measurement
      of psychological dissociation, and the potential existence of substance abuse as
      a form of chemical dissociation. Alcoholic patients (N = 155) were administered
      the Dissociative Experiences Scale (DES), the Structured Trauma Interview (STI),
      the European Addiction Severity Index (EuropASI), and the Posttraumatic Stress
      Disorder (PTSD) section of the Composite International Diagnostic Interview
      (CIDI). The DES showed good psychometric properties. Substantial rates of
      traumatization and PTSD were observed, as well as a significant trauma-PTSD
      relation. However, the mean DES score was low (11.4) and dissociation was not
      related to trauma (childhood or lifetime) or to PTSD. Years of lifetime regular
      medicine use, however, was significantly correlated with the severity of
      dissociative symptoms and PTSD, particularly in males. Overall, these findings
      suggest that absence of a trauma-dissociation relation in alcoholics may not be
      due to measurement problems of childhood abuse and/or dissociation. Rather, a
      trauma-dissociation link may not exist, particularly in male alcoholics, because
      these individuals may abuse substances to achieve dissociative-like states.
      Additional research is needed to further evaluate the utility of the DES in
      alcoholic samples and to examine the notion of chemical dissociation.

PMID- 11994838
TI  - Comorbid conditions in obsessive-compulsive disorder.
AB  - The objective of this study was to investigate axis I comorbidity in obsessive
      compulsive disorder (OCD). A total of 147 patients diagnosed as OCD for DSM-III-R
      criteria were included in the study. At least one comorbid axis I disorder was
      present in 68.7% of the patients. Major depression was the most common comorbid
      disorder (39.5%). Uncomplicated (n = 46) and comorbid (n = 101) OCD groups were
      compared with respect to the demographic variables and the scores obtained from
      the Hamilton Rating Scale for Anxiety (HRSA), the Hamilton Rating Scale for
      Depression (HRSD) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). No
      significant difference in terms of age, sex, marital status, age at onset, or
      duration of illness was found between the groups. The scores on the HRSA, HRSD,
      and Y-BOCS were significantly higher in the comorbidity group. Our results
      demonstrate that at least one psychiatric disorder is present in approximately
      two thirds of OCD patients, the majority being depressive disorders and anxiety
      disorders. The fact that comorbid conditions raise not only anxiety and
      depression levels, but also the severity of obsessions and compulsions, is
      noteworthy.

PMID- 11994839
TI  - Interrelations between temperament, character, and parental rearing among
      delinquent adolescents: a cross-validation.
AB  - We performed a cross-validation of results from investigations in juvenile
      delinquents in Russia and Germany concerning relationships of personality
      characteristics in terms of temperament and character with parental rearing. Both
      studies used the Temperament and Character Inventory (TCI) based on Cloninger's
      psychobiological theory, and the Own Memories on Parenting (Egna Minnen
      Betraffande Uppfostran-Swedish [EMBU]) questionnaire on parental rearing based on
      Perris' vulnerability model. The inter-relatedness of parental rearing,
      temperament, and character traits in socially normally integrated adolescents, as
      well as in delinquent adolescents, implying direct and indirect pathways from
      personality and parental rearing to delinquency, could be cross-validated.
      Differences between delinquents and socially normally integrated adolescents are
      rather based on different levels of expressions of various temperament traits,
      harm avoidance and novelty seeking in particular, and the character trait self
      directedness, as well as on parental rearing behavior (predominantly parental
      rejection and emotional warmth) than on different structures within related
      developmental processes.

PMID- 11994840
TI  - Self-harm behaviors across the life cycle: a pilot study of inpatients with
      borderline personality disorder.
AB  - The purpose of this study was to explore, throughout the life cycle, the
      prevalence of self-harm behaviors among psychiatric inpatients with and without
      borderline personality disorder (BPD). Psychiatric inpatients with BPD (n = 43)
      were compared to those without BPD (n = 40) with regard to self-reported self
      harm behaviors during their lifetime. The mean number of self-harm behaviors,
      including high-lethal behaviors (i.e., suicide attempts, cutting oneself,
      overdosing), among those with BPD dramatically increased between the ages of 18
      and 24 years and was sustained through ages 50 to 59 years. Non-BPD patients
      showed a similar pattern, but the means were notably less. These data suggest
      that the behavioral "burn out" theory of personality disorders does not
      necessarily occur among inpatients with BPD.

PMID- 11994841
TI  - Burden on family members of the mentally ill: a naturalistic study in Japan.
AB  - People with mental disorders often cause distress among their family members. We
      examined a total of 25 pairs of newly referred psychiatric patients and their
      family members to investigate the correlations between family burden and patient
      diagnosis (using the Structured Clinical Interview for DSM-III-R [SCID] axis I
      disorders), symptomatic severity (Positive and Negative Symptoms Scales [PANSS]),
      global function (Global Assessment of Functioning [GAF]), and the general level
      of family function (Family Adaptability and Cohesion Evaluation Scale [FACES]).
      The subjective and objective burdens on the family were assessed by self-report.
      The subjective and objective burdens were significantly predicted only by the GAF
      score.

PMID- 11994842
TI  - Temperament and early environmental influences in kleptomania.
AB  - The purpose of this investigation was to shed light on the temperament and early
      life experiences of people suffering from kleptomania. Twelve outpatients (five
      men [41.6%]; seven women [58.3%]; mean age, 39.6 +/- 11.0 years) who met DSM-IV
      criteria for kleptomania and had no other axis I disorders by Structured Clinical
      Interview for DSM-IV (SCID) completed the Tridimensional Personality
      Questionnaire (TPQ) and the Parental Bonding Instrument (PBI). Patients with
      kleptomania had significantly higher novelty-seeking scores (P =.001), higher
      harm-avoidance scores (P =.005), and lower reward-dependence scores (P =.023)
      than normal controls. The kleptomania subjects had significantly lower maternal
      and paternal care scores, and lower maternal protection scores, than the
      normative values (P <.05). Neither TPQ nor PBI scores correlated with illness
      severity. These findings suggest that an understanding of early parenting
      behavior and a dimensional approach to the personality of kleptomaniacs may offer
      insight into this disorder and provide clues to treatment strategies.

PMID- 11994843
TI  - Assessing psychological distress in psychiatric patients: validation of the
      Talbieh Brief Distress Inventory.
AB  - The present study examined the psychometric properties of the Talbieh Brief
      Distress Inventory (TBDI), a 24-item self-report instrument used to measure
      psychological distress, for use in psychiatric patients. A case-control and
      partly longitudinal design was used to test the TBDI among 431 psychiatric
      outpatients and inpatients and 197 gender- and age-matched nonpatients. All
      respondents were interviewed using the ICD-10 Symptom Checklist, and patients
      additionally with psychopathology rating scales. Internal consistency of the TBDI
      distress index was 0.92. A cutoff of 2.0 was associated with 96% sensitivity and
      56% specificity. Mean TBDI scores were significantly lower for nonpatients than
      for both outpatients and inpatients, and for schizophrenic patients compared with
      patients suffering from schizoaffective/mood disorders and from
      neurotic/personality disorders. The TBDI shows good capacity to discriminate
      levels and symptoms of distress between control subjects and mentally ill
      patients. The TBDI is a brief, valid, and useful tool for stress-related research
      that allows comparison of the psychological responsiveness of distinct patients
      and groups of patients and facilitates assessment of distress levels across
      cultural or language barriers.

PMID- 11994844
TI  - Reliability and validity of the Korean version of the Temperament and Character
      Inventory.
AB  - The purpose of this study was to evaluate the reliability and validity of the
      Korean version of the Temperament and Character Inventory (TCI), a self-report
      questionnaire based on Cloninger's biosocial model of personality. The TCI was
      translated into Korean and administered to 851 Korean college students. A test
      retest study of the TCI was conducted across a 3-month interval with 130
      subjects. Internal consistency was calculated by Cronbach alpha. Test-retest
      reliability was analyzed by Pearson correlation analysis. Factor analyses for the
      temperament and character dimensions were performed using principal component
      analysis, rotating factors obliquely by promax. A comparison of TCI scores
      between Korean and United States college students was done using independent t
      tests. Cronbach alpha values for the TCI scales ranged from.60 to.85 for the
      temperament scales and from.82 to.87 for the character scales. Test-retest
      correlations (r) ranged from.52 to.72 for the temperament scales and from.52
      to.71 for the character scales. Principal component factor analyses showed
      similar factor structures of four temperaments and three characters as the
      American version of the TCI, except for the Reward Dependence and Persistence
      temperament scales. Explorative factor analysis with a condition of eigenvalue
      greater than 1 produced five factors, as compared to seven factors extracted in
      Cloninger's original report. Results using a preset seven-factor solution was
      forced and did not successfully extract Cloninger's seven factors. Korean college
      students had higher mean scores on Harm Avoidance and lower mean scores on the
      rest of the scales as compared to a sample of US college students. The results of
      this study confirm that the Korean TCI has satisfactory psychometric properties
      and reflects Cloninger's biosocial model of personality.

PMID- 11994845
TI  - Comparison of insertion time and pullout strength between self-tapping and non
      self-tapping AO 4.5-mm cortical bone screws in adult equine third metacarpal
      bone.
AB  - OBJECTIVE: To compare screw insertion characteristics and pullout mechanical
      properties between self-tapping (ST) and non-self-tapping (NST) AO 4.5-mm
      cortical bone screws in adult equine third metacarpal bone (MC3). STUDY DESIGN:
      In vitro biomechanical experiment. ANIMALS OR SAMPLE POPULATION: Seven pairs of
      adult equine MC3. METHODS: Bicortical holes were drilled transversely in proximal
      metaphyseal, diaphyseal, and distal metaphyseal locations of paired MC3. NST
      screws were inserted in pre-tapped holes in 3 sites of one bone pair, and ST
      screws were inserted in non-tapped holes of contralateral MC3. Tapping and screw
      insertion times and maximum torques were measured. Screw pullout mechanical
      properties were determined. RESULTS: Screw insertion time was longer for ST
      screws. Total time for tapping and insertion (total insertion time) was over
      twice as long for NST screws. Statistically significant differences were not
      observed between screws for any pullout mechanical property. From pullout tests,
      diaphyseal locations had significantly stiffer and stronger structure than
      metaphyseal locations. Pullout failure more commonly occurred because of screw
      breakage than bone failure. Bone failure and bone comminution were more commonly
      associated with ST screws. Bone failure sites had pullout failure loads that were
      90% of screw failure sites. CONCLUSIONS: NST and ST 4.5-mm-diameter cortical bone
      screws have similar pullout mechanical properties from adult equine MC3. ST
      screws require less than half the total insertion time of NST screws. CLINICAL
      RELEVANCE: Use of ST 4.5-mm-diameter cortical bone screws should be considered
      for repair of adult equine MC3 fractures; however, bone failures at screw sites
      should be monitored.

PMID- 11994846
TI  - Arthroscopic removal of dorsoproximal chip fractures of the proximal phalanx in
      standing horses.
AB  - OBJECTIVE: To report a technique for, and outcome after, arthroscopic removal of
      dorsoproximal chip fractures of a proximal phalanx in standing horses. STUDY
      DESIGN: Retrospective study. ANIMALS OR SAMPLE POPULATION: A total of 104 horses,
      1 to 13 years of age, with a dorsoproximal chip fracture of a proximal phalanx.
      METHODS: Horses were restrained in standing stocks and sedated with intravenous
      xylazine, detomidine, or a combination of both drugs. Local analgesia was
      achieved with 2% mepivacaine administered intra-articularly and by subcutaneous
      infiltration in a crescent-shaped block dorsal to the fetlock. Sterile drapes
      were placed on the surgical field, and impervious drapes were used on the hoof
      and floor. Arthroscopic portals were created in the dorsal pouch of the
      metacarpophalangeal or metatarsophalangeal joints to remove chip fractures.
      Statistical analysis was performed on race records for all Thoroughbred
      racehorses and compared with previously published studies. Operative and
      hospitalization times were compared with those of the general hospital
      population, and risks associated with general anesthesia were examined. RESULTS:
      No major operative or postoperative complications occurred. Ninety-one percent of
      racehorses raced after surgery with 78% returning to race at the same or higher
      level. CONCLUSION: Standing arthroscopic surgery can be performed successfully to
      remove dorsoproximal chip fractures of the proximal phalanx. CLINICAL RELEVANCE:
      Standing arthroscopic surgery is a valid alternative treatment for experienced
      surgeons to avoid the expense and potential risks associated with general
      anesthesia.

PMID- 11994847
TI  - A biomechanical comparison of equine third metacarpal condylar bone fragment
      compression and screw pushout strength between headless tapered variable pitch
      and AO cortical bone screws.
AB  - OBJECTIVES: To compare bone fragment compression and the mechanical pushout
      strength and stiffness of 6.5-mm Acutrak Plus (AP) and 4.5-mm AO cortical (AO)
      bone screws after stabilization of a simulated equine third metacarpal (MC3) bone
      complete lateral condylar fracture. STUDY DESIGN: In vitro biomechanical paired
      study of screw insertion variables, bone fragment compression, and screw pushout
      tests using a bone screw stabilized simulated lateral condylar fracture model.
      SAMPLE POPULATION: Six pairs of cadaveric equine MC3s. METHODS: Metacarpi were
      placed in a fixture and centered on a biaxial load cell in a materials testing
      system to measure torque, compressive force, and time for drilling, tapping, and
      screw insertion. Fragment compression was measured with a pressure-sensing device
      placed between the simulated fracture fragments during screw insertion for
      fragment stabilization. Subsequently, screws were pushed out of the stabilized
      bone fragments in a single cycle to failure. A paired t test was used to assess
      differences between site preparation, screw insertion, fragment compression, and
      screw pushout variables, with significance set at P <.05. RESULTS: Measured
      drilling variables were comparable for AO and AP specimens. However, the AP tap
      had significantly greater insertion torque and force. Mean maximum screw
      insertion torque was significantly greater for AO screws. For fragment
      compression, AP screws generated 65% and 44% of the compressive pressure and
      force, respectively, of AO screws. AP screws tended to have higher overall
      pushout strength. Pushout stiffness was similar between both screw types.
      CONCLUSION: The 6.5-mm tapered AP screw generated less interfragmentary
      compressive pressure and force but had similar pushout stiffness. Evaluation of
      failure patterns demonstrated that AP screws had greater pushout strength
      compared with 4.5-mm AO screws for fixation of a simulated complete lateral
      condylar fracture. CLINICAL RELEVANCE: The 6.5-mm tapered AP screw should provide
      ample holding strength but would provide less interfragmentary compression than
      4.5-mm AO screws for repair of complete lateral condylar fractures in horses.

PMID- 11994848
TI  - An in vitro biomechanical investigation of an MP35N intramedullary interlocking
      nail system for repair of third metacarpal fractures in adult horses.
AB  - OBJECTIVE: To compare monotonic mechanical properties of gap-ostectomized third
      metacarpal bones (MC3) stabilized with an MP35N interlocking nail system with
      contralateral intact bones. ANIMALS OR SAMPLE POPULATION: Twenty-four pairs of
      cadaveric equine MC3s. METHODS: Third metacarpal bones were divided into 4
      mechanical testing groups (6 pairs per group): compression, palmarodorsal (PD)
      and mediolateral (ML) 4-point bending, and torsion. One MC3 from each pair was
      randomly selected as an intact specimen, and the contralateral gap ostectomized
      bone was stabilized with a 4-hole, 14-mm-diameter, 250-mm-long, MP35N
      intramedullary nail, and four, 7-mm-diameter, 60-mm-long MP35N interlocking
      screws (constructs). Mechanical testing properties were compared between intact
      specimens and constructs with a paired t test (significance set at P <.05).
      RESULTS: Intact specimens were significantly stronger and stiffer than constructs
      in all testing modes except PD bending. Constructs achieved mean yield strengths
      that were 57% (compression), 81% (PD bending), 68% (ML bending), and 78% (torque)
      of intact specimens. Constructs achieved mean stiffnesses that were 53%
      (compression), 58% (PD bending), 41% (ML bending), and 47% (torque) of intact
      specimens. CONCLUSION: Monotonic yield mechanical properties of MP35N
      intramedullary interlocking nail-stabilized, gap-ostectomized MC3 were lower than
      those of paired intact bones but exceeded reported in vivo loads for dorsopalmar
      bending and compression and estimated in vivo torsional loads. CLINICAL
      RELEVANCE: Considering the benefits associated with intramedullary interlocking
      nail fixation of fractures, this system should be considered for use for repair
      of MC3 fractures with applicable fracture configurations.

PMID- 11994849
TI  - Intraventricular tension pneumocephalus as a complication of transfrontal
      craniectomy: a case report.
AB  - OBJECTIVE: To report the diagnosis and surgical treatment of a case of
      intraventricular tension pneumocephalus in a dog after a transfrontal craniectomy
      for removal of a falx cerebri meningioma. STUDY DESIGN: Case report. ANIMAL: A 12
      year-old spayed English springer spaniel. RESULTS: Intraventricular air and a
      fistula between the craniectomy site and ventricular system were identified by
      magnetic resonance imaging. Prompt repair of the dural defect using prosthetic
      dura mater resulted in immediate regression of the neurological signs and
      cerebral spinal fluid rhinorrhea. Magnetic resonance imaging repeated 8 weeks
      after surgery showed complete resolution of pneumocephalus. CONCLUSIONS AND
      CLINICAL RELEVANCE: Tension pneumocephalus is an uncommon but life-threatening
      complication of craniectomy that requires urgent diagnosis and treatment.

PMID- 11994850
TI  - Epidural morphine and detomidine decreases postoperative hindlimb lameness in
      horses after bilateral stifle arthroscopy.
AB  - OBJECTIVE: To determine whether preoperative epidural administration of morphine
      and detomidine would decrease postoperative lameness after bilateral stifle
      arthroscopy in horses. STUDY DESIGN: Prospective clinical controlled study.
      ANIMALS: Eight adult horses that had bilateral arthroscopic procedures, including
      drilling of cartilage and subchondral bone within the femoropatellar joints.
      METHODS: Horses were randomly separated into 2 groups. Preoperatively, 4 horses
      were administered a combination of epidural morphine (0.2 mg/kg) and detomidine
      (30 microg/kg), and 4 horses were administered an equivalent volume of epidural
      saline (0.9% NaCl) solution. Postoperative pain was assessed using 6 video
      recordings made at hourly intervals of each horse at a walk. Assessments began 1
      hour after recovery from anesthesia. The recordings were scrambled out of
      sequence and evaluated by 3 observers, unaware of treatment groups, who scored
      lameness from 0 to 4. Lameness scores of the 2 groups of horses were compared
      using a Wilcoxon's rank sum test. Heart and respiratory rates were also measured
      at each hourly interval and compared between groups using a repeated-measures
      ANOVA; statistical significance was set at P <.05. RESULTS: Preoperative
      administration of epidural morphine and detomidine significantly decreased
      lameness and heart rates after bilateral stifle arthroscopy. The greatest
      decrease was detected at hours 1 and 2 after recovery from anesthesia.
      CONCLUSION: We conclude that horses undergoing a painful arthroscopic procedure
      of the stifle joint benefit from the administration of preoperative epidural
      morphine and detomidine. CLINICAL RELEVANCE: Preoperative epidural administration
      of detomidine and morphine may be useful in decreasing postoperative pain after
      stifle arthroscopy as well as pain associated with other painful disorders
      involving the stifle joint, such as septic arthritis and trauma.

PMID- 11994851
TI  - Evaluation of a vessel-sealing device for use in laparoscopic ovariectomy in
      mares.
AB  - OBJECTIVE: To evaluate a vessel-sealing instrument (LigaSure) as a method for
      hemostasis of the ovarian vasculature. STUDY DESIGN: Prospective study. ANIMALS
      OR SAMPLE POPULATION: Thirteen mares (8 experimental, 5 patients), aged 2 to 20
      years and weighing 405 to 500 kg. METHODS: Thirteen mares had standing bilateral
      laparoscopic ovariectomy using a vessel-sealing device (LigaSure) to provide
      hemostasis. Eight reproductively normal experimental mares were divided into 2
      groups: 1 group was re-examined laparoscopically 72 hours and the other group 10
      days after the initial standing laparoscopic ovariectomy. The vessel-sealing
      device uses high current and low voltage, along with pressure, to reorganize the
      collagen into a translucent seal to achieve hemostasis of the ovarian
      vasculature. RESULTS: No major operative or postoperative complications were
      encountered. Complete hemostasis of the ovarian pedicle was accomplished. One
      mare had a fever for 24 hours' postoperatively; this responded to a single dose
      of flunixin meglumine. CONCLUSIONS: The LigaSure appears to be a safe method for
      hemostasis of the ovarian vasculature. CLINICAL RELEVANCE: Benefits of the
      LigaSure include no foreign material remaining in the abdomen and minimal to no
      need for surgical dissection before application. The LigaSure eliminates
      complications with potential ligature slippage and bleeding during dissection.

PMID- 11994852
TI  - Endoscopic-assisted disruption of urinary calculi using a holmium:YAG laser in
      standing horses.
AB  - OBJECTIVE: To describe a technique for endoscope-assisted disruption and removal
      of urinary calculi using a holmium:YAG laser in sedated, standing horses. STUDY
      DESIGN: Retrospective study. ANIMALS: Six horses with urinary calculi. METHODS: A
      holmium:YAG laser was used to disrupt naturally occurring urinary calculi in
      horses (4 geldings, 1 stallion, 1 mare). Ischial urethrotomy was performed in
      male horses to provide a portal for the endoscope and laser fiber. Calculus
      fragments were removed by a combination of lavage, transendoscopic basket snare
      removal, forceps, and digital manipulation. Ischial urethrotomies healed by
      second intention. Follow-up was obtained by recheck examination and telephone
      interview of owners. RESULTS: No major operative or postoperative complications
      occurred. Two calculi (1 stallion and 1 mare) were fragmented by a combination of
      laser ablation and manual disruption with a lithotrite. Postoperative dysuria
      occurred in the mare, but resolved after 1 month. Mean (+/- SD) follow-up was 306
      +/- 149 days; no other complications were reported. CONCLUSIONS: Calcium
      carbonate urinary calculi (up to 15 cm in diameter) in horses can be effectively
      fragmented with a holmium:YAG laser. It is not known if this technique would be
      completely effective for larger calculi or extremely dense calculi. CLINICAL
      RELEVANCE: Calculus disruption by an endoscopically assisted holmium:YAG laser
      offers a minimally invasive method that can be performed in standing horses and
      that minimizes patient risk.

PMID- 11994853
TI  - Experimental evaluation of urinary bladder marsupialization in male goats.
AB  - OBJECTIVE: To evaluate the outcome of urinary bladder marsupialization in male
      goats. STUDY DESIGN: Prospective, experimental study. ANIMALS: Six healthy mixed
      breed male goats. METHODS: After experimentally induced urethral obstruction, 6
      male goats had urinary bladder marsupialization. Renal ultrasonography, complete
      blood count, and serum biochemical analysis were evaluated preoperatively (day
      0), at 7 postoperative days, and then at 30-day intervals until 180 days. Stomal
      diameter was recorded immediately postoperatively and at each postoperative
      interval. Necropsy examination was performed on day 180 or when stomal stricture
      or death occurred. RESULTS: Stomal stricture occurred in 1 goat at 120 days.
      Another goat was found dead at 150 days; severe, suppurative cystitis was
      identified on necropsy. All goats had mild urine scald dermatitis. Serum
      biochemical values remained within normal limits, but significant decreases in
      white blood cell count, serum creatinine concentration, and stomal diameter
      occurred. At necropsy, all bladders were tubular in shape. Histological evidence
      of chronic suppurative cystitis and chronic, mild lymphoplasmacytic pyelitis
      occurred in all goats. Bacterial culture of renal tissue yielded growth in 3
      goats, and bladder mucosal swabs yielded bacterial growth in all goats.
      CONCLUSIONS: Although clinical signs of ascending urinary tract infection were
      not observed in goats with patent stomata, urinary bladder marsupialization may
      result in ascending urinary tract inflammation or infection. CLINICAL RELEVANCE:
      Based on our results, urinary bladder marsupialization should be recommended with
      caution as the primary method for management of urinary tract obstruction in
      clinical cases.

PMID- 11994854
TI  - Postoperative rupture of an aortic aneurysmal dilation associated with a patent
      ductus arteriosus in a dog.
AB  - OBJECTIVE: To describe an unusual case of fatal aortic aneurysm rupture after
      standard ligation of a left-to-right shunting patent ductus arteriosus (PDA) and
      review the literature concerning the causes of aneurysm and applicable medical
      physics of blood flow that may contribute to mural failure. STUDY DESIGN:
      Clinical case report. SAMPLE POPULATION: An 11-month-old female Brittany spaniel.
      RESULTS: A PDA was diagnosed in the dog after referral for a grade IV/IV cardiac
      murmur. Diagnostic tests performed included a minimum database, thoracic
      radiography, and echocardiography. Conventional surgical ligation of the PDA was
      performed. The postoperative recovery from anesthesia was uneventful.
      Approximately 5 hours after surgery, the dog vocalized once and collapsed. All
      resuscitative efforts failed. Necropsy showed a large, spiral rupture of the
      cranial and dorsal wall of the aorta that extended from the left subclavian
      artery to 2 cm distal to the PDA-aorta junction. No evidence of intramural,
      perianeurysmal hemorrhage or inflammation was noted. Histopathologic examination
      of the ruptured aneurysm showed that the wall lacked a defined tunica intima and
      endothelial cell layer. A distinct separation of the thinned tunica media
      parallel to the elastic fibers was noted. CONCLUSIONS AND CLINICAL RELEVANCE:
      Dilatation of the aorta near the area of a PDA is one of the recognized
      abnormalities associated with the condition. Aneurysmal dilatation results from
      and contributes to abnormal blood flow dynamics and increased aortic wall
      tension, which promotes expansion. Although an unusual and previously unreported
      sequela, rupture of the aneurysm should be considered a possible complication
      when ligation of a PDA with a conspicuous aortic aneurysmal dilation is
      performed.

PMID- 11994855
TI  - Preliminary observations on expression of transforming growth factors beta1 and
      beta3 in equine full-thickness skin wounds healing normally or with exuberant
      granulation tissue.
AB  - OBJECTIVE: To determine whether transforming growth factor (TGF)-beta1 and -beta3
      expression differs between equine limb wounds healing normally and those healing
      with experimentally induced exuberant granulation tissue (EGT). STUDY DESIGN: Six
      wounds were created on the lateral aspect of both metacarpi of each horse; one
      forelimb was untreated, and the other was bandaged to stimulate the development
      of EGT. Sequential wound biopsies allowed comparison of growth factor expression
      between the two types of wound. ANIMALS: Four horses (2 to 4 years of age; 350 to
      420 kg). METHODS: Wounds were assessed grossly, histologically, and by enzyme
      linked immunosorbent assay (ELISA) for TGF-beta1 and -beta3 expression at 12 and
      24 hours and 2, 5, 10, and 14 days postoperatively. RESULTS: Bandaged wounds
      developed EGT. In all wounds, TGF-beta1 peaked early and remained elevated at 14
      days. Peak TGF-beta1 concentration was higher in wounds with EGT, but not
      significantly so. Expression of TGF-beta3 differed from TGF-beta1, with peak TGF
      beta3 concentrations being delayed. Concentrations of TGF-beta3 were higher in
      wounds healing normally, but this difference was not significant. CONCLUSIONS:
      During both normal and exuberant wound repair, the expression of TGF-beta1
      occurred earlier than TGF-beta3 expression. Wounds healing with EGT tended to
      have higher concentrations of fibrogenic TGF-beta1 and lower concentrations of
      antifibrotic TGF-beta3 than wounds healing normally, although these differences
      were not statistically significant. CLINICAL RELEVANCE: This study suggests that
      the production of EGT in bandaged wounds may be related to increased expression
      of fibrogenic TGF-beta1 and decreased expression of antifibrotic TGF-beta3.
      Further investigation of the roles of TGF-beta1 and -beta3 may be important in
      understanding the molecular control of EGT in horses.

PMID- 11994856
TI  - Temporal localization of immunoreactive transforming growth factor beta1 in
      normal equine skin and in full-thickness dermal wounds.
AB  - OBJECTIVE: To describe the localization of immunoreactive transforming growth
      factor (TGF)-beta1 in both normal skin and full-thickness dermal wounds of the
      limb and the thorax of the horse. STUDY DESIGN: Six full-thickness excisional
      wounds were created on the lateral aspect of one metacarpal region and on the
      midthoracic area of each horse. Sequentially collected tissue specimens from
      wound margins were assessed for TGF-beta1 expression by immunohistochemistry.
      ANIMALS: Four horses (2 to 4 years of age). METHODS: A neutralizing monoclonal
      anti-human TGF-beta1 antibody was used to detect the spatial expression of TGF
      beta1 protein by immunohistochemical localization in biopsies obtained before
      wounding and at 12 and 24 hours, and 5, 10, and 14 days. RESULTS: No differences
      in localization of immunoreactive TGF-beta1 were detected between limb and
      thorax, for either intact skin or wounds. Unwounded epidermis stained moderately
      for TGF-beta1 protein throughout all layers, whereas the dermis was relatively
      devoid of immunoreactivity. During the acute stage of repair, migrating
      epithelium lost its stain, whereas cells of epidermal appendages remained
      strongly immunoreactive. The epithelium recovered its TGF-beta1 immunoreactivity
      during wound remodeling, although cells of the stratum corneum remained negative.
      Macrophages of the inflammatory exudate had positive cytoplasmic staining that
      diminished with time. Immunoreactivity of granulation tissue fibroblasts was
      evident early on and increased throughout the repair process. CONCLUSIONS: TGF
      beta1 is constitutively expressed in normal, unwounded equine epithelium. Its
      expression is upregulated within the skin on injury and is associated with the
      cells involved in wound repair. CLINICAL RELEVANCE: A more precise understanding
      of the temporal and spatial expression of TGF-beta1 during wound repair in horses
      should provide the groundwork for possible future manipulations of both normal
      and aberrant tissue repair.

PMID- 11994857
TI  - The effects of ethylene oxide and gas-plasma sterilization on failure strength
      and failure mode of pre-tied monofilament ligature loops.
AB  - OBJECTIVE: To evaluate the effects of ethylene oxide and gas-plasma sterilization
      on the failure strength and failure mode of pre-tied monofilament ligature loops.
      STUDY DESIGN: A randomized block design was used by blocking for suture (size 1
      polyglyconate, size 2 polydioxanone) and sterilization technique (control,
      ethylene oxide, gas plasma). SAMPLE POPULATION: Twenty replicates of each suture
      sterilization technique combination. METHODS: Ligature loops were pre-tied using
      a 4S-modified Roeder knot then exposed to 1 of 3 treatments (control, ethylene
      oxide, or gas-plasma sterilization). Ligature loops were mounted onto a
      mechanical testing machine to evaluate the effects of sterilization on failure
      strength and failure mode (disruption, untying). RESULTS: There were no
      differences between polydioxanone and polyglyconate suture materials in failure
      strength or mode within sterilization methods. Both sterilization methods
      significantly increased the likelihood that suture loops would untie compared
      with controls subjects. Ligature loops that disrupted had a greater breaking
      strength than those that untied, regardless of sterilization method or suture
      type. CONCLUSIONS/CLINICAL RELEVANCE: Sterilization with either ethylene oxide or
      gas plasma of pre-tied, polyglyconate, or polydioxanone ligature loops
      significantly increases the in vitro likelihood of a modified Roeder knot
      untying. Further studies need to be conducted to determine the in vivo
      requirements for ligature loops.

PMID- 11994860
TI  - Strategies to treat protein-losing enteropathy.
AB  - Protein-losing enteropathy (PLE), excessive serum protein loss within the
      gastrointestinal tract, after Fontan operation is a poorly understood disorder.
      Reported to occur anywhere from weeks to years after Fontan operation, there are
      no identifiable risk factors for its development, and its clinical manifestations
      vary widely from significant morbidity and mortality to mild-to-moderate
      hypoproteinemia with minimal functional impairment. Treatment strategies,
      tailored to the severity of the disease, include symptomatic relief with
      diuretics and supplemental protein, attempts at halting intestinal protein leak
      using steroids or heparin, and alteration of cardiovascular physiology via
      fenestration creation, atrial pacing, or heart transplantation. A better
      understanding of the pathophysiology of PLE will allow the development of more
      effective treatment modalities. We hypothesize an abnormality of local intestinal
      circulation in patients with PLE that may be related to low cardiac output.
      Compensatory flow redistribution takes place under conditions of low cardiac
      output. We studied superior mesenteric artery flow using Doppler ultrasound in 40
      patients after Fontan operation, 13 of whom had clinical signs of PLE, and
      compared them with 25 normal control patients. Diastolic velocities were lower in
      Fontan subjects, and the ratio of systolic-to-diastolic velocities and the
      resistance index were higher in Fontan patients compared with the control group.
      Patients with PLE after Fontan operation had higher systolic-to-diastolic
      velocities and resistance index than patients with Fontan and no active PLE.
      However, subjects with Fontan circulation but without PLE had higher indices of
      mesenteric resistance than the normal controls, suggesting an abnormality of the
      mesenteric circulation even in those without overt signs of PLE. It is plausible
      to postulate that activation of the renin-angiotensin system with increased
      levels of circulating angiotensin II may be responsible for the increase in
      mesenteric vascular resistance seen after Fontan operation, thereby placing these
      patients at risk for development of PLE.

PMID- 11994861
TI  - The beneficial effects of total cavopulmonary conversion and arrhythmia surgery
      for the failed Fontan.
AB  - Postoperative Fontan patients can develop hemodynamic abnormalities and
      refractory atrial arrhythmias resulting in significant morbidity and mortality.
      We present our experience with total cavopulmonary artery conversion and
      arrhythmia surgery. Between 1994 and 2001, 41 patients underwent total
      cavopulmonary artery conversion and arrhythmia surgery. Significant hemodynamic
      lesions were repaired concomitantly: aortic aneurysm (n=1), atrioventricular
      valve insufficiency (n=8), and pulmonary artery stenosis (n=9). Thirty-five
      patients were in New York Heart Association class III or IV. Mean age at original
      Fontan was 7.5+/-6.5 years, at Fontan conversion, 18.7+/-9.0 years. Arrhythmia
      surgery for atrial re-entry tachycardia evolved from isthmus cryoablation (n=10)
      to right-sided maze (n=17). Maze-Cox III was used for 14 patients with atrial
      fibrillation. Atrial (n=34) and dual chamber (n=5) pacemakers were placed.
      Mortality and reoperation for bleeding rates are 0%. Chest tubes were removed on
      postoperative day 9.0+/-6.0. Mean hospital stay was 11.8+/-6.6 days. Three
      patients required cardiac transplantation at 8 days, 9 months, and 33 months
      postoperatively. There was one long-term death from acute myocardial infarction 2
      years postoperatively. For the entire series, arrhythmia recurrence is 12.2%
      (5/41). Only 9.8% of patients (4/41) receive chronic antiarrhythmic medications;
      these patients were among the first eight in the series. Most patients are in New
      York Heart Association I or II. Bruce protocol in 12 patients showed increased
      tolerance (P<.05) Total cavopulmonary artery conversion with concomitant
      arrhythmia surgery is excellent therapy for patients with failed Fontan. It is
      safe, improves New York Heart Association class, improves exercise tolerance, and
      the incidence of recurrent arrhythmias is low.

PMID- 11994862
TI  - Complications associated with heterotaxy syndrome in Fontan patients.
AB  - Enormous progress has been made in the last decade toward decreasing the risk of
      the Fontan operation and optimizing early and intermediate outcomes. Heterotaxy
      syndrome patients, with their extensive constellation of anatomic abnormalities,
      constitute a challenging group to manage surgically. Palliative procedures early
      in life are directed at creation of a satisfactory balance between pulmonary and
      systemic blood flow and at the same time assurance of unobstructed pulmonary
      venous return. For heterotaxy patients who survive beyond the newborn period, and
      are considered to have nonseptatable hearts, early reduction of the volume load
      of the functional single ventricle is extremely important. Early conversion from
      parallel pulmonary and systemic circulations to a superior cavopulmonary
      anastomosis (bidirectional Glenn or hemi-Fontan) is the preferred strategy.
      Traditionally, those patients with heterotaxy who survive initial surgical
      management have been considered a very high-risk population with respect to an
      eventual Fontan procedure. In heterotaxy patients it is particularly important to
      understand the unique and variable anatomy of the sinus node and conduction
      system, the potential for occult pulmonary venous obstruction, the tendency for
      development of atrioventricular valve regurgitation in volume loaded ventricles,
      and the potential for recurrent or persistent cyanosis because of intrahepatic
      shunting or pulmonary arteriovenous malformations.

PMID- 11994863
TI  - Thromboembolic problems after the Fontan operation.
AB  - One of the major causes of morbidity and mortality after the Fontan operation is
      thromboembolic events (TE). To assess the current knowledge of TE after Fontan
      surgery, a comprehensive MEDLINE search of the English literature from 1971 to
      2000 was conducted using the key words Fontan, univentricular heart, children,
      thrombosis, congenital heart disease, cavopulmonary, and palliation. Other
      relevant publications were identified from bibliographies of the literature
      retrieved. Fifty-one studies were identified and analyzed for incidence,
      potential morbidity and mortality, risk factors, prophylactic options, and
      risk/benefit ratio of prophylactic anticoagulation as relates to TE after Fontan
      surgery. There were 23 case reports, 13 retrospective cohort studies that
      included some details about TE among other reported outcomes after Fontan
      procedures, eight retrospective cohort studies in which TE was the primary
      outcome measure, and seven articles reporting cross-sectional point surveys, only
      three of which directly surveyed TE as an outcome. Based on an analysis of the
      current literature, there is insufficient evidence to make clear recommendations
      about optimal anticoagulant prophylaxis at this time. Multicenter randomized
      controlled trials comparing prophylactic antiplatelet with anticoagulation
      therapies are needed to provide rational scientific guidelines for future
      management of Fontan patients.

PMID- 11994864
TI  - Management of aortopulmonary collateral arteries in Fontan patients: occlusion
      improves clinical outcome.
AB  - Children with chronic cyanotic heart disease often develop systemic-to-pulmonary
      artery collateral vessels that can be deleterious at the time of a Fontan
      procedure because of excessive pulmonary blood flow with resultant ventricular
      volume overload. We therefore occlude all significant collateral arteries during
      preoperative cardiac catheterization. From June 1993 to September 2001, 137
      children ranging from 1.5 to 18.3 years old (median, 2.4 years), underwent a
      fenestrated lateral tunnel Fontan procedure. Of these, 130 (95%) had a previous
      bidirectional Glenn anastomosis, including 43 (31%) with a Norwood procedure.
      Preoperatively, 52 children (38%) required occlusion of collateral vessels. Two
      of five perioperative deaths (operative survival, 96%) resulted from excessive
      pulmonary blood flow; one from unrecognized collateral arteries and one from
      uncontrollable collateral arteries. Postoperatively, 29 children (22%) required
      coil occlusion of collateral vessels for elevated pulmonary artery pressures,
      heart failure, or prolonged chest tube drainage. At follow-up of 1.5 months to
      8.3 years (mean, 4.1 years), there have been four late deaths (two from
      pneumonia, two secondary to heart failure); nine patients underwent cardiac
      transplantation for refractory heart failure. Ten of 11 patients with ventricular
      failure required occlusion of significant collateral vessels postoperatively.
      Hemodynamically significant collateral arteries are common in Fontan candidates.
      Aggressive control can result in good early and medium-term survival. After the
      Fontan operation, the presence of significant collateral vessels may be a marker
      for eventual cardiac failure; 11 of the 29 patients who required postoperative
      coil placement went on to transplantation or died of heart failure.

PMID- 11994865
TI  - Management of aortopulmonary collateral arteries in Fontan patients: routine
      occlusion is not warranted.
AB  - Aortopulmonary collaterals (APCs) are common in patients undergoing a Fontan
      operation and are typically identified at cardiac catheterization. However, this
      is a qualitative approach and has important limitations. Previous catheterization
      based studies of the effects of APCs have produced conflicting results. We have
      recently carried out a study directly measuring APC flow at the time of Fontan
      operation. This study showed that patients undergoing a Fontan operation have APC
      flow many-fold higher than controls, the extent of APC flow varies widely from
      patient to patient, APC flow does not increase in a linear fashion over time, and
      that APC flow has no detectable effect on the outcome of the Fontan operation.
      Thus, routine preoperative APC identification and occlusion does not appear
      indicated. A randomized study of preoperative coil occlusion could clarify this
      issue further. Aortopulmonary collaterals may exert a "threshold" effect,
      increasing risk in patients who also have other risk factors. Preoperative coil
      occlusion may decrease overall risk in such patients. Postoperative APC occlusion
      is a reasonable option in the patient with prolonged effusions after a Fontan
      operation, with no other correctable anatomic defects.

PMID- 11994866
TI  - Fontan operation for patients with severe distal pulmonary artery stenosis,
      atresia, or a single lung.
AB  - In the absence of a ventricular pump, the status of the pulmonary circulation is
      crucial to the success of the Fontan operation. In an updated version (1999) of
      the optimal criteria for the Fontan operation, several of these criteria address
      the pulmonary circulation: pulmonary artery pressure, pulmonary vascular
      resistance, pulmonary artery size, and absence of significant pulmonary artery
      branch stenosis. This chapter reviews the role of the pulmonary circulation in a
      successful Fontan operation, with a particular emphasis on surgical techniques to
      repair severe distal or hilar pulmonary artery stenosis or atresia. The special
      situation of the patient with a single pulmonary artery is also addressed. Severe
      hilar pulmonary artery stenosis or atresia can be repaired by the technique of
      intrapulmonary pulmonary artery reconstruction with pericardial patch or tube and
      allow the successful completion of the Fontan operation. In the selected patient
      with a single pulmonary artery and optimal hemodynamics, the Fontan operation is
      possible with good outcome. However, further experience is needed in a larger
      number of patients to assess the long-term outcome of these treatment strategies.

PMID- 11994867
TI  - Deep hypothermic circulatory arrest: current status and indications.
AB  - A number of groups have directed clinical and laboratory research efforts to
      define and delineate the limits of hypothermic circulatory arrest. The
      deleterious effects of cardiopulmonary bypass in small children are reviewed to
      place into historical perspective the impetus behind the development of
      hypothermic circulatory arrest. Among the advantages of deep hypothermic
      circulatory arrest are decreased exposure to cardiopulmonary bypass with its
      sequelae, improved operative field exposure, avoidance of multiple cannulas, and
      reduced postoperative edema. Because of concern regarding the effectiveness of
      the neurologic protection afforded by deep hypothermic circulatory arrest, a body
      of literature has developed that includes both clinical (eg, the Boston
      Circulatory Arrest Study) and laboratory investigations of the influence of pH
      strategy, hematocrit level, oxygen strategy, intermittent reperfusion, and their
      interaction on outcome measures. Concomitantly, changes in both cardiopulmonary
      bypass and circulatory arrest techniques have led surgeons to reconsider the
      indications for deep hypothermic circulatory arrest use in children. In the
      future it will be important to focus an equal degree of attention to refine
      methods of continuous cardiopulmonary bypass including innovative methods that
      allow avoidance of circulatory arrest. No clear guidelines are presently
      available for the congenital surgeon regarding how low flow can be reduced, at
      what temperature repair should be undertaken, and what duration of low flow can
      be used for particular circumstances of pH, hematocrit, and collateral return.
      Until this information is collected, the comprehensive information regarding
      circulatory arrest that has already been gathered allows this technique to be
      used more safely than innovative but unproven methods of continuous
      cardiopulmonary bypass.

PMID- 11994868
TI  - Arch reconstruction without circulatory arrest: historical perspectives and
      initial clinical results.
AB  - For many years, deep hypothermic circulatory arrest had been a necessary and
      unavoidable adjunct to surgical procedures including aortic arch reconstruction
      in neonates and infants. Despite meticulous investigation of bypass techniques
      for deep hypothermic circulatory arrest, unfavorable long-term neurologic
      deficits have been well documented. Currently, several cerebral perfusion
      techniques are used in neonatal arch reconstruction to avoid circulatory arrest
      and prevent brain ischemia. The techniques and their initial clinical results are
      presented and related problems discussed. Currently available circulatory arrest
      techniques should be avoided in favor of well-established continuous perfusion
      techniques, even for arch reconstruction.

PMID- 11994869
TI  - Arch reconstruction without circulatory arrest: current clinical applications and
      results of therapy.
AB  - Laboratory and clinical data have confirmed the deleterious effects of deep
      hypothermic circulatory arrest. Long-term data and rigorous neuropsychiatric data
      are currently sparse, but that which are available show adverse outcomes
      following circulatory arrest, and therefore support the use of continuous
      perfusion techniques. There are no available long-term data on continuous
      perfusion techniques with respect to neurologic outcomes, but using these
      techniques the incidence of postoperative seizures or other neurologic events is
      rare. Currently available bypass systems and microsurgical techniques have
      allowed continuous flow and regional perfusion to become practical alternatives.
      Several innovative techniques for avoiding circulatory arrest during neonatal
      aortic arch reconstruction for univentricular and biventricular hearts are
      described. It would appear prudent and desirable to provide continuous perfusion
      now that long-term survival after repair of even the most complex cardiac
      anomalies including single ventricle defects is commonplace.

PMID- 11994870
TI  - Arch reconstruction without circulatory arrest: scientific basis for continued
      use and application to patients with arch anomalies.
AB  - Aortic arch hypoplasia is a common constituent of congenital heart disease. While
      repair of these lesions has been performed routinely during deep hypothermia and
      circulatory arrest, new approaches are emerging. One such approach, regional low
      flow perfusion, will be described here. This technique exploits the anticipated
      modified Blalock-Taussig shunt as a perfusion conduit. With control of the
      brachiocephalic vessels and the descending thoracic aorta, circulatory support
      can be provided to the neonate with exposure identical to that obtained by
      circulatory arrest. While first applied to children undergoing the Norwood
      operation for hypoplastic left heart syndrome, this technique has recently been
      applied to children requiring complex arch surgery in the setting of
      biventricular repair. To date, 36 neonates requiring arch reconstruction (27
      Norwood operations, 9 biventricular repairs) have been supported with regional
      low-flow perfusion. Thirty-day and hospital discharge survival has been 74%
      (20/27) for neonates undergoing Norwood operation, and 88% (8/9) for those
      undergoing biventricular repair. We will review the operative technique,
      methodologies, and clinical studies that led us to conclude that regional low
      flow perfusion provides cerebral, as well as somatic, circulatory support to the
      neonate undergoing arch reconstruction.

PMID- 11994871
TI  - Aortic arch reconstruction without circulatory arrest: review of techniques,
      applications, and indications.
AB  - The majority of neonatal intracardiac repairs can now be performed with the use
      of low-flow cardiopulmonary bypass. However, aortic arch reconstruction still
      requires a period of circulatory arrest. Recently, a number of surgeons have
      reported techniques of limiting or completely avoiding circulatory arrest during
      arch reconstruction in an attempt to reduce the risk of neurologic injury.
      Several techniques are currently in use that have been successfully applied
      during biventricular repair and the Norwood operation for a wide range of aortic
      arch pathology including hypoplastic or interrupted aortic arch, the hypoplastic
      left heart syndrome, and its equivalents. These techniques maintain continuous
      low-flow cerebral perfusion via the innominate artery, directly or indirectly. In
      the last 2 years at the Montreal Children's Hospital (Montreal, Canada) we have
      consistently used such techniques for all arch reconstructions, including the
      Norwood operation, completely avoiding the use of circulatory arrest. These
      techniques are still in evolution with regard to flow rates, temperature, and
      safe period of low flow. Although the early results are encouraging, long-term
      follow-up with respect to neurodevelopmental outcome is essential to help us
      decide which techniques are optimal. This chapter provides an overview of the
      currently used techniques allowing cerebral perfusion during aortic arch
      reconstruction and summarizes our early experience at the Montreal Children's
      Hospital.

PMID- 11994872
TI  - Virtues of a worldwide congenital heart surgery database.
AB  - The rationale for a congenital heart surgery database lies in the organized
      manner in which information can be compiled to accomplish programmatic
      evaluation, monitor clinical outcomes, comply with governmental requirements,
      perform retrospective and prospective clinical studies, and participate in local,
      national, and global improvement strategies. The task of inaugurating an
      effective congenital heart surgery database has taken many years and involved
      concurrent development efforts at multiple sites. Two such efforts took place in
      North America with the Society of Thoracic Surgeons Congenital Heart Surgery
      Database, and in Europe with the European Congenital Heart Defects Database.
      These initial efforts provided the impetus for development of an international
      congenital heart surgery database that would allow scientific exchanges on an
      international scale and promote multi-institutional evaluation of congenital
      heart surgery. Sample outcome templates from the Society of Thoracic Surgeons and
      the European Association for Cardio-thoracic Surgery's accepted minimum database
      data set are reviewed for the specific diagnostic entry ventricular septal
      defect, to familiarize the reader with potential available data summaries and
      outcome analyses, including risk stratification, when data harvest is performed.
      In Europe, the agreed upon minimum data set are now collected as part of the
      Pediatric European Cardiac Surgical Registry, while in North America users of the
      CardioAccess database and users of the minimum data set downloaded from the
      Society of Thoracic Surgeons web site are being notified of plans for a 2002 data
      harvest incorporating the minimum database data set. It is likely that the extant
      voluntary, minimal data set congenital heart surgery database will be replaced by
      a mandated system required by states, provinces, and countries. Data collection
      schemes and data validation programs will become standardized, which will result
      in improved data quality and uniform congenital heart center participation. As
      participation with valid data approaches 100% of congenital heart centers, the
      power and importance of the database increases exponentially. Reliable
      information can be used to assess residency/fellowship programs, resource
      allocation, major therapeutic trends, manpower issues, and in the end, all
      initiatives that will require accurate information.

PMID- 11994873
TI  - Practical experience with databases for congenital heart disease: a registry
      versus an academic database.
AB  - Increasingly, pooled data from multiple institutions are the source of published
      clinical results. A computerized database program is essential to compile and
      analyze clinical experience. The scope of data collection defines a database. Two
      types of databases, the registry and academic, are compared. In a registry
      database, some of the data are collected on all patients. The resources dedicated
      to data collection and entry are the practical limit to the extent of information
      in the database. The agreement on nomenclature for surgical diagnosis and
      procedure codes of congenital heart disease has paved the way for the development
      of a multi-institutional registry database. The registry database could provide a
      standard of care reference for early results after congenital heart surgery. The
      practical difficulty of data collection is obviated by limiting information to a
      basic minimum dataset. The academic database, in which all of the data are
      collected for a defined subset of patients, is designed to investigate a specific
      population of patients to generate new knowledge. It contains sufficient data to
      allow sophisticated statistical analysis to clarify the determinants of good and
      poor outcome, including early, mid- and long-term follow-up information. Multi
      institutional pooling of detailed information derived from academic databases
      will be of increasing importance in generating new knowledge to foster improved
      therapy for patients with congenital heart disease.

PMID- 11994874
TI  - The European Congenital Heart Defects Surgery Database experience: Pediatric
      European Cardiothoracic Surgical Registry of the European Association for Cardio
      Thoracic Surgery.
AB  - The initial purpose of collecting data on the outcome of congenital heart surgery
      procedures across Europe was to make possible comparison of results and
      definition of mortality and morbidity risk factors as well as targeting research
      activities. The European Congenital Heart Surgeons Foundation, established in
      1992, created the European Congenital Heart Defects Database, precursor to
      today's Pediatric European Cardiothoracic Surgical Registry. In 1999, initiatives
      of the Society of Thoracic Surgeons and the European Association for Cardio
      Thoracic Surgery resulted in a series of conferences aimed at arriving at a
      standardized nomenclature and reporting strategies as a foundation for an
      international database. In April 2000 the International Congenital Heart Surgery
      Nomenclature and Database Project published a minimum dataset of 21 items and
      lists of 150 diagnoses, 200 procedures, and 32 complications, as well as 28
      extracardiac anomalies and 17 preoperative risk factors. Since January 2000 the
      Pediatric European Cardiothoracic Surgical Registry has officially operated from
      the Department of Cardiothoracic Surgery at the Children's Memorial Health
      Institute in Warsaw, Poland, under the auspices of the European Association for
      Cardio-Thoracic Surgery and the responsibility of Bohdan Maruszewski. As of March
      2001, 84 cardiothoracic units from 33 countries had registered in the database
      and data on almost 4,000 procedures have been collected. Participation in the
      database is free of charge through the internet for all participants. Development
      of data validation protocols is a work in progress.

PMID- 11994875
TI  - Risk stratification theme for congenital heart surgery.
AB  - Surgical practice is changing and auto-evaluation of quality of care, organized
      by scientific societies, is very likely to become an obligation during this new
      decade. This evaluation requires a common nomenclature, a registry, and risk
      stratification. The primary purpose of risk stratification is to offer the
      possibility of objective analysis of surgical outcomes according to the
      complexity of the pathology treated. Registries, databases containing select
      essential data on a complete population, are not able to produce a statistically
      reliable risk stratification model. Academic databases, like that of the
      Congenital Heart Surgeons Society, contain comprehensive data on select patients,
      and are able to produce risk stratification, but only very slowly. The absence of
      risk discrimination in current registries penalizes centers treating complex
      pathologies. They may be reluctant to release their results without the security
      of risk stratification. Given the diversity of congenital heart surgery, a new
      method has been developed to stratify risks: the complexity score. This approach
      is based on the perceived opinions of a group of 50 internationally recognized
      surgeons and centers. It allows a hierarchical classification of surgical
      procedures according to mortality, morbidity, and surgical difficulty. Surgical
      procedures are scored globally on simple pathologies and in detail according to
      seven categories of risks. The complexity score in congenital heart surgery, also
      known as the Aristotle Score, is currently being developed as a collaborative
      effort of the members of the European Association for Cardio-thoracic Surgery,
      the Society of Thoracic Surgeons, the Congenital Heart Surgeons Society, and the
      European Congenital Heart Surgeons Foundation, and should be available next year.

PMID- 11994876
TI  - Software development, nomenclature schemes, and mapping strategies for an
      international pediatric cardiac surgery database system.
AB  - The field of congenital heart surgery has the opportunity to create the first
      comprehensive international database for a medical subspecialty. An understanding
      of the demographics of congenital heart disease and the rapid growth of computer
      technology leads to the realization that creating a comprehensive international
      database for pediatric cardiac surgery represents an important and achievable
      goal. The evolution of computer-based data analysis creates an opportunity to
      develop software to manage an international congenital heart surgery database and
      eventually become an electronic medical record. The same database data set for
      congenital heart surgery is now being used in Europe and North America.
      Additional work is under way to involve Africa, Asia, Australia, and South
      America. The almost simultaneous publication of the European Association for
      Cardio-thoracic Surgery/Society of Thoracic Surgeons coding system and the
      Association for European Paediatric Cardiology coding system resulted in the
      potential for multiple coding. Representatives of the Association for European
      Paediatric Cardiology, Society of Thoracic Surgeons, European Association for
      Cardio-thoracic Surgery, and European Congenital Heart Surgeons Foundation agree
      that these hierarchical systems are complementary and not competitive. An
      international committee will map the two systems. The ideal coding system will
      permit a diagnosis or procedure to be coded only one time with mapping allowing
      this code to be used for patient care, billing, practice management, teaching,
      research, and reporting to governmental agencies. The benefits of international
      data gathering and sharing are global, with the long-term goal of the continued
      upgrade in the quality of congenital heart surgery worldwide.

PMID- 11994877
TI  - Biventricular repair of double outlet right ventricle with noncommitted
      ventricular septal defect.
AB  - Double outlet right ventricle (DORV) with noncommitted ventricular septal defect
      (VSD) (DORVncVSD) represents the most extreme form of DORV, raising challenging
      surgical difficulties for biventricular repair. The considerable distance between
      the VSD and the aorta is primarily because of the very abnormal location of the
      aorta. The definition of DORVncVSD includes: (1) a VSD distant (greater than
      aortic diameter) from both arterial valves; (2) both great vessels arising fully
      from the right ventricle; and (3) a double conus. Double outlet right ventricle
      with noncommitted ventricular septal defect is a primitive right ventricle, as
      seen during embryologic development, characterized by the presence of the entire
      conotruncus from the right ventricle. One surgical technique for repair of
      DORVncVSD is rerouting of the VSD to the aorta by a long intraventricular tunnel.
      This technique is limited by the presence of conal tricuspid chordae and by the
      distance between the tricuspid and pulmonary valves, and is associated with an
      important risk of subaortic obstruction. Rerouting through the pulmonary artery
      followed by arterial switch seems a more satisfactory surgical solution. When the
      VSD is distant from the aorta, it is almost always quite close to the pulmonary
      artery. Rerouting to the pulmonary artery creates a smaller channel, and its
      application is not limited by the presence of tricuspid chordae or the tricuspid
      to-pulmonary valve distance. However, the arterial switch frequently involves
      relocating complex coronary arteries.

PMID- 11994878
TI  - Repair of congenital tracheal stenosis.
AB  - We have used six different techniques in 61 operations performed at Children's
      Memorial Hospital (Chicago, IL) between 1982 and 2001 on 54 infants with complete
      tracheal rings and primary or recurrent tracheal stenosis. Short-term and long
      term outcomes are reviewed for all techniques including pericardial
      tracheoplasty, tracheal autograft, tracheal resection, cartilage tracheoplasty,
      slide tracheoplasty, and aortic homograft patch tracheoplasty. Patients' ages
      ranged from 7 days to 72 months; mean age at operation was 6 months. There were
      33 boys and 21 girls. Associated pulmonary artery sling was present in 19 of 54
      patients (35%). Significant associated intracardiac anomaly was present in 13 of
      54 patients (24%). The number of complete tracheal rings involved ranged from two
      to 18 rings (mean, 14+/-5). All procedures were performed with the use of
      cardiopulmonary bypass. Simultaneous repair of pulmonary artery sling and cardiac
      abnormalities was undertaken. There were three early deaths, two after
      pericardial tracheoplasty and one after tracheal autograft. There were eight late
      deaths, five after pericardial tracheoplasty, one after tracheal autograft, one
      after slide tracheoplasty, and one after tracheal resection. Median length of
      hospital stay was 60 days for pericardial tracheoplasty, 28 days for tracheal
      autograft, 14 days for tracheal resection, and 18 days for the slide
      tracheoplasty. Follow-up is complete in all patients. Tracheal autograft is
      currently our procedure of choice for patients with long-segment tracheal
      stenosis because of its use of all-autologous material, technical ease of
      performance, already-present epithelial lining of the autograft, intrinsic
      maintenance of the cartilage contour, potential for growth, and ready
      availability. We limit the use of tracheal resections to patients with eight or
      less rings of tracheal stenosis.

PMID- 11994879
TI  - Postoperative management in patients with complex congenital heart disease.
AB  - Life-threatening problems occur in the neonate and infant after cardiac surgery
      because of the interplay of diminished cardiac output (CO), increased metabolic
      demand, inflammatory responses to cardiopulmonary bypass, and maladaptive
      responses to stress. Therefore, the postoperative management of patients with
      complex congenital heart defects is directed at optimization of oxygen delivery
      to maintain end-organ function and promote wound healing. Traditionally,
      assessment of circulation in the postoperative congenital heart patient has
      depended on indirect assessment of CO using parameters such as blood pressure,
      pulses, capillary refill, and urine output. Because of the limitations of
      indirect and observer-dependent assessment of CO, we rely on objective measures
      of tissue oxygen levels for the complex postoperative patient. We have found that
      continuous monitoring of the mixed venous saturation (SvO2) allows for
      identification of acute changes in systemic oxygen delivery and frequently
      precedes other indicators of decreased CO. The postoperative patient can be
      expected to have a period of decreasing CO, and the need for intervention should
      be anticipated because critical low output syndrome will develop in a subset of
      patients. Strategies for postoperative care are developed based on the diagnosis
      and procedure, but optimizing SvO2 is a consistent goal. A uniform approach to
      airway maintenance, vascular access, and drug infusions, all universal concerns
      during the perioperative period, minimizes the potential for these predictable
      and necessary interventions to result in morbidity or mortality. Management of
      the postoperative single ventricle patient targets stabilization of the systemic
      vascular resistance through the use of vasodilators to improve systemic perfusion
      and simplify ventilator management. Management of any individual patient should
      be driven by objective analysis of available data and must include efforts to re
      evaluate the treatment plan as well as to identify unanticipated problems.

PMID- 11994880
TI  - Complications of coarctation repair.
AB  - Surgery's role in the treatment of coarctation has been established, and the
      benefit to life expectancy and quality of life is undeniable. Three postaortic
      coarctation repair complications are discussed, with review of existing
      literature: recurrent or residual aortic coarctation, postrepair aneurysm
      formation, and spinal cord ischemia. Incidence, potential causative factors, and
      outcome of surgical or transcatheter treatment for recurrent and residual aortic
      coarctation are reviewed. A literature review of postrepair aneurysm formation
      focuses on etiologic factors such as use of patch aortoplasty repair techniques,
      aortic arch hypoplasia, congenital abnormality of the aortic wall, and persistent
      hypertension after repair. The spectrum, onset, incidence, and potential risk
      factors for postcoarctation repair spinal cord ischemia are reviewed. Use of
      adenosine receptor agonists to achieve a state of ischemic resistance is under
      investigation to address this potential hazard of coarctation repair.
      Complications after surgery do occur in certain subsets of patients, but the risk
      of subsequent intervention is still lower than the hazards associated with the
      natural course of the defect.

PMID- 11994881
TI  - Neonatal truncus arteriosus repair: surgical techniques and clinical management.
AB  - Truncus arteriosus is now ideally repaired in the neonatal period with low
      morbidity and mortality. Published reports have documented mortality rates in the
      range of 4% to 5% with mean age at repair as low as 11 days. The physiologic
      basis for improved outcomes with earlier repair is the avoidance of damaging
      sequelae of pulmonary overcirculation and heart failure. Data show that baseline
      mean pulmonary artery pressure is lower in infants undergoing earlier repair.
      Improved operative outcomes also have been achieved with aggressive truncal valve
      repair versus replacement in the presence of truncal valve dysfunction, right
      ventricular outflow tract reconstructive techniques that are patient anatomy
      specific, and use of regional perfusion techniques for repair of associated
      interrupted aortic arch. In addition, a heightened awareness of anomalies of
      coronary artery ostial location, number, angle of takeoff, and degree of patency
      can result in avoidance of inadvertent injury to the artery and associated
      myocardial insult.

PMID- 11994882
TI  - Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo
      controlled study.
AB  - OBJECTIVE: To determine whether aromatherapy with lavender oil is effective in
      the treatment of agitated behaviour in patients with severe dementia. DESIGN: A
      placebo controlled trial with blinded observer rater. SETTING: A long-stay
      psychogeriatric ward. PATIENTS: Fifteen patients meeting ICD-10 diagnostic
      criteria for severe dementia and suffering from agitated behaviour defined as a
      minimum score of three points on the Pittsburgh Agitation Scale (PAS).
      INTERVENTION: A 2% lavender oil aromatherapy stream was administered on the ward
      for a two hour period alternated with placebo (water) every other day for a total
      of ten treatment sessions. ASSESSMENTS: For each subject 10 total PAS scores were
      obtained. Five during treatment and five during placebo periods. RESULTS: Nine
      patients (60%) showed an improvement, five (33%) showed no change and one patient
      (7%) showed a worsening of agitated behaviour during aromatherapy compared with
      placebo. A comparison of the group median PAS scores during aromatherapy showed a
      significant improvement in agitated behaviour during aromatherapy compared with
      placebo (median PAS scores 3 c.f. 4; Wilcoxon Signed-Ranks test p = 0.016 (one
      tailed)). CONCLUSIONS: Lavender oil administered in an aroma stream shows modest
      efficacy in the treatment of agitated behaviour in patients with severe dementia.

PMID- 11994883
TI  - Does the presence of anxiety affect the validity of a screening test for
      depression in the elderly?
AB  - INTRODUCTION: Depression in the elderly is frequently detected by screening
      instruments and often accompanied by anxiety. We set out to study if anxiety will
      affect the ability to detect depression by a screening instrument. OBJECTIVE: To
      validate the short Zung depression rating scale in Israeli elderly and to study
      the affect of anxiety on its validity. DESIGN: The short Zung was validated
      against a psychiatric evaluation, in a geriatric inpatient and outpatient
      service. The overall validity was determined, as well as for subgroups of
      sufferers and non-sufferers of anxiety. SETTING: An urban geriatric service in
      Israel. PATIENTS: 150 medical inpatients and outpatients, aged 70 years and
      older. MEASURES: Psychiatric evaluation of modified Anxiety Disorders Interview
      Schedule for DSM-IV as criterion standard for anxiety and depression and short
      Zung instrument for depression. RESULTS: By criterion validity, 60% suffered from
      depression. The overall validity of the short Zung was high (sensitivity 71.1%,
      specificity 88.3%, PPV 90.1%, NPV 67.1%). The validity for those not suffering
      from anxiety was good (sensitivity 71.1%, specificity 90.2%, PPV 84.4%, NPV
      80.7%). In those with anxiety, sensitivity, specificity and PPV were high (71.2%,
      77.8%, 94.9% respectively), although the specificity was less than in non
      suffers. However major difference was in the NPV rate being much lower (31.8%).
      CONCLUSION: The short Zung, an easily administered instrument for detecting
      depression, is also valid in the Israeli elderly. However, anxiety limits the
      usefulness of this instrument in correctly ruling out depression. The clinician
      must be aware, therefore, that those suffering from anxiety may score negatively
      for depression on a screening instrument, such as the short Zung.

PMID- 11994884
TI  - Care management, dementia care and specialist mental health services: an
      evaluation.
AB  - OBJECTIVE: To evaluate a model of intensive case management for people with
      dementia based in a community-based mental health service for older people.
      METHOD: Quasi-experimental design. Individuals in one community team setting
      received case management and were compared with those in a similar team without
      such a service. Forty-three matched pairs were identified. Eligible older people
      and their carers were interviewed at uptake and again at 6 and 12 months.
      RESULTS: The impact of the scheme upon placement occurred in the second year at
      the end of which 51% of the experimental group remained at home compared with 33%
      of the comparison group. For the experimental group significant improvements in
      the social contacts of older people were noted; a decrease in the stress of their
      carers was observed, together with a reduction in their input to the care of the
      client; and there were significant improvements on ratings of overall need
      reduction, aspects of daily living and level of risk. Differences between the two
      groups based on service receipt showed higher costs for the experimental group.
      DISCUSSION: The benefits to older people and their carers confirms previous
      findings that the most effective case management interventions are those targeted
      on a highly specific client group. Issues which influence the cost-effectiveness
      of intensive case management are discussed. The benefits of locating this service
      within a specialist mental health team are explored in the context of current
      initiatives to promote greater service integration between health and social
      services.

PMID- 11994885
TI  - Olanzapine associated weight gain, hyperglycemia and neuroleptic malignant
      syndrome: case report.
AB  - We describe here a case of olanzapine associated weight gain, hyperglycemia and
      neuroleptic malignant syndrome in a 64 year-old woman with a significant medical
      history. Eighteen weeks after initiating olanzapine, Mrs X lost glycemic control,
      exhibited signs and symptoms consistent with neuroleptic malignant syndrome and
      gained 8.9 kg. We suggest that utilization of olanzapine in the less medically
      stable geriatric patient be implemented with vigilant monitoring for such
      complications mentioned above.

PMID- 11994886
TI  - Gait performance in dementia: the effects of a 6-week resistance training program
      in an adult day-care setting.
AB  - BACKGROUND: Age-related declines in balance and muscle power are largely
      responsible for the changes in the various components of gait performance among
      elderly people. But these can often be remedied with strength training. People
      with cognitive impairment frequently demonstrate impaired gait, putting them at
      increased risks for falls and serious injury. OBJECTIVES: This paper reports on
      the effects of a six-week pilot study of moderate intensity strength training on
      the gait of elderly individuals with dementia who attend a day-care center.
      METHODS: Twenty-six adults (23 female, three male), age = 79.2 +/- 6.6 years,
      completed the study. Each subject completed a baseline assessment of lower
      extremity strength and gait. Gait was evaluated using free- and fast-gait speed
      over a 6-meter course, the Tinetti-Gait Assessment scale, the 'Timed-Up-and-Go',
      and the Gait Assessment Rating Scale (GARS). The intervention consisted of
      moderate-intensity progressive resistance lower extremity exercise using
      Theraband, for two to three sessions per week over the six weeks. Post
      intervention assessment of strength and gait was repeated at the completion of
      the sixth week. Multiple paired t-tests were calculated for each outcome measure.
      RESULTS: The baseline assessment of gait suggests a high degree of frailty and
      risk for falls in the sample. Although post-intervention scores reflected
      improvement on all gait measures, the only statistically significant change
      observed was in fast-gait time. CONCLUSION: A six-week resistance training
      program proved to be of insufficient duration, intensity or specificity to
      produce significant change in gait outcome measures, with the exception of fast
      speed gait.

PMID- 11994887
TI  - Physical disorders and causes of death in relatives of Alzheimer's disease
      patients.
AB  - BACKGROUND: Genetic risk factors are important in Alzheimer's disease (AD). These
      risk factors might also predispose for other disorders. This might lead to a
      familial coaggregation of AD and other disorders, e.g. Down's syndrome or
      Parkinson's disease. In the present study the risk of physical disorders in
      relatives of AD patients, of depressed patients and of control subjects were
      compared. METHODS: Family history and, if possible, interview information on
      physical disorders and causes of death in relatives of 146 patients with AD, 168
      patients with major depression (MD) and 136 controls was collected. Statistical
      comparisons were performed using chi-square tests and, if necessary, logistic
      regression analysis accounting for age, gender and interview status. RESULTS: In
      contrast to our hypotheses, there was no increased risk of cerebrovascular
      disease, Down's syndrome, haematological malignancies or Parkinson's disease in
      relatives of AD patients compared with relatives of patients with MD and of
      controls. The explorative analysis revealed that congenital malformations, i.e.
      malformations of the heart or of the extremities, were slightly increased in
      relatives of AD patients. Relatives of patients with AD or MD were at increased
      risk of dying as a result of accidents, in most cases falls in advanced age, and
      relatives of patients with MD were at slightly increased risk of dying from
      gastroenterologic diseases, in most cases complications of peptic ulcers.
      CONCLUSION: The results do not support a major overlap between the genetic risk
      of AD and the genetic risk of cerebrovascular disease, Down's syndrome,
      haematological malignancies or Parkinson's disease. The finding of an increased
      risk of congenital malformations in relatives of AD patients needs further
      replication before it can be stated. The increased risk of dementia or depression
      with cognitive impairment in elderly relatives of patients with AD or MD
      increases the risk of accidents like falls. The genetic risk of depression in
      relatives of patients with MD could have a negative influence on the prognosis of
      peptic ulcera.

PMID- 11994888
TI  - A pilot, randomized, open-label trial assessing safety and pharmakokinetic
      parameters of co-administration of rivastigmine with risperidone in dementia
      patients with behavioral disturbances.
AB  - BACKGROUND: The majority of patients with Alzheimer's disease (AD) or vascular
      dementia display, in addition to cognitive impairment, various degrees of
      behavioral disturbances. As the use of cholinesterase inhibitors for the
      treatment of cognitive impairment in dementia becomes widespread, many of these
      patients will be treated concomitantly with cholinesterase inhibitors and with
      anti-psychotic drugs to ameliorate behavioral disturbances. Despite the
      widespread use of this combination in clinical practice, the safety and
      tolerability of such combination therapy has not been evaluated in controlled
      clinical trials. This pilot study examined the effects of addition of risperidone
      0.5-2 mg/day to patients on rivastigmine 3-12 mg/day, and vice versa. METHODS: 65
      patients suffering from AD, 10 from vascular dementia, and 15 from both were
      randomized to open label rivastigmine and risperidone, alone or in combination,
      for 20 weeks. Adverse events caused by co-administration were assessed. RESULTS:
      No clinically relevant adverse interactions were observed. CONCLUSIONS: These
      preliminary results indicate that rivastigmine and risperidone can be safely co
      administered. Confirmation of these results in large clinical trials studies is
      warranted.

PMID- 11994889
TI  - Ten-Point Clock Test: a correlation analysis with other neuropsychological tests
      in dementia.
AB  - BACKGROUND: Neuropsychology can be useful for differentiating patients with
      fronto-temporal dementia (FTD) from those with Alzheimer disease (AD) and those
      with Vascular Dementia (VaD). OBJECTIVES: The purpose of this study was twofold:
      to explore possible employment of the Ten-Point Clock Test in early
      identification of different types of cognitive distribution and to relate to its
      execution to other specific impairment, bound to the selected pathology. METHOD:
      We compared 30 patients with FLD, to a group of 30 probable-AD patients
      accordingly to the NINCDS-ADRDA criteria, and to a group of 30 probable VaD
      patients, according to the NINDS-AIREN criteria. RESULTS: AD group showed the
      worst results in Clock Drawing Test. On the contrary, FLD group did produce the
      worst performances in Proverb Interpretation Tasks. VaD worst performance was
      that of phonological fluency. Our data seem to demonstrate that in mild dementia,
      stated by the MMSE score (around 22) and confirmed by the data derived from the
      other neuropsychological evaluation, the Clock Drawing Test is quite sensitive to
      detect cognitive impairment, even if of different origins. CONCLUSIONS: Ten-Point
      Clock Test is a strong tool, in order to identify early forms of Alzheimer, and
      to help differential diagnosis when frontal or vascular dementia have been taken
      into account. More data will be necessary to give to this speculative
      interpretation, a neuroimaging and neuroanatomical support. However, this report
      may encourage the wider use of this parametric test, easily applicable and well
      accepted by the population in order to implement data concerning cognitive
      disruption.

PMID- 11994890
TI  - An examination of the attitudes and practice of general practitioners in the
      diagnosis and treatment of depression in older people.
AB  - BACKGROUND: Most depression in older people is managed in primary care settings
      but can be difficult to diagnose and is often under-treated. This study examined
      the attitudes and practice of general practitioners in the treatment of late-life
      depression using antidepressant medication. METHOD: Three hundred and thirty
      general practitioners in 116 general practices within the Nottingham Health
      Authority were surveyed. Their responses to a series of attitude statements and
      clinical vignettes regarding antidepressant prescribing were assessed. RESULTS:
      Analysis of vignettes showed newer antidepressants to be prescribed much more
      frequently than older antidepressants, with a substantial increase in the use of
      SSRIs compared to the results of previous research. Older general practitioners
      and those who had been in practice for longer were more likely to prescribe
      tricyclic antidepressants. They were also more likely to identify a need for
      extra training in treating old age depression, as were those GPs without previous
      psychiatric training. However, most GPs were confident in treating depression in
      the elderly although younger GPs were the most confident. CONCLUSIONS: Selective
      Serotonin Re-Uptake Inhibitors are the preferred drugs in treating certain
      problematic cases of late-life depression. These results suggest there may be a
      greater propensity for GPs to prescribe SSRIs although further research is needed
      to clarify whether this finding can be generalised beyond this study. Most
      general practitioners felt confident in treating late-life depression, but older
      doctors, those who had been practising for longer and those without previous
      psychiatric training, may benefit most from further training.

PMID- 11994891
TI  - Ageing and the nigrostriatal dopaminergic system.
AB  - BACKGROUND: Brain dopamine has been the focus of numerous studies owing to its
      crucial role in motor function and in neurological and psychiatric disease
      processes. Whilst early work relied on postmortem data, functional imaging has
      allowed a more sophisticated approach to the quantification of receptor density,
      affinity and functional capacity. This review aims to summarise changes in the
      nigrostriatal dopaminergic system which accompany normal ageing. METHODS: A
      literature search focussed on postmortem and neuroimaging studies of normal
      ageing within the nigrostriatal dopaminergic tract. The functional significance
      of age-related effects was also considered. RESULTS: There are significant
      reductions in pre- and post-synaptic markers of brain dopamine activity during
      normal ageing: However the rate of decline (linear or exponential), the effects
      of gender and heterogeneity and the mechanisms by which these changes occur
      remain undetermined. Limited data suggest there is a significant association
      between postsynaptic receptor density and specific aspects of motor and cognitive
      function. CONCLUSION: The identification of strategies to improve dopaminergic
      transmission may delay the onset of motor and cognitive deficits associated with
      normal ageing. In order to develop effective preventative strategies, the
      causative mechanisms underlying age-related changes and the interaction between
      synaptic structure and function need to be more clearly elucidated.

PMID- 11994892
TI  - Decreased cutaneous vasodilatation to isometric handgrip exercise in Alzheimer's
      disease.
AB  - BACKGROUND: Cutaneous active vasodilatation is a cholinergic nerve mediated
      function of the sympathetic nervous system and the disturbed function of
      cholinergic neurotransmission is known as a prominent feature of Alzheimer's
      disease (AD). METHODS: To assess this relationship, skin blood flow (SkBF) and
      other haemodynamic parameters were determined by a simple vasodilatory test,
      isometric handgrip exercise (IHG), in 22 late-onset sporadic type AD and 20 aged
      control persons (AC). RESULTS: Significantly higher cutaneous vascular resistance
      and decreased SkBF were found after the stimulus in the AD group. A smaller
      reduction (p < 0.03) of R wave intervals on the electrocardiogram was observed in
      the AD group compared to the AC one. After IHG, change in systolic blood pressure
      was less in the AD (p < 0.01) than in the AC group. CONCLUSION: Our results
      suggest that autonomic dysfunction affecting active vasodilator sympathetic, as
      well as parasympathetic functions is present in AD.

PMID- 11994893
TI  - Geriatric Depression Scale Scores in a representative sample of 14 545 people
      aged 75 and over in the United Kingdom: results from the MRC Trial of Assessment
      and Management of Older People in the Community.
AB  - BACKGROUND: The 15-item Geriatric Depression Scale (GDS-15) is recommended for
      screening older people, but there are no large epidemiological studies using this
      instrument in the UK. We describe the age and sex distribution of GDS-15 scores
      in the largest ever UK sample of people aged 75 and over. METHOD: We used cross
      sectional data from the MRC Trial of the Assessment and Management of Older
      People in the Community. The GDS-15 was offered to a representative sample of UK
      people aged 75 and over. Proportions of people attaining thresholds on the GDS-15
      were calculated by age group and sex. Crude Odds ratios (ORs) for the effect of
      age and sex were calculated and the sex/age adjusted ORs estimated using logistic
      regression for surveys, at three GDS-15 thresholds. RESULTS: Of 21 241 (71.2%;
      95% Confidence intervals (CI): 67.9-74.3) eligible people, 15 126 received the
      assessment including the GDS-15. Of these, 14 545 (96.2%; 94.7-97.2) completed >
      or =13 GDS-15 answers and were included in the study. Scores showed a marked
      right skew, with a median of 2 (interquartile range: 1-3; range: 0-14). 34.6%
      (95% CI: 32.1-37.3) people scored > or =3, 8.0% (6.9-9.2) scored > or =6 and 3.1%
      (2.5-3.7) scored > or =8. Women were significantly more likely to score above all
      three thresholds than men, as were older participants. CONCLUSIONS: Depression
      may be common in later life. The data provide a national picture of the numbers
      of older people who will score positively for depression in health screens which
      include the GDS-15, as recommended by the Royal College of General Practitioners.

PMID- 11994894
TI  - Negative symptoms, depression and Alzheimer's disease.
AB  - OBJECTIVES: To apply the negative symptoms (NS) concept used in schizophrenia to
      patients with AD, to compare the results with the frontal lobe perfusion in ethyl
      cysteinate dimmer (ECD) single-photon emission computed tomography (SPECT) and
      with the apolipoprotein E genotype. METHOD: 32 patients with a diagnosis of
      probable AD were assessed by the Positive and Negative Symptoms Scale (PANSS-N),
      the Montgomery and Asberg Depression Scale (MADRS), the NeuroPsychiatric
      Inventory (NPI), and the Mini-Mental Status Examination (MMSE). Each patient
      underwent ECD SPECT and APO E genotyping. PANSS-N, MADRS, NPI, and MMSE were
      administered to 19 normal elderly control subjects. RESULTS: The mean PANSS-N
      score for AD patients (20.56, SD: 8, range: 7-40) was significantly higher (p <
      0.001) than that of controls (7, SD: 0). MADRS scores were not significantly
      different (p = 0.75) between AD patients (9.03, SD: 6.14, range: 0-25) and
      controls (6.2, SD: 3.61, range: 1-15). The NPI apathy score (0-12) was correlated
      with PANSS-N (p < 0.001). Correlation between prominent frontal hypoperfusion
      (six cases) and NS was at the limit of significance. No relation was found
      between epsilon E4 and NS. CONCLUSION: This consideration is important in
      distinguishing between depression and AD.

PMID- 11994895
TI  - How to define treatment success using cholinesterase inhibitors.

PMID- 11994896
TI  - Effects of selegiline on fronto-temporal dementia: a neuropsychological
      evaluation.

PMID- 11994897
TI  - Current awareness in geriatric psychiatry.

PMID- 11994899
TI  - Considerations for treating dyslipidemia in special diabetic populations.
AB  - This is a review of the problem of dyslipidemia and cardiovascular disease (CVD)
      in special diabetic populations. Clearly all patients with diabetes are at
      increased risk for CVD compared to non-diabetic populations. But within the
      subset that is patients with diabetes there are individuals who are particularly
      vulnerable. These groups include women, who are often overlooked and undertreated
      for their cardiovascular risk. Additionally, it includes those with fewer
      resources, many from minority populations, who are at very high risk for poor
      preventive care and serious cardiovascular morbidity. This review details the
      risk for CVD in a variety of different diabetic high-risk groups. It then
      discusses treatment options and approaches that should be employed in these
      populations.

PMID- 11994900
TI  - Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal
      consequences.
AB  - There is strong evidence that the avoidance of hyperglycemia is essential
      inoptimizing pregnancy outcome in type 1 diabetes. The price to pay is a striking
      increase in severe hypoglycemia (SH), defined as episodes requiring help from
      another person. During type 1 diabetic pregnancy, occurrence rates of SH up to 15
      times higher as in the intensively treated group of the Diabetes Control and
      Complications Trial (DCCT) are reported. Blood glucose (BG) treatment targets
      differ considerably between clinics; some authors advocate lower limits as low as
      3.3 mmol/l. Improved glycemic control and/or recurrent hypoglycemia (i.e. BG <3.9
      mmol/l) may result in impairment of glucose counterregulatory responses. Also,
      glucose counterregulation may be altered by pregnancy itself. Short-acting
      insulin analogs may help reduce hypoglycemia with preservation of good glycemic
      control, but their use during pregnancy has yet to be proven safe.Several
      clinical studies did not establish an association between maternal hypoglycemia
      and diabetic embryopathy. However, animal studies clearly indicate that
      hypoglycemia is potentially teratogenic during organogenesis. Increased rates of
      macrosomia continue to be observed despite near normal HbA(1c) levels. This may,
      at least in part, be the result of rebound hyperglycemia elicited by
      hypoglycemia. Exposure to hypoglycemia in utero may have long-term effects on
      offspring including neuropsychological defects. It is yet unclear to what extent
      the benefits of tight glycemic control balance with the increased risk of
      (severe) hypoglycemia during type 1 diabetic pregnancy. Efforts must be made to
      avoid low BG, i.e. <3.9 mmol/l, when tightening glycemic control.

PMID- 11994901
TI  - The search for type 2 diabetes susceptibility genes using whole-genome scans: an
      epidemiologist's perspective.
AB  - Most whole-genome scan studies of type 2 diabetes have ascertained families on
      affected sibpairs. Although assuring enrollment of multiplex families, this
      strategy may lead to the enrollment of unrepresentative families, particularly in
      low-risk populations where relatively few diabetics have an affected sibling. In
      high-risk populations such as Hispanics and Native Americans, population-based
      ascertainment is often possible, since the high frequency of the disease favors
      enrollment of multiplex families even when they are not specifically sought. The
      results of the first generation of genome scan studies caused concern because of
      a perceived lack of reproducibility. More recently, however, a number of
      replications have emerged, specifically on chromosomes 1q, 2q, 3q, 9p, 10q, and
      11q. The MODY 1 and 3 regions on chromosome 12q and 20q have also been replicated
      in multiple studies. The clinical features of diabetes in these latter families,
      however, suggest the common form of type 2 diabetes, rather than maturity-onset
      diabetes of the young (MODY). Also, diabetes in these families does not appear to
      be caused by the classical MODY mutations. Interestingly, functional variants of
      the MODY 4 gene (insulin promoter factor-1) have been associated with both MODY
      and the common form of type 2 diabetes. Currently available linkage studies
      implicate relatively broad chromosomal regions, and the challenge of narrowing
      these regions to facilitate gene discovery remains formidable. The linkages that
      have been replicated thus far provide good starting points to search for
      functional variants in type 2 diabetes susceptibility genes.

PMID- 11994902
TI  - Thiazolidinediones for the prevention of diabetes in the non-obese diabetic (NOD)
      mouse: implications for human type 1 diabetes.
AB  - BACKGROUND: Thiazolidinediones (TZDs) are a recently introduced generation of
      drugs acting as receptor agonists to reduce insulin resistance and used currently
      in combination with other hypoglycaemic agents for the treatment of type 2
      diabetes. In addition, TZDs possess anti-inflammatory properties that make them
      of interest for reducing the T-cell inflammation occurring in the islets in type
      1 diabetes. METHODS: The action of TZD treatment on diabetes incidence in the non
      obese diabetic (NOD) mouse was studied by investigating the effect of
      rosiglitazone (RGL) (400 mg/kg body weight by gavage) from 3 weeks of age (soon
      after weaning) onwards and comparing its effect to that of troglitazone (TGL)
      given by the same route. RESULTS: We found that RGL and TGL both significantly
      reduced diabetes incidence by >50% in the NOD mouse compared to litter-matched
      control NOD mice (p<0.05 and p<0.01, respectively). However, the withdrawal of
      TGL from the market due to hepatotoxicity led us to re-analyse our data for toxic
      liver effects. We found that TGL was more toxic to mice than RGL (causing ten
      deaths as compared with one death). CONCLUSION: RGL reduces diabetes incidence in
      the NOD mouse model of type 1 diabetes. This may be an effect resulting from its
      action as on inhibitor of pro-inflammatory genes such as cytokines and metabolic
      proteases. Its use may be considered for trials designed to protect beta-cell
      function in humans, especially in patients with latent autoimmune diabetes of
      adults (LADA) and also for disease prevention.

PMID- 11994903
TI  - Role of amylin in insulin secretion and action in humans: antagonist studies
      across the spectrum of insulin sensitivity.
AB  - BACKGROUND: Amylin is a peptide co-secreted with insulin by pancreatic beta
      cells. A role for amylin in the pathogenesis of type 2 diabetes mellitus (DM2)
      has been suggested by in vitro and in vivo studies indicating an effect of amylin
      to cause insulin resistance and/or inhibit insulin secretion. METHODS: We have
      determined the effect of endogenous amylin on insulin secretion and insulin
      action in humans by performing 4-h hyperglycemic clamps during infusion of
      placebo or a specific amylin receptor antagonist (ARA) in paired, double-blinded,
      crossover studies. We studied nine healthy lean, ten healthy obese (BMI>27) and
      ten obesity-matched DM2 subjects. RESULTS: Infusion of ARA alone had no effect on
      basal insulin, glucose or glucose turnover in any group. Under combined
      hyperglycemia and ARA infusion, lean subjects displayed a 32% augmentation in
      insulin levels [AUC 33,565+/-3556 (placebo) to 44,562+/-1379 (ARA) pmol/l/min,
      p<0.01]. The concomitant increase in glucose disposal rate (GDR) was
      proportionate, indicating no change in insulin sensitivity (ISI 27.7+/-2.7 vs
      27.3+/-2.1, p=NS). In obese subjects, basal insulin and the rise in insulin
      during the clamp were greater (AUC I 44% increase from 82,054+/-15 407 to
      117,922+/-27,085, p<0.01), and also accompanied by a proportionate rise in GDR
      reflecting an unchanged insulin sensitivity (ISI 12.1+/-2.9 vs 10.8+/-3.0, p=NS).
      In lean and obese subjects, the C-peptide response to hyperglycemia was also
      augmented by ARA (p=0.007). No effect of ARA on insulin secretion or action was
      observed in diabetic subjects. CONCLUSIONS: The present data are consistent with
      an effect of endogenous amylin on the beta-cell to modulate and/or restrain
      insulin secretion, and indicate that endogenous amylin does not affect insulin
      action. These observations provide the first human evidence that amylin plays a
      role in the modulation of insulin secretion.

PMID- 11994904
TI  - Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2
      diabetes.
AB  - BACKGROUND: Type 2 diabetes is a growing problem in Mexico. The present study was
      undertaken to evaluate the efficacy and safety of rosiglitazone 2 mg or 4 mg
      twice daily (bd) in combination with metformin 2.5 g/day in Mexican patients
      whose type 2 diabetes was inadequately controlled with metformin alone. METHODS:
      This randomized, double-blind, placebo-controlled study was conducted at four
      centers in Mexico. A total of 116 patients were randomized to metformin 2.5 g/day
      plus placebo (n=39), metformin 2.5 g/day plus rosiglitazone 2 mg bd (n=37), or
      metformin 2.5 g/day plus rosiglitazone 4 mg bd (n=40) for 26 weeks. RESULTS: Mean
      hemoglobin A(1c) (HbA(1c)) levels decreased significantly from baseline to Week
      26 in the rosiglitazone 2 mg bd (-0.7%; p=0.0052) and 4 mg bd (-1.2%; p=0.0008)
      groups, but increased in the placebo group (+0.3%; p=0.2651). Mean fasting plasma
      glucose and fructosamine levels also improved significantly with metformin plus
      rosiglitazone therapy in a dose-ordered manner compared with placebo (p<or=0.0019
      and p=0.0006, respectively). C-peptide and immunoreactive insulin levels were
      decreased from baseline in both rosiglitazone groups. Although mean increases in
      total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density
      lipoprotein (HDL)-cholesterol were observed in the rosiglitazone groups, the
      total cholesterol:HDL-cholesterol ratio remained unchanged. The proportion of
      patients with one or more adverse events was similar across all three groups.
      There were no cases of hepatotoxicity. CONCLUSION: Addition of rosiglitazone 2 mg
      bd and 4 mg bd to metformin therapy improved glycemic control in Mexican patients
      whose type 2 diabetes was inadequately controlled by metformin alone.
      Furthermore, the combination of rosiglitazone plus metformin was well tolerated.

PMID- 11994905
TI  - Incidence and onset features of diabetes in African-American and Latino children
      in Chicago, 1985-1994.
AB  - AIMS: The study aimed to describe the epidemiology of diabetes in minority
      children residing in Chicago, IL, USA, and to compare the demographic and
      clinical characteristics of those with type 1 to those with youth-onset type 2
      diabetes. METHODS: Medical records were obtained on 735 insulin-treated African
      American and Latino children aged 0-17 years at onset, and diagnosed between 1985
      and 1994; 195 of the children were interviewed. Subjects were presumed to have
      type 2 diabetes if they fitted specific criteria. Univariate and multivariate
      analyses were conducted and Poisson regression was used to analyze time trends.
      RESULTS: Ten-year average annual incidence of childhood diabetes for African
      Americans [15.2/10(5), 95% confidence interval (CI): 13.5, 17.0] was
      significantly higher than for Latinos (10.7/10(5), 95% CI: 9.1, 12.6). The
      average annual incidence was 10.3/10(5) population for type 1 and 3.2/10(5) for
      those with presumed type 2 diabetes. Most patients (99.6% of type 1, 94.1% of
      type 2) exhibited more than one of the classic onset symptoms of type 1 diabetes.
      Mean age at diagnosis was older, 13.1 versus 10.5 years, and there were more
      females, 62.4%, versus 49.8%, among the type 2 patients; ethnicity was not an
      important distinguishing factor. CONCLUSION: The risk of childhood diabetes
      increased among African-Americans and Latinos between 1985 and 1994, driven by an
      increase in children with type 2 diabetes. This is likely related both to an
      increase in risk factors, i.e. obesity, and to changes in diagnostic practice.

PMID- 11994906
TI  - No role of calcium- and ATP-dependent potassium channels in insulin-induced
      vasodilation in humans in vivo.
AB  - The mechanism of insulin-induced vasodilation has not been completely clarified,
      but could be important in future treatment strategies of insulin resistance.
      Recently, a role for calcium-dependent and ATP-dependent potassium (K(Ca) and
      K(ATP)) channels in insulin-induced vasodilation has been demonstrated in in
      vitro studies. A role for these channels has never been confirmed in humans in
      vivo. Therefore, we investigated the role of these channels in insulin-induced
      vasodilation in humans in vivo. A hyperinsulinemic euglycemic clamp was combined
      with intra-arterial infusion of placebo, tetraethylammonium (blocker of K(Ca)
      channels) or glibenclamide (blocker of K(ATP) channels) in three groups of 12
      healthy volunteers. Bilateral forearm blood flow was measured with venous
      occlusion plethysmography. Systemic hyperinsulinemia induced a 20+/-9%
      vasodilation (p=0.001). Neither tetraethylammonium nor glibenclamide reduced this
      vasodilation as compared to placebo. According to the results of the present
      study, insulin-induced vasodilation seems not to be mediated by the opening of
      K(Ca) and K(ATP) channels in humans in vivo.

PMID- 11994907
TI  - Higher fasting insulin but lower fasting C-peptide levels in African Americans in
      the US population.
AB  - BACKGROUND: Fasting serum insulin and fasting serum C-peptide are risk factors
      for developing type 2 diabetes. Because of the higher incidence of type 2
      diabetes in African Americans and Hispanic Americans, it is likely that these
      groups may differ from non-Hispanic whites in their levels of insulin and C
      peptide. METHODS: We analyzed data from a nationally representative sample of
      adults in the US population for whom sociodemographic, clinical, and laboratory
      information were obtained. The data were used to describe distributions of
      fasting insulin and fasting C-peptide in non-Hispanic white, non-Hispanic black,
      and Mexican American men and women aged >or=20 years without a medical history of
      diabetes. RESULTS: Among men, Mexican Americans had higher insulin values than
      non-Hispanic whites and blacks. Among women, both Mexican Americans and blacks
      had higher insulin values than whites. For C-peptide, differences by sex and race
      ethnicity paralleled those seen for fasting insulin with the exception that black
      men had significantly lower C-peptide values than whites and Mexican Americans.
      After adjustment for age, fasting plasma glucose (FPG), body mass index (BMI),
      and waist-to-hip ratio (WHR), the higher levels for insulin in blacks and Mexican
      Americans remained; both black men and women had significantly lower C-peptide
      values than whites and Mexican Americans. The molar ratio of fasting C-peptide to
      fasting insulin was similar for men and women in each race-ethnic group. However,
      blacks had substantially lower ratios than whites and Mexican Americans.
      CONCLUSIONS: We found wide variations in fasting insulin and fasting C-peptide
      levels by race and ethnicity in US adults that were not explained by confounding
      factors, primarily measures of obesity. Most notably, the higher fasting insulin
      and lower fasting C-peptide levels in blacks implies that there is a derangement
      in insulin clearance and an impairment in beta-cell function in blacks compared
      with whites and Mexican Americans.

PMID- 11994908
TI  - Metformin decreases platelet superoxide anion production in diabetic patients.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus are usually treated with oral
      antidiabetic agents but it is still not known whether these drugs have
      antioxidant effects in humans. METHODS: We studied 60 patients with type 2
      diabetes mellitus, divided into three groups on the basis of hypoglycaemic
      treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All
      patients were followed for at least 1 year. The three subgroups had similar
      clinical characteristics. Twenty healthy subjects, of comparable sex and age,
      were enrolled as controls. In each subject, platelet production of superoxide
      anion (O(2)(-)) elicited by collagen, was determined by lucigenin assay. RESULTS:
      Patients with diabetes had higher platelet O(2)(-) production than controls; no
      correlation was observed between blood glucose and platelet O(2)(-) production.
      Group A patients had platelet O(2)(-) production similar to that of healthy
      subjects but lower than Group B and Group C patients. CONCLUSION: The present
      findings suggest an in vivo antioxidant activity of metformin and warrant
      prospective studies to further explore this hypothesis.

PMID- 11994909
TI  - Current literature in diabetes.

PMID- 11994927
TI  - The cost of behavioral and psychological symptoms of dementia (BPSD) in community
      dwelling Alzheimer's disease patients.
AB  - INTRODUCTION: Behavioral and psychological symptoms of dementia (BPSD) are highly
      prevalent in Alzheimer's disease (AD) patients. They are a source of distress for
      the caregivers and one of the main reasons for nursing home placement, which is
      the major component of the cost of Alzheimer's disease. The aim of the present
      study was to assess the direct and indirect cost related to the care of BPSD
      within a prospective study examining the overall cost of AD in Israel. METHODS:
      Seventy-one community dwelling AD patients were interviewed. Interviews covered
      information about the number of caregivers' hours invested in caring for the
      patient and amount of expenditure such as in-house paid help and payments for day
      care. Effort devoted to BPSD was defined as the number of hours spent by primary
      and secondary caregivers in a typical week dealing with BPSD (managing
      aggression, pacing, attempts to leave the house under inappropriate
      circumstances, or comforting a hallucinating, depressed or anxious patient).
      RESULTS: The annual indirect cost for management of BPSD in an AD patient was
      approximately 2665 dollars -over 25% of the total annual indirect cost of care
      ($10 520). The annual direct cost of BPSD of an AD patient was approximately 1450
      dollars -over 35% of the total annual direct cost of care (3900 dollars).
      CONCLUSIONS: Approximately 30% (4115 dollars) of the total annual cost of AD
      (14420 dollars) is invested in the direct management of BPSD. Given the
      importance of BPSD as one of the main components of the cost of AD, future cost
      studies should be designed to measure the cost of specific components of BPSD and
      verify which are the most costly aspects of the disease. Despite the considerable
      methodological difficulties in disentangling the costs of the specific symptoms
      of AD, cost effectiveness studies of different interventions should be conducted
      in order to determine the optimal intervention with relation to cost.

PMID- 11994928
TI  - Prevalence and correlates of late-life depression compared between urban and
      rural populations in Korea.
AB  - BACKGROUND: The aetiology of late-life depression has received relatively little
      research in developing countries. Urban and rural populations have rarely been
      sampled in the same study. OBJECTIVES: To investigate demographic factors
      associated with depression and depressive symptoms in an urban and rural sample
      of older Korean people. METHODS: A community survey of residents aged 65 or over
      was conducted in an urban and a rural area within Kwangju, South Korea. The
      Korean Form of the Geriatric Depression Scale (KGDS) was administered.
      Associations with demographic, socio-economic factors and cognitive function
      (MMSE) were investigated for depression categorised according to a previously
      validated cut-off. RESULTS: The sample comprised 485 urban-dwelling and 649 rural
      dwelling participants. No difference was found between urban and rural samples
      for prevalence rates of depression. However associations with independent
      variables varied between the areas. In the urban sample, increased age, low
      education, manual occupation and current rented accommodation were independently
      associated with depression. Only low education was associated with depression in
      the rural sample. The interaction with sample area was strongest for age (p <
      0.01) and persisted after further adjustment for cognitive function. CONCLUSIONS:
      Adverse socio-economic status was strongly associated with depression and
      appeared to operate across the life-course. While no evidence was found for urban
      rural differences in prevalence rates of depression, factors associated with
      depression differed between these populations.

PMID- 11994929
TI  - Trends in suicide from drug overdose in the elderly in England and Wales, 1993
      1999.
AB  - BACKGROUND: Drug overdose is a common method of suicide in the elderly. Hence, an
      understanding of current trends in epidemiology of these deaths is important when
      considering measures to decrease suicide rates. METHODS: Analysis of the Office
      for National Statistics (ONS) database of deaths from overdose and poisoning.
      Suicide and undetermined deaths from drug overdose between 1993-1999 in the over
      65 year olds were studied. Socio-demographic data from the four drug groups most
      commonly used in overdose were extracted, and age and sex specific mortality
      rates calculated. Enumeration districts were ranked into five quintiles based on
      their Carstairs scores, and death rates in each quintile for men and women
      calculated. RESULTS: There were 1864 deaths from drug overdose during the study
      period. Suicide and undetermined death rates from drug overdose remained stable
      between 1993-1999. Drugs most commonly used in overdose were (in order)
      paracetamol (and related compounds), benzodiazepines, antidepressants, and
      opiates. Women comprised 62% of deaths. Death rates increased with age, with
      highest rates in men over 75 (37.7 deaths per million). Benzodiazepines showed
      the most marked increase with age. Co-proxamol comprised 32% of deaths from
      paracetamol compounds, and 95% of antidepressant deaths were due to tricyclic
      antidepressants. There was no association in women between Carstairs area
      deprivation and suicide rates; in men rates were highest in the most deprived
      areas. CONCLUSION: Suicides in the over 65 year olds may be decreased by changes
      in prescription practice. Paracetamol, co-proxamol, tricyclic antidepressants and
      benzodiazepines should be prescribed with caution to the elderly with depression
      or at high risk of depression.

PMID- 11994930
TI  - Predictive factors of acute hospitalization in 134 patients with Alzheimer's
      disease: a one year prospective study.
AB  - OBJECTIVE: To evaluate the frequency of and determine predictive factors for
      acute hospitalization in a prospective study of patients with Alzheimer's disease
      (AD). DESIGN: A one year prospective study. PARTICIPANTS: 134 patients recruited
      from the memory clinic in Toulouse University Hospital, with AD diagnosed using
      the NINCDS-ADRDA criteria. MEASURES: A comprehensive geriatric and
      neuropsychological assessment was conducted 6 monthly. RESULTS: Among the 134
      patients included in this study, at one year follow up, 32 patients had at least
      one acute hospitalization. Patient-related variables predictive of acute
      hospitalization in the univariate analysis were: level of education, ADL-bathing,
      ADL-toileting, ADL-feeding, total ADL score, IADL A scale (daily upkeep), history
      of falls, and level of behavioural disorder as measured by the Cohen scale. In
      the multivariate regression model, two variables were associated with acute
      hospitalization: dependency for ADL-bathing [Odds Ratio (OR) = 5.65, 95%
      Confidence Intervals (CI): 2.3-14.4] and low level of education. CONCLUSION: The
      results of this study demonstrate that acute hospitalization is frequent in AD
      patients resulting in considerable cost implications. Interventions that support
      patients and their cares to manage their loss of ADL may be a practical approach
      to reducing the need for acute hospital admissions.

PMID- 11994931
TI  - Mental health in older adult recipients of primary care services: is depression
      the key issue? Identification, treatment and the general practitioner.
AB  - OBJECTIVES: Mental health services for older people in primary care are
      relatively underdeveloped. This study has sought to determine the nature and
      extent of mental health problems in older people presenting to primary care and
      to compare this with the detection and management of mental health problems by
      the primary health care team (PHCT). METHOD: Participants were patients aged 65
      years and above attending a representative inner city general practice. Screening
      tools included the General Health Questionnaire (GHQ-28), Hospital Anxiety and
      Depression Scale (HADS), Mini Mental State Examination (MMSE). The PHCT used a
      brief checklist to rate participants for the presence of mental health problems.
      Follow-up interviews using the Geriatric Mental State (GMSA), Cambridge
      Examination for Mental Disorders in the Elderly (CAMDEX)-cognitive subscale
      (CAMCOG), National Adult Reading Test (NART), were carried out. RESULTS: A high
      level of psychological morbidity was identified at screening (48.1%). There was a
      considerable degree of agreement between the HADS and GMSA, and the MMSE and GMSA
      at follow-up. Agreement rates between the PHCT and initial screening tools were
      low suggesting under-recognition of mental health problems at primary care level
      by the PHCT. Contributory factors included: short consultation times with a
      concentration on physical symptoms; few patients presenting explicitly with
      mental health problems; few decisions to treat or refer patients; and the general
      practitioners tended to monitor, or defer decisions. CONCLUSIONS: This study
      found lower levels of severe mental health problems, especially depression, than
      reported elsewhere, but higher prevalence of psychological distress. High levels
      of physical and mental health co-morbidity were found. These findings suggest
      that planning for primary care services needs to adopt a flexible assessment
      model. The development of effective, time-limited protocols and screening tools
      to assist the PHCT in improving their identification rates is recommended. This
      needs to be supported by the availability of appropriate treatments for the
      psychological distress.

PMID- 11994932
TI  - Measuring change in psychiatric symptoms using the Neuropsychiatric Inventory:
      Nursing Home version.
AB  - BACKGROUND: The Neuropsychiatric Inventory-Nursing Home version (NPI-NH) is a
      modified version of the Neuropsychiatric Inventory (NPI). Accurate interpretation
      of change in the symptom ratings on the NPI-NH, as with any measure, is a concern
      for both clinicians and researchers. The purpose of this article is to present
      data for the interpretation of reliable change in the NPI-NH scores for acute
      geriatric neuropsychiatry patients. METHOD: Fifty-two geriatric psychiatry
      inpatients were administered the NPI-NH twice, at a 72-hour interval. Standard
      errors of difference scores were used to calculate confidence intervals for each
      of the NPI-NH subscales and the total score. RESULTS: Based on the calculations
      described above, estimates of reliable change on the individual subscales ranged
      from plus or minus 1.29 points on the Euphoria/Elation subscale to 5.13 points on
      the Anxiety subscale. Statistically meaningful change on the Agitation and the
      Apathy subscales was established at 4.0 and 4.3 points, respectively. A change in
      the total score of plus or minus 22 points is required to exceed the possible
      range of measurement error, at a 0.80 confidence interval (CI). CONCLUSIONS:
      Overall, the results of this study indicate that the clinician evaluating elderly
      psychiatric inpatients should interpret a change in the total score of less than
      22 points with caution, because it may be due to measurement error.

PMID- 11994933
TI  - The prevalence and phenomenology of auditory hallucinations among elderly
      subjects attending an audiology clinic.
AB  - BACKGROUND: Studies of auditory hallucinations are scant. METHOD: To determine
      the prevalence and phenomenology of auditory hallucinations among elderly
      subjects with hearing impairment. OBJECTIVE: We surveyed 125 men and women aged
      65 years and over referred to the Audiology department of a university-affiliated
      primary acute-care hospital. RESULTS: The prevalence of auditory hallucinations
      was 32.8% (95% confidence interval (CI) 24.7-41.8). These hallucinations
      represented a spectrum of phenomenology from elementary personal impressions to
      complex percepts. The types of auditory hallucinations included humming or
      buzzing (35.9%), shushing (12.8%), beating or tapping (10.6%), ringing (7.7%),
      other individual sounds (15.4%), multiple sounds (12.6%), voices (2.5%) or music
      (2.5%). Subjects with any type of hallucination were younger and had poorer
      discrimination scores in the left ear and impaired binaural discrimination with
      lip-reading. Subjects with hallucinations that had more qualities of a true
      percept heard different types of sounds and had lower reflex thresholds and
      better air conduction in the right ear. CONCLUSION: Auditory hallucinations are
      frequent in elderly subjects with hearing impairment and seem to be associated
      with younger age and asymmetrical hearing impairment.

PMID- 11994934
TI  - Previous stroke but not vascular risk factors are associated with depression in a
      cognitively impaired older Korean population.
AB  - BACKGROUND: Depression is frequently associated with dementia and mild cognitive
      impairment. Cerebrovascular disease may be an important aetiological factor for
      depression in the context of cognitive impairment but has received little
      investigation in population-based research. OBJECTIVES: To investigate the
      association between vascular disease/risk and depression in an older Korean
      population with cognitive impairment. METHODS: The sample consisted of 341
      persons, drawn from a community study in Kwangju, South Korea, all aged 65 or
      over and with scores of 24 or below on the Korean version of the Mini-Mental
      State Examination. Depression (Hamilton Rating Scale for Depression), vascular
      disease/risk (interview, examination and blood tests), and disablement were
      ascertained. RESULTS: Previous stroke was associated with depression (Odds Ratio
      3.4, 95% Confidence Intervals 1.6-7.4). This association was weaker in the
      presence of more severe cognitive impairment and higher levels of dependency. No
      associations were found between depression and any other measures of vascular
      risk. CONCLUSIONS: In the absence of previous stroke, a role of vascular
      disease/risk was not supported in the aetiology late-life depression.

PMID- 11994935
TI  - Development and inter-rater reliability of a standardized verbal instruction
      manual for the Chinese Geriatric Depression Scale-short form.
AB  - The Geriatric Depression Scale (GDS) is a common screening tool for elderly
      depression in Hong Kong. This study aimed at (1) developing a standardized manual
      for the verbal administration and scoring of the GDS-SF, and (2) comparing the
      inter-rater reliability between the standardized and non-standardized verbal
      administration of GDS-SF. Two studies were reported. In Study 1, the process of
      developing the manual was described. In Study 2, we compared the inter-rater
      reliabilities of GDS-SF scores using the standardized verbal instructions and the
      traditional non-standardized administration. Results of Study 2 indicated that
      the standardized procedure in verbal administration and scoring improved the
      inter-rater reliabilities of GDS-SF.

PMID- 11994936
TI  - The prevalence, diagnosis and treatment of depression in dementia patients in
      chronic care facilities in the last six months of life.
AB  - OBJECTIVE: To assess the prevalence, diagnosis and treatment of depression among
      dementia patients and normal controls in chronic care facilities in the last six
      months of life. METHOD: We reviewed perimortal data concerning dementia severity,
      depressive symptoms and diagnoses, and medication use for 279 dementia patients
      and 24 normal controls brought to autopsy through an Alzheimer's Disease Resource
      Center. RESULTS: Major depression was highly prevalent among both dementia
      patients and normal controls in chronic care facilities in the last six months of
      life. This depression was under-diagnosed by physicians. Documentation of
      depressive symptoms by medical support staff has improved over time. However,
      physician diagnosis of depression has not improved. Recognition of depression was
      significantly lower for patients with severe dementia. Depression was under
      treated in both dementia patients and normal controls, although treatment rates
      may be increasing. Anxiolytics and hypnotics were often used in lieu of, or in
      addition to, antidepressant therapy. CONCLUSIONS: Major depression was highly
      prevalent in both dementia patients and normal controls, indicating that
      depression is an important issue for the elderly in the last six months of life
      irrespective of cognitive status. Under-diagnosis of depression may be an
      important clinical issue. As physician diagnosis of depression has not improved
      with time, further physician training and/or awareness initiatives may be
      warranted. Depression, a treatable cause of excess morbidity and mortality, was
      undertreated in all groups studied. However, treatment rates may be improving.
      The prevalent use of anxiolytics and hypnotics for depressed patients is
      problematic.

PMID- 11994937
TI  - Service contact and psychopathology in very-late-onset schizophrenia-like
      psychosis: the effects of gender and ethnicity.
AB  - BACKGROUND: Epidemiological data on very-late-onset (>60 years) schizophrenia
      like psychosis (SLP) are scarce. There are only two published follow-up studies.
      OBJECTIVE: To examine the associations of gender and ethnicity with health
      service contact and psychopathology in SLP. METHOD: We identified all new
      referrals of SLP to the Maudsley hospital between 1995-2000. Demographic details
      and information on the course of the illness were obtained from case notes. Those
      patients who agreed to take part were seen at home and assessed with respect to
      psychopathology and neurological side effects. RESULTS: The median duration of
      illness at the time of assessment was 3 years (range 1-6 years). Male patients
      were more likely to be admitted to hospital compulsorily and to be lost to follow
      up than female patients. Caribbean-born patients were more likely to refuse to
      take part than British-born patients. Of the 26 (48%) patients who were
      interviewed, 38% were experiencing paranoid symptoms, 94% of patients receiving
      medication were in regular contact with a community psychiatric nurse (CPN).
      Treatment response was dose related and was not increased by the use of a depot.
      CONCLUSION: The effects of gender and ethnicity on outcome need to be further
      investigated through larger studies. High loss to follow-up amongst male patients
      may be indicative of a poor prognosis. Regular contact with a CPN may be more
      important than the use of a depot in maintaining treatment response.

PMID- 11994938
TI  - Clock drawing test in mild and moderate dementia of the Alzheimer's type: a
      comparative and correlation study.
AB  - OBJECTIVES: (a) To compare two different clock drawing tests (CDTs) in mild and
      moderate dementia of the Alzheimer's type (DAT); (b) To examine presumed
      correlation between these CDTs and some demographic, cognitive and activities of
      daily living (ADL) variables in mild and moderate DAT. METHODS: Cross-sectional
      study. Psychogeriatric outpatient clinic. 49 DAT patients, total; 26-mild, 23
      moderate, mean age 77.8 and 80.6, respectively. Evaluations included the Mini
      Mental State Examination (MMSE), the Cambridge Cognitive Examination (CAMCOG),
      the Instrumental Activities of Daily Living Scale (IADL), and a Basic Activities
      of Daily Living (BADL)-dressing subscale. Severity of dementia was determined
      with the Clinical Dementia Rating (CDR). Each clock was blindly scored by the
      same investigator, according to Shulman's and Freedman's methods. RESULTS: Mild
      and moderate DAT groups were similar in age, gender and education. Performance on
      Shulman's clock was similar between groups while moderate DAT subjects performed
      significantly worse on Freedman's clock compared to mild DAT patients. Both
      clocks correlated highly in mild and moderate DAT. CDT scores correlated
      significantly with age and education only in mild DAT. Neither clock correlated
      with ADLs in either stage of dementia severity. CDTs correlated with the MMSE
      score, and the CAMCOG score in mild DAT, and only with the CAMCOG score in
      moderate DAT. These correlations were still significant after controlling for age
      and education. CONCLUSIONS: Different aspects of cognition and dementia severity
      are reflected depending on how a clock drawing is scored. Some scoring systems
      may have greater sensitivity than others in monitoring progression of cognitive
      deterioration. Correlation between different CDTs and the variables studied
      (demographic, cognitive, ADLs), when present, is not ubiqitous and changes with
      the dementia severity.

PMID- 11994939
TI  - Post stroke depression, first year post stroke, in middle band patients.

PMID- 11994940
TI  - Cancer mortality among elderly patients with brief psychotic disorder.

PMID- 11994941
TI  - Fewer hours of care yet undiminished caregiver burden with new long-term care
      insurance in Japan.

PMID- 11994942
TI  - SNRI and hyponatremia.

PMID- 11994943
TI  - Interventions in Alzheimer's disease.

PMID- 11994944
TI  - Current awareness in geriatric psychiatry.

PMID- 11994956
TI  - Near infrared spectroscopy in the evaluation of skeletal muscle disease.

PMID- 11994957
TI  - Motoneurons: A preferred firing range across vertebrate species?
AB  - The term "preferred firing range" describes a pattern of human motor unit (MU)
      unitary discharge during a voluntary contraction in which the profile of the
      spike-frequency of the MU's compound action potential is dissociated from the
      profile of the presumed depolarizing pressure exerted on the unit's spinal
      motoneuron (MN). Such a dissociation has recently been attributed by inference to
      the presence of a plateau potential (PP) in the active MN. This inference is
      supported by the qualitative similarities between the firing pattern of human MUs
      during selected types of relatively brief muscle contraction and that of
      intracellularly stimulated, PP-generating cat MNs in a decerebrate preparation,
      and turtle MNs in an in vitro slice of spinal cord. There are also similarities
      between the stimulus-response behavior of intracellularly stimulated turtle MNs
      and human MUs during the elaboration of a slowly rising voluntary contraction.
      This review emphasizes that there are a variety of open issues concerning the PP.
      Nonetheless, a rapidly growing body of comparative vertebrate evidence supports
      the idea that the PP and other forms of non-linear MN behavior play a major role
      in the regulation of muscle force, from the lamprey to the human.

PMID- 11994958
TI  - Laboratory diagnosis of metabolic myopathies.
AB  - The metabolic myopathies are a heterogeneous group of disorders inherited by a
      variety of modes that include gene defects in both the nuclear and mitochondrial
      genomes. Many factors impact on the expression of the pathogenic mutations that
      cause these disorders including genetic background, environmental factors, and
      coexisting disorders. Molecular technology has greatly improved the ability to
      make definitive diagnoses in many of the metabolic myopathies in the last decade
      and particularly has demonstrated that the wide diversity in the severity of
      mutations contributes to understanding genotype-phenotype correlations. In some
      cases, molecular testing obviates the necessity to perform an invasive muscle
      biopsy. However, it is also clear that the diagnostic yield from molecular
      testing is incomplete and particularly low among the mitochondrial myopathies as
      a group, ranging from approximately 6% to 19% in well-classified high-risk
      groups. Therefore, it is often essential to combine clinical, biochemical,
      histopathologic, and molecular data for each patient in order to arrive at a
      definitive diagnosis. The approach to the laboratory diagnosis of metabolic
      myopathies is described emphasizing both noninvasive and invasive testing,
      highlighting the molecular methodologies with the benefits and disadvantages of
      each technology, and documenting how to determine whether patients have
      coexisting disorders.

PMID- 11994959
TI  - Near infrared muscle spectroscopy in patients with Friedreich's ataxia.
AB  - Friedreich's ataxia is a progressive neurodegenerative disorder of the afferent
      cerebellar pathways associated with mitochondrial dysfunction at the cellular
      level. We have used noninvasive continuous near infrared muscle spectroscopy
      (NIRS) to investigate the delivery and utilization of oxygen in response to
      exercise in this disorder. Patients performed an incremental treadmill walking
      protocol in which levels of muscle deoxygenation or oxygenation were continuously
      measured in the medial calf muscle. The kinetics of recovery from exercise
      induced deoxygenation, called the half-time of recovery (t(1/2)) were determined.
      The t(1/2) was prolonged in patients with Friedreich's ataxia compared with
      controls, and the degree of prolongation correlated with the length of the
      shorter GAA repeat, a genetic measure that correlates with the age of onset of
      disease. The t(1/2) also correlated inversely with patient age and with the
      maximum treadmill speed attained. Several patients also displayed features
      consistent with inadequate oxygen utilization by muscle. These results suggest
      that NIRS may be an effective tool for monitoring the biochemical and functional
      features of Friedreich's ataxia in parallel.

PMID- 11994960
TI  - Monofocal motor neuropathy: Improvement with intravenous immunoglobulin.
AB  - Multifocal motor neuropathy (MMN) is a chronic, immune-mediate, peripheral
      myelinopathy. Inherent in its name, MMN implies involvement of two or more motor
      nerves. We report three patients with weakness and partial motor conduction block
      restricted to a single nerve and localized to sites that are not at risk for
      entrapment or compression injury. None of the patients had sensory involvement
      and all showed a favorable response to intravenous immunoglobulin therapy. Based
      on these observations and reports of three additional patients, we believe that
      monofocal motor neuropathy is a partial form of MMN and should be treated as
      such.

PMID- 11994961
TI  - Improved viability of latissimus dorsi muscle grafts after electrical
      prestimulation.
AB  - Surgical mobilization of the latissimus dorsi muscle (LDM) produces fiber
      degeneration, particularly in the distal part of the graft, that may compromise
      its function in clinical applications such as dynamic cardiomyoplasty. In five
      rats, the left LDM was stimulated continuously at 10 HZ. After 5 weeks, vessels
      perforating the chest wall were divided and the left LDM was mobilized as a
      pedicle graft based on the thoracodorsal artery. Twenty-four hours later, animals
      were killed and left and right LDMs were incubated with the vital stain nitroblue
      tetrazolium. Five control rats underwent a similar procedure without
      prestimulation. Mobilization of the LDM resulted in a loss of viability in the
      distal third of the muscle graft. This was reduced significantly by
      prestimulation (P = 0.006). Blood flow to the distal LDM graft is known to be
      augmented by electrical stimulation in situ before mobilization; the present
      results show that there is an associated enhancement of viability. The clinical
      implications of this finding are discussed.

PMID- 11994962
TI  - Training by low-frequency stimulation of tibialis anterior in spinal cord-injured
      men.
AB  - The tibialis anterior muscle of nine paraplegic men was chronically stimulated (2
      6 h per day; at 10 Hz, 5 s on, 5 s off) under isometric loading conditions for 5
      days per week for 4 weeks. After 4 weeks of training, muscle fatigue resistance
      in an electrically evoked test had increased by an average of 75% (P <.01, n =
      9), but there were no changes in the relative composition of the three myosin
      heavy chain (MHC) isoforms. Five of the subjects continued training for an
      additional 5 weeks (2 h per day, 3 days per week). Although there was a tendency
      for twitch time to peak torque to increase after this additional period, no
      change occurred in relative MHC isoform content. However, in situ hybridization
      analysis revealed that even after 2 weeks of stimulation, there was evidence of
      upregulation of the mRNA for the MHC-I isoform and downregulation of the MHC-IIX
      isoform, a development that continued in weeks 4 and 9. This study provides
      evidence, at the level of gene transcription, that a fast-to-slow change in MHC
      isoform composition may be possible in human muscle when its usage is
      significantly increased.

PMID- 11994963
TI  - Is the cutaneous silent period an opiate-sensitive nociceptive reflex?
AB  - In humans, high-intensity electrical stimuli delivered to the fingers induce an
      inhibitory effect on C7-T1 motoneurons. This inhibitory reflex, called the
      cutaneous silent period (CSP) is considered a defense response specific for the
      human upper limbs. It is not clear whether the CSP-like other defense responses
      such as the corneal reflex and the R III reflex-is an opiate-sensitive
      nociceptive reflex. Because opiates suppress some, but not all, nociceptive
      reflexes, we studied the effect of the narcotic-analgesic drug fentanyl on the
      CSP and the R III reflex. The CSP was recorded from the first dorsal interosseous
      (FDI) muscle in seven normal subjects during voluntary contraction, before and 10
      and 20 min after fentanyl injection. To assess possible fentanyl-induced changes,
      we also tested the effect of finger stimulation on motor evoked potentials (MEPs)
      elicited in the FDI muscle by transcranial magnetic stimulation before and after
      fentanyl injection. Fentanyl-induced changes were also studied on the R III
      reflex recorded from the biceps femoris muscle. Fentanyl, as expected, suppressed
      the R III reflex but failed to change the inhibitory effect of finger stimulation
      on FDI motoneurons. Finger stimulation reduced the size of MEPs in the FDI, and
      fentanyl injection left this inhibitory effect unchanged. The differential
      fentanyl-induced modulation of the CSP and R III reflex provides evidence that
      the CSP circuit is devoid of mu-opiate receptors and is therefore an opiate
      insensitive nociceptive reflex, which may be useful in the assessment of central
      acting, non-opioid drugs.

PMID- 11994964
TI  - Possible pathogenic role of muscle cell dysfunction in motor neuron death in
      spinal muscular atrophy.
AB  - We have previously shown that myofibers formed by fusion of muscle satellite
      cells from spinal muscular atrophy (SMA) I or II undergo degeneration 1 to 3
      weeks after innervation by rat embryonic spinal cord explants, whereas normal
      myofibers survive for several months. In the "muscle component" of the coculture,
      the only cells responsible for the degeneration are the SMA muscle satellite
      cells. Moreover, SMA muscle satellite cells do not fuse as rapidly as do normal
      muscle satellite cells. To determine whether death of muscle cells precedes that
      of motor neurons, we studied the origin and kinetics of release of apoptotic
      microparticles. In SMA cocultures, motor neuron apoptosis occurred before
      myofiber degeneration becomes visible, indicating that SMA myofibers were unable
      to sustain survival of motor neurons. In normal cocultures, motor neuron
      apoptosis occurred 4 days after innervation. However, it did not continue beyond
      2 days. These results strengthen the hypothesis that SMA is due to a defect in
      neurotrophic muscle cell function.

PMID- 11994965
TI  - Disease progression in amyotrophic lateral sclerosis: predictors of survival.
AB  - Predicting the rate of disease progression has become important as trials of new
      medical treatments for amyotrophic lateral sclerosis (ALS) are planned. Bulbar
      onset, early impairment of forced vital capacity, and older age have all been
      associated with shorter survival. We performed a retrospective study to compare
      survival factors with disease progression in a German ALS population. We analyzed
      disease progression in 155 patients at intervals of 4 months over a period of 3
      years. To evaluate disease progression, the ALS functional rating scale (ALS
      FRS), forced vital capacity (FVC%), and a Medical Research Council (MRC) compound
      score based on a nine-step modified MRC scale were used. We compared age (< 55
      years vs. > or =55 years), different sites of disease onset (bulbar vs. limb),
      and gender to the rate of disease progression and performed survival analyses. No
      overall significant difference could be detected when analyzing these subgroups
      with regard to disease progression. By contrast, significantly longer survival
      was observed in the younger age group (56 months vs. 38 months, P < 0.0001) and
      in patients with limb-onset disease (51 months vs. 37 months, P = 0.0002). Using
      Cox analyses values we found that the declines of ALS-FRS, FVC%, and MRC compound
      score were predictive of survival (P < 0.0001, P = 0.002, and P = 0.003,
      respectively). Future studies are needed to clarify whether nonspecific factors
      including muscle atrophy, dysphagia, and coexisting diseases influence prediction
      of survival in ALS patients. A more precise set of predictors may help to better
      stratify patient subgroups for future treatment trials.

PMID- 11994966
TI  - The action of Lambert-Eaton myasthenic syndrome immunoglobulin G on cloned human
      voltage-gated calcium channels.
AB  - In the Lambert-Eaton myasthenic syndrome (LEMS), immunoglobulin G (IgG)
      autoantibodies to presynaptic voltage-gated calcium channels (VGCCs) at the
      neuromuscular junction lead to a reduction in nerve-evoked release of
      neurotransmitter and muscle weakness. We have examined the action of LEMS IgGs on
      cloned human VGCCs stably expressed in transfected human embryonic kidney
      (HEK293) cell lines: 10-13 (alpha(1A-2), alpha(2b)delta, beta(4a)) and C2D7
      (alpha(1B-1), alpha(2b)delta, beta(1b)). All LEMS IgGs studied showed surface
      binding to [(125)I]-omega-CTx-MVIIC-labeled VGCCs in the alpha(1A) cell line and
      two of six IgGs showed surface binding to [(125)I]-omega-CTx-GVIA-labeled VGCCs
      in the alpha(1B) cell line. We next studied the effect of LEMS IgGs (2 mg/ml) on
      whole-cell calcium currents in the alpha(1A) and alpha(1B) cell lines. Overnight
      treatment of alpha(1A) (10-13) cells with LEMS IgGs led to a significant
      reduction in peak current density without alteration of the current-voltage
      relationship or the voltage dependence of steady-state inactivation. In contrast,
      LEMS IgGs did not reduce peak current density in the alpha(1B) cell line. Overall
      these data demonstrate the specificity of LEMS IgGs for the alpha(1A) cell line
      and suggest that LEMS IgGs bind to and downregulate VGCCs in this cell line.
      Although several LEMS IgGs can be shown to bind to the alpha(1B) (C2D7) cell
      line, no functional effects were seen on this channel.

PMID- 11994967
TI  - Electromyography of sternocleidomastoid muscle in ALS: a prospective study.
AB  - Needle electromyography (EMG) of the tongue is difficult to perform because of
      frequent uncontrollable movement. We chose the sternocleidomastoid (SCM) muscle
      as a possible alternative for assessing the involvement of the rostral neuraxis
      in amyotrophic lateral sclerosis (ALS). We prospectively studied 21 ALS patients
      during our initial diagnostic evaluation. EMG parameters that we recorded
      included the presence of abnormal spontaneous activity, pattern of motor unit
      potential recruitment, and configuration of motor unit action potentials. For the
      six patients with bulbar-onset ALS, three had abnormalities in the SCM and three
      had abnormalities in the tongue. In contrast, for the 15 patients with limb-onset
      ALS, 9 had abnormalities in the SCM, and only 3 had abnormalities in the tongue.
      Our results demonstrate the utility of needle EMG of the SCM in the evaluation of
      ALS. EMG of the SCM carries a similar sensitivity as the tongue in ALS patients
      with bulbar symptoms, but is more sensitive than the tongue in patients without
      bulbar symptoms. SCM innervation includes the rostral cervical cord and
      brainstem, and EMG abnormalities in this muscle support a diffuse involvement,
      which is unique to ALS.

PMID- 11994968
TI  - Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated
      by the beta2-adrenergic receptor.
AB  - Analyses were performed to evaluate the roles of the beta1- and beta2-adrenergic
      receptors in the skeletal muscle hypertrophy and anti-atrophy response to the
      beta-adrenergic agonist, clenbuterol. Treatment of wild-type mice with
      clenbuterol resulted in statistically significant hypertrophy of the innervated
      tibialis anterior and medial gastrocnemius muscles and inhibition of denervation
      induced atrophy of these muscles. Treatment of beta1-adrenergic receptor knockout
      mice with clenbuterol also resulted in statistically significant hypertrophy of
      the innervated tibialis anterior and medial gastrocnemius muscles and inhibition
      of denervation-induced atrophy of these muscles. In contrast, in beta2-adrenergic
      receptor knockout mice and in mice lacking both the beta1- and beta2-adrenergic
      receptors, clenbuterol treatment did not result in hypertrophy of the innervated
      tibialis anterior and medial gastrocnemius muscles, nor did it inhibit
      denervation-induced atrophy in these muscles. Together these data demonstrate
      that the beta2-adrenergic receptor is responsible for both the skeletal muscle
      hypertrophy and anti-atrophy effects of the beta-adrenergic agonist clenbuterol.

PMID- 11994969
TI  - Muscle strength following direct injection of doxorubicin into rabbit
      sternocleidomastoid muscle in situ.
AB  - Direct intramuscular injection of doxorubicin results in permanent myofiber loss.
      A previous phase I trial demonstrated that such injections could successfully
      treat blepharospasm and hemifacial spasm. Our previous in vitro study
      demonstrated that doxorubicin resulted in a dose-dependent reduction in isometric
      force generation in sternocleidomastoid muscle in rabbits. This present study
      examined alterations in force generation in these treated muscles in situ, i.e.,
      with the blood and nerve supply intact. Two months after a single doxorubicin
      injection, functional changes in peak twitch, tetanic force generation, and
      fatigue rate were assessed in control and doxorubicin-treated sternocleidomastoid
      muscles in rabbits. Peak force measurements were reduced in the treated muscles.
      These reductions in muscle strength were significantly greater at tetanic peak
      amplitudes. Fatigue rate was not altered by doxorubicin treatment of the
      sternocleidomastoid muscles. These findings support the potential clinical use of
      doxorubicin chemomyectomy for the treatment of patients with cervical dystonia.

PMID- 11994970
TI  - Intravascular lymphomatosis.
AB  - Intravascular lymphomatosis, also known as endovascular lymphoma or angiotropic
      large cell lymphoma, is a rare malignancy typically diagnosed at autopsy. We
      describe a case in which the diagnosis was made at an early stage. Specific
      electrodiagnostic findings suggested concomitant polyneuropathy and myopathy.
      Suspicion of a paraneoplastic syndrome during electrodiagnostic testing prompted
      muscle biopsy, which revealed myopathy due to the direct infiltration of
      neoplastic cells. Resultant treatment with a standard chemotherapy regimen not
      only increased the patient's survival, but also improved neurological function.

PMID- 11994971
TI  - Lack of the C-terminal domain of nebulin in a patient with nemaline myopathy.
AB  - The most common autosomal recessive form of nemaline myopathy is due to mutations
      in the nebulin gene. Among eight patients studied, we identified one, a 14-year
      old girl, with a specific pattern of diffuse rods in muscle fibers. Western blot
      analysis detected absence of the C-terminal domain of nebulin. Protein analysis
      may represent a good screening method to direct molecular studies in the case of
      very large and complex genes such as the large 1298 kb nebulin gene.

PMID- 11994972
TI  - Intercostal neuralgic schwannoma: a case report.

PMID- 11994973
TI  - Poly-Hill sign in facioscapulohumeral dystrophy.

PMID- 11994975
TI  - Relationship of venous thromboembolism and myocardial infarction with the renin
      angiotensin system in African-Americans.
AB  - Genetic polymorphisms/mutations associated with venous thrombosis have largely
      been confined to the genes that encode for proteins in either the coagulant or
      the anticoagulant pathway. Although genetic alterations in the renin-angiotensin
      system have been reported to have a role in myocardial infarction and
      hypertension, there is recent evidence to suggest that there may also be an
      association with venous thrombosis. To extend our earlier observation of an
      association between the ACE DD genotype in African-American males and venous
      thrombosis, other genes in the renin-angiotensin pathway were investigated for
      possible disease association and were compared with African-Americans with
      myocardial infarction. African-American patients with a documented history of
      venous thrombosis or a history of myocardial infarction were eligible for
      participation as cases in the study. Control subjects were African-American
      outpatients attending a clinical laboratory for routine blood tests who had
      comparable age and gender distributions to the cases. Persons with a history of
      myocardial infarction, stroke, or thrombosis were excluded. Genes that were
      analyzed for known polymorphisms included angiotensinogen, angiotensin-converting
      enzyme (ACE), and the angiotensin II type I receptor. Our results showed that the
      ACE DD genotype was also associated with MI in African-American males but not in
      females. Racial/ethnic and sex differences were also found with respect to the
      genotype distribution of the ACE 4656(CT)(2/3) polymorphism. It was observed that
      the 2/2 genotype had a protective effective in males for myocardial infarction
      and venous thrombosis. The data also demonstrated that the allele frequencies of
      the A1166C variant of the angiotensin II type I receptor were different in
      African-Americans as compared to Caucasians.

PMID- 11994976
TI  - Effect of all-trans-retinoic acid on the hypercoagulable state of patients with
      breast cancer.
AB  - To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate the
      hemostatic system in patients with solid tumors, we studied patients with locally
      advanced breast cancer who were enrolled in a Phase Ib study of ATRA +/-
      Tamoxifen (Tam). In this study, two groups of 15 patients/each were treated for
      21 days before operation with ATRA at three doses (15, 45, or 75 mg/m(2)/day on
      alternate days) given alone (group 1) or in combination with Tam (group 2). One
      additional group received Tam alone. Plasma samples were evaluated for
      hypercoagulation markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t
      PA, PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer
      patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than control
      subjects. During treatment, in the patients given ATRA alone, hypercoagulation
      markers appeared unmodified. Instead, subjects given Tam alone had a significant
      elevation of FVIIa, F1+2, and TAT versus baseline. However, in the ATRA + Tam
      groups, hypercoagulation markers were decreased compared with Tam alone. These
      results suggest that in selected conditions, pre-operative ATRA may modulate the
      hypercoagulable state of breast cancer patients.

PMID- 11994977
TI  - Therapeutic plasma exchange in Mexico: experience from a single institution.
AB  - Information about therapeutic plasma exchange (TPE) in developing countries is
      lacking. We report our experience with TPE performed for different indications
      during a 7-year period. We reviewed all TPE procedures performed in our
      institution during a 7-year period. Patients were divided in four groups
      according to the following indications: thrombotic microangiopathies (TM),
      myasthenia gravis (MG), polyneuropathies (PNP), and miscellaneous indications
      (MI). Clinical outcome (CO) and complications were evaluated. Eighty-seven
      procedures were carried out in 81 patients, for a total of 376 TPE sessions.
      Eighty-two procedures were analyzed for CO. In the group of TM we had 65% overall
      response rate (ORR): 35% complete response (CR) and 30% partial response (PR).
      Six (28.6%) patients died in this group. In the MG group we had 90% ORR: 69% CR
      and 21% PR. In the PNP group we had 78% ORR: 56% CR and 22% PR. In the MI group
      we had 92% ORR: 59% CR and 33% PR. We observed 47 adverse reactions in 40 (46%)
      procedures performed in 38 (47%) patients. This represented 12.5% of sessions. We
      had seven major complications leading to TPE discontinuation; this represented 8%
      of the procedures and 1.8% of sessions. One patient (0.2%) died during TPE. Our
      overall results are acceptable. In the TM group our results are somewhat lower
      than in other published reports, but in MG and PNP our results are similar to
      other published reports. Our complication rate is similar to that reported by
      others. Careful selection of patients and protocols is crucial to achieve maximum
      benefit from TPE programs in countries where plasmapheresis facilities are not
      widely available.

PMID- 11994978
TI  - Role of the microenvironment in promoting angiogenesis in acute myeloid leukemia.
AB  - Angiogenesis is a crucial event in the survival and progression of solid tumors.
      To determine whether angiogenesis in acute myeloid leukemia (AML) is an intrinsic
      property of leukemic cells, the vascularity of bone marrow biopsies was
      determined. Bone marrow vascularity in newly diagnosed or post-chemotherapy AML
      patients was increased 4-fold (P < 0.01) and 8.7-fold (P < 0.01), respectively,
      relative to controls. Vascular endothelial growth factor (VEGF) expression by AML
      blast cells was assessed by immunohistochemistry, and bone marrow cell
      supernatants were assayed for secretion of VEGF, fibroblast growth factor-2 (FGF
      2), and endostatin by enzyme-linked immunosorbent assay. Diffuse cytoplasmic and
      strong extracellular VEGF immunoreactivity was seen in bone marrow aspirates from
      AML patients, but not controls. In contrast, there was no difference in the
      levels of VEGF, FGF-2, and endostatin secreted by mononuclear cells cultured from
      bone marrows of AML patients compared to normal controls following two days of
      culture in vitro. Total angiogenic potential of bone marrow cell supernatants was
      assessed by endothelial sprouting in vitro and by a chick chorioallantoic
      membrane assay. No differences were found between 2-day conditioned medium from
      normal and AML bone marrow mononuclear cells in either assay. Our data show a
      discrepancy between bone marrow vascularity and VEGF expression in vivo and VEGF
      expression and angiogenesis from 2-day conditioned medium ex vivo. This suggests
      that angiogenesis in AML likely represents a response to microenvironmental
      factors in vivo, rather than being an intrinsic property of leukemic cells.

PMID- 11994979
TI  - Epstein-Barr virus-associated peripheral T-cell and NK-cell proliferative
      disease/lymphoma: clinicopathologic, serologic, and molecular analysis.
AB  - Peripheral T-cell proliferative disease/lymphoma is a group of diseases which
      exhibits heterogeneity in clinical manifestations, pathological findings and
      outcomes. They are highly associated with the Epstein-Barr virus (EBV) infection.
      It is likely that EBV plays an important role in the tumorigenesis. From January
      1997 through April 2000, we identified 100 patients. One hundred healthy age- and
      sex- matched controls were selected. Serologic tests for the EBV infection and
      the study of EBV genomes in circulating non-T cells (CD3- cells), T cells (CD3+
      cells), and T-cell subsets (CD4+ and CD8+ cells) were performed. The main
      features were prolonged fever, weight loss, hepatosplenomegaly, lymphadenopathy,
      multiorgan involvement, anemia, and high serum alkaline phosphatase and lactate
      dehydrogenase. Fifty-one patients had an aggressive course and died; median
      survival was 21 months. Chemotherapy was not effective in improving survival.
      Anti-viral capsid antigen-IgG and anti-early antigen-IgG were significantly
      elevated, whereas there was no significant difference in anti-EBV nuclear
      antigen. EBV internal repeat-1 region (IR-1) in the peripheral blood CD3+ cells
      was detected in 65% of the patients but in none of the controls. For the CD3-
      cells, EBV IR-1 was detected in 88% of the patients and 50% of the controls.
      Among twenty-five patients whose CD3+ cells were positive for EBV IR-1, 6 (24%)
      showed EBV IR-1 in only CD4+ cells, 6 (24%) in only CD8+ cells, and 13 (52%) in
      both CD4+ and CD8+ cells. The 30-bp deletion variant of the EBV latent membrane
      protein-1 gene was significantly higher in the patients than in the controls.
      These data support the chronic infective process. The EBV which is dormant in non
      T cells may infect T cells and contribute to the pathogenesis of disease in a
      select group of patients.

PMID- 11994980
TI  - all-trans-Retinoic acid-induced expression and regulation of retinoic acid 4
      hydroxylase (CYP26) in human promyelocytic leukemia.
AB  - all-trans-Retinoic acid (ATRA) induces complete remission in majority of patients
      with acute promyelocytic leukemia (APL). However, accelerated metabolism of ATRA
      that is induced by chronic daily administration of oral ATRA has been implicated
      as one of the mechanisms leading to a reduced sensitivity or resistance to ATRA
      therapy. We investigated the expression and regulation of CYP26, a novel p450
      enzyme, which is highly specific for ATRA, in promyelocytic leukemia cells (NB4
      and HL-60). We found that treatment of NB4 cells with a pharmacological
      concentration of ATRA (1 microM) induced rapid and dose-dependent expression of
      CYP26 mRNA. The CYP26 expression returned to pretreatment levels in both cells
      after ATRA was removed from the media. Retinoic acid receptor-alpha (RARalpha)
      specific antagonist (CD2503) totally abolished the ATRA-induced expression of
      CYP26 mRNA in HL-60 and NB4 cells. Furthermore, HL-60R, a HL-60 subclone
      expressing nonfunctional RAR because of a point mutation in the ligand-binding
      domain of RARalpha, failed to show CYP26 mRNA expression in response to ATRA.
      ATRA-induced expression of CYP26 was restored in HL-60R cells retrovirally
      transduced with RARalpha, but not in those cells transduced with the other
      retinoid receptors. In conclusion, ATRA induces expression of CYP26 in myeloid
      and promyelocytic leukemia cells and this expression is modulated by RARalpha.
      The induction of CYP26 expression by ATRA treatment might be related to a
      substrate-driven feedback mechanism to regulate intracellular concentrations of
      ATRA and its over expression in some clones may be partly responsible for reduced
      sensitivity or resistance to ATRA therapy.

PMID- 11994981
TI  - Aggressive growth of epithelial carcinomas following treatment with nucleoside
      analogues.
AB  - Two patients, one with B-cell chronic lymphocytic leukemia (CLL) and one with
      hairy-cell leukemia (HCL), were treated with immunosuppressive chemotherapy. The
      patient with CLL was a 54-year-old female, who had had a squamous cell carcinoma
      (SCC) excised from her forehead 5 months before receiving the first course of
      fludarabine. During the fludarabine treatment, the patient developed a local SCC
      relapse and metastases in the neck. The carcinoma was treated by excision and
      radiotherapy, and further fludarabine treatment was withheld. Nevertheless, the
      SCC metastasized aggressively and the patient died 3 months after the start of
      fludarabine treatment, primarily due to respiratory failure. The autopsy revealed
      heavy SCC infiltrations involving the lungs, pleura, mediastinum, pericardium,
      and liver. The patient with HCL was a 69-year-old male. At the time of diagnosis
      of HCL, the patient had two solid tumors in the liver containing poorly
      differentiated epithelial carcinoma cells of unknown origin. During treatment
      with 2-chlorodeoxyadenosine (2CdA), the tumors in the liver rapidly spread in
      multiple intrahepatic metastases, followed by liver failure and death within 1
      month. Fludarabine and 2CdA cause a substantial suppression of all lymphocyte
      subsets, in particular the T-cell line. T-lymphocytes are believed to be
      responsible for the usually slow growth and the low metastatic rate of the SCC
      skin lesions. It is therefore assumed that fludarabine and 2CdA in these two
      cases triggered an exacerbation of both tumors due to the T-cell depletion.

PMID- 11994982
TI  - Progressive multifocal leukoencephalopathy after fludarabine therapy for low
      grade lymphoproliferative disease.
AB  - Fludarabine is becoming the initial therapy for low-grade lymphoproliferative
      malignancies, such as CLL and follicular lymphoma. Fludarabine is highly
      immunosuppressive in addition to being myelosuppressive and has been associated
      with neurotoxicity. Progressive multifocal leukoencephalopathy (PML) is an
      infection with JC virus of the white matter of the central nervous system seen
      mostly in immunosuppressed patients. We describe two patients treated with
      fludarabine who developed PML. Immunolabeling was positive for JCV in both
      patients, but PCR was repeatedly negative in one of them. We suggest that
      fludarabine may increase the risk of PML in patients with lymphoproliferative
      diseases.

PMID- 11994983
TI  - Unusual presentation of multiple myeloma with unilateral visual loss and numb
      chin syndrome in a young adult.
AB  - A 39-year-old man presented with unilateral visual loss as the first sign of
      multiple myeloma (MM). His visual loss was due to a plasmacytoma in the sphenoid
      sinus compressing the optic nerve with resultant optic nerve atrophy. Shortly
      after this presentation he developed numb chin syndrome due to a mandibular
      plasmocytoma compressing the mental nerve. His MM progressed rapidly despite
      treatment with high-dose steroids and alkylating agents and he required
      allogeneic bone marrow transplantation in order to achieve a remission. We
      reviewed the published medical literature on the presentation of MM with visual
      impairment and present a summary in tabular form in this paper. This is the first
      reported case of MM presenting with isolated complete visual loss due to
      intracranial extrinsic compression of the optic nerve since the advent of modern
      cross-sectional imaging. Multiple myeloma needs to be included in the
      differential diagnosis of cranial neuropathies and skull base neoplasms even in
      adults under 40 years of age.

PMID- 11994984
TI  - Successful long-term control with lamivudine against reactivated hepatitis B
      infection following intensive chemotherapy and autologous peripheral blood stem
      cell transplantation in non-Hodgkin's lymphoma: experience of 2 cases.
AB  - It is well documented that cytotoxic treatment in patients carrying the hepatitis
      B virus (HBV) enhances the risk of severe hepatic damage. Recently lamivudine has
      been reported to be effective in suppressing the replication of HBV under such
      conditions. Here we report two cases with HBV carrier status and with non
      Hodgkin's lymphoma who were successfully treated with high-dose chemotherapy
      followed by autologous peripheral blood stem cell transplantation with the
      administration of lamivudine to prevent HBV flare-up. The antiviral effect of
      lamivudine was fair, and no objective side effect was experienced during the
      transplant procedure. Both patients were followed carefully for more than a year
      without the appearance of the resistant virus. The rebound phenomenon in which
      HBV proliferates abruptly has not been experienced after withdrawal of
      lamivudine. We suggest that lamivudine is indicated both in the treatment of HBV
      viremia and in the prevention of proliferation of HBV in patients with HBV
      carrier status undergoing high-dose myeloablative chemotherapy.

PMID- 11994985
TI  - Acquired von Willebrand disease--hemostatic management of major orthopedic
      surgery with high-dose immunoglobulin, desmopressin, and continuous factor
      concentrate infusion.
AB  - Acquired von Willebrand disease (aVWD) is a rare bleeding disorder that mimics
      congenital VWD in previously healthy individuals; it is most frequently
      associated with monoclonal gammopathy. Hemostatic therapy of aVWD is challenging
      due to the extremely shortened half-life of endogenous and exogenous VWF. High
      dose intravenous immunoglobulin (ivIG) is recommended as the treatment of choice,
      usually rapidly normalizing coagulation; but in case of failure, alternative
      treatment options are not well explored. We report successful major orthopedic
      surgery in a 61-year-old woman with multiple myeloma IgG lambda and aVWD. IvIG
      alone failed to correct hemostasis. However, ivIG pretreatment improved the VWF
      ristocetin cofactor (VWF:RCo) half-life from only 1.5 hr to more than 4 hr,
      allowing desmopressin infusions twice daily to maintain sufficient VWF:RCo
      levels. Because of diminishing desmopressin effect, we attempted for the first
      time in aVWD a continuous VWF/FVIII infusion (Haemate HS), 2.1-2.7 FVIII U/kg/hr
      or 51-64 U/kg/day, respectively 4.6-6.0 VWF:RCo U/kg/hr or 110-145 U/kg/day) to
      reach constant factor levels. The steady-state clearance was 2.4 mL/kg/hr for
      FVIII:C and 13.5 mL/kg/hr for VWF:RCo. During surgery, VWF:RCo, FVIII:C, and PFA
      100 closure time were normalized. Until day 5, VWF:RCo was kept above 50%, from
      day 6 to 10 at least 30% activity were attained. FVIII:C levels were always >70%.
      The clinical course was uneventful without bleeding. Two weeks after hip surgery
      the patient was discharged from the hospital without complaints. The therapy
      described can be recommended as safe and feasible for further evaluation in aVWD
      patients who are hyporesponsive to ivIG treatment alone. Continuous VWF/FVIII
      infusion can improve substitution therapy in aVWD.

PMID- 11994986
TI  - New sporadic case of congenital dyserythropoietic anemia type III in an aged
      woman: detailed description of ultrastructural findings.
AB  - We describe a new case of congenital dyserythropoietic anemia (CDA) type III.
      This least common type of CDA was diagnosed at the age of 59 in a 70-year-old
      woman who suffered from a young age from mild macrocytic anemia, while the long
      follow up since diagnosis documented a benign clinical course. No family history
      of blood diseases was obtained and no anemia was documented in the medical
      records of any of her four children. The bone marrow (BM) examination on light
      microscopy revealed a severe erythroid hyperplasia with the presence of giant
      multinucleated erythroblasts. Ultrastructural examination of the BM disclosed the
      presence of many large multinucleated erythroblasts bearing a variety of
      ultrastructural findings: nuclear clefts, autophagic vacuoles, iron-loaded
      mitochondria, and intracytoplasmic myelin figures. In addition, extensive
      hyperlobulation of the nucleus and partial loss of nuclear membrane with
      "spilling" of nuclear material to the adjacent cytoplasm was also noted in some
      of the erythroblasts. These last two findings have not been previously described
      in CDA III.

PMID- 11994987
TI  - Lymphoplasmacytoid lymphoma presenting as severe osteoporosis.
AB  - We report four cases presenting with severe osteoporosis which on further
      investigation were found to have an underlying lymphoplasmacytoid lymphoma (LPL).
      Common secondary causes of osteoporosis were excluded in each case. Three of the
      cases responded to treatment with a biphosphonate. As these lymphomas share some
      common pathological and clinical features with multiple myeloma (MM) an
      association with osteoporosis is likely to represent more than a coincidental
      finding. The incidence of osteoporosis occurring with LPL will become clearer if
      routine imaging is carried out in patients at presentation. Issues relating to
      the treatment of the osteoporosis as well as the lymphoma arise in patients that
      present in this way. Based on the model of bone disease in MM, correlating serum
      levels of osteoclast activating cytokines such as interleukin-1 (IL-1),
      interleukin-6 (IL-6), and tumour necrosis factor (TNF) with the actual finding of
      bone disease provides a basis for future research into the pathogenesis and
      management of bone disease in these rare forms of low grade non-Hodgkin's
      lymphoma.

PMID- 11994988
TI  - Immune-mediated thrombocytopenia associated with valley fever.

PMID- 11994989
TI  - Title of legislation: family and Medical Leave Act of 1993 (FMLA).

PMID- 11994990
TI  - Breast health: what is it?

PMID- 11994991
TI  - Tobacco farmers vs. health care.

PMID- 11994992
TI  - Last acts--precepts of palliative care.

PMID- 11994993
TI  - Nurses and prevention: the leap into the 21st century.

PMID- 11994994
TI  - Nurses can impact the effects of Alzheimer's disease.
AB  - Nurses should be leaders in the effort to improve a health care crisis such as
      AD. By uniting, nurses have the ability to impact the effects of AD. Nurses can
      best do this by belonging to and supporting their professional organization,
      ANA/NCNA. Nurses should feel morally obligated to promote any action that
      improves public health and quality of life. In the role of clinician, nurses can
      benefit clients, caregivers, and society by promoting the client's optimal
      function. This can be done by involving them in therapeutic mental and/or
      physical exercises. Coordinating and collaborating with other disciplines, such
      as physical therapy can also be beneficial. In conclusion, with appropriate
      action, the nursing profession has the ability to impact the effects of AD on our
      society.

PMID- 11994995
TI  - Preventing neural tube defects in North Carolina: the nurse's role.

PMID- 11994996
TI  - Clinical outcomes, satisfaction, and psychotropic medication use in patients of
      certified specialists in psychiatric-mental health nursing: a brief report.

PMID- 11994998
TI  - ANA testifies at hearing on medical errors.

PMID- 11994997
TI  - North Carolina Board of Nursing questions regarding short staffing & abandonment.

PMID- 11994999
TI  - Quality Health Care Coalition Act.

PMID- 11995000
TI  - Nursing school enrollments decline.

PMID- 11995001
TI  - Professional Practice advocacy: a multipurpose approach to chaos in the health
      care system.

PMID- 11995002
TI  - Did nurses delegate Dr.'s orders for 'packing' to others?

PMID- 11995003
TI  - I.V. push of vesicants causes extravasation. Case on point: Iacano v. St. Peter's
      Medical Center, 334 N.J. Super. 547--NJ (2000).

PMID- 11995004
TI  - ND: did delay result in mother's comatose state?: nurse expert's testimony held
      'inadmissible'.

PMID- 11995005
TI  - TN: nurse assists in ambulating--patient falls: simple negligence or medical
      malpractice?

PMID- 11995006
TI  - Did nurses fail to 'give Procardia' as ordered? Case on point: Piro v. Chandler,
      2000 WL 1634167 So.2d--LA.

PMID- 11995007
TI  - Clinical excellence exemplar.

PMID- 11995008
TI  - A tribute to my clinical mentors.

PMID- 11995009
TI  - Knowles II ruling may limit nursing home litigation.

PMID- 11995010
TI  - AIDS in Aruba: the Caribbean experience.

PMID- 11995011
TI  - You must be a great nurse!

PMID- 11995012
TI  - Professional practice advocacy.

PMID- 11995013
TI  - Health issues for the 2000 election.

PMID- 11995014
TI  - Can you recognize Munchausen's syndrome by proxy?

PMID- 11995015
TI  - Did nurse-midwives call for help in time? Case on point: Anderson v. Ewing, 2000
      WL 1283810 So.2d - FL (2000).

PMID- 11995016
TI  - TN: surgical nurse knocked down by patient: 'certainty of causation' not required
      for comp.

PMID- 11995017
TI  - MA: OR nurse claims comp. for MCS: comp. denied due to 'medical uncertainty'.

PMID- 11995018
TI  - Did nurse call Dr. twice: did Dr. have duty to check Pt.? Case on point: Stubbs
      v. Ray, 2000 WL 125325 S.E.2d - GA (2000).

PMID- 11995019
TI  - Nursing issues.

PMID- 11995020
TI  - North Carolina Nurses Association. Position Paper on registered nurse education
      in the 21st century.

PMID- 11995021
TI  - ANA suggests changes in Medicare.

PMID- 11995023
TI  - The changes in rules and regs are now effective!

PMID- 11995022
TI  - North Carolina Committee to Defend Health Care.

PMID- 11995024
TI  - North Carolina Nurses Association. Position statement on latex sensitivity.

PMID- 11995025
TI  - NCNA's struggle with political activism.

PMID- 11995026
TI  - Students express concern that public does not understand what nurses do.

PMID- 11995027
TI  - Diane Evans delivers message to summit-goers: there's no such thing as 'just an
      ordinary nurse'!

PMID- 11995028
TI  - Children's health insurance plan approved by HCFA.

PMID- 11995029
TI  - Mutual recognition of nursing licenses on the horizon for Mississippi RNs.

PMID- 11995030
TI  - Modern surgical technique for thyroidectomy.
AB  - Extracapsular lobectomy or total thyroidectomy are the surgical techniques
      normally used to deal with either benign or malignant thyroid diseases needing
      surgery. Both the well-known pathogenesis of benign surgical pathology and the
      positive role of post-operative radiometabolic treatment for differentiated
      carcinomas justify this surgical approach. Of course a complete understanding of
      anatomic structures and skilled operative techniques are necessary. The thyroid's
      parenchyma preventive extracapsular devascularization allows a strictly bloodless
      operative field, which makes it easier to preserve both the superior and inferior
      laryngeal nerves and the parathyroid glands of both sides. Therefore this
      procedure can be primarily considered a "vascular" technique. Our surgical
      technique is thoroughly described here, stressing anatomical landmarks and
      surgical steps, and maintaining awareness of pathophysiological implications and
      related operative choices.

PMID- 11995031
TI  - [Non-Hodgkin's lymphoma, renal carcinoma, and meningioma. A clinical case].
AB  - Some second malignant neoplasms are increasingly being observed following NHL and
      a considerable amount of data has accumulated in the literature. The authors
      describe a case of 65-year old male who presented with submandibular adenopathy.
      Results of a biopsy of the mass surgically removed revealed low grade non-Hodgkin
      lymphoma. During the staging workup, a meningioma and a renal cell adenocarcinoma
      (RCC) were unexpectedly discovered and successively resected. The patient is
      currently alive with no evidence of metastatic diseases 12 months after diagnosis
      of non-Hodgkin's lymphoma (NHL), 10 months after meningioma resection and 8
      months after RCC resection. The possibility of an underlying pathologic mechanism
      predisposing to multiple tumours should be considered. RCC and central nervous
      system (CNS) neoplasms are among second malignancies with higher incidences in
      non-Hodgkin lymphoma patients whereas with specific regard to meningioma, one of
      the most common benign intracranial tumours that sometimes shows biological
      aggressiveness and malignancy, we have currently no data in the literature.
      Increased risks for several malignancies occur late in the NHL follow-up period
      and are largely confined to patients receiving either radiation therapy or
      chemotherapy. On the other hand, increased risks for renal cancer have also been
      reported at less than one year after diagnosis of NHL and are present in all
      treatment subgroups (radiation therapy, chemotherapy, other-no treatment).
      Increased risks for CNS malignant neoplasms have also been reported at less than
      one year. The authors review the pathogenic significance of this case report
      neoplasms association in the light of the various explicative hypothesis of this
      concurrence. Possible immune mechanisms associated with these neoplasm are
      particularly pointed up.

PMID- 11995032
TI  - [Splenic epidermoid cyst. Clinical case and review of the literature].
AB  - The occasional discovery of an epidermoid cyst of the spleen, rare kind of
      lesion, in a 25 years old man who underwent a US for urethral colic, permit to
      the authors a review of the literature. Treatment is individualized in a partial
      or total splenectomy.

PMID- 11995033
TI  - [Personal modification of Sattler's instruments in subfascial endoscopic
      treatment of perforating veins].
AB  - Authors describe a method of endoscopic interruption of incompetent perforating
      veins using the Sattler equipment. They insert also, through a 2 mm port, a Foley
      n. 10 Fr collect to insufflator of CO2 with continuous distension of subfascial
      space. This technique permits subfascial elimination of incompetent perforating
      veins using a minimum surgical incision site.

PMID- 11995034
TI  - TNF alpha released in the early post-operative period is influenced by
      anaesthesia.
AB  - In this study we tested for TNF alpha concentrations 45 subjects undergoing
      elective prostatectomy performed under two different anaesthetic regimens. In
      addition, given the influence of neuroendocrine axis on immunological
      homeostasis, we also determined post surgery cortisol and norepinephrine levels.
      The patients were randomly assigned to one of two groups: group 1 (no. = 24)
      received NLA general anaesthesia, whereas group 2 (no. = 21) received spinal
      analgesia. Blood samples were drawn the day before surgery (t0), at two (t1), at
      24 (t2), at 48 (t3) and 72 (t4) hours from the completion of operation. In the
      patients assigned to the general anaesthesia group an increase of circulating TNF
      alpha was detected through t1 to t4. In the spinal group TNFa values did not
      change in t1 and t2, whereas enhanced levels of the cytokine--overlapping with
      those of group 1--were observed at 48 and 72 hrs following surgery. Cortisol
      response increased in both the groups, peaking at t1 but, at this time patients
      undergoing spinal anaesthesia were found to have significantly lower circulating
      cortisol. A rise of plasma norepinephrine was observed at t1 in the general
      anaesthesia group alone. For the early TNF alpha increase, observed in group 1
      only, we hypothesize that anaesthetics, such as NLA agents, may trigger a TNF
      alpha release in vivo. Alternatively TNF alpha production may represent the
      result of the neuroendocrine response such as cortisol and norepinephrine, to the
      surgical/anaesthetic trauma which could be blocked by subarachnoid anaesthesia.
      Conversely, the late TNF alpha increase found in all the patients studied might
      be explained by postoperative infections as well as by inflammation of the
      injured tissues and/or normal wound healing.

PMID- 11995035
TI  - [The non-recurrent inferior laryngeal nerve. Surgical experience].
AB  - During the performance of 1018 thyroid operations, 1497 recurrent laryngeal
      nerves were identified and exposed. Of the 773 visualized nerves on the right
      side, 2 were found to be non recurrent (0.26%). This abnormality may represent a
      pitfall during thyroidectomy even for very experienced thyroid surgeons. We
      emphasize that the exposure and preservation of this vital structure is the
      standard of care and an essential component of routine dissection in thyroid
      surgery.

PMID- 11995036
TI  - [VATS resection of peripheral pulmonary nodules following CT-guided cytologic
      assessment].
AB  - In a thorax surgery domain the V.A.T.S. is the important new treatment for
      particular thorax diseases. authors would like to show the advantages using
      V.A.T.S. for the therapy of peripheric lung nodules, also using a CT-guided
      extemporary cytologic tipization. The CT-guided biopsy and then an extemporary
      cytologic tipization, represent the first steps for lung nodules candidated to
      the V.A.T.S. These lesions have got singular aspects: benign lesions,
      methastasts, specific and unknown lesions. In that way traditional surgery is for
      primitive lung neoplasm in order to have a certain oncologic solution and because
      it is possible to test the complication of large resection. The CT-guided
      cytologic tipization can be done by a particular kit invented from the authors: a
      flessible needle works like an anchor and is a good repair of a nodule in order
      to proceed with V.A.T.S. This method has been utilized for 45 patients with good
      results.

PMID- 11995037
TI  - [Role of CT assessment of mediastinal lymph nodes in the preoperative staging of
      T1 pulmonary carcinoma].
AB  - The utility of the preoperative staging of T1 lung cancer is controversial. This
      is due to a lower prevalence of N2 metastases in tumors of small diameter. To
      assess the prevalence of N2 metastases in such tumors and the sensitivity and
      specificity of computed tomography in mediastinal sadiation, the authors reviewed
      CT scans and pathology reports of 56 patients who had undergone surgical
      resection of a T1 lung cancer so distributed: Adenocarcinoma 20 cases,
      adenosquamous carcinoma 14, Bronchioloalveolar carcinoma 7, Undifferentiated 7,
      Carcinoid 5, Small cells carcinoma 3. Mediastinal nodal metastases were present
      in 11 patients: 6 of them were correctly detected by CT scan. Some differences in
      terms of N2 prevalence and sensitivity were noted when the T1 were divided in two
      groups of diameter greater or smaller of 2 cm. Important considerations derived
      after dividing our patients according to the histological type. The prevalence of
      N2 metastases was greater in adenocarcinoma than in adenosquamous carcinoma but
      CT sensitivity was lower in adenocarcinoma (40% Vs 100%). The authors conclude
      that the prevalence of N2 metastases is high enough to request a preoperative
      sadiation, but the utility of CT in this purpose is limited by a low sensitivity.

PMID- 11995038
TI  - Evaluation of gastric emptying with the "uncut" Roux en Y technique.
AB  - Ten patients with benign gastric or duodenal disorders were consecutively
      included in the protocol evaluation of gastric emptying after the "uncut" Roux en
      Y to prevent the Roux en Y syndrome. There were no clinical complications. Its
      performance was not more complex from a technical viewpoint, and its morbility
      could be less that in other procedures. There are 2 important objections to the
      development of this procedure. First, the gastric emptying study shows no
      difference with the traditional Roux en Y emptying. And second, a definitive
      closure of the afferent fold is not achieved with the non-cutting linear
      stapling, the endoscopic control 6 months after surgery showing repermeation of
      the fold in 80% of the patients. The use of the technique was brought to a halt
      for its results were outside the standards of the protocol.

PMID- 11995039
TI  - [Resective surgical treatment of exocrine pancreas neoplasms. Retrospective study
      of 294 cases and review of the literature].
AB  - Authors report their own experience on the treatment of pancreatic neoplasms. Two
      hundred-ninety-four patients were observed during the years 1959-95.
      Resectability rate was 18%. Fifty-three patients underwent pancreatic resection:
      22 distal pancreatectomies (41.5%), 2 total pancreatectomies (3.7%) and 29
      pancreaticoduodenectomies (54.7%) (7 PPPD). Overall morbidity rate was 15.6% with
      decrease during the years of major postoperative complications. More frequent
      complications were renal failure (4%), bleeding (1.7%) and acute pancreatitis
      (5.6%), which was absent during the 1981-95 period. Pancreatic fistula occurred
      in 5.6%, but in the years 1981-95 only one patient suffered from it (1.8%).
      During the years 1959-70 operative mortality rate after pancreatic resection was
      22.7%, during 1971-80 was 12.5% and during 1981-95 decreased to 4.3%. Patients
      with stage I tumours survived curative pancreatic resection for about 18.2
      months, compared with those with stage II and III tumours, who survived for about
      15 and 13 months, respectively. Recent studies have demonstrated a reduction in
      the morbidity and mortality of pancreatic resections and improvement in the
      actuarial 5-year survival for patients with resected ductal adenocarcinoma. In
      the presence of lymphnode metastases, pancreaticoduodenectomy offers good
      palliation and meaningful survival. In the absence of lymphnode metastases,
      pancreaticoduodenectomy offers encouraging long-term survival rates and a chance
      for cure.

PMID- 11995040
TI  - [Colonic diverticulosis complicated with perforation. Analysis of several
      prognosis variables and criteria for emergency surgery].
AB  - The aim of this study was to analyse the clinical course, surgical strategy and
      results in patients with perforated large bowel diverticulitis. Over a 15-year
      period ending in January 1997, 25 patients (13 males and 12 females; mean age
      64.1 years) underwent operation for perforation of acute diverticulitis.
      Depending on the symptoms, the spreading of the peritonitis and the patient
      general state, different surgical techniques were performed: primary resection
      and anastomosis with and without defunctioning colostomy (5), primary left
      hemicolectomy (1), Hartmann's resection (13), Mikulicz's procedure (4), suture
      and drainage with diverting colostomy (2). The overall mortality was 16%, while
      morbidity rate was 44%; these results were strictly related to the severity of
      clinical manifestations and peritoneal contamination. Therefore it must be
      stressed that a good surgical timing is essential. Our experience and literature
      data show that primary resection and anastomosis with and without colostomy have
      good results when the patient is fit, the sepsis is localized and satisfactory
      bowel preparation is achievable. By contrast, purulent and faecal peritonitis are
      still usually best treated by Hartamnn's procedure. Finally, it is submitted to
      surgeons's experience to choose, at any situation, the best procedure regarding
      age and general state, local findings and extent of peritonitis.

PMID- 11995041
TI  - [Role of adjuvant radiotherapy in the treatment of rectal carcinoma].
AB  - Radiotherapy (RT) either pre or postoperative is widely accepted as the standard
      adjuvant treatment in rectal carcinoma invading the perirectal tissues. The main
      effect of RT was to decrease the incidence of local recurrence by 30%-50%; there
      was however no evidence of any impact on survival. With preoperative RT a large
      range of doses was tested; a dose of 35 Gy or more with fractions of 1.8-2.0 Gy
      five times per week (or a biologically equivalent regimen) is required to affect
      the local recurrence rate; with postoperative RT a more uniform dose of 45-50 Gy
      in 5 five weeks was used. Wether RT is better to be given pre or postoperatively
      has been the object of a continuing debate. The preoperative option seems at
      present preferable: the main advantages of this option are the lower morbidity
      and the possible increase of sphincter saving surgery; the availability of the
      intrarectal imaging modalities made the clinical staging very reliable,
      eliminating the major concern of preoperative RT represented by the possible
      overtreatment of early intraparietal tumours. For tumours located in the range of
      applicability of intrarectal US or MR (extraperitoneal rectum) preoperative RT
      should be considered the first choice adjuvant treatment. For tumours located in
      the intraperitoneal part of the rectum postoperative RT, on the basis of
      pathological staging, is probably preferable. Two randomized trials reported an
      improvement of the overall survival when postoperative RT was given concomitantly
      with 5 Fluorouracil but at the expense of a higher morbidity and a lower
      compliance. The most promising approach to be explored seems therefore the
      concomitant combination of preoperative RT and 5 Fluorouracil. Future studies
      should also define the more effective modality of this combination and wether 5
      Fluorouracil has to be given alone or combined with other drugs.

PMID- 11995042
TI  - [The Hartmann procedure in colorectal emergencies. Report of 76 cases].
AB  - The Hartmann procedure has, in emergency colo-rectal surgery, many implications.
      The decision is based on clinical, radiological, instrumental and pathological
      findings. The authors report the results of 76 Hartmann's procedures performed
      between 1986 and 1995 and compare their results with those found in the current
      medical literature on the topic. In particular, they draw attention to an
      increased use of this procedures in colo-rectal emergencies; the morbility and
      mortality rates confirm the severity of the clinical cases that can be treated
      with this operation. To improve results the authors propose a therapeutic plan
      that uses a score for stratification of the risk (MPI, APA-CHE II, SSI, Hinchey);
      so the surgeon can choose the best surgical operation. Finally, the authors
      underline the importance of the principles of oncology surgery in colo-rectal
      cancer.

PMID- 11995043
TI  - [Reconversion after Hartmann's procedure. Our experience].
AB  - An increasing number of intestinal reconversion after Hartmann have been
      performed in recent years, especially due to improved surgical techniques and
      progressively lengthened lifespan. The authors report 33 cases of intestinal
      recanalization of 100 interventions according to Hartmann from 1984 to 1996 (21
      not neoplastic pathologies, 12 neoplasias). The variables considered included:
      patient age, type of disease requiring intervention according to Hartmann,
      oncologic characteristic of patients with neoplasia, interval between the two
      interventions, preoperative examinations performed, morbidity and mortality after
      reconversion. Furthermore, the fundamental indications for reconversion are
      described, in particular in patients with neoplasias (CEA, transanal echo, total
      body Ct, anal manometry). The low frequency of preoperative complications, zero
      mortality, satisfactory long-term follow-up (only one patient with neoplastic
      relapse) indicate that colon-rectal reconversion can also be performed in the
      elderly and patients with neoplasias with favorable prognosis.

PMID- 11995044
TI  - Intestinal occlusion secondary to Morgagni-Larrey's herniation in an adult. Case
      report and analysis of the literature.
AB  - Morgagni-Larrey's hernias are congenital diaphragmatic hernias, rarely observed
      and generally identified accidentally due to the lack of symptoms. The authors
      report a case of intestinal occlusion secondary to Morgagni-Larrey herniation in
      an adult recently observed and underline the aetiopathogenic aspects, the
      diagnostic tools and the clinical pattern. They suggest to consider surgical
      repair as a choice of treatment, also for asymptomatic patients.

PMID- 11995045
TI  - Special session, 1999: Hurricane Floyd Recovery Act of 1999.

PMID- 11995046
TI  - North Carolina Center for Nursing releases trends study.

PMID- 11995047
TI  - Nurses and physicians speak out on health plans.

PMID- 11995048
TI  - Health records confidentiality.

PMID- 11995049
TI  - Joint statement on pain management in life care.

PMID- 11995050
TI  - Suspect older adult abuse and/or neglect?

PMID- 11995051
TI  - Nurses' deviation not the cause of fetal death.

PMID- 11995052
TI  - CRNA 99% at fault in pt. death: comparative negligence. Case on Point: Schmidt v.
      Shearer, 95 P. 2d 381 - KS (1999).

PMID- 11995053
TI  - NY: nurse 'microwaves washcloth' for infant: nurse is liable for second degree
      burns.

PMID- 11995054
TI  - NY: Dr. orders R.N. to lift obese patient: is Dr. liable for injuries incurred by
      R.N.?

PMID- 11995055
TI  - Can physicians testify as experts Re nursing standards? Case on point: Hall v.
      Sacred Heart medical Center, 988 P.2d 621 - WA (2000).

PMID- 11995056
TI  - How often should nurses monitor mental patients?

PMID- 11995057
TI  - Fetal strips "missing": did nurses monitor patient?

PMID- 11995058
TI  - TX: forceps delivery--'ping-pong' depression: alleged failure to train &
      supervise nurses.

PMID- 11995059
TI  - NY: patient stopped breathing in surgery: is "nobody was paying attention"
      admissible?

PMID- 11995060
TI  - RNs accused of negligence: must panel interview Pt.? Case on point: Gerber v.
      Juneau Bartlett Memorial Hospital, 2000 W. 641057 - AK (2000).

PMID- 11995061
TI  - [Oncologic diagnosis are still the greatest stress for patients. What goes on
      inside the patient when the diagnosis is "cancer"].

PMID- 11995062
TI  - [Nursing care planning in a child with neuroblastoma].

PMID- 11995063
TI  - [Nursing and midwifery for Health 21--control of non-transmissible diseases].

PMID- 11995064
TI  - [Graduate education in oncological nursing in Austria].

PMID- 11995065
TI  - [Model of patient transition nursing at the Linz General Hospital].

PMID- 11995066
TI  - Nurse's hearsay testimony re sexual assault is admissible.

PMID- 11995067
TI  - Dr.'s orders to nurses 'bizarre': privileges revoked. Case on point: Davenport v.
      Northeast Georgia Medical Center, 2000 WL 1693746 S.E.2d-GA.

PMID- 11995068
TI  - NY: patient attacks nurse with broken plexiglass: accidental disability
      retirement benefits denied.

PMID- 11995069
TI  - DE: nurse finds cocaine in child's diaper: father convicted of cocaine
      possession, etc.

PMID- 11995070
TI  - Suicidal patient's bathroom door 'unlocked': suicide results. Case on point:
      Wuest v. McKennan Hospital, 619 N.W.2d 682-SD (2000).

PMID- 11995071
TI  - $5 million jury verdict: fault apportioned 57% Dr. 43% RN.

PMID- 11995072
TI  - Expert sets high standards for nurses in delivery death case. Case on point:
      McGrath v. Baylor University Medical Center, 2000 WL1222039 S.W.3d-TX.

PMID- 11995073
TI  - TX: sexual assault nurse expert (SANE) testifies: SANE's testimony in criminal
      case held admissible.

PMID- 11995074
TI  - MA: nurse is deemed 'unacceptable safety risk': terminated employee sues hospital
      under ADA.

PMID- 11995075
TI  - Are nurse managers' personal records of falls privileged? Case on point: State ex
      rel Amisub, Inc. v. Buckley, 618 N.W.2d 684-NE (2000).

PMID- 11995076
TI  - "The miracle baby".

PMID- 11995077
TI  - Florida Board of Nursing Disciplinary Statistics highlight risks for Florida
      nurses.

PMID- 11995080
TI  - Stress in the workplace.

PMID- 11995081
TI  - Is your hospital hazardous to your health?

PMID- 11995082
TI  - 'Equitable contribution' doctrine does not apply to RN's insurer. Case on point:
      Am. Continental Ins. Co. v. Am. Casualty Co., 103 Cal. Rptr. 2d 63-CA (2001).

PMID- 11995083
TI  - MN: terminated RN sues hospital under ADA: 'res judicata' & 'claim preclusion'
      not applicable.

PMID- 11995084
TI  - MO: ALJ rules RN not eligible for SS disability: AIJ 'failure to consult
      vocational expert' not fatal.

PMID- 11995085
TI  - Did hospital promote nurse to facilitate termination? Case on point: Johnson v.
      Metro. Gov. for Nashville/Davidson Cty., 2001 WL 109382 SO.2d-TN.

PMID- 11995086
TI  - Health care big winner in legislative session.

PMID- 11995087
TI  - [Not yet established everywhere, already questioned in some areas: collegial
      guidance].

PMID- 11995088
TI  - [Current pain therapy].

PMID- 11995089
TI  - [Organization versus chaos in the hospital].

PMID- 11995090
TI  - [Nursing and public health within the scope of European Union integration].

PMID- 11995091
TI  - [Honorary responsibility in hospice and hospital].

PMID- 11995092
TI  - [While earlier the emphasis was almost exclusively on the "physician-patient
      relationship", today the predominant topic in health care is: trends and
      developments].

PMID- 11995093
TI  - [Protecting humans--a moral challenge].

PMID- 11995094
TI  - [The history of nursing care in the current Czech Republic].

PMID- 11995095
TI  - [Palliative care--terminal care].

PMID- 11995096
TI  - 'Whistleblower' fired for reporting Medicare fraud.

PMID- 11995097
TI  - Would reasonably prudent RN restrain or not? Case on point: Tousignant v. St.
      Louis County, 602 N.W. 2d 882 - MN (1999).

PMID- 11995098
TI  - PA: nurse assistant sues hospital under ADA: reasonable accommodation issue--no
      liability.

PMID- 11995099
TI  - OH: patient alleges defects in hip prosthesis: absence of expert testimony--no
      nurse liability.

PMID- 11995100
TI  - When nurses see 'necessary transfer' is not made. Case on point: Gladney v.
      Sneed, 742 So.2d 642 -LA (1999).

PMID- 11995101
TI  - Nurses blow whistle at phony 'trauma evaluations'.

PMID- 11995102
TI  - RN sues for retaliatory discharge under ADA. Case on point: Hamner v. Community
      Hospitals of Indiana, Inc., 92 F. Supp. 2d 803 (2000).

PMID- 11995103
TI  - OH: meds refused-threat to hit or kill LPN: conviction for assault of nurse
      affirmed.

PMID- 11995104
TI  - NY: failure to 'understand'--Pt. overdoses: do your pts. 'understand' you? Are
      you sure?

PMID- 11995105
TI  - 'Nurse of death' kills patients at VA Hospital: US. liable. Case on point: Havrum
      v. United States of America, 204 F.3d 815 (2000).

PMID- 11995106
TI  - Court cannot order nurses to practice illegally.

PMID- 11995107
TI  - Did hosp. violate FMLA: is RN guilty of job abandonment? Case on point: Stekloff
      v. St. John's Mercy Health Systems, 2000 WL 959613 F.3d-MO (2000).

PMID- 11995108
TI  - CA: Dr. uses sexually offensive language: federal courts deny EEOC complaint.

PMID- 11995109
TI  - WV: were meds mixed and injected improperly? Jury verdict for RN, MD and
      hospital.

PMID- 11995110
TI  - Must you follow Dr.'s verbal order to transfer Pt.? Case on point: Dishman v.
      Joseph, 14 S.W.3d 709-MO (2000).

PMID- 11995111
TI  - Cross exam opens door to 'other acts'.

PMID- 11995112
TI  - Are Drs. responsible for negligence of CRNAs? Case on point: Glassman v.
      Costello, 986 P.2d 1050-KS (1999).

PMID- 11995113
TI  - NC: nurse in auto accident--death results: is personnel agency liable for RN's
      negligence?

PMID- 11995114
TI  - LA: Pt. claims nurse botches venipuncture: how many chances do you get to 'stick'
      Pt.?

PMID- 11995115
TI  - Hotline called re 'abuse': retaliatory termination. Case on point: Scott v.
      Sunrise Healthcare Corp., 193 F.3d 938-IL (1999).

PMID- 11995116
TI  - Nurses demonstrate they can "just do it!".

PMID- 11995117
TI  - Remembrances of hurricane Floyd.

PMID- 11995118
TI  - Trauma care system regulations now in effect.

PMID- 11995119
TI  - Nurses extubate patient without Dr.'s order--death results.

PMID- 11995120
TI  - Nursing notes are worth their weight in gold. Case on point: Welch v. Epstein,
      2000 WL 1056052-SC (2000).

PMID- 11995121
TI  - NJ: RN accused of diverting & using morphine: suit for libel and defamation
      dismissed.

PMID- 11995122
TI  - LA: amputee's stump strikes metal bed frame: additional surgery required-
      limitations.

PMID- 11995123
TI  - Nurses should know the requirements for witnessing patients' wills. Case on
      points: in re Succession of Shamsie, 759 So.2d 329- LA (2000).

PMID- 11995124
TI  - Nurses make a difference.

PMID- 11995125
TI  - Hospital risk management and incident reporting. The duty and effect of self
      reporting.

PMID- 11995126
TI  - Forensic nursing in action. Nursing diagnosis in alleged sexual abuse of
      children.

PMID- 11995127
TI  - Are we ready for genetics?

PMID- 11995128
TI  - Professional practice advocacy.

PMID- 11995130
TI  - Living, dying, and somewhere in between.

PMID- 11995131
TI  - Nursing error: do we know it when we see it?

PMID- 11995132
TI  - Good care at the end-of-life: a report from the Florida Panel on End-of-Life
      Care.

PMID- 11995134
TI  - Making a difference in oncology nursing.

PMID- 11995136
TI  - Childbirth choices in Florida: alive and well.

PMID- 11995137
TI  - Report from the End of Life Study Panel: Pain and Palliative Care Workgroup-
      focus on pain management.

PMID- 11995138
TI  - Nurse staffing and patient outcomes from one acute care setting within the
      Department of Veterans' Affairs.

PMID- 11995142
TI  - Having the ability to influence your profession.

PMID- 11995143
TI  - Florida's nursing future as it affects the Negro nurse.

PMID- 11995144
TI  - Fifty years of racial integration in the Florida Nurses Association--a lesson in
      making social and health care policy.

PMID- 11995145
TI  - Some ethical concepts in the practice of nursing: patients' rights.

PMID- 11995146
TI  - Making a difference in orthopedics.

PMID- 11995147
TI  - Nursing from the "heart".

PMID- 11995148
TI  - Characteristics and prescriptive activities of advanced registered nurse
      practitioners in Florida.

PMID- 11995149
TI  - Professional practice advocacy.

PMID- 11995150
TI  - Accepting the leadership challenge in nursing.

PMID- 11995151
TI  - Delegation for the novice nurse.

PMID- 11995152
TI  - Students learning from nurses.

PMID- 11995153
TI  - Making a difference close to home.

PMID- 11995154
TI  - "Alleged perpetrator" of neglect--a classification to avoid.

PMID- 11995155
TI  - Seeking aging solutions.

PMID- 11995158
TI  - Ten things I wish someone had told me as a new graduate.

PMID- 11995157
TI  - Osteoporosis awareness.

PMID- 11995159
TI  - Liability for the acts of others.

PMID- 11995160
TI  - "Patients' bill of rights".

PMID- 11995162
TI  - History of the Florida State Nurses' Association.

PMID- 11995163
TI  - Making a difference in oncology.

PMID- 11995164
TI  - Nursing liability risk--three perspectives.
AB  - A number of legal issues are raised by the above hypothetical. Only a few were
      briefly discussed herein. Not addressed were the employment law issues, corporate
      negligence issues and other similar topics possibly related to the fictional
      situation.

PMID- 11995165
TI  - Forensic nursing in action: physical assessment of child abuse.

PMID- 11995166
TI  - Immunization strategies within managed care.

PMID- 11995167
TI  - Institute of Medicine report: to err is human: building a safer health care
      system.

PMID- 11995168
TI  - FNA's professional practice advocacy program.

PMID- 11995169
TI  - Color therapy.

PMID- 11995170
TI  - Nurse's failure to call for physician or supervisor.

PMID- 11995171
TI  - Board attempts to sanction administrator for acts of nurses. Case on point: Tryon
      v. Colorado State Bd. of Nursing, 989 P.2d 216 - CO (1999).

PMID- 11995172
TI  - KY: ER nurse hears Pt.'s 'dying declaration': is nurse's testimony admissible in
      evidence?

PMID- 11995173
TI  - MS: nurse practitioner's affidavit barred: nurse expert's testimony held
      inadmissible.

PMID- 11995174
TI  - 'Bed sores' were the cause of a patient's death. Case on point : Parson v.
      Interfaith medical Center, 700 N.Y.S. 2d 224- NY (1999).

PMID- 11995175
TI  - Impact of balanced budget act (BBA) of 1997 on health care.

PMID- 11995176
TI  - Is quality education your bag?

PMID- 11995177
TI  - Summary of the barriers to practice survey.

PMID- 11995178
TI  - NCHA surveys North Carolina nursing shortage.

PMID- 11995179
TI  - Nursing's opportunities in end-of-life care.

PMID- 11995180
TI  - The benefits of an electronic patient record.

PMID- 11995181
TI  - Unionization--why IUOE, why now? One perspective on the unionization of Duke
      nurses.

PMID- 11995182
TI  - Professional practice advocacy forums gather workplace information.

PMID- 11995183
TI  - [Hepatitis B in children: natural history and therapy].
AB  - Children with chronic hepatitis B, face life long disease and complications of
      cirrhosis and hepatocarcinoma. Naturally, it is estimated that half to two third
      of the children will clear the hepatitis Be antigen during childhood. Treatments
      aim to increase the HBe Ag to Ab seroconversion rate, which may also favour the
      loss of HBs antigen, ultimate goal. Interferon alpha was the first approved
      treatment for pediatric chronic hepatitis B, and was shown to increase the HBe ag
      loss from 11% in control group to 26% in treated patients (5 MU/square meter body
      surface area for six months) at one year, and 33% at 18 months. Side effects
      include mainly fever, flu like symptoms, and growth impairment during the
      treatment phase. Nucleotide analogues have now emerged as a promising alternative
      to treat chronic hepatitis B. The optimal dose for children is established to 3
      mg/kg once daily up to 12 years old. Efficacy trials show complete virologic
      response in 23% of all treated patients after one year, as compared to 13% in the
      placebo group, and in 34% of patients with basal transaminases above two times
      upper limit of normal; versus 16% in controls. Lamivudine inhibits viral DNA
      which favours cellular immune response. Lamivudine resistance due to variant
      viruses is observed in 19% of children after one year. Other nucleotide
      analogues, such as entecavir and adefovir will soon be tested in children, and
      combination with Lamivudine may improve results. Finally, vaccine technology is
      being tested in adults, to induce a cellular immune response towards hepatitis B
      antigens, but no clinical benefit has so far been established.

PMID- 11995184
TI  - [The face, the mask and the times. Natural history of the segmental architecture
      of the face].
AB  - Extending from the supra-occipital region down to both clavicles, the face is an
      original anatomical entity which constituTes the main field of interaction
      between the brain and the external world. We here demonstrate that essential
      structures arise from the neural crest cells and that the segmental migratory
      pathway of these cells leads to the segmental ontogenesis of the head, and of the
      anterior neck area from seven distinct morphogenetic units which enjoy each of an
      independEnt growth potential. In the adult, the neural and segmental origin of
      the face is temporarily masked by the superficial musculoaponevrotic system which
      supports its cutaneous cover. Nevertheless, this fundamental architecture appears
      fugitively in the mimics of facial expression, then more obviously in the ptotic
      and folding phenomenons involved in cephalic skin ageing.

PMID- 11995185
TI  - [Development of surgical treatment of primitive and metastatic rectal cancer].
AB  - There are many ways by which the surgeon can optimize curative resection for
      rectal cancer. Appropriate margins with total mesorectal excision, should be the
      goals for tumors in the lower two-thirds of the rectum. Reconstruction should be
      performed, whenever technically possible, by a colonic J-pouch. Preservation of
      pelvic autonomic nerves is possible in most cases, reducing the risk of
      postoperative sexual and urinary dysfunction. New techniques increase the
      frequency of curative treatments of metastatic disease. Towards either the
      primary or the metastatic disease, the new therapeutic strategies offer an hope
      of cure, and a better quality of life, to an increasing number of patients.

PMID- 11995186
TI  - [Bone grafts using tissue engineering].
AB  - An overview of bone grafts and, in particular, the allografts is presented. The
      availability of bone allografts, has promoted their use at the expense of the
      autograft. However, the loss of the cellular activity in an allograft, makes them
      less performant than an autograft. The use of an allograft in a small size defect
      can be advocated provided that the implantation technique is stringent. In case
      of a large segmental bone defect, an allograft can be considered whereas an
      autograft is not anymore possible. A massive bone allograft allows an anatomical
      reconstruction and the preservation of strong tendon insertions. In tumor
      surgery, a bone allograft has become one of the best options to reshape the
      skeleton. To offset the poor remodeling of the massive bone allografts, and to
      improve the take of small size bone allografts, researches are presently carried
      on, using tissue engineering in order to recover a cellular population. The aim
      is to combine an acellular bone graft with the cells of the recipient. Cells are
      procured from the bone marrow. Stromal cells are isolated, cultured, so that they
      will grow with an osteoblastic phenotype. They can be used alone or in
      association with a bone graft. It is believed that tomorrow such cellular therapy
      will become a routine procedure.

PMID- 11995187
TI  - Nurse-expert's opinion inadmissible re 'cause of death'.

PMID- 11995188
TI  - 'Missing' EKG strips: spoliation of evidence? Case on point: Magette v. Goodman,
      2001 WL 218981 A.2d-PA.

PMID- 11995189
TI  - MN: did new injection product cause injury?: Products liability & nurse
      negligence claim denied.

PMID- 11995190
TI  - PA: nurse has severe allergy to latex gloves: products liability suit--warranty
      limitations issue.

PMID- 11995191
TI  - Failures to follow hospital policies result in patient's death. Case on point:
      Whittington v. Episcopal Hospital, 2001 WL 114942 A.2d-PA.

PMID- 11995192
TI  - The CAM movement and the integration of quality health care: the case of
      chiropractic.
AB  - High and increasing consumer demand for complementary and alternative medicine
      (CAM) services necessitates a concerted focus to determine the effectiveness of
      such practices and to ensure that future possible integration of CAM with
      conventional medicine is founded on sound evidence-based principles of quality
      health care delivery. The example of chiropractic provides useful insights to
      guide further research and integration of evidence-based CAM into mainstream
      health care in the United States. A critical point of departure for this area of
      inquiry is identifying and addressing barriers to conducting scientifically sound
      and meaningful cross-disciplinary, practice-based research.

PMID- 11995193
TI  - Organizational and provider characteristics fostering smoking cessation practice
      guideline adherence: an empirical look.
AB  - We examined the relationship between physician adherence with a smoking cessation
      guideline and organizational structures, policies, leadership support, and
      physician knowledge and attitudes. A random sample of 844 physicians practicing
      in 127 VHA hospitals was surveyed. Survey results were aggregated to the hospital
      level and linked with data on organizational characteristics from the 1998 annual
      survey of hospitals by the American Hospital Association. Significant predictors
      of adherence included organizational policies related to nicotine replacement
      prescriptions, the timing and effectiveness of guideline implementation,
      physicians' knowledge of VHA clinical guidelines generally, and physicians'
      beliefs about the receptiveness of patients to smoking cessation.

PMID- 11995194
TI  - CAHPS in practice: the Iowa demonstration.
AB  - This article evaluates the usefulness of the Consumer Assessment of Health Plan
      Study (CAHPS) surveys and reports in a demonstration and evaluation with three
      health care purchasers in Iowa. The CAHPS survey detected significant differences
      between health plans in several domains of health care. Both paper- and Web-based
      consumer reports were developed and distributed to consumers and stakeholders.
      There was some agreement on the value of these reports, but areas for improvement
      were noted.

PMID- 11995195
TI  - Improving the quality of occupational health care in Washington State: new
      approaches to designing community-based health care systems.
AB  - The need for concerted action to improve quality was stressed in the recent
      Institute of Medicine report, Crossing the Quality Chasm: A New Health Care
      System for the 21st Century. This article describes an innovative community-based
      delivery system initiative designed to improve quality and health outcomes for
      occupational health conditions. Known as the Occupational Health Services (OHS)
      project, this Washington State initiative focuses on three targeted conditions:
      low back sprain, carpal tunnel syndrome, and fractures. To fulfill its purpose,
      which is to provide clinical resources and training opportunities and foster
      quality improvement activities on a community-wide basis, the OHS incorporates
      several key delivery system components, including systems to track patient and
      employer satisfaction and health outcomes; formal physician agreements that will
      provide incentives for using best-practices; and community-based Centers of
      Occupational Health and Education (COHEs) that will function as a resource for
      providers, patients, and employers. Our experience in developing the OHS quality
      improvement initiative should have relevance for health care clinicians,
      administrators, policy makers, and researchers engaged in similar pursuits
      outside the field of occupational health.

PMID- 11995196
TI  - Providers of primary care to homeless women in Los Angeles County.
AB  - Little is known about the access barriers homeless women face at the sites where
      they are most likely to receive primary health care. To investigate this issue,
      we administered a mail survey to administrators and clinicians at clinic sites
      that were actual or potential providers of primary health care to homeless women
      in Los Angeles County in 1997. The response rate was 65%. Ninety percent of the
      homeless women seen by responding sites were seen at only 34% of those sites
      (designated as "major providers"). Deficiencies were identified in several
      structural and process characteristics that enhance access to and quality of care
      for homeless women, including clinician training in care for homeless persons;
      formal screening for homeless status and associated risk factors; and on-site
      provision of comprehensive health services, including mental health, substance
      abuse, reproductive health, and ancillary services. Some, but not all,
      deficiencies were less severe at major providers. Our results suggest that,
      although providers of care to homeless women share challenges faced by many
      safety net providers, there are several policy interventions that could improve
      access to and quality of care for homeless women.

PMID- 11995197
TI  - Leadership in health care and the leadership literature.
AB  - Crossing the Quality Chasm, the Institute of Medicine's recently issued report on
      the quality of health care in America, is a call to arms for the urgent redesign
      of the U.S. health care system. The big question confronting health care
      organizations is how to mount new strategies that will enhance organizational
      effectiveness and reduce system failures as well as individual errors. Redesign
      implies organizational restructuring and engineering as well as serious steps in
      organizational development, with the emphasis on leadership enhancement
      strategies focused on performance excellence. This article addresses the state of
      the leadership literature and concludes that massive new investments will have to
      be made to tackle the issues of leadership training and accountability.

PMID- 11995198
TI  - Women's health and human rights in Afghanistan: continuing challenges.
AB  - Physicians for Human Rights has released a ground-breaking survey of more than
      1,000 Afghan women and men on their attitudes and experiences regarding health
      and human rights for Afghan women. Health care for women in Afghanistan still
      poses daunting challenges.

PMID- 11995199
TI  - How do you know that your care is improving? Part II: Using control charts to
      learn from your data.
AB  - This article builds on my article in the January 2002 issue of JACM on the use of
      run charts to analyze data variation and document process improvement. It
      describes a more powerful tool than the run chart for analyzing variation and
      measuring process improvement, namely, the control chart developed by Walter
      Shewhart. This article first explains the basic elements of a control chart, the
      tests for detecting a special cause variation, and how to choose the best control
      chart for the type of data being collected. It concludes with one case study
      using a control chart to document a successful intervention and some suggestions
      regarding computer software.

PMID- 11995200
TI  - [The dry skull model in orthodontics].
AB  - Orthodontic therapy aims to displace teeth by means of orthodontic appliances.
      Forces, applied on the teeth, induce remodeling of the alveolar process in upper
      and lower jaw resulting in a new position of the teeth into both jaws. In this
      publication an attempt has been made to test a model (dry skull model) which
      could provide a better understanding of the effect of force application on tooth
      and bone displacement. Initial tooth displacement (microscopical), right after
      force application, could give an indication for the longitudinal tooth
      displacement to be expected. Variables as the point of force application, the
      amount and direction of the force and the localisation of the centre of
      resistance are determining factors for the final tooth displacement. This study
      attempts to forecast the longitudinal tooth displacement by evaluating the
      initial displacement on the dry skull. Initial tooth displacement has been
      measured by means of laser measuring techniques (holography, speckle
      interferometry and laser reflection technique). These techniques are non-invasive
      (non-destructive testing) and permit the measurement of small tooth and bone
      displacements varying between 0.5 and 15 microns. According to the results of the
      animal studies, it became obvious that initial tooth and bone displacements are
      indicative for the longitudinal effect of the same sort of force application on a
      short time basis (5 to 8 weeks). The final conclusion is that initial tooth
      displacement measured on a dry skull has a predictive value for the longitudinal
      effect of orthodontic force application. Moreover, the creation of a finite
      element model looks very promising in this respect. More research is needed to
      test the finite element model further and to make it useful for testing the
      effect of force application on skull and tooth structures of a patient.

PMID- 11995201
TI  - [The importance of correct policy options for oncologic patient care].
AB  - During recent years, a growing number of papers have been published, showing how
      the treatment of malignant disease can meet, in various centres, with varying
      degrees of success. Doubtlessly, many more such papers would reach the journals
      hut for the lack of reliable follow-up data concerning survival, staging, type of
      treatment, selection criteria, etc. This article summarizes some data of 7
      examples derived from observations in continental Europe, the UK, Canada and the
      US. Their most remarkable feature are the far from negligible differences in
      outcome (either in survival or in related "administrative" parametres such as
      treatment waiting time). Most of these studies stress the importance for
      oncologic patient care, of factors that are not directly related to primary
      clinical and/or scientific competence, but to policy and management aspects of
      the problem such as: providing adequate staff and technical infrastructure,
      creating cooperative networks and, last hut not least, organizing possibilities
      to collect, as widely as possible, enough data allowing a reliable appraisal of
      what has, or has not, been achieved.

PMID- 11995202
TI  - Towards an endoscopic intra-uterine treatment for congenital diaphragmatic
      hernia.
AB  - Congenital Diaphragmatic Hernia (CDH) is a simple defect in the diaphragm that
      however can lead to severe or lethal pulmonary hypoplasia. Fetuses with their
      liver herniating into the thorax and with a small lung volume as reflected by a
      lung-to-head ratio below < 1.0, have virtually no chance to survive despite most
      modern postnatal care. They are therefore theoretical candidates for in utero
      therapy. There is a large experimental basis supporting tracheal occlusion (TO)
      as a method to trigger lung growth, although the optimal time and duration of TO
      remains to be defined in humans. Animal studies have also shown that TO can be
      performed completely endoscopically, by means of in utero tracheoscopy and
      endoluminal balloon placement. TO was therefore applied by leading fetal surgery
      centers. Initial results with tracheal clipping via hysterotomy were
      discouraging, but more recently fetoscopic clipping was associated with a nearly
      70% survival. The time has now come to achieve TO by means of percutaneous
      fetoscopic balloon plugging. This will make the intervention more acceptable in a
      European setting, where open fetal surgery never took off.

PMID- 11995203
TI  - [1,25-dihydroxyvitamin D3: the endocrine system meets the immune system].
AB  - 1,25(OH)2D3, the activated form of vitamin D, is well known for its effects on
      calcium and bone metabolism, but also non-classical effects on cells of the
      immune system were described, in vivo as well as in vitro. Structural analogues
      have been developed with less calcemic effects, but at least comparable immune
      effects. Our group showed that treatment with 1,25(OH)2D3 can protect the NOD
      mouse, the murine model for type 1 diabetes, from diabetes in primary, secondary
      and tertiary prevention. This effect is based on shifts in cytokine profiles
      (Thelper1 to Thelper2), that occur specifically for the autoantigens, and on
      enhanced sensitivity of the autoreactive T lymphocytes to apoptotic signals thus
      leading to a better elimination of these potentially dangerous cells. 1,25(OH)2D3
      and its analogues can therefore be considered as interventions aimed at the
      prevention or treatment of human type 1 diabetes.

PMID- 11995204
TI  - [Convulsions during treatment of acute lymphoblastic leukemia in children].
AB  - BACKGROUND: The prevalence of seizures in children with acute lymphoblastic
      leukemia (ALL) varies between 3 and 13% depending on the various studies, whereas
      it is 1% in the general population aged under 15 years etiopathogenesis and
      outcome of seizures in children during treatment for ALL. METHODS: A
      retrospective study was carried out in 204 children with a consecutive diagnosis
      of ALL, 89 females and 115 males, aged between 5 months and 17 years and 11
      months, diagnosed between 15-4-1988 and 15-4-1998, and treated at the Division of
      Pediatric Oncology and Pediatric Hematology of Turin University using three
      successive generations of AIEOP protocols 88 (48 cases), 91 (86 cases) and 95 (70
      cases). Observation of the patients in the study ended on 30-9-1998. The criteria
      for eligibility were those stated in the respective protocols. Seizures were
      classified using the international classification; the diagnosis was made if a
      doctor, a nurse or a reliable relative witnessed the event with confirmation by
      the consultant neurologist. RESULTS: Twelve out of 204 (5.8%) patients in this
      series presented seizures: 2 out of 48 cases using protocol 88 (4.1%), 6 out of
      86 cases using protocol 91 (6.9%) and 4 out of 70 cases using protocol 95 (5.7%).
      None of the patients had critical episodes or other significant neurological
      pathologies prior to the onset of ALL, nor had they been affected by leukemic
      meningosis or undergone cranial radiotherapy. When evaluating the possible
      etiology, the authors noted that, except for one case of febrile convulsion, the
      seizures in the remaining patients could be attributed to the toxicity of
      chemotherapy. With regard to the evolution of seizures, only one patient died,
      whereas the others showed no neurologic sequelae. CONCLUSIONS: The frequency of
      seizures in children receiving treatment for ALL in the series analysed here is
      in line with that reported in the literature. Neurotoxicity caused by
      chemotherapy appears to be the main etiopathogenetic factor.

PMID- 11995205
TI  - [Food allergies in early childhood. 1. General concepts, etiopathogenesis, and
      main clinical features].
AB  - Abnormal immune reactions to food antigens are a rather common event during
      infancy. Adverse reactions to milk proteins occur in 2.5% of suckling infants.
      Both IgE and non IgE-mediated allergic mechanisms may be involved in the
      pathogenesis of food allergy. IgE mediated allergic responses are the most
      dramatic and the most often diagnosed types. Non IgE mediated food allergy is
      usually more difficult to diagnose and its clinical course is more chronic. Food
      induced allergic reactions mediate a variety of symptoms, involving the
      gastrointestinal and respiratory tract and the skin. A limited number of foods
      are responsible for the vast majority of allergic reactions: cow milk proteins,
      egg, fish and peanuts are the main causes. The vast majority of infants with
      formula-protein intolerance will outgrow their symptoms by the third year of age.
      Eliminating the food allergens is the only means of dealing with the problem. In
      part I of this series, immunopathogenic mechanisms and clinical disorders are
      described.

PMID- 11995206
TI  - [Floating-Harbor syndrome: first case in Italy associated with growth hormone
      deficiency].
AB  - The Floating-Harbor Syndrome (FHS) is a rare entity characterised by a clinical
      triad: facial dysmorphism, retarded speech development and short stature with
      delayed bone age. The case of a 9-year and 8/12 months old boy showing the
      typical features of this syndrome associated to a severe GH deficiency is
      reported. At diagnosis of FHS, the weight was 16 kg (< 3 degrees percentile),
      height 112 cm (< 3 degrees percentile), cranial circumference 53.8 cm (> 90
      degrees percentile). The evaluation of growth hormone secretion by two Insulin
      Tolerance Tests confirmed an insufficient GH peaks response (2.7 ng/ml and 4.6
      ng/ml). He had a slight mental delay (IQ: 60) involving language skills. After 1
      year of treatment with r-hGH (0.6 IU/kg/week), an increase in growth velocity (11
      cm/year) in the length (123 cm), and in body weight (20.5) has been observed.
      This case is the 22nd report with this syndrome and the first in Italy. The
      association between GH deficiency and FHS, and the beneficial effects of a
      substitutive treatment are described.

PMID- 11995207
TI  - Abdominal pain in children: a case of acalculous cholecystitis.
AB  - Acalculous cholecystitis is a rare disease in children. Most cases are associated
      with systemic infections or with autoimmune pathologies, but it may also occur
      without predisposing factors. A case observed in an otherwise healthy child is
      reported.

PMID- 11995208
TI  - [Long-term follow-up and bone imaging in acquired osteochondrodysplasia in a
      female patient with thalassemia and desferrioxamine hypersensitivity].
AB  - We report a female thalassaemia major patient who developed short stature and
      osteochondrodystrophic lesions during therapy with desferrioxamine (DFX). Healing
      was noted after the dose of DFX was decreased for 3 years. Unfortunately the
      spinal cartilage abnormalities did not change suggesting an irreversibility of
      the ossification process.

PMID- 11995209
TI  - [Endocrine glands in childhood].

PMID- 11995210
TI  - [Respiratory tract diseases].

PMID- 11995211
TI  - [Heart diseases].

PMID- 11995212
TI  - [Treatment approaches in gunshot injuries of the extremities].

PMID- 11995213
TI  - [Treatment approaches in gunshot injuries of the extremities].
AB  - In the view of efficiency and cost effectiveness the increasing incidence of
      gunshot wounds in Europe demands a modification of treatment protocols. The
      general basis are debridement of soft tissue injuries, antibiotics and fracture
      stabilization. The pathology of gunshot wounds and established treatment
      algorhithms, however have to be adjusted to the ongoing development of gun
      technology and the thereby caused specific lesions. The treatment of injuries
      caused by high velocity projectiles necessitates a proactive surgical strategy.
      Small caliber gunshot wounds can be treated more conservatively. The following
      review presents an overview on the ballistic and surgical basis for the treatment
      of gunshot wounds of the musculoskeletal system.

PMID- 11995214
TI  - [Treatment of complicated fracture of the distal radius with external fixator.
      Follow-up--complications--outcomes].
AB  - The performance of the external fixation regarding severe fractures of the distal
      radius was evaluated by means of a very detailed retrospective study. Between
      1989 and 1994 74 Patients with 76 fractures of the distal radius with a mean age
      of 69 years for female and 39 years for male patients were treated with the
      external fixator. 37% were open fractures. Using the ASIF classification, 21%
      were type A-fractures, 8% were type B-fractures and 71% were type C-fractures. In
      44 cases the external fixator was used primarily, in 32 cases secondarily after
      failed conservative treatment. Additional procedures were partially necessary (K
      wires, screws, bone grafts etc.). 32 complications had to be noted, the lesion of
      the superficial branch of the radial nerve being the most common (16%). After a
      mean follow up of 36 months 60 patients with 61 fractures could be evaluated
      clinically and radiologically. With the Sarmiento score as well as the Castaing
      score, 84% could be classified as very good or good, 16% as fair, no poor results
      were recorded. From this study we conclude that the primary treatment of complex
      fractures of the distal radius can be performed with external fixation along with
      the additional procedures necessary (K-wires etc.). Because of the reliable
      elimination of pain caused by the fracture, it forms a preventive measure against
      reflex sympathic dystrophy.

PMID- 11995215
TI  - [Supracondylar humerus fracture in childhood--an efficacy study. Results of a
      multicenter study by the Pediatric Traumatology Section of the German Society of
      Trauma Surgery--I: Epidemiology, effectiveness evaluation and classification].
AB  - In this retrospective study of the pediatric trauma group of German trauma
      society, issued to investigate the state of the art treatment of the
      supracondylar fracture of the humerus, 13 clinics took part. In this first part
      of our study we tested the epidemiology and effectivity of therapeutic
      interventions based on the classification of v. Laer. 886 fractures were included
      with an average patients age of 5.8 years (+/- 2.9). Causes of trauma was in 45%
      playing, followed by school/kindergarden and sports injuries. Fractures were
      initially classified according to v. Laer and showed following displacement:
      35.4% Type I, 21.9% Type II, 18.1% Type III and 24.6% Type IV. 10 of the 886
      cases (1.1%) were open fractures. Damages to nerves were described in 45 patients
      (5.1%) and only 7 (0.7%) had primary vessel lesions. 476 patients were treated by
      reduction of fragments, 72% using a closed technical approach and 28% using an
      open approach. 6% underwent a second resposition-maneuver, which was mainly
      observed after crossed Kirschner-wire in type-III-and-IV-fractures. Therapy was
      changed in 5.1% mostly of the cases were initially closed reduced and then fixed
      with a collar and cuff sling. 540 patients were seen at follow-up (61%). 81.1% of
      these patients showed symmetrical axis compared to the uninjured arm. A varus
      deformity was noted in 11.7%, a valgus-deformity in 7.2%. Analysis of effectivity
      showed that the primarily used classification was not sufficient for prediction
      of the outcome after reposition and retention. Therefore the classification was
      modified based on 4 groups: Type I undisplaced, Type II displacement in one
      plane, Type III displacement in two planes and Type IV displacement in three
      spatial planes. Using this classification we could found that in group II 25% of
      reduction an 7% of retentions were ineffective. For group III and IV we found
      that > 20% of the retention proofed to be ineffective.

PMID- 11995216
TI  - [Supracondylar humerus fracture in childhood--an efficacy study. Results of a
      multicenter study by the Pediatric Traumatology Section of the German Society of
      Trauma Surgery--II: Costs and effectiveness of the treatment].
AB  - The following are the results and conclusions of a retrospective research study
      done on 886 patients with supracondylar fractures of the humerus. The study
      evaluates how effective the treatment procedures of the fractures are. The
      patients' fractures were categorized into four groups. It made it easier to
      differentiate between dislocated and undislocated fractures (see part I Weinberg
      A et al.). The following parameters were established to evaluate the treatment
      procedures and to create relevancy to the final outcome depending on the degree
      of difficulty of the fractures: Length of hospitalization, amount of
      repositioning procedures (including if an open or closed procedure was needed),
      amount of post repositioning procedures and the recommended change of therapy,
      method of retention and fixation, necessary metal removal, amount of check ups
      needed. The amount of x-ray exams could not be established due to insufficient
      documentation. The study showed a rather random pattern regarding length of
      hospitalization and the amount of check ups especially among type I and II
      patients. Open versus closed repositioning procedures did not seem to be
      advantageous. The implanted wires did not prevent infections. It just increased
      the treatment procedure by another hospitalization and anesthesia to remove the
      implanted wires. Physical therapy was not necessary and was only prescribed in
      cases of prolonged immobilization. The results of this study generated
      consequences regarding treatment procedures and developed a more efficient
      treatment protocol: Type I and II (dislocated and undislocated fractures in one
      plane) will be treated conservatively on an out-patient basis. Type I in a cast.
      Type II in a blount or plaster cast with flexed angle between 100 degrees and 130
      degrees. Type III an IV (dislocated and undislocated fractures in two or three
      planes) will be treated if possible with a closed repositioning procedure.
      Otherwise a close repositioning procedure will be necessary and followed with
      some kind of KD-osteosynthese to capture the fracture. The patient will be
      hospitalized for a short period. The blount procedure will not be sufficient for
      this type of fracture. Therapy and procedure will be translated put in a
      perspective research study.

PMID- 11995217
TI  - [Treatment options in traumatic epidural hematomas].
AB  - The authors report 118 consecutive cases of patients with traumatic extradural
      hematoma (EDH) which were analyzed according to different clinical parameters and
      treatment modalities. Patients, treated for EDH between 1992 and 1998 in our
      department were distributed into 5 treatment groups depending on their clinical
      and neuroradiological findings on admission and during the hospitalization. Group
      I consisted of 75 patients (64%) who required immediate surgical evacuation of
      the hematoma after admission. Group II included 12 patients (10%) with initially
      conservative treatment despite visible EDH on the first CT-scan, which had to be
      operated on in the course because of neurological deterioration or increase of
      hematoma size. The 14 patients (12%) forming group III developed an acute EDH
      after the initial CT-scan revealed no extradural blood; 7 patients (6%) out of
      group IV showed a chronic EDH (delay trauma/diagnosis > 72 h), which required
      operative evacuation. All 10 patients (8%) comprising group V were treated
      conservatively. In each group the following parameters were analyzed: patient
      age, size and location of hematoma, trauma mechanism, additional intracranial
      lesions or skull fractures, intraoperative findings and neurostatus on admittance
      and during the hospitalization. The decision for non-operative treatment of EDH
      and the timing of a delayed intervention has to be made individually in each case
      in dependence of parameters like patient age, hematoma-size and -location and
      neurological status and course. Chronic EDH should be operated immediately, as
      well as hematomas presenting with an increase in size. Delayed developing EDH
      imply worse outcome and make adequate surveillance of high-risk patients
      mandatory.

PMID- 11995218
TI  - [Psychological trauma in trauma medicine--the current status of psychological
      management of trauma victims in Germany].
AB  - A clinically significant amount of accident victims display psychological
      disorders as a reaction to the trauma. Outcome studies on multiple trauma
      emphasize that life quality following severe accidental injury is influenced by
      early diagnosis and treatment of psychic co-morbidity. In a nationwide survey
      concerning the state of the art in in-patient treatment of injury patients
      conducted in Germany, every surgical ward was contacted and physicians were asked
      about their standard procedures of detecting and treating psychotraumatic
      complications. The results of the survey indicate that surgeons pay close
      attention to signs of psychological comorbidity and have good basic knowledge of
      psychotraumatic disorders. Nevertheless, there are structural deficiencies caused
      by the fact that only a few wards have staff specially trained in
      psychotraumatological care. Only a minority of patients is treated for
      psychotraumatic symptoms. In view of the high prevalence rates for
      psychotraumatic disorders in the aftermath of severe accidental injuries, the
      article discusses the need for psychic diagnosis and support as well as the
      necessary cooperative structures required in the model of Integrative
      Posttraumatic Acute Care.

PMID- 11995219
TI  - [Axis deviation, cartilage damage and cruciate ligament rupture--concomitant
      interventions in replacement of the anterior cruciate ligament].
AB  - BACKGROUND: Osteochondral lesions and osteoarthritis in young patients are often
      caused by chronic knee instability and varus malalignment. We present the
      indications, operative technique, and results for the combined operation of high
      tibial osteotomy and cruciate ligament reconstruction. MATERIALS AND METHODS:
      From April 1996 until December 2000, 58 patients (average age: 33 years)
      underwent simultaneous osteotomy (57 correcting valgus, 1 valgus malalignment)
      and cruciate ligament reconstruction (49 ACL, 7 PCL, 2 ACL & PCL) which was
      routinely performed with an arthroscopic technique after completion of the
      osteotomy (closed wedge technique). Average correction angle of the osteotomy was
      7 degrees (4-10 degrees) with a mean malalignment of 5 degrees (0-10 degrees).
      Thirteen patients underwent additional cartilage surgery (osteochondral autograft
      transplantation, autologous chondrocyte transplantation, microfracturing), and
      two patients were implanted with a collagen meniscus (CMI) at the same time.
      RESULTS: Preoperatively the Lysholm score was 66 (35-81) points and increased to
      81 (74-95), 87 (79-99), and 93 (88-99) points 3, 6, and 12 months after surgery,
      respectively. Subjectively all patients reported an improvement of preoperative
      swelling, pain, and instability. Additional cartilage surgery or meniscus
      implantation did not significantly alter the clinical score values. Complications
      were noted in four patients. CONCLUSIONS: Unstable knees with varus malalignment
      can be sufficiently treated by osteotomy and cruciate ligament reconstruction at
      the same time, suggesting that unicompartimental decompression and treatment of
      instability is a causal and cost-effective therapy delaying the progression of
      osteoarthritis and minimizing clinical symptoms. Performing both operations in
      one procedure facilitates early rehabilitation and the return of these patients
      to the activities of daily living and sports.

PMID- 11995220
TI  - [Endoscopically controlled stabilization of humerus shaft fractures. The
      endoscope as an aid in minimally invasive osteosynthesis].
AB  - This study describes the anatomical basis of direct visualization of the radial
      nerve and of fracture reduction in humeral shaft nailing and reports first
      clinical results. Fourteen cadavers were random selected and dissected in order
      to determine the exact course of the radial nerve in relationship to anatomical
      landmarks. In individuals with a total humeral length between 25-33 cm the radial
      nerve was found to cross the humeral shaft exactly in the middle of the long axis
      of the humeral shaft. The average distance from the lateral epicondyle to the
      point were the radial nerve penetrates the lateral intermuscular septum was 11.9
      +/- 1.0 cm, the distance from the posterior tip of the acromion to the crossing
      of the nerve with the medial border of the humeral shaft was 12.9 +/- 1.5 cm.
      Using these landmarks in six clinical cases fracture reduction, visualization of
      the radial nerve and intramedullary nailing could be achieved with endoscopic
      control. There were no surgical complications such as secondary radial nerve
      palsy, hematomas or wound healing problems. With the use of the endoscope the
      number of secondary radial nerve palsies associated with intramedullary humeral
      shaft nailing might be reduced in the future.

PMID- 11995222
TI  - [Computer-assisted screw osteosynthesis of the posterior pelvic ring. Initial
      experiences with an image reconstruction based optoelectronic navigation system].
AB  - Injuries of the posterior pelvic with combined anterior and posterior instability
      require the stabilisation of both the anterior and posterior pelvic ring. If the
      injury only involves the ligamental connections, then a transileosacral
      osteosynthesis with screws is the minimal invasive and biomechanically suitable
      method of choice. The difficulty with this approach is the correct placement of
      the screws. Their position must be monitored intraoperatively in 3 planes (inlet,
      outlet and lateral viewing). This denotes that conventional methods involve high
      radiation dosages for the patient and the surgical staff. Having the system
      readily available and being able to perform updates during the operation,
      fluoroscopically supported navigation for the treatment of fresh injuries becomes
      possible. Between October 1999 and December 2000 7 patients with traumatic
      instability of the posterior pelvic ring were treated by computer assisted
      percutaneous transileosacral screw osteosynthesis. In each case the
      osteosynthesis of the ileosacral joint was performed with two cannulated AO 7.3
      mm titanium screws. After the operation the screw position was controlled by CT
      scanning and compared to the data acquired intraoperatively. No patients had
      infection, and there were no postoperative neurological defects. The
      postoperative CT scans showed no intraspinal or intraforminal malplacement of the
      screws. In two cases a slight tangential screwthread penetration through the
      ventral sacrum was found. Our first experiences with this novel technology are
      encouraging and clearly demonstrate the advantages of fluoroscopic supported
      passive navigation systems for the optimal placement of ileosacral screws.

PMID- 11995223
TI  - [Complications, misjudgments and errors].

PMID- 11995224
TI  - [Changing a cement-free endoprosthesis of the great toe base joint].
AB  - We report about a 36 year old patient with insufficient silicone implant
      arthroplasty of the great toe. For a change of endoprothesis we successfully used
      an non-cemented modular alloarthroplasty system.

PMID- 11995225
TI  - [Iatrogenic "metalloma" (titanoma) caused by implant failure in "metal-backed"
      patellar joint surface replacement].
AB  - Patellofemoral problems frequently provide the cause for revisions after total
      knee replacements (TKR). Problems with metal-backed patellae, in particular, have
      been reported on in the past, with a failure rate of 33%. As a result of implant
      failure, there is an increase of polyethylene and metallic wear, which eventually
      leads to a synovialitis and metallosis. We report a case of a iatrogenic induced
      metallosis of the knee joint resulting from failure of a metal-backed patella
      component with the formation of a substantial pseudotumor within the popliteal
      fossa. Intraoperatively, a browny-grey, knotted and hard structure was to be
      seen, which histologically imposed as a hyalinated scar tissue with black
      particular deposits. Energy dispersive X-ray microanalysis showed a high level of
      titanium within the intra- and extracellular deposits. In differential diagnosis
      these findings were postulated as "metalloma" (titanoma). In cases of
      periprosthetic pseudotumors, particular those with implant failure, a iatrogenic
      induced metalloma should be considered.

PMID- 11995226
TI  - [Unusual removal of a Kuntscher nail after 35 years].
AB  - A 68 year old patient with persistent feeling of sickness and increasing pain in
      the left forearm was seen. A complex both bone fracture of the distal forearm
      shaft had been stabilized with Kuntscher nails in radius and ulna 35 years ago.
      The loose ulna nail had been removed after ten weeks. Reosteosynthesis twelve
      months later with a Kuntscher nail and cerclages had led to osteomyelitis and
      persistent bone defect, possibly caused by galvanic reaction between the
      different alloyies. A lymphocyte transformation test with nickel sulphate
      confirmed an allergic reaction and supported the indication to late implant
      removal. After exposure of the nail's end by a short approach a sufficient take
      over of power to the implant was reached by a coupling pole. Extraction was
      stopped after two centimetres by a blockage of the nail. Widening the entry of
      nail and drilling its whole notch by means of a Kirschner wire using the
      radiolucent ruler and by the repeated extraction and reinsertion led finally to
      the complete removal of the nail. Whereas local pain is disappeared three month
      after removal presenting bland local findings the general condition is improved
      slowly. Already Kuntscher described the blockage of his nail after a short
      distance extraction. In addition to a number of not always successful means of
      extraction this method is described for the first time.

PMID- 11995227
TI  - [Linezolid--a new antibiotic for treatment of methicillin resistant
      Staphylococcus aureus infections in trauma surgery? Report of 2 cases].
AB  - PROBLEM: Infections with Methicillin-resistant Staphylococcus aureus are reported
      increasingly in intensive care unit and ward, that means not only a dangerous
      disease but also a considerable expenditure factor. METHODS: In trauma surgery we
      could observe the Linezolid treatment of 2 patients with a MRSA infection. After
      treatment with Vancomycin and further evidence of MRSA the application of
      Linezolid was continued during 3 weeks accompanied by further microbiologic
      investigations. RESULTS: In a 73 year old man with humerus shaft fracture the
      MRSA osteomyelitis was eradicated with Linezolid (600 mg/day per os over 3 weeks)
      after radical debridement and reosteosynthesis. The MRSA pneumonia in a 14 year
      old girl was treated successfully by Linezolid (600 mg/day i.v. over 3 weeks) and
      pneumotherapy. Follow up excluded further MRSA infection. CONCLUSIONS: Linezolid
      represents an efficient new reserve antibiotic. In case of pneumonia, severe skin
      and soft tissue infections good results can be expected. The treatment of
      osteomyelitis has been reported only in single cases.

PMID- 11995228
TI  - [Time optimized modern shock room management using digital techniques].
AB  - Emergency room management means time management. A time and four color based
      algorithm is described to improve workflow, follow up of diagnostic procedures
      and initial treatment. As a result introducing the time based interdisciplinary
      emergency algorithm within 60 minutes all necessary treatment and diagnostic
      procedures were completed. This algorithm is an effective tool to improve
      emergency room treatment.

PMID- 11995229
TI  - Finally, an APC code for observation: now find out the rules for getting paid.
AB  - A new ambulatory payment classification code was created for observation, with a
      payment rate of $351. Three diagnoses qualify for reimbursement: congestive heart
      failure, chest pain, and asthma. Active physician involvement in assessment and
      writing orders is required. Nurses should document the time when physician orders
      were started.

PMID- 11995230
TI  - Case study: ED acts quickly after anthrax.
AB  - After last year's anthrax attacks, EDs at Capital Health System in Trenton, NJ,
      had to address decontamination of large numbers of patients. Patients who didn't
      require decontamination were sent to the hospital's employee health facility so
      they could bypass the ED. Clinicians, nursing staff, educators, and paramedics
      were trained in the decontamination process. Direct communication with first
      responders was established with a portable scanner.

PMID- 11995231
TI  - Comply with regs for needlestick prevention.
AB  - A new compliance directive clarifies enforcement of regulations to prevent
      needlestick injuries. Involve staff in the selection of safer devices. Have
      nurses complete evaluation forms for new devices. Encourage nurses to ask
      questions about products even after the initial inservice.

PMID- 11995232
TI  - Report gives injury statistics from 9/11.

PMID- 11995235
TI  - Impacts of urban greenspace on offsetting carbon emissions for middle Korea.
AB  - Carbon dioxide is an important greenhouse gas and a major agent of climate
      change. This study quantified carbon (C) emissions from energy consumption and C
      storage and uptake by greenspace for three cities in middle Korea: Chuncheon,
      Kangleung, and Seoul. Carbon emissions were estimated using C emission
      coefficients for fossil fuels consumed. Carbon storage and uptake by woody plants
      were computed applying biomass equations and radial growth rates. The soils in
      Chuncheon were cored to analyze organic C storage. Annual C emissions were 37.0
      t/ha/yr in Kangleung, 47.2 t/ha/yr in Chuncheon, and 264.9 t/ha/yr in Seoul. Mean
      C storage by woody plants ranged from 26.0 to 60.1 t/ha for natural lands within
      the study cities, and from 4.7 to 7.2 t/ha for urban lands (all land use types
      except natural and agricultural lands). Mean annual C uptake by woody plants
      ranged from 1.60 to 3.91 t/ha/yr for natural lands within the cities, and from
      0.53 to 0.80 t/ha/yr for urban lands. There were no significant differences (95%
      confidence level) between the cities in C storage and uptake per ha for urban
      lands. Organic C storage in Chuncheon soils (to a depth of 60 cm) averaged 31.6
      t/ha for natural lands and 24.8 t/ha for urban lands. Woody plants stored an
      amount of C equivalent to 6.0-59.1% of total C emissions within the cities, and
      annually offset total C emissions by 0.5-2.2%. Carbon storage in soils was 1.2
      times greater than that by woody plants in Chuncheon. The C reduction benefits of
      woody plants were greater in Chuncheon and Kangleung, where areal distribution of
      natural lands was larger and the population density lower than in Seoul.
      Strategies to increase C storage and uptake by urban greenspace were explored.

PMID- 11995236
TI  - Applying voting theory in natural resource management: a case of multiple
      criteria group decision support.
AB  - Voting theory has a lot in common with utility theory, and especially with group
      decision-making. An expected-utility-maximising strategy exists in voting
      situations, as well as in decision-making situations. Therefore, it is natural to
      utilise the achievements of voting theory also in group decision-making. Most
      voting systems are based on a single criterion or holistic preference information
      on decision alternatives. However, a voting scheme called multicriteria approval
      is specially developed for decision-making situations with multiple criteria.
      This study considers the voting theory from the group decision support point of
      view and compares it with some other methods applied to similar purposes in
      natural resource management. A case study is presented, where the approval voting
      approach is introduced to natural resources planning and tested in a forestry
      group decision-making process. Applying multicriteria approval method was found
      to be a potential approach for handling some challenges typical for forestry
      group decision support. These challenges include (i) utilising ordinal
      information in the evaluation of decision alternatives, (ii) being readily
      understandable for and treating equally all the stakeholders in possession of
      different levels of knowledge on the subject considered, (iii) fast and cheap
      acquisition of preference information from several stakeholders, and (iv) dealing
      with multiple criteria.

PMID- 11995237
TI  - The health and visibility cost of air pollution: a comparison of estimation
      methods.
AB  - Air pollution from motor vehicles, electricity-generating plants, industry, and
      other sources can harm human health, injure crops and forests, damage building
      materials, and impair visibility. Economists sometimes analyze the social cost of
      these impacts, in order to illuminate tradeoffs, compare alternatives, and
      promote efficient use of scarce resource. In this paper, we compare estimates of
      the health and visibility costs of air pollution derived from a meta-hedonic
      price analysis, with an estimate of health costs derived from a damage-function
      analysis and an estimate of the visibility cost derived from contingent
      valuation. We find that the meta-hedonic price analysis produces an estimate of
      the health cost that lies at the low end of the range of damage-function
      estimates. This is consistent with hypotheses that on the one hand, hedonic price
      analysis does not capture all of the health costs of air pollution (because
      individuals may not be fully informed about all of the health effects), and that
      on the other hand, the value of mortality used in the high-end damage function
      estimates is too high. The analysis of the visibility cost of air pollution
      derived from a meta-hedonic price analysis produces an estimate that is
      essentially identical to an independent estimate based on contingent valuation.
      This close agreement lends some credence to the estimates. We then apply the meta
      hedonic-price model to estimate the visibility cost per kilogram of motor vehicle
      emissions.

PMID- 11995238
TI  - Evaluation of a forage allocation model for Theodore Roosevelt National Park.
AB  - We developed a forage allocation model using a deterministic, linear optimization
      module in a commercially available spreadsheet package to help resource managers
      in Theodore Roosevelt National Park (TRNP), North Dakota determine optimum
      numbers of four ungulate species, bison (Bison bison), elk (Cervus elaphus), mule
      deer (Odocoileus hemionus), and feral horses, in the Park. TRNP staff actively
      managed bison, elk, and feral horse numbers within bounds suggested by our model
      from 1983 to 1996. During this period, we measured vegetation at 8 grassland and
      12 wooded sites at 1-3 year intervals to determine if model solutions were
      appropriate for maintaining stable conditions in important plant communities in
      the Park. The data we recorded at these sites indicated minimal change in plant
      communities from 1983 to 1996. Changes in most vegetation categories that we
      expected when animal numbers exceeded model optimums for short periods (decreases
      in coverage/stem numbers of palatable plant species, increases in bare ground or
      unpalatable plant species) did not occur consistently under high or low
      precipitation conditions. The lack of sensitivity of our model to decreases in
      overall production of palatable plant species that occurred due to drought, fire,
      expansion of black-tailed prairie dog (Cynomys ludovicianus) colonies, and the
      spread of leafy spurge (Euphorbia esula) in areas of the Park where we did not
      have monitoring sites suggested that the model under-estimated the total number
      of ungulates that the Park could support. Management for population levels of
      ungulates defined by the model probably led to over protection of common plant
      communities and insufficient protection of rare plant communities. Detecting
      changes in rare plant communities could have been accomplished by re-designing
      our vegetation monitoring program, but changing emphasis to protection of rare
      plants would have likely promoted under use of grazing-tolerant habitat types,
      dissatisfaction in tourists visiting the Park to see large mammals, and large
      increases in cost and intrusiveness of management activities such as fencing and
      control of ungulate populations. The model was a flawed representation of grazing
      dynamics in TRNP, but we believe it succeeded in making management personnel
      aware of the biological constraints they face when making management decisions.

PMID- 11995239
TI  - Land application of phosphorus-laden sludge: a feasibility analysis.
AB  - An investigation was conducted to examine aerobic digestion of the phosphorus
      laden sludge produced at the Regina Wastewater Treatment Plant and feasibility of
      land use of this sludge combined with the dewatered anaerobically digested
      primary sludge from this plant. Experimental studies showed that aerobic
      digestion can be employed for the stabilization of the chemical sludge. Results
      of the feasibility analysis showed that mixing the two digested sludges met the
      heavy metal criteria set by various guidelines for agricultural use, presented
      the advantage of an increased concentration of nutrients and a decreased
      concentration of heavy metals, and a longer useful life of the agricultural site
      compared to using dewatered anaerobically digested primary sludge alone. Land
      application of the mixed digested sludges would be a more appropriate method of
      sludge disposal compared to the present practice of landfilling the dewatered
      sludge and lagooning the chemical sludge.

PMID- 11995240
TI  - Restoring grassland savannas from degraded pinyon-juniper woodlands: effects of
      mechanical overstory reduction and slash treatment alternatives.
AB  - Although the distribution and structure of pinyon-juiper woodlands in the
      southwestern United States are thought to be the result of historic fluctuations
      in regional climatic conditions, more recent increases in the areal extent, tree
      density, soil erosion rates and loss of understory plant diversity are attributed
      to heavy grazing by domestic livestock and interruption of the natural fire
      regime. Prior to 1850, many areas currently occupied by high-density pinyon
      juniper woodlands, with their degraded soils and depauperate understories, were
      very likely savannas dominated by native grasses and forbs and containing sparse
      tree cover scattered across the landscape. The purpose of this study was to
      evaluate the effectiveness of mechanical overstory reduction and three slash
      treatment alternatives (removal, clustering and scattering) followed by
      prescribed fire as techniques for restoring grassland savannas from degraded
      woodlands. Plant cover, diversity, biomass and nutrient status, litter cover and
      soil chemistry and erosion rates were measured prior to and for two years
      following experimental treatment in a degraded pinyon-juniper woodland in central
      New Mexico. Treatment resulted in a significant increase in the cover of native
      grasses and, to a lesser degree, forbs and shrubs. Plant species richness and
      diversity increased most on sites where slash was either completely removed or
      scattered to serve as a mulch. Although no changes in soil chemistry or plant
      nutrient status were observed, understory biomass increased over 200% for all
      harvest treatments and was significantly greater than controls. While treatment
      increased litter cover and decreased soil exposure, this improvement did not
      significantly affect soil loss rates. Even though all slash treatment
      alternatives increased the cover and biomass of native grasses, scattering slash
      across the site to serve as a mulch appears most beneficial to improving plant
      species diversity and conserving site resources.

PMID- 11995241
TI  - The trends of composite environmental indices in Korea.
AB  - In this paper we construct for the first time an annual Composite Environmental
      Index from 1986 to 1995 in Korea, which is useful for evaluating the efficiency
      of environmental policies. Nine types of environmental problems are examined. On
      average, the composite index has increased annually by 5.3% over the 1986-1995
      period, which implies that overall environmental quality has deteriorated
      gradually during this period. Problems such as the greenhouse effect, loss of
      biodiversity, natural resource depletion, and ecotoxication led to deterioration
      of environmental quality in the 1990s.

PMID- 11995242
TI  - The response of two arctic tundra plant communities to human trampling
      disturbance.
AB  - A 4-year study was conducted to evaluate the consequences of human trampling on
      dryas and tussock tundra plant communities. Treatments of 25, 75, 200 and 500
      trampling passes were applied in 0.75 m2 vegetation plots at a time of
      approximately peak seasonal biomass. Immediately after and 1 and 4 years after
      trampling, plots were evaluated on the basis of plant species cover, percent bare
      ground, vegetation height, and soil penetration resistance. One year after
      trampling, soils were collected for nitrogen analysis in highly disturbed and
      control plots. Immediately after trampling, 500 trampling passes resulted in
      approximately 50% cover loss in the dryas tundra and 70% cover loss in tussock
      tundra, but both communities showed a substantial capacity for regrowth. Plots
      where low and moderate levels of trampling were applied returned to pre
      disturbance conditions by 4 years after trampling, but impact was still evident
      in plots subjected to high levels of disturbance. These results suggest that
      these tundra communities can tolerate moderate levels of hiking and camping
      provided that use is maintained below disturbance thresholds and that visitors
      employ appropriate minimum-impact techniques. By utilizing this information in a
      visitor education program combined with impact monitoring and management, it is
      possible to allow dispersed camping and still maintain these vegetation
      communities with a minimum of observable impact.

PMID- 11995243
TI  - Geographic information system based manure application plan.
AB  - A geographic information system (GIS) based manure application plan has been
      developed for the site-specific application of animal waste to agricultural
      fields in the Westbrook sub-catchment of the Murray-Darling Basin, south-east
      Queensland, Australia. Sites suitable for animal waste application were
      identified using a GIS based weighted linear combination (WLC) model. The degree
      of land suitability for animal waste application was determined using a range of
      social, economic, environmental, and agricultural factors. As eutrophication and
      toxic blue-green algae blooms are a known problem in the catchment, the manure
      application rates were limited to the rate of crop phosphorus removal. Maximum
      manure application rate was calculated spatially by taking the crop nutrient
      (P2O5) requirement and the manure nutrient (P2O5) content into account. The
      environmental suitability of the fields receiving animal waste was considered in
      prescribing the final application rate of solid and liquid manures generated by
      local animal production facilities. The degree of site suitability of the
      agricultural fields was also used to suggest manure management practices to
      minimise the socio-environmental risks and increase the nutrient use efficiency
      of the applied manure. The amount of ammonium nitrogen (NH4-N) that would be
      added to the soil by satisfying the P2O5 requirement using manure sources was
      also calculated and an applied NH4-N map was created. This map could be used to
      assist farmers identify additional nitrogen requirements after manure
      application.

PMID- 11995244
TI  - [Appearance of Helicobacter pylori antigen in stool specimens of children with
      chronic gastritis].
AB  - Various examinations are successfully applied for the diagnosis of Helicobacter
      pylori infection, but non-invasive techniques are still required for the
      therapeutic monitoring after eradication therapy, especially in children. In the
      search for new non-invasive techniques to diagnose H. pylori infection, we
      evaluated an EIA for H. pylori antigen in stool (HpSA). Our study included 62 H.
      pylori-positive children with chronic gastritis. H. pylori infection was
      diagnosed by using the culture of gastric mucosa before treatment
      (clarithromycin, amoxicillin, omeprazole for 7 days) and after 3 months following
      treatment. Before therapy, stool antigen was detected in 55 out of 62 H. pylori
      positive patients, which indicates that the sensitivity of the test was 88.7%.
      After therapy, eradication was obtained (and confirmed by culture) in 53 out of
      62 subjects. When the HpSA test was used, the ratio was 52 out of 62. The
      sensitivity, specificity of HpSA was 88.9% and 96.2, respectively. The accuracy
      of the HpSA test for the detection of H. pylori in human stool 3 months after
      treatment is comparable with the accuracy of the culture results.

PMID- 11995245
TI  - [Correlation between body mass index, lipoprotein (a) level and positive family
      history of cardiovascular diseases in children and adolescents with obesity,
      hypertension and diabetes].
AB  - The study was carried out in a group of 285 children and adolescents aged 4-20
      yrs. Children were divided according to their main disease: group with obesity,
      obesity and coexisting hypertension, hypertension and diabetes. Each group was
      divided into children with positive or negative family history of cardiovascular
      diseases. We assessed routine lipid parameters, body mass index and new
      atherosclerosis risk factors: lipoprotein (a), apolipoproteins A-I and B,
      homocysteine, fibrinogen, t-PA and PAI-1. Positive family history of
      cardiovascular diseases was found in 28% families, and in 8% families it was
      premature cardiovascular disease. In 48% children we found hypertension in
      family. Children with positive family history had significantly higher body mass
      index (25.4 vs 23.8 kg/m2). In the group with obesity and hypertension we found
      significantly higher cholesterol (182 vs 160 mg/dl) and LDL-cholesterol level
      (114 vs 93 mg/dl). Lipoprotein(a) level was significantly higher in children with
      positive family history (38 vs 28 mg/dl). Significant differencies were also
      found in apolipoprotein B level (90 vs 84 mg/dl). In logistic regression analysis
      only BMI and lipoprotein(a) were significant in predicting future cardiovascular
      events in children. Obese, hypertensive and diabetic children often come from
      families with cardiovascular diseases. Hypertension is the most often prevalent
      atherosclerosis risk factor in families. Children with positive family history of
      cardiovascular diseases have significantly higher body mass index. Out of new
      atherosclerosis risk factors lipoprotein(a) and apolipoprotein B may have real
      value in predicting future cardiovascular disease in the child. The aim of the
      study was to compare obese, hypertensive and diabetic children with positive and
      negative family history of cardiovascular diseases. In the work we have tried to
      find which of the new atherosclerosis risk factors may have the real value in
      predicting future cardiovascular events in children already predisposed to
      atherosclerosis.

PMID- 11995246
TI  - [Birth weight, health status and physical development of young men after 20
      years].
AB  - The aim of the study was to assess the health status and physical development of
      young men with low birth weight (LBW) compared to normal birth weight (NBW). The
      study was based on the birth cohort of children born in Warsaw at six obstetric
      wards in 1970-74. The data from the medical records of military conscription
      units, concerning 682 persons with LBW and 408 persons with NBW, were taken for
      comparison. Mean height and weight of LBW persons were lower then for those with
      NBW, with similar weight-for-height proportions. The prevalence of hearing loss
      was higher among LBW then NBW individuals despite similar rates of ear disorders
      assessed at the mid-point of the follow-up. Also, neurological disorders were
      more prevalent among LBW then NBW individuals at the time of conscription, which
      could not be fully ascribed to the possible birth injuries.

PMID- 11995247
TI  - [Rheumatic syndromes during the course of HCV infection].
AB  - The aim of the study was to evaluate clinical features and serological
      abnormalities in patients(pts) with rheumatological symptoms in the course of HCV
      infection (5 pts) and interferon-alpha treatment (2 pts). The diagnosis of
      hepatitis C was based on positive history on jaundice and risk factors of HCV
      infection, abnormal liver laboratory tests, the presence of anti-HCV and HCV-RNA
      and on results of liver biopsy. Among the patients with rheumatological features
      in the course of HCV infection seropositive arthritis in 4 pts, leucocytoclastic
      vasculitis, clinical and serological manifestations of mixed cryoglobulinemia-in
      3 pts were observed. Glomerulonephritis, Raynaud's phenomenon and antinuclear
      antibodies were found in 2 pts. Sjogren's syndrome with anti-Ro/La antibodies,
      polyneuropathy and myalgia were observed in single cases. The most frequent
      therapy were corticosteroids alone or in combination with chlorochine or
      azathioprine. Arthritis, leucocytoclastic vasculitis and serological
      abnormalities: antinuclear antibodies, rheumatoid factor and low complement were
      seen in 2 pts with rheumatological features after the IFN-alpha treatment of HCV
      infection. Myalgia and xerostomia with anti-Ro antibody were found in one
      patient; lupus-like disease with anti-dsDNA antibody and autoimmune thyroiditis
      in one patient. The therapy of these two cases was to withdraw interferon-alpha.

PMID- 11995248
TI  - [The effect of low dose methotrexate treatment on bone mineral density in
      patients with rheumatoid arthritis].
AB  - OBJECTIVE: To evaluate the bone mineral density (BMD) in patients with rheumatoid
      arthritis (RA) treated with MTX or SF. The study consisted of 56 premenopausal
      women diagnosed with rheumatoid arthritis (RA). Bone mineral density (BMD) of the
      lower lumbar spine was assessed before starting treatment, and again after 12
      months of treatment. DEXA scanning was used to evaluate BMD. Corticosteroids or
      other substances known to affect bone metabolism were not administered. 45 women
      completed the study, of whom 23 were treated using SF and 22 MTX. The average
      dosage of MTX used was calculated to be 590 mg. A significant difference in the
      BMD of SF and MTX patients was not observed in the pretreatment phase, nor after
      12 months of treatment. However, in all patients a significant reduction of BMD
      was observed, irrelevant of the choice of drug. The average loss of bone mass was
      1.7% and 1.4% in the MTX and SF groups, respectively. MTX therapy administered in
      low doses as assessed after 12 months did not cause a rapid decrease of bone
      density in patients with RA.

PMID- 11995249
TI  - [Skin changes during the course of selected endocrinologic diseases in children
      and adolescents].
AB  - The authors presented skin lesions which may be observed in selected
      endocrinopathies in children and adolescents. Functional disturbances of
      endocrine glands in which skin lesions may develop are dysfunction of the
      adrenals, gonads in case of children, thyroid diseases and diabetes type 1. The
      authors presented also a detailed description of skin symptoms observed in
      hyperthyrosis and hypothyrosis. They emphasised that the most common form of
      hyperthyrosis in children and adolescents is Graves disease. Also broadly
      dermatological lesions which may develop in diabetes type 1 they described.

PMID- 11995250
TI  - [Modern aspects of bioterrorism].
AB  - The study includes a survey of issues connected with the possibility of micro
      organisms use in bioterrorist attack. The attention was drawn to the need of
      society co-operation in nuclear, chemical and biological weapons use prevention.
      The fundamental importance is a quick diagnosis, skills of undertaking preventive
      activities, treatment intending to save a great number of human beings.

PMID- 11995251
TI  - [Asthma with aspirin intolerance].
AB  - We described asthma with sensitivity to aspirin and other nonsteroidal anti
      inflammatory drugs (NSAID). It was presented clinical picture, diagnosis and
      pathomechanism of this syndrome. Specially was described the cyclooxygenase
      theory and genetic risk of aspirin induced asthma as well as tolerability of the
      new COX-2 inhibitors.

PMID- 11995252
TI  - [Significance of immunotherapy in treatment of bronchial asthma].
AB  - When first used, immunotherapy was applied to treatment of infectious diseases.
      Its high effectiveness gave an impulse to introduce this method in the treatment
      of allergic diseases, including bronchial asthma. In contrast to pharmacological
      treatment which treats only the symptoms in allergies, immunotherapy is presently
      considered to be the only causative treatment. Several conditions have to be
      fulfilled to obtain the effect of such treatment. Appropriate patients selection,
      use of the etiologically correct vaccine and continuing the treatment throughout
      several seasons are the conditions for the therapeutic success. In nonatopic
      intrinsic asthma or in atopic asthma complicated by bacterial infections the use
      of autologic or polyvalent (standard) bacterial vaccine should be considered.
      Because immunotherapy brings a risk of serious side effects such as anaphylactic
      reaction, only allergy specialist should be entitled to decide of the
      introduction of such treatment and to supervise its course.

PMID- 11995253
TI  - [Health threats for children in the modern building trade].
AB  - Changes in building industry during last 30 years in search of economic
      technologies and building materials ended in creating airtight and energy-saving
      constructions with reduced ventilation. As a result, diminish exchange between
      internal and external air, leads to cumulation of various chemicals and organic
      substances in our houses. Concentrated oxidation products (CO2, CO, NO2, nicotine
      smoke), vaporizing substances (formaldehyde, NH3, aromatic hydrocarbons) might
      irritate mucouses, promote or intense respiratory tract infections, allergic
      diseases or bronchial asthma. Higher risk of atopic diseases and bronchial asthma
      also arises from proliferation of fungus, bacteria and mites in modern interiors,
      which are quite convenient for it. Buildings with microclimate, which is
      dangerous for human health, are termed "sick buildings". Diseases that develop
      under their influence are called BRI (building related illnesses). Children are
      most exposed on them, especially under municipal conditions, because they spend
      majority of their time at home.

PMID- 11995254
TI  - [Ototoxic complications of chemotherapy].
AB  - Ototoxicity of drugs is still an important problem in the management of many
      disorders. Some issues of inner ear impairment following administration of
      antibiotics, cytostatics, salicylates and nonsteroidal antiinflammatory drugs are
      presented in the article. Some of the clinical symptoms indicative to the
      possibility of complications in the inner ear: tinnitus, hearing loss, giddiness
      and vertigo. Negative side effects of drugs might occur after general as well as
      in local treatment, e.g. ear drops. Antibiotics from the aminoglycoside group
      reveal a particularly high ototoxicity. The risk of the occurrence of ototoxicity
      increases in patients with kidney and inner ear disorders, treated with more than
      one ototoxic drug and in patients over 65 years and under 3 years of age.
      Prophylactics against complications consists of analysis of indications of
      treatment with the above mentioned drugs, its proper dosage, knowledge of the
      risk groups, daily observation on the patient and monitoring of the hearing and
      balance organs. Treatment of complications usually does not result in positive
      effects.

PMID- 11995255
TI  - [Diagnostic and therapeutic standards for rheumatic diseases in children].
AB  - The rheumatic diseases constitute a significant group of chronic illnesses
      affecting children of all ages, including adolescence. This chapter provides an
      overview of rheumatic diseases and medical treatment options. The author
      describes in detail diagnostic and therapeutic standards proceedings in rheumatic
      fever, juvenile chronic arthritis, systemic lupus erythematosus and Kawasaki
      disease. The article contains the newest data from literature about new therapy
      trials in above mentioned diseases.

PMID- 11995256
TI  - [Classification criteria and clinical picture of juvenile idiopathic arthritis].
AB  - In recent years a new nomenclature and classification childhood chronic arthritis
      has been introduced. The terms juvenile chronic arthritis and juvenile rheumatoid
      arthritis--have been replaced by juvenile idiopathic arthritis (JIA). The term
      JIA was adapted to indicate a childhood onset (before the 16th. birthday)
      characterized primarily by arthritis lasting for at least 6 weeks, and the cause
      haven't been found so far. In this paper the diagnosis and clinical course
      systemic arthritis, polyarthritis and oligoarthritis were characterized. The
      current therapeutic approach to JIA consists a complex management as the
      administration of antiinflammatory, immunosuppressive and immunomodulatory drugs-
      as well as rehabilitation.

PMID- 11995257
TI  - [The role of pathomorphologic diagnosis in differentiating intestinal
      inflammatory diseases].
AB  - The principles of collaboration between a gastrologist and a pathomorphologist in
      diagnosis of the intestinal diseases were presented. The optimal criteria of
      drawing and fixing cytological and tissue samples were presented. The importance
      of extensive clinical information for pathomorphological diagnosis was proved. It
      was indicated that an early collaboration between a gastrologist and a
      pathomorphologist in the process of clinical diagnostic planning is necessary.

PMID- 11995258
TI  - [Liposomes--therapeutic progress and technological problems].
AB  - Liposomes represent globular vesicles composed of an aqueous core and one or
      several phospholipid bilayers. They can encapsulate hydrophilic or lipophilic
      drugs used in therapy and diagnostic imaging. Liposomes provide protection of the
      active substances, sustained or controlled release and also targeted delivery of
      drugs to specific cells, tissues, organs. Easy oxydation of phosphatidylcholin
      (lecithin)--the main membrane component--is the limitation of the introduction of
      liposomes to the medicinal practice in a broader scale. Unsatisfying chemical
      stability of lecithin has an unfavourable influence on drug and liposome
      stability. Liposomes decompose during storage and leakage of the encapsulated
      drug occurs. A review of advantages of application of liposomes in medicine and
      methods of increasing their stability was presented.

PMID- 11995259
TI  - [Immunologic conditions for efficient vaccination].
AB  - The quality of the vaccine and the way of immune response determine the result of
      vaccination, its safety and efficiency. The border between expected benefits and
      unexpected adverse side effects is determined by the degree of immunoregulatory
      competence of immune system. On the grounds of current views on the role of
      immunoregulatory disorders in development of allergic and auto aggressive
      diseases, the authors consider the conditions in which the vaccinations may
      contribute for appearance of erroneous immune responses.

PMID- 11995260
TI  - [Spirometry evaluation of montelukast treatment in children with bronchial
      asthma].
AB  - Difficulties associated with the management of asthma were the cause of using the
      leukotriene antagonists. There was performed a randomised group of 31 children
      aged 6-18 y (mean 12 yrs., 10 girls and 21 boys) with persistent asthma and poor
      asthma control. Montelukast was administered once daily, 5-10 mg depended of the
      age of the patients. This treatment was conducted for three months. Montelukast
      significantly improved pulmonary lung function (as measured by spirometry).
      Another effect of montelukast treatment was possibility the reduction beta 2
      agonist use and the required dose of inhaled corticosteroids.

PMID- 11995261
TI  - [The effect of inhaled heparin on post-leukotriene bronchoconstriction in
      children with bronchial asthma].
AB  - Heparin besides its anticoagulant properties, possesses anti-inflammatory
      actions. Inhaled heparin has been shown to reduce early and late phase of
      asthmatic reaction and suppresses allergen induced rise in bronchial
      hyperreactivity. The exact mechanism of heparin action in bronchial asthma
      remains obscure. The mechanism involved in the control of bronchial
      hyperreactivity by heparin has been studied little and is yet poorly understood.
      The purpose of the present study was to investigate the effect of inhaled heparin
      on the airway response to leukotriene D4 Fourteen children with typical history
      of mild atopic asthma participated in this randomized, double-blind, placebo
      controlled and cross-over study. At the first visit subjects underwent
      provocation challenge test with leukotriene D4. Patients came back 14 days later
      to inhale heparin or placebo followed by provocation test with leukotriene. The
      third study day was 14 days after the second day and provocation test was
      performed in the same manner except for that patients who inhaled heparin at the
      second visit, now were administered placebo and opposite. Ten patients completed
      the study. One patient was withdrawn from the study because of consent withdrawal
      and three patients were unable to complete the provocation test because of asthma
      exacerbation. Single dose of inhaled heparin significantly decreased bronchial
      hyperreactivity to leukotriene in children with mild asthma (p = 0.005). PC20L
      after heparin inhalation increased in eight patient and decreased in two. It has
      been shown that histamine, metacholine, and leukotriene play a role in eosinophil
      recruitment to the airway. Since histamine, metacholine and leukotriene act
      through receptor binding to protein G, it is possible that heparin (by displacing
      eosinophil proteins from receptor-protein G binding) restore binding between
      receptor and G protein and in such mechanism, decrease bronchial hyperreactivity
      to leukotriene. In our study heparin was inhaled just before leukotriene
      provocation test and thus the effect of heparin on eosinophil proteins is less
      likely possible.

PMID- 11995262
TI  - [The effect of triamcinolone acetonide, montelukast, nedocromil sodium,
      formoterol on levels levels of sICAM-1, sIL-2R in serum and clinical course of
      asthma in children].
AB  - One of the characteristics of asthma is the variability of inflammation. Thus, it
      is important to monitor inflammation serially in asthma, e.g. by the use of
      peripheral blood markers. To evaluate the effect of treatment on allergic
      inflammation, we measured serum levels of sIL-2R, sICAM-1 and clinical parameters
      before and after 4 weeks treatment with triamcinolon, montelukast, nedocromil and
      formoterol. It was 8 week, placebo-controlled and randomized, double blind trial
      of 158 children with moderate atopic asthma. Patients were randomly allocated to
      received 400 micrograms triamcinolon (n = 28), 5 or 10 mg (according to age)
      montelukast (n = 27), 16 mg nedocromil (n = 30), 24 micrograms formoterol (n =
      29) or placebo (n = 44). 140 children completed the study. After treatment with
      triamcinolon, montelukast and nedocromil sIL-2R and sICAM-1 serum level
      significantly decreased, and all clinical parameters improved; treatment with
      triamcinolon had the strongest effect on most parameters (except of FEV1). Mean
      sIL-2R before and after treatment with triamcinolon were 724.1 pg/ml and 486.1
      pg/ml respectively (p < 0.001); with nedocromil were 760.2 pg/ml and 596.7 pg/ml
      respectively (p < 0.001); with montelukast were 617.9 pg/ml and 491.2 pg/ml
      respectively (p < 0.001); with formoterol were 705.4 pg/ml and 698.9 pg/ml
      respectively (p = 0.8). Mean sICAM-1 serum levels before and after treatment with
      triamcinolon were 262.4 ng/ml and 210.4 ng/ml respectively (p < 0.001); with
      nedocromil were 292.9 ng/ml and 258.4 ng/ml respectively (p < 0.001); with
      montelukast were 277.7 ng/ml and 242.9 ng/ml respectively (p < 0.001); with
      formoterol were 262.6 ng/ml and 260.0 ng/ml (p = 0.6). We found significant
      correlation between: sIL-2R and hyperresponsiveness, sICAM-1 and hyper
      responsiveness, FEV1 and sICAM-1, FEV1 and sIL-2R, sIL-2R and sICAM-1 after
      treatment. This study shows that triamcinolon, montelukast and nedocromil
      contribute to inhibition of allergic inflammation by decreasing sIL-2R and sICAM
      1 serum levels. The serum level of sIL-2R and sICAM-1 seem to be a good clinical
      marker of monitoring the disease; their levels decrease after treatment together
      with improvement in hyperresponsiveness and clinical parameters.

PMID- 11995263
TI  - Drug and Therapeutics Bulletin at 40.
AB  - In April 1962, Consumers' Association published the first issue of a British
      edition of the American Medical Letter on Drugs and Therapeutics. A year later,
      formal ties with the parent journal were severed, the title was changed, and Drug
      and Therapeutics Bulletin (DTB) was launched. Initially, articles in DTB were
      brief (each around 500 words), references few (rarely more than five) and the
      circulation around 5,000. Gradually, articles and reference lists have
      lengthened, and our circulation has grown to 130,000 (a figure bolstered by bulk
      purchasing agreements with Departments of Health, or their equivalents, in the UK
      and Eire).

PMID- 11995264
TI  - Management of infective endocarditis.
AB  - Infective endocarditis, in which infection or infective vegetations develop on
      heart valves or other endocardial surfaces, causes considerable morbidity and
      mortality. Prompt diagnosis and treatment can improve outcome and are therefore
      essential. Here, we discuss the management of infective endocarditis,
      concentrating on adult patients.

PMID- 11995265
TI  - Levetiracetam--a new drug for epilepsy.
AB  - Levetiracetam (Keppra--UCB Pharma) is a new anti-epileptic drug, marketed in the
      UK since 2000. It is licensed for use as adjunctive treatment for partial
      seizures, with or without secondary generalisation, in people aged over 16 years.
      The company claims that levetiracetam is "highly effective", with a "therapeutic
      starting dose", "excellent tolerability", and "no known drug/drug interactions".
      Here, we discuss the place of levetiracetam in the treatment of patienTs with
      epilepsy.

PMID- 11995266
TI  - Patients' right to refuse treatment.

PMID- 11995267
TI  - Gamma camera positron emission tomography: implications for clinical and research
      studies.

PMID- 11995268
TI  - Update on pancreatic cancer.
AB  - Pancreatic cancer is one of the commonest causes of cancer death worldwide.
      Patients with pancreatic cancer benefit from resectional surgery (improved
      quality of life) and adjuvant treatment (enhanced survival). This review covers
      advances in the understanding of the development of pancreatic cancer, state-of
      the-art clinical management and, finally, novel treatment and screening
      techniques.

PMID- 11995269
TI  - Management of osteoid osteoma.
AB  - An osteoid osteoma is a benign bone tumour which can cause severe pain. Diagnosis
      is often delayed, as it may mimic other musculoskeletal conditions. The most
      pertinent investigations for diagnosis are a bone scan and computed tomography of
      the area of increased uptake. Treatment with minimally invasive techniques allows
      early return to full function.

PMID- 11995270
TI  - Ovarian cancer screening.
AB  - Ovarian cancer is the fourth commonest cause of cancer deaths in women.
      Multimodal screening with serum CA125 and transvaginal ultrasonography have been
      shown to improve survival. However, the results so far do not justify routine
      screening until the impact of screening on mortality has been assessed in larger
      randomized trials.

PMID- 11995271
TI  - Kidney cancer: current management guidelines.
AB  - Renal cell carcinoma accounts for 2% of all cancers. Medical progress has
      improved the outcome of early but not advanced disease. This article highlights
      the current practice for the management of renal cell carcinoma.

PMID- 11995272
TI  - Effect of nurse colposcopists on a hospital-based service.
AB  - The number of colposcopies performed annually in the UK is increasing. Nurse
      colposcopists have been introduced by many units to cope with this workload. The
      small amount of evidence to support the introduction of nurse colposcopists
      suggests that nurses are viable alternative providers of colposcopy. This study
      compares the performance of nurse colposcopists with that of doctors.

PMID- 11995273
TI  - Priapism: a medical emergency.
AB  - Priapism is defined as a prolonged penile erection that fails to subside despite
      orgasm. It is a medical emergency which should be diagnosed and treated early to
      preserve erectile function and avoid corporal fibrosis resulting from anoxia of
      the corporal tissue. Decompression is usually successful with no permanent damage
      if treatment is provided within 12 hours of onset.

PMID- 11995274
TI  - Biliary tract emergencies.
AB  - Gallstones are responsible for the majority of biliary tract emergencies and will
      be the main focus of this article. Gallstones present with features related to
      the site of the calculi and are therefore considered separately.
      Cholecystolithiasis refers to gallstones confined to the gallbladder, whereas
      choledocholithiasis refers to gallstones within the common bile duct.

PMID- 11995275
TI  - Once-weekly treatment for osteoporosis.
AB  - Daily oral bisphosphonates are a well-established treatment option for
      osteoporosis. However, many patients find the daily dosing regimen inconvenient.
      Once-weekly alendronate offers greater convenience to patients while providing
      equal efficacy.

PMID- 11995276
TI  - Distance learning to support postgraduate training in obstetrics and gynaecology.
AB  - A number of major distance learning programmes have been launched by the medical
      Royal Colleges for the purposes of training and/or continuing medical education.
      The most recent is 'StratOG', a modular programme published by the Royal College
      of Obstetricians and Gynaecologists (RCOG) and aimed primarily at candidates for
      the part 2 RCOG Membership examination.

PMID- 11995277
TI  - Diagnosis and immediate care of fractures of the knee.

PMID- 11995278
TI  - Unusual causes of severe orthostatic hypotension.

PMID- 11995279
TI  - An ex-intravenous drug addict with confusion and apathy.

PMID- 11995280
TI  - Elevated alpha-fetoprotein levels in a woman with ovarian teratoma.

PMID- 11995281
TI  - Safety of diagnostic ultrasound.

PMID- 11995282
TI  - Is surgery delayed by HMO surgery denied?

PMID- 11995283
TI  - Can nurses testify as to 'dying declarations?'. Case of point: State v. McHoney,
      2001 WL 283241 SE.2d - SC.

PMID- 11995284
TI  - NY: public health nurse's bizarre behavior: RN fails competency exam--appeals
      termination.

PMID- 11995285
TI  - TX: LVNs injured transferring Parkinson's patient: LVNs negligence suit against
      patient dismissed.

PMID- 11995286
TI  - Nurse 'forgot' & gave blood to Jehovah's Witness. Case on point: Tatman v. Fort
      Sanders Regional Medical Center, 2001 WL 378688 SO.2d - TN.

PMID- 11995287
TI  - [It is not always possible to fulfill the dream of independence. It is necessary
      to overcome professional and bureaucratic hurdles, if one chooses autonomous
      nursing].

PMID- 11995288
TI  - [Consultant nursing--a change in the nursing system].

PMID- 11995289
TI  - [Health 21--Goal 17: Financing of public health and resource allocation].

PMID- 11995290
TI  - [Trends in extramural nursing care].

PMID- 11995291
TI  - Role of stored iron in atherosclerosis.
AB  - Myocardial infarction remains the No. 1 killer of American men and women, with a
      death rate of 225,000 per year, and stroke, the third leading cause of death in
      the United States, afflicts about 600,000 per year. The combined financial burden
      of these diseases is approximately $134 billion per year. Therefore,
      interventions that reduce mortality and suffering will have a significant impact
      on the health care system. This article summarizes research conducted during the
      last 2 decades that addresses the idea that stored iron plays a role in the
      pathogenesis of atherosclerosis and that iron reduction through phlebotomy may
      play a role in the treatment or prevention of atherosclerosis. Body iron stores
      rise after adolescence in men and menopause in women. This rise has been linked
      to the pathogenesis of atherosclerosis through iron-induced oxidation of low
      density lipids and foam cell formation. However, the available evidence on the
      iron hypothesis remains circumstantial. Reduction of body iron stores in the
      setting of a controlled, prospective intervention trial is necessary to determine
      whether the amount of stored iron is related to clinically meaningful vascular
      disease. Such a study is feasible because reduction in iron stores can be
      achieved safely and predictably without induction of iron deficiency by graded
      phlebotomy. The Iron and Atherosclerosis Study (FeAST), a Veteran's
      Administration Cooperative Study, is under way to test this concept.

PMID- 11995292
TI  - Patient psychologic preparation for invasive procedures: an integrative review.
AB  - If the physiologic symptoms of anxiety occur during a critical procedure, the
      length and difficulty of the procedure may be increased, inaccurate data may be
      obtained from the procedure, and physical harm may occur as a result. To avoid
      these negative outcomes, it would be beneficial to reduce the amount of anxiety
      felt by patients undergoing invasive procedures by psychologically preparing them
      for the procedure. Fourteen studies were found that examined the effects of
      different types of preparational treatment on the anxiety levels of patients
      undergoing procedures in the hospital. Overall, the research studied strongly
      supports the notion that preprocedural intervention reduces the amount of anxiety
      felt by the patients. The question remains as to what type of preprocedural
      preparation works best to reduce anxiety. Because this research applies to any
      procedure performed in a hospital, it is appropriate to extend the implications
      to include peripheral angiography. It is essential for vascular nurses to
      implement some type of psychologic preparation for their patients undergoing
      vascular procedures to improve their outcome and quality of life after the
      procedure.

PMID- 11995293
TI  - Prevention of venous ulceration by use of compression after deep vein thrombosis.
AB  - Venous ulcers may result from damage to the lining of the veins after an
      occurrence of deep vein thrombosis (DVT). As the pressure in the damaged venous
      system remains pathologically high, a result of DVT, swelling develops,
      hemosiderin staining develops around the ankle area, and varicosities often
      develop. These symptoms are part of the postphlebitic syndrome and are a
      precursor to formation of the chronic venous ulcer. The mainstay of treatment or
      prevention for venous ulcers remains compression therapy. In spite of the
      evidence that compression is necessary to reduce edema and allow the ulcer to
      heal, many patients still are not using compression after DVT to prevent ulcer
      formation. This article describes the prevalence, cost, etiology, and
      pathophysiology of postphlebitic syndrome and presents the nursing intervention
      of compression therapy as an ulcer prevention strategy for the patient with DVT.
      A variety of compression strategies are discussed. A case study of a patient in
      need of compression therapy is presented.

PMID- 11995294
TI  - Buerger's disease.
AB  - Buerger's disease (thromboangiitis obliterans) is rarely seen in most clinical
      practices. Many advanced practice nurses may only see one or two cases in their
      lifetime, and some hospital-based nurses may never see the disease. Information
      about this occlusive peripheral arterial disease must be obtained for the
      vascular nurse to care for patients with the disease. The subject of Buerger's
      disease is not common in the literature, and little is found in nursing texts or
      journals. The care of the disease involves nursing emphasis on lifestyle changes.
      This article will address definition, history, review of literature, and
      pathophysiology. The recommendations for diagnosis, treatment, and nursing care
      interventions also will be reviewed.

PMID- 11995295
TI  - Acute versus chronic aortic occlusion .

PMID- 11995296
TI  - There are exceptions to the 'going & coming' rule.

PMID- 11995297
TI  - Failure to keep physicians informed--death results. Case on point: Winstead v.
      Claiborne County Hospital, 2001 WL 293005 So.2d- TN.

PMID- 11995298
TI  - TX: nurse supervisor blocks exit with chair: terminated nurse sues for false
      imprisonment.

PMID- 11995299
TI  - TX: did nurses fail to timely call doctor?: Sufficient evidence for verdict for
      hospital found.

PMID- 11995300
TI  - Were nurses overzealous in obtaining consent for organ donation? Case on point:
      Lanier Memorial Hospital v. Andrews, 2001 WL 367596 So.2d- AL.

PMID- 11995301
TI  - UN Special Session: global communications, international politics and the stigma
      & silence of AIDS.

PMID- 11995302
TI  - The requirement to disclose unanticipated outcomes.

PMID- 11995303
TI  - Adolescents and healthy heart living.

PMID- 11995304
TI  - Navy nursing aboard a US Navy carrier.

PMID- 11995305
TI  - Laser hair removal, sclerotherapy, injection of collagen and botox.

PMID- 11995306
TI  - Professional practice advocacy.

PMID- 11995307
TI  - Model for safe medication dispensing practices for hospitals.

PMID- 11995308
TI  - Model for safe medication administration practices for hospitals.

PMID- 11995309
TI  - Clinical excellence exemplar.

PMID- 11995310
TI  - Do union contracts preempt emotional distress claims?

PMID- 11995311
TI  - Did nurses pressure pt. to sign blank consent form? Case on point: Christie v.
      Gilmore, 2001 WL 789613 S.W.3d-TX.

PMID- 11995312
TI  - TX: patient sitting on bed falls--aide nearby: bed is not "equipment" so as to
      waive immunity.

PMID- 11995313
TI  - OH: did fracture cause fall or vice versa?: Lack of expert testimony as to
      proximate cause.

PMID- 11995314
TI  - Terminated nurse alleges hospital violated ADA. Case on point: Phelps v. Optima
      Health Inc., 2001 WL 563921 N.E.2d-NH.

PMID- 11995315
TI  - [Blood conservation in thoracic aortic surgery with total cardiopulmonary
      bypass].
AB  - BACKGROUND: In thoracic aortic surgery, a large number of homologous transfusions
      sometimes cause systemic inflammatory response, which may lead to pulmonary
      dysfunction, renal dysfunction and brain edema. To predict the need for
      homologous blood transfusion in aortic surgery, we use blood transfusion index
      (preoperative Ht x body weight) to predict the magnitude of homologous
      transfusion. PATIENTS AND METHODS: From Dec 1997 to May 2000, 59 consecutive
      patients were underwent thoracic aortic graft replacement with total
      cardiopulmonary bypass. These patients were divided in 2 groups, who were
      underwent graft replacement without blood transfusions, and who needed blood
      transfusions. Each group was compared in age, sex, emergency, Ht, CPB time, blood
      transfusion index and operative mortality. RESULTS: Forty patients (67.7%) did
      not required blood transfusion. In elective cases (32 cases), 84.3% were
      underwent operation without blood transfusion. There was no significant
      difference between 2 groups in terms of age and mean bypass duration. Blood
      transfusion index was significantly higher in transfusion group (2,320 +/- 784)
      compared with that in not transfusion group (1,445 +/- 706). CONCLUSION: Blood
      transfusion index was useful preoperative parameter to predict the need for
      homologous transfusion.

PMID- 11995316
TI  - [Successful lingular segmentectomy using bronchoplasty in a patient with early
      hilar second primary lung carcinoma].
AB  - A 71-year-old man was admitted to our hospital with a small protrusive lesion at
      the lingular orifice of the left upper bronchus. He had undergone a right lower
      lobectomy and mediastinal dissection for lung carcinoma (large cell carcinoma,
      pT1N0M0) 14 months earlier. Early hilar squamous cell carcinoma was diagnosed by
      chest radiograph, CT and transbronchial biopsy. We performed a lingular
      segmentectomy with wedge resection of the left upper bronchus and N 1 lymph node
      dissection. The tumor was histopathologically diagnosed as early hilar second
      primary lung carcinoma. The patient's postoperative course was uncomplicated. At
      present, he is alive with good respiratory condition and without any evidence of
      recurrence. Segmentectomy is appropriate for a patient with contralateral second
      primary lung carcinoma as well as a patient with early hilar lung carcinoma.
      Bronchoplasty seems to increase the likelihood that such a patient will be a
      candidate for segmentectomy.

PMID- 11995317
TI  - [First successful clinical application of tissue engineered blood vessel].
AB  - With this tissue engineering (TE) technique, the peripheral pulmonary artery was
      successfully reconstructed, using the patient's own venous cells in a 4-year-old
      girl, 2 years after Fontan procedure. A 4-year-old girl was given a diagnosis of
      single right ventricle, double-outlet right ventricle and pulmonary atresia. She
      underwent left modified Blalock-Taussig shunt at a month old, pulmonary artery
      angioplasty at a year and 3 months old, and bidirectional cavopulmonary shunt at
      2 years and a month old. She underwent again pulmonary artery angioplasty and
      Fontan operation at 3 years and 3 months. An angiographical examination 7 months
      after the operation revealed total occlusion of the right intermediate pulmonary
      artery. TE technique using autologous cells was indicated. The application of
      this procedure was approved by the ethical committee in Tokyo Women's Medical
      University. The patient's parents were thoroughly informed and signed a consent
      form. Approximately 2 cm of the peripheral vein was explanted under sterile
      conditions. The tissue was minced, placed in tissue culture dishes and cultured
      at 37 degrees C, 100% humidity and a 5% CO2 atmosphere for almost a month. The
      number of cells substantially increased to reach 12 millions for almost a month.
      The culture medium was changed every 3 days. The polymer tube that served as a
      scaffold for cells was composed of the copolymer of PCL-PLA (50:50) with
      reinforcement by woven PGA. The polymer conduit, 10 mm in diameter, 20 mm in
      length and 1 mm in thickness, was designated to biodegradate within 8 weeks. The
      number of seeded cells was approximately a million/cm2. The graft transplantation
      was performed 10 days after seeding cells. The occlusive right intermediate
      pulmonary artery was reconstructed with the TE vessel graft under extracorporeal
      circulation with a pump-oxygenator. The patient followed a satisfactory
      postoperative course. The postoperative angiography demonstrated that the graft
      was not constricted and dilated but that it preserved good patency. Long-term
      follow-up are necessary. We plan to continue to use the TE technique using
      autologous cells in the low pressure system like venous or pulmonary circulation.
      Because our results even in early experimental phase were valuable and promising,
      we believe that the TE approach may play an important role in the near future as
      an another alternative, together with transplantation and artificial organ,
      especially in the field of cardiovascular surgery that mostly needs replants.

PMID- 11995318
TI  - [Left atrial myxoma with extramedullary hematopoiesis and ossification].
AB  - A 65-year-old female with palpitation was referred to our hospital for a further
      examination. Trans-esophageal and thoracic echocardiogram demonstrated a left
      atrial tumor with a patchy calcification, arising from the lower portion of the
      interatrial septum. It was completely extirpated together with its sessile
      pedicle and the related disc of interatrial septum. The tumor showed the
      extensive extramedullary hematopoiesis and ossification around scanty clusters of
      myxoma cells on light microscopy. These findings indicated further support to the
      belief that the primitive mesenchymal cell is the origin in cardiac myxoma.

PMID- 11995319
TI  - [Experience with pyoktanin lavage for mediastinitis and prosthetic graft
      infection following thoracic aortic surgery].
AB  - Pyoktanin, a triphenylmethane dye, is known to have a potent bactericidal
      activity against Gram-positive bacteria including methicillin-resistant
      Staphylococcus aureus (MRSA). We used pyoktanin for irrigating wounds in 2 cases
      of mediastinitis and prosthetic graft infection following thoracic aortic
      surgery. Case 1 is mediastinitis and prosthetic graft infection due to
      Staphylococcus epidermidis following Cabrol procedure. After irrigating the
      anterior mediastinum with 0.1% pyoktanin solution twice a day for 8 days, omental
      transposition was performed, which let to cure of the infection. Case 2 is
      mediastinitis due to methicillin-resistant Staphylococcus epidermidis following
      ascending aortic and aortic arch replacement for acute type A aortic dissection.
      After irrigating the wound with 0.1% pyoktanin solution twice a day for 14 days,
      the wound was closed primarily, which resulted in cure of the infection of the
      wound. Using pyoktanin at low concentrations for irrigating wound for a short
      period of time is considered permissible and effective for mediastinitis and
      prosthetic graft infection due to Gram-positive bacteria including MRSA.

PMID- 11995320
TI  - [Surgery for intrathoracic recurrence and second primary tumors in resected lung
      cancer].
AB  - From 1986 to 2000, 42 patients (3.7%) underwent resection for intrathoracic
      recurrence or second primary lung cancer. Survival in 27 patients with recurrent
      diseases was 60% at 5 years and 35% at 10 years compared with 65% at 5 and 10
      years for 15 patients with metachronous lung cancers morphologically. Ten
      patients had the second operation less than 2 years since the first operation, 19
      patients between 2 and 5 years, and 13 patients more than 5 years, while these 5
      year survivals were 72%, 53%, 67% respectively. At the first operation lobectomy
      was performed in 39 patients (93%), wedge resection or segmentectomy in 3. The
      reoperation was 14 lobectomy or completion pneumonectomy, 24 wedge or
      segmentectomy (57%), and 4 other procedures, while these 5-year survivals were
      35%, 73%, and 100% respectively. The 5-year survival was 78% for 27 patients with
      stage I disease and 26% for 10 patients with stage III disease at the first
      operation, compared with 55% for 30 patients with stage I and 53% for 9 patients
      with stage III at the reoperation. These data suggest that limited resection is
      recommended for intrathoracic recurrent diseases and metachronous multiple lung
      cancers whenever possible.

PMID- 11995321
TI  - [Recurrent low output syndrome after the weaning from mechanical circulatory
      support for postcardiotomy cardiogenic shock].
AB  - We reviewed the cases of recurrent low output syndrome (LOS) after the weaning
      from mechanical circulatory support for postcardiotomy cardiogenic shock. Twelve
      patients were divide into 2 groups according to whether low output syndrome
      recurred or not, consisting of a recurrent low output syndrome (+) group [re-LOS
      (+) group, n = 6] and a recurrent low output syndrome (-) group [re-LOS (-)
      group, n = 6]. Between 2 groups, there was no statistical difference in
      preoperative left ventricular ejection fraction (LVEF), aortic closs-clamping
      time and cardiac index at the weaning from mechanical circulatory support. Only
      the LVEF at the weaning in the re-LOS (+) group was significantly less than that
      in the re-LOS (-) group (0.39 +/- 0.08 vs 0.62 +/- 0.19, p < 0.05). All patients
      in the re-LOS (-) group survived to discharge, while in the re-LOS (+) group,
      although 3 patients were re-supported by intra-aortic balloon pumping, 4 of 6
      patients died of multiple organ failure and 2 survivors were in New York Heart
      Association class III. The results suggest that the key to survive to discharge
      after the weaning from mechanical circulatory support is whether the cardiac
      contraction could recover or not.

PMID- 11995322
TI  - [Surgical angioplasty of isolated left coronary ostial stenosis].
AB  - A 42-year-old female had suffered from chest pain for approximately 1 month, and
      was admitted with unstable angina pectoris. Emergent coronary angiography showed
      an isolated 75% stenosis of the left coronary ostium. Repair of ostial stenosis
      by vein patch angioplasty was done by the transactional superior approach.
      Postoperative catheterization revealed an expanded left coronary orifice and the
      patient was discharged without any complications. We have experienced 2 other
      patients of isolated left coronary ostial stenosis, who had undergone double
      coronary artery bypass grafting. Long-term coronary angiography showed regression
      of ostial stenosis in 1 patient, and no progression of new lesions in either.
      These results suggest that direct vein patch angioplasty of the ostial lesion is
      an alternative procedure for isolated left coronary ostial stenosis.

PMID- 11995323
TI  - [Lateral femoral circumflex artery for coronary artery bypass surgery in a
      patient receiving hemodialysis: report of a case].
AB  - A 59-year-old man receiving hemodialysis had a 2-vessel coronary disease. We
      performed double coronary artery bypass grafting with the left internal thoracic
      artery to the left anterior descending artery, and the composite graft of right
      internal thoracic artery and lateral femoral circumflex artery to the right
      coronary artery. Postoperative coronary angiogram showed that the LFCA bypass
      graft was widely patent and supplied sufficient blood to the anastomosed vessel.
      There was no stenosis at the anastomotic site. He had no postoperative
      complication. Long-term follow-up and more cases is necessary to establish the
      usefulness of LFCA as an arterial free graft for coronary revascularization in
      patients receiving hemodialysis.

PMID- 11995324
TI  - [An elderly case of ruptured aortic arch aneurysm 3 years after coronary artery
      bypass grafting].
AB  - We reported a case of trans-aortic endovascular stent grafting (open stent
      method) for ruptured true aneurysm of the aortic arch. A 83-year-old female, who
      had suddenly complained back pain and been diagnosed as the ruptured aortic arch
      aneurysm by computer tomography, was admitted for an emergent surgery. We
      performed emergent trans-aortic endovascular stent grafting (open stent method).
      Postoperatively she had no complication and recovered uneventfully.

PMID- 11995325
TI  - [Concomitant lobectomy by video-assisted thoracic surgery and coronary artery
      bypass grafting: report of a case].
AB  - Successful simultaneous operation for cardiac and lung disease was performed in a
      71-year-old man with lung carcinoma and ischemic heart disease. Chest CT scan
      revealed a mass in the right lower lobe and absence of mediastinal
      lymphadenopathy. Coronary angiography revealed significant stenosis of the left
      anterior descending artery, circumflex artery and right coronary artery. We
      performed concomitant video-assisted right lower lobectomy with mediastinal lymph
      node dissection as a form of less invasive surgery and triple coronary artery
      bypass grafting under cardiopulmonary bypass. Curative surgery for lung carcinoma
      and complete revascularization for ischemic heart disease were completed. The
      postoperative course was uneventful.

PMID- 11995326
TI  - [Off-pump coronary artery bypass grafting via a left thoracotomy in a patient
      with left main trunk disease].
AB  - We report a case of multiple coronary artery bypass grafting (CABG) via a left
      thoracotomy without cardiopulmonary bypass. A 54-year-old female with unstable
      angina pectoris associated with left main trunk disease underwent emergency CABG.
      Because the patient had a history of total arch and aortic root replacement due
      to type A aortic dissection, a left thoracotomy approach was selected. The
      proximal end of the Y-shaped saphenous vein graft was anastomosed to the left
      subclavian artery, rather than to the descending aorta, owing to the remaining
      aortic dissection. The distal end of the Y-shaped saphenous vein graft was
      anastomosed to the left anterior descending artery and the posterolateral branch
      without cardiopulmonary bypass. The postoperative course was uneventful. The
      results of this surgery seem to indicate that off-pump CABG via a left
      thoracotomy is a viable technique, especially for patients undergoing repeat
      CABG.

PMID- 11995327
TI  - [An elderly case with impending myocardial infarction of endoventricular circular
      patch plasty with coronary artery bypass grafting].
AB  - An 81-year-old man with anterior impending re-myocardial infarction was urgently
      operated. Preoperative ECG and UCG examinations showed old myocardial infarction
      and LV aneurysm, respectively. We chose the Dor method (endoventricular circular
      patch plasty) and CABG aiming at early recovery from congestive heart failure. He
      fell into respiratory failure temporarily, but otherwise, the clinical course of
      this operation was good. He was discharged 47 days after the operation on foot.
      The Dor method combined with CABG is excellent way to relieve patients from
      congestive heart failure with LV aneurysm.

PMID- 11995328
TI  - [Thoracic outlet syndrome with arterial complication treated by the subclavicular
      transsternal approach: report of a case].
AB  - A 42-year-old female was referred to our vascular service because of her right
      arm fatigue and cold sensitivity. On elevation of right arm, her radial pulse was
      absent with pallor of the hand. Angiography demonstrated a significant stenosis
      of the right subclavian artery, which was considered to be complication of
      thoracic outlet syndrome. We performed resection of the first rib using the
      standard subclavicular approach and the subclavian-subclavian artery bypass using
      a new transsternal extension approach to the subclavian artery. After follow-up
      18 months, she was working and asymptomatic. This transsternal extension is
      effective to treat the arterial complication after decompression of the thoracic
      outlet.

PMID- 11995329
TI  - [Subglottic granuloma with extubating mini-trach II: report of a case].
AB  - A case of subglottic granuloma after extubating Mini-trach II is described. The
      patient went aorto-coronary bypass and Mini-trach II was inserted for suction of
      sputum. Mini-trach II was extubated 6 days after insertion. The patient
      complained of dyspnea 3 months later. Examination showed subglottic granuloma.
      First, we burned the granuloma by laser under local anesthesia. Because the
      visual field was not good due to vocal cord movement, we failed to resect the
      granuloma completely. Therefore, we performed laryngo microsurgery under general
      anesthesia and resected the granuloma perfectly. The patient is in good health
      without signs of recurrence 6 months after granuloma removal. When we used Mini
      trach II, the most important issues are insertion to the cricothyroid membrane,
      preventing infection, and careful follow-up after removing the Mini-trach II.

PMID- 11995330
TI  - [Cardiac sarcoidosis diagnosed by thoracoscopically resected lung nodule: report
      of a case].
AB  - A 71-year-old woman was admitted to our hospital with general fatigue and
      dyspnea. Emergency pacemaker implantation was performed after diagnosis of
      complete AV block. After 1 month, a small lung nodule, which had been 10 mm in
      diameter 1 year ago, was revealed to have grown to 15 mm in diameter by CT scan.
      Thoracoscopical resection of the lung nodule resulted in sarcoidosis. Abnormality
      in the posteroinferior heart was detected by 99mTC-PYP myocardial perfusion
      scintigraphy and it was diagnosed as cardiac sarcoidosis.

PMID- 11995331
TI  - [Two views of protein folding: what is the universal view?].

PMID- 11995332
TI  - [Amyloid fibril formation of beta 2-microglobulin].

PMID- 11995333
TI  - [Studies on dynamics of protein folding/unfolding by using the laser-induced
      temperature jump technique].

PMID- 11995334
TI  - [Molecular evolution and folding mechanism of proteins].

PMID- 11995335
TI  - [Protein folding funnel and dynamical function].

PMID- 11995336
TI  - [Mechanical unfolding of proteins by forced stretching].

PMID- 11995337
TI  - [Molecular mechanism of self-incompatibility in Brassica].

PMID- 11995338
TI  - [Structural homology between molecular probes binding site of DNA polymerase beta
      and DNA topoisomerase II].

PMID- 11995339
TI  - [Tailor-made ES-like cells for regenerative therapy by ES-somatic cell fusion].

PMID- 11995340
TI  - [Deposition with DNA Date Bank of Japan (DDBJ); its data format and tools for
      submitions].

PMID- 11995341
TI  - [Deposition with the Protein Data Bank].

PMID- 11995342
TI  - [Chronic cervical and lumbar epidural catheterization through the atlanto
      occipital membrane in rats].
AB  - We report here an efficient means of epidural catheter placement through atlanto
      occipital membrane in rats. METHODS: Male SD rats (n = 84) were divided into
      lumbar (n = 48) and cervical (n = 36) groups. Under sterile technique, PVC V-1
      tubing was inserted and advanced caudally targeted to the C 4 or L 4 level.
      Analgesic efficacy and duration were measured by injecting increments of 2%
      lidocaine until a maximum paw withdrawal latency time from a radiant heat thermal
      stimulator. Rats (n = 6 each day) were sacrificed and an autopsy was performed to
      observe both the laterality of the catheter tip and the proliferation of fibrous
      tissue around the catheter. RESULTS: The volume of lidocaine and its duration was
      52 +/- 17 microliters and 27 +/- 13 min (mean +/- SD) in lumbar, 30 +/- 10
      microliters and 26 +/- 9 min in cervical group. In lumbar group, two catheters
      penetrated the dura. The remaining catheters were confirmed to be in the epidural
      space within L 4 +/- 1 or C 4 +/- 2 segment. Lumbar catheter tips were almost
      equally distributed between the center, left and right, while cervical catheter
      tips were distributed between left and center portion of the epidural space. The
      severity of tissue proliferation was time dependent. The proliferation of
      fibrotic tissue seemed more rapid in cervical than lumbar group. CONCLUSION:
      Although this approach for epidural catheter placement is efficient and produces
      excellent drug effects on day 3 after implantation, as reported by others, rapid
      development of fibrous tissue around the catheter quickly limits the usefulness
      of the epidural catheter.

PMID- 11995343
TI  - [The effects of intrathecally administered baclofen on somato-sympathetic reflex
      potentials].
AB  - We investigated the antinociceptive effect of intrathecally administered S(-)
      baclofen and R (+)-baclofen in cats using somato-sympathetic reflex potentials
      derived from lumbar sympathetic ganglion by stimulation of the femoral nerve. S(
      )-baclofen 10 mg maximally reduced both A reflex potential and C reflex potential
      to 65.3% and 83.7% of control values, respectively, 1 minute after the
      administration, but these changes were not significant. The inhibition of A
      reflex potential at this dosage was greater than that of blood pressure and heart
      rate induced by the same dosage of S(-)-baclofen. While, R(+)-baclofen 1 mg
      maximally inhibited A reflex potential to 48.6% of control value 20 minutes after
      the administration, and this change was significant (P < 0.05). The inhibition of
      A reflex potential was greater than that of blood pressure and heart rate induced
      by the same dosage of R(+)-baclofen. This dosage of baclofen reduced C reflex
      potential to 66.4% of control value 10 minutes after the administration. The
      degree of reduction of A and C reflex potentials induced by 1 mg of R(+)-baclofen
      was higher in comparison with that induced by 10 mg of S(-)-baclofen. These
      reduction of A and C reflex potentials were reversed by 1 to 1.5 mg of
      intrathecally administered saclofen. These results indicate that R(+)-baclofen
      has higher potency than S(-)-baclofen and suggest that S(-)-baclofen and R(+)
      baclofen show antinociceptive effect by intrathecal administration. On the other
      hand, it is possible that these two drugs exert antinociceptive effect via A
      delta fiber.

PMID- 11995344
TI  - [Effect of prostaglandin E1 infusion during and after total hip arthroplasty
      under hypotensive anesthesia on postoperative liver function and hemorrhage].
AB  - We evaluated the effects of prostaglandin E1 (PGE1) on the liver function and
      hemorrhage after total hip arthroplasty (THA). Twenty patients with normal liver
      function were randomly divided into two groups. The patients were anesthetized
      with spinal anesthesia using 0.5% bupivacaine 4 ml and epidural anesthesia. The
      laryngeal mask was inserted after administrations of 1.5-2 mg.kg-1 of propofol
      and 0.8 mg.kg-1 of succinylcholine. PGE1 was infused in the PGE1 group at a rate
      of 0.01 microgram.kg-1.min-1 (PGE1 group) during and after the operation (30-40
      hrs). GOT and GPT values were evaluated before, and at the end of operation, and
      on 1, 4 and 7 postoperative days in each group. The amount of hemorrhage was
      measured at the end of operation and on 1, 2, 3 and 4 postoperative days in each
      group. GOT values on 1 and 4 postoperative days in PGE1 group were significantly
      lower than those in the control group. GPT values on 1, 4 and 7 postoperative
      days in PGE1 group were also significantly lower than those in the control group.
      The amount of bleeding during the operation and postoperative hemorrhage did not
      differ significantly between the two groups. These results suggest that PGE1 may
      prevent postoperative liver damage, but it may not affect the amount of
      postoperative bleeding.

PMID- 11995345
TI  - [Assessment of preoperative anxiety in patients entering the operating room on
      foot using state-trait anxiety inventory].
AB  - The purpose of this prospective study was to assess the effect of walking into
      the operating room on preoperative anxiety level. Sixty non-premedicated patients
      scheduled for elective surgery were randomly divided into two groups based on how
      they were transported into the operating room. One group was carried on a
      stretcher (n = 30) and the other entered on foot under their own power (n = 30).
      A subjective assessment of anxiety was performed using a state-trait anxiety
      inventory (STAI) the day before surgery and on arrival at the operating room.
      STAI values were not increased in the operating room as compared to the day
      before surgery for either group and did not differ between groups, though they
      showed a high level of anxiety throughout the preoperative period. We conclude
      that walking into the operating room has no significant influence on preoperative
      anxiety level.

PMID- 11995346
TI  - [Effects of vascular injuries on hemostatic abnormalities in prolonged surgeries
      of maxillofacial malignant cancer].
AB  - We evaluated the effects of surgical invasion and vascular injury on hemostatic
      abnormalities in seventeen ASA I-II patients undergoing prolonged surgeries of
      eight hours or more consisting of tumor excision, radical neck dissection and
      free flap reconstruction in the maxillofacial region. As molecular markers of
      blood coagulation and surgical invasion, prothrombin fragment 1 + 2 (F 1 + 2),
      interleukin-6 (IL-6), tissue-type plasminogen activator (tPA), thrombomodulin
      (TM) and plasmin alpha 2-plasmin inhibitor complex (PIC) were measured during
      surgery and on the first and second postoperative days. The F 1 + 2 values
      increased significantly during surgery and decreased postoperatively, and reached
      the maximum at the end of surgery. Changes in IL-6 and tPA were similar to those
      of F 1 + 2, and there was a correlation in the levels of F 1 + 2 and IL-6 (r =
      0.54), tPA (0.41) and PIC (0.30) at each measurement time. PIC and TM, however,
      did not show statistically significant changes intra- and postoperatively, nor
      was there any correlation between F 1 + 2 and TM values. From these results, we
      conclude that inflammatory mediators and endothelial stimulation activated by
      surgical invasion may influence hypercoagulability. Vascular injury, however, did
      not act as the main coagulation factor during prolonged maxillofacial surgery.

PMID- 11995348
TI  - [Usefulness of epidural nerve stimulation to confirm epidural catheter
      placement].
AB  - An epidural catheter must be placed in epidural space correctly to give
      sufficient epidural anesthesia for patients. Recently, as a technique to confirm
      the catheter placement, electrical stimulation of epidural nerve using an
      inserted epidural catheter was introduced. This study was conducted to evaluate
      the reliability of this simple technique in 13 patients. Immediately after an
      epidural catheter (19 G Arrow Flextip Plus) was placed, an adapter with electrode
      (Arrow-Johans ECG Adapter) was attached to its connector and nerve stimulation
      was performed using a peripheral nerve stimulator (1 Hz, 10 mA). Catheter
      placement was judged to be correct by both presence of muscle contraction in
      response to stimulation and occurrence of analgesia after the administration of a
      local anesthetic. In 5 patients, additional roentgen examinations were performed
      to identify the positions of catheters. In all patients except one, muscle
      contraction was observed by stimulation, and analgesia was confirmed in all
      patients after the injection of an anesthetic. X-ray examinations revealed that
      the tip of catheter placed at the vertebral level corresponded with the spinal
      segmental level where muscle movement occurred. Our study demonstrates that nerve
      stimulation can be a reliable method to confirm epidural catheter placement. Our
      results also suggest that the position of catheter tip can be estimated easily
      using this technique.

PMID- 11995347
TI  - [Bispectral index monitoring is useful to reduce total amount of propofol and to
      obtain immediate recovery after propofol anesthesia].
AB  - Bispectral index (BIS) is a processed EEG parameter for assessment of hypnotic
      effects of anesthetics. We studied whether BIS monitoring can improve recovery
      from propofol anesthesia and decrease the total amount of propofol needed. Forty
      six patients without hypertension and obesity were studied. In the BIS group (n =
      20), propofol infusion rate was adjusted to achieve a target BIS value between 40
      60, increasing to 65 during the final 10 min of the surgical procedure. In the
      control group (n = 19), propofol infusion rate was adjusted based only on
      standard clinical signs. Compared with the control group, patients in the BIS
      group required lower propofol infusion rates(4.3 +/- 1.1 vs 4.9 +/- 0.8 mg.kg-1.h
      1; P < 0.05), and the total amount of propofol decreased significantly (709 +/-
      210 vs 914 +/- 326 mg; P < 0.05). BIS monitoring led to immediate recovery after
      propofol anesthesia. There were no significant differences in the incidence of
      intraoperative responses between the two groups. BIS monitoring decreased the
      total amount of propofol and led to immediate recovery after propofol anesthesia.
      These findings indicate that the use of BIS monitoring may be useful in
      controlling the infusion rate of propofol during surgery.

PMID- 11995349
TI  - [Is local anesthesia necessary for venipuncture?].
AB  - We evaluated the necessity of local anesthesia for the venipuncture pain in 27
      healthy adult volunteers by using a visual analogue scale (VAS) from 0 to 10. The
      pain scales were measured three times: at the time of percutaneous intravenous
      cannulation (20 G polyurethane catheter) without local anesthesia as well as the
      skin infiltration with local anesthetics (0.5% lidocaine 0.5 ml; 25 G needle),
      and after intravenous cannulation. The measurements were done twice, once by an
      expert staff and once by a novice staff with an interval of three days. VAS
      values were significantly higher (2.4 +/- 1.1) for the percutaneous intravenous
      cannulation without local anesthesia than both for the skin infiltration with
      local anesthetics (1.4 +/- 0.6) and for the evaluation after intravenous
      cannulation (0.7 +/- 0.8), independent of who inserted the catheter. VAS values
      were significantly lower (2.1 +/- 1.0) when the percutaneous intravenous
      cannulation without local anesthesia was performed by expert staff than when it
      was performed by novice staff (2.7 +/- 1.1; P < 0.05). We conclude that local
      anesthesia is necessary when novice staff performs the percutaneous intravenous
      catheterization.

PMID- 11995350
TI  - Neoadjuvant chemotherapy prior to radical operation as a risk factor for
      nocturnal oxygen desaturation in perioperative periods.

PMID- 11995351
TI  - [Vital capacity rapid inhalation induction (VCRII) technique with sevoflurane for
      a rheumatoid patient with difficult airway].
AB  - Successful airway management in an adult female patient with limited cervical
      extension and a subluxation of bilateral jaw joints caused by rheumatoid
      arthritis was reported. We planned to reduce the intensity of pain in her right
      hand through neurolysis of the ulnar nerve in her right elbow joint. Right
      axillary nerve blockade with 1% lidocaine 10 ml and 0.25% bupivacaine 10 ml, was
      employed unsuccessfully to achieve adequate anesthetic effect. Anesthesia was
      administered using a vital capacity rapid inhalation induction (VCRII) technique
      with 5% sevoflurane in the oxygen. When the patient lost consciousness, a size 3
      laryngeal mask airway (LMA) was inserted under spontaneous breathing on the first
      trial. There was very little hemodynamic change during the insertion of the LMA.
      Anesthesia was maintained with sevoflurane 1.5-2.0% in oxygen under spontaneous
      breathing. Emergence from anesthesia was rapid and no signs of upper airway
      obstruction were observed after the removal of the LMA. The use of the LMA with
      VCRII technique and anesthetic maintenance using sevoflurane, are likely to be an
      optional technique of airway management in patients with problematic airway.

PMID- 11995352
TI  - [A case of AV block (Mobitz II type) during recovery from general anesthesia
      combined with epidural anesthesia].
AB  - A 59-year-old female underwent total hysterectomy for cancer of the corpus uteri.
      Epidural catheterization was performed at T 12/L 1 interspace. Anesthesia was
      induced with propofol (80 mg) and vecuronium (6 mg) and maintained with nitrous
      oxide (66%) and sevoflurane (0.8-1.5%) in oxygen. Six ml of 1.5% lidocaine
      containing 1: 200,000 epinephrine was injected intermittently through the
      epidural catheter for epidural anesthesia. Surgery was performed uneventfully.
      During her recovery from anesthesia, Mobitz II heart blocks and bradycardia were
      observed when the discharge in the oral cavity was aspirated. The AV blocks
      disappeared within 2 min, but similar arrhythmia was observed when the discharge
      in the oral cavity was aspirated again. Stimulation of the trachea by a suction
      drainage reversed the arrhythmia to the normal sinus rhythm. The trachea was
      extubated, and arrhyththmia was no longer observed in the operating room, but
      when the patient vomited, the next morning, bradycardia occurred and she lost
      consciousness. Two weeks later, there were no abnormal findings in
      echocardiography, Holter ECG, master-double ECG, and scintigraphy of the heart.
      It is likely that in this patient stimulation of the oral cavity by suction
      drainage and vomiting triggered vagovagal reflex, causing the AV block.

PMID- 11995353
TI  - [Drug-induced side effects in a patient with status asthmaticus treated with long
      term isoflurane inhalation].
AB  - We describe a 23 year-old woman with status asthmaticus who was treated with long
      term isoflurane inhalation. In this case, we experienced severe drug-induced side
      effects. We conclude that isoflurane has low metabolic rate and may be the best
      alternative in the treatment of status asthmaticus. In long-term treatment, we
      have to take care of drug overdosing to avoid side effects.

PMID- 11995354
TI  - [Anesthetic management of a child with dilated cardiomyopathy associated with
      congenital fiber-type disproportion].
AB  - A 3-year-old girl, who presented with dilated cardiomyopathy in conjunction with
      congenital fiber-type disproportion, underwent open reduction for congenital
      dislocation of the hip. Preoperative echocardiography demonstrated left
      ventricular dilatation with an ejection fraction (EF) of 0.33. Anesthesia was
      induced with intravenous ketamine and fentanyl, and maintained with fentanyl
      administered incrementally to a total dose of 10 micrograms.kg-1 and 1-1.5%
      isoflurane. During operation, we continuously monitored left ventricular wall
      motion and measured left ventricular diastolic dimension (LVDd), systolic
      dimension (LVDs), cardiac output (CO), EF, and fractional shortening (FS) with
      transesophageal echocardiography (TEE). At the end of surgery, preload (LVDd) and
      LV contractility (CO, EF, FS) decreased, but LV wall motion remained almost
      stable throughout the procedure. In conclusion, TEE was useful for intraoperative
      management of a child with dilated cardiomyopathy.

PMID- 11995355
TI  - [Survey of preoperative cardiology consultation].
AB  - Cardiology consultations are often requested preoperatively for patients with
      cardiovascular problems. However, there are frequently differences in the
      evaluation of preoperative cardiac risks among cardiologists, surgeons and
      anesthesiologists. In order to obtain possible solutions to this problem, we
      conducted a survey of preoperative cardiology consultations performed directly by
      cardiologists. The survey indicates a lack of interaction with anesthesiologists
      and insufficient information on the surgical procedures and anesthesia for
      cardiologists to assess compromising cardiac risks. In addition, many
      cardiologists suggested that exercise tolerance required for surgical procedures
      should be 7 METs or more for surgical patients.

PMID- 11995356
TI  - [A simple method for determination of flurbiprofen in human plasma by gas
      chromatography-mass spectrometry].
AB  - A method for gas chromatograph-mass spectrometric assay has been developed for
      the quantitation of flurbiprofen in human plasma. Extraction or condensing
      procedure was not required and the method reduced time involved in sample
      preparation. The analytes were separated on the fused-silica capillary column.
      The operating conditions were: injector, 250 degrees C; detector, 300 degrees C;
      and column, 50-280 degrees C. The total gas flow-rate of helium (carrier) was 50
      ml.min-1 and the pressure of column inlet was 100-200 kPa. The retention time was
      18.1 min and the limit of quantitation was 0.5 microgram.ml-1. This method
      provides an easy and simple method for the detection of flurbiprofen.

PMID- 11995357
TI  - [Clinical use of the VIA Blood Gas Monitor System].
AB  - VIA Blood Gas Monitor System (Baxter) withdrawals and reinforces blood
      automatically and measures pH, PaCO2, PaO2, sodium, potassium, and hematocrit. We
      evaluated VIA for use during cardiopulmonary bypass in 8 patients and during
      differential lung ventilation in 6 patients. The bias and precision were
      calculated on all the measured parameters. A total of 127 blood samples were
      obtained for comparison. Blood gas data measured by VIA were clinically
      acceptable except sodium. These findings suggest that VIA is useful for the
      management of patients in whom frequent arterial gas measurements are necessary.

PMID- 11995358
TI  - Azathioprine side effects in the treatment of chronic inflammatory bowel disease.

PMID- 11995359
TI  - Adverse effects of azathioprine in the treatment of inflammatory bowel disease.
AB  - OBJECTIVE: To know the type, frequency and time course for the occurrence of
      adverse events in our series of patients with inflammatory bowel disease treated
      with azathioprine or 6-mercaptopurine. PATIENTS AND METHOD: 92 consecutive
      patients were treated with azathioprine. 70 of them (55 Crohn's disease, 14
      ulcerative colitis and 1 undetermined colitis) were suitable for analysis.
      RESULTS: We observed 23 adverse reactions in 21 patients. Adverse events were as
      follows: haematological 11.4%, digestive intolerance 11.4%, infection 7.1%, and
      pancreatitis 2.8%. The prevalence was increased among ulcerative colitis patients
      (57.8 vs. 21.8%) (p = 0.02). There were no statistical differences in the
      prevalence of adverse events respective of the age, gender or location of
      disease. Digestive intolerance and pancreatitis occurred within the first 6
      months of therapy, whereas haematological side effects occurred between 3 months
      and 4 years after therapy onset. Early occurrence (but not late occurrence) was
      associated with thiopurine methyltransferase (TMPT) activity levels. All
      infections took place between 8 months and 5 years of treatment. Azathioprine was
      definitively withdrawn due to side effects in 9 cases (12.8%). CONCLUSIONS: The
      frequency of adverse events in our study is similar to that reported in previous
      studies. Azathioprine withdrawal is required in almost half of the cases because
      of toxicity. Frequency of side effects is increased in patients with ulcerative
      colitis. The variability in time course makes clinical-biological monitoring
      mandatory.

PMID- 11995360
TI  - Relation between the bowel electromyogram and the intestinal pressure wave. An
      experimental study in dogs.
AB  - OBJECTIVE: A linear regression study is made of the parameters identifying the
      electrical activity of the small bowel, with the aim of determining those
      variables most closely related to the type I pressure waves. PATIENTS AND
      METHODS: A computer system was used for the simultaneous and real time
      acquisition of the manometric activity (using microballoons implanted in the
      bowel mucosa) and electromyogram of the intestine (employing bipolar electrodes
      implanted in the intestinal serosa) in dogs. RESULTS: Of the electromyogram
      intestinal parameters studied, those determining signal energy (root mean square
      voltage and energy) yielded the highest correlation coefficients (0.71 +/- 0.08
      in the jejunum and 0.78 +/- 0.06 in the duodenum) to bowel pressure. Peak-to-peak
      voltage also shows good correlation, though to a lesser degree. The rest of the
      parameters studied, such as those that measure the duration of the action
      potential or its number of peaks, yielded poor correlations to pressure.
      CONCLUSIONS: It is concluded that the energy of the intestinal electromyogram
      represents the mechanical activity of the small bowel, reflecting intestinal
      motility, and that the recording of this parameter is not subjected to subjective
      cutoff values or threshold levels. On the other hand, and unlike in the case of
      manometric recordings, the signal obtained is free of background interference and
      noise.

PMID- 11995361
TI  - Cytochrome oxidase activity in splanchnic organs of portal hypertensive rats.
AB  - OBJECTIVE: Portal hypertension is characterized by hyperdynamic splanchnic
      circulation associated with the development of portosystemic portal collateral
      circulation. Since blood flow regulation mechanisms in the splanchnic organs can
      be metabolic, its metabolic capacity has been studied using the mitochondrial
      enzyme cytochrome C oxidase as histochemical marker. METHOD: Cytochrome oxidase
      was quantified with a histochemical technique in the liver, pancreas and small
      bowel of Wistar rats in the control group (n = 8) and in rats with portal
      hypertension by triple stenosing ligation of the portal vein (n = 9) at 28 days
      of evolution. RESULTS: All rats with portal hypertension develop portosystemic
      collateral circulation. In these animals, cytochrome oxidase activity increases
      (p < 0.01) in the liver (left lateral lobe, periportal zone: 91.81 +/- 5.18 vs.
      86.03 +/- 2.82) exocrine pancreas (125.6 +/- 7.25 vs 117.57 +/- 6.43; p < 0.05)
      as well as in the mucosa (crypts) and duodenum serosa, jejunum and ileum while it
      decreases in the pericentral zone of the hepatic acinus and intestinal villi.
      CONCLUSION: Cytochrome oxidase is considered an endogenous marker of local
      tissular metabolic capacity, so that its increased activity in the small bowel
      mucosa, crypts, exocrine pancreas and visceral peritoneum may be a metabolic
      factor that induces splanchnic hyperdynamic circulation in short-term portal
      hypertensive rats.

PMID- 11995362
TI  - Long-term management of GERD. Why using endoscopy just now?
AB  - Early results with the use of endoscopic techniques in the treatment of gastro
      oesophageal reflux disease (GERD) have been recently reported. Methods used are
      an injection of biocompatible substances within the lower oesophageal sphincter
      (LES), LES ablation using radio-frequency, and suture of folds in the area distal
      to the Z-line. The latter--endoscopic gastroplasty--is most difficult, but this
      technique has been most widely accepted by gastroenterologists to this date.
      Effectiveness of these endoscopic management systems in the long-term control of
      GERD has never been compared to a control group. This fact, together with the
      proven efficacy of anti-secretory drugs and the refinement of laparoscopic
      surgery during the past few years, has led physicians to be more demanding
      regarding early results. This review will discuss each method available, and
      issues answered by reported studies to this day are approached.

PMID- 11995363
TI  - [Herpetic ulcerative esophagitis in immunocompetent patient].

PMID- 11995364
TI  - [Selective COX-2 non-steroidal anti-inflammatory agents and gastrointestinal
      toxicity].

PMID- 11995365
TI  - [Prolonged permanence of foreign body in the esophagus].

PMID- 11995366
TI  - [Acute cholestatic hepatitis probably caused by sertraline].

PMID- 11995367
TI  - [Foreign body ingestion: a unique case].

PMID- 11995368
TI  - Measuring quality of life in Spain.

PMID- 11995369
TI  - Translation and validation of the gastrointestinal Quality of Life Index (GIQLI).
AB  - OBJECTIVE: To translate into Spanish and validate the GIQLI, a health related
      quality of life questionnaire for gastrointestinal diseases. PATIENTS AND
      METHODS: All patients with a diagnosis of cholelithiasis, on waiting list to
      undergo a cholecystectomy, from three public hospitals, were included in this
      study. All patients were requested to fulfill the GIQLI and the SF-36 before and
      three months after the intervention. The validity, reliability and responsiveness
      of the GIQLI were studied. RESULTS: 353 patients completed both questionnaires
      before and after the intervention. The GIQLI was able to discriminate among
      levels of severity, measured by the number of previous biliary colics, between
      those with less (total GIQLI score: 102.7) or more than 6 colics (89.2). GIQLI
      domains correlated with those of the SF-36 (Pearson correlation coefficient from
      0.58 to 0.79). Internal consistency of its domains was good (Cronbach alpha from
      0.70 to 0.86). Responsiveness, measured by the standardized response mean, of the
      GIQLI ranged between 0.45 to 0.82, better than the generic questionnaire SF-36
      (0.20 a 0.56). CONCLUSIONS: GIQLI translation into Spanish provides with a new
      tool to measure quality of life on gastrointestinal diseases. Our results support
      the validity, reliability and responsiveness of the GIQLI Spanish version.

PMID- 11995370
TI  - Prevalence of coeliac disease in unexplained chronic hypertransaminasemia.
AB  - OBJECTIVE: To determine the prevalence of coeliac disease amongst the population
      with unexplained chronic hypertransaminasemia in our region. PATIENTS AND
      METHODS: A prospective study was carried out on 147 consecutive patients with
      chronic hypertransaminasemia, having previously discarded alcoholic cause,
      hepatotoxic drugs, B, C and Delta viral infections, autoimmune hepatitis, primary
      biliary cirrhosis, Jemochromatosis, alfal-antitrypsin deficiency, Wilson's
      disease, congestive liver and illicit drug use. Serum Ig A to gliadin and
      endomysium antibodies were determined. Intestinal biopsy was carried out in cases
      those positive for one or both antibodies. RESULTS: One patient was positive for
      both IgA to gliadin and to endonisyum antibodies, whereas another three patients
      were positive to IgA to gliadin only. A duodenal biopsy proved normal in two, a
      total villous atrophy in one and subtotal atrophy in other. CONCLUSIONS: 1. The
      prevalence of coeliac disease amongst the population with unexplained chronic
      hypertransaminasemia in our region is 1.4%. 2. In our region, screening for
      coeliac disease in unexplained chronic hypransaminasemia should take a secondary
      place.

PMID- 11995371
TI  - Treatment of cholecystoduodenal fistula in the era of laparoscopy.
AB  - INTRODUCTION: At first, laparoscopic cholecystectomy was considered unsuitable
      for patients presenting biliary tract diseases. This study seeks to demonstrate
      cholecystoduodenal fistula is not a contraindication for laparoscopic
      cholecystectomy, and it can be performed without a higher risk for the patient.
      PATIENTS AND METHODS: A retrospective study has been completed on laparoscopic
      biliary pathology from 1992 to 1999 (191 urgent and 877 elective choice
      surgeries). 302 cases (28%) are of complicated biliary pathology. We report on 14
      cholecystoduodenal fistulae, 3 cholecystocolonic fistulae, and 2
      cholecystogastric fistulae. RESULTS: Only in 5 patients with cholecystoduodenal
      fistula was the operation successfully completed by laparoscopy. Conversion to
      open surgery was because of bleeding (5 cases), difficulty for colon suture (2
      cases), and inflammation of the gallbladder with the duodenum (7 cases). An endo
      GIA 35 was used to transect the fistula. All patients were discharged after 4 or
      5 days without wound infection, and they have been evaluated at 3 and 12 months,
      without problems. CONCLUSION: Cholecystoduodenal fistula can no longer be
      considered a contraindication for laparoscopic treatment, and it does not
      increase morbidity risk.

PMID- 11995372
TI  - Relevance of the innate immune system.

PMID- 11995373
TI  - [Visceral leishmaniasis with duodenal involvement in an HIV patient].

PMID- 11995374
TI  - [Abdominal cystic lymphangioma].

PMID- 11995375
TI  - [Rectal-anal traumatic lesion].

PMID- 11995376
TI  - [Acute acalculous cholecystitis associated with leptospirosis].

PMID- 11995377
TI  - [Endoscopic argon plasma therapy for esophageal hemorrhagic lesions].

PMID- 11995378
TI  - [Efficacy of treatment of acute idiopathic facial paralysis, from "probable" to
      "possible"].

PMID- 11995379
TI  - [Heart failure today].

PMID- 11995380
TI  - [The Perruce decree, an opportunity to question the acceptance of a handicap and
      the relationship between physicians, justice and society].
AB  - The 'Perruche' decree (confirmed by the Paris Court of Cassation in November
      2001) recognizes the right of those born with a handicap to claim for
      compensation. However, there is a fear that this decree might lead to deviations
      in the requests submitted for systematic compensation, simply because of a
      handicap or prejudice, even in the absence of a medical error. The interest of
      the 'Perruche' decree is that it once again raises the question of the management
      of handicapped people in our society and the lack of sufficient help from the
      State. The decree also emphasizes the strong subjacent risk that a handicap could
      be considered as a failure or a medical error. The excessive ideology of a
      'perfect' child may therefore provoke the reject of the idea that a human being
      may be born with a deficiency or "imperfection". It also reminds us that medical
      practice remains exposed to errors and incertitude and that a zero risk does not
      exist, contrary to certain fantastical beliefs fostered by the principle of
      precaution. The hazard may correspond to the notion of incertitude. But it must
      not be confused with an error and it implies that which is unforeseeable. It is
      important that physicians stall the faith in the power of ultramodern techniques.
      Conversely, they should not claim a right to systematic error, when errors in
      fact hide authentic faults. The medical discourse must therefore remain
      responsible.

PMID- 11995381
TI  - [Development over 3 years of asthma recently diagnosed in a cohort of children
      (ASMA study). Factors related to improvement in clinical status].
AB  - OBJECTIVE: The objective of the ASMA study was to describe the evolution of light
      to moderate asthma, newly or recently (12 Pounds months) diagnosed in private
      pneumology centers, and to search for the predictive factors. METHODS: In 1995,
      251 private pneumologists, throughout Metropolitan France, recruited 396
      asthmatic children, 6 to 12 years old (64% boys). The 334 patients eligible for
      the study were examined every 4 months during 3 years (a mean of 6 controls were
      conducted out of the expected 9). The data were collected on standardized
      questionnaires completed by the physicians and notebooks filled-in by the
      patients the week before each control. This questionnaire comprised two asthma
      'control' criteria: "control" of the clinical state, defined as asthma attacks <
      1 per week AND nocturnal awakening < 1 per week AND absence of asthma symptoms
      between attacks on every control visit; "control" of the need for b2 mimetics on
      request, defined as the non-use throughout the week preceding the control visit.
      RESULTS: The global clinical state of the cohort rapidly improved once care was
      initiated: the proportion of children exhibiting at least one attack of asthma
      per week rapidly dropped to 43% on inclusion and to 13% on the first control
      visit (4 months), 10% on the second control visit, and then fluctuated at around
      8% up until the last control visit. A similar evolution was noted regarding
      nocturnal asthma attacks. The proportion of patients with prescriptions for
      inhaled corticosteroids and long-lasting b2-mimetics increased over the three
      years of follow-up. Analysis of the factors related to the individual 'control'
      of the clinical state showed a negative effect in family histories of asthma
      (father) and the presence of smokers in the home, but above all a positive effect
      of compliance to treatment and particularly its understanding (OR = 2.5; p =
      0.03) and respect of the doses (OR = 2.7; p < 0.01). The positive effect of
      compliance was confirmed by analysis of the factors related to the use of b2
      mimetics on request. CONCLUSION: Smoking should be avoided in the home.
      Compliance to treatment could be improved by making sure that the patients and
      their parents fully understand the disease and its treatment, and by persuading
      them to strictly follow the treatments prescribed.

PMID- 11995382
TI  - [Cyclothymic obsessive-compulsive disorder. Clinical characteristics of a
      neglected and under-recognized entity].
AB  - OBJECTIVE: Clinical research is largely focused on depressive comorbidity in
      obsessional compulsive disorder (OCD). However some recent publications have
      suggested that bipolar comorbidity occurs in authentic OCD and its presence has a
      differential impact on the clinical picture and course of OCD. METHOD: Recent
      data from the collaborative survey conducted with AFTOC (French Association of
      patients suffering from OCD) have revealed a high rate of bipolar comorbidity in
      OCD: 30% for hypomania and 50% for cyclothymia. RESULTS: The present paper
      presents further comparative analyses between OCD with (n = 302) versus without
      cyclothymia (n = 272). The sub-group "Cyclothymic OCD" is characterized by a
      different clinical picture (higher frequency of aggressive, impulsive, religious
      and sexual obsessions, and compulsions of control, hoarding, repetition),
      episodic course, higher rate of major depressive episodes (with more intensity
      and recurrence) associated with higher rates of suicide attempts and psychiatric
      admissions, and less favorable response to anti-OCD treatments. CONCLUSION: These
      data suggested that cyclothymic OCD could represent a specific distinct variant
      form of OCD. More vigilance is needed toward this entity which is largely under
      recognized in clinical practice.

PMID- 11995383
TI  - [A coralliform lithiasis].

PMID- 11995384
TI  - [Acinetobacter, a nosocomial pathogen. Contribution of experimental models].
AB  - EPIDEMIOLOGY: The increasing importance of Acinetobacter as a nosocomial pathogen
      responsible for outbreaks in intensive care units has been pointed out for twenty
      years. Today Acinetobacter infections are essentially pneumonia in patients under
      mechanical ventilation. EXPERIMENTAL MODELS: Most clinical isolates are resistant
      to b-lactam antibiotics as well as to other drugs. Animal models represent an
      essential step between in vivo testing an<d clinical studies, necessary to
      understand physiopathology, pharmacology and efficacy of therapy. The virulence
      of clinical isolates of Acinetobacter spp has been studied in a mouse model of
      systemic infection. Pharmacological studies and efficacy of antibiotics have been
      studied in a mouse model of Acinetobacter pneumonia. HUMAN THERAPEUTICS: The
      majority of strains are multi-resistant to antibiotics and the infections they
      cause are difficult to treat. Isolated or combined Sulbactam has often been used
      with success.

PMID- 11995385
TI  - [Bioethics and the 21st century, the physician's point of view].
AB  - In the field of human procreation, the problems raised by bioethics are multiple
      and complex. First, there is the request from couples and individuals with
      regards to the management of procreation, not only the negative requests, be it
      contraception or abortion, but also the positive requests concerning medically
      assisted procreation. Then there is the practitioner's response to the request,
      particularly for assisted procreation. The practitioner is at the heart of
      conflicting interests between the needs or desires of the patients and the
      reluctance, legitimate or not, of society, with the implication of a third
      person, embryo, fetus or newborn. And here again we are confronted with the aims
      of researchers wishing to obtain information concerning the efficacy,
      possibilities of application and potential dangers. The legists and magistrates
      are concerned with the legal status of the embryo and the fetus. However, if the
      fact of giving a legal status can solve many legal problems, it does not solve
      the problem of the eventual use of an embryo, and of its interpretation by
      philosophers and moralists. Moreover, public opinion should not be forgotten,
      including the attraction of rapid anathema, without recourse. Finally, there is
      also the role of the legislator who, here again, is confronted with several
      controversial conceptions.

PMID- 11995386
TI  - Animal welfare in relation to standards in organic farming.
AB  - The new EU-regulations on organic farming (1804/1999) are also influencing the
      animal welfare. A lot of positive regulations is to find, but also regulations
      that seen to mind more about the general public and customer and their view on
      organic farming, than the health and welfare of the animals. The paper specially
      focus on the impact of the regulations and the recommendations that
      phytotherapeutic essences and homeopathic products take precedence over the so
      called chemically-synthesised allopatic veterinary medical products, and that the
      use of the same is prohibited for preventive treatments. Key questions here are
      the lack of scientific evidence concerning homeopathy in animals, and that
      Swedish veterinarians are not allowed to work with homeopathy. Differences in
      interpretation of the regulations between animal owners and veterinarians will
      also be discussed. What is a disease that needs treatment? Who is to decide about
      the treatment? Parasitic infections are discussed as an illustrative example.
      Other consequences of the regulations concerning the animal welfare are problems
      in certain geographical zones, for instance subarctic areas where necessary crops
      are impossible to grow. Animal transports and splitting mother-offspring are
      briefly discussed as future problems to be handled in the regulations, and the
      paper ends by presenting the need of regulated herd health control programs in
      organic husbandry, which can detect and focus on welfare and production problems.
      The organic movement is not static, and must not be so.

PMID- 11995387
TI  - Animal health and welfare in organic sheep and goat farming--experiences and
      reflections from a Swedish outlook.

PMID- 11995388
TI  - Animal health and welfare--pig production.
AB  - Requirements of the organic pig farming create an opportunity to offer good life
      for animals. The space requirements give animals the possibility to exhibit
      species-specific behavior and provide them opportunity for more exercise. Bedding
      and roughage are important in helping to reduce production stress. The most
      difficult question in a veterinary point of view is how to manage the animal
      health care. Vaccinations, antibiotics and anthelmintic can be used in organic
      production but only in a limited way. A lot can be achieved with good management
      but there are still situations when the use of medicine is necessary. What is the
      amount of joint inflammations or liver spots to justify the use of medicine? The
      question has to be solved case by case. The profitability of the production is a
      crucial point in an organic farm because a poor economy is a great threat to
      animal welfare.

PMID- 11995389
TI  - Health and welfare in organic poultry production.
AB  - This review paper deals with the major health and welfare aspects of organic
      poultry production. The differences between organic and conventional egg and
      poultry meat production are discussed, with the main emphasis on housing and
      management requirements, feed composition and the use of veterinary prophylactic
      and therapeutic drugs. The effects of the legislation and statutes for organic
      farming on the health and welfare of the birds are also discussed, especially in
      relation to the biosecurity problems associated with free-range systems, the
      occurrence of behavioural disturbances in loose housed flocks and the use of
      veterinary drugs and vaccinations in general. The results from a questionnaire
      sent out to all Swedish organic egg producers, where questions about the farmer's
      perception of the birds' health status were included, are presented at the end of
      the paper. It is concluded that most of the health and welfare problems seen in
      conventional poultry systems for loose housed or free ranging birds can also been
      found on organic poultry farms. It is also concluded that there is a need for
      information about biosecurity, disease detection and disease prevention on
      organic poultry farms.

PMID- 11995390
TI  - Alternative therapy of animals--homeopathy and other alternative methods of
      therapy.
AB  - Alternative therapy of animals is described, in the meaning of alternatives to
      veterinary therapy traditionally accepted by veterinary faculties and schools and
      included in their curricula. Alternative therapy composes of different
      disciplines, of which homeopathy is emphasised in this presentation. Information
      is given on the use and interest of such therapy among veterinarians and animal
      owners. Homeopathy as other alternative therapies, may offer great advances, if
      they induce any effect. Some of the disciplines are based on a scientifically
      accepted documentation. Others, and homeopathy in particular, are missing such a
      documentation of effect. The justification of including alternative therapy in
      treating animals is discussed. Research in alternative therapy of animals is
      greatly needed, in particular to evaluate therapeutic methods which are in
      extensive use without any documented effect. An ongoing research project in
      Norway on the effect of homeopathic treatment of mastitis in cows is shortly
      presented.

PMID- 11995391
TI  - Reduced medication in organic farming with emphasis on organic dairy production.
AB  - Medication is an important focus area in organic animal husbandry. The
      combination of goals relating to improved animal welfare and reduced use of
      chemicals in general creates a common wish to reduce medication. Based on data
      from current Danish research projects in organic dairy farming, one specific
      organic medication pattern or policy cannot be described. The disease treatment
      pattern is influenced by many factors, e.g. the interaction with colleagues,
      veterinarians and agricultural advisors. No significant difference could be found
      with regard to incidence of mastitis treatments or somatic cell counts in 27
      organic and 57 conventional herds. A marked tendency to shorter treatment periods
      in relation to mastitis treatments was described for organic farms in comparison
      with conventional farms (1.9 days versus 3.2 days (5 organic and 7 conventional
      herds)). In a study of development of health advisory service in organic herds,
      the dialogue between farmer, veterinarian and agricultural cattle advisor changed
      the treatment pattern markedly during a period of 6 months. Among important
      future challenges for veterinarians in organic farming is pointed at the
      constructive, open, and critical interaction with the single organic farmer as
      well as the organic animal husbandry system in general.

PMID- 11995392
TI  - Breeding for improved disease resistance in organic farming--possibilities and
      constraints.
AB  - Lowered incidences of disease may be reached in several ways: management and
      rearing measures, vaccination programmes and preventive medications as well as
      breeding for improved disease resistance. Here the focus is on breeding for
      improved resistance to infectious diseases. In comparison to conventional
      farming, one has to acknowledge that the spectrum of diseases in animals reared
      under organic conditions is different and that the proportion of the breeding
      stock of animals in organic farming is considerably smaller. There are at least
      four different approaches that may be used in breeding towards resistance to
      infectious diseases. The most obvious is to record disease incidence in the
      progeny and select those parents that produce the progeny with the lowest
      incidences of disease. Another approach is to use breeders possessing certain
      major histocompatibility complex antigens suggested being associated with
      resistance to certain infections. A third approach is to analyse the heritability
      of a set of immune functions or related traits crucial for resistance to
      infections and then use the traits with high heritability in breeding programmes.
      Finally, one may genetically select animals for high immune response using an
      index that combines estimated breeding values for several immunological traits.
      Examples of these various approaches are given and the feasibility for using
      these in organic farming are discussed.

PMID- 11995393
TI  - Recycling biowaste--human and animal health problems.
AB  - Biowaste from the food chain is of potential benefit to use in agriculture.
      Agriculture in general and organic farming in particular needs alternative plant
      nutrients. However, the quality concerning hygiene and soil contaminants must be
      assured. This recycling has to be regulated in a way that harmful effects on
      soil, vegetation, animals and man are prevented. The problems with heavy metals
      and organic contaminants have been focused on. Still, maximum threshold values
      are continuously discussed to avoid an increase of soil concentrations. The
      effect on the ecosystems of residues from use of medicines needs further
      attention. There is also a risk for a spread of antibiotic resistant micro
      organisms in the environment and then to animals and man. Infectious diseases may
      be spread from biowaste and new routes of disease transmission between animals
      and humans can be created. Zoonotic diseases in this context play a central role.
      Pathogens recently introduced to a country may be further spread when biowaste is
      recycled. The very good health status of domestic animals in the Nordic countries
      may then quickly change. The quality of biowaste is of enormous importance if
      biowaste is to gain general acceptance for agricultural use, especially for
      organic production. A balance needs to be maintained between risk and advantage
      for its use.

PMID- 11995394
TI  - Organic farming in the Nordic countries--animal health and production.
AB  - Organic farming (or ecological agriculture) is of growing importance in the
      agricultural sector worldwide. In the Nordic countries, 1-10% of the arable land
      was in organic production in 1999. Organic farming can be seen as an approach to
      agriculture where the aim is to create integrated, humane, environmentally and
      economically sustainable agricultural production systems. Principles like
      nutrient recycling, prevention rather than treatment and the precautionary
      principle are included in aims and standards. Animal welfare is another hallmark
      of organic livestock production but despite this, several studies have indicated
      severe health problems e.g. in organic poultry production in Denmark. Also the
      quality of animal food products in relation to human health, particularly the
      risk of zoonotic infections, has been debated. For these reasons there is a need
      for improvement of production methods and animal health status. Vets play an
      important role in this development through work in clinical practice and in
      research. On-farm consultancy should be tailored to the individual farmers needs,
      and the practitioner should be willing to take up new ideas and when needed, to
      enter a critical dialogue in relation to animal welfare. Better base line data on
      animal health and food safety in organic food systems are needed.

PMID- 11995395
TI  - Zoonotic Escherichia coli.
AB  - Escherichia coli is a normal inhabitant of the gastrointestinal tract of all warm
      blooded animals, but variants of this species is also among the important
      etiological agents of enteritis and several extraintestinal diseases. The E. coli
      strains that cause diarrhoeal illness are categorised into pathogenicity groups
      based on virulence properties, mechanisms of pathogenicity, clinical symptoms and
      serology. The five main categories include enterotoxinogenic E. coli (ETEC),
      enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAggEC),
      enteroinvasive E. coli (EIEC) and Shiga (Vero) toxin-producing E. coli
      (STEC/VTEC). From a zoonotic point of view, STEC is the only E. coli
      pathogenicity group of major interest, as the shiga toxin-producing strains are
      able to cause severe disease in humans when being transmitted through the food
      chain from their animal reservoirs. The focus of this manuscript is therefore on
      STEC; pathogenicity factors, disease, the reservoirs and on-farm ecology,
      transmission into the food chain, growth and survival in food and in the
      environment, and the shiga toxin-encoding bacteriophages.

PMID- 11995396
TI  - May organically farmed animals pose a risk for Campylobacter infections in
      humans?
AB  - Organic farming of meat producing poultry like broilers, means that the animals
      should be kept outdoors as much as possible. This pose a risk that they get
      infected with Campylobacter. At slaughter, carcasses may be contaminated with
      campylobacter. If cross contamination occurs in the kitchen or if the meat is
      undercooked people may ingest the bacteria and suffer from enteritis. It seems
      possible that close to 100 percent of organically farmed flocks may be infected
      with campylobacter while under Swedish conditions only 10 percent of
      conventionally reared flocks are infected.

PMID- 11995397
TI  - U.S. Supreme Court affirms RNs belong in bargaining unit.

PMID- 11995398
TI  - Nurse-expert testifies as to standards for 'sticking' pt. Case on point:
      Mengelson v. Ingalls Health Ventures, 2001 WL 540365 N.E.2d-IL.

PMID- 11995399
TI  - GA: ER nurse on jury knew defendant doctor: court rules juror should have been
      excluded.

PMID- 11995400
TI  - TX: plaintiff's expert alleges 'staff' negligent: court holds 'staff' includes
      individual nurses.

PMID- 11995401
TI  - Nurses were illegally barred from review panel. Case on point: Harlet v. St.
      Vincent Hospitals and Health Svcs, 2001 WL 503459 N.E.2d-IN.

PMID- 11995402
TI  - [Safety and efficacy of total dose intravenous iron infusion in the treatment of
      iron-deficiency anemia in adult non-pregnant patients].
AB  - INTRODUCTION: Iron deficiency anemia (IDA) has a prevalence of 20-24.5% in
      Mexico, which is similar to other developing countries. Although the treatment of
      choice is oral iron therapy, several factors limit its efficacy. Intravenous
      administration of iron-dextran is an effective method that has been evaluated in
      pregnant women, children and renal patients and there are some studies
      demonstrating its safety in these groups. We carried out a prospective,
      longitudinal, uncontrolled clinical trial to evaluate the safety and efficacy of
      total-dose intravenous iron infusion in the treatment of IDA in adult, non
      pregnant patients. MATERIALS AND METHODS: Forty-seven patients (8 male, 39
      female) with anemia and iron deficiency were included in the study. Iron deficit
      was calculated and a total dose iron infusion was administered intravenously
      diluted in normal saline over 4 hours. CBC were obtained at 2-week intervals
      until week 8 post-infusion. The percentage of hematocrit correction was
      calculated at week 8 post-infusion. RESULTS: Baseline hemoglobin values were 78
      +/- 17.2 for the whole group, 85 +/- 20.4 for men and 78 +/- 16.7 g/L for women.
      At week 8 values were 134 +/- 10.7, 138 +/- 9.8 and 134 +/- 10.8 g/L for the
      whole group, men and women, respectively. Baseline hematocrit values were 0.27 +/
      0.05 for the whole group, 0.29 +/- 0.06 for men and 0.27 +/- 0.05 for women. At
      week 8 values were 0.42 +/- 0.03, 0.43 +/- 0.03 and 0.42 +/- 0.03 for the whole
      group, men and women, respectively. The percentage of hematocrit correction was
      51.5 +/- 28.6 at week 2 and 80.3 +/- 21.3 at week 8. Thirty-two percent of
      patients developed adverse reactions, all but one being mild. CONCLUSIONS: We
      confirmed that total-dose iron infusion is a safe and effective method to treat
      IDA that may be used in patients with intolerance to oral iron or in patients
      with failure to other iron schedules, as well as initial therapy in selected
      cases. Besides it provides a swift correction of hematocrit allowing, in some
      cases, to perform elective surgery without the need of blood transfusion.

PMID- 11995403
TI  - [Renal graft survival in patients with systemic lupus erythematosus].
AB  - BACKGROUND: End-stage renal disease is an important cause of morbidity and
      mortality in patients with systemic lupus erythematosus (SLE). In 1975, the US
      Renal Transplant Registry reported the first lupus patients, who received a renal
      transplant. This study reported 60% and 55% patient/graft survival respectively
      at a mean time of two years; these results were similar to those of non-lupus
      transplanted patients in this same post-transplant lapse time. Renal
      transplantation is a world wide accepted therapeutic option in the treatment of
      SLE patients. PATIENTS AND METHODS: In order to identify the risk factors
      associated to renal graft loss in SLE patients and to compare graft survival
      between these patients and control transplant patients, matched by age, gender,
      haplotype match, and transplant date (+/- three years), we performed a
      retrospective analysis of all SLE patients that received a renal transplant in
      our Institute. RESULTS: From 1967 to March 1997, 25 (5.5%) out of 452 renal
      transplants were performed in 22 SLE patients, mean age 29 +/- 10 years, 20 were
      female (90%). In 18 patients (85.7%) we obtained pre-transplant histological
      diagnosis: 13 (72%) type IV glomerulonephritis according to the OMS
      classification, three (17%) type VI, and two (11%) type III. Twelve patients
      (57%) were subjected to hemodialysis in the pre-transplant period and none (43%)
      to peritoneal dialysis. The time elapsed between the diagnosis of SLE and the
      start of dialysis was 50 +/- 70 months, the time on dialysis was 18 +/- 17
      months, the post-transplant renal follow-up 46.9 +/- 41.5 months, and the graft
      source: 18 (78%) from living related (three sharing 0 haplotypes, 12 sharing 1
      haplotype, and three sharing 2 haplotypes), and five (22%) from cadaver donors.
      Triple drug immunosuppresive therapy (cyclosporine, azathioprine, and prednisone)
      was employed in 17 patients and double drug therapy (azathioprine and prednisone)
      in the remaining six cases. We registered seven acute rejection episodes in five
      patients (30%), one of them lost the graft. Five patients presented a post
      transplant thrombotic event, two of these were in the graft's artery. In two
      patients post-transplant SLE activity was documented, one case in with renal
      activity in the graft and the other with extrarenal activity. Risk factors
      analyzed for graft loss: number of pre-transplant thrombosis events, time elapsed
      between diagnosis of SLE at start of dialysis (< or = 6 months), time on dialysis
      (< or = 12 months), graft source, chronic rejection, and follow-up were not
      significant; in contrast, post-transplant thrombosis was the only identified risk
      factor for graft loss. Graft survival analysis at 50 months in SLE transplanted
      patients versus control non-SLE transplanted patients did not show significant
      differences (74% vs. 83%, log rank 0.11). CONCLUSIONS: Post-transplant thrombosis
      was identified as a risk factor for graft loss. In concordance with recent
      studies, pre-transplant thrombosis, time elapsed between diagnosis of SLE at
      start of dialysis and time on dialysis were not risk factors for graft loss in
      this study. Graft survival in renal transplants recipients with SLE was not
      different from that of the general renal transplant population.

PMID- 11995404
TI  - [Nuclear medicine residents' clinical aptitude for interpreting gammagraphic
      images].
AB  - OBJECTIVE: The study deals theoretical aspects of evaluation and the importance
      of consider one as part of a research process. The diverse theoretical trends in
      the field of education are synthesized in two main tendencies: the participating
      and passive education perspectives. The influences of these two tendencies in
      selection the subjects for evaluation are also discussed in order to explore the
      gammagraphic interpretation aptitude in residents of nuclear medicine. MATERIAL
      AND METHODS: An evaluation instrument developed by us to explore aptitudes result
      of a long validation process. It consists of 90 questions was applied to the
      whole sample (19 residents in two IMSS courses) in one single session. We also
      applied other instrument of multiple choice (90 questions too) within the passive
      tendency of education (control instrument). RESULTS: Scores obtained by three
      groups of residents in nuclear medicine in the aptitudes instrument, showed
      difference in accordance with the respective time of experience: first year
      obtained the lowest scores (31.5) second year showed intermediate scores (36) 3rd
      the highest (43) (p = 0.03 between 1st and 3rd). The scores obtained by the
      control instrument, was not clear difference: the 2nd year of residents was found
      better (score of 56) than 3rd year residents (score 52.5) The aptitude instrument
      is better than the control instrument in order to explored, discriminated and
      estratificated by time of formative experience in medical courses. CONCLUSIONS:
      We believe that the aptitude instrument is capable of detecting learning
      dependent on the time of clinical experience. Some considerations on the
      advantages and scope of this instrument, as compared to other current
      instruments, which are also intended to measure clinical aptitudes, are done. The
      theoretical superiority of the clinical aptitudes instrument in relation the
      others are discussed.

PMID- 11995405
TI  - Relationship between mood improvement and sleep changes with acute nicotine
      administration in non-smoking major depressed patients.
AB  - BACKGROUND: Acute administration of nicotine patches produced rapid eye movement
      sleep (REM) increases in non-smoking major depressed patients as well as clinical
      improvement in mood. Antidepressant effect was also observed after four
      continuous days of nicotine administration. The main goal of the present study
      was to observe the relationship between changes in REM sleep variables and mood
      in non-smoking major depressed patients. METHOD: Fifteen major depressed patients
      (DSM-III-R) were studied under the following sleep laboratory conditions:
      habituation, two all-night polysomnography recordings, the first one was baseline
      and the second one was nicotine patch (17.5 mg) night. Patients should had a HAMD
      21 punctuation equal or above 18 points for to be admitted in the study. A short
      HAMD (10 items), and side effect scale was used daily during the two recording
      nights. RESULTS: A significant increase in REM sleep time and reduction in sleep
      stage II was observed when patients were on nicotine patches. Ten patients
      improved (reduction of 30% in the HAMD of 10 items), the morning after nicotine.
      All of them also increased REM sleep time above their baseline. Eight patients
      from the one with significant improvement had a short REM sleep latency below 60
      minutes at baseline. CONCLUSIONS: The hypersensitivity of the cholinergic system
      may be related to the REM sleep enhancement effect observed in some of the
      patients when received nicotine and also related to the clinical improvement. The
      role of the acetylcholine in depression could be explored with the administration
      of transdermal nicotine patches.

PMID- 11995406
TI  - Evolution of hepatitis C virus-specific T cell responses and cytokine production
      in chronic hepatitis C patients treated with high doses of interferon-alpha.
AB  - OBJECTIVE: To assess the evolution of in vitro T cell response to hepatitis C
      virus (HCV) Core, E1, E2 and NS3 antigens in 10 patients with chronic hepatitis
      C, before, during and after a high dose interferon alpha (IFN-alpha) therapy, and
      to evaluate the influence of IFN-alpha on the in vivo and in vitro production of
      tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma).
      METHODS: T cell response to HCV antigens was evaluated by lymphoproliferation
      assays. In vivo and in vitro cytokine production was evaluated at weeks 0, 4, 8,
      and 12 of IFN-alpha therapy by enzyme immunoassays. RESULTS: In general, of all
      HCV antigens tested throughout the follow-up, those belonging to the Core region
      were the most immunostiumlatory. This observation was valid in IFN-alpha
      responders as well as IFN-alpha non-responders. The lymphoproliferative response
      to HCV antigens increased during IFN-alpha therapy. Serum levels of TNF-alpha
      were significantly increased in HCV patients, and six out of ten patients showed
      increased IFN-gamma serum levels. A significant decrease of IFN-gamma levels was
      observed during therapy and the same trend was seen for TNF-alpha. Mitogen
      stimulated TNF-alpha and IFN-gamma production before therapy did not differ from
      that of normal controls, however, the cytokine production was reduced at week 4
      of therapy, corresponding with a clinical improvement. A return to pretreatment
      values was observed after 8 weeks of therapy. CONCLUSIONS: a) Core antigens are
      the most immunostimulatory HCV antigens at the T cell level in chronic hepatitis
      C patients; b) High dose IFN-alpha therapy induces an increase in
      lymphoproliferative response to HCV antigens; c) Serum levels of TNF-alpha are
      increased in HCV patients; d) High dose IFN-alpha therapy induces a decrease in
      serum levels of IFN-gamma; e) High dose IFN-alpha therapy induces a transiently
      decreased mitogen-induced TNF-alpha and IFN-gamma production.

PMID- 11995407
TI  - Delayed administration of G-CSF until day +7 after autologous peripheral blood
      stem cell transplant is as effective in accelerating hematopoietic as day 0.
AB  - PURPOSE: To compare the hematopoietic recovery and the clinical outcome after
      high dose chemotherapy and peripheral blood stem cell (PBSC) transplant between
      patients who received recombinant granulocyte colony-stimulating factor (G-CSF)
      starting on day 0 and those who received it starting on day +7. PATIENTS AND
      METHODS: Thirty-five consecutive patients received high dose chemotherapy with
      ifosfamide, etoposide and carboplatin (ICE) and autologous PBSC transplant. PBSC
      mobilization was achieved with G-CSF. In 19 transplants done in 1994, G-CSF was
      started on day 0 and in 16 procedures done in 1995, G-CSF was started on day +7.
      In both groups G-CSF was given until the absolute neutrophil count was 1 x
      10(9)/L. RESULTS: The median number of days to reach an absolute neutrophil count
      > 0.1 x 10(9)/L, was 11 in the patients who started the G-CSF on day 0 and 11
      days in the patients with delayed administration of G-CSF and to reach > 0.5 x
      10(9)/L 14 days and 13 respectively. The median number of days to reach a
      platelet count > 20 x 10(9)/L was 14 and 13. Comparison of early vs. delayed
      administration of G-CSF did not show any significant differences regarding the
      time to achieve platelet independence, number of days with fever, median days of
      hospital stay, number of red cell or platelet transfusions. CONCLUSIONS: Starting
      G-CSF on day +7 after high dose ICE chemotherapy and autologous transplant of
      PBSC is as effective in restoring the hematopoietic function as is starting its
      administration on day 0.

PMID- 11995408
TI  - [Genetic therapy of cancer].
AB  - Gene therapy is a new modality of treatment in which a gene is used to modify or
      add new biochemical properties to a patient's target cells with therapeutics
      purposes. Currently, this experimental therapy is under intensive development as
      an alternative to treat cancer, because it is possible that this therapy may
      generate a higher antineoplastic activity, more tissue selectivity and less
      contralateral effects than conventional therapy. After a decade of preclinical
      and clinical assays, still there are several obstacles that impose limits to the
      antineoplastic efficacy of this therapy. However, with the advances in molecular
      biology and related fields, there is a promise to improve, expand and strength
      the powerful antineoplastic arsenal of gene therapy.

PMID- 11995409
TI  - [Genomic medicine and the physiopathology of arterial hypertension].

PMID- 11995410
TI  - [The bioterrorism menace: a global focus for assisting physicians from spanish
      and european perspectives].

PMID- 11995411
TI  - [Importance of water-soluble vitamins as regulatory factors of genetic
      expression].
AB  - Among nutrients, the role of water-soluble vitamins as genetic expression
      modulators has not been exhaustively stu-died. Relevant information is shown
      herein on the present state of the art in this field. For example, vitamin C
      deficiency leads to a decrease in mRNA levels of apolipoprotein A1 (Apo A1) in
      liver. Biotin participates in the regulation, both at mRNA and protein level, of
      the enzymes that participate in its own metabolic cycle and of enzymes that
      contribute to glucose metabolism. Thiamine regulates the expression of some genes
      that code for enzymes using thiamine diphosphate as cofactor. Thiamine deficiency
      diminishes the mRNA levels of transketolase and pyruvate dehydrogenase. It has
      been shown in riboflavin-deficient rats that FAD regulates some acetyl CoA
      dehydrogenases, producing a marked increase in mRNA levels. Nicotinamide
      positively regulates glyceraldehyde-3-phosphate dehydrogenase when NADH is added.
      Vitamin B6 modulates the expression of a variety of genes that respond to
      hormones. Vitamin B12 increases concentrations of the enzymatic protein
      methionine synthetase and doe not affect mRNA levels, which implies that this
      protein is regulated by its cofactor post-transcriptionally. Most mechanisms
      involved in these regulation examples are not known, which opens new research
      areas for the future.

PMID- 11995412
TI  - [Epistemological focus on sphygmomanometry].
AB  - In the XVIII century, the English naturalist Stephen Hales started to apply blood
      sphygmomanometry in animals. Direct recording of the blood pressure was first
      applied, in the XIX century, by AE Chauveau and JLM Poiseuille. However, it was
      not until 1856 that it was possible to perform a direct determination of blood
      pressure in humans by means of a device designed by Faivre. The first
      sphygmomanometer appeared at the end of the XIX century. The physician Samuel K.
      von Basch, native of Prague and who lived a few years in Mexico, fabricated
      successively three models of sphygmomanometers. The first (1881), with a mercury
      column, proved to be the most practical and useful. This instrument inspired the
      sphygmomanometer of the Italian physician Scipione Riva-Rocci who presented it in
      1896. His sphygmomanometer, supported on the Vierordt principle, could measure
      manometrically the force needed to stop the pulse wave. Thanks to the research of
      Russian physician N. Korotkoff, the auscultatory method was added to
      sphygmomanometry. During the XX century other instruments to measure blood
      pressure were fabricated: the Pachon's and Plesch's oscillometers, as well as the
      aneroid manometer. On the other side, the use of direct tensional recordings has
      subsisted which has allowed to document the wide oscillations of arterial
      pressure levels during the day. Anyway, the sphygmomanometer with a mercury
      column has persisted until the present and will still be used for a long time. A
      new evolving methodology is the continuous ambulatory sphygmomanometry.

PMID- 11995413
TI  - [Why do Mexican researchers resist sending manuscripts to Mexican journals?].

PMID- 11995414
TI  - Neurosurgical suite of the future. I.
AB  - Although the past 10 years have seen a huge influx of technology into the
      operating room, the environment within which this technology is used has not been
      greatly modified. The result is a poorly integrated collection of machines and an
      overcrowded situation in the floor space around the operating room table.
      Clearly, many areas are open for improvement in the process of surgery, from
      booking a case to carrying out the operation. Newer operating room designs need
      to incorporate the flexibility to handle the ever-increasing digital information
      load that is being generated and that is necessary for the surgical environment
      to be efficient in time and cost. Room for expansion without major reconstruction
      should also be incorporated in these designs. In addition, because one operating
      room design cannot be all things to all specialties, specialized room designs for
      surgical services would be practical and necessary. The next 10 years will offer
      the opportunity to make some of these changes, and many groups are working toward
      making them a reality.

PMID- 11995415
TI  - Neurosurgical suite of the future. II.
AB  - The role of imaging in diagnosis and therapy has been accepted by physicians.
      This favorable reception of minimally invasive procedures resulted in the
      recognition of the feasibility of image-guided approaches. Although radiology has
      combined imaging with various novel therapeutic methods, the full use of advanced
      imaging technology has not yet been accomplished. The current trend is the
      evolution of integrated therapy delivery systems in which advanced imaging
      modalities are closely linked with high performance computing. Obviously, the
      operating room of the future will accommodate various instruments, tools and
      devices, which are attached to the imaging systems and controlled by image-based
      feedback.

PMID- 11995416
TI  - Neurosurgical suite of the future. III.
AB  - The neurosurgical suite of the future will continue to incorporate developing
      technologies so that lesion localization, surgical dissection, electrode
      placement, and cell/drug delivery will be optimized. In this article it was shown
      that MR technology can be placed into a neurosurgical operating room and used as
      a surgical adjunct in such a way that surgical, anesthetic, and nursing
      techniques are not [figure: see text] compromised. Essential to the success was
      the high magnetic field strength and system mobility. It is now hypothesized that
      MR technology, coupled to advances in molecular therapies, endovascular
      techniques, and transplantation, will continue to improve neurosurgical outcome
      not only for benign pathology but also malignant neoplastic and degenerative CNS
      disorders. Although these technologies are intriguing and ultimately will improve
      neurosurgical outcome, it is likely that for the foreseeable future, neurosurgery
      will continue to require sound clinical judgment and surgical dexterity.

PMID- 11995417
TI  - Intraoperative MR systems. Low-field approaches.
AB  - Numerous different concepts in low- and mid-field intervention have been
      described and applied for percutaneous intervention and intraoperative MR
      imaging, and each has demonstrated usefulness in specific applications. As the
      use of interventional methods under MR imaging expands, the imaging systems used
      for intervention will continue to evolve. More than likely, different system
      designs will be advocated for different interventional applications. The ultimate
      choice of interventional system will depend on each institution's optimal balance
      among the types of procedures to be performed, the required image quality, and
      the financial constraints.

PMID- 11995418
TI  - Intraoperative MR systems. Midfield approaches.
AB  - Intraoperative MR imaging provides an unrestricted view of intracranial
      structures and lesions that has revolutionized the way that neurosurgery is
      performed in the authors' institution. Intraoperative imaging allows the
      practitioner to update and adjust the approach to intracranial lesions
      continuously. With this system, important anatomic and vascular structures can be
      successfully avoided; boundaries of low-grade tumors can be accurately defined,
      and foci of possible higher grade within these lesions can be identified; foci of
      high-grade astrocytomas can be differentiated from radiated brain; hyperacute
      hemorrhage or infarction during and after procedures can be determined; and the
      possible communication of cystic collections with CSF can be ascertained. These
      advantages provide a level of comfort to the surgeon and a presumptive margin of
      safety to the patient that is unattainable during conventional surgical
      approaches, and given the choice, the authors' neurosurgeons would prefer to
      operate in the interventional magnet. Preliminary reports concerning the efficacy
      and usefulness of MR-guided navigational tools for the performance of
      neurosurgery are encouraging, as noted earlier, Wirtz et al have shown that the
      more extensive removal of glioblastomas afforded by intraoperative MR leads to
      significantly prolonged patient survival compared with conventional surgery.
      Further outcomes analysis must be performed, however, to determine whether these
      new techniques significantly decrease overall long-term morbidity or increase
      survival in those patients who have low-grade astrocytomas.

PMID- 11995419
TI  - Intraoperative MR systems. High-field approaches.
AB  - Since the introduction of MR-guided neurosurgery, the field has evolved
      considerably. As it has been convincingly demonstrated, MR-guided therapy seems
      to be feasible and safe at all clinical field strengths up to 1.5 T. This article
      discusses the technology of MR-guided therapy at 1.5 T, and in particular, the
      multiple approaches that have been advanced to date.

PMID- 11995420
TI  - Optimizing brain tumor resection. Low-field interventional MR imaging.
AB  - In this article, the authors describe their strategy for intraoperative MR image
      guidance of tumor resection at low-field (0.2 T) strength. It is their opinion
      that intraoperative imaging is most useful in assessing the resection of
      intrinsic, infiltrating brain tumors; boundaries of the tumor cannot be clearly
      distinguished with the surgeon's eyes, and therefore, this discussion
      predominantly applies to the surgical resection of gliomas.

PMID- 11995421
TI  - Optimizing brain tumor resection. Midfield interventional MR imaging.
AB  - The development of the intraoperative MR imager represents an important example
      of creative vision and interdisciplinary teamwork. The result is a remarkable
      tool for neurosurgical applications. MRT allows surgical manipulation under
      direct visualization of the intracranial contents through the eye of the surgeon
      and through the volumetric images of the MR imaging system. This technology can
      be applied to cranial and spinal cases, and forseeably can encompass application
      to the entire gamut of neurosurgical efforts. The author's experience has been
      that this device is easy and comfortable for the surgeon to use. Image
      acquisition, giving views in the plane of choice, lasts no more than 2 to 60
      seconds (depending on the imaging method), and does not increase the duration of
      a given procedure substantially. The author believes that the information
      received through intraoperative MR imaging scanning ultimately will contribute to
      decreasing the duration of surgery. Future possibilities include combining the
      intraoperative MR imager with other technologies, such as the endoscope, focused
      ultrasound, robotics, and the evaluation of brain function intraoperatively. The
      development of the intraoperative MR imager marks a significant advance in
      neurosurgery, an advance that will revolutionize intraoperative visualization as
      fully as the operating microscope. The combination of intraoperative
      visualization and precise surgical navigation is unparalleled, and its
      enhancement of surgical applications will be widespread. Considering the
      remarkable potential of the intraoperative MR imager for neurosurgical
      applications, optimal magnet design, image quality, and navigational methods are
      necessary to capitalize on the advantages of this revolutionary tool. The
      intraoperative MR imaging system that the author's team has developed and used
      has combined these features, and allows the performance of open surgical
      procedures without the need of patient or magnet repositioning. By using advanced
      navigational tools and computer technology, it represents an integration of
      frameless stereotactic methods with real-time interactive imaging. The midfield
      imager provides sufficient spatial and temporal resolution and image quality to
      assess anatomy and pathology adequately, to monitor a surgical procedure, and
      make image-based decisions. The intraoperative use of this unique system is not
      limited to biopsies or limited-access procedures. The entire range of
      neurosurgical procedures can be performed, if the requisite instrumentation is
      available. Much work remains to be done, however. The team did not develop this
      system only to enable the performance of current neurosurgical procedures. Forty
      years ago, the operating microscope enabled not only the performance of undreamt
      of procedures but opened the door to entire new subspecialties. The entire
      landscape of neurosurgery will change at a fundamental level as the full
      ramifications of this exciting idea come to fruition. The holy grail of image
      guided surgery is a seamless interface between the eye and hand in the purest
      sense (i.e., the mind's eye and hand). Ideally, this seamless interface
      represents effortless flow between the procedural goal compared with the present
      situation and the manipulation of the tools available to accomplish the task,
      whether they be the scalpel, drill, laser, ultrasonic aspirator, phased array
      focused ultrasound, microrobot, or high-dose irradiator. As in the realm of high
      performance military jet fighters, the physical limits of the human being
      demarcate the confining boundary of the system. Those limits are much tighter
      around the domain of tool manipulation, where the surgeon will yield, early on,
      to the enhanced performance of robotics and other technical adjuncts. The era of
      large open magnet imaging systems for surgical procedures then will come to a
      close; however, the grander era of the surgeon's integration of precision-guided,
      multimodality therapeutics will just be beginning. The future will be very
      bright, indeed.

PMID- 11995422
TI  - Optimizing brain tumor resection. High-field interventional MR imaging.
AB  - High-field strength iMRI guidance is an effective tool for brain tumor resection.
      Although its use lengthens the average time for a craniotomy, the reward is a
      more extensive tumor excision compared with conventional neurosurgery without an
      increased risk to the patient (Table 4). Although intraoperative patient transfer
      into and out of the magnet is cumbersome, the possibility for complete resection,
      especially for a low-grade glioma, makes the effort worthwhile. The cost and
      technical support required for this system presently limits its use to only a few
      sites worldwide. As with any technology, further refinements will make this
      system less expensive and more attainable. Practical consideration aside, high
      field strength iMRI is presently [table: see text] the most effective tool
      available for brain tumor resection. Because of its novelty, future studies are
      necessary to determine if this technology lowers the incidence of and extends the
      duration to tumor recurrence as the preliminary data in children suggests. These
      are the ultimate measures of efficacy for any brain tumor treatment. Based on the
      rapid advancement of technology, will today's high-field strength interventional
      magnet become tomorrow's low-field system? Very high-field strength designs may
      improve diagnostic capabilities through higher resolution, but their
      interventional applications may be hindered by increased sensitivity for
      clinically insignificant abnormalities and decreased specificity for clinically
      relevant lesions. As new technology is developed, clinicians must continue to
      explore and refine the existing high-field strength iMRI to make it cost
      effective and widely applicable.

PMID- 11995423
TI  - Neuronavigation in interventional MR imaging. Frameless stereotaxy.
AB  - The main thrust of diagnostic MR imaging is to discern normal and pathologic
      patient morphology and function. Intraprocedural imaging, however, serves a
      different goal: to furnish the surgeon or interventionalist with updates on
      intraoperative changes and how they may modify preintervention data. Although
      researchers have not established whether MR image-guided therapy can improve
      clinical outcomes and reduce complication rates definitively, the intraoperative
      and preoperative data generated will improve the ability of every neurosurgeon to
      navigate in the surgical field more accurately.

PMID- 11995424
TI  - Neuronavigation in interventional MR imaging. Prospective stereotaxy.
AB  - A practical MR imaging-based guidance/control methodology has been developed
      successfully and validated for improving the performance of stereotactic
      neurosurgerical procedures such as brain lesion biopsy. The use of the device and
      method in 40 routine MR-guided procedures has revealed its potential as an
      alternative approach. Superior to the traditional stereotactic systems, which
      rely on the old images, the new method, based on prospective guidance, can
      provide good and acceptable targeting accuracy in the presence of brain shift.
      Furthermore, the use of MR monitoring of the overall neurosurgical procedure
      provides another independent assurance for the success of a complicated surgery.
      The advantages of the new surgical guidance system and method are simple and
      compatible with the existing capabilities of conventional MR scanners. More
      importantly, it allows a more effective surgical guidance in the presence of
      brain shift during the typical neurosurgery. Another important advantage of the
      guidance method and device is the performance of a truly MR-guided neurosurgical
      procedure in a conventional, short bore high field MR scanner. Surgical
      procedures using the guidance system and method have been accepted by
      radiologists and neurosurgeons as an attractive MR-based stereotactic approach.
      It can be expected that this guidance scheme will be a useful addition to the MR
      based stereotactic system for neurosurgery, and animal research, in which
      cumbersome stereotactic frames have been used.

PMID- 11995425
TI  - Minimally invasive procedures. Interventional MR image-guided neurobiopsy.
AB  - Neurobiopsy using intraoperative MR imaging represents a natural progression from
      stereotaxis in the method with which neurosurgeons perform brain biopsy.

PMID- 11995426
TI  - Minimally invasive procedures. Interventional MR image-guided functional
      neurosurgery.
AB  - Intraoperative MR imaging techniques have the potential to greatly improve the
      stereotactic methods used for functional neurosurgery. No longer are
      neurosurgeons and patients always constrained by uncomfortable head frames and
      conventional stereotaxy. Accuracy and complication avoidance are improved by
      intraoperative imaging. Safety of operative machinery and equipment in an MR
      imaging operative suite is attainable, even with deep brain stimulating
      electrodes in depth electrodes for epilepsy. Although cost-effectiveness remains
      to be determined (see article by Kucharczyk et al in this issue), the minor
      inconveniences of operating within an iMRI environment seem to be significantly
      outweighed by the benefits.

PMID- 11995427
TI  - Minimally invasive procedures. Advances in image-guided delivery of drug and cell
      therapies into the central nervous system.
AB  - Image-guided transparenchymal delivery of drugs is an emerging neurosurgical
      modality that holds the promise of delivering various agents directly across the
      blood-brain barrier. Potential large-scale applications for convection-enhanced
      delivery of drugs through the interstitial space include the delivery of
      chemotherapeutic agents and gene therapy vectors for the treatment of brain
      tumors and the delivery of neurotrophic factors and neurotransmitters for the
      treatment of neurodegenerative disorders. The related technique of direct
      intraparenchymal injection of cells provides a means for transplanting neural
      stem cells into the brain for the treatment of degenerative diseases. Significant
      advances in catheter design, infusion strategies, and imaging technology have
      brought these procedures into the mainstream of human clinical testing, with
      clinical applications potentially on the near horizon.

PMID- 11995428
TI  - Thermal therapies in interventional MR imaging. Focused ultrasound.
AB  - MR image-guided focused ultrasound (FUS) provides an entirely noninvasive
      approach for local thermal therapies. MR imaging allows target definition and
      continuous temperature mapping. Therefore, the heating procedure can be
      controlled spatially and temporally based on automatic feedback to the FUS
      apparatus. Phased-array ultrasound technology will further help the development.
      MR imaging/FUS may be applied not only for tissue ablation, but also for local
      drug delivery, gene therapy, and drug activation.

PMID- 11995429
TI  - Thermal therapies in interventional MR imaging. Laser.
AB  - Laser ablation of cerebral tumors is an alternative to surgical excision and
      radiosurgery; however, more clinical testing is necessary. Various MR parameters
      can be used during laser ablation to detect structural as well as temperature
      changes in near real-time for diagnostic and therapeutic applications.
      Unfortunately, MR-guided ablation does not solve the problem of defining a
      precise target in high-grade tumors of the central nervous system.

PMID- 11995430
TI  - Thermal therapies in interventional MR imaging. Cryotherapy.
AB  - Cryotherapy of the brain is an old and well-established technique of functional
      and resective neurosurgery. With the use of modern imaging techniques such as MR
      imaging, which is ideally suited for diagnosis, planning, and monitoring of an
      ablation procedure, cryotherapy can become a modern alternative to other ablation
      techniques. In contrast to hyperthermal ablation tools such as laser or
      radiofrequency ablation, cryotherapy has specific potentials. First and most
      importantly, the freezing process ideally can be precisely monitored by MR
      imaging during the procedure without any specific temperature-sensitive pulse
      sequence. As shown in the experimental study, several techniques including
      conventional gradient echo sequences, ultrafast subsecond MR sequences, and MR
      fluoroscopy, are suited for monitoring the freezing process. Furthermore, the
      volume of the damaged tissue, as imaged by MR imaging, does not increase after
      completion of the ablation procedure. The extension of the ice corresponds well
      to the final, histologically confined necrosis and allows a high predictability
      of the resulting necrosis. Although not yet in clinical use, the combination of
      minimally invasive modern cryotherapy devices and ultrafast interventional MR
      techniques offer a promising alternative to other ablation techniques. In
      addition, it holds great promise for minimally invasive neurologic procedures in
      the near future. Further technical modifications and clinical studies, however,
      are necessary to establish the potential of this new treatment option.

PMID- 11995431
TI  - Cost-efficacy of MR-guided neurointerventions.
AB  - This article summarizes the available data on the cost-efficacy of interventional
      MR imaging and discusses its potential future role in the diagnosis and
      management of neurologic diseases and disorders.

PMID- 11995432
TI  - Disease managers urged to focus on epidemic of obesity.

PMID- 11995433
TI  - Roche turns to DM to boost patient compliance with its weight loss drug.
AB  - It can be tough getting patients to take their medicines as prescribed,
      particularly when there are side-effects or other barriers involved. To get
      around this problem, Roche decided to develop a DM approach to guide patients
      taking the organization's new weight-loss agent, XENICAL. In place now for 15
      months, the telephonic program is boosting compliance and getting the intended
      results.

PMID- 11995434
TI  - CA health plans collaborate in 'pay for performance' program to boost chronic
      care management.
AB  - In an unprecedented move, six of California's largest health plans have agreed to
      go along with a common scorecard that will be used to measure provider groups on
      clinical quality and patient satisfaction. Developers of the program are taking
      specific aim at chronic care management as well as preventive medicine, and
      they're hoping the effort establishes a new model for boosting care at the
      provider level.

PMID- 11995435
TI  - Boost glycemic control in type 2 diabetics with stress management training.
AB  - Why? Because studies confirm that stress can have an adverse effect on glycemic
      control. Individualized therapy has been proven effective in such cases, but now
      for the first time one study shows that a more practical, group approach to
      stress management can produce impressive results as well.

PMID- 11995436
TI  - Hospital group targets lack of awareness regarding women and CVD.
AB  - Experts aren't entirely sure why, but there is a significant gap in awareness
      regarding the risk of CVD in women as opposed to men. As a result, surveys show
      that women are not being adequately advised regarding their risk factors, and
      adverse events are not always picked up as readily. A coalition of community
      hospitals has launched a national campaign designed to bring providers and
      consumers up to speed about what they should be doing to combat CVD in women.

PMID- 11995437
TI  - CT-guided percutaneous ethanol injection therapy for ultrasonically invisible
      hepatocellular carcinoma.
AB  - We report the case of a 75-year-old woman with hepatitis C virus-related
      cirrhosis and recurrent hepatocellular carcinoma located just beneath the
      diaphragm. Computed tomography-guided percutaneous ethanol injection therapy was
      performed, because images of the tumor were hard to obtain on ultrasonography.
      The angle and depth of needle insertion were determined by using the geometric
      relationship between the target lesion and the skin insertion site on computed
      tomography scans. A 22-gauge needle was inserted through the right 6th
      intercostal space under local anesthesia. Computed tomography scanning was
      repeated to verify the needle position. After entry of the needle into the target
      lesion was confirmed, 10 mL of absolute ethanol was injected. This procedure
      caused transient mild pain, but there were no serious adverse effects such as
      pneumothorax or hemothorax. Three months after treatment, the lesion was not
      enhanced on dynamic computed tomography scanning, suggesting complete tumor
      ablation. At present, the patient is doing well. In conclusion, computed
      tomography-guided percutaneous ethanol injection therapy was safe and accurately
      achieved the desired tumoricidal effect in a patient with ultrasonically
      invisible hepatocellular carcinoma.

PMID- 11995438
TI  - Procedure of extended hilar bile duct resection and its application for hilar
      cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Several surgical procedures from hilar bile duct resection to
      hepatectomy have been adopted for hilar cholangiocarcinoma. However the details
      of the surgical procedure and the indications for hilar bile duct resection have
      not been determined. METHODOLOGY: Pathohistological outcome of resected specimens
      in five patients undergoing extended hilar bile duct resection was reviewed and
      compared with 12 patients undergoing partial hepatectomy with caudate lobectomy.
      RESULTS: Extended hilar bile duct resection was used for older patients, cases of
      choledochal site and less invasive tumor. The mean lengths of the left hepatic
      duct (21.7 +/- 7.8 mm) and the anterior hepatic duct (18.0 +/- 3.2 mm) in the
      specimens resected by extended hilar bile duct resection did not differ from
      those seen in right and left hepatectomy, respectively. Furthermore, extended
      hilar bile duct resection removed partial caudal hepatic duct. However the length
      of the posterior hepatic duct removed by extended hilar bile duct resection (14.3
      +/- 2.0 mm) was significantly less than that excised in left hepatectomy (19.3 +/
      6.6 mm) (P < 0.05). The histologic positive margin rate of the extended hilar
      bile duct resection group (40%) was the same as that of the hepatectomy group
      (50%). Papillary or nodular form tumor tended to have positive ductal margins in
      both surgical techniques. On the other hand, flat tumor tended to have high
      positive rates in both ductal and excisional margins even in hepatectomy. Two
      cases with positive surgical margin died of local recurrences, however another 3
      cases with negative surgical margin are alive without recurrences from 8 to 20
      months after surgery. CONCLUSIONS: The indication of extended hilar bile duct
      resection for hilar cholangiocarcinoma is limited to cases in which the
      infiltration is confined to the hepatic bifurcation, such as type I and type II
      of Bismuth classification with regard to papillary and nodular macroscopic
      appearance.

PMID- 11995439
TI  - Massive hemobilia.
AB  - BACKGROUND/AIMS: Massive hemobilia is a relatively rare, but potentially life
      threatening cause of upper gastrointestinal hemorrhage. We report our experiences
      in the treatment of 15 cases of massive hemobilia with different underlying
      pathologies. METHODOLOGY: Massive hemobilia is defined as a patient with blood
      discharge from the biliary tree and requiring whole blood transfusion for at
      least 4 u (1 u = 250 cc). Fifteen such patients were collected during an 8.5-year
      period (from January 1986 to July 1994), and the clinical courses of these
      patients were retrospectively reviewed. RESULTS: Among these 15 patients, 11 were
      males and 4 were females. Age distribution was from 33 to 78 years old. Mean age
      was 59.7 years. The cause of hemobilia included: percutaneous transhepatic
      biliary drainage in 7 patients, surgical trauma in 3, choledochoscopic extraction
      of biliary calculi in 1, pancreatic cancer in 1, radiotherapy for
      cholangiocarcinoma in 1, after operation for biliary lithiasis in 1, and rupture
      of the pseudoaneurysm in 1. In 11 patients, hemobilia was first noted by bleeding
      from percutaneous transhepatic biliary drainage tube (n = 10) or T-tube (n = 1).
      Three patients had hemobilia during choledocholithotomy. The other one was
      diagnosed by choledochoscopy. Treatment included pitressin infusion from
      angiographic catheter in one patient, transarterial embolization in 1, hepatic
      artery ligation in 1, hepatic artery ligation and transarterial embolization in
      1, choledochotomy or choledocholithotomy in 2, and blood transfusion only in 9.
      Two of the four mortality cases had underlying malignancy. CONCLUSIONS: The most
      common cause of massive hemobilia was percutaneous transhepatic biliary drainage
      procedures. Eight cases were successfully treated with blood transfusion only.
      Transarterial embolization, hepatic artery ligation and open drainage were
      effective non-surgical and surgical procedures, but the former two procedures
      might not be successful if sudden and severe hemobilia developed, or when an
      aberrant hepatic artery existed. Main hepatic artery had better been isolated
      before removal of the percutaneous transhepatic biliary drainage tube during
      operation.

PMID- 11995440
TI  - Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection:
      univariate and multivariate analysis.
AB  - BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma is clinicopathologically
      distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the
      prognostic factors after hepatic resection of these rare tumors are not well
      documented. The aim of this study was to evaluate prognostic factors of
      intrahepatic cholangiocarcinoma after hepatic resection. METHODOLOGY: We
      retrospectively studied 20 consecutive patients with intrahepatic
      cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to
      1998. Fifteen prognostic factors were evaluated for their association with
      overall and disease-free survivals in univariate and multivariate analysis (Cox's
      proportional hazards model). RESULTS: Eighty percent of the resected patients had
      major hepatectomy. Operative morbidity and mortality rates were 30% and 0%,
      respectively. Four patients (20%) survived more than 5 years without recurrence
      after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free
      survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and
      43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal
      invasion tumor or the presence of vascular invasion, lymphatic invasion, and
      lymph node metastasis as significant poor prognostic predictors contributing
      overall and disease-free survivals. Multivariate analysis revealed only lymph
      node metastasis as an independent prognostic factor affecting disease-free
      survival. During the same time, 17 unresectable patients were treated by
      intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or
      radiation (1). Median overall survival time in resected patients (16 months) was
      significantly better than in unresectable patients (5 months) (P = 0.005).
      CONCLUSIONS: Hepatic resection remains to be the best current therapeutic option.
      The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was
      determined by lymph node metastasis. New adjuvant chemotherapy after surgery is
      imperative for such patients.

PMID- 11995441
TI  - Three cases of primary sclerosing cholangitis associated with ulcerative colitis;
      diagnostic usefulness of magnetic resonance cholangiopancreatography.
AB  - BACKGROUND/AIMS: Primary sclerosing cholangitis is often accompanied by
      inflammatory bowel disease in western countries. However, the incidence of
      primary sclerosing cholangitis in patients with ulcerative colitis appears to be
      much lower in Japan. METHODOLOGY: Between 1980 and 1998, a total of 402 patients
      with ulcerative colitis were seen in our department. The patients were evaluated
      by abdominal ultrasonography, endoscopic retrograde cholangiopancreatography,
      and/or magnetic resonance cholangiopancreatography when persisting abnormalities
      of biochemical findings suggested the presence of hepatobiliary diseases.
      RESULTS: Of the 402 patients with ulcerative colitis, 3 patients with primary
      sclerosing cholangitis were found. There were 2 men and 1 woman. One patient had
      left-sided colitis while 2 had total colitis. Magnetic resonance
      cholangiopancreatography was done in 2 of these 3 patients and demonstrated
      diagnostic features of primary sclerosing cholangitis. All 3 patients had intra-
      and extrahepatic involvement by primary sclerosing cholangitis. One male patient
      died due to progressive hepatic failure. The other male patient was treated with
      ursodeoxycholic acid, but serum alkaline phosphatase level remained above the
      normal range. The female patient maintained normal serum alkaline phosphatase
      levels without specific medication. CONCLUSIONS: Magnetic resonance
      cholangiopancreatography is the most safe and convincing tool for the diagnosis
      of coexistent primary sclerosing cholangitis in the patients with ulcerative
      colitis.

PMID- 11995442
TI  - Relationship between types of common channel and development of biliary tract
      cancer in pancreaticobiliary maljunction.
AB  - BACKGROUND/AIMS: The incidence of biliary tract cancer development is high among
      patients with pancreaticobiliary maljunction. However, there have been no reports
      published evaluating the incidence of development of biliary tract cancers in
      pancreaticobiliary maljunction based on the morphology of the common channel at
      the junction of the bile and pancreatic ducts. We evaluated between types of
      common channel and development of biliary tract cancers in pancreaticobiliary
      maljunction. METHODOLOGY: During the last 21 years, we have experienced 78
      patients with pancreaticobiliary maljunction. Of those patients, 44 adult
      patients, whose morphologic types of common channel were identified by
      cholangiography, were enrolled in this study. The dilatation patterns of the
      common channel were classified into 3 types: A type (moderately dilated type), B
      type (markedly dilated type), and C type (non-dilated type). Evaluated items
      included the length and dilation patterns of the common channel, incidence of
      development of biliary tract cancers and proliferative activity in the biliary
      tract epithelium. RESULTS: Seventeen patients had a common channel shorter than
      20 mm, while 27 had a common channel of 20 mm or longer. Eleven patients with a
      common channel of 20 mm or longer had development of bile tract cancers. The
      dilation patterns of the common channel were classified as A (11 patients), B (16
      patients) and C type (17 patients). Amylase levels in the biliary tract were
      higher in patients with A and B type than in patients with the C type.
      Development of gallbladder cancer was observed in 6 patients with A, 2 patients
      with B and one patient with C, while development of bile duct cancer was observed
      in 2 patients with C and one patient with B. The PCNAL.I. of the biliary
      epithelium was higher in patients with A, B and C type in descending order.
      CONCLUSIONS: The incidence of development of biliary tract cancer was higher in
      patients with common channel of 20 mm or longer. The proliferative activity in
      the biliary epithelium was accelerated in patients with A type, together with a
      high incidence of development of gallbladder cancer.

PMID- 11995443
TI  - Macroscopic types of intrahepatic cholangiocarcinoma: clinicopathologic features
      and surgical outcomes.
AB  - BACKGROUND/AIMS: The prognosis of patients with intrahepatic cholangiocarcinoma
      is different for the different macroscopic types of this tumor. This study
      correlated clinicopathologic features and outcome after surgery with macroscopic
      types of intrahepatic cholangiocarcinoma to determine prognostic predictors.
      METHODOLOGY: Resected intrahepatic cholangiocarcinomas were classified into the
      following growth types: mass-forming (n = 10), periductal-infiltrating (n = 11),
      mass-forming plus periductal-infiltrating (n = 14), and intraductal (n = 2).
      Intraductal tumors were not considered further. The prognostic significance of
      clinicopathologic features was determined by univariate and multivariate
      analyses. RESULTS: Perineural invasion (P = 0.00051), lymphatic invasion (P =
      0.0088), and positive resection margin (P = 0.028) were less frequent in patients
      with mass-forming tumors than with mass-forming plus periductal-infiltrating
      tumors. Patients with mass-forming plus periductal-infiltrating tumors had
      shorter survival than those with mass-forming tumors (P = 0.0072). By univariate
      analysis, an elevated serum carcinoembryonic antigen concentration, lymphatic
      invasion, lymph node metastasis, intrahepatic metastasis, and positive resection
      margin predicted shorter survival after surgery. An elevated serum
      carcinoembryonic antigen concentration, lymphatic invasion, and positive
      resection margin were independent prognostic factors on multivariate analysis.
      The macroscopic type did not correlate independently with prognosis. CONCLUSIONS:
      Extended hepatic resection should be performed in patients with intrahepatic
      cholangiocarcinoma to obtain a tumor-free margin of resection.

PMID- 11995444
TI  - The effect of biliary decompression on antibiotic biliary excretion.
AB  - BACKGROUND/AIMS: Raised biliary pressure may affect antibiotic biliary excretion.
      We evaluated whether biliary decompression for patients with biliary obstruction
      could improve antibiotic biliary excretion. METHODOLOGY: Eight patients with
      common bile duct obstruction undergoing endoscopic nasobiliary drainage were
      evaluated. During endoscopic cannulation, biliary pressure above the obstruction
      and antibiotic concentrations in the bile and peripheral blood were determined 60
      min after the intravenous antibiotic (panipenem) administration. RESULTS: Biliary
      pressure was initially elevated above normal in all the patients, but normalized
      after biliary drainage for 5 to 7 days. At the initial endoscopic retrograde
      cholangiopancreatography, the aspirated bile contained low or undetectable levels
      of the antibiotic, but the mean bile panipenem concentration and the mean
      bile/plasma ratio of panipenem concentrations significantly improved after
      biliary decompression. CONCLUSIONS: The results suggest an important role of
      biliary pressure in determining antibiotic transfer into the bile.

PMID- 11995445
TI  - Preliminary experiences of intralesional immunotherapy in cutaneous metastatic
      melanoma.
AB  - BACKGROUND/AIMS: Antigen presenting cells are inactive within tumor tissue
      because of local immunosuppression. Tumor infiltrating lymphocyte signal
      activation transducing mechanisms are also seriously impaired. Administration of
      granulocyte macrophage-colony stimulating factor may lead to antigen-presenting
      cell recovery and interleukin-2 may restore local tumor infiltrating lymphocyte
      activation. Moreover, interleukin-2 increases the systemic lymphocyte population,
      an event which seems to correlate with a better prognosis. The present phase I-II
      study was carried out to examine whether intralesional injection of granulocyte
      macrophage-colony stimulating factor followed by subcutaneous interleukin-2 would
      induce a clinical response in advanced, pretreated and elderly melanoma patients.
      METHODOLOGY: Fourteen patients over 60 years of age received intralesional
      granulocyte macrophage-colony stimulating factor (150 micrograms per lesion on
      day 1), generally divided between the two largest cutaneous lesions, followed by
      perilesional subcutaneous interleukin-2 (3.000.000/IU) for 5 days (3 to 7) every
      3 weeks. All patients received 6 courses of treatment unless progression
      occurred. Clinical evaluation of the treated cutaneous lesions was assessed at
      the baseline and before every cycle. Distant lesions were checked every two
      cycles. RESULTS: Four clinical responses (2 partial responses and 2 minimal
      responses) (28.5%), which also involved lesions that had not been directly
      treated, and seven cases of stable disease were observed. The response duration
      for partial response and minimal response was 9, 4, 4 and 2.5+ months,
      respectively. Stable disease (50%) recorded in the 7 patients was short term, 3-6
      months. Three patients rapidly progressed after 2, 2, and 1 therapy cycles,
      respectively. The patient who reached the best partial response had a fairly high
      absolute lymphocyte count (1600 to 2400/mm3). The second one, who reached a
      complete remission after subsequent locoregional chemotherapy and hyperthermia,
      had a low absolute lymphocyte count which had doubled, however, by the end of
      treatment. Blood lymphocyte values in the other patients were too varied to allow
      any correlation with clinical response. Therapy was well tolerated and only mild
      fever was observed, with the exception of one patient who had grade 3 fever, with
      muscle pain and arthralgia. CONCLUSIONS: Considering the very low toxicity
      observed, this treatment might be indicated in elderly patients for whom systemic
      therapy is no longer a viable option. Improved scheduling and timing could result
      from further studies.

PMID- 11995446
TI  - Fatty change in human hepatocellular carcinoma cell lines derived from patients
      with antibodies to hepatitis C virus.
AB  - BACKGROUND/AIMS: Evidence suggesting a relationship between fatty change in
      normal or malignant hepatocytes and hepatitis C virus has gradually accumulated,
      but less is known about the relationship between cell proliferation and fatty
      change in human hepatocellular carcinoma. METHODOLOGY: We studied the latter
      issue in two human hepatocellular carcinoma cell lines (OCUH-16 and Nuk-1)
      derived from hepatitis C virus-associated tumors. We examined the relationship
      between degree of fatty change assessed by oil-red-O staining and electron
      microscopy, actively proliferating cells counted using a monoclonal antibody to
      MIB-1 protein, and apoptotic cells counted using DNA nick-end labeling in the
      above two hepatocellular carcinoma cell lines with time lapse. RESULTS: On day 1
      in culture, fatty change was present randomly in cytoplasm of some Nuk-1 cells,
      but was not found in OCUH-16 cells. Over time, fat droplets were found more
      frequently in large hepatocellular carcinoma cells in both Nuk-1 and OCUH-16
      lines. Most of these cells were located in the periphery of hepatocellular
      carcinoma cell nests or islands as opposed to the small hepatocellular carcinoma
      cells located in the centers of nests in both lines. According to MIB-1 staining,
      these small cells proliferate more actively than the large, peripherally located
      hepatocellular carcinoma cells. Only a few apoptotic hepatocellular carcinoma
      cells were detected during culture. CONCLUSIONS: Fatty change in large
      hepatocellular carcinoma cells seems to be associated with less proliferative
      activity than was seen in small hepatocellular carcinoma cells without fatty
      change, located in more centrally cell nests, in these hepatocellular carcinoma
      cell lines.

PMID- 11995447
TI  - Colopathy associated with the systemic use of nonsteroidal antiinflammatory
      medications. An underestimated entity.
AB  - BACKGROUND/AIMS: Adverse effects of NSAIDs (nonsteroidal antiinflammatory drugs)
      on the upper gastrointestinal tract and small intestine are well described.
      Evidence is also accumulating that implicate NSAIDs in inducing and exacerbating
      damage in the distal gastrointestinal tract. In this article we describe eight
      cases of colonic inflammation associated with nonsteroidal antiinflammatory drug
      administration; our aim is to stress the importance of an underestimated entity
      by clinicians. METHODOLOGY: Over a five-year period at two clinics, eight cases
      of NSAID-colopathy have been diagnosed. Crohn's disease, ulcerative and
      infections colitis have been excluded from this analysis. In all these subjects a
      careful drug history has been taken in a prospective manner and colonic
      inflammation appeared to be directly related to NSAID administration. There was a
      time interval (mean: 20 months) between initiation of treatment with NSAID and
      presentation with diarrhea, rectal hemorrhage and tenesmus. RESULTS: A correct
      diagnosis of colopathy associated with NSAIDs administration was made on careful
      drug history, pathological findings, stool cultures and biochemical changes which
      were insignificant, in contrast to the protracted troublesome symptoms.
      Resolution of symptoms was observed on discontinuation of NSAID medication.
      CONCLUSIONS: Our report is further evidence that NSAIDs administration is
      associated with significant mucosal injury in the distal gastrointestinal tract,
      despite is underestimated by most physicians.

PMID- 11995448
TI  - Ultrasound and biochemical evaluation of liver regeneration process after
      resections for primary and metastatic tumors.
AB  - BACKGROUND/AIMS: The liver regeneration process after resective procedures is an
      important clinical problem especially in view of the growing population of
      patients requiring liver transplantations or undergoing resective procedures as
      well as those with toxic or viral liver injures. The aim of the study was to
      analyze liver regeneration potential using ultrasound examination, and liver
      function biochemical tests in the patients after liver resections. METHODOLOGY:
      Twenty-one patients with primary or metastatic liver cancer were included in the
      study (17 males, 4 females, mean age: 59.8, SD 10.3). The patients were
      undergoing gastrointestinal tract primary tumor resections with extended
      lymphadenectomy and liver metastatic tumor excisions. Liver volume was measured
      postoperatively in the follow-up ultrasound examinations and biochemical tests
      were performed before and after the procedure. Liver function and activity of p
      450 cytochrome was tested with IRIS 13C stable isotope breath analyzer. RESULTS:
      The mean time of follow-up was 12.6 months (SD 7.8) during which volume of liver
      increased on average in the first five months to 105.7, 112.1, 125.7, 131.2, and
      138.4% of the immediate postoperative value. Biochemical parameters returned to
      normal after 2-3 weeks. Four patients in whom liver failed to regenerate died due
      to cancer spread in the mean time of 6.5 months. CONCLUSIONS: Liver has
      tremendous regeneration potential. In spite of this fact, extended hepatectomies
      affect largely the functional status of residual parenchyma which may lead to a
      fatal outcome.

PMID- 11995449
TI  - Clinicohistological features of liver failure after excessive hepatectomy.
AB  - BACKGROUND/AIMS: Patients at high risk of liver failure sometimes suffer such
      failure with hyperbilirubinemia after hepatectomy. This report clarifies the
      clinicohistological findings in liver failure cases after excessive hepatectomy,
      and discusses the mechanisms of liver failure. METHODOLOGY: Of 16 patients who
      suffered liver failure after hepatectomy between May 1992 and December 1999, 7
      patients who underwent liver biopsy or autopsy were studied. The biopsy findings
      showed that, in each case, the percentages of hepatocytes that were apoptotic or
      binucleated were calculated. The number of bile plugs per 1000 micron 2 was
      counted and the thickness of collagen fibers in Disse's space was measured at 10
      sites. The total bilirubin level was monitored over time, and the triggers, other
      than excessive hepatectomy, of increases in the bilirubin level were
      investigated. RESULTS: From the histological findings, liver failure cases were
      classified into cholestatic and nonregenerative types. Regeneration of
      hepatocytes and fibrosis in Disse's space were characteristic of the cholestatic
      type, while apoptosis of hepatocytes was characteristic of the nonregenerative
      type. Other than excessive hepatectomy, postoperative infection was the only
      trigger of liver failure in the cholestatic type, and ischemic changes of the
      liver resulted in liver failure in the nonregenerative type. The total bilirubin
      level changed more slowly in the cholestatic type than in the nonregenerative
      type after postoperative complications occurred. CONCLUSIONS: Liver failure after
      excessive hepatectomy is of two types: cholestatic, mainly induced by
      postoperative infection, and nonregenerative, mainly induced by severe ischemia
      reperfusion injury.

PMID- 11995450
TI  - Treatment of malignant colonic obstructions with metal stents and laser.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and safety of
      combined endoscopic therapy with self-expanding metallic endoprostheses and laser
      application in the management of malignant colonic obstruction. METHODOLOGY:
      Between March 1998 and September 2000, obstruction of the distal colon was
      diagnosed in a total of 11 patients (6 M, 5 F, age range: 67-87 years, mean: 73).
      The site of obstruction was located in the rectosigmoid colon (n = 6), in the
      sigmoid colon (n = 4) and in the descending colon (n = 1). The etiology of
      stenosis was colorectal adenocarcinoma (n = 8), ovarian cancer (n = 2) and
      infiltrating bladder carcinoma (n = 1). In all patients the tumor was considered
      non-resectable. Six patients had confirmed metastases, one refused colostomy and
      4 were unable to undergo surgery. After radiological visualization of the
      proximal extent of the stricture, the stenosis was dilated with Savary-like (10
      patients) and pneumatic balloon dilators (1 patient-descending colon). RESULTS:
      Stents were placed successfully in 10 patients. Prostheses migration distal to
      lesion, into the sigmoid colon, was observed in one patient (bladder cancer). A
      mild autoresolved bleeding was observed in 8 patients. Five patients remained
      free of clinical colonic obstruction until their death, which occurred 6-16 weeks
      (mean: 10) after stent placement. A moderate non-occlusive ingrowth of tumor into
      the stent lumen was documented in the other 5 cases. These patients were treated
      with introspective application of Diomed laser in a total of 16 sessions (4120
      12,476 Joules each session, mean: 6258, power 10-14 W, interval between 2
      sessions 6 weeks) and died of progressive disease without clinical signs and
      endoscopic findings of reobstruction 22-56 weeks (mean: 32) after stent
      placement. CONCLUSIONS: Metallic stent placement is an adequate palliative and
      cost-effective option, effective and save, in advanced colonic obstruction due to
      non-resectable tumors. It circumvents the need for colostomy and allows the
      patient a better quality of life. Delayed stent occlusion with tumor ingrowth
      requires a regular follow-up and can be treated with introspective laser
      ablation.

PMID- 11995451
TI  - Gastric metastasis from lung carcinoma. Case report.
AB  - We report here gastric metastasis from lung carcinoma in an 80-year-old man. His
      chief complaint was epigastric pain from metastases in the stomach. Although
      metastasis from primary carcinoma of the lung to the small intestine is more
      common than has been previously suspected, symptoms are rare. Such a metastasis
      may present as bowel perforation. To find cases of lung carcinoma metastasis to
      the gastrointestinal tract is clinically rare, and there have been few reports in
      the English literature. This report describes the gastrointestinal metastasis
      from lung carcinoma.

PMID- 11995452
TI  - Low malignant epithelioid peritoneal mesothelioma: successful treatment with
      surgical therapy alone.
AB  - A 31-year-old man presented with malignant peritoneal mesothelioma. His past
      medical history was uneventful, specifically there was no personal or
      environmental asbestos exposure. The patient was treated by complete tumor
      resection including peritonectomy. Because of the histologic diagnosis of a low
      malignant, unusual highly differentiated epithelioid tumor with very low
      proliferative activity a postoperative chemotherapy was not administered. After a
      follow-up of 20 months, the patient is in excellent clinical condition and there
      is no evidence of disease by computed tomography. The present paper reports a
      case of this rare variant of malignant peritoneal mesothelioma.

PMID- 11995453
TI  - Endoscopic comparison of two cases: distal resection of reconstructed gastric
      tube.
AB  - Recently, with the improvement of the prognosis of esophageal cancer, subsequent
      gastric cancer has increased. However, the standard surgical treatment for such
      patients has not been established as of yet. Since the patient's physical
      condition is relatively poor after Ivor-Lewis esophagectomy, it is important that
      surgical strategies must be decided according to both physical and cancerous
      conditions. Hence, various surgical procedures have been reported to date. The
      authors experienced two cases with cancer occurring in the reconstructed gastric
      tube after Ivor-Lewis esophagectomy. One was subsequent primary gastric cancer,
      and the other was metastatic gastric cancer. Distal resection of the gastric tube
      including the dissection of the right gastroepiploic vessels was carried out in
      both cases. Vascular reconstruction by utilizing microsurgery technique was
      attempted for each case, but failed in one case. After surgery, four sessions of
      endoscopic examinations were carried out. In the early period, we could identify
      mucosal ischemic change in the remnant gastric tube in the case without
      successful vascular reconstruction. On the contrary, no ischemic change was
      revealed in the other with successful vascular reconstruction. Hence, we came to
      the conclusion that vascular reconstruction must be added to the cases, which
      undergo distal resection of the reconstructed gastric tube with regional vascular
      dissection.

PMID- 11995454
TI  - A case of amebic liver abscess complicated by hemobilia due to rupture of hepatic
      artery aneurysm.
AB  - We report the case of a 51-year-old man with hepatic amebic abscess complicated
      by hepatic artery aneurysm. The patient first presented with peritonitis caused
      by perforating appendicitis. Surgical treatment resolved peritonitis but
      Entamoeba histolytica was detected in the colonic mucosa. Subsequently, liver
      abscess developed and the size of the abscess increased gradually after surgery
      in spite of continued treatment with metronidazole. Brown pus was drained from
      the abscess but 13 days after the drainage process the patient complained of
      right upper abdominal pain and the drained fluid became blood-colored and stool
      became tarry in color. Enhanced computed tomography showed a hepatic artery
      aneurysm that had ruptured into the liver abscess and duodenoscopy revealed
      bleeding from the ampulla of Vater. Transcatheter arterial embolization with
      several steel coils was successfully performed which resulted in cessation of
      bleeding from the ampulla of Vater. The patient was discharged without any
      complications five weeks after rupture of the aneurysm. Our case demonstrates
      rupture of the hepatic artery aneurysm as a rare complication of amebic liver
      abscess and the effectiveness of interventional embolotherapy in this condition.

PMID- 11995455
TI  - Effectiveness of preoperative chemotherapy for far advanced gastric cancer.
AB  - We herein report a case in which preoperative chemotherapy with cisplatin and 5
      fluorouracil was found to effectively treat far advanced gastric cancer invading
      the pancreas forming a huge mass with regional and distant lymph node metastases.
      As a result of this treatment regimen, a potentially curative resection was
      performed which led to a substantially increased survival. The patient was
      treated with 10 mg of cisplatin and 1000 mg of 5-fluouracil each day
      preoperatively. After the continuous administration of these drugs for 28 days,
      the findings of extensive pancreas invasion and lymph node metastases
      dramatically disappeared. The tumor could be curatively resected by a total
      gastrectomy with lymph nodes dissection, combined with a distal pancreatectomy
      and splenectomy. A histological study of a resected specimen showed some cancer
      cell infiltration remaining within the muscularis propria with fibrous change.
      There was no evidence of either pancreas invasion or lymph node metastasis. As a
      result, postoperative adjuvant chemotherapy was performed, 14 months later lymph
      nodes recurrence was detected and the patient died 20 months after surgery. Our
      findings suggest that preoperative chemotherapy may thus be effective for the
      treatment of gastric cancer by both reducing the tumor burden and prolonging
      survival.

PMID- 11995456
TI  - Primary hydatid cyst of the pancreas related to main pancreatic duct. A case
      report.
AB  - A case of primary hydatid cyst of the pancreas related to the main pancreatic
      duct is presented. Abdominal ultrasound and computed tomography revealed a cyst
      at the tail of the pancreas. Endoscopic retrograde cholangiopancreatography
      showed dilatation of the distal part of the pancreatic duct related to the cystic
      cavity. While the diagnosis of the pancreatic pseudocyst was established
      preoperatively, the hydatid cyst was demonstrated at laparotomy and then the
      final decision of cystogastrostomy was employed. Following the uneventful
      postoperative period, the patient was discharged on the 8th postoperative day.

PMID- 11995457
TI  - Effects of IL-2 preoperative immunotherapy on surgery-induced changes in
      angiogenic regulation and its prevention of VEGF increase and IL-12 decline.
AB  - BACKGROUND/AIMS: IL-2 preoperative immunotherapy has been proven to abrogate
      surgery-induced immunosuppression in cancer patients. In contrast, at present
      there are no data about the possible influence of IL-2 on angiogenesis-related
      molecular changes determined by the surgical operation. At present, it is known
      that VEGF (vascular endothelial growth factor) is the main endogenous angiogenic
      factor, whereas the antitumor cytokine IL-12 has appeared to play an anti
      angiogenetic role. On this basis, a study was planned to evaluate the influence
      of IL-2 presurgical immunotherapy on the perioperative changes in VEGF and IL-12
      secretions. METHODOLOGY: The study was performed on 30 colorectal cancer patients
      undergoing radical surgery, who were randomly chosen to be treated with or
      without preoperative immunotherapy of IL-2 (12 million IU/day subcutaneously for
      3 consecutive days prior to surgery). Serum levels of VEGF and IL-12 were
      measured by ELISA for blood samples collected before surgery, and at days 3, 7
      and 10 of the postoperative period. RESULTS: VEGF mean concentrations
      progressively and significantly increased during the postoperative period in
      patients treated with surgery alone. Mean values of VEGF were enhanced also in
      patients pretreated with IL-2, but VEGF increase observed in the IL-2 group was
      delayed, more transient and significantly lower with respect to that found in
      controls. IL-12 mean concentrations significantly decreased during the
      postoperative period only in the control patients, whereas in the IL-2-treated
      patients IL-12 postoperative mean values were not significantly lower than those
      found before surgery. CONCLUSIONS: This preliminary study would suggest that IL-2
      preoperative immunotherapy may abrogate surgery decline in IL-12 levels and
      reduce, although not completely prevent, VEGF increase during the postoperative
      period in surgically treated cancer patients. These results would suggest that IL
      2 presurgical immunotherapy may counteract surgery-induced stimulation of the
      angiogenesis, by either opposing the decline in blood levels of the anti
      angiogenetic cytokine IL-12, or reducing the increase in those of the angiogenic
      factor VEGF.

PMID- 11995458
TI  - Tumor marker CEA in monitoring of response to tegafur-uracil and folinic acid in
      patients with metastatic colorectal cancer.
AB  - BACKGROUND/AIMS: The assessment of response to chemotherapy of solid tumors is
      generally made by measurement of tumors visualized by imaging, commonly computed
      tomography scanning. However, response assessment based on imaging is not always
      feasible because patients often have disease not measurable by imaging study,
      such as diffuse peritoneal dissemination. Furthermore, response assessment by
      imaging is expensive and time consuming. This study was carried out in an effort
      to evaluate the correlation between serial change on imaging and on CEA
      (carcinoembryonic antigen) levels for assessing chemotherapeutic response of
      patients with metastatic colorectal cancer. METHODOLOGY: Between May 1998 and
      August 1999, a total of 40 patients with metastatic colorectal carcinoma were
      enrolled in this study. All the patients had to have measurable lesions. Oral
      tegafur-uracil 300 mg/m2/day and folinic acid 60 mg/day were administered
      concurrently for four weeks, repeated every five weeks, as the first-line
      treatment. Tumor marker CEA was examined before and during the whole course of
      treatment. Response based on CEA assessment was defined as a more-than 50% drop
      in serum CEA level for more than four weeks. The correlation between serial
      change on CEA and on imaging for assessing chemotherapeutic response was
      evaluated. RESULTS: Forty patients received a total of 318 courses of treatment
      and a response rate of 32.5% (95% confidence interval, 18.0% to 47.0%), including
      five complete responses and eight partial responses, was achieved by imaging
      studies. The pretreatment CEA levels were elevated beyond the normal cut-off
      value in 34 (85%) patients. The response rate evaluated by CEA assessment was
      42.5% (17/40). Nine responders (22.5%) based on CEA had no remission on imaging.
      Agreement in assessment by imaging study and by CEA was observed in 20 patients
      (50%), including eight responders, five stable diseases, and seven progressive
      diseases. The sensitivity of falling CEA levels in the prediction of true
      responders on imaging was 62%. The sensitivity of elevated CEA levels for the
      prediction of progressive disease was 70%. Concerning the diagnostic accuracy,
      change in CEA levels in the prediction of true responders and progressive disease
      on imaging were 65% and 85%, respectively. On a follow-up of 24 months, patients
      with remarkable falling CEA levels survived significantly longer than non
      responders (P = 0.0184, log-rank test). CONCLUSIONS: The measurement of CEA
      levels might be useful in monitoring chemotherapeutic response and in predicting
      the prognosis of patients with metastatic colorectal cancer. Serum CEA level may
      be used as a means of monitoring chemotherapeutic response when imaging study is
      unsuitable for assessing the response in clinical practice.

PMID- 11995459
TI  - Therapeutic strategy of emergency surgery for colon cancer in 71 patients over 70
      years of age in Japan.
AB  - BACKGROUND/AIMS: The prognosis for colon cancer is poorest in cases of emergency
      situation in the elderly not only in Japan, but worldwide. The aim was to design
      a therapeutic approach used for colon cancer in the elderly. METHODOLOGY: Seventy
      one patients, who were all older than 70 years, with colon carcinoma in an
      emergency situation were examined. Lethality, surgical procedure, risk of
      comorbidity, multiple organ system failure and the effect of endotoxin absorption
      were examined. RESULTS: Any increase in comorbidity was associated with a higher
      clinical lethality in the lungs, heart, kidney, and diabetes. The highest
      postoperative mortality rate was recorded in patients who underwent primary
      resection after perforation, while the lowest postoperative mortality rate was
      recorded in patients who underwent primary resection after obstruction.
      Postoperative failure of the lungs and heart and renal failure were associated
      with a significantly higher mortality rate. Twenty-five septic patients received
      an endotoxin adsorption due to blood filtration and 8 patients survived. Of the
      eight survivors, the endotoxin concentration was significantly decreased by an
      endotoxin absorption. CONCLUSIONS: In cases of ileus, the resection may be
      performed positively. In cases of perforation, we may safely say now that stoma
      and resection is to be recommended. Endotoxin absorption due to blood filtration
      may be an effective additional therapy for post-operative septic shock.

PMID- 11995460
TI  - Is postoperative radiotherapy useful for the rectal carcinoma in the era of total
      mesorectal excision?
AB  - BACKGROUND/AIMS: The exact role of postoperative radiotherapy following curative
      surgery of rectal carcinoma has been debated. In this retrospective study, we
      examined the effect of radiotherapy on the survival and recurrence rate of rectal
      cancer patients who underwent total mesorectal excision. METHODOLOGY: Since June
      1994, stage II and III rectal cancer patients have been recommended to receive
      postoperative chemoradiation. Among 175 consecutive patients who had undergone
      total mesorectal excision, 120 completed postoperative chemoradiation (group A)
      and 55 patients declined to receive radiation therapy (group B). For the two
      groups, survival and recurrence rates were compared. Mean follow-up time was 24.7
      months. There was no difference between two groups with regard to sex, mean age,
      stage of the disease, mean tumor height, type of operation and mean follow-up
      duration. RESULTS: Overall recurrence rate showed no difference between the two
      groups (24.0% vs. 25.0%, P = 0.28). Local recurrence rate was also similar (10.0%
      vs. 6.0%, P = 0.11). There was no significant difference in duration to initial
      recurrence (14.0 months vs. 11.0 months, P = 0.18). The 5-year disease-free
      survival was 57% in group A and 63% in group B (P = 0.33). Disease-free survival
      in stage II was significantly better than in stage III. (78% vs. 42% overall, 70%
      vs. 37% in group A, 92% vs. 44% for group B, P < 0.01). CONCLUSIONS: In this
      study, we found no beneficial effect of postoperative radiation therapy following
      total mesorectal excision for the rectal cancer. So far, the prognosis was
      critically dependent on the stage rather than presence or absence of radiotherapy
      after total mesorectal excision.

PMID- 11995461
TI  - Elevated serum PIIINP and laminin in inflammatory bowel disease indicate
      hepatobiliary and pancreatic dysfunction.
AB  - BACKGROUND/AIMS: Levels of S-PIIINP (serum aminoterminal propeptide of type III
      procollagen) have been shown to be increased in patients with primary sclerosing
      cholangitis and inflammatory bowel disease. The aim of the study was to
      investigate the serum concentrations of PIIINP and laminin in inflammatory bowel
      disease patients, their relationship with inflammatory bowel disease-associated
      hepatobiliary and pancreatic dysfunction, and to correlate them with clinical,
      endoscopic, and histologic variables. METHODOLOGY: S-PIIINP and S-laminin were
      measured in 222 consecutive inflammatory bowel disease patients, who were
      screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine
      hypofunction with the p-aminobenzoic acid test (215 patients). The patients with
      abnormal screening results were further scheduled for endoscopic retrograde
      cholangiopancreatography, liver biopsy, secretin test and ultrasound. RESULTS: S
      PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory
      bowel disease patients, respectively. The elevated levels of the fibrosis markers
      were associated with laboratory signs of either hepatobiliary or pancreatic
      disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel
      disease patients, 15 of whom had primary sclerosing cholangitis. The median
      levels of S-PIIINP and S-laminin were significantly higher in patients with
      hepatobiliary disease than in those without (P < 0.0001 and P < 0.001,
      respectively), being most strikingly elevated in primary sclerosing cholangitis.
      Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels
      of S-PIIINP and S-laminin were also significantly associated with low values in p
      aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05)
      tests, but not with inflammatory bowel disease category, endoscopic or
      histological disease extent, frequency of bowel resection or actual clinical
      activity. CONCLUSIONS: In inflammatory bowel disease, increased S-PIIINP and S
      laminin are associated with hepatobiliary and pancreatic disorders.

PMID- 11995462
TI  - Histological findings after placement of a self-expanding stent in rectal
      carcinoma with complete obstruction--case report.
AB  - Patients with acute obstruction due to colorectal carcinomas frequently require
      emergency surgery. However, such emergency procedures are associated with various
      complications, a high mortality rate and a poor prognosis. If the obstruction
      could be immediately relieved, the patient could later undergo an elective
      operation with a much better prognosis. Recently, expanding metallic stents have
      been used to treat obstruction due to colorectal carcinoma. In the case reported
      here, we initially inserted a colonoscopic retrograde bowel drainage tube per
      anus to achieve decompression. We then placed a self-expanding metallic stent,
      since we anticipated a prolonged preoperative period due to high fever,
      congestive heart failure, cerebral infarction, and persistent high blood sugar
      concentrations. The patient had no complications for 57 days after placement of
      the stent, and eventually underwent an elective operation. Histologically, the
      side of the cancerous lesion compressed by the stent was thin and consisted
      solely of a serosal layer. Implantation of a metallic stent is safe for the
      treatment of acute malignant obstruction. Stent placement is indicated not only
      as a palliative treatment for inoperable or recurrent cases, but also as a
      preoperative procedure before elective surgical resection.

PMID- 11995463
TI  - Early elective surgery for bleeding ulcer in the posterior duodenal bulb. Own
      results and review of the literature.
AB  - BACKGROUND/AIMS: Acute upper gastrointestinal bleeding represents the major,
      potentially life-threatening complication of gastroduodenal ulcer disease with an
      average mortality of 10%. To decrease mortality a risk-dependent combined
      endoscopic and operative approach for the treatment of bleeding ulcer in the
      posterior duodenal wall was developed. METHODOLOGY: Between 1998 and 2000 in our
      hospital a total of 22 patients with bleeding posterior duodenal bulb ulcer were
      treated following a differentiated endoscopic-surgical concept. High-risk
      patients with high bleeding activity (n = 8) underwent early elective surgery
      after primary endoscopic treatment of the bleeding and stabilization of the
      patient in an intensive care unit. The management of patients presenting a low
      risk profile (n = 14) included careful surveillance and a consecutive second
      endoscopy 24 hours after the initial endoscopy. RESULTS: Patients that underwent
      surgery showed more severe secondary diseases than patients of the endoscopic
      group. Hemoglobin concentration in patients requiring surgery was significantly
      lower, they showed a higher incidence of hypovolemic shock and received more
      blood transfusions within the first 24 hours. Mortality was 0% in both groups, a
      relevant rebleeding occurred in one patient after endoscopic therapy, which was
      successfully treated by reendoscopy with fibrin injection. CONCLUSIONS: Due to
      these results as well as results of other groups we recommend early elective
      surgery in high-risk patients with bleeding duodenal bulb ulcer after primary
      endoscopic treatment of the bleeding.

PMID- 11995464
TI  - Topographical distribution of lymph node metastasis in adenocarcinoma of the
      gastroesophageal junction.
AB  - BACKGROUND/AIMS: The current discussion concerning the extent of resection in
      patients with adenocarcinoma of the gastroesophageal junction is focused beside
      the luminal extent of resection primarily on the value of lymphadenectomy.
      METHODOLOGY: In order to clarify whether spread of lymph node metastasis shows
      different pathways in adenocarcinomas of the gastroesophageal junction, a
      prospective, morphological study of the topographical distribution of lymph node
      metastasis was performed. Transthoracic en bloc esophagectomy with two-field
      lymphadenectomy (n = 13) or transhiatal esophagectomy with lymphadenectomy of the
      lower mediastinum and compartment I (lymph node No. 1-3) as well as II (n = 4)
      was performed in type I carcinoma and transhiatally extended gastrectomy with D2
      lymphadenectomy and lymphadenectomy of the lower mediastinum in type II and III
      carcinoma (n = 33). RESULTS: In 50 specimens, 1730 lymph nodes were evaluated
      with regard to metastatic infiltration. We found metastases in the lymph nodes of
      the lower mediastinum in 24% of type I carcinoma, in 11% of type II carcinoma and
      in 13% of type III carcinoma, whereas the lymph nodes of the upper mediastinum
      were tumor free in all patients with transthoracic en bloc resection and 2-field
      lymphadenectomy (n = 13). In all cases with lymph node metastasis abdominal lymph
      nodes were affected independently from the localization of the primary tumor.
      CONCLUSIONS: The main direction of lymph node spread in adenocarcinoma of the
      gastroesophageal junction is towards the abdomen and the lower mediastinum. For
      precise tumor staging standardized lymphadenectomy of the lower mediastinum and
      the abdominal compartments I and II is essential.

PMID- 11995465
TI  - Primary prophylactic therapy of esophageal varices--a literature review.

PMID- 11995466
TI  - Systemic factors are trophic in Thiry-Vella loop in the absence of luminal
      contents.
AB  - BACKGROUND/AIMS: Mucosal histology, crypt cell proliferation and brush border
      enzymes were measured in rats with varying degrees of Thiry-Vella fistulas, in
      order to compare the effect of systemic and luminal factors on adaptive growth
      and differentiation (brush border enzymes) in small intestinal epithelium.
      METHODOLOGY: Twenty-four male Wistar rats (300-350 g) were divided with three
      groups of eight which underwent the following operations: 20% Thiry-Vella
      fistula, 80% Thiry-Vella fistula and sham operation. RESULTS: 80% Thirty-Vella
      fistulas caused a functional short gut; in intestine remaining in continuity
      there were significant increases in segmental weight, protein, Alp activity and
      villus height, compared with sham-operated controls and 20% Thiry-Vella fistulas.
      There was a significant fall in villus height, crypt cell production in loops of
      20% Thiry-Vella fistula rats not exposed to luminal contents compared with
      control segments of sham-operated rats. In contrast, loops of the 80% Thiry-Vella
      fistula rats were not atrophied despite the much greater distance from luminal
      nutrients; the villus height and PCNA-LI were higher than in 20% Thiry-Vella
      fistula rats, and at least as great as in sham-operated rats. CONCLUSIONS: This
      study indicates that atrophy does not occur in loops after 80% Thiry-Vella
      fistula because crypt cell proliferation is maintained in Thiry-Vella fistulas.
      Thus, the atrophic effect of diversion of luminal nutrients can be counteracted
      by systemic growth factors released as part of the adaptive response; luminal
      factors are not essential for maintenance of normal cellular turnover when there
      is a powerful stimulus to cell proliferation.

PMID- 11995467
TI  - Role of bile acids in lymphocytic colitis.
AB  - BACKGROUND/AIMS: A high prevalence of bile acid malabsorption and a high response
      rate to bile acid binders are seen in collagenous colitis. Our aim was to explore
      if bile acids play a role in lymphocytic colitis, which is unknown. METHODOLOGY:
      Patients with lymphocytic colitis completed a diagnostic program, including the
      75SeHCAT (75Se-labelled homocholic acid-taurine) test and registration of
      symptoms. Prevalence of bile acid malabsorption, response to bile acid binders,
      correlation between 75SeHCAT and histopathology were determined. The 75SeHCAT
      values were compared with 29 controls. RESULTS: Two out of 23 with lymphocytic
      colitis had a 75SeHCAT retention < or = 10%. The median 75SeHCAT value in
      lymphocytic colitis, 24% (range: 1.7-53), was lower than in the control group,
      38% (range: 8-91) (P < 0.02). Forty-six per cent (6/13) responded to bile acid
      binders. No correlation was found between the 75SeHCAT values and degree of
      colonic inflammation. Two patients developed collagenous colitis. CONCLUSIONS:
      Bile acid malabsorption is more uncommon in lymphocytic colitis than in
      collagenous colitis. The 75SeHCAT values, however, suggest a role of bile acids
      in lymphocytic colitis. The conversion of 2 patients to collagenous colitis and
      disturbed absorption of bile acids also in lymphocytic colitis is consistent with
      the idea that the two forms represent variants of the same disease.

PMID- 11995468
TI  - Midazolam sedation for upper gastrointestinal endoscopy: comparison between the
      states of patients in partial and complete amnesia.
AB  - BACKGROUND/AIMS: The amnesia produced by anesthesia is advantageous for
      unpleasant procedures like gastroscopy, and midazolam is one of the most commonly
      used anesthesias for endoscopy. However the proper use of midazolam from the
      viewpoint of complete amnesia has been discussed very little. METHODOLOGY: One
      hundred and thirty-three unselected patients about to undergo upper
      gastrointestinal endoscopy were premedicated with sufficient intravenous
      midazolam to cause enough sedation so that no response was evoked when calling
      their name. Pulse, arterial pressure, arterial oxygen saturation and the physical
      signs of patients were recorded continuously during the procedures. After the
      study, patients were given 0.25 mg of flumazenil and asked if they could recall
      the procedures. Those who could recall even part of the procedure were not
      regarded as achieving complete amnesia. The efficacy of the sedative was judged
      by the appearance of complete amnesia. RESULTS: From our regression analysis
      complete amnesia was achieved in 75.9% of the total patients. The differences of
      the blood pressure fall, pulse rate increase and arterial oxygen saturation fall
      between the patients with complete and partial amnesia were minute and did not
      cause serious complications. Regression analysis revealed the most important
      factors for the complete amnesia to be midazolam dose per body weight and
      habitual hypnotic use. CONCLUSIONS: There are no obvious disadvantages to
      producing complete amnesia with midazolam for upper gastrointestinal endoscopy.
      Habitual hypnotic use along with midazolam dose per body weight is the most
      influencing factor for that purpose.

PMID- 11995469
TI  - Clinical application of argon plasma coagulation in endoscopic hemostasis for non
      ulcer non-variceal gastrointestinal bleeding--a pilot study in Taiwan.
AB  - BACKGROUND/AIMS: Argon plasma coagulation is an innovative non-touch
      electrocoagulation technique. A broad spectrum of indications has been proposed
      for argon plasma coagulation since its introduction into endoscopy in 1991. The
      aim of this study is to evaluate the efficacy of utilizing argon plasma
      coagulation in the endoscopic hemostasis of non-ulcer, non-variceal
      gastrointestinal bleeding in Taiwan. METHODOLOGY: A total of 26 consecutive
      patients (15 men, 11 women; mean age: 67.6 years) underwent argon plasma
      coagulation treatment between May 1999 and August 2000. Causes of bleeding
      included angiodysplasia in 3, tumor bleeding in 8, radiation colitis in 11,
      watermelon stomach in 1, Osler-Weber-Rendu syndrome in 1, and post-intervention
      in 2. Argon plasma coagulation was performed in 2 patients with bleeders in the
      esophagus, 10 in the stomach, 1 in the stomach and duodenum, and 13 in the colon.
      RESULTS: A total of 38 sessions of application in 26 patients were performed.
      Successful endoscopic argon plasma coagulation treatment was achieved in 21
      (80.8%) patients. Neither complication nor mortality related to argon plasma
      coagulation was observed in these 26 patients. CONCLUSIONS: Argon plasma
      coagulation is a safe, efficacious, and low-cost hemostatic modality for non
      ulcer, non-variceal gastrointestinal bleeding. It is mandatory to establish a
      comparative trial with other treatment modalities with a longer follow-up in the
      future.

PMID- 11995470
TI  - Significance of SIRS score in therapeutic strategy for acute appendicitis.
AB  - BACKGROUND/AIMS: The surgical indication for acute appendicitis has been
      discussed diversely. SIRS (systematic inflammatory response syndrome) is a
      concept that has been advocated as the clinical criteria on inflammatory
      diseases. The aim of the current study was to elucidate the significance of SIRS
      score in deciding therapeutic strategies for acute appendicitis. METHODOLOGY: One
      hundred and twenty-five patients who were admitted with the diagnosis of acute
      appendicitis were investigated in the current study. The ultimate surgical
      indication was decided by the physical examination done by the surgeons. Fifty
      nine patients were indicated for appendectomy. The relationship between decision
      for the surgical treatment for acute appendicitis and SIRS score/positive status
      was investigated. RESULTS: SIRS score of the patients who were treated with
      appendectomy was significantly higher than that of the patients treated with
      conservative therapy containing starvation and administration of antibiotics
      therapy and SIRS positive status in patients treated with appendectomy was also
      higher than that in patients with conservative therapy. CONCLUSIONS: SIRS score
      is also useful as objective and auxiliary information to determine the surgical
      indication for acute appendicitis.

PMID- 11995471
TI  - Morbidity of laparoscopic fundoplication for gastroesophageal reflux: a
      retrospective study about 1470 patients.
AB  - BACKGROUND/AIMS: The aim of this retrospective study was to report and quantify
      the immediate and 3-year complications after laparoscopic anti-reflux surgery in
      order to understand the mechanism. METHODOLOGY: From 1992 to 1996, 1470
      laparoscopic fundoplications were performed for symptomatic gastroesophageal
      reflux disease. Preoperative checkup included upper gastrointestinal tract
      endoscopy in 1437 patients (97.7%), esophageal manometry in 934 patients (63.5%),
      and 24-hour pHmetry in 799 patients (54.3%). Three procedures were performed:
      Nissen (n = 655), Nissen-Rossetti (n = 423), and Toupet (n = 392). The results
      were estimated at 1 and 3 months; thereafter they were evaluated at 3 years.
      Patients unable to return to the hospital center were contacted by telephone.
      RESULTS: Mean length of hospital stay was 4.6 days (range: 2-48 days). The
      preoperative complication rate was 2.1% (n = 31). The postoperative morbidity and
      mortality rates were 2.9% (43 patients) and 0.07% (1 patient), respectively.
      Conversion rate to laparotomy was 6.5% (96 patients). At 3 months, 87 patients
      (5.9%) had invalid dysphagia but there was no difference between the 3
      procedures. Twelve patients have been reoperated (0.8%). At 3 years, 78 patients
      (5.6%) presented a clinical recurrence. The rate of dysphagia was 0.35%, and 38
      patients were reoperated. CONCLUSIONS: Laparoscopic fundoplication is safe and
      effective with a low morbidity and mortality rate if junior surgeons commenced
      this procedure under the direct supervision of an experienced surgeon. Despite
      the advantage of this technique, we believe that indications for surgical
      management remain unchanged in the laparoscopic era.

PMID- 11995472
TI  - Hepatic volumetry to predict adverse events in percutaneous ablation of
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: This study aimed to clarify the relation of hepatic volumetry to
      adverse events after percutaneous transhepatic ablation for hepatocellular
      carcinoma. METHODOLOGY: One hundred and forty-nine patients with hepatocellular
      carcinoma who underwent percutaneous ablation sessions with complete ablation of
      cancer nodules, underwent volume measurement of the entire liver, tumor, and
      ablated area using computed tomography. The parenchymal ablation rate was
      calculated: (ablated volume-tumor volume)/(entire liver volume-tumor volume) x
      100 (%). Other clinical parameters were also analyzed to determine their
      relationship to adverse events. RESULTS: The median adjusted liver volume was 591
      mL/body surface area (m2) (range: 300 to 1197 mL/m2). The median parenchymal
      ablation rate was 2.3% (range: 0.2% to 20.2%). Adverse events were observed in 17
      patients after percutaneous ablation: liver abscess in 3, hepatic infarction in
      3, portal vein thrombus in 3, hemobilia in 1, pleural effusion and/or ascites in
      6, and gastric ulcer in 1. Multivariate analysis showed that Child B or C (P =
      0.0009), adjusted liver volume < 600 mL/m2 (P = 0.0004), and parenchymal ablation
      rate > 5% (P = 0.0320) were independent risk factors for adverse events.
      CONCLUSIONS: Measurement of liver volume and parenchymal ablation rate are useful
      to predict the presence of percutaneous ablation-related adverse events.

PMID- 11995473
TI  - The effect of ischemia on the regeneration of the cholestatic liver. An
      experimental study.
AB  - BACKGROUND/AIMS: Cholestatic liver is known to be more susceptible to ischemia
      than normal liver. In this study we assessed the histopathologic features of
      hepatic ischemic damage and liver regeneration in rats with experimental
      obstructive jaundice. METHODOLOGY: The study comprised 90 male Wistar rats. These
      were assigned randomly to 4 groups according to the surgical procedure they
      underwent: I (n = 10) controls (non-operated), II (n = 10) sham-operated, III (n
      = 30) occlusion of hepatic artery and portal vein (total liver ischemia), and IV
      (n = 40) ligation and division of the common bile duct ligation. Rats of group
      III were sacrificed 15 (IIIa), 30 (IIIb) and 60 min (IIIc) after total liver
      ischemia was done. Ten days after bile duct ligation, 10 rats of group IV
      underwent euthanasia, whereas the remaining 30, underwent total liver ischemia
      and were sacrificed after 15 min (IVb), 30 min (IVc), and 60 min (IVd). Liver
      wedge biopsies (left anterior lobe) were obtained and histologic examination
      included hematoxylin and eosin, and immunohistochemical stains for cytokeratin
      AE1, HEPPAR (hepatocyte paraffin antigen), and antigen Ki67. Immunohistochemical
      results for Ki67 were expressed following morphometric analysis. RESULTS: Liver
      sections from category IVa showed large duct obstruction features, and those from
      group III, ischemic chages including centrilobular hepatocellular swelling and
      necrosis, hepatocanalicular cholestasis, and mild portal mononuclear/mixed
      inflammation. Sections from groups IVB, IVc, IVd displayed together changes of
      large duct obstruction and ischemia, and in categories IVc (bile duct ligation
      +30 min total liver ischemia), and IVd (bile duct ligation +60 min total liver
      ischemia) necrosis of the large bile ducts was present. The total liver
      parenchymal area affected (% necrosis) was higher in categories IVd, and IVc
      compared to categories IVb (P < 0.05), and IIIc, IIIb, IIIa (P < 0.01). All 60
      total liver ischemia-liver biopsies, developed features of liver regeneration
      that originated from zone 2, extended to zone 1 and occasionally to zone 3.
      Immunohistochemical stains revealed cells positive to AE1 and cells positive to
      HEPPAR. Proliferation rate (% Ki67+ cells) was higher in category IIIa compared
      to categories IIIb, IIIc, IVb, IVc, and IVd (P < 0.05). CONCLUSIONS: Our study
      shows that liver ischemia induces more severe hepatocyte damage in livers with
      obstructive cholangiopathy compared to normal ones. Liver regenerative process is
      mediated mainly by proliferation of non-necrotic cells that express
      hepatocellular or ductular epithelial features. Proliferation rate of hepatocytes
      is lower when liver ischemia and obstructive jaundice coexist.

PMID- 11995474
TI  - Usefulness of 3-dimensional computed tomography for caudate lobectomy by
      transhepatic anterior approach.
AB  - BACKGROUND/AIMS: Improvement of precision and safety of resection of caudate lobe
      by the transhepatic anterior approach using preoperative 3-dimensional computed
      tomography. METHODOLOGY: The 3D-computed tomography images of 32 patients who
      underwent hepatectomy for hepatocellular carcinoma and metastatic tumors were
      reviewed. The usefulness of 3D-computed tomography was assessed on the basis of
      its depiction of the portal branch distribution of the caudate lobe and of the
      position of the parenchymal division plane in the transhepatic anterior approach.
      RESULTS: 1) Number of portal vein branches in the caudate lobe: 1 to 5 (average,
      2.75) portal vein branches were detected in the caudate lobe at the optimal angle
      (left-posterior 135 degrees) by 3D-computed tomography: P1l-sup in 84.3%, P1r-sup
      in 71.9%, P1r-inf in 71.9%, P1l-med in 15.6% and P1-trunk in 3.1%. 2). We
      classified the structure of the caudate lobe into four types, one type having two
      subtypes, based on the 3D-computed tomography findings of its portal branch
      distribution: Type 1: presence of 1rs, 1ri, 1ls; Type 2a: absence of 1ri; Type
      2b: absence of 1rs; Type 3: absence of 1ls; Type 4: presence of 1t alone. Type 1
      was observed in 16 of the 32 patients (50.0%), type 2a in 4 (12.5%), type 2b in 8
      (25.0%), type 3 in 3 (9.4%) and type 4 in 1 (3.1%). 3) When the tributary of the
      right hepatic vein draining segment 5 (RV5) can be detected (type 1: 81.3%), the
      right surface of the middle hepatic vein should be exposed; whereas its left
      surface should be exposed when RV5 cannot be detected (types 2 and 3: 18.7%).
      CONCLUSIONS: Preoperative 3D-computed tomography images enable more accurate
      diagnosis of intrahepatic tumor location and facilitate detection of the portal
      veins of the caudate lobe, thus simplifying both caudate lobectomy and the
      selection of which side of the division plane and of the middle hepatic vein to
      divide the liver parenchyma in the transhepatic anterior approach, and allowing
      complete preservation of the circulation of the remnant liver.

PMID- 11995476
TI  - Clinical studies of new material for portal vein embolization: comparison of
      embolic effect with different agents.
AB  - BACKGROUND/AIMS: Study of he embolic materials is necessary to select those
      suitable for preoperative portal embolization which increases the safety of
      hepatectomy. METHODOLOGY: Twenty-three patients with biliary tract cancer and
      hepatic tumor underwent portal embolization of the right portal vein. Four kinds
      of embolic materials were used. Gelatin sponge was used in 9, cyanoacrylate in 4,
      fibrin glue in 2, and gelatin sponge with polidocanol in 8 patients. The embolic
      effect in inducing hypertrophy as well as the surgical results were compared for
      different embolic agents. Left lobe hypertrophy was evaluated by computed
      tomography volume before and 2 weeks after portal embolization. RESULTS: With
      gelatin sponge, the volumetric increase was 21.9%, compared to 25% with
      cyanoacrylate, 13.5% with fibrin glue, and 35.3% for gelatin sponge with
      polidocanol. The volume increase of gelatin sponge with polidocanol was superior
      to those of other agents. In 18 of the 21 patients, hepatectomies with/without
      pancreaticoduodenectomy were performed. In 11 patients using the first 3 of the
      above-mentioned agents, 2 operative procedures were changed to limited hepatic
      resection, and 3 patients died of hepatic failure due to insufficient
      hypertrophy. Seven patients for whom gelatin sponge with polidocanol was used
      underwent the proposed operations with good results. CONCLUSIONS: Gelatin sponge
      with polidocanol induced sufficient hypertrophy and was the most suitable agent
      for portal embolization.

PMID- 11995475
TI  - Serum interleukin-6 and hepatocyte growth factor levels in patients after
      hepatectomy.
AB  - BACKGROUND/AIMS: To examine whether serum hepatocyte growth factor and
      interleukin-6 levels are early parameters of postoperative liver dysfunction
      after hepatectomy. METHODOLOGY: The serum levels of hepatocyte growth factor and
      interleukin-6 were measured in 16 hepatectomized patients on the day of surgery
      (before surgery, immediately after hepatectomy, after completion of surgery) and
      on postoperative days 1, 3, and 5. Serum liver function tests were determined for
      14 days after surgery and their results were correlated with serum interleukin-6
      and hepatocyte growth factor levels. RESULTS: Serum interleukin-6 and hepatocyte
      growth factor levels were elevated after surgery and these values were higher in
      patients who underwent hepatectomy greater than lobectomy in magnitude. The mean
      maximum value of interleukin-6 appeared on day 0 and was earlier than that of
      hepatocyte growth factor, which was found on day 1. Serum total bilirubin and
      alanine aminotransferase levels reached the maximum within 5 days after surgery.
      Multiple regression analysis showed that serum levels of interleukin-6 and
      hepatocyte growth factor on day 0 after surgery were significantly correlated
      with the postoperative maximum total bilirubin level (P < 0.0001). The maximum
      interleukin-6 level but not hepatocyte growth factor significantly correlated
      with the postoperative maximum bilirubin level (P < 0.02). CONCLUSIONS: Both the
      serum interleukin-6 and hepatocyte growth factor levels are likely early
      indicators of postoperative liver dysfunction in patients after hepatectomy.

PMID- 11995477
TI  - Simple blood tests can predict compensated liver cirrhosis in patients with
      chronic hepatitis C.
AB  - BACKGROUND/AIMS: Twenty to fifty percent of patients with chronic hepatitis C
      virus infection will insidiously progress to cirrhosis after 10-20 years' follow
      up. The aim of this study is to retrospectively evaluate the role of simple non
      invasive blood tests in detecting the presence of compensated liver cirrhosis in
      Chinese patients with chronic hepatitis C. METHODOLOGY: One hundred and eleven
      biopsy-proven chronic hepatitis C patients were enrolled, 23 (20.7%) patients
      showed cirrhosis with class A in Child-Pugh's classification and were all
      asymptomatic. Liver biochemistry, complete blood count, and serum N-terminal
      propeptide of type III procollagen were determined and then compared between
      chronic hepatitis C patients with compensated cirrhosis and without cirrhosis.
      Multivariate logistic regression analysis was used to predict factors associated
      with compensated cirrhosis. RESULTS: Multivariate logistic regression analysis
      showed platelet count < or = 140,000/mm3 (odds ratio: 23.44, P < 0.001),
      globulin/albumin ratio > or = 1 (odds ratio: 31.47, P = 0.008), and AST/ALT ratio
      > or = (odds ratio: 6.58, P = 0.035) were significant predictors associated with
      hepatitis C virus-related compensated cirrhosis. Platelet count < or =
      140,000/mm3 had 83% sensitivity and 85% specificity in detecting liver cirrhosis.
      Globulin/albumin ratio > or = 1 had 43% sensitivity, 98% specificity and AST/ALT
      ratio > or = 1 had 39% sensitivity, 92% specificity in detecting liver cirrhosis.
      Combined tests with AST/ALT > or = 1 and globulin/albumin > or = 1, platelet
      count < or = 140,000/mm3 and globulin/albumin > or = 1 had 100% specificity, 100%
      positive predictive value but lower sensitivity (22% and 39% respectively), lower
      negative predictive value (83% and 86%, respectively) in detecting hepatitis C
      virus-related compensated liver cirrhosis. CONCLUSIONS: Simple blood tests with
      platelet count < or = 140,000/mm3, globulin/albumin ratio > or = 1, and AST/ALT
      ratio > or = 1 can indicate liver cirrhosis in follow-up patients with chronic
      hepatitis C.

PMID- 11995478
TI  - Genome aberrations observed by restriction landmark genome scanning analysis of
      chromosomal DNA in various types of primary hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The genes responsible for hepatocellular carcinoma have not been
      identified. To identify the relevant genes of hepatocellular carcinoma, detailed
      and comprehensive information of genomic aberrations must be obtained. To reveal
      the chromosomal aberrations in hepatocellular carcinoma, we carried out a
      restriction landmark genome scanning analysis of various types of hepatocellular
      carcinoma. METHODOLOGY: Samples of various types of hepatocellular carcinoma,
      including two with multinodular-hepatocellular carcinomas, one hepatocellular
      carcinoma showing nodules in a nodule pattern, one hepatocellular carcinoma
      metastasized to different tissues, three small (< 2.0 cm) hepatocellular
      carcinomas and four large (> 5.0 cm) hepatocellular carcinomas were examined by
      the restriction landmark genome scanning method with corresponding non
      hepatocellular carcinoma tissues. Restriction enzyme Not I was used as a landmark
      enzyme, Eco RV was used as a fragmentation enzyme, and Hin fI was used as a
      digestion enzyme in the gel for two-dimensional electrophoresis. RESULTS: We
      observed spot aberrations with different origins. Frequently observed spot
      aberrations originated from the change in the methylation status of repetitive
      sequences. No clear correlation between the pathological grade and the number or
      type of spot aberrations was observed. CONCLUSIONS: We demonstrated that major
      aberrations of restriction landmark genome scanning spots originated from the
      change of methylation status in hepatocellular carcinoma.

PMID- 11995479
TI  - Regional and general effects of hepatic lobes with impaired blood flow after
      hepatic resection.
AB  - BACKGROUND/AIMS: In hepatic surgery, blood flow to some parts of the liver may
      become impaired. At present, no consensus has been reached on ways to treat such
      affected parts of the liver with impaired blood supply. METHODOLOGY: After the
      ligation of branches of rat's hepatic artery and/or portal vein, the ligated and
      non-ligated lobes were studied at fixed intervals up to 84 days. Parameters
      include hepatic tissue blood flow assessed by a laser Doppler flowmeter, liver
      regeneration ability using bromodeoxyuridine, apoptosis using anti-single
      stranded DNA Ig-G antibody, and vulnerability to an endotoxic injection. RESULTS:
      Hepatic artery ligation group showed no obvious changes in either the ligated or
      non-ligated lobes, and these lobes had no effects on the whole body. Of the
      portal vein ligation group, although the ligated lobes underwent marked atrophy,
      the compensatory hypertrophy of the non-ligated lobes took place sufficiently and
      no life-threatening conditions were observed. With regard to the hepatic
      artery/portal vein ligation (HA/PVL) group, hepatic blood flow in the ligated
      lobes rapidly decreased, and all hepatocytes underwent necrosis 1 day after
      surgery. In the non-ligated lobes, however, significant increases in the
      bromodeoxyuridine labeling index were detected at 1, 2, and 3 days after surgery,
      and compensatory hypertrophy was recognized. Indocyanine green 15-minute
      retention rate rapidly increased 1 day after surgery, and there were significant
      differences compared to the sham group up to 7 days after surgery. The
      postsurgical mortality rate in the HA/PVL group was significantly high at 13%,
      and mortality rate following endotoxin injection was as high as 75%. CONCLUSIONS:
      Affected parts of the liver with blockage of both the hepatic artery and portal
      vein should be resected.

PMID- 11995480
TI  - Quality of life after hepatectomy in patients with hepatocellular carcinoma:
      implication of change in hepatic protein synthesis.
AB  - BACKGROUND/AIMS: Surgical removal has been accepted as a therapeutic option for
      hepatocellular carcinoma. However, little is known about the quality of life
      after hepatectomy for hepatocellular carcinoma. In this report, we describe the
      risk factors most affecting impaired quality of life after partial hepatectomy in
      patients with hepatocellular carcinoma. METHODOLOGY: Ninety-six patients who
      received curative resections 12-60 months previously, answered our original
      questionnaire, mailed to them. The questions consisted of 14 items concerning
      physical function, social function, psychological function, physical sensation,
      and recognition of the disease, with a scoring system of 1, 2, and 3. Based on
      the pre- and postoperative serum alanine aminotransferase or cholinesterase
      levels at 3-month intervals during the follow-up period, the changes were
      classified into three types: those staying in the favorable or unfavorable range
      at one year (no change, Type 1 or Type 3), and those entering the unfavorable
      range postoperatively (Type 2). RESULTS: Total quality of life score: the sum of
      scores to questions 1-12, displayed two peaks of normal distribution. Based on a
      point of intersection of the two curves: i.e., score of 22, the patients were
      classified into 2 groups: those with preserved quality of life (n = 75) i.e.,
      total quality of life scores of 12-21, and impaired quality of life, scores of 22
      or more (n = 21). Older age (> or = 65 y) at hepatectomy, in the course of
      treatment for recurrence, and Type 2 change of serum cholinesterase level were
      associated with the impaired quality of life. Multivariate analysis revealed that
      Type 2 change of serum cholinesterase levels was an independent risk factor for
      an impaired quality of life. Furthermore, the patients exhibiting Type 2 change
      of serum cholinesterase levels were clearly impaired in their physical and social
      functions compared to the other patients. Hepatitis-related or cancer-related
      factors showed no correlation with the deterioration of the quality of life.
      CONCLUSIONS: The quality of life after hepatectomy in patients with
      hepatocellular carcinoma was impaired in cases of aged patients, treatment for
      recurrence, and Type 2 change of the serum cholinesterase level. Postoperative
      maintenance of protein synthesis including cholinesterase is one measure to
      preserve a satisfactory quality of life after hepatectomy.

PMID- 11995481
TI  - The biochemical and histopathological effects of ursodeoxycholic acid and
      metronidazole on total parenteral nutrition-associated hepatic dysfunction: an
      experimental study.
AB  - BACKGROUND/AIMS: Total parenteral nutrition causes many complications such as
      cholestasis. Ursodeoxycholic acid is used for the treatment of several
      cholestatic problems. Metronidazole was investigated before for preventing some
      components of total parenteral nutrition-associated hepatic dysfunction. This
      study was designed to investigate the effects of ursodeoxycholic acid alone and
      ursodeoxycholic acid + metronidazole combination on total parenteral nutrition
      associated cholestasis. METHODOLOGY: Eighteen rabbits were divided into three
      groups as follows: group A received a standard formula of total parenteral
      nutrition only, group B received total parenteral nutrition + ursodeoxycholic
      acid (3 mg/kg/day), and group C were given total parenteral nutrition +
      ursodeoxycholic acid + metronidazole (25 mg/kg/day) for eight days, respectively.
      Several parameters of liver function tests were compared among these groups.
      These were transaminases, alkaline phosphatase, total bilirubin, total
      cholesterol, triglycerides, and serum bile acids. Liver histology was detected in
      each group at the end of the experiment. RESULTS: In group A, total parenteral
      nutrition administration resulted in remarkably higher serum values of
      transaminases, alkaline phosphatase, total cholesterol, total bilirubin,
      triglycerides, and free bile acids whereas ursodeoxycholic acid administration
      showed important improvements in the serum values of these parameters in group B
      animals. The metronidazole group showed nearer or similar laboratory values with
      group B, but significant differences appeared in bilirubin values (P < 0.05)
      among these groups. Liver histology presented marked differences between group A
      and group B. Steatosis formed the main component of liver histology in 4 animals
      out of 6 in group A. Contrary to this, all of the specimens showed normal liver
      structure except one in group B. In the third group we did not see better
      morphology than in group B. CONCLUSIONS: These results suggested that oral
      ursodeoxycholic acid therapy during total parenteral nutrition reduces bilirubin
      levels and improves the other indicators of cholestasis and helps prevent
      disturbances of liver histology. When it is combined with metronidazole a
      significant decrease in bilirubin levels has been gained. With the help of
      ursodeoxycholic acid we can provide enterohepatic circulation of bile acids and
      regulate lipid metabolism. Metronidazole can be an antibiotic of choice during
      total parenteral nutrition when needed.

PMID- 11995482
TI  - Evaluation of portal vascular resistance using an intraoperative Doppler
      ultrasound.
AB  - BACKGROUND/AIMS: To evaluate portal vascular resistance using Doppler ultrasound
      intraoperatively. METHODOLOGY: We measured maximum flow velocities and pressures
      of umbilical portion of the left portal branch before and after clamping of the
      right main branch of the Glisson's sheath. We proposed a new index, simplified
      portal resistive index, that was the ratio of the difference of the portal venous
      pressure to the difference of maximum portal flow velocity. RESULTS: There were
      good correlations between portal vascular resistance and simplified portal
      resistive index. Simplified portal resistive index was found to become higher as
      fibrotic changes progressed, and there were significant differences between
      normal liver, chronic hepatitis, and liver cirrhosis. CONCLUSIONS: Simplified
      portal resistive index evaluated using intraoperative Doppler ultrasound is an
      easy and reliable index for assessing portal vascular resistance during liver
      surgery.

PMID- 11995483
TI  - Erythrocyte-binding polyamine as a tumor growth marker for human hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Polyamines are essential for cell proliferation,
      differentiation, and transformation. Concentrations of polyamines are higher in
      some cancer tissue than in normal tissue. We examined erythrocyte-binding
      polyamines to evaluate the usefulness of polyamines as pathophysiological markers
      for hepatocellular carcinoma. METHODOLOGY: We measured erythrocyte-binding
      polyamine levels in peripheral blood samples obtained from 51 normal adult
      controls, 136 patients with chronic viral hepatitis, 104 patients with viral
      hepatic cirrhosis, and 130 patients with hepatocellular carcinoma. RESULTS: We
      defined the concentration of spermidine plus spermine as the erythrocyte
      polyamine level, and designated the cut-off level for normal as the mean
      erythrocyte polyamine level +/- 2 SD in control. The erythrocyte polyamine level
      was abnormally elevated (positive) in 56 (43%) of 130 patients with
      hepatocellular carcinoma, 11 (8%) of 136 patients with chronic hepatitis, and 13
      (13%) of 108 patients with cirrhosis. The level was higher in patients with a
      short tumor doubling time. In 27 patients with tumors, there was negative
      correlation between tumor doubling time and erythrocyte polyamine level (r = 
      0.46; P = 0.0147). CONCLUSIONS: We conclude that erythrocyte polyamine may be a
      useful tumor growth marker in patients with hepatocellular carcinoma.

PMID- 11995484
TI  - Incidence of hepatocellular carcinoma in chronic hepatitis C after interferon
      therapy.
AB  - BACKGROUND/AIMS: We investigated the rate of occurrence and the risk factors for
      hepatocellular carcinoma in chronic hepatitis C patients who received interferon
      therapy. METHODOLOGY: We followed 413 chronic hepatitis C patients for more than
      6 years after interferon therapy and assessed the following patient
      characteristics: age, sex, platelet count, response to interferon, hepatitis C
      virus RNA level, hepatitis C virus genotype, liver histology, and changes in
      serum alanine aminotransferase levels. RESULTS: Hepatocellular carcinoma was
      found in 21 patients after interferon therapy. The factor most related to the
      occurrence of hepatocellular carcinoma was changes in serum alanine
      aminotransferase levels (univariate analysis, P < 0.0001; multivariate analysis,
      P = 0.0013), followed by age (univariate analysis, P = 0.0003; multivariate
      analysis, P = 0.0029). A significant difference was observed in the platelet
      count and response to interferon based on univariate analysis alone (P = 0.0096,
      P = 0.0241, respectively), however no significant differences were noted in the
      other factors. The course of serum alanine aminotransferase levels following
      interferon therapy rather than the eradication of hepatitis C virus was found to
      be the factor most profoundly involved in liver carcinogenesis. CONCLUSIONS: Even
      if interferon therapy fails to eradicate the hepatitis C virus, maintaining low
      serum alanine aminotransferase levels post-interferon therapy would reduce the
      risk of hepatocellular carcinoma in chronic hepatitis C.

PMID- 11995485
TI  - Percutaneous vs. surgical placement of hepatic artery indwelling catheters for
      regional chemotherapy.
AB  - BACKGROUND/AIMS: Intra-arterial hepatic chemotherapy based on floxuridine
      infusion is an effective treatment for hepatic metastases from colorectal cancer.
      The aim of the present study is the comparative analysis of surgical and
      percutaneous transaxillary approaches to implant a catheter into the hepatic
      artery for intra-arterial hepatic chemotherapy with floxuridine. METHODOLOGY:
      Fifty-six patients received an arterial device for intra-arterial hepatic
      chemotherapy. Twenty-eight patients (LPT group) underwent laparotomy to implant
      the catheter into the hepatic artery, the other 28 patients (PCT group) received
      a percutaneous catheter into the hepatic artery through a transaxillary
      percutaneous access. Safety and efficacy of surgical and percutaneous
      transaxillary approaches were comparatively analyzed in terms of number of intra
      arterial hepatic chemotherapy cycles administered, device-related complications
      causing suppression of intra-arterial hepatic chemotherapy, and biological costs
      of the procedures. RESULTS: Mean postoperative hospitalization was 8.2 +/- 2.2
      days in the LPT group and 1.8 +/- 0.7 days in the PCT group (P < 0.0001), while
      mean analgesic requirements were 9.7 +/- 3.2 doses in the LPT group and 2 +/- 0.9
      doses in the PCT group (P < 0.0001). Mean number of intra-arterial hepatic
      chemotherapy cycles administered was 6.5 +/- 4.2 in the LPT group and 4.3 +/- 3.4
      in the PCT group (P = 0.038). The overall incidence of device-related
      complications causing suppression of intra-arterial hepatic chemotherapy was
      42.7% in the PCT group and 7.1% in the LPT group (P = 0.005). CONCLUSIONS:
      Surgical implantation is still recommended when laparotomy has to be performed
      for other contextual procedures, such as colorectal or hepatic resection, while
      percutaneous transaxillary catheter placement is indicated for palliative or
      neoadjuvant intra-arterial hepatic chemotherapy.

PMID- 11995486
TI  - Hepatic resection for hepatocellular carcinoma in diameter of > or = 10 cm.
AB  - BACKGROUND/AIMS: Definitive efficacy of hepatic resection for hepatocellular
      carcinoma larger than or equal to 10 cm in diameter remains to be resolved.
      METHODOLOGY: The surgical outcomes in 33 consecutive patients with hepatocellular
      carcinoma in diameter of > or = 10 cm who underwent hepatic resection were
      retrospectively clarified. Postresection prognostic factors were evaluated by
      univariate and multivariate analysis using Cox's proportional hazards model.
      RESULTS: The overall incidence of postoperative complications was 39%, and 5
      patients among them had hospital deaths (15%) including 2 (6%) operative deaths.
      The 3-year, 5-year, and 9-year overall survival rates after hepatic resection
      were 32%, 27%, and 17%, respectively. Univariate analysis revealed that liver
      cirrhosis and stage IV-A (pTNM staging) were significant factors of poor overall
      survival. By Cox's proportional hazards model, liver cirrhosis was an
      independently unfavorable prognostic factor of long-term survival. Hospital
      mortality rate in patients with cirrhosis was 31%. The 5-year overall survival
      rate in patients with cirrhosis (7%) was significantly shorter than that in
      patients without cirrhosis (43%) (P = 0.006). In addition, the 5-year overall
      survival rate in patients with stage IV-A (11%) was significantly shorter than
      that in patients with stage II and III (48%) (P = 0.024). The incidence of stage
      IV-A in patients with cirrhosis (77%) was significantly higher than those without
      cirrhosis (35%) (P = 0.032). CONCLUSIONS: Hepatic resection for hepatocellular
      carcinoma in diameter of > or = 10 cm was effective for patients without liver
      cirrhosis and with stage II or III. Appropriate selection of the candidates for
      partial hepatectomy based on the above prognostic factors may play an important
      role in the improvement of high mortality rate and poor long-term survival for
      such patients. Prospective randomized trials are needed to define the role of
      hepatic resection for cirrhotic patients with large HCC.

PMID- 11995487
TI  - Acute hepatitis A virus infection: a review of prognostic factors from 25 years
      experience in a tertiary referral center.
AB  - BACKGROUND/AIMS: Hepatitis A is usually a mild, self-limiting illness but can
      result in severe or fatal disease. We reviewed 25 years experience to determine
      what factors predispose to severe or fatal disease. METHODOLOGY: We identified 97
      patients admitted between 1974-1999 with acute hepatitis A. Clinical, biochemical
      and histological data were correlated with outcome and patients were screened for
      evidence of hepatitis B or C virus coinfection and coexisting autoimmunity.
      RESULTS: Fifty-five patients had liver failure with hepatic encephalopathy of
      whom 29 died and 6 underwent liver transplantation. Patients with liver failure
      were significantly older than those without (mean age: 42.2 +/- 13.3 vs. 29.2 +/-
      7.8, P = 0.0001), and liver failure patients who died were older than those
      surviving (47.5 +/- 12.7 vs. 36.3 +/- 11.6, P = 0.0001). Hyperacute liver failure
      predicted good outcome (P = 0.0001). Three patients with viral coinfection had
      established cirrhosis and died. Detectable autoantibodies did not correlate with
      outcome or severity. Patients acquiring infection abroad were more likely to have
      liver failure than those acquiring infection in the UK (P = 0.023). CONCLUSIONS:
      Age is the best predictor for outcome in patients with liver failure from
      hepatitis A. Underlying chronic liver disease, and the time of onset of
      encephalopathy are also factors affecting outcome. Infection acquired abroad has
      a worse prognosis.

PMID- 11995488
TI  - Dietary iron restriction improves aminotransferase levels in chronic hepatitis C
      patients.
AB  - BACKGROUND/AIMS: It is generally accepted that iron overload plays an important
      role in the pathogenesis of liver cell injury in chronic hepatitis C. The present
      study was undertaken to evaluate whether low-iron diet improves liver function
      tests in patients with chronic hepatitis C. METHODOLOGY: Seventeen patients with
      chronic hepatitis C (13 men and 4 women, 54 +/- 14 years old) that did not
      respond to, or were unsuitable for interferon therapy, were enrolled in this
      study. All patients had been pretreated with ursodeoxycholic acid for more than
      12 months before the beginning of the study. Dietary iron intake was restricted
      to less than 7 mg/day, and the patients were followed up for 18 months. RESULTS:
      Mean daily iron intakes, calculated from food records, were 5.9 and 6.4 mg after
      6 and 12 months, respectively. The mean serum ferritin decreased significantly
      from 362 ng/mL at entry to 179 ng/mL after 18 months. The serum unsaturated iron
      binding capacity level increased significantly from 163 micrograms/dL at entry to
      203 micrograms/dL after 18 months. The serum aspartate aminotransferase decreased
      significantly from 62 IU/L at entry to 47 IU/L after 18 months, and serum alanine
      aminotransferase from 68 IU/L at entry to 53 IU/L after 18 months. Serum iron,
      hepatitis C virus-RNA titer and platelet count remained unchanged throughout the
      study. CONCLUSIONS: These results suggest that iron-restricted diet may be an
      important therapeutic modality for improving liver injury in patients with
      chronic hepatitis C.

PMID- 11995489
TI  - Successful surgical control for hepatocellular carcinoma disseminated to the
      peritoneum: a case report.
AB  - Treatment for dissemination of hepatocellular carcinoma to the peritoneum has not
      yet been established. A case of a 62-year-old man who underwent curative
      resection for hepatocellular carcinoma 1 month after ultrasonically guided needle
      biopsy is presented. At 23 months after surgery, computed tomography revealed a
      mass in the abdominal cavity. At laparotomy 3 months later, a peritoneal tumor
      deposit directly invading the colon was resected in continuity with a portion of
      large intestine. The tumor was confirmed histopathologically to represent
      dissemination of hepatocellular carcinoma. No other lesions were detected 20
      months after the second operation. Surgical treatment can locally control
      peritoneally disseminated hepatocellular carcinoma provided that lesions have
      limited extent.

PMID- 11995490
TI  - Two-stage subtotal hepatectomy for metastatic adrenal adenocarcinoma, a case
      report.
AB  - Adrenal adenocarcinoma is a rare tumor with a poor prognosis. We present a case
      of recurrent adrenal adenocarcinoma with synchronous bilobar liver metastases
      that was treated by a two-stage subtotal hepatectomy. A formal right
      hemihepatectomy was performed with cryotherapy to a left lobe metastasis that was
      subsequently resected after a period of hepatic regeneration.

PMID- 11995491
TI  - Metabolic modulation by concomitant administration of insulin and glucagon in
      pancreatectomy patients.
AB  - BACKGROUND/AIMS: The metabolic kinetics after a total pancreatectomy, especially
      the postoperative loss of pancreatic endocrine function including insulin and
      glucagon secretions, remain unexplored. We examined the metabolic status of
      patients after a total pancreatectomy under insulin control and the effects of
      glucagon administration on metabolic kinetics. METHODOLOGY: The metabolic
      assessments of 11 patients who had undergone total pancreatectomy were performed
      using indirect calorimetry with blood amino acid and lipid analysis in the
      following three metabolic conditions: 1) under conventional insulin control
      alone, 2) when a pharmacologically active amount of glucagon was administered,
      and 3) when an additional amount of insulin was administered concomitantly to
      attain the insulin/glucagon molar ratio in the serum similar to the physiological
      value. RESULTS: Under conventional insulin control alone, the level of
      calorigenesis from proteins was decreased mainly due to an impairment in the
      utilization of glycogenic amino acids. Furthermore, carbohydrates were not
      sufficiently utilized, and lipid metabolism was increased as a result of the
      reduced lipid catabolism. When a pharmacologically active amount of glucagon was
      administered, the utilization of glycogenic amino acids and lipids increased.
      However, the utilization of carbohydrates was slightly reduced. When an
      additional amount of insulin was administered, an increased utilization of
      protein was observed. At the same time, marked improvement was observed in the
      utilization of carbohydrates which was reduced in 1) and 2) indicated above.
      Furthermore, the utilization of lipids in calorigenesis was not reduced, but it
      was reduced in lipid catabolism. CONCLUSIONS: The above findings indicate the
      importance of administering insulin and glucagon concomitantly and maintaining
      the blood insulin/glucagon ratio at a level similar to the physiological value
      regardless of the administered dosages of these two hormones in order to improve
      the energy and nutritional metabolism following a total pancreatectomy.

PMID- 11995492
TI  - The effects of prostaglandin E1 on the microperfusion of the pancreas during
      acute necrotizing pancreatitis in rats.
AB  - BACKGROUND/AIMS: In this study we investigated the effects of prostaglandin E1 on
      the microperfusion of the pancreas during acute necrotizing pancreatitis in rats.
      METHODOLOGY: Acute necrotizing pancreatitis was induced in rats by standardized
      intraductal bile acid infusion and cerulein hyperstimulation. Serum trypsinogen
      activation peptides were measured to verify comparable disease severity. After
      the induction of acute pancreatitis, animals randomly received either ringer
      lactate or prostaglandin E1. Monitoring included cardiorespiratory parameters,
      hematocrit, pancreatic oxygen tissue oxygen pressure, serum amylase and
      trypsinogen activation peptides. At the end of experiments pancreas was removed
      for evaluation of acinar cell injury. RESULTS: The two study groups were
      comparable with regard to mean arterial pressure, heart rate, arterial blood
      gases, hematocrit, and serum amylase. The induction of pancreatitis resulted in
      the significant decrease of pancreatic tissue oxygen pressure. In both groups the
      use of prostaglandin E1 did not change pancreatic tissue oxygen pressure despite
      of stable cardiorespiratory parameters, and serum amylase activity. Prostaglandin
      E1 decreased pancreatic damage and serum trypsinogen activation peptide level
      significantly. CONCLUSIONS: These results suggest that prostaglandin E1 had no
      effects on the improvement of microcirculation of pancreas, and had beneficial
      effects on the course of acute necrotizing pancreatitis.

PMID- 11995493
TI  - Carcinoma of the head of the pancreas.
AB  - BACKGROUND/AIMS: Extended radical surgery might provide a survival advantage for
      patients with carcinoma of the head of the pancreas. METHODOLOGY: Between January
      1980 and December 1999, 144 patients with carcinoma of the head of the pancreas
      were treated in a community hospital setting, of whom 69 patients who underwent
      radical surgery were retrospectively reviewed. Surgical procedures included
      standard pancreaticoduodenectomy (27 patients), pylorus-preserving
      pancreaticoduodenectomy (27 patients), and total pancreatectomy (15 patients).
      Portal vein resection was performed for 15 patients. Retroperitoneal
      lymphadenectomy was performed for 35 patients. No patients received adjuvant
      chemotherapy or radiotherapy. RESULTS: The surgical resection rate was 47.9% with
      a surgical mortality rate of 4.3% during this period. The overall 5-year survival
      rate after radical surgery was 16.1% with a median survival of 12 months. Seven
      patients survived five years, making 16.3% of the patients available for a more
      than 5-year follow-up. Long-term survivors had less than two positive lymph nodes
      in the posterior pancreatic head. Fourteen of 15 patients undergoing portal vein
      resection died within 21 months. One patient having no portal vein invasion
      microscopically survived 27 months without recurrence. CONCLUSIONS: Extended
      radical surgery did not prolong survival for patients with carcinoma of the head
      of the pancreas.

PMID- 11995494
TI  - Pancreatic juice output and amylase level in the drainage fluid after
      pancreatoduodenectomy in relation to leakage.
AB  - BACKGROUND/AIMS: The objective of this study was to clarify the relationship
      between the consistency of the pancreas and pancreatic anastomotic leakage after
      pancreatectomy. METHODOLOGY: Sixty-two patients who underwent proximal
      pancreatectomy with pancreaticoenterostomy were reviewed with regard to the
      consistency of the pancreas, size of the main pancreatic duct, postoperative
      pancreatic juice output, and pancreatic leakage after partial
      pancreatoduodenectomy. The pancreatic parenchyma was classified as having soft,
      intermediate and hard consistency (group 1, 2 and 3, respectively). Monitoring
      the output of pancreatic juice and amylase level in the drainage fluid after
      operation for the purpose of detecting of dehiscence of pancreaticoenterostomy.
      RESULTS: The mean pancreatic juice output during a period of 10 days
      (postoperative days 5 to 14) was 2446 +/- 27 cc in group 1 (n = 26), 846 +/- 13.5
      cc in group 2 (n = 19) and 460 +/- 8.1 cc in group 3 (n = 17). Anastomotic
      leakage occurred in four (15%) patients in group 1, three (15%) in group 2, and
      none in group 3. In patients with leakage, abrupt decrease or fluctuating output
      of pancreatic juice occurred and amylase level in the drainage fluid was more
      than 10,000 IU/L POD 7. CONCLUSIONS: Patients with a pancreatic parenchyma with
      an intermediate or normal consistency produced more pancreatic juice and had a
      higher leak rate. Monitoring the output of pancreatic juice and amylase level in
      the drainage fluid after operation may provide a clue to the detection of
      dehiscence of pancreaticoenterostomy.

PMID- 11995495
TI  - Regional chemotherapy-induced cure for pancreatic head carcinoma.
AB  - Pancreatic carcinoma has a devastating prognosis. The only hope for cure for many
      patients is still surgery while the disease is at the early stages. Chemotherapy
      (systemic/regional) or radiotherapy has been shown to be helpful in the
      palliation of the disease but not for cure. We reported a pancreatic head
      carcinoma, which was cured only by regional chemotherapy. To the best of our
      knowledge this is the first case in the literature.

PMID- 11995496
TI  - Carcinoma of pancreas presenting as a decrease in visual acuity.
AB  - Recent unilateral decrease in visual acuity of a 72-year-old woman was the
      background of a comprehensive medical investigation that led to the definitive
      diagnosis of metastatic pancreatic carcinoma. Visual improvement was achieved
      after ocular irradiation but the patient died two months later because of
      bilateral pneumonia and sepsis. Ocular metastasis from advanced carcinoma of
      various organs is well known and usually is an indicative sign of poor prognosis.
      Ocular metastases from pancreatic carcinoma are extremely rare, and to the best
      of our knowledge, it has not been reported previously in English. It should be
      emphasized that unilateral decrease in visual acuity must be thoroughly
      investigated.

PMID- 11995497
TI  - Signet-ring-cell carcinoma of the ampulla of Vater: a case report.
AB  - We encountered a rare variant of carcinoma of the ampulla of Vater in a 68-year
      old man with postprandial abdominal pain and nausea. Ultrasonography and computed
      tomography showed a dilated common bile duct and main pancreatic duct. At
      duodenoscopy, the papilla of Vater was enlarged, and biopsy specimens taken from
      the papilla revealed signet-ring-cell carcinoma. Endoscopic ultrasonography
      showed a hypoechoic tumor without pancreatic invasion. Pylorus-preserving
      pancreatoduodenectomy was performed. Histologic examination of resected specimens
      indicated lymphatic and vascular invasion, but surgical margins were tumor-free.
      The patient is alive and disease-free 10 months after the operation.

PMID- 11995498
TI  - Cardiac tamponade as a complication of pseudocyst in chronic pancreatitis.
AB  - Authors report a case of relapsing chronic calcifying pancreatitis with pleural
      and pericardial effusions during an episode of acute exacerbation. A large
      multilocular pancreatic pseudocyst expanded into the mediastinal space resulting
      in pericardial effusion that caused cardiac tamponade with severe circulatory
      deterioration. After resuscitation and pericardiocentesis a successful surgical
      procedure was performed, which produced rapid clinical improvement. Authors
      discuss this uncommon complication and review the proposed pathogenic mechanisms
      and possible therapeutic interventions.

PMID- 11995499
TI  - Splenic abscess: diagnosis and management.
AB  - BACKGROUND/AIMS: To evaluate the usefulness of a combination of computed
      tomography and sonography for splenic abscess diagnosis and management
      determination. METHODOLOGY: From January 1986 to June 1999, 30 patients of
      pyogenic splenic abscess were collected in our hospital. Computed tomograms of
      the spleen were performed on all of the patients, and abdominal sonographies were
      performed on 26 of them. The imaging findings of all the patients were reviewed
      with respect to the clinical presentations, predisposing factors, infective
      organisms, method of treatment and clinical outcome. RESULTS: The clinical triad
      of splenic abscess was the main presentation of the 30 patients; it included
      fever (92%), left upper abdominal pain (77%) and leukocytosis (66%). Infective
      bacteria were identified in 19 patients, and the most offending bacteria were
      aerobes (82.6%). The radiological findings included single abscess were found in
      16 patients and multiple abscesses were noted in 14 patients. The computed
      tomography and sonography findings included abnormal gas content (6 cases),
      progressive enlargement of lesion (6 cases), subcapsular extension of lesion (6
      cases), extracapsular fluid collection (8 cases) and cystic lesion (7 cases). 59%
      of the cases had at least one of the above imaging findings. With the combination
      of the clinical triad and the imaging findings, the diagnostic rate rose up to
      86.7%. CONCLUSIONS: Although splenic abscess is rare, it has a high mortality
      rate if there is delay in diagnosis and treatment. With the combination of
      computed tomography, sonography and clinical features, early diagnosis and
      treatment can be made. Percutaneous drainage for single abscess and splenectomy
      for multiple abscesses are the safe and effective treatment choice. The computed
      tomography and sonography appearance of splenic abscess is a valuable predictor
      of outcome of splenic abscess drainage. Medical treatment alone was definitely
      insufficient.

PMID- 11995500
TI  - Rapid urease test utility for Helicobacter pylori infection diagnosis in gastric
      ulcer disease.
AB  - BACKGROUND/AIMS: To establish rapid urease test utility for initial diagnosis of
      Helicobacter pylori infection in gastric ulcer patients and to determine the best
      site for sampling for gastric biopsies. METHODOLOGY: Seventy consecutive gastric
      ulcer patients were prospectively studied. All these patients underwent three
      biopsies from both antrum and body (two for hematoxylin-eosin staining and one
      for rapid urease test -Jatrox H. p. Test-). Likewise, IgG ELISA serology and 13C
      urea breath test were carried out. Gold standard for H. pylori infection was
      defined as two or more tests (i.e., histology, serology, breath test) with
      positive results. RESULTS: Rapid urease test yielded 96.8% sensitivity (95% CI =
      89-99%) and 100% (66-100%) specificity when using biopsy specimens from the body,
      with identical results when biopsy specimens from both antrum and body were
      considered together. However, when only biopsy specimens from the antrum were
      used, sensitivity dropped to 72.6% (60-82%) and specificity was 100% (66-100%).
      As far as concordance between rapid urease test and histology is concerned, we
      found a "proportion of positive agreement" of 0.78 for the antrum, with 0.46
      kappa statistic (P < 0.0001) and 15 McNemar statistic (P < 0.0001). For the
      gastric body, "proportion of positive agreement" was 0.98, with 0.94 kappa
      statistic (P < 0.0001) and 1 McNemar statistic (P = 0.3). Larger (P < 0.01)
      prevalence of both glandular atrophy (17.8%, 11-28%) and intestinal metaplasia
      (68.5%, 57-78%) was observed in the antrum in comparison with that in the body
      (4.1%, 1-11%; and 16.4%, 10-26%, respectively). CONCLUSIONS: Biopsy specimens
      from the body should always be obtained when the rapid urease test is performed
      to diagnose H. pylori infection in gastric ulcer, since this procedure is less
      accurate when biopsy specimens from the antrum are used, probably due to larger
      prevalence of both glandular atrophy and intestinal metaplasia in the latter
      site. Likewise, it seems that rapid urease test from body biopsies is sufficient
      to reach a reliable infection diagnosis in gastric ulcer patients as this
      procedure performed with antrum biopsies fails to improve its overall results.

PMID- 11995501
TI  - Quantitative correlation of Helicobacter pylori stool antigen (HpSA) test with
      13C-urea breath test (13C-UBT) by the updated Sydney grading system of gastritis.
AB  - BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection has a causative
      relationship with various gastrointestinal disorders. 13C-urea breath test and H.
      pylori stool antigen test are two valuable noninvasive tests for detecting H.
      pylori infection. Since the bacterial load of H. pylori in the stomach and the
      resulting severity of gastritis are important in validating the status of H.
      pylori infection, we would like to investigate the relative diagnostic accuracy
      of 13C-urea breath test and H. pylori stool antigen test with respect to the
      severity of gastritis. METHODOLOGY: The H. pylori statuses of 62 consecutive
      patients were evaluated by five tests, i.e., culture, histology, biopsy urease
      test, 13C-urea breath test, and H. pylori stool antigen test. Gastritis was
      graded by the updated Sydney system. H. pylori status was defined as positive
      when the culture was positive or the concordance of positivity of two of the
      other four tests. RESULTS: Thirty-five patients (56%) were H. pylori positive.
      The accuracy of H. pylori stool antigen test and 13C-urea breath test were 92.6%
      and 100%, respectively. There was a positive correlation between the level of
      delta 13CO2 of the 13C-urea breath test and the optical density value of enzyme
      immunoassay of the H. pylori stool antigen test (Rho = 0.758, P < 0.001). Both
      the level of delta 13CO2 of 13C-UBT and the optical density value of enzyme
      immunoassay of the H. pylori stool antigen test correlated well with the separate
      score of the density of H. pylori (P < 0.001, each) and the inflammatory activity
      (each P < 0.001). CONCLUSIONS: Both the 13C-urea breath test and H. pylori stool
      antigen test are effective non-invasive methods to detect the status of H. pylori
      infection with respect to correlation with the density of H. pylori and
      inflammatory activity of gastritis.

PMID- 11995502
TI  - Lymph node dissection in surgical treatment for remnant stomach cancer.
AB  - BACKGROUND/AIMS: Lymphatic flow and the incidence of lymph node metastasis in
      remnant stomach cancer after distal gastrectomy are obscure. There is consequent
      controversy about appropriate lymph node dissection in such cases. METHODOLOGY:
      Thirty-three consecutive patients with remnant stomach cancer and 44 consecutive
      patients primary gastric cancer in the upper third of the stomach were
      investigated retrospectively about lymphatic flow by injection of activated
      carbon particles, and about the incidence of lymph node metastasis. RESULTS:
      Lymphatic flow and the incidence of lymph node metastasis in remnant stomach
      cancer after distal gastrectomy without lymph node dissection were the same as
      those in primary gastric cancer in the upper third of the stomach. Lymphatic flow
      after distal gastrectomy with lymph node dissection frequently streamed toward
      the para-aortic lymph nodes through the lymph nodes along the greater curvature
      and the suprapancreatic lymph nodes. Lymphatic flow toward the jejunal and
      colonic mesentery was observed regardless of the method of reconstruction. This
      lymphogenesis was clearly observed, especially in patients with tumors invading
      the anastomosis site of Billroth-II reconstruction. Station Nos. 110 (lower
      paraesophageal) and 111 (supradiaphragmatic) lymph nodes were also stained,
      despite being considered sites of distant metastasis irrespective of the method
      of reconstruction. CONCLUSIONS: On the basis of the evidence of altered lymphatic
      flow and the incidence of lymph node metastases in remnant stomach cancer, left
      upper abdominal evisceration with para-aortic lymph node dissection should be
      performed in advanced remnant stomach cancer.

PMID- 11995503
TI  - Sepsis delays gastric emptying following pylorus-preserving
      pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: The mechanism of delayed gastric emptying following pylorus
      preserving pancreaticoduodenectomy is not completely understood. METHODOLOGY: The
      records of 25 patients who underwent pylorus-preserving pancreaticoduodenectomy
      were reviewed. Correlations of postoperative delayed gastric emptying defined as
      the need for postoperative nasogastric decompression for > 10 days, with
      perioperative parameters and clinical outcome were analyzed. RESULTS: Delayed
      gastric emptying occurred in 13 patients. Age, gender, presence of pancreatic
      carcinoma, operating time, estimated blood loss, and preservation of right
      gastric artery did not affect the incidence of delayed gastric emptying. Patients
      with pancreatic fibrosis (n = 13) had a significantly lower incidence of delayed
      gastric emptying than in those without fibrosis (n = 12) (23% vs. 83%, P =
      0.0048). Ten patients developed postoperative septic complications, including
      anastomotic leakage (n = 7), pneumonia (n = 2), and severe wound infection (n =
      1). The incidence of postoperative delayed gastric emptying was significantly
      higher in patients with septic complications than in those without septic
      complications (100% vs. 20%, P = 0.0001). Also, patients with intraabdominal
      sepsis had a significantly higher incidence of delayed gastric emptying (P =
      0.0052). CONCLUSIONS: Delayed gastric emptying following pylorus-preserving
      pancreaticoduodenectomy is related to the presence of non-fibrotic pancreas and
      postoperative septic complications.

PMID- 11995504
TI  - A multiple logistic regression analysis of risk factors in different subtypes of
      gastric ulcer.
AB  - BACKGROUND/AIMS: To elucidate the relationship among disparate ulcer risk factors
      in 3 subtypes of gastric ulcer. METHODOLOGY: One hundred and fifty-nine age
      matched controls, 30 patients with ulcer craters in the gastric body (GU-I), 55
      with coexistent gastroduodenal ulcer (GU-II), and 69 with ulcer craters in the
      prepyloric region (GU-III) were examined for potential risk factors. These
      included cigarette smoking, nonsteroidal anti-inflammatory drug use, Helicobacter
      pylori infection, gender and ABO blood group. Using multiple logistic regression
      analysis, Odds ratios of relevant risk factors associated with different subtypes
      of gastric ulcer were reported. RESULTS: Among all gastric ulcer subsets,
      cigarette smoking, nonsteroidal anti-inflammatory drugs use and H. pylori
      infection were independent ulcer risk factors. For GU-I, smoking (OR: 3.98; 95%
      CI: 1.44-11.0) and nonsteroidal anti-inflammatory drugs use (OR: 4.33; 95% CI:
      1.10-17.1) raised the likelihood of ulceration. For GU-II and GU-III, smoking,
      nonsteroidal anti-inflammatory drug use and H. pylori infection were identified
      as risk factors. H. pylori infection carried the strongest association with
      gastroduodenal ulcer (OR: 9.29; 95% CI: 3.11-27.7) in GU-II, and nonsteroidal
      anti-inflammatory drug use generated the highest possibility of GU-III (OR: 11.3;
      95% CI: 3.49-36.5). Nonsteroidal anti-inflammatory drug use also markedly raised
      the likelihood of multiple gastric ulcers (OR: 17.0; 95% CI: 4.21-68.9).
      CONCLUSIONS: Stratification analysis showed differential influences of risk
      factors on separate subtypes of gastric ulcer. These data support the hypothesis
      that peptic ulcer disease is heterogeneous in etiology and pathogenesis.

PMID- 11995505
TI  - You have a voice in nursing's preferred future ... from a national perspective.

PMID- 11995506
TI  - The Florida Nurse Practice Act. The myths and the realities.

PMID- 11995507
TI  - Blended role advanced practice in gerontological nursing.

PMID- 11995508
TI  - The Bioethics Focus Group report.

PMID- 11995509
TI  - New child health insurance: Florida KidCare.

PMID- 11995510
TI  - An exemplar for clinical expertise in obstetrics.

PMID- 11995513
TI  - Baptist Hospital of Miami named "Magnet Hospital" for excellence in nursing
      services.

PMID- 11995511
TI  - The nursing shortage ... will we become an endangered species or near extinction
      in the new millennium.
AB  - In conclusion, it is obvious to each of us that the nursing shortage issue is
      complex. There are no simple solutions. In the acute care arena we can expect to
      see the usual recruitment wars using sign-on bonuses, increased salaries for per
      diem staff, internship programs and all sorts of methods used in the past to
      recruit needed staff. It is that sort of crisis management and short term
      thinking that has plagued the profession in the past. These are bandaid efforts
      especially in light of the factors of supply vs demand with short-term quick
      fixes. There must be, however, more efforts towards addressing the long-term
      issues such as wage compression, differentiated practice and pay, effective
      models of care delivery, educating the public about nursing, and
      public/government funding more nursing education and research at all levels.
      There may need to be a federal subsidy for nursing education and recruitment
      included to affect the magnitude of this potential societal problem. The
      profession is at a crossroads. One thing is certain however, this nursing
      shortage is different and will get worse before it gets better. Let's not let the
      demand for nurses become so large and supply become so small that we are an
      endangered species or near extinction in the new millennium. What will be the
      scenario for nurses in 2050? Are we, as the largest healthcare profession, so
      complacent about our continued existence that we are at a point of paralysis? Are
      we in such a state of deep depression in response to current changing environment
      that we will allow ourselves to be devoured by our predators. Are we
      cannibalistic as we eat our young and chew on our own unresolved internal issues
      with a lack of action? Are we septic as a result of our own self-inflicted
      professional wounds? Our profession must become immediately aware of our possibly
      tenuous future. We must work together as a community of nurses to strategically
      address the areas of recruitment, education, retention and environmental factors
      with actionable plans for short term and long term solutions. There is ample
      opportunity to redefine and build new paradigms and implement structures that
      will enhance and encourage the growth of the profession into the new millennium.
      Your Florida nursing professional associations, leaders, and educators are
      working towards solutions and invite you to help shape the future of nursing by
      participating actively in your professional organizations.

PMID- 11995514
TI  - The transition from student to professional nurse.

PMID- 11995515
TI  - A nursing student's checklist for solving problems.

PMID- 11995516
TI  - Defending your license--a complex problem.

PMID- 11995517
TI  - Highlights from the Clinical Excellence Conference.

PMID- 11995518
TI  - Workers compensation.

PMID- 11995520
TI  - Empowering nursing students to become leaders in the profession.

PMID- 11995521
TI  - The relationship between miscommunication and medical malpractice.

PMID- 11995522
TI  - Nurses as drug dealers? Organized medicine: get real!

PMID- 11995523
TI  - American with Disabilities Act.

PMID- 11995524
TI  - Excerpts from the clinical excellence conference.

PMID- 11995525
TI  - Family Medical Leave Act.

PMID- 11995526
TI  - "Why not go out on a limb? Isn't that where the fruit is?".

PMID- 11995527
TI  - Membership recruitment and retention: strengthening the link with students.

PMID- 11995528
TI  - A model for school health programs.

PMID- 11995530
TI  - Litigation risks in intravenous therapy.

PMID- 11995531
TI  - Nursing informatics: a universal nursing language.
AB  - Knowledge is necessary to use information to make decisions in nursing
      situations. Nursing data must be grouped in a logical way so the
      interrelationship between the classification systems and specific concrete
      phenomena in individual nursing situations is useful. The processing and
      management of information for decision making is the focus in nursing and health
      care. The development and use of language that represents the domain of nursing
      is an essential dimension in an integrated and coordinated health care delivery
      system. The design and acceptance of a universal nursing language system is
      critical to collect appropriate data to document nursing's role, functions, and
      effectiveness in health care by the year 2000. This is an urgent message for
      nurses to be involved in the technology and nursing care documentation to
      demonstrate quality care that is cost effective. In the next century, nurses must
      speak a common nursing language that has the same meaning for all nurses.

PMID- 11995532
TI  - Workplace issues.

PMID- 11995533
TI  - Nursing science can help frail elders at risk in Florida.

PMID- 11995534
TI  - North Carolina Nurses Association. Position statement on nursing education.

PMID- 11995535
TI  - North Carolina Nurses Association. Position statement on advanced practice by
      certified specialists in psychiatric and mental health nursing.

PMID- 11995537
TI  - Council of psychiatric and mental health nurses in advanced practice.

PMID- 11995538
TI  - Council on continuing education & staff development conducts statewide survey.

PMID- 11995539
TI  - Who speaks for healthcare?

PMID- 11995540
TI  - Profile of nurse practitioner alumni: UNC-Chapel Hill, 1970-1990.

PMID- 11995541
TI  - North Carolina names "Search for Excellence" winner.

PMID- 11995542
TI  - Health policy and nursing: a political connection.

PMID- 11995543
TI  - The caregiver at risk.

PMID- 11995545
TI  - There's no such thing as "just a med/surg nurse".

PMID- 11995544
TI  - Press conferences herald health care legislation.

PMID- 11995546
TI  - Peer review for nurses: a model to ensure professional accountability.

PMID- 11995547
TI  - What are the legal implications of accepting a physician's orders indirectly from
      one of the physician's employees?

PMID- 11995548
TI  - NCNA launches statewide health project.

PMID- 11995549
TI  - Project 6,000: a weight reduction program.

PMID- 11995551
TI  - 1998 Medicare changes: facts, fallacies and fiction.

PMID- 11995550
TI  - When a student refuses to care for a patient, what action should the faculty
      member take?

PMID- 11995552
TI  - Domestic violence takes a toll on families and the workplace.

PMID- 11995553
TI  - Children's health insurance a reality.

PMID- 11995554
TI  - A profile of newly licensed registered nurses in North Carolina: 1997.

PMID- 11995555
TI  - Managed care: nursing's blueprint for action.

PMID- 11995556
TI  - Incivility, aggression and violence directed toward nurses outside the hospital
      emergency department.

PMID- 11995558
TI  - Title of legislation: occupational Safety and Health Act (OSHA).

PMID- 11995557
TI  - From one nurse to another.

PMID- 11995559
TI  - New ways to return to school.

PMID- 11995560
TI  - Men in nursing: the novelty is gone.

PMID- 11995561
TI  - National attitudes of young people towards sex, health and AIDS.

PMID- 11995562
TI  - Washington conference on integrated patient care.

PMID- 11995563
TI  - HCFA issues program memorandum.

PMID- 11995564
TI  - New licensure proposals.

PMID- 11995565
TI  - Teaching nursing students--cure for burn-out.

PMID- 11995566
TI  - NC Accreditation Commission expands accreditation to in-home nursing services.

PMID- 11995568
TI  - Pew Commission update.

PMID- 11995567
TI  - Council of Nurse Educators hold successful program on collaboration between
      education and practice.

PMID- 11995569
TI  - Environmental tobacco smoke.
AB  - A healthy and safe environment is a national public health priority. Clean air,
      free from tobacco smoke, is particularly vital since researchers have documented
      the link between tobacco smoke and increased morbidity and mortality in both
      smokers and non-smokers. Specifically, target goals for the year 2000, as
      established in the document, Health People 2000 (National Center for Health
      Statistics, 1990, 1994), include increasing the proportion of schools that are
      tobacco-free to 100%, increasing the proportion of work sites with formal smoking
      policies to 75%, and increasing the number of states with clean indoor air laws
      to 50%. As part of their role in promoting the public health and welfare, nurses
      need to actively support and help implement smoking policies in public places.

PMID- 11995570
TI  - NC Center for Nursing prepares report on nursing workforce trends.

PMID- 11995571
TI  - Governor's Commission on Uninsured Children.

PMID- 11995572
TI  - Proposed Blue Cross/Blue Shield conversion still controversial.

PMID- 11995573
TI  - Thoughts on chemical dependency.

PMID- 11995574
TI  - Reimbursement notification error made by Blue Cross/Blue Shield.

PMID- 11995575
TI  - Reimbursement for nurses becomes a reality.

PMID- 11995576
TI  - Why differentiated entry level practice?

PMID- 11995577
TI  - Membership survey results are in.

PMID- 11995578
TI  - Research activity and utilization in North Carolina nursing service
      organizations.

PMID- 11995579
TI  - I went to Zambia to teach.

PMID- 11995580
TI  - North Carolina immunization laws for children and college students; the latest
      update.

PMID- 11995581
TI  - Nurses providing access to health care.

PMID- 11995583
TI  - Off the sidelines: nursing's role in health care reform.

PMID- 11995584
TI  - Commission for health services schedules public hearings.

PMID- 11995585
TI  - Position statement on HIV testing.

PMID- 11995586
TI  - American Nurses Association and North Carolina Nurses Association. Statement on
      drug testing for health care workers.

PMID- 11995587
TI  - Teen Pregnancy Prevention Week.

PMID- 11995588
TI  - Nurse terminated for three med. errors in two years.

PMID- 11995589
TI  - Arbitrator orders nurse reinstated: hospital appeals. Case on point: Boston Med.
      Ctr. v. Service Employees Int. Union, 2001 WL 881257 F.3d-MA.

PMID- 11995590
TI  - OH: nurses fail to follow orders re Coumadin: complications follow--patient's
      death results.

PMID- 11995591
TI  - TX: agency 'temp' OR nurse injured in OR: workers' comp. no bar to suit v.
      hospital or Dr.

PMID- 11995592
TI  - Sexual assault of semi-comatose quadriplegic in nursing home. Case on point:
      Regions Bank & Trust v. Stone Co. Skilled Nursing Facility, 2001 WL 766965-AR.

PMID- 11995593
TI  - Women's trials: the approval of the first oral contraceptive pill in the United
      States and Great Britain.

PMID- 11995595
TI  - Disease and its impact on politics, diplomacy, and the military: the case of
      smallpox and the Manchus (1613-1795).

PMID- 11995594
TI  - Why did Humphry Davy and associates not pursue the pain-alleviating effects of
      nitrous oxide?

PMID- 11995596
TI  - The marvellous network and the history of enquiry into its function.

PMID- 11995597
TI  - Physical therapy for vulvar vestibulitis syndrome: a retrospective study.
AB  - This retrospective study evaluated the effectiveness of physical therapy in
      relieving painful intercourse and improving sexual function in women diagnosed
      with vulvar vestibulitis. This syndrome is a frequent cause of premenopausal
      dyspareunia and is characterized by a sharp, burning pain located within and
      limited to the vulvar vestibule (vaginal entry) and elicited primarily via
      pressure applied to the area. Participants were 35 women with vulvar vestibulitis
      who took part in physical therapy treatment for an average of 7 sessions. We
      conducted telephone interviews to assess whether physical therapy or other
      subsequent treatments impacted on pain during intercourse and sexual functioning.
      Length of treatment follow up ranged from 2 to 44 months, with a mean of 16
      months. Physical therapy yielded a complete or great improvement for 51.4% of
      participants, a moderate improvement for 20.0% of participants, and little to no
      improvement for the other 28.6%. Treatment resulted in a significant decrease in
      pain experienced both during intercourse and gynecological examinations; it also
      resulted in a significant increase in intercourse frequency and levels of sexual
      desire and arousal. Successful patients were significantly less educated than
      nonsuccessful patients. Findings demonstrate that physical therapy is a promising
      treatment modality for dyspareunia associated with vulvar vestibulitis.

PMID- 11995598
TI  - The significance of heavy pornography involvement for romantic partners: research
      and clinical implications.
AB  - This article presents a paradigm case portrait of female romantic partners of
      heavy pornography users. Based on a sample of 100 personal letters, this portrait
      focuses on their often traumatic discovery of the pornography usage and the
      significance they attach to this usage for (a) their relationships, (b) their own
      worth and desirability, and (c) the character of their partners. Finally, we
      provide a number of therapeutic recommendations for helping these women to think
      and act more effectively in their very difficult circumstances.

PMID- 11995599
TI  - Case report: the management of bone demineralization associated with long-term
      treatment of multiple paraphilias with long-acting LHRH agonists.
AB  - A patient with multiple paraphilias had been successfully treated for 10 years
      with a long-acting LHRH agonist with complete suppression of deviant sexual
      activity. However, during treatment, he demonstrated bone demineralization, as
      documented by serial bone densitometry studies. A treatment regimen was
      instituted, which resulted in the cessation or partial reversal of bone loss.

PMID- 11995600
TI  - Age as a differential characteristic of rapists, pedophiles, and sexual sadists.
AB  - In this study, we investigated the role of age in three categories of 168 sex
      offenders, including 53 rapists, 62 pedophiles, and 53 sadists. On the basis of
      the match between requisites of completing each type of sexual offense, we
      hypothesized that rapists would be less represented in the older age group,
      whereas pedophilic and sexually sadistic offenders would show a more muted
      decline with age. This hypothesis was supported by the data, clearly a showing
      smaller number of rapists in the over 40 group relative to the number of
      pedophiles and sadists (p = 0.0009.) Further examination of the files eliminated
      the alternate explanation ascribing this pattern to lack of opportunity in older
      rapists because of incarceration. These results suggest that age over 40 may
      mitigate incidence of recidivism in rapists, but not in pedophiles or sexual
      sadists. Approximately one third of the sexual sadists had committed either first
      or second-degree murder, whereas none of the nonsadistic rapists or pedophiles
      had these crimes on their records. The data further justify categorization of sex
      offenders into nonsadistic rapist, sadistic rapist, and pedophilic offenders in
      future research to enhance precision in delineating demographic characteristics
      and putative causal explanations for sexual offending.

PMID- 11995601
TI  - Books helpful to patients with sexual and marital problems.
AB  - Providing patients with helpful and timely resource materials requires clinicians
      to be familiar with an ever-changing and over-whelmingly large body of
      information. To assist clinicians in the task of assembling current useful
      materials, we surveyed members of the Society for Sex Therapy and Research by
      mail and an electronic listserve. The survey forms requested respondents to list
      books, videotapes, and Internet sites that they recommended to their patients
      with specific sexual/marital problems. Fifty-two of 216 surveys were returned for
      a response rate of 24%. Responses were included if they were cited at least three
      times. Each citation was verified for accuracy and developed into an acceptable
      journal-quality reference. Frequency counts for responses were calculated, and a
      bibliography was developed.

PMID- 11995602
TI  - Sexuality and marital life: results of a survey.
AB  - This article presents the results of a telephone survey regarding the conjugal
      and sex life of men and women from the Montreal region. Surprising as it may
      seem, the relationship between sexual and marital functioning within the couple
      has been the focus of little study to date. In fact, relatively little is known
      about the relationship among sexual behavior, sexual attitudes, sexual fantasies,
      and marital functioning. In this survey, a questionnaire covering these four
      variables was administered to 996 subjects chosen at random. The results indicate
      that women seem to have a more positive perception of their sexual behavior,
      whereas men seem to have a more positive perception of their marital life.
      Multiple regression analyses were run to examine the relationship between marital
      functioning and items related to sexual functioning. The links between sexual
      satisfaction and other items of the questionnaire concerning sexual behavior,
      sexual attitudes, and sexual fantasies were also analyzed. For this purpose, we
      subdivided the subjects into two age groups (under 60 and 60 and over) based on
      the loss of interest in sexual activity that the questionnaire allowed to discern
      in the 60+ group. The relationship between marital functioning and items related
      to sexual behavior proved statistically significant. Various items pertaining to
      sexual functioning also proved to be related to a global assessment of sexual
      satisfaction. Cognitive variables (sexual attitudes and sexual fantasies) were
      found to influence sexual satisfaction but had a lesser impact on marital
      functioning. Gender and age (under 60 or 60 and over) also had an effect on these
      relationships.

PMID- 11995603
TI  - Postorgasmic illness syndrome: two cases.
AB  - We describe the symptoms of a postejaculatory syndrome in two men with
      spontaneous ejaculations. The syndrome consists of severe fatigue, intense
      warmth, and a flulike state, with generalized myalgia. These symptoms occur
      rapidly after ejaculation and only disappear after 4 to 7 days. The symptoms are
      so severe that sexual activity is avoided. The cluster of symptoms is named
      postorgasmic illness syndrome (POIS). To date, no explanation has been offered
      for the etiology and pathogenesis of the symptoms, and the prevalence is unknown.
      Both cases are presented to draw attention to this syndrome for further research
      regarding etiology, pathogenesis, and treatment.

PMID- 11995604
TI  - Perceptions of own sexual lies influenced by characteristics of liar, sex
      partner, and lie itself.
AB  - The current study examined perceptions of own sexual lies (lies to sex partners
      about sexual matters), in particular the perceived acceptability and seriousness
      of such lies, as well as potential determinants of such perceptions. Participants
      were 166 undergraduates who were asked to recall a recent event in which he or
      she had engaged in sexual lying and then respond to several questions regarding
      the event. Results showed that those who recalled relatively risk-relevant and
      self-protective sexual lies saw their lies as more serious and less acceptable.
      Moreover, those who told relatively risk-irrelevant and other-protective sexual
      lies reported less history of sexual lying or infidelity and more liking for the
      lie recipient in the event. These findings have implications both for safer-sex
      interventions and for interventions in intimate relationships.

PMID- 11995605
TI  - Evaluation of sex- and gender-assignment decisions in patients with physical
      intersex conditions: a methodological and statistical note.

PMID- 11995606
TI  - Urethral and pelvic floor continence factors. The Fourth Biennial Symposium on
      Lower Urinary Tract Physiology and Pathophysiology. November 19-20, 1999.
      Holmenkollen Park Hotel, Oslo Norway.

PMID- 11995607
TI  - Dynamics of intracellular organelles and molecular machines. Proceedings of the
      11th Winternational Symposium of the Canadian Society of Biochemistry and
      Molecular & Cellular Biology. Chateau Mont Sainte-Anne Beaupre, Quebec, Canada.
      February 8-11, 2001.

PMID- 11995608
TI  - Proceedings from the Fourth Japanese Clinicopathological Conference on Renal
      Allograft Pathology. Tokyo, Japan. July 8, 2000.

PMID- 11995609
TI  - Clinical teaching is the key to improved practice.

PMID- 11995610
TI  - AmBisone: an international workshop. Australia. July 8-9, 2000.

PMID- 11995612
TI  - ACOG committee opinion. Medical futility.

PMID- 11995611
TI  - Hypothermia associated with autonomic dysreflexia after traumatic spinal cord
      injury.
AB  - Individuals with traumatic upper thoracic and cervical spinal cord injuries are
      at increased risk for the development of both thermoregulatory dysfunction and
      autonomic dysreflexia. It is unclear, however, what effect reflex autonomic
      sympathetic outflow has on thermoregulatory dysfunction during episodes of
      autonomic dysreflexia. The following case of an individual with C5 tetraplegia
      and both thermoregulatory dysfunction and autonomic dysreflexia illustrates the
      profound effects that the autonomic nervous system may have on body temperature
      in individuals at risk for this complication.

PMID- 11995613
TI  - ACOG committee opinion. Risk of breast cancer with estrogen-progestin replacement
      therapy.
AB  - Recent articles have examined the association between the use of combination
      estrogen-progestin regimens for hormone replacement therapy (HRT) and the risk of
      breast cancer. The objective of this Committee Opinion is to evaluate critically
      the presented evidence. Although epidemiologic studies suggest that the addition
      of progestins to estrogens may increase the risk of breast cancer, this increased
      risk has not been proved. The American College of Obstetricians and Gynecologists
      continues to recommend that HRT be considered as a treatment to relieve vasomotor
      symptoms and genitourinary tract atrophy and to reduce the risk of osteoporosis
      and, potentially, cardiovascular disease. Postmenopausal women should be apprised
      of the current understanding of the risks and benefits of HRT. When considering
      the use of HRT for longer than 5 years, the clinician and individual patient
      should weigh the benefits versus the potential side effects and risks for that
      particular patient.

PMID- 11995614
TI  - ACOG committee opinion. Von Willebrand's disease in gynecologic practice.
AB  - Von Willebrand's disease is one of the most common inherited bleeding disorders.
      Inherited and acquired disorders of coagulation and hemostasis should be
      considered in the differential diagnosis of menorrhagia and abnormal uterine
      bleeding. This Committee Opinion provides screening recommendations for von
      Willebrand's disease and describes treatment options.

PMID- 11995615
TI  - ACOG committee opinion. Air travel during pregnancy.
AB  - In the absence of obstetric or medical complications, pregnant women can observe
      the same general precautions for air travel as the general population and can fly
      safely up to 36 weeks of gestation. In-craft environmental conditions, such as
      low cabin humidity and changes in cabin pressure, coupled with the physiologic
      changes of pregnancy, do result in maternal adaptations, which could have
      transient effects on the fetus. Pregnant air travelers with medical problems that
      may be exacerbated by a hypoxic environment, but who must travel by air, should
      be prescribed supplemental oxygen during air travel. Pregnant women at
      significant risk for preterm labor or with placental abnormalities should avoid
      air travel. Because air turbulence cannot be predicted and the risk for trauma is
      significant, pregnant women should be instructed to continuously use their seat
      belts while seated, as should all air travelers. Pregnant air travelers may take
      precautions to ease in-flight discomfort, and although no hard evidence exists,
      preventive measures can be employed to minimize risks.

PMID- 11995616
TI  - Pay for performance promoted in California.
AB  - The California-based Integrative Healthcare Association (IHA), a collaborative
      group made up of health plans, physician groups, employers, consumers, and health
      care systems, last month unveiled a new initiative--called Pay for Performance-
      that would base physician payments on providing quality care each year and would
      give consumers comparative data on physician groups.

PMID- 11995617
TI  - It's the taking part that counts.

PMID- 11995618
TI  - The sanity clause and the lay representative.

PMID- 11995619
TI  - Is it wrong to go out with my patient?

PMID- 11995620
TI  - How do I handle claims of cruelty?

PMID- 11995621
TI  - More than just drips, drains and dressings.

PMID- 11995622
TI  - Using hyperbaric oxygen to treat a diabetic foot lesion.

PMID- 11995623
TI  - Nurses are the key to ending A&E chaos.

PMID- 11995624
TI  - Carrying out a clinical audit.

PMID- 11995625
TI  - Pemphigus as a model of organ-specific humoral autoimmune disease. Abstracts of
      the National Pemphigus Foundation and the American Autoimmune Related Disease
      Association International Meeting. April 20-21, 2001. Bethesda, MD, USA.

PMID- 11995626
TI  - [Abstracts from the 3rd Novo Nordisk Meeting of Internists of Endocrinology,
      Diabetes, Metabolism. 29 November-1 December 2001].

PMID- 11995627
TI  - Trace element speciation in biological and environmental sciences. Second
      International Conference on Trace Element Speciation in Biomedical, Nutritional
      and Environmental Sciences. Neuherberg, Germany. May 7-11, 2001.

PMID- 11995628
TI  - Student participation assessment tool.

PMID- 11995629
TI  - Drugs elevating extracellular adenosine promote regeneration of haematopoietic
      progenitor cells in severely myelosuppressed mice: their comparison and joint
      effects with the granulocyte colony-stimulating factor.
AB  - We tested capabilities of drugs elevating extracellular adenosine and of
      granulocyte colony-stimulating factor (G-CSF) given alone or in combination to
      modulate regeneration from severe myelosuppression resulting from combined
      exposure of mice to ionizing radiation and carboplatin. Elevation of
      extracellular adenosine was induced by joint administration of dipyridamole (DP),
      a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate
      (AMP), serving as an adenosine prodrug. DP+AMP, G-CSF or all these drugs in
      combination were administered in a 4-d treatment regimen starting on day 3 after
      induction of myelosuppression. Comparable enhancements of haematopoietic
      regeneration due to elevation of extracellular adenosine or to action of G-CSF
      were demonstrated as shown by elevated numbers of haematopoietic progenitor cells
      for granulocytes/macrophages (GM-CFC) and erythrocytes (BFU-E) in the bone marrow
      and spleen in early time intervals after termination of the drug treatment, i.e.
      on days 7 and 10 after induction of myelosuppression. Coadministration of all the
      drugs further potentiated the restoration of progenitor cell pools in the
      haematopoietic organs. The effects of the drug treatments on progenitor cells
      were reflected in the peripheral blood in later time intervals of days 15 and 20
      after induction of myelosuppression, especially as significantly elevated numbers
      of granulocytes and less pronounced elevation of lymphocytes and erythrocytes.
      The results substantiate the potential of drugs elevating extracellular adenosine
      for clinical utilization in myelosuppressive states, e.g. those accompanying
      oncological radio- and chemotherapy.

PMID- 11995630
TI  - Dietary behaviors associated with total fat and saturated fat intake.
AB  - OBJECTIVE: To estimate percentages of US adults who have adopted behaviors
      promoted by dietary guidance about how to reduce fat intake, and to assess
      relationships between these behaviors and intake of energy from total and
      saturated fat. DESIGN: Relationships were examined between intake of total and
      saturated fat from two 24-hour recalls in the US Department of Agriculture's 1994
      1996 Continuing Survey of Food Intakes by Individuals and responses to 19 fat
      related behavior questions on the follow-up Diet and Health Knowledge Survey
      (DHKS). SUBJECTS: Data are from a national sample of 5,649 individuals 20 years
      of age and older. STATISTICAL ANALYSES PERFORMED: Multiple regression models are
      used to identify dietary behaviors, demographic factors, and personal
      characteristics that are determinants of fat intake. RESULTS: In this study, the
      percentage of US adults who consistently followed the low-fat behaviors ranged
      from 8% to 70%. The most highly adopted behaviors (45% or more of adults)
      included trimming fat from meat, removing skin from chicken, and eating chips
      infrequently. The least highly adopted behaviors (15% or less of adults) included
      eating baked or boiled potatoes without added fat, avoiding butter or margarine
      on breads, eating low-fat instead of regular cheeses, and having fruit for
      dessert when dessert is eaten. Together, the 19 fat-related behavior questions on
      the DHKS formed a statistically significant predictor for total fat and saturated
      fat intake, expressed as a percent of energy (P<.0001). Key behaviors in terms of
      their predicted effect on lowering both total and saturated fat intake were never
      adding fat to baked or boiled potatoes, not eating red meats, eating less than 3
      eggs per week, and never eating chicken fried. Predicted effects of these key
      behaviors in terms of lowering fat intake as a percentage of energy were > or =
      1.5 percentage points for total fat and > or = 0.5 percentage point for saturated
      fat. CONCLUSIONS: Results have applications for designing brief fat assessment
      instruments and for identifying key nutrition education messages that promote
      important fat-lowering behaviors.

PMID- 11995631
TI  - Environmental factors influencing public health and medicine: policy
      implications.
AB  - Environmental health threats are increasing throughout the United States,
      particularly in low-income populations and in communities of color. Environmental
      science researchers are investigating plausible associations between the
      environment and human health. As a result, the role and responsibility of the
      primary care physicians and other health care providers are changing. This paper
      highlights selected lines of evidence suggesting that clinicians should now
      consider interactions between humans and their environment as central to
      providing effective primary care. Subject areas include: exposure to
      environmental agents, reproductive toxicity, pulmonary disease, neurobehavioral
      toxicity, endocrine disruptors, mechanisms of environmental disease, and cultural
      competence. Concerns about these and other environmentally related issues
      influence the manner in which primary care is practiced now, and will be
      practiced in the future. Biomedical technology and community awareness demand
      that physicians pay more attention to advances in environmental medicine.
      Ironically, one of the least taught subjects in medical school is environmental
      medicine. To effectively respond to growing concerns about the role of the
      environment in human health, clinicians, researchers, educators, public policy
      officials, and the general public must join together to reduce the risk of
      environmental health threats and improve quality of life.

PMID- 11995632
TI  - Reduced prevalence of atrial fibrillation in black patients compared with white
      patients attending an urban hospital: an electrocardiographic study.
AB  - Electrocardiographic differences occur between African-American and white
      persons. The cardiac rhythms of 2123 African-American and white hospital patients
      from 20 through 99 years of age were studied in a consecutive manner. The
      prevalence of atrial fibrillation increases dramatically with advancing age in
      both African-American and white patients. The prevalence of atrial fibrillation
      begins to increase at age 60 years and continues to increase through the 10th
      decade of life, although the rate of rise of the prevalence of atrial
      fibrillation is less in African-American patients compared with white patients.
      The cause of the reduced prevalence of atrial fibrillation in African-American
      patients remains unexplained. Atrial fibrillation occurs in 2.5% of African
      American patients compared with 7.8% of white patients attending an urban
      hospital. There is little difference in the prevalence of atrial fibrillation
      between men and women. Atrial fibrillation occurs nearly seven times more often
      than does atrial flutter.

PMID- 11995633
TI  - Macrophages, chemokines and neuronal injury in HIV-1-associated dementia.
AB  - Human immunodeficiency virus type-one (HIV- 1)-associated dementia (HAD) is
      manifested as a spectrum of behavioral, motor and cognitive dysfunctions. The
      disorder commonly occurs during late stage HIV disease and remains an important
      complication despite highly active antiretroviral therapies. A metabolic
      encephalopathy, fueled by neurotoxic secretions from brain mononuclear phagocytes
      (MP) (macrophages and microglia) underlies HIV- I neuropathogenesis. One pivotal
      question, however, is how brain MP evolve from neurotrophic to neurotoxic cells.
      The interplay between the virus, the macrophage and the neuron has just recently
      begun to be unraveled. Along with a multitude of other MP secretory products,
      chemokines effect neuronal function by engaging neuronal receptors then
      activating pathways that alter synaptic transmission, cell growth, injury and
      protection. Both neurons and glia secrete chemokines. Interestingly, HIV-1 and
      its gene products can mimic chemokine neuronal signaling by binding to neuronal
      chemokine receptors or by other non-specific mechanisms. The elucidation of
      mechanisms involved in chemokine-mediated neural compromise will likely provide
      unique insights into the pathogenesis and treatment, not only of HAD, but of a
      wide range of neurodegenerative disorders.

PMID- 11995634
TI  - A perturbative calculation of the rovibrational energy levels of methane.
AB  - The rovibrational energy levels of methane are determined from a quartic ab
      initio potential energy force field where the expansion coordinates are the Morse
      coordinates for the stretches and extension coordinates for the bends. Energies
      are calculated using canonical Van Vleck perturbation theory. Results are
      obtained for both rotation-vibration Hamiltonians expressed as functions of
      curvilinear and rectilinear normal coordinates. Second, fourth, and sixth order
      curvilinear results are compared with experimental results, and fourth order
      results for the rectilinear and curvilinear Hamiltonian are compared to each
      other. The calculated rovibrational levels are in good agreement with the
      experimental values for low J levels. The calculated rotational level splittings
      are in even better agreement with the experiment. In particular, the ground state
      tetrahedral splittings, which are as small as 10(-4) cm(-1), are well reproduced
      by our calculations at sixth order.

PMID- 11995636
TI  - The effects of reverse atrial electrical remodeling on atrial defibrillation
      thresholds.
AB  - The implantable atrial defibrillator is a developing therapeutic option for
      paroxysmal atrial fibrillation, but shock related discomfort continues to be a
      limiting factor. To further characterize successful defibrillation, the
      relationship between reverse atrial electrical remodeling and internal atrial
      defibrillation thresholds in canines with chronic atrial fibrillation was
      examined. Testing was performed in 21 dogs. Chronic atrial fibrillation was
      induced in eight dogs by creating moderate mitral regurgitation and rapidly
      pacing the right atrium for > or = 6 weeks. The atrial fibrillation cycle length,
      atrial effective refractory period, refractory period dispersion, and internal
      atrial defibrillation thresholds were determined after establishment of chronic
      atrial fibrillation after 4 hours of sinus rhythm postcardioversion and 7 days of
      sinus rhythm postcardioversion. These measurements were then compared to a normal
      population of 13 dogs. The atrial defibrillation thresholds were 6.6 J (1.9-10.1
      J) initially, 2.9 J (1.5-3.7 J) after 4 hours of sinus rhythm, and 0.9 J (0.4-1.3
      J) after 7 days of sinus rhythm (P = 0.04). This decrease was associated
      inversely with the atrial effective refractory period (P < 0.03), and atrial
      fibrillation cycle length (P < 0.05), and with a decrease in atrial refractory
      period dispersion after 7 days of sinus rhythm (P = 0.04). These
      electrophysiological measurements reached normal population levels by 7 days.
      Atrial defibrillation thresholds decrease as atrial reverse electrical remodeling
      occurs and this reduction corresponds to increased atrial fibrillation cycle
      length, increased atrial refractoriness, and decreased refractory period
      dispersion.

PMID- 11995635
TI  - In vitro studies on a bioreactor module containing encapsulated goat hepatocytes
      for the development of bioartificial liver.
AB  - BACKGROUND: A bioartificial liver may act as a temporary metabolic bridge in
      patients with acute liver failure. We devised a bioreactor module containing
      encapsulated goat hepatocytes and studied its efficiency in detoxifying ammonia.
      METHODS: A hollow-glass bioreactor module was designed and fabricated locally.
      The module was inoculated with alginate poly-L-lysine microcapsules with
      entrapped goat hepatocytes. Metabolism of ammonia and glucose was assessed.
      Antibody-mediated cell cytotoxicity was also assessed. RESULTS: The optimum
      encapsulated goat hepatocyte concentration was 12-18 billion at a perfusate flow
      rate of 30 mL/min under oxygenated condition. The optimum ammonium chloride
      concentration for detoxification was 2.5-5.0 mM. There was little or no cytolysis
      of encapsulated hepatocytes on exposure to complement-inactivated human AB serum.
      CONCLUSION: Encapsulated goat hepatocytes efficiently detoxified ammonia to urea.
      Cells were metabolically active up to 48 hours, indicating their feasibility for
      use in a bioreactor module. Encapsulation protected the hepatocytes from antibody
      mediated cell lysis.

PMID- 11995637
TI  - Quantifying psychiatric comorbidity--lessions from chronic disease epidemiology.
AB  - BACKGROUND: Comorbidity research in psychiatric epidemiology mostly uses measures
      of association like odds or risk ratios to express how strongly disorders are
      linked. In contrast, chronic disease epidemiologists increasingly use measures of
      clustering, like multimorbidity (cluster) coefficients, to study comorbidity.
      This article compares measures of association and clustering. METHODS: Narrative
      review, algebraical examples, a secondary analysis of an existing dataset and a
      pooled analysis of published data. RESULTS: Odds and risk ratios, but the former
      more than the latter, confound clustering with coincidental comorbidity.
      Multimorbidity coefficients provide a pure estimate of clustering which is the
      proportion of the association between disorders that is of etiological interest.
      Odds and risk ratios can express comorbidity between no more than two disorders,
      whilst clustering coefficients, although computationally laboursome, can capture
      multimorbidity of any number of disorders. Cluster coefficients depend less on
      the prevalence of illness in study groups than measures of association.
      CONCLUSION: Odds and risk ratios are well suited for comorbidity research which
      focuses on which sets of disorders or syndromes tend to occur in combination and
      the implications of this for, for instance, nosological classification, a
      traditional interest of psychiatric epidemiology. However, the cluster
      coefficient is to be preferred if the interest is more aetiological, addressing
      for example why certain individuals are prone to multiple health problems.

PMID- 11995638
TI  - Morphological effects on the hard palatine mucosa of Calomys callosus submitted
      to experimental chronic alcoholism.
AB  - The morphological effects of ethanol ingestion on the hard palatine mucosa of
      adult male Calomys callosus were observed. Twenty rodents were divided into two
      experimental groups: the control group received solid diet, Purina rat chow, and
      tap water ad libitum; the alcoholic group received the same solid diet and
      ethanol P.A. diluted 20% in water (v/v). After 270 days of treatment, all animals
      were sacrificed and the hard palatine mucosa were prepared for TEM and SEM
      methods. The epithelial cells of the alcoholic group showed some alterations like
      cytoplasmatic lipid droplets, pycnotic nucleus and increased mitochondrial size.
      The lamina propria also presented intense lipid droplets accumulation. The
      morphological changes suggested that chronic ethanol consumption was able to
      modify the integrity of the mucosa.

PMID- 11995639
TI  - "Senseless" antiviral polyribonucleotides: poly (1-propargylinosinic acid).
AB  - Previous work has shown that novel amphipathic oligo and polyribonucleotides
      exhibiting secondary structure in solution are potent inhibitors of HIV and HCMV
      replication and cytopathicity in tissue culture. It was hypothesized that the
      mechanism(s) of action for these compounds might be inhibition of retroviral
      reverse transcriptase (RT) and/or viral uptake by cells. Pursuit of the essential
      pharmacophore has led to the discovery of poly (1-propargylinosinic acid) (10),
      an HIV and HCMV-active polyribonucleotide lacking the secondary structure
      previously thought to be essential for the observed antiviral activity.

PMID- 11995640
TI  - [The historiography of Arabic medicine and the challenges of the XXI century].
AB  - This is a critical review of the work and methods of past and present Western
      historians of Arabic medicine. It points out traditional errors, prejudices and
      limitations, and proposes to modernize the way we approach this field of
      research. Up to now, many Western scholars have deemed that Arabic medicine could
      be understood by knowing the important theoretical treatises (even in unreliable
      translations) and by reading the frequently outdated secondary literature. Modern
      research must turn to the texts that reflect the actual medical practices, focus
      on social aspects of medicine or reflect the actual medical practices, focus on
      social aspects of medicine or the interaction of learned and folkloric medicine,
      and must even try to find out the truth about the questionable statements we read
      in our textbooks. The field urgently needs interdisciplinary and international
      cooperation and wider diffusion of the recent bibliography.

PMID- 11995641
TI  - [Cristobal de Vega (1510-1573), physician to prince Don Carlos (1545-1568)].
AB  - This paper represents biographical aspects concerning the always-delicate health
      of Prince Don Carlos (1545-1568), first-born son of the King Felipe II of Spain
      (1527-1598). The main conditions and circumstances of his pathobiography were
      drawn from interesting data offered by one of his royal doctors, the former
      professor of the University of Alcala, Cristobal de Vega (1510-1573), throughout
      his significant medical career. In particular, the report on the quartan fevers
      suffered by Don Carlos in Doctor Vega's Commentaria in librum Aphorismorum
      (1568), provides considerable and previously unknown clinical data on the
      disease.

PMID- 11995642
TI  - [His Majesty's distillers: distillation and chemical medicine in the court of
      Phillip II].
AB  - The present work studies the appearance and development of Paracelsian Practices
      in the Spanish Court through a linked series of events that took place between
      1564 and 1602. These were: the creation of Philippine distillation laboratories,
      the ordenance of the protophysician Francisco de Valles regarding distilled
      waters; the concession of a patent to Diego de Santiago for the invention of a
      steam distillery; the publication of the last treatise by Francisco de Valles,
      dedicated to weights, measures, and distilled waters; the appearance of a
      distiller on the founding staff of the Royal Apothecary, in charge of preparing
      all the distilled waters and chemical medicines; and the creation of a new post
      within the Court health organigram, that of Distiller Major.

PMID- 11995643
TI  - [Gutierrez Bueno (1745-1822), textbooks and a new public for chemistry in the
      last third of the 18th century].
AB  - This paper is a part of a general research project on the role that chemistry
      played in the transition of materia medica to experimental pharmacology during
      19th century Spain. Within this general framework, the paper deals with the main
      characteristics of Spanish textbooks aimed at pharmaceutical and medical
      students. In a former study, published in this journal, we outlined the
      institutional context in which these books were read, written and published. Some
      of these issues are developed in the present paper through analysis of the "Curso
      de quimica" written by Pedro Gutierrez Bueno. New light is shed on the public for
      chemistry during the late XVIII century Spain and their role in shaping the
      contents and organisation of chemistry textbooks.

PMID- 11995644
TI  - Review: continuous nasogastric milk feeding leads to a longer time to reach full
      feeds in premature infants < 1500 g.

PMID- 11995645
TI  - a 30 mg/kg loading dose of acetaminophen was more effective than a 15 mg/kg
      maintenance dose in febrile children.

PMID- 11995646
TI  - Regular drinking of cranberry-lingonberry juice concentrate reduced recurrent
      urinary tract infections in women.

PMID- 11995647
TI  - Review: pressurised metered dose inhalers are as effective as other hand held
      inhalers for delivering corticosteroids in stable asthma.

PMID- 11995648
TI  - Review: pressurised metered dose inhalers are as effective as other hand held
      inhalers for delivering beta2 agonist bronchodilators in stable asthma.

PMID- 11995649
TI  - Review: behavioural interventions show the most promise for chronic fatigue
      syndrome.

PMID- 11995650
TI  - A short term education intervention but not peer discussion improved vitality and
      pain in women with breast cancer.

PMID- 11995651
TI  - Warming patients before clean surgery reduced the incidence of postoperative
      wound infection.

PMID- 11995653
TI  - Thromboprophylaxis with low dose unfractionated heparin plus compression
      stockings reduces thromboembolic complications of colorectal surgery.

PMID- 11995652
TI  - Review: antibiotics reduce wound infections and intra-abdominal abscesses in
      patients having appendectomy.

PMID- 11995654
TI  - Review: several techniques optimise oxygenation during suctioning of patients.

PMID- 11995655
TI  - Prone positioning for acute respiratory failure improved short term oxygenation
      but not survival.

PMID- 11995656
TI  - Intensive insulin treatment reduced mortality and morbidity in critically ill
      patients.

PMID- 11995657
TI  - Review: multidisciplinary disease management programmes do not reduce death or
      recurrent myocardial infarction but reduce admission to hospital.

PMID- 11995658
TI  - A specialist nurse intervention reduced hospital readmissions in patients with
      chronic heart failure.

PMID- 11995659
TI  - Dietary fibre supplementation with psyllium or gum arabic reduced incontinent
      stools and improved stool consistency in community living adults.

PMID- 11995660
TI  - Review: some herbal medicines and plant extracts reduced pain and disability and
      improved function in osteoarthritis.

PMID- 11995661
TI  - A support programme for patients with dementia and their caregivers lowered
      institutionalisation rates initially.

PMID- 11995662
TI  - Children infected with meningitis before 1 year of age were at increased risk of
      disability at 5 years of age.

PMID- 11995663
TI  - While leaving abusive male partners, women engaged in a 4 stage process of
      reclaiming self.

PMID- 11995664
TI  - Fathers experienced in stillbirth as a waste of life and needed to protect their
      partners and express grief in their own way.

PMID- 11995665
TI  - Practitioners' actions inhibited patient participation in self care decision
      making.

PMID- 11995666
TI  - The experiences of patients with rheumatoid arthritis admitted to hospital
      focused on 5 interrelated themes.

PMID- 11995667
TI  - Providers tried to help patients and families make realistic end of life
      decisions.

PMID- 11995668
TI  - Tuberoside M, a new cytotoxic spirostanol saponin from the seeds of Allium
      tuberosum.
AB  - Tuberoside M (1), isolated from the seeds of Allium tuberosum, shows a
      significant inhibitory effect on the growth of the human promyelocytic leukemia
      cell line (HL-60) with IC50 value of 6.8 microg/ml. On the basis of spectral data
      and chemical reaction, its structure was established as (25S)-5beta-spirostane
      1beta,3beta-diol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside.

PMID- 11995669
TI  - Asthma screening of high school athletes: identifying the undiagnosed and poorly
      controlled.
AB  - BACKGROUND: It is believed that there are many high school-age athletes who have
      undiagnosed asthma or exercise-induced asthma (EIA). The screening of these
      athletes for EIA will allow them to be identified and treated. OBJECTIVES: 1) To
      obtain reliable peak expiratory flow rate (PEFR) measurements and administer
      questionnaires to high school-age athletes to evaluate their asthma risk. 2) To
      identify high-risk athletes for having EIA or asthma by a free run challenge
      test. 3) To evaluate whether an athlete's present asthma control is adequate. 4)
      To evaluate these tools for their value as screening tools for asthma or EIA.
      METHODS: Eight hundred one student athletes from 10 suburban Pittsburgh schools
      were screened for more than 18 months for asthma as part of their
      preparticipation sports physicals. The screening included all athletes from all
      high school sports. The athletes were given a brief questionnaire, had PEFR
      measured, and then participated in a free running exercise challenge. RESULTS:
      Forty-six of 801 athletes had asthma or EIA, Of the remaining 755 athletes, 49
      athletes were identified as having undiagnosed asthma. In the previously
      unrecognized athletes with EIA, the positive and negative predictive value of the
      questionnaire was 42% and 97%, respectively. Eighty-five percent (39 of 46) of
      the known asthmatic athletes, using their recommended medication, failed their
      free running test by a >15% drop of their PEFR. CONCLUSIONS: The free running
      test is a good test for identifying and assessing the athlete with EIA. The PEFR
      meter is not a good screening tool for EIA in the high school athlete. A
      questionnaire may be a good negative screening tool, but further development is
      needed before it can be used for widespread screening.

PMID- 11995670
TI  - Intranasal fluticasone propionate is effective for perennial nonallergic rhinitis
      with or without eosinophilia.
AB  - BACKGROUND: Although response to intranasal corticosteroid therapy has been
      reported in patients with nonallergic rhinitis with eosinophilic syndrome
      (NARES), efficacy specifically in non-NARES patients has not been fully
      characterized. OBJECTIVE: To evaluate the efficacy of intranasal fluticasone
      propionate (FP) in the treatment of patients with perennial nonallergic rhinitis,
      with and without nasal eosinophilia. METHODS: Data from 983 patients in three
      randomized, double-blind, placebo-controlled PNAR trials were integrated.
      Patients received a total daily dose of FP 200 microg (n = 332), FP 400 microg (n
      = 325), or placebo (n = 326) for 28 days. Patients were > or =12 years of age
      with perennial rhinitis and negative skin tests to all allergens relevant to the
      geographic region. Nasal eosinophils were evaluated using a five-point scale.
      Patients were classified as non-NARES with a point score of 0 (n = 674; 69%);
      patients with a point score between I and 4 were classified as NARES (n = 309;
      31%). Efficacy of FP was evaluated by the mean change in total nasal symptom
      score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and
      rhinorrhea. RESULTS: Patients with either NARES or non-NARES had similar
      statistically significant improvement with FP 200 microg or 400 microg compared
      with placebo; thus, the total group comprising both varieties of rhinitis
      responded to FP. In the total population, both FP treatment groups showed
      significantly greater improvement in TNSS compared with placebo during each week
      of treatment (P < or = 0.002), with mean changes in TNSS for day 22 to day 28
      ranging from -84 and -85 in the FP 200 microg and FP 400 microg groups,
      respectively, to -64 in the placebo group. The three study treatment groups had
      similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at
      baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment
      group were similar to changes seen in the total population. In the NARES
      subgroup, mean changes in TNSS for the FP 200 microg and placebo groups were
      similar to changes seen in the total population; mean change in TNSS for the FP
      400 microg group was somewhat greater than changes seen in the total population.
      CONCLUSIONS: Intranasal FP is an effective treatment for perennial nonallergic
      rhinitis with or without nasal eosinophilia (NARES or non-NARES).

PMID- 11995673
TI  - Bibliography. Current world literature. Neonatology and perinatology.

PMID- 11995671
TI  - Therapeutic response to thalidomide in Melkersson-Rosenthal syndrome: a case
      report.
AB  - BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown
      etiology characterized by a triad of symptoms: recurrent orofacial swelling,
      relapsing facial palsy. and a fissured tongue. A differential diagnosis must be
      made with other granulomatous diseases, such as sarcoidosis and oral Crohn
      disease; however, the histologic findings of noncaseating, sarcoidal granulomas
      support the diagnosis of MRS. RESULTS: Many therapeutic modalities have been
      described for this disease. In this case report, we present a patient with MRS
      that was treated with thalidomide because of the identification of tumor necrosis
      factor a in the lesion by immunohistochemical analysis. This is the first
      reported detection of tumor necrosis factor a in an MRS lesion, as well the first
      reported use of thalidomide to treat this clinical condition.

PMID- 11995675
TI  - [83rd German Radiology Congress. 8-11 May 2002, Wiesbaden. Abstracts].

PMID- 11995674
TI  - Bibliography. Current world literature. Nephrology.

PMID- 11995676
TI  - Variation in asthma beliefs and practices among mainland Puerto Ricans, Mexican
      Americans, Mexicans, and Guatemalans.
AB  - This study reports on community surveys of 160 representative Latino adults in
      Hartford, CT, Edinburg, TX, Guadalajara, Mexico; and in rural Guatemala. A 142
      item questionnaire covered asthma beliefs and practices (e.g., causes, symptoms,
      and treatments). The cultural consensus model was used to analyze the agreement
      among respondents within each sample and to describe beliefs. Beliefs were then
      compared across the four samples. Analysis of the questionnaire data shows that
      there was overall consistency or consensus regarding beliefs and practices among
      individuals at each site (intraculturally) and to a lesser extent across
      respondents of all four different Latino cultural groups (i.e., interculturally).
      This pattern of response is indicative of a shared belief system among the four
      groups with regard to asthma. Within this shared belief system though, there is
      systematic variation between groups in causes, symptoms, and treatments for
      asthma. The most widely recognized and shared beliefs concerned causes of asthma.
      Notable differences were present between samples in terms of differences in
      beliefs about symptoms and treatments. The biomedical model is shown to be a part
      of the explanatory model at all sites; in addition to the biomedical model,
      ethnocultural beliefs such as the humoral ("hot/cold") aspects and the importance
      of balance are also evident. The Connecticut Puerto Ricans had a greater degree
      of shared beliefs about asthma than did the other three samples (p < 0.00005). It
      was concluded that the four Latino groups studied share an overall belief system
      regarding asthma, including many aspects of the biomedical model of asthma. In
      addition, traditional Latino ethnomedical beliefs are present, especially
      concerning the importance of balance in health and illness. Many beliefs and
      practices are site-specific, and caution should be used when using inclusive
      terms such as "Hispanic" or "Latino," since there is variation as well as
      commonality among different ethnic groups with regard to health beliefs and
      practices.

PMID- 11995677
TI  - Veterinary nurse training in the 21st century: which direction should it take?

PMID- 11995678
TI  - Serovars of Salmonella isolated from Danish turkeys between 1995 and 2000 and
      their antimicrobial resistance.
AB  - The prevalence of Salmonella serovars and their antimicrobial resistance patterns
      were investigated among Danish turkeys between 1995 and 2000, by sampling the
      flocks approximately 14 days before they were slaughtered. Within the flocks, the
      prevalence of salmonella varied from 7.1 per cent to 25 per cent, and 24
      different serovars were detected. The five most prevalent, which accounted for
      58.5 per cent of the isolates were Salmonella Heidelberg (16.2 per cent of the
      isolates), Salmonella Agona (15.8 per cent), Salmonella Derby (12.4 per cent),
      Salmonella Muenster (7.3 per cent) and Salmonella Anatum (6.8 per cent). In
      addition, a few rough isolates and isolates belonging to the antigenically
      incomplete formulae 6,7:-:- and 4,12:b:- were found. The level of antimicrobial
      resistance was low; the highest resistance was recorded to ampicillin (13.7 per
      cent) and streptomycin (9.0 per cent) followed by tetracycline (8.5 per cent),
      sulphonamides (7.7 per cent) and spectinomycin (4.7 per cent). Resistance to
      quinolones was very low: four isolates were resistant to nalidixic acid, and only
      one was resistant to enrofloxacin. No resistance was recorded to colistin,
      apramycin, ceftiofur, florfenicol, or amoxycillin with clavulanic acid. Only 24
      isolates were resistant to two or more compounds in various combinations of up to
      six compounds; one Salmonella Havana isolate was resistant to six compounds. Six
      isolates were serovar Typhimurium, but none of them belonged to phage type DT104.

PMID- 11995679
TI  - Domoic acid toxicity in Californian sea lions (Zalophus californianus): clinical
      signs, treatment and survival.
AB  - Eighty-one Californian sea lions (Zalophus californianus) with signs of domoic
      acid toxicity stranded along the coast of California in 1998 when there were
      blooms of the domoic acid-producing alga Pseudonitzschia australis off-shore. In
      2000, a further 184 sea lions stranded with similar clinical signs, but the
      strandings occurred both during detectable algal blooms and after the blooms had
      subsided. The clinical signs in these 265 Californian sea lions included
      seizures, ataxia, head weaving, decreased responsiveness to stimuli and
      scratching behaviour. Affected animals had high haematocrits, and eosinophil
      counts, and high activities of serum creatine kinase. They were treated
      supportively by using fluid therapy, diazepam, lorazepam and phenobarbitone.
      Fifty-five of the 81 sea lions (68 per cent) affected in 1998 and 81 of the 184
      (44 per cent) affected in 2000 died despite the treatment. Three of the 23 sea
      lions which survived in 1998 were tracked with satellite and radiotransmitters;
      they travelled as far south as San Miguel Island, California, and survived for at
      least three months. Eleven of the 129 animals which were released stranded within
      four months of being released.

PMID- 11995680
TI  - Treatment of laryngeal hemiplegia in horses by prosthetic laryngoplasty,
      ventriculectomy and vocal cordectomy.
AB  - The medical records of 80 horses treated for left laryngeal hemiplegia by
      prosthetic laryngoplasty, ventriculectomy and vocal cordectomy were examined,
      first to compare the subjective and objective success rates for groups of horses
      of different ages and used for different purposes, and secondly, to compare the
      efficacy of including vocal cordectomy in the surgical protocol with published
      success rates for laryngoplasty and ventriculectomy alone. Subjectively, 70 per
      cent of the horses were said to have had a successful surgical outcome. The
      success rate for thoroughbred racehorses (66 per cent) was lower than for other
      breeds (90 per cent) on the basis of a subjective assessment by owners and
      trainers. Thoroughbreds two years old or younger had a success rate of 69 per
      cent, but older thoroughbreds had a success rate of 61 per cent. Of the 17 horses
      for which an objective performance index could be calculated, 10 (59 per cent)
      had an improved performance postoperatively. There was a nearly significant
      association between the objective and subjective assessments (P=0.078). Six of 69
      horses (8.7 per cent) continued to make a respiratory noise after surgery. The
      subjective assessment of success did not appear to correlate with the objective
      measure of success used in this study and age had no apparent association with a
      successful surgical outcome. Inclusion of a vocal cordectomy in the surgical
      protocol may be more important in the eradication of postoperative respiratory
      noise than in improving clinical success rates.

PMID- 11995681
TI  - Clinical and pathological investigations of 'kangaroo gait' in sheep.

PMID- 11995682
TI  - Seasonal variation in development of in vitro produced bovine embryos.

PMID- 11995683
TI  - Isolation of Staphylococcus schleiferi subspecies coagulans from two cases of
      canine pyoderma.

PMID- 11995684
TI  - Early diagnosis of feline medulloblastoma in the vermis.

PMID- 11995685
TI  - Vets and the future of farming.

PMID- 11995686
TI  - Cattle transport in the UK.

PMID- 11995688
TI  - Future of the RCVS library.

PMID- 11995687
TI  - Future of the RCVS library.

PMID- 11995689
TI  - TB in badgers and cattle.

PMID- 11995690
TI  - Training for future disease outbreaks.

PMID- 11995691
TI  - Increased incidence of Streptococcus agalactiae.

PMID- 11995692
TI  - Support for those accused of bullying.

PMID- 11995694
TI  - Comparative effects of phthalate monoesters on gap junctional intercellular
      communication and peroxisome proliferation in rodent and primate hepatocytes.
AB  - Several phthalate esters, compounds used as plasticizers in a variety of
      commercial products, have been shown to induce hepatic tumors in rodents. In this
      study, the comparative effects of phthalate monoesters on inhibition of gap
      junctional intercellular communication and induction of peroxisomal beta
      oxidation were assessed in primary cultured hepatocytes from rats, mice,
      hamsters, cynomolgus monkeys, and humans. A human liver cell line was also
      utilized. Eight monoesters examined included mono-2-ethylhexyl phthalate (MEHP),
      mono-n-octyl phthalate (MNOP), mono-isononyl phthalate (MINP, 3 types, -1, -2,
      and -3), mono-isoheptyl phthalate (MIHP), mono-isodecyl phthalate (MIDP), and
      mono-(heptyl, nonyl, undecyl) phthalate (M711P). Gap junctional intercellular
      communication was measured 4 and 24 h after treatment by lucifer yellow dye
      coupling. Gap junctional intercellular communication was inhibited in rat and
      mouse hepatocytes by all eight monoesters in a concentration-dependent manner. In
      most cases, gap junctional intercellular communication was significantly reduced
      at the lowest concentrations tested (50 pM). Inhibition of gap junctional
      intercellular communication in rodent cells was substantially reversed within 24
      h of monoester removal. In contrast, cell-to-cell communication was not inhibited
      in hamster, cynomolgus, or human hepatocytes or in a human liver cell line at any
      concentration examined. In rat hepatocytes, peroxisomal beta-oxidation was
      elevated after treatment with MEHP, MINP, MIHP, and MIDP but not MNOP or M711P,
      and with all but MIHP in mouse hepatocytes. The eight phthalates produced no
      marked change on peroxisomal beta-oxidation in hepatocytes from other species.
      These data provide additional evidence that the toxicological effects of
      phthalate esters are species specific.

PMID- 11995695
TI  - [From conquering metastatic disease to adjuvant therapy: clinical evolution of
      docetaxel in breast cancer].

PMID- 11995696
TI  - [Role of docetaxel in the treatment of gastric cancer].

PMID- 11995697
TI  - [Chemotherapy of prostate cancer: potential role of docetaxel].

PMID- 11995698
TI  - [3rd National Congress of Medical Oncology. Issues in Gynecologic Oncology.
      Naples, November 7, 2000].

PMID- 11995699
TI  - [Oxaliplatin: preclinical in vitro studies].

PMID- 11995700
TI  - [Oxaliplatin and fluorouracil: bolus coadministration regimens].

PMID- 11995701
TI  - [Oxaliplatin: combinations with thymidylate synthetase inhibitors: two
      consecutive phase II studies].

PMID- 11995702
TI  - [Chronotherapy].

PMID- 11995703
TI  - [Radiochemotherapy in rectal cancer].

PMID- 11995704
TI  - [Proceedings of the 3rd National Conference of Medical Oncology. Irinotecan:
      present and future. Napoli, Italy, 5 November 2001].

PMID- 11995705
TI  - [Colorectal cancer: irinotecan in combination with newer drugs].

PMID- 11995706
TI  - [Irinotecan in the treatment of stomach cancer].

PMID- 11995707
TI  - [Role of irinotecan in the treatment of small cell carcinoma].

PMID- 11995708
TI  - [Second-line and beyond: Docetaxel in the treatment of non-small-cell lung
      cancer].

PMID- 11995709
TI  - [Docetaxel: a new weapon in the treatment of head and neck tumors].

PMID- 11995711
TI  - American Society for Gastrointestinal Endoscopy annual meeting. May 19-23, 2002.
      San Francisco, California, USA. Abstracts.

PMID- 11995710
TI  - World Health Organization takes on 'tobacco epidemic'.

PMID- 11995712
TI  - Abstracts of the 43rd Spring Meeting of the German Society for Experimental and
      Clinical Pharmacology and Toxicology. 12-14 March 2002, Mainz, Germany.

PMID- 11995713
TI  - Abstracts of the 68th Annual Meeting of the German Society of Cardiology--Heart
      and Circulatory Research. 4-6 April 2002, Mannheim.

PMID- 11995714
TI  - Abstracts of the XXI Congress of the International Society for Analytical
      Cytology. May 2002.

PMID- 11995715
TI  - Physicians and joint negotiations.

PMID- 11995716
TI  - Physicians and joint negotiations.

PMID- 11995717
TI  - Medicare managed care: Medicare+Choice at five years.

PMID- 11995718
TI  - Whitner v. State.

PMID- 11995719
TI  - Must one twin die?

PMID- 11995720
TI  - Is anyone in there?

PMID- 11995721
TI  - Share the risk: revealing the secrets of our genes to insurers doesn't add up.

PMID- 11995722
TI  - Premium genes.

PMID- 11995723
TI  - No more kicks: there are treatments on the way that promise to destroy the allure
      of addictive drugs for good. Problem solved?

PMID- 11995725
TI  - Designing a dilemma.

PMID- 11995726
TI  - The need to know.

PMID- 11995727
TI  - Back to the source.

PMID- 11995728
TI  - About time.

PMID- 11995729
TI  - Put it to the vote.

PMID- 11995730
TI  - Give us your genes.

PMID- 11995731
TI  - Not now, Dr. Miracle. Cloned babies are a bad idea when the science is still in
      its infancy.

PMID- 11995732
TI  - Flirting with death. Live vaccines might eradicate HIV in many countries. But are
      the risks too great?

PMID- 11995733
TI  - Brave new babies. An automated IVF chip could lead to production-line embryos.

PMID- 11995734
TI  - The awful truth. Why would anyone in their right mind want to clone a baby when
      animal cloning can go disastrously wrong?

PMID- 11995736
TI  - Making babies. There are more ways than ever to create the next generation.

PMID- 11995737
TI  - Waiting for a miracle: time is running out for organ transplants from animals.

PMID- 11995738
TI  - Is this the one? We may have found the cell that will revolutionize medicine.

PMID- 11995739
TI  - Retirement and mental health.
AB  - OBJECTIVES: This research examines whether retirement is associated with mental
      health and how one's daily pursuits mediate this association. It tests two
      perspectives from the sociology of work and the sociology of mental health.
      METHODS: Using data from two surveys, the 1995 Aging, Status, and Sense of
      Control and the 1987-1988 National Survey of Families and Households, regression
      analysis was used to examine retirement, activities, and well-being. RESULTS: In
      support of the view that work is alienating and retirement liberating, retirees
      experienced less anxiety and distress and higher positive affect. Retirees' lower
      anxiety and distress were explained by activity characteristics. In support of
      the view that work is empowering and retirement demoralizing, retirement is
      associated with lower sense of control in both data sets, in part because of the
      daily pursuits. Retirement was not associated with depressive symptomatology.
      DISCUSSION: Suggestions for creating opportunities that enhance well-being are
      discussed.

PMID- 11995740
TI  - Body-mass index and 4-year change in health-related quality of life.
AB  - OBJECTIVE: To determine the effect of body-mass index (BMI) categories (a proxy
      for adiposity) on 4-year changes in health-related quality of life (HRQL)
      independent of baseline disease severity. DESIGN: Secondary analyses of a
      prospective, longitudinal study. PARTICIPANTS: Data on 7,895 adults ages 51 to 61
      years who responded to the Health and Retirement Surveys in 1992, 1994, and 1996
      were included. RESULTS: Estimates of the effect of BMI on changes in HRQL were
      adjusted by disease severity. Each BMI category was associated with an increasing
      risk of decline in perceived health, with the highest risk in the higher
      categories. A BMI of between 30 and 35 was associated with a risk of decline in
      mobility. CONCLUSIONS: The findings suggest a significant impact of BMI on
      changes in HRQL that is independent of disease severity and baseline HRQL.

PMID- 11995741
TI  - Educational attainment, continued learning experience, and cognitive function
      among older men.
AB  - OBJECTIVES: This article assesses the effects of educational attainment,
      posteducational training experience, and occupational status on cognitive
      function among older men, controlling for demographic and health factors.
      Conditional relationships between educational attainment and factors that
      importantly influence cognitive function are also investigated. METHODS: Data
      from a nationally representative sample of 1,839 older men are used to explore
      life-course effects of occupational and training experiences during the 1960s,
      1970s, and 1980s. RESULTS: A positive relationship is found between formal
      educational attainment and cognitive function, but this association is
      conditional on subsequent training experience, ethnicity, and symptoms of
      depression. Training experiences are also positively associated with cognitive
      function. DISCUSSION: Continued pursuit of education and training may offer
      opportunities to promote cognitive function throughout the life course,
      especially among those with low educational attainment early in life.

PMID- 11995742
TI  - Adult day care for the frail elderly: outcomes, satisfaction, and cost.
AB  - OBJECTIVES: To assess outcomes and satisfaction among frail elderly day care
      clients and their informal caregivers and the impact of adult day care on the
      cost of health services. METHODS: One-hundred eight elderly participants were
      randomly assigned to the experimental group (immediate admission to an adult day
      care center) and 104 participants to the control group (3 months on a waiting
      list). RESULTS: Participants' and caregivers' subjective perceptions of the day
      center's effects were positive. However, using standard research instruments,
      there was no evidence of an effect of day center attendance on the client's
      anxiety, depression, or functional status; on caregiver burden; or on the cost of
      health services. DISCUSSION: It is difficult to demonstrate objectively the
      benefits of programs and interventions that are perceived by clients, caregivers,
      and staff to have positive effects. In future studies, maintenance of high levels
      of participation should be incorporated as an explicit program goal.

PMID- 11995743
TI  - The relationship between age and depressive symptoms: a test of competing
      explanatory and suppression influences.
AB  - OBJECTIVE: The objective is to examine competing explanatory and suppression
      influences on a negative, linear association between age and depressive symptoms.
      METHODS: Two samples were used: a community sample of physically disabled
      individuals and a comparison sample matched on age, sex, and area of residence.
      RESULTS: Fewer economic hardships and fewer experiences of negative interpersonal
      exchanges among older disabled and nondisabled respondents account for the
      negative relationship between age and depressive symptoms. Higher scores on a
      composite measure of religiosity among older disabled adults also account for
      part of the negative age effect. Conversely, a lower sense of mastery among older
      respondents in both samples suppresses the size of the negative age slope.
      DISCUSSION: Findings are discussed in terms of stress process and socioemotional
      selectivity theories, which predict that personal and social arrangements
      influence the experience of emotions differentially across the life course.

PMID- 11995744
TI  - An evaluation of universal health insurance in the elderly: burden of disease,
      utilization, and costs in the Republic of Korea.
AB  - OBJECTIVE: This article evaluates Korea's national health insurance system for
      the elderly by simultaneously examining disease patterns, demand for care,
      utilization, costs of care, and facility type. METHODS: Claim records (N =
      8,306,976) for 1995 to 1997 were obtained from the Youndeoung-Po district for
      four insurance categories. Utilization is examined using a probit model; a linear
      regression model is used to compare costs. FINDINGS: Insurees averaged 10.6
      medical visits per year, most commonly for acute respiratory diseases. The
      elderly were more likely to seek care for circulatory problems, use more
      inpatient services, and rely on hospitals for outpatient care. Insurance costs
      for the elderly poor were markedly higher, and overall care for the elderly was
      higher per visit. DISCUSSION: By simultaneously analyzing utilization rates,
      disease patterns, and relative costs of care, policymakers may be able to avert a
      financing crisis. Stronger pricing strategies and better disease targeting would
      adjust utilization and increase efficiency of health expenditures.

PMID- 11995745
TI  - A combined medical and surgical approach to hydatid disease: 12 years' experience
      at the Hospital for Tropical Diseases, London.
AB  - BACKGROUND: There is no consensus as to the most appropriate treatment for the
      varied and often complicated presentations of hydatid disease in Britain. We
      looked at our own results over a 12-year period to see if a consistent and
      logical plan had emerged. PATIENTS AND METHODS: 70 patients presenting between
      1986 and 1998 were analysed retrospectively, with regard to their presentation,
      diagnosis, treatment and outcome, with particular reference to the use of
      chemotherapy, and to the difficulties of post-treatment assessment by serology
      and imaging. RESULTS: 37 patients had been treated previously. 35 had hepatic
      cysts and 26 multiple cysts. 4 patients were treated by surgery alone, 44 by
      chemotherapy and surgery, and 14 by chemotherapy alone. The combined use of
      albendazole and praziquantel pre-operatively reduced significantly the number of
      cysts that contained viable protoscolices: 1/25 versus 5/8 that received
      albendazole alone (P = 0.00013). During the 12-year period, it became our policy
      to aim for 3 months drug treatment (albendazole throughout with praziquantel for
      2 weeks), re-assess and proceed either to surgery or to continue with
      chemotherapy. CONCLUSIONS: It is possible to construct an algorithm for the
      management of patients with hydatid disease by chemotherapy and surgery, but the
      assessment of results by indirect techniques remains difficult.

PMID- 11995746
TI  - Splenectomy after paediatric trauma: could more spleens be saved?
AB  - AIMS: Guidelines for the emergency management of paediatric splenic trauma became
      widely available in 1993. A regional survey was undertaken to assess the
      application of Advanced Paediatric Life Support guidelines to children who had
      undergone splenectomy after trauma. PATIENTS AND METHODS: All children who had
      undergone splenectomy for a ruptured spleen at 8 district hospitals and 2
      teaching hospitals in our region between January 1994 and January 1999 were
      identified from histopathology departmental records. With appropriate permission
      their case notes were reviewed. RESULTS: Eleven children (9 males) were
      identified, all from district hospitals, with a median age at presentation of
      11.8 years (range, 6.6-16.8 years). All presented within 6 h of blunt abdominal
      trauma. Median systolic blood pressure, pulse rate, haemoglobin concentration and
      injury severity score (ISS) on admission were 115 mmHg (range, 80-140 mmHg), 108
      bpm (range, 84-150 bpm), 12.1 g/dl (range, 10.7-12.8 g/dl) and 17 (range, 17-29),
      respectively. Three children had additional relatively minor injuries. On
      admission, 3 children received an intravenous fluid bolus of 20 ml/kg and the
      remainder received only maintenance fluid requirements or less. Five children
      were investigated by ultrasound imaging, one by double contrast CT scan, and
      three by laparoscopy. Two children had no imaging studies prior to laparotomy.
      Laparotomy was performed by a consultant surgeon in 7 cases and by a specialist
      registrar in 4 cases. Ten children underwent total splenectomy and one child had
      a partial splenectomy. Median hospital stay was 7 days (range, 5-10 days). The
      child with an ISS of 29 developed a persistent pancreatic fistula and
      subsequently required a distal pancreatectomy. All children received Pneumovax
      and penicillin prophylaxis. CONCLUSIONS: All children made a full recovery
      without surgical morbidity. However, none of these cases fulfilled the
      recommended criteria for laparotomy in children with blunt abdominal trauma and
      splenectomy may have been avoidable.

PMID- 11995747
TI  - The quality of hospital records of urethral catheterisation.
AB  - BACKGROUND: This prospective and retrospective study carried out over a period of
      one month (50 patients) looked at the quality of hospital records of urethral
      catheterisation with reference to the hospital protocol. The patients were
      catheterised on general surgical wards as well as in theatre. RESULTS: The
      quality of hospital records of this procedure was poor and a number of
      complications noted. CONCLUSIONS: Good documentation of urethral catheterisation
      would result in a better quality of audit and, therefore, identify potential ways
      of minimising complications. We recommend this by regular audit of hospital
      records, re-inforcement of protocols and informed consent of this procedure, with
      particular reference to theatre.

PMID- 11995748
TI  - A survey of surgical activity in UK community hospitals.

PMID- 11995749
TI  - A survey of emergency vascular service provision.
AB  - Recommendations exist for the optimal management of vascular surgical emergency
      patients. A telephone survey of on-call surgical registrars was performed to
      assess the current state of emergency vascular service provision across the
      Wessex and South West regions in the UK. Of the 24 hospitals surveyed, 10 had
      formal on-call arrangements for vascular surgical cover, 14 had informal
      arrangements where the general surgical consultant on-call provided cover and
      could contact a vascular surgeon if they were available and 3 hospitals had no
      such arrangements. No difficulties had been experienced by the on-call staff
      surveyed with any of the existing arrangements. Only 5 of the hospitals had
      formal on-call arrangements for interventional radiologists. We conclude that
      current emergency vascular service provision is suboptimal compared to national
      guidelines and patients may be subject to unequitable access to services. This
      may not be tenable in the new era of clinical governance.

PMID- 11995750
TI  - Fitness to drive: a survey of the knowledge and practice of vascular surgeons
      regarding patients with carotid disease and aortic aneurysms.

PMID- 11995751
TI  - Thromboembolism in orthopaedics--observation and experiment.
AB  - Surgical science has evolved from the meticulously recorded anatomical and
      pathological experiments applied by Hunter to the use of large observational
      studies and randomised clinical trials. These modern epidemiological techniques,
      supported by appropriate statistics, are helping us to answer many questions in
      surgery. Perhaps nowhere in surgery have these techniques been applied as
      thoroughly as in orthopaedic thromboembolism.

PMID- 11995752
TI  - Combined orthogeriatric care in the management of hip fractures: a prospective
      study.
AB  - AIMS: To evaluate the efficacy of combined care between orthopaedic surgeons and
      geriatricians in the management of patients with fractured necks of femur.
      PATIENTS AND METHODS: A prospective study of the admissions to a district general
      hospital with hip fractures was carried out over a 5-year period. In the years
      1992-1994, medical problems in this patient group were managed by a consultation
      only service. At the end of 1994, a consultant geriatrician was appointed to
      manage these patients jointly with the orthopaedic surgeons, and the study was
      then carried through until the end of 1996. Information about the patients from
      admission to discharge or death was gathered prospectively using a proforma for
      the 3 years prior to orthogeriatric care, and the 2 years after. Main outcome
      measures were mortality, length of stay and discharge destination. These were
      compared for the two periods--pre- and post-orthogeriatric care. RESULTS: No
      significant differences were noted in mortality, length of stay or discharge
      destination. CONCLUSIONS: Combined orthogeriatric care according to our model did
      not have an impact on our chosen outcome measures.

PMID- 11995753
TI  - Locked lateral patellar dislocation with impaction fracture of patella.
AB  - Irreducible lateral patellar dislocation is rare. It has previously been
      described with rotation around a vertical axis. We describe a case of irreducible
      lateral patellar dislocation in a 66-year-old lady with an impaction fracture of
      medial facet of patella locked on the lateral femoral condyle. Closed reduction
      was unsuccessful and the patient was treated by total knee replacement. Such a
      case has not been described previously in the literature.

PMID- 11995754
TI  - Hair tying as a method of scalp wound closure.

PMID- 11995755
TI  - Making your mark again in surgery.
AB  - Accurate, durable pre-operative skin marking that withstands the necessary
      vigorous surgical skin preparation on the theatre table minimises confusion and
      the risk of mistakes occurring perioperatively, as well as assisting the surgeon
      with the technicalities of required skin incisions. Felt-tipped marker pens vary
      widely in achieving these objectives. A selection of markers, including a number
      used by junior surgical staff on the wards, was investigated.

PMID- 11995756
TI  - Body packers: grading of risk as a guide to management and intervention.
AB  - The dual aims of management of the drug smuggler are for low morbidity and
      mortality combined with a low operation rate. In our experience, presented in
      this paper, adherence to the principle of identifying the high-risk patient by
      symptoms and signs combines safety with low rates of intervention.

PMID- 11995757
TI  - Are autopsies useful? Do premorbid findings predict postmortem results in head
      and neck cancer patients?
AB  - A total of 53 autopsies were analysed in patients with head and neck squamous
      carcinoma. The discordance rate, that is the proportion of autopsies that
      revealed new information, was 53%. One-third of patients did not die of cancer.
      Clinical findings either misdiagnosed or under-diagnosed loco regional disease in
      34% of cases, and distant malignant disease in 36% of cases. It appears that the
      autopsy reveals new and useful information in the head and neck cancer patient,
      and consent should be sought.

PMID- 11995758
TI  - Arthroscopy of the knee joint.

PMID- 11995759
TI  - The small bowel wrap--an effective way of packing small bowel in the surgical
      field.

PMID- 11995760
TI  - Roadrunner to the rescue.

PMID- 11995761
TI  - The 'Tellytubby Tummy', a novel technique for laparostomy management.

PMID- 11995762
TI  - Replace fine needle aspiration cytology with automated core biopsy in the triple
      assessment of breast cancer.

PMID- 11995763
TI  - Replace fine needle aspiration cytology with automated core biopsy in the triple
      assessment of breast cancer.

PMID- 11995764
TI  - Use of the laryngeal mask airway in thyroid and parathyroid surgery as an aid in
      identification and preservation of the recurrent laryngeal nerves.

PMID- 11995765
TI  - Use of the laryngeal mask airway in thyroid and parathyroid surgery as an aid in
      identification and preservation of the recurrent laryngeal nerves.

PMID- 11995766
TI  - Use of the laryngeal mask airway in thyroid and parathyroid surgery as an aid in
      identification and preservation of the recurrent laryngeal nerves.

PMID- 11995767
TI  - From pollutant gas to biological messenger: the diverse actions of nitric oxide
      in cancer.
AB  - Nitric oxide (NO) has undergone an image change in recent years. Previously
      regarded as a toxic pollutant gas, it has now become the subject of intense
      research in many fields of medicine and science. It is a free radical, with a
      diverse range of actions in both physiological and pathological processes.
      Although over 44,000 research papers have now been written on NO, only a small
      number have originated from the surgical specialties. Its role in tumour biology
      remains incompletely understood. NO is known to have both tumour promoting and
      inhibitory effects, presumed to be dependent on its local concentration within
      the tumour. NO appears to be pivotal in the angiogenic process, and the p53
      tumour suppressor gene may influence its production. This review summarises the
      brief history of this molecule, gives an overview of its many effects in the
      common solid tumours and discusses how targeting of NO production may have
      possible future therapeutic benefit.

PMID- 11995768
TI  - Variations in implementation of current national guidelines for the treatment of
      acute pancreatitis: implications for acute surgical service provision.
AB  - OBJECTIVES: The aim of this study was to explore the implementation of the
      current national guidelines for the treatment of acute pancreatitis. By taking
      pooled data from all available individual and regional audits, the study aimed to
      identify areas of consistent variance from the 'best practice' stipulated in the
      guidelines. METHODS: All published audits of the management of acute pancreatitis
      where treatment was compared to the current British Society of Gastroenterology
      guidelines for the treatment of acute pancreatitis were identified from a search
      of MEDLINE and the published abstracts of relevant specialty meetings. RESULTS:
      Five audits providing pooled data on 545 patients were identified. Overall
      mortality from severe disease was 8% (range, 4-17%). Definitive treatment of
      gallstone disease within 4 weeks of index attack was performed in 49% (range, 16
      65%). High dependency or intensive care facilities for severe disease were
      available in 52% (range, 20-100%). CONCLUSION: This study demonstrates the
      presence of striking variations in the implementation of the current national
      guidelines for the treatment of acute pancreatitis.

PMID- 11995769
TI  - Breast augmentation should be on the NHS: a discussion of the ethics of
      rationing.
AB  - Every NHS clinician is under constant pressure to match limited resources to
      increasing demands. The GMC provides guidelines about how we should ration: 'you
      should always seek to give priority to the treatment of patients solely on the
      basis of clinical need'. However, this gives no indication as to what is 'need'.
      Often, in its application, certain assumptions are made about the nature of
      clinical need. To examine some of these assumptions in more detail, I will argue
      the case for a treatment that is on the borderline of the remit of NHS care-
      breast augmentation.

PMID- 11995770
TI  - Safe transition from open to laparoscopic fundoplication by an established
      consultant--the importance of repeated audit.
AB  - BACKGROUND: Serious complications of laparoscopic fundoplication (LF) have been
      reported by surgeons new to LF. We investigated whether the reported benefits of
      LF could be realised by an established consultant, new to LF, without
      compromising safety, control of reflux or dysphagia rates obtained after open
      surgery. PATIENTS AND METHODS: Outcome of 65 consecutive open fundoplications was
      audited. After training in LF, this audit was compared with an identical
      prospective audit of 65 patients undergoing LF. RESULTS: No significant
      differences occurred between the two groups in relief of reflux. LF resulted in:
      (i) shorter postoperative stay (median 2 days versus 7 days, P < 0.001); (ii)
      earlier return to work (median 4 weeks versus 9 weeks, P < 0.001); (iii) shorter
      duration of postoperative dysphagia (median 4 weeks versus 9 weeks, P = 0.01);
      and (iv) less intra/postoperative complications (7.7% versus 32.3%, P < 0.001).
      CONCLUSIONS: LF can be introduced safely by established consultants provided that
      adequacy of training is confirmed by repeated audit.

PMID- 11995771
TI  - Long-term follow-up of endoscopic stapled diverticulotomy.
AB  - We report a consecutive series of 31 patients who underwent endoscopic stapled
      diverticulotomy. The patients' notes were reviewed retrospectively to gather data
      on their original admission and a postal survey was conducted to establish
      patient satisfaction, their ability to swallow and re-operation data. Three
      patients were lost to follow-up. Nine of the remaining 28 died at a median of 18
      months. The remaining 21 were followed up for a median of 59 months. The data
      showed that, at 5 years, 94.4% of patients had an improvement in their
      swallowing, and 50% had an entirely normal swallow. In order to achieve this
      result, 19% of patients required a second procedure, and one patient (3.2%)
      required a third (open) procedure. Endoscopic stapled diverticulotomy has well
      established, short-term advantages. This series shows that it has a good long
      term outcome that is similar to established open techniques and probably better
      than other techniques of endoscopic diverticulotomy, i.e. diathermy or laser.

PMID- 11995772
TI  - Non-steroidal anti-inflammatory drugs and perforated diverticular disease: a case
      control study.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have a wide range of side-effects
      in the gastrointestinal tract and the large intestine. This study examines the
      hypothesis that the use of NSAIDs is associated with colonic perforation in
      diverticular disease. Histological evidence was used to confirm perforation. A
      retrospective review of case records and pathology reports identified 20 patients
      admitted over 3 consecutive years. A total of 125 age- and sex-matched patients
      diagnosed with diverticular disease not complicated by perforation formed the
      control group. The incidences of NSAID use in the two groups were compared. A
      second control group consisted of 600 age- and sex-matched randomly selected
      patients with no known diverticular disease admitted as emergencies in the same
      period. Of the 20 patients with perforation, 9 were taking NSAIDs for 4 weeks or
      longer, compared with 19 (15%) of the 125 patients who did not have perforation
      (relative risk 2.961, 95% confidence interval 1.507-5.348, P < 0.01). 19% of all
      patients with diverticular disease were taking NSAIDs compared with 10% of the
      second control group (relative risk 1.869, 95% confidence interval 1.237-2.781, P
      < 0.01). The findings indicate a strong association between the use of NSAIDs and
      the perforation of colonic diverticula. The majority of the indications for the
      use of NSAIDs were cardiovascular and musculoskeletal conditions. Prescribing
      NSAIDs to patients with diverticular disease carries an increased risk of colonic
      perforation.

PMID- 11995773
TI  - Intraspinal oxidised cellulose (Surgicel) causing delayed paraplegia after
      thoracotomy--a report of three cases.
AB  - Oxidised regenerated cellulose (Surgicel) is a commonly used haemostatic agent in
      neurosurgery, thoracic surgery, and orthopaedics. We present three cases of
      paraplegia after thoracic surgery during which oxidised cellulose had been used
      during thoracotomy for haemorrhage control, and was later found to have passed
      through the intervertebral foramen causing spinal cord compression. In all
      intraspinal and perispinal procedures, the over-liberal use of Surgicel should be
      avoided, and attempts made to remove all excess Surgicel once adequate
      haemostasis is obtained.

PMID- 11995774
TI  - Diagnosis and treatment of premenstrual dysphoria.
AB  - Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome afflicting
      5% to 10% of all fertile women. Cardinal symptoms--appearing regularly between
      ovulation and menstruation and disappearing within a few days after the onset of
      the bleeding--are depressed mood, tension, affect lability, and irritability. Of
      these symptoms, irritability is often the most prominent. Serotonin reuptake
      inhibitors (SRIs), but not nonserotonergic antidepressants, reduce the symptoms
      of PMD effectively. The onset of action of SRIs is much shorter when used for PMD
      than when used for depression, enabling women with PMD to restrict medication use
      to the luteal phase of the cycle (so-called intermittent treatment). The findings
      that SRIs are effective for PMD--and that sexual dysfunction is the most frequent
      side effect during long-term treatment--both lend support for the hypothesis that
      a major role for brain serotonin is to modulate sex steroid-driven behavior.

PMID- 11995775
TI  - Depression during pregnancy: diagnosis and treatment options.
AB  - Women often seek clinical consultation for antidepressant use both prior to
      conception and during pregnancy. Some women experience a new onset of symptoms
      during pregnancy, while those with a history of depressive symptoms are at
      increased risk. Nevertheless, clinicians are faced with the challenge of treating
      the mother without posing risks to the fetus. This review discusses risk factors
      for depression during pregnancy and the consequences of untreated depression.
      Nonpharmacologic and pharmacologic treatment options are reviewed, and guidelines
      for treating depression during pregnancy are presented.

PMID- 11995776
TI  - The use of SSRIs in depressive disorders specific to women.

PMID- 11995777
TI  - The treatment of postpartum depression: minimizing infant exposures.
AB  - The first 3 postpartum months represent a high-risk period for psychiatric
      illnesses. This article reviews the prevalence and diagnostic criteria for
      postpartum illnesses, including the "maternal blues," postpartum depression, and
      postpartum psychosis. Pharmacologic treatment of these disorders is often
      complicated by a patient's desire to breast-feed, yet there are no controlled
      trials of antidepressant treatment during lactation. Infant exposure and
      limitations to monitoring infant sera are reviewed. Lastly, a model and guide for
      reducing fetal and infant exposures is presented.

PMID- 11995778
TI  - Estrogen replacement therapy in the treatment of major depressive disorder in
      perimenopausal women.
AB  - BACKGROUND: Increased vulnerability to mood disorders has been reported during
      perimenopause. Fluctuating estrogen levels accompany the perimenopausal
      transition. Thus, estrogen replacement therapy (ERT) has been proposed as a
      potentially effective treatment for mood disorders occurring during
      perimenopause. METHOD: We examined the efficacy of ERT in the treatment of
      depression in 16 perimenopausal women with DSM-IV-defined major depressive
      disorder who were participating in the Mood Disorders Research Program at the
      Department of Psychiatry of the University of California, Los Angeles. Ten
      antidepressant- and ERT-naive women received ERT alone. Six women who were
      nonresponders or partial responders to an antidepressant received ERT in addition
      to existing treatment with fluoxetine. The Hamilton Rating Scale for Depression
      (HAM-D) was administered to all patients at baseline and weekly thereafter during
      the 8-week open-protocol trial. Partial response was operationalized as a final
      HAM-D score < or = 50% of the baseline score. Remission was defined as a final
      HAM-D score < or = 7. RESULTS: All patients exhibited clinical improvement as
      measured by HAM-D scores after the first week of treatment. Of the 10
      perimenopausal depressed women receiving ERT alone, 6 remitted, 3 partially
      responded to treatment, and 1 did not respond by the end of the trial. Of the 6
      women receiving antidepressant treatment with ERT, 1 patient remitted and 5 had a
      partial response by the end of the trial. CONCLUSION: This small study suggests
      that for some antidepressant-naive perimenopausal women with clinical depression,
      ERT may have antidepressant efficacy. In depressed women who have minimal
      response to a selective serotonin reuptake inhibitor, ERT may augment response.
      Further controlled trials are needed.

PMID- 11995779
TI  - Epidemiology of depression throughout the female life cycle.
AB  - Women are at an increased risk for first onset of major depression from early
      adolescence until their mid-50s and have a lifetime rate of major depression 1.7
      to 2.7 times greater than that for men. There is accumulating evidence that
      certain reproductive-related hormonal changes place women at increased risk for
      depression. For example, puberty marks the beginning of increased risk for
      depression in women. Most women report physical or emotional symptoms
      premenstrually, with some severe enough to be diagnosed as premenstrual dysphoric
      disorder. While pregnancy does not increase the risk for depression, women with
      past histories of depression are at risk for recurrent episodes or relapse if
      antidepressant medications are discontinued. Hormonal changes during the
      postpartum period also increase the incidence of depression. Similarly, women
      transitioning through perimenopause, particularly those with past psychiatric
      histories, report depressive symptoms. Prophylaxis and treatment to minimize
      severity in cases of recurrence are discussed in the article, using reproductive
      transitional events as markers.

PMID- 11995803
TI  - Autoantigens and Sjogren syndrome.
AB  - PURPOSE: To review recent experimental evidence on the involvement of
      autoantigens and autoantibodies in the pathogenesis of organ-specific
      autoimmunity in Sjogren syndrome (SS). METHODS: Among candidate autoantigens in
      SS, we investigated the role of alpha-fodrin in the lacrimal gland using a mouse
      model and a lacrimal gland cell line established in p53 knockout mice. We also
      tried to identify a novel organ-specific autoantigen by screening the human
      salivary gland cell line (HSG) against sera from SS patients. The specificity and
      sensitivity of this autoantigen to SS patient sera, its cellular localization,
      and the gene encoding the protein were analyzed. RESULTS: In addition to the
      previously identified 120-kd alpha-fodrin in the salivary gland, a shorter
      fragment was detected, indicating that there may be a distinct apoptosis-related
      protease that cleaves alpha-fodrin in the lacrimal gland. A novel salivary gland
      specific autoantibody was detected in 50.9% of sera from SS patients. The antigen
      recognized by this antibody may be a 45-kd nucleus protein not recognized in its
      native form. CONCLUSION: The precise roles of autoantigens in organ-specific
      autoimmunity are still unclear, although accumulated evidence suggests that they
      may be associated with disease progression. Further studies of alpha-fodrin and
      the 45-kd antigen may contribute to the understanding of the pathogenesis of SS
      and may provide a new strategy for organ-specific therapy, such as vaccination
      with analogue peptides.

PMID- 11995804
TI  - Significance of mucin on the ocular surface.
AB  - PURPOSE: To review the significance of mucin in the tear film and the ocular
      surface epithelium. METHODS: Summary of the information on how mucin derived from
      the corneal and conjunctival epithelia and from goblet cells plays a role in the
      stability of the tear film over the ocular surface. The change in mucin
      expression derived from the ocular surface epithelium is also discussed with
      reference to ocular surface disease. RESULTS: The corneal and conjunctival
      epithelia produce transmembrane mucins such as MUC1, MUC2, and MUC4. In contrast,
      goblet cells produce the gel-forming secretory mucin, MUC5AC. The lacrimal gland
      produces MUC7. On the ocular surface, cooperation between transmembrane mucin and
      secretory mucin is necessary for the stability of the tear film. The expression
      of mucin from the ocular surface epithelium is coordinated from the time of
      eyelid opening and is altered in conditions such as squamous metaplasia and dry
      eye. This alteration may result in instability of the tear film. CONCLU SION: The
      induction of mucin from the ocular surface may facilitate the stability of the
      tear film, and increased knowledge may lead to the development of a new modality
      for the treatment of dry eye.

PMID- 11995805
TI  - Breakdown of chromosomal DNA.
AB  - The human genome contains 30,000 to 50,000 genes. Much is known regarding the
      structure, regulation, and replication of genes in animal cells. In addition, the
      mechanisms by which DNA is degraded have been elucidated in recent years. DNA is
      degraded under certain circumstances, in particular, during apoptotic cell death.
      Some mammalian cells, such as mature erythrocytes and cells in the lens of the
      eye, lose their nuclei during differentiation. In this article, the molecular
      mechanism of the apoptotic DNA degradation and the enucleation process of
      erythroid cells are discussed.

PMID- 11995806
TI  - Epithelial repair: roles of extracellular matrix.
AB  - PURPOSE: To review studies of the roles of extracellular matrix (ECM) metabolism
      in corneal epithelium during wound repair. Methods. 1) Alterations in the
      structure and composition of epithelial basement membrane during corneal
      epithelial healing were examined histologically and immunohistochemically. 2) The
      effects of procollagen and hyaluronan synthesis inhibitors on the spread of
      rabbit corneal epithelium were determined in organ culture. 3) Expression of
      keratan sulfate proteoglycan (KSPG) proteins in corneal epithelium was examined
      during repair after injury in wild-type and lumican-null mice. RESULTS: 1)
      Corneal epithelial basement membrane was transiently degraded and reassembled
      during tissue repair. Patterns of type IV collagen immunoreactivity were also
      transiently altered. The system of matrix metalloproteinase-tissue inhibitors of
      metalloproteinases may play an important role in the disassembly and
      reorganization of epithelial basement membrane. 2) Inhibitors of procollagen
      secretion and hyaluronan biosynthesis disrupted the spread of a corneal
      epithelial sheet in situ. 3) Among the corneal KSPG proteins examined, lumican
      was transiently expressed in migrating murine corneal epithelial cells. Anti
      lumican antibody inhibited corneal epithelial resurfacing in organ culture. The
      absence of lumican was found to delay corneal epithelial wound healing in mice.
      CONCLUSION: Extracellular matrix metabolism by the injured corneal epithelium is
      important in the repair process.

PMID- 11995807
TI  - Role of Fas ligand in ocular tissue.
AB  - The expression of Fas ligand (FasL) in the eye is an important factor in the
      maintenance of immune privilege. Although FasL expression in donor corneas
      contributes to prolonged survival of orthotopic corneal allografts in solid organ
      transplantation, FasL gene-transfected tissues reportedly lead to graft
      destruction through neutrophil recruitment. Differences in the effects of FasL
      have been attributed to different roles of soluble FasL (sFasL) and membrane FasL
      (mFasL). This is based on the presumption that the signals through sFasL and
      mFasL differ, with one causing apoptosis and the other activating inflammation.
      It was recently reported that inflammation caused by FasL was inhibited at an
      immune-privileged site, and therefore the effects of FasL may depend on
      differences in the anatomic sites where FasL-expressing cells are located. In
      this article, we discuss the role of sFasL and mFasL in ocular immune privilege.

PMID- 11995808
TI  - Ocular immune privilege and CD1d-reactive natural killer T cells.
AB  - PURPOSE: Immune privilege in the eye is, in part, associated with the development
      of an antigen-specific systemic tolerance termed anterior chamber-associated
      immune deviation (ACAID). Natural killer T (NKT) cells express T-cell receptor
      and natural killer (NK) markers and are classified as innate immune cells partly
      because they produce cytokines within minutes of signals. The aim of this study
      was to elucidate the role of murine NKT cells in the induction of T regulatory
      cells in anterior chamber-associated immune deviation. METHODS: Anterior chamber
      associated immune deviation T regulatory cell generation ability was examined in
      the following NKT cell-deficient mice: SJL mice, CDld or Jalpha281 knockout (KO)
      mice on C57BL/6 (B6) background, and NKT cell-depleted mice. To detect T
      regulatory cells, splenic T cells were harvested 7 days after anterior chamber
      inoculation of ovalbumin (50 microg/2 microL in Hanks balanced salt solution
      [HBSS]), mixed with ovalbumin-primed T cells (effector) and ovalbumin-pulsed
      antigen-presenting cells (stimulator), and then cotransferred into the ear pinnae
      of a syngeneic naive mouse (local adoptive transfer assay). Ear swelling was
      measured 24 hours later. RESULTS: Anterior chamber-inoculated B6 mice developed T
      regulatory cells, but all natural killer T cell-deficient mice did not generate T
      regulatory cells unless they were reconstituted with natural killer T cells. We
      also found that the number of splenic natural killer T cells were increased in
      anterior chamber-inoculated B6 mice and those natural killer T cells produced IL
      10. CONCLUSIONS: CD1d-reactive natural killer T cells are essential for the
      induction of T regulatory cells in anterior chamber-associated immune deviation
      through their IL-10 production and are involved in the maintenance of immune
      privilege of the eye.

PMID- 11995809
TI  - Respiratory syncytial virus may be a pathogen in allergic conjunctivitis.
AB  - PURPOSE: The host response to allergens appears to be regulated by T helper type
      2 cell patterns of local cytokine production. We hypothesized that respiratory
      syncytial virus (RSV) infects the normal conjunctival epithelium and produces
      interleukin (IL)-4, causing a local allergic reaction. METHODS: Giemsa staining,
      immunocytochemical study, flow cytometric analysis, and reverse-transcriptase
      polymerase chain reaction (RT-PCR) were performed on tear and cytology samples
      from individuals with allergic and postoperative conjunctivitis. Histamine was
      assayed by radioimmunoassay, and IL-4 by enzyme-linked immunosorbent assay.
      RESULTS: The total number of cells collected by brush cytology did not differ
      between allergic and postoperative conjunctivitis. The levels of IL-4 and
      histamine in the specimens and mean IL-4 tear level were significantly increased
      in patients with allergic conjunctivitis. Cytocentrifuge preparations contained
      conjunctival epithelial cells with lymphocytes (a few CD3- and CD4-bearing
      cells), mast cells, eosinophils, and higher human leukocyte antigen (HLA)-DR
      expression in allergic patients. RT-PCR analysis showed that samples from
      allergic conjunctivitis expressed increased transcripts of IL-4 and IL-13. A
      higher percentage of RSV sequences were detected in allergic patient samples.
      Immunocytochemical study and RT-PCR showed that epithelial cells were infected
      with RSV. Average concentrations of IL-4 in culture supernatants were higher than
      levels in uninfected cells. CONCLUSIONS: These results suggest that the clinical
      features of human allergic conjunctivitis are associated with T helper type 2
      cytokine expression. RSV in conjunctival epithelial cells may be an environmental
      pathogen in allergic conjunctivitis.

PMID- 11995810
TI  - Effects of combination chemotherapy with biscoclaurine-derived alkaloid
      (Cepharanthine) and nimustine hydrochloride on malignant glioma cell lines.
AB  - In the treatment of malignant glioma, chemotherapy plays a critical role as do
      surgical resection and irradiation. Cepharanthine (CEP), a biscoclaurine-derived
      alkaloid, reportedly potentiates the effects of antitumor agents and induces
      apoptosis in some cancer cells. Here, we examined the effects of CEP, alone and
      in combination with nimustine hydrochloride (ACNU), on the in vitro proliferation
      of malignant glioma cells. The cell lines used were U87MG, U251MG, and T98G. At
      concentrations from 1 to 10 microg/ml, CEP-promoted cell proliferation somewhat;
      growth inhibition was noted at concentrations of 15 microg/ml and higher. Phase
      contrast microscopy showed that cells tended to detach from the culture dishes
      and that cell density became sparse at the higher concentrations. DAPI
      fluorescence nuclear staining revealed condensation and fragmentation of nuclei,
      indicating the induction of apoptosis. To examine the cascade of apoptosis, the
      caspase inhibitors YVAD and DEVD were added. They inhibited CEP-induced apoptosis
      in U251MG cells (a p53-mutant cell line), but not in U87MG cells (a p53 wild-type
      cell line), suggesting that in CEP-induced apoptosis two possible cascades are in
      play. In combination with ACNU, the effects of the higher concentrations of CEP
      were enhanced.

PMID- 11995811
TI  - Mitogen activated protein kinase activation and oxidant signaling in astrocytoma
      cells.
AB  - Presence of increased reactive oxygen species (ROS) has been observed in most
      high risk factors for brain tumor development. Our past study demonstrated that
      ROS could induce increased brain tumor cell proliferation. Growth effects of ROS
      may involve modifications of cellular proteins such as mitogen-activated protein
      kinases (MAPKs), which regulate cell proliferation. Here, we report effects of a
      ROS (hydrogen peroxide, H2O2) and an antioxidant (N-acetylcysteine, NAC) on MAPK
      activation in astrocytoma (U373-MG) cells. MAPKs are activated by phosphorylation
      that can be detected by Western blot analysis. The unphosphorylated/inactivated
      form of MAPK exhibits slower mobility on SDS-PAGE compared to the
      phosphorylated/activated form. Densitometric analysis was used to measure MAPK
      activation. Results indicate that H2O2 caused a dose and time-dependent increase
      in MAPK activation in astrocytoma cells. Furthermore, ROS-induced activation was
      almost completely suppressed by NAC. NAC also inhibited serum-induced MAPK
      activation indicating there may be an oxidant-sensitive component to serum
      induced growth signaling. Modifications of MAPKs by H2O2 demonstrate that ROS
      induced proliferation is via biochemical pathways similar to other known growth
      stimuli. Understanding of processes that link a proliferation signal (ROS) to
      cell proliferation can aid in the selection of therapy used to suppress brain
      tumor growth.

PMID- 11995812
TI  - Evaluation of radiofrequency ablation as an alternative for the treatment of
      brain tumor in rabbits.
AB  - Radiofrequency ablation (RFA) has emerged recently as a promising therapy for
      extracranial malignancies. This experiment was conducted to explore the potential
      of RFA for the treatment of brain tumor in a rabbit model with imaging
      histological assessment. Eighteen rabbits with intracranially implanted VX2
      tumors of 0.9+/-0.2 cm in diameter were divided into two groups. Group A (n = 12)
      was treated with a cooled-tip RFA technique at 30 watts for 30-60 s. Group B (n =
      6) received sham operation. The therapeutic efficacy was evaluated by comparing
      survival rate, magnetic resonance imaging (MRI) and histological findings. All
      animals in Group B died within one month after tumor implantation (19+/-2.6
      days). Tumor eradication was achieved in 6/12 rabbits (50.0%) in Group A, of
      which three rabbits survived longer than three months, another three rabbits were
      found free of viable tumor when sacrificed. Five rabbits suffered from local
      tumor relapse. One rabbit developed intracranial metastasis to the brain stem
      despite a complete ablation of the original tumor. Three-month survival rate of
      RFA treated rabbits was significantly higher (p < 0.05) than that of control
      rabbits. The typical MRI appearances of the acute RFA lesion consisted of three
      characteristic concentric zones, which corresponded to central coagulative
      tissues (Zone A), peripheral hemorrhagic rim (Zone B) and interstitial edema
      (Zone C) on histology. This study suggests that RFA may become a promising
      alternative therapy for the treatment of brain tumor. The recognized characters
      of thermal lesion on MRI and histology may prove valuable in delimitating the
      ablation range and understanding the biological response of the RFA.

PMID- 11995813
TI  - Ki-67 labeling is correlated with the time to recurrence in primary
      glioblastomas.
AB  - The Ki-67 labeling index (LI) was shown in many cut-off studies to be
      significantly correlated to the postoperative survival probability in gliomas in
      univariate and multivariate analyses. However, a direct relationship of the Ki-67
      LI and the growth fraction, respectively, to clinical growth parameters was not
      demonstrated in a single tumor type of this group until now. We compared the Ki
      67 LI of 20 primary glioblastomas and their recurrent tumors with the time to
      reoperation for recurrence. Regression analyses showed (1) a high reproducibility
      of the LIs at the second versus the first operation corresponding to an inherent
      growth potential of a given individual tumor and (2) a strong inverse correlation
      of LI to time to recurrence (TR) (r = -0.92). Additionally to a lower LI
      (corresponding to a smaller growth fraction), a longer cycle time could be
      derived in slowly growing as compared to rapidly growing tumors. A direct
      relationship of the Ki-67 LI to a clinical time parameter (the TR) was obtained,
      and a predictive significance of individual LIs in glioblastomas could be
      defined.

PMID- 11995814
TI  - Lovastatin is a potent inhibitor of meningioma cell proliferation: evidence for
      inhibition of a mitogen associated protein kinase.
AB  - Lovastatin inhibits 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase the
      rate limiting enzyme for synthesis of mevalonic acid, a precursor for
      cholesterol, farnesyl and geranylgeranyl pyrophosphate isoprenoids. Recent
      studies suggest it also has growth inhibitory properties. Posttranslational
      farnesyl or geranylgeranylation of low molecular weight GTP-binding proteins such
      as RAS and RHO are thought to be an essential step in activation of
      phosphorylation cascades such as the RAS-RAF-1-MEK-1-MAPK/ERK pathway which
      stimulate cell proliferation. In this study, we evaluated lovastatin effects on
      meningioma cell proliferation and activation of the MEK-1-MAPK/ERK pathway. The
      effect of lovastatin on cell proliferation was assessed in eight human meningioma
      cell cultures stimulated by platelet derived growth factor (PDGF)-BB,
      cerebrospinal fluid (CSF), and fetal bovine serum (FBS). Concomitant lovastatin
      effects on phosphorylation/activation of mitogen-activated protein
      kinase/extracellular signal regulated kinase (MAPK/ERK) kinase (MEK-1) and
      MAPK/ERK were assessed by Western blot. Whether lovastatin acts via a mevalonate
      dependent mechanism was also evaluated. Coadministration of lovastatin completely
      blocked PDGF-BB, CSF, and FBS stimulation of [3H]-thymidine incorporation and
      cell proliferation. Lovastatin inhibited PDGF-BB's stimulatory effect in a dose
      dependent manner. Concomitant with its growth inhibitory effects, lovastatin
      reduced phosphorylation/activation of MEK-1/2 in five meningiomas and MAPK/ERK in
      seven. Coadministration of mevalonate with lovastatin partially restored PDGF's
      mitogenic effect. Lovastatin is a potent inhibitor of meningioma cell
      proliferation which may act in part by reducing activation of MEK-1-MAPK/ERK
      pathway. Additional studies are warranted to assess whether lovastatin and
      similar HMG-CoA reductase inhibitors represent a new adjunctive chemotherapy for
      recurrent meningiomas.

PMID- 11995815
TI  - The antimicrotubule drug estramustine but not irradiation induces apoptosis in
      malignant glioma involving AKT and caspase pathways.
AB  - Irradiation is one of the cornerstones used in the treatment of malignant glioma.
      However, the effect is modest and glioma cells generally display a pronounced
      radio-resistance. In this study, the effect of irradiation, alone and in
      combination with the antimicrotubule drug estramustine (EaM), was investigated in
      vitro using the BT4C rat glioma cell line, and in vivo the BT4C rat intracerebral
      glioma model was used. Apoptosis was detected by analysing DNA laddering, in situ
      end labelling (ISEL) and Annexin V reactivity. In addition, phosphorylation
      status of MAPK, JNK, p38, and AKT, proteins involved in pro- and anti-apoptotic
      signalling pathways was analysed by Western blotting. Irradiation did not induce
      apoptosis, neither in vitro nor in vivo. EaM, however, induced apoptosis in vivo
      and in vitro, regardless of whether EaM was given alone, before or after
      irradiation. When BT4C cells were treated with the caspase-3 inhibitor Ac-DEVD
      CHO prior to EaM, the number of apoptotic cells was decreased, indicating an
      involvement of caspase-3. The signalling pathways regulating apoptosis are
      complex and involve kinases such as MAPK, JNK, p38 and AKT. Irradiation did not
      induce any changes in the expression levels or phosphorylation status of these
      proteins. On the other hand, the phosphorylation level of AKT was reduced after
      EaM treatment, which might, in part, propose how EaM induces apoptosis in glioma
      cells.

PMID- 11995816
TI  - Proteases and the biology of glioma invasion.
AB  - Despite optimal clinical treatment, the prognosis for malignant gliomas remains
      poor. One of the primary reasons for treatment failure is not diffuse
      dissemination, but local invasion. Recently, there has been an increase in
      information regarding specific molecules that determine the aggressiveness and
      invasion potential of high-grade astrocytic tumors. In particular, expression of
      matrix metalloproteases in high-grade gliomas appears to correlate with tissue
      invasiveness. It is the purpose of the present review to describe the connection
      between alterations in growth-related genes, protease activity, and tumor
      biology, and how these connections may suggest potential novel therapeutic
      targets.

PMID- 11995817
TI  - Chromosome instability in malignant astrocytic tumors detected by fluorescence in
      situ hybridization.
AB  - Malignant tumors intrinsically manifest genetic instability, and consequently
      genetic aberrations successively accumulate in tumor cells as the tumor
      progresses. However, the relationship of genetic instability and biological
      behavior still remains to be investigated in malignant tumors. In the present
      investigation, the relationship between chromosomal instability and patient
      prognosis was studied in 19 malignant gliomas. Chromosomal instability was
      estimated by numerical variation in chromosomes 7, 10 and 17 which was measured
      by fluorescence in situ hybridization (FISH), and DNA ploidy was determined by
      laser scanning cytometry. The mean number of fractions was significantly higher
      in cases with DNA aneuploidy than in those with DNA diploidy. The tendency toward
      higher fractions in glioblastomas existed, although it did not reach statistical
      significance. Kaplan-Meier survival rate analysis demonstrated significantly
      lower survival rates in patients with higher fractions of chromosome 7 (>5) than
      others. Our results suggest that DNA aneuploidy in malignant gliomas reflects an
      underlying chromosomal instability, and that this instability is associated with
      clinical behavior.

PMID- 11995818
TI  - Local interstitial chemotherapy with sustained release bucladesine in de novo
      glioblastoma multiforme: a preliminary study.
AB  - This clinical study was designed to evaluate the safety and efficacy of the
      sustained release form of dibutryl adenosine-3',5'-cyclic monophosphate (dB-cAMP,
      bucladesine) placed in the tumor resection cavity at the time of recurrence of
      the de novo glioblastoma multiforme (GBM) patients. In a randomized prospective
      manner, 40 patients who were diagnosed as GBM in their first operations were
      included in this study. Four different therapy protocols were used: First group
      of 10 patients had tumor resection only. Second group assessed had only systemic
      chemotherapy as six i.v. infusions of fotemustine after tumor resection. Third
      group had implantation of bucladesine-loaded biodegradable polymeric sustained
      release (bcl-SR) pellets while the last group received six i.v. infusions of
      systemic fotemustine as in the second group in addition to local implantation of
      bcl-SR pellets. A biodegradable polymer, poly-DL-lactide-co-glycolide with
      molecular weight of 80000, was used as carrier matrix for the drug with an
      approximately 4-5 months of release time. Maximal doses of 20 mg of bucladesine
      with a mean dose of 15.5 mg were implanted. No bone marrow suppression occurred
      and there were no wound infections as far as the local bucladesine-loaded polymer
      therapy is concerned. In this randomized prospective trial of local interstitial
      chemotherapy with long acting bcl-SR did show a statistically significant delay
      of recurrence on the treatment of GBM patients. Best treatment results obtained
      from the local bcl-SR + systemic fotemustine treated group in which survival rate
      estimated by the Kaplan-Meier method was 70% in de novo GBM at 12 months.

PMID- 11995819
TI  - Imaging changes after stereotactic radiosurgery of primary and secondary
      malignant brain tumors.
AB  - After radiosurgery of malignant tumors, it can be difficult to discriminate
      between transient treatment effects, radiation necrosis, and tumor progression on
      post-treatment imaging. Misinterpretation of an enlarging lesion may lead to
      inappropriate treatment and contribute to disagreements about treatment efficacy.
      In an effort to clarify this problem, we reviewed our experience with
      interpreting post-radiosurgical imaging in patients with malignant primary and
      secondary brain tumors. We reviewed results of radiosurgery of 30 malignant
      gliomas and 35 metastatic brain tumors with minimum follow up of 1 year or until
      death. Of 30 gliomas, 73% were larger a mean of 13 weeks after radiosurgery. Of
      35 metatstatic tumors, 22% were larger a mean of 10 weeks after radiosurgery.
      Eleven had 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) of
      enlarging lesions. Eight showed increased activity with respect to brain; three
      decreased activity. Of the eight, six predicted incorrectly based upon the
      patients' subsequent courses (all alive, mean follow up of 27 months), and two
      correctly, with the patients dying from the imaged lesions 8 and 13 months later.
      Of the three with FDG uptake less than brain, one patient was alive with 32 weeks
      of follow up, and two patients died from the imaged lesion 13 and 21 months
      later. Radiographic enlargement after radiosurgery is common, especially for
      gliomas. Physicians caring for these patients should be aware of this phenomenon
      and be cautious in interpreting post-treatment images. MRI appearance may be
      useful for metastases. FDG-PET seems unreliable. Further evaluation of Tl-201 and
      HMPAO SPECT or MRS is warranted.

PMID- 11995820
TI  - Salvage chemotherapy with CPT-11 for recurrent glioblastoma multiforme.
AB  - BACKGROUND: A prospective Phase II study of CPT-11 in adult patients with
      recurrent supratentorial glioblastoma multiforme (GBM). METHODS: Forty patients
      (25 men, 15 women) ages 32-71 years (median 59), with recurrent GBM were treated.
      All patients had previously been treated with surgery and involved field
      radiotherapy (median dose 60 Gy; range 59-60). Additionally, all patients were
      treated with adjuvant chemotherapy (BCNU in 20, PCV in 18, Procarbazine in 2).
      Twenty-five patients (62%) were on anticonvulsants (phenytoin in 15,
      carbamazepine in 10) and 26 patients (65%) were on dexamethasone. Recurrent
      disease was defined by neuroradiographic disease progression (>25% increase in
      tumor dimensions) using gadolinium-enhanced MR imaging. The starting dose of CPT
      11 was 400 mg/m2 followed in three weeks by 500 mg/m2, operationally defined as
      one cycle. At week 6, all patients were evaluated with MRI and neurological
      examination. RESULTS: All patients were evaluable. Two doses (one cycle) of CPT
      11 were administered to all patients. CPT-11-related toxicity included: diarrhea
      (16 patients, 40%); thrombocytopenia (9 patients, 23%); and neutropenia (6
      patients, 15%). No patient required transfusion nor was treatment for neutropenic
      fever required. No treatment-related deaths were observed. All patients
      demonstrated progressive disease following one cycle of CPT-11. CONCLUSIONS: The
      lack of response to CPT-11 in this patient group with recurrent GBM suggests
      either CPT-11 has minimal activity or CPT-11 doses/schedule utilized in this
      study were sub-optimal. The latter is supported by the modest toxicity seen in
      this study and the previously documented enhanced clearance of CPT-11 in patients
      on anticonvulsants and dexamethasone.

PMID- 11995821
TI  - Utilisation of lignocellulosic wastes for lignin peroxidase production by semi
      solid-state cultures of Phanerochaete chrysosporium.
AB  - In the present work, the production of ligninolytic enzymes by semi-solid-state
      cultures of Phanerochaete chrysosporium BKM-F-1767 (ATCC 24725), employing
      different lignocellulosic wastes as support, was investigated. The waste
      materials employed were grape seeds, wheat straw and wood shavings. Maximum
      lignin peroxidase activities of 1,620 +/- 123 U/l,364 +/- 35 U/l and 571 +/- 42
      U/l were attained, respectively. Nevertheless, low manganese-dependent peroxidase
      activities were found, being insignificant in the grape seed cultures. Moreover,
      the in vivo decolourisation of a model dye compound, the polymeric dye Poly R-478
      (polyvinylamine sulfonate anthrapyridone), by the above-mentioned cultures was
      monitored to assess the degrading capability of the extracellular liquid secreted
      by such cultures. The percentage of biological decolourisation attained by grape
      seed and wood shaving cultures was around 74% and 63%, respectively, whereas it
      was rather low (40%) in the wheat straw ones.

PMID- 11995822
TI  - Degradation of 2,3,4,6-tetrachlorophenol at low temperature and low dioxygen
      concentrations by phylogenetically different groundwater and bioreactor bacteria.
AB  - Effects of low temperature and low oxygen partial pressure on the occurrence and
      activity of 2,3,4,6-tetrachlorophenol degrading bacteria in a boreal chlorophenol
      contaminated groundwater and a full-scale fluidized-bed bioreactor were studied
      using four polychlorophenol degrading bacterial isolates of different
      phylogenetic backgrounds. These included an alpha-proteobacterial Sphingomonas
      sp. strain MT1 isolated from the full-scale bioreactor and three isolates from
      the contaminated groundwater which were identified as beta-proteobacterial
      Herbaspirillum sp. K1, a Gram-positive bacterium with high G + C content
      Nocardioides sp. K44 and an alpha-proteobacterial Sphingomonas sp. K74. The
      Sphingomonas strains K74 and MT1 and Nocardioides sp. K44 degraded 2,4,6
      trichlorophenol and 2,3,4,6-tetrachlorophenol as the sole carbon and energy
      sources. Close to stoichiometric inorganic chloride release with the 2,3,4,6
      tetrachlorophenol removal and the absence of methylation products indicated
      mineralization. Tetrachlorophenol degradation by the Herbaspirillum sp. K1 was
      enhanced by yeast extract, malate, glutamate, pyruvate, peptone and casitone. At
      8 degrees C, Sphingomonas sp. K74 had the highest specific degradation rate
      (mu(max) = 4.9 x 10(-2) mg h(-1) cell(-1)) for 2,3,4,6-tetrachlorophenol. The
      Nocardioides strain K44 had the highest affinity (K(s) = 0.46 mg l(-1))
      fortetrachlorophenol. K1 and MT1 grew microaerophilically in semisolid glucose
      medium. Furthermore, the growth of MT1 was inhibited in liquid glucose medium at
      high oxygen partial pressure indicating sensitivity to accumulating toxic oxygen
      species. On the other hand, trichlorophenol degradation was not affected by
      oxygen concentration (2-21%). The isolates K44, K74 and MT1, with optimum growth
      temperatures between 23 and 25 degrees C, degraded tetrachlorophenol faster at 8
      degrees C than at room temperature indicating distinctly different temperature
      optima for chlorophenol degradation and growth on complex media. These results
      show efficient polychlorophenol degradation by the isolates at the boreal
      groundwater conditions, i.e., at low temperature and low oxygen concentrations.
      Differences in chlorophenol degradation and sensitivities to chlorophenols and
      oxygen among the isolates indicate that the phylogenetically different
      chlorophenol degraders have found different niches in the contaminated
      groundwater and thus potential for contaminant degradation under a variety of
      saturated subsurface conditions.

PMID- 11995823
TI  - Isolation and characterization of a pseudomonas strain that degrades 4
      acetamidophenol and 4-aminophenol.
AB  - Though many microorganisms that are capable of using phenol as sole source of
      carbon have been isolated and characterized, only a few organisms degrading
      substituted phenols have been described to date. In this study, one strain of
      microorganism that is capable of using phenol (3,000 ppm), 4-aminophenol (4,000
      ppm) and 4-acetamidophenol (4,000 ppm) as sole source of carbon and energy was
      isolated and characterized. This strain was obtained by enrichment culture from a
      site contaminated with compounds like 4-acetamidophenol, 4-aminophenol and phenol
      in Pakistan at Bhai Pheru. The contaminated site is able to support large
      bacterial community as indicated by the viable cell counts (2 x 10(4) - 5 x
      10(8)) per gram of soil. Detailed taxonomic studies identified the organisms as
      Pseudomonas species designated as strain STI. The isolate also showed growth on
      other organic compounds like aniline, benzene, benzyl alcohol, benzyl bromide,
      toluene, p-cresol, trichloroethylene and o-xylene. Optimum growth temperature and
      pH were found to be 30 degrees C and 7, respectively, while growth at 4, 25 and
      35 degrees C and at pH 8 and 9 was also observed. Non growing suspended cells of
      strain ST1 degraded 68, 96 and 76.8% of 4-aminophenol (1,000 ppm), phenol (500
      ppm) and 4-acetamidophenol (1,000 ppm), respectively, in 72 hrs. The isolation
      and characterization of Pseudomonas species strain STI, may contribute to efforts
      on phenolic bioremediation, particularly in an environment with very high levels
      of 4-acetamidophenol and 4-aminophenol.

PMID- 11995824
TI  - Biostimulation-based bioremediation of diesel fuel: field demonstration.
AB  - Ex-situ bioremediation of leached cynamonic forest soil at initial diesel oil
      contamination of 6,000 mg kg(-1), 4,000 mg kg(-1) and 2,000 mg kg(-1) was
      investigated after biostimulation with inorganic fertilizers. It was found that
      the added nutrients had no effect on the decontamination of polluted soils. A
      precise and reliable approach for evaluation of the biodegradation process is
      proposed. It comprises application of sensitive and easily accessible diagnostic
      parameters and relations, calculated on the basis of n-alkanes and isoprenoids-
      pristane (2.6.10.14-tetramethylpentadecane, i-C19H40) and phytane (2.6.10.14
      tetramethylhexadecane, i-C20H42) distribution.

PMID- 11995825
TI  - Isobutylidenediurea degradation by Rhodococcus erythropolis.
AB  - A new enzyme (isobutylidenediurea amidinohydrolase) catalyzing the hydrolysis of
      isobutylidenediurea (a condensation product of urea and isobutyraldehyde widely
      used as a slow-release nitrogeneous fertilizer) was characterized from a strain
      of Rhodococcus erythropolis. The enzyme was purified 1,250-fold to apparent
      homogeneity and shown to hydrolyze the fertilizer to urea and isobutyraldehyde at
      a molar ratio of 2: 1. No activity was observed with ureido- or other
      structurally related compounds. Its molecular mass was determined by native
      polyacrylamide gelelectrophoresis and matrix-assisted laser desorption/ionisation
      time-of-flight mass spectrometry to be 15 kDa (+/-2 kDa) and 16.4 kDa,
      respectively. Growth of the bacterium in the presence of isobutylidenediurea led
      to an increased expression of the constitutively synthetized enzyme.

PMID- 11995826
TI  - Bioremediation of diesel-contaminated soils: evaluation of potential in situ
      techniques by study of bacterial degradation.
AB  - The development of a simple laboratory methodology allows the implementation of
      in situ bioremediation of polluted soils with diesel fuel. In this investigation
      microbiological and chemical analyses and a suitable bioreactor design, were very
      useful for suggesting the best ways to improve biodegradation extents in a diesel
      enriched soil. Biostimulation with inorganic nitrogen and phosphorus produced the
      best results in a simple bioreactor, with biodegradation extents higher than 90%
      after 45 days. Also, the addition of activated sludge from a domestic wastewater
      plant increased the degradation rate to a great extent. In both cases,
      microbiological studies showed the presence of Acinetobacter sp. degrading most
      of the hydrocarbons. Simultaneously, a diesel fuel release (approximately 400,000
      l) was studied. Samples taken in polluted soil and water revealed that bacteria
      from the genus Acinetobacter were predominant. In plate studies, Acinetobacter
      colonies produced a whitish substance with the characteristics of a
      biosurfactant. Remarkably, the presence of this product was evident at the field
      site, both in the riverbanks and in the physical recovery plant. The study of the
      similarities between laboratory results and the diesel spill site strongly
      suggested that natural conditions at the field site allowed the implementation of
      in situ bioremediation after physical removal of LNAPL (light nonaqueous-phase
      liquids).

PMID- 11995827
TI  - Product distribution during transformation of multiple contaminants by a high
      rate, tetrachlorethene-dechlorinating enrichment culture.
AB  - Radiolabeled tetrachloroethene (PCE) and carbon tetrachloride (CT) were added to
      batch systems containing a lactate-enrichment culture displaying apparent
      dehalorespiration abilities to analyze the influence of mixtures on product
      distribution. Both CT and PCE were readily dechlorinated, although significant
      carbon disulfide (CS2) formation was observed during CT transformation.
      Calculated 1,2-14C-PCE recoveries for biotic treatments were between 91 and 104%,
      but an inability to recover products such as CS2 led to lower recoveries of 14C
      CT (55 to 62%). While the majority of activity in 14C-CT-spiked treatments was
      recovered in the volatile fraction, 14CO2 increased significantly over time. 1,2
      14C-PCE was primarily recovered in volatile and non-strippable fractions, but a
      significant increase in 14CO2 relative to cell-free controls suggested that the
      presence of a non-specific dechlorination pathway complementing
      dehalorespiration. The addition of both CT and PCE inhibited the transformation
      of the individual compounds and reduced the percentages recovered as 14CO2.
      However, the magnitude of these reductions was not severe and appeared to be the
      result of slower overall transformation rather than a complete inhibition of
      mineralization pathways.

PMID- 11995828
TI  - Optimal operational factors for nitrite accumulation in batch reactors.
AB  - The environmental factors that affected the accumulation of nitrite in nitrifying
      reactors were investigated using a mixed culture. A batch reactor with 50 mg-N/l
      of ammonia was used. The pH, temperature and dissolved oxygen concentration were
      varied. The concentration of unionized free ammonia also changed with the
      oxidation of ammonia and the variation of pH and temperature. The accumulation of
      nitrite was affected sensitively by pH and temperature. A higher nitrite
      concentration was observed at pH 8-9 or temperature around 30 degrees C. The
      dissolved oxygen also affected, giving the highest nitrite accumulation at around
      1.5 mg/l. These were the favored conditions for nitrite production. The free
      ammonia concentration influenced the nitrite accumulation also, by inhibiting
      nitrite oxidation. The inhibition became apparent at a concentration of
      approximately 4 mg/l or above, but insignificant at below 1 mg/l. Thus,
      simultaneously high free ammonia concentration and maximum specific ammonia
      oxidation rate (above 15 x 10(-3) mg-N/mg-VSS x h) were needed for a significant
      nitrite accumulation. When the two conditions were met, then the highest
      accumulation was observed when the ratio of the maximum specific oxidation rate
      of ammonia to the maximum specific oxidation rate of nitrite (ka/kn) was highest.
      Under the optimal operating conditions of pH 8, 30 degrees C and 1.5 mg/l of
      dissolved oxygen, as much as 77% of the removed ammonia accumulated in nitrite.

PMID- 11995829
TI  - Converging catabolism of 2,4,6-trinitrophenol (picric acid) and 2,4-dinitrophenol
      by Nocardioides simplex FJ2-1A.
AB  - Initial F420-dependent hydrogenation of 2,4,6-trinitrophenol (picric acid)
      generated the hydride sigma-complex of picrate and finally the dihydride complex.
      With 2,4-dinitrophenol the hydride sigma-complex of 2,4-dinitrophenol is
      generated. The hydride transferring enzyme system showed activity against several
      substituted 2,4-dinitrophenols but not with mononitrophenols. A Km-value of 0.06
      mM of the hydride transfer for picrate as substrate was found. The pH optima of
      the NADPH-dependent F420 reductase and for the hydride transferase were 5.5 and
      7.5, respectively. An enzymatic activity has been identified catalyzing the
      release of stoichometric amounts of 1 mol nitrite from 1 mol of the dihydride
      sigma-complex of picrate. This complex was synthesized by chemical reduction of
      picrate and characterized by 1H and 13C NMR spectroscopy. The hydride sigma
      complex of 2,4-dinitrophenol has been identified as the denitration product. The
      nitrite-eliminating activity was enriched and clearly separated from the hydride
      transferring enzyme system by FPLC. 2,4-Dinitrophenol has been disproven as a
      metabolite of picrate (Ebert et al. 1999) and a convergent catabolic pathway for
      picrate and 2,4-dinitrophenol with the hydride sigma-complex of 2,4-dinitrophenol
      as the common intermediate has been demonstrated.

PMID- 11995830
TI  - Effects of hyaluronic acid on postoperative adhesion of tendo calcaneus surgery:
      an experimental study in rats.
AB  - Adhesions are a significant problem after tendon surgery. The effects of
      hyaluronic acid on adhesion formation of the tendo calcaneus were investigated in
      this study. Twenty Wistar rats were utilized. Both tendo calcanei were incised
      transversely, and then repaired. Hyaluronic acid (0.2 cc) was injected into
      peritendinous tissue on the right side, while the same amount of normal saline
      was injected to the left side as a control. The animals were sacrificed 40days
      after the experiment. Both the right and left tendon adhesions were evaluated
      both macroscopically and microscopically for the presence of adhesions (grading
      scale 0-4). Throughout the experimental period, there was no difference in range
      of motion of the ankle between the two groups. Macroscopically, there were fewer
      adhesions in the experimental group (mean 0.6 +/- 0.8) compared to the controls
      (mean 1.1 +/- 0.2). This difference was not statistically significant (p = .096).
      Histopathologically, these parameters were similar in both the experimental (mean
      1.15 +/- 0.98) and the control groups (mean 1.9 +/- 1.25). This difference was
      significant (p = .043). Hyaluronic acid may be effective for prevention of
      adhesions in the tendo calcaneus though this effect could not be demonstrated
      experimentally.

PMID- 11995831
TI  - Acute digital ischemia in infants: the hair-thread tourniquet syndrome--a report
      of two cases.
AB  - Infants are susceptible to digital ischemia if a toe is encircled by a strand of
      hair on some other similar material. Infants under 6 months are particularly at
      risk. There is often a delay of 3-4 days before the condition is recognized.
      Prompt removal is necessary in order to prevent loss of the part. This syndrome
      is referred to as the hair-thread tourniquet syndrome. Two cases illustrating the
      presenting clinical findings and the operative treatment are presented.

PMID- 11995832
TI  - Pedal plexiform neurofibroma: review of the literature and case report.
AB  - Plexiform neurofibroma typically occurs in the setting of neurofibromatosis type
      1, and is included in the diagnostic criteria for neurofibromatosis. Plexiform
      neurofibromas generally affect larger peripheral nerves and are uncommon in the
      foot and ankle. While there are several reports of large neurofibromas involving
      the foot, they have been described on the plantar aspect. We report the first
      known case of plexiform neurofibroma involving the deep peroneal nerve of the
      foot. A review of the literature is also presented.

PMID- 11995833
TI  - Traumatic hallux valgus following rupture of the medial collateral ligament of
      the first metatarsophalangeal joint: a case report.
AB  - Metatarsophalangealjoint injuries of the great toe are receiving increasing
      attention in athletes. Significant disability and long-term morbidity can result
      from these focal injuries. The entity known as turf-toe is widely recognized.
      Rupture of the medial collateral ligament of the first metatarsophalangeal joint
      is less common. A case of traumatic rupture of the medial collateral ligament in
      the great toe of a soccer player, which progressed to hallux valgus deformity, is
      presented.

PMID- 11995834
TI  - Bilateral coexistent calcaneonavicular and talocalcaneal tarsal coalition: a case
      report.
AB  - Tarsal coalition refers to a union of two or more tarsal bones. The union may be
      fibrous, cartilaginous, or bony. The most common sites of tarsal coalition
      reported in the literature are the calcaneonavicular, the talocalcaneal, and,
      less commonly, the talonavicular areas. Bilateral coexistent multiple tarsal
      coalitions are a rare occurrence. The authors present a case report of a 17-year
      old boy with bilateral coexistent calcaneonavicular and talonavicular bars. The
      diagnosis was established by radiographs and CT scanning. The patient was treated
      conservatively with immobilization of the foot in a below-knee walking plaster
      cast followed by the use of an orthosis with a lateral iron and a medial T strap.
      The patient was pain-free at 2-year follow-up.

PMID- 11995835
TI  - Posterior calcaneal displacement osteotomy with lateral wall reduction.

PMID- 11995836
TI  - Plantar plate ruptures of the second metatarsophalangeal joint.

PMID- 11995837
TI  - Are you experienced?

PMID- 11995838
TI  - Mosaicplasty of the talus: a joint contact analysis in a cadaver model.
AB  - Treating large osteochondral defects of the talar dome is a challenging problem
      for the foot and ankle surgeon. The purpose of this study was to determine if
      ankle joint surface mechanics can be restored by repairing large osteochondral
      defects with multiple osteochondral cylinder grafts. Pressure-sensitive film was
      used to measure total contact area and mean contact pressure of the ankle joint
      using a cadaver foot model. Specimens were sequentially tested evaluating the
      following conditions: 1) intact ankle, 2) with osteochondral defect, and 3) after
      mosaicplasty. An ovoid chondral defect measuring 8 x 12 mm for each specimen was
      consistently placed within the center of the contact zone. Multiple osteochondral
      grafts were harvested from donor tali and placed in the defect. Two graft arrays
      arranged in either a cluster of four 4 x 10 mm or two 6 x 10 mm plugs were
      inserted sequentially to fill the defect and were tested separately. Specimens
      were positioned in a neutral alignment on a custom load frame and axially loaded
      to 560 N with the pressure transducer in place. The transducers were then
      digitized and analyzed with an imaging software program. Data for total contact
      area and mean contact pressures for all conditions of each specimen were
      collected and statistically analyzed. Results demonstrated that the 6-mm grafts
      were less than optimal in fully restoring the defect in the contact zone of the
      talus. There was significant decrease in mean total contact area and increase in
      contact zone mean pressure compared to the intact condition (p < .05). Whereas, 4
      mm plugs nearly restored joint contact area and pressure to normal levels. These
      findings suggest that focal talar dome defects can be repaired to restore normal
      ankle contact characteristics via the placement of small, osteochondral
      cylindrical grafts of talar origin.

PMID- 11995839
TI  - A prospective comparison of clinical, radiographic, and intraoperative features
      of hallux rigidus.
AB  - Forty-four patients (47 feet) underwent surgical intervention for symptomatic
      hallux rigidus between February 1998 and April 1999. Each foot was initially
      graded according to a four-stage hybrid hallux rigidus radiographic grading
      system. A subjective evaluation based on a modified American Orthopaedic Foot and
      Ankle Surgery clinical rating system was performed. An objective physical
      examination was performed. Angular and linear measurements were obtained from
      standard weightbearing radiographs. The extent of articular derangement for the
      first metatarsal head, base of the proximal phalanx, and tibial and fibular
      sesamoids were graded according to the American Orthopaedic Foot and Ankle
      Society intraoperative grading system. Finally, a means of quantifying the
      percentage of first metatarsal head articular derangement was performed.
      Significant differences were identified between joints radiographically
      classified as grade II, which had lower nonweightbearing, relaxed hanging
      position (p = .041); nonweightbearing assisted dorsiflexion (p = .000); actual
      nonweightbearing dorsal range of motion (p = .002); and actual plantar range of
      motion (p = .009) than those classified as grade I. The angle of deviation of the
      second metatarsophalangeal joint revealed a significant increase in degree of
      medial angulation as the grade increased (p = .000). None of the remaining
      radiographic measurements were significant. A correlation between the hybrid
      radiographic grading system and percentage of actual intraoperative articular
      derangement was shown to exist.

PMID- 11995840
TI  - The effect of first metatarsophalangeal joint arthrodesis on the first ray and
      the medial longitudinal arch: a radiographic study.
AB  - The purpose of this study was to examine the effect of first metatarsophalangeal
      arthrodesis on the sagittal plane orientation of the first ray and the medial
      longitudinal arch. Lateral weightbearing radiographs of 48 patients (54 feet)
      having undergone the procedure were retrospectively reviewed. Patients were
      separated into three groups based on their preoperative diagnosis: hallux
      rigidus, hallux valgus, or rheumatoid forefoot deformity. First metatarsal
      declination, talometatarsal, talar declination, calcaneal inclination, and
      talocalcaneal angles were measured on pre- and postoperative radiographs.
      Multivariate analysis of variance determined that there was a significant
      postoperative change (p < .001) in angular measurements, particularly in the
      first metatarsal declination, talometatarsal, and talocalcaneal angles. There was
      also a significant difference (p < .01) in the angular measurements between the
      hallux rigidus group and the other two groups. However, the amount of change from
      pre- to postoperatively did not vary significantly between the groups. A
      calculation of Pearson correlation coefficients found no significant correlation
      between the hallux dorsiflexion angle and changes in angular measurements. The
      radiographic changes found in this study support Hicks' windlass model: fixed
      dorsiflexion of the hallux causes plantarflexion of the first ray and an increase
      in the medial longitudinal arch.

PMID- 11995841
TI  - To be B or not to be B--is that the question?

PMID- 11995842
TI  - The development of coronary artery surgery: personal recollections.

PMID- 11995843
TI  - Profulla Kumar Sen: his contributions to cardiovascular surgery.
AB  - One of the most eminent cardiothoracic surgeons of India, Profulla Kumar Sen
      (1915-1982) had a keen interest in research and in the subsequent clinical
      application of knowledge gained in the laboratory. His most significant
      contributions are his pioneering work on a transmyocardial acupuncture technique
      for treatment of ischemic myocardium, on heart transplantation in canine models
      and later in human beings, and on a new technique for aortic arch replacement.
      Transmyocardial laser revascularization of the 1990s was but an extension of his
      mechanical myocardial acupuncture for the treatment of ischemic heart disease,
      which he introduced 30 years earlier. On 16 February 1968, after many years of
      preparation through work with animal models, P.K. Sen and his team performed the
      1st cardiac transplantation in India and the 6th in the world.

PMID- 11995844
TI  - Arch-first technique used with commercial T-graft to treat subacute type-A aortic
      dissection in patient with Marfan syndrome.
AB  - Staged repair of extensive thoracic aortic aneurysms puts certain patients at
      risk of rupture. We report the case of a patient with Marfan syndrome who
      presented with subacute type-A aortic dissection and a large descending aortic
      aneurysm. We used the arch-first technique with a commercially available Dacron T
      graft. A clamshell incision was used for exposure. A button of arch vessels was
      anastomosed to the T-graft. Antegrade cerebral perfusion was established through
      the side branch. The distal end of the graft was anastomosed to the descending
      aorta and the proximal end to a composite graft. The duration of cerebral
      ischemia was 30 minutes; antegrade cerebral perfusion lasted 52 minutes. The
      patient experienced no neurologic dysfunction and was discharged with no major
      deficit. This technique shortens brain-ischemia time and is a good option if the
      risk of rupture of the descending component of an extensive thoracic aortic
      aneurysm is high. To the best of our knowledge, this is the 1st reported case in
      which the arch-first technique has been used with a commercially available T
      graft to treat subacute type-A aortic dissection in a patient with Marfan
      syndrome.

PMID- 11995845
TI  - Coronary artery bypass surgery versus coronary stenting: risk-adjusted survival
      rates in 5,619 patients.
AB  - We used the Texas Heart Institute Cardiovascular Research Database to
      retrospectively identify patients who had undergone their 1st revascularization
      procedure with coronary artery bypass surgery (CABG; n=2,826) or coronary
      stenting (n=2,793) between January 1995 and December 1999. Patients were
      classified into 8 anatomic groups according to the number of diseased vessels and
      presence or absence of proximal left anterior descending coronary artery disease.
      Mortality rates were adjusted with proportional hazards methods to correct for
      baseline differences in severity of disease and comorbidity. We found that in
      hospital mortality was significantly greater in patients undergoing CABG than in
      those undergoing stenting (3.6% vs 0.75%; adjusted OR 8.4; P < 0.0001). At a mean
      2.5-year follow-up, risk-adjusted survival was equivalent (CABG 91%, stenting
      95%; adjusted OR 1.26; P = 0.06). When subgroups matched for severity of disease
      were compared, no differences in risk-adjusted survival were seen. A survival
      advantage of stenting was noted in 3 categories of patients: those >65 years of
      age (OR 1.33, P = 0.049), those with non-insulin-requiring diabetes (OR 2.06, P =
      0.002), and those with any noncoronary vascular disease (OR 1.59, P = 0.009). In
      this nonrandomized observational study, CABG had a higher periprocedural
      mortality rate than did percutaneous stenting. At 2.5 years, however, the
      survival advantage of stenting was no longer evident. These data suggest that
      there is no intermediate-term survival advantage of CABG over stenting in
      patients who have multivessel disease with lesions that can be treated
      percutaneously.

PMID- 11995846
TI  - Hypercoagulable state leading to paraplegia in a middle-aged man.
AB  - A 37-year-old man presented with an unusual thrombotic disorder characterized by
      acute paraplegia and the absence of palpable pulses due to extensive arterial
      thrombosis of the aorta and its distal branches. The patient had an extremely
      complicated course that necessitated multiple revascularization procedures over a
      1.5-year period. This case is unusual not only because of its complexity but also
      because of the patient's relatively young age, his lack of risk factors for
      vascular disease, and the presence of a neurologic deficit that improved when
      circulation was restored. More unusual, however, is the fact that all diagnoses
      were excluded except for a high lipoprotein(a) level. To our knowledge, this is
      the 1st reported case in which aortic thrombosis has been related to
      hypercoagulability.

PMID- 11995847
TI  - Ventricular assist device support for management of sustained ventricular
      arrhythmias.
AB  - We describe herein the cases of 2 patients who had ventricular arrhythmias. In
      one, a short-term biventricular assist device, the ABIOMED BVS 5000, was placed
      because the patient had sustained ventricular tachycardia and could not be weaned
      from cardiopulmonary bypass. Excellent hemodynamic support was maintained for
      several days while the antiarrhythmic therapy was maximized. Sinus rhythm was
      restored, and the patient was successfully weaned from the ventricular assist
      device. However, the substrate for the arrhythmia persisted, and a recurrence, 1
      week later, resulted in the patient's death. In the 2nd patient, the use of an
      implantable left ventricular assist device was successful in temporarily
      alleviating the ventricular tachycardia associated with ischemic cardiomyopathy.
      However, after 2 days of device assistance, the patient experienced a recurrence
      of the tachycardia, which degenerated into ventricular fibrillation with a marked
      deterioration in the patient's hemodynamics. The arrhythmia persisted despite
      multiple attempts at external cardioversion, and internal cardioversion and
      placement of an automatic implantable cardioverter-defibrillator were necessary.
      This treatment, along with repeated boluses of amiodarone, led to successful
      suppression of the arrhythmias, and the patient eventually underwent
      transplantation. The mechanical hemodynamic support of the circulation by
      ventricular assist devices was effective in supporting these 2 patients who had
      sustained ventricular arrhythmias.

PMID- 11995848
TI  - Anomalous origin of the right coronary artery from the left coronary sinus: case
      report and literature review.
AB  - A 41-year-old man with no relevant cardiac history presented for evaluation of
      episodic syncope. Electrocardiography showed sinus rhythm with right bundle
      branch block and Q waves in leads II, III, and aVF. Subsequent exercise treadmill
      testing and technetium 99m sestamibi study revealed a reversible posterior
      defect. Coronary angiography later showed a right coronary artery that arose from
      the left coronary sinus--an anomaly that has been associated with angina,
      myocardial infarction, and sudden cardiac death. After being informed of the
      potential risks and options associated with this anomaly, the patient chose long
      term beta-blocker medical therapy. At follow-up, this treatment appeared to have
      resolved his episodic syncope.

PMID- 11995849
TI  - Unruptured aneurysm of the left sinus of valsalva causing coronary insufficiency:
      case report and review of the literature.
AB  - Aneurysm of the left sinus of Valsalva is extremely rare. Compression of the left
      coronary artery by such an aneurysm is an unusual complication of this condition
      and can cause coronary insufficiency. We describe the case of a 75-year-old woman
      who had an isolated unruptured aneurysm of the left coronary sinus with
      intraluminal thrombus, which caused coronary artery compression. We performed
      successful surgical correction by closing the mouth of the aneurysm without
      aortic valve replacement or coronary artery bypass grafting. A review of the
      world medical literature revealed 19 cases of sinus of Valsalva aneurysms that
      hindered the coronary arterial flow. The previously published reports of this
      rare condition and its treatment are discussed herein.

PMID- 11995850
TI  - Stenting for proximal para-anastomotic stenosis of an infrarenal aortic bypass
      graft.
AB  - We present a case in which endovascular stenting was used for recurrent proximal
      para-anastomotic stenosis 11 years after aorto-bi-iliac bypass grafting for
      severe aorto-iliac occlusive disease. A 55-year-old woman presented with
      worsening bilateral hip and buttock claudication. At presentation, her resting
      ankle-brachial indices were 0.87 bilaterally and decreased to 0.39 on the right
      and 0.40 on the left with exercise. Aortography demonstrated a proximal para
      anastomotic aortic graft stenosis without distal outflow obstruction, patent
      superficial femoral arteries, and good triple-vessel runoff bilaterally The
      stenosis was dilated with a 9- x 4-cm OPTA balloon angioplasty catheter. A Palmaz
      stent (P424, Cordis) was mounted on a 10- x 4-cm OPTA balloon catheter and
      deployed across the proximal stenosis. Completion arteriography confirmed
      adequate placement and reduction in the degree of stenosis. There was no pressure
      gradient across the proximal anastomosis. At our patient's 1-week follow-up
      visit, her resting ankle-brachial indices were both greater than 1.0 and her
      exercise ankle-brachial indices were 1.0 bilaterally She remained asymptomatic at
      13 months. Most late sequelae of aortic graft surgery involve the distal
      anastomosis and are resolved surgically without complicated techniques. However,
      revision at the proximal anastomosis involves the aorta directly and therefore
      requires open abdominal dissection and aortic cross-clamping. Percutaneous aortic
      stenting for primary aortoiliac disease has been shown to reduce operative time,
      cost, and hospital stays, to improve patency and to be durable. Our clinical
      experience with aortic stenting for primary disease led us to consider this
      procedure for recurrent proximal stenosis.

PMID- 11995851
TI  - Exercise testing induces fatal thromboembolism from mechanical mitral valve.
AB  - Thromboembolism is still one of the most important complications of prosthetic
      heart valves. Embolism to a major coronary branch is rare, but acute proximal
      occlusions can be fatal, even when the coronary arteries are otherwise normal and
      intervention is rapid. We report a fatal complication of an exercise test in a
      patient who had a St. Jude bileaflet mitral valve. After an exercise test, a 42
      year-old woman with a mechanical prosthetic valve had a severe hemodynamic
      collapse with acute ST segment changes. Coronary angiography showed a totally
      occluded left main coronary artery with TIMI grade 0 to 1 flow. Rapid injection
      of contrast material and the passage of a floppy guidewire through the thrombus
      restored a TIMI grade 3 flow. Angiography showed no coronary atherosclerostic
      involvement. Despite successful coronary reperfusion, intra-aortic balloon
      counterpulsation, and intensive medication, the patient died. This case
      demonstrates that exercise testing should be applied with great caution in
      patients with prosthetic valves, and only after a careful evaluation of valve
      function. We recommend transesophageal echocardiography prior to exercise testing
      in these patients.

PMID- 11995852
TI  - Pneumopericardium in a patient with AIDS.
AB  - In 1997, a 53-year-old male smoker was admitted for progressive shortness of
      breath associated with a productive cough and yellowish sputum, pleuritic chest
      pain, and low-grade fever. There was no history of trauma. A posterior-anterior
      chest radiograph showed a diffuse infiltrate through the right lung field and an
      air space parallel to the lateral border of the heart. A computed tomographic
      scan of the chest confirmed pneumopericardium, with no associated pericardial
      effusion. It also showed a cavitary infiltrate in the anterior basal segment of
      the right lower lobe, but no definite neoplasm. Cultures of the sputum grew
      Staphylococcus aureus. The patient had positive antibodies to human
      immunodeficiency virus (HIV), hepatitis A, and hepatitis B. A bronchial biopsy
      from the right lower lobe showed well differentiated infiltrating squamous cell
      carcinoma with an acute inflammatory exudate. No bronchopericardial fistula was
      noted. After antibiotic treatment, a repeat chest radiograph showed resolution of
      pneumopericardium and improvement of the chest infiltrate. Repeat computed
      tomography of the chest showed that the pneumopericardium had resolved, but now
      revealed a large pericardial effusion. No bronchopericardial fistula could be
      demonstrated. Unfortunately, our patient refused further investigation.
      Pneumopericardium is a rare disorder. In adults, pneumopericardium most commonly
      results from trauma. Although many other reports link pneumopericardium to an
      underlying disease process, our patient with HIV antibodies developed
      pneumopericardium despite having no history of trauma and no documentation of a
      communicating fistula. To our knowledge, there has been no previous report of
      pneumopericardium in association with acquired immunodeficiency syndrome.

PMID- 11995853
TI  - Coronary-coronary bypass using vein graft on a beating heart in a patient with
      porcelain aorta.
AB  - There is increased risk of systemic embolism during cardiopulmonary bypass in
      patients with a severely atherosclerotic ascending aorta. We report a coronary
      coronary bypass in a 74-year-old man with a porcelain aorta. He underwent a
      proximal right coronary-distal right coronary artery bypass with a saphenous vein
      graft, combined with a pedicled arterial graft (left internal mammary artery) to
      the left anterior descending artery, in the presence of a beating heart without
      cardiopulmonary bypass. The patient survived without evidence of perioperative
      myocardial infarction or cerebrovascular accident. One year later, follow-up
      angiography showed graft patency with good distal run-off. Coronary-coronary
      bypass on a beating heart without cardiopulmonary bypass can be performed safely
      in a patient with porcelain aorta.

PMID- 11995854
TI  - Improved device for sutureless aortic anastomosis applied in a case of cancer.
AB  - To reduce the time needed for clamping or circulatory arrest (or both) during
      substitution of a prosthesis for the thoracic aorta, we developed an expandable
      device that can be used with any commercially available prosthetic graft to
      enable sutureless aortic anastomosis. Improvements upon a previous version of the
      device include the use of nickel-titanium alloy (Nitinol) instead of stainless
      steel. This, together with an improved wire-looping design, now enables
      continuous control of diameter, even when the device is in contact with blood. A
      further improvement consists of 4 metallic hooks on the outer surface, which
      enable firm fixation to the aortic stump. In March 2001, a 47-year-old man was
      admitted to our institution for evaluation of left upper-lobe bronchogenic
      adenocarcinoma that had infiltrated the distal aortic arch and upper descending
      aorta. Re-staging of the neoplasm ruled out distant metastasis. We resected the
      infiltrated aortic wall en bloc with the upper lobe. The expandable device
      enabled the distal anastomosis of the aortic prosthesis to be performed easily,
      in less than 3 minutes. The main advantages of this device are an easier, quicker
      anastomosis and the absolute prevention of suture-line hemorrhage (no suture
      line). The expandable device overcomes the drawbacks of the intraluminal ringed
      prosthesis used in the past.

PMID- 11995855
TI  - High-grade atherosclerosis of the aorta.

PMID- 11995856
TI  - A ring in the right atrium.

PMID- 11995857
TI  - Giant left atrial myxoma presenting with mitral valve obstruction.

PMID- 11995858
TI  - Cardiac tamponade and electrical alternans.

PMID- 11995859
TI  - Pulmonary artery-to-left atrium communication.

PMID- 11995860
TI  - Hazards of chest tubes after pneumonectomy.

PMID- 11995861
TI  - Saddle embolus in Ethiopia.

PMID- 11995862
TI  - Balloon sizing of atrial septal defects.

PMID- 11995863
TI  - Pollutant export from various land uses in the upper Neuse River Basin.
AB  - Because of the relatively high variability of pollutant export from urban land
      uses, a significant number of monitoring studies, including data from many
      storms, are needed to adequately characterize export from urban land uses.
      Pollutant runoff from six small drainage areas with different land uses was
      monitored for at least 20 storm events over the course of more than 1 year. The
      land uses included single-family residential, golf course, industrial, dairy cow
      pasture, construction site, and wooded site. Average event mean concentrations
      and total annual load were computed for nitrogen forms, total phosphorus, and
      sediment from the land uses. Annual total nitrogen export was greatest for the
      construction land use during the house-building phase, followed closely by the
      residential and golf course land uses. Total phosphorus export was greatest for
      the golf course site followed by the pasture and residential land uses. Sediment
      export was greatest for the construction site during the rough grading phase,
      which averaged more than 10 times more sediment export than any of the other
      sites. To estimate export from a multiuse urban watershed, total nitrogen,
      phosphorus, and sediment export from the residential, golf course, and
      construction sites were averaged. The average total nitrogen, phosphorus, and
      sediment export from the three land uses was, respectively, 269, 302, and 256%
      greater than the corresponding exports from the wooded site, which was considered
      similar to the predevelopment land use. Additionally, analyses of rainfall
      samples indicated that a considerable portion of the nitrogen export from these
      sites likely comes from nitrogen in rainfall.

PMID- 11995864
TI  - Catalytic wet oxidation of 2,4-dichlorophenol solutions: activity of the
      manganese-cerium composite catalyst and biodegradability of the effluent stream.
AB  - Aqueous solutions containing 100 to 1000 mg/L of 2,4-dichlorophenol (2,4-DCP)
      were oxidized in an upflowing fixed-bed reactor in this study of manganese-cerium
      composite catalysts, which were prepared by the coprecipitation of both manganese
      nitrate and ceric nitrate at various molar concentrations. Results showed that
      2,4-DCP conversion by wet oxidation in the presence of the manganese-cerium
      composite catalysts was a function of the molar ratio of the manganese-cerium
      catalyst. The kinetic behavior of 2,4-DCP oxidation with catalysis could be
      explained by using a zero-order rate expression. Total organic carbon (TOC)
      removal by wet oxidation in the absence of any catalyst was nil, while
      approximately 68% TOC reduction was achieved during wet oxidation over a
      manganese-cerium (7:3 mol/mol) catalyst at 160 degrees C and an oxygen partial
      pressure of 1.0 MPa. Moreover, the 5-day biochemical oxygen demand/chemical
      oxygen demand ratios of all the effluent streams were determined to be greater
      than 0.45 as the wet catalytic processes were carried out at a liquid hourly
      space velocity less than 24 h (-1), indicating that they could be made more
      amenable to further biological treatment.

PMID- 11995865
TI  - Disinfection of wastewater by hydrogen peroxide or peracetic acid: development of
      procedures for measurement of residual disinfectant and application to a
      physicochemically treated municipal effluent.
AB  - The Montreal Urban Community Wastewater Treatment Plant (MUCWTP) located in
      Montreal. Quebec, Canada, uses physicochemical treatment processes prior to
      discharging wastewater into the St. Lawrence River via an outfall tunnel of 2
      hours retention time. Although chlorination facilities exist, they are not being
      used, and the MUCWTP is seeking alternative methods for disinfection to achieve a
      2- to 3-log fecal coliform reduction. Liquid chemical disinfectants were
      attractive options because of their low capital costs. This led to an
      investigation of the feasibility of using hydrogen peroxide or peracetic acid. A
      method for measuring peroxycompounds (hydrogen peroxide or peracetic acid plus
      hydrogen peroxide) was developed using the peroxidase-based oxidation of 2,2'
      azino-bis(3-ethylbenz-thiazoline-6-sulfuric acid) diammonium salt (ABTS) with
      hydrogen peroxide. The validity of the method was confirmed using effluent from
      the MUCWTP. Recovery was higher than 90% for peracetic acid levels as low as 1.0
      mg/L. Quenching of hydrogen peroxide was achieved with 50-mg/L catalase;
      quenching of peracetic acid was achieved with 100 mg/L of sodium thiosulfate,
      followed by 50 mg/L of catalase. Batch disinfection tests were conducted on
      MUCWTP effluent. Hydrogen peroxide and peracetic acid in wastewater over time
      could be modeled as a second-order decay, with the decay "constant" being a
      function of the initial concentration of peroxycompounds. This function was the
      same for both hydrogen peroxide and peracetic acid, possibly indicating similar
      decomposition pathways in wastewater matrices. Disinfection was modeled using a
      modified Hom equation. Required doses of hydrogen peroxide to reach the target
      fecal coliform levels ranged from 106 to 285 mg/L, with the higher doses
      occurring when ferric chloride instead of alum was used as the coagulant. Hence,
      hydrogen peroxide was infeasible as a disinfectant for this application. On the
      other hand, the peracetic acid dose needed to achieve the target fecal coliform
      level was only 0.6 to 1.6 mg/L. Therefore, peracetic acid seems to be a promising
      disinfectant for physicochemical or primary effluent, or combined sewer
      overflows.

PMID- 11995866
TI  - Optimization of biofiltration for odor control: model development and parameter
      sensitivity.
AB  - A dynamic model that describes the mass transport and attenuation of odor-causing
      air emissions (i.e., hydrogen sulfide and other reduced sulfur compounds) in a
      biofiltration unit was developed and incorporated into a software package called
      Biofilter. Mechanisms included advective flow, mass transfer from the bulk phase
      to the biofilm, biofilm internal diffusion, and biological reaction in the
      biofilm. A dimensionless analysis revealed that the mass transport and
      attenuation of target compounds can be characterized by several dimensionless
      groups. Model equations were converted to ordinary differential equations using
      orthogonal collocation and the resulting ordinary differential equations were
      solved using the DGEAR algorithm. Numerical solutions were verified by comparing
      model simulations to analytical solutions. The model simulations showed that the
      existence of a water layer surrounding the biofilm in a biofiltration unit lowers
      the removal efficiency of hydrogen sulfide. A sensitivity analysis of model
      parameters (including the film transfer coefficient, biofilm diffusivity, biofilm
      thickness, maximum specific biomass growth rate, yield coefficient, half
      saturation coefficient, and initial active biomass concentration) using data from
      two biofilters located at the Cedar Rapids (Iowa) Water Pollution Control
      Facilities, showed that biofilm internal diffusion and biofilm kinetics have a
      significant effect on hydrogen sulfide removal, while external mass transfer has
      little effect.

PMID- 11995867
TI  - The effect of chlorination on organocyanide compounds.
AB  - Results are presented that explore the possibility of organocyanide compounds in
      wastewater contributing to elevated cyanide levels in the chlorinated effluents
      of publicly owned treatment works. Four model compounds, acetonitrile, amygdalin,
      cyanocobalamin, and 2-acetoxy-3-butenenitrile, were selected and tested with
      varying chlorine dosages for release of cyanide by total and diffusible cyanide
      procedures. The coenzyme form of vitamin B12, which does not contain cyanide, was
      also tested. It was found that acetonitrile and amygdalin do not yield cyanide
      with or without chlorination, cyanocobalamin had increased release with increased
      chlorine dosages, and 2-acetoxy-3-butenenitrile had generally decreased release
      of cyanide with increased chlorine dosages. Both cyanocobalamin and coenzyme
      vitamin B12 gave evidence of the formation of the cobalt-cyanide complex after
      chlorination, even though the molecular structure of the coenzyme vitamin B12
      contains no cyanide.

PMID- 11995868
TI  - The role of poly-hydroxy-alkanoate form in determining the response of enhanced
      biological phosphorus removal biomass to volatile fatty acids.
AB  - Anaerobic-aerobic batch experiments indicated that poly-hydroxy-alkanoate (PHA)
      form was important in determining the net phosphorus removal resulting from
      different volatile fatty acids (VFAs). Poly-3-hydroxy-butyrate (3HB) content was
      found to correlate fairly well with higher observed aerobic phosphorus uptake per
      unit PHA carbon degraded. Poly-3-hydroxy-valerate (3HV) correlated with lower
      aerobic phosphorus uptakes per unit PHA carbon degraded. These experiments,
      conducted with synthetic wastewater, imply that VFA speciation might have a
      significant effect on aerobic phosphorus uptakes and net phosphorus removal. In
      addition, the model parameter fP.UPT (Barker and Dold, 1997) could vary with the
      proportion of acetic to propionic acid received (i.e., the acetic/propionic acid
      ratio may be an important parameter for these systems). Carbohydrate data implied
      that the lower aerobic phosphorus uptake resulting from 3HV might have been
      caused by a greater fraction of PHA carbon shunting to carbohydrate biosynthesis
      during aerobiosis.

PMID- 11995869
TI  - A new process for enriching nitrifiers in activated sludge through separate
      heterotrophic wasting from biofilm carriers.
AB  - A new process, the biofilm-activated sludge innovative nitrification (BASIN)
      process, consisting of a moving-bed biofilm reactor (MBBR) with separate
      heterotrophic wasting, followed by an activated-sludge process, has been proposed
      to reduce the volumetric requirements of the activated-sludge process for
      nitrification. The basic principle is to remove chemical oxygen demand on the
      biofilm carriers by heterotrophic organisms and then to waste a portion of the
      heterotrophic biomass before it can be released into the activated-sludge
      reactor. By this means, the amount of heterotrophic organisms grown in the
      activated-sludge reactor is reduced, thereby reducing the volume of that tank
      needed for nitrification. For nitrification applications, the simplest method for
      stripping biomass was to use an in-tank technique using high shearing rates with
      aeration. Bench-scale testing showed sludge yields in the BASIN process were one
      half of that in a control activated-sludge process and twice that of a process
      line with intermediate settling between the MBBR and activated-sludge stage.
      Critical washout solids retention times for nitrifiers were the same for all
      three lines, so activated-sludge volumes for the BASIN process could be reduced
      by 50% compared with the control. Originally conceived process concepts for the
      BASIN process were confirmed by the experimental work.

PMID- 11995870
TI  - Effect of some environmental factors on mercury(II) reduction by suspended
      particulate matter-associated Kluvera cryocrescens biofilms in waterbodies.
AB  - To resist the invasion of harmful external substances, microorganisms tend to
      attach to submerged surfaces in aquatic systems. The current study focused on the
      influence of environmental factors (e.g., pH value of the culture, oxidation
      reduction condition, light, and cultured age of bacteria on the reduction of
      mercury(II) to elemental mercury (Hg0) that occurred on the surfaces of suspended
      particulate matter. A simulated biofilm system consisting of bacterium Kluvera
      cryocrescens separated from suspended particulate matter in the Yangtze River
      (China), its exopolysaccharide, and kaolinite (BEK) was used to study the
      transformation of mercury(II) in an aquatic system. The results showed that the
      reduction of mercury from mercury(II) to elemental mercury was favored in a
      neutral pH, light, and aerobic surrounding while a low pH, dark, and anaerobic
      condition inhibited the reaction. Moreover, the reduction capacity of both
      biofilms and free bacteria decreased with the increase of cultured age. Under all
      experimental conditions, the reduction capacity of biofilms was lower than that
      of the free bacteria, suggesting that biofilm, as a microecosystem, might
      function as a buffer to protect the effect of mercury(II) and the surrounding
      change on microorganisms.

PMID- 11995871
TI  - Association of urban runoff with coastal water quality in Orange County,
      California.
AB  - The associations between storm events, urban runoff, and coastal water quality
      have not been well investigated. A temporal and spatial analysis of 2 years of
      data was conducted to determine associations between urban river discharge and
      indicator bacteria levels for Southern California beaches and evaluate the
      contribution of anomalous precipitation to the association. Data show beaches
      next to rivers had the highest bacterial levels in both wet and dry seasons.
      Bacterial levels rose substantially across all sites during wet months, and river
      discharge and bacterial levels were all highest during the winter with the most
      rainfall. Precipitation was significantly associated (Spearman rank bivariate
      correlation, P < 0.01) with water discharged from the rivers. River discharge was
      significantly associated with bacterial levels at 20 out of 22 beaches, with the
      strongest associations at sites next to rivers. The results indicate that urban
      river discharge is a primary source of Southern California's coastal water
      pollution and, as a result, swimming at beaches near rivers may pose a
      significant public health risk. The strong association found between
      precipitation and water pollution may be relevant to studies of potential health
      effects associated with climate change.

PMID- 11995872
TI  - Reduction of enteric microbes in flushed swine wastewater treated by a biological
      aerated filter and UV irradiation.
AB  - An aerobic biofilter system was studied to assess its effectiveness for reducing
      enteric microbial indicators in flushed swine wastewater under different seasonal
      conditions. A laboratory-scale, low-pressure UV collimated beam apparatus was
      used to investigate the effectiveness of UV irradiation for inactivating enteric
      bacteria, coliphages, and bacterial spores in treated and untreated swine
      wastewater having unfiltered absorbances of 5 to 11 cm(-1) and total suspended
      solids concentrations of 500 to 1200 mg/L. Fecal coliforms, Escherichia coli,
      enterococci, somatic coliphages, and male-specific coliphages were reduced by 97
      to 99% in the biofilter system when reactor water temperatures were between 23
      and 32 degrees C. Salmonella were reduced by 95 to 97% when water temperatures
      were 17 to 32 degrees C. Of the six microbial indicators studied. Clostridium
      perfringens spores were typically reduced the least by the biofilter system. At
      an average absorbed UV irradiation dose of 13 mJ/cm2, maximum reductions of fecal
      coliforms, E. coli, enterococci, C. perfringens spores, and somatic coliphages in
      biofilter system effluent were 2.2, 2.1, 1.3, 0.2, and 2.3 log10, respectively.
      The results of this study show that the aerobic biofilter system can be an
      effective alternative for treatment of flushed swine waste. Ultraviolet
      irradiation can be effective for further reducing enteric microbe concentrations
      in biologically-treated swine waste, as well as in lower quality wastewaters,
      indicating its general potential for pathogen reductions in low-quality
      wastewaters intended for beneficial reuse.

PMID- 11995873
TI  - Malignant lymphoma of bone.
AB  - Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed
      because of unspecific clinical signs and equivocal radiographs. Therapy in
      general is multimodal, including surgery and radio- and chemotherapy. Our
      objective was to demonstrate the clinical and radiological aspects of the lesion
      to optimize diagnostic approaches and to evaluate treatment and prognostic
      factors. Thirty-six patients with malignant lymphoma of bone who were surgically
      treated over a 15-year-period were retrospectively reviewed. Seventeen of them
      showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as
      primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease
      with multiple bone or visceral involvement was apparent (dNHL). Six patients
      suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment
      was indicated for diagnostic reasons or complications due to the disease.
      Radiation and chemotherapy were part of the oncological treatment. The patients'
      mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients
      was pain, with an average duration of 8 months. In the secondary cases, bone
      involvement appeared on average 57 months after the initial diagnosis. An
      osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was
      seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic
      sign associated with this disease. The 5-year survival rate was 61% (PLB 88%,
      dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant
      factor in the prognosis. Extraskeletal involvement significantly decreased
      survival. No correlation was found between gender, age, location, or histological
      subtypes and survival. Bone involvement in NHL appears late in the extraskeletal
      disease. The clinical appearance is nonspecific, and the delay between the onset
      of symptoms and diagnosis is often long. One of the major radiologic signs is the
      existence of a soft-tissue tumor surrounding the bone with little or no bone
      involvement on plain films. Treatment generally is conservative, based on the
      stage of the disease. Local radiation with or without systemic chemotherapy
      should be used. The long-term survival is favorable, but dependent on the stage
      of the disease and the amount of bone involvement.

PMID- 11995874
TI  - Oncologic and functional results after treatment of giant cell tumors of bone.
AB  - Surgical treatment of giant cell tumor of bone has always been a difficult
      problem because of its local aggressive behavior. Oncologic results and
      functional outcome are reported here in a retrospective study of 36 patients,
      treated by various surgical procedures. The average age at the time of diagnosis
      was 34 years, and the median follow-up period was 7 years. Twenty-three patients
      were treated by intralesional excision with local adjuvant therapy, and 11
      patients by extralesional excision. Two patients received radiotherapy only.
      Seven local tumor recurrences (30%) were encountered after intralesional
      procedures, while local tumor control was the rule after extralesional excision.
      Intralesional excision with local adjuvant therapy resulted in significantly
      better functional results compared with extralesional excision. Wide excision was
      associated with a poor functional outcome and marginal excision with a good
      functional outcome. For the treatment of giant cell tumor of bone, intralesional
      excision with local adjuvant therapy is recommended because of a good functional
      outcome. When applying cryosurgery as the local adjuvant, more vigorous freezing
      may be necessary to improve local tumor control.

PMID- 11995875
TI  - Results of a prospective randomised study comparing a non-invasive surgical
      zipper versus intracutaneous sutures for wound closure.
AB  - A prospective randomised study was undertaken to investigate the advantages and
      disadvantages of a non-invasive surgical zipper (Medizip) vs intracutaneous
      sutures skin closure in orthopaedic surgery. The study group consisted of 120
      consecutive patients, 45 men and 75 women with a mean age of 47 years. The
      Medizip was used in 20 surgical knee wounds, 20 hip wounds and 20 orthopaedic
      spine wounds. The same number of patients received intracutaneous sutures.
      Handling, wound healing and scar formation on day 1, at 2 weeks and 6 weeks were
      evaluated. The average time for wound closure with the zipper was 2 min and 9.4
      min when the wound was closed with intracutaneous sutures (p = 0 .01). Patients
      were positive in their assessment of the wound healing progress and results; they
      found the skin closure device agreeable to wear. The scar result was rated very
      good in 82% (n = 4 9) of the zipper group, and 85% (n = 5 1) in the
      intracutaneous group (p = 0 .67). Based on the results obtained, the non-invasive
      skin closure system Medizip represents a safe option in the spectrum of surgical
      wound treatment.

PMID- 11995876
TI  - Conservative treatment of Garden stage I femoral neck fracture in elderly
      patients.
AB  - We reviewed 38 patients aged 65 years and older with fresh Garden stage I femoral
      neck fractures treated nonsurgically to determine factors that influence fracture
      union. The mean follow-up period was 20 (range 6-86) months. Twenty-three (61%)
      fractures united within 6 months after injury, while 15 (39%) failed to unite.
      The percentage of united fractures was considerably higher (p < 0.01) in patients
      who began bed-to-wheelchair transfer training 14 days or later after injury than
      in those who began training within 13 days. The incidence of union was
      considerably higher (p < 0.05) in patients who began ambulation 20 days or later
      after injury than in those who began within 19 days. There was no statistical
      difference in the amount of valgus or retroversion of the femoral head between
      patients whose fractures united and those whose fractures did not. Patients
      without severe dementia regained the ability to walk significantly more
      frequently than did patients with severe dementia (p < 0.05).

PMID- 11995877
TI  - The long-term effect of pelvic osteotomy on birth canal size.
AB  - The effect of pelvic osteotomy on birth canal size at skeletal maturity is
      unknown. This information would be useful to counsel women of reproductive age
      who have undergone pelvic osteotomy. It was the purpose of this study to answer
      that question. A retrospective review of girls who had undergone pelvic osteotomy
      in the period 1980-1999 was performed. Transverse plane birth canal dimensions
      (inlet, mid-pelvis, and outlet) were measured from radiographs before and after
      osteotomy and at final follow-up. Final follow-up diameters were compared to
      threshold values (obstetric pelvimetry and clinical guidelines). There were 37
      patients (40 osteotomies: 31 Salter, 5 Steel, 2 Chiari, and 2 Ganz). The average
      age at osteotomy was 7.5 +/- 5.3 years (range 2.0-21.3 years), and at final
      follow-up was 16.0 +/- 4.7 years (range 2.9-25.7 years); the average follow-up
      was 8.5 +/- 5.2 years (range 0.5-17.6 years). The effect of osteotomy at skeletal
      maturity was investigated by analyzing the 30 children > or = 14 years of age at
      the final follow-up. The pelvic inlet was above the threshold for all 30
      children. The mid-pelvis was below the low normal threshold (9.5 cm) in 3 of 21
      Salter, 2 of 5 Steel, and 1 of 2 Chiari osteotomies. The pelvic outlet was below
      the threshold in 2 of 21 Salter and 2 of 5 Steel osteotomies. The mid-pelvis
      dimensions were narrower in those who underwent osteotomy when older: 7.1 +/- 4.9
      years (n = 24) and 11.9 +/- 7.9 years (n = 6) (p = 0.06) for those above and
      below the 9.5 cm mid-pelvis threshold, respectively. In conclusion, 6 of the 30
      cases had a mid-pelvis which was below threshold at skeletal maturity. If the
      transverse mid-pelvis diameter at skeletal maturity is < 9.5 cm, then the
      likelihood of Cesarean section is increased, and this information should be given
      to the patient.

PMID- 11995878
TI  - Surgical treatment of basal joint disease of the thumb: comparison between
      resection-interposition arthroplasty and trapezio-metacarpal arthrodesis.
AB  - Thirty-six thumbs with symptomatic osteoarthritis of the first carpometacarpal
      joint were treated either by trapezio-metacarpal arthrodesis (n = 18) or
      resection-tendon-interposition arthroplasty (n = 18). The mean follow-up of the
      29 patients was 42 months. With the data available, we could not find any
      difference in the outcome of either procedure. In the majority of cases, the main
      aim of the operation, relief of pain, was achieved, the patients were satisfied
      and pleased with the functional result of the operation. No difference in grip
      strength between the operated and the normal contralateral hand could be
      established. Nevertheless, the arthrodesis seems to be the procedure causing
      fewer problems (only one patient not completely satisfied) and is therefore
      preferred over the resection-tendon-interposition arthroplasty.

PMID- 11995879
TI  - Adjacent segment degeneration after lumbar spinal posterolateral fusion with
      instrumentation in elderly patients.
AB  - This retrospective study investigated adjacent segments radiologically and
      clinically after posterolateral fusion of the lumbar spine with instrumentation.
      Thirty-two patients over 60 years old with a postoperative follow-up of at least
      4 years were included. These patients all met the criteria of a postoperative
      symptom-free period of over 2 years, evident fusion mass seen on plain
      radiographs, and no implant breakage or loosening. There was 81.3% excellent and
      good clinical results (26/32). For all patients, flexion and extension views of
      the lumbar spine were done preoperatively and postoperatively. Adjacent segments
      below the fusion, above the fusion, and cranial to the above adjacent segment
      were examined. Three patients each with translation > 4 mm in adjacent segments
      were found in both the short and long (> or = 3 segments) fusion groups. The
      incidence was 16.7% (3/18) in the short fusion group and 21.4% (3/14) in the long
      fusion group. However, no statistically significant difference (p = 0.7878) was
      found according to the Fisher exact test. Comparing the effect of different types
      of instruments, there still was no statistically significant difference (p =
      0.1161) between the VSP plate and Isola rod groups in inducing degeneration of
      adjacent segments after posterolateral fusion of the lumbar spine. After
      measuring the mobility of degenerated adjacent segments, relative hypermobility
      was more likely responsible for the accelerated degeneration rather than the
      absolute increase of mobility.

PMID- 11995880
TI  - Requirements for NF-kappaB activation in hemorrhagic shock.
AB  - The activation of nuclear factor (NF)-kappaB contributes to the dysfunctional
      inflammatory response accompanying resuscitation from hemorrhagic shock (HS), in
      part through induction of pro-inflammatory cytokines including granulocyte colony
      stimulating factor (G-CSF) and interleukin (IL)-6. In previous studies, we
      demonstrated that G-CSF and IL-6 up-regulation required both the ischemic and
      resuscitation phases of HS. In this study, we examined whether or not both phases
      of HS were required for NF-kappaB activation and the kinetics of its activation.
      Sprague-Dawley rats were subjected to unresuscitated HS with increasing duration
      of the ischemic phase [compensated HS, 0% shed blood return (SBR); decompensated
      HS, 35% SBR; and irreversible HS, 70% SBR) or HS (compensated or decompensated)]
      followed by resuscitation. NF-kappaB activity did not increase in any of the
      unresuscitated groups compared with sham controls. In contrast, resuscitation as
      early as 1 h following HS resulted in increased NF-kappaB activity compared with
      both the unresuscitated shock group and sham controls; NF-kappaB activation
      persisted for 8 h. Thus, NF-kappaB activation requires both phases of HS, occurs
      rapidly following resuscitation, and persists throughout the early stages of
      dysfunctional inflammation following resuscitation.

PMID- 11995881
TI  - Removal of well-fixed or porous-coated cementless stems in total hip revision
      arthroplasty.
AB  - The removal of well-fixed or porous-coated cementless stems is demanding and
      associated with a hig perioperative risk to the patient. Only a few surgical
      techniques have been published about this procedure. We introduce a special,
      ballistically driven, flexible chisel for the disruption of bone ingrowth or
      fibrous encapsulation. In six cases the stem removal was successful after 8-15
      min (average 12,2 min) without damage to the bone. Reimplantation is possible
      with standard stems for primary surgery. This surgical technique leads to a
      predictable procedure, reduces the risk for the patient, the operation time and
      costs. We are continuing with this technique under supervision by the local
      Ethics Commission.

PMID- 11995882
TI  - Humeral shaft fractures as predictors of intra-abdominal injury in motor vehicle
      collision victims.
AB  - To assess the utility of humeral shaft fractures as predictors of organ injuries
      and skeletal injuries in multiply injured patients involved in motor vehicle
      collisions (MVCs). A prospectively collected database of multiply injured motor
      vehicle occupants with an Injury Severity Score (ISS) greater than 12 admitted to
      a level I regional trauma centre during a 102-month period (January 1992 to June
      2000) was reviewed to assess skeletal and organ injuries associated with a
      humeral shaft fracture. The effect of occupant location within the vehicle, the
      point of collision, and the use of a seat belt restraint was also examined to
      identify trends in injury patterns. Data from 1070 motor vehicle occupants - 65
      with concomitant humeral shaft fractures and 1005 without humeral shaft fractures
      - revealed that 63% of motor vehicle occupants who sustained humeral fractures
      were drivers, compared with 77% in the non-humeral fracture group. Those patients
      who sustained a humeral shaft fracture had a significantly greater number of
      liver injuries (p = 0.022), forearm/hand fractures (p < 0.001), tibial fractures
      (p < 0.01) and femoral fractures (p < 0.01) compared with controls. A lateral
      collision impact showed a trend towards increased splenic and hepatic injuries
      within the humeral shaft fracture group. The presence of a humeral shaft fracture
      in a multiply injured patient involved in a MVC is significantly associated with
      an increased incidence of both upper and lower extremity fractures and liver
      injury. Moreover, humeral shaft fractures may serve as a predictor of potential
      intra-abdominal pathology in multiply injured trauma patients involved in MVCs.

PMID- 11995883
TI  - Comparison of two different posterior approachs for hemiarthroplasty of the hip.
AB  - A prospective study was undertaken on 183 patients who had suffered a femoral
      neck fracture between 1998 and 1999. The aim was to compare the complication
      rates for the classical posterior approach and the modified posterior approach.
      The modified posterior approach used was the one described by Williams et al.,
      which preserved the pyriformis, the labrum and the capsule. Group 1 included 95
      patients, who were operated on by the posterior approach. Group 2 included 88
      patients, who were operated on by the modified posterior approach. The
      dislocation rate for the posterior approach was 7.4% (7 cases), and 1.1% (1 case)
      for the modified posterior approach. This difference was statistically
      significant (p < 0.05). There were no significant differences in the incidences
      of other intraoperative and postoperative complications. We concluded that the
      modified posterior approach significantly increases the stability of a
      hemiarthroplasty in relation to the classical posterior approach.

PMID- 11995884
TI  - Osteolytic lesion in the greater trochanter mimicking tumor.
AB  - Two patients with an osteolytic lesion of the greater trochanter suggesting a
      malignant bone tumor are presented. Biopsy, microbiological and histological
      examination suggested a diagnosis of trochanteric tuberculosis. Treatment
      consisted of multiple surgical debridements and antituberculous chemotherapy. The
      incidence of similar cases is expected to increase with the rising incidence of
      tuberculosis.

PMID- 11995885
TI  - Melorheostosis with occlusion of dorsalis pedis artery.
AB  - Melorheostosis is an unusual sclerotic dysplasia of bone. The case of a 51-year
      old female patient with melorheostosis and occlusion of the dorsalis pedis artery
      is described. Although numerous vascular anomalies have been noted in patients
      with melorheostosis, occlusion of the dorsalis pedis artery has not been reported
      previously.

PMID- 11995886
TI  - Sacral insufficiency fracture, an unsuspected cause of low-back pain in elderly
      women.
AB  - Sacral insufficiency fractures (SIF) usually occur in elderly women and are
      secondary to various conditions, mainly postmenopausal or steroid-induced
      osteoporosis and radiation therapy. They are often overlooked or confused
      clinically and radiographically with metastatic disease. We report a case of a 72
      year-old woman who presented to our department with severe low-back pain. She was
      thoroughly investigated for the cause of her back pain. Plain X-rays did not
      reveal any abnormality, but magnetic resonance (MR) scan revealed marked oedema
      within both sides of the sacrum, suggesting a neoplastic lesion. Bone
      scintigraphy did show a hyperfixation pattern forming an 'H' in the sacrum which
      is a characteristic sign of SIF. Computed tomography (CT) confirmed sclerotic
      changes interpreted as insufficiency fractures through both sacral alae.
      Increased awareness of these fractures may help to avoid unnecessary
      investigations and treatment. Bed rest and analgesia followed by rehabilitation
      provide good relief of symptoms.

PMID- 11995887
TI  - Fatal retroperitoneal hemorrhage caused by perforation of a guidewire pin for
      proximal femur fixation.
AB  - A 77-year-old woman with a slightly displaced intertrochanteric two-fragment
      fracture of the left hip was treated by internal fixation using a screw-nail
      device (gamma nail). After the operation she became hemodynamically unstable, and
      ultrasound revealed a large retroperitoneal fluid accumulation in the left lower
      abdomen. A contrast computed tomogram revealed active hemorrhage next to the
      quadrilateral surface of the left acetabulum. Selective angiography and
      embolization were immediately initiated and stopped the bleeding. However,
      despite the successful treatment of the retroperitoneal hemorrhage, the patient
      developed an oligosymptomatic myocardial infarction associated with clinical
      evidence of a cerebrovascular insult and pulmonary decompensation and died 2
      weeks after her accident. The hemorrhage in this patient was most likely caused
      by surgical damage to the obturator artery during placement of the guidewire pin
      (with threaded tip) to position the screw of the implant.

PMID- 11995888
TI  - International scope of medical care.

PMID- 11995889
TI  - Changes in hip spasticity and strength following selective dorsal rhizotomy and
      physical therapy for spastic cerebral palsy.
AB  - Hip adductor spasticity and strength in participants with cerebral palsy (CP)
      were quantified before and after selective dorsal rhizotomy (SDR) and intensive
      physical therapy. Twenty-four participants with cerebral palsy (CP group) and 35
      non-disabled participants (ND controls) were tested with a dynamometer (OP group:
      mean age 8 years 5 months, 13 males, 11 females; ND group: mean age 8 years 6
      months, 19 males, 16 females). According to the Gross Motor Function
      Classification System (GMFCS), of the 24 participants with CP, eight were at
      level I, six were at level II, and 10 participants were at level III. For the
      spasticity measure, the dynamometer quantified the resistive torque of the hip
      adductors during passive abduction at 4 speeds. The adductor strength test
      recorded a maximum concentric contraction. CP group spasticity was significantly
      reduced following SDR and adductor strength was significantly increased after
      surgery. Both pre- and postoperative values remained significantly less than the
      ND controls. Spasticity results agreed with previous studies indicating a
      reduction. Strength results conflicted with previous literature subjectively
      reporting a decrease following SDR. However, results agreed with previous
      objective investigations examining knee and ankle strength, suggesting strength
      did not decrease following SDR.

PMID- 11995890
TI  - Clinically prescribed orthoses demonstrate an increase in velocity of gait in
      children with cerebral palsy: a retrospective study.
AB  - The purpose of this study was to determine the effect clinically prescribed ankle
      foot orthoses (AFOs) have on the temporal-spatial parameters of gait, as compared
      with barefoot walking in children with cerebral palsy. A retrospective chart
      review of data collected between 1995 and 1999 in our motion analysis laboratory
      was performed. A retrospective chart review of 700 patients revealed 115 patients
      (mean age 9 years) who had a primary diagnosis of CP (diplegia n=97, hemiplegia
      n=18). All were wearing clinically prescribed hinged or solid AFOs at the time of
      undergoing a three dimensional gait analysis. In line with our standard clinical
      practice, data for both conditions (braced and barefoot walking) were collected
      the same day by the same examiner. Statistical analyses indicated the temporal
      and spatial gait parameters of velocity, stride length, step length, and single
      limb stance were significantly increased (p<0.001) with the use of AFOs versus
      barefoot walking. Cadence was the only parameter found to not be statistically
      different.

PMID- 11995891
TI  - Intermittent intensive physiotherapy in children with cerebral palsy: a pilot
      study.
AB  - The aims of the study were: (1) to determine the feasibility of a rehabilitation
      program combining intensive therapy periods (4 times/week for 4 weeks) with
      periods without therapy (8 weeks) over a 6-month period in severely impaired
      children with cerebral palsy (CP); and (2) to measure changes in gross motor
      function after intensive therapy periods (immediate effects) and rest periods
      (retention). A convenient sample included five children (two females, three
      males; mean age 22.6 months [SD 9.9]) with severe forms of CP with impairment of
      four limbs and trunk (GMFCS levels IV and V). A multiple-baseline design was
      used. Changes in motor performance were assessed by a blind evaluator using the
      Gross Motor Function Measure. Visual and statistical analyses followed. Level of
      compliance during intensive therapy was 93.1%. Children received a mean of 30
      treatments over the 24 weeks of the experimental phase compared with the 48
      treatments they would have received routinely. Increases in GMFM scores (mean
      9.2%; range 3 to 15%) were significant in three children (p<0.05) and all
      participants maintained their motor performance during the two 8-week rest
      periods. Results showed that four treatments per week over a 4-week period were
      well tolerated when separated by rest periods. The intermittent program led to
      improvements in motor function that were maintained over the rest periods.
      Results underline the need to reconsider the organization of physical
      rehabilitation programs. A regime that is intensive enough without being tiring
      and one that provides practice conditions for consolidating motor skills learned
      during the intensive therapy period may best optimize motor training.

PMID- 11995892
TI  - Health status of school-aged children with cerebral palsy: information from a
      population-based sample.
AB  - In this study parents' systematic accounts of the health status of 408 school
      aged children with cerebral palsy (CP) are reported (221 males, 187 females; mean
      age 8 years 5 months, SD 1 year 11 months; range 5 to 13 years), as are relations
      between severity of functional motor impairment and eight functional health
      status domains. Data were collected as part of a longitudinal study of the motor
      development of a population-based, stratified, random sample of children with CP
      from across Ontario, Canada. The Gross Motor Function Classification System
      (GMFCS) was used to classify severity of CP and functional health status was
      described with the eight-level Health Utilities Index-Mark 3. Rates of functional
      limitations in Mobility, Dexterity, Speech, and Vision were statistically
      significantly associated with GMFCS levels (all p<0.01), with correlation values
      (tau-b) of 0.82, 0.58, 0.46, and 0.36, respectively. Functional limitations in
      hearing (tau-b=0.16; p=0.04) and cognition (tau-b=0.27; p<0.01) were both
      statistically significantly associated with GMFCS levels, though correlations
      were low. Neither emotion (tau-b=0.03; p=0.24) nor pain (tau-b=0.07; p=0.37) was
      associated with degree of functional limitation as described by the GMFCS.
      Clinical and epidemiological implications of findings are discussed.

PMID- 11995893
TI  - Prevalence of, and risk factors for, physical ill-health in people with Prader
      Willi syndrome: a population-based study.
AB  - The medical findings from a population-based study of Prader-Willi syndrome (PWS)
      are discussed (in which birth incidence of PWS was estimated at 1:22,000 and
      death rate at over 3% per annum). In this study the prevalence of specific
      medical disorders that might account for a shortened life expectancy were
      investigated. Of all people with a possible diagnosis of PWS, only those meeting
      clinical criteria and/or with a confirmed genetic diagnosis were included in the
      study. Sixty-six individuals, 40 males and 26 females with a mean age of 19 years
      (range of 0 to 46 years) agreed to participate in the population-based study
      group. A prevalence rate of 25% for non-insulin dependent diabetes mellitus
      (NIDDM) was found in adults. Mean age at onset was 20 years. Those with NIDDM had
      a higher past maximum body weight and a greater likelihood of positive family
      history. Nearly 50% across the age groups reported a history of recurrent
      respiratory infections. High rates of fractures (29%), leg ulceration (22% in
      adults), sleep disorders (20%), and severe scoliosis (15% in childhood) were also
      reported. It is postulated that hypotonia is a possible contributory factor to
      the risk of strabismus, scoliosis, and respiratory infections. Other causes of
      morbidity, in particular the high rates of NIDDM, may be due to a failure to
      manage over-eating resulting in severe obesity. Early diagnosis and clear
      guidance to families about these risks and how they might be prevented is
      recommended. It is hypothesized that the high pain threshold may result in the
      presence of some illness not being apparent.

PMID- 11995894
TI  - Care of adolescents with severe learning disability from tuberous sclerosis.
AB  - A postal study was completed by 138 members of the Tuberous Sclerosis Association
      for individuals with severe learning disabilities from tuberous sclerosis complex
      (TSC) (78 males, median 20 years of age; 60 females median 19 years 6 months of
      age) to investigate the abilities and care needs of these adolescents and young
      adults. Results were compared with a Salford community survey of young people
      with severe learning disability (SLD) from a variety of causes (42 males, median
      17 years; 29 females, median 17 years 8 months of age). Those with SLD associated
      with TSC had a higher level of verbal disability and were more dependent for
      managing toileting and bathing. The young people with TSC were less able to
      interact socially, showing autistic behaviour. Sexually, they were less aware and
      less active. Only 20 were thought by their parents to have received sex
      education.

PMID- 11995895
TI  - Validity of the Test of Infant Motor Performance for prediction of 6-, 9- and 12
      month scores on the Alberta Infant Motor Scale.
AB  - The Test of Infant Motor Performance (TIMP) is a test of functional movement in
      infants from 32 weeks' post-conceptional age to 4 months postterm. The purpose of
      this study was to assess in 96 infants (44 females, 52 males) with varying risk,
      the relation between measures on the TIMP at 7, 30, 60, and 90 days after term
      age and percentile ranks (PR) on the Alberta Infant Motor Scale (AIMS).
      Correlation between scores on the TIMP and the AIMS was highest for TIMP tests at
      90 days and AIMS testing at 6 months (r=0.67, p=0.0001), but all comparisons were
      statistically significant except those between the TIMP at 7 days and AIMS PR at
      9 months. In a multiple regression analysis combining a perinatal risk score and
      7-day TIMP measures to predict 12-month AIMS PR, risk, but not TIMP, predicted
      outcome (21% of variance explained). At older ages TIMP measures made increasing
      contributions to prediction of 12-month AIMS PR (30% of variance explained by 90
      day TIMP). The best TIMP score to maximize specificity and correctly identify 84%
      of the infants above versus below the 10th PR at 6 months was a cut-off point of
      1 SD below the mean. The same cut-off point correctly identified 88% of the
      infants at 12 months. A cut-off of -0.5 SD, however, maximized sensitivity at
      92%. A negative test result, i.e. score above -0.5 SD at 3 months, carried only a
      2% probability of a poor 12-month outcome. We conclude that TIMP scores
      significantly predict AIMS PR 6 to 12 months later, but the TIMP at 3 months of
      age has the greatest degree of validity for predicting motor performance on the
      AIMS at 12 months and can be used clinically to identify infants likely to
      benefit from intervention.

PMID- 11995896
TI  - Immune mediated chorea encephalopathy syndrome in childhood.
AB  - We report four previously healthy female children, aged between 3 and 8 years,
      who presented with encephalopathy and an extrapyramidal movement disorder (chorea
      n=4, rigidity n=2, oculogyric crisis n=2). In addition, an acute behavioural
      disturbance occurred in two patients and mutism in two others. Seizures heralded
      the onset of the illness in three patients. Acute MRI was either normal or
      initially normal with later generalized cerebral atrophy. All infective
      (including streptococcus), biochemical, and metabolic investigations were normal,
      although all four patients had oligoclonal bands in the (CSF) but not the serum,
      indicating intrathecal immunoglobulin synthesis. All four children made an
      apparently full recovery within four months of the onset. We suggest that these
      patients represent an immune-mediated movement disorder and encephalopathy
      syndrome.

PMID- 11995897
TI  - Stuttering: incidence and causes.

PMID- 11995898
TI  - Benign congenital hypotonia is not a diagnosis.

PMID- 11995899
TI  - Energy consumption in spasticity.

PMID- 11995900
TI  - Pyridoxine treatment in a subgroup of children with pervasive developmental
      disorders.

PMID- 11995901
TI  - Guidelines for school programs to prevent skin cancer.
AB  - Skin cancer is the most common type of cancer in the United States. Since 1973,
      new cases of the most serious form of skin cancer, melanoma, have increased
      approximately 150%. During the same period, deaths from melanoma have increased
      approximately 44%. Approximately 65%-90% of melanomas are caused by ultraviolet
      (UV) radiation. More than one half of a persons lifetime UV exposure occurs
      during childhood and adolescence because of more opportunities and time for
      exposure. Exposure to UV radiation during childhood plays a role in the future
      development of skin cancer. Persons with a history of > or = 1 blistering
      sunburns during childhood or adolescence are two times as likely to develop
      melanoma than those who did not have such exposures. Studies indicate that
      protection from UV exposure during childhood and adolescence reduces the risk for
      skin cancer. These studies support the need to protect young persons from the sun
      beginning at an early age. School staff can play a major role in protecting
      children and adolescents from UV exposure and the future development of skin
      cancer by instituting policies, environmental changes, and educational programs
      that can reduce skin cancer risks among young persons. This report reviews
      scientific literature regarding the rates, trends, causes, and prevention of skin
      cancer and presents guidelines for schools to implement a comprehensive approach
      to preventing skin cancer. Based on a review of research, theory, and current
      practice, these guidelines were developed by CDC in collaboration with
      specialists in dermatology, pediatrics, public health, and education; national,
      federal, state, and voluntary agencies; schools; and other organizations.
      Recommendations are included for schools to reduce skin cancer risks through
      policies; creation of physical, social, and organizational environments that
      facilitate protection from UV rays; education of young persons; professional
      development of staff involvement of families; health services; and program
      evaluation.

PMID- 11995902
TI  - Bite marks and the diagnosis of venomous snakebite.

PMID- 11995903
TI  - Giardiasis as a threat to backpackers in the United States: a survey of state
      health departments.
AB  - Forty-eight of the 50 state health departments in the United States responded to
      a questionnaire about giardiasis in their jurisdictions. The agencies had reports
      of 34348 cases during 1991 and studied 80 outbreaks in the same period. Nineteen
      of these outbreaks were attributed to consumption of contaminated drinking water;
      only two outbreaks were reported among individuals identified as campers or
      backpackers. Only two departments considered water-associated giardiasis to be a
      problem for backpackers in their jurisdiction, and neither had any data to
      support this concern. The surveillance data of health departments indicate that
      giardiasis is a common communicable disease in the United States. They do not,
      however, provide any evidence that wilderness water is an important cause of the
      disease in this country.

PMID- 11995904
TI  - Intestinal coinfection with numerous Giardia trophozoites and Vibrio cholerae in
      hospitalized children with watery diarrhea.
AB  - During the recent cholera epidemic which affected Peru and other Latin American
      countries, fresh stool samples of 100 hospitalized children were assessed
      February through April 1991. The children had been admitted because of profuse
      watery diarrhea. The microbiologic study of wet mount preparations showed curved
      bacteria suspicious for cholera agent and confirmed afterward to be Vibrio
      cholerae 01 scrotype Inaba. In 30% of such cases, besides the curved bacteria, a
      strikingly large number of trophozoites of Giardia intestinalis were observed.
      The same samples studied by permanent stains confirmed the presence of Giardia
      trophozoites. To our knowledge, the association of Giardia with serious epidemic
      cholera infection has not been previously described. All patients were admitted
      because of severe dehydration requiring intravenous fluid replacement, which
      might suggest a synergistic role for the above-noted coinfection. Adequately
      designed case-control studies are needed to ascertain the frequency and the
      pathophysiologic and clinical significance of such an unusual association.

PMID- 11995905
TI  - Effect of body composition on metabolic responses to carbohydrate feeding in
      males during exposure to 8, 12, and 27 degrees C.
AB  - The effect of body composition on thermoregulation in response to a feeding
      regime was evaluated in eight male volunteers (21-27 years of age) during 120 min
      of exposure at 8, 12, and 27degrees C. Subjects were divided with respect to body
      fat [high fat (HF) = 19-28%, N = 4: low fat (LF) = 10-15%, N= 4] and randomly
      assigned the three air temperature conditions twice to examine the thermogenic
      effect of a sequential timed feeding regime of either a carbohydrate (CHO) or
      placebo (PL) beverage during exposure. Tissue insulation (I), rectal temperature
      (T(re)), mean skin temperature (T(sk)), metabolism (M), and respiratory exchange
      ratio (R) were examined. T(re), T(sk), M, and I revealed no significant
      differences between treatment (PL vs. CHO) at any temperature (8, 12, or 27
      degrees C). However, pooled T)(sk) at 27 degrees C, and pooled I at 12 degrees C
      revealed significant (p < .05) differences between the LF and HF groups. In
      addition, at 8, 12, and 27 degrees C, pooled T(re), T(sk), and I decreased (p <
      .05) during the length of exposure, whereas pooled M increased (p < .05) at 8 and
      12 degrees C. Pooled R increased during the length of exposure (p < .05) at 8 and
      12 degrees C and differed (p < .05) between the LF and HF groups at 8 degrees C
      only. From these data, it appears that whereas substrate utilization differed
      between dietary treatment (8 degrees C) and across time (8 and 12 degrees C),
      there was a differential effect between LF and HF groups (T(sk) at 27 degrees C
      and I at 12 degrees C) that was not influenced by feeding regime.

PMID- 11995906
TI  - Bite marks are useful for the differential diagnosis of snakebite in Brazil.
AB  - OBJECTIVE: To assess whether examination of the bite marks could be useful for
      the differential diagnosis between venomous and nonvenomous snakebite. DESIGN:
      Assessment of the validityof the bite marks in the differential diagnosis
      betweenvenomous and nonvenomous snakebite in a series of patients prospectively
      recruited in a 32-month period. SETTING: Teaching hospital in a southeastern
      Brazilian town. PATIENTS: Forty-two victims of snakebite who brought the captured
      or dead snake for identification and who had recognizable bite marks.
      INTERVENTION: Inspection of the bite site, recording the aspect of the marks
      either as isolated fang punctures or as multiple scratch-like teeth marks.
      RESULTS: The presence of isolated fang marks, when related to venomous snakebite,
      had a sensitivity of 100%, a specificity of 56%, and a predictive value of 89%.
      The finding of multiple, scratch-like teeth marks had a predictive value of 100%
      when related to nonvenomous snake bite. CONCLUSIONS: Examination of the bite
      marks showed to be useful for the differential diagnosis between venomous and
      nonvenomous snakebites in Brazil, which has implications for the option of
      empirical administration of antivenin to patients when the snake is not available
      for identification.

PMID- 11995907
TI  - Effect of a face mask on respiratory water loss during sleep in cold conditions.
AB  - The purpose of this study was to test the hypothesis that a heat-and-moisture
      retaining mask would result in a significant decrease in respiratory water loss
      among healthy subjects sleeping in a cold environment. The study was done in a
      backyard near a tertiary-care center during winter nights with ambient
      temperatures of less than 0 degrees C. Subjects were 10 healthy volunteers, 8
      males and 2 females, aged 23-40 years, with a mean of 30.9 years. In a crossover
      design study, subjects slept alone in mountaineering tents on two nights (8 h
      each night) using sleeping bags and ground insulation. On one night, they wore
      heat-and-moisture-retaining masks designed for cold weather exercise. On the
      other night, they wore no mask. Subjects were weighed before and after each
      session to obtain an estimate of respiratory water loss. Comparisons were made of
      weight loss with and without the mask. We found the use of the masks resulted in
      decreased weight loss in all but one subject. The mean reduction in weight loss
      was 0.13 kg (SD +/- 0.18 kg). Using a one-tailed t-test, this difference was
      found to be significant (p < .05). We conclude that the use of a simple and
      inexpensive face mask can result in a meaningful decrease in overnight
      respiratory water loss while sleeping in a cold environment.

PMID- 11995908
TI  - Summary of hunting injuries in central Wisconsin: a 4-year experience at a rural
      referral center.
AB  - Surveillance of hunting-associated injuries was performed over a 4-year period at
      a rural Emergency Department in central Wisconsin. Over that period of time, 125
      individuals sought treatment for hunting-related injuries. The majority of
      injuries were related to autumn deer hunting and included both gun and bow and
      arrow hunting. Over half of the persons injured while hunting with a bow and
      arrow fell from a height. The admission rate for persons in the immediate area
      was 35.1%, but for those from outside the area, it was 64.8%. The effects of the
      referral bias result in severe injuries being seen in rural Emergency Departments
      during hunting seasons, necessitating such departments to be prepared for a wide
      range of injuries.

PMID- 11995909
TI  - Cobras.
AB  - Human encounters with cobras in Africa and Asia are common with substantial
      mortality and primarily respiratory paralysis in untreated cases. First aid
      includes maintaining calm, placing a lymphatic retardant on the bitten extremity,
      and transportation to a medical facility. Medical management is antivenin.
      Physiologic monitoring and the ability to manage the compromised airway are
      important.

PMID- 11995910
TI  - Pulmonary embolism presenting as high-altitude pulmonary edema.
AB  - High-altitude pulmonary edema (HAPE) is a recognized risk of rapid ascent to high
      altitude. Since the recognition of this entity more than 30 years ago, most
      pulmonary deaths at high altitude have been attributed to HAPE. However, as the
      bodies can almost never be recovered for postmortem examination, rare diagnoses
      that appear clinically similar to HAPE will not be recognized. A 33-year-old
      woman climbing on Mt. Everest, and taking oral contraceptive pills, developed
      what seemed to be severe HAPE. Examination after she was evacuated from the
      mountain revealed a deep venous thrombosis in her left leg and multiple pulmonary
      emboli. We propose that multiple pulmonary emboli at high altitude can mimic
      HAPE, and fatal pulmonary embolism may be an explanation for some alleged victims
      of HAPE who died despite what should have been adequate descent.

PMID- 11995911
TI  - Trichuriasis associated to severe transient Coomb's-negative hemolytic anemia and
      macroscopic hematuria.

PMID- 11995912
TI  - Cervical spine injury.

PMID- 11995913
TI  - The Mountain Medicine Institute.

PMID- 11995914
TI  - Recent progress in alpha 1-adrenoceptor pharmacology.
AB  - The adrenoceptors (ARs) play a key role in the modulation of sympathetic nervous
      system activity and are a site of action for many clinically important
      therapeutic agents. The alpha1-adrenoceptor subtypes (alpha1A-, alpha1B-, and
      alpha1D-AR) play a prominent role in regulating vascular tone and hypertrophic
      growth of smooth muscle and cardiac cells. Their functional characteristics with
      respect to ligand binding and second messenger utilization have been well
      described. Here, we review recent progress on subtype-specific subcellular
      localization, participation in signaling cascades, and the pivotal function of
      alpha1-ARs, as delineated through studies on genetically engineered animals.
      Together, these findings will provide new insights into the physiological and
      pathophysiological roles of the alpha1-ARs.

PMID- 11995915
TI  - Glycosylphosphatidylinositol (GPI)-anchored proteins.
AB  - From the numerous studies developed at the last quarter of the 20th century,
      glycosylphosphatidylinositol (GPI) anchor has been established as a unique mode
      of protein binding to the plasma membrane. The core structure of this anchor
      consists of ethanolamine phosphate, trimannoside, glucosamine and inositol
      phospholipid in this order. The anchor is combined with the carboxyl-terminal of
      protein by the ethanolamine head. GPI-anchored proteins are ubiquitously
      distributed among Eucarya from vertebrates to protozoa, and also shown to be
      present in some of Archaeobacteria such as Sulfolobus. There is no evidence for
      the presence of GPI-anchored protein in Eubacteria. In the eucaryotic cells, both
      biosynthesis of GPI precursors and posttranslational protein modification with
      GPI proceed in the endoplasmic reticulum. On GPI modification, the carboxyl
      terminal signal peptide is split off from the protein and the resulting new
      carboxyl-terminal is then combined with the amino group of ethanolamine residue
      in the GPI precursors. The whole process of cleavage and GPI attachment is
      catalyzed by GPI-transamidase complex. Many genes concerning GPI biosynthesis and
      protein modification have been cloned and sequenced. The carboxyl-terminal signal
      peptide containing hydrophobic tail is characterized by genetic analysis and
      shown to be essential for GPI modification of protein. Recent computational
      analysis further clarified the detailed requirement of the carboxyl-terminal
      regions for GPI-anchoring. GPI-anchored proteins are assumed to be transported
      from Golgi to the plasma membrane in the form of "lipid rafts", and expressed as
      the clusters in the cell surface.

PMID- 11995916
TI  - Evaluation of musk by enzyme-linked immunosorbent assay.
AB  - We report the development of enzyme-linked immunosorbent assay (ELISA) for the
      quantitative analysis of a unique musk protein (MP-1) in musk samples. Musk
      defatted with ethyl acetate/methanol (9:1, v/v) was dipped in cold water and
      ammonium sulfate was added to the supernatant up to 85% saturation. The resulting
      precipitate was applied to a Bio-Gel P-100 chromatography. The fraction eluted at
      the void region was collected and it was consecutively purified by affinity
      chromatography on a DEAE Affi-Gel Blue and on anion-exchange columns containing
      DEAE-Sepharose CL-6B. This protein was determined to be homogeneous by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under denaturing
      conditions with an apparent molecular weight of 35000 Da and was called as musk
      protein-1 (MP-1). Polyclonal antibodies of MP-1 were produced by injecting it
      into a rabbit. These antibodies were reactive to the aqueous extract of musk and
      the pure antigen. The ELISA could be applied to detect nano gram quantities of
      the antigen in musk samples. This method made it possible to distinguish musk
      samples from different origins.

PMID- 11995917
TI  - Development of radioimmunoassay for measurement of serum digoxin in digitalized
      patients using novel anti-digoxin antiserum.
AB  - There is an antiserum elicited by digoxin 3'-hemisuccinate-bovine serum albumin
      (BSA) conjugate possessing high specificity for digoxin. Our study focused on
      development of RIA using this novel antiserum for measurement of digoxin in serum
      from digitalized patients. The property of the new antiserum was investigated by
      RIA with digoxin 3'-hemisuccinyl-[3H]leucine. The separation of bound and free
      fractions was performed using a dextran-coated charcoal suspension. The new
      antiserum bound approximately 50% of digoxin 3'-hemisuccinyl-[3H]leucine with a
      final dilution of 1:30000. The intra- and inter-assay coefficients of variation
      were <9% in the range of 0.52-4.17 ng/ml. The mean digoxin concentration in serum
      samples (n=35) from digitalized patients was estimated to be 0.68 ng/ml, which
      was lower than its measurement of digoxin with the commercial antidigoxin BSA
      serum and monoclonal anti-digoxin. It is apparent that the RIA described here has
      sufficient precision. The RIA system was available for the measurement of digoxin
      in serum from digitalized patients.

PMID- 11995918
TI  - A new diagnostic method for chronic hepatitis, liver cirrhosis, and
      hepatocellular carcinoma based on serum metallothionein, copper, and zinc levels.
AB  - Serum metal levels and their ratios are frequently reported to be good signals
      for diagnosing various diseases. These parameters are not always specific to the
      disease, however, it is necessary to use other serum parameters for an exact
      diagnosis. We examined whether the monitoring of these serum parameters such as
      metallothionein, copper, and zinc levels are useful in diagnosing hepatic
      disorders. Metallothionein levels of patients with liver cirrhosis and
      hepatocellular carcinoma were found to be significantly lower than those of
      patients with chronic hepatitis and those of controls. In contrast, copper levels
      of the patients with liver cirrhosis and hepatocellular carcinoma were
      significantly higher than those with chronic hepatitis and controls. Zinc levels
      of the patients with chronic hepatitis and hepatocellular carcinoma were lower
      than those of controls. Using these three parameters, we are introducing a new
      parameter, (Cu/Zn)/MT, by which we can discriminate between patients in the
      [control+miscellaneous diseases+chronic hepatitis] group and those in the [liver
      cirrhosis+hepatocellular carcinomal group. The new parameter does not, however,
      allow us to clearly distinguish between the liver cirrhosis and hepatocellular
      carcinoma groups. Multivariate discriminant analysis was found to be very useful,
      with combinations of two discriminant functions having been designed to
      discriminate both between chronic hepatitis and liver cirrhosis and between liver
      cirrhosis and hepatocellular carcinoma. This method recognizes the differences
      between hepatic disorder, including chronic hepatitis, liver cirrhosis, and
      hepatocellular carcinoma groups. On the basis of these results, we propose here
      that the diagnosis of hepatic disorders should be made based on a combination of
      three serum levels such as those of metallothionein, copper, and zinc.

PMID- 11995919
TI  - Protein kinase C activation by iridal type triterpenoids.
AB  - Eleven iridal type triterpenoids from Iris tectorum and Belamcanda chinensis were
      examined for protein kinase C (PKC) activation and binding activity to PKC. Among
      the tested compounds, nine iridals showed dose-dependent activities, and a mutual
      relation between the two activities was also observed. 28-Deacetylbelamcandal,
      which has been found to be a new class 12-O-tetradecanoylphorbol 13-acetate type
      tumor promoter, showed the most potent activity in both tests. The structural
      requirements of the iridals inducing these activities were as follows: 1) a
      hydrophobic side-chain, 2) an E-methylidene aldehyde group at the C-1 position,
      and 3) a hydroxyl group at the C-26 position.

PMID- 11995920
TI  - Effect of activins AB and B on DNA synthesis stimulated by epidermal growth
      factor in primary cultured rat hepatocytes.
AB  - The effect of activins AB and B on DNA synthesis stimulated by epidermal growth
      factor (EGF) was studied in primary cultured rat hepatocytes and compared with
      the effect of activin A, a suppressor of DNA synthesis. Activin AB inhibited DNA
      synthesis as assessed by [3H]thymidine incorporation. The inhibition by activin
      AB was detected at 6 ng/ml, and the 12.5 ng/ml concentration produced almost
      maximal inhibition, approximately 40%, almost the same as that produced by
      activin A. Inhibition by activin A was detected at 3 ng/ml, and the 6 ng/ml
      concentration produced almost maximal inhibition. Activin B, on the other hand,
      had no effect on DNA synthesis up to 50 ng/ml. The increase in labeling index by
      EGF was also reduced to about 20% by 25 ng/ml activin A and activin AB, but not
      by activin B. Activin B, however, inhibited the binding of [125I]activin A to
      hepatocytes, but had no effect on the inhibition of DNA synthesis by activin A,
      even at 3-fold excess concentrations. These findings suggest that activin AB may
      act in the same manner as activin A does in terms EGF's inhibitory effect on DNA
      synthesis, although the effective concentration is higher than that of activin A.
      The findings also suggest that activin B receptors are present in hepatocytes but
      that they do not mediate signal transduction leading to the inhibition of DNA
      synthesis.

PMID- 11995921
TI  - Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for
      neurosteroids and its inhibition by benzodiazepines.
AB  - In this report, we compared kinetic constants and products in the reduction of
      the neurosteroids, 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha THP) and
      3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC), and their
      precursors, 5alpha-dihydroprogesterone (5alpha-DHP), 5alpha
      dihydrodeoxycorticosterone (5alpha-DHDOC) and progesterone, by three isoenzymes
      (AKR1C1, AKR1C2 and AKR1C3) of human 3alpha-hydroxysteroid dehydrogenase. AKR1C1
      efficiently reduced 3alpha,5alpha-THP, 5alpha-DHP and progesterone to their
      20alpha-hydroxy metabolites, and slowly converted 5alpha-DHDOC to 3alpha,5alpha
      THDOC. AKR1C2 exhibited low 20-ketoreductase activity for 3alpha,5alpha-THP and
      moderate 3-ketoreductase activity for 5alpha-DHP and 5alpha-DHDOC. 3alpha,5alpha
      THDOC was not reduced by the two isoenzymes. No significant activity for the
      steroids was detected with AKR1C3. The results suggest that AKR1C2 is involved in
      the neurosteroid synthesis, but AKR1C1 decreases the neurosteroid concentrations
      in human brain by inactivating 3alpha,5alpha-THP and eliminating the precursors
      from the synthetic pathways. In addition, we found that the several
      benzodiazepines inhibited the three isoenzymes noncompetitively with respect to
      the substrate. Although cloxazolam was a potent and specific inhibitor of AKR1C3,
      diazepam, estazolam, flunitrazepam, medazepam and nitrazepam, that inhibited
      AKR1C1 and AKR1C2, may influence the neurosteroid metabolism.

PMID- 11995922
TI  - Characterization of rat aortic fragment within collagen gel as an angiogenesis
      model; capillary morphology may reflect the action mechanisms of angiogenesis
      inhibitors.
AB  - A fragment of rat thoracic aorta within type I collagen gel was employed as a
      model of angiogenesis, including the processes of cell migration, proliferation
      and capillary tube formation. Endogenous angiogenic factors in this model were
      studied. Expressions of vascular endothelial growth factor (VEGF) and its
      receptor, and proteolytic enzyme activities (matrix metalloprotease-2; MMP-2 and
      plasminogen activator; PA) increased during angiogenesis. The angiogenesis was
      inhibited by VEGF receptor kinase inhibitor and MMP inhibitor, confirming that
      these endogenous factors played an important role in angiogenesis. Interestingly,
      these inhibitors induced different capillary morphologies, including differences
      of cell migration and sprouting. Furthermore, dexamethasone (a down-regulator of
      MMP and PA) and TNP-470 (an endothelial cell growth inhibitor) induced another
      capillary morphology. The results suggest that the capillary structure in this
      model is dramatically influenced by the inhibition of angiogenic signalling and
      extracellular matrix (ECM) degradation. We also found that a novel angiogenesis
      inhibitor, the microbial metabolite luminacin, which was recently identified by
      us (Wakabayashi et al., J. Antiobiot., 53, 591-596 (2000)), induced a different
      morphology compared with other inhibitors examined, suggesting that it has a
      unique mechanism of action. Our results indicate that this rat aorta model should
      be useful for screening novel angiogenesis inhibitors.

PMID- 11995923
TI  - Natural trans-crotonin: the antiulcerogenic effect of another diterpene isolated
      from the bark of Croton cajucara Benth.
AB  - The nor-clerodane diterpene trans-crotonin isolated from the bark of Croton
      cajucara BENTH. was investigated for its ability to prevent the formation of
      gastric-mucosa ulceration in different experimental models in mice. The results
      obtained from crotonin were compared with those obtained with another diterpene,
      DHC (trans-dehydrocrotonin) in the same models. When previously administered
      (p.o.) at the dose of 100 mg/kg, crotonin, as well as DHC, significantly reduced
      (p<0.05) gastric injury induced by stress (72, 67%), indomethacin/bethanechol
      (78, 29%) and pylorus ligature (35, 30%). In the HCl/ethanol-induced gastric
      ulcer model, at oral doses of 100 and 250 mg/kg, crotonin significantly prevented
      (p<0.05) the formation of gastric lesions by 51 and 56%, respectively, when
      compared to the control group. Gastric injury was also of significantly less
      magnitude in the DHC treatment group (p<0.05). In the pylorus-ligature model,
      crotonin (p.o.), like cimetidine, increased the volume of gastric juice when
      compared to the control group (p<0.05). No significant modifications where found
      in gastric parameters such as pH or total acid content after oral crotonin
      treatment. However, systemic alterations were observed when crotonin (100 mg/kg)
      was previously administered intraduodenally to mice. We observed significant
      changes (p<0.001) in gastric-juice parameters such as an increase in volume and a
      decrease in gastric acidity. Those pre-treated with crotonin as well as with DHC
      did not increase free mucus production (p>0.05). The results suggest that
      crotonin presents a significant anti-ulcer effect when assessed in these ulcer
      induced models. As with DHC, the antiulcerogenic effects of crotonin are probably
      related to anti-secretory or/and gastroprotective properties of this substance.
      In light of results obtained with DHC and natural trans-crotonin in the present
      study, we concluded that the A-ring of both diterpenes is not directly involved
      in the antiulcerogenic activity.

PMID- 11995925
TI  - Induction of p16INK4a transcription and of cellular senescence by aclacinomycin
      derivatives and cardiac glycosides.
AB  - Stable transformants of Saos-2 cells that contain the luciferase reporter gene
      under the control of the human p16INK4a transcriptional regulatory region were
      established, and were used to identify growth-inhibiting substances from culture
      broths of actinomycetes and extracts of plants. Among the active substances so
      far identified were an aclacinomycin-derivative, cenerubin B, and a cardiac
      glycoside, periplocin. These substances inhibited growth of normal human
      fibroblasts, and induced senescent phenotypes including a flattened morphology
      and increased acidic beta-galactosidase activity, although the activities of
      their derivatives to induce p16CDKN2 and beta-galactosidase did not coincided
      with each other. These results suggest that the reporter system using the
      p16CDKN2 transcriptional regulatory region is a useful means for screening growth
      inhibiting substances that are potential anti-tumor agents.

PMID- 11995924
TI  - Possible role of ginsenoside Rb1 on regulation of rat liver triglycerides.
AB  - We have studied the effects of ginsenoside Rb1 (GRb1) on the change in lipid
      contents in rat liver. When GRb1 was administered intraperitoneally to rats,
      liver microsomal cytochrome P-450 content and NADPH-cytochrome P-450 reductase
      activity were lower than those in control rats. The contents of triglyceride (TG)
      and cholesterol were decreased, but those of total phospholipid,
      phosphatidylcholine, and phosphatidylethanolamine were increased in the GRb1
      treated group compared with controls. These results indicate that GRb1 might be
      involved in lipid metabolism by regulating the activity of microsomal cytochrome
      P-450 monooxygenase. Although liver TG levels were reduced by GRb1, the levels of
      TG and beta-lipoprotein in serum from the GRb1-treated group did not change as
      compared with those in controls. Thus we suggest that the decrease in liver TG
      levels with GRb1-treatment is not associated with the secretion of TG-rich very
      low-density lipoprotein. Furthermore, the level of cAMP was also significantly
      increased in the GRb1-treated group as compared with that in controls.
      Additionally, the cAMP level was more markedly increased as compared with that in
      the GRb1-treated group or control group when GRb, was exogenously added to the
      reaction system for measuring cAMP production in homogenates from control group
      liver. Accordingly, these results demonstrate that GRb1 might lower TG levels via
      cAMP-production in the liver, and GRb1 might be an interesting candidate to for a
      modulator of cAMP-mediated effects, especially within the liver steatosis system.

PMID- 11995926
TI  - Activation of the aryl hydrocarbon receptor by methyl yellow and related
      congeners: structure-activity relationships in halogenated derivatives.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates the biological action of many environmental compounds. Methyl
      yellow (4-dimethylaminoazobenzene; MY) is a principal azo-dye, and structurally
      related compounds were subjected to analysis of structure-activity relationships
      as AhR ligands by using a yeast AhR signaling assay. The effects of halogen
      substitution among 23 halogenated MYs on the AhR ligand activity can be
      summarized as follows: enhancement by halogen-substitution at the ortho-position
      (2'- and 6'-position), and reduction by substitution at the para-position (4'
      position). The greatest enhancement of the ligand activity was observed in 2',6'
      dichlorinated MY (13.5-fold of MY), and its AhR ligand activity was very close to
      that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the present assay system.
      In the study of compounds structurally related to MY, benzanilide (BA) showed
      almost the same AhR ligand activity as azobenzene and trans-stilbene.
      Furthermore, 4'-chlorobenzanilide, in which the length of the molecule is similar
      to that of MY, enhanced the AhR ligand activity by ortho(2')-chlorine
      substitution, and the AhR ligand activity of 2',4'-dichlorobenzanilide was
      similar to that of 2'-chloro-MY. These results suggest that the amide bond is
      equivalent to the -N=N- or -CH=CH- double bond for recognition as the ligand by
      AhR in 1,2-diphenyl-1,2-ene derivatives.

PMID- 11995928
TI  - Molecular cloning and functional expression of cDNAs encoding oxidosqualene
      cyclases from Costus speciosus.
AB  - Costus speciosus produces a large quantity of steroidal glycosides derived from
      the sole aglycone, diosgenin. Cycloartenol, a product of oxidosqualene cyclase
      (OSC), is postulated to be a common intermediate for phytosterols of primary
      metabolism and diosgenin of secondary metabolism, possibly providing a metabolic
      branch point. Two cDNAs, CSOSC1 and CSOSC2, were cloned from C. speciosus by RT
      PCR and cDNA library screening. Both cDNAs encode 759 amino acids with high
      mutual identity (74%), resembling (>55% identity) the known OSCs. Phylogenetic
      tree analysis indicated that the gene products occupy distinct positions from
      those of cycloartenol synthases (CASs) and triterpene synthases from
      dicotyledonous plants. By functional expression in yeast, CSOSC1 and CSOSC2 were
      proved to encode a CAS and a multifunctional triterpene synthase, respectively.
      The present result is the first demonstration of the functional expression of
      OSCs from monocotyledonous plants.

PMID- 11995929
TI  - Anti-inflammatory and cytotoxic activities of five Veronica species.
AB  - Biological activities of five Veronica species (Scrophulariaceae), V. cymbalaria,
      V. hederifolia, V. pectinata var. glandulosa, V. persica and V. polita were
      studied for their anti-inflammatory and cytotoxic activities. Their methanol
      extracts showed both the inhibitory activity of nitric oxide (NO) production in
      lipopolysaccharide (LPS)-stimulated macrophages and cytotoxic activity against KB
      epidermoid carcinoma and B16 melanoma. When the methanol extracts were
      fractionated between water and chloroform, water fractions significantly
      inhibited NO production without any cytotoxicity, while chloroform fractions
      showed cytotoxicity dose-dependently. When the radical scavenging activity was
      determined using 2,2-diphenyl-1-picryl-hydrazyl (DPPH), water fractions of the
      five Veronica species scavenged free radicals effectively, suggesting that the
      inhibitory effect of this species on NO production was due to their radical
      scavenging activity. On the other hand, chloroform fractions of Veronica species
      except for V. cymbalaria showed similar cytotoxic activity against KB and B16
      melanoma cells.

PMID- 11995930
TI  - Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the
      Turneraceae as a new source of antiulcerogenic drugs.
AB  - Turnera ulmifolia is a plant belonging to the family Turneraceae, popularly known
      in Brazil as chanana. This species is distributed from Guyana to southern Brazil
      where it is considered a weed. The plant occurs in tropical rain forest, fields,
      and gardens. Chanana tea is used in Brazilian folk medicine for the treatment of
      diseases related mainly to gastric dysfunction including gastric and duodenal
      ulcers. In this study, the ability of a lyophilized infusion, as an aqueous
      fraction (AqF) of the aerial parts of T. ulmifolia, was investigated for its
      ability to prevent ulceration of the gastric and duodenal mucosa was examined in
      mice and rats, respectively. The AqF significantly reduced the formation of
      lesions associated with HCl/ethanol administration by 39% and 46%, respectively,
      at doses of 500 mg/kg and 1000 mg/kg, p.o. The AqF also significantly reduced the
      incidence of gastric lesions induced by a combination of indomethacin and
      bethanechol by 58% and 72% at doses of 500 mg/kg and 1000 mg/kg, respectively. In
      stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at
      doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively (p<0.05). A pyloric
      ligature experiment showed that the highest dose of the AqF significantly
      affected the gastric juice parameters by increasing the pH from 2.5 (control) to
      5.3 and decreasing the acid output from 11.3 (control) to 3.7 mEq/ml/4 h. The AqF
      had no significant effect on duodenal ulcers induced by cysteamine. Preliminary
      phytochemical screening confirmed that flavonoids were the major constituents of
      the AqF of T. ulmifolia. These results indicate that this extract has a
      significant antiulcerogenic effect, as popularly believed.

PMID- 11995931
TI  - Role of the lipid emulsion on an injectable formulation of lipophilic KW-3902, a
      newly synthesized adenosine A1-receptor antagonist.
AB  - KW-3902 (a newly synthesized adenosine A1-receptor antagonist) has potent
      diuretic and renal protective activities. We investigated the influence of the
      emulsion formulation on the pharmacokinetics of KW-3902 and its metabolite (M1)
      in rats using three different formulations, i.e., a lipid emulsion about 130 nm
      in diameter composed of egg yolk lecithin: soybean oil: oleic acid=1:1:0.048, a
      liposome about 100 nm in diameter composed of egg yolk lecithin, and a saline
      solution containing 1% (v/v) each of dimethyl sulfoxide and 1 N NaOH. There was
      no significant difference in the pharmacokinetic parameters of KW-3902
      (elimination half-life (T1/2), area under the plasma concentration-time curves
      (AUC0-infinity), total body clearance (CL), mean residence time (MRT) and volume
      of distribution at steady-state (Vdss) and M1 (Cmax, T1/2, AUC0-infinity and MRT)
      after injection of these three dosage forms. Moreover, we investigated in vitro
      the binding of KW-3902 to blood components using these three formulations. KW
      3902 was completely partitioned into the blood components regardless of its
      dosage form. These findings suggested that KW-3902 dissociated rapidly from the
      lipid emulsion or liposome in blood after injection and showed intrinsic
      pharmacokinetics of KW-3902 at doses of 0.1 and 1 mg/kg. Thus, the lipid emulsion
      formulation of KW-3902 was defined as a solvent, which was a vehicle for
      dissolving the drugs to prepare the injection, at its expected effective doses.

PMID- 11995933
TI  - Preventive effects of Impatiens balsamina on the hen egg-white lysozyme (HEL)
      induced decrease in blood flow.
AB  - Monitoring the blood flow of unanesthesized mice was found to be a reliable and
      effective method for studying their anaphylactic responses, in addition to the
      known method of monitoring blood pressure. Hen egg-white lysozyme (HEL)-specific
      anaphylaxis in mice was estimated by monitoring the decrease in blood flow with a
      Doppler blood flow meter. This method is convenient for searching for both
      anaphylaxis and anti-anaphylactic substances from natural products. Using this
      system, we estimated the anti-anaphylactic effects of the 35% ethanol extract
      (IB) of petals of Impatiens balsamina L., as well as those of anti-allergic
      agents currently used. Kaempferol 3-rutinoside and lawsone from IB significantly
      inhibited the decrease of blood flow. We also found that platelet-activating
      factor (PAF) and serotonin participate in decreasing the blood flow, but
      histamine does not.

PMID- 11995927
TI  - In vitro antiinflammatory activity of kalopanaxsaponin A isolated from Kalopanax
      pictus in murine macrophage RAW 264.7 cells.
AB  - In the present study, effects of various hederagenin monodesmosides isolated from
      the stem bark of Kalopanax pictus Nakai, such as hederagenin, 5-hederin,
      kalopanaxsaponin A, kalopanaxsaponin 1, and sapindoside C, have been evaluated on
      lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and
      tumor necrosis factor-alpha (TNF-alpha) release by the macrophage cell line RAW
      264.7. Among the tested monodesmosides, kalopanxsaponin A was the most potent
      inhibitor of NO production, and it also significantly decreased PGE2 and TNF
      alpha release. Consistent with these observations, the expression level of
      inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzyme was inhibited by
      kalopanxsaponin A in a concentration-dependent manner. Thus, this study suggests
      that kalopanaxsaponin A-mediated inhibition of iNOS, COX-2 expression, and TNF
      alpha release may be one of the mechanisms responsible for the anti-inflammatory
      effects of the stem bark of Kalopanax pictus Nakai.

PMID- 11995932
TI  - In vitro screening for antitumour activity of Clinopodium vulgare L. (Lamiaceae)
      extracts.
AB  - Aqueous extract of Clinopodium vulgare L. showed strong antitumour activity when
      tested in vitro on A2058 (human metastatic melanoma), HEp-2 (epidermoid
      carcinoma, larynx, human) and L5178Y (mouse lymphoma) cell lines-6 h after
      treatment disintegration of the nuclei and cell lysis started. Applied at a
      concentration of 80 microg/ml it reduced the cell survival to 1.0, 5.6 and 6.6%,
      respectively. The concentrations of aqueous extract inhibiting the growth of
      A2058, HEp-2 and L5178Y cells by 50% (IC50 values) were calculated to be 20, 10
      and 17.8 microg/ml respectively. Two groups of active substances were detected:
      the first one, probably combining glycosides, influenced adhesion, while the
      second one caused massive cell vacuolisation. The chloroform extract, which
      contained ursolic acid and gentriacontan had also cytotoxic, however a little bit
      weaker effect. All changes observed were irreversible.

PMID- 11995934
TI  - Progressive development of the osteoblast phenotype during differentiation of
      osteoprogenitor cells derived from fetal rat calvaria: model for in vitro bone
      formation.
AB  - Osteoblasts are the primary cells responsible for bone formation and are thought
      to originate from mesenchymal osteoprogenitor cells within skeletal tissues. To
      elucidate the osteoblastic differentiation process, fetal rat calvariae (FRC)
      were enzymatically digested and fractionated to provide an osteoprogenitor
      enriched cell population. The third fraction of cells from the five sequential
      digestions tested showed a significant osteogenic response to dexamethasone
      (Dex), a well-known differentiation hormone, which was demonstrated by high
      alkaline phosphatase activity early in culture and enhanced calcium deposition
      and bone nodule formation in late stage cultures. These data indicate that
      fraction three contains a large number of osteoprogenitor cells. During the
      osteoblastic differentiation of the third fraction of FRC cells, the formation of
      collagen cross-links (pyridinoline and deoxypyridinoline) was time-dependently
      accelerated with the accumulation of collagens, which coincided with an onset of
      mineralization of the cultures, i.e., calcium deposition and bone nodule
      formation. Moreover, noncollagenous matrix proteins, bone sialoprotein and
      osteocalcin, were also increased at both mRNA and protein level in Dex-treated
      cultures with advancing culture periods. Further examination for mRNA expression
      of bone morphogenetic proteins (BMPs) and TGF-beta1 revealed a notable elevation
      in BMP-6 mRNA expression on days 3 and 10, and no significant change in TGF-beta1
      expression. These observations suggested that the progressive formation of
      collagen cross-links, production of noncollagenous proteins, and up regulation of
      BMP-6 mRNA play an important role in the osteoblastic differentiation process of
      osteoprogenitor cells isolated from FRC. This culture system provides us a
      suitable model for in vitro bone formation.

PMID- 11995935
TI  - Protective effect of fleroxacin against the nephrotoxicity of isepamicin in rats.
AB  - The protective effect of fleroxacin on isepamicin-induced nephrotoxicity was
      investigated. Wistar rats were administered either fleroxacin 100 mg/kg orally,
      isepamicin 300 mg/kg subcutaneously, or fleroxacin and isepamicin in combination
      for 14 d. The animals given 300 mg/kg of isepamicin showed a significant increase
      in urine N-acetyl-beta-D-glucosaminidase (NAG) levels as compared with the
      control animals which received saline (p<0.01). However, the increase in NAG
      level was markedly less when isepamicin was administered in combination with
      fleroxacin (p<0.01). Fleroxacin alone had no effect on urine NAG activity. Serum
      creatinine and blood urea nitrogen (BUN) levels were significantly higher in
      animals treated with isepamicin alone than in the control animals (p<0.01) or
      animals receiving the isepamicin fleroxacin combination (p<0.01).
      Histopathologically, fleroxacin induced very few cellular alterations, but
      considerably reduced the manifestation of typical signs of isepamicin
      nephrotoxicity. This investigation demonstrates that fleroxacin protects animals
      against isepamicin-induced nephrotoxicity.

PMID- 11995936
TI  - Preventive effects of chlorophyllin fixed on chitosan towards DNA adduct
      formation of 3-amino-1-methyl-5H-pyrido [4,3-b]indole in CDF1 mice.
AB  - Chlorophyllin, a water-soluble derivative of chlorophyll, is known to suppress
      the mutagenic and carcinogenic action of compounds having polycyclic structures,
      e.g., heterocyclic amines and aflatoxin B1. Recently, we reported that
      chlorophyllin fixed on chitosan (chl-chitosan), which is insoluble in water, can
      efficiently and tightly trap these heterocyclic amines. We have studied whether
      this adsorption to chl-chitosan can result in an interference with DNA-adduct
      formation caused by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a
      heterocyclic amine, in CDF1 mice, in which Trp-P-2 had been shown to induce
      hepatocellular carcinomas. Mice were fed a diet containing Trp-P-2 with or
      without chl-chitosan. After 3 d of feeding, DNA-adduct formation in liver and
      lung was examined by 32P-postlabeling analysis. Adducts formed from Trp-P-2 were
      significantly decreased by the chl-chitosan addition (p<0.05, t-test). These
      results suggest that the uptake of Trp-P-2 into the mouse was lowered by its
      adsorption to chl-chitosan, either within the digestive tract or within the food
      itself. This trapping agent, chl-chitosan, is thus worthy of study for cancer
      chemoprevention.

PMID- 11995937
TI  - Effects of Kangen-karyu on coagulation system and platelet aggregation in mice.
AB  - Kangen-karyu (KGK) is a herbal formula created under the theory of traditional
      Chinese herbal medicine to invigorate the blood and dispel blood stasis. It
      contains 6 herbs: peony root, cnidium rhizome, safflower, cyperus rhizome,
      saussurea root (JP XIV), and Salvia miltiorrhiza root. The present study has been
      conducted to evaluate the in vivo anti-thrombotic activity of KGK using normal
      mice. Three consecutive days of oral administration of KGK to mice significantly
      extended tail-bleeding time and suppressed ex vivo platelet aggregation, while it
      did not extend the prothrombin time of plasma. It was revealed that the anti
      thrombotic effects of KGK did not depend on the downregulation of the coagulation
      system, but depended in part on the inhibition of platelet aggregation. These
      results explain one of the pharmacological activities of KGK to invigorate the
      blood and dispel blood stasis.

PMID- 11995938
TI  - Anti-diabetic activity of alcoholic extract of Celosia argentea Linn. seeds in
      rats.
AB  - Celosia argentea Linn. commonly known as "Cocks Comb" and its seeds are widely
      used in Indian folk medicine for the treatment of diabetes mellitus. This study
      was undertaken to evaluate the effect of an alcoholic extract of Celosia argentea
      seeds (ACAS) on blood glucose and body weight in alloxan-induced diabetic rats.
      ACAS was found to reduce the increase of blood glucose in alloxan-induced
      diabetic rats (27.8% at 250 mg/kg and 38.8% at 500 mg/kg body weight). Chronic
      administration of ACAS significantly (p<0.01) reduced the blood glucose in
      alloxan-induced diabetic rats for two weeks. Also the extract prevented a
      decrease in body weight in alloxan-induced diabetic rats. These results suggest
      that the ACAS possesses anti-diabetic activity in alloxan-induced diabetic rats.

PMID- 11995939
TI  - Effect of cationic liposomes in an in vitro transcription and translation system.
AB  - The effects of cationic liposomes complexed with plasmid DNA on the process of
      transcription was examined using a recently developed rapid cell free translation
      system. The findings indicate that the liposome itself inhibited the process when
      the ratio of DNA/liposome typically used in transfection studies was used.

PMID- 11995940
TI  - Pharmacokinetic interactions between carbamazepine and the traditional Chinese
      medicine Paeoniae Radix.
AB  - The present study was conducted to evaluate the effects of Paeoniae Radix (PR),
      one of the most famous tonic traditional Chinese medicines, on the
      pharmacokinetics of carbamazepine (CBZ) in rats and to determine the possible
      interactions between PR and CBZ. The significant decrease in Tmax indicated that
      simultaneous oral administration of PR contributed to more rapid absorption of
      CBZ. It is suggested that the faster absorption of CBZ might lead to the rapid
      onset of its clinical effect. There were no significant differences in maximum
      concentration (Cmax), area under the plasma concentration-time curve (AUC), half
      life (t1/2), mean residence time (MRT), clearance/bioavailability (CL/F), and
      apparent volume of distribution/bioavailability (Vd/F) of CBZ between the two
      groups, showing that PR did not significantly affect the absorption extent,
      distribution, metabolism, and elimination of CBZ. A significant decrease in
      protein binding rate was found when CBZ was coadministered with PR. Further
      studies are in progress to clarify the clinical significance and the mechanism
      underlying the effects of PR on the protein binding of CBZ observed in the
      present study.

PMID- 11995941
TI  - Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph
      node Th-1/Th-2 proportion.
AB  - We have already reported that the D-Fraction, a beta-glucan extracted from the
      fruiting body of the maitake mushroom (Grifola frondosa), activates cellular
      immunity and expresses anti-tumor effects. In this study we investigated the anti
      tumor functions of D-Fraction in relation to its control of the balance between T
      lymphocyte subsets Th-1 and Th-2. D-Fraction decreased the activation of B cells
      and potentiated the activation of helper T cells, resulting in enhanced cellular
      immunity. It also induced the production of interferon (IFN)-gamma, interleukin
      (IL)-12 p70, and IL-18 by whole spleen cells and lymph node cells, but suppressed
      that of IL-4. These results suggest that D-Fraction establishes Th-1 dominance
      which induces cellular immunity in the population that was Th-2 dominant due to
      carcinoma.

PMID- 11995942
TI  - The effect of tablet formulation and hardness on in vitro release of cephalexin
      from Eudragit L100 based extended release tablets.
AB  - Eighteen batches of cephalexin extended release tablet were prepared by wet
      granulation method by using Eudragit L100. The effect of the concentration of
      Eudragit L100, microcrystalline cellulose and tablet hardness on cephalexin
      release was studied. The formulated tablets were also characterized for physical
      and chemical parameters. The dissolution results showed that a higher amount of
      Eudragit in tablet composition and higher tablet hardness resulted in reduced
      drug release. An increased amount of microcrystalline cellulose in tablet
      composition resulted in enhanced drug release. Tablet composition of 13.3% w/w
      Eudragit L100 and 6.6 to 8% w/w microcrystalline cellulose with hardness of 7-11
      kg/cm2 gave predicted release for 6 h. The in vitro release was compared with a
      marketed tablet. Physical and chemical parameters of all formulated tablets were
      within acceptable limits. The effect of storage on in vitro release and
      physicochemical parameters of tablets was evaluated and two batches among
      formulated eighteen batches found to be in acceptable limits.

PMID- 11995943
TI  - Medicinal plants in the healing of dry socket in rats: microbiological and
      microscopic analysis.
AB  - The effectiveness of medicinal herbs as antimicrobial agents was tested on
      isolated microorganisms from an induced alveolitis and on alveolitis in rats.
      Sixteen ethanolic extracts from plants were prepared and tested. The plant
      materials were selected from ethnobotanic data and the best result was obtained
      with Schinus terebinthifolius Raddi. The activity on Enterococcus, Bacillus
      corineforme, Streptococcus viridans and S. beta-hemolytic was better than the one
      presented by the antibiotic currently used for the treatment of alveolitis. The
      extract of Schinus terebinthifolius Raddi has shown good wound-healing activity
      by histological analysis.

PMID- 11995944
TI  - Modulatory effects of garlic extracts on proliferation of T-lymphocytes in vitro
      stimulated with concanavalin A.
AB  - Different active components from the garlic (Allium sativum) possess
      immunomodulatory activity both in vitro and in vivo. However, mechanisms of their
      actions are not sufficiently elucidated. In this study we examined the effects of
      garlic aqueous extract (GAE) and garlic ethanolic extract (GEE), prepared from
      two different garlic powder samples, on proliferation of rat thymocytes and
      splenocytes in culture, stimulated with concanavalin A (Con A). It has been shown
      that the extracts from both samples significantly modulate lymphocyte
      proliferation, triggered by this potent T-cell mitogen, depending on the type and
      dilutions of extracts and concentrations of Con A. The extracts, alone, were not
      mitogenic for lymphocytes. Generally, higher concentrations of the extracts
      showed inhibitory effects, whereas lower concentrations significantly augmented
      proliferation of lymphocytes. The stimulatory effect of GAE was stronger using
      splenocytes and suboptimal concentrations of Con A as a consequence of increased
      interleukin 2 (IL-2) production as well as the expression of IL-2 receptor alpha
      (IL-2Ralpha). The relationship between these two phenomena was demonstrated using
      neutralizing anti-IL-2Ralpha monoclonal antibody. The inhibitory effect of GAE
      correlated with a decrease in IL-2 production, but was not followed by down
      regulation of IL-2Ralpha expression. The addition of IL-2 almost completely
      abolished inhibition of lymphocyte proliferation in the presence of higher
      concentrations of GAE.

PMID- 11995945
TI  - Anti-ulcerogenic and analgesic activities of the leaves of Wilbrandia ebracteata
      in mice.
AB  - Wilbrandia ebracteata (Cogn.) Cogn. is a medicinal plant belonging to the
      Cucurbitaceae family used popularly as an antiulcer and analgesic medicine. The
      hydromethanol extract of leaves was investigated to determine its anti
      ulcerogenic (ethanol and indomethacin induced gastric damage) and analgesic
      (writhing and tail-flick tests) activities in mice (efficacy), its acute toxicity
      (safety), and its phytochemistry (quality control). Oral administration of leaf
      extract at a dose of 1000 mg/kg body wt. significantly reduced 73.3% of the total
      area of lesion in ethanol-induced gastric damage, but was inactive in an
      indomethacin-induced gastric damage test. The hydromethanol extract was also
      inactive in both analgesic tests. Oral administration of the leaf extract did not
      produce mortality in mice, while the LD50 value of the roots was 22.10 mg/kg body
      wt. in female mice and 58.31 mg/kg body wt. in male mice. Leaves of W. ebracteata
      reacted positively for steroids, flavonols, flavanones, saponins, tannins and
      xanthones and negative for other compounds, including cucurbitacins. Leaf extract
      of W. ebracteata was active as an anti-ulcerogenic, probably through increasing
      gastric defensive factors, and flavonoids might be the main constituent
      responsible for this activity.

PMID- 11995946
TI  - Antinociceptive, anti-inflammatory and acute toxicity effects of Zhumeria majdae
      extracts in mice and rats.
AB  - Antinociceptive and anti-inflammatory effects and acute toxicity of aqueous
      infusion and ethanolic maceration extracts of the aerial parts of Zhumeria majdae
      were studied in mice and rats. Antinociceptive activity was determined using hot
      plate and writhing tests. The effect of the extracts against acute inflammation
      was studied by acetic acid increased vascular permeability and xylene-induced ear
      edema in mice. The activity of the extracts against chronic inflammation was
      assessed using the cotton pellet test in rats. LD50 values of the infusion and
      maceration extracts were 3.09 g/kg body wt., and 3.94 g/kg body wt.,
      respectively. Phytochemical screening of the extracts indicated the presence of
      flavonoids and tannins. In the hot-plate test, the intraperitoneal injection of
      both extracts showed significant and dose-dependent antinociceptive activity in
      mice. Naloxone, an opioid antagonist, on pretreatment inhibited the
      antinociceptive activity of the extracts. The extracts exhibited antinociceptive
      activity against acetic acid-induced writhing, which was partially blocked by
      naloxone. Both extracts showed significant effect against acute inflammation
      induced by acetic acid in mice. In the chronic inflammation test, efficacy of the
      extracts was similar to that of baclofen and dexamethasone in rats. It is
      concluded that the aqueous infusion and ethanolic maceration extract of the
      aerial parts of Zhumeria majdae have antinociceptive effects and this may be
      mediated by opioid receptors. The extracts also showed anti-inflammatory effects
      against acute and chronic inflammation.

PMID- 11995947
TI  - Antiplasmodial activity of aspidosperma indole alkaloids.
AB  - The antiplasmodial activity of twelve alkaloids with an aspidospermane skeleton
      was estimated in vitro on chloroquine-resistant and sensitive strains of
      Plasmodium falciparum. Seven tetracyclic alkaloids possessing a free ethyl chain
      such aspidospermine, showed IC50 after incubation for 72 h between 3.2 and 15.4
      microM. Moreover, four pentacyclic alkaloids with ethyl chain included in a
      tetrahydrofuran, such haplocine, showed a reduced activity, with IC50, after 72
      h, between 22.6 and 52.6 microM. According to these results, a chloroquine
      potentiating experiment was also performed with two of the most active compounds.
      Isobolograms were obtained and demonstrated a synergic effect of N-formyl
      aspidospermidine and aspidospermine when associated with chloroquine. The
      cytotoxicity and the selectivity index of some alkaloids were also estimated.

PMID- 11995948
TI  - Structure-antiemetic-activity of some diarylheptanoids and their analogues.
AB  - The structure-activity relationship of diarylheptanoids and their analogues
      inhibitory of emesis induced by copper sulfate in young chicks was investigated
      by testing 19 compounds. The compounds are 5 diarylheptanoids isolated from
      Alpinia katsumadai (Zingiberacea), 5 chemical derivatives of them, 6 analogues
      isolated from Zingiber officinale rhizome (Zingiberaceae), and 3 analogues
      available on the market. Among them, two types of essential functional structure
      of diarylheptanoids and their analogues showed the inhibitory effects against
      emesis.

PMID- 11995949
TI  - Evaluation of antioxidant properties of root bark of Hemidesmus indicus R. Br.
      (Anantmul).
AB  - Hemidesmus indicus R. Br. (Asclepiadaceae) is a well known drug in Ayurveda
      system of medicine. In the present study, antioxidant activity of methanolic
      extract of H. indicus root bark was evaluated in several in vitro and ex vivo
      models. Further, preliminary phytochemical analysis and TLC fingerprint profile
      of the extract was established to characterize the extract which showed
      antioxidant properties. The in vitro and ex vivo antioxidant potential of root
      bark of H. indicus was evaluated in different systems viz. radical scavenging
      activity by DPPH reduction, superoxide radical scavenging activity in
      riboflavin/light/NBT system, nitric oxide (NO) radical scavenging activity in
      sodium nitroprusside/Greiss reagent system and inhibition of lipid peroxidation
      induced by iron-ADP-ascorbate in liver homogenate and phenylhydrazine induced
      haemolysis in erythrocyte membrane stabilization study. The extract was found to
      have different levels of antioxidant properties in the models tested. In
      scavenging DPPH and superoxide radicals, its activity was intense (EC50 = 18.87
      and 19.9 microg/ml respectively) while in scavenging NO radical, it was moderate.
      It also inhibited lipid peroxidation of liver homogenate (EC50 = 43.8 microg/ml)
      and the haemolysis induced by phenylhydrazine (EC50 = 9.74 microg/ml) confirming
      the membrane stabilization activity. The free radical scavenging property may be
      one of the mechanisms by which this drug is effective in several free radical
      mediated disease conditions.

PMID- 11995950
TI  - Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal
      and diabetic rats and mice.
AB  - Alpha-glucosidase inhibitors are oral antidiabetic drugs. A traditional Chinese
      medical herb, Sangzhi (Ramulus mori), appears to have properties similar to those
      of alpha-glucosidase inhibitors. The effects of an aqueous extract of Shangzhi
      (SZ) were studied in normal and alloxan diabetic rats and mice, and these results
      compared with those for acarbose, an alpha-glucosidase inhibitor. In our grade
      dose studies, SZ was found to lower and prolong the zenith of blood glucose
      concentration (ZBG) after sucrose or starch loading and stabilize blood glucose
      levels in fasting normal and alloxan diabetic mice. After 2 weeks of SZ
      administration with high-calorie chow or a normal diet, the fasting and non
      fasting blood glucose concentrations in alloxan diabetic mice and rats were
      decreased. In alloxan rats, the blood fructosamine concentration was lowered.
      Results for acarbose and SZ were similar. These indicate that SZ has alpha
      glucosidase inhibitory effects.

PMID- 11995951
TI  - Effect of Withania somnifera glycowithanolides on a rat model of tardive
      dyskinesia.
AB  - Withania somnifera glycowithanolides (WSG) were investigated for their preventive
      effect on the animal model of tardive dyskinesia (TD), induced by once daily
      administration of the neuroleptic, haloperidol (1.5 mg/kg, i.p.), for 28 days.
      Involuntary orofacial movements (chewing movements, tongue protusion and buccal
      tremors) were assessed as TD parameters. WSG (100 and 200 mg, p.o.), administered
      concomitantly with haloperidol for 28 days, inhibited the induction of the
      neuroleptic TD. Haloperidol-induced TD was also attenuated by the antioxidant,
      vitamin E (400 and 800 mg/kg, p.o.), but remained unaffected by the GABA-mimetic
      antiepileptic agent, sodium valproate (200 and 400 mg/kg, p.o.), both agents
      being administered for 28 days like WSG. The results indicate that the reported
      antioxidant effect of WSG, rather than its GABA-mimetic action, may be
      responsible for the prevention of haloperidol-induced TD.

PMID- 11995952
TI  - Effect of bioactive tannoid principles of Emblica officinalis on ischemia
      reperfusion-induced oxidative stress in rat heart.
AB  - The tannoid principles of the fruits of Emblica officinalis have been reported to
      exhibit antioxidant activity in vitro and in vivo. In the present study, an
      emblicanin-A (37%) and -B (33%) enriched fraction of fresh juice of Emblica
      fruits (EOT) was investigated for antioxidant activity against ischemia
      reperfusion (IRI)-induced oxidative stress in rat heart. Vitamin E (VE) was used
      as the standard antioxidant agent. IRI was induced in isolated rat heart by
      perfusing it with modified Kreb-Hensleitt's solution for 5 min, followed by a
      period of ischemia (stoppage of perfusion) for 10 min and then restoring the
      perfusion (reperfusion) for 15 min. IRI induced a significant decrease in the
      activities of cardiac superoxide dismutase, catalase and glutathione peroxidase,
      with a concomitant increase in lipid peroxidation. These IRI-induced effects were
      prevented by the administration of EOT (50 and 100 mg/kg body wt.) and VE (200
      mg/kg body wt.) given orally twice daily for 14 days prior to the sacrifice of
      the animals and initiation of the perfusion experiments. The study confirms the
      antioxidant effect of E. officinalis and indicates that the fruits of the plant
      may have a cardioprotective effect.

PMID- 11995953
TI  - In vitro anti-HIV and antitumor evaluation of Amazonian plants belonging to the
      Apocynaceae family.

PMID- 11995954
TI  - Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.)
      Merr in climacteric symptomatology: a multicentric, open, prospective and non
      randomized trial.
AB  - A multicentric, open, prospective, observational and no-randomized clinical trial
      was carried out in Spain with 190 postmenopausal women receiving a soy
      preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg
      isoflavones). The main object of the present study was to investigate its
      efficacy in alleviating the symptomatology derived from the lack of estrogen,
      mainly hot flushes, but also other symptoms such as sleep disorder, anxiety,
      depression, vaginal dryness, loss of libido and bone pain. Each patient received
      35 mg isoflavones per day in two doses. During the four months' treatment, a
      statistically significant decrease in the number of hot flushes with PHYTO SOYA
      was experienced by 80.82% women; only 5,48% patients did not improve with the
      treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes.
      All the other studied parameters also showed a statistically significant
      decrease. No severe side-effects were reported and tolerance was excellent.
      Treatment with PHYTO SOYA resulted in a significant improvement of the
      symptomatology that accompanies the lack of estrogen during menopause.

PMID- 11995955
TI  - Effects of Choto-san on hemorheological factors and vascular function in stroke
      prone spontaneously hypertensive rats.
AB  - Choto-san is a formula used for the treatment of headache and vertigo. Recently
      it has often also been used for hypertension and dementia. One of the mechanisms
      involved is thought to be the improvement of blood circulation, but the details
      are still unclear. In this study, the effect of Chotosan was studied on nitric
      oxide (NO) function, hemorheological factors and endothelial function in stroke
      prone spontaneously hypertensive rats (SHR-SP). Rats were given Choto-san in
      drinking water for eight weeks. Body weight, blood pressure, serum NO2-/NO3-,
      lipid peroxides, blood viscosity, erythrocyte deformability and endothelium
      dependent/-independent relaxation were measured. The results indicated that Choto
      san caused a decrease in blood pressure and an increase in erythrocyte
      deformability and NO function. Blood viscosity was not changed. Furthermore,
      endothelium-dependent relaxation by acetylcholine was significantly increased as
      compared to control. In this study, it was supposed that Choto-san had a
      protective effect on the endothelium. SHR-SP is a useful model for human brain
      stroke, and Choto-san showed a protective effect against cerebral vascular injury
      in the susceptible rat.

PMID- 11995956
TI  - The evaluation of the radioprotective effect of Triphala (an ayurvedic
      rejuvenating drug) in the mice exposed to gamma-radiation.
AB  - The effect of 0, 5, 6.25, 10, 12.5, 20, 25, 40, 50 and 80 mg/kg b. wt. of aqueous
      extract of triphala (an Ayurvedic herbal medicine) administrered
      intraperitoneally was studied on the radiation-induced mortality in mice exposed
      to 10 Gy of gamma-radiation. Treatment of mice with different doses of triphala
      consecutively for five days before irradiation delayed the onset of mortality and
      reduced the symptoms of radiation sickness when compared with the non-drug
      treated irradiated controls. The highest protection against GI (gastrointestinal)
      death was observed for 12.5 mg/kg triphala, where a highest number of survivors
      were reported up to 10 days post-irradiation. While 10 mg/kg triphala i.p.
      provided the best protection as evidenced by the highest number of survivors
      after 30 days post-irradiation in this group when compared with the other doses
      of triphala. Toxicity study showed that triphala was non-toxic up to a dose of
      240 mg/kg, where no drug-induced mortality was observed. The LD50 dose i.p. of
      triphala was found to be 280 mg/kg b. wt. Our study demonstrates the ability of
      triphala as a good radioprotective agent and the optimum protective dose of
      triphala was 1/28 of its LD50 dose.

PMID- 11995957
TI  - Vanishing cerebellum in myelomeningocoele.
AB  - Reduced hindbrain herniation observed after intrauterine myelomeningocoele repair
      suggests that posterior fossa changes in myelomeningocoele are secondary results
      of prolonged prenatal spinal cerebrospinal fluid leak. Exceptionally, this
      transforaminal herniation results in 'degeneration' of cerebellar tissue,
      presumably due to mechanically induced ischaemia. This phenomenon was called
      'vanishing cerebellum in Chiari II malformation'. We report three similar cases
      of this apparently rare finding. Pregnancies were normal. Cerebellar hypoplasia
      was already recognized in one instance by prenatal ultrasound at gestational week
      25. Postnatal imaging was similar in all three patients showing small posterior
      fossa, beaked midbrain tectum, small brainstem without pontine prominence,
      reduced cerebellar tissue with virtual absence of one hemisphere and
      supratentorial hydrocephalus. Our series is too small to draw firm conclusions
      about predisposing risk factors for and consequences of vanishing cerebellum.
      Cerebellar damage can interfere with cognitive development, as shown in children
      with cerebellar agenesis/ hypoplasia, congenital ataxia and small cerebellum
      following prematurity. A final conclusion on the cognitive consequence of
      vanishing cerebellum cannot be drawn on the available literature and our limited
      observations, as one of our patients died at 3 months and another is still too
      young for appropriate testing. However, the third (aged 15 years) is very
      severely retarded.

PMID- 11995958
TI  - Congenital Guillain-Barre syndrome associated with maternal inflammatory bowel
      disease is responsive to intravenous immunoglobulin.
AB  - A 34-week floppy preterm infant born to a mother with acute ulcerative colitis
      presented with a progressive reduction in spontaneous limb movements, severe
      generalized hypotonia, areflexia, autonomic dysfunction and respiratory failure.
      Electromyography revealed pronounced denervation activity and markedly slow nerve
      conduction velocity (3 m/s) with evidence of conduction block. These findings
      indicated demyelination with additional axonal features. The infant was diagnosed
      with congenital Guillain-Barre syndrome, was treated with intravenous
      immunoglobulin and showed clinical improvement within 48 hours of treatment. The
      relationship between inflammatory bowel syndrome and inflammatory demyelinating
      polyneuropathy is discussed.

PMID- 11995959
TI  - White matter abnormalities in Leber's hereditary optic neuropathy due to the 3460
      mitochondrial DNA mutation.
AB  - Leber's hereditary optic neuropathy is a maternally inherited disorder
      characterized by acute or subacute loss of central vision leading to severe optic
      atrophy. It is caused by mutations in the mitochondrial genome. Primary mutations
      are located at nucleotide positions 3460, 11778 and 14484 in genes encoding
      subunits of complex I of the respiratory chain. The occurrence of a demyelinating
      disease such as multiple sclerosis has been reported mainly in females with the
      11778 mutation. We report a patient with Leber's hereditary optic neuropathy,
      kyphosis and white matter lesions in association with the 3460 mtDNA mutation. It
      is suggested that multiple sclerosis-like illness and deformities of the
      vertebral column may be associated pathogenically with Leber's hereditary optic
      neuropathy.

PMID- 11995960
TI  - Association of the congenital bone marrow failure syndromes with retinopathy,
      intracerebral calcification and progressive neurological impairment.
AB  - We present a child with Fanconi anaemia and congenital hypopituitarism, who
      developed intracerebral calcifications, progressive spasticity and retinopathy.
      The chromosome fragility with mitomycin C was increased in both the patient and
      his sibling, confirming a diagnosis of Fanconi anaemia. Aplastic anaemia in
      association with intracerebral calcifications has been described in patients with
      dyskeratosis congenita and Revesz syndrome, but not so far in confirmed cases of
      Fanconi anaemia. This case further illustrates the greater overlap of associated
      features in congenital bone marrow failure syndromes. It also indicates that
      Fanconi anaemia should be actively excluded where such associated features are
      found.

PMID- 11995961
TI  - Gene table: neuronal ceroid lipofuscinoses.

PMID- 11995962
TI  - Cajal-Retzius and subplate neurons: their role in cortical development.
AB  - Cajal-Retzius (C-R) neurons and their processes form a synaptic network in the
      marginal zone of the early telencephalon prior to the arrival of the first wave
      of radial migration of neuroblasts from the subventricular zone. Their origin is
      not yet proved but may be either the medial ganglionic eminence or the
      mesencephalic neuromere. These bipolar or multipolar neurons populate the
      molecular layers of both the fetus and the adult, though sparse in the adult.
      Their thick axon emits collaterals that make synaptic contact with pyramidal
      neurons initially in layer 6 and later within all layers. C-R neurons produce
      GABA, possibly ACh, several calcium-binding proteins (e.g. calmodulin;
      parvalbumin; possibly calretinin), several neuropeptides and are rich in
      ribosomes. Subplate neurons, beneath the cortical plate, emit pioneer axons in
      the incipient formation of the internal capsule and also commissural fibres of
      the early hippocampus. C-R cells express products of the genes reelin, LIS1 and
      DS-CAM, that mediate radial neuroblast migration and lamination of the cortical
      plate and are important in the pathogenesis of lissencephaly. In addition to
      forming the first intrinsic synaptic circuits of the cortical plate and its first
      afferent and efferent connections with subcortical structures, they may play
      additional roles in the formation of ocular dominance columns, in regulating
      neuronogenesis and in cortical repair. They do not later disappear by apoptosis
      as we previously thought, but their functional role in the mature brain is
      unknown.

PMID- 11995963
TI  - Outcome in shunted hydrocephalic children.
AB  - The purpose of the present study was to identify the main risk factors for poor
      outcome in children with shunted hydrocephalus, including the timing of the
      operation. The medical records of patients born between 1984 and 1992, who had
      undergone shunt operation for hydrocephalus before 1994, were analysed
      retrospectively. The following data were collected: aetiology of hydrocephalus,
      other pathology in addition to hydrocephalus, timing of drain implantation,
      number and indication of revisions and several outcome parameters such as school
      type, seizures and morbidity parameters. Children with a post-haemorrhagic
      hydrocephalus fared poorly. Children with hydrocephalus due to spina bifida or
      another congenital malformation had considerably better outcome scores. Pathology
      in addition to hydrocephalus negatively influenced the prognosis. Regarding the
      timing of drain implantation, we found a poorer mental and linguistic development
      in children operated more than 1 month after diagnosis. Patients with more than
      two revisions seem to have a higher chance of developing seizures. In conclusion,
      this study confirms earlier reports that peri- and postnatal haemorrhage is an
      important risk factor for poor outcome. More importantly, we found that delay in
      surgical treatment might also be a risk factor for poor outcome in hydrocephalic
      children.

PMID- 11995964
TI  - Mechanisms of plasmid stable maintenance with special focus on plasmid addiction
      systems.
AB  - The stable inheritance of bacterial plasmids is achieved by a number of different
      mechanisms. Among them are resolution of plasmid oligomers into monomers, active
      plasmid partitioning into dividing cells and selective killing of plasmid-free
      segregants. A special focus is given to the last mechanism. It involves a stable
      toxin and an unstable antidote. The antidotes neutralize their cognate toxins or
      prevent their synthesis. The different decay rates of the toxins and the
      antidotes underlie molecular mechanisms of toxin activation in plasmid-free
      cells. By eliminating of plasmid-free cells from the population of plasmid
      bearing ones the toxin-antidote couples therefore act as plasmid addiction
      systems.

PMID- 11995965
TI  - Saccharomyces cerevisiae--a model organism for the studies on vacuolar transport.
AB  - The role of the yeast vacuole, a functional analogue of the mammalian lysosome,
      in the turnover of proteins and organelles has been well documented. This review
      provides an overview of the current knowledge of vesicle mediated vacuolar
      transport in the yeast Saccharomyces cerevisiae cells. Due to the conservation of
      the molecular transport machinery S. cerevisiae has become an important model
      system of vacuolar trafficking because of the facile application of genetics,
      molecular biology and biochemistry.

PMID- 11995966
TI  - Anaerobic growth of Saccharomyces cerevisiae alleviates the lethal effect of
      phosphotyrosyl phosphatase activators depletion.
AB  - Saccharomyces cerevisiae homologues of phosphotyrosyl phosphatase activator
      (PTPA) are encoded byRRD1 and RRD2, genes whose combined deletion is synthetic
      lethal. Previously we have shown that the lethality of rrd1,2delta can be
      suppressed by increasing the osmolarity of the medium. Here we show that the
      lethality of rrd1,2delta is also suppressed under oxygen-limited conditions. The
      absence of respiration per se is not responsible for the suppression since
      elimination of the mitochondrial genome or a block in heme biosynthesis fail to
      rescue the rrd1,2delta double mutation.

PMID- 11995967
TI  - The effect of methotrexate on actin and invasiveness of hepatoma Morris 5123
      cells in culture.
AB  - Monomeric (G), total (T) and filamentous (F) actin and the state of actin
      polymerisation (F:G) were determined and actin filaments were visualized in
      hepatoma Morris 5123 cells cultured in the presence of methotrexate (MTX) at
      various concentration. The exposure of the cells to this drug resulted in a
      decrease of total and polymerised actin in cytoplasm and in some changes in actin
      filament organization. This coincided with a decrease of the cells' ability to
      migrate through Matrigel coated filters and with inhibition of tumour formation
      after reimplantation of the methotrexate treated cells to experimental rats.

PMID- 11995968
TI  - Antisense hairpin loop oligonucleotides as inhibitors of expression of multidrug
      resistance-associated protein 1: their stability in fetal calf serum and human
      plasma.
AB  - Multidrug resistance-associated protein (MRP1) is a transmembrane pump protein
      responsible for the efflux of chemotherapeutic drugs, an important cause of
      anticancer treatment failure. Trying to circumvent MRP-mediated resistance we
      designed and synthesized hairpin loops forming antisense
      oligodeoxyribonucleotides (ODNs), both phosphodiesters (PO-ODNs) and their
      phosphorothioate analogues (PS-ODNs), to reduce the protein expression by
      targeting its mRNA in a sequence specific manner. Melting temperature
      measurements as well as polyacrylamide gel electrophoresis supported the
      preferential formation of a secondary structure, which was expected to protect
      ODNs against 3'-exonuclease degradation. ODNs and PS-ODNs designed in this work
      were successfully tested as antisense inhibitors of the expression of MRP1 in the
      leukaemia HL60/ADR cell line. Foreseeing the necessity to perform clinical
      studies with such ODNs we investigated their stability against the 3'-exonuclease
      activity of fetal calf serum and human plasma. Under the conditions,
      corresponding to physiological ones, we observed high stability of hairpin loop
      forming ODNs, especially those containing longer (e.g. 7 base pair) stems.
      Comparative studies on the stability of chemically unmodified hairpin loop
      forming ODNs and their PS-counterparts indicated that endonuclease activity did
      not play any important role in the process of their nucleolytic degradation. Our
      studies provide strong evidence for high stability of chemically unmodified
      hairpin loop ODNs, making them an attractive alternative to phosphorothioate
      analogues commonly used in antisense strategy.

PMID- 11995969
TI  - Combined delivery of an antiangiogenic protein (angiostatin) and an
      immunomodulatory gene (interleukin-12) in the treatment of murine cancer.
AB  - We investigated the feasibility of a novel therapeutic approach to treat
      neoplastic diseases in mice. This novel strategy consists in delivering a protein
      (angiostatin) with strong antiangiogenic properties, followed by administration
      of the interleukin 12 gene that is strongly immunomodulatory and has also some
      antiangiogenic effects. When angiostatin-mediated antiangiogenic therapy was used
      in combination with intratumor delivery of the IL-12 gene (a strategy much safer
      than IL-12 protein administration), this produced a synergistic therapeutic
      effect.

PMID- 11995970
TI  - Activity of glycogen depolymerizing enzymes in extracts from brain tumor tissue
      (anaplastic astrocytoma and glioblastoma multiforme).
AB  - An approximately threefold increase in glycogenolytic activity of the neutral
      alpha-1,4-glucosidase and a twofold increase in the same activity of the acid
      isoform have been found in extracts of anaplastic astrocytoma and glioblastoma
      multiforme tumors of brain tissue. "Maltase activity" of the respective enzymes
      increased by 60-80% in both kinds of tumor extracts. However a significant
      decrease in a-amylase and almost complete disappearance of phosphorylase
      activities have also been found in both kinds of tumors.

PMID- 11995971
TI  - Methods of peptide conformation studies.
AB  - In solution most of the peptides assume multiple flexible conformations.
      Determination of the dominant conformers and evaluation of their populations is
      the aim of peptide conformation studies, in which theoretical and experimental
      methods play complementary roles. Molecular dynamics or Monte Carlo methods are
      quite effective in searching the conformational space accessible to a peptide but
      they are not able to estimate, precisely enough, the populations of various
      conformations. Therefore, they must be supplemented by experimental data. In this
      paper, a short review of the experimental methods, most widely used in peptide
      conformational studies, is presented. Among them NMR plays the leading role.
      Valuable information is also obtained from hydrogen exchange, fluorescence
      resonance energy transfer, and circular dichroism measurements. The advantages
      and shortcomings of these methods are discussed.

PMID- 11995972
TI  - Micro-capillary liquid chromatography Fourier transform ion cyclotron resonance
      mass spectrometry--a powerful tool for peptide and protein identification.
AB  - In order to be able to study complex biological samples, a micro-capillary liquid
      chromatography system was coupled to a 9.4 T Fourier transform ion cyclotron
      resonance mass spectrometer. The setup was tested on a tryptic digest of bovine
      serum albumin, which resulted in high sequence coverage (> 92%) of the protein.

PMID- 11995973
TI  - Evolutionary principles for generating protein mimetics: directed assembly of
      peptide loops on topological templates.
AB  - A novel methodology for the reversible competitive condensation of peptide loops
      to chemoreactive topological templates is presented.

PMID- 11995974
TI  - Mass spectrometric analysis of head-to-tail connected cyclic peptides.
AB  - Tandem mass spectrometry is an extremely useful tool for high sensitive sequence
      identification of peptides. In the case of cyclic peptides fragmentation can
      easily be performed for sequence analysis. However, analysis is usually tedious
      due to the lack of a defined beginning and end of the sequence. Since cyclic
      peptides are a highly interesting class of compounds especially for the
      pharmaceutical industry, ways have to be found to identify their strictures. In
      this work we demonstrate how software and dedicated analytical strategies can be
      used for detailed analysis of these substances.

PMID- 11995975
TI  - Supported liquid membrane extraction of peptides.
AB  - The application of supported liquid membrane (SLM) extraction for the enrichment
      of short peptides is presented. The extraction efficiency is dependent on the pH
      of donor phase and salt concentration in acceptor phase. Moreover, the extraction
      efficiency is also influenced by the peptide amino-acid sequence and
      hydrophobicity.

PMID- 11995976
TI  - Enhanced microdialysis of neuropeptides.
AB  - An enhanced microdialysis method for neuropeptides is described and some
      preliminary results of this novel approach are presented. The enhancement is
      achieved by adding a vehicle (solid support) to the perfusion fluid in order to
      increase the diffusion coefficient across the membrane and efficiently transport
      the analytes towards the detector. The microdialysis samples are desalted and
      then analyzed on an electrospray ionization orthogonal time-of-flight mass
      spectrometer. The preliminary results show major increase in signal when
      comparing this new approach of microdialysis with ordinary microdialysis.

PMID- 11995977
TI  - DALDA analogues containing alpha-hydroxymethylamino acids.
AB  - To evaluate the role of aromatic amino-acids residues, four analogues of the mu
      selective opioid peptide agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) containing the
      amphiphilic, a,a-disubstituted amino acid (R)- or (S)-alpha-hydroxymethyltyrosine
      (HmTyr) in position 1 and (R)- or (S)-alpha-hydroxymethylphenylalanine (HmPhe) in
      position 3 of the peptide sequence were synthesized. Only the [(R)-HmPhe3)]DALDA
      analogue displayed full agonistic activity in both the guinea pig ileum and the
      mouse vas deferens assays and turned out to be a delta receptor-selective opioid
      agonist.

PMID- 11995978
TI  - Detection and sequencing of new cyclic peptides from linseed by electrospray
      ionization mass spectrometry.
AB  - Extract of Linum usitatissimum seeds was analyzed by ESI-MS and ESI-MS/MS. The
      analysis confirms the presence of previously reported cyclolinopeptides: CLA
      (c(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val) and CLB (c(Pro-Pro-Phe-Phe-Val-Ile-Met
      Ile-Leu)). Cyclolinopeptides CLD and CLE, which contain methionine oxide, were
      detected in small quantities only. These peptides likely result from the
      oxidation of their precursors, not reported previously: CLD' (c(Pro-Phe-Phe-Trp
      Ile-Met-Leu-Leu)) and CLE'(c(Pro-Leu-Phe-Ile-Met-Leu-Val-Phe)), present at higher
      concentrations in unoxidized extract. Two new cyclic octapeptides: CLF (c(Pro-Phe
      Phe-Trp-Val-Met-Leu-Met)) and CLG (c(Pro-Phe-Phe-Trp-Ile-Met-Leu-Met)) were
      detected and their sequences were proposed on the basis of CID experiments and
      similarity with those of CLD'.

PMID- 11995979
TI  - Conformational stability of six truncated cHMG1a proteins studied in their
      mixture by H/D exchange and electrospray ionization mass spectrometry.
AB  - The high mobility group (HMG) proteins are abundant non-histone components of
      eukaryotic chromatin. The presence of C-terminal acidic tails is a common feature
      of the majority of HMG proteins. Although the biological significance of the
      acidic domains is not clear, they are conferring conformational and metabolic
      stability to the proteins in vitro. Moreover, the length and net charge of the
      acidic tails affect the strength of HMG protein interaction with DNA. Synthesis
      of an insect HMG protein by standard recombinant technology in bacteria leads to
      a mixture of the intact protein (cHMG1a-(1-113) (I)) and a series of its
      degradation products truncated at the C tail: cHMG1a-(1-111) (II); cHMG1a-(1-110)
      (III); cHuMGla-(1-109) (IV); cHMG1a-(1-108) (V); cHMG1a-(1-107) (VI); cHMG1a-(1
      106) (VII). The proteins differ from each other only by the number of amino-acid
      residues at the C-terminal tail. We used H/D exchange mass spectrometry to
      characterize the stability of the proteins directly in their mixture. The results
      show that the proteins I-V and VII have very similar conformations. The protein
      VI is less compact and exchanges its protons faster than the others. It may be
      concluded that the C-terminal tail influences the conformation of the cHMG1a
      protein and that individual residues in this part of the protein play a key role
      in its compactness.

PMID- 11995980
TI  - Evaluation of high temperature glycation of proteins and peptides by electrospray
      ionization mass spectrometry.
AB  - Recently Boratynski & Roy (Glycoconjugate J., 1998, 15, 131) described a fast and
      convenient procedure for the synthesis of glycoconjugates. In the present study
      we used ESI-MS and circular dichroism as tools to analyze non-enzymatic glycation
      products of proteins and peptides. We discuss influence of reaction conditions on
      the rate of glycation of lysozyme. We analyze for the first time collision
      induced dissociation spectra of the obtained peptide conjugates.

PMID- 11995981
TI  - Synthesis and application of chiral triazine condensing reagents prepared from
      esters of amino acids.
AB  - Treatment of cyanuric chloride with chiral amines or esters of chiral amino acids
      gave chiral 2,4-dichloro-6-alkylamino-1,3,5-triazines (2-5) in 49-69% yield,
      which were found useful as coupling reagents. Enantioselective activation and
      enantioselective aminolysis in the presence of 2-5 was observed.

PMID- 11995982
TI  - Design, synthesis and biological evaluation of a new bridged immunosuppressor.
AB  - A bridged peptide with the sequence: H-Thr-Pro-Gln-Arg-Gly-Asp-Val-gamma-Abu-Asn
      Asp-Gln-Glu-Glu-Thr-Thr-Gly-Val-Val-Ser-Thr-Pro-Leu-Ile-Arg-Asn-Gly-OH was
      designed to mimic the discontinuous epitope of the HLA-DQ molecule that might
      interact with CD4. The bridged peptide revealed distinct suppressory effect in
      the humoral immune response. This result supports our suggestion that the 164-172
      region of the HLA-DQ molecule may enhance its interactions with coreceptors,
      possibly with CD4.

PMID- 11995983
TI  - Search for new synthetic immunosuppressants II. Tetrazole analogues of
      hymenistatin I.
AB  - Linear and cyclic hymenistatin I (HS I) analogues with dipeptide segments Ile2
      Pro3 Pro3-Pro4 and Val6-Pro7 replaced by their tetrazole analogues Ile2-psi[CN4]
      Ala3', Pro3-psi[CN4]-Ala4 and Val6-psi[CN4]-Ala7 were synthesized by the solid
      phase peptide synthesis method and cyclized with the TBTU and/or HATU reagent.
      The peptides were examined for their immunosuppressive activity in the lymphocyte
      proliferation test (LPT).

PMID- 11995984
TI  - Novel nociceptin analogues.
AB  - A series of new nociceptin analogues containing cysteine was tested for their
      nociceptive effects in tail-flick test on mice after icv injection. The cysteines
      were introduced in order to get irreversibly binding analogues based on the
      assumption that the cysteines in the ligand can interact with the cysteines from
      the receptor to form an S-S bridge. In vivo tests revealed that Cys1-nociceptin
      (1-13)-NH2 (Cys1-NC) is an antagonist, whereas Cys7-NC is an agonist. Gly1[Phe(p
      NO2)]4-NC was less active indicating that the antagonist properties of Cys1-NC
      are associated with the presence of the sulfhydryl group of cysteine. The
      analogues D-Cys2 and Cys3 were also almost inactive.

PMID- 11995985
TI  - A novel cis-peptide bond motif inducing beta-turn type VI. The synthesis of
      enkephalin analogues modified with 4-aminopyroglutamic acid.
AB  - A new pathway leading to a mixture of four isomers of 4-aminopyroglutamic acid is
      described. Michael type addition of Z-deltaAla-OMe to enolates prepared from
      acylaminomalonates, followed by hydrolysis and decarboxylation give protected 4
      aminopyroglutamic acid with the cis:trans ratio approximately 3:2. This mixture
      was incorporated into Leu-enkephalin (position 2-3). After separation of peptides
      it appeared that all analogues were essentially inactive in guinea pig ileum and
      mouse vas deferens bioassays.

PMID- 11995986
TI  - Synthesis and binding properties of deltorphin I analogues containing (R) and (S)
      alpha-hydroxymethylnaphtylalanine.
AB  - New analogues of deltorphin I (DT I), in which the phenylalanine residue in
      position 3 is substituted with amphiphilic alpha,alpha-disubstituted amino acid
      enantiomers, (R) and (S)-alpha-hydroxymethylnaphtylalanine, were synthesized and
      tested for mu and delta opioid receptor affinity and selectivity. Although both
      analogues have lower affinity to delta receptors than DT I, they both expressed
      specificity to delta receptors.

PMID- 11995987
TI  - Acetylation of methyl 5-amino-1H-[1,2,4]triazole-3-carboxylate.
AB  - Acetylation with acetic anhydride of methyl 5-amino-1H-[1,2,4]triazole-3
      carboxylate, one of the hetareneamino acids, was studied using HPLC, H NMR, FTIR
      and GC-MS. The compound has a significantly decreased susceptibility to
      acetylation compared to 5-amino-1H-[1,2,4]triazole itself. Two isomeric
      diacetylated products were found.

PMID- 11995988
TI  - Novel side reactions accompanying activation and aminolysis of N-benzoyl-2
      alkylserines.
AB  - 2-Phenyl-4-alkyl-4-hydroxymethyl-1,3-oxazolones (2a-d) have been identified as
      side products accompanying activation of N-benzoyl-2-alkylserines (1a-d).
      Oxazolones 2a-d in the presence of amine rearrange subsequently to corresponding
      4-alkyl-2-phenyl-4,5-dihydro-1,3-oxazole-5 carboxylic acids (4a-d) at a 20-68%
      yield.

PMID- 11995989
TI  - Conformational properties of N',N'-dimethylamides of N-acetyldehydroalanine and N
      acetyl-(Z)-dehydrophenylalanine.
AB  - Conformational preferences of Ac-deltaAla-NMe2 and Ac-(Z)-deltaPhe-NMe2 were
      studied and compared with those of their monomethyl counterparts as well as with
      those of their saturated analogues. X-Ray data and energy calculations revealed a
      highly conservative conformation of the dehydro dimethylamides, which is located
      in a high-energy region of the Ramachandran map.

PMID- 11995990
TI  - Hematological and antifungal properties of temporin A and a cecropin A-temporin A
      hybrid.
AB  - Temporin A (TA) and a cecropin A-temporin A hybrid peptide (CATA) were
      synthesized and assayed for their hemolytic, anticoagulant, and antifungal
      properties. CATA retains significant antifungal activity, is less hemolytic than
      TA, and inhibits blood coagulation. These results recommend further studies of
      the biological activities of CATA.

PMID- 11995991
TI  - Antibacterial peptides of the moth Galleria mellonella.
AB  - The work describes purification and biochemical characterization of two inducible
      antimicrobial peptides from the hemolymph of Galleria mellonella. The peptides
      were isolated by a sequence of reversed-phase chromatography steps from the
      hemolymph of larvae immunized with viable bacteria. The first peptide is a member
      of the cecropin family while the second one is rich in proline residues and has a
      unique sequence.

PMID- 11995992
TI  - Influence of organic solvents on papain kinetics.
AB  - Papain activity was studied in water-organic solvent mixtures using the
      fluorogenic substrate Dabcyl-Lys-Phe-Gly-Gly-Ala-Ala-Edans. The increase of
      organic solvent (MeOH, EtOH, iPrOH, TFE, MeCN, (MeO)2Et and DMF) concentration in
      the mixture caused a substantial decrease the initial rate of papain-catalyzed
      hydrolysis. Moreover, the number of papain active sites decreased with the
      increase of DMF and MeOH concentration.

PMID- 11995993
TI  - Signal transmission via G protein-coupled receptors in the light of rhodopsin
      structure determination.
AB  - G protein-coupled receptors (GPCRs) transducing diverse external signals to cells
      via activation of heterotrimeric GTP-binding (G) proteins, estimated to mediate
      actions of 60% of drugs, had been resistant to structure determination until
      summer 2000. The first atomic-resolution experimental structure of a GPCR, that
      of dark (inactive) rhodopsin, thus provides a trustworthy 3D prototype for
      antagonist-bound forms of this huge family of proteins. In this work, our former
      theoretical GPCR models are evaluated against the new experimental template.
      Subsequently, a working hypothesis regarding the signal transduction mechanism by
      GPCRs is presented.

PMID- 11995994
TI  - 3D domain swapping, protein oligomerization, and amyloid formation.
AB  - In 3D domain swapping, first described by Eisenberg, a structural element of a
      monomeric protein is replaced by the same element from another subunit. This
      process requires partial unfolding of the closed monomers that is then followed
      by adhesion and reconstruction of the original fold but from elements contributed
      by different subunits. If the interactions are reciprocal, a closed-ended dimer
      will be formed, but the same phenomenon has been suggested as a mechanism for the
      formation of open-ended polymers as well, such as those believed to exist in
      amyloid fibrils. There has been a rapid progress in the study of 3D domain
      swapping. Oligomers higher than dimers have been found, the monomer-dimer
      equilibrium could be controlled by mutations in the hinge element of the chain, a
      single protein has been shown to form more than one domain-swapped structure, and
      recently, the possibility of simultaneous exchange of two structural domains by a
      single molecule has been demonstrated. This last discovery has an important
      bearing on the possibility that 3D domain swapping might be indeed an
      amyloidogenic mechanism. Along the same lines is the discovery that a protein of
      proven amyloidogenic properties, human cystatin C, is capable of 3D domain
      swapping that leads to oligomerization. The structure of domain-swapped human
      cystatin C dimers explains why a naturally occurring mutant of this protein has a
      much higher propensity for aggregation, and also suggests how this same mechanism
      of 3D domain swapping could lead to an open-ended polymer that would be
      consistent with the cross-beta structure, which is believed to be at the heart of
      the molecular architecture of amyloid fibrils.

PMID- 11995995
TI  - Structure of small G proteins and their regulators.
AB  - In recent years small G proteins have become an intensively studied group of
      regulatory GTP hydrolases involved in cell signaling. More than 100 small G
      proteins have been identified in eucaryotes from protozoan to human. The small G
      protein superfamily includes Ras, Rho Rab, Rac, Sarl/Arf and Ran homologs, which
      take part in numerous and diverse cellular processes, such as gene expression,
      cytoskeleton reorganization, microtubule organization, and vesicular and nuclear
      transport. These proteins share a common structural core, described as the G
      domain, and significant sequence similarity. In this paper we review the
      available data on G domain structure, together with a detailed analysis of the
      mechanism of action. We also present small G protein regulators: GTPase
      activating proteins that bind to a catalytic G domain and increase its low
      intrinsic hydrolase activity, GTPase dissociation inhibitors that stabilize the
      GDP-bound, inactive state of G proteins, and guanine nucleotide exchange factors
      that accelerate nucleotide exchange in response to cellular signals.
      Additionally, in this paper we describe some aspects of small G protein
      interactions with down-stream effectors.

PMID- 11995996
TI  - GTP-binding properties of the membrane-bound form of porcine liver annexin VI.
AB  - Annexin VI (AnxVI) of molecular mass 68-70 kDa belongs to a multigenic family of
      ubiquitous Ca2+- and phospholipid-binding proteins. In this report, we describe
      the GTP-binding properties of porcine liver AnxVI, determined with a fluorescent
      GTP analogue, 2'-(or 3')-O-(2,4,6-trinitrophenyl)guanosine 5'-triphosphate (TNP
      GTP). The optimal binding of TNP-GTP to AnxVI was observed in the presence of
      Ca2+ and asolectin liposomes, as evidenced by a 5.5-fold increase of TNP-GTP
      fluorescence and a concomitant blue shift (by 17 nm) of its maximal emission
      wavelength. Titration of AnxVI with TNP-GTP resulted in the determination of the
      dissociation constant (Kd) and binding stoichiometry that amounted to 1.3 microM
      and 1:1 TNP-GTP/AnxVI, mole/mole, respectively. In addition, the intrinsic
      fluorescence of the membrane-bound form of AnxVI was quenched by TNP-GTP and this
      was accompanied by fluorescence resonance energy transfer (FRET) from AnxVI Trp
      residues to TNP-GTP. This indicates that the GTP-binding site within the AnxVI
      molecule is probably located in the vicinity of a Trp-containing domain of the
      protein. By controlled proteolysis of human recombinant AnxVI, followed by
      purification of the proteolytic fragments by affinity chromatography on GTP
      agarose, we isolated a 35 kDa fragment corresponding to the N-terminal half of
      AnxVI containing Trp192. On the basis of these results, we suggest that AnxVI is
      a GTP-binding protein and the binding of the nucleotide may have a regulatory
      impact on the interaction of annexin with membranes, e.g. formation of ion
      channels by the protein.

PMID- 11995997
TI  - Structural basis of negative cooperativity in transthyretin.
AB  - A comparison of the AC and BD binding sites of transthyretin (TTR) was made in
      terms of the interatomic distances between the Ca atoms of equivalent amino
      acids, measured across the tetramer channel in each binding site. The comparison
      of the channel diameter for apo TTR from different sources revealed that in the
      unliganded transthyretin tetramers the distances between the A, D and H beta
      strands are consistently larger, while the distances between the G beta-strands
      are smaller in one site than in the other. These differences might be described
      to have a 'wave' character. An analogous analysis performed for transthyretin
      complexes reveals that the shape of the plot is similar, although the amplitudes
      of the changes are smaller. The analysis leads us to a model of the changes in
      the binding sites caused by ligand binding. The sequence of events includes
      ligand binding in the first site, followed by a slight collapse of this site and
      concomitant opening of the second site, binding of the second molecule and
      collapse of the second site. The following opening of the first, already occupied
      site upon ligand binding in the second site is smaller because of the bridging
      interactions already formed by the first ligand. This explains the negative
      cooperativity (NC) effect observed for many ligands in transthyretin.

PMID- 11995998
TI  - Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1 and
      1.8 A resolution.
AB  - The crystal structure of rat transthyretin (rTTR) complex with 3,5,3',5'
      tetraiodothyroacetic acid (T4Ac) was determined at 1.8 A resolution with low
      temperature synchrotron data collected at CHESS. The structure was refined to R =
      0.207 and Rfree = 0.24 with the use of 8-1.8 A data. The additional 8000
      reflections from the incomplete 2.1-1.8 data shell, included in the refinement,
      reduced the Rfree index by 1.3%. Structure comparison with the model refined
      against the complete 8-2.1 A data revealed no differences in the ligand
      orientation and the conformation of the polypeptide chain in the core regions.
      However, the high-resolution data included in the refinement improved the model
      in the flexible regions poorly defined with the lower resolution data. Also
      additional sixteen water molecules were found in the difference map calculated
      with the extended data. The structure revealed both forward and reverse binding
      of tetraiodothyroacetic acid in one binding site and two modes of forward ligand
      binding in the second site, with the phenolic iodine atoms occupying different
      sets of the halogen binding pockets.

PMID- 11995999
TI  - Comparison of binding interactions of dibromoflavonoids with transthyretin.
AB  - The crystal structure of rat transthyretin (rTTR) complex with the dibromoflavone
      EMD21388 was determined to 2.3 A resolution and refined to R = 0.203 and Rfree =
      0.288. Two different orientations of EMD21388, which differ in the channel
      penetration by 1.6 A, were found in the A/C binding site of rTTR. The single
      ligand position observed in the BID site is intermediate between the two
      positions found in the A/C site. The position of the dibromoflavone in the B/D
      site is similar to that reported for dibromoaurone in human TTR. The bromine
      atoms of EMD21388 form strong interactions in the P3 and P3' pockets of rTTR. Due
      to the different molecular architectures of both ligands, dibromoflavone forms
      only one interaction with Lys-15 near the channel entrance, while direct
      interactions with the pair of Lys-15 were reported for dibromoaurone. The C3*
      methyl group of EMD21388 mediates the bridging interactions between two TTR
      subunits in the P2 pockets. The interactions of the O2* hydroxyl group of
      dibromoaurone with the Thr-119 side chain in the P3 pockets are not matched by
      similar interactions in EMD21388. Both these alternative interactions can explain
      the competitive binding of 3',5'-dibromoflavonoids to transthyretin.

PMID- 11996000
TI  - Sequence analysis of enzymes with asparaginase activity.
AB  - Asparaginases catalyze the hydrolysis of asparagine to aspartic acid and ammonia.
      Enzymes with asparaginase activity play an important role both in the metabolism
      of all living organisms as well as in pharmacology. The main goal of this paper
      is to attempt a classification of all known enzymes with asparaginase activity,
      based on their amino acid sequences. Some possible phylogenetic consequences are
      also discussed using dendrograms and structural information derived from
      crystallographic studies.

PMID- 11996001
TI  - Computer modeling studies of the structural role of NADPH binding to active site
      mutants of human dihydrofolate reductase in complex with piritrexim.
AB  - Dihydrofolate reductase (DHFR, EC 1.5.1.3) is one of the enzymes active in the
      folate cycle which plays an important role in DNA synthesis. Inhibition of DHFR
      is a key element in the treatment of many diseases, including cancer and AIDS
      related infections. A search for new selective inhibitors is motivated by the
      resistance to common drugs observed in the course of treatment. In this paper,
      results of a detailed computer analysis of human DHFR interactions with the
      lipophilic inhibitor piritrexim (PTX) are presented. It was found that the NADPH
      cofactor contributes 30% of the total PTX-enzyme interaction energy. Substitution
      of the highly conserved Glu30 with alanine does not lead to the release of the
      inhibitor from the hDHFR pocket. The important L22F point mutation does affect
      PTX orientation but does not changethe binding energy. Simulations of the
      dynamics of binary hDHFR-PTX complexes were performed with the use of Extensible
      Systematic Force Field (ESFF) and the results indicate structural changes in the
      enzyme induced by NADPH binding.

PMID- 11996002
TI  - Two disulphide bridges are present in juvenile hormone binding protein from
      Galleria mellonella.
AB  - The hemolymph juvenile hormone binding protein (JHBP) from Galleria mellonella
      contains two disulphide bridges/molecule and no free Cys residues. An alignment
      of primary structures of other Lepidopteran JHBPs indicates that Cys residues,
      equivalent to Cys10,17,151,195 in G. mellonella JHBP, maybe involved in -S-S-
      bridge formation.

PMID- 11996003
TI  - Protein phosphatase 2A: variety of forms and diversity of functions.
AB  - Protein phosphatase 2A (PP2A) comprises a diverse family of phosphoserine- and
      phosphothreonine-specific phosphatases present in all eukaryotic cells. All forms
      of PP2A contain a catalytic subunit (PP2Ac) which forms a stable complex with the
      structural subunit PR65/A. The heterodimer PP2Ac-PR65/A associates with
      regulatory proteins, termed variable subunits, in order to form trimeric
      holoenzymes attributed with distinct substrate specificity and targeted to
      different subcellular compartments. PP2Ac activity can be modulated by reversible
      phosphorylation on Tyr307 and methylation on C-terminal Leu309. Studies on PP2A
      have shown that this enzyme may be implicated in the regulation of metabolism,
      transcription, RNA splicing, translation, differentiation, cell cycle, oncogenic
      transformation and signal transduction.

PMID- 11996004
TI  - Understanding the evolution of restriction-modification systems: clues from
      sequence and structure comparisons.
AB  - Restriction-modification (RM) systems comprise two opposing enzymatic activities:
      a restriction endonuclease, that targets specific DNA sequences and performs
      endonucleolytic cleavage, and a modification methyltransferase that renders these
      sequences resistant to cleavage. Studies on molecular genetics and biochemistry
      of RM systems have been carried out over the past four decades, laying
      foundations for modern molecular biology and providing important models for
      mechanisms of highly specific protein-DNA interactions. Although the number of
      known, relevant sequences 3D structures of RM proteins is growing steadily, we do
      not fully understand their functional diversities from an evolutionary
      perspective and we are not yet able to engineer new sequence specificities based
      on rational approaches. Recent findings on the evolution of RM systems and on
      their structures and mechanisms of action have led to a picture in which
      conserved modules with defined function are shared between different RM proteins
      and other enzymes involved in nucleic acid biochemistry. On the other hand, it
      has been realized that some of the modules have been replaced in the evolution by
      unrelated domains exerting similar function. The aim of this review is to give a
      survey on the recent progress in the field of structural phylogeny of RM enzymes
      with special emphasis on studies of sequence-structure-function relationships and
      emerging potential applications in biotechnology.

PMID- 11996005
TI  - Cloning of the Haemophilus influenzae Dam methyltransferase and analysis of its
      relationship to the Dam methyltransferase encoded by the HP1 phage.
AB  - In this paper we report cloning and experimental characterization of the DNA
      adenine methyltransferase (dam) gene from Haemophilus influenzae and comparison
      of its product with the Dam protein from the lysogenic phage of H. influenzae,
      HP1. Molecular modeling of M.HinDam and M.HP1Dam was carried out, providing a
      framework for a comparative analysis of these enzymes and their close homologs in
      the structural context. Both proteins share the common fold and essential
      cofactor-binding and catalytic residues despite overall divergence. However,
      subtle but significant differences in the cofactor-binding pocket have been
      identified. Moreover, while M.HinDam seems to contact its target DNA sequence
      using a number of loops, most of them are missing from M.HP1Dam. Analysis of both
      MTases suggests that their catalytic activity was derived from a common ancestor,
      but similar sequence specificities arose by convergence.

PMID- 11996006
TI  - Mg2+ does not induce isomerization of the open transcription complex of
      Escherichia coli RNA polymerase at the model Pa promoter bearing consensus -10
      and -35 hexamers.
AB  - The kinetics and thermodynamics of the formation of the transcriptional open
      complex (RPo) by Escherichia coli RNA polymerase at the synthetic Pa promoter
      bearing consensus -10 and -35 recognition hexamers were studied in vitro.
      Previously, this promoter was used as a control one in studies on the effect of
      DNA bending by An x Tn sequences on transcription initiation and shown to be
      fully functional in E. coli (Lozinski et al., 1991, Nucleic Acids Res. 19, 2947;
      Lozinski & Wierzchowski, 1996, Acta Biochim. Polon. 43, 265). The data now
      obtained demonstrate that the mechanism of Pa-RPo formation and dissociation
      conforms to the three-step reaction model: bind-nucleate-melt, commonly accepted
      for natural promoters. Measurements of the dissociation rate constant of Pa-RPo
      as a function of MgCl2 concentration allowed us to determine the number of Mg2+
      ions, nMg approximately/= 4, being bound to the RPo in the course of renaturation
      of the melted DNA region. This number was found constant in the temperature range
      of 25-37 degrees C, which indicates that under these conditions the complex
      remaines fully open. This observation, taken together with the recent evidence
      from KMnO4 footprinting studies that the length of the melted region in Pa-RPo at
      37 degrees C is independent of the presence of Mg2+ ions (Lozinski &
      Wierzchowski, 2001, Acta Biochim. Polon. 48, 495), testifies that binding of Mg2+
      to RPo does not induce its further isomerization, which has been postulated for
      the lambdaP(R)-RPo complex (Suh et al., 1992, Biochemistry 31, 7815; 1993,
      Science 259, 358).

PMID- 11996007
TI  - Influence of Me2SO and incubation time on papain activity studied using
      fluorogenic substrates.
AB  - Papain activity in a buffer containing Me2SO was studied using fluorogenic
      substrates. It was found that the number of active sites of papain decreases with
      increasing Me2SO concentration whereas the incubation time, in a buffer
      containing 3% Me2SO does not affect the number of active sites. However, an
      increase of papain incubation time in the buffer with 3% Me2SO decreased the
      initial rate of hydrolysis of Z-Phe-Arg-Amc as well as Dabcyl-Lys-Phe-Gly-Gly-Ala
      Ala-Edans. Moreover, an increase of Me2SO concentration in working buffer
      decreased the initial rate of papain-catalysed hydrolysis of both substrates. A
      rapid decrease of the initial rate (by up to 30%) was observed between 1 and 2%
      Me2SO. Application of the Michaelis-Menten equation revealed that at the higher
      Me2SO concentrations the apparent values of k(cat)/Km decreased as a result of Km
      increase and kcat decrease. However, Me2SO changed the substrate binding process
      more effectively (Km) than the rate of catalysis k(cat).

PMID- 11996008
TI  - Introductory remarks on human CYPs.

PMID- 11996009
TI  - Characteristics and common properties of inhibitors, inducers, and activators of
      CYP enzymes.

PMID- 11996010
TI  - Human CYPs: in vivo and clinical aspects.

PMID- 11996011
TI  - Drugs as P-glycoprotein substrates, inhibitors, and inducers.

PMID- 11996012
TI  - Molecular modeling of human cytochrome P450-substrate interactions.
AB  - The results of homology modeling of 10 human cytochrome P450 (CYP) enzymes
      involved in the Phase 1 metabolism of drugs and other foreign compounds are
      reported. The models have been constructed from the CYP102 hemoprotein domain
      template for which the substrate-bound crystallographic coordinates are
      available. Selective substrates of individual human P450s: CYP1A2, CYP2A6,
      CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11 are all
      shown to fit within the corresponding enzymes' active sites in such a manner that
      is consistent with reported experimental data for both known pathways of
      substrate metabolism and from the results of site-directed mutagenesis, either in
      those particular human P450 enzymes concerned or for ones within the same
      subfamily. The self-consistency of these homology models indicates that they may
      have potential utility for the pre-screening of novel drug structures.

PMID- 11996013
TI  - Structure-activity relationship for human cytochrome P450 substrates and
      inhibitors.
AB  - Criteria governing the avidity of substrate binding to human hepatic cytochromes
      P450 (CYP) associated with Phase 1 metabolism of drugs are described. The results
      of extensive quantitative structure-activity relationship (QSAR) analyses are
      reported for substrates of human P450s: CYPIA2, CYP2A6, CYP2B6, CYP2C9, CYP2C19,
      CYP2D6, CYP2E1, and CYP3A4, representing the enzymes exhibiting major involvement
      in the metabolism of drug substrates in Homo sapiens. In particular, it is shown
      that hydrogen bond properties in each class of enzyme-substrate complex are
      especially important factors in determining substrate binding affinity towards
      those human P450s which are involved in drug metabolism.

PMID- 11996014
TI  - Update information on human P450s.

PMID- 11996015
TI  - Summary of information on human CYP enzymes: human P450 metabolism data.
AB  - This chapter is an update of the data on substrates, reactions, inducers, and
      inhibitors of human CYP enzymes published previously by Rendic and DiCarlo (1),
      now covering selection of the literature through 2001 in the reference section.
      The data are presented in a tabular form (Table 1) to provide a framework for
      predicting and interpreting the new P450 metabolic data. The data are formatted
      in an Excel format as most suitable for off-line searching and management of the
      Web-database. The data are presented as stated by the author(s) and in the case
      when several references are cited the data are presented according to the latest
      published information. The searchable database is available either as an Excel
      file (for information contact the author), or as a Web-searchable database (Human
      P450 Metabolism Database, www.gentest.com) enabling the readers easy and quick
      approach to the latest updates on human CYP metabolic reactions.

PMID- 11996016
TI  - Respirator performance terminology.

PMID- 11996017
TI  - Potential interferences in carbon monoxide sensor performance from ethyl alcohol.

PMID- 11996018
TI  - PAT Program report: background and current status. Proficiency Analytical
      Testing.

PMID- 11996019
TI  - ELPAT Program report: background and current status. Environmental Lead
      Proficiency Analytical Testing.

PMID- 11996020
TI  - Social capital and health (plus wealth, income inequality and regional health
      governance).
AB  - This article describes an empirical exploration of relationships among aspects of
      thirty health districts in Saskatchewan, Canada. These aspects include social
      capital, income inequality, wealth, governance by regional health authorities and
      population health, the primary dependent variable. The social capital index
      incorporated associational and civic participation, average and median household
      incomes served as proxies for wealth, the degree of skew in the distribution of
      household incomes assessed income inequality while the model for effective
      governance by District Health Boards (DHBs) focused on reflection of health
      needs, policy making and implementation, fiscal responsibility and the
      integration and co-ordination of services. I found no evidence of a relationship
      between social capital in health districts and the performance of DHBs. Among the
      determinants of health, wealth appeared unrelated to age-standardised mortality
      rates while income inequality was positively and social capital was negatively
      related to mortality. Income inequality was not as strongly related to age
      standardised mortality after controlling for social capital. and vice versa,
      suggesting the two may be comingled somehow when it comes to population health,
      although they were not significantly related to one another. Of the predictors of
      social capital the distribution of age in districts appeared to be the most
      salient; of the predictors of age-standardised mortality rates the gender
      composition of a district was most salient.

PMID- 11996021
TI  - Private medical practitioners and managed care in Malaysia: a survey of knowledge
      and attitudes held by Federal Territory based doctors.
AB  - This paper considers the subject of managed care in Malaysia, providing a
      questionnaire-based analysis of the position adopted by private medical
      practitioners. Managed care is now seen as the dominant health care system in the
      United States, with many other countries around the world including Malaysia
      beginning to selectively use component parts to tackle particular health care
      problems. In this survey it was found that three out of four respondents have
      concerns regarding the implementation of managed care. The survey was used to
      identify and categorise these concerns. At the same time, three out of four
      respondents held the opinion that principles of managed care were already a
      reality or would be in the next 5 years. This group expressed an eagerness to be
      trained in managed care principles and be given the opportunity to be part of
      managed care organisations. It is argued that clinicians' knowledge and interest
      perceptions are an important influence on the implementation of managed care
      based systems. The survey-based evidence presented in this article is intended as
      a measure of current understandings and beliefs, in relation to clinical micro
      management process associated with managed care.

PMID- 11996022
TI  - Managed care members talk about trust.
AB  - Informed choice of health insurance could morally justify later, potentially
      harmful rationing decisions the way informed consent justifies potentially
      harmful medical interventions. In complex and technical areas, however,
      individuals may base decisions more on trust than informed choice. We interviewed
      enrollees in managed care plans in Southeast Michigan, United States, to explore
      in detail their expectations and experiences in choosing and using their health
      plan. Diverse subjects participated in semi-structured interviews about health
      insurance choices, experiences, and expectations. Results are presented for the
      theme of trust (and distrust), which emerged spontaneously in discussions about
      health care and health insurance. Forty subjects diverse in age, ethnicity, and
      income took part in 31 interviews. Interviewees mentioned many of the elements of
      interpersonal trust in specific physicians, often in the context of discussions
      about care experiences, doctor payment, and conflict of interest. Elements
      included physical and emotional vulnerability, expectations of goodwill, advocacy
      and competence. and belief in professional ethics. Trust in the medical
      profession had more hesitancy, and often included mention of honesty or ethics.
      Elements of trust in hospitals included vulnerability to financial loss, and
      expectations of competence (quality). Elements of trust in health insurance plans
      often emerged in discussions about catastrophic illness coverage denials, and
      profit, and were more often negative. Vulnerability, worry, fear and security
      were prominent. Fiscal rather than clinical competence was emphasized, while
      expectations of goodwill remained. Enrollees in managed care plans spontaneously
      discussed trust and distrust in individuals and institutions during conversations
      about their insurance expectations and experiences. Similarities and differences
      in the elements and the context of these discussions illuminate distinctions
      between these healthcare relationships of trust.

PMID- 11996023
TI  - The theory of use behind telemedicine: how compatible with physicians' clinical
      routines?
AB  - Since the early 1990s, telemedicine, or the use of information technology to
      support the delivery of health care from a distance, has increasingly gained the
      support of clinicians, administrators and policymakers across industrialised
      countries. However, the "theory of use" behind telemedicine-its rationale and the
      manner in which clinicians are expected to use it in their daily activities--has
      been only marginally investigated. In this paper we present the results of a
      qualitative study which examines the theory of use behind teleconsultation from
      the viewpoint of physicians (n = 37) in six specialities, practising in Quebec
      (Canada) hospitals. We employ Giddens' Structuration Theory (1984) to analyse the
      views, communications needs and referral strategies of physicians. Two questions
      are explored: (1) To what extent can teleconsultation be integrated into the
      routines of diverse medical specialities'? and (2) Why and how might clinicians
      use this technology? Our research indicates that specialities relying on either
      thorough physical examinations or specialised investigative techniques are
      unlikely to restructure their work routines to accommodate teleconsultation,
      which they view as limited. Specialities that primarily exploit images or
      numerical data tend to perceive teleconsultation as more useful. The perceived
      enabling properties of teleconsultation increase as a function of the distance
      the patient would have to travel to be seen directly by a consultant. The
      constraining properties are linked to the type of information transmitted, since
      physicians believe that only objective data can be safely consulted from a
      distance, whereas relying on the remote physician's interpretation of subjective
      information is deemed inappropriate. We thus conclude that the development of
      teleconsultation should be consolidated around applications whose theory of use
      is compatible with existing clinical routines, or offers opportunities to
      restructure clinical work according to the needs of providers and remote
      communities.

PMID- 11996024
TI  - The influence of user fees and patient demand on prescribers in rural Nepal.
AB  - Irrational prescribing and over-prescription is a world-wide problem. Prescribers
      often cite patient demand as one of the main reasons why they over-prescribe, but
      the degree to which this is so is unknown. This article describes a study to test
      the hypothesis that patient demand causes over-prescription. The study occurred
      within the context of different kinds of nominal user fee for drugs in Nepal,
      where it was assumed that charging per drug item would deter patient demand, and
      hence over-prescription, as compared to charging per prescription. Focus group
      discussions with patients attending rural health facilities explored patient
      attitudes towards drugs. Patients and health workers were interviewed to gather
      quantitative data on (1) patient demand, and (2) health worker views of patient
      demand and their own prescribing habits, and comparing these with the drugs
      actually prescribed and dispensed to patients. Patients felt they needed more
      drugs than they were prescribed or dispensed, but stated that they would be happy
      to accept advice from prescribers for fewer drugs. In all areas of whatever fee
      type, there was no association between the number of drug items patients felt
      they needed pre-consultation and the number of drug items that they actually
      received as observed postconsultation. However, there was a significant
      association between the average number of drug items per patient that prescribers
      stated they usually prescribed and the actual number that were prescribed. It was
      concluded that patient demand was not affected by different kinds of user fee and
      did not directly influence prescribing behaviour.

PMID- 11996025
TI  - To what extent can we explain time trade-off values from other information about
      respondents?
AB  - The time trade-off (TTO) is one of the most widely used health state valuation
      methods and was recently used to develop a set of values for the EQ-5D
      descriptive system from 3000 members of the UK general population. However, there
      is currently very little understanding of precisely what determines responses to
      TTO questions. The data that were used to generate this set of values are ideal
      for addressing this question since they contain a plethora of information
      relating to the respondents and their cognition during the TTO exercise. A
      particularly useful characteristic of this dataset is the existence of visual
      analogue scale (VAS) valuations on the same states for the same respondents. The
      results suggest that age, sex and marital status are the most important
      respondent characteristics determining health state valuations. The VAS
      valuations were found to add very little to the explanatory power of the models.

PMID- 11996026
TI  - Predicting small area health-related behaviour: a comparison of multilevel
      synthetic estimation and local survey data.
AB  - A recent paper in Social Science and Medicine (Twigg et al. 50 (2000) 1109)
      outlined an approach to the estimation of prevalences of small-area health
      related behaviour using multilevel models. This paper compares results from the
      application of the multilevel approach with those derived using the more
      traditional strategy of the local 'lifestyle' survey. Estimations of smoking
      prevalence and high alcohol consumption are examined and critical assessments
      made of both estimation approaches. It is concluded that the alternative method
      is more suited towards the prediction of smoking rates as opposed to unsafe
      alcohol consumption.

PMID- 11996027
TI  - Market reforms and public incentives: finding a balance in the Republic of
      Macedonia.
AB  - The Republic of Macedonia is undertaking sweeping reforms of its health sector.
      Funded by a World Bank credit, the reforms seek to improve the efficiency and
      quality of primary health care (PHC) by significantly strengthening the role of
      the market in health care provision. On the supply-side, one of the key reform
      proposals is to implement a capitation payment system for PHC physicians. By
      placing individual physicians on productivity-based contracts, these reforms will
      effectively marketize all PHC provision. In addition, the Ministry of Health is
      considering the sale or concessions of public PHC clinics to private groups,
      indicating the government's commitment to marketization of health care provision.
      Macedonia is in a unique position to develop a new role for the private sector in
      PHC provision. The private provision of outpatient care was legalized soon after
      independence in 1991; private physicians now account for nearly 10% of all
      physicians and 22% of PHC physicians. If the reforms are fully realized, all PHC
      physicians-over 40% of all physicians-will be financially responsible for their
      clinical practices. This study draws on Macedonia's experience with limited
      development of private outpatient care starting in 1991 and the reform proposals
      for PHC, finding a network of policies and procedures throughout the health
      sector that negatively impact private and public sector provision. An assessment
      of the effects that this greater policy environment has on private sector
      provision identifies opportunities to strategically enhance the reforms. With
      respect to established market economies, the study finds justification for a
      greater role for government intervention in private health markets in transition
      economies. In addition to micro-level payment incentives and administrative
      controls, marketization in Central and Eastern Europe requires an examination of
      insurance contracting procedures, quality assurance practices, public clinic
      ownership, referral practices, hospital privileges, and capital investment
      policies.

PMID- 11996028
TI  - Representations of far-flung illnesses: the case of Ebola in Britain.
AB  - In western cultures lay people are faced with a plethora of far-flung illnesses,
      relayed to them by the mass media. A number of social scientists have called for
      scrutiny of the link between people's patterns of thinking concerning such
      events, and the messages to which they are exposed. Using the outbreaks of Ebola
      in Africa in the mid-1990s as a vehicle, the study examines how British
      broadsheets and their readers, and British tabloids and their readers, make sense
      of this far-flung illness. Existing work on early representations of HIV/AIDS in
      the west is utilised to inform the research questions. In particular, this study
      investigates whether Ebola is constructed as a threat, how media and lay
      representations of Ebola interact, and whether there are different pockets of
      shared thinking, or a more uniform representation, in relation to Ebola in
      Britain. An analysis of the themes in 48 broadsheet and tabloid articles, and 50
      interviews with their readers, reveals a common picture in which Ebola is
      represented as African. associated with African practices, and seen as posing
      little threat to Britain. However, group differences exist, and are characterised
      by a more essentialised vision of Ebola in the tabloids and their readers, in
      contrast to a focus on structural features linked to Ebola's escalation in the
      broadsheets and their readers. In terms of the media-mind relationship, beyond
      the similarities found between media type and their respective readers' ideas,
      certain key differences exist: While the newspapers make Ebola 'real' by
      referring to its potential to globalise. as well as to how it can be contained,
      lay thinkers feel detached from it, and draw an analogy between Ebola and science
      fiction. This is discussed as a method of symbolic coping on the part of the
      readers, as well as in terms of the power exerted by media imagery on lay
      representations of Ebola.

PMID- 11996029
TI  - Body image and physical disability--personal perspectives.
AB  - The current study used qualitative methodology to investigate the body image
      concerns of people with physical disabilities. Three males and four females aged
      between 22 and 50 years, in Melbourne, Australia, participated in the study.
      Three participants were heterosexual, two were homosexual and two described their
      sexual identity as predominantly heterosexual but 'bicurious'. The data were
      gathered through individual interviews of approximately 2 h duration, where
      participants responded to a set of predetermined open-ended questions. The study
      found that bodily impairment had a negative influence on the participants'
      psychological experiences, feelings and attitudes toward their own bodies. The
      impact of feedback from the social environment was highlighted, and there was
      evidence suggesting that individuals gradually adjust to their different bodies
      and increasingly accept their disabilities over time.

PMID- 11996030
TI  - The impact of hospices on health care expenditures--the case of Taiwan.
AB  - Cancer has been the leading cause of death in Taiwan since 1982, with nearly one
      out of four deaths caused by malignant neoplasm. The huge amount of money being
      spent in the acute care setting for terminally ill cancer patients does not
      increase their wellbeing. In this study, we employ an Instrumental Variable (IV)
      model to correct for the self-selection problem and use population-based
      insurance claim data to test two null hypotheses: there is no difference in total
      expenditures between hospice care and conventional care, and that there is no
      difference in total expenditures between hospital-based hospice care and home
      hospice care. Both null hypotheses are rejected.

PMID- 11996031
TI  - Miniature specimen shear punch test for UHMWPE used in total joint replacements.
AB  - Despite the critical role that shear is hypothesized to play in the damage modes
      that limit the performance of total hip and knee replacements, the shear behavior
      of ultra-high molecular weight polyethylene (UHMWPE) remains poorly understood,
      especially after oxidative degradation or radiation crosslinking. In the present
      study, we developed the miniature specimen (0.5 mm thickness x 6.4mm diameter)
      shear punch test to evaluate the shear behavior of UHMWPE used in total joint
      replacement components. We investigated the shear punch behavior of virgin and
      crosslinked stock materials, as well as of UHMWPE from tibial implants that were
      gamma-irradiated in air and shelf aged for up to 8.5 years. Finite element
      analysis, scanning electron microscopy, and interrupted testing were conducted to
      aid in the interpretation of the shear punch load-displacement curves. The shear
      punch load-displacement curves exhibited similar distinctive features. Following
      toe-in, the load-displacement curves were typically bilinear, and characterized
      by an initial stiffness, a transition load, a hardening stiffness, and a peak
      load. The finite element analysis established that the initial stiffness was
      proportional to the elastic modulus of the UHMWPE, and the transition load of the
      bilinear curve reflected the development of a plastically deforming zone
      traversing through the thickness of the sample. Based on our observations, we
      propose two interpretations of the peak load during the shear punch test: one
      theory is based on the initiation of crystalline plasticity, the other based on
      the transition from shear to tension during the tests. Due to the miniature
      specimen size, the shear punch test offers several potential advantages over bulk
      test methods, including the capability to directly measure shear behavior, and
      quite possibly infer ultimate uniaxial behavior as well, from shelf aged and
      retrieved UHMWPE components. Thus, the shear punch test represents an effective
      and complementary new tool in the armamentarium of miniature specimen mechanical
      testing methods for UHMWPE used in total joint replacement components.

PMID- 11996032
TI  - Influence of ionic strength and carbonate on the Ca-P coating formation from
      SBFx5 solution.
AB  - Biomimetic calcium-phosphate (Ca-P) coatings were applied on Ti6Al4V by using
      simulated body fluids concentrated by a factor 5 (SBFx5). The production of SBFx5
      solution was possible by decreasing the pH of the solution to approximately 6
      using CO2 gas. The subsequent release of this mildly acidic gas led to a pH rise
      and thus, increasing supersaturation. After immersion for 5(1/2) h a Ca-P coating
      on Ti6Al4V plates and a precipitate simultaneously formed at pH = 6.8. Sodium
      chloride (NaCl) and hydrogencarbonate (HCO3) contents were studied in relation to
      CO2 release and coating formation by changing their individual concentration in
      SBFx5 solution. On one hand, NaCl-free or low NaCl-content SBFx5 solution led to
      the earlier aspecific precipitation in the solution than for SBFx5 solution. In
      contrast, Ca-P coating was formed later and was thinner than the coating obtained
      in regular SBFx5 solution. High ionic strength delayed precipitation and favored
      Ca-P heterogeneous nucleation on Ti6Al4V. On the other hand, HCO3- content
      increased the pH of the solution due to its buffering capacity and influenced the
      release rate of dissolved CO2. Thus, HCO3- content strongly affected the
      supersaturation and Ca-P structure. Furthermore, HCO3- favored the attachment of
      Ca-P mineral on Ti6Al4V by decreasing Ca-P crystal size resulting in a better
      physical attachment of Ca-P coating on Ti6Al4V substrate.

PMID- 11996033
TI  - Initial tissue response to a titanium implant coated with apatite at room
      temperature using a blast coating method.
AB  - We previously reported a blast coating method (BC method) as a new coating method
      of titanium (Ti) with apatite (AP) at room temperature. The BC method gives much
      stronger AP coating on the Ti surface compared with those obtained by other room
      temperature coating methods. However, no in vivo study has been made, so far, to
      evaluate the stability or the tissue response to the implant. As an initial step
      to evaluate the feasibility of the BC method, we evaluated the tissue response
      and stability of AP coated Ti implant prepared with the BC method (AP-BC implant)
      using rats as experimental animals. The AP coating adhered tightly to the Ti
      surface even after the implant procedure and throughout the experimental period
      up to six weeks post operation. AP-BC implant caused no inflammatory response,
      showed strong bone response and much better osteoconductivity compared with the
      pure Ti implant. The new bone formed on the surface of AP-BC implants was thinner
      compared with that formed on the surface of Ti implant. Therefore, the AP-BC
      implant has a good potential as an osteoconductive implant material.

PMID- 11996034
TI  - Hydroxyapatite-coated Ti-6Al-4V part 1: the effect of coating thickness on
      mechanical fatigue behaviour.
AB  - The present investigation examines the effect of coating thickness on the fatigue
      behaviour of hydroxyapatite (HA)-coated Ti-6Al-4V. Uniaxial fatigue tests were
      conducted on grit blasted Ti-6Al-4V coupons with HA coatings deposited by
      atmospheric plasma-spray at thicknesses of 0, 25, 50, 75, 100, and 150 microm, as
      well as on grit blasted specimens that had received a stress relieving heat
      treatment. Coupons with 150 microm HA coatings were shown to have significantly
      decreased fatigue resistances, with lives similar to those of the stress relieved
      specimens, while coatings of thickness 25-100 microm were found to have no affect
      on fatigue resistance. Residual stresses generated during deposition, cracks
      propagating towards the substrate from within the coating, and stress relief due
      to heat inputs from the spraying process were all considered with respect to
      their potential effects on fatigue behaviour. Stress relief in the substrate due
      to enhanced heat transfer mechanisms was identified as the most likely source of
      the observed reductions in substrate fatigue life in the 150 microm coupons.

PMID- 11996035
TI  - Hydroxyapatite-coated Ti-6Al-4V part 2: the effects of post-deposition heat
      treatment at low temperatures.
AB  - The present investigation explores the effects of a 90-h post-deposition
      annealing treatment at 400 degrees C in air on the crystallographic and chemical
      properties of a plasma-sprayed hydroxyapatite (HA) coating, the thickness and
      composition of the interfacial oxide layer, and the fatigue behaviour of the
      underlying Ti-6Al-4V substrate. X-ray diffraction analysis revealed that
      significant recovery of the crystalline HA structure occurred as a result of the
      treatment, however, as compared with results obtained through treatment at higher
      temperatures, recovery obtained through use of the present treatment was
      incomplete. X-ray photoelectron spectroscopy analysis showed no changes in the
      constituents of the oxide layer, with the oxide species TiO2, Al2O3, V2O5, V2O3,
      and VO2 present on both the as-sprayed and the heat-treated substrates. A change
      in film thickness was observed, however, as evidenced by a change in colour from
      opaque bronze to dark purple. The fatigue resistance of the substrate was found
      to be significantly reduced by the heat treatment, with the lives of heat-treated
      coupons with coatings of all thicknesses closely resembling those of as-sprayed
      coupons with thick HA coatings and uncoated stress-relieved coupons presented in
      Part I of this study. Stress relief was identified as the most likely cause of
      these reductions.

PMID- 11996036
TI  - Starch-based biodegradable hydrogels with potential biomedical applications as
      drug delivery systems.
AB  - The design and preparation of novel biodegradable hydrogels developed by the free
      radical polymerization of acrylamide and acrylic acid, and some formulations with
      bis-acrylamide, in the presence of a corn starch/ethylene-co-vinyl alcohol
      copolymer blend (SEVA-C), is reported. The redox system benzoyl peroxide (BPO)
      and 4-dimethylaminobenzyl alcohol (DMOH) initiated the polymerization at room
      temperature. Xerogels were characterized by 1H NMR and FTIR spectroscopies.
      Swelling studies were performed as a function of pH in different buffer solutions
      determining the water-transport mechanism that governs the swelling behaviour.
      Degradation studies of the hydrogels were performed in simulated physiological
      solutions for time up to 90 days, determining the respective weight loss, and
      analyzing the solution residue by 1H NMR. The mechanical properties of the
      xerogels were characterized by tensile and compressive tests, as well as by
      dynamo-mechanical analysis (DMA). Dynamo-mechanical parameters are also reported
      for hydrated samples.

PMID- 11996037
TI  - Platelet adhesion to commercial and modified polymer materials in animals under
      psychological stress and in a no-stress condition.
AB  - It is well known that stressful stimuli change blood functions and that protein
      and platelet parameters are altered in humans and animals subjected to stress. We
      have examined the influence of psychological stress on the morphological
      responses of platelets on commercially available materials [polyester (VP),
      fluoropassivated polyester (VPF), non-woven benzylic ester of hyaluronic acid
      (Hyaff11)] and on materials synthesised (PUPA) and/or surface modified by
      sulphation (Hyaff11S) or by immobilisation of the anticoagulant molecules heparin
      and sulphated hyaluronic acid (PUPA-Heparin, PUPA-HyalS, HyalS-PET). Moreover,
      the anticoagulant activity (i.e. thrombin inactivation) of the materials was
      analysed. In the no-stress condition, the surfaces with a low degree of platelet
      adhesion were Hyaff11S, HyalS-PET, PUPA-Heparin and PUPA-HyalS. Hyaff11, PET and
      PUPA had the highest number of adherent platelets within the series. VP and VPF
      exhibited an intermediate behaviour. The exposure of animals to stress induced a
      dramatic change in platelet number and morphology on PET, HyalS-PET, PUPA, PUPA
      HyalS and Hyaff11: there was a higher degree of platelet adhesion, increased
      platelet spreading and the appearance of pseudopodia. In VP, VPF, Hyaff11S and
      PUPA-Heparin, there were no changes in platelet adhesion in stress conditions
      with respect to the no-stress condition; the latter two materials, the only ones
      able to prolong thrombin time, had a very low number of adherent platelets.

PMID- 11996038
TI  - Effects of chitin/chitosan and their oligomers/monomers on migrations of
      fibroblasts and vascular endothelium.
AB  - Effects of chitin/chitosan and their oligomers/monomers on migrations of
      fibroblasts (3T6) and vascular endothelial cells (human umbilical vascular
      endothelial cell: HUVEC) were evaluated in vitro. In direct migratory assay using
      the blind well chamber method, migratory activity of 3T6 was seen to be reduced
      by chitin, chitosan and the chitosan monomer (GlcN). Migratory activity of HUVECs
      was enhanced by chitin, chitosan and the chitin monomer (GlcNAc), and was reduced
      by chitosan oligomers and GlcN. Supernatant of 3T6 preincubated with chitin or
      chitosan reduced migratory activity of 3T6 cells. Supernatant of HUVECs
      preincubated with chitosan also reduced migratory activity of HUVECs, but
      supernatant preincubated with chitin had no effect on them. In a proliferation
      (MTT reduction) assay, none of the samples affected proliferation of either type
      of cell.

PMID- 11996039
TI  - A study of purified montmorillonite intercalated with 5-fluorouracil as drug
      carrier.
AB  - Since its introduction over 40 years ago, 5-fluorouracil (5-FU) has remained the
      only effective chemotherapy option available for the treatment of colorectal
      cancer (CRC). However, this cytotoxic anticancer drug often causes severe side
      effects because it does not act selectively on the tumor. It has been reported
      that the 5-FU showed considerable toxicity when administered by intravenous
      injections or via alimentary tract. Although, many materials have been developed
      for carrying 5-FU, there has been no clinically acceptable carrier for 5-FU till
      now. Montmorillonite, one of the clay minerals, consists of hydrated aluminum
      silicates with fine grains and large spaces between the layers. Isomorphous
      substitution of cations is common. In the study, we attempt to intercalate 5-FU
      into interlayers of montmorillonite through ion exchange. Montmorillonite was
      purified from crude clays of bentonite in Tai-dong, Taiwan by filtration and
      sedimentation. Solutions of 5-FU with different concentrations were prepared by
      dissolving various amounts of 5-FU into 10 ml NaOH solution. Purified
      montmorillonite powder was soaked in 5-FU solution for a period of time with
      different pH values and temperatures. In this study, we try to intercalate 5-FU
      into interlayers of montmorillonite to find out optimum conditions, such as
      soaking time, temperature, pH value, initial 5-FU concentration, etc., to prepare
      composites of 5-FU and montmorillonite (5-FU/mont). UV, SDT, FTIR, XRD are used
      to characterize the 5-FU/mont composite. From the results. 5-FU was successfully
      intercalated into the interlayer of montmorillonite both by free surface
      absorption and OH replacement. The optimum condition for 5-FU/mont preparations
      is 1.185 wt% of 5-FU as initial concentration under a pH value of 11.6 at a
      temperature of 80 degrees C and a soaking time of 2 h. The total amount of 5-FU
      in montmorillonite is about 87.5 mg for each gram of montmorillonite, which can
      be proved by thermal gravimetric analysis. The composite of 5-FU/mont is expected
      to achieve in situ release for colorectal cancer therapy in future applications.

PMID- 11996040
TI  - Characterization of calcium phosphate coatings deposited by Nd:YAG laser ablation
      at 355 nm: influence of thickness.
AB  - Calcium phosphate coatings were deposited by pulsed laser ablation with a
      radiation of 355 nm from a Nd:YAG laser. All the coatings were obtained at the
      same conditions, but deposition was stopped after different number of pulses to
      get coatings with different thickness. The influence of thickness in the
      structural and mechanical properties of the coatings was investigated. Coatings
      structure was characterised by scanning electron microscopy, grazing incidence X
      ray diffractometry and Raman spectroscopy. The mechanical properties were
      evaluated by scratch test. The morphology of the coatings is dominated by the
      presence of droplets. The coatings are composed mainly of hydroxyapatite, alpha
      tricalcium phosphate and amorphous calcium phosphate. Thinner coatings withstand
      higher loads of failure in the scratch test.

PMID- 11996041
TI  - Influence of fluoride content and pH on the corrosion resistance of titanium and
      its alloys.
AB  - In the last decade, new titanium alloys have been developed in different areas of
      dentistry, such as TiAl6V4 and NiTi. Concurrently, treatments using fluoride
      supplementation, such as odontology fluoride containing gels, have also been
      widely used in odontology. The aim of this study was to compare the NiTi, NiTiCo
      and TiAl6V4 alloys with the titanium, regarding the corrosion resistance in
      Fusayama Meyer artificial saliva with different pH and fluoride contents. In the
      experimental methods, the corrosion potential was measured over time, then a
      linear sweep voltametric analysis measured the polarization resistances and
      corrosion currents. Our results have shown that TiAl6V4 alloys have a good
      corrosion resistance as good as that of titanium in Fusayama Meyer saliva and
      acid salivary solution, except NiTi and NiTiCo alloys. Conversely, we noticed, as
      for the titanium, a remarkable localized corrosion phenomenon of those new alloys
      in fluoride and acid-fluoride salivary solutions. The fluoride ions could cause
      the breakdown of the protective passivation layer that normally exists on the
      titanium and its alloys, leading to pit corrosion.

PMID- 11996042
TI  - Formation of cartilage matrix proteins by BMP-transfected murine mesenchymal stem
      cells encapsulated in a novel class of alginates.
AB  - Proliferation and differentiation of wild-type, BMP-2 and BMP-4 transfected cells
      of C3H10T1/2, a mouse mesenchymal stem cell line that can differentiate into
      chondrocytes, were studied under monolayer (2D-) and encapsulation (3D-)
      conditions. Cells were encapsulated in a novel class of alginate. The alginate
      was of clinical grade (CG) because of complete removal of mitogenic and cytotoxic
      contaminants by chemical means. Compared to commercial alginates used so far for
      encapsulation it was characterized by ultra-high viscosity (UHV; viscosity of a
      0.1% w/v solution of about 20 cP). In contrast to monolayer cultures,
      proliferation of cells was prevented when the cells were encapsulated in UHV/CG
      alginate at the same suspension density. As revealed by immunohistochemistry and
      quantitative RT-PCR, transfected and wild-type monolayer cells showed synthesis
      of type I collagen after transfer into differentiation medium, while culture in
      an alginate scaffold resulted in an upregulation of type II collagen and other
      hyaline cartilage proteins. BMP-4 transfected cells produced considerably more
      type II collagen than BMP-2 transfected and wild-type cells. BMP-4 transfected
      cells were also characterized by type I collagen production up to Day 10 and
      exhibited transient alkaline phosphatase activity levels that were much higher
      than the peak values observed for the other two cell lines. The coincidence of
      the ALP peak values with downregulation of type I collagen in BMP-4 transfected
      cells suggested that C3H10T1/2 cells differentiate into chondrocytes via a
      chondroprogenitor-like cell.

PMID- 11996043
TI  - PEO-grafting on PU/PS IPNs for enhanced blood compatibility--effect of pendant
      length and grafting density.
AB  - Polyurethane (PU) homopolymers and PU/polystyrene (PS) interpenetrating polymer
      networks (IPNs) were successfully synthesized changing the length of the pendant
      poly(ethylene oxide) (PEO) chains and the grafting density of PEO chains. All the
      PU/PS IPNs had the microphase-separated structures in which the PS-rich phase
      domains were dispersed in the matrix of the PU-rich phase. The domain size
      decreased a little, as the degree of grafting with PEO chains was increased. The
      water swelling ratio increased, and the interfacial energy decreased, as the
      length of the pendant PEO chains, and the grafting density of PEO chains of the
      PEO-grafted PU/PS IPNs were increased, since the mobile hydrophilic pendant PEO
      chains effectively induced and absorbed the water, when they were contacted with
      water. The hydrophilic and highly concentrated pendant PEO chains could easily
      prohibit the adhesion of the fibrinogens and the platelets on the surface, and
      the blood compatibility of IPNs was enhanced by increasing of grafting with PEO
      chains. The adsorption of the fibrinogens and the platelets was suppressed, as
      the length of pendant PEO chains, and the grafting density were increased.

PMID- 11996044
TI  - Usefulness as guided bone regeneration membrane of the alginate membrane.
AB  - Alginate membrane is a new bioabsorbable, guided bone regeneration (GBR)
      membrane, which is placed directly on the surface of the bone defect. It is
      designed to drop a calcium chloride aqueous solution into the bone defect, which
      is filled with sodium alginate aqueous solution. Alginate membrane is an
      excellent agent for this procedure due to its close assimilation to the surface
      of the bone. In this study, we evaluated the short-term biocompatibility of
      alginate membrane in the bone defects of rat tibiae. GBR membrane availability
      was also examined. Consequently, we found that the healing process in bone
      defects covered with an alginate membrane was delayed in comparison with that of
      controls, however, the defect was restored to nearly original condition. In
      contrast, in the controls, bone defect repairs exhibited partitioning as a result
      of connective tissue involvement. Furthermore, we observed a relation between the
      sodium alginate concentration and the rate of absorption of the sodium alginate
      membrane. Absorption of a 1.5% sodium alginate membrane was slow. As a result,
      the compound was not absorbed completely and bone repairs resembled an hourglass.
      Moreover, the inflammatory response was absent surrounding the alginate membrane.
      The present findings suggested that the alginate membrane functions effectively
      as a GBR membrane. In addition, the alginate membrane derived from 3% calcium
      chloride and 1% sodium alginate was most suitable as a GBR membrane.

PMID- 11996045
TI  - Alpha-tricalcium phosphate cement: "in vitro" cytotoxicity.
AB  - Calcium phosphate-based bioceramics have revolutionized orthopedic and dental
      repair of damaged parts of the bone system. Among these materials, calcium
      phosphate-based cements, with hydraulic setting, stand out due to their
      biocompatibility and in situ hardening, which allow easy manipulation and
      adaptation to the shape and dimensions of bone defects. An investigation was made
      of the in vitro cytotoxic effect of calcium phosphate cement based on alpha
      tricalcium phosphate, immersed for different lengths of time in simulated body
      fluid (SBF), based on the ISO-10993 "Biological Evaluation of Medical Devices"
      standard. The culture medium was Chinese hamster ovary (CHO) cells in contact
      with diluted cement extracts. The results revealed that the calcium phosphate
      cement used was cytotoxic and that the material's cytotoxicity decreased the
      longer the cement was immersed in SBF.

PMID- 11996046
TI  - Effects of cloud-point grafting, chain length, and density of PEG layers on
      competitive adsorption of ocular proteins.
AB  - The effects of pinning density, chain length, and 'cloud point' (CP) versus non
      CP grafting conditions have been studied on the ability of polyethylene glycol
      (PEG) layers to minimize adsorption from a multicomponent (lysozyme, human serum
      albumin (HSA), IgG and lactoferrin) protein solution. Methoxy-terminated aldehyde
      PEG (M-PEG, MW 5000) and dialdehyde-PEG (PEG(ald)2, MW 3400) were grafted by
      reductive amination onto two surfaces of different amine group density, generated
      by radiofrequency glow discharge (r.f.g.d.) deposition of n-heptylamine (HA) (low
      density) or allylamine (AlA) (high density) r.f.g.d. polymer layers. The PEG
      graft density was varied also by increasing the temperature and salt (K2SO4)
      content of the grafting solution; it reached a maximum at the CP of the PEGs. The
      CP reaction conditions were critical for producing PEG layers capable of
      minimizing protein adsorption. X-ray photoelectron spectroscopy (XPS) showed that
      under these conditions, PEG(ald)2 produced a thick linear PEG layer, most likely
      by aldol condensation. Protein adsorption was assessed using XPS and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF
      MS) in the surface mode (Surface-MALDI-MS). Coatings grafted at non-CP conditions
      showed some protein adsorption, as did the HA/M-PEG layer grafted at the CP. On
      the other hand, no protein adsorption was detected on the HA/PEG(ald)2, AlA/M
      PEG, and AlA/PEG(ald)2 surfaces when grafted at the CP. Thus, the effects of
      pinning density and chain length are interrelated, but the key factor is
      optimization of PEG chain density by use of the CP conditions, provided that a
      sufficient density of pinning sites exists.

PMID- 11996047
TI  - Pulsed laser deposition of pseudowollastonite coatings.
AB  - Pseudowollastonite (alpha-CaSiO3) is a bioactive ceramic material that induces
      direct bone growth. A process to obtain pseudowollastonite coatings that may be
      applied to implants is described and evaluated in this work. The coatings were
      first deposited on titanium alloy by laser ablation with a pulsed Nd:YAG laser
      tripled in frequency. After deposition, they were submitted to a soft laser
      treatment with a continuous wave Nd:YAG infrared laser. Coatings were
      characterised by X-ray diffractometry, Raman spectroscopy, scanning electron
      microscopy and energy dispersive spectroscopy before and after the laser
      treatment. As-deposited coatings are composed of pseudowollastonite and amorphous
      material. They have a porous structure of gathered grains and poor cohesion.
      After the laser treatment the coatings crystallinity and cohesion are improved.
      The laser treatment also makes the coatings dense and well adhered to the
      substrate. Therefore, this two-step process has been demonstrated as a valuable
      method to coat titanium implants with pseudowollastonite.

PMID- 11996048
TI  - Porous calcium polyphosphate scaffolds for bone substitute applications in vivo
      studies.
AB  - Porous rods (6 mm in length and 4 mm in diameter) of calcium polyphosphate (CPP)
      made by gravity sintering of particles in the size ranges of 45-105, 105-150. and
      150-250 microm and with initial volume percent porosity in the range of 35-45%
      were implanted in the distal femur of New Zealand white rabbits. In an initial
      experiment, four rabbits implanted with rods made from coarse particles (150-250
      microm) were sacrificed at each of the following time points: 2 days, 2 weeks, 6
      weeks and 12 weeks. In a subsequent experiment, 10 rabbits were implanted with
      rods made by sintering 45-105 microm particles and another 10 were made by using
      particles of 105-150 microm. These rabbits were sacrificed at 6 weeks (five
      rabbits) and 1 year (five rabbits). No adverse reaction was found histologically
      at any time point in either experiment. These experiments show that CPP
      macroporous rods can support bone ingrowth and that between 12 weeks and 1 year,
      the amount of bones formed is equivalent to the natural bone volume found at
      similar sites. The degradation of the CPP material is inversely proportional to
      the original particle size and is rapid initially (within the first 6 weeks) and
      slows down thereafter. In conclusion, this material seems to promote rapid bone
      ingrowth and can be tailored to degrade at a given rate in vivo to some degree
      through appropriate selection of the starting particle size.

PMID- 11996049
TI  - Effect of friction on anodic polarization properties of metallic biomaterials.
AB  - The effect of friction on the anodic polarization properties of metallic
      biomaterials in a physiological saline solution was investigated. The current
      density during friction becomes higher than during the static condition. The
      fluctuation range of the current density caused by the destruction and formation
      of passive film was observed. For SUS316L stainless steel and Co-Cr-Mo casting
      alloy, the fluctuation range was observed in the passivity zone. Otherwise, for
      Ti alloys, the fluctuation range was observed in both the activity and passivity
      zones. The decrease of the corrosion potential for Ti alloys due to friction was
      much larger than that of SUS316L stainless steel and Co-Cr-Mo casting alloy. From
      this result, it was considered that in a the frictional environment, the
      stressing zone turned anodic and its periphery cathodic, and corrosion tended to
      progress more than in the static environment. The effect of wear on the anodic
      polarization curves also changed depending on the frictional load, potential zone
      and the pH of the solution. A rapid increase in current density due to corrosion
      starting from the frictional area was found in the Ti-6Al-4V and Ti-15Mo-5Zr-3Al
      alloys containing Al. However, for the new Ti-15Zr-4Nb-4Ta alloy, this rapid
      increase was not seen in the high-potential region. The effect of the lateral
      reciprocal speed was also negligible for the new Ti alloy. It was found that the
      new Ti-15Zr-4Nb-4Ta alloy exhibited excellent corrosion resistance under
      friction.

PMID- 11996050
TI  - A technique to immobilize bioactive proteins, including bone morphogenetic
      protein-4 (BMP-4), on titanium alloy.
AB  - Immobilization of biomolecules on surfaces enables both localization and
      retention of molecules at the cell-biomaterial interface. Since metallic
      biomaterials used for orthopedic and dental implants possess a paucity of
      reactive functional groups, biomolecular modification of these materials is
      challenging. In the present work, we investigated the use of a plasma surface
      modification strategy to enable immobilization of bioactive molecules on a
      "bioinert" metal. Conditions during plasma polymerization of allyl amine on Ti
      6Al-4V were varied to yield 5 ("low")- and 12 ("high")-NH2/nm2. One- and two-step
      carbodiimide schemes were used to immobilize lysozyme, a model biomolecule, and
      bone morphogenetic protein-4 (BMP-4) on the aminated surfaces. Both schemes could
      be varied to control the amount of protein bound, but the one-step method
      destroyed the activity of immobilized lysozyme because of crosslinking. BMP-4 was
      then immobilized using the two-step scheme. Although BMP bound to both low- and
      high-NH2 surfaces was initially able to induce alkaline phosphatase activity in
      pluripotent C3H10T1/2 cells, only high amino group surfaces were effective
      following removal of weakly bound protein by incubation in cell culture medium.

PMID- 11996051
TI  - Effects of organic matrix proteins on the interfacial structure at the bone
      biocompatible nacre interface in vitro.
AB  - The biocompatibility and potential osteoinductivity of nacre have favored its use
      as a bone-grafting material. The present study is to investigate the interfacial
      structure at the bone-nacre interface resulting from organic matrix proteins,
      which emphasizes the mechanism of bone-bonding ability and biocompatibility of
      the shell tissues such as nacre and biogenic calcite. To understand the
      interfacial reaction, the zeta potential measurements, provide for a unique
      method to quantify the actual state of the interface in situ, were used for
      synthetic and biogenic calcium carbonate suspensions with respect to pH and the
      organic matrix as an additive. The zeta potentials and surface charge density
      show that the organic matrix proteins are main charge regulators, resulting in
      the stabilized tissue properties as compared with synthetic crystals. Also, in
      forming calcium carbonate crystals with the additives, the conformation of
      organic matrix has an important role in the understanding of the newly formed
      interfacial structure. The result provides the primary role of the organic matrix
      proteins in controlling the formation of interfacial structure and
      biocompatibility with bone as well as the stability of biogenic tissues. And it
      gives a new insight into the usefulness of zeta potential measurement to describe
      the in vivo interaction between the bone and implants.

PMID- 11996052
TI  - Multileaf collimation of electrons--clinical effects on electron energy
      modulation and mixed beam therapy depending on treatment head design.
AB  - The aim of this study was to explore the possibilities of using multileaf
      collimated electron beams for advanced radiation therapy with conventional
      scattering foil flattened beams. Monte Carlo simulations were performed with the
      aim to improve electron beam characteristics and enable isocentric multileaf
      collimation. The scattering foil positions, monitor chamber thickness, the MLC
      location and the amount of He in the treatment head were optimized for three
      common commercial accelerators. The performance of the three optimized treatment
      head designs was compared for different SSDs in air, at treatment depth in water
      and for some clinical cases. The effects of electron/photon beam matching
      including generalized random and static errors using Gaussian one-dimensional (1
      D) error distributions, and also electron energy modulation, were studied at
      treatment depth in water. The modification of the treatment heads improved the
      electron beam characteristics and enabled the use of multileaf collimation in
      isocentric delivery of both electron and photon beams in a mixed beam IMRT
      procedure.

PMID- 11996053
TI  - Energy spectra, angular spread, fluence profiles and dose distributions of 6 and
      18 MV photon beams: results of monte carlo simulations for a varian 2100EX
      accelerator.
AB  - The purpose of this study is to provide detailed characteristics of incident
      photon beams for different field sizes and beam energies. This information is
      critical to the future development of accurate treatment planning systems. It
      also enhances our knowledge of radiotherapy photon beams. The EGS4 Monte Carlo
      code, BEAM, has been used to simulate 6 and 18 MV photon beams from a Varian
      Clinac-2100EX accelerator. A simulated realistic beam is stored in a phase space
      data file, which contains details of each particle's complete history including
      where it has been and where it has interacted. The phase space files are analysed
      to obtain energy spectra, angular distribution, fluence profile and mean energy
      profiles at the phantom surface for particles separated according to their charge
      and history. The accuracy of a simulated beam is validated by the excellent
      agreement between the Monte Carlo calculated and measured dose distributions.
      Measured depth-dose curves are obtained from depth-ionization curves by
      accounting for newly introduced chamber fluence corrections and the stopping
      power ratios for realistic beams. The study presents calculated depth-dose
      components from different particles as well as calculated surface dose and
      contribution from different particles to surface dose across the field. It is
      shown that the increase of surface dose with the increase of the field size is
      mainly due to the increase of incident contaminant charged particles. At 6 MV,
      the incident charged particles contribute 7% to 21% of maximum dose at the
      surface when the field size increases from 10 x 10 to 40 x 40 cm2. At 18 MV,
      their contributions are up to 11% and 29% of maximum dose at the surface for 10 x
      10 cm2 and 40 x 40 cm2 fields respectively. However, the fluence of these
      incident charged particles is less than 1% of incident photon fluence in all
      cases.

PMID- 11996054
TI  - Direct calibration of a reference standard against the air kerma strength primary
      standard, at 192Ir HDR energy.
AB  - The primary standard of low air kerma rate sources or beams, maintained at the
      Radiological Standards Laboratory (RSL) of the Bhabha Atomic Research Centre
      (BARC), is a 60 cm3 spherical graphite ionization chamber. A 192Ir HDR source was
      standardized at the hospital site in units of air kerma strength (AKS) using this
      primary standard. A 400 cm3 bakelite chamber, functioning as a reference standard
      at the RSL for a long period, at low air kerma rates (compared to external beam
      dose rates), was calibrated against the primary standard. It was seen that the
      primary standard and the reference standard, both being of low Z, showed roughly
      the same scatter response and yielded the same calibration factor for the 400 cm3
      reference chamber, with or without room scatter. However, any likelihood of
      change in the reference chamber calibration factor would necessitate the re
      transport of the primary standard to the hospital site for re-calibration.
      Frequent transport of the primary standard can affect the long-term stability of
      the primary standard, due to its movement or other extraneous causes. The
      calibration of the reference standard against the primary standard at the RSL,
      for an industrial type 192Ir source maintained at the laboratory, showed
      excellent agreement with the hospital calibration, making it possible to check
      the reference chamber calibration at RSL itself. Further calibration procedures
      have been developed to offer traceable calibration of the hospital well
      ionization chambers.

PMID- 11996055
TI  - Towards in vivo monitoring of neutron distributions for quality control of BNCT.
AB  - Dose delivery in boron neutron capture therapy (BNCT) is complex because several
      components contribute to the dose absorbed in tissue. This dose is largely
      determined by local boron concentration, thermal neutron distribution and patient
      positioning. In vivo measurements of these factors would considerably improve
      quality control and safety. During therapy, a y-ray telescope measures the y-rays
      emitted following neutron capture by hydrogen and boron in a small volume of the
      head of a patient. Scans of hydrogen y-ray emissions could be used to verify the
      actual distribution of thermal neutrons during neutron irradiation. The method
      was first tested on different phantoms. These measurements showed good agreement
      with calculations based on thermal neutron distributions derived from a treatment
      planning program and from Monte Carlo N-particle (MCNP) simulations. Next, the
      feasibility of telescope scans during patient irradiation therapy was
      demonstrated. Measurements were reproducible between irradiation fractions. In
      theory, this method can be used to verify the positioning of the patient in vivo
      and the delivery of thermal neutrons in tissue. However, differences between
      measurements and calculations based on a routine treatment planning program were
      observed. These differences could be used to refine the treatment planning.
      Further developments will be necessary for this method to become a standard
      quality control system.

PMID- 11996056
TI  - Theoretical model of internally cooled interstitial ultrasound applicators for
      thermal therapy.
AB  - Interstitial ultrasound applicators for high-temperature thermal therapy are
      currently being developed for treating cancerous and benign disease. Internally
      cooled, direct-coupled (ICDC) applicators, composed of a segmented array of
      cylindrical ultrasound transducers, have demonstrated capabilities of producing
      controllable and conformal heating distributions along the applicator length and
      angular orientation. In this study, 2D transient acoustic and biothermal models
      of ICDC applicators were developed using a mixed implicit and explicit finite
      difference solution with variable node spacing in cylindrical coordinates for
      enhanced speed, stability and accuracy. The model incorporates dynamic behaviour
      of acoustic parameters and blood perfusion as a function of temperature and
      thermal dose. Acoustic intensity distributions were modelled as a composite of
      measured and theoretical intensity distributions. The shape and time evolution of
      temperature contours and thermal lesions for 90 degrees, 200 and 360 degrees
      angularly directional applicators and multi-transducer applicators were modelled
      for heating durations between 1 and 5 min. Model parameters were selected to
      match previously reported ex vivo and in vivo studies of 2.2 mm diameter ICDC
      devices in thigh muscle and liver (15-30 W cm(-2) applied power density, 0.5-5
      min treatment times, 2.8-3.6 cm diameter thermal lesions). The temperatures and
      lethal thermal dose (600 EM43 degrees C) contours calculated using the models
      were in excellent agreement with temperatures and thermal lesion dimensions
      (visible coagulation) determined experimentally. The differences between maximum
      radial depths of coagulation calculated using the r-z and r-theta models were
      small, less than approximately 2 mm for 10-15 mm lesions. There was a strong
      correlation between the calculated 50 degrees C contour and the radial, angular
      and axial lesion dimensions obtained for 3-5 min heating protocols. The models
      developed in this study have significant application in design studies and
      potential future use in treatment planning of ICDC interstitial ultrasound
      thermal therapy.

PMID- 11996057
TI  - Rapid imaging of free radicals in vivo using hybrid FISP field-cycled PEDRI.
AB  - A new pulse sequence for rapid imaging of free radicals is presented which
      combines snapshot imaging methods and conventional field-cycled proton electron
      double resonance imaging (FC-PEDRI). The new sequence allows the number of EPR
      irradiation periods to be optimized to obtain an acceptable SNR and spatial
      resolution of free radical distribution in the final image while reducing the RF
      power deposition and increasing the temporal resolution. Centric reordered phase
      encoding has been employed to counter the problem of rapid decay of the
      Overhauser-enhanced signal. A phase-correction scheme has also been used to
      correct problems arising from instability of the magnetic field following field
      cycling. In vivo experiments were carried out using triaryl methyl free radical
      contrast agent, injected at a dose of 0.214 mmol kg(-1) body weight in
      anaesthetized adult male Sprague-Dawley rats. Transaxial images through the
      abdomen were collected using 1, 2, 4 and 8 EPR irradiation periods. Using 4 EPR
      irradiation periods it was possible to generate free radical distributions of
      acceptable SNR and resolution. The EPR power deposition is reduced by a factor of
      16 and the acquisition time is reduced by a factor of 4 compared to an
      acquisition using the conventional FC-PEDRI pulse sequence.

PMID- 11996058
TI  - Pre-scaled two-parameter Gauss-Newton image reconstruction to reduce property
      recovery imbalance.
AB  - Gauss-Newton image reconstruction in microwave imaging can be formulated in terms
      of a single complex quantity, the wave number squared (k2), with the
      understanding that the relative permittivity and conductivity images can be
      extracted afterwards through a simple constitutive relationship. However, this
      approach ignores the fact that the magnitude of the average real and imaginary
      components can be considerably out of balance depending on the operating
      frequency and tissue characteristics which can inadvertently imbalance the
      process in favour of one parameter over the other. In an effort to achieve
      property recovery which is balanced, we introduce a pre-scaling procedure at the
      property update stage of the reconstruction. Utilization of this concept in
      conjunction with our two-step regularization process for both simulation and
      phantom experiments demonstrates that the penalty term weighting parameters for
      the optimal mean-squared property errors for the two recovered distributions
      (relative permittivity and conductivity) together with that yielding the lowest
      least-squared electric field error coincide only when the scaling is applied. The
      scheme provides a means for simultaneous optimization of the two permittivity and
      conductivity images.

PMID- 11996059
TI  - Paradoxical correlation between signal in functional magnetic resonance imaging
      and deoxygenated haemoglobin content in capillaries: a new theoretical
      explanation.
AB  - Signal increases in functional magnetic resonance imaging (fMRI) are believed to
      be a result of decreased paramagnetic deoxygenated haemoglobin (deoxyHb) content
      in the neural activation area. However, discrepancies in this canonical blood
      oxygenation level dependent (BOLD) theory have been pointed out in studies using
      optical techniques, which directly measure haemoglobin changes. To explain the
      discrepancies, we developed a new theory bridging magnetic resonance (MR) signal
      and haemoglobin changes. We focused on capillary influences, which have been
      neglected in most previous fMRI studies and performed a combined fMRI and near
      infrared spectroscopy (NIRS) study using a language task. Paradoxically, both the
      MR signal and deoxyHb content increased in Broca's area. On the other hand, fMRI
      activation in the auditory area near large veins correlated with a mirror-image
      decrease in deoxyHb and increase in oxygenated haemoglobin (oxyHb), in agreement
      with canonical BOLD theory. All fMRI signal changes correlated consistently with
      changes in oxyHb, the diamagnetism of which is insensitive to MR. We concluded
      that the discrepancy with the canonical BOLD theory is caused by the fact that
      the BOLD theory ignores the effect of the capillaries. Our theory explains the
      paradoxical phenomena of the oxyHb and deoxyHb contributions to the MR signal and
      gives a new insight into the precise haemodynamics of activation by analysing
      fMRI and NIRS data.

PMID- 11996060
TI  - Fuzzy clustering-based segmented attenuation correction in whole-body PET
      imaging.
AB  - Segmented attenuation correction is now a widely accepted technique to reduce
      noise propagation from transmission scanning in positron emission tomography
      (PET). In this paper, we present a new method for segmenting transmission images
      in whole-body scanning. This reduces the noise in the correction maps while still
      correcting for differing attenuation coefficients of specific tissues. Based on
      the fuzzy C-means (FCM) algorithm, the method segments the PET transmission
      images into a given number of clusters to extract specific areas of differing
      attenuation such as air, the lungs and soft tissue, preceded by a median
      filtering procedure. The reconstructed transmission image voxels are, therefore,
      segmented into populations of uniform attenuation based on knowledge of the human
      anatomy. The clustering procedure starts with an overspecified number of clusters
      followed by a merging process to group clusters with similar properties
      (redundant clusters) and removal of some undesired substructures using anatomical
      knowledge. The method is unsupervised, adaptive and allows the classification of
      both pre- or post-injection transmission images obtained using either coincident
      68Ge or single-photon 137Cs sources into main tissue components in terms of
      attenuation coefficients. A high-quality transmission image of the scanner bed is
      obtained from a high statistics scan and added to the transmission image. The
      segmented transmission images are then forward projected to generate attenuation
      correction factors to be used for the reconstruction of the corresponding
      emission scan. The technique has been tested on a chest phantom simulating the
      lungs, heart cavity and the spine, the Rando-Alderson phantom, and whole-body
      clinical PET studies showing a remarkable improvement in image quality, a clear
      reduction of noise propagation from transmission into emission data allowing for
      reduction of transmission scan duration. There was very good correlation (R2 =
      0.96) between maximum standardized uptake values (SUVs) in lung nodules measured
      on images reconstructed with measured and segmented attenuation correction with a
      statistically significant decrease in SUV (17.03% +/- 8.4%, P < 0.01) on the
      latter images, whereas no proof of statistically significant differences on the
      average SUVs was observed. Finally, the potential of the FCM algorithm as a
      segmentation method and its limitations as well as other prospective applications
      of the technique are discussed.

PMID- 11996061
TI  - Determination of the sphere origin for MEG source modelling in temporal regions.
AB  - This paper addresses the choice of spherical volume used in modelling MEG data
      recorded from temporal (auditory cortex) brain regions. We used MRI data sets to
      compute best-fitting spheres for the cranial cavity or inner skull table, and for
      the outer scalp surface. In addition, a 'generic' sphere was computed as the mean
      of the origin coordinates for the cranial spheres. The effects of these sphere
      choices were evaluated by estimating equivalent current dipoles as source
      generators for the M100 component of the auditory evoked field, and comparing the
      goodness-of-fit and 95% confidence volumes. Results indicate that for this area
      the cranial cavity is a better choice of surface to fit than the outer scalp. The
      'generic' sphere results were also superior to those obtained using individual
      outer surfaces.

PMID- 11996062
TI  - The effect of volume currents due to myocardial anisotropy on body surface
      potentials.
AB  - Changes in anterior and posterior body surface potential maps (BSPMs) due to
      myocardial anisotropy were examined using a highly heterogeneous finite element
      model of an adult male subject constructed from segmented magnetic resonance
      images. A total of 23 different tissue types were identified in the whole torso.
      The myocardial fibre orientations in the human heart wall were mapped from the
      fibre orientations of a canine heart which are available in the literature using
      deformable mapping techniques. The current and potential distributions in the
      whole torso were computed using dipolar sources in the septum, apical area, left
      ventricular wall or right ventricular wall. For each dipole x, y, z orientations
      were studied. An adaptive finite element solver was used to compute currents and
      potential distributions in the whole torso with an element size of 0.78 x 0.78 x
      3 mm in the myocardium and larger elements in other parts of the torso. For each
      dipole position two cases were studied. In one case the myocardium was isotropic
      and in the other it was anisotropic. It was found that BSPMs showed a very
      notable difference between the isotropic and the anisotropic myocardium for all
      dipole positions with the largest difference for the apical dipoles. The
      correlation coefficients for the BSPMs between the isotropic and anisotropic
      cases ranged from 0.83 for an apical dipole to 0.99 for an RV wall dipole. These
      results suggest that myocardial fibre anisotropy plays an important role in
      determining the body surface potentials.

PMID- 11996063
TI  - Edema-induced increase in tumour cell survival for 125I and 103Pd prostate
      permanent seed implants--a bio-mathematical model.
AB  - Edema caused by the surgical procedure of prostate seed implantation expands the
      source-to-point distances within the prostate and hence decreases the dose
      coverage. The decrease of dose coverage results in an increase in tumour cell
      survival. To investigate the effects of edema on tumour cell survival, a bio
      mathematical model of edema and the corresponding cell killing by continuous low
      dose rate irradiation (CLDRI) was developed so that tumour cell surviving
      fractions can be estimated in an edematous prostate for both 125I and 103Pd seed
      implants. The dynamic nature of edema and its resolution were modelled with an
      exponential function V(T) = V(p)(1 + M exp(-0.693T/ T(e))) where V(p) is the
      prostate volume before implantation, M is the edema magnitude and T(e) is edema
      half-life (EHL). The dose rate of a radioactive seed was calculated according to
      AAPM TG43, i.e. D = SkAg(r)phi(an)/r2, where r is the distance between a seed and
      a given point. The distance r is now a function of time because of edema. The
      g(r) was approximated as 1/r(0,4) and 1/r(0.8) for 125I and 103Pd, respectively.
      By expanding the mathematical expression of the resultant dose rate in a Taylor
      series of exponential functions of time, the dose rate was made equivalent to
      that produced from multiple fictitious radionuclides of different decay constants
      and strengths. The biologically effective dose (BED) for an edematous prostate
      implant was then calculated using a generalized Dale equation. The cell surviving
      fraction was computed as exp(-alphaBED), where alpha is the linear coefficient of
      the survival curve. The tumour cell survival was calculated for both 125I and
      103Pd seed implants and for different tumour potential doubling time (TPDT) (from
      5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and
      edema half-lives (from 4 days to 30 days). Tumour cell survival increased with
      the increase of edema magnitude and EHL. For a typical edema of a half-life of 10
      days and a magnitude of 50%. the edema increased tumour cell survival by about 1
      and 2 orders of magnitude for 125I and 103Pd seed implants respectively. At the
      extreme (95% edema magnitude and an edema half-life of 30 days), the increase was
      more than 3 and 5 orders of magnitude for 125I and I03Pd seed implants
      respectively. The absolute increases were almost independent of TPDT and the
      prostate edema did not significantly change the effective treatment time. Tumour
      cell survival for prostate undergoing CLDRI using 125I or 103Pd seeds may be
      increased substantially due to the presence of edema caused by surgical trauma.
      This effect appears to be more pronounced for 103Pd than 125I because of the
      shorter half-life of 103Pd. If significant edema is observed post implantation,
      then a boost to the prostate using external beam radiotherapy may be considered
      as a part of the treatment strategy.

PMID- 11996064
TI  - Measurement of backscattered x-ray spectra at the water surface in the energy
      range 60 kV to 120 kV.
AB  - Backscattered x-ray spectra at the water surface have been measured by using a
      small silicon diode detector. The measurements have been made at tube voltages 60
      kV to 120 kV (HVL 2.4-6.1 mm Al) and field sizes 5 x 5 cm2 to 30 x 30 cm2. The
      measured spectra are corrected for detector distortion and for the angular
      dependence of detector efficiency. The obtained backscattered spectrum has a
      lower mean energy and a narrower shape than the primary spectrum. The ratio of
      the mean energy of the backscattered spectrum to that of the primary spectrum is
      between 0.83 and 0.94. The ratio of the spectrum width at 10% of the continuous
      spectrum maximum is between 0.65 and 0.78. The change of spectral shape due to
      the field size is slight. In the high-voltage spectra, the peak due to the
      Compton scattering of tungsten Kalpha x-rays is observed. The backscatter factors
      (BSFs) calculated from the obtained spectra show a satisfactory agreement with
      other studies. The difference between the BSF defined as the ratio of air kerma
      and the BSF defined as the ratio of water kerma is also calculated; the maximum
      difference is 0.43%. The empirical equation showing the relation between the two
      BSFs is presented.

PMID- 11996065
TI  - Magnetic field exposures for UK live-line workers.
AB  - Dosimetry is evaluated for live-line workers exposed to 50 Hz non-uniform
      magnetic fields from typical high-voltage transmission lines in the United
      Kingdom. The configurations involve twin-, triple- and quadruple-conductor
      transmission line bundles. Scenarios include three worker postures for the twin
      and triple bundles, and four postures for the quadruple bundle. The postures are
      selected to simulate worst case scenarios representative of work practices and
      result in highest values of dosimetric measures in critical organs. Only single
      phase bundles are considered, as adjacent bundles of differing phase result only
      in a small reduction of the dosimetric measures. Reported data include various
      measures of the electric field and current density induced in tissues, as well as
      of the current density averaged over 1 cm2 areas normal to the current flow. A
      value of this latter quantity of 10 mA m(-2) is suggested as a threshold for
      neural tissue in the UK and international regulations. Critical tissues
      considered in this study include the retina, spinal cord, brain and cerebrospinal
      fluid. Some discussion is devoted to problems associated with the concept of
      current-density averaging, and two algorithms are considered. For a nominal load
      of 1 kA per subconductor, averaged current densities exceed the guideline bounds,
      only for a small number of postures and bundle configurations, in the brain,
      retina and cerebrospinal fluid. Non-averaged current densities in the
      cerebrospinal fluid exceed the suggested bound for all scenarios modelled, as
      well as in the retina for three postures involving a quadruple bundle.

PMID- 11996066
TI  - Preliminary study on the use of an inhomogeneous anthropomorphic Fricke gel
      phantom and 3D magnetic resonance dosimetry for verification of IMRT treatment
      plans.
AB  - An inhomogeneous anthropomorphic phantom of the human thorax including lungs and
      spine was developed for verification of three-dimensional (3D) intensity
      modulated radiotherapy (IMRT). The phantom and spinal cord were filled with
      undiluted Fricke gel, whereas the lungs were filled with a special low-density
      Fricke gel. Based on a computed tomography scan of the phantom, an intensity
      modulated stereotactic radiotherapy plan for a bronchial carcinoma was calculated
      using an inverse planning system (KonRad, DKFZ Heidelberg, Germany). The plan
      consisted of seven beams delivered in a step and shoot technique out of 67 sub
      fields. Immediately after irradiation 3D magnetic resonance (MR) imaging of the
      phantom was performed using a special pulse sequence for T1 relaxometry. From the
      MR image data maps of the longitudinal relaxation rate R1 = 1/T1 were calculated.
      The R1 maps were converted to dose-proportional image data and compared to
      planning data. Measurement and planning show good agreement in regions of
      standard Fricke gel with an average deviation below 5%. In regions of the low
      density Fricke gel, deviations are higher due to a decreased signal-to-noise
      ratio in the MR measurement. In these areas also a different sensitivity of the
      dose response was observed as compared to standard Fricke gel. The inhomogeneous
      thorax phantom has proven to be a useful pre-clinical tool for 3D methodical
      verifications.

PMID- 11996067
TI  - Correction of count losses due to deadtime on a DST-XLi (SmVi-GE) camera during
      dosimetric studies in patients injected with iodine-131.
AB  - In dosimetric studies performed after therapeutic injection, it is essential to
      correct count losses due to deadtime on the gamma camera. This note describes
      four deadtime correction methods, one based on the use of a standard source
      without preliminary calibration, and three requiring specific calibration and
      based on the count rate observed in different spectrometric windows (20%, 20%
      plus a lower energy window and the full spectrum of 50-750 keV). Experiments were
      conducted on a phantom at increasingly higher count rates to check correction
      accuracy with the different methods. The error was less than +7% with a standard
      source, whereas count-rate-based methods gave more accurate results. On the
      assumption that the model was paralysable, preliminary calibration allowed an
      observed count rate curve to be plotted as a function of the real count rate. The
      use of the full spectrum led to a 3.0% underestimation for the highest activity
      imaged. As count losses depend on photon flux independent of energy, the use of
      the full spectrum during measurement allowed scatter conditions to be taken into
      account. A protocol was developed to apply this correction method to whole-body
      acquisitions.

PMID- 11996068
TI  - An introduction to medical imaging with coherent terahertz frequency radiation.
AB  - Methods have recently been developed that make use of electromagnetic radiation
      at terahertz (THz) frequencies, the region of the spectrum between millimetre
      wavelengths and the infrared, for imaging purposes. Radiation at these
      wavelengths is non-ionizing and subject to far less Rayleigh scatter than visible
      or infrared wavelengths, making it suitable for medical applications. This paper
      introduces THz pulsed imaging and discusses its potential for in vivo medical
      applications in comparison with existing modalities.

PMID- 11996069
TI  - Thrombectomy before hepatic resection for hepatocellular carcinoma with a tumor
      thrombus extending to the inferior vena cava.
AB  - Tumor thrombi of hepatocellular carcinoma occasionally invade into the inferior
      vena cava (IVC) through the hepatic vein. Once the tumor thrombus is dislodged,
      severe and lethal complications, such as pulmonary infarction, can develop. We
      successfully operated on a hepatocellular carcinoma (HCC) patient with a tumor
      thrombus extending to the IVC through the right hepatic vein. To avoid dislodging
      the thrombus during surgery, a thrombectomy using selective hepatic vascular
      exclusion was performed before a hepatic resection, which is the most dangerous
      procedure to dislodge the thrombus.

PMID- 11996070
TI  - Sural artery flap: a dependable solution in lower leg and foot soft tissue
      reconstruction.
AB  - For a variety of reasons, mainly anatomical, the skin and soft tissue defects in
      the lower leg and foot remain a challenging problem for reconstructive surgeons.
      Simple skin grafts, local random flaps, cross leg flaps, microvascular flaps,
      etc., have been used to tackle this difficult problem. Although to date, probably
      the most popular flaps are the fasciocutaneous flaps based on one of the three
      major vessels of the leg. We have used a fasciocutaneous flap based on sural
      artery, accompanying the sural nerve to cover moderate-sized defects in 12 cases.
      This eliminates the sacrifice of major vessels, and the procedure is easy, quick,
      and dependable.

PMID- 11996071
TI  - Influence of hepatocyte growth factor secreted from fibroblasts on the growth and
      invasion of scirrhous gastric cancer.
AB  - The objective of this study was to show that hepatocyte growth factor (HGF) and
      HGF receptor (c-met protein) play an important role in the cancer growth and
      infiltration in scirrhous gastric cancer. The expression level of c-met protein
      was examined in 90 cases of advanced gastric cancer using anti-c-met antibody. Co
      cultivation of each of four gastric cancer cell lines with gastric fibroblasts
      was performed using a double chamber method. The expression rate of c-met was
      79.5% in type 4 tumors, significantly higher than in other types. The expression
      rates were 63.6% in undifferentiated-type cancer and 36.3% in differentiated-type
      cancer. Co-cultivation of undifferentiated-type cancer with fibroblasts showed a
      significantly higher HGF concentration than fibroblasts cultured alone. The
      growth in three undifferentiated-type cancers was accelerated by an addition of
      rhHGF and by co-cultivation with fibroblasts and was inhibited by anti-HGF
      antibody. Moreover rhHGF stimulated the invasion activity of undifferentiated
      cancer cell lines. These findings suggested that gastric fibroblasts in scirrhous
      cancer stimulate tumor growth and invasion through activation of the HGF/c-met
      system.

PMID- 11996072
TI  - Evaluation of Ranson, Glasgow, APACHE-II, and APACHE-O criteria to predict
      severity in acute biliary pancreatitis.
AB  - There are a few prospective studies assessing the severity of acute pancreatitis
      with exclusive criteria for biliary etiology. In a cohort prospective study,
      Ranson (biliary etiology), Glasgow-modified, APACHE-II, and APACHE-O prognostic
      criteria were assessed in 65 patients with acute biliary pancreatitis (ABP).
      Local complications such as necrosis with fluid peripancreatic collection (3
      patients), fluid collection with pancreas enlargement (3 patients), pancreatic
      fistula (1 patients), and pancreatic pseudocyst (1 patients); and organic failure
      such as renal (5 patients), hemodynamic (3 patients), and respiratory (3
      patients) were found. The prognostic criteria performance, according to parameter
      number or positive variables evidenced that relative risk (RR) varied from 4.7 to
      11.2, sensibility from 33.3% to 83.3%, specificity from 79.2% to 98.1%, positive
      predictive value from 45.0% to 83.3%, negative predictive value from 86.4% to
      95.5%, and accuracy from 78.5% to 89.6%. In isolation, most important parameters
      correlated to severity included white blood cell count >18,000/mm3, lactate
      dehydrogenase (LDH) >400 UI/l, 10% drop of the hematocrit, serum calcium <8
      mg/dl, increase of urea nitrogen >2 mg/dl, aspartate aminotransferase (AST) >200
      mg/dl, LDH >600 UI/l, white blood cell count >15,000/mm3, urea >45 mg/dl,
      arterial pH < or = 7.33 or > or = 7.49, creatinin < or = 0.6 or > or = 1.4,
      hematocrit < or = 30 or > or = 45.9, white blood cell count < or = 3,000/mm3 or >
      or = 14,900/mm3. Ranson, Glasgow-modified, APACHE-II, and APACHE-O acute biliary
      pancreatitis severity criteria all present good sensibility and excellent
      specificity.

PMID- 11996073
TI  - Is there any benefit of preservation of the spleen in distal pancreatectomy?
AB  - For a pancreatic body or tail tumor, distal pancreatectomy with splenectomy (DPS)
      is a standard operation. Spleen-preserving distal pancreatectomy (SPDP) was
      introduced in order to preserve the organ and thus provide the patient with a
      better quality of life. Clinical data were compared between 38 Japanese patients
      with DPS and 9 with SPDP for benign tumors or tumor-like lesions at the body or
      tail of the pancreas at preoperative, early postoperative (< 3 months after
      operation), and late postoperative periods (>6 months after operation). The
      preoperative findings were not different between the two groups except for the
      significantly higher serum amylase levels in the SPDP group. Operation time,
      operative blood loss, and length of postoperative hospital stay were not
      different between the two groups. Pancreatic fistula occurred in 3 (8%) of the 38
      patients in the DPS group and in 1 (11%) of the 9 patients in the SPDP group,
      abdominal abscess in 5 (13%) of the 38 patients in the DPS group and none (0%) in
      the 9 patients in the SPDP group. At short-term, clinical findings were not
      different between the two groups except for a significantly greater platelet
      count in the DPS group than in the SPDP group (46.8 x 10(4)/microl versus 29.6 x
      10(4)/microl, P = 0.0081). At long-term after the operation, clinical findings,
      including the platelet count, were not different between the two groups. Computed
      tomography revealed a pseudocyst in 9 (53%) of 17 patients examined in the DPS
      group and in 3 (75%) of 4 patients examined in the SPDP group at short-term after
      operation. All patients with pseudocysts were asymptomatic. Two asymptomatic
      patients (one in the DPS group and one in the SPDP group) first developed a
      pseudocyst at long-term after the operation. The alteration of glucose tolerance
      was similar between the two groups. Postoperative pancreatic exocrine function
      (the N-benzol-L-tyrosyl-p-aminobenzoic acid test) was not different between the
      two groups. These data suggest that SPDP with preservation of the splenic vessels
      can be satisfactorily performed without elongating operative time and
      postoperative hospital stay or increasing risk of postoperative complications,
      with the exception of increased platelet count in the DPS group at short-term
      after the operation. Thus, SPDP is worth considering as one of the options for
      the treatment of benign lesions of the body or tail of the pancreas.

PMID- 11996074
TI  - Two cases of penile necrosis in diabetics with end-stage renal failure.
AB  - Distal penile necrosis associated with renal failure is a rare entity; only a few
      cases have been reported in the literature. Penile necrosis can frequently be a
      difficult management problem, the etiology of which is infectious, traumatic, or
      vascular. Physiological abnormalities are usually found in association with this
      condition, including diabetes, hyperparathyroidism, and peripheral vascular
      disease. Penile necrosis is a poor prognostic factor associated with high
      morbidity. We report two cases of this condition, presenting the clinical and
      pathophysiological background.

PMID- 11996075
TI  - Bilateral hydroureter and hydronephrosis causing renal failure due to a
      procidentia uteri: a case report.
AB  - We report a case of complete uterine prolapse that resulted in bilateral
      hydroureter, hydronephrosis, and renal dysfunction. The nonoperative reduction of
      the prolapse with a vaginal pessary reversed the obstructive uropathy and
      ameliorated renal function. The lower urinary tract should be imaged in patients
      with complete uterine prolapse. If present, obstructive uropathy should be
      relieved by the reduction of the prolapse before irreversible renal damage
      occurs.

PMID- 11996076
TI  - Prophylactic antibiotics after severe trauma: more is not better.
AB  - After severe trauma, physicians frequently use multiple antibiotics for prolonged
      periods of time to prevent sepsis, based on intuition rather than scientific
      evidence. Over a 1-year period (January-December 1999) we included prospectively
      112 critically injured patients who required an operation and/or chest tube
      insertion and stayed for more than 2 days in the intensive care unit (ICU). Of
      these patients, 46 received a single prophylactic antibiotic for 24 hours (group
      SING+SHORT), and 66 received one or more prophylactic antibiotics for more than
      24 hours (group MULT+LONG), based on physician discretion. Twenty-seven outcome
      parameters were collected to compare the effect of the different prophylactic
      antibiotic regimens. The two groups were similar in regard to overall injury
      severity, age, gender, mechanism of injury, and physiologic condition on
      admission. However, more SING+SHORT patients had an abdominal operation (83%
      versus 62%, P = 0.02), and more MULT+LONG patients had an orthopedic operation
      (35% versus 15%, P = 0.03). There was no difference in sepsis (41% versus 42%, P
      = 1.0), organ failures (37% versus 50%, P = 0.18), mortality (7% versus 12%, P =
      0.52), ICU stay (14 +/- 2.5 versus 16 +/- 2 days, P = 0.57), hospital stay (26 +/
      3 versus 28 +/- 2 days, P = 0.53), or any other outcome parameter. Independent
      risk factors for sepsis were blunt mechanism of trauma, Injury Severity Score >
      or = 25, and more than two units of blood transfused over the first 24 hours, but
      not the amount of prophylactic antibiotics given. In conclusion, we found that 24
      hour prophylaxis with a single broad-antibiotic is as effective as prophylaxis
      for longer periods of time with multiple spectrum antibiotics for critically
      injured patients at high risk for sepsis.

PMID- 11996077
TI  - Primary sarcoma of the inferior vena cava: review of diagnosis, treatment, and
      outcomes in a case series.
AB  - Leiomyosarcoma of the inferior vena cava is a rare mesenchymal tumor. The
      diagnostic approach, based on general guidelines of oncologic surgery, seems to
      be relatively routine; specific aspects of treatment, including vascular
      reconstruction, depend on tumor stage, grade, and location. In this report, the
      management of this disease in 5 patients is summarized and the literature is
      reviewed. A thorough diagnostic assessment includes sonography, computed
      tomography, angiography or duplex ultrasonography, perioperative pathohistologic
      examination, and appropriate differential diagnosis. Radical resection is
      associated with the best outcome and long-term survival. In this series, 4 of 5
      patients underwent tumor resection. In 2 patients, the disease was classified as
      R0. Another patient had R1 status found at resection and underwent postoperative
      radiation after the tumor bed was marked intraoperatively. She has remained
      stable since treatment. One patient died of pulmonary metastases 32 months after
      primary R1 tumor resection. The 5th patient has been stable since diagnosis;
      resection was not possible because of severe accompanying diseases and because
      consent for surgical intervention could not be obtained from the patient. There
      is reasonable hope that leiomyosarcoma of the inferior vena cava can be treated
      successfully, even in advanced stages, with novel antineoplastic drugs and
      radiotherapeutic protocols. However, general treatment recommendations have not
      yet been compiled.

PMID- 11996078
TI  - Cecal diverticulitis: a case report and review of the current literature.
AB  - We report a case of a female patient with a picture of "atypical appendicitis,"
      with 3 days of abdominal pain, localized to the right lower quadrant with no
      nausea, vomiting, diarrhea, or anorexia. On examination she was febrile to 38.4
      degrees C, had tenderness at McBurney's point, and a leukocyte count of 11,200. A
      computerized axial tomography (CAT) scan was obtained showing changes consistent
      with appendicitis. On laparoscopic exploration the patient was found to have
      cecal masses. Definitive surgical treatment was deferred until after adequate
      evaluation of the colon. Postoperative colonoscopy demonstrated cecal
      diverticulitis. Management of cecal diverticulitis found during laparotomy for
      presumed appendicitis has included right hemicolectomy, ileocolic resection or
      appendectomy, and conservative treatment with antibiotics. The laparoscopic
      approach in a patient with an equivocal history and physical examination allows
      for definitive workup of inflammatory cecal masses found during surgery for
      appendicitis.

PMID- 11996079
TI  - Video-assisted total thyroidectomy.
AB  - During the last few years, video-assisted neck surgery (VANS) became one option
      for thyroid and parathyroid surgery. Reports on VANS were limited to partial
      resection of the thyroid gland. In this study, we described total thyroidectomy
      in a patient with Graves' disease. The patient had a thyrotoxic periodic
      paralysis and methimazole-induced hepatic toxicity as well as hepatitis B virus.
      Two incisions of 3.5 and 3 cm were placed in the right and left subclavicular
      regions, respectively. A third incision of 0.5 cm was made just to the right of
      the midline for the camera. Devascularization of the thyroid gland was performed
      by using ultrasonically activated shear. Tubal drains were inserted on both
      sides. The patient suffered from temporary postoperative hoarseness with the
      voice but had a normal calcium level. The drains were removed on the first
      postoperative day. The use of VANS may provide a new method for total
      thyroidectomy with a better cosmetic outcome.

PMID- 11996080
TI  - Intractable obstructive shock as a result of isolated cardiac metastases: a case
      report.
AB  - Cardiac metastases are uncommon and difficult to diagnose clinically; thus, they
      are most often found only at autopsy. Here we present a case of isolated right
      atrial cardiac metastasis found 7 weeks after the resection of the primary tumor,
      which was an adenocarcinoma of the lung. The patient presented with intractable
      obstructive shock, caused by a ball-valve effect of the atrial lesion that
      prevented forward blood flow from the right atrium. Computed tomography (CT)
      scans and echocardiograms failed to detect the lesion, and the patient died 2
      weeks later. An autopsy revealed a large, isolated right atrial metastatic
      adenocarcinoma.

PMID- 11996081
TI  - Polylysine and polyornithine gene transfer complexes: a study of complex
      stability and cellular uptake as a basis for their differential in-vitro
      transfection efficiency.
AB  - Gene transfer vectors formed between the cationic polyamino acid, poly-(L)
      omithine (PLO) and plasmid DNA (pDNA) have demonstrated superior transfection
      efficiency (up to x 10-fold) compared to equivalent polylysine-based systems in
      vitro. The mechanism(s) underlying this observation remains to be elucidated. We
      previously reported no significant difference in colloidal particle size or zeta
      potential of polycation/pDNA complexes formed with poly-(L)-lysine (PLL), poly
      (D)-lysine (PDL) or PLO. Here we report spectrofluorometric analysis indicating
      that PLO condenses pDNA at lower charge (+/-) ratios than PLL or PDL (cf. 0.8:1,
      1.2:1 and 1.5:1). Moreover, PLO/pDNA complexes proved more stable to disruption
      by the polyanions, poly-(L)-aspartic acid (PAA) and heparin. There were no
      qualitative differences in the ability of the polycations to protect complexed
      pDNA from enzymatic degradation both in the presence and in the absence of
      polyanions. The superior transfection efficiency of PLO/pDNA complexes did not
      appear to be mediated by an increased cellular delivery of pDNA. The data
      suggests a greater affinity of PLO for pDNA as an important parameter for the
      observed superior in-vitro transfection efficiency.

PMID- 11996082
TI  - Microparticle-mediated transfection of non-phagocytic cells in vitro.
AB  - DNA-loaded microparticles represent an attractive delivery system to target
      professional antigen presenting cells (APC) for the delivery of DNA vaccines.
      Microparticles exhibiting a positively charged surface were prepared by the
      incorporation of two selected cationic polymers into a poly(D, L-lactide-co
      glycolide) polymer (PLGA) core. The toxicity of the different formulations was
      checked in two cell lines and was found to be comparable to plain PLGA particles.
      Increased toxicity of some formulations was observed in primary macrophages
      (Mphi) with high phagocytosis activity. Plasmid DNA was efficiently adsorbed to
      the microparticle surfaces, and the different formulations were checked for their
      transfection efficiency in phagocytic and non-phagocytic cells. Interestingly,
      the most pronounced gene transfer efficiency was observed in a non-phagocytic 293
      cell line when compared to a macrophage cell line and primary Mphi. Possible
      mechanisms include the dissociation of DNA-polymer complex and subsequent
      transfection of the cells. Microscopic observation of fluorescent-labeled DNA in
      primary Mphi revealed large amounts of DNA entering the cells, but no detectable
      DNA inside the nuclei. We conclude that phagocytic professional APC represent a
      group of cells, which is especially difficult to transfect when compared to other
      cell types. The administration of DNA in vivo is likely to predominantly result
      in the transfection of non-lymphoid cells unless there is a possibility to
      provide efficient targeting and trafficking of the DNA to the nucleus of
      professional APC. Although DNA-loaded PEI and DAEM microparticles resulted in
      significant transfection of cells, toxicity and transfection efficiency was not
      superior to that of DNA complexed with soluble PEI and DAEM.

PMID- 11996083
TI  - In vitro and in vivo effect of HPMA copolymer-bound doxorubicin targeted to
      transferrin receptor of B-cell lymphoma 38C13.
AB  - N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing the anticancer
      agent doxorubicin and targeted to the transferrin receptor either with anti-mouse
      CD71 monoclonal antibody (mAb) or with transferrin were synthesized to evaluate
      their binding and anti-proliferative activity in vitro and anti-tumor potential
      against 38C13 B-cell lymphoma in vivo. Both the doxorubicin and the targeting
      moieties were bound to HPMA copolymer chain by aminolysis via a Gly-Phe(D,L)-Leu
      Gly spacer to ensure controlled intracellular release of the conjugated drug. We
      demonstrated that HPMA copolymer-bound doxorubicin targeted to the transferrin
      receptor with anti-mouse CD71 mAb strongly retards tumor growth, prolongs the
      survival and completely cures three out of nine experimental mice with
      established 38C13 tumors. The conjugate targeted with transferrin was less
      effective in vitro as well as in vivo. It completely cured only one out of seven
      experimental mice. Free or non-targeted HPMA copolymer-bound doxorubicin showed
      only a mild anti-tumor effect within the therapeutic schedule used. In vitro,
      HPMA copolymer-bound doxorubicin targeted with anti-mouse CD71 mAb shows
      approximately 4-fold higher cytotoxic effect than HPMA copolymer-bound
      doxorubicin targeted with transferin and 9-fold higher cytotoxic effect than non
      targeted HPMA copolymer-bound doxorubicin.

PMID- 11996084
TI  - Permeability characteristics of calu-3 human bronchial epithelial cells: in vitro
      in vivo correlation to predict lung absorption in rats.
AB  - The goal of this study was to evaluate the permeability characteristics of Calu
      3, human bronchial epithelial cells to passive and actively transported drugs and
      to correlate the data with other in vitro models and rat lung absorption in vivo.
      Air-interface cultured Calu-3 cells grown on collagen-coated permeable filter
      supports formed "tight" polarized and well differentiated cell monolayers with
      apical microvilli and tight-junctional complexes. Within 8-10 days, cell
      monolayers developed trans-epithelial electrical resistance (TEER) > 1000 ohm cm2
      and potential difference about 11-16 mV. Solute permeability was dependent on
      lipophilicity, and inversely related to molecular size. Calu-3 cells actively
      transported amino acids, nucleosides and dipeptide analogs, but not organic
      anions, organic cations or efflux pump substrates. The permeability
      characteristics of Calu-3 cells correlated well with primary cultured rabbit
      tracheal epithelial cells in vitro (r2 = 0.91), and the rate of drug absorption
      from the rat lung in vivo (r2 = 0.94). The absorption predicted from the
      regression equation correlated well with observed values. In conclusion, in vitro
      in vivo correlation studies indicate that the Calu-3 cell culture model is a
      potentially useful model to predict absorption of inhalation delivery drug
      candidates.

PMID- 11996085
TI  - Superior chemotherapeutic efficacy of amphotericin B in tuftsin-bearing liposomes
      against Leishmania donovani infection in hamsters.
AB  - Chemotherapeutic efficacy of the amphotericin B (Amp B), which is the drug of
      choice for treatment of the leishmanial infections (kala-azar) that become
      resistant to the conventional chemotherapy using antimonials, has been examined
      in the Leishmania donovani infected hamsters after encapsulating the drug in
      tuftsin-free as well as tuftsin-bearing liposomes. The activity was significantly
      increased (p < 0.05) by delivering Amp B in tuftsin-free liposomes. This
      antileishmanial effect of the liposomized Amp B was further increased (p < 0.05)
      by grafting the natural macrophage-activator tetrapeptide, tuftsin (Thr-Lys-Pro
      Arg), on the liposome's surface. This could possibly be attributed to both the
      enhanced drug tolerance after liposomization as well as to the increased uptake
      of tuftsin-bearing Amp B-laden liposomes by the macrophages. In addition to the
      increased efficacy, encapsulation of Amp B in the tuftsin-bearing liposomes also
      enhanced the drug accessibility to areas (e.g. bone marrow) that are otherwise
      inaccessible to the free drug. These results further demonstrate the usefulness
      of tuftsin-bearing liposomes as drug vehicles in treatment of the macrophage
      based infections that have been reviewed recently (Agrawal, A.K. and Gupta, C.M.
      (2000). Tuftsin-bearing liposomes in treatment of macrophage-based infections,
      Adv. Drug Deliv. Rev., 41, 135-146).

PMID- 11996086
TI  - Differential behaviour of fluid liposomes toward mammalian epithelial cells and
      bacteria: restriction of fusion to bacteria.
AB  - Previous work demonstrated that fluid liposomes developed in our laboratory are
      able to fuse with bacterial outer membranes. This fusion improved the penetration
      and activity of liposome-encapsulated antibiotics and antisense oligonucleotides
      into the bacterial cells. Because it is anticipated that fluid liposome
      encapsulated antibiotics will be administered by aerosols to patients with
      chronic pulmonary infections or cystic fibrosis (CF), we conducted comparative
      studies in E. coli, P. aeruginosa and human lung epithelial cells using lipid
      mixing assays to investigate the possibility that fluid liposomes might fuse with
      surrounding epithelial cells. After a 2 h incubation at 4 and 37 degrees C, no
      fusion between fluid liposomes and human lung epithelial cells was observed,
      whereas mean levels of 71 and 37% of fusion were observed at 37 degrees C with E.
      coli and P. aeruginosa cells, respectively. No fusion was observed at 4 degrees C
      in any cells. A kinetic study where temperature was gradually increased from 7 to
      37 degrees C indicated that the fusion process in the two bacteria starts between
      28 and 31 degrees C with a mean fusion rate of 0.60%/min at 31 degrees C to reach
      1.18%/min at 37 degrees C. The present work suggests that it is unlikely that
      fluid liposomes fuse with host cells lining the human respiratory tract and
      further elucidates the fusogenic properties of fluid liposomes with respect to
      prokaryotes and eukaryotes.

PMID- 11996087
TI  - Effect of delivery route on pulmonary response to oncostatin M.
AB  - The effect of delivery route on lung tissue response to oncostatin M (OM) was
      evaluated in isolated perfused rat lung (IPRL) and normal human bronchial
      epithelial cell line BEAS-2B in vitro models. In this study, the extent of
      induction of the cytokine IL-6 by OM was examined as evidence for local
      pharmacological activity in response to OM in lung tissue. OM stimulated dose
      dependent release of IL-6 in both BEAS-2B cells and IPRL after exposure of either
      the apical (AP) or basolateral (BL) side of the epithelium. The increase in IL-6
      was rapid, beginning 2 h after dosing, and sustained over 48 h. Similar amounts
      of IL-6 were released to both AP and BL sides of BEAS-2B cells, regardless of the
      side of OM dosing. However, in IPRL the extent of response of IL-6 induction to
      OM was always higher at the dosing side. In addition, airway dosing of OM
      resulted in an overall lower IL-6 response than perfusate dosing, which may
      result from the low rate of OM transport (<1%/h) across pulmonary epithelium. We
      conclude that the route of delivery significantly affects the overall extent of
      the pharmacological response to OM, with a lesser and more localized response
      after airway delivery to the lung.

PMID- 11996088
TI  - In vitro and in vivo evaluations of dihydroquinoline- and dihydroisoquinoline
      based targetor moieties for brain-specific chemical delivery systems.
AB  - Brain-targeted delivery of various drugs can be successfully achieved by chemical
      delivery systems (CDS) that contain a 1,4-dihydropyridine-based redox targetor
      moiety and undergo a sequential metabolism. However, the susceptibility of this
      moiety toward hydration in acidic media may limit the shelf-life of such
      compounds in aqueous formulation. Here, a systematic investigation of the
      chemical stability toward oxidation and hydration of ester and amide derivatives
      of 3-substituted 1,4-dihydropyridine, 1,4-dihydroquinoline, and 4-substituted 1,2
      dihydroisoquinoline is reported, together with the in vitro stability and in vivo
      (rat) distribution of isoquinoline-based testosterone and hydrocortisone chemical
      delivery systems, which were selected as having the most suitable acid-resistant
      targetor moieties.

PMID- 11996089
TI  - By-passing of P-glycoprotein using immunoliposomes.
AB  - The over-expression of MDR1 P-glycoprotein has been associated with the
      development of multidrug-resistance in cancer cells. Methods used to overcome
      multidrug-resistance often involve the co-administration of inhibitors of P
      glycoprotein. Here, we test the hypothesis that an immunoliposome-based drug
      delivery system may be used as an alternative approach to overcome multidrug
      resistance since immunoliposomes penetrate target cells by receptor-mediated
      endocytosis which allows to by-pass membrane-associated P-glycoprotein. Targeting
      of immunoliposomes was achieved by the use of an anti-transferrin receptor
      monoclonal antibody (OX26 mAb). Incorporation of radiolabelled digoxin within
      OX26-immunoliposomes enhanced cellular uptake of digoxin by a factor of 25 in
      immortalised RBE4 rat brain capillary endothelial cells. Uptake of liposomal
      digoxin was insensitive to ritonavir, a P-glycoprotein inhibitor, and was reduced
      in presence of increasing free concentrations of OX26 mAb or nocodazole, a
      reversible inhibitor of endocytosis. In contrast, uptake of free digoxin was
      enhanced by a factor of 1.8 in presence of ritonavir and was insensitive to OX26
      mAb or nocodazole. Cellular uptake and intracellular accumulation of liposomal
      digoxin (55% internalisation within 30 min) was demonstrated by acid wash of the
      cells and was confirmed by confocal microscopy studies. Endosomal release to the
      cytosol of propidium iodide loaded immunoliposomes was shown. These in vitro
      studies suggest that immunoliposome-based drug delivery systems can be used to by
      pass P-glycoprotein and thus deliver drugs to the cytosol of a target cell.

PMID- 11996090
TI  - Targeting of doxorubicin to the urinary bladder of the rat shows increased
      cytotoxicity in the bladder urine combined with an absence of renal toxicity.
AB  - Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder
      carcinoma may be useful, since these agents generally have a low degree of
      urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug
      doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid
      sensitive cis-aconityl linker. All free amino groups of the lysozyme were used
      for drug attachment to achieve intact excretion of the doxorubicin-aconityl
      lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be
      regenerated through acidification of the urine. First, the doxorubicin-aconityl
      lysozyme conjugate was tested in rats for its target specificity and general
      toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin
      or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of
      doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/-
      3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on
      heart, liver and lung but caused severe renal damage (proteinuria, N
      acetylglucosaminidase excretion and glomerulosclerosis). None of the rats
      injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second,
      we tested whether doxorubicin could be released from the conjugate in the bladder
      through acidification of the urine and if the released doxorubicin could still
      exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated
      doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1)
      and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was
      released from the conjugate in the group with acidified urine (15 +/- 7% versus
      1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH
      group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a
      specific delivery of doxorubicin to the urinary bladder combined with a reduced
      toxicity of doxorubicin in the kidneys can be achieved by coupling this anti
      tumor drug to the low-molecular weight protein lysozyme via an acid-labile
      linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved
      by acidification of the urine. This technology, after further optimization, may
      provide an interesting tool for the treatment of bladder carcinoma.

PMID- 11996091
TI  - Order-disorder structural transitions in synthetic filaments of fast and slow
      skeletal muscle myosins under relaxing and activating conditions.
AB  - In the previous study (Podlubnaya et al., 1999, J. Struc. Biol. 127, 1-15) Ca2+
      induced reversible structural transitions in synthetic filaments of pure fast
      skeletal and cardiac muscle myosins were observed under rigor conditions (
      Ca2+/+Ca2+). In the present work these studies have been extended to new more
      order-producing conditions (presence of ATP in the absence of Ca2+) aimed at
      arresting the relaxed structure in synthetic filaments of both fast and slow
      skeletal muscle myosin. Filaments were formed from column-purified myosins
      (rabbit fast skeletal muscle and rabbit slow skeletal semimebranosusproprius
      muscle). In the presence of 0.1 mM free Ca2+, 3 mM Mg2+ and 2 mM ATP (activating
      conditions) these filaments had a spread structure with a random arrangement of
      myosin heads and subfragments 2 protruding from the filament backbone. Such a
      structure is indistinguishable from the filament structures observed previously
      for fast skeletal, cardiac (see reference cited above) and smooth (Podlubnaya et
      al., 1999, J. Muscle Res. Cell Motil. 20, 547-554) muscle myosins in the presence
      of 0.1 mM free Ca2+. In the absence of Ca2+ and in the presence of ATP (relaxing
      conditions) the filaments of both studied myosins revealed a compact ordered
      structure. The fast skeletal muscle myosin filaments exhibited an axial
      periodicity of about 14.5 nm and which was much more pronounced than under rigor
      conditions in the absence of Ca2+ (see the first reference cited). The slow
      skeletal muscle myosin filaments differ slightly in their appearance from those
      of fast muscle as they exhibit mainly an axial repeat of about 43 nm while the
      14.5 nm repeat is visible only in some regions. This may be a result of a
      slightly different structural properties of slow skeletal muscle myosin. We
      conclude that, like other filaments of vertebrate myosins, slow skeletal muscle
      myosin filaments also undergo the Ca2+-induced structural order-disorder
      transitions. It is very likely that all vertebrate muscle myosins possess such a
      property.

PMID- 11996092
TI  - Motifs of the caldesmon family.
AB  - Seven highly conserved regions were found in caldesmon molecules from various
      sources using the multiple sequence alignment method. Their localization
      coincides with regions where the binding sites to other proteins were postulated.
      Less conserved and highly divergent regions of the sequences are described as
      well. These results could refine the planning of caldesmon gene manipulations and
      accelerate the precise localization of binding sites in the caldesmon molecule
      and, as a consequence, this could help to elucidate its function in smooth muscle
      contraction.

PMID- 11996093
TI  - Heme synthesis in yeast does not require oxygen as an obligatory electron
      acceptor.
AB  - In a previous paper (Krawiec, Z., Bilinski, T., Schuller, C. & Ruis, H., 2000,
      Acta Biochim. Polon. 47, 201-207) we have shown that catalase T holoenzyme is
      synthesized in the absence of oxygen after treatment of anaerobic yeast cultures
      with 0.3 M. NaCl, or during heat shock. This finding suggests that heme moiety of
      the enzyme can either be formed de novo in the absence of oxygen, or derives from
      the preexisting heme pool present in cells used as inoculum. The strain bearing
      hem1 mutation, resulting in inability to form delta-aminolevulinate (ALA), the
      first committed precursor of heme, was used in order to form heme-depleted cells
      used as inocula. The cultures were supplemented with ALA at the end of anaerobic
      growth prior the stress treatment. The appearance of active catalase T in the
      stressed cells strongly suggests that heme moiety of catalase T is formed in the
      absence of oxygen. This finding suggests the necessity to reconsider current
      opinions concerning mechanisms of heme synthesis and the role of heme as an
      oxygen sensor.

PMID- 11996094
TI  - The DFF40/CAD endonuclease and its role in apoptosis.
AB  - The sequential generation of large-scale DNA fragments followed by
      internucleosomal chromatin fragmentation is a biochemical hallmark of apoptosis.
      One of the nucleases primarily responsible for genomic DNA fragmentation during
      apoptosis is called DNA Fragmentation Factor 40 (DFF40) or Caspase-activated
      DNase (CAD). DFF40/CAD is a magnesium-dependent endonuclease specific for double
      stranded DNA that generates double strand breaks with 3'-hydroxyl ends. DFF40/CAD
      is activated by caspase-3 that cuts the nuclease's inhibitor DFF45/ICAD. The
      nuclease preferentially attacks chromatin in the internucleosomal linker DNA.
      However, the nuclease hypersensitive sites can be detected and DFF40/CAD is
      potentially involved in large-scale DNA fragmentation as well. DFF40/CAD-mediated
      DNA fragmentation triggers chromatin condensation that is another hallmark of
      apoptosis.

PMID- 11996095
TI  - Further studies on the role of phospholipids in determining the characteristics
      of mitochondrial binding sites for type I hexokinase.
AB  - Previous work has indicated that two types (A and B) of binding sites for
      hexokinase exist, but in different proportions, on brain mitochondria from
      various species. Hexokinase is readily solubilized from Type A sites by glucose 6
      phosphate (Glc-6-P), while hexokinase bound to Type B sites remains bound even in
      the presence of Glc-6-P. Type A:Type B ratios are approximately 90:10, 60:40,
      40:60, and 20:80 for brain mitochondria from rat, rabbit, bovine and human brain,
      respectively. The present study has indicated that MgCl2-dependent partitioning
      of mitochondrially bound hexokinase into a hydrophobic (Triton X-114) phase is
      generally correlated with the proportion of Type B sites. This partitioning
      behavior is sensitive to phospholipase C, implying that the factor(s) responsible
      for conferring hydrophobic character is(are) phospholipid(s). Substantial
      differences were also seen in the resistance of hexokinase, bound to brain
      mitochondria from various species, to solubilization by Triton X-100, Triton X
      114, or digitonin. This resistance increased with proportion of Type B sites.
      Enrichment of bovine brain mitochondria in acidic phospholipids
      (phosphatidylserine or phosphatidylinositol), but not phosphatidylcholine or
      phosphatidylethanolamine, substantially increased solubilization of the enzyme
      after incubation at 37 degrees C. Collectively, the results imply that the Type A
      and Type B sites are located in membrane domains of different lipid composition,
      the Type A sites being in domains enriched in acidic phospholipids which lead to
      greater susceptibility to solubilisation by Glc-6-P.

PMID- 11996096
TI  - Theoretical studies of binding modes of two covalent inhibitors of cysteine
      proteases.
AB  - Physiological and pathological roles of cysteine proteases make them important
      targets for inhibitor development. Although highly potent inhibitors of this
      group of enzymes are known, their major drawback is a lack of sufficient
      specificity. Two cysteine protease covalent inhibitors, viz. (i) Z-RL-deoxo-V
      peptide-epoxysuccinyl hybrid, and (ii) Z-RLVG-methyl-, have been developed and
      modeled in the catalytic pocket of papain, an archetypal thiol protease. A number
      of configurations have been generated and relaxed for each system using the AMBER
      force field. The catalytic pockets S3 and S4 appear rather elusive in view of the
      observed inhibitors' flexibility. This suggest rather limited chances for the
      development of selective structure-based inhibitors of thiol proteases, designed
      to exploit differences in the structure of catalytic pockets of various members
      of this family.

PMID- 11996097
TI  - Structure and biosynthesis of human salivary mucins.
AB  - Human salivary glands secrete two types of mucins: oligomeric mucin (MG1) with
      molecular mass above 1 MDa and monomeric mucin (MG2) with molecular mass of 200
      250 kDa. Monomers of MG1 and MG2 contain heavily O-glycosylated tandem repeats
      located at the central domain of the molecules. MG1 monomers are linked by
      disulfide bonds located at sparsely glycosylated N- and C-end. MG1 are
      synthesized by mucous cells and MG2 by the serous cells of human salivary glands.

PMID- 11996098
TI  - Proteoglycans of human umbilical cord arteries.
AB  - Proteoglycans (PGs) were dissociatively extracted from human umbilical cord
      arteries (UCAs) with 4 M guanidine hydrochloride containing Triton X-100 and
      protease inhibitors, purified by Q-Sepharose anion exchange chromatography and
      lyophilized. They were analysed by gel filtration, SDS/PAGE and agarose gel
      electrophoresis before and after treatment with chondroitinase ABC. It was found
      that the PG preparation was especially enriched in chondroitin/dermatan sulphate
      PGs. The predominant PG fraction included small PGs that emerged from Sepharose
      CL-2B with Kav = 0.74. Their molecular mass, estimated by SDS/PAGE, was 160-200
      kDa and 90-150 kDa, i.e. it was typical for biglycan and decorin, respectively.
      Treatment with chondroitinase ABC yielded the core proteins of 45 and 47 kDa,
      characteristic for both small PGs. Remarkable amounts of the 45 kDa protein were
      detected in non-treated PG samples, suggesting the presence of free core proteins
      of biglycan and decorin. Large PGs were present in lower amounts. In intact form
      they were eluted from Sepharose CL-2B with Kav = 0.17 and 0.43. Digestion with
      chondroitinase ABC yielded the core proteins with a molecular mass within the
      range of 180-360 kDa but predominant were the bands of 200, 250 and 360 kDa. The
      large PGs probably represent various forms of versican or perlecan bearing
      chondroitin sulphate chains.

PMID- 11996099
TI  - Phenobarbital-induced expression of cytochrome P450 genes.
AB  - In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene
      by polycyclic aromatic hydrocarbons, the molecular mechanism by which
      phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains
      unknown; no receptor for these chemicals has been found to date. However, in the
      last 5 years PB-responsive sequences have been identified in the 5' flanking
      regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU)
      of CYP2B gene family members contain two potential nuclear receptor binding sites
      (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear
      factors that regulate PBRU activity have not yet been characterized. It seems
      that PB may activate multiple nuclear orphan receptors to induce various CYP
      genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR
      and PXR, respectively. It is also possible that the pleiotropic effects of PB
      can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a
      variety of nuclear receptor binding motifs. The induction of cytochromes P450 may
      result in interactions between xenobiotics and in the interference of xenobiotic
      metabolism and endogenous signalling pathways.

PMID- 11996100
TI  - Toxicological and cytophysiological aspects of lanthanides action.
AB  - Lanthanides, also called rare-earth elements, are an interesting group of 15
      chemically active, mainly trivalent, f-electronic, silvery-white metals. In fact,
      lanthanides are not as rare as the name implies, except for promethium, a
      radioactive artificial element not found in nature. The mean concentrations of
      lanthanides in the earth's crust are comparable to those of life-important
      elements like iodine, cobalt and selenium. Many lanthanide compounds show
      particular magnetic, catalytic and optic properties, and that is why their
      technical applications are so extensive. Numerous industrial sources enable
      lanthanides to penetrate into the human body and therefore detailed toxicological
      studies of these metals are necessary. In the liver, gadolinium selectively
      inhibits secretion by Kupffer cells and it decreases cytochrome P450 activity in
      hepatocytes, thereby protecting liver cells against toxic products of xenobiotic
      biotransformation. Praseodymium ion (Pr3+) produces the same protective effect in
      liver tissue cultures. Cytophysiological effects of lanthanides appear to result
      from the similarity of their cationic radii to the size of Ca2+ ions. Trivalent
      lanthanide ions, especially La3+ and Gd3+, block different calcium channels in
      human and animal cells. Lanthanides can affect numerous enzymes: Dy3+ and La3+
      block Ca2+-ATPase and Mg2+-ATPase, while Eu3+ and Tb3+ inhibit calcineurin. In
      neurons, lanthanide ions regulate the transport and release of synaptic
      transmitters and block some membrane receptors, e.g. GABA and glutamate
      receptors. It is likely that lanthanides significantly and uniquely affect
      biochemical pathways, thus altering physiological processes in the tissues of
      humans and animals.

PMID- 11996101
TI  - Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed
      to tobacco smoke.
AB  - Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke
      obtained from non-filter cigarettes. During the exposure, concentration of
      tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/m3
      air). The efficacy of exposure was assessed by measuring urine nicotine and
      cotinine levels. Cigarette smoke did not change total cytochrome P450 and b5
      protein levels in any of the organs studied, and most of these organs did not
      show any changes in the activity of reductases associated with these cytochromes.
      Following exposure to tobacco smoke, fetal rat liver expressed CYP2B1/2 protein;
      in newborns (day 1) both liver and lung showed CYP2B1/2 protein expression and
      very low pentoxyresorufin O-dealkylase activity. Western blot analysis of adult
      liver, lung, heart, but not of brain microsomes, showed that tobacco smoke
      induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was
      lower in the livers and hearts of pregnant females. In the rat and human
      placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke
      induced expression at the protein level. This study shows clearly that the
      expression of CYP2B1/2, which metabolizes nicotine and some drugs and activates
      carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific
      regulatory mechanisms.

PMID- 11996102
TI  - Influence of acetaminophen and trichloroethylene on liver cytochrome P450
      dependent monooxygenase system.
AB  - The aim of the study was to evaluate the effect of acetaminophen (APAP) and/or
      trichloroethylene (TRI) on the liver cytochrome P450-dependent monooxygenase
      system, CYP2E1 and CYP1A2 (two important P450 isoforms), and liver glutathione
      (GSH) content in rats. Rats were given three different doses of APAP (250, 500
      and 1000 mg/kg b...) and then the above-mentioned parameters were measured for 48
      h. The lowest APAP dose produced small changes in the cytochrome P450 content of
      liver. At 500 mg/kg APAP increased the cytochrome P450 content to 230% of the
      control. The inductive effect was seen at 1000 mg/kg dose but at 24 h and later.
      NADPH-cytochrome P450 reductase activity was the highest after the lowest dose of
      APAP, while after the highest dose it was equal to the control value. TRI
      increased both the cytochrome P450 content and the NADPH-cytochrome P450
      reductase activity. When TRI was combined with APAP, both these parameters
      increased in the first hours of observation, but they returned to the control
      values at 24 h. When APAP was given at 250 mg/kg, GSH levels decreased to 55% of
      the control at 8 h and returned to the control values at 24 h. The higher doses
      of APAP decreased GSH levels more than the lowest dose, but after 24 h GSH levels
      did not differ from those of the control. When TRI was given at 250 mg/kg, the
      GSH levels decreased to 68% of the control at 2 h and then they increased
      gradually and tended to exceed the control values at 48 h. The effect of TRI
      combined with APAP on the level of GSH was virtually the same as that of APAP
      alone given at 500 mg/kg.

PMID- 11996103
TI  - Arterial ketone index in assessing liver function and its detoxicative capability
      after ischemia-reperfusion injury.
AB  - Arterial ketone index (AKBR) which is the ratio of acetoacetic acid to 3
      hydroxybutyric acid in the arterial blood, is believed to reflect the
      mitochondrial reduction potential of hepatocytes and general energy state of the
      liver. In the presented paper we challenged this hypothesis by analysing the
      correlation between AKBR and the results of typical liver blood tests (AspAT,
      AlAT, LDH, CRP) and biotransforming potential of the liver (cytochromes P450, b5
      and their corresponding NADPH and NADH reductases) in the model of ischemia
      reperfusion injury of rat liver. The results were compared with histochemical
      analysis of distribution and activity of SDH, LDH and G-6-Pase, the key marker
      enzymes of the liver. We have shown that, except in the case of acute phase
      protein (CRP), a decrease in AKBR correlated well with the increase of the level
      of indicator enzymes in serum. Histochemical analysis also confirmed that AKBR
      correlates with the degree of damage to hepatocytes during early stage of
      reperfusion after 60 min of liver ischemia. In the Spearman test, AKBR was
      significantly correlated with the changes in cytochrome P450 content and its
      NADPH reductase activity which indicates a high sensitivity of this test. We
      conclude that the decrease of AKBR value reflects the impairment of basic energy
      pathways and detoxicative capability of the liver.

PMID- 11996105
TI  - Expression of beta1-integrins and N-cadherin in bladder cancer and melanoma cell
      lines.
AB  - Changes in the expression of integrins and cadherins might contribute to the
      progression, invasion and metastasis of transitional cell cancer of the bladder
      and of melanomas. The expression of alpha5 (P < 0.001), alpha2 and beta1 (P <
      0.05 - P < 0.001) integrin subunits in melanoma cells from noncutaneous
      metastatic sites (WM9, A375) were significantly increased as compared to
      cutaneous primary tumor (WM35) and metastatic (WM239) cell lines. These
      differences might be ascribed to the invasive character of melanoma cells and
      their metastasis to the noncutaneous locations. The significantly heterogeneous
      expression of beta1 integrin subunit in two malignant bladder cancer cell lines
      (T24 and Hu456) and nonsignificant differences in the expression of alpha2,
      alpha3, and alpha5 subunits between malignant and non-malignant human bladder
      cell lines do not allow an unanimous conclusion on the role of these intergrin
      subunits in the progression of transitional cancer of bladder. The adhesion
      molecule, expressed in all studied melanoma and bladder cell lines, that reacted
      with anti-Pan cadherin monoclonal antibodies was identified as N-cadherin except
      in the HCV29 non-malignant ureter cell line. However, neither this nor any other
      bladder or melanoma cell line expressed E-cadherin. The obtained results imply
      that the replacement of E-cadherin by N-cadherin accompanied by a simultaneous
      increase in expression of alpha2, alpha3 and alpha5 integrin subunits clearly
      indicates an increase of invasiveness of melanoma and, to a lesser extent, of
      transitional cell cancer of bladder. High expression of N-cadherin and alpha5
      integrin subunit seems to be associated with the most invasive melanoma
      phenotype.

PMID- 11996104
TI  - Ligands of peroxisome proliferator-activated receptor-gamma increase the
      generation of vascular endothelial growth factor in vascular smooth muscle cells
      and in macrophages.
AB  - Peroxisome proliferator-activated receptors-gamma (PPARgamma) are ligand
      inducible transcription factors of the nuclear hormone receptor superfamily. We
      examined the effect of PPARgamma activation on the generation of vascular
      endothelial growth factor (VEGF), one of the major angiogenic agents. Rat
      vascular smooth muscle cells (VSMC) and murine macrophages RAW264.7 were
      incubated for 24 h with PPARgamma activators: prostaglandin J2 and ciglitazone.
      PPARgamma were expressed in VSMC and RAW cells and their activity was upregulated
      in the presence of PGJ2 and ciglitazone. Incubation of the cells with PPARgamma
      activators significantly augmented the release of VEGF protein into the media,
      both in resting and in IL-1beta- or LPS-stimulated cultures. The higher protein
      generation was connected with the increased expression of mRNA and
      transcriptional activation of VEGF promoter. We conclude that the activation of
      PPARgamma upregulates the generation of VEGF and may be involved in the
      regulation of angiogenesis.

PMID- 11996106
TI  - Elevation of the adenylate pool in rat cardiomyocytes by S-adenosyl-L-methionine.
AB  - Rapid resynthesis of the adenylate pool in cardiac myocytes is important for
      recovery of contractility and normal function of regulatory mechanisms in the
      heart. Adenosine and adenine are thought to be the most effective substrates for
      nucleotide synthesis, but the possibility of using other compounds has been
      studied very little in cardiomyocytes. In the present study, the effect of S
      adenosyl-L-methionine (SAM) on the adenylate pool of isolated cardiomyocytes was
      investigated and compared to the effect of adenine and adenosine. Adult rat
      cardiomyocytes were isolated using the collagenase perfusion technique. The cells
      were incubated in the presence of adenine derivatives for 90 min followed by
      nucleotide determination by HPLC. The concentrations of adenine nucleotides
      expressed in nmol/mg of cell protein were initially 22.1 +/- 1.4, 4.0 +/- 0.3 and
      0.70 +/- 0.08 for ATP, ADP and AMP, respectively (n = 10, +/- S.E.M.), and the
      total adenylate pool was 26.8 +/- 1.6. In the presence of 1.25 mM SAM in the
      medium, the adenylate pool increased by 5.2 +/- 0.4 nmol/mg of cell protein, but
      only if 1 mM ribose was additionally present in the medium. No changes were
      observed with SAM alone. A similar increase (by 4.9 +/- 0.6 nmol/mg protein) was
      observed after incubation with 1.25 mM adenine plus 1 mM ribose, but no increase
      was observed if ribose was omitted. Adenosine at 0.1 or 1.25 mM concentrations
      also caused an increase in the adenylate pool (by 5.2 +/- 1.0 and 5.2 +/- 0.9
      nmol/mg protein, respectively), which in contrast to the SAM or adenine was
      independent of the additional presence of ribose. Thus, S-adenosyl-L-methionine
      could be used as a precursor of the adenylate pool in cardiomyocytes, which is as
      efficient in increasing the adenylate pool after 90 min of incubation as
      adenosine or adenine. Nucleotide synthesis from SAM involves the formation of
      adenine as an intermediate with its subsequent incorporation by adenine
      phosphoribosyltransferase.

PMID- 11996107
TI  - p53 codon 72 polymorphism in cervical cancer patients and healthy women from
      Poland.
AB  - A polymorphism at codon 72 of gene p53 results in the presence of either arginine
      or proline at this position. We investigated the distribution of p53 codon 72
      polymorphism in cervical cancer patients and a control group of healthy women
      from Poland. Our results do not confirm the hypothesis that the p53 codon
      polymorphism could play a role as a factor for squamous carcinoma of the cervix.

PMID- 11996108
TI  - Multidrug resistance-associated protein--reduction of expression in human
      leukaemia cells by antisense phosphorothioate olignucleotides.
AB  - Multidrug resistance-associated protein (MRP1) causes cellular drug resistance in
      several cancer cell lines. In this paper we show that antisense oligonucleotides
      decrease MRP1 expression in human leukaemia cells. We investigated biological
      activity of a series of 12 linear phosphorothioate oligonucleotides,
      complementary to several regions of MRP1 mRNA. The oligonucleotides were
      administered to leukaemia HL60/ADR cells overexpressing MRP1 protein. Then, the
      level of MRP1 mRNA was determined by means of semiquantitative RT-PCR and the
      protein level by reaction with specific monoclonal antibodies. Some of the
      investigated antisense oligonucleotides decrease the expression level of the MRP1
      protein by 46% and its mRNA level by 76%.

PMID- 11996109
TI  - Plant ureases: roles and regulation.
AB  - Both urea and urease were subjects of early scientific investigations. Urea was
      the first organic molecule to be synthesized and jack bean urease was the first
      enzyme ever to be crystallized. About 50 years later it was shown to be the first
      nickel metalloenzyme. Since then, nickel-dependent ureases have been isolated
      from many bacteria, fungi and higher plants. They have similar structures and
      mechanisms of catalysis. A urease apoenzyme needs to be activated. This process
      requires participation of several accessory proteins that incorporate nickel into
      the urease forming catalytic site. In this review, ureases from various organisms
      are briefly described and the similarities of their structures discussed.
      Moreover, the significance of urea recycling in plants is explained and recent
      literature data about the function and activation of plant ureases are presented.

PMID- 11996110
TI  - Reactive oxygen species are formed in cell culture media.

PMID- 11996111
TI  - The response of L5178Y lymphoma sublines to oxidative stress: antioxidant
      defence, iron content and nuclear translocation of the p65 subunit of NF-kappaB.
AB  - We examined the response to hydrogen peroxide of two L5178Y (LY) sublines which
      are inversely cross-sensitive to hydrogen peroxide and X-rays: LY-R cells are
      radio-resistant and hydrogen peroxide-sensitive, whereas LY-S cells are
      radiosensitive and hydrogen peroxide-resistant. Higher initial DNA breaks and
      higher iron content (potentially active in the Fenton reaction) were found in the
      hydrogen peroxide sensitive LY-R cells than in the hydrogen peroxide resistant LY
      S cells, whereas the antioxidant defence of LY-R cells was weaker. In particular,
      catalase activity is twofold higher in LY-S than in LY-R cells. The content of
      monobromobimane-reactive thiols is 54% higher in LY-S than in LY-R cells. In
      contrast, the activity of glutathione peroxidase (GPx) is about two times higher
      in LY-R than in LY-S cells; however, upon induction with selenium the activity
      increases 15.6-fold in LY-R cells and 50.3-fold in LY-S cells. Altogether, the
      sensitivity difference is related to the iron content, the amount of the initial
      DNA damage, as well as to the efficiency of the antioxidant defence system.
      Differential nuclear translocation of p65-NF-kappaB in LY sublines is due to the
      more efficient antioxidant defence in LY-S than in LY-R cells.

PMID- 11996112
TI  - The reactions of hypochlorous acid, the reactive oxygen species produced by
      myeloperoxidase, with lipids.
AB  - Myeloperoxidase (MPO), an abundant enzyme in phagocytes, has been implicated in
      the pathogenesis of various inflammatory diseases including atherosclerosis. The
      major oxidant produced by MPO, hypochlorous acid (HOCl), is able to modify a
      great variety of biomolecules by chlorination and/or oxidation. In this paper the
      reactions of lipids (preferentially unsaturated fatty acids and cholesterol) with
      either reagent HOCl or HOCl generated by the MPO-hydrogen peroxide-chloride
      system are reviewed. One of the major issues has been whether the reaction of
      HOCl with lipids of low density lipoprotein (LDL) yields predominantly
      chlorohydrins or lipid hydroperoxides. Electrospray mass spectrometry provided
      direct evidence that chlorohydrins rather than peroxides are the major products
      of HOCl- or MPO-treated LDL phosphatidylcholines. Nevertheless lipid peroxidation
      is a possible alternative reaction of HOCl with polyunsaturated fatty acids if an
      additional radical source such as pre-formed lipid hydroperoxides is available.
      In phospholipids carrying a primary amino group such as phosphatidylethanolamine
      chloramines are the preferred products compared to chlorohydrins. Cholesterol can
      be converted by HOCl to great variety of oxysterols besides three isomers of
      chlorohydrins. For the situation in vivo it appears that the type of reaction
      occurring between HOCl and lipids would very much depend on the circumstances,
      e.g. the pH and the presence of radical initiators. The biological effects of
      lipid chlorohydrins are not yet well understood. It has been shown that
      chlorohydrins of both unsaturated fatty acids as well as of cholesterol may cause
      lysis of target cells, possibly by disruption of membrane structures.

PMID- 11996113
TI  - Peroxidation of proteins and lipids in suspensions of liposomes, in blood serum,
      and in mouse myeloma cells.
AB  - There is growing evidence that proteins are early targets of reactive oxygen
      species, and that the altered proteins can in turn damage other biomolecules. In
      this study, we measured the effects of proteins on the oxidation of liposome
      phospholipid membranes, and the formation of protein hydroperoxides in serum and
      in cultured cells exposed to radiation-generated hydroxyl free radicals.
      Lysozyme, which did not affect liposome stability, gave 50% protection when
      present at 0.3 mg/ml, and virtually completely prevented lipid oxidation at 10
      mg/ml. When human blood serum was irradiated, lipids were oxidized only after the
      destruction of ascorbate. In contrast, peroxidation of proteins proceeded
      immediately. Protein hydroperoxides were also generated without a lag period in
      hybrid mouse myeloma cells, while at the same time no lipid peroxides formed.
      These results are consistent with the theory that, under physiological
      conditions, lipid membranes are likely to be effectively protected from randomly
      generated hydroxyl radicals by proteins, and that protein peroxyl radicals and
      hydroperoxides may constitute an important hazard to biological systems under
      oxidative stress.

PMID- 11996114
TI  - Mitochondria recycle nitrite back to the bioregulator nitric monoxide.
AB  - Nitric monoxide (NO) exerts a great variety of physiological functions. L
      Arginine supplies amino groups which are transformed to NO in various NO-synthase
      active isoenzyme complexes. NO-synthesis is stimulated under various conditions
      increasing the tissue of stable NO-metabolites. The major oxidation product found
      is nitrite. Elevated nitrite levels were reported to exist in a variety of
      diseases including HIV, reperfusion injury and hypovolemic shock. Denitrifying
      bacteria such as Paracoccus denitrificans have a membrane bound set of
      cytochromes (cyt cd1, cyt bc) which were shown to be involved in nitrite
      reduction activities. Mammalian mitochondria have similar cytochromes which form
      part of the respiratory chain. Like in bacteria quinols are used as reductants of
      these types of cytochromes. The observation of one-e- divergence from this redox
      couple to external dioxygen made us to study whether this site of the respiratory
      chain may also recycle nitrite back to its bioactive form NO. Thus, the aim of
      the present study was therefore to confirm the existence of a reductive pathway
      which reestablishes the existence of the bioregulator NO from its main metabolite
      NO2-. Our results show that respiring mitochondria readily reduce added nitrite
      to NO which was made visible by nitrosylation of deoxyhemoglobin. The adduct
      gives characteristic triplet-ESR-signals. Using inhibitors of the respiratory
      chain for chemical sequestration of respiratory segments we were able to identify
      the site where nitrite is reduced. The results confirm the ubiquinone/cyt be1
      couple as the reductant site where nitrite is recycled. The high affinity of NO
      to the heme-iron of cytochrome oxidase will result in an impairment of
      mitochondrial energy-production. "Nitrite tolerance" of angina pectoris patients
      using NO-donors may be explained in that way.

PMID- 11996115
TI  - Lipid radicals: properties and detection by spin trapping.
AB  - Unsaturated lipids are rapidly oxidized to toxic products such as lipid
      hydroperoxides, especially when transition metals such as iron or copper are
      present. In a Fenton-type reaction Fe2+ converts lipid hydroperoxides to the very
      short-lived lipid alkoxyl radicals. The reaction was started upon the addition of
      Fe2+ to an aqueous linoleic acid hydroperoxide (LOOH) emulsion and the spin trap
      in the absence of oxygen. Even when high concentrations of spin traps were added
      to the incubation mixture, only secondary radical adducts were detected, probably
      due to the rapid re-arrangement of the primary alkoxyl radicals. With the
      commercially available nitroso spin trap MNP we observed a slightly immobilized
      ESR spectrum with only one hydrogen splitting, indicating the trapping of a
      methinyl fragment of a lipid radical. With DMPO or 5-diethoxyphosphoryl-5-methyl
      1-pyrroline N-oxide (DEPMPO) adducts were detected with carbon-centered lipid
      radical, with acyl radical, and with the hydroxyl radical. We also synthesized
      lipophilic derivatives of the spin trap DEPMPO in order to detect lipid radical
      species generated in the lipid phase. With all spin traps studied a lipid-derived
      carbon-centered radical was obtained in the anaerobic incubation system Fe2+/LOOH
      indicating the trapping of a lipid radical, possibly generated as a secondary
      reaction product of the primary lipid alkoxyl radical formed. Under aerobic
      conditions an SOD-insensitive oxygen-centered radical adduct was formed with
      DEPMPO and its lipophilic derivatives. The observed ESR parameters were similar
      to those of alkoxyl radical adducts, which were independently synthesized in
      model experiments using Fe3+-catalyzed nucleophilic addition of methanol or t
      butanol to the respective spin trap.

PMID- 11996116
TI  - Peroxynitrite mediated linoleic acid oxidation and tyrosine nitration in the
      presence of synthetic neuromelanins.
AB  - Peroxynitrite-mediated linoleic acid oxidation and tyrosine nitration were
      analysed in the presence of synthetic model neuromelanins: dopamine (DA) 
      melanin, cysteinyldopamine (CysDA) -melanin and various DA/CysDA copolymers. The
      presence of melanin significantly decreased the amount of 3-nitrotyrosine formed.
      This inhibitory effect depended on the type and concentration of melanin polymer.
      It was found that incorporation of CysDA-derived units into melanin attenuated
      its protective effect on tyrosine nitration induced by peroxynitrite. In the
      presence of bicarbonate, the melanins also inhibited 3-nitrotyrosine formation in
      a concentration dependent manner, although the extent of inhibition was lower
      than in the absence of bicarbonate. The tested melanins inhibited peroxynitrite
      induced formation of linoleic acid hydroperoxides, both in the absence and in the
      presence of bicarbonate. In the presence of bicarbonate, among the oxidation
      products appeared 4-hydroxynonenal (HNE). CysDA-melanin inhibited the formation
      of HNE, while DA-melanin did not affect the aldehyde level. The results of the
      presented study suggest that neuromelanin can act as a natural scavenger of
      peroxynitrite.

PMID- 11996117
TI  - Two-electron reduction of nitroaromatic compounds by Enterobacter cloacae NAD(P)H
      nitroreductase: description of quantitative structure-activity relationships.
AB  - Enterobacter cloacae NAD(P)H:nitroreductase catalyzes the reduction of a series
      of nitroaromatic compounds with steady-state bimolecular rate constants (kcat/Km)
      ranging from 10(4) M(-1) s(-1) to 10(7) M(-1) s(-1), and oxidizing 2 moles NADH
      per mole mononitrocompound. Oxidation of excess NADH by polynitrobenzenes
      including explosives 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenyl-N
      methylnitramine (tetryl), has been observed as a slower secondary process,
      accompanied by O2 consumption. This type of 'redox cycling' was not related to
      reactions of nitroaromatic anion-radicals, but was caused by the autoxidation of
      relatively stable reaction products. The logs kcat/Km of all the compounds
      examined exhibited parabolic dependence on their enthalpies of single-electron-
      or two-electron (hydride) reduction, obtained by quantum mechanical calculations.
      This type of quantitative structure-activity relationships shows that the
      reactivity of nitroaromatics towards E. cloacae nitroreductase depends mainly on
      their hydride accepting properties, but not on their particular structure, and
      does not exclude the possibility of multistep hydride transfer.

PMID- 11996118
TI  - Generation of *OH initiated by interaction of Fe2+ and Cu+ with dioxygen;
      comparison with the Fenton chemistry.
AB  - Iron and copper toxicity has been presumed to involve the formation of hydroxyl
      radical (*OH) from H2O2 in the Fenton reaction. The aim of this study was to
      verify that Fe2+-O2 and Cu+-O2 chemistry is capable of generating *OH in the
      quasi physiological environment of Krebs-Henseleit buffer (KH), and to compare
      the ability of the Fe2+-O2 system and of the Fenton system (Fe2+ + H2O2) to
      produce *OH. The addition of Fe2+ and Cu+ (0-20 microM) to KH resulted in a
      concentration-dependent increase in *OH formation, as measured by the salicylate
      method. While Fe3+ and Cu2+ (0-20 microM) did not result in *OH formation, these
      ions mediated significant *OH production in the presence of a number of reducing
      agents. The *OH yield from the reaction mediated by Fe2+ was increased by
      exogenous Fe3+ and Cu2+ and was prevented by the deoxygenation of the buffer and
      reduced by superoxide dismutase, catalase, and desferrioxamine. Addition of 1
      microM, 5 microM or 10 microM Fe2+ to a range of H2O2 concentrations (the Fenton
      system) resulted in a H2O2-concentration-dependent rise in *OH formation. For
      each Fe2+ concentration tested, the *OH yield doubled when the ratio
      [H2O2]:[Fe2+] was raised from zero to one. IN CONCLUSION: (i) Fe2+-O2 and Cu+-O2
      chemistry is capable of promoting *OH generation in the environment of oxygenated
      KH, in the absence of pre-existing superoxide and/or H2O2, and possibly through a
      mechanism initiated by the metal autoxidation; (ii) The process is enhanced by
      contaminating Fe3+ and Cu2+; (iii) In the presence of reducing agents also Fe3+
      and Cu2+ promote the *OH formation; (iv) Depending on the actual [H2O2]:[Fe2+]
      ratio, the efficiency of the Fe2+-O2 chemistry to generate *OH is greater than
      or, at best, equal to that of the Fe2+-driven Fenton reaction.

PMID- 11996119
TI  - In vitro effects of ozone on human erythrocyte membranes: an EPR study.
AB  - The effects of ozone at different concentrations (10, 30, 45 g/m3) on fluidity
      and thermotropic properties of erythrocyte membranes were investigated by EPR
      using two spin probes: 5-doxylstearic acid (5-DSA) and 16-doxylstearic acid (16
      DSA). The effect of ozone on the erythrocyte membrane fluidity was a dose
      dependent process. The ozone at concentration of 10 g/m3 caused rigidization of
      the membrane while at concentration of 45 g/m3 increased fluidity both on the
      surface and in the deeper hydrocarbon region of the membrane. Temperature
      transitions close to the polar heads region (monitored by 5-DSA) were not
      sensitive to an increase in ozone concentration. In the case of 16-DSA, low
      temperature thermotropic transition (around 20 degrees C) gradually decreased
      with the increase of ozone concentration. High temperature transition (around 40
      degrees C) significantly differed at the ozone concentration of 10 g/m3 and 45
      g/m3, being higher and lower, respectively, as compared to untreated cells. For
      the ozone concentration of 45 g/m3 the disappearance of the low temperature break
      and the appearance of two breaks at 37 degrees C and 16 degrees C were observed.

PMID- 11996120
TI  - Coupling of mitochondrial translation with the formation of respiratory complexes
      in yeast mitochondria.
AB  - In contrast to most other eukaryotic organisms, yeast can survive without
      respiration. This ability has been exploited to investigate nuclear genes
      required for expression of mitochondrial DNA. Availability of complete
      Saccharomyces cerevisiae genomic sequence has provided additional help in
      detailed molecular analysis. Seven of the eight major products encoded by
      mitochondrial DNA are hydrophobic subunits of respiratory complexes in the inner
      membrane. Localization of the translation process in the same cellular
      compartment ensures synthesis of mitochondrially encoded proteins near sites of
      their assembly into multimeric respiratory complexes. Association of
      mitochondrial ribosomes with the membrane is mediated by mRNA-specific
      translational activators, that are involved in the recognition of initiation
      codon. The newly synthesized mitochondrial proteins are transferred to membrane
      by a specific export system. This review discusses the role of membrane-localized
      factors responsible for quality control and turnover of mitochondrially
      synthesized subunits as well as for assembly of respiratory complexes.

PMID- 11996121
TI  - The KRR1 gene encodes a protein required for 18S rRNA synthesis and 40S ribosomal
      subunit assembly in Saccharomyces cerevisiae.
AB  - The newly discovered Saccharomyces cerevisiae gene KRR1 (YCL059c) encodes a
      protein essential for cell viability. Krr1p contains a motif of clustered basic
      amino acids highly conserved in the evolutionarly distant species from yeast to
      human. We demonstrate that Krr1p is localized in the nucleolus. The KRR1 gene is
      highly expressed in dividing cells and its expression ceases almost completely
      when cells enter the stationary phase. In vivo depletion of Krr1p leads to
      drastic reduction of 40S ribosomal subunits due to defective 18S rRNA synthesis.
      We propose that Krr1p is required for proper processing of pre-rRNA and the
      assembly of preribosomal 40S subunits.

PMID- 11996122
TI  - Use of blood parameters in fish to assess acidic stress and chloride pollution in
      French running waters.
AB  - The study investigated whether plasmatic parameters in fish such as Cl- content
      could serve as physiological indicators to evaluate water quality. The variations
      of plasma Cl- content in two fish species caught in a wide range of rivers
      representative of the hydrographic system of Lorraine (N-E France) were
      investigated. First, we studied autochthonous populations of chub (Leuciscus
      cephalus) which is a widespread species in the rivers of Lorraine. Organisms
      living in highly mineralised rivers (>1500 microScm(-1))--either naturally or due
      to salt mine contamination--showed plasma Cl- content significantly greater than
      organisms living in river with a lower mineralisation. Second, we investigated
      plasma Cl- content of brown trout (Salmo trutta fario) in poorly mineralised
      streams (<80 microS cm(-1)) with different degrees of acidification, both on
      autochthonous and transferred organisms. While indigenous trout maintained their
      Cl- content even in the acidic streams, transferred trout exhibited an important
      decrease of Cl- content after 48 h of exposure under acidic conditions.

PMID- 11996123
TI  - The relationship between metal concentrations and phenotypes in the Baltic clam
      Macoma balthica (L.) from the Gulf of Gdansk, southern Baltic.
AB  - Soft tissue accumulated concentrations of nine metals (V, As, Se, Ag, Cd, Pb, Mn,
      Cu and Zn) were studied in two main phenotypes (1) according to external shell
      colour (white and pink), and (2) according to shell shape (shell with a rounded
      posterior end--"regular" and with an elongate posterior end and a notable flexure
      -"irregular") of the Baltic clam Macoma balthica from southern Baltic Sea off
      Poland. No differences in metal concentrations were observed between colour-based
      phenotypes. By contrast, "irregular" clams exhibited generally higher
      concentrations of all elements in their tissues than "regular" bivalves. This
      finding provides the first reference on a potential linkage of shell deformation
      with tissue metal concentrations within one entire population of clams living in
      the same habitat. Different ability of metal handling in the shape-based
      phenotypes is presumably related to different physiological capacity of the
      bivalves induced by the selection effect of specific environmental conditions. It
      is suggested that unfavourable conditions in deep waters of the Gulf of Gdansk
      (e.g. hypoxia/anoxia, hydrogen sulphide, elevated bioavailability of metals)
      induces, in a certain part of the population, morphological deformation of shell
      (thereby leading to irregular shape) and in parallel physiological adaptations
      which result in greater sensitivity to trace metals of "irregular" clams. This
      hypothesis however, requires further investigation with special focus on genetic
      divergences between phenotypes because till now we cannot exclude the co
      occurrence of two types (semi-species) of clams in the Gulf: an Atlantic type and
      a Baltic type. Genetic analysis with a use of DALP technique revealed strong
      intrapopulational polymorphism but no fingerprints or intraspecific polymorphism
      characterising any of the phenotypes considered (both colour- and shape-based).
      Since eight polymorphic loci were clearly identified further studies of
      population genetic structure hold optimistic promise.

PMID- 11996124
TI  - Impaired glutathione redox status is associated with decreased survival in two
      organophosphate-poisoned marine bivalves.
AB  - Biomonitoring organophosphate (OP) exposure in marine environments is generally
      achieved by the measurement of acetylcholinesterase activity in bivalves like
      mussels. However, there is evidence that indicates that oxidative stress may be
      implied in OP toxicity. The aim of this study was to evaluate the relationship
      between survival from the OP insecticide fenitrothion and glutathione levels in
      marine bivalves. Mussels (Mytilus galloprovincialis Lam.) and scallops
      (Flexopecten flexuosus Poli) were exposed, in a time to death test, to their LC85
      of fenitrothion for 96 h. OP-poisoned mussels showed reduced (GSH) and oxidised
      (GSSG) glutathione depletion in the digestive gland, muscle and gills. Pectinid
      spats exposed to this insecticide presented GSH depletion in the digestive gland
      and mantle, and a reduction of the GSH/GSSG ratio in gills and mantle. Although
      survival curves were significantly different and mussels withstood twice as much
      fenitrothion as pectinid spats, muscular GSH/GSSG ratio was highly related to
      mortality in both species. We suggest that an impairment in the glutathione redox
      status could result in an induction of the cell death, either by apoptosis or
      necrosis, leading ultimately to the death of the organism. We conclude that
      whereas glutathione depletion can be used as a biomarker of exposure, the
      muscular GSH/GSSG ratio might be used as a biochemical marker of effect and
      individual susceptibility to mortality of marine bivalves exposed to fenitrothion
      or other pollutants that induce oxidative stress.

PMID- 11996125
TI  - Measured variation in boron loads reaching European sewage treatment works.
AB  - Per capita boron loads reaching 48 sewage treatment works (STWs) in The
      Netherlands, Germany, Italy, and the UK have been determined from monitoring
      data. These have been compared with the per capita input predicted from boron in
      detergents, as determined from detergent product sales data. The resulting
      distribution of the ratios of measured boron to boron predicted from consumer
      usage has a 90th percentile of less than 1.5. Boron has previously been shown to
      be a good marker for substances contained in detergent products, as it cannot be
      biodegraded and is not substantially adsorbed in the sewer, and there is little
      or no removal during sewage treatment processes. The monitoring information on
      the distribution of boron loads found at the different STWs should thus be
      indicative of the distribution of other substances released to the environment by
      detergent products, as specified by the relevant industrial category (IC 5
      personal/domestic) in the Technical Guidance Documents. Variation in detergent
      product consumption figures from 18 European countries is also low, with the
      country with the highest per capita detergent consumption having only 1.3 times
      the European average detergent use. Thus the present practice of determining a
      "reasonable worst case" by multiplying the average per capita consumption by a
      factor of four to account for geographic differences in distribution, is
      considered to be inappropriate. This should be replaced by a factor of less than
      two, which combines within country and between country variations to provide a
      reasonable worst case approximation of the load reaching the sewage treatment
      facility.

PMID- 11996126
TI  - Human health risk assessment case study: an abandoned metal smelter site in
      Poland.
AB  - United States Environmental Protection Agency methodologies for human health risk
      assessment (HRA) were applied in a Brownfields Demonstration Project on the
      Warynski smelter site (WSS), an abandoned industrial site at Piekary Slaskie
      town, Upper Silesia, Poland. The HRA included the baseline risk assessment (BRA)
      and the development of risk-based preliminary remedial goals (RBPRGs). The HRA
      focused on surface area covered with waste materials, which were evaluated with
      regard to the potential risks they may pose to humans. Cadmium, copper, iron,
      manganese, lead, and zinc were proposed as the contaminants of potential concern
      (COPCs) at WSS based on archive data on chemical composition of waste located on
      WSS. For the defined future land use patterns, the industrial (I) and
      recreational (II) exposure scenarios were assumed and evaluated. The combined
      hazard index for all COPCs was 3.1E+00 for Scenario I and 3.2E+00 for Scenario
      II. Regarding potential carcinogenic risks associated with the inhalation route,
      only cadmium was a contributor, with risks of 1.6E-06 and 2.6E-07 for Scenario I
      and Scenario II, respectively. The results of the BRA indicated that the
      potential health risks at WSS were mainly associated with waste material exposure
      to cadmium (industrial and recreational scenarios) and lead (industrial
      scenario). RBPRGs calculated under the industrial scenario were 1.17E+03 and
      1.62E+03 mg/kg for cadmium and lead, respectively. The RBPRG for cadmium was
      1.18E+03 mg/kg under the recreational scenario. The BRA results, as well as RBCs,
      are comparable for both scenarios, so it is impossible to prioritize land use
      patterns for WSS based on these results. For choosing a future land use pattern
      or an appropriate redevelopment option, different factors would be decisive in
      the decision-making process, e.g., social, market needs, technical feasibility
      and costs of redevelopment actions or acceptance of local community.

PMID- 11996127
TI  - The importance of the short-term leaching dynamics of wood preservatives.
AB  - The potential environmental impacts from the use of treated timber in aquatic
      areas is under scrutiny as a result of environmental legislation and reports of
      the deleterious environmental effects around treated structures. In this study
      leaching experiments of up to 3 weeks duration were conducted on two species of
      chromated copper arsenate treated timber, dried for different periods of time.
      Increased drying time significantly reduced leaching of Cr and As. The addition
      of a synthetic humic acid increased leaching of Cu and As, but reduced leaching
      of Cr. Putative risk assessments conducted using short-term copper leaching data
      suggested protocol design may influence decisions made regarding the
      environmental acceptability of such preservatives.

PMID- 11996128
TI  - Toxicity of methyl tert-butyl ether to marine organisms: ambient water quality
      criteria calculation.
AB  - In response to increasing concerns over the detection of methyl tert-butyl ether
      (MTBE) in groundwater and surface water and its potential effects in aquatic
      ecosystems, industry and the United States Environmental Protection Agency
      (USEPA) began to collaborate in 1997 to develop aquatic toxicity databases
      sufficient to derive ambient water quality criteria for MTBE consistent with
      USEPA requirements. Acute toxicity data for seven marine species, chronic
      toxicity data for an invertebrate, and plant toxicity data were developed to
      complete the saltwater database. The species tested were Cyprinodon variegatus,
      Gasterosteus aculeatus, Callinectes sapidus, Mytilus galloprovincialis,
      Palaemonetes pugio, Rhepoxynius abronius, Americamysis bahia, and Skeletonema
      costatum. The toxicity tests were conducted in accordance with USEPA and American
      Society for Testing and Materials testing procedures and Good Laboratory Practice
      guidelines. Data developed from this study were consistent with existing data and
      showed that MTBE has low acute and chronic toxicity to the marine species tested.
      Based upon measured MTBE concentrations, acute effects were found to range from
      166 mg MTBE/l for the grass shrimp to 1950 mg MTBE/l for marine mussel. The no
      observed effect concentration for the reproduction and growth of mysids was 26 mg
      MTBE/l during the life cycle test. The toxicity of MTBE to saltwater organisms is
      comparable to its toxicity to the freshwater species tested. Reported MTBE
      concentrations in coastal waters are several orders of magnitude lower than
      concentrations observed to cause effects in marine organisms.

PMID- 11996129
TI  - A comparison of five rapid direct toxicity assessment methods to determine
      toxicity of pollutants to activated sludge.
AB  - Five rapid direct toxicity assessment methods were used in three European partner
      countries to determine the toxicity of single toxicants, mixed toxicants and real
      industrial wastes. The final aim was to protect microbial degradation of organic
      wastes in biological treatment processes and hence enhance the quality of treated
      effluents to be discharged to the environment. Nitrification inhibition,
      Respirometry, Adenosine triphosphate luminescence and Enzyme inhibition were
      tested utilising activated sludge as the testing matrix. The Vibrio fischeri
      toxicity test was used as a surrogate to compare the various microbial bioassays.
      The IC50 (toxicant concentration eliciting a 50% inhibitory effect) was
      determined for a number of pollutants including single toxicants Cd, Cr, Cu, Zn,
      3,5-dichlorophenol, toluene and linear alkylbenzenesulphonate (LAS); a standard
      mixture of metals and LAS; a standard mixture of organics and LAS, and 16
      industrial effluents. The V. fischeri bioassay was also chosen in order to assess
      quality control of toxicant preparation during testing in the different
      laboratories of the partner countries. Comparisons of sensitivity, cost of
      implementation, cost per test, relevance, and ease of use were made. The most
      sensitive bioassays were V. fischeri and Nitrification inhibition, however, this
      depended in the main on the pollutant and mixtures tested. It is recommended that
      during assessment of wastewater toxicity a suite of tests be used rather than
      reliance on one particular test.

PMID- 11996130
TI  - The comparison of rapid bioassays for the assessment of urban groundwater
      quality.
AB  - Groundwater is a complex mixture of chemicals that is naturally variable. Current
      legislation in the UK requires that groundwater quality and the degree of
      contamination are assessed using chemical methods. Such methods do not consider
      the synergistic or antagonistic interactions that may affect the bioavailability
      and toxicity of pollutants in the environment. Bioassays are a method for
      assessing the toxic impact of whole groundwater samples on the environment. Three
      rapid bioassays, Eclox, Microtox and ToxAlert, and a Daphnia magna 48-h
      immobilisation test were used to assess groundwater quality from sites with a
      wide range of historical uses. Eclox responses indicated that the test was very
      sensitive to changes in groundwater chemistry; 77% of the results had a
      percentage inhibition greater than 90%. ToxAlert, although suitable for
      monitoring changes in water quality under laboratory conditions, produced highly
      variable results due to fluctuations in temperature and the chemical composition
      of the samples. Microtox produced replicable results that correlated with those
      from D. magna tests.

PMID- 11996131
TI  - The contribution of 2,3,5-trichlorophenyl methyl sulfone, a metabolite of 1,2,4
      trichlorobenzene, to the delta-aminolevulinic acid synthetase induction by 1,2,4
      trichlorobenzene in rat liver.
AB  - In the present study, we investigated the contribution of methylsulfonyl
      metabolite derived from 1,2,4-trichlorobenzene (1,2,4-TCB) on the delta
      aminolevulinic acid (ALA) synthetase induction by the parent compound in rats.
      The time courses of increasing of hepatic microsomal total cytochrome P450
      content after a single i.p. administration of 1,2,4-TCB (1.36 mmol/kg), and 2,3,5
      and 2,4,5-trichlorophenyl methyl sulfones (2,3,5- and 2,4,5-TCPSO2Mes) (50
      micromol/kg each) were in parallel with those of increasing of the total heme
      content in liver microsomes. 1,2,4-TCB significantly increased the heme oxygenase
      activity, but 2,3,5- and 2,4,5-TCPSO2Mes did not. On the other hand, 1,2,4-TCB
      and 2,3,5-TCPSO2Me markedly enhanced the ALA synthetase activity. No change was
      observed in this enzyme activity after the administration of 2,4,5-TCPSO2Me.
      After the administration of 1,2,4-TCB to the rats treated with DL-buthionine
      (S,R)-sulfoximine (BSO) and to the non-BSO-treated rats, the concentrations of
      both 2,3,5- and 2,4,5-TCPSO2Mes were significantly lower in liver of the BSO
      treated rats than in liver of the non-BSO-treated rats. Additionally, the 1,2,4
      TCB did not elevate the ALA synthetase activity in the BSO-treated rats. On the
      other hand, the administration of 2,3,5-TCPSO2Me to BSO-treated rats resulted in
      induction of ALA synthetase. The results strongly suggest that the methyl sulfone
      derived from 1,2,4-TCB, i.e., 2,3,5-TCPSO2Me, contributes highly to the induction
      of the ALA synthetase activity by the parent compound.

PMID- 11996132
TI  - Effects of waterborne exposure to 4-nonylphenol on plasma sex steroid and
      vitellogenin concentrations in sexually mature male carp (Cyprinus carpio).
AB  - 4-Nonylphenol (NP) has been shown to elicit estrogenic responses both in vivo and
      in vitro. The mechanism by which NP exerts estrogenic and other endocrine
      modulating effects in vivo remains unclear, however. The goal of this study was
      to evaluate the ability of NP to elicit estrogenic responses through indirect
      mechanisms of action involving the modulation of endogenous steroid hormone
      concentrations. Sexually mature male common carp (Cyprinus carpio) were exposed
      to aqueous NP concentrations ranging from <0.05 to 5.4 microg NP/l for 28-31 d.
      Approximately 0.5-3.5 ppm of NP was detected in pooled plasma samples or tissue
      samples from the carp studied. NP exposure did not significantly increase plasma
      concentrations of 17beta-estradiol (E2), testosterone (T) or vitellogenin (VTG).
      Excluding outliers, plasma E2 concentrations ranged from <175 to 700 pg E2/ml. T
      concentrations ranged from 940 to 24,700 pg T/ml plasma. The greatest VTG
      concentration detected was 52 microg/ml. One-third of the plasma samples tested
      contained <1 microg VTG/ml. Overall, the results of this study did not support
      the hypothesis that exposure to waterborne NP can modulate concentrations of
      steroid hormones in the plasma of sexually mature male carp. The results did,
      however, raise a number of questions regarding the utility of estradiol
      equivalent (EEQ) estimates as a means of predicting in vivo effects of estrogenic
      substances. Furthermore, they provide information regarding the concentrations
      and variability of E2, T, and VTG in the plasma of sexually mature male carp,
      which may aid in design and interpretation of future studies.

PMID- 11996133
TI  - Effects of cadmium upon longevity of Diplostomum sp. (Trematoda: Diplostomidae)
      cercariae.
AB  - Laboratory experiments were conducted to examine the impact of cadmium (Cd) on
      survival of Diplostomum sp. cercariae. Freshly emerged cercariae were exposed to
      Cd solutions at concentrations ranging between 0.2 and 200 microg/l. The
      mortality patterns and mean survival times (MSTs) of the exposed parasites were
      determined by the Kaplan-Meier estimator and were compared (Log-Rank test) to
      corresponding patterns and estimators of the unexposed controls. Cd
      concentrations >20 microg/l caused statistically significant changes in the
      mortality pattern of Diplostomum sp. cercariae and reduced MST by at least five
      hours compared to the control group, where MST was 52 h. The results show that
      longevity of the free-living Diplostomum sp. cercariae can be reduced by direct
      exposure to heavy metals. Cd contamination of aquatic habitats thus potentially
      can have an impact on parasite populations and communities.

PMID- 11996134
TI  - Short-term responses of Oryzias latipes (Pisces: Adrianichthyidae) and
      Macrobrachium nipponense (Crustacea: Palaemonidae) to municipal and
      pharmaceutical waste water in Beijing, China: survival, behaviour, biochemical
      biomarkers.
AB  - Whole effluent toxicity was assessed for the fish Oryzias latipes and the prawn
      Macrobrachium nipponense for 18 h in a dilution series (0-66%) of the inflow and
      effluent of a municipal waste water treatment plant as well as waste water from a
      teramycin producing pharmaceutical industry, before, during and after a pilot
      laboratory purification process. The waste waters caused acute toxicity as
      measured by inhibition of light emission in the luminiscent bacterium Vibrio
      qingaiensis sp. nov. (Q67). EROD and aryl hydrocarbon hydroxylase activity in in
      vitro carp liver-cells showed a dose-dependent toxic response to the municipal
      waste water. Behavioural responses and time-to-death of fish and prawn, recorded
      online with the "Multispecies Freshwater Biomonitor" proved to be concentration-
      and time-dependent sensitive toxicity indicators in both types of waste water.
      Behaviour changed stepwise from normal activity to (increased or decreased)
      activity to more time spent on ventilation and finally to increased morbidity at
      higher concentration and time of exposure. The municipal waste water treatment
      plant managed to reduce toxicity to bacteria (Q67), prawn and fish. The
      pharmaceutical waste water treatment process still has to be improved, in order
      to reduce toxicity for fish and prawn.

PMID- 11996135
TI  - Efficacy of vitamin-C (L-ascorbic acid) in reducing genotoxicity in fish
      (Oreochromis mossambicus) induced by ethyl methane sulphonate.
AB  - The genotoxic effects of ethyl methane sulphonate (EMS) have been assessed in a
      fish, Oreochromis mossambicus with endpoints including chromosome aberrations,
      abnormal red blood cell nuclei, abnormal sperm morphology, and protein content
      (both qualitative and quantitative) of selected tissues, namely, muscle, heart,
      eye, brain, gill, liver, spleen and kidney. EMS caused chromosomal aberrations,
      nuclear anomalies in red blood cells, abnormal sperm morphology, and alteration
      of protein synthesis in various tissues. Some of the EMS toxicity appeared to be
      modulated and ameliorated in this fish by vitamin-C treatment.

PMID- 11996136
TI  - Chromosomal damage in peripheral blood lymphocytes of traffic policemen and taxi
      drivers exposed to urban air pollution.
AB  - Urban air contains a diversity of chemical compounds, some of which are
      genotoxins. An increased risk of cancer has also been reported in occupations
      with heavy exposure to traffic-related pollution. The aim of this study was to
      assess the cytogenetic effects of urban air pollution by analyzing the
      chromosomal aberration (CA) frequencies in lymphocytes and to estimate the
      polycyclic aromatic hydrocarbons (PAHs) exposure by measuring urinary 1
      hydroxypyrene (1-OHP) levels. A total of 15 traffic policemen and 17 taxi drivers
      working in the city of Ankara were the exposed groups and 23 healthy men working
      in the office departments were the control group. The overall mean +/- S.D.
      values of 1-OHP excretions of traffic policemen, taxi drivers and control
      subjects were 0.59 +/- 0.40 micromol/mol creatinine, 0.32 +/- 0.25 micromol/mol
      creatinine and 0.57 +/- 0.36 micromol/mol creatinine, respectively. Urinary 1-OHP
      levels of non-smoking policemen were significantly greater than those of
      nonsmoking control subjects (p < 0.05). The overall mean +/- S.D. values for CA
      frequencies (%) from policemen, taxi drivers and control group were 1.29 +/-
      1.59, 1.81 +/- 1.79, and 0.26 +/- 0.73, respectively. There was a significantly
      greater frequency of CAs in exposed groups relative to the matched control
      population (p < 0.05; p < 0.01). Age, sex and smoking habits have not influenced
      the cytogenetic end-point in this study. Our results demonstrate that
      occupational exposure to urban air pollutants leads to a significant induction of
      cytogenetic damage in peripheral lymphocytes of traffic policemen and taxi
      drivers.

PMID- 11996137
TI  - Acute toxicity of chlorophenols to earthworms using a simple paper contact method
      and comparison with toxicities to fresh water organisms.
AB  - An acute toxicity test of chlorophenols on earthworms (Eisenia fetida) was
      performed using a simple paper contact method proposed by OECD testing guideline
      no. 207, that were applied as an earthworm toxicity test. The median lethal
      concentration, EC50, had significant correlation with logP(ow) (1-octanol/water
      partition coefficient) of the chemicals. The toxicity of chlorophenols on E.
      fetida was compared with toxicities for other species: an algae (Selenostrum
      capricornutum), a crustacean (Daphnia magna), and a fish (Oryzias latipes). It
      was found that the toxicity of chlorophenols was almost same for E. fetida and
      for fresh water organisms. These results suggest the possibility of drawing
      correlations between the effects of pollutants on living things in different
      environments, fresh water and soil.

PMID- 11996138
TI  - Effect of 17beta-estradiol on the reproduction of Japanese medaka (Oryzias
      latipes).
AB  - Estrogenic compounds such as 17beta-estradiol (E2) and its analogs are present in
      the aquatic environment and can adversely affect the reproductive systems of
      aquatic organisms. Although E2 has been detected at a maximum concentration of 64
      ng/l in effluents of sewage treatment works (STWs), few reports address the
      associated effects on reproduction in fish. Therefore, we exposed adult medaka
      (Oryzias latipes) to mean measured E2 concentrations of 29.3, 55.7, 116, 227, and
      463 ng/l for 21 d and assessed the effects on the egg number and fertility of
      paired medaka during the exposure period. In addition, we determined the hepatic
      vitellogenin (Vtg) concentration and histologically assessed the gonads of these
      fish. The number of egg produced and fertility of the paired medaka exposed to
      463 ng/l E2 were significantly less compared with those of the control fish.
      Males in all treatment groups had developed testis-ova. Males treated with E2
      concentrations = 55.7 ng/l contained relating great concentrations of hepatic
      Vtg. Therefore, although only the greatest E2 concentration tested in our study
      affected fecundity and fertility, effects of E2 were observed on induction of Vtg
      and testis-ova in male medaka exposed to environmentally relevant concentrations
      of E2.

PMID- 11996139
TI  - Genotoxicological effects of some phenoxyherbicides and their metabolites on
      Bacillus subtilis M45 Rec- and H17 Rec+ strains.
AB  - Because they are used in a number of commercial preparations phenoxyacetic acids
      and their salts can occur in wastewater. During their degradation genotoxic
      substances may be created. The results of investigations of biodegradability and
      genotoxicity of some phenoxyherbicides are presented. Commercial formulations of
      2,4-D (Aminopielik 720) and MCPA (Chwastox Extra) were the substrates studied.
      Biodegradation tests were conducted according to OECD guidelines for testing of
      chemicals--confirmatory test (OECD Method 303 A). Genotoxicity tests were
      conducted with Bacillus subtilis strains according to the method of [Chemical
      Mutagens, vol. 6, Plenum Press. New York, 1980, p. 149]. Genotoxicity of
      biodegradation products was also studied. Both commercial formulations were
      biodegradable. Aminopielik 720 was potentially genotoxic but only at great
      concentrations while Chwastox Extra was not genotoxic. Biodegradation products of
      neither compound were genotoxic.

PMID- 11996140
TI  - Effects of aluminum on physiological metabolism and antioxidant system of wheat
      (Triticum aestivum L.).
AB  - The Al-tolerant cultivar TAM202 and the Al-sensitive cultivar TAM 105 of winter
      wheat (Triticum aestivum L.) were exposed to 0, 50, 75, 100 or 150 microM of Al.
      The absorption of Al by wheat, the growth of root, several key enzymes concerned
      with C, N and P metabolism, as well as key constituents of antioxidant system,
      were investigated. The results showed that TAM105 absorbed more Al than TAM202
      and its root growth (presented by the length) was inhibited more severely. The
      root growth was most closely related to mononuclear Al (Ala) activity. The
      metabolic enzymes (presented by glucose-6-phosphate dehydrogenase, nitrate
      reductase and acid phosphatase) in TAM202 were Al-tolerant. Presented by
      superoxide dimutase (SOD) and the content of reduced glutathione (GSH) and
      malondialdehyde (MDA), antioxidant system in TAM202 indicated lower oxidative
      stress and greater ability to protect the cultivar.

PMID- 11996141
TI  - Changes in mutagenicity during biodegradation of fenitrothion.
AB  - In order to investigate changes in the mutagenicity of fenitrothion during its
      biodegradation in solution, measurements were conducted at intervals in batch
      cultures incubated under anaerobic or aerobic conditions. Fenitrothion-degrading
      bacteria were obtained from a green onion field on the west side of Gifu
      University, Japan. Fenitrothion was almost completely decomposed by day 12 under
      both types of incubation condition. The indirect mutagenicity of the solution to
      strains YG1029 and YG1042, however, increased markedly during anaerobic
      biodegradation. The increase in mutagenicity was partially due to amino
      fenitrothion, a metabolite formed during anaerobic biodegradation of
      fenitrothion.

PMID- 11996142
TI  - Regression comparisons of Tetrahymena pyriformis and Poecilia reticulata
      toxicity.
AB  - The toxicity data of chemicals common to both the Poecilia reticulata mortality
      assay and the Tetrahymena pyriformis growth impairment assay were evaluated. Two
      chemicals were not toxic at saturation in the T. pyriformis assay. In addition,
      due to abiotic transformation, a third chemical was removed from further
      consideration. Each chemical was a priori assigned a mode of toxic action:
      neutral non-covalent, polar non-covalent, or electrophilic covalent toxicity. To
      further investigate comparisons between endpoints, polar and electrophilic
      chemicals were separated into class-based groups. The polar non-covalent
      chemicals were separated into phenols and anilines, while the electrophilic
      chemicals were separated into those reacting via Schiff-base formation (i.e.,
      aldehydes) and those reacting via bimolecular substitution to a nucleophile
      (i.e., selected nitroaromatics). A comparison of toxic potency as a collective
      set was statistically described by the relationship; log(LC50(-1)) =
      1.05(log(IGC50(-1))) + 0.56, n = 124; r2 = 0.85; s = 0.42; F = 682; Pr > F =
      0.0001. The relationship between endpoints was inversely proportional to
      reactivity associated with the mode of action. While the comparative toxicity for
      neutral narcotics exhibited an excellent fit (r2 = 0.94), the fits for polar
      narcotics and electrophiles were poorer, r2 = 0.69 and 0.62, respectively.
      Investigations into class-based groupings indicated fit of toxic potency data for
      aldehydes (r2 = 0.85) and phenols (r2 = 0.81) were quite good. However, fits for
      anilines (r2 = 0.43) and nitroaromatics (r2 = 0.68) revealed that toxicity was
      not as well related between endpoints for these chemicals.

PMID- 11996143
TI  - New large solar photocatalytic plant: set-up and preliminary results.
AB  - A European industrial consortium called SOLARDETOX has been created as the result
      of an EC-DGXII BRITE-EURAM-III-financed project on solar photocatalytic
      detoxification of water. The project objective was to develop a simple, efficient
      and commercially competitive water-treatment technology, based on compound
      parabolic collectors (CPCs) solar collectors and TiO2 photocatalysis, to make
      possible easy design and installation. The design, set-up and preliminary results
      of the main project deliverable, the first European industrial solar
      detoxification treatment plant, is presented. This plant has been designed for
      the batch treatment of 2 m3 of water with a 100 m2 collector-aperture area and
      aqueous aerated suspensions of polycrystalline TiO2 irradiated by sunlight. Fully
      automatic control reduces operation and maintenance manpower. Plant behaviour has
      been compared (using dichloroacetic acid and cyanide at 50 mg l(-1) initial
      concentration as model compounds) with the small CPC pilot plants installed at
      the Plataforma Solar de Almeria several years ago. The first results with high
      content cyanide (1 g l(-1)) waste water are presented and plant treatment
      capacity is calculated.

PMID- 11996144
TI  - Aniline degradation by Electro-Fenton and peroxi-coagulation processes using a
      flow reactor for wastewater treatment.
AB  - The degradation of 10-30 l of a 1000 ppm aniline solution in 0.050 M Na2SO4 +
      H2SO4 at pH 3.0 and 40 degrees C by Electro-Fenton and peroxi-coagulation
      processes at constant current until 20 A has been studied using a pilot flow
      reactor in recirculation mode with a filter-press cell containing an anode and an
      oxygen diffusion cathode, both of 100 cm2 area. H2O2 is produced by the two
      electron reduction of O2 at the cathode, being accumulated with a current
      efficiency between 60% and 80% at the first stages of electrolyses performed with
      a Ti/Pt anode. In the presence of 1 mM Fe2+, less H2O2 is accumulated, but it is
      not detected using an Fe anode. The Electro-Fenton process with 1 mM Fe2+ and a
      Ti/Pt or DSA anode yields an insoluble violet polymer, while the soluble total
      organic carbon (TOC) is gradually removed, reaching 61% degradation after 2 h at
      20 A. In this treatment, pollutants are preferentially oxidized by hydroxyl
      radicals formed in solution from reaction of Fe2+ with H2O2. The peroxi
      coagulation process with an Fe anode has higher degradation power, allowing to
      remove more than 95% of pollutants at 20 A, since some intermediates coagulate
      with the Fe(OH)3 precipitate formed. Both advanced electrochemical oxidation
      processes (AEOPs) show moderate energy costs, which increase with increasing
      electrolysis time and applied current.

PMID- 11996145
TI  - Biosorption of cadmium and copper contaminated water by Scenedesmus abundans.
AB  - Experiments were conducted comparing the individual removals of cadmium and
      copper from water via biosorption using Scenedesmus abundans, a common green
      algae, to removal in a multi-component system to determine competitive effects,
      if any, between the metals. The goal was to characterize the biological treatment
      of water contaminated with heavy metals using live aquatic species. In addition,
      experiments were performed to measure cell viability as a function of metal
      concentration and also to compare metal removal using living species to that
      using nonliving ones. It was shown that, while both living and nonliving S.
      abundans removed cadmium and copper from water, living algae significantly
      outperformed nonliving algae. Further, in characterizing biosorption by three
      concentrations of live S. abundans, capacity curves were created comparing the
      metal biosorbed per mass algae to the initial metal concentration in solution.
      The algae concentration was not a factor in the biosorption of either metal
      individually, such that the capacity of the algae for the metal increased with
      decreasing algae concentration. At the lowest algae concentration considered,
      competitive effects were observed at copper and cadmium concentrations above 4
      mg/l each. At the highest algae concentration considered, no competitive effects
      were observed in the range of cadmium and copper concentrations studied (1-7
      mg/l). It was concluded that biological treatment of heavy metal contaminated
      water is possible and that at adequately high algae concentrations, multi
      component metal systems can be remediated to the same level as individual metals.

PMID- 11996146
TI  - The surface characteristics of activated carbon as affected by ozone and alkaline
      treatment.
AB  - The surface chemical characteristics of activated carbon treated by ozone and
      alkaline are determined in terms of surface functional groups and surface
      acidity. Surface functional groups are analyzed by the IR spectroscopic method
      and Boehm's titration technique. The surface acidity of activated carbon is
      determined by electrophoretic mobility measurements. The oxygen concentration of
      activated carbon increases upon ozone and NaOH treatment. Surface functional
      groups increase mostly in the hydroxyl and carboxyl categories rather than the
      carbonyl category upon ozone and NaOH treatment.

PMID- 11996147
TI  - Ozonation of activated carbon and its effects on the adsorption of VOCs
      exemplified by methylethylketone and benzene.
AB  - Ozonation can modify the surface property of an activated carbon such as specific
      surface area, pore volume, and functional group. Results indicate that ozonation
      can increase the specific surface area of an activated carbon from 783+/-51 to
      851+/-25 m2/g due in part to increasing micropores (those below 15 A). However,
      there is no change in macropore and mesopore upon ozonation. The amount of oxygen
      functional group (OFG) increases from 197+/-4 to 240+/-4 microeq/g, mostly in
      hydroxyl and carboxyl groups upon ozone treatment. These oxygen-containing
      functional groups are stable in the temperature range 30-250 degrees C, but begin
      to decompose when temperature increases beyond 300 and 350 degrees C. When the
      temperature reaches 1200 degrees C, all OFGs virtually disappear. The effect of
      ozone treatment on the adsorption of volatile organic carbon (VOC) was
      exemplified by methylethylketone (MEK) and benzene. The adsorption density of MEK
      and benzene by ozone treated activated carbon (AC(O3)) are greater than that by
      the untreated (AC), with MEK being more adsorbable than benzene. Results of
      factorial analysis indicate that physical characteristics, namely, micropore, BET
      surface area, pore diameter (PD), micropore volume (MV) play an important role on
      benzene and MEK adsorption.

PMID- 11996148
TI  - Treatment of solutions with binary solutes using an admicellar enhanced CSTR:
      background solute effect.
AB  - This study presents an admicellar enhanced continuous-flow stirred tank reactor
      (CSTR). Solutions containing single and binary aliphatic alcohols are introduced
      into this reactor for breakthrough experiments. Two phenomena occur during
      experiments with binary solutes: (a) a competitive effect caused by background
      solutes with relatively high hydrophobicity; (b) a co-solvent effect attributable
      to background solutes with relatively low hydrophobicity. The competition
      phenomenon and the corresponding mechanism involved are well demonstrated by
      directly monitoring the pre-adsolubilized solutes drawn out back to the solution
      while adsolubilizing other solutes with higher hydrophobicity. On the other hand,
      adsolubilization kinetics hindered by the background solute, which acts as a co
      solvent, significantly alters the slopes of breakthrough curves of the target
      solute treated in the reactor.

PMID- 11996149
TI  - Modeling competitive adsorption of molybdate, sulfate, selenate, and selenite
      using a Freundlich-type multi-component isotherm.
AB  - This study examined the interactions of MoO4(2-) + SO4(2-), MoO4(2-) + SeO4(2-),
      and MoO4(2-) + SeO3(2-) systems on gamma-Al2O3 to better understand the
      competitive adsorption of these anions in the natural environment. The Freundlich
      isotherms of anionic adsorption onto gamma-Al2O3 in single and binary solutes
      were also investigated to estimate the competition between these anions.
      Experimental results indicate that a higher concentration of competitive solute
      yields a higher efficiency of the competitive solute's prevention of MoO4(2-)
      adsorption. The most significant result was found in the MoO4(2-) + SeO3(2-)
      system. The Freundlich isotherm constant (n) increases with the competitive
      solute concentration. The suitability of a Freundlich-type isotherm, the
      Sheindorf-Rebuhn-Sheintuch (SRS) equation, and the modified SRS equation in
      representing the competitive adsorption of MoO4(2-), SO4(2-), SeO4(2-), and
      SeO3(2-) on gamma-Al2O3 surface, was also examined. Each set of isotherm data was
      found to conform to linear SRS expressions, allowing competition coefficients to
      be derived on a concentration basis for each binary-solute system. The
      competition coefficient aij and relative affinity coefficients alphaij can be
      seen as a way to quantify competitive interactions. The proposed SRS and modified
      SRS equations are simple mathematical expressions accounting for competitive
      interactions of anions present in a mixture for the range of concentrations over
      which each individual component exhibits Freundlich behavior.

PMID- 11996150
TI  - Oxidation of diethylene glycol with ozone and modified Fenton processes.
AB  - This paper describes a study of oxidation of diethylene glycol (DEG) by ozone and
      modified Fenton process (hydrogen peroxide and ferric salt mixture) in aqueous
      solution. Both oxidation processes were able to oxidize relatively high
      concentrations of DEG effectively. DEG reacted primarily through hydroxyl radical
      produced by decomposition of ozone, and about 3 mol of ozone were consumed per
      mole of DEG removed during the process. For modified Fenton oxidation, stepwise
      addition of hydrogen peroxide (H2O2) and ferric salt (Fe(III)) resulted in much
      higher removal of DEG than one-time pulse addition of the chemicals. The extent
      of DEG removal increased with increasing concentrations of both H2O2 and Fe(III).
      Oxidant consumption per mole of DEG oxidized was one order of magnitude higher
      for hydrogen peroxide than those observed for ozone. Overall, ozonation produced
      higher concentrations of aldehydes, and modified Fenton treatment produced higher
      concentrations of carboxylic acids for the same levels of DEG oxidation. The
      major products of ozonation were glycolaldehyde, glyoxal, formaldehyde,
      acetaldehyde, and acetic, formic, pyruvic, oxalic and glyoxalic acids. The major
      products of modified Fenton oxidation were formaldehyde, and formic and acetic
      acids.

PMID- 11996151
TI  - Influence of surfactants on solubilization and fungal degradation of fluorene.
AB  - Eighteen fungal strains were tested in toxicity assays with surfactants in order
      to select surfactants and strains tolerant to surfactants for degradation assays.
      Two nonionic surfactants were used, an alkylphenol ethoxylate, Triton X-100, a
      sorbitan ester, Tween 80 and an anionic surfactant, sodium dodecyl sulfate.
      Solubilization and biodegradation tests were conducted in liquid medium batch;
      fluorene was quantified by HPLC. Results showed the enhancement of fluorene
      solubilization by the three surfactants, good tolerance of nonionic surfactants
      by the fungal strains and the enhancement of the biodegradation of fluorene by
      Doratomyces stemonitis (46-62%) and Penicillium chrysogenum (28-61%) in the
      presence of Tween 80 (0.324 mM) after 2 days.

PMID- 11996152
TI  - Catalytic oxidation of TNT by activated carbon.
AB  - Activated carbon can remove 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitrobenzene
      (TNB) from aqueous solution and promote oxidation of TNT. After equilibrating a
      0.35 mM TNT solution with activated carbon (0.2-1% w/v), HPLC and GC/MS analysis
      confirmed the presence of 2,4,6-trinitrobenzaldehyde (TNBAld) and 2,4,6
      trinitrobenzene (TNB), and provided strong evidence supporting 2,4,6
      trinitrobenzyl alcohol (TNBAlc) as an intermediate of TNT oxidation. After 6 d,
      TNT and its oxidation products were strongly bound to the activated carbon, while
      TNB was extractable with acetonitrile. Observations indicate that activated
      carbon catalyzes TNT oxidation to TNBAlc, which is readily oxidized to TNBAld and
      TNB in the absence of activated carbon under dark conditions. While adsorbed TNB
      was extractable with acetonitrile, activated carbon promoted rapid TNT oxidation
      and formation of unextractable residues. Strong binding is attributed to
      catalyzed oxidation of the TNT methyl group, probably through a free radical
      mechanism, and subsequent chemisorption of oligomers and polymerized products
      that are not desorbed from micropores. Our observations indicate TNT oxidation
      and bound residue formation after sorption by activated carbon increases the
      effectiveness of activated carbon to decontaminate water.

PMID- 11996153
TI  - Flotation of metal-loaded clay anion exchangers. Part II: the case of arsenates.
AB  - Hydrotalcite-like materials, or otherwise termed layered double hydroxides, are
      clays with an ability to remove anions. As they usually are in powder form, these
      sorbents often present appreciable problems in the solid/liquid separation
      process following the sorption stage. Sorptive flotation of metal-loaded
      particles was investigated in this paper, as an alternative two-stage process. In
      the sorption process, satisfactory removals of arsenic(V) were obtained onto
      synthetic hydrotalcite particles from water. The effect of some parameters, like
      the solution ionic strength, concentrations, temperature, etc. was examined.
      During the second stage of the process, hydrotalcite fine particles were removed
      from the liquid phase by dispersed-air flotation; various surfactants were tested
      in relation to the ionic strength of the solution. The combined process of
      sorptive flotation provides promising results for arsenic removal.

PMID- 11996154
TI  - As(III) removal from groundwaters using fixed-bed upflow bioreactors.
AB  - The application of biological oxidation of iron and manganese, as a potential
      treatment method for the removal of arsenic from contaminated groundwaters, was
      examined in this paper. This method was based on the growth of certain species of
      indigenous bacteria, which are capable of oxidizing the soluble iron and
      manganese ions; the oxidized forms can be subsequently removed from the aqueous
      stream by over 97%, through their transformation to insoluble oxides and
      separation by a suitable filter medium. Arsenic was removed by around 80%, under
      certain conditions, which were found to be sufficient for Fe(II) removal
      (dissolved oxygen 2.7 mg/l, redox 280-290 mV, pH 7.2, U 8.25 m/h). The specific
      treatment technique presents several advantages towards conventional
      physicochemical treatment methods, such as enhanced coagulation or direct
      adsorption since: (a) it does not require the addition of other chemicals for
      oxidizing and removing As(III), (b) it does not require close monitoring of a
      breakthrough point, as in conventional column adsorption processes and (c) it
      could find application for the removal of, at least, three groundwater
      contaminants (Fe, Mn, As).

PMID- 11996155
TI  - Fixed-bed study for lanthanide (La, Eu, Yb) ions removal from aqueous solutions
      by immobilized Pseudomonas aeruginosa: experimental data and modelization.
AB  - A fixed-bed study was carried out by using cells of Pseudomonas aeruginosa
      immobilized in polyacrylamide gel as a biosorbent for the removal of lanthanide
      (La, Eu, Yb) ions from aqueous solutions. The effects of superficial liquid
      velocity based on empty column, particle size, influent concentration and bed
      depth on the lanthanum breakthrough curves were investigated. Immobilized biomass
      effectively removed lanthanum from a 6 mM solution with a maximum adsorption
      capacity of 342 micromolg(-1) (+/-10%) corresponding closely to that observed in
      earlier batch studies with free bacterial cells. The Bohart and Adams sorption
      model was employed to determine characteristic parameters useful for process
      design. Results indicated that the immobilized cells of P. aeruginosa enable
      removal of lanthanum, europium and ytterbium ions from aqueous effluents with
      significant and similar maximum adsorption capacities. Experiments with a mixed
      cation solution showed that the sequence of preferential biosorption was Eu3+ >
      or = Yb3+ > La3+. Around 96+/-4% of the bound lanthanum was desorbed from the
      column and concentrated by eluting with a 0.1 M EDTA solution. The feasibility of
      regenerating and reusing the biomass through three adsorption/desorption cycles
      was suggested. Neural networks were used to model breakthrough curves performed
      in the dynamic process. The ability of this statistical tool to predict the
      breakthrough times was discussed.

PMID- 11996156
TI  - Homogeneous degradation of 1,2,9,10-tetrachlorodecane in aqueous solutions using
      hydrogen peroxide, iron and UV light.
AB  - The homogeneous degradation of the polychlorinated n-alkane, 1,2,9,10
      tetrachlorodecane (T4C10), was studied in aqueous solutions of hydrogen peroxide,
      including Fenton and photo-Fenton reaction conditions. All solutions were
      adjusted to a pH of 2.8 and an ionic strength of 0.1 M NaClO4 prior to
      photolysis. T4C10 (2 x 10(-6) M) was substantially degraded by the H2O2/UV system
      (1.0 x 10(-2) M H2O2), with 60% disappearance in 20 min of irradiation in a
      photoreactor equipped with 300 nm lamps of light intensity 3.6 x 10(-5) Ein L(-1)
      min(-1) (established by ferrioxalate actinometry). The reaction produced
      stoichiometric amounts of chloride ion indicating complete dechlorination of the
      chlorinated n-alkane. T4C10 degraded very slowly under Fenton (Fe2+/H2O2/dark)
      and Fenton-like (Fe3+/H2O2/dark) conditions. However, when the same solutions
      were irradiated, T4C10 degraded more rapidly than in the H2O2/UV system, with 61%
      disappearance in 10 min of exposure. The rapid degradation is related to the
      enhanced degradation of hydrogen peroxide to oxidizing *OH radicals under photo
      Fenton conditions. Degradation was inhibited in both the H2O2/UV and photo-Fenton
      systems by the addition of KI and tert-butyl alcohol due to *OH scavenging.

PMID- 11996157
TI  - Review of the treatment strategies for oral malodour.
AB  - Breath malodour, a significant social and/or psychological handicap, may be
      caused by several intra- and extraoral factors. Malodour of intraoral origin is
      the result of microbial putrefaction, during which volatile sulphur compounds
      (VSC) and other volatile compounds are produced. The treatment of oral malodour
      can therefore be focused on the reduction of the intraoral bacterial load and/or
      the conversion of VSC to nonvolatile substrates. This article outlines the
      efficacy and mechanisms of different antimalodour approaches. Most approaches
      were found to be inefficient and/or short lasting. The most successful treatment
      involves mechanical debridement (including toothbrushing, flossing, and tongue
      cleaning), possibly combined with the use of an antimicrobial mouthrinse.

PMID- 11996158
TI  - Oral findings in patients with primary Sjogren's syndrome and oral lichen planus-
      a preliminary study on the effects of bovine colostrum-containing oral hygiene
      products.
AB  - Bovine colostrum is rich in antimicrobial substances and growth factors. The
      purpose of this open study was to examine and compare the interventory effects of
      daily use of bovine colostrum-containing oral hygiene products (CHP) on oral
      symptoms and findings in 20 patients with primary Sjogren's syndrome (pSS) and 20
      age-matched patients with oral lichen planus (OLP). Objective oral measures and
      self-assessment of oral symptoms and general health were conducted before and
      after 90 days' use of CHP. The pSS patients had more systemic diseases,
      medication intake, oral dryness, poorer general health and lower salivary
      secretion than the OLP patients, who had the highest plaque index (PI) and the
      most mucosal soreness. Oral dryness and soreness were correlated to general
      health. In both patient groups. unstimulated whole saliva flow rate (UWS) had
      increased, PI and periodontal pocket depth (PPD) were reduced, and general health
      and oral dryness and soreness had improved after using CHP. A decrease in hyphae
      was found in candida smears from both groups and in blastospores in OLP smears. A
      reduction in the extension of the mucosal lesions was observed in 15 OLP
      patients. Results suggested beneficial effects of intervention with CHP on oral
      symptoms, general health, UWS, PI, PPD and candidal load in two patient groups-
      pSS and OLP--representing different oral symptomatology.

PMID- 11996159
TI  - Enzymatic markers of salivary cell injury in saliva of type 1 diabetic children.
AB  - To find evidence of salivary gland involvement in human type I diabetes, we
      explored the changes in aminotransferase and lactate dehydrogenase activities, as
      indices of cellular injury, in the whole saliva of diabetic children. Although no
      significant difference in these enzymatic activities was observed between control
      and diabetic children as a whole, a negative correlation was found between
      enzymatic activities and duration of the disease, the highest values being
      detected in the diabetic subgroup diagnosed for less than 4 years. This suggests
      that some cell damage could be present in salivary glands of recently diagnosed
      diabetic children, likely as a result of immune-mediated alterations. In
      conclusion, these results may support the hypothesis that, as in rodents, the
      salivary glands could be an additional target of the immunological attack mainly
      directed against pancreatic beta-cells and resulting in type 1 diabetes.

PMID- 11996160
TI  - Effectiveness of metronidazole gel on cyclosporine-induced gingival overgrowth in
      heart transplant patients.
AB  - To evaluate the efficacy of metronidazole on cyclosporine-induced gingival
      overgrowth (GO), a prospective intra-subject double-blind longitudinal study was
      performed on six heart transplant patients with GO. All patients underwent
      scaling and root planing before any treatment. Metronidazole gel (Elyzol, Cabon)
      was then applied in two of the four anterior hemi-sextants of each subject,
      following a balanced random pre-programmed list, with a placebo gel being applied
      to the remaining two hemi-sextants. Plaque index (PI), bleeding on probing (BP)
      and probing depth (PD) were recorded for all teeth of the four anterior hemi
      sextants before and at 1, 2, 3, and 4 months after gel application. A general
      linear model was fitted and ANOVA for repeated measurements with split-plot
      design and Chi-square analysis were used for statistical analysis. PD
      significantly decreased after 1 month following both treatments. Analogous
      results were obtained as regards PI and BP. No statistically significant
      difference was detected between results obtained with metronidazole and placebo.
      However, PD in the group of teeth treated with placebo significantly increased
      after 4 months, while PD values obtained from teeth treated with metronidazole
      remained statistically unchanged with respect to the 1st month. In conclusion,
      short-term results suggest that metronidazole and placebo are equally effective
      in reducing periodontal parameters and GO when associated with scaling and root
      planing. Long-term results, however, showed greater efficacy of metronidazole
      with respect to placebo in controlling cyclosporine-induced GO.

PMID- 11996161
TI  - Statistical modeling of tooth mobility after treating adult periodontitis.
AB  - The healing process following periodontal surgery for advanced adult
      periodontitis is described. Of the various indicators, tooth mobility (TM) is
      considered, and its relation to surgical treatment and the time lapse from the
      flap surgery is quantitatively modeled by non-parametric regression. Mobility is
      measured by an electronic apparatus, which also automatically performs the
      modeling. A new statistical method for TM prediction is demonstrated, and its
      quality is estimated. We show that the quality at the first step of prediction is
      approximately 0.7. This indicates that the prediction method is able to model the
      effect of surgery on the healing process, although the random scattering of TM
      data recorded in the examined group is relatively large. The influence of
      periodontal surgery on TM, alone and in combination with systemic metronidazole,
      is quantitatively characterized in two groups of 12 patients each. In the test
      group, which received metronidazole, TM decreased significantly 1 week
      postoperatively, compared to the control group without the antibiotic. The
      gingival fluid flow rate (GFFR) and the percentage of spirochete morphotypes
      detected by darkfield microscopy exhibited a similar dependence. Significant
      differences in TM, GFFR and the percentage of spirochetes between the two groups
      were observed over a period of several weeks. Probing depths (PD) in both groups
      at 2 and 12 months after surgery did not reveal any category with pockets deeper
      than 4 mm. A gain of clinical attachment level of more than 2 mm (CAL) was
      observed at measurements of 16.7% and 10.6% on the test and control groups,
      respectively, 1 year after surgery.

PMID- 11996162
TI  - Human dermal and gingival fibroblasts in a three-dimensional culture: a
      comparative study on matrix remodeling.
AB  - Free-floating collagen lattice is considered a useful tool for assessing wound
      healing in vitro. This work compared extracellular matrix remodeling in collagen
      lattices populated by gingival or dermal fibroblasts. For 21 days we followed gel
      contraction and changes in cell number of collagen lattices seeded with l.5 x
      10(5) fibroblasts of each tissue. We also used indirect immunodetection to study
      extracellular matrix components, metalloproteinases (MMPs), and their tissues
      inhibitors (TIMPs). In addition, the presence of MMPs and TIMPs in the culture
      media was analyzed by zymography and western blotting. No significant difference
      was found concerning gel contraction and changes in cell number. We observed the
      early expression of fibrillin I and collagen type III, apparently codistributed
      and at the end of the gel contraction their disappearance. Concomitantly we
      demonstrated the expression of MMPs and TIMPs, initially localized in cellular
      cytoplasm, then spreading in the extracellular compartment, and even found in the
      culture medium. This remodeling was more rapid and intense with gingival
      fibroblasts than dermal fibroblasts. In conclusion, gingival fibroblasts seem
      more efficient at remodeling the connective tissue than dermal fibroblasts and
      could lead to the better wound healing observed in vivo.

PMID- 11996163
TI  - Expression of amelin and trauma-induced dentin formation.
AB  - According to recent studies, amelin (ameloblastin, sheathlin) is expressed in
      young odontoblasts at the initiation of dentin formation during odontogenesis.
      The purpose of the present investigation was to study whether amelin is also
      expressed at the onset of trauma-induced reparative dentin formation. The
      mandibular developing first molars of 5-day-old rats were surgically taken out,
      and their pulp tissue briefly separated from the inner dentin surface and
      immediately repositioned. Then the teeth were re-implanted in their alveoli. At
      0, 2, 4, 6, 8, 12 or 14 days after surgery, the animals were sacrificed and the
      experimental teeth evaluated by histology and immunohistochemistry for amelin. At
      2, 4, 6 and 8 days after surgery, the detached and traumatized odontoblasts in
      the experimental teeth exhibited increasing signs of degeneration and loss of
      intracellular structures. At days 6 and 8 after surgery, immunohistochemistry
      revealed a strong staining for amelin in the traumatized odontoblastic layer.
      Twelve and 14 days after replantation, only necrotic cell remnants of the
      traumatized odontoblasts were discernible. At this stage, no amelin could be
      detected by immunostaining. A wide zone of an unorganized mineralized tissue
      surrounded the odontoblastic cell remnants. On the pulpal side of the unorganized
      tissue, a new, highly organized tubular reparative dentin layer was observed,
      bordered by columnar odontoblast-like cells abutting on newly formed predentin.
      The results indicate that the initiation of trauma-induced reparative dentin
      formation mimics that of primary dentin formation and that amelin seems to be
      involved in both processes, possibly as a signaling molecule.

PMID- 11996164
TI  - A case-control study on the psychophysical and psychological characteristics of
      the phantom tooth phenomenon.
AB  - The objective of this study was to determine whether patients with phantom tooth
      symptoms have an altered sensory perception as compared to pain-free subjects.
      Ten patients (mean age 56, range 32-71, nine females) were diagnosed as suffering
      from "phantom tooth" according to a specifically designed phantom tooth
      questionnaire including components of the McGill Pain Questionnaire. An SCL-90
      form was completed and assessment of sensory perception was carried out by
      determination of the threshold level for light touch sensation, two-point
      discrimination, and thermal sensation in a case-control design. Results. Of all
      the observed questionnaires, 5.7% seemed to deal with phantom tooth, with a
      female preponderance (ratio 9:1). Complaints were predominantly reported in the
      upper jaw (ratio 8:2) with the majority in the molar region (ratio 5:3). Phantom
      tooth subjects showed significantly lower threshold levels for light touch
      sensation, most markedly on the affected side. The average psychoneurotic profile
      showed a tendency towards higher scores for the phantom tooth subjects.
      Conclusion. The phantom tooth phenomenon may show a number of features which
      might aid differential diagnosis. To verify influences such as upper molar
      predominance and increased light touch sensation, another study should be
      performed on a larger patient sample.

PMID- 11996165
TI  - Primary cutaneous B-cell lymphoma and lymphoproliferative disorders of skin:
      current status of pathology and classification.
AB  - Cutaneous B-cell lymphomas (CBCLs) are rare and are usually secondary to systemic
      nodal lymphoma. These lymphomas account for about 20% of all cutaneous lymphomas.
      Only recently has the existence of B-cell lymphoma presenting clinically in the
      skin without evidence of extracutaneous involvement been accepted as primary
      CBCL. The application of immunohistochemistry and molecular analysis has shown
      that some cases of cutaneous lymphoid hyperplasia and pseudolymphomas contain a
      monoclonal population of B cells and are therefore considered true lymphomas. The
      pathology and classification of this heterogeneous group of lymphoproliferative
      disorders is reviewed. The main entities comprise marginal zone lymphoma,
      lymphoplasmacytoid lymphoma (immunocytoma), follicular center cell lymphoma,
      mantle cell lymphoma, large cell lymphoma (immunoblastic and anaplastic),
      intravascular lymphomatosis, plasmacytoma, and lymphoblastic lymphoma.

PMID- 11996166
TI  - Observer variation, dysplasia grading, and HPV typing: a review.
AB  - Squamous dysplasia of the cervix is a morphologic continuum that is divided into
      a number of categories. When the severity of a morphologic abnormality is
      assessed, whether in a biopsy sample or in an exfoliative smear, there can be
      significant observer variation. The statistical quantification of this variation,
      with particular reference to the kappa statistic and the influence of the number
      of categories utilized on the kappa statistic, is discussed. The contribution of
      information theory to the understanding of the reasons for observer variation is
      explored. The use of a binary (Bethesda) system of classification of squamous
      dysplasia and its validation by comparing consensus diagnoses with human
      papilloma virus type both in biopsy samples and in smears is reviewed.

PMID- 11996167
TI  - Hyperchromatic crowded groups: pitfalls in pap smear diagnosis.
AB  - A problem in the diagnosis of Papanicolaou smears--the interpretation of
      "hyperchromatic crowded groups" (HCGs)--is identified and analyzed. HCGs usually
      represent benign entities such as endometrial cells, syncytial aggregates in
      severe atrophy, or fragments of endocervical tissue, the latter being seen with
      increasing frequency due to the use of the endocervical brush. Tubal metaplasia
      is another common, benign source of HCGs. However, occasionally HCGs represent
      serious lesions, such as carcinoma in situ, invasive squamous cell carcinoma, and
      glandular neoplasia, either in situ or invasive. The distinction among these
      various entities is not always easy, but guidelines are presented.

PMID- 11996168
TI  - Controversies associated with cervical cytologic screening: a physician's view.

PMID- 11996169
TI  - Should we abandon pap smear testing?

PMID- 11996170
TI  - Defending the pap smear: a proactive approach to the litigation threat in
      gynecologic cytology.

PMID- 11996171
TI  - The cytologic diagnosis of low-grade transitional cell carcinoma.
AB  - Current theory suggests that transitional cell carcinoma (TCC) occurs as either
      of 2 disease processes, each of which has a distinct cytologic appearance and
      clinical course: low-grade and high-grade TCC. Urinary cytology has become a
      mainstay technique for monitoring disease recurrence in patients with TCC. Most
      cases of high-grade TCC can be diagnosed accurately in urinary cytology
      specimens. However, the cytologic diagnosis of low-grade TCC is difficult; these
      tumors exhibit subtle cytomorphologic alterations that are difficult to
      distinguish from benign or reactive processes. The cytologic criteria most useful
      for diagnosing low-grade TCC in urinary cytology specimens are reviewed.
      Additionally, the discussion includes some of the new ancillary tests that are
      emerging as possible diagnostic aids for the detection of low-grade urothelial
      neoplasms.

PMID- 11996172
TI  - Cytopathology of pregnancy-induced cell patterns in cervicovaginal smears.
AB  - Considerable interest has been devoted to cytology in pregnancy, especially the
      morphologic changes that may cause problems in differential diagnosis. It is
      surprising that the published discussion of the cytologic appearance of smears
      from pregnant women has been so limited. This review emphasizes that retained
      trophoblastic tissue may be a source of highly atypical appearing cells in the
      cervicovaginal cytology obtained under various clinical conditions.
      Distinguishing between Arias-Stella cells and cells of glandular abnormalities
      can be problematic, since the morphologic characterization of the former is poor.
      This review also emphasizes that a full awareness of the morphology of pregnancy
      as well as of the patient's clinical history are needed for greater precision in
      diagnosing cell patterns as pregnancy-related and not malignant.

PMID- 11996173
TI  - Cytopathology of pleural mesotheliomas.
AB  - Pleural mesothelioma is a rare and highly malignant tumor that has shown
      increasing incidence. In approximately 90% of patients the tumor manifests
      initially as recurrent, unilateral, bloody pleural effusions; in the remaining
      10% of patients the tumor is detected by chest radiography. As a result, pleural
      mesotheliomas can be diagnosed by cytologic examination of pleural effusions or
      transthoracic fine-needle aspirates; the cytologic manifestations of such an
      examination are described in detail. Additionally, the handling of cytologic
      specimens, diagnostic problems, and the value and limitations of
      immunocytochemical and electron microscopic studies and other ancillary
      techniques in the cytologic identification of pleural mesotheliomas are
      discussed.

PMID- 11996174
TI  - Problems in grading soft tissue sarcomas.
AB  - Clinicians, particularly medical oncologists, place increasing importance on
      histologic grading as a means of informing their treatment decisions in patients
      with soft tissue sarcoma. Numerous different grading systems (with a variable
      number of grades) have been described. Although these have often used different
      parameters, it is nevertheless generally accepted that histologic grade, however
      derived, is probably the best prognostic indicator in these sarcoma patients.
      Unfortunately, however, there is no consensus as to the best grading system, and
      even those schemes that are most widely applied (those of the French National
      Cancer Centers and the National Cancer Institute in the United States) have
      important and acknowledged limitations. Furthermore, assessment of many of the
      most popular grading parameters is necessarily subjective, and, to date,
      potentially more objective measures of proliferative activity and ploidy (eg,
      using immunohistochemistry or DNA flow cytometry) have not improved on
      experienced morphologic grading. In addition, the confounding (and often
      misleading) effect on histologic grade of preoperative therapy, which is
      increasingly used, has not been addressed in any meaningful way. This overview
      highlights the limitations, problems, and concerns regarding histologic grading
      of soft tissue sarcomas.

PMID- 11996175
TI  - Low-grade osteogenic sarcoma arising in medullary and surface osseous locations.
AB  - Osteosarcomas represent a heterogeneous group of tumors with different histologic
      and clinical features, biologic behavior, and therapy. Histologic grading has
      remained the most important factor for predicting the clinical progression of
      osteosarcomas. Some of the most common diagnostic problems in surgical pathology
      related to low-grade osteogenic sarcoma are addressed.

PMID- 11996176
TI  - Defective sperm decondensation: a cause for fertilization failure.
AB  - The study aimed to evaluate the role of chromatin packaging (CMA3 staining),
      sperm morphology during sperm-zona binding, sperm decondensation and the presence
      of polar bodies in oocytes that failed in vitro fertilization (IVF). The
      percentage CMA3 staining categorized the data into three groups, < 44%, n = 10; >
      or = 44-59%, n = 10; and > or = 60%, n = 29. Morphology groups were < or = 4% (n
      = 11); > 4-14% (n = 19); and > 4% (n = 19). One hundred and seventy-two oocytes
      that failed IVF were evaluated for sperm-zona binding, ooplasma penetration and
      sperm decondensation. Odds ratio analyses indicated that being in the > or = 60%
      CMA3 staining group resulted in a 15.6 fold increase in the risk of
      decondensation failure, relative to CMA3, staining of < 44%. For morphology,
      there was a 2.17 fold decrease in the risk of fertilization failure in the
      morphology group with > 4-14% normal cells, while it increased 2.45 fold for the
      morphology group with < or = 4% normal cells. Using CMA3 fluorescence to
      discriminate, 51% of the oocytes in the group with elevated CMA3 fluorescence had
      no sperm in the ooplasma compared to 32% and 16% penetration failure in the CMA3
      staining groups > or = 44-59% and < 44%, respectively. Sperm chromatin packaging
      quality and sperm morphology assessments are useful clinical indicators of human
      fertilization failure. Immunofluorescence techniques could be used to provide a
      clear diagnosis of failed fertilization.

PMID- 11996177
TI  - Effects of dexamethasone on proliferation of and fibronectin synthesis by human
      primary prostatic stromal cells in vitro.
AB  - Glucocorticoids are anti inflammatory stress hormones and have been suggested to
      be involved in a large number of pathological processes. To test the effects of
      glucocorticoids on stromal prostatic cell growth and proliferation in vitro, the
      influence of a synthetic glucocorticoid (dexamethasone, dex) on recently
      established human primary cells from prostatic stroma (hPCPs) was analysed. The
      localization and distribution of the glucocorticoid receptor (GR) was
      investigated by immunohistochemistry. In addition, expression of the active
      isoform of the receptor (alpha-GR) was examined by reverse transcription PCR, and
      the effect of different doses of dex on proliferation of the stromal cells
      evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      (MTT) and amido black assays. alpha-GR mRNA was expressed by the hPCPs, and the
      GR protein was detected in the cytoplasm and nucleus of these cells. Incubating
      the cells with dex resulted in an enhanced cell proliferation that was mainly
      restricted to the fibroblasts. Moreover, fibronectin (FN) gene expression and
      secretion of the protein was increased by high doses of dex (> or = 10(-8) M),
      whereas low doses of dex (10(-10)M) showed no effect. Human prostatic stromal
      cells show sensitivity to dex in vitro, resulting in an increase in cell
      proliferation and FN synthesis. The authors assume that locally accumulating
      glucocorticoids can also influence the regulation of cell growth and
      extracellular matrix synthesis in the human prostate in vivo and may play a role
      in the pathologically altered prostate.

PMID- 11996178
TI  - Sexual activity, sexual and partnership satisfaction in ageing men--results from
      a German representative community study.
AB  - Age-related changes in men have only recently received widespread scientific
      attention. Although a reduction in sexual interest and satisfaction are common in
      the 'ageing male', little is known about sexual activity and satisfaction in the
      general population. We therefore investigated age-related changes in men's sexual
      activity, and their sexual and partnership satisfaction. We also tried to
      identify psychosocial determinants of sexual and partnership satisfaction. A
      representative community-based sample of 1299 men between 18 and 92 years was
      interviewed, based on a set of standardised questionnaires, on life satisfaction,
      physical complaints, personality and interpersonal problems. Comparing the 3 age
      groups (18-40, 41-60, 61-92 years), we found the proportion of sexually active
      men to be fairly constant up to the age of 60 (84-85%); while above the age of
      60, the proportion declined to 51%. The proportion of men without a partner (32%
      of the total sample) who were sexually active was lower; in this group sexual
      activity started to decline between 41 and 60 years (from 74% to 56%), and
      comparably fewer older men without a partner were sexually active (17%). We also
      found an age-related decline in sexual satisfaction, and a slight increase in
      partnership satisfaction. Sexual activity was a major determinant of sexual
      satisfaction; sexual and partnership satisfaction were compromised in men who
      were dissatisfied with their health, and reported somatoform complaints and
      interpersonal problems. Our results emphasise the contribution of psychosocial
      factors to declining sexual activity and satisfaction. Future studies in the
      ageing male should take account of existence and quality of a partnership, and
      recent sexual activity.

PMID- 11996179
TI  - Increased plasma endothelin levels in patients with male hypogonadism.
AB  - Endothelin has various paracrine and endocrine effects on the male reproductive
      system. Testosterone is probably responsible for the higher endothelin levels in
      males. In addition, there is much ambiguity about the relationship between
      gonadotrophic hormones and endothelin. In order to study in more detail the
      relationship of endothelin with the hypothalamo-pituitary-gonadal axis in the
      male, we investigated 18 male patients with various forms of hypogonadism (seven
      with hypergonadotrophic hypogonadism and 11 with hypogonadotrophic hypogonadism).
      Eight age-matched healthy males served as controls. The basal endothelin levels
      in patients with hypogonadism (0.95 +/- 0.53 fmol ml(-1)) were significantly
      higher than those of the controls (0.54 +/- 0.06 fmol ml(-1); P < 0.05). Males
      with hypergonadotrophic hypogonadism had significantly increased endothelin
      concentrations (1.05 +/- 0.57 fmol ml(-1); P < 0.05), whereas those with
      hypogonadotrophic hypogonadism (0.89 +/- 0.53 fmol ml(-1)) had nonsignificantly
      (P > 0.05) elevated levels. No significant correlation was found between plasma
      endothelin levels and gonadotrophin, prolactin and testosterone concentrations.
      The results of this study suggest that plasma endothelin levels are increased in
      males with hypogonadism.

PMID- 11996180
TI  - Involvement of apoptosis in the control of Sertoli and pre-meiotic germ cell
      numbers in the developing rabbit testis.
AB  - The numbers of Sertoli and pre-meiotic germ cells in the developing rabbit testis
      were investigated as an initial step in determining the physiological meaning of
      the control of cell number in the testis by apoptosis. Sections were stained
      immunohistochemically for the detection of apoptotic cells and counterstained
      with haematoxylin. The number resulting from subtraction of the number of
      apoptotic cells from the total cell number was defined as the viable cell number.
      The number of viable premeiotic germ cells in the adluminal compartment of
      seminiferous tubules decreased during the pre-natal period, although neither
      apoptotic nor necrotic figures were detected. After birth, the numbers of total
      and apoptotic Sertoli and pre-meiotic germ cells increased, maintaining a stable
      ratio of their viable cell populations until the induction of meiosis. During
      induction of meiosis, the increase in the number of viable Sertoli cells was
      significantly accelerated because of the rapid decrease in the number of
      apoptotic Sertoli cells. Just after spermatids were formed the number of viable
      spermatogonia increased, reflecting an active supply of differentiated sper
      matogonia entering meiosis. In conclusion, apoptosis of Sertoli and pre-meiotic
      germ cells plays an important role in the acquisition of a suitable ratio of both
      cell types, and in providing intratubular environments for further progression of
      spermatogenesis, by controlling numbers of both cell types during the post-natal
      period.

PMID- 11996181
TI  - Post-natal development of the rat testis: steroid hormone receptor distribution
      and extracellular matrix deposition.
AB  - The control of testicular development and differentiation depends on hormones and
      a variety of cell-cell interactions mediated mainly by paracrine factors. In the
      second and third weeks of post-natal development important changes take place in
      the rat testis, e.g. the tubular lumen starts to open on post-natal day 10, the
      blood-testis barrier starts to form on day 15, and Sertoli cell proliferation
      ceases on day 15. In the present study the expression in different testicular
      compartments of the androgen receptor (AR), progesterone receptor (PR), and
      extracellular matrix proteins such as laminin, entactin-1 (nidogen-1) and
      fibronectin, during post-natal development was examined using
      immunohistochemistry and semiquantitative image analysis. An intratubular AR peak
      on days 14-17, an increase in intratubular PR expression on days 14-16, and an
      increase in peritubular entactin-1 expression during the second and third weeks
      post-partum are demonstrated. These results suggest that a variety of changes
      occur at the cellular level during this period when certain milestones of
      testicular development occur, substantiating the hypothesis of a particular role
      for paracrine interactions during the development of the rat testis.

PMID- 11996182
TI  - Extracellular signal-regulated kinase activation involved in human sperm-zona
      pellucida binding.
AB  - In a previous study involving the inhibition the mitogen-activated protein kinase
      (MAPK), extracellular signal regulated kinase (ERK), we found that the very
      specific MAPK kinase (MEK) inhibitor, PD098059, inhibited the zona pellucida (ZP)
      induced acrosome reaction. As an intact acrosome on the spermatozoa is a
      prerequisite in ensuring tight binding to the ZP, we investigated the zona
      binding potential of spermatozoa after PD098059 treatment of sperm, followed by
      exposure to solubilised human ZP and calcium ionophore (A23187). PD098059 treated
      spermatozoa, exposed to solubilised ZP, bound significantly more to the ZP, as
      compared to control spermatozoa also exposed to solubilised ZP (26.5 +/- 3.7 vs.
      13.8 +/- 2.8, P < 0.05). No significant differences in binding to the ZP were
      observed between PD098059 treated and untreated sperm populations after A23187
      exposure. These results can be interpreted to support the idea that the ZP
      induced AR is the physiologically relevant exocytotic event, as it is the ZP
      induced AR, and not the spontaneous (culture medium) or A23187 induced AR, that
      appears to be mediated through an ERK-mediated signal transduction process.

PMID- 11996183
TI  - Why do we continue to determine alpha-glucosidase in human semen?

PMID- 11996184
TI  - Characterizing the deformed state in Al-0.1 Mg alloy using high-resolution
      electron backscattered diffraction.
AB  - The application of high resolution electron backscatter diffraction (EBSD) in a
      field emission gun scanning electron microscope to the characterization of a
      deformed aluminium alloy is discussed and the results are compared with those
      obtained by transmission electron microscopy. It is shown that the adequate
      spatial resolution, accompanied by the improvement in angular resolution to
      approximately 0.5 degrees that can be achieved by data processing, together with
      the extensive quantitative data obtainable, make EBSD a suitable method for
      characterizing the cell or subgrain structures in deformed aluminium. The various
      methods of analysing EBSD data to obtain subgrain sizes are discussed and it is
      concluded that absolute subgrain reconstruction is the most accurate.

PMID- 11996185
TI  - Characterization of nitride thin films by electron backscatter diffraction.
AB  - Thin films incorporating GaN, InGaN and AlGaN are presently arousing considerable
      excitement because of their suitability for UV and visible light-emitting diodes
      and laser diodes. However, because of the lattice mismatch between presently used
      substrates and epitaxial nitride thin films, the films are of variable quality In
      this paper we describe our preliminary studies of nitride thin films using
      electron backscattered diffraction (EBSD). We show that the EBSD technique may be
      used to reveal the relative orientation of an epitaxial thin film with respect to
      its substrate (a 90 degrees rotation between a GaN epitaxial thin film and its
      sapphire substrate is observed) and to determine its tilt (a GaN thin film was
      found to be tiltedby 13 +/- 1 degrees towards [1010]GaN), where the tilt is due
      to the inclination of the sapphire substrate (cut off-axis by 10 degrees from
      (0001)sapphire towards (1010)sapphire). We compare EBSD patterns obtained from As
      doped GaN films grown by plasma-assisted molecular beam epitaxy (PA-MBE) with low
      and high As4 flux, respectively. Higher As4 flux results in sharper, better
      defined patterns, this observation is consistent with the improved surface
      morphology observed in AFM studies. Finally, we show that more detail can be
      discerned in EBSD patterns from GaN thin films when samples are cooled.

PMID- 11996186
TI  - Characterization of textured NiO films for application as buffer layers in high
      temperature superconducting tapes.
AB  - Textured NiO films have been grown, by thermal oxidation, on biaxially textured
      Ni substrates. The films have been characterized by X-ray diffraction (XRD),
      scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD).
      The XRD results showed two texture components, cube texture (001)[100] and (111)
      with out of plane orientation only. SEM showed much inhomogeneity of grain size
      on the sample surface. Analysis by EBSD revealed that coarse grained regions were
      cube textured and fine grained regions were <111> fibre textured. The ability to
      correlate textural and microstructural data is crucial to the optimization of
      textured NiO films for use in coated conductor technology.

PMID- 11996187
TI  - Crystallographic orientation of ZrB2-ZrC composites manufactured by the spark
      plasma sintering method.
AB  - The crystallographic grain orientation of ZrB2-ZrC composites manufactured using
      a spark plasma sintering (SPS) method, a new sintering technique in development
      for poorly sinterable ceramic materials, was analysed by the scanning electron
      microscopy-electron backscattered diffraction (SEM-EBSD) method. Their
      crystallographic features have been compared with those of a conventionally
      sintered specimen using a pressureless sintering (PLS) method. In the composite
      sintered by PLS, (0001) planes of ZrB2 were orientated in the direction parallel
      to the specimen surface (RD) but (1010) and (2110) planes randomly orientated. In
      the case of SPS, (0001) planes of ZrB2 were orientated normal to the specimen
      surface (ND) and weakly to the RD. In both cases of PLS and SPS, ZrC grains had a
      randomly orientated grain structure. The distribution of grain boundary
      misorientation of PLS and SPS-processed composites showed the same tendency that
      high-angle boundaries were more prevalent than low-angle boundaries. But in the
      case of ZrC grains in the SPS sample, the proportion of CSL boundaries with low
      sigma value (3, 5, 7, 9, 11) was relatively larger.

PMID- 11996188
TI  - Extracting twins from orientation imaging microscopy scan data.
AB  - Automated electron backscatter diffraction or orientation imaging microscopy
      (OIM) provides spatially specific measurements of crystallographic orientation.
      These measurements are typically collected on regular grids. By inspecting the
      misorientation between neighbouring measurements on the grid, potential twin
      boundaries can be identified. If the misorientation is within some given
      tolerance of a specified twin misorientation, the boundary separating the two
      measurements may be identified as a potential twin boundary. In addition, for a
      coherent twin, the twinning planes must be coincident with the grain boundary
      plane. As OIM scans are inherently two-dimensional, the scan data provide only
      limited information on the boundary plane. Thus, it is not possible to ascertain
      definitively whether the twinning planes are coincident with the boundary plane.
      Nonetheless, the alignment of the surface traces of the twinning planes with the
      trace of the boundary provides a partial indication of coincidence. An automated
      approach has been developed that allows data concerning both twin criterion to be
      extracted from OIM scans. Application of the methodology to deformed zirconium
      suggests that the twinning planes remain coherent during deformation. The
      methodology was also used to improve grain size distributions measured by OIM.
      These results more closely match those obtained by conventional metallography.

PMID- 11996189
TI  - Single-section plane assessment in grain boundary engineered brass.
AB  - The present paper reports a comparative analysis of sigma 3 (in the coincidence
      site lattice notation) grain boundary types, in two grain boundary engineered
      brass specimens, by use of electron backscatter diffraction (EBSD) data coupled
      to the measurement of boundary traces in a single section. Although most of the
      data were analysed using the new single-section technique, an analysis of
      boundary plane orientations in three dimensions was made in a subset of the data
      in order to validate the single section methodology. The single-section trace
      analysis procedure. coupled with EBSD, is a viable and robust tool for analysis
      of sigma 3 grain boundary planes. The procedure provides data which suggest that
      part of the enhanced strain-to-failure in specimen B compared to specimen A is
      the result of an increased proportion of mobile sigma3 boundaries, i.e. those
      which are displaced from the [111] symmetrical tilt configuration.

PMID- 11996190
TI  - Is fast mapping good mapping? A review of the benefits of high-speed orientation
      mapping using electron backscatter diffraction.
AB  - Orientation mapping using automated electron backscatter diffraction (EBSD) is
      now a common technique for characterizing microstructures. Improvements in
      software and hardware have resulted in high-speed mapping capabilities above
      80,000 points h(-1). For 'routine' microstructural analyses of materials such as
      steel and aluminium (e.g. texture and grain size measurements and high angle
      boundary characterization), high-speed orientation mapping is an ideal approach
      with minimal penalty on the final statistics. However, for the accurate analysis
      of very low angle boundaries and for routine analyses of more difficult materials
      (e.g. most rock samples), we advocate a more patient approach to orientation
      mapping with an emphasis on data accuracy and reliability. It is important that
      the objectives of any EBSD analysis are carefully considered before starting--in
      this way the maximum potential of an EBSD system can be achieved.

PMID- 11996191
TI  - A preliminary electron backscattered diffraction study of sintered NdFeB-type
      magnets.
AB  - This paper reports, for the first time, the use of electron backscattered
      diffraction (EBSD) to study orientation in sintered NdFeB type magnets. The
      magnetic properties of NdFeB magnets are greatly improved if a strong
      crystallographic texture is firstly achieved, namely, the direction of the c-axis
      is along the direction of magnetization. A systematic survey of sample
      preparation techniques showed that samples that were mechanically polished and
      then etched gave the most reliable EBSD data. Analyses were made using both fully
      automated EBSD scans and by EBSD measurements taken after manual movement of the
      beam. The EBSD results are presented as secondary electron SEM micrographs,
      orientation images and 001 pole figures. For the selection of grains
      investigated, the deviation of the c-axis was shown to be between 10 degrees and
      30 degrees from the ideal [001]//magnetization direction. It is demonstrated that
      EBSD is a valuable tool for characterizing the microstructure and texture
      relationships and for assessing the performance of the processing routes of NdFeB
      magnets.

PMID- 11996192
TI  - Application of electron backscatter diffraction (EBSD) to fracture studies of
      ferritic steels.
AB  - The application of electron backscatter diffraction (EBSD) to fracture studies
      has provided a new method for investigating the crystallography of fracture
      surfaces. The crystallographic indices of cleavage planes can be measured both
      directly from the fracture surface and indirectly from metallographic sections
      perpendicular to the plane of the adjoining fracture surfaces. The results of
      direct individual cleavage facet plane orientation measurements are presented for
      carbon-manganese (C-Mn) and low-alloy Mn-Mo-Ni (similar to ASTM A553 type-B).
      Pressure vessel steel weld metals, obtained from fracture surfaces of Charpy
      impact test specimens fractured at various test temperatures and for an ultra-low
      carbon steel (Fe-0.002C- 0.058P) fractured at -196 degrees C by impact. In
      addition to the direct measurement from the fracture surface, cleavage facet
      orientation measurements for the ultra-low carbon steel were complemented by the
      results obtained from the metallographic sections. Fractographic observations
      revealed that cleavage fracture is accommodated by a microvoid coalescence
      fracture micromechanism, which was induced by decohesion of second phase
      particles (inclusions). The correlation between the direct and indirect
      methodologies shows that the cleavage facet planes are dominated by the [001]
      plane orientations, and indicated that even when information concerning the full
      five degrees of freedom is inaccessible, the cleavage facet plane could still be
      determined. Finally, the advantages and disadvantages of direct orientation
      measurements from the fracture surface and indirectly by a destructive sectioning
      technique are discussed.

PMID- 11996193
TI  - Misorientation distributions in hot deformed NaCl using electron backscattered
      diffraction.
AB  - EBSD orientation mapping has been used to derive subgrain boundary misorientation
      distributions in a series of hot deformed and etched NaCl samples. The main
      objective of this study has been to examine the influence of data processing,
      noise caused by angular resolution limits and step size on the subgrain
      misorientation distributions in hot deformed NaCl. Processing of non-indexed EBSD
      patterns increased the average misorientations in etched NaCl. Noise contributed
      significantly to low angle misorientation peaks for step sizes less than the
      minimum subgrain size. Orientation data collected using a step size larger than
      the average subgrain size cumulated misorientations across individual subgrains
      and effectively measured an orientation gradient between steps. Orientation
      gradient distributions were not influenced by noise. Average misorientation
      values calculated from large step data correlated well with average
      misorientation from small step size data, Average misorientations showed a power
      law relationship with strain. Three types of substructures were identified using
      scanning electron microscopy and EBSD mapping, equiaxed subgrains, long subgrain
      boundaries and a core-mantle subgrain arrangement.

PMID- 11996194
TI  - The status of hypertension therapy.

PMID- 11996195
TI  - Fixed low-dose combination in first-line treatment of hypertension.
AB  - Hypertension is poorly controlled in most patients. The control rate, defined as
      a systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) <
      90 mmHg, is 27% in the USA, despite data documenting the reduction of
      cardiovascular events by treating diastolic hypertension and isolated systolic
      hypertension. Control rate is even lower for patients with renal insufficiency
      and type 2 diabetes mellitus. Thus, monotherapy is unlikely to achieve blood
      pressure control. Supported by the 6th Joint National Committee Report (JNC VI),
      interest has been sparked in the use of fixed low-dose combination drugs as first
      line treatment of hypertension. The rationale is to enhance hypertension control
      by using drugs that are additive while avoiding complex regimens that result in
      non-compliance. When low doses of two drugs are used, adverse drug reactions are
      fewer compared with the maximal dose of each drug tested separately.
      Multifactorial trials document the efficacy of hydrochlorothiazide (HCTZ) 6.25 mg
      in combination with bisoprolol 2.5-10 mg once daily. DBP control rates have been
      64-77% and equal to or superior to HCTZ 25 mg once daily, amlodipine 2.5-10 mg
      once daily, enalapril 5-40 mg once daily or losartan 50-100 mg and losartan 50 mg
      with 12.5 mg HCTZ once daily. This low-dose combination has a side-effect profile
      similar to placebo. Erectile dysfunction and hypokalaemia are uncommon. Fixed
      dose combination antihypertensive drugs simplify dosing regimens, improve
      compliance, improve hypertension control, decrease dose-dependent side-effects,
      and reduce cost as the first-line treatment of hypertension.

PMID- 11996196
TI  - Clinical results with bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg combination
      in systolic hypertension in the elderly.
AB  - Hypertension in the elderly, especially systolic hypertension, has been
      recognized as a major cardiovascular risk factor. Several international studies,
      using primarily diuretics and/or beta-blockers, have shown the benefits of
      antihypertensive treatment in elderly patients in terms of cardiovascular
      morbidity and mortality reduction. However, because the risk of side-effects is a
      major concern when treating the elderly, the use of low-dose combination
      treatments may be of particular interest. A randomized, multicentre, double
      blind, parallel group study was conducted to compare the efficacy and safety of
      bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg (biso 2.5/HCTZ 6.25) (n = 84)
      versus amlodipine 5 mg (n = 80) in subjects over 60years of age with isolated
      systolic hypertension. The effects of these two treatment strategies on patients'
      quality of life were also assessed. After a two- to four-week placebo washout
      period, both drugs were administered once daily and taken for 12 weeks. Blood
      pressure was measured 24 h after treatment administration. Systolic blood
      pressure/diastolic blood pressure changes from baseline to week 12 were similar
      for both biso 2.5/HCTZ6.25 and amlodipine (-20.0/-4.5 mmHg and -19.6/-2.4 mmHg,
      respectively). Overall adverse events for biso 2.5/HCTZ 6.25 and amlodipine were
      39% and 40%, respectively. Both treatments improved quality of life scores in the
      same way. This study demonstrates comparable efficacy and tolerability of biso
      2.5/HCTZ 6.25 and amlodipine. Low-dose combination of bisoprolol and
      hydrochlorothiazide may be an appropriate alternative for elderly patients with
      systolic hypertension.

PMID- 11996197
TI  - Current recommendations for the treatment of hypertension: are they still valid?
AB  - Recent trials have helped to clarify indications for the initial pharmacological
      therapy of hypertension. Both the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World
      Health Organization-international Society of Hypertension (WHO-ISH)
      recommendations should be revised. The more recent trials indicate that: (1)
      diuretics and beta-blockers appear to be as effective in reducing overall
      morbidity/ mortality as other agents (Swedish Trial in Old Patients with
      Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS],
      Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem
      [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events,
      especially congestive heart failure, when compared with a diuretic
      (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the
      use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer
      myocardial infarctions and episodes of heart failure than calcium channel
      blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine
      Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure
      Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project
      [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic
      patients; (4) overall cardiovascular events are similar with calcium channel
      blockers compared with a diuretic - however, there are fewer strokes with non
      dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase
      in heart failure and myocardial infarctions with either a dihydropyridine or non
      dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT,
      NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and
      slow progression of renal disease in type 2 diabetic patients when compared with
      regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints
      in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II
      Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with
      Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High
      risk hypertensive patients should probably be treated initially with combination
      therapy, one of which should be a diuretic. The use of diuretics and beta
      blockers as well as ACE-inhibitors alone or with a diuretic should be considered
      as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for
      special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH
      recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be
      considered as preferred therapy in hypertensive diabetic patients. Some data
      suggest equal or greater reduction in strokes with a calcium channel blocker than
      other medications.

PMID- 11996198
TI  - Is there an age at which we should stop performing screening pap smears and
      mammography?

PMID- 11996199
TI  - Statins and osteoporosis: can these lipid-lowering drugs also bolster bones?
AB  - The statins may not only lower cholesterol, they may stimulate bone formation, as
      suggested by a number of observational studies and animal research. Whether these
      drugs will be of benefit in treating osteoporosis awaits further clinical trials.

PMID- 11996200
TI  - How to prevent, recognize, and treat drug-induced nephrotoxicity.
AB  - Many drugs can injure the kidneys, but they cause renal injury via only a few
      common mechanisms. Many patients who develop renal injury after drug exposure
      have identifiable risk factors that could be modified or that should preclude the
      use of these drugs in the first place.

PMID- 11996201
TI  - The case for more aggressive screening and treatment of mild thyroid failure.
AB  - "Subclinical" (mild) thyroid failure is not benign: it tends to progress to overt
      thyroid failure and it has adverse clinical effects. We believe it should be
      screened for more aggressively in the general population, and treated with
      levothyroxine.

PMID- 11996202
TI  - Improving the care of patients dying of heart failure.
AB  - Patients with heart failure have special palliative care needs, but palliative
      measures for treating the symptoms of end-stage heart failure have been largely
      ignored. A formal disease-management program for heart failure should include
      palliative care.

PMID- 11996203
TI  - Management of smell and taste problems.
AB  - Lost or impaired smell or taste should be taken seriously, as it puts a person at
      higher risk for toxic exposures, such as gas leaks, smoke, and rotting food, and
      it also takes away the enjoyment of some of life's pleasures, such as the
      fragrance of flowers or the taste of good food or fine wine. In many patients,
      the loss follows a viral upper respiratory tract infection, and the only real
      treatment is to reassure patients that the problem may resolve if the damaged
      sensory cells regenerate. In other patients, the loss has more subtle causes and
      deserves a careful investigation and appropriate treatment. This article reviews
      the proper steps to take when investigating and treating chemosensory
      difficulties.

PMID- 11996204
TI  - Sudden weakness in a patient with lymphoma.

PMID- 11996205
TI  - A practical guide for examining and treating the diabetic foot.
AB  - Physicians can perform a quick, complete examination of the feet of patients with
      diabetes to prevent serious complications. The examination should focus on
      circulation, nerve function, musculoskeletal problems, and the skin. All patients
      should be urged to wear supportive, comfortable shoes, and to wash, moisturize,
      and examine their feet every day.

PMID- 11996206
TI  - Patient information. Taking care of your feet.

PMID- 11996207
TI  - Effects of antiplatelet agents on platelet-induced thrombin generation.
AB  - OBJECTIVES: The influence of antiplatelet agents on platelet-induced thrombin
      generation may increase the risk of bleeding. Assessment of the endogenous
      thrombin potential (ETP), is therefore a parameter deserving attention in early
      pharmacodynamic studies with antiplatelet drugs. The aim ofthis study was to
      assess whether an automated ETP-assay can be used to determine possible
      inhibitory effects of antiplatelet drugs on platelet-associated thrombin
      generation. METHODS: We first characterized the in vitro dose-response
      relationship of several platelet agonists (ADP, collagen, U46619, TRAP (amino
      acid sequence: SFLLRNP) and tissue factor (TF) using the generation of ETP. One
      submaximal concentration of each agonist was then used to assess the influence of
      in vivo treatment with aspirin (single oral dose of 500 mg as inhibitor of
      thromboxane synthesis) and clopidogrel (given orally for 6 days, as an inhibitor
      of the purinergic P2Y12-receptor on platelets) and in vitro treatment with
      abciximab (which inhibits the platelet glycoprotein IIb/IIIa-receptor for
      fibrinogen), on the ETP. RESULTS: The effect of TF and the other platelet
      inducers on thrombin generation was dose-dependent. Repeat measurements on
      samples from the same subject, with the same inducer concentration on 2 different
      occasions showed a variability of approx. 22% (absolute difference between 2
      measurements as % of mean). The coefficient on variation of repeat measurements
      of one sample varied between 7% and 17%, depending on the inducer. After a single
      dose of aspirin, ETP was reduced by 25-40%, depending on the platelet activating
      agent used. The reduction in ETP with abciximab in vitro was more pronounced. In
      contrast, TF-induced ETP was not influenced by aspirin or abciximab. Clopidogrel,
      administered for 6 days, reduced the ETP by 60% when platelets were stimulated
      using 20 microM ADP, whereas collagen-induced ETP and TF-induced ETP remained
      unchanged. CONCLUSIONS: The ETP-method is a sensitive and reproducible method for
      the detection of drug effects on platelet-induced thrombin generation of high
      throughput, and can be recommended for studies on the pharmacodynamic profile of
      drugs interfering with platelet function.

PMID- 11996208
TI  - Elimination of levofloxacin in critically ill patients with renal failure:
      influence of continuous veno-venous hemofiltration.
AB  - OBJECTIVES: Pharmacokinetic data on levofloxacin in critically ill patients are
      sparse and conflicting. Aim of the study was to assess the clearance of
      levofloxacin in critically ill patients treated with continuous veno-venous
      hemofiltration (CVVH). METHODS: Pharmacokinetics of levofloxacin were studied in
      11 critically ill patients. Four patients were treated with CVVH because of renal
      failure, 4 patients had moderately impaired renal function but were not on
      hemofiltration, and 3 patients had approximately normal renal function. Patients
      received 0.5 g levofloxacin infused over 0.5 hours. Plasma levels of levofloxacin
      were determined by HPLC and pharmacokinetic parameters were calculated using a
      non-compartmental model. RESULTS: Levofloxacin clearance in critically ill
      patients with approximately normal renal function was similar to that in healthy
      subjects. In critically ill patients with impaired renal function not on CVVH,
      mean half-life was prolonged by a factor of about 3 (20-25 hours). The mean
      residence time and the volume of distribution were also increased. In renal
      failure treated with CVVH, a wide variability in pharmacokinetics was seen. The
      half-life was about 30 hours and the mean levofloxacin clearance was raised by a
      factor of 2. The area under the concentration-time curve was reduced by
      hemofiltration, while the volume of distribution was increased. There was a
      positive correlation between blood flow through the hemofilter and levofloxacin
      clearance. Variable amounts of the drug were recovered from the hemofilter. Most
      plasma levels, however, were in the therapeutic range and drug accumulation to
      toxic plasma concentrations was not observed in renal failure patients undergoing
      CVVH and receiving single daily administration of 0.5 g of levofloxacin i.v.
      CONCLUSIONS: During CVVH using polysulfone membrane hemofilters, plasma
      concentrations of levofloxacin are not easily predictable. Levofloxacin clearance
      may be affected by binding to secondary membranes formed in hemofilters during
      CVVH and blood flow rates have a significant impact on the pharmacokinetics of
      levofloxacin.

PMID- 11996209
TI  - Effect of two oral contraceptives containing ethinylestradiol and levonorgestrel
      on serum and urinary surrogate markers of endothelial function.
AB  - OBJECTIVE: To investigate the effect of two oral contraceptives containing 0.02
      mg ethinylestradiol and 0.1 mg levonorgestrel (Formulation A, Leios), and the
      other containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel (Formulation
      B, Stediril 30) on the serum and urinary concentrations of various markers
      reflecting the status of vascular tone and development of atherosclerosis. The
      adhesion molecules E-selectin, inter-cellular adhesion molecule-1 (ICAM-1),
      vascular cell adhesion molecule-1 (VCAM-1), and homocysteine were included as
      serum markers and cGMP, prostacyclin and its antagonist thromboxane as urinary
      markers. METHODS: In a comparative, double-blind, randomized, parallel group
      study, 34 women received formulation A and 33 women formulation B. Serum samples
      were collected before treatment and after 3, 6 and 12 cycles. Nocturnal urine was
      collected before treatment and during cyclic treatment after 3 and 12 cycles.
      Serum and urinary markers were measured by enzyme immunoassays. RESULTS: E
      selectin levels were significantly reduced by both contraceptives after 3, 6 and
      12 months compared to pretreatment levels. A slight increase in ICAM
      concentrations was observed for both contraceptives after 6 cycles, but this fell
      to pretreatment levels after 12 cycles. VCAM values were significantly lowered
      after 3, 6 and 12 months by both contraceptives. No significant changes were
      found in serum levels of homocysteine. No significant differences were found
      between treatment groups for the serum markers. Both contraceptives significantly
      enhanced urinary cGMP excretion after 12 cycles. The prostacyclin metabolite
      remained unchanged in the case of both formulations, but the excretion of the
      thromboxane metabolite was significantly decreased after 12 cycles. Thus, the
      ratio of prostacyclin to thromboxane, decisive for the resulting effect on
      vascular tone, increased significantly. CONCLUSION: These results indicate that
      the low-dose oral contraceptives can reduce the production of adhesion molecules
      which play a crucial role in the early stages of atherosclerosis. In addition,
      these contraceptives can shift the balance of vascular tone towards dominance of
      vasodilatory substances after 12 cycles of treatment. Thus, the positive
      influence of these contraceptives on the various markers investigated may improve
      vascular tone and impede development of atherosclerosis.

PMID- 11996210
TI  - A review of the French maritime pine bark extract (Pycnogenol), a herbal
      medication with a diverse clinical pharmacology.
AB  - OBJECTIVES: An increasing body of evidence indicates that Pycnogenol (PYC), a
      standardized extract of French maritime pine bark, has favorable pharmacological
      properties. This is a review of studies with both PYC and components of the
      preparation, that have helped to elucidate target sites and possible mechanisms
      for activity in men. METHODS: Studies appearing in peer reviewed literature, as
      well as results presented at international meetings not yet available as
      published papers, are included in this review. Additional data from published
      sources in German and French languages that are not widely available are also
      included. RESULTS: Chemical identification studies showed that PYC is primarily
      composed of procyanidins and phenolic acids. Procyanidins are biopolymers of
      catechin and epicatechin subunits which are recognized as important constituents
      in human nutrition. PYC contains a wide variety of procyanidins that range from
      the monomeric catechin and taxifolin to oligomers with 7 or more flavonoid
      subunits. The phenolic acids are derivatives of benzoic and cinnamic acids. The
      ferulic acid and taxifolin components are rapidly absorbed and excreted as
      glucuronides or sulphates in men, whereas procyanidins are absorbed slowly and
      metabolized to valerolactones which are excreted as glucuronides. PYC has low
      acute and chronic toxicity with mild unwanted effects occurring in a small
      percentage of patients following oral administration. Clinical studies indicate
      that PYC is effective in the treatment of chronic venous insufficiency and
      retinal micro-hemorrhages. PYC protects against oxidative stress in several cell
      systems by doubling the intracellular synthesis of anti-oxidative enzymes and by
      acting as a potent scavenger of free radicals. Other anti-oxidant effects involve
      a role in the regeneration and protection of vitamin C and E. Anti-inflammatory
      activity has been demonstrated in vitro and in vivo in animals. Protection
      against UV-radiation-induced erythema was found in a clinical study following
      oral intake of PYC. In asthma patients symptom scores and circulating
      leukotrienes are reduced and lung function is improved. Immunomodulation has been
      observed in both animal models as well as in patients with Lupus erythematosus.
      PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by
      increasing the activity of endothelial nitric oxide synthase. Dilation of the
      small blood vessels has been observed in patients with cardiovascular disease,
      whereas in smokers, PYC prevents smoking-induced platelet aggregation and reduces
      the concentration of thromboxane. The ability to inhibit angiotensin-converting
      enzyme is associated with a mild antihypertensive effect. PYC relieves
      premenstrual symptoms, including abdominal pain and this action may be associated
      with the spasmolytic action of some phenolic acids. An improvement in cognitive
      function has been observed in controlled animal experiments and these findings
      support anecdotal reports of improvement in ADHD patients taking PYC supplements.
      CONCLUSIONS: There is much evidence showing that PYC has beneficial effects on
      physiological functions. Results from ongoing clinical research are required to
      confirm and extend previous observations.

PMID- 11996211
TI  - Analysis of formulation and food effect on the absorption of metoclopramide.
AB  - OBJECTIVES: Assessment of the relative and absolute bioavailability of immediate
      release and sustained release formulations of metoclopramide. Assessment of the
      effect of a high-fat meal on the pharmacokinetics of sustained release
      metoclopramide. MATERIAL AND METHODS: In a balanced 4-way crossover study in 16
      healthy male volunteers, a sustained release (SR) formulation of metoclopramide
      was compared with a solution for injection (A) and an immediate release tablet
      (B). The SR formulation was administered after a fasting period (C) as well as
      after a high-fat meal (D). A single dose of 30 mg metoclopramide was investigated
      in each treatment. Metoclopramide concentrations were determined by HPLC.
      RESULTS: The absolute bioavailability of the sustained release formulation
      (fasting state) was 58% and thus about 17% lower than the bioavailability of the
      immediate release formulation. Comparing the treatments C (sustained release,
      fasting state) and D (sustained release, high-fat meal) no significant influence
      of food on the absorption of sustained release metoclopramide could be detected.

PMID- 11996212
TI  - Methylphenidate bioavailability from two extended-release formulations.
AB  - OBJECTIVE: The objective of these studies was to compare the rate and extent of
      absorption of d,l-threo-methylphenidate (MPH) from two extended-release products-
      a capsule formulation containing coated beads and an OROS tablet formulation--in
      healthy male and female subjects under fasted conditions. MATERIALS: Metadate CD
      (methylphenidate HCl, USP) Extended-Release Capsules and Concerta
      (methylphenidate hydrochloride) Extended-Release Tablets. METHODS: Two studies
      were conducted: (1) A single dose, randomized, two-way crossover study in 36
      adults comparing a 20 mg capsule and an 18 mg tablet, and (2) a single dose,
      randomized, four-way crossover study in 24 adults comparing 2 x 20 mg capsules,
      one 36 mg tablet, 3 x 20 mg capsules and one 54 mg tablet. Blood samples were
      collected over 24 hours and MPH plasma concentrations were used to calculate
      pharmacokinetic parameters for each treatment. Equivalence of pharmacokinetic
      parameters for comparable doses of the formulations was concluded if the 90%
      confidence intervals (CI) for the ratio between test and reference means were
      within the 80-125% equivalence criterion. RESULTS: Both formulations exhibited
      biphasic plasma concentration-time profiles and were equivalent in terms of total
      exposure (AUC(0-last) and AUC(0-infinity)). However, early exposure (AUC(0-4) and
      AUC(0-6), the first maximum measured plasma concentration (C(max-1), and early
      plasma MPH concentrations (1.5, 3 and 4 hours) were greater with the capsule
      formulation, while later plasma MPH concentrations (8, 10 and 12 hours) were
      greater with the tablet formulation (the CIs were outside the 80-125% required
      for equivalence and p < 0.001 for all). Similar results were obtained whether or
      not the data were normalized for the difference in total dose. CONCLUSIONS: The
      two formulations are not bioequivalent. The capsule fonnulation produces greater
      exposure to MPH and higher MPH concentrations during the first 6 hours following
      dosing. MPH is frequently used in school children, and this period would
      correspond to a major part of the school day.

PMID- 11996213
TI  - Biosensors.

PMID- 11996214
TI  - Some new aspects in biosensors.
AB  - This paper reviews recent advances in biosensors contributed mainly by our
      laboratory. The biosensors, based on the new immobilization materials - sol-gel
      organic-inorganic hybrid materials, cryohydrogel (or organohydrogel) and bilayer
      lipid membranes, are presented. The analytical performances of the biosensors are
      discussed. Applications of the biosensors in extreme environment are emphasized.
      A new generation of biosensors - surface plasmon resonance biosensors and
      capacitance biosensors, are also described.

PMID- 11996215
TI  - Functional biosensor systems via surface-nanoengineering of electronic elements.
AB  - Bioelectronics is a progressing interdisciplinary research field that involves
      the integration of biomaterials with electronic transducers such as electrodes,
      field-effect transistors or piezoelectric crystals. Surface engineering of
      biomaterials such as enzymes, antigen-antibodies or DNA on the electronic
      supports controls the electrical properties of the biomaterial/transducer
      interface and enables the electronic transduction of biorecognition events, or
      biocatalyzed transformation, on the transducers. The development of biosensor
      systems of tailored sensitivities and specificities represents a major advance in
      bioelectronics.

PMID- 11996216
TI  - Assay and screening methods for bioactive substances based on cellular signaling
      pathways.
AB  - Assay and screening methods for bioactive substances based on cellular signaling
      pathways are presented. Examples include: (1) intracellular protein
      phosphorylation and protein-protein interaction, (1-i) a new assay method for
      evaluating chemical selectivity of agonists for insulin signaling pathways based
      on agonist-induced phosphorylation of a target peptide, (1-ii) an SPR-based
      screening method for agonist selectivity for insulin signaling pathways based on
      the binding of phosphotyrosine to its specific binding protein, (1-iii) a
      fluorescent indicator for tyrosine phosphorylation-based insulin signaling
      pathways, and (1-iv) split luciferase as an optical probe for detecting protein
      protein interactions in mammalian cells based on protein splicing; (2) a
      screening method for antigen-specific IgE using mast cells based on intracellular
      calcium signaling; (3) a screening method for substrates of multidrug resistance
      associated protein (MRP); and (4) fluorescent indicators for cyclic GMP based on
      cyclic GMP-dependent protein kinase Ialpha and green fluorescent proteins.

PMID- 11996217
TI  - Electrocatalytic oxidation of NAD(P) H at mediator-modified electrodes.
AB  - A review is presented dealing with electrocatalytic NADH oxidation at mediator
      modified electrodes, summarising the history of the topic, as well as the present
      state of the art.

PMID- 11996218
TI  - Protein modified- and membrane electrodes: strategies for the development of
      biomolecular sensors.
AB  - Different procedures used for constructing protein/enzyme-modified electrodes are
      examined, in particular adsorption, covalent attachment and film deposition. The
      performances of such modified electrodes with electroactive proteins or enzymes
      attached to their active surface are examined, especially in the case of c-type
      cytochromes, hydrogenases and glucose oxidase. Another strategy presented in this
      review consists of the use of membrane electrodes with an electroactive protein
      imprisoned between a dialysis membrane and the electrode surface. The versatility
      and other advantages of such a procedure are underlined. Applications of membrane
      electrodes to the bioremediation of soils and effluents and as models for
      investigating interactions between proteins and soils are described.

PMID- 11996219
TI  - Bioelectrocatalysis by redox enzymes at modified electrodes.
AB  - Self-assembled monolayers of thiolated compounds are used as promoters for
      protein-electrode reactions. They provide an anchor group based on thiol
      chemisorptions and also a functional group for effective interaction with the
      protein. These interactions are often governed by electrostatic attraction. For
      example, for positively charged proteins, such as cytochrome c and the
      selenoprotein glutathione peroxidase, mercaptoalkanoic acids have been used. Clay
      modification of the electrode surface has been found to facilitate the
      heterogeneous electron transfer process for heme proteins, e.g. cytochrome c,
      cytochrome P450 and myoglobin. Interestingly, nucleic acids at carbon electrodes
      and thiol-modified double stranded oligonucleotides act as promoters of the redox
      communication to proteins, whereas the mechanism is still subject to controversy
      interpretations. By interacting the protein immobilised at the electrode with
      species in solution, signal chains have been constructed. The interaction can
      result in a simple co-ordination or redox reaction, depending on the nature of
      the reaction partners. For analytical purposes, e.g. biosensors, the
      electrochemical redox conversion of the immobilised protein is evaluated.

PMID- 11996220
TI  - Amperometric enzyme biosensors based on optimised electron-transfer pathways and
      non-manual immobilisation procedures.
AB  - Development of reagentless biosensors implies the tight and functional
      immobilisation of biological recognition elements on transducer surfaces.
      Specifically, in the case of amperometric enzyme electrodes, electron-transfer
      pathways between the immobilised redox protein and the electrode surface have to
      be established allowing a fast electron transfer concomitantly avoiding free
      diffusing redox species. Based on the specific nature of different redox proteins
      and non-manual immobilisation procedures possible biosensor designs are
      discussed, namely biosensors based on (i) direct electron transfer between redox
      proteins and electrodes modified with self-assembled monolayers; (ii) anisotropic
      orientation of redox proteins at monolayer-modified electrodes; (iii) electron
      transfer cascades via redox hydrogels; and (iv) electron-transfer via conducting
      polymers.

PMID- 11996221
TI  - Sensor-based measurements of the role and interactions of free radicals in
      cellular systems.
AB  - Direct real-time electrochemical measurements have offered new insight into the
      importance of free radical interplay in a number of cell culture and in vivo
      models of neurodegenerative processes. This review highlights investigations
      carried out in this laboratory of real-time superoxide and nitric oxide free
      radical generation, and presents evidence of complex inter-relationships between
      these species. These include: a novel function for astrocytic nitric oxide
      synthase in controlling neuronal nitric oxide availability; and the demonstration
      that extracellular superoxide flux can lead to the generation of NO by glial
      cells. The possible consequences of these interactions are discussed.

PMID- 11996222
TI  - Low-temperature brewing by freeze-dried immobilized cells.
AB  - We propose a novel biocatalyst in brewing. A cryotolerant strain of Saccharomyces
      cerevisiae was immobilized on delignified cellulosic material followed by freeze
      drying of the immobilized cells without the use of any cryoprotectant. The freeze
      dried immobilized biocatalyst was used in repeated-batch fermentation of wort and
      showed reduced fermentation time and increased productivities as compared with
      free freeze-dried cells (FFDCs). It also demonstrated suitability for low
      temperature brewing (5 and 0 degrees C). The fermentation time in repeated-batch
      fermentations at 15 degrees C was 1.5-2 d for a period of 13 mo, showing a high
      operational stability of the system. At 0 degrees C the freeze-dried immobilized
      biocatalyst showed a 2- to 3.5-fold decrease in fermentation time in comparison
      with FFDCs. Polyphenol contents, bitterness, and diacetyl concentration were
      lower in beers produced by freeze-dried immobilized cells as compared with FFDCs.
      At 0 degrees C polyphenols were 40% lower than at 15 degrees C. Higher alcohols
      were reduced and ethyl acetate increased in comparison with FFDCs. Amyl alcohols
      at 0 degrees C were lower than half of their content at 15 degrees C, while ethyl
      acetate was 31 mg/L at 0 degrees C and 18 mg/L at 15 degrees C. These data
      justify the improved aroma and taste of beers produced by freeze-dried
      immobilized biocatalyst mainly at low temperatures.

PMID- 11996223
TI  - Characterization of a keratinolytic metalloprotease from Bacillus sp. SCB-3.
AB  - A keratinolytic protease-producing microorganism was isolated from soybean paste
      waste and was identified as a strain of Bacillus sp. The keratinase was purified
      by polyethylene glycol precipitation and two successive column chromatographies
      with DEAE-Toyopearl 650C and Sephacryl S-200 HR. The purified enzyme had overall
      11 purification folds with an 18% yield. The results of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and gel filtration on Sephacryl G-200
      indicated that the purified enzyme was monomeric and had a molecular weight of
      134 kDa. The optimum temperature and pH were 40 degrees C and 7.0, respectively.
      This enzyme was completely inhibited by EDTA and EGTA, and it was restored by the
      addition of Ca2+ and Mg2+. These results suggested that it is a metalloprotease.
      The stimulated enzyme activity by reducing agents indicated that the reducing
      condition was important in the expression of the activity.

PMID- 11996224
TI  - Overexpression in Catharanthus roseus hairy roots of a truncated hamster 3
      hydroxy-3-methylglutaryl-CoA reductase gene.
AB  - Catharanthus roseus (L.) G. Don hairy roots harboring hamster 3-hydroxy-3
      methylglutaryl-CoA reductase (HMGR) (EC 1.1.1.88) cDNA without membrane-binding
      domain were evaluated by quantifying the levels of sterols and some indol
      alkaloids. Clone 236, with the highest hybridization signal, had the lowest
      soluble and microsomal HMGR activity and produced more ajmalicine and
      catharanthine than the control but had reduced campesterol concentration. Clone
      19, with low hybridization signal, had high soluble HMGR activity and produced
      high levels of campesterol and five to seven times more serpentine than the
      control but a low level of ajmalicine and no accumulation of catharanthine. These
      results suggest a possible role for HMGR in indole alkaloid biosynthesis and a
      possible cosuppression of both the endogenous and foreign HMGR genes in clone
      236.

PMID- 11996225
TI  - Use of glucose feeding to produce concentrated yeast cells.
AB  - A defined medium and fed-batch feeding process for the production of a yeast
      biocatalyst, developed at the 23-L scale, was scaled up to the 600-L pilot scale.
      Presterilized 100-L-vol plastic bags were implemented for the pilot-scale
      nutrient feeding. Medium of increased concentration Oqs implemented at the pilot
      scale, and equivalent dry cell weights were reached with a medium 80% more
      concentrated than that used at the laboratory scale. The higher medium
      concentration was believed to be necessary at the pilot scale owing to the
      additional heat stresses on key components (e.g., complexing of magnesium sulfate
      with phosphate), increased dilution during sterilization, lower evaporation rate
      owing to the lower vessel volume per minute air flow rate, and increased dilution
      owing to nutrient feeding or shot additions. Peak cell density was found to be
      somewhat insensitive to variations in residual glucose levels. These results
      suggest that defined medium developed at the laboratory scale may need to be
      further optimized at the pilot scale for equivalent performance.

PMID- 11996226
TI  - Adsorptive immobilization of intestinal brush border membrane on Triton X-100
      substituted Sepharose 4B.
AB  - Triton X-100-substituted Sepharose 4B (Sepharose-TX) was used for adsorptive
      immobilization of intestinal brush border membrane using lactose-phlorizin
      hydrolase as a representative membrane enzyme. Limited heating of membrane
      preparations was found to enhance binding. This enhancement is concluded to be
      owing to a greater availability of the hydrophobic sites, as also confirmed by
      the 1-anilino-8-naphthalene sulfonate fluorescence studies, for interaction with
      Triton X-100 moieties on the support. The immobilized preparations obtained by
      this procedure were found useful in hydrolysis of lactose, involving lactose
      phlorizin hydrolase, in continuous operations. It is suggested that the approach
      may be of general utility for immobilization of biologic membranes by interaction
      of their extramembrane structures using supports with appropriate hydrophobic
      groups.

PMID- 11996227
TI  - Fenton's reagent-mediated degradation of residual Kraft black liquor.
AB  - In this work, the effect of Fenton's reagent on the degradation of residual Kraft
      black liquor was investigated. The effect of Fenton's reagent on the black liquor
      degradation was dependent on the concentration of H2O2. At low concentrations (5
      and 15 mM) of H2O2, Fenton's reagent caused the degradation of phenolic groups
      (6.8 and 44.8%, respectively), the reduction of reaction medium pH (18.2%), and
      the polymerization of black liquor lignin. At a high concentration (60 mM) of
      H2O2, Fenton's reagent induced an extensive degradation of lignin (95-100%) and
      discoloration of the black liquor. In the presence of traces of iron, the
      addition of H2O2 alone induced mainly lignin fragmentation. In conclusion,
      Fenton's reagent and H2O2 alone can degrade residual Kraft black liquor under
      acidic conditions at room temperature.

PMID- 11996228
TI  - Abdominal wall hernias: a cross-sectional pictorial review.
AB  - The classification of abdominal wall hernias is often made difficult by confusing
      eponymous and anatomic nomenclature. In this article, we review the anatomy that
      defines the various types of hernias. The specific cross-sectional radiologic
      features required to correctly identify each type are then emphasized. The
      appropriate clinical context and the merits of the various imaging techniques
      available for the investigation of abdominal wall hernias are also discussed.

PMID- 11996229
TI  - Inguinal hernias: MRI and ultrasound.
AB  - This article presents an overview of the key anatomic structures of the groin
      region as seen on gross anatomy and the appearance of these structures on
      ultrasound and magnetic resonance imaging (MRI). An overview of the sonographic
      and MRI techniques used in preoperative diagnosis of inguinal hernias is
      provided, and their value is discussed. Finally, the role of ultrasound and MRI
      after surgical inguinal hernia repair is addressed.

PMID- 11996230
TI  - Internal hernia: an increasingly common cause of small bowel obstruction.
AB  - Internal hernia is an uncommon cause of small bowel obstruction that may be
      increasing in frequency. Because the clinical diagnosis of internal hernia is
      difficult, imaging studies such as computed tomography (CT) and small bowel
      follow through play an important role. Transmesenteric hernia is the most common
      type and is usually related to prior abdominal surgery, especially with creation
      of a Roux-en-Y anastomosis (eg, liver transplantation, gastric bypass). CT may
      allow confident diagnosis in most cases. In this article, we review the clinical
      and imaging findings of internal hernia based on our experience with 54 cases of
      surgically proven internal hernias including 45 transmesenteric, 6 paraduodenal,
      and 3 omental hernias, 39 of which had imaging studies available for review.

PMID- 11996231
TI  - Imaging of traumatic diaphragmatic injuries.
AB  - Traumatic diaphragmatic injury (TDI) occurs in approximately 6% of patients after
      major blunt trauma to the abdomen. Detection of such injuries is often
      problematic because of nonspecific clinical signs and the presence of additional
      intra-abdominal injuries. As the use of nonsurgical management to treat solid
      organ injuries increases, helical computed tomography (CT) must play a much
      greater role in the detection of intra-abdominal injuries. Therefore, it is
      crucial that diaphragmatic injuries are not overlooked, as fewer will be
      diagnosed at exploratory laparotomy. This article reviews the recent advances in
      helical CT that are helpful in diagnosing TDI and addresses the selected
      application of magnetic resonance imaging.

PMID- 11996232
TI  - Preoperative diagnosis of obturator hernia by computed tomography.
AB  - A retrospective study of 6 patients with obturator hernia diagnosed before
      surgery by X-ray and computed tomography (CT) was conducted between 1993 and
      2000. The initial CT of the abdomen including the pelvic area revealed
      incarcerated bowel in the obturator foramen of all 6 patients. All patients
      underwent laparotomy as soon as possible after CT scans were obtained. Resection
      of the small bowel was performed in 3 patients, and release of the small bowel
      was performed in the remaining 3 patients. There were no perioperative deaths. In
      elderly women who show evidence of small bowel obstruction by abdominal plain x
      ray studies, we recommend performing CT scans of the abdomen including the pelvic
      area for detection of obturator hernia.

PMID- 11996233
TI  - Pediatric hernias.
AB  - Indirect inguinal hernias, hydroceles, and umbilical hernias are extremely common
      in infancy and childhood. Less commonly encountered are femoral, direct inguinal,
      epigastric, and Spigelian hernias. Patient history and physical examination are
      usually sufficient for the diagnosis of a hernia. If the diagnosis is uncertain,
      ultrasound examination or herniograms are occasionally employed. Magnetic
      resonance imaging may be useful in diagnosing abdominal wall hernias in obese
      patients for whom physical examination is difficult.

PMID- 11996234
TI  - Aortic valve sparing operations.

PMID- 11996235
TI  - The renegade fact.

PMID- 11996236
TI  - A different kind of "total artificial heart": the interactive, computer-based
      human heart model.

PMID- 11996237
TI  - Results of surgical treatment of adenocarcinoma of the gastric cardia.
AB  - BACKGROUND: Comparison among different studies regarding adenocarcinoma of the
      cardia has been difficult since the Siewert classification was introduced. This
      study analyzed the experience of a single institution in the treatment of gastric
      cardia cancer with the aim of assessing principal prognostic factors and long
      term outcome. METHODS: The results of 96 patients who underwent resection with
      curative intent for gastric cardia cancer at the First Division of General
      Surgery, University of Verona, from January 1988 to February 2000, were analyzed
      statistically with special reference to Siewert type. RESULTS: Despite a high
      number of curative resections (85.4%), the 5-year survival rate was poor (24%)
      for all Siewert types (p = 0.8), and for early tumors (51%) also. Chance of cure
      was limited to pN0 and pN1 patients. Multivariate analysis showed that
      microscopic or macroscopic residual tumor and pN-positive categories had a
      significantly higher risk of death (risk ratio, 2.18 and 2.68, respectively) and
      the pN2 and pN3 category had the most negative prognostic factor (risk ratio,
      7.6). CONCLUSIONS: The long-term prognosis for gastric cardia cancer remains poor
      and is independent of Siewert type, with cure limited to pN0 and pN1 patients.

PMID- 11996238
TI  - Ischemia-reperfusion injury after lung transplantation increases risk of late
      bronchiolitis obliterans syndrome.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the most common cause of
      long-term morbidity and mortality after lung transplantation. Our hypothesis was
      that early ischemia-reperfusion injury after lung transplantation increases the
      risk of BOS. METHODS: Data on 134 patients who had lung transplantation between
      January 1, 1990 and January 1, 2000, was used for univariate and multivariate
      logistic regression analysis. RESULTS: After lung transplantation, 115 patients
      (115 of 134, 86%) survived more than 3 months. In that group, 41 patients
      developed BOS, of which 23 had progressive disease. Univariate analysis revealed
      that ischemia-reperfusion injury (p = 0.017) and two or more acute rejection
      episodes (p = 0.032) were predictors of BOS onset, whereas ischemia-reperfusion
      injury (p = 0.011) and cytomegalovirus infection (p = 0.009) predicted
      progressive BOS. Multivariate logistic regression analysis showed that ischemia
      reperfusion injury was an independent predictor for both BOS development and BOS
      progression. Two or more acute rejection episodes were also an independent
      predictor of BOS development, whereas cytomegalovirus infection was an
      independent predictor of progressive BOS. CONCLUSIONS: Ischemia-reperfusion
      injury increases the risk of BOS after lung transplantation.

PMID- 11996239
TI  - Pulmonary large cell carcinomas with neuroendocrine features are high-grade
      neuroendocrine tumors.
AB  - BACKGROUND: In 1999, the World Health Organization (WHO) categorized large cell
      carcinoma with neuroendocrine features as variants of large cell carcinoma and
      reclassified neuroendocrine lung tumors, especially typical and atypical
      carcinoid tumors. However, to date, the clinical relationship between these
      categories of neuroendocrine lung tumors has not been clearly defined. METHODS:
      We analyzed 133 cases of neuroendocrine tumors from primary lung carcinoma cases
      surgically resected. Using electron microscopy and immunohistochemical staining,
      we classified these cases as typical carcinoid (TC), atypical carcinoid (AC),
      large cell carcinoma with neuroendocrine features (LCNF), or small cell lung
      carcinoma (SCLC) based upon the WHO classification. RESULTS: TC and AC tumors
      were not related to smoking (p < 0.001) and, unlike LCNF, were found in younger
      patients (p < 0.001) without a male predominance (p < 0.001). Multivariate
      analysis revealed that LCNF predicted poorer overall and disease-free survivals
      comparable with SCLC (overall survival, p = 0.019, hazards ratio, 6.34; disease
      free survival, p = 0.007, hazards ratio, 8.19). CONCLUSIONS: The prognoses of
      LCNF are comparable with those of SCLC, and LCNF should be classified as high
      grade neuroendocrine tumors.

PMID- 11996240
TI  - Prospective study of extended segmentectomy for small lung tumors: the final
      report.
AB  - BACKGROUND: Minimal resection of small lung tumors is still controversial. This
      study was conducted to clarify whether this type of operation is acceptable.
      METHODS: From January 1992 to December 1994, 73 patients were registered in a
      multiinstitutional trial of limited resection for peripheral lung tumors less
      than 2 cm in diameter. The operative procedure consisted of extended
      segmentectomy in which the cut line of the lung was beyond the burdened segment,
      confirming N0 disease by intraoperative lymph node examination of frozen
      sections. The operation was changed to other procedures if the report was
      positive. RESULTS: All the patients were observed more than 5 years. There were
      no perioperative deaths and no major complications. A total of 55 patients were
      finally enrolled in this study. Ten patients died postoperatively, 4 of lung
      cancer and the remaining 6 died of other diseases, with no signs of recurrence.
      The 5-year survival rate, excluding these 6 patients, was 91.8%; for all patients
      including those who died it was 81.8%. A total of 18 patients were not included
      in this study for various reasons. The decrease in forced vital capacity was
      11.3% +/- 9.8% compared with the preoperative value. CONCLUSIONS: Extended
      segmentectomy is an alternative method as a standard operation for patients with
      small peripheral lung tumors, and the loss of lung function is minimal. However,
      patient selection must be strict, with intraoperative pathologic examination, and
      a wide margin to the lesion beyond the burdened segment is mandatory.

PMID- 11996241
TI  - Clinical significance of nm23 expression in resected pathologic-stage I, non
      small cell lung cancer.
AB  - BACKGROUND: Clinical significance of the status of nm23 gene, originally
      identified as an antimetastatic gene, in non-small cell lung cancer remains
      unestablished, whereas many clinical studies have demonstrated that reduced nm23
      expression is correlated with tumor progression and poor prognosis in a variety
      of malignant tumors such as breast carcinoma. METHODS: nm23 expression was
      examined immunohistochemically in a total of 117 patients with completely
      resected pathologic stage I non-small cell lung cancer. RESULTS: nm23 expression
      was positive in 73 (62.4%) patients, and there was no correlation between nm23
      expression and age, sex, performance status, pathologic T factor, histologic
      type, or degree of cancer cell differentiation. The 5-year survival rates of nm23
      positive and nm23-negative patients were 79.7% and 57.8%, respectively,
      demonstrating a significantly poorer prognosis in nm23-negative patients (p =
      0.013), which was confirmed by a multivariate analysis. nm23 was not correlated
      with the incidence of apoptosis, proliferative activity, or p53 status.
      CONCLUSIONS: nm23 expression was a significant factor for predicting a favorable
      prognosis, suggesting antimetastatic potential of the nm23 gene in non-small cell
      lung cancer.

PMID- 11996242
TI  - Stage I non-small cell lung cancer: a pragmatic approach to prognosis after
      complete resection.
AB  - BACKGROUND: Long-term results of the surgical treatment of stage I non-small cell
      lung cancer (NSCLC) are disappointing. METHODS: Univariate and multivariate
      analyses were conducted on 515 consecutive lung resections for stage I NSCLC
      performed from 1990 to 1999 and identified by reviewing a database into which
      data were entered prospectively. Tumors were staged as stages IA (n = 147) and IB
      (n = 348) according to the 1997 UICC (Union Internationale Contre le Cancer) pTNM
      classification. RESULTS: Operative mortality rates were 6.2%, 5.3%, 2.3%, and 0%
      for pneumonectomy, bilobectomy, lobectomy, and lesser resections, respectively.
      Overall survival rate was 61.1% (55.8% to 66.5%) at 5 years. Univariate analysis
      identified three significant adverse prognosticators: arteriosclerosis as
      comorbidity, pathologic T2 status, and blood vessel invasion. Male sex (p =
      0.056) and performance of pneumonectomy (p = 0.057) were at the threshold of
      statistical significance. At multivariate analysis, three independent
      prognosticators entered the model: arteriosclerosis, blood vessels invasion, and
      performance of pneumonectomy. CONCLUSIONS: Long-term survival of patients with
      completely resected stage I NSCLC was adversely influenced in a relatively
      balanced way by factors related to the clinical status of the patient, to the
      tumor, and to the treatment.

PMID- 11996243
TI  - Results of wedge resection for focal bronchioloalveolar carcinoma showing pure
      ground-glass attenuation on computed tomography.
AB  - BACKGROUND: Focal bronchioloalveolar carcinoma (BAC) showing pure ground-glass
      attenuation (GGA) on thin-section computed tomography (CT), which is considered
      to be an early-stage adenocarcinoma, has been diagnosed with increasing frequency
      due to the development and spread of the helical CT scanner. We discussed the
      appropriateness of limited resection for this type of lesion. METHODS: Between
      July 1996 and June 2001, 17 patients with localized BAC showing "pure GGA" (GGA
      without central scar formation) on thin-section CT underwent limited pulmonary
      resections. The mean patient age was 57.2 +/- 10.5 years old. Among these
      patients, four tumors were detected in a CT mass-screening program and the others
      were incidentally detected on CT during follow-up for other diseases. Fourteen
      patients underwent thoracoscopic wedge resection, and 3 underwent segmentectomy
      because of tumor location. RESULTS: The mean tumor diameter was 7.9 +/- 1.9 mm.
      On pathological examination, all tumors showed a pure bronchioloalveolar growth
      pattern and no evidence of stromal, vascular, or pleural invasion. The median
      follow-up time was 32.0 months, with no cancer death or relapse to date.
      CONCLUSIONS: Focal BAC showing pure GGA on thin-section CT is peripheral in situ
      adenocarcinoma. Wedge resection by VATS is considered to be an appropriate
      treatment for this type of lung cancer. It can be a minimally invasive complete
      resection for this type of early cancer, and offer the best chance for long-term
      survival and good quality of life.

PMID- 11996244
TI  - Primary thymic carcinoma.
AB  - BACKGROUND: Thymic carcinoma is a malignancy of the anterior mediastinum, always
      with poor prognosis. Up to the present, very few articles have discussed and
      evaluated either the clinical or pathologic features or treatments of this tumor.
      Therefore, we are in a position to analyze our research data to support our
      belief as follows. METHODS: From January 1977 until December 1997, we received
      614 patients who were diagnosed with anterior mediastinal tumors. Of the 614
      patients, 38 patients (6.2%) were diagnosed with thymic carcinoma, including 26
      men and 12 women. Data were collected from clinical records and personal
      interviews with the patients. Classification of these patients' tumor stages was
      based on the Masaoka staging system. RESULTS: We proceeded with surgery for 15 of
      the 38 patients to remove their tumors. Complete resection was done in 8 of these
      15 patients (21.0%), whereas debulking was done in the other 7 (18.4%) patients.
      The mean survival time of all the patients in this study (excluding 3 patients
      who were lost to follow-up) was 53.0 months, with a median of 24.1 months. The
      overall cumulative survival rate was 38.6% at 3 years and 27.5% at 5 years. The
      data in this research show that tumor grading (p = 0.01), resectability (p =
      0.02), and stage (p = 0.04) have statistically significant influence on patients'
      survival. CONCLUSIONS: The grade, stage, and resectability of the tumor are
      decisive factors of the effectiveness of either surgery or chemo/radiotherapies
      in the treatment of thymic carcinoma.

PMID- 11996245
TI  - Long-term results after pulmonary resection of renal cell carcinoma metastases.
AB  - BACKGROUND: Until now no conclusive data exist regarding the factors influencing
      long-term survival after pulmonary resection of renal cell carcinoma metastases.
      The aim of the present study, therefore, was to discover definitive prognostic
      factors for survival using a large and homogeneous single center patient cohort.
      METHODS: Between 1980 and 2000, 105 patients, after curative resection of lung
      metastases from renal cell carcinoma, were followed in this long-term study.
      These patients underwent a total of 150 surgical procedures. Survival analysis
      was done using the Kaplan-Meier method and the log-rank test. Multivariate
      analysis of prognostic factors was performed using the Cox multivariate
      proportional hazard model. RESULTS: Median survival after curative resection
      reached 43 months (range, 1 to 218 months). Survival at 3, 5, and 10 years was
      54%, 40%, and 33%, respectively. Univariate analysis revealed that a complete
      resection, a less than 4-cm diameter of the metastases and tumor-free lymph nodes
      at the time of primary operation, were highly significant dependent prognostic
      factors (p < 0.001). These factors were also shown to be independent prognostic
      factors as suggested by multivariate analysis (p < 0.05). CONCLUSIONS: The size
      of the metastatic nodule, the completeness of pulmonary resection, and the lymph
      node status at the time of nephrectomy are the most important prognostic factors
      that influence survival after resection of pulmonary metastases. Recurrence of
      resectable pulmonary metastases does not impair survival, thus favoring repeated
      resection in patients with recurrent disease.

PMID- 11996246
TI  - Conservative management of thoracobiliary fistula.
AB  - BACKGROUND: Thoracobiliary fistulas are rare manifestations of biliary
      disruption. Given their rarity it is not surprising that there is little
      consensus on the optimal management of thoracobiliary fistulas. METHODS: Patients
      presenting with thoracobiliary fistulas over a 5-year period (1996 to 2001) were
      evaluated. Initial management was conservative with tube thoracostomy or drainage
      of sepsis when appropriate, or both; antibiotics and somatostatin were routinely
      administered. Endoscopic retrograde cholangiography was performed when symptoms
      persisted to delineate the thoracobiliary communication and undertake
      sphincteroplasty. RESULTS: Eight patients with a mean age of 31.9 years (range 15
      to 42) were evaluated. Biliary effusion occurred in 3 patients after hepatic
      injury (n = 2) and percutaneous transhepatic cholangiography (n = 1). Bilioptysis
      occurred in 5 patients after hepatic abscess (n = 4) and hepatic injury (n = 1)
      The biliary effusion (n = 3) was successfully managed by endoscopic
      sphincterotomy in 2 patients; the third patient underwent urgent surgical biliary
      drainage. Bilioptysis (n = 5) was successfully managed in 3 patients; persistence
      of symptoms in 2 patients prompted surgical intervention. CONCLUSIONS:
      Thoracobiliary fistulas may be successfully managed using a conservative
      approach. Surgery should be reserved for persistence of symptoms after exhaustion
      of this approach.

PMID- 11996247
TI  - Transplant immunosuppression enhances efficiency of adenoviral-mediated gene
      retransfection: inhibition of interferon-gamma and immunoglobin G.
AB  - BACKGROUND: Transplant immunosuppression regimen facilitates successful
      adenovirus-mediated gene transfection and retransfection in the rat lung. Herein,
      we investigated the effect of this strategy on circulating cytokines and
      antiadenoviral immunoglobin G antibody. METHODS: Male Lewis rats were transfected
      with 1 x 10(9) pfu/mL of E1-deleted Ad5CMVLacZ vector transtracheally. Rats were
      randomly assigned to receive daily intraperitoneal triple immunosuppression
      regimen consisting of cyclosporine (15 mg/kg per day), azathioprine (6 mg/kg per
      day), and methylprednisolone (2.5 mg/kg per day), or normal saline solution.
      Retransfection was performed 35 days later to all nonimmunosuppressed animals,
      whereas immunosuppressed rats were further randomized to receive retransfection
      or phosphate-buffered saline. Animals were sacrificed on days 1, 2, 7, 35, 42,
      and 49 after the initial transfection. Beta-galactosidase activity was measured
      on lung homogenates. Interferon-gamma, tumor necrosis factor-alpha, and
      antiadenoviral immunoglobin G were measured from the serum. RESULTS: Enhanced and
      prolonged transgene expression was observed in immunosuppressed animals,
      especially after retransfection. Concentrations of serum tumor necrosis factor
      alpha in both groups were less than 12 pg/mL throughout the study. A significant
      increase in serum interferon-gamma levels was observed in nonimmunosuppressed
      animals after retransfection; this was not seen in the immunosuppressed animals.
      Serum antiadenoviral immunoglobin G titers in both groups were sharply elevated
      on day 1, and declined to basal levels by day 7, reflecting a preexisting level
      of humoral immunity to adenovirus. The titer in nonimmunosuppressed rats was
      significantly increased after retransfection, but remained at very low level in
      immunosuppressed animals. CONCLUSIONS: Inhibition of interferon-gamma and
      antiadenoviral immunoglobin G production by triple immunosuppressants may be part
      of the mechanisms that lead to enhanced and prolonged transgene expression after
      retransfection.

PMID- 11996248
TI  - Frequency of transmission of human parvovirus B19 infection by fibrin sealant
      used during thoracic surgery.
AB  - BACKGROUND: Fibrin sealant is used in many kinds of surgical procedures. Although
      pasteurization is insufficient to remove human parvovirus (HPV) B19 from this
      plasma-derived product, the frequency of HPV B19 infection transmitted by its use
      has never been known. METHODS: Blood samples of 85 patients more than 20 years of
      age who had undergone pulmonary resection with fibrin sealant were obtained
      before and 12, 24, and 48 weeks after surgery. Anti-HPV B19 antibody IgG (HPV B19
      IgG) and HPV B19 DNA were detected with these samples. RESULTS: In 56 (65.9%) of
      85 patients, blood samples obtained before operation were positive for HPV B19
      IgG. In these 56 patients, blood samples obtained 12 to 48 weeks after surgery
      were all negative for HPV B19 DNA by polymerase chain reaction (PCR). In 6
      (20.7%) of 29 patients whose blood samples were negative for HPV B19 IgG before
      surgery, blood samples obtained 12 to 48 weeks after surgery were positive for
      HPV B19 DNA by PCR and also positive for HPV B19 IgG. In 5 of these 6 patients
      reticulocyte counts decreased to less than 10 x 10(9)/l 12 to 20 days after
      surgery. CONCLUSIONS: Epidemiologic evidence suggests that more than 20%
      uninfected persons were subsequently infected with HPV B19 by use of fibrin
      sealant during surgery.

PMID- 11996249
TI  - The effect of adhesion molecule blockade on pulmonary reperfusion injury.
AB  - BACKGROUND: Selectins are the molecules involved in the initial adhesion of the
      activated neutrophil on pulmonary endothelium. We investigated the efficacy of
      selectin blockade in a selective (monoclonal antibody RMP-1) and nonselective
      (Fucoidin) manner in pulmonary reperfusion injury. METHODS: Groups of six rat
      lungs were flushed with University of Wisconsin solution then stored at 4 degrees
      C for 4 hours. They then underwent sanguinous reperfusion for 30 minutes during
      which functional measures (gas exchange, pulmonary artery pressure, and airway
      pressure) of lung performance were made. After reperfusion we estimated their
      capillary filtration coefficient (Kfc units g/cm water/minute/g wet lung tissue)
      using a gravimetric technique. Four groups were studied: group I had no
      reperfusion, group II had 30 minutes of reperfusion, group III had infusion of 20
      mg/kg Fucoidin before reperfusion, and group IV had infusion of 20 microg/mL RMP
      1 before reperfusion. RESULTS: Reperfusion injury was found between groups I and
      II by an increase in capillary filtration coefficient (1.048 +/- 0.316 to 3.063
      +/- 0.466, p < 0.01). Groups III and IV had a significantly lower Kfc than group
      II (0.967 +/- 0.134 and 1.205 +/- 0.164, respectively, p < 0.01). There was no
      significant functional difference between groups II, III, and IV. CONCLUSIONS:
      Reperfusion-induced hyperpermeability was ameliorated by selective (RMP-1) and
      nonselective (Fucoidin) selectin blockade.

PMID- 11996250
TI  - Morbidity and mortality after extent II thoracoabdominal aortic aneurysm repair.
AB  - BACKGROUND: Surgical repair of Crawford extent II thoracoabdominal aortic
      aneurysms (TAAAs) carries substantial risk for morbidity and mortality. The
      purpose of this study was to analyze the results of a large consecutive series of
      extent II TAAA repairs and identify factors that influence morbidity and
      survival. METHODS: Of 1,415 consecutive patients who underwent TAAA operations
      over a 13-year period, 442 (31.2%) had extent II repairs. Data from a
      prospectively maintained database were analyzed to determine which factors were
      associated with death and major complications. RESULTS: The operative mortality
      was 10.0% (44 patients). Postoperative complications included
      paraplegia/paraparesis in 33 patients (7.5%), pulmonary complications in 158
      (35.7%), and renal failure in 69 (15.9%). Multivariable analysis revealed that
      renal insufficiency (odds ratio [OR] 2.6), increasing age (OR 1.1/year), and
      increasing red blood cell transfusion requirements (OR 1.1/U) were predictors for
      mortality; renal insufficiency (OR 2.8) and peptic ulcer disease (OR 9.3) were
      predictors of renal failure; and rupture (OR 6.3) was a predictor of paraplegia.
      Left heart bypass was an independent protective factor against paraplegia (OR
      0.4). CONCLUSIONS: This contemporary experience demonstrates acceptable levels of
      morbidity and mortality in this high-risk group. Left heart bypass was found to
      provide protection against paraplegia in these patients.

PMID- 11996251
TI  - Aortic root remodeling operation: how do we tailor a tube graft?
AB  - BACKGROUND: In aortic root remodeling operation, it is difficult to perform graft
      sizing and tailor a graft appropriately. Thus the aim of this study was to create
      guidelines for sizing and tailoring that would help to standardize the operation.
      METHODS: We studied the anatomy of the aortic root and assessed the reliability
      of three equations reported to assist in graft sizing with aortic root casts
      obtained from 127 cadavers. RESULTS: Yacoub's equation and ours accurately
      predicted the diameter at the sinotubular junction. Three cusps of the aortic
      valve were not equal in size. Sinus height of the aortic root was unpredictable.
      CONCLUSIONS: Based on these results, we recommend that aortic root remodeling
      operation should be performed as follows: (1) graft sizing should be performed
      using Yacoub's way or our way; (2) the tube graft should be cut into three parts
      in proportion to the size of each cusp; and (3) the position of the commissures
      in the tube graft should be secured with sutures first, and the depth of the
      sinuses should be determined later.

PMID- 11996252
TI  - Dynamic analysis of the aortic valve using a finite element model.
AB  - BACKGROUND: The major aim of this study was to examine the leaflet/aortic root
      interaction during the cardiac cycle, including the stresses developed during the
      interaction. METHODS: Dynamic finite element analysis was used along with a
      geometrically accurate model of the aortic valve and the sinuses. Shell elements
      along with proper contact conditions were also used in the model. Pressure
      patterns during the cardiac cycle were given as an input, and a linear elastic
      model was assumed for the material. RESULTS: We found that aortic root dilation
      starts before the opening of the leaflet and is substantial by the time leaflet
      opens. Dilation of the root alone helps in opening the leaflet to about 20%. The
      equivalent stress pattern shows an instantaneous increase in stress at the
      coaptation surface during closure. Stresses increase as the point of attachment
      is approached from the free surface. CONCLUSIONS: The complex interplay of the
      geometry of the valve system can be effectively analyzed using a sophisticated
      dynamic finite element model. Results not previously brought out by the earlier
      static analysis shed new light on the root/valve interaction.

PMID- 11996253
TI  - Five-year experience in aortic root replacement with the flanged composite graft.
AB  - BACKGROUND: Replacement of the aortic root with a composite graft containing a
      prosthetic mechanic valve is the preferred surgical procedure for tailoring the
      aortic root. The aim of this study is to determine the 5-year experience with the
      composite root replacement using our new modification of the Bentall technique.
      METHODS: Between January 1996 and June 2001, 96 patients underwent aortic root
      replacement using a flanged composite graft. Eighty patients (83.3%) were male,
      and 16 patients (16.7%) were female with a mean age of 48.7 +/- 14.4 years.
      Indications for operation were a true or false aneurysm (65.6%), severe calcified
      aortic valve stenosis (4.2%) or severe aortic insufficiency (2.1%) with dilated
      ascending aorta, acute dissection (2.1%), or combination of indications (26%).
      Thirty-one patients (32.3%) received a concomitant cardiac procedure. Mean aortic
      cross-clamp time was 89.5 +/- 28.6 minutes, and mean cardiopulmonary bypass time
      was 146.2 +/- 45.6 minutes. Total follow-up was 253.9 patient-years. RESULTS:
      Operative mortality was 8.3% (8 patients). The causes of hospital mortality were
      severe bleeding (3 patients), low cardiac output syndrome (2), acute respiratory
      distress syndrome (2) and cerebrovascular event (1). No patient died of flange
      related complications. Univariate predictors of early mortality were low cardiac
      output syndrome (p < 0.001), neurologic complication (p = 0.03), and renal
      complication (p = 0.03). Multivariate analysis demonstrated only low cardiac
      output syndrome to be significant (p = 0.001) predictor for early mortality.
      There were five (5.7%) late deaths. Actuarial survival was 82.65% +/- 4.8% at 5
      years (1.95% patient-year). Cox proportional hazards regression analysis
      demonstrated only low cardiac output syndrome to be significant (p = 0.032)
      predictor for late mortality. Actuarial freedom from prosthetic- and technique
      related mortality was 100% at 5 years. CONCLUSIONS: The flanged composite graft
      offers excellent long-term results, with very low prevalence of prosthetic
      related complications. The new created sinuses and the flange are especially
      helpful to continue physiologic function of the aortic root.

PMID- 11996254
TI  - Self-expandable aortic stent-grafts for treatment of descending aortic
      dissections.
AB  - BACKGROUND: Acute aortic dissection is a life-threatening medical condition that
      is associated with high morbidity and mortality. METHODS: Of 198 patients treated
      with a self-expanding polyester-covered stent-graft for various pathologic aortic
      conditions in our institution, we selected 70 consecutive patients with type B
      aortic dissection who were undergoing treatment. The stent-graft was introduced
      through the femoral artery in the angiography suite, under general anesthesia
      with systemic heparinization and induced hypotension. RESULTS: The procedure was
      performed in 70 patients; of these, 58 had descending aortic dissection and 12
      had atypical dissections. The procedure was successful in 65 patients (92.9%), as
      documented by exclusion of the false lumen of the thoracic aorta. Eleven patients
      (18.9%) had persistent blood flow in the false lumen of the abdominal aorta due
      to distal reentries. Five patients (7.1%) underwent conversion to surgery.
      Insertion of additional stent-grafts was required in 34 patients (48.6%). At 29
      months of follow-up, 91.4% of the patients were alive. CONCLUSIONS: Stent-grafts
      are an important means of treating aortic dissections, which may replace
      conventional medical treatment of this condition for the majority of patients.

PMID- 11996255
TI  - Endovascular treatment of thoracic disease: patient selection and a proposal of a
      risk score.
AB  - BACKGROUND: Although selection criteria and subgroup analysis are still in the
      early developmental stages, endovascular treatment of aortic disease has become
      an alternative to surgery for many patients. METHODS: From November 1996 to
      November 1999, 49 patients were treated with a self-expandable endoprosthesis at
      our institution. Most patients had acute aortic dissections. Thirteen of these
      patients did not follow the anatomic selection protocol. We retrospectively
      analyzed these patients to compare our numerical risk score (which includes
      clinical and anatomic criteria) between groups with or without success and
      between groups that followed the anatomic protocol (P) or did not follow the
      anatomic protocol (E [exception]). RESULTS: Success rates were similar in groups
      P and E, although mortality rates were higher in group E. Patients from group E
      had longer procedures and required multiple stents more frequently. The proposed
      risk score was able to differentiate between groups with or without success, as
      well as between groups P and E. CONCLUSIONS: In order to reduce mortality and
      morbidity rates, careful selection criteria must be followed when treating
      patients endovascularly. Although it is time-consuming, using objective criteria
      can help select patients for endovascular treatment. We propose that patients
      with a risk score higher than 11 should only undergo percutaneous treatment when
      they have an unacceptably high surgical risk, and even so only after a detailed
      discussion of the risks.

PMID- 11996256
TI  - Cold blood spinal cord plegia for prediction of spinal cord ischemia during
      thoracoabdominal aneurysm repair.
AB  - BACKGROUND: This clinical study was undertaken to evaluate changes in motor
      evoked potentials (MEPs) during cold blood infusion into a thoracoabdominal
      aortic aneurysm. We also determined the efficacy of this infusion method for
      predicting spinal cord injury during thoracoabdominal aortic aneurysmal surgery.
      METHODS: We monitored descending evoked spinal cord potentials (ESCPs), segmental
      ESCPs, and MEPs during the prosthetic replacement phase of thoracoabdominal
      aneurysmal surgery. We perfused cold blood (4 degrees C, 300 to 450 mL) into
      aneurysms after clamping the aorta, while monitoring spinal cord potentials in 6
      cases of thoracoabdominal aortic aneurysm. If the spinal cord potentials
      decreased during infusion of cold blood, we reconstructed the intercostal
      arteries in the aneurysm. If the potentials did not change during the infusion of
      cold blood and after the aneurysmectomy, we did not reconstruct the intercostal
      arteries and ligated all of them. RESULTS: Postoperative paraplegia did not occur
      in any case. The MEPs decreased in amplitude after infusion of cold blood in 3
      cases, but amplitude recovered after reconstruction of the intercostal arteries.
      The other 3 cases did not show any change after infusion of cold blood, and all
      of the intercostal arteries in the aneurysm were ligated. CONCLUSIONS: Cold blood
      infusion into the aneurysm while monitoring MEPs was a useful adjunct to detect
      the presence of critical intercostal arteries and to facilitate thoracoabdominal
      aortic aneurysmal surgery.

PMID- 11996257
TI  - Validation of a left atrial lesion pattern for intraoperative ablation of atrial
      fibrillation.
AB  - BACKGROUND: Evidence that atrial fibrillation may begin in early stages from
      triggers or reentry circuits primarily in the left atrium suggests that the
      entire Maze 3 lesion pattern may be unnecessary. In the present study we describe
      a new left atrial lesion pattern for intraoperative linear ablation of chronic
      atrial fibrillation. METHODS: Endocardial radiofrequency ablation was performed
      on 12 dogs with chronic atrial fibrillation. Lesions to isolate pulmonary veins
      in pairs, the left atrial appendage, and connecting lesions between these
      structures were administered in a randomized approach. RESULTS: Twelve dogs were
      in chronic atrial fibrillation for 31 +/- 21 days before ablation. Atrial
      fibrillation was successfully ablated and rendered noninducible in all 12 dogs.
      All treatment failures observed with less than the full lesion pattern became a
      success when the remaining lesions were given. CONCLUSIONS: Atrial fibrillation
      ablation using this left atrial lesion pattern is highly successful in this
      model. This approach may have significant utility as a concomitant procedure for
      patients with atrial fibrillation undergoing mitral valve procedures.

PMID- 11996258
TI  - Simple surgical isolation of pulmonary veins for treating secondary atrial
      fibrillation in mitral valve disease.
AB  - BACKGROUND: Chronic atrial fibrillation (AF) due to mitral valve disease has been
      successfully treated by surgery. We performed a study to evaluate the
      effectiveness of a surgical method of simple pulmonary vein isolation (PVI)
      without radiofrequency or cryoablation in the restoration of sinus rhythm in a
      group of patients. METHODS: Fifteen patients were operated on for mitral valve
      disease and chronic AF. The technique consists basically of a circumferential
      incision excluding the pulmonary vein ostia from the left atrium. RESULTS: Sinus
      rhythm was achieved in 92.3% of the patients at 6-month follow-up.
      Echocardiograms 2 months after surgery showed a mean decrease of 1.1 cm in left
      atrial size. Effective atrial ejection was reestablished in all patients in whom
      sinus rhythm was achieved (mean LA ejection fraction 41% +/- 14%). Twenty-four
      hour Holter recordings did not show episodes of paroxysmal atrial fibrillation in
      any patients. Four patients had isolated episodes of ventricular ectopic beats.
      Stress electrocardiograms showed mean maximal ventricular response was 64% +/-
      11% and 73% +/- 9% of predicted value at 2 and 6 months, respectively. All
      patients had improved NYHA functional class after surgery; 74% of patients were
      in NYHA functional class I at 6 months compared with 13.3% preoperatively.
      CONCLUSIONS: Pulmonary vein isolation without the use of radiofrequency or
      cryoablation is effective in restoring sinus rhythm in patients with chronic AF
      secondary to mitral valve disease. Based on simple surgical incisions, this
      technique is more advantageous than others requiring additional instrumentation.

PMID- 11996259
TI  - Cerebral blood flow and cognitive dysfunction after coronary surgery.
AB  - BACKGROUND: Postoperative cognitive dysfunction after cardiac surgery has been
      attributed both to embolic events and periods with reduced cerebral perfusion. We
      investigated whether cognitive dysfunction after coronary surgery is associated
      with changes in regional cerebral blood flow (CBF) using single photon emission
      computed tomography. METHODS: Before surgery and at discharge, 15 coronary
      surgery patients were studied. Global and regional CBF were measured using a
      brain-dedicated single photon emission computed tomography scanner, and
      neuropsychological testing with seven subtests was performed. Postoperative
      cognitive dysfunction was defined as a Z score above 2. Normative single photon
      emission computed tomography data were available from 26 healthy age-matched
      controls. RESULTS: Preoperative global CBF was significantly lower in patients
      compared with controls (53.7 versus 46.1 mL/100 g/min, p = 0.006). After surgery,
      global CBF significantly decreased in the patient group (46.1 versus 38.6 mL/100
      g/min, p = 0.0001). No significant differences were detected in regional CBF.
      Cognitive dysfunction was identified in 4 of the 15 patients (26.7%, 95% CI 7.8%
      to 55.1%). No correlation was found between the neuropsychological Z score and
      global or regional CBF. CONCLUSIONS: The significant decrease in CBF after
      coronary surgery was uniformly distributed and was not correlated to
      postoperative cognitive dysfunction.

PMID- 11996260
TI  - Endoscopic internal thoracic artery dissection leads to significant reduction of
      pain after minimally invasive direct coronary artery bypass graft surgery.
AB  - BACKGROUND: The aim of this study was to evaluate postoperative pain levels after
      endoscopic versus conventional internal thoracic artery (ITA) dissection for
      minimally invasive direct coronary artery bypass graft surgery (MIDCABG) surgery.
      Results were compared with pain levels associated with conventional cardiac
      bypass operations through a median sternotomy. METHODS: Of 190 patients included
      in this prospective study, 24 patients had endoscopic ITA takedown (MIDCABG-endo)
      using the da Vinci telemanipulator followed by a manual coronary anastomosis
      through a left minithoracotomy. A conventional MIDCABG operation (MIDCABG-conv)
      was performed in 73 patients with ITA preparation under direct vision.
      Postoperative pain levels after conventional CABG through a median sternotomy
      (CABG-conv, n = 93) served as controls. A standarized questionnaire including
      visual analog scale (VAS) was used for prospective pain assessment from POD 1 to
      7. RESULTS: Pain levels (VAS) declined in all groups from POD 1 to 7. Overall
      pain levels were significantly lower in the MIDCABG-endo group as compared with
      MIDCABG-conv and CABG-conv groups, respectively (p < 0.001, general linear
      model). There was no significant difference between the MIDCABG-conv and CABG
      conv (p = not significant, general linear model) groups. Furthermore, patients
      after MIDCABG-endo required fewer nonsteroidal anti-inflammatory drugs and opioid
      medications, postoperatively. CONCLUSIONS: An endoscopic ITA takedown in MIDCABG
      surgery leads to significantly reduced postoperative pain levels possibly because
      of less rib retraction.

PMID- 11996261
TI  - Endothelin blockade potentiates endothelial protective effects of ACE inhibitors
      in saphenous veins.
AB  - BACKGROUND: Angiotensin II and endothelin-1 are potent endothelium-derived
      contracting factors. The effects of acute endothelin antagonism on endothelial
      function in saphenous vein from patients treated with and without angiotensin
      converting enzyme inhibitors were compared. METHODS: Vascular segments of
      saphenous vein were obtained perioperatively from 14 patients on angiotensin
      converting enzyme inhibitors and 29 controls. In vitro endothelium-dependent and 
      independent responses to acetylcholine and sodium nitroprusside were assessed by
      constructing isometric dose-response curves in precontracted rings in the
      presence and absence of bosentan (endothelinA/B receptor antagonist) and BQ-123
      (endothelinA antagonist) using isolated organ baths. Percent maximum relaxation
      and sensitivity were compared between interventions. RESULTS: Endothelium
      dependent relaxation to acetylcholine was augmented in the angiotensin-converting
      enzyme inhibitor-treated group (p < 0.005). Both specific and mixed endothelin
      receptor blockade improved acetylcholine-mediated relaxation in the angiotensin
      converting enzyme inhibitor-treated and untreated groups (p < 0.02). The effects
      of these antagonists were endothelium specific as endothelium-independent
      responses to sodium nitroprusside remain unaltered. CONCLUSIONS: These data
      demonstrate that (1) chronic angiotensin-converting enzyme inhibition improves
      endothelial function in saphenous veins, and (2) this effect can be further
      augmented by acute endothelin blockade. These data suggest that antagonism of
      both angiotensin II and endothelin may be important in attenuating saphenous vein
      arteriosclerosis.

PMID- 11996262
TI  - Improved patency in vein grafts harvested with surrounding tissue: results of a
      randomized study using three harvesting techniques.
AB  - BACKGROUND: The technique of harvesting the saphenous vein for coronary artery
      bypass grafting influences the fate of vein grafts. The patency rate of a novel
      "no-touch" technique in which the vein is harvested with a pedicle of surrounding
      tissue and not distended was compared with two other techniques. METHODS: One
      hundred fifty-six patients who underwent coronary artery bypass grafting were
      randomized to three saphenous vein harvesting groups: group C (conventional)--the
      vein was stripped, distended, and stored in saline; group I (intermediate)--the
      vein was stripped, local application of papaverine was used instead of
      distention, and the vessel was then stored in heparinized blood; and group NT (no
      touch)--the vein was harvested with surrounding tissue, not distended, and stored
      in heparinized blood. Surgical and clinical factors that might influence graft
      occlusion were recorded. One hundred twenty-seven vein grafts in group C, 116 in
      group I, and 124 in group NT, as well as 118 left internal mammary artery grafts,
      were angiographically assessed at 18 months mean follow-up time. RESULTS: The
      vein graft patency was 88.9% in group C, 86.2% in group I, and 95.4% in group NT.
      There was a statistically significant difference between the patency of the
      single-vein grafts in NT and the other two groups (p = 0.025). The higher the
      flow, the better the patency irrespective of the technique used. A higher
      attrition rate was found in vein segments taken from the knee area in group I.
      Poor vein quality affected patency in all groups. Forty-seven of all 51
      sequential grafts (92.2%) were patent. The patency of left internal mammary
      artery grafts was 108 of 118 (91.5%). CONCLUSIONS: We conclude that preservation
      of the surrounding tissue of the saphenous vein using this no-touch technique
      abolishes venospasm intraoperatively and plays an important role in maintaining
      vein graft function and patency.

PMID- 11996263
TI  - Elimination of cardiopulmonary bypass improves early survival for multivessel
      coronary artery bypass patients.
AB  - BACKGROUND: Coronary artery bypass graft (CABG) surgery performed without
      cardiopulmonary bypass (CPB) is currently increasing in clinical practice.
      Decreased morbidity associated with off-pump (OP) CABG in selected risk groups
      examined in relatively small, single institution groups has been the focus of
      most recent studies. The purpose of this study was to determine the independent
      impact of CPB on early survival in all isolated multivessel CABG patients
      undergoing surgery in two large institutions with established experience in
      OPCABG techniques. METHODS: A review of two large databases employed by multiple
      surgeons in the hospitals of two institutions identified 8,758 multivessel CABG
      procedures performed from January 1998 through July 2000. In all, 8,449
      procedures were included in a multivariate logistic regression analysis to
      determine the relative impact of CPB on mortality independent of known risk
      factors for mortality. Procedures were also divided into two treatment groups
      based on the use of CPB: 6,466 had CABG with CPB (CABG-CPB), 1,983 had CABG
      without CPB (OPCABG). Disparities between groups were identified by univariate
      analysis of 17 preoperative risk factors and treatment groups were compared by
      Parsonnet's risk stratification model. Finally, computer-matched groups based on
      propensity score for institution selection for OPCABG were combined and analyzed
      by a logistic regression model predicting risk for mortality. RESULTS: CABG-CPB
      was associated with increased mortality compared with OPCABG by univariate
      analysis, 3.5% versus 1.8%, despite a lower predicted risk in the CABG-CPB group.
      CPB was associated with increased mortality by multiple logistic regression
      analysis with an odds ratio of 1.79 (95% confidence interval = 1.24 to 2.67). An
      increased risk of mortality associated with CPB was also determined by logistic
      regression analysis of the combined computer-matched groups based on OPCABG
      selection propensity scores with an odds ratio of 1.9 (95% confidence interval =
      1.2 to 3.1). CONCLUSIONS: Elimination of CPB improves early survival in
      multivessel CABG patients. Rigorous attempts to statistically account for
      selection bias maintained a clear association between CPB and increased
      mortality. Larger multiinstitutional studies are needed to confirm these findings
      and determine the most appropriate application of OPCABG.

PMID- 11996264
TI  - Alveolar recruitment strategy increases arterial oxygenation during one-lung
      ventilation.
AB  - BACKGROUND: Deterioration of gas exchange during one lung ventilation (OLV) is
      caused by both total collapse of the nondependent lung and partial collapse of
      the dependent lung. A previous report demonstrated that an alveolar recruitment
      strategy (ARS) improves lung function during general anesthesia in supine
      patients. The objective of this article was to study the impact of this ARS on
      arterial oxygenation in patients undergoing OLV for lobectomies. METHODS: Ten
      patients undergoing open lobectomies were studied at three time points: (1)
      during two-lung ventilation (TLV), (2) during OLV before, and (3) after ARS. The
      ARS maneuver was done by increasing peak inspiratory pressure to 40 cm H2O,
      together with a positive end-expiratory pressure (PEEP) of 20 cm H2O for 10
      respiratory cycles. After the maneuver, ventilation parameters were returned to
      the settings before intervention. RESULTS: During OLV, PaO2 was statistically
      lower before the recruitment (data as median, first, and third quartile, 217
      [range 134 to 325] mm Hg) compared with OLV afterwards (470 [range 396 to 525] mm
      Hg) and with TLV (515 [range 442 to 532] mm Hg). After ARS, PaO2 values during
      OLV were similar to those during TLV. During OLV, the degree of pulmonary
      collapse in the nondependent lung, the hemodynamic status, and the ventilation
      parameters were similar before and after ARS. CONCLUSIONS: Alveolar recruitment
      of the dependent lung augments PaO2 values during one-lung ventilation.

PMID- 11996265
TI  - Therapeutic angiogenesis induced by local autologous bone marrow cell
      implantation.
AB  - BACKGROUND: Therapeutic angiogenesis was induced by local autologous bone marrow
      cell implantation (BMCI) in ischemic hindlimb or ischemic heart models in rats.
      This study was designed to investigate the toxicity and therapeutic potency of
      local BMCI using a chronic coronary occlusion model in dogs. METHODS: The canine
      chronic coronary occlusion model was created by ligating of the left anterior
      descending artery (LAD). The myocardium in the left ventricle was divided into
      distinct normal, marginal, and infarction areas 30 days after LAD ligation. Each
      area was injected at two locations, with either 2 x 10(7) bone marrow cells (n =
      7, BMCI group) or 0.1 mL phosphate-buffered saline (PBS) only (n = 7, PBS group),
      respectively. Hemodynamics were evaluated by a single ultrasonic transducer and
      echocardiography before and 30 days after the treatment. Angiogenesis was
      evaluated by vessel count 30 days after the treatment. The toxicity of BMCI
      treatment was also evaluated in 8 normal dogs by following changes in
      electrocardiography (ECG), echocardiography, local histology, and systemic
      biochemistry indexes. RESULTS: There was a significantly higher percentage of
      wall thickening in the marginal area in the BMCI group than in the PBS group 30
      days after treatment (14.5 +/- 2.28 versus 8.1 +/- 3.00, p = 0.002).
      Significantly more microvessels were observed in the marginal area in the BMCI
      group than in the PBS group 30 days after treatment (127.7 +/- 20.1 versus 88.0
      +/- 10.2/field, p = 0.0007). No systemic or local toxicity was found following
      BMCI treatment in the acute or chronic phases. CONCLUSIONS: BMCI treatment
      improved local wall thickening dynamics, presumably due to the angiogenesis
      induced by the treatment. This indicates that it might be a safe and effective
      therapy for ischemic heart disease.

PMID- 11996266
TI  - Disease-specific remodeling of cardiac mitochondria after a left ventricular
      assist device.
AB  - BACKGROUND: Failing hearts can exhibit elements of structural and molecular
      "reverse remodeling" after support with a left ventricular assist device (LVAD).
      The present study examined LVAD-induced remodeling of cardiac mitochondria.
      METHODS: Left ventricular tissue from 20 failing and 21 LVAD-supported hearts,
      catagorized as ischemic (ICM) or dilated (DCM) cardiomyopathy and four nonfailing
      hearts were studied. Myocyte mitochondrial ultrastructure was assessed by high
      performance liquid chromatography determination of cardiolipin, a specific lipid
      component of the inner membrane, and its three major molecular species: L4, L3O,
      and L2O2. RESULTS: Both failing and LVAD-supported hearts exhibited a reduction
      in cardiolipin content that was independent of the type of cardiomyopathy.
      However, in failing/ICM hearts, there was a 25% increase in the L4/L3O ratio and
      a 70% increase in the L4/L2O2 ratio, indicating a change in cardiolipin
      composition. These alterations were normalized by LVAD support. In sharp
      contrast, molecular species ratios in DCM hearts were the same as those in
      nonfailing hearts regardless of whether LVAD support had been used or not.
      CONCLUSIONS: These data demonstrate LVAD-induced reverse remodeling of myocyte
      cardiolipin composition in ICM but not DCM hearts.

PMID- 11996267
TI  - Comparison of the Nottingham Health Profile and the 36-item health survey
      questionnaires in cardiac surgery.
AB  - BACKGROUND: Quality of life (QOL) instruments help to integrate the patient's
      view into clinical practice and into the evaluation of new therapeutic
      strategies. The aim of the present study was to determine which of two generic
      QOL instruments, the Nottingham Health Profile (NHP) or the Short Form Health
      Survey (SF36), was the more suitable for use in cardiac surgery. METHODS: The NHP
      and the SF36 were compared before and 5 weeks after surgery. Comparison was
      conducted in two stages: (1) the acceptability and psychometric properties of the
      tools were measured, and (2) the short-time evolution of angina pectoris and
      dyspnea status were assessed with the QOL. RESULTS: A total of 322 patients were
      included and 299 patients completed preoperative and postoperative
      questionnaires. Acceptability was similar for both questionnaires. Internal
      consistency, ceiling effect, sensitivity to change, as well as the assessment of
      the evolution of angina pectoris and dyspnea were better for the SF36 than for
      the NHP. CONCLUSIONS: The SF36 seems more suitable than the NHP for evaluating
      QOL in cardiac surgery.

PMID- 11996268
TI  - Role of apoptosis in myocardial stunning after open heart surgery.
AB  - BACKGROUND: Myocardial preservation during open heart surgery is a subject of
      intense investigation. A prerequisite for further improvement is a better
      understanding of the underlying pathophysiologic mechanisms responsible for
      postoperative myocardial stunning. In this report, we analyzed the role of
      apoptosis in myocardial stunning. METHODS: Myocardial samples were obtained from
      11 patients undergoing elective coronary artery bypass grafting before (control)
      and after cardioplegic arrest and reperfusion. Specimens were examined for
      apoptosis by electron microscopy, in situ end-labeling of DNA fragments, and
      biochemically for mitochondrial cytochrome c release. RESULTS: Electron
      microscopy revealed condensation and margination of nuclear chromatin after
      surgery, as well as swelling and membrane rupture in mitochondria of single
      myocytes surrounded by healthy cells. TUNEL-positive cells were also found.
      Cytochrome c release, an initial step in apoptosis, revealed a 3.4 +/- 0.4-fold
      increase during surgery (p < 0.0001). Furthermore, cytochrome c release from
      otherwise intact mitochondria showed a negative correlation with left ventricular
      function and a positive correlation with the duration of cardioplegic arrest and
      reperfusion (p < 0.05). CONCLUSIONS: Our data demonstrate that programmed cell
      death is evident early after open heart surgery and correlates with declining
      cardiac contractility. We conclude that apoptosis may be an important mechanism
      in postoperative myocardial stunning.

PMID- 11996269
TI  - Aprikalim reduces the Na+-Ca2+ exchange outward current enhanced by hyperkalemia
      in rat ventricular myocytes.
AB  - BACKGROUND: [corrected] Aprikalim, an adenosine triphosphate (ATP) sensitive K+
      (K(ATP)) channel opener, attenuates the elevation of intracellular Ca2+
      concentration ([Ca2+]i) and improves the contractile functions after hyperkalemic
      and hypothermic cardioplegia. There is evidence that cardioplegia increases the
      Na+-Ca2+ exchange activity without affecting Ca2+ influx through L-type Ca2+
      channels or Ca2+ content in the sarcoplasmic reticulum, the intracellular Ca2+
      store. METHODS: We measured the Na+-Ca2+ exchange outward current with the patch
      clamp technique in single rat ventricular myocytes exposed to hyperkalemia and
      hypothermia in the presence of aprikalim. The intracellular calcium concentration
      ([Ca2+]i) during cardioplegia, and the contractile function and [Ca2+]i
      transients induced by electrical stimulation or caffeine during rewarming and
      reperfusion in single ventricular myocytes were also determined. Contraction and
      [Ca2+]i were determined with video tracking and spectrofluorometry, respectively.
      RESULTS: Aprikalim, 100 micromol/L, the effect of which was blocked by
      glibamclamide, a K(ATP) inhibitor, significantly attenuated the hyperkalemia
      elevated Na+-Ca2+ exchange current by 26% and 11% at 22 degrees C and 4 degrees
      C, respectively. Aprikalim also attenuated significantly the [Ca2+]i elevated
      during cardioplegia. Furthermore aprikalim significantly attenuated the reduction
      in amplitude and prolongation in duration of contraction of myocytes after
      cardioplegia. The effects of aprikalim mimicked those of nickle (Ni2+), a Na+
      Ca2+ exchange blocker. The electrically or caffeine-induced [Ca2+]i transients
      were unaltered by cardioplegia or aprikalim. CONCLUSIONS: Aprikalim attenuates
      the Na+-Ca2+ exchange outward current elevated by hyperkalemia, which may
      attenuate the [Ca2+]i elevation during hyperkalemia and improve the contractile
      function after cardioplegia in the ventricular myocyte. The study provides
      further support that addition of a K(ATP) channel opener to the cardioplegic
      solution may produce beneficial effects in open heart surgery.

PMID- 11996270
TI  - Individualized total cavopulmonary connection technique for patients with
      asplenia syndrome.
AB  - BACKGROUND: Outcomes after univentricular repair for patients with asplenia
      syndrome remain unsatisfactory, not only because of clinical difficulties in
      patient selection, but also secondary to technical difficulties in the separation
      of the systemic and pulmonary circulations, particularly with the rerouting
      technique for the inferior systemic veins. METHODS: Between February 1995 and May
      2000, a total of 14 consecutive patients with asplenia syndrome underwent
      bidirectional cavopulmonary connection with obliteration of additional pulmonary
      blood flow, followed by a total cavopulmonary connection. The rerouting technique
      for inferior systemic venous blood flow was individualized to optimize laminar
      nonturbulent flow characteristics in the pathway, and to minimize prosthetic load
      and suture load on the atrial wall. The lateral tunnel or tube conduit technique
      was used in an extraatrial, intra-extraatrial, or intraatrial fashion. No
      fenestration was applied. RESULTS: No hospital mortality was observed. Systemic
      venous flow was evaluated using magnetic resonance angiography, revealing no
      signs of obstruction, turbulence, or stasis either in or near the reconstructed
      pathways, irrespective of the rerouting technique. Postoperative catheterization
      revealed favorable hemodynamics including an inferior vena cava pressure of 13 +/
      2 mm Hg and arterial oxygen saturation of 93.4% +/- 3.5% at room air. All
      patients have remained free of symptoms, although 1 patient died of acute septic
      complications 3.5 years after the procedure. CONCLUSIONS: The complexity of
      cardiac anomalies in asplenia syndrome warrants individualization of the total
      cavopulmonary connection technique used in reconstruction of the inferior
      systemic venous pathway. Optimizing flow characteristics in the pathway should be
      a priority. A staging approach allows suitable selection of candidates for
      univentricular repair.

PMID- 11996271
TI  - Effects of autologous platelet concentrate reinfusion after open heart surgery in
      patients with congenital heart disease.
AB  - BACKGROUND: Plasma pheresis and reinfusion of platelet-rich plasma has not been
      shown to reduce blood loss in cardiac patients. Recently, freshly prepared
      autologous platelet concentrates (PC) can be made from patient's blood and has a
      higher concentration than conventional platelet rich plasma. In this study, the
      effects of autologous PC reinfusion were examined after open heart surgery in
      patients with congenital heart disease. METHODS: Eight patients with noncyanotic
      congenital heart disease, who underwent open heart surgery and reinfusion of
      autologous PC, were classified as the PC group. Eight other patients with
      noncyanotic congenital heart disease, who underwent only open heart surgery, were
      defined as the control group. Ages ranged from 2 to 24 years and were not
      significantly different between the two groups (9.3 +/- 5.1 years in the PC group
      and 12.6 +/- 7.9 years in the control group, p = 0.33). In the PC group, blood
      was collected from the femoral vein through a 6F catheter introducer; 9 to 20 U
      (13.0 +/- 5.4 U, 0.42 +/- 0.22 U/kg) of autologous PC were prepared and were
      reinfused after protamine administration. The time course of platelet counts was
      examined until postoperative day 7. Aggregation responses to adenosine
      diphosphate; (4 micromol/L and 8 micromol/L), collagen (1 micromol/L and 5
      micromol/L), and epinephrine (5 micromol/L and 10 micromol/L) were evaluated
      after induction of anesthesia (individual references), after protamine
      administration, at the end of the operation; these responses were shown as
      recovery ratios. RESULTS: Blood loss during surgery in the PC group was
      significantly less than in the control group (4.8 +/- 3.0 mL/kg versus 7.8 +/-
      1.7 mL/kg, p = 0.044). Similarly blood loss on postoperative day 1 in the PC
      group was significantly less than in the control group (3.6 +/- 1.2 mL/kg versus
      7.2 +/- 3.1 mL/kg, p = 0.013). The platelet counts in the PC group were larger
      than those in the control group until postoperative day 5, after reinfusion of
      prepared autologous PC. The recovery ratios of the aggregation responses to
      adenosine diphosphate, collagen, and epinephrine after protamine administration
      were not significantly different between the two groups. However, recovery in the
      PC group after reinfusion of the prepared autologous PC was greater than in the
      control group. CONCLUSIONS: Reinfusion of the freshly prepared autologous PC was
      followed by good aggregation responses and low blood loss in patients with
      noncyanotic congenital heart disease after open heart surgery. This procedure may
      be useful in pediatric open heart surgery without blood transfusion or with
      little administration of homologous blood products.

PMID- 11996272
TI  - Tracheal polyp.
AB  - Benign tumors of the tracheobronchial tree are extremely rare. A case of a benign
      inflammatory endotracheal polyp and literature review are presented, including
      classification and treatment options. Although rare, these lesions must be
      efficiently diagnosed and expeditiously removed to prevent airway occlusion or
      irreversible pulmonary disease.

PMID- 11996273
TI  - Videothoracoscopic splanchnicectomy for intractable pain from adrenal metastasis.
AB  - Splanchnicectomy has been known for years as a treatment for refractory pain in
      patients with pancreatic cancer or chronic pancreatitis. We report herein the
      performance of a videothoracoscopic left splanchnicectomy in a patient with a
      previous right pneumonectomy who suffered intractable pain from an irresectable
      left adrenal metastasis associated with metastatic retroperitoneal lymph nodes.
      Immediate pain relief was obtained, but abdominal pain of middle intensity
      recurred 6 weeks later. Although infrequently required, this procedure might be
      of value in some patients with refractory pain.

PMID- 11996274
TI  - Flow cytometric analysis of a localized malignant mesothelioma.
AB  - Malignant mesothelioma usually presents as a diffuse neoplasm. We report a
      localized malignant mesothelioma in the parietal pleura of a patient who was not
      exposed to asbestos. A complete clinical, pathologic, and immunohistochemical
      description is provided. Flow cytometric analysis showed an aneuploid DNA content
      in neoplastic cells. The patient is alive and well 8 months after complete
      surgical resection. Localized malignant mesothelioma must be included in the
      differential diagnosis in chest wall-based neoplasms.

PMID- 11996275
TI  - Spontaneous esophageal perforation presenting as meningitis.
AB  - This report describes a unique case of spontaneous esophageal perforation
      (Boerhaave's syndrome) presenting as meningitis. After a delay in diagnosis (16
      days), the patient was successfully treated with debridement, primary closure,
      and drainage. Although rare, central nervous system infections have been reported
      in association with esophageal perforation caused by instrumentation, trauma, and
      malignancy. We report this case of spontaneous esophageal perforation giving rise
      to meningitis.

PMID- 11996276
TI  - Proliferative myositis: a rare pseudosarcoma of the chest wall.
AB  - Proliferative myositis is a rare, inflammatory tumor that is often misdiagnosed
      as sarcoma. The clinical course of proliferative myositis is benign, and local
      recurrence after simple excision is uncommon. Typically, the lesion presents in
      the extremities or the head and neck. We present an unusual case of proliferative
      myositis with involvement of the anterior chest wall.

PMID- 11996277
TI  - Histological confirmation of healing of gastrobronchial fistula using a muscle
      flap.
AB  - We report a case of gastrobronchial fistula that developed after esophagectomy
      for esophageal cancer. The fistula was repaired successfully by transposing a
      pectoralis major muscle flap. Complete healing was confirmed histologically by
      epithelialization of the fistula site and at autopsy 12 months after surgery.
      Muscle flap transposition effectively repairs gastrobronchial fistula.

PMID- 11996278
TI  - Successful treatment of pulmonary hypertension with inhaled nitric oxide after
      pulmonary embolectomy.
AB  - Inhaled nitric oxide is an agent known to reduce pulmonary vascular resistance
      and prevent right heart failure. Pulmonary embolism is frequently followed by
      right heart failure and cardiogenic shock. Although successful treatment of
      patients with right ventricular failure caused by pulmonary embolism has been
      reported, clinical use of inhaled nitric oxide as an adjunct to surgical
      treatment is not in widespread use. We present a case of a 69-year-old woman with
      massive pulmonary embolism followed by right ventricular failure. After emergency
      operation, weaning from ventilation was prolonged. Pulmonary hypertension was
      decreased with low-dose inhaled nitric oxide, although pulmonary gas exchange did
      not improve. The patient was weaned successfully from ventilation 52 hours after
      operation and recovered completely. In a follow-up examination after 9 months,
      the patient is in healthy constitution with good cardiopulmonary function.

PMID- 11996279
TI  - Mitral annular aneurysm resulting from subaortic muscle resection.
AB  - We present a case of mitral annular aneurysm as a very rare complication
      developing soon after the surgical relief of subaortic stenosis. The cause of the
      aneurysm was considered to be the disruption of aorto-mitral intervalvular
      fibrosa at the initial operation. The surgical repair was successfully performed
      without compromising either aortic or mitral valvular functions. The preoperative
      transesophageal echocardiography was useful in delineating the precise anatomic
      features of this rare complication.

PMID- 11996280
TI  - Left ventricular pseudoaneurysm late after mitral valve replacement.
AB  - We report an unusual case of left ventricular pseudoaneurysm late after mitral
      valve replacement. A 60-year-old woman, who had undergone aortic and mitral valve
      replacement using mechanical prostheses 4 months previously, presented with
      severe congestive heart failure. The computed tomographic scan of the chest
      demonstrated a large mass displacing the heart anteriorly. The orifice of the
      pseudoaneurysm was successfully closed on the beating heart using partial
      femorofemoral bypass through a left thoracotomy.

PMID- 11996281
TI  - Pulmonary valve lipoma presenting as syncope.
AB  - We report a case of a pulmonary valve lipoma presenting as syncope in a 28-year
      old woman. Surgical excision of the mass was performed in urgency and the patient
      was discharged uneventfully.

PMID- 11996282
TI  - Eosinophilic heart disease with vasculitis: supported by HeartMate left
      ventricular assist device and heart transplantation.
AB  - Eosinophilic heart disease is rarely seen in clinical practice. We report a
      patient with eosinophilic heart disease who presented with acute myocardial
      infarction and congestive heart failure. Because of lack of a donor organ and
      progressive deterioration of his general condition in spite of intraaortic
      balloon pumping, a left ventricular assist device (HeartMate 1000 IP; Thermo
      Cardiosystems Inc, Woburn, MA) was implanted before development of irreversible
      multiple organ failure and was followed by heart transplantation.

PMID- 11996283
TI  - Cardiac involvement in a case of acute lymphoblastic leukemia.
AB  - We present an extremely rare case of an immunocompromised patient with a T-cell
      acute lymphocytic leukemia relapse presenting as a right atrial tumor. Problems
      in diagnosis, vulnerability due to previous immunosuppression and bone marrow
      transplant, and successful surgical excision are highlighted. Cardiac involvement
      with hematologic neoplasms should be taken with more than academic interest, as
      it may be amenable to treatment.

PMID- 11996284
TI  - Myocardial revascularization with the posterior tibial artery.
AB  - A large number of coronary artery bypass grafts are performed in Thailand. Some
      patients develop restenosed coronary arteries or stenosed graft conduits. Great
      saphenous veins, internal thoracic arteries, radial arteries, and right
      gastroepiploic arteries are used for redo coronary artery bypass grafting. But
      even with many conduits to choose from, sometimes graft conduits are not
      available. We report a case of redo coronary artery bypass grafting where the
      posterior tibial artery was harvested for the graft conduit. Clinical outcome and
      angiographic results are reported at 1 year postoperation.

PMID- 11996285
TI  - Delayed cardiac tamponade after coronary artery laceration.
AB  - Delayed cardiac tamponade after laceration of a coronary artery is unusual and
      uncommonly reported in the literature. We describe a patient in whom this
      potentially fatal complication developed 8 days after a stab wound to his chest.
      In our review of the English language literature we identified only one other
      report of delayed tamponade after coronary artery laceration.

PMID- 11996286
TI  - Upper extremity deep vein thrombosis after radial artery harvesting.
AB  - A 47-year-old diabetic man with unstable angina underwent coronary bypass surgery
      using bilateral radial arteries and left internal thoracic artery. After surgery,
      the patient suffered from severe right arm pain and swelling without any
      bleeding. The postoperative immediate digital subtraction angiogram detected
      thrombotic occlusion of the right axillary vein. We report here a rare case of
      deep vein thombosis related to radial artery harvesting.

PMID- 11996287
TI  - Single-stage anatomical repair of complete atrioventricular canal, double-outlet
      right ventricle, and cor triatriatum using ventricular septal defect
      translocation.
AB  - A 17-month-old girl underwent successful single-stage anatomic repair using a
      technique of ventricular septal defect translocation for complete
      atrioventricular canal, double-outlet right ventricle, pulmonary stenosis, cor
      triatriatum, and left superior vena cava to an unroofed coronary sinus. We
      describe the repair and present clinical and angiographic data from 9 years
      follow-up.

PMID- 11996288
TI  - Management of neonatal bronchovenous fistula after cardiopulmonary bypass.
AB  - Bronchovenous fistula is occasionally encountered after traumatic lung injury or,
      in neonates, due to ventilation injuries with high ventilatory pressures. We
      report a case of massive air embolism associated with a bronchopulmonary venous
      communication in an infant post-repair of truncus arteriosus. Selective
      ventilation of the opposite lung for 3 days sealed the fistula.

PMID- 11996289
TI  - Pulmonary atresia with intact ventricular septum and systemic-pulmonary
      collateral arteries.
AB  - Pulmonary atresia with intact ventricular septum and major systemic-pulmonary
      collateral arteries is a very rare congenital heart lesion with dismal natural
      history. Herein we report on a case of pulmonary atresia with intact ventricular
      septum with hypoplastic right ventricle, very small confluent pulmonary arteries,
      absent arterial duct, and pulmonary blood flow exclusively provided by bronchial
      type systemic-pulmonary collateral arteries that was successfully treated at our
      institution.

PMID- 11996290
TI  - Spontaneous coronary artery dissection presenting as cardiac tamponade.
AB  - Spontaneous dissection of the left main coronary artery is the least common of
      all dissections involving the coronary arteries. It usually occurs in young
      women, especially in the peripartum or early postpartum period. We describe the
      case of a 59-year-old man with no previous history of atherosclerotic heart
      disease who presented in cardiac tamponade and was found to have a spontaneous
      left main stem coronary artery dissection at cardiac catheterization. Emergency
      revascularization was carried out with the patient remaining symptom-free 4
      months after surgery.

PMID- 11996291
TI  - Images in cardiothoracic surgery. Pleuroperitoneal fistula.

PMID- 11996292
TI  - Images in cardiothoracic surgery. Radiographic demonstration of giant cardiac
      false aneurysm.

PMID- 11996293
TI  - Thoracoscopic esophagectomy combined with mediastinoscopy via the neck.
AB  - Although thoracoscopic techniques have been introduced to esophageal surgery, the
      identification of the left recurrent laryngeal nerve and lymph node dissection
      along the nerve remain quite difficult. A mediastinoscopic technique via the neck
      enables an excellent visual field to be created in the upper mediastinum,
      especially near the left recurrent laryngeal nerve. Therefore, a thoracoscopic
      esophagectomy combined with this technique allows mediastinal lymph nodes along
      the left recurrent laryngeal nerve to be easily and safely dissected.

PMID- 11996294
TI  - A method of repair for asymmetric aneurysmal dilatation of the ascending aorta.
AB  - The repair technique for an ascending aortic aneurysm depends on the portion of
      the aorta involved. An aneurysm in which the geometry of the sinotubular junction
      and the distal ascending aorta is preserved has classically been treated with
      resection and replacement with tube graft. We report an alternate method of
      resection of asymmetric aneurysmal dilatation of the ascending aorta with primary
      end-to-end anastomosis and our results of this approach with 14 patients. This
      method allows for complete resection of the aneurysm and tension-free
      anastomosis; it requires only one suture line and theoretically reduces the risk
      of bleeding. The endothelial surface of the aorta is preserved without an
      interposed synthetic graft. This method can be performed safely and the repair is
      durable at intermediate-term follow-up.

PMID- 11996295
TI  - Periareolar mediastinoscopy: a new technique.
AB  - Biopsy of anterior mediastinal or aortopulmonary nodes is usually accomplished
      through a left anterior mediastinostomy. Cosmetic concerns expressed by patients
      about scars in the neck or the upper chest led us to consider a new periareolar
      approach for mediastinoscopy. This technique has been used successfully in 10
      patients.

PMID- 11996296
TI  - Implant technique for the Jarvik 2000 Heart.
AB  - The Jarvik 2000 Heart is a silent compact axial flow impeller pump which is now
      undergoing clinical trials for both bridge to transplantation and permanent
      mechanical circulatory support. The pump is implanted into the apex of the
      failing left ventricle by left thoracotomy. A vascular graft offloads to the
      descending thoracic aorta so that only the left pleural cavity is opened. Power
      supply is through an abdominal drive line or postauricular titanium pedestal
      according to the treatment strategy.

PMID- 11996297
TI  - Remodeling of arterial conduits in coronary grafting.
AB  - In the initial decade of coronary surgery, serial angiography of internal
      thoracic artery grafts revealed increased caliber in some, decreased caliber in
      others, and "string sign" in a few, which was occasionally documented to be
      reversible. Although we speculated on possible causes of these changes, it was
      not until discovery of the endothelial role in modulating arterial diameter to
      maintain shear stress in a narrow range that we began to gain insight into the
      mechanisms responsible for remodeling of the arterial wall. This review provides
      a glimpse of the physiology and biology of arterial remodeling and summarizes
      observations on the various arterial conduits when subjected to flow alterations.

PMID- 11996299
TI  - Transmyocardial laser revascularization.

PMID- 11996298
TI  - Cause of degenerative disease of the trileaflet aortic valve: review of subject
      and presentation of a new theory.
AB  - Risk factors for both atherosclerotic aortic wall disease and degenerative
      disease of the trileaflet aortic valve are very similar if not identical. This
      correlation grows even stronger as the person advances in years. Because of this,
      it is the prevailing view that sclerosis of the trileaflet aortic valve, unless
      previously affected by septic or rheumatic endocarditis, is a disease similar in
      origin to sclerosis of the aortic wall, ie, degenerative aortic valve disease is
      arteriosclerosis of the aortic valve. Our studies challenge these views. The
      aortic valve is a functional assembly composed of the three cusps, corresponding
      sinuses, and the sino-tubular junction, characterized not only by morphologic
      features but also by its functional properties, which together create an
      environment that is optimal for distribution of diastolic pressure load and
      assures proper and timely valve opening and closure. Our more recent experiments
      also demonstrate that loss of aortic wall compliance at the level of the sinuses
      leads to significant stress-overload on the aortic leaflets and it is likely to
      start a chain of events, which begins with minor changes in their microstructure,
      then continues in more evident sclerosis, and finally ends in gross distortion or
      calcification of the cusps. The loss of the "pull-and-release" process may also
      play a part in disintegration of bioprosthetic valves and in degeneration of
      native aortic valves encased in noncompliant prostheses.

PMID- 11996300
TI  - Open lung biopsy in patients with congenital heart disease.

PMID- 11996301
TI  - Tension pneumocephalus secondary to iatrogenic subarachnoid pleural fistula:
      certain clarifications.

PMID- 11996302
TI  - Harvesting of the radial artery: skeletonization versus pedicled technique.

PMID- 11996303
TI  - Is retrograde perfusion necessary for spinal cord protection?

PMID- 11996304
TI  - Estrogen and the cholinergic system modulate visuospatial attention in monkeys
      (Macaca fascicularis).
AB  - This study determined the effects of estrogen on attention and motor speed in
      young monkeys (Macaca fascicularis). Performance on visuospatial attention and
      reaction time motor tasks was measured before ovariectomy, for 2 months after
      ovariectomy, and at 14 months after treatment with placebo or estrogen
      replacement therapy (ERT). Release time on invalid trials in the attention task
      was increased after ovariectomy and was reduced in monkeys treated with ERT. but
      not placebo. Simple reaction time was not altered after ovariectomy or treatment.
      The effects of scopolamine on attention, but not memory, in a delayed response
      task were dependent on estrogen. These observations indicate that loss of
      estrogen modulates visuospatial attention in primates and that 1 mechanism of
      this modulation is through the cholinergic system.

PMID- 11996305
TI  - Estradiol induces hypothalamic progesterone receptors but does not activate
      mating behavior in male hamsters (Mesocricetus auratus) before puberty.
AB  - This study investigated pubertal changes in neural and behavioral responses to
      estradiol. Gonadectomized pre- and postpubertal male hamsters (Mesocricetus
      auratus) were treated with 0.00, 0.05, 0.10, or 0.25 mg estradiol and tested 1
      week later for sexual behavior with a receptive female. Estradiol activated
      behavior in postpubertal, but not prepubertal, males. In contrast, estrogen
      receptor alpha (ERalpha) and progesterone receptor (PR) immunoreactivity in
      forebrain nuclei that mediate mating behavior was similar in pre- and
      postpubertal males. Thus, absence of a behavioral response before puberty is not
      associated with reduced levels of steroid receptors. Because estradiol induced PR
      in prepubertal males, these data also suggest that ERa is functional before
      puberty. Therefore, gonadal steroids facilitate male reproductive behavior only
      after as-yet-unidentified developmental processes occur during puberty.

PMID- 11996306
TI  - The effect of labor on olfactory exposure learning within the first postnatal
      hour.
AB  - Thirty-one neonates delivered by cesarean section were exposed to an odor for 30
      min shortly after birth. Fifteen births had uterine labor contractions before
      delivery; 16 were without contractions. All babies were later tested (median age
      = 80 hr) for their responses to the familiar exposure odor and a novel odor
      presented on either side of the face. Overall, the babies spent more time turned
      toward the exposure odor than toward the novel scent. Babies in the labor
      condition, but not those bom without labor, displayed a significant preference
      for the exposure odor. Norepinephrine (NE) levels were higher in babies who
      oriented preferentially toward the exposure odor. Brief exposure immediately
      after birth is sufficient for the development of olfactory learning. Heightened
      learning by neonates from births with contractions may reflect locus coeruleus
      and NE activation. Olfactory learning may therefore be particularly efficient
      shortly after birth.

PMID- 11996307
TI  - How synchronization properties among second-order sensory neurons can mediate
      stimulus salience.
AB  - Spatial patterns of glomerular activity in the vertebrate olfactory bulb and
      arthropod antennal lobe reflect an important component of first-order olfactory
      representation and contribute to odorant identification. Higher concentration
      odor stimuli evoke broader glomerular activation patterns, resulting in greater
      spatial overlap among different odor representations. However, behavioral studies
      demonstrate results contrary to what these data might suggest: Honeybees are
      more, not less, able to discriminate among odorants applied at higher
      concentrations. Using a computational model of the honeybee antennal lobe, the
      authors show that changes in synchronization patterns among antennal lobe
      projection neurons, as observed electrophysiologically, could parsimoniously
      underlie these observations. The results suggest that stimulus salience, as
      defined behaviorally, is directly correlated with the degree of synchronization
      among second-order olfactory neurons.

PMID- 11996308
TI  - Behavioral models of odor similarity.
AB  - Carbon chain length in several classes of straight-chain aliphatic odorants has
      been proposed as a model axis of similarity for olfactory research, on the basis
      of successes of studies in insect and vertebrate species. To assess the influence
      of task on measured perceptual similarities among odorants and to demonstrate
      that the systematic similarities observed within homologous odorant series are
      not task specific, the authors compare 3 different behavioral paradigms for rats
      (olfactory habituation, generalization, and discrimination). Although overall
      patterns of odorant similarity are consistent across all 3 of these paradigms,
      both quantitative measurements of perceptual similarity and comparability with 2
      deoxyglucose imaging data from the olfactory bulb are dependent on the specific
      behavioral tasks used. Thus, behavioral indices of perceptual similarity are
      affected by task parameters such as learning and reward associations.

PMID- 11996309
TI  - Neurotoxic lesions of the rat perirhinal cortex fail to disrupt the acquisition
      or performance of tests of allocentric spatial memory.
AB  - Rats with neurotoxic lesions of the perirhinal cortex (n = 9) were compared with
      sham controls (n = 14) on a working memory task in the radial arm maze. Rats were
      trained under varying levels of proactive interference and with different
      retention intervals. Finally, performance was assessed when the maze was switched
      to a novel room. None of these manipulations differentially impaired rats with
      perirhinal lesions. Rats were next trained on delayed matching-to-place in the
      water maze. Even with retention delays of 30 min, there was no evidence of a
      deficit. Although interactions between the perirhinal cortex and hippocampus may
      be important for integrating object-place information, the perirhinal cortex is
      often not necessary for tasks that selectively tax allocentric spatial memory.

PMID- 11996310
TI  - Impairments in negative patterning, but not simple discrimination learning, in
      rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis.
AB  - Rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis (NBM)
      and sham-operated rats were trained in either a simple discrimination paradigm
      assessing simple association learning or a negative patterning paradigm assessing
      configural association learning. In the simple discrimination task, rats were
      reinforced for responding to a light but were not reinforced for responding to a
      tone. In the negative patterning discrimination task, rats were reinforced for
      responding to either a light or a tone presented alone but were not reinforced
      for responding to both stimuli presented simultaneously. Simple discrimination
      learning was not affected, whereas acquisition of negative patterning was
      impaired by NBM lesions. Impaired configural association learning may reflect a
      loss in the ability of rats with NBM lesions to attend to multiple sensory
      stimuli or to cope with conflicting response strategies.

PMID- 11996311
TI  - Area postrema lesions impair flavor-toxin aversion learning but not flavor
      nutrient preference learning.
AB  - Rats with lesions of the area postrema (APX) or sham lesions were trained to
      associate flavored solutions with positive or negative postingestive
      consequences. The APX rats were similar to controls in learning preferences for
      flavors paired with concurrent intragastric infusions of maltodextrin or corn oil
      and for a flavor paired with delayed maltodextrin infusions. In contrast, the APX
      rats displayed impaired aversion learning for flavors paired with toxic drug
      treatments (lithium chloride infusion or methylscopolamine injection). The
      aversion learning deficit ranged from mild to total, depending on training
      procedures. These findings confirm the important role of the area postrema in
      flavor-toxin learning but provide no evidence for its involvement in flavor
      nutrient conditioning.

PMID- 11996312
TI  - Disconnection of the basolateral amygdala complex and nucleus accumbens impairs
      appetitive pavlovian second-order conditioned responses.
AB  - There is considerable evidence that the basolateral complex of the amygdala (ABL)
      is involved in learning about the motivational value of otherwise neutral
      stimuli. The authors examined the role in this function of the ABL and one of its
      major efferent structures. the nucleus accumbens. Male Long-Evans rats received
      either sham, ipsilaterally, or contralaterally placed unilateral lesions of the
      ABL and accumbens and were trained in an appetitive Pavlovian second-order
      conditioning task. Sham-lesioned and ipsilaterally lesioned rats acquired the
      task normally, but contralaterally lesioned rats, in which the ABL and accumbens
      were functionally disconnected, failed to acquire second-order conditioned
      responses (although they did acquire second-order conditioned orienting
      responses). The results suggest that the ABL and accumbens are part of a system
      critical for processing information about learned motivational value.

PMID- 11996313
TI  - The role of the hippocampus in memory for the temporal order of a sequence of
      odors.
AB  - Memory for the temporal order of a sequence of odors was assessed in rats. A
      sequence of 5 odors mixed in sand was presented in digging cups, 1 at a time, to
      each rat in a sequence that varied on each trial. A reward was buried in each
      cup. After the 5th odor, 2 of the previous 5 odors were presented simultaneously;
      to receive a reward, the rat had to choose the odor that occurred earliest in the
      sequence. Temporal separations of 1, 2, or 3 represented the number of odors that
      occurred between the 2 odors in the sequence. Once a preoperative criterion was
      reached, each rat received a hippocampal (HIP) or cortical control lesion and was
      retested on the task. On postoperative trials, the HIP group was impaired
      relative to controls. However, the HIP group could discriminate between the
      odors. The data suggest that the hippocampus is involved in separating sensory
      events in time so that I event can be remembered separately from another event.

PMID- 11996314
TI  - Differential effects of methamphetamine and haloperidol on the control of an
      internal clock.
AB  - Humans and animals process temporal information as if they were using an internal
      stopwatch that can be stopped and reset, and whose speed is adjustable. Previous
      data suggest that dopaminergic drugs affect the speed of this internal stopwatch.
      Using a paradigm in which rats have to filter out the gaps that (sometimes)
      interrupted timing, the authors found that methamphetamine and haloperidol also
      affect the stop and reset mechanism of the internal clock, possibly by modulating
      attentional components that are dependent on the content and salience of the
      timed events. This is the first report of both clock and attentional effects of
      dopaminergic drugs on interval timing in the same experimental setting.

PMID- 11996315
TI  - 3,4 methylenedioxymethamphetamine (ecstasy) impairs eight-arm radial maze
      performance and arm entry pattern in rats.
AB  - The recreational use of 3,4 methylenedioxymethamphetamine (ecstasy) in humans has
      been associated with memory impairment. The present study examined whether
      ecstasy impairs short- and long-term working memory and the pattern of arm
      entries in rats tested in the 8-arm radial maze with a 2-hr delay. After
      completing the training session, the rats were given a single dose of ecstasy (1,
      2, or 3 mg/kg ip) 20 min before the test. The highest dose slightly affected
      short-term working memory. Under conditions of delay, there was a progressive
      deficit in long-term working memory, starting from 1 mg/kg. Under both test
      conditions, 2 and 3 mg/kg flattened the pattern of arm entry. None of the doses
      caused hyperlocomotion or stereotypy in the radial maze. These findings suggest
      that acute ecstasy mainly affects the long-term components of working memory and
      disrupts the pattern of arm entry in a way similar to serotonergic agents.

PMID- 11996316
TI  - Physiological and behavioral effects of acute ethanol hangover in juvenile,
      adolescent, and adult rats.
AB  - This study examined differential responding of juvenile, adolescent, and adult
      rats after intoxication from an acute alcohol challenge. Experiment I generated
      blood ethanol curves for subjects 25, 35, or 110 days postnatal, after doses of
      2.0 or 4.0 g/kg, assessing elimination rates and time of drug clearance.
      Experiment 2 compared ethanol's initial hypothermic and delayed hyperthermic
      effect across age by 48-hr temperature measurement with telemetry. At clearance
      or 24 hr after alcohol exposure, Experiment 3 tested subjects for changes in
      acoustic startle reactivity and ultrasonic vocalization (USV). Younger rats
      showed an absent or reduced tendency for residual hyperthermia, and adults showed
      alterations in USV observed as aftereffects of intoxication, despite greater
      initial blood alcohol levels and ethanol hypothermia in the former. The lesser
      ethanol hangover effects in weanlings and adolescents may be due in part to
      faster ethanol elimination at these ages compared with adults.

PMID- 11996317
TI  - Cocaine-induced suppression of saccharin intake: a model of drug-induced
      devaluation of natural rewards.
AB  - In Experiment 1, water-deprived Sprague-Dawley rats were given 5 min access to
      saccharin. This tube retracted, an empty tube advanced, and the rats were given 1
      hr to lick the empty tube on a fixed-ratio 10 lick contingency to self-administer
      saline or cocaine (0.33 mg/infusion) via an intravenous catheter. The results
      showed that rats avoided intake of saccharin after saccharin-cocaine pairings and
      that greater avoidance of the gustatory cue was associated with greater cocaine
      self-administration. In Experiment 2, a similar dose-response function was
      obtained with either the empty tube or a lever as the operant. In Experiment 3,
      avoidance of the saccharin cue and the propensity to self-administer cocaine were
      maintained after at least 1 month of abstinence. As such, this paradigm may be
      useful as a model of cue-induced craving and drug-induced devaluation of natural
      rewards.

PMID- 11996318
TI  - Caffeine-reinforced conditioned flavor preferences in rats.
AB  - In 4 experiments, rats were trained to associate 1 of 2 differently flavored
      solutions with caffeine. During later 2-bottle extinction tests, they
      consistently preferred flavors that had been previously mixed with 2 lower (0.25
      and 0.125 mg/ml), but not 2 higher (0.5 and 0.75 mg/ml), caffeine concentrations.
      Hunger during conditioning increased the size of these preferences, but neither
      preexposure to unflavored caffeine nor hunger during the choice test had any
      effect on them. Because caffeine is noncaloric, this last finding strengthens the
      hypothesis that hunger enhances the expression of only calorie-based conditioned
      flavor preferences. More fundamentally, the present results represent the first
      clear evidence that, through Pavlovian conditioning, rats can develop preferences
      for flavors associated with caffeine.

PMID- 11996319
TI  - Conditioning of a flavor aversion in rats by amygdala kindling.
AB  - Rats received 30 stimulations and 30 sham stimulations (the lead was attached to
      the subjects but no current was delivered) to the left basolateral amygdala in a
      quasirandom sequence. Stimulations were preceded by the presentation of 1
      flavored solution conditional stimulus (CS+); sham stimulations were preceded by
      the presentation of another flavored solution, CS-. As kindled motor seizures
      developed, the rats began to consume significantly less of the CS+ than the CS-.
      Moreover, at the end of the experiment, the rats consumed significantly less of
      the CS+ than the CS- during a 20-min conditioned flavor preference test in which
      both solutions were available simultaneously. These findings confirm and extend
      the recent report that interictal changes in defensive behavior can be
      conditioned by amygdalar kindling.

PMID- 11996320
TI  - Long-term study of chronic oral aluminum exposure and spatial working memory in
      rats.
AB  - The authors report an effort to advance animal models that mimic the cognitive
      decline of Alzheimer's disease. Rats were trained and repeatedly tested in a
      spatial delayed matching-to-position paradigm in the water maze, with the
      location of the submerged platform changing between, but not within, days. After
      Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was
      tested in Trial 2. Young rats quickly acquired this task and were repeatedly
      tested after different intervals over 7 months, with a slight increase in
      performance toward the end of testing, but no difference in latencies between
      delays. Oral long-term treatment of 1 group with 0.1% aluminum caused no delay
      dependent working memory deficit. This testing protocol may enable between- and
      within-subject long-term assessment of spatial working memory before and after
      drug treatment and may prove useful in animal models of progressive cognitive
      decline.

PMID- 11996321
TI  - The in vivo metabolism of tibolone in animal species.
AB  - The in vivo tissue distribution and metabolism of tibolone was studied in
      different animals to further investigate the compound's tissue-specificity.
      Tibolone's metabolism was studied in vivo in rats and rabbits by administration
      of [16-3H]-tibolone and the metabolic pattern was determined in urine and faeces
      after oral administration to female rats and dogs. The main excretory pathway was
      found to be excretion in the faeces. Important phase-I metabolic routes were the
      reduction of the 3-keto to the 3a- or 3beta-hydroxy functions with a preference
      for 3alpha-OH in rats and for 3beta-OH in dogs. To a lesser extent, hydroxylation
      reactions at C2 and C7, and a shift of the delta5(10)-double bond to a delta4(5)
      position also occurred. The main phase-II metabolic route was sulphate
      conjugation of the hydroxyl groups at C3 and C17. Since the oxidation reactions
      form only a minor part of the metabolism of tibolone, it is concluded that the
      cytochrome P450 enzymes do not play an important role in tibolone's metabolism.
      For both phases, quantitative differences were found between the species. In
      human similar metabolites are found. Profiling of the target organs in female
      rats and rabbits showed a tissue-specific distribution of metabolites. The
      majority of the metabolites existed as sulphate conjugates and no glucuronidated
      conjugates were observed. The same metabolites were found in both the circulation
      and the tissues. However, different tissues had quantitatively different
      metabolic profiles.

PMID- 11996322
TI  - Biometrical evaluation of bioequivalence trials using a bootstrap individual
      direct curve comparison method.
AB  - Bioequivalence of two medicinal, or veterinary, products is established by
      comparing the mean of bioavailability measures, such as AUC and Cmax, following
      administration of the test (T) and reference (R) products. However, the use of
      these parameters has several drawbacks, e.g. they do not take into consideration
      the overall pharmacokinetic profile shape. Therefore, concerns have been raised
      regarding their appropriateness for assessment of bioequivalence. To overcome the
      limitations of these bioequivalence parameters, direct curve comparison metrics
      methods were recently proposed on an average basis. In this paper, an individual
      based direct curve comparison method for assessing bioequivalence is proposed.
      The bioequivalence of T and R in each subject is evaluated by a new curve
      comparison metrics delta. The metrics delta is the absolute sum of the difference
      between two curves. The significance of the metrics for each subject is assessed
      by bootstrapping. An overall bioequivalence of T and R may be considered if less
      than 25% of the subjects show statistically different profiles.

PMID- 11996323
TI  - Absorption, distribution and excretion of 3H-labeled cephaeline- and emetine
      spiked ipecac syrup in rats.
AB  - The maximum plasma radioactivity levels of tritium (3H)-labeled cephaeline,
      (24.3, 28.7 and 40.6 ng eq./mL) were reached at 2.00-3.33 hours following oral
      dosing of ipecac syrup. The maximum plasma radioactivity levels of 3H-emetine
      (2.71, 6.47 and 9.62 ng eq./mL) were reached at 1.08-2.33 hours following ipecac
      syrup administration. The Cmax values of 3H-cephaeline were followed by a
      biexponential decrease with half-lives t 1/2(lambda z) of 3.45-9.40 hours. On the
      other hand, the t 1/2 (lambda z)of 3H-emetine were 65.4-163 hours, which revealed
      a biexponential decrease. The radioactivity of both tritium-labeled compounds was
      distrbuted maximally in most tissues at 24 hours. For 3H-cephaeline, the maximum
      radioactivity levels in tissues were approximately 100-150 times greater than in
      plasma. For 3H-emetine, the radioactivity levels in tissues were approximately
      1000-3000 times greater than in plasma. Tissue radioactivity levels decreased at
      a substantially slower rate than that observed in plasma. Tissue radioactivity of
      3H-emetine decreased more slowly than that of 3H-cephaeline. For 3H-cephaeline,
      the cumulative biliary excretion of radioactivity was 57.5% at 48 hours. The
      cumulative urinary and fecal excretion of radioactivity in these rats was 16.5%
      and 29.1%, respectively, of the dose at 48 hours following dosing. For 3H
      emetine, the cumulative biliary excretion of radioactivity was 12.5% at 48 hours.
      The cumulative urinary and fecal excretion of radioactivity was 9.4% and 34.1%,
      respectively, of the administered dose at 48 hours. The radioactivity level of 3H
      emetine remaining in the carcasses at 48 hours was equivalent to approximately
      50% of the dose. A portion of each tritium-labeled compound was subjected to
      entero-hepatic circulation. Thus, the absorption rate of 3H-cephaeline and 3H
      emetine was estimated to be approximately 70% on the basis of the data obtained
      from excretion studies. There was no difference in the absorption process between
      these two compounds. However, the difference was admitted in the biliary
      clearance, which is the main excretion route of both compounds. Delayed excretion
      of 3H-emetine may be primarily due to its resorption as related to entero-hepatic
      circulation and tissue retention. This study has determined the absorption,
      distribution and excretion of 3H-cephaeline and 3H-emetine in rats.

PMID- 11996324
TI  - Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac
      syrup in rats.
AB  - The metabolism of cephaeline and emetine, which are the primary active components
      of ipecac syrup, were investigated in rats. Cephaeline-6'-O-glucuronide was found
      to be a biliary metabolite of cephaeline. Cephaeline (6'-O-demethylemetine) and 9
      O-demethylemetine were observed to be enzyme-hydrolyzed biliary metabolites of
      emetine. Cephaeline was conjugated to glucuronide, while emetine was demethylated
      to cephaeline and 9-0-demethylemetine, and may be conjugated to glucuronides
      afterwards. Urine, feces and bile were collected from rats within 48 hours
      following the administration of ipecac syrup containing tritium (3H)--labeled
      cephaeline or emetine. Metabolites were separated and quantified by thin layer
      chromatography (TLC) or high-performance liquid chromatography (HPLC). Biliary
      and urinary excretion rates of 3H-cephaeline were 57.5% and 16.5% of the dose,
      respectively. Cephaeline-6'-O-glucuronide was comprised 79.5% of biliary
      radioactivity and 84.3% of urinary radioactivity. Unchanged cephaeline was
      detected in 42.4% of the dose in feces. Biliary excretion rate of 3H-emetine was
      6.9% of the dose. Emetine, cephaeline and 9-0-demethylemetine comprised 5.8%,
      43.2% and 13.6% in hydrolyzed bile, respectively. There were no emetine-derived
      metabolites in urine or feces. The occurrence of unchanged emetine was 6.8% and
      19.7% of the dose in urine and feces, respectively.

PMID- 11996325
TI  - Distribution and elimination characteristics of 111In-DTPA-D-phe1-octreotide and
      111In-DTPA-L-phe1-octreotide in rats.
AB  - The present study compares distribution and elimination characteristics of 111In
      DTPA-D-Phe1-octreotide and 111In-DTPA-L-Phe1-octreotide in rats and evaluated the
      effect of the replacement of the terminal L-phenylalanine by D-phenylalanine on
      pharmacokinetic profiles of the radiolabelled peptides. Both agents exhibited
      rapid radioactivity clearance from the blood and most organs and tissues with no
      systematic and significant differences in activity accumulation. The long-term
      retention and high radioactivity concentrations for both compounds under study
      were found in the kidneys and organs with a high density of somatostatin
      receptors, such as the pancreas and adrenals. The residence times in these organs
      were longer for 111In-DTPA-D-Phe1-octreotide in comparison with 111In-DTPA-L-Phe1
      octreotide. The major elimination pathway for both radiolabelled peptides was
      relatively rapid excretion into the urine. Analysis of the renal handling by an
      employment of the perfused rat kidney showed that both peptides were eliminated
      mainly by the mechanism of glomerular filtration. Rat liver perfusion experiments
      confirmed a very low value of bile clearance of radioactivity for both agents
      under study.

PMID- 11996326
TI  - Plasma atrial natriuretic peptide levels in essential hypertension after
      treatment with verapamil.
AB  - The aim of this study was to evaluate the long term effects of the selective Ca2+
      blocker verapamil on atrial natriuretic peptide (ANP) levels in patients with
      moderate essential hypertension. The drug was given orally in a daily dose of 300
      mg for 30 days. At the end of this clinical trial, plasma ANP levels increased by
      16.14% despite the drop in blood pressure while left atrial and ventricular
      diameters remained unchanged. These findings indicate that the increase of ANP
      plasma levels is not the result of a mechanical load on the left cardiac chambers
      but the result of a pharmacological action. These observations also indicate that
      verapamil exerts part of its antihypertensive action by increasing ANP plasma
      levels.

PMID- 11996327
TI  - Effect of food on the pharmacokinetics of fiduxosin in healthy male subjects.
AB  - The effect of food on the pharmacokinetics of fiduxosin, a novel selective
      alpha1a-receptor antagonist, was determined in healthy male subjects. This was a
      Phase I, open-label, single-center, randomized, two-period, crossover, single
      oral dose study of fiduxosin. Healthy male subjects (N= 14) were administered
      single oral doses of 30 mg of fiduxosin under fasting or nonfasting (1026 Kcal,
      54 g fat, 46% calories from fat) conditions in each period. Fiduxosin plasma
      concentration profiles were used to assess fiduxosin pharmacokinetics. The mean
      Cmax, Tmax, AUC(infinity), CL/F and Vbeta/F values under fasting and nonfasting
      conditions were 34.3 and 150 ng/mL, 5.4 and 5.4 h, 822 and 1940 ng x h/mL, 42.5
      and 17.2 L/h, and 924 and 235 L, respectively. The harmonic mean t 1/2 under
      fasting and nonfasting conditions were 13.9 and 9.28 h, respectively. Food
      significantly increased the bioavailability of fiduxosin. Under the nonfasting
      regimen, the Cmax central value was more than 4-fold and the AUC(infinity)
      central value more than 2-fold the central value of the fasting regimen. Tmax was
      not significantly different between fasting and nonfasting regimens. Food also
      decreased fiduxosin oral clearance (CL/F) by 60% and volume of distribution
      (Vbeta/F) by 75%.

PMID- 11996328
TI  - Pharmacokinetics and efficacy of 40 ml ropivacaine 7.5 mg/ml (300 mg), for
      axillary brachial plexus block--an open pilot study.
AB  - In this study, the pharmacokinetics, tolerability and efficacy of 40 ml of
      ropivacaine 7.5 mg/ml (300 mg) for axillary brachial plexus block were
      investigated. With institutional review board approval, 10 patients presenting
      for surgery of the upper limb were enrolled in this open study. The axillary
      plexus was identified with a nerve stimulator and the study drug was injected
      into the neurovascular sheath. Fifteen venous blood samples were obtained from
      each patient for pharmacokinetic measurements over a 24-h period. All blocks were
      sufficient for surgery after 45 min without any need for supplemental analgesia
      or general anesthesia. The mean (SD) peak plasma concentration was 2.3 (0.8) mg/l
      at median tmax 54 min (range 16-92 min). The mean (SD) maximum free plasma
      concentration was calculated to be 0.12 (0.06) mg/l (range 0.07-0.29 mg/l). The t
      1/2 was about 6 h. There were no clinical signs or symptoms of central nervous
      system and/or cardiac toxicity in any patient. Ropivacaine 7.5 mg/ml, used in a
      dose of 300 mg, was effective and well tolerated for axillary brachial plexus
      block.

PMID- 11996329
TI  - Evaluation of the bioequivalence of tablets and capsules containing the novel
      anticancer agent R115777 (Zarnestra) in patients with advanced solid tumors.
AB  - R115777 (Zamestra) is a novel anticancer agent, currently undergoing phase III
      clinical testing. An open, cross-over trial was performed in 24 patients with
      solid tumors to compare the bioavailability of a new tablet formulation with the
      standard capsule formulation. Both dosage forms were administered once daily in
      doses of 300 or 400 mg. Patients received R115777 as a capsule on day I and as a
      tablet on day 2, or vice versa. Blood samples were drawn up to 24 hours after
      drug intake and R115777 levels were measured using a validated high performance
      liquid chromatography (HPLC) method. The following pharmacokinetic parameters
      were determined and compared for the two formulations: time to maximal plasma
      concentration (Tmax), half-life (t 1/2), maximal plasma concentration (Cmax) and
      area under the curve at twenty-four hours (AUC24h). For the latter two
      parameters, 90% classical confidence intervals of the ratio tablet/capsule were
      calculated after a log-transformation, using an Analysis of Variance (ANOVA). For
      t 1/2 and Tmax, no statistically significant differences were found between
      tablet and capsule. The point estimates of the ratio's of the log-normalized Cmax
      and AUC24h were 0.94 and 0.92, respectively, and the 90% confidence intervals
      were 0.81-1.09 and 0.83-1.03, which is within the critical range for
      bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic
      parameters demonstrate that the capsule and tablet formulations of R115777 are
      interchangeable.

PMID- 11996330
TI  - Progress in the development and use of ferrate(VI) salt as an oxidant and
      coagulant for water and wastewater treatment.
AB  - This paper reviews the progress in preparing and using ferrate(VI) salt as an
      oxidant and coagulant for water and wastewater treatment. The literature revealed
      that due to its unique properties (viz. strong oxidizing potential and
      simultaneous generation of ferric coagulating species), ferrate(VI) salt can
      disinfect microorganisms, partially degrade and/or oxidise the organic and
      inorganic impurities, and remove suspended/colloidal particulate materials in a
      single dosing and mixing unit process. However, these findings have not yet lead
      to the full-scale application of ferrate(VI) in the water industry owing to
      difficulties associated with the relatively low yield of ferrate(VI), the
      instability of the chemical depending on its method of preparation, and the lack
      of adequate studies that have demonstrated its capabilities and advantages over
      existing water and wastewater treatment methods. Fundamental study is thus
      required to explore the new preparation methods focusing on increasing the
      production yield and product's stability and avoiding using hypochlorite or
      chlorine as the oxidant. Also, the application of ferrate(VI) in drinking water
      treatment has not been studied systematically and future work in this field is
      recommended.

PMID- 11996331
TI  - Submerged aquatic vegetation-based treatment wetlands for removing phosphorus
      from agricultural runoff: response to hydraulic and nutrient loading.
AB  - Submerged aquatic vegetation (SAV) communities exhibit phosphorus (P) removal
      mechanisms not found in wetlands dominated by emergent macrophytes. This includes
      direct assimilation of water column P by the plants and pH-mediated P
      coprecipitation with calcium carbonate (CaCO3). Recognizing that SAV might be
      employed to increase the performance of treatment wetlands, we investigated P
      removal in mesocosms (3.7 m2) stocked with a mixture of taxa common to the
      region: Najas guadalupensis, Ceratophyllum demersum, Chara spp. and Potamogeton
      illinoensis. Three sets of triplicate mesocosms received agricultural runoff from
      June 1998 to February 2000 at nominal hydraulic retention times (HRTs) of 1.5,
      3.5 or 7.0 days. Mean total P (TP) loading rates were 19.7. 8.3 and 4.5 g/m2/yr.
      After eight months of operation. N. guadalupensis dominated the standing crop
      biomass and P storage, whereas C. demersum exhibited the highest tissue P
      content. Chara spp. was prominent only in the 7.0)-day HRT treatments while P.
      illinoensis largely disappeared. Inflow soluble reactive phosphorus (SRP) (10 163
      microg/L) was reduced consistently to near the detection limit (2 microg/L) in
      the 3.5- and 7.0-day HRT treatments, and to a mean of 9 microg/L in the 1.5-day
      HRT treatment. The mean inflow TP concentration (10(7) microg/L) was reduced to
      52, 29 and 23 microg/L in the 1.5-, 3.5- and 7.0-day HRT treatments,
      respectively. Total P concentrations in new sediment (mean= 641, 408 and 459
      mg/kg in the 1.5-. 3.5-, and 7.0-day HRT mesocosms, respectively) were much
      higher than in the muck soil used to stock the mesocosms (236 mg/ kg). The
      calcium content of new sediment was twice that of the muck soil (16.5% vs. 7.6%),
      demonstrating that CaCO3 production and, perhaps, coprecipitation of P occurred.
      We observed no nocturnal remobilization of SRP despite diel fluctuations in pH
      and dissolved oxygen. Mean outflow TP (21 microg/L) from a 147 ha SAV wetland (4
      day nominal HRT) was similar to mean outflow TP in the 3.5-day and 7.0-day HRT
      treatments. The mesocosms adequately mimicked P removal and other important
      characteristics of the larger system and can be used to address research
      questions regarding treatment performance of full-scale SAV wetlands. Available
      data suggest that the incorporation of SAV communities into the stormwater
      treatment areas may benefit Everglades restoration.

PMID- 11996332
TI  - Method for the measurement of the diffusion coefficient of benzalkonium chloride.
AB  - Biofilm formation on the optical ports of cameras and underwater sensors is the
      primary cause of their reduced useful deployment time. The use of a transparent
      hydrogel coating containing the cationic surfactant benzalkonium chloride has
      been shown to extend the deployment times for up to 12 weeks for these
      instruments. In order to predict the effective lifetime of these coatings it was
      necessary to obtain the diffusion coefficient of the benzalkonium chloride used
      in the coatings. Benzalkonium chloride can have different alkyl chain lengths
      ranging from C8H17 to C18H37 with chain length greatly affecting its chemical
      properties. The benzalkonium chloride materials investigated here were mixtures
      of C12H25 and C14H29 as well as C14H29 on its own. These materials were selected
      for their proven biofilm resistant qualities. The diaphragm diffusion cell
      technique was investigated for its applicability to the measurement of diffusion
      coefficients of molecules with surfactant properties and the ability to form
      micelles. The method was found to be satisfactory for the cationic surfactant
      benzalkonium chloride. The average value of the membrane cell integral diffusion
      coefficient D was 7.78 x 10(-6) cm2 s(-1) at 25 degrees C and there was no
      significant effect of alkyl chain length on the measured value of D.

PMID- 11996333
TI  - Occurrence of phthalates and bisphenol A and F in the environment.
AB  - Certain xenoestrogens, namely bisphenol A (BPA), bisphenol F (BPF), butylbenzyl
      phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl)phthalate (DEHP),
      were measured in various compartments (surface water, sediments, sewage treatment
      plant effluents, sewage sludge, dump water, liquid manure) in order to contribute
      to a better understanding of exposure to these compounds in different
      environments. Hundred and sixteen surface-water samples and 35 sediments from
      rivers, lakes and channels, 39 sewage effluents, and 38 sewage sludges were
      collected in Germany. Furthermore, ten liquid manure, two waste-dump and two
      compost-runoff water samples were also analysed. BPA measurements showed low
      concentrations from 0.0005 to 0.41 microg L(-1) in surface water, in sewage
      effluents from 0.018 to 0.702 microg L(-1), in sediments from 0.01 to 0.19 mgkg(
      1) and in sewage sludge from 0.004 to 1.363mgkg(-1) dw. Measured concentrations
      of BPF were clearly lower than BPA in all environmental media. DEHP dominated the
      phthalate concentrations, which ranged from 0.33 to 97.8 microg L(-1) (surface
      water), 1.74 to 182 microg L(-1) (sewage effluents), 27.9 to 154 mgkg(-1) dw
      (sewage sludge) and 0.21 to 8.44 mgkg(-1) (sediment). DBP was found only in minor
      concentrations and BBP, only in a few samples in low amounts. Very high
      concentrations of BPA and phthalates were confirmed in waste dump water and
      compost water samples as well as in the liquid manure samples.

PMID- 11996334
TI  - Distribution and activity of ammonia oxidizing bacteria in a large full-scale
      trickling filter.
AB  - The biofilm in a full-scale nitrifying trickling filter (NTF) treating municipal
      wastewater has been investigated with microbiological methods using fluorescence
      in situ hybridization (FISH) with 16S rRNA oligonucleotide probes in combination
      with confocal laser scanning microscopy (CLSM) and mathematical modeling using a
      dynamic multi-species biofilm reactor model. Ammonia oxidizing bacteria (AOB)
      were found to belong to the genus Nitrosomonas at different depths in the NTF at
      every sampling occasion, corresponding to different long-term operational
      conditions for the NTF. Both the measurements and the corresponding simulated
      predictions showed the same general trend of a decrease with filter depth of the
      amount of biofilm, the proportion of AOB to all bacteria and the total amount of
      AOB. The latter decreased by several times from top to bottom of the NTF.
      Measurements and simulations of potential ammonium oxidizing activity in the
      biofilm also showed a decreasing activity with depth in the NTF, which generally
      was operating at close to complete nitrification. However, no difference was
      observed when the activity was normalized to the amount of biofilm, despite
      decreasing proportions of AOB to all bacteria with depth in the NTF. This could
      be explained by diffusion limitations in the biofilm from the upper parts of the
      NTF according to the biofilm reactor model. The relatively good agreement between
      the simulations and the measurements shows that the kind of biofilm reactor model
      used can qualitatively describe an averaged behavior and averaged composition of
      the biofilm in the reactor.

PMID- 11996335
TI  - Decolorization of textile dyes by laccases from a newly isolated strain of
      Trametes modesta.
AB  - Four ligninolytic fungi, Trametes modesta, Trametes hirsuta, Trametes versicolor
      and Sclerotium rolfsii, were compared for their ability to produce laccases. The
      fungal laccases were screened for their ability to decolorize eight synthetic
      dyes (anthraquinone, azo, indigo and triarylmethane). The decolorization rate
      depended both on the source of the enzyme preparation and on the structure of the
      dye. Based on laccase production and dye decolorizing ability, T. modesta was
      selected for further studies. All the tested dyes were decolorized by the T.
      modesta laccase most efficiently under acid conditions (pH 3-6) but the optimum
      pH for decolorization of the individual dye varied. The decolorization rate of
      this laccase increased with the rise in temperature to 50-60 degrees C. The
      decolorization efficiency of T. modesta laccase was improved remarkably in the
      presence of mediators like 1-hydroxybenzotriazole and 2-methoxyphenothiazine.

PMID- 11996336
TI  - Distribution and sources of polycyclic aromatic hydrocarbons in the sediment of a
      sub-tropical coastal wetland.
AB  - Sediment cores (0-35cm below surface) from twelve sampling stations in the Mai Po
      and Inner Deep Bay Ramsar Site of Hong Kong were retrieved in the period March
      December 1999. Vertical profiles of 15 priority polycyclic aromatic hydrocarbons
      (PAHs) in each sediment core were determined. Ranges of total PAH concentration,
      [sigmaPAH], in the wetland sediment were 0.18-0.83 (N = 0.36) microg/g dried
      sediment (mudflats) and 0.63-0.96 (x = 0.77) microg/g dried sediment (mangroves).
      A decreasing trend in depth averaged [sigmaPAH] was observed from the landward
      end towards the seaward end of the Marshes. On the mudflats, vertical profiles of
      the PAHs were quite uniform. At the fringe of the Mai Po mangroves, significantly
      higher concentration of all PAHs was observed at the upper 0 to -8 cm layer. No
      significant difference in the distribution patterns of the 15 priority PAHs in
      summer and winter was observed. This indicates that distribution of PAHs in the
      sediment of the Mai Po Marshes is not very sensitive to sub-tropical climatic
      changes of the region. Two PAH isomer ratios, [Phen]/([Phen] + [Anthra]) and
      [Pyrene]/([Pyrene] + [Fluoran]), were used to identify potential sources of PAH
      contamination in the wetland. Results revealed that local deposition is a more
      important source than long-range atmospheric transportation.

PMID- 11996337
TI  - Comparison of bacterial regrowth in distribution systems using free chlorine and
      chloramine: a statistical study of causative factors.
AB  - Bacterial regrowth was investigated over a 15-month period in distribution
      systems (DSs) of Durham and Raleigh in North Carolina. These two water utilities
      were chosen because they are adjacent to one another, have similar service area
      characteristics, and treat surface waters of similar characteristics with
      conventional processes (coagulation-sedimentation and dual-media filtration). The
      finished waters have similar chemical quality and regrowth potential as measured
      by assimilable organic carbon (AOC). The major difference in treatment is the
      choice of final disinfectants (chlorine in Durham and chloramine in Raleigh). Ten
      sampling sites (monthly sampling) were chosen in each system to give wide
      geographic coverage and correspondingly, a wide range of water residence times.
      Significant losses were observed in both chlorine and chloramine residual in the
      DSs that produced bacterial regrowth as measured by heterotrophic plate count
      (HPC). The frequency distributions for log HPC (133 observations from Durham and
      135 observations from Raleigh) were statistically the same in the chlorinated and
      chloraminated DSs. A correlation analysis indicated that disinfectant residual is
      the most important factor determining HPC level. However, the resulting R2 value
      for a non-linear regression model that also included AOC, temperature, and pH as
      independent variables was less than 0.7. Bacterial regrowth as measured by HPC,
      is dependent upon a complex interaction of chemical, physical, and operational
      parameters that may not be captured by such a simple statistical relationship.

PMID- 11996338
TI  - The role of colloidal particles in the speciation and analysis of "dissolved"
      phosphorus.
AB  - Colloidal-sized particles (1-1,000 nm) and high molecular mass material play an
      important, yet poorly understood role in the aqueous speciation of P. This study
      assessed the size distribution of P in 0.45-microm filtered soil solutions and
      soil-water extracts from three sandy soils (grassland, arable field and forest)
      using gel filtration chromatography (GFC) and membrane filtration (0.22- and
      0.025-microm pore-size) and evaluated the impact of P speciation on colorimetric
      and ion-chromatographic methods for orthophosphate analysis. Between 40% and 58%
      of molybdate reactive P (MRP) and > 85% of molybdate unreactive P in the soil
      solution from the agricultural soils (pH 5.9-6.3) were associated with high
      molecular mass material (apparent size > 0.025 microm, or > 600 kDa on Superdex).
      In solutions from the forest soil (pH 3.2), high molecular mass P (HMMP)
      compounds were of minor importance (<8% of TP). The GFC elution profiles,
      composition and spectral characteristics of HMMP-containing solutions as well as
      the small relevance of HMMP at low pH were all indicative for associations
      between humic substances, Fe and/or Al, and P. Both MRP and ion chromatographic P
      measurements overestimated the free orthophosphate concentration (up to 2.3- and
      1.4-fold, respectively) in 0.45-microm filtered HMMP-containing solutions. In
      0.025-microm filtrates, free orthophosphate was the only MRP species present.

PMID- 11996339
TI  - An ATP luminescence method for direct toxicity assessment of pollutants impacting
      on the activated sewage sludge process.
AB  - An ATP luminescence method was used to determine the toxicity of three reference
      toxicants to two sources of domestic activated sludge, and an activated sludge
      from a laboratory model plant. Repeatability in the ATP test was demonstrated for
      Cr (as K2Cr2O7), Zn (as ZnSO4 x 7H2O), and 3,5-dichlorophenol (3,5-DCP) using
      each source of activated sludge. The three sources of sludge showed sensitivity
      to Cr and 3,5-DCP, and insensitivity to Zn using the ATP luminescence method.
      Sludge source did not appear to effect test response. The toxic response to 3,5
      DCP in model and domestic activated sludge was shown to be dependent on sludge
      solid concentration (measured as total suspended solids, gTSS(-1). It is
      recommended that a standard solids concentration is used during toxicity
      evaluation.

PMID- 11996340
TI  - Destabilisation of oil-water emulsions and separation by dissolved air flotation.
AB  - The roles of aluminium and ferric sulphates as destabilising agents for oil-water
      emulsions that have been stabilised by a non-ionic surfactant (Span 20) are
      investigated in terms of oil removal. The effects of coagulant dose, pH, and the
      duration and intensity of both slow and fast mixing are considered.
      Electrokinetic measurements indicate that oil droplets have a negative zeta
      potential that is weakly dependent on pH. The chosen coagulants are shown to be
      effective in reducing the zeta potential of the oil droplets, and charge reversal
      was observed for aluminium sulphate. Oil removals up to 99.3% at pH 8 and 99.94%
      at pH 7 are seen for aluminium sulphate and ferric sulphate respectively. Rapid
      mixing times of around 120 s and flocculation times ranging from 15 to 20 min
      appear to be optimal for the DAF separation. It is concluded that relatively low
      average mixing speeds for coagulation and flocculation are essential for
      efficient operation.

PMID- 11996341
TI  - Oxidation kinetics of phenolic and indolic compounds by ozone: applications to
      synthetic and real swine manure slurry.
AB  - In this study, an oxidation model combining the mass transfer of ozone and
      ozonation kinetics was developed to predict the degradation of several phenolic
      and indolic compounds in a semi-batch reactor. The mass transfer and partition
      coefficients were calculated at various physical and chemical conditions. In
      addition, the reaction rate constants of ozone with phenolic and indolic
      compounds were also estimated independently using the method of competition
      kinetics and relative reaction-rate constants. Incorporating mass transfer and
      chemical reaction concepts, an oxidation model that considers side reactions
      between ozone and byproducts has been established using non-linear simultaneous
      differential equations. Thus, numerical computation is capable of simulating the
      degradation of phenolic and indolic compounds both in synthetic and real manure.

PMID- 11996342
TI  - Degradation of trichloroethylene in wetland microcosms containing broad-leaved
      cattail and eastern cottonwood.
AB  - Remediation of aquifers containing trichloroethylene (TCE) relies primarily on
      physical extraction of contaminated groundwater and soil. Unfortunately, this is
      typically expensive and does not always attain the desired treatment goals. In
      situ bioremediation via natural attenuation is an alternative treatment process
      in which TCE is transformed by indigenous microorganisms and plants. In this
      study, TCE was observed in a surficial aquifer that discharges into a wetland.
      Experiments were undertaken to determine whether natural attenuation of TCE in
      the wetland was possible. Microcosms were constructed using sandy soil+/-eastern
      cottonwoods (Populus deltoides) from the wetland's edge and organic soil+broad
      leaved cattails (Typha latifolia) from the wetland's interior. [14C] TCE was
      added to each microcosm (1.27 microCi). Overtime, 14C was recovered from four
      microcosm compartments: (1) as 14C bound to soil and water, (2) as volatilized
      [14C] TCE, (3) as [14C] CO2 produced by mineralization of [14C] TCE, and (4) as
      14C incorporated into the plants. Total recoveries of the 14C-label ranged from
      73.6% to 95.8%. Volatilized [14C] TCE accounted for the majority ( > 50%) of the
      recovered label. In microcosms without plants, [14C] CO2 represented 3.2%
      (organic soil) to 15.6% (sandy soil) of the recovered 14C, indicating that TCE
      was mineralized by indigenous microorganisms. The presence of the broad-leaved
      cattail resulted in increased production of [14C] CO2 to 5.3% in the organic
      soil. The data thus suggest that natural attenuation is a potential
      bioremediative strategy for TCE-contaminated wetlands.

PMID- 11996343
TI  - Copper corrosion by-product release in long-term stagnation experiments.
AB  - The effect of long-term stagnation on copper corrosion by-product release and
      corrosion rates was studied in pipe-rigs according to the German standard DIN
      50931, Part 1. The analysis of the water phase was supplemented by surface
      analysis of corrosion scales. Copper concentration during stagnation did not
      follow a solubility process. The characteristic curves obtained can be explained
      by subsequent copper release and copper refixation processes. Oxygen consumption
      can be described by the first-order kinetic rate law. The corrosion scales
      consisted of cuprite (Cu2O) and malachite (CuCO3 x Cu(OH)2). Malachite grew in
      well-defined crystals during stagnation, served as sink for dissolved copper and
      did not protect the pipe against corrosion attack. Copper concentrations measured
      after long-term stagnation (up to 122 h) correspond to the solubility of
      malachite in the testwater.

PMID- 11996344
TI  - Assessment of efficient sampling designs for urban stormwater monitoring.
AB  - Monitoring programs for urban runoff have not been assessed for effectiveness or
      efficiency in estimating mass emissions. In order to determine appropriate
      designs for stormwater, total suspended solids (TSS) and flow information from
      the Santa Ana River was collected nearly every 15 min for every storm of the 1998
      water year. All samples were used to calculate the "true load" and then three
      within-storm sampling designs (flow-interval, time-interval, and simple random)
      and five among-storm sampling designs (stratified by size, stratified by season,
      simple random, simple random of medium and large storms, and the first m storms
      of the season) were simulated. Using these designs, we evaluated three estimators
      for storm mass emissions (mean, volume-weighted, and ratio) and three estimators
      for annual mass emissions (median, ratio, and regular). Designs and estimators
      were evaluated with respect to accuracy and precision. The optimal strategy was
      used to determine the appropriate number of storms to sample annually based upon
      confidence interval width for estimates of annual mass emissions and
      concentration. The amount of detectable trend in mass emissions and concentration
      was determined for sample sizes 3 and 7. Single storms were most efficiently
      characterized (small bias and standard error) by taking 12 samples following a
      flow-interval schedule and using a volume-weighted estimator of mass emissions.
      The ratio estimator, when coupled with the simple random sample of medium and
      large storms within a season, most accurately estimated concentration and mass
      emissions; and had low bias over all of the designs. Sampling seven storms is the
      most efficient method for attaining small confidence interval width for annual
      concentration. Sampling three storms per year allows a 20% trend to be detected
      in mass emissions or concentration over five years. These results are decreased
      by 10% by sampling seven storms per year.

PMID- 11996345
TI  - Investigation of the denitrification activity of immobilized Pseudomonas
      butanovora cells in the presence of different organic substrates.
AB  - An investigation was made of the effects of variation of the hydraulic retention
      time (HRT) and the concentrations of three different carbon sources (succinic
      acid, ethanol and acetic acid) on the denitrification activity of immobilized
      Pseudomonas butanovora cells. The highest denitrification activity was in all
      cases measured at a C: N ratio of 6: and a relatively low HRT (2.5 h). The
      highest denitrification rates were 1.17 kg NO3--N m(-3) d(-1) for succinic acid,
      1.63 kg NO3--Nm(-3) d(-1) for ethanol and 1.53kg NO3--Nm(-3) d(-1) for acetic
      acid. At the same C:N ratios, ethanol and acetic acid proved to be better
      substrates for the reduction of nitrate and nitrite. The determined optimum C: N
      ratios were 1.78 +/- 0.31, 0.95 +/- 0.17, 1.76 +/- 0.42 for succinic acid,
      ethanol and acetic acid, respectively. The optimum C:N ratios for the different
      substrates did not change in response to an increased flow rate. At a C: N ratio
      of 3:1 and a HRT of 1.5 h, the immobilized cells did not retain their activity.
      Apart from the difference in the effectivity between the electron donors, the
      main influence on the denitrification rate was exerted by the flow rate The
      results of this study demonstrated that Pseudomonas butanovora can utilize all
      three of these carbon sources to achieve a high rate of denitrification.

PMID- 11996346
TI  - Characterization and comparison of hydrophobic neutral and hydrophobic acid
      dissolved organic carbon isolated from three municipal landfill leachates.
AB  - The acid-precipitated (AP) and acid-soluble (AS) fractions of the combined
      hydrophobic neutral and hydrophobic acid dissolved organic carbon (DOC) were
      isolated from leachate collected from three municipal landfills of different age
      and redox conditions. The AP and the AS combined hydrophobic neutral and
      hydrophobic acid DOC comprised 6-15% and 51-66%, respectively, of the leachate
      nonpurgable organic carbon. Elemental analysis, infra-red spectroscopy, 13C CP
      MAS nuclear magnetic resonance spectroscopy and dipolar dephasing experiments,
      and thermochemolysis gas chromatography/mass spectrometry results showed that the
      AP and AS fractions of hydrophobic neutral and hydrophobic acid DOC are highly
      aliphatic, with linear and branching moieties, and less oxidized than most
      terrestrial and aquatic humic substances. Very little, if any, polysaccharide or
      cellulose, lignin, or cutin components comprise these fractions. It is
      hypothesized that a majority of the organic carbon in these fractions originates
      highly branched, cyclic aliphatic organic compounds.

PMID- 11996347
TI  - The influence of contact zone configuration on the flow structure in a dissolved
      air flotation pilot plant.
AB  - The dissolved air flotation process is used in water and wastewater treatment.
      Among many parameters the fluid dynamics determine the capacity of the process.
      The contact zone is assumed to be important for the removal function, as it is
      believed to be the location for the aggregation of bubbles and flocs. This paper
      presents an experimental study on the flow structure in a contact zone of a DAF
      pilot tank and the influence of contact zone configuration. The flow structure in
      the contact zone was examined for different horizontal lengths of the zone and
      for different heights and inclinations of the shaft wall. The hydraulic surface
      loading was 11 m/h over the total tank surface area and the recycle rate was
      constant at 10% of the main flow. The examined hydraulic surface loading over the
      contact zone ranged from 40 to 98 m/h. Water velocities in the longitudinal,
      central section of the tank were measured with an acoustical Doppler velocimeter
      in a grid net for the different contact zone configurations, giving an insight
      into the flow structure. The result showed that the flow structure in the contact
      zone was characterised by a turbulent lower region and a plug-flow higher region.
      The hydraulic surface loading, a function of the length of the contact zone,
      seemingly determined the extension of the turbulent region. A higher hydraulic
      surface loading decreased the turbulent region while the lower loading increased
      it. A hydraulic surface loading of 65 m/h was suggested for design. It was not
      possible to determine the turbulent intensity quantitatively due to the
      measurement method. The height and inclination of the shaft wall did not seem to
      have a significant influence on the turbulent region. However, an increased
      height of the contact zone enhanced the higher, plug flow region and a
      recommended height of 0.81 m or higher for the recommended hydraulic surface
      loading was suggested when both mixing and plug-flow are desired. The separation
      zone was characterised by a stratified flow structure, mainly influenced by the
      cross-flow velocity that is a function of the distance between the shaft wall top
      and the water surface. A cross-flow velocity of 37m/h or higher resulted in a
      clearly defined stratification, believed to be crucial for an efficient
      separation of flocs. Finally, the extension of the lower, denser plug-flow region
      in the separation zone increased when the shaft wall height increased.

PMID- 11996348
TI  - Longitudinal dispersion coefficients in natural channels.
AB  - Details are given herein, of the development of an equation for predicting the
      longitudinal dispersion coefficient in riverine flows, based on 81 sets of
      measured data, and obtained from 30 rivers in the USA. This equation relates the
      dispersion coefficient to the hydraulic and geometric parameters of the flow and
      has been derived using dimensional and regression analysis, with a high
      correlation coefficient (i.e. R2 = 0.84). The formulation has been compared with
      many other existing empirical equations, frequently used to predict the
      longitudinal dispersion coefficient in riverine flows, with the comparisons based
      on four different statistical methods. These statistical comparisons have shown
      that the new equation appears to be more accurate than the other equations
      considered. The new dispersion equation was then linearly combined with a similar
      equation recently proposed by Seo and Cheong (J. Hydraul. Eng. ASCE 124 (1998)
      25) and this combined equation was then also analysed using statistical methods.
      The existing empirical equations used to estimate the longitudinal dispersion
      coefficient and the new equations proposed in this study were included in the
      advective dispersion equation to predict the suspended sediment concentrations at
      three sites in the Humber Estuary sited along the northeast coast of England. The
      average percentage errors between the predicted- and measured-field data for the
      proposed new dispersion equations were less than those obtained using the
      previously documented equations.

PMID- 11996349
TI  - Removal of mercury(II) from aqueous solutions and chlor-alkali industry
      wastewater using 2-mercaptobenzimidazole-clay.
AB  - The 2-mercaptobenzimidazole loaded natural clay was prepared for the removal of
      Hg(II) from aqueous media. Adsorption of the metal ions from aqueous solution as
      a function of solution concentration, agitation time, pH, temperature, ionic
      strength, particle size of the adsorbent and adsorbent dose was studied. The
      adsorption process follows a pseudo-second-order kinetics. The rate constants as
      a function of initial concentration and temperature were given. The adsorption of
      Hg(II) increased with increasing pH and reached a plateau value in the pH range
      4.0-8.0. The removal of Hg(II) was found to be >99% at an initial concentration
      of 50 mg/l. Mercury(II) uptake was found to increase with ionic strength and
      temperature. Further, the adsorption of Hg(II) increased with increasing
      adsorbent dose and decrease with adsorbent particle size. Sorption data analysis
      was carried out using Langmuir and modified Langmuir isotherms for the uptake of
      metal ion in an initial concentration range of 50-1,000 mg/l. The significance of
      the two linear relationships obtained by plotting the data according to the
      conventional Langmuir equation is discussed in terms of the binding energies of
      the two population sites involved which have a widely differing affinity for
      Hg(II) ions. Thermodynamic parameters such as changes of free energy, enthalpy,
      and entropy were calculated to predict the nature of adsorption. It was found
      that the values of isosteric heat of adsorption were varied with surface loading.
      The chlor-alkali industry wastewater samples were treated by MBI-clay to
      demonstrate its efficiency in removing Hg(II) from wastewater.

PMID- 11996350
TI  - Development of a kinetic basis for bioavailability of sorbed naphthalene in soil
      slurries.
AB  - The degradation of naphthalene in soil-slurry systems was studied using four
      different organisms and two soils. Organisms with zero-order, first-order, and
      Michaelis-Menten rates were selected. The soils had substantially different
      sorption distribution coefficients. Sorption and desorption was evaluated in
      abiotic soil-slurry systems. The desorption process was described by a model that
      accounts for equilibrium, rate-limited and non-desorbing sites. Biodegradation
      parameters were measured in soil-extract solutions. Bioavailability assays,
      inoculated soil slurries, were conducted and both liquid- and sorbed-phase
      naphthalene concentrations were measured over time. For the less sorptive soil,
      the results could be explained by sequential desorption and degradation
      processes. For the other soil, enhanced degradation was clearly observed for the
      organisms with first-order and Michaelis-Menten rates. Several explanations are
      explored for these observations including direct sorbed-phase degradation and the
      development of elevated substrate concentrations at the organism/sorbent
      interface. No enhancement was found for the organism with zero-order kinetics.

PMID- 11996351
TI  - Disinfection of Bacillus subtilis spores with chlorine dioxide: a bench-scale and
      pilot-scale study.
AB  - Chlorine dioxide (ClO2) inactivation of Bacillus subtilis ATCC 19659 spores was
      examined at pilot-scale during periods representative of winter and summer
      temperature extremes at the Britannia Water Treatment Plant in Ottawa, Canada. In
      addition, bench-scale experiments using the same source water (Ottawa River,
      Ontario, Canada), as well as buffered and unbuffered laboratory waters were
      conducted using B. subtilis spores. Bench-scale inactivation of B. subtilis
      spores by ClO2 was similar to reported values for Cryptosporidium parvum (both
      organisms being more resistant to ClO2 than Giardia lamblia), suggesting the
      possibility that these spores may be used as potential indicators for protozoan
      parasites. Additionally, spore inactivation was observed to be influenced by pH
      in laboratory (distilled deionised water) water but not in Ottawa River water. At
      pilot-scale, spore inactivation was influenced by water temperature: a ClO2 dose
      of 2.5 mg/L resulted in a spore inactivation of approximately 2.0 log10 and 0.5
      log10 at water temperatures of 23.2d egrees C and 5.2 degrees C, respectively.
      Chlorite concentrations remained below both the US EPA maximum contaminant level
      of 1.0 mg/L and the maximum contaminant level goal of 0.8 mg/L for up to 2.0log10
      B. subtilis inactivation.

PMID- 11996352
TI  - The effect of drinking water treatment on the spatial heterogeneity of micro
      organisms: implications for assessment of treatment efficiency and health risk.
AB  - The effect of drinking water treatment (ferric coagulation, floc blanket
      clarification, rapid sand filtration) on the spatial heterogeneity of five
      species of micro-organism was studied at pilot scale. It was found that the
      spatial heterogeneity of vegetative bacteria (namely total coliform and
      heterotrophic (22 degrees C; 3 d) bacteria) was little affected by treatment.
      Indeed, counts of total coliform bacteria within 500 l volumes of treated water
      were Poisson distributed (i.e. showed minimum variation). In contrast, treatment
      appeared to increase the spatial heterogeneity (or clustering) of both aerobic
      spores indigenous to the raw water and Bacillus subtilis var niger spores added
      to the raw water. Furthermore, B. subtilis var niger spores added to the raw
      water were detected in the treated water 25 h after termination of spiking to the
      raw water. The effect on C. parvum oocysts added to the raw water could not be
      determined because few oocysts broke through treatment into the treated water.
      Indeed oocyst removals of 5-6 logs were apparent. "Species-specific" differences
      in the removal ratios were also demonstrated. It is concluded that audits for
      treatment processes based on single 100 ml "spot" samples for spores will tend to
      over-estimate the net spore removal and hence underestimate the public health
      risk. Spatial heterogeneity of counts in treated water contributes to explaining
      why no "ideal" surrogate has been identified for treatment plant performance.

PMID- 11996353
TI  - Comment on "experimental analysis of centrifugal dewatering process of
      polyelectrolyte flocculated waste activated sludge".
AB  - In summary, after supernatant liquid was exhausted in the author's experiments,
      menisci formed, and shrinkage, not pore evacuation and drying, was the mechanism
      causing removal of water thereafter. Results of centrifugal filtration
      experiments cannot be applied to solid bowl centrifugation because solid
      compression conditions are quite different in the two types of machines.

PMID- 11996354
TI  - Electrochemical analysis of nucleic acids at boron-doped diamond electrodes.
AB  - Highly conductive boron-doped diamond (BDD) electrodes are well suited for
      performing electrochemical measurements of nucleic acids in aqueous solution
      under diffusion-only control. The advantageous properties of this electrodic
      material in this context include reproducibility and the small background
      currents observed at very positive potentials, along with its robustness under
      extreme conditions so offering promising capabilities in future applications
      involving thermal heating or ultrasonic treatment. tRNA, single and double
      stranded DNA and 2'-deoxyguanosine 5'-monophosphate (dGMP) have been studied and
      well defined peaks were observed in all cases, directly assignable to the electro
      oxidation of deoxyguanosine monophosphate.

PMID- 11996355
TI  - Coumarins give misleading absorbance with Ellman's reagent suggestive of thiol
      conjugates.
AB  - In the course of a screening for phytochelatins in cadmium-exposed bryophytes in
      the terrestrial mosses Polytrichum formosum and Atrichum undulatum we detected
      compounds with absorption properties and retention times similar to
      phytochelatins when applying the commonly used standard method RP-HPLC and post
      column derivatization with thiol-specific DTNB (Ellman) reagent. Moreover, as
      with phytochelatins known in other plants, the concentrations of these compounds
      increased slightly after Cd stress. The concentration of the precursor
      glutathione (gamma-ECG), however, increased in the presence of Cd. In order to
      verify the identity of these putative phytochelatins we performed LC-ESI-MS
      analyses as well as 1H NMR on extracts from P. formosum and A. undulatum.
      Spectroscopic investigations indicated that the detected compounds were neither
      phytochelatins nor other thiol compounds. From the results of HPLC-1H NMR and
      mass spectrometry we concluded that at least one of these substances was a
      coumarin, probably a 5,8-dihydroxy-7-methoxycoumarin-5-beta-glucopyranoside,
      which has already been described for A. undulatum and P. formosum. The results of
      our investigations prove that under the basic pH conditions essential for the
      Ellman test for thiol compounds, coumarins show comparable UV/VIS absorption
      properties. Therefore, a positive post-column Ellman reaction cannot
      unambiguously prove the presence of thiol-containing compounds in plants.

PMID- 11996356
TI  - Nonlinear electrophoresis of protein-detergent complexes.
AB  - A comparatively new procedure is described for the nonlinear electrophoresis of
      proteins. Movement and separation of complexes formed by proteins and ionic
      detergents is first experimentally demonstrated for SDS rainbow colored protein
      molecular weight markers (Amersham). This result was revealed by SDS-PAGE in an
      asymmetric zero average pulsed electric field with a peak amplitude of up to 300
      V cm(-1) and a frequency of 100 Hz. The highest molecular weight fractions were
      found to have the highest nonlinear drift velocity. A two-dimensional map of
      distribution of the protein complexes developed using nonlinear electrophoresis
      followed by SDS gel electrophoresis in an orthogonal direction, reveals
      nonuniform distribution of the fractions. Nonlinear electrophoresis can be run
      without electrode chambers, since the buffer electrolyte is not used up in
      alternating electric fields. Thus, this new type of electrophoresis can have
      advantages in microfluidic systems and biochips. Also possible uses are discussed
      of nonlinear electrophoresis via nonlinear focusing of protein-detergent
      complexes for further improvement of the SDS-PAGE technique for the separation
      and examination of these large hydrophobic complexes.

PMID- 11996357
TI  - Development and validation of an improved method for confirmation of the carbadox
      metabolite, quinoxaline-2-carboxylic acid, in porcine liver using LC-electrospray
      MS-MS according to revised EU criteria for veterinary drug residue analysis.
AB  - A method is described for the quantitative determination of quinoxaline-2
      carboxylic acid (QCA), the marker residue for the veterinary drug carbadox, in
      swine liver. Tissue is subjected to alkaline hydrolysis followed by liquid-liquid
      extraction. QCA residues are cleaned up using automated solid phase extraction
      (SPE), before a final liquid-liquid extraction step. Analysis is based on LC
      coupled to positive ion electrospray MS-MS, monitoring product ions at m/z 129,
      102 and 75 for QCA and at m/z 106 for the internal standard (d4-QCA). The method
      has been validated according to draft revised EU criteria for analysis of
      veterinary drug residues, and is suitable for monitoring tissues taken under
      national surveillance schemes. The method has been validated at 3, 10, 30, 100
      and 300 microg kg(-1). The method performance characteristics, CCalpha (decision
      limit) and CCbeta (detection limit) were determined to be 0.16 and 0.27 microg
      kg(-1), respectively. The described method, which is relatively rapid and
      applicable to large sample numbers, correlates well (r2 = 0.9799) with a widely
      used GC-MS assay for QCA.

PMID- 11996358
TI  - Multiresidue method for the analysis of multiclass pesticides in agricultural
      products by gas chromatography-tandem mass spectrometry.
AB  - A multiresidue method is described for determining 55 organophosphorus and
      organochlorinated compounds and pyrethroids commonly used in crop protection.
      Pesticide residues are extracted from samples with a mixture of ethyl acetate and
      sodium sulfate, obtaining a final preconcentration of I mg sample (ml extract)(
      1). No additional clean-up steps are necessary. Analysis is performed by gas
      chromatography by using a combination of positive chemical ionisation (PCI) and
      electron impact (EI) ionisation modes and tandem mass spectrometry (GC-PCI/EI-MS
      MS). Good sensitivity and selectivity of the method are obtained with limits of
      detection (LODs) ranging from 0.07 to 4.21 microg kg(-1) in all the cases, except
      for methamidophos, permethrin, cypermethrin and difenconazol. Average recoveries
      between 52 and 114% are obtained and good linearity is observed in the studied
      ranges (r > or = 0.994). The RSD values are < or = 29% in all the cases. The
      method has been applied to the analysis of 178 vegetable samples, as a part of
      the monitoring programme of the Association of Producers and Exporters of Fruits
      and Vegetables of Almeria (COEXPHAL) and quality control systems applied during
      the assays have demonstrated a good performance and stability with time.

PMID- 11996359
TI  - Non-equilibrium solid-phase microextraction coupled directly to ion-trap mass
      spectrometry for rapid analysis of biological samples.
AB  - To determine sub-ppb levels of drugs in biological samples, selective, sensitive
      and rapid analytical techniques are required. This work shows the possibilities
      for high-throughput analysis of solid-phase microextraction (SPME) directly
      coupled to an ion-trap mass spectrometer equipped with an atmospheric pressure
      chemical ionisation source. As no chromatographic separation is performed, the
      SPME procedure is the time-limiting step. Direct immersion SPME under non
      equilibrium conditions permits the determination of lidocaine in urine within 10
      min. After a 5 min sorption time with a 100 microm polydimethylsiloxane-coated
      fibre, the extraction yield of lidocaine from urine is about 7%. When applying 4
      min desorption, using a mixture of ammonium acetate buffer (pH 4.5) and
      acetonitrile (85 + 15 v/v), about 10% of the analyte is retained on the fibre. An
      extra cleaning step of the fibre is therefore used to prevent carry-over. By use
      of tandem MS, no matrix interference is observed. The detection limit for
      lidocaine is about 0.4 ng ml(-1) and the intraday and interday reproducibility
      are within 14% over a concentration range of 2-45 ng ml(1).

PMID- 11996360
TI  - Real-time monitoring of stain formation and removal on calcium hydroxyapatite
      surfaces using quartz crystal sensor technology.
AB  - Stain formation, stain inhibition and stain removal may be monitored in real-time
      using a novel method employing a quartz crystal resonance sensor (QCR), based
      upon quartz crystal microbalance (QCM) technologies. Crystalline hydroxyapatite
      (HA) surfaces were prepared on phosphate-terminated, polymer-modified gold
      surfaces of quartz crystal transducers. The resulting sensors were placed in a
      specially constructed flow cell, and the interaction of adsorbates from the tea
      stain solution monitored as a function of time. The ability of sodium
      tripolyphosphate (STP) to remove extrinsic stain and also to inhibit its
      formation was examined. The adsorption of material from the staining solution
      passed over the sensor was clearly observable, and once bound, the crystal based
      real-time data suggest that tea adsorbates were not removed in the absence of an
      active under conditions of continuous flow. STP was shown to rapidly remove
      existing stain, and exhibited a clear inhibitory action on stain formation
      irrespective of whether the HA had been previously exposed to tea chromogens. The
      continuous data generated by the QCR technique were in good agreement with the
      results obtained using a discontinuous spectrophotometric method. The presently
      described quartz crystal model for extrinsic dental stain should provide a
      valuable tool to aid understanding of the interactions of staining agents with a
      crystalline HA surface as a model tooth surface, and to evaluate the efficacy and
      mode of action of STP and putative stain removal agents.

PMID- 11996361
TI  - Determination of 4-aminophenol using the quartz crystal microbalance sensor.
AB  - In this paper we report a method for the determination of 4-aminophenol (4-AP) in
      solution using a quartz crystal microbalance (QCM) sensor. 4-AP reacts with (para
      unsubstituted) phenols to form hydrophobic indophenol dye species that
      precipitate out and adsorb to the surface of the crystal to produce a shift in
      the crystal resonant frequency. This frequency change, due to in-situ indophenol
      mass adsorption, can be related to the initial 4-AP concentration. A range of
      phenols (namely o-cresol, 1-naphthol, resorcinol, catechol and 8
      hydroxyquinoline) and their reaction with 4-AP were tested. Ammonium persulfate
      (APS) and potassium periodate were used as initiators to improve the speed of the
      reaction and the rate of formation of the precipitate. APS elicited improved
      signal in terms of response times and frequency shifts compared with KIO4. Of the
      phenols studied, resorcinol gave the best response time of 6 min for 4-AP
      determination. The reaction of resorcinol with 4-AP gave extended response times
      and signal size with decreasing concentration of 4-AP (in the range 2-5 mM).

PMID- 11996362
TI  - Effect of static magnetic field on growth of Escherichia coli and relative
      response model of series piezoelectric quartz crystal.
AB  - The effect of magnetic field on the growth of bacteria was studied with the
      series piezoelectric quartz crystal (SPQC) sensing technique. The growth
      situations of Escherichia coli (E. coli) in the absence and presence of different
      intensities of static magnetic fields were examined and analyzed. The results
      showed that the growth of E. coli was inhibited due to the presence of magnetic
      fields. By fitting frequency shift (deltaD) versus time curves according to the
      frequency shift response equation of SPQC, the relationships between three
      kinetic growth parameters, i.e., the asymptote A, the maximum specific growth
      rate mu(m) and lag time lambda, and magnetic field intensity were established.
      Based on these results, a new response model containing the magnetic field
      intensity was derived as: delta(f) = 167.7 (7.25 - 7.11B)/[1 + exp[4 x 2.46e(
      3.97B)/(7.25 -7.1 IB)] x (4.42 + 16.46B - t) + 2]] The kinetic parameters of
      bacterial growth obtained from this model are close to those obtained from the
      logistics popular growth model, in which the concentration of the bacteria was
      determined by the traditional pour plate count method.

PMID- 11996363
TI  - Asymmetric anti-resonant reflecting optical waveguides (arrow) as chemical
      sensors.
AB  - Anti-resonant reflecting optical waveguides (ARROW) are described which trap
      light in a low index layer between a lower, high-index confining layer and an
      upper total internal reflection boundary. In this configuration, most of the
      light (greater than 80%) travels in the low index porous polymer layer, the
      refractive index of which is monitored by examining the angle at which light is
      coupled out of the waveguide. It is shown that asymmetric ARROW sensors can be
      constructed using conventional chemical vapour deposition and spin-coating
      techniques and their sensitivity is as predicted by theoretical modelling.

PMID- 11996364
TI  - Amplified label-free electrical detection of DNA hybridization.
AB  - A new protocol is described for amplifying label-free electrochemical
      measurements of DNA hybridization based on the enhanced accumulation of purine
      nucleobases in the presence of copper ions . Such electrical DNA assays involve
      hybridization of the target to inosine-substituted oligonucleotide probes
      (captured on magnetic beads), acidic dipurinization of the hybrid DNA, and
      adsorptive chronopotentiometric stripping measurements of the free nucleobases in
      the presence of copper ions. Both amplified adenine and guanine peaks can be used
      for detecting the DNA hybridization. The dramatic signal amplification advantage
      of this type of detection has been combined with efficient magnetic removal of
      non-complementary DNA, use of microliter sample volumes and disposable
      transducers. Factors influencing the signal enhancement were assessed and
      optimized. A detection limit of 40 fmol (250 pg) was obtained with 10 min
      hybridization and 5 min adsorptive-accumulation times. The advantages of this
      procedure were demonstrated by its application in the detection of DNA segments
      related to the BRCA1 breast cancer gene. The copper enhancement holds great
      promise not only for the detection of DNA hybridization, but also for trace
      measurement of nucleic acids.

PMID- 11996365
TI  - A perchlorate-selective membrane electrode based on a Cu(II) complex of the
      ligand 1,4,8,11-tetra(n-octyl)-1,4,8,11-tetraazacyclotetradecane.
AB  - The new cyclic polyazacycloalkane 1.4,8,11-tetra(n-octyl)-1,4,8,11
      tetraazacyclotetradecane (L1) was synthesised and the copper(II) complex
      [Cu(L1)]2+ characterised. Different electrodes were prepared using the [Cu(L1)]2+
      complex as ionophore, PVC as plastic matrix and o-nitrophenyl octyl ether (NPOE),
      bis(2-ethylhexyl) sebacate (BEHS) or dibutyl phthalate (DBP) as plasticizers. The
      electrode containing DBP showed a Nernstian response over a wide pH range and a
      fast response time (ca. 3 s) whereas NPOE and BEHS gave near-Nernstian slopes.
      Selectivity coefficients for the different anions with respect to perchlorate
      were calculated. The response of the electrodes basically followed the Hofmeister
      sequence, suggesting that interaction of the ionophore with the anions is via
      electrostatic forces rather than due to anion coordination to the axial sites of
      the square-planar [Cu(L1)]2+ complex.

PMID- 11996366
TI  - Renewable urea sensor based on a self-assembled polyelectrolyte layer.
AB  - A renewable urea sensor based on a carboxylic poly(vinyl chloride) (PVC-COOH)
      matrix pH-sensitive membrane has been proposed, in which a positively charged
      polyelectrolyte layer is first constructed by using a self-assembly technique on
      the surface of a PVC-COOH membrane, and urease, with negative charges, is then
      immobilized through electrostatic adsorption onto the PVC-COOH membrane, by
      controlling the pH of the urease solution below its isoelectric point. The
      response characteristics of the PVC-COOH pH-sensitive membrane and the effects of
      experimental conditions have been investigated in detail. Compared with
      conventional covalent immobilization, the urea sensor made with this self
      assembly immobilization shows significant advantage in terms of sensitivity and
      ease of regeneration. The potential responses of the urea sensor with self
      assembly immobilization increase with the urea concentration over the
      concentration range 10(-5) - 10(-1) mol l(-1), and the detection limit is 0.028
      mmol(-1). Moreover, this type of urea sensor can be repeatedly regenerated by
      using a simple washing treatment with 0.01 mol l(-1) NaOH (containing 0.5 mol l(
      1) NaCl) and 0.01 mol l(-1) HCl. The urease layers and the polyelectrolyte layers
      on the PVC-COOH membrane are removed, the potential response of the sensor to
      urea solutions of different concentrations returns nearly to zero, and another
      assembly cycle of urease and polyelectrolyte can then be carried out.

PMID- 11996367
TI  - The study of nafion/xanthine oxidase/au colloid chemically modified biosensor and
      its application in the determination of hypoxanthine in myocardial cells in vivo.
AB  - A novel hypoxanthine (Hx) microsensor was constructed. In this work, Nafion
      xanthine oxidase (XOD) and Au colloid were immobilized onto the surface of a Pt
      microelectrode. The enzyme biosensor displayed a quick and sensitive response to
      Hx. Under physiological conditions, a low detection limit, with high selectivity
      and sensitivity for Hx determination were obtained. The oxidation current
      [investigated using current-time (I-t) plots] was linear with Hx concentration
      ranging from 2.0 x 10(-7) to 2.0 x 10(-5) mol L(-1) with a calculated detection
      limit of 1.0 x 10(-7) mol L(-1) (S/N of 3). The biosensor should be promising for
      in vivo measurement of Hx without interferences and fouling. The change of Hx
      concentration in cardiac myocytes stimulated by L-arginine (L-Arg) and
      acetylcholine (Ach) was also studied.

PMID- 11996368
TI  - Study of Cd2+ complexation by the glutathione fragments Cys-Gly (CG) and gamma
      Glu-Cys (gamma-EC) by differential pulse polarography.
AB  - A differential pulse polarographic study of the Cd2+/gamma-Glu-Cys and Cd2+/Cys
      Gly systems assisted by the alternating least-squares multivariate curve
      resolution (MCR-ALS) method was carried out to obtain a better understanding of
      the different metal affinities of the complexation sites on glutathione (GSH).
      The simultaneous analysis of the titration of peptide with metal and of metal
      with peptide allowed the resolution of the Cd2+/Cys-Gly system, whereas in the
      analysis of the Cd2+/gamma-Glu-Cys system the analysis of a single titration
      experiment was sufficient. The analysis of the shape of the resulting pure
      voltammograms and concentration profiles of the resolved components suggested the
      presence of two different types of bound Cd2+ in the two systems considered, that
      could be attributed to Cd2+ bound to one or two sulfur atoms to form complexes of
      stoichiometry 1:1 and 1:2. respectively.

PMID- 11996369
TI  - Proton nuclear magnetic resonance characterisation of glycosaminoglycans using
      chemometric techniques.
AB  - Various types of glycosaminoglycans (GAGs) including heparins, chondroitin
      sulfates, dermatan sulfate and hyaluronic acid were studied from their proton
      nuclear magnetic resonance (1H NMR) spectra using chemometric techniques. Despite
      the complexity of the 1H NMR signals, data analysis using principal component
      analysis enabled the different GAG classes to be distinguished and permitted
      their classification according to their chemical structure. The analysis of the
      composition of the major disaccharide unit and other relevant chemical structures
      in the heparin samples was performed using partial least squares regression.

PMID- 11996370
TI  - Determination of copper and zinc in serum by derivative atomic absorption
      spectrometry using the microsampling technique.
AB  - A method has been developed for the determination of copper and zinc in the serum
      of rats by derivative microsampling flame atomic absorption spectrometry (D
      MFAAS). The microsampling volume, solution uptake rate and other figures of merit
      of the proposed methodology were studied. For a 100 microl volume, the
      characteristic concentrations and detection limits (3s) of D-MFAAS were 0.023 and
      0.013 microg ml(-1) for copper and 0.0066 and 0.0080 microg ml(-1) for zinc,
      which were 4.5-6.5-fold better than those of microsampling flame atomic
      absorption spectrometry (MFAAS). The detection limits and sensitivities of D
      MFAAS were 6.4- and 16-fold for 300 microl volume for copper, 14- and 13-fold for
      250 microl volume for zinc, better than those of MFAAS. The method demonstrates
      high tolerance to interferences, and the analytical results obtained for a
      certified reference material, GBW 08551 Pork Liver, were in good agreement with
      the certified values. The recovery with the standard additions method was good,
      in the range 97.6-101.5%, and precisions (relative standard deviations) obtained
      for a diluent sample containing 0.5 microg ml(-1) copper and 0.7 microg ml(-1)
      zinc were 4.0% and 3.5% (n = 15) for copper and zinc, respectively.

PMID- 11996371
TI  - Flow injection determination of readily assimilable nitrogen compounds during
      vinification.
AB  - A flow injection method for the determination of readily assimilable nitrogen
      (r.a.n.), i.e. ammonium and aminated nitrogen, is reported. The difference in pH
      of the sample in the presence and absence of formaldehyde, which blocks the amino
      function, provides the value of r.a.n. by monitoring the changes in absorbance of
      bromothymol blue at 616 nm. The detection and quantification limits are 10 and
      11.6 mg l(-1), respectively, the reproducibility and repeatability are 3.94 and
      1.35 mg l(-1), respectively, and the sample throughput is 20 samples h(-1). The
      method has been applied to the analysis of 120 samples of must and wine subjected
      to biological aging. The proposed method also provides good correlation with the
      reference method used in routine analysis, and is faster

PMID- 11996372
TI  - Monitoring the removal of carbonate from alkali metal hydroxide solutions using
      gas diffusion flow injection.
AB  - Monitoring the removal of carbonate from alkali metal hydroxide (MOH, M = K, Na)
      solutions with calcium oxide (CaO) was studied using a newly developed method for
      the determination of trace amounts of total carbonate (TC) in alkaline solutions
      based on a flow injection (FI) technique coupled with a gas diffusion system. The
      optimized conditions of the FI system were as follows: the flow rate of each
      carrier, reaction solution (H2SO4) and receptor solution (Cresol Red, pH 8.9) was
      0.25 ml min(-1), the sample size was 0.1 ml and the concentration of H2SO4 in the
      reaction solution was 0.09 M. The limit of detection of TC by the proposed method
      was 4 x 10(-7) M. The removal efficiency of carbonate was affected by the amount
      of CaO added, the shaking time of the solutions and the concentration of MOH. For
      1 M NaOH and KOH solution, the removal efficiency of carbonate was about 99% and
      the concentration of residual carbonate was 4 x 10(-5) and 1.2 X 10(-4) M,
      respectively, when the amount of CaO added was 2 g l(-1) and the shaking time was
      16 h.

PMID- 11996373
TI  - Report by the analytical methods committee. Application of gas-liquid
      chromatography to the analysis of essential oils. Part XVIII. Determination of
      safrole in oils of cinnamon leaf, Litsea cubeba, and nutmeg.

PMID- 11996374
TI  - Polychlorinated biphenyl occurrence in American alligators (Alligator
      mississippiensis) from Louisiana and South Carolina.
AB  - Few studies have evaluated PCB concentrations in alligators. This is the first
      comparison of PCB concentrations in alligators eggs from the southeastern United
      States. Eggs were collected from Bear Island and Winyah Bay, South Carolina and
      from the Rockefeller Wildlife Refuge, Louisiana. Mean PCB concentrations in eggs
      from Bear Island (333 ng/g) were the same (P > 0.45) as those found at the
      Rockefeller Wildlife Refuge (218 ng/g). However, eggs from Winyah Bay contained
      3176 ng/g PCBs which is higher (P < 0.008) than concentrations from the other two
      sites. These data indicate the ubiquitous nature of PCBs and their
      bioaccumulation even in remote habitats.

PMID- 11996375
TI  - Contamination by polycyclic aromatic hydrocarbons in the Jiulong River Estuary
      and Western Xiamen Sea, China.
AB  - The distribution of 16 polycyclic aromatic hydrocarbons (PAHs) was determined in
      water, sediment and pore water of the Jiulong River Estuary and Western Xiamen
      Sea, China. Total PAH concentrations varied from 6.96 to 26.9 microg/l in water,
      59-1177 ng/ g dry weight in surficial sediments, and 158-949 microg/l in pore
      water. The PAHs were present in higher levels in pore water than in surface
      water, due possibly to higher concentrations of dissolved organic carbon or
      colloids with which the hydrophobic pollutants were strongly associated. Such a
      concentration gradient implies a potential flux of pollutants from sediment pore
      water to overlying water. The levels of PAHs in water and pore water were
      significantly higher than those found in 1998, suggesting recent inputs of these
      compounds into the area and re-working of sediment phase. The composition pattern
      of PAHs in the three phases was dominated by high molecular weight PAHs, in
      particular 5-ring PAHs. The salinity profile of dissolved PAHs suggested that
      they all behaved non-conservatively due to deviation from the theoretical
      dilution line. No correlation was found between PAH concentrations in sediment
      and those in pore water, and the correlation between the partition coefficients
      of PAHs and sediment organic carbon content was not significant, suggesting the
      complexity of the partition behaviour of PAHs. As a result of high PAH
      concentrations in water and pore water, it is likely that they may have caused
      mortality to certain exposed organisms.

PMID- 11996376
TI  - Assessing the biological status of fish in a river receiving pulp and paper mill
      effluents.
AB  - This study compared the use of sentinel species- and community-based field
      approaches for assessing the biological status of fish living in a river
      receiving pulp and paper mill effluents. Three approaches were compared. Two
      approaches used sentinel species. One of these involved an internal/external
      examination of the fish that leads to the calculation of a fish health assessment
      index (HAI) and the other involved biochemical measurements of hepatic mixed
      function oxidase (MFO) activity and plasma steroid levels. The third approach
      characterized the fish community structure according to an index of biotic
      integrity (IBI). The comparison focused on how the methods respond to the
      hypothesis that recent process modifications/effluent treatment changes,
      resulting in demonstrable improvements in effluent quality, have beneficial
      effects on fish. Neither of the approaches using sentinel fish indicated clear
      mill-related influences either before or after the process modifications/effluent
      treatment changes. There was no evidence of depressed plasma steroids and
      increased MFO activity in fish frequently associated with mill effluent exposure
      in previous studies. While the HAI was higher at stations downstream from two
      mills, this could not be linked to effluent exposure alone. In contrast, the
      study of community structure showed a substantial improvement in fish assemblages
      at all the mill sites.

PMID- 11996377
TI  - MTBE and aromatic hydrocarbons in North Carolina stormwater runoff.
AB  - A total of 249 stormwater samples were collected from 46 different sampling
      locations in North Carolina over an approximate 1-year period and analyzed to
      identify land use types where fuel oxygenates and aromatic hydrocarbons may be
      present in higher concentrations and at greater frequency. Samples were analyzed
      by gas chromatography-mass spectrometry in ion selective mode to achieve a
      quantitation limit of 0.05 microg/l. m-,p-Xylene and toluene were detected in
      over half of all samples analyzed, followed by MTBE: o-xylene: 1,3,5
      trimethylbenzene: ethylbenzene; and 1,2,4-trimethylbenzene. Benzene, DIPE, TAME
      and 1,2,3-trimethylbenzene were detected in < 10% of the samples analyzed. Median
      contaminant concentrations (when detected) varied from 0.07 microg/l for
      ethylbenzene to 0.11 microg/l for toluene. All of the locations with
      significantly higher contaminant concentrations were associated with direct
      runoff from a gas station or discharge of contaminated groundwater from a former
      leaking underground storage tank. For all of the aromatic hydrocarbons, the
      maximum observed contaminant concentrations were over an order of magnitude lower
      than current drinking water standards.

PMID- 11996378
TI  - Distribution of trace metals in moss biomonitors and assessment of contamination
      sources in Portugal.
AB  - A biomonitoring survey using the moss species [Hypnum cupressiforme Hedw. and
      Scelopodium touretii (Brid.) L. Kock] was performed in the whole territory of
      Portugal, in order to evaluate the atmospheric deposition of the following
      elements: Cd. Cr, Cu, Fe, Mn, Ni, Pb and Zn. The concentrations of the same
      elements were also obtained in two types of soil samples, collected under the
      moss and in nearby plots without any plant coverage, and relationships between
      moss and soil concentrations was investigated using the multivariate statistical
      method of Co-inertia Analysis. Also, relationships between concentrations in moss
      and several anthropogenic, geologic, pedologic and environmental parameters were
      screened using the same method of Co-inertia Analysis. Higher concentrations of
      Cu, Pb and Zn were found in areas of higher population density, with higher
      gasoline consumption, while higher values of Fe and Cr occur in the driest
      region, with lower plant coverage, indicating strong contamination by resuspended
      soil particles. Results also show good agreement between moss and soil contents,
      even for elements with high contribution of anthropogenic sources. The spatial
      pattern in Portugal of element contents in mosses were also detected and
      discussed in relation to local contamination sources.

PMID- 11996379
TI  - Response of fluctuating asymmetry to arsenic toxicity: support for the
      developmental selection hypothesis.
AB  - The effect of exposure to sodium arsenite during development was tested on adult
      fluctuating asymmetry (FA) in sternopleural bristle number, bristle number, body
      size and survivorship in Drosophila melanogaster. Three genetic strains of flies
      were used, CT-106, PVM and Oregon-R, and arsenite concentrations ranged from
      relatively mild, sub-lethal doses, to concentrations with pronounced negative
      effects on survivorship. At arsenite concentrations of 1.0 and 0.125 mM,
      mortality was on average 38% greater than in controls, and surviving flies
      emerged significantly smaller and had fewer bristles than controls. Neither the
      effect of arsenite or the genotype x environment interaction on asymmetry were
      significant. However, given the high mortality, any increase in FA could have
      been masked by the outcome of developmental selection against developmentally
      unstable phenotypes. We tested for this effect by contrasting FA values between
      (1) flies reared at the highest concentrations used previously, (2) flies reared
      at sub-lethal dosage, and (3) controls. Positional fluctuating asymmetry (PFA),
      which is expected to be a sensitive indicator of underlying developmental
      stability, was significantly reduced among flies reared at the highest
      concentration, and at which flies suffered significant mortality. Moreover, the
      slope of the regression relating mean PFA to emergence per bottle was
      significantly positive. These data support the hypothesis that developmental
      selection occurred in this experiment, and that the expected positive
      relationship between asymmetry and stress may be altered when the stressor
      eliminates individuals from the population. In contrast, FA of flies reared at
      sub-lethal dosage did not differ from that in controls, a result that fails to
      support the hypothesis that arsenite disrupts developmental stability. Our
      results call for caution in FA-based biomonitoring, especially of potentially
      lethal forms of stress, because in the presence of developmental selection, and
      under the common assumption that FA should increase under stress, erroneous
      conclusions may be drawn about the health and well being of a population. It is
      suggested that FA-based biomonitoring efforts integrate the use of FA with other
      bioindicators, and experimentally validate any expected FA-stress relationship
      before attempting to infer the presence of environmental stress.

PMID- 11996380
TI  - Body burdens and tissue concentrations of organochlorines in polar bears (Ursus
      maritimus) vary during seasonal fasts.
AB  - Lipophilic organochlorines (OCs) are ingested by mammals through their foods and
      are generally stored in adipose tissue depots. For some species, such as polar
      bears, the size of these depots can fluctuate seasonally by several-fold.
      However, the effect of these fluctuations on the fate of stored OCs in an animal
      with such labile lipid depots is unknown. We determined the whole body burden and
      tissue concentrations of OCs in free-ranging polar bears categorized by age (cubs
      of-the-year, yearlings and adults) and sex before and after a fast averaging 56
      days. Adipose tissue, plasma, and milk samples were analysed for sum of
      chlorobenzenes (sigma-ClBzs), hexachlorocyclohexanes (sigma-HCHs), chlordanes
      (sigma-CHLORs), dichlorodiphenyltrichloroethane compounds (sigma-DDTs) and
      polychlorinated biphenyls (sigma-PCBs). Decline in body mass during fasting
      ranged from 0.2 kg/day for cubs-of-the-year to 0.9 kg/day for sub-adult and adult
      males. Although all bears showed a decline in both lipid and lean mass during
      fasting, patterns of OC whole body burden changes were not consistent among
      compounds and bear classes. The burdens of sigma-DDTs declined by 11-50% for most
      bears during fasting, those of sigma-CHLORs declined by 67% during fasting in sub
      adult and adult males but remained constant for all females, indicating male
      specific metabolism of sigma-CHLORs. As fat depots became depleted, OC
      concentrations in the remaining adipose tissue varied; sigma-DDTs and sigma-HCHs
      declined while those of sigma-CHLORs and sigma-PCBs generally increased. Thus.
      within a 3-4 month fast, most polar bears were able to significantly rid their
      adipose tissue of sigma-DDTs and sigma-HCHs. Burdens of sigma-CHLORs (except
      males), sigma-ClBzs and sigma-PCBs remained constant for all classes of bears,
      therefore there was no significant excretion or metabolism during the fast of the
      specific congeners in these compound classes typically found in polar bears. The
      ratio of plasma/adipose tissue and milk/adipose tissue OC concentrations was the
      same for before and after the fast indicating that OC concentrations in polar
      bears are probably at a steady state among various body compartments.
      Concentrations of sigma-CHLORs and sigma-PCBs in milk almost doubled during the
      fast. As a consequence of this rise in milk OC concentrations, the whole body
      concentrations of these compounds increased in nursing cubs. Since developing
      young may be susceptible to the effects of environmental contaminants, the
      increased exposure of nursing cubs to OCs during a fast by their mothers is
      noteworthy.

PMID- 11996381
TI  - Metals in airborne particulate matter from the first and second industrial
      complex area of Taejon city, Korea.
AB  - To understand the metal distribution characteristics in a rapidly urbanized area,
      we collected and analyzed particulate matter (PM) samples for the metal
      concentrations. Using our measurement data for various metal species, we examined
      both the extent of metal pollution in the study area and the seasonality in their
      distribution characteristics. Results showed that each metal exhibited their
      occurrences in diverse concentration ranges over several orders of magnitude such
      as the mean values ranging from minimum value of 0.07 (Be) to maximum value of
      1633 ng m(-3) (Fe). In addition, the extent of metal pollution in the study area
      was in general comparable with those typically observed from a strongly polluted
      urban area, if comparison was made with the results of previous studies.
      Examinations of their temporal distribution patterns indicated that most of
      metals tend to exhibit seasonal peaks during winter (or spring) seasons,
      similarly to the observed pattern for PMs. Moreover to explain the factors
      regulating their mobilization properties, the data were analyzed through the
      application of correlation analysis. Results of our correlation analysis showed
      that most metals can exhibit strong positive correlations each other, while they
      tend to be inversely correlated with most of important meteorological parameters
      (including air temperature and precipitation). Based on the overall results of
      our study, we conclude that the site may be strongly impacted by man-made sources
      but that many characteristics of their cycling are not significantly different
      from those generally observed from natural environments.

PMID- 11996382
TI  - Cadmium accumulation and metallothionein synthesis in freshwater bivalves
      (Pyganodon grandis): relative influence of the metal exposure gradient versus
      limnological variability.
AB  - The relative influence of limnological confounding factors on cadmium (Cd)
      bioaccumulation and metallothionein (MT) synthesis was quantified in natural
      populations of freshwater bivalves (Pyganodon grandis) living in lakes along a Cd
      concentration gradient. During the ice-free period, we measured 15 environmental
      variables in the water compartment and determined total concentrations of Cd and
      MT in the gills of bivalves at 37 littoral stations in 20 lakes distributed
      across the mining area of Rouyn-Noranda in northwestern Quebec. A multiple linear
      regression model including pH (+), dissolved Ca concentrations (-) and free Cd2+
      concentrations at the sediment-water interface (+) explained 74% of the
      variability in Cd concentrations in the bivalve gills. Dissolved Ca (-) and free
      Cd2+ (+) together explained 62% of the variation in MT concentrations in the
      bivalve gills. Partial linear regression analyses indicated that the limnological
      factors' pure and shared effects together accounted for 48 and 45% of the total
      variation in Cd and MT concentrations in the gills, respectively. A lake
      selection procedure that could be applied in monitoring programs is proposed to
      minimise the relative influence of these confounding variables.

PMID- 11996383
TI  - Effects of atmospheric pollution on lichen biodiversity (LB) in a Mediterranean
      region (Liguria, northwest Italy).
AB  - The effects of air pollution on lichen biodiversity (LB) were monitored in
      Liguria (northwest Italy). A systematic sampling strategy was adopted in order to
      avoid the influence of spatial autocorrelation on the results. An eight LB class
      scale permitted to point out the levels of naturality/alteration in the region.
      The comparison of these results with the ones obtained by mean of physico
      chemical methodologies shows a good accordance. The results of this study suggest
      the possibility of designing an integrated monitoring network, in which
      biological monitoring will allow to estimate the level of alteration in remote
      areas, which account for most of this region and which are currently not covered
      by measurements with automatic systems.

PMID- 11996384
TI  - Induction of PAH-catabolism in mushroom compost and its use in the biodegradation
      of soil-associated phenanthrene.
AB  - This paper describes the induction of phenanthrene-catabolism within Phase II
      mushroom compost resulting from its incubation with (1) phenanthrene, and (2) PAH
      contaminated soil. Respirometers measuring mineralization of freshly added 14C-9
      phenanthere were used to evaluate induction of phenanthrene-catabolism. Where
      pure phenanthrene (spiked at a concentration of 400 mg kg(-1) wet wt.) was used
      to induce phenanthrene-catabolism in compost, induction was measurable, with
      maximal mineralization observed after 7 weeks phenanthrene-compost contact time.
      Where PAH-contaminated soil was used to induce phenanthrene-catabolism in un
      induced compost, induction was observed after 5 weeks soil-compost contact time.
      Microcosm-scale amelioration of soil contaminated with 14C-phenanthrene (aged in
      soil for 516 days prior to incubation with compost) indicated that both induced
      (using pure phenanthrene) and uninduced Phase II mushroom composts were equally
      able to promote degradation of this soil-associated contaminant. After 111 days
      incubation time, 42.7 +/- 6.3% loss of soil-associated phenanthrene was observed
      in the induced-compost soil mixture, while 36.7 +/- 2.9% loss of soil-associated
      phenanthrene was observed in the uninduced-compost soil mixture. These results
      are notable as they indicate that while pre-induction of phenanthrene-catabolism
      within compost is possible, it does not significantly increase the extent of
      degradation when the compost is used to ameliorate phenanthrene-contaminated
      soil. Thus, compost could be used directly in the amelioration of contaminated
      land i.e. without pre-induction of catabolism.

PMID- 11996385
TI  - Atmospheric deposition and ionic interactions within a beech canopy in the
      Karkonosze Mountains.
AB  - A method, of artificial foliage placed above rain collectors, which enables to
      estimate total atmospheric inputs of elements, was employed to study processes
      related to ionic flow through a tree canopy. The investigations were conducted
      within a beech forest in the Karkonosze Mountains, in 1996-1997. An analysis of
      net canopy exchange (throughfall flux-atmospheric input) revealed that NH4+, NO3
      , H+ had been retained in the canopy, Ca2+, Na+, Cl-, SO(2-)4, PO(3-)4 flowed
      passively, whereas K+ and Mg2- had been removed from the tree foliage. Ammonium
      absorption was more efficient than that of NO3- ions, because NH4+ was taken up
      from rain-waters and aerosol-gaseous fraction of the atmospheric input, whereas
      NO3- ions were captured primarily from the latter source. Retention of H+ was
      also related exclusively to the aerosol-gaseous input. Leaching losses of K+ and
      Mg2+ did not result from exchange reactions of these ions with retained H+, but
      from ionic exchange between NH4+ and K+ + Mg2+. At the same time, neutralisation
      of H+ in the canopy has been attributed to NO3- absorption, resulting most likely
      from HNO3 vapour penetration into the plants.

PMID- 11996386
TI  - The presence of a river bird, the dipper, in relation to water quality and biotic
      indices in central Italy.
AB  - A good water quality bio-indicator should be sensitive to different forms of
      water degradation in any geographical area, and effectively track water quality
      changes in time. We investigated whether the presence of a bird, the dipper
      (Cinclus cinclus), in 47 reaches of 35 streams of central Italy was affected by
      stream pollution as assessed by the Extended Biotic Index. Data from the
      literature and interviews with ornithologists furnished information about past
      dipper presence and water quality in the study streams. In 93.3% of cases dippers
      occurred in unpolluted reaches. The dipper was absent from 93.7% of polluted or
      strongly polluted streams. Dippers disappeared from 50% of the study streams for
      which past information was available. In a few streams dippers disappeared after
      the quality of water had degraded. Water quality degradation in the study area,
      especially in the hill streams, is causing dipper areale to contract to higher
      altitudes. Dipper is a good water quality bio-indicator for Mediterranean
      streams.

PMID- 11996387
TI  - Dating of marine sediments and time evolution of heavy metal concentrations in
      the Bay of Cadiz, Spain.
AB  - In this paper the time evolution of heavy metal concentration of Pb, Zn, Cd and
      Hg, in the sediments of the Bay of Cadiz (southwest of Spain) is studied during
      the past century, as a result of the industrial influence in the zone. The study
      has been performed using sedimentary profiles that have been extracted from the
      seabed. The measurement of 210Pb and 137Cs radionuclides has provided the dating
      of the sediment layers, up to a depth corresponding to the age of 115 years. The
      relative sedimentation rates obtained are around 0.2 cm/year. The 137Cs activity
      profile reflects the concentration of this radionuclide in the atmosphere and
      into aquatic systems during the second half of the twentieth century. This
      profile has been used to ratify the results provided by the 210Pb dating method.

PMID- 11996388
TI  - Speaking up on fundamental issues: a busy presidential year.

PMID- 11996389
TI  - What is your diagnosis? Eosinophilic folliculitis and furunculosis.

PMID- 11996390
TI  - Canine status epilepticus: a retrospective study of 50 cases.
AB  - The medical records of 50 dogs that exhibited generalised convulsive tonic-clonic
      (GCTC) status epilepticus (SE) were reviewed and compared with the records of 50
      dogs that exhibited non-SE GCTC seizures. The mean age, bodyweight and gender of
      the patients in both groups were not significantly different. Dogs in the non-SE
      group were two times more likely to be an idiopathic epileptic than to have
      secondary epileptic seizures. The SE group was more likely to have abnormalities
      on cerebrospinal fluid analysis, but not more likely to have abnormalities
      detected on computed tomography, when compared with the non-SE group. SE was 1.57
      times more likely if the cause for the seizures was secondary or reactive
      epilepsy rather than idiopathic or primary epilepsy. In conclusion, dogs that
      exhibit SE should be thoroughly investigated for secondary causes.

PMID- 11996391
TI  - Serological survey of leptospiral infection in kennelled dogs in Italy.
AB  - Two hundred and forty-five dogs were examined serologically for the presence of
      antibodies against different serovars of Leptospira interrogans. The dogs
      belonged to five different groups: group 1 was composed of clinically healthy pet
      dogs referred for a regular veterinary check-up visit or for vaccination; group 2
      was composed of stray dogs; and groups 3, 4 and 5 were composed of dogs
      maintained in three different kennels which had varying standards of hygiene.
      Seventy-two out of the 245 dogs examined were seropositive for leptospirosis. In
      group 1, there were 3-4 per cent seropositive dogs; in group 2, 30.3 per cent; in
      group 3, 13.8 per cent; in group 4, 38.6 per cent; and in group 5, 49.2 per cent.
      This study demonstrates that leptospiral infection is common in dogs housed in
      kennels, despite most of them being vaccinated, and that crowding of animals into
      unsanitary quarters is associated with a high prevalence of infection. The most
      common infecting serovars found were bratislava and grippotyphosa, confirming
      recent observations that demonstrate a significant change in the epidemiology of
      canine leptospirosis.

PMID- 11996392
TI  - Thoracolumbar disc disease in 71 paraplegic dogs: influence of rate of onset and
      duration of clinical signs on treatment results.
AB  - Seventy-one paraplegic dogs with confirmed intervertebral thoracolumbar disc
      disease and intact deep pain sensation were treated by hemilaminectomy and
      fenestration of at least two adjacent discs. The success rate of treatment in the
      overall population was 86 per cent (61/71 cases), with a mean length of time to
      regaining the ability to walk of 10.8 days and a mean follow-up time of 29
      months. The rate of onset of clinical signs significantly influenced the clinical
      outcome (P=0.01) but not the length of recovery time (P=0.45). Conversely, the
      duration of clinical signs did not seem to significantly affect the outcome
      (P=0.27), but did affect the length of recovery time (P=0.001). Animals which had
      shown clinical signs for more than six days took significantly longer to regain
      the ability to walk (ie, an additional 6.9 days, P=0.04 and 4.5 days, P=0.01),
      when compared with those which had shown clinical signs for less than two days,
      or more than two but less than six days, respectively.

PMID- 11996393
TI  - Use of proligestone in the management of three German shepherd dogs with
      pituitary dwarfism.
AB  - Three German shepherd dogs were diagnosed with pituitary dwarfism and
      subsequently treated with proligestone. Treatment resulted in development of an
      adult hair coat, increased bodyweight and elevated insulin-like growth factor-1
      concentration. Two dogs received thyroid supplementation during proligestone
      therapy. Adverse effects (cystic endometrial hyperplasia and acromegaly) were
      reported in two cases. No side effects were reported in the remaining case. This
      is the first report of the use of proligestone in the management of pituitary
      dwarfism.

PMID- 11996394
TI  - Neurological dysfunction in three dogs and one cat following attenuation of
      intrahepatic portosystemic shunts.
AB  - Neurological dysfunction is an uncommon complication following extrahepatic
      portosystemic shunt ligation. Three dogs and one cat are described that developed
      neurological signs within 21 to 42 hours of attenuation of intrahepatic
      portosystemic shunts. None of these cases had biochemical evidence of hepatic
      encephalopathy postoperatively. Two dogs died during management of status
      epilepticus following aspiration of food. One dog died six months
      postoperatively. The cat had persistent neurological dysfunction at discharge,
      but was alive and had recovered most of its neurological function at the time of
      writing, 37 months after surgery. This report demonstrates the potential for
      animals with intrahepatic portosystemic shunts to develop postoperative
      neurological signs and highlights the difficulty of managing such cases. Two dogs
      had both intrahepatic and extrahepatic portosystemic shunts. Large intestinal
      malrotation (partial situs inversus) may have been linked to the development of a
      portosystemic shunt in the remaining dog.

PMID- 11996395
TI  - Body cavity lipomas in six dogs.
AB  - Histologically confirmed lipomas were surgically removed from the thoracic or
      abdominal cavities of six dogs. Three dogs had a large intra-abdominal mass
      causing severe abdominal distension. Two dogs had a mass extending into the
      pelvic canal, compressing the colon and causing obstipation. One dog with an
      intrathoracic mass had a history of coughing and intermittent cyanosis. All dogs
      had complete resolution of signs after surgical resection of the tumour.
      Recurrence occurred in one dog with an abdominal lipoma, two years after the
      initial surgery. This recurrent lipoma was treated successfully by surgical
      resection.

PMID- 11996396
TI  - Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute
      renal failure in a dog.
AB  - Isoniazid-induced seizures resulted in rhabdomyolysis and associated acute renal
      tubular necrosis in a dog. Rhabdomyolysis and myoglobinuric renal failure,
      although recognised in the dog, are reported infrequently as a consequence of
      seizures. The clinical presentation of isoniazid toxicity in a dog is described.

PMID- 11996397
TI  - Violence towards animals and humans: exploring the link.

PMID- 11996398
TI  - Putting health and safety into practice.

PMID- 11996399
TI  - An update on respiratory syncytial virus epidemiology: a developed country
      perspective.
AB  - Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract
      infections in infants and young children worldwide, and an important cause of
      morbidity, hospitalization, and mortality. The infections caused by RSV are
      seasonal, peaking predictably in the winter months in temperate climates, and in
      the hottest months and the rainy season in tropical climates. The involvement of
      the lower respiratory tract, manifest clinically as bronchiolitis or pneumonia,
      is the hallmark of severe RSV disease. Other indicators of severe disease include
      requirement for, and duration of, hospitalization, supplemental oxygen,
      management in an intensive care setting, and mechanical ventilation. Host-related
      risk factors for severe RSV disease include preterm birth, infection before 6
      months of age, chronic lung disease, and congenital heart disease. Environmental
      risk factors for severe RSV infection include poverty, crowding, exposure to
      tobacco smoke, and malnutrition. Factors that increase frequency of the infection
      include young age, multiple gestation, family history of atopy, lack of parental
      education, household crowding, older school-age siblings, lack of breast feeding,
      day-care attendance, passive smoke exposure, and discharge from a neonatal
      intensive care unit between September and December. Recent studies in Europe,
      North America and Japan have evaluated the number of children affected as well as
      the medical resources necessary to care for these children. Continuing
      surveillance is the key to tracking the seasonality, risk factors, morbidity and
      mortality associated with RSV infection. Epidemiological studies are also the
      basis for development of appropriate local prevention strategies.

PMID- 11996400
TI  - Respiratory syncytial virus prophylaxis--the story so far.
AB  - Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that
      infects nearly all children by the age of 2 years. It is responsible for
      significant morbidity and mortality worldwide among certain high-risk paediatric
      populations. Therapy is sub-optimal for RSV, thus treatment focuses on
      ameliorating symptoms. Since discovery of the virus in the 1950s, efforts have
      been ongoing to develop a safe and effective vaccine. These efforts have met with
      serious obstacles. Passive immunoprophylaxis presents a viable alternative to
      active immunization. In 1998, the genetically engineered humanized monoclonal
      antibody (palivizumab) was granted FDA (Food and Drug Administration) approval
      for prophylaxis of high-risk children in the United States; EMEA (European Agency
      for the Evaluation of Medicinal Products) approval followed in 1999 for Europe.
      It is now approved in over 45 countries worldwide. Palivizumab was shown to
      significantly reduce RSV-related hospitalizations in North America and Europe
      with few adverse effects. Clinical trial and outcomes data documenting experience
      with palivizumab to date continue to extend the initial safety and efficacy
      observations.

PMID- 11996401
TI  - The association between respiratory syncytial virus infection and reactive airway
      disease.
AB  - Evidence has been accumulating that respiratory syncytial virus (RSV) lower
      respiratory tract infection (LRTI) in infants may be linked to subsequent
      development of reactive airway disease (RAD) in childhood, and therefore research
      into the prevention of RSV LRTI may have important implications for the
      prevention of RAD. This article reviews the epidemiological evidence linking
      RSVand RAD and some ofthe theories concerning cellular and molecular mechanisms
      of post-viral airway inflammation in order to understand how RSV prophylaxis may
      assist in reducing the occurrence of RSV LRTI and RAD.

PMID- 11996402
TI  - Development of a potent respiratory syncytial virus-specific monoclonal antibody
      for the prevention of serious lower respiratory tract disease in infants.

PMID- 11996403
TI  - Risk factors for severe respiratory syncytial virus infection in infants.
AB  - Severe respiratory syncytial virus (RSV) disease is associated with unacceptable
      morbidity and mortality in children, especially in young children. Underlying
      conditions including prematurity with or without bronchopulmonary dysplasia,
      congenital heart disease, immunosuppression or another underlying respiratory
      condition, such as cystic fibrosis, increase the risk of contracting and
      developing severe RSV disease. Environmental factors such as crowding, day-care
      attendance, and exposure to passive smoke can increase the risk of severe RSV
      disease. Children with severe RSV disease often require intensified medical care,
      including hospitalization, which places a burden on the child, the family, and
      the health care system. There are currently no effective curative treatments for
      severe RSV disease. Preventive measures, such as infection control and
      prophylaxis, appear to be the best options in the management of RSV disease in
      these high-risk patients.

PMID- 11996404
TI  - Basal levels of DNA strand breaks in human leukocytes determined by comet assay.
AB  - In order to determine background levels of DNA strand breaks, we examined 80
      healthy individuals by comet assay considering age, sex, and smoking as
      confounding factors. Only age was found to have a significant effect on basal
      levels. One thousand cells of each donor were graded by eye into 5 categories
      according to the amount of DNA in the tail: classification group A (no damage)
      <5%, B (low damage) 5-20%, C (medium damage) 20-40%, D (high damage) 40-95%, and
      group E (total damage) >95%. The interpretation of the comet assay was modified
      to achieve a tail factor, which represents the DNA damage of 1000 scored cells as
      a single number, without the need of an image analysis software package. Hydrogen
      peroxide and bleomycin used for in vitro exposure of lymphocytes, produced clear
      dose-related responses in the comet assay. Our data encourage the application of
      the used classification model for a sensitive and fast quantification of DNA
      damage. Results in this study are in agreement with most of the earlier
      investigations.

PMID- 11996405
TI  - Increased lead excretion in hypothyroid patients after levothyroxine medication.
AB  - In a recent publication we hypothesized that increased bone metabolism induced by
      thyroid hormones should increase lead excretion even in lead unexposed subjects.
      To examine this hypothesis, 10 hypothyroid patients were investigated before and
      after substitution therapy with levothyroxine. After a mean of 9 wk after onset
      of therapy (patients were then in an euthyroid state), lead concentrations in
      urine (PbU) corrected by the individual creatinine in urine were increased (p =
      .007), while lead concentrations in blood (PbB) were slightly decreased (3.44 +/-
      1.73 vs. 2.74 +/- 1.38, p = .008). Desoxypyridinoline cross-links (Pyr), a
      sensitive marker for bone degradation and excreted in urine, correlated with PbU
      (r = .64, p = .002) but not with PbB. Additionally PbU significantly correlated
      with serum concentrations of free circulating T3 (fT3) or free circulating T4
      (fT4). Thus, we may suspect that increased lead excretion was induced by
      accelerated bone metabolism, since Pyr was increased after therapy (3.21 +/- 1.19
      vs. 6. 10 +/- 1.81 nM/mM Cr, p < .001), too.

PMID- 11996406
TI  - Urinary 8-hydroxydeoxyguanosine and sister chromatid exchanges in patients with
      total hip replacements.
AB  - Ion release from metal implants has been suspected to increase the risk of
      genotoxic effects in patients wearing orthopedic metal devices. In this study we
      used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage
      and the frequency of sister chromatid exchanges in lymphocytes to test a possible
      relationship between the concentrations of chromium or cobalt and the induction
      of cytogenetic modifications in 46 patients with total hip replacements. A broad
      range of individual levels of metals has been observed in these patients:
      chromium in blood, 1.59-14.11 microg/L; chromium in urine, 0.79-93.80 microg/24
      h; cobalt in blood, 0.77-37.80 microg/L; cobalt in urine, 2.59-166.94 microg/24
      h. By linear regression analysis, no significant correlation between urinary
      8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was
      found. However, cobalt in blood as well as 8-OHdG in urine were higher in
      patients with implants 3-4 yr old as compared to patients with implants 1-2 yr
      old. Smoking significantly increased the frequency of SCE. Our data do not
      indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or
      cobalt in patients with total hip replacements.

PMID- 11996407
TI  - Induction of 8-hydroxy-2'-deoxyguanosine by cobalt(II) and hydrogen peroxide in
      vitro.
AB  - In order to test the effects of cobalt on oxidative DNA damage, we measured the
      formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the presence of cobalt in
      calf thymus DNA and in DNA of human diploid fibroblasts. Treatment of calf thymus
      DNA with Co(II) at 500 microM hydrogen peroxide resulted in a dose-dependent
      increase in 8-OHdG, which culminated at 25 microM Co(II) (62.6 modified/10(5) dG)
      and declined at higher Co(II) concentrations [9.6 modified/10(5) dG at 250 microM
      Co(II)]. Incubation of calf thymus DNA with Co(II) alone did not cause an
      increase in 8-OHdG. Treatment of calf thymus DNA with H2O2, (0.25-2 mM) caused
      only a slight generation of 8-OHdG (2.7/10(5) dG, at 2 mM H2O2). Exposure of
      human diploid fibroblasts to Co(II) at 5-250 microM did not result in an increase
      in 8-OHdG in a dose-dependent manner, although treated cells showed significantly
      higher 8-OHdG levels than untreated controls (2.026 +/- 0.695 vs. 1.395 +/- 0.433
      8-OHdG/10(5) dG) at all concentrations. Our data indicate that in the presence of
      H2O2, Co(II) stimulates the in vitro formation of 8-OHdG.

PMID- 11996408
TI  - Neurobehavioral effects of vanadium.
AB  - It was our aim to study whether chronic exposure to vanadium reduces cognitive
      abilities. We investigated effects on attention, visuospatial and visuomotor
      functioning, reaction time, short-term memory, and prefrontal functioning. Forty
      nine vanadium exposed subjects with a mean vanadium level in urine (VanU) of 14.4
      micro/L and 49 controls (VanU: 0.8 microg/L) with the same socioeconomic
      background were investigated. Neuropsychological tests were done using a modified
      Wisconsin Card Sorting Test (WCST), Block Design Test (BDT), Visual Recognition
      Test (VRT), Simple Reaction Time (SRT), Choice Reaction (CR), Digit Symbol
      Substitution (DSS), and Digit Span (DS). Exposure was assessed by using the
      vanadium level in urine and serum. While there were significant differences in
      BDT and DSS, no differences were found in WCST, SRT, CR, and DS. Significant
      correlations existed between the vanadium levels in urine and serum and the
      cognitive deficits. Vanadium concentrations around 14.2 microg/L in urine reduce
      neurobehavioral abilities, particularly visuospatial abilities and attention.

PMID- 11996409
TI  - Furosemide and spironolactone reduce transmigration of leukocytes through
      endothelial cell monolayers.
AB  - Furosemide and spironolactone reduce transmigration of leukocytes through
      endothelial cell monolayers. Leukocytes play a tremendous role during
      inflammation. Leukocytes migrate from intravascular space into the tissue to
      attack microorganisms. Various agents are able to influence leukocyte
      recruitment. The influence of diuretics, such as furosemide and spironolactone,
      on inflammatory processes is not well known. The aim of our study was to examine
      the influence of furosemide and spironolactone on leukocyte migration through
      endothelial cell monolayers (ECM). Human umbilical vein endothelial cells were
      cultured on microporous membranes achieving a monolayer. Polymorphonuclear
      leukocytes (PMNL) were used in a currently described migration assay. PMNL and/or
      ECM were pretreated with furosemide and spironolactone using therapeutic, as well
      as higher and lower, concentrations. Furosemide (76 +/- 7.2%) and spironolactone
      (70 +/- 7.7%) were able to inhibit PMNL migration through ECM significantly, when
      both cell types were treated simulating the situation after an iv injection.
      Furosemide and spironolactone were identified as potent inhibitors of leukocyte
      migration through ECM.

PMID- 11996410
TI  - The clinical importance of defining family.

PMID- 11996411
TI  - Treatment of streptococcal pharyngitis.

PMID- 11996412
TI  - Treatment of Hansen's disease.

PMID- 11996413
TI  - Do NSAIDs help in acute or chronic low back pain?

PMID- 11996414
TI  - Management of Helicobacter pylori infection.
AB  - Helicobacter pylori is the cause of most peptic ulcer disease and a primary risk
      factor for gastric cancer. Eradication of the organism results in ulcer healing
      and reduces the risk of ulcer recurrence and complications. Testing and treatment
      have no clear value in patients with documented nonulcer dyspepsia; however, a
      test-and-treat strategy is recommended but for patients with undifferentiated
      dyspepsia who have not undergone endoscopy. In the office setting, initial
      serology testing is practical and affordable, with endoscopy reserved for use in
      patients with alarm symptoms for ulcer complications or cancer, or those who do
      not respond to treatment. Treatment involves 10- to 14-day multidrug regimens
      including antibiotics and acid suppressants, combined with education about
      avoidance of other ulcer-causing factors and the need for close follow-up. Follow
      up testing (i.e., urea breath or stool antigen test) is recommended for patients
      who do not respond to therapy or those with a history of ulcer complications or
      cancer.

PMID- 11996415
TI  - Information from your family doctor. What should I know about Helicobacter pylori
      infections?

PMID- 11996416
TI  - Spinal epidural abscess: a diagnostic challenge.
AB  - Epidural abscess of the spinal column is a rare condition that can be fatal if
      left untreated. Risk factors for epidural abscess include immunocompromised
      states such as diabetes mellitus, alcoholism, cancer, and acquired
      immunodeficiency syndrome, as well as spinal procedures including epidural
      anesthesia and spinal surgery. The signs and symptoms of epidural abscess are
      nonspecific and can range from low back pain to sepsis. The treatment of choice
      in most patients is surgical decompression followed by four to six weeks of
      antibiotic therapy. Nonsurgical treatment may be appropriate in selected
      patients. The most common causative organism in spinal epidural abscess is
      Staphylococcus aureus. Spinal epidural abscess involving actinomycosis is rare.

PMID- 11996417
TI  - Interviewing when family members are present.
AB  - The presence of family members at an office visit creates unique opportunities
      and challenges for the physician while interviewing the patient. The physician
      must address issues of confidentiality, privacy, and agency. Special skills are
      required to respectfully and efficiently involve family members, while keeping
      the patient at the center of the visit. A core set of interviewing skills exists
      for office visit interviews with family members present. These skills include
      building rapport with each participant by identifying their individual issues and
      perspectives, and encouraging participation by listening to and addressing the
      concerns of all persons. Physicians should also avoid triangulation, maintain
      confidentiality, and verify agreement with the plan. It may be necessary to use
      more advanced family interviewing skills, including providing direction despite
      problematic communications; managing conflict; negotiating common ground; and
      referring members to family therapy.

PMID- 11996418
TI  - Radiologic bone assessment in the evaluation of osteoporosis.
AB  - Osteoporosis affects nearly 28 million elderly Americans. Its major clinical
      manifestation is fragility fractures of the spine, hip, and distal radius. Low
      bone mass is the most important risk factor for a fragility fracture. In 1994,
      the World Health Organization defined osteoporosis on the basis of a bone mineral
      density that is 2.5 standard deviations below that in peak young normal persons.
      Three common imaging modalities used to assess bone strength are dual-energy x
      ray absorptiometry, quantitative computed tomography, and calcaneal
      ultrasonography. The first two modalities measure bone mineral density in both
      the lumbar spine and peripheral sites. It is thought that calcaneal
      ultrasonography measures bone architecture and density. Unlike the other studies,
      ultrasonography currently cannot be used for monitoring skeletal changes over
      time or evaluating response to therapy.

PMID- 11996419
TI  - Venomous snakebites in the United States: management review and update.
AB  - Venomous snakebites, although uncommon, are a potentially deadly emergency in the
      United States. Rattlesnakes cause most snakebites and related fatalities.
      Venomous snakes in the United States can be classified as having hemotoxic or
      neurotoxic venom. Patients with venomous snakebites present with signs and
      symptoms ranging from fang marks, with or without local pain and swelling, to
      life-threatening coagulopathy, renal failure, and shock. First-aid techniques
      such as arterial tourniquets, application of ice, and wound incisions are
      ineffective and can be harmful; however, suction with a venom extractor within
      the first five minutes after the bite may be useful. Conservative measures, such
      as immobilization and lymphatic constriction bands, are now advocated until
      emergency care can be administered. Patients with snakebites should undergo a
      comprehensive work-up to look for possible hematologic, neurologic, renal, and
      cardiovascular abnormalities. Equine-derived antivenin is considered the standard
      of care; however, a promising new treatment is sheep-derived antigen binding
      fragment ovine (CroFab), which is much less allergenic. Although there is no
      universal grading system for snakebites, a I through IV grading scale is
      clinically useful as a guide to antivenin administration. Surgical intervention
      with fasciotomy is now reserved for rare cases. Snakebite prevention should be
      taught to patients.

PMID- 11996420
TI  - Information from your family doctor. Snakebite prevention and first aid.

PMID- 11996421
TI  - Assessing oral malignancies.
AB  - Oral cancers account for approximately 3 percent of all cases of cancer in the
      United States. An estimated 30,000 people will be diagnosed with oral cancer this
      year, and about one half of them will eventually die of the disease. The most
      common type of oral cancer is squamous cell carcinoma. Sixty percent of oral
      cancers are well advanced by the time they are detected, even though physicians
      and dentists frequently examine the oral cavity. The two most important risk
      factors for oral cancer are tobacco use and heavy alcohol consumption. The keys
      to reducing mortality are prevention and control. The earlier any intraoral or
      extraoral abnormalities or lesions are detected and biopsied, the more lives can
      be saved. Controversy exists whether screening programs effectively reduce the
      mortality rate. Specific step-by-step guidelines should be followed to perform an
      adequate examination of the head and neck.

PMID- 11996422
TI  - Information from your family doctor. Protecting oral health during cancer
      therapy.

PMID- 11996423
TI  - Infant botulism.
AB  - Although the worldwide incidence of infant botulism is rare, the majority of
      cases are diagnosed in the United States. An infant can acquire botulism by
      ingesting Clostridium botulinum spores, which are found in soil or honey
      products. The spores germinate into bacteria that colonize the bowel and
      synthesize toxin. As the toxin is absorbed, it irreversibly binds to
      acetylcholine receptors on motor nerve terminals at neuromuscular junctions. The
      infant with botulism becomes progressively weak, hypotonic and hyporeflexic,
      showing bulbar and spinal nerve abnormalities. Presenting symptoms include
      constipation, lethargy, a weak cry, poor feeding and dehydration. A high index of
      suspicion is important for the diagnosis and prompt treatment of infant botulism,
      because this disease can quickly progress to respiratory failure. Diagnosis is
      confirmed by isolating the organism or toxin in the stool and finding a classic
      electromyogram pattern. Treatment consists of nutritional and respiratory support
      until new motor endplates are regenerated, which results in spontaneous recovery.
      Neurologic sequelae are seldom seen. Some children require outpatient tube
      feeding and may have persistent hypotonia.

PMID- 11996424
TI  - Depressive disorders.

PMID- 11996425
TI  - Screening for skin cancer.

PMID- 11996426
TI  - Minimal excision technique for epidermoid (sebaceous) cysts.
AB  - Epidermoid cysts are asymptomatic, dome-shaped lesions that often arise from a
      ruptured pilosebaceous follicle. The minimal excision technique for epidermoid
      cyst removal is less invasive than complete surgical excision and does not
      require suture closure. The procedure is easy to learn, and most physicians
      experienced in skin surgery can perform the procedure after three to five
      precepted sessions. It involves making a 2- to 3-mm incision, expressing the cyst
      contents through compression and extracting the cyst wall through the incision.
      Gauze or a splatter shield should be used to protect the physician from spraying
      of cyst contents. The rarity of associated cancer makes histologic evaluation
      necessary only if unusual findings or clinical suspicion of cancer is present.
      Inflamed cysts are difficult to excise, and it is often preferable to postpone
      excision until inflammation has subsided.

PMID- 11996427
TI  - Information from your family doctor. Minimal excision technique for removal of an
      epidermoid cyst.

PMID- 11996428
TI  - Introduction to AAFP Summary of Recommendations for Periodic Health Examinations.
      American Academy of Family Physicians.

PMID- 11996429
TI  - Counseling, testing, and referral for HIV.

PMID- 11996430
TI  - How can I help my patient stop drinking?

PMID- 11996431
TI  - Sarcoidosis: a needle in the haystack.

PMID- 11996432
TI  - Arthritis in sarcoidosis.
AB  - AIMS AND METHODS: Sarcoidosis is systemic granulomatous disorder. Articular
      manifestations have received little attention in the literature. Case records of
      patients with sarcoidosis, presenting with articular symptoms between 1990-1999,
      were retrospectively analysed. RESULTS: Twenty nine patients, 15 males and 14
      females, median age 44 years (range 15-67 years) and median duration of articular
      symptoms of eight months diagnosed clinically (n=9) and on biopsy (n=20) were
      studied. Twenty five patients had arthritis as the presenting manifestation.
      Fifteen patients had chronic arthritis (> six months). Lofgren's syndrome was
      seen in 7% of the patients. Acute arthritis was episodic (n=4), more common in
      males (M:F = 9:5), predominantly affected lower limb joints and mimicked reactive
      arthritis. Chronic arthritis was more frequently observed in females (M:F = 1:2)
      and presented with involvement of bilateral symmetric hand joints, mimicking
      rheumatoid arthritis. Extra-articular manifestations like neuropathy and
      constitutional symptoms were observed in acute arthritis. Skin plaque,
      splenomegaly and interstitial lung disease were seen with chronic arthritis. At a
      median follow up of 12 months, 10/14 and 5/15 achieved complete remission whereas
      2/14 and 9/15 achieved partial remission of the articular symptoms in the acute
      and chronic groups, respectively. CONCLUSION: Arthritis in sarcoidosis is an
      early manifestation of disease and may mimic reactive or rheumatoid arthritis.
      Unsatisfactory response in chronic arthritis highlights the need for
      immunosuppressive drugs in addition to steroids.

PMID- 11996433
TI  - Prevalence of coronary risk factors among Indian physicians.
AB  - BACKGROUND AND OBJECTIVES: Prevalence of coronary risk factors has not been well
      studied in Indian physicians, therefore, to determine prevalence of selected
      lifestyle and biochemical coronary risk factors we performed this study. METHODS:
      Physicians attending a national conference were invited to participate. Of the
      1000 questionnaires circulated 256 physicians (221 males, 35 females) responded
      and were examined for presence of smoking, obesity, truncal obesity, hypertension
      and ECG abnormalities. Two hundred and thirty four physicians (91.4%, 203 males,
      31 females) underwent a fasting blood examination for determination of glucose
      and lipid profile. Subjects were divided into three age groups: Group I aged < 40
      years; Group II 40-49 years; and Group III > or = 50 years. RESULTS: Mean age of
      the study population was 41.7 +/- 9.3 years (range 26-70). There was no
      significant difference in the distribution of height, weight, body-mass index
      (BMI), waist and hip circumference and waist-hip ratio (WHR) in different age
      groups. Systolic blood pressure (BP) and fasting glucose and triglyceride levels
      increased with age in both males and females, while diastolic BP, total - LDL and
      HDL cholesterol levels did not change. Smoking or tobacco use was seen in five
      males (2.3%). Prevalence of obesity (BMI > or = 25.0 kg/m2) was in 104 (48.6%)
      males and 18 (51.4%) females. Truncal obesity diagnosed by WHR > 0.9 in males and
      > 0.8 in females was in 160 (72.4%) males and 23 (65.7%) females and a large
      waist circumference, > or = 100 cm in males and > or = 90 cm in females, was in
      58 (26.2%) males and 7 (20.0%) females. Hypertension (> or = 140/90) was in 74
      (33.5%) males and 7 (20%) females. A high prevalence of diabetes diagnosed using
      fasting blood glucose > or = 126 mg/dl or previous history was noted in males 19
      (9.4%), females 4 (12.9%). Prevalence of high total cholesterol levels > or = 200
      mg/dl was in 91 (44.8%) males and 10 (32.3%) females. High LDL cholesterol level
      (> or = 100 mg/dl) was in 144 (70.9%) males and 22 (70.9%) females and LDL levels
      > or = 130 mg/dl in 70 (34.5%) males and 9 (29.0%) female physicians. High
      triglyceride levels (> or = 200 mg/dl) were in 38 (18.7%) males and 4 (12.9%)
      females. Electrocardiographic abnormalities were present in seven subjects: Q
      waves in two males and one female and ST-T changes in three males and one female.
      BMI correlated significantly (p < 0.05) with systolic BP, fasting glucose, and
      triglycerides and WHR with systolic BP, diastolic BP, fasting glucose,
      cholesterol and triglyceride levels. CONCLUSIONS: There is a high prevalence of
      obesity, truncal obesity, hypertension and hypercholesterolaemia in Indian
      physicians while smoking, low HDL cholesterol and hypertriglyceridemia is low.
      The overall coronary risk is lower among Indian physicians as compared to
      previous Indian population studies.

PMID- 11996434
TI  - Multicentric clinical trials for safety and efficacy evaluation of alpha;beta
      arteether in complicated P. falciparum malaria.
AB  - OBJECTIVE: To evaluate efficacy of alpha;beta arteether in patients of P.
      falciparum malaria presenting with complications was undertaken in a multicentric
      clinical trial. METHOD: Each patient who consented to undergo clinical trial with
      parenteral Arteether was treated with a fixed dose schedule of Arteether given
      intramuscularly in a dose of 150 mg once a day on three consecutive days. Every
      patient was followed upto 28 days with clinical, haematological and
      parasitological monitoring every day upto one week and thereafter at 14, 21 and
      28 days. The response was assessed in terms of fever clearance time, parasite
      clearance time, cure rate and parasite reappearance rate. RESULTS: A total of 211
      patients of P. falciparum malaria were included in the study from four centres
      (Bhilai, Guwahati, Jamshedpur and Rourkela). Results of this study showed that
      fever clearance time ranged between 24-168 hours, parasite clearance time ranged
      between 24-120 hours and overall mortality ranged between 4-8.5%. Out of 211,
      only 14 patients expired during the study, of these, 10 patients expired within
      first two days i.e. before completing the three day schedule of arteether
      therapy. Tolerability to arteether injection was good in all these patients and
      no untoward effects were experienced or reported during the study. Overall cure
      rate observed in these studies was 93%. CONCLUSION: This study shows a rapid
      parasite and fever clearance in patients of complicated P. falciparum malaria.

PMID- 11996435
TI  - Asymptomatic malarial parasitaemia in Tamil Nadu.
AB  - AIM: The aim of the study was to determine the community prevalence of
      asymptomatic malarial parasitaemia in the state of Tamil Nadu. METHODS: Free
      medical camps were organised in three randomly selected districts of Tamil Nadu,
      namely Dindigul, Ramnad and Thanjavur districts in November, 1997. Proportionate
      to population size cluster survey method was followed to collect peripheral blood
      smear by finger prick from 30 clusters in each district. Fifteen households were
      randomly selected from each district with the target age group of 15-45 years.
      Peripheral blood smears were stained by Leishman's stain and the slides were
      examined end to end by two independent experts to diagnose malarial parasites.
      RESULTS: The male:female ratio of the population studied was 1:1.6. Asymptomatic
      malaria was identified in 17 out of 569 individuals screened with a positive rate
      of 2.9% (CI 1.5-4.3). Out of the 17 malarial positive peripheral smears 15 were
      P. vivax and only two were P. falciparum with the predominance of gametocyte
      stage. CONCLUSION: This study reaffirms the prevalence of asymptomatic malaria in
      Tamil Nadu especially with P. vivax.

PMID- 11996436
TI  - Changes in the isoprenoid pathway in syndrome X.
AB  - This study assessed the changes in digoxin and some other metabolites of the
      isoprenoid pathway in metabolic syndrome X presenting with multiple lacunar
      state. There was an increase in plasma HMG CoA reductase activity with a
      consequent increase in serum digoxin, which caused a reduction in RBC membrane
      Na+-K+ ATPase activity. There was an increase in serum tryptophan and its
      metabolites and a decrease in tyrosine and its metabolites. Serum magnesium was
      decreased with consequent alteration in the metabolism of glycosaminoglycans and
      glycolipids. Increase in dolichol, another product of the isoprenoid pathway
      resulted in alteration in glycoprotein metabolism. Changes in the composition of
      membrane glycosaminoglycans, glycoproteins and cholesterol:phospholipid ratio
      were also observed in this disorder leading to decreased lysosomal stability.
      Decrease in ubiquinone, another isoprenoid metabolite resulted in alteration in
      the free radical generation. Membrane Na+-K+ ATPase inhibition due to digoxin,
      altered membrane structure, increased tryptophan catabolites and decreased
      tyrosine catabolites can lead on to increased intracellular calcium and reduced
      intracellular magnesium which can account for the symptoms of syndrome X.

PMID- 11996437
TI  - Current concepts in the management of osteoarthritis.

PMID- 11996438
TI  - Adverse effects of hormone replacement therapy.

PMID- 11996439
TI  - Postal Stamp of Edward Jenner (1749-1823).

PMID- 11996440
TI  - Pictorial CME. SVC syndrome is a rare complication if retrosternal MNG.

PMID- 11996441
TI  - Diabetic nephropathy in type 2 diabetes: the Indian experience.

PMID- 11996442
TI  - Lipid profile in rheumatoid arthritis and its relation to disease activity.
AB  - AIM OF THE STUDY: To ascertain whether--1. Serum lipids are altered in rheumatoid
      arthritis (RA) patients and 2. Disease activity has any role in altering lipid
      profile. METHODOLOGY: Lipid profiles of 25 RA cases were compared with age and
      sex matched controls. RESULTS: Serum triglycerides (STG) and total cholesterol
      (TC) were found to be significantly lower in RA patients. In patients with very
      active disease, activity index (AI) > 80, STG, TC and low-density lipoprotein
      (LDL-C) were significantly lower as compared to controls. For TG 'r' value of 
      0.483 indicated negative correlation between disease activity and TG values,
      though the correlation is not significant (p > 0.05). For TC 'r' value (-0.0551)
      indicates negative correlation between disease activity and serum TC.

PMID- 11996443
TI  - Blackwater fever treated with artemether.
AB  - Blackwater fever is a rare manifestation of falciparum malaria characterized by
      sudden intravascular hemolysis followed by fever and hemoglobinuria. We present a
      case of blackwater fever, having occurred after administration of quinine, which
      was treated successfully with artemether.

PMID- 11996444
TI  - Reversal of catecholamine induced cardiomyopathy in a patient with bilateral
      malignant pheochromocytoma.
AB  - A patient of catecholamine induced cardiomyopathy (CMP) due to bilateral
      malignant adrenal pheochromocytoma (PCC), successfully reversed on treatment is
      described here. To the best of our knowledge, this is first report of
      catecholamine induced CMP due to bilateral malignant adrenal PCC, which could be
      reversed after surgery.

PMID- 11996445
TI  - Dual kidney transplantation--a solution for less than ideal brain dead donors.
AB  - For renal transplantation, an elderly cadaver donor is often rejected because of
      the relatively poor long-term graft survival. Considering that a number of
      potential recipients are waiting for a renal transplant, dual kidney
      transplantation would be a more appropriate approach in this situation. We report
      one such case with a successful outcome.

PMID- 11996446
TI  - A fatal case of systemic brucellosis.
AB  - A 65 years man presented with fever, drenching sweats, progressive dyspnoea,
      backache and weight loss. On examination, he had wide pulse pressure, clubbing,
      retinal hemorrhages, aortic and mitral regurgitation, hepatosplenomegaly, lower
      spinal tenderness and bilateral basal crepitations. Transthoracic 2D
      echocardiography showed a large vegetation on the aortic valve. Antibody titers
      for brucella were positive. X-ray spine was suggestive of brucella spondylitis.
      Early surgical intervention was planned and the patient was given combination
      antibiotic therapy. The course was complicated by renal failure and the patient
      succumbed while being taken up for surgery.

PMID- 11996447
TI  - Localized hypertrophy of hand in syringomyelia.
AB  - Segmental amyotrophy is a common feature resulting from extension of the syrinx
      into the anterior horns. Segmental hypertrophy in the form of
      chiromegaly/podomegaly or limb and hemi-hypertrophy are rare but well recognized
      clinical feature of syringomyelia. We report a case of hand hypertrophy secondary
      to syringomyelia. Hypertrophy of the hands is a rare but interesting feature of
      syringomyelia and in all cases of enlargements of hands syringomyelia should be
      considered in the differential diagnosis.

PMID- 11996448
TI  - Cortical blindness: an unusual presentation of eclampsia.

PMID- 11996449
TI  - Orbital varix.

PMID- 11996450
TI  - Malignant pleural mesothelioma.

PMID- 11996451
TI  - Bronchial epithelial-myoepithelial carcinoma.

PMID- 11996452
TI  - Eosinophilic fasciitis.

PMID- 11996453
TI  - Acute lymphoblastic leukemia presenting as breast mass.

PMID- 11996454
TI  - Prazosin therapy and scorpion envenomation.

PMID- 11996455
TI  - Lactulose in the prevention of recurrent urinary tract infection.

PMID- 11996456
TI  - Tumoral calcinosis with renal calculus.

PMID- 11996457
TI  - Superstition and fatal diabetic foot.

PMID- 11996458
TI  - Intrarenal extension of pancreatic pseudocysts.

PMID- 11996459
TI  - Painful inguinal mass: a rare presentation of complete androgen resistance.

PMID- 11996460
TI  - Stem cells: more about the 'monster of Loch Ness'.

PMID- 11996461
TI  - Is pharmacokinetically guided chemotherapy dosage a better way forward?

PMID- 11996462
TI  - FDG-PET for response assessment: answers in search of questions.

PMID- 11996463
TI  - The insulin-like growth factor system as a therapeutic target in colorectal
      cancer.
AB  - The purpose of this review is to examine recent evidence that investigates the
      role of the insulin-like growth factor (IGF) system in colorectal cancer. We
      concentrate on the evidence that makes the case for the investigation of
      strategies that might be used to disrupt the IGF system in prevention and
      treatment. Even though the weight of evidence suggests that components of the IGF
      system may be appropriate targets, there are a lack of studies that make a
      systematic characterisation of all the system components in human colorectal
      cancer. It is anticipated that this information, and the new therapeutic
      molecules which follow, will impact on the prevention and treatment of patients
      with this disease.

PMID- 11996464
TI  - FDG-PET imaging in the management of non-small-cell lung cancer.
AB  - Lung cancer is currently the leading cause of cancer-related death in both men
      and women in most Western countries. Tumour stage is the strongest prognostic
      factor and the most important parameter guiding treatment decision making.
      Metabolic positron emission tomography imaging with fluorodeoxyglucose (FDG-PET)
      has consistently proved superior to conventional imaging for staging of non-small
      cell lung cancer and provides information of greater prognostic significance than
      can be obtained using conventional approaches. FDG-PET has been approved in the
      USA, Germany and the UK as a basic and invaluable tool in the management of lung
      cancer.

PMID- 11996465
TI  - Positron emission tomography for assessment of the response to induction
      radiochemotherapy in locally advanced oesophageal cancer.
AB  - AIMS: This prospective study was designed to determine the utility of 18F
      labelled deoxyglucose (FDG) in positron emission tomography (PET) (FDG-PET) for
      assessing the response to neoadjuvant chemoradiation therapy (CRT) in locally
      advanced oesophageal tumours. PATIENTS AND METHODS: Thirty-six patients with
      locally advanced oesophageal cancer (clinical T4 stage) without organ metastases,
      underwent FDG-PET before and 1 month after CRT. Patients were classified as major
      responders by serial FDG-PET when the post-CRT PET demonstrated a strong
      reduction of FDG uptake at the primary tumour site (>80% reduction of tumour-to
      liver uptake ratio) without any abnormal FDG uptake elsewhere in the body. PET
      response was compared with histology obtained during post-induction transthoracic
      oesophagectomy. RESULTS: A strong correlation was found between the extent of
      lymph node (LN) involvement as shown by the pre-CRT PET and the major response
      rate (P = 0.001): such response occurred in nine of 11 N0M0 patients (82%), in
      three of nine N(1-2)M0 patients (33%) and in two of 16 patients (13%) with
      distant lymphatic spread. Such a correlation was not found for computed
      tomography or endoscopic ultrasonography. The sensitivity of serial FDG-PET for a
      major CRT response was 10 of 14 (71%), its specificity 18 of 22 (82%). The
      concordance between the response assessment by PET and histopathology was 78%.
      The median survival time after CRT of PET major responders compared with PET non
      major responders was 16.3 months and 6.4 months, respectively. The metabolic
      response as measured by serial FDG-PET is a stronger prognostic factor for
      overall survival (P = 0.002) than the extent of LN involvement seen on the
      pretreatment FDG-PET (P = 0.087). CONCLUSIONS: These data indicate that CRT
      response as assessed by serial FDG-PET is strongly correlated with pathological
      response and survival.

PMID- 11996466
TI  - Macronutrients and colorectal cancer: a Swiss case-control study.
AB  - BACKGROUND: A role of energy and various nutrients, including protein, sugar,
      saturated and unsaturated fats, in colorectal cancer risk has been suggested, but
      should be better defined. PATIENTS AND METHODS: The association between dietary
      intake of various macronutrients and colorectal cancer risk was analysed using
      data from a case-control study conducted between 1992 and 2000 in the Swiss
      Canton of Vaud. The study comprised 286 case subjects (174 males, 112 females;
      median age 65 years) with incident, histologically confirmed colon (n = 149) or
      rectal (n = 137) cancer, and 550 control subjects (269 males, 281 females; median
      age 59 years) admitted to the same University Hospital for a wide spectrum of
      acute non-neoplastic conditions. Dietary habits were investigated using a
      validated food frequency questionnaire, including questions on 79 foods or
      recipes and on individual fat intake pattern. Multivariate odds ratios (OR) were
      obtained after allowance for age, sex, education, physical activity and energy
      intake. RESULTS: The risk of colon and rectal cancer increased with total energy
      intake (OR in highest and lowest tertile, 2.0 and 2.2, respectively). There was
      no significant relation with starches or proteins, a significant inverse relation
      with sugars (OR for the highest tertile, 0.5), a direct trend in risk of
      borderline significance for saturated fats (OR = 1.4 for the highest tertile),
      and significant inverse trends for monounsaturated (OR = 0.6) and polyunsaturated
      fats (OR = 0.6). CONCLUSIONS: These findings confirm that energy intake is
      directly related to colorectal cancer risk, and that different types of fat may
      have different roles in colorectal carcinogenesis.

PMID- 11996467
TI  - Relationship between exposure and toxicity in high-dose chemotherapy with
      cyclophosphamide, thiotepa and carboplatin.
AB  - BACKGROUND: High-dose chemotherapy in combination with peripheral blood
      progenitor cell transplantation is widely used in the treatment of several
      malignancies. The use of high-dose chemotherapy can be complicated by the
      occurrence of severe and sometimes life threatening toxicity. A wide interpatient
      variability in toxicity is encountered, which may be caused by variability in the
      pharmacokinetics of the agents. The aim of this study was to establish the
      pharmacokinetics of cyclophosphamide, thiotepa, carboplatin and all relevant
      metabolites in a widely used high-dose combination and to study possible
      relationships between the pharmacokinetics and toxicity. PATIENTS AND METHODS:
      Blood samples were collected from patients treated with modifications of the CTCb
      regimen consisting of cyclophosphamide (1000-1500 mg/m2/day), carboplatin (265
      400 mg/m2/day) and thiotepa (80-120 mg/m2/day) as short infusions for four
      consecutive days. Thiotepa and its main metabolite tepa, ultrafilterable
      carboplatin, cyclophosphamide and its activated metabolites 4
      hydroxycyclophosphamide and phosphoramide mustard were determined.
      Pharmacokinetics were assessed with the use of population pharmacokinetic
      analyses. Relationship between the area under the concentration-time curves
      (AUCs) of these compounds and toxicity were tested. RESULTS: A total of 46
      patients (83 courses of chemotherapy) was included. Relationships were identified
      between elevation of transaminases and the thiotepa and tepa AUC, mucositis and
      the tepa AUC and ototoxicity and the carboplatin AUC. A strong trend between the
      4-hydroxycyclophosphamide AUC and veno-occlusive disease was found. CONCLUSIONS:
      The complex pharmacokinetics of the different agents and their metabolites have
      been established and several relationships between the pharmacokinetics and
      toxicity were identified. These findings may form the basis for further treatment
      optimisation and dose-individualisation in this high-dose chemotherapy
      combination.

PMID- 11996468
TI  - Phase I study of MEN-10755, a new anthracycline in patients with solid tumours: a
      report from the European Organization for Research and Treatment of Cancer, Early
      Clinical Studies Group.
AB  - A phase I study was performed with MEN-10755, a novel anthracycline with
      promising preclinical antitumour activity, in patients with solid tumours to
      determine the maximum tolerated dose (MTD); the dose-limiting toxicities (DLTs);
      to document antitumour activity; and to propose a safe dose for phase II
      evaluation. MEN-10755 at a starting dose of 15 mg/m2/week was given by short
      intravenous infusion weekly for 3 weeks and cycles were repeated every 28 days.
      Twenty-four patients received 55 cycles. Doses of MEN-10755 were 15, 30, 40 and
      45 mg/m2. At a dose of MEN-10755 45 mg/m2, treatment could not be given as
      planned due to neutropenia and one patient developed a decrease in cardiac
      function. This dose level was considered to be the MTD. Chemotherapy-naive
      patients could be treated with 40 mg/m2/week, and only one DLT (grade 4
      neutropenia) was observed. At that dose, three of six chemotherapy pretreated
      patients developed a DLT during their first treatment cycle: one patient
      developed a grade 4 thrombocytopenia, one patient a grade 4 neutropenia and one
      patient developed a grade 3 acute hypersensitivity reaction resulting in
      discontinuation of treatment. At this dose level, one other patient did not
      receive treatment on day 15 as planned due to grade 3 neutropenia. No responses
      were observed. MEN-107555 at a dose of 30 mg/m2/week in pretreated patients and
      40 mg/m2/week in chemotherapy-naive patients for three consecutive weeks followed
      by 1 week rest is recommended for phase II testing.

PMID- 11996469
TI  - Preclinical and phase I study of oxaliplatin and topotecan in combination in
      human cancer.
AB  - BACKGROUND: DNA damage caused by platinum agents is frequently followed by
      induction of topoisomerase I, providing a rationale for use of platinum-based
      compounds with topoisomerase I inhibitors. MATERIALS AND METHODS: We studied the
      effect of a sequential schedule of oxaliplatin on day I and topotecan on days 2
      5, in human colon and ovarian cancer cells in vitro, in nude mice bearing human
      cancer xenografts and finally in cancer patients in a phase I trial. RESULTS: We
      demonstrated a supra-additive effect of this combination on inhibition of colony
      formation and induction of apoptosis in vitro. We then demonstrated that the two
      agents in combination markedly inhibit tumor growth in nude mice. We translated
      these results into a clinical setting, conducting a phase I study in cancer
      patients with oxaliplatin 85 mg/m2 on day 1 and topotecan at doses escalating
      from 0.5 to 1.5 mg/m2 on days 2-5. Sixty cycles of treatment were administered to
      18 patients affected prevalently by ovarian and colorectal cancer. Combination
      with topotecan 1.5 mg/m2 caused a dose-limiting toxicity. Therefore the maximum
      tolerated dose of topotecan was 1.25 mg/m2, at which six patients experienced a
      mild hematological and gastrointestinal toxicity. We also obtained evidence of
      clinical activity, particularly in ovarian cancer. CONCLUSIONS: Our results
      provide a solid biological and clinical rationale for a phase II trial at the
      recommended doses of oxaliplatin 85 mg/m2 and topotecan 1.25 mg/m2, possibly in
      ovarian cancer patients.

PMID- 11996470
TI  - Topotecan in combination with carboplatin: phase I trial evaluation of two
      treatment schedules.
AB  - BACKGROUND: Topotecan and cisplatin combinations have shown schedule-dependent
      toxicity, which may in part be due to cisplatin nephrotoxicity. As carboplatin is
      less nephrotoxic and increasingly replacing cisplatin in clinical practice, the
      aim of this study was to define the optimal sequence and dose for topotecan in
      combination with carboplatin. PATIENTS AND METHODS: Two parallel phase I trials,
      with pharmacokinetic studies, were conducted administering carboplatin on day 1
      with topotecan on days 1-5 (schedule A) or days 8-12 (schedule B). repeated every
      3 weeks. RESULTS: Twenty-one patients were treated over two dose levels,
      carboplatin AUC 4 [glomerular filtration rate (GFR) calculated from 51Cr-EDTA
      clearance] with topotecan 0.5 or 0.75 mg/m2. At the first dose level, six
      patients were evaluable for each schedule. With schedule A, from 34 cycles, there
      were two dose reductions and 10 treatment delays due to myelosuppression. With
      schedule B from 25 cycles, there was one reduction and 10 delays. At dose level
      2, both patients in schedule A had dose-limiting neutropenia. In contrast, there
      was no dose-limiting toxicity with schedule B in six patients, although the
      majority of cycles were delayed. CONCLUSION: The combination of topotecan and
      carboplatin using these 3-weekly schedules lead to significant myelotoxicity with
      attendant dose reductions and delays; the optimal scheduling of these agents
      remains to be defined.

PMID- 11996471
TI  - Induction chemotherapy followed by concurrent chemotherapy and definitive high
      dose radiotherapy for patients with locally advanced non-small-cell lung cancer
      (stages IIIa/IIIb): a pilot phase I/II trial.
AB  - BACKGROUND: Overall prognosis of patients with locally advanced non-small-cell
      lung cancer (LAD-NSCLC) is still unfavourable. Different attempts to improve
      treatment results have been made using combinations of chemotherapy and
      radiotherapy. The aim of this pilot phase I/II investigation was to test the
      feasibility and toxicity of a definitive multimodality protocol in patients with
      irresectable NSCLC stages IIIA (N2) and IIIB. PATIENTS AND METHODS: Thirty LAD
      NSCLC patients (stages IIIA/IIIB: 3/27; median age: 54 years, range 34-70;
      male/female: 17/13) who were consecutively enrolled onto our ongoing neoadjuvant
      multimodality protocol from October 1996 to February 1999 remained inoperable
      after induction treatment. Three cycles of cisplatin/etoposide (PE) were followed
      by hyperfractionated accelerated radiotherapy (HF-RTx: 1.5 Gy bid up to a total
      dose of 45 Gy in 3 weeks) concurrent with one cycle of PE. Definitive local
      treatment was completed with a small volume boost of 20 Gy (qd), adding up to a
      total dose of 65 Gy to the primary. Patients were routinely offered prophylactic
      cranial irradiation (PCI; 30 Gy; 2 Gy qd). RESULTS: Overall toxicity of the
      definitive CTx/RTx protocol-the main endpoint of this investigation-turned out to
      be acceptable (oesophagitis grade 3/4: 6/4 patients; pneumonitis grade 3/4: 0/1
      patients; no treatment-related deaths). Actuarial survival at 2 years was 31%
      with a loco-regional control rate of 21%. CONCLUSIONS: This regimen turned out to
      be feasible with acceptable toxicity and will serve as a reference arm in a
      planned randomised trial in stage IIIB NSCLC, testing the value of surgery in
      this setting: preoperative induction CTx/RTx followed by surgery versus
      definitive CTx/RTx.

PMID- 11996472
TI  - Malignant pleural mesothelioma: a phase II trial with docetaxel.
AB  - Current cytotoxic therapy has been of limited benefit to patients with malignant
      pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in
      small series of phase II clinical trials, with disappointing responses.
      Docetaxel, an effective taxane in the treatment of advanced breast cancer and non
      small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2
      every 3 weeks to 30 chemotherapy naive patients with malignant pleural
      mesothelioma in a prospective multi-institutional phase II clinical trial. An
      objective response rate (partial responses) of 10% was documented. Additionally,
      21% of the patients had minor responses (intention-to-treat analysis). Three
      patients died within 2 weeks post-first cycle of therapy, although only one
      patient's death was directly attributed to the investigational drug, whilst in
      the majority of the patients, manageable and treatable toxicities were
      encountered. In this phase II clinical trial, docetaxel proved to be mildly
      effective in the treatment of patients with malignant pleural mesothelioma.

PMID- 11996473
TI  - The feasibility of classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF)
      for pre- and post-menopausal node-positive breast cancer patients in a Belgian
      multicentric trial: a study of consistency in relative dose intensity (RDI) and
      cumulative doses across institutions.
AB  - BACKGROUND: Classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF)
      including oral cyclophosphamide is still considered an important adjuvant
      chemotherapy regimen in patients with early breast cancer (BC). Concern has been
      raised regarding the feasibility of this regimen, especially in postmenopausal
      patients. PATIENTS AND METHODS: 254 pre- and post-menopausal node-positive BC
      patients aged < or = 70 years received six cycles of CMF in the context of a
      Belgian multicentric phase III trial of adjuvant chemotherapy. CMF dose and
      schedule were as follows: cyclophosphamide 100 mg/m2 p.o. on days 1 to 14,
      methotrexate 40 mg/m2 intravenously (i.v.) on days 1 and 8, 5-fluorouracil 600
      mg/ml i.v. on days 1 and 8; cycles q. 28 days. The relative dose intensity (RDI)
      was calculated as the ratio between the delivered DI and the planned DI. We also
      analysed the RDI in two subgroups of patients with age > or = 50 years or < 50
      years. RESULTS: Overall, the percentage of patients ending the six cycles of the
      planned CMF regimen was 90%. The mean RDI achieved in the population of 254
      patients was 90% (range 8% to 129%). The subgroup analysis of patients aged > or
      = 50 years and < 50 years showed that 81% and 76% of patients, respectively,
      received > or = 80% of the planned chemotherapy dose intensity (P = 0.33). No
      statistically significant difference was found between the percentage of patients
      who received a RDI < 80% and the participating institutions (P = 0.50).
      CONCLUSIONS: The classical CMF regimen was a feasible regimen in the context of a
      multicentric trial, in which academic institutions as well as community hospitals
      participated. No substantial differences in RDI and cumulative doses were found
      in relation to a patient's age and the participating institution.

PMID- 11996474
TI  - Human mammaglobin RT-PCR assay for detection of occult breast cancer cells in
      hematopoietic products.
AB  - BACKGROUND: The aim of this study was: (i) to evaluate the sensitivity and
      specificity of mammaglobin as a reverse transcriptase polymerase chain reaction
      (RT-PCR) marker of breast cancer cells; (ii) to determine the incidence of tumor
      cell contamination of hematopoietic samples from patients with breast cancer.
      MATERIALS AND METHODS: A nested RT-PCR assay for mammaglobin was developed.
      Sensitivity was determined by serial dilution assays with breast cancer cell
      lines, human breast cancers and normal breast tissue. Specificity was evaluated
      in hematopoietic samples from healthy volunteers and patients with hematological
      malignancies or solid tumors other than breast cancer. RESULTS: The mammaglobin
      transcript was detected in all 15 breast cancers, one benign breast tumor and
      five normal breast tissues studied, as well as in three breast cancer cell lines,
      in dilutions as low as 10(-8). The transcript was not detected in any of 47
      peripheral blood samples, 15 bone marrow aspirates and 28 peripheral blood
      progenitor cell samples from the three control populations. Mammaglobin mRNA was
      detected in 19 of 78 peripheral blood samples from patients with breast cancer
      starting systemic chemotherapy, as well as in five of 30 repeat samples collected
      before the fourth cycle of treatment. The transcript was also present in six of
      seven bone marrow aspirates from patients with metastatic disease, two of five
      with loco-regional disease, but not in the aspirate of two patients with
      thrombocytopenia and a previous history of breast cancer. CONCLUSIONS: Human
      mammaglobin mRNA is a sensitive and specific marker of breast cancer cells and
      should be further studied as a molecular marker of tumor cell contamination of
      hematopoietic tissues.

PMID- 11996475
TI  - Clinical implications of expression of interleukin-8 related to myometrial
      invasion with angiogenesis in uterine endometrial cancers.
AB  - BACKGROUND: Angiogenesis is essential for development, growth and advancement of
      solid tumors. The tumor-associated macrophage has been recognized among
      inflammatory cells as a candidate for supplying tumor angiogenic factors.
      Interleukin (IL)-8 is assumed to be a macrophage-derived mediator of
      angiogenesis. This prompted us to study the clinical implications of macrophage
      derived angiogenesis in uterine endometrial cancers. PATIENTS AND METHODS: Sixty
      patients underwent curative resection for uterine endometrial cancers. The
      patient prognosis was analyzed with a 48 month survival rate after curative
      resection. In tissue of uterine endometrial cancers, the levels of IL-1alpha, IL
      1beta, tumor necrosis factor-alpha, IL-8, basic fibroblast growth factor,
      vascular endothelial growth factor and platelet-derived endothelial cell growth
      factor were determined by enzyme immunoassay, and the localization and counts of
      microvessels and macrophages were determined by immunohistochemistry. RESULTS:
      There was a significant correlation between microvessel counts and IL-8 levels
      and between infiltrated macrophage counts and IL-8 levels in uterine endometrial
      cancers. Immunohistochemical staining revealed that the localization of IL-8 was
      similar to that of CD68 for macrophages. IL-8 levels were significantly increased
      during myometrial invasion from stage Ia to stages Ib through IV. CONCLUSIONS: IL
      8 might act as an angiogenic switch in myometrial invasion in stage I uterine
      endometrial cancers. Furthermore, IL-8 supplied from infiltrated macrophages
      within and around the tumor might not be a prognostic indicator of advancement,
      but may be associated with myometrial invasion in uterine endometrial cancers.

PMID- 11996476
TI  - A phase II Hoosier Oncology Group study of vinorelbine and estramustine phosphate
      in hormone-refractory prostate cancer.
AB  - BACKGROUND: The purpose was to evaluate the combined anti-microtubular regimen of
      vinorelbine and estramustine phosphate (EMP) in hormone refractory prostate
      cancer. PATIENTS AND METHODS: Weekly vinorelbine 20 mg/m2 (or 15 mg/m2 if a
      history of prior pelvic radiotherapy) was combined with EMP at 280 mg orally tds
      for 3 days (the day before, the day of and the day after vinorelbine infusion).
      After 8 weeks of therapy the combination was given every other week. RESULTS:
      From February 1998 to February 1999, 23 men were enrolled with a median age of 69
      years (range 50-83 years). The median prostate-specific antigen (PSA) at entry
      was 160 ng/ml (range 0-802 ng/ml). A median of 13 weeks of therapy was
      administered and the median follow-up was 14.8 months. Eleven patients (48%) had
      lower extremity edema requiring diuretic therapy, two (9%) had grade 2
      granulocytopenia and four patients [17%; 95% confidence interval (CI) 5% to 39%]
      had a thromboembolic episode. There was no treatment-related mortality. Fifteen
      of 21 patients (71%; 95% CI 49% to 89%) had at least a 50% decrease in the PSA
      for at least 2 months with a median time to serologic progression of 3.5 months
      (range 0.75-10.5 months). One of eight patients (12.5%; 95% CI 0% to 53%) with
      measurable disease had a confirmed partial response. The estimated median
      survival was 15.1 months and the actual one year overall survival was 71% (95% CI
      51% to 88%). CONCLUSIONS: Weekly vinorelbine with short course oral EMP is an
      active regimen as evaluated by rate of PSA response, time to progression and
      median survival. However, the toxicities of EMP, even when given as a short
      course, are still problematic.

PMID- 11996477
TI  - Outpatient treatment with subcutaneous histamine dihydrochloride in combination
      with interleukin-2 and interferon-alpha in patients with metastatic renal cell
      carcinoma: results of an open single-armed multicentre phase II study.
AB  - OBJECTIVES: Histamine inhibits formation and release of monocyte/macrophage
      derived reactive oxygen metabolites and thereby protects natural killer (NK) and
      T cells against oxidative inhibition. Efficacy and safety of histamine, when
      given in combination with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha),
      were evaluated in patients with metastatic renal cell carcinoma (mRCC). PATIENTS
      AND METHODS: Forty-eight mRCC patients were included. The self-administered,
      outpatient regimen included IFN-alpha, 3 MIU s.c., once daily for 1 week,
      followed by up to nine 4 week cycles of IFN-alpha, 3 MIU s.c., days 1-7, weeks 1
      4; interleukin-2, 2.4 MIU/m2 s.c., b.i.d., days 1-5, weeks 1 and 2; and histamine
      dihydrochloride, 1 mg s.c., b.i.d. days 1-5, weeks 1-4. RESULTS: Forty-six
      patients were eligible. Forty-two patients were evaluable for response with four
      partial responses (9% of eligible patients, 10% of evaluable patients). Fifteen
      patients (36%) had stable disease. After subsequent surgery of residual tumours,
      three patients (7%) had no evidence of disease at 14+, 21+ and 21+ months. Median
      survival time for all patients was 16.3 months. One grade 4 toxicity
      (thrombocytopenia) was observed. Most frequent grade 3 toxicities were
      fatigue/malaise (26%), dyspnoe (11%), nausea (9%) and stomatitis (9%). Four
      patients discontinued due to treatment-related toxicity. There were no treatment
      related deaths. CONCLUSIONS: The present combination of histamine with IL-2 and
      IFN-alpha. as self-administered outpatient therapy is a safe and well-tolerated
      regimen. However, histamine does not appear to add efficacy with respect to
      response in this low-dose schedule of IL-2 and IFN-alpha. Whether histamine might
      improve efficacy with higher doses of IL-2 and IFN-alpha requires further
      investigation.

PMID- 11996478
TI  - Risk of therapy-related myelodysplastic syndrome/acute leukemia following high
      dose therapy and autologous bone marrow transplantation for non-Hodgkin's
      lymphoma.
AB  - BACKGROUND: Several recent reports have suggested that patients with non
      Hodgkin's lymphomas (NHL) who undergo autologous stem cell transplantation (ASCT)
      are at increased risk of developing therapy-related myelodysplastic syndrome
      (tMDS) and acute myelogenous leukemia (tAML). PATIENTS AND METHODS: We analyzed
      493 patients with NHL who underwent ASCT at The University of Texas M.D. Anderson
      Cancer Center between January 1990 and August 1999. RESULTS: With a median follow
      up time of 21 months after HDT, 22 patients developed persistent cytopenia in at
      least one cell line with morphologic or cytogenetic evidence of tMDS or tAML.
      Univariate analysis identified prior fludarabine therapy, bone marrow involvement
      with lymphoma, and total body irradiation (TBI) as significant risk factors for
      the development of tMDS/tAML (P <0.05). Multiple logistic regression analysis
      showed that TBI was independently associated with an increased risk of developing
      tMDS/tAML (P <0.01). Further analysis of the patients who received TBI revealed
      that patients receiving TBI in combination with cyclophosphamide and etoposide
      were more likely to develop tMDS/tAML than those who received TBI with
      cyclophosphamide or thiotepa (P <0.01). The median survival of patients
      developing tMDS/tAML was 7.5 months (range 0-32 months). CONCLUSIONS: TBI,
      especially when used in combination with cyclophosphamide and etoposide as the
      pretransplant conditioning regimen, is a significant risk factor for the
      development of tMDS/tAML.

PMID- 11996479
TI  - Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms'
      tumor: a Children's Cancer Group report.
AB  - BACKGROUND: The outcome of children with relapsed Wilms' tumor is poor,
      especially with poor-risk factors such as unfavorable histology, early
      recurrence, previous three-drug therapy, relapse not confined to lungs and
      abdominal relapse following abdominal radiotherapy. We report the overall
      response rate, progression-free survival and overall survival of 11 children with
      relapsed and poor-risk Wilms' tumor following ifosfamide/carboplatin/etoposide
      (ICE) chemotherapy. PATIENTS AND METHODS: ICE therapy consisted of ifosfamide
      1800 mg/m2/day (on day 0-4), carboplatin 400 mg/m2/day (on day 0-1) and etoposide
      100 mg/m2/day (on day 0-4). The median age at diagnosis was 39 months (range from
      13 months to 16 years) and the median time to relapse after initial diagnosis was
      9 months (range 4-72 months). All but one patient had at least one poor
      prognostic feature, with eight patients showing three or four. RESULTS: After ICE
      chemotherapy the number of patients showing a complete response (CR) was three
      (27%) and a partial response (PR) was six (55%). The overall response rate
      (CR+PR) was 82%. Five of the six patients with a PR subsequently achieved a CR
      with further therapy. The 3-year event-free survival and overall survival were
      63.6 +/- 14.5%. CONCLUSIONS: The response rate in children with relapsed and poor
      risk Wilms' tumor is >80% with ICE re-induction chemotherapy followed by post-ICE
      therapy. The optimal approach for post-ICE consolidation therapy has yet to be
      determined.

PMID- 11996480
TI  - Does a drug do better when it is new?
AB  - BACKGROUND: When assessing a new, promising therapeutic approach, a clinician's
      perception of a drug's effectiveness may be shaped by different kinds of
      phenomena, and among them, a favorable attitude towards new treatments, and as a
      result a tendency to overestimate their efficacy (wish bias). MATERIALS AND
      METHODS: A retrospective study of published randomized clinical trials of
      doxorubicin-based chemotherapy for advanced breast cancer was carried out. Global
      (complete plus partial) response rate over time with allowance for type of drug
      regimen (mono- or polychemotherapy) and prior adjuvant therapies was assessed in
      the doxorubicin-containing arm using multivariate logistic regression analysis.
      RESULTS: Twenty-nine studies published from 1975 to 1999 were retrieved for a
      total of 2234 women with advanced breast cancer enrolled in the doxorubicin
      containing arms. There was a significant decrease in response rate to doxorubicin
      as first-line treatment over time that resisted adjustment for important
      differences in therapeutic management [odds ratio for global response = 0.89, 95%
      confidence interval (CI) 0.81 to 0.99]. CONCLUSIONS: Although only one drug
      (doxorubicin) in one clinical context (advanced breast cancer) has been analyzed,
      our findings support the use of double blind methodology whenever possible when
      assessing subjective endpoints and encourage further studies aimed at defining
      the clinical relevance of a wish bias in medicine.

PMID- 11996481
TI  - An explosive course of squamous cell penile cancer in an AIDS patient.
AB  - We report the case of a 37-year-old man in whom penile cancer was discovered
      while he was treated for AIDS 4 years after a human papillomavirus (HSV)
      infection. Despite initially localised disease with T1 N0 staging, he died of
      metastasis within 3 years. A brief review of the literature regarding HPV-related
      cancer in HIV-infected patients is presented and therapeutic options are
      discussed.

PMID- 11996482
TI  - Anaphylactic shock secondary to intravenous administration of folinic acid: a
      first report.
AB  - BACKGROUND: Folates, components of the B-complex vitamins, have numerous
      pharmacological effects. In oncology combining folates with 5-fluorouracil (5-FU)
      enhances the cytotoxic effects of chemotherapy in colon cancer patients. Folic
      acid has been rarely involved in adverse allergic reactions. To the best of our
      knowledge no anaphylactic reaction secondary to folinic acid (FA) administration
      has ever been reported before. PATIENTS AND METHODS: An 80-year-old patient had
      adjuvant chemotherapy for colon cancer including FA and 5-FU and irinotecan as a
      second line agent after multiple metastases. RESULTS: Following FA administration
      anaphylactic shock occurred. Diagnosis was made according to the French method of
      adverse reactions monitoring. CONCLUSION: Anaphylactic shock may be an adverse
      reaction of FA in patients receiving chemotherapy for colon cancer.

PMID- 11996483
TI  - Humoral immune response for early diagnosis of breast carcinoma.

PMID- 11996484
TI  - Incidence of cardiotoxicity with the oral fluoropyrimidine capecitabine is
      typical of that reported with 5-fluorouracil.

PMID- 11996485
TI  - Reply to the article "Editorial comments on 'reduction of chemotherapy-induced
      febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in
      small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase
      III study'", by P. A. Bunn Jr (Ann Oncol 2001; 12: 1339-1340).

PMID- 11996486
TI  - Biological monitoring of pesticide exposure: a review of analytical methods.
AB  - A wide range of studies concerned with analytical methods for biological
      monitoring of exposure to pesticides is reviewed. All phases of analytical
      procedures are assessed, including sampling and storage, sample preparation and
      analysis, and validation of methods. Most of the studies aimed at measuring
      metabolites or unchanged compounds in urine and/or blood as biological indicators
      of exposure or dose. Biological indicators of effect, such as cholinesterase, are
      also evaluated. The principal groups of pesticides are considered:
      organophosphorus pesticides, carbamate pesticides, organochlorine pesticides,
      pyrethroid pesticides, herbicides, fungicides and other compounds. Choice of the
      method for biological monitoring of exposure depends on the study population: a
      detection limit of 1 microg/l or less is required for the general population;
      higher values are adequate for occupationally exposed subjects. Interpretation of
      results is also discussed. Since biological indices of exposure are only
      available for a few compounds, biological reference values, established for the
      general population, may be used for comparison with levels of professionally
      exposed subjects.

PMID- 11996487
TI  - Capillary gas chromatographic determination of 1,4-butanediol and gamma
      hydroxybutyrate in human plasma and urine.
AB  - This article describes two methods for the determination of 1,4-butanediol and
      gamma-hydroxybutyrate in human plasma and urine using capillary gas
      chromatography. For 1,4-butanediol, plasma or urine samples (500 microl) were
      extracted by protein precipitation whereas for gamma-hydroxybutyrate, plasma or
      urine samples (500 microl) were extracted and derivatised with BF3-butanol. The
      compounds were separated on a Supelcowax-10 column and detection was achieved
      using a flame ionization detector. The methods are linear over the specific
      ranges investigated, accurate (with a percentage of the nominal concentration
      <109.8%) and showed intra-day and inter-day precision within the ranges of 5.0
      12.0 and 7.0-10.1%, respectively. No interferences were observed in plasma and
      urine from hospitalized patients.

PMID- 11996488
TI  - Very sensitive and specific determination of sufentanil in human serum applying
      liquid chromatography-two stage mass spectrometry.
AB  - Sufentanil is the most potent synthetic opioid currently in use. Extremely low
      serum concentrations have to be determined for therapeutic drug monitoring and to
      support brain death diagnosis by excluding opioid induced coma. The described
      method utilizes a HPLC-MS-MS system with an electrospray ion source and an ion
      trap mass spectrometer. The serum samples were extracted under basic conditions
      with toluene-2-propanol (10:1, v/v). Chromatographic separation was achieved on a
      RP-18 70x2 mm column with a 0.02% trifluoroacetic acid in a water-acetonitrile
      gradient as mobile phase. The limits of detection and quantification are 3 and 10
      pg/ml, respectively. At the limit of quantification, the intra-day relative
      standard deviation of the assay is 12.6% and the inter-day relative standard
      deviation is 14%.

PMID- 11996489
TI  - Quantitative capillary electrophoresis assay for the proteolytic stability of
      luteinizing hormone-releasing hormones.
AB  - A rapid and simple capillary electrophoresis (CE) assay for measuring the
      stability of luteinizing hormone-releasing hormone (LHRH) analogues in the
      presence of intestinal enzymes has been developed and validated. Buffer pH and
      sample stacking were important factors in controlling resolution and
      reproducibility. The CE assay for human (h) and salmon LHRH analogues between
      0.05 and 0.25 mM was linear for peak height versus concentration (r2>0.99).
      Analysis of hLHRH at 0.1 mM had an intra-day relative standard deviation of 1.25%
      and an inter-day relative standard deviation of 5.0%. The method was applied to
      the stability of LHRH analogues in salmon intestinal digests.

PMID- 11996490
TI  - Rapid screening method for determination of Ecstasy and amphetamines in urine
      samples using gas chromatography-chemical ionisation mass spectrometry.
AB  - The need for analytical screening tests more reliable and valid to detect
      amphetamine and related "designer drugs" in biological samples is becoming
      critical, due to the increasing diffusion of these drugs on the European illegal
      market. The most common screening procedures based on immunoassays suffer a
      number of limitations, including low sensitivity, lack of specificity and limited
      number of detectable substances. This paper describes a screening method based on
      gas-chromatography-mass-spectrometry (GC/MS) using positive chemical ionisation
      (PCI) detection. Methanol was used as reactant gas in the ionisation chamber.
      Molecular ions of different compounds were monitored, allowing a sensitivity of 5
      10 ng/ml with high selectivity. The sensitivity of the method gives positive
      results in samples taken 48-72 h after intake of one dose of 50-100 mg. The
      method is simple and rapid. Sample preparation was limited to one liquid-liquid
      extraction, without any hydrolysis and derivatisation. Hydrolysis is critical to
      identify metabolites excreted as conjugates. Blank urine samples spiked with
      known amounts of amphetamine (AM), methylamphetamine (MA),
      methylenedioxyamphetamine (MDA), methylenedioxymethylamphetamine (MDMA),
      methylenedioxyethylamphetamine (MDEA) and methylenedioxyphenyl-N-methyl-2
      butanamine (MBDB) were analysed. The method was successfully tested on real
      samples of urine from people, whose use of amphetamine was suspected, and results
      were compared with results obtained with immunoassays.

PMID- 11996491
TI  - New simple liquid chromatographic method for the determination of trimethoprim,
      sulfadiazine and N4-acetylsulfadiazine in plasma of broilers.
AB  - A new method for simultaneous quantification of trimethoprim, sulfadiazine and N4
      acetylsulfadiazine in plasma of broilers at levels down to 13-16 ng/ml has been
      developed. Samples were deproteinized with acetonitrile, defatted with hexane,
      and extracted with dichloromethane. Chromatographic analysis was carried out on a
      C18 column in the presence of tetrabutylammonium hydrogen sulfate, a competing
      base, while detection was performed at 240 nm for trimethoprim, and 270 nm for
      both sulfadiazine and N4-acetylsulfadiazine. Accuracy and precision data showed
      recoveries and relative standard deviation values better than 87.3% and 3.1%,
      respectively, for all three analytes. The good analytical characteristics of the
      method could allow limits of detection in the low ng/ml range to be realised. The
      method was successfully applied to determine drug concentrations in plasma
      samples from broilers administered a combination of sulfadiazine and
      trimethoprim.

PMID- 11996492
TI  - Micellar electrokinetic capillary chromatography for the determination of
      fluoxetine and its metabolite norfluoxetine in biological fluids.
AB  - A micellar electrokinetic capillary chromatography (MEKC) for determining
      fluoxetine and its metabolite (norfluoxetine) is proposed. Optimal conditions for
      the quantitative separation were investigated. A background electrolyte solution
      consisting of 5 mM phosphate buffer adjusted to pH 12.3 and 40 mM of 1
      decanesulfonic acid sodium salt (DSS), hydrodynamic injection and 25 kV of
      separation voltage were used. Good linearity and precision were obtained for both
      compounds. Detection limits of 0.2 mg/l for fluoxetine and norfluoxetine were
      obtained. The developed method is rapid and it has been applied to determine
      fluoxetine and its metabolite in human serum and urine. The samples were purified
      and enriched by means of extraction-preconcentration step with a preconditioned
      C18 cartridge and eluting the compounds with methanol.

PMID- 11996493
TI  - High-performance liquid chromatographic assay for alpha-lipoic acid and five of
      its metabolites in human plasma and urine.
AB  - An isocratic reversed-phase HPLC method for the simultaneous quantitation of
      alpha-lipoic acid and five of its metabolites in human plasma as well as in human
      urine employing solid-phase extraction and pulsed amperometric detection was
      developed and validated. The method was found to be sufficiently precise and
      accurate for the measurement of alpha-lipoic acid and its metabolites 6,8
      bis(methylthio)octanoic acid, 4,6-bis(methylthio)hexanoic acid and 2,4
      bis(methylthio)butanoic acid in plasma and urine samples, obtained from patients
      suffering from diabetic neuropathy as well as from healthy volunteers following
      daily oral administration of 600 mg alpha-lipoic acid. The quantitation of the
      metabolite bisnorlipoic acid was often impaired by interferences caused by an
      unidentified metabolite. However, bisnorlipoic acid was detected in few test
      samples and the concentrations were consistently low. Despite the poor recovery
      of the metabolite tetranorlipoic acid from plasma, reproducibility and accuracy
      were found to be from acceptable magnitude to assess concentration time courses.
      Thus, the obtained analytical results are considered as reliable and well suited
      for pharmacokinetic studies of alpha-lipoic acid and its metabolites.

PMID- 11996494
TI  - Nucleotide adsorption-desorption behaviour of boronic acid functionalized uniform
      porous particles.
AB  - In this study, nucleotide adsorption-desorption behaviour of boronic acid
      carrying uniform, porous particles was investigated. The particles were produced
      by a "multi-step microsuspension polymerization" in the form of poly(styrene
      vinylphenyl boronic acid-divinylbenzene) terpolymer. In the first step of the
      production method, uniform polystyrene latex particles (6.2 microm in size) were
      obtained by dispersion polymerization. These particles were first swollen by a
      low molecular mass organic agent (i.e. dibutylphthalate, DBP) and then by a
      monomer mixture including styrene (S), 4-vinylphenyl boronic acid (VPBA) and
      divinylbenzene (DVB). The particle uniformity was protected in both swelling
      stages by adjusting DBP/polystyrene latex and monomer mixture/polystyrene latex
      ratios. Polymerization of the monomer mixture in the swollen seed particles
      provided boronic acid-carrying uniform, porous particles 11-12 microm in size. To
      have uniform particles with different porosities and boronic acid contents, the
      feed concentration of boronic acid-carrying monomer and the monomer/seed latex
      ratio were changed. The particles were tried as sorbent for the adsorption of a
      model nucleotide (i.e., beta-nicotinamide adenine dinucleotide, beta-NAD). In the
      beta-NAD adsorption experiments, the maximum equilibrium adsorption was obtained
      at pH 8.5 which was very close to pKa of boronic acid. The incorporation of
      boronic acid functionality provided a significant increase in the beta-NAD
      adsorption. In contrast to plain poly(styrene-co-divinylbenzene) particles, four
      fold higher beta-NAD adsorption was obtained with the boronic acid functionalized
      particles. Beta-NAD was desorbed from the particles with the yields higher than
      90% by weight.

PMID- 11996495
TI  - Determination of delavirdine in very small volumes of plasma by high-performance
      liquid chromatography with fluorescence detection.
AB  - Delavirdine is a newly developed anti-HIV-1 drug for AIDS therapy. This study
      describes a sensitive high-performance liquid chromatographic method for the
      determination of delavirdine in 50 microl of plasma. Samples were deproteinized
      with 150 microl of a solution of internal standard (cisapride 10 microg/ml) in
      acetonitrile. An aliquot of the supernatant was injected onto the column. HPLC
      separation was achieved on a C18 column with the mobile phase of acetonitrile-50
      mM sodium dihydrogen phosphate (60:40, v/v) at a flow-rate of 1 ml/min. The
      eluants were measured by fluorescence detection with excitation at 295 nm and
      emission filtration at 425 nm. The retention time was about 5.3 min for
      delavirdine and 6.5 min for cisapride. The specificity was demonstrated, as there
      were no interferences from plasma samples of different batches in the regions of
      peak interest. Calibration curves were linear from 25 to 25000 ng/ml. The limit
      of quantitation was 25 ng/ml. The within- and between-day precision (C.V.) was
      9.3%, or less, and the accuracy was within 9.2% of the nominal concentration. The
      small sample volume needed is especially advantageous for the application both in
      pharmacokinetic studies in HIV-infected adults and pediatric patients, and in
      small animals, where limited samples are available.

PMID- 11996496
TI  - Simultaneous determination of fluoxetine and its metabolite p
      trifluoromethylphenol in human liver microsomes using a gas chromatographic
      electron-capture detection procedure.
AB  - An gas chromatography-electron-capture detection method has been developed for
      simultaneous determination of fluoxetine and p-trifluoromethylphenol (TFMP), an O
      dealkylated metabolite of fluoxetine in human liver microsomes. Prior to the
      analysis, aliquots of alkalinized microsomal mixture were extracted with ethyl
      acetate solvent containing acetonitrile (10%, v/v) and the derivatizing reagent,
      pentafluorobenzenesulfonyl chloride (0.1%, v/v). The organ phase was retained and
      taken to dryness, the residue was reconstituted in methanol, and the aliquot of
      extracts was injected directly into a gas chromatograph equipped with an electron
      capture detector. 2,4-Dichlorophenol was added to the initial incubation mixture
      and carried through the procedure as the internal standard. The method provided
      the mean recoveries of up to 103% for fluoxetine and 104% for TFMP. Acceptable
      relative standard deviations were found for both within-run and day-to-day
      assays. The practical limit of detection (signal-to-noise ratio=3) was 1.62 ng/ml
      for TFMP and 6.92 ng/ml for fluoxetine in human liver microsomes, and the limit
      of quantitation was 8.1 pg for TFMP and 34.6 pg for fluoxetine. The assay is
      rapid and sensitive and has been applied successfully to simultaneous
      quantification of fluoxetine and TFMP in human liver microsomes with different
      CYP2C19 genotypes.

PMID- 11996497
TI  - High-performance liquid chromatography with electrochemical detection applied to
      the analysis of 3,4-dihydroxymethamphetamine in human plasma and urine.
AB  - Metabolic activation in the disposition of 3,4-methylenedioxymethamphetamine
      (MDMA, "ecstasy") has been implicated in some of its pharmacological and
      toxicological effects, with the major metabolite 3,4-dihydroxymethamphetamine
      (HHMA) as a putative toxicant through the formation of thioether adducts. We
      describe the first validated method for HHMA determination based on acid
      hydrolysis of plasma and urine samples, further extraction by a solid-phase
      strong cation-exchange resin (SCX, benzenesulfonic acid), and analysis of
      extracts by high-performance liquid chromatography with electrochemical
      detection. The chromatographic separation was performed in an n-butyl-silane (C4)
      column and the mobile phase was a mixture of 0.1 M sodium acetate containing 0.1
      M 1-octanesulphonic acid and 4 mM EDTA (pH 3.1) and acetonitrile (82:18, v/v).
      Compounds were monitored with an electrochemical cell (working potentials 1 and
      2, +0.05 and +0.35 V, respectively, gain 60 microA). A mobile phase conditioning
      cell with a potential set at +0.40 V was connected between the pumping system and
      the injector. Calibration curves were linear within the working concentration
      ranges of 50-1000 microg/L for urine and plasma. Limits of detection and
      quantification were 10.5 and 31.8 microg/L for urine and 9.2 and 28.2 microg/L
      for plasma. Recoveries for HHMA and DHBA (3,4-dihydroxybenzylamine, internal
      standard) were close to 50% for both biological matrices. Intermediate precision
      and inter-day accuracy were within 3.9-6.5% and 7.4-15.3% for urine and 5.0-10.8%
      and 9.2-13.4% for plasma.

PMID- 11996498
TI  - Proteomic analysis of rat soleus and tibialis anterior muscle following
      immobilization.
AB  - A proteomic analysis was performed comparing normal slow twitch type fiber rat
      soleus muscle and normal fast twitch type fiber tibialis anterior muscle to
      immobilized soleus and tibialis anterior muscles at 0.5, 1, 2, 4, 6, 8 and 10
      days post immobilization. Muscle mass measurements demonstrate mass changes
      throughout the period of immobilization. Proteomic analysis of normal and
      atrophied soleus muscle demonstrated statistically significant changes in the
      relative levels of 17 proteins. Proteomic analysis of normal and atrophied
      tibialis anterior muscle demonstrated statistically significant changes in the
      relative levels of 45 proteins. Protein identification using mass spectrometry
      was attempted for all differentially regulated proteins from both soleus and
      tibialis anterior muscles. Four differentially regulated soleus proteins and six
      differentially regulated tibialis anterior proteins were identified. The
      identified proteins can be grouped according to function as metabolic proteins,
      chaperone proteins, and contractile apparatus proteins. Together these data
      demonstrate that coordinated temporally regulated changes in the proteome occur
      during immobilization-induced atrophy in both slow twitch and fast twitch fiber
      type skeletal muscle.

PMID- 11996499
TI  - Rapid and sensitive determination of sertraline in human plasma using gas
      chromatography-mass spectrometry.
AB  - A method for the determination of sertraline in human plasma using gas
      chromatography-mass spectrometry (GC-MS), with the selected ion-monitoring (SIM)
      mode, was described. The following was used in this study: (1) single liquid
      liquid extraction at alkaline pH after deproteinization of plasma protein and (2)
      perfluoroacylation with HFBA, which has higher sensitivity (about 10-fold)
      compared with previous reported derivatization. The detection limit for the SIM
      of sertraline as an N-HFB derivative was 0.1 ng/ml, and its recovery was 80-85%.
      The linear response was obtained in the range of 0.2-10.0 ng/ml with a
      correlation coefficient of 0.999. The coefficient of variation (C.V.%) was less
      than 12.1% in the 1-30 ng/ml, and less than 18.2% at 0.2 ng/ml, and the accuracy
      was less than 10% at all of the concentration range. These findings indicate that
      this assay method has adequate precision and accuracy to determine the amount of
      sertraline in human plasma. After pharmacokinetics was performed with this assay
      method following oral administration of sertraline hydrochloride in man, moment
      analysis revealed that pharmacokinetic parameters for sertraline (Cmax, 10.3
      ng/ml; Tmax, 8.0 h; T(1/2) 28.6 h) were similar to previously reported results.
      These results indicate that this simple and sensitive assay method is readily
      applicable to the pharmacokinetic studies of sertraline.

PMID- 11996500
TI  - Extraction and separation of urinary catecholamines as their diphenyl boronate
      complexes using C18 solid-phase extraction sorbent and high-performance liquid
      chromatography.
AB  - The clinical utility of a one-step extraction procedure based on the retention of
      a diphenyl boronate-catecholamine complex on a C18 solid-phase extraction sorbent
      was investigated for the measurement of urinary catecholamines. Although
      recoveries with the extraction procedure were optimal over a relatively broad pH
      range (7.5-9.5), analytical factors such as sample loading and elution flow
      rates, wash step and elution conditions, the concentration of catecholamines in
      urine to be extracted and the type of C18 sorbent used for extraction were found
      to influence the efficiency of this procedure and would therefore need to be
      controlled for optimal recoveries. Under optimal conditions the recovery of
      noradrenaline, adrenaline and dopamine from spiked urine was high and
      reproducible (mean recoveries were >85% for all catecholamines). The
      effectiveness of sample clean-up step was demonstrated by reverse phase, ion pair
      high-performance liquid chromatography with electrochemical detection. The method
      described was found to be suitable for the routine measurement of catecholamines
      in urine in clinical biochemistry laboratories. It has a high sample extraction
      throughput (40/h) and has adequate precision (between batch CV<8%) and
      sensitivity (LOD<30 nmol/l; LOQ<65 nmol/l) for all the catecholamines measured.
      The method has acceptable accuracy, showing a mean bias of 6.6% for
      noradrenaline, 7.3% for adrenaline and 6.8% for dopamine from the mean value of
      laboratories (N=69) participating in an External Quality Assurance scheme for
      greater than 12 months.

PMID- 11996501
TI  - Determination of diclofenac in rat bile and its interaction with cyclosporin A
      using on-line microdialysis coupled to liquid chromatography.
AB  - Diclofenac is a potent inhibitor of prostaglandin synthesis, as well as an
      established antipyretic and analgesic agent. To determine diclofenac in rat bile
      and investigate its hepatobiliary excretion, a procedure using rapid and
      sensitive high-performance liquid chromatography coupled to microdialysis
      sampling system was developed. A shunt linear microdialysis probe was inserted
      into the common bile duct between the liver and the duodenum for continuous
      sampling of the drug from bile fluids following intravenous administration of
      diclofenac (1 mg/kg). Separation and quantitation of diclofenac in the bile
      dialysates were achieved using a microbore reversed-phase C18 column (150x1.0 mm
      I.D.; particle size 5 microm) maintained at ambient temperature. Samples were
      eluted with a mobile phase containing 100 mM sodium dihydrogenphosphate (pH 3.1)
      acetonitrile (30:70, v/v), and the flow-rate of the mobile phase was 0.05 ml/min.
      The UV detector wavelength was set at 280 nm. The concentration-response
      relationship from the present method indicated linearity (r2>0.995) over a
      concentration range of 5-5000 ng/ml for diclofenac. Intra-assay and inter-assay
      precision and accuracy of diclofenac fell well within the predefined limits of
      acceptability (< or = 15%). The diclofenac in rat bile appeared to have a slow
      elimination phase, with a peak concentration at 20 min following diclofenac
      administration. The results demonstrated that diclofenac might be secreted into
      bile in unconjugated form by a canalicular bile acid transporter, and then go
      through hepatobiliary excretion. These results may provide good clinical evidence
      showing the value of diclofenac for the treatment of biliary colic. The
      elimination half-life of diclofenac in the biliary elimination was prolonged by
      treatment with cyclosporin A, indicating that the drug-drug interaction might
      affect the hepatobiliary excretion of diclofenac.

PMID- 11996502
TI  - On-line solid-phase extraction and determination of paclitaxel in human plasma.
AB  - The application of coupled-column liquid chromatographic analysis to
      pharmacokinetic studies eliminates the need for sample clean-up from plasma.
      Considering lipophilic antineoplastic agents, we tested this approach to analyze
      paclitaxel under unfavourable circumstances (i.e., weekly low-dose regimen,
      plasma protein binding >90%, UV detection at 229 nm). The excellent quality
      control data (recovery: 95.6-100.7%, inter-assay relative standard deviation on 5
      days: 1.3-3.2%, accuracy: 0.9-2.7%) and the detection limit of 19 nM indicates
      the usefulness of this method for the analysis of paclitaxel in plasma using on
      line solid-phase extraction.

PMID- 11996503
TI  - Combined use of micro-preparative gel electrophoresis and reversed-phase high
      performance liquid chromatography for purification of amyloid beta peptides
      deposited in brains of Alzheimer's disease patients.
AB  - A new micro-technique is developed for purification of amyloid beta peptides (A
      beta) extracted from brain tissues of patients with Alzheimer's disease (AD). It
      includes SDS-polyacrylamide gel electrophoresis of the extracted brain tissue
      material, electroblotting onto supporting membranes, and reversed-phase HPLC of
      the proteins eluted from membranes. By this technique, the extracted A beta are
      first separated electrophoretically from the higher and lower molecular mass
      tissue components, and then purified by reversed-phase HPLC from the contaminants
      having similar molecular masses, but different retention times on the column. In
      contrast to the common large-scale isolation procedures employing density
      gradient centrifugation, enzymatic digestions and size-exclusion chromatography,
      the developed micro-technique might be applied for biochemical analysis of A beta
      contained in small AD brain tissue specimens.

PMID- 11996504
TI  - Cytochrome p450 and parkinsonism: protective role of CYP2E1.

PMID- 11996505
TI  - Cell cycle progression towards Alzheimer's disease.

PMID- 11996506
TI  - Involvement of nicotinic acetylcholine receptors in the protection of dopamine
      terminals in experimental parkinsonism.

PMID- 11996507
TI  - A preclinical re-evaluation of the safety profile of tolcapone.

PMID- 11996508
TI  - COMT inhibition and safety.

PMID- 11996509
TI  - Correlates of experimental brain ischemia: quantified EEG analysis.

PMID- 11996510
TI  - Receptor and post-receptor mechanisms of ischemic long-term potentiation in the
      striatum.

PMID- 11996511
TI  - Apomorphine as a neuroprotective drug: a study in MPTP-treated mice and potential
      relevance to ischemia.

PMID- 11996512
TI  - Mitochondria and oxidative damage in amyotrophic lateral sclerosis.

PMID- 11996513
TI  - Advances in understanding the pathogenetic mechanisms of Alzheimer's disease.

PMID- 11996514
TI  - Amyotrophic lateral sclerosis and SOD1 gene: an overview.

PMID- 11996515
TI  - Copper-dependent oxidative stress, alteration of signal transduction and
      neurodegeneration in amyotrophic lateral sclerosis.

PMID- 11996516
TI  - Recent advances in the therapy of amyotrophic lateral sclerosis: focus on
      excitotoxicity.

PMID- 11996517
TI  - Novel regulators of the in vitro release of hypothalamic corticotrophin-releasing
      hormone two decades after its discovery: a review.

PMID- 11996518
TI  - Endotoxin, prostanoids and corticotrophin-releasing hormone: an integrated view.

PMID- 11996519
TI  - Drug addiction and memory systems: how neutral stimuli can gain control of
      behaviour.

PMID- 11996520
TI  - Harmful effects of substance abuse: a Darwinian perspective.

PMID- 11996521
TI  - Spinal muscular atrophy of childhood at the edge of the centuries.

PMID- 11996522
TI  - Dystrophinopathies: peculiar clinical and laboratory aspects.

PMID- 11996523
TI  - The Siena experience on rare neurological diseases: diagnosis, therapy and
      research model for investigations of central and peripheral nervous systems and
      muscle.

PMID- 11996524
TI  - The relevance of cytokines within the immuno-inflammatory response: are they
      reliably measurable in biological fluids?

PMID- 11996525
TI  - The immunotherapy of cancer and tumor escape from immune surveillance.

PMID- 11996526
TI  - Experimental findings in primary glioma cell cultures.

PMID- 11996527
TI  - Searching for molecular markers of human gliomas.

PMID- 11996528
TI  - The HIV-1 envelope protein, gp120, causes neuronal apoptosis in the neocortex of
      the adult rat: a useful experimental model to study neuroaids.

PMID- 11996529
TI  - Biological markers of neurotoxic diseases.

PMID- 11996530
TI  - Environmental neurotoxicity in humans: principles of diagnosis, effects and
      selected case examples.

PMID- 11996531
TI  - Endogenous cannabinoids in neuronal and immune cells: toxic effects, levels and
      degradation.

PMID- 11996532
TI  - Heterogeneity in migraine: many genes for many phenotypes?

PMID- 11996533
TI  - Nitric oxide-induced neuronal activation in the central nervous system as an
      animal model of migraine: mechanisms and mediators.

PMID- 11996534
TI  - Trigeminal pain pathway: peripheral and central activation as experimental models
      of migraine.

PMID- 11996535
TI  - Advances in the genetics of spinocerebellar ataxias.

PMID- 11996536
TI  - Current perspectives in the treatment of mitochondrial DNA diseases.

PMID- 11996537
TI  - The role of the subthalamic nucleus in the pathophysiology of Parkinson's
      disease.

PMID- 11996539
TI  - Experimental investigation on the formation of carbon-bearing molecules in the
      interstellar medium via neutral-neutral reactions.

PMID- 11996538
TI  - Organometallic chemistry on silicon and germanium surfaces.

PMID- 11996540
TI  - Aryl-aryl bond formation one century after the discovery of the Ullmann reaction.

PMID- 11996541
TI  - Nonlinear signal analysis methods in the elucidation of protein sequence
      structure relationships.

PMID- 11996542
TI  - Enantiomerically pure planar chiral organometallic complexes via facially
      selective pi-complexation.

PMID- 11996543
TI  - Current trends in patterning with copper.

PMID- 11996544
TI  - Selective alkane transformations via radicals and radical cations: insights into
      the activation step from experiment and theory.

PMID- 11996545
TI  - Bonding in ground-state and excited-state A+.Rg van der Waals ions (A = atom, Rg
      = rare-gas atom): a model-potential analysis.

PMID- 11996546
TI  - Azidonucleosides: synthesis, reactions, and biological properties.

PMID- 11996548
TI  - Ru-, Rh-, and Pd-catalyzed C-C bond formation involving C-H activation and
      addition on unsaturated substrates: reactions and mechanistic aspects.

PMID- 11996547
TI  - Chemistry and biology of the tetrahydroisoquinoline antitumor antibiotics.

PMID- 11996549
TI  - Additions to metal-activated organonitriles.

PMID- 11996551
TI  - Molecular imprinting of enzymes with water-insoluble ligands for nonaqueous
      biocatalysis.
AB  - Attaining higher levels of catalytic activity of enzymes in organic solvents is
      one of the major challenges in nonaqueous enzymology. One of the most successful
      strategies for enhancing enzyme activity in organic solvents involves tuning the
      enzyme active site by molecular imprinting with substrates or their analogues.
      Unfortunately, numerous imprinters of potential importance are poorly soluble in
      water, which significantly limits the utility of this method. In the present
      study, we have developed strategies that overcome this limitation of the
      molecular-imprinting technique and that thus expand its applicability beyond
      water-soluble ligands. The solubility problem can be addressed either by
      converting the ligands into a water-soluble form or by adding relatively high
      concentrations of organic cosolvents, such as tert-butyl alcohol and 1,4-dioxane,
      to increase their solubility in the lyophilization medium. We have succeeded in
      applying both of these strategies to produce imprinted thermolysin, subtilisin,
      and lipase TL possessing up to 26-fold higher catalytic activity in the acylation
      of paclitaxel and 17beta-estradiol compared to nonimprinted enzymes. Furthermore,
      we have demonstrated for the first time that molecular imprinting and salt
      activation, applied in combination, produce a strong additive activation effect
      (up to 110-fold), suggesting different mechanisms of action involved in these
      enzyme activation techniques.

PMID- 11996552
TI  - Guanidine is a Zn(2+)-binding ligand at neutral pH in aqueous solution.
AB  - We have found the first well-characterized coordination of guanidine with Zn(2+)
      in a 1:1 complex (ZnL(1)) with cyclen (= 1,4,7,10-tetraazacyclododecane)
      functionalized with guanidinylethyl group (L(1) = (2-guanidinyl)ethyl-cyclen).
      The X-ray structure analysis of the 1:1 complex crystallized at pH 7.5 revealed
      an apical coordination of the pendant guanidinyl group to Zn(2+) ion in ZnL(1).
      By potentiometrtic pH titration, initial formation of a 1:1 Zn(L(1).H(+)) complex
      was indicated, where only the cyclen N's bind to Zn(2+) with the complexation
      constant, log K(s) (K(s) = [Zn(L(1).H(+))]/[Zn(2+)][L(1).H(+)] (M(-1))), being
      12.4 +/- 0.1. Facile deprotonation of the guanidinium pendant in the
      Zn(L(1).H(+)) occurred with a pK(a) value of 5.9 +/- 0.1 at 25 degrees C with I =
      0.1 (NaNO(3)) to yield the guanidine-coordinating complex ZnL(1). 4-Nitrophenyl
      phosphate dianion (NPP(2-)) interacted with ZnL(1) through a new Zn(2+)-phosphate
      coordination, as indicated by (31)P NMR titration and potentiometric pH
      titration. An apparent complexation constant for this new species, log
      K(app)(Zn(L(1).H(+))-NPP), was 4.0 +/- 0.1, which is larger than the log
      K(app)(ZnL(2)-NPP) value of 3.1 for the 1:1 complex of Zn(2+)-cyclen (ZnL(2))
      with NPP at the common pH 5.6. The interaction of ZnL(1) with a phosphate dianion
      was proven by the X-ray crystal structure analysis of the 1:1 ZnL(1)-PP(2-)
      complex (PP(2-) is a dianion of phenyl phosphate) obtained from an aqueous
      solution at pH 6.5. At higher pH, the pendant guanidinium cation is deprotonated
      to displace the phosphate to yield the Zn(2+)-guanidine bond.

PMID- 11996553
TI  - Bridgehead carbocations via carbene fragmentation: erasing a 10(10) kinetic
      preference.
AB  - 1-Norbornyloxychlorocarbene (1-NorOCCl), 1-bicyclo[2.2.2]octyloxychlorocarbene (1
      BcoOCCl), and 1-adamantyloxychlorocarbene (1-AdOCCl) were generated in
      dichloroethane (DCE) by photolysis of the appropriate diazirines. The exclusive
      product in each case was the bridgehead alkyl chloride formed by fragmentation of
      the carbene to [R(+) OC Cl(-)] ion pairs, loss of CO, and cation-anion collapse.
      In mixtures of methanol and DCE, each carbene gave three products: RCl, ROH, and
      ROMe. RCl and ROMe resulted from competition between ion pair collapse and
      methanol capture of the cation. ROH resulted from methanol capture of the carbene
      (before fragmentation), followed by eventual methanolysis and hydrolysis of
      ROCH(Cl)OMe. The ratios of carbene capture to carbene fragmentation fell in the
      order 1-NorOCCl > BcoOCCl > 1-AdOCCl; 1-Nor(+) was the least stable cation and
      the slowest to form by fragmentation, so that this carbene was the most readily
      captured. This trend was accentuated in methanol-pentane mixtures, where ionic
      fragmentation was further slowed in the less polar solvent. Laser flash
      photolysis with either UV or time-resolved infrared (TRIR) monitoring permitted
      the determination of the absolute rate constants for fragmentations of the
      carbenes in DCE at 25 degrees C. The rate constants (s(-1)) were: 1-NorOCCl (3.3
      x 10(4)), 1-BcoOCCl (1.5 x 10(5)), and 1-AdOCCl (5.9 x 10(5)). The rate constants
      decreased in the order of increasing strain in the resulting bridgehead
      carbocation, but the range of rate constants was compressed to a factor of only
      approximately 18. This constrasts with the factor of 10(10) by which the
      acetolysis of 1-AdOTs at 70 degrees C exceeded that of 1-NorOTs. The
      fragmentation of 1-NorOCCl to the ion pair was 3 x 10(15) times faster than the
      acetolysis of 1-NorOTs. The activation energies were measured as 9.0 kcal/mol
      (log A = 11.2 s(-1)) for the fragmentation of 1-NorOCCl and 4.4 kcal/mol (log A =
      8.44 s(-1)) for that of 1-BcoOCCl both in DCE. B3LYP/6-31G computed activation
      energies in simulated DCE were 14.6 and 2.7 kcal/mol, respectively.

PMID- 11996554
TI  - Novel approach for catalytic cyclopropanation of alkenes via (2-furyl)carbene
      complexes from 1-benzoyl-cis-1-buten-3-yne.
AB  - The reaction of conjugated ene-yne-ketones 3 with a variety of alkenes in the
      presence of a catalytic amount of Cr(CO)(5)(THF) at room temperature gives (2
      furyl)cyclopropanes in good yields. These cyclopropanation reactions proceed via
      (2-furyl)carbene-chromium intermediates 4 formed in situ from ene-yne-ketones 3.
      Late transition metals, such as [RuCl(2)(CO)(3)](2), [RhCl(cod)](2), PdCl(2), and
      PtCl(2), also catalyze effectively the cyclopropanation of styrene with 3.

PMID- 11996555
TI  - Dramatic improvement of the enantiomeric excess in the asymmetric conjugate
      addition reaction using new experimental conditions.
AB  - The asymmetric conjugate addition of dialkylzincs is usually performed with
      Cu(OTf)(2) in toluene. We show that by using a copper carboxylate in Et(2)O, THF,
      or EtOAc, we strongly improve the enantioselectivity with a given ligand. Ee
      values up to 99.1% could be reached with new ligands based on the induced
      atropisomerism of a simple biphenol unit. In addition, we show that the Lewis
      acid effect of Cu(OTf)(2) is not a significant.

PMID- 11996556
TI  - Predicting gas transport in formed zeolite adsorbents from NMR studies.
AB  - The self-diffusion of nitrogen, methane, and carbon monoxide within a 5A zeolitic
      adsorbent has been examined with use of pulsed field gradient (PFG) NMR. In all
      cases, the diffusion process is well-described by a refined version of the long
      range diffusion model (LRDM), adapted here for use with pelletized adsorbents,
      which uses exclusively adsorbent porosity and isotherm data as inputs.
      Correlation of the experimental data with this model yields tortuosity factors
      that are characteristic of the adsorbate and reflect the longer diffusive path a
      molecule must take due to the winding nature of the pore structure. It is
      demonstrated that the diffusion model can be used to accurately predict the
      diffusion coefficients for a ternary gas mixture within a 5A zeolite. To fully
      characterize the diffusive process, the surface excess on the PFG NMR samples has
      been obtained by a novel gas-phase NMR technique that is well-suited for
      measuring pure and multicomponent isotherms.

PMID- 11996557
TI  - Lithium-sulfoxide-lithium exchange for the asymmetric synthesis of atropisomers
      under thermodynamic control.
AB  - Ortholithiation and reaction with (-)-menthyl p-toluenesulfinate introduces a
      sulfoxide substituent ortho to the stereogenic Ar-CO axis of an aromatic amide.
      The sulfoxide exerts a powerful conformational bias on the axis, such that after
      rapid equilibration at ambient temperature essentially only one of two
      diastereoisomeric Ar-CO atropisomers is populated. Sulfoxide-lithium exchange by
      treatment with t-BuLi regenerates the ortholithiated amide in an enantiomerically
      pure and conformationally stable form. Rapid electrophilic trapping of the
      organolithium therefore generates highly enantiomerically enriched atropisomeric
      tertiary aromatic amides. The overall process, involving temporary substitution
      of lithium to sulfoxide to lithium, amounts to a dynamic resolution under
      thermodynamic control.

PMID- 11996558
TI  - Functional expression of genes involved in the biosynthesis of the novel
      polyketide chain extension unit, methoxymalonyl-acyl carrier protein, and
      engineered biosynthesis of 2-desmethyl-2-methoxy-6-deoxyerythronolide B.
AB  - A subcluster of five genes, asm13-17, from the ansamitocin biosynthetic gene
      cluster of Actinosynnema pretiosum was coexpressed in Streptomyces lividans with
      the genes encoding the 6-deoxyerythronolide B (6-DEB) synthase from
      Saccharopolyspora erythraea, in which the methylmalonate-specifying AT6 domain
      had been replaced by the methoxymalonate-specifying AT8 domain from the FK520
      cluster of Streptomyces hygroscopicus. The engineered strain produced the
      predicted product, 2-desmethyl-2-methoxy-DEB, instead of 6-DEB and 2-desmethyl-6
      DEB, which were formed in the absence of the asm13-17 cassette, indicating that
      asm13-17 are sufficient for synthesis of this unusual chain extension unit.
      Deletion of asm17, encoding a methyltransferase, from the cassette gave 6-DEB
      instead of its hydroxy analogue, indicating that methylation of the extender unit
      is required for its incorporation.

PMID- 11996559
TI  - An unusual dimeric structure of a Cu(I) bis(thiosemicarbazone) complex:
      implications for the mechanism of hypoxic selectivity of the Cu(II) derivatives.
AB  - The electrochemical reduction of Cu(II) bis(thiosemicarbazone) complexes
      [Cu(II)(btsc)] is accompanied by protonation to give an unstable Cu(I)
      intermediate [Cu(btscH(2))](+). The nature of this intermediate was probed by
      reaction of bis(thiosemicarbazone) ligands with a Cu(I) precursor which gave a
      novel helical dimeric dicationic complex. The dependence of these reactions on
      the ligand backbone substituents is discussed together with their possible
      relevance to the use of Cu(II) bis(thiosemicarbazone) ligands as hypoxic
      selective imaging and therapeutic agents.

PMID- 11996560
TI  - Catalytic copolymerization of CO and ethylene with a charge neutral palladium(II)
      zwitterion.
AB  - The synthesis of a zwitterionic Pd(II) complex supported by an anionic
      bis(phosphino)borate ligand, Ph(2)B(CH(2)PPh(2))(2) (abbreviated as
      [Ph(2)BP(2)]), is reported. The new complex, [Ph(2)BP(2)]PdMe(THF), is active for
      CO and ethylene copolymerization. The copolymerization activity and polyketone
      molecular weight for the neutral, zwitterionic system are compared with those for
      the cationic systems [R(2)E(CH(2)PPh(2))(2)PdMe(THF)][B(C(6)F(5))(4)] where ER(2)
      = SiPh(2) and CH(2). Surprisingly, the more electron rich zwitterionic system is
      a catalyst of activity comparable to that of the more conventional cationic
      systems.

PMID- 11996561
TI  - Self-organization of supramolecular complex composed of rigid dendritic porphyrin
      and fullerene.
AB  - A second-generation 1,3,5-phenylene-based dendritic porphyrin decorated with
      flexible alkyl chains exhibited a liquid crystallinity, and the inclusion of
      fullerene within the nanospace of the dendritic porphyrin strongly affected the
      mesophase structure in the thermotropic liquid-crystalline phase.

PMID- 11996562
TI  - Facilitated phospholipid flip-flop using synthetic steroid-derived translocases.
AB  - Cholate esters with phenylurea groups at the 7alpha- and 12alpha-positions are
      highly effective promoters of phosphatidylcholine translocation across vesicle
      and cell membranes. The urea groups are essential for strong binding of the
      highly polar phosphate portion of the phosphocholine headgroup and apparently
      cannot be replaced by simple amide, alcohol, or amine moieties. NMR and UV
      studies show that these synthetic translocases have very weak affinity for
      phosphatidylethanolamine and phosphatidylserine.

PMID- 11996563
TI  - Discovery of new fluorescent materials from fast synthesis and screening of
      conjugated polymers.
AB  - A combinatorial approach was developed for the synthesis and the screening of a
      large variety of conjugated polymers. The parallel synthesis of 96
      polyaryleneethynylene derivatives was performed on a 12 x 8 format from diethynyl
      and dibromoaryl building blocks, via a palladium-catalyzed carbon-carbon coupling
      reaction. The qualitative distinction between fluorescent and nonfluorescent
      polymers as well as between the different emission colors were obtained from a
      simple visual test or via a 96-well plate reader spectrofluorimeter. New solid
      state blue-emitting polymers were detected.

PMID- 11996564
TI  - Magnetoelectrochemistry of gold nanoparticle quantized capacitance charging.
AB  - Magnetoelectrochemical studies of gold nanoparticle quantized capacitance
      charging were carried out at ambient conditions. The single electron transfer
      responses were found to be sensitive to external magnetic fields, reflected in
      the enhancement of voltammetric peak currents and shifts of peak formal
      potentials with increasing magnetic field intensities. Additionally, splittings
      of voltammetric peaks were also observed upon the application of an external
      magnetic field. These phenomena might be partly attributed to the paramagnetic
      characters (electron parity) of nanosized gold particles which are contingent
      upon their charge states. These novel observations suggest that the nanoparticle
      electronic energy structures can be varied by magnetic fields, leading to
      molecular manipulations of the nanoscale charge-transfer chemistry.

PMID- 11996565
TI  - Direct observation of the folding and unfolding of a beta-hairpin in explicit
      water through computer simulation.
AB  - The cooperative folding and unfolding of a beta-hairpin structure are observed in
      explicit water at native folding conditions through self-guided molecular
      dynamics simulation. The folded structure agrees excellently with the NMR NOE
      data. After going through a fully hydrated state, the peptide folds into a beta
      hairpin structure in a highly cooperative process. During the folding process it
      is observed that side chain interaction occurs first, while intrapeptide hydrogen
      bonds only form at the final stage. On the contrary, the unfolding process starts
      with the breaking of interstrand hydrogen bonds. Energetic analysis indicates
      that the driving force of the folding is the intrapeptide interaction, while the
      solvent interaction opposes the folding.

PMID- 11996566
TI  - Control and applications of immiscible liquids in microchannels.
AB  - Photolithography was used in combination with photocleavable self-assembled
      monolayers to pattern surface free energies inside microchannels enabling the
      control of the boundary between immiscible liquids. While aqueous solutions are
      confined to the hydrophilic pathways by surface forces alone, organic liquids are
      confined to the hydrophobic region only if the aqueous liquid first occupies the
      hydrophilic region. In this way, stable liquid boundaries between immiscible
      liquids are possible as long as the pressures are maintained below critical
      values. The maximum pressures are determined by the interfacial tension of the
      aqueous solution and organic liquid, channel depth, and advancing contact angle
      (theta;(a)). Experimental results on maximum pressures are in good agreement with
      the analytical values. The ability to confine and position the boundary between
      immiscible liquids inside microchannels leads to a broad range of applications in
      microfluidic systems, which is exemplified by fabrication of a semipermeable
      membrane in a surface-patterned channel via interfacial polymerization.

PMID- 11996567
TI  - Palladium-catalyzed multiple arylation of thiophenes.
AB  - Secondary 2-thiophenecarboxamides efficiently undergo unique triarylation
      accompanied by formal decarbamoylation under palladium catalysis. 3-Substituted
      thiophenes, especially having an electron-withdrawing group, can also be
      triarylated.

PMID- 11996568
TI  - Total synthesis of the ramoplanin A2 and ramoplanose aglycon.
AB  - A convergent total synthesis of the ramoplanin A2 and ramoplanose aglycon is
      disclosed. Three key subunits composed of residues 3-9 (heptapeptide 15),
      pentadepsipeptide 26, and pentapeptide 34 (residues 10-14) were prepared,
      sequentially coupled, and cyclized to provide the 49-membered depsipeptide core
      of the aglycon. Key to the preparation of the pentadepsipeptide 26 incorporating
      the backbone ester was the asymmetric synthesis of an orthogonally protected L
      threo-beta-hydroxyasparagine and the development of effective and near
      racemization free conditions for esterification of its hindered alcohol (EDCI,
      DMAP, 0 degrees C). The coupling sites were chosen to maximize the convergency of
      the synthesis including that of the three subunits, to prevent late stage
      racemization of carboxylate-activated phenylglycine-derived residues, and to
      enlist beta-sheet preorganization of an acyclic macrocyclization substrate for 49
      membered ring closure. As such, macrocyclization at the chosen Phe(9)-D-Orn(10)
      site may benefit from both beta-sheet preorganization as well as closure at a D
      amine terminus. Deliberate late stage incorporation of the subunit bearing the
      labile depsipeptide ester and a final stage Asn(1) side chain introduction
      provides future access to analogues of the aglycons which themselves are reported
      to be equally potent or more potent than the natural products in antimicrobial
      assays.

PMID- 11996569
TI  - Hybrid dendritic-linear polyester-ethers for in situ photopolymerization.
AB  - Novel first through fourth generation hybrid dendritic-linear copolymers,
      composed entirely of building blocks known to be biocompatible or degradable to
      natural metabolites in vivo, are described. Specifically, these copolymers are
      composed of poly(ethylene glycol), glycerol, and succinic acid and are
      synthesized using a divergent approach in high yield. A photo-cross-linkable
      derivative of this copolymer successfully seals 4.1 mm corneal lacerations. The
      mechanism of tissue repair is likely one of physical entrapment where an
      interpenetrating network (IPN) is formed between the cross-linked copolymer and
      the tissue.

PMID- 11996570
TI  - Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a cytochrome P
      450 in the final step of aflatoxin biosynthesis.
AB  - The major skeletal rearrangements (anthraquinone --> xanthone --> coumarin) that
      occur in the complex biosynthesis of aflatoxin B(1) are mediated by cytochromes P
      450. Previous experiments have suggested that two successive monooxygenase
      reactions are required to convert the xanthone O-methylsterigmatocystin (OMST) to
      aflatoxin, a process we demonstrate is mediated by a single P-450, OrdA, in
      Aspergillus parasiticus in accord with findings in A. flavus. The first oxidative
      cycle is proposed to result in the formation of 11-hydroxy O
      methylsterigmatocystin (HOMST), while the second entails aryl ring cleavage,
      demethylation, dehydration, decarboxylation, and rearrangement to give aflatoxin 
      a remarkable sequence of transformations. To test this hypothesis, HOMST has
      been synthesized by an alkylnitrilium variant of the Houben-Hoesch reaction. The
      troublesome xanthone carbonyl was protected as a butylene to allow further
      elaboration of the molecule, and then the product xanthone was restored in a
      uniquely facile peracid deprotection. Methods were devised to construct the
      sensitive dihydrobisfuran and to maintain the oxidation state of the partially
      methylated hydroquinone. Expression of ordA in a yeast membrane preparation
      enabled the intermediacy of HOMST both to be detected in the conversion of OMST
      to aflatoxin and to be established directly in the biosynthesis of the mycotoxin.
      Having secured the role of HOMST in aflatoxin formation, the mechanism of the
      second oxidative cycle of this P-450 is considered.

PMID- 11996571
TI  - Protein structure determination using long-distance constraints from double
      quantum coherence ESR: study of T4 lysozyme.
AB  - We report the use of a novel pulsed ESR technique for distance measurement, based
      on the detection of double quantum coherence (DQC), which yields high quality
      dipolar spectra, to significantly extend the range of measurable distances in
      proteins using nitroxide spin-labels. Eight T4 lysozyme (T4L) mutants, doubly
      labeled with methanethiosulfonate spin-label (MTSSL), have been studied using DQC
      ESR at 9 and 17 GHz. The distances span the range from 20 A for the 65/76 mutant
      to 47 A for the 61/135 mutant. The high quality of the dipolar spectra also
      allows the determination of the distance distributions, the width of which can be
      used to set upper and lower bounds in future computational strategy. It is also
      demonstrated that the shape of these distributions can reveal the presence of
      multiple conformations of the spin-label, an issue of critical relevance to the
      structural interpretation of the distances. The distances and distributions found
      in this study are readily rationalized in terms of the known crystal structure,
      the characteristic conformers of the nitroxide side chains, and molecular
      modeling. This study sets the stage for the use of DQC-ESR for determining the
      tertiary structure of large proteins with just a small number of long-distance
      constraints.

PMID- 11996572
TI  - Control of cytochrome C redox potential: axial ligation and protein environment
      effects.
AB  - Axial iron ligation and protein encapsulation of the heme cofactor have been
      investigated as effectors of the reduction potential (E degrees ') of cytochrome
      c through direct electrochemistry experiments. Our approach was that of
      partitioning the E degrees ' changes resulting from binding of imidazole, 2
      methyl-imidazole, ammonia, and azide to both cytochrome c and microperoxidase-11
      (MP11), into the enthalpic and entropic contributions. N-Acetylmethionine binding
      to MP11 was also investigated. These ligands replace Met80 and a water molecule
      axially coordinated to the heme iron in cytochrome c and MP11, respectively. This
      factorization was achieved through variable temperature E degrees ' measurements.
      In this way, we have found that (i) the decrease in E degrees ' of cytochrome c
      due to Met80 substitution by a nitrogen-donor ligand is almost totally enthalpic
      in origin, as a result of the stronger electron donor properties of the exogenous
      ligand which selectively stabilize the ferric state; (ii) on the contrary, the
      binding of the same ligands and N-acetylmethionine to MP11 results in an
      enthalpic stabilization of the reduced state, whereas the entropic effect
      invariably decreases E degrees ' (the former effect prevails for the methionine
      ligand and the latter for the nitrogenous ligands). A comparison of the reduction
      thermodynamics of cytochrome c and the MP11 adducts offers insight on the effect
      of changing axial heme ligation and heme insertion into the folded polypeptide
      chain. Principally, we have found that the overall E degrees ' increase of
      approximately 400 mV, comparing MP11 and native cytochrome c, consists of two
      opposite enthalpic and entropic terms of approximately +680 and -280 mV,
      respectively. The enthalpic term includes contributions from both axial
      methionine binding (+300 mV) and protein encapsulation of the heme (+380 mV),
      whereas the entropic term is almost entirely manifest at the stage of axial
      ligand binding. Both terms are dominated by the effects of water exclusion from
      the heme environment.

PMID- 11996573
TI  - Discrimination between peptide 3(10)- and alpha-helices. Theoretical analysis of
      the impact of alpha-methyl substitution on experimental spectra.
AB  - Detailed spectral simulations based on ab initio density functional theory
      computations of the amide I and II infrared (IR) and vibrational circular
      dichroism (VCD) spectra for Ac-(Ala)(4)-NH(2), Ac-(Aib-Ala)(2)-NH(2), and Ac
      (Aib)(4)-NH(2) constrained to 3(10)- and alpha-helical conformations are
      presented. Parameters from these ab initio calculations are transferred onto
      corresponding larger oligopeptides to simulate the spectra for dodecamers. The
      differences between conformations and for different Aib substitution patterns
      within a conformation are reflected in observable spectral patterns where data
      are available. Simulated IR spectra show small frequency shifts in the amide I
      maxima between 3(10)- and alpha-helices, but the same magnitude shifts occur
      within one conformation upon Aib substitution. Thus, from a computational basis,
      the frequency of the amide I maximum does not discriminate between the 3(10)- or
      alpha-helical conformations. Calculated VCD band shapes for 3(10)-helices showed
      more significant changes in amplitude, with change in the fraction of Aib, than
      those for alpha-helices. Generally, with increasing Aib content, the overall
      amide I VCD intensity becomes weaker and the amide I couplet becomes more
      conservative, while the amide II VCD is less affected. Although the detailed band
      shape is shown to be sensitive to alpha-Me substitution, the basic pattern of
      amide I and II relative VCD intensities still differs between alpha- and 3(10)
      helices and, as a consequence, successfully discriminates between them. These
      predictions are all borne out in experimental spectra of Aib, mixed Aib-Ala, and
      Ala-based helical peptides, where available.

PMID- 11996574
TI  - An ultrahigh resolution structure of TEM-1 beta-lactamase suggests a role for
      Glu166 as the general base in acylation.
AB  - Although TEM-1 beta-lactamase is among the best studied enzymes, its acylation
      mechanism remains controversial. To investigate this problem, the structure of
      TEM-1 in complex with an acylation transition-state analogue was determined at
      ultrahigh resolution (0.85 A) by X-ray crystallography. The quality of the data
      was such as to allow for refinement to an R-factor of 9.1% and an R(free) of
      11.2%. In the resulting structure, the electron density features were clear
      enough to differentiate between single and double bonds in carboxylate groups, to
      identify multiple conformations that are occupied by residues and loops, and to
      assign 70% of the protons in the protein. Unexpectedly, even at pH 8.0 where the
      protein was crystallized, the active site residue Glu166 is clearly protonated.
      This supports the hypothesis that Glu166 is the general base in the acylation
      half of the reaction cycle. This structure suggests that Glu166 acts through the
      catalytic water to activate Ser70 for nucleophilic attack on the beta-lactam ring
      of the substrate. The hydrolytic mechanism of class A beta-lactamases, such as
      TEM-1, appears to be symmetrical, as are the serine proteases. Apart from its
      mechanistic implications, this atomic resolution structure affords an unusually
      detailed view of the structure, dynamics, and hydrogen-bonding networks of TEM-1,
      which may be useful for the design of inhibitors against this key antibiotic
      resistance target.

PMID- 11996575
TI  - Catalytic asymmetric dihydroxylation of olefins with reusable OsO(4)(2-) on ion
      exchangers: the scope and reactivity using various cooxidants.
AB  - Exchanger-OsO(4) catalysts are prepared by an ion-exchange technique using
      layered double hydroxides and quaternary ammonium salts covalently bound to resin
      and silica as ion-exchangers. The ion-exchangers with different characteristics
      and opposite ion selectivities are specially chosen to produce the best
      heterogeneous catalyst that can operate using the various cooxidants in the
      asymmetric dihydroxylation reaction. LDH-OsO(4) catalysts composed of different
      compositions are evaluated for the asymmetric dihydroxylation of trans-stilbene.
      Resin-OsO(4) and SiO(2)-OsO(4) designed to overcome the problems associated with
      LDH-OsO(4) indeed show consistent activity and enantioselectivity in asymmetric
      dihydroxylation of olefins using K(3)Fe(CN)(6) and molecular oxygen as
      cooxidants. Compared to the Kobayashi heterogeneous systems, resin-OsO(4) is a
      very efficient catalyst for the dihydroxylation of a wide variety of aromatic,
      aliphatic, acyclic, cyclic, mono-, di-, and trisubstituted olefins to afford
      chiral vicinal diols with high yields and enantioselectivities irrespective of
      the cooxidant used. Resin-OsO(4) is recovered quantitatively by a simple
      filtration and reused for a number of cycles with consistent activity. The high
      binding ability of the heterogeneous osmium catalyst enables the use of an
      equimolar ratio of ligand to osmium to give excellent enantioselectives in
      asymmetric dihydroxylation in contrast to the homogeneous osmium system in which
      excess molar quantities of the expensive chiral ligand to osmium are invariably
      used. The complexation of the chiral ligand (DHQD)(2)PHAL, having very large
      dimension, a prerequisite to obtain higher ee, is possible only with the OsO(4)(2
      ) located on the surface of the supports.

PMID- 11996576
TI  - m-Diethynylbenzene macrocycles: syntheses and self-association behavior in
      solution.
AB  - m-Diethynylbenzene macrocycles (DBMs), buta-1,3-diyne-bridged
      [4(n)]metacyclophanes, have been synthesized and their self-association behaviors
      in solution were investigated. Cyclic tetramers, hexamers, and octamers of DBMs
      having exo-annular octyl, hexadecyl, and 3,6,9-trioxadecyl ester groups were
      prepared by intermolecular oxidative coupling of dimer units or intramolecular
      cyclization of the corresponding open-chain oligomers. The aggregation properties
      were investigated by two methods, the (1)H NMR spectra and the vapor pressure
      osmometry (VPO). Although some discrepancies were observed between the
      association constants obtained from the two methods, the qualitative view was
      consistent with each other. The analysis of self-aggregation by VPO revealed
      unique aggregation behavior of DBMs in acetone and toluene, which was not
      elucidated by the NMR method. Namely, the association constants for infinite
      association are several times larger than the dimerization constant, suggesting
      that the aggregation is enhanced by the formation of dimers (a nucleation
      mechanism). In polar solvents, DBMs aggregate more strongly than in chloroform
      due to the solvophobic interactions between the macrocyclic framework and the
      solvents. Moreover, DBMs self-associate in aromatic solvents such as toluene and
      o-xylene more readily than in chloroform. In particular, the hexameric DBM having
      a large macrocyclic cavity exhibits extremely large association constants in
      aromatic solvents. By comparing the aggregation properties of DBMs with the
      corresponding acyclic oligomers, the effect of the macrocyclic structure on the
      aggregation propensity was clarified. Finally, it turned out that DBMs tend to
      aggregate more readily than the corresponding phenylacetylene macrocycles,
      acetylene-bridged [2(n)]metacyclophanes, owing to the withdrawal of the electron
      density from the aromatic rings by the butadiyne linkages which facilitates pi-pi
      stacking interactions.

PMID- 11996577
TI  - Asymmetric carbon-carbon coupling of phenols or anilines with aryllead
      triacetates.
AB  - The asymmetric coupling of various phenol or aniline derivatives with bulky
      aryllead triacetates was thoroughly investigated using optically active amines,
      including strychnine and brucine. We found that conformationally restricted
      tertiary amines, as well as lithium aryloxides and molecular sieves, are
      essential for accelerating the rate of phenol coupling. Consequently, the
      reaction can be carried out at a low temperature (-40 to -20 degrees C) and gives
      a high degree of diastereo- and enantioselectivity. In contrast to the
      effectiveness of lithiation in phenol coupling, magnesation of anilines was a
      critical technique for aniline coupling with aryllead triacetates. Using these
      coupling methods, a diverse set of di-, tri, and polyaryl compounds with axial
      chirality can be easily obtained, and these should be useful for the construction
      of a variety of aryl-aryl frameworks involved in metal ligands, natural products,
      and artificial helical polymers.

PMID- 11996578
TI  - Tuning and dissecting electronic and steric effects in ammonium receptors:
      nonactin vs artificial receptors.
AB  - Ion selective electrodes (ISE) based on three different tripodal receptors (5, 6,
      and 7) have been investigated for sensing ammonium ion. Each receptor is based on
      three pyrazole groups that can accept three H-bonds from the bound ammonium ion.
      The receptor based on 4-bromo-3,5-dimethylpyrazole (6) is the most sensitive with
      a detection limit for ammonium ion of 2.5 x 10(-5) M at pH 8. The detection
      limits for the receptors based on 2,3-dimethylpyrazole (5) and unsubstitued
      pyrazole (7) are 1.0 x 10(-4) and 2.0 x 10(-4) M, respectively. The selectivities
      of the receptors 5, 6, and 7 for sensing ammonium ion over potassium ion
      (logK(NH)4+(/K)+) are -2.8, -2.3, and -1.7, respectively. In contrast, the
      detection limit and the selectivity of a nonactin-based ISE are 2.2 x 10(-5) M
      and -1.3, respectively. Crystallographic studies reveal that 6 accepts three H
      bonds from the bound ammonium and singly protonated receptor 5 forms three H
      bonds with the bound water molecule.

PMID- 11996580
TI  - Laser flash photolysis kinetic studies of enol ether radical cations. Rate
      constants for heterolysis of alpha-methoxy-beta-phosphatoxyalkyl radicals and for
      cyclizations of enol ether radical cations.
AB  - Two series of enol ether radical cations were studied by laser flash photolysis
      methods. The radical cations were produced by heterolyses of the phosphate groups
      from the corresponding alpha-methoxy-beta-diethylphosphatoxy or beta
      diphenylphosphatoxy radicals that were produced by 355 nm photolysis of N
      hydroxypryidine-2-thione (PTOC) ester radical precursors. Syntheses of the
      radical precursors are described. Cyclizations of enol ether radical cations 1
      gave distonic radical cations containing the diphenylalkyl radical, whereas
      cyclizations of enol ether radical cations 2 gave distonic radical cation
      products containing a diphenylcyclopropylcarbinyl radical moiety that rapidly
      ring-opened to a diphenylalkyl radical product. For 5-exo cyclizations, the
      heterolysis reactions were rate limiting, whereas for 6-exo and 7-exo
      cyclizations, the heterolyses were fast and the cyclizations were rate limiting.
      Rate constants were measured in acetonitrile and in acetonitrile solutions
      containing 2,2,2-trifluoroethanol, and several Arrhenius functions were
      determined. The heterolysis reactions showed a strong solvent polarity effect,
      whereas the cyclization reactions that gave distonic radical cation products did
      not. Recombination reactions or deprotonations of the radical cation within the
      first-formed ion pair compete with diffusive escape of the ions, and the yields
      of distonic radical cation products were a function of solvent polarity and
      increased in more polar solvent mixtures. The 5-exo cyclizations were fast enough
      to compete efficiently with other reactions within the ion pair (k approximately
      2 x 10(9) s(-1) at 20 degrees C). The 6-exo cyclization reactions of the enol
      ether radical cations are 100 times faster (radical cations 1) and 10 000 times
      faster (radical cations 2) than cyclizations of the corresponding radicals (k
      approximately 4 x 10(7) s(-1) at 20 degrees C). Second-order rate constants were
      determined for reactions of one enol ether radical cation with water and with
      methanol; the rate constants at ambient temperature are 1.1 x 10(6) and 1.4 x
      10(6) M(-1) s(-1), respectively.

PMID- 11996579
TI  - Development of an enantioselective synthetic route to neocarzinostatin
      chromophore and its use for multiple radioisotopic incorporation.
AB  - A convergent, enantioselective synthetic route to the natural product
      neocarzinostatin chromophore (1) is described. Synthesis of the chromophore
      aglycon (2) was targeted initially. Chemistry previously developed for the
      synthesis of a neocarzinostatin core model (4) failed in the requisite 1,3
      transposition of an allylic silyl ether when applied toward the preparation of 2
      with use of the more highly oxygenated substrates 27 and 54. An alternative
      synthetic plan was therefore developed, based upon a proposed reduction of the
      epoxy alcohol 58 to form the aglycon 2, a transformation that was achieved in a
      novel manner, using a combination of the reagents triphenylphosphine, iodine, and
      imidazole. The successful route to 1 and 2 began with the convergent coupling of
      the epoxydiyne 15, obtained in 9 steps (43% overall yield) from D-glyceraldehyde
      acetonide, and the cyclopentenone (+)-14, prepared in one step (75-85% yield)
      from the prostaglandin intermediate (+)-16, affording the alcohol 22 in 80% yield
      and with > or =20:1 diastereoselectivity. The alcohol 22 was then converted into
      the epoxy alcohol 58 in 17 steps with an average yield of 92% and an overall
      yield of 22%. Key features of this sequence include the diastereoselective
      Sharpless asymmetric epoxidation of allylic alcohol 81 (98% yield);
      intramolecular acetylide addition within the epoxy aldehyde 82, using Masamune's
      lithium diphenyltetramethyldisilazide base (85% yield); selective esterification
      of the diol 84 with the naphthoic acid 13 followed by selective cleavage of the
      chloroacetate protective group in situ to furnish the naphthoic acid ester 85 in
      80% yield; and elimination of the tertiary hydroxyl group within intermediate 88
      using the Martin sulfurane reagent (79% yield). Reductive transposition of the
      product epoxy alcohol (58) then formed neocarzinostatin chromophore aglycon (2,
      71% yield). Studies directed toward the glycosylation of 2 focused initially on
      the preparation of the N-methylamino --> hydroxyl replacement analogue 3, an
      alpha-D-fucose derivative of neocarzinostatin chromophore, formed in 42% yield by
      a two-step Schmidt glycosylation-deprotection sequence. For the synthesis of 1,
      an extensive search for a suitable 2'-N-methylfucosamine glycosyl donor led to
      the discovery that the reaction of 2 with the trichloroacetimidate 108,
      containing a free N-methylamino group, formed the alpha-glycoside 114 selectively
      in the presence of boron trifluoride diethyl etherate. Subsequent deprotection of
      114 under mildly acidic conditions then furnished the labile chromophore (1). The
      synthetic route was readily modified for the preparation of singly and doubly
      (3)H- and (14)C-labeled 1, compounds unavailable by other means, for studies of
      the mechanism of action of neocarzinostatin in vivo.

PMID- 11996581
TI  - Synthesis and chemistry of zwitterionic tantala-3-boratacyclopentenes: olefin
      like reactivity of a borataalkene ligand.
AB  - The compounds, where Cp' = C(5)H(5), a series, and C(5)H(4)Me, b series, are
      generated via treatment of with HB(C(6)F(5))(2). When allowed to undergo
      irreversible methane loss in the presence of an excess of the sterically modest
      alkynes 2-butyne or phenylacetylene, the putative intermediates 1a and 1b are
      trapped as the tantala-3-boratacyclopentene compounds 2 and 3, respectively. In
      these complexes, the alkyne and borataalkene ligands have reductively coupled at
      the d(2) tantalum center. For the unsymmetrical alkyne, a kinetic product
      resulting from coupling in the opposite regiochemical sense is observed; the
      thermodynamic products 3-t incorporate the phenyl group in the alpha position of
      the tantalaboratacyclic ring. Two of these compounds (2b and 3b-t) were
      characterized crystallographically. For bulkier alkynes (diphenylacetylene, 1
      phenyl-1-propyne, and 3-hexyne), intermediates with similar spectroscopic
      properties to the tantala-3-boratacyclopentenes were observed, but the ultimate
      products were the vinylalkylidene compounds 5-(R,R'). Compound 5-(Ph,Me) was
      characterized crystallographically, and it was found that the vinylalkylidene
      binds to the metal in an eta(1)-bonding mode, with the tantalum center receiving
      further ligation through a hydridoborate moiety. Mechanistic studies suggest that
      these products arise via retrocyclization of the tantala-3-boratacyclopentenes
      formed kinetically. These studies represent the first studies concerning the
      reactivity of a borataalkene ligand at a transition metal center and show that it
      can behave in an "olefin-like" manner, despite having a more flexible array of
      bonding modes available to it than an olefin.

PMID- 11996582
TI  - Template-directed self-assembly of 10-microm-sized hexagonal plates.
AB  - This article presents a strategy for the fabrication of ordered microstructures
      using concepts of design inspired by molecular self-assembly and template
      directed synthesis. The self-assembling components are 4-microm-thick hexagonal
      metal plates having sides 10 microm in length ("hexagons"), and each template
      consists of a 4-microm-thick circular metal plate surrounding a central cavity,
      the perimeter of which is complementary in shape to the external edges of a two
      dimensional, close-packed array of hexagons. The hexagons and templates
      (collectively, "pieces") were fabricated via standard procedures and patterned
      into hydrophobic and hydrophilic regions using self-assembled monolayers (SAMs).
      Templated self-assembly occurs in water through capillary interactions between
      thin films of a nonpolar liquid adhesive coating the hydrophobic faces of the
      pieces. The hexagons tile the cavities enclosed by the templates, and the
      boundaries of the cavities determine the sizes and shapes of the assemblies.
      Curing the adhesive with ultraviolet light furnishes mechanically stable arrays
      having well-defined morphologies. By allowing control over the structures of the
      resulting aggregates, this work represents a step toward the development of
      practical methods for microfabrication based on self-assembly.

PMID- 11996583
TI  - Photochemical versus thermal skeletal inversion: viscosity-controlled
      photodenitrogenation of a bridgehead-substituted DBH-type azoalkane and thermal
      syn-to-anti housane isomerization.
AB  - Upon photochemical nitrogen extrusion, azoalkane 1b yields the diastereomeric
      housane products syn-2b (inversion) and anti-2b (retention), whose syn-to-anti
      isomerization (k(iso)) is observable already at room temperature. From the
      similar viscosity dependence of the k(inv)/k(ret) data for the photolysis of the
      azoalkane 1b and the k(iso) data for the thermolysis of the housane syn-2b, we
      conclude that these skeletal inversions are subject to frictional impediments and
      these determine the stereoselectivity.

PMID- 11996584
TI  - Solution-phase parallel synthesis of a pharmacophore library of HUN-7293
      analogues: a general chemical mutagenesis approach to defining structure-function
      properties of naturally occurring cyclic (depsi)peptides.
AB  - HUN-7293 (1), a naturally occurring cyclic heptadepsipeptide, is a potent
      inhibitor of cell adhesion molecule expression (VCAM-1, ICAM-1, E-selectin), the
      overexpression of which is characteristic of chronic inflammatory diseases.
      Representative of a general approach to defining structure-function relationships
      of such cyclic (depsi)peptides, the parallel synthesis and evaluation of a
      complete library of key HUN-7293 analogues are detailed enlisting solution-phase
      techniques and simple acid-base liquid-liquid extractions for isolation and
      purification of intermediates and final products. Significant to the design of
      the studies and unique to solution-phase techniques, the library was assembled
      superimposing a divergent synthetic strategy onto a convergent total synthesis.
      An alanine scan and N-methyl deletion of each residue of the cyclic
      heptadepsipeptide identified key sites responsible for or contributing to the
      biological properties. The simultaneous preparation of a complete set of
      individual residue analogues further simplifying the structure allowed an
      assessment of each structural feature of 1, providing a detailed account of the
      structure-function relationships in a single study. Within this pharmacophore
      library prepared by systematic chemical mutagenesis of the natural product
      structure, simplified analogues possessing comparable potency and, in some
      instances, improved selectivity were identified. One potent member of this
      library proved to be an additional natural product in its own right, which we
      have come to refer to as HUN-7293B (8), being isolated from the microbial strain
      F/94-499709.

PMID- 11996585
TI  - Syntheses, structures, and surface aromaticity of the new carbaalane
      [(AlH)(6)(AlNMe(3))(2)(CCH(2)R)(6)] (R = Ph, CH(2)SiMe(3)) and a stepwise
      functionalization of the inner and outer sphere of the cluster.
AB  - The reaction of the acetylene RC triple bond CH (R = Ph, CH(2)SiMe(3)) with an
      excess of AlH(3).NMe(3) in boiling toluene leads to the carbaalane
      [(AlH)(6)(AlNMe(3))(2)(CCH(2)R)(6)] (R = Ph 1, CH(2)SiMe(3) 2) in good yield.
      Treatment of 2 with BCl(3) under varying conditions gives the chlorinated
      products [(AlCl)(6)(AlNMe(3))(2)(CCH(2)CH(2)SiMe(3))(6)] 3 and
      [(AlCl)(6)(AlNMe(3))(2)(CCH(2)CH(2)SiMe(2)Cl)(6)] 4, respectively. The latter
      clearly demonstrates that the cluster can be stepwise functionalized within the
      inner and outer sphere. The X-ray single-crystal structures of 1, 2, and 4 have
      been determined. All compounds have in common that the central core consists of a
      cluster having eight aluminum and six carbon atoms. The bonding properties in
      this cluster are described as a new manifestation of three-dimensional surface
      aromaticity. Each Al(4)C fragment of the cube is formed by four bonds with three
      electron pairs, thus leading to a strong delocalization of the electrons. A
      phenomenological modeling using a three-dimensional Huckel scheme with fitted
      parameters to reproduce the energies from ab initio calculations revealed that
      the orbital scheme localized at one Al(4)C fragment possesses an orbital sextet
      with a large HOMO-LUMO gap. This is in line with the criteria of aromaticity. The
      idea of aromaticity was sustained also by qualitative valence bond reasons
      enumerating the different resonance structures by means of graph theoretical
      methods.

PMID- 11996586
TI  - Pairing of propellers: dimerization of octahedral ruthenium(II) and osmium(II)
      complexes of eilatin via pi-pi stacking featuring heterochiral recognition.
AB  - Five octahedral eilatin complexes of the type [M(L-L)(2)(eilatin)](2+) (M = Ru,
      Os; L-L = bipyridyl-type ligands) were synthesized, and their dimerization via pi
      pi stacking was studied by crystallography and (1)H NMR techniques. The X-ray
      structures of these racemic complexes were solved and revealed that the eilatin
      complexes are organized as discrete dimers in which the eilatin residues of each
      complex are stacked in centrosymmetric packing. Chemical shift dependence on
      concentration in the (1)H NMR spectra support fast dimer-monomer equilibrium, and
      the structures of the dimers in acetonitrile solution are proposed to be
      analogous to their solid-state structures. Dimerization constants in acetonitrile
      were measured for the five racemic eilatin complexes that exhibit different
      structural parameters, as well as for the two enantiomeric forms of one of these
      complexes. They were found to be independent of the metal (Ru vs Os), strongly
      dependent on the steric effects introduced by the L-L ligands (2,2'-bipyridine,
      1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, and 2,2'-biquinoline), and
      dependent on the optical purity of the complexes. A clear preference for
      heterochiral over homochiral dimer formation was demonstrated. This is the first
      report of chiral recognition in solution, exhibited by simple chemical systems
      held solely by pi-stacking interactions.

PMID- 11996587
TI  - In situ EXAFS analysis of the temperature-programmed reduction of Cu-ZSM-5.
AB  - High resolution in situ EXAFS during temperature-programmed reduction was
      performed on Cu-ZSM-5 to elucidate the state of copper under reaction conditions.
      Improvements in hardware and software allowed rapid acquisition of both XANES and
      EXAFS data during reduction, in particular, allowing observation of
      characteristic preedge features from various Cu oxidation states. EXAFS fitting
      and factor analysis of the normalized XANES edge were performed in an attempt to
      determine the number and type of Cu species present. The data suggests that
      initially only Cu(2+) is present in two different locations on the zeolite; both
      states reduce to Cu(1+) in both H(2) and CO, but under different conditions.
      Under H(2) conditions, migration of Cu(1+) to Cu(0) clusters is observed at 450
      degrees C, while no metallic state is observed during CO reduction.

PMID- 11996588
TI  - Pressure-induced volume expansion of zeolites in the natrolite family.
AB  - Powder diffraction patterns of the zeolites natrolite
      (Na(16)Al(16)Si(24)O(80).16H(2)O), mesolite
      (Na(5.33)Ca(5.33)Al(16)Si(24)O(80).21.33H(2)O), scolecite
      (Ca(8)Al(16)Si(24)O(80).24H(2)O), and a gallosilicate analogue of natrolite
      (K(16)Ga(16)Si(24)O(80).12H(2)O), all crystallizing with a natrolite framework
      topology, were measured as a function of pressure up to 5.0 GPa with use of a
      diamond-anvil cell and a 200 microm focused monochromatic synchrotron X-ray beam.
      Under the hydrostatic conditions mediated by an alcohol and water mixture, all
      these materials showed an abrupt volume expansion (ca. 2.5% in natrolite) between
      0.8 and 1.5 GPa without altering the framework topology. Rietveld refinements
      using the data collected on natrolite show that the anomalous swelling is due to
      the selective sorption of water from the pressure-transmission fluid expanding
      the channels along the a- and b-unit cell axes. This gives rise to a
      "superhydrated" phase of natrolite with an approximate formula of
      Na(16)Al(16)Si(24)O(80).32H(2)O, which contains hydrogen-bonded helical water
      nanotubes along the channels. In mesolite, which at ambient pressure is composed
      of ordered layers of sodium- and calcium-containing channels in a 1:2 ratio along
      the b-axis, this anomalous swelling is accompanied by a loss of the superlattice
      reflections (b(mesolite) = 3b(natrolite)). This suggests a pressure-induced order
      disorder transition involving the motions of sodium and calcium cations either
      through cross-channel diffusion or within the respective channels. The powder
      diffraction data of scolecite, a monoclinic analogue of natrolite where all
      sodium cations are substituted by calcium and water molecules, reveal a
      reversible pressure-induced partial amorphization under hydrostatic conditions.
      Unlike the 2-dimensional swelling observed in natrolite and mesolite, the volume
      expansion of the potassium gallosilicate natrolite is 3-dimensional and includes
      the lengthening of the channel axis. In addition, the expanded phase, stable at
      high pressure, is retained at ambient conditions after pressure is released. The
      unprecedented and intriguing high-pressure crystal chemistry of zeolites with the
      natrolite framework topology is discussed here relating the different types of
      volume expansion to superhydration.

PMID- 11996589
TI  - Preparation and structure of (Cu(pc))(3)(ReO(4))(2) and theoretical investigation
      of Cu(pc)(ReO(4)), Cu(pc)(ReO(4))(2), and (Cu(pc))(3)(ReO(4))(2).
AB  - The compound (Cu(pc))(3)(ReO(4))(2) (pc = phthalocyaninato) has been prepared by
      electrocrystallization from a p-dichlorobenzene solution of Cu(pc) and [N(n
      Bu)(4)][ReO(4)]. (Cu(pc))(3)(ReO(4))(2) crystallizes with one formula unit in the
      triclinic space group P1 with cell constants at T = 153 K of a = 12.6202(6) A, b
      = 13.7596(7) A, c = 14.0294(7) A, alpha = 64.6376(9) degrees, beta = 64.2570(9)
      degrees, and gamma = 66.0549(9) degrees. The molecular structure comprises a
      stack of three Cu(pc) rings; the Cu center in each peripheral ring has an
      attached ReO(4) ligand, the Cu-O distance being 2.374(5) A. The inter-ring
      distance is 3.1595(11) A. Density functional theory calculations for
      Cu(pc)(ReO(4)) and Cu(pc)(ReO(4))(2) suggest that the ring-pi states are the
      source of the electron donation to the ligands. Calculations for
      (Cu(pc))(3)(ReO(4))(2) suggest that the charges on the central and peripheral
      rings are nearly equal. For all three compounds the basic spin distributions are
      similar to each other and to those of other Cu(pc) systems. For
      (Cu(pc))(3)(ReO(4))(2) a localized, rather than an itinerant, description of the
      magnetism is indicated.

PMID- 11996590
TI  - Mapping the cytochrome C folding landscape.
AB  - The solution to the riddle of how a protein folds is encoded in the
      conformational energy landscape for the constituent polypeptide. Employing
      fluorescence energy transfer kinetics, we have mapped the S.cerevisiae iso-1
      cytochrome c landscape by monitoring the distance between a C-terminal
      fluorophore and the heme during folding. Within 1 ms after denaturant dilution to
      native conditions, unfolded protein molecules have evolved into two distinct and
      rapidly equilibrating populations: a collection of collapsed structures with an
      average fluorophore-heme distance (r) of 27 A and a roughly equal population of
      extended polypeptides with r > 50 A. Molecules with the native fold appear on a
      time scale regulated by heme ligation events ( approximately 300 ms, pH 7). The
      experimentally derived landscape for folding has a narrow central funnel with a
      flat upper rim on which collapsed and extended polypeptides interchange rapidly
      in a search for the native structure.

PMID- 11996591
TI  - Carbon-13 NMR shielding in the twenty common amino acids: comparisons with
      experimental results in proteins.
AB  - We have used ab initio quantum chemical techniques to compute the (13)C(alpha)
      and (13)C(beta) shielding surfaces for the 14 amino acids not previously
      investigated (R. H. Havlin et al., J. Am. Chem. Soc. 1997, 119, 11951-11958) in
      their most popular conformations. The spans (Omega = sigma(33) - sigma(11)) of
      all the tensors reported here are large ( approximately 34 ppm) and there are
      only very minor differences between helical and sheet residues. This is in
      contrast to the previous report in which Val, Ile and Thr were reported to have
      large ( approximately 12 ppm) differences in Omega between helical and sheet
      geometries. Apparently, only the beta-branched (beta-disubstituted) amino acids
      have such large CSA span (Omega) differences; however, there are uniformly large
      differences in the solution-NMR-determined CSA (Deltasigma = sigma(orth) -
      sigma(par)) between helices and sheets in all amino acids considered. This effect
      is overwhelmingly due to a change in shielding tensor orientation. With the aid
      of such shielding tensor orientation information, we computed Deltasigma values
      for all of the amino acids in calmodulin/M13 and ubiquitin. For ubiquitin, we
      find only a 2.7 ppm rmsd between theory and experiment for Deltasigma over an
      approximately 45 ppm range, a 0.96 slope, and an R(2) = 0.94 value when using an
      average solution NMR structure. We also report C(beta) shielding tensor results
      for these same amino acids, which reflect the small isotropic chemical shift
      differences seen experimentally, together with similar C(beta) shielding tensor
      magnitudes and orientations. In addition, we describe the results of calculations
      of C(alpha), C(beta), C(gamma)1, C(gamma)2, and C(delta) shifts in the two
      isoleucine residues in bovine pancreatic trypsin inhibitor and the four
      isoleucines in a cytochrome c and demonstrate that the side chain chemical shifts
      are strongly influenced by chi(2) torsion angle effects. There is very good
      agreement between theory and experiment using either X-ray or average solution
      NMR structures. Overall, these results show that both C(alpha) backbone chemical
      shift anisotropy results as well as backbone and side chain (13)C isotropic
      shifts can now be predicted with good accuracy by using quantum chemical methods,
      which should facilitate solution structure determination/refinement using such
      shielding tensor surface information.

PMID- 11996592
TI  - Spectroscopic properties of tyrosyl radicals in dipeptides.
AB  - Redox-active tyrosine residues play important roles in long-distance electron
      reactions in enzymes, including prostaglandin H synthase, galactose oxidase,
      ribonucleotide reductase, and photosystem II. Magnetic resonance and vibrational
      spectroscopy provide methods with which to study the structures of redox-active
      amino acids in proteins. In this report, ultraviolet photolysis was used to
      generate tyrosyl radicals from polycrystalline tyrosinate or dipeptides, and the
      structure of the radical was investigated with EPR and reaction-induced FT-IR
      spectroscopy at 77 K. Photolysis at 77 K is expected to generate a neutral
      tyrosyl radical through oxidation of the aromatic ring. EPR and FT-IR results
      obtained from (13)C-labeled tyrosine were consistent with that expectation.
      Surprisingly, labeling of the tyrosyl amino group with (15)N also resulted in
      isotope-shifted bands in the photolysis spectrum. The force constant of a NH
      deformation mode increased when the tyrosyl radical was generated. These data
      suggest an interaction between the pi system of the tyrosyl radical and the amino
      group. In spectra acquired from the dipeptides, evidence for a sequence-dependent
      interaction between the tyrosyl radical and the amide bond of the dipeptide was
      also obtained. We postulate that perturbation of the amino or the amide/imide
      groups may occur through a spin polarization mechanism, which is indirectly
      detected as a change in NH force constant. This conclusion is supported by
      density functional calculations, which suggest a conformationally sensitive
      delocalization of spin density onto the amino and carboxylate groups of the
      tyrosyl radical. These experiments provide a step toward a detailed spectral
      interpretation for protein-based tyrosyl radicals.

PMID- 11996593
TI  - A DFT computational study of the bis-silylation reaction of acetylene catalyzed
      by palladium complexes.
AB  - In this paper we have investigated at the DFT(B3LYP) level the catalytic cycle
      for the bis-silylation reaction of alkynes promoted by palladium complexes. A
      model-system formed by an acetylene molecule, a disilane molecule, and the
      Pd(PH(3))(2) complex has been used. The most relevant features of this catalytic
      cycle can be summarized as follows: (i) The first step of the cycle is an
      oxidative addition involving H(3)Si-SiH(3) and Pd(PH(3))(2). It occurs easily and
      leads to the cis (SiH(3))(2)Pd(PH(3))(2) complex that is 5.39 kcal mol(-1) lower
      in energy than reactants. (ii) The transfer of the two silyl groups to the C-C
      triple bond does not occur in a concerted way, but involves many steps. (iii) The
      cis (SiH(3))(2)Pd(PH(3))(2) complex, obtained from the oxidative addition, is
      involved in the formation of the first C-Si bond (activation barrier of 18.34
      kcal mol(-1)). The two intermediates that form in this step cannot lead directly
      to the formation of the final bis(silyl)ethene product. However, they can
      isomerize rather easily (the two possible isomerizations have a barrier of 16.79
      and 7.17 kcal mol(-1)) to new more stable species. In both these new
      intermediates the second silyl group is adjacent to the acetylene moiety and the
      formation of the second C-Si bond can occur rapidly leading to the (Z)
      bis(silyl)ethene, as experimentally observed. (iv) The whole catalytic process is
      exothermic by 41.54 kcal mol(-1), in quite good agreement with the experimental
      estimate of this quantity (about 40 kcal mol(-1)).

PMID- 11996594
TI  - Directing power of cyclobutenoid annelations on the double bonds of planar
      cyclooctatetraenes.
AB  - Ab initio and hybrid density functional quantum mechanical computations are
      applied to the structure and energetics of a series of two-atom-bridge annelated
      cyclooctatetraenes. The contribution of each annelation to the exo/endo relative
      energy is estimated. Key directing factors for a given type of annelation, such
      as strain, electronegativity, or cyclic electron count, can be sorted out by
      comparison of various bridge compositions. Overall, electron count and the
      essential components of the Clar/Robinson rule work well to predict the exo/endo
      preferences. Specifically, three 4-e(-) Huckel systems (CH-CH, NH-BH and NH-C(O))
      display dominant exo forms whereas the three 4n + 2 Huckel counterparts (C(O)
      C(O), BH-BH, and planar NH-NH) display a common preference for endo. These endo
      systems act like four independent four-membered "aromatic" rings linked by
      "single" bonds. An analysis based on the effective hybridization of carbon atoms
      in the annulene (Bent's rule) provides a rationale for subtle trends in their
      specific annulene geometry.

PMID- 11996595
TI  - Femtosecond electron-transfer reactions in mono- and polynucleotides and in DNA.
AB  - Quenching of redox active, intercalating dyes by guanine bases in DNA can occur
      on a femtosecond time scale both in DNA and in nucleotide complexes.
      Notwithstanding the ultrafast rate coefficients, we find that a classical,
      nonadiabatic Marcus model for electron transfer explains the experimental
      observations, which allows us to estimate the electronic coupling (330 cm(-1))
      and reorganization (8070 cm(-1)) energies involved for thionine-[poly(dG-dC)](2)
      complexes. Making the simplifying assumption that other charged, pi-stacked DNA
      intercalators also have approximately these same values, the electron-transfer
      rate coefficients as a function of the driving force, DeltaG, are derived for
      similar molecules. The rate of electron transfer is found to be independent of
      the speed of molecular reorientation. Electron transfer to the thionine singlet
      excited state from DNA obtained from calf thymus, salmon testes, and the
      bacterium, micrococcus luteus (lysodeikticus) containing different fractions of G
      C pairs, has also been studied. Using a Monte Carlo model for electron transfer
      in DNA and allowing for reaction of the dye with the nearest 10 bases in the
      chain, the distance dependence scaling parameter, beta, is found to be 0.8 +/-
      0.1 A(-1). The model also predicts the redox potential for guanine dimers, and we
      find this to be close to the value for isolated guanine bases. Additionally, we
      find that the pyrimidine bases are barriers to efficient electron transfer within
      the superexchange limit, and we also infer from this model that the electrons do
      not cross between strands on the picosecond time scale; that is, the electronic
      coupling occurs predominantly through the pi-stack and is not increased
      substantially by the presence of hydrogen bonding within the duplex. We conclude
      that long-range electron transfer in DNA is not exceptionally fast as would be
      expected if DNA behaved as a "molecular wire" but nor is it as slow as is seen in
      proteins, which do not benefit from pi-stacking.

PMID- 11996596
TI  - Bond insertion, complexation, and penetration pathways of vapor-deposited
      aluminum atoms with HO- and CH(3)O-terminated organic monolayers.
AB  - The interaction of vapor-deposited Al atoms with self-assembled monolayers (SAMs)
      of HS-(CH(2))(16)-X (X = -OH and -OCH(3)) chemisorbed at polycrystalline Au[111]
      surfaces was studied using time-of-flight secondary-ion mass spectrometry, X-ray
      photoelectron spectroscopy, and infrared reflectance spectroscopy. Whereas
      quantum chemical theory calculations show that Al insertion into the C-C, C-H, C
      O, and O-H bonds is favorable energetically, it is observed that deposited Al
      inserts only with the OH SAM to form an -O-Al-H product. This reaction appears to
      cease prior to complete -OH consumption, and is followed by formation of a few
      overlayers of a nonmetallic type of phase and finally deposition of a metallic
      film. In contrast, for the OCH(3) SAM, the deposited Al atoms partition along two
      parallel paths: nucleation and growth of an overlayer metal film, and penetration
      through the OCH(3) SAM to the monolayer/Au interface region. By considering a
      previous observation that a CH(3) terminal group favors penetration as the
      dominant initial process, and using theory calculations of Al-molecule
      interaction energies, we suggest that the competition between the penetration and
      overlayer film nucleation channels is regulated by small differences in the Al
      SAM terminal group interaction energies. These results demonstrate the highly
      subtle effects of surface structure and composition on the nucleation and growth
      of metal films on organic surfaces and point to a new perspective on
      organometallic and metal-solvent interactions.

PMID- 11996597
TI  - Strong electronic consequences of intercalation in cuprate superconductors: the
      case of a trigonal planar AuI(3) complex stabilized in the Bi(2)Sr(2)CaCu(2)O(y)
      lattice.
AB  - Recently, a molecular AuI(3) complex was stabilized in the interlayer space of
      the Bi(2)Sr(2)CaCu(2)O(y) (Bi2212) high-T(c) superconducting phase, adopting an
      exceptional D(3)(h) structure (Choy, J.-H.; et al. J. Phys.Chem. B 2000, 104,
      7273). If the gold were formally Au(III), a strong Jahn-Teller distortion to T-
      and Y-shaped structures would be expected. In this work, we try to understand the
      structural preferences of AuI(3) in both the gas phase and the Bi2212 lattice, as
      well as the influence of the AuI(3) intercalation on the superconductor lattice.
      What we think actually happens is that there is an effective electron transfer
      from the s-type Bi lone pair to the gold, increasing the formal oxidation state
      of Bi from +3 to +5 and decreasing that of Au from +3 to +1. A trigonal Au(I)
      trihalide is just fine. The DFT results confirm in the Bi-rich regions the same
      kind of electron transfer as encountered on the EHT level of theory, but they
      reveal additional complexities of the problem. The effect of the Bi to
      intercalating molecule electron transfer on the cuprate layer may be important,
      quite apart from this specific example, in tuning superconductivity in the
      cuprates.

PMID- 11996598
TI  - Charge transport through self-assembled monolayers of compounds of interest in
      molecular electronics.
AB  - The electrical properties of self-assembled monolayers (SAMs) on metal surfaces
      have been explored for a series of molecules to address the relation between the
      behavior of a molecule and its structure. We probed interfacial electron transfer
      processes, particularly those involving unoccupied states, of SAMs of thiolates
      or arylates on Au by using shear force-based scanning probe microscopy (SPM)
      combined with current-voltage (i-V) and current-distance (i-d) measurements. The
      i-V curves of hexadecanethiol in the low bias regime were symmetric around 0 V
      and the current increased exponentially with V at high bias voltage. Different
      than hexadecanethiol, reversible peak-shaped i-V characteristics were obtained
      for most of the nitro-based oligo(phenylene ethynylene) SAMs studied here,
      indicating that part of the conduction mechanism of these junctions involved
      resonance tunneling. These reversible peaked i-V curves, often described as a
      negative differential resistance (NDR) effect of the junction, can be used to
      define a threshold tip bias, V(TH), for resonant conduction. We also found that
      for all of the SAMs studied here, the current decreased with increasing distance,
      d, between tip and substrate. The attenuation factor beta of hexadecanethiol was
      high, ranging from 1.3 to 1.4 A(-1), and was nearly independent of the tip bias.
      The beta-values for nitro-based molecules were low and depended strongly on the
      tip bias, ranging from 0.15 A(-1) for tetranitro oligo(phenylene ethynylene)
      thiol, VII, to 0.50 A(-1) for dinitro oligo(phenylene) thiol, VI, at a -3.0 V tip
      bias. Both the V(TH) and beta values of these nitro-based SAMs were also strongly
      dependent on the structures of the molecules, e.g. the number of electroactive
      substituent groups on the central benzene, the molecular wire backbone, the
      anchoring linkage, and the headgroup. We also observed charge storage on nitro
      based molecules. For a SAM of the dintro compound, V, approximately 25% of charge
      collected in the negative scan is stored in the molecules and can be collected at
      positive voltages. A possible mechanism involving lateral electron hopping is
      proposed to explain this phenomenon.

PMID- 11996599
TI  - A prototype for catalyzed amide bond cleavage: production of the [NH(3),
      H(2)O](*)(+) dimer from ionized formamide and its carbene isomer.
AB  - The reaction of ionized formamide H(2)NCHO(*)(+) with water leads to an exclusive
      loss of CO from the complex. This contrasts with the unimolecular reaction of low
      energy ionized formamide, which loses exclusively one hydrogen atom. The
      unimolecular loss of CO is not observed because it involves several H-transfers
      corresponding to high-energy barriers. Experimental and theoretical studies of
      the role of solvation by water on the fragmentation of ionized formamide leads to
      three different results: (i) In contrast with different systems previously
      studied, in which solvation plays only a role on one or two steps of a reaction,
      a molecule of water is efficient in the catalysis of the decarbonylation process
      because water catalyzes all the steps of the reaction of ionized formamide,
      including the final dissociation of the amide bond. (ii) The catalyzed
      isomerization of carbonylic radical cations into their carbene counterparts is
      shown to be an important step in the process. To study this step, a precise
      probe, characterizing the carbene structure by ion-molecule reaction, is for the
      first time described. (iii) Finally, decarbonylation of ionized formamide yields
      the [NH(3), H(2)O](*)(+) ion, which has not been generated and experimentally
      studied previously. By this method, the [NH(3), H(2)O](*)(+) ion is generated in
      abundance and with a low internal energy content, allowing one either to prepare,
      by ligand exchange, a series of other solvated radical cations or to generate
      covalent structures such as distonic ions. First results on related systems
      indicate that the conclusions obtained for ionized formamide are widespread.

PMID- 11996600
TI  - Close-packed C(70)(3-) phases - synthesis, structure, and electronic properties.
AB  - The high symmetry and resulting electronic degeneracy of the C(60)(3)(-) anion is
      viewed as the key molecular feature in the high superconducting transition
      temperatures of fulleride and oxidized fullerene systems. The experimental
      evaluation of this hypothesis requires the synthesis of face-centered cubic (fcc)
      trivalent fulleride anion salts derived from higher fullerenes such as C(70),
      which have thus far proved elusive with only stable A(1)C(70), A(4)C(70), and
      A(6)C(70) phases known. In this paper, we report the synthesis of fcc A(3)C(70)
      phases stabilized by size-matching the tetrahedral site with the sodium cation.
      The structures are strongly dependent on the cooling protocol due to the
      existence of metastable partially or completely orientationally disordered
      phases. EPR data indicate that the phases are metallic but not superconducting.
      The densities of states at the Fermi level appear too low to give
      superconductivity at above 5 K, consistent with recent observations that four
      electrons per C(70) anion are required for superconductivity. Size-matching on
      both the octahedral and tetrahedral sites is required for A(3)C(70) stability -
      K(2)CsC(70) is only stable at elevated temperature and Na(2)C(70) is unstable,
      the composition corresponding to C(70) and a sodium-rich trigonal phase.

PMID- 11996601
TI  - Paramagnetically induced residual dipolar couplings for solution structure
      determination of lanthanide binding proteins.
AB  - Lanthanides may substitute calcium in calcium-binding proteins, such as, for
      instance, EF-hand proteins. Paramagnetic lanthanides are capable of orienting the
      protein in high magnetic fields to an extent similar to that obtained by using
      orienting devices, and each lanthanide orients according to its magnetic
      susceptibility tensor. Here, Ce(3+), Tb(3+), Dy(3+), Ho(3+), Er(3+), Tm(3+),
      Yb(3+) in the C-terminal site of calbindin D(9k) have been investigated. Such
      systems provide (1)H-(15)N residual dipolar couplings (rdc) which can be used for
      solution structure determinations. Within the frame of optimizing the use of
      residual dipolar couplings for efficient solution structure determination, it is
      proposed here to use a number of lanthanides (e.g., >2) to obtain the
      orientations of the internuclear vectors with respect to an arbitrary reference
      system. This is facilitated by the independent knowledge of the magnetic
      susceptibility anisotropy tensor of each metal, obtained from the analysis of the
      pseudocontact shifts. A further module of the program PARAMAGNETIC-DYANA, called
      RDCDYANA-ANGLES, is developed to efficiently incorporate such rdc-derived
      orientations, instead of the rdc themselves, as constraints in the solution
      structure calculation. This strategy is absolutely general and can be extended to
      any other pair of dipole-dipole coupled nuclei. The effect of mobility is also
      assessed. In principle, information on the mobility can be obtained with a number
      of lanthanide ions >5, or by combining a smaller number of lanthanide ions with a
      few orienting devices.

PMID- 11996602
TI  - High-pressure (1 Torr) scanning tunneling microscopy (STM) study of the
      coadsorption and exchange of CO and NO on the Rh(111) crystal face.
AB  - The coadsorption of CO and NO on Rh(111) at room temperature was studied with
      scanning tunneling microscopy (STM) in the catalytically relevant range of
      approximately 1 Torr. For gas mixtures where NO is not in large excess, a mixed
      layer with (2x2) structure is formed. The difference in binding energy between CO
      and NO on top sites was determined from the measured surface (by direct counting
      in STM images) and gas mole fractions of each species. A model for the molecular
      structure is proposed based on the analysis of exchange events between CO and NO
      molecules in the images. In this model as the partial pressure of NO increases,
      NO molecules occupy hollow sites first, by displacing CO, and top sites later,
      where they coexist with CO. As the surface fraction of NO increases, favorable NO
      NO interactions cause the formation of segregated NO-rich regions. As with pure
      NO, a phase transition from the (2x2)-NO to the (3x3)-NO structure takes place in
      the NO-rich regions at high NO concentration. These results demonstrate the
      unique ability of STM to obtain molecular-level information under catalytic
      pressure conditions.

PMID- 11996603
TI  - Generalized principle of designing neutral superstrong Bronsted acids.
AB  - A generalized principle of designing superstrong Bronsted acids is suggested
      according to the following scheme: M=O --> M=Z(X)(n). It consists of the formal
      replacement of =O fragment in carbonyl, sulfonyl, etc. groups in various acidic
      systems (e.g., CH(3)CHO, FSO(3)H, where M is the CH(3)CH= or FSO(2)H=fragment,
      respectively) by =NSO(2)F, =NCN, =C(CN)(2), =P(SO(2)F)(3), =S(CN)(4), or any
      other formally bivalent group =Z(X)(n) (where the formal valency of the central
      atom Z is n + 2), leading to highly acidic systems (e.g., HC(=P(CN)(3))NH(2),
      FS(=C(CN)(2))(2)OH, etc.). It is demonstrated that in several cases the
      introduction of the double-bonded substituent at the central atom (e.g., N, C, P,
      S, Cl) that carries the potentially acidic proton or the acidity site (e.g., OH,
      NH(2), CH(3), etc. groups) will lead to the enormous (up to ca. 120 kcal/mol or
      88 pK(a) units!) increase of the intrinsic acidity of the respective parent acid.
      The acidity of the resulting acids and the scope and limitations of the principle
      are explored using density functional theory calculations at B3LYP 6-311+G level.
      Some of the resulting acids (or their anions) were found to undergo fragmentation
      in the course of the geometry optimization. The general trend that follows from
      the results of the calculations is that the stability of the resulting compounds
      is influenced by both the M and the Z. If M is a first row element (carbon or
      nitrogen), then stable species are produced with almost any Z. If M is a second
      row element (sulfur or phosphorus), then the species with first row Z are mostly
      predicted to be stable, but most of the species with second row Z are expected to
      undergo fragmentation during the geometry optimization. The Z = N and Z = C
      derivatives (e.g., =NSO(2)CF(3), =C(CN)(2), =C(SO(2)CF(3))(2), etc.) are
      predicted to be the most stable. However, they have relatively modest electron
      accepting power as compared to their penta-, hexa-, and heptavalent counterparts.
      The acidifying effects of the =Z(X)(n)() groups with the same X increase with
      increasing n: =NCN < =C(CN)(2) < =P(CN)(3) < =S(CN)(4) and =NSO(2)F <
      =C(SO(2)F)(2) < =P(SO(2)F)(3). Also, the acidifying effect of a fluorosulfonyl
      substituted substituent is higher than that of the corresponding cyano
      substituted substituent.

PMID- 11996604
TI  - National health insurance: liberal benefits, conservative spending.

PMID- 11996605
TI  - "What should I do, doc?": Some psychologic benefits of physician recommendations.

PMID- 11996606
TI  - Forgetting, fabricating, and telescoping: the instability of the medical history.
AB  - Patients' recollections of their past symptoms, illnesses, and episodes of care
      are often inconsistent from one inquiry to the next. Patients frequently fail to
      recall (and therefore underreport) the incidence of previous symptoms and events;
      tend to combine separate, similar occurrences into a single, generic memory; and
      falsely recall medical events and symptoms that did not in fact occur. This
      unreliability of recall is affected by personality characteristics and by the
      patient's current state at the time of recall. Thus, current anxiety or
      depression and pain or bodily distress foster the recall of symptoms and events
      that are not recalled when the patient is more comfortable. Finally, current
      beliefs about one's health and the nature and causes of one's illness also affect
      the recall of past symptoms and illness. Physicians can maximize the reliability
      of the clinical history by (1) noting and taking into account the patient's
      current physical and emotional state; (2) first establishing historical "anchor
      points" or memorable milestones; (3) decomposing generic memories by finding
      features that distinguish them from each other; and (4) recalling the clinical
      history in retrograde fashion, beginning with the most recent event and working
      backward.

PMID- 11996607
TI  - Rifampin and rifabutin drug interactions: an update.
AB  - Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. A few
      examples of well-documented clinically significant interactions include
      interactions with warfarin, oral contraceptives, cyclosporine, glucocorticoids,
      ketoconazole or itraconazole, theophylline, quinidine sulfate, digitoxin or
      digoxin, verapamil hydrochloride, human immunodeficiency virus-related protease
      inhibitors, zidovudine, delavirdine mesylate, nifedipine, and midazolam. Recent
      reports have demonstrated clinically relevant interactions with numerous other
      drugs, such as buspirone hydrochloride, zolpidem tartrate, simvastatin,
      propafenone hydrochloride, tacrolimus, ondansetron hydrochloride, and opiates.
      Rifabutin reduces serum concentrations of antiretroviral agents, but less so than
      rifampin. To avoid a reduced therapeutic response, therapeutic failure, or toxic
      reactions when rifampin is added to or discontinued from medication regimens,
      clinicians need to be cognizant of these interactions. Enhanced knowledge of
      known interactions will continue to develop, including research on the induction
      of specific cytochrome P-450 isoenzymes and on the importance of the P
      glycoprotein transport system. New rifampin and rifabutin interactions will be
      discovered with further investigations.

PMID- 11996608
TI  - Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular
      disease: the bezafibrate infarction prevention registry.
AB  - BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl
      coenzyme A reductase inhibitors reduce the incidence of stroke in patients with
      coronary heart disease (CHD), the associations between blood lipid levels and
      cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood
      cholesterol level and its fractions are risk factors for stroke in a large group
      of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD
      who were screened for but not included in the Bezafibrate Infarction Prevention
      study, a secondary prevention randomized clinical trial of lipid modification,
      and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up
      period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487
      had verified ischemic stroke or transient ischemic attack (TIA). RESULTS:
      Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic
      stroke or TIA were identified with increasing cholesterol and low-density
      lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol
      levels, and decreasing percentage of total serum cholesterol contained in the HDL
      moiety. In logistic regression models, adjusting for clinical covariates, the
      following odds ratios (95% confidence intervals) were identified for lipid values
      in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total
      cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27
      1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of
      serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for
      the end point of verified ischemic stroke or TIA. CONCLUSION: These findings
      clearly support the role of total cholesterol and its fractions in prediction of
      ischemic CVD among patients with established CHD.

PMID- 11996609
TI  - Epidemiological evidence of increased bone mineral density in habitual tea
      drinkers.
AB  - BACKGROUND: Researchers have hypothesized that bone mineral density (BMD) may be
      influenced by chemical compounds such as caffeine, phytoestrogen, fluoride, and
      many compounds that are contained in tea extracts. Hence, the relationship
      between habitual tea consumption and BMD is an interesting issue. METHODS: Based
      on an epidemiological survey, we enrolled 497 men and 540 women, 30 years and
      older, in our study. All subjects were questioned about their habit of tea
      consumption and other lifestyle characteristics by means of a structured
      questionnaire. Dual-energy x-ray absorptiometry was used to measure the BMD of
      the total body, lumbar spine (L1-L4), hip neck, and Ward triangle regions.
      RESULTS: Five hundred two subjects (48.4%) were habitual tea drinkers, with a
      mean duration of tea consumption of approximately 10 years. Compared with
      nonhabitual tea drinkers, subjects with habitual tea consumption of 6 to 10 years
      showed higher lumbar spine BMDs, and those with consumption of more than 10 years
      showed the highest BMDs of all measured regions. Under the multiple stepwise
      regression models, sex, age, body mass index, total physical activity, and habit
      of tea consumption were the major significant variables for the different BMD
      regions. Regarding the behavioral characteristics of tea consumption, the
      duration of tea consumption was the only independent determinant for the BMDs.
      CONCLUSION: Habitual tea consumption, especially for more than 10 years, has
      significant beneficial effects on BMD of the total body, lumbar spine, and hip
      regions in adults.

PMID- 11996610
TI  - Serum potassium and risk of cardiovascular disease: the Framingham heart study.
AB  - BACKGROUND: Published studies of the association between serum potassium
      concentration and risk for cardiovascular disease in community-based populations
      have reported conflicting results. We sought to determine the association between
      serum potassium concentration and cardiovascular disease risk in the Framingham
      Heart Study. METHODS: A total of 3151 participants (mean age, 43 years; 48% men)
      in the Framingham Heart Study who were free of cardiovascular disease and not
      taking medications affecting potassium homeostasis had serum potassium levels
      measured (1979-1983). Proportional hazards models were used to determine the
      association of serum potassium concentration at baseline with the incidence of
      cardiovascular disease at follow-up. RESULTS: During mean follow-up of 16 years,
      313 cardiovascular disease events occurred, including 46 cardiovascular disease
      related deaths. After adjustment for age, serum potassium level was marginally
      associated with risk of cardiovascular disease (hazard ratio [HR] per 1 mg/dL
      increment, 1.03; 95% confidence interval [CI], 1.00-1.05; P =.02). However, after
      further adjustment for multiple confounders, serum potassium level was not
      significantly associated with cardiovascular disease risk (HR, 1.00; 95% CI, 0.98
      1.03). There were no significant associations between serum potassium level and
      cardiovascular disease-related death in either age- and sex-adjusted models (HR,
      1.06; 95% CI, 0.99-1.12) or multivariable-adjusted models (HR, 1.04; 95% CI, 0.97
      1.11). CONCLUSION: In our community-based sample of individuals free of
      cardiovascular disease and not taking medications that affect potassium
      homeostasis, serum potassium level was not associated with risk of cardiovascular
      disease.

PMID- 11996611
TI  - Use of cholesterol-lowering therapy by elderly adults after myocardial
      infarction.
AB  - BACKGROUND: Use of cholesterol-lowering drugs reduces mortality and adverse
      cardiac events among people aged 65 to 75 years with coronary heart disease, but
      previous studies have shown that most patients have not received this treatment.
      METHODS: We conducted a telephone survey during 1999 and 2000 of 815 Medicare
      beneficiaries aged 65 to 74 years hospitalized for an acute myocardial infarction
      in California, Florida, Massachusetts, New York, or Pennsylvania during 1994 and
      1995. Outcome measures included use of cholesterol-lowering drugs, beliefs about
      the importance of lowering cholesterol levels, and knowledge of personal
      cholesterol levels, adjusting for demographic and clinical factors using logistic
      regression. RESULTS: Among respondents, 59.4% reported taking a cholesterol
      lowering drug, but most were not aware of potential adverse effects. In adjusted
      analyses, drug treatment was significantly more common among women, patients aged
      65 to 69 years, and those who reported that a cardiologist was mainly responsible
      for their cholesterol management. Lowering cholesterol levels was viewed as "very
      important" by 77.2% of respondents, but significantly less often by men, older
      patients, and those with diabetes mellitus or congestive heart failure. Only
      33.1% of respondents knew their cholesterol level, and this knowledge was
      significantly less common among black patients and those with diabetes mellitus
      or congestive heart failure. CONCLUSIONS: Use of cholesterol-lowering drugs was
      much greater than in previous studies of elderly patients after myocardial
      infarction, demonstrating increased attention to secondary prevention. However,
      most patients were unaware of their cholesterol level or potential adverse
      effects of drug treatment, indicating that they may benefit from greater
      education about cholesterol testing and treatment.

PMID- 11996612
TI  - Characteristics of bacteremia between community-acquired and nosocomial
      Klebsiella pneumoniae infection: risk factor for mortality and the impact of
      capsular serotypes as a herald for community-acquired infection.
AB  - BACKGROUND: Although several epidemiological surveys of Klebsiella clinical
      isolates have been performed, few studies have correlated the clinical isolate
      with disease. OBJECTIVE: To compare the clinical and bacteriological
      characteristics of Klebsiella pneumoniae bacteremia acquired as community or
      nosocomial infections. METHODS: We prospectively enrolled 158 consecutively
      hospitalized patients with K pneumoniae bacteremia. Clinical data were reviewed.
      Antimicrobial susceptibility testing and capsular serotyping were performed. We
      used the chi(2) test, the Fisher exact test, or the t test for statistic
      analysis. RESULTS: Underlying diabetes mellitus was more common in community
      acquired than in nosocomial infection (46/94 [49%] vs. 8/64 [12%]; P<.001). On
      the other hand, neoplastic disease (34/64 [53%] vs. 13/94 [14%]; P<.001) and
      antibiotic resistance (P<.01) were more frequent in patients with nosocomial
      compared with community-acquired infections. Klebsiella pneumoniae liver
      abscesses, which were all community acquired, accounted for the source of 22
      (23%) of 94 community-acquired K pneumoniae infections. No attributable source of
      infection was found for 37 (58%) of the 64 nosocomial infections vs. 15 (16%) of
      the 94 community-acquired infections. Only 58 isolates (36.7%) could be
      serotyped; of these, capsular serotypes K1, K2, and K28 accounted for 37 (23.4%),
      8 (5.1%), and 6 (3.8%), respectively, of all strains. However, typeable isolates
      were significantly more common among community-acquired than nosocomial isolates
      (42/94 [45%] vs. 16/64 [25%]; P =.01), especially for serotype K1 (28/94 [30%]
      vs. 9/64 [14%]; P =.02). Significant risk factors for mortality included
      nosocomial infection, lung infection, thrombocytopenia, leukopenia, ceftazidime
      resistance, inappropriate antimicrobial therapy, and septic shock. CONCLUSIONS:
      Significant differences were identified between community-acquired and nosocomial
      K pneumoniae bacteremia. Ceftazidime resistance in nosocomial K pneumoniae
      bacteremia carried a high risk for mortality, and serotype K1 in K pneumoniae was
      more prevalent in community-acquired infection, suggesting more virulence.

PMID- 11996613
TI  - Relevance of mutations in the TLR4 receptor in patients with gram-negative septic
      shock.
AB  - BACKGROUND: Septic shock remains a significant health concern worldwide, and
      despite progress in understanding the physiological and molecular basis of septic
      shock, the high mortality rate of patients with septic shock remains unchanged.
      We recently identified a common polymorphism in toll-like receptor 4 (TLR4) that
      is associated with hyporesponsiveness to inhaled endotoxin or lipopolysaccharide
      in humans. METHODS: Since TLR4 is a major receptor for lipopolysaccharide in
      mammals and gram-negative bacteria are the prevalent pathogen associated with
      septic shock, we investigated whether these specific TLR4 alleles are associated
      with a predisposition to a more severe disease outcome for patients with septic
      shock. We genotyped 91 patients with septic shock as well as 73 healthy blood
      donor controls for the presence of the TLR4 Asp299Gly and TLR4 Thr399Ile
      mutations. RESULTS: We found the TLR4 Asp299Gly allele exclusively in patients
      with septic shock (P =.05). Furthermore, patients with septic shock with the TLR4
      Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections.
      CONCLUSION: Mutations in the TLR4 receptor may predispose people to develop
      septic shock with gram-negative microorganisms.

PMID- 11996614
TI  - Autoimmune thrombocytopenic Purpura and Helicobacter pylori infection.
AB  - BACKGROUND: The mechanisms triggering the production of platelet autoantibodies
      in autoimmune thrombocytopenic purpura (AITP) are poorly understood. Recently,
      marked improvements in platelet counts have been reported in patients with AITP
      and concurrent Helicobacter pylori infection after eradication of H pylori by a
      standard antibiotic regimen. We looked for an association between H pylori
      infection and AITP in adults. METHODS: Fifty-one adults of white French origin,
      negative for human immunodeficiency virus (mean +/- SD age, 40 +/- 19.8 years),
      with AITP and a platelet count of less than 50 x 10(3)/microL at onset were
      included. Thirty-five consecutive nonthrombocytopenic patients (mean +/- SD age,
      43 +/- 22 years) of the same origin and with unknown H pylori status served as
      control subjects. Antibodies against H pylori were detected by means of an
      agglutination method in both patients and control subjects. Sex ratio, mean age,
      hemorrhagic manifestations, response to corticosteroid therapy, and final outcome
      were compared in H pylori-negative and H pylori-positive patients with AITP. To
      test for a possible molecular mimicry mechanism, we also used an immunoblot assay
      to look for specific H pylori antibodies in platelet eluates from 3 H pylori
      positive patients with AITP. RESULTS: Seroprevalence of H pylori in patients with
      AITP (15 [29%]) was not significatively different from that in control subjects
      (10 [29%]). The H pylori-positive and H pylori-negative patients with AITP did
      not differ in main characteristics at AITP onset, response rate to
      corticosteroids, and final outcome. None of the 3 patients investigated had H
      pylori antibodies in platelet eluates. CONCLUSION: Although the role of H pylori
      in a subgroup of patients with AITP cannot be excluded, we found no evidence of
      an association between H pylori infection and AITP.

PMID- 11996615
TI  - Alcohol-based handrub improves compliance with hand hygiene in intensive care
      units.
AB  - BACKGROUND: Nosocomial infection is a leading complication in intensive care
      units. Although hand hygiene is the single most efficient preventive measure,
      compliance with this simple action remains low. OBJECTIVES: To assess the effect
      of an intervention to promote hand hygiene and to investigate risk factors for
      noncompliance in intensive care units. METHODS: We performed 7 observational
      surveys and implemented a promotional campaign after baseline in medical,
      surgical, and pediatric intensive care units of a teaching hospital. Health care
      workers were observed during routine patient care. The intervention consisted of
      a hospitalwide promotional campaign, including observation and performance
      feedback, posters display, and distribution of individual bottles of alcohol
      based handrub. The main outcome measure was compliance with hand hygiene through
      handwashing or handrubbing. RESULTS: We observed 2743 opportunities for hand
      hygiene distributed over 248 periods. Overall compliance increased from 38.4% to
      54.5% during the study (P<.001). Although recourse to handwashing remained stable
      at around 30%, handrubbing increased from 5.4% at baseline to 21.7% at the last
      survey (P<.001). Compliance increased among nurses and nursing assistants, but
      remained stable among physicians. Handwashing compliance decreased, on average,
      by 4.7% for an increase of 10 opportunities for hand hygiene per hour of patient
      care (P<.001), whereas no such association existed for handrubbing. CONCLUSIONS:
      Our intervention induced a marked and sustained increase in compliance with hand
      hygiene. In intensive care units, less time-consuming handrubbing might replace
      standard handwashing and overcome the barrier of time constraints.

PMID- 11996616
TI  - Randomized controlled trial of interventions to improve follow-up for latent
      tuberculosis infection after release from jail.
AB  - BACKGROUND: Adherence to treatment of persons with latent tuberculosis infection
      after release from jail has been poor. METHODS: A randomized controlled trial was
      conducted at the San Francisco City and County Jail, San Francisco, Calif.
      Subjects undergoing therapy for latent tuberculosis infection who spoke either
      English or Spanish were randomly allocated to receive education every 2 weeks
      while in jail; an incentive if they went to the San Francisco County Tuberculosis
      Clinic within 1 month of release; or usual care. The main outcome measures were
      completion of a visit to the tuberculosis clinic within 1 month of release and
      completion of therapy. RESULTS: Of 558 inmates enrolled, 325 were released before
      completion of therapy. Subjects in either intervention group were significantly
      more likely to complete a first visit than were control subjects (education
      group, 37%; incentive group, 37%; and controls, 24%) (adjusted odds ratio based
      on pooled results for the education and incentive groups, 1.85; 95% confidence
      interval, 1.04-3.28; P =.02). Those in the education group were twice as likely
      to complete therapy compared with controls (adjusted odds ratio, 2.2; 95%
      confidence interval, 1.04-4.72; P =.04). Of those who went to the tuberculosis
      clinic after release, subjects in the education group were more likely to
      complete therapy (education group, 65% [24/37]; incentive group, 33% [14/42]; and
      control group, 48% [12/25]; P =.02). CONCLUSIONS: Education or the promise of an
      incentive improved initial follow-up. Education was superior to an incentive for
      the completion of therapy. Fairly modest strategies provided in jail can improve
      adherence. Further links between jail health services and community care should
      be explored.

PMID- 11996617
TI  - Factors associated with hypertension control in the general population of the
      United States.
AB  - BACKGROUND: Uncontrolled hypertension is the most common and important risk
      factor for cardiovascular and renal disease. We studied factors associated with
      hypertension control in the Third National Health and Nutrition Examination
      Survey. METHODS: A total of 3077 non-Hispanic whites, 1742 non-Hispanic blacks,
      and 1067 Mexican Americans 18 years or older with hypertension were included in
      the current analysis. Blood pressure was measured by trained observers by means
      of a standard mercury sphygmomanometer, and controlled hypertension was defined
      as a mean systolic/diastolic blood pressure less than 140/90 mm Hg. RESULTS:
      Percentages of persons with controlled hypertension differed significantly by
      ethnicity and sex: 19.2% and 28.7% for white men and women, 17.5% and 28.6% for
      black men and women, and 12.7% and 18.0% for Mexican American men and women,
      respectively. After adjustment for important covariables, percentages of persons
      with controlled hypertension were significantly higher among persons who were
      currently (odds ratio [OR] 2.39; 95% confidence interval [CI], 1.52-3.74) or
      formerly (OR, 1.81; 95% CI, 1.12-2.93) married, had private health insurance (OR,
      1.59; 95% CI, 1.02-2.49), visited the same facility for their health care (OR,
      2.77; 95% CI, 1.88-4.09) or saw the same provider for their health care (OR,
      2.29; 95% CI, 1.74-3.02), had their blood pressure checked during the preceding 6
      months (OR, 8.00; 95% CI, 3.75-17.1) or 6 to 11 months (OR, 5.31; 2.51-11.2), and
      reported using lifestyle modification to control their hypertension (OR, 6.02;
      95% CI, 4.20-8.63). CONCLUSION: These data strongly suggest that access to a
      regular source of health care and modification of lifestyle are important factors
      in the control of hypertension in the community.

PMID- 11996618
TI  - Causes of death for patients with community-acquired pneumonia: results from the
      Pneumonia Patient Outcomes Research Team cohort study.
AB  - BACKGROUND: To our knowledge, no previous study has systematically examined
      pneumonia-related and pneumonia-unrelated mortality. This study was performed to
      identify the cause(s) of death and to compare the timing and risk factors
      associated with pneumonia-related and pneumonia-unrelated mortality. METHODS: For
      all deaths within 90 days of presentation, a synopsis of all events preceding
      death was independently reviewed by 2 members of a 5-member review panel (C.M.C.,
      D.E.S., T.J.M., W.N.K., and M.J.F.). The underlying and immediate causes of death
      and whether pneumonia had a major, a minor, or no apparent role in the death were
      determined using consensus. Death was defined as pneumonia related if pneumonia
      was the underlying or immediate cause of death or played a major role in the
      cause of death. Competing-risk Cox proportional hazards regression models were
      used to identify baseline characteristics associated with mortality. RESULTS:
      Patients (944 outpatients and 1343 inpatients) with clinical and radiographic
      evidence of pneumonia were enrolled, and 208 (9%) died by 90 days. The most
      frequent immediate causes of death were respiratory failure (38%), cardiac
      conditions (13%), and infectious conditions (11%); the most frequent underlying
      causes of death were neurological conditions (29%), malignancies (24%), and
      cardiac conditions (14%). Mortality was pneumonia related in 110 (53%) of the 208
      deaths. Pneumonia-related deaths were 7.7 times more likely to occur within 30
      days of presentation compared with pneumonia-unrelated deaths. Factors
      independently associated with pneumonia-related mortality were hypothermia,
      altered mental status, elevated serum urea nitrogen level, chronic liver disease,
      leukopenia, and hypoxemia. Factors independently associated with pneumonia
      unrelated mortality were dementia, immunosuppression, active cancer, systolic
      hypotension, male sex, and multilobar pulmonary infiltrates. Increasing age and
      evidence of aspiration were independent predictors of both types of mortality.
      CONCLUSIONS: For patients with community-acquired pneumonia, only half of all
      deaths are attributable to their acute illness. Differences in the timing of
      death and risk factors for mortality suggest that future studies of community
      acquired pneumonia should differentiate all-cause and pneumonia-related
      mortality.

PMID- 11996619
TI  - Using trade names: a risk factor for accidental drug overdose.
AB  - Medication errors due to the exclusive use of trade names of drugs may lead to
      life-threatening complications. We report the case of a patient with verapamil
      overdose as a result of this. This case illustrates that the use of trade names,
      omitting the international nonproprietary names of the active moiety, carries the
      risk of serious adverse drug events by overdose.

PMID- 11996620
TI  - Let's strip the king: eligibility not safety is the problem of anticoagulation
      for stroke prevention in elderly patients with atrial fibrillation.

PMID- 11996622
TI  - Prevalence of gastrointestinal symptoms in patients with type 2 diabetes: a
      population-based study.

PMID- 11996624
TI  - Weight loss: goals, realities, and strategies.

PMID- 11996625
TI  - Are there benefits from long-term pharmacotherapy of obesity?

PMID- 11996626
TI  - Statins: balancing benefits, efficacy and safety.
AB  - Coronary heart disease (CHD) is the leading cause of death in the US. The risk of
      CHD is substantially increased in people with elevated levels of low-density
      lipoprotein cholesterol (LDL-C). The 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase inhibitors (statins) are the most effective drug class for
      lowering LDL-C. Long-term prospective studies have shown that statin therapy
      significantly reduces the risk of CHD morbidity and mortality in patients without
      or with evidence of established CHD (primary and secondary prevention,
      respectively). In 1988, treatment guidelines were first issued by the National
      Cholesterol Education Program Adult Treatment Panel I (NCEP-ATP I), then revised
      in 1993 (ATP II), to provide recommendations for the prevention and management of
      high cholesterol in adults. Despite these guidelines, recent national surveys
      have shown that effective therapies are being under-utilised and they often fail
      to achieve LDL-C goals established by NCEP-ATP II. The reasons appear to be
      multifactorial but include issues related to efficacy, safety, the potential for
      adverse drug reactions, failure to prescribe appropriate medication or dose and
      noncompliance with therapy. In the first major update of NCEP guidelines in
      almost a decade, the current ATP III recommendations have placed an increased
      number of Americans in the high-risk category, inviting even more aggressive
      therapy and escalating the challenge of reaching NCEP goals. New statins that may
      have even greater efficacy and less potential for drug interactions may help
      address some concerns associated with the failure to achieve treatment goals.

PMID- 11996627
TI  - Psychotropic drugs and the ECG: focus on the QTc interval.
AB  - The QT interval measuring depolarisation and repolarisation has, when lengthened,
      been implicated as a risk factor for the development of torsades de pointes and
      sudden death, particularly in patients predisposed to these complications due to
      cardiovascular impairment. Since some of the medications used in psychiatry have
      been implicated, an extensive review of available literature was made of the
      major classes, including antipsychotics, antidepressants, lithium,
      anticonvulsants and benzodiazepines. Further, where no publications were found on
      a particular medication, the pharmaceutical firms responsible for these items
      were contacted concerning possibly unpublished data. Results of the survey
      indicate that there may be difficulty in one of three situations: immediate (in
      the first minutes to hours after oral or parenteral administration), short-term
      use of 4 - 12 weeks or long-term use of 6 months. Based on this approach, the
      greatest concern is directed at the immediate application of haloperidol,
      droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide,
      sertindole, nortriptyline, clomipramine, doxepin and the long-term use of
      clozapine, olanzapine and carbamazepine. It is of interest that a reduction in
      QTc is reported with aripiprazole. Among the antidepressants, the tertiary
      tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have
      a more general impact, while the secondary tricyclic antidepressants
      (nortriptyline, desipramine) may impact more on children and the elderly. Among
      other antidepressants, the only reports of torsades de pointes appeared to occur
      with mirtazapine. It was also of interest to find data showing no effect or
      reductions in QTc produced by sertraline, citalopram, paroxetine and bupropion in
      multiple studies. Effects of medications on other heart parameters are also
      briefly reviewed. In particular, the safety of sertraline in post-MI patients and
      of bupropion in heart disease patients is highlighted. Little information was
      available on other classes of medications used in psychiatric disorders. What is
      available concerning lithium, the anticonvulsants and the benzodiazepines
      indicates little effect on the QTc, although there may be effects on other
      cardiovascular parameters.

PMID- 11996628
TI  - The prevention of sudden death in hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a familial myocardial disease caused by
      mutations in cardiac sarcomeric proteins. HCM is characterised by myocyte
      disarray and myocardial fibrosis. Most patients are largely asymptomatic but some
      are prone to a number of disease-related complications, the most problematic of
      which is sudden cardiac death. Diagnosing patients who are at risk has not been
      easy because of the clinical heterogeneity of the disease, the frequent absence
      of symptoms prior to sudden cardiac death and the relatively low disease
      prevalence and annual mortality rates. To date, both low-dose amiodarone and
      internal cardioverter/defibrillator implantation have been advocated in high-risk
      individuals. Further improvements in clinical understanding and risk
      stratification are necessary to identify HCM patients who are at high risk of
      sudden death.

PMID- 11996629
TI  - Vasopressin in cardiovascular patients: therapeutic implications.
AB  - Vasopressin is a vital homeostatic protein which regulates fluid balance via its
      antidiuretic effects and vascular tone via its vasoconstrictive effects.
      Endogenous vasopressin deficiency has been implicated in several disease states
      resulting in vasodilatory shock. In particular, vasopressin levels are low in
      patients following cardiac surgery and in those with ventricular dysrhythmias.
      Several recent studies have demonstrated the effectiveness of exogenous
      vasopressin in providing haemodynamic support in patients with
      postcardiopulmonary bypass vasodilatory shock and refractory ventricular
      fibrillation. This manuscript reviews the pathophysiological and clinical basis
      for vasopressin replacement in patients with cardiovascular collapse.

PMID- 11996630
TI  - Immunosuppressive therapy of childhood idiopathic nephrotic syndrome.
AB  - Childhood nephrotic syndrome (NS) is a distressing chronic renal disorder with
      potentially life threatening complications. Over 80% of cases in children are due
      to minimal change disease and the majority will respond to corticosteroid
      therapy. Steroid-sensitive NS is considered a relatively benign condition, since
      progression to end stage renal failure (ESRF) is extremely rare and > 80% will
      enter spontaneous long-term remission in later childhood. However, the disease is
      characterised by a relapsing course, placing the child at risk of acute
      complications, such as infection, hypovolaemia and thrombosis. Frequent relapses
      can result in a not inconsequential corticosteroid burden or prescription of
      cytotoxic immunosuppressive therapy to control the disease. In contrast, steroid
      resistant and -refractory NS has an unfavourable outcome with a propensity to
      progress to ESRF. While these clinical entities have an unpredictable response to
      cytotoxic immunosuppressive therapy, the favourable long-term renal survival
      associated with children who enter sustained remission has revived the enthusiasm
      to treat steroid-resistant NS with more aggressive immunosuppressive regimens.

PMID- 11996631
TI  - Treatment of malignant hypercalcaemia.
AB  - Hypercalcaemia is a common paraneoplastic syndrome caused by the production by
      tumours of several factors which affect bone resorption and/or tubular calcium
      reabsorption. Antihypercalcaemic therapy in cancer patients involves rehydration
      manoeuvres, as well as the use of a variety of available drugs which inhibit bone
      resorption, namely plicamycin, calcitonin, bisphosphonates and gallium nitrate.
      While plicamycin is currently out of use because of its considerable toxicity,
      bisphosphonates have become the standard therapy in hypercalcaemia of malignancy
      (HM). These compounds are potent inhibitors of bone resorption but they do not
      affect tubular calcium reabsorption, which limits their efficacy in humoral HM
      (HHM) cases. In these patients, gallium nitrate should be the therapy of choice.
      Among the available bisphosphonates, pamidronate administered in a single
      infusion of 90 mg, normalises serum calcium levels in > 90% of HM patients. A
      recently introduced bisphosphonate, zoledronate, is likely to replace pamidronate
      as a first-line therapy in these patients. The effectiveness of calcitonin in HM
      treatment is limited, although it seems to be useful at the outset in cases with
      severe symptomatic hypercalcaemia. Future treatment options of HM are likely to
      include new bone resorption inhibitors, for example, naturally-occurring
      osteoprotegerin, or alternate approaches aimed at reducing the tumour production
      of parathyroid hormone-related protein with noncalcaemic analogues of calcitriol
      or ras-isoprenylation inhibitors. The development of putative therapeutic agents
      targeted to inhibit distal calcium reabsorption should be valuable in the
      management of HHM cases.

PMID- 11996632
TI  - Thiazolidinediones in the treatment of type 2 diabetes.
AB  - In the last few years there has been an explosion of research that has improved
      our understanding of the pathogenesis of Type 2 diabetes mellitus (DM-2) and has
      led to the development of new oral antidiabetic drugs. Thiazolidinediones (TZDs)
      are the newest of these antidiabetic agents. TZDs are insulin sensitisers that
      depend on the presence of insulin for their action. They target insulin
      resistance, which is thought to play a central role in DM-2 and the associated
      metabolic syndrome characterised by central obesity, hypertension, dyslipidemia
      and hypercoagulability, all leading to increased cardiovascular morbidity and
      mortality. As a result, TZDs have the potential to improve other conditions
      associated with the metabolic syndrome, in addition to their glycaemic action.
      TZDs act by activating peroxisome proliferator-activated receptor (PPAR) phi a
      nuclear receptor implicated not only in lipid and glucose metabolism but other
      physiological functions as well. TZDs may have wide clinical applications beyond
      DM-2, as they can potentially be used to treat other conditions associated with
      insulin resistance and PPAR-phi receptors, such as impaired glucose tolerance,
      polycystic ovarian syndrome and HIV lipodystrophy.

PMID- 11996633
TI  - Update on ocular allergy treatment.
AB  - Allergy affects > 15% of the world population with a higher prevalence of 30% in
      westernised industrialised countries, such as the US. Allergy commonly affects
      various target organs including the eyes, nose, sinuses, ears, lungs and skin.
      However, the ocular component may be the most common and initially the most
      prominent disabling feature. Some patients are affected for only a few weeks to
      months while others have symptoms that last throughout the year. The associated
      healthcare costs related to allergic conjunctivitis has been commonly nestled
      with allergic rhinitis and has been reported to be as high as US$5.9 billion in
      the US, with 25% (US$1.5 billion) of it related to medication use. The
      expenditures related to ocular prescription medication has only recently risen in
      the past decade from US$6 million in early 1990s to > US$200 million in the new
      millennium with a projected continuous expansion of 25% per year. This appears to
      be due to improved prescription medications and their clear benefit over the less
      efficacious over-the-counter products. The actual cost of the medications and
      their relative price increases over the past year have ranged from 0 - 49% with
      an average cost of < US$ day. The newer topical medications (multiple acting
      agents) are focusing on multiple actions that include an antihistaminic effect to
      provide an immediate relief and additional delayed effects to act on the
      mediators of the late phase reaction without steroid side effects (glaucoma,
      cataracts). The paradigm for the treatment of ocular allergy ranges from primary
      measures (avoidance measures, cold compresses and lubrication), to secondary
      measures (various combination of topical agents) and tertiary measures that would
      include topical steroids and immunotherapy. The increased interest in advancing
      ocular treatment will lead to the development of additional therapies, novel
      pharmacokinetic delivery systems and, thus, improved healthcare outcomes for
      patients with allergic conjunctivitis.

PMID- 11996634
TI  - The pharmacological treatment of anxiety disorders in children and adolescents.
AB  - As the recognition of paediatric and adolescent anxiety disorders improves, so
      does the number of recommended treatments. Newer medications (chiefly
      serotonergic antidepressants) have emerged as the pharmacological treatment of
      choice and have largely replaced benzodiazepines and tricyclic antidepressants
      (TCAs) for these disorders. This review will focus on placebo-controlled and open
      label studies concerning the treatment of anxiety in children and adolescents,
      comparing data from newer antidepressant medications (plus buspirone) with data
      on TCAs and benzodiazepines in this population. There are few randomised, placebo
      controlled trials of medications for anxiety in children and adolescents, with
      most data coming from open-label trials and case series. Moreover, there are no
      studies comparing pharmacological versus behavioural treatments. Most recent data
      concerning the efficacy of selective serotonin reuptake inhibitors suggests that
      these agents will be effective and safe in the treatment of paediatric anxiety
      disorders. The potential side effect profiles of these newer agents also makes
      them an attractive first choice for anxiety when compared to the benzodiazepines
      or TCAs, each of which poses its own potentially serious adverse effects. More
      research is needed in the area of psychopharmacological treatments for paediatric
      and adolescent anxiety, not only to substantiate the current beliefs that
      serotonergic agents are effective and safe but to pinpoint the factors that might
      predict responses to particular agents or classes of medications. Future
      investigations should focus on treatments which have already proven effective for
      adult anxiety disorders (both medications and psychotherapies), given the
      apparent links between paediatric and adult anxiety disorders.

PMID- 11996635
TI  - The future of pharmacotherapy for paediatric anxiety.
AB  - There is a growing body of data supporting the use of pharmacological agents in
      the treatment of paediatric anxiety. The most compelling data exists for the use
      of selective serotonin re-uptake inhibitors. However, questions the safe and
      efficacious use of medications with anxiolytic properties still remain. Although
      the field has progressed in the past several years, it is evident that more
      research needs to be done in the future.

PMID- 11996636
TI  - Review of enoxaparin and its clinical applications in venous and arterial
      thromboembolism.
AB  - Venous and arterial thromboembolic disorders are common medical conditions that
      are associated with considerable morbidity and mortality. Unfractionated heparin
      (UFH) and its derivatives, the low molecular weight heparins (LMWHs), are the
      anticoagulants of choice when a rapid anticoagulant effect is required. LMWHs
      have several advantages over UFH, including a longer plasma half-life and higher
      bioavailability; a predictable dose response, which enables once- or twice-daily
      dosing; and a more convenient route of administration (subcutaneous instead of
      intravenous), which enables patients to self-inject in an out-patient setting.
      Enoxaparin is a LMWH prepared by alkaline hydrolysis of the benzylin ester of
      UFH. The efficacy of enoxaparin in the management of venous and arterial
      thromboembolism has been shown in a wide range of patient groups using doses
      ranging from fixed doses of 20 - 60 mg o.d. and 0.75 - 1.5 mg/kg b.i.d. Other
      doses, such as 80 mg/day for pregnant women with combined thrombophilic defects,
      have also been studied. The use of subcutaneous enoxaparin as an effective and
      safe home treatment for patients with acute proximal deep vein thrombosis (DVT)
      has been demonstrated. The benefits of preventing venous thromboembolic events
      with enoxaparin include reducing the costs associated with investigating the
      symptoms of DVT, acute treatment and hospitalisation, and potentially the
      development of post-thrombotic syndrome, while improving quality of life and so
      making the treatment cost effective. In contrast to other LMWHs, enoxaparin has
      been shown to provide better outcomes than UFH in the treatment of unstable
      angina and non-ST-segment elevation myocardial infarction, without increasing
      major bleeding. Adverse events with enoxaparin are infrequent; the most common
      events are minor bleeding complications. It should be noted that different doses
      or indications are approved in each country.

PMID- 11996637
TI  - Orlistat in the treatment of Type 2 diabetes mellitus.
AB  - The prevalence of Type 2 diabetes mellitus (DM-2) is increasing throughout the
      world and poses a major public health concern. With the majority of patients DM-2
      are overweight or obese and weight loss is generally recommended, both as a first
      line therapy and as an adjunct to pharmacological therapies. However, it is
      generally acknowledged that weight loss, a difficult goal for many overweight and
      obese individuals, is especially difficult for those with DM-2 and there is
      interest in whether pharmacological adjuncts may be useful for this purpose.
      Orlistat is an intestinal lipase inhibitor previously approved for the treatment
      of obesity. During the past several years, clinical trials have been completed
      concerning the use of orlistat in the treatment of overweight or obese patients
      with DM-2. The purpose of this review is to examine the results of these clinical
      trials. Data on > 2500 orlistat-treated patients with DM-2 are reviewed and
      summarised. Orlistat therapy led to greater weight loss and improved metabolic
      control in overweight and obese patients with DM-2.

PMID- 11996638
TI  - Letrozole in the treatment of breast cancer.
AB  - Over the last 30 years the role of tamoxifen in breast cancer treatment has been
      progressively expanded by clinical investigation to encompass the entire spectrum
      of disease from cancer chemoprevention to palliation of advanced disease. The
      primacy of tamoxifen for these indications in postmenopausal women is now under
      challenge by the selective aromatase inhibitors, a class of endocrine agent that
      induces oestrogen deprivation rather than oestrogen receptor blockade. This
      review considers the biochemical, pharmacological and clinical properties of the
      nonsteroidal aromatase inhibitor letrozole. This agent is superior to tamoxifen
      for the treatment of metastatic breast cancer, a finding that suggests that
      letrozole may ultimately eclipse tamoxifen for other indications, including
      chemoprevention. Further clinical investigation will be necessary to establish
      the risks and benefits of letrozole versus tamoxifen for each new indication,
      with adjuvant therapy being the next in line. The object of this review is to
      provide a reference source on the biochemical, pharmacological and clinical
      properties of letrozole for clinicians to consider both established and future
      indications.

PMID- 11996639
TI  - Trizivir.
AB  - Treatment of HIV infection has typically been carried out using two nucleoside
      analogues and a protease inhibitor (PI). Such regimens can be complex and have
      high pill burdens. Use of alternative regimens, such as triple nucleoside based
      regimens, can improve adherence and decrease toxicities associated with PI
      therapy. Trizivir is a combination tablet of zidovudine, lamivudine and abacavir.
      This formulation allows a dosing schedule of one pill twice-daily. The components
      of have performed favourably compared to PI-based regimens, such as indinavir.
      However, in one study the individual components of Trizivir did not suppress HIV
      1 viral replication as well as the PI-based regimen in a subset of patients with
      very high HIV-1 plasma RNA. Trizivir also avoids side effects of antiretroviral
      therapy, such as hyperlipidaemia, but its use is associated with a
      hypersensitivity reaction in a small number of patients. Trizivir is an important
      part of the HIV armamentarium. The potency and ease of administration of Trizivir
      make it worth consideration in HIV therapy, either by itself or in combination
      with other agents.

PMID- 11996640
TI  - Class benefits of AT(1) antagonists in Type 2 diabetes with nephropathy.
AB  - Diabetes mellitus has reached epidemic proportions in many countries and is the
      most common cause of end stage renal disease (ESRD). The angiotensin II receptor
      1 (AT(1)) antagonists losartan and irbesartan have recently been evaluated as
      renoprotective agents in large clinical trials of patients with Type 2 diabetes
      and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes
      mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased
      the number of patients reaching the primary end point of a composite of measures
      of neuropathy. The relative risk reduction was approximately 15% with losartan
      and this was due to a reduction in both the doubling of creatinine concentration
      (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy
      Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling
      of the baseline creatinine concentration (37% risk reduction) but there was also
      a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality.
      Beneficial effects occurred in addition to blood pressure being controlled by
      agents other than the AT(1) antagonists. These clinical trials suggest that there
      may be a class renoprotective action with AT(1) antagonists, although the
      mechanism is not clear. Patients with Type 2 diabetes and nephropathy should
      receive either an AT(1) antagonist or the angiotensin converting enzyme inhibitor
      ramipril to ensure renoprotection.

PMID- 11996641
TI  - The 93rd Annual Meeting of the American Association for Cancer Research. 6-10
      April 2002, San Francisco, California, USA.
AB  - The American Association for Cancer Research held its 93rd Annual Meeting on 6 -
      10 April 2002. This was an enormous meeting with approximately 14,000 registrants
      and some 5750 abstracts, the vast majority of which were presented as posters.
      Those abstracts judged to be of particular significance or interest were
      presented as 15-min platform presentations in minisymposia, of which there were
      36 during the meeting. In addition to this, there was a full day of 15
      educational sessions (each with three to four speakers), 11 award lectures, 47
      early morning Meet-the-Expert Sunrise Sessions. There was a mind-boggling array
      of choices for those interested in cancer research. This meeting was the largest
      ever convened on a single disease. We will endeavour to provide some of the
      highlights of this exciting meeting.

PMID- 11996642
TI  - Nitric oxide donor drugs: current status and future trends.
AB  - Nitric oxide synthesised in endothelial cells that line blood vessels has a wide
      range of functions that are vital for maintaining a healthy cardiovascular
      system. Reduced nitric oxide availability is implicated in the initiation and
      progression of many cardiovascular diseases and delivery of supplementary nitric
      oxide to help prevent disease progression is an attractive therapeutic option.
      Nitric oxide donor drugs represent a useful means of systemic nitric oxide
      delivery and organic nitrates have been used for many years as effective
      therapies for symptomatic relief from angina. However, nitrates have limitations
      and a number of alternative nitric oxide donor classes have emerged since the
      discovery that nitric oxide is a crucial biological mediator. This review focuses
      on novel advances and possible future directions in nitric oxide donor drug
      development.

PMID- 11996643
TI  - Pharmacological interventions for stroke: failures and future.
AB  - Given the few options currently available for patients following ischaemic
      stroke, the recent disappointing failures of several large-scale Phase III
      clinical trials has made the search for novel therapeutic approaches even more
      critical. Experimental evidence has suggested that the majority of stroke
      patients have a slow evolution of brain injury which can occur over several
      hours. Progressive microcirculatory failure following the initial onset of
      ischaemia may contribute to the expansion of brain injury. Included among the
      pathophysiological changes that are speculated to occur as a secondary response
      to the initial ischaemia are free radical production, excitotoxicity (for
      example, glutamate) disruption of ionic homeostasis (for example, sodium and
      calcium influx), enzymatic changes, stimulation of the inflammatory process,
      endothelin release, activation of platelets and leukocytes, delayed coagulation
      and endothelial dysfunction. All of these pathophysiological reactions could
      contribute to an increase in local vascular resistance and therefore cause
      progressive hypoperfusion of the brain following the onset of stroke. The scope
      of this review will focus on recent clinical failures in addition to agents
      currently in clinical development, comparing vascular targets to the common
      neuroprotective strategies.

PMID- 11996644
TI  - Partial fatty acid oxidation inhibitors for stable angina.
AB  - Partial fatty acid oxidation inhibition is effective therapy for the treatment of
      chronic stable angina and is particularly useful in patients with persistent
      angina despite optimal traditional therapy. The heart derives most of its energy
      from the oxidation of fatty acids. Fatty acid oxidation strongly inhibits
      pyruvate oxidation in the mitochondria and the uptake and oxidation of glucose.
      The primary effect of demand-induced ischaemia is impaired aerobic formation of
      ATP in the mitochondria, resulting in activation of non-oxidative glycolysis and
      lactate production, despite a relatively high residual myocardial oxygen
      consumption and continued reliance on fatty acid oxidation. Traditional drugs for
      chronic stable angina act by reducing the use of ATP through suppression of heart
      rate and blood pressure or by increasing aerobic formation of ATP by increasing
      coronary blood flow. Partial inhibition of fatty acid oxidation increases glucose
      and pyruvate oxidation and decreases lactate production, resulting in higher pH
      and improved contractile function during ischaemia. These agents do not affect
      heart rate, coronary blood flow or arterial blood pressure. Clinical trials with
      ranolazine or trimetazidine, either alone or in combination with a Ca2+ channel
      antagonist or a beta-adrenergic receptor antagonist, have demonstrated reduced
      symptoms of exercise-induced angina.

PMID- 11996645
TI  - The therapeutic potential of dopamine modulators on the cardiovascular and renal
      systems.
AB  - In the periphery, physiological dopamine increases renal blood flow, decreases
      renal resistance and acts on the kidney tubule to enhance natriuresis and
      diuresis. The loss of dopamine function may be involoved in the deterioration in
      kidney function associated with ageing and may have a role in the pathogenesis of
      hypertension and diabetes. Intravenous dopamine is used as a positive inotrope in
      the treatment of acute heart failure and cardiogenic shock and as a diuretic in
      renal failure. The clinical uses of dopamine are limited, as it must be given
      intravenously, and also has widespread effects. The levels of peripheral dopamine
      can be increased by the administration of L-dopa to increase synthesis, prodrugs
      to release dopamine (docarpamine, glu-dopa) or by inhibiting the breakdown of
      dopamine (nitecapone). Preliminary clinical trials suggest that docarpamine may
      be useful in patients with low cardiac output syndrome after cardiac surgery and
      in refractory cirrhotic ascites. Ibopamine is an agonist at dopamine D1 and D2
      receptors, which may retard the progression of chronic renal failure. Glu-dopa is
      selective for the kidney, thus avoiding widespread side effects. The early
      clinical studies with ibopamine as a diuretic in heart failure were favourable
      but the subsequent large mortality study showed that ibopamine increased
      mortality. Fenoldopam is a selective dopamine D1 receptor agonist. Intravenous
      fenoldopam may be useful in the treatment of hypertension associated with
      coronary artery bypass surgery or in hypertensive emergencies. Although our
      understanding of physiological and pathological roles of peripheral dopamine has
      been increasing rapidly in recent times, we still need more information to allow
      the design of clinically useful drugs that modify these roles. One priority is an
      orally-active selective dopamine D1 receptor agonist.

PMID- 11996646
TI  - Developing treatment for sickle cell disease.
AB  - Sickle cell disease pathophysiology results from sickle haemoglobin
      polymerisation and its effects on the sickle erythrocyte and the vasculature.
      Many of the abnormalities of sickle cell disease are secondary to the damage
      caused by the polymer and the injured red cell. Pharmacological treatment of the
      disease is focused on the inhibition of sickle haemoglobin polymerisation,
      prevention or repair of red cell dehydration and interruption of the interaction
      of sickle cells with the endothelium.

PMID- 11996647
TI  - Myocardial remodelling: pharmacological targets.
AB  - Despite considerable progress in therapy, the progressive augmentation of
      lifespan makes cardiac remodelling and its consequence, heart failure, a major
      cause of mortality and morbidity. Heart failure is consequently becoming a major
      goal in pharmacological research. New approaches include converting enzyme
      inhibitors, beta-blockers and anti-aldosterones and have demonstrated that
      cardiac remodelling is, at least partly, a reversible process. This review aims
      to establish a strategy for therapeutic research which is based on the recent
      advances on the molecular mechanisms of cardiac remodelling, and also to evaluate
      some of the new developments which are presently in progress, including new
      inotropic drugs, new receptors or signals blockers, nitric oxide donors,
      metalloproteinases and apoptotic inhibitors. Our view is clearly evolutionary and
      several of our conclusions may contradict current opinions, such as those which
      consider hypertrophy a detrimental process, hormones as a primary cause of
      cardiac remodelling or inotropic interventions as beneficial.

PMID- 11996648
TI  - Enzyme replacement therapy for the mucopolysaccharide storage disorders.
AB  - The mucopolysaccharide storage disorders are a group of lysosomal storage
      disorders associated with deficiencies of lysosomal enzymes required for the
      normal sequential degradation of glycosaminoglycans, formerly known as
      mucopolysaccharides. The accumulation of glycosaminoglycans in a wide variety of
      tissues results in a complex and progressive disease leading to death in the
      first or second decade in most patients. Studies of enzyme replacement in animal
      models of mucopolysaccharide disorders have demonstrated the potential of
      parenterally administered enzyme to reduce glycosaminoglycan storage and
      microscopic pathology. Clinical studies of enzyme replacement therapy are
      currently underway for mucopolysaccharidosis I, mucopolysaccharidosis VI and
      mucopolysaccharidosis II. The complexity and heterogeneity of the
      mucopolysaccharide disorders provide significant challenges for clinical study
      design and evaluation. Innovative clinical development strategies may be needed
      to lower the development cost and time for complex rare disease therapies to
      assure that such patients receive therapies they deserve.

PMID- 11996649
TI  - Inhaled insulin: a novel route for insulin delivery.
AB  - Insulin has been in use for the treatment of patients with diabetes mellitus for
      over 75 years. However, despite the known benefits of tight glycaemic control,
      multiple insulin injections have still not gained widespread clinical acceptance.
      Although there have been attempts to find effective non-invasive routes for
      insulin delivery, none of the novel non-invasive approaches have become part of
      established practice. In fact, until recently it was believed that as a result of
      limitations, non-invasive insulin was not a clinically realistic option. However,
      preliminary studies have indicated that inhaled insulin may emerge as an
      effective, well-tolerated, non-invasive alternative to subcutaneous regular
      insulin. The pharmacokinetics of inhaled insulin show a more physiological
      profile compared to conventional insulin; however, further studies to confirm
      long-term pulmonary safety and efficacy are needed.

PMID- 11996650
TI  - Non-invasive imaging of plaque vulnerability: an important tool for the
      assessment of agents to stabilise atherosclerotic plaques.
AB  - Disruption of a vulnerable atherosclerotic plaque is well-recognised as the
      primary cause of stroke, non-fatal myocardial infarction and sudden cardiac
      death. Novel therapeutic agents are being developed to stabilise such plaques.
      The initial evaluation of these drugs would be facilitated by the use of non
      invasive imaging techniques to identify vulnerable plaque and document serial
      changes in plaque stability. The aim of this review is to explain the
      characteristics of the leading non-invasive imaging modalities and discuss their
      role in examining the vulnerable plaque. This knowledge will be extremely
      important for physicians and scientists involved in the clinical evaluation of
      novel agents to stabilise the vulnerable plaque.

PMID- 11996651
TI  - Angiotensin II Type 1 receptor antagonists in chronic heart failure.
AB  - Angiotensin II Type 1 receptor antagonists share most but not all of their
      pharmacological actions with angiotensin-converting enzyme inhibitors. The latter
      belong to standard heart failure therapy, with proven benefit in terms of
      morbidity and mortality. Promising data have been provided for angiotensin II
      Type 1 receptor antagonists in experimental models of heart failure. In patients
      with hypertension and those with diabetic nephropathy, favourable results have
      been observed with regards to blood pressure control, reversibility of structural
      changes or prevention of progression of disease. The currently available clinical
      trials in heart failure patients with angiotensin II Type 1 receptor antagonists
      suggest that they may be equivalent to angiotensin-converting enzyme inhibitors,
      but superiority has not been proven. There is no doubt about their effectiveness
      with regards to symptoms; however, their effect on hospitalisation and mortality
      is not unequivocally demonstrated. Further trials are warranted, particularly to
      define their role in comparison with and in addition to angiotensin-converting
      enzyme inhibitors and to further characterise heart failure patient populations
      who derive benefit from angiotensin II Type 1 receptor blockers above and beyond
      angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone.

PMID- 11996652
TI  - Immunomodulation with DiNAC-- a new approach to the treatment of atherosclerosis?
AB  - Not all antioxidants reduce atherosclerosis. This may be because atherosclerosis
      has an autoimmune, inflammatory pathogenesis. As probucol is both an antioxidant
      and an immunomodulatory drug, it may be the immunomodulatory effect that
      underlies its ability to reduce atherosclerosis. N,N-Diacetyl-L-cystine is not an
      antioxidant but is immunomodulatory. In the Watanabe-heritable hyperlipidaemic
      rabbit model of familial hypercholesterolaemia, N,N-diacetyl-L-cystine treatment
      does not lower lipid levels but it does reduce atherosclerosis. Immunomodulation
      may be a new approach to the treatment of atherosclerosis.

PMID- 11996653
TI  - Necrosis is an active and controlled form of programmed cell death.
AB  - In all studies on programmed cell death (PCD) and apoptosis as its most showy
      form, this process was considered to be a paradigmatic antithesis to necrotic
      cell death. On one hand, a concept on necrosis as a cellular cataclysm, an
      uncontrolled and passive phenomenon, had been provoked by an enormous bulk of
      experimental data on its inducibility by superphysiological exposures. On the
      other hand, much attention was attracted to a rapidly expanding (from nematodes)
      field of genetic studies on PCD. However, the findings accumulated which
      suggested a likeness rather than the opposition of the necrotic and apoptotic
      forms of elimination of "unwanted" cells. 1. Very diverse pathophysiological
      exposures (stimuli, stresses), such as heat, ionizing radiation, pathogens,
      cytokines cause both forms of cell death in the same cell population. 2. Anti
      apoptotic mechanisms (e.g., Bcl-2) can protect cells from both necrotic and
      apoptotic destruction. 3. Biochemical interventions (e.g., with inhibitors of
      poly-(ADP-riboso)-polymerase) into the signal and executive mechanisms of PCD can
      change the choice of the cell death form. 4. During both necrosis and epigenetic
      programs of apoptotic cell death that need no macromolecular synthesis (e.g., the
      CD95-dependent death), the nucleus plays a passive role. Therefore, necrosis,
      similarly to apoptosis, is suggested to be a form of the programmed cell death.
      However, for the whole body the physiological consequences of apoptosis and
      necrosis are quite different. In the case of apoptosis, all constituents of the
      nucleus and cytoplasm are isolated by an undamaged membrane and then by
      phagocytes together with the membrane-bound "eat me" markers (phosphatidylserine,
      etc.). In other words, the elimination of the cell which has realized its
      apoptotic program remains virtually unnoticed by the body. In the case of
      necrosis, the cytoplasmic content released into the intercellular space provokes
      an inflammatory response, i.e., an activation of resident phagocytes and
      attraction of leukocytes into the necrosis zone. It is suggested that under
      pathophysiological conditions, the necrotic cell destruction should amplify and
      catalyze pathological processes. The experimental data available now suggest that
      a disturbance in the body of optimal balance between the necrotic and apoptotic
      forms of PCD should be a crucial factor in the development of various
      pathophysiological processes associated with inflammation (diabetes, arthritis)
      or with aging (atherosclerosis, neurodegenerative diseases).

PMID- 11996654
TI  - Kinetics of protein aggregation. Quantitative estimation of the chaperone-like
      activity in test-systems based on suppression of protein aggregation.
AB  - The experimental data on the kinetics of irreversible aggregation of proteins
      caused by exposure to elevated temperatures or the action of denaturing agents
      (guanidine hydrochloride, urea) have been analyzed. It was shown that the
      terminal phase of aggregation followed, as a rule, first order kinetics. For the
      kinetic curves registered by an increase in the apparent absorbance (A) in time
      (t) the methods of estimation of the corresponding kinetic parameters A(lim) and
      kI (A(lim) is the limiting value of A at t --> infinity and kI is the rate
      constant of the first order) have been proposed. Cases are revealed when the
      reaction rate constant kI calculated from the kinetic curve of aggregation of the
      enzymes coincides with the rate constant for enzyme inactivation. Such a
      situation is interpreted as a case when the rate of aggregation is limited by the
      stage of denaturation of the enzyme. A conclusion has been made that, in order to
      establish the mechanism of protein aggregation, the kinetic investigations of
      aggregation should be carried out over a wide range of protein concentrations.
      The refolding experiments after denaturation of proteins by guanidine
      hydrochloride or urea have been also analyzed. It was shown that aggregation
      accompanying refolding follows first order kinetics at the final phase of the
      process. The model of protein refolding explaining such a kinetic regularity has
      been proposed. When aggregation of protein substrate follows first order
      kinetics, parameters A(lim) and kI may be used for the quantitative
      characterization of the chaperone-like activity in the test-systems based on
      suppression of protein aggregation.

PMID- 11996655
TI  - Isolation of the chromocenter fraction from mouse liver nuclei.
AB  - A new method for isolation of the constitutive heterochromatin (chromocenters)
      from interphase nuclei of mouse liver has been developed. This method allows
      separation of chromocenters of different size. Chromocenter fractions are
      essentially free of nucleoli and other contaminants. In contrast to nuclei and
      nucleoli, the chromocenter fraction is characterized by simpler protein
      composition, this fraction having a reduced number of proteins (especially high
      molecular weight proteins). Chromocenters contain all histone fractions; however,
      the relative proportion of histone H1 is lower and histone H3 is higher than in
      the total nuclear chromatin. The amount of non-histone proteins of 51, 63, 73,
      and 180 kD is higher in the chromocenter fraction than in nuclei and nucleoli.
      The use of immunocytochemistry and immunoblotting methods revealed the presence
      of the specific kinetochore component, CENP A protein. This suggests tight
      association of some molecular kinetochore components with chromocenters in the
      interphase.

PMID- 11996656
TI  - Functional analysis of the Na+/H+ antiporter encoding genes of the cyanobacterium
      Synechocystis PCC 6803.
AB  - The role of putative Na+/H+ antiporters encoded by nhaS1 (slr1727), nhaS3
      (sll0689), nhaS4 (slr1595), and nhaS5 (slr0415) in salt stress response and
      internal pH regulation of the cyanobacterium Synechocystis PCC 6803 was
      investigated. For this purpose the mutants (single, double, and triple) impaired
      in genes coding for Na+/H+ antiporters were constructed using the method of
      interposon mutagenesis. PCR analyses of DNA demonstrated that mutations in nhaS1,
      nhaS4, and nhaS5 genes were segregated completely and the mutants contained only
      inactivated copies of the corresponding genes. Na+/H+ antiporter encoded by nhaS3
      was essential for viability of Synechocystis since no completely segregated
      mutants were obtained. The steady-state intracellular sodium concentration and
      Na+/H+ antiporter activities were found to be the same in the wild type and all
      mutants. No differences were found in the growth rates of wild type and mutants
      during their cultivation in liquid media supplemented with 0.68 M or 0.85 M NaCl
      as well as in media buffered at pH 7.0, 8.0, or 9.0. The expression of genes
      coding for Na+/H+ antiporters was studied. No induction of any Na+/H+ antiporter
      encoding gene expression was found in wild type or single mutant cells grown
      under high salt or at different pH values. Nevertheless, in cells of double and
      triple mutants adapted to high salt or alkaline pH some of the remaining Na+/H+
      antiporter encoding genes showed induction. These results might indicate that
      some of Na+/H+ antiporters can functionally replace each other under stress
      conditions in Synechocystis cells lacking the activity of more than one
      antiporter.

PMID- 11996657
TI  - Effect of modulators of protein kinase C activity on Ca2+ transport in retinal
      rod microsomes.
AB  - The effect of modulators of protein kinase C (PKC) activity on Ca2+ translocation
      in retinal rod microsomes was studied. It is shown that PKC activators (phorbol
      12-myristate-13-acetate (PMA) and diacylglycerol (DAG)) and inhibitors
      (chelerythrine chloride, polymyxin B, and phloretin) stimulate and inhibit ATP
      dependent Ca2+ uptake in retinal rod microsomes, respectively. This effect is
      apparently due to an influence of PKC on Ca-ATPase contained in these vesicular
      structures. It was found that PKC inhibitors (chelerythrine chloride, polymyxin
      B, and phloretin) and activators (PMA and DAG) potentiate Ca2+ release from Ca2+
      loaded retinal rod microsomes. Specific and nonspecific mechanisms of Ca-release
      stimulation by the modulators of PKC activity are discussed.

PMID- 11996658
TI  - Polymerization sites in the D-domain of human fibrin(ogen).
AB  - The present work deals with localization of previously unknown polymerization
      sites of the fibrin DD-fragment. D-dimer we obtained has a pronounced inhibitory
      effect on fibrin polymerization (IC50 = 0.06 microM). The inhibitory effect of
      the DD-fragment disappeared after reduction and carboxymethylation. However,
      polypeptide chains betaDD (Bbeta134-461) and gammagammaDD (gamma63-411)2 of the
      DD-fragment, isolated by preparative electrophoresis, displayed their inhibitory
      activity. For instance, the rates of fibrin protofibril lateral association were
      decreased twice in the presence of betaDD and gammagammaDD chains at their molar
      ratios to fibrin of 0.40 and 0.15, respectively. The IC50 values for betaDD and
      gammagammaDD were 0.24 and 0.10 microM, respectively. Highly specific inhibition
      of protofibril lateral association suggests that the protofibril lateral
      association sites are located in Bbeta134-461 and gamma63-411 regions of the
      fibrin D-domain. Our data confirm those reported by Doolittle et al. regarding
      the gamma-chain and a hypothesis about beta-chain of fibrin D-domain (Yang, Z.,
      Mochalkin, I., and Doolittle, R. F. (2000) Biochemistry, 97, 14156-14161).

PMID- 11996659
TI  - Increase in expression of brain serotonin transporter and monoamine oxidase a
      genes induced by repeated experience of social defeats in male mice.
AB  - Serotonin transporter and monoamine oxidase (MAO) A are involved in the
      inactivation of serotonin. The former is responsible for serotonin re-uptake from
      the synapse, whereas the latter catalyzes serotonin deamination in presynaptic
      terminals. Expression of serotonin transporter and MAO A genes was investigated
      in raphe nuclei of midbrain of CBA/Lac male mice with repeated experience of
      social victories or defeats in 10 daily aggressive confrontations. The amount of
      cDNA of these genes was evaluated using multiplex RT-PCR. Two independent
      experiments revealed that the defeated mice were characterized by significantly
      higher levels of serotonin transporter and MAO A mRNAs than the control and
      aggressive animals. Increased expression of MAO A and serotonin transporter genes
      is suggested to reflect the accelerated serotonin degradation in response to
      activation of the serotonergic system functioning induced by social stress.
      Significant positive correlation between MAO A and serotonin transporter mRNA
      levels suggests common pathways of regulation of transcriptional activity of
      these genes.

PMID- 11996660
TI  - Biotransformation of steroids by a recombinant yeast strain expressing bovine
      cytochrome P-45017alpha.
AB  - The cDNA encoding cytochrome P-45017alpha from bovine adrenal cortex was
      expressed in Saccharomyces cerevisiae under the control of the galactose
      inducible GAL10 promoter. Carbon monoxide difference spectra of the galactose
      induced yeast cells showed expression of about 240 nmol of P-45017alpha per liter
      of the culture. Binding of progesterone to the cytochrome P-45017alpha was
      clearly detectable already with intact yeast cells as judged by the formation of
      type I substrate difference spectra. Yeast cells grown on minimal medium
      containing galactose actively converted progesterone to 17alpha
      hydroxyprogesterone, this indicating the functional integrity of the
      heterologously expressed P-45017alpha and its efficient coupling with the
      constitutive NADPH-cytochrome P-450 reductase. More than 80% of the metabolite
      produced was secreted into the culture medium. Cultivation in a rich non
      selective medium resulted in the formation of an additional product, which was
      identified by mass spectrometry as 17alpha-hydroxy-20-dihydroprogesterone.
      Kinetic analysis revealed that its production followed the cytochrome P
      45017alpha-dependent hydroxylation reaction. The reduction of the 20-keto group
      of 17alpha-hydroxyprogesterone was also observed in the non-induced yeast
      culture, this suggesting the involvement of the constitutive enzyme. Among
      several substrates tested, progesterone was hydroxylated by the cytochrome P
      45017alpha expressed with the highest activity. The activity towards other
      substrates decreased in the sequence: 11beta- > 11alpha- > 19
      hydroxyprogesterone. In conclusion, the present results show that the host-vector
      system used is suitable for high-level functional expression of P-45017alpha and
      further application of enzymatic properties of this protein to perform specific
      steroid biotransformations.

PMID- 11996661
TI  - Thyroxine reversibly inhibits the uncoupling action of protonophores on energy
      production in rat thymus lymphocytes.
AB  - Earlier we reported that some thyroid and steroid hormones and also 6
      ketocholestanol used in micromolar concentrations modulated the effects of
      protonophoric uncouplers on isolated mitochondria (Starkov et al. (1997) Biochim.
      Biophys. Acta, 1318, 173-183). In the present study we investigated the effects
      of a thyroid hormone, thyroxine, on energy coupling of intact rat thymus
      lymphocytes and mitochondria isolated from these cells. The resting (oligomycin
      inhibited) respiration of the isolated intact lymphocytes was stimulated by the
      addition of protonophoric uncouplers 2,4-DNP, FCCP, or SF6847. Subsequent
      addition of micromolar concentrations of thyroxin decreased the rate of uncoupler
      stimulated respiration and partially reversed uncoupler-induced decrease of
      membrane potential (DeltaPsi). In experiments with mitochondria isolated from
      thymus lymphocytes the re-coupling effect of thyroxine was not observed. In this
      case thyroxine did not influence mitochondrial respiration stimulated with 2,4
      DNP, but did potentiate the stimulation of respiration and DeltaPsi decrease
      induced with another uncoupler, SF6847. The data are discussed in terms of a
      hypothesis that aromatic uncouplers are transported into the cell by the
      thyroxine carrier of the plasma membrane.

PMID- 11996662
TI  - Simplest kinetic schemes for biochemical oscillators.
AB  - The topological structure of the simplest critical fragments in biochemical
      systems has been characterized. The conditions are considered where the critical
      fragments induce oscillations of the concentrations of the system participants.
      To illustrate, three biochemical systems (transport of ions through a membrane,
      protein phosphorylation, and two-substrate reaction) are discussed. The kinetic
      schemes of these systems contain one of the discovered critical fragments.
      Relaxation oscillations of the concentrations of the system participants were
      demonstrated using the numerical integration method.

PMID- 11996663
TI  - Vesicular transport of extracellular acid phosphatases in yeast Saccharomyces
      cerevisiae.
AB  - A method for isolation of secretory vesicles from the yeast Saccharomyces
      cerevisiae based on the disintegration of protoplasts by osmotic shock followed
      by separation of the vesicles by centrifugation in a density gradient of
      Urografin was developed in this study. Two populations of the secretory vesicles
      that differ in density and shape were separated. Acid phosphatases (EC 3.1.3.2)
      were used as markers of the secretory vesicles. It was shown that the
      constitutive acid phosphatase (PHO3 gene product) is mainly transported to the
      cell surface by a lower density population of vesicles, while the repressible
      acid phosphatase (a heteromer encoded by PHO5, PHO10, and PHO11 genes) by a
      vesicle population of higher density. These data provide evidence that at least
      two pathways of transport of yeast secretory proteins from the place of their
      synthesis and maturation to the cell surface may exist. To reveal the probable
      reasons for transport of Pho3p and Pho5p/Pho10p/Pho11p enzymes by two different
      kinds of vesicles, we isolated vesicles from strains that synthesize the
      homomeric forms of the repressible acid phosphatase. It was demonstrated that
      glycoproteins encoded by the PHO10 and/or PHO11 genes could be responsible for
      the choice of one of the alternative transport pathways of the repressible acid
      phosphatase. A high correlation coefficient between bud formation and secretion
      of Pho5p phosphatase and the absence of correlation between bud formation and
      secretion of minor phosphatases Pho10p and Pho11p suggests different functional
      roles of the polypeptides that constitute the native repressible acid
      phosphatase.

PMID- 11996664
TI  - Role of Ca2+ in drought stress signaling in wheat seedlings.
AB  - Plants use complex signal transduction pathways to perceive and react to various
      biotic and/or abiotic stresses. As a consequence of this signaling, plants can
      modify their metabolism to adapt themselves to new conditions. One such change is
      the accumulation of proline in response to drought and salinity stresses. We have
      studied drought and salinity induced proline accumulation and the roles of Ca2+
      (10 mM) and indoleacetic acid (IAA, 0.3 mM) in this response. Subjecting
      seedlings to both drought (6% polyethylene glycol, PEG) and salinity (150 mM
      NaCl) stress resulted in a dramatic increase in proline accumulation (7-fold
      higher than control level). However, the application of Ca2+ along with these
      stress factors had different effects. Unlike the salinity stress, Ca2+ prevented
      the drought induced proline accumulation indicating that these stress factors use
      distinct signaling pathways to induce similar responses. Experiments with IAA and
      EGTA (10 mM) supported this interpretation and suggested that Ca2+ and auxin
      participate in signaling mechanisms of drought-induced proline accumulation.
      Drought and salt stress-induced proline accumulation was compared on salt
      resistant (cv. Gerek 79) and salt sensitive (cv. Bezostaya) wheat varieties.
      Although proline level of the first was twofold lower than that of the second in
      control, relative proline accumulation was dramatically higher in the case of the
      salt resistant wheat variety under stress conditions.

PMID- 11996665
TI  - Some properties of site-specific nickase BspD6I and the possibility of its use in
      hybridization analysis of DNA.
AB  - A new method for hybridization analysis of nucleic acids is proposed on the basis
      of the ability of site-specific nickases to cleave only one DNA strand. The
      method is based on the use of a labeled oligonucleotide with the recognition site
      of the nickase hybridized with the target (DNA or RNA) at an optimal temperature
      of the enzyme (55 degrees C). The two shorter oligonucleotides formed after the
      cleavage with the nickase do not complex with the target. Thus, a multiple
      cleavage of the labeled oligonucleotide takes place on one target molecule. The
      cleavage of the nucleotide is recorded either by polyacrylamide gel
      electrophoresis (when a radioactive labeled oligonucleotide is used) or by
      fluorescence measurements (if the oligonucleotide has the structure of a
      molecular beacon). The new method was tested on nickase BspD6I and a radioactive
      oligonucleotide complementary to the polylinker region of the viral DNA strand in
      bacteriophage M13mp19. Unfortunately, nickase BspD6I does not cleave DNA in the
      RNA-DNA duplexes and therefore cannot be used for detection of RNA targets.

PMID- 11996666
TI  - Interaction between tubulin and Na+,K+-ATPase in brain stem neurons.
AB  - Functionally active Na+,K+-ATPase isozymes containing three types of the
      catalytic subunits (alpha1, alpha2, and alpha3) were obtained from calf brain by
      two methods: selective removal of contaminating proteins according to Jorgensen
      (1974) and selective solubilization of the enzyme with subsequent reformation of
      the membrane structure according to Esmann (1988). All preparations were
      characterized with respect to ouabain-inhibition constants. The presence of the
      cytoskeleton protein tubulin (beta3 isoform) in the high-molecular-weight complex
      of Na+,K+-ATPase alpha3beta1 isozyme from brain stem axolemma and the junction
      between Na+,K+-ATPase alpha3 subunit and tubulin beta3 subunit are shown for the
      first time.

PMID- 11996667
TI  - Tumour necrosis factor-induced activation of c-Jun N-terminal kinase is sensitive
      to caspase-dependent modulation while activation of mitogen-activated protein
      kinase (MAPK) or p38 MAPK is not.
AB  - The activation of the extracellular signal-regulated kinases (ERKs) by tumour
      necrosis factor-alpha (TNF) receptors (TNFRs) is an integral part of the
      cytokine's pleiotropic cellular responses. Here we report differences in the
      caspase sensitivity and TNFR subtype activation of members of the ERK family.
      Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the
      expression of CrmA (cytokine response modifier A), a viral modifier protein,
      blocks TNF-induced apoptosis or caspase-dependent protein kinase Cdelta and
      poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun
      N-terminal kinase (JNK) activity was attenuated in cells in which caspase
      activity was inhibited either by pharmacological blockers or CrmA expression.
      Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however,
      only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase
      (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK
      activities were insensitive to pharmacological caspase inhibition or CrmA. These
      findings were supported when measuring TNF-induced cytosolic phospholipase A(2)
      activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase
      enzymes activated by TNF in HeLa cells showed sequential caspase-8, -3, -7, -6
      and -9 activation, with their inhibition characteristics suggesting a role for
      caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these
      results show delineated ERK-activation pathways employed by TNFR subtypes.

PMID- 11996668
TI  - A peptide mimic of an antigenic loop of alpha-human chorionic gonadotropin
      hormone: solution structure and interaction with a llama V(HH) domain.
AB  - The X-ray structure of a ternary complex between human chorionic gonadotropin
      hormone (hCG) and two Fvs recognizing its alpha and beta subunits has been
      recently determined. The Fvs recognize the elongated hCG molecule by its two
      ends, one being the Leu-12-Cys-29 loop of the alpha subunit. We have designed and
      synthesized a 17-amino-acid peptide (named PepH14) derived from the sequence of
      this antigenic loop with the purpose of mimicking its three-dimensional structure
      and its affinity for antibodies. We have determined the solution structure of
      PepH14 by homonuclear NMR spectroscopy and derived distance restraints.
      Comparison of this structure with that of the corresponding antigenic loop of
      alpha-hCG reveals strong conformational similarities. In particular, the two
      pairs of residues that establish crucial contacts with the Fv fragment share the
      same conformation in PepH14 and in the authentic hormone loop. We propose a three
      dimensional model of interaction of PepH14 with a llama V(HH) (V(HH)-H14)
      fragment cloned from a single-chain llama immunoglobulin raised against alpha
      hCG. This model has been constrained by the chemical shift variations of the H14
      1HN and 15N resonances monitored upon binding with PepH14. Mapping of the
      backbone chemical shift variations on the V(HH) structure determined by NMR
      indicates that PepH14 binds to V(HH)-H14 and forms a complex using the three
      complementary determining regions (CDRs). They define a shallow groove
      encompassing residues Thr-31, Ala-56, Tyr-59 and Trp-104 which have been shown to
      be in conformational exchange [Renisio, Perez, Czisch, Guenneugues, Bornet,
      Frenken, Cambillau and Darbon (2002) Proteins 47, 546-555] and also Phe-37 and
      Ala-50. This groove is close to the hydrophobic interface area observed between
      VH and VL domains in Fvs from classical antibodies, which explains the rather
      lateral binding of PepH14 on the V(HH).

PMID- 11996669
TI  - Severe pyridine nucleotide depletion in fibroblasts from Lesch-Nyhan patients.
AB  - The relationship between a complete deficiency of the purine enzyme hypoxanthine
      guanine phosphoribosyltransferase and the neurobehavioural abnormalities in Lesch
      Nyhan disease remains an enigma. In vitro studies using lymphoblasts or
      fibroblasts have evaluated purine and pyrimidine metabolism with conflicting
      results. This study focused on pyridine nucleotide metabolism in control and
      Lesch-Nyhan fibroblasts using radiolabelled salvage precursors to couple the
      extent of uptake with endocellular nucleotide concentrations. The novel finding,
      highlighted by specific culture conditions, was a marked NAD depletion in Lesch
      Nyhan fibroblasts. ATP and GTP were also 50% of the control, as reported in
      lymphoblasts. A 6-fold greater incorporation of [(14)C]nicotinic acid into
      nicotinic acid- adenine dinucleotide by Lesch-Nyhan fibroblasts, with no
      unmetabolized substrate (20% in controls), supported disturbed pyridine
      metabolism, NAD depletion being related to utilization by poly(ADP-ribose)
      polymerase in DNA repair. Although pyrimidine nucleotide concentrations were
      similar to controls, Lesch-Nyhan cells showed reduced [(14)C]cytidine/uridine
      salvage into UDP sugars. Incorporation of [(14)C]uridine into CTP by both was
      minimal, with more than 50% [(14)C]cytidine metabolized to UTP, indicating that
      fibroblasts, unlike lymphoblasts, lack active CTP synthetase, but possess
      cytidine deaminase. Restricted culture conditions may be neccesary to mimic the
      situation in human brain cells at an early developmental stage. Cell type may be
      equally important. NAD plus ATP depletion in developing brain could restrict DNA
      repair, leading to neuronal damage/loss by apoptosis, and, with GTP depletion,
      affect neurotransmitter synthesis and basal ganglia dopaminergic neuronal
      systems. Thus aberrant pyridine nucleotide metabolism could play a vital role in
      the pathophysiology of Lesch-Nyhan disease.

PMID- 11996670
TI  - The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor
      interacts with 14-3-3 proteins.
AB  - The Protein 4.1 family contains at least two members that function as tumour
      suppressors, the neurofibromatosis 2 gene product merlin and the recently
      identified differentially expressed in adenocarcinoma of the lung (DAL-1)/Protein
      4.1B molecule. DAL-1/Protein 4.1B loss is observed in a variety of tumours,
      including breast and lung cancers as well as meningiomas. We have previously
      demonstrated that DAL-1/Protein 4.1B interacts with some but not all merlin
      binding proteins, raising the possibility that DAL-1/Protein 4.1B associates with
      additional unique proteins specific to its function as a negative growth
      regulator. Using yeast two-hybrid interaction cloning, we identified three 14-3-3
      isoforms, beta, gamma and eta, to be DAL-1/Protein 4.1B-binding proteins. These
      interactions were verified by using glutathione S-transferase affinity
      chromatography in vitro and co-immunoprecipitation in vivo. The interaction of 14
      3-3 with DAL-1/Protein 4.1B was specific, as 14-3-3 did not bind to the related
      Protein 4.1 family members merlin, ezrin or radixin. The DAL-1/Protein 4.1B
      domain that mediates 14-3-3 binding was mapped to residues Pro(244) and Leu(280)
      within the 4.1/ezrin/radixin/moesin domain. The identification of this novel DAL
      1/Protein 4.1B-interacting protein represents the first step towards elucidating
      its potentially unique mechanism of action.

PMID- 11996671
TI  - Size is a major determinant of dissociation and denaturation behaviour of
      reconstituted high-density lipoproteins.
AB  - Lipid-free apolipoprotein A-I (apoA-I) and A-I(Milano) (A-I(M)) were compared for
      their denaturation behaviour by running across transverse gradients of a
      chaotrope, urea, and of a ionic detergent, SDS. For both apo A-I and monomeric
      apoA-I(M) in the presence of increasing concentrations of urea the transition
      from high to low mobility had a sigmoidal course, whereas for dimeric A-I(M)/A
      I(M) a non-sigmoidal shape was observed. The co-operativity of the unfolding
      process was lower for dimeric A-I(M)/A-I(M) than for apoA-I or for monomeric apoA
      I(M). A slightly higher susceptibility to denaturation was observed for dimeric A
      I(M)/A-I(M) than for monomeric apoA-I(M). A similar behaviour of A-I(M)/A-IM
      versus apoA-I(M) was observed in CD experiments. Large- (12.7/12.5 nm) and small-
      (7.8 nm) sized reconstituted high-density lipoproteins (rHDL) containing either
      apoA-I or A-I(M)/A-I(M) were compared with respect to their protein-lipid
      dissociation behaviour by subjecting them to electrophoresis in the presence of
      urea, of SDS and of a non-ionic detergent, Nonidet P40. A higher susceptibility
      to dissociation of small-sized versus large-sized rHDL, regardless of the
      apolipoprotein component, was observed in all three instances. Our data
      demonstrate that the differential plasticity of the various classes of rHDL is a
      function of their size; the higher stability of 12.5/12.7 nm rHDL is likely
      connected to the higher number of protein-lipid and lipid-lipid interactions in
      larger as compared with smaller rHDL.

PMID- 11996672
TI  - Fuc(alpha1-->3)GalNAc-: the major antigenic motif of Schistosoma mansoni
      glycolipids implicated in infection sera and keyhole-limpet haemocyanin cross
      reactivity.
AB  - The aim of the present study was the characterization of the dominant epitope
      present on Schistosoma mansoni glycolipids, which causes cross-reactivity of S.
      mansoni and S. haematobium infection sera with keyhole-limpet haemocyanin (KLH).
      To this end, the monoclonal antibody M2D3H was chosen for its similar behaviour
      in high-performance TLC immunostaining and inhibition-ELISA to infection sera.
      Individual, structurally defined oligosaccharides derived from S. mansoni egg
      glycolipids were tested for their binding to this monoclonal antibody by
      immunoaffinity chromatography. A terminal fucose residue linked in the (alpha1-
      >3) position to N-acetylgalactosamine was found to be the common structural
      determinant of the four oligosaccharides binding to M2D3H. The Fuc(alpha1-
      >3)GalNAc-motif also appeared to be the basis for the cross-reactivity with KLH,
      a phenomenon used in the serodiagnosis of S. mansoni, S. haematobium and S.
      japonicum infections.

PMID- 11996673
TI  - Statistics on continuous IBD data: exact distribution evaluation for a pair of
      full(half)-sibs and a pair of a (great-) grandchild with a (great-) grandparent.
AB  - BACKGROUND: Pairs of related individuals are widely used in linkage analysis.
      Most of the tests for linkage analysis are based on statistics associated with
      identity by descent (IBD) data. The current biotechnology provides data on very
      densely packed loci, and therefore, it may provide almost continuous IBD data for
      pairs of closely related individuals. Therefore, the distribution theory for
      statistics on continuous IBD data is of interest. In particular, distributional
      results which allow the evaluation of p-values for relevant tests are of
      importance. RESULTS: A technology is provided for numerical evaluation, with any
      given accuracy, of the cumulative probabilities of some statistics on continuous
      genome data for pairs of closely related individuals. In the case of a pair of
      full-sibs, the following statistics are considered: (i) the proportion of genome
      with 2 (at least 1) haplotypes shared identical-by-descent (IBD) on a chromosomal
      segment, (ii) the number of distinct pieces (subsegments) of a chromosomal
      segment, on each of which exactly 2 (at least 1) haplotypes are shared IBD. The
      natural counterparts of these statistics for the other relationships are also
      considered. Relevant Maple codes are provided for a rapid evaluation of the
      cumulative probabilities of such statistics. The genomic continuum model, with
      Haldane's model for the crossover process, is assumed. CONCLUSIONS: A technology,
      together with relevant software codes for its automated implementation, are
      provided for exact evaluation of the distributions of relevant statistics
      associated with continuous genome data on closely related individuals.

PMID- 11996674
TI  - Craniodental variation among Macaques (Macaca), nonhuman primates.
AB  - BACKGROUND: In terms of structure and function, the skull is one of the most
      complicated organs in the body. It is also one of the most important parts in
      terms of developmental and evolutionary origins. This complexity makes it
      difficult to obtain evolutionary assessments if, as is usually the case with
      fossils, only part of the skull is available. For this reason this study involves
      a set of comparisons whereby the smallest functional units are studied first, and
      these built up, through a triple-nested hierarchical design, into more complex
      anatomical regions and eventually into the skull-as-a-whole. This design has been
      applied to macaques (Macaca) in order to reveal patterns of variation at the
      different levels. The profiles of such variation have been obtained both within
      and between species. This has lead to a search for the skull parts that have
      undergone similar selection pressures during evolution and comparable development
      patterns in both ontogeny and phylogeny. RESULTS: Morphometric analysis
      (Principal Components) was used to obtain these profiles of species and sex
      separations based on 77 cranial variables from 11 species of macaques. The
      results showed that 7 functional units could be aggregated into three
      functionally reasonable anatomical regions on the basis of similarities in
      profiles. These were: the masticatory apparatus containing mandible, lower teeth
      and upper teeth, the face as a whole combining maxilla (actually lower face) and
      upper face, and the cranium as a whole involving cranium and calvaria. Twenty-six
      variables were finally selected for analyzing the morphology of the whole skull.
      This last showed an overall profile similar to that revealed in the masticatory
      apparatus but also contained additional information pertaining to individual
      species and species-groups separations. CONCLUSIONS: The study provides a model
      for carrying out analysis of species separations and sex variation
      simultaneously. Through this design it seems possible to see cranio-dental
      elements that may result from similar developmental processes, have similar
      functional adaptations, and show an appropriately integrated structure
      morphologically. This study also implies that the biological information drawn
      from part of skull alone, e.g. as in studies of incomplete fossils may provide
      misleading information.

PMID- 11996675
TI  - Hisactophilin is involved in osmoprotection in Dictyostelium.
AB  - BACKGROUND: Dictyostelium cells exhibit an unusual stress response as they
      protect themselves against hyperosmotic stress. Cytoskeletal proteins are
      recruited from the cytosolic pool to the cell cortex, thereby reinforcing it. In
      order to gain more insight into the osmoprotective mechanisms of this amoeba, we
      used 1-D and 2-D gel electrophoresis to identify new proteins that are
      translocated during osmotic shock. RESULTS: We identified hisactophilin as one of
      the proteins that are enriched in the cytoskeletal fraction during osmotic shock.
      In mutants lacking hisactophilin, viability is reduced under hyperosmotic stress
      conditions. In wild type cells, serine phosphorylation of hisactophilin was
      specifically induced by hypertonicity, but not when other stress conditions were
      imposed on cells. The phosphorylation kinetics reveals a slow accumulation of
      phosphorylated hisactophilin from 20-60 min after onset of the hyperosmotic shock
      condition. CONCLUSION: In the present study, we identified hisactophilin as an
      essential protein for the osmoprotection of Dictyostelium cells. The observed
      phosphorylation kinetics suggest that hisactophilin regulation is involved in
      long-term osmoprotection and that phosphorylation occurs in parallel with
      inactivation of the dynamic actin cytoskeleton.

PMID- 11996676
TI  - Mobilization of seed storage lipid by Arabidopsis seedlings is retarded in the
      presence of exogenous sugars.
AB  - BACKGROUND: Soluble sugar levels must be closely regulated in germinating seeds
      to ensure an adequate supply of energy and building materials for the developing
      seedling. Studies on germinating cereal seeds indicate that production of sugars
      from starch is inhibited by increasing sugar levels. Although numerous studies
      have focused on the regulation of starch metabolism, very few studies have
      addressed the control of storage lipid metabolism by germinating oilseeds.
      RESULTS: Mobilization of storage lipid by germinating seeds of the model oilseed
      plant Arabidopsis thaliana (L.) Heynh. occurs at a greatly reduced rate in the
      presence of exogenous glucose or mannose, but not in the presence of equi-molar 3
      O-methylglucose or sorbitol. The sugar-insensitive5-1/abscisic acid-insensitive4
      101 (sis5-1/abi4-101) mutant is resistant to glucose inhibition of seed storage
      lipid mobilization. Wild-type seedlings become insensitive to glucose inhibition
      of storage lipid breakdown within 3 days of the start of imbibition. CONCLUSIONS:
      Growth in the presence of exogenous glucose significantly retards mobilization of
      seed storage lipid in germinating seeds from wild-type Arabidopsis. This effect
      is not solely due to the osmotic potential of the media, as substantially higher
      concentrations of sorbitol than of glucose are required to exert significant
      effects on lipid breakdown. The inhibitory effect of glucose on lipid breakdown
      is limited to a narrow developmental window, suggesting that completion of some
      critical metabolic transition results in loss of sensitivity to the inhibitory
      effect of glucose on lipid breakdown.

PMID- 11996678
TI  - Epidemiology of urban canine rabies, Santa Cruz, Bolivia, 1972-1997.
AB  - We analyzed laboratory data from 1972 to 1997 from Santa Cruz, Bolivia, to
      determine risk factors for laboratory canine samples' testing positive for Rabies
      virus (RABV). Of 9,803 samples, 50.7% tested positive for RABV; the number of
      cases and the percentage positive has dropped significantly since 1978. A 5- to 6
      year cycle in rabies incidence was clearly apparent, though no seasonality was
      noted. Male dogs had significantly increased odds of testing positive for RABV
      (odds ratio [OR]=1.14), as did 1- to 2-year-old dogs (OR=1.73); younger and older
      dogs were at lower risk. Samples submitted from the poorer suburbs of the city
      were more likely to test positive for RABV (OR=1.71). Knowledge of the
      distribution of endemic canine rabies in an urban area will help focus control
      measures in a resource-poor environment.

PMID- 11996677
TI  - Risk to human health from a plethora of simian immunodeficiency viruses in
      primate bushmeat.
AB  - To assess human exposure to Simian immunodeficiency virus (SIV) in west central
      Africa, we looked for SIV infection in 788 monkeys that were hunted in the
      rainforests of Cameroon for bushmeat or kept as pets. Serologic reactivity
      suggesting SIV infection was found in 13 of 16 primate species, including 4 not
      previously known to harbor SIV. Overall, 131 sera (16.6%) reacted strongly and an
      additional 34 (4.3%) reacted weakly with HIV antigens. Molecular analysis
      identified five new phylogenetic SIV lineages. These data document for the first
      time that a substantial proportion of wild monkeys in Cameroon are SIV infected
      and that humans who hunt and handle bushmeat are exposed to a plethora of
      genetically highly divergent viruses.

PMID- 11996679
TI  - Clonal groupings in serogroup X Neisseria meningitidis.
AB  - The genetic diversity of 134 serogroup X Neisseria meningitis isolates from
      Africa, Europe, and North America was analyzed by multilocus sequence typing and
      pulsed-field gel electrophoresis. Although most European and American isolates
      were highly diverse, one clonal grouping was identified in sporadic disease and
      carrier strains isolated over the last 2 decades in the United Kingdom, the
      Netherlands, Germany, and the United States. In contrast to the diversity in the
      European and American isolates, most carrier and disease isolates recovered
      during the last 30 years in countries in the African meningitis belt belonged to
      a second clonal grouping. During the last decade, these bacteria have caused
      meningitis outbreaks in Niger and Ghana. These results support the development of
      a comprehensive conjugate vaccine that would include serogroup X polysaccharide.

PMID- 11996680
TI  - Genetic variants of Ehrlichia phagocytophila, Rhode Island and Connecticut.
AB  - Primers were used to amplify a 561-bp region of the 16S rRNA gene of Ehrlichia
      phagocytophila from Ixodes scapularis ticks and small mammals collected in Rhode
      Island and Connecticut. DNA sequences for all 50 E. phagocytophila-positive
      samples collected from 1996 through 1998 in southwestern Connecticut were
      identical to the sequence reported for E. phagocytophila DNA from confirmed human
      cases. In contrast, the sequences from 92 of 123 E. phagocytophila-positive Rhode
      Island samples collected from 1996 through 1999 included several variants
      differing by 1-2 nucleotides from that in the agent infecting humans. While 11.9%
      of 67 E. phagocytophila-positive ticks collected during 1997 in Rhode Island
      harbored ehrlichiae with sequences identical to that of the human agent, 79.1%
      had a variant sequence not previously described. The low incidence of human
      ehrlichiosis in Rhode Island may in part result from interference by these
      variant ehrlichiae with maintenance and transmission of the true agent of human
      disease.

PMID- 11996681
TI  - Trends in fluoroquinolone (ciprofloxacin) resistance in enterobacteriaceae from
      bacteremias, England and Wales, 1990-1999.
AB  - The Public Health Laboratory Service receives antibiotic susceptibility data for
      bacteria from bloodstream infections from most hospitals in England and Wales.
      These data were used to ascertain resistance trends to ciprofloxacin from 1990
      through 1999 for the most prevalent gram-negative agents: Escherichia coli,
      Klebsiella spp., Enterobacter spp., and Proteus mirabilis. Significant increases
      in resistance were observed for all four species groups. For E. coli,
      ciprofloxacin resistance rose from 0.8% in 1990 to 3.7% in 1999 and became widely
      scattered among reporting hospitals. The prevalence of resistance in Klebsiella
      spp. rose from 3.5% in 1990, to 9.5% in 1996 and 7.1% in 1999, while that in
      Enterobacter spp. rose from 2.1% in 1990 to 10.5% in 1996 and 10.9% in 1999. For
      both Klebsiella and Enterobacter spp., most resistance was localized in a few
      centers. Resistance was infrequent and scattered in P. mirabilis, but reached a
      prevalence of 3.3% in 1999.

PMID- 11996682
TI  - Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children:
      implications for the use of heptavalent pneumococcal conjugate vaccine.
AB  - We assessed the prevalence of Streptococcus pneumoniae serotypes in the
      nasopharynx of healthy children, antimicrobial susceptibility patterns, risk
      factors for carriage, and the coverage of heptavalent pneumococcal conjugate
      vaccine. In 2,799 healthy infants and children, the S. pneumoniae carrier rate
      was 8.6% (serotypes 3, 19F, 23F, 19A, 6B, and 14 were most common). Most
      pneumococci (69.4%) were resistant to one or more antimicrobial classes. The rate
      of penicillin resistance was low (9.1%); macrolide resistance was high (52.1%).
      Overall, 63.2% of the isolates belonged to strains covered by the heptavalent
      pneumococcal vaccine. This percentage was higher in children <2 years old (73.1%)
      and in those ages 2-5 years (68.9%). Sinusitis in the previous 3 months was the
      only risk factor for carrier status; acute otitis media was the only risk factor
      for the carriage of penicillin-resistant S. pneumoniae. Most isolated strains are
      covered by the heptavalent conjugate vaccine, especially in the first years of
      life, suggesting that its use could reduce the incidence of pneumococcal disease.

PMID- 11996683
TI  - Hospital-based diagnosis of hemorrhagic fever, encephalitis, and hepatitis in
      Cambodian children.
AB  - Surveillance was conducted for three clinical syndromes (hemorrhagic fever,
      encephalitis, and hepatitis) in Cambodian children admitted to the National
      Pediatric Hospital in Phnom Penh from July 1996 through September 1998. Acute-
      and convalescent-phase sera, and cerebrospinal fluid, when applicable, underwent
      diagnostic evaluation for infections with Dengue virus (DENV), Japanese
      encephalitis virus (JEV), and Hepatitis A, B, C, and E viruses. Of 621 children
      admitted with hemorrhagic fever, 499 (80%) were confirmed to have either primary
      or secondary DENV infection. DENV rates were as high as 10.6/100 hospital
      admissions in September 1998. Of 50 children with clinical encephalitis, 9 (18%)
      had serologic evidence of JEV infection. Forty-four children had clinical
      hepatitis, most (55%) due to Hepatitis A virus (HAV). One patient had Hepatitis B
      virus, and no patients had hepatitis C or E. This study identified a large number
      of children with vaccine-preventable diseases (JEV and HAV).

PMID- 11996684
TI  - Excess mortality associated with antimicrobial drug-resistant Salmonella
      typhimurium.
AB  - In a matched cohort study, we determined the death rates associated with drug
      resistance in Salmonella Typhimurium. We linked data from the Danish Surveillance
      Registry for Enteric Pathogens with the Civil Registration System and the Danish
      National Discharge Registry. By survival analysis, the 2-year death rates were
      compared with a matched sample of the general Danish population, after the data
      were adjusted for differences in comorbidity. In 2,047 patients with S.
      Typhimurium, 59 deaths were identified. Patients with pansusceptible strains of
      S. Typhimurium were 2.3 times more likely to die 2 years after infection than
      persons in the general Danish population. Patients infected with strains
      resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, and
      tetracycline were 4.8 times (95% CI 2.2 to 10.2) more likely to die, whereas
      quinolone resistance was associated with a mortality rate 10.3 times higher than
      the general population.

PMID- 11996685
TI  - Sentinel surveillance: a reliable way to track antibiotic resistance in
      communities?
AB  - We used population-based data to evaluate how often groups of randomly selected
      clinical laboratories accurately estimated the prevalence of resistant
      pneumococci and captured trends in resistance over time. Surveillance for
      invasive pneumococcal disease was conducted in eight states from 1996 to 1998.
      Within each surveillance area, we evaluated the proportion of all groups of
      three, four, and five laboratories that estimated the prevalence of penicillin
      nonsusceptible pneumococci (%PNSP) and the change in %PNSP over time. We assessed
      whether sentinel groups detected emerging fluoroquinolone resistance. Groups of
      five performed best. Sentinel groups accurately predicted %PNSP in five states;
      states where they performed poorly had high between-laboratory variation in
      %PNSP. Sentinel groups detected large changes in prevalence of nonsusceptibility
      over time but rarely detected emerging fluoroquinolone resistance.
      Characteristics of hospital-affiliated laboratories were not useful predictors of
      a laboratory's %PNSP. Sentinel surveillance for resistant pneumococci can detect
      important trends over time but rarely detects newly emerging resistance profiles.

PMID- 11996686
TI  - Evaluation in nonhuman primates of vaccines against Ebola virus.
AB  - Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of
      cases in both humans and nonhuman primates. No vaccines or treatments are
      available for human use. We evaluated the effects in nonhuman primates of vaccine
      strategies that had protected mice or guinea pigs from lethal EBOV infection. The
      following immunogens were used: RNA replicon particles derived from an attenuated
      strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV
      glycoprotein and nucleoprotein; recombinant Vaccinia virus expressing EBOV
      glycoprotein; liposomes containing lipid A and inactivated EBOV; and a
      concentrated, inactivated whole-virion preparation. None of these strategies
      successfully protected nonhuman primates from robust challenge with EBOV. The
      disease observed in primates differed from that in rodents, suggesting that
      rodent models of EBOV may not predict the efficacy of candidate vaccines in
      primates and that protection of primates may require different mechanisms.

PMID- 11996687
TI  - Typical and atypical enteropathogenic Escherichia coli.
AB  - Typical and atypical enteropathogenic Escherichia coli (EPEC) strains differ in
      several characteristics. Typical EPEC, a leading cause of infantile diarrhea in
      developing countries, is rare in industrialized countries, where atypical EPEC
      seems to be a more important cause of diarrhea. For typical EPEC, the only
      reservoir is humans; for atypical EPEC, both animals and humans can be
      reservoirs. Typical and atypical EPEC also differ in genetic characteristics,
      serotypes, and virulence properties. Atypical EPEC is more closely related to
      Shiga toxin-producing E. coli (STEC), and like STEC these strains appear to be
      emerging pathogens.

PMID- 11996688
TI  - Increasing quinolone resistance in Salmonella enterica serotype Enteritidis.
AB  - Until recently, Salmonella enterica serotype Enteritidis has remained sensitive
      to most antibiotics. However, national surveillance data from Denmark show that
      quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in
      2000. These data support concerns that the current use of quinolone in food
      animals leads to increasing resistance in S. Enteritidis and that action should
      be taken to limit such use.

PMID- 11996689
TI  - Molecular characterization of Corynebacterium diphtheriae isolates, Russia, 1957
      1987.
AB  - In the 1990s, the Newly Independent and Baltic States of the former Soviet Union
      experienced the largest diphtheria outbreak since the 1960s; it was caused by
      Corynebacterium diphtheriae strains of a unique clonal group. To address its
      origin, we studied 47 clinical isolates from Russia and demonstrated that this
      clonal group was an integral part of the endemic reservoir that existed in Russia
      at least 5 years before the epidemic began.

PMID- 11996690
TI  - Outbreak of Neisseria meningitidis, Edmonton, Alberta, Canada.
AB  - From December 1999 to April 2001, the greater Edmonton region had 61 cases of
      invasive meningococcal infection, two fatal. The outbreak was due to Neisseria
      meningitidis serogroup C, electrophoretic type 15, serotype 2a. Analysis of the
      strains showed that 50 of 56 culture-confirmed cases were due to a single clone
      and close relatives of this clone. This strain had not been previously identified
      in the province of Alberta dating back to January 1997.

PMID- 11996691
TI  - Cefepime MIC as a predictor of the extended-spectrum beta-lactamase type in
      Klebsiella pneumoniae, Taiwan.
AB  - To guide selection of carbapenems or fourth-generation cephalosporins as therapy,
      110 Klebsiella pneumoniae isolates with extended-spectrum beta-lactamases from
      Taiwan were characterized by phenotypic (MICs), molecular, and chemical methods.
      MIC patterns of ceftazidime and cefepime clearly differentiate strains treatable
      by cefepime and those capable of efficiently hydrolyzing available cephalosporins
      (CTX-M series and SHV-types). Continued use of cefepime appears to be a treatment
      option in cases for which MIC results are available and interpreted by the
      criteria presented.

PMID- 11996692
TI  - Deer meat as the source for a sporadic case of Escherichia coli O157:H7
      infection, Connecticut.
AB  - We report a case of Escherichia coli O157:H7, which was acquired by eating wild
      White-Tailed deer (Odocoileus virginianus). DNA fingerprint analysis verified
      venison as the source of infection. This pediatric case emphasizes the need for
      dissemination of information to hunters regarding the safe handling and
      processing of venison.

PMID- 11996693
TI  - Phylogenetic analysis of a human isolate from the 2000 Israel West Nile virus
      epidemic.
AB  - Specimens from a patient of the 2000 Israel West Nile virus epidemic were
      analyzed by reverse transcription-polymerase chain reaction. Products
      corresponding to E, NS3, and NS5 sequences were amplified from cerebellar but not
      from cortical samples. Phylogenetic analyses indicated a closer relationship of
      this isolate to 1996 Romanian and 1999 Russian than to 1998-99 Israeli or 1999
      New York isolates.

PMID- 11996694
TI  - Knowledge of bat rabies and human exposure among United States cavers.
AB  - We surveyed cavers who attended the National Speleological Society convention in
      June 2000. Fifteen percent of respondents did not consider a bat bite a risk for
      acquiring rabies; only 20% had received preexposure prophylaxis against the
      disease. An under-appreciation of the risk for rabies from bat bites may explain
      the preponderance of human rabies viruses caused by variant strains associated
      with bats in the United States.

PMID- 11996695
TI  - First Shiga toxin-producing Escherichia coli isolate from a patient with
      hemolytic uremic syndrome, Brazil.

PMID- 11996696
TI  - Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece.

PMID- 11996697
TI  - [Crazy cows and human prion diseases].

PMID- 11996698
TI  - [Diagnosis of human brucellosis. Role of pH in the seroagglutination test and
      influence of pH on the agglutinating activity of IgM, IgG and IgA antibodies].
AB  - OBJECTIVE: To evaluate the role of pH in the seroagglutination test (SAT)and Rose
      Bengal (RB) test, and to determine the influence of pH on the agglutinating
      activity of IgM, IgG and IgA antibodies. MATERIALS AND METHODS: The SAT was
      performed at pH 7.2 or pH 5.0 in standard microtiter-type polystyrene plates
      using Ring Test antigen or the Brucella suspension (BRUCAPT) provided in the
      Brucellacapt kits. Specific antibodies against native hapten were determined by
      radial immunodiffusion. Additionally, IgG, IgA and IgM fractions were separated
      from 8 sera by absorption chromatography and their agglutinating capacity was
      studied at pH 7.2 and 5.0. RESULTS: We studied 72 sera from patients with
      clinical brucellosis taken at the time of hospitalization, 16 from persons in
      contact with infected animals, and 16 from healthy donors. SAT results at pH 5.0
      correlated with those obtained with the Rose Bengal test. Four Rose Bengal
      positive sera were found to be SAT-negative at pH 7.2 and SAT-positive at pH 5.0.
      SAT performed at pH 5.0 with BRUCAPT antigen yielded higher titers than tests
      performed at pH 7.2 or 5.0 with Ring Test antigen (p < 0.001), with highest
      titers in IDR-positive sera. Among the 8 IgG fractions, all but one agglutinated
      at pH 7.2, and in 4, IgG titers showed significant increases at pH 5.0. Three IgA
      fractions were SAT-negative at pH 7.2 and SAT-positive at pH 5.0; the other 5
      agglutinated at both pH conditions and were DTT-sensitive. All IgA fractions but
      one were positive by Rose Bengal. Agglutinating activity of the IgM fraction was
      not affected by pH. CONCLUSION: The SAT performed with the buffer and antigen
      suspension included in the Brucellacapt kit (pH 5.0) is highly useful for
      detecting agglutinating and non-agglutinating antibodies at pH 7.2.

PMID- 11996699
TI  - [Evaluation of an applied program for the prevention and control of
      tuberculosis].
AB  - BACKGROUND: To evaluate the efficacy of a tuberculosis prevention and control
      program applied in the health care area of Cadiz (Spain). MATERIALS AND METHODS:
      Tuberculosis cases diagnosed by microbiological criteria (Ziehl-Neelsen/auramine
      smear and/or culture in Lowenstein-Jensen medium) from 1996 to 2000 were analyzed
      in relation to epidemiologic characteristics of the patients. Susceptibility
      studies were performed from 1997 onwards using the proportion method described by
      Canetti, Rist and Grosset. RESULTS: The rate of tuberculous infections gradually
      dropped from 38.4 cases/100,000 inhabitants in 1996 to 16.0 cases/100,000
      inhabitants in 2000. Along the study period, the percentage of men affected by
      the disease ranged from 81.2% in 1996 to 70.0% in 2000. In 1996, 26.0% of
      tuberculous patients were HIV-positive, and in 2000, 27.5%. The sensitivity of
      microbiologic diagnosis increased considerably from 60.4% in 1996 to 67.5% in
      2000. Multi-drug resistance (9.2% en 1997) has virtually disappeared in our area
      since 1998 (1.6%).CONCLUSIONS. Implementation of a plan for the prevention and
      control of tuberculosis in our geographic area was effective, resulting in a
      decrease in the infection rate to less than 25 cases/100,000 inhabitants, and
      improvements in microbiologic diagnosis and compliance with treatment.
      Tuberculous disease has affected an increasingly higher proportion of women,
      regardless of HIV status. Antimicrobial resistance, particularly multi-drug
      resistance is now low in our area.

PMID- 11996700
TI  - [HIV infection and other sexually-transmitted infections among immigrants in
      Barcelona].
AB  - BACKGROUND: Immigration is a recent phenomenon in Spain. Certain subgroups of the
      immigrant population may be vulnerable to acquiring sexually transmitted
      infections (STI). MATERIAL AND METHODS: Descriptive study of the seroprevalenceof
      certain STI (HIV, hepatitis B and syphilis) and the general characteristicsn of
      persons tested for HIV infection in a specialized clinic in Barcelona during the
      year 2000. RESULTS: Seroprevalence of HIV was similar in immigrants and native
      residents(1.8% vs. 1.7% respectively). However, the seroprevalences of hepatitis
      B virus (anti-HBc) (19.5% vs. 8.3%) and syphilis (RPR 1 TPHA) (3.2% vs. 1.1%), as
      well as other STI and the practice of prostitution, were higher in immigrants.
      CONCLUSIONS: Several STI, including hepatitis B and syphilis, were found more
      frequently in immigrants than in the native population, whereas HIV
      seroprevalence was similar in the two groups.

PMID- 11996701
TI  - [Evolution of the sensitivity of 235 strains of Helicobacter pylori from 1995 to
      1998 and impact of antibiotic treatment].
AB  - BACKGROUND: The aim of this study was to investigate the sensitivity of
      Helicobacter pylori to the antibiotics used in its eradication over a period of
      four years and to determine the influence of previous treatment on sensitivity.
      MATERIAL AND METHODS: During the period from 1995 to 1998 we determined the
      sensitivity of 235 consecutive Helicobacter pylori isolates to amoxicillin,
      metronidazole, clarythromycin and tetracycline by means of E-test methodology.
      The MIC values found were related with the prior use of eradicating treatment.
      RESULTS: The percentage of resistant strains were as follows: 23.5% to
      metronidazole, 12.9% to clarythromycin and 0.7% to tetracycline; none of the
      strains was resistant to amoxicillin. There were no significant changes in
      percentage of resistance to the drugs studied over the 4-year period. Resistance
      to metronidazole and clarythromycin was significantly higher (p 5 0.03 and p <
      0.001 respectively) in strains isolated from patients who had received previous
      treatment. CONCLUSIONS: Monitorization of H. pylori sensitivity to the drugs used
      in its eradication is particularly important in patients who have undergone prior
      treatment.

PMID- 11996702
TI  - [Protein structure: Folding and prions].
AB  - Transmissible spongiform encephalopathies have become a subject of prime social
      concern in recent years because of its relation to "mad cow disease" and their
      potential for transmission to humans. Among the most important scientific aspects
      of these diseases are the peculiar characteristics of the agent involved in their
      transmission. In this article we briefly describe the outstanding features of
      prions, the most widely accepted hypothesis for these diseases. We focus on the
      molecular characteristics of this protein, coded in the genome of the affected
      host, and describe the conformational alterations in the protein's tertiary
      structure that have been blamed for its pathologic activity. Our aim is to
      summarize the state-of-the-art knowledge on prions, the hypotheses proposed to
      explain mechanisms of disease transmission without agents containing genetic
      material, and some specific peculiarities of this new infectious agent. The links
      between this knowledge and possible therapeutic strategies to overcome the
      disease justify, once again, close interaction among chemistry, molecular
      biology, and medicine.

PMID- 11996703
TI  - [Frontal headache and subacute fever in a previously healthy woman].

PMID- 11996704
TI  - [Bite on the scalp and buzzing in the head].

PMID- 11996705
TI  - [Necrotizing fascitis due to Streptococcus pyogenes in two previously healthy
      patients].

PMID- 11996706
TI  - [Interpretive reading of the antibiogram: Intellectual exercise or clinical
      need?].
AB  - Clinical categorisation of susceptibility testing results according to criteria
      established by different committees is daily performed in clinical microbiology
      laboratories. By this process clinicians can predict the therapeutic success of
      antimicrobial treatment in patients infected with susceptible microorganisms. In
      addition, microbiology laboratories that include a suitable number of
      antimicrobial agents in susceptibility tests can perform interpretive reading of
      the antibiogram. With this approach, resistance phenotypes are recognized and
      allow microbiologist: a) detection of mechanisms of resistance, including low
      levels of expression; b) modification of clinical classifications that are
      inconsistent with the inferred resistance mechanism; and c) inference of
      susceptibility values for antimicrobials that are not included in the
      antibiogram. In the laboratory, this approach facilitates quality control and
      validation of susceptibility results. Moreover, it increases the value of the
      results obtained because new mechanisms of resistance can be characterized and
      the epidemiology of resistance can be established. From the clinical point of
      view, this approach contributes to improving the adequacy of treatment (since it
      is useful for predicting therapeutic failure with the use of antimicrobials in
      patients with infections due to resistant microorganisms) and to controlling and
      defining antimicrobial policies. Despite the growing complexity of resistance
      mechanisms, which makes interpretative reading of the antibiogram difficult, this
      process should be incorporated into routine practice in microbiology
      laboratories. Interpretive reading of antibiograms is clinically necessary and
      not simply a intellectual exercise.

PMID- 11996707
TI  - [Low levels of drug resistance in Mycobacterium tuberculosis strains isolated in
      Guipuzkoa (1993-2001)].

PMID- 11996708
TI  - [Infection of shoulder joint prosthesis by Mycobacterium tuberculosis].

PMID- 11996709
TI  - [Nosocomial infection due to Stenotrophomona maltophilia in surgically treated
      patients].

PMID- 11996710
TI  - [The pharmaceutical industry and the funding of scientific societies].

PMID- 11996711
TI  - [Prevalence and detection of depressive disorders in primary care].
AB  - AIM: To study the prevalence of depression in primary care, the detection of
      depressive disorders by primary care physicians, and the factors that influence
      detection. DESIGN: Cross-sectional, descriptive study. SETTING: Gava II Primary
      Care Center, in Barcelona, Spain. PARTICIPANTS: A total of 400 people between the
      ages of 18 and 65 years were chosen randomly from among those who attended
      appointments with their primary care physician. MAIN MEASURES: A sociodemographic
      questionnaire and the Beck Depression Inventory (BDI) screening test were
      administered, and the participant s medical record was reviewed. In a subsample
      of 40 participants, the Mini-International Neuropsychiatric Interview (MINI) was
      also administered. The optimum cutoff score for the BDI was estimated with
      reference to the MINI results. RESULTS: A cutoff score of 20/21 for the BDI had a
      sensitivity of 86.7% and a specificity of 92%, when the MINI score was used as a
      reference. The adjusted prevalence of depressive disorder in our primary care
      setting was 20.2% overall, 8.1% in men, and 26.8% in women (odds ratio 4.15, p <
      0.01). The physician detected depressive symptoms in 55.7% of all likely cases of
      depression. Persons who scored >= 21 on the BDI made more visits to their primary
      care physician, and had more stressful life events, than those who scored 20.
      CONCLUSIONS: The prevalence of depression in our primary care setting is high.
      The disorder was underdiagnosed in as many as 44.3% of the persons likely to have
      depressive disorder (especially women, widows and widowers, retired persons,
      persons who had experienced stressful life events, and frequent users of primary
      care services).

PMID- 11996713
TI  - [Oral anti-coagulants in an urban health centre. The first years results].
AB  - OBJECTIVES: To assess the management of oral anti-coagulation treatment (OAT) by
      family doctors and nurses from a health centre (HC) during its first year.
      DESIGN: Descriptive cross-sectional study.Setting. La Chana, an urban HC in
      Granada, covering 19,362 inhabitants in family care units. PARTICIPANTS: 220
      patients with acenocumarol prescribed during the year 2000. The criterion for
      inclusion was to have at least 3 OAT check-ups a year. 24 people were
      excluded.Interventions. Recruitment by personal invitation at the clinic.
      Capillary blood analyses and dose adjustments by the 10 nurses and 10 family
      doctors of the HC. Internationally recognised therapeutic ranges. MAIN
      MEASUREMENTS: Prevalence of OAT: prescriptions of acenocumarol. Recruitment:
      patients monitored at the HC. INDICATIONS: those found in the clinical records.
      Monitoring: % of patients with INR within range in final annual check-up.
      COMPLICATIONS: rate of haemorrhages, thrombo-embolic accidents and other
      secondary effects. RESULTS: 196 patients followed OAT, a prevalence of 10.12 per
      thousand, with 19.6 patients per family doctor. The HC monitored 122 (62.24%);
      and the hospital, 74 (37.76%). The HC carried out 1,224 check-ups, 208 in the
      homes of 21 patients. There were 70.5% within the therapeutic range. Only 13%
      were in a situation of dose adjustment. Most common indications: non-rheumatic
      auricular fibrillation 65, TVP/TEP 27, mechanical cardiac prostheses 22. There
      were no fatal haemorrhages. Major haemorrhages ran at 2.22% of patients a year;
      and minor ones, at 6.68%. There were no thrombo-embolic accidents. There were two
      skin allergies. CONCLUSIONS: The study showed good results, in line with the
      findings of other studies.

PMID- 11996714
TI  - [Cardiovascular events linked to the new diagnostic categories of diabetes
      mellitus].
AB  - OBJECTIVE: To study the cardiovascular events linked to the new diagnostic
      categories of diabetes mellitus proposed by the American Diabetes Association.
      DESIGN: Descriptive cross-sectional study.Setting. Urban health
      district.Participants. 2248 patients > 14, selected by simple random sampling
      from the medical records archive. MAIN MEASUREMENTS: Through the medical records
      review, patients were classified into those with normal glucaemia, those
      intolerant to glucose when fasting (IGF) and those with type-2 diabetes mellitus
      (DM2). Patients were studied for cardiovascular events, ischaemic cardiopathy,
      cerebrovascular disease and peripheral arteriopathy. The likelihood of such
      events in patients with IGF and DM2 was compared with normal-glucose patients
      through logistical regression, adjustment for age, gender, hypertension,
      hypercholesterolaemia, hypertriglyceridaemia and tobacco dependency. RESULTS:
      1677 patients were classified: 1237 with normal glucaemia, 175 with IGF and 265
      with DM2. The DM2 patients were more likely to have at least one cardiovascular
      event (OR, 2.7; 95% CI, 1.7-4.4), ischaemic cardiopathy (OR, 2.0; 95% CI, 1.1
      3.6), cerebrovascular disease (OR, 3.0; 95% CI, 1.4-6.6) or peripheral
      arteriopathy (OR, 2.9; 95% CI, 1.2-7.7). Results reached no statistical
      significance in patients with IGF, though these were more likely to suffer a
      cardiovascular event (OR, 1.1; 95% CI, 0.6-2.1), ischaemic cardiopathy (OR, 1.1;
      95% CI, 0.3-4.4), cerebrovascular disease (OR, 1.5; 95% CI, 0.5-4.1) or
      peripheral arteriopathy (OR, 1.2; 95% CI, 0.3-4.6). CONCLUSIONS: Patients with
      DM2 are more likely to present cardiovascular events, a phenomenon not seen in
      the case of IGF.

PMID- 11996715
TI  - [Principal requirements in medical training for certification of deaths in
      Spain].
AB  - OBJECTIVE: To know the training need priorities in Spanish physicians in death
      certification. DESIGN: Study of needs by consensus technique Delphi. SETTING:
      Health care and medical-legal institutions in Spain. PARTICIPANTS: Physicians who
      ask for information in death certification, after reading an article in a medical
      magazine (n=38), and agree to participate (n=33). METHODS: Priorities were
      established by means of a list of items, based on teaching experience and
      professional advice. The scores obtained for each priority were hierarchized, and
      the participants professional profiles were described. An analysis of
      hierarchical clusters was done to determine profiles of training. RESULTS: The
      median age of the participants was 42 years, with 18 years experience in
      general/family, emergency or forensic medicine, which usually certified in median
      8 death a year (rank from 0 to 50). The maximum training priorities were how to
      register a death and which doctor should make out the official documents.
      Intermediate priorities included the role of doctors in violent or accidental
      deaths. In the main three grouping needs were, in one, include certification as a
      degree subject and learn how different documents are made out; although in the
      others two, were how to register a death, which physician make out the documents,
      and when it should certify the family doctor and when the coroner. CONCLUSIONS:
      The priorities in certification training are how to register a death and who
      should make out the documents, pointing out that the shortcoming continues in
      medical training in death certification.

PMID- 11996716
TI  - [Reflections on antileukotrienes].

PMID- 11996717
TI  - [2002 contraception panorama].

PMID- 11996718
TI  - [Step by step in the design of a focus group-based study].

PMID- 11996719
TI  - [Diagnosis and treatment of chronic cancer pain (I)].

PMID- 11996720
TI  - [Evaluation in the clinic of health-related quality of life: the COOP/WONCA
      cartoons].

PMID- 11996721
TI  - [Back pain in nursing staff and its prevention].

PMID- 11996722
TI  - [Ingrown nails: one-year experience with nail surgery in the primary care
      clinic].

PMID- 11996723
TI  - [semFYC Congress: a scientific investment or a source of income?].

PMID- 11996724
TI  - [Congratulations letter].

PMID- 11996725
TI  - [Reply of family medicine to the Declaration of Granada].

PMID- 11996726
TI  - [Influence of type of infant feeding and other factors on the incidence of
      respiratory tract infections in infants followed at a primary care center].
AB  - OBJECTIVE: To determine the influence of type of infant feeding on the incidence
      of lower (LRTI) and upper respiratory tract infections during the first 12 months
      of life. DESIGN: Historical cohort study. SETTING: Primary care centers.
      PARTICIPANTS: A total of 250 babies born at term between October 1, 1994 and
      February 1, 1998. INCLUSION CRITERIA: current medical record available at a
      participating primary care center, participation in a Healthy Baby Program,
      residence in the basic health area involved in the study, birth weight #>2500 g.
      Interventions. Breastfeeding alone or in combination with formula feeding;
      artificial feeding alone. MAIN OUTCOME MEASURES AND RESULTS: Attending day care,
      antecedents of atopy, fathers and mothers smoking habit, parents level of
      education, number of persons in the household, mothers age. There was no
      association between type of feeding and the incidence of respiratory infections.
      All 95% confidence intervals (95% CI) of the odds ratios (OR) included the value
      of 1. At age 3 months, LRTI was associated with the number of persons in the
      household (OR, 1,87; 95% CI, 1.18-2.95) and with antecedents of atopy (OR, 2.96;
      95% CI, 1.19-7.4). At age 6 months, LRTI was associated with the number of
      persons in the household (OR, 1.62; 95% CI, 1.07-2.44) and with attending day
      care (OR, 4.52; 95% CI, 1.20-17.1). CONCLUSIONS: In the present study
      breastfeeding was not effective in lowering the incidence of respiratory
      infections.

PMID- 11996727
TI  - [Breastfeeding and respiratory infections].

PMID- 11996728
TI  - [Levels of serum cholesterol in a catalan population. Evolution over a 6- year
      period (1994-1996)].
AB  - OBJECTIVE: To study the evolution of the serum levels of cholesterol in a
      population over 6 years. Design. cross-sectional observational study.Setting.
      Primary and specialist care in the county of Osona (Barcelona). PARTICIPANTS:
      Study of those patients attending for health consultations in the county, whether
      at primary or hospital level, and who had their cholesterol level determined.
      MAIN MEASUREMENTS: The levels of serum cholesterol of the 7882 patients studied
      during September to December 1994 was compared with those of the 10 319 patients
      analysed during the same months of 1999. RESULTS: The mean levels of cholesterol
      increased steadily in both sexes with age, up to the fifth or sixth decade of
      life, at which point a slow descent started. Cholesterolaemia was higher in men
      than in women in the third and fourth decades of life; but from this age on, mean
      levels are higher in women than in men. Cholesterol levels in both sexes were
      higher in the 1999 period studied than in 1994. During 1999, 52.7% of men and
      52.3% of women had serum cholesterol levels above 200 mg/dL, whereas in 1994
      these figures were 49.1% and 49.2%, respectively. CONCLUSIONS: Mean levels of
      serum cholesterol in the population under study are high and increased between
      the two sampling years. Preventive and hygiene-diet measures need to be fomented
      among the general population in order to improve control of cholesterolaemia.

PMID- 11996729
TI  - [The integrated management software of primary care,a tool for analysing
      indicators of use].
AB  - OBJECTIVES: To analyse the indicators of use in the Gran Canaria Health Area. To
      characterise over-users so that the primary care team can take corrective
      measures. To design a computer tool giving appropriate useful information to the
      management, that can be directly put into practice in primary care. DESIGN:
      Retrospective descriptive study. SATTING: Gran Canaria Health Area. Hierarchical
      descent in the analysis of data in the base health area and family care unit, in
      the year 2000. PARTICIPANTS: Users of the Canaries Health Service registered on
      the individual health card data base. MAIN MEASUREMENTS AND RESULTS: The activity
      generated by 636 270 users with 2 876 394 appointments was studied. Mean
      frequency of attendance in the Gran Canaria Health Area was 4.52, with a 67.3%
      use rate. The user causing 11 or more visits per year was defined as an over
      user. 13.4% of users were over-users and caused among them 52.3% of visits. 32.7%
      of users registered made no visit. CONCLUSIONS: A small section of the population
      causes over half the consultations. The characteristics of these users need to be
      analysed so that programmes can be worked out to decrease their frequency of use.
      The integrated management software for primary care enables this information to
      be analysed and serves as a support for the primary care teams. Special attention
      needs to be paid to the population that does not use the health centres.

PMID- 11996730
TI  - [Burnout in primary care doctors of the province of caceres].
AB  - OBJECTIVES: To analyse the degree of professional burnout in primary care doctors
      from our province and the effect of various factors.Design. Descriptive and
      analytic cross-sectional study. SETTING: Primary care (PC) in the province.
      PARTICIPANTS: All the PC doctors in the province of Caceres (n=255). MAIN
      MEASUREMENTS AND RESULTS: Self-administered anonymous questionnaire: the Maslach
      Burnout Inventory that evaluates Depersonalisation (DP), Self-esteem (SE), and
      Emotional Exhaustion (EE); social and personal variables, work data, personal
      questions and measures taken if there was work stress. Student s t test, ANOVA
      (means), and Chi-square or Fisher test (percentages) were used. 157 valid
      questionnaires were returned (62% response rate). Mean age was 41.5 years old
      7.2; 75% were male, 80.2% married, 73.2% had tenure, 48.9% worked in towns, and
      their mean case-load was 40.5 16.5 patients/day. Mean values found were: DP, 8.3
      5.8; SE, 35.2 8.4; EE, 22 11.3; 65.8% scored high on one of the three. For EE
      mean scores were significantly higher in men, doctors with tenure, in towns,
      those with >10 years seniority or who saw >40 patients a day. 50% had had psycho
      physical disorders in the previous 3 months; 33% withstood a lot of bureaucracy;
      both groups had <SE and >EE averages. Dedicating <2 hours a day to leisure was
      associated with >EE; and being a tutor with a significantly higher level of
      burnout. Disorders in the family or social/work sphere were associated with high
      levels of DP and EE (P<.001). CONCLUSIONS: Like other studies, we found a
      moderate level of burnout in our sample. Seniority, social/labour or family
      conflict, and certain personal and job characteristics were associated with high
      burnout.

PMID- 11996731
TI  - [New technological solutions to the problem of repeat prescriptions].

PMID- 11996733
TI  - [Immunisation: leaps into the future. Primary Care vaccination: new aspects of an
      old activity].

PMID- 11996734
TI  - [Impact of the commercialisation of transdermic fentanyl on the home care of
      terminal cancer patients].

PMID- 11996735
TI  - [Family support network of patients with chronic renal failure].

PMID- 11996736
TI  - [Paediatricians: from colleague working alongside to friend in consultations].

PMID- 11996738
TI  - [Current suspect and diagnosis of pulmonary thromboembolism].

PMID- 11996739
TI  - [The current clinical spectrum of pulmonary thromboembolism].
AB  - BACKGROUND. Mortality in pulmonary thromboembolism (PTE) decreases considerable
      when it is diagnosed early. The suspicion based on clinical and complementary
      data is essential for an early diagnosis. METHODS. Retrospective review of the
      clinical features in patients diagnosed of PTE in an Internal Medicine department
      from January 1993 to December 1999. RESULTS. A total of 117 patients with PTE
      were identified. The median age was 68.8 years. Sixty-six patients (56.4%) had
      one or more risk factors for PTE. The most common risk factor was immobilization
      (37.6%). Dyspnea was the most common symptom (74.4%) and tachypnea the most
      common sign (66.7%). Fever/low grade fever and leukocytosis were present in 16.2%
      and 31.6% of patients, respectively. Respiratory failure, alkalosis and
      hypocapnia were present in 44.4%, 38.5% and 47% of patients, respectively. An
      alveolar-arterial oxygen gradient > 20 mmHg was demonstrated in 96.6% of
      patients. Chest radiographs and electrocardiograms were normal in 52.1% and 23.9%
      of patients, respectively. A vein echo-duplex of the lower limbs demonstrated
      deep vein thrombosis (DVT) in 52.1% of patients. The hospital mortality rate was
      6.8%. CONCLUSIONS. PTE still affects older patients mainly and frequently known
      risk factors are not detected. The presence of fever/low grade fever and/or
      leukocytosis does not rule out PTE. Both chest radiographs and electrocardiograms
      may be normal. Not demonstrating DVT in the lower limbs by the vein echo-duplex
      does not rule out PTE. The hospital mortality rate has not decreased considerably
      in the last few years.

PMID- 11996740
TI  - [Incidence of gestational diabetes mellitus according to different diagnostic
      criteria in the southeast Madrid area. Influence of diagnosis on materno-fetal
      parameters].
AB  - BACKGROUND. In 1997, The Fourth International Workshop-Conference on Gestational
      Diabetes Mellitus (GDM) recommended the use of Carpenter and Coustan diagnostic
      criteria instead of those of Sullivan and Mahan used until then. The objective of
      this work was to study the incidence of GDM in the southeast Madrid area by
      applying both the classical and new criteria, as well as to determine whether
      patients diagnosed of GDM by the new criteria present a higher materno-fetal
      morbidity than treated GDM patients or non diabetic pregnant patients.Methods.
      Review of a cohort of 1,293 pregnant women from September 1998 to August 1999 who
      were screened for GDM. The annual cumulated incidence of GDM was estudied by
      using both diagnostic criteria and materno-fetal evolution of four groups of
      patients classified according to glucose intolerance degree. RESULTS. The annual
      cumulated incidence of GDM was 4.8% and 7.3% using the classical criteria and the
      new criteria, respectively. GDM patients fulfilling only the new criteria and not
      treated as such had children with a significantly higher birth-weight than the
      other groups, and a trend towards a higher percentage of macrosomies,
      instrumental deliveries and cesarean sections in such group was observed,
      although they were not statistically significant. CONCLUSIONS. The incidence of
      GDM in the southeast Madrid area was similar to that among other Caucasian
      populations and increased by 52% when the new diagnostic criteria were used. It
      is our opinion that a study with a larger number of patients should be conducted
      before the new diagnostic criteria are applied in our country.

PMID- 11996741
TI  - [Ambulatory parenteral antimicrobial therapies. Five-year experience].
AB  - INTRODUCTION. To report the five-year experience in ambulatory parenteral
      antimicrobial treatments of a Hospital at Home (HH). METHODS. Prospective,
      descriptive study in which demographic data, infection types, antibiotics,
      dosages, treatment duration, administration methods, and complications were
      recorded. RESULTS. A total of 325 ambulatory parenteral antibiotic treatments
      were instituted. The mean age of patients was 56 years (range: 4-96). Patients
      included 225 men and 100 women. The mean duration of treatment was 16 days
      (range: 1-176 days). The total number of stays was 4,313 days. The sources of the
      treated infections included: respiratory tract, 40.3%; osteoarticular, 13.2%;
      digestive tract, 7%; cytomegalovirus, 6.4%; soft tissue, 5.5%; bacteremias, 5,2%;
      central nervous system, 4.9%; urinary tract, 4.6%; febrile syndromes, 3.7%;
      postsurgical, 3%; and endocarditis, 2.5%. Ceftriaxone was the antibiotic most
      widely used. Seventy-nine percent of treatments were throught the intravenous
      route. In the last two years infusion pumps were used. Treatment was completed in
      93.3% of cases, three patients died and 19 patients required readmission. The
      most common complication was phlebitis, in 12.6% of cases. CONCLUSIONS.
      Currently, there is the possibility of safely treating a large number of
      infections at patient's home with parenteral antibiotics.

PMID- 11996742
TI  - [Toxoplasmosis after antineoplastic therapy in non-Hodgkin lymphoma. Demand of
      preventive measures].
AB  - BACKGROUND. Toxoplasmosis is an opportunistic infection reported in several
      groups of inmunosupressed patients. It is considered uncommon in patients with
      lymphoproliferative disorders and in bone marrow transplant recipiets (BMT).
      Nevertheless, recent reviews have reported cases of cerebral and disseminated
      toxoplasmosis in BMT recipients, particularly among patients with IgG antibodies
      to Toxoplasma sp. prior to BMT and antineoplastic treatment. PATIENTS AND
      METHODS. Two cases of toxoplasmosis are reported of patients with non-Hodgkin
      lymphoma who did not have graft-versus-host-disease and with positive
      antitoxoplasma serologic response. In the first patient, the predominant clinical
      picture was febrile neutropenia without source, with good response to specific
      treatment for toxoplasmosis; in the second patient, and autologous BMT was
      performed and six months later the patient developed a retino-choroiditis by
      toxoplasmosis reactivation. CONCLUSIONS. The excessive morbidity and mortality
      associated with toxoplasmosis reactivations in lymphomyeloproliferative neoplasms
      with antineoplastic therapy and both allogenic and autologous BMT, demand
      preventive measures. The pretransplant serologic tests can be helpful in
      evaluating the potential risk of suffering a reactivation by Toxoplasma sp. and
      considering the administration of chemoprophylaxis in selected patients with
      positive serology.

PMID- 11996743
TI  - [Diagnostic attitudes in non-cardiogenic pulmonary edema].

PMID- 11996744
TI  - [Indications of new surgical techniques of myocardial revascularization].

PMID- 11996745
TI  - [Indications for the intravenous use of immunoglobulins].

PMID- 11996746
TI  - [Treatment of non-complicated essential arterial hypertension].

PMID- 11996747
TI  - [Abdominal pain and jaundice].

PMID- 11996748
TI  - [Hypertensive crisis in a 28-year old woman].

PMID- 11996749
TI  - [Fifty-two year old woman with repeated vomiting].

PMID- 11996750
TI  - [Fever and vesicular lesions over photo-exposed areas].

PMID- 11996752
TI  - [Scabies outbreak among drug abusers].

PMID- 11996751
TI  - [A new case of hantavirus disease in Spain?].

PMID- 11996753
TI  - [Infection caused by human herpesvirus-6 and organ transplantation].

PMID- 11996754
TI  - [Infection due to parvovirus B19 with a petechial rash in an adult patient].

PMID- 11996755
TI  - [Pure red cell aplasia and myelodysplastic changes].

PMID- 11996756
TI  - [Internal Medicine an prevalent diseases. Heart failure case].

PMID- 11996757
TI  - [Cost savings derived from the participation in clinical trials].
AB  - BACKGROUND: Medical care of patients with essential hypertension implies
      considerable expenses for the National Health System (NHS). During the
      performance of clinical trials (CT), the promoter (usually the pharmaceutical
      industry) covers the expenses of patient care, which implies savings for the NHS.
      In this work, we quantitated cost savings derived from the participation of
      patients in clinical trials on essential hypertension in a tertiary care level
      Insalud hospital. PATIENTS AND METHODS: Savings were defined as the difference
      between the economical expenses of a patient before being enrolled in a clinical
      trial (CT) and that generated during his/her participation in the CT. Expenses of
      a given patient to the NHS were calculated from his/her clinical record during a
      time period equal to CT length in which the patient participated. Three financial
      allottments in four CT were analyzed (three with a 52-week duration and one of 14
      weeks) that meant cost savings (total or partial): a) antihypertensive drugs; b)
      complementary tests, and c) medical visits. RESULTS: Seventy-three patients with
      essential hypertension were enrolled in the 4 CT; 59 (81%) patients were randomly
      assigned and 57 patients concluded the CT. The overall savings derived from the
      participation of the 57 patients was 2,950,423 pesetas. Most of these savings
      corresponded to drugs (70.7%). Savings derived from laboratory tests (14.1%) and
      medical visits (15.1%) were similar. The mean savings derived from the
      participation of one patient in a CT for 12 months was, at least, 70,564 pesetas
      (5,880 pesetas/patient/month). CONCLUSIONS: The participation of patients with
      essential AH implies considerable savings for the NHS.

PMID- 11996758
TI  - [The carpal tunnel syndrome in the oil toxic syndrome].
AB  - BACKGROUND: The toxic oil syndrome (TOS) is an autoimmune disease caused by the
      ingestion of aniline-denatured rapeseed oil. The carpal tunnel syndrome (CTS) is
      an entrapment neuropathy due to the median nerve entrapment, which is associated
      with both occupational activities and autoimmune diseases. The objective of this
      work was to know the frequency and characteristics of CTS in TOS patients.
      PATIENTS AND METHODS: Between December 1977 and July 2000, 744 TOS patients were
      evaluated. The inclusion criteria were: the clinical records for patients
      diagnosed between May 1981 and November 1997; and for patients diagnosed between
      December 1997 and July 2000, symptoms with the classical or likely pattern
      according to the Katz's hand diagram and one of the following findings: a)
      abnormal electromyogram, and b) hypalgesia in the median nerve territory and
      positive Tinel and/or Phalen signs. RESULTS: A total of 70 patients (63 women,
      90%) were diagnosed; 48 of them had been diagnosed before 1997 and 22
      subsequently. The mean age of patients was 47.6 (20-78) years. In 36 patients
      (51.4%), a bilateral CTS was present. Fifty-six patients (81.4%) had a diagnostic
      EMG, and 31 (44.2%) were obese, 13 (18.6%) diabetic, and 4 (6%) had
      hypothyroidism. Most of these cases (48; 68.6%) were housewives. CONCLUSIONS: TOS
      patients have a high frequency of CTS; therefore, this condition must be
      suspected in patients with associated obesity and diabetes mellitus.

PMID- 11996759
TI  - [Evaluation of an advisory program in antibiotic therapy].
AB  - BACKGROUND: Increases in microbial resistance and pharmaceutical costs have
      prompted an interest in antibiotic control programs (ACP). Nevertheless, there is
      controversy on the optimal ACP design and implementation. An ACP based on the
      infectious diseases' specialist recommendations was evaluated. METHODS:
      Interventional study of two hospital departments (medical and surgical).
      Antibiotic costs, mortality rate, readmissions following an infectious disease,
      and incidence of MRSA and Clostridium difficile between the intervention period
      and the same period in the previous year were compared. An anonymous survey among
      health care workers in both departments was conducted. RESULTS: One-hundred and
      one antimicrobial therapy courses administered to 80 patients were evaluated. A
      total of 77 recommendations were issued, which consisted of therapy
      discontinuation (39%), switch to oral antibiotics (31%), decrease in the
      antimicrobial spectrum (24%) or enhancing the antimicrobial spectrum (6%). Eighty
      five percent of the recommendations were accepted. The antimicrobial use remained
      stabilized, but the oral administration increased from 12.5 to 18.6 DDD/100
      patient-days and parenteral use decreased from 25.9 to 22.3 DDD/100 patient-days.
      Antimicrobial costs decreased by 19.4% (901,794 pesetas). No changes, either in
      the mortality rate or in readmission rate due to infectious diseases was
      observed. In contrast, a decrease in the incidence of both MRSA (3.7% to 0.8%; p
      < 0.05) and Clostridium difficile (1.2% to 0%; p = 0.05) was observed. All health
      care workers that responded to the survey thought that ACP should be extended to
      the rest of the hospital. CONCLUSIONS: Our ACP, based on the advice of an
      infectious diseases specialist, was very well accepted and allows for a decrease
      in antibiotic costs by simplified therapy. The ACP did not cause a negative
      impact on patients' outcomes and would probably help reducing the incidence of
      some nosocomial pathogens.

PMID- 11996760
TI  - [Spontaneous pneumothorax and atmospheric pressure].
AB  - In order to assess factors associated with spontaneous pneumothorax (SP), mainly
      climatic changes, a prospective study was undertaken of 62 SP episodes among
      patients admitted to our hospital during a two-year period, from January 1994 to
      January 1996. Atmospheric pressure (AP) changes were analyzed, with daily
      recording of the number of unusual changes in AP (increases above 95th percentile
      and decreases below 5th percentile) and how many of these changes were followed
      by some episode of spontaneous pneumothorax during the following five days. To
      measure the degree of this association between the emergence of pneumothorax and
      exposure to unusual changes I AP, the relative risk (RR) was calculated. A total
      of 77 unusual AP changes were observed, 17 of which concurred with the emergence
      of 8 episodes of SP during the following five days, with a RR of 2.7 (1.6-4.4).
      Although the etiology of SP is unknown and probably of multifactorial origin,
      these data suggest that unusual changes in AP may play a relevant role in
      triggering this condition.

PMID- 11996761
TI  - [Diagnosis of depressive equivalents].

PMID- 11996762
TI  - [Diagnosis of myopathies].

PMID- 11996763
TI  - [Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis)].

PMID- 11996764
TI  - [Indications for surgical myocardial revascularization in ischemic myocardial
      disease].

PMID- 11996765
TI  - [Helicobacter pylori infection].

PMID- 11996766
TI  - [Transient intestinal invagination in a 15-year old male].

PMID- 11996767
TI  - [Liver disease and cutaneous lesions].

PMID- 11996768
TI  - [Pneumoperitoneum in an 81-year old woman].

PMID- 11996769
TI  - [Patient with constitutional syndrome and multiple masses].

PMID- 11996770
TI  - [Peripheral eosinophilia and cutenous lesions].

PMID- 11996771
TI  - [Infective endocarditis due to Actinobacillus actinomycetemcomitans on native and
      prosthetic valve].

PMID- 11996772
TI  - [Acute pleuropericarditis in a patient with Crohn's disease controlled with
      chronic therapy with mesalazine].

PMID- 11996773
TI  - [Spontaneous spleen rupture and Q fever].

PMID- 11996774
TI  - [Systemic inflammatory response syndrome and disseminated intravascular
      coagulation: Sweet syndrome].

PMID- 11996775
TI  - [Listeria monocytogenes and ulcerative colitis].

PMID- 11996777
TI  - Adolescent health and terrorism--the role of the adolescent medicine specialist.

PMID- 11996778
TI  - Supporting adolescents in times of national crisis: potential roles for
      adolescent health care providers.

PMID- 11996779
TI  - The effects of terrorism on teens' perceptions of dying: the new world is riskier
      than ever.
AB  - Adolescents assessed after the September 11, 2001 terrorist attacks perceived the
      risk of dying from general causes, a tornado, and an earthquake as dramatically
      higher than did adolescents assessed years before the attacks. Adolescents'
      heightened perceptions of vulnerability to death extended beyond the terrorist
      acts, and generalized to unrelated risks.

PMID- 11996780
TI  - Emergency management of the adolescent suicide attempter: a review of the
      literature.

PMID- 11996781
TI  - Coping styles as correlates of health in high school students.
AB  - PURPOSE: To study a large, population-based sample of adolescents with the goal
      of expanding our knowledge base about the relationship of coping and health
      outcomes. METHOD: We examined 1769 nonclinical, high school students (48% girls,
      mean age 16 years, predominantly white) using one class period to establish a
      link between coping styles, health problems, and health risk behaviors.
      Instruments employed included the Coping Response Inventory - Youth form
      (abbreviated version) and the Juvenile Wellness and Health Survey. ANCOVAs were
      used to test the main effects of coping typology, gender, and their interaction
      on the five health domains. RESULTS: Findings were consistent with previous
      research and showed that approach coping correlated negatively with indicators of
      health problems and health risk behaviors, while avoidance coping correlated
      positively with these domains. The presence of both forms of coping mitigated the
      negative effects of avoidance coping. CONCLUSION: As early as mid-adolescence,
      habitual coping styles appear to be associated with significant health outcomes.
      In screening nonclinical samples the clinician can rely on habitual coping styles
      as indicators of potential health problems.

PMID- 11996782
TI  - Adolescent victimization and subsequent use of mental health counseling services.
AB  - PURPOSE: To test the extent to which adolescent victimization predicts subsequent
      use of mental health services in a prospectively assessed nationwide sample of
      high school students. METHODS: Data were analyzed from 4590 adolescents
      participating in Waves I and II of the National Longitudinal Survey of Adolescent
      Health. In-home self-report data were collected on four types of personal
      victimization, mental health service use, demographics, psychological
      symptoms/needs, and family connectedness. Using logistic regression analysis,
      adolescents' victimization and background variables at Wave I were entered as
      predictors of subsequent mental health service use, measured at Wave II. RESULTS:
      In this national sample, 19.6% of the respondents stated that they had
      experienced at least one of four forms of personal victimization in the prior
      year. Of those reporting personal victimization, 11.0% stated they had used
      mental health services at 1-year follow-up, as compared to 9.2% of those who did
      not report any personal victimization. After controlling for background variables
      in logistic regression analyses, however, adolescents' victimization reported at
      Wave I was associated with significantly lower odds of subsequent mental health
      service use at Wave II. CONCLUSIONS: Evidence does not indicate that adolescents'
      victimization prompts mental health service use, and rather indicates that in
      some instances victimization is associated with lower odds of subsequent mental
      health service use. These findings raise questions about the degree to which
      adolescents receive needed professional mental health supports in the wake of
      serious violence exposure.

PMID- 11996783
TI  - Planning youth violence prevention efforts: decision-making across community
      sectors.
AB  - PURPOSE: To identify practical components of decision-making for youth violence
      prevention program planning and to identify differences in decision-making across
      various provider sectors of the community. METHODS: Data were collected in seven
      focus groups (n = 82) representing seven key sectors of the community involved in
      youth violence prevention activities (e.g., educators, law enforcement officers,
      and healthcare providers). Discussion was guided by a series of open-ended
      questions that we developed. Transcript-based content analysis using NVivo
      software identified common themes among and across sectors. RESULTS: Similarities
      and differences in planning and selecting prevention efforts were found across
      sectors. Educators targeted behaviors that disrupt the school process, while
      other sectors focused on precursors and concurrent factors of violent behavior
      and the development of desirable behaviors. Public health and public policy
      participants underscored outcome measures, benchmarks, and a match between
      funding and effective programs as essential elements. Youth identified the need
      for respect from adults and the recognition of positive youth behaviors. All
      groups noted the lack of a systematic method of considering potential programs,
      the importance of youth and parental involvement in efforts, the lack of a
      scientific base for many programs, concerns about exposure to violence, and
      inappropriate role models in multiple environments. CONCLUSIONS: Healthcare
      providers often participate in the development of youth violence prevention
      programs. Understanding similarities and differences in focus among key sectors
      of the community is essential in developing coordinated interdisciplinary
      approaches.

PMID- 11996784
TI  - Partner violence among homeless young adults: measurement issues and
      associations.
AB  - PURPOSE: The primary goal of this study was to test the reliability of the
      Partner Violence Interview and examine validity by measuring differential
      correlates of partner violence. METHODS: Sixty young adults (30 males and 30
      females) housed in an urban shelter participated in this study. All participants
      were between the ages of 18 and 21 years and the majority were African-American.
      The participants were administered two measures of partner violence exposure, one
      measure of community violence exposure and one measure of depression. A random
      selection of 30 of the participants was retested after 1 month. RESULTS: As
      predicted, current and past partner violence was common in this sample, with over
      70% endorsing a history of physical violence. The Partner Violence Interview
      (PVI) had adequate retest reliability (Pearson r for two PVI scales =.7 and.85)
      and internal consistency (KR-20 for each scale =.78 to.93). Preliminary evidence
      of convergent validity was suggested by the fact that the PVI lifetime partner
      violence scale was significantly correlated with a physical violence scale from a
      second measure (the Conflict Tactics Scale; r =.596, p <.001). Violence in past
      relationships, as opposed to current relationships, was associated with both
      lifetime community violence exposure and current level of depression.
      CONCLUSIONS: The Partner Violence Interview is a reliable, comprehensive
      instrument suited to high-risk populations. Homeless young adults commonly
      experience severe partner violence, and preventive intervention is clearly
      indicated for this group.

PMID- 11996785
TI  - Effects of at-school victimization and sexual orientation on lesbian, gay, or
      bisexual youths' health risk behavior.
AB  - PURPOSE: To examine the link between victimization at school and health risk
      behaviors using representative data comparing lesbian, gay, and bisexual (LGB)
      youths and heterosexual youths. METHODS: Data from the 1995 Youth Risk Behavior
      Survey taken in Massachusetts and Vermont were examined. This sample included
      9188 9th through 12th grade students; 315 of these students were identified as
      LGB. Analyses of variance were used to examine health risk behaviors by sexual
      orientation by gender by victimization level. RESULTS: The combined effect of LGB
      status and high levels of at-school victimization was associated with the highest
      levels of health risk behaviors. LGB youths reporting high levels of at-school
      victimization reported higher levels of substance use, suicidality, and sexual
      risk behaviors than heterosexual peers reporting high levels of at-school
      victimization. Also, LGB youths reporting low levels of at-school victimization
      reported levels of substance use, suicidality, and sexual-risk behaviors that
      were similar to heterosexual peers who reported low at-school victimization.
      CONCLUSIONS: The findings provide evidence that differences in health risks among
      LGB youth are mediated by victimization at school. Such victimization of LGB
      youth is associated with health risk behaviors.

PMID- 11996786
TI  - History of family dysfunction and perpetration of dating violence by adolescent
      boys: a longitudinal study.
AB  - PURPOSE: To examine whether there is a direct or a mediated association between
      dysfunctional parental behavior in later childhood and involvement in dating
      violence in a sample of low socioeconomic-status boys during mid-adolescence.
      METHODS: Subjects were 717 boys who participated in a longitudinal study. Data
      collected at six time periods, beginning at age 10 years and covering a span of 8
      years, were analyzed. Dysfunctional parental behavior patterns were defined as
      perceived harsh parenting practices, laxness of monitoring, and interparental
      conflict witnessed by the subject. Perpetrated psychological and physical abuse
      in dating, measured at ages 16 and 17 years, and delinquency, measured at age 15
      years, served as dependent measures. All instruments were self-report
      questionnaires. Multiple regression analysis was used in data analysis. RESULTS:
      Only two variables contributed independently to dating violence. Boys who
      perceived laxness of monitoring from their parents in their late childhood and
      reported antisocial behavior at age 15 years, such as delinquency and substance
      abuse, were at risk of becoming involved in violent dating relationships at age
      16 years. Harsh parenting practices from ages 10 to 12 years were also predictors
      of dating violence. CONCLUSIONS: A direct relationship was found between harsh
      parenting and antisocial behavior and later dating violence. No support was found
      for the mediation hypothesis of antisocial behavior, but an indirect influence
      was noted in association with monitoring.

PMID- 11996787
TI  - Analysis of the NF2 gene in oligodendrogliomas and ependymomas.
AB  - Allelic losses of chromosome 22 are commonly found in ependymomas and
      oligodendrogliomas, suggesting that at least one tumor suppressor gene on
      chromosome 22 must be inactivated during the multistep process of tumorigenesis
      in these glial tumors. The neurofibromatosis 2 gene (NF2) located at 22q12, is a
      candidate tumor suppressor gene potentially involved in the pathogenesis of
      gliomas. Because there have been only a few studies of the NF2 gene in glial
      tumors other than astrocytoma, we screened the entire 17 NF2 exons for mutations
      in a series of 47 nonastrocytic tumors, including 40 oligodendrogliomas and 7
      ependymomas. Only one mutation was detected, a 59-base pair insertion in exon 3
      from a spinal anaplastic ependymoma. These results concur with previous findings
      proposing preferential inactivation of the NF2 gene in a subgroup of ependymomas,
      and suggest that the NF2 gene is not the target of chromosome 22 aberrations in
      oligodendrogliomas.

PMID- 11996788
TI  - Cytogenetic and molecular analysis of early stage renal cell carcinomas in a
      family with a translocation (2;3)(q35;q21).
AB  - Previously, we described a family with renal cell carcinoma (RCC) and a
      constitutional balanced t(2;3) (q35;q21). Based on loss of heterozygosity and von
      Hippel-Lindau (VHL) gene mutation analyses in five tumor biopsies from three
      patients in this family, we proposed a multistep model for RCC development in
      which the familial translocation may act as a primary oncogenic event leading to
      (nondisjunctional) loss of the translocation-derived chromosome 3, and somatic
      mutation of the VHL gene as a secondary event related to tumor progression. Here,
      we describe the cytogenetic and molecular analysis of three novel tumors at early
      stages of development in two members of this family. Again, loss of derivative
      chromosome 3 was found in two of these tumors and a VHL mutation in one of them.
      In the third tumor, however, none of these abnormalities could be detected. These
      results underline our previous notion that loss of derivative chromosome 3 and
      VHL gene mutation play critical roles in familial RCC. In addition, they show
      that both anomalies may occur at relatively early stages of tumor development.

PMID- 11996789
TI  - Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and
      adenomas.
AB  - Deletion of chromosome 11q23 is a common alteration in parathyroid adenomas and
      hyperplasias. A new potential suppressor gene PPP2R1B encoding the beta isoform
      of the A subunit of the serine/threorine protein phosphatase 2A was recently
      identified and localized to chromosome 11q23. We performed polymerase chain
      reaction-based single-strand conformation polymorphism and direct sequencing on
      six parathyroid hyperplasias and 12 adenomas to evaluate the role of PPP2R1B in
      the pathogenesis of parathyroid lesions. A previously identified germline G-A
      transition (GGC-GAC) in codon 90, changing glycine (Gly) to aspartic acid (Asp),
      was detected in one adenoma. Both the common Gly allele and the variant Asp
      allele were detected by direct sequencing in the patient's somatic cells. We
      conclude mutations of PPP2R1B are not frequent in parathyroid lesions, and that
      other genes located at 11q23 may be more closely associated with pathogenesis of
      parathyroid hyperplasia and adenoma.

PMID- 11996790
TI  - Fluorescence in situ hybridization improves cytogenetic results in the analysis
      of hepatoblastoma.
AB  - Hepatoblastoma (HB) is the most frequent malignant liver tumor in children.
      Cytogenetic data indicate the presence of recurring trisomies of the chromosomes
      2, 8, and 20, but more work is needed to clarify their incidence and prognostic
      significance. Cytogenetic analysis is limited by the requirement of suitable
      cells in metaphase. A different method that increases analysis sensitivity is
      fluorescence in situ hybridization (FISH). We studied 20 cases of hepatoblastoma;
      FISH analysis obtained results in 10 cases of HB with no informative karyotype.
      In 5 of 10 of these cases at least one trisomic clone was detected, which always
      coexisted with a population of diploid cells. These results confirm that trisomy
      20 and/or 2 and 8 coexisting with diploid cells is a frequent finding in
      hepatoblastoma and provide further support to the clonal evolution theory:
      indeed, trisomy 20 was the most frequently detected abnormality, followed by
      trisomy of chromosomes 2 and 8. In view of the high incidence of recurrent
      trisomies, FISH analysis should be recommended in all the cases of HB with no
      informative karyotype.

PMID- 11996791
TI  - Significance of cytogenetic and fluorescence in situ hybridization analysis in
      evaluating antichronic myeloid leukemia efficacy of different immune effector
      cells.
AB  - We report on the antileukemia effect of interleukin 2 (IL2) on different immune
      cells from 22 patients with chronic myeloid leukemia (CML). Bone marrow cells
      from these patients were first cultured in modified long-term bone marrow culture
      medium for several days, then separately cultured with lymphokine activated
      killer cells (LAK), cytokine-induced killer cells (CIK), and dendritic cell
      cocultured CIK (DC-CIK) for another 1-2 days. They were then detected for
      presence of the Philadelphia chromosome (Ph) by cytogenetic analysis and
      fluorescence in situ hybridization (FISH). The percentage of Ph-chromosome
      positive cells in the bone marrow mononuclear cells after culturing with CIK and
      DC-CIK was significantly lower than that after culturing with IL2 or LAK. Our
      results demonstrate that cytogenetics and FISH are useful techniques for the
      evaluation of the anti-CML effect of immune cells and that CIK or DC-CIK can be
      appropriate candidates for adoptive immune cell therapy in vivo or for leukemia
      cell purging ex vivo.

PMID- 11996792
TI  - Elevated frequency of ATM gene missense mutations in breast cancer relative to
      ethnically matched controls.
AB  - Studies of families of patients with ataxia telangiectasia (A-T) show an
      increased risk of breast cancer in heterozygous A-T carriers. However, expected
      increased levels of mutations in the ATM gene among unselected breast cancer
      patients have not been found to date. Previous methods of mutation detection were
      biased toward the detection of truncating mutations, and single nucleotide
      substitutions were likely to have been underreported. In this study, genomic DNA
      from 43 breast cancer patients and 43 control individuals were scanned for
      mutations in the entire ATM coding region (exons 4-65) and adjacent intronic
      splice regions (three megabases total) using detection of virtually all mutation
      single-strand conformation polymorphism (SSCP), a modification of SSCP with
      sufficient redundancy to detect virtually all mutations. Excluding a polymorphism
      found commonly in cases and controls, there were missense changes in 12 breast
      cancer patients, one of whom also had a protein truncating mutation, versus six
      controls (P=0.09). When all structural changes common to the cases and controls
      were excluded, missense or truncating changes were found in 10 cases compared to
      two in controls (P=0.013). The background of missense changes in controls is
      high. There is a trend towards elevation of all structural changes in cases, but
      the results are not statistically significant. Cohort-specific structural changes
      are significantly more prevalent in the breast cancer patients. The data are
      compatible with certain missense mutations in ATM predisposing to breast cancer.

PMID- 11996793
TI  - Evaluation of ETF1/eRF1, mapping to 5q31, as a candidate myeloid tumor suppressor
      gene.
AB  - Interstitial deletion of the long arm of chromosome 5 is a recurrent abnormality,
      mainly associated with myelodysplastic syndromes (MDS) and acute myeloid leukemia
      (AML), and it has been proposed therefore that the deleted region may contain a
      myeloid tumor suppressor gene. We have recently mapped a human translation
      termination factor gene, ETF1, to band 5q31 at D5S500, and thus to the smallest
      commonly deleted segment. We have evaluated ETF1 as a candidate myeloid tumor
      suppressor gene by analysis of the human acute myeloid leukemia cell line HL60,
      and of patients suffering from malignant myeloid diseases with cytogenetically
      defined abnormalities of chromosome 5. Fluorescence in situ hybridization
      analysis revealed hemizygous loss of the ETF1 locus in HL60 cells and in four of
      five leukemic samples, but no inactivating mutations were identified by
      sequencing of the remaining ETF1 allele.

PMID- 11996794
TI  - Chromosome changes in sarcomatoid renal carcinomas are different from those in
      renal cell carcinomas.
AB  - Sarcomatoid renal carcinoma (SRC) is an uncommon and highly malignant renal tumor
      with sarcomatous morphology or with both sarcomatous and carcinomatous
      components. The tumors are generally referred to as dedifferentiated or
      transformed renal cell carcinomas (RCC). Information on their genomic changes is
      scarce. Data from a cytogenetic study of four cases of SRC are presented in this
      article. Combined with a few other cases from the literature, it appears that
      genomic changes in most cases of SRC have little in common with those
      characterizing conventional RCC. Sarcomatoid transformation thus may occur
      occasionally in RCC without the characteristic chromosome changes but also, and
      perhaps more frequently, in a subgroup of RCC without the characteristic
      chromosome changes.

PMID- 11996795
TI  - Numerical aberrations of chromosome 9 in bladder cancer. A possible prognostic
      marker for early tumor recurrence.
AB  - To investigate whether nonrandom aberrations of chromosomal numbers could predict
      tumor recurrence in patients with bladder cancer, archival urine cytology
      specimens (Giemsa-stained) from patients previously treated for transitional cell
      carcinoma of the urinary bladder were studied retrospectively by fluorescence in
      situ hybridization. A total of 48 patients (pTis, 6; pTa, 2: pT1, 32; and pT2-4,
      8) were consecutively enrolled in this study, and numerical aberrations of
      chromosomes 9 and 17 were investigated. Cytology was diagnosed as negative for
      malignancy in 18 patients and positive in 30 patients. Twenty-seven of the 48
      patients (56%) had one or more chromosomal aberrations. The frequency of
      numerical aberrations of chromosome 17 was correlated with increasing stage and
      grade, whereas loss of copies of chromosome 9 (monosomy) was frequently observed
      at a lower stage and grade. Chromosomal aberrations were detected in 9 (50%) of
      18 patients with negative or equivocal cytology (class I, II, or III) by the
      Papanicolaou classification. Of eight patients with negative or equivocal
      cytology who developed tumor recurrence, four (50%) showed monosomy 9 and one
      (14%) showed a numerical aberration of chromosome 17. All six patients who showed
      monosomy of chromosome 9 developed tumor recurrence within 12 months, whereas
      four of the nine patients who did not show monosomy of this chromosome developed
      recurrence within 12 months (P<0.05, Fisher test). These results suggest that
      monosomy of chromosome 9 might be a prognostic marker for early tumor recurrence
      in patients with negative or equivocal cytology specimens.

PMID- 11996796
TI  - Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes
      in a colon carcinoma from a patient with hereditary nonpolyposis colorectal
      cancer.
AB  - The majority of tumors from patients affected by hereditary nonpolyposis
      colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread
      microsatellite instability (MSI) and somatic mutations in repeated sequences in
      several cancer-associated genes. An inverse relationship between MSI and
      chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors
      are generally characterized by diploid or near-diploid cells with few or no
      chromosomal rearrangements. We have studied MSI, somatic mutations in repeat
      containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma
      from a patient with a germline MLH1 mutation. Mutations in coding repeats were
      assessed in 10 macroscopically separate areas of the primary tumor and in two
      lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4, and TGFBRII)
      showed a consistent lack of mutations, whereas others (BAX, Caspase-5 and IGFIIR)
      displayed alterations in some tumor regions but not in others. The tumor had DNA
      index 1.1-1.2 and a stable, aberrant karyotype with extra copies of chromosomes 7
      and 12 and the structural aberrations i(1q), der(20)t(8;20), and der(22)t(1;22).
      The finding of CIN, MSI, and somatic mutations in coding repeats in this tumor
      suggests that these phenomena may act together in HNPCC tumorigenesis.
      Furthermore, the observed intratumoral heterogeneity of mutations in coding
      repeats implies these changes occur late in tumorigenesis and, thus, probably
      play a role in tumor progression rather than initiation.

PMID- 11996797
TI  - New cytogenetic variant, insertion (15;17)(q22;q12q21), in an adolescent with
      acute promyelocytic leukemia.
AB  - We present the case of a 15-year-old female with acute promyelocytic leukemia and
      a new variant chromosome rearrangement identified as ins(15;17)(q22;q12q21) by
      conventional cytogenetic analysis. This finding was confirmed by fluorescence in
      situ hybridization using the PML-RARA DNA probe and whole chromosome paints 15
      and 17. A typical PML-RARA fusion transcript consistent with a breakpoint in
      intron 3 of the PML gene and intron 2 of the RARA gene was identified by reverse
      transcription polymerase chain reaction.

PMID- 11996798
TI  - Tetrasomy 21 as a sole chromosome abnormality in acute myeloid leukemia.
      fluorescence in situ hybridization and spectral karyotyping analyses.
AB  - We report a case of acute myeloid leukemia with tetrasomy 21 as the sole
      chromosome abnormality in a constitutionally normal patient. Tetrasomy 21 was
      observed at presentation, disappeared in remission, but reappeared in recurrence
      of the disease. Fluorescence in situ hybridization analysis using a probe
      specific for the AML1 gene showed four distinct signals in 82.4% and three
      signals in 10.8% of interphase nuclei, although conventional G-banding revealed
      tetrasomy 21 alone in mosaicism with normal karyotype. Spectral karyotyping
      further confirmed the presence of extra copies of chromosome 21. Tetrasomy 21 as
      the only anomaly is relatively rare in patients with hematologic disorders other
      than Down syndrome, and to our knowledge has been reported previously in only
      seven cases. In a review of the literature, tetrasomy 21 as the only anomaly may
      be associated with myeloid disorders, although simultaneous numeric abnormalities
      other than chromosome 21 have been reported in acute lymphoblastic leukemia with
      hyperdiploid karyotype.

PMID- 11996799
TI  - Characterization of a complex chromosome rearrangement involving 6q in a melanoma
      cell line by chromosome microdissection.
AB  - Deletion of 6q is one of the most frequent chromosomal alterations in human
      malignant melanoma. Recently, we used chromosome painting probes of 6p and 6q to
      study 21 melanoma cell lines. A reciprocal translocation between chromosomes 6q
      and 17p was detected in one cell line (UACC-930). Upon further characterization
      of the translocation marker using the micro fluorescence in situ hybridization
      (FISH) technique, a complex rearrangement including an inversion of 6q and a
      translocation between the inverted 6q and 17p,
      [der(6)inv(6)(q16q27)t(6;17)(q26;p13)], was detected. A yeast artificial
      chromosome (YAC) clone spanning the breakpoint at 6q16 was isolated by the FISH
      screen. Loss of one or more copies of the YAC clone was also detected in 10 of 12
      melanoma cell lines. This result implies that the YAC clone may contain a
      putative tumor suppressor gene related to the pathogenesis of malignant melanoma.
      Further characterizations of the breakpoint at 6q16 and molecular cloning
      breakpoints at 6q27 and 17p13 are in progress.

PMID- 11996800
TI  - Genome-wide survey for chromosomal imbalances in ganglioglioma using comparative
      genomic hybridization.
AB  - Ganglioglioma is a mixed neuronal and glial tumor first described by Perkin in
      1926. Because of its rare occurrence in the central nervous system, the
      pathogenesis of this neoplasm is still largely unknown. Previous studies of
      ganglioglioma mainly focused on histologic features, immunohistochemical
      analysis, clinical treatment, and patient outcome. Very few cytogenetic and
      molecular genetic studies have been reported on this neoplasm. To better
      understand the mechanism underlying the development of ganglioglioma, we
      performed comparative genomic hybridization analysis to investigate chromosomal
      imbalances across the entire genome in five cases of gangliogliomas. Loss of
      genetic material on the short arm of chromosome 9 was a common genetic alteration
      found in three of five cases. Overrepresentation of partial or the whole
      chromosome 7 was another recurrent chromosomal imbalance, confirmed by
      fluorescence in situ hybridization. Immunohistochemical analysis was performed;
      all five cases revealed no reaction or low expression for epidermal growth factor
      receptor antibody. Our study highlights chromosomal regions for further fine
      mapping and investigation of candidate tumor suppressor genes involved in the
      pathogenesis of ganglioglioma.

PMID- 11996801
TI  - Adrenal myelolipoma with translocation (3;21)(q25;p11).
AB  - Adrenal myelolipoma (ML) is a rare, benign, nonfunctioning tumor-like lesion
      composed of mature adipose tissue interspersed with bone marrow-like
      hematopoietic elements in various proportions. It occurs usually in adults and is
      frequently asymptomatic in about half of cases. The histogenesis of adrenal ML is
      not clear and this lesion has been found to be associated with endocrine
      disorders, other adrenal dysfunction and tumors, and hyperstimulation with
      adrenocorticotropic hormone. Specific chromosomal abnormalities, however, have
      not been observed in such cases. Herein, we report a typical case of adrenal ML
      found incidentally in a 26-year-old man. Conventional cytogenetic techniques
      demonstrated balanced translocation between bands 3q25 and 21p11 in 9 of 20
      metaphases analyzed in cultured tumor cells. To the best of our knowledge, this
      is the first reported case of adrenal ML showing chromosomal abnormality. This
      finding would indicate that adrenal ML is a bona fide neoplasm and the
      possibility of derivation from misplaced hematopoietic cells may be alternatively
      taken into consideration in view of the similar genetic changes in hematopolietic
      neoplasms.

PMID- 11996802
TI  - Trisomy 10 and acute myeloid leukemia.
AB  - We report the second case of trisomy 10 as the sole abnormality in acute
      erythroblastic leukemia (AML M6). Trisomy 10 is a rare recurring numerical
      chromosomal abnormality is probably linked to a myeloblast subset with CD7+ and
      CD33+ immunophenotype. Most of the 15 cases reported to date in the literature
      have been M0, M1, or M2, with one showing AML M6 morphology.

PMID- 11996803
TI  - Acquired gain of an X chromosome as the sole abnormality in the blast crisis of
      chronic neutrophilic leukemia.
AB  - Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder
      characterized by sustained neutrophilic leukocytosis and absence of the
      Philadelphia chromosome. Most patients with CNL have normal karyotypes, and no
      specific cytogenetic abnormality has been identified. We report here a patient
      with CNL that evolved to myeloid blast crisis. A 73-year-old man was admitted to
      the hospital because of marked leukocytosis (leukocyte count 112.5 x 10(9)/L with
      91% segmented neutrophils) and massive hepatosplenomegaly that was diagnosed as
      CNL with a normal karyotype. After treatment with hydroxyurea for 7 months, the
      disease progressed to a blast crisis. Bone marrow showed myeloid hyperplasia with
      21% myeloblasts, 15% promyelocytes, and marked dysplastic changes of neutrophils.
      Blastic cells were positive for CD10, CD13, CD14, CD33, CD34, and HLA-DR.
      Chromosome analysis of the bone marrow cells showed 46,XY,+X in all 20 metaphase
      spreads. We reviewed 15 cases of CNL terminating in the blast crisis and
      confirmed that all cases transformed into myeloid crises and had poor prognoses.
      Furthermore, to our knowledge, this is the first case showing the acquired gain
      of an extra X chromosome as a sole abnormality in CNL. The gain of an extra X
      chromosome may play an important role in the progression from chronic phase to
      the blast crisis of CNL.

PMID- 11996804
TI  - Translocation (1;19)(q21;q13.3) is a recurrent reciprocal translocation in
      meningioma.
AB  - Benign meningiomas are characterized by a normal karyotype or loss of all or part
      of chromosome 22. Histologically higher grade tumors are typically characterized
      by a pattern of increasing chromosome loss and instability. This characteristic
      pattern of unbalanced chromosome aberrations is punctuated in the literature by
      several intriguing reports of a reciprocal t(1;19)(q21;q13.3) as the sole
      cytogenetic aberration. We report a third case showing the t(1;19)(q21;q13.3)
      with additional unstable secondary aberrations of a dic(18;22)(p11;p11) and
      telomeric fusions.

PMID- 11996805
TI  - Amperometric biosensors for detection of the prostate cancer marker (PSA).
AB  - Prostate specific antigen (PSA) has been identified as the most reliable clinical
      tool for diagnosing and monitoring prostate cancer (CAP). Since, there is no
      curative therapy available for prostate cancer, detecting the disease at the
      early stage is the best hope of increasing mortality rate. There are some
      procedures available for the detection of prostate cancer e.g. Tandem-R PSA,
      Hybritech Inc. (USA), IMx-PSA Abbott Laboratories (USA). However, these are time
      consuming and costly. We have developed a very simple and cost effective
      technique for identification and monitoring of prostate cancer using amperometric
      immunosensor. PSA is a glycoprotein with 93% peptide and 7% sugar content and
      isoelectric pH of 6.9. It may exist in the human serum as free (f-PSA) and
      complex (PSA-ACT) forms. Normally if the total PSA (t-PSA) level is more than 10
      ng/ml, CAP is suspected. This paper presents an amperometric detection procedure
      for t-PSA using three electrode system in which working electrode (WE) is made of
      hydroxyethyl cellulose (HEC) and rhodinised carbon. The method used is rapid,
      very easy to use and involves low cost compared with other procedures. The
      electrochemical response was directly observed due to enzymatic reaction via a
      sandwich immunoassay on the WE. Monoclonal capture antibody (Mab) to PSA was
      immobilised on the WE and the other Mab labelled by the enzyme marker,
      horseradish peroxidase (HRP), was used as a tracer antibody.

PMID- 11996806
TI  - A comparative study of plasma concentrations of liposomal amphotericin B (L-AMP
      LRC-1) in adults, children and neonates.
AB  - Amphotericin B (AmpB) incorporated into small unilamellar liposomes prepared from
      soya phosphatidylcholine and cholesterol (L-AMP-LRC-1) has been shown to be safe
      and effective in patients with systemic fungal infections. In this report, we
      compared the plasma levels of AmpB in adults, children and neonates following
      administration of L-AMP-LRC-1. A 1.0 mg/kg dose of L-AMP-LRC-1 in adult patients
      resulted in peak concentrations of 1.02+/-0.14 mg/l (mean+/-S.D.) on day 1, which
      increased to 1.66+/-0.19 mg/l on day 28 after continued therapy. The area under
      the plasma concentration-time curve also increased from 13.05+/-1.52 on day 1 to
      19.85+/-5.41 mg h/l on day 28. In children, the peak plasma concentration
      following 1.0 mg/kg per day dose of L-AMP-LRC-1 increased from 0.63+/-0.20 on day
      1 to 1.10+/-0.53 mg/l on day 28. While in neonates, the levels increased from
      0.54+/-0.17 on day 1 to 0.73+/-0.29 mg/l on day 28. These levels of AmpB in
      children and neonates were found to be significantly lower than in adults. This
      may be due to higher volume of distribution, since 1.0 mg/kg per day dose of L
      AMP-LRC-1 was found to be effective in neonates.

PMID- 11996807
TI  - A study of single drug particle adhesion interactions using atomic force
      microscopy.
AB  - This paper aims to use Atomic Force Microscopy (AFM) to characterise the
      interaction forces between micronized salbutamol particles, an active ingredient
      frequently used in metered dose inhalers, and also to glass, lactose and a
      fluoropolymer. The methodology used involves challenging a salbutamol
      functionalized AFM tip to the surfaces of interest and measuring the force
      experienced by the cantilever as a function of tip-sample separation. Analysis of
      this force-distance data allows quantification of the particle-substrate
      adhesion. This study yields a ranking of adhesion as
      glass>lactose>salbutamol>polytetrafluoroethylene (PTFE). An increase in the
      interaction force between the salbutamol particle and PTFE on repeated contact
      due to tribocharging is also observed.

PMID- 11996808
TI  - Dissolution kinetics of paracetamol single crystals.
AB  - The dissolution anisotropy of paracetamol crystals grown in the presence and
      absence of the molecularly similar additive, p-acetoxyacetanilide (PAA) was
      studied under controlled conditions using a single crystal dissolution method in
      undersaturated aqueous solutions. Linear dissolution rates were determined for
      all the major habit faces by measuring their movement (regression) with time in a
      flow cell using a microscope. The rates of dissolution of particular faces of the
      pure material were distinctly different in crystals of different morphology grown
      at different supersaturations. The dissolution rates of [001] and [110] faces of
      crystals grown in the presence of PAA (6.02% w/w in solution) are higher than
      those of pure paracetamol. The results correlate with the distribution of strain
      in the crystal and support the concept that integral strain increases the
      solubility and hence the dissolution rate of the material. The mechanism of the
      dissolution process at the [001], [201;] and [110] faces was defined using
      optical microscopy and X-ray topography. At all undersaturations above 1% the
      dissolution studies yielded well developed, structurally oriented, etch pits on
      both [001] and [201;] faces while on the [110] face rough shallow etch pits were
      observed. On all three faces, this etch-pitting was considerably more widespread
      than the dislocation content of the sector and probably reflects a 2-dimensional
      nucleation process rather than a dislocation controlled mechanism.

PMID- 11996809
TI  - Role of sphingosine synthesis inhibition in transcutaneous delivery of levodopa.
AB  - The present study was designed to investigate the role of skin sphingosine
      synthesis inhibition in enhancing the in vitro permeation of levodopa (LD), a
      hydrophilic drug, across rat skin. beta-Chloroalanine (beta-CA), a selective
      inhibitor of serine palmitoyl transferase was used for inhibiting sphingosine
      synthesis in viable skin. The sphingosine content in viable skin perturbed by
      acetone treatment and immediately treated with beta-CA (600 or 1200 microg/7
      cm(2)) was significantly less than that of perturbed viable skin after 36 h of
      treatment (P<0.001). The in vitro permeation of LD across perturbed-beta-CA
      treated skin was significantly greater than that across perturbed skin (P<0.001).
      This indicates an inverse relationship between in vitro permeation of LD and skin
      sphingosine content. The systemic delivery of percutaneously applied LD across
      normal rat skin was negligible. Higher C(max), lower T(max) and maintenance of
      effective plasma concentration of LD over 28 h was achieved by a single topical
      application of carbidopa-LD combination (1:4) to perturbed-beta-CA treated skin.
      Hence, skin sphingosine synthesis inhibition can be used as a novel means of
      enhancing systemic delivery of LD.

PMID- 11996810
TI  - Influence of different chitosan salts on the release of sodium diclofenac in
      colon-specific delivery.
AB  - Chitosan (CH) was dissolved in aqueous solutions containing aspartic, glutamic,
      hydrochloric, lactic and citric acids to obtain different chitosan salts.
      Chitosan salts were collected from the solutions by spray-drying and the powders
      obtained were mixed with Sodium Diclofenac (SD), taken as a model anti
      inflammatory drug. This study evaluated in vitro the influence of acid type on
      the release behaviour of SD from the physical mixture during gastrointestinal
      transit. The physical mixture of the chitosan salts with SD provided slower drug
      release than the pure drug both in acidic and alkaline pHs. In addition, the
      interaction with beta-glucosidase at pH 7.0 enhanced the release rate. Among the
      CH salts used, glutamic and aspartic salts provided the best control of release.

PMID- 11996811
TI  - The influence of liquid binder on the liquid mobility and preparation of
      spherical granules by the process of extrusion/spheronization.
AB  - The influence of the type of liquid on the movement of water and the performance
      of the preparation of pellets by the process of extrusion/spheronization has been
      studied. Liquid movement was assessed by a pressure membrane technique and by
      extrusion, while the pellet properties were assessed in the terms of their median
      size, size range (interquartile range), roundness (by a two-dimensional shape
      factor) and porosity. The model formulations studied were microcrystalline
      cellulose (MCC) and mixtures of MCC and barium sulphate at 20, 50 and 80% levels.
      The liquids were water, a 25% solution of glycerol in water and an anionic
      surfactant (sodium lauryl sulphate) below its c.m.c. and two concentrations (0.01
      and 0.0001%) of a non-ionic surfactant (Pluronic PF68). The presence of the
      different liquids changed the ease and extent with which the liquid could be
      removed (drying) and reabsorbed (wetting), resulting in lower levels of
      saturation with the glycerol solution and considerably increased levels of
      saturation with the surfactants. Changes in liquid movement during extrusion,
      were influenced more by the level of liquid and the rate of extrusion, than by
      its composition. The level of liquid was also an important factor in terms of the
      force necessary to extrude the different formulations. For a given level of
      liquid, the glycerol solution tended to increase extrusion force, while the
      surfactant solutions tended to decrease the extrusion force. The liquid levels,
      particulate composition and rate of extrusion were important in terms of pellet
      size, size range, roundness and porosity. The low level of liquid involved
      produced elongated pellets. The wet formulations produced larger, agglomerated
      pellets with a wide particle size range and a higher porosity. The lowest
      porosity pellets were prepared from mixtures with no or a low barium sulphate
      content while the highest levels of porosity were found with equal parts MCC and
      barium sulphate. In general, for equivalent liquid contents, pellets made with
      the glycerol solution were more porous than those prepared with water while the
      opposite was true for pellets made with surfactants. Although the different
      liquids influenced water movements, they did not prevent the formation of high
      quality pellets by the process of extrusion/spheronization.

PMID- 11996812
TI  - Biocompatible stabilizers in the preparation of PLGA nanoparticles: a factorial
      design study.
AB  - Poly(lactic-co-glycolic-acid) nanoparticles are often produced using the w/o/w
      emulsification solvent evaporation method. In most cases poly(vinyl alcohol)
      (PVA) is used as stabilizer of the emulsion. The goal of this study was to
      compare a series of polymers to PVA in a 2(2) full factorial design study. The
      influence of the concentration of PVA and the polymers tested on particle size
      and zeta potential value was evaluated before and after freeze-drying of the
      prepared particles. Nanoparticles were obtained with most polymers when they were
      used in combination with PVA. Leaving PVA out of the formulation, however,
      increased the size of the particles over 1 microm. Two exceptions are poloxamer
      and carbopol, which can be considered as valuable alternatives to PVA. Zeta
      potential values were usually slightly negative, the most extreme zeta potential
      values were measured when poloxamer and carbopol were employed. The use of
      gelatin type A made it possible to achieve positive values. The original 2(2)
      full factorial design study was further expanded to a central composite design
      for poloxamer and carbopol, in order to fit the measured data to a quadratic
      model and to calculate response surfaces.

PMID- 11996813
TI  - Buccoadhesive erodible disk for treatment of oro-dental infections: design and
      characterisation.
AB  - Buccoadhesive erodible disks of cetylpyridinium chloride were prepared using
      different bioadhesive polymers along with excipients like mannitol. The purpose
      of designing the erodible disk was to obviate the need for removal of exhausted
      device. The optimized disk containing 5.0 mg of cetylpyridinium chloride, 2.0 mg
      of magnesium stearate and 6.0 mg of mannitol along with sodium carboxy methyl
      cellulose DVP and hydroxypropylmethylcellulose K4M in the ratio of 1:3 was found
      to release the drug for a period of over 6.0 h without getting dislodged. Maximum
      in vitro drug release was found to be 94.78% in 6.0-h study. In situ release
      characteristics were evaluated using a 'flow-through assembly', which simulated
      the conditions of the human buccal cavity. The drug concentrations in the in situ
      samples were found to be above minimum inhibitory concentration (MIC) of the
      drug. The bioadhesive performance and the surface pH of the disks were
      satisfactory. Cetylpyridinium chloride disks were tested against microorganisms
      commonly found in oro-dental infections namely Candida albicans, Staphylococcus
      aureus, Escherichia coli and Streptococcus mutans. The disk as well as the in
      situ samples showed inhibition of growth of microorganisms. Approval was taken
      from Jamia Hamdard Review Board (Ethical Board) to perform in vivo studies in
      healthy human volunteers. In vivo evaluation of buccoadhesive disks revealed
      adequate comfort, taste, and non-irritation and none of the volunteers reported
      severe dry mouth/severe salivation or heaviness at the place of attachment.
      Salivary concentrations were maintained above MIC for 8.0 h. Correlation was
      found between the drug concentration in situ and concentration of drug in saliva
      collected in healthy human volunteers. The correlation was found to be positive
      with a correlation coefficient of 0.9596. It was found to be statistically
      significant at 5% confidence level (P<0.05).

PMID- 11996814
TI  - Quantitative structure-permeability relationships for percutaneous absorption: re
      analysis of steroid data.
AB  - Certain molecules, in particular steroids, have been observed to be outliers to
      quantitative structure-permeability relationships (QSPRs) for skin permeability
      (k(p)). Recently, however, many of the historical skin permeability data for
      these compounds have been found not to be consistent with more modern data. In
      this study QSPRs were re-analysed replacing the originally published steroid
      permeability data with those from more recent studies. A highly significant QSPR
      describing skin permeability in terms of the octanol-water partition coefficient
      (logP) and molecular weight (MW) was derived (log k(p)=0.74 logP-0.0091MW-2.39).
      This model is similar to those published previously. Statistical analysis of the
      residuals from the QSPR determined that the steroids are no longer outliers to
      this model. Thus, they may be considered to penetrate the skin by the same means
      as the majority of exogenous chemicals in this model.

PMID- 11996815
TI  - Efficacy of BCNU and paclitaxel loaded subcutaneous implants in the interstitial
      chemotherapy of U-87 MG human glioblastoma xenografts.
AB  - Nude mice were challenged with human U-87 MG glioblastoma tumors to assess the
      efficacy of different cytostatics and different application protocols. While the
      intraperitoneal application of BCNU solutions (3 times 20 mg BCNU/kg) had no
      effect on tumor growth, the application of polymer matrices made of a physical
      mixture of poly(1,3-bis[carboxyphenoxpropane]-co-sebacic acid) 20:80 with
      poly(D,L-lactic-co-glycolic acid) loaded with 0.25 mg BCNU, slowed down the
      growth of tumors significantly. When the animals were treated with implants
      carrying 0.25 mg BCNU they responded to the treatment whether the tumor had been
      inoculated recently (9 days ago) or whether it was fully established (after 20
      days). After its sensitivity was proven, the xenograft model was used to further
      investigate the efficacy of anticancer drugs and some treatment regimens using
      polymer implants. Thus the tumor model allowed to discriminate between the
      efficacy of different doses of BCNU. Only implants loaded with 0.75 or 1 mg of
      BCNU led to a substantial suppression of tumor growth over approximately 2
      months. While BCNU was only able to suppress the growth of the tumor, the
      combination of BCNU with paclitaxel led to a complete remission in some animals.
      These preliminary results suggest that combinations of cytostatics might improve
      local chemotherapy of malignant glioma substantially. Based on our data it will
      be worthwhile to investigate implants that release drugs such as BCNU and
      paclitaxel closer. Amongst other factors we will try to elucidate the effect of
      repetitive doses of drugs using programmable implants.

PMID- 11996816
TI  - An in vitro mucosal model for prediction of the bioadhesion of alginate solutions
      to the oesophagus.
AB  - This paper discusses the development of an in vitro model utilised to assess the
      adhesion of alginate solutions to porcine oesophageal tissue. The methodology
      involved the construction of retention apparatus onto which sections of tissue
      were mounted. Fluorescently labelled alginate solutions of known rheological
      profile were dispensed onto the tissue at a concentration of 2% w/v. A washing
      solution was applied at a specified rate to mimic saliva flow and the eluted
      material collected. Fluorimetric analysis allowed dose retention to be assessed
      as a function of time. The effect of the nature of the washing solution and the
      choice of alginate were investigated. It was found that after 30 min up to 20% of
      the applied alginate dose remained associated with the tissue, regardless of the
      alginate selected from the range examined. The nature of the washing medium did
      not have a significant effect on retention, irrespective of the inherent mucin
      concentration. Overall this study indicated that the technique presented offers a
      viable means of studying bioadhesion of liquids and also demonstrates that
      alginate solutions may have an application as bioadhesive agents for localisation
      within the oesophagus.

PMID- 11996817
TI  - Chronic administration of verapamil, ketoconazole and carbamazepine: impact on
      immunological parameters.
AB  - Inhibitors of P-glycoprotein (P-gp) (verapamil) or cytochrome P-450
      (ketoconazole) may reduce IL2 production and T lymphocyte proliferation in vitro.
      We have examined the effects of chronic oral administration of these drugs and of
      the cytochrome P450 inductor, carbamazepine, on the hematological and
      immunological parameters of mice. We found no changes after giving the mice 0.12
      mg verapamil, 0.85 mg ketoconazole, or 0.514 mg carbamazepine per mouse for 4
      weeks (5 days/week). But giving the drugs for an additional 7 weeks at 0.6 mg
      (verapamil), 4.25 mg (ketoconazole) or 2.57 mg/mouse (carbamazepine), resulted in
      significant decreases in monocytes in the verapamil treated group (-51%) and in
      CD4+ cells in the carbamazepine group (-35%). Chronic oral administration of
      these drugs reduced the lymphocyte counts of mice by 10-18% and their NK counts
      by 10-16%. These changes could be due to changes in P-gp function in the
      transport of IL2, with decreases caused by verapamil and ketoconazole.

PMID- 11996818
TI  - Study of effect of excipient source variation on rheological behavior of
      diltiazem HCl-HPMC wet masses using a mixer torque rheometer.
AB  - In the wet massing of powders and powder blends, the rheological behavior of the
      wet powder masses not only plays a critical role in the unit process but also
      influences the attributes of the product. The physical properties of the powder
      excipients, such as particle size and size distribution, shape, surface area,
      bulk and tapped density and surface morphology, are a major source of variability
      in the rheological behavior of wet powder masses and the quality attributes of
      the final product. The objective of the present investigations was to study the
      rheological behavior of wet masses containing hydroxypropyl methylcellulose
      (HPMC) obtained from two sources (Methocel from Dow and Pharmacoat from Shin
      Etsu) using a mixer torque rheometer. In order to simulate a real formulation,
      diltiazem HCl (DTZ) (40% loading) was used as part of the substrate powder mass.
      Hydroxypropyl cellulose (HPC) was used as the binder. Since HPMC is water
      soluble, isopropyl alcohol (IPA) was used as the wet massing liquid. The
      rheological behavior of the wet powder masses was studied as a function of mixing
      time and amount of wet massing liquid (IPA). The rheological profiles obtained
      for DTZ-Methocel and DTZ-Pharmacoat exhibited same magnitude for mean torque,
      however, for DTZ-Pharmacoat the peak was more extended than that for DTZ
      Methocel. The extended peak for DTZ-Pharmacoat indicated that the wet mass will
      stay suitable during the process for larger quantities of the wet massing liquid
      before turning into paste and becoming unsuitable for the process as compared
      with the DTZ-Methocel system. The mixing kinetics of the two powder systems
      appeared to be quite different. These differences in the rheological behavior of
      the wet masses may be attributed to the difference in the particulate and surface
      properties of the two HPMCs. Some of the properties of the two HPMCs, such as
      particle size and size distribution, surface area, surface morphology and DSC
      thermograms, explain the difference observed in their rheological behavior. The
      difference in the rheological profiles of the two DTZ-HPMC systems indicated
      superiority of Pharmacoat over Methocel considering their wet massing behavior.

PMID- 11996819
TI  - Improvement of physicochemical properties of N-4472 part I formulation design by
      using self-microemulsifying system.
AB  - The optimization of oral dosage form formulation has been developed for N-4472, N
      [2-(3,5-di-tert-butyl-4-hydroxyphenethyl)-4,6-difluorophenyl]-N'-[4-(N
      benzylpiperidyl)] urea, which was a poorly water-soluble drug having a lipid
      lowering effect. Formulations that contained various surfactants and water
      soluble polymers were prepared and the solubility of N-4472 was evaluated in JP
      XIV first fluid (pH 1.2), JP XIV second fluid (pH 6.8), and distilled water. The
      highest solubility of N-4472 was achieved when L-ascorbic acid (VC), Gelucire
      44/14, and HCO-60 were used as additives. It was confirmed that this formulation
      could create microemulsion droplets with a mean droplet size of approximately 20
      nm and a sharp droplet distribution pattern in JP XIV first fluid, JP XIV second
      fluid, and distilled water. When JP XIV second fluid was used as a dissolution
      medium, however, an eventual decrease of solubility was observed, that is, the
      fluid became white and cloudy as time passed. It was found that the addition of
      sodium dodecyl sulfate (SDS) was effective to prevent the lowering of solubility,
      and that a weight ratio of 1.0/1.5/11.4/4.9/3.8 for N-4472/VC/Gelucire 44/14/HCO
      60/SDS was optimum for the self-microemulsifying formulation. It was assumed that
      electrostatic repulsion of microemulsion droplets and an increase of the cloud
      point by the addition of SDS were responsible for the successful formation of a
      stable microemulsion.

PMID- 11996820
TI  - Buccal absorption of ergotamine tartrate using the bioadhesive tablet system in
      guinea-pigs.
AB  - The buccal administration of ergotamine tartrate (ET) combined with polyvinyl
      alcohol (PVA) gel brought about higher plasma concentration of ET compared with
      that of oral administration of capsules in guinea-pigs. T(max) of ET in plasma of
      buccal administration was significantly smaller than that of oral administration.
      For the buccal dosage form of ET, the bioadhesive tablet system (BTS) was newly
      developed. It consisted of a reservoir of drug and an adhesive region. BTS showed
      better absorption of ET compared with PVA gel in guinea pigs. Among several
      pharmaceutical bases in the reservoir of BTS, Witepsol W-35 was most effective.
      It is likely that the high lipophilic property of Witepsol W-35 in which ET was
      dissolved facilitated the drug release by its relatively low melting point
      (around 35 degrees C), consequently a rapid absorption. In addition, the
      enhancing activity of the cod-liver oil extract (CLOE) in hydrophilic ointment on
      the in vivo buccal ET absorption was clarified to be comparable to that in the in
      vitro study utilizing the keratinized epithelial-free membrane (KEF-membrane) of
      the hamster cheek pouch.

PMID- 11996821
TI  - Effects of mixed polyethyleneglycol modification on fixed aqueous layer thickness
      and antitumor activity of doxorubicin containing liposome.
AB  - Polyethyleneglycol (PEG) has often been used for the modification of liposomes,
      but it is difficult to insert PEG on the surface of liposomes, and the effects of
      modification are not marked enough. In this study, we examined the fixed aqueous
      layer thickness (FALT) of single or mixed PEG (molecular weight, 340, 500, 900,
      2000)-modified doxorubicin (DOX) liposomes, and physical character and biological
      properties of these liposomes. On single PEG-modification, as the PEG-molecular
      weight increased, FALT also increased, but the ratio of the increase was reduced.
      While on modification by a mixture of PEG2000 and PEG with a short
      polyoxyethylene chain (PEG340 or PEG500), FALT increased compared with the single
      PEG2000-modified value. Moreover, when liposomes were modified by mixture of
      PEG2000 and PEG500, we recognized the most suitable mixed rate (PEG2000,
      500=2:1), showed the maximum FALT. On the other hand, in vivo, as increase of
      FALT, DOX concentrations increased in the plasma and in the tumor, decreased in
      the liver. Furthermore, liposomes with remarkable increase of FALT showed
      enhancement of antitumor activity. As a result, the connection among increase of
      FALT and improvement of circulation in blood, the involvement of antitumor
      activity of DOX of these liposomes was suggested.

PMID- 11996822
TI  - Pharmacokinetics of verapamil and its metabolite norverapamil from a buccal drug
      formulation.
AB  - Pharmacokinetics of verapamil and its metabolite norverapamil, from buccal drug
      formulation administered in a dose 20 mg in relation to conventional tablets of
      verapamil 40 mg, used in medical practice, was determined. Buccal formulation has
      previously been designed as an alternative form of dosing verapamil.
      Bioavailability was determined by a crossover method in 12 healthy volunteers.
      Drug concentration in plasma was determined by means of HPLC with a fluorescence
      detector. For buccal formulation the average values of C(max) and AUC(0-24 h) for
      verapamil were much higher than for the reference Staveran tablets and amounted
      to 51.28 and 320.23 ng/ml h, respectively. However, for norverapamil the
      corresponding values for buccal formulation were much lower than for a
      conventional tablet. It has been demonstrated that the proposed buccal verapamil
      dosing ensures different metabolism of the drug as compared to tablets. Better
      parameters of bioavailability of verapamil from buccal formulation of twice a
      smaller dose than that in the tablet, prove that this new drug might be form more
      effective clinically than the conventional one.

PMID- 11996823
TI  - Spray-dryed bupivacaine-loaded microspheres: in vitro evaluation and
      biopharmaceutics of bupivacaine following brachial plexus administration in
      sheep.
AB  - Microspheres could be used as a drug delivery system to prolong the duration of
      action of bupivacaine and to reduce its systemic absorption leading to high
      plasma concentrations related to central nervous and cardiovascular toxicity.
      Bupivacaine-loaded microspheres were made by spray-drying using polylactide-co
      glycolide polymers from different sources and with different bupivacaine-polymer
      ratio. The characterization of microspheres concerned the shape and size, the
      bupivacaine drug-content (DC) and the cumulative release profiles. We evaluated
      in sheep the bupivacaine pharmacokinetics: (i) after short intravenous infusion
      of 75 mg bupivacaine solution; and (ii) following brachial nerve plexus
      injections of 75 mg bupivacaine solution alone, with the addition of 75 microg
      epinephrine, with the addition of 150 microg epinephrine and of bupivacaine (750
      mg)-loaded microspheres. Release profiles showed a biphasic pattern whatever the
      DC. After i.v. infusion the mean clearance value was 1.53+/-0.53 l/min and the
      mean elimination half-life was 120.5+/-73.1 min. Following brachial plexus nerve
      injection, bupivacaine C(max) were lower than 100 ng/ml following either solution
      or microspheres administration. Ninety percent of the 75 mg bupivacaine given as
      a solution were absorbed in 5.8+/-1.0 h (bupivacaine alone) compared to 24.6+/
      1.2 h following microsphere administration.

PMID- 11996824
TI  - Intestinal paracellular permeation enhancement with quaternised chitosan: in situ
      and in vitro evaluation.
AB  - Previous studies have shown that N-trimethyl chitosan chloride (TMC) is a potent
      absorption enhancer for hydrophilic and macromolecular compounds across mucosal
      surfaces. TMC proved to be effective in neutral and basic pH environments where
      the absorption enhancing ability of chitosan is severely hampered by its
      insolubility in these environments. The absorption enhancing characteristics of
      TMC polymers with different degrees of quaternisation were investigated in vitro
      and in situ to identify the most effective polymer in a neutral pH environment.
      Different degrees of quaternisation were obtained by varying the number and
      duration of the reaction steps in the synthesis process of TMC. The TMC polymers
      were characterised with 1H-NMR spectroscopy and the degrees of quaternisation
      were between 22.1 and 48.8%. Everted intestinal sacs (rats) were used to
      determine the effect of the polymers (0.0625-0.5% w/v) on the permeation of the
      hydrophilic model compound, [14C]mannitol, at a pH value of 7.4. A single pass
      intestinal perfusion method was also used to evaluate the permeation enhancing
      properties of the TMC polymers under the same conditions. The results obtained
      from both methods clearly showed a pronounced enhancement of [14C]mannitol
      permeation when administered with the different TMC polymers. It was shown that
      the permeation enhancing effects depend on the degree of quaternisation of TMC.
      In both models the best permeation enhancing results were obtained with the
      highest degree of quaternisation of TMC (48.8%) at a concentration of 0.5% w/v.

PMID- 11996825
TI  - Polymorphism of the CNS active drug Org 13011: the application of high
      temperature analysis to detect new polymorphs.
AB  - The polymorphism of the CNS active compound Org 13011 was studied using different
      crystallisation methods (i.e. different solvents and cooling rates). The samples
      were analysed by Raman, solid state NMR, X-ray powder diffraction (XRPD) and
      thermal analysis. This led to the characterisation of two crystalline forms A and
      B. Further high temperature analysis using Raman, XRPD, solid state NMR and DSC
      revealed another two (high temperature) crystalline forms C and D. The
      transitions to the high temperature crystalline forms occur at temperatures of
      about 60 degrees C. This study shows that the application of high temperature
      experiments is useful and can lead to the discovery of new crystalline forms.

PMID- 11996826
TI  - Coating of cationized protein on engineered nanoparticles results in enhanced
      immune responses.
AB  - A significant emphasis has been placed on the development of improved adjuvants
      and delivery systems to improve both antibody production and cell-mediated
      immunity. The overall goal of this project was to cationize a model protein
      antigen, beta-galactosidase (nGal), coat the cationized Gal (cGal) on the surface
      of novel anionic nanoparticles engineered from microemulsion precursors, and
      assess the immune response of this system after subcutaneous injection to mice.
      Gal was chemically cationized as evidenced by gel electrophoresis. The cGal was
      coated on anionic nanoparticles (78+/-11 nm) engineered from oil-in-water
      microemulsion precursors to produce cGal-coated nanoparticles. The immune
      response to nGal with 'Alum', cGal alone, and cGal-coated nanoparticles were
      assessed after subcutaneous injection to Balb/c mice. cGal alone elicited similar
      antibody titer to nGal with 'Alum'. However, cGal-coated nanoparticles elicited
      the strongest and most reproducible antibody titer. cGal alone produced very high
      levels of Th1 cytokines, but low levels of Th2 cytokines. In contrast, cGal
      coated nanoparticles significantly enhanced both the Th1 and Th2 cytokines. The
      results demonstrated the utility of antigen-coated nanoparticles to enhance both
      the humoral and Th1-type immune responses, in parallel.

PMID- 11996827
TI  - Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin.
AB  - Aim of this study was to evaluate solid lipid nanoparticles (SLN) as carriers for
      topical ocular delivery of tobramycin (TOB). The SLN were in the colloidal size
      range (average diameter below 100 nm; polydispersity index below 0.2) and
      contained 2.5% TOB as ion-pair complex with hexadecyl phosphate. The preocular
      retention of SLN in rabbit eyes was tested using drug-free, fluorescent SLN (F
      SLN): these were retained for longer times on the corneal surface and in the
      conjunctival sac when compared with an aqueous fluorescent solution. A suspension
      of TOB-loaded SLN (TOB-SLN) containing 0.3% w/v TOB was administered topically to
      rabbits, and the aqueous humour concentration of TOB was determined up to six
      hours. When compared with an equal dose of TOB administered by standard
      commercial eyedrops, TOB-SLN produced a significantly higher TOB bioavailability
      in the aqueous humour.

PMID- 11996828
TI  - Characterization of human nasal primary culture systems to investigate peptide
      metabolism.
AB  - The objectives of this study were to validate and compare the suitability of
      different primary cell culture systems as models to investigate peptide enzymatic
      stability following nasal administration. The degradation kinetics of a model
      peptide, leucine enkephalin (Tyr-Gly-Gly-Phe-Leu, Leu-Enk), was determined in
      four nasal cell culture systems: immersion, air-liquid interface, sequential
      monolayer-suspension, floating collagen. The influence of enzyme inhibitors
      (bestatin, puromycin) and Leu-Enk metabolite analogs (Tyr-Gly, Phe-Leu, Tyr-Gly
      Gly, Gly-Phe-Leu) on the Leu-Enk degradation profile was also investigated. The
      disappearance of Leu-Enk in all the cell culture systems followed first order
      kinetics. The specific activity in the cell culture systems followed the rank:
      sequential monolayer-suspension (32.60 microM min(-1) mg(-1)) >air-liquid
      interface (15.19 microM min(-1) mg(-1)) >immersion (11.49 microM min(-1) mg(-1))
      >floating collagen (4.57 microM min(-1) mg(-1)). At equimolar concentration,
      bestatin had a higher inhibitory effect than puromycin. The rate of hydrolysis of
      Leu-Enk was reduced significantly by co-incubation with Leu-Enk metabolite
      analogs. This study showed that immersion, sequential monolayer-suspension and
      air-liquid interface culture systems may be potentially suitable for further
      studies on peptide enzymatic stability following nasal administration.

PMID- 11996829
TI  - Reverse water-in-fluorocarbon emulsions for use in pressurized metered-dose
      inhalers containing hydrofluoroalkane propellants.
AB  - Pulmonary administration of drugs has demonstrated numerous advantages in the
      treatment of pulmonary diseases due to direct targeting to the respiratory tract.
      It enables avoiding the first pass effect, reduces the amount of drugs
      administered, targets drugs to specific sites and reduces their side effects.
      Reverse water-in-fluorocarbon (FC) emulsions are potential drug delivery systems
      for pulmonary administration using pressurized metered-dose inhalers (pMDI). The
      external phase of these emulsions consists of perfluorooctyl bromide (PFOB,
      perflubron), whereas their internal phase contains the drugs solubilized or
      dispersed in water. These emulsions are stabilized by a perfluoroalkylated
      dimorpholinophosphate (F8H11DMP), i.e. a fluorinated surfactant. This study
      demonstrates the possibility of delivering a reverse fluorocarbon emulsion via
      the pulmonary route using a CFC-free pMDI. Two hydrofluoroalkanes (HFAs)
      (Solkane(R) 134a and Solkane(R) 227) were used as propellants, and various
      solution (or emulsion)/propellant ratios (1/3, 1/2, 2/3, 1/1, 3/2, 3/1 v/v) were
      investigated. The insolubility of water (with or without the fluorinated
      surfactant F8H11DMP) in both HFA 227 and HFA 134a was demonstrated. PFOB and the
      reverse emulsion were totally soluble or dispersible in all proportions in both
      propellants. This study demonstrated also that the reverse FC emulsion can be
      successfully used to deliver caffeine in a homogeneous and reproducible way. The
      mean diameter of the emulsion water droplets in the pressured canister was
      investigated immediately after packaging and after 1 week of storage at room
      temperature. Best results were obtained with emulsion/propellant ratios comprised
      between 2/3 and 3/2, and with HFA 227 as propellant.

PMID- 11996830
TI  - The core structure of the lipopolysaccharide from the causative agent of plague,
      Yersinia pestis.
AB  - The rough-type lipopolysaccharide (LPS) of the plague pathogen, Yersinia pestis,
      was studied after mild-acid and strong-alkaline degradations by chemical
      analyses, NMR spectroscopy and electrospray-ionization mass spectrometry, and the
      following structure of the core region was determined:where L-alpha-D-Hep stands
      for L-glycero-alpha-D-manno-heptose, Sug1 for either 3-deoxy-alpha-D-manno-oct-2
      ulosonic acid (alpha-Kdo) or D-glycero-alpha-D-talo-oct-2-ulosonic acid (alpha
      Ko), and Sug2 for either beta-D-galactose or D-glycero-alpha-D-manno-heptose. A
      minority of the LPS molecules lacks GlcNAc.

PMID- 11996831
TI  - Base catalysed isomerisation of aldoses of the arabino and lyxo series in the
      presence of aluminate.
AB  - Base-catalysed isomerisation of aldoses of the arabino and lyxo series in
      aluminate solution has been investigated. L-Arabinose and D-galactose give L
      erythro-2-pentulose (L-ribulose) and D-lyxo-2-hexulose (D-tagatose),
      respectively, in good yields, whereas lower reactivity is observed for 6-deoxy-D
      galactose (D-fucose). From D-lyxose, D-mannose and 6-deoxy-L-mannose (L-rhamnose)
      are obtained mixtures of ketoses and C-2 epimeric aldoses. Small amounts of the 3
      epimers of the ketoses were also formed. 6-Deoxy-L-arabino-2-hexulose (6-deoxy-L
      fructose) and 6-deoxy-L-glucose (L-quinovose) were formed in low yields from 6
      deoxy-L-mannose and isolated as their O-isopropylidene derivatives. Explanations
      of the differences in reactivity and course of the reaction have been suggested
      on the basis of steric effects.

PMID- 11996832
TI  - Synthesis and X-ray structures of sulfate esters of fructose and its
      isopropylidene derivatives. Part 1: 2,3:4,5-di-O-isopropylidene-beta-D
      fructopyranose 1-sulfate and 4,5-O-isopropylidene-beta-D-fructopyranose 1
      sulfate.
AB  - 2,3:4,5-Di-O-isopropylidene-beta-D-fructopyranose 1-sulfate have been synthesized
      by treatment of 2,3:4,5-di-O-isopropylidene-beta-D-fructopyranose with pyridine
      sulfur trioxide complex. Direct hydrolysis of the isopropylidene group at C-4, C
      5 gave 2,3-O-isopropylidene-beta-D-fructopyranose 1-sulfate. The crystal and
      molecular structures of ammonium (1a) and potassium (1b) salts of
      diisopropylidene derivative and ammonium (2) salt of monoisopropylidene
      derivative were determined by X-ray crystallography. Data for 1a and 1b were
      collected in 120 K and in 150 K for 2. All salts crystallized in P2(1)2(1)2(1)
      space group. There are three independent anions in asymmetric unit in 1b.
      Pyranose rings in the diisopropylidene derivative salts studied adopt 2S(0) twist
      boat conformation, whereas in the monoisopropylidene exists in a slightly
      distorted chair conformation (4C(1)). A staggered conformation is preferred by
      the sulfate group as indicated by values of C-(ester)-S-O(terminal) torsion
      angles: -173.2(4) degrees in 1a, 175.1(6) degrees in anion A of 1b, 170.8(6)
      degrees in anion C of 1b and 177.9(2) degrees in 2. However, strong interactions
      such as potassium-oxygen and H-bonds may affect the geometry: in anion B of 1b
      the value of the torsion angle is 139.4(6) degrees.

PMID- 11996833
TI  - Studies on the glycosylation of wild-type and mutant forms of Aspergillus niger
      pectin methylesterase.
AB  - Pectin methylesterase (PME) is one of a number of enzymes released by the fungus
      Aspergillus niger that are involved in the degradation of specific plant cell
      wall structures. PME is a glycoprotein with three potential sites for N-linked
      glycosylation. The glycosylation may affect the hydrolytic activity or the
      substrate specificity of PME. In this work, we investigate first the structures
      and the attachment sites of the glycans present on recombinant wild-type PME.
      Further, a series of PME mutants was created in which the three potential N
      linked glycosylation sites were eliminated in all possible combinations. The
      glycosylation of the mutants and their activities were then studied. Mass
      spectrometric techniques tailored for carbohydrate analysis were applied to both
      characterize the glycan structures and to determine the specific sites of
      attachment. High mannose structures with variable numbers of mannose were found
      on the wild-type, as well as the mutant forms. Studies using the mutants suggest
      that glycosylation does not strongly influence the activity. Whether it may
      affect the substrate specify of the enzyme is unknown, and that aspect will be
      explored in future work.

PMID- 11996834
TI  - Structure of the O-polysaccharide from the lipopolysaccharide from Vibrio
      cholerae O6.
AB  - The O-polysaccharide from Vibrio cholerae O6 was isolated from the LPS by mild
      acid hydrolysis and has been investigated by sugar and methylation analysis and
      NMR spectroscopy. The polysaccharide was also depolymerized with aqueous
      hydrofluoric acid to give the repeating unit and multiples thereof. The O
      polysaccharide had the following tetrasaccharide repeating unit. Two O-acetyl
      groups are present, one of them making the GlcNAc residue fully substituted and
      the steric crowding considerable at the branching residue.

PMID- 11996835
TI  - Isolation of oligosaccharides from a partial-acid hydrolysate of pneumococcal
      type 3 polysaccharide for use in conjugate vaccines.
AB  - A series of well-defined oligosaccharide fragments of the capsular polysaccharide
      of Streptococcus pneumoniae type 3 has been generated. Partial-acid hydrolysis of
      the capsular polysaccharide, followed by fractionation of the oligosaccharide
      mixture by Sepharose Q ion-exchange chromatography yielded fragments containing
      one to seven [-->3)-beta-D-GlcpA-(1-->4)-beta-D-Glcp-(1-->] repeating units. The
      isolated fragments were analysed for purity by high-pH anion-exchange
      chromatography with pulsed amperometric detection (HPAEC-PAD) using an IonPac
      AS11 column, and their structures were verified by 1H NMR spectroscopy and nano
      electrospray mass spectrometry. The oligosaccharides can be used to produce
      neoglycoprotein vaccines with a defined carbohydrate part.

PMID- 11996836
TI  - Structural relaxation and physical ageing of starchy materials.
AB  - The structural relaxation during the ageing of an amorphous maltose and a starch
      sorbitol mixture was examined using a range of physical techniques. Heat
      capacity, measured by differential scanning calorimetry, showed an overshoot in
      the glass-transition region, the size of which was temperature and time
      dependent. Volume relaxation measurements were made at different ageing
      temperatures in the range T(g) -15 to -30 K. The volume decreased with increasing
      ageing time, in an essentially linear fashion with log time. The mechanical
      behaviour of the materials showed a progressive embrittlement on ageing. For both
      materials, the mechanical relaxation time increased with ageing, and the material
      became stiffer. Investigation of the effect of physical ageing on transport
      properties was also performed using conductivity measurements on a maltose-water
      KC1 mixture. A decay in conductivity, which was almost linear with log time, was
      observed. The structural relaxation was modelled using the Tool-Narayanaswamy
      approach to describe the calorimetric data.

PMID- 11996837
TI  - The structure of the carbohydrate backbone of the rough type lipopolysaccharides
      from Proteus penneri strains 12, 13, 37 and 44.
AB  - The following structure of the lipid A-core backbone of the rough type
      lipopolysaccharides (LPS) from Proteus penneri strains 12, 13, 37, and 44 was
      determined using NMR and mass spectroscopy and chemical analysis of the
      oligosaccharides obtained by mild-acid hydrolysis, alkaline O,N-deacylation, O
      deacylation with hydrazine, and deamination of the LPSs:where K=H, R=PEtN,
      R(1)=alpha-Hep-(1-->2)-alpha-DDHep, and R(2)=alpha-GalN (strains 12 and 13) or
      beta-GlcNAc-(1-->4)-alpha-GlcN (strains 37 and 44). LPS from each strain
      contained several structural variants. LPS from strain 12 contained a variant
      with R(1)=alpha-DDHep, whereas LPS from strains 13, 37, and 44 contained
      structures with K=amide of beta-GalA with putrescine or spermidine. The phosphate
      group at O-1 of the alpha-GlcN residue in the lipid part was partially
      substituted with Ara4N.

PMID- 11996838
TI  - NMR diffusion as a novel tool for measuring the association constant between
      cyclodextrin and guest molecules.
AB  - In this paper we introduce the use of diffusion measurements by nuclear magnetic
      resonance (NMR) spectroscopy for determining association constants of weak and
      very weak interactions between cyclodextrin and guest molecules, as long as both
      the free and complexed guest molecules are soluble to an extent that allows good
      sensitivity in the NMR experiment. The experimental setup and data analysis is
      discussed for three different guest molecules: L-phenylalanine, L-leucine and L
      valine, representing different strengths of interaction. The underlying
      assumptions are discussed and the scope of the method (range of K(a) values,
      requirements to the guest molecule) are discussed. The method's main advantage is
      its general applicability independent of chromogenic or electrochemical
      properties of the guest molecule. Whereas calorimetric methods that exhibit a
      similar generality, are applicable mainly to strong interactions, NMR diffusion
      measurements are applicable to weaker interactions down to the theoretical limit
      of 1 M(-1), the upper limit for K(a) values to be determined by it is
      approximately 200. A further advantage of the method is the low amount of sample
      needed. The method is in principle applicable to any case of molecular
      recognition between a host and guest molecule leading to weak interactions.

PMID- 11996839
TI  - The crystal structure of the alpha-cellobiose.2 NaI.2 H(2)O complex in the
      context of related structures and conformational analysis.
AB  - The crystal structure of beta-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranose
      (alpha-cellobiose) in a complex with water and NaI was determined with Mo
      K(alpha) radiation at 150 K to R=0.027. The space group is P2(1) and unit cell
      dimensions are a=9.0188, b=12.2536, c=10.9016 A, beta=97.162 degrees. There are
      no direct hydrogen bonds among cellobiose molecules, and the usual intramolecular
      hydrogen bond between O-3 and O-5' is replaced by a bridge involving Na+, O-3, O
      5', and O-6'. Both Na+ have sixfold coordination. One I(-) accepts six donor
      hydroxyl groups and three C-H***I(-) hydrogen bonds. The other accepts three
      hydroxyls, one Na+, and five C-H***I(-) hydrogen bonds. Linkage torsion angles
      phi(O-5) and psi(C-5) are -73.6 and -105.3 degrees, respectively (phi(H)=47.1
      degrees and psi(H)=14.6 degrees ), probably induced by the Na+ bridge. This
      conformation is in a separate cluster in phi,psi space from most similar
      linkages. Both C-6-O-H and C-6'-O-H are gg, while the C-6'-O-H groups from
      molecules not in the cluster have gt conformations. Hybrid molecular
      mechanics/quantum mechanics calculations show <1.2 kcal/mol strain for any of the
      small-molecule structures. Extrapolation of the NaI cellobiose geometry to a
      cellulose molecule gives a left-handed helix with 2.9 residues per turn. The
      energy map and small-molecule crystal structures imply that cellulose helices
      having 2.5 and 3.0 residues per turn are left-handed.

PMID- 11996840
TI  - Synthesis and intramolecular transesterifications of pivaloylated methyl alpha-D
      galactopyranosides.
AB  - Selective pivaloylations of methyl alpha-D-galactopyranoside have been studied
      under various reaction conditions. Partially pivaloylated products were submitted
      to additional acetylations. The structures were established by 1H and 13C NMR
      spectroscopies. Both, 2,6- and 3,6-dipivalates underwent intramolecular
      cyclization in neutral conditions (phosphate buffered saline, pH 7.2) to give a
      stable 2,3-orthoacid with a parallel 6-->4 migration of the pivaloyl group.

PMID- 11996841
TI  - Structure of the O-specific polysaccharide of the lipopolysaccharide of
      Azospirillum brasilense Sp245.
AB  - An O-specific polysaccharide was isolated from the lipopolysaccharide of a plant
      growth-promoting bacterium Azospirillum brasilense Sp245 and studied by sugar
      analyses along with one- and two-dimensional 1H and 13C NMR spectroscopy,
      including NOESY. The polysaccharide was found to be a new rhamnan with a
      pentasaccharide repeating unit having the following structure:-->2)-beta-D-Rhap
      (1-->3)-alpha-D-Rhap-(1-->3)-alpha-D-Rhap-(1-->2)-alpha-D-Rhap-(1-->2)-alpha-D
      Rhap-(1-->

PMID- 11996843
TI  - Improving the detection of evoked responses to periodic stimulation by using
      multiple coherence--application to EEG during photic stimulation.
AB  - The coherence between the stimulation signal and the electroencephalogram (EEG)
      has been used in the detection of evoked responses. However the detector's
      performance depends on both the signal-to-noise ratio (SNR) of the responses and
      the number of data segments (M) used in coherence estimation. In this work, a
      technique for detecting evoked responses was developed based on the extension to
      the multivariate case of this coherence. Thus, instead of using the EEG collected
      at a unique region, the estimation is proposed using two EEG derivations. As for
      the univariate case, this multiple coherence is independent of the stimulation
      signal. In addition, considering equal SNR in both signals, the detection rate
      with this multiple coherence is always greater than that one using only one
      signal. This was verified in Monte Carlo simulations, which also showed that a
      superior performance is still expected in practical situations, when a smaller
      SNR is found in the second signal. The results with EEG from 12 normal subjects
      during photic stimulation confirm this better performance. Since the proposed
      technique allows a higher detection rate without the need of increasing M, it
      permits evoked responses to be detected faster, which is very useful during
      monitored surgeries.

PMID- 11996844
TI  - Simulation of mechanical responses of fingertip to dynamic loading.
AB  - Extended exposure to mechanical vibration has been related to many vascular,
      sensorineural and musculoskeletal disorders of the hand-arm system, frequently
      termed 'hand-arm vibration syndrome' (HAVS). A two-dimensional, nonlinear finite
      element model of a fingertip is developed to study the stress and strain fields
      of the soft tissue under dynamic loading, that may be encountered while grasping
      and operating a hand-held power tool. The model incorporates the most essential
      anatomical elements of a fingertip, such as soft tissue, bone, and nail. The
      finger is assumed to be in contact with a steel plate, simulating the interaction
      between the fingertip and a vibrating machine tool or handle. The soft tissue is
      assumed to be nonlinearly visco-elastic, while the nail, bone, and steel plate
      are considered to be linearly elastic. In order to study the time-dependent
      deformation behavior of the fingertip, the numerical simulations were performed
      under ramp-like loading with different ramping periods and sinusoidal vibrations
      of the contacting plate at three different frequencies (1, 10, and 31.5 Hz).
      Owing to relatively large deformations of the soft tissue under specified static
      and dynamic loading, Lagrangian large deformation theory was applied in the
      present analysis. The effects of the loading rate and the frequency of the
      sinusoidal vibration on the time-dependent strain/stress distributions in the
      different depth within the soft tissue of the fingertip are investigated
      numerically. Our simulations suggest that the soft tissue of the fingertip
      experiences high local stress and strain under dynamic loading and the fingertip
      may separate from the vibrating contact surface due to the viscous deformation
      behaviour of the soft tissue. For a given deformation, the high frequency loading
      produces a higher stress in the tissues compared to that obtained at a low
      frequency loading. The present model may serve as a useful tool to study the
      mechanism of tissue degeneration under vibratory loading encountered during
      operation of hand-held power tools.

PMID- 11996845
TI  - Numerical study on three-region thawing problem during cryosurgical re-warming.
AB  - Knowledge of the temperature transients of biological bodies during cryosurgical
      re-warming is critical for the survival of healthy tissues. To better understand
      the mechanisms thus involved, a one-dimensional numerical algorithm based on
      finite difference method was applied to simultaneously solve the thawing
      processes occurring in three regions with one thawing, another blood-perfused and
      the third frozen one sandwiched between them. Two typical surface heatings with
      heating plate or convective warm water and a spatial heating using microwave were
      particularly adopted to investigate the advancement of the two phase-change
      interfaces and the transient temperature field over the tissue. Differences among
      these results were compared and their implementation for the cryosurgical re
      warming were discussed. Parametric studies were performed to explore influences
      of the blood perfusion, the microwave heating power, the surface heat convection
      coefficient, and the surface heating temperature to the thermal history of the
      biological bodies. Taking account of several typical blood re-flow patterns most
      probably occurred in the originally frozen and then thawed tissues after the two
      phase change interfaces meet together, four heat transfer equations were proposed
      to characterize the re-warming behavior of the biological body. Effect of the non
      ideal solution property of the living tissues to the transient temperature field
      during cryo-surgical re-warming was also tested through introducing a simple
      however intuitive way.

PMID- 11996846
TI  - Arterial compliance is a main variable determining the effectiveness of intra
      aortic balloon counterpulsation: quantitative data from an in vitro study.
AB  - Quantitative data concerning the effect of arterial compliance (AC) on the
      effectiveness of intra-aortic balloon counterpulsation (IABC) are lacking. The
      main objective of this study was to investigate the relationship between AC and
      IABC performance. For this purpose we constructed a Windkessel, lumped-element,
      hydraulic model of the systemic circulation. The model consisted of a left
      ventricular assist device (LVAD), a compliance chamber, a peripheral resistor and
      two open reservoirs. Two Datascope Driving systems were used to operate the LVAD
      and intra-aortic balloon. We studied the effect of arterial compliance on the
      effectiveness of IABC at different levels of mean pressure (55, 75 and 95 mmHg)
      and heart rates (80, 100, 120 bpm). Three indices were used to evaluate IABC
      performance: the reduction of systolic and end-diastolic "arterial" pressure and
      the augmentation of diastolic pressure, induced by the IABC. A 22% decrease in AC
      (1.8-1.4 ml/mmHg) lead to a 30-40% increase in the indices of IABC performance,
      independently from pressure. In conclusion, arterial compliance significantly
      affects IABC efficacy and it could be considered as a further clinical criterion
      to decide IABC application.

PMID- 11996847
TI  - A transmission line model of the human foetal circulatory system.
AB  - A transmission line model of the human foetal circulatory system is presented.
      The model has been developed in the frequency domain with the cardiac input
      modeled as a flow rather than as a pressure pulse and is structured upon
      electrical transmission line analogies. The model is formed by cascading
      solutions to the two-dimensional Navier-Stokes equations for both oscillatory and
      steady, laminar viscous fluid flow in isotropic visco-elastic tubes with thick
      walls, which are constrained by surrounding tissues. Simulations allow for
      representation of both forward and retrograde travelling flow and pressure waves
      in all of the main foetal arterial vessels. The solution is verified by a
      comparison of model generated Doppler indices in the thoracic aorta, abdominal
      aorta, iliac artery and both ends of the umbilical arteries with previously
      published indices obtained by clinical measurements in these arteries. For
      simulations of blood flow in a healthy foetus, the model generated Pulsatility
      and Resistance indices were on average within 8% of the corresponding clinical
      measurements. The model results also demonstrates that placental resistance must
      increase by a factor of three, corresponding to a 60% decrease in flow to the
      placenta, before umbilical arterial absent end diastolic flow is observed.
      Differences between indices obtained from simulations at opposite ends of the
      umbilical arteries increase with increasing placental resistance.

PMID- 11996848
TI  - Estimation of out-of-plane vertebra rotations on radiographic projections using
      CT data: a simulation study.
AB  - This study extends previous research concerning in vivo intervertebral motion by
      means of single-plane fluoroscopy in an attempt to overcome 2D analysis
      limitations. Knowledge of out-of-plane vertebra rotations will extend the results
      provided by planar kinematic studies, which is particularly important for lateral
      bending investigation where axial rotation accompanies side bending, but is also
      valuable in sagittal analysis (e.g. indicating an absence of coupled axial
      rotation). Combining a fluoroscopic projection of a vertebra with volumetric
      information provided by CT data, vertebra 3D position can be estimated. Out-of
      plane vertebral rotations are estimated by comparing Digitally Reconstructed
      Radiographs (DRRs) in different orientations with a reference fluoroscopic
      projection, maximising the image cross-correlation index. DRRs have been computed
      from CT-data using a ray-casting algorithm. In this work a feasibility study of
      the method was performed by means of a computer simulation. To this end the CT
      volume (vertebra L4, segmented) provided by the Visible Human Project was
      utilised and reference fluoroscopic projections were simulated in different
      orientations adding various levels of noise. Accuracy and precision of the
      proposed method was determined. Error analysis reveals that an accuracy of less
      than 1 degree can be achieved in computation of out-of-plane vertebral angles.

PMID- 11996849
TI  - Effect of hemolysis on oxygen and hematocrit measurements by near infrared
      reflectance spectroscopy.
AB  - A short review of the principles of near infrared reflectance spectroscopy (NIRS)
      in whole blood is followed by a discussion on the influence of hemolysis. The
      increase of free plasmahemoglobin (PHb) has a strong influence on the continuous
      measurement of hematocrit and oxygen saturation (O(2)S) by NIRS. In view of the
      relative stability of hematocrit values in vivo this effect may be used to detect
      a change of the hemolysis rate induced by blood pumps in case of malfunction. The
      aim of this study is, therefore, the assessment of the hemolysis rate within an
      in vitro mock loop comprising a rotary blood pump by means of NIRS at constant
      hematocrit levels compared to the photometric reference method. Reflected light
      is measured by an integrated optical sensor working at three wavelengths (660 nm,
      730 nm, and 830 nm). The experimental results demonstrate that the increase of
      free hemoglobin in plasma due to mechanical pumping leads to a decrease of
      detected reflected light at all three wavelengths. Influencing parameters such as
      adhering proteins on the sensor surface and the blood flow rate are briefly
      discussed. Finally, the possibility of using NIRS sensors for detecting
      malfunctions of blood pumps in vitro and in vivo is discussed, together with the
      option of using these sensors for supervision of long-term implantable pumps.

PMID- 11996850
TI  - Protective role of cyclooxygenase (COX) inhibitors in burn-induced intestinal and
      liver damage.
AB  - The aim of this study was to investigate the role of cyclooxygenase (COX)
      inhibition in intestinal motility and in the extent of tissue injury of the small
      intestine and liver with the use of various COX inhibitors. Wistar albino rats
      were exposed to 90 degrees C water bath for 10s. The intestinal transit index
      decreased compared to control group and treatment with nimesulide (NIM; 10mg/kg,
      subcutaneously) or piroxicam (Pir; 5mg/kg, orogastrically) reversed this effect
      significantly. The intestinal and liver glutathione levels showed a significant
      decrease in the burn group compared to sham (P<0.001 and P<0.05, respectively).
      Decrease in intestinal glutathione level was reversed by NIM or Pir treatment
      (P<0.01 and P<0.01, respectively), whereas all drugs tested were effective in
      reversing low liver glutathione level. The MPO activity in intestinal segments
      were significantly high in burned animals compared to sham. All test drugs
      reversed this effect but ketorolac (Ket; 3mg/kg, orogastrically) was the most
      effective one. The liver samples characterized by sinusoidal dilatation and
      pericentral atrophy in burn group were protected by treatment with Ket or Pir
      (P<0.05). Plasma ALT and AST activities were markedly high in this burn group
      compared to sham (P<0.0001 and P<0.001, respectively). None of the agents
      reversed these high enzyme activities. These data suggest that not only COX-2 but
      also COX-1 inhibition is required for protection against inflammatory changes in
      liver and small intestine following burn injury.

PMID- 11996851
TI  - Oxidative stress and metallothionein expression in the liver of rats with severe
      thermal injury.
AB  - The aim of this work was to study oxidative stress and the compensating
      mechanisms implicated in severe thermal injury using the burned rat model.
      Results showed that after thermal injury glutathione (GSH) level was decreased,
      oxidized glutathione (GSSG) and the ratio of GSSG/GSH increased both at 24 and 48
      h in the liver. The activities of GSH-reductase (GSH-Rx) in the liver and GSH
      peroxidase (GSH-Px) both in the liver and erythrocytes increased at 24 h and then
      decreased at 48 h. The level of alpha-tocopherol in plasma was reduced at 24 h.
      Lipid peroxide levels increased both at 24 and 48 h in the liver. The serum zinc
      level decreased, reaching a minimum at 12h, whereas liver zinc level was elevated
      and reached the maximum at 12 h. After severe thermal injury enhancement of
      metallothionein (MT) expression has been discovered for the first time. MT
      content in the liver increased both at 24 and 48 h. Expression of MT-I mRNA was
      activated at 3 h and reached the top at 24 h postburn. The conclusion is that
      severe thermal injury gives rise to oxidative stress and dramatic enhancement of
      MT expression could be one of the important compensative mechanisms of natural
      defense system postburn.

PMID- 11996852
TI  - Thermal injury induces expression of CD14 in human skin.
AB  - BACKGROUND: Skin is equipped with an array of immune mediators aimed at fighting
      invading microbes. CD14 has been shown to play a key role in modulating the
      activation of cells by LPS. Since LPS levels within burn wounds are often found
      to be elevated, we sought to examine the expression of CD14 within human skin
      following thermal injury. METHODS: Patients who sustained partial thickness
      burns, were recruited into the study (n=57). Total RNA was isolated from both
      burn and normal (control) skin. Northern blot analysis and TaqMan RT-PCR were
      used to determine skin CD14 mRNA levels. Immunohistochemistry was used to
      localize CD14 expression in burned and normal skin. RESULTS: Quantitative PCR
      showed significantly increased CD14 expression levels in the immediate post-burn
      period (P<0.05 burn versus non-burn). Immunohistochemistry revealed more
      pronounced CD14 staining 24 h after the injury, reaching normal levels
      approximately 5-7 days post-burn. CONCLUSION: CD14 expression peaks within the
      first week post-burn before declining, reaching normal levels after 14 days. This
      loss of supranormal CD14 expression locally within the wound may contribute to a
      weakened host defense response 5-6 days after injury, when patients become
      especially vulnerable to infection.

PMID- 11996853
TI  - A retrospective analysis of 1083 Turkish patients with serious burns.
AB  - A total of 1083 burn cases hospitalised at a burn center between August 1988 and
      the end of 1997 were studied retrospectively to determine the factors and
      demographic features associated with burn injury in Turkey. The means for patient
      age and percent total body surface area (TBSA) burned were 18.1 years and 31.2%,
      respectively (medians were 14.0 years and 25.0%, respectively). Burn injuries
      were more common in winter and spring, and most occurred in the home. The
      majority of patients were city dwellers, and had been referred from public
      hospitals. There was a predominance of male patients (71.9%) in the study
      population, but the proportions of children and adults were equal. Almost half of
      the males and the majority of the females were children/students. The vast
      majority of female adults were housewives, and most of the men were employed
      outside the home. More than half of the patients suffered second-degree burns,
      and the others all had deeper burn injuries. The most frequent cause of burn in
      the study population was flame. Children mainly suffered from scalding, and
      adults from flame and electrical burns. There were no differences between the
      sexes regarding depth of burn; whereas percentage total burned surface area was
      higher in females. Children had a lower mean TBSA and lower rate of third-degree
      burns. Mortality rate of the study population was 33.5%. The study results
      identified various risk factors and the groups at high risk for serious burns and
      indicated some ways that prevention programmes can be improved.

PMID- 11996854
TI  - A retrospective analysis of 1083 Turkish patients with serious burns. Part 2:
      burn care, survival and mortality.
AB  - Epidemiological investigations of burn patient series help practitioners to
      identify factors that affect patient survival. Our aim was to contribute to the
      body of knowledge in this area by determining how survival related to certain
      variables in burn cases. The records of 1083 burn patients who were hospitalised
      between August 1988 and the end of 1997 were retrospectively reviewed. Of this
      total, 363 (33.5%) died of burn complications, namely, multi-organ injury due to
      sepsis (47.1% of deaths), renal failure (44.6%), respiratory injury (5.8%) and
      gastrointestinal bleeding (2.5%). Mortality was higher in children/students,
      females, retired persons. Extent and depth of burn were important predictors of
      patient survival. Flame not only was the commonest burn cause but also carried
      the highest mortality risk. Most of the 1083 patients were referred to our
      hospital within 3 days of the injury. Deaths commonly occurred within 7 days. The
      mortality rate for patients who received medical therapy only was higher than
      that in the group that underwent both medical and surgical treatment (48.4 versus
      10.0%, respectively). The study results highlighted various factors that are
      related to patient survival. These should be considered in the provision of
      optimal burn care. Training and experience are important elements in burn care
      and educational meetings should be held regularly for the staff of the burn unit.

PMID- 11996855
TI  - Burns due to gunpowder explosions in fireworks factory: a 13-year retrospective
      study.
AB  - The aim of this study was to evaluate the epidemiology of burns due to gunpowder
      explosions in fireworks factories. Three hundred and fifty-one patients having
      burns caused by gunpowder explosions in a fireworks factory were admitted to our
      center from 1 January 1987 to 31 December 1999 and the clinical notes of 339
      patients were available for review. Data on age, sex, size, depth and sites of
      burn, incidence by month, inhalation injury, associated injuries, number of
      operations, length of hospital stay, morbidity, mortality, and causes of
      explosions were recorded. The majority of the patients were male, with a mean age
      of 36.7 years. The mean total burn surface area was 40.9%, mostly deep burns. The
      commonest areas of the body to be injured were the head and neck. One hundred and
      eighty-five patients (55%) were injured in December, November, and January. Sixty
      five patients (19%) had an inhalation injury, 35 having tracheotomies and
      mechanical ventilation. Thirty-five patients (10%) had associated injuries, the
      commonest being the fracture of limbs (25 patients). Two hundred and thirty-two
      patients (68%) required operations while the number of operations including
      debridement and grafting, or tracheotomy, per patient were 2.7. The mean time in
      hospital of the survivors was 32 days with a range of 1-94 days. Acute
      respiratory distress syndrome (ARDS) and sepsis were the commonest complications
      during the early post-burn period (7 days or less) and the later period (>7
      days), respectively. Forty-four patients died in this series giving a mortality
      rate of 13%. The commonest cause of death was sepsis (27 patients), followed by
      multiple organ dysfunction syndrome (MODS) (11 patients). Most accidents (71%)
      were caused by too much gunpowder put in at one time and accidents resulting from
      carelessness while making fireworks. Prevention measures are also discussed.

PMID- 11996856
TI  - Kitchen accidents vis-a-vis dowry deaths.

PMID- 11996857
TI  - Allogeneic skin substitutes applied to burns patients.
AB  - Early re-surfacing of burn wounds remains the ideal but is limited by the
      availability of skin graft donor sites. Cultured grafts overcome these problems
      and autologous keratinocytes can be grown in culture and placed on a dermal
      substitute, but this results in delay and requires two operations. We developed
      an organotypic skin substitute, which achieves cover in one procedure, and have
      previously found allogeneic cell survival up to 2.5 years after grafting onto
      clean elective wounds (tattoo removal). Here, we report a short series using the
      same model applied to burns patients with less than 20% total body surface area
      affected. The skin substitutes consisted of allogeneic dermal fibroblasts
      embedded in a collagen gel overlain with allogeneic epidermal keratinocytes, and
      were grafted to patients with tangentially excised burns. A side-by-side
      comparison with meshed split-thickness autografts was performed. No grafts became
      infected. The allogeneic skin substitute showed little effective take at 1 week,
      and by 2 weeks only small islands of keratinocytes survived. These sites were
      subsequently covered with meshed split-thickness autograft, which took well. It
      is concluded that further development of this model is needed to overcome the
      hostile wound bed seen in burns patients.

PMID- 11996858
TI  - Effects of arginine supplementation on antioxidant enzyme activity and macrophage
      response in burned mice.
AB  - This study investigated the effect of arginine (Arg) supplementation on
      antioxidant enzyme activities and macrophage response in burned mice. Experiment
      1: 60 male BALB/c mice were assigned to two groups. One group was fed a control
      diet with casein as the protein source, the other group was supplemented with 2%
      Arg in addition to casein. The two groups were isonitrogenous. After 4 weeks, all
      mice received a 30% body surface area burn injury. The antioxidant enzyme
      activities and lipid peroxides in the tissues were analyzed. Experiment 2: 20
      mice were divided into two groups and burn injury was induced after feeding for 4
      weeks as described in experiment 1. Twenty-four hours after the burn, tumor
      necrosis factor-alpha (TNF-alpha) secreted by cultured peritoneal macrophages was
      measured. The results show that antioxidant enzyme activities and lipid peroxides
      in tissues tended to be lower in the Arg group than in the control group after
      the burn. Production of TNF-alpha by peritoneal macrophages after stimulation
      with lipopolysacchride (LPS) was significantly elevated in the Arg group, whereas
      no response was observed in the control group. These results suggest that dietary
      Arg supplementation attenuates the oxidative stress induced by burn injury, and a
      better macrophage response was observed when Arg was administered.

PMID- 11996859
TI  - The rate of re-epithelialization across meshed skin grafts is increased with
      exposure to silver.
AB  - The objective in this study was to determine whether exposure to pure silver
      increases the rate of re-epithelialization across a partial thickness wound. A
      meshed skin graft, placed on an excised burn wound was used as a healing model.
      METHODS: The rate of meshed skin graft epithelial closure on an exposed burn
      using a moist healing environment was shown. A moistened silver delivery system
      (Acticoat) was compared with a standard xeroform and eight ply gauze dressing
      continually moistened with a 0.01% neomycin and polymyxin solution (NP). Twenty
      burn patients with deep burns of over 15% of TBS were excised and grafted with
      2:1 meshed grafts. One graft area was treated with the antibiotic solution and
      another with the silver delivery. The meshed graft was performed within 3 days of
      injury. RESULTS: No infections were noted and quantitative swab cultures gave
      less than 10(2) bacteria in all cases at wound closure. At day 7, re
      epithelialization was complete with silver and 55% closed with NP solution. Wound
      closure was complete in the NP solution group at day 10. Silver increased re
      epithelialization rate by over 40%, a significant increase. Graft take was over
      95% in both groups. CONCLUSION: Silver released in a moist wound surface
      environment significantly increases the rate of re-epithelialization compared to
      a standard antibiotic solution.

PMID- 11996860
TI  - Use of skin staples to fix film dressings on scalp donor wounds in patients with
      burns.
AB  - Split-thickness skin grafts (STSGs) from the scalp have been used in large burns.
      The donor site wounds are usually covered using occlusive dressings, such as film
      dressings because they contribute to reduce donor site pain and infection under
      exudative crust and to enhance re-epithelialization. However, it is not always
      easy to fix such film dressings to the scalp because of the presence of hair. In
      this paper, we report the use of skin staplers to fix the film dressings. Eight
      donor sites in four patients were dressed in this way. The patients had 50-78% of
      the body burned, all of them survived. The mean healing time for the donor sites
      was 6.8 days. Three patients had their scalps re-harvested several times (range
      two to three times). There were no infections nor secondary skin ulcers at the
      donor sites. The technique of this dressing is very simple and speedy, thus we
      recommend the use of skin staplers to fix the film dressing to scalp donor wounds
      in patients with burns.

PMID- 11996861
TI  - Hemodynamic instability secondary to adrenal insufficiency in a major burn
      patient.
AB  - A 39-year-old man presented with 80% body surface area burned following a thermal
      accident. The patient showed hemodynamic instability and low response to
      intravenous fluids or vasopressors for 20 days in the intensive care unit (ICU).
      The adrenocorticotropic hormone (ACTH) test was consistent with adrenal
      insufficiency. After a 3-day steroid treatment, the patient's blood pressure was
      normal without the administration of any vasopressor.

PMID- 11996862
TI  - Free vascularized nail grafts for onychogryphosis of bilateral thumbnails after
      burn injury.
AB  - Free vascularized grafts of the toenails were used to repair bilateral
      onychogryphosis occurring after burn injury.

PMID- 11996863
TI  - Cataract formation after a major burn due to explosion: a case report.
AB  - Cataract is a very rare complication of burn injuries in which the eye is not
      directly marked. A unilateral cataract presented some 85 days after a burn injury
      to a 21-year-old soldier. The cataract was treated surgically with excellent
      return of vision.

PMID- 11996864
TI  - Porcin xenograft dressing for facial burns: beware of the mesh imprint.

PMID- 11996865
TI  - Major thermal burn due to intraoperative heating blanket malfunction.

PMID- 11996866
TI  - Tissue engineering--a shifting paradigm.

PMID- 11996867
TI  - Vasoactive intestinal peptide and nitric oxide (NO) in the acute phase following
      burns and trauma.

PMID- 11996869
TI  - Nursing approaches to reducing psychological distress in men and women recovering
      from myocardial infarction.
AB  - This paper examines the types of nursing approaches associated with reductions in
      psychological distress in post-myocardial infarction patients (n=275 men; 156
      women) who took part in a home-based psychosocial nursing Intervention program
      (Montreal Heart Attack Readjustment Trial). We found that three types of
      emotionally supportive approaches including reassurance/encouragement, listening
      and the provision of advice varied in their links to reduction in distress
      depending on patients' types of concerns. There were also gender differences in
      the way directive and collaborative intervention approaches were related to
      changes in distress.

PMID- 11996870
TI  - Lived experiences of immigrant nurses in New South Wales, Australia: searching
      for meaning.
AB  - Recognising the potential value of immigrant nurses in multicultural Australia,
      this study sought to understand immigrant nurses' experiences in order to throw
      some light on their under representation in the nursing workforce. Using a
      Heideggerian phenomenological approach the purpose of this study was to explore,
      describe and analyse the lived experiences of five immigrant nurses, four from
      non-English-speaking backgrounds, practising in New South Wales, Australia.
      Through naturalistic open-ended interviews, the everyday experiences of immigrant
      nurses were described and hermeneutically analysed. The lived experiences, and
      the meaning of such experiences which emerged from analysis included:
      professional negation, experienced in lack of support; otherness, experienced in
      cultural separateness; silencing, experienced in language and communication
      difficulties and a number of other related experiences and feelings. The study
      highlights the continuing existence of a social and cultural distance between
      nurses of the dominant culture and nurses from culturally and linguistically
      diverse backgrounds.

PMID- 11996871
TI  - 'Entering a New World': empathic awareness as the key to positive family/staff
      relationships in care homes.
AB  - Despite an almost universal policy of community care, placing a relative in a
      care home will be an increasingly common event as population ageing continues.
      Studies suggest that most families wish to remain involved in care following
      placement but that they often experience difficulties in establishing
      relationships with staff. This paper reports on the fifth phase of a Swedish
      study exploring the experience of placement from a temporal perspective and
      including the views of all the key actors (relatives, staff in the community,
      staff in care homes). The focus here is placed on the perceptions of care home
      staff and their perceived role in relation to spouses who have recently placed a
      partner. The study adopted a grounded theory approach and data were collected
      from in-depth interviews with 16 staff members of varying grades and positions.
      Analysis of the data suggested 3 levels of awareness amongst staff: empathic
      awareness, guarded awareness and limited awareness. The characteristics of
      empathic awareness are outlined and its implications briefly considered.

PMID- 11996872
TI  - Associations between student learning outcomes from their clinical placement and
      their perceptions of the social climate of the clinical learning environment.
AB  - The aim of this study was to investigate the associations between student
      learning outcomes from their clinical placement and their perceptions of the
      social climate of the clinical learning environment. The Clinical Learning
      Environment Inventory (CLEI) was used to collect data. The final sample group
      consisted of 108 second-year nursing students undertaking clinical placement in
      14 metropolitan hospitals in South Australia. Findings from the study suggested
      that students' perceptions of the outcomes of their clinical placement are
      strongly associated with all five scales of the CLEI namely; Individualisation,
      Innovation, Involvement, Personalisation and Task Orientation. It is interesting
      to note that student who perceived the outcomes of their clinical placement as
      greatly positive, have placed high expectations on the scale, Task Orientation.
      The study also found that there were significant differences between students'
      perceptions of the actual clinical learning environment with their preferred
      clinical learning environment. The value of this study lies in the resulting
      implication for nursing education and future research. A better understanding of
      what constitutes quality clinical education from the students' perspective would
      be valuable in providing better educational experiences.

PMID- 11996873
TI  - Primary and preferred sources for HIV/AIDS and sexual risk behavior information
      among adolescents in Swaziland, Southern Africa.
AB  - The HIV/AIDS epidemic in Sub-Saharan Africa poses a massive diffusion and
      persuasion challenge for health professionals. Individuals working with
      adolescents to prevent the spread of HIV/AIDS must gain an understanding of
      adolescent's preference in obtaining information about HIV/AIDS and sexual
      behaviors. This study describes the primary and preferred sources of information
      regarding HIV/AIDS and sexual risk behavior in relation to several socio
      demographic variables (n=941) in Swaziland, Southern Africa. Although
      print/broadcast media was the primary source for HIV/AIDS and sexual risk
      behavior information for the students, most participants preferred information
      from the healthcare workers. This study suggests a greater role for healthcare
      providers in providing HIV/AIDS and sexual risk information.

PMID- 11996874
TI  - The effect of an integrated stress management program on the psychologic and
      physiologic stress reactions of peptic ulcer in Korea.
AB  - The purpose of this study was to identify the effects of an integrated stress
      management program on symptoms of stress and ulcer healing in a sample of Koreans
      at a major medical center in Seoul, Korea. The study employed an experimental
      design with two treatment groups. One treatment group (n=23) participated in an
      integrated stress management program that consisted of seven 1h sessions over a 4
      week period. A second treatment group (n=24) was only given a tape on progressive
      muscle relaxation. Data were collected over a 4-month period on 47 subjects.
      Participants were randomly assigned to the two treatment groups. Symptoms of
      stress were measured by the symptoms of stress scale (Kogan, Self-regulation on
      Stress Reaction by Biofeedback, Korean Psychiatric Academic Society, Korea)
      translated into Korean. Stage of ulcer healing was evaluated by a physician using
      an endoscope. Physiologic stress reactions were measured by biofeedback
      equipment. The integrated stress management program treatment group reported
      significantly lower stress symptom scores than the progressive muscle relaxation
      only group (t=3.66, P<0.001). The integrated stress management group also
      demonstrated a greater improvement in ulcer healing than the progressive muscle
      relaxation group (t=1.95, P<0.05). The integrated stress management program was
      more effective in decreasing self-reported stress symptoms and resulted in a more
      significant ulcer healing than the progressive muscle relaxation treatment.

PMID- 11996875
TI  - A randomized trial on the effects of body positions on lung function with acute
      respiratory failure patients.
AB  - In a randomized controlled trial, we compared the potential benefits of position
      changes on arterial oxygen pressure in 32 patients with acute respiratory
      failure, maintained on artificial ventilators, distinguishing prominently as left
      sided, right-sided or bilateral lung disease. Our results indicate that randomly
      alternating supine, left-lateral, right-lateral and prone positions have
      influence on gas exchange and that improvement of arterial oxygen pressure is
      associated with various positions. Our results show, therefore, that nursing care
      of patients on artificial ventilators involving changes in body positions (a
      simple and noninvasive means of assistance) has important therapeutic
      consequences and warrants attention in clinical practice.

PMID- 11996876
TI  - Medical decisions for troubled breathing in nursing home residents.
AB  - This paper aims to gain insight into the medical decision-making processes
      undergone in a nursing home in response to troubled breathing. Participants were
      20 residents of a large, nonprofit nursing home, six of whom died by the time of
      data collection. The mean age was 88 yr, and 70% were female. Diagnostic tests
      and medication were the most frequently used treatments. The most important
      considerations reported were the resident's quality of life, family wishes, and
      the relative effectiveness of alternative treatment options. In 45% of the cases,
      the physicians reported family involvement. In 30% of cases, the physicians would
      have wanted less treatment if they were in the resident's condition. Troubled
      breathing emerges as an end-of-life symptom for many residents. An analysis of
      the decision-making process and its evaluation could foster improved care of
      these symptoms.

PMID- 11996877
TI  - Patients' verbal descriptions of pain and discomfort following orthopaedic
      surgery.
AB  - The concepts of pain and discomfort are poorly differentiated in the literature.
      This study of 417 post-operative orthopaedic patients examined their use of
      language to describe pain and also discomfort. Their pain descriptions were
      assessed for congruence with the widely used McGill pain questionnaire (MPQ). The
      findings confirmed that there was an overlap in the descriptions of pain and
      discomfort, but that pain tended to be described as an internal phenomenon, while
      discomfort was frequently related to environmental stimuli. The use of analogy
      was commonly used to describe pain. There was considerable use of words not
      included in the MPQ. This suggests that regional and international variations in
      vocabulary may render the MPQ unsuitable for indiscriminate use in Anglophone
      countries. Implications for improving pre-operative information provision and
      post-operative assessment of pain and discomfort are briefly presented.

PMID- 11996878
TI  - Pharmacological approaches to prion research.
AB  - The "protein-only" mechanism by which infectious agents of prion diseases such as
      Creutzfeldt-Jakob disease and bovine spongiform encephalopathy replicate remains
      undetermined. The identification of several distinct classes of prion inhibitors
      has created an opportunity to investigate the mechanism of prion formation using
      pharmacological tools. These new inhibitors include substituted tricyclic
      derivatives, tetrapyrrole compounds, cysteine protease inhibitors, branched
      polyamines, and specific antibodies. Each inhibitor class contains at least one
      active compound that inhibits prion propagation in cell culture at sub-micromolar
      concentrations and several structurally related, inactive compounds. Work with
      branched polyamines and specific antibodies has already provided insight into the
      kinetics and cell biology of endogenous prion clearance mechanisms. Other anti
      prion compounds do not appear to bind directly to the prion protein. Detailed
      investigation of the mechanism of drug action of these compounds may lead to the
      identification of novel prion propagation factors.

PMID- 11996879
TI  - Apoptosis of a human non-small cell lung cancer (NSCLC) cell line, PLA-801,
      induced by acutiaporberine, a novel bisalkaloid derived from Thalictrum
      acutifolium (Hand.-Mazz.) Boivin.
AB  - Acutiaporberine is a novel ether-linked bisalkaloid isolated from the traditional
      Chinese medicinal herb Thalictrum acutifolium (Hand.-Mazz.) Boivin (TAB). The
      present study demonstrates for the first time, by means of nuclear staining, DNA
      agarose gel electrophoresis, and flow cytometry, that acutiaporberine induces
      apoptosis in PLA-801 cells, a cultured human non-small cell lung cancer (NSCLC)
      cell line. An immunohistochemical assay and western immunoblot analysis showed
      down-regulation of the bcl-2 gene and up-regulation of the bax and c-myc genes in
      the acutiaporberine-treated cells. The observations also indicate that
      acutiaporberine induces apoptosis of PLA-801 cells in a concentration- and time
      dependent manner. These results suggest that acutiaporberine may be a potential,
      natural apoptosis-inducing agent for NSCLC.

PMID- 11996880
TI  - Regulation of microsomal and cytosolic glutathione S-transferase activities by S
      nitrosylation.
AB  - There is increasing evidence that S-nitrosylation is a mechanism for the
      regulation of protein function via the modification of critical sulfhydryl
      groups. The activity of rat liver microsomal glutathione S-transferase (GST) is
      increased after treatment with N-ethylmaleimide (NEM), a sulfhydryl alkylating
      reagent, and is also increased under conditions of oxidative stress. In the
      present study, preincubation of purified rat liver microsomal GST with S
      nitrosoglutathione (GSNO) or the nitric oxide (NO) donor, 1,1-diethyl-2-hydroxy-2
      nitrosohydrazine (DEA/NO), resulted in a 2-fold increase in enzyme activity. This
      increase in activity was reversed by dithiothreitol. The initial treatment of
      microsomal GST with either GSNO or DEA/NO was associated with an 85% loss of free
      sulfhydryl groups. After removal of the nitrosylating agents over a 6-hr period,
      approximately 50% of the enzyme was still nitrosylated, as determined by redox
      chemiluminescence. Furthermore, preincubation of either purified enzyme or
      hepatic microsomes with GSNO or DEA/NO prevented further enzyme activation by
      NEM, suggesting that NEM and the NO donors interact with a common population of
      sulfhydryl groups in the enzyme. In contrast, both NEM and NO donors partially
      inhibited the activity of cytosolic GST isoforms. The inhibitory activity of NEM
      and NO donors was much more evident when the GST pi isoform was used instead of a
      mixture of GST isoforms. These data suggest that there may be differential
      regulation of microsomal and cytosolic GST activities under conditions of
      nitrosative stress.

PMID- 11996881
TI  - Serum withdrawal leads to reduced aryl hydrocarbon receptor expression and loss
      of cytochrome P4501A inducibility in PLHC-1 cells.
AB  - Changes in the expression of the aryl hydrocarbon receptor (AHR) have been
      documented in several systems and in response to a variety of treatments. The
      significance of these findings is unclear, because the effects of such changes on
      subsequent responses to AHR ligands seldom have been measured. We tested the
      ability of changes in serum used in cell culture medium to alter expression of
      the AHR and induction of cytochrome P4501A (CYP1A) in PLHC-1 teleost hepatoma
      cells. Culture of early-passage cells in serum-free medium for 2 days led to a
      loss of CYP1A inducibility by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In
      contrast, culture in 10% delipidated calf serum increased the TCDD-induced levels
      of both CYP1A protein and enzymatic activity relative to levels in cells cultured
      in 10% complete calf serum. These effects were consistent between 8 and 24hr post
      treatment, indicating that the kinetics of induction were unaffected. In cells
      cultured in serum-free medium for 1 and 2 days there was a progressive loss of
      CYP1A inducibility. This loss of response paralleled a time-dependent decline in
      AHR protein, as measured by specific binding of [3H]TCDD. Using an operational
      model for AHR action in PLHC-1 cells, the measured reduction in AHR could be
      shown to predict the loss of CYP1A induction. Expression of AHR protein was
      unaffected by culture in 10% delipidated serum. The effects of serum-free medium
      and delipidated serum were found only in early-passage cells; inducibility of
      CYP1A and expression of AHR protein in late-passage cells were unaffected by
      serum withdrawal. Comparison of early- and late-passage cells revealed a 2-fold
      greater rate of proliferation in the latter, suggesting that a growth advantage
      is coincident with loss of the serum-dependency of AHR expression. These results
      provide a quantitative link between changes in receptor expression and a
      downstream response, establishing a foundation for future studies of receptor
      expression and sensitivity to toxic responses in vitro and in vivo.

PMID- 11996882
TI  - The alkaloid sanguinarine is effective against multidrug resistance in human
      cervical cells via bimodal cell death.
AB  - Sanguinarine, a benzophenanthrine alkaloid, is potentially antineoplastic through
      induction of cell death pathways. The development of multidrug resistance (MDR)
      is a major obstacle to the success of chemotherapeutic agents. The aim of this
      study was to investigate whether sanguinarine is effective against uterine
      cervical MDR and, if so, by which mechanism. The effects of treatment with
      sanguinarine on human papillomavirus (HPV) type 16-immortalized endocervical
      cells and their MDR counterpart cells were compared. Trypan blue exclusion assays
      and clonogenic survival assays demonstrated that MDR human cervical cells are as
      sensitive as their drug-sensitive parental cells to death induced by
      sanguinarine. Upon treatment of both types of cells with sanguinarine, two
      distinct concentration-dependent modes of cell death were observed. Treatment
      with 2.12 or 4.24 microM sanguinarine induced death in most cells that was
      characterized as apoptosis using the criteria of cell surface blebbing, as
      determined by light and scanning electron microscopy, and proteolytic activation
      of caspase-3 and cleavage of the caspase-3 substrate poly(ADP-ribose) polymerase
      (PARP), as detected by Western blot analysis. However, 8.48 and 16.96 microM
      sanguinarine caused a second mode of cell death, oncosis, distinguished by cell
      surface blistering, and neither caspase-3 activation nor PARP cleavage. This
      study provides the first evidence that sanguinarine is effective against MDR in
      cervical cells via bimodal cell death, which displays alternative mechanisms
      involving different morphologies and caspase-3 activation status.

PMID- 11996883
TI  - Increase of the resistance of human cervical carcinoma cells to cisplatin by
      inhibition of the MEK to ERK signaling pathway partly via enhancement of
      anticancer drug-induced NF kappa B activation.
AB  - In this study, we showed that suppression of the MEK-ERK transduction pathway by
      a selective inhibitor, 2'-amino-3'-methoxyflavone (PD98059), increased drug
      resistance of SiHa cells to cisplatin, but not to another common anticancer drug,
      doxorubicin. The downstream mechanism of this discrepant cellular response was
      investigated. Both cisplatin and doxorubicin activated nuclear ERK2 and nuclear
      transcription factor kappa B (NF kappa B) of SiHa cells. However, suppression of
      the MEK-ERK2 pathway by PD98059 resulted in a further enhancement of cisplatin
      induced NF kappa B activation, while no further regulation of NF kappa B was
      noted in doxorubicin-treated cells. The activation of NF kappa B by cisplatin or
      doxorubicin was not due to the degradation of cytoplasmic I kappa B alpha, as
      demonstrated by western blotting. Transfection of a dominant negative I kappa B
      alpha resulted in a markedly diminished PD98059-induced cisplatin resistance in
      SiHa cells. Our results suggest that the MEK-ERK signaling pathway plays a role
      in the chemosensitivity of SiHa cells, and suppression of this pathway increases
      cisplatin resistance partly via an increase of NF kappa B activation. The
      mechanism responsible for the discrepant effect of PD98059 on NF kappa B
      activation and hence the chemosensitivity of SiHa cells towards cisplatin and
      doxorubicin remains to be investigated.

PMID- 11996884
TI  - Interaction of mammalian O(6)-alkylguanine-DNA alkyltransferases with O(6)
      benzylguanine.
AB  - Human O(6)-alkylguanine-DNA alkyltransferase (hAGT) activity is a major factor in
      providing resistance to cancer chemotherapeutic alkylating agents. Inactivation
      of hAGT by O(6)-benzylguanine (BG) is a promising strategy for overcoming this
      resistance. Previous studies, which have focused on the region encompassed by
      residues Pro138 to Gly173, have identified more than 100 individual mutations
      located at 23 discrete sites at which alterations can render AGT less sensitive
      to BG. We have now extended the examination of possible sites in hAGT at which
      alterations might lead to BG resistance to include the residues from Val130 to
      Asn137, which also make up part of the binding pocket into which BG is postulated
      to fit. A further 21 mutations located at positions Gly132, Met134, Arg135, and
      Gly136 were found to lower sensitivity to BG. Mutants R135L, R135Y, and G136P
      were the most strikingly resistant, with a 50-fold increase in the amount of BG
      needed to obtain 50% inactivation. These results therefore increase the number of
      sites at which BG resistance can occur in response to a single amino acid change
      to 27. Although mammalian AGTs are very similar in amino acid sequence, mouse AGT
      (mAGT) is significantly less sensitive to BG than rat AGT (rAGT) or hAGT.
      Construction of chimeric proteins in which portions came from the rAGT and the
      mAGT indicated that the difference in inactivation resided solely in the amino
      acids located in the sequence from residues 150 to 188. Individual mutations of
      the three residues where rAGT and mAGT differ in this region showed that the
      principal reason for the reduced ability of the mAGT to react with BG was the
      presence of a histidine residue at position 161, which is occupied by asparagine
      in rAGT and hAGT. These experiments indicate that many minor changes in amino
      acids forming all parts of the nucleoside binding pocket of AGT can alter its
      ability to react with BG and that the possibility that polymorphisms or variants
      may occur reducing the effectiveness of combination therapy with BG and
      alkylating agents must be considered.

PMID- 11996885
TI  - Induction of apoptosis in HL-60 leukemia and B16 melanoma cells by the acronycine
      derivative S23906-1.
AB  - The benzoacronycine derivative S23906-1 is a highly potent antitumor agent with a
      broad spectrum of activity against different human solid tumor xenografts. The
      marked cytotoxic potential of this drug may be the result of its interaction with
      DNA but the precise mechanism of action remains unclear at present. We have
      investigated the induction of apoptosis in human promyelocytic leukemia HL-60 and
      murine melanoma B16 cells treated with S23906-1. With both cell lines, the drug
      induces cell cycle perturbations (G2/M arrest) and triggers apoptosis as revealed
      by the externalization of Annexin V-targeted PS residues at the periphery of the
      cells. But the biochemical pathways leading to apoptosis are different for the
      two cancer cell lines. In HL-60 cells, the drug induces significant variations of
      the Delta Psi(mt), measured by flow cytometry using the fluorochromes JC-1 and cm
      X-ros. Activation of caspase-3 and chromatin condensation in HL-60 cells exposed
      to submicromolar concentrations of S23906-1 for 24hr were also clearly seen by
      flow cytometry and confocal microscopy experiments. In contrast, the extent of
      apoptosis induced by S23906-1 was found to be much more limited in B16 cells. No
      significant variations of Delta Psi(mt) and no cleavage of the fluorescent
      caspase-3 substrate GDEVDGI (PhiPhiLux-G(1)D(2) probe) could be detected by
      cytometry in B16 cells exposed to S23906-1. In addition, we characterized the
      mitochondrial production of reactive oxygen species (ROS) using the probe
      dihydroethidine (HE) and the variations of the mitochondrial mass using the
      cardiolipin-interacting probe nonyl acridine orange (NAO). S23906-1 stimulates
      the production of ROS in both cell lines but the number of mitochondria seems to
      increase only in drug-treated B16 cells. Collectively these findings identify
      S23906-1 as a potent inducer of cell apoptosis in the leukemia cells and to a
      lower extent in the melanoma cells. The results help to understand the downstream
      cytotoxic actions of this new anticancer agent which is currently undergoing
      preclinical development.

PMID- 11996886
TI  - Physiological factors affecting the expression of FMO1 and FMO3 in the rat liver
      and kidney.
AB  - FMO1 and FMO3, the main FMOs described in the rat, are highly expressed in the
      liver and the kidney. The age, from 3 to 11 weeks, and gender-dependent
      expression of FMO1 and FMO3 in the rat liver and kidney were investigated. Based
      on the enzyme activities, protein levels and mRNA levels, this study demonstrates
      an important increase in the expression of the FMO3 in the liver of male rats
      during a period that corresponds to the acquisition of the sexual maturity. Rat
      liver FMO1 remains unchanged during this period of observation. The evolutions of
      both isoforms in the kidney of the male rat are similar to those observed in the
      liver. On the contrary, the important decrease in the total flavin-containing
      monooxygenase (FMO) activity observed in the liver of female rat is linked to a
      considerable decrease in the FMO1-dependent activity, FMO1 protein and FMO1 mRNA
      levels as a function of age. The expression of the FMO3 in the liver does not
      seem to be affected by the age of the female rat. Inversely, the expression of
      FMO1 in the female rat kidneys does not seem to be modified as a function of age
      while the expression of FMO3 is strongly increased.

PMID- 11996887
TI  - ESR analysis of spin adducts of alkoxyl and lipid-derived radicals with the spin
      trap Trazon.
AB  - Detection of oxygen-centered radicals was performed using the spin trap 1,3,3
      trimethyl-6-azabicyclo[3.2.1]oct-6-ene-N-oxide (Trazon), a bicyclic nitrone spin
      trap that is easily synthesized from the corresponding amine via hydrogen
      peroxide mediated oxidation in the presence of the catalyst, sodium tungstate.
      Compared to monocyclic spin traps such as 5,5-dimethyl-1-pyrroline N-oxide (DMPO)
      or 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO), the ESR spectra
      of Trazon spin adducts provide additional structural information due to long
      range hyperfine splitting constants and also due to the fact that different
      stereoisomers can be distinguished. This is especially helpful for the detection
      of lipid-derived alkoxyl radicals which can be identified according to their
      characteristic hyperfine splitting pattern. Due to the relatively high stability
      of the Trazon spin adducts with lipid alkoxyl radicals, which were formed from
      peroxidizing linoleic acid, ESR experiments could be performed using a stationary
      system, whereas a slow-flow system is recommended for DMPO. A series of
      structurally different alkoxyl radical adducts were synthesized by iron-catalyzed
      nucleophilic addition of the respective alcohol to the spin trap Trazon and the
      spectra were analyzed by computer simulation. Both the molecular weight of the
      alcohol and the position of the alcoholic hydroxyl group were of significant
      influence on the ESR spectra. Two stereochemically different spin adducts were
      formed in a ratio typical of the alcohol used, thus allowing structural
      classification of the alkoxyl radical trapped.

PMID- 11996888
TI  - Preferential efflux by P-glycoprotein, but not MRP1, of compounds containing a
      free electron donor amine.
AB  - Multidrug resistance (MDR) in model systems is known to be conferred by two
      different integral proteins, the 170-kDa P-glycoprotein (P-gp) and the 190-kDa
      multidrug resistance-associated protein (MRP1), both of which pump drugs out of
      MDR cells. The presence of a nitrogen atom, charged at physiological pH, has
      frequently been considered to be a hallmark of P-gp substrates and inhibitors.
      The present study was aimed at investigating the role of nitrogen in the ability
      of the pump to recognise substrate. We measured the kinetics of active efflux of
      seven new anthracycline derivatives in P-gp-expressing K562/ADR cells and in MRP1
      expressing GLC4/ADR cells. Six of these compounds represent analogues of
      daunorubicin in which the amino sugar nitrogen is bound to an amino- or a nitro
      substituted benzyl moiety, the seventh is a doxorubicin derivative in which
      benzyl group is bound with 4'-oxygen. We found that the compounds with a nitro
      group on the benzyl ring were poor substrates for P-gp despite the presence of a
      secondary amine that can be protonated. In contrast, compounds that have a free
      amino group were very good substrates even though this amine is not protonated in
      the pH range studied (pK approximately 3). These results show that the nitrogen
      atom does not interact with P-gp in a charged form but rather as an electron
      donating group.

PMID- 11996889
TI  - Ritonavir inhibition of calcium-activated neutral proteases.
AB  - Calpains (EC 3.4.22.17) are intracellular calcium-activated cysteine proteases
      that mediate tissue injury following post-ischemic and post-traumatic stress.
      Both human HIV protease and calpains share a similar secondary structure, where
      the active site is flanked by hydrophobic regions. The present study demonstrates
      that ritonavir, a hydrophobic HIV protease inhibitor, also inhibits calpain
      activity. In PC12 cell extracts assayed for calpain at maximal activity (2mM
      calcium), ritonavir exhibited competitive inhibition with a K(i) of 11+/-7.0
      microM. Experiments with purified enzymes showed inhibition for both m- and mu
      calpain isoforms (m-calpain, K(i)=9.2+/-1.2 microM; mu-calpain, K(i)=5.9+/-1.4
      microM). Ritonavir also inhibited calcium-stimulated calpain activity in PC12
      cells in situ. These results suggest that ritonavir or analogues of the drug
      should be investigated as cytoprotective agents in conditions where cell death or
      injury is mediated via calpain activation.

PMID- 11996890
TI  - Resistance of HepG2 cells against the adverse effects of ethanol related to
      neutral lipid and phospholipid metabolism.
AB  - The influence of both short- and long-term ethanol exposure on the lipid
      metabolism was determined in the human hepatoma cell line HepG2. Ethanol did not
      cause any cytotoxicity or lipid peroxidation even after 7 days of 100 mM ethanol
      treatment of HepG2 cells. Incubation of cells in the presence of [1-(14)C]ethanol
      demonstrated that these cells actively metabolize ethanol to acetyl CoA,
      incorporating the radioactive label into neutral lipids and phospholipids. [1,2,3
      (3)H]glycerol was efficiently used in phospholipid and neutral lipid
      biosynthesis, showing higher radioactivity in phosphatidylcholine,
      phosphatidylethanolamine and triacylglycerols. Exposure of HepG2 cells to 100 mM
      ethanol for 24 hr did not significantly modify the incorporation of glycerol into
      newly synthesized phospholipids and neutral lipids, nor was lipid degradation
      affected by the presence of ethanol. When the alcohol treatment was prolonged for
      7 days, incorporation of [1,2,3-(3)H]glycerol into triacylglycerols and
      diacylglycerols showed a slight increase concomitantly with decreased
      radioactivity in the major phospholipids, phosphatidylcholine and
      phosphatidylethanolamine. In addition, these changes were associated with a
      greater release of radiolabeled triacylglycerols into the culture medium. These
      results indicate that ethanol does not cause in HepG2 cells the marked lipogenic
      stimulation widely shown in hepatocytes, and demonstrate that HepG2 cells
      strongly resist the adverse effects of ethanol. Since these cells lack the
      isoenzymatic form of cytochrome P(450) mainly involved in the ethanol metabolism
      (namely cytochrome P(450)2E1) and also are devoid of alcohol dehydrogenase
      activity, we propose that the toxic actions of ethanol on liver must be linked to
      the activity of one or both of these systems.

PMID- 11996891
TI  - Modulation of pyridyl cyanoguanidine (CHS 828) induced cytotoxicity by 3
      aminobenzamide in U-937 GTB cells.
AB  - The role of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and the ADP
      ribosylation inhibitor 3-aminobenzamide (3-ABA) in the cytotoxicity induced by
      the novel antitumoral cyanoguanidine CHS 828 was investigated in the human
      lymphoma cell line U-937 GTB. Exposing cells to CHS 828 and 3-ABA in combination
      resulted in a 100-fold higher IC(50) compared to exposure to CHS 828 alone. CHS
      828 did not activate PARP, measured as PARP-activity and formation of poly(ADP
      ribose). The ATP-levels and levels of extracellular acidification rate of cells
      exposed to CHS 828 in combination with 3-ABA were maintained for a longer period
      than for cells exposed to CHS 828 alone. To characterize the mode of cell death,
      caspase-3 activity and gross morphology were assessed. 3-ABA increased and
      delayed the caspase-3 activity in cells exposed to CHS 828. Cells exposed to high
      concentrations of CHS 828 showed a necrotic morphology, while high concentrations
      of CHS 828 in combination with 3-ABA switched the mode of cell death, generating
      an apoptotic morphology. The results indicate that the cytotoxicity and
      morphology induced by CHS 828 is not due to PARP activation but can be modulated
      by the ADP-ribosylation inhibitor 3-ABA.

PMID- 11996892
TI  - Mitochondrial toxin inhibition of [(3)H]dopamine uptake into rat striatal
      synaptosomes.
AB  - Administration of the mitochondrial inhibitors malonate and 3-nitropropionic acid
      (3-NP) to rats provides useful models of Huntington's disease. Exposure to these
      inhibitors has been shown to result in increased extracellular concentrations of
      striatal dopamine (DA), which is neurotoxic at high concentrations. The cause of
      this increase is unknown. The purpose of this study was to determine whether
      mitochondrial inhibition alters dopamine transporter (DAT) function. Striatal
      synaptosomes were incubated in the presence of several structurally unrelated
      inhibitors of mitochondrial Complexes I, II, and IV, and [(3)H]DA uptake was
      measured. Although all of the toxins inhibited [(3)H]DA uptake, there was a large
      variation in their inhibitory potencies, the rank order being
      rotenone>>cyanide>azide>3-NP>>malonate. Examination of the kinetic parameters of
      [(3)H]DA uptake revealed that inhibition was due to a reduction in maximum
      velocity (V(max)), with no change in affinity (K(m)). The addition of either ATP
      or of ADP plus P(i) to synaptosomes treated with 3-NP, or of the reactive oxygen
      species spin trap alpha-phenyl-N-tert-butyl nitrone to synaptosomes exposed to
      either malonate or cyanide failed to prevent mitochondrial toxin-induced
      inhibition of DAT function. The lack of effect of high energy substrates or of a
      free radical scavenger suggests that the mechanism by which extracellular DA is
      increased by several mitochondrial toxins involves factors other than
      mitochondrial ATP production or oxidative stress. Taken together, the results
      suggest that one mechanism whereby mitochondrial toxins increase extracellular
      concentrations of DA is via interaction with the DAT at a site other than the
      substrate site, i.e. noncompetitive inhibition of the DAT.

PMID- 11996893
TI  - Neuronal cell death induced by antidepressants: lack of correlation with Egr-1,
      NF-kappa B and extracellular signal-regulated protein kinase activation.
AB  - The tricyclic antidepressants (TCA) amitriptyline and desipramine and the
      serotonin reuptake inhibitor fluoxetine induce, at microM concentrations, cell
      death in HT22 immortalized hippocampal neurons and PC12 pheochromocytoma cells.
      Here, we show that these neurotoxic effects are accompanied by a selective
      activation of extracellular signal-regulated protein kinase (ERK), the
      biosynthesis of the transcription factor Egr-1 and an increase in the
      transcriptional activity of NF-kappa B. However, an impairment of both ERK
      activation and Egr-1 biosynthesis by the MAP kinase kinase-1 (MEK-1) inhibitor
      PD98059 did not block cell death. Moreover, stimulation of ERK phosphorylation
      and Egr-1 biosynthesis by sphingosine-1-phosphate did not induce cell death,
      indicating that stimulation of the ERK signaling pathway and Egr-1 biosynthesis
      are not required for neuronal cell death induced by antidepressants. Likewise,
      attenuation of antidepressant-induced NF-kappa B activity by elevation of the
      intracellular cAMP concentration or by retroviral driven expression of the non
      degradable superrepressor I kappa B alpha S32A/S36A demonstrated that the
      elevation of NF-kappa B activity by amitriptyline, desipramine and fluoxetine is
      not an integral part of the apoptotic signaling cascade triggered by these
      compounds.

PMID- 11996894
TI  - Characterization of selective estrogen receptor modulator (SERM) activity in two
      triarylethylene oxybutyric acids.
AB  - Previously we identified 4-[1-(4-hydroxyphenyl)-2-phenylbuten-1-yl]phenoxy-n
      butyric acid (4HBA) and its des-hydroxy analog (BA) as potential selective
      estrogen receptor modulators (SERMs) in the ovariectomized (OVX) rat. The aim of
      the present study was to characterize comprehensively the effects of 4HBA and BA
      in both the OVX rat and in estrogen-responsive cells. Thus, 4HBA was found to be
      an estrogen antagonist with partial agonist efficacy in estrogen-responsive
      reporter gene and estrogen-dependent proliferation assays (MVLN cells and MCF-7
      human breast cancer cells, respectively). In the OVX rat, 4HBA and BA were
      equally effective and comparable to other known SERMs regarding (a) serum
      cholesterol reduction and suppression of serum markers of excessive bone
      metabolism, and (b) partial agonist efficacy in reproductive tissue relative to
      steroidal estrogens. Like steroidal estrogens, both compounds increased serum
      triglyceride levels, with BA being more effective in this regard. The maximal
      effects of 4HBA on all of these parameters except cholesterol lowering were seen
      at oral doses of 0.4 micromol/kg/day; maximal cholesterol lowering required doses
      of 10 micromol/kg/day. In OVX rat liver 9S fraction, BA was found to be
      efficiently converted to a single hydroxylated metabolite, 4HBA. These results
      suggest that the effects of BA in the OVX rat might, in part, be a consequence of
      biotransformation to 4HBA, and that those of 4HBA and BA in the OVX rat and in
      estrogen-responsive cells are qualitatively similar to those of SERMs such as
      tamoxifen and raloxifene.

PMID- 11996895
TI  - Comparison of inhibition of ovalbumin-induced bronchoconstriction in guinea pigs
      and in vitro inhibition of tumor necrosis factor-alpha formation with
      phosphodiesterase 4 (PDE4) selective inhibitors.
AB  - Phosphodiesterase 4 (PDE4) inhibitors elevate cyclic adenosine 5'-monophosphate
      (cAMP), and this elevation has been shown to inhibit inflammatory cytokines such
      as tumor necrosis factor-alpha (TNF-alpha). Using TNF-alpha as a biomarker, we
      have developed transcription-based assays to examine inhibition of PDE4 activity
      in human and guinea pig whole blood. In vitro inhibition by PDE4 inhibitors was
      measured using quantitative PCR (qPCR) analysis of TNF-alpha mRNA levels in whole
      blood stimulated with lipopolysaccharide (LPS). The kinetics of human TNF-alpha
      mRNA production were analyzed and shown to be highest 4 hr following LPS
      stimulation. The guinea pig displayed kinetics of TNF-alpha transcription similar
      to those of the human. Analysis of inhibition of human TNF-alpha protein
      production was performed by immunoassay and shown to correlate with inhibition of
      transcription for three of the four compounds tested. Roflumilast was found to be
      9-fold more potent for TNF-alpha inhibition in the qPCR assay than in the protein
      assay. The potencies of L-826,141 and roflumilast were determined in human and
      guinea pig whole blood by qPCR, with IC(50) values of 270 and 20 nM,
      respectively, in humans and 100 and 10 nM, respectively, in guinea pigs. These
      results show that the potency of PDE4 inhibitors can be monitored in whole blood
      using a transcription-based assay, and that this type of assay can be adapted to
      various species provided the TNF-alpha nucleotide sequence is known. The in vitro
      whole blood IC(50) for TNF-alpha inhibition was compared to inhibition in the
      ovalbumin-challenged guinea pig model of bronchoconstriction. Obtaining plasma
      levels at the IC(50) determined in vitro for L-826,141 and roflumilast provides
      significant inhibition of bronchoconstriction. This suggests that TNF-alpha can
      be used as a whole blood biomarker in the guinea pig for PDE4 inhibition in this
      inflammatory model.

PMID- 11996896
TI  - Pharmacological differences among CysLT(1) receptor antagonists with respect to
      LTC(4) and LTD(4) in human lung parenchyma.
AB  - We have previously reported, by means of equilibrium binding studies, the
      existence of two distinct binding sites with receptor characteristics for LTC(4)
      and LTD(4) in human lung parenchyma (HLP) membranes using S-decyl-glutathione (S
      decyl-GSH) to inhibit LTC(4) binding to a number of non-receptor sites. Recently,
      we have been able to avoid the use of S-decyl-GSH in kinetic experiments and to
      characterize a distinctive pharmacological profile for the LTC(4) high affinity
      binding sites which do not correlates with the ability of both LTD(4) and LTC(4)
      to contract isolated HLP strips through the CysLT(1) receptor. Here, we report
      that the most advanced CysLT(1) receptor antagonists, some of which are already
      in clinical use, displayed a different behavior toward LTC(4) and LTD(4) in HLP.
      Equilibrium and kinetic binding studies demonstrated the following rank order of
      potency for (3)H-LTD(4) receptor (CysLT(1)): zafirlukast = montelukast > LM-1507
      = LM-1484 = pranlukast. In addition, LM-1507, LM-1484, pranlukast and montelukast
      but not zafirlukast are able to interact also with the high affinity site for
      (3)H-LTC(4) (LM-1507 = LM-1484 > pranlukast; montelukast not detectable in the
      presence of S-decyl-GSH). In this respect, the behavior of the LM antagonists
      closely resembles that of pranlukast although LM-1507 and LM-1484 display a
      higher affinity for (3)H-LTC(4) sites. Montelukast has an intermediate behavior,
      inasmuch as its interaction with (3)H-LTC(4) sites can be revealed only in
      kinetic studies, while zafirlukast is totally unable to inhibit (3)H-LTC(4)
      binding. It might be, therefore, most relevant for a complete understanding of
      the clinical efficacy, besides their nominal potency, of the most advanced
      CysLT(1) receptor antagonists to consider their pharmacological differences with
      respect not only to LTD(4)/LTE(4), but also to LTC(4).

PMID- 11996897
TI  - Effects of Ca(2+) channel blockers on amiloride-sensitive Na(+) permeable
      channels and Na(+) transport in fetal rat alveolar type II epithelium.
AB  - A beta-adrenergic agonist (beta-agonist), terbutaline, stimulated amiloride
      sensitive Na(+) absorption in fetal rat alveolar type II epithelium, contributing
      to the clearance of lung fluid. Cytosolic Ca(2+) plays an important role in
      terbutaline-stimulated Na(+) absorption, since Ca(2+)-activated, amiloride
      sensitive Na(+)-permeable channels are involved in transcellular Na(+) absorption
      and terbutaline stably elevates the cytosolic Ca(2+) concentration by stimulating
      Ca(2+) influx. Therefore, we studied whether Ca(2+) channel blockers (Ni(2+),
      verapamil, and nifedipine) affect terbutaline-stimulated transcellular Na(+)
      absorption. Ni(2+) partially blocked the channel responsible for the terbutaline
      stimulated Na(+) absorption at the Na(+) entry pathway across the apical membrane
      of the epithelium, but did not diminish the terbutaline-stimulated transcellular
      Na(+) absorption. By measuring the capacity of the Na(+),K(+)-pump activity, we
      determined that the rate-limiting step of the terbutaline-stimulated
      transcellular Na(+) absorption was the extrusion step across the basolateral
      membrane by the Na(+),K(+)-pump. The other Ca(2+) channel blockers, verapamil and
      nifedipine, had effects identical to those of Ni(2+). Based upon these
      observations, we conclude that, in the beta-agonist-stimulated fetal rat alveolar
      type II epithelium, Ca(2+) channel blockers diminish amiloride-sensitive
      channels, but do not affect transcellular Na(+) absorption, since under the beta
      agonist-stimulated condition the Na(+),K(+)-pump is the rate-limiting step in
      Na(+) transport.

PMID- 11996898
TI  - Dapsone-induced cholestasis and impairment of bile salt output in the rat.
AB  - To evaluate the effect of dapsone (4,4'-diaminodiphenylsulfone, DDS) on biliary
      bile salt secretion, we administered the drug to male and female Wistar rats at a
      dose of 30 mg/kg body wt, twice a day, for 4 days. DDS decreased basal bile flow
      by about 20% in both male and female rats. In addition, basal biliary bile salt
      secretion was decreased by the drug in animals from both sexes (about 30%
      decrease). Bile salt maximum secretory rate, as evaluated by infusing
      tauroursodeoxycholate at stepwise-increasing rates, was not affected by DDS in
      either male or female rats, suggesting that the density of canalicular bile salt
      transporters is preserved. The size of the bile salt pool and the rate of de novo
      synthesis of bile salts, measured in bile salt-depleted animals, were decreased
      by about 33 and 35%, respectively; there was no difference in response between
      males and females. The ability of the ileum to reabsorb bile salts, as estimated
      by analysis of the expression of the ileal apical sodium-dependent bile salt
      transporter and of sodium taurocholate transport activity in brush border
      membrane vesicles, was not affected by DDS in either males or females. Overall,
      our findings suggest that an impairment of de novo synthesis mediated by a direct
      inhibition of CYP3A metabolism, rather than a decreased intestinal reabsorption
      of bile salts, accounts for the decrease in bile salt pool size. The dissociation
      between alteration of bile secretory function and the oxidative stress induced by
      DDS, which is known to be relevant only in male rats, is discussed.

PMID- 11996899
TI  - Uptake of (3)H-1-methyl-4-phenylpyridinium ((3)H-MPP(+)) by human intestinal Caco
      2 cells is regulated by phosphorylation/dephosphorylation mechanisms.
AB  - Several transmembrane transporters of organic compounds are regulated by
      phosphorylation/dephosphorylation mechanisms. The aim of this study was to
      investigate the possible regulation of the intestinal uptake of organic cations
      by these mechanisms. The intestinal apical uptake of 1-methyl-4-phenylpyridinium
      (MPP(+)) was studied by incubating Caco-2 cells at 37 degrees for 5 min with 200
      nM (3)H-MPP(+). Uptake of (3)H-MPP(+) by Caco-2 cells was not affected by
      activators of protein kinase G, and was not affected or slightly reduced (by 15
      20%) by activators of protein kinase A or protein kinase C. Uptake of (3)H-MPP(+)
      by Caco-2 cells was reduced in a concentration-dependent manner by non-selective
      phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine (IBMX), caffeine,
      teophylline). The IC(50) of IBMX was found to be 119 microM (102-138; n=9).
      Uptake of (3)H-MPP(+) by Caco-2 cells was not affected by inhibition of protein
      tyrosine kinase, but it was concentration-dependently reduced in the presence of
      inhibitors of mitogen-activated protein kinase. Uptake of (3)H-MPP(+) by Caco-2
      cells was strongly reduced by Ca(2+)/calmodulin-mediated pathway inhibitors, but
      it was not dependent on extracellular Ca(2+). Our results suggest that the
      intestinal apical uptake of MPP(+) is regulated by
      phosphorylation/dephosphorylation mechanisms, being most probably active in the
      dephosphorylated state. Moreover, uptake of (3)H-MPP(+) by Caco-2 cells and by
      the extraneuronal monoamine transporter (EMT) are regulated in a very similar
      manner, suggesting an important participation of EMT in the intestinal uptake of
      this compound.

PMID- 11996900
TI  - Verapamil decreases glucuronidase activity in the gut.
AB  - The present investigation addressed the role of verapamil for oral
      pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats
      received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1)
      verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1)
      morphine-hydrochloride) were also employed. Oral bioavailability of M6G and the
      fraction of M6G deglucuronidated to morphine were estimated from areas under the
      plasma-concentration vs. time curves (AUC) of morphine and its glucuronides. As
      initial results pointed towards inhibition of glucuronidases by verapamil, its
      capability to specifically inhibit E. coli and/or rat intestinal beta
      glucuronidase was assessed using altered cleavage of the model substrate 4
      methylumbelliferyl-beta-D-glucuronide (MUG). Oral bioavailability of M6G was
      2.1%; 13% of oral M6G was deglucuronidated to morphine. Co-administration of
      verapamil did not increase the AUC of M6G. AUCs of morphine and morphine-3
      glucuronide were smaller in the verapamil group than in controls. Verapamil co
      administration decreased the fraction of M6G deglucuronidated to morphine to
      4.6%. In vitro experiments provided evidence that verapamil inhibits beta
      glucuronidase from E. coli with an IC(50) of 30 microM, whereas no inhibition of
      the rat beta-glucuronidase from small intestine was seen. In conclusion,
      verapamil decreased intestinal deglucuronidation of M6G by inhibiting E. coli
      beta-glucuronidase. This indicates that verapamil is not suited as P-gp inhibitor
      in experiments involving glucuronides. An increase in the intestinal absorption
      of M6G due to P-gp-inhibition was not observed at the verapamil dose studied.

PMID- 11996901
TI  - Forty years of calcitonin--where are we now? A tribute to the work of Iain
      Macintyre, FRS.
AB  - Calcitonin was discovered as a hypocalcemic principal that was initially thought
      to originate from the parathyroid gland. This view was corrected subsequently,
      and an origin from the thyroid C cells was documented. The purification and
      sequencing of various calcitonins soon followed. Calcitonin is a 32-amino-acid
      long peptide with an N-terminal disulfide bridge and a C-terminal prolineamide
      residue. The peptide was shown to potently inhibit bone resorption; however, a
      direct osteoclastic action of the peptide was confirmed only in the early 1980s.
      Several osteoclast calcitonin receptors have subsequently been cloned and
      sequenced. Specific regions of the receptor necessary for ligand binding and
      intracellular signaling through cyclic AMP and calcium have been identified
      through systematic deletion mutagenesis and chimeric receptor studies.
      Calcitonin's potent antiresorptive effect has led to its use in treating Paget's
      disease of bone, osteoporosis, and hypercalcemia. This review retraces key
      aspects of the synthesis and structure of calcitonin, its cellular and molecular
      actions, and its therapeutic uses as they have emerged over the 40 years since
      its discovery. The review also examines the implications of these findings for
      future clinical applications as a tribute to early workers to whom credit must be
      given for creation of an important and expanding field. Notable are the new
      approaches currently being used to enhance calcitonin action, including novel
      allosteric activators of the calcitonin receptor, modulation of the release of
      endogenous calcitonin by calcimimetic agents, as well as the development of oral
      calcitonins.

PMID- 11996902
TI  - Zone-dependent changes in human vertebral trabecular bone: clinical implications.
AB  - We have previously shown that there are pronounced age-related changes in human
      vertebral cancellous bone density and microarchitecture. However, the magnitude
      of these changes seemed to be dependent on zone location in the vertebral body
      the central third vs. the areas adjacent to the endplates. The aim of the present
      study was, therefore, to investigate whether such zone-specific differences could
      be identified by static histomorphometric measures. The material comprised 48
      individuals (24 women aged 19-97 years, and 24 men aged 23-95 years). Three of
      the women had a known fracture of the L-2. From each L-2, thick frontal sections
      of half of the vertebra were embedded undecalcified in methylmethacrylate, cut
      into 10-microm-thick sections, and stained with aniline blue. The sections were
      scanned into a computer, and classic static histomorphometry was performed on the
      images. The histomorphometry was performed on both the whole section and on the
      separate zones (central and sub-endplate zone). The results showed that
      trabecular bone volume, trabecular number, and connectivity density decreased
      significantly faster with age, whereas marrow space star volume increased
      significantly faster with age in the zones adjacent to the endplates than in the
      central zone. The other histomorphometric measures showed no zone specificity in
      relation to aging. However, trabecular thickness and trabecular separation were
      both higher at all ages in the central zone than in the sub-endplate zone,
      although this was significant only for trabecular separation. The described
      differences might have significant clinical implications concerning quantitative
      computed tomography (QCT) scanning, X-ray analyses, and assessment of fracture
      liability in the human spine, but the underlying pathogenesis is still not known.
      This study shows that the human vertebral body can be described as two distinct
      zones with very specific age-related changes in density and microstructure. This
      zone-specificity is important for the correct interpretation of clinical data.

PMID- 11996903
TI  - Parathyroid hormone-related protein (PTHrP)-(1-139) isoform is efficiently
      secreted in vitro and enhances breast cancer metastasis to bone in vivo.
AB  - Parathyroid hormone-related peptide (PTHrP) is a mediator of local osteolysis due
      to breast cancer. Three isoforms of PTHrP, (1-139), (1-141), and (1-173), are
      products of alternative splicing in humans, but the specific contribution of each
      of these isoforms to osteolytic metastasis caused by breast cancer has not been
      evaluated. To determine the role of PTHrP isoforms in breast cancer metastasis to
      bone, the human breast cancer cell line MDA-MB-231 (MDA-231) was stably
      transfected with cDNAs for human prepro PTHrP-(1-139), -(1-141), or -(1-173).
      Stable MDA/PTHrP-(1-139) clones expressed more PTHrP mRNA and secreted more PTHrP
      protein, compared with MDA/PTHrP-(1-141), -(1-173), or parental MDA-231. Parental
      MDA-231 cells and clones expressing each isoform had similar growth rates in
      vitro. In a mouse model of bone metastases, the osteolytic lesion area of
      radiographs was greatest in mice bearing MDA/PTHrP-(1-139) compared with those
      bearing MDA/PTHrP-(1-141), -(1-173), or parental MDA-231. Ca(++) and plasma PTHrP
      concentrations were significantly higher in the MDA/PTHrP-(1-139) compared with
      the MDA/PTHrP-(1-141), -(1-173), or parental MDA-231 groups. These data
      demonstrate that the PTHrP-(1-139) isoform was produced to a greater extent than
      PTHrP-(1-141) or -(1-173), and in vivo enhanced osteolysis with increased plasma
      PTHrP concentrations and hypercalcemia compared with overexpression of PTHrP-(1
      141) or -(1-173).

PMID- 11996904
TI  - Parathyroid hormone induces RGS-2 expression by a cyclic adenosine 3',5'
      monophosphate-mediated pathway in primary neonatal murine osteoblasts.
AB  - Parathyroid hormone (PTH) is a promising anabolic agent for the treatment of
      osteoporosis. However, PTH is also potently catabolic. To help delineate the
      molecular mediators of PTH's opposing effects on skeletal metabolism, we have
      examined PTH-induced regulator of G-protein signaling-2 (RGS-2) expression and
      function in murine osteoblasts. RGS proteins are GTPase-activating proteins
      (GAPs) that regulate GTP-binding protein-coupled receptor (GPCR) signaling by
      enhancing the intrinsic GTPase activity of Galpha subunits. We found that 10
      nmol/L PTH maximally induced RGS-2 mRNA in murine MC3T3-E1 cells, rat Py1a and
      ROS-17/2.8 cells, primary mouse osteoblasts (MOB cells), and mouse calvariae
      organ culture at 1-2 h posttreatment. PTH signaling through its receptor, PTHR1,
      is coupled to cAMP-protein kinase A (PKA), protein kinase C (PKC), and calcium
      signaling pathways. We examined the effect of selective signaling agonists and
      antagonists on RGS-2 expression in MOB cells to determine which pathway(s)
      mediates PTH-induced RGS-2 expression. Although selective activation of all three
      pathways led to RGS-2 expression, cAMP-PKA activation with 10 nmol/L PTH and 10
      micromol/L forskolin elicited the strongest induction. Similarly, RGS-2 mRNA
      expression was most strongly inhibited by the PKA inhibitor, H89 (10-30
      micromol/L). The phorbol ester, PMA (1 micromol/L), which activates the PKC
      pathway, and ionomycin (1 micromol/L), which activates the calcium pathway,
      produced small but detectable elevations in RGS-2 mRNA levels. Overnight
      treatment with 1 micromol/L PMA to deplete PKC did not affect subsequent RGS-2
      induction by PTH, but significantly inhibited PMA-induced RGS-2 expression.
      Treatment with 1-100 nmol/L PTH(3-34), which does not activate cAMP-PKA
      signaling, did not induce RGS-2 expression. MOB cells pretreated with 3 microg/mL
      cycloheximide produced sustained RGS-2 mRNA levels 2 h after 10 nmol/L PTH
      treatment. Actinomycin D (5 microg/mL) completely blocked 10 nmol/L PTH-induced
      RGS-2 expression. Finally, we tested the effect of RGS-2 overexpression on PTH-
      and fluprostenol-induced interleukin (IL)-6 promoter activity in MOB cells. PTH
      induces IL-6 through PKA activation, whereas fluprostenol induces IL-6 through
      PKC activation. We found that RGS-2 overexpression significantly inhibited IL-6
      promoter activity following fluprostenol treatment, but not following PTH
      treatment. We conclude that RGS-2 is a PTH-induced primary response gene in
      murine osteoblasts that is induced mainly through the cAMP-PKA pathway and
      specifically inhibits Galphaq-coupled receptors.

PMID- 11996905
TI  - Effects of cortisol and bone morphogenetic protein-2 on stromal cell
      differentiation: correlation with CCAAT-enhancer binding protein expression.
AB  - Bone marrow stroma contain pluripotential cells with the potential to
      differentiate into various mesenchymal cell lineages. We compared the effect of
      cortisol and bone morphogenetic protein-2 (BMP-2) on the differentiation of
      murine ST-2 stromal cells into mature osteoblasts or adipocytes. ST-2 cells were
      cultured for 3-27 days in the presence of 10% fetal bovine serum, 100 microg/mL
      ascorbic acid, and 5 mmol/L beta-glycerolphosphate in the presence or absence of
      cortisol at 1 micromol/L or BMP-2 at 1 nmol/L. Untreated ST-2 cells expressed
      high levels of alkaline phosphatase activity (APA) 15 days after confluence, and
      this was followed by the appearance of mineralized nodules after 24 days. BMP-2
      accelerated and intensified the appearance of cells expressing APA and the
      presence of mineralized nodules. In contrast, cortisol decreased APA, prevented
      the formation of mineralized nodules, and induced a cellular phenotype
      characteristic of adipocytes. Untreated stromal cells expressed osteocalcin,
      Cbfa1, type I collagen, and alkaline phosphatase mRNA. BMP-2 increased
      osteocalcin and alkaline phosphatase mRNA, whereas cortisol suppressed their
      expression, as well as Cbfa1 and type I collagen transcripts. Cortisol enhanced,
      and BMP-2 downregulated, peroxisome proliferator-activated receptor gamma 2 and
      adipsin transcripts. The C/EBP transcription factors regulate genes critical for
      adipocytic and osteoblastic differentiation. Cortisol increased the expression of
      C/EBP alpha, beta, delta, and gamma mRNA levels, whereas BMP-2 had minor effects
      on C/EBP expression. In conclusion, BMP-2 accelerates the differentiation of
      stromal cells toward an osteoblastic phenotype, whereas glucocorticoids induce
      their differentiation toward an adipocytic phenotype.

PMID- 11996906
TI  - Alterations in the growth plate cartilage of rats with renal failure receiving
      corticosteroid therapy.
AB  - Growth retardation is a complication often associated with corticosteroid
      therapy. Corticosteroids are frequently used in the treatment of children with
      chronic renal failure. To examine the effects of corticosteroids on the growth
      plate cartilage in renal failure, selected markers of chondrocyte function and
      phenotype were evaluated in the proximal tibia of subtotally nephrectomized rats
      treated with corticosteroid. Serum parathyroid hormone (PTH), urea nitrogen, and
      creatinine levels were higher in the nephrectomized animals. Weight gain was less
      in the corticosteroid-treated animals; however, linear growth and tibial length
      did not differ among the groups after 10 days of corticosteroid therapy. The
      total width of the growth plate and the width of the proliferative zone were much
      smaller in corticosteroid-treated nephrectomized (Nx-MP) animals. Type II
      collagen mRNA expression was lower in animals treated with corticosteroids, and
      proliferating-cell nuclear antigen staining, histone-4, and insulin-like growth
      factor-1 (IGF-1)-receptor mRNA expression were further decreased in the Nx-MP
      group. There was an increase in TUNEL-positive cells in the corticosteroid
      treated rats with normal renal function (intact-MP), associated with an increase
      in Bax and a decrease in Bcl-2 protein expression. In the Nx-MP group, both Bax
      and Bcl-2 protein staining was much less frequent, and TUNEL-positive cells were
      lower in number compared with the intact-MP group. Vascular endothelial growth
      factor expression in the hypertrophic chondrocytes was lower in corticosteroid
      treated animals. There was less gelatinase B/matrix metalloproteinase-9
      expression in the Nx-MP group, which was not associated with a decrease in
      tartrate-resistant acid phosphatase (TRAP) staining in the chondro-osseous
      junction. Inhibition of chondrocyte proliferation, diminishing of apoptosis, and
      lower angiogenic activity may contribute to the alterations in growth plate
      architecture and the significant reduction in growth plate width in rats with
      renal failure receiving corticosteroid therapy.

PMID- 11996907
TI  - Stem cell characteristics of human trabecular bone-derived cells.
AB  - Human trabecular bone-derived cells (HTBs) have been used for many years as
      osteoblast progenitors. In this study we tested whether HTBs have stem cell
      characteristics; that is, whether they are pluripotent and able to self-renew. We
      show that HTBs readily differentiate into osteoblasts, chondrocytes, and
      adipocytes if subjected to the appropriate differentiating conditions.
      Importantly, differentiation into these three lineages is maintained in single
      cell clones derived by limiting dilution, following expansion over more than 20
      cumulative population doublings. We conclude that cultures of HTBs are equivalent
      to cultures of "mesenchymal stem cells" (MSCs) isolated from bone marrow.

PMID- 11996908
TI  - Bone cell mitogenic action of fluoroaluminate and aluminum fluoride but not that
      of sodium fluoride involves upregulation of the insulin-like growth factor
      system.
AB  - The fluoroaluminate (AlF(4)(-)) ion and sodium fluoride (NaF) have previously
      been shown to be bone cell mitogens. This study sought to determine whether the
      bone cell mitogenic action of AlF(4)(-) and/or NaF would involve the insulin-like
      growth factor (IGF) regulatory system. We evaluated the effect of mitogenic doses
      of AlF(4)(-) and NaF on the mRNA levels and the protein level (in conditioned
      media [CM]) of several components of the IGF system (i.e., IGF-2, IGF binding
      protein [IGFBP]-4, and IGFBP-5) in human TE85 osteosarcoma cells. Aluminum
      fluoride (AlF(3)) was included for comparison. NaF, AlF(3), and AlF(4)(-), each
      at 50-100 micromol/L, increased [3H]thymidine incorporation in TE85 cells.
      Mitogenic concentrations of AlF(3) and AlF(4)(-): (1) increased the mRNA (up to
      twofold after 24 h treatment) and protein (in CM) levels (up to 2.5-fold after 48
      h treatment) of IGF-2; (2) increased the mRNA level (twofold) and the protein
      level in CM (up to threefold) of stimulatory IGFBP-5; and (3) either reduced
      slightly or had no effect on the mRNA and protein (in CM) levels of the
      inhibitory IGFBP-4. Conversely, mitogenic concentrations of NaF had no
      significant effects on the protein (in CM) or mRNA level of IGF-2, IGFBP-4, or
      IGFBP-5. The addition of an inhibitory concentration of IGFBP-4 completely
      abolished the bone cell mitogenic activity of AlF(3) and AlF(4)(-) but not that
      of NaF. The findings of this study provide strong evidence that the bone cell
      mitogenic activity of AlF(4)(-) and AlF(3), but not that of NaF, is mediated by
      the upregulation of the IGF regulatory system.

PMID- 11996909
TI  - Establishment of human cementifying fibroma cell lines by transfection with
      temperature-sensitive simian virus-40 T-antigen gene and hTERT gene.
AB  - Human cementifying fibroma (HCF) is a benign fibro-osseous neoplasm of
      periodontal ligament (PDL) origin containing varying amounts of mineralized
      material resembling cementum. In the present study, we established cell lines
      from HCF, which were detected in the mandible of a 54-year-old Japanese man. To
      obtain immortalized cell clones, we undertook transfection with temperature
      sensitive simian virus-40 (SV40) T-antigen and hTERT into HCF cells. Cells
      transfected with SV40 T-antigen entered "crisis" state between passages 22 and
      35, but activation of telomerase by transfection with hTERT in the SV40
      transformed HCF cells resulted in bypass of the crisis and maintenance over
      passage 200. HCF cell lines decreased the expression of SV40 T-antigen and the
      activity of cell proliferation at a nonpermissive temperature (39 degrees C) in
      comparison with that at a permissive temperature (33 degrees C). High activities
      of alkaline phosphatase and mineralization and the expression of type I collagen,
      osteocalcin, osteopontin, and bone sialoprotein by reverse transcription
      polymerase chain reaction (RT-PCR) were observed in HCF cells at 39 degrees C.
      Overall, these findings suggest that: (i) HCF cell lines may represent a novel in
      vitro human cell model for the study of the regulatory mechanism of
      differentiation and proliferation of the human PDL; and (ii) transfection of
      plasmids encoding the temperature-sensitive SV40 T-antigen gene and hTERT gene
      may be useful for obtaining immortalized cell lines from benign human tumor and,
      probably, nonneoplastic human tissues.

PMID- 11996910
TI  - Three-dimensional cultures of normal human osteoblasts: proliferation and
      differentiation potential in vitro and upon ectopic implantation in nude mice.
AB  - We report the establishment in vitro of three-dimensional (3D) cultures of human
      osteoblasts (hOB) derived from normal adults and supported uniquely by the
      extracellular matrix (ECM) they deposit. Osteoblasts were cultured in 3D cultures
      in vitro for up to 120 days. The 3D cultures, examined at 25, 31, and 48 days,
      expressed protein markers of osteoblastic cells, namely osteonectin, collagen
      type I, fibronectin, osteopontin, bone sialoprotein, biglycan, and decorin.
      Sequentially, alkaline phosphatase (AP) and then Ca incorporation, mineralization
      of matrix (monitored by histochemistry and transmission electron microscopy), and
      finally osteocalcin expression, were detected in the 3D cultures.
      Ultrastructurally, morphology progressed from early to mature osteoblast and to
      osteocyte-like. Cells were embedded in a matrix with organized collagen type I
      fibers containing, increasingly with time of culture, needle-shaped crystals,
      often associated with matrix vesicles, characteristic of those in bone. During
      the culture (up to 120 days) there was an outgrowth of proliferating osteogenic
      cells from the 3D structure. Subcutaneous implantation in nude mice for 20 days
      of osteoblasts cultured in 3D culture for different lengths of time in vitro,
      showed progression of mineralization from the inner region of the implant
      outward, with peripheral cells being embedded in nonmineralized, collagen-rich
      matrix. The 3D implants were invaded by vessels derived from the host.

PMID- 11996911
TI  - Platelet-released supernatants stimulate formation of osteoclast-like cells
      through a prostaglandin/RANKL-dependent mechanism.
AB  - Platelets are activated at fracture sites or upon the insertion of implants as a
      consequence of vascular disruption and secrete the contents of their granules
      into the developing hematoma. The regeneration of injured tissue requires bone
      remodeling and the resorbing activity of osteoclasts. To test our hypothesis that
      platelets can stimulate osteoclastogenesis, we examined the effects of
      supernatants released from thrombin-activated platelets on osteoclast-like cell
      formation in murine bone marrow cultures. Histochemical analysis indicated the
      presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive
      multinucleated cells. Transcripts that are characteristically expressed in native
      osteoclasts were increased in these cultures, as determined by semiquantitative
      reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition
      of both cyclooxygenases with indomethacin, as well as the addition of the
      cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked
      osteoclast-like cell formation and decreased endogenous prostaglandin E(2)
      production. Platelet-released supernatants stimulated the expression of receptor
      activator of NF-kappaB ligand (RANKL), whereas mRNA levels of osteoprotegerin
      (OPG) were decreased. The formation of osteoclast-like cells was prevented by
      recombinant OPG. Our results suggest that COX-2 activity is necessary for
      osteoclast-like cell formation in response to platelet-released supernatants, and
      that endogenously produced prostaglandin E(2) can, in turn, increase the
      RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by
      stimulation of osteoclastogenesis.

PMID- 11996912
TI  - The effect of growth/differentiation factor-5 deficiency on femoral composition
      and mechanical behavior in mice.
AB  - A subclass of the bone morphogenetic proteins (BMPs), known as
      growth/differentiation factors (GDFs) 5, 6, and 7, have been shown to affect
      several skeletal processes, including endochondral ossification, synovial joint
      formation, and tendon and ligament repair. Mice deficient in GDF-5 have also been
      shown to exhibit biomechanical abnormalities in tendon that may be associated
      with altered type I collagen. The purpose of this study was to investigate the
      effect of GDF-5 deficiency on another type I collagen-rich tissue: cortical bone.
      Analyses were performed on femora from 8-week-old GDF-5-deficient male
      brachypodism mice. We hypothesized that GDF-5-deficient bones would exhibit
      altered geometric, structural, and material properties compared with control
      littermates. Mutant animals were significantly smaller in body mass than controls
      (-21%). Geometrically, mutant long bones were significantly shorter (-25%), had a
      lower polar moment of inertia (-34%), and a lower geometric strength indicator
      (analogous to the section modulus of a circular section) (-30%). When normalized
      by body mass, however, geometric differences were no longer significant.
      Structurally, GDF-5-deficient femora were weaker (-31%) and more compliant (-57%)
      than controls when tested to failure in torsion. Lower bone structural stiffness
      in the mutants was not completely explained by the smaller bone geometry, because
      mutant bones exhibited a significantly lower effective shear modulus (-36%).
      Although body mass did not fully explain the reduced structural strength in
      mutant bones, strength differences were adequately explained by bone cross
      sectional geometry; maximum effective shear stress was not significantly
      different between mutants and controls, despite a statistically significant 6%
      lower ash fraction in mutant femora. No significant difference was detected in
      collagen content, as indicated by hydroxyproline per dry mass.

PMID- 11996913
TI  - Expression of smooth muscle actin in connective tissue cells participating in
      fracture healing in a murine model.
AB  - The role of alpha-smooth muscle actin (SMA)-expressing fibroblasts in the
      contraction of skin wounds has been known for three decades. Recent studies have
      demonstrated that osteoblasts can also express the gene for this contractile
      muscle actin isoform and can contract a collagen-glycosaminoglycan analog of
      extracellular matrix in vitro. These findings provided rationale for the
      hypothesis that SMA-expressing cells contribute to fracture healing by drawing
      the bone ends together. To begin to test this hypothesis, immunohistochemistry
      was employed to evaluate the distribution of connective tissue cells expressing
      SMA in a mouse model of successful fracture healing. The results demonstrated
      that the majority of the cells comprising the mesenchymal tissue interposed
      between the fracture ends contained SMA after 7 and 21 days, supporting the
      working hypothesis. Most of the osteoblasts lining the surfaces of newly forming
      bone and the chondrocytes comprising the cartilaginous callus also expressed this
      contractile actin isoform. The maximal SMA expression extended from 7 to 21 days
      postfracture. The finding of high levels of SMA expression in connective tissue
      cells participating in fracture healing suggests that SMA-enabled contraction may
      be playing a role in the healing process. These results warrant further study of
      the specific SMA-dependent cell behavior.

PMID- 11996914
TI  - A potent small molecule, nonpeptide inhibitor of cathepsin K (SB 331750) prevents
      bone matrix resorption in the ovariectomized rat.
AB  - Inhibition of the cyteine proteinase, cathepsin K (E.C. 3.4.22.38) has been
      postulated as a means to control osteoclast-mediated bone resorption. The
      preferred animal models for evaluation of antiresorptive activity are in the rat.
      However, the development of compounds that inhibit rat cathepsin K has proven
      difficult because the human and rat enzymes differ in key residues in the active
      site. In this study, a potent, nonpeptide inhibitor of rat cathepsin K (K(i) =
      4.7 nmol/L), 5-(2-morpholin-4-yl-ethoxy)-benzofuran-2-carboxylic acid ((S)-3
      methyl-1-(3-oxo-1-[2-(3-pyridin-2-yl-phenyl)-ethenoyl]-azepan-4-ylcarbanoyl)
      butyl)-amide (SB 331750), is described, which is efficacious in rat models of
      bone resorption. SB 331750 potently inhibited human cathepsin K activity in vitro
      (K(i) = 0.0048 nmol/L) and was selective for human cathepsin K vs. cathepsins B
      (K(i) = 100 nmol/L), L (0.48 nmol/L), or S (K(i) = 14.3 nmol/L). In an in situ
      enzyme assay, SB 331750 inhibited osteoclast-associated cathepsin activity in
      tissue sections containing human osteoclasts (IC(50) approximately 60 nmol/L) and
      this translated into potent inhibition of human osteoclast-mediated bone
      resorption in vitro (IC(50) approximately 30 nmol/L). In vitro, SB 331750
      partially, but dose-dependently, prevented the parathyroid hormone-induced
      hypercalcemia in an acute rat model of bone resorption. To evaluate the ability
      of SB 331750 to inhibit bone matrix degradation in vivo, it was administered for
      4 weeks at 3, 10, or 30 mg/kg, intraperitoneally (i.p.), u.i.d. in the
      ovariectomized (ovx) rat. Both 10 and 30 mg/kg doses of compound prevented the
      ovx-induced elevation in urinary deoxypyridinoline and prevented the ovx-induced
      increase in percent eroded perimeter. Histological evaluation of the bones from
      compound-treated animals indicated that SB 331750 retarded bone matrix
      degradation in vivo at all three doses. The inhibition of bone resorption at the
      10 and 30 mg/kg doses resulted in prevention of the ovx-induced reduction in
      percent trabecular area, trabecular number, and increase in trabecular spacing.
      These effects on bone resorption were also reflected in inhibition of the ovx
      induced loss in trabecular bone volume as assessed using microcomputerized
      tomography (microCT; approximately 60% at 30 mg/kg). Together, these data
      indicate that the cathepsin K inhibitor, SB 331750, prevented bone resorption in
      vivo and this inhibition resulted in prevention of ovariectomy-induced loss in
      trabecular structure.

PMID- 11996915
TI  - Optimal age for preventing osteoporosis after menopause depends on effects of
      stopping treatment.
AB  - The aim of this study was to model the effect of short (3 year) treatments for
      osteoporosis at different times after menopause on the risk of osteoporotic
      fracture and to assess the impact of strategies to target high-risk individuals.
      Treatment efficacy for hip, proximal forearm, shoulder, and spine fracture were
      computed from the relationship between bone mineral density (BMD) and fracture in
      women from Sweden. Treatment that increased hip bone mineral density by 6% over
      untreated women saved 126 vertebral, hip, proximal humerus, and forearm fractures
      per 1000 women at the age of 50 years, provided that the effects of treatment
      persisted. Targeting women with osteoporosis at this age would save an additional
      50% of fractures. With age, the number of fractures saved decreased moderately.
      At the age of 70 years, 133 fractures would be saved in women with osteoporosis
      compared to 198 in women with osteoporosis at the age of 50 years. Where the
      effect of treatment was assumed to wear off over 20 years after stopping
      treatment, the efficacy of treatment was reduced at all ages, but most markedly
      at the age of 50 years. Where all women aged 50 years were treated, the number of
      fractures saved per 1000 women decreased from 127 to 15 and, in the case of
      targeting women with osteoporosis, decreased from 198 to 27 per 1000 women. By
      contrast, with a persisting effect of treatment, the number of fractures saved
      increased markedly with advancing age. If all women were targeted at the age of
      50 years, 15 fractures would be saved, whereas this increased to 55 per 1000
      women at the age of 70 years. When treatment effects wore off more rapidly with
      an offset half-time of 2.5 years only 5 fractures were saved per 1000 women at
      the age of 50 years. This figure rose to 23 per 1000 at the age of 70 years. We
      conclude that, although uncertainty exists concerning the offset of effect of
      treatments, treatments should be optimally given to women without prior fractures
      in later life.

PMID- 11996916
TI  - Cancellous bone mechanical properties from normals and patients with hip
      fractures differ on the structure level, not on the bone hard tissue level.
AB  - Osteoporosis is currently defined in terms of low bone mass. However, the source
      of fragility leading to fracture has not been adequately described. In
      particular, the contributions of bone tissue properties and architecture to the
      risk or incidence of fracture are poorly understood. In an earlier experimental
      study, it was found that the architectural anisotropy of cancellous bone from the
      femoral heads of fracture patients was significantly increased compared with age-
      and density-matched control material (Ciarelli et al., J Bone Miner Res 15:32-40;
      2000). Using a combination of compression testing and micro-finite element
      analysis on a subset of cancellous bone specimens from that study, we calculated
      the hard tissue mechanical properties and the apparent (macroscopic) mechanical
      properties. The tissue modulus was 10.0 GPa (SD 2.2) for the control group and
      10.8 GPa (SD 3.3) for the fracture group (not significant). There were no
      differences in either the apparent yield strains, percentages of highly strained
      tissue, or the relationship between apparent yield stress and apparent elastic
      modulus. Hence, a difference in the tissue yield properties is unlikely. At the
      apparent level, the fracture group had a significantly decreased transverse
      stiffness, resulting in increased mechanical anisotropy. These changes suggest
      that bone in the fracture group was "overadapted" to the primary load axis, at
      the cost of fragility in the transverse direction. We conclude that individuals
      with a history of osteoporotic fractures do not have weaker bone tissue.
      Architectural and mechanical anisotropy alone renders their bone weaker in the
      nonprimary loading direction.

PMID- 11996917
TI  - Development of the femoral bicondylar angle in hominid bipedalism.
AB  - The bicondylar angle is the angle between the diaphysis of the femur and a line
      perpendicular to the infracondylar plane. The presence of a femoral bicondylar
      angle in Australopithecus afarensis indicates that these 3.5-million-year-old
      hominids were bipedal. Many studies have linked the formation of the femoral
      bicondylar angle with bipedality, but the mechanism for the formation of the
      angle is poorly understood. Mechanical factors, such as stresses and strains,
      influence the growth process. In particular, previous studies have demonstrated
      that hydrostatic compressive stress inhibits growth and ossification, and
      octahedral shear stress promotes growth and ossification. In this study we
      implemented these mechanobiological principles in a three-dimensional finite
      element model of the distal femur. We applied loading conditions to the model to
      simulate loading during the single-leg stance phase of bipedal gait. The stresses
      in the physis of the distal femur that result from bipedal loading conditions
      promote growth and ossification more on the medial side than on the lateral side
      of the femur, forming the bicondylar angle. This model explains the presence of
      the bicondylar angle in hominid bipedalism and also the ontogenetic development
      of the bicondylar angle in growing children. The mechanobiological relationship
      between endochondral ossification and mechanical loading provides valuable
      insight into bone development and morphology.

PMID- 11996918
TI  - Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal
      subpopulations from NHANES III.
AB  - Subclinical vitamin D deficiency may be common in certain subgroups in the U.S.,
      but to date vitamin D data from other groups in the population have not been
      available. We used serum 25-hydroxyvitamin D (25-OHD) data from 18,875
      individuals examined in the Third National Health and Nutrition Examination
      Survey (NHANES III 1988-1994) to assess the vitamin D status of selected groups
      of the noninstitutionalized U.S. adolescent and adult population. Serum 25-OHD
      levels were measured by a radioimmunoassay kit (DiaSorin, Inc., Stillwater, MN;
      normal range 22.5-94 nmol/L). Because physical exams are performed in mobile vans
      in NHANES, data could not be collected in northern latitudes during the winter;
      instead data were collected in northern latitudes during summer and in southern
      latitudes in winter. To address this season-latitude aspect of the NHANES design,
      we stratified the sample into two seasonal subpopulations (winter/lower latitude
      and summer/higher latitude) before examining vitamin D status. Less than 1% of
      the winter/lower latitude subpopulation had vitamin D deficiency (25-OHD <17.5
      nmol/L). However, the prevalence of vitamin D insufficiency in this group ranged
      from 1%-5% with 25-OHD <25 nmol/L to 25%-57% with 25-OHD <62.5 nmol/L, even
      though the median latitude for this subsample (32 degrees N) was considerably
      lower than the latitude at which vitamin D is not synthesized during winter
      months (approximately 42 degrees N). With the exception of elderly women,
      prevalence rates of vitamin D insufficiency were lower in the summer/higher
      latitude subpopulation (<1%-3% with 25-OHD <25 nmol/L to 21%-49% with 25-OHD
      <62.5 nmol/L). Mean 25-OHD levels were highest in non-Hispanic whites,
      intermediate in Mexican Americans, and lowest in non-Hispanic blacks. Our
      findings suggest that vitamin D deficiency is unlikely in the two seasonal
      subpopulations of noninstitutionalized adolescents and adults that can be validly
      assessed in NHANES III. However, vitamin D insufficiency is more common in these
      two seasonal subpopulations. Of particular interest is that insufficiency
      occurred fairly frequently in younger individuals, especially in the winter/lower
      latitude subsample. Our findings support continued monitoring of this vitamin in
      the U.S. population.

PMID- 11996920
TI  - Effects of biomechanical stress on bones in animals.
AB  - The signals that allow bone to adapt to its mechanical environment most likely
      involve strain-mediated fluid flow through the canalicular channels. Fluid can
      only be moved through bone by cyclic loading, and the shear stresses generated on
      bone cells are proportional to the rate of loading. The proportional relation
      between fluid shear stresses on cells and loading rate predicts that the
      magnitude of bone's adaptive response to loading should be proportional to strain
      rate. For lower loading frequencies within the physiologic range, experimental
      evidence shows this is true. It is also true that the mechanical sensitivity of
      bone cells saturates quickly, and that a period of recovery either between
      loading cycles or between periods of exercise can optimize adaptive response.
      Together, these concepts suggest that short periods of exercise, with a 4-8 h
      rest period between them, are a more effective osteogenic stimulus than a single
      sustained session of exercise. The data also suggest that activities involving
      higher loading rates are more effective for increasing bone formation, even if
      the duration of the activity is short.

PMID- 11996921
TI  - Methodology of activity surveys to estimate mechanical loading on bones in
      humans.

PMID- 11996922
TI  - Relationship between physical activity and bone mineral status in young adults:
      the Northern Ireland Young Hearts Project.
AB  - Physical activity during the first three decades of life may increase peak bone
      mass and reduce future osteoporosis risk. The aim of this study was to determine
      the extent to which different components of physical activity may influence bone
      mineral status within a representative population sample of young men and women.
      Bone mineral density (BMD) and content (BMC) were determined at the lumbar spine
      and femoral neck in 242 men and 212 women, aged 20-25 years, by dual-energy X-ray
      absorptiometry. Physical activity was assessed by a self-report questionnaire
      designed to measure the frequency and duration of physical activity and its
      components (i.e., work, non-sports leisure, sports-related activities, and peak
      strain sports activities). Potential confounding factors such as height, weight,
      diet, and smoking habits were also assessed. In multivariate linear regression
      models, sports activity and peak strain sports activity undertaken by men were
      strongly associated with both lumbar spine BMD (beta = 0.35 [0.21, 0.49] and beta
      = 0.31 [0.17, 0.44], respectively) and BMC (beta = 0.33 [0.21, 0.45] and beta =
      0.26 [0.14, 0.38], respectively) and femoral neck BMD (beta = 0.35 [0.21, 0.48]
      and beta = 0.27 [0.14, 0.40], respectively) and BMC (beta = 0.32 [0.19, 0.44] and
      beta = 0.29 [0.17, 0.41], respectively) (all p < 0.01), but work and non-sports
      leisure activities were not. In women, there were no associations between bone
      measurements and any component of physical activity. In models involving all
      subjects the gender/sports activity, but not the gender/peak strain, interaction
      term was statistically significant. Sports activity explained 10.4% of the
      observed variance in lumbar spine BMD in men, but <1% in women. These results
      demonstrate the importance of sports activities, especially those involving high
      peak strain, in determining peak bone status in young men. Failure to observe
      this association in women reflects their lower participation in such activities,
      but they may have the same capacity to benefit from these activities as men.
      Intervention studies are warranted to determine whether peak bone density in
      women can be improved by participating, during childhood and adolescence, in
      sports activities involving high peak strain.

PMID- 11996923
TI  - Validation of a physical activity questionnaire to measure the effect of
      mechanical strain on bone mass.
AB  - Most of the questionnaires available to estimate the daily physical activity
      levels of humans are based on measuring the intensity of these activities as
      multiples of resting metabolic rate (METs). Metabolic intensity of physical
      activities is the most important component for evaluating effects on
      cardiopulmonary fitness. However, animal studies have indicated that for effects
      on bone mass the intensity in terms of energy expenditure (metabolic component)
      of physical activities is less important than the intensity of mechanical strain
      in terms of the forces by the skeletal muscles and/or the ground reaction forces.
      The physical activity questionnaire (PAQ) used in the Amsterdam Growth and Health
      Longitudinal Study (AGAHLS) was applied to investigate the long-term effects of
      habitual physical activity patterns during youth on health and fitness in later
      adulthood. The PAQ estimates both the metabolic components of physical activities
      (METPA) and the mechanical components of physical activities (MECHPA).
      Longitudinal measurements of METPA and MECHPA were made in a young population of
      males and females ranging in age from 13 to 32 years. This enabled evaluation of
      the differential effects of physical activities during adolescence (13-16 years),
      young adulthood (21-28 years), and the total period of 15 years (age 13-28 years)
      on bone mineral density (BMD) of the lumbar spine, as measured by dual-energy X
      ray absorptiometry (DXA) in males (n = 139) and females (n = 163) at a mean age
      of 32 years. The PAQ used in the AGAHLS during adolescence (13-16 years) and
      young adulthood (21-28 years) has the ability to measure the physical activity
      patterns of both genders, which are important for the development of bone mass at
      the adult age. MECHPA is more important than METPA. The highest coefficient of
      0.33 (p < 0.01) was between MECHPA measured over the total period of 15 years (13
      28 years) and lumbar BMD at age 32 years. Only during adolescence (12-16 years)
      was METPA more important with regard to lumbar BMD at age 32 years, with a beta
      of 0.21 (p < 0.01). The relative validity of the PAQ was established by comparing
      PAQ scores during four annual measurements in 200 boys and girls with two other
      objective measures of physical activity: movement counters (pedometers) and heart
      rate monitoring. These showed significant (p < 0.01) correlations in both
      genders, varying between 0.16 and 0.20. The small variation indicates, however,
      that all three instruments measure different aspects of physical activity. The
      results from the PAQ, with respect to MECHPA, validated in humans the results
      from animal studies in which bone adaptation during skeletal growth and
      development continuously adjust skeletal mass and architecture to changing
      mechanical stimuli caused by physical activity.

PMID- 11996925
TI  - Two new C-nor/D-homo corticosteroids formed by dehydration rearrangement of a
      12beta-hydroxy corticoid.
AB  - Two new C-nor/D-homo corticosteroids were isolated from the filtrate of the
      triene carbonate intermediate during the production of betamethasone. Their
      structures were elucidated based on NMR spectroscopic studies and mass spectral
      analyses. The mechanism of formation of each of these two steroids was postulated
      as a Wagner-Meerwein rearrangement of the corresponding 12beta-hydroxy steroid.
      The new 12beta-hydroxy corticosteroid was also isolated from the fermentation
      process of betamethasone synthesis. Its structure was identified via NMR and mass
      spectroscopic studies. Treatment of the new 12beta-hydroxy corticoid with PCl(5)
      at low temperature provided two C-nor/D-homo compounds in a ratio of 1:1.
      Conversion of 12beta-hydroxy corticoid into a corresponding 12beta-mesylate
      followed by heating in HOAc to 110 degrees C in the presence of NaOAc produced a
      mixture of the rearranged products in a 1:4 ratio.

PMID- 11996926
TI  - 3-Deoxy-1beta,20-dihydroxyecdysone from the leaves of Diploclisia glaucescens.
AB  - Chemical investigation of methanol extract of the leaves of Diploclisia
      glaucescens of the family Menispermaceae furnished a new ecdysteroid, 3-deoxy
      1beta,20-dihydroxyecdysone. The structure of the new ecdysteroid was established
      on detailed analysis of spectral data. The 3-deoxy ecdysteroid showed 40% potency
      of 20-hydroxyecdysone in the spiracle index assay using the fourth instar larvae
      of the silkworm Bombyx mori.

PMID- 11996927
TI  - Effects of androstenedione administration on epitestosterone metabolism in men.
AB  - Androstenedione is a steroid hormone sold over-the-counter to individuals who
      expect that it will enhance strength and athletic performance. Endogenous
      androstenedione is the immediate precursor of testosterone. To evaluate the
      metabolism of oral androstenedione, we randomly assigned 37 healthy men to
      receive 0 (group 1), 100 mg (group 2), or 300 mg (group 3) of androstenedione in
      a single daily dose for 7 days. Eight-hour urines were collected 1 day before the
      start of androstenedione, and on days 1 and 7. Using gas chromatography-mass
      spectrometry, we measured excretion rates of glucuronide-conjugated
      epitestosterone, its putative precursor (E-precursor), and metabolites (EM-1 and
      EM-2), and we evaluated possible markers of androstenedione administration. Day 1
      and 7 rates were not different: the means were averaged. The means (microg/h) for
      groups 1, 2, and 3, respectively were, for epitestosterone 2.27, 7.74, and 18.0;
      for E-precursor, 2.9, 2.0, and 1.5; for EM-1/E-precursor 0.31, 1.25, and 2.88;
      for EM-2/E-precursor 0.14, 0.15, and 1.15; for testosterone/epitestosterone (T/E)
      1.1, 3.5, and 3.2. Epitestosterone, EM-1, and EM-2 excretion was greater in
      groups 2 and 3 versus group 1 (0.0001 < P < 0.03), as were EM-1/E-precursor, EM
      2/E-precursor, and T/E. E-precursor excretion was lower in groups 2 (P = 0.08)
      and 3 (P = 0.047) versus group 1. Androstenedione increases excretion of
      epitestosterone and its two metabolites, while decreasing that of its precursor.
      Elevated ratios of EM-1- and EM-2/E-precursor, and the presence of 6alpha
      hydroxyandrostenedione are androstenedione administration markers.

PMID- 11996928
TI  - Evaluation of progesterone-ovalbumin conjugates with different length linkers in
      enzyme-linked immunosorbant assay and surface plasmon resonance-based
      immunoassay.
AB  - A series of progesterone-4-ovalbumin (OVA) conjugates with different length
      linkers (4-, 11-, and 18-atoms long) were synthesized by successive aminocaproic
      acid homologation of 3-(pregn-4-ene-3,20-dione-4-yl)thiopropanoic acid (1) before
      conjugation to ovalbumin. The performance studies of these progesterone-4
      ovalbumin conjugates showed that the effects of the length of linker on the
      antibody binding are dependent upon different immunoassay formats. In a rapid
      flow biosensor surface, on a BIAcore Surface Plasmon Resonance (SPR) instrument,
      antibody-binding capacities and response rate were dramatically increased for
      progesterone-4-ovalbumin conjugates when the length of the linker was incremented
      from 4 atoms to 11 or 18 atoms. Thus, highly sensitive SPR-based immunoassays for
      progesterone over a range of 0.1-50 ng ml(-1) were developed using biosensor
      surfaces immobilized with progesterone-ovalbumin conjugates having extended
      linkers. The SPR-based assays were fully competitive with conventional enzyme
      linked immunosorbant assay (ELISA) but much more rapid and simple. However, there
      were little changes in antibody-binding performance using a conventional ELISA
      for the same conjugates. The progesterone-4-ovalbumin conjugate (1-OVA) had
      better antibody binding than its progesterone-7alpha-ovalbumin analog (2-OVA) in
      the SPR-based assay, but with a conventional ELISA there was no significant
      difference between these two isomeric conjugates.

PMID- 11996929
TI  - Testosterone and estradiol differentially regulate TSH-induced thyrocyte
      proliferation in immature and adult rats.
AB  - Though sex steroids are found to influence thyroid pathogenesis in human and in
      animals, their role in normal thyroid growth and thyrocyte proliferation is not
      yet understood fully. The present study is addressed to know the effect of
      testosterone and estradiol on the basal and TSH-induced thyrocyte proliferation
      in immature and adult rats in vitro. The male and female Wistar rats were
      gonadectomized (GDX) and one group of GDX rats were supplemented with either
      testosterone or estradiol. After the experimental period, the rats were
      sacrificed by decapitation and thyroid glands were removed, washed in Hank's
      Balanced Salt Solution (HBSS), pH 7.4 and digested with the enzyme mixture
      containing 0.08% collagenase and 0.12% dispase in HBSS. The isolated follicles
      were washed thrice with Dulbecco's modified Eagle's medium (DMEM) containing 0.5%
      fetal bovine serum (FBS), and were cultured in Falcon's tissue culture flasks
      containing 5 ml DMEM with FBS (5%) transferrin (5 microg/ml), hydrocortisone (10(
      8) M), somatostatin (10 microg/ml), insulin (10 microg/ml) and glycyl-L-histidyl
      L-lysine acetate (10 microg/ml). The cells (2.5 x 10(4)) were exposed to various
      exponential doses of TSH or testosterone (6.25-800 ng/ml) or estradiol (6.25-800
      pg/ml). It is suggested from the present study that both TSH and sex steroids
      enhance thyrocyte proliferation. The mitogenic effect of TSH is greater than that
      of sex steroids. Sex steroids modulate TSH-induced cell proliferation in a gender
      specific manner.

PMID- 11996930
TI  - Synthesis of steroidal diacyl hydrazines and their 1,3,4-oxadiazole derivatives.
AB  - Homogeneous catalytic hydrazinocarbonylation of some steroid derivatives
      possessing iodo-alkenyl moiety (17-iodo-androst-16-ene 1, 17-iodo-3-methoxy-estra
      1,3,5(10),16-tetraene 2, 17-iodo-4-aza-4-methyl-androst-16-en-3-one 3 and 17-iodo
      6beta-hydroxy-3alpha,5alpha-cycloandrost-16-ene 4) were carried out in the
      presence of a palladium catalyst, a base and acetic or benzoic hydrazide as the
      nucleophilic reagent. The corresponding N-acetamido-carbamoyl 1a-4a or N
      benzamido-carbamoyl derivatives 1b-4b were obtained in high yields. Some of these
      derivatives served as starting materials for the synthesis of new steroidal 1,3,4
      oxadiazole compounds.

PMID- 11996931
TI  - Synthesis of [26-2H(3)]brassinosteroids.
AB  - A number of [26-2H(3)]brassinosteroids were prepared for biochemical studies. The
      parent, nondeuterated compounds were considered to be biosynthetic intermediates
      in brassinosteroid biosynthesis. Claisen rearrangement was used to construct the
      steroidal side chain. Deuterium was introduced by reducing the corresponding
      intermediates with lithium aluminium deuteride.

PMID- 11996932
TI  - [3,3]-Claisen rearrangements in 24alpha-methyl steroid synthesis. Application to
      campesterol, crinosterol, and Delta25-crinosterol side chain construction.
AB  - This paper elaborates an improved synthesis of crinosterol and campesterol
      starting from stigmasterol. The proposed approach is based on Claisen
      rearrangement of Delta23-22-allylic alcohols with various configurations of the
      22-hydroxy group and geometry of the Delta23-double bond. It allows complete use
      of the starting steroid for preparing 24alpha-methyl derivatives. It was possible
      to partially control the stereochemistry at C-25. Hydrogenation of the Delta22
      double bond was shown to proceed with partial isomerization of the C-24 alkyl
      substituent. The Ireland ester enolate variant of the Claisen rearrangement was
      demonstrated to be useful for preparing 24alpha-methyl steroids containing the
      Delta22,25-system.

PMID- 11996933
TI  - 19-Noraldosterone in pregnancy-induced hypertension.
AB  - Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal
      morbidity and mortality. 19-Noraldosterone, which was shown to be synthesized in
      the human adrenal gland, exhibits potent mineralocorticoid and hypertensive
      activity. To examine the role of mineralocorticoids in the pathophysiology of
      PIH, we studied urinary 19-noraldosterone, tetrahydroaldosterone, free cortisol,
      and cortisone concentrations and mineralocorticoid receptor levels in peripheral
      blood mononuclear leukocytes, from 17 women with PIH and 16 normal pregnant women
      as controls. Sequence analysis of the mineralocorticoid receptor gene in PIH
      patients was also done. The 24-h urinary excretion of 19-noraldosterone was
      significantly lower in PIH (120 +/- 38 pmol/day) than in controls (358 +/- 55
      pmol/day) (P < 0.05). Urinary tetrahydroaldosterone was also decreased in PIH
      compared with controls. Ratios of urinary free cortisol to cortisone (a measure
      of 11beta-hydroxysteroid dehydrogenase 2 activity) did not differ significantly
      between groups. Mineralocorticoid receptor density was significantly (P < 0.05)
      decreased in the PIH group (133 +/- 15 binding sites/cell) compared with controls
      (255 +/- 21 binding sites/cell). No mutations were found in the coding region of
      the mineralocorticoid receptor gene in PIH. These results suggest that
      circulating aldosterone, 19-noraldosterone, and renal 11beta-hydroxysteroid
      dehydrogenase2 do not contribute to the pathogenesis of PIH. Regulatory factors
      that cause the down-regulation of the mineralocorticoid receptor in PIH should be
      clarified.

PMID- 11996934
TI  - Synthesis and evaluation of the cardiovascular effects of two, membrane
      impermeant, macromolecular complexes of dextran-testosterone.
AB  - The incidence of cardiovascular disease is greater in men than in premenopausal
      women. Testosterone has been considered a significant risk factor for
      cardiovascular disease, but testosterone's mechanism of action and its cellular
      site of action are still not clear. However, it is likely that non-genomic
      extracellular effects of the hormone are involved. With the aim of providing
      further information about this phenomenon, two membrane impermeant,
      macromolecular complexes of testosterone were synthesized and their
      cardiovascular effects were evaluated. We covalently bound testosterone (through
      carbon 3 or C-17 functional groups) to dextran (2 MDa) and evaluated its effects
      on isolated and perfused rat hearts (Langerdorff model). Our results showed that
      the macromolecular complexes increased vascular resistance similarly to free
      testosterone and blocked adenosine-induced vasodilatation. These effects were
      exerted rapidly and possibly through a non-genomic mechanism. Blockade of C-3 or
      C-17 functional groups by binding to macromolecular dextran induced no
      qualitative and/or quantitative changes in testosterone-induced effects.

PMID- 11996935
TI  - 13C-NMR study of 4-azasteroids in solution and solid state.
AB  - A group of biologically active 4-azasteroids was studied by 13C-NMR spectroscopy
      in solution and in the solid phase. A full assignment of signals in the spectra
      of samples in chloroform was performed for thirteen 4-azasteroids using two
      dimensional techniques. Substituent and steric effects of a nitrogen atom, and
      their influence on chemical shifts of the neighboring carbon atoms are discussed.
      CP MAS spectra were obtained for five 4-azasteroids including finasteride. The
      spectra confirmed polymorphism of the latter compound. In addition to the
      polymorphic forms that are already known, a new molecular complex of finasteride
      with dioxane is reported.

PMID- 11996936
TI  - AUUUA motifs in the 3'UTR of human glucocorticoid receptor alpha and beta mRNA
      destabilize mRNA and decrease receptor protein expression.
AB  - An association between a gene polymorphism of the human glucocorticoid receptor
      (hGR) gene and rheumatoid arthritis has recently been suggested. This
      polymorphism contains an A to G mutation in the 3'UTR of exon 9beta, which
      encodes the 3'UTR of the mRNA of the hGRbeta isoform. The hGRbeta isoform can act
      as a dominant negative inhibitor of hGRalpha, and therefore may contribute to
      glucocorticoid resistance. The A to G mutation is located in an AUUUA motif,
      which is known to destabilize mRNA. In the present study, the importance of the
      mutation in this AUUUA motif was further characterized and mutations in other
      AUUUA motifs in the 3'UTR of hGRbeta and hGRalpha mRNA were studied. hGRbeta and
      hGRalpha expression vectors, carrying mutations in one AUUUA motif or all AUUUA
      motifs were transiently transfected into COS-1 cells. Each transfected vector was
      analyzed for the mRNA expression level, the mRNA turnover rate and the protein
      expression level. The naturally occurring mutation in the 3'UTR of hGRbeta mRNA
      increased mRNA stability and protein expression. Mutation of two other AUUUA
      motifs in the 3'UTR of hGRbeta, or mutation of all four AUUUA motifs resulted in
      a similar effect. Mutation of the most 5' AUUUA motif did not alter hGRbeta mRNA
      expression or mRNA stability. Mutation of all 10 AUUUA motifs in the 3'UTR of
      hGRalpha mRNA increased hGRalpha mRNA expression and mRNA stability as well as
      expression of the receptor protein level. Thus, the naturally occurring mutation
      in an AUUUA motif in the 3'UTR of hGRbeta mRNA results not only in increased mRNA
      stability, but also in increased receptor protein expression, which may
      contribute to glucocorticoid resistance. A similar role is suggested for two
      other AUUUA motifs in the 3'UTR of hGRbeta mRNA and for the 10 AUUUA motifs that
      are present in the 3'UTR of hGRalpha.

PMID- 11996937
TI  - Intravenous injection of human sex steroid hormone-binding globulin in mouse
      decreases blood clearance rate and testicular accumulation of orally administered
      [2-125I]iodobisphenol A.
AB  - Bisphenol A, an environmental compound with estrogenic activity, has been shown
      to bind human sex steroid hormone-binding globulin (hSHBG), the main plasma
      transport protein which regulates the metabolism of androgens and estrogens and
      limits their access to target organs. The present study was conducted to
      determine whether physiologically relevant concentrations of hSHBG can influence
      the blood clearance rate of bisphenol A and its accumulation in the testes. A
      radioactive [2-125I]iodobisphenol tracer was synthesized with an association
      constant (Ka) for binding to hSHBG of 0.14 +/- 0.01 x 10(6) M(-1) at 37 degrees
      C, a value much lower than for [2-125I]iodoestradiol, which was also synthesized.
      We used i.v. injection of immunopurified hSHBG in adult male mice to maintain
      hSHBG levels within the physiologically possible range for humans (27-267 nM)
      before gavage administration of [2-125I]iodobisphenol or [2-125I]iodoestradiol,
      for measuring the blood clearance rate of radioactive signal in blood samples
      taken during the following 120 min. Testicular accumulation of radioactivity was
      measured 24 h and 48 h after gavage of [2-125]iodobisphenol A. In mice receiving
      immunopurified hSHBG or vehicle, the time-dependent blood clearance of
      radioactivity exhibited a bi-exponential decrease which indicated alpha-diffusion
      and beta-elimination phases for both radioactive ligands. The presence of
      circulating hSHBG significantly and dose-dependently lowered the clearance rate
      of radioactivity. However, much higher circulating levels of hSHBG were required
      to retard the blood clearance of [2-125I]iodobisphenol A as compared to those
      required for [2-125I]iodoestradiol, in keeping with the important difference in
      their respective Ka value for binding to SHBG. In addition, mice treated with
      hSHBG exhibited significantly (P = 0.036) reduced testicular accumulation of
      radioactivity 24 h and 48 h after ingestion of [2-125I]iodobisphenol A. Provided
      that the binding properties of bisphenol A for hSHBG are not substantially
      different from those measured for [2-125I]iodobisphenol A, these findings suggest
      that, although hSHBG binds 2-mono-iodobisphenol A with a relatively low binding
      affinity, high enough concentrations of circulating hSHBG (range concentrations
      between 85 and 267 nM) are potentially able to exert a protective effect against
      exposure to bisphenol A.

PMID- 11996938
TI  - B cells express intracellular but not surface receptors for testosterone and
      estradiol.
AB  - Increasing evidence indicates the existence of membrane receptors for
      testosterone (mAR) and estradiol (mER) on the surface of cells, besides the
      classic intracellular androgen receptor (iAR) and estrogen receptors (iER). Here,
      we investigate the occurrence of sex steroid receptors in B cells isolated from
      the spleen of C57BL/10 mice using magnetic cell sorting. RT-PCR reveals the
      presence of iAR, iERalpha, but not iERbeta. Using different anti-iAR and anti-iER
      antibodies flow cytometry and confocal laser scanning microscopy (CLSM) localize
      iAR and iERalpha in the cytoplasm, which are translocatable to the nucleus upon
      incubation with testosterone (T) and 17beta-estradiol (E(2)). The surface of B
      cells is devoid of iAR and iERalpha and does not bind any T and E(2) conjugated
      to BSA-FITC as revealed by flow cytometry and CLSM. In accordance, T and E(2) are
      not able to induce any rapid rise in in the intracellular free Ca2+ concentration
      of Fura-2 loaded B cells. Our data indicate that B cells express neither mAR nor
      mER on their surfaces, in contrast to other major cells of the immune system such
      as T cells and macrophages.

PMID- 11996939
TI  - Regulation of estrogen activity in human endometrium: effect of IL-1beta on
      steroid sulfatase activity in human endometrial stromal cells.
AB  - We investigated the effect of interleukin 1beta (IL-1beta) on steroid sulfatase
      (STS) activity and the expression of STS mRNA in human endometrial stromal cells.
      Endometrial tissue samples were obtained from patients undergoing hysterectomy to
      remove uterine fibroids. Stromal cells were isolated from the tissue preparation
      and cultured. IL-lbeta (1 approximately 100 ng/ml) was added into the culture
      medium and incubated for 24 h. The expression of STS mRNA was measured by
      competitive RT-PCR. The addition of IL-lbeta at 10 and 100 ng/ml suppressed STS
      mRNA expression to 55.2 +/- 12.8% and 25.1 +/- 10.9%, respectively, of the
      control sample to which no IL-lbeta had been added. STS activity was measured by
      radiolabelled steroid metabolite using thin layer chromatography, and this
      activity was also significantly suppressed in response to the administration of
      IL-lbeta in a dose-dependent manner. When IL-1 receptor antagonist (IL-1ra) was
      added together with IL-1beta to the culture medium, mRNA expression and STS
      activity were recovered. The present study is the first to demonstrate IL-1beta
      regulation of STS activity locally in human endometrium. IL-1beta suppressed mRNA
      and activity of STS in stromal cell culture. This initial demonstration of IL
      1beta regulation of STS implies that IL-1beta may control the steroid
      microenvironment in human uterine endometrium by reducing biologic action of
      estrogen.

PMID- 11996940
TI  - CH(3)ReO(3)-catalyzed oxidation of cholesta-5,7-dien-3beta-yl acetate with the
      urea-hydrogen peroxide adduct under various conditions. Synthesis of the natural
      epoxy sterol 9alpha,11alpha-epoxy-5alpha-cholest-7-en-3beta,5,6beta-triol.
AB  - This article describes the oxidation of cholesta-5,7-dien-3beta-yl acetate (4)
      with the urea-hydrogen peroxide adduct (UHP) using methyltrioxorhenium (MTO) as
      catalyst, under various conditions. Specifically, the effects of using different
      solvents (CHCl(3) and ethers) and additives (EtOH and pyridine) on the course of
      the MTO-catalyzed oxidation of 4 were investigated. Some new steroids (6, 9, 10
      and 11), obtained from this oxidation, were isolated and characterized on the
      basis of chemical evidence and interpretation of spectroscopic data including H-H
      COSY and HMBC experiments. The optimal solvent for the oxidation of 4 with
      MTO/UHP oxidizing system was diethyl ether. In this solvent the reaction is clean
      and gave as the main product 5,6beta-dihydroxy-5alpha-cholest-7-en-3beta-yl
      acetate (8, 65% yield), obtained with a more simple procedure and with a higher
      yield than that reported in literature. Sterol 8 is a key intermediate compound
      in the synthesis of many steroids of marine origin, biologically active,
      oxygenated at the B/C rings. In fact, starting from diol 8, we performed the
      synthesis of the natural cytotoxic epoxy sterol 9alpha,11alpha-epoxy-5alpha
      cholest-7-en-3beta,5,6beta-triol (15, 21% yield) with an improvement in yield and
      number of steps over a synthesis of the same natural product previously reported.
      When the oxidation of 4 with the MTO/UHP system in diethyl ether was performed in
      the presence of pyridine as ligand, the unsaturated epoxide 5,6alpha-epoxy-5alpha
      cholest-7-en-3beta-yl acetate (10, 90% yield) was obtained after only 5 min in
      good yield. In fact, pyridine, besides having beneficial effect on the reaction
      rate, shuts down the ring opening reactions, as reported in literature.

PMID- 11996941
TI  - Synthesis and receptor-binding examination of 16-hydroxymethyl-3,17-estradiol
      stereoisomers.
AB  - The four 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers were
      synthesized and tested in a radioligand-binding assay. The estrogen receptor
      recognizes these compounds, but their relative binding affinities are lower than
      2.0% relative to that of the reference molecule estra-1,3,5(10)-triene-3,17beta
      diol. The affinities of the tested compounds for the androgen and progesterone
      receptors are very low (K(i)> 100 microm and 1 microM, respectively). The
      prepared 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers are therefore
      estrogen receptor-selective molecules.

PMID- 11996942
TI  - Apolipoprotein B metabolism in humans: studies with stable isotope-labeled amino
      acid precursors.
AB  - This article reviews the literature from 1986 to early 2001 relating to apoB100
      and apoB48 kinetics in humans using amino acid precursors labeled with stable
      isotopes. The following subjects are reviewed: (1) methodology; (2) normal
      individuals and the effects of aging; (3) diet; (4) hereditary dyslipidemias:
      familial hypercholesterolemia, familial combined hyperlipidemia, cholesteryl
      ester storage disease, cholesteryl ester transfer protein deficiency, lipoprotein
      lipase deficiency, familial hypobetalipoproteinemia, and truncated forms of apoB;
      (5) hormonal perturbations: estrogen, insulin, diabetes, obesity, and growth
      hormone; (6) the nephrotic syndrome; and (7) the effects of the statin class of
      drugs. Because of the advances which have been made in mass spectrometry
      techniques, the advantages of using non-radioactive tracers in humans have made
      stable isotope kinetic studies the present day standard in this area of research.

PMID- 11996943
TI  - Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in
      combined (mixed) hyperlipidemia.
AB  - C-reactive protein (CRP) is a non-specific but sensitive marker of underlying
      systemic inflammation. High CRP plasma levels correlate with risk for future
      cardiovascular events. The present study evaluated the effects of atorvastatin
      (10-40 mg) and bezafibrate (400 mg) on CRP concentrations after 6 and 12 months
      of treatment in 103 patients with combined (mixed) hyperlipidemia. The number of
      cardiovascular risk factors present in a given patient was associated with
      baseline CRP levels. After 6 months and 1 year, atorvastatin treatment was
      associated with significant (P<0.001) decreases from baseline of CRP
      concentrations by 29 and 43%, respectively, while bezafibrate-treated patients
      showed non-significant reductions of 2.3 and 14.6%, respectively (P=0.056 and
      0.005 for the respective differences between the two treatment arms at 6 months
      and 1 year). The magnitude of change in CRP after 1 year was directly related to
      baseline CRP levels. Covariance analysis showed that CRP decreases in the
      atorvastatin group were unrelated to total cholesterol and LDL cholesterol
      reductions; however, they were directly related to triglyceride changes (r=0.28,
      P=0.047) and inversely related to HDL cholesterol changes (r=-0.28, P=0.045). A
      model including baseline CRP values and treatment effect showed that atorvastatin
      use was a significant predictor of change in CRP levels over time (beta=0.82,
      P=0.023). These results suggest a potential anti-atherosclerotic additional
      benefit of atorvastatin in patients at a risk of cardiovascular disease.

PMID- 11996944
TI  - Chlamydial infection in canine atherosclerotic lesions.
AB  - We attempted to detect chlamydial antigens in canine atherosclerotic lesions from
      seven dogs by immunohistochemical technique using anti-Chlamydia psittaci (C.
      psittaci) polyclonal and anti-C. pneumoniae monoclonal antibodies. Immunopositive
      signals to both antibodies were recognized in the atherosclerotic lesions of the
      aortas, coronary and splenic arteries of all dogs. Positive signals were found in
      the foamy cytoplasm of infiltrated macrophages and extracellular matrices in the
      lesions. In some lesions, cytoplasm of the endothelial cells and smooth muscle
      cells was also immunopositive against both antibodies. By electron microscopy,
      chlamydial microorganisms were found in the cytoplasm of endothelial cells and
      smooth muscle cells. Using polymerase chain reaction (PCR), detection of C.
      pneumoniae DNAs were performed in the spleen, heart (coronary arteries) and
      kidney in one of the seven dogs. Positive 314 bp PCR products were obtained in
      all samples of the dog. These results confirmed the presence of viable Chlamydiae
      in atheromas and supported the conclusion that the organism may be an active
      factor in the pathogenesis of canine, as well as human atherosclerosis.

PMID- 11996945
TI  - Angiotensin II stimulates synthesis of vascular smooth muscle cell proteoglycans
      with enhanced low density lipoprotein binding properties.
AB  - One mechanism by which Angiotensin II (AII) may promote atherogenesis is through
      modulation of proteoglycan (PG) metabolism by vascular smooth muscle cells (SMC).
      To test this hypothesis, we investigated the effect of AII on PG synthesis by
      human aortic SMC and the ability of the newly synthesized PG to bind low density
      lipoprotein (LDL). AII stimulated PG synthesis by SMC in a dose- and time
      dependent manner. In the presence of 1 microM AII, medium and cellular PG
      increased by 73 and 97%, respectively. AII caused a 55% increase in biglycan mRNA
      which resulted in a 52% increase in biglycan synthesis. Losartan, an AII receptor
      antagonist, and broad and isoform-specific protein kinase C (PKC) inhibitors
      abolished the AII-induced up-regulation of PG synthesis. Moreover, direct
      activation of PKC with phorbol ester stimulated PG synthesis significantly.
      Similarly, inhibitors of tyrosine kinase also caused inhibition of PG synthesis.
      AII increased the size and charge density of the newly synthesized PG. In
      addition, AII stimulated the synthesis of PG that bound LDL with very high
      affinity by 2.5-fold to 3-fold over control. These results suggest that the AII
      mediated alterations in vascular SMC PG metabolism may contribute to the
      pathophysiology of atherosclerosis.

PMID- 11996946
TI  - Determinants of HDL particle size in patients with the null (P207L) or defective
      (D9N) mutation in the lipoprotein lipase gene: the Quebec LipD Study.
AB  - The aim of the present study was to examine the impact of the defective D9N and
      the null P207L mutations in the lipoprotein lipase (LPL) gene on high density
      lipoprotein (HDL) particle size in relation to specific environmental factors
      such as obesity, gender and menopausal status. Analyses were carried out in 118
      heterozygous carriers of the D9N mutation and 88 heterozygous for the P207L
      mutation. HDL particle size was measured on whole plasma by non-denaturing 4-30%
      polyacrylamide gradient gel electrophoresis. Although carriers of the P207L
      mutation presented a more deteriorated lipoprotein-lipid profile compared with
      carriers of the D9N mutation, there was no difference in HDL particle size
      between the P207L and D9N carriers (81.9+/-4.5 vs. 82.7+/-4.4 A, respectively,
      P=0.2). Multivariate analyses indicated that waist circumference (P=0.001) and
      HDL cholesterol levels (P<0.001) were independent predictors of HDL particle size
      among carriers of the defective D9N mutation. On the other hand, gender (P=0.03),
      plasma cholesterol (P=0.01) and TG (P=0.04) levels were significant predictors of
      HDL particle size among carriers of the null P207L mutation in multivariate
      analyses. These results suggest that the nature of the mutation in the LPL gene
      modifies the relationship of HDL particle size to other metabolic variables and
      secondary factors such as abdominal obesity and gender.

PMID- 11996947
TI  - High glucose induced nuclear factor kappa B mediated inhibition of endothelial
      cell migration.
AB  - Delayed wound healing and accelerated atherosclerosis are common vascular
      complications of diabetes mellitus. Although elevated blood glucose level is the
      major contributing factor, mechanisms that mediate these complications are not
      clearly understood. In the present study, we have demonstrated that elevated
      glucose inhibits endothelial cell migration, thereby delaying wound healing. Our
      results clearly indicated that high glucose (10 or 30 mM) induced activation of
      nuclear factor kappa B (NF-kappaB) inhibited endothelial cell migration (P<0.05).
      High glucose induced NF-kappaB DNA binding activity may mediate this inhibition
      of migration by regulating intracellular nitric oxide. In vitro wound healing
      model in human aortic endothelial cells (HAEC) were used to evaluate cell
      migration under the influence of high glucose. The migration inhibited by high
      glucose was restored by NF-kappaB inhibitors (including E3-4-methylphenyl
      sulfonyl-2-propenenitrile, N-tosyl-Lys-chloromethylketone (TLCK), or over
      expression of inhibitor subunit of kappaB) and endothelial nitric oxide synthase
      inhibitors (N-methyl-L-arginine (L-NMMA); and Nomega-nitro-L-arginine methyl
      ester (L-NAME)). Furthermore, NF-kappaB inhibitors attenuated high glucose
      induced eNOS expression and intracellular nitric oxide (NO) production.
      Cytoskeletal immunofluorescence staining confirmed differences in actin
      distribution in HAEC incubated in high glucose in the presence or absence of NF
      kappaB and NO inhibitors, explaining the differences observed in migration. In
      summary, our results for the first time suggest therapeutic strategies involving
      inhibition of NF-kappaB activation induced by high glucose, which may improve
      wound healing and help avoid some of the vascular complications of diabetes.

PMID- 11996948
TI  - Collagen suppresses the proliferative phenotype of allylamine-injured vascular
      smooth muscle cells.
AB  - Repeated cycles of oxidative injury by allylamine induce proliferative rat
      vascular smooth muscle cell (vSMC) phenotypes characterized by enhanced secretion
      of osteopontin (OPN). The present study was designed to evaluate the role of
      extracellular matrix (ECM) interactions in the induction of proliferative
      phenotypes in this model of oxidant injury. Because OPN is involved in
      ECM/integrin signaling, and may participate in proliferative control, the
      proliferation profiles of control and allylamine vSMCs seeded on different
      matrices were compared. Allylamine cells exhibited a proliferative advantage over
      controls when seeded on plastic, Pronectin, or fibronectin, but not type I
      collagen. Addition of GRGDS peptide selectively enhanced [3H]-thymidine
      incorporation in allylamine vSMCs, while anti-OPN antibodies nullified their
      proliferative advantage. Allylamine cells exhibited altered expression of alpha1,
      alpha5 and beta3 integrin subunits and enhanced downstream integrin-coupled
      increases in focal adhesion kinase, AP-1 and NF-kappaB binding activity.
      Inhibition of NF-kappaB by pyrrolidine dithiocarbamate selectively compromised
      proliferation of allylamine vSMCs, while seeding on a non-permissive collagen
      matrix ablated enhancement of NF-kappaB inducibility. These results implicate ECM
      interactions in the deregulation of vSMC proliferation following repeated cycles
      of oxidative chemical injury.

PMID- 11996949
TI  - Pravastatin sodium, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, decreases serum total cholesterol in Japanese White rabbits by two
      different mechanisms.
AB  - Pravastatin sodium (pravastatin), an inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMG-CoA reductase), when orally administered to male
      Japanese White (JW) rabbits at 1-30 mg/kg for 21 days, decreased the
      concentrations of total cholesterol, low density lipoprotein (LDL)-cholesterol
      and high density lipoprotein (HDL)-cholesterol in a dose-dependent manner. On the
      other hand, pravastatin did not change the concentration of serum triglycerides
      and very low density lipoprotein (VLDL)-cholesterol. On day 21, LDL-cholesterol
      was significantly decreased at doses higher than 3 mg/kg, whereas HDL-cholesterol
      was significantly reduced at doses higher than 10 mg/kg. The concentrations of
      hepatic LDL receptor proteins determined by immunoblot analysis increased at the
      same dose at which the concentrations of LDL-cholesterol decreased. The serum
      concentrations of HDL-cholesterol were decreased at the same dose at which VLDL
      cholesterol secretion rates from the liver were reduced. The present study
      suggests that in JW rabbits, pravastatin decreases the serum concentration of LDL
      cholesterol through an LDL receptor pathway, whereas the agent lowers the
      concentration of HDL-cholesterol by the mechanisms associated with a reduction of
      VLDL-cholesterol secretion from the liver.

PMID- 11996950
TI  - beta-very low density lipoprotein enhances inducible nitric oxide synthase
      expression in cytokine-stimulated vascular smooth muscle cells.
AB  - beta-very low-density lipoprotein (beta-VLDL), a collective term for VLDL and
      chylomicron remnants, has recently shown to potently promote the development of
      atherosclerosis. However, the effects of beta-VLDL on the accumulation of nitric
      oxide (NO) and the expression of inducible NO synthase (iNOS) in vascular smooth
      muscle cells (VSMC) have not been determined. In this study, we measured the
      accumulation of nitrite, stable metabolite of NO and examined the expression of
      iNOS protein and mRNA using Western blotting and RT-PCR, respectively, in VSMC.
      NF-kappaB activation in VSMC was examined by gel retardation assay. Incubation of
      cell cultures with interleukin-1beta (IL-1beta) for 24 h caused a significant
      increase in nitrite accumulation. Although beta-VLDL alone did not increase
      nitrite accumulation in unstimulated VSMC, beta-VLDL significantly enhanced
      nitrite accumulation in IL-1beta-stimulated VSMC in a time- and dose-dependent
      manner. beta-VLDL-induced nitrite accumulation in IL-1beta-stimulated VSMC was
      accompanied by an increase in iNOS protein and mRNA expression. In addition, IL
      1beta induced NF-kappaB activation in VSMC, an effect that was increased by the
      addition of beta-VLDL. Use of specific tyrosine kinase inhibitor herbimycin A,
      genistein, or PP2 (Src family kinase inhibitor) indicated that tyrosine kinases
      are required for IL-1beta-stimulated and beta-VLDL-enhanced nitrite accumulation,
      while specific inhibition of ERK1/2 or p38-MAP kinase had no effects. Our results
      suggest that beta-VLDL enhances iNOS expression and nitrite accumulation in IL
      1beta-stimulated VSMC through tyrosine kinase(s)-dependent mechanisms.

PMID- 11996951
TI  - Atherosclerotic lesions in genetically modified mice quantified in vivo by non
      invasive high-resolution magnetic resonance microscopy.
AB  - We have previously shown that magnetic resonance microscopy (MRM) accurately
      quantifies atherosclerosis in Apolipoprotein E deficient (ApoE(-/-)) mice aged 36
      84 weeks. The present study tests MRM in the quantification of aortic
      atherosclerosis over a broader range of lesion severity. Younger mice with less
      advanced disease were imaged in order to evaluate sensitivity, specificity and
      maximum practical resolution of MRM. Nineteen mice underwent in vivo MRM. Wall
      area measurements by MRM and light microscopy (LM) (n=43) were highly correlated
      (r=0.85, slope=0.88, P<0.0001). Wall areas by MRM ranged from 0.114 to 0.934
      (median, 0.334) mm(2). A threshold of 0.35 mm(2), for the upper limit of normal,
      gave MRM positive predictive value (PPV) for detecting abnormally thickened
      arteries=89.5% and negative predictive value (NPV)=75%, referred to LM. Lesion
      shape assessed by LM and MRM were also well correlated (r=0.72, P<0.001).
      Increased wall area in atherosclerosis was found by MRM (P=0.01) and LM
      (P<0.0001) to be accommodated entirely by 'positive remodeling', confirming the
      importance of determining plaque size directly. MRM accurately quantifies mouse
      aortic atherosclerosis and will enhance studies in this important animal model.

PMID- 11996952
TI  - Large scale isolation of non-uniform shear stress-responsive genes from cultured
      human endothelial cells through the preparation of a subtracted cDNA library.
AB  - To investigate the molecular mechanisms responsible for the regional selectivity
      of early atherogenesis, we have applied a non-uniform shear stress to cultured
      human umbilical vein endothelial cells (HUVEC). We used a microcarrier culture
      system and a combination of subtraction and reverse-subtraction methods to
      isolate a number of genes upregulated by shear stress. The resultant subtracted
      library includes several known genes (e.g. MCP-1, TM) whose responsiveness to
      shear stress has been previously reported, indicating that the library is
      enriched for genes upregulated by shear stress. Also included are atherosclerosis
      related genes (e.g. CTGF, IL-8) whose responsiveness to shear stress had not been
      demonstrated, other known genes whose relationship to atherosclerosis had not
      been reported, and novel genes. Some responsive to centrifugal force and shear
      stress (RECS) genes are also upregulated following stimulation by steady laminar
      shear stress in a parallel plate chamber. Interestingly, the library includes ET
      1 and PAI, which are well known atherogenic factors that are downregulated by
      laminar shear stress. This implies that turbulent shear stress has effects on
      HUVEC that are different from those elicited by laminar shear stress.
      Importantly, analysis of specimens taken from human aorta showed that several
      RECS genes are transcriptionally upregulated in atherosclerotic lesions,
      suggesting that the subtracted library includes novel therapeutic targets for the
      treatment of atherosclerosis.

PMID- 11996953
TI  - Sunflower, virgin-olive and fish oils differentially affect the progression of
      aortic lesions in rabbits with experimental atherosclerosis.
AB  - In this study we report the effects of sunflower, virgin olive and fish oils on
      the progression of aortic lesions. A total of 24 male New Zealand rabbits (six
      per each group) were fed for 50 days on a diet containing 3% lard and 1.3%
      cholesterol, to induce atherosclerosis. An atherogenic control group (A) was
      killed after this period and three groups were fed for an additional period of 30
      days with a diet composed of (1.75 g of supplemented oil and 98.25 of standard
      chow): sunflower oil (S), virgin olive oil (O) and fish oil (F). A control group
      (n=6) was fed with a standard chow diet for 80 days. LDL lipid composition and
      histological analysis of aortic atherosclerotic lesions were assayed. The
      atherogenic diet caused a significant increase of cholesterol levels in LDL and
      aorta tissue. Cholesterol ester content rose significantly in the aortic arch of
      groups S, O and F. Fatty streaks were found in all aortic sections, although only
      group S showed a significant progression of the lesion compared with group A. We
      conclude that the replacement of a high cholesterol-saturated fat diet by another
      cholesterol free-unsaturated fat diet does not regress atherosclerosis in rabbit.
      However, sunflower oil provokes a significant progression in lesion development,
      whereas diet enrichment with extra virgin olive oil and, to a lesser extent, fish
      oil, stops this progression.

PMID- 11996954
TI  - Cell replication induces in-stent lesion growth in rabbit carotid artery with
      preexisting intimal hyperplasia.
AB  - This study examined the responses of rabbit carotid artery with a preexisting
      intimal lesion, to stent implantation and balloon dilation. Rabbit carotid
      arteries were injured with a Fogarty catheter, and 28 days later the same
      arteries were subjected to implantation of a Palmaz-Schatz stent or balloon
      dilation angioplasty. Intimal size was significantly increased after stent
      implantation and balloon dilation, and no significant difference was detected
      between the two procedures. After stent implantation, replicating intimal cells
      were increased mainly in the inner intima, and the increase of cell replication
      was prolonged until day 28. In contrast, a significant increase of intimal cell
      replication was detected only at 2 days after balloon dilation. Intimal cell
      number after stent implantation was significantly higher than that after balloon
      dilation from day 7. Abundant leukocytes adhered to the luminal surface until 14
      days after stent implantation, and significant infiltration of macrophages was
      observed in the mid-intima. Activation of proteases was prolonged, and obvious
      accumulation of proteoglycans was detected after stent implantation as compared
      with balloon dilation. These findings suggest that, an increase in cell
      replication is critical in the development of in-stent restenosis, and that
      inflammatory responses represent a unique property after stent implantation.

PMID- 11996955
TI  - Distinct mechanisms implicated in atherosclerosis-induced erectile dysfunction in
      rabbits.
AB  - Ageing and atherosclerosis (ATH) are well-known risk factors for erectile
      dysfunction (ED). To identify the mechanisms implicated in ATH-induced ED,
      independently of its ageing-associated component, we studied (i) erectile
      responses in vivo, and, (ii) endothelium-dependent and independent relaxations of
      corporal strips from young adult (YAD, n=6), adult (AD, n=6), and cholesterol-fed
      (ATH, n=8) New-Zealand white rabbits. Measurement of Intima/Media (I/M) ratio on
      iliac arteries from ATH rabbits determined those with moderate (Mod ATH, 0.5+/
      0.3) or severe (Sev ATH, 1.5+/-0.4, P<0.05 Mann-Whitney) atherosclerotic lesions.
      Erectile responses were reduced in AD compared with YAD rabbits (at 6 V to 10 Hz:
      51.6+/-4.6% vs. 57.5+/-1.4%); they were similar in AD and mod ATH rabbits (48.1+/
      4.6%) but drastically impaired in Sev ATH rabbits (34.8+/-5.4%, P<0.05, two-way
      analysis of variance (ANOVA)). Corporal endothelium-dependent and -independent
      relaxations were comparable in YAD and AD rabbits (maximal relaxation to
      acetylcholine: 51.3+/-9.5 vs. 56.1+/-9.3%) but decreased in ATH rabbits (37.1+/
      1.6%, P<0.001, two-way ANOVA). These results suggest that the mechanisms
      implicated in ATH-induced ED are distinct from the ageing-related process in
      rabbits. Thus, future therapeutic targets to treat or prevent ATH-induced ED may
      include the reduction of the atherosclerotic plaque size or progression, as well
      as an improvement of the smooth muscle and endothelial reactivity of the corpus
      cavernosum.

PMID- 11996956
TI  - A 16-week fenofibrate treatment increases LDL particle size in type IIA
      dyslipidemic patients.
AB  - OBJECTIVE: The objective of the present study was to compare the effects of a 16
      week pharmacotherapy with fenofibrate (200 mg) or pravastatin (initially 20 mg
      for 8-weeks and, if necessary, increased to 40 mg) on low density lipoprotein
      (LDL) particle size assessed by gradient gel electrophoresis among patients with
      type IIa dyslipidemia. METHODS: For that purpose, type IIa dyslipidemic patients
      (cholesterol, 7.45+/-1.18 (S.D.) mmol/l; LDL cholesterol, 5.57+/-1.16 mmol/l;
      triglycerides (TGs), 1.66+/-0.43 mmol/l) were randomized to either fenofibrate
      (n=36) or pravastatin (n=43) therapy for 16 weeks. Fasting plasma lipoprotein
      levels as well as the LDL peak particle size (using 2-16% polyacrylamide gel
      electrophoresis) were assessed at baseline and after the 16-week treatment
      period. RESULTS: Whereas significant improvements in the plasma lipoprotein-lipid
      variables were observed with both fenofibrate and pravastatin treatments, LDL
      peak particle size was only significantly increased with fenofibrate therapy
      (+2.11+/-5.18 A, P<0.05). Among patients under fenofibrate therapy, changes in TG
      levels were negatively associated with changes in LDL peak particle size (r=
      0.54, P<0.0007), whereas no such association was found in pravastatin-treated
      patients. The prevalence of patients with small, dense LDL particles (as defined
      by LDL particle diameter <255.5 A) was reduced from 69.4 to 30.6% (P<0.05) among
      fenofibrate-treated patients as opposed to 81.4 to 72.1% (NS) in patients who
      received pravastatin. CONCLUSION: As pravastatin treatment had no effect on LDL
      size, it is suggested that the additional effect of fenofibrate therapy on LDL
      size may contribute to reduce the risk of coronary heart disease (CHD) beyond
      what can be expected from the reduction in LDL cholesterol concentration in type
      IIa dyslipidemic patients.

PMID- 11996957
TI  - A randomized, double-blind trial comparing the efficacy and safety of
      pitavastatin versus pravastatin in patients with primary hypercholesterolemia.
AB  - Pitavastatin (p-INN) is a novel and fully synthetic 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, with a cholesterol-lowering action
      stronger than that of other statins currently in use. A 12-week, multi-center,
      randomized, double-blind, controlled study was conducted to confirm the efficacy
      and safety of pitavastatin compared with pravastatin, an agent for using to
      reduce low density lipoprotein cholesterol (LDL-C) in hypercholesterolemic
      patients. Patients were recruited at 43 institutes in Japan. Following more than
      4 weeks run-in period, 240 patients were randomized to receive 2 mg of
      pitavastatin or 10 mg of pravastatin daily. At 12 weeks post-randomization, the
      pitavastatin group showed significantly lower LDL-C levels by -37.6% from
      baseline compared with -18.4% in the pravastatin group (P<0.05). Pitavastatin
      also significantly lowered total cholesterol (TC) by -28.2% compared with -14.0%
      of pravastatin (P<0.05). The LDL-C target level of <140 mg/dl was attained in 75%
      of the patients treated with pitavastatin, compared with 36% of those in the
      pravastatin group (P<0.05). Pitavastatin also significantly reduced triglycerides
      (TG), apo B, C-II and C-III, compared with pravastatin, and increased HDL-C, apo
      A-I and A-II, to the same extent of pravastatin. Safety was assessed by
      monitoring adverse events and measuring clinical laboratory parameters. The
      adverse event profile was similar for both treatment groups and neither treatment
      caused clinically relevant laboratory abnormalities. These results indicated that
      pitavastatin was more effective than pravastatin, and both drugs were well
      tolerated in the treatment of hypercholesterolemia.

PMID- 11996958
TI  - Coronary artery disease is associated with the ratio of apolipoprotein A-I/B and
      serum concentration of apolipoprotein B, but not with paraoxonase enzyme activity
      in Iranian subjects.
AB  - To determine the association of serum apolipoprotein (apo) A-I and B
      concentrations, and paraoxonase (PON) high-density lipoprotein (HDL) associated
      enzyme activity with angiographically determined coronary artery disease (CAD) in
      Iranian diabetic and non-diabetic CAD patients and non-diabetic control subjects,
      251 subjects aged 30-70 years, who underwent their first coronary angiography
      were matched and randomly assigned into three groups: CAD(+)DM(+), CAD(+)DM(-),
      and CAD(-)DM(-) (control). Stenosis of > or =50% in one or more coronary arteries
      was classified as CAD(+). CAD(-) was defined as a maximum stenosis of 10% in any
      coronary artery. Fasting serum concentrations of cholesterol (TC), triglycerides
      (TGs), LDL-C, HDL-C, apo A-I/B and PON activity were determined. Apolipoprotein
      concentrations were measured in a fasting serum sample by immunoturbidometric
      assay and paraoxonase/arylesterase activities by spectrophotometric assay of p
      nitrophenol/phenol production following addition of paraoxon/phenylacetate.
      Information concerning non-lipid risk factors were collected by questionnaires.
      No significant difference was observed in HDL-C, LDL-C, apo A-I, and
      PON/arylesterase activity between the study groups. The values of TC (213+/-38 vs
      196+/-45, P<0.05), TGs (209+/-187 vs 151+/-113, P<0.01), apo B (99+/-22 vs 96+/
      24, P<0.0001), TC/HDL-C (4.8+/-1.5 vs 4.0+/-1.3, P<0.001) and LDL-C/HDL-C (2.9+/
      1.1 vs 2.4+/-1.1, P<0.05) were higher and apo A-I/B (1.7+/-0.4 vs 2.0+/-0.6,
      P<0.01) was lower in CAD(+)DM(+) patients than in control subjects. In CAD(+)DM(
      ) group, only the level of apo B (96+/-24 vs 85+/-18, P<0.01), and the ratio of
      apo A-I/B (1.8+/-0.4 vs 2.0+/-0.6, P<0.01), were significantly higher than those
      of control group. On multiple logistic regression analysis, the best markers for
      discrimination between CAD(+) groups and CAD(-) control subjects were the ratio
      of apo A-I/B in diabetic and apo B in non-diabetic patients. The results suggest
      that in Iranian diabetic and non-diabetic patients with CAD the concentration of
      apolipoproteins are better markers than traditional lipid parameters in
      discriminating between CAD(+) and CAD(-) subjects. Lack of significant difference
      in PON activity between CAD patients and CAD(-) controls supports the concept of
      interethnic variability in PON polymorphism and unimodal distribution of its
      activity in non-Europid populations observed in other studies.

PMID- 11996959
TI  - Effect of CYP1A1 MspI polymorphism on cigarette smoking related coronary artery
      disease and diabetes.
AB  - CYP1A1, is one of the key detoxifying enzymes catabolizing cigarette smoking
      derived toxins and may be relevant to smoking-induced atherogenesis. Recently a
      CYP1A1 MspI polymorphism at the 3'-flanking region of the gene has been found to
      be associated with smoking related cancer risk and may, therefore, also be
      associated with vascular disease. To explore this, we investigated interactive
      effects between smoking and the CYP1A1 MspI polymorphism on coronary artery
      disease (CAD), diabetes and hypertension in 701 patients (aged < or =65 years)
      consecutively referred to Eastern Heart Clinic for angiographic investigation.
      The frequencies of the TT (80.2%), TC (17.7%) and CC (2.1%) genotypes were in
      Hardy-Weinberg equilibrium with the rare C allele frequency 0.11. The C allele
      carriers had an increased risk for triple vessel disease (three major epicardial
      coronary arteries with > or =50% luminal obstruction, OR, 3.44; 95%CI, 1.46-8.09;
      P=0.0046) in light smokers (< or =20 packyears). We further identified an
      interactive effect between smoking, the CYP1A1 MspI polymorphism and type 2
      diabetes (chi(2)=9.508, P=0.002). The C allele carriers who were smokers had an
      increased risk of diabetes (OR, 2.44; 95%CI, 1.32-4.49; P=0.0059). Our study
      suggests that CYP1A1 may participate in the pathogenesis of atherosclerosis and
      in the development of diabetes and its vascular complications. The presence of
      the rare C allele of the CYP1A1 gene in smokers may enhance predisposition to
      severe CAD and type 2 diabetes. These findings contribute to the understanding of
      cardiovascular risk and to smoking related vascular disease.

PMID- 11996960
TI  - Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms of
      CHD.
AB  - We evaluated a 69-year-old Japanese woman with apolipoprotein (apo) A-I
      deficiency, high levels of low-density lipoprotein (LDL)-cholesterol,
      hypertension and impaired glucose tolerance. The patient had corneal opacity, but
      neither xanthomas, xanthelasma, nor tonsillar hypertrophy. She was not
      symptomatic for coronary heart disease (CHD), and had normal electrocardiograms
      at rest and exercise using a cycle ergometer. She had severely reduced levels of
      high-density lipoprotein (HDL)-cholesterol (0.10-0.18 mmol/l) and no apo A-I
      (<0.6 mg/dl). LDL-cholesterol and apo B as well as apo E were increased even
      under treatment with 10 mg pravastatin per day. Gel filtration chromatography
      revealed that in addition to VLDL and LDL fractions, she had apo A-II rich and
      apo E rich fractions, which were present in the HDL fraction separated by
      ultracentrifugation. A cytosine deletion was identified by genomic DNA sequencing
      of the apo A-I gene of the patient at the third base of codon 184 in the fourth
      exon, which led to a frame shift mutation and early termination at codon 200.
      This patient is the oldest among those with apo A-I deficiency reported in the
      literature, and she had no symptoms of CHD despite the accumulated risk for the
      disease.

PMID- 11996961
TI  - Changes in plasma lecithin: cholesterol acyltransferase activity, HDL(2), HDL(3)
      amounts and compositions in patients with chronic renal failure after different
      times of hemodialysis.
AB  - The aim of this study was to investigate the effect of hemodialysis duration on
      HDL(2) and HDL(3) compositions and lecithin:cholesterol acyltransferase (LCAT)
      activity in 58 patients on acetate hemodialysis using cuprophane membrane, after
      different periods of dialysis. Patients were divided into three groups-GI <1
      year, GII 1-5 years, GIII 5-13 years of dialysis and were compared with 22
      controls. Increase by 34% of triacylglycerols (TG) was noted in GI and by 36% in
      GII versus GI. Hypertriglyceridemia was correlated with hemodialysis duration
      (HD) (r=0.75, P<0.05). The LCAT activity decrease by 25% was noted in GII versus
      GI (P<0.05) and by 45% in GIII versus GI (P<0.01), this activity was negligible
      in 33% of GII and 39% of GIII. LCAT activity was negatively correlated with HD
      (r=-0.80, P<0.001). Hemodialysis duration did not influence HDL(3) and HDL(2)
      amounts, HDL(3)-phospholipids (PL), HDL(3) and HDL(2)-cholesteryl esters (CE) and
      HDL(2)-apolipoproteins. However, an increase by 56% in HDL(2)-PL was noted in
      GIII versus GI and GII (P<0.01). HDL(2)-unesterified cholesterol (UC) were 2-fold
      higher in GIII than GII and GI (P<0.01). HDL(2)-TG were 2.2-fold higher in GII
      and 2.4-fold in GIII than GI (P<0.001). HDL(3)-apolipoproteins were 1.5-fold and
      1.8-fold lower in GI than GII (P<0.05) and GIII (P<0.01), respectively. An
      increase in HDL(3)-UC by 20% in GII and 33% in GIII versus GI (P<0.01) was noted.
      HDL(3)-TG increase by 66% was noted in GII and GIII versus GI (P<0.05). We
      conclude, that the long-term hemodialysis does not act on lipid anomalies
      following CRF. Alterations in HDL composition contribute to the reduced efficacy
      of reverse cholesterol transport, which is a risk factor for cardiovascular
      disease.

PMID- 11996962
TI  - Association between HDL-cholesterol and the Taq1B polymorphism in the cholesterol
      ester transfer protein gene in obese women.
AB  - Cholesterol ester transfer protein (CETP) facilitates reverse cholesterol
      transport via HDL-C and this activity may be increased in obese subjects. In
      normal weight subjects the Taq1B variant of the CETP gene is associated with
      lower CETP activity and higher HDL-C. The aim of this study was to examine the
      relationship between the Taq1B polymorphism and HDL-C in obese women before and
      after weight loss. A total of 245 women (41 with type 2 diabetes) were genotyped
      for the Taq1B variant. Plasma lipids, insulin, glucose and oral glucose tolerance
      were also measured before and after weight loss. When all subjects were examined
      together the Taq1B genotype was not associated with HDL-C. However, when non
      diabetic subjects were divided by median fasting insulin, a strong linear
      association was observed between Taq1B genotype and HDL-C in subjects below
      median for fasting insulin (B1B1 1.19+/-0.07 mmol/l, B1B2 1.35+/-0.06, B2B2
      1.71+/-0.09, P<0.000). This association was not observed in subjects with fasting
      insulin above median or subjects with type 2 diabetes, either before or after
      weight loss. Therefore, the B2B2 genotype is associated with elevated HDL-C in
      obese women with low fasting insulin only. Improved insulin sensitivity during
      weight loss did not change this relationship in women with high fasting insulin
      or type 2 diabetes.

PMID- 11996963
TI  - Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies.
AB  - The aim of this study was to evaluate changes in lipids, apolipoproteins and
      lipoproteins in Portuguese pregnant women and their potential involvement in the
      pathophysiology of preeclampsia. A cross-sectional study was performed by
      collecting blood samples in the first (n=64), second (n=48) and third (n=67)
      trimesters and puerperium (n=32) of normal pregnancies. Samples from preeclamptic
      women were obtained in the third trimester (n=51) and in puerperium (n=26). As
      normal pregnancy progressed and triglyceride (TG) levels rose there was a
      decrease in low density lipoprotein (LDL) size, as measured by peak and mean
      particle diameter (MPD), with an increased proportion of atherogenic small dense
      LDL. Preeclamptic women exhibited, in the third trimester and puerperium, higher
      mean serum TG concentration and lower high density lipoprotein (HDL) cholesterol
      and apolipoprotein A-I (apo A-I) levels compared with healthy pregnant women. In
      the third trimester, LDL-mean particle diameter (LDL-MPD) and LDL cholesterol
      apolipoprotein B (LDLc-apo B) ratio were also significantly reduced in the
      pathologic group. We conclude that human gestation is associated with an
      'atherogenic' lipid profile that is further enhanced in preeclampsia and that
      this profile may be a potential contributor to endothelial cell dysfunction.

PMID- 11996964
TI  - Assessment of atherosclerosis using carotid ultrasonography in a cohort of HIV
      positive patients treated with protease inhibitors.
AB  - OBJECTIVE: Lipid disorders associated with the use of protease inhibitors (PI)
      may be a risk factor for premature atherosclerosis development. The aim of this
      study is to evaluate the extent of carotid intima media thickness (IMT) among HIV
      positive patients treated with PI containing regimens compared to PI-naive and
      HIV-negative subjects. METHODS: We analysed plasma lipid levels and carotid IMT
      in 28 HIV-positive patients treated with protease inhibitors (PIs) for a mean of
      28.7 months (range 18-43) and in two control groups constituted, respectively, by
      15 HIV-positive naive patients and 16 HIV-negative subjects, that were matched
      for age, risk factors for HIV infection, cigarette smoke use and CD4+ cell count.
      RESULTS: PI-treated patients had higher triglyceride, HDL and apo B levels than
      controls. Carotid IMT was significantly increased in PI-treated patients compared
      to naive or HIV-negative subjects. A correlation between cholesterol HDL,
      triglyceride and ApoB levels and IMT was observed among the entire cohort.
      CONCLUSIONS: Plasma lipid alterations were associated with an increased IMT and
      intima media thickening was more pronounced in PI-treated patients than in the
      two control groups. Periodical evaluation of blood lipid profile and, if
      required, the use of lipid-lowering agents is advisable. Moreover, physicians
      should address concurrent risk factor for atherosclerosis that can be modified,
      including smoking, hypertension, obesity and sedentary life-style.

PMID- 11996965
TI  - European Lipoprotein Club: Report of the 24th ELC Annual Conference, Tutzing, 10
      13 September 2001.

PMID- 11996966
TI  - Abnormal chromosome migration and chromosome aberrations in mouse oocytes during
      meiosis II in the presence of topoisomerase II inhibitor ICRF-193.
AB  - Using a mouse parthenogenetic system, effects of ICRF-193, a noncleavable complex
      forming topoisomerase II inhibitor, on female meiosis II chromosomes and
      pronuclear chromosomes were studied. Eggs were exposed to the inhibitor (10
      microM) at various times after parthenogenetic stimulation, and chromosomes of
      them were analyzed at the first cleavage metaphase. When eggs were exposed to the
      inhibitor during the period from metaphase II to anaphase II, a significant
      increase in incidences of structural chromosome aberrations (51.1% versus 1.3% in
      the control) and aneuploidy (30.3% versus 0.7% in the control) was found.
      Structural chromosome aberrations were observed in 10-20% of eggs following
      treatments during telophase II, but there was no increased incidence of
      aneuploidy in treatments during this meiotic stage. When pronuclear eggs at S
      phase were targeted by the inhibitor, no significant increase in chromosome
      aberrations was found.Interestingly, when chromatids moved to each pole during
      anaphase II in the presence of ICRF-193, most of them oriented their centromeres
      toward the spindle equator as if moving backwards. Moreover, lagging chromatids
      with the centromeres present were observed in more than 50% of treated eggs.
      However, chromosomal bridges that resulted from chromosome stickiness did not
      appear in any egg.These findings indicate that ICRF-193 can induce structural
      chromosome aberrations and aneuploidy in mouse secondary oocytes in meiotic stage
      dependent manner. The induction of aneuploidy is due to disruption of the
      separation of sister centromeres at anaphase II. There appears to be mechanism(s)
      other than cleavable complex formation or chromosome stickiness behind the
      induction of structural chromosome aberrations by ICRF-193.

PMID- 11996967
TI  - Induction of SOS response in Salmonella typhimurium TA4107/pSK1002 by
      peroxynitrite-generating agent, N-morpholino sydnonimine.
AB  - Salmonella typhimurium TA4107/pSK1002 strain was used to measure the SOS response
      induced by peroxynitrite. The parent strain TA4107 (oxydelta1[oxydelta(oxyR
      argH)1]) is sensitive to oxidative stress and the plasmid of pSK1002 carries a
      fused gene umuC'-'lacZ, in which umu and lacZ genes are involved in the induction
      of mutagenesis and beta-galactosidase activity, respectively. Therefore, the
      level of SOS response was monitored via beta-galactosidase activity. A bolus
      addition of authentic peroxynitrite (0.3-0.6 mM) increased about eight times the
      enzyme activity. In N-morpholino sydnonimine (SIN-1), which produces
      peroxynitrite from superoxide and nitric oxide generated through hydrolysis,
      addition of over 1mM SIN-1 induced four-five-fold activity. The SIN-1-induced SOS
      response was scarcely influenced by superoxide dismutase (SOD), catalase or a
      combination of both, removing the possibility of induction by superoxide,
      hydrogen peroxide and hydroxyl radical. Two types of peroxynitrite scavengers,
      mannitol (type I) and glutathione (type II), decreased the response. Mannitol
      showed a constant inhibition (70%) at a concentration up to 20 mM, exhibiting
      kinetics that are zero-order in mannitol and first-order in peroxynitrite. On the
      other hand, glutathione sharply reduced the response dependent on concentration
      up to 2 mM (90%), indicating second-order kinetics, first-order in both
      glutathione and peroxynitrite. Dihydrorhodamine (DHR)123, which traps
      peroxynitrite in a molar ratio of 1:1, efficiently inhibited the SOS response.
      These effects suggest that peroxynitrite, generated gradually from SIN-1,
      penetrates through the cell membrane, damages the DNA and induces the SOS
      response. This strain can thus, be used in screening of antioxidants against
      peroxynitrite-induced DNA damage in cells.

PMID- 11996968
TI  - Characterization of DNA polymorphisms in the E-cadherin gene (CDH1) promoter
      region.
AB  - E-cadherin is a tumor suppressor involved in epithelial cell-cell interactions.
      Some of the nucleotide variation in the 5'-promoter region of the gene influences
      transcriptional efficiency. We investigated single nucleotide polymorphisms
      (SNPs) in the promoter-exon 1 region of the E-cadherin gene (CDH1) using
      fluorescence-based PCR-single-strand conformation polymorphism (PCR-SSCP)
      analysis. We detected four kinds of polymorphisms between nucleotides -516 and
      +12, numbering from the translation initiation site. SNPs were localized at -472G
      ->GA, -288T-->deltaT, -285C-->A, and -54G-->C. Variants -472GA and -285A were
      frequently found in controls, but the -288deltaT and -54C are rare variants. We
      examined the effects of these variants on transcription. The activity of
      promoters containing the variants -288deltaT, -285A, or -54C was lower than the
      activity of promoters with the major variants, as assayed by a luciferase
      reporter gene. Variants -472G and -472GA displayed the same promoter activity.
      The decreased transcriptional activity from variant promoters affects the
      expression of E-cadherin.

PMID- 11996969
TI  - Genetic assays for measuring rates of (CAG).(CTG) repeat instability in
      Escherichia coli.
AB  - Genetic selection assays were developed to measure rates of deletion of one or
      more (CAG).(CTG) repeats, or an entire repeat tract, in Escherichia coli. In
      frame insertions of >or=25 repeats in the chloramphenicol acetyltransferase (CAT)
      gene of pBR325 resulted in a chloramphenicol-sensitive (Cm(s)) phenotype. When
      (CAG)25 comprised the leading template strand, deletion of one or more repeats
      resulted in a chloramphenicol resistant (Cm(r)) phenotype at a rate of 4 x 10(-2)
      revertants per cell per generation. The mutation rates for plasmids containing
      (CAG)43 or (CAG)79 decreased significantly. When (CTG)n comprised the leading
      template strand the Cm(r) mutation rates were 100-1000 lower than for the
      opposite orientation. As an initial application of this assay, the effects of
      mutations influencing mismatch repair and recombination were examined. The methyl
      directed mismatch repair system increased repeat stability only when (CTG)n
      comprised the leading template strand. Replication errors made with the opposite
      repeat orientation were apparently not recognized. For the (CAG)n leading strand
      orientation, mutation rates were reduced as much as 3000-fold in a recA- strain.
      In a second assay, out-of-frame mutation inserts underwent complete deletion at
      rates ranging from about 5 x 10(-9) to 1 x 10(-7) per cell per generation. These
      assays allow careful quantitation of triplet repeat instability in E. coli and
      provide a way to examine the effects of mutations in replication, repair, and
      recombination on repeat instability.

PMID- 11996970
TI  - Instability of repeated DNAs during transformation in Escherichia coli.
AB  - Escherichia coli has provided an important model system for understanding the
      molecular basis for genetic instabilities associated with repeated DNA. Changes
      in triplet repeat length during growth following transformation in E. coli have
      been used as a measure of repeat instability. However, very little is known about
      the molecular and biological changes that may occur on transformation. Since only
      a small proportion of viable cells become competent, uncertainty exists regarding
      the nature of these transformed cells. To establish whether the process of
      transformation can be inherently mutagenic for certain DNA sequences, we used a
      genetic assay in E. coli to compare the frequency of genetic instabilities
      associated with transformation with those occurring in plasmid maintained in E.
      coli. Our results indicate that, for certain DNA sequences, bacterial
      transformation can be highly mutagenic. The deletion frequency of a 106 bp
      perfect inverted repeat is increased by as much as a factor of 2 x 10(5)
      following transformation. The high frequency of instability was not observed when
      cells stably harboring plasmid were rendered competent. Thus, the process of
      transformation was required to observe the instability. Instabilities of
      (CAG).(CTG) repeats are also dramatically elevated upon transformation. The
      magnitude of the instability is dependent on the nature and length of the repeat.
      Differences in the methylation status of plasmid used for transformation and the
      methylation and restriction/modification systems present in the bacterial strain
      used must also be considered in repeat instability measurements. Moreover,
      different E. coli genetic backgrounds show different levels of instability during
      transformation.

PMID- 11996971
TI  - The micronucleus assay in human lymphocytes after high radiation doses (5-15 Gy).
AB  - Individuals can be exposed to high doses (more than 5Gy) during radiation
      accidents. It is, of course, helpful to the physician to have biological
      indicators also for such high doses. The problem with most cytogenetic indicators
      is, that the response levels off at doses starting around 5-7Gy of low LET
      radiation and that the dose-response curve even declines after doses exceeding
      about 10Gy. Thus, it may be difficult to decide, whether the dose was, for
      example, 8 or 14Gy. We studied how the micronucleus assay can be used to give
      information also in the high dose range. It turned out that micronucleus
      frequency itself cannot be used for the estimation of doses exceeding about 5
      7Gy. There are, however, at least three other endpoints that can be determined in
      the cytochalasin B assay that can assist the decision in the high dose range: (1)
      the number of mononucleated cells; (2) the ratio of tri- to tetranucleated cells;
      (3) the average micronucleus frequency in micronucleus positive binucleated
      cells.

PMID- 11996972
TI  - Use of yeast transformation by oligonucleotides to study DNA lesion bypass in
      vivo.
AB  - We have studied mutagenic specificities of DNA lesions in vivo in yeast CYC1
      oligonucleotide transformation assay. We introduced two lesions into
      oligonucleotides. One was a nucleoside analog, 3,4-dihydro-6H,8H-pyrimido[4,5
      c][1,2]oxazin-7-one 2'-deoxyriboside (dP), which is highly mutagenic to bacteria.
      It is supposed to be a miscoding, but otherwise good template for DNA
      polymerases. The other lesion was the TT pyrimidine(6-4)pyrimidone photoproduct,
      one of the typical UV lesions, which blocks DNA replication. These
      oligonucleotides were used to transform yeast cyc1 mutants with ochre nonsense
      mutation to Cyc1+. As expected from its templating properties in vitro, the
      transforming activity of dP-containing oligonucleotides was similar to those of
      unmodified oligonucleotides. Results indicated that dP may direct incorporation
      of guanine and adenine at a ratio of 1:20 or more in vivo. An oligonucleotide
      containing the photoproduct showed the transforming activity of as low as 3-5% of
      that of the corresponding unmodified oligonucleotide. This bypass absolutely
      required REV1 gene. The sequence analysis of the transformants has shown that the
      lesion was read as TT and TC at a ratio of 3:7, indicating its high mutagenic
      potential.

PMID- 11996973
TI  - Polymorphisms of the DNA repair gene XRCC1 and the frequency of somatic mutations
      at the glycophorin A locus in newborns.
AB  - Two DNA polymorphisms in the XRCC1 gene, a microsatellite repeat region in the 3'
      un-translated region (3'UTR) of the gene and a G-->A substitution resulting in an
      Arg to Gln amino acid change in codon 399, were examined in 189 newborns who had
      previously been studied for glycophorin A (GPA) N0 and NN variant frequencies
      (Vfs) in cord blood erythrocytes. The GPA analysis had revealed that 14 of the
      189 had extreme NN Vfs ranging from 40 x 10(-6) to 1787 x 10(-6). Mean Vfs for
      the remaining 175 were N0=(4.8+/-2.80)x10(-6) and NN=(2.62+/-2.01)x10(-6). Seven
      alleles of a polymorphic tandem [AC](n) region of the XRCC1 gene were identified.
      No association between [AC](n) genotype and either N0 or NN Vfs was found amongst
      the group of 175 nor was the distribution of genotypes unusual for the group of
      14 with extreme NN Vfs. Analysis of the 399Gln polymorphism revealed that for the
      group of 175, 36.0% were Arg/Arg, 49.7% Arg/Gln and 14.3% Gln/Gln and genotype
      had no influence on N0 and NN Vfs. However, the distribution of genotypes was
      significantly different in the group of 14 with extreme NN Vfs, 14.3% being
      Arg/Arg, 42.8% Arg/Gln and 42.8% Gln/Gln. The 14 newborns with extreme NN Vfs may
      represent a sub-group with an unidentified genotoxic exposure and/or
      predisposition to gene-duplication mutations or alternatively the high values
      could have arisen by increased clonal expansion of haemopoietic precursor cells
      carrying NN mutations. Our results suggest that carriers of the Gln/Gln genotype
      are over represented in this group but the role that the genotype has in the
      derivation of high NN Vfs remains to be resolved.

PMID- 11996974
TI  - Radiation-induced genetic instability in vivo depends on p53 status.
AB  - In response to ionizing radiation and other agents that damage DNA, the p53 tumor
      suppressor protein activates multiple cellular processes including cell cycle
      checkpoints and programmed cell death. Although loss of p53 function is
      associated with radiation-induced genetic instability in cell lines, it is not
      clear if this relationship exists in vivo. To study the role of p53 in
      maintenance of genetic stability in normal tissues following irradiation, we have
      measured mutant frequencies at the adenine phosphoribosyltransferase (Aprt) and
      hypothanine-guanine phosphoribosyltransferase (Hprt) loci and examined mechanisms
      of loss of heterozygosity (LOH) in normal T cells of p53-deficient, Aprt
      heterozygous mice that were subjected to whole-body irradiation with a single
      dose of 4Gy X-rays. The radiation-induced mutant frequency at both the Aprt and
      Hprt loci was elevated in cells from mice with different p53 genotypes. The
      radiation-induced elevation of p53-/- mice was significantly greater than that of
      p53+/- or p53+/+ mice and was caused by several different kinds of mutational
      events at the both chromosomal and intragenic levels. Most significantly,
      interstitial deletion, which occurs rarely in unirradiated mice, became the most
      common mechanism leading to LOH in irradiated p53 null mice. These observations
      support the idea that absence or reduction of p53 expression enhances radiation
      induced tumorigenesis by increasing genetic instability at various loci, such as
      those for tumor suppressor genes.

PMID- 11997007
TI  - Protein phosphatase 2A methylation: a link between elevated plasma homocysteine
      and Alzheimer's Disease.
AB  - Tau hyperphosphorylation is a central event in the development of Alzheimer's
      Disease (AD). Protein phosphatase 2A (PP2A) heterotrimer formation is necessary
      for efficient dephosphorylation of the tau protein. S-Adenosylmethionine
      dependent carboxyl methylation is essential for the assembly of PP2A
      heterotrimers. Epidemiological evidence indicates that elevated plasma
      homocysteine is an independent risk factor for AD. Homocysteine is a key
      intermediate in the methyl cycle and elevated plasma homocysteine results in a
      global decrease in cellular methylation. We propose that the PP2A methylation
      system is the link relating elevated plasma homocysteine to AD.

PMID- 11997008
TI  - Reciprocal mutations of neuropeptide Y receptor Y2 in human and chicken identify
      amino acids important for antagonist binding.
AB  - The neuropeptide Y (NPY) receptor Y2 antagonist BIIE0246 has sub-nanomolar
      affinity for the human Y2 (hY2) receptor but binds very poorly to chicken Y2
      (chY2) with micromolar affinity. Sequence comparisons identified several amino
      acids for investigation by mutagenesis. Reciprocal mutagenesis between hY2 and
      chY2 revealed that three of these, individually and in combination, are important
      for BIIE0246 binding, namely positions Gln(135) in transmembrane (TM) 3, Leu(227)
      in TM5, and Leu(284) in TM6. Mutagenesis of hY2 to the corresponding amino in
      chY2 (generating hY2[Q135H,L227Q,L284F]) made the affinity of BIIE0246 as low as
      for chY2. Introduction into chY2 of the three human residues resulted in
      antagonist affinity almost as high as for hY2. To distinguish between direct and
      indirect effects, each of the three residues in hY2 was replaced with alanine.
      BIIE0246 bound with 28-fold lower affinity to hY2[L227A], suggesting the Leu(227)
      interacts directly with the antagonist. The other two alanine mutants bound with
      unaltered affinity, suggesting that the corresponding chY2 residues abolish
      binding through steric hindrance or charge repulsion. Thus, three amino acid
      residues can in an additive manner completely account for the difference in
      antagonist binding between the hY2 and chY2 receptors. These results will be
      useful for construction of three-dimensional models of the widely divergent NPY
      receptor subtypes.

PMID- 11997009
TI  - PrrC from Rhodobacter sphaeroides, a homologue of eukaryotic Sco proteins, is a
      copper-binding protein and may have a thiol-disulfide oxidoreductase activity.
AB  - PrrC from Rhodobacter sphaeroides provides the signal input to a two-component
      signal transduction system that senses changes in oxygen tension and regulates
      expression of genes involved in photosynthesis (Eraso, J.M. and Kaplan, S. (2000)
      Biochemistry 39, 2052-2062; Oh, J.-I. and Kaplan, S. (2000) EMBO J. 19, 4237
      4247). It is also a homologue of eukaryotic Sco proteins and each has a C-x-x-x-C
      P sequence. In mitochondrial Sco proteins these cysteines appear to be essential
      for the biogenesis of the CuA centre of respiratory cytochrome oxidase.
      Overexpression and purification of a water-soluble and monomeric form of PrrC has
      provided sufficient material for a chemical and spectroscopic study of the
      properties of the four cysteine residues of PrrC, and its ability to bind
      divalent cations, including copper. PrrC expressed in the cytoplasm of
      Escherichia coli binds Ni2+ tightly and the data are consistent with a
      mononuclear metal site. Following removal of Ni2+ and formation of renatured
      metal-free rPrrC (apo-PrrC), Cu2+ could be loaded into the reduced form of PrrC
      to generate a protein with a distinctive UV-visible spectrum, having absorbance
      with a lambda(max) of 360 nm. The copper:PrrC ratio is consistent with the
      presence of a mononuclear metal centre. The cysteines of metal-free PrrC oxidise
      in the presence of air to form two intramolecular disulfide bonds, with one pair
      being extremely reactive. The cysteine thiols with extreme O2 sensitivity are
      involved in copper binding in reduced PrrC since the same copper-loaded protein
      could not be generated using oxidised PrrC. Thus, it appears that PrrC, and
      probably Sco proteins in general, could have both a thiol-disulfide
      oxidoreductase function and a copper-binding role.

PMID- 11997010
TI  - Alternative arrangements of catalytic residues at the active sites of restriction
      enzymes.
AB  - A catalytic sequence motif PDX10-30(E/D)XK is found in many restriction enzymes.
      On the basis of sequence similarities and mapping of the conserved residues to
      the crystal structure of NgoMIV we suggest that residues D160, K182, R186, R188
      and E195 contribute to the catalytic/DNA binding site of the Ecl18kI restriction
      endonuclease. Mutational analysis confirms the functional significance of the
      conserved residues of Ecl18kI. Therefore, we conclude that the active site motif
      159VDX21KX12E of Ecl18kI differs from the canonical PDX10-30(E/D)XK motif
      characteristic for most of the restriction enzymes. Moreover, we propose that two
      subfamilies of endonucleases Ecl18kI/PspGI/EcoRII and Cfr10I/Bse634I/NgoMIV,
      specific, respectively, for CCNGG/CCWGG and RCCGGY/GCCGGC sites, share conserved
      active site architecture and DNA binding elements.

PMID- 11997011
TI  - Histone H3 phosphorylation during Xenopus oocyte maturation: regulation by the
      MAP kinase/p90Rsk pathway and uncoupling from DNA condensation.
AB  - Here we show that during the meiotic maturation of Xenopus oocytes, histone H3
      becomes phosphorylated on serine-10 at about the time of maturation promoting
      factor activation and meiosis I entry. However, overexpression of cAMP-dependent
      protein kinase that blocks entry into M phase, also leads to massive serine-10
      phosphorylation of histone H3 in intact Xenopus oocytes but does not cause
      chromosome condensation. We also show that the phosphorylation of histone H3
      during oocyte maturation requires the activation of the mitogen-activated protein
      kinase/p90Rsk pathway. Our results indicate that in G2-arrested oocytes, which
      are about to enter M phase, histone H3 phosphorylation is not sufficient for
      chromosome condensation.

PMID- 11997012
TI  - Oxygen reduction by cellobiose oxidoreductase: the role of the haem group.
AB  - We have used optical and electron paramagnetic spectroscopy to study the
      flavohaem enzyme cellobiose oxidoreductase (CBOR) from Phanerochaete
      chrysosporium. We have examined redox cycles of the enzyme in which the oxidation
      of cellobiose to cellobionolactone is coupled to the reduction of oxygen. During
      turnover flavin can reduce oxygen with one electron to produce superoxide or two
      electrons to produce hydrogen peroxide. Addition of superoxide dismutase
      significantly extended the time courses of these cycles, slowing the re-oxidation
      rate of both cofactors. Addition of catalase also affected the haem time course,
      but to a lesser extent. Experiments in which superoxide was generated in the
      reaction mixture showed that this radical greatly enhanced the rate of haem re
      oxidation. From these results we propose a mechanism in which reactive oxygen
      species generation by CBOR flavin subsequently re-oxidises CBOR haem. We discuss
      this mechanism in relationship to the biological function of this enzyme, namely
      lignocellulose degradation.

PMID- 11997013
TI  - Solution structure of moricin, an antibacterial peptide, isolated from the
      silkworm Bombyx mori.
AB  - A novel antibacterial peptide, moricin, isolated from the silkworm Bombyx mori,
      consists of 42 amino acids. It is highly basic and the amino acid sequence has no
      significant similarity to those of other antibacterial peptides. The 20
      structures of moricin in methanol have been determined from two-dimensional 1H
      nuclear magnetic resonance spectroscopic data. The solution structure reveals an
      unique structure comprising of a long alpha-helix containing eight turns along
      nearly the full length of the peptide except for four N-terminal residues and six
      C-terminal residues. The electrostatic surface map shows that the N-terminal
      segment of the alpha-helix, residues 5-22, is an amphipathic alpha-helix with a
      clear separation of hydrophobic and hydrophilic faces, and that the C-terminal
      segment of the alpha-helix, residues 23-36, is a hydrophobic alpha-helix except
      for the negatively charged surface at the position of Asp30. The results suggest
      that the amphipathic N-terminal segment of the alpha-helix is mainly responsible
      for the increase in permeability of the membrane to kill the bacteria.

PMID- 11997014
TI  - The importance of the conserved Arg191-Asp227 salt bridge of triosephosphate
      isomerase for folding, stability, and catalysis.
AB  - Triosephosphate isomerase (TIM) has a conserved salt bridge 20 A away from both
      the active site and the dimer interface. In this study, four salt bridge mutants
      of Trypanosoma brucei brucei TIM were characterized. The folding and stability of
      the mutants are impaired compared to the wild-type enzyme. This salt bridge is
      part of a hydrogen bonding network which tethers the C-terminal
      beta7alpha7beta8alpha8 unit to the bulk of the protein. In the variants D227N,
      D227A, and R191S, this network is preserved, as can be deduced from the structure
      of the R191S variant. In the R191A variant, the side chain at position 191 cannot
      contribute to this network. Also the catalytic power of this variant is most
      affected.

PMID- 11997015
TI  - Identification of a Baeyer-Villiger monooxygenase sequence motif.
AB  - Baeyer-Villiger monooxygenases (BVMOs) form a distinct class of flavoproteins
      that catalyze the insertion of an oxygen atom in a C-C bond using dioxygen and
      NAD(P)H. Using newly characterized BVMO sequences, we have uncovered a BVMO
      identifying sequence motif: FXGXXXHXXXW(P/D). Studies with site-directed mutants
      of 4-hydroxyacetophenone monooxygenase from Pseudomonas fluorescens ACB suggest
      that this fingerprint sequence is critically involved in catalysis. Further
      sequence analysis showed that the BVMOs belong to a novel superfamily that
      comprises three known classes of FAD-dependent monooxygenases: the so-called
      flavin-containing monooxygenases (FMOs), the N-hydroxylating monooxygenases
      (NMOs), and the BVMOs. Interestingly, FMOs contain an almost identical sequence
      motif when compared to the BVMO sequences: FXGXXXHXXX(Y/F). Using these novel
      amino acid sequence fingerprints, BVMOs and FMOs can be readily identified in the
      protein sequence databank.

PMID- 11997016
TI  - A nuclear transcription factor related to plastid ribosome biogenesis is
      synthesised early during germination and priming.
AB  - Germination is a short developmental process during which many new proteins are
      synthesised. We have chosen the previously characterised RPL21 gene encoding
      plastid-localised ribosomal proteins RPL21, to analyse activation of gene
      expression during germination. Transcription activation occurs at the P1 promoter
      during the first hours following imbibition and coincides with the appearance of
      a trans-acting factor that we named AUBE1. AUBE1 binds specifically to a short
      DNA fragment that encompasses the P1 promoter of the RPL21 gene. The protein has
      a size of 28-30 kDa and is transiently expressed during the early phase of
      germination. Using the properties of primed seeds we show that AUBE1 is
      maintained after desiccation of primed seeds. We conclude that AUBE1 can be used
      as a marker in spinach seed priming.

PMID- 11997017
TI  - Corticosteroid inhibits IL-4 signaling through down-regulation of IL-4 receptor
      and STAT6 activity.
AB  - Corticosteroids are potent anti-inflammatory and immunosuppressive agents which
      down-regulate cytokine production and action. Yet, contradictory results have
      been reported for their effects on the interleukin (IL)-4-mediated response.
      Using type II Fc receptor for IgE/CD23 as a target gene, here we report that
      corticosteroids at 10(-4)-10(-6) M inhibit the IL-4 signaling pathway in human
      primary immune cells by down-regulation of the IL-4-induced IL-4 receptor
      expression and STAT6 activation. Although functional antagonism between steroid
      receptor and STAT6 for their transcriptional activity has been recently
      described, this is the first report that steroid inhibits the IL-4-induced STAT6
      activity at the level of tyrosine phosphorylation and target DNA binding.

PMID- 11997018
TI  - Increased intracellular calcium is required for neurite outgrowth induced by a
      synthetic peptide ligand of NCAM.
AB  - We have recently identified a synthetic peptide, termed C3, capable of binding
      the first immunoglobulin-like module of neural cell adhesion molecule (NCAM) by
      means of combinatorial chemistry and shown that this NCAM ligand promotes neurite
      outgrowth. By means of single cell calcium imaging using the calcium-sensitive
      probe fura-2-acetomethyl ester, we here show that the C3-peptide induced an
      increase in intracellular calcium in primary hippocampal neurons and PC12-E2
      cells, presumably requiring mobilization of calcium from both extracellular and
      intracellular stores. We further observed that C3-induced neurite outgrowth was
      inhibited by antagonists of voltage-dependent calcium channels as well as by an
      inhibitor of intracellular calcium mobilization, TMB-8. These findings
      demonstrate at the single cell level that a synthetic NCAM ligand directly can
      induce an increase in intracellular calcium and suggest that NCAM-dependent
      neurite outgrowth requires calcium mobilization from both extracellular and
      intracellular calcium stores. Thus, the C3-peptide may be regarded as a useful
      tool for the study of NCAM-dependent signal transduction. Furthermore, the
      peptide may be of considerable therapeutical interest for the treatment of
      neurodegenerative disorders.

PMID- 11997019
TI  - Design of a chimeric promoter induced by pro-inflammatory mediators in articular
      chondrocytes.
AB  - We have designed a chimeric promoter that can be stimulated by various pro
      inflammatory mediators and so drive the expression of therapeutic genes under
      inflammatory conditions. The promoter has two parts, the [-247/+20] fragment of
      the human type IIA secreted phospholipase A2 gene promoter, which is stimulated
      by the pro-inflammatory cytokine interleukin-1beta (IL-1beta), and a double
      peroxisome proliferator-activated receptor response element that is activated by
      some eicosanoids and by non-steroidal anti-inflammatory drugs (NSAIDs).
      Transfection experiments using rabbit articular chondrocytes in primary culture
      showed that this chimeric promoter produced a low basal activity and was induced
      by NSAIDs, WY-14643, IL-1beta, and 15-deoxy Delta12,14 prostaglandin J2. The
      latter two compounds stimulated the promoter synergistically.

PMID- 11997020
TI  - An investigation into the mechanisms mediating plasma lipoprotein-potentiated
      beta-amyloid fibrillogenesis.
AB  - The toxicity of the beta-amyloid (Abeta) peptide of Alzheimer's disease may
      relate to its polymerisation state (i.e. fibril content). We have shown
      previously that plasma lipoproteins, particularly when oxidised, greatly enhance
      Abeta polymerisation. In the present study the nature of the interactions between
      both native and oxidised lipoproteins and Abeta1-40 was investigated employing
      various chemical treatments. The addition of ascorbic acid or the vitamin E
      analogue, trolox, to lipoprotein/Abeta coincubations failed to inhibit Abeta
      fibrillogenesis, as did the treatment of lipoproteins with the aldehyde
      reductant, sodium borohydride. The putative lipid peroxide-derived aldehyde
      scavenger, aminoguanidine, however, inhibited Abeta-oxidised lipoprotein
      potentiated polymerisation, but in a manner consistent with an antioxidant action
      for the drug. Lipoprotein treatment with the reactive aldehyde 4-hydroxy-2-trans
      nonenal enhanced Abeta polymerisation in a concentration-dependent fashion.
      Incubation of Abeta with lipoprotein fractions from which the apoprotein
      components had been removed resulted in extents of polymerisation comparable to
      those observed with Abeta alone. These data indicate that the apoprotein
      components of plasma lipoproteins play a key role in promoting Abeta
      polymerisation, possibly via interactions with aldehydes.

PMID- 11997021
TI  - Action pattern and subsite mapping of Bacillus licheniformis alpha-amylase (BLA)
      with modified maltooligosaccharide substrates.
AB  - This study represents the first characterisation of the substrate-binding site of
      Bacillus licheniformis alpha-amylase (BLA). It describes the first subsite map,
      namely, number of subsites, apparent subsite energies and the dual product
      specificity of BLA. The product pattern and cleavage frequencies were determined
      by high-performance liquid chromatography, utilising a homologous series of
      chromophore-substituted maltooligosaccharides of degree of polymerisation 4-10 as
      model substrates. The binding region of BLA is composed of five glycone, three
      aglycone-binding sites and a 'barrier' subsite. Comparison of the binding
      energies of subsites, which were calculated with a computer program, shows that
      BLA has similarity to the closely related Bacillus amyloliquefaciens alpha
      amylase.

PMID- 11997022
TI  - Stimulation of Cdx1 by oncogenic beta-catenin/Tcf4 in colon cancer cells;
      opposite effect of the CDX2 homeoprotein.
AB  - The homeobox gene Cdx1 is a regulator of intestinal epithelial cell proliferation
      and differentiation. Using a transfection approach, we showed here that the
      oncogenic activation of the beta-catenin pathway stimulates the endogenous
      expression of the Cdx1 mRNA as well as the activity of the Cdx1 promoter in
      cancer cells of the human colon. Reciprocally, the paralogue homeobox gene Cdx2
      exerts an inhibitory effect on the basal and on the beta-catenin-stimulated
      activity of the Cdx1 promoter. The inhibitory effect of CDX2 requires the intact
      homeodomain. It is not dependent on canonical CDX binding sites in the Cdx1
      promoter nor on the cis-elements specifically targeted by the beta-catenin/Tcf
      complex. We conclude that the oncogenically activated beta-catenin and CDX2 have
      opposite and independent effects on the Cdx1 homeobox gene.

PMID- 11997023
TI  - Effects of brefeldin A and nordihydroguaiaretic acid on endomembrane dynamics and
      lipid synthesis in plant cells.
AB  - Effects of brefeldin A (BFA) and nordihydroguaiaretic acid (NDGA) on endomembrane
      structures and lipid synthesis were compared in maize root cells and tobacco
      Bright Yellow-2 cells. Immunofluorescence and electron microscopy studies showed
      that NDGA altered the structure and distribution of the endoplasmic reticulum
      (ER) within 1 h but not of the Golgi apparatus whereas, as shown previously, BFA
      altered that organization of the Golgi apparatus and, only subsequently, of the
      ER. Biochemical studies revealed that both drugs and especially BFA led to a
      strong inhibition of the phytosterol biosynthetic pathway: BFA led to
      accumulation of sterol precursors. The importance of phytosterols in membrane
      architecture and membrane trafficking is discussed.

PMID- 11997024
TI  - One functional subunit is sufficient for catalytic activity and substrate
      specificity of Escherichia coli endoribonuclease III artificial heterodimers.
AB  - To study the intersubunit communication required for the activity of the normally
      homodimeric enzyme endoribonuclease III of Escherichia coli we have constructed
      and analysed an artificial heterodimer. This heterodimer is composed of one wild
      type and one catalytically inactive subunit. The inactive subunit has one amino
      acid exchanged (E117K, rnc70 mutant) which abolishes cleavage activity but still
      allows substrate binding of a rnc70-homodimer. Our results show that one
      functional active site is sufficient for cleavage activity of the heterodimer.

PMID- 11997025
TI  - Gamma-amido-ATP stabilizes a high-fluorescence state of myosin subfragment 1.
AB  - On binding to myosin subfragment 1 (S1), the gamma-amido derivative of ATP
      (ATPgammaNH2), an isomer of adenosine 5'-[beta,gamma-imido]-triphosphate
      (AMPPNP), induces a larger increase in the intrinsic (tryptophan) fluorescence
      than is seen with ATP. A binding constant of 1.7x10(7) M(-1) was measured for
      ATPgammaNH2, compared to 2.1-2.4x10(7) M(-1) for AMPPNP. ATPgammaNH2 was
      hydrolyzed only very slowly by S1. ATPgammaNH2 appears to stabilize the 'closed'
      conformation of S1, and does so without cleavage of the beta-gamma phosphate
      bond. The dissociation of actin-S1 by ATPgammaNH2 and that of S1.ATPgammaNH2 by
      actin are both strikingly slow.

PMID- 11997026
TI  - Association of human transferrin receptor with GABARAP.
AB  - A yeast two-hybrid screen identified a specific interaction between the
      cytoplasmic domain of transferrin receptor (TfR) and GABARAP, a 14 kDa protein
      that binds to the gamma2 subunit of neuronal GABA(A) receptors. The specificity
      of the TfR-GABARAP interaction was demonstrated by in vitro binding assays with
      purified proteins and by co-immunoprecipitation of GABARAP with endogenous TfR
      from HeLa cell lysates. Replacement of the YTRF internalization motif with ATRA
      within the cytoplasmic domain of TfR reduced interaction with GABARAP in the
      yeast two-hybrid screen and in vitro binding assays. The intracellular location
      of GABARAP using chimeric GABARAP-GFP showed that the majority of GABARAP was
      located in perinuclear vesicles. Our results show that GABARAP plays a more
      general role outside the confines of neuronal cells and GABA(A) receptors.

PMID- 11997027
TI  - Catalase negative Staphylococcus aureus retain virulence in mouse model of
      chronic granulomatous disease.
AB  - Myeloperoxidase-mediated chlorination is thought to be a necessary microbicidal
      mechanism. The H2O2 required for this process is generated by the NADPH oxidase.
      Staphylococcus aureus can also produce H2O2, which is not broken down by catalase
      negative organisms. It has been thought that this bacterial H2O2 can substitute
      for cellular H2O2 in the halogenation reaction in chronic granulomatous disease
      (CGD) where neutrophils are lacking the NADPH oxidase. We have readdressed this
      issue in a mouse model of CGD using clinical isolates of catalase positive and
      negative strains of S. aureus. The results showed these organisms to be equally
      virulent and that the H2O2 they produced is insufficient to cause significant
      iodination, a marker for chlorination, thereby contradicting the accepted views
      on this subject.

PMID- 11997028
TI  - Probing the environment of neurotensin whilst bound to the neurotensin receptor
      by solid state NMR.
AB  - A functionally active analogue of neurotensin, neurotensin(8-13), has been
      observed whilst bound to the agonist-binding site of the rat neurotensin receptor
      by nuclear magnetic resonance (NMR). Through the application of slow magic angle
      sample spinning and high-power proton decoupling, sufficient resolution and
      sensitivity were obtained in the carbon-13 spectrum to allow an assignment of
      many of the side chain resonances arising from uniformly carbon-13/nitrogen-15
      labelled neurotensin(8-13) whilst bound to the neurotensin receptor. Significant
      perturbations in carbon-13 chemical shift were observed upon the binding of the
      neurotensin(8-13) to the receptor. Most importantly significant shifts were
      observed in both the carboxy terminus and tyrosine side chain of the
      neurotensin(8-13), suggesting that these sites are important in the interaction
      of the neurotensin with the agonist-binding site on the neurotensin receptor.
      Conversely, no perturbations were observed for the carbon-13 sites within the
      guanidinium groups of the arginine side chains, indicating little interaction
      with the receptor-binding site, or a shielding of the local environment by the
      surrounding nitrogen atoms. These NMR observations lend further support to
      previous structure-activity studies, site-directed mutagenesis and modelling
      studies of the agonist-binding site of the neurotensin receptor, from which the
      same specific residues for which NMR perturbations were observed are important
      for neurotensin receptor activation by neurotensin.

PMID- 11997029
TI  - The presence of 4-hydroxyphenylacetic acid in human saliva and the possibility of
      its nitration by salivary nitrite in the stomach.
AB  - Human saliva contained 4-hydroxyphenylacetic acid (HPA) (2-10 microM) and nitrite
      (60-300 microM). HPA was nitrated to 4-hydroxy-3-nitrophenylacetic acid (NO2HPA)
      when HPA and sodium nitrite were mixed at pH 1.0. NO2HPA was also formed when
      saliva was incubated under acidic conditions. These results suggest that salivary
      HPA is nitrated to NO2HPA when saliva is swallowed into the stomach.

PMID- 11997030
TI  - Most immunoglobulin heavy chain switch mu rearrangements in B-cell chronic
      lymphocytic leukemia are internal deletions.
AB  - We investigated 38 cases of B-cell chronic lymphocytic leukemia (B-CLL) for the
      presence of non-productive rearrangements in the S(mu) regions and defined for
      the first time the molecular nature of these rearrangements. Southern blot
      analysis revealed S(mu) region rearrangements in 13 cases (34%) and polymerase
      chain reactions (PCRs) indicated that these rearrangements consisted of internal
      deletions of the S(mu) region. Long-distance PCRs localized the S(mu) deletions
      in the V(H)DJ(H) rearranged allele in most cases. We investigated if S(mu)
      deletions were related to V(H) somatic mutations that, together with isotype
      switch recombination, are indicative of the B-cell maturation stage. No
      significant correlation between the presence of S(mu) deletions and V(H) somatic
      mutations was found, indicating that the two processes are independent in B-CLL.
      Moreover no significant correlation between S(mu) deletions and prognosis was
      observed. Having shown that S(mu) internal deletions are not chromosome
      translocations rules out their involvement in the onset of malignancy, while
      their localization in the V(H)DJ(H) rearranged alleles suggests a possible role
      in the stabilization of the isotype of the expressed immunoglobulin.

PMID- 11997031
TI  - Isolation and characterization of circulating fragments of the insulin-like
      growth factor binding protein-3.
AB  - Proteolysis of insulin-like growth factor binding protein-3 (IGFBP-3), the major
      carrier of IGFs in the circulation, is an essential mechanism to regulate IGF
      bioavailability. To analyze naturally occurring IGFBP-3 fragments a peptide
      library established from human hemofiltrate was screened. Three IGFBP-3 fragments
      were detected with apparent molecular masses of 34, 16, and 11 kDa. Mass
      spectrometric and sequence analysis identified the 16 and 11 kDa peptides as
      glycosylated and non-glycosylated N-terminal fragments spanning residues Gly1
      Ala98 of IGFBP-3. Both the circulating forms and those secreted from IGFBP-3(1
      98) overexpressing cells bound IGF. Additionally, two smaller fragments (IGFBP
      3(139-157) and IGFBP-3(139-159)) were identified in the hemofiltrate. The data
      indicate that proteolysis of circulating IGFBP-3 occurs in the variable domain at
      residues alanine 98, phenylalanine 138, glutamine 157, and tyrosine 159.

PMID- 11997032
TI  - Rac1 prevents cisplatin-induced apoptosis through down-regulation of p38
      activation in NIH3T3 cells.
AB  - In this study, the role of V12-Rac1 in the cisplatin-induced apoptosis was
      investigated. Cisplatin-induced apoptosis is associated with cytochrome c
      release, which can be inhibited by V12-Rac1 expression. The analysis of mitogen
      activated protein kinase activity indicated that V12-Rac1 expression led to a
      decrease in p38 activity after exposure to cisplatin but not c-jun N-terminal
      kinase and extracellular signal-regulated kinase. Using pharmacological
      inhibitors, it was found that only p38 is a critical mediator in the cisplatin
      induced apoptosis of NIH3T3 cells. This suggests that V12-Rac1 can stimulate the
      anti-apoptotic signaling pathway in response to cisplatin, and that decreased p38
      activity caused by V12-Rac1 expression in cisplatin-treated NIH3T3 cells is
      crucial for V12-Rac1-dependent cell survival.

PMID- 11997033
TI  - Spontaneous lipid vesicle fusion with electropermeabilized cells.
AB  - Fusion is obtained between electropermeabilized mammalian cells and intact large
      unilamellar lipid vesicles. This is monitored by a fluorescence assay. Prepulse
      contact is obtained by Ca2+ when negatively charged lipids are present in the
      liposomes. The mixing of the liposome content in the cell cytoplasm is observed
      under conditions preserving cell viability. Electric conditions are such that
      free liposomes are not affected by the external field. Therefore destabilization
      of only one of the two membranes of the partners is sufficient for fusion. The
      comparison between the efficiency of dye delivery for different liposome
      preparations (multilamellar vesicles, large unilamellar vesicles, small
      unilamellar vesicles) is indicative that more metastable liposomes are more
      fusable with electropulsated cells. This observation is discussed within the
      framework of the recent hypothesis that occurrence of a contact induced
      electrostatic destabilization of the plasma membrane is a key step in the
      exocytosis process.

PMID- 11997034
TI  - Leucyl-tRNA synthetase from the extreme thermophile Aquifex aeolicus has a
      heterodimeric quaternary structure.
AB  - Class I aminoacyl-tRNA synthetases have been thought to be single polypeptide
      enzymes. However, the complete genome sequence of a hyper thermophile Aquifex
      aeolicus suggests that the gene for leucyl-tRNA synthetases (LeuRS) is probably
      split into two pieces (leuS and leuS'). In this research, each gene was
      separately cloned and overexpressed in Escherichia coli and the protein products
      were examined for LeuRS activity. Leucylation activity was detected only when
      both gene products coexisted. Gel filtration analysis showed that the active form
      of A. aeolicus LeuRS has a heterodimeric (alpha/beta type) quaternary structure
      that is unique among class I aminoacyl-tRNA synthetases.

PMID- 11997035
TI  - Nucleotide excision repair by extracts of human fetal hepatocytes.
AB  - Human hepatocytes are particularly exposed to genotoxins, and nucleotide excision
      repair (NER) in these cells is essential for the maintenance of genome integrity.
      To characterize NER under conditions that closely resemble the pathway in vivo,
      we report the preparation and use of primary human fetal liver extracts to define
      the repair of a 1,3-intrastrand d(GpTpG)-cisplatin DNA lesion. Endonucleolytic
      cleavage at unique sites on either side of the adduct occurs at similar positions
      to the dominant NER incisions that have been reported for HeLa extracts. However,
      incisions effected by primary hepatocyte extracts are more precise as no
      secondary cleavage sites are detected 5' and 3' to the cisplatin lesion.

PMID- 11997036
TI  - In situ visualization of caspase-1-like activity associated with promotion of
      hippocampal cell death.
AB  - To clarify the function of caspase-1-like proteases in neuronal cell death, it is
      important to be able to detect the activity in living organs by microscopic
      visualization. In the present study, we synthesized a novel fluorescent substrate
      sensitive to the caspase-1-like activity, which is easily introduced into cells
      constituting living organs by extracellular application. As a result, the
      substrate was shown to be useful in imaging the caspase-1-like activity in rat
      hippocampal slice cultures. After induction of cell death with glutamate, a
      significant increase in the activity was observed, especially in the pyramidal
      cells, suggesting the association of the activity with promotion of cell death.

PMID- 11997037
TI  - Prostaglandin E2 reinforces the activation of Ras signal pathway in lung
      adenocarcinoma cells via EP3.
AB  - Prostaglandin E2 (PGE2)-dependent effects on various cell responses are regulated
      by respective PGE2 receptors (EP1, EP2, EP3, EP4) expressing in target cells.
      Alveolar type II cell (a main progenitor cell of lung adenocarcinoma) expressed
      only EP4, while human lung adenocarcinoma cells (A549) expressed EP3 as well as
      EP4. An antagonistic effect of EP3 against EP4 through the modulation of cyclic
      AMP level is required for PGE2-mediated activation of Ras signal pathway in A549
      cells. These results suggest that the expression of EP3 may be a critical factor
      for the PGE2-mediated activation of Ras signal pathway in A549 cells.

PMID- 11997038
TI  - Butyric acid increases invasiveness of HL-60 leukemia cells: role of reactive
      oxygen species.
AB  - Butyric acid (BA) induces differentiation of human leukemia, including HL-60
      cells. By using a fluorescent probe, we showed that reactive oxygen species (ROS)
      were generated in BA-treated cells. BA-induced differentiation was accompanied
      with an increased secretion of pro-matrix metalloproteinase (MMP)-9. Both
      phenomena were inhibited by antioxidants. Tissue inhibitors of MMP (TIMP)-1 and 
      2 secretion were increased by BA, but differently affected by antioxidants. By
      contrast, BA did not affect MMP-9 mRNA, and decreased TIMP-1 and TIMP-2 mRNA
      levels. In addition, migratory and invasive properties of HL-60 cells were
      enhanced by BA, but differently affected by antioxidants. Altogether, these
      results indicate that ROS are messengers of BA-induced differentiation and
      increased invasiveness.

PMID- 11997039
TI  - cDNA cloning and characterization of tobacco ABC transporter: NtPDR1 is a novel
      elicitor-responsive gene.
AB  - We isolated an INF1 elicitin-inducible cDNA encoding a pleiotropic drug
      resistance (PDR)-type ATP-binding cassette (ABC) transporter homolog (NtPDR1) in
      suspension-cultured tobacco Bright Yellow-2 (BY-2) cells by application of
      differential display PCR. The NtPDR1 (Nicotiana tabacum PDR protein 1) gene also
      encodes a 162 kDa protein that includes two putative hydrophilic domains
      containing the ABC signature motif and two putative hydrophobic domains.
      Expression of the NtPDR1 gene was rapidly and strongly activated by treatment of
      BY-2 cells with INF1 elicitin. Further, treatment of BY-2 cells with flagellin, a
      bacterial proteinaceous hypersensitive reaction elicitor, or yeast extract, a
      general elicitor, also induced NtPDR1 gene expression. These results indicate
      that NtPDR1 may be involved in the general defense response in tobacco. This is
      the first report that microbial elicitors induce the expression of a plant ABC
      transporter gene.

PMID- 11997040
TI  - Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression
      by hepatitis B virus X protein and hepatitis C virus core protein.
AB  - Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is common
      and is associated with a more severe liver disease and increased frequency in the
      development of hepatocellular carcinoma (HCC). Here, we demonstrated that HBV X
      protein (HBx) and HCV core protein additively repress the universal cyclin
      dependent kinase inhibitor p21 gene at the transcription level. The transforming
      growth factor-beta responsive element and Sp1 site of the p21 promoter were
      responsible for the effect of HCV core and HBx, respectively. Furthermore, cell
      growth was additively stimulated by them, suggesting that additive repression of
      the p21 might be important to understand the cooperative development of HCC by
      HBV and HCV.

PMID- 11997041
TI  - PspE (phage-shock protein E) of Escherichia coli is a rhodanese.
AB  - The psp (phage-shock protein) operon of Escherichia coli is induced when the
      bacteria are infected by filamentous phage and under several other stress
      conditions. The physiological role of the individual Psp proteins is still not
      known. We demonstrate here that the last gene of the operon, pspE, encodes a
      thiosulfate:cyanide sulfurtransferase (EC 2.8.1.1; rhodanese). Kinetic analysis
      revealed that catalysis occurs via a double displacement mechanism as described
      for other rhodaneses. The K(m)s for SSO3(2-) and CN- were 4.6 and 27 mM,
      respectively.

PMID- 11997042
TI  - Partially structured state of the functional VH domain of the mouse anti-ferritin
      antibody F11.
AB  - An antibody combining site generally involves the two variable domains, VH from
      the heavy and VL from the light chain. We expressed the individual VH domain of
      the mouse anti-human ferritin monoclonal antibody F11. The loss of affinity was
      not dramatic (K(a)=4.0x10(7) M(-1) versus 8.6x10(8) M(-1) for the parent
      antibody) and comparable to that previously observed for other VHs. However, the
      functional VH domain adopted a partially structured state with a significant
      amount of distorted secondary and compact yet greatly destabilized tertiary
      structures, as demonstrated by spectroscopic and calorimetric probes. These data
      provide the first description for a functional antibody domain that meets all the
      criteria of a partially structured state.

PMID- 11997043
TI  - Nucleoside triphosphate pentose ring impact on CFTR gating and hydrolysis.
AB  - Alterations in the pentose ring of ATP have a major impact on cystic fibrosis
      transmembrane conductance regulator (CFTR) function. Both 2'- and 3'-deoxy-ATP
      (dATP) accelerate ion channel openings and stabilize open channel structure
      better than ATP. Purified wild-type CFTR hydrolyzes dATP. The apparent first
      order rate constants for hydrolysis at low substrate concentration are the same
      for dATP and ATP. This suggests that product release and/or relaxation of the
      enzyme structure to the initial ligand free state is the rate-limiting step in
      the CFTR hydrolytic cycle. Circumvention of the normal requirement for protein
      kinase A phosphorylation of the R-domain for channel activation implies that the
      impact of the deoxyribonucleotide interaction with the nucleotide binding domains
      is transmitted to the channel-forming elements of the protein more readily than
      that of the ribonucleotide.

PMID- 11997044
TI  - Amino acid residues 268-276 of the erythropoietin receptor contain an endocytosis
      motif and are required for erythropoietin-mediated proliferation.
AB  - Erythropoietin (EPO) promotes viability, proliferation and differentiation of
      mammalian erythroid progenitor cells via its specific cell surface receptor (EPO
      R). We have previously shown that truncated EPO-Rs containing 267 amino acids or
      less were defective in internalization of (125)I-EPO, whereas internalization via
      a receptor derivative containing 276 amino acids was unaffected, thus directing
      focus to the nine amino acid residues FEGLFTTHK at positions 268-276 [Levin,
      Cohen, Supino, Yoshimura, Watowich, Neumann, FEBS Lett. 427 (1998) 164-170].
      Here, a panel of EPO-R mutants was generated to determine the role of these
      residues in EPO endocytosis, down regulation of cell surface receptors and EPO
      mediated signaling. While linking amino acid residues 268-276 to a truncated EPO
      R (Delta+9 EPO-R) conferred both ligand uptake and ligand-independent down
      regulation of the respective receptor from the cell surface, Phe 272 was crucial
      for EPO endocytosis but not for ligand-independent down regulation. Additional
      receptor motifs probably play a role in EPO endocytosis and receptor down
      regulation, as these processes were not adversely impaired in Delta268-276 EPO-R.
      A central role of residues 268-276, in particular Phe, was demonstrated by the
      inability of Delta268-276 and F268,272A EPO-Rs to support EPO-mediated signal
      transduction.

PMID- 11997045
TI  - Extracellular signal-regulated kinases control expression of G protein-coupled
      receptor kinase 2 (GRK2).
AB  - G protein-coupled receptor kinase 2 (GRK2) phosphorylates G protein-coupled
      receptors resulting in uncoupling from G proteins. Receptors modulate GRK2
      expression, however the mechanistic basis for this effect is largely unknown.
      Here we report a novel mechanism by which receptors use the extracellular signal
      regulated kinase (ERK) cascade to regulate GRK2 cellular levels. ERK activation
      by receptor stimulation elevated endogenous GRK2 while antagonist treatment
      decreased cellular GRK2. Activating ERK by overexpressing constitutive active MEK
      1 or Ras elevated GRK2 protein levels while blocking ERK using PD98059 or
      dominant negative Ras abolished this effect. These data suggest ERK is a critical
      regulator of GRK2 levels.

PMID- 11997046
TI  - Spiral mechanisms are required to account for summation of complex motion
      components.
AB  - Stimuli from one family of complex motions are defined by their spiral pitch,
      where cardinal axes represent signed expansion and rotation. Intermediate spirals
      are represented by intermediate pitches. It is well established that vision
      contains mechanisms that sum over space and direction to detect these stimuli
      (Morrone et al., Nature 376 (1995) 507) and one possibility is that four cardinal
      mechanisms encode the entire family. We extended earlier work (Meese & Harris,
      Vision Research 41 (2001) 1901) using subthreshold summation of random dot
      kinematograms and a two-interval forced choice technique to investigate this
      possibility. In our main experiments, the spiral pitch of one component was fixed
      and that of another was varied in steps of 15 degrees relative to the first.
      Regardless of whether the fixed component was aligned with cardinal axes or an
      intermediate spiral, summation to-coherence-threshold between the two components
      declined as a function of their difference in spiral pitch. Similar experiments
      showed that none of the following were critical design features or stimulus
      parameters for our results: superposition of signal dots, limited life-time dots,
      the presence of speed gradients, stimulus size or the number of dots. A simplex
      algorithm was used to fit models containing mechanisms spaced at a pitch of
      either 90 degrees (cardinal model) or 45 degrees (cardinal+model) and combined
      using a fourth-root summation rule. For both models, direction half-bandwidth was
      equated for all mechanisms and was the only free parameter. Only the
      cardinal+model could account for the full set of results. We conclude that the
      detection of complex motion in human vision requires both cardinal and spiral
      mechanisms with a half-bandwidth of approximately 46 degrees.

PMID- 11997047
TI  - GABAc feedback pathway modulates the amplitude and kinetics of ERG b-wave in a
      mammalian retina in vivo.
AB  - The electroretinogram b-wave is generally believed to reflect mainly light
      induced activity of ON-center bipolar cells and Muller cells. Recently, there is
      increasing evidence that third-order retinal neurons can also contribute
      significantly to the b-wave. In a previous study (Vis. Res. 40 (2000) 579) we
      proposed that the GABAc feedback from amacrine cells to bipolar cells can affect
      both the amplitude and kinetics of the b-wave. Here we show that blocking this
      feedback has profound effects on b-wave amplitude and kinetics. These results
      demonstrate that feedback to bipolar cells is an important mechanism through
      which amacrine cells contribute to b-wave generation. Our results also provide
      functional evidence that the feedback may be involved in temporal processing in
      the mammalian retina.

PMID- 11997048
TI  - The Stiles-Crawford effect and subjective measurement of aberrations.
AB  - We considered the influence that the Stiles-Crawford effect (SCE) has on the
      measurement of subjective monochromatic and transverse aberration measurements.
      The SCE was measured with a two channel Maxwellian-viewing system. Transverse
      aberrations were measured using a vernier alignment technique in three subjects,
      with the natural SCE operating, with the SCE neutralised by filters optically
      conjugate with the eye's pupil, and for one subject with filters that shifted the
      SCE by more than 2 mm. As pupil diameter increased from 1 to 5 mm diameter,
      without the filters the slope of the transverse aberration versus position in the
      pupil decreased, e.g. for chromatic aberration this decreased by approximately
      90%. The filters had little influence on transverse aberration. The results
      indicate that subjects do not use the centroid of the image of a blurred line
      target for alignment, but may rely very much on other cues.

PMID- 11997049
TI  - Multi-coloured stereograms unveil two binocular colour mechanisms in human
      vision.
AB  - Two different colours, one presented to one eye and the other presented to the
      other eye, often create the impression of a third colour. This percept is known
      as binocular colour mixture. Here we use coloured stereograms to study binocular
      colour appearance. Vivid pastel colours are induced in monocular, achromatic
      patches, if these are placed in stereograms whose left and right images differ in
      colour. The build-up of the colours is slow and takes tens of seconds or even
      minutes in certain individuals. The induced colours remain visible during
      monocular viewing of the patch and decay gradually. The same colours are induced
      irrespective of whether the patches are placed in fusible or rivalrous
      stereograms. We show that these colour effects cannot be induced by monocular
      colour mechanisms, either alone or in combination with binocular colour mixing.
      We suggest that the colours are induced by a binocular feedback mechanism, which
      reduces colour differences between the colour appearances of two monocular
      images. Induced colours are not observed if the achromatic patches are binocular.
      However, induced colours are apparent if one switches to monocular viewing after
      prolonged binocular viewing of the binocular patches. This aftereffect suggests
      that binocular colour induction acts on the monocular representations of
      binocular images. We suggest that during binocular viewing the fast process of
      binocular colour mixing masks the changes in colour appearance produced by the
      much slower process of binocular colour induction.

PMID- 11997050
TI  - Adaptation and gain pool summation: alternative models and masking data.
AB  - Foley [J. Opt. Soc. Am. A 11 (1994) 1710] has proposed an influential
      psychophysical model of masking in which mask components in a contrast gain pool
      are raised to an exponent before summation and divisive inhibition. We tested
      this summation rule in experiments in which contrast detection thresholds were
      measured for a vertical 1 c/deg (or 2 c/deg) sine-wave component in the presence
      of a 3 c/deg (or 6 c/deg) mask that had either a single component oriented at -45
      degrees or a pair of components oriented at +/-45 degrees. Contrary to the
      predictions of Foley's model 3, we found that for masks of moderate contrast and
      above, threshold elevation was predicted by linear summation of the mask
      components in the inhibitory stage of the contrast gain pool. We built this
      feature into two new models, referred to as the early adaptation model and the
      hybrid model. In the early adaptation model, contrast adaptation controls a
      threshold-like nonlinearity on the output of otherwise linear pathways that
      provide the excitatory and inhibitory inputs to a gain control stage. The hybrid
      model involves nonlinear and nonadaptable routes to excitatory and inhibitory
      stages as well as an adaptable linear route. With only six free parameters, both
      models provide excellent fits to the masking and adaptation data of Foley and
      Chen [Vision Res. 37 (1997) 2779] but unlike Foley and Chen's model, are able to
      do so with only one adaptation parameter. However, only the hybrid model is able
      to capture the features of Foley's (1994) pedestal plus orthogonal fixed mask
      data. We conclude that (1) linear summation of inhibitory components is a feature
      of contrast masking, and (2) that the main aftereffect of spatial adaptation on
      contrast increment thresholds can be assigned to a single site.

PMID- 11997051
TI  - Monocular alignment in different depth planes.
AB  - We examined (a) whether vertical lines at different physical horizontal positions
      in the same eye can appear to be aligned, and (b), if so, whether the difference
      between the horizontal positions of the aligned vertical lines can vary with the
      perceived depth between them. In two experiments, each of two vertical monocular
      lines was presented (in its respective rectangular area) in one field of a random
      dot stereopair with binocular disparity. In Experiment 1, 15 observers were asked
      to align a line in an upper area with a line in a lower area. The results
      indicated that when the lines appeared aligned, their horizontal physical
      positions could differ and the direction of the difference coincided with the
      type of disparity of the rectangular areas; this is not consistent with the law
      of the visual direction of monocular stimuli. In Experiment 2, 11 observers were
      asked to report relative depth between the two lines and to align them. The
      results indicated that the difference of the horizontal position did not covary
      with their perceived relative depth, suggesting that the visual direction and
      perceived depth of the monocular line are mediated via different mechanisms.

PMID- 11997052
TI  - Isolation of stimulus characteristics contributing to Weber's law for position.
AB  - To examine the independent contribution of various stimulus characteristics to
      positional judgements, we measured vernier alignment performance for three types
      of Gabor stimuli. In one, only the contrast envelope of the upper and lower
      stimulus elements was offset, with the luminance-modulated carrier grating
      remaining in alignment. In the second, only the carrier grating was offset. In
      the third, both carrier and envelope were offset together. Performance was
      examined over a range of element separations. When both cues are available,
      thresholds for small separations are dominated by carrier offset information and
      are inversely proportional to carrier frequency. At large separations, thresholds
      are governed by the spatial scale characteristics of the envelope. For broad-band
      stimuli such as lines, bars or dots typically used for vernier acuity, their
      higher frequency content can be used when separations are small, but as
      separation increases a smooth transition between the scales that determine
      threshold results in the continuum known as Weber's law for position. That is,
      with increasing separation, larger scales must be used, and thresholds increase
      in direct proportion to 1/frequency.

PMID- 11997053
TI  - Effect of eccentricity on luminance-pedestal flicker thresholds.
AB  - We investigated the effect that spatially coincident luminance increments
      (luminance pedestals) have on flicker thresholds at several eccentricities and
      target sizes. Luminance pedestals elevated flicker amplitude-thresholds more when
      stimuli were presented eccentrically, both at low (4 Hz) and high (20 Hz)
      temporal frequencies. Altering the size of the eccentric stimulus failed to
      equate central and eccentric thresholds at all pedestal amplitudes. Comparisons
      with flicker thresholds at various background luminances suggests that the
      increase in luminance-pedestal flicker thresholds peripherally is due to
      increased suppressive rod-cone interactions, increased effectiveness of luminous
      contrast on edge-sensitive flicker mechanisms, as well as increased gain in the
      light adaptation response.

PMID- 11997054
TI  - The role of the cyclopean eye in vision: sometimes inappropriate, always
      irrelevant.
AB  - During binocular fixation, the eyes usually point in different directions, and
      yet, each object is judged to lie in a single direction. It is commonly believed
      that a particular location in the head serves as the origin for such directional
      judgments. This location is known as the cyclopean eye. We argue here that
      observers can judge visually perceived directions from angular information alone,
      and do not require positional information supplied by a cyclopean eye. We show
      that experimental findings reported as evidence for the cyclopean concept can
      also be explained solely by angular information without the need for a cyclopean
      eye. Recent findings concerning binocular shape perception and the cyclopean
      illusion demonstrate that binocular perception is incompatible with vision from a
      single vantage point. The concept of the cyclopean eye is sometimes inappropriate
      and always irrelevant as far as vision is concerned.

PMID- 11997055
TI  - The role of spatial frequency channels in letter identification.
AB  - How we see is today explained by physical optics and retinal transduction,
      followed by feature detection, in the cortex, by a bank of parallel independent
      spatial-frequency-selective channels. It is assumed that the observer uses
      whichever channels are best for the task at hand. Our current results demand a
      revision of this framework: Observers are not free to choose which channels they
      use. We used critical-band masking to characterize the channels mediating
      identification of broadband signals: letters in a wide range of fonts (Sloan,
      Bookman, Kunstler, Yung), alphabets (Roman and Chinese), and sizes (0.1-55
      degrees ). We also tested sinewave and squarewave gratings. Masking always
      revealed a single channel, 1.6+/-0.7 octaves wide, with a center frequency that
      depends on letter size and alphabet. We define an alphabet's stroke frequency as
      the average number of lines crossed by a slice through a letter, divided by the
      letter width. For sharp-edged (i.e. broadband) signals, we find that stroke
      frequency completely determines channel frequency, independent of alphabet, font,
      and size. Moreover, even though observers have multiple channels, they always use
      the same channel for the same signals, even after hundreds of trials, regardless
      of whether the noise is low-pass, high-pass, or all-pass. This shows that
      observers identify letters through a single channel that is selected bottom-up,
      by the signal, not top-down by the observer. We thought shape would be processed
      similarly at all sizes. Bandlimited signals conform more to this expectation than
      do broadband signals. Here, we characterize processing by channel frequency. For
      sinewave gratings, as expected, channel frequency equals sinewave frequency
      f(channel)=f. For bandpass-filtered letters, channel frequency is proportional to
      center frequency f(channel) proportional, variantf(center) (log-log slope 1) when
      size is varied and the band (c/letter) is fixed, but channel frequency is less
      than proportional to center frequency f(channel) proportional,
      variantf(center)(2/3) (log-log slope 2/3) when the band is varied and size is
      fixed. Finally, our main result, for sharp-edged (i.e. broadband) letters and
      squarewaves, channel frequency depends solely on stroke frequency,
      f(channel)/10c/deg=(2/3), with a log-log slope of 2/3. Thus, large letters (and
      coarse squarewaves) are identified by their edges; small letters (and fine
      squarewaves) are identified by their gross strokes.

PMID- 11997056
TI  - Changes in cyclotorsion and vertical eye alignment during prolonged monocular
      occlusion.
AB  - When binocular vision is prevented with monocular occlusion, the two eyes assume
      a position of rest related to the combination of underlying tonic innervation of
      the oculomotor system, cross-coupled accommodative-vergence input and vergence
      responses to perceptual cues for spatial location relative to the head. When the
      latter two are controlled, the covered eye has been shown in the majority of
      subjects to turn outward (exophoria) and upward (hyperphoria) after prolonged
      monocular occlusion. The present study investigates the change in torsional eye
      alignment and its relation to vertical eye alignment after eight hours of
      monocular occlusion. The results revealed an excyclophoria during occlusion in
      four out of five subjects. The patched eye also became elevated in two subjects
      and depressed in two others. Thus, during prolonged monocular occlusion, the
      relative directions of cyclophoria and vertical phoria appear to be independent.
      In addition, there were non-concomitant changes in vertical phoria with
      horizontal gaze, toward a state where the adducted eye was elevated relative to
      the abducted eye. Simulations with Orbit(TM) suggest that these non-concomitant
      changes in vertical phoria with a concomitant excyclophoria may be based upon
      orbital mechanics. Excyclophoria appears to be the baseline state of binocular
      alignment.

PMID- 11997057
TI  - Deficits of motion transparency perception in adult developmental dyslexics with
      normal unidirectional motion sensitivity.
AB  - We assessed motion integration ability in seven adult developmental dyslexics
      using unidirectional and bidirectional (transparent) random dot kinematograms
      (RDKs) that varied in the number of frames. All adult dyslexics performed as well
      as normally reading age-matched controls with unidirectional RDKs, regardless of
      frame number. However, using orthogonal motion transparent stimuli, deficits were
      obvious in six dyslexics and depended on frame number. Whereas controls needed on
      average only 4.4 frames (144 ms) to identify both directions correctly on 75% of
      presentations, dyslexics needed on average 14.6 frames (483 ms) to achieve this
      level of performance. Even though a unidirectional motion task failed to reveal
      processing abnormalities in adult dyslexics, the motion transparency task was
      effective at revealing significant perceptual dysfunction, suggesting that
      performance on this task is a better psychophysical indicator of visual motion
      deficits in dyslexia. This finding provides little support for the magnocellular
      deficit hypothesis and, rather, points to abnormality within dorsal extrastriate
      cortical areas that subserve the integration and segmentation of complex motion
      signals.

PMID- 11997058
TI  - Using a single test to measure human contrast sensitivity from early childhood to
      maturity.
AB  - Despite the emerging scientific and clinical importance of measuring human
      contrast sensitivity (CS), developmental data are sparse, especially those
      obtained with a single methodology. We used a new, time-efficient, psychophysical
      card procedure to evaluate binocular CS in groups of 20 4- to 9-yr-olds and 10
      adults. Combined with data from infants and toddlers obtained previously with the
      same method, our results show that CS is adult-like by 9 years of age. However,
      the pattern of development is asymmetrical across spatial frequency (SF):
      Sensitivity at high SF (which is very poor near birth) shows dramatic improvement
      over the first three years, but sensitivity at low SF shows much more gradual
      development, a result which may be explained by differences in the maturation of
      the underlying neural SF channels. Also notable is that the method shows clinical
      potential due to its relative speed, ease of use, and consistent results across
      such a broad age range.

PMID- 11997059
TI  - Comments on: variation in vernier acuity with age.

PMID- 11997060
TI  - Early intervention with immunomodulatory agents in the treatment of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a lifelong neurologic disease leading to moderate or
      severe disability in the majority of affected patients. Studies of the natural
      history of MS suggest that 90% of patients with relapsing-remitting MS eventually
      develop secondary progressive (SP) disease. Magnetic resonance imaging (MRI)
      studies have consistently shown a high frequency of new T2 lesions and new
      gadolinium enhancing lesions even in the absence of clinical relapse. Lesion
      burden on T2 MRI increases by 5% to 10% per year and both axonal transection and
      cerebral atrophy are present at the earliest stages of RR MS. A wealth of
      evidence suggests that MS is a disease process that is continuously active, and
      that irreversible damage occurs early in the disease. Despite knowledge of the
      natural history and the availability of treatments that reduce relapse rates,
      decrease the accumulation of disability, and decrease surrogate measures of
      disease activity, only 60% of eligible patients have been treated with
      immunomodulating agents. This paper reviews the available evidence suggesting
      that immunomodulatory therapy modifies the natural history of MS and presents an
      argument for early intervention in the treatment of MS.

PMID- 11997061
TI  - Caspase-1 expression in multiple sclerosis plaques and cultured glial cells.
AB  - Caspase-1 is responsible for processing inflammatory cytokines and is associated
      with the induction of apoptosis. Using RT-PCR, we found that caspase-1 mRNA
      transcripts from frozen brain extracts were significantly elevated in multiple
      sclerosis (MS) compared to controls. Immunohistochemical staining using a
      specific antiserum confirmed the marked up regulation of caspase-1 within acute
      and chronic MS plaques, while little staining was seen in control brains. In
      addition to the expected caspase-1 expression in microglia and infiltrating
      perivascular mononuclear cells, we found that cytoplasmic caspase-1 expression
      was sharply increased in the resident oligodendrocytes of MS lesions. The TUNEL
      reaction for fragmented DNA co-localized over an occasional caspase-1-expressing
      cell and large numbers of caspase-1-positive "corpses" were observed within
      phagocytic macrophages of an acute evolving MS lesion. Studies using an
      immortalized human oligodendroglial hybrid cell line exposed to cytokine
      challenge showed that death induction was blocked by the caspase-1-like inhibitor
      Z-YVAD-fmk, while the caspase-3-like inhibitor Z-DEVD-fmk was less effective.
      Cellular levels of procaspase-1 were reduced compared to controls in
      oligodendroglia induced to die by cytokine challenge, as judged by Western
      immunoblotting. Our results suggest that caspase-1 may play a role in the
      inflammatory and apoptotic processes associated with MS pathogenesis.

PMID- 11997062
TI  - Persistent hypertension does not alter the cerebral blood flow and glucose
      utilization in young-adult Dahl salt-sensitive rats.
AB  - The Dahl- Iwai salt-sensitive (DS) rat develops hypertension due to a high-salt
      diet without any structural alterations of the brain arteries and arterioles. We
      investigated the effect of persistent hypertension on the regional cerebral blood
      flow (rCBF) and regional cerebral glucose utilization (rCGU) in the DS rats. The
      rats were fed either a high-salt diet (HSD; 8% NaCl, n = 5) or a low-salt diet
      (LSD; 0.3% NaCl, n = 6) from 8 to 16 weeks of age, and the HSD group developed
      hypertension lasting for 1 month. At 16 weeks of age, the rCBF was measured in
      the sensorimotor and visual cortices using the hydrogen clearance method, and the
      rCGU was measured in 26 different brain structures using the [(14)C]deoxyglucose
      method. The mean arterial pressure was significantly higher in the HSD group
      (168+/-7 mm Hg) than in the LSD group (139+/-3 mm Hg) (P < 0.01). The mean rCBF
      and the rCGU values tended to be lower in the HSD group than in the LSD group;
      however, there were no statistically significant differences except for the
      reduced rCGU value in the nucleus accumbens. These results suggest that
      hypertension itself does not alter either the rCBF or the rCGU in young-adult DS
      rats. This indicates that the functional / structural changes of the cerebral
      arteries and arterioles that are associated with hypertension appear to be
      responsible for altered rCBF and rCGU in other animal models of hypertension.

PMID- 11997063
TI  - Sp1 and the ets-related transcription factor complex GABP alpha/beta functionally
      cooperate to activate the utrophin promoter.
AB  - Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by the
      absence of dystrophin. Utrophin is the autosomal homolog of dystrophin and
      capable of compensating for the absence of dystrophin, when overexpressed. In
      skeletal muscle, utrophin plays an important role in the formation of
      neuromuscular junctions. This selective enrichment occurs, in part by
      transcriptional regulation of the utrophin gene at the sub-synaptic nuclei in
      muscle. Utrophin's complex transcriptional regulation is not yet fully
      understood, however, GABP alpha / beta has recently been shown to bind the N box
      and activate the utrophin promoter in response to heregulin. In this study, we
      show that the transcription factor Sp1 binds and activates the utrophin promoter
      in Drosophila S2 cells as well as define a Sp1 response element. We demonstrate
      that heregulin treatment of cultured muscle cells activates the ERK pathway and
      phosphorylates serine residue(s) in the consensus ERK recognition site of Sp1.
      Finally, Sp1 is shown to functionally cooperate with GABP alpha / beta and cause
      a 58-fold increase of de novo utrophin promoter transcription. Taken together,
      these findings help define mechanisms used for transcriptional regulation of
      utrophin expression as well as identify new targets for achieving potentially
      therapeutic upregulation of utrophin in DMD.

PMID- 11997064
TI  - Different mechanism of vocal cord paralysis between spinocerebellar ataxia (SCA 1
      and SCA 3) and multiple system atrophy.
AB  - While multiple system atrophy (MSA) is frequently associated with vocal cord
      paralysis (VCP) causing severe respiratory failure, it is still unknown whether
      hereditary types of spinocerebellar degeneration develop similar laryngeal
      paralysis. We analyzed the laryngeal function from the viewpoints of fiberoptic
      laryngoscopy and laryngeal myopathology and then attempted to clarify the
      difference of the mechanism of VCP among the patients with spinocerebellar ataxia
      type 1 (SCA 1), type 3 (SCA 3), and MSA. Seven patients with SCA 1, nineteen with
      SCA 3, and eleven with MSA were studied. Vocal cord movement was analyzed by
      fiberoptic laryngoscopy during wakefulness and diazepam-induced sleep (sleep load
      test). Paraffin-embedded sections or cryosections of the intrinsic laryngeal
      muscles from five autopsied cases (one with SCA 1 and four with SCA 3) were
      histologically examined. VCP was found in two of the seven SCA 1 patients (29%),
      three of the nineteen SCA 3 patients (16%), and in nine of the eleven MSA
      patients (82%). VCP observed in SCA 1 and SCA 3 was various in the severity and
      showed no exacerbation on sleep load test in all of the eight patients but one
      SCA 3 patient. In this patient, the findings of fiberoptic laryngoscopy were
      quite similar to those found in MSA. All the intrinsic laryngeal muscles
      including cricothyroid (CT), interarytenoid (IA), and posterior cricoarytenoid
      (PCA) muscles showed neurogenic atrophy in one autopsied SCA 1 and four SCA 3
      patients. Our conclusion is that VCP in SCA 1 and SCA 3 contrasts with that in
      MSA in its occurrence, response to the sleep load test, and the distribution of
      the neurogenic abnormalities among the intrinsic laryngeal muscles.

PMID- 11997065
TI  - White matter T(1) relaxation time histograms and cerebral atrophy in multiple
      sclerosis.
AB  - T(1) relaxation time (T(1)) provides a quantitative magnetic resonance imaging
      (MRI) parameter for evaluating tissue damage in the brain. We aimed to measure
      T(1) in the white matter of patients with multiple sclerosis (MS) and study
      relationships with cerebral atrophy, T(2) lesion load and clinical parameters.
      Twenty-six patients with relapsing-remitting MS and sixteen healthy controls were
      scanned with dual-echo T(2)-weighted, 3-dimensional (3-D) magnetization-prepared
      rapid acquisition gradient echo and whole brain, multi-slice inversion recovery
      (IR) sequences. White matter masks were defined on axial T(1) map slices using
      semi-automated seed growing and normalized 'total white matter' T(1) histograms
      generated. Atrophy data was obtained using the Cavalieri method of modern design
      stereology. T(2) lesion volume was also determined using seed growing.T(1)
      histogram-derived measures (median, peak height, peak position and standard
      deviation) in MS patients were significantly different (p < 0.0001) from
      controls. Median T(1) correlated significantly with supratentorial (r = 0.42, p =
      0.036), lateral ventricle (r = 0.55, p = 0.004), and T(2) lesion volumes (r =
      0.84, p < 0.0001), but not with clinical parameters. Total white matter T(1)
      provides a robust, quantitative measure of global disease burden in MS, and also
      correlates significantly with cerebral atrophy. Serial studies are required to
      determine its potential role as a surrogate marker of disease progression.

PMID- 11997066
TI  - Comparison of glatiramer acetate (Copaxone) and interferon beta-1b (Betaferon) in
      multiple sclerosis patients: an open-label 2-year follow-up.
AB  - OBJECTIVE: To compare the clinical efficacy, as expressed by relapse rate and
      disability accumulation, and safety profile of glatiramer acetate (Copaxone; COP
      1) and Interferon beta-1b (Betaferon; IFN beta - 1b) administered to multiple
      sclerosis patients during a 2-year follow-up on an open-label parallel design, as
      compared to their clinical condition in the 2-year period prior to treatment.
      BACKGROUND: Copaxone and IFN beta - 1b have been recently introduced for the
      treatment of relapsing forms of MS. Both medications have been proven to have a
      relatively safe profile and are used extensively world-wide. METHODS: 58
      consecutive patients with relapsing forms of MS were enrolled from the MS out
      patient clinic, during three months. After being informed in detail of the two
      approved treatment options existing at the time in Israel, the patients chose by
      themselves to receive either: (a) Copaxone 20 mg subcutaneously (sc) daily
      (Copaxone dly, 20 patients), or (b) Copaxone 20 mg sc alternate-day (Copaxone
      alt, 18 patients) or (c) IFN beta-1b 8 MIU sc in alternate day (20 patients).
      Mean relapse rate/year and mean EDSS/year were calculated for each group of
      patients during the 2 years prior to the onset of treatment, and during the year
      prior to the onset of treatment. Statistical significance was observed in the
      relapse rate in the year prior to the onset of treatment between the IFN beta -1b
      group and the two Copaxone groups (p = 0.05). This statistical difference has no
      effect on the overall data of the 2 years prior to starting the treatment and on
      the results. No statistical significance was observed in the total number of
      relapses, and on the 2-year relapse rate, prior to the onset of treatment. Mean
      relapse rate/year and mean EDSS/year were calculated for each group during the
      first and second year of treatment. Wilcoxon analysis for clinical data and chi
      square for adverse events were applied. RESULTS: The three groups were
      statistically comparable concerning mean relapse/year in the 2 years before the
      trial started and no statistical significance was observed among the three
      groups. A statistically significant reduction in the mean relapse rate in the 2
      years after onset of treatment was observed in the three group of patients:
      Copaxone daily (dly) 1.1 +/- 0.6 (p = 0.0001); Copaxone alternate (alt) 0.9 +/-
      0.6 (p = 0.0004) and IFN beta -1b 1.2 +/- 0.7 (p = 0.0001). Disability as
      expressed by EDSS score prior to the onset of treatment and after 2 years of
      treatment showed deterioration in the three groups although more significant in
      the Copaxone groups: Copaxone dly 3.3 +/- 1.4 to 3.8 +/- 1.6 (p = 0.007);
      Copaxone alt 2.4 +/- 1.1 to 2.8 +/- 1.3 (p=0.04); IFN beta - 1b 3.1 +/- 1.3 to
      3.3 +/- 2.0 (N.S.). The most common adverse events reported were: (1) flu-like
      symptoms 7 pts (35%) in the IFN beta -1b group; 10 pts (26%) of the two Copaxone
      groups; (2) increased spasticity of lower limbs 3 pts (15%), only in the IFN beta
      -1b group; (3) site injection reaction (SIR): 16 SIR (80%) in the IFN beta -1b
      group; 12 SIR (67%) in the Copaxone alt group; 14 SIR (70%) in the Copaxone dly
      group; and (4) systemic reaction 3 pts (15%) in the IFN beta -1b group; 4 pts
      (22%) in the Copaxone alt group; 6 pts (30%) in the Copaxone dly group. Premature
      termination occurred in five patients treated with Copaxone (3 in the alternate
      group and 2 in the daily group). CONCLUSION: The present study, despite the
      limitations of an open-label study, shows that Copaxone dly, Copaxone alt and IFN
      beta -1b treatment seem to be equally effective for the control of exacerbations
      in MS. The adverse event profile, as reported by the patients, was also similar.
      However, the adverse events profile registered indicated that Copaxone is
      somewhat less detrimental, whereas disability as measured by EDSS accumulation
      showed that the interferon beta - 1b patients demonstrated a slower progression
      of the disability.

PMID- 11997067
TI  - Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile.
AB  - Devic's neuromyelitis optica (NMO) associates optic neuritis and myelitis without
      any other neurological signs. Many patients with NMO may be diagnosed as having
      multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom
      in 20% and 5% of MS cases, respectively. The aim of our study was to compare a
      new NMO cohort with recent studies and to try to determine the place of NMO in
      the spectrum of MS. We retrospectively studied 13 patients with a complete
      diagnostic workup for NMO. We compared our data with the most recent studies on
      NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999)
      1107]. We also determined whether these patients fulfilled the diagnostic
      criteria for MS. Thirteen patients (10 women and three men, with a mean age of
      37.4 years) were included in the study. We found similar results to previously
      published data, except for an association with vasculitis in 38% of our cases.
      All but three of the patients fulfilled the clinical criteria for MS and two
      patients fulfilled both clinical and MRI criteria for MS. However, if we applied
      more restrictive criteria concerning spinal cord and brain MRI and CSF, none of
      our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be
      differentiated from MS by the application of more stringent criteria.
      Furthermore, all NMO patients should be investigated for vasculitis, even those
      with no history of systemic disease.

PMID- 11997068
TI  - External ophthalmoplegia with severe progressive multiorgan involvement
      associated with the mtDNA A3243G mutation.
AB  - BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) may be related to
      primary nuclear DNA or mitochondrial (mt)DNA mutations. The A3243G mtDNA point
      mutation most frequently causes mitochondrial encephalopathy, lactic acidosis,
      and stroke-like episodes (MELAS) syndrome, but also has been associated with
      other phenotypes including CPEO, migraine, seizure, diabetes, and sensorineural
      hearing loss. CASE DESCRIPTION: We report a 38-year-old white man with seizures
      and progressive difficulties of infantile origin including CPEO, sensorineural
      hearing loss, cataracts, migraines, multiple endocrinopathy, myopathy, and
      cardiomyopathy. Moderate hearing loss in association with CPEO, diabetes
      mellitus, or migraines were noted in the proband's maternal grandmother, great
      aunt, mother, and three sisters, suggesting either an autosomal dominant or
      maternal inheritance. Detailed histological and biochemical analysis of the
      proband's biopsied muscle specimen revealed severe abnormalities compatible with
      a mitochondrial disease. MtDNA analysis excluded large-scale deletions, but
      revealed a heteroplasmic A to G transition at nt3243 in 56.4% and 27.4% of
      molecules in muscle and white blood cells, respectively. CONCLUSION: We discuss
      possible causes of this intrafamilial heterogeneity of phenotypes associated with
      the A3243G mtDNA mutation.

PMID- 11997069
TI  - Serum cytokine levels in Bell's palsy.
AB  - OBJECTIVE: To assess the significance of the serum levels of the cytokines
      (interleukine (IL-6, IL-8, IL-1b, IL-2r, and tumor necrosis factor alpha (TNF -
      alpha)) in the patients with Bell's palsy. STUDY DESIGN: A clinical and
      laboratory study in which serum cytokine levels were compared between the
      patients who had Bell's palsy and healthy controls. METHODS: Twenty-three
      patients with Bell's palsy and 30 healthy volunteers were included in the study.
      The blood samples of the patients and controls were obtained, and serum IL-1b, IL
      2r, IL-6, IL-8, and TNF- alpha levels determined with chemiluminescence enzyme
      immunometric assay on an Immulite Immunoassay. The serum of the patients was
      taken between 2 days and 1 month after the disease. The assay was not in vitro
      lymphocyte stimulation. RESULTS: The IL-6, IL-8 and TNF- alpha levels were
      significantly higher in Bell's palsy than in controls (p < 0.05). The IL-1b and
      IL-2r levels were similar in both groups (p > 0.05). The levels of cytokine IL-6,
      IL-8, TNF- alpha, IL-1b, IL-2r did not correlate with the degree of recovery (p >
      0.05). CONCLUSION: An alteration in the concentration of the cytokines is
      expected not only in many inflammatory and infectious diseases but also in Bell's
      palsy. Cytokines are not stored or preformed within cells. Therefore, high
      cytokine levels (IL-6 and IL-8, and TNF- alpha) should represent their production
      in response to underlying pathology in Bell's palsy, or these cytokines may be
      pathogenetic factors in Bell's palsy. However, serum levels of these cytokines do
      not help determine the prognosis in Bell's palsy as far as the results of this
      study are concerned.

PMID- 11997070
TI  - Clinical features and neuropathological findings of familial amyotrophic lateral
      sclerosis with a His46Arg mutation in Cu/Zn superoxide dismutase.
AB  - We examined the characteristic clinical features of one family of familial
      amyotrophic lateral sclerosis (FALS) with a His46Arg mutation in the enzyme Cu/Zn
      superoxide dismutase-1 (SOD1). The disease duration for this family was 18.1 +/-
      13.2 (mean +/- S.D.) years, with the age at onset being 39.7 +/- 10.5 years old
      (mean +/- S.D.). The initial sign was distal weakness of the unilateral lower
      limb, extending to the lower limb of the other side. A wheel chair became
      necessary at 9.8 +/- 3.2 years after the onset. Upper limb weakness started at
      15.5 +/- 8.9 years following from the onset. An autopsy was performed on a 71
      year-old woman of the family with the mutation. Her disease duration was 47
      years, and she died of pneumonia. She had no clear upper motor neuron
      involvement. Bulbar sign and respiratory muscle weakness had developed 2 years
      before her death. Neuropathological findings showed degeneration of corticospinal
      tracts, anterior/posterior spinocerebellar tracts, posterior columns, and
      Clarke's columns. There were few anterior horn cells in the lumbar spinal cord
      and no Lewy body-like hyaline inclusion bodies in these remaining anterior horn
      neurons. This is the first autopsy report of FALS with a His46Arg mutation in the
      SOD1 enzyme.

PMID- 11997071
TI  - Motor weakness and cerebellar ataxia in Sjogren syndrome--identification of
      antineuronal antibody: a case report.
AB  - We report here a combination of rare neurological manifestations of primary
      Sjogren syndrome (SS), such as motor-dominant motor weakness of peripheral
      origin, cerebellar ataxia and depression, in a Japanese female patient. An
      autoantibody in her serum and cerebrospinal fluid immunolabelled spinal motor
      neurons and cerebellar Purkinje cells. On Western blot, this antibody reacted
      with a protein of 34 kDa from the extract of spinal cord, dorsal root ganglion,
      or cerebellar cortex, which might correspond to motor weakness and cerebellar
      ataxia, respectively. The absence of its reactivity to the liver tissue indicates
      that this autoantibody targets an antigen represented exclusively in the neural
      tissues. Although it remains to be proved how autoantibodies, sometimes
      associated with SS, are involved in the development of clinical pictures, some of
      them are present in the cerebrospinal fluid and exhibit an exclusive affinity to
      neural tissues, which indicates its plausible link to neurological
      manifestations. Recognition of these antineuronal antibodies in SS will
      potentially provide a chance to treat these patients by removing or inactivating
      the antibody.

PMID- 11997072
TI  - Multiple sclerosis presenting as ataxic hemiparesis.
AB  - Multiple sclerosis (MS) can present with many clinical pictures, but only rarely
      as a lacunar syndrome. The following case presentation is of multiple sclerosis
      with initial presentation as ataxic hemiparesis (AH), indistinguishable from the
      vascular syndrome. This case serves to illustrate that even classic lacunar
      syndromes can actually be the initial manifestation of multiple sclerosis and
      that other etiologies besides ischemic stroke need to remain in the differential
      diagnosis until a definitive has been concluded.

PMID- 11997073
TI  - Hemiparkinsonism associated with a mesencephalic tumor.
AB  - A 66-year-old woman presented with a 3-year history of progressive right-sided
      hemiparkinsonism manifested by a right-hand resting tremor and right-sided
      bradykinesia. Magnetic resonance imaging (MRI) of the brain revealed a non
      enhanced polycystic mass in the left midbrain. (11)C-methylspiperone ((11)C-NMSP)
      and (18)F-fluorodopa ((18)F-DOPA) positron emission tomography (PET) revealed a
      striatal hypometabolism that was restricted to the left side. These findings are
      consistent with a dysfunction in the left nigrostriatal dopaminergic pathway that
      is presumably induced by the cystic mass in the left midbrain. This case is
      significant due to the paucity of reports regarding the occurrence of a
      relatively pure parkinsonism that is associated with a mesencephalic space
      occupying lesion.

PMID- 11997075
TI  - Stage-dependent activation of cell cycle and apoptosis mechanisms in the right
      ventricle by pressure overload.
AB  - The molecular basis of the intrinsic vulnerability of the compliant right
      ventricle to chronic pressure overload is poorly understood. Extensive apoptosis,
      possibly coupled with aberrant cell cycle reentry, in response to unrestrained
      biomechanical stress may account for this phenotypic flaw. To address this issue
      we have studied changes in expression of the cell cycle and apoptosis regulators
      in the right ventricle following induction of pulmonary hypertension in the rat
      by injection of monocrotaline. Hypertrophy, apoptosis and cell cycle events, as
      well as expression of their regulator genes were documented during a period of 31
      days. The hypertrophy index reached 127% at day 31. At the early stage both
      apoptosis and cell proliferation pathways were coincidentally activated. The
      level of cyclin A and E transcripts steadily increased, the labeling index was
      4.8% at day 31, and expression of the caspase-3 gene peaked at day 14. Until day
      21 execution of apoptosis was prevented, probably by a high level of Bcl-2. At
      this time point Bcl-2 collapsed, cyclin D1 was upregulated, the differentiation
      gatekeeper p27Kip1 was downregulated, pro-caspase-3 was activated and extensive
      apoptosis developed. These results indicate that the right ventricle is
      especially vulnerable to apoptotic pressure-dependent stimuli, and that the cell
      cycle and apoptosis pathways were co-activated in this experimental model.

PMID- 11997076
TI  - Human venous and arterial glycosaminoglycans have similar affinity for plasma low
      density lipoproteins.
AB  - We compared the glycosaminoglycan content of human venous and arterial walls. The
      most abundant glycosaminoglycan in human veins is dermatan sulfate whereas
      chondroitin 4/6-sulfate is preponderant in arteries. The concentrations of
      chondroitin 4/6-sulfate and heparan sulfate are approximately 4.8- and
      approximately 2.5-fold higher in arteries than in veins whereas dermatan sulfate
      contents are similar in the two types of blood vessels. Normal and varicose
      saphenous veins do not differ in their glycosaminoglycan contents. It is known
      that certain glycosaminoglycan species from the arterial wall, mainly high
      molecular-weight fractions of dermatan sulfate+chondroitin 4/6-sulfate have
      greater affinity for plasma LDL. These types of glycosaminoglycans can be
      identified on a LDL-affinity column. We now demonstrated that a similar
      population of glycosaminoglycan also occurs in veins, although with a lower
      concentration than in the arteries due to less chondroitin 4/6-sulfate with
      affinity for LDL. The concentrations of dermatan sulfate species, which interact
      with LDL, are similar in arteries and veins. The presence of these
      glycosaminoglycans with affinity to plasma LDL in veins raises interesting
      questions concerning the role of these molecules in the pathogenesis of
      atherosclerosis. Possibly, the presence of these glycosaminoglycans in the vessel
      wall are not sufficient to cause retention of LDL and consequently endothelial
      dysfunction, but may require additional intrinsic factors and/or the hydrodynamic
      of the blood under the arterial pressure.

PMID- 11997077
TI  - The DING protein: an autocrine growth-stimulatory protein related to the human
      synovial stimulatory protein.
AB  - A synovial stimulating protein (SSP) has previously been isolated from rheumatoid
      arthritis synovial fluid and from the culture fluid of rheumatoid arthritis
      synovial fibroblasts. We have previously isolated, from skin fibroblast cultures,
      a 40 kDa hirudin-binding protein, which had amino acid sequence homology with the
      SSP. We sought to clarify the relationship, if any, between the SSP and the
      hirudin-binding protein. We show that the hirudin-binding protein is
      immunologically cross-reactive with a protein identical with, or very similar to,
      the SSP. This hirudin-binding protein is produced by normal and rheumatoid
      arthritis fibroblasts in culture, and also by cervical carcinoma cells. Traces of
      an SSP-like protein, and of proteins intermediate in size between the SSP and the
      hirudin-binding protein, suggest that the hirudin-binding protein may be
      proteolytically derived from the SSP. An SSP-like protein of about 200 kDa is
      present in all synovial fluid samples, arthritic and normal, indicating that its
      presence is not a primary cause of rheumatoid arthritis. There is no evidence for
      the existence of smaller fragments of the SSP-like protein in synovial fluid. A
      cDNA sequence, coding for part of the 40 kDa protein, has been obtained. The
      derived amino acid sequence indicates that a domain, previously identified in the
      dishevelled gene from Drosophila melanogaster, is present in this protein.
      Peptides predicted from the cDNA sequence were used to raise antisera, which
      recognise both the 40 kDa protein and the SSP-like protein. One of the antibody
      preparations is a good inhibitor of fibroblast proliferation, which confirms the
      autocrine growth-stimulatory role originally proposed for these proteins.

PMID- 11997078
TI  - Erk 1/2 differentially regulates the expression from the 1G/2G single nucleotide
      polymorphism in the MMP-1 promoter in melanoma cells.
AB  - Matrix metalloproteinase-1 (MMP-1) breaks down interstitial collagens, a major
      component of stromal tissue and a barrier for invading tumor cells. The
      degradation of collagen by MMP-1 may, therefore, provide one mechanism for
      facilitating tumor invasion and metastasis. Because of the potential for
      excessive matrix degradation, the expression of MMP-1 is tightly regulated, often
      by the mitogen-activated protein kinase (MAPK) pathway. The MAPK signal cascade
      consists of three separate pathways, the extracellular response kinase (ERK), p38
      and Jun N-terminal kinase, which target proteins of the AP-1 and ETS families
      transcription of the gene. The MMP-1 promoter contains a single nucleotide
      polymorphism (SNP) at -1607 bp, which creates an ETS binding site by the addition
      of a guanine (5'-GGAT-3' or '2G SNP') compared to the 1G SNP (5'-GAT-3'), and
      enhances MMP-1 transcription. A2058 melanoma cells represent one tumor cell line
      that is homozygous for the 2G allele and that produces constitutively high levels
      of MMP-1. Thus, we used these cells to define the mechanism(s) responsible for
      this high level of expression. We show that inhibition of ERK 1/2 leads to the
      repression of MMP-1 transcription, and that both the 2G polymorphism and the
      adjacent AP-1 site at -1602 bp are necessary for high levels of MMP-1
      transcription and for the inhibition of MMP-1 expression by PD098059, a specific
      ERK inhibitor. Furthermore, restoration of MMP-1 levels after ERK 1/2 inhibition
      requires de novo protein synthesis of a factor necessary for MMP-1 expression.
      Thus, this study suggests that the ERK 1/2 pathway targets the 2G polymorphism,
      and that the continuous synthesis of a protein(s) is necessary for the
      constitutive expression of MMP-1.

PMID- 11997079
TI  - Molecular quality control machinery contributes to the leukocyte NADPH oxidase
      deficiency in chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease
      caused by defects in leukocyte NADPH oxidase. Various inherited defects in one of
      the membrane-bound components of NADPH oxidase, gp91-phox, cause X-linked (X91)
      CGD. Analysis of three patients with X91 CGD revealed that different mechanisms
      of molecular quality control lead to the common phenotype of absence of mature
      membrane-bound NADPH oxidase complex in leukocytes. In the first patient,
      aberrant intron splicing created a premature stop codon. However, the mutant mRNA
      was degraded prematurely, which prevented the production of truncated protein. In
      the second patient, a frameshift mutation with the potential to generate a gp91
      phox polypeptide, with an aberrant and elongated C-terminus, led to barely
      detectable levels of gp91-phox, even though the reported functional domains of
      the protein appeared unaffected. In the third patient, a point mutation created a
      single amino acid change in the predicted FAD-binding site of gp91-phox. Although
      gp91-phox was detectable with Western blotting, no cytochrome b(558) was
      expressed on the cell surface. These analyses showed that molecular quality
      control machinery plays an important role in the pathogenesis of CGD, not only in
      the X910 but also in the X91- form of this X-linked disease.

PMID- 11997080
TI  - gamma-Carboxyglutamic acid content of hepatocellular carcinoma-associated des
      gamma-carboxy prothrombin.
AB  - Serum des-gamma-carboxy prothrombin (DCP) is a useful marker for the diagnosis of
      hepatocellular carcinoma (HCC), but the exact mechanism of its synthesis and its
      structural properties in liver diseases are unknown. DCP is measured by the
      monoclonal antibody MU-3. The purpose of this study was to examine the epitope of
      MU-3 and to characterize the differences in DCP between HCC and benign liver
      diseases. The epitope of MU-3 was examined by ELISA using prothrombin Gla domain
      polypeptides and was determined to be amino acid residues 17-27 of the
      prothrombin Gla domain, which has four gamma-carboxyglutamic acid residues (Gla)
      at positions 19, 20, 25 and 26. Peptides having a glutamic acid residue (Glu) at
      these positions reacted strongly to MU-3 but lost reactivity when Glu 19 or 20
      was changed to Gla. In the order of gamma-carboxylation, MU-3 reacted strongly to
      DCP containing 0-1 Gla, weakly to 2-4 Gla and not at all to DCP containing more
      than five Gla. After adsorbing normal prothrombin with barium carbonate, DCP
      reaction to MU-3 was measured by determining the amount of DCP that was adsorbed
      by MU-3-coated beads. The proportion of DCP reacting to MU-3 in HCC was 41.0
      76.8%, whereas in patients with benign liver diseases, only 0-42.1% reacted to MU
      3. These results indicate that DCP variants preferentially synthesized in HCC
      have less than four Gla, which are restricted to positions 16, 25, 26 and 29,
      whereas DCP variants in benign liver diseases have more than five Gla.

PMID- 11997081
TI  - Saturation of adrenomedullin receptors plays an important role in reducing
      pulmonary clearance of adrenomedullin during the late stage of sepsis.
AB  - Adrenomedullin (AM) is a potent vasodilator that plays a major role in the
      cardiovascular response during the progression of sepsis. Although pulmonary
      clearance of AM (i.e., the primary site of AM clearance) is reduced during the
      late, hypodynamic stage of sepsis, the role of AM receptors under such conditions
      remains unclear. This study was carried out to test the hypothesis that
      saturation of AM receptors is responsible for the decreased clearance of AM in
      the lungs during sepsis. Polymicrobial sepsis was induced in male adult rats by
      cecal ligation and puncture (CLP). At 20 h after CLP (i.e., the late phase), 125I
      labeled rat AM was administered through the jugular vein, both with (+) and
      without (-) pre-injection of the human AM fragment AM(22-52) (an AM receptor
      antagonist). Pulmonary tissue samples were harvested after 30 min and the
      radioactivity was determined. In addition, lung levels of AM were determined at 5
      and 20 h after CLP by radioimmunoassay. Alterations in gene expression of the
      recently identified AM receptor subunits calcitonin receptor-like receptor (CRLR)
      and receptor activity modifying protein-2 and -3 (RAMP-2 and -3) were assessed in
      the lungs by reverse transcription-polymerase chain reaction (RT-PCR) at 5 and 20
      h after CLP. The results indicate that there was a significant decrease in
      pulmonary [125I]AM clearance at 20 h in -AM(22-52) CLP animals. Lung clearance in
      +AM(22-52) sham animals was significantly lower than in -AM(22-52) sham animals
      and was not statistically different from the -AM(22-52) CLP group. There was no
      statistical difference between +AM(22-52) and -AM(22-52) CLP groups. However,
      there was a significant increase in lung AM levels at 20 but not 5 h after CLP.
      In addition, RAMP-3 expression was significantly upregulated at 5 but not 20 h
      after CLP. There were no alterations in the expression of CRLR or RAMP-2 at
      either time point. These results suggest that pulmonary AM receptors become
      saturated as more AM enters the bloodstream, thereby reducing the ability of the
      lungs to clear this peptide during late sepsis. Early upregulation of RAMP-3 may
      be a compensatory mechanism to help clear the upregulated AM from the
      bloodstream. The lack of upregulation of RAMP-3 during late sepsis could also
      contribute to the decreased clearance observed during this phase.

PMID- 11997082
TI  - Alterations in promoter usage and expression levels of insulin-like growth factor
      II and H19 genes in cervical carcinoma exhibiting biallelic expression of IGF-II.
AB  - Biallelic expression of insulin-like growth factor-II (IGF2) has been reported to
      be associated with progression of several tumors. Here, we report that the
      promoter usage and expression levels of IGF2 and H19 were altered in cervical
      carcinoma showing loss of imprinting. The imprinting status was examined in 32
      cervical carcinomas and their matched normal tissues. Loss of imprinting (LOI) of
      IGF2 was observed in seven of 18 (39%) informative cases. LOI of H19 gene was
      detected in five of 14 informative cases. The usage of promoter P1 was observed
      in LOI tumors of IGF2, but not in the tumors showing maintenance of IGF2
      imprinting (MOI) and in the normal cervical tissues. Unlike MOI tumors, some LOI
      tumors revealed the lack of IGF2 transcription from promoter P3. LOI tumors of
      IGF2 showed an increased expression level of IGF2 but a down-regulation of H19
      relative to the normal tissues whereas MOI tumors did not reveal significant
      alterations. These results suggest that promoter P1 could be involved in the
      biallelic expression of IGF2 and that the altered expression levels of IGF2 and
      H19 gene might be associated with the progression of cervical carcinoma showing
      biallelic expression of IGF2.

PMID- 11997083
TI  - Molecular and functional characterization of a new X-linked chronic granulomatous
      disease variant (X91+) case with a double missense mutation in the cytosolic
      gp91phox C-terminal tail.
AB  - We report here two atypical cases of X-linked CGD patients (first cousins) in
      which cytochrome b(558) is present at a normal level but is not functional
      (X91+). The mutations were localized by single-strand conformational polymorphism
      of reverse transcriptase-polymerase chain reaction amplified fragments and then
      identified by sequence analysis. They consisted in two base substitutions (C919
      to A and C923 to G), changing His303 to Asn and Pro304 to Arg in the cytosolic
      gp91phox C-terminal tail. Mismatched polymerase chain reaction and genomic DNA
      sequencing showed that mothers had both wild-type and mutated alleles, confirming
      that this case was transmitted in an X-linked fashion. A normal amount of FAD was
      found in neutrophil membranes, both in the X91+ patients and their parents.
      Epstein-Barr virus-transformed B lymphocytes from the X91+ patients acidified
      normally upon stimulation with arachidonic acid, indicating that the mutated
      gp91phox still functioned as a proton channel. A cell-free translocation assay
      demonstrated that the association of the cytosolic factors p47phox and p67phox
      with the membrane fraction was strongly disrupted. We concluded that residues 303
      and 304 are crucial for the stable assembly of the NADPH oxidase complex and for
      electron transfer, but not for its proton channel activity.

PMID- 11997084
TI  - Molecular basis of renal handling of calcium in response to thyroid hormone
      status of rat.
AB  - We investigated the effect of thyroid hormone status on renal handing of Ca2+.
      Further, like kinetics of Ca2+ transport across brush-border membrane (BBM) and
      basolateral membrane (BLM) of renal epithelial cells was carried out. FE(Ca) was
      decreased in hyperthyroid (Hyper-T) rats and increased in hypothyroid (Hypo-T)
      rats as compared to euthyroid (Eu-T) rats. Ca2+ uptake into renal brush-border
      membrane vesicles (BBMV) was increased in Hyper-T rats and decreased in Hypo-T
      rats as compared to Eu-T rats. K(m) was lower in Hyper-T rats and higher in Hypo
      T rats as compared to Eu-T rats whereas, V(max) remained unaltered. The
      transition temperature for calcium uptake varied inversely with the thyroid
      hormone status. Renal BBM of Hyper-T rats showed decreased anisotropy and
      polarisation of DPH as compared to EU-T rats whereas these values were increased
      in Hypo-T rats. Thus, the altered BBM fluidity appears to modulate Ca2+ transport
      across BBM. Na+/Ca2+ exchange activity of renal cells was increased in Hyper-T
      and decreased in Hypo-T rats as compared to Eu-T rats. V(max) for Na+/Ca2+
      exchange was increased in Hyper-T rats and deceased in Hypo-T rats as compared to
      Eu-T rats, whereas, [Na+](0.5) was similar in all three groups. The c-AMP levels
      of renal cortex of Hyper-T rats was increased and that of Hypo-T rats decreased
      as compared to Eu-T rats. Thus, thyroid hormones increased Ca2+ reabsorption in
      the kidney of rat. Thyroid hormone-mediated modulation of BBM fluidity appears to
      stimulate Ca2+ uptake into renal BBMV. Thyroid hormones possibly activated the
      Na+/Ca2+ exchanger through cAMP-dependent pathway.

PMID- 11997085
TI  - Experimental hyperphenylalaninemia provokes oxidative stress in rat brain.
AB  - Tissue accumulation of L-phenylalanine (Phe) is the biochemical hallmark of human
      phenylketonuria (PKU), an inherited metabolic disorder clinically characterized
      by mental retardation and other neurological features. The mechanisms of brain
      damage observed in this disorder are poorly understood. In the present study we
      investigated some oxidative stress parameters in the brain of rats with
      experimental hyperphenylalaninemia. Chemiluminescence, total radical-trapping
      antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GSH-Px) activities were measured in the brain of the
      animals. We observed that chemiluminescence is increased and TRAP is reduced in
      the brain of hyperphenylalaninemic rats. Similar data were obtained in the in
      vitro experiments using Phe at various concentrations. CAT activity was
      significantly inhibited by Phe in vitro and in vivo, whereas GSH-Px activity was
      reduced in vivo but not in vitro and SOD activity was not altered by any
      treatment. The results indicate that oxidative stress may be involved in the
      neuropathology of PKU. However, further studies are necessary to confirm and
      extend our findings to the human condition and also to determine whether an
      antioxidant therapy may be of benefit to these patients.

PMID- 11997086
TI  - A human short-chain dehydrogenase/reductase gene: structure, chromosomal
      localization, tissue expression and subcellular localization of its product.
AB  - We have previously described the cloning of Hep27, a short-chain
      dehydrogenase/reductase, which is synthesized in human hepatoblastoma HepG2 cells
      following growth arrest induced by butyrate treatment. The present report
      describes the cloning, the structure and the physical and cytogenetic mapping of
      the gene coding for Hep27. We also show that Hep27 is synthesized in a limited
      number of human normal tissues and that it is localized in the nuclei and
      cytoplasm of HepG2 cells.

PMID- 11997087
TI  - The interaction of DNA-targeted 9-aminoacridine-4-carboxamide platinum complexes
      with DNA in intact human cells.
AB  - As part of an ongoing drug development programme, this paper describes the
      sequence specificity and time course of DNA adduct formation for a series of
      novel DNA-targeted analogues of cis-diaminedichloroplatinum(II) (cisplatin) (9
      aminoacridine-4-carboxamide Pt complexes) in intact HeLa cells. The sequence
      specificity of DNA damage caused by cisplatin and analogues in human (HeLa) cells
      was studied using Taq DNA polymerase and a linear amplification/polymerase stop
      assay. Primer extension is inhibited by a Pt-DNA adduct, and hence the sites of
      these lesions can be analysed on DNA sequencing gels. The repetitive alphoid DNA
      sequence was used as the target DNA in human cells. The 9-aminoacridine-4
      carboxamide Pt complexes exhibited a markedly different sequence specificity
      relative to cisplatin and other analogues. The sequence specificity of the 9
      aminoacridine-4-carboxamide Pt complexes is shifted away from a preference for
      runs of guanines. The 9-aminoacridine-4-carboxamide Pt complexes have an enhanced
      preference for GA dinucleotides. This is the first occasion that an altered DNA
      sequence specificity has been demonstrated for a cisplatin analogue in human
      cells. A time course of DNA damage revealed that the DNA-targeted Pt complexes,
      consisting of four 9-aminoacridine-4-carboxamide Pt complexes and one acridine-4
      carboxamide Pt complex, damaged DNA more rapidly compared to cisplatin and non
      targeted analogues. A comparison of the time taken to reach half the maximum
      relative intensity indicated that the DNA-targeted Pt complexes reacted
      approximately 4-fold faster than cisplatin and the non-targeted analogues.

PMID- 11997088
TI  - Identification of a novel nuclear factor-binding site in the Pisum sativum sad
      gene promoters.
AB  - DNA fragments containing the 5' promoter regions of the Pisum sativum sadA and
      sadC genes were amplified from genomic DNA, cloned and sequenced. These sequences
      contain a number of conserved cis-acting elements, which are potentially involved
      in stress-induced transcription of the sad genes. To determine whether any of the
      identified elements are active in binding nuclear factors in vitro, 11 60-bp
      overlapping (by 30 bp) DNA probe fragments covering the proximal sadC promoter
      sequence (360 bp) were used in electrophoretic mobility shift assays with
      competition. Binding activities were compared in nuclear extracts from control,
      UV-B-stressed and wounded pea leaves. The pattern of DNA binding was almost
      identical with all three extracts, with one 30-bp region being the predominant
      site for factor binding. Using overlapping sub-fragments of this region, the
      majority of the specific binding could be attributed to the novel 11-bp GC-rich
      sequence GTGGCGCCCAC. An almost identical sequence is conserved in the sadA
      promoter. This motif has features in common with a number of recognised cis
      elements, which suggests a possible binding site for factors which play a role in
      regulating sad gene transcription.

PMID- 11997089
TI  - Structural gene organization and evolutionary aspects of the V-ATPase accessory
      subunit Ac45.
AB  - The vacuolar H+-ATPase (V-ATPase) is a multisubunit enzyme that couples ATP
      hydrolysis to proton pumping across membranes. The intracellular targeting and
      activity of the V-ATPase may be regulated via proteins that interact with the
      pump such as the accessory subunit Ac45. Here we report the isolation and
      characterization of the gene encoding Ac45. This single-copy gene is located in a
      gene-dense region of chromosome Xq and consists of 10 exons spanning
      approximately 8 kb in the mouse and human genomes. The gene structure is poorly
      conserved in that its invertebrate orthologs of Caenorhabditis elegans and
      Drosophila melanogaster encompass only six and four exons extending over 4.1 and
      2.1 kb, respectively. Furthermore, the overall degree of amino acid sequence
      identity between the mammalian and invertebrate Ac45 proteins is very low (<18%),
      except for a surprisingly highly conserved putative targeting motif in the
      carboxy-terminal region. Primer extension analysis revealed that the mouse Ac45
      gene contains two major transcription initiation sites. The start sites are not
      preceded by a clear CAAT-box and are located in a CpG island. The most downstream
      start site contains a TATA-box and transcriptional regulatory elements such as
      PEA-3, F2F, Maz and Sp1. The limited number of regulatory DNA elements common in
      the genes encoding Ac45 and V-ATPase subunits suggests a differential regulation
      of these genes. Together with the finding that Ac45 appears to occur only in
      multicellular organisms, these results indicate that this accessory subunit
      directs the V-ATPase to specialized and complex vacuolar systems.

PMID- 11997090
TI  - RPL29 codes for a non-essential protein of the 60S ribosomal subunit in
      Saccharomyces cerevisiae and exhibits synthetic lethality with mutations in genes
      for proteins required for subunit coupling.
AB  - RPL29 (YFR032c-a) is a non-essential gene that codes for a 60S ribosomal subunit
      protein in Saccharomyces cerevisiae. Deletion of RPL29 leads to a moderate
      accumulation of half-mer polysomes with little or no change in the amounts of
      free 60S subunits. In vitro translation and the growth rate are also delayed in
      the Deltarpl29 strain. Such a phenotype is characteristic of mutants defective in
      60S to 40S subunit joining. The Deltarpl29 strain exhibits synthetic lethality
      with mutations in RPL10, the gene encoding an essential 60S ribosomal subunit
      protein that is required for 60S to 40S subunit joining. The Deltarpl29 strain
      also exhibits synthetic lethality with RSA1, a gene encoding a nucleoplasmic
      protein required for the loading of Rpl10p onto the 60S subunit. Over-expression
      of RPL10 suppresses the half-mer phenotype of the Deltarpl29 strain, but does not
      correct the growth defect of the deletion strain. We conclude that absence of
      Rpl29p impairs proper assembly of proteins onto the 60S subunit and that this
      retards subunit joining and additionally retards protein synthesis subsequent to
      subunit joining.

PMID- 11997091
TI  - The human alphaE-catenin gene CTNNA1: mutational analysis and rare occurrence of
      a truncated splice variant.
AB  - Abnormal expression of the alphaE-catenin protein, a component of the E
      cadherin/catenin cell adhesion complex, is frequently observed in human cancer
      cells. An inverse correlation between alphaE-catenin expression and tumor
      malignancy can be of prognostic value. Mutations of the alphaE-catenin gene,
      CTNNA1, were described in several human cancer cell lines and were found to
      result in aberrant cell adhesion. We have developed a polymerase chain
      reaction/single-strand conformation polymorphism-based method for mutation
      analysis of this gene in human tumor DNA. This approach enabled us to identify
      several polymorphisms in a set of desmoid tumors, demonstrating that this method
      is suitable for alphaE-catenin mutational analysis. On the basis of our genomic
      characterization data, we found that the previously reported alternative splicing
      of the alphaE-catenin gene actually generates a frame-shift, resulting in a
      truncated alphaE-catenin protein. This finding is unlike the other alpha-catenin
      family members alphaN-catenin and vinculin, which show in-frame alternative
      inserts. Furthermore, real-time quantitative reverse transcriptase-PCR analysis
      did not reveal relevant expression levels of this alternatively spliced alphaE
      catenin variant neither in any human tissue or cell line tested, nor at any mouse
      developmental stage tested. Thus, contrary to previous notions, alternative
      splicing with in-frame insertion nearby the C-terminal end of the protein is not
      a general feature for all members of the alpha-catenin/vinculin family.

PMID- 11997092
TI  - Characterization of human SMARCE1r high-mobility-group protein.
AB  - The high-mobility-group (HMG) proteins are chromatin-associated proteins that are
      common to all higher organisms. They bind DNA in a sequence-specific or non
      sequence-specific way to induce DNA bending, and regulate chromatin function and
      gene expression. Here we report the characterization of an HMG box-containing
      gene, designated human Smarce1r gene. It contained an open reading frame (ORF)
      encoding 317 amino acids and had 86% and 94% identity with the murine Smarce1r
      ORF at the nucleic acid and amino acid level, respectively. A putative nuclear
      localization signal, one HMG domain, and a coiled-coil domain were localized. A
      single transcript of 1.6 kb was ubiquitously expressed in various human tissues
      except for the fetal brain in which the transcript was barely detected. Western
      blot analysis revealed that human SMARCE1r was expressed in specific tissues such
      as colon and placenta. Subcellular fractionation, DNA-affinity column
      chromatography, and electrophoretic mobility shift assays showed that human
      SMARCE1r was associated with the nuclear matrix and that it possessed DNA binding
      activity, as expected.

PMID- 11997093
TI  - Expression of the chicken homologue of the mouse double minute 2 gene.
AB  - While the p53 tumor suppressor plays a crucial role in regulating cell cycle
      checkpoints and apoptosis by acting as either a transcriptional activator or
      repressor in a variety of mammalian cells, its evolutionarily conserved functions
      remain to be elucidated in non-mammalian species. In the present study, we
      determined the functional role of p53 in avian cells by analyzing the expression
      pattern of the chicken homologue (CDM2) of mouse double minute 2, one of the
      transcriptional target genes of p53. CDM2 displayed considerable conservation in
      the p53 binding region as well as the nuclear localization and nuclear export
      signals and was found to be abundantly expressed in the reproductive organs
      (testis and ovarian follicles) and in the immune organs (bone marrow, bursa and
      thymus). CDM2 expression exhibited an early serum-response pattern consistent
      with its mammalian counterparts and was dramatically downregulated in most of the
      p53-downregulated immortal chicken embryo fibroblast (CEF) cells analyzed.
      Expression of CDM2 was shown to be transcriptionally upregulated in the primary
      CEF cells where p53 was activated by either mitomycin C treatment or by the
      exogenous transfection of the chicken p53 cDNA. Together, the current studies
      demonstrate that the expression of MDM2 homologues may be biologically conserved
      in mammalian and avian cells.

PMID- 11997094
TI  - Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine
      transporter, in relation to urea cycle in mice.
AB  - The present report describes the expression profiles of different tissues and
      developmental changes of mouse aspartate/glutamate carrier (AGC) genes, Slc25a13
      and Slc25a12, and an ornithine transporter gene, Ornt1, in relation to urea cycle
      enzyme genes, carbamoylphosphate synthetase I (CPS) and argininosuccinate
      synthetase (ASS). Slc25a13 encodes citrin, recently found to be deficient in
      adult-onset type II citrullinemia and to function as AGC together with its
      isoform and product of Slc25a12, aralar1. Citrin was broadly distributed, but
      mainly in the liver, kidney and heart. Aralar1 was expressed in diaphragm,
      skeletal muscle, heart, brain and kidney, but not in the liver. These
      distribution profiles are different from the restricted of Ornt1, ASS and CPS.
      Citrin, ASS, CPS and Ornt1 showed similar patterns of developmental changes in
      the liver and small intestine, where they play a role in urea and arginine
      synthesis. Dietary, hormonal and physical manipulations caused varied changes of
      CPS, ASS and Ornt1 in the liver, but the change of citrin was not so marked as
      that of the others. Analysis using RT-PCR and restriction enzyme digestion
      revealed that the ornithine transporter most expressed is Ornt1, although Ornt2
      is detectable at a minute level. All these results suggest that citrin as AGC
      plays a role in urea synthesis as well as many fundamental metabolic pathways in
      the liver, and shares metabolic functions with aralar1 in other tissues, and that
      Ornt1 is an important component in urea synthesis in the liver and in arginine
      synthesis in the small intestine during the neonatal period.

PMID- 11997095
TI  - A highly expressed family 1 beta-glucosidase with transglycosylation capacity
      from the anaerobic fungus Piromyces sp. E2.
AB  - Anaerobic fungi have very high cellulolytic activities and thus degrade cellulose
      very efficiently. In cellulose hydrolysis, beta-glucosidases play an important
      role in prevention of product inhibition because they convert oligosaccharides to
      glucose. A beta-glucosidase gene (cel1A) was isolated from a cDNA library of the
      anaerobic fungus Piromyces sp. E2. Sequence analysis revealed that the gene
      encodes a modular protein with a calculated mass of 75800 Da and a pI of 5.05. A
      secretion signal was followed by a negatively charged domain with unknown
      function. This domain was coupled with a short linker to a catalytic domain that
      showed high homology with glycosyl hydrolases belonging to family 1. Southern
      blot analysis revealed the multiplicity of the gene in the genome. Northern
      analysis showed that growth on fructose resulted in a high expression of cel1A.
      The cel1A gene was successfully expressed in Pichia pastoris. The purified
      heterologously expressed protein was shown to be encoded by the cel1A gene by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) analysis of a tryptic digest. Purified heterologous Cel1A was
      active towards several artificial and natural substrates with beta-1-4 linked
      glucose molecules with a remarkably high activity on cellodextrins. The enzyme
      was strongly inhibited by D-glucono-1,5-delta-lactone (K(i)=22 microM), but
      inhibition by glucose was much less (K(i)=9.5 mM). pH and temperature optimum
      were 6 and 39 degrees C, respectively. The enzyme was fairly stable, retaining
      more than 75% of its activity when incubated at 37 degrees C for 5 weeks.
      Transglycosylation activity could be demonstrated by MALDI-TOF MS analysis of
      products formed during degradation of cellopentaose.

PMID- 11997096
TI  - Element analysis of the Polysphondylium pallidum gp64 promoter.
AB  - gp64 mRNA in Polysphondylium pallidum is expressed extensively during vegetative
      growth, and begins to rapidly decrease at the onset of development. To examine
      this unique regulation, 5' deletion analysis of the gp64 promoter was undertaken,
      and two growth-phase activated elements have been found: a food-dependent,
      upstream regulatory region (FUR, -222 to -170) and a vegetatively activated,
      downstream region (VAD, -110 to -63). Here we concentrate our analysis on an A1
      and A2 sequences in the FUR region: A1 consists of a GATTTTTTTA sequence called a
      corresponding sequence and A2 consists of the direct repeat TTTGTTGTG. The cells
      carrying a combined construct of A1 and A2 acted synergistically in a reporter
      activity. A point mutation analysis in A1 indicates that a G residue is required
      for the activation of A1. From analyses of promoter regulation in a liquid or a
      solid medium, the promoter activity of the cells fed on bacteria in A-medium
      (axenic medium for Polysphondylium) or grown in A-medium alone was only one
      fourth of that of the cells fed on bacteria. By the gel retardation, we detected
      a protein bound to the A1 sequence.

PMID- 11997097
TI  - Genomic organization of the gene that encodes the precursor to EGF-related
      peptides, exogastrula-inducing peptides, of the sea urchin Anthocidaris
      crassispina.
AB  - Exogastrula-inducing peptides (EGIPs) were identified in embryos of the sea
      urchin Anthocidaris crassispina as polypeptides with structural similarity to
      epidermal growth factor (EGF) that severely affect gastrulation of sea urchin
      embryos to induce exogastrulation. Here we have obtained genomic clones for the
      EGIP precursor gene (EGIP) and determined its genomic organization. The EGIP gene
      spans the length of 9 kb in the genome and is composed of seven exons and six
      introns. Each of the four EGF motifs in the precursor protein is encoded by a
      single exon, and all the exon boundaries are in phase 1, suggesting that EGIP
      have been generated during evolution by duplication of an exon encoding a single
      ancient EGIP sequence. The 5'-flanking sequence of EGIP from -4372 to +194
      revealed the presence of multiple repeat sequences including direct and inverted
      repeats as well as two clusters of GGGG/CCCC elements. The function of the
      upstream flanking region of EGIP was examined by introducing the gene constructs
      into embryos in which different regions from the flanking DNA were placed
      upstream to the GFP reporter gene. Systematic deletion of the upstream DNA
      revealed the presence of potent enhancer activity between -372 and -210.

PMID- 11997098
TI  - The EF-hand calcium-binding protein calmyrin inhibits the transcriptional and DNA
      binding activity of Pax3.
AB  - Pax3 is a member of the paired class homeodomain family of transcription factors
      and has been demonstrated to be an early marker in myogenic differentiation. To
      gain a better understanding of how protein-protein interactions regulate Pax3
      transcriptional activity, we performed a yeast two-hybrid analysis to identify
      proteins that interact with Pax3. Screening of two cDNA libraries isolated nine
      independent clones that contained the complete encoding sequence of the EF-hand
      calcium-binding protein calmyrin. In this report, we demonstrate that calmyrin
      specifically interacts with Pax3 in vitro. In addition, we demonstrate that the
      interaction between Pax3 and calmyrin is mediated by the region of the Pax3
      paired domain that is involved in making DNA contacts and the Pax3 octapeptide
      domain and its surrounding amino acid sequences. We also demonstrate that
      endogenous Pax3 and calmyrin are co-expressed in undifferentiated primary
      myoblasts and that calmyrin expression levels increase in the nucleus upon
      myogenic differentiation. Finally, we demonstrate that co-expression of calmyrin
      with Pax3 inhibits the transcriptional activity of Pax3 by inhibiting Pax3 from
      binding to its recognition DNA sequences. These results therefore suggest
      potential ways in which calcium, through its regulation of the EF-hand calcium
      binding protein calmyrin, can alter the DNA-binding activity and subsequent
      transcriptional activity of Pax3.

PMID- 11997099
TI  - Developmental expression of trehalase: role of transcriptional activation.
AB  - The third postnatal week of mouse development is characterized by dramatic
      changes of gene expression in the small intestine. Although these changes are
      often assumed to reflect regulation at the level of transcription, to date there
      have been no direct investigations of this. In the current study we have used
      trehalase as a marker of intestinal maturation. Highly sensitive reverse
      transcriptase-polymerase chain reaction methods were developed for semi
      quantitative analysis of both initial and mature transcripts, i.e., hnRNA and
      mRNA. Jejunums collected during normal development (specifically from postnatal
      days 8-21) showed parallel increases in the levels of trehalase hnRNA and mRNA.
      Likewise, when precocious gut maturation was elicited by dexamethasone
      administration on days 8-10, both initial and mature trehalase transcripts were
      significantly increased, although with a relatively slow time course. We conclude
      that both normal and glucocorticoid-induced maturation of trehalase expression
      reflect transcriptional activation. However, the slow time course of the
      glucocorticoid effect suggests that trehalase may not be a primary response gene.

PMID- 11997100
TI  - Cell-type dependency of two Foxa/HNF3 sites in the regulation of vitronectin
      promoter activity.
AB  - The mouse vitronectin promoter has two consensus sequences of the Foxa/hepatocyte
      nuclear factor (HNF) 3-binding site (from -34 to -25, site A, and +15 to +26 base
      pairs (bp), site B). Site-directed mutagenesis of site B inhibited binding of
      nuclear proteins from mouse neuroblastoma Neuro2a and reduced the promoter
      activity to 4.6% in a 101-bp fragment (from -48 to +53 bp) in Neuro2a cells. The
      nuclear proteins of site B were identified as the Foxa1/HNF3alpha and
      Foxa2/HNF3beta proteins by supershift assay. Next, we examined site A. Mutation
      of site A in Neuro2a cells did not affect the promoter activity, and binding of
      nuclear proteins was not detected. Overexpression of Foxa1 or Foxa2 protein
      activated the mutated site B promoter, but failed to activate the sites A and B
      double-mutated promoter in Neuro2a cells, indicating that site A is a potential
      transcription regulatory site. Recombinant Foxa1 and Foxa2 proteins and nuclear
      extract from mouse liver bound not only to site B, but also to site A. In human
      hepatoma HepG2 cells, mutation of sites A and B decreased the promoter activity
      to 82% and 38%, respectively, in the wild promoter, and double mutation of sites
      A and B decreased the wild promoter activity to 5%, indicating that sites A and B
      contribute to the promoter activity in HepG2 cells. These results demonstrate
      that the two Foxa-binding sites regulate the vitronectin promoter activity in
      cell type-dependent manner.

PMID- 11997101
TI  - Genomic organization and promoter regulation of human cytochrome c oxidase
      subunit VII heart/muscle isoform (COX7AH).
AB  - We have isolated and characterized the human gene (COX7AH) for the contractile
      muscle isoform of cytochrome c oxidase (COX) subunit VIIa. This subunit is one of
      the 10 nuclear encoded subunits of the 13-subunit holoenzyme that carries out the
      terminal step in the electron transport chain. Using transient transfection
      assays, we have located a 5'-flanking region sufficient to direct high level,
      skeletal myotube-specific reporter gene expression. This 792 bp basal promoter,
      which contains the single transcription start but no canonical TATA or CCAAT
      boxes, contains one MEF2 site, three E boxes, and an Sp1 site that show binding
      to their cognate factors, and are all required for full expression. Mutation and
      transactivation analysis suggest that there is functional interaction between
      these binding sites.

PMID- 11997102
TI  - Cloning and characterization of the 5'-flanking region of the rat P4Halpha gene
      encoding the prolyl 4-hydroxylase alpha(I) subunit.
AB  - Prolyl 4-hydroxylase (P4H), an alpha(2)beta(2) tetramer, plays a crucial role in
      collagen synthesis. It catalyzes the hydroxylation of proline residues in X-Pro
      Gly sequences to form 4-hydroxyproline. We isolated a genomic clone of the rat
      P4Halpha(I) gene. Approx. 0.6 kb of the fragment, which contained the 5'-flanking
      region, exon 1, and intron 1, was sequenced. Computer analysis revealed several
      motifs that may act as binding sites for basal transcription factors. To
      elucidate the regulation of the rat P4Halpha(I) gene expression, we assessed the
      0.6 kb 5'-flanking region of the P4Halpha(I) gene for basal promoter activity. A
      series of deletion mutants of the 5'-flanking region linked to the luciferase
      gene was constructed. The basal expression level of these constructs was
      determined in fetal rat lung fibroblasts and Hepa-1 hepatoma cells. By measuring
      the luciferase activity, we found a positive-regulatory region at positions -246
      to -165 bp.

PMID- 11997103
TI  - Characterization and identification of promoter elements in the mouse COX17 gene.
AB  - Cox17p, essential for the assembly of functional cytochrome c oxidase (CCO) in
      Saccharomyces cerevisiae, has been believed to deliver copper ions to the
      mitochondrion for insertion into the enzyme. We have recently isolated an
      approximately 20 kb genomic fragment of the mouse COX17. Reporter assay
      experiments have shown that most of the promoter activity was restricted to a
      0.85 kb fragment flanking the first exon. Further intensive deletion and detailed
      mutation analysis suggested that the minimal essential region for transactivation
      was located at bases -155 to -70. This 5'-flanking region did not possess a TATA
      box, but contained putative Sp1, NRF-1 and NRF-2 binding sites. COX17 basal
      promoter activity was abrogated by site-directed mutagenesis of Sp1, NRF-1 and
      NRF-2 binding sites. Electrophoretic mobility shift assays with AtT-20 and NIH3T3
      cell nuclear extract revealed that this region binds both a Sp1-like protein and
      NRF-1 transcription factors. These results indicated that Sp1, NRF-1 and NRF-2
      are involved in basal transcription of the COX17 gene, similar to the
      transcription mechanism of other CCO-related genes.

PMID- 11997104
TI  - Characterization of the 5'-flanking region of the human PTK6 gene.
AB  - PTK6 (also known as Brk) is a non-receptor protein tyrosine kinase, whose mRNA
      was expressed in the limited normal tissues such as colon and small intestine,
      and in breast carcinomas and breast cancer cell lines. The 813 bp region upstream
      from the translation initiation codon, which constitutes a functional promoter of
      the human PTK6 gene, was progressively deleted and fused to the luciferase
      reporter gene and transient expression of the resultant constructs was measured
      upon transfection into a breast carcinoma cell line, T-47D. Comparative analysis
      of luciferase activity revealed two major regions, -93 to -76 and -702 to -655,
      important for transcriptional regulation. The proximal -93 to -76 region was
      found to be essential for the function of the minimal promoter. By primer
      extension and PCR, it was shown that a PTK6 transcript started at the most 5'
      upstream is located around base -104. Therefore, the proximal -93 to -76 region
      is thought to function as a downstream cis-acting element. Luciferase analysis
      showed that the distal -702 to -655 region contained at least two cis-acting
      elements. Gel mobility shift assays with T-47D nuclear extract including
      competition analyses with consensus and mutant oligonucleotides and supershift
      analyses with NF-kappaB and Sp1 antibodies showed that NF-kappaB binds to the
      sequence from -706 to -688 and Sp1 binds to the sequence from -688 to -669. This
      study thus provides the first molecular insights into the transcriptional
      regulation of the human PTK6 gene.

PMID- 11997105
TI  - Isolation of a cotton RGP gene: a homolog of reversibly glycosylated polypeptide
      highly expressed during fiber development.
AB  - A full-length cDNA encoding putative reversibly glycosylated polypeptide (RGP)
      was cloned from cotton fiber cells using differential display combined with rapid
      amplification of the cDNA ends. The gene, designated GhRGP1, contains an open
      reading frame of 1080 bp encoding a protein of 359 amino acids which has 78-86%
      identity with other plant RGPs. Northern blot analysis showed that the gene is
      preferentially expressed in fiber cells and its transcripts are abundant both at
      the primary cell wall elongation stage and at the later stage of secondary cell
      thickening, suggesting that GhRGP1 may be involved in non-cellulosic
      polysaccharide biosynthesis of the plant cell wall.

PMID- 11997106
TI  - Cloning, chromosomal organization and expression analysis of Neurl, the mouse
      homolog of Drosophila melanogaster neuralized gene.
AB  - The Drosophila neuralized (neur) gene belongs to the neurogenic group of genes
      involved in regulating cell-cell interactions required for neural precursor
      development. neur mutant phenotypes include strong overcommitment to neural fates
      at the expense of epidermal fates. The human neuralized homolog (NEURL) has been
      recently determined and found to map to chromosome 10q25.1 within the region
      frequently deleted in malignant astrocytomas. Because of its potential importance
      in developmental processes, we analyzed the structure of the mouse homolog,
      Neurl, and its expression pattern in embryonic tissues. Neurl activity is
      detected from early developmental stages in several tissues and organs including
      neural tissues, limbs, the skeletal system, sense organs and internal organs
      undergoing epithelial-mesenchymal interactions. Neurl encodes a polypeptide
      associated with the plasma membrane but also detected in the cytoplasm. Similarly
      to the Drosophila gene, mammalian neuralized may code for an important regulatory
      factor.

PMID- 11997107
TI  - Identification and characterization of an isoform of murine Mpl.
AB  - A new isoform of the full-length murine thrombopoietin (Tpo) receptor was
      isolated from a murine spleen cDNA library. This isoform, c-mpl-II, differs from
      full-length c-mpl (c-mpl-I) by virtue of deletion of 180 nucleotides that encode
      60 amino acids located in the extracellular domain of Mpl. Normal murine
      megakaryocytes were found to express both c-mpl-I and c-mpl-II transcripts. BaF3
      cells transfected with c-mpl-I expressed a 95 kDa protein that was displayed on
      the cell surface and bound 125I-Tpo. BaF3 cells transfected with c-mpl-II
      expressed a 70 kDa protein. However, these cells were not able to bind 125I-Tpo
      and surface display of Mpl-II could not be detected. In summary, c-mpl-II is an
      isoform of murine Mpl expressed by megakaryocytes that lacks a 60 amino acid
      region required for surface expression of the protein.

PMID- 11997108
TI  - Z39Ig is co-expressed with activated macrophage genes.
AB  - Z39Ig is a recently-identified gene with immunoglobulin-like domains whose
      function is unknown. We examined expression of Z39Ig in 1432 human cDNA
      libraries, and found it primarily in synovium of patients with rheumatoid
      arthritis, in placenta, and in lung. We analyzed its co-expression pattern using
      the Guilt-by-Association (GBA) algorithm, and found that it is most similar in
      expression to early genes in the classical complement system (C1qA, C1qB, C1qC,
      C1r, and C1 inhibitor), MHC class II genes (HLA-DR alpha, HLA-DR beta 1, and HLA
      DP alpha 1), Fc receptors (Fc gamma RIIa and Fc epsilon R1), lysosomal protein
      (LAPTm5), tissue transglutaminase, and macrophage receptors (MARCO and
      CD163/M130). The sequence and expression data suggest that Z39Ig is a cell
      surface receptor, expressed in activated macrophages, and linked with the
      classical complement system, most likely in phagocytosis preceding antigen
      presentation. Knowledge of this gene may contribute to better understanding of
      the role of complement and activated macrophages in rheumatoid arthritis and
      systemic lupus.

PMID- 11997109
TI  - Molecular cloning and characterization of a novel gene upregulated early during
      postnatal rat lung development.
AB  - Alveoli form, in part, by subdivision (septation) of saccules constituting the
      gas exchange region of the immature lung. Rat lungs septate from postnatal day 4
      through 14 but alveoli in male rats continue to form, by other means, until about
      age 44 days. In rats, we sought to identify genes involved in septation. Using
      differential display reverse transcription polymerase chain reaction, we cloned a
      cDNA, rA5D3, that had 1270 bp with an open reading frame encoding a putative
      polypeptide of 165 amino acids containing potential leucine zipper motifs and
      phosphorylation sites. Database searches indicated rA5D3 was a novel gene. rA5D3
      RNA relative concentration increased 1.7-fold between postnatal days 4 and 8,
      decreased 4-fold between days 8 and 14, declined significantly thereafter but was
      still detected post alveolus formation. If the expression of rA5D3 protein
      resembles its RNA, its peak (postnatal day 8) is well after the onset of
      septation, suggesting a role other than the initiation of septation.

PMID- 11997110
TI  - A second stress-inducible glutathione S-transferase gene from Schizosaccharomyces
      pombe.
AB  - A second glutathione S-transferase gene (GST II) was isolated from the
      chromosomal DNA of the fission yeast Schizosaccharomyces pombe. The nucleotide
      sequence determined contains 1908 bp including an open reading frame of 230 amino
      acids that would encode a protein of a molecular mass of 26843.4 Da. The amino
      acid sequence of the putative GST II is very homologous with that of the
      previously isolated GST gene (GST I) located in the same chromosome III of S.
      pombe. The cloned GST II gene produces the functional GST in S. pombe, and it
      gives much higher GST in the stationary phase than in the exponential phase.
      Regulation of the GST II gene was studied using the GST II-lacZ fusion. The
      synthesis of beta-galactosidase from the fusion plasmid is greatly enhanced by
      the treatments with oxidative stresses such as menadione and mercuric chloride.
      It is also induced by o-dinitrobenzene, one of the GST substrates. NO-generating
      S-nitroso-N-acetylpenicillamine has a weak induction effect on the expression of
      GST II gene. These results indicate that the S. pombe GST II gene is involved in
      the oxidative stress response and detoxification. However, physiological meaning
      on the existence of the two similar GST genes in S. pombe remains unknown yet.

PMID- 11997111
TI  - Cloning of murine cysteine sulfinic acid decarboxylase and its mRNA expression in
      murine tissues.
AB  - Cysteine sulfinic acid decarboxylase (CSD) is the rate-limiting enzyme for
      biosynthesis of taurine which is essential to biological processes such as
      development of the brain and eye, reproduction, osmoregulation as well as the
      anti-inflammatory activity of leukocytes. We report the cDNA sequence of murine
      CSD that predicts a polypeptide of 493 amino acids. This protein shares 98% and
      90% of amino acids with rat and human CSD, respectively, indicating that it is a
      true ortholog of CSD. Northern blot analysis revealed that CSD mRNA is expressed
      in kidney and liver, and was not detected in lymphoid tissues and lung. The
      nucleotide sequence of murine CSD should be useful for genetic manipulation of
      the CSD gene.

PMID- 11997112
TI  - Cloning and expression of a novel human galectin cDNA, predominantly expressed in
      placenta(1).
AB  - A novel human galectin cDNA (PPL13) was isolated by screening a human 18-week
      fetal brain library. The mRNA was predominantly expressed in placenta, while the
      expression of it was not or barely detectable in heart, brain, lung, liver,
      skeletal muscle, kidney, and pancreas by Northern blot. COS-7 cells transfected
      with cDNA encoding human PPL13 sequestered the protein in nuclei although it
      lacked any known nuclear localization signal. STS of Unigene Hs. 24236 placed the
      cDNA to human chromosome 19q13.2.

PMID- 11997113
TI  - A new method for the preparation of giant liposomes in high salt concentrations
      and growth of protein microcrystals in them.
AB  - We have developed a new method for the preparation of giant liposomes in aqueous
      solution containing high salt concentrations (up to 2.0 M). Hydrophilic polymers
      attached to the surface of lipid membranes by including a small amount of
      poly(ethylene glycol)-grafted phospholipid in the membrane increase the repulsive
      force between the membranes, which makes it possible to form giant liposomes at
      high ionic strength. Using this method, we could grow micron-sized (10-50 microm)
      protein crystals in a giant liposome. These results demonstrate that this method
      is a promising tool for the preparation of 'artificial cells' under various
      conditions.

PMID- 11997114
TI  - Effect of pH on the interfacial tension of bilayer lipid membrane formed from
      phosphatidylcholine or phosphatidylserine.
AB  - The effect of pH of an electrolyte solution on the interfacial tension of lipid
      membrane formed from phosphatidylcholine (PC) or phosphatidylserine (PS) was
      studied. The relationships were well described by an equation presented earlier
      based on the Gibbs isotherm but only in the proximity of the isoelectric point.
      Therefore, in this work models have been derived to describe the adsorption of
      the H(+) and OH(-) ions at lipid surfaces formed from PC or PS, which would
      reproduce changes in interfacial tension more correctly, particularly in the
      ranges distant from the isoelectric point. In one model, the surface is
      continuous with uniformly distributed functional groups constituting the centres
      of H(+) and OH(-) ion adsorption while in the other the surface is built of lipid
      molecules, free or with attached H(+) and OH(-) ions. In both models, the
      contributions of the individual lipid molecule forms to the interfacial tension
      of the bilayer were assumed to be additive.

PMID- 11997115
TI  - Biophysical consequences of linker chemistry and polymer size on stealth
      erythrocytes: size does matter.
AB  - Immunocamouflaged red blood cells (RBC) are produced by cell surface
      derivatization with methoxypolyethylene glycol (mPEG). These immunologically
      attenuated cells may reduce the risk of allosensitization in chronically
      transfused patients. To characterize the effects of differing linker chemistries
      and polymer lengths, RBC were modified with cyanuric chloride activated mPEG (C
      mPEG 5 kDa), benzotriazole carbonate methoxyPEG (BTC-mPEG; 5 or 20 kDa) or N
      hydroxysuccinimidyl ester of mPEG propionic acid (SPA-mPEG; 2, 5 or 20 kDa).
      Biophysical methods including particle electrophoresis and aqueous two-phase
      polymer partitioning were employed to compare the PEG derivatives. While C-mPEG
      was faster reacting, both BTC-mPEG and SPA-mPEG gave comparable findings after 1
      h. Both PEG surface density and molecular mass had a large effect on RBC surface
      properties. Proportional changes in electrophoretic mobility and preferential
      phase partitioning were achieved by increasing either the quantity of surface PEG
      or the PEG molecular mass. In addition, two-phase partitioning may provide a
      means for efficiently removing unmodified or lightly modified (hence potentially
      immunogenic) RBC in the clinical setting. Furthermore, mPEG modification
      significantly inhibits cell-cell interaction as evidenced by loss of Rouleaux
      formation and, consequently, sedimentation rate. Importantly, BTC-mPEG 20 kDa RBC
      showed normal in vivo survival in mice at immunoprotective concentrations (up to
      2 mM).

PMID- 11997116
TI  - Conformational changes of colicin Ia channel-forming domain upon membrane
      binding: a solid-state NMR study.
AB  - Channel-forming colicins are bactericidal proteins that spontaneously insert into
      hydrophobic lipid bilayers. We have used magic-angle spinning solid-state nuclear
      magnetic resonance spectroscopy to examine the conformational differences between
      the water-soluble and the membrane-bound states of colicin Ia channel domain, and
      to study the effect of bound colicin on lipid bilayer structure and dynamics. We
      detected (13)C and (15)N isotropic chemical shift differences between the two
      forms of the protein, which indicate structural changes of the protein due to
      membrane binding. The Val C(alpha) signal, unambiguously assigned by double
      quantum experiments, gave a 0.6 ppm downfield shift in the isotropic position and
      a 4 ppm reduction in the anisotropic chemical shift span after membrane binding.
      These suggest that the alpha-helices in the membrane-bound colicin adopt more
      ideal helical torsion angles as they spread onto the membrane. Colicin binding
      significantly reduced the lipid chain order, as manifested by (2)H quadrupolar
      couplings. These results are consistent with the model that colicin Ia channel
      domain forms an extended helical array at the membrane-water interface upon
      membrane binding.

PMID- 11997117
TI  - Amino acid and divalent ion permeability of the pores formed by the Bacillus
      thuringiensis toxins Cry1Aa and Cry1Ac in insect midgut brush border membrane
      vesicles.
AB  - The pores formed by Bacillus thuringiensis insecticidal toxins have been shown to
      allow the diffusion of a variety of monovalent cations and anions and neutral
      solutes. To further characterize their ion selectivity, membrane permeability
      induced by Cry1Aa and Cry1Ac to amino acids (Asp, Glu, Ser, Leu, His, Lys and
      Arg) and to divalent cations (Mg(2+), Ca(2+) and Ba(2+)) and anions (SO(4)(2-)
      and phosphate) was analyzed at pH 7.5 and 10.5 with midgut brush border membrane
      vesicles isolated from Manduca sexta and an osmotic swelling assay. Shifting pH
      from 7.5 to 10.5 increases the proportion of the more negatively charged species
      of amino acids and phosphate ions. All amino acids diffused well across the toxin
      induced pores, but, except for aspartate and glutamate, amino acid permeability
      was lower at the higher pH. In the presence of either toxin, membrane
      permeability was higher for the chloride salts of divalent cations than for the
      potassium salts of divalent anions. These results clearly indicate that the pores
      are cation-selective.

PMID- 11997118
TI  - Expression and promoter analysis of SLC19A2 in the human intestine.
AB  - The molecular mechanism and regulation of the intestinal uptake process of
      dietary thiamine is not well understood. Previous studies have established the
      involvement of a carrier-mediated system for thiamine uptake in the human
      intestine. Recently a human thiamine transporter, SLC19A2, was cloned from a
      number of human tissues. Little, however, is known about expression of the
      SLC19A2 message along the native human gastrointestinal tract, and no analysis of
      its promoter in intestinal tissue is available. Therefore, the current studies
      were aimed at investigating the expression of SLC19A2 in the human
      gastrointestinal tract and at analyzing the promoter of this potential intestinal
      thiamine transporter. First we cloned SLC19A2 cDNA from a human intestinal cell
      line (Caco-2) by reverse transcriptase-polymerase chain reaction, then used this
      cDNA as a probe in Northern blot analysis. SLC19A2 message was found to be
      expressed in all gastrointestinal tissues in the following order:
      liver>stomach>duodenum>jejunum>colon>cecum>rectum>ileum. SLC19A2 was also
      expressed at the protein level in Caco-2 cells and in native human small
      intestine by Western blot analysis. We also cloned the 5'-regulatory region of
      the SLC19A2 gene and confirmed activity of its promoter following transfection
      into intestinal epithelial Caco-2 cells. Furthermore, we identified the minimal
      promoter region required for basal activity of SLC19A2 in these cells which was
      found to be mainly encoded in a sequence between -356 and -36, and included
      multiple cis-regulatory elements. Transcription initiation sites of the SLC19A2
      gene in intestinal epithelial Caco-2 cells were also identified by 5'-rapid
      amplification of cDNA ends. These results demonstrate that SLC19A2 is expressed
      in various regions of the human gastrointestinal tract. In addition, the results
      provide the first characterization of the SLC19A2 promoter. These findings raise
      the possibility that SLC19A2 may play a role in the normal intestinal thiamine
      absorption process.

PMID- 11997119
TI  - Improved retention of idarubicin after intravenous injection obtained for
      cholesterol-free liposomes.
AB  - To date there has been a focus on the application of sterically stabilized
      liposomes, composed of saturated diacylphospholipid, polyethylene glycol (PEG)
      conjugated lipids (5-10 mole%) and cholesterol (CH) (>30 mole%), for the systemic
      delivery of drugs. However, we are now exploring the utility of liposome
      formulations composed of diacylphospholipid conjugated PEG mixtures prepared in
      the absence of added cholesterol, with the primary objective of developing
      formulations that retain encapsulated drug better than comparable formulations
      prepared with cholesterol. In this report the stability of cholesterol-free
      distearoylphosphatidylcholine (DSPC):distearoylphosphatidylethanolamine (DSPE)
      PEG(2000) (95:5 mol/mol) liposomes was characterized in comparison to cholesterol
      containing formulations DSPC:CH (55:45 mol/mol) and DSPC:CH:DSPE-PEG(2000)
      (50:45:5 mol/mol/mol), in vivo. Circulation longevity of these formulations was
      determined in consideration of variables that included varying phospholipid acyl
      chain length, PEG content and molecular weight. The application of cholesterol
      free liposomes as carriers for the hydrophobic anthracycline antibiotic,
      idarubicin (IDA), was assessed. IDA was encapsulated using a transmembrane pH
      gradient driven process. To determine stability in vivo, pharmacokinetic studies
      were performed using 'empty' and drug-loaded [(3)H]cholesteryl hexadecyl ether
      radiolabeled liposomes administered intravenously to Balb/c mice. Inclusion of 5
      mole% of DSPE-PEG(2000) or 45 mole% cholesterol to DSPC liposomes increased the
      mean plasma area under the curve (AUC(0-24h)) 19-fold and 10-fold, respectively.
      Cryo-transmission electron micrographs of IDA loaded liposomes indicated that the
      drug formed a precipitate within liposomes. The mean AUC(0-4h) for free IDA was
      0.030 micromole h/ml as compared to 1.38 micromole h/ml determined for the
      DSPC:DSPE-PEG(2000) formulation, a 45-fold increase, demonstrating that IDA was
      retained better in cholesterol-free compared to cholesterol-containing liposomes.

PMID- 11997120
TI  - Characterisation and cloning of a Na(+)-dependent broad-specificity neutral amino
      acid transporter from NBL-1 cells: a novel member of the ASC/B(0) transporter
      family.
AB  - Na(+)-dependent neutral amino acid transport into the bovine renal epithelial
      cell line NBL-1 is catalysed by a broad-specificity transporter originally termed
      System B(0). This transporter is shown to differ in specificity from the B(0)
      transporter cloned from JAR cells [J. Biol. Chem. 271 (1996) 18657] in that it
      interacts much more strongly with phenylalanine. Using probes designed to
      conserved transmembrane regions of the ASC/B(0) transporter family we have
      isolated a cDNA encoding the NBL-1 cell System B(0) transporter. When expressed
      in Xenopus oocytes the clone catalysed Na(+)-dependent alanine uptake which was
      inhibited by glutamine, leucine and phenylalanine. However, the clone did not
      catalyse Na(+)-dependent phenylalanine transport, again as in NBL-1 cells. The
      clone encoded a protein of 539 amino acids; the predicted transmembrane domains
      were almost identical in sequence to those of the other members of the B(0)/ASC
      transporter family. Comparison of the sequences of NBL-1 and JAR cell
      transporters showed some differences near the N-terminus, C-terminus and in the
      loop between helices 3 and 4. The NBL-1 B(0) transporter is not the same as the
      renal brush border membrane transporter since it does not transport
      phenylalanine. Differences in specificity in this protein family arise from
      relatively small differences in amino acid sequence.

PMID- 11997121
TI  - Enhanced gene delivery in vitro and in vivo by improved transferrin-lipoplexes.
AB  - Cationic liposomes and the complexes they form with DNA (lipoplexes) constitute
      the most promising alternative to the use of viral vectors for gene therapy. One
      of the limitations to their application in vivo, however, is the inhibition of
      gene delivery by serum. In a previous study, we demonstrated that transferrin
      (Tf)-lipoplexes were superior to plain lipoplexes in transfecting HeLa cells in
      the presence of high concentrations of serum. With the goal of obtaining
      efficient gene expression in vivo, we evaluated the efficacy of Tf-lipoplexes
      (containing DOTAP and cholesterol) in transfecting primary hepatocytes and
      adipocytes in the presence of high serum concentrations. The association of
      transferrin with cationic liposomes increased luciferase expression compared to
      plain lipoplexes in primary cells as well as in HepG2 and 3T3-L1 differentiated
      adipocytes. The complexes were not cytotoxic and were highly effective in
      protecting DNA from attack by DNase I. An efficient and reliable method was
      developed to prepare lipoplexes containing both Tf and protamine sulfate, where
      the latter was mixed with transferrin, followed by the addition of cationic
      liposomes and DNA. The resulting protamine-Tf-lipoplexes increased significantly
      the levels of gene expression in cultured cells and in various tissues in mice
      following i.v. administration.

PMID- 11997122
TI  - Programmable chronopotentiometry as a tool for the study of electroporation and
      resealing of pores in bilayer lipid membranes.
AB  - This paper presents the application of chronopotentiometry in the study of
      membrane electroporation. Chronopotentiometry with a programmable current
      intensity was used. The experiments were performed on planar bilayer
      phosphatidylcholine and cholesterol membranes formed by the Mueller-Rudin method.
      It was demonstrated that a constant-intensity current flow through the bilayer
      membranes generated voltage fluctuations during electroporation. These
      fluctuations (following an increase and decrease in membrane conductance) were
      interpreted as a result of the opening and closing of pores in membrane
      structures. The decrease in membrane potential to zero did not cause the pore to
      close immediately. The pore was maintained for about 200 s. The closing of the
      pore and recovery of the continuous structure of the membrane proceeded not only
      when the membrane potential equalled zero, but also at membrane potentials up to
      several tens of millivolts. The fluctuations of the pore were possible at values
      of membrane potential in the order of at least 100 mV. The size of the pore
      changed slightly and it closed after some time below this potential value.

PMID- 11997123
TI  - Functional importance of calcium binding sites in outer membrane phospholipase A.
AB  - Outer membrane phospholipase A (OMPLA) is an integral membrane enzyme that
      hydrolyses phospholipids requiring Ca(2+) as cofactor. In vitro studies have
      shown that OMPLA is only active as a dimer. The structures of monomeric and
      dimeric OMPLA provided possible clues to the activation process. In the inhibited
      dimeric species calcium ions are located at the dimer interface ideally suited to
      stabilise the oxyanion intermediates formed during catalysis. The side chain
      hydroxyl function of Ser152 is one of the ligands of this interfacial calcium. In
      the crystal structure of monomeric OMPLA the interfacial calcium site is lacking,
      but calcium was found to bind at a site involving the carboxylates of Asp149 and
      Asp184. In the current study the relevance of the identified calcium sites has
      been studied by site-directed mutagenesis. The Ser152Asn variant confirmed the
      importance of the interfacial calcium site for catalysis, and also demonstrated
      that this site is essentially involved in the dimerisation process. Replacements
      of the ligands in monomeric OMPLA, i.e. Asp149Asn, Asp149Ala and Asp184Asn, only
      showed minor effects on catalytic activity and dimerisation. A stronger effect
      observed for the variant Asp184Ala was explained by the proximity of Asp184 to
      the catalytically important Ser152 residue. We propose that Asp149 and Asp184
      provide an electronegative funnel that may facilitate Ca(2+) transfer to the
      interfacial calcium site.

PMID- 11997124
TI  - Compositional domain immiscibility in whole myelin monolayers at the air-water
      interface and Langmuir-Blodgett films.
AB  - Monomolecular layers of whole myelin membrane can be formed at the air-water
      interface from vesicles or from solvent solution of myelin. The films appear
      microheterogeneous as seen by epifluorescence and Brewster angle microscopy. The
      pattern consists mainly of two coexisting liquid phases over the whole
      compression isotherm. The liquid nature of the phases is apparent from the
      fluorescent probe behavior, domain mobility, deformability and boundary
      relaxation due to the line tension of the surface domains. The monolayers were
      transferred to alkylated glass and fluorescently labeled against myelin
      components. The immunolabeling of two major proteins of myelin (myelin basic
      protein, proteolipid-DM20) and of 2',3'-cyclic nucleotide 3'-phosphodiesterase
      shows colocalization with probes partitioning preferentially in liquid-expanded
      lipid domains also containing ganglioside G(M1). A different phase showing an
      enrichment in cholesterol, galactocerebroside and phosphatidylserine markers is
      also found. The distribution of components is qualitatively independent of the
      lateral surface pressure and is generally constituted by one phase enriched in
      charged components in an expanded state coexisting with another phase enriched in
      non-charged constituents of lower compressibility. The domain immiscibility
      provides a physical basis for the microheterogeneity found in this membrane model
      system.

PMID- 11997125
TI  - Differential thermal effects on the energy distribution between photosystem II
      and photosystem I in thylakoid membranes of a psychrophilic and a mesophilic
      alga.
AB  - Sensitivity of the photosynthetic thylakoid membranes to thermal stress was
      investigated in the psychrophilic Antarctic alga Chlamydomonas subcaudata. C.
      subcaudata thylakoids exhibited an elevated heat sensitivity as indicated by a
      temperature-induced rise in F(o) fluorescence in comparison with the mesophilic
      species, Chlamydomonas reinhardtii. This was accompanied by a loss of structural
      stability of the photosystem (PS) II core complex and functional changes at the
      level of PSI in C. reinhardtii, but not in C. subcaudata. Lastly, C. subcaudata
      exhibited an increase in unsaturated fatty acid content of membrane lipids in
      combination with unique fatty acid species. The relationship between lipid
      unsaturation and the functioning of the photosynthetic apparatus under elevated
      temperatures is discussed.

PMID- 11997126
TI  - Flash-induced turnover of the cytochrome bc1 complex in chromatophores of
      Rhodobacter capsulatus: binding of Zn2+ decelerates likewise the oxidation of
      cytochrome b, the reduction of cytochrome c1 and the voltage generation.
AB  - The effect of Zn2+ on the rates of electron transfer and of voltage generation in
      the cytochrome bc1 complex (bc1) was investigated under excitation of Rhodobacter
      capsulatus chromatophores with flashing light. When added, Zn2+ retarded the
      oxidation of cytochrome b and allowed to monitor (at 561-570 nm) the reduction of
      its high potential heme b(h) (in the absence of Zn2+ this reaction was masked by
      the fast re-oxidation of the heme). The effect was accompanied by the
      deceleration of both the cytochrome c(1) reduction (as monitored at 552-570 nm)
      and the generation of transmembrane voltage (monitored by electrochromism at 522
      nm). At Zn2+ <100 microM the reduction of heme b(h) remained 10 times faster than
      other reactions. The kinetic discrepancy was observed even after an attenuated
      flash, when bc1 turned over only once. These observations (1) raise doubt on the
      notion that the transmembrane electron transfer towards heme b(h) is the main
      electrogenic reaction in the cytochrome bc1 complex, (2) imply an allosteric link
      between the site of heme b(h) oxidation and the site of cytochrome c1 reduction
      at the opposite side of the membrane, and (3) indicate that the internal
      redistribution of protons might account for the voltage generation by the
      cytochrome bc1 complex.

PMID- 11997127
TI  - Change in electron and spin density upon electron transfer to haem.
AB  - Haems are the cofactors of cytochromes and important catalysts of biological
      electron transfer. They are composed of a planar porphyrin structure with iron
      coordinated at the centre. It is known from spectroscopy that ferric low-spin
      haem has one unpaired electron at the iron, and that this spin is paired as the
      haem receives an electron upon reduction (I. Bertini, C. Luchinat, NMR of
      Paramagnetic Molecules in Biological Systems, Benjamin/Cummins Publ. Co., Menlo
      Park, CA, 1986, pp. 165-170; H.M. Goff, in: A.B.P. Lever, H.B. Gray (Eds.), Iron
      Porphyrins, Part I, Addison-Wesley Publ. Co., Reading, MA, 1983, pp. 237-281; G.
      Palmer, in: A.B.P. Lever, H.B. Gray (Eds.), Iron Porphyrins, Part II, Addison
      Wesley Publ. Co., Reading, MA, 1983, pp. 43-88). Here we show by quantum chemical
      calculations on a haem a model that upon reduction the spin pairing at the iron
      is accompanied by effective delocalisation of electrons from the iron towards the
      periphery of the porphyrin ring, including its substituents. The change of charge
      of the iron atom is only approx. 0.1 electrons, despite the unit difference in
      formal oxidation state. Extensive charge delocalisation on reduction is important
      in order for the haem to be accommodated in the low dielectric of a protein, and
      may have impact on the distance dependence of the rates of electron transfer. The
      lost individuality of the electron added to the haem on reduction is another
      example of the importance of quantum mechanical effects in biological systems.

PMID- 11997128
TI  - The molecular mechanism of ATP synthesis by F1F0-ATP synthase.
AB  - ATP synthesis by oxidative phosphorylation and photophosphorylation, catalyzed by
      F1F0-ATP synthase, is the fundamental means of cell energy production. Earlier
      mutagenesis studies had gone some way to describing the mechanism. More recently,
      several X-ray structures at atomic resolution have pictured the catalytic sites,
      and real-time video recordings of subunit rotation have left no doubt of the
      nature of energy coupling between the transmembrane proton gradient and the
      catalytic sites in this extraordinary molecular motor. Nonetheless, the molecular
      events that are required to accomplish the chemical synthesis of ATP remain
      undefined. In this review we summarize current state of knowledge and present a
      hypothesis for the molecular mechanism of ATP synthesis.

PMID- 11997129
TI  - Density functional calculations modelling tyrosine oxidation in oxygenic
      photosynthetic electron transfer.
AB  - Hybrid density functional calculations are used to model tyrosine oxidation
      during electron transfer reactions of photosystem II. The predicted frequency
      values for the 7a and deltaCOH modes of the reduced form and the 7a mode of the
      oxidised radical form are in excellent agreement with experimental data obtained
      for Mn and Ca depleted systems by Hienerwadel et al. [Biochemistry 36 (1997)
      15447] and Berthomieu et al. [Biochemistry 37 (1998) 10547]. The calculations
      confirm that the two tyrosines Y(D) and Y(Z) are protonated in the reduced form.
      On oxidation the larger 7a frequency value observed experimentally for Y(Z*) can
      be best explained by a greater localisation of the protonic charge released on
      formation of this tyrosyl free radical.

PMID- 11997130
TI  - A theoretical approach to the link between oxidoreductions and pyrite formation
      in the early stage of evolution.
AB  - There are two fundamental axioms of surface metabolism theory: (i) pyrite
      formation from H2S and FeS is proposed as a source of energy for life, and (ii)
      archaic reductive citric acid cycle is put into the center of a metabolic
      network. However, the concept fails to indicate how sulfide oxidation ought to be
      coupled to processes driven by free energy change occurring during pyrite
      production, and secondly, how reductive citric acid cycle ought to be supplied
      with row material(s). Recently, the non-enzymatic methylglyoxalase pathway has
      been recommended as the anaplerotic route for the reductive citric acid cycle. In
      this paper a mechanism is proposed by which the oxidation of lactate, the
      essential step of the anaplerotic path, becomes possible and a coupling system
      between sulfide oxidation and endergonic reaction(s) is also presented.
      Oxidoreduction for other redox pairs is discussed too. It is concluded that the
      S(o)/H2S system may have been the clue to energy production at the early stage of
      evolution, as hydrogen sulfide produced by the metabolic network may have
      functioned as a coupling molecule between endergonic and exergonic reactions.

PMID- 11997131
TI  - Metabolic underpinnings of the paradoxical net phosphocreatine resynthesis in
      contracting rat gastrocnemius muscle.
AB  - Net phosphocreatine (PCr) resynthesis during muscle contraction is a paradoxical
      phenomenon because it occurs under conditions of high energy demand. The
      metabolic underpinnings of this phenomenon were analyzed non-invasively using 31P
      magnetic resonance spectroscopy in rat gastrocnemius muscle (n=11) electrically
      stimulated (7.6 Hz, 6 min duration) in situ under ischemic and normoxic
      conditions. During ischemic stimulation, [PCr] initially fell to a steady state
      (9+/-5% of resting concentration) which was maintained for the last 5 min of
      stimulation, whereas isometric force production decreased to a non-measurable
      level beyond 3 min. Throughout normoxic stimulation, [PCr] and force production
      declined to a steady state after respectively 1 min (5+/-3% of resting
      concentration) and 3.25 min (21+/-8% of initial value) of stimulation. Contrary
      to the observations under ischemia, a paradoxical net PCr resynthesis was
      recorded during the last 2 min of normoxic stimulation and was not accompanied by
      any improvement in force production. These results demonstrate that the
      paradoxical net PCr resynthesis recorded in contracting muscle relies exclusively
      on oxidative energy production and could occur in inactivated fibers, similarly
      to PCr resynthesis during post-exercise recovery.

PMID- 11997132
TI  - Effects of cold exposure in vivo and uncouplers and recouplers in vitro on potato
      tuber mitochondria.
AB  - Effects of cold exposure in vivo and treatment with laurate, carboxyatractylate,
      atractylate, nucleotides, and BSA in vitro on potato tuber mitochondria have been
      studied. Cold exposure of tubers for 48-96 h resulted in some uncoupling that
      could be reversed completely by BSA and partially by ADP, ATP, UDP,
      carboxyatractylate, and atractylate. UDP was less effective than ADP and ATP, and
      atractylate was less effective than carboxyatractylate. The recoupling effects of
      nucleotides were absent when the nucleotides were added after carboxyatractylate.
      GDP, UDP, and CDP did not recouple mitochondria from either the control or the
      cold-exposed tubers. This indicates that the cold-induced fatty acid-mediated
      uncoupling in potato tuber mitochondria is partially due to the operation of the
      ATP/ADP antiporter. As to the plant uncoupling protein, its contribution to the
      uncoupling in tuber is negligible or, under the conditions used, somehow
      desensitized to nucleotides.

PMID- 11997133
TI  - 3-O-methylfluorescein phosphate as a fluorescent substrate for plasma membrane
      Ca2+-ATPase.
AB  - 3-O-methylfluorescein phosphate hydrolysis, catalyzed by purified erythrocyte
      Ca2+-ATPase in the absence of Ca2+, was slow in the basal state, activated by
      phosphatidylserine and controlled proteolysis, but not by calmodulin. p
      Nitrophenyl phosphate competitively inhibits hydrolysis in the absence of Ca2+,
      while ATP inhibits it with a complex kinetics showing a high and a low affinity
      site for ATP. Labeling with fluorescein isothiocyanate impairs the high affinity
      binding of ATP, but does not appreciably modify the binding of any of the
      pseudosubstrates. In the presence of calmodulin, an increase in the Ca2+
      concentration produces a bell-shaped curve with a maximum at 50 microM Ca2+. At
      optimal Ca2+ concentration, hydrolysis of 3-O-methylfluorescein phosphate
      proceeds in the presence of fluorescein isothiocyanate, is competitively
      inhibited by p-nitrophenyl phosphate and, in contrast to the result observed in
      the absence of Ca2+, it is activated by calmodulin. In marked contrast with other
      pseudosubstrates, hydrolysis of 3-O-methylfluorescein phosphate supports Ca2+
      transport. This highly specific activity can be used as a continuous fluorescent
      marker or as a tool to evaluate partial steps from the reaction cycle of plasma
      membrane Ca2+-ATPases.

PMID- 11997134
TI  - Control of oxidative phosphorylation by Complex I in rat liver mitochondria:
      implications for aging.
AB  - We compared NAD-dependent state 4 and state 3 respiration, NADH oxidation and
      Complex I specific activity in liver mitochondria from 4- and 30-month-old rats.
      All the activities examined were significantly decreased with aging. In both
      groups of animals, the flux control coefficients measured by rotenone titration
      indicated that Complex I is largely rate controlling upon NADH aerobic oxidation
      while, in state 3 respiration, it shares the control with other steps in the
      pathway. Moreover, we observed a trend wherein flux control coefficients of
      Complex I became higher with age. This indication was strengthened by examining
      the rotenone inhibition thresholds showing that Complex I becomes more rate
      controlling, over all the examined activities, during aging. Our results point
      out that age-related alterations of the mitochondrial functions are also present
      in tissues considered less prone to accumulate mitochondrial DNA mutations.

PMID- 11997135
TI  - Heart design: free ADP scales with absolute mitochondrial and myofibrillar
      volumes from mouse to human.
AB  - Our aim was to estimate a number of bioenergetic parameters in the beating mouse,
      rat and guinea pig heart in situ and compare the values to those in hearts of
      mammals over a 2000-fold range in body mass. For the mouse, rat and guinea pig
      heart, we report a phosphorylation ratio of 1005+/-50 (n=16), 460+/-32 (n=10) and
      330+/-22 (n=5) mM(-1) and a free cytosolic [ADP] concentration of 13, 18 and 22
      microM, respectively. When each parameter was plotted against body mass, they
      scaled closely to the quarter power (-0.28, r=0.99 and -0.23, r=0.97). A similar
      regression slope was found when the inverse of free [ADP] was plotted against
      absolute mitochondrial (slope=-0.26, r=0.99) and myofibrillar volumes (slope=
      0.24, r=0.99). The similar slopes indicate that the ratio of absolute
      mitochondria and myofibrillar volumes in the healthy mammalian heart is a
      constant, and independent of body size. In conclusion, our study supports the
      hypothesis that the mammalian heart has a number of highly conserved
      thermodynamic and kinetic parameters that obey quarter-power laws linking the
      phosphorylation ratio, ATP turnover rates, free [ADP] and absolute mitochondrial
      volumes to body size. The results are discussed in terms of possible mechanisms
      and potential deviations from these laws in some disease states.

PMID- 11997136
TI  - Interaction of purified NDH-1 from Escherichia coli with ubiquinone analogues.
AB  - The NADH:ubiquinone oxidoreductase (NDH-1 or Complex I) of Escherichia coli is a
      smaller version of the mitochondrial enzyme, being composed of 13 protein
      subunits in comparison to the 43 of bovine heart complex I. The bacterial NDH-1
      from an NDH-2-deficient strain was purified using a combination of anion exchange
      chromatography and sucrose gradient centrifugation. All 13 different subunits
      were detected in the purified enzyme by either N-terminal sequencing or matrix
      assisted laser desorption/ionization time-of-flight mass spectral analysis. In
      addition, some minor contaminants were observed and identified. The activity of
      the enzyme was studied and the effects of phospholipid and dodecyl maltoside were
      characterized. Kinetic analyses were performed for the enzyme in the native
      membrane as well as for the purified NDH-1, using ubiquinone-1, ubiquinone-2 or
      decylubiquinone as the electron acceptors. The purified enzyme exhibited between
      1.5- and 4-fold increase in the apparent K(m) for these acceptors. Both
      ubiquinone-2 and decylubiquinone are good acceptors for this enzyme, while
      affinity of NDH-1 for ubiquinone-1 is clearly lower than for the other two,
      particularly in the purified state.

PMID- 11997137
TI  - Interference of an apcA insertion with complementary chromatic adaptation in the
      diazotrophic Synechocystis sp. strain BO 8402.
AB  - Complementary chromatic adaptation was studied in two unicellular diazotrophic
      Synechocystis-type cyanobacteria, strains BO 8402 and BO 9201. Strain BO 8402 was
      isolated from Lake Constance as a mutant lacking phycobilisomes due to an
      insertion sequence element in the gene apcA, encoding alpha-allophycocyanin.
      Strain BO 9201 recovered the ability to assemble functional phycobilisomes after
      a spontaneous excision of the insertion sequence element in apcA. Simultaneously,
      the strain became able to perform group II complementary chromatic adaptation by
      regulating the synthesis of phycoerythrin. The two strains had identical
      phycoerythrin operons, cpeBA, and similar-sized transcripts were formed upon
      induction by green light. However, in strain BO 8402 the cpeBA transcript level
      was approx. 20-fold lower than in strain BO 9201. Because strain BO 8402 cannot
      synthesize allophycocyanin and phycocyanin is sequestered in paracrystalline
      inclusion bodies, non-assembled phycoerythrin may accumulate inside the cells. It
      was examined whether non-assembled phycoerythrin or other effects caused by the
      absence of phycobilisomes, such as a permanently oxidized redox status of the
      photosynthetic electron transport chain or a distorted ratio of C and N
      assimilation mediated the repression of cpeBA transcription in strain BO 8402. No
      such links could be established. We therefore concluded that in these
      diazotrophic Synechocystis-type cyanobacteria the green light-induced
      transcription of the cpe operon directly required a functional apc operon.

PMID- 11997138
TI  - pH dependent inactivation of solubilized F1F0 ATP synthase by
      dicyclohexylcarbodiimide: pK(a) of detergent unmasked aspartyl-61 in Escherichia
      coli subunit c.
AB  - The pH dependence of the reaction of dicyclohexylcarbodiimide with the essential
      aspartyl-61 residue in subunit c of Escherichia coli ATP synthase was compared in
      membranes and in a detergent dispersed preparation of the enzyme. The rate of
      reaction was estimated by measuring the inactivation of ATPase activity. The
      reaction with the detergent dispersed form of the enzyme proved to be pH
      sensitive with the essential aspartyl group titrating with a pK(a)=8. However,
      when measured with E. coli membranes, the reaction proved to be pH insensitive.
      The results suggest that the reacting aspartyl-61 residues are shielded from the
      bulk aqueous solvent when in the membrane, but then become aqueous-accessible
      following detergent solubilization.

PMID- 11997139
TI  - The rate of charge recombination in Photosystem II.
AB  - Loss by recombination of the charge separated state P(680+)Q(A-) limits the
      performance of Photosystem II (PS II) as a photochemical energy converter. Time
      constants reported in literature for this process are mostly either near 0.17 ms
      or near 1.4 ms. The shorter time is found in plant PS II when reduction of
      P(680+) by the secondary electron donor Tyrosine Z cannot occur because Y(Z) is
      already oxidized. The 1.4 ms recombination is seen in Y(Z)-less mutants of the
      cyanobacterium Synechocystis. However, the rate of P(680+)Q(A-) recombination
      that actually competes with the stabilization of the charge separation has not
      been previously reported. We have measured the kinetics of the flash-induced
      fluorescence yield changes in the microsecond time domain in Tris-washed spinach
      chloroplasts. In this way the kinetics and yield of P(680+) reduction by Y(Z)
      were obtained, and the rate of the competing P(680+)Q(A-) recombination could be
      evaluated. The recombination time was less than 0.5 ms; the best-fitting time
      constant was 0.1 ms. The presence of Y(Z)(ox) slightly decreased the efficiency
      of excitation trapping but did not seem to accelerate P(680+)Q(A-) recombination.
      The two P(680+)Q(A-) lifetimes in the literature probably reflect a significant
      difference between plant and cyanobacterial PS II.

PMID- 11997140
TI  - Xanthophyll biosynthetic mutants of Arabidopsis thaliana: altered
      nonphotochemical quenching of chlorophyll fluorescence is due to changes in
      Photosystem II antenna size and stability.
AB  - Xanthophylls (oxygen derivatives of carotenes) are essential components of the
      plant photosynthetic apparatus. Lutein, the most abundant xanthophyll, is
      attached primarily to the bulk antenna complex, light-harvesting complex (LHC)
      II. We have used mutations in Arabidopsis thaliana that selectively eliminate
      (and substitute) specific xanthophylls in order to study their function(s) in
      vivo. These include two lutein-deficient mutants, lut1 and lut2, the epoxy
      xanthophyll-deficient aba1 mutant and the lut2aba1 double mutant. Photosystem
      stoichiometry, antenna sizes and xanthophyll cycle activity have been related to
      alterations in nonphotochemical quenching of chlorophyll fluorescence (NPQ).
      Nondenaturing polyacrylamide gel electrophoresis indicates reduced stability of
      trimeric LHC II in the absence of lutein (and/or epoxy xanthophylls). Photosystem
      (antenna) size and stoichiometry is altered in all mutants relative to wild type
      (WT). Maximal DeltapH-dependent NPQ (qE) is reduced in the following order:
      WT>aba1>lut1 approximately lut2>lut2aba1, paralleling reduction in Photosystem
      (PS) II antenna size. Finally, light-activation of NPQ shows that zeaxanthin and
      antheraxanthin present constitutively in lut mutants are not qE active, and
      hence, the same can be inferred of the lutein they replace. Thus, a direct
      involvement of lutein in the mechanism of qE is unlikely. Rather, altered NPQ in
      xanthophyll biosynthetic mutants is explained by disturbed macro-organization of
      LHC II and reduced PS II-antenna size in the absence of the optimal, wild-type
      xanthophyll composition. These data suggest the evolutionary conservation of
      lutein content in plants was selected for due to its unique ability to optimize
      antenna structure, stability and macro-organization for efficient regulation of
      light-harvesting under natural environmental conditions.

PMID- 11997141
TI  - Rapid-scan Fourier transform infrared spectroscopy shows coupling of GLu-L212
      protonation and electron transfer to Q(B) in Rhodobacter sphaeroides reaction
      centers.
AB  - Rapid-scan Fourier transform infrared (FTIR) difference spectroscopy was used to
      investigate the electron transfer reaction Q(A-)Q(B)-->Q(A)Q(B-) (k(AB)(1)) in
      mutant reaction centers of Rhodobacter sphaeroides, where Asp-L210 and/or Asp-M17
      have been replaced with Asn. Mutation of both residues decreases drastically
      k(AB)(1)), attributed to slow proton transfer to Glu-L212, which becomes rate
      limiting for electron transfer to Q(B) [M.L. Paddock et al., Biochemistry 40
      (2001) 6893]. In the double mutant, the FTIR difference spectrum recorded during
      the time window 4-29 ms following a flash showed peaks at 1670 (-), 1601 (-) and
      1467 (+) cm(-1), characteristic of Q(A) reduction. The time evolution of the
      spectra shows reoxidation of Q(A-) and concomitant reduction of Q(B) with a
      kinetics of about 40 ms. In native reaction centers and in both single mutants,
      formation of Q(B-) occurs much faster than in the double mutant. Within the time
      resolution of the technique, protonation of Glu-L212, as characterized by an
      absorption increase at 1728 cm(-1) [E. Nabedryk et al., Biochemistry 34 (1995)
      14722], was found to proceed with the same kinetics as reduction of Q(B) in all
      samples. These rapid-scan FTIR results support the model of proton uptake being
      rate limiting for the first electron transfer from Q(A-) to Q(B) and the
      identification of Glu-L212 as the main proton acceptor in the state Q(A)Q(B-).

PMID- 11997142
TI  - Sequence and functional similarities between pro-apoptotic Bid and plant lipid
      transfer proteins.
AB  - Pro-apoptotic proteins of the Bcl-2 family are known to act on mitochondria and
      facilitate the release of cytochrome c, but the biochemical mechanism of this
      action is unknown. Association with mitochondrial membranes is likely to be
      important in determining the capacity of releasing cytochrome c. The present work
      provides new evidence suggesting that some pro-apoptotic proteins like Bid have
      an intrinsic capacity of binding and exchanging membrane lipids. Detailed
      analysis indicates a significant sequence similarity between a subset of Bcl-2
      family proteins including Bid and Nix and plant lipid transfer proteins. The
      similar structural signatures could be related to common interactions with
      membrane lipids. Indeed, isolated Bid shows a lipid transfer activity that is
      even higher than that of plant lipid transfer proteins. To investigate the
      possible relevance of these structure-function correlations to the apoptotic
      action of Bid, cell free assays were established with isolated mitochondria,
      recombinant Bid and a variety of exogenous lipids. Micromolar concentrations of
      lysolipids such as lysophosphatidylcholine were found to change the association
      of Bid with mitochondria and also stimulate the release of cytochrome c promoted
      by Bid. The changes in mitochondrial association and cytochrome c release were
      enhanced by the presence of liposomes of lipid composition similar to that of
      mitochondrial membranes. Thus, a mixture of liposomes, mitochondria and key
      lysolipids could reproduce the conditions enabling Bid to transfer lipids between
      donor and acceptor membranes, and also change its reversible association with
      mitochondria. Bid was also found to enhance the incorporation of a fluorescent
      lysolipid, but not of a related fatty acid, into mitochondria. On the basis of
      the results presented here, it is hypothesised that Bid action may depend upon
      its capacity of exchanging lipids and lysolipids with mitochondrial membranes.
      The hypothesis is discussed in relation to current models for the integrated
      action of pro-apoptotic proteins of the Bcl-2 family.

PMID- 11997143
TI  - Characterization of the neuronal changes in the medial prefrontal cortex during
      jaw movement and eyeblink Pavlovian conditioning in the rabbit.
AB  - Medial prefrontal (mPFC) single-unit activity was assessed in defensive
      (eyeblink, EB) and appetitive (jaw movement, JM) Pavlovian conditioning in the
      rabbit. Concomitant heart rate (HR) changes were also assessed. In a first
      experiment robust JM conditioned responses (CRs) were observed to a tone-water
      (CS+) contingency but not to tone-alone (CS-), indicating discriminative JM
      conditioning. However, the CS-evoked accelerative HR response was not
      discriminative. Nevertheless, several single-unit discharge patterns were evoked
      by both tone-water and tone-alone, many of which were uniquely associated with
      either the CS+ or CS-. In a second experiment, Three separate stimuli, consisting
      of tone followed by periorbital shock (tone-shock), water (tone-water), and white
      noise not followed by shock or water, were presented in the same paradigm.
      Discrimination of conditioned JM, EB and HR changes were observed, i.e. each of
      these behavioral responses were uniquely associated with the relevant CS
      presentation. Conditioned bradycardia was evoked by tone-water during the first
      training session, which changed to tachycardia with further training. However,
      conditioned bradycardia was evoked by tone-shock throughout training. Different
      subpopulations of mPFC cells were activated by the tone-shock and tone-water
      contingencies, but a small group of cells were activated by both.

PMID- 11997144
TI  - Behavioral profile of rats submitted to session 1-session 2 in the elevated plus
      maze during diurnal/nocturnal phases and under different illumination conditions.
AB  - The elevated plus-maze (EPM) model usually employs nocturnal species (e.g. rats
      and mice) and the tests are almost exclusively performed during the diurnal phase
      (lights on), leading some laboratories to perform experiments with animals under
      a reversed light cycle to overcome this problem. However, it is questionable
      whether the artificial reversal of the light cycle for short periods guarantees
      modifications in all the physiological parameters found in normal subjects. The
      present study evaluated the session 1-session 2 (S1-S2) EPM profile in rats
      during their normal diurnal or nocturnal phase using different illumination
      conditions. Prior exposure to the EPM decreased open arm exploration for all
      groups in S2, regardless of the circadian phase and illumination condition;
      however, this behavior was decreased in subjects tested during the nocturnal
      phase, when compared to the diurnal phase. Risk assessment (RA) behavior was
      decreased under high illumination for both circadian phases in S1 and increased
      in the first minute of S2, when compared to the last minute of S1. Although open
      arm exploration and RA behavior were decreased under high illumination, when
      compared to low illumination conditions in both circadian phases, general
      locomotor activity was only decreased during the nocturnal phase. The results are
      discussed in terms of circadian variations in the behavioral profile and as a
      possible source of variability in pre-clinical models of anxiety.

PMID- 11997146
TI  - Motivational effects mu- and kappa-opioid agonists following acute and chronic
      restraint stress: involvement of dopamine D(1) and D(2) receptors.
AB  - The influence of both acute and chronic restraint stress on the rewarding
      properties of morphine (1, 2 or 3 mg/kg i.p.) and the aversive effects of
      naloxone (0.5 mg/kg i.p. x3 or 1.0 mg/kg i.p.) or bremazocine (0.4 mg/kg i.p.)
      was investigated. An acute (2 h) but not chronic restraint (2 h daily for 7 days)
      enhanced the morphine place preference, and elicited a place aversion with a
      subthreshold dose of bremazocine. This enhancing effect on the reinforcing
      properties induced by the drugs was prevented by either R(+)-SCH-23390
      hydrochloride (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H3
      benzazepine, 30 microg/kg i.p.) or (+/-)-sulpiride (60 mg/kg i.p.), 10-20 min
      prior to the stress session. Naltrexone pretreatment (1 mg/kg i.p.) abolished the
      stress effect on morphine place preference but not that on bremazocine aversion.
      Instead, nor-BNI (30 microg/3 microl i.c.v.) abolished the stress's effects on
      bremazocine aversion, but did not modify those on morphine preference. These
      results show that: (1) acute stress enhanced the morphine and bremazocine
      conditioned reinforcing effects meanwhile chronic stress did not modify them; (2)
      the stimulation of D(1) and D(2) dopamine receptors is necessary for the
      development of restraint stress-induced sensitization to the conditioned
      reinforcing effects of drugs; and (3) the stimulation mu/delta- and kappa-opioid
      receptors seems to be differentially involved.

PMID- 11997145
TI  - Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities
      are background-dependent.
AB  - A new spontaneous mouse mutation named fierce (frc) is deleted for the nuclear
      receptor Nr2e1 gene (also known as Tlx, mouse homolog of Drosophila tailless).
      The fierce mutation is genetically and phenotypically similar to Nr2e1 targeted
      mutations previously studied on segregating genetic backgrounds. However, we have
      characterized the fierce brain, eye, and behavioural phenotypes on three defined
      genetic backgrounds (C57BL/6J, 129P3/JEms, and B6129F1). The data revealed many
      novel and background-dependent phenotypic characteristics. Whereas abnormalities
      in brain development, hypoplasia of cerebrum and olfactory lobes, were consistent
      on all three backgrounds, our novel finding of enlarged ventricles in 100% and
      overt hydrocephalus in up to 30% of fierce mice were unique to the C57BL/6J
      background. Developmental eye abnormalities were also background-dependent with
      B6129F1-frc mice having less severe thinning of optic layers and less affected
      electroretinogram responses. Impaired regression of hyaloid vessels was observed
      in all backgrounds. Furthermore, retinal vessels were deficient in size and
      number in 129P3/JEms-frc and B6129F1-frc mice but almost entirely absent in
      C57BL/6J-frc mice. We present the first standardized behavioural tests conducted
      on Nr2e1 mutant mice and show that C57BL/6J-frc and B6129F1-frc mice have
      deficits in sensorimotor assays and are hyperaggressive in both sexes and
      backgrounds. However, C57BL/6J-frc mice were significantly more aggressive than
      B6129F1-frc mice. Overall, this extensive characterization of the fierce mutation
      is essential to its application for the study of behavioural, and brain and eye
      developmental disorders. In addition, the background-dependent differences
      revealed will enable the identification of important genetic modifiers.

PMID- 11997147
TI  - Concomitant development of oral dyskinesia and memory deficits in reserpine
      treated male and female mice.
AB  - It has been suggested that reserpine-induced oral dyskinesia in rats may provide
      a new animal model of tardive dyskinesia. Both cognitive deficits and gender have
      been associated with the development of tardive dyskinesia. The aim of the
      present study was to investigate the effects of reserpine administration on the
      development of orofacial dyskinesia and on plus-maze discriminative avoidance
      task (DAT-an animal model of associative learning) in male and female mice. Male
      and female mice received 1.0 mg/kg reserpine or saline subcutaneously on day 1.
      On days 3, 6 and 8, the frequency of vacuous chewing movements (VCM) was
      quantified. On day 6, the DAT conditioning was performed, in a modified elevated
      plus-maze. In one of the enclosed arms, the animals received aversive stimulation
      (light and noise). On day 8, a test session was performed and the time spent by
      the animals in each of the enclosed arms was recorded. Our results showed that
      reserpine-treated male and female mice presented significantly higher VCM when
      compared with respective control groups in all observation days. On day 6,
      reserpine-treated female mice presented significantly higher VCM when compared
      with male mice injected with this drug. The DAT test performed on day 8 showed
      that the time spent in the aversive arm by saline-treated mice was significantly
      lower than the time spent in the non-aversive arm. This difference was not
      observed for reserpine-treated mice. Our results demonstrate the development of
      reserpine-induced oral dyskinesia in both male and female mice. While this oral
      dyskinesia is accompanied by a cognitive deficit in both genders, female mice
      tended to have more severe oral dyskinesia. It is suggested that reserpine
      induced oral dyskinesia may provide a quick, simple and efficient mouse model of
      tardive dyskinesia.

PMID- 11997148
TI  - Post-sensitisation conditioned hyperlocomotion induced by cocaine is augmented as
      a function of dose in C57BL/6J mice.
AB  - The study tested the possibility of a positive relationship between the dose of
      cocaine and the size of the placebo effect generated after contextual
      sensitisation to the behavioural effects of cocaine. Male C57BL/6J mice were
      first injected (subcutaneous, s.c.) over seven successive daily sessions with
      saline or one of three doses of cocaine (2.5, 5 or 7.5 mg/kg), either in the test
      room or in the colony room (before being placed in a novel cage tub). On the test
      day, 24 h after chronic pre-treatment, mice from the four conditions were
      challenged under saline in the test room. Mice were video-recorded and their
      behaviours were scored using a time-sampling technique. A dose-dependent
      development of sensitisation was first generated. On the saline challenge test
      day, significant levels of placebo hyperlocomotion were obtained for mice
      previously given 5 and 7.5 mg/kg, but not 2.5 mg/kg cocaine, the effect being
      significantly greater in the mice pretreated with the highest dose than in those
      receiving the intermediate one, which exhibited a placebo effect that was greater
      than that of the mice pretreated with 2.5 mg/kg cocaine. Therefore, the magnitude
      of the placebo effect was a function of the intensity of the unconditioned
      stimulus (the dose used to generate sensitisation). Such results directly support
      the Pavlovian conditioning account of post-sensitisation placebo effects.

PMID- 11997149
TI  - Contrasting effects of dopamine antagonists and frequency reduction on Fos
      expression induced by lateral hypothalamic stimulation.
AB  - To help further identify the reward-relevant regions activated by electrical
      stimulation of the lateral hypothalamus, Fos expression was quantified in 23
      brain regions in naive, awake rats following non-contingent stimulation with a
      frequency that supports self-stimulation (100 Hz), a frequency that supports only
      minimal responding (50 Hz) and a frequency that does not support self-stimulation
      (25 Hz). Fos expression was also examined in stimulated and unstimulated rats
      pretreated with SCH 23390 (a dopamine D1 antagonist) or spiperone (a D2-like
      antagonist), at doses known to greatly inhibit responding for self-stimulation.
      Lowering the stimulation frequency from 100 to 50 Hz reduced Fos labelling in all
      areas, except for a few cells immediately surrounding the electrode tip. No
      differences were observed between unstimulated rats and those receiving 25 Hz
      stimulation. This suggests that a critical threshold of stimulation is required
      before other reward-relevant regions in the midbrain and forebrain are recruited
      with higher frequency stimulation. Pretreatment with SCH 23390 (0.1 mg/kg)
      inhibited stimulation-induced Fos expression in some key dopamine terminal areas,
      such as the nucleus accumbens (core and shell) and medial caudate-putamen, but
      not in directly driven neurons near the stimulation site. In contrast, spiperone
      (0.1 mg/kg) did not affect the pattern of stimulation-induced Fos expression, but
      induced immunolabelling in the dorsolateral caudate-putamen, an area associated
      with the extrapyramidal side-effects of antipsychotic drugs. These results reveal
      the utility of Fos immunohistochemistry to show how different treatments that
      alter the rewarding impact of electrical brain stimulation achieve their effects
      at the neural level.

PMID- 11997150
TI  - Hippocampal cytotoxic lesion effects on species-typical behaviours in mice.
AB  - The behavioural effects of hippocampal lesions have been extensively documented
      in rats. However, paradigms developed for rats cannot be assumed to transfer
      straightforwardly to mice; the behaviour of the two species differs in many
      respects. Mice are currently the species of choice for targeted genetic
      manipulations. A number of these programs aim to modulate hippocampal function.
      The present studies were therefore designed to provide a behavioural profile of
      selective, cytotoxic hippocampal lesions in tasks appropriate for mice. The
      lesions abolished food hoarding from a source outside the home base, and reduced
      the tendency to displace food pellets from a tube inside the home cage
      (burrowing). Lesioned mice showed reductions of directed exploration (rearing and
      head dipping), but not locomotor activity, in a holeboard and open field, and
      explored the edges of their home cages less when the lids were removed. Nest
      construction was also impaired. These effects were not due to gross motor
      impairments, as formal tests revealed no deficiencies in co-ordination or
      strength. There were suggestions of changes in emotionality, although a more
      consistent finding was that lesioned mice were often slower to initiate behaviour
      in novel surroundings, which may be congruent with the other deficits we
      observed. These results may aid interpretation of the many genetic manipulations
      that target the hippocampus, and of neurodegenerative conditions that induce
      hippocampal pathology.

PMID- 11997151
TI  - Dissociation in retrograde memory for object discriminations and object
      recognition in rats with perirhinal cortex damage.
AB  - This experiment examined the effects of perirhinal cortex (PeRh) lesions on rats'
      retrograde memory for object-discriminations and retrograde object recognition.
      Rats learned one discrimination problem or five concurrent discrimination
      problems 4 weeks before surgery, and a new problem or five new problems during
      the week preceding surgery. Each rat was also familiarized with a sample object
      in an open field, 5, 3, or 1 week before surgery. PeRh-lesioned rats displayed
      normal retention of the object discrimination problems, but on a test of novelty
      preference they showed evidence of impaired recognition of the sample objects. A
      similar dissociation was observed on anterograde tests of object-discrimination
      learning and object recognition. The findings suggest the perirhinal cortex plays
      an essential role in rats' ability to discriminate the familiarity of objects
      previously encountered either before or after surgery, but this ability may not
      be essential for accurate performance of a simple object-discrimination task.

PMID- 11997152
TI  - The inhibitory effect of topical N-acetylcysteine application on myringosclerosis
      in perforated rat tympanic membrane.
AB  - OBJECTIVE: Myringosclerosis often occurs in patients in whom ventilation tube
      insertion and tympanoplasty procedures are performed. Recent studies have
      revealed a relationship between the development of myringosclerosis and oxygen
      derived free radicals, and some investigations have demonstrated that free
      radical scavengers prevent the development of myringosclerosis. N-acetylcysteine
      is a well-known anti-oxidant and anti-inflammatory agent. In this study, we aimed
      to investigate the preventive effect of N-acetylcysteine on myringosclerosis in
      myringotomized rat tympanic membranes. METHODS: Twenty Sprague-Dawley rats were
      bilaterally myringotomized and divided into four groups. Group 1 received no
      treatment, group 2 was treated with topical saline solution in Spongostan, group
      3 received topical 0.6 mg N-acetylcysteine in Spongostan and group 4 received 1.2
      mg N-acetylcysteine in Spongostan daily for 12 days. Tympanic membranes were
      examined by otomicroscopy on day 12. Then, the membranes were harvested and
      evaluated histologically by light microscopy. RESULTS: The tympanic membranes of
      groups 1 and 2 (saline and non-treated) showed extensive occurrence of
      myringosclerosis, whereas groups 3 and 4 (treated with N-acetylcysteine) showed
      lesser occurrence of myringosclerosis in otomicroscopic evaluation (P<0.01).
      Under light microscopic examination, lamina propria of pars tensa was found
      thicker in groups 3 and 4 when compared with groups 1 and 2. There was no
      significant difference between groups 3 and 4 (P: 0.30). CONCLUSIONS: Topically
      applied N-acetylcysteine was found to be effective in the prevention of sclerotic
      lesions in myringotomized rat tympanic membranes.

PMID- 11997153
TI  - Mastoid subperiosteal abscess management in children.
AB  - The management of a mastoid subperiosteal abscess has traditionally required
      mastoidectomy. With the improvement of antibiotic therapy current literature
      supports the treatment of uncomplicated acute mastoiditis with myringotomy and
      intravenous antibiotics. Treatment of a mastoid subperiosteal abscess with
      tympanostomy tube insertion, intravenous antibiotics, and postauricular incision
      and drainage of the abscess avoids the morbidity and potential complications of
      mastoid surgery in young children. Three patients diagnosed with a mastoid
      subperiosteal abscess were managed in this way. The outcome of their treatment
      has been documented with lengthy otologic follow-up. Complete resolution of the
      acute infectious process was achieved in all cases with no evidence of recurrent
      disease.

PMID- 11997154
TI  - Effect of intranasal histamine challenge on Eustachian tube function.
AB  - OBJECTIVE: To show a relationship between intranasal histamine challenge, the
      development of middle ear effusion and Eustachian tube (ET) dysfunction in a rat
      model. METHODS: Non-allergic Sprague-Dawley rats weighing between 450-600 g were
      randomly assigned to receive an intranasal infusion of 16 microl of 10% histamine
      or normal saline. ET function was assessed by using the forced-response test to
      measure passive and active opening and closing pressures at time intervals of 6,
      10, 14, 18, 22, and 26 min and 24 h post-infusion. Mucociliary clearance times
      (MCCTs) of the tubotympanum at 18 min post-infusion were measured by timing the
      transit of dye from the middle ear to the nasopharynx. Outcome measures were ET
      dysfunction and evidence of clinical effusion. RESULTS: Intranasal histamine
      caused acute ET dysfunction when introduced into the nasopharynx demonstrated by
      significant elevations in passive and active opening and closing pressures (P <
      or = 0.001) compared to controls. The largest difference was seen at 26 min post
      infusion. Furthermore, MCCTs were 2.4 times longer after infusing intranasal
      histamine than after saline infusion. No clinically significant effusions were
      evident in either group at any time interval. CONCLUSION: These data demonstrate
      a successful development of an intranasal histamine rat model, in addition to a
      relationship between intranasal histamine challenge and development of acute ET
      dysfunction.

PMID- 11997155
TI  - Decreased serum and pharyngeal antibody levels specific to streptococcal
      lipoteichoic acid in children with recurrent tonsillitis.
AB  - OBJECTIVE: Streptococcus (S.) pyogenes is a common cause of primary as well as
      recurrent tonsillitis (RT). Lipoteichoic acid (LTA) has been proposed as a
      possible candidate for vaccine formulation against streptococcal infections,
      because LTA is a common constituent of streptococci and the antibody to LTA
      inhibits bacterial attachment to epithelial cells in vitro. Streptolysin-O and
      streptococcal whole cell body are highly immunogenic and the antibodies to these
      antigens are reported to be better parameters for streptococcal infections The
      objective of the present study is to investigate how systemic and local immune
      activities against S. pyogenes may be associated with RT. METHODS: Sera from 178
      children with or without RT aged 1-15 years with a median age of 5 years were
      investigated for the levels of total immunoglobulins and antibodies specific to
      streptococcal antigens such as whole cell body, LTA, and streptolysin-O.
      Pharyngeal secretions from 67 children with or without RT aged 2-14 years with a
      median age of 6 years were subjects to secretory IgA (SIgA) antibody levels to
      streptococcal LTA. The antibodies to whole cell body and LTA were measured by
      enzyme-linked immunosorbent assay. Total immunoglobins and the anti-streptolysin
      O antibody were assayed by nephelometry. RESULTS: An age-matched comparison
      revealed that either levels of serum IgG antibody or pharyngeal SIgA antibody to
      streptococcal LTA at 2-5 years of age were significantly lower in RT children
      than in non-RT children (1.39 vs. 5.14 microg/ml, P=0.001; 10.6 vs. 29.9
      units/ng/ml total SIgA, P=0.015; respectively) and correlated inversely to
      episodes of tonsillitis (r=-0.242, P=0.024; r=-0.3, P=0.024; respectively).
      Either serum total immunoglobulin levels of IgG or IgA correlated positively to
      episodes of tonsillitis in children aged 2-5 years (r=0.293, P=0.011; r=0.361,
      P=0.002; respectively). No difference was found on either serum levels of IgG
      antibody to streptococcal whole cell body or antibody to streptolysin-O between
      RT and non-RT children in any age-matched comparisons. High serum antibody levels
      to whole cell body was associated with high antibody levels to streptococcal LTA
      in non-RT children (r=0.198, P<0.05), but no association was found between these
      antibody levels in RT children. CONCLUSIONS: Selective immunologic failure in
      systemic and pharyngeal antibody response to streptococcal LTA may be a potential
      cause of RT in young children.

PMID- 11997156
TI  - A universal newborn hearing screening program in Taiwan.
AB  - OBJECTIVE: Mackay Memorial Hospital and the Children's Hearing Foundation
      established a pilot universal newborn hearing screening program in November 1998.
      Our objective was to assess the feasibility, accuracy and cost effectiveness of
      implementing universal newborn hearing screening in Taiwan. METHOD: Between
      November 1998 and October 2000 a total of 6765 newborns were screened for hearing
      loss prior to discharge from the wellborn nursery at Mackay Memorial Hospital.
      The average age of the subjects at the initial screening test was 52 h. The
      program employed a three stage hearing screening protocol using transient evoked
      otoacoustic emmisions (TEOAE) screening with referral for diagnostic auditory
      brainstem response assessment. RESULTS: The mean TEOAE screening time per ear was
      41.43 s. The overall pass rate at the time of hospital discharge was 93.6%. Thus
      achieving an acceptable referral rate of 6.4% for diagnostic audiological
      assessments. Nine newborns were identified with permanent bilateral hearing
      impairment. 26 newborns were identified with permanent unilateral hearing
      impairment. Infants identified with bilateral hearing loss were immediately
      referred to the Children's Hearing Foundation for hearing aid assessment and
      fitting. Infants as young as 5 weeks of age were successfully fitted with hearing
      instruments and enrolled in the family centered early intervention program at the
      Children's Hearing Foundation. CONCLUSION: The frequency of bilateral congenital
      hearing loss requiring amplification in this population is shown to be
      approximately 1 in 752 newborns. This finding is consistent with previous
      research, which has indicated hearing loss to be the most frequently occurring
      birth defect. Universal newborn hearing screening using TEOAEs proved to be a
      cost effective and feasible method of identifying congenital hearing loss in
      Taiwan. The existence of many successful screening programs worldwide and the
      availability of fast, objective, reliable and inexpensive hearing screening
      procedures means that universal newborn hearing screening is becoming the
      standard of care.

PMID- 11997157
TI  - beta-Lactamase-producing Moraxella catarrhalis may prevent the emergence of
      penicillin-resistant Streptococcus pneumoniae in children with recurrent acute
      otitis media.
AB  - We studied the effect of concomitant nasopharyngeal carriage of beta-lactamase
      producing Moraxella catarrhalis and Haemophilus influenzae on the occurrence of
      penicillin resistance of Streptococcus pneumoniae. We took nasopharyngeal samples
      from 306 children with recurrent otitis media and a history of several antibiotic
      treatments. We could isolate at least one of the pathogens in 89 subjects. Of
      these children 13% carried more than one pathogen. Of the isolated M. catarrhalis
      and H. influenzae strains 93% and 43% produced beta-lactamase, respectively. Of
      the S. pneumoniae strains 25% were non-susceptible (I/R) to penicillin. However,
      in patients carrying beta-lactamase-producing M. catarrhalis together with
      pneumococci all strains were susceptible to penicillin (P=0.0353). This finding
      suggests that beta-lactamase producing M. catarrhalis may hinder the emergence of
      penicillin resistance of S. pneumoniae in children with recurrent acute otitis
      media.

PMID- 11997158
TI  - Effects of electrohydraulic extracorporeal shock wave lithotripsy on
      submandibular gland in the rat: electron microscopic evaluation.
AB  - OBJECTIVES: Extracorporeal shockwave lithotripsy (ESWL) has been applied in
      sialolithiasis as a new treatment modality. The aim of this experimental study is
      to investigate the local effects of electrohydraulic ESWL applied to the right
      submandibular gland of the rats. METHODS: This prospective study was conveyed in
      four groups; groups I, II, III and IV; each group consisting of 20, 20, 18 and 9
      rats, respectively, with a randomized distribution. Groups I, II, III and IV
      received 250, 500, 1000 and 2000 shock waves at 14-16 kV (average 15.1 kV),
      respectively, to the right submandibular glands on the 0th day. In groups I, II,
      III, right submandibular glands of the rats were removed on the 0th, 1st, 7th and
      15th days; in group IV, this procedure could be managed only on the 0th and 7th
      days. Light and electron microscopic evaluation were assessed. Using the light
      microscopic changes, severity of damage score of the glands (SDS) was found.
      Statistical analysis was done using SDSs. RESULTS: Light and electron microscopic
      observations have shown that the damage produced by the shock waves were confined
      to focal areas in the acinar cells (AC), granulated convoluted tubule (GCT) cells
      and blood vessels at all doses applied. Vacuolization in the cytoplasms of the AC
      and GCT cells, disintegration of membranes, alteration in the cytoplasmic
      organization, swelling of the mitochondria and loss of the features were observed
      on electron microscopy. Increase in the secretion rate; stasis and dilatation in
      the blood vessels; blebbing and loss of features in the cytoplasm of the
      endothelial cells were observed. According to the result of the statistical
      analysis using SDSs; at 250 shock wave dose, a statistically significant
      difference between the SDSs of the days (0th, 1st, 7th and 15th) was found
      (P<0.05). The SDS on the 0th day was found to have the lowest value among the
      other days. And also a statistically significant difference was found on the 0th
      day between the SDSs at doses of 250, 500, 1000 and 2000 shock waves (P<0.05).
      The SDS at 250 and 500 shock waves was found to have the lower value than the SDS
      at the 2000 shock wave. It was observed that produced damage was less prominent
      by small doses (250, 500 doses) initially (0th day). Electrohydraulic ESWL caused
      a "patchy type" generalized pathology on submandibular glands of the rats and
      damaged focal areas were widespread all through the gland from the 1st day on.
      CONCLUSION: Formation of the damage was concluded to be related to the direct
      effect of the shock waves rather than the dose used. Electrohydraulic
      lithotripters are not suitable for sialolithiasis because of the focus problems,
      local tissue damage and the risk of the damage to the adjacent structures.

PMID- 11997159
TI  - Intranasal immunization with lipoteichoic acid and cholera toxin evokes specific
      pharyngeal IgA and systemic IgG responses and inhibits streptococcal adherence to
      pharyngeal epithelial cells in mice.
AB  - OBJECTIVE: Streptococcus (S.) pyogenes is common cause of acute tonsillitis.
      Lipoteichoic acid (LTA), which is a common constitute of the cell surface of most
      gram positive bacteria, is known to act as a substance of bacterial site for
      adherence to epithelium and antiserum to LTA is reported to inhibit bacterial
      attachment to epithelial cells in vitro. Cholera toxin subunit B (CT-B) is known
      to be a mucosal adjuvant. The purpose of this study is to investigate whether
      intranasal immunization with LTA and CT-B may be a possible candidate for vaccine
      formulation. METHODS: Six-week-old male BALB/c mice were assigned to three
      experimental groups, mice immunized with LTA and CT-B, with LTA alone and with
      phosphate buffered saline (PBS) as a control. Immunizations were performed
      intranasally every 2 days for 2 weeks in every group. At the 21 days after
      immunization, sera, pharyngeal washings and pharyngeal epithelial cells were
      taken. The levels of serum IgG and pharyngeal IgA antibodies to LTA were measured
      by enzyme-linked immunosorbent assay (ELISA). The adherence rates of S. pyogenes
      pretreated by pharyngeal washings to pharyngeal epithelial cells from the mice
      were determined by in vitro adherence assay. RESULTS: The serum anti-LTA IgG
      antibody levels of either mice immunized with LTA and CT-B or mice immunized with
      LTA alone were significantly higher than those of mice administered with PBS
      alone. The pharyngeal anti-LTA IgA antibody levels of the mice immunized with LTA
      and CT-B were significantly higher than those of either mice with LTA alone or
      mice with PBS alone. The streptococcal adherence rates to pharyngeal epithelial
      cells were significantly decreased by pretreatment with pharyngeal washings from
      the mice immunized with LTA and CT-B as compared with pretreatment with those
      from either mice with PBS or mice with LTA alone. CONCLUSIONS: These data shows
      that intranasal immunization with LTA and CT-B evokes a good pharyngeal IgA
      response as well as systemic IgG response to LTA and inhibits streptococcal
      adherence to pharyngeal epithelial cells, suggesting that intranasal immunization
      with LTA and CT-B may be an effective approach to prevent streptococcal
      tonsillitis.

PMID- 11997160
TI  - Acoustic reflex thresholds at varying click rates in children.
AB  - OBJECTIVE: Previous studies conducted with young adults have shown that
      ipsilateral acoustic reflex thresholds improve with an increase in the click
      rate. Older adults also show an improvement in acoustic reflex thresholds with an
      increase in the click-rate. However, the click-rate induced facilitation (RIF) of
      acoustic reflex thresholds is significantly reduced in older adults. These
      results suggest that slower temporal processing in older adults can be documented
      by measuring the click-RIF of acoustic reflex thresholds. Thus, the click-RIF of
      acoustic reflex thresholds may prove to be a valuable tool for the assessment of
      temporal processing disorders in young children. However, click-RIF of
      ipsilateral acoustic reflex thresholds has not been studied in young normal
      children. The purpose of this study was to evaluate and document the click-RIF in
      young normal children to provide normative data for this age-group. METHODS: The
      study included a total of 30 participants (12 male and 18 female) with normal
      hearing between the ages of 6 and 10 years. Children with outer, middle ear, or
      neurological disorders were excluded from the study. Ipsilateral acoustic reflex
      thresholds were determined in the left and right ears with clicks presented at
      the rate of 50 and 100 per s. The frequency of the probe tone was 226 Hz and
      intensity was 85 dB SPL. A statistical analysis using a three factor mixed MANOVA
      was planned to explore differences between ears, click rates and gender. RESULTS:
      The MANOVA revealed a significant effect (P=0.0000) for the click-rate. There
      were no differences between ears or gender and no interactions. The mean click
      RIF with an increase in the rate from 50 to 100 per s was 10.50 dB. CONCLUSION:
      Comparison of these results with previous results obtained from young adults
      suggests that young normal children show click-RIF that is similar to that
      apparent in young adults.

PMID- 11997161
TI  - Improved detection of polyunsaturated fatty acids as phenacyl esters using liquid
      chromatography-ion trap mass spectrometry.
AB  - The fatty acid composition of Shewanella pealeana was determined by the analysis
      of fatty acid methyl esters via gas chromatography-mass spectrometry (GC-MS) and
      fatty acid 2-oxo-phenylethyl esters via high-performance liquid chromatography
      mass spectrometry (LC-MS) combined with ultra violet (UV) detection. There was
      good agreement between the percentage composition of components determined by GC
      MS and LC-UV analyses. However, LC-MS analysis using Atmospheric Pressure
      Chemical Ionization (APCI) demonstrated dramatically enhanced detection of
      unsaturated fatty acid 2-oxo-phenylethyl esters. The degree of enhancement was
      proportional to the degree of unsaturation. Tests with a pure polyunsaturated
      fatty acid (PUFA) standard gave an absolute detection limit in full scan mode of
      200 pg. In samples, the selectivity of MS over UV gave a significantly lower
      detection limit due to lack of chemical interferences. In 'Selected Reaction
      Monitoring' (SRM) mode, the detection limit was 5 pg. This was essentially
      independent of whether the sample is a standard or complex mixture of fatty
      acids. Tandem mass spectrometry was used to support structural information and to
      enhance the ability to target specific fatty acids. Several PUFAs which were not
      evident from GC-MS analysis were detected and identified by APCI LC-MS, including
      some rare or novel PUFAs from S. pealeana and a menhaden oil standard. Detailed
      analysis of bacterial fatty acid composition by either GC-MS or APCI LC-MS is
      highly preferable to analysis systems based solely on retention time
      identification.

PMID- 11997162
TI  - Identification of Enterococcus spp. based on specific hybridisation with 16S rDNA
      probes.
AB  - The conventional methods for routine enterococci species identification are
      usually based on phenotypic characteristics. However, in recent years, some
      studies have defined specific probes based on both 16S and 23S rRNA genes for the
      identification of some Enterococcus spp. A set of probes based on the 16S rRNA
      gene has been developed in order to evaluate the usefulness of a six-step
      biochemical key for species level identification of enterococci. Probe
      specificity has been evaluated with type collection and environmental strains by
      dot blot hybridisation. A high correlation was obtained between biochemical key
      and hybridisation identifications. This set of probes provides a confirmative
      method for phenotypic species identification.

PMID- 11997163
TI  - Enumeration of viable anaerobic bacteria by solid phase cytometry under aerobic
      conditions.
AB  - Classical enumeration methods for anaerobes are time-consuming and require
      special conditions. Solid phase cytometry (SPC) is a recent laser scanning
      technique for the quantitative detection of fluorescently labelled bacteria on a
      membrane filter that eliminates the need for a growth phase. Fluorescent
      labelling of cells results from the cleavage by intracellular esterases of a
      fluorescein type ester to yield a free fluorescein derivative, which is retained
      only in cells with an intact cytoplasmic membrane. However, as the standard
      labelling procedure is carried out under the conditions of aerobiosis, labelling
      of anaerobic bacteria does not appear to be obvious. We have labelled eight
      strains of vegetative anaerobic bacteria (i.e. Bacteroides thetaiotaomicron,
      Clostridium bifermentans, C. butyricum, C. perfringens, Fusobacterium nucleatum,
      Porphyromonas canoris, P. gingivalis, Propionibacterium acnes) and two strains of
      spores (C. butyricum, C. perfringens,) within 4 h under aerobic conditions.
      However, anaerobiosis remained necessary for spores of C. sordellii, C.
      sporogenes, C. tyrobutyricum. For vegetative cells of all strains, plots of SPC
      versus plate counts were linear with slopes exceeding 1.0, indicating that SPC
      consistently yielded higher numbers of bacteria.

PMID- 11997164
TI  - A comparison of five methods for extraction of bacterial DNA from human faecal
      samples.
AB  - The purity of DNA extracted from faecal samples is a key issue in the sensitivity
      and usefulness of biological analyses such as PCR for infectious pathogens and
      non-pathogens. We have compared the relative efficacy of extraction of bacterial
      DNA (both Gram negative and positive origin) from faeces using four commercial
      kits (FastDNA kit, Bio 101; Nucleospin C+T kit, Macherey-Nagal; Quantum Prep
      Aquapure Genomic DNA isolation kit, Bio-Rad; QIAamp DNA stool mini kit, Qiagen)
      and a non-commercial guanidium isothiocyanate/silica matrix method. Human faecal
      samples were spiked with additional known concentrations of Lactobacillus
      acidophilus or Bacteroides uniformis, the DNA was then extracted by each of the
      five methods, and tested in genus-specific PCRs. The Nucleospin method was the
      most sensitive procedure for the extraction of DNA from a pure bacterial culture
      of Gram-positive L. acidophilus (10(4) bacteria/PCR), and QIAamp and the
      guanidium method were most sensitive for cultures of Gram-negative B. uniformis
      (10(3) bacteria/PCR). However, for faecal samples, the QIAamp kit was the most
      effective extraction method and led to the detection of bacterial DNA over the
      greatest range of spike concentrations for both B. uniformis and L. acidophilus
      in primary PCR reactions. A difference in extraction efficacy was observed
      between faecal samples from different individuals. The use of appropriate DNA
      extraction kits or methods is critical for successful and valid PCR studies on
      clinical, experimental or environmental samples and we recommend that DNA
      extraction techniques are carefully selected with particular regard to the
      specimen type.

PMID- 11997165
TI  - Second derivative UV absorbance analysis to monitor nitrate-reduction by bacteria
      in most probable number determinations.
AB  - Heterotrophic and autotrophic nitrate-reducing bacteria (NRB) play important
      roles in many environments. These bacteria are often enumerated by most probable
      number (MPN) methods. Measuring NO(3)(-) depletion in the MPN cultures is the
      definitive way to determine the presence of NRB. Media used for MPN
      determinations of NRB in oil field waters usually contain high Cl(-)
      concentrations, matching those in the water samples. Many methods for measuring
      NO(3)(-) concentrations, such as ion chromatography (IC), cadmium reduction and
      ion electrode methods, are adversely affected by high concentrations of Cl(-) and
      organic compounds. A second derivative UV absorbance method proved to be a fast
      and reliable means for measuring NO(3)(-) depletion in MPN media used for
      enumerating autotrophic and heterotrophic NRB, without interferences from Cl(-)
      or the organic components in the latter medium. The MPN results for heterotrophic
      NRB determined by the second derivative UV absorbance agreed well with those
      determined by the production of nitrous oxide, and were often higher than those
      determined by measuring nitrate depletion by the diphenylamine spot test.

PMID- 11997166
TI  - Enumeration of 16S rDNA of Desulfotomaculum lineage 1 in rice field soil by real
      time PCR with SybrGreen detection.
AB  - Real-time PCR is a new and highly sensitive method for the quantification of
      microbial organisms in environmental samples. This work was conducted to evaluate
      real-time PCR with SybrGreen (SG) detection as quantification method for
      Desulfotomaculum lineage 1 organisms in samples of rice field soil. The method
      was optimized in several parameters like SG concentration. These allowed
      quantitative PCR with different primer combinations yielding PCR products with
      lengths up to 1066 bp and with sensitivities of 10(2) targets for all assays. The
      detection limit in environmental DNA extracts (rice bulk soil and rice roots) was
      10(6) targets per gram dry weight according to the dilution of the DNA extracts
      necessary to overcome PCR inhibition of humic substances. A verification, that
      the fluorescence increase was due to specific PCR products, was done by agarose
      gel electrophoresis since melting curve analysis of the PCR products did not show
      a distinct peak in the first derivative, when the environmental DNA extracts were
      used in PCR. Amplification with a primer combination specific for
      Desulfotomaculum lineage 1 organisms showed an abundance of this group of
      approximately 2% and 0.5% of the eubacterial 16S rDNA targets in rice bulk soil
      and rice root samples, respectively. Approximately half of this number was
      obtained in both habitats with a PCR assay specific for a Desulfotomaculum
      sequence cluster obtained previously from rice field soil.

PMID- 11997167
TI  - Measurement and characterization of cellulase activity in sclerophyllous forest
      litter.
AB  - Cellulases are enzymatic proteins which hydrolyze cellulose polymers to smaller
      oligosaccharides, cellobiose and glucose. They consist in three major types of
      enzymes: endoglucanases (EC 3.2.1.4), cellobiohydrolases (EC 3.2.1.91) and beta
      glucosidases (EC 3.2.1.21) which play an essential role in carbon turnover of
      forest ecosystem. The aim of this study was firstly to determine the parameters
      (i.e. buffer type, pH, temperature, quantity of litter, incubation time and
      reagent type) which affect the measurement of cellulase activity in a
      sclerophyllous forest litter, and secondly to compare two methods for measuring
      cellulase activity: a direct method and an extraction method. In the direct
      method, the litter was directly incubated with a buffered solution containing the
      enzyme substrate, whereas in the extraction method, the cellulases were firstly
      extracted before measuring their activity. The results were compared with other
      studies about soil cellulase activity, and it appeared that several parameters
      (buffer type, pH, temperature and sample quantity) which influence the
      measurement of cellulase activity differ according to whether a soil or a litter
      is considered. Concerning the procedure used for the measurement of cellulase
      activity, results showed that the activity values were higher when using an
      extraction procedure than when using a direct procedure. The extraction
      procedure, combined with a concentration stage of the extract, also allowed
      electrophoretic analysis (PAGE) of the cellulases extracted from the litter. The
      electrophoretic pattern revealed two cellulase isoenzymes which may be related to
      the occurrence of two pH-activity peaks of these enzymes when citrate buffer was
      used for the measurement of cellulase activity in the litter.

PMID- 11997168
TI  - Direct mass spectrometric measurement of gases in soil monoliths.
AB  - An integrated approach to gas analysis in soil cores was conducted to provide a
      novel method for observing the gas dynamics associated with upland soil
      ecosystems. Depth profiles of the O(2), Ar, CO(2), CH(4), N(2) and NO(x)
      concentrations in intact soil monoliths were obtained simultaneously using
      membrane inlet mass spectrometry (MIMS). This technique enables the direct
      measurement of multiple gas species throughout the soil core with minimal
      disturbance. Depth profiles provided data on the vertical heterogeneity of gas
      concentrations, while horizontal heterogeneity was monitored by comparison
      between profiles. Detailed descriptions of the modifications to current MIMS
      methods for in situ environmental monitoring of terrestrial soils are provided.
      These included a thorough examination of calibration of the MIMS probe in gas
      phase, stirred and unstirred H(2)O, or between glass beads immersed in H(2)O.
      Calibration was also carried out in sterile (autoclaved) soil. The mean
      concentrations of CO(2) and CH(4) in the soil monoliths increased from 27 microM
      and undetectable levels respectively at the surface, to maximum values of 3.6 mM
      and 4.3 microM at 12-cm depth. These changes corresponded with decreases in mean
      O(2), Ar and N(2) concentration from 300, 20 and 720 microM respectively to 0-6,
      10 and 574 microM at 12-cm depth. These data indicated the presence of a gradient
      within the core from an aerobic environment to an O(2)-depleted, but not in all
      cases a completely anaerobic, one. This transition corresponded, to some extent,
      with that between the upper and lower soil horizons. The increased methane and
      CO(2) concentrations observed at depth are indicative of anaerobic environments.
      General trends associated with the gradually changing vertical heterogeneity of
      these gas profiles and the transition towards anaerobiosis did not provide
      evidence for the existence of localised microsites. Some evidence for microsite
      specific microbial communities was however, provided by observation of broad
      zones of accumulation of NO(x) species, but only at concentrations close to the
      limit of detection of the method. The ratio of each gas, to argon was calculated
      at each depth. This was done to correct for physical parameters, which influence
      inert and biologically active gases, equally. The amount of di-nitrogen as a
      ratio to Ar was seen to increase with depth. This could be evidence for
      denitrification in the lower horizon. An example of the dynamic 'online' data
      collection capabilities is provided for diurnal oscillations in subsurface (5 cm)
      soil gas concentrations.

PMID- 11997169
TI  - Denaturing gradient gel electrophoresis (DGGE) approaches to study the diversity
      of ammonia-oxidizing bacteria.
AB  - Denaturing gradient gel electrophoresis (DGGE) of PCR amplicons of the ammonia
      monooxygenase gene (amoA) was developed and employed to investigate the diversity
      of ammonia-oxidizing bacteria (AOB) in four different habitats. The results were
      compared to DGGE of PCR-amplified partial 16S rDNA sequences made with primers
      specific for ammonia-oxidizing bacteria. Potential problems, such as primer
      degeneracy and multiple gene copies of the amoA gene, were investigated to
      evaluate and minimize their possible impact on the outcome of a DGGE analysis.
      amoA and 16S rDNA amplicons were cloned, and a number of clones screened by DGGE
      to determine the abundance of different motility types in the clone library. The
      abundance of clones was compared to the relative intensity of bands emerging in
      the band pattern produced by direct amplification of the genes from the
      environmental sample. Selected clones were sequenced to evaluate the specificity
      of the respective primers. The 16S rDNA primer pair, reported to be specific for
      ammonia-oxidizing bacteria (AOB), generated several sequences that were not
      related to the known Nitrosospira-Nitrosomonas group and, thus, not likely to be
      ammonia oxidizers. However, no false positives were found among the sequences
      retrieved with the modified amoA primers. Some phylogenetic information could be
      deduced from the position of amoA bands in DGGE gels. The Nitrosomonas-like
      sequences were found within a denaturant range from 30% to 46%, whereas the
      Nitrosospira-like sequences migrated to 50% to 60% denaturant. The majority of
      retrieved sequences from all four habitats with high ammonia loads were
      Nitrosomonas-like and only few Nitrosospira-like sequences were detected.

PMID- 11997170
TI  - A simple method to isolate salt-tolerant myxobacteria from marine samples.
AB  - This paper describes a simple method for the isolation of salt-tolerant
      myxobacteria from marine conditions. As the results show in this paper, salt
      tolerant myxobacteria are found to be able to grow, but unable to form fruiting
      bodies at high salt concentrations. The fruiting body structures of the salt
      tolerant strains were all formed in conditions with lower seawater content, i.e.
      lower than 60% seawater (about 2.0% salt content) or distilled water supplemented
      with MgCl(2). The method picked up the fruiting bodies for isolation.

PMID- 11997171
TI  - Introducing antisense oligonucleotides into Pneumocystis carinii.
AB  - To improve the knowledge on Pneumocystis carinii growth, a homologous P. carinii
      transformation system would provide a tool to promote replication of this fungus.
      Antisense oligonucleotides have been successfully introduced by electroporation
      or direct uptake in order to downregulate the prohibitin negative function on
      cell cycle.

PMID- 11997172
TI  - Restriction fragment length polymorphism of rRNA operons for discrimination and
      intergenic spacer sequences for cataloging of Bacillus subtilis sub-groups.
AB  - Restriction fragment length polymorphism of rRNA operons (RFLP) and 16S-23S rRNA
      intergenic region (ISR) sequences of Bacillus subtilis subsp. subtilis, B.
      subtilis subsp. spizizenii, and B. atrophaeus were compared. ISR sequences of the
      B. subtilis subspecies were extremely similar (W23 versus 168 rrn H, J, G,W;
      96.8%; rrn D, E; 98.4%; rrnB; 97.9%) and, therefore, not useful for their
      differentiation. However, RFLP of rRNA operons of the B. subtilis subspecies were
      distinct in terms of numbers and organization within the genome (e.g. the 168 sub
      group generally contained 8.3- and 8.0-kb fragments absent in the W23 sub-group).
      The more distantly related B. atrophaeus was distinct from both B. subtilis
      subspecies in terms of ISR sequence and rRNA operon number and organization. RFLP
      of rRNA operons discriminates the two sub-groups of Bacillus subtilis that are
      indistinguishable by ISR sequence. However, ISR sequence defines the relatedness
      of B. subtilis to other species (e.g. B. atrophaeus) within the genus Bacillus.

PMID- 11997173
TI  - Reexamining the polyadenylation signal: were we wrong about AAUAAA?
AB  - Polyadenylation is the process by which most eukaryotic mRNAs form their 3' ends.
      It was long held that polyadenylation required the sequence AAUAAA and that 90%
      of mRNAs had AAUAAA within 30 nucleotides of the site of poly(A) addition. More
      recent studies, aided by computer analysis of sequences made available in GenBank
      and expressed sequence tag (EST) databases, have suggested that the actual
      incidence of AAUAAA is much lower, perhaps as low as 50-60%. Reproductive
      biologists have long recognized that a large number of mRNAs in male germ cells
      of mammals lack AAUAAA but are otherwise normally polyadenylated. Recent research
      in our laboratory has uncovered a new form of an essential polyadenylation
      protein, tauCstF-64, that is most highly expressed in male germ cells, and to a
      smaller extent in the brain, and which we propose plays a significant role in
      AAUAAA-independent mRNA polyadenylation in germ cells.

PMID- 11997174
TI  - Steroidogenic enzyme gene expression in the human brain.
AB  - mRNA, protein and activity for the enzymes required for the synthesis of adrenal
      corticosteroids have been demonstrated in rat brains by several laboratories. In
      this study real-time RT-PCR was used to determine whether mRNA for these enzymes
      are expressed in the human amygdala, caudate nucleus, cerebellum, corpus
      callosum, hippocampus, spinal cord, and thalamus. Published sequences for the
      human adrenal enzymes were used to construct primers. RESULTS: mRNAs encoding
      cholesterol side-chain cleavage enzyme (CYP11A gene), 17beta-hydroxylase (CYP17),
      3beta-hydroxysteroid dehydrogenase (3beta-HSD), 21-hydroxylase (CYP21), 11beta
      hydroxysteroid dehydrogenase (11beta-HSD2) and glucocorticoid and
      mineralocorticoid receptors were detectable in all anatomical regions evaluated.
      The 11beta-hydroxylase mRNA was detected in all except cerebellum and
      hippocampus. The aldosterone synthase mRNA was not found in amygdala, cerebellum
      or hippocampus. Levels of transcripts were 10(-1)-10(-7)-fold lower than those in
      the adrenal, with corpus callosum and spinal cord having the highest
      concentrations. Enzyme activity or relevance is yet unknown.

PMID- 11997175
TI  - Conserved mammalian gonadotropin-releasing hormone receptor carboxyl terminal
      amino acids regulate ligand binding, effector coupling and internalization.
AB  - The mammalian gonadotropin-releasing hormone receptor (GnRHR), with 327 amino
      acids, is among the smallest G protein coupled receptors identified. Absent from
      this receptor is the cytoplasmic tail, characteristic of other members of this
      superfamily, which frequently mediates desensitization and down-regulation. The
      fifteen carboxyl terminal residues in the mammalian GnRHR are absolutely
      conserved, suggesting important roles for these residues. In the current study,
      mutations of the mammalian GnRHR were made to study the carboxyl terminus. The
      receptor mutant GnRHR(Ser(326)Ala) was reduced in ligand affinity (117% reduction
      compared to wild type (wt)), while receptor numbers and internalization remained
      unchanged. GnRHR(Ser(326)Tyr) was decreased in effector coupling, while ligand
      affinity remained unchanged compared to wt. These studies also show that, while
      mutation of Ser(326) caused a change in ligand binding and effector coupling,
      truncation at this residue (GnRHR[des(326-327)]) had no measurable effect on
      GnRHR ligand binding, effector coupling or internalization, functions which
      appear to require different structural determinants than expression and routing.
      Removal of all three carboxyl terminal residues (Phe(325), Ser(326) and Leu(327))
      or mutation of the receptor (GnRHR[Phe(325)Ala]) caused a complete loss of
      measurable ligand binding and effector coupling, clearly suggesting an
      unexplained role for Phe(325).

PMID- 11997176
TI  - Opposing effects of glucocorticoids on beta(3)-adrenergic receptor expression in
      HIB-1B brown adipocytes.
AB  - Glucocorticoids (GC) have been reported to promptly repress beta(3)-adrenergic
      receptor (beta(3)-AR) gene transcription in a white adipose tissue cell line.
      However, the effect of these hormones on beta(3)-AR expression in brown adipose
      tissue in vivo suggests a more complex mechanism of action. To avoid potential in
      vivo confounding variables, we investigated the effect of GC on the beta(3)-AR of
      HIB-1B brown adipocytes. While beta(3)-AR mRNA had same rapid turnover as in
      white fat cells, 1.5-2 h, the time course of its descent following dexamethasone
      was complex. A rapid initial descent beta(3)-AR mRNA with t(1/2) approximately
      1.6 h was consistent with a prompt, complete inhibition of transcription. Such
      rapid initial phase was followed approximately 2 h later by a plateau or even an
      increase of beta(3)-AR mRNA, to descend thereafter following a slower single
      exponential (t(1/2) approximately 10 h). The change in the time course was
      abrogated by cycloheximide, and was not due to dexamethasone degradation or
      stabilization of beta(3)-AR mRNA at later times after dexamethasone. In vivo, a
      sufficiently large dose of dexamethasone was associated with a transient
      approximately 70% reduction of brown adipose tissue beta(3)-AR mRNA by 4 h and
      full recovery by 24 h. These findings suggest that GC have two opposing effects
      on beta(3)-AR gene expression: they rapidly and directly inhibit transcription
      but also induce a rapidly turned-over protein (C/EBPbeta?) that stimulates gene
      transcription. The relative magnitude of these two effects may vary explaining
      apparently discrepant observations.

PMID- 11997177
TI  - Androgen receptor interactions with Oct-1 and Brn-1 are physically and
      functionally distinct.
AB  - POU domain proteins interact positively or negatively with steroid hormone
      receptors, depending on the precise array of these and other factors assembled on
      target gene promoters. Octamer transcription factor 1 (Oct-1), a ubiquitous POU
      factor, is implicated in androgen induction of the mouse sex-limited protein
      (Slp) gene based on protein-DNA interaction studies. However, direct evidence for
      a role of Oct-1 in the hormone response has been difficult to obtain. Brain 1
      (Brn-1), another POU factor, is more tissue-specific, expressing in brain and
      also in kidney, which is a major site of Slp synthesis. We compared the
      interaction of the androgen receptor (AR) with Oct-1 and Brn-1 to reveal the more
      likely candidate for regulation of Slp. In transfection, addition of either Oct-1
      or Brn-1 reduced AR activation, regardless of the presence of an octamer-like
      sequence in the enhancer, suggesting interference was indirect. However, when the
      octamer-like element was changed to a consensus octamer site, Brn-1, but not Oct
      1, strongly enhanced androgen activation. This correlated with Brn-l's preference
      for the consensus octamer sequence in DNA binding assays. Direct interaction of
      AR with glutathione-S-transferase-(GST)-fused Oct-1 was DNA-dependent, while Brn
      l-AR association was not. Chimeric Brn-1 and Oct-1 POU domains demonstrated that
      the DNA-dependent AR interaction relied on the origin of the POU homeodomain.
      However, in the context of full-length Brn-1 and Oct-1 chimeric proteins, the POU
      homedomain was not sufficient to confer the distinct behaviors of these factors
      in vivo, but instead revealed the importance of an N-terminal transactivation
      domain in Brn-1. These results demonstrate that functional interaction of Oct-1
      and Brn-1 with AR is determined by the precise sequence of the octamer binding
      site, and by differential interaction of the POU factors with AR and other
      components of the transcriptional machinery.

PMID- 11997178
TI  - Prolactin is a component of the human synovial liquid and modulates the growth
      and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.
AB  - The hormone prolactin (PRL) is the product of a single gene synthesized by
      pituitary and many extrapituitary tissues. In this study, we have purified and
      sequenced by mass spectrometry a 29 kDa protein from human synovial liquid, bound
      to the proteoglycan component of synovial liquid that showed an identical
      sequence in 20 amino acids to hPRL. We have also found PRL receptor (PRLR) in
      human knee tissues. The cartilage from osteoarthritic patients shows transcripts
      of the long PRLR isoform while synovial tissue expresses the intermediate PRLR
      isoform. Pluripotent mesenchymal stem cells (MSCs) can be isolated from adult
      bone marrow providing an excellent tool to study MSC-derived differentiation
      processes. We analyzed the expression of the PRL-PRLR system in hMSCs and during
      the acquisition of chondrocyte phenotype. We show by RT-PCR that intermediate
      PRLR isoform is expressed in hMSCs and that PRL exerts a significant increase in
      cell proliferation. In MSC aggregates cultured in chemically defined medium, we
      found that extrapituitary PRL transcripts are expressed and the receptor switches
      isoform expression from the intermediate to long isoform. Furthermore, in cell
      aggregates, PRL induces type II collagen and extrapituitary PRL expression.
      Histomorphologic analysis of cell aggregates showed that PRL induces the
      synthesis of proteoglycans and, in combination with glucocorticoids, a tissue
      structure with cells organized in longitudinal columns. Under the above
      conditions, electron microscopic observations show that PRL both downregulates
      the formation of fibrils of type II collagen and induces cell-cell interactions.
      All the results presented are consistent with a role of the PRL-PRLR system in
      bone/cartilage formation/repair processes.

PMID- 11997179
TI  - Growth-stimulatory and transcriptional activation properties of raloxifene in
      human endometrial Ishikawa cells.
AB  - Raloxifene (Ral) has estrogenic activity in bone and cardiovascular tissues, but
      is antiestrogenic in breast and has limited uterotrophic activity in mice. Here
      we report that Ral stimulates the growth of human endometrial Ishikawa tumors
      implanted in the mammary fat pad of nude ovariectomized mice. In cultured
      Ishikawa cells, Ral has agonist effects on transcription mediated by the
      progesterone receptor, an endogenous estrogen target gene, and on expression of
      reporter genes containing estrogen response elements (EREs). Both Ral and
      tamoxifen (Tam), but not estradiol, stimulated transcription mediated by the
      activator protein 1 at micromolar concentrations. However, this effect correlated
      with induction of cellular death at high concentrations of Ral or Tam and was not
      observed at lower concentrations. Our results suggest that Ral has stimulatory
      effects in Ishikawa cells on both cellular growth and gene transcription, and
      that EREs can mediate some of these effects.

PMID- 11997180
TI  - Cytokine-induced apoptosis and necrosis are preceded by disruption of the
      mitochondrial membrane potential (Deltapsi(m)) in pancreatic RINm5F cells:
      prevention by Bcl-2.
AB  - The mechanisms of cytokine-induced beta-cell death are poorly characterised. In
      rat insulin-producing RINm5F cells, the combination of interleukin-1beta,
      interferon-gamma and tumour necrosis factor-alpha presently induced disruption of
      the mitochondrial membrane potential (Deltapsi(m)) as demonstrated by reduced JC
      1 fluorescence. The reduction of Deltapsi(m) was maximal after 8 h and was
      preceded by increased formation of reactive oxygen species (ROS), as assessed by
      dichlorofluorescein-diacetate (DCFH-DA) fluorescence. A nitric oxide synthase-,
      but not a ROS-inhibitor, prevented cytokine-induced loss of Deltapsi(m).
      Overexpression of the anti-apoptotic protein Bcl-2 increased both JC-1 and DCFH
      DA fluorescence, which was paralleled by protection against cytokine-induced
      apoptosis and necrosis. It is concluded that cytokines induce a nitric oxide
      dependent disruption of Deltapsi(m) and that this may be a necessary event for
      both beta-cell apoptosis and necrosis. Bcl-2 may prevent beta-cell death by
      counteracting mitochondrial permeability transition.

PMID- 11997181
TI  - Leptin promotes the tyrosine phosphorylation of SHC proteins and SHC association
      with GRB2.
AB  - The identification and characterization of proteins that become tyrosine
      phosphorylated in response to growth factor stimulation is critical for
      furthering our understanding of the signal transduction pathways involved in the
      regulation of cell proliferation, differentiation as well as metabolic
      activities. In this report, we demonstrate for the first time, that leptin is
      able to induce the tyrosine phosphorylation of the SH(2) containing protein SHC.
      These studies have been carried out on a human embryonic cell line (HEK 293)
      transfected with the cDNA encoding for the long form of the leptin receptor and
      stably expressing the receptor itself. We also shown that upon tyrosine
      phosphorylation, SHC associated with the adaptor protein, Grb(2). The formation
      of this complex may directly link tyrosine phosphorylation events to Ras
      activation and may be a critical step in proliferation and/or differentiation of
      cells. In conclusion, these results indicate that leptin receptor, after binding
      the ligand, activates several pathways for signal transduction that might lead to
      mitogenic effect.

PMID- 11997182
TI  - Effects of pro-inflammatory cytokines and chemokines on leptin production in
      human adipose tissue in vitro.
AB  - Leptin is synthesized in adipocytes and acts primarily through central pathways
      suppressing appetite and increasing the metabolic rate in rodents as well as in
      humans. Recently leptin has also been suggested to have peripheral effects and be
      involved in insulin action. Since cytokines and chemokines may have effects on
      appetite regulation as well as on some of the obesity-related complications e.g.
      insulin resistance and cardiovascular disease, we investigated the effects of
      various cytokines and chemokines on leptin production in human adipose tissue
      fragments in vitro. Abdominal subcutaneous adipose tissue from healthy normal to
      overweight females was incubated for up to 48 h with the cytokines: tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL
      1beta) and the chemokine: interleukin-8 (IL-8). IL-1beta (50 ng/ml) and TNF-alpha
      (10 ng/ml) decreased leptin production by 30-50% (P<0.05) and gene expression by
      80-90% (P<0.05). In contrast, IL-6 and IL-8 had no effect on either leptin
      production or leptin gene expression. Interestingly, IL-1beta elicited a biphasic
      effect on leptin release with an incremental phase observed within 4 h with no
      concomitant change in leptin gene expression, followed by a long-lasting
      inhibition of leptin release and leptin gene expression. This could suggest that
      IL-1beta through a post-translational pathway induced an acute increase in leptin
      secretion, perhaps through the release of leptin from a pre-formed pool within
      the adipose tissue. The long-term decrease in both leptin secretion and
      transcription could indicate that pro-inflammatory cytokines such as IL-1beta and
      TNF-alpha might influence the circulating leptin levels and thereby influence the
      adipose tissue to brain signalling, which could be of importance in relation to
      the obesity-associated diseases such as insulin resistance and cardiovascular
      disease.

PMID- 11997183
TI  - The casein mRNA decay changes in parallel with the poly(A) tail length in the
      mouse mammary gland.
AB  - Using beta- and gamma-casein mRNAs, the relationship between poly(A) tail length
      and half-life of mRNA is determined in the mouse mammary gland during pregnancy
      and lactation. beta- and gamma-Casein mRNAs increase before and after
      parturition, respectively. The poly(A) tail as well as the half-life of casein
      mRNA becomes longer upon the active casein mRNA synthesis. The poly(A) tail is
      shortened gradually as lactation progresses. The half-life of mRNA decreases
      approximately from 20 h at early to 4 h at late lactation. Northern blot analysis
      reveals that nuclear RNA has the same poly(A) tail length as casein mRNA in the
      cytoplasm does. Thus, the mammary gland changes the poly(A) tail length of casein
      mRNA. The poly(A) tail length changes in parallel with the level of poly(A)
      polymerase (PAP) mRNA during pregnancy and lactation, suggesting that the mammary
      gland determines the poly(A) tail length of casein mRNA through the change in the
      PAP gene expression. As the half-life of casein mRNA is related with the degree
      of polyadenylation, we conclude that the poly(A) tail elongation and shortening
      is a mechanism in regulating the mRNA decay.

PMID- 11997184
TI  - Frequent deletion of chromosome 3 in malignant sporadic pancreatic endocrine
      tumors.
AB  - Pancreatic endocrine tumors (PETs) arise from neuroendocrine cells in and around
      the pancreas. As loss of heterozygosity (LOH) of chromosome 3 has been reported
      in sporadic PETs, we examined 16 sporadic PETs for LOH of 10 polymorphic DNA
      markers spanning both arms of chromosome 3. LOH was demonstrated in 4 of 8 (50%)
      sporadic PETs with hepatic metastasis, but in none of 8 sporadic PETs without
      hepatic involvement. The smallest common-deleted region (SCDR) mapped to 3q27
      qter. Analysis of this data with the status of markers on chromosomes 1, 11, and
      MEN1 mutations in these 16 sporadic PETs revealed that chromosome 3q loss may be
      a late event in sporadic PET tumorigenesis. These data, combined with reports
      from other investigators, indicate that chromosome 3q27-qter may contain a tumor
      suppressor gene that's important in the tumorigenesis of sporadic PETs.

PMID- 11997185
TI  - Regulation of PTH-related protein gene expression by vitamin D in PC-3 prostate
      cancer cells.
AB  - Parathyroid hormone-related protein (PTHrP) is expressed by prostate cancer
      cells. Since PTHrP increases prostate cancer cell growth and enhances the
      osteolytic effects of prostate cancer cells, it is important to control PTHrP
      expression in prostate cancer. Vitamin D exerts a protective effect against
      prostate cancer through its antiproliferative actions. We investigated whether
      this steroid also downregulates PTHrP gene transcription, using the human
      prostate cancer cell line PC-3 as a model system. We report that PTHrP mRNA and
      secreted protein levels are downregulated by 1,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)) via a transcriptional mechanism. We also show that PTHrP gene
      expression is upregulated, also via a transcriptional mechanism, by epidermal
      growth factor (EGF), which is normally secreted by prostate cancer cells.
      1,25(OH)(2)D(3) reversed the EGF-induced PTHrP upregulation at both the mRNA and
      protein levels. Since PTHrP enhances prostate cancer cell growth, this study
      demonstrates the importance of maintaining adequate levels of 1,25(OH)(2)D(3).

PMID- 11997186
TI  - Growth hormone regulation of rat liver gene expression assessed by SSH and
      microarray.
AB  - The sexually dimorphic secretion of growth hormone (GH) that prevails in the rat
      leads to a sex-differentiated expression of GH target genes, particularly in the
      liver. We have used subtractive suppressive hybridization (SSH) to search for new
      target genes induced by the female-characteristic, near continuous, pattern of GH
      secretion. Microarrays and dot-blot hybridizations were used in an attempt to
      confirm differential ratios of expression of obtained SSH clones. Out of 173
      unique SSH clones, 41 could be verified as differentially expressed. Among these,
      we identified 17 known genes not previously recognized as differentially
      regulated by the sex-specific GH pattern. Additional SSH clones may also
      represent genes subjected to sex-specific GH regulation since only transcripts
      abundantly expressed could be verified. Optimized analyses, specific for each
      gene, are required to fully characterize the degree of differential expression.

PMID- 11997187
TI  - Amino acid- and lipid-induced insulin resistance in rat heart: molecular
      mechanisms.
AB  - Lipids compete with glucose for utilization by the myocardium. Amino acids are an
      important energetic substrate in the heart but it is unknown whether they reduce
      glucose disposal. The molecular mechanisms by which lipids and amino acids impair
      insulin-mediated glucose disposal in the myocardium are unknown. We evaluated the
      effect of lipids and amino acids on the insulin stimulated glucose uptake in the
      isolated rat heart and explored the involved target proteins. The hearts were
      perfused with 16 mM glucose alone or with 6% lipid or 10% amino acid solutions at
      the rate of 15 ml/min. After 1 h of perfusion (basal period), insulin (240
      nmol/l) was added and maintained for an additional hour. Both lipids and amino
      acids blocked the insulin effect on glucose uptake (P<0.01) and reduced the
      activity of the IRSs/PI 3-kinase/Akt/GSK3 axis leading to the activation of
      glucose transport and glycogen synthesis. Amino acids, but not lipids, increased
      the activity of the p70 S6 kinase leading to the stimulation of protein
      synthesis. Amino acids induce myocardial insulin resistance recruiting the same
      molecular mechanisms as lipids. Amino acids retain an insulin-like stimulatory
      effect on p70 S6 kinase, which is independent from the PI 3-Kinase downstream
      effectors.

PMID- 11997188
TI  - Two isoforms of the early E74 gene, an Ets transcription factor homologue, are
      implicated in the ecdysteroid hierarchy governing vitellogenesis of the mosquito,
      Aedes aegypti.
AB  - In the anautogenous mosquito, Aedes aegypti, vitellogenesis is under the strict
      control of 20-hydroxyecdysone (20E), which is produced via a blood meal-activated
      hormonal cascade. Several genes of the ecdysteroid-regulatory hierarchy are
      conserved between vitellogenesis in mosquitoes and metamorphosis in Drosophila.
      We report characterization of two isoforms of the mosquito early E74 gene
      (AaE74), which have a common C-terminal Ets DNA-binding domain and unique N
      termini. They exhibited a high level of identity to Drosophila E74 isoforms A and
      B and showed structural features typical for Ets transcription factors. Both
      mosquito E74 isoforms bound to an E74 consensus motif C/AGGAA. In the fat body
      and ovary, the transcript of AaE74 isoform homologous to Drosophila E74B was
      induced by a blood meal exhibiting its highest level coinciding with the peak of
      vitellogenesis. In contrast, the transcript of AaE74 isoform homologous to
      Drosophila E74A was activated at the termination of vitellogenesis. These
      findings suggest that AaE74A and AaE74B isoforms play different roles in
      regulation of vitellogenesis in mosquitoes.

PMID- 11997189
TI  - Effect of paternal administration of an antiestrogen, tamoxifen on embryo
      development in rats.
AB  - We have earlier reported that oral administration of tamoxifen causes a dose
      dependent reduction in the fertility of adult male rats. The decrease in
      fertility was mainly due to an increase in pre-implantation loss without an
      effect on fertilizing ability. During the study, an increased incidence of post
      implantation loss of conceptuses sired by tamoxifen-treated male rats was
      observed. A detailed study was undertaken to investigate dose-related changes in
      pre- and post-implantation loss and the stage(s) of development at which these
      losses occurred. The present study demonstrates that tamoxifen treatment produced
      few normal litters as well as significantly increased pre-implantation loss
      without affecting the rate of fertilization. Also a significant increase in the
      number of degenerating embryos at the 2-4-cell stage (days 1-2 of gestation),
      retrieved from the oviduct/uterus of females mated with tamoxifen-treated males
      was observed. Histology of the resorbed fetuses, in both control and treated
      groups, showed presence of trophoblast outgrowth indicative of early placenta
      formation, which normally occurs on days 8-9 of gestation. The present results
      suggest that pre-implantation loss occurred at the 2-4-cell stage and the post
      implantation loss occurred around days 8-9 of gestation, i.e. around
      midgestation. The possible effects of paternal tamoxifen treatment on
      embryogenesis may be due to the reduction of androgens or by the blockage of the
      estrogen receptor by tamoxifen, thereby affecting germ cell maturation during
      spermatogenesis.

PMID- 11997190
TI  - Vitamin A modulates the effects of thyroid hormone on UDP-glucuronosyltransferase
      expression and activity in rat liver.
AB  - We studied the influence of thyroid hormones and vitamin A status on the
      regulation of UDP-glucuronosyltransferase (UGT) expression and the
      glucuronidation of thyroid hormones by UGTs. For this, we used an original model
      of rats fed with different vitamin A diets and implanted subcutaneously by
      osmotic minipumps delivering vehicle or thyroid hormones, which permitted the
      control of plasma thyroid hormone concentrations. The activity and expression of
      family 1 UGTs are correlated and were significantly modified by both thyroid
      status and amounts of retinol in the diet. Dietary vitamin A did not perturbe the
      UGT1A expression in thyroidectomized animals. Thyroid hormones and dietary
      vitamin A did not affect the activity and expression of family 2 UGTs. We
      conclude that thyroid hormones and vitamin A are co-regulator of the UGT1 family
      expression, without affecting the UGT2 family; by modifying activity and
      expression of the bilirubin UOT isoform, a member of UGT1 family, thyroid hormone
      reduced the glucuronidation of T4 and rT3.

PMID- 11997191
TI  - A locust DNA-binding protein involved in gene regulation by juvenile hormone.
AB  - Although juvenile hormone (JH) has essential roles in insect development and
      reproduction, the molecular mechanisms of gene regulation by JH remain an enigma.
      In Locusta migratoria, the partially palindromic 15-nt sequence,
      GAGGTTCGAG(A)/(T)CCT(T)/(C), found upstream of a JH-induced gene, jhp21, was
      designated as a putative juvenile hormone response element (JHRE). When JH
      deprived adult female locusts were treated with the active JH analog, methoprene,
      a fat body nuclear factor that bound specifically to JHRE appeared after 24 h.
      Binding exhibited a preference for an inverted repeat with GAGGTTC in the left
      half-site, a single nucleotide spacer, and a right half-site in which some
      variation is acceptable. Binding to JHRE was abolished by phosphorylation
      catalyzed by a C-type protein kinase present in the nuclear extracts. The DNA
      binding protein is thus believed to be a transcription factor, which is brought
      to an active state through the action of JH and then participates in the
      regulation of certain JH-dependent genes.

PMID- 11997192
TI  - Caring about what dying patients care about caring.

PMID- 11997193
TI  - CT-guided neurolytic splanchnic nerve block by an anterior approach.

PMID- 11997194
TI  - Problems recruiting cancer patients to a comparative clinical trial of drug
      treatments for neuropathic pain in palliative care.

PMID- 11997195
TI  - Inadequate treatment of pain: realities in the everyday world.

PMID- 11997196
TI  - The ethical imperative to relieve pain at life's end.

PMID- 11997197
TI  - Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to
      severe osteoarthritis pain: results from a randomized, placebo-controlled, double
      blind trial and an open-label extension trial.
AB  - A randomized, 4-week, double-blind trial followed by an open-label extension
      trial assessed the efficacy and safety of a once-daily, extended-release morphine
      formulation (Avinza (previously referred to as Morphelan)) in 295 patients with
      chronic, moderate-to-severe osteoarthritis pain who had failed to obtain adequate
      pain relief with NSAIDs and acetaminophen. Participants received one of four
      treatments: Avinza 30 mg once daily (QAM or QPM), MS Contin(R) 15 mg twice daily,
      or placebo twice daily. Patients (n =181) received Avinza QAM or QPM during the
      26-week open-label extension trial and could increase their dose to optimize pain
      control. Avinza and MS Contin reduced pain and improved several sleep measures
      versus placebo. Analgesic efficacy was comparable between Avinza and MS Contin;
      however, Avinza QAM demonstrated greater improvements in overall quality of
      sleep. The most common adverse events were constipation and nausea. The majority
      of AEs occurred at a similar incidence among the active treatment groups.

PMID- 11997198
TI  - Steady-state pharmacokinetic comparison of a new, extended-release, once-daily
      morphine formulation, Avinza, and a twice-daily controlled-release morphine
      formulation in patients with chronic moderate-to-severe pain.
AB  - Extended-release morphine formulations are widely used in the management of
      chronic pain. Avinza (morphine sulfate extended-release [MSER, Morphelan]) is a
      new, once-a-day, extended-release morphine formulation designed to reach target
      concentrations rapidly and maintain concentrations throughout a 24-hour period.
      The primary objective of this study was to compare the 24-hour steady-state
      pharmacokinetic (PK) profiles of morphine and its metabolites (morphine-6
      glucuronide [M6G] and morphine-3-glucuronide [M3G]) following ingestion of MSER
      once-a-day and MS Contin (controlled-release morphine sulfate [CRM]) twice-a-day
      in patients with chronic moderate-to-severe pain. Ten patients with chronic
      moderate-to-severe pain were recruited into an open-label, multiple-dose,
      nonrandomized, two-period, single-center study. All patients were stabilized for
      a minimum of 7 days on a twice-daily dose of CRM associated with an optimal
      balance between pain control and side effects. Patients were then switched to the
      closest equivalent once-daily dose of MSER for a minimum of 10 days. Twenty-four
      hour steady-state PK profiles were obtained on the last day of each treatment
      period and additional clinical and safety assessments were performed. PK data
      were normalized to a 100-mg total daily dose prior to statistical analysis. Nine
      of the 10 patients completed the entire study. MSER and CRM demonstrated similar
      bioavailability (AUC) of morphine and its metabolites. Compared to CRM, MSER
      demonstrated a 19% lower maximum concentration (C(max)), a 66% higher minimum
      concentration (C(min)), and a 44% lower peak-to-trough fluctuation (%FI) over the
      24-hour period. In addition, MSER maintained concentrations above 50% and 75% of
      the C(max) longer than CRM. Clinical efficacy and safety were comparable for MSER
      and CRM. Once-daily MSER approaches maximum morphine concentration more quickly,
      approximates maximum concentration longer, and demonstrates less fluctuation in
      morphine concentration during a 24-hour period than CRM dosed twice daily. The
      pharmacodynamic implications of this profile deserve further study.

PMID- 11997199
TI  - Symptom management in Taiwanese patients with HIV/AIDS.
AB  - The purpose of this study was to explore HIV/AIDS patients' symptom experiences
      and self-care symptom management strategies using a semi-structured
      questionnaire. Concurrently, the investigators gathered information about
      patients' symptom management strategies from healthcare providers. A total of 134
      HIV-infected persons and 31 healthcare providers voluntarily participated in this
      study. Nausea, pain, anxiety, vomiting, diarrhea, fear and lack of appetite were
      described frequently by HIV-infected participants. Nausea, anxiety, diarrhea,
      fever, fear, pain and vomiting were observed frequently by healthcare providers.
      The management strategies used by these patients are presented and the
      differences in findings between Taiwan and Western cultures are discussed. In
      general, the results indicated that healthcare providers hold limited knowledge
      about self-care symptom management of HIV/AIDS. Filling this knowledge gap is an
      essential task for all healthcare providers in Taiwan.

PMID- 11997200
TI  - Death rattle: prevalence, prevention and treatment.
AB  - A retrospective analysis was performed to study the occurrence and treatment of
      death rattle (DR) in 107 consecutive dying patients on the palliative care unit
      of the University Hospital Leuven. The incidence of DR (23%) is lower than
      reported in literature, possibly due to low hydration. We found 2 types of
      rattle: "Real DR" responds generally very well to anticholinergic therapy, and is
      probably caused by non-expectorated secretions. "Pseudo DR" is poorly responsive
      to therapy and is probably caused by bronchial secretions due to pulmonary
      pathology, such as infection, tumor, fluid retention, or aspiration. Rattle
      disappeared in >90% for the patients with real DR. Real DR is a strong predictor
      for death, and 76% (19/25) died within 48h after onset. Administration of
      subcutaneous hyoscine hydrobromide, as a bolus or continuous infusion, is
      effective therapy for real DR and is comfortable for the patient and caregivers.

PMID- 11997201
TI  - How does the general population treat their pain? A survey in Catalonia, Spain.
AB  - Several epidemiological studies have shown that pain is a very common complaint
      in patients who seek medical care. However, the characteristics of how pain is
      treated in the general population have been studied less. The present survey was
      conducted to describe and analyze how the general population of Catalonia (Spain)
      approaches the treatment of their pain complaints. The study was carried out in
      1964 adults who were surveyed by phone about the presence of painful events in
      the last six months, the intensity and location of their pain, what they did to
      treat their pain, and their resulting level of relief. Data were compared by age
      and gender. Pain prevalence was high (78.6%) and more frequent in women. The
      therapeutic strategy most commonly used was a visit to the physician (66.3%),
      followed by self-medication (27.6%) and alternative medicines (20.5%). Drugs were
      the primary treatment used by physicians (86.5%), followed by physical therapy
      (18.1%). Pain in the extremities, back and neck pain were often unsuccessfully
      treated. Self-medication was often performed with acetylsalicylic acid and
      paracetamol (acetaminophen), and was commonly used in conjunction with other
      therapeutic approaches (51.9%). Age (low use of paracetamol in the elderly) and
      gender (low use of paracetamol in men) were related to the type of drug used in
      self-medication. Older men, and those with severe pain located in the chest,
      required hospital admission more commonly. In conclusion, pain is a common reason
      for seeking medical care and using drugs. Therapeutic approaches are often
      related to the type of pain, but also to age or gender. Knowledge of these
      characteristics may allow for a more efficient use of available resources.

PMID- 11997202
TI  - Cancer pain education for patients and the public.
AB  - Pain education for patients and the public is an essential element of improved
      pain management. This article reports on the implementation of a national
      training project, Cancer Pain Education for Patients and the Public (CPEPP). The
      CPEPP curriculum was designed to address the multiple opportunities for pain
      education and to provide resources and support for successful implementation.

PMID- 11997203
TI  - A pilot trial of paroxetine for the treatment of hot flashes and associated
      symptoms in women with breast cancer.
AB  - Abrupt onset of hot flashes poses a significant problem for women treated with
      chemotherapy for breast cancer. Alternatives to hormone replacement, such as the
      use of the selective serotonin re-uptake inhibitor (SSRI) paroxetine
      hydrochloride, are being explored as therapies for hot flashes in this patient
      population. The present study investigated the efficacy of paroxetine for the
      treatment of hot flashes and associated symptoms in women with breast cancer.
      This study included 13 patients who were seen in the Psychosocial Clinic at
      Moffitt Cancer Center. They were referred by their medical oncologist after
      reporting complaints of significant difficulty with hot flashes. Baseline
      questionnaires were completed and a structured diagnostic interview for clinical
      depression was conducted, all of which were repeated 5 weeks after the paroxetine
      20 mg daily was started. Significant improvements were seen in the ratings of hot
      flash severity (P = 0.002). In addition, significant improvements were observed
      in general, emotional, and mental fatigue. Rates of clinically significant
      depressive symptomatology also decreased and sleep quality improved significantly
      as well. Finally, the incidence of clinical depression improved from 39% at
      baseline to 8% after treatment. These preliminary data suggest that the
      antidepressant paroxetine can be helpful in the treatment of hot flashes and
      associated fatigue, sleep disturbance, and depression in women with breast cancer
      treated with chemotherapy. Further controlled studies are needed to more fully
      evaluate the efficacy of the SSRIs for hot flashes in women with breast cancer.

PMID- 11997204
TI  - Olanzapine in the management of cancer pain.
AB  - In cancer patients, cognitive impairment, psychological distress, and anxiety may
      accompany and aggravate pain. Neuroleptics are frequently used to control these
      symptoms and may be used to treat pain that has been unresponsive to more
      conventional approaches. Because of prominent side effects of traditional
      neuroleptics and conflicting data regarding their analgesic efficacy, their use
      in the treatment of pain remains controversial. Olanzapine, an atypical
      neuroleptic, might offer advantages because of its safer side effect profile. It
      has also been shown to have an independent antinociceptive activity in animals.
      The use of olanzapine in the management of cancer pain has not been previously
      described. We prospectively collected the data on 8 cancer patients with severe
      pain, uncontrolled in spite of aggressive opioid titration, who received
      olanzapine to treat severe anxiety and mild cognitive impairment. Patients did
      not meet criteria for delirium and their cognitive impairment was defined as
      cognitive disorder not otherwise specified (NOS) according to DSM-IV. Patients
      received 2.5 to 7.5 mg of olanzapine daily. In all patients, opioid requirements
      had escalated rapidly prior to starting olanzapine. Levels of pain, sedation, and
      opioid use were measured 2 days before and 2 days after olanzapine was started.
      Cognitive state was assessed daily. All 8 patients had marked reduction of the
      daily pain scores. The average daily opioid use decreased significantly in all
      patients. Cognitive impairment and anxiety resolved within 24 hours of initiating
      olanzapine. In these 8 patients, decreased pain scores and opioid requirements
      may have resulted from improvement in cognitive function and the known anxiolytic
      effect of olanzapine. Other mechanisms may include independent or adjuvant
      analgesic effects of olanzapine. We conclude that olanzapine may be useful in the
      treatment of patients with uncontrolled cancer pain associated with cognitive
      impairment or anxiety. Further studies to evaluate possible analgesic effect of
      olanzapine are needed.

PMID- 11997205
TI  - The common properties of neurogenesis in the adult brain: from invertebrates to
      vertebrates.
AB  - Until recently, it was believed that adult brains were unable to generate any new
      neurons. However, it is now commonly known that stem cells remain in the adult
      central nervous system and that adult vertebrates as well as adult invertebrates
      are currently adding new neurons in some specialized structures of their central
      nervous system. In vertebrates, the subventricular zone and the dentate gyrus of
      the hippocampus are the sites of neuronal precursor proliferation. In some
      insects, persistent neurogenesis occurs in the mushroom bodies, which are brain
      structures involved in learning and memory and considered as functional analogues
      of the hippocampus. In both vertebrates and invertebrates, secondary neurogenesis
      (including neuroblast proliferation and neuron differentiation) appears to be
      regulated by hormones, transmitters, growth factors and environmental cues. The
      functional implications of adult neurogenesis have not yet been clearly
      demonstrated and comparative study of the various model systems could contribute
      to better understand this phenomenon. Here, we review and discuss the common
      characteristics of adult neurogenesis in the various animal models studied so
      far.

PMID- 11997206
TI  - Gonadotropin response to GnRH during sexual ontogeny in the common carp, Cyprinus
      carpio.
AB  - This study was designed to reveal whether gonadotropic response to GnRH in the
      common carp (Cyprinus carpio) changes during sexual ontogeny and whether the
      response of FSHbeta and LHbeta subunits is uniform or differential. The study
      comprised fish at the following stages: juveniles (4-month-old females with
      primary oocytes and early spermatogenic males); maturing (9-month-old
      previtellogenic females and advanced spermatogenic males); and mature (16-month
      old postvitellogenic females and spermiating males). Fish were injected with
      superactive salmon GnRH analogue (sGnRHa; 25 microg/kg) and blood was sampled 6,
      12 and 24 h later for cGtH (LH) and sex steroid levels. Pituitaries were taken
      for determination of FSHbeta and LHbeta mRNA levels by slot-blot hybridization
      and for cGTH content in the same glands by radioimmunoassay (RIA). Values were
      compared with the levels prior to sGnRHa administration and with control fish
      sampled at the same intervals. Juvenile fish did not respond at all to sGnRHa. In
      maturing females, FSHbeta mRNA increased by >300%, while that of LHbeta increased
      by 200%. In maturing males, FSHbeta mRNA did not change and only a slight
      increase occurred in that of LHbeta. In 16-month-old postvitellogenic females,
      there was no response of FSHbeta mRNA, while that of LHbeta dramatically
      increased. In spermiating males of the same age, mRNA of both FSHbeta and LHbeta
      increased following sGnRHa injection. Immunoreactive cGtH was present in the
      pituitary and plasma of all fish examined, but in juveniles it did not change
      following sGnRHa injection. In maturing and mature fish of both genders, sGnRHa
      administration was followed by a marked increase in circulating cGtH, concomitant
      with a decrease in its pituitary content, indicating the limited amount of the
      hormone stored in the gland. In conclusion, the response of the gonadotropin
      subunit mRNAs in the common carp was found to be differential and dependent on
      the gender and the phase of sexual ontogeny.

PMID- 11997207
TI  - Presence of angiotensin converting enzyme (ACE) interactive factors in ovaries of
      the grey fleshfly Neobellieria bullata.
AB  - Angiotensin converting enzyme (ACE) activity, defined as a captopril-inhibitable
      dipeptidyl carboxypeptidase activity towards 3H-hippurylglycylglycine, was
      demonstrated in haemolymph, testes and ovaries of the grey fleshfly Neobellieria
      bullata, hereby suggesting a physiological role for ACE in these particular
      tissues. While the ACE activity in haemolymph and testes reached relatively high
      levels, only minute ACE activity could be detected in ovaries throughout the
      entire vitellogenic cycle. Ovarian extracts of Neobellieria bullata do contain,
      however, in addition to Neb-TMOF, the Neobellieria bullata trypsin modulating
      oostatic factor which is an in vitro and a putative in vivo substrate of ACE in
      circulation, several other heat-stable molecules which individually function
      either as an ACE substrate or ACE inhibitor. Presumably these ACE interactive
      factors mask ACE activity in the fly ovaries, as measured by a classic substrate
      binding assay. Purification and characterisation of these ACE
      substrates/inhibitors is in progress and is likely to facilitate the elucidation
      of the enigmatic physiological relevance of ACE in insects.

PMID- 11997208
TI  - Interactions between aromatase (estrogen synthase) and dopamine in the control of
      male sexual behavior in quail.
AB  - In male quail, like in other vertebrates including rodents, testosterone acting
      especially through its estrogenic metabolites is necessary for the activation of
      male sexual behavior. Also, the administration of dopamine agonists and
      antagonists profoundly influences male sexual behavior. How the steroid-sensitive
      neural network and dopamine interact physiologically, remains largely unknown. It
      is often implicitly assumed that testosterone or its metabolite estradiol,
      stimulates male sexual behavior via the modification of dopaminergic
      transmission. We have now identified in quail two possible ways in which dopamine
      could potentially affect sexual behavior by modulating the aromatization of
      testosterone into an estrogen. One is a long-acting mechanism that presumably
      involves the modification of dopaminergic transmission followed by the alteration
      of the genomic expression of aromatase. The other is a more rapid mechanism that
      does not appear to be dopamine receptor-mediated and may involve a direct
      interaction of dopamine with aromatase (possibly via substrate competition). We
      review here the experimental data supporting the existence of these controls of
      aromatase activity by dopamine and discuss the possible contribution of these
      controls to the activation of male sexual behavior.

PMID- 11997209
TI  - Nitric oxide and neuromodulation in the caudal neurosecretory system of teleosts.
AB  - Although evidence exists that nitric oxide (NO) mediates neuroendocrine secretion
      in mammals, the involvement of NO in the neuroendocrine regulation of non
      mammalian vertebrates has yet to be investigated in detail. The present review
      conveys several recent data, suggesting that NO plays a modulatory role in the
      caudal neurosecretory system (CNSS) of teleosts. The presence and distribution of
      neuronal NO synthase (nNOS) was demonstrated in the CNSS of the Nile tilapia
      Oreochromis niloticus by means of NADPHd histochemistry, NOS
      immunohistochemistry, NOS immunogold electron microscopy, the citrulline assay
      for NOS activity and Western blot analysis. NO production by the caudal spinal
      cord homogenates was also evaluated by the oxyhemoglobin assay. On the whole,
      these findings indicate that caudal neurosecretory cells express NOS enzymes and
      presumably produce NO as a cotransmitter. Moreover, the comparison of the nNOS
      distribution with that of urotensins I and II (UI and UII) suggests that
      neurosecretory Dahlgren cells belong to two different functional subpopulations:
      a population of UI/UII secreting nitrergic neurons and a population of non
      nitrergic neurons, which principally secrete UII. These results implicate NO as a
      putative modulator of the release of urotensins from the neurosecretory axon
      terminals. Therefore, like in mammals, NO appears to influence neuroendocrine
      secretion in teleosts.

PMID- 11997210
TI  - Peptide and protein pheromones in amphibians.
AB  - Purification, characterization and biological activity of urodele and anuran sex
      pheromones were reviewed. Female-attracting pheromones obtained from the
      abdominal gland of Cynops pyrrhogaster and C. ensicauda males are peptides
      consisting of 10 amino acid residues being designated sodefrin and silefrin,
      respectively. Each pheromone attracted only conspecific females. Molecular
      cloning of cDNAs encoding sodefrin and silefrin revealed that both are generated
      from precursor proteins. Synthesis of these pheromones is regulated by prolactin
      (PRL) and androgen. Responsiveness of the female vomeronasal epithelium to
      sodefrin is enhanced by PRL and estrogen. The submandibular gland of the male
      terrestrial salamander, Plethodon jardani secretes a 22-kD proteinaceous
      pheromone that enhances female receptivity. It was revealed that every salamander
      synthesizes multiple isoforms of this pheromone, Plethodontid receptivity factor.
      The magnificent tree frog, Litoria splendida breed in an aquatic environment. The
      skin glands of the male secrete a female-attracting peptide pheromone,
      splendipherin, comprising 25 amino acid residues. The significance of the
      structure of the amphibian sex-pheromone as peptide and protein is discussed in
      terms of their species specificity.

PMID- 11997211
TI  - Regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      gene expression by gonadotropin-releasing hormone (GnRH) and sexual steroids in
      the Mediterranean Sea bass.
AB  - The secretion of gonadotropins, the key reproductive hormones in vertebrates, is
      controlled from the brain by the gonadotropin-releasing hormone (GnRH), but also
      by complex steroid feedback mechanisms. In this study, after the recent cloning
      of the three gonadotropin subunits of sea bass (Dicentrarchus labrax), we aimed
      at investigating the effects of GnRH and sexual steroids on pituitary
      gonadotropin mRNA levels, in this valuable aquaculture fish species. Implantation
      of sea bass, in the period of sexual resting, for 12 days with estradiol (E2),
      testosterone (T) or the non-aromatizable androgen dihydrotestosterone (DHT),
      almost suppressed basal expression of FSHbeta (four to 15-fold inhibition from
      control levels), while slightly increasing that of alpha (1.5-fold) and LHbeta
      (approx. twofold) subunits. Further injection with a GnRH analogue (15 microg/kg
      BW; [D-Ala6, Pro9-Net]-mGnRH), had no effect on FSHbeta mRNA levels, but
      stimulated (twofold) pituitary alpha and LHbeta mRNA levels in sham- and T
      implanted fish, and slightly in E2- and DHT-implanted fish (approx. 1.5-fold).
      The GnRHa injection, as expected, elevated plasma LH levels with a parallel
      decrease on LH pituitary content, with no differences between implanted fish. In
      conclusion, high circulating steroid levels seems to exert different action on
      gonadotropin secretion, inhibiting FSH while stimulating LH synthesis. In these
      experimental conditions, the GnRHa stimulate LH synthesis and release, but have
      no effect on FSH synthesis.

PMID- 11997212
TI  - Parathyroid hormone-related protein in lower vertebrates.
AB  - The genes for parathyroid hormone-related protein (PTHrP) have been cloned in two
      teleost fishes, cDNA of sea bream (Sparus aurata) and genomic DNA of puffer fish
      (Fugu rubripes). The gene sequences show that there is significant conservation
      of amino acid identity, with specific domains most highly conserved. The N
      terminus, responsible for bone matrix lysis in mammals and chickens, is present
      in the fish genes with 52% sequence identity to higher vertebrate PTHrP peptides;
      the nuclear transporter region shares 73% identity, and the RNA-binding sequence
      is 65% identical. However, the peptides are shorter then mammalian PTHrP, lacking
      the C-terminus responsible for inhibition of osteoclast lytic activity, but they
      have an additional inserted sequence between amino acids 38 and 54 that is not
      present in higher vertebrate PTHrPs. The N-terminus 1-38 Fugu PTHrP proved to be
      hypercalcaemic in larval Sparus, suggesting that it may be a physiological
      regulator of calcium homeostasis in fish. Using homologous nucleotide probes for
      in situ hybridisation and reverse-transcription polymerase chain reaction (RT
      PCR) of extracted RNA, PTHrP gene expression has been widely found in both
      developing and adult fish. Antiserum to the fish insert sequence demonstrated
      transcription of PTHrP in all stages of Sparus development, and also detected the
      same epitope in tissues of developing frog (Rana temporaria), indicating that
      this has been retained during evolution of the amphibia.

PMID- 11997213
TI  - Regulation of androgen receptor mRNA expression in primary culture of Harderian
      gland cells: cross-talk between steroid hormones.
AB  - The androgen receptor (AR) must be considered a transcription factor belonging to
      the steroid-thyroid hormones receptor superfamily. Previous results gained from
      the Harderian gland, a tubulo-alveolar gland located in the orbital cavity of the
      golden hamster, indicate that Harderian gland cells express mRNAs encoding for
      androgen, glucocorticoid, thyroid hormone (T(3)), and estrogen receptors,
      respectively. Since in other systems, these receptors have been related to the
      expression of the androgen receptor, we have studied the regulation of AR
      expression in primary cultures of the male hamster Harderian gland. Our in vitro
      experiments show that androgen, and thyroid hormones increase the expression of
      AR. Retinoic acids also show a positive effect on AR expression, while exposure
      to glucocorticoid or estrogen blocks AR expression. Since these steroids
      differently modulate AR expression, our results must be considered in the context
      of multi-hormonal control of gene expression that could act through cross-talk
      between members of the steroid-thyroid hormones.

PMID- 11997214
TI  - Peptide differential display: a novel approach for phase transition in locusts.
AB  - Today, the question of the physiological cause of phase transition, the
      transition from the solitary to the gregarious phase, in locusts remains
      unanswered. We hereby present a novel approach by which we have attempted to
      determine whether different phases express or release different peptides in
      similar physiological conditions. For this purpose, a peptidomic analysis of the
      corpora cardiaca and hemolymph of crowded and isolated locusts of Schistocerca
      gregaria was performed using high performance liquid chromatography and matrix
      assisted laser desorption ionisation time of flight mass spectrometry. A
      comparison between the two conditions reveals differences in the number and
      amount of peptides present in the corpora cardiaca and the hemolymph. Further
      research will have to identify these phase specific differences and their role in
      locust phase polymorphism.

PMID- 11997215
TI  - Beetles' choice--proline for energy output: control by AKHs.
AB  - Many beetle species use proline and carbohydrates in a varying ratio to power
      flight. The degree of contribution of either fuel varies widely between species.
      In contrast, dung beetle species investigated, thus far, do not have any
      carbohydrate reserves and rely completely on proline to power energy-costly
      activities such as flight and, probably, walking and ball-rolling. While the
      fruit beetle, Pachnoda sinuata, uses proline and carbohydrates equally during
      flight, proline is solely oxidised during endothermic pre-flight warm-up, as well
      as during flight after prolonged starvation. Thus, proline seems to be the
      essential fuel for activity in beetles, even in flightless ones and in those that
      use proline in combination with carbohydrates; the latter can be completely
      substituted by proline in certain circumstances. It is apparent from the rapid
      decline of energy substrates in flight muscles and haemolymph after the onset of
      flight that mobilisation of stored fuels of the fat body is necessary for
      prolonged flight periods. This task is performed by AKH-type neuropeptides. In
      beetles, like in other insects, these peptides mobilise glycogen via activation
      of glycogen phosphorylase. They also stimulate proline synthesis from alanine and
      acetyl-CoA in the fat body. Acetyl-CoA is derived from the beta-oxidation of
      fatty acids and we propose that the neuropeptides activate triacylglycerol
      lipase.

PMID- 11997216
TI  - The amphibian testis as model to study germ cell progression during
      spermatogenesis.
AB  - Testicular morphology of vertebrate testis indicates requirement of local
      control. In urodeles, the testis is organized in lobes of increasing maturity
      throughout the cephalocaudal axis. The anuran testis is organized in tubules.
      Spermatogenesis occurs in cysts composed by Sertoli cells enveloping germ cells
      at synchronous stages. Moreover, in numerous species germ cell progression lasts
      a year which defines the sexual cycle. Due to the above quoted features, research
      on factors regulating germ cell progression in amphibians may reach greater
      insight as compared with mammalian animal models. In particular, studies on
      endocrine and paracrine/autocrine factors involved in the regulation of germ cell
      functions reveal that fos activation and a J protein, previously specifically
      found in mouse testis, exert an important role in spermatogonial proliferation
      and maturation of post-meiotic stages, respectively.

PMID- 11997217
TI  - Research progress in the stimulatory inputs regulating growth hormone (GH)
      secretion.
AB  - A review is presented on progress in the research of stimulatory inputs that
      regulate growth hormone secretion, including recent results on the action of the
      hypothalamic peptides growth-hormone releasing factor (GHRH) and pituitary
      adenylate cyclase-activating polypeptide (PACAP), as well as that of both
      peptidic (growth hormone-releasing hexapeptide; GHRP-6) and non-peptidyl (L
      163,255) synthetic GHSs on somatotrope cell function.

PMID- 11997218
TI  - Neuropeptides and amphibian prey-catching behavior.
AB  - In mammals, a number of hypothalamic neuropeptides have been implicated in stress
      induced feeding disorders. Recent studies in anurans suggest that stress-related
      neuropeptides may act on elemental aspects of visuomotor control to regulate
      feeding. Corticotropin-releasing hormone (CRH) and alpha-melanocyte-stimulating
      hormone, potent an orexic peptides in mammals, inhibit visually-guided prey
      catching in toads. Neuropeptide Y (NPY), an orexic peptide in mammals, may be an
      important neuromodulator in inhibitory pre-tectal-tectal pathways involved in
      distinguishing predator and prey. Melanocortin, NPY and CRH neurons project onto
      key visuomotor structures within the amphibian brain, suggesting physiological
      roles in the modulation of prey-catching. Thus, neuropeptides involved in feeding
      behavior in mammals influence the efficacy of a visual stimulus in releasing prey
      catching behavior. These neuropeptides may play an important role in how frogs
      and toads gather and process visual information, particularly during stress.

PMID- 11997219
TI  - Calcium homeostasis in crustaceans: subcellular Ca dynamics.
AB  - The molting cycle of crustaceans, associated with renewal and remineralization of
      the cuticle, has emerged as a model system to study regulation of genes that code
      for Ca(2+)-transporting proteins, common to all eukaryotic cells. This article
      reviews state-of-the-art knowledge about how crustacean transporting epithelia
      (gills, hepatopancreas and antennal gland) effect mass transcellular movement of
      Ca(2+) while preventing cytotoxicity. The current model proposed is based on in
      vitro research on the intermolt stage with extrapolation to other molting stages.
      Plasma membrane proteins involved in apical and basolateral Ca(2+) movement (NCX,
      PMCA) are contrasted between aquatic species of different osmotic origin and
      among transporting epithelia of an individual species. Their roles are assessed
      in the context of epithelial Ca(2+) flux derived from organismic approaches.
      Exchange with extracellular environments is integrated with Ca(2+) sequestration
      mechanisms across endomembranes of the ER/SR and mitochondria. Finally, the
      review postulates how new Ca(2+) imaging techniques will allow spatial and
      temporal resolution of Ca(2+) concentration in subcellular domains.

PMID- 11997220
TI  - The role of the anterior neural ridge and Fgf-8 in early forebrain patterning and
      regionalization in Xenopus laevis.
AB  - The tissue, cellular and molecular mechanisms that regulate early regional
      specification of the vertebrate forebrain are largely unknown. We studied the
      expression patterns of Xbf-1, an anterior (and telencephalon) neural-specific
      winged helix transcription factor and Fgf-8, an early-secreted factor. This study
      looked at Xbf-1 and Fgf-8 expression in combination with embryonic grafting
      experiments and also used beads containing the recombinant Fgf-8 protein to
      determine these factors' effects upon forebrain patterning events. We provide
      evidence that additional Fgf-8 displaces Xbf-1 expression posteriorly, suggesting
      a concentration dependence of Fgf-8 for the early distinct regionalization of the
      telencephalic primordia. Also, additional stage 15 mid-anterior neural ridge
      (mANR) transplants inhibited telencephalon development, whereas lateral ANR
      transplants facilitated increased areas of telencephalon development. In both
      cases, these transplantations promoted ectopic expression of Xbf-1. These studies
      suggested that the distinct regionalization of the forebrain primordia involves
      the inhibitory actions of the mANR towards a telencephalon development and
      maintaining bilateral telencephali. These telencephalic primordia are initially
      localized by optimal Fgf-8 expression. The anterior mANR will eventually become
      the anterior and rostral diencephalic tissue. This in vivo study demonstrated Fgf
      8 and the mANR are important in forebrain regionalization.

PMID- 11997221
TI  - Juvenile hormone biosynthesis in the fall armyworm, Spodoptera frugiperda
      (Lepidoptera, Noctuidae).
AB  - The in vitro production of juvenile hormones (JH) was investigated by using
      corpora allata (CA) of larvae and corpora cardiaca-corpora allata (CC-CA)
      complexes of adult females of the fall armyworm Spodoptera frugiperda. In female
      moths, JH release was high compared to that in 5th and 6th instar larvae.
      Concentrations of 0.11-0.12 mM methionine, 180-200 mM Na(+), 5.8-8.3 mM K(+), 10
      50 mM Ca(2+) and a pH range of 5.7-6.3 yielded optimal incorporation of L-[methyl
      (3)H] methionine in vitro by CC-CA complexes. The highest hourly incorporation
      occurred during a 9-h incubation period following a 1.5-h lag-phase. JH release
      from CC-CA complexes of adult females was shown to be age-dependent with a peak
      value on day 2 (approx. 4 pmol h(-1) CA(-1)). By a combination of reversed phase
      (RP)- and normal phase (NP)-high performance liquid chromatography (HPLC), two
      major labelled products released by the complex were separated. One compound co
      migrated with chemically synthesized JH II diol, the second compound with JH III
      diol. Only traces of JH II and III could be detected in some samples. Gland
      extracts also contained both the major radiolabelled products. Double labelling
      experiments using [3H]methionine and [14C]acetate confirmed their de novo
      synthesis in CC-CA complexes of female moths. The nature of chemically
      synthesized reference JH III diol was proved by LC-MS (ESI mass spectrometry) and
      1H-NMR (nuclear magnetic resonance spectroscopy).

PMID- 11997222
TI  - Social modulation of androgen levels in male teleost fish.
AB  - Androgens are classically thought of as the sex steroids controlling male
      reproduction. However, in recent years evidence has accumulated showing that
      androgens can also be affected by the interactions between conspecifics,
      suggesting reciprocal interactions between androgens and behaviour. These results
      have been interpreted as an adaptation for individuals to adjust their agonistic
      motivation and to cope with changes in their social environment. Thus, male-male
      interactions would stimulate the production of androgens, and the levels of
      androgens would be a function of the stability of its social environment
      ['challenge hypothesis', Gen. Comp. Endocrinol. 56 (1984) 417]. Here the
      available data on social modulation of androgen levels in male teleosts are
      reviewed and some predictions of the challenge hypothesis are addressed using
      teleosts as a study model. We investigate the causal link between social status,
      territoriality and elevated androgen levels and the available evidence suggests
      that the social environment indeed modulates the endocrine axis of teleosts. The
      association between higher androgen levels and social rank emerges mainly in
      periods of social instability. As reported in the avian literature, in teleosts
      the trade-off between androgens and parental care is indicated by the fact that
      during the parental phase breeding males decreased their androgen levels. A
      comparison of androgen responsiveness between teleost species with different
      mating and parenting systems also reveals that parenting explains the variation
      observed in androgen responsiveness to a higher degree than the mating strategy.
      Finally, the adaptive value of social modulation of androgens and some of its
      evolutionary consequences are discussed.

PMID- 11997223
TI  - Bioactivity of nacre water-soluble organic matrix from the bivalve mollusk
      Pinctada maxima in three mammalian cell types: fibroblasts, bone marrow stromal
      cells and osteoblasts.
AB  - In vivo and in vitro studies provide strong evidence of the osteogenic activity
      of nacre obtained from Pinctada maxima. The in vitro studies indicate that
      diffusible factors from nacre are involved in cell stimulation. The water-soluble
      matrix (WSM) was extracted from nacre by a non-decalcifying process, and four
      fractions (SE(1)-SE(4)) were separated by SE-HPLC. Those fractions were tested in
      vitro on MRC5 fibroblasts. Alkaline phosphatase (ALP) activity was measured as a
      marker of osteoblastic differentiation. The anti-apoptotic protein Bcl-2 was also
      immunodetected in cultured osteoblasts from rat calvaria. WSM and fraction SE(4)
      increased ALP activity. BMP-2 had the same effect on the cells as WSM and SE(4).
      WSM greatly increased the amount of Bcl-2 in the cytoplasm and nucleus of
      osteoblasts. These in vitro studies support our initial hypothesis that nacre
      organic matrix (WSM) of a bivalve mollusk contains signal-molecules that can
      stimulate the osteogenic pathway in mammalian cells that are targets for bone
      induction.

PMID- 11997224
TI  - Neurohypophysial hormones and renal function in fish and mammals.
AB  - The two major basic neurohypophysial peptides, arginine vasopressin (AVP) of
      mammals and arginine vasotocin (AVT) of all non-mammalian vertebrates, share
      common structure and major roles in regulating renal function. In this review the
      complexity of AVP actions within the mammalian kidney is discussed and
      comparisons are made with the emerging picture of AVT's renal effects in fish. It
      has become apparent that the antidiuretic action of the neurohypophysial hormones
      is an ancient phylogenetic phenomenon, although this is based upon reduced
      glomerular filtration in fish by comparison with predominant tubular effects in
      mammals. Nonetheless, there appears to be retention of AVP effects upon the
      functional heterogeneity of nephron populations in mammals. Preliminary evidence
      for the possible existence of V(2)-type (tubular) neurohypophysial hormone
      receptors in fish, implies possible AVT actions which parallel those in mammals
      on tubular ion transport. Further insight from recent mammalian tubule
      microperfusion studies suggests that in teleost fish both apical (tubular lumen)
      and basolateral (blood borne) AVT have the potential to modulate renal function,
      though this remains to be examined.

PMID- 11997225
TI  - Changes in thyroid hormone levels in chicken liver during fasting and refeeding.
AB  - In chickens, fasting results in increased plasma thyroxine (T(4)) levels and
      decreased plasma 3,5,3'-triiodothyronine (T(3)) levels. Refeeding, in turn,
      restores normal plasma T(3) and T(4) levels. The liver is an important tissue for
      the regulation of circulating thyroid hormone levels. Previous studies
      demonstrated that the increase in hepatic type III deiodinase in fasted chickens
      plays a role in the decrease of plasma T(3). Another factor that could be
      important is the level of T(4) and T(3) uptake by the liver. In mammals, caloric
      restriction is known to diminish transport of T(4) and T(3) into tissues. The
      present study examines whether this is also the case in chicken. Four-week-old
      chickens were subjected to a 24-h starvation period followed by refeeding. Blood
      and liver samples were collected at the start of refeeding and at different times
      of refeeding. Thyroid hormone levels were measured directly in plasma and in
      tissues following extraction. The results demonstrate that intrahepatic T(4)
      levels are increased and T(3) levels are decreased in fasted compared to ad
      libitum fed chickens. The parallel changes in plasma and hepatic T(3) and T(4)
      content demonstrate that T(4) availability in liver tissue is not diminished
      during fasting, suggesting that in chicken thyroid hormone uptake by the liver is
      not affected by nutritional status.

PMID- 11997226
TI  - Structural and functional properties of a novel serine protease inhibiting
      peptide family in arthropods.
AB  - Recently, several arthropod peptides that belong to a new serine protease
      inhibitor family were discovered. Three members (HI, PMP-D2=LMCI-1 and PMP-C=LMCI
      2) were isolated from the migratory locust, Locusta migratoria. Five additional
      members (SGPI-1-5) were identified in the desert locust Schistocerca gregaria,
      and a heterodimeric serine protease inhibitor (pacifastin) was isolated from the
      hemolymph of the crayfish Pacifastacus leniusculus. The light chain of pacifastin
      constitutes the inhibitory subunit that has nine cysteine-rich domains (PLDs)
      that are homologous with the locust inhibitors. These locust inhibitors and PLDs
      share a conserved array of six cysteine residues (Cys-Xaa(9-12)-Cys-Asn-Xaa-Cys
      Xaa-Cys-Xaa(2-3)-Gly-Xaa(3-4)-Cys-Thr-Xaa(3)-Cys), which are involved in an
      identical disulfide bridge pattern (Cys(1)-Cys(4), Cys(2)-Cys(6), Cys(3)-Cys(5)).
      The solution structures of LMCI-1 and LMCI-2 showed a similar, compact, globular
      folding, which is unique within the group of the small 'canonical' inhibitors.
      Moreover, the reactive site, including the P1-P'1 bond was thoroughly
      investigated by means of synthetic variants. However, the biological function(s)
      of the locust inhibitors is (are) not fully understood. LMCI-1 and LMCI-2 were
      shown to inhibit the endogenous proteolytic activating cascade of
      prophenoloxidase. Northern blot analysis indicated that the genes encoding the
      SGPI precursors are differentially expressed in a time-, stage- and hormone
      dependent manner.

PMID- 11997227
TI  - Multiple control and dynamic response of the Xenopus melanotrope cell.
AB  - Some amphibian brain-melanotrope cell systems are used to study how neuronal and
      (neuro)endocrine mechanisms convert environmental signals into physiological
      responses. Pituitary melanotropes release alpha-melanophore-stimulating hormone
      (alpha-MSH), which controls skin color in response to background light stimuli.
      Xenopus laevis suprachiasmatic neurons receive optic input and inhibit
      melanotrope activity by releasing neuropeptide Y (NPY), dopamine (DA) and gamma
      aminobutyric acid (GABA) when animals are placed on a light background. Under
      this condition, they strengthen their synaptic contacts with the melanotropes and
      enhance their secretory machinery by upregulating exocytosis-related proteins
      (e.g. SNAP-25). The inhibitory transmitters converge on the adenylyl cyclase
      system, regulating Ca(2+) channel activity. Other messengers like thyrotropin
      releasing hormone (TRH) and corticotropin-releasing hormone (CRH, from the
      magnocellular nucleus), noradrenalin (from the locus coeruleus), serotonin (from
      the raphe nucleus) and acetylcholine (from the melanotropes themselves) stimulate
      melanotrope activity. Ca(2+) enters the cell and the resulting Ca(2+)
      oscillations trigger alpha-MSH secretion. These intracellular Ca(2+) dynamics can
      be described by a mathematical model. The oscillations travel as a wave through
      the cytoplasm and enter the nucleus where they may induce the expression of genes
      involved in biosynthesis and processing (7B2, PC2) of pro-opiomelanocortin (POMC)
      and release (SNAP-25, munc18) of its end-products. We propose that various
      environmental factors (e.g. light and temperature) act via distinct brain centers
      in order to release various neuronal messengers that act on the melanotrope to
      control distinct subcellular events (e.g. hormone biosynthesis, processing and
      release) by specifically shaping the pattern of melanotrope Ca(2+) oscillations.

PMID- 11997228
TI  - Regulation of neurons in the suprachiasmatic nucleus of Xenopus laevis.
AB  - In the amphibian Xenopus laevis, suprachiasmatic melanotrope-inhibiting neurons
      (SMINs) play an important role in the regulation of the background adaptation
      process. In this study, we investigated the innervation of the SMINs at the light
      and electron- microscopical level. Immunocytochemistry in combination with
      confocal laser scanning microscopy revealed co-existence of neuropeptide Y (NPY)
      and synaptobrevin in spots in the direct vicinity of the SMINs, suggesting the
      existence of NPY-containing synapses on these cells. At the ultrastructural
      level, the SMINs showed a high degree of plasticity, containing more electron
      dense vesicles and a larger extent of RER in white- than in black-adapted
      animals. In black-adapted animals, symmetric synapses (Gray type II) were
      observed on the soma of the SMINs, suggesting an inhibitory input to these cells.
      The synaptic profiles contained electron-lucent and electron-dense vesicles,
      indicating the involvement of both a classical neurotransmitter and a
      neuropeptide (possibly NPY) in this input. In white-adapted animals, synapses
      were only found at some distance from the SMIN somata. Our findings indicate a
      striking plasticity of the innervation of the SMINs in relation to background
      adaptation and support the hypothesis that the SMINs are innervated by NPY
      containing interneurons that inhibit SMIN activity in black-adapted animals.

PMID- 11997229
TI  - Arctic spring: hormone-behavior interactions in a severe environment.
AB  - Arctic breeding birds arrive on their nesting grounds in spring when weather
      conditions may still be extreme (low temperature, snow). The brief Arctic summer
      requires that they begin breeding as early as possible to take advantage of the
      ephemeral abundance of food to feed young. Failure to adjust to the local
      phenology results in drastically reduced reproductive success. Hormone-behavior
      adaptations may have evolved that maximize survival and reproductive success in
      the Arctic. It has been shown that the interrelationship of testosterone and
      territorial aggression, as birds arrive on the Arctic breeding grounds, varies
      according to species and locality. In some, territoriality is extremely brief
      following which birds become apparently refractory to the effects of
      testosterone. Others are territorial throughout the breeding season, but the
      dependence of these behaviors upon activation by testosterone is lost. Extensive
      data also indicate that Arctic birds modulate the adrenocortical response to
      acute stress. Secretion of corticosterone in response to a standardized capture
      stress protocol, used to mimic acute stress as a function of local environmental
      conditions, varies with the stage in the breeding cycle. Arctic breeding birds
      modulate the sensitivity of the adrenocortical response to acute stress at both
      the population and individual levels. These modulations are thought to be
      adaptations to allow the onset of territorial behavior and breeding in the face
      of potentially stressful conditions. Behavioral and physiological responses to
      corticosterone treatment are also diminished. A combination of these two hormone
      behavior interrelationships can form important components of the proximate
      mechanisms by which birds, and other vertebrates, breed successfully in a severe
      and often capricious environment.

PMID- 11997230
TI  - Does prolactin affect steroid secretion by isolated rainbow trout ovarian cells?
AB  - The in vitro secretion of progesterone (P(4)), androgen (A) and estradiol (E(2))
      by follicular cells, isolated monthly from the rainbow trout ovaries during the
      whole annual cycle, was studied. Cells were cultured as monolayers in control and
      prolactin (PRL) supplemented media. E(2) secretion showed two distinct maxima in
      September and January: 4959+/-220 pg/ml and 3166+/-121 pg/ml, respectively, i.e.
      during vitellogenesis and before the spawning time. PRL had a significant (16%)
      suppressive effect on E(2) secretion when the level of secreted steroid was at
      its highest (4167+/-193 pg/ml) at the end of vitellogenesis and by 32% (2157+/
      124 pg/ml), before ovulation. Increased P(4) levels observed in February (988+/
      69 pg/ml) and March (2008+/-74 pg/ml) may be connected with the need for a
      substrate for the synthesis of 17alpha20betaOH-P (MIS). At this time, the
      secretion of P(4) was also suppressed by PRL and was reduced to 1395+/-78 pg/ml.
      Our results indicate that PRL may play a role in fish reproduction.

PMID- 11997231
TI  - Internalization of the chicken growth hormone receptor complex and its effect on
      biological functions.
AB  - In the chicken, as in mammals, GH is a pleiotropic cytokine that plays a central
      role in growth differentiation and metabolism by altering gene expression in
      target cells. In the growing and adult chicken it stimulates gene expression of
      IGF-I and inhibits gene transcription of the type III deiodinating enzyme (D3)
      and by doing so also increases T(3) concentrations. GH binding to its receptor
      leads to internalization of the GH-GHR complex to the Golgi apparatus. This
      process is linked to the episodic release pattern of GH during growth. At the
      same time, a sharp decline of the expression of cGHR occurs at hatching. An in
      vitro study using a COS-7 cell line transfected with the cDNA of the chicken GHR,
      revealed that GHR immunofluorescence was found in the perinuclear region and on
      the plasma membrane. Following GH-induced internalization, GH and GHR were
      colocalized in endocytic and later in large lysosomal vesicles. Neither receptor
      nor ligand was transferred to the nucleus as confirmed by confocal laser
      microscopy. The JAK/STAT pathway however, as reported for mammalian GH receptors,
      mediated GH-induced gene transcription in chickens.

PMID- 11997232
TI  - Nicotinic acid adenine dinucleotide phosphate: a new intracellular second
      messenger?
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is one of the most potent
      stimulators of intracellular Ca2+ release known to date. The role of the NAADP
      system in physiological processes is being extensively investigated at the
      present time. Exciting new discoveries in the last 5 years suggest that the NAADP
      regulated system may have a significant role in intracellular Ca2+ signaling. The
      NAADP receptor and its associated Ca2+ pool have been hypothesized to be
      important in several physiological processes including fertilization, T cell
      activation, and pancreatic secretion. However, whether NAADP is a new second
      messenger or a tool for the discovery of a new Ca2+ channel is still an
      unanswered question.

PMID- 11997233
TI  - Isolated mouse pancreatic beta-cells show cell-specific temporal response
      pattern.
AB  - The length of the silent lag time before elevation of the cytosolic free Ca2+
      concentration ([Ca2+]i) differs between individual pancreatic beta-cells. One
      important question is whether these differences reflect a random phenomenon or
      whether the length of lag time is inherent in the individual beta-cell. We
      compared the lag times, initial dips, and initial peak heights for [Ca2+]i from
      two consecutive glucose stimulations (with either 10 or 20 mM glucose) in
      individual ob/ob mouse beta-cells with the fura 2 technique in a
      microfluorimetric system. There was a strong correlation between the lengths of
      the lag times in each beta-cell (10 mM glucose: r = 0.94, P < 0.001; 20 mM
      glucose: r = 0.96, P < 0.001) as well as between the initial dips in [Ca2+]i (10
      mM glucose: r = 0.93, P < 0.001; 20 mM glucose: r = 0.79, P < 0.001) and between
      the initial peak heights (10 mM glucose: r = 0.51, P < 0.01; 20 mM glucose: r =
      0.77, P < 0.001). These data provide evidence that the response pattern,
      including both the length of the lag time and the dynamics of the subsequent
      [Ca2+]i, is specific for the individual beta-cell.

PMID- 11997234
TI  - Lipopolysaccharide stimulation of ERK1/2 increases TNF-alpha production via Egr
      1.
AB  - Lipopolysaccharide (LPS) is a potent activator of tumor necrosis factor-alpha
      (TNF-alpha) production by macrophages. LPS stimulates the phosphorylation of
      extracellular signal-regulated kinase (ERK) 1/2 and increases TNF-alpha mRNA and
      protein accumulation in RAW 264.7 murine macrophages. However, the role of ERK1/2
      activation in mediating LPS-stimulated TNF-alpha production is not well
      understood. Inhibition of ERK1/2 activation with PD-98059 or overexpression of
      dominant negative ERK1/2 decreased LPS-induced TNF-alpha mRNA quantity. LPS
      rapidly increased early growth response factor (Egr)-1 binding to the TNF-alpha
      promoter; this response was blunted in cells treated with PD-98059 or transfected
      with dominant-negative ERK1/2. Using a chloramphenicol acetyltransferase reporter
      gene linked to the Egr-1 promoter, we show that LPS increased Egr-1 promoter
      activity via an ERK1/2-dependent mechanism. These results delineate the role of
      ERK1/2 activation of Egr-1 activity in mediating LPS-induced increases in TNF
      alpha mRNA expression in macrophages.

PMID- 11997235
TI  - An NAD(P)H oxidase regulates growth and transcription in melanoma cells.
AB  - Malignant melanoma cells spontaneously generate reactive oxygen species (ROS)
      that promote constitutive activation of the transcription factor nuclear factor
      kappaB (NF-kappaB). Although antioxidants and inhibitors of NAD(P)H oxidases
      significantly reduce constitutive NF-kappaB activation and suppress cell
      proliferation (11), the nature of the enzyme responsible for ROS production in
      melanoma cells has not been determined. To address this issue, we now have
      characterized the source of ROS production in melanoma cells. We report that ROS
      are generated by isolated, cytosol-free melanoma plasma membranes, with
      inhibition by NAD(P)H oxidase inhibitors. The p22(phox), gp91(phox), and
      p67(phox) components of the human phagocyte NAD(P)H oxidase and the gp91(phox)
      homolog NOX4 were demonstrated in melanomas by RT-PCR and sequencing, and protein
      product for both p22(phox) and gp91(phox) was detected in cell membranes by
      immunoassay. Normal human epidermal melanocytes expressed only p22(phox) and
      NOX4. Melanoma proliferation was reduced by NAD(P)H oxidase inhibitors and by
      transfection of antisense but not sense oligonucleotides for p22(phox) and NOX4.
      Also, the flavoprotein inhibitor diphenylene iodonium inhibited constitutive DNA
      binding of nuclear protein to the NF-kappaB and cAMP-response element consensus
      oligonucleotides, without affecting DNA binding activity to activator protein-1
      or OCT-1. This suggests that ROS generated in autocrine fashion by an NAD(P)H
      oxidase may play a role in signaling malignant melanoma growth.

PMID- 11997236
TI  - Neuroprotective role of delta-opioid receptors in cortical neurons.
AB  - We recently demonstrated that delta-opioid receptor (DOR) activation protects
      cortical neurons against glutamate-induced injury. Because glutamate is a
      mediator of hypoxic injury in neurons, we hypothesized that DOR is involved in
      neuroprotection during O2 deprivation and that its activation/inhibition may
      alter neuronal susceptibility to hypoxic stress. In this work, we tested the
      effect of opioid receptor activation and inhibition on cultured cortical neurons
      in hypoxia (1% O2). Cell injury was assessed by lactate dehydrogenase release,
      morphology-based quantification, and live/dead staining. Our results show that 1)
      immature neurons (days 4 and 6) were not significantly injured by hypoxia until
      72 h of exposure, whereas day 8 neurons were injured after only 24-h hypoxia; 2)
      DOR inhibition (naltrindole) caused neuronal injury in both day 4 and day 8
      normoxic cultures and further augmented hypoxic injury in these neurons; 3) DOR
      activation ([D-Ala2,D-Leu5]enkephalin) reduced neuronal injury in day 8 cultures
      after 24 h of normoxic or hypoxic exposure and attenuated naltrindole-induced
      injury with prolonged exposure; and 4) mu- or kappa-opioid receptor inhibition
      (beta-funaltrexamine or nor-binaltorphimine) had little effect on neurons in
      either normoxic or hypoxic conditions. Collectively, these data suggest that DOR
      plays a crucial role in neuroprotection in normoxic and hypoxic environments.

PMID- 11997237
TI  - Role of VASP in reestablishment of epithelial tight junction assembly after Ca2+
      switch.
AB  - Epithelial permeability is tightly regulated by intracellular messengers.
      Critical to maintaining barrier integrity is the formation of tight junction
      complexes. A number of signaling pathways have been implicated in tight junction
      biogenesis; however, the precise molecular mechanisms are not fully understood. A
      growing body of evidence suggests a role for intracellular cAMP in tight junction
      assembly. Using an epithelial model, we investigated the role of cAMP signal
      transduction in barrier recovery after Ca2+ switch. Our data demonstrate that
      elevation of intracellular cAMP levels significantly enhanced barrier recovery
      after Ca2+ switch. Parallel experiments revealed that epithelial barrier recovery
      is diminished by H-89, a specific and potent inhibitor of cAMP-dependent protein
      kinase (protein kinase A) activity. Of the possible PKA effector proteins, the
      vasodilator-stimulated phosphoprotein (VASP) is an attractive candidate, since it
      has been implicated in actin-binding and cross-linking functions. We therefore
      hypothesized that VASP may play a role in the cAMP-mediated regulation of
      epithelial junctional reassembly after Ca2+ switch. We demonstrate here that VASP
      is phosphorylated via a PKA-dependent process under conditions that enhance
      barrier recovery. Confocal laser scanning microscopy studies revealed that VASP
      localizes with ZO-1 at the tight junction and at cell-cell borders and that
      phospho-VASP appears at the junction after Ca2+ switch. Subsequent transfection
      studies utilizing epithelial cells expressing truncated forms of VASP abnormal in
      oligomerization or actin-binding activity revealed a functional diminution of
      barrier recovery after Ca2+ chelation. Our present studies suggest that VASP may
      provide a link between cAMP signal transduction and epithelial permeability.

PMID- 11997238
TI  - Characterization of L-glutamine transport by a human neuroblastoma cell line.
AB  - This study characterized the Na+-dependent transport of L-glutamine by a human
      neuroblastoma cell line, SK-N-SH. The Na+-dependent component represented >95% of
      the total glutamine uptake. Kinetic studies showed a single saturable high
      affinity carrier with a Michaelis constant (K(m)) of 163 +/- 23 microM and a
      maximum transport velocity (Vmax) of 13,713 +/- 803 pmol x mg protein(-1) x min(
      1). Glutamine uptake was markedly inhibited in the presence of L-alanine, L
      asparagine, and L-serine. Li+ did not substitute for Na+. These data show that L
      glutamine is predominantly taken up through system ASC. Glutamine deprivation
      resulted in the decrease of glutamine transport by a mechanism that decreased
      Vmax without affecting K(m). The expression of the system ASC subtype ASCT2
      decreased in the glutamine-deprived group, whereas glutamine deprivation did not
      induce changes in system ASC subtype ASCT1 mRNA expression. Adaptive increases in
      Na+-dependent glutamate, Na+-dependent 2-(methylamino)isobutyric acid, and Na+
      independent leucine transport were observed under glutamine-deprived conditions,
      which were completely blocked by actinomycin D and cycloheximide. These
      mechanisms may allow cells to survive and even grow under nutrient-deprived
      conditions.

PMID- 11997239
TI  - IL-1beta-induced production of metalloproteinases by synovial cells depends on
      gap junction conductance.
AB  - Synovial cells can form networks connected by gap junctions. The purpose of this
      study was to obtain evidence for a necessary role of gap junction intercellular
      communication in protein secretion by synovial cells. We developed a novel assay
      to measure the enzymatic activity of metalloproteinases (MMPs) produced by
      synovial cells in response to interleukin-1beta (IL-1beta) and employed the assay
      to explore the biological function of gap junctions. IL-1beta produced a dose
      dependent increase in MMP activity that was blocked by exposure to the gap
      junction inhibitors 18alpha-glycyrrhetinic acid and octanol for as few as 50 min.
      The inhibitors produced an immediate and marked reduction in intercellular
      communication, as assessed by transient current analysis using the nystatin
      perforated-patch method. These observations suggest that communication through
      gap junctions early in IL-1beta signal transduction is critical to the process of
      cytokine-regulated secretion of MMPs by synovial cells.

PMID- 11997240
TI  - Hypertonicity increases cAMP in PMN and blocks oxidative burst by PKA-dependent
      and -independent mechanisms.
AB  - Hypertonic stress (HS) suppresses neutrophil (PMN) functions. We studied the
      underlying mechanism and found that HS rapidly (<1 min) increased intracellular
      cAMP levels by up to sevenfold. cAMP levels correlated with applied hypertonicity
      and the degree of neutrophil suppression. HS and cAMP-elevating drugs (forskolin
      and dibutyryl cAMP-acetoxymethyl ester) similarly suppressed extracellular signal
      regulated kinase (ERK) and p38 mitogen-activated protein kinase activation and
      superoxide formation in response to N-formylmethionyl-leucyl-phenylalanine (fMLP)
      stimulation. Inhibition of cAMP-dependent protein kinase A (PKA) with H-89
      abrogated the suppressive effects of HS, restoring fMLP-induced ERK and p38
      activation and superoxide formation. Inhibition of phosphodiesterase with 3
      isobutyl-1-methylxanthine augmented cAMP accumulation and the suppressive effects
      of HS, while inhibition of adenylyl cyclase with MDL-12330A abolished these
      effects. These findings suggest that HS-activated cAMP/PKA signaling inhibits
      superoxide formation by intercepting fMLP-induced activation steps upstream of
      ERK and p38. In contrast to its effects in the presence of moderate hypertonicity
      levels (40 mM), H-89 was unable to rescue neutrophil functions from suppression
      by higher hypertonicity levels (100 mM), indicating that more severe HS
      suppresses neutrophils via secondary PKA-independent mechanisms.

PMID- 11997241
TI  - Changes in contractile properties of skeletal muscle during developmentally
      programmed atrophy and death.
AB  - Skeletal muscle atrophy and death are protracted processes that accompany aging
      and pathological insults in mammals. The intersegmental muscles (ISMs) from the
      tobacco hawkmoth Manduca sexta are composed of giant fibers that undergo distinct
      hormonally-regulated programs of atrophy and death at the end of metamorphosis.
      Atrophy occurs during the 3 days preceding adult emergence and results in a 40%
      reduction of mass, whereas death takes place during the subsequent 30 h and
      results in the complete loss of the fibers. There are no significant changes in
      tetanic force or calcium sensitivity in skinned fiber preparations during
      atrophy. However, the size of caffeine-induced contractions fell by about 50%.
      With the onset of the death phase, dramatic reductions occur in ISM: tetanic
      force, twitch amplitude, resting potential, caffeine-induced contractions,
      calcium sensitivity, and Hill coefficients. Several lines of evidence suggest
      that ISM atrophy is caused by an increase in protein turnover without significant
      modification of fiber organization. In contrast, ISM death is accompanied by
      disorganization of the contractile apparatus and concomitant loss of contractile
      function.

PMID- 11997242
TI  - Functional characterization of human NBC4 as an electrogenic Na+-HCO
      cotransporter (NBCe2).
AB  - We have functionally characterized Na+-driven bicarbonate transporter (NBC)4,
      originally cloned from human heart by Pushkin et al. (Pushkin A, Abuladze N,
      Newman D, Lee I, Xu G, and Kurtz I. Biochem Biophys Acta 1493: 215-218, 2000). Of
      the four NBC4 variants currently present in GenBank, our own cloning efforts
      yielded only variant c. We expressed NBC4c (GenBank accession no. AF293337) in
      Xenopus laevis oocytes and assayed membrane potential (Vm) and pH regulatory
      function with microelectrodes. Exposing an NBC4c-expressing oocyte to a solution
      containing 5% CO2 and 33 mM HCO elicited a large hyperpolarization, indicating
      that the transporter is electrogenic. The initial CO2-induced decrease in
      intracellular pH (pH(i)) was followed by a slow recovery that was reversed by
      removing external Na+. Two-electrode voltage clamp of NBC4c-expressing oocytes
      revealed large HCO- and Na+-dependent currents. When we voltage clamped V(m) far
      from NBC4c's estimated reversal potential (E(rev)), the pH(i) recovery rate
      increased substantially. Both the currents and pH(i) recovery were blocked by 200
      microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). We estimated the
      transporter's HCO:Na+ stoichiometry by measuring E(rev) at different
      extracellular Na+ concentration ([Na+]o) values. A plot of E(rev) against
      log[Na+]o was linear, with a slope of 54.8 mV/log[Na+]o. This observation, as
      well as the absolute E(rev) values, are consistent with a 2:1 stoichiometry. In
      conclusion, the behavior of NBC4c, which we propose to call NBCe2-c, is similar
      to that of NBCe1, the first electrogenic NBC.

PMID- 11997243
TI  - Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the
      release of cytochrome c.
AB  - We have shown previously that depletion of polyamines delays apoptosis induced by
      camptothecin in rat intestinal epithelial cells (IEC-6). Mitochondria play an
      important role in the regulation of apoptosis in mammalian cells because
      apoptotic signals induce mitochondria to release cytochrome c. The latter
      interacts with Apaf-1 to activate caspase-9, which in turn activates downstream
      caspase-3. Bcl-2 family proteins are involved in the regulation of cytochrome c
      release from mitochondria. In this study, we examined the effects of polyamine
      depletion on the activation of the caspase cascade, release of cytochrome c from
      mitochondria, and expression and translocation of Bcl-2 family proteins. We
      inhibited ornithine decarboxylase, the first rate-limiting enzyme in polyamine
      synthesis, with alpha-difluoromethylornithine (DFMO) to deplete cells of
      polyamines. Depletion of polyamines prevented camptothecin-induced release of
      cytochrome c from mitochondria and decreased the activity of caspase-9 and
      caspase-3. The mitochondrial membrane potential was not disrupted when cytochrome
      c was released. Depletion of polyamines decreased translocation of Bax to
      mitochondria during apoptosis. The expression of antiapoptotic proteins Bcl-x(L)
      and Bcl-2 was increased in DFMO-treated cells. Caspase-8 activity and cleavage of
      Bid were decreased in cells depleted of polyamines. These results suggest that
      polyamine depletion prevents IEC-6 cells from apoptosis by preventing the
      translocation of Bax to mitochondria, thus preventing the release of cytochrome
      c.

PMID- 11997244
TI  - Myosin light chain phosphorylation facilitates in vivo myosin filament reassembly
      after mechanical perturbation.
AB  - Phosphorylation of the 20-kDa regulatory myosin light chain (MLC) of smooth
      muscle is known to cause monomeric myosins in solution to self-assemble into
      thick filaments. The role of MLC phosphorylation in thick filament formation in
      intact muscle, however, is not clear. It is not known whether the phosphorylation
      is necessary to initiate thick filament assembly in vivo. Here we show, by using
      a potent inhibitor of MLC kinase (wortmannin), that the MLC phosphorylation and
      isometric force in trachealis muscle could be abolished without affecting calcium
      transients. By measuring cross-sectional densities of the thick filaments
      electron microscopically, we also show that inhibition of MLC phosphorylation
      alone did not cause disassembly of the filaments. The unphosphorylated thick
      filaments, however, partially dissolved when the muscle was subjected to
      oscillatory strains (which caused a 25% decrease in the thick filament density).
      The postoscillation filament density recovered to the preoscillation level only
      when wortmannin was removed and the muscle was stimulated. The data suggest that
      in vivo thick filament reassembly after mechanical perturbation is facilitated by
      the cyclic MLC phosphorylation associated with repeated stimulation.

PMID- 11997245
TI  - Effects of glucose on contractile function, [Ca2+]i, and glycogen in isolated
      mouse skeletal muscle.
AB  - Extensor digitorum longus muscles were stimulated to contract to fatigue and
      allowed to recover for 2 h in the absence or presence of 5.5 or 11 mM
      extracellular glucose. This was followed by a second fatigue run, which ended
      when the absolute force was the same as at the end of the first run. During the
      first fatigue run, the fluorescence ratio for indo 1 increased [reflecting an
      increase in myoplasmic free Ca2+ concentration ([Ca2+]i)] during the initial
      tetani, peaking at approximately 115% of the first tetanic value, followed by a
      continuous decrease to approximately 90% at fatigue. During the first fatigue
      run, myofibrillar Ca2+ sensitivity was significantly decreased. During the second
      run, the number of tetani was 57 +/- 6% of initial force in muscles that
      recovered in the absence of glucose and 110 +/- 6 and 119 +/- 2% of initial force
      in muscles that recovered in 5.5 and 11 mM glucose, respectively. Fluorescence
      ratios during the first, peak, and last tetani did not differ significantly
      between the first and second fatigue runs during any of the three conditions.
      Glycogen decreased by almost 50% during the first fatigue run and did not change
      further after recovery in the absence of glucose. After recovery in the presence
      of 5.5 and 11 mM glucose, glycogen increased 32 and 42% above the nonstimulated
      control value (P < 0.01). These data demonstrate that extracellular glucose
      delays the decrease of tetanic force and [Ca2+]i during fatiguing stimulation and
      that glycogen supercompensation following contraction can occur in the absence of
      insulin.

PMID- 11997246
TI  - Ligand-regulated secretion of recombinant annexin V from cultured thyroid
      epithelial cells.
AB  - The exposure of anionic phospholipids on the external surface of injured
      endothelial cells and activated platelets is a primary biological signal to
      initiate blood coagulation. Disease conditions that promote the formation of
      ectopic thrombi result in tissue ischemia. Annexins, Ca2+-dependent anionic
      phospholipid binding proteins, are potential therapeutic agents for the
      inhibition of coagulation. We have designed a transgene that targets secretion of
      annexin V from cultured thyroid cells under the control of doxycycline. Our
      results indicate that annexin V in the endoplasmic reticulum (ER)/Golgi lumen
      does not affect the synthesis, processing, and secretion of thyroglobulin. ER
      luminal Ca2+ was moderately increased and can be released by inositol 1,4,5
      trisphosphate. Our study demonstrates that targeting and secretion of annexin V
      through the secretory pathway of mammalian cells does not adversely affect
      cellular function. Regulated synthesis and release of annexin V may exert
      anticoagulatory and anti-inflammatory effects systemically and may prove useful
      in further developing therapeutic strategies for conditions including
      antiphospholipid syndrome.

PMID- 11997247
TI  - Novel regulation of adrenomedullin receptor by PDGF: role of receptor activity
      modifying protein-3.
AB  - Receptor activity modifying protein-3 (RAMP-3) has been shown to complex with the
      calcitonin receptor-like receptor, establishing a functional receptor for
      adrenomedullin (AM). AM exhibits potent antiproliferative and antimigratory
      effects on rat mesangial cells (RMCs). In this study we investigated the effect
      of platelet-derived growth factor (PDGF) on RAMP-3 expression in RMCs. We show
      here that PDGF-BB stimulates RAMP-3 mRNA expression in a concentration-dependent
      manner. Pretreatment with actinomycin-D and alpha-amanitin demonstrates that this
      effect is independent of new RNA synthesis. Furthermore, PDGF increased the half
      life of RAMP-3 mRNA from 66.5 to 331.6 min. Using selective inhibitors, our
      results also indicate that the increase in RAMP-3 mRNA is mitogen-activated
      protein kinase (MAPK) kinase (MEK)/MAPK and p38 MAPK dependent. PDGF also caused
      a corresponding elevation in membrane-associated RAMP-3 protein. Associated with
      this increase, PDGF pretreatment led to a significantly higher AM-mediated
      adenylate cyclase activity, suggesting a functional consequence for the PDGF
      induced increase in RAMP-3 expression. Taken together, these data identify PDGF
      dependent regulation of RAMP-3 expression as a possible mechanism for modulating
      the responsiveness of the mesangial cell to AM.

PMID- 11997248
TI  - Decreased 5alpha-dihydrotestosterone catabolism suppresses T lymphocyte functions
      in males after trauma-hemorrhage.
AB  - Trauma-hemorrhage produces profound immunosuppression in males but not in
      proestrus females. Prior castration or flutamide treatment of males following
      trauma-hemorrhage prevents immunosuppression, implicating 5alpha
      dihydrotestosterone for the immunosuppressive effects. 5alpha
      dihydrotestosterone, a high-affinity androgen receptor-binding steroid, is
      synthesized in tissues as needed and seldom accumulates. The presence of
      steroidogenic enzymes in T lymphocytes suggests both synthesis and catabolism of
      5alpha-dihydrotestosterone. We hypothesized, therefore, that the basis for high
      5alpha-dihydrotestosterone activity in T lymphocytes of males following trauma
      hemorrhage is due to decreased catabolism. Accordingly, catabolism of 5alpha
      dihydrotestosterone was assessed in splenic T lymphocytes by examining the
      activity and expression of enzymes involved. Analysis showed increased synthesis
      and decreased catabolism of 5alpha-dihydrotestosterone in intact male T
      lymphocytes following trauma-hemorrhage. In contrast, reduced 5alpha-reductase
      activity and increased expression of 17beta-hydroxysteroid dehydrogenase
      oxidative isomers suggest inactivation of 5alpha-dihydrotestosterone in
      precastrated males. Thus our study suggests increased synthesis and decreased
      catabolism of 5alpha-dihydrotestosterone as a reason for loss of T lymphocyte
      functions in intact males following trauma-hemorrhage, as evidenced by decreased
      release of interleukin-2 and -6.

PMID- 11997249
TI  - Arachidonic acid mediates dual effect of TNF-alpha on Ca2+ transients and
      contraction of adult rat cardiomyocytes.
AB  - Tumor necrosis factor (TNF)-alpha has a biphasic effect on heart contractility
      and stimulates phospholipase A2 (PLA2) in cardiomyocytes. Because arachidonic
      acid (AA) exerts a dual effect on intracellular Ca2+ concentration ([Ca2+]i)
      transients, we investigated the possible role of AA as a mediator of TNF-alpha on
      [Ca2+]i transients and contraction with electrically stimulated adult rat cardiac
      myocytes. At a low concentration (10 ng/ml) TNF-alpha produced a 40% increase in
      the amplitude of both [Ca2+]i transients and contraction within 40 min. At a high
      concentration (50 ng/ml) TNF-alpha evoked a biphasic effect comprising an initial
      positive effect peaking at 5 min, followed by a sustained negative effect leading
      to 50-40% decreases in [Ca2+]i transients and contraction after 30 min. Both the
      positive and negative effects of TNF-alpha were reproduced by AA and blocked by
      arachidonyltrifluoromethyl ketone (AACOCF3), an inhibitor of cytosolic PLA2.
      Lipoxygenase and cyclooxygenase inhibitors reproduced the high-dose effects of
      TNF-alpha and AA. The negative effects of TNF-alpha and AA were also reproduced
      by sphingosine and were abrogated by the ceramidase inhibitor n
      oleoylethanolamine. These results point out the key role of the cytosolic PLA2/AA
      pathway in mediating the contractile effects of TNF-alpha.

PMID- 11997250
TI  - Regulation of apoptosis in the endocardial cushions of the developing chick
      heart.
AB  - During the early stages of heart development, there are two main foci of cell
      death: outflow tract (OT) and atrioventricular (AV) endocardial cushions. These
      tissues contribute to the septa and valves of the mature heart and receive cell
      populations from neural crest (NC) cell migration and epicardial cell invasion.
      We examined embryonic chick hearts for expression, in the cushions, of bcl-2
      family members, caspase-9, and the caspase substrate poly(ADP-ribose) polymerase.
      Antiapoptotic bcl-2 is expressed heavily in the OT and AV regions throughout
      embryonic days (ED) 4-7, with a decrease in levels at ED 4 and 5 in OT and AV
      cushions, respectively. Proapoptotic bax predominantly associated with the prongs
      of the NC-derived aorticopulmonary (AP) septum but was expressed throughout the
      AV cushions. Proapoptotic bak also associated with the prongs of the AP septum in
      the OT, while protein levels were upregulated at ED 4-5 and 4-6 in OT and AV
      cushions, respectively. Bid expression showed a similar time course. We found the
      10-kDa cleavage fragment of active caspase-9 at ED 4-8 and 5-8 in OT and AV
      cushions, respectively, and the 24-kDa cleavage fragment of poly(ADP-ribose)
      polymerase throughout ED 3-8 and 7-8 in OT and AV cushions, respectively. Caspase
      3 cleavage occurred throughout the time period examined. Using cushion cell
      cultures, we found that inhibitors of caspases-3 and -9 and a universal caspase
      inhibitor significantly reduced apoptosis, as did retroviral overexpression of
      bcl-2 using an RCAS expression vector. Premigratory NC cells were fluorescently
      labeled in vivo with 1,1-didodecyl-3,3,3',3'-tetramethylindocarbocyanine.
      Subsequent nuclear staining of cushion cells with 4,6-diamidino-2-phenylindole
      revealed the presence of apoptotic nuclei in the NC cells in the OT cushions and
      in the prongs of the AP septum. These results demonstrate a developmentally
      regulated role for the bcl-2 and the caspase families of molecules in the
      endocardial cushions of the developing heart and lend support to the possibility
      that some of the dying cells in the cushions are derived from the NC.

PMID- 11997252
TI  - Structural and functional relationships between Ca2+ puffs and mitochondria in
      Xenopus oocytes.
AB  - Ca2+ uptake and release from endoplasmic reticulum (ER) and mitochondrial Ca2+
      stores play important physiological and pathological roles, and these processes
      are shaped by interactions that depend on the structural intimacy between these
      organelles. Here we investigate the morphological and functional relationships
      between mitochondria, ER, and the sites of intracellular Ca2+ release in Xenopus
      laevis oocytes by combining confocal imaging of local Ca2+ release events ("Ca2+
      puffs") with mitochondrial localization visualized using vital dyes and
      subcellularly targeted fluorescent proteins. Mitochondria and ER are localized in
      cortical bands approximately 6-8 microm wide, with the mitochondria arranged as
      densely packed "islands" interconnected by discrete strands. The ER is
      concentrated more superficially than mitochondria, and the mean separation
      between Ca2+ puff sites and mitochondria is approximately 2.3 microm. However, a
      subpopulation of Ca2+ puff sites is intimately associated with mitochondria
      (approximately 28% within <600 nm), a greater number than expected if Ca2+ puff
      sites were randomly distributed. Ca2+ release sites close to mitochondria exhibit
      lower Ca2+ puff activity than Ca2+ puff sites in regions with lower mitochondrial
      density. Furthermore, Ca2+ puff sites in close association with mitochondria
      rarely serve as the sites for Ca2+ wave initiation. We conclude that mitochondria
      play important roles in regulating local ER excitability, Ca2+ wave initiation,
      and, thereby, spatial patterning of global Ca2+ signals.

PMID- 11997251
TI  - Sphingosine 1-phosphate induces Ca2+ transients and cytoskeletal rearrangement in
      C2C12 myoblastic cells.
AB  - In many cell systems, sphingosine 1-phosphate (SPP) increases cytosolic Ca2+
      concentration ([Ca2+]i) by acting as intracellular mediator and extracellular
      ligand. We recently demonstrated (Meacci E, Cencetti F, Formigli L, Squecco R,
      Donati C, Tiribilli B, Quercioli F, Zecchi-Orlandini S, Francini F, and Bruni P.
      Biochem J 362: 349-357, 2002) involvement of endothelial differentiation gene
      (Edg) receptors (Rs) specific for SPP in agonist-mediated Ca2+ response of a
      mouse skeletal myoblastic (C2C12) cell line. Here, we investigated the Ca2+
      sources of SPP-mediated Ca2+ transients in C2C12 cells and the possible
      correlation of ion response to cytoskeletal rearrangement. Confocal fluorescence
      imaging of C2C12 cells preloaded with Ca2+ dye fluo 3 revealed that SPP elicited
      a transient Ca2+ increase propagating as a wave throughout the cell. This
      response required extracellular and intracellular Ca2+ pool mobilization. Indeed,
      it was significantly reduced by removal of external Ca2+, pretreatment with
      nifedipine (blocker of L-type plasma membrane Ca2+ channels), and inositol 1,4,5
      trisphosphate [Ins(1,4,5)P3]-mediated Ca2+ pathway inhibitors. Involvement of
      EdgRs was tested with suramin (specific inhibitor of Edg-3). Fluorescence
      associated with Ins(1,4,5)P3Rs and L-type Ca2+ channels was evident in C2C12
      cells. SPP also induced C2C12 cell contraction. This event, however, was
      unrelated to [Ca2+]i increase, because the two phenomena were temporally shifted.
      We propose that SPP may promote C2C12 cell contraction through Ca2+-independent
      mechanisms.

PMID- 11997253
TI  - Maintenance of muscle mass is not dependent on the calcineurin-NFAT pathway.
AB  - In this study, the role of the calcineurin pathway in skeletal muscle atrophy and
      atrophy-reducing interventions was investigated in rat soleus muscles. Because
      calcineurin has been suggested to be involved in skeletal and cardiac muscle
      hypertrophy, we hypothesized that blocking calcineurin activity would eliminate
      beneficial effects of interventions that maintain muscle mass in the face of
      atrophy-inducing stimuli. Hindlimb suspension and spinal cord transection were
      used to induce atrophy, and intermittent reloading and exercise were used to
      reduce atrophy. Cyclosporin (CsA, 25 mg x kg(-1) x day(-1)) was administered to
      block calcineurin activity. Soleus muscles were studied 14 days after the onset
      of atrophy. CsA administration did not inhibit the beneficial effects of the two
      muscle-maintaining interventions, nor did it change muscle mass in control or
      atrophied muscles, suggesting that calcineurin does not play a role in regulating
      muscle size during atrophy. However, calcineurin abundance was increased in
      atrophied soleus muscles, and this was associated with nuclear localization of
      NFATc1 (a nuclear factor of activated T cells). Therefore, results suggest that
      calcineurin may be playing opposing roles during skeletal muscle atrophy and
      under muscle mass-maintaining conditions.

PMID- 11997254
TI  - Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of
      excitatory synapses.
AB  - Classical inwardly rectifying K+ channels (Kir2.0) are responsible for
      maintaining the resting membrane potential near the K+ equilibrium potential in
      various cells, including neurons. Although Kir2.3 is known to be expressed
      abundantly in the forebrain, its precise localization has not been identified.
      Using an antibody specific to Kir2.3, we examined the subcellular localization of
      Kir2.3 in mouse brain. Kir2.3 immunoreactivity was detected in a granular pattern
      in restricted areas of the brain, including the olfactory bulb (OB).
      Immunoelectron microscopy of the OB revealed that Kir2.3 immunoreactivity was
      specifically clustered on the postsynaptic membrane of asymmetric synapses
      between granule cells and mitral/tufted cells. The immunoprecipitants for Kir2.3
      obtained from brain contained PSD-95 and chapsyn-110, PDZ domain-containing
      anchoring proteins. In vitro binding assay further revealed that the COOH
      terminal end of Kir2.3 is responsible for the association with these anchoring
      proteins. Therefore, the Kir channel may be involved in formation of the resting
      membrane potential of the spines and, thus, would affect the response of N-methyl
      D-aspartic acid receptor channels at the excitatory postsynaptic membrane.

PMID- 11997255
TI  - Aspartate aminotransferase isotope exchange reactions: implications for
      glutamate/glutamine shuttle hypothesis.
AB  - Aspartate aminotransferase (AAT) catalyzes amino group transfer from glutamate
      (Glu) or aspartate (Asp) to a keto acid acceptor-oxaloacetate (OA) or alpha
      ketoglutarate (KG), respectively. Data presented here show that AAT catalyzes two
      partial reactions resulting in isotope exchange between 3H-labeled Glu or 3H
      labeled Asp and the cognate keto acid in the absence of the keto acid acceptor
      required for the net reaction. Tritiated keto acid product was detected by
      release of 3H2O from C-3 during base-induced enolization. Tritium released
      directly from C-2 (or C-3) by the enzyme was also evaluated and is a small
      fraction of that released because of exchange to the keto acid pool. Exchange is
      dependent on AAT concentration, time-dependent, proportional to the amino-to-keto
      acid ratio, and blocked by aminooxyacetate (AOA), an AAT inhibitor. Enzymatic
      conversion of [3H]KG to Glu by glutamic dehydrogenase (GDH) or of [3H]OA to
      malate by malic dehydrogenase (MDH) "protects" the label from release by base,
      showing that base-induced isotope release is from keto acid rather than a result
      of release during the exchange process. AAT isotope exchange is discussed in the
      context of the glutamate/glutamine shuttle hypothesis for astrocyte/neuron carbon
      cycling.

PMID- 11997256
TI  - Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through
      the Ca2+-sensing receptor.
AB  - We determined the effect of aromatic amino acid stimulation of the human
      extracellular Ca2+-sensing receptor (CaR) on intracellular Ca2+ concentration
      ([Ca2+]i) in single HEK-293 cells. Addition of L-phenylalanine or L-tryptophan
      (at 5 mM) induced [Ca2+]i oscillations from a resting state that was quiescent at
      1.8 mM extracellular Ca2+ concentration ([Ca2+]e). Each [Ca2+]i peak returned to
      baseline values, and the average oscillation frequency was approximately 1 min(
      1) at 37 degrees C. Oscillations were not induced or sustained if the [Ca2+]e was
      reduced to 0.5 mM, even in the continued presence of amino acid. Average
      oscillation frequency in response to an increase in [Ca2+]e (from 1.8 to 2.5-5
      mM) was much higher (approximately 4 min(-1)) than that induced by aromatic amino
      acids. Oscillations in response to [Ca2+]e were sinusoidal whereas those induced
      by amino acids were transient. Thus both amino acids and Ca2+, acting through the
      same CaR, produce oscillatory increases in [Ca2+]i, but the resultant oscillation
      pattern and frequency allow the cell to discriminate which agonist is bound to
      the receptor.

PMID- 11997257
TI  - In vivo microdialysis for determination of nasal liquid ion composition.
AB  - Airway surface liquid (ASL) contains substances important in mucociliary
      clearance and airway defense. Little is known about substance concentrations in
      ASL because of its small volume and sampling difficulties. We used in vivo
      microdialysis (IVMD) to sample liquid lining the nasal cavity without net volume
      removal and incorporated into IVMD a potential difference (PD) electrode to
      assess airway integrity. The cystic fibrosis (CF) mouse nasal epithelia exhibit
      ion transport defects identical to those in CF human airways and, thus, are a
      good model for CF disease. We determined that nasal liquid [Na+] (107 +/- 4 mM
      normal; 111 +/- 9 mM CF) and [Cl-] (120 +/- 6 mM normal; 122 +/- 4 mM CF) did not
      differ between genotypes. The nasal liquid [K+] (8.7 +/- 0.4 mM) was
      significantly less in normal than in CF mice (16.6 +/- 4 mM). IVMD accurately
      samples nasal liquid for ionic composition. The ionic composition of nasal liquid
      in the normal and CF mice is similar.

PMID- 11997258
TI  - ANG II and LPA induce Pyk2 tyrosine phosphorylation in intestinal epithelial
      cells: role of Ca2+, PKC, and Rho kinase.
AB  - The G protein-coupled receptor agonists angiotensin II (ANG II) and
      lysophosphatidic acid (LPA) rapidly induce tyrosine phosphorylation of the
      cytosolic proline-rich tyrosine kinase 2 (Pyk2) in IEC-18 intestinal epithelial
      cells. The combined Pyk2 tyrosine phosphorylation induced by phorbol 12,13
      dibutyrate, a direct agonist of protein kinase C (PKC), and ionomycin, a Ca2+
      ionophore, was equal to that induced by ANG II. Inhibition of either PKC or Ca2+
      signaling attenuated the effect of ANG II and LPA, although simultaneous
      inhibition of both pathways failed to completely abolish Pyk2 tyrosine
      phosphorylation. Cytochalasin D, which disrupts stress fibers, strongly inhibited
      the response of Pyk2 to ANG II or LPA. The distinct Rho-associated kinase (ROK)
      inhibitors HA-1077 and Y-27632, as well as the Rho inhibitor Clostridium
      botulinum C3 exoenzyme, also significantly attenuated ANG II- and LPA-stimulated
      Pyk2 tyrosine phosphorylation. Simultaneous inhibition of PKC, Ca2+, and either
      actin assembly or ROK completely abolished the Pyk2 response. Together, these
      results show that ANG II and LPA rapidly induce Pyk2 tyrosine phosphorylation in
      intestinal epithelial cells via separate Ca2+-, PKC-, and Rho-mediated pathways.

PMID- 11997259
TI  - Effect of reactive oxygen species on NH4+ permeation in Xenopus laevis oocytes.
AB  - To investigate the effects of reactive oxygen species (ROS) on NH4+ permeation in
      Xenopus laevis oocytes, we used intracellular double-barreled microelectrodes to
      monitor the changes in membrane potential (V(m)) and intracellular pH (pH(i))
      induced by a 20 mM NH4Cl-containing solution. Under control conditions, NH4Cl
      exposure induced a large membrane depolarization (to V(m) = 4.0 +/- 1.5 mV; n =
      21) and intracellular acidification [reaching a change in pH(i) (DeltapH(i)) of
      0.59 +/- 0.06 pH units in 12 min]; the initial rate of cell acidification
      (dpH(i)/dt) was 0.06 +/- 0.01 pH units/min. Incubation of the oocytes in the
      presence of H2O2 or beta-amyloid protein had no marked effect on the NH4Cl
      induced DeltapH(i). By contrast, in the presence of photoactivated rose bengal
      (RB), tert-butyl-hydroxyperoxide (t-BHP), or xanthine/xanthine oxidase (X/XO),
      the same experimental maneuver induced significantly greater DeltapH(i) and
      dpH(i)/dt. These increases in DeltapH(i) and dpH(i)/dt were prevented by the ROS
      scavengers histidine and desferrioxamine, suggesting involvement of the reactive
      species (1)DeltagO2 and.OH. Using the voltage-clamp technique to identify the
      mechanism underlying the ROS-measured effects, we found that RB induced a large
      increase in the oocyte membrane conductance (G(m)). This RB-induced G(m) increase
      was prevented by 1 mM diphenylamine-2-carboxylate (DPC) and by a low Na+
      concentration in the bath. We conclude that RB, t-BHP, and X/XO enhance NH4+
      influx into the oocyte via activation of a DPC-sensitive nonselective cation
      conductance pathway.

PMID- 11997260
TI  - V-type H+-ATPase in the human eccrine sweat duct: immunolocalization and
      functional demonstration.
AB  - We investigated for the presence of a vacuolar-type H+-ATPase (V-ATPase) in the
      human eccrine sweat duct (SD). With the use of immunocytochemistry, an anti-V-
      ATPase antibody showed a strong staining at the apical membrane and a weaker one
      in the cytoplasm. Cold preservation followed by rewarming did not alter this
      staining pattern. With the use of the pH-sensitive dye 2',7'-bis(2-carboxyethyl)
      5(6)-carboxyfluorescein on isolated and perfused straight SD under HCO-free
      conditions and in the absence of Na+, proton extrusion was determined from the
      recovery rate of intracellular pH (dpH(i)/dt) following an acid load. Oligomycin
      (25 microM), an inhibitor of F-type ATPases, decreased dpH(i)/dt by 88 +/- 6%,
      suggesting a role for an ATP-dependent process involved in pH(i) recovery.
      Moreover, dpH(i)/dt was inhibited at 95 +/- 3% by 100 nM luminal concanamycin A,
      a specific inhibitor of V-ATPases, whereas 10 microM bafilomycin A1, another
      specific inhibitor of V-ATPases, was required to decrease dpH(i)/dt by 73%. These
      results strongly suggest that a V-ATPase is involved in proton secretion in the
      human eccrine SD.

PMID- 11997261
TI  - Direct inhibition of the cloned Kv1.5 channel by AG-1478, a tyrosine kinase
      inhibitor.
AB  - The action of tyrphostin AG-1478, a potent protein tyrosine kinase (PTK)
      inhibitor, on rat brain Kv1.5 channels (Kv1.5) stably expressed in Chinese
      hamster ovary cells was investigated using the whole cell patch-clamp technique.
      AG-1478 rapidly and reversibly inhibited Kv1.5 currents at 50 mV in a
      concentration-dependent manner with an IC50 of 9.82 microM. AG-1478 accelerated
      the decay rate of inactivation of Kv1.5 currents without modifying the kinetics
      of current activation. Pretreatment with the structurally dissimilar PTK
      inhibitors (genistein and lavendustin A) had no effect on the AG-1478-induced
      inhibition of Kv1.5 and did not modify the AG-1478-induced current kinetics. The
      rate constants for binding and unbinding of AG-1478 were 1.46 microM(-1) x s(-1)
      and 10.19 s(-1), respectively. The AG-1478-induced inhibition of Kv1.5 channels
      was voltage dependent, with a steep increase over the voltage range of channel
      opening. However, the inhibition exhibited voltage independence over the voltage
      range in which channels are fully activated. AG-1478 produced no significant
      effect on the steady-state activation or inactivation curves. AG-1478 slowed the
      deactivation time course, resulting in a tail crossover phenomenon. Inhibition of
      Kv1.5 by AG-1478 was use dependent. The present results suggest that AG-1478 acts
      directly on Kv1.5 currents as an open-channel blocker and independently of the
      effects of AG-1478 on PTK activity.

PMID- 11997262
TI  - Cx40 and Cx43 expression ratio influences heteromeric/ heterotypic gap junction
      channel properties.
AB  - In cells that coexpress connexin (Cx)40 and Cx43, the ratio of expression can
      vary depending on the cellular environment. We examined the effect of changing
      Cx40:Cx43 expression ratio on functional gap junction properties. Rin cells
      transfected with Cx40 or Cx43 (Rin40, Rin43) were cocultured with 6B5n, A7r5,
      A7r540C1, or A7r540C3 cells for electrophysiological and dye coupling analysis.
      Cx40:Cx43 expression ratio in 6B5n, A7r5, A7r540C1, and A7r540C3 cells was ~1:1,
      3:1, 5:1, and 10:1, respectively. When Rin43 cells were paired with coexpressing
      cells, there was an increasing asymmetry of voltage-dependent gating and a shift
      toward smaller conductance events as Cx40:Cx43 ratio increased in the
      coexpressing cell. These observations could not be predicted by linear
      combinations of Cx40 and Cx43 properties in proportion to the expressed ratios of
      the two Cxs. When Rin40 cells were paired with coexpressing cells, the net
      voltage gating and single-channel conductance behavior were similar to those of
      Rin40/Rin40 cell pairs. Dye permeability properties of cell monolayers
      demonstrated that as Cx40:Cx43 expression ratio increased in coexpressing cells
      the charge and size selectivity of dye transfer reflected that of Rin40 cells, as
      would be predicted. These data indicate that the electrophysiological properties
      of heteromeric/heterotypic channels are not directly related to the proportions
      of Cx constituents expressed in the cell; however, the dye permeability of these
      same channels can be predicted by the relative Cx contributions.

PMID- 11997263
TI  - The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh
      7 cells.
AB  - ClC-3 is a voltage-gated Cl- channel that is highly conserved and widely
      expressed, although its function, localization, and properties remain a matter of
      considerable debate. In this study, we have shown that heterologous expression of
      ClC-3 in either Chinese hamster ovary (CHO-K1) or human hepatoma (Huh-7) cells
      results in the formation of large, acidic vesicular structures within cells.
      Vesicle formation is prevented by bafilomycin, an inhibitor of the vacuolar
      ATPase, and is not induced by an E224A mutant of ClC-3 with altered channel
      activity. This demonstrates that vesicle formation requires both proton pumping
      and Cl- channel activity. Manipulation of the intracellular Cl- concentration
      demonstrated that the ClC-3-associated vesicles shrink and swell consistent with
      a highly Cl--permeable membrane. The ClC-3 vesicles were identified as lysosomes
      based on their colocalization with the lysosome-associated proteins lamp-1, lamp
      2, and cathepsin D and on their failure to colocalize with fluorescently labeled
      endosomes. We conclude that ClC-3 is an intracellular channel that conducts Cl-
      when it is present in intracellular vesicles. Its overexpression results in its
      appearance in enlarged lysosome-like structures where it contributes to
      acidification by charge neutralization.

PMID- 11997264
TI  - Coordinated expression of UT-A and UT-B urea transporters in rat testis.
AB  - The blood-seminiferous tubule barrier is responsible for maintaining the unique
      microenvironment conducive to spermatogenesis. A key feature of the blood-testis
      barrier is selective permeability to solutes and water transport, conferred by
      the Sertoli cells of the seminiferous tubules (SMTs). Movement of fluid into the
      lumen of the seminiferous tubule is crucial to spermatogenesis. By Northern
      analysis, we have shown that 4.0-, 3.3-, 2.8-, and ~1.7-kb UT-A mRNA transcripts
      and a 3.8-kb UT-B mRNA transcript are detected within rat testis. Western
      analysis revealed the expression of both characterized and novel UT-A and UT-B
      proteins within the testis. Immunolocalization studies determined that UT-A and
      UT-B protein expression are coordinated with the developmental stage of the SMT.
      UT-A proteins were detected in Sertoli cell nuclei at all stages of tubule
      development and in residual bodies of stage VIII tubules. UT-B protein was
      expressed on Sertoli cell membranes of stage II-III tubules. Using in vitro
      perfusion, we determined that a phloretin-inhibitable urea pathway exists across
      the SMTs of rat testis and conclude that UT-B is likely to participate in this
      pathway.

PMID- 11997265
TI  - Regulation of the cardiac L-type Ca2+ channel by the actin-binding proteins alpha
      actinin and dystrophin.
AB  - The actin-binding proteins dystrophin and alpha-actinin are members of a family
      of actin-binding proteins that may link the cytoskeleton to membrane proteins
      such as ion channels. Previous work demonstrated that the activity of Ca2+
      channels can be regulated by agents that disrupt or stabilize the cytoskeleton.
      In the present study, we employed immunohistochemical and electrophysiological
      techniques to investigate the potential regulation of cardiac L-type Ca2+ channel
      activity by dystrophin and alpha-actinin in cardiac myocytes and in heterologous
      cells. Both actin-binding proteins were found to colocalize with the Ca2+ channel
      in mouse cardiac myocytes and to modulate channel function. Inactivation of the
      Ca2+ channel in cardiac myocytes from mice lacking dystrophin (mdx mice) was
      reduced compared with that in wild-type myocytes, voltage dependence of
      activation was shifted by 5 mV to more positive potentials, and stimulation by
      the beta-adrenergic pathway and the dihydropyridine agonist BAY K 8644 was
      increased. Furthermore, heterologous coexpression of the Ca2+ channel with
      muscle, but not nonmuscle, forms of alpha-actinin was also found to reduce
      inactivation. As might be predicted from a reduction of Ca2+ channel
      inactivation, a prolonging of the mouse electrocardiogram QT was observed in mdx
      mice. These results suggest a combined role for dystrophin and alpha-actinin in
      regulating the activity of the cardiac L-type Ca2+ channel and a potential
      mechanism for cardiac dysfunction in Duchenne and Becker muscular dystrophies.

PMID- 11997266
TI  - Reduced folate carrier transports thiamine monophosphate: an alternative route
      for thiamine delivery into mammalian cells.
AB  - Although the reduced folate carrier RFC1 and the thiamine transporters THTR-1 and
      THTR-2 share approximately 40% of their identity in protein sequence, RFC1 does
      not transport thiamine and THTR-1 and THTR-2 do not transport folates. In the
      present study, we demonstrate that transport of thiamine monophosphate (TMP), an
      important thiamine metabolite present in plasma and cerebrospinal fluid, is
      mediated by RFC1 in L1210 murine leukemia cells. Transport of TMP was augmented
      by a factor of five in cells (R16) that overexpress RFC1 and was markedly
      inhibited by methotrexate, an RFC1 substrate, but not by thiamine. At a near
      physiological concentration (50 nM), TMP influx mediated by RFC1 in wild-type
      L1210 cells was approximately 50% of thiamine influx mediated by thiamine
      transporter(s). Within 1 min, the majority of TMP transported into R16 cells was
      hydrolyzed to thiamine with a component metabolized to thiamine pyrophosphate,
      the active enzyme cofactor. These data suggest that RFC1 may be one of the
      alternative transport routes available for TMP in some tissues when THTR-1 is
      mutated in the autosomal recessive disorder thiamine-responsive megaloblastic
      anemia.

PMID- 11997268
TI  - On the reanalysis of the GISSI-Prevenzione.

PMID- 11997269
TI  - Adenylyl cyclase: a new target for heart failure therapeutics.

PMID- 11997270
TI  - Common estrogen receptor polymorphism augments effects of hormone replacement
      therapy on E-selectin but not C-reactive protein.
AB  - BACKGROUND: The estrogen receptor-alpha (ER-alpha) IVS1-401 polymorphism
      identifies a group of women (approximately 20%) who have augmented effects of
      hormone replacement therapy (HRT) on levels of HDL cholesterol. This study sought
      to determine if this augmentation extends to HRT regulation of E-selectin and C
      reactive protein (CRP) and to explore possible mechanisms by which this
      polymorphism might influence estrogen action. METHODS AND RESULTS: Serum levels
      of soluble E-selectin and CRP were measured at baseline and 1 year in 264
      postmenopausal women randomized to treatment with oral conjugated equine estrogen
      (0.625 mg/d), estrogen plus progestin (medroxyprogesterone acetate 2.5 mg/d), or
      placebo. Women with the ER-alpha IVS1-401 C/C genotype receiving HRT had nearly a
      2-fold greater reduction in E-selectin compared with C/T or T/T women (P for
      interaction=0.02). In contrast, there was no augmentation of the HRT-associated
      increase in CRP among the C/C women compared with C/T or T/T women (P for
      interaction=0.54). Of luciferase reporter constructs containing sequences
      spanning the IVS1-401 T/C polymorphism, expression of the construct containing
      the C allele was enhanced >10-fold, with cotransfection of a constitutively
      expressed B-myb vector. In contrast, B-myb resulted in only a 2.5-fold increase
      in expression of the T allele construct. CONCLUSIONS: Women with the ER-alpha
      IVS1-401 C/C genotype have greater reductions in E-selectin but no further
      increases in CRP with HRT. The C allele produces a functional binding site for
      the transcription factor B-myb. The impact of this polymorphism on ER-alpha
      transcription and other estrogen-sensitive intermediate and clinical end points
      has not yet been established.

PMID- 11997271
TI  - First clinical experience with a paclitaxel derivate-eluting polymer stent system
      implantation for in-stent restenosis: immediate and long-term clinical and
      angiographic outcome.
AB  - BACKGROUND: It has been shown that antiproliferative drugs such as paclitaxel
      lower the amount of intimal hyperplasia after stent implantation. We report the
      first clinical experience of 7-hexanoyltaxol (QP2)-eluting polymer stent system
      (QuaDS) implantation for in-stent restenosis. METHODS AND RESULTS: Fifteen
      consecutive patients with elective indication to percutaneous coronary
      intervention for in-stent restenosis were treated with the QuaDS-QP2 stent
      implantation. The QuaDS-QP2 stent was successfully implanted in all but 2 target
      lesions. In one lesion, the restenotic segment could not be completely covered by
      the stent, and in another lesion, a bare metal stent was implanted distally to
      the QuaDS-QP2 stent. One patient suffered from postprocedural non-Q-wave
      myocardial infarction (NQWMI). No other adverse events were observed during
      hospital stay. Six- and 12-month angiographic and clinical follow-up was
      scheduled for all patients. At 6 months, 3 patients had target lesion
      revascularization (20%). Two patients had restenosis (13.3%); one experienced
      restenosis in a gap between 2 drug-eluting stents, and the other had stent
      occlusion leading to NQWMI. Minimal intimal hyperplasia was observed in all the
      segments covered by drug-eluting stents (late loss=0.47+/-1.01 mm with a loss
      index=0.17+/-0.39). At 12 months, 1 patient suffered from NQWMI, and 8 of 13
      patients (61.5%) had angiographic restenosis (late loss=1.36+/-0.94 mm with a
      loss index=0.62+/-0.44). CONCLUSION: This first experience with QuaDS-QP2 stent
      implantation for in-stent restenosis revealed minimal intimal hyperplasia at the
      6-month follow-up. However, the antiproliferative effect was not maintained at
      the 12-month follow-up, resulting in delayed occurrence of angiographic
      restenosis.

PMID- 11997272
TI  - Percutaneous left atrial appendage transcatheter occlusion to prevent stroke in
      high-risk patients with atrial fibrillation: early clinical experience.
AB  - BACKGROUND: Thromboembolism due to atrial fibrillation (AF) is a frequent cause
      of stroke. More than 90% of thrombi in AF form in the left atrial appendage
      (LAA). Obliteration of the appendage may prevent embolic complications. METHODS
      AND RESULTS: We evaluated the feasibility and safety of implanting a novel device
      for percutaneous left atrial appendage transcatheter occlusion (PLAATO). LAA
      occlusion using the PLAATO system was attempted in 15 patients with chronic AF at
      high risk for stroke, who are poor candidates for long-term warfarin therapy. The
      implant consists of a self-expanding nitinol cage covered with a polymeric
      membrane (ePTFE). The LAA was successfully occluded in 15/15 patients (100%).
      Angiography and transesophageal echocardiography (TEE) during the procedure
      showed that the device was well-seated in all patients and that there was no
      evidence of perforation, device embolization, or interference with surrounding
      structures. In 1 patient, the first procedure was complicated by a
      hemopericardium, which occurred during LAA access. A second attempt 30 days later
      was successful with no untoward sequela. No other complications occurred. At 1
      month follow-up, chest fluoroscopy and TEE revealed continued stable implant
      position with smooth atrial-facing surface and no evidence of thrombus.
      CONCLUSIONS: Thus, transcatheter closure of the LAA is feasible in humans. This
      novel implant technology may be appropriate for patients with AF who are not
      suitable candidates for anticoagulation therapy. Further trials are needed to
      show the long-term safety and its efficacy in reducing stroke.

PMID- 11997273
TI  - Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic
      effects of C-reactive protein.
AB  - BACKGROUND: C-reactive protein (CRP) has been suggested to actively participate
      in the development of atherosclerosis. In the present study, we examined the role
      of the potent endothelium-derived vasoactive factor endothelin-1 (ET-1) and the
      inflammatory cytokine interleukin-6 (IL-6) as mediators of CRP-induced
      proatherogenic processes. METHODS AND RESULTS: Saphenous vein endothelial cells
      (HSVECs) were incubated with human recombinant CRP (25 microg/mL, 24 hours) and
      the expression of vascular cell adhesion molecule (VCAM-1), intracellular
      adhesion molecule (ICAM-1), and monocyte chemoattractant chemokine-1 was
      determined. The effects of CRP on LDL uptake were assessed in macrophages using
      immunofluorescent labeling of CD32 and CD14. In each study, the effect of
      endothelin antagonism (bosentan) and IL-6 inhibition (monoclonal anti-IL-6
      antibodies) was examined. The effects of CRP on the secretion of ET-1 and IL-6
      from HSVECs were also evaluated. Incubation of HSVECs with recombinant human CRP
      resulted in a marked increase in ICAM-1 and VCAM-1 expression (P<0.001).
      Likewise, CRP caused a significant increase in monocyte chemoattractant chemokine
      1 production, a key mediator of leukocyte transmigration (P<0.001). CRP caused a
      marked and sustained increase in native LDL uptake by macrophages (P<0.05). These
      proatherosclerotic effects of CRP were mediated, in part, via increased secretion
      of ET-1 and IL-6 (P<0.01) and were attenuated by both bosentan and IL-6
      antagonism (P<0.01). CONCLUSIONS: CRP actively promotes a proatherosclerotic and
      proinflammatory phenotype. These effects are mediated, in part, via the
      production of ET-1 and IL-6 and are attenuated by mixed ET(A/B) receptor
      antagonism and IL-6 inhibition. Bosentan may be useful in decreasing CRP-mediated
      vascular disease.

PMID- 11997274
TI  - Early protection against sudden death by n-3 polyunsaturated fatty acids after
      myocardial infarction: time-course analysis of the results of the Gruppo Italiano
      per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.
AB  - BACKGROUND: Our purpose was to assess the time course of the benefit of n-3
      polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI
      Prevenzione trial in patients surviving a recent (<3 months) myocardial
      infarction. METHODS AND RESULTS: In this study, 11 323 patients were randomly
      assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment
      (control) on top of optimal pharmacological treatment and lifestyle advice.
      Intention-to-treat analysis adjusted for interaction between treatments was
      carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular,
      cardiac, coronary, and sudden death; nonfatal myocardial infarction; total
      coronary heart disease; and cerebrovascular events was assessed by right
      censoring follow-up data 12 times from the first month after randomization up to
      12 months. Survival curves for n-3 PUFA treatment diverged early after
      randomization, and total mortality was significantly lowered after 3 months of
      treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction
      in risk of sudden death was specifically relevant and statistically significant
      already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly
      significant, although delayed, pattern after 6 to 8 months of treatment was
      observed for cardiovascular, cardiac, and coronary deaths. CONCLUSIONS: The early
      effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports
      the hypothesis of an antiarrhythmic effect of this drug. Such a result is
      consistent with the wealth of evidence coming from laboratory experiments on
      isolated myocytes, animal models, and epidemiological and clinical studies.

PMID- 11997275
TI  - Familial aggregation of blood lipid response to exercise training in the health,
      risk factors, exercise training, and genetics (HERITAGE) Family Study.
AB  - BACKGROUND: Fasting levels of plasma lipids and lipoproteins are reported to
      improve with regular exercise training. However, little is known on whether the
      training responses are influenced by heritable factors. METHODS AND RESULTS: The
      lipid profile was assessed in 115 black (224 individuals) and 99 white families
      (469 individuals), who participated in the HERITAGE Family Study, while in a
      sedentary state (baseline visit) and after exercise training for 20 weeks (post
      visit). Variables included total cholesterol, triglyceride, low-density
      lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), high-density
      lipoprotein cholesterol (HDL-C), apolipoprotein A-I, and HDL-C subfractions 2
      (HDL2-C) and 3 (HDL3-C). Familial correlations for the training responses
      (Delta=post-baseline) were significant for most variables, and the percent
      variance accounted for by familial factors (ie, maximal heritabilities) ranged
      from 25% to 38%. Exceptions were for higher heritabilities near 60% for DeltaApoB
      in blacks and DeltaHDL2-C in whites and a lower estimate of zero for DeltaLDL-C
      in blacks. CONCLUSIONS: Heritable factors in part determine lipid profile
      responses to regular exercise. Maximal heritabilities were similar across ethnic
      groups and variables, except for DeltaLDL-C, DeltaApoB, and DeltaHDL2-C.
      Molecular studies to identify the markers and genes associated with these
      influences are currently underway.

PMID- 11997276
TI  - Relationship of the TIMI myocardial perfusion grades, flow grades, frame count,
      and percutaneous coronary intervention to long-term outcomes after thrombolytic
      administration in acute myocardial infarction.
AB  - BACKGROUND: Although 90-minute TIMI flow grades (TFGs), corrected TIMI frame
      counts (CTFCs), and TIMI myocardial perfusion grades (TMPGs) have been associated
      with 30-day outcomes, we hypothesized that these indices would be related to long
      term outcomes after thrombolytic administration. METHODS AND RESULTS: As a
      substudy of the TIMI 10B trial (tissue plasminogen activator versus
      tenecteplase), 49 centers carried out 2-year follow-up. TIMI grade 2/3 flow (Cox
      hazard ratio [HR] 0.41, P=0.001), reduced CTFCs (faster flow, P=0.02), and an
      open microvasculature (TMPG 2/3) (HR 0.51, P=0.038) were all associated with
      improved 2-year survival. Rescue percutaneous coronary intervention (PCI) of
      closed arteries (TFG 0/1) at 90 minutes was associated with reduced mortality
      (P=0.03), and mortality trended lower with adjunctive PCI of open (TFG 2/3)
      arteries (P=0.11). In a multivariate model correcting for previously identified
      correlates of mortality (age, sex, pulse, left anterior descending coronary
      artery infarction, and any PCI during initial hospitalization), patency (TFG 2/3)
      (HR 0.32, P<0.001), CTFC (P=0.01), and TMPG 2/3 remained associated with reduced
      mortality (HR 0.46, P=0.02). CONCLUSIONS: Both improved epicardial flow (TFG 2/3
      and low CTFCs) and tissue-level perfusion (TMPG 2/3) at 90 minutes after
      thrombolytic administration are independently associated with improved 2-year
      survival, suggesting complementary mechanisms of improved long-term survival.
      Although rescue PCI reduced long-term mortality, improved microvascular perfusion
      (TMPG 2/3) before PCI was also related to improved mortality independently of
      epicardial blood flow and the performance of rescue or adjunctive PCI. Further
      prospective trials are warranted to re-examine the benefit of early PCI with
      thrombolysis.

PMID- 11997277
TI  - Differential influence of diabetes mellitus on increased jeopardized myocardium
      after initial angioplasty or bypass surgery: bypass angioplasty revascularization
      investigation.
AB  - BACKGROUND: Data are absent that compare midterm angiographic outcome between
      patients with and without diabetes after initial percutaneous transluminal
      coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG).
      Importantly, diabetes mellitus may differentially influence long-term survival
      after PTCA or CABG. METHODS AND RESULTS: Patients with multivessel coronary
      disease who were previously enrolled in the Bypass Angiopathy Revascularization
      Investigation to compare initial PTCA versus CABG (n=1829) and who had a
      reduction in jeopardized myocardium after initial revascularization and at least
      1 angiogram during 5-year follow-up were analyzed (n=897). This included 369 CABG
      treated patients (16% with diabetes) and 528 PTCA-treated patients (18% with
      diabetes). The influence of diabetes on angiographic increase in percentage of
      jeopardized myocardium after initial revascularization with either PTCA or CABG
      was investigated. Among PTCA patients, the mean percentage increase in total
      jeopardized myocardium was significantly greater in those with diabetes than in
      those without at 1-year protocol-directed angiography (42% versus 24%, P=0.05)
      and on the first clinically performed (unscheduled) angiogram within 30 months
      (63% versus 50%, P=0.01) but not at 5-year protocol-directed angiography (34%
      versus 26%, P=0.33). This excess midterm risk associated with diabetes persisted
      after statistical adjustment. In contrast, among CABG patients, diabetes was not
      associated with percentage increase in jeopardized myocardium at any angiographic
      follow-up interval. CONCLUSIONS: Presence of diabetes differentially influences
      worsening of jeopardized myocardium after initial PTCA compared with CABG. This
      differential effect occurs irrespective of whether follow-up angiography is
      undertaken for clinical or nonclinical purposes.

PMID- 11997278
TI  - Angiotensinogen genotype affects renal and adrenal responses to angiotensin II in
      essential hypertension.
AB  - BACKGROUND: Renovascular and adrenal responses to infused angiotensin II (Ang II)
      are intermediate phenotypes that may indirectly reflect tissue renin-angiotensin
      system activity. We examine herein angiotensinogen (AGT) as a candidate gene to
      help elucidate potential mechanisms for previously reported AGT linkage and
      association studies. METHODS AND RESULTS: Renal plasma flow and plasma
      aldosterone were measured before and after a 45-minute infusion of Ang II (3 ng x
      kg(-1) x min(-1)) in 190 hypertensive patients who were on carefully controlled
      high- and low-salt diets. Reduced renal vascular (P=0.0002) and adrenal (P=0.002)
      responses to infused exogenous Ang II were associated with the AGT -6A allele. In
      multiple logistic regression, greater body mass index, lower basal renal plasma
      flow, and higher diastolic blood pressure together with AGT -6A genotype were
      associated with lower renal vascular response. In contrast, only male sex and AGT
      -6A genotype were associated with lower adrenal response. When both the renal and
      adrenal responses to Ang II were in the lowest tertile, the AGT -6AA genotype was
      present in 55.6%; in contrast, when both responses were in the upper 2 tertiles,
      the -6AA genotype was present in only 17.8% (P=0.001). CONCLUSIONS: A clear
      association between AGT genotype and response to infused Ang II was demonstrated
      for both the renal vasculature and the adrenal, consistent with the hypothesis
      that the AGT -6A genotype results in increased tissue expression of
      angiotensinogen and Ang II.

PMID- 11997279
TI  - Mitral ratio of peak early to late diastolic filling velocity as a predictor of
      mortality in middle-aged and elderly adults: the Strong Heart Study.
AB  - BACKGROUND: With aging, left ventricular filling tends to decrease in early
      diastole, reducing the mitral ratio of peak early to late diastolic filling
      velocity (E/A). However, the prognostic significance of low or high E/A in older
      adults remains to be elucidated in population-based samples. METHODS AND RESULTS:
      Doppler echocardiograms were analyzed in 3008 American Indian participants in the
      second Strong Heart Study examination who had no more than mild mitral or aortic
      regurgitation. Participants were followed for a mean of 3 years after Doppler
      echocardiography to assess risks of all-cause and cardiac death associated with
      E/A <0.6 or >1.5; 2429 (81%) participants had normal E/A ratio, 490 (16%) had E/A
      <0.6, and 89 (3%) had E/A >1.5. All-cause mortality was higher with E/A <0.6 or
      E/A >1.5 (12% and 13% versus 6%), as was cardiac mortality (4.5% and 6.5% versus
      1.6%; both P<0.001). Adjusting for age, sex, body mass index, systolic blood
      pressure, HDL and LDL cholesterol, smoking, hypertension, diabetes, coronary
      heart disease, left ventricular hypertrophy, and low ejection fraction (<40%),
      the relative risk of all-cause death with E/A >1.5 was 1.73 (95% CI, 0.99 to
      3.03; P=0.05); the relative risk of cardiac death was 2.8 (95% CI, 1.19 to 6.75;
      P<0.05). E/A <0.6 was not independently associated with increased all-cause or
      cardiac mortality (P=0.19 and 0.31, respectively) after adjusting for covariates.
      CONCLUSIONS: In a population-based sample of middle-aged and elderly adults,
      mitral E/A >1.5 at baseline Doppler echocardiography is associated with 2-fold
      increased all-cause and 3-fold increased cardiac mortality independent of
      covariates; mitral E/A <0.6 was also associated with 2-fold increased all-cause
      and cardiac mortality but not independent of covariates.

PMID- 11997280
TI  - Characterization of reentrant circuits in left atrial macroreentrant tachycardia:
      critical isthmus block can prevent atrial tachycardia recurrence.
AB  - BACKGROUND: Left atrial macroreentrant tachycardia (LAMRT) has not been
      characterized in detail. METHODS AND RESULTS: Twenty-eight patients with LAMRT,
      including 4 patients with ablated typical atrial flutter (AFL), underwent
      electroanatomic mapping of the left atrium (LA) between February 1999 and October
      2001. LA maps were performed during LAMRT in 26 patients and during sinus rhythm
      in 2 patients. Electrically silent areas or continuous lines of double potentials
      were identified as acquired anatomic barriers in all patients. In 23 of 26
      patients with LAMRT mapping, 42 reentry circuits with a protected isthmus were
      identified. The isthmus was 11.8+/-5.9 mm wide, with the maximal amplitude of
      0.07 to 3.61 mV. Radiofrequency pulses terminated all LAMRTs in 23 patients and
      resulted in conduction block across the isthmus in 20 patients. In 2 patients
      with sinus mapping, all identified isthmuses were ablated. Additionally, AFL was
      induced and ablated in 6 patients. Atrial tachycardia recurred in 4 patients: 3
      patients without validated block across the isthmus presented with recurrence of
      the same LAMRT, and 1 patient without ablated cavotricuspid isthmus presented
      with AFL. All tachycardias were abolished during a second procedure. Of 25
      patients with identified isthmuses, 20 patients were without atrial arrhythmia
      and 5 had only atrial fibrillation during a median follow-up of 14 months.
      CONCLUSION: The reentry circuit with a protected isthmus can be identified in 89%
      patients with LAMRT by electroanatomic mapping. The isthmuses were amenable to
      radiofrequency applications in most patients. No atrial tachycardia recurred in
      any patients with isthmus block.

PMID- 11997281
TI  - Allelic variants in long-QT disease genes in patients with drug-associated
      torsades de pointes.
AB  - BACKGROUND: DNA variants appearing to predispose to drug-associated "acquired"
      long-QT syndrome (aLQTS) have been reported in congenital long-QT disease genes.
      However, the incidence of these genetic risk factors has not been systematically
      evaluated in a large set of patients with aLQTS. We have previously identified
      functionally important DNA variants in genes encoding K+ channel ancillary
      subunits in 11% of an aLQTS cohort. METHODS AND RESULTS: The coding regions of
      the genes encoding the pore-forming channel proteins KvLQT1, HERG, and SCN5A were
      screened in (1) the same aLQTS cohort (n=92) and (2) controls, drawn from
      patients tolerating QT-prolonging drugs (n=67) and cross sections of the Middle
      Tennessee (n=71) and US populations (n=90). The frequency of three common
      nonsynonymous coding region polymorphisms was no different between aLQTS and
      control subjects, as follows: 24% versus 19% for H558R (SCN5A), 3% versus 3% for
      R34C (SCN5A), and 14% versus 14% for K897T (HERG). Missense mutations (absent in
      controls) were identified in 5 of 92 patients. KvLQT1 and HERG mutations (one
      each) reduced K+ currents in vitro, consistent with the idea that they augment
      risk for aLQTS. However, three SCN5A variants did not alter I(Na), which argues
      that they played no role in the aLQTS phenotype. CONCLUSIONS: DNA variants in the
      coding regions of congenital long-QT disease genes predisposing to aLQTS can be
      identified in approximately 10% to 15% of affected subjects, predominantly in
      genes encoding ancillary subunits.

PMID- 11997282
TI  - Human leukocyte antigen-G expression after heart transplantation is associated
      with a reduced incidence of rejection.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-G, a nonclassic major
      histocompatibility complex class I molecule expressed in the extravillous
      cytotrophoblast at the feto-maternal interface, is known to protect the fetus
      from maternal cellular immunity. In a preliminary study, we showed that HLA-G is
      expressed in the hearts of some patients after heart transplantation. METHODS AND
      RESULTS: In the present study, a larger number of patients was investigated to
      confirm this finding and to look for possible correlations between HLA-G
      expression and the number and types of rejection. Expression of HLA-G in
      endomyocardial biopsy specimens was investigated by immunohistochemical analysis,
      and detection of the soluble HLA-G in the serum was performed by
      immunoprecipitation followed by Western blot analysis. HLA-G was detected in the
      biopsy specimens and serum of 9 of 51 patients (18%). The number of episodes of
      acute rejection was significantly lower in HLA-G-positive patients (1.2+/-1.1) as
      compared with HLA-G-negative patients (4.5+/-2.8) (P<0.001). No chronic rejection
      was observed in HLA-G-positive patients, whereas 15 HLA-G-negative patients had
      chronic rejection (P<0.032). A longitudinal study of these patients reveals that
      the status of HLA-G expression was maintained after 6 months both in serum and in
      biopsy specimens. During this period, HLA-G-positive patients did not have
      chronic rejection. CONCLUSIONS: There is a significant correlation between
      rejection and HLA-G expression in the heart after transplantation. HLA-G
      expression and its effect in reducing the incidence and severity of rejection
      seem to be stable throughout the evolution.

PMID- 11997283
TI  - Myocardial ischemic injury after heart transplantation is associated with
      upregulation of vitronectin receptor (alpha(v)beta3), activation of the matrix
      metalloproteinase induction system, and subsequent development of coronary
      vasculopathy.
AB  - BACKGROUND: Myocardial ischemic injury after heart transplantation is associated
      with subsequent development of graft vasculopathy. Both vitronectin receptor
      (integrin alpha(v)beta3) and tissue factor play key roles in vascular endothelial
      cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury
      models. METHODS AND RESULTS: Thirteen patients developed myocardial ischemic
      injury within 2 weeks of cardiac transplantation (ischemia group). These were
      compared with 10 transplantation patients who had no evidence of ischemia
      (control group). Endomyocardial biopsies were evaluated within 2 weeks of
      transplantation for alpha(v)beta3, tissue factor, and extracellular MMP inducer
      (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis
      was quantified. All patients underwent intravascular ultrasound at 1 month and 1
      year after transplantation. Compared with control, the ischemia group
      demonstrated evidence of significant increased expression of alpha(v)beta3 (3.2
      fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold,
      P=0.01). At 1 year, the ischemia group had a significant increase in myocardial
      fibrosis (24+/-1.8% versus 14+/-1.1%, P<0.001) and zymographic activity of MMP-2
      (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01).
      Coronary vasculopathy progression was also more advanced in the ischemia group
      (change in coronary maximal intimal thickness over 1 year 0.54+/-0.1 versus
      0.26+/-0.06 mm; P=0.031). CONCLUSIONS: Myocardial ischemic injury after cardiac
      transplantation is associated with upregulation of alpha(v)beta3, tissue factor,
      and activation of the MMP induction system, which may contribute to the
      subsequent development of allograft remodeling and vasculopathy.

PMID- 11997284
TI  - Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin synthase gene
      transfer protect against ischemic cerebral infarction.
AB  - BACKGROUND: We tested the hypothesis that bicistronic cyclooxygenase-1 (COX
      1)/prostacyclin synthase (PGIS) and COX-1 gene transfer reduce cerebral infarct
      volume by augmenting synthesis of protective prostaglandins. METHODS AND RESULTS:
      We infused into lateral ventricle of a rat stroke model recombinant adenoviruses
      (rAd) containing COX-1 (Adv-COX-1), COX-1 and PGIS (Adv-COX-1/PGIS), or Adv-PGK
      control vector, and we determined COX-1 and PGIS protein and eicosanoid levels
      and infarct volume. COX-1 and PGIS proteins were increased in a time-dependent
      manner. Adv-COX-1/PGIS infusion selectively augmented prostacyclin levels, with
      reduction of other eicosanoids in ischemic cortex and a significant reduction of
      infarct volume, even when the rAd was administered 5 hours after ischemia.
      Infusion of Adv-COX-1 also increased prostacyclin, suppressed leukotriene levels,
      and achieved a similar degree of cerebral protection. Its neuroprotection was
      abrogated by treatment with a selective COX-1 inhibitor. CONCLUSIONS: COX-1/PGIS
      and COX-1 gene transfer reduce cerebral infarct volume by augmenting prostacyclin
      and suppressing leukotriene productions. COX-1-based gene transfer has potential
      for treating ischemic stroke.

PMID- 11997285
TI  - Comparative antithrombotic effects of magnesium sulfate and the platelet
      glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide in a canine model of
      stent thrombosis.
AB  - BACKGROUND: Antithrombotic effects of glycoprotein IIb/IIIa inhibitors and
      magnesium are known, but their comparative effects on stent thrombosis are not
      known. Our objective was to compare the antithrombotic effects of the
      glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide with magnesium in an
      ex vivo canine arteriovenous shunt model of stent thrombosis. METHODS AND
      RESULTS: Control nitinol stents were expanded to 2 mm in diameter in a tubular
      perfusion chamber interposed in the shunt and exposed to flowing arterial blood
      at a shear rate of 2100 s(-1) for 20 minutes (n=398 perfusion runs in 24
      experiments in 8 dogs). The animals were treated intravenously with MgSO4 (2 g
      bolus x 20 minutes followed by 2 g/h infusion), eptifibatide (double bolus of 180
      microg/kg 10 minutes apart followed by 2 microg/kg per minute), or tirofiban (0.3
      microg/kg per minute), with or without heparin (50 U/kg). Effects of the test
      agents on thrombus weight, platelet aggregation (PA), platelet CD62 expression,
      bleeding time (BT), heart rate, and mean arterial blood pressure were assessed.
      Treatment with Mg+heparin reduced stent thrombus weight by 78+/-10% compared with
      baseline (19+/-4 mg, P<0.001). The antithrombotic effect of Mg+heparin was
      equivalent to that observed with tirofiban+heparin (78+/-13%) and
      eptifibatide+heparin (84+/-11%). Magnesium had no significant effect on PA and
      BT. Tirofiban and eptifibatide inhibited PA by >90% and prolonged BT up to 20
      minutes. None of the test agents had effects on CD62 expression or activated
      clotting time. There were no significant bleeding or hemodynamic complications.
      CONCLUSION: Magnesium produced a significant reduction in acute stent thrombus
      formation that was equivalent in magnitude to that produced by clinically
      relevant doses of tirofiban and eptifibatide. Its potential use in percutaneous
      coronary intervention requires further study.

PMID- 11997286
TI  - Foam cell formation inhibits growth of Chlamydia pneumoniae but does not
      attenuate Chlamydia pneumoniae-induced secretion of proinflammatory cytokines.
AB  - BACKGROUND: It has not yet been determined whether lipid-loaded macrophages (foam
      cells), a major cellular component of atherosclerotic lesions, have the capacity
      to support growth of Chlamydia pneumoniae and be activated to secrete
      proinflammatory cytokines in response to C pneumoniae infection. METHODS AND
      RESULTS: Lipid loading of RAW 264.7 cells and mouse peritoneal macrophages with
      either oxidized or acetylated LDL significantly inhibits the growth of C
      pneumoniae. Modified forms of LDL are not directly toxic to C pneumoniae and do
      not inhibit either the initial binding or internalization of C pneumoniae by
      macrophages. Lipid loading does not reduce infection of macrophages with
      Chlamydia trachomatis. Treatment of lipid-loaded macrophages with live, heat
      killed, or UV-inactivated C pneumoniae stimulates secretion of cytokines. C
      pneumoniae also induces expression of the mRNA for tumor necrosis factor-alpha in
      foam cells despite inhibition of nuclear factor-kappaB binding to DNA by prior
      treatment with oxidized LDL. CONCLUSIONS: Foam cell formation is not conducive to
      growth of C pneumoniae but does not inhibit the C pneumoniae-induced secretion of
      proinflammatory cytokines.

PMID- 11997287
TI  - Effects of matrix metalloproteinase inhibition on ventricular remodeling due to
      volume overload.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy and dilatation are important
      compensatory responses to chronic volume overload. Although LV function is
      initially preserved by these responses, the continued structural remodeling of
      the myocardium ultimately becomes maladaptive, leading to the development of
      heart failure. We have shown previously that increased myocardial matrix
      metalloproteinase (MMP) activity precedes LV dilatation induced by a chronic
      volume overload. Accordingly, this study focused on the effects of MMP inhibition
      therapy (PD 166793, 1 mg x kg(-1) x d(-1)) on LV size and function in a rat model
      of volume overload-induced heart failure. METHODS AND RESULTS: Rats were divided
      into the following groups: treated and untreated infrarenal abdominal aortocaval
      fistula and treated and untreated sham-operated (control). LV weights of both
      fistula groups were increased above that of the control group (868+/-79 mg; P< or
      =0.001); LV weights in the treated fistula group, however, were lower than in the
      untreated fistula group at 8 weeks (1447+/-186 versus 1715+/-279 mg,
      respectively; P< or =0.012). The marked ventricular dilatation seen in the
      untreated fistula group was significantly diminished in the treated fistula
      group, although the increase in LV compliance was similar in both treated and
      untreated fistula hearts. CONCLUSIONS: MMP inhibition significantly attenuates
      the myocardial remodeling associated with chronic volume overload, as evidenced
      by prevention of dilatation, a marked reduction in LV hypertrophy, and
      preservation of ventricular function.

PMID- 11997288
TI  - Adenylyl cyclase increases survival in cardiomyopathy.
AB  - BACKGROUND: To test the hypothesis that increased cardiac adenylyl cyclase type
      VI (AC(VI)) content, which results in increased cAMP generation, would increase
      survival in cardiomyopathy, we crossbred mice with Gq-associated cardiomyopathy
      and those with cardiac-directed expression of AC(VI). We also assessed myocardial
      hypertrophy after prolonged cardiac expression of Gq versus coexpression of Gq
      and AC(VI). METHODS AND RESULTS: Three experimental groups, Gq/AC (double
      positive), Gq, and control (double negative), were studied. Survival was
      increased by cardiac-directed expression of AC(VI) (P<0.0001), and Gq/AC mice had
      survival rates indistinguishable from control mice. Myocardial hypertrophy
      developed in older Gq mice but was abrogated by cardiac expression of AC(VI), as
      documented by the ratio of ventricular weight to tibial length (Gq, 11.93+/-0.99
      mg/mm, n=11; Gq/AC, 8.00+/-0.73 mg/mm, n=9; P<0.01) and by left ventricular
      cardiac myocyte size (Gq, 2800+/-254 microm2, n=4; Gq/AC, 1721+/-166 microm2,
      n=5; P<0.01). Hearts of Gq mice were dilated, and function was impaired.
      Concurrent expression of AC reduced end-diastolic diameter (Gq, 4.20+/-0.15 mm,
      n=12; Gq/AC, 3.68+/-0.12 mm, n=7; P<0.05) and increased fractional shortening
      (Gq, 32+/-1%, n=12; Gq/AC, 41+/-2%, n=7; P<0.001). Cardiac myocytes from Gq/AC
      mice showed increased forskolin-stimulated cAMP production (Gq, 3.8+/-1.3
      fmol/cell, n=5; Gq/AC, 10.7+/-2.6 fmol/cell, n=6; P<0.02), documenting increased
      AC function. CONCLUSIONS: Cardiac-directed expression of AC(VI) restores myocyte
      AC function, improves heart function, increases cAMP generation, abrogates
      myocardial hypertrophy, and increases survival in Gq cardiomyopathy.

PMID- 11997289
TI  - Endovascular aneurysm repair: Magnetic resonance monitoring of histological
      organization processes in the excluded aneurysm.
AB  - BACKGROUND: The purpose of the present study was to systematically analyze the
      histopathologic organization processes in excluded aneurysms after endovascular
      stenting and to develop a noninvasive monitoring method for these processes using
      MRI. METHODS AND RESULTS: In 36 mongrel dogs, autologous aortic aneurysms were
      created. Endovascular treatment was performed using covered stents. Follow-up was
      after 1 week, 6 weeks, and 6 months. MRI was performed with T2-weighted turbo
      spin-echo sequences and T1-weighted spin-echo sequences and was repeated after
      contrast bolus with gadolinium. Histopathologic findings were correlated to
      signal intensities (SIs) of MRI images. SIs of distinct areas were analyzed and
      related to the SI of the reference tissue (SI ratio). The histological
      organization process was gradated in the following 4 classes: class 0, detritus
      without organization; classes I and II, connective tissue proliferation with
      increasing fiber synthesis; and class III, dense fibrous connective tissue. The
      SI ratios of T2-weighted images were significantly reduced from 4.76 in detritus
      (0) to 1.70 in dense fibrous connective tissue (III) as a function of
      histopathologic classes. SI ratios of T1-weighted images were reduced from 1.84
      (0) to 1.12 (III). Contrast bolus with gadolinium-DTPA showed no change of SI
      ratio in detritus (0.99) but an increase from 1.12 (I) to 1.70 (III) as
      organization increased. CONCLUSIONS: The histological organization of excluded
      aneurysms can be monitored by MRI. Progressive organization is indicated by
      decreasing SIs in T2- and an increasing signal increase in T1-weighted images
      after gadolinium bolus.

PMID- 11997290
TI  - A new paradigm for plaque stabilization.
AB  - The concept of plaque stabilization was developed to explain how lipid lowering
      could decrease adverse coronary events without a substantial reduction in the
      regression of atherosclerosis. Plaques were stabilized by reducing serum
      cholesterol leading to several favorable pathobiological changes in the vessel
      wall of lipid-rich plaques responsible for a majority of acute coronary events.
      However, this concept is limited for several reasons including that it does not
      incorporate strategies directed against either plaques that have already
      destabilized or non-lipid-rich plaques, which are the substrate for at least one
      third of major coronary thrombi and may or may not be stabilized by lipid
      lowering. For the destabilized plaque with overlying thrombus, either
      percutaneous intervention, long-term antithrombotic and/or anticoagulant therapy,
      or possibly aggressive lipid lowering stabilizes lesions by reducing subsequent
      thrombosis at the lesion site and, at least with lipid lowering, by improving
      endothelial function and possibly reducing inflammation. Short-term, in-hospital
      antithrombotic approaches alone with agents like the GP platelet IIb/IIIa
      inhibitors have not been effective in this situation. For other plaques not
      presently destabilized, the main goal of therapy is reducing future acute
      coronary events. Several classes of drugs, including ACE inhibitors, beta
      blockers, and antithrombotic agents in addition to lipid-lowering agents, reduce
      events, and this may be attributable, at least in part, to plaque-stabilizing
      effects.

PMID- 11997291
TI  - Images in cardiovascular medicine. Multislice spiral computed tomography for in
      stent restenosis.

PMID- 11997292
TI  - Images in cardiovascular medicine. Formation of a free floating left atrial
      thrombus despite three weeks of anticoagulation.

PMID- 11997294
TI  - Losartan potassium (Cozaar).

PMID- 11997295
TI  - Pulmonary defences to acute respiratory infection.
AB  - Of all sites in the body, the lung is perhaps challenged by the greatest
      onslaught of microbial pathogens, many of which would cause lethal infections if
      unopposed. The immune response to respiratory infection must, therefore, be rapid
      and efficient. However, the respiratory tract is a fragile tissue with
      architecture that is finely designed for gas exchange, so that the price of
      excessive or inappropriate inflammatory responses may itself be very high. The
      first line of defence comes from barriers such as mucus and cilia, followed by a
      battery of mediators that constitute the innate response. These include
      lactoferrin, lysozyme, collectins and defensins. Activation of these molecules
      can lead directly to lysis of pathogens, or to destruction through opsonisation
      or the recruitment of inflammatory cells. The adaptive immune response includes
      the production of neutralising antibodies and the responses of T lymphocytes.
      Different populations of T lymphocytes may dramatically alter the balance between
      clearance of the pathogen and induction of tissue damage depending on the
      cytokines they secrete.

PMID- 11997296
TI  - The pathogenesis of respiratory syncytial virus disease in childhood.
AB  - Respiratory syncytial virus (RSV) is a leading cause of severe respiratory
      infection in infants and children. RSV is an RNA virus whose genome encodes 10
      proteins. The G protein is responsible for viral attachment to cells whilst the F
      protein promotes syncytia formation. These proteins are also important in the
      immune response to RSV. Both the innate and adaptive arms of the cellular immune
      system are involved in the immunological response to RSV. The cytopathic effects
      of the virus explain many of the pathological findings in RSV disease. However,
      there is compelling evidence to suggest that the host cell immune response also
      has a prominent role in disease pathogenesis. Non-immunological factors may also
      be important.

PMID- 11997297
TI  - Viruses in asthma.
AB  - Current evidence suggests that the overall load of infectious agents, including
      respiratory viruses, encountered early in life is an important factor influencing
      maturation of the immune system from a type 2 bias at birth towards predominantly
      type 1 responses, thus avoiding atopic diseases. The 'hygiene hypothesis'
      proposes that the relatively sterile environment present in industrialised
      Western countries has contributed to the recent epidemic of asthma and atopy.
      Whether specific infections are of greater or lesser protective value is an
      important question if strategies are to be derived to mimic the beneficial
      effects of childhood infection whilst avoiding morbidity and potential mortality
      of the natural pathogens. Infection by respiratory viruses is a major trigger of
      wheezing in infants and of exacerbations of asthma in older children. Viruses are
      detected in up to 85% of such episodes. Rhinovirus is common in all age groups;
      respiratory syncytial virus (RSV) is most important in infants and young
      children. Knowledge of the immunopathogenetic mechanisms of virus infection in
      the asthmatic airway will lead to the development of new treatments for virus
      induced asthma.

PMID- 11997298
TI  - Macrophage defences against respiratory tract infections.
AB  - Pulmonary macrophages with a key role in defence against respiratory infection
      are a heterogeneous family of cells with phagocytic, antigen processing and
      immunomodulatory functions. Macrophages are important in both innate and acquired
      immunity in the respiratory tract, and have a role in lung defence against
      viruses, bacteria, mycobacteria and fungi. Interactions of pathogens with lung
      macrophages is strongly influenced by soluble immune components including
      complement, collectins and immunoglobulins. Macrophage function can be modulated
      by cytokines, environmental exposures, recent and chronic infection including HIV
      infection, drug therapy and gene transfer.

PMID- 11997299
TI  - Capsulate bacteria and the lung.
AB  - Capsulate bacteria cause the majority of community-acquired pneumonia presenting
      to hospital world-wide, at all ages. They are united by the virulence factor of
      their differing capsular polysaccharides, enabling them to evade phagocytosis.
      All cause invasive disease beyond the respiratory tract, including septicaemia
      and central nervous system infection. Recent advances in vaccine development have
      made the capsular polysaccharide an achievable target for vaccine strategies
      across all ages, with impacts already seen upon Streptococcus pneumoniae and
      Haemophilus influenzae type b pneumonia in countries able to afford these new
      vaccines.

PMID- 11997300
TI  - Persistent and aggressive bacteria in the lungs of cystic fibrosis children.
AB  - There have been enormous improvements in life expectancy of patients with cystic
      fibrosis, especially with improved nutrition and better understanding of the
      basic cellular defects. However, infection in particular with Pseudomonas
      aeruginosa and Burkholderia cepacia, has the greatest effect in decreasing life
      expectancy. Although infections can be prevented by rigorous infection control
      procedures, early aggressive antimicrobial chemotherapy and established infection
      managed by antibiotics, they are not completely effective. A greater
      understanding of how the bacteria evade the host defences and produce infection
      is needed.

PMID- 11997301
TI  - Recent advances in the rapid diagnosis of respiratory tract infection.
AB  - Molecular techniques have enabled major advances in the speed and sensitivity of
      the laboratory diagnosis of respiratory infections. Although the polymerase chain
      reaction is the most commonly used, there are several other methods available,
      which have applicability across the range of microbial pathogens.

PMID- 11997302
TI  - Assessment of the child with recurrent chest infections.
AB  - The child with recurrent chest infections presents the clinician with a difficult
      diagnostic challenge. Does the child have a simply-managed cause for their
      symptoms, such as recurrent viral respiratory infections or asthma, or is there
      evidence of a more serious underlying pathology, such as bronchiectasis? Many
      different disorders present in this way, including cystic fibrosis, a range of
      immunodeficiency syndromes, and congenital abnormalities of the respiratory
      tract. In some affected children, lung damage follows a single severe pneumonia:
      in others it is the result of inhalation of food or a foreign body. The
      assessment of these children is demanding: it requires close attention to the
      history and examination, and in selected cases, extensive investigations. Early
      and accurate diagnosis is essential to ensure that optimal treatment is given and
      to minimise the risk of progressive or irreversible lung damage. The aim of this
      chapter is to examine the causes of recurrent chest infections and to describe
      how this complex group of children should be assessed and investigated.

PMID- 11997303
TI  - HIV disease and respiratory infection in children.
AB  - Over one million children world-wide are living with HIV infection and
      respiratory disease is the commonest cause of morbidity and mortality in these
      children. The initial presentation of respiratory infection is usually in infancy
      or early childhood. There is enormous potential to prevent childhood HIV
      infection that is being realised in industrialised countries but not yet
      elsewhere. Increasingly, therefore, the burden of HIV disease is in children
      living in or from non-industrialised countries. This review describes and
      contrasts the pattern of respiratory infection from both regions. This pattern
      has changed with the implementation of PCP prophylaxis and the availability of
      potent antiretroviral therapy for children in resource-rich countries, such as
      the UK. More data are required from resource-poor regions such as tropical
      Africa, but it is clear that the major differences reflect greater background
      risk for respiratory infection and very limited management options rather than
      specific aetiology.

PMID- 11997304
TI  - Respiratory infections following haemopoietic stem cell transplantation in
      children.
AB  - Disorders of the respiratory system are well recognised following the
      administration of chemotherapy schedules; although respiratory complications may
      occur following less intensive regimens, they are most frequently seen following
      the administration of high dose chemotherapy with or without radiotherapy which
      is used in preparation for haemopoietic stem cell transplantation (SCT). In this
      setting, respiratory complications may occur in up to 50% of patients and account
      for over 40% of all deaths; those patients who require admission to intensive
      care (ICU) requiring intubation and mechanical ventilation have a particularly
      poor prognosis, with less than 10% becoming long-term survivors.

PMID- 11997305
TI  - Pneumocystis carinii.
AB  - Pneumocystis carinii is an atypical fungus that causes pneumonia in
      immunocompromised individuals. P. carinii comprises a heterogeneous group of
      organisms that have been isolated from a wide range of mammalian host species. P.
      carinii infection is host species specific, the P. carinii organisms that infect
      humans have only been found in humans. This review discusses the application of
      molecular techniques to the study of the biology and epidemiology of P. carinii
      infection. It addresses the use of DNA amplification for the detection and
      diagnosis of P. carinii pneumonia. Studies investigating the reservoir of
      infectious P. carinii organisms, the routes of transmission of the infection, and
      the emergence of drug resistant strains of P. carinii are also discussed.

PMID- 11997306
TI  - The management of croup.
AB  - Croup is a common paediatric respiratory illness involving inflammation and
      narrowing of the subglottic region of the larynx, frequently precipitated by
      viral infections. Treatment is aimed at decreasing symptoms and reducing
      inflammation. Glucocorticoids are effective by oral, parenteral or nebulized
      routes, and continue to provide the mainstay of therapy. The common oral
      dexamethasone dose (0.6 mg/kg) may exceed the dose required for good clinical
      efficacy. Nebulized epinephrine provides effective additional therapy for more
      severe cases. L-epinephrine appears to be comparable to racemic epinephrine,
      although further study is warranted. Limited data suggest that heliox is also
      effective in the short-term management of refractory croup. The use of humidified
      oxygen remains controversial, as good data are lacking.

PMID- 11997307
TI  - Radiological perspectives in empyema.
AB  - Empyema is a common cause for hospital admission in children. For years,
      clinicians have relied on chest X-rays to aid diagnosis and monitor treatment.
      New imaging techniques, particularly ultrasound, have helped in planning the
      management of children with empyema. Other cross-sectional radiological
      investigations are useful in a small proportion of children with complicated
      disease. The mainstays of imaging in the vast majority of children with empyema
      are chest radiography and ultrasound.

PMID- 11997308
TI  - Acute upper airway infections.
AB  - Upper respiratory tract infections are common and important. Although rarely
      fatal, they are a source of significant morbidity and carry a considerable
      economic burden. Numerous therapies for the common cold have no effect on
      symptoms or outcome. Complications such as cough are not improved by over-the
      counter preparations, while labelling cough alone as a symptom of asthma may
      result in unnecessary use of inhaled steroid treatment. Clinical presentation of
      sore throat does not accurately predict whether the infection is viral or
      bacterial, while throat culture and rapid antigen tests do not significantly
      change prescribing practice. Antibiotics have only a limited place in the
      management of recurrent sore throat due to group A beta-haemolytic streptococcal
      infection. Routine use of antibiotics in upper respiratory infection enhances
      parent belief in their effectiveness and increases the likelihood of future
      consultation in primary care for minor self-limiting illness. Respiratory viruses
      play a major role in the aetiology of acute otitis media (AOM); prevention
      includes the use of influenza or RSV vaccination, in addition to reducing other
      risk factors such as early exposure to respiratory viruses in day-care settings
      and to environmental tobacco smoke. The use of ventilation tubes (grommets) in
      secretory otitis media (SOM) remains controversial with conflicting data on
      developmental outcome and quality of life in young children. New conjugate
      pneumococcal vaccines appear safe in young children and prevent 6-7% of
      clinically diagnosed AOM.

PMID- 11997309
TI  - Treatment of infections due to resistant organisms.
AB  - Antibiotic resistance remains rare in paediatric community-acquired pneumonia in
      the UK, but is more common in hospital-acquired pneumonia and in patients with
      chronic lung diseases. It should also be considered in children arriving from
      countries with a high prevalence of antibiotic resistance, children with previous
      heavy antibiotic exposure, those who are immunosuppressed, and those who are not
      responding to conventional therapy. The most frequent bacterial cause of
      paediatric pneumonia is Streptococcus pneumoniae and globally there are major
      concerns about the increasing resistance of this organism to penicillin.
      Intermediate resistance may be overcome with conventional doses of parenteral
      penicillin and there is as yet no convincing evidence that intermediate/high
      level resistance is associated with a worse clinical outcome. Continued vigilance
      and research is required. The recently introduced pneumococcal conjugate vaccines
      offer great promise as they are likely to prevent cases of disease due to
      penicillin-resistant serotypes.

PMID- 11997310
TI  - Pneumonia due to viral and atypical organisms and their sequelae.
AB  - Most children presenting with pneumonia in the industrialised world will have a
      viral or 'atypical' organism. The clinical features of these 'atypical'
      pneumonias may be indistinguishable from bacterial pneumonia. New diagnostic
      techniques such as the polymerase chain reaction may help in diagnosis and choice
      of treatment, where appropriate. The pathological and clinical features of
      infection with each agent are discussed, together with their sequelae.

PMID- 11997311
TI  - Application of computed tomography in childhood respiratory infections.
AB  - The role of computed tomography (CT), including high-resolution computed
      tomography (HRCT), is still evolving in children. Radiation dose is an important
      consideration, but CT has advantages over chest radiography as it is more
      sensitive and specific for a variety of conditions affecting the pulmonary
      parenchyma. Careful attention to CT technique is vital for good quality
      diagnostic images in the paediatric population. The CT appearances of bacterial,
      viral, fungal, tuberculous and mycoplasma respiratory tract infections are
      discussed. The role of CT in specific circumstances such as the investigation of
      complicated bacterial pneumonia, the immunocompromised child and the sequelae of
      respiratory infections is addressed.

PMID- 11997312
TI  - Skeletal muscle regulates extracellular potassium.
AB  - Maintaining extracellular fluid (ECF) K(+) concentration ([K(+)]) within a narrow
      range is accomplished by the concerted responses of the kidney, which matches
      K(+) excretion to K(+) intake, and skeletal muscle, the main intracellular fluid
      (ICF) store of K(+), which can rapidly buffer ECF [K(+)]. In both systems,
      homologous P-type ATPase isoforms are key effectors of this homeostasis. During
      dietary K(+) deprivation, these P-type ATPases are regulated in opposite
      directions: increased abundance of the H,K-ATPase "colonic" isoform in the renal
      collecting duct drives active K(+) conservation while decreased abundance of the
      plasma membrane Na,K-ATPase alpha(2)-isoform leads to the specific shift of K(+)
      from muscle ICF to ECF. The skeletal muscle response is isoform and muscle
      specific: alpha(2) and beta(2), not alpha(1) and beta(1), levels are depressed,
      and fast glycolytic muscles lose >90% alpha(2), whereas slow oxidative muscles
      lose ~50%; however, both muscle types have the same fall in cellular [K(+)]. To
      understand the physiological impact, we developed the "K(+) clamp" to assess
      insulin-stimulated cellular K(+) uptake in vivo in the conscious rat by measuring
      the exogenous K(+) infusion rate needed to maintain constant plasma [K(+)] during
      insulin infusion. Using the K(+) clamp, we established that K(+) deprivation
      leads to near-complete insulin resistance of cellular K(+) uptake and that this
      insulin resistance can occur before any decrease in plasma [K(+)] or muscle Na(+)
      pump expression. These studies establish the advantage of combining molecular
      analyses of P-type ATPase expression with in vivo analyses of cellular K(+)
      uptake and excretion to determine mechanisms in models of disrupted K(+)
      homeostasis.

PMID- 11997313
TI  - Mesangial cell protein kinase C isozyme activation in the diabetic milieu.
AB  - High-glucose-induced activation of mesangial cell protein kinase C (PKC)
      contributes significantly to the pathogenesis of diabetic nephropathy. Excess
      glucose metabolism through the polyol pathway leads to de novo synthesis of both
      diacylglyerol (DAG) and phosphatidic acid, which may account for increased
      mesangial cell PKC-alpha, -beta, -delta, -epsilon, and -zeta
      activation/translocation observed within 48-h exposure to high glucose. Raised
      intracellular glucose causes generation of reactive oxygen species that may
      directly activate PKC isozymes and enhance their reactivity to vasoactive peptide
      signaling. In both diabetic rodent models of diabetes and cultured mesangial
      cells, PKC-beta appears to be the key isozyme required for the enhanced
      expression of transforming growth factor-beta(1), initiation of early
      accumulation of mesangial matrix protein, and increased microalbuminuria.
      Enhanced collagen IV expression by mesangial cells in response to vasoactive
      peptide hormone stimulation, e.g., endothelin-1, requires PKC-beta, -delta, 
      epsilon and -zeta. Loss of mesangial cell contractility to potent vasoactive
      peptides and coincident F-actin disassembly are due to high-glucose-activation of
      PKC-zeta. Inhibition of mesangial cell PKC isozyme activation in high glucose may
      prove to be the next important treatment for diabetic nephropathy.

PMID- 11997314
TI  - Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of
      mIMCD3 cells.
AB  - Raising osmolality to 700 mosmol/kgH(2)O by the addition of NaCl rapidly kills
      most murine inner renal medullary collecting duct cells (mIMCD3), but they
      survive at 500 mosmol/kgH(2)O. At 300 and 500 mosmol/kgH(2)O, NADH
      autofluorescence is present in a mitochondria-associated, punctate perinuclear
      pattern. Within 45 s to 30 min at 700 mosmol/kgH(2)O, the autofluorescence
      spreads diffusely throughout the cell. This correlates with mitochondrial
      membrane depolarization, measured as decreased tetramethylrhodamine methyl ester
      perchlorate (TMRM) fluorescence. Mitochondrial dysfunction should increase the
      cellular ADP/ATP ratio. In agreement, this ratio increases within 1-6 h.
      Mitochondrial morphology (transmission electron microscopy) is unaffected, but
      nuclear hypercondensation becomes evident. Progressive apoptosis occurs beginning
      1 h after osmolality is raised to 700, but not to 500, mosmol/kgH(2)O. General
      caspase activity and caspase-9 activity increase only after 6 h at 700
      mosmol/kgH(2)O. The mitochondrial Bcl-2/Bax ratio decreases within 1-3 h, but no
      cytochrome c release is evident. The mitochondria contain little p53 at any
      osmolality. Adding urea to 700 mosmol/kgH(2)O does not change NADH or TMRM
      fluorescence. We conclude that extreme acute hypertonicity causes a mitochondrial
      dysfunction involved in the initiation of apoptosis.

PMID- 11997315
TI  - Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure
      independent mechanism.
AB  - Hyperuricemia is associated with hypertension and vascular disease, but whether
      this represents a causal relationship or an epiphenomenon remains unknown. We
      recently reported a model of mild hyperuricemia in rats that results in increased
      blood pressure and mild renal fibrosis. In this study, we examined the effect of
      hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt
      diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05),
      hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and
      afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05).
      Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and
      arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia
      or arteriolopathy despite controlling blood pressure. In contrast, the
      arteriolopathy and hypertension were prevented by both enalapril and losartan.
      Uric acid also directly stimulated vascular smooth muscle cell proliferation in
      vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a
      renal arteriolopathy in rats that is blood pressure independent and involves the
      renin-angiotensin system.

PMID- 11997316
TI  - Aquaporin-2 localization in clathrin-coated pits: inhibition of endocytosis by
      dominant-negative dynamin.
AB  - Before the identification of aquaporin (AQP) proteins, vasopressin-regulated
      "water channels" were identified by freeze-fracture electron microscopy as
      aggregates or clusters of intramembraneous particles (IMPs) on hormonally
      stimulated target cell membranes. In the kidney collecting duct, these IMP
      clusters were subsequently identified as possible sites of clathrin-coated pit
      formation on the plasma membrane, and a clathrin-mediated mechanism for
      internalization of vasopressin-sensitive water channels was suggested. Using an
      antibody raised against the extracellular C loop of AQP2, we now provide direct
      evidence that AQP2 is concentrated in clathrin-coated pits on the apical surface
      of collecting duct principal cells. Furthermore, by using a fracture-label
      technique applied to LLC-PK(1) cells expressing an AQP2-c-myc construct, we show
      that AQP2 is located in IMP aggregates and is concentrated in shallow membrane
      invaginations on the surface of forskolin-stimulated cells. We also studied the
      functional role of clathrin-coated pits in AQP2 trafficking by using a GTPase
      deficient dynamin mutation (K44A) to inhibit clathrin-mediated endocytosis.
      Immunofluorescence labeling and freeze-fracture electron microscopy showed that
      dominant-negative dynamin 1 and dynamin 2 mutants prevent the release of clathrin
      coated pits from the plasma membrane and induce an accumulation of AQP2 on the
      plasma membrane of AQP2-transfected cells. These data provide the first direct
      evidence that AQP2 is located in clathrin-coated pits and show that AQP2 recycles
      between the plasma membrane and intracellular vesicles via a dynamin-dependent
      endocytotic pathway. We propose that the IMP clusters previously associated with
      vasopressin action represent sites of dynamin-dependent, clathrin-mediated
      endocytosis in which AQP2 is concentrated before internalization.

PMID- 11997317
TI  - Ischemia induces alterations in actin filaments in renal vascular smooth muscle
      cells.
AB  - Although altered renal vascular reactivity is known to occur after ischemia, the
      structural basis explaining the phenomenon has not been clarified. To evaluate
      for structural damage to the renal vasculature in ischemic acute renal failure
      (ARF), F-actin in the renal vasculature of rat kidneys and cultured vascular
      smooth muscle cells was examined using confocal fluorescence microscopy. The left
      renal artery was clamped for 15 or 45 min in Sprague-Dawley rats. In other
      experimental groups, 45 min of renal arterial clamping was followed by 1 or 3 h
      of reperfusion. Control kidneys were procured without any preceding
      interventional procedure. F-actin was labeled with either fluorescein or Texas
      red-conjugated phalloidin. Serial optical sections were collected by confocal
      microscopy, and image volumes were rendered three dimensionally. The degree of
      cytoskeletal damage in the vasculature was assessed by semiquantitative scoring
      of the staining for F-actin. Disorganization/disarray of F-actin, reflected by
      disruption and clumping of the actin filaments, was observed in arteries,
      arterioles, and the vasa rectae of the kidney after ischemia or ischemia
      reperfusion. Smooth muscle cells from arteries and arterioles showed significant
      damage to F-actin after either 15 or 45 min of ischemia in a duration-dependent
      manner. The actin cytoskeleton tended to recover from damage from 45 min of
      ischemia 1 and 3 h after reperfusion. The vasa rectae did not demonstrate
      significant damage to F-actin after 15- or 45-min ischemia. However, significant
      damage to the vasa rectae was manifest 3 h after the reperfusion following 45 min
      of ischemia. In summary, disorganization/disarray of F-actin in vascular smooth
      muscle cells of the kidney was observed after ischemia or ischemia-reperfusion. A
      similar finding was observed in cultured vascular smooth muscle cells. We suggest
      that this disorganization of the actin cytoskeleton may play a contributory role
      in the loss of autoregulation of renal blood flow and the aberrant vascular
      reactivity in postischemic ARF.

PMID- 11997318
TI  - CD40 ligation stimulates MCP-1 and IL-8 production, TRAF6 recruitment, and MAPK
      activation in proximal tubule cells.
AB  - The mechanism of CD40/CD154-induced chemokine production and its potential role
      in renal inflammatory disease were explored. Human proximal tubule cells
      maintained in primary culture were used as the experimental model. With the use
      of immunocytochemistry, confocal microscopy, and a cell fractionation assay, the
      CD40 receptor was found to be expressed in the cell membrane of the epithelial
      cell, and, on engagement by CD154, its cognate ligand, translocated to the
      cytoplasmic compartment. Engagement of CD40 by CD154 stimulated interleukin-8 (IL
      8) and monocyte chemoattractant protein-1 (MCP-1) production, which proceeded via
      receptor activation of the extracellular signal-regulated kinase (ERK)1/2, stress
      activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK), and p38
      mitogen-activated protein kinase (MAPK) pathways. CD40 ligation also engaged
      tumor necrosis factor receptor-activating factor 6 (TRAF6), as evidenced by
      colocalization of the activated receptor with TRAF6 in the cytoplasmic
      compartment, translocation of both proteins from the insoluble to the soluble
      cell fraction, and coimmunoprecipitation of the two proteins only under ligand
      stimulated conditions. Furthermore, an antisense oligodeoxyribonucleotide
      targeted against TRAF6 mRNA blunted p38 and SAPK/JNK but not ERK1/2 MAPK
      activities, as well as IL-8 and MCP-1 production, arguing that TRAF6 is an
      upstream activator. The zinc chelator TPEN, but not the calcium chelator BAPTA,
      obliterated CD154-evoked MAPK activity and chemokine production, providing
      indirect evidence for protein-protein interactions playing a critical role in
      CD40 signaling in these cells. We conclude that in human proximal tubule cells,
      CD40 and TRAF6 reside in separate low-density, detergent-insoluble membrane
      microdomains, or rafts, and on activation translocate and associate with one
      another probably via zinc-finger domains in the soluble or cytoplasmic
      compartment. TRAF6, in turn, activates SAPK/JNK and p38 MAPK phosphorylation,
      which in turn stimulates IL-8 and MCP-1 production in these cells.

PMID- 11997319
TI  - Expression, localization, and regulation of aquaporin-1 to -3 in rat urothelia.
AB  - Although mammalian urothelia are generally considered impermeable to constituents
      of urine, in vivo studies in several species indicate urothelial transport of
      water and solutes under certain conditions. This study investigates the
      expression, localization, and regulation of aquaporin (AQP)-1, -2, and -3 in
      ureteral and bladder tissues in 48-h dehydrated and water-loaded female Wistar
      rats. Immunoblots of homogenates of whole ureter and bladder identified
      characteristic approximately 28- and 35- to 44-kDa bands for AQP-1, -2, and -3.
      AQP-1 was localized to capillary and arteriole endothelial cells, whereas AQP-2
      and -3 circumferentially lined the epithelial cell membranes except for the
      apical membrane of the epithelial cells adjacent to the lumens of both ureter and
      bladder. AQP-2 was also present in epithelial cell cytoplasm. Dehydration
      resulted in 160-200% increases of AQP-3 signal and 24-49% increases of AQP-2
      signal but no change in AQP-1 signal on immunoblots of homogenates of ureters and
      bladders. AQPs in genitourinary tract urothelia likely play a role in the
      regulation of epithelial cell volume and osmolality and may play a role in bulk
      water movement across urothelia.

PMID- 11997320
TI  - Renal nerve stimulation augments effect of intraluminal angiotensin II on
      proximal tubule transport.
AB  - The proximal tubule synthesizes and secretes angiotensin II into the lumen, where
      it regulates transport. Renal denervation abolishes the effect of angiotensin II
      on proximal tubule transport. Using in vivo microperfusion, we examined whether
      renal nerve stimulation modulates the effect of angiotensin II on transport. The
      effect of angiotensin II was assessed by measuring the decrease in volume
      reabsorption with the addition of 10(-4) M luminal enalaprilat. Luminal
      enalaprilat did not alter volume reabsorption (2.80 +/- 0.18 vs. 2.34 +/- 0.14 nl
      x mm(-1) x min(-1)). However, with renal nerve stimulation, enalaprilat decreased
      volume reabsorption (3.45 +/- 0.22 vs. 1.67 +/- 0.20 nl x mm(-1) x min(-1), P <
      0.0005). The absolute and percent decrements in volume reabsorption with luminal
      enalaprilat were higher with renal nerve stimulation than with native innervation
      (1.78 +/- 0.19 vs. 0.46 +/- 0.23 nl x mm(-1) x min(-1), P < 0.02, and 51.8 +/-
      5.0 vs. 14.6 +/- 7.4%, P < 0.05, respectively). Renal nerve stimulation did not
      alter the glomerular filtration rate or renal blood flow. Renal nerve stimulation
      augments the stimulatory effect of intraluminal angiotensin II. The sympathetic
      renal nerves modulate the proximal tubule renin-angiotensin system and thereby
      regulate proximal tubule transport.

PMID- 11997321
TI  - Mechanisms used to dispose of progressively increasing alkali load in rats.
AB  - Our objective was to describe the process of alkali disposal in rats. Balance
      studies were performed while incremental loads of alkali were given to rats fed a
      low-alkali diet or their usual alkaline ash diet. Control groups received
      equimolar NaCl or KCl. Virtually all of the alkali was eliminated within 24 h
      when the dose exceeded 750 micromol. The most sensitive response to alkali input
      was a decline in the excretion of NH(4)(+). The next level of response was to
      increase the excretion of unmeasured anions; this rise was quantitatively the
      most important process in eliminating alkali. The maximum excretion of citrate
      was approximately 70% of its filtered load. An even higher alkali load augmented
      the excretion of 2-oxoglutarate to >400% of its filtered load. Only with the
      largest alkali load did bicarbonaturia become quantitatively important. We
      conclude that renal mechanisms eliminate alkali while minimizing bicarbonaturia.
      This provides a way of limiting changes in urine pH without sacrificing acid-base
      balance, a process that might lessen the risk of kidney stone formation.

PMID- 11997322
TI  - ERK mediates inhibition of Na(+)/H(+) exchange and HCO(3)(-) absorption by nerve
      growth factor in MTAL.
AB  - Mitogen-activated protein (MAP) kinases mediate a variety of critical cellular
      events, but their role in the regulation of epithelial transport is largely
      undefined. Recently, we demonstrated that nerve growth factor (NGF) inhibits
      HCO(3)(-) absorption in the rat medullary thick ascending limb (MTAL) through an
      unusual mechanism: 1) NGF inhibits basolateral membrane Na(+)/H(+) exchange
      activity, an effect opposite to the stimulation of Na(+)/H(+) exchange by growth
      factors in other cells; and 2) inhibition of basolateral Na(+)/H(+) exchange
      results secondarily in inhibition of apical Na(+)/H(+) exchange, thereby
      inhibiting HCO(3)(-) absorption. In this study, we examined the role of MAP
      kinases in mediating inhibition by NGF. In tissue strips from the inner stripe of
      the outer medulla and in microdissected MTALs, NGF increased extracellular signal
      regulated kinase (ERK) activity twofold but had no effect on c-Jun NH(2)-terminal
      kinase (JNK) or p38 MAP kinase activity. The selective MAP kinase kinase (MEK1/2)
      inhibitors U0126 and PD-98059 abolished the NGF-induced ERK activation and
      largely eliminated (> or = 60%) the effects of NGF to inhibit basolateral
      Na(+)/H(+) exchange activity and transepithelial HCO absorption in perfused
      MTALs. The MEK1/2 inhibitors did not affect inhibition of HCO(3)(-) absorption by
      bath ethylisopropyl amiloride, indicating that ERK activation is not involved in
      mediating interaction between the basolateral and apical Na(+)/H(+) exchangers.
      These results demonstrate that NGF inhibits basolateral Na(+)/H(+) exchange
      activity and HCO(3)(-) absorption in the MTAL through activation of the ERK
      signaling pathway. These findings identify a novel action of ERK to inhibit
      Na(+)/H(+) exchange activity and establish a role for MAP kinase pathways in the
      acute regulation of Na(+)/H(+) exchange activity and transepithelial acid
      secretion in renal tubules.

PMID- 11997323
TI  - Control of descending vasa recta pericyte membrane potential by angiotensin II.
AB  - Using nystatin perforated-patch whole cell recording, we investigated the role of
      Cl(-) conductance in the modulation of outer medullary descending vasa recta
      (OMDVR) pericyte membrane potential (Psi m) by ANG II. ANG II (10(-11) to 10(-7)
      M) consistently depolarized OMDVR and induced Psi m oscillations at lower
      concentrations. The Cl(-) channel blockers anthracene-9-decarboxylate (1 mM) and
      niflumic acid (10 microM) hyperpolarized resting pericytes and repolarized ANG II
      treated pericytes. In voltage-clamp experiments, ANG II-treated pericytes
      exhibited slowly activating currents that were nearly eliminated by treatment
      with niflumic acid (10 microM) or removal of extracellular Ca(2+). Those currents
      reversed at -31 and -10 mV when extracellular Cl(-) concentration was 152 and 34
      mM, respectively. In pericytes held at -70 mV, oscillating inward currents were
      sometimes observed; the reversal potential also shifted with extracellular Cl(-)
      concentration. We conclude that ANG II activates a Ca(2+)-dependent Cl(-)
      conductance in OMDVR pericytes to induce membrane depolarization and Psi m
      oscillations.

PMID- 11997324
TI  - Estrogen-induced proliferation of urothelial cells is modulated by nerve growth
      factor.
AB  - Both nerve growth factor (NGF) and estrogen have been shown to stimulate
      proliferation of various cell types. Human urothelial cells (HUC) express the
      alpha- and beta-subtypes of the estrogen receptor (ER(alpha) and ER(beta)) as
      well as tyrosine kinase A (trkA), the high-affinity receptor for NGF. We
      investigated interactions between estrogen and NGF relative to cell proliferation
      using primary cultures of HUC. 17 beta-estradiol (E2) stimulated NGF synthesis by
      HUC, and E2 (50 nM), the ER(alpha) agonist 16 alpha-iodo-17 beta-estradiol (10
      nM), or the ER(beta) agonist genistein (50 nM) each stimulated HUC proliferation,
      an effect that was abolished by the estrogen antagonist ICI-182,780 (100 nM). NGF
      (1-100 ng/ml) stimulated HUC proliferation, and this was abolished by NGF
      antiserum (0.1 microl/ml) or the trkA antagonist K252a (100 nM). HUC
      proliferation stimulated by E2 was also abolished by NGF antiserum or K252a.
      Finally, we observed that treatment of HUC with NGF (50 ng/ml) or E2 (50 nM)
      stimulated trkA phosphorylation, and this was abolished by K252a (100 nM) or NGF
      antiserum (0.1 microl/ml). These data indicate that the effects of ER activation
      on HUC proliferation at least partly involve activation of trkA by NGF.

PMID- 11997325
TI  - Role of cAMP-PKA-PLC signaling cascade on dopamine-induced PKC-mediated
      inhibition of renal Na(+)-K(+)-ATPase activity.
AB  - We studied the molecular events set into motion by stimulation of D(1)-like
      receptors downstream of Na(+)-K(+)-ATPase, while measuring apical-to-basal
      ouabain-sensitive, amphotericin B-induced increases in short-circuit current in
      opossum kidney (OK) cells. The D(1)-like receptor agonist SKF-38393 decreased
      Na(+)-K(+)-ATPase activity (IC(50), 130 nM). This effect was prevented by the
      D(1)-like receptor antagonist SKF-83566, overnight cholera toxin treatment, the
      protein kinase A (PKA) antagonist H-89, or the PKC antagonist chelerythrine, but
      not the mitogen-activated PK inhibitor PD-098059 or phosphatidylinositol 3-kinase
      inhibitors wortmannin and LY-294002. Dibutyryl cAMP (DBcAMP) and phorbol 12,13
      dibutyrate (PDBu) both effectively reduced Na(+)-K(+)-ATPase activity. PKA
      downregulation abolished the inhibitory effects of SKF-38393 and DBcAMP but not
      those of PDBu. PKC downregulation abolished inhibition by PDBu, SKF-38393, and
      DBcAMP. The phospholipase C (PLC) inhibitor U-73122 prevented inhibition by SKF
      38393 and DBcAMP. However, DBcAMP increased PLC activity. Although OK cells
      express both G(s)alpha and G(q/11)alpha proteins, D(1)-like receptors are coupled
      to G(s)alpha proteins only, as evidenced by studies in cells treated overnight
      with specific antibodies raised against G(s)alpha and G(q/11)alpha proteins. We
      conclude that PLC and Na(+)-K(+)-ATPase are effector proteins for PKA and PKC,
      respectively, after stimulation of D(1)-like receptors coupled to G(s)alpha
      proteins, in a sequence of events that begins with adenylyl cyclase-PKA system
      activation followed by PLC-PKC system activation.

PMID- 11997326
TI  - Identification of lactate as a driving force for prostanoid transport by
      prostaglandin transporter PGT.
AB  - We previously characterized the prostaglandin (PG) transporter PGT as an
      exchanger in which [(3)H]PGE(2) influx is coupled to the efflux of a
      countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT
      under conditions known to favor glycolysis (glucose as a carbon source) or
      oxidative phosphorylation (glutamine as a carbon source) and studied the effect
      on PGT-mediated [(3)H]PGE(2) influx. PGT-expressing cells grown in glutamine
      exhibited a 2- to 4-fold increase in [(3)H]PGE(2) influx compared with the
      antisense control, whereas cells grown in glucose exhibited a 14-fold increase.
      In the presence of 10 vs. 25 mM glucose during the uptake, there was a dose
      dependent increment in [(3)H]PGE(2) influx. Cis inhibition of [(3)H]PGE(2) influx
      occurred with lactate at physiological concentrations (apparent K(m) = 48 +/- 12
      mM). Preloading with lactate caused a dose-dependent trans stimulation of PGT
      mediated [(3)H]PGE(2) uptake, and external lactate caused trans stimulation of
      PGT-mediated [(3)H]PGE(2) release. Together, these data are consistent with PGT
      mediated PG-lactate exchange. Cells engaged in glycolysis would then be poised
      energetically for prostanoid uptake by means of PGT.

PMID- 11997327
TI  - Prostaglandin transporter PGT is expressed in cell types that synthesize and
      release prostanoids.
AB  - PGT is a broadly expressed transporter of prostaglandins (PGs) and thromboxane
      that is energetically poised to take up prostanoids across the plasma membrane.
      To gain insight into the function of PGT, we generated mouse monoclonal antibody
      20 against a portion of putative extracellular loop 5 of rat PGT. Immunoblots of
      endogenous PGT in rat kidney revealed a 65-kDa protein in a zonal pattern
      corresponding to PG synthesis rates (papilla congruent with medulla > cortex).
      Immunocytochemically, PGT in rat kidneys was expressed in glomerular endothelial
      and mesangial cells, arteriolar endothelial and muscularis cells, principal cells
      of the collecting duct, medullary interstitial cells, medullary vasa rectae
      endothelia, and papillary surface epithelium. Proximal tubules, which are known
      to take up and metabolize PGs, were negative. Immunoblotting and
      immunocytochemistry revealed that rat platelets also express abundant PGT.
      Coexpression of the PG synthesis apparatus (cyclooxygenase) and PGT by the same
      cell suggests that prostanoids may undergo release and reuptake.

PMID- 11997328
TI  - Production of superoxide through NADH oxidase in thick ascending limb of Henle's
      loop in rat kidney.
AB  - We recently reported that NADH oxidase is one of the major enzymes responsible
      for superoxide (O(2)(-)*) production in the rat kidney. However, the functional
      significance of NADH oxidase-mediated O. production and the mechanisms regulating
      this enzyme activity are poorly understood. Using fluorescence microscopic
      imaging analysis, the present study demonstrated that thick ascending limbs of
      Henle's loop (TALHs) exhibited red fluorescence when incubated with
      dihydroethidium (DHE), suggesting that O(2)(-)* is produced in this tubular
      segment. Compared with other nephron segments, TALHs from both renal cortex and
      medulla showed the highest fluorescence intensity. By incubating cortical TALHs
      (cTALHs) with the substrates of NADH oxidase, xanthine oxidase, nitric oxide
      synthase, arachidonic acid-metabolizing enzymes, and intramitochondrial oxidases,
      NADH oxidase was found to be one of the most important enzymes for O(2)(-)*
      production in this tubular segment. The NADH oxidase inhibitor
      diphenyleneiodonium (DPI; 100 microM) completely blocked NADH-induced O(2)(-)*
      production in cTALHs. Exposure of cTALHs to low PO(2) (5-10 Torr) significantly
      increased O(2)(-)* production regardless of the absence or presence of NADH.
      Furthermore, angiotensin II (100 nM) increased NADH oxidase activity by 32%,
      which was completely blocked by DPI. These results suggest that NADH oxidase is a
      major enzyme responsible for O(2)(-)* production in the TALHs and that the
      production of O(2)(-)* via NADH oxidase may be regulated by renal tissue
      oxygenation and circulating hormones.

PMID- 11997329
TI  - Mechanisms through which ammonia regulates cortical collecting duct net proton
      secretion.
AB  - Ammonia stimulates cortical collecting duct (CCD) net bicarbonate reabsorption by
      activating an apical H(+)-K(+)-ATPase through mechanisms that are independent of
      ammonia's known effects on intracellular pH and active sodium transport. The
      present studies examined whether this stimulation occurs through soluble N
      ethylmaleimide-sensitive fusion attachment receptor (SNARE) protein-mediated
      vesicle fusion. Rabbit CCD segments were studied using in vitro microperfusion,
      and transepithelial bicarbonate transport was measured using microcalorimetry.
      Ammonia's stimulation of bicarbonate reabsorption was blocked by either chelating
      intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid acetoxymethyl ester or by inhibiting microtubule polymerization with
      colchicine compared with parallel studies performed in the absence of these
      inhibitors. An inactive structural analog of colchicine, lumicolchicine, did not
      alter ammonia's stimulation of bicarbonate reabsorption. Tetanus toxin, a zinc
      endopeptidase specific for vesicle-associated SNARE (v-SNARE) proteins, prevented
      ammonia from stimulating net bicarbonate reabsorption. Consistent with the
      functional evidence for v-SNARE involvement, antibodies directed against a
      conserved region of isoforms 1-3 of the tetanus toxin-sensitive, vesicle
      associated membrane protein (VAMP) members of v-SNARE proteins labeled the apical
      and subapical region of collecting duct intercalated cells. Similarly, antibodies
      to NSF protein, a protein involved in activation of SNARE proteins for subsequent
      vesicle fusion, localized to the apical and subapical region of collecting duct
      intercalated cells. These results indicate that ammonia stimulates CCD
      bicarbonate reabsorption through an intracellular calcium-dependent, microtubule
      dependent, and v-SNARE-dependent mechanism that appears to involve insertion of
      cytoplasmic vesicles into the apical plasma membrane of CCD intercalated cells.

PMID- 11997330
TI  - PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange
      regulatory factor-2.
AB  - The transmembrane sialoglycoprotein podocalyxin is thought to be essential in the
      fine interdigitating foot process structure of the podocyte. The intracellular
      COOH-terminal amino acids Asp-Thr-His-Leu (DTHL) of podocalyxin comprise a
      putative ligand for a type I PSD95-Dlg-zona occludens-1 (PDZ) domain. A 20-amino
      acid synthetic peptide containing this motif was used to screen a cDNA library,
      and clones of rabbit Na(+)/H(+) exchange regulatory factor-2 (NHERF-2) were
      obtained. In vitro analysis demonstrated that each PDZ domain of NHERF-2 could
      bind podocalyxin independently. NHERF-2 coprecipitated from glomerular extracts
      with podocalyxin, and podocalyxin and NHERF-2 colocalized in the glomerular
      capillary loops, indicating that podocalyxin and NHERF-2 may interact in vivo.
      Podocalyxin peptide missing the terminal leucine (-DTHL) failed to interact with
      NHERF-2 in vitro. Podocalyxin localized to the apical membrane of transfected
      Madin-Darby canine kidney (MDCK) cells. However, mutant podocalyxin (missing a
      functional DTHL COOH-terminal motif) showed cytoplasmic and apical membrane
      localization in transfected cells and was also less stable at the apical
      membrane, as assessed by confocal microscopy and biotinylation studies. Mutant
      podocalyxin did lower the transepithelial resistance of MDCK cell monolayers,
      albeit to a lesser extent than full-length podocalyxin. We conclude that
      podocalyxin can interact with both PDZ domains of NHERF-2 and that this
      interaction requires the intact COOH terminus of podocalyxin, which is also
      responsible for the efficient apical localization of podocalyxin in transfected
      MDCK cells. These results suggest that the interaction of podocalyxin with NHERF
      2 may function to efficiently retain podocalyxin at the apical surface of the
      podocyte and provide a mechanism linking podocalyxin to the actin cytoskeleton.

PMID- 11997331
TI  - Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted
      endothelial cells.
AB  - There is accumulating circumstantial evidence suggesting that endothelial cell
      dysfunction contributes to the "no-reflow" phenomenon in postischemic kidneys.
      Here, we demonstrated the vulnerability of in vitro, ex vivo, and in vivo
      endothelial cells exposed to pathophysiologically relevant insults, such as
      oxidative and nitrosative stress or ischemia. All of these stimuli compromised
      the integrity of the endothelial lining. Next, we performed minimally invasive
      intravital microscopy of blood flow in peritubular capillaries, which provided
      direct evidence of the existence of the no-reflow phenomenon, attributable, at
      least in part, to endothelial injury. In an attempt to ameliorate the hemodynamic
      consequences of lost endothelial integrity, we transplanted endothelial cells or
      surrogate cells expressing endothelial nitric oxide synthase into rats subjected
      to renal artery clamping. Implantation of endothelial cells or their surrogates
      expressing functional endothelial nitric oxide synthase in the renal
      microvasculature resulted in a dramatic functional protection of ischemic
      kidneys. These observations strongly suggest that endothelial cell dysfunction is
      the primary cause of the no-reflow phenomenon, which, when ameliorated, results
      in prevention of renal injury seen in acute renal failure.

PMID- 11997332
TI  - Intravital videomicroscopy of peritubular capillaries in renal ischemia.
AB  - The recent refinement and computerization of intravital microscopy have permitted
      us to monitor microcirculation in vivo with minimal invasion. Here, we report on
      the first findings made with the use of a pencil-lens intravital microscope as
      applied to the ischemic rat kidney. Peritubular capillary and glomerular blood
      flow were monitored under basal conditions, during renal artery occlusion, and
      immediately after release of the clamp. Erythrocyte velocity was calculated as an
      angle in consecutive spatiotemporal images. Intravital videomicroscopy during the
      reperfusion period showed intermittent cessation and partial recovery of blood
      flow in both peritubular and glomerular capillaries. Blood flow was uniformly
      orthograde under control conditions; however, the retrograde flow occurred on
      reperfusion. The patency of peritubular capillaries was partially compromised
      during the early reperfusion period but rapidly recovered. The recovery of
      glomerular microcirculation occurred faster than that of peritubular capillaries.
      We suggest that a functional vasculopathy develops very early in the course of
      ischemia-reperfusion in superficial cortical microvasculature and is more
      pronounced in peritubular capillaries, thus accounting for the development of
      patchy injury of tubular epithelia.

PMID- 11997333
TI  - What is finished, and why does it matter.

PMID- 11997334
TI  - Biomedical applications and studies of molecular evolution: a proposal for a
      primate genomic library resource.
AB  - The anticipated completion of two of the most biomedically relevant genomes,
      mouse and human, within the next three years provides an unparalleled opportunity
      for the large-scale exploration of genome evolution. Targeted sequencing of
      genomic regions in a panel of primate species and comparison to reference genomes
      will provide critical insight into the nature of single-base pair variation,
      mechanisms of chromosomal rearrangement, patterns of selection, and species
      adaptation. Although not recognized as model "genetic organisms" because of their
      longevity and low fecundity, 30 of the approximately 300 primate species are
      targets of biomedical research. The existence of a human reference sequence and
      genomic primate BAC libraries greatly facilitates the recovery of genes/genomic
      regions of high biological interest because of an estimated maximum neutral
      nucleotide sequence divergence of 25%. Primate species, therefore, may be
      regarded as the ideal model "genomic organisms". Based on existing BAC library
      resources, we propose the construction of a panel of primate BAC libraries from
      phylogenetic anchor species for the purpose of comparative medicine as well as
      studies of genome evolution.

PMID- 11997335
TI  - Time for a unified system of mutation description and reporting: a review of
      locus-specific mutation databases.
AB  - Mutation databases of human genes are assuming an increasing importance in all
      areas of health care. In addition, more and more experts in the mutations and
      diseases of particular genes are curating published and unpublished mutations in
      locus-specific databases (LSDB). These databases contain such extensive
      information that they have become known as knowledge bases. We analyzed these
      databases and their content between June 21, 2001, and July 18, 2001. We were
      able to access 94 independent websites devoted to the documentation of mutation
      containing 262 LSDBs for study. We analyzed one LSDB from each of these websites
      (i.e., 94 LSDBs) for the presence or absence of 80 content criteria, as generally
      each gene in a multigene website documented the same criteria. No criterion
      studied gave unanimous agreement in every database. Twenty-two genes were
      represented by more than one LSDB. The number of mutations recorded, excluding
      p53, was 23,822 with 1518 polymorphisms. Fifty-four percent of the LSDBs studied
      were easy to use and 11% hard to follow; 73% of the databases were displayed
      through HTML. Three databases were found that were given a high score for ease of
      use and wealth of content. Thus, the study provided a strong case for uniformity
      of data to make the content maximally useful. In this direction, a hypothetical
      content for an ideal LSDB was derived. We also derived a community structure that
      would enhance the chances of mutation capture rather than being left unpublished
      in a patient's report. We hope the interested community and granting bodies will
      assist in achieving the vision of a public system that collects and displays all
      variants discovered.

PMID- 11997336
TI  - A complete sequence of the T. tengcongensis genome.
AB  - Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic
      eubacterium that was isolated from a freshwater hot spring in Tengchong, China.
      Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an
      isolate, MB4(T) (Genbank accession no. AE008691). The genome encodes 2588
      predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified
      according to homology to other documented proteins, and the rest, 824 CDS
      (31.8%), are functionally unknown. One of the interesting features of the T.
      tengcongensis genome is that 86.7% of its genes are encoded on the leading strand
      of DNA replication. Based on protein sequence similarity, the T. tengcongensis
      genome is most similar to that of Bacillus halodurans, a mesophilic eubacterium,
      among all fully sequenced prokaryotic genomes up to date. Computational analysis
      on genes involved in basic metabolic pathways supports the experimental discovery
      that T. tengcongensis metabolizes sugars as principal energy and carbon source
      and utilizes thiosulfate and element sulfur, but not sulfate, as electron
      acceptors. T. tengcongensis, as a gram-negative rod by empirical definitions
      (such as staining), shares many genes that are characteristics of gram-positive
      bacteria whereas it is missing molecular components unique to gram-negative
      bacteria. A strong correlation between the G + C content of tDNA and rDNA genes
      and the optimal growth temperature is found among the sequenced thermophiles. It
      is concluded that thermophiles are a biologically and phylogenetically divergent
      group of prokaryotes that have converged to sustain extreme environmental
      conditions over evolutionary timescale.

PMID- 11997337
TI  - Identification of a novel cis-regulatory element involved in the heat shock
      response in Caenorhabditis elegans using microarray gene expression and
      computational methods.
AB  - We report here the identification of a previously unknown transcription
      regulatory element for heat shock (HS) genes in Caenorhabditis elegans. We
      monitored the expression pattern of 11,917 genes from C. elegans to determine the
      genes that were up-regulated on HS. Twenty eight genes were observed to be
      consistently up-regulated in several different repetitions of the experiments. We
      analyzed the upstream regions of these genes using computational DNA pattern
      recognition methods. Two potential cis-regulatory motifs were identified in this
      way. One of these motifs (TTCTAGAA) was the DNA binding motif for the heat shock
      factor (HSF), whereas the other (GGGTGTC) was previously unreported in the
      literature. We determined the significance of these motifs for the HS genes using
      different statistical tests and parameters. Comparative sequence analysis of
      orthologous HS genes from C. elegans and Caenorhabditis briggsae indicated that
      the identified DNA regulatory motifs are conserved across related species. The
      role of the identified DNA sites in regulation of HS genes was tested by in vitro
      mutagenesis of a green fluorescent protein (GFP) reporter transgene driven by the
      C. elegans hsp-16-2 promoter. DNA sites corresponding to both motifs are shown to
      play a significant role in up-regulation of the hsp-16-2 gene on HS. This is one
      of the rare instances in which a novel regulatory element, identified using
      computational methods, is shown to be biologically active. The contributions of
      individual sites toward induction of transcription on HS are nonadditive, which
      indicates interaction and cross-talk between the sites, possibly through the
      transcription factors (TFs) binding to these sites.

PMID- 11997338
TI  - Genes in a refined Smith-Magenis syndrome critical deletion interval on
      chromosome 17p11.2 and the syntenic region of the mouse.
AB  - Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation
      syndrome associated with behavioral abnormalities and sleep disturbance. Most
      patients have the same approximately 4 Mb interstitial genomic deletion within
      chromosome 17p11.2. To investigate the molecular bases of the SMS phenotype, we
      constructed BAC/PAC contigs covering the SMS common deletion interval and its
      syntenic region on mouse chromosome 11. Comparative genome analysis reveals the
      absence of all three approximately 200-kb SMS-REP low-copy repeats in the mouse
      and indicates that the evolution of SMS-REPs was accompanied by transposition of
      adjacent genes. Physical and genetic map comparisons in humans reveal reduced
      recombination in both sexes. Moreover, by examining the deleted regions in SMS
      patients with unusual-sized deletions, we refined the minimal Smith-Magenis
      critical region (SMCR) to an approximately 1.1-Mb genomic interval that is
      syntenic to an approxiamtely 1.0-Mb region in the mouse. Genes within the SMCR
      and its mouse syntenic region were identified by homology searches and by gene
      prediction programs, and their gene structures and expression profiles were
      characterized. In addition to 12 genes previously mapped, we identified 8 new
      genes and 10 predicted genes in the SMCR. In the mouse syntenic region of the
      human SMCR, 16 genes and 6 predicted genes were identified. The SMCR is highly
      conserved between humans and mice, including 19 genes with the same gene order
      and orientation. Our findings will facilitate both the identification of gene(s)
      responsible for the SMS phenotype and the engineering of an SMS mouse model.

PMID- 11997339
TI  - Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS
      REPs.
AB  - An approximately 4-Mb genomic segment on chromosome 17p11.2, commonly deleted in
      patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with
      dup(17)(p11.2p11.2) syndrome, is flanked by large, complex low-copy repeats
      (LCRs), termed proximal and distal SMS-REP. A third copy, the middle SMS-REP, is
      located between them. SMS-REPs are believed to mediate nonallelic homologous
      recombination, resulting in both SMS deletions and reciprocal duplications. To
      delineate the genomic structure and evolutionary origin of SMS-REPs, we
      constructed a bacterial artificial chromosome/P1 artificial chromosome contig
      spanning the entire SMS region, including the SMS-REPs, determined its genomic
      sequence, and used fluorescence in situ hybridization to study the evolution of
      SMS-REP in several primate species. Our analysis shows that both the proximal SMS
      REP (approximately 256 kb) and the distal copy (approximately 176 kb) are located
      in the same orientation and derived from a progenitor copy, whereas the middle
      SMS-REP (approximately 241 kb) is inverted and appears to have been derived from
      the proximal copy. The SMS-REP LCRs are highly homologous (>98%) and contain at
      least 14 genes/pseudogenes each. SMS-REPs are not present in mice and were
      duplicated after the divergence of New World monkeys from pre-monkeys
      approximately 40-65 million years ago. Our findings potentially explain why the
      vast majority of SMS deletions and dup(17)(p11.2p11.2) occur at proximal and
      distal SMS-REPs and further support previous observations that higher-order
      genomic architecture involving LCRs arose recently during primate speciation and
      may predispose the human genome to both meiotic and mitotic rearrangements.

PMID- 11997340
TI  - Discovery of regulatory elements by a computational method for phylogenetic
      footprinting.
AB  - Phylogenetic footprinting is a method for the discovery of regulatory elements in
      a set of orthologous regulatory regions from multiple species. It does so by
      identifying the best conserved motifs in those orthologous regions. We describe a
      computer algorithm designed specifically for this purpose, making use of the
      phylogenetic relationships among the sequences under study to make more accurate
      predictions. The program is guaranteed to report all sets of motifs with the
      lowest parsimony scores, calculated with respect to the phylogenetic tree
      relating the input species. We report the results of this algorithm on several
      data sets of interest. A large number of known functional binding sites are
      identified by our method, but we also find several highly conserved motifs for
      which no function is yet known.

PMID- 11997341
TI  - Transcriptional regulation of the stem cell leukemia gene (SCL)--comparative
      analysis of five vertebrate SCL loci.
AB  - The stem cell leukemia (SCL) gene encodes a bHLH transcription factor with a
      pivotal role in hematopoiesis and vasculogenesis and a pattern of expression that
      is highly conserved between mammals and zebrafish. Here we report the isolation
      and characterization of the zebrafish SCL locus together with the identification
      of three neighboring genes, IER5, MAP17, and MUPP1. This region spans 68 kb and
      comprises the longest zebrafish genomic sequence currently available for
      comparison with mammalian, chicken, and pufferfish sequences. Our data show
      conserved synteny between zebrafish and mammalian SCL and MAP17 loci, thus
      suggesting the likely genomic domain necessary for the conserved pattern of SCL
      expression. Long-range comparative sequence analysis/phylogenetic footprinting
      was used to identify noncoding conserved sequences representing candidate
      transcriptional regulatory elements. The SCL promoter/enhancer, exon 1, and the
      poly(A) region were highly conserved, but no homology to other known mouse SCL
      enhancers was detected in the zebrafish sequence. A combined homology/structure
      analysis of the poly(A) region predicted consistent structural features,
      suggesting a conserved functional role in mRNA regulation. Analysis of the SCL
      promoter/enhancer revealed five motifs, which were conserved from zebrafish to
      mammals, and each of which is essential for the appropriate pattern or level of
      SCL transcription.

PMID- 11997342
TI  - Determination of redundancy and systems properties of the metabolic network of
      Helicobacter pylori using genome-scale extreme pathway analysis.
AB  - The capabilities of genome-scale metabolic networks can be described through the
      determination of a set of systemically independent and unique flux maps called
      extreme pathways. The first study of genome-scale extreme pathways for the
      simultaneous formation of all nonessential amino acids or ribonucleotides in
      Helicobacter pylori is presented. Three key results were obtained. First, the
      extreme pathways for the production of individual amino acids in H. pylori showed
      far fewer internal states per external state than previously found in Haemophilus
      influenzae, indicating a more rigid metabolic network. Second, the degree of
      pathway redundancy in H. pylori was essentially the same for the production of
      individual amino acids and linked amino acid sets, but was approximately twice
      that of the production of the ribonucleotides. Third, the metabolic network of H.
      pylori was unable to achieve extensive conversion of amino acids consumed to the
      set of either nonessential amino acids or ribonucleotides and thus diverted a
      large portion of its nitrogen to ammonia production, a potentially important
      result for pH regulation in its acidic habitat. Genome-scale extreme pathways
      elucidate emergent system-wide properties. Extreme pathway analysis is emerging
      as a potentially important method to analyze the link between the metabolic
      genotype and its phenotypes.

PMID- 11997343
TI  - Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be
      pseudogenes.
AB  - Only a minority of the genes, identified in the Caenorhabditis elegans genome
      sequence data by computer analysis, have been characterized experimentally. We
      attempted to determine the expression patterns for a random sample of the
      annotated genes using reporter gene fusions. A low success rate was obtained for
      evolutionarily recently duplicated genes. Analysis of the data suggests that this
      is not due to conditional or low-level expression. The remaining explanation is
      that most of the annotated genes in the recently duplicated category are
      pseudogenes, a proportion corresponding to 20% of all of the annotated C. elegans
      genes. Further support for this surprisingly high figure was sought by comparing
      sequences for families of recently duplicated C. elegans genes. Although only a
      preliminary analysis, clear evidence for a gene having been recently inactivated
      by genetic drift was found for many genes in the recently duplicated category. At
      least 4% of the annotated C. elegans genes can be recognized as pseudogenes
      simply from closer inspection of the sequence data. Lessons learned in
      identifying pseudogenes in C. elegans could be of value in the annotation of the
      genomes of other species where, although there may be fewer pseudogenes, they may
      be harder to detect.

PMID- 11997344
TI  - Analyses of the extent of shared synteny and conserved gene orders between the
      genome of Fugu rubripes and human 20q.
AB  - Cosmid and BAC contig maps have been constructed across two Fugu genomic regions
      containing the orthologs of human genes mapping to human chromosome 20q. Contig
      gene contents have been assessed by sample sequencing and comparative database
      analyses. Contigs are centered around two Fugu topoisomerase1 (top1) genes that
      were initially identified by sequence similarity to human TOP1 (20q12). Two other
      genes (SNAI1 and KRML) mapping to human chromosome 20 are also duplicated in
      Fugu. The two contigs have been mapped to separate Fugu chromosomes. Our data
      indicate that these linkage groups result from the duplication of an ancestral
      chromosome segment containing at least 40 genes that now map to the long arm of
      human chromosome 20. Although there is considerable conservation of synteny, gene
      orders are not well conserved between Fugu and human, with only very short
      sections of two to three adjacent genes being maintained in both organisms.
      Comparative analyses have allowed this duplication event to be dated before the
      separation of Fugu and zebrafish. Our data (which are best explained by regional
      duplication, followed by substantial gene loss) support the hypothesis that there
      have been a large number of gene and regional duplications (and corresponding
      gene loss) in the fish lineage, possibly resulting from a single whole genome
      duplication event.

PMID- 11997345
TI  - Large-scale protein annotation through gene ontology.
AB  - Recent progress in genomic sequencing, computational biology, and ontology
      development has presented an opportunity to investigate biological systems from a
      unique perspective, that is, examining genomes and transcriptomes through the
      multiple and hierarchical structure of Gene Ontology (GO). We report here our
      development of GO Engine, a computational platform for GO annotation, and
      analysis of the resultant GO annotations of human proteins. Protein annotation
      was centered on sequence homology with GO-annotated proteins and protein domain
      analysis. Text information analysis and a multiparameter cellular localization
      predictive tool were also used to increase the annotation accuracy, and to
      predict novel annotations. The majority of proteins corresponding to full-length
      mRNA in GenBank, and the majority of proteins in the NR database (nonredundant
      database of proteins) were annotated with one or more GO nodes in each of the
      three GO categories. The annotations of GenBank and SWISS-PROT proteins are
      available to the public at the GO Consortium web site.

PMID- 11997347
TI  - Protein coding palindromes are a unique but recurrent feature in Rickettsia.
AB  - Rickettsia are unique in inserting in-frame a number of palindromic sequences
      within protein coding regions. In this study, we extensively analyzed repeated
      sequences in the genome of Rickettsia conorii and examined their locations in
      regard to coding versus noncoding regions. We identified 656 interspersed
      repeated sequences classified into 10 distinct families. Of the 10 families,
      three palindromic sequence families showed clear cases of insertions into open
      reading frames (ORFs). The location of those in-frame insertions appears to be
      always compatible with the encoded protein three-dimensional (3-D) fold and
      function. We provide evidence for a progressive loss of the palindromic property
      over time after the insertions. This comprehensive study of Rickettsia repeats
      confirms and extends our previous observations and further indicates a
      significant role of selfish DNAs in the creation and modification of proteins.

PMID- 11997348
TI  - A fine physical map of the rice chromosome 4.
AB  - As part of an international effort to completely sequence the rice genome, we
      have produced a fine bacterial artificial chromosome (BAC)-based physical map of
      the Oryza sativa japonica Nipponbare chromosome 4 through an integration of 114
      sequenced BAC clones from a taxonomically related subspecies O. sativa indica
      Guangluai 4 and 182 RFLP and 407 expressed sequence tag (EST) markers with the
      fingerprinted data of the Nipponbare genome. The map consists of 11 contigs with
      a total length of 34.5 Mb covering 94% of the estimated chromosome size (36.8
      Mb). BAC clones corresponding to telomeres, as well as to the centromere
      position, were determined by BAC-pachytene chromosome fluorescence in situ
      hybridization (FISH). This gave rise to an estimated length ratio of 5.13 for the
      long arm and 2.9 for the short arm (on the basis of the physical map), which
      indicates that the short arm is a highly condensed one. The FISH analysis and
      physical mapping also showed that the short arm and the pericentromeric region of
      the long arm are rich in heterochromatin, which occupied 45% of the chromosome,
      indicating that this chromosome is likely very difficult to sequence. To our
      knowledge, this map provides the first example of a rapid and reliable physical
      mapping on the basis of the integration of the data from two taxonomically
      related subspecies.

PMID- 11997349
TI  - RePS: a sequence assembler that masks exact repeats identified from the shotgun
      data.
AB  - We describe a sequence assembler, RePS (repeat-masked Phrap with scaffolding),
      that explicitly identifies exact 20mer repeats from the shotgun data and removes
      them prior to the assembly. The established software is used to compute
      meaningful error probabilities for each base. Clone-end-pairing information is
      used to construct scaffolds that order and orient the contigs. We show with real
      data for human and rice that reasonable assemblies are possible even at coverages
      of only 4x to 6x, despite having up to 42.2% in exact repeats.

PMID- 11997346
TI  - Integration of Cot analysis, DNA cloning, and high-throughput sequencing
      facilitates genome characterization and gene discovery.
AB  - Cot-based sequence discovery represents a powerful means by which both low-copy
      and repetitive sequences can be selectively and efficiently fractionated, cloned,
      and characterized. Based upon the results of a Cot analysis, hydroxyapatite
      chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into
      highly repetitive (HR), moderately repetitive (MR), and single/low-copy (SL)
      sequence components that were consequently cloned to produce HRCot, MRCot, and
      SLCot genomic libraries. Filter hybridization (blotting) and sequence analysis
      both show that the HRCot library is enriched in sequences traditionally found in
      high-copy number (e.g., retroelements, rDNA, centromeric repeats), the SLCot
      library is enriched in low-copy sequences (e.g., genes and "nonrepetitive ESTs"),
      and the MRCot library contains sequences of moderate redundancy. The Cot analysis
      suggests that the sorghum genome is approximately 700 Mb (in agreement with
      previous estimates) and that HR, MR, and SL components comprise 15%, 41%, and 24%
      of sorghum DNA, respectively. Unlike previously described techniques to sequence
      the low-copy components of genomes, sequencing of Cot components is independent
      of expression and methylation patterns that vary widely among DNA elements,
      developmental stages, and taxa. High-throughput sequencing of Cot clones may be a
      means of "capturing" the sequence complexity of eukaryotic genomes at
      unprecedented efficiency.

PMID- 11997350
TI  - rVista for comparative sequence-based discovery of functional transcription
      factor binding sites.
AB  - Identifying transcriptional regulatory elements represents a significant
      challenge in annotating the genomes of higher vertebrates. We have developed a
      computational tool, rVista, for high-throughput discovery of cis-regulatory
      elements that combines clustering of predicted transcription factor binding sites
      (TFBSs) and the analysis of interspecies sequence conservation to maximize the
      identification of functional sites. To assess the ability of rVista to discover
      true positive TFBSs while minimizing the prediction of false positives, we
      analyzed the distribution of several TFBSs across 1 Mb of the well-annotated
      cytokine gene cluster (Hs5q31; Mm11). Because a large number of AP-1, NFAT, and
      GATA-3 sites have been experimentally identified in this interval, we focused our
      analysis on the distribution of all binding sites specific for these
      transcription factors. The exploitation of the orthologous human-mouse dataset
      resulted in the elimination of > 95% of the approximately 58,000 binding sites
      predicted on analysis of the human sequence alone, whereas it identified 88% of
      the experimentally verified binding sites in this region.

PMID- 11997351
TI  - Quality improvement guidelines for diagnostic infusion venography.

PMID- 11997352
TI  - Position statement: documenting physician experience for credentials for
      peripheral arterial procedures--what you need to know.

PMID- 11997353
TI  - The final outcome of primary infrainguinal percutaneous transluminal angioplasty
      in 100 consecutive patients with chronic critical limb ischemia.
AB  - PURPOSE: This study was performed to determine final outcomes in patients treated
      with infrainguinal percutaneous transluminal angioplasty (PTA) for chronic
      critical limb ischemia (CLI). MATERIALS AND METHODS: The study population
      consisted of 100 consecutive patients (mean age, 72 y; range, 38-90 y; 40 men and
      60 women) with 116 treated limbs. CLI was defined as rest pain or ischemic tissue
      defect combined with an ankle systolic pressure < or = 50 mm Hg. Indication for
      treatment was rest pain in 23 limbs (20%), ischemic ulcer in 50 (43%), and
      gangrene in 43 (37%). All patients were followed until they had met the study
      endpoints: major amputation or death. The mean follow-up period was 38 months (1
      119 mo). Limb salvage, survival, and life with limb rates were determined along
      with their determinants. RESULTS: On average, 1.9 invasive procedures were
      required during the lifespan of a critically ischemic limb, including primary PTA
      and 32 repeat PTA procedures, 11 surgical revascularizations, and 51 amputations.
      The major amputation rate was 32% (n = 37). Limb salvage for endovascular
      treatments at 3, 5, and 8 years was 65%, 60%, and 60%, respectively (SE of
      estimate [SEE] <or = 0.06), and the corresponding life with limb rates were 29%,
      18%, and 6% (SEE < or = 0.05). A greater number of diseased vessels in the
      treated limb was associated with poorer limb salvage (P =.004). Survival rates
      were 41%, 26%, and 14% (SEE < or = 0.05) at 3, 5, and 10 years. The 10-year
      survival rate was markedly poorer than that in the age- and sex-matched control
      population. Coronary artery disease (P =.001) and poor peripheral runoff (P =.02)
      were associated with decreased survival. CONCLUSIONS: Infrainguinal PTA in
      patients with CLI results in acceptable limb salvage with a low number of
      additional revascularization treatments, but patient survival is poor.

PMID- 11997354
TI  - Endovascular placement of a nitinol-ePTFE stent-graft for abdominal aortic
      aneurysms: initial and midterm results.
AB  - PURPOSE: Because first-generation stent-grafts did not meet initial expectations,
      a recently designed nitinol-expanded polytetrafluoroethylene (ePTFE) stent-graft
      was tested for treatment of abdominal aortic aneurysms (AAAs) in a prospective
      clinical study. The primary study endpoints were technical success and safety.
      MATERIALS AND METHODS: A nitinol-ePTFE self-expandable stent-graft (Excluder) was
      used to treat 72 patients with AAAs. The median follow-up period was 21.5 months
      +/- 13 (range, 1-46 mo). RESULTS: Primary technical success in accurate placement
      of the device was achieved in 70 of 72 patients (97%). Complete exclusion of the
      aneurysm from arterial flow was achieved in 57 of 72 patients (79.2%). Three type
      I leaks were observed during implantation and were immediately corrected with a
      proximal cuff prosthesis in two patients. Fourteen of 72 patients (19.4%) had a
      type II leak. Major complications were observed in three patients (4.1%),
      including one death in the early postinterventional period (one of 72, 1.4%). At
      3 months, aneurysms were excluded in 70 of 71 patients (98.6%), and at 12 months,
      aneurysms were occluded in 29 of 30 patients (96.7%). The maximum diameter of the
      aneurysm decreased from 55 mm +/- 11 (median +/- SD) before intervention to 53 mm
      +/- 13 at 6 and 12 months. None of the patients showed aneurysm growth.
      CONCLUSION: This newly designed stent-graft proved to be effective and safe for
      treatment of AAAs.

PMID- 11997355
TI  - Craniofacial cavernous venous malformations: percutaneous sclerotherapy with use
      of ethanolamine oleate.
AB  - PURPOSE: To assess the efficacy of percutaneous sclerotherapy with use of
      ethanolamine oleate for craniofacial cavernous venous malformations. MATERIALS
      AND METHODS: From 1991 to 2001, sclerotherapy (average of two procedures per
      patient) was performed in 29 patients (mean age, 22 y; 10 male) with craniofacial
      venous malformations. Direct puncture venography was performed with use of water
      soluble contrast media to delineate the extent of the lesions. CO(2) gas was used
      as contrast medium in addition to water-soluble contrast media in five patients
      in whom lesions had large nondependent areas. Coil embolization with a
      transvenous approach was performed in two patients when the lesions had large
      draining veins. Then, a mixture of 5% ethanolamine oleate and iodized oil (ratio,
      5:1-5:2) was injected manually into the lesions under fluoroscopic guidance to
      monitor the process. A total of 59 procedures were performed. Clinical follow-up
      was obtained in 25 of 29 patients. The duration of follow-up ranged from 10 days
      to 6 years (mean, 8.5 mo). The effectiveness of sclerotherapy was assessed on the
      basis of clinical, surgical, and radiologic findings. RESULTS: The procedures
      were effective in 14 of 16 patients who underwent sclerotherapy only. The
      procedures were beneficial for all nine patients who underwent sclerotherapy and
      surgery. There was no skin injury or nerve damage. The trismus that appeared in
      two patients with lesions in the masticator space was treated well by
      conservative therapy. CONCLUSION: Percutaneous sclerotherapy with use of
      ethanolamine oleate is a safe and effective treatment of craniofacial cavernous
      venous malformations. However, renal function was not specifically evaluated
      after treatment, and therefore occult renal dysfunction cannot be excluded.

PMID- 11997356
TI  - Evaluation of vascular and interventional procedures with time-action analysis: a
      pilot study.
AB  - PURPOSE: To provide an objective method to measure the efficiency of vascular and
      interventional procedures. MATERIALS AND METHODS: The time-action analysis method
      is defined for peripheral vascular and interventional procedures. A taxonomy of
      actions is defined, geared specifically toward these procedures. The actions are:
      start-up/wrap-up, exchange, navigate, image, diagnose, treat, handle material,
      wait, compress puncture site, and unclassified. The recording method and analysis
      techniques are described. To show the type of data that can be obtained, the time
      action analysis of 30 procedures is presented. RESULTS: The results provide a
      detailed picture of the time spent on various actions. Of all actions, the most
      time is spent on compressing the puncture site (18.5%), whereas the highest
      frequency of actions are for exchange of catheters, guide wires, and sheaths
      (20.4 times per procedure). Radiation exposure can be analyzed in detail, which
      can yield directions for possible reduction. For instance, 5.2%-8.3% of the total
      radiation exposure occurs during preparation of imaging to adjust the position of
      the patient table and set the image intensifier diaphragm. CONCLUSION: Time
      action analysis provides an objective measurement method to monitor and evaluate
      vascular and interventional procedures. Potential applications and limitations of
      the technique are discussed.

PMID- 11997357
TI  - Comparison of small intestinal submucosa-covered and noncovered nitinol stents in
      sheep iliac arteries: a pilot study.
AB  - PURPOSE: To compare the biocompatibility and performance of nitinol endografts
      covered externally or internally with small intestinal submucosa (SIS) with bare
      nitinol stents in medium-sized arteries. MATERIALS AND METHODS: Eighteen nitinol
      Zilver stents were used: six externally SIS-covered endografts (ECEs), six
      internally SIS-covered endografts (ICEs), and six bare stents (BSs). Devices were
      implanted in the balloon-injured external iliac arteries (EIAs) of nine female
      sheep via carotid approach. Arteriograms were obtained before and after
      implantation and before animal sacrifice at 1, 3, and 6 months. Histologic
      studies of explanted specimens were performed. RESULTS: Implantation of all BSs,
      ECEs, and ICEs was successful, but slight luminal narrowing of 19% +/- 5.3%
      (range, 12%-28%) was seen in ICEs on postimplantation angiograms. At sacrifice,
      all six BSs and ECEs were patent, with BSs showing a mean angiographic luminal
      narrowing of 8.4% +/- 7.2% (range, 0%-18%) and ECEs showing a mean angiographic
      luminal narrowing of 16% +/- 7.5% (range, 6.5%-26%) as a result of neointimal
      hyperplasia. Four ICEs showed luminal narrowing of 21% +/- 17% (range, 0%-35%) as
      a result of marked neointimal hyperplasia and two were occluded, one at 3 months
      and the other at 6 months. ECEs and BSs showed approximately 80% lumen
      endothelialization at 1 month, which increased to 100% at 3 and 6 months. ICEs
      did not show complete endothelialization. CONCLUSION: The BS had the least vessel
      wall reaction. ECEs exhibited early endothelialization with early mild to
      moderate wall reaction decreasing at the late study stages. ICEs showed extensive
      wall reaction, possibly as a result of technical problems with SIS attachment.

PMID- 11997358
TI  - Radial force and wall apposition of balloon-expandable vascular stents in
      eccentric stenoses: an in vitro evaluation in a curved vessel model.
AB  - PURPOSE: Important criteria for optimized stent implantation are high radial
      force and complete apposition of the stent itself. The aim of this study was to
      develop a simple method to assess these parameters under controlled experimental
      conditions and to compare vascular stents of different designs with regard to
      these parameters. MATERIALS AND METHODS: Five balloon-expandable stents of
      different designs (Jostent Flex, MAC stent, ML-Tristar, ML-Ultra, and S670) were
      tested. Fourteen stents of each type were implanted in a curved plastic vessel
      model (curve radius, 10 mm; lumen diameter, 3.5 mm) with use of a balloon
      inflation pressure of 12 atm. Part of the model was a nonflexible eccentric
      stenosis which was 2 mm or 8 mm in length. After stent implantation, a stenosis
      of 10%-70% was induced and radial force of the stent struts was measured at the
      site of the stenosis. The apposition of the stent to the vessel wall was imaged
      by high-resolution radiography. RESULTS: Analysis of variance showed significant
      differences of radial force between the tested stents (P <.001). The ML-Tristar
      and ML-Ultra stents had the highest radial force with maximum mean values of 687
      cN and 846 cN at a stenosis of 70% in the model with the long stenosis. The
      radial force of the S670 stent was the lowest whereas the MAC stents showed an
      intermediate radial force. Radial force of the ML-Ultra stent was as much as 3.8
      times higher than the force of the S670 stent (P <.001). Fifty percent of the ML
      Tristar and ML-Ultra stents did not expand sufficiently to touch the vessel
      surface at the outer curvature. With an inflation pressure of 17 atm, complete
      apposition of these stents was achieved. The highest number of apposition
      irregularities was found in the S670 group (13 of 14 stents), whereas the MAC
      stents revealed the lowest number of irregular appositions (three of 14 stents).
      A significant correlation was found between the number of interconnecting struts
      and the number of irregular apposition events (P <.01). CONCLUSIONS: This model
      allows an accurate in vitro evaluation of different stent parameters, such as
      apposition to the vessel wall and radial force. None of the investigated stents
      showed optimal results with respect to both parameters. The apposition behavior
      was significantly influenced by the architecture of the stents.

PMID- 11997359
TI  - Repeated Gunther Tulip inferior vena cava filter repositioning to prolong
      implantation time.
AB  - A patient presented with iliofemoral deep vein thrombosis, a small pulmonary
      embolism, and a paradoxic embolus to the axillary artery resulting from a patent
      foramen ovale (PFO). As prophylaxis against further paradoxic emboli while
      awaiting percutaneous PFO closure, a Gunther Tulip inferior vena cava (IVC)
      filter was implanted. To prevent incorporation of the IVC filter into the caval
      wall, it was repositioned twice with use of a filter retrieval set from a
      transjugular approach. In this way, the implantation time of the filter was
      extended beyond the recommended period of 10 days. The filter was successfully
      retrieved 19 days later during percutaneous closure of the PFO.

PMID- 11997360
TI  - Treatment of pelvic arteriovenous malformations with ethylene vinyl alcohol
      copolymer (Onyx).
AB  - In this article, two successful embolizations of large pelvic arteriovenous
      malformations (AVMs) with use of ethylene vinyl alcohol, a radiopaque,
      nonadhesive liquid casting agent, are reported. Both patients presented with
      large symptomatic pelvic AVMs requiring therapy. Coaxial microcatheter techniques
      were used to achieve complete success in one case and partial success in the
      other. Clinical success has been maintained in both patients at 2-year follow-up.

PMID- 11997361
TI  - Percutaneous pediculoplasty: polymethylmethacrylate injection into lytic
      vertebral pedicle lesions.
AB  - Two patients with painful lytic lesions of the vertebral pedicle were treated
      with percutaneous pediculoplasty. This technique, similar to vertebroplasty but
      with increased procedural risks because of the immediate vicinity of neural
      structures, was performed under high-quality biplane fluoroscopic guidance. For
      lesions involving both the pedicle and the vertebral body, a double-needle
      unipedicular technique is advocated.

PMID- 11997362
TI  - Intravascular ultrasound in the diagnosis and treatment of iliac vein compression
      (May-Thurner) syndrome.
AB  - Intravascular ultrasound (IVUS) imaging and venography of the left common femoral
      and iliac veins were performed in 16 patients. The studies were evaluated for the
      anatomic cause of obstruction and how IVUS influenced endovascular management.
      IVUS demonstrated the cause of vessel compression in all 16 patients. Other
      findings, such as associated thrombus and guide wire localization within the
      residual vessel lumen, can modify the approach to intervention in as many as 50%
      of patients. IVUS is a useful adjunct in the diagnosis and endovascular
      management of iliac vein compression syndrome.

PMID- 11997363
TI  - SCVIR 2002 Film Panel case 1: vasculitis associated with lymphoproliferative
      disease.

PMID- 11997364
TI  - SCVIR 2002 Film Panel case 2: TIPS for bleeding varices in cystic fibrosis and
      liver cirrhosis.

PMID- 11997365
TI  - SCVIR 2002 Film Panel case 3: aortic occlusion secondary to intimal sarcoma.

PMID- 11997366
TI  - SCVIR 2002 Film Panel case 4: massive intraperitoneal hemorrhage caused by
      peliosis hepatis.

PMID- 11997367
TI  - Re: Use of aortic cuffs to exclude iliac artery aneurysms during AneuRx stent
      graft placement: initial experience.

PMID- 11997368
TI  - Restenosis and pseudoaneurysm formation after stent placement for aortic
      coarctation in Williams syndrome.

PMID- 11997369
TI  - Re: Nonlocalized lower gastrointestinal bleeding: provocative bleeding studies
      with intraarterial tPA, heparin, and tolazoline.

PMID- 11997370
TI  - Proceedings of the Antioxidants and Reactive Oxygen Species in Plants Session of
      the Annual Meeting of the Society for Experimental Biology. Canterbury, United
      Kingdom, April 2-3, 2001.

PMID- 11997371
TI  - Signal transduction during oxidative stress.
AB  - As an unfortunate consequence of aerobic life, active oxygen species (AOS) are
      formed by partial reduction of molecular oxygen. Plants possess a complex battery
      of enzymatic and non-enzymatic antioxidants that can protect cells from oxidative
      damage by scavenging AOS. It is becoming evident that AOS, which are generated
      during pathogen attack and abiotic stress situations, are recognized by plants as
      a signal for triggering defence responses. An overview of the literature is
      presented on the signalling role of AOS in plant defence responses, cell death,
      and development. Special attention is given to AOS and redox-regulated gene
      expression and the role of kinases and phosphatases in redox signal transduction.

PMID- 11997372
TI  - Hydrogen peroxide and nitric oxide as signalling molecules in plants.
AB  - It is now clear that hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) function
      as signalling molecules in plants. A wide range of abiotic and biotic stresses
      results in H(2)O(2) generation, from a variety of sources. H(2)O(2) is removed
      from cells via a number of antioxidant mechanisms, both enzymatic and non
      enzymatic. Both biotic and abiotic stresses can induce NO synthesis, but the
      biosynthetic origins of NO in plants have not yet been resolved. Cellular
      responses to H(2)O(2) and NO are complex, with considerable cross-talk between
      responses to several stimuli. In this review the potential roles of H(2)O(2) and
      NO during various stresses and the signalling pathways they activate are
      discussed. Key signalling components that might provide targets for enhancing
      crop production are also identified.

PMID- 11997373
TI  - Imaging of photo-oxidative stress responses in leaves.
AB  - High resolution digital imaging was used to identify sites of photo-oxidative
      stress responses in Arabidopsis leaves non-invasively, and to demonstrate the
      potential of using a suite of imaging techniques for the study of oxidative
      metabolism in planta. Tissue-specific photoinhibition of photosynthesis in
      individual chloroplasts in leaves was imaged by chlorophyll fluorescence
      microscopy. Singlet oxygen production was assessed by imaging the quenching of
      the fluorescence of dansyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole (DanePy)
      that results from its reaction with singlet oxygen. Superoxide and hydrogen
      peroxide accumulation were visualized by the reduction of nitroblue tetrazolium
      (NBT) to formazan deposits and by polymerization with 3,3'-diaminobenzidine
      (DAB), respectively. Stress-induced expression of a gene involved with
      antioxidant metabolism was imaged from the bioluminescence from leaves of an
      Arabidopsis APX2-LUC transformant, which co-expresses an ascorbate peroxidase
      (APX2) with firefly luciferase. Singlet oxygen and superoxide production were
      found to be primarily located in mesophyll tissues whereas hydrogen peroxide
      accumulation and APX2 gene expression were primarily localized in the vascular
      tissues.

PMID- 11997374
TI  - Reactive oxygen species, antioxidant systems and nitric oxide in peroxisomes.
AB  - Peroxisomes are subcellular organelles with an essentially oxidative type of
      metabolism. Like chloroplasts and mitochondria, plant peroxisomes also produce
      superoxide radicals (O2*(-)) and there are, at least, two sites of superoxide
      generation: one in the organelle matrix, the generating system being xanthine
      oxidase, and another site in the peroxisomal membranes dependent on NAD(P)H. In
      peroxisomal membranes, three integral polypeptides (PMPs) with molecular masses
      of 18, 29 and 32 kDa have been shown to generate radicals O2*(-). Besides
      catalase, several antioxidative systems have been demonstrated in plant
      peroxisomes, including different superoxide dismutases, the ascorbate-glutathione
      cycle, and three NADP-dependent dehydrogenases. A CuZn-SOD and two Mn-SODs have
      been purified and characterized from different types of peroxisomes. The four
      enzymes of the ascorbate-glutathione cycle (ascorbate peroxidase,
      monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione
      reductase) as well as the antioxidants glutathione and ascorbate have been found
      in plant peroxisomes. The recycling of NADPH from NADP(+) can be carried out in
      peroxisomes by three dehydrogenases: glucose-6-phosphate dehydrogenase, 6
      phosphogluconate dehydrogenase, and isocitrate dehydrogenase. In the last decade,
      different experimental evidence has suggested the existence of cellular functions
      for peroxisomes related to reactive oxygen species (ROS), but the recent
      demonstration of the presence of nitric oxide synthase (NOS) in plant peroxisomes
      implies that these organelles could also have a function in plant cells as a
      source of signal molecules like nitric oxide (NO*), superoxide radicals, hydrogen
      peroxide, and possibly S-nitrosoglutathione (GSNO).

PMID- 11997375
TI  - Active oxygen and cell death in cereal aleurone cells.
AB  - The cereal aleurone layer is a secretory tissue whose function is regulated by
      gibberellic acid (GA) and abscisic acid (ABA). Aleurone cells lack functional
      chloroplasts, thus excluding photosynthesis as a source of active oxygen species
      (AOS) in cell death. Incubation of barley aleurone layers or protoplasts in GA
      initiated the cell death programme, but incubation in ABA delays programmed cell
      death (PCD). Light, especially blue and UV-A light, and H(2)O(2) accelerate PCD
      of GA-treated aleurone cells, but ABA-treated aleurone cells are refractory to
      light and H(2)O(2) and are not killed. It was shown that light elevated
      intracellular H(2)O(2), and that the rise in H(2)O(2) was greater in GA-treated
      cells compared to cells in ABA. Experiments with antioxidants show that PCD in
      aleurone is probably regulated by AOS. The sensitivity of GA-treated aleurone to
      light and H(2)O(2) is a result of lowered amounts of enzymes that metabolize AOS.
      mRNAs encoding catalase, ascorbate peroxidase and superoxide dismutase are all
      reduced during 6-18 h of incubation in GA, but these mRNAs were present in higher
      amounts in cells incubated in ABA. The amounts of protein and enzyme activities
      encoded by these mRNAs were also dramatically reduced in GA-treated cells.
      Aleurone cells store and metabolize neutral lipids via the glyoxylate cycle in
      response to GA, and glyoxysomes are one potential source of AOS in the GA-treated
      cells. Mitochondria are another potential source of AOS in GA-treated cells. AOS
      generated by these organelles bring about membrane rupture and cell death.

PMID- 11997376
TI  - Interactions between biosynthesis, compartmentation and transport in the control
      of glutathione homeostasis and signalling.
AB  - Glutathione has numerous roles in cellular defence and in sulphur metabolism.
      These functions depend or impact on the concentration and/or redox state of leaf
      glutathione pools. Effective function requires homeostatic control of
      concentration and redox state, with departures from homeostasis acting as signals
      that trigger adaptive responses. Intercellular and intracellular glutathione
      pools are linked by transport across membranes. It is shown that glutathione can
      cross the chloroplast envelope at rates similar to the speed of biosynthesis.
      Control of glutathione concentration and redox state is therefore due to a
      complex interplay between biosynthesis, utilization, degradation,
      oxidation/reduction, and transport. All these factors must be considered in order
      to evaluate the significance of glutathione as a signalling component during
      development, abiotic stress, or pathogen attack.

PMID- 11997377
TI  - Regulation and function of ascorbate peroxidase isoenzymes.
AB  - Even under optimal conditions, many metabolic processes, including the
      chloroplastic, mitochondrial, and plasma membrane-linked electron transport
      systems of higher plants, produce active oxygen species (AOS). Furthermore, the
      imposition of biotic and abiotic stress conditions can give rise to excess
      concentrations of AOS, resulting in oxidative damage at the cellular level.
      Therefore, antioxidants and antioxidant enzymes function to interrupt the
      cascades of uncontrolled oxidation in each organelle. Ascorbate peroxidase (APX)
      exists as isoenzymes and plays an important role in the metabolism of H(2)O(2) in
      higher plants. APX is also found in eukaryotic algae. The characterization of APX
      isoenzymes and the sequence analysis of their clones have led to a number of
      investigations that have yielded interesting and novel information on these
      enzymes. Interestingly, APX isoenzymes of chloroplasts in higher plants are
      encoded by only one gene, and their mRNAs are generated by alternative splicing
      of the gene's two 3'-terminal exons. Manipulation of the expression of the
      enzymes involved in the AOS-scavenging systems by gene-transfer technology has
      provided a powerful tool for increasing the present understanding of the
      potential of the defence network against oxidative damage caused by environmental
      stresses. Transgenic plants expressing E. coli catalase to chloroplasts with
      increased tolerance to oxidative stress indicate that AOS-scavenging enzymes,
      especially chloroplastic APX isoenzymes are sensitive under oxidative stress
      conditions. It is clear that a high level of endogenous ascorbate is essential
      effectively to maintain the antioxidant system that protects plants from
      oxidative damage due to biotic and abiotic stresses.

PMID- 11997378
TI  - The function of the chloroplast 2-cysteine peroxiredoxin in peroxide
      detoxification and its regulation.
AB  - The Arabidopsis genome contains nine open reading frames with homology to members
      of the peroxiredoxin (prx) family: one 1-Cys-prx, two 2-Cys-prx, five type II
      prx, and one peroxiredoxin Q. The function of the peroxiredoxins in plant
      metabolism is only slowly emerging. They are assumed to reduce toxic peroxides to
      their corresponding alcohols with a rather broad substrate specificity. The 2-Cys
      peroxiredoxins (2-CP) were recently identified as members of the antioxidant
      defence system of chloroplasts. Knock-out mutants of Synechocystis and antisense
      mutants of Arabidopsis have provided insight into the function of 2-CPs in the
      photosynthetic antioxidant network. This review summarizes present knowledge on
      the enzymatic mechanism, the physiological context and the genetic regulation of
      the 2-CPs in plants and cyanobacteria. In addition, an extrapolation on the
      metabolic role of the chloroplast 2-CP is attempted based on the molecular
      features of 2-CPs from other organisms.

PMID- 11997379
TI  - Role of superoxide dismutases (SODs) in controlling oxidative stress in plants.
AB  - Reactive O(2) species (ROS) are produced in both unstressed and stressed cells.
      Plants have well-developed defence systems against ROS, involving both limiting
      the formation of ROS as well as instituting its removal. Under unstressed
      conditions, the formation and removal of O(2) are in balance. However, the
      defence system, when presented with increased ROS formation under stress
      conditions, can be overwhelmed. Within a cell, the superoxide dismutases (SODs)
      constitute the first line of defence against ROS. Specialization of function
      among the SODs may be due to a combination of the influence of subcellular
      location of the enzyme and upstream sequences in the genomic sequence. The
      commonality of elements in the upstream sequences of Fe, Mn and Cu/Zn SODs
      suggests a relatively recent origin for those regulatory regions. The differences
      in the upstream regions of the three FeSOD genes suggest differing regulatory
      control which is borne out in the research literature. The finding that the
      upstream sequences of Mn and peroxisomal Cu/Zn SODs have three common elements
      suggests a common regulatory pathway. The tools are available to dissect further
      the molecular basis for antioxidant defence responses in plant cells. SODs are
      clearly among the most important of those defences, when coupled with the
      necessary downstream events for full detoxification of ROS.

PMID- 11997380
TI  - Pyramiding Mn-superoxide dismutase transgenes to improve persistence and biomass
      production in alfalfa.
AB  - Expression of individual superoxide dismutase (SOD) transgenes improves
      environmental stress tolerance and biomass production in alfalfa (Medicago sativa
      L.). The objective of this study was to test the hypothesis that synergy exists
      between transgenic SOD stress-tolerance mechanisms, specifically that the
      simultaneous expression of two SOD transgenes confers greater benefit than the
      expression of a single SOD transgene. The hypothesis was tested through an
      evaluation of an F(1) family generated through a sexual cross of a hemizygous Mit
      MnSOD plant and a hemizygous Chl-MnSOD-transgenic alfalfa plant which had
      previously been screened in field trials for improved persistence. Southern
      analyses revealed that the parents each had single insertion regions of the MnSOD
      cDNA and the inheritance followed the expected Mendelian ratios. Native PAGE gels
      and enzyme inhibition assays revealed the activity of the transgenic MnSOD
      isozymes. F(1) progeny containing either the Mit-MnSOD or the Chl-MnSOD transgene
      had significantly higher storage organ (crown+root) biomass compared to non
      transgenic siblings. The joint expression of the transgenes resulted in a
      numerical increase in total SOD activity. However, F(1) progeny containing both
      transgenes had lower shoot and storage organ biomass compared to siblings having
      only one or the other transgene, a result that did not support the authors'
      hypothesis. It was postulated that a promoter with lower expression than 35S may
      be necessary if closely related transgenes are to be pyramided in the same plant.

PMID- 11997381
TI  - Plant responses to abiotic stresses: heavy metal-induced oxidative stress and
      protection by mycorrhization.
AB  - The aim of this review is to assess the mode of action and role of antioxidants
      as protection from heavy metal stress in roots, mycorrhizal fungi and
      mycorrhizae. Based on their chemical and physical properties three different
      molecular mechanisms of heavy metal toxicity can be distinguished: (a) production
      of reactive oxygen species by autoxidation and Fenton reaction; this reaction is
      typical for transition metals such as iron or copper, (b) blocking of essential
      functional groups in biomolecules, this reaction has mainly been reported for non
      redox-reactive heavy metals such as cadmium and mercury, (c) displacement of
      essential metal ions from biomolecules; the latter reaction occurs with different
      kinds of heavy metals. Transition metals cause oxidative injury in plant tissue,
      but a literature survey did not provide evidence that this stress could be
      alleviated by increased levels of antioxidative systems. The reason may be that
      transition metals initiate hydroxyl radical production, which can not be
      controlled by antioxidants. Exposure of plants to non-redox reactive metals also
      resulted in oxidative stress as indicated by lipid peroxidation, H(2)O(2)
      accumulation, and an oxidative burst. Cadmium and some other metals caused a
      transient depletion of GSH and an inhibition of antioxidative enzymes, especially
      of glutathione reductase. Assessment of antioxidative capacities by metabolic
      modelling suggested that the reported diminution of antioxidants was sufficient
      to cause H(2)O(2) accumulation. The depletion of GSH is apparently a critical
      step in cadmium sensitivity since plants with improved capacities for GSH
      synthesis displayed higher Cd tolerance. Available data suggest that cadmium,
      when not detoxified rapidly enough, may trigger, via the disturbance of the redox
      control of the cell, a sequence of reactions leading to growth inhibition,
      stimulation of secondary metabolism, lignification, and finally cell death. This
      view is in contrast to the idea that cadmium results in unspecific necrosis.
      Plants in certain mycorrhizal associations are less sensitive to cadmium stress
      than non-mycorrhizal plants. Data about antioxidative systems in mycorrhizal
      fungi in pure culture and in symbiosis are scarce. The present results indicate
      that mycorrhization stimulated the phenolic defence system in the Paxillus-Pinus
      mycorrhizal symbiosis. Cadmium-induced changes in mycorrhizal roots were absent
      or smaller than those in non-mycorrhizal roots. These observations suggest that
      although changes in rhizospheric conditions were perceived by the root part of
      the symbiosis, the typical Cd-induced stress responses of phenolics were
      buffered. It is not known whether mycorrhization protected roots from Cd-induced
      injury by preventing access of cadmium to sensitive extra- or intracellular
      sites, or by excreted or intrinsic metal-chelators, or by other defence systems.
      It is possible that mycorrhizal fungi provide protection via GSH since higher
      concentrations of this thiol were found in pure cultures of the fungi than in
      bare roots. The development of stress-tolerant plant-mycorrhizal associations may
      be a promising new strategy for phytoremediation and soil amelioration measures.

PMID- 11997382
TI  - The apoplastic oxidative burst in response to biotic stress in plants: a three
      component system.
AB  - The oxidative burst, the generation of reactive oxygen species (ROS) in response
      to microbial pathogen attack, is a ubiquitous early part of the resistance
      mechanisms of plant cells. It has also become apparent from the study of a number
      of plant-pathogen interactions and those modelled by elicitor treatment of
      cultured cells that there may be more than one mechanism operating. However, one
      mechanism may be dominant in any given species. NADPH oxidases have been
      implicated in a number of systems and have been cloned and characterized.
      However, the enzyme system which is the major source of ROS in French bean
      (Phaseolus vulgaris) cells treated with a cell wall elicitor from Colletotrichum
      lindemuthianum, appears to be dependent on an exocellular peroxidase. The second
      component, the extracellular alkalinization, occurs as a result of the Ca(2+) and
      proton influxes and the K(+) efflux common to most elicitation systems as one of
      the earliest responses. The third component, the actual reductant/substrate, has
      remained elusive. The low molecular weight compound composition of apoplastic
      fluid was compared before and after elicitation. The substrate only becomes
      available some min after elicitation and can be extracted, so that by comparing
      the profiles by LC-MS it has been possible to identify possible substrates. The
      mechanism has proved to be complex and may involve a number of low molecular
      weight components. Stimulation of H(2)O(2) production was observed with saturated
      fatty acids such as palmitate and stearate without concomitant oxylipin
      production. This biochemical evidence is supported by immunolocalization studies
      on papillae forming at bacterial infection sites that show the peroxidase isoform
      present at sites of H(2)O(2) production revealed by cerium chloride staining
      together with the cross-linked wall proteins and callose and callose synthase.
      The peroxidase has been cloned and expressed in Pichia pastoris and has been
      shown to catalyse the oxidation reaction with the same kinetics as the purified
      enzyme. Furthermore, Arabidopsis plants transformed heterologously using the
      French bean peroxidase in antisense orientation have proved to be highly
      susceptible to bacterial and fungal pathogens. Thus it is possible that
      Arabidopsis is another species with the potential to mount an apoplastic
      oxidative burst and these transformed plant lines may be useful to identify the
      peroxidase that is responsible.

PMID- 11997383
TI  - AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle
      through down-regulated mammalian target of rapamycin (mTOR) signaling.
AB  - AMP-activated protein kinase (AMPK) is viewed as an energy sensor that acts to
      modulate glucose uptake and fatty acid oxidation in skeletal muscle. Given that
      protein synthesis is a high energy-consuming process, it may be transiently
      depressed during cellular energy stress. Thus, the intent of this investigation
      was to examine whether AMPK activation modulates the translational control of
      protein synthesis in skeletal muscle. Injections of 5-aminoimidazole-4
      carboxamide 1-beta-d-ribonucleoside (AICAR) were used to activate AMPK in male
      rats. The activity of alpha1 AMPK remained unchanged in gastrocnemius muscle from
      AICAR-treated animals compared with controls, whereas alpha2 AMPK activity was
      significantly increased (51%). AICAR treatment resulted in a reduction in protein
      synthesis to 45% of the control value. This depression was associated with
      decreased activation of protein kinases in the mammalian target of rapamycin
      (mTOR) signal transduction pathway as evidenced by reduced phosphorylation of
      protein kinase B on Ser(473), mTOR on Ser(2448), ribosomal protein S6 kinase on
      Thr(389), and eukaryotic initiation factor eIF4E-binding protein on Thr(37). A
      reduction in eIF4E associated with eIF4G to 10% of the control value was also
      noted. In contrast, eIF2B activity remained unchanged in response to AICAR
      treatment and therefore would not appear to contribute to the depression in
      protein synthesis. This is the first investigation to demonstrate changes in
      translation initiation and skeletal muscle protein synthesis in response to AMPK
      activation.

PMID- 11997384
TI  - N-acetylcysteine and celecoxib lessen cadmium cytotoxicity which is associated
      with cyclooxygenase-2 up-regulation in mouse neuronal cells.
AB  - In many neurodegenerative disorders, aggregates of ubiquitinated proteins are
      detected in neuronal inclusions, but their role in neurodegeneration remains to
      be defined. To identify intracellular mechanisms associated with the appearance
      of ubiquitin-protein aggregates, mouse neuronal HT4 cells were treated with
      cadmium. This heavy metal is a potent cell poison that mediates oxidative stress
      and disrupts the ubiquitin/proteasome pathway. In the current studies, the
      following intracellular events were found to be also induced by cadmium: (i) a
      specific rise in cyclooxygenase-2 (COX-2) gene expression but not COX-1; (ii) an
      increase in the extracellular levels of the proinflammatory prostaglandin E2, a
      product of COX-2; and (iii) production of 4-hydroxy-2-nonenal-protein adducts,
      which result from lipid peroxidation. In addition, cadmium treatment led to the
      accumulation of high molecular weight ubiquitin-COX-2 conjugates and perturbed
      COX-2 glycosylation. The thiol-reducing antioxidant N-acetylcysteine, and, to a
      lesser extent, the COX-2 inhibitor celecoxib, attenuated the loss of cell
      viability induced by cadmium demonstrating that oxidative stress and COX-2
      activation contribute to cadmium cytotoxicity. These findings establish that
      disruption of the ubiquitin/proteasome pathway is not the only event triggered by
      cadmium. This oxidative stressor also activates COX-2 function. Both events could
      be triggered by formation of 4-hydroxy-2-nonenal as a result of cadmium-induced
      lipid peroxidation. Proinflammatory responses stimulated by oxidative stressors
      that mimic the cadmium effects may, therefore, be important initiators of the
      neurodegenerative process and exacerbate its progress.

PMID- 11997385
TI  - Role of fruA and csgA genes in gene expression during development of Myxococcus
      xanthus. Analysis by two-dimensional gel electrophoresis.
AB  - Two genes, fruA and csgA, encoding a putative transcription factor and C-factor,
      respectively, are essential for fruiting body formation of Myxococcus xanthus. To
      investigate the role of fruA and csgA genes in developmental gene expression,
      developing cells as well as vegetative cells of M. xanthus wild-type, fruA::Tc,
      and csgA731 strains were pulse-labeled with [(35)S]methionine, and the whole cell
      proteins were analyzed using two-dimensional immobilized pH gradient/SDS-PAGE.
      Differences in protein synthesis patterns among more than 700 protein spots were
      detected during development of the three strains. Fourteen proteins showing
      distinctly different expression patterns in mutant cells were analyzed in more
      detail. Five of the 14 proteins were identified as elongation factor Tu (EF-Tu),
      Dru, DofA, FruA, and protein S by immunoblot analysis and mass spectroscopy. A
      gene encoding DofA was cloned and sequenced. Although both fruA and csgA genes
      regulate early development of M. xanthus, they were found to differently regulate
      expression of several developmental genes. The production of six proteins,
      including DofA and protein S, was dependent on fruA, whereas the production of
      two proteins was dependent on csgA, and one protein was dependent on both fruA
      and csgA. To explain the present findings, a new model was presented in which
      different levels of FruA phosphorylation may distinctively regulate the
      expression of two groups of developmental genes.

PMID- 11997386
TI  - Development of platelet inhibition by cAMP during megakaryocytopoiesis.
AB  - Prostacyclin is a potent inhibitor of agonist-induced Ca2+ increases in
      platelets, but in the megakaryocytic cell line MEG-01 this inhibition is absent.
      Using human megakaryocytic cell lines representing different stages in
      megakaryocyte (Mk) maturation as well as stem cells and immature and mature
      megakaryocytes, we show that the inhibition by prostacyclin develops at a late
      maturation stage shortly before platelets are formed. This late appearance is not
      caused by insufficient cAMP formation or absent protein kinase A (PKA) activity
      in immature cells. Instead, the appearance of Ca2+ inhibition by prostacyclin is
      accompanied by a sharp increase in the expression of the catalytic subunit of PKA
      (PKA-C) but not by changes in the expression of the PKA-regulatory subunits
      Ialpha/beta, IIalpha, and IIbeta. Overexpression of PKA-C in the megakaryocytic
      cell line CHRF-288-11 potentiates the Ca2+ inhibition by prostacyclin. Thus, up
      regulation of PKA-C appears to be a key step in the development of Ca2+
      inhibition by prostacyclin in platelets.

PMID- 11997387
TI  - Functional characterization of a novel mammalian zinc transporter, ZnT6.
AB  - We describe ZnT6, a new member of the CDF (cation diffusion facilitator) family
      of heavy metal transporters. The human ZNT6 gene was mapped at 2p21-22, while the
      mouse Znt6 was localized to chromosome 17. Overexpression of ZnT6 in both wild
      type yeast and mutants that are deficient in cytoplasmic zinc causes growth
      inhibition, but this inhibition is abolished in mutant cells with high
      cytoplasmic zinc. ZnT6 may function in transporting the cytoplasmic zinc into the
      Golgi apparatus as well as the vesicular compartment, as evidenced by its
      overlapping intracellular localization with TGN38 and transferrin receptor in the
      normal rat kidney cells. We also demonstrate that the intracellular distributions
      of ZnT6 as well as ZnT4 are regulated by zinc in the normal rat kidney cells. The
      results from this report, combined with those from other studies, suggest that
      the intracellular zinc homeostasis is mediated by many ZnT proteins, which act in
      tissue-, cell-, and organelle-specific manners.

PMID- 11997388
TI  - Interplay between calcium, diacylglycerol, and phosphorylation in the spatial and
      temporal regulation of PKCalpha-GFP.
AB  - The function of protein kinase C (PKC) is closely regulated by its subcellular
      localization. We expressed PKCalpha fused to green fluorescent protein (PKCalpha
      GFP) and examined its translocation in living and permeabilized cells of the
      human parotid cell line, HSY-EB. ATP induced an oscillatory translocation of
      PKCalpha-GFP to and from the plasma membrane that paralleled the appearance of
      repetitive Ca2+ spikes. Staurosporine attenuated the relocation of PKCalpha-GFP
      to the cytosol and caused a stepwise accumulation of PKCalpha-GFP at the plasma
      membrane during ATP stimulation. Diacylglycerol enhanced the amplitude and
      duration of the ATP-induced oscillatory translocation of PKCalpha-GFP. Ionomycin
      induced a transient translocation of PKCalpha-GFP to the plasma membrane despite
      the continuous elevation of cytosolic Ca2+. The ionomycin-induced transient
      translocation of PKCalpha-GFP was prolonged by staurosporine, diacylglycerol, and
      phorbol myristate acetate. Experiments using permeabilized cells showed that
      staurosporine or the elimination of ATP and Mg2+ decreases the rate of
      dissociation of PKCalpha-GFP from the membrane. Diacylglycerol slowed the
      dissociation of PKCalpha-GFP from the membrane regardless of the Ca2+
      concentration. The effect of diacylglycerol was attenuated by ATP plus Mg2+ at
      low concentrations of Ca2+ (<500 nm) but not at high concentrations of Ca2+
      (>1000 nm). These data suggest a complex interplay between Ca2+, diacylglycerol,
      and phosphorylation in the regulation of the membrane binding of PKCalpha.

PMID- 11997389
TI  - Conserved amino acids within CCAAT enhancer-binding proteins (C/EBP(alpha) and
      beta) regulate phosphoenolpyruvate carboxykinase (PEPCK) gene expression.
AB  - Thyroid hormone and cAMP stimulate transcription of the gene for
      phosphoenolpyruvate carboxykinase (PEPCK). CCAAT enhancer-binding proteins
      (C/EBP(alpha) and beta) are involved in multiple aspects of the nutritional,
      developmental and hormonal regulation of PEPCK gene expression. Previously, we
      have identified a thyroid hormone response element in the PEPCK promoter and
      demonstrated that C/EBP proteins bound to the P3(I) site are participants in the
      induction of PEPCK gene expression by thyroid hormone and cAMP. Here, we identify
      several peptide regions within the transactivation domain of C/EBP(alpha) that
      enhance the ability of T(3) to stimulate gene transcription. We also demonstrate
      that several conserved amino acids in the transactivation domain of C/EBP(alpha)
      and C/EBPbeta are required for the stimulation of basal gene expression and
      identify amino acids within C/EBPbeta that participate in the cAMP induction of
      the PEPCK gene. Finally, we show that the CREB-binding protein (CBP) enhanced the
      induction of PEPCK gene transcription by thyroid hormone and that CBP is
      associated with the PEPCK gene in vivo. Our results indicate that both C/EBP
      proteins and CBP participate in the regulation of PEPCK gene transcription by
      thyroid hormone.

PMID- 11997390
TI  - Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel
      mechanism of regulation of vitamin E status.
AB  - Postabsorptive elimination of the various forms of vitamin E appears to play a
      key role in regulation of tissue tocopherol concentrations, but mechanisms of
      tocopherol metabolism have not been elucidated. Here we describe a pathway
      involving cytochrome P450-mediated omega-hydroxylation of the tocopherol phytyl
      side chain followed by stepwise removal of two- or three-carbon moieties,
      ultimately yielding the 3'-carboxychromanol metabolite that is excreted in urine.
      All key intermediates of gamma-tocopherol metabolism via this pathway were
      identified in hepatocyte cultures using gas chromatography-mass spectrometry.
      NADPH-dependent synthesis of the initial gamma- and alpha-tocopherol 13'-hydroxy
      and -carboxy metabolites was demonstrated in rat and human liver microsomes.
      Functional analysis of several recombinant human liver P450 enzymes revealed that
      tocopherol-omega-hydroxylase activity was associated only with CYP4F2, which also
      catalyzes omega-hydroxylation of leukotriene B(4) and arachidonic acid.
      Tocopherol-omega-hydroxylase exhibited similar binding affinities but markedly
      higher catalytic activities for gamma-tocopherol than alpha-tocopherol,
      suggesting a role for this pathway in the preferential physiological retention of
      alpha-tocopherol and elimination of gamma-tocopherol. Sesamin potently inhibited
      tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver
      microsomes. Since dietary sesamin also results in elevated tocopherol levels in
      vivo, this pathway appears to represent a functionally significant means of
      regulating vitamin E status.

PMID- 11997391
TI  - Reversible DNA compaction by sulfite reductase regulates transcriptional activity
      of chloroplast nucleoids.
AB  - The transcriptional activity of nucleoids changes during plastid development,
      presumably due to the morphological and molecular differences of the nucleoids.
      Pea chloroplast nucleoids have an abundant 70-kDa protein identified as sulfite
      reductase (SiR) that can compact DNA. Using an in vitro transcription assay, we
      show here that heparin increased the transcriptional activity of chloroplast
      nucleoids with concomitant release of SiR. Using a fluorometric method we
      developed for analyzing DNA compaction, we found that the fluorescence intensity
      of chloroplast DNA stained with 4',6-diamidino-2-phenylindole was decreased by
      the addition of SiR and increased by the subsequent addition of heparin. Addition
      of exogenous SiR increased the compaction of isolated nucleoids, and the addition
      of heparin relaxed it. SiR effectively repressed the in vitro transcription
      activity of nucleoids and counteracted the activation by heparin. These results
      suggest that SiR regulates the transcriptional activity of chloroplast nucleoids
      through changes in DNA compaction.

PMID- 11997392
TI  - A constitutively nuclear form of NFATx shows efficient transactivation activity
      and induces differentiation of CD4(+)CD8(+) T cells.
AB  - The Ca(2+) signal facilitates nuclear translocation of NFAT through the
      dephosphorylation of clustered serine residues in the calcium regulatory domain
      by the Ca(2+)/calmodulin-dependent phosphatase calcineurin. The conformation of
      dephosphorylated NFAT exposes the nuclear localization signal for translocation
      into the nucleus and masks the nuclear export sequence to keep the protein in the
      nucleus. It has been reported that deletion of some serine-rich motifs masking
      the nuclear localization signal results in the translocation of NFAT into the
      nucleus, but that the nuclear export sequence located at the N terminus also
      needs to be deleted for NFATx (NFAT4/NFATc3) to exert efficient transactivation
      function. Here, we report that deletion of the critical serine-rich motifs of
      NFATx leads to a conformation that efficiently exposes the nuclear localization
      signal and that has stronger transcription activity compared with the fully
      activated wild-type protein in the presence of the nuclear export sequence. This
      also suggests that the regulation of the transactivation domain by
      phosphorylation observed in NFAT1 may not contribute significantly to the
      transcription activity of NFATx. The expression of this constitutively nuclear
      form of NFATx in the CD4(+)CD8(+) T cell line facilitates differentiation into
      the CD4 single-positive stage upon stimulation with phorbol ester. Our data
      suggest that NFATx is involved in the regulation of co-receptor expression during
      differentiation into the CD4 single-positive stage.

PMID- 11997393
TI  - Kinetic mechanism of human class IV alcohol dehydrogenase functioning as retinol
      dehydrogenase.
AB  - Molecular genetic studies have indicated that alcohol dehydrogenase may be
      involved in the synthesis of retinoic acid, a hormonal molecule regulating
      diverse cellular functions at the transcriptional level. Class IV alcohol
      dehydrogenase (ADH) has been reported to be the most efficient enzyme catalyzing
      oxidation of retinol in human ADH family. Initial velocity, product inhibition,
      and dead-end inhibition experiments were performed with the recombinant human
      class IV ADH to elucidate kinetic mechanism with all-trans-retinol and all-trans
      retinal as natural substrates. Fluorescence quenching was titrated in formation
      of the binary and abortive ternary enzyme complexes. The minimal mechanism
      deduced from steady-state kinetic and equilibrium binding studies is best
      described as an asymmetric rapid equilibrium random mechanism with two dead-end
      ternary complexes for retinol oxidation and a rapid equilibrium ordered mechanism
      with one dead-end ternary complex for retinal reduction, a unique mechanistic
      form for zinc-containing ADHs in the medium chain dehydrogenase/reductase
      superfamily. Dissociation constants for the binary complexes as well as the
      productive and abortive ternary complexes determined from different experimental
      approaches are in reasonable agreement. Kinetic isotope effect studies suggest
      rate-limiting isomerization of the central ternary complexes in both reaction
      directions. The potential interference of retinol metabolism by ethanol through
      the ADH pathway may play a significant role in the pathogenesis of fetal alcohol
      syndrome and alcohol-related upper digestive tract cancer.

PMID- 11997394
TI  - A functional green fluorescent protein-erythropoietin receptor despite physical
      separation of JAK2 binding site and tyrosine residues.
AB  - Signaling through hematopoietic cytokine receptors such as the erythropoietin
      receptor (EpoR) depends on the activation of a receptor-bound Janus kinase (JAK)
      and tyrosine phosphorylation of the cytoplasmic domain. To visualize the EpoR and
      elucidate structural requirements coordinating signal transduction, we probed the
      EpoR by inserting the green fluorescent protein (GFP) at various positions. We
      show that insertion of GFP in proximity to the transmembrane domain, either in
      the extracellular or the cytoplasmic domain, results in EpoR-GFP receptors
      incompetent to elicit biological responses in a factor-dependent cell line or in
      erythroid progenitor cells. Surprisingly, a receptor harboring GFP insertion in
      the middle of the cytoplasmic domain, and thereby separating the JAK2 binding
      site from the tyrosine residues, is capable of supporting signal transduction in
      response to ligand binding. Comparable with the wild type EpoR, but more
      efficient than a C-terminal EpoR-GFP fusion, this chimeric receptor promotes the
      maturation of erythroid progenitor cells and is localized in punctated endosome
      like structures. We conclude that the extracellular, transmembrane, and membrane
      proximal segment of the cytoplasmic domain form a rigid structural entity whose
      precise orientation is essential for the initiation of signal transduction,
      whereas the cytoplasmic domain possesses flexibility in adopting an activated
      conformation.

PMID- 11997395
TI  - Structural requirements for interaction of sodium channel beta 1 subunits with
      ankyrin.
AB  - Sodium channel beta subunits modulate channel kinetic properties and cell surface
      expression levels and function as cell adhesion molecules. beta 1 and beta 2
      participate in homophilic cell adhesion resulting in ankyrin recruitment to cell
      contact sites. We hypothesized that a tyrosine residue in the cytoplasmic domain
      of beta 1 may be important for ankyrin recruitment and tested our hypothesis
      using beta 1 mutants replacing Tyr(181) with alanine (beta 1Y181A), phenylalanine
      (beta 1Y181F), or glutamate (beta 1Y181E), or a truncated construct deleting all
      residues beyond Tyr(181) (beta 1L182(STOP)). Ankyrin recruitment was observed in
      beta 1L182(STOP), showing that residues Ile(166)-Tyr(181) contain the major
      ankyrin recruiting activity of beta 1. Ankyrin recruitment was abolished in beta
      1Y181E, suggesting that tyrosine phosphorylation of beta 1 may inhibit beta 1
      ankyrin interactions. Ankyrin(G) and beta 1 associate in rat brain membranes and
      in transfected cells expressing beta 1 and ankyrin(G) in the absence of sodium
      channel alpha subunits. beta 1 subunits are recognized by anti-phosphotyrosine
      antibodies following treatment of these cell lines with fibroblast growth factor.
      beta 1 and ankryin(G) association is not detectable in cells following treatment
      with fibroblast growth factor. Ankyrin(G) and beta 1Y181E do not associate even
      in the absence of fibroblast growth factor treatment. beta 1 subunit-mediated
      cell adhesion and ankyrin recruitment may contribute to sodium channel placement
      at nodes of Ranvier. The phosphorylation state of beta 1Y181 may be a critical
      regulatory step in these developmental processes.

PMID- 11997396
TI  - The selective regulation of alpha Vbeta 1 integrin expression is based on the
      hierarchical formation of alpha V-containing heterodimers.
AB  - The integrin beta1 subunit can form a heterodimer with 12 different alpha
      subunits. According to the present model, the expression level of any alphabeta
      complex is regulated by the availability of the specific alpha subunit, whereas
      beta1 subunit is constantly present in a large excess. The expression of several
      heterodimers containing the alphaV subunit seems to be regulated by an identical
      mechanism. The fact that many cells express alphaVbeta1 heterodimer, and that
      this fibronectin/vitronectin receptor may be selectively regulated, compromises
      the present model of the regulation of beta1 and alphaV integrins. We have tried
      to solve this problem by assuming that distinct alphabeta heterodimers are formed
      with different tendency. To test the hypothesis, we analyzed WM-266-4 melanoma
      cells transfected with a cDNA construct coding for an intracellular single-chain
      anti-alphaV integrin antibody. We could see 70-80% reduction in the cell surface
      expression of alphaV subunit. However, the only one of the alphaV integrins
      reduced on the cell surface was alphaVbeta1. This suggests that the cell surface
      expression level of alphaVbeta1 is dependent on the number of alphaV subunits
      available after the formation of other alphaV-containing heterodimers. Thus,
      there seems to be a hierarchy in the complex formation between alphaV and its
      different beta-partners. These observations explain how alphaVbeta1 can be
      specifically regulated without concomitant changes in the expression of other
      alphaV or beta1 integrins.

PMID- 11997397
TI  - The tautomerase active site of macrophage migration inhibitory factor is a
      potential target for discovery of novel anti-inflammatory agents.
AB  - Macrophage migration inhibitory factor (MIF) is an immunoregulatory protein that
      is a potential therapeutic target for a number of inflammatory diseases. Evidence
      exists that an unexpected catalytic active site of MIF may have a biological
      function. To gain further insight into the role of the catalytic active site, a
      series of mutational, structural, and biological activity studies were performed.
      The insertion of an alanine between Pro-1 and Met-2 (PAM) abolishes a non
      physiological catalytic activity, and this mutant is defective in the in vitro
      glucocorticoid counter-regulatory activity of MIF. The crystal structure of MIF
      complexed to (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl
      ester (ISO-1), an inhibitor of MIF d-dopachrome tautomerase activity, reveals
      that ISO-1 binds to the same position of the active site as p
      hydroxyphenylpyruvic acid, a substrate of MIF. ISO-1 inhibits several MIF
      biological activities, further establishing a role for the catalytic active site
      of MIF.

PMID- 11997398
TI  - X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type
      and mutant 4-hydroxybenzoyl-CoA thioesterase.
AB  - The metabolic pathway by which 4-chlorobenzoate is degraded to 4-hydroxybenzoate
      in the soil-dwelling microbe Pseudomonas sp. strain CBS-3 consists of three
      enzymes including 4-hydroxybenzoyl-CoA thioesterase. The structure of the unbound
      form of this thioesterase has been shown to contain the so-called "hot dog" fold
      with a large helix packed against a five-stranded anti-parallel beta-sheet. To
      address the manner in which the enzyme accommodates the substrate within the
      active site, two inhibitors have been synthesized, namely 4-hydroxyphenacyl-CoA
      and 4-hydroxybenzyl-CoA. Here we describe the structural analyses of the enzyme
      complexed with these two inhibitors determined and refined to 1.5 and 1.8 A
      resolution, respectively. These studies indicate that only one protein side
      chain, Ser(91), participates directly in ligand binding. All of the other
      interactions between the protein and the inhibitors are mediated through backbone
      peptidic NH groups, carbonyl oxygens, and/or solvents. The structures of the
      enzyme-inhibitor complexes suggest that both a hydrogen bond and the positive end
      of a helix dipole moment serve to polarize the electrons away from the carbonyl
      carbon of the acyl group, thereby making it more susceptible to nucleophilic
      attack. Additionally, these studies demonstrate that the carboxylate group of
      Asp(17) is approximately 3.2 A from the carbonyl carbon of the acyl group. To
      address the role of Asp(17), the structure of the site-directed mutant protein
      D17N with bound substrate has also been determined. Taken together, these
      investigations suggest that the reaction mechanism may proceed through an acyl
      enzyme intermediate.

PMID- 11997399
TI  - The ubiquitous chromatin protein DEK alters the structure of DNA by introducing
      positive supercoils.
AB  - We have investigated the molecular mechanism by which the proto-oncogene protein
      DEK, an abundant chromatin-associated protein, changes the topology of DNA in
      chromatin in vitro. Band-shift assays and electron microscopy revealed that DEK
      induces both intra- and intermolecular interactions between DNA molecules.
      Binding of the DEK protein introduces constrained positive supercoils both into
      protein-free DNA and into DNA in chromatin. The induced change in topology is
      reversible after removal of the DEK protein. As shown by sedimentation analysis
      and electron microscopy, the DEK-induced positive supercoiling causes distinct
      structural changes of DNA and chromatin. The observed direct effects of DEK on
      chromatin folding help to understand the function that this major chromatin
      protein performs in the nucleus.

PMID- 11997401
TI  - Images in cardiology. Ruptured thoracic aneurysm in a 10 year old boy.

PMID- 11997400
TI  - Contemporary criteria for the selection of patients for percutaneous balloon
      mitral valvuloplasty.

PMID- 11997402
TI  - Prenatal diagnosis of structural heart disease: does it make a difference to
      survival?

PMID- 11997403
TI  - Is surgery still the preferred option for coronary revascularisation in diabetics
      with multivessel coronary disease?

PMID- 11997406
TI  - Images in cardiology. Pyoderma gangrenosum presented as a refractory wound
      infection following permanent pacemaker implantation.

PMID- 11997405
TI  - Short and long term prognostic importance of regional dyskinesia versus akinesia
      in acute myocardial infarction.
AB  - BACKGROUND: The prognostic importance of dyskinesia after acute myocardial
      infarction is unknown, and recommendations have been made that dyskinesia be
      included in calculations of wall motion index (WMI). OBJECTIVE: To determine
      whether it is necessary to distinguish between dyskinesia and akinesia when WMI
      is estimated for prognostic purposes following acute myocardial infarction.
      DESIGN: Multicentre prospective study. PATIENTS: 6676 consecutive patients,
      screened one to six days after acute myocardial infarction in 27 Danish
      hospitals. INTERVENTIONS: WMI was measured in 6232 patients, applying the nine
      segment model, scoring 3 for hyperkinesia, 2 for normokinesia, 1 for hypokinesia,
      0 for akinesia, and -1 for dyskinesia. Calculation of WMI either included
      information on dyskinesia or excluded this information by giving dyskinesia the
      same score as akinesia. MAIN OUTCOME MEASURES: Long term outcome (up to seven
      years) with respect to mortality. RESULTS: Dyskinesia occurred in 673 patients
      (10.8%). In multivariate analysis, WMI was an important prognostic factor, with a
      relative risk of 2.4 (95% confidence interval (CI), 2.2 to 2.7), while dyskinesia
      had no independent long term prognostic importance (relative risk 1.00; 95% CI,
      0.89 to 1.12). For 30 day mortality dyskinesia had a relative risk of 1.23 (95%
      CI, 1.00 to 1.53) (p = 0.045). CONCLUSIONS: Echocardiographic evaluation of left
      ventricular systolic function shortly after an acute myocardial infarct gives
      important prognostic information, but the presence of dyskinesia only has
      prognostic importance for the first 30 days.

PMID- 11997409
TI  - Lipid lowering in patients with diabetes mellitus: what coronary heart disease
      risk threshold should be used?
AB  - OBJECTIVE: To examine the impact for the UK population of providing statin
      treatment for diabetic patients for the primary prevention of coronary heart
      disease at a coronary event risk lower than currently recommended by the National
      Service Framework (NSF) for coronary heart disease. DESIGN: Cross sectional
      survey. SETTING: England 1998. PARTICIPANTS: Nationally representative sample of
      6879 subjects aged 35-74 years living in private households. MAIN OUTCOME
      MEASURES: The proportion of the UK population recommended for statin treatment
      according to the NSF for coronary heart disease, and the proportion of the
      population with diabetes at a coronary disease event risk of > or = 15% over 10
      years. RESULTS: Of the 6879 subjects with total cholesterol measurements, 218
      (3.2%) had diabetes mellitus. In this nationally representative sample, 6.3% of
      the subjects (95% confidence interval (CI), 5.7% to 6.9%) were candidates for
      statin treatment for the secondary prevention of coronary heart disease,
      including 0.7% (95% CI 0.5% to 0.9%) with diabetes. A further 2.4% (95% CI 2.0%
      to 2.8%), including 0.4% (0.2% to 0.6%) with diabetes, were identified as
      candidates for primary prevention of coronary heart disease according to the NSF
      for coronary heart disease. Lowering the primary prevention threshold for statin
      treatment to a coronary event risk of > or = 15% over 10 years in diabetic
      patients identified an additional 0.5% of the population. CONCLUSIONS: Extending
      statin treatment to diabetic patients at a coronary heart disease risk of > or =
      15% over 10 years would have a relatively small numerical impact in the UK
      population. Thus patients with diabetes mellitus should, as a minimum, be
      targeted for statin treatment at this level of risk.

PMID- 11997407
TI  - Prognostic implications of autonomic function assessed by analyses of
      catecholamines and heart rate variability in stable angina pectoris.
AB  - OBJECTIVE: To assess the prognostic impact of autonomic activity, as reflected by
      catecholamines and heart rate variability (HRV), in patients with stable angina
      pectoris. DESIGN: Double blind, randomised treatment with metoprolol or
      verapamil. 24 hour ambulatory ECG, used for frequency domain analyses of HRV, and
      symptom limited exercise tests at baseline and after one month of treatment.
      Catecholamine concentrations were measured in plasma (rest and exercise) and
      urine. SETTING: Single centre at a university hospital. PATIENTS: 641 patients
      (449 men) with stable angina pectoris. MAIN OUTCOME MEASURES: Cardiovascular (CV)
      death, non-fatal myocardial infarction (MI). RESULTS: During follow up (median 40
      months) there were 27 CV deaths and 26 MIs. Patients who died of CV causes had
      lower total power and high (HF), low (LF), and very low (VLF) frequency
      components of HRV. HRV was not altered in patients who suffered non-fatal MI.
      Catecholamines did not differ between patients with and those without events.
      Metoprolol increased HRV. Verapamil decreased noradrenaline (norepinephrine)
      excretion. Multivariate Cox analyses showed that total power, HF, LF, and VLF
      independently predicted CV death (also non-sudden death) but not MI. LF:HF ratios
      and catecholamines were not related to prognosis. Treatment effects on HRV did
      not influence prognosis. CONCLUSIONS: Low HRV predicted CV death but not non
      fatal MI. Neither the LF:HF ratio nor catecholamines carried any prognostic
      information. Metoprolol and verapamil influenced LF, HF, and catecholamines
      differently but treatment effects were not related to prognosis.

PMID- 11997410
TI  - Improvements in total mortality and lipid levels after acute myocardial
      infarction in an English health district (1995-1999).
AB  - OBJECTIVES: To quantify changes in 30 day and one year mortality among patients
      with acute myocardial infarction in southern Derbyshire (population 560 000) in
      each of five consecutive years (1995-1999) before the publication of the National
      Service Framework for coronary heart disease, and to assess the proportion of one
      year survivors in whom serum lipids were measured and were below target values.
      DESIGN: All hospital admissions coded on the patient administration system (PAS)
      as "AMI" (ICD codes I-21, I-22, and I-23) and with a creatine kinase measurement
      in the pathology database were identified over a five year period (n = 4912). All
      deaths in the district are automatically notified to the PAS. Total mortality
      after acute myocardial infarction (30 days and one year) and lipid levels were
      analysed by year of admission, age group (35-74 years v > or = 75 years), and sex
      using unconditional logistic regression analysis. SETTING: An acute hospitals
      trust and pathology laboratory, as sole service providers for a catchment
      population of 560 000. RESULTS: The number of admissions for acute myocardial
      infarction was similar in each of the five years (n = 4912, 62% male, 63% < 75
      years old). Overall, among patients aged 35-74 years there were 396 deaths (13%)
      at 30 days and 585 (19%) at one year; mortality was higher in women (1.28-fold at
      30 days, p = 0.02) and in subjects aged 75 years or more (3.26-fold at 30 days, p
      < 0.0001). There was a progressive reduction in 30 day mortality of 9%/year over
      the five year period (95% confidence interval, 4% to 13%, p = 0.012). The
      proportion of one year survivors (35-74 years) in whom serum lipids were measured
      at least once increased from 74% in 1995 to 88% in 1999; of these, 27% of men and
      23% of women had a total serum cholesterol of < 5 mmol/l in 1995, increasing to
      65% and 74%, respectively, in 1998 and 1999 (p < 0.0001). CONCLUSIONS: In the
      five year period 1995-1999, there was a significant year on year decline in 30
      day and one year mortality after admission for acute myocardial infarction, and
      progressively more patients achieved cholesterol levels below 5 mmol/l. Men were
      more likely than women to have their lipids measured after myocardial infarction.
      Mortality at one year was 1.32-fold higher among women than among men.

PMID- 11997411
TI  - Images in cardiology. Spontaneous recovery from prolonged cardiac arrest.

PMID- 11997412
TI  - Images in cardiology. Single coronary artery and tetralogy of Fallot.

PMID- 11997414
TI  - Images in cardiology. Magnetic resonance angiography showing bilateral subclavian
      artery aneurysm and stenosis in Marfan's syndrome.

PMID- 11997413
TI  - Effect of atrial antitachycardia pacing treatments in patients with an atrial
      defibrillator: randomised study comparing subthreshold and nominal pacing
      outputs.
AB  - OBJECTIVE: To assess the true efficacy of antitachycardia pacing on spontaneous
      persistent atrial fibrillation in patients with an implanted atrial
      defibrillator, by comparing the effects of nominal pacing treatment with
      subthreshold pacing treatment. DESIGN: The effects of antitachycardia pacing and
      burst 50 Hz atrial pacing on spontaneous atrial arrhythmias were evaluated six
      months after implantation of a Medtronic Jewel AF((R)) atrial defibrillator.
      SETTING: Cardiology department in a district general hospital. PATIENTS: 15
      patients with persistent atrial fibrillation. INTERVENTIONS: Patients were
      randomised to either "nominal" output pacing treatment or surface ECG and
      endocardial electrogram proven subthreshold "sham" pacing treatment for three
      months, and then crossed over to the alternative treatment for a further three
      months. RESULTS: During the nominal output phase, 31 episodes of atrial
      fibrillation were treated with 53 bursts of 50 Hz pacing, 98 sequences of ramp
      atrial pacing, and 61 sequences of burst atrial pacing. Atrial fibrillation was
      not pace terminated during any episode. Thirty one episodes of atrial tachycardia
      were treated with 19 bursts of 50 Hz atrial pacing, 103 sequences of ramp atrial
      pacing, and 38 sequences of burst atrial pacing. Termination of atrial
      tachycardia was observed in 17 episodes. During the "sham" pacing period, no
      episodes were terminated by any pacing treatment. CONCLUSION: Atrial
      antitachycardia pacing treatments are ineffective at terminating persistent
      atrial fibrillation but may be useful in terminating episodes of atrial
      tachycardia or flutter, thus reducing the burden of arrhythmia.

PMID- 11997415
TI  - Implantable cardioverter-defibrillators in arrhythmias: a rapid and systematic
      review of effectiveness.
AB  - OBJECTIVE: To review the effectiveness of implantable cardioverter-defibrillators
      (ICDs) in the management of risk factors for sudden cardiac death. DESIGN:
      Systematic review of randomised controlled trials identified from searching eight
      electronic databases, bibliographies of relevant studies, and consulting experts.
      MAIN OUTCOME MEASURES: Absolute and relative reduction in mortality. RESULTS:
      Seven trials met the inclusion criteria. These showed changes in absolute risk of
      total mortality ranging from +1.7% to -22.8% (relative risk reductions -7% to
      +54%). Estimated benefits from ICD treatment compared with conventional drug
      treatment at three years were 0.23 to 0.80 additional years of life. CONCLUSIONS:
      Evidence suggests that ICDs reduce total mortality in particular subgroups of
      patients at high risk of ventricular arrhythmias. The optimal strategy for
      identifying the patients who could benefit most is not clearly established.
      Ongoing trials into the treatment of cardiac failure with ICDs may provide
      further evidence about subgroups in whom ICDs are most cost effective.

PMID- 11997416
TI  - Images in cardiology. Glycoprotein IIb/IIIa induced coronary thrombolysis.

PMID- 11997418
TI  - Images in cardiology. Pneumomediastinum: a cause of chest pain.

PMID- 11997417
TI  - Atrial fibrillation recurrence after internal cardioversion: prognostic
      importance of electrophysiological parameters.
AB  - OBJECTIVE: To evaluate the clinical and electrophysiological determinants of
      arrhythmia recurrence in patients undergoing internal atrial cardioversion for
      chronic atrial fibrillation (AF). SETTING: Tertiary cardiac referral centre.
      METHODS: 101 consecutive patients with failed external cardioversion or AF > or =
      1 year underwent internal atrial cardioversion; once stable sinus rhythm (SR) was
      obtained, electrophysiological study was performed in 73 patients (72%) who gave
      informed consent. Patients were then followed on antiarrhythmic treatment.
      RESULTS: 101 consecutive patients underwent internal atrial cardioversion in the
      period 1996-1999 with 100% conversion to SR; prophylactic antiarrhythmic
      treatment was flecainide (52%), amiodarone (37%), and sotalol (11%). Average
      follow up at first AF recurrence was 18.4 (14.4) months (range 0.1-49.8 months);
      persistence of SR was observed in 72/101 (72%) patients. By logistic regression,
      AF duration (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01 to 1.13) and
      a lower sinus rate at discharge on antiarrhythmic drugs (OR 0.92, 95% CI 0.85 to
      0.99) were independent predictors of AF recurrence, whereas age, New York Heart
      Association functional class, left atrial dimensions, and left ventricular
      ejection fraction were not predictive of arrhythmia recurrence. When
      electrophysiological parameters were added to the statistical model in 73
      patients, a shorter atrial effective refractoriness (OR 1.04, 95% CI 1 to 1.08)
      and an abnormal relation of atrial effective refractoriness to cycle length (OR
      31, 95% CI 3.7 to 266) were also independent predictors of AF recurrence at
      follow up, beyond AF duration and heart rate at discharge. CONCLUSIONS: Patients
      with failed external cardioversion or long lasting AF may benefit from internal
      atrial cardioversion and antiarrhythmic treatment to keep SR at long term;
      electrophysiological study may identify patients at the highest risk of
      arrhythmia recurrence. Although preservation of SR seems unlikely for AF duration
      > 3 years, a consistent minority of this subgroup (38%) may benefit from this
      approach.

PMID- 11997419
TI  - Intrathoracic organ transplantation in the United Kingdom 1995-99: results from
      the UK cardiothoracic transplant audit.
AB  - OBJECTIVE: To describe the current practice and outcomes of intrathoracic
      transplantation in the United Kingdom. DESIGN: Prospective observational cohort
      study. SETTING: Multicentre study involving all nine UK intrathoracic transplant
      units. PATIENTS: 2588 patients added to the national waiting list between April
      1995 and March 1999 and 1737 patients who underwent heart, lung, or heart-lung
      transplantation in the same period. MAIN OUTCOME MEASURES: Waiting list mortality
      and post-transplant graft survival. RESULTS: There was a slight fall in
      transplant activity over the four years. Within six months of listing, 52.5% of
      patients on the heart transplant list had been transplanted and 11.0% had died,
      compared with 31.3% and 15.2% for lung, and 23.4% and 20.4% for heart-lung. The
      median time to transplant in days (95% confidence interval) was 133 (115 to 149)
      for heart, 386 (328 to 496) for lung, and 471 (377 to 577) for heart-lung. After
      three years, the waiting list mortality was 16.9% (6.1% to 46.8%) for heart,
      33.1% (9.0% to 100%) for lung, and 36.5% (10.5% to 100%) for heart-lung. The
      three year graft survival after transplantation was 74.2% (71.2% to 77.0%) for
      heart, 53.8% (48.2% to 59.2%) for lung, and 57.2% (49.0% to 64.6%) for heart
      lung. CONCLUSIONS: This validated database defines the current state of thoracic
      transplantation in the United Kingdom and is a useful source of data for workers
      involved in the field. Thoracic transplantation is still limited by donor
      scarcity and high mortality. Overoptimistic reports may reflect publication bias
      and are not supported by data from this national cohort.

PMID- 11997420
TI  - Images in cardiology. Large fistula between right coronary artery and right
      atrium in a 50 year old asymptomatic woman.

PMID- 11997421
TI  - Early experience with a helical coronary thrombectomy device in patients with
      acute coronary thrombosis.
AB  - OBJECTIVE: To report our experience with a new thrombectomy device (X-SIZER(TM))
      in patients with angiographically visible thrombus or total coronary occlusion in
      the setting of acute coronary syndromes. DESIGN: A safety and feasibility study
      in the use of the X-SIZER during intervention in patients with acute coronary
      syndromes. PATIENTS: 35 patients, age range 31 to 83 years (mean 60). SETTING:
      University Hospitals of Coventry and Warwickshire NHS Trust (tertiary referral
      centre). INTERVENTIONS: The indication for intervention was primary or salvage
      percutaneous coronary intervention for acute myocardial infarction in 17 of the
      35 patients; unstable angina or non-ST-elevation myocardial infarction in 10; and
      unstable postinfarct angina in eight. Abciximab was given in 11 patients. MAIN
      OUTCOME MEASURES: Device success (successful deployment of the device at the site
      of the lesion with resultant improvement in TIMI flow); clinical success (no
      residual stenosis at the end of the procedure with no in-hospital major adverse
      coronary events). RESULTS: Successful use of the device was achieved in 26 of the
      35 cases. It failed to cross the lesion in five and failed to improve TIMI flow
      despite crossing the lesion in four. Clinical success was achieved in 30 of the
      35 cases. Device related complications occurred in two cases (vessel perforation)
      and there was one intraprocedural death (acute myocardial infarction with
      cardiogenic shock). CONCLUSIONS: Thrombectomy with the X-SIZER catheter system
      appears promising in percutaneous coronary intervention where thrombus extraction
      is considered necessary before stent implantation.

PMID- 11997422
TI  - Transcatheter closure of atrial septal defect preserves right ventricular
      function.
AB  - OBJECTIVES: To determine the effects of atrial septal defects (ASD) and their
      closure on systolic and diastolic right and left ventricular function; and by
      comparing surgical closure with transcatheter device closure, to establish
      differences attributable to cardiopulmonary bypass. DESIGN: Cross sectionally
      guided M mode echocardiographic ventricular long axis function was measured
      prospectively before and within one week after ASD closure by device in 17
      patients and by surgery in 12 patients, and compared with 18 normal subjects.
      RESULTS: All indices of right ventricular function were impaired after surgery:
      mean total excursion, -1.89 cm (95% confidence interval (CI), -2.18 to -1.59);
      peak shortening rate, -9.09 cm/s (-10.82 to -7.35); peak lengthening rate, -9.26
      cm/s (-11.09 to -7.43). Total excursion and peak lengthening rate were preserved
      after device closure, at -0.12 cm (-0.28 to 0.05) and 0.01 cm/s (-2.29 to 2.31),
      respectively. Left ventricular free wall function was unchanged after closure by
      either method, while all septal measurements were reduced after closure by either
      method (changes ranging from -3.51 to -0.32; 95% CI ranging from -4.90 to -0.13).
      CONCLUSIONS: Left ventricular free wall function is unaffected by ASD closure,
      whereas septal function is impaired, irrespective of the method of closure. Right
      ventricular function, both systolic and diastolic, is impaired by cardiopulmonary
      bypass but preserved after device closure. These findings support the
      transcatheter approach to ASD closure in anatomically suitable defects.

PMID- 11997423
TI  - Surgical and transcatheter (Amplatzer) closure of atrial septal defects: a
      prospective comparison of results and cost.
AB  - OBJECTIVE: To compare effectiveness, complications, and cost of Amplatzer with
      surgical atrial septal defect (ASD) closure. DESIGN: Prospective study. SETTING:
      Tertiary cardiac referral centre. PATIENTS: 43 consecutive patients (excluding
      non-UK residents) aged between 2.1 and 56.8 years (median 7) undergoing ASD
      closure. MAIN OUTCOME MEASURES: Procedural success, complications, regression of
      right ventricular dilatation (up to one year postprocedure), cost, inpatient
      stay, and home convalescent time. RESULTS: Amplatzer ASD closure was successful
      in 24 of 27 (89%) patients. Surgical closure was successful in all 19 cases.
      Cardiac complications affecting management occurred in three (11%) of the
      Amplatzer group (two procedural failures, one device embolisation) and 4 of 19
      (21%) surgical patients (one pericardial pain, one global pericardial effusion
      requiring drainage, and one patient with anaemia requiring haematinics in
      addition to an incidental pericardial effusion and one further incidental
      pericardial effusion) (p = NS). There were complications that did not affect
      management in a further 5 of 19 surgical patients. There was no significant
      difference in regression of right ventricular dilatation by six months
      postprocedure (median right ventricular end diastolic diameter decrease:
      Amplatzer group 17.5%, surgical group 15.1%; median cardiothoracic ratio
      decrease: Amplatzer 7.9%, surgical 7.5%). Both hospital stay and home
      convalescent times were significantly shorter after Amplatzer closure (median
      hospital stay: Amplatzer one day, surgery six days; median convalescent time:
      Amplatzer two weeks, surgery 5.5 weeks). Median cost was similar for both groups
      (Amplatzer pound5375, surgical pound5412). CONCLUSIONS: Amplatzer ASD closure has
      a lower chance of success with a single procedure than surgery. Overall, there
      were more complications in the surgical group but the majority of these were
      minor and did not require any change in management. Resolution of right
      ventricular dilatation over the study period was similar for both techniques.
      Time spent in hospital and away from work or school was shorter for the Amplatzer
      group. The cost of both techniques was similar.

PMID- 11997424
TI  - Images in cardiology. Haemodynamically insignificant fast ventricular
      tachycardia.

PMID- 11997425
TI  - Pulmonary artery root dilatation in Marfan syndrome: quantitative assessment of
      an unknown criterion.

PMID- 11997427
TI  - Heart disease, guidelines, regulations, and the law.

PMID- 11997428
TI  - Apoptosis in the cardiovascular system.

PMID- 11997429
TI  - Images in cardiology. Development of the human heart: days 15-21.

PMID- 11997430
TI  - Quality of life and psychological functioning of icd patients.

PMID- 11997432
TI  - Images in cardiology. Imaging of a rupture line of an aortic aneurysm by spiral
      CT scan.

PMID- 11997434
TI  - Paracardial lipodystrophy versus pericardial effusion in HIV positive patients.
AB  - OBJECTIVE: To present an epicardial manifestation of the lipodystrophy syndrome,
      a side effect of antiretroviral treatment in HIV positive patients, which
      illustrates the important danger of false diagnosis. PATIENT: A 52 year old man
      with HIV (stage C3), diagnosed 10 years previously, was being treated with a
      combination of nelfinavir, nevirapine, and stavudine. Echocardiographic
      examination showed a low echogenic pericardial space that had increased from 4 mm
      to 18 mm over a 10 month period. The diagnosis of paracardial adipose tissue was
      verified by magnetic resonance tomography. Doppler echocardiographic parameters
      were not significantly altered (ratio of early to late ventricular filling 0.88 v
      0.73, Tei index 0.30 v 0.36). CONCLUSION: Even a pericardial manifestation of
      lipodystrophy causes negligible functional impairment, misinterpretation of the
      lipodystrophy as a pericardial effusion and a subsequent puncture can have
      serious complications. Hence, it is strongly suggested that further differential
      diagnosis be used for HIV positive patients with an echocardiographic suspicion
      of pericardial effusion. Differential diagnosis by magnetic resonance tomography
      is possible.

PMID- 11997435
TI  - Churg-Strauss syndrome with critical endomyocardial fibrosis: 10 year survival
      after combined surgical and medical management.
AB  - A case is presented of the Churg-Strauss syndrome with hypereosinophilia and
      severe cardiac involvement, namely biventricular endomyocardial fibrosis and
      gross encroachment of the right ventricular cavity. The clinical picture was
      similar to Loeffler's syndrome and the idiopathic hypereosinophilic syndrome.
      Combined aggressive surgical and medical management led to full recovery and
      survival at 10 years. The good long term outcome is attributed to strict control
      of peripheral eosinophil count by oral corticosteroids. This case illustrates the
      damaging effects of hypereosinophilia on the heart.

PMID- 11997436
TI  - FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the
      ubiquitin ligase Cbl.
AB  - Attenuation of growth factor signaling is essential for the regulation of
      developmental processes and tissue homeostasis in most organisms. The product of
      Cbl protooncogene is one such regulator, which functions as an ubiquitin ligase
      that ubiquitinates and promotes the degradation of a variety of cell signaling
      proteins. Here, we demonstrate that Grb2 bound to tyrosine-phosphorylated FRS2
      alpha forms a ternary complex with Cbl by means of its Src homology 3 domains
      resulting in the ubiquitination of fibroblast growth factor (FGF) receptor and
      FRS2 alpha in response to FGF stimulation. These observations highlight the
      importance of FRS2 alpha in the assembly of both positive (i.e., Sos,
      phosphatidylinositol 3-kinase) and negative (i.e., Cbl) signaling proteins to
      mediate a balanced FGF signal transduction. However, the partial inhibition of
      FGF receptor down-regulation in FRS2 alpha-/- cells indicates that the
      attenuation of signaling by FGF receptor is regulated by redundant or multiple
      mechanisms.

PMID- 11997437
TI  - The lethal and edema factors of anthrax toxin bind only to oligomeric forms of
      the protective antigen.
AB  - The three proteins that comprise anthrax toxin, edema factor (EF), lethal factor
      (LF), and protective antigen (PA), assemble at the mammalian cell surface into
      toxic complexes. After binding to its receptor, PA is proteolytically activated,
      yielding a carboxyl-terminal 63-kDa fragment (PA(63)) that coordinates assembly
      of the complexes, promotes their endocytosis, and translocates EF and LF to the
      cytosol. PA(63) spontaneously oligomerizes to form symmetric ring-shaped
      heptamers that are capable of binding three molecules of EF and/or LF as
      competing ligands. To determine whether binding of these ligands depends on
      oligomerization of PA(63), we prepared two oligomerization-deficient forms of
      this protein, each mutated on a different PA(63)-PA(63) contact face. In solution
      or when bound to receptors on Chinese hamster ovary K1 cells, neither mutant
      alone bound ligand, but a mixture of them did. After the two mutants were
      proteolytically activated and mixed with ligand in solution, a ternary complex
      was isolated containing one molecule of each protein. Thus EF and LF bind stably
      only to PA(63) dimers or higher order oligomers. These findings are relevant to
      the kinetics and pathways of assembly of anthrax toxin complexes.

PMID- 11997438
TI  - Microrheometry of semiflexible actin networks through enforced single-filament
      reptation: frictional coupling and heterogeneities in entangled networks.
AB  - Magnetic tweezers are applied to study the enforced motion of single actin
      filaments in entangled actin networks to gain insight into friction-mediated
      entanglement in semiflexible macromolecular networks. Magnetic beads are coupled
      to one chain end of test filaments, which are pulled by 5 to 20 pN force pulses
      through entangled solutions of nonlabeled actin, the test filaments thus acting
      as linear force probes of the network. The transient filament motion is analyzed
      by microfluorescence, and the deflection-versus-time curves of the beads are
      evaluated in terms of a mechanical equivalent circuit to determine viscoelastic
      parameters, which are then interpreted in terms of viscoelastic moduli of the
      network. We demonstrate that the frictional coefficient characterizing the
      hydrodynamic coupling of the filaments to the surrounding network is much higher
      than predicted by the tube model, suggesting that friction-mediated interfilament
      coupling plays an important role in the entanglement of non-cross-linked actin
      networks. Furthermore, the local tube width along the filament contour (measured
      in terms of the root-mean-square displacement characterizing the lateral Brownian
      motion of the test filament) reveals strong fluctuations that can lead to
      transient local pinching of filaments.

PMID- 11997439
TI  - Mapping the lethal factor and edema factor binding sites on oligomeric anthrax
      protective antigen.
AB  - Assembly of anthrax toxin complexes at the mammalian cell surface involves
      competitive binding of the edema factor (EF) and lethal factor (LF) to heptameric
      oligomers and lower order intermediates of PA(63), the activated carboxyl
      terminal 63-kDa fragment of protective antigen (PA). We used sequence differences
      between PA(63) and homologous PA-like proteins to delineate a region within
      domain 1' of PA that may represent the binding site for these ligands.
      Substitution of alanine for any of seven residues in or near this region (R178,
      K197, R200, P205, I207, I210, and K214) strongly inhibited ligand binding.
      Selected mutations from this set were introduced into two oligomerization
      deficient PA mutants, and the mutants were used in various combinations to map
      the single ligand site within dimeric PA(63). The site was found to span the
      interface between two adjacent subunits, explaining the dependence of ligand
      binding on PA oligomerization. The locations of residues comprising the site
      suggest that a single ligand molecule sterically occludes two adjacent sites,
      consistent with the finding that the PA(63) heptamer binds a maximum of three
      ligand molecules. These results elucidate the process by which the components of
      anthrax toxin, and perhaps other binary bacterial toxins, assemble into toxic
      complexes.

PMID- 11997440
TI  - A peptide-based fluorescence resonance energy transfer assay for Bacillus
      anthracis lethal factor protease.
AB  - A fluorescence resonance energy transfer assay has been developed for monitoring
      Bacillus anthracis lethal factor (LF) protease activity. A fluorogenic 16-mer
      peptide based on the known LF protease substrate MEK1 was synthesized and found
      to be cleaved by the enzyme at the anticipated site. Extension of this work to a
      fluorogenic 19-mer peptide, derived, in part, from a consensus sequence of known
      LF protease targets, produced a much better substrate, cleaving approximately 100
      times more efficiently. This peptide sequence was modified further on resin to
      incorporate donor/quencher pairs to generate substrates for use in fluorescence
      resonance energy transfer-based appearance assays. All peptides cleaved at
      similar rates with signal/background ranging from 9-16 at 100% turnover. One of
      these substrates, denoted (Cou)Consensus(K(QSY-35)GG)-NH(2), was selected for
      additional assay optimization. A plate-based assay requiring only low nanomolar
      levels of enzyme was developed for screening and inhibitor characterization.

PMID- 11997441
TI  - Single-molecule height measurements on microsomal cytochrome P450 in nanometer
      scale phospholipid bilayer disks.
AB  - The architecture of membrane proteins in their native environment of the
      phospholipid bilayer is critical for understanding physiological function, but
      has been difficult to realize experimentally. In this communication we describe
      the incorporation of a membrane-anchored protein into a supported phospholipid
      bilayer. Cytochrome P450 2B4 solubilized and purified from the hepatic
      endoplasmic reticulum was incorporated into phospholipid bilayer nanostructures
      and oriented on a surface for visualization by atomic force microscopy.
      Individual P450 molecules were observed protruding from the bilayer surface.
      Problems associated with deformation of the protein by the atomic force
      microscopy probe were avoided by analyzing force-dependent height measurements to
      quantitate the height of the protein above the bilayer surface. Measurements of
      the atomic force microscopy cantilever deflection as a function of probe-sample
      separation reveal that the top of the P450 opposite the N-terminal membrane
      anchor region sits 3.5 nanometers above the phospholipid-water boundary. Models
      of the orientation of the enzyme are presented and discussed in relation to
      membrane interactions and interaction with cytochrome P450 reductase.

PMID- 11997442
TI  - Agent-based modeling for understanding social intelligence.
AB  - The advantages of agent-based modeling for a general theory of intelligence at
      the individual and social level are emphasized over other existing approaches
      mainly relying on rationality theories. As was pointed out during the National
      Academy of Sciences Sackler Colloquium session "Implications of Agent-Based
      Modeling for Understanding Human Rationality and Learning," held in October 2001,
      properties of social intelligent agents include adaptability and learning
      capacity, as well as the capacity to produce and employ artifacts and manipulate
      symbols.

PMID- 11997443
TI  - Short-memory traders and their impact on group learning in financial markets.
AB  - This article highlights several issues from simulating agent-based financial
      markets. These all center around the issue of learning in a multiagent setting,
      and specifically the question of whether the trading behavior of short-memory
      agents could interfere with the learning process of the market as whole. It is
      shown in a simple example that short-memory traders persist in generating excess
      volatility and other features common to actual markets. Problems related to short
      memory trader behavior can be eliminated by using several different methods.
      These are discussed along with their relevance to agent-based models in general.

PMID- 11997444
TI  - A multitrajectory, competition model of emergent complexity in human social
      organization.
AB  - The repeated pattern of emergent human organization at a societal level going
      from small-scale, egalitarian decentralized societies to complex, stratified, and
      centralized societies is well-documented in the archaeological record of past
      societies. In this paper, I outline a multitrajectory model that relates to the
      broad features of this sequence of societal change. Competition is shown to play
      a critical role in the way interaction--among decision making, demographic
      parameters, and social units that organize resource ownership and procurement-
      either promotes or inhibits change in social organization. Multiagent simulation
      is discussed as a way to link culturally embedded decision making to emergent
      properties in the multitrajectory model.

PMID- 11997445
TI  - Agent-based modeling: a revolution?
AB  - A clear consensus among the papers in this Colloquium is that agent-based
      modeling is a revolutionary development for social science. However, the reasons
      to expect this revolution lie more in the potential seen in this tool than
      through realized results. In order for the anticipated revolution to occur, a
      series of challenges must be met. This paper surveys the challenges suggested by
      the papers of this session.

PMID- 11997446
TI  - Siderophore-mediated signaling regulates virulence factor production in
      Pseudomonasaeruginosa.
AB  - Numerous bacteria secrete low molecular weight compounds termed siderophores that
      have a high affinity for iron ions. Siderophores have a well-documented role as
      iron-scavenging chemicals, chelating iron ions in the environment whereupon the
      ferrisiderophores reenter the bacterial cells by means of specific cell-surface
      receptors. The iron is then released for incorporation into bacterial proteins.
      Here we show that in addition to its role as an iron-scavenger, the siderophore
      pyoverdine that is secreted by Pseudomonas aeruginosa regulates the production of
      at least three virulence factors (exotoxin A, an endoprotease, and pyoverdine
      itself), which are major contributors to the ability of this bacterium to cause
      disease. Regulation occurs through a transmembrane signaling system that includes
      an outer membrane receptor for ferripyoverdine, a signal-transducing protein that
      is predicted to extend from the periplasm into the cytoplasm, and a sigma factor.
      Expression of genes that form part of the regulon is triggered by pyoverdine so
      that this siderophore acts as a signaling molecule to control the production of
      secreted products. Recognition that a siderophore acts as a signaling molecule
      has important implications for the understanding of interactions between
      bacterial cells.

PMID- 11997447
TI  - Noninvasive imaging of protein-protein interactions in living animals.
AB  - Protein-protein interactions control transcription, cell division, and cell
      proliferation as well as mediate signal transduction, oncogenic transformation,
      and regulation of cell death. Although a variety of methods have been used to
      investigate protein interactions in vitro and in cultured cells, none can analyze
      these interactions in intact, living animals. To enable noninvasive molecular
      imaging of protein-protein interactions in vivo by positron-emission tomography
      and fluorescence imaging, we engineered a fusion reporter gene comprising a
      mutant herpes simplex virus 1 thymidine kinase and green fluorescent protein for
      readout of a tetracycline-inducible, two-hybrid system in vivo. By using micro
      positron-emission tomography, interactions between p53 tumor suppressor and the
      large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa
      cells stably transfected with the imaging constructs. Imaging protein-binding
      partners in vivo will enable functional proteomics in whole animals and provide a
      tool for screening compounds targeted to specific protein-protein interactions in
      living animals.

PMID- 11997448
TI  - Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal
      binding in the active site of phosphotransferase enzymes.
AB  - The process of integrating the reverse-transcribed HIV-1 DNA into the host
      chromosomal DNA is catalyzed by the virally encoded enzyme integrase (IN).
      Integration requires two metal-dependent reactions, 3' end processing and strand
      transfer. Compounds that contain a diketo acid moiety have been shown to
      selectively inhibit the strand transfer reaction of IN in vitro and in infected
      cells and are effective as inhibitors of HIV-1 replication. To characterize the
      molecular basis of inhibition, we used functional assays and binding assays to
      evaluate a series of structurally related analogs. These studies focused on
      investigating the role of the conserved carboxylate and metal binding. We
      demonstrate that an acidic moiety such as a carboxylate or isosteric heterocycle
      is not required for binding to the enzyme complex but is essential for inhibition
      and confers distinct metal-dependent properties on the inhibitor. Binding
      requires divalent metal and resistance is metal dependent with active site
      mutants displaying resistance only when the enzymes are evaluated in the context
      of Mg(2+). The mechanism of action of these inhibitors is therefore likely a
      consequence of the interaction between the acid moiety and metal ion(s) in the IN
      active site, resulting in a functional sequestration of the critical metal
      cofactor(s). These studies thus have implications for modeling active site
      inhibitors of IN, designing and evaluating analogs with improved efficacy, and
      identifying inhibitors of other metal-dependent phosphotransferases.

PMID- 11997449
TI  - Adaptive agents, intelligence, and emergent human organization: capturing
      complexity through agent-based modeling.

PMID- 11997450
TI  - Modeling civil violence: an agent-based computational approach.
AB  - This article presents an agent-based computational model of civil violence. Two
      variants of the civil violence model are presented. In the first a central
      authority seeks to suppress decentralized rebellion. In the second a central
      authority seeks to suppress communal violence between two warring ethnic groups.

PMID- 11997451
TI  - Tools and techniques for developing policies for complex and uncertain systems.
AB  - Agent-based models (ABM) are examples of complex adaptive systems, which can be
      characterized as those systems for which no model less complex than the system
      itself can accurately predict in detail how the system will behave at future
      times. Consequently, the standard tools of policy analysis, based as they are on
      devising policies that perform well on some best estimate model of the system,
      cannot be reliably used for ABM. This paper argues that policy analysis by using
      ABM requires an alternative approach to decision theory. The general
      characteristics of such an approach are described, and examples are provided of
      its application to policy analysis.

PMID- 11997452
TI  - Refined molecular hinge between allosteric and catalytic domain determines
      allosteric regulation and stability of fungal chorismate mutase.
AB  - The yeast chorismate mutase is regulated by tyrosine as feedback inhibitor and
      tryptophan as crosspathway activator. The monomer consists of a catalytic and a
      regulatory domain covalently linked by the loop L220s (212-226), which functions
      as a molecular hinge. Two monomers form the active dimeric enzyme stabilized by
      hydrophobic interactions in the vicinity of loop L220s. The role of loop L220s
      and its environment for enzyme regulation, dimerization, and stability was
      analyzed. Substitution of yeast loop L220s in place of the homologous loop from
      the corresponding and similarly regulated Aspergillus enzyme (and the reverse
      substitution) changed tyrosine inhibition to activation. Yeast loop L220s
      substituted into the Aspergillus enzyme resulted in a tryptophan-inhibitable
      enzyme. Monomeric yeast chorismate mutases could be generated by substituting two
      hydrophobic residues in and near the hinge region. The resulting Thr-212-->Asp
      Phe-28-->Asp enzyme was as stable as wild type, but lost allosteric regulation
      and showed reduced catalytic activity. These results underline the crucial role
      of this molecular hinge for inhibition, activation, quaternary structure, and
      stability of yeast chorismate mutase.

PMID- 11997453
TI  - Endosomal localization and function of sorting nexin 1.
AB  - There are 17 human members of the sorting nexin (SNX) family of proteins that
      contain Phox (PX) domains. Yeast orthologs function in vesicular trafficking and
      mammalian proteins have been implicated in endocytic trafficking of cell surface
      receptors. The first member of this family, SNX1, was identified via interaction
      with the epidermal growth factor receptor. The present studies indicate that SNX1
      and SNX2 are colocalized to tubulovesicular endosomal membranes and this
      localization depends on PI 3-kinase activity. Point mutations in the PX domain
      that abolish recognition of phosphorylated phosphatidylinositol (PtdIns) in vitro
      abolish vesicle localization in vivo indicating that lipid binding by the PX
      domain is necessary for localization to vesicle membranes. Deletion of a
      predicted coiled-coil region in the COOH terminus of SNX1 also abolished vesicle
      localization, indicating that this helical domain, too, is necessary for SNX1
      localization. Thus, both PX domain recognition of PtdIns and COOH terminal
      helical domains are necessary for localization of SNX1 with neither alone being
      sufficient. Regulated overexpression of the NH(2) terminus of SNX1 containing the
      PX domain decreased the rate of ligand-induced epidermal growth factor receptor
      degradation, an effect consistent with inhibition of endogenous SNX1 function in
      the endosome compartment. SNX1 thus functions in regulating trafficking in the
      endosome compartment via PX domain recognition of phosphorylated PtdIns and via
      interaction with other protein components.

PMID- 11997455
TI  - Rescue of a pathogenic Marek's disease virus with overlapping cosmid DNAs: use of
      a pp38 mutant to validate the technology for the study of gene function.
AB  - Marek's disease virus (MDV) genetics has lagged behind that of other
      herpesviruses because of the lack of tools for the introduction of site-specific
      mutations into the genome of highly cell-associated oncogenic strains.
      Overlapping cosmid clones have been successfully used for the introduction of
      mutations in other highly cell-associated herpesviruses. Here we describe the
      development of overlapping cosmid DNA clones from a very virulent oncogenic
      strain of MDV. Transfection of these cosmid clones into MDV-susceptible cells
      resulted in the generation of a recombinant MDV (rMd5) with biological properties
      similar to the parental strain. To demonstrate the applicability of this
      technology for elucidation of gene function of MDV, we have generated a mutant
      virus lacking an MDV unique phosphoprotein, pp38, which has previously been
      associated with the maintenance of transformation in MDV-induced tumor cell
      lines. Inoculation of Marek's disease-susceptible birds with the pp38 deletion
      mutant virus (rMd5 Delta pp38) revealed that pp38 is involved in early cytolytic
      infection in lymphocytes but not in the induction of tumors. This powerful
      technology will speed the characterization of MDV gene function, leading to a
      better understanding of the molecular mechanisms of MDV pathogenesis. In
      addition, because Marek's disease is a major oncogenic system, the knowledge
      obtained from these studies may shed light on the oncogenic mechanisms of other
      herpesviruses.

PMID- 11997454
TI  - The delta subunit of AP-3 is required for efficient transport of VSV-G from the
      trans-Golgi network to the cell surface.
AB  - Vesicular stomatitis virus glycoprotein (VSV-G) is a transmembrane protein that
      functions as the surface coat of enveloped viral particles. We report the
      surprising result that VSV-G uses the tyrosine-based di-acidic motif (-YTDIE-)
      found in its cytoplasmic tail to recruit adaptor protein complex 3 for export
      from the trans-Golgi network. The same sorting code is used to recruit coat
      complex II to direct efficient transport from the endoplasmic reticulum to the
      Golgi apparatus. These results demonstrate that a single sorting sequence can
      interact with sequential coat machineries to direct transport through the
      secretory pathway. We propose that use of this compact sorting domain reflects a
      need for both efficient endoplasmic reticulum export and concentration of VSV-G
      into specialized post-trans-Golgi network secretory-lysosome type transport
      containers to facilitate formation of viral coats at the cell surface.

PMID- 11997456
TI  - Carbocyclic fatty acids in plants: biochemical and molecular genetic
      characterization of cyclopropane fatty acid synthesis of Sterculiafoetida.
AB  - Fatty acids containing three-member carbocyclic rings are found in bacteria and
      plants. Bacteria synthesize cyclopropane fatty acids (CPA-FAs) only by the
      addition of a methylene group from S-adenosylmethionine to the cis-double bond of
      monoenoic phospholipid-bound fatty acids. In plants CPA-FAs are usually minor
      components with cyclopropene fatty acids (CPE-FAs) more abundant. Sterculia
      foetida seed oil contains 65-78% CPE-FAs, principally sterculic acid. To address
      carbocyclic fatty acid synthesis in plants, a cDNA library was constructed from
      developing seeds during the period of maximum oil deposition. About 0.4% of 5,300
      expressed sequence tags were derived from one gene, which shared similarities to
      the bacterial CPA-FA synthase. However, the predicted protein is twice as large
      as the bacterial homolog and represents a fusion of an FAD-containing oxidase at
      the N terminus and a methyltransferase at the C terminus. Functional analysis of
      the isolated full-length cDNA was conducted in tobacco suspension cells where its
      expression resulted in the accumulation of up to 6.2% dihydrosterculate of total
      fatty acids. In addition, the dihydrosterculate was specifically labeled by
      [methyl-(14)C]methionine and by [(14)C]oleic acid in the transgenic tobacco
      cells. In in vitro assay of S. foetida seed extracts, S-adenosylmethionine served
      as a methylene donor for the synthesis of dihydrosterculate from oleate.
      Dihydrosterculate accumulated largely in phosphatidylcholine in both systems.
      Together, a CPA-FA synthase was identified from S. foetida, and the pathway in
      higher plants that produce carbocyclic fatty acids was defined as by transfer of
      C(1) units, most likely from S-adenosylmethionine to oleate.

PMID- 11997457
TI  - The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer.
AB  - The nuclear translocation of peptide hormones, such as the somatolactogenic
      hormone prolactin, after receptor internalization has been widely reported.
      Prolactin has been demonstrated to interact with cyclophilin B, a member of the
      immunophilin family of proteins. Cyclophilin B interaction with prolactin
      potentiated prolactin-induced proliferation, cell growth, and the nuclear
      retrotransport of prolactin. These effects could be abrogated by the removal of
      the peptidyl-prolyl isomerase activity of cyclophilin B. Our findings indicate
      that the intranuclear prolactin/cyclophilin B complex acts as a transcriptional
      inducer by interacting directly with Stat5, resulting in the removal of the Stat
      repressor protein inhibitor of activated Stat 3 (PIAS3), thereby enhancing Stat5
      DNA-binding activity and prolactin-induced, Stat5-mediated gene expression.

PMID- 11997458
TI  - CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS
      from the outer membrane into epithelial cells and activates NF-kappa B
      translocation.
AB  - Immune cells are activated during cellular responses to antigen by two described
      mechanisms: (i) direct uptake of antigen and (ii) extraction and internalization
      of membrane components from antigen-presenting cells. Although endocytosis of
      microbial antigens by pattern recognition molecules (PRM) also activates innate
      immunity, it is not known whether this involves extraction and internalization of
      microbial surface components. Epithelial cells on mucosal surfaces use a variety
      of receptors that are distinct from the classical endocytic PRM to bind and
      internalize intact microorganisms. Nonclassical receptor molecules theoretically
      could act as a type of endocytic PRM if these molecules could recognize, bind,
      extract, and internalize a pathogen-associated molecule and initiate cell
      signaling. We report here that the interaction between the cystic fibrosis
      transmembrane conductance regulator (CFTR) and the outer core oligosaccharide of
      the lipopolysaccharide (LPS) in the outer membrane of Pseudomonas aeruginosa
      satisfies all of these conditions. P. aeruginosa LPS was specifically recognized
      and bound by CFTR, extracted from the organism's surface, and endocytosed by
      epithelial cells, leading to a rapid (5- to 15-min) and dynamic translocation of
      nuclear transcription factor NF-kappa B. Inhibition of epithelial cell
      internalization of P. aeruginosa LPS prevented NF-kappa B activation. Cellular
      activation depended on expression of wild-type CFTR, because both cultured Delta
      F508 CFTR human airway epithelial cells and lung epithelial cells of transgenic
      CF mice failed to endocytose LPS and translocate NF-kappa B. CFTR serves as a
      critical endocytic PRM in the lung epithelium, coordinating the effective innate
      immune response to P. aeruginosa infection.

PMID- 11997459
TI  - Antitumor activity of cytotoxic T lymphocytes engineered to target vascular
      endothelial growth factor receptors.
AB  - The demonstration that angiogenesis is required for the growth of solid tumors
      has fueled an intense interest in the development of new therapeutic strategies
      that target the tumor vasculature. Here we report the development of an immune
      based antiangiogenic strategy that is based on the generation of T lymphocytes
      that possess a killing specificity for cells expressing vascular endothelial
      growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant
      retroviral vectors were generated that encoded a chimeric T cell receptor
      comprised of VEGF sequences linked to intracellular signaling sequences derived
      from the zeta chain of the T cell receptor. After transduction of primary murine
      CD8 lymphocytes by such vectors, the transduced cells were shown to possess an
      efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as
      measured by in vitro cytotoxicity assays. After adoptive transfer into tumor
      bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited
      the growth of a variety of syngeneic murine tumors and human tumor xenografts. An
      increased effect on in vivo tumor growth inhibition was seen when this therapy
      was combined with the systemic administration of TNP-470, a conventional
      angiogenesis inhibitor. The utilization of the immune system to target angiogenic
      markers expressed on tumor vasculature may prove to be a powerful means for
      controlling tumor growth.

PMID- 11997461
TI  - Sex-ratio conflicts, kin selection, and the evolution of altruism.
AB  - Kin-selection theory has thrived in the explanation of a wide variety of
      biological phenomena, chiefly the evolution of biological altruism as that found
      in sterile castes of eusocial insects. Much of the way in which it has been
      tested is based on the existence of conflicts over sex-ratio production within
      eusocial colonies. However, despite neatly showing eusocial colonies as arenas
      where selection at the gene level triggers the appearance of sophisticated
      disputes, these studies have only demonstrated the existence of genes that act by
      biasing sex ratios to promote their own spread. Here we argue that such genes
      depend on the social organization of the colonies where they are expressed, but
      that they are not, in any way, the precursors of these societies-the major
      implication being that unequivocal evidence that eusociality evolved through the
      action of kin-selected altruistic genes is still lacking. Additionally, we
      highlight the neglect of alternative theories on the explanation of both
      biological altruism and sex-ratio conflicts, and defend that the enthusiasm with
      the latter has, in some cases, led to its inappropriate use as a basis for the
      explanation of other biological characteristics of eusocial organisms, when
      accounts based on phylogenetic or physiological constraints are also available.

PMID- 11997460
TI  - Identification of in vivo expressed vaccine candidate antigens from
      Staphylococcus aureus.
AB  - For the design of potent subunit vaccines, it is of paramount importance to
      identify all antigens immunologically recognized by a patient population infected
      with a pathogen. We have developed a rapid and efficient procedure to identify
      such commonly recognized antigens, and here we provide a comprehensive in vivo
      antigenic profile of Staphylococcus aureus, an important human pathogen. S.
      aureus peptides were displayed on the surface of Escherichia coli via fusion to
      one of two outer membrane proteins (LamB and FhuA) and probed with sera selected
      for high Ab titer and opsonic activity. A total of 60 antigenic proteins were
      identified, most of which are located or predicted to be located on the surface
      of the bacterium or secreted. The identification of these antigens and their
      reactivity with individual sera from patients and healthy individuals greatly
      facilitate the selection of promising vaccine candidates for further evaluation.
      This approach, which makes use of whole genome sequence information, has the
      potential to greatly accelerate and facilitate the formulation of novel vaccines
      and is applicable to any pathogen that induces Abs in humans and/or experimental
      animals.

PMID- 11997462
TI  - Neonatal hepatic steatosis by disruption of the adenosine kinase gene.
AB  - Neonatal hepatic steatosis (OMIM 228100) is a fatal condition of unknown etiology
      characterized by a pale and yellow liver and early postnatal mortality. In the
      present study, a deficit in adenosine-dependent metabolism is proposed as a
      causative factor. Physiologically, adenosine is efficiently metabolized to AMP by
      adenosine kinase (ADK), an enzyme highly expressed in liver. ADK not only ensures
      normal adenine nucleotide levels but also is essential for maintaining S
      adenosylmethionine-dependent transmethylation processes, where adenosine, an
      obligatory product, has to be constantly removed. Homozygous Adk(-/-) mutants
      developed normally during embryogenesis. However, within 4 days after birth they
      displayed microvesicular hepatic steatosis and died within 14 days with fatty
      liver. Adenine nucleotides were decreased and S-adenosylhomocysteine, a potent
      inhibitor of transmethylation reactions, was increased in the mutant liver. Thus,
      a deficiency in adenosine metabolism is identified as a powerful contributor to
      the development of neonatal hepatic steatosis, providing a model for the rapid
      development of postnatally lethal fatty liver.

PMID- 11997464
TI  - Elevated mutation rates in the germ line of first- and second-generation
      offspring of irradiated male mice.
AB  - Mutation rates at two expanded simple tandem repeat loci were studied in the germ
      line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and
      BALB/c mice exposed to either high linear energy transfer fission neutrons or low
      linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or
      fission neutrons resulted in increased mutation rates in the germ line of two
      subsequent generations. Comparable transgenerational effects were observed also
      in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of
      spontaneous mutation rates and radiation-induced transgenerational instability
      varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal
      exposure resulted in similar increases in mutation rate in the germ line of both
      generations of CBA/H mice, which together with our previous results suggests that
      radiation-induced expanded simple tandem repeat instability is manifested in
      diploid cells after fertilization. The remarkable finding that radiation-induced
      germ-line instability persists for at least two generations raises important
      issues of risk evaluation in humans.

PMID- 11997466
TI  - Genome-wide screening for trait conferring genes using DNA microarrays.
AB  - We report a DNA microarray-based method for genome-wide monitoring of
      competitively grown transformants to identify genes whose overexpression confers
      a specific cellular phenotype. Whereas transcriptional profiling identifies
      differentially expressed genes that are correlated with particular aspects of the
      cellular phenotype, this functional genomics approach determines genes that
      result in a specific physiology. This parallel gene-trait mapping method consists
      of transforming a strain with a genomic library, enriching the cell population in
      transformants containing the trait conferring gene(s), and finally using DNA
      microarrays to simultaneously isolate and identify the enriched gene inserts.
      Various methods of enrichment can be used; here, genes conferring low-level
      antibiotic resistance were identified by growth in selective media. We
      demonstrated the method by transforming Escherichia coli cells with a genomic E.
      coli library and selecting for transformants exhibiting a growth advantage in the
      presence of the anti-microbial agent Pine-Sol. Genes conferring Pine-Sol
      tolerance (19 genes) or sensitivity (27 genes) were identified by hybridizing, on
      DNA microarrays containing 1,160 E. coli gene probes, extra-chromosomal DNA
      isolated from transformed cells grown in the presence of various levels of Pine
      Sol. Results were further validated by plating and sequencing of individual
      colonies, and also by assessing the Pine-Sol resistance of cells transformed with
      enriched plasmid library or individual resistance genes identified by the
      microarrays. Applications of this method beyond antibiotic resistance include
      identification of genes resulting in resistance to chemotherapeutic agents, genes
      yielding resistance to toxic products (recombinant proteins, chemical feedstocks)
      in industrial fermentations, genes providing enhanced growth in cell culture or
      high cell density fermentations, genes facilitating growth on unconventional
      substrates, and others.

PMID- 11997465
TI  - Telomerase recognizes its template by using an adjacent RNA motif.
AB  - Telomerase adds telomeric repeats to chromosome 3' ends, forestalling the
      cellular senescence, apoptosis, and genomic instability that result from telomere
      loss caused by incomplete DNA replication. The telomerase ribonucleoprotein is
      dedicated to synthesis of tandem, simple-sequence repeats by virtue of its
      specialization for copying only a specific template region within the integral
      RNA. Here, using circularly permuted variants of Tetrahymena thermophila
      telomerase RNA, we identify the features that allow recognition of the template
      region within the RNA. We engineered a template-less telomerase ribonucleoprotein
      that can position and reverse transcribe an exchangeable RNA oligonucleotide
      template accurately. Only a short "template-recognition" element sequence tag is
      required to direct efficient use of adjacent 5' residues as a template for
      telomeric repeat synthesis. Our findings reveal molecular requirements for
      template selection by telomerase and physically resolve templating from other RNA
      functions in catalysis.

PMID- 11997467
TI  - Segregation distortion induced by wild-type RanGAP in Drosophila.
AB  - Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes
      preferential transmission of the SD chromosome from SD/SD(+) males owing to the
      induced dysfunction of SD(+) spermatids. The key distorter locus, Sd, is a
      dominant neomorphic allele encoding a truncated, but enzymatically active, RanGAP
      (RanGTPase-activating protein) whose nuclear mislocalization underlies distortion
      by disrupting the Ran signaling pathway. Here, we show that even wild-type RanGAP
      can cause segregation distortion when it is overexpressed in the male germ line
      or when the gene dosage of a particular modifier locus is increased. Both
      manipulations result in substantial nuclear accumulation of RanGAP. Distortion
      can be suppressed by overexpression of Ran or Ran guanine nucleotide exchange
      factor (RanGEF) in the male germ line, indicating that the primary consequence of
      nuclear mislocalization of RanGAP is reduction of intranuclear RanGTP levels.
      These results prove that segregation distortion does not depend on any unique
      properties of the mutant RanGAP encoded by Sd and provide a unifying explanation
      for the occurrence of distortion in a variety of experimental situations.

PMID- 11997468
TI  - Centripetal and centrifugal reorganizations of frequency map of auditory cortex
      in gerbils.
AB  - As repetitive acoustic stimulation and auditory conditioning do, electric
      stimulation of the primary auditory cortex (AI) evokes reorganization of the
      frequency map of AI, as well as of the subcortical auditory nuclei. The
      reorganization is caused by shifts in best frequencies (BFs) of neurons either
      toward (centripetal) or away from (centrifugal) the BF of stimulated cortical
      neurons. In AI of the Mongolian gerbil, we found that focal electrical
      stimulation evoked a centripetal BF shift in an elliptical area centered at the
      stimulated neurons and a centrifugal BF shift in a zone surrounding it. The 1.9
      mm long major and 1.1-mm long minor axes of the elliptical area were parallel and
      orthogonal to the frequency axis, respectively. The width of the surrounding zone
      was 0.2-0.3 mm. Such "center-surround" reorganization has not yet been found in
      any sensory cortex except AI of the gerbil. The ellipse is similar to the
      arborization pattern of pyramidal neurons, the major source of excitatory
      horizontal connections in AI, whereas the surrounding zone is compatible to the
      arborization range of small basket cells (inhibitory neurons) in AI.

PMID- 11997469
TI  - Mayolenes: labile defensive lipids from the glandular hairs of a caterpillar
      (Pieris rapae).
AB  - Larvae of the European cabbage butterfly, Pieris rapae (Pieridae), are beset with
      glandular hairs, bearing droplets of a clear oily secretion at their tip. The
      fluid consists primarily of a series of chemically labile, unsaturated lipids,
      the mayolenes, which are derived from 11-hydroxylinolenic acid. In bioassays with
      the ant Crematogaster lineolata, the secretion was shown to be potently
      deterrent, indicating that the fluid plays a defensive role in nature.

PMID- 11997470
TI  - Toward development of a screen to identify randomly encoded, foldable sequences.
AB  - The ability to identify sequences in a randomly encoded polypeptide library that
      are capable of acquiring unique and stably folded structures would be valuable in
      the examination of protein-folding issues. The quality control system of the
      yeast secretory pathway prevents the release of incompletely folded polypeptides.
      Earlier work has shown that this feature can be used in a screen to identify
      mutations that increase the stability of a protein. We sought to extend this
      strategy for use with random sequence libraries by combining a quality-control
      system-based screen with generic tag-based immunodetection that can be applied to
      any sequence. To test this method, we screened a library encoding random
      mutations in a bovine pancreatic trypsin inhibitor variant containing a small
      generic tag. Initial on-plate screening resulted in a large number of false
      positives: sequences that were secreted but not foldable. These false positives
      were excluded successfully in additional screening steps that used a liquid
      culture secretion screen and a gel electrophoresis assay. Three positive clones
      were obtained that showed midpoint thermal denaturation temperatures 10-16
      degrees C higher than the original bovine pancreatic trypsin inhibitor variant.
      Thus, this multistep screening method may be useful for finding novel, foldable
      sequences.

PMID- 11997471
TI  - The iscS gene is essential for the biosynthesis of 2-selenouridine in tRNA and
      the selenocysteine-containing formate dehydrogenase H.
AB  - Three NifS-like proteins, IscS, CSD, and CsdB, from Escherichia coli catalyze the
      removal of sulfur and selenium from L-cysteine and L-selenocysteine,
      respectively, to form L-alanine. These enzymes are proposed to function as sulfur
      delivery proteins for iron-sulfur cluster, thiamin, 4-thiouridine, biotin, and
      molybdopterin. Recently, it was reported that selenium mobilized from free
      selenocysteine is incorporated specifically into a selenoprotein and tRNA in
      vivo, supporting the involvement of the NifS-like proteins in selenium
      metabolism. We here report evidence that a strain lacking IscS is incapable of
      synthesizing 5-methylaminomethyl-2-selenouridine and its precursor 5
      methylaminomethyl-2-thiouridine (mnm(5)s(2)U) in tRNA, suggesting that the sulfur
      atom released from L-cysteine by the action of IscS is incorporated into
      mnm(5)s(2)U. In contrast, neither CSD nor CsdB was essential for production of
      mnm(5)s(2)U and 5-methylaminomethyl-2-selenouridine. The lack of IscS also caused
      a significant loss of the selenium-containing polypeptide of formate
      dehydrogenase H. Together, these results suggest a dual function of IscS in
      sulfur and selenium metabolism.

PMID- 11997472
TI  - Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for
      binding to gp120-CD4-CCR5 complexes.
AB  - HIV-1 entry into cells involves formation of a complex between gp120 of the viral
      envelope glycoprotein (Env), a receptor (CD4), and a coreceptor, typically CCR5.
      Here we provide evidence that purified gp120(JR-FL)-CD4-CCR5 complexes exhibit an
      epitope recognized by a Fab (X5) obtained by selection of a phage display library
      from a seropositive donor with a relatively high broadly neutralizing serum
      antibody titer against an immobilized form of the trimolecular complex. X5 bound
      with high (nM) affinity to a variety of Envs, including primary isolates from
      different clades and Envs with deleted variable loops (V1, -2, -3). Its binding
      was significantly increased by CD4 and slightly enhanced by CCR5. X5 inhibited
      infection of peripheral blood mononuclear cells by a selection of representative
      HIV-1 primary isolates from clades A, B, C, D, E, F, and G with an efficiency
      comparable to that of the broadly neutralizing antibody IgG1 b12. Furthermore, X5
      inhibited cell fusion mediated by Envs from R5, X4, and R5X4 viruses. Of the five
      broadly cross-reactive HIV-1-neutralizing human monoclonal antibodies known to
      date, X5 is the only one that exhibits increased binding to gp120 complexed with
      receptors. These findings suggest that X5 could possibly be used as entry
      inhibitor alone or in combination with other antiretroviral drugs for the
      treatment of HIV-1-infected individuals, provide evidence for the existence of
      conserved receptor-inducible gp120 epitopes that can serve as targets for potent
      broadly cross-reactive neutralizing antibodies in HIV-1-infected patients, and
      have important conceptual and practical implications for the development of
      vaccines and inhibitors.

PMID- 11997473
TI  - Reproductive skew in the polygynandrous acorn woodpecker.
AB  - Reproductive skew models, which focus on the degree to which reproduction is
      shared equally (low skew) or monopolized by a single individual (high skew)
      within groups, have been heralded as providing a general unifying framework for
      understanding the factors determining social evolution. Here, we test the ability
      of optimal skew, or "transactional," models, which predict the level of skew
      necessary to promote stable associations of dominants and subordinates, rather
      than independent breeding, to predict reproductive partitioning in the acorn
      woodpecker (Melanerpes formicivorus). This species provides a key test case
      because only a few vertebrates exhibit polygynandry (multiple breeders of both
      sexes within a group). Contrary to the predictions of the models, joint-nesting
      females share reproduction more equitably than expected, apparently because egg
      destruction and the inability of females to defend their eggs from cobreeders
      eliminate any possibility for one female to control reproduction. For males,
      however, reproductive skew is high, with the most successful male siring over
      three times as many young as the next most successful male. Although this result
      is consistent with optimal skew models, other aspects of male behavior are not;
      in particular, the reproductively most successful male frequently switches
      between nests produced by the same set of cobreeders, and we were unable to
      detect any phenotypic correlate of success. These results are consistent with an
      alternative null model in which cobreeder males have equal chance of paternity,
      but paternity of offspring within broods is nonindependent as a consequence of
      female, rather than male, control.

PMID- 11997474
TI  - Dynamin-dependent and dynamin-independent processes contribute to the regulation
      of single vesicle release kinetics and quantal size.
AB  - Accumulating evidence suggests that the kinetics of release from single secretory
      vesicles can be regulated and that quantal size can be modified during fast kiss
      and-run fusion. Multiple pathways for vesicle retrieval have been identified
      involving clathrin and dynamin. It has been unclear whether dynamin could
      participate in a fast kiss-and-run process to reclose a transient fusion pore and
      thereby limit vesicle release. We have disrupted dynamin function in adrenal
      chromaffin cells by expression of the amphiphysin Src-homology domain 3 (SH3) or
      by application of guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), and have
      monitored single vesicle release events, evoked by digitonin and Ca(2+), by using
      carbon-fiber amperometry. Under both conditions, there was an increase in mean
      quantal size accompanying an increase in the half-width of amperometric spikes
      and a slowing of the fall time. These data suggest the existence of a dynamin
      dependent process that can terminate vesicle release under basal conditions.
      Protein kinase C activation changed release kinetics and decreased quantal size
      by shortening the release period. The effects of phorbol ester treatment were not
      prevented by expression of the amphiphysin SH3 domain or by GTP gamma S
      suggesting the existence of alternative dynamin-independent process underlying
      fast kiss-and-run exocytosis.

PMID- 11997475
TI  - Energetics of glycerol conduction through aquaglyceroporin GlpF.
AB  - Aquaglyceroporin GlpF selectively conducts water and linear polyalcohols, such as
      glycerol, across the inner membrane of Escherichia coli. We report steered
      molecular dynamics simulations of glycerol conduction through GlpF, in which
      external forces accelerate the transchannel conduction in a manner that preserves
      the intrinsic conduction mechanism. The simulations reveal channel-glycerol
      hydrogen bonding interactions and the stereoselectivity of the channel. Employing
      Jarzynski's identity between free energy and irreversible work, we reconstruct
      the potential of mean force along the conduction pathway through a time series
      analysis of molecular dynamics trajectories. This potential locates binding sites
      and barriers inside the channel; it also reveals a low energy periplasmic
      vestibule suited for efficient uptake of glycerol from the environment.

PMID- 11997476
TI  - Smooth muscle-selective deletion of guanylyl cyclase-A prevents the acute but not
      chronic effects of ANP on blood pressure.
AB  - Atrial natriuretic peptide (ANP) is an important regulator of arterial blood
      pressure. The mechanisms mediating its hypotensive effects are complex and
      involve the inhibition of the sympathetic and renin-angiotensin-aldosterone (RAA)
      systems, increased diuresis/natriuresis, vasodilation, and enhanced vascular
      permeability. In particular, the contribution of the direct vasodilating effect
      of ANP to the hypotensive actions remains controversial, because variable levels
      of the ANP receptor, guanylyl cyclase A (GC-A), are expressed in different
      vascular beds. The objective of our study was to determine whether a selective
      deletion of GC-A in vascular smooth muscle would affect the hypotensive actions
      of ANP. We first created a mutant allele of mouse GC-A by flanking a required
      exon with loxP sequences. Crossing floxed GC-A with SM22-Cre transgene mice
      expressing Cre recombinase in smooth muscle cells (SMC) resulted in mice in which
      vascular GC-A mRNA expression was reduced by approximately 80%. Accordingly, the
      relaxing effects of ANP on isolated vessels from these mice were abolished;
      despite this fact, chronic arterial blood pressure of awake SMC GC-A KO mice was
      normal. Infusion of ANP caused immediate decreases in blood pressure in floxed GC
      A but not in SMC GC-A knockout mice. Furthermore, acute vascular volume
      expansion, which causes release of cardiac ANP, did not affect resting blood
      pressure of floxed GC-A mice, but rapidly and significantly increased blood
      pressure of SMC GC-A knockout mice. We conclude that vascular GC-A is dispensable
      in the chronic and critical in the acute moderation of arterial blood pressure by
      ANP.

PMID- 11997477
TI  - Reversible cardiac fibrosis and heart failure induced by conditional expression
      of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes.
AB  - Cardiac failure is a common feature in the evolution of cardiac disease. Among
      the determinants of cardiac failure, the renin-angiotensin-aldosterone system has
      a central role, and antagonism of the mineralocorticoid receptor (MR) has been
      proposed as a therapeutic strategy. In this study, we questioned the role of the
      MR, not of aldosterone, on heart function, using an inducible and cardiac
      specific transgenic mouse model. We have generated a conditional knock-down model
      by expressing solely in the heart an antisense mRNA directed against the murine
      MR, a transcription factor with unknown targets in cardiomyocytes. Within 2-3 mo,
      mice developed severe heart failure and cardiac fibrosis in the absence of
      hypertension or chronic hyperaldosteronism. Moreover, cardiac failure and
      fibrosis were fully reversible when MR antisense mRNA expression was subsequently
      suppressed.

PMID- 11997478
TI  - Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential
      enzyme for isoprenoid biosynthesis and target for antimicrobial drug development.
AB  - The crystal structure of the zinc enzyme Escherichia coli 2C-methyl-d-erythritol
      2,4-cyclodiphosphate synthase in complex with cytidine 5'-diphosphate and Mn(2+)
      has been determined to 1.8-A resolution. This enzyme is essential in E. coli and
      participates in the nonmevalonate pathway of isoprenoid biosynthesis, a critical
      pathway present in some bacterial and apicomplexans but distinct from that used
      by mammals. Our analysis reveals a homotrimer, built around a beta prism,
      carrying three active sites, each of which is formed in a cleft between pairs of
      subunits. Residues from two subunits recognize and bind the nucleotide in an
      active site that contains a Zn(2+) with tetrahedral coordination. A Mn(2+), with
      octahedral geometry, is positioned between the alpha and beta phosphates acting
      in concert with the Zn(2+) to align and polarize the substrate for catalysis. A
      high degree of sequence conservation for the enzymes from E. coli, Plasmodium
      falciparum, and Mycobacterium tuberculosis suggests similarities in secondary
      structure, subunit fold, quaternary structure, and active sites. Our model will
      therefore serve as a template to facilitate the structure-based design of
      potential antimicrobial agents targeting two of the most serious human diseases,
      tuberculosis and malaria.

PMID- 11997479
TI  - The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in
      response to intracellular levels of glutamine.
AB  - The essential, rapamycin-sensitive TOR kinases regulate a diverse set of cell
      growth-related readouts in response to nutrients. Thus, the yeast TOR proteins
      function as nutrient sensors, in particular as sensors of nitrogen and possibly
      carbon. However, the nutrient metabolite(s) that acts upstream of TOR is unknown.
      We investigated the role of glutamine, a preferred nitrogen source and a key
      intermediate in yeast nitrogen metabolism, as a possible regulator of TOR. We
      show that the glutamine synthetase inhibitor L-methionine sulfoximine (MSX)
      specifically provokes glutamine depletion in yeast cells. MSX-induced glutamine
      starvation caused nuclear localization and activation of the TOR-inhibited
      transcription factors GLN3, RTG1, and RTG3, all of which mediate glutamine
      synthesis. The MSX-induced nuclear localization of GLN3 required the TOR
      controlled, type 2A-related phosphatase SIT4. Other TOR-controlled transcription
      factors, GAT1/NIL1, MSN2, MSN4, and an unknown factor involved in the expression
      of ribosomal protein genes, were not affected by glutamine starvation. These
      findings suggest that the TOR pathway senses glutamine. Furthermore, as glutamine
      starvation affects only a subset of TOR-controlled transcription factors, TOR
      appears to discriminate between different nutrient conditions to elicit a
      response appropriate to a given condition.

PMID- 11997480
TI  - Specific aneusomies in Chinese hamster cells at different stages of neoplastic
      transformation, initiated by nitrosomethylurea.
AB  - Aneuploidy is ubiquitous in cancer, and its phenotypes are inevitably dominant
      and abnormal. In view of these facts we recently proposed that aneuploidy is
      sufficient for carcinogenesis generating cancer-specific aneusomies via a chain
      reaction of autocatalytic aneuploidizations. According to this hypothesis a
      carcinogen initiates carcinogenesis via a random aneuploidy. Aneuploidy then
      generates transformation stage-specific aneusomies and further random aneusomies
      autocatalytically, because it renders chromosome segregation and repair
      mechanisms error-prone. The hypothesis predicts that several specific aneusomies
      can cause the same cancers, because several chromosomes also cooperate in normal
      differentiation. Here we describe experiments on the Chinese hamster (CH) that
      confirm this hypothesis. (i) Random aneuploidy was detected before transformation
      in up to 90% of CH embryo cells treated with the carcinogen nitrosomethylurea
      (NMU). (ii) Several specific aneusomies were found in 70-100% of the aneuploid
      cells from colonies transformed with NMU in vitro and from tumors generated by
      NMU-transformed cells in syngeneic animals. Among the aneuploid in vitro
      transformed cells, 79% were trisomic for chromosome 3, and 59% were monosomic for
      chromosome 10, compared with 8% expected for random distribution of any aneusomy
      among the 12 CH chromosomes. Moreover, 52% shared both trisomy 3 and monosomy 10
      compared with 0.6% expected for random distribution of any two aneusomies. Among
      the tumor cells, 65% were trisomic for chromosome 3, 51% were trisomic for
      chromosome 5, and 30% shared both trisomies. Aneuploid cells without these
      specific aneusomies may contain minor transformation-specific aneusomies or may
      be untransformed. (iii) Random aneusomies and structurally altered chromosomes
      increased with the generations of transformed cells to the point where their
      origins became unidentifiable in tumors. We conclude that specific aneusomies are
      necessary for carcinogenesis.

PMID- 11997481
TI  - Widening the sphere of influence: using a tool to extend extrapersonal visual
      space in a patient with severe neglect.
AB  - We report evidence that visual representations of space close to the body can be
      extended when a patient uses a tool to explore the environment. HB had severe
      neglect of left and far spatial regions which was determined more by how
      locations were visually perceived than by how they were represented tactilely or
      through proprioception. His ability to detect visual targets in left and far
      space was improved, however, when he held a tool. He also had limited
      tactile/proprioceptive knowledge about the location of his hand. These data
      suggest that by holding a tool, HB's more intact representation of near, visual
      space could be extended to include stimuli presented at a distance from his body.
      This extension of space improved his detection of visual stimuli. We discuss the
      implications of the results for the nature of our internal representation of
      space.

PMID- 11997482
TI  - The role of semantic knowledge in short-term memory.
AB  - In this paper we examine the role of stored semantic knowledge in recall from
      short-term memory. We assessed the performance of a patient (FK), who showed a
      consistent lack of semantic knowledge for some words ('unknown') but not others
      ('known') on a range of serial recall tasks using both spoken and written words.
      Overall, FK was significantly better at recalling lists of known compared with
      unknown words. His recall of unknown words was characterized by numerous
      phonological errors, such as repeating 'bear skunk' as 'bunk scare'. FK showed a
      relatively normal primacy effect in immediate recall, but a striking lack of a
      recency effect. This pattern of performance is useful for constraining
      theoretical accounts of language production and verbal short-term memory and for
      understanding the role that long-term semantic knowledge may play in maintaining
      information in short-term memory.

PMID- 11997483
TI  - Cognition in a patient with very mild right-sided hemiparkinsonism.
AB  - Non-demented patients with Parkinson's disease (PD), especially if they are high
      functioning and early in the course of their disease, usually exhibit mild
      deficits in anterograde recall memory for verbal and non-verbal material,
      visuospatial reasoning, visuomotor construction, temporal ordering and
      sequencing. Impairments in problem solving and verbal fluency tests may also
      occur. PD patients with predominantly right-sided symptoms usually exhibit more
      severe difficulties with verbal than with non-verbal tasks. We report a case of a
      highly educated right-handed man with very mild right-sided hemiparkinsonism who
      never received anti-Parkinsonian or other psychoactive medication. Our patient
      showed anterograde and retrograde amnesia for faces and spatial locations and
      difficulties on complex visuospatial tasks that required manual responses, but
      normal to above average performance on all other cognitive tests. The specific
      pattern of cognitive loss early in PD may depend on which spatial, facial or
      verbal pre-frontal striatal circuits are deprived of their dopaminergic inputs.

PMID- 11997484
TI  - A case study of pure word deafness: modularity in auditory processing?
AB  - AL, a woman with an acquired disturbance of auditory processing beginning in the
      second decade, was originally diagnosed as having pure word deafness. Recent
      analysis with a wide range of stimuli suggests that her comprehension deficit
      also extends to a subset of musical and non-verbal environmental sounds. The
      perceptual demands of the different auditory stimuli appear to account for part
      of the apparent material specificity. Additionally, over the years, the presumed
      temporal lobe cortical pathology has been supplemented by a mild to moderate,
      peripheral low-frequency hearing loss and evidence of dysfunction in lower level
      auditory processing pathways. The current peripheral dysfunction closely
      resembles cases recently labeled as auditory neuropathy. The diagnosis of pure
      word deafness should not be based on a limited set of auditory stimuli;
      additionally, a careful assessment using modern audiological techniques should be
      performed to evaluate peripheral auditory functions.

PMID- 11997485
TI  - The cognitive neuropsychology of everyday actions.

PMID- 11997486
TI  - Order and disorder in everyday action: the roles of contention scheduling and
      supervisory attention.
AB  - This paper describes the contention scheduling/supervisory attentional system
      approach to action selection and uses this account to structure a survey of
      current theories of the control of action. The focus is on how such theories
      account for the types of error produced by some patients with frontal and/or left
      temporoparietal damage when attempting everyday tasks. Four issues, concerning
      both the theories and their accounts of everyday action breakdown, emerge: first,
      whether multiple control systems, each capable of controlling action in different
      situations, exist; second, whether different forms of damage at the neural level
      result in conceptually distinct disorders; third, whether semantic/conceptual
      knowledge of objects and actions can be dissociated from control mechanisms, and
      if so what computational principles govern sequential control; and fourth,
      whether disorders of everyday action should be attributed to a loss of
      semantic/conceptual knowledge, a malfunction of control, or some combination of
      the two.

PMID- 11997487
TI  - The organization of visually mediated actions in a subject without eye movements.
AB  - We investigated the visual strategy of a subject without eye movements (AI),
      comparing her with normal subjects on the 'real-life' task of making a cup of
      tea. Differences in overall performance were surprisingly few. She took no more
      time than the controls to complete the tea-making task and the division of the
      task into object-related actions was essentially similar. However, the way AI
      took in visual information was very different from the normal subjects who used a
      typical 'saccade and fixate' strategy when moving between and scrutinizing
      objects. AI made saccades with the head, which were on average 1.5 times larger
      than the eye-head saccades of the controls and lasted four times as long, meaning
      that AI would have had impaired vision for more of the time than the controls.
      She also made only approximately one-third as many saccades as normals during the
      same task. However, she had another strategy, 'slow drift', in which she allowed
      her eyes to move smoothly across the scene at speeds of up to 30 degrees /s. Such
      movements were never seen in the controls, and we assume that AI used them to
      offset the cost in time of the slow head saccades, even though they had their own
      cost in terms of reduced resolution. We demonstrate that these differences have a
      minimal effect on the timings of events during an object-related action. We
      discuss supervisory checking operations within actions, and consider what
      information is needed for appropriate gaze control during object-related actions.

PMID- 11997488
TI  - Action sequencing deficit following frontal lobe lesion.
AB  - Frontal lobe patients carried out temporal sequencing tasks related to actions
      that differed in terms of their abstractness using both verbal and pictorial
      presentations. A generalized impairment was found: neither a type of action
      effect nor a modality of item presentation effect was present. The patients also
      carried out a corresponding action production task and produced actions quickly
      and without errors. The frontal lobe patients were also spared in generating
      verbal descriptions of actions: they were as accurate as normal controls both in
      terms of the details reported and in maintaining the temporal sequence. It has
      been argued that the difficulty in processing the temporal dimensions of actions
      following frontal lobe lesions is due to some form of disruption of the action
      representation. However, no action representational deficits were present in our
      frontal lobe patients. Thus, they cannot account for our findings. On the
      contrary, we suggest that the action sequencing deficit was a consequence of the
      difficulties patients experienced in rejecting wrong alternatives presented by
      the stimulus situation.

PMID- 11997489
TI  - Dissociations between object knowledge and everyday action.
AB  - We report the case of a patient, MC, with Alzheimer's disease, who showed poor
      ability to name visually presented objects and poor visual access to the concepts
      of objects relative to a group of control patients (also with dementia). She
      performed well when words instead of objects were used in the various tasks. The
      data suggest that she has impaired access to semantic knowledge from vision.
      Surprisingly, she performed well when asked to perform everyday tasks with the
      same objects that had proved problematic in tests of visual naming and semantics.
      MC's pattern of performance is consistent with there being a direct route from
      vision to action and with the proposal that chaining between actions allows the
      development of action schemas which may operate even when there is impaired
      access to semantic knowledge.

PMID- 11997490
TI  - Action-based memory in Alzheimer's disease: a longitudinal look at tea making.
AB  - In this paper we report the results of a longitudinal study which examined memory
      for a single routine activity of daily living in people with dementia of the
      Alzheimer type. We assessed memory in a natural setting, visiting volunteers in
      their homes. We video-taped performance on the selected task and analysed the
      record for the presence or absence of each of its component actions over a period
      of 6 years. In this way, we obtained longitudinal data for a small group of
      people moving from the mild-moderate stages of dementia through to severe
      dysfunction. In the first section of this paper we examine the nature of the
      errors which are made in recall of a routine activity by volunteers with dementia
      of the Alzheimer type and what happens to that routine as the dementia erodes
      memory. In the second section we examine the consequence of moving the routine
      from a familiar setting to a novel setting. We observed large differences in the
      rate of decline of our volunteers, with substantial preservation of performed
      recall of the everyday task, even in the more severe phases of the disease. The
      pattern of decline suggests a benign degradation of the memory trace, with
      omissions comprising the most common category of errors, and this result is
      contrasted with the more dramatic action disorganization syndrome associated with
      frontal injury. The results have implications both for theoretical models of
      action-based memory and intervention programmes aimed at maintaining functional
      independence for people with dementia.

PMID- 11997491
TI  - The influence of personal familiarity and context on object use in semantic
      dementia.
AB  - Several laboratory experiments assessing the ability of patients with semantic
      dementia to use familiar objects have revealed deficits corresponding directly to
      the patients' remaining conceptual knowledge for the same items. The same
      patients, however, were reported to demonstrate normal use of some objects
      relevant to their everyday lives. The study reported here was designed to explore
      this apparent discrepancy by examining the influence of personal familiarity with
      object exemplars, and of the contexts in which they are typically used. Two
      patients with severe semantic impairment were given single objects that they were
      still using at home on a regular basis and asked to demonstrate the use of each.
      Performance on these items was compared with use of perceptually similar and
      perceptually different exemplars of the same objects. All three sets were tested
      in the patients' own homes and also in the laboratory. Both patients were
      significantly more successful at using their own objects than the perceptually
      different exemplars, while an advantage for 'own' relative to similar exemplars
      characterized one of the two patients. Familiar home context had no impact on
      performance. The results suggest that repeated experience with personally
      familiar objects helps to maintain appropriate responses to them in the face of
      severely degraded conceptual knowledge.

PMID- 11997492
TI  - Sequencing and interleaving in routine action production.
AB  - We analysed the sequence of steps enacted during the performance of routine
      action tasks in the context of the 2 x 3 test. This test requires enactment of
      three routine tasks, each performed twice. Data from 35 healthy controls and 16
      closed head injury patients were analysed to derive 'modal routes' through the
      'sandwich', 'toast', and 'present' tasks, along with transition probabilities for
      the steps in the modal routes. Also investigated were the amount of interleaving
      and a potential structural constraint on interleaving. The results indicate that
      serial order production is more flexible than some might predict, and that the
      patients and controls were more similar than dissimilar on the measures taken.
      The first result argues against script architectures that are overly rigid. The
      second implies that the vulnerability to sequence and other errors in this
      patient group is not due to defects in script memories or serial order
      programming.

PMID- 11997493
TI  - Dissociations in routine behaviour across patients and everyday tasks.
AB  - We present a single case study of a patient, FK, who was severely impaired on
      routine, everyday tasks, such as preparing a cup of tea. We used the action
      coding system developed by Schwartz et al. to provide quantitative and
      qualitative measures of his performance in a number of experimental
      manipulations. In section A, we established FK's baseline performance on a range
      of tasks with (a) task-congruent objects only and (b) task-congruent objects and
      semantic distracters. In section B, we aimed to facilitate FK's performance by
      (a) giving him a pictorial representation of the goal, (b) giving him a set of
      written commands to follow, (c) giving him one command at a time, (d)
      demonstrating how the task should be performed and (e) dividing the task into
      smaller subgoals. We compared FK's performance with another patient, HG, to
      establish if there are qualitative differences between patients with 'action
      disorganization syndrome'. In section C, we aimed to hinder FK's performance by
      interrupting his execution of routine tasks. By comparing the factors that
      facilitated and impaired FK's performance in sections B and C, we hoped to
      isolate the key cognitive processes required to generate and control routine
      behaviour. In section D, we investigated how task demands impact on our ability
      to complete different everyday activities. The results of these experiments have
      important clinical implications for rehabilitation programmes for patients with
      action disorganization syndrome and can also help to distinguish between
      contemporary theoretical accounts of routine behaviour. In particular, we propose
      that patients who can be classified under the umbrella term of 'action
      disorganization syndrome' do not all have a reduction to 'non-specific cognitive
      resources' but can have qualitatively different impairments to a specialized
      action production system.

PMID- 11997494
TI  - How selenium has altered our understanding of the genetic code.

PMID- 11997495
TI  - Identification of novel isoforms of the BH3 domain protein Bim which directly
      activate Bax to trigger apoptosis.
AB  - Bim (Bcl-2-interacting mediator of cell death) is a member of the BH3 domain-only
      subgroup of Bcl-2 family members, for which three splice variants have been
      described. Bim is expressed in many healthy cell types, where it is maintained in
      an inactive conformation through binding to the microtubule-associated dynein
      motor complex. Upon certain apoptotic stimuli, Bim is released from microtubules
      and mediates caspase-dependent apoptosis through a mechanism that is still
      unclear. Here, we have identified and characterized novel splice variants of
      human Bim mRNA. In particular, we show that a newly discovered, small protein
      isoform, BimAD, is also able to induce apoptosis strongly in several human cell
      lines. BimAD and the previously characterized isoform BimS are shown to be
      capable of heterodimerizing in vivo with both death antagonists (Bcl-2 and Bcl
      X(L)) and death agonists (Bax). Mutants of BimAD that bind to Bax but not to Bcl
      2 still promote apoptosis, indicating that Bim can regulate apoptosis through
      direct activation of the Bax-mediated cell death pathway without interaction with
      antiapoptotic Bcl-2 family members. Furthermore, we have shown that the
      interaction of the BimS and BimAD isoforms with Bax leads to a conformational
      change in this protein analogous to that triggered by the BH3-only protein Bid.

PMID- 11997496
TI  - Antagonistic interactions between yeast [PSI(+)] and [URE3] prions and curing of
      [URE3] by Hsp70 protein chaperone Ssa1p but not by Ssa2p.
AB  - The yeast [PSI(+)], [URE3], and [PIN(+)] genetic elements are prion forms of
      Sup35p, Ure2p, and Rnq1p, respectively. Overexpression of Sup35p, Ure2p, or Rnq1p
      leads to increased de novo appearance of [PSI(+)], [URE3], and [PIN(+)],
      respectively. This inducible appearance of [PSI(+)] was shown to be dependent on
      the presence of [PIN(+)] or [URE3] or overexpression of other yeast proteins that
      have stretches of polar residues similar to the prion-determining domains of the
      known prion proteins. In a similar manner, [PSI(+)] and [URE3] facilitate the
      appearance of [PIN(+)]. In contrast to these positive interactions, here we find
      that in the presence of [PIN(+)], [PSI(+)] and [URE3] repressed each other's
      propagation and de novo appearance. Elevated expression of Hsp104 and Hsp70
      (Ssa2p) had little effect on these interactions, ruling out competition between
      the two prions for limiting amounts of these protein chaperones. In contrast, we
      find that constitutive overexpression of SSA1 but not SSA2 cured cells of [URE3],
      uncovering a specific interaction between Ssa1p and [URE3] and a functional
      distinction between these nearly identical Hsp70 isoforms. We also find that
      Hsp104 abundance, which critically affects [PSI(+)] propagation, is elevated when
      [URE3] is present. Our results are consistent with the notion that proteins that
      have a propensity to form prions may interact with heterologous prions but, as we
      now show, in a negative manner. Our data also suggest that differences in how
      [PSI(+)] and [URE3] interact with Hsp104 and Hsp70 may contribute to their
      antagonistic interactions.

PMID- 11997497
TI  - APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in
      response to insulin in 3T3-L1 adipocytes.
AB  - APS is a Cbl-binding protein that is tyrosine phosphorylated by the insulin
      receptor kinase. Insulin-stimulated phosphorylation of tyrosine 618 in APS is
      necessary for its association with c-Cbl and the subsequent tyrosine
      phosphorylation of Cbl by the insulin receptor in both 3T3-L1 adipocytes and CHO
      IR cells. When overexpressed in these cells, wild-type APS but not an APS/Y(618)F
      mutant facilitated the tyrosine phosphorylation of coexpressed Cbl and its
      association with Crk upon insulin stimulation. APS-facilitated phosphorylation
      occurred on tyrosines 371, 700, and 774 in the Cbl protein. APS also interacted
      directly with the c-Cbl-associated protein (CAP) and colocalized with the protein
      in cells. The association was dependent on the SH3 domains of CAP and was
      independent of insulin treatment. Overexpression of the APS/Y(618)F mutant in 3T3
      L1 adipocytes blocked the insulin-stimulated tyrosine phosphorylation of
      endogenous Cbl and binding to Crk. Moreover, the translocation of GLUT4 from
      intracellular vesicles to the plasma membrane was also inhibited by
      overexpression of the APS/Y(618)F mutant. These data suggest that APS serves as
      an adapter protein linking the CAP/Cbl pathway to the insulin receptor and,
      further, that APS-facilitated Cbl tyrosine phosphorylation catalyzed by the
      insulin receptor is a crucial event in the stimulation of glucose transport by
      insulin.

PMID- 11997498
TI  - mtCLIC/CLIC4, an organellular chloride channel protein, is increased by DNA
      damage and participates in the apoptotic response to p53.
AB  - mtCLIC/CLIC4 (referred to here as mtCLIC) is a p53- and tumor necrosis factor
      alpha-regulated cytoplasmic and mitochondrial protein that belongs to the CLIC
      family of intracellular chloride channels. mtCLIC associates with the inner
      mitochondrial membrane. Dual regulation of mtCLIC by two stress response pathways
      suggested that this chloride channel protein might contribute to the cellular
      response to cytotoxic stimuli. DNA damage or overexpression of p53 upregulates
      mtCLIC and induces apoptosis. Overexpression of mtCLIC by transient transfection
      reduces mitochondrial membrane potential, releases cytochrome c into the
      cytoplasm, activates caspases, and induces apoptosis. mtCLIC is additive with Bax
      in inducing apoptosis without a physical association of the two proteins.
      Antisense mtCLIC prevents the increase in mtCLIC levels and reduces apoptosis
      induced by p53 but not apoptosis induced by Bax, suggesting that the two
      proapoptotic proteins function through independent pathways. Our studies indicate
      that mtCLIC, like Bax, Noxa, p53AIP1, and PUMA, participates in a stress-induced
      death pathway converging on mitochondria and should be considered a target for
      cancer therapy through genetic or pharmacologic approaches.

PMID- 11997499
TI  - Synergy among nuclear receptor coactivators: selective requirement for protein
      methyltransferase and acetyltransferase activities.
AB  - Hormone-activated nuclear receptors (NR) bind to specific regulatory DNA elements
      associated with their target genes and recruit coactivator proteins to remodel
      chromatin structure, recruit RNA polymerase, and activate transcription. The p160
      coactivators (e.g., SRC-1, GRIP1, and ACTR) bind directly to activated NR and can
      recruit a variety of secondary coactivators. We have established a transient
      transfection assay system under which the activity of various NR is highly or
      completely dependent on synergistic cooperation among three classes of
      coactivators: a p160 coactivator, the protein methyltransferase CARM1, and any of
      the three protein acetyltransferases, p300, CBP, or p/CAF. The three-coactivator
      functional synergy was only observed when low levels of NR were expressed and was
      highly or completely dependent on the methyltransferase activity of CARM1 and the
      acetyltransferase activity of p/CAF, but not the acetyltransferase activity of
      p300. Other members of the protein arginine methyltransferase family, which
      methylate different protein substrates than CARM1, could not substitute for CARM1
      to act synergistically with p300 or p/CAF. A ternary complex of GRIP1, CARM1, and
      p300 or CBP was demonstrated in cultured mammalian cells, supporting a
      physiological role for the observed synergy. The transfection assay described
      here is a valuable new tool for investigating the mechanism of coactivator
      function and demonstrates the importance of multiple coactivators, including
      CARM1 and its specific protein methyltransferase activity, in transcriptional
      activation.

PMID- 11997500
TI  - Neutral sphingomyelinase 1 deficiency in the mouse causes no lipid storage
      disease.
AB  - Sphingomyelin is a major lipid in the bilayer of subcellular membranes of
      eukaryotic cells. Different sphingomyelinases catalyze the initial step in the
      catabolism of sphingomyelin, the hydrolysis to phosphocholine and ceramide.
      Sphingomyelinases have been postulated to generate ceramide as a lipophilic
      second messenger in intracellular signaling pathways involved in cell
      proliferation, differentiation, or apoptosis. To elucidate the function of the
      first cloned Mg(2+)-dependent, neutral sphingomyelinase (nSMase 1) in
      sphingomyelin catabolism and its potential role in signaling processes in a
      genetic and molecular approach, we have generated an nSMase 1-null mutant mouse
      line by gene targeting. The nSMase 1-deficient mice show an inconspicuous
      phenotype and no accumulation or changed metabolism of sphingomyelin or other
      lipids, despite grossly reduced nSMase activity in all organs except brain. We
      also addressed the recent proposal that nSMase 1 possesses lysophospholipase C
      activity. The unaltered metabolism of lysophosphatidylcholine or lyso-platelet
      activating factor excludes the proposed role of nSMase 1 as a lysophospholipase
      C.

PMID- 11997501
TI  - The adeno-associated virus type 2 Rep protein regulates RNA processing via
      interaction with the transcription template.
AB  - The adeno-associated virus type 2 (AAV) large Rep proteins can act to increase
      the ratio of spliced to unspliced AAV RNA when they are targeted to the
      transcription template via a Rep binding element. The required Rep binding site
      is both location and orientation independent; however, Rep enhancement decreases
      as the distance between the promoter and the intron of the affected transcription
      unit increases. Only the AAV intron and an extended polyadenylation site must
      remain for the AAV transcription unit to manifest responsiveness to Rep. A number
      of promoters, when driving the AAV capsid gene transcription unit, were
      responsive to targeted Rep, though to various degrees. Transactivation of
      transcription initiation is not sufficient for the enhancement of RNA processing,
      because activation of the P40 transcription unit by other activators targeted to
      this transcription template did not result in enhancement of the ratio of spliced
      to unspliced AAV RNA. These results suggest that Rep may act as a trans regulator
      of RNA processing by modulating such functions coupled to RNA polymerase II (RNA
      pol II) transcription, perhaps by affecting the composition of the transcription
      complex either prior to or during elongation. These results reveal another way in
      which gene expression can be regulated by trans-acting proteins and help explain
      an important feature of the parvovirus life cycle.

PMID- 11997502
TI  - Nucleosome remodeling by the human SWI/SNF complex requires transient global
      disruption of histone-DNA interactions.
AB  - We utilized a site-specific cross-linking technique to investigate the mechanism
      of nucleosome remodeling by hSWI/SNF. We found that a single cross-link between
      H2B and DNA virtually eliminates the accumulation of stably remodeled species as
      measured by restriction enzyme accessibility assays. However, cross-linking the
      histone octamer to nucleosomal DNA does not inhibit remodeling as monitored by
      DNase I digestion assays. Importantly, we found that the restriction enzyme
      accessible species can be efficiently cross-linked after remodeling and that the
      accessible state does not require continued ATP hydrolysis. These results imply
      that the generation of stable remodeled states requires at least transient
      disruption of histone-DNA interactions throughout the nucleosome, while hSWI/SNF
      catalyzed disruption of just local histone-DNA interactions yields less-stable
      remodeled states that still display an altered DNase I cleavage pattern. The
      implications of these results for models of the mechanism of SWI/SNF-catalyzed
      nucleosome remodeling are discussed.

PMID- 11997503
TI  - The transcription factor B-Myb is maintained in an inhibited state in target
      cells through its interaction with the nuclear corepressors N-CoR and SMRT.
AB  - The B-Myb transcription factor has been implicated in coordinating the expression
      of genes involved in cell cycle regulation. Although it is expressed in a
      ubiquitous manner, its transcriptional activity is repressed until the G(1)-S
      phase of the cell cycle by an unknown mechanism. In this study we used
      biochemical and cell-based assays to demonstrate that the nuclear receptor
      corepressors N-CoR and SMRT interact with B-Myb. The significance of these B-Myb
      corepressor interactions was confirmed by the finding that B-Myb mutants, which
      were unable to bind N-CoR, exhibited constitutive transcriptional activity. It
      has been shown previously that phosphorylation of B-Myb by cdk2/cyclin A enhances
      its transcriptional activity. We have now determined that phosphorylation by
      cdk2/cyclin A blocks the interaction between B-Myb and N-CoR and that mutation of
      the corepressor binding site within B-Myb bypasses the requirement for this
      phosphorylation event. Cumulatively, these findings suggest that the nuclear
      corepressors N-CoR and SMRT serve a previously unappreciated role as regulators
      of B-Myb transcriptional activity.

PMID- 11997504
TI  - B56-associated protein phosphatase 2A is required for survival and protects from
      apoptosis in Drosophila melanogaster.
AB  - Protein phosphorylation and specific protein kinases can initiate signal
      transduction pathways leading to programmed cell death. The specific protein
      phosphatases regulating apoptosis have been more elusive. Using double-stranded
      RNA-mediated interference (RNAi), the role of protein phosphatase 2A (PP2A) in
      cellular signaling was investigated. Knockdown of A or C subunits individually or
      of combined B subunits led to concurrent loss of nontargeted PP2A subunits,
      suggesting that PP2A is an obligate heterotrimer in vivo. Global knockdown of
      PP2A activity or specific loss of redundant B56 regulatory subunits caused cell
      death with the morphological and biochemical changes characteristic of apoptosis
      in cultured S2 cells. B56:PP2A-regulated apoptosis required caspases and the
      upstream regulators dark, reaper, head involution defective, and dp53. In
      Drosophila embryos, knockdown of B56-regulated PP2A activity resulted in
      apoptosis and failure of gastrulation, an effect that was blocked by concurrent
      RNAi of the caspase DRICE: B56-regulated PP2A activity appears to be required
      upstream of dp53 to maintain a critical proapoptotic substrate in a
      dephosphorylated, inactive state, thereby preventing apoptosis in Drosophila S2
      cells.

PMID- 11997505
TI  - ACK family tyrosine kinase activity is a component of Dcdc42 signaling during
      dorsal closure in Drosophila melanogaster.
AB  - We have characterized Drosophila melanogaster ACK (DACK), one of two members of
      the ACK family of nonreceptor tyrosine kinases in Drosophila. The ACKs are likely
      effectors for the small GTPase Cdc42, but signaling by these proteins remains
      poorly defined. ACK family tyrosine kinase activity functions downstream of
      Drosophila Cdc42 during dorsal closure of the embryo, as overexpression of DACK
      can rescue the dorsal closure defects caused by dominant-negative Dcdc42. Similar
      to known participants in dorsal closure, DACK is enriched in the leading edge
      cells of the advancing epidermis, but it does not signal through activation of
      the Jun amino-terminal kinase cascade operating in these cells. Transcription of
      DACK is responsive to changes in Dcdc42 signaling specifically at the leading
      edge and in the amnioserosa, two tissues involved in dorsal closure. Unlike other
      members of the ACK family, DACK does not contain a conserved Cdc42-binding motif,
      and transcriptional regulation may be one route by which Dcdc42 can affect DACK
      function. Expression of wild-type and kinase-dead DACK transgenes in embryos, and
      in the developing wing and eye, reveals that ACK family tyrosine kinase activity
      is involved in a range of developmental events similar to that of Dcdc42.

PMID- 11997506
TI  - Ligand-selective potentiation of rat mineralocorticoid receptor activation
      function 1 by a CBP-containing histone acetyltransferase complex.
AB  - The rat mineralocorticoid receptor (MR) has two activation functions in distinct
      regions of the A/B domain, designated activation function 1a (AF-1a; amino acids
      1 to 169) and AF-1b (amino acids 451 to 600). Since the p160 family protein TIF2,
      a known component of the AF-2 coactivator complex, potentiates the
      transactivation function of AF-1b but not that of AF-1a, it is likely that some
      other, novel protein complex interacts with the AF-1a region. Therefore, we
      attempted to identify such coactivator complexes from HeLa nuclear extracts by
      biochemical purification using a glutathione S-transferase-MR AF-1a fusion
      protein. Purified AF-1a region-interacting proteins were found to contain RNA
      helicase A (RHA) and CBP. Further analysis showed that RHA interacted with the AF
      1a region directly and then recruited a complex with histone acetyltransferase
      (HAT) activity that contained CBP. For full-length MR, aldosterone, but not
      hydrocortisone, was found to induce the binding of RHA/CBP complexes to the AF-1a
      region, as well as to allow the cooperative potentiation of MR transcriptional
      activity by RHA and CBP. In addition, a chromatin immunoprecipitation assay
      showed that aldosterone-bound MR, but not hydrocortisone-bound MR, recruited
      RHA/CBP complexes to native MR target gene promoters. Our results suggested that
      an altered conformation of the A/B region induced by aldosterone, but not
      hydrocortisone, might determine the accessibility of MR AF-1a to RHA/CBP
      complexes.

PMID- 11997507
TI  - tRNAs in Trypanosoma brucei: genomic organization, expression, and mitochondrial
      import.
AB  - The mitochondrial genome of Trypanosoma brucei does not encode tRNAs.
      Consequently, all mitochondrial tRNAs are imported from the cytosol and originate
      from nucleus-encoded genes. Analysis of all currently available T. brucei
      sequences revealed that its genome carries 50 tRNA genes representing 40
      different isoacceptors. The identified set is expected to be nearly complete
      since all but four codons are accounted for. The number of tRNA genes in T.
      brucei is very low for a eukaryote and lower than those of many prokaryotes.
      Using quantitative Northern analysis we have determined the absolute abundance in
      the cell and the mitochondrion of a group of 15 tRNAs specific for 12 amino
      acids. Except for the initiator type tRNA(Met), which is cytosol specific, the
      cytosolic and the mitochondrial sets of tRNAs were qualitatively identical.
      However, the extent of mitochondrial localization was variable for the different
      tRNAs, ranging from 1 to 7.5% per cell. Finally, by using transgenic cell lines
      in combination with quantitative Northern analysis it was shown that import of
      tRNA(Leu)(CAA) is independent of its 5'-genomic context, suggesting that the in
      vivo import substrate corresponds to the mature, fully processed tRNA.

PMID- 11997508
TI  - Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent
      mechanisms.
AB  - It is widely accepted that cyclic AMP (cAMP) can block cell growth by
      phosphorylating Raf-1 on serine 43 and inhibiting signaling to extracellular
      signal-regulated protein kinase. We show that the suppression of Raf-1 by cAMP is
      considerably more complex than previously reported. When cellular cAMP is
      elevated, Raf-1 is phosphorylated on three residues (S43, S233, and S259), which
      work independently to block Raf-1. Both Ras-dependent and Ras-independent
      processes are disrupted. However, when cAMP-insensitive versions of Raf-1 are
      expressed in NIH 3T3 cells, their growth is still strongly suppressed when cAMP
      is elevated. Thus, although Raf-1 appears to be an important cAMP target, other
      pathways are also targeted by cAMP, providing alternative mechanisms that lead to
      suppression of cell growth.

PMID- 11997509
TI  - Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein
      PU.1.
AB  - Aberrant expression of PU.1 inhibits erythroid cell differentiation and
      contributes to the formation of murine erythroleukemias (MEL). The molecular
      mechanism by which this occurs is poorly understood. Here we show that PU.1
      specifically and efficiently inhibits CBP-mediated acetylation of several nuclear
      proteins, including the hematopoietic transcription factors GATA-1, NF-E2, and
      erythroid Kruppel-like factor. In addition, PU.1 blocks acetylation of histones
      and interferes with acetylation-dependent transcriptional events. CBP
      acetyltransferase activity increases during MEL cell differentiation as PU.1
      levels decline and is inhibited by sustained PU.1 expression. Finally, PU.1
      inhibits the differentiation-associated increase in histone acetylation at an
      erythroid-specific gene locus in vivo. Together, these findings suggest that
      aberrant expression of PU.1 and possibly other members of the Ets family of
      oncoproteins subverts normal cellular differentiation in part by inhibiting the
      acetylation of critical nuclear factors involved in balancing cellular
      proliferation and maturation.

PMID- 11997510
TI  - Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding
      protein during monocyte/macrophage differentiation.
AB  - Mona/Gads is a Grb2-related, Src homology 3 (SH3) and SH2 domain-containing
      adapter protein whose expression is restricted to cells of hematopoietic lineage
      (i.e., monocytes and T lymphocytes). During monocyte/macrophage differentiation,
      Mona is induced and interacts with the macrophage colony-stimulating factor
      receptor, M-CSFR (also called Fms), suggesting that Mona could be involved in
      developmental signaling downstream of the M-CSFR by recruiting additional
      signaling proteins to the activated receptor. Our present results identify Mona
      as a specific partner protein for the DOS/Gab family member Gab3 in
      monocytic/macrophage development. Mona does not interact with Gab2; however, Gab3
      also forms a complex with the Mona-related adapter Grb2. Glutathione S
      transferase pull-down experiments demonstrate that the Mona and Gab3 interaction
      utilizes the carboxy-terminal SH3 domain of Mona and the atypical proline-rich
      domain of Gab3. Mona is known to interact with the phosphorylated Y697 site of
      the M-CSFR. The M-CSFR mutation Y697F exhibited qualitative and quantitative
      abnormalities in receptor and Gab3 tyrosine phosphorylation, and Mona induction
      was greatly reduced. The Y807F M-CSFR mutation is defective in differentiation
      signaling, but not growth signaling, and also fails to induce Mona protein
      expression. During M-CSF-stimulated macrophage differentiation of mouse bone
      marrow cells, Mona and Gab3 expression is coinduced, these proteins interact, and
      Mona engages in multimolecular complexes. These data suggest that association of
      Mona and Gab3 plays a specific role in mediating the M-CSFR differentiation
      signal.

PMID- 11997511
TI  - CK2 forms a stable complex with TFIIIB and activates RNA polymerase III
      transcription in human cells.
AB  - CK2 is a highly conserved protein kinase with growth-promoting and oncogenic
      properties. It is known to activate RNA polymerase III (PolIII) transcription in
      Saccharomyces cerevisiae and is shown here to also exert a potent effect on
      PolIII in mammalian cells. Peptide and chemical inhibitors of CK2 block PolIII
      transcription in human cell extracts. Furthermore, PolIII transcription in
      mammalian fibroblasts is decreased significantly when CK2 activity is compromised
      by chemical inhibitors, antisense oligonucleotides, or kinase-inactive mutants.
      Coimmunoprecipitation and cofractionation show that endogenous human CK2
      associates stably and specifically with the TATA-binding protein-containing
      factor TFIIIB, which brings PolIII to the initiation site of all class III genes.
      Serum stimulates TFIIIB phosphorylation in vivo, an effect that is diminished by
      inhibitors of CK2. Binding to TFIIIC2 recruits TFIIIB to most PolIII promoters;
      this interaction is compromised specifically by CK2 inhibitors. The data suggest
      that CK2 stimulates PolIII transcription by binding and phosphorylating TFIIIB
      and facilitating its recruitment by TFIIIC2. CK2 also activates PolI
      transcription in mammals and may therefore provide a mechanism to coregulate the
      output of PolI and PolIII. CK2 provides a rare example of an endogenous activity
      that operates on the PolIII system in both mammals and yeasts. Such evolutionary
      conservation suggests that this control may be of fundamental importance.

PMID- 11997512
TI  - Paip1 interacts with poly(A) binding protein through two independent binding
      motifs.
AB  - The 3' poly(A) tail of eukaryotic mRNAs plays an important role in the regulation
      of translation. The poly(A) binding protein (PABP) interacts with eukaryotic
      initiation factor 4G (eIF4G), a component of the eIF4F complex, which binds to
      the 5' cap structure. The PABP-eIF4G interaction brings about the circularization
      of the mRNA by joining its 5' and 3' termini, thereby stimulating mRNA
      translation. The activity of PABP is regulated by two interacting proteins, Paip1
      and Paip2. To study the mechanism of the Paip1-PABP interaction, far-Western,
      glutathione S-transferase pull-down, and surface plasmon resonance experiments
      were performed. Paip1 contains two binding sites for PABP, PAM1 and PAM2 (for
      PABP-interacting motifs 1 and 2). PAM2 consists of a 15-amino-acid stretch
      residing in the N terminus, and PAM1 encompasses a larger C-terminal acidic-amino
      acid-rich region. PABP also contains two Paip1 binding sites, one located in RNA
      recognition motifs 1 and 2 and the other located in the C-terminal domain. Paip1
      binds to PABP with a 1:1 stoichiometry and an apparent K(d) of 1.9 nM.

PMID- 11997513
TI  - Critical role of diacylglycerol- and phospholipid-regulated protein kinase C
      epsilon in induction of low-density lipoprotein receptor transcription in
      response to depletion of cholesterol.
AB  - Induction of low-density lipoprotein (LDL) receptor transcription in response to
      depletion of cellular sterols in animal cells is well established. The
      intracellular signal or signals involved in regulating this process, however,
      remain unknown. Using a specific inhibitor of protein kinase C (PKC), calphostin
      C, we show the requirement of this kinase in the induction process in human
      hepatoma HepG2 cells. Overexpression of PKC epsilon, but not PKC alpha, -gamma, 
      delta, or -zeta was found to dramatically induce (approximately 18-fold) LDL
      receptor promoter activity. Interestingly, PKC epsilon-mediated induction was
      found to be sterol resistant. To further establish that PKC epsilon is involved
      in the sterol regulation of LDL receptor gene transcription, endogenous PKC
      epsilon was specifically inhibited by transfection with antisense PKC epsilon
      phosphorothionate oligonucleotides. Antisense treatment decreased endogenous PKC
      epsilon protein levels and completely blocked induction of LDL receptor
      transcription following sterol depletion. PKC epsilon-induced LDL receptor
      transcription is independent of the extracellular signal-regulated kinase 1 and 2
      (p42/44(MAPK)) cascade, because the MEK-1/2 inhibitor, PD98059 did not inhibit,
      even though it blocked p42/44(MAPK) activation. Finally, photoaffinity labeling
      studies showed an isoform-specific interaction between PKC epsilon and sterols,
      suggesting that sterols may directly modulate its function by hampering binding
      of activators. This was confirmed by PKC activity assays. Altogether, these
      results define a novel signaling pathway leading to induction of LDL receptor
      transcription following sterol depletion, and a model is proposed to account for
      a new function for PKC epsilon as part of a sterol-sensitive signal transduction
      pathway in hepatic cells.

PMID- 11997514
TI  - Growth and early postimplantation defects in mice deficient for the bromodomain
      containing protein Brd4.
AB  - In a gene trap screen we recovered a mouse mutant line in which an insertion
      generated a null allele of the Brd4 gene. Brd4 belongs to the Fsh/Brd family, a
      group of structurally related proteins characterized by the association of two
      bromodomains and one extraterminal domain. Members of this family include
      Brd2/Ring3/Fsrg1 in mammals, fs(1)h in Drosophila, and Bdf1 in Saccharomyces
      cerevisiae. Brd4 heterozygotes display pre- and postnatal growth defects
      associated with a reduced proliferation rate. These mice also exhibit a variety
      of anatomical abnormalities: head malformations, absence of subcutaneous fat,
      cataracts, and abnormal liver cells. In primary cell cultures, heterozygous cells
      also display reduced proliferation rates and moderate sensitivity to methyl
      methanesulfonate. Embryos nullizygous for Brd4 die shortly after implantation and
      are compromised in their ability to maintain an inner cell mass in vitro,
      suggesting a role in fundamental cellular processes. Finally, sequence
      comparisons suggest that Brd4 is likely to correspond to the Brd-like element of
      the mediator of transcriptional regulation isolated by Y. W. Jiang, P.
      Veschambre, H. Erdjument-Bromage, P. Tempst, J. W. Conaway, R. C. Conaway, and R.
      D. Kornberg (Proc. Natl. Acad. Sci. USA 95:8538-8543, 1998) and the Brd4 mutant
      phenotype is discussed in light of this result. Together, our results provide the
      first genetic evidence for an in vivo role in mammals for a member of the Fsh/Brd
      family.

PMID- 11997515
TI  - Desumoylation activity of Axam, a novel Axin-binding protein, is involved in
      downregulation of beta-catenin.
AB  - Axam has been identified as a novel Axin-binding protein that inhibits the Wnt
      signaling pathway. We studied the molecular mechanism by which Axam stimulates
      the downregulation of beta-catenin. The C-terminal region of Axam has an amino
      acid sequence similar to that of the catalytic region of SENP1, a SUMO-specific
      protease (desumoylation enzyme). Indeed, Axam exhibited activity to remove SUMO
      from sumoylated proteins in vitro and in intact cells. The Axin-binding domain is
      located in the central region of Axam, which is different from the catalytic
      domain. Neither the Axin-binding domain nor the catalytic domain alone was
      sufficient for the downregulation of beta-catenin. An Axam fragment which
      contains both domains was able to decrease the level of beta-catenin. On
      substitution of Ser for Cys(547) in the catalytic domain, Axam lost its
      desumoylation activity. Further, this Axam mutant decreased the activity to
      downregulate beta-catenin. Although Axam strongly inhibited axis formation and
      expression of siamois, a Wnt-response gene, in Xenopus embryos, Axam(C547S)
      showed weak activities. These results demonstrate that Axam functions as a
      desumoylation enzyme to downregulate beta-catenin and suggest that sumoylation is
      involved in the regulation of the Wnt signaling pathway.

PMID- 11997516
TI  - Conserved CTCF insulator elements flank the mouse and human beta-globin loci.
AB  - A binding site for the transcription factor CTCF is responsible for enhancer
      blocking activity in a variety of vertebrate insulators, including the insulators
      at the 5' and 3' chromatin boundaries of the chicken beta-globin locus. To date,
      no functional domain boundaries have been defined at mammalian beta-globin loci,
      which are embedded within arrays of functional olfactory receptor genes. In an
      attempt to define boundary elements that could separate these gene clusters, CTCF
      binding sites were searched for at the most distal DNase I-hypersensitive sites
      (HSs) of the mouse and human beta-globin loci. Conserved CTCF sites were found at
      5'HS5 and 3'HS1 of both loci. All of these sites could bind to CTCF in vitro. The
      sites also functioned as insulators in enhancer-blocking assays at levels
      correlating with CTCF-binding affinity, although enhancer-blocking activity was
      weak with the mouse 5'HS5 site. These results show that with respect to enhancer
      blocking elements, the architecture of the mouse and human beta-globin loci is
      similar to that found previously for the chicken beta-globin locus. Unlike the
      chicken locus, the mouse and human beta-globin loci do not have nearby
      transitions in chromatin structure but the data suggest that 3'HS1 and 5'HS5 may
      function as insulators that prevent inappropriate interactions between beta
      globin regulatory elements and those of neighboring domains or subdomains, many
      of which possess strong enhancers.

PMID- 11997517
TI  - The acetyltransferase activity of CBP is required for wingless activation and H4
      acetylation in Drosophila melanogaster.
AB  - CBP is a critical coactivator of transcription, but little is understood about
      the importance of its intrinsic acetyltransferase (AT) activity in gene
      activation in vivo. We show that the intrinsic AT function of CBP in Drosophila
      melanogaster (dCBP) is necessary to maintain a dCBP overexpression phenotype in
      the eye, for the in vivo activation of a specific target gene, wingless, and for
      the global acetylation of histone H4. These findings indicate that a point
      mutation which alters the intrinsic AT activity of CBP (only one of many CBP
      functions) has profound effects on CBP-induced gene activation in a
      physiologically intact transcription system. Furthermore, the effects of CBP AT
      activity are not limited to a few specific promoters, but rather CBT AT activity
      may play a role in regulating global histone acetylation throughout the
      developing organism.

PMID- 11997518
TI  - Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis.
AB  - PTEN is mutated at high frequency in many primary human cancers and several
      familial cancer predisposition disorders. Activation of AKT is a common event in
      tumors in which the PTEN gene has been inactivated. We previously showed that
      deletion of the murine Pten gene in embryonic stem (ES) cells led to increased
      phosphatidylinositol triphosphate (PIP(3)) accumulation, enhanced entry into S
      phase, and better cell survival. Since PIP(3) controls multiple signaling
      molecules, it was not clear to what degree the observed phenotypes were due to
      deregulated AKT activity. In this study, we mutated Akt-1 in Pten(-/-) ES cells
      to directly assess the role of AKT-1 in PTEN-controlled cellular processes, such
      as cell proliferation, cell survival, and tumorigenesis in nude mice. We showed
      that AKT-1 is one of the major downstream effectors of PTEN in ES cells and that
      activation of AKT-1 is required for both the cell survival and cell proliferation
      phenotypes observed in Pten(-/-) ES cells. Deletion of Akt-1 partially reverses
      the aggressive growth of Pten(-/-) ES cells in vivo, suggesting that AKT-1 plays
      an essential role in PTEN-controlled tumorigenesis.

PMID- 11997519
TI  - Strand bias in targeted gene repair is influenced by transcriptional activity.
AB  - Modified single-stranded DNA oligonucleotides can direct nucleotide exchange in
      Saccharomyces cerevisiae. Point and frameshift mutations are corrected in a
      reaction catalyzed by cellular enzymes involved in various DNA repair processes.
      The present model centers on the annealing of the vector to one strand of the
      helix, followed by the correction of the designated base. The choice of which
      strand to target is a reaction parameter that can be controlled, so here we
      investigate the properties of strand bias in targeted gene repair. An in vivo
      system has been established in which a plasmid containing an actively
      transcribed, but mutated, hygromycin-enhanced green fluorescent protein fusion
      gene is targeted for repair and upon conversion will confer hygromycin resistance
      on the cell. Overall transcriptional activity has a positive influence on the
      reaction, elevating the frequency. If the targeting vector is synthesized so that
      it directs nucleotide repair on the nontranscribed strand, the level of gene
      repair is higher than if the template strand is targeted. We provide data showing
      that the targeting vector can be displaced from the template strand by an active
      T7 phage RNA polymerase. The strand bias is not influenced by which strand serves
      as the leading or lagging strand during DNA synthesis. These results may provide
      an explanation for the enhancement of gene repair observed when the non-template
      strand is targeted.

PMID- 11997520
TI  - The PERK eukaryotic initiation factor 2 alpha kinase is required for the
      development of the skeletal system, postnatal growth, and the function and
      viability of the pancreas.
AB  - Phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) is
      typically associated with stress responses and causes a reduction in protein
      synthesis. However, we found high phosphorylated eIF-2 alpha (eIF-2 alpha[P])
      levels in nonstressed pancreata of mice. Administration of glucose stimulated a
      rapid dephosphorylation of eIF-2 alpha. Among the four eIF-2 alpha kinases
      present in mammals, PERK is most highly expressed in the pancreas, suggesting
      that it may be responsible for the high eIF-2 alpha[P] levels found therein. We
      describe a Perk knockout mutation in mice. Pancreata of Perk(-/-) mice are
      morphologically and functionally normal at birth, but the islets of Langerhans
      progressively degenerate, resulting in loss of insulin-secreting beta cells and
      development of diabetes mellitus, followed later by loss of glucagon-secreting
      alpha cells. The exocrine pancreas exhibits a reduction in the synthesis of
      several major digestive enzymes and succumbs to massive apoptosis after the
      fourth postnatal week. Perk(-/-) mice also exhibit skeletal dysplasias at birth
      and postnatal growth retardation. Skeletal defects include deficient
      mineralization, osteoporosis, and abnormal compact bone development. The skeletal
      and pancreatic defects are associated with defects in the rough endoplasmic
      reticulum of the major secretory cells that comprise the skeletal system and
      pancreas. The skeletal, pancreatic, and growth defects are similar to those seen
      in human Wolcott-Rallison syndrome.

PMID- 11997521
TI  - Role of SHP-2 in fibroblast growth factor receptor-mediated suppression of
      myogenesis in C2C12 myoblasts.
AB  - Ligand activation of the fibroblast growth factor receptor (FGFR) represses
      myogenesis and promotes activation of extracellular signal-regulated kinases 1
      and 2 (Erks). The precise mechanism through which the FGFR transmits both of
      these signals in myoblasts remains unclear. The SH2 domain-containing protein
      tyrosine phosphatase, SHP-2, has been shown to participate in the regulation of
      FGFR signaling. However, no role for SHP-2 in FGFR myogenic signaling is known.
      In this study, we show that stimulation of C2C12 myoblasts with FGF-2 induces SHP
      2 complex formation with tyrosyl-phosphorylated FGFR substrate 2 alpha (FRS-2
      alpha). Both the catalytic activity and, to a much lesser extent, the Grb2
      binding-tyrosyl phosphorylation sites of SHP-2 are required for maximal FGF-2
      induced Erk activity and Elk-1 transactivation. When overexpressed in C2C12
      myoblasts, wild-type SHP-2, but not a catalytically inactive SHP-2 mutant,
      potentiates the suppressive effects of FGF-2 on muscle-specific gene expression.
      In addition, expression of a constitutively active mutant of SHP-2 is sufficient
      to prevent myogenesis. The constitutively active mutant of SHP-2 induces hyper
      tyrosyl phosphorylation of FRS-2 alpha but fails to stimulate or potentiate
      either FGF-2-induced Erk activation or Elk-1 transactivation. These data suggest
      that in myoblasts, SHP-2 represses myogenesis via a pathway that is independent
      of the Erks. We propose that SHP-2 plays a pivotal role in FGFR signaling in
      myoblasts via both Erk-dependent and Erk-independent pathways.

PMID- 11997522
TI  - Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases.
AB  - Nuclear factor of activated T cells (NFAT) is implicated in multiple biological
      processes, including cytokine gene expression, cardiac hypertrophy, and adipocyte
      differentiation. A conserved NFAT homology domain is identified in all NFAT
      members. Dephosphorylation of the NFAT homology region is critical for NFAT
      nuclear translocation and transcriptional activation. Here we demonstrate that
      NFATc4 is phosphorylated by p38 mitogen-activated protein (MAP) kinase but not by
      JNK. The p38 MAP kinase phosphorylates multiple residues, including Ser(168) and
      Ser(170), in the NFAT homology domain of NFATc4. Replacement of Ser(168,170) with
      Ala promotes nuclear localization of NFATc4 and increases NFAT-mediated
      transcription activity. Stable expression of Ala(168,170) NFATc4, but not of wild
      type NFATc4, in NIH 3T3 cells promotes adipocyte formation under differentiation
      conditions. Molecular analysis indicates that peroxisome proliferator-activated
      receptor gamma 2 (PPAR gamma 2) is a target of NFAT. Two distinct NFAT binding
      elements are located in the PPAR gamma 2 gene promoter. Stable expression of
      Ala(168,170) NFATc4, but not of wild-type NFATc4, increases the expression of
      PPAR gamma, which contributes in part to increased adipocyte formation. Thus,
      NFAT regulates PPAR gamma gene expression and has a direct role in adipocyte
      differentiation.

PMID- 11997523
TI  - Intracellular retention of glycosylphosphatidyl inositol-linked proteins in
      caveolin-deficient cells.
AB  - The relationship between glycosylphosphatidyl inositol (GPI)-linked proteins and
      caveolins remains controversial. Here, we derived fibroblasts from Cav-1 null
      mouse embryos to study the behavior of GPI-linked proteins in the absence of
      caveolins. These cells lack morphological caveolae, do not express caveolin-1,
      and show a approximately 95% down-regulation in caveolin-2 expression; these
      cells also do not express caveolin-3, a muscle-specific caveolin family member.
      As such, these caveolin-deficient cells represent an ideal tool to study the role
      of caveolins in GPI-linked protein sorting. We show that in Cav-1 null cells GPI
      linked proteins are preferentially retained in an intracellular compartment that
      we identify as the Golgi complex. This intracellular pool of GPI-linked proteins
      is not degraded and remains associated with intracellular lipid rafts as judged
      by its Triton insolubility. In contrast, GPI-linked proteins are transported to
      the plasma membrane in wild-type cells, as expected. Furthermore, recombinant
      expression of caveolin-1 or caveolin-3, but not caveolin-2, in Cav-1 null cells
      complements this phenotype and restores the cell surface expression of GPI-linked
      proteins. This is perhaps surprising, as GPI-linked proteins are confined to the
      exoplasmic leaflet of the membrane, while caveolins are cytoplasmically oriented
      membrane proteins. As caveolin-1 normally undergoes palmitoylation on three
      cysteine residues (133, 143, and 156), we speculated that palmitoylation might
      mechanistically couple caveolin-1 to GPI-linked proteins. In support of this
      hypothesis, we show that palmitoylation of caveolin-1 on residues 143 and 156,
      but not residue 133, is required to restore cell surface expression of GPI-linked
      proteins in this complementation assay. We also show that another lipid raft
      associated protein, c-Src, is retained intracellularly in Cav-1 null cells. Thus,
      Golgi-associated caveolins and caveola-like vesicles could represent part of the
      transport machinery that is necessary for efficiently moving lipid rafts and
      their associated proteins from the trans-Golgi to the plasma membrane. In further
      support of these findings, GPI-linked proteins were also retained intracellularly
      in tissue samples derived from Cav-1 null mice (i.e., lung endothelial and renal
      epithelial cells) and Cav-3 null mice (skeletal muscle fibers).

PMID- 11997524
TI  - Characterization of a high-molecular-weight Notch complex in the nucleus of
      Notch(ic)-transformed RKE cells and in a human T-cell leukemia cell line.
AB  - Notch genes encode a family of transmembrane proteins that are involved in many
      cellular processes, such as differentiation, proliferation, and apoptosis. It is
      well established that all four Notch genes can act as oncogenes; however, the
      mechanism by which Notch proteins transform cells remains unknown. Previously, we
      reported that both nuclear localization and transcriptional activation are
      required for neoplastic transformation of RKE cells. Furthermore, we identified
      cyclin D1 as a direct transcriptional target of constitutively active Notch
      molecules. In an effort to understand the mechanism by which Notch functions in
      the nucleus, we sought to determine if Notch formed stable complexes using size
      exclusion chromatography. Herein, we report that the Notch intracellular domain
      (N(ic)) forms distinct high-molecular-weight complexes in the nuclei of
      transformed RKE cells. The largest complex is approximately 1.5 MDa and contains
      both endogenous CSL (for CBF1, Suppressor of Hairless, and Lag-1) and Mastermind
      Like-1 (Maml). N(ic) molecules that do not have the high-affinity binding site
      for CSL (RAM) retain the ability to associate with CSL in a stable complex
      through interactions involving Maml. However, Maml does not directly bind to CSL.
      Furthermore, Maml can rescue Delta RAM transcriptional activity on a CSL
      dependent promoter. These results indicate that deletion of the RAM domain does
      not equate to CSL-independent signaling. Moreover, in SUP-T1 cells, N(ic) exists
      exclusively in the largest N(ic)-containing complex. SUP-T1 cells are derived
      from a T-cell leukemia that harbors the t(7;9)(q34;q34.3) translocation and
      constitutively express N(ic). Taken together, our data indicate that complex
      formation is likely required for neoplastic transformation by Notch(ic).

PMID- 11997526
TI  - RSNA Board of Directors develops a 3-year strategic plan.

PMID- 11997527
TI  - Marie Sklodowska Curie in America, 1921.

PMID- 11997525
TI  - A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune
      defense and is induced by the v-Rel oncoprotein.
AB  - The cloning and functional characterization of a novel interferon regulatory
      factor (IRF), IRF-10, are described. IRF-10 is most closely related to IRF-4 but
      differs in both its constitutive and inducible expression. The expression of IRF
      10 is inducible by interferons (IFNs) and by concanavalin A. In contrast to that
      of other IRFs, the inducible expression of IRF-10 is characterized by delayed
      kinetics and requires protein synthesis, suggesting a unique role in the later
      stages of an antiviral defense. Accordingly, IRF-10 is involved in the
      upregulation of two primary IFN-gamma target genes (major histocompatibility
      complex [MHC] class I and guanylate-binding protein) and interferes with the
      induction of the type I IFN target gene for 2',5'-oligo(A) synthetase. IRF-10
      binds the interferon-stimulated response element site of the MHC class I
      promoter. In contrast to that of IRF-1, which has some of the same functional
      characteristics, the expression of IRF-10 is not cytotoxic for fibroblasts or B
      cells. The expression of IRF-10 is induced by the oncogene v-rel, the proto
      oncogene c-rel, and IRF-4 in a tissue-specific manner. Moreover, v-Rel and IRF-4
      synergistically cooperate in the induction of IRF-10 in fibroblasts. The level of
      IRF-10 induction in lymphoid cell lines by Rel proteins correlates with Rel
      transformation potential. These results suggest that IRF-10 plays a role in the
      late stages of an immune defense by regulating the expression some of the IFN
      gamma target genes in the absence of a cytotoxic effect. Furthermore, IRF-10
      expression is regulated, at least in part, by members of the Rel/NF-kappa B and
      IRF families.

PMID- 11997529
TI  - Radiologic research: the residents' perspective.

PMID- 11997528
TI  - Comparison of techniques for image-guided ablation of focal liver tumors.

PMID- 11997530
TI  - Are gadolinium-based contrast media really safer than iodinated media for digital
      subtraction angiography in patients with azotemia?
AB  - Gadolinium chelates, intended as intravenous contrast media for magnetic
      resonance imaging, have been regarded as nonnephrotoxic and recommended to
      replace iodinated contrast media in patients with azotemia who are undergoing
      digital subtraction angiography (DSA). High intraarterial doses (up to 220 mmol
      of gadodiamide) have been used, with a 40% incidence of nephropathy. The authors
      discourage the use of gadolinium for DSA for several reasons. (a) There exist no
      randomized studies comparing the nephrotoxic effects of gadolinium-based and
      iodinated media at equal-attenuating concentrations and doses. (b) Gadolinium
      based media are hypertonic, a pathogenetic factor in contrast medium-induced
      nephropathy after renal angiography, with an osmolality two to seven times that
      of plasma. Iodinated media in concentrations that are equally attenuating with
      gadolinium-based media can be made isotonic. (c) In vitro measurements indicate
      that 0.5 mol/L gadolinium chelates are equally attenuating with 60-80 mg iodine
      per milliliter at the commonly used 70-90-kV range used for DSA. Thus, 50 mL of
      0.5 mol/L gadolinium chelate ( approximately 0.3 mmol/kg in an 80-kg person)
      would be equally attenuating with a dose of 3-4 g of iodine in an iodinated
      medium (eg, 50 mL iohexol at 60-80 mg I/mL or 10-13 mL at 300 mg I/mL). (d) By
      combining these data on attenuation and results of toxicity studies in mice, the
      general toxicity of gadolinium chelates may be six to 25 times higher than that
      of equal-attenuating doses of iodinated media at 70-kV DSA. Thus, the authors
      believe that at equal-attenuating doses for DSA, modern iodinated contrast media
      should result in a lower toxic load on the body than with presently available
      gadolinium chelates.

PMID- 11997531
TI  - Gadolinium chelates in angiography and interventional radiology: a useful
      alternative to iodinated contrast media for angiography.
AB  - Gadolinium has physical properties that are well suited for radiographic imaging.
      Digital subtraction angiography with a gadolinium chelate as contrast medium can
      provide images of suitable quality for diagnosis and intervention. The overall
      safety profile of gadolinium-based contrast media is excellent. In particular,
      these contrast media are well tolerated in patients with renal insufficiency when
      administered intraarterially in doses of less than 0.3-0.4 mmol per kilogram body
      weight, with a decreased incidence of contrast medium-induced nephropathy, as
      compared with similar volumes of iodinated contrast material. The currently
      available formulations of gadolinium chelates can be injected safely into every
      arterial and venous structure. However, substantial data are lacking on the
      intraarterial use of gadolinium in patients with renal insufficiency,
      particularly at doses that exceed those routinely used in magnetic resonance
      angiography. Gadolinium chelates in appropriate volumes are useful alternative
      contrast media in selected high-risk patients undergoing angiographic studies.

PMID- 11997534
TI  - Small hepatocellular carcinoma: comparison of radio-frequency ablation and
      percutaneous microwave coagulation therapy.
AB  - PURPOSE: To evaluate the effectiveness of radio-frequency (RF) ablation and
      percutaneous microwave coagulation (PMC) for treatment of hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Seventy-two patients with 94 HCC nodules
      were randomly assigned to RF ablation and PMC groups. Thirty-six patients with 48
      nodules were treated with RF ablation, and 36 patients with 46 nodules were
      treated with PMC. Therapeutic effect, residual foci of untreated disease, and
      complications of RF ablation and PMC were prospectively evaluated with
      statistical analyses. RESULTS: The number of treatment sessions per nodule was
      significantly lower in the RF ablation group than in the PMC group (1.1 vs 2.4; P
      <.001). Complete therapeutic effect was achieved in 46 (96%) of 48 nodules
      treated with RF ablation and in 41 (89%) of 46 nodules treated with PMC (P =.26).
      Major complications occurred in one patient treated with RF ablation and in four
      patients treated with PMC (P =.36). During follow-up (range, 6-27 months),
      residual foci of untreated disease were seen in four of 48 nodules treated with
      RF ablation and in eight of 46 nodules treated with PMC. No significant
      difference in rates of residual foci of untreated disease was noted (P =.20, log
      rank test). CONCLUSION: RF ablation and PMC thus far have had equivalent
      therapeutic effects, complication rates, and rates of residual foci of untreated
      disease. However, RF tumor ablation can be achieved with fewer sessions.

PMID- 11997535
TI  - Restoration of thrombosed Brescia-Cimino dialysis fistulas by using percutaneous
      transluminal angioplasty.
AB  - PURPOSE: To evaluate the authors' experience with a technique for management of
      thrombosed Brescia-Cimino arteriovenous fistula. MATERIALS AND METHODS: Forty
      patients with 42 thrombosed arteriovenous fistulas were percutaneously treated.
      Thrombosis occurred within 24 hours of attempted angioplasty in five fistulas,
      between 24 and 72 hours in 27, and longer than 72 hours in 10. Thrombosed
      fistulas were approached in a retrograde fashion followed by direct balloon
      dilation with 5-8-mm balloon catheters. If retrograde catheterization failed to
      cross the arterial anastomosis, an antegrade puncture directly into the
      thrombosed drainage vein close to the anastomosis was performed with
      ultrasonographic guidance, as an aid to catheterize the arterial inflow.
      Thrombolytic therapy with infusion of urokinase directly into the thrombus was
      performed in selected patients with visible thrombus that had compromised blood
      flow in the partially restored vascular access. Postintervention primary and
      secondary patency was calculated by using Kaplan-Meier analysis. Patency rates
      between patients without and with urokinase infusion were examined by using the
      log-rank test. RESULTS: Anatomic success was achieved in 39 (93%) of 42 fistulas;
      and clinical patency, in 38 (90%) of 42 fistulas. Postintervention primary and
      secondary patencies (including initial technical failure) at 6, 12, and 18 months
      were 81% and 84%, 70% and 80%, and 63% and 80%, respectively. No significance of
      patency rate between patients without and with urokinase infusion was found (P
      =.912). Three patients died of unrelated causes at 1, 2, and 5 months after the
      procedures. No major complications were encountered. CONCLUSION: High anatomic
      success and excellent clinical patency can be achieved in the salvage of
      thrombosed arteriovenous fistulas. Percutaneous restoration of arteriovenous
      fistulas should be attempted before surgical recreation to optimize outcome in
      patients undergoing hemodialysis.

PMID- 11997536
TI  - Femoropopliteal arteries: immediate and long-term results with a Dacron-covered
      stent-graft.
AB  - PURPOSE: To assess immediate and long-term outcome after femoropopliteal
      implantation of a Dacron-covered stent-graft in patients with peripheral arterial
      disease. MATERIALS AND METHODS: This prospective cohort study included 30
      consecutive patients who underwent Dacron-covered stent-graft implantation
      because of recurrent stenosis after percutaneous transluminal angioplasty in the
      femoropopliteal segment. After interventional treatment, 100 mg of
      acetylsalicylic acid daily and oral anticoagulation therapy (therapeutic level,
      international normalized ratio, 2.0-3.0) were administered. Patients were
      followed up with ankle-brachial index measurement, color-coded duplex
      ultrasonography, and angiography. Primary and secondary patency rates and
      postintervention complications were documented as was initial technical success.
      Kaplan-Meier and life table analyses were used for calculation of patency rates.
      RESULTS: Initial technical success was achieved in all 30 patients, with
      significant improvement of ankle-brachial index from a preintervention mean of
      0.5 +/- 0.14 (SD) to a postintervention mean of 0.8 +/- 0.17 (P <.001).
      Postimplantation noninfectious fever and leukocyte and C-reactive protein level
      elevation occurred in 12 patients (40%), and 17 patients (57%) reported
      persistent pain at the site of implantation for a mean of 5 days (range, 2-28
      days). Early recurrent occlusion within the first 24 hours was found in five
      patients (17%). Within the mean follow-up period of 60 months +/- 10, restenosis
      occurred in 25 patients (83%). At 6, 12, 36, and 72 months, respectively, primary
      patency rates were 27%, 23%, 17%, 17%, and secondary patency rates were 63%, 60%,
      34%, 34%. CONCLUSION: Implantation of Dacron-covered stent-grafts for treatment
      of femoropopliteal lesions leads to high early and late restenosis rates, with a
      considerable rate of complications, such as fever and pain.

PMID- 11997537
TI  - Combined central retinal arterial and venous obstruction: emergency ophthalmic
      arterial fibrinolysis.
AB  - PURPOSE: To investigate the role of urokinase selectively perfused into the
      ophthalmic artery as an emergency treatment for combined central retinal arterial
      obstruction (CRAO) and central retinal venous obstruction (CRVO). MATERIALS AND
      METHODS: Over a 6-year period, 11 consecutive patients presented with recent
      combined CRAO and CRVO (< or =72 hours). Urokinase (300,000 IU) was selectively
      perfused via the femoral artery into the ophthalmic artery for 40 minutes.
      Evaluation criteria were Snellen visual acuity with best correction, funduscopic
      results, and retinal arteriovenous transit time assessed over a mean 3.5-year
      follow-up. Mean vision and retinal perfusion were tested by means of repeated
      measures analysis of variance. The correlation between visual improvement and
      retinal perfusion improvement was evaluated by means of Spearman rank
      correlation. RESULTS: Substantial improvement in vision and retinal perfusion was
      noted in seven of the 11 patients treated. Mean vision improvement was
      significant (P =.009) within 24-48 hours after fibrinolysis, increased until 1
      month after (P =.006), then remained stable throughout the follow-up (P >.10).
      Visual improvement correlated with retinal perfusion improvement during the
      period from before fibrinolysis to 24-48 hours after (P =.028). In all patients
      with improved results, retinal hemorrhages transiently increased. One patient had
      intravitreal hemorrhage shortly after fibrinolysis. CONCLUSION: For this uncommon
      clinical entity, which typically has a poor visual outcome, these results suggest
      that ophthalmic arterial fibrinolysis may restore retinal perfusion, which leads
      to rapid substantial visual improvement in many cases of combined CRAO and CRVO,
      without systemic complications, but it may be responsible for intravitreal
      hemorrhage.

PMID- 11997538
TI  - Which MR-derived perfusion parameters are the best predictors of infarct growth
      in hyperacute stroke? Comparative study between relative and quantitative
      measurements.
AB  - PURPOSE: To compare predictors of infarct growth in hyperacute stroke from a
      retrospective review of various relative and quantitative parameters calculated
      at perfusion-weighted magnetic resonance (MR) imaging performed within 6 hours
      after ictus. MATERIALS AND METHODS: Fluid-attenuated inversion recovery and
      diffusion- and perfusion-weighted images were obtained in 66 patients. The
      initial infarct was delineated on diffusion-weighted images; the hemodynamic
      disturbance, on apparent mean transit time (MTT) maps; and the final infarct, on
      follow-up fluid-attenuated inversion recovery images. Relative (without and with
      deconvolution) and quantitative values of the bolus arrival time, time to peak
      (TTP), apparent MTT or MTT, cerebral blood volume (CBV), peak height, and
      cerebral blood flow (CBF) index or CBF were calculated for initial infarct,
      infarct growth (final minus initial infarct contour), viable hemodynamic
      disturbance (apparent MTT minus final infarct contour), and contralateral mirror
      regions. Univariate and multivariate analyses (receiver operating characteristic
      curves and discriminant analysis) were performed to compare the diagnostic
      performance of these parameters for predicting infarct growth. RESULTS: At
      univariate analysis, relative peak height and quantitative CBF were the best
      predictors of infarct growth; at multivariate analysis, a function of peak height
      and TTP for relative measurements and CBF alone for quantitative measurements.
      Quantitative and relative measurements (without or with deconvolution) worked
      equally well. A combined relative peak height or TTP threshold (<54% or >5.2
      seconds, respectively) had a sensitivity of 71% and a specificity of 98%. A
      quantitative CBF threshold (<35 mL/min/100 g) had a sensitivity of 69% and a
      specificity of 85%. CONCLUSION: A combination of relative peak height and TTP
      measurements allowed the best prediction of infarct growth, which obviates more
      complex quantitative calculation.

PMID- 11997539
TI  - Proton MR spectroscopy of the cerebellum and pons in patients with degenerative
      ataxia.
AB  - PURPOSE: To investigate whether proton magnetic resonance (MR) spectroscopy is a
      useful complement to MR imaging in patients with degenerative ataxia. MATERIALS
      AND METHODS: Brain MR imaging and single-voxel proton MR spectroscopy of the
      right cerebellar hemisphere and pons were performed in 30 patients with sporadic
      (n = 16) or inherited (n = 14) degenerative ataxia and in 20 healthy control
      subjects. Several indexes of brainstem and cerebellar atrophy were measured on MR
      images, as well as the N-acetylaspartate/creatine (NAA/Cr), choline/Cr (Cho/Cr),
      and myo-inositol/Cr (mI/Cr) ratios in the MR spectra. Differences between
      patients and subjects were evaluated with the Kruskal-Wallis and Mann-Whitney
      tests, whereas correlation of clinical, MR imaging, and spectroscopic data was
      assessed with nonparametric Spearman rank correlation. RESULTS: Measurements of
      brainstem and cerebellar atrophy obtained from MR images revealed patients had
      olivopontocerebellar atrophy (OPCA) (n = 11), spinal atrophy (SA) (n = 8), or
      corticocerebellar atrophy (CCA) (n = 4). Seven patients did not fulfill the
      criteria for any group and were considered undefined. In patients with OPCA, the
      pontine and cerebellar NAA/Cr and Cho/Cr ratios were significantly decreased when
      compared with those of the control subjects. Pontine and cerebellar NAA/Cr ratios
      were also significantly reduced in patients with SA and CCA. Five patients with
      undefined ataxia had a substantial decrease of pontine or cerebellar NAA/Cr ratio
      when compared with that of the control subjects. In patients with OPCA, the
      pontine NAA/Cr ratio (but not the atrophy measurements) showed a correlation (P
      =.04) with disability. CONCLUSION: MR spectroscopy is a useful complement to MR
      imaging in patients with degenerative ataxia.

PMID- 11997540
TI  - Intramedullary spinal cord germinoma: case report and review of the literature.
AB  - A 33-year-old man with an intramedullary spinal cord germinoma was treated
      successfully with partial resection, combined chemotherapy with carboplatin and
      etoposide, and reduced-dose local-field radiation therapy. The authors believe
      this is the first case without syncytiotrophoblastic giant cells so treated. The
      literature is reviewed, and the appearance, radiologic and histopathologic
      features, and treatment of germinomas are discussed.

PMID- 11997541
TI  - "Ivy sign" in childhood moyamoya disease: depiction on FLAIR and contrast
      enhanced T1-weighted MR images.
AB  - PURPOSE: To compare contrast material-enhanced T1-weighted and fluid-attenuated
      inversion recovery (FLAIR) magnetic resonance (MR) images with or without
      gadolinium in depicting the leptomeningeal ivy sign in children with moyamoya
      disease. MATERIALS AND METHODS: Twenty-nine sets of FLAIR and postcontrast T1
      weighted MR images were available in 19 consecutive children with primary
      moyamoya disease confirmed with conventional and MR angiography. Contrast
      enhanced FLAIR MR images also were available in 15 sets. Two pediatric
      radiologists reviewed FLAIR and postcontrast T1-weighted images in separate
      sessions for the leptomeningeal ivy sign and assigned a rating of "present,"
      "absent," or "equivocal" by consensus. Unenhanced and contrast-enhanced FLAIR MR
      images were compared side by side to determine which better depicted
      leptomeningeal high signal intensities. RESULTS: Postcontrast T1-weighted MR
      images revealed the leptomeningeal ivy sign in 40 hemispheres (frequency of
      visualization, 71% [40 of 56 hemispheres]), whereas unenhanced FLAIR MR images
      depicted it in 26 hemispheres (frequency of visualization, 46% [26 of 56
      hemispheres]). An equivocal rating was given in 21 hemispheres versus in 11 on
      FLAIR and postcontrast T1-weighted images, respectively. FLAIR and postcontrast
      T1-weighted images agreed in 40 hemispheres. There was no case with a positive
      rating on FLAIR images when postcontrast T1-weighted images were negative.
      Unenhanced FLAIR MR imaging was superior to contrast-enhanced FLAIR imaging in
      seven hemispheres, whereas enhanced FLAIR was better in four of 28 hemispheres.
      In the remaining 17, findings with each sequence were similar. CONCLUSION:
      Contrast-enhanced T1-weighted images are better than FLAIR images for depicting
      the leptomeningeal ivy sign in moyamoya disease.

PMID- 11997543
TI  - Case 46: encephalomalacia in surviving twin after death of monochorionic co-twin.

PMID- 11997544
TI  - Accuracy of abnormal paraspinal muscle findings on contrast-enhanced MR images as
      indirect signs of unilateral cervical root-avulsion injury.
AB  - PURPOSE: To evaluate the accuracy of abnormal magnetic resonance (MR) findings in
      the paraspinal muscles as indirect signs of nerve-root avulsion injury. MATERIALS
      AND METHODS: Forty-three consecutive patients suspected of having unilateral root
      avulsion injury underwent MR imaging and were evaluated. Paraspinal muscles were
      evaluated for abnormal signal intensity on T1- and T2-weighted images, abnormal
      enhancement on images obtained after contrast material enhancement, and muscle
      volume loss. MR images were interpreted independently by two observers for
      interobserver variability. MR findings were compared with findings of root
      continuity, determined with a combination of surgery and clinical evaluation.
      Sensitivities, specificities, and kappa values of the findings were calculated.
      RESULTS: Sensitivities of MR findings in the paraspinal muscles indicating root
      avulsion injury were 88% (36 of 41 patients) for abnormal enhancement, 83% (34 of
      41 patients) for high signal intensity on T2-weighted images, 37% (15 of 41
      patients) for high signal intensity on T1-weighted images, and 71% (29 of 41
      patients) for muscle volume loss. Specificities for all findings were 100% (two
      of two patients). Of the paraspinal muscles, findings in the multifidus muscle
      were the most accurate and provided the highest interobserver agreement (kappa =
      0.81). CONCLUSION: Contrast material-enhanced abnormal MR findings in the
      paraspinal muscles are accurate in indicating root-avulsion injuries, and
      abnormal enhancement in the multifidus muscle is the most accurate among
      paraspinal muscle findings.

PMID- 11997545
TI  - Anterior cruciate ligament tears and associated meniscal lesions: assessment at
      dual-detector spiral CT arthrography.
AB  - PURPOSE: To assess dual-detector spiral computed tomographic (CT) arthrography of
      the knee in the evaluation of anterior cruciate ligament (ACL) tears and
      associated meniscal lesions. MATERIALS AND METHODS: ACL and meniscal
      abnormalities in 125 consecutive patients who underwent dual-detector spiral CT
      arthrography of the knee were evaluated on the basis of both initial
      interpretations and retrospective review of CT images and were compared with
      arthroscopic findings. The sensitivity and specificity of CT arthrography for the
      detection of ACL tears and meniscal lesions in knees with abnormal ACLs were
      determined. RESULTS: The sensitivities and specificities for the detection of ACL
      tears were 90% and 96%, respectively, at initial interpretation and 95% and 99%,
      respectively, at retrospective interpretation. The sensitivities and
      specificities for the detection of meniscal tears in knees with abnormal ACLs
      were 92% and 88%, respectively, at initial interpretation and 96% and 94%,
      respectively, at retrospective interpretation. CONCLUSION: Dual-detector spiral
      CT arthrography of the knee is an accurate method for detecting ACL tears and
      associated meniscal lesions.

PMID- 11997546
TI  - Differentiation of malignant and benign musculoskeletal tumors: combined color
      and power Doppler US and spectral wave analysis.
AB  - PURPOSE: To assess the use of combined color Doppler ultrasonography (US), power
      Doppler US, and spectral wave analysis (SWA) in differentiating malignant and
      benign musculoskeletal tumors. MATERIALS AND METHODS: Seventy-nine
      musculoskeletal tumors (34 malignant, 45 benign) were examined with color and
      power Doppler US and SWA. Two radiologists independently assessed US images and
      SWA findings. Echotexture and vessel characteristics such as stenoses,
      occlusions, loops, shunts, trifurcations, vascular pattern, and resistive index
      were evaluated. All tumors were subject to US-guided or open biopsy for
      histologic correlation. RESULTS: Combined color and power Doppler US and SWA
      revealed four major (stenosis, occlusion, trifurcation, vascular pattern) and
      three minor (shunt, self loop, resistive index) vessel characteristics, which
      proved helpful in differentiating benign from malignant lesions. Echotexture
      showed moderate sensitivity (82% [28 of 34 tumors]) and low specificity (38% [17
      of 45 tumors]). When comparing several combinations of vessel characteristics, a
      combination of any two major characteristics demonstrated the best results
      (sensitivity, 94% [33 of 39 tumors]; specificity, 93% [three of 45 tumors]).
      Combining more than two characteristics resulted in lower sensitivity.
      CONCLUSION: Combined color and power Doppler US and SWA may enable assessment of
      vascular architecture and altered flow of musculoskeletal tumors. Vascular
      architecture analysis enables differentiation of benign and malignant lesions and
      evaluation of musculoskeletal tumors.

PMID- 11997547
TI  - Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after
      gene transfer with a bicistronic adenovirus in mice.
AB  - PURPOSE: To compare two systems for assessing gene transfer to cancer cells and
      xenograft tumors with noninvasive gamma camera imaging. MATERIALS AND METHODS: A
      replication-incompetent adenovirus encoding the human type 2 somatostatin
      receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad
      hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro
      and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n
      = 23) were injected with 1 x 10(6) to 5 x 10(8) plaque-forming units (pfu) of Ad
      hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally
      bound, or trapped, technetium 99m ((99m)Tc)-labeled hSSTr2-binding peptide
      (P2045) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5
      iodouracil (FIAU), respectively. Iodine 125 ((125)I)-labeled FIAU was used in
      vitro and iodine 131 ((131)I)-labeled FIAU, in vivo. The (99m)Tc-labeled P2045
      and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different
      window settings with an Anger gamma camera. Treatment effects were tested with
      analysis of variance. RESULTS: Infected cells in culture trapped (125)I-labeled
      FIAU and (99m)Tc-labeled P2045; uptake correlated with the percentage of Ad
      hSSTr2-TK-positive cells. For 100% of infected cells, 24% +/- 0.4 (mean +/- SD)
      of the added (99m)Tc-labeled P2045 was trapped, which is significantly lower (P
      <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped. For the highest
      Ad-hSSTr2-TK tumor dose (5 x 10(8) pfu), the uptake of (99m)Tc-labeled P2045 was
      11.1% +/- 2.9 of injected dose per gram of tumor (thereafter, dose per gram),
      significantly higher (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/-
      0.4 dose per gram. (99m)Tc-labeled P2045 imaging consistently depicted hSSTr2
      gene transfer in tumors at all adenovirus doses. Tumor uptake of (99m)Tc-labeled
      P2045 positively correlated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor
      uptake did not correlate with vector dose. CONCLUSION: The hSSTr2 and TK proteins
      were simultaneously imaged following dual gene transfer with an adenovirus
      vector.

PMID- 11997548
TI  - Detection of low-contrast objects: experimental comparison of single- and multi
      detector row CT with a phantom.
AB  - PURPOSE: To compare single-detector row computed tomography (CT) and multi
      detector row CT by using an experimental phantom containing a contrast-detail
      modulus for detection of low-contrast structures to optimize acquisition
      protocols. MATERIALS AND METHODS: The parameters milliampere seconds,
      reconstructed section thickness, and elementary collimation for multi-detector CT
      were varied for two pitches with single- and multi-detector CT. For objective
      assessment of image quality, contrast-to-noise ratio (CNR) was calculated for an
      8-HU low-contrast 15-mm-diameter object. Subjective assessment of image quality
      was performed by means of visual detection of low-contrast objects of various
      sizes by four independent observers. For each acquisition protocol, the effective
      doses required to obtain the CNR thresholds allowing 100% detection of 5-, 7-,
      and 9-mm-diameter objects were compared at single- and multi-detector CT at
      comparable section sensitivity profile with analysis of variance. RESULTS:
      Significant correlation was found between CNR measurements and subjective object
      detection (r = 0.95, P <.05). CNRs of 1.0, 0.8, and 0.6 were required to detect
      100% of the 5-, 7-, and 9-mm-diameter objects, respectively. For reconstructed
      section thickness of 5-10 mm, comparable x-ray doses were required with single-
      and multi-detector CT to detect objects. For reconstructed sections thinner than
      5 mm, single- and multi-detector CT allowed detection of only the 7- and 9-mm
      thick objects, but a higher x-ray dose was required for multi- than for single
      detector CT (P <.05). CONCLUSION: Multi-detector CT is less effective than single
      detector CT in detection of small low-contrast objects if sections thinner than 5
      mm are used. Results for single- and multi-detector CT were similar for sections
      5 mm or thicker.

PMID- 11997549
TI  - Contrast-enhanced blood-pool MR angiography with optimized iron oxides: effect of
      size and dose on vascular contrast enhancement in rabbits.
AB  - PURPOSE: To investigate intravascular enhancement of bolus-injectable small and
      ultrasmall superparamagnetic iron oxides (USPIOs) of different particle sizes and
      relaxivities for first-pass and blood-pool magnetic resonance (MR) angiography.
      MATERIALS AND METHODS: Iron oxides with different particle sizes (hydrodynamic
      diameters, 21, 33, 46, and 65 nm) were bolus injected intravenously at three
      doses (10, 20, and 40 micromol per kilogram body weight). An extracellular
      contrast agent (gadopentetate dimeglumine) served as a control. MR angiography
      was performed multiple times after intravenous injection (5-120 minutes and 24
      hours later). Signal enhancement was calculated from signal intensity
      measurements in the abdominal aorta and renal and iliac arteries. RESULTS:
      Highest enhancement was seen during the first pass with all contrast agents.
      USPIO enhancement in the abdominal aorta increased significantly with decreasing
      particle size (65 nm vs 33 nm, 65 nm vs 21 nm; P <.01). CONCLUSION: The smallest
      iron oxide provided signal enhancement comparable with that of gadopentetate
      dimeglumine at 40 micromol iron per kilogram for first-pass investigations, with
      prolonged signal enhancement up to 25 minutes, allowing multiple measurements
      after injection of a single bolus.

PMID- 11997550
TI  - Influence of blood-pool contrast media on MR imaging and flow measurements in the
      presence of pulmonary arterial stents in swine.
AB  - PURPOSE: To compare the effects of various stents on magnetic resonance (MR)
      imaging flow volume measurements and to determine the value of a blood-pool MR
      imaging contrast medium in assessment of vascular stents. MATERIALS AND METHODS:
      In 11 pigs, six nitinol stents (Memotherm), four platinum stents (NuMed), and one
      elgiloy stent (Wallstent) were placed in the main pulmonary artery under x-ray
      fluoroscopic guidance. MR imaging was performed 3 months after stent placement
      before and after injection of NC100150 contrast medium. Blood flow volumes were
      assessed with velocity-encoded cine MR imaging through and next to the stent. The
      signal-to-noise ratio and width of susceptibility artifacts of the stents also
      were determined. Measurements were analyzed with the paired Student t test and
      Bland-Altman test, where appropriate. RESULTS: Blood flow volumes measured
      through the nitinol and platinum stents disclosed no significant difference
      between velocity-encoded cine MR imaging measurements through and next to the
      stent. On cine MR images, small susceptibility artifacts were observed around the
      nitinol and platinum stents. Signal-to-noise ratio in the stent lumen was reduced
      in nitinol and platinum stents when compared with that next to the stent. The
      elgiloy stent produced severe susceptibility artifacts, making measurement of
      flow volumes impossible. NC100150 injection caused no significant effect on flow
      volume measurements. It improved the signal-to-noise ratio of the pulmonary
      arterial lumen outside and, to a lesser extent, inside the stent. CONCLUSION:
      Assessment of morphology and flow volumes through nitinol and platinum stents is
      feasible with MR imaging. Blood-pool contrast media provide persistent signal
      enhancement in the pulmonary artery and, to a lesser extent, in the lumina of
      nitinol and platinum stents.

PMID- 11997551
TI  - Autoradiographic quantification of 18F-FDG uptake in experimental soft-tissue
      abscesses in rats.
AB  - PURPOSE: To use semiquantitative autoradiography to investigate
      fluorodeoxyglucose (FDG) uptake, distribution, and cellular localization in
      acute, early chronic, and late chronic soft-tissue infections. MATERIALS AND
      METHODS: Unilateral calf-muscle abscesses were induced in 12 Sprague-Dawley rats
      by means of intramuscular inoculation of 0.1 mL of bacterial suspension
      (Staphylococcus aureus, 1.2 x 10(9) CFU/mL). Following injection of 130-180 MBq
      of fluorine 18 FDG, autoradiography of the abscess and contralateral muscle was
      performed (10-microm section thickness) on days 2, 5, and 9 after infection.
      Detailed spatial correlation of autoradiographs and histopathologic samples was
      performed by means of image fusion. Regions of interest were placed in the
      abscess wall, and measured gray values were converted to kilobecquerels per cubic
      centimeter according to kilobecquerels of injected activity per gram of body
      weight, which yielded standardized uptake values (SUVs). RESULTS: Acute abscess
      formation was characterized by central necrosis predominantly surrounded by
      neutrophils and a second necrotic tissue layer that bordered neutrophil
      infiltrates peripherally. Areas with increased FDG uptake corresponded to
      cellular inflammatory infiltrates, mainly granulocytes. The corresponding SUV was
      calculated to be 4.08 +/- 0.65 (mean +/- SD). Early chronic phase showed mixed
      cellular infiltrate of granulocytes and macrophages that surrounded central
      necrosis with interspersed fibroblasts and only residual muscle necrosis layer
      within the abscess wall. FDG uptake was located where granulocytes and
      macrophages were present, as in acute infection (SUV = 5.32 +/- 2.30). Late
      chronic infection was characterized by a prominent layer of macrophages around
      residual central necrosis and fibroblast-enriched granulation tissue delineating
      the infection from muscle tissue. FDG uptake clearly coincided with the
      macrophages, and no substantial increase of FDG uptake was detected within
      fibroblast-enriched granulation tissue. The SUV was calculated as 7.97 +/- 0.21.
      Results of Kruskal-Wallis ANOVA demonstrated that the change in SUV with time was
      statistically significant (chi(2) = 7.42, P <.05). CONCLUSION: The highest FDG
      uptake coincides with areas of inflammatory cell infiltrates, predominantly in
      neutrophils in the acute phase and in macrophages in the chronic phase of soft
      tissue infection.

PMID- 11997552
TI  - T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET.
AB  - PURPOSE: To determine the sensitivity of fluorodeoxyglucose (FDG) positron
      emission tomography (PET) in patients with T1 (< or =3 cm) lung cancers.
      MATERIALS AND METHODS: One hundred eighty-five patients with 192
      histopathologically proved T1 lung cancers underwent FDG PET imaging at the time
      of diagnosis. PET results were correlated with tumor size, histopathologic
      findings, and patient outcome by using the two-sample t test, exact chi(2) test,
      and log rank test, respectively. RESULTS: Of the 192 lesions, 183 (95%) that
      ranged in size from 0.5 to 3.0 cm in diameter (mean, 2.0 cm) were positive at PET
      (ie, demonstrated increased FDG uptake). Of the 192 lesions, nine (5%) that
      ranged in size from 0.3 to 2.5 cm in diameter (mean, 1.3 cm) were negative at PET
      (ie, demonstrated low FDG uptake). Patients with small tumors, as well as those
      with carcinoid tumors and bronchioloalveolar cell carcinoma, were more likely to
      have a negative PET scan (P =.004, P =.003, respectively). In addition, patients
      with a negative PET scan who subsequently proved to have cancer had significantly
      longer survival than did patients with a positive scan and cancer (P =.043).
      CONCLUSION: Most T1 lung cancers show increased FDG uptake on PET scans.

PMID- 11997553
TI  - Risk of pulmonary embolism after a negative spiral CT angiogram in patients with
      pulmonary disease: 1-year clinical follow-up study.
AB  - PURPOSE: To evaluate the effect of pulmonary disease on diagnostic utility of
      spiral computed tomographic (CT) angiography in clinical practice. MATERIALS AND
      METHODS: Three hundred thirty-four patients, including 215 patients with
      pulmonary disease (group 1) and 119 patients with no history of respiratory
      disorder (group 2), were referred for thin-collimation CT angiography of the
      pulmonary circulation as the first-line diagnostic test. Patients with negative
      angiograms who had not received anticoagulation therapy and who could be
      clinically followed up at 3 months, 6 months, and 1 year were considered in the
      final study groups (n = 185); 135 patients had lung disease (group 3), and 50
      patients had no history of a respiratory disorder (group 4). RESULTS: Between
      groups 3 and 4, no significant differences were found in the referral location,
      age, and risk factors. Confident evaluation of pulmonary arteries down to the
      subsegmental level was performed in 31 (23%) patients in group 3 and in 15 (30%)
      in group 4 (P =.5). Three episodes of acute pulmonary embolism (PE), all fatal,
      were diagnosed in group 3 patients; two cases occurred 14 days and one case
      occurred 6 months after the negative spiral CT scan. The negative predictive
      value of spiral CT angiography was 98% (175 of 178) in the study group in which
      follow-up was performed, with no significant difference between the values in
      groups 3 (98% [132 of 135]) and 4 (100% [50 of 50]). CONCLUSION: Underlying
      respiratory disease does not affect the negative predictive value of thin
      collimation CT angiography, which appears to be a reliable tool in the work-up in
      this subgroup of patients with acute PE.

PMID- 11997554
TI  - Asymmetric ARDS following pulmonary resection: CT findings initial observations.
AB  - PURPOSE: To investigate whether asymmetric distribution of acute respiratory
      distress syndrome (ARDS) following lobectomy is due to compensatory
      hyperexpansion of the residual lung within the hemithorax operated on and to
      discern if this distribution reflects true asymmetry of the disease process.
      MATERIALS AND METHODS: Retrospective review of the intensive care unit database
      was performed over a period of 6 years to identify all cases of lung injury
      following lung surgery that satisfied the American-European consensus criteria
      for ARDS. Time to onset following surgery, time of subsequent computed
      tomographic (CT) examination, patient age and sex, and nature of surgery were
      recorded, as well as eventual patient status (ie, death or discharge).
      Availability of both preoperative and postoperative CT scans was required for
      inclusion for further analysis. These images were analyzed on a commercial CT
      workstation for the volume of lung resected and the pre- and postoperative volume
      and density of each lung. Expected postoperative densities (preoperative density
      adjusted for volume) were compared with observed postoperative densities.
      RESULTS: Review disclosed 583 patients who underwent lobectomy or segmentectomy.
      Seventeen patients (2.9%) developed postoperative ARDS. Nine of these patients
      had pre- and postoperative CT scans available for analysis. In eight of nine
      cases, density increased more in the nonoperated lung than in the operated lung
      (P =.01). The degree of density increase in the nonoperated lung was
      significantly greater (305 mg/mL; range, 48-449 mg/mL) than that in the operated
      lung (13 mg/mL; range, -198 to 231 mg/mL; P <.001). CONCLUSION: Following
      lobectomy, there appears to be a truly asymmetric form of ARDS rather than
      compensatory hyperexpansion of the residual lung on the operated side.

PMID- 11997555
TI  - Coronary artery calcium: absolute quantification in nonenhanced and contrast
      enhanced multi-detector row CT studies.
AB  - PURPOSE: (a) To determine the accuracy of multi-detector row computed tomography
      (CT) in the measurement of the calcium concentration in a cardiac CT calibration
      phantom and (b) to assess the correlation of a traditional 3-mm section width CT
      coronary screening protocol and a 1.25-mm section width CT angiography imaging
      protocol in the quantification of the absolute mass of coronary calcium in
      patients who underwent both coronary screening and CT angiography with a multi
      detector row CT scanner. MATERIALS AND METHODS: A heart phantom containing
      calcified cylinders was scanned to determine calibration factors and absolute
      calcium mass. In 50 patients, the variability (value 1 - value 2/mean value 1 -
      value 2), limit of agreement (+/-2SD value 1 - value 2), and systematic error
      (mean value 1 - value 2) of the total amount of coronary calcium calculated at
      traditional 3-mm section width CT and at 1.25-mm section width CT angiography
      were determined. RESULTS: The correlation coefficient between the 3-mm section
      width, nonenhanced protocol and the 1.25-mm section width CT angiography protocol
      was very high (r = 0.977) and the mean variability was low (19.7%) for the
      absolute mass. There was a systematic error of -6.7 mg and a limit of agreement
      between 45.0 mg and -58.5 mg. CONCLUSION: Use of the mass quantification
      algorithm in combination with a calibration phantom allows accurate
      quantification of coronary calcium. Measurements of calcium mass obtained at 1.25
      mm section width CT angiography have the best agreement with those obtained at
      the traditional 3-mm section width imaging protocol.

PMID- 11997556
TI  - The tattoo sign.

PMID- 11997557
TI  - Interpretation of digital mammograms: comparison of speed and accuracy of soft
      copy versus printed-film display.
AB  - PURPOSE: To compare the speed and accuracy of the interpretations of digital
      mammograms by radiologists by using printed-film versus soft-copy display.
      MATERIALS AND METHODS: After being trained in interpretation of digital
      mammograms, eight radiologists interpreted 63 digital mammograms, all with old
      studies for comparison. All studies were interpreted by all readers in soft-copy
      and printed-film display, with interpretations of images in the same cases at
      least 1 month apart. Mammograms were interpreted in cases that included six
      biopsy-proved cancers and 20 biopsy-proved benign lesions, 20 cases of probably
      benign findings in patients who underwent 6-month follow-up, and 17 cases without
      apparent findings. Area under the receiver operating characteristic curve (A(z)),
      sensitivity, and specificity were calculated for soft-copy and printed-film
      display. RESULTS: There was no significant difference in the speed of
      interpretation, but interpretations with soft-copy display were slightly faster.
      The differences in A(z), sensitivity, and specificity were not significantly
      different; A(z) and sensitivity were slightly better for interpretations with
      printed film, and specificity was slightly better for interpretations with soft
      copy. CONCLUSION: Interpretation with soft-copy display is likely to be useful
      with digital mammography and is unlikely to significantly change accuracy or
      speed.

PMID- 11997558
TI  - Differences between computer-aided diagnosis of breast masses and that of
      calcifications.
AB  - PURPOSE: To compare the performance of a computer-aided diagnosis (CAD) system
      for diagnosis of previously detected lesions, based on radiologist-extracted
      findings on masses and calcifications. MATERIALS AND METHODS: A feed-forward,
      back-propagation artificial neural network (BP-ANN) was trained in a round-robin
      (leave-one-out) manner to predict biopsy outcome from mammographic findings
      (according to the Breast Imaging Reporting and Data System) and patient age. The
      BP-ANN was trained by using a large (>1,000 cases) heterogeneous data set
      containing masses and microcalcifications. The performances of the BP-ANN on
      masses and microcalcifications were compared with use of receiver operating
      characteristic analysis and a z test for uncorrelated samples. RESULTS: The BP
      ANN performed significantly better on masses than microcalcifications in terms of
      both the area under the receiver operating characteristic curve and the partial
      receiver operating characteristic area index. A similar difference in performance
      was observed with a second model (linear discriminant analysis) and also with a
      second data set from a similar institution. CONCLUSION: Masses and calcifications
      should be considered separately when evaluating CAD systems for breast cancer
      diagnosis.

PMID- 11997559
TI  - Peritoneal metastases: detection with spiral CT in patients with ovarian cancer.
AB  - PURPOSE: To determine the accuracy of spiral computed tomography (CT) in the
      depiction of peritoneal metastases by using surgical findings in patients with
      ovarian cancer as the standard of reference. MATERIALS AND METHODS: Three
      independent readers reviewed the preoperative CT scans obtained in 64 patients
      who underwent primary surgery for ovarian cancer. Readers rated the likelihood of
      peritoneal metastases on a five-point scale and recorded the presence or absence
      of ascites, parietal peritoneal thickening or enhancement, and small-bowel wall
      thickening or distortion. Peritoneal metastases were identified as nodular,
      plaquelike, or infiltrative soft-tissue lesions in the peritoneal fat or on the
      peritoneal surface. Area under the receiver operating characteristic curve was
      calculated for each reader. Interreader agreement was evaluated with the kappa
      statistic. Descriptive statistical data were determined with dichotomized ratings
      (1-3 = absent; 4-5 = present). RESULTS: Areas under the receiver operating
      characteristic curves for the three readers were 0.95, 0.93, and 0.89. Paired
      kappa values ranged from 0.75 to 0.91. Reader sensitivity for metastases 1 cm or
      smaller in maximum diameter (25%-50%) was significantly (P <.05) lower than
      overall sensitivity (85%-93%). Ascites, parietal peritoneal thickening or
      enhancement, and small-bowel wall thickening or distortion demonstrated positive
      predictive values of 72%-93%, with kappa values of 0.12-0.80. CONCLUSION: Spiral
      CT is accurate in the depiction of peritoneal metastases from ovarian cancer,
      although sensitivity is reduced in patients with tumor implants 1 cm or smaller.
      Ancillary signs of peritoneal malignancy are limited by low interobserver
      agreement.

PMID- 11997560
TI  - Dynamic MR imaging of the pelvic floor performed with patient sitting in an open
      magnet unit versus with patient supine in a closed-magnet unit.
AB  - PURPOSE: To compare open-magnet magnetic resonance (MR) imaging performed with
      the patient sitting with dynamic closed-magnet MR imaging of the pelvic floor
      performed with the patient supine. MATERIALS AND METHODS: Thirty-eight patients
      underwent dynamic 1.5-T closed-magnet pelvic floor MR imaging while in the supine
      position. Midsagittal T2-weighted single-shot fast spin-echo and T1-weighted
      multiphase spoiled gradient-recalled-echo (SPGR) MR images were obtained before
      and after rectal contrast agent administration, respectively, with the patient at
      rest, straining, and maximally contracting the sphincter. Subsequently, the
      patient was transferred to an open 0.5-T system. Midsagittal multiphase T1
      weighted SPGR MR images were then obtained every 2 seconds with the patient
      sitting while at rest, maximally contracting the sphincter, straining, and
      defecating. Images were analyzed with regard to presence of enteroceles, anterior
      rectoceles, intussusceptions, rectal descents, bladder descents, and vaginal
      vault descents. RESULTS: All intussusceptions were missed at supine MR imaging.
      With sitting MR imaging as the reference standard, the sensitivity of supine MR
      imaging was 79% for depiction of bladder descents. When MR findings were graded
      and clinically irrelevant MR findings were excluded, sensitivity increased to
      100% for depiction of bladder descents and anterior rectoceles and to 96% for
      depiction of rectal descents. CONCLUSION: Dynamic supine MR imaging performed
      with a closed-configuration unit before and after rectal contrast agent
      administration appears to be an alternative to sitting MR defecography performed
      with an open-configuration unit for diagnosis of clinically relevant pelvic floor
      abnormalities.

PMID- 11997561
TI  - 3D MR angiography of renal arteries: comparison of volume rendering and maximum
      intensity projection algorithms.
AB  - PURPOSE: To compare volume rendering (VR) and maximum intensity projection (MIP)
      as postprocessing techniques of magnetic resonance (MR) angiography for detection
      and quantification of renal artery stenosis. MATERIALS AND METHODS: Twenty-seven
      patients underwent three-dimensional contrast material-enhanced MR angiography of
      the renal arteries with a 1.5-T imager. For each renal artery, targeted MIP and
      VR images were reconstructed in oblique coronal and transverse orientations. For
      each modality, image generation and evaluation were performed interactively by
      two independent radiologists blinded to angiographic results. In comparison with
      digital subtraction angiography (DSA) findings, stenosis quantification and
      detection by using MIP and VR were evaluated with the use of 50% and 70% cutoff
      points by using linear regression analysis and 2 x 2 tables. Overall image
      quality and vascular delineation on MIP and VR images were also compared.
      RESULTS: All main and accessory renal arteries depicted at DSA were also
      demonstrated on MIP and VR images. VR performed slightly better than MIP for
      quantification of stenoses greater than 50% (VR: r(2) = 0.84, P <.001; MIP: r(2)
      = 0.38, P =.001) and significantly better for severe stenoses (VR: r(2) = 0.83, P
      <.001; MIP: r(2) = 0.21, P =.1). For detection of stenosis, VR yielded a
      substantial improvement in positive predictive value (VR: 95% and 90%; MIP: 86%
      and 68% for stenoses greater than 50% and 70%, respectively). Image quality
      obtained with VR was not significantly better than that with MIP; however,
      vascular delineation on VR images was significantly better. CONCLUSION: The VR
      technique of renal MR angiography enabled more accurate detection and
      quantification of renal artery stenosis than did MIP, with significantly improved
      vascular delineation.

PMID- 11997562
TI  - Characterization of liver lesions with mangafodipir trisodium-enhanced MR
      imaging: multicenter study comparing MR and dual-phase spiral CT.
AB  - PURPOSE: To evaluate whether mangafodipir trisodium (Mn-DPDP)-enhanced magnetic
      resonance (MR) imaging surpasses dual-phase spiral computed tomography (CT) in
      differentiating focal liver lesions. MATERIALS AND METHODS: One hundred forty
      five patients who had or were suspected of having focal liver lesions were
      included in a multicenter study and underwent dual-phase spiral CT and enhanced
      MR imaging. Image interpretations performed by independent experienced
      radiologists were compared with the final diagnosis that was based on all
      available clinical information (including histopathologic findings in 77
      patients) and that was determined with consensus. Differences in classifications
      by using either enhanced MR imaging or dual-phase spiral CT were analyzed with
      the McNemar test, and receiver operating characteristic (ROC) curves were used to
      compare the diagnostic performance of enhanced MR imaging and dual-phase spiral
      CT. RESULTS: Lesion classification was correct in 108 (74%) patients with
      enhanced MR imaging and in 83 (57%) with dual-phase spiral CT (P =.001). Lesions
      were correctly classified as either malignant or benign in 123 (85%) patients
      with enhanced MR imaging and in 98 (68%) with dual-phase spiral CT (P =.001).
      Classification of lesions as either hepatocellular or nonhepatocellular was
      correct in 130 (90%) patients with enhanced MR imaging and in 93 (64%) with dual
      phase spiral CT (P =.001). These differences remained when analyses were
      restricted to histopathologically confirmed diagnoses. Comparison of the ROC
      curves illustrated that enhanced MR imaging performance surpassed that of dual
      phase spiral CT. CONCLUSION: Mn-DPDP-enhanced MR imaging is superior to dual
      phase spiral CT in classification of focal liver lesions.

PMID- 11997563
TI  - Liver lesions: manganese-enhanced MR and dual-phase helical CT for preoperative
      detection and characterization comparison with receiver operating characteristic
      analysis.
AB  - PURPOSE: The purpose of this study was to compare, by means of receiver operating
      characteristic (ROC) analysis, dual-phase helical computed tomography (CT) and
      manganese-enhanced magnetic resonance (MR) imaging in the detection and
      characterization of hepatic lesions in patients prior to surgery. MATERIALS AND
      METHODS: Twenty-five patients known to have or suspected of having hepatic
      lesions who were eligible for surgery underwent dual-phase (ie, arterial and
      portal phase) helical CT and phased-array MR imaging (ie, unenhanced fast spin
      echo T2-weighted imaging and gradient-echo T1-weighted imaging performed before
      and after administration of mangafodipir trisodium). All images were reviewed
      independently by three off-site blinded reviewers who separately reviewed the CT
      scans and MR images. The standard of reference was findings at surgery,
      intraoperative ultrasonography (US), and histopathologic examination. ROC curves
      were established to analyze the results for each reader and modality. RESULTS:
      Ninety-four lesions (77 malignant and 17 benign) were revealed at surgery,
      intraoperative US, and/or histopathologic examination. The overall rate of lesion
      detection for the three readers at CT was 81.9% +/- 7.8, 90.4% +/- 5.9, and 76.6%
      +/- 8.6. At MR imaging, the detection rates were 72.3% +/- 9.0, 71.3% +/- 9.1,
      and 69.1% +/- 9.3 (P =.001 for the difference between MR and CT). The average
      rate of false-positive diagnoses in patients was 14.1% at CT and 6.4% at MR
      imaging (P =.06 for the difference between MR and CT). The mean areas under the
      alternative-free-response ROC curves were 0.74 for MR and 0.72 for CT (P =.751,
      not significant). CONCLUSION: In detection and characterization of liver lesions,
      manganese-enhanced MR imaging and dual-phase helical CT were not statistically
      different.

PMID- 11997564
TI  - Radiologists' performance in the diagnosis of liver tumors with central scars by
      using specific CT criteria.
AB  - PURPOSE: To determine the performance of radiologists with differing levels of
      expertise in the diagnosis of the most common types of liver tumors with central
      scars (ie, focal nodular hyperplasia [FNH], fibrolamellar hepatocellular
      carcinoma [HCC], and large hepatic hemangioma) by using specific computed
      tomographic (CT) findings. MATERIALS AND METHODS: Review of medical records at
      the University of Pittsburgh Medical Center identified patients with a total of
      64 liver tumors that had central scars-including 29 cases of FNH, 20
      fibrolamellar HCCs, and 15 large (>3.5 cm in diameter) hemangiomas-and with CT
      scans available for review. Retrospective review of these scans was performed
      individually by six radiologists who were blinded to the diagnosis, including two
      faculty abdominal radiologists, one abdominal imaging fellow, and three radiology
      residents. Individual performance was evaluated by means of receiver operating
      characteristic analysis, and interobserver agreement was measured by using the
      Cronbach alpha. Individual CT findings that may allow differentiation of tumor
      types were identified with the Kruskal-Wallis test. RESULTS: CT allowed good to
      excellent interobserver agreement in the diagnosis of tumor type and in
      recognition of differential findings among the three types. The individual
      accuracy of diagnosis was very good, with the average area under the receiver
      operating characteristic curve ranging from 0.81 to 0.90. Although the faculty
      radiologists performed the best, the differences in performance between the
      subgroups of readers and the levels of confidence in diagnosis were not
      statistically significant. The diagnosis of fibrolamellar HCC was the most
      accurate and had the highest sensitivity, followed by FNH and large hemangioma.
      Clinical and CT findings that were found to be statistically significant in
      differentiating tumor types were patient age and sex, tumor size larger than 10
      cm, width of tumor scars, invasion of vessels, nodular centripetal enhancement,
      marked hyperattenuation on arterial phase images, lymphadenopathy, heterogeneity,
      extrahepatic metastases, surface lobulation, calcification, and isoattenuation
      with liver tissue on portal venous phase images. CONCLUSION: CT allows accurate
      differentiation of the most common types of liver tumors with central scars,
      including FNH, fibrolamellar HCC, and large hemangioma.

PMID- 11997565
TI  - Mucinous versus nonmucinous gastric carcinoma: differentiation with helical CT.
AB  - PURPOSE: To assess the capability of helical computed tomography (CT) to assist
      in the differentiation between mucinous and nonmucinous gastric carcinomas, with
      a focus on the thickened stomach wall itself. MATERIALS AND METHODS: In 62
      patients with pathologically proved mucinous (n = 21) or nonmucinous (n = 41)
      gastric carcinomas, contrast material-enhanced helical CT images were obtained.
      The gross appearance, contrast enhancement pattern, predominant thickened layer,
      and degree of enhancement were retrospectively evaluated. Statistical analyses
      were performed with Fisher exact, chi(2), and Student t tests. A P value of less
      than.05 was considered to indicate a statistically significant difference.
      RESULTS: The most common type of gross appearance in both carcinomas was
      fungating: It occurred in 71% of patients with mucinous carcinomas and in 59% of
      patients with nonmucinous carcinomas. The next most common gross appearance type
      was ulcerative (24% of patients) in nonmucinous carcinomas and diffusely
      infiltrative (29% of patients) in mucinous carcinomas (P =.009). The most common
      contrast enhancement pattern was homogeneous (61% of patients) in nonmucinous
      carcinomas and layered (62% of patients) in mucinous carcinomas (P =.001). These
      findings were significantly different. The predominantly affected thickened layer
      was the high-attenuating inner layer or the entire layer (88% of patients) in
      nonmucinous carcinomas and the low-attenuating middle or outer layer (57% of
      patients) in mucinous carcinomas. Only two mucinous tumors showed miliary
      punctate calcifications in infiltrative lesions. CONCLUSION: Helical CT may
      assist in distinguishing mucinous from nonmucinous gastric carcinoma, primarily
      on the basis of enhancement pattern, predominant layer of the thickened wall,
      gross appearance, and presence of calcifications.

PMID- 11997566
TI  - Pancreatic cysts: depiction on single-shot fast spin-echo MR images.
AB  - PURPOSE: To evaluate single-shot fast spin-echo (SE) magnetic resonance (MR)
      imaging for depiction of pancreatic cysts in a large number of patients and to
      analyze cyst prevalence with respect to patient age and sex and other clinical
      information. MATERIALS AND METHODS: Single-shot fast SE images of the pancreas
      were obtained in 1,444 patients. The images were reviewed for presence of
      pancreatic cysts, which were classified as simple and nonsimple types, and cyst
      diameters were measured. kappa statistic, Fisher exact, McNemar Q, and Pearson
      product moment correlation tests were performed. RESULTS: Two hundred eighty
      three (19.6%) patients had at least one pancreatic cyst. The prevalence of
      pancreatic cysts increased with age (r = 0.96). The percentages of male and
      female patients with pancreatic cysts (20.4% vs 18.8%) were not significantly
      different. Two hundred seventy-one (18.8%) patients had simple cysts, and 147
      (10.2%) had nonsimple cysts. Of 283 patients with pancreatic cysts, 158 (55.8%)
      had only one pancreatic cyst. The number of patients with multiple cysts
      increased with age after 70 years. Four hundred fifteen (83.8%) cysts were 10 mm
      in diameter or smaller; 56 (11.3%), 11-20 mm in diameter; and 24 (4.9%), 21 mm in
      diameter or larger. Sixteen (5.7%) patients with pancreatic cysts had malignant
      pancreatic tumors, and 75 (26.5%) patients had pancreatitis. CONCLUSION: The
      prevalence of pancreatic cysts at single-shot fast SE MR imaging-especially cysts
      with a diameter smaller than 10 mm-is similar to that of pancreatic cysts at
      autopsy and higher than that of pancreatic cysts at transabdominal
      ultrasonography. Prevalence is especially high in patients with pancreatitis.

PMID- 11997567
TI  - Measurement of breast density with dual X-ray absorptiometry: feasibility.
AB  - Dual x-ray absorptiometry (DXA) was used to quantify breast density with a
      phantom and with cadaveric breasts. With DXA, percentage of fat correlated with
      percentage of glandular density of the phantom (r > 0.998) and with density at
      mammography (r(adjusted) = 0.83). DXA precision (SD) was 0.5% without and 1.1%
      with breast repositioning. DXA devices can be used to accurately and precisely
      estimate breast tissue density.

PMID- 11997568
TI  - Breast cancer: regional blood flow and blood volume measured with magnetic
      susceptibility-based MR imaging--initial results.
AB  - The purpose of this study was to quantify microcirculation in breast neoplasms
      with magnetic susceptibility-based contrast material-enhanced magnetic resonance
      imaging. With this imaging method for invasive cancers, the mean values of the
      ratios of tumor to normal blood flow and blood volume were significantly higher
      (P <.002) than those for benign or normal tissue. The method allows independent
      measurement of regional blood flow and blood volume in breast cancers.

PMID- 11997569
TI  - Carotid artery atherosclerosis: in vivo morphologic characterization with
      gadolinium-enhanced double-oblique MR imaging initial results.
AB  - In nine subjects with carotid atherosclerosis, double-oblique, contrast material
      enhanced, double inversion-recovery, fast spin-echo magnetic resonance (MR)
      images were acquired through atheroma in the proximal internal carotid artery.
      Fibrocellular tissue within atheroma selectively enhanced 29% after
      administration of gadolinium-based contrast agent. Contrast enhancement helped
      discriminate fibrous cap from lipid core with a contrast-to-noise ratio as good
      as or better than that with T2-weighted MR images but with approximately twice
      the signal-to-noise ratio (postcontrast images, 36.6 +/- 3.6; T2-weighted images,
      17.5 +/- 2.1; P <.001).

PMID- 11997570
TI  - MR guidance of sympathetic nerve blockade: measurement of vasomotor response
      initial experience in seven patients.
AB  - The authors performed sympathetic nerve blockades in seven patients with
      peripheral ischemia and possible autonomic dysfunction. Magnetic resonance (MR)
      imaging was used to guide needle placement, to monitor distribution of injected
      agents, and to measure increases in blood flow, which were as much as 10-fold. MR
      imaging can provide both procedural imaging guidance and measurement of efficacy
      for sympathetic nerve blocks.

PMID- 11997571
TI  - Breast cancer may not be seen sonographically either.

PMID- 11997572
TI  - Palpable breast abnormalities must be resolved histologically.

PMID- 11997573
TI  - Testicular microlithiasis.

PMID- 11997574
TI  - MR spectroscopy in the human fetus.

PMID- 11997575
TI  - What is the importance of flow void artifact increase at MR imaging with gradient
      recalled-echo sequences?

PMID- 11997576
TI  - Validation of the effectiveness and efficiency of newer techniques.

PMID- 11997577
TI  - Variations in breast MR imaging protocol.

PMID- 11997578
TI  - Harold Gordon Jacobson, MD.

PMID- 11997580
TI  - Death receptor signaling giving life to ectodermal organs.
AB  - A new tumor necrosis factor (TNF) pathway has been identified that has an
      important function in the regulation of embryonic development. Three key
      components of this pathway are previously unknown proteins: the TNF ligand
      ectodysplasin (also known as EDA), its death domain-containing receptor EDAR, and
      the death domain adapter molecule EDARADD. This pathway was discovered and
      delineated through the cloning of genes that cause human hypohidrotic ectodermal
      dysplasia (HED) syndromes and by analysis of the corresponding mouse mutants
      (Tabby, downless, and crinkled) showing defects in hair, teeth, and several
      exocrine glands. EDAR signaling is mediated by the activation of nuclear factor
      kappa B, but other downstream targets are not known. Ectodysplasin-EDAR signaling
      mediates cell interactions within the ectoderm and regulates the initiation and
      morphogenesis of hair and teeth. It is also necessary for the development of fish
      scales, indicating that this pathway and its function have been conserved during
      the evolution of ectodermal organs.

PMID- 11997581
TI  - Sticky caveats in an otherwise glowing report: oligomerizing fluorescent proteins
      and their use in cell biology.
AB  - Fluorescent proteins from sea creatures have revolutionized the study of cell
      biology and signal transduction in many ways. Zacharias discusses some of the
      technical caveats to working with these proteins when they are fused to cellular
      proteins to track protein localization and interactions. Special attention is
      paid to problems arising from oligomerization of these fluorescent proteins and
      how that impacts protein interactions detected by fluorescence resonance energy
      transfer (FRET).

PMID- 11997582
TI  - A confirmatory study of Rasch-based optimal categorization of a rating scale.
AB  - The purpose of this study was to determine if the characteristics of the optimal
      categorization identified by the Rasch analysis in a previous study can be
      maintained when the revised scale is applied to the same population. Based on the
      results of the previous Rasch analysis, a 23-item exercise barrier scale was
      modified from its original five-category structure ("Very often" = 1, "Often" =
      2, "Sometimes" = 3, "Rarely" = 4, and "Never" = 5) to a three-category structure
      ("Very Often" = 1, "Sometimes" = 2, and "Never" = 3). The modified scale was then
      mailed to the original sample (N = 381), of which 206 returned the survey; a
      return rate 57.5%. The data was again analyzed using the Rasch Rating Scale
      model. Overall, the Rasch model fit data well and similar change patterns were
      observed in two category statistics provided by the Rasch analysis. The order of
      item severity was also well kept and the correlation of item severities generated
      from two studies was very high, with r = .98. In addition, similar results were
      also found in respondents' ability estimations, and the correlation between the
      two studies was moderately high, with r = .68. These results verified that the
      characteristics of the optimal categorization identified by the Rasch post-hoc
      analysis can be maintained after the original scale was modified based on such an
      analysis.

PMID- 11997583
TI  - Dimensionality and construct validity of School Development Expectation Scale for
      secondary students.
AB  - This study aims to establish the dimensionality and construct validity of the
      School Development Expectation Scale for use with Year 12 students. The scale is
      made up of five expectation subscales in the vocational, academic, personal,
      social and religious development domains. The validation sample comprised 8,310
      Year 12 students from 70 schools. Traditional confirmatory factor analysis
      supported the theory postulated five-factor model. The scale was then calibrated
      using Rasch rating scale model. Recommendations were made regarding how to
      further refine the scale.

PMID- 11997584
TI  - Item grouping effects on invariance of attitude items.
AB  - The purpose of this study was to evaluate the effects of item grouping on local
      independence and item invariance, the characteristics of items scaled under the
      Rasch model that make them sample-free. Item fit and calibration for attitude
      items presented in a grouped versus random order were examined. It was
      hypothesized that grouping items to facilitate interpretation central to a
      construct may result in a failure of invariance. Data were 107 responses to a 40
      item mail survey of teachers' opinions about the Ontario Ministry's grade 9
      literacy test. Effects of grouping and item phrasing on invariance were found.
      Results, however, generally support the use of grouping of items to provide a
      higher person separation, and potentially higher quality data.

PMID- 11997585
TI  - Level of Activity in Profound/Severe Mental Retardation (LAPMER): a Rasch-derived
      scale of disability.
AB  - Classification of Mental Retardation (MR) into severe and profound is based on IQ
      threshold (<35 and 20% respectively) and on quite generic descriptions of
      deficits in adaptive behavior. The LAPMER scale (after Level of Activity in
      Profound/severe Mental Retardation) was developed as a measure of severity
      through observed behavior in adult patients. The Rasch analysis (RA, in its
      rating scale model) was adopted as a guide for selection of items,
      conceptualization of item levels, and validation of the overall instrument. The
      RA provides estimates on a continuum measure corresponding to the discrete
      cumulative score. A model prescribes the expected scores on each subject-item
      interaction. Discrepancies between observed and expected scores allow diagnostic
      procedures on coherence (fit) of both subjects and items. The final version
      included 8 items: Feeding, Sphincters, Communication, Manipulation, Dressing,
      Locomotion, Spatial Orientation and Praxiae, scored 0/1 or 0/1/2 (cumulative
      range for the total set of items was 0-13) the higher the score, the better the
      performance. The test can be administered in 15 minutes through observation or
      inquiry from proxies and personnel. A psychologist rated 146 permanent hosts of a
      large Institute for mentally retarded adults (51 profound and 95 severe, 91 male,
      age 18-63, median 36). Median score was 6/13, IQR 1-9, range 0-12, 19% of cases
      scored 0. Cronbach a for internal consistency was 0.90. Fifty-seven patients were
      also independently scored by another psychologist. Between-rater Cohen's k
      reliability index ranged from 0.77-0.96 across items. Median raw scores were 1
      and 8 in profound and severe cases, respectively (p<0.001). Rasch person
      reliability coefficient, a 0 to 1 index of internal consistency analogous to
      Crohnbach a, was 0.92. For each item the standardized differences between
      observed and model-expected scores (residuals) were c2 tested (a level 0.05)
      across sub-groups of patients. These were: profound vs. severe cases, and classes
      of motor impairment (tetra-,hemi-,para-plegic and unimpaired), matched for
      overall ability measure. For 6 items some residuals were found to be
      statistically significant. Absolute differences ranged from 0 to 0.7 raw score
      points, with no systematic patterns. Gender, age group and rater did not bias the
      measure. Residuals did not correlate meaningfully across pairs of items
      (r<(0.5)), further supporting the unidimensionality of the measure. The scale
      seems a valid tool for classification of adult severe and profound MR cases.

PMID- 11997586
TI  - Optimizing rating scale category effectiveness.
AB  - Rating scales are employed as a means of extracting more information out of an
      item than would be obtained from a mere "yes/no", "right/wrong" or other
      dichotomy. But does this additional information increase measurement accuracy and
      precision? Eight guidelines are suggested to aid the analyst in optimizing the
      manner in which rating scales categories cooperate in order to improve the
      utility of the resultant measures. Though these guidelines are presented within
      the context of Rasch analysis, they reflect aspects of rating scale functioning
      which impact all methods of analysis. The guidelines feature rating-scale-based
      data such as category frequency, ordering, rating-to-measure inferential
      coherence, and the quality of the scale from measurement and statistical
      perspectives. The manner in which the guidelines prompt recategorization or
      reconceptualization of the rating scale is indicated. Utilization of the
      guidelines is illustrated through their application to two published data sets.

PMID- 11997587
TI  - [Direct action and indirect effects of gravity].

PMID- 11997588
TI  - [Scientific aims of the International Space Station Centrifuge Facility].

PMID- 11997589
TI  - [On the development status of the International Space Station Centrifuge
      Facility].

PMID- 11997590
TI  - [Artificial gravity and space plant science].

PMID- 11997591
TI  - [Usefulness of the Centrifuge Accommodation Module for analyzing gravity
      responses in plant seedlings].
AB  - Onboard centrifuges are indispensable tools for clarifying the effects of
      microgravity on various physiological processes in plant seedlings. Centrifuges
      are basically attached to the incubators designed for the International Space
      Station (ISS). However, because of the limitation in size, that loaded to the
      Cell Biology Experiment Facility (CBEF) is usable only to some small seedlings
      such as Arabidopsis. The Centrifuge Accommodation Module (CAM) has great
      advantages in the size and the amounts of plant materials feasible to load, the
      quality of acceleration produced, and the easiness of operation on it. The CAM is
      an apparatus that characterizes the ISS most and its construction on schedule is
      highly expected.

PMID- 11997592
TI  - [On-board centrifuge required for space experiments of plants].

PMID- 11997593
TI  - [Aquatic animals and use of centrifuge in space experiments].
AB  - There are some experiments which do not need a centrifuge apparatus in space,
      however, for other space experiments the use of centrifuge is indispensable as
      the control. The characteristics of these two types of space experiments are
      explained. Generally, the more quantitatively the phenomenon is analyzed, the
      greater the need of centrifuge apparatus becomes. The centrifuge in space can
      realize various gravity values ranging from 0 to 1 G, and this will extend the
      present biology to a more universal biology.

PMID- 11997594
TI  - [Using centrifuge for gravitational biology in mammals].

PMID- 11997595
TI  - [Usefulness of the centrifuge in the International Space Station: from the
      viewpoint of our space experiment in the rat].

PMID- 11997596
TI  - [Proposal from space radiation biologists. Importance of Centrifuge Facility in
      the study of biological effect by space radiation].
AB  - In microgravity, astronauts were constantly exposed to space radiation containing
      various kinds of radiation with a low-dose rate during long-term stays in space.
      It is very difficult to define the relative biological effectiveness (RBE) of
      space radiation under microgravity. In order to understand correct the RBE of
      space radiation, therefore, utilization of Centrifuge Facility is desired as a
      control experiment at orbit for removing other factors such as microgravity
      except space radiation. Here, we summarized the importance of Centrifuge Facility
      in the study of biological effect of space radiation.

PMID- 11997597
TI  - [Gravitational biology of integrative organisms and ecological system--the road
      map of space activities].
AB  - History of the International Space Station, ISS, and planning of its scientific
      use are described in this essay. Fundamental gravitational biology and its
      facility on the ISS have been identified to have the highest priority to conduct
      scientific experiments with variable G environment in orbit. The road map of
      space activities is clearly directing the efforts toward manned Mars exploration.
      The Centrifuge is a core element of the facilities dedicated to this endeavor.
      Several research subjects are discussed with the results obtained from the past
      space experiments. Direct effects of gravity on the biological system at the
      level of integrative organisms are major subjects of study that will be conducted
      on the large scaled centrifuge.

PMID- 11997598
TI  - [The study of the biological effects of space radiation and microgravity].

PMID- 11997599
TI  - [Study of growth regulation mechanisms in plants by a space experiment].

PMID- 11997600
TI  - [Microgravity modulates function of osteoblast].

PMID- 11997601
TI  - [Effects of space flight on the afferent nerve of the aortic baroreflex in the
      mature rat].

PMID- 11997602
TI  - [Adaptation of human beings to the gravity-changing stress--examination by serum
      and peripheral lymphocyte samples].

PMID- 11997603
TI  - [Dynamic instability of biological system under natural and experimental gravity
      condition].

PMID- 11997604
TI  - [Gravitational environment and ciliary and flagellar movement].

PMID- 11997605
TI  - [Microtubule dynamics in relation to growth response to gravity in plant cells].

PMID- 11997606
TI  - [Effects of gravity-vector changing for endothelial (correction of endotherial)
      cells].

PMID- 11997607
TI  - [Tubulin/microtubule dynamics and alpha B-crystallin].

PMID- 11997608
TI  - ["Space Eye Net" education system using Kibo].

PMID- 11997609
TI  - [Elementary science education based on space and life].

PMID- 11997610
TI  - [The view on the education of space science from Young Astronauts Club (YAC)].

PMID- 11997611
TI  - [Results and analysis for "Survey and Questionnaire of the Universe" by junior
      and senior high school students].

PMID- 11997612
TI  - [Significance of the biological sciences in space and cosmos for the elementary
      science education].

PMID- 11997613
TI  - [The International Space Station in the 21st century: studies of space biology
      and future possibility of human beings].

PMID- 11997614
TI  - [Progress of the International Space Station program].

PMID- 11997615
TI  - Kinematic of animal locomotion under various gravitational fields.
AB  - A simple kinematic analysis of human locomotion under various gravitational
      fields is presented and a desirable way of locomotion is proposed. A comment on
      flight behaviors of insects in nongravity fields is also presented.

PMID- 11997616
TI  - [Can terrestrial living organisms adapt to microgravity?].

PMID- 11997617
TI  - [Basic study on multi-generation breeding of small fish in space].

PMID- 11997618
TI  - [Pre-flight ground studies for the Water Offset Nutrient Delivery Experiment
      (WONDER): a spaceflight payload comparing two nutrient delivery systems for plant
      growth in space].

PMID- 11997619
TI  - [Usefulness and limitations of clinostats].

PMID- 11997620
TI  - [Formation of asymmetric (correction of asymmetic) bioorganics by synchrotron
      radiation].

PMID- 11997621
TI  - [The ecology of microorganisms in closed environments--existing state and
      problems].

PMID- 11997622
TI  - [Involvement of mechanosensitive ion channels in regulation of plant shoot growth
      by gravity].

PMID- 11997623
TI  - [Role of microtubules in automorphic curvatures of rice coleoptiles under
      simulated microgravity conditions].

PMID- 11997624
TI  - [Auxin distribution and transport in the transition zone (peg region) between
      hypocotyl and root of cucumber seedlings].

PMID- 11997625
TI  - [Hydrotropism and differential expression of auxin-inducible genes in roots of
      cucumber seedlings].

PMID- 11997626
TI  - [Development of endodermal cells and expression of SCARECROW gene in weeping
      mutant of morning glory (Pharbitis nil)].

PMID- 11997627
TI  - [Analysis of circumnutation in the seedlings (correction of seedings) of
      agravitropic mutants].

PMID- 11997628
TI  - [Plant seeds exposed to high vacuum environment].

PMID- 11997629
TI  - [Rotational motion of flowering stalk in Spiranthes sinensis and its machinery].

PMID- 11997630
TI  - [Sedimentable amyloplasts in the secondary thickening growth region of stem of
      Japanese flowering cherry].

PMID- 11997631
TI  - [Growth of Avena seedlings under a low magnetic field].

PMID- 11997632
TI  - [Hypergravity-induced changes in gene expression in Arabidopsis].

PMID- 11997633
TI  - [Examination of growth environment for a long-term growth experiment of
      Arabidopsis thaliana. L on International Space Station].

PMID- 11997634
TI  - Theoretical analysis of mixed irradiation (3).
AB  - As the model we proposed last year was contradictory to experimental data, we
      revised again the models for mixed irradiation by Zaider and Rossi and by Suzuki,
      substituting a 'reciprocal-time' pattern of repair function for a first-order one
      in reduction and interaction factors of the models, although we used a second
      order repair function last year. The reduction factor, which reduces the
      contribution of the square of a dose to cell killing in the models, and the
      interaction factor, which also reduces the contribution of the interaction of two
      or more doses of different types of radiation, were formulated by using the
      'reciprocal-time' pattern of repair function. These newly modified models for
      mixed irradiation could express or predict cell survival more accurately than the
      older ones, especially when irradiation is prolonged at low dose rates. We
      present survival curves of cells calculated from the newly and the older models
      of assumptive simultaneous mixed irradiation with two or three types of
      radiation.

PMID- 11997635
TI  - [Depression of radiation-induced response by pre-irradiation with a low-dose
      rate].

PMID- 11997636
TI  - [Somatic mutation in epidermal cells of the larvae from Diapausing eggs of the
      silkworm, Bombyx mori, irradiated with heavy ion beam].

PMID- 11997637
TI  - [Cell killing and chromosomal damage in primary human bronchial epithelial cells
      irradiated with accelerated 56Fe ions].

PMID- 11997638
TI  - [Estimation for biological effects of heavy-ion exposure in space environment].

PMID- 11997639
TI  - [Repair systems for DNA damage by heavy-ion irradiation in meiotic cells].

PMID- 11997640
TI  - Heavy-ion induced chromatid break and repair kinetics in normal human
      fibroblasts.

PMID- 11997641
TI  - [Comparison of the balance sense nervous systems between 2 species of upside-down
      swimming catfish family].

PMID- 11997642
TI  - [A strategy for studying the physiology of amphibian larvae in microgravity].

PMID- 11997643
TI  - [Motility of alimentary tract of tadpoles at stepwise change in temperature].

PMID- 11997644
TI  - [Analysis of vertical eye movements of fish during linear acceleration].

PMID- 11997645
TI  - [Development and formation of otoliths in embryos and fry of mutant Medaka ha].

PMID- 11997646
TI  - [Gravity stress modulates pain sensation of rat via hypothalamus].

PMID- 11997647
TI  - [Changes of the abdominal aortic pressure in spontaneously hypertensive rats
      during parabolic flight].

PMID- 11997648
TI  - [Autonomic nervous responses under 3-dimensionally (correction of dimentinally)
      accelerated environment (II)--non contact measurement of surface pressure wave by
      a laser displacement sensor].

PMID- 11997649
TI  - [Heart rate variability spectral analysis during plasma apheresis with vaso-vagal
      reaction].

PMID- 11997650
TI  - [Influence on reproduction and growth in the mice passage bred in a 2G
      environment].

PMID- 11997651
TI  - [Effects for libido of male mice by change of gravity in parabolic flight].

PMID- 11997652
TI  - [Effect of parabolic flight on cytokine production in mice].

PMID- 11997653
TI  - Effect of gravity change on the production of thrombopoietic growth factors.
AB  - It is reported that the stay in the space develops anemia, thrombocytopenia, and
      altered function and structure of red blood cell. The mechanism of these
      abnormalities was not clarified yet. The cloning of the thrombopoietin (TPO),
      followed by the analysis of TPO and c-mpl (its cellular receptor) knockout mice
      confirmed its role as the primary regulator of thrombopoiesis. TPO has been shown
      to stimulate both megakaryocyte colony growth from marrow progenitor cells and
      the maturation of immature megakaryocyte to form functional platelet. This
      process includes the massive cytoskeletal rearrangement, such as proplatelet
      formation and fragmentation of proplatelet. In this study we have focused on the
      production of thrombopoietic growth factors in mice those were exposed to gravity
      change by parabolic flight (PF).

PMID- 11997654
TI  - [Modulation of cell mutability by serum factors from humans who experienced
      parabolic flight stress].

PMID- 11997655
TI  - Analysis of gene expression of lymphocytes in microgravity.
AB  - It has been reported that lymphocyte function decreases under microgravity.
      Though molecular mechanism of the immunosuppression in microgravity still remains
      enigmatic, it is suggested that gene expression of lymphocytes may be altered in
      microgravity. In this study we developed automatic flash-freezing equipment which
      can be utilized for exposing lymphocytes to microgravity by drop shaft
      experiments in Japan Microgravity Center (JAMIC). Gene expression profiles were
      analyzed by using DNA array in ground control lymphocytes and microgravity
      exposed lymphocytes.

PMID- 11997656
TI  - [Analysis of hypergravity response mediated by a cell-adhesive molecule, integrin
      in animal cells].

PMID- 11997657
TI  - [Increase of protease activity in cultured human cells exposed to gravity
      changing stress: involvement of proteases in modulation of cell mutability].

PMID- 11997658
TI  - [Gene expression in skeletal muscle of spaceflight rat].

PMID- 11997659
TI  - [Influence of hypergravity on cell proliferation and autogamy immaturity
      (correction of imaturity) of Paramecium tetraurelia].

PMID- 11997660
TI  - [Spatiotemporal properties of the bioconvection pattern formed by Tetrahymena and
      the effects of altered gravity on the pattern formation].

PMID- 11997661
TI  - [Geotaxis and ciliary movement in larva of Dicyemida].

PMID- 11997662
TI  - [Swimming behaviour and gravitational response of larva Heterobothrium okamotoi].

PMID- 11997663
TI  - Induction of cytochrome c release and apoptosis by Hck-SH3 domain-mediated
      signalling requires caspase-3.
AB  - The function of key components of signal transduction, the Src family tyrosine
      kinases is dependent on catalytic activity as well as on intermolecular
      interaction achieved by their SH2 and SH3 modular domains. We have analyzed the
      effect of overexpression of the hematopoietic cell kinase (Hck) and its N
      terminal unique and SH3 domains on cell survival. Overexpression of the N
      terminal unique and SH3 domains (Hck-USH3) induced about 25% of expressing Cos-1
      cells to undergo apoptosis 30 hrs after transfection. The full length p59 and p56
      forms and the unique domain alone induced low levels of cell death. The unique
      and SH3 domain of a closely related kinase, Lyn did not induce apoptosis.
      Overexpression of a mutant USH3 domain (Gly --> Ala), that disrupts membrane
      localization, did not induce high level of apoptosis. Cells overexpressing Hck
      USH3 showed activation of caspase-3 and release of cytochrome c from mitochondria
      into cytosol. Caspase-3 defective MCF-7 cells were resistant to apoptosis and
      cytochrome c release induced by Hck-USH3, which were restored by introducing the
      caspase-3 gene. These results suggest that Hck SH3 domain mediated signalling at
      the plasma membrane triggers a pathway leading to caspase-3 dependent cyto-
      chrome c release and apoptosis.

PMID- 11997664
TI  - The inherent cellular level of reactive oxygen species: one of the mechanisms
      determining apoptotic susceptibility of leukemic cells to arsenic trioxide.
AB  - Though reactive oxygen species (ROS) has been noticed to be involved in arsenic
      trioxide (As(2)O(3))-induced apoptosis of tumor cells, its role in apoptosis
      signaling remained to be elucidated. The objective of this work was to explore
      the association of the inherent cellular ROS level with the susceptibility of the
      tumor cells to apoptosis induction by As(2)O(3). Low concentration of As(2)O(3)
      was administered to cultured leukemic cell lines NB4, U937, HL60 and K562. The
      difference in apoptotic sensitivity was displayed among four cell types. ROS
      probes were incubated with the cells in the absence of As(2)O(3), and ROS was
      thus quantified relatively by flow cytometry. We manifested, in four cell types,
      the inherently existed difference in whole ROS quantity, and a positive
      correlation between the inherent ROS level and their apoptotic sensitivity to
      As(2)O(3). Furthermore, by interference using a ROS producer, we demonstrated
      that an elevation of ROS level would sensitize the cells to As(2)O(3)-induced
      apoptosis. The results of the present work suggested that the inherent ROS level
      might be determinative in tumor cells for their apoptotic susceptibility to
      As(2)O(3).

PMID- 11997665
TI  - The novel synthetic inhibitor of matrix metalloproteinases Ro 28-2653 induces
      apoptosis in Dunning tumor cells.
AB  - The effect of synthetic inhibitors of matrix metalloproteinases (MMP) has been
      shown against a variety of tumors in preclinical models. Ro 28-2653, a novel
      synthetic MMP inhibitor, is able to reduce tumor growth in orthotopic prostatic
      cancer in rats (R3327 Dunning tumor). However, at present this inhibitory
      mechanism in tumor inhibition in vivo can only be partly explained by the
      inhibition of the catalytic activity of MMPs overexpressed in cancereous tissue.
      Using the flow cytometric method, we have investigated the effect of various
      concentrations of Ro 28-2653 on the Dunning tumor cells with regard to the
      staining of F-actin and DNA as markers of apoptosis. In combination with
      fluorescence microscopy we detected the loss of F-actin and the degradation of
      internucleosomal DNA. This effect of Ro 28-2653 on apoptosis was dose- and time
      dependent increasing with concentration between 10 and 100 microg/ml as well as
      with time of treatment between 24 and 48 h.

PMID- 11997666
TI  - PDT effects of m-THPC and ALA, phototoxicity and apoptosis.
AB  - The purpose of this study was to estimate the efficacy of an endogenous
      sensitizer (delta-aminolevulinic acid (or ALA) induced protoporphyrin IX (or
      PpIX)) and an exogenous sensitizer (meta(tetrahydroxyphenyl)chlorin or m-THPC) on
      two different cell lines, rat colon adenocarcinoma PROb cells and murine melanoma
      B16A45 (B16) cells, in apoptosis production. After sensitizer incubation, cells
      were irradiated with an argon dye laser. LD(50) with m-THPC was 2.8 microg/ml and
      4.7 microg/ml under irradiation of 25 J/cm(2) respectively for PROb and B16
      cells. With ALA, LD(50) was 150 microg/ml and 175 microg/ml under 25 J/cm(2)
      respectively for PROb and B16 cells. Apoptosis induction by m-THPC or ALA-PDT was
      detected by DNA gel electrophoresis and quantified using an ELISA assay 24 h
      after PDT. The maximal apoptosis enrichment factor (MAEF) was reached for 6
      microg/ml m-THPC at 10 J/cm(2) for PROb and B16 cells and for 50 microg/ml ALA at
      25 J/cm(2) for PROb or B16 cells. Both m-THPC and PpIX are efficient
      photosensitizers and apoptosis inducers. However, MAEF is obtained by sensitizer
      or laser doses inducing very different phototoxic effects: MAEF was obtained
      after m-THPC-PDT with LD(78) for PROb cells and LD(30) for B16 cells and after
      ALA-PDT with LD(22) for PROb cells and LD(18) for B16 cells. However the overall
      m-THPC/PDT apoptotic induction (under the curve surface analysis) was not
      different whatever the cell line for 10 and 25 J/cm(2). On the contrary, ALA
      PpIX/PDT apoptotic induction was twice for 25 J/cm(2) as compared to 50 J/cm(2)
      (p < 0.01) for both the PROb and B16 cells. These results indicate that the
      apoptosis rate in PDT cell killing varies considerably according to cell type and
      sensitizer.

PMID- 11997667
TI  - Role of vitamins in determining apoptosis and extent of suppression by bcl-2
      during hybridoma cell culture.
AB  - The identification of cell culture media components that may instigate apoptosis
      in cell lines used for the production of commercial antibodies and recombinant
      proteins, is crucial to aid the development of improved media for reduced cell
      death and to understand the role of nutrient components in cell survival and
      maintenance. Here we determine the impact of depriving all or individual B-group
      media vitamins either, D-CaPantothenate (DCaP), choline chloride (CC), riboflavin
      (Rb), i-inositol, nicotinamide (NAM), pyridoxal hydrochloride (PyrHCl), folic
      acid (FA), or thiamine hydrochloride (ThHCl) on hybridoma cell growth and
      viability using fluorescence microscopy techniques. Cultivation in media deprived
      of all these vitamins prevented cell proliferation from reaching maximum capacity
      while increasing cell death rate, predominantly via apoptosis. Deletion of either
      DCaP, CC, or Rb showed that these components were most likely responsible for the
      development of apoptosis. Exclusion of either i-inositol, NAM or PyrHCl failed to
      inhibit cell growth and viability, while marginal improvements in viability were
      noted by ThHCl deprivation and more so by FA exclusion. Over-expression of the
      anti-apoptotic gene bcl-2 suppressed cell death initiated by all or single
      vitamin (either DCaP, CC or Rb) deprivation. The involvement of bcl-2 activity,
      established a close association between small vitamin molecules particularly
      DCaP, CC or Rb and the biochemical activation of apoptosis.

PMID- 11997668
TI  - Functional inactivation by interleukin-1beta of glyceraldehyde-3-phosphate
      dehydrogenase in insulin-secreting cells.
AB  - AIMS/HYPOTHESIS: It is well established that long-term exposure of isolated beta
      cells to cytokines [e.g., IL-1beta] results in increased expression of inducible
      nitric oxide synthase and subsequent release of nitric oxide, which in turn, has
      been shown to mediate a wide array of effects, including alterations in cellular
      high-energy metabolism. In this context, several extant studies have demonstrated
      significant reduction in adenine and guanine nucleotide triphosphate levels in
      beta cells exposed to IL-1beta. Herein, we examined the functional status of
      glyceraldehyde-3-phosphate dehydrogenase [GAPDH] in insulin-secreting cells
      exposed to IL-1beta, since it represents the first enzyme in the glycolytic
      pathway that is involved in the generation of ATP. METHODS: GAPDH was assayed
      spectrophotometrically in the cytosolic fraction derived from control and IL
      1beta -treated [300 pM for 24 hrs] insulin-secreting cell lines [HIT-T15 and
      RINm5F]. RESULTS: IL-treatment resulted in marked attenuation of GAPDH activity
      in HIT and RIN cells; such a reduction in this activity was not due to inhibition
      of its expression by IL-1. Instead, we observed that incubation of HIT and RIN
      lysates with peroxynitrite, a reactive intermediate of nitric oxide with
      superoxide anion, resulted in significant reduction in the GAPDH activity.
      CONCLUSION/INTERPRETATION: These results identify a GAPDH as one of the
      biochemical loci for the effects of IL-derived peroxynitrite in the islet beta
      cell. The previously reported reduction in high-energy phosphate levels in an IL
      treated beta cell may, in part, be due to inhibition of GAPDH activity, and
      subsequent reduction in the glycolytic efficiency of the beta cell.

PMID- 11997669
TI  - Molecular mechanisms of "detachment-induced apoptosis--Anoikis".
AB  - Apoptosis following loss of cell anchorage is of relevance for development,
      tissue homeostasis and disease. In the following the role of cell-matrix
      anchorage as well as cell-cell anchorage for cell survival and apoptosis is
      reviewed and the complex molecular mechanisms inducing and perpetuating
      detachment-induced apoptosis will be discussed with special emphasis on the role
      of caspases, p53, bcl-2 family members and the Fas signaling pathway.

PMID- 11997670
TI  - Death associated protein kinase: from regulation of apoptosis to tumor
      suppressive functions and B cell malignancies.
AB  - Death associated protein kinase (DAP-kinase) is a pro-apoptotic
      calcium/calmodulin-regulated serine/threonine kinase with a multidomain structure
      that participates in a wide array of apoptotic systems initiated by IFN-gamma,
      TNF-alpha, activated Fas, and detachment from extracellular matrix. At various
      stages during tumor development, cells are subjected to apoptosis inducing
      stimuli and genetic mutations causing inhibition of apoptosis confer a selective
      advantage to cells. Thus, apoptosis and its regulation play an important role in
      tumor initiation, progression and metastasis. It has been demonstrated that the
      tumor-suppressive properties of DAP-kinase operate at two different apoptotic
      checkpoints in the course of tumor development; first, during the early oncogene
      activated apoptotic checkpoint mediated by p19ARF-p53 pathway and second, during
      the late stages of metastasizing cells entering the circulation after detachment
      from extracellular matrix. Promoter hypermethylation of DAP-kinase has been
      observed in a high variety of primary tumors including head and neck tumors, and
      non-small cell lung cancers, where an association with poor prognosis was also
      noted. Notably, high frequencies of DAP-kinase methylation have been found in B
      cell lymphomas and myeloma, where loss of control of c-Myc induced
      hyperproliferation from inactivated DAP-kinase may possibly play an important
      role in the pathogenesis of these B cell neoplasms.

PMID- 11997671
TI  - Role of the CC chemokine receptor 9/TECK interaction in apoptosis.
AB  - Chemokine receptors are members of the G protein coupled receptor (GPCR)
      supergene family whose expression is highly restricted to hematopoietic cells.
      Although the primary role of chemokine and chemokine receptor interaction is
      believed to be regulation of chemotaxis of leukocytes, subsequent information
      clearly suggests that multiple immune regulatory functions are attributed to
      chemokine receptor signaling. We recently showed that activation of the CC
      chemokine 9 receptor (CCR9), a thymus-specific chemokine receptor, led to potent
      cFLIP(L)-independent resistance to cycloheximide-induced apoptosis and modest
      resistance to Fas-mediated apoptosis possibly via activation of multiple
      signaling components involving Akt and glycogen synthase kinase 3beta. The fact
      that these two apoptotic signals involve activation of similar arrays of death
      execution machinery such as caspase-8, caspase-9, or caspase-3, suggests that
      chemokine receptor signaling may provide a wide range of antiapoptotic activities
      to hematopoietic cells under certain biological conditions. GPCR is a large
      family of cell surface receptors, many of which are critically involved in
      hormonal and behavioral control. Recent observations also suggest that GPCR
      signaling plays a pivotal role in immune cell activation. Heterotrimeric G
      protein is an integral part of GPCR signaling. Thus, dissection of signaling
      components involved in the CCR9-mediated antiapoptosis could be a framework for
      cell survival mechanisms and may provide options for therapeutic interventions
      for neurdegenerative diseases or T cell malfunctioning.

PMID- 11997672
TI  - Aiolos and Ikaros: regulators of lymphocyte development, homeostasis and
      lymphoproliferation.
AB  - Aiolos and Ikaros encode hemopoietic-specific zinc finger transcription factors
      that are important regulators of lymphocyte differentiation. Aiolos and Ikaros
      play a critical role in regulating B and T cell development. Gene targeting
      studies in mice have shown that inactivation of Ikaros family proteins leads to a
      complete absence of T, B, NK and dendritic cells, whereas a reduction of Ikaros
      activity induce hyperproliferation and lymphomas. Aiolos knock-out mice have
      quantitatively normal lymphoid cells but have chronically activated B cells
      producing autoantibodies and develop lymphomas with increased frequency. These
      proteins are involved in the control of gene expression and, associated to
      nuclear complexes, participate in nucleosome remodeling. This protein family
      governs cell fate decisions and regulates homeostasis through complex isoforms
      expression and dimerization. Changes in this regulatory network may reflect
      differentiation and proliferation adjustments made in lymphoid progenitors and
      precursors. The direct involvement of aberrant Ikaros protein expression in human
      hematological oncogenesis, although suggested by several studies, remains to be
      settled at the genomic level. These points will be discussed in the present
      review.

PMID- 11997673
TI  - "Programmed death" in Schopenhauer's World?

PMID- 11997675
TI  - Professional liability 2002: res ipsa loquitor.

PMID- 11997676
TI  - Placental abruption.
AB  - Placental abruption complicates approximately 1% to 2% of all pregnancies and
      remains a significant cause of both maternal and fetal morbidity. Proposed
      pathophysiology of both acute placental abruption and the more common partial
      placental separation are discussed. The contribution of placental abruption to
      both preterm labor and preterm premature rupture of membranes is discussed.
      Recent evidence supporting maternal hypertensive disorders, maternal tobacco and
      cocaine use, age and parity, multiple gestations, maternal thrombophilias, and an
      unexplained elevated maternal serum alphafetoprotein as risk factors for
      abruption is reviewed. Emergency management of acute abruption is outlined.
      Finally, particular emphasis is given to the management of partial placental
      separation, including both immediate and delayed delivery and the use of
      tocolysis. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians.
      LEARNING OBJECTIVES: After completion of this article, the reader will be able to
      define the condition of placental abruption, list the conditions associated with
      abruption, and outline potential management options for patients with placental
      abruption.

PMID- 11997677
TI  - Phytoestrogens in the management of the menopause: up-to-date.
AB  - Despite the benefits of conventional hormone replacement therapy, some women are
      not candidates for this treatment and many others choose not to take it. As a
      result, there is growing interest among patients about natural alternatives.
      There is some evidence that phytoestrogens may offer protection against a wide
      range of human conditions, including breast cancer, cardiovascular disease, brain
      dysfunction, osteoporosis, and menopausal symptoms. The literature on the
      possible health benefits of phytoestrogens has expanded exponentially since the
      1980s, mainly in response to funding initiatives by the U.S. government and
      soybean industries, and more lately by European and UK Ministries of Food. The
      physiological effects of phytoestrogens also have created a marketing opportunity
      that has been used by industry, particularly in soybean-producing countries such
      as the U.S. and Australia. Nevertheless, clinical applications for phytoestrogens
      are still in their infancy, and more interventional trials are required to reach
      definitive conclusions regarding their efficacy and safety, although they appear
      to represent a promising group of compounds, which may be useful in the future
      for the treatment of the menopausal syndrome. Also, the lack of clinical data
      presently available must signal caution in relation to the possible risk of
      adverse effects. TARGET AUDIENCE: Obstetricians and Gynecologists, Family
      Physicians. LEARNING OBJECTIVES: After completion of this article, the reader
      will be able to identify the various types of phytoestrogens, list the sources of
      phytoestrogens, and summarize the various effects of phytoestrogens.

PMID- 11997678
TI  - Hormonal manipulations and breast cancer.
AB  - Breast cancer is the most common cancer among women and the leading cause of
      death in women, 40 to 55 years of age. The lifetime odds of developing breast
      cancer are apparently up to 1 in 8 women in North America and 1 in 12 in Western
      Europe. According to the American Cancer Society, some 200,000 women (and 1,500
      men) will be diagnosed with breast cancer this year. Although the incidence of
      breast cancer in women has been rising since the mid-1940s, the mortality has
      dropped modestly over the past decade, probably due to earlier and improved
      diagnosis and treatment. Evidence from both epidemiological and experimental
      studies points to an important role of reproductive variables in the development
      and promotion of human breast neoplasia. Hormonal manipulations, in the form of
      contraceptives, hormone replacement therapy, or antiestrogens, affect the
      incidence and course of breast cancer and may be useful in prevention and
      treatment of the tumor. In this review we summarize the current status of the use
      of hormones and antihormones in regard to breast cancer and outline possible
      areas of additional development and investigation. TARGET AUDIENCE: Obstetricians
      and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of
      this article, the reader will be able to summarize the effects of estrogen and
      progestogens on the breast and to list the effects of other hormonal modulators
      on the breast.

PMID- 11997679
TI  - What is special about the brains of musicians?

PMID- 11997680
TI  - Thyroid-beta2 and the retinoid RAR-alpha, RXR-gamma and ROR-beta2 receptor mRNAs;
      expression profiles in mouse retina, retinal explants and neocortex.
AB  - In neonatal retinal explants cultured long-term green cones are missing. Recently
      it was reported that thyroid hormone beta2 receptors (TR-beta2) are essential for
      these green cones to differentiate. Therefore transcript level of these receptors
      was investigated in our mouse retinal explants. However, thyroid receptors
      function as heterodimers with retinoid receptors (RR); so the fate of selected
      RRs was similarly analyzed using semi-quantitative RT-PCR. Loss of TR-beta2 and
      RR (RXR-gamma and ROR-beta2) mRNAs was observed after culturing the neonatal
      retina for 12 days. This indicates that these proteins are involved in
      determination of green cone identity. In addition, levels of the selected RR
      transcripts are differentially affected by short- or long-term culture. In the
      latter case an attached retinal pigment epithelium seems to play a protective
      role. Furthermore, divergent diurnal peaks of RR mRNAs are present in young as
      well as aged mouse retina and neocortex. This data might be relevant in the
      context of human ageing disorders.

PMID- 11997681
TI  - L-AP3 blocks rises in intracellular calcium associated with hippocampal CA1 LTP.
AB  - The involvement of type I metabotropic glutamate receptors in hippocampal CA1
      long-term potentiation (LTP) depends on the applied tetanic stimulation protocol.
      Activation of these receptors may cause an elevation of intracellular calcium via
      the formation of the second messenger inositol triphosphate (IP3) and subsequent
      intracellular calcium release. It has been shown that the type I metabotropic
      receptors antagonist L-2-amino-3-phosphonopropionate (L-AP3) blocks CA1 LTP.
      Combining dendritic calcium and field potential measurements in CA1 hippocampal
      area, we found that L-AP3 did not affect single calcium transients but reduced
      the calcium changes evoked by a single tetanus, preventing the long-lasting
      calcium enhancements associated with CA1 LTP. These findings suggest that the
      formation of this type of LTP requires calcium release from IP3-sensitive stores.

PMID- 11997682
TI  - Parvalbumin positive dendrites co-localize with apical dendritic bundles in rat
      retrosplenial cortex.
AB  - The granular retrosplenial cortex in rats, involved in learning and memory, has a
      highly modular organization in layer 1. Apical dendrites of layer 2 pyramidal
      neurons form bundles, which correspond to patchy thalamic input. Here, we
      demonstrate that dendrites of parvalbumin-immunoreactive (PV-ir) GABAergic
      neurons in layers 2/3 also form bundles, and that these co-localize in layer 1
      with the apical dendritic bundles, as verified by double immunofluorescence for
      PV and microtuble-associated protein. Deeper, at the border of layers 1/2, the PV
      ir bundles merge into a honeycomb-like structure, with walls consisting of PV-ir
      neuropil. Compartmentalization in layers 1/2 is characteristic of other
      periallocortical structures. Further work is necessary to determine whether these
      specializations may be specifically related to learning and memory.

PMID- 11997683
TI  - Neurotensin-induced modulation of dopamine D2 receptors and their function in rat
      striatum: counteraction by a NTR1-like receptor antagonist.
AB  - The present study investigated the neurotensin (NT) receptor subtype (NTR)
      involved in the antagonistic neurotensin modulation of striatal dopamine D2
      receptors observed in vitro and in vivo. The NT induced increase of the IC50
      values of dopamine (DA) competition for [125I]iodosulpiride binding sites was
      counteracted by the NTR1-like antagonist SR48692 in rat striatal slices.
      Intrastriatal perfusion of pergolide induced in the awake rat an inhibition of
      striatal DA release that was antagonized by NT. This action of NT was
      counteracted by co-perfusion with the NTR1 like antagonist SR48692. These data
      indicate that there exists in the striatum at the prejunctional level an
      intramembrane antagonistic NT receptor/DA D2 receptor-receptor interaction where
      NTR1 like receptor activation reduces the DA D2 autoreceptor function.

PMID- 11997684
TI  - Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to
      excitotoxicity.
AB  - Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a
      significant damage of cholinergic neurons concomitant with increased amyloid
      precursor protein (APP) expression in the cerebral cortex. However, the
      sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP
      expression in the damaged MBN are still elusive. Hence, we performed multiple
      labeling immunocytochemistry for choline-acetyltransferase (ChAT), neuron
      specific nuclear protein (NeuN) and APP 4, 24, and 48 h after NMDA infusion in
      the MBN. Whereas all cholinergic neurons were immunoreactive for NeuN, this
      neuronal marker also labeled a population of ChAT-immunonegative non-cholinergic
      neurons. Both neuron populations exhibited a similar degree of sensitivity to
      NMDA excitotoxicity that became evident as early as 4 h post-lesion. Cholinergic
      MBN neurons showed abundant APP immunoreactivity (approximately 90%), while only
      a fraction (approximately 20-30%) of non-cholinergic neurons expressed the
      protein. Remarkably, cholinergic but not non-cholinergic neurons retained their
      APP immunoreactivity after NMDA infusion. In conclusion, cholinergic MBN neurons
      are not preferentially sensitive to short-term excitotoxicity, but are one of the
      major sources of APP in the basal forebrain.

PMID- 11997685
TI  - Darkness beyond the light: attentional inhibition surrounding the classic
      spotlight.
AB  - The aim of the present investigation was to determine the nature and spatial
      distribution of selective visual attention. Using cortical source localization of
      ERP data corresponding to 60 task-irrelevant stimuli across the visual field, we
      assessed attention effects on visual processing. Consistent with previous
      findings, visual processing was enhanced at the attended spatial location. In
      addition, this facilitation of processing extended from the attended location to
      the point of fixation resulting in a region of facilitation. Furthermore, a large
      region of inhibition was found surrounding this region of facilitation. The
      latter result is inconsistent with a simple facilitative spotlight model of
      attention and indicates that attention effects can be both facilitatory and
      inhibitory.

PMID- 11997686
TI  - Spatial coincidence modulates interaction between visual and somatosensory evoked
      potentials.
AB  - The time course of interaction between concurrently applied visual and
      somatosensory stimulation with respect to evoked potentials (EPs) was studied.
      Visual stimuli, either in the left or right hemifield, and electric stimuli to
      the left wrist were delivered either alone or simultaneously. Visual and
      somatosensory EPs were summed and compared to bimodal EPs (BiEP, response to
      actual combination of both modalities). Temporal coincidence of stimuli lead to
      sub-additive or over-additive amplitudes in BiEPs in several time windows between
      75 and 275 ms. Additional effects of spatial coincidence (left wrist with left
      hemifield) were found between 75 and 300 ms and beyond 450 ms. These interaction
      effects hint at a temporo-spatial pattern of multiple brain areas participating
      in the process of multimodal integration.

PMID- 11997687
TI  - Enhanced amygdala responses to emotional versus neutral schematic facial
      expressions.
AB  - Human facial emotional expressions are complex. This may confound studies
      examining brain responses to these stimuli in control and clinical populations.
      However, several lines of evidence suggest that a few elementary facial features
      convey the gist of emotional expressions. Using fMRI, we assessed brain responses
      to line drawings of emotionally valenced (i.e. angry and happy) and neutral faces
      in healthy human subjects. Significantly increased fMRI signal was found in the
      amygdala, hippocampus and prefrontal cortex in response to emotional vs neutral
      schematic faces. Although direct comparisons of schematic and human faces will be
      needed, these initial results suggest that schematic faces may be useful for
      studying brain responses to emotional stimuli because of their simplicity
      relative to human faces.

PMID- 11997688
TI  - Interleukin-2 gene has superior antinociceptive effects when delivered
      intrathecally.
AB  - The antinociceptive effect of interleukin-2 gene on rat carrageenan-induced pain
      was explored using different delivery methods. Intrathecal (i.t.) or plantar s.c.
      delivery of plasmid harbouring the interleukin-2 gene produced a marked
      antinociceptive effect, which was maintained up to 6 days; the administration of
      recombinant human interleukin-2 only had a transitory effect. The antinociceptive
      effect lasted longer and was more potent when the interleukin-2 gene was
      administered i.t. than when delivered s.c. The effect of the interleukin-2 gene
      was related to its protein expression, was dose dependent, and could be
      potentiated by liposome. The results suggest that the interleukin-2 gene has a
      good prospect for clinical use.

PMID- 11997689
TI  - Self-organization of memory activity through spike-timing-dependent plasticity.
AB  - We studied the self-organization of memory-related activity through spike-timing
      dependent plasticity (STDP). Relatively short time windows (approximately 10 ms)
      for the plasticity rule give rise to asynchronous persistent activity of low
      rates (20-30 Hz), which is typically observed in delay periods of working memory
      task. We demonstrate some network level effects on the activity regulation that
      cannot be addressed in single-neuron studies. For longer time windows
      (approximately 20 ms), the layered cell assemblies that propagate synchronized
      spikes (synfire chain) are self-organized. Synchronous spike propagation was
      suggested to underlie the precisely timed spikes in the monkey prefrontal cortex.
      The present results suggest that the two networks for sustained activity are
      different realizations of the same principle for synaptic wiring.

PMID- 11997690
TI  - Modelling transfer characteristics of vestibular neurons in the fastigial nucleus
      of the behaving monkey on the basis of canal-otolith interaction.
AB  - The interaction of vestibular inputs with different dynamic and spatial behavior,
      i.e., canal-otolith interaction, leads to spatio-temporal convergence. Vestibular
      neurons in the fastigial nucleus often exhibit spatio-temporal convergence. The
      present report demonstrates that the discharge rates of most vestibular neurons
      in the primate fastigial nucleus can be simulated at different stimulus
      frequencies and orientations by a simple linear summation of the signals of the
      semicircular canals and the otoliths. In this way, a number of complex
      characteristics that depend on frequency, i.e. changing response-vector
      orientations, large phase changes, absence and presence of spatio-temporal
      convergence, can be easily explained.

PMID- 11997691
TI  - Transient activation of a somatosensory area in painful hallucinations shown by
      fMRI.
AB  - The disturbance of somatosensory perception and bodily experiences, including
      somatosensory hallucinations, are main features of the coenaesthesia sub-syndrome
      of schizophrenia. We used functional MRI to study a coenaesthesia patient with
      rapidly fluctuating painful somatosensory hallucinatory perceptions. Transient
      brain activations accompanying hallucinations were similar to the pattern
      elicited in a control experiment (non-painful tactile stimulation). However, an
      area in the medial parietal cortex, including parts of the precuneus and
      previously characterised as a supplementary sensory area, was activated
      significantly stronger during hallucinations than the control condition. This
      finding demonstrates elevated brain activity in a somatosensory area accompanying
      painful somatic hallucinations.

PMID- 11997692
TI  - Neuronal tissue polarization induced by repetitive transcranial magnetic
      stimulation?
AB  - In a blinded cross-over design, 10 healthy controls received 900 monophasic and
      biphasic repetitive transcranial magnetic stimuli over the primary motor cortex.
      Stimulation frequency was 1 Hz, and stimulation intensity 90% of the individual
      resting motor threshold. Suprathreshold stimuli applied at 0.1 Hz before and
      after repetitive stimulation controlled for changes in corticospinal
      excitability. We found a lasting corticospinal inhibition that was significantly
      more pronounced after monophasic than after biphasic repetitive transcranial
      magnetic stimulation (motor evoked potential amplitude reduced by 35 +/- 20% vs
      12 +/- 37%, mean+/- s.d.). We propose that the current flow in the coil plays a
      significant role in optimising after effects, and asymmetric current flow may be
      particularly efficient in building up tissue polarization.

PMID- 11997693
TI  - Comparison between SI and SII responses as a function of stimulus intensity.
AB  - In this MEG study we investigated the differences in responses to somatosensory
      electrical stimuli between primary (SI) and secondary (SII) sensory cortices
      using 10 different levels of stimulus intensity, starting from below the sensory
      threshold up to a weak painful level. SI dipole source linearly increased in
      amplitude as the stimulus intensity raised up to a strong motor level and then
      saturated at higher stimulation levels. The contralateral and ipsilateral SII
      dipole source strengths followed the stimulus intensity growing up to the motor
      threshold, but showed a decrease at the strong motor level, followed by an
      increase as the stimulus intensity raised towards the weak painful threshold.
      These results suggest different responses of SI and SII cortices as the intensity
      of stimulation rises from non-painful to painful values.

PMID- 11997694
TI  - Intrathecal CGX-1007 is neuroprotective in a rat model of focal cerebral
      ischemia.
AB  - The NMDA antagonist CGX-1007 (Conantokin-G) has previously been shown to possess
      potent neuroprotective properties when administered intracranially following
      experimental ischemic brain injury. Using the same model of middle cerebral
      artery occlusion (MCAo) in rats we now report the neuroprotective effects of CGX
      1007 when delivered intrathecally (i.t.). When given 4 h post-occlusion, a
      reduction in brain infarction was measured along with significant neurological
      recovery. Furthermore, we describe an i.t. neuroprotective therapeutic window
      lasting > or = 8 h from the start of the injury. Critically, this is the first
      comprehensive report of a neuroprotective agent that can be administered i.t. to
      ameliorate experimental brain injury and potentially provide an excellent
      therapeutic window as a neuroprotection treatment.

PMID- 11997695
TI  - Impact of progestins on estradiol potentiation of the glutamate calcium response.
AB  - One mechanism by which estrogen may modulate cognitive function is through
      potentiation of glutamate-mediated rises in intracellular calcium ([Ca2+]i) with
      resultant effects on neuronal morphology and signaling. Since progesterone is a
      component of hormone replacement therapy (HRT), we sought to determine whether
      therapeutically relevant progestins attenuated or blocked estrogen potentiation
      of glutamate-induced [Ca2+]i rises. 17beta-estradiol and progesterone, alone or
      in combination, significantly potentiated the rise in [Ca2+]i. When co
      administered, progesterone attenuated the estrogen response to the level seen
      with progesterone alone. In contrast, medroxyprogesterone acetate (MPA) had no
      effect when administered alone and completely blocked the 17beta-estradiol
      induced potentiation when co-administered. These results may have important
      implications for effective use of HRT to maintain cognitive function during
      menopause and aging.

PMID- 11997696
TI  - Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic
      action.
AB  - Typical antipsychotics (haloperidol) give rise to severe motor side-effects while
      atypical antipsychotics like clozapine do not. Action at several neurotransmitter
      receptors have been implicated. To identify the critical mechanisms involved we
      synthesized an 8-C1 isomer of clozapine which showed an equivalent affinity to
      clozapine on multiple receptors (5-HT1A, 5-HT2, D1, D4, M1) but differed in
      having a 10-fold higher affinity at the dopamine D2/3 receptor. When tested in a
      series of animal models indicative of the typical/atypical distinction
      (catalepsy, striatal gene-induction, prolactin elevation) isoclozapine lost
      atypical properties and behaved like a typical antipsychotic. Simultaneous in
      vivo receptor occupancy studies confirmed that alterations in D2 receptor
      occupancy were most closely related to loss of atypicality by clozapine's isomer
      isoclozapine. The implications for the design of future antipsychotics is
      discussed.

PMID- 11997697
TI  - Glutamate and NO mediation of the pressor response to 5-HT3 receptor stimulation
      in the nucleus tractus solitarii.
AB  - The possible participation of glutamate and NO/cGMP in the pressor response to 5
      HT3 receptor activation in the nucleus tractus solitarii (NTS) was investigated
      using selective antagonists in urethane-anaesthetized rats. Intra-NTS
      administration of NMDA and non-NMDA receptor antagonists, but not metabotropic
      glutamate receptor antagonists, markedly reduced (70%) the increase in blood
      pressure caused by local application of the potent 5-HT3 receptor agonist, 1-(m
      chlorophenyl)-biguanide. The 5-HT3 receptor-mediated pressor response was also
      significantly attenuated by the local blockade of nitric oxide synthase and
      soluble guanylyl cyclase. These data suggest that ionotropic glutamate receptors
      and the associated NO/cGMP transduction mechanism contribute downstream to the
      pressor effect elicited by 5-HT3 receptor stimulation in the NTS.

PMID- 11997698
TI  - Dorsal and ventral stream sensitivity in normal development and hemiplegia.
AB  - Form and motion coherence thresholds can provide comparable measures of global
      visual processing in the ventral and dorsal streams respectively. Normal
      development of thresholds was tested in 360 normally developing children aged 4
      11 and in normal adults. The two tasks showed similar developmental trends, with
      some greater variability and a slight delay in motion coherence compared to form
      coherence performance, in reaching adult levels. To examine the proposal of
      dorsal stream vulnerability related to specific developmental disorders, we
      compared 24 children with hemiplegic cerebral palsy with the normally developing
      group. Hemiplegic children performed significantly worse than controls on the
      motion coherence task for their age, but not on the form coherence task; however,
      within this group no specific brain area was significantly associated with poor
      motion compared to form coherence performance. These results suggest that
      extrastriate mechanisms mediating these thresholds normally develop in parallel,
      but that the dorsal stream has a greater, general vulnerability to early
      neurological impairment.

PMID- 11997699
TI  - Thrombin induces IL-10 production in microglia as a negative feedback regulator
      of TNF-alpha release.
AB  - Interleukin-10 (IL-10), an immunosuppressive cytokine, is produced by
      monocyte/macrophage lineage cells, T cells, and B cells in the immune system.
      Here, we show that thrombin induces IL-10 expression in cultured rat microglia.
      Thrombin treatment increases IL-10 mRNA expression after 3 h and IL-10 release
      into the culture medium 12 h after thrombin treatment. Neutralizing antibodies
      against IL-10 significantly enhanced TNF-alpha release from thrombin-treated
      microglia. IL-10 release was suppressed by an inhibitor of p38 MAPK, SB203580 but
      not by an inhibitor of ERK pathway, PD98059, whereas both SB203580 and PD98059
      inhibited TNF-alpha release. These results suggest that thrombin induces IL-10
      and TNF-alpha expression through different signaling mechanisms, and that IL-10
      inhibits TNF-alpha release as a negative feedback regulation.

PMID- 11997700
TI  - Trichloroethanol alters action potentials in a subgroup of primary sensory
      neurones.
AB  - We investigated the effects of 2,2,2-trichloroethanol (TCE), the active
      metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels
      (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2
      and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8
      fold of control, respectively. In 50% of the cells investigated (group A) the
      action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell
      outward-current was increased by 44%. Both effects could be antagonized by
      iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP
      duration. The effects of TCE in group A, which was 20-fold more potent than
      ethanol on BKCa channels and AP might contribute to the described analgesic
      effect of chloral hydrate.

PMID- 11997701
TI  - A subpopulation of efferent neurons in the mouse suprachiasmatic nucleus is also
      light responsive.
AB  - The suprachiasmatic nucleus (SCN) is the site of a circadian clock with input
      (afferent) pathways for photic entrainment and output (efferent) pathways for
      expression of overt, measurable rhythms. To determine whether there are
      individual neurons in the mouse SCN that might be part of both pathways, we
      performed double-label immunohistochemistry for light-induced c-Fos and the
      retrograde tracer cholera toxin subunit B (CtB), 2 weeks after CtB was
      iontophoresed into the subparaventricular area (subPVA). A minority of neurons
      was found that were both efferent to the subPVA and responsive to light. This
      cellular subset may function as a direct channel through the SCN for photic
      inputs to influence neural outputs, and its existence highlights the
      topographical heterogeneity of SCN tissue.

PMID- 11997702
TI  - Growth-associated protein 43 is up-regulated in the ganglion cells of the
      ischemic rat retina.
AB  - We investigated the expression and cellular localization of growth-associated
      protein (GAP)-43 in the rat retina following ischemia induced by transiently
      increased intraocular pressure. In the normal retina, GAP-43 immunoreactivity was
      restricted to profiles in the inner plexiform layer. Following ischemia and
      reperfusion, immunoreactivity appeared in ganglion cells. The cell density of
      labeled ganglion cells peaked three days post-lesion and then decreased at seven
      days. Quantitative evaluation by immunoblotting confirmed that GAP-43 expression
      increased at three days (to 190% of control levels) and then slightly decreased
      at seven days. Our findings suggest that some ganglion cells have the potential
      to regenerate through the up-regulation of GAP-43 in the ischemic rat retina.

PMID- 11997703
TI  - Truncated apoE forms tangle-like structures in a neuronal cell line.
AB  - Apolipoprotein E is the predominant brain lipoprotein and polymorphic variation
      in the APOE gene the major genetic susceptibly factor for late onset Alzheimer's
      disease (AD). Recently it was reported that carboxyl-truncated ApoE fragments
      induce tangle-like structures in neurons. We confirm the finding: in mouse
      neuroblastoma cells truncated apoE fragments lacking the carboxyterminus induce
      structures that have the appearance of neurofibrillary tangles. However these
      tangles are not induced in non-neuronal cells even in the presence of co
      expressed neurofilaments or tau. Further understanding of the basis of this cell
      specificity might add to understanding of the cell specificity of tangles in AD.

PMID- 11997704
TI  - Adrenergic control of glycemia in the paraventricular nucleus of the hypothalamus
      in pigeons.
AB  - The effects of local injections of adrenaline into the paraventricular nucleus
      (PVN) and into other anterior hypothalamic areas on blood glucose levels were
      investigated in conscious pigeons (Columba livia). Adrenaline evoked a reliable
      and potent increase in blood glucose levels when injected into the PVN; no
      glycemic change was observed after vehicle injections into the PVN or after
      adrenaline injections into the 3rd ventricle or hypothalamic structures adjacent
      to the PVN. Local pretreatment with propranolol, but not with phentolamine,
      abolished the adrenaline-induced hyperglycemia. The present results indicate that
      adrenergically mediated circuits into the avian PVN play an important role in
      central mechanisms of energy balance that may be equivalent to those observed in
      mammalian species.

PMID- 11997705
TI  - Developmental expression of progesterone receptor isoforms in the mouse midbrain.
AB  - Progesterone participates in the regulation of developmental processes in the
      brain and controls the function of distinct neural circuits. We have studied the
      expression of progesterone receptor (PR) isoforms in the developing and adult
      male and female mouse ventral midbrain. Transcripts of both receptor isoforms (PR
      A and B) were detectable pre- and postnatally but regulated differentially during
      ontogeny. Immunoblotting revealed that only the full-length form (PR-B) is
      transcribed transiently into protein, whereas the truncated PR-A isoform is not
      detectable as protein. Although the precise function of progesterone in the
      developing CNS is not fully understood, our data implicate a potential role for
      PR signaling for the developing nigrostriatal system.

PMID- 11997706
TI  - Selective disruption of the recognition of facial expressions of anger.
AB  - Appetitive aggression occurs in the context of resource/dominance disputes in a
      wide variety of species. Hence, the possibility arises that a specific neural
      system may have evolved to detect and coordinate responses to this specific form
      of challenge or threat. The dopamine system has been implicated in the processing
      of signals of aggression in social-agonistic encounters in several species. Here
      we report that dopaminergic antagonism in healthy male volunteers, following
      acute administration of the dopamine D2-class receptor antagonist sulpiride,
      leads to a selective disruption in the recognition of facial expressions of anger
      (signals of appetitive aggression in humans), but leaves intact recognition of
      other emotions and the matching of unfamiliar faces.

PMID- 11997707
TI  - Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go
      odor discriminations.
AB  - Recent evidence suggests that orbitofrontal cortex lesions cause an inability to
      withhold inappropriate responses particularly when learned behavior must be
      modified to reflect changes in the likely outcome or consequence of responding.
      By this account, orbitofrontal cortex should not be necessary for acquisition of
      simple discrimination problems, but should be critical for acquiring reversals of
      those problems. However, previous work in rats has shown orbitofrontal cortex to
      be critical for withholding responses even in a simple go, no-go discrimination
      task. Here we have reexamined the contribution of rat orbitofrontal cortex to
      acquisition and reversal of go, no-go odor discrimination problems. Contrary to
      prior reports, we found that rats with lesions of the orbitofrontal cortex
      acquired novel discrimination problems at the same rate as controls. Impairments
      were evident in lesioned rats when the response contingencies of the odors in the
      discrimination problem were reversed. These findings suggest that orbitofrontal
      cortex is not necessary for inhibiting responses unless responses must be altered
      to reflect changing relationships between cues and outcomes.

PMID- 11997708
TI  - Comparison of neural activity preceding reaches to auditory and visual stimuli in
      the parietal reach region.
AB  - We examined the responses of neurons in the parietal reach region (PRR) during
      reaches to the remembered locations of auditory or visual stimuli. We found that
      the firing rate of PRR neurons contained information about the location of
      auditory and visual stimuli. For neurons tested with visual stimuli, the amount
      of information remained constant throughout the task. In contrast, for neurons
      tested with auditory stimuli, the amount of target-location information increased
      as the trial evolved. During the reach period of the task, the amount of
      information that was carried by neurons tested with auditory stimuli was not
      statistically different from the amount carried by neurons tested with visual
      stimuli. We interpret these data to suggest that the type of information that PRR
      neurons encode evolves throughout a task.

PMID- 11997709
TI  - Cortical areas mediating stereopsis in the human brain: a PET study.
AB  - Using PET, we investigated the neural substrates of stereodepth perception in
      humans. The presentation of Julesz-type random-dot stereograms (RDS) produced
      significant rCBF elevations in Brodmann areas (BA) 18, 19 and 7, all in the right
      hemisphere. Activation foci were also found in both middle temporal areas (MT).
      These results demonstrate that, as in primates, cortical area MT and extrastriate
      areas are central to stereovision and that a network of predominant right
      hemispheric regions is recruited to meet visuo-spatial processing demands
      associated with horizontal binocular disparity inputs.

PMID- 11997710
TI  - Effects of musical training on speech-induced modulation in corticospinal
      excitability.
AB  - We investigated the effect of previous musical training on lateralization of
      language as indexed by the effects of reading aloud on the modulation of motor
      evoked potentials (MEPs) induced in the first dorsal interosseus muscles (FDI) by
      transcranial magnetic stimulation (TMS) of the primary motor cortex. We studied
      13 right-handed subjects, seven musicians who had been playing a musical
      instrument for >10 years and six controls who had never studied a musical
      instrument. In all subjects, the amplitude of MEPs in the right FDI was
      facilitated by reading aloud. However, the musicians also showed significant
      facilitation in the left FDI, while controls did not. These results illustrate
      striking effects of musical training on lateralization of motor and language
      functions.

PMID- 11997711
TI  - Humanin inhibits cell death of serum-deprived PC12h cells.
AB  - Humanin (HN) and S14G HN (HNG) are recently discovered polypeptides that rescue
      cells from death induced by multiple different types of familial Alzheimer's
      disease genes and by amyloid-beta. However, the cytoprotective activity of these
      peptides against other cell death-inducing stimuli remains unclear. In this
      study, we demonstrated, using three different methods (MTS assay, caspase-3
      assay, and detection of DNA fragmentation), that both HN and HNG protect PC12
      cells from death elicited by serum deprivation. This implies the potential of the
      peptides to rescue cells from a broad spectrum, if not all, of cell death
      inducing factors. Further investigations on HN may lead the possible application
      of this peptide as therapeutic agent for the treatment of other neurodegenerative
      diseases.

PMID- 11997712
TI  - BET, a novel neuronal transmembrane protein with multiple EGF-like motifs.
AB  - Using the signal sequence trap method, we have identified a cDNA clone coding for
      a type I transmembrane protein, BET, with 10 epidermal growth factor (EGF) motifs
      in the extracellular domain. In situ hybridization revealed that the bet mRNA is
      specifically expressed in the mitral/tufted cells in the olfactory bulb, Purkinje
      cells in the cerebellum, and pyramidal cells in the hippocampus. Using polyclonal
      antibodies, we have demonstrated that the BET protein is highly glycosylated and
      is localized in patches in the dendrites and in the somata of neurons. Since the
      predicted structure of BET shares many similarities with the Notch ligands, this
      novel protein may play crucial roles in establishing the neuronal networks in the
      olfactory system, cerebellum, and hippocampus. BET is the first transmembrane
      protein containing only multiple EGF-like repeats specifically expressed in the
      brain.

PMID- 11997713
TI  - Alternative transcripts of presenilin-1 associated with frontotemporal dementia.
AB  - We have analyzed the expression of Alzheimer's disease-associated presenilin 1
      (PS1) in various neurodegenerative disorders. Western blotting identified PS1 N-
      and C-terminal fragments similarly in the cortex of controls, Parkinson,
      Huntington and schizophrenia subjects. Additional PS1 immunoreactive species of
      42 and 46 kDa were present in six out of seven cases of sporadic frontotemporal
      dementia (FTD) and these were particularly prominent in two cases. RT-PCR
      analysis using nested primers showed the presence of PS1 gene products with
      deletions within the exon 4-8 region. Our results suggest that alternative
      transcription of PS1 may be associated with FTD.

PMID- 11997714
TI  - HLA class II DNA typing in a large series of European patients with systemic
      lupus erythematosus: correlations with clinical and autoantibody subsets.

PMID- 11997715
TI  - Effectiveness of directly observed therapy (DOT) for tuberculosis: a review of
      multinational experience reported in 1990-2000.

PMID- 11997716
TI  - Proposal for a new set of classification criteria for adult-onset still disease.

PMID- 11997717
TI  - Endemic mycoses in a cancer hospital.

PMID- 11997718
TI  - Immune reconstitution inflammatory syndrome: emergence of a unique syndrome
      during highly active antiretroviral therapy.

PMID- 11997719
TI  - Clinical epidemiology of Stenotrophomonas maltophilia colonization and infection:
      a multicenter study.

PMID- 11997720
TI  - Hyperammonemic encephalopathy.

PMID- 11997721
TI  - Advanced tools for digital EEG review: virtual source montages, whole-head
      mapping, correlation, and phase analysis.
AB  - Digital EEG allows one to combine recorded EEG channels into new montages without
      the need to record new data. Using spherical splines, voltages can be estimated
      at any point on the head. This allows one to generate various montages with the
      recorded or virtual electrodes at standardized locations, to interpolate bad
      electrodes, and to generate topographic maps over the whole head. Simulations of
      EEG activity originating in various brain regions are used to illustrate the
      effects of known generators on various montages and on whole-head maps. Some
      properties of spatial filters are introduced, and it is shown how they can be
      used to develop source montages with signals that estimate the activity in
      specific brain regions. The usefulness and validity of a source montage designed
      to focus on temporal lobe activity is illustrated with simulations and examples
      of temporal lobe spikes and seizures. Additional tools such as cross-correlation
      among channels, fast Fourier transform, and phase maps are described. These tools
      are useful in estimating time lags between source channels and in interpreting
      propagating spike and seizure activity. In combination, these tools help to
      analyze and to enhance activities that may be hard to detect from the background
      scalp EEG in traditional montages.

PMID- 11997722
TI  - Artifact correction of the ongoing EEG using spatial filters based on artifact
      and brain signal topographies.
AB  - Review and analysis of continuous EEG recordings may be impeded by physiological
      artifacts such as blinks, eye movements, or cardiac activity. Spatial filters
      based on artifact and brain signal topographies can remove artifacts completely
      without distortion of relevant brain activity. The authors describe the basic
      principle of artifact correction by spatial filtering and they review different
      approaches to estimate artifact and brain signal topographies. The main focus is
      on the preselection approach, which is fast enough to be applied while paging
      through the segments of a digital EEG recording. Examples of real EEG segments,
      containing epileptic seizure activity or interictal spikes contaminated by
      artifacts, show that spatial filtering by preselection can be a useful tool
      during EEG review. Advantages and disadvantages of the different spatial filter
      approaches are discussed.

PMID- 11997723
TI  - Computer-aided spatial classification of epileptic spikes.
AB  - The authors present a method that can be used to identify exemplar spikes from
      prolonged EEG recordings. To achieve this they have calculated single dipole
      source models for each automatically detected spike-like waveform. They used a
      dipole source algorithm that is computationally light and can be run on-line
      during EEG acquisition. Although a single dipole source model may not provide
      anatomically accurate information about the location of generators of all
      epileptiform abnormalities, it does provide a novel spatial parameter that may be
      useful in its own right. The authors use this spatial parameter and present the
      relative spatial density of the dipole locations in the form of three planar
      projections of the spherical model (a view from above, a view from the right, and
      a view from behind) and allow users to define the x-, y-, and z-coordinates of
      points of interest within the spherical model. They then present 10 example
      waveforms of events that have dipole source model locations that occur close to
      that seed coordinate. Overall, they found that this method performs very well for
      frequent events, but does not perform well for rare events or for diffuse EEG
      abnormalities.

PMID- 11997724
TI  - Digital tools in polysomnography.
AB  - Recent advances in the computing power and storage devices have made computer
      based recording of polysomnograms (PSGs) very attractive. Digital PSGs offer the
      possibility of automating many tedious and time-consuming tasks of identifying
      sleep related events. Automation not only alleviates these laborious tasks, but
      also introduces a measure of objectivity in the scoring of various discrete
      events. In this paper we briefly review some automatic methods that have been
      previously developed by the authors. Automatic sleep staging methods is
      emphasized with some illustrative results on inter-scorer variations. We also
      discuss the leg movement event, respiratory event, sleep spindle and rapid-eye
      movement detection methods.

PMID- 11997725
TI  - Introduction to hierarchical clustering.
AB  - Hierarchical clustering of spike events is a method of grouping events that are
      similar in topology, morphology, or both, and it provides a method of efficient,
      detailed analysis of interictal events. Information about the relative
      populations of spikes at multiple foci is presented, and artifact events are
      grouped and eliminated en masse. The process of hierarchical clustering is
      explained, and a set of simulated traces is used to illustrate the process of
      hierarchical clustering and the development of a cluster tree to display the
      relative populations of similar spike events. Using EEG data from long-term
      monitoring, the use of a "review wizard" is explored as a means of structuring
      the process of hierarchical clustering and traversing the cluster tree. This aid
      is also used to streamline the process of determining the similarity of events
      within each group and of verifying that events exhibiting clinically important
      differences are not hidden within the groups comprising the average traces.

PMID- 11997726
TI  - Outpatient EEG monitoring in the presurgical evaluation of patients with
      refractory temporal lobe epilepsy.
AB  - Most epilepsy centers obtain ictal EEG recordings to localize the epileptogenic
      zone during presurgical evaluations. Inpatient monitoring is standard practice
      but is expensive and can be inconvenient. The authors sought to determine whether
      outpatient monitoring can be safe and effective as the sole method of recording
      seizures in the presurgical evaluation of patients with refractory temporal lobe
      epilepsy. They reviewed the data of seven temporal lobectomy patients whose
      presurgical monitoring was performed entirely outside the hospital. Mean baseline
      seizure frequency was at least 9.1 seizures per week. An average of 7.4 seizures
      was recorded over 9.4 days of monitoring. Only one patient had any antiepileptic
      drug taper; none suffered any complications. After temporal lobectomy on the side
      of demonstrated ictal onset, postoperative follow-up averaged 5.5 years. At the
      most recent follow-up, all patients were either seizure free or had only rare
      disabling or nocturnal seizures (four patients had outcomes in Engel's class I
      and three patients in Engel's class II). A comparison group who underwent
      standard inpatient monitoring was similar in average seizure frequency,
      monitoring duration, number of seizures recorded, and postoperative outcome,
      although all but one had antiepileptic drugs tapered during monitoring. The
      authors conclude that there is a subset of patients for whom solely outpatient
      presurgical EEG monitoring can be used to help plan successful temporal
      lobectomy.

PMID- 11997727
TI  - Interictal EEG, hippocampal atrophy, and cell densities in hippocampal sclerosis
      and hippocampal sclerosis associated with microscopic cortical dysplasia.
AB  - The EEG characteristics of isolated hippocampal sclerosis (HS) and HS associated
      with other types of temporal lobe pathology are not well defined. The pathologic
      substrate may be an important variable in determining seizure-free outcome. The
      objective of this study was to define the distribution of epileptiform discharges
      in patients with HS and HS associated with microscopic dysplasia, and to examine
      their relationship with hippocampal atrophy and cell loss. Thirty-four patients
      (15 women and 19 men; mean age, 30.6 +/- 11.2 years), all with good outcomes
      after temporal lobectomy (Engel classes I and II), were included. The
      characteristics studied were frequency and distribution of spikes, MRI-based
      hippocampal volume ratios, and quantitative hippocampal cell density in various
      subregions. The isolated HS group showed a trend to a higher percentage of
      epileptiform discharges maximal at the anterior temporal electrodes (89.87 +/-
      17.0%; 79.5 +/- 28.2% in the dual-pathology group). The isolated HS group had, on
      average, significantly more cell loss (P < 0.001). There was a significant
      negative correlation between the amount of cell loss in the CA1 area and both
      anterior temporal spikes and hippocampal ratios (P < 0.05). Isolated HS and dual
      pathology show minimal differences in interictal spike distribution and
      frequency. More widespread spike distributions in severe isolated HS compared
      with patients with less cell loss is probably the result of less organized limbic
      circuitry.

PMID- 11997728
TI  - A hole in the skull distorts substantially the distribution of extracranial
      electrical fields in an in vitro model.
AB  - The purpose of this study was to quantify the distortion of electrical fields by
      skull foramina using an in vitro model. Extracranial voltage generated by current
      dipoles located inside a human calva immersed in saline were measured when a 4-mm
      hole was open and when it was blocked with paraffin wax. Dipoles were located
      either along the internal surface of the bone (superficial dipoles) or at
      increasing distances from the bone (deep dipoles). With the hole open,
      extracranial signals had a substantially greater amplitude than with the hole
      blocked. The locations of the largest voltage values recorded outside the skull
      depended on the distance of the recording electrode from the hole rather than on
      the location of the internal dipole. For superficial dipoles, voltage values with
      the hole open were as much as 116 times greater than when the hole was blocked.
      Furthermore, when the hole was open, the largest extracranial signals were seen
      at the hole even when the dipole was 5 to 6 cm away from the hole. The effects of
      skull holes were less prominent for deep dipoles than for superficial dipoles.
      Skull discontinuities can be major determinants for the distribution of
      extracranial EEG signals. These results have implications for EEG interpretation
      and for source localization.

PMID- 11997729
TI  - Periodic lateralized epileptiform discharges: etiology, clinical aspects,
      seizures, and evolution in 130 patients.
AB  - The purpose of this study was to analyze the clinical aspects in 130 patients
      presenting periodic lateralized epileptiform discharges (PLEDs) in their EEG and
      to compare these results with those found in the literature. Etiology, neurologic
      deficit, seizure occurrence, and evolution were studied in each patient by
      historical review. The recordings were obtained on 8- or 16-channel EEGs with
      electrode placement according to the International 10-20 System. Recordings
      containing PLEDs were selected. PLEDs were defined as repetitive periodic, focal,
      or hemispheric epileptiform discharges (spikes, spike and waves, polyspikes,
      sharp waves) usually recurring every 1 to 2 seconds. The statistical study was
      carried out via the chi(2) test using the computer program SPSS. The main
      etiology found in this group of patients was stroke (61 of 130 patients). Other
      processes found were brain infections, tumors, hematomas, and several other
      entities grouped together as miscellaneous (anoxic encephalopathy, subarachnoid
      hemorrhage, craniocerebral trauma, Creutzfeldt-Jacob disease, migraine, multiple
      sclerosis, and aminophylline intoxication). Half of these patients (65 of 130)
      developed seizures, mostly partial motor seizures. No significant relation
      between etiology and seizures was found (chi(2) = 2.81, P = 0.4222). Seizures
      recurred in 14 of 130 patients during a follow-up of 14.5 months. PLEDs were not
      recorded in any EEG at the time of seizure recurrence. PLEDs constitute a
      distinctive but uncommon EEG phenomenon of repetitive, periodic, and stereotyped
      lateralized complexes. In agreement with the literature, PLEDs were associated
      with an acute process and occurred early during the course of the illness in all
      patients studied and were usually associated with structural lesions, with stroke
      being the main etiology. Traditionally, seizures occur with PLEDs but it is also
      accepted that they can exist in patients who never develop epileptic activity,
      either clinically or electrically, as demonstrated in 50% of the patients
      studied. No significant association between seizures and any etiology could be
      found. It was not demonstrated that the occurrence of seizures may influence the
      outcome in any way.

PMID- 11997730
TI  - Decreased motor unit number estimates in juvenile myoclonic epilepsy.
AB  - In this study, motor unit number estimate (MUNE) analysis with McComa's technique
      was used to detect any change in lower motor neuron count in juvenile myoclonic
      epilepsy (JME). The study included 10 JME patients, 8 idiopathic generalized
      epilepsy (IGE) patients, 7 patients with mesial temporal sclerosis (MTS), and 15
      normal subjects. All the patients and normal subjects were subjected to MUNE
      analysis on the abductor pollicis brevis and tibialis anterior muscles, as well
      as needle electromyography and nerve conduction studies. Electromyographic and
      nerve conduction studies were normal in all groups. MUNEs in the JME group and
      were significantly lower than those of normal subjects (P < 0.001). MUNEs of IGE
      and MTS patients also tended to be lower than that of normal subjects with no
      significant difference from normal subjects. MUNEs of abductor pollicis brevis
      and tibialis anterior muscles were 114 +/- 24 and 90 +/- 15 for normal subjects,
      59 +/- 18 and 50 +/- 23 for JME patients, 91 +/- 22 and 75 +/- 19 for IGE
      patients, and 84 +/- 42 and 80 +/- 29 for MTS patients respectively. It may be
      reasonable to suggest that a genetic origin is responsible for a tendency to
      contract epilepsy, and the disorganization of lower motor neurons may be shared
      in JME.

PMID- 11997731
TI  - [A guessing game for our readers].

PMID- 11997732
TI  - [Cutaneous angiosarcoma of the head: three cases].
AB  - Cutaneous angiosarcoma of the head is an uncommon finding. We report three cases,
      two women with a scalp localization and a man with a facial (frontal)
      localization. Recurrence was observed in one woman after surgery; this patient
      was given palliative treatment due to her poor health condition. The other women
      experienced three recurrences. After the last surgery, latissmus dorsi free flap
      graft, she has been disease free. The man was treated with surgery and
      radiotherapy. Regional lymph node metastasis appeared 5 years after the initial
      treatment. He is now disease free after surgery and cervical radiotherapy. Wide
      surgery and careful long-term follow-up are essential. The latissimus dorsi free
      flap can provide successful cure.

PMID- 11997733
TI  - [Contribution of the semi-free radial forearm flap for head and neck
      reconstruction].
AB  - Flap failure is mostly caused by venous thrombosis of the anastomosis. The
      failure rate is higher in post-irradiated neck. To reduce the risk of venous
      thrombosis, the authors propose to harvest the radial forearm flap using the
      cephalic vein as the drainage vein and as a pedicle. Only a single arterial
      anastomosis is carried out. This technique has been described already in patients
      who underwent head and neck ablative surgery with radical neck dissection. The
      authors report 2 cases in patients with post-irradiated neck. The flap transfers
      were successful in the 2 cases. The operative time of harvesting this hybrid
      version is the same with the conventional free flap technique. This version of
      the radial forearm flap can be a method of choice for some complex microvascular
      reconstruction in the head and neck region.

PMID- 11997734
TI  - [Lengthening temporalis myoplasty].
AB  - Use of the temporal muscle to raise the lips is a very old technique. In 1934,
      Gillies folded the temporal muscle over the zygoma to the lip subcutaneously. In
      1952, MacLaughlin proposed to attach the temporal muscle tendon to the lips. With
      this aponeurotic relay there is a risk of lengthening and necrosis, the main
      cause of long-term failure. Taking inspiration from Maclaughlin, lengthening
      myoplasty lowers the temporal muscle as a whole descending the tendon to the lip,
      thus obtaining lengthening from the posterior part.

PMID- 11997735
TI  - [Chronic erosive gingivitis].

PMID- 11997736
TI  - [Management of cutaneomucosal herpes in the immunocompetent patient (excepting
      ocular manifestations) Short text--Societe Francaise de Dermatologie with the
      participation of l'ANAES].

PMID- 11997737
TI  - [Diffuse sclerosing osteomyelitis of the mandible and SAPHO syndrome].
AB  - BACKGROUND: Diffuse sclerosing osteomyelitis of the mandible (DSOM) and SAPHO
      (synovitis, acne, palmo-plantar pustulosis and psoriasis, hyperosteosis,
      osteitis) syndrome are not commonly associated. SAPHO has not been described to
      date in the stomatology and maxillo-facial surgery literature in French. Were
      report here a homogeneous series of 12 patients with DSOM. MATERIAL AND METHODS:
      All patients had mandibular osteitis. RESULTS: Five patients with multifocal
      osteitis wre considered to present SAPHO syndrome because of the associated skin
      lesions. One patient with a unique focus of mandibular osteitis and palmo-plantar
      pustulosis probably had early-stage SAPHO syndrome. The diagnosis in the other
      cases was diffuse sclerosis osteitis of the mandible. DISCUSSION: We compared our
      series with those reported in the literature, emphasizing diagnostic and
      therapeutic difficulties. Diffuse sclerosing osteomyelitis of the mandible should
      be distinguished from microbial osteitis. Early diagnosis is required to avoid
      successive and unnecessary dental avulsions. There is a possible link between
      DSOM and SAPHO and all patients should have a complete work-up including whole
      body scintigraphy to search for other foci. A biopsy is indicated to rule out
      malignancy. Nonsteroidal antiinflammatory drugs can improve patient comfort in
      this particularly long syndrome. Although the efficacy is demonstrated, surgery
      and antibiotics can only delay relapse for a few months.

PMID- 11997738
TI  - [Difficult surgical management of facial neurofibromatosis type I or von
      Recklinghausen disease in children].
AB  - We report a case of predominantly facial neurofibromatosis type I in a 7-year-old
      girl, exposing the difficulties encountered in surgical management. Infiltration
      of facial soft tissues by plexiform neurofibroma is difficult to control.
      Resection of large areas of facial skin is unconceivable, facial functions must
      be preserved. Orbitocranial surgery is reserved for orbital manifestations of
      neurofibromatosis with osseous sphenoid dysplasia and pulsatile exophthalmos.
      Despite progress in tumor imaging and surgery, facial neurofibromatosis remains a
      challenge for the surgeon. We discuss surgical technique and indications for
      surgery in these cases.

PMID- 11997739
TI  - [Craniofacial anthropometric patterns in genetic facial dysmorphism: methodology
      and applications].
AB  - Craniofacial anthropometric has become an important tool in medical genetics. The
      method is simple, non-invasive, reliable, and inexpensive. To provide reliable
      measurements, the method must be conducted with a precise procedure by a trained
      physician. Anthropometric determination of craniofacial morphology is helpful in
      identifying and describing syndromes associated with classical techniques.
      Additional studies may involve new approaches to facial morphogenesis.

PMID- 11997740
TI  - [Mandibular metastasis revealing thyroid carcinoma. Two cases].
AB  - Although thyroid cancer is not the first cause of bone metastases, this diagnosis
      must be always entertained because when it is found to be the cause of the
      metastasis, the survival is good. Bone metastases can take on different
      appearances and thyroid cancer discovered secondarily. We report two cases of
      mandibular metastases revealing a thyroid cancer and we stress on diagnosis and
      therapeutic difficulties.

PMID- 11997741
TI  - [Mandibular odontogenic carcinosarcoma: a case report].
AB  - The last W.H.O classification of odontogenic tumors (1992) individualized a new
      entity called odontogenic carcinosarcoma. We report a case in which we
      encountered some difficulties to establish the diagnosis. The patient J.Z., a 26
      year-old woman was operated on for a left mandibular tumor corresponding,
      histologically, to an ameloblastic fibrosarcoma. One year later, we noted a
      submandibular swelling considered as a local recurrence. After resection, the
      pathologic examination diagnosed a lymph node metastasis from the same tumor. We
      decided to observe the patient. Three years post operatively, metastatic lymph
      nodes appeared, involving a double-component tumor: ameloblastic fibrosarcoma and
      malignant ameloblastoma. These features allowed the diagnosis of odontogenic
      carcinosarcoma. We insist on difficulties of the diagnosis and the necessity of
      radical resection of the tumor with neck dissection.

PMID- 11997742
TI  - [Colchicine].

PMID- 11997743
TI  - [Orthognathic surgery in the Ivory Coast].

PMID- 11997745
TI  - [Childhood epilepsy syndromes and diseases].
AB  - The classification of seizures and epileptics syndromes made it possible on the
      prognostic level to differentiate the benign epilepsies and the serious
      epilepsies. In children, several concepts are to be considered for a better
      comprehension of the specificity of the epilepsies related to this age of the
      life: synaptogenesis, receptors ontogenesis and ionic channels, myelinogenesis,
      epigenesis. Epilepsy is often associated with cognitive disorders and behaviour
      disorders in children. The relations between cognitive functions and epilepsy are
      multifactorial with intrication of neurodevelopmental, environmental and
      psychogenic factors. Identification of epileptic syndromes genetically determined
      and genetic diseases becoming complicated by epilepsy, allow a complementary
      approach in the comprehension and diagnosis of childhood epilepsy.

PMID- 11997746
TI  - [Genetics en epileptology].
AB  - Recently, major advances have been obtained concerning the molecular genetic
      basis of Mendelian inherited epilepsies. Several responsible genes have been
      identified, leading to a better understanding of the pathophysiology of epilepsy,
      as well as new approaches in its diagnosis and treatment. However, several
      questions remain. Indeed, Mendelian epilepsies are rare and few patients are
      concerned. Despite several lines of evidence demonstrating the involvement of
      genetic factors in the common forms of epilepsy, no progress has been made in
      this field. Statistical and molecular strategies adapted to identify
      susceptibility genes for common epilepsies are now available. But these
      approaches require large samples of patients and relatives, and a collaborative
      network will be required for characterisation.

PMID- 11997747
TI  - [MRI exploration of partial epilepsy].
AB  - Investigative strategies for partial epilepsy have evolved greatly since the
      advent of morphological MRI. MRI currently provides the most extensive and
      sensitive information for detecting and localizing brain anomalies. Technical
      progress has included new sequences (3D acquisition, inversion-recovery, fast
      spin-echo), new imaging planes (through the greater diameter of the hippocampus
      for temporal epilepsy, orbitao-meatal for extra-temporal epilepsy), high
      resolution imaging, and better signal-noise ratio in addition to new procedurs
      such as NMR spectroscopy, diffusion/perfusion imaging, or functional MRI. One of
      the principal aims of MRI is to detect potentially epileptogenic brain anomalies
      useful for the detection and localization of the epileptic focus. MRI sensitivity
      is much greater than brain computed tomography, which excepting specific cases,
      is no longer contributive. Hippocampal sclerosis is a typical example of an
      epilepsy-related brain anomaly (mesial temporal lobe epilepsy) whose diagnosis
      has been changed by MRI. This entity was described by Bouchet and Cazauvieilh in
      1825 who related anatomic postmortem findings to the clinical expression.
      Reliable diagnosis of hippocampal sclerosis can now be achieved with MRI,
      contributing to the diagnosis of mesial temporal lobe epilepsy. MRI can also
      contribute precious prognostic information, useful for both drug and surgical
      treatment. It has been demonstrated that the degree of response to drug treatment
      is not univocal and that certain lesions such as hippocampal sclerosis are
      generally associated with drug resistance. Sensitivity to drug therapy also
      varies with the type of cerebral dysgenesia. It has also been demonstrated that
      the a brain lesion identified at MRI is generally a factor of good prognosis
      after surgery. Continuing improvements in MRI techniques, widespread availability
      of technical facilities and new derived techniques contribute greatly to the
      usefulness of MRI for investigating partial epilepsy.

PMID- 11997748
TI  - [Confusional disorders and epilepsy].
AB  - Confusion in an epileptic patient raises several diagnostic possibilities: non
      convulsive status epilepticus, interictal or post-ictal psychosis, drug-induced
      confusion, confusion of another nature. Accurate diagnosis is based on clinical
      analysis, systematically completed by the practice and the repetition of
      emergency EEG.

PMID- 11997749
TI  - [The behavioral disorders in epilepsy].
AB  - The behavioral disorders are more frequent in the epilepsy patients, children and
      adults, than in the general population. They have been extensively studied by
      numerous authors, as well as the underlying various factors. These factors are
      neurobiological and psychological. From the neurobiological point of view, the
      importance of the brain damages, their nature, their topography, their
      lateralization, their date of occurrence during the development have been
      underlined. Specific personality and behavior features have been linked to the
      temporal localization of the epilepsy, but many controversies continue about this
      topic and a behavioral temporal syndrome is not proven. The frontal epilepsies
      are also responsible for psychological and behavioral disturbances. The epilepsy
      per se is an etiologic factor, through the ictal events and the interictal
      changes in the neuronal functioning. One example is that of the endogenous
      production of opioid substances during the seizures. However the organic factors
      cannot be dissociated from the psychological ones. The neuropsychological
      deficits are significantly linked to the appearance of behavioral disorders in
      children. The stigma stuck to the epilepsy and the imprevisible character of the
      seizures have a deep resounding upon the subject, his family and his environment.
      The pharmacological medications are useful for the depressive and psychotic
      episodes, but have little efficacy on the character disorders, the aggressiveness
      and the psychogenic seizures. They need a careful assessment of the situation and
      a strict super vision of the seizure number (risk of worsening) and of the
      pharmacocinetic interactions. A comprehensive, social and psychological
      management of the epilepsy patients is always indicated, knowing that every
      person is unique and has to be understood and helped in his singularity.

PMID- 11997750
TI  - [Cognitive disorders in adult epilepsy patients].
AB  - Cognitive deficits are frequent in epileptic patients and can be considered as
      epileptic behavioral markers. They are assessed by a neuropsychological
      exploration that requires the use of standardized psychometric tests with well
      established goals, that will be discussed in this paper. The obtained
      neuropsychological data complement information provided by other investigations.
      The manifestation of cognitive deficits associated with epilepsy depends on a
      variety of factors in which some are specific to epilepsy. These disorders affect
      in certain cases the intellectual functioning as well as other aspects of
      cognition, as emphasised in this paper, and may be accentuated by medically
      intractable seizures.

PMID- 11997751
TI  - [New antiepileptic drugs: new therapeutic options].
AB  - Introduction of new generation antiepileptic drugs on the French market has
      considerably diversified our conventional therapeutic schemes for epilepsy. New
      arrivals, topiramate, tiagabine and oxcarbazepine, will further amplify these
      changes. Compared with conventional drugs, these new products present more
      favorable pharmacokinetic properties, with no or very weak interactions and
      better tolerability, especially concerning cognition. These new agents should be
      used in accordance with their spectrum of activity, which depends on their
      mechanism of action. In add-on trials in partial epilepsy patients, all these new
      products have shown efficacy in partial and secondarily generalized seizures.
      Seizure frequency is reduced by at least 50% in 30 to 50% of the patients. Some
      of these drugs have a broader spectrum, also exhibiting efficacy for the
      different seizure types of generalized, symptomatic or idiopathic epilepsy.
      Gabamimetic agents may have worsening effects in some patients with generalized
      epilepsy, especially with absence or myoclonic seizures. The most obvious
      benefits, some patients become seizure-free, are obtained in patients with
      intermediate severity given a two-drug regimen including one of these new agents.
      For children progress has been less rapid but prognosis, including cognitive
      outcome, has been considerably improved, for example in infantile spasms with
      vigabatrin and in Lennox-Gastaut syndrome with lamotrigine and felbamate, the
      latter drug being highly toxic. For the moment in France, authorities have
      limited the use of all these new antiepileptic drugs to adjunctive therapy for
      epilepsy resistant to conventional drugs. Recent monotherapy data have however
      demonstrated similar efficacy and better tolerability. Once the pivotal,
      controlled studies have enabled regulatory approval, all these compounds will
      have to undergo large-scale evaluation in order to better define dosages, long
      term tolerability, indications and possible contra-indications in the various
      epileptic syndromes, including childhood epilepsy.

PMID- 11997752
TI  - [The presurgical evaluation of epilepsies].
AB  - In this article, we present an overview of the principles, practices and
      procedures of the presurgical evaluation of the epilepsies in use in our center
      and in the majority of French teams. Surgery for epilepsy is offered to patients
      presenting with severe epilepsy with partial seizures. Its aim is to stop the
      seizures, or to significantly reduce their frequency. To do that, the 
      epileptogenic zone  should theoretically be removed and/or the propagation
      pathways of the seizures should be cut. Discussion of these indications
      inevitably includes prior assessment of the functional sequels (sensory, motor,
      cognitive or behavioral) which surgery is liable cause. The presurgical
      evaluation involves a multidisciplinary approach involving epileptologists,
      neurophysiologists, neuroradiologists, neuropsychologists and neurosurgeons and
      is carried out in two phases. The phase I is based on non-invasive
      investigations, including functional and structural neuroimaging,
      neuropsychological assessment, source localization of interictal spike and video
      EEG recordings of seizures. The phase II is often required and is aimed to
      precisely define the anatomical localization of the epileptogenic zone and the
      relationships with a structural lesion. This invasive phase is mainly based on
      stereoelectroencephalography (SEEG). Finally, the surgical procedure must be
      adapted according to the distribution and dynamics of the anatomical and
      functional abnormalities which individually define each case of epilepsy.

PMID- 11997753
TI  - Study cast assessment.

PMID- 11997754
TI  - Evaluating posterior occlusion.

PMID- 11997755
TI  - Early treatment conference alters clinical focus.

PMID- 11997756
TI  - "Two" much of a good thing? Then let's pick one slot size and make it metric.

PMID- 11997757
TI  - Dental morphologic characteristics of normal versus delayed developing dentitions
      with palatally displaced canines.
AB  - An earlier study reported on the delayed dental age in about 50% of patients with
      palatally displaced canines (PDC), suggesting the possible existence of 2
      different PDC phenotypes. The present study aimed to determine whether the PDC
      subgroup with late dental age displays different dental features from the PDC
      subgroup with normal dental age, supporting the above assumption. The 3 dental
      parameters examined were mesiodistal and buccolingual tooth sizes, the presence
      of anomalous maxillary lateral incisors, and other congenitally missing teeth.
      Fifty-eight subjects with PDC, 37 girls and 21 boys, were divided according to
      dental age and compared with age- and sex-matched controls. The results revealed
      marked sexual dimorphism. Delayed dental development was twice as prevalent among
      the PDC males. The existence of 2 distinct PDC subgroups was supported for males
      only. One subgroup was characterized by delayed dental development, smaller-than
      average teeth, and a marked increase in the prevalence of anomalous lateral
      incisors. The second subgroup more closely resembled the controls, presenting a
      timely developed dentition, a moderate and nonsignificant increase of anomalous
      lateral incisors, and a reduction in the dimensions of only the central incisors
      and the first molars. In females, although the prevalence of anomalous lateral
      incisors was slightly increased in the late dental age subgroup, tooth sizes were
      remarkably similar, negating the existence of 2 distinct subpopulations. Studying
      the overall PDC group as a single entity produced confusing results because
      important differences were obscured when the 2 sexes and the 2 dental age
      subgroups (in males) were combined.

PMID- 11997758
TI  - Duration of nutritive and nonnutritive sucking behaviors and their effects on the
      dental arches in the primary dentition.
AB  - The purpose of this study was to determine the association between the duration
      of nutritive and nonnutritive sucking behaviors and various occlusal
      characteristics in the primary dentition. Sucking behavior data were collected on
      372 children followed longitudinally from birth by using periodic questionnaires
      completed by parents. Study models were obtained from the children at 4 to 5
      years of age and assessed for posterior crossbite, anterior open bite, and
      overjet. Dental arch parameters including arch widths, arch lengths, and arch
      depths were measured directly from the models. The subjects were grouped
      according to type of habit (pacifier or digit) and duration of nonnutritive
      sucking behaviors (less than 12, 12 to 24, 24 to 36, 36 to 48, and more than 48
      months). Children with nonnutritive sucking of less than 12 months were further
      grouped according to the duration of breast-feeding. The dental arch and the
      occlusal characteristics were then compared among these groups. The results
      indicated no relationship between duration of breast-feeding during the first
      year of life and any dental arch or occlusal parameters. The study found that
      prolonged pacifier habits resulted in changes to the dental arches and the
      occlusal parameters that were different from the effects of digit sucking. In
      addition, some changes in the dental arch parameters and occlusal characteristics
      (eg, prevalence of posterior crossbite and increased amount of overjet) persisted
      well beyond the cessation of the pacifier or digit habit. Although further study
      is needed to determine the effects of nonnutritive sucking behavior in the mixed
      dentition, the results suggest that current recommendations for discontinuing
      these habits may not be optimal in preventing habit-related malocclusions.

PMID- 11997759
TI  - Evaluation of antegonial notch depth for growth prediction.
AB  - In recent years, some researchers have proposed that the depth of the mandibular
      antegonial notch can be used as a predictor of facial growth. However, the data
      for those studies were derived from populations with extreme morphologic
      characteristics. The purpose of this investigation was to test the hypothesis
      that the antegonial notch depth is a useful predictor of facial growth in a
      longitudinal sample of untreated growing patients selected at random. Lateral
      cephalometric radiographs were obtained from 20 males and 20 females at 3 times,
      approximating prepubescence (8.5 years), adolescence (12 years), and adulthood (>
      or = 17 years). These 40 subjects were randomly chosen from a longitudinal sample
      of untreated growing patients. Prepubescent and adolescent antegonial notch
      depths were correlated with vertical and horizontal growth changes of the jaws
      from the age of 8.5 years to adulthood. Correlation analysis revealed a
      statistically (but not clinically) significant negative relationship (0.40 < or =
      r < or = 0.47; P < or =.05) between adolescent antegonial notch depth and
      horizontal growth of the maxilla and the mandible from adolescence to adulthood.
      Previous investigators have proposed that antegonial notch depth, when extreme in
      magnitude, might be used to predict facial growth. We concluded that antegonial
      notch depth fails to provide sufficient indication of future facial growth to
      warrant its application as a growth predictor in a nonextreme population.

PMID- 11997760
TI  - Estimated natural head position and facial morphology.
AB  - Estimated natural head position, or natural head orientation (NHO), has been
      proposed as a preferred reference position for assessing facial morphology.
      However, because this position is subjectively defined by the orthodontist, it
      could be influenced by facial form, which would be an undesirable attribute. The
      aim of this study was to assess whether NHO is influenced by facial morphology.
      Lateral photographs of 14 patients were used. Each was warped to produce 2 new
      images, with the chin positioned backwards or forwards relative to the original
      (+/-2 degrees change of the soft tissue N-Pg line). All 42 images were placed in
      circular frames and shown to 7 experienced orthodontists, who were asked to
      orient them to NHO. Image orientation between the 3 chin positions was measured
      and compared. The results showed that NHO depended on chin position. Images with
      protrusive chins were positioned with the head rotated more downwards (Frankfort
      plane 3.10 degrees relative to horizontal) than were images with retrusive chins
      (Frankfort plane 4.98 degrees ). The difference in head orientation measurements
      was half of the difference in chin position (1.88 degrees for a chin change of 4
      degrees ). These findings call into question the validity of NHO for diagnosis
      because it depends on the same factor it aims to assess. Use of NHO would result
      in underestimating the true skeletal relationships.

PMID- 11997761
TI  - Computed tomography evaluation of temporomandibular joint alterations in class II
      Division 1 subdivision patients: condylar symmetry.
AB  - Thirty persons ranging from 12 years 8 months to 42 years of age with Class II
      Division 1 subdivision malocclusions underwent computed tomography of the
      temporomandibular joints. The images obtained from axial slices were evaluated
      for possible asymmetries in size and position that may exist between the condylar
      processes associated with this malocclusion. Paired Student t tests were applied,
      and Pearson product moment correlations were determined after measurements on
      both Class I and Class II sides were obtained. The results of this study showed
      no statistically significant asymmetries between the condylar processes evaluated
      in this sample.

PMID- 11997762
TI  - Growth and treatment changes in patients treated with a headgear-activator
      appliance.
AB  - The aim of this study was to investigate growth and treatment changes in patients
      with Class II Division 1 malocclusion treated with a combined headgear-activator
      appliance. The sample consisted of 20 consecutive male patients treated with
      headgear-activator. Their compliance was checked after 2 months of treatment, and
      3 patients dropped out. Lateral cephalograms, obtained 6 months before treatment,
      at the start of treatment, after 6 and 12 months of treatment, and 24 months
      after treatment, were analyzed by the method of Pancherz. The results disclosed
      that during growth, on average, overjet, molar relationship, and jaw-base
      relationship improved, and the mandibular incisors became retruded; the changes
      were statistically significant over a 2-year period. There was no significant
      change in the overbite. During the 12 months of treatment, there was no maxillary
      forward growth, and the jaw relationship improved (P <.001) because of forward
      growth of the mandible (P <.001). The molar relationship and the overbite
      improved (P <.001). Significant treatment effects included reduction in overjet
      (P <.001) and overbite (P <.01), and improvement of jaw-base (P <.05) and molar
      (P <.001) relationships. There was significant restraint of maxillary forward
      growth (P <.05). The eruption of the maxillary incisors and molars was restrained
      (P <.05). The average basic growth pattern in Class II Division 1 malocclusion
      resulted in small favorable changes in overjet, molar relationship, and jaw-base
      relationship. The main effect of the headgear-activator appliance was a favorable
      dental change, limited to restraint of maxillary forward growth but not affecting
      the vertical dimension.

PMID- 11997763
TI  - Experimental tooth movement through mature and immature bone regenerates after
      distraction osteogenesis in dogs.
AB  - The purpose of this study was to verify the influence of tooth movement on tooth
      roots and periodontal tissues when teeth were moved into mature, well-organized,
      and mineralized regenerate bone created after distraction osteogenesis compared
      with immature, fibrous, and less-mineralized bone. Six 15-month-old male beagles
      underwent 10 mm of bilateral mandibular distraction osteogenesis. After 2-week
      (group 1) and 12-week (group 2) consolidation periods, third premolars were moved
      distally into the regenerate bone with 100 g of orthodontic force for 12 weeks.
      Simultaneously, second premolars were also moved distally as controls. After
      completion of tooth movement, the experimental animals were killed, and their
      tissues were harvested for histological evaluation. When premolars in groups 1
      and 2 were compared, group 1 showed higher rates of tooth movement until the
      eighth week of experimental tooth movement (P <.05). The amount of tooth movement
      was significantly greater in group 1 than in group 2 or in the control teeth (P
      <.05). In group 1, we observed considerable root resorption extending into the
      dentin, and the thickness of the dentin became approximately half that of the
      controls at the compression side adjacent to the distraction gap. This root
      resorption extended from the cementoenamel junction to the root apex. In group 2,
      root resorption on the compression side reached the dentin, but the root
      resorption was less than in group 1. These results indicated that heavy force and
      early orthodontic tooth movement are not recommended when teeth are moved through
      regenerated bone created by distraction osteogenesis, to avoid tipping and severe
      root resorption.

PMID- 11997764
TI  - Orthodontic treatment outcome in a First Nations population in Alberta, Canada: a
      comparative study.
AB  - The primary objective of this study was to determine whether there was a
      significant difference in the degree of improvement after orthodontic treatment
      between a sample of First Nations orthodontic patients and a control sample of
      non-First Nations orthodontic patients. The secondary objective was to determine
      whether there was a difference in the severity of malocclusions being treated in
      a sample of the First Nations patients compared with a control sample of the non
      First Nations patients. Several factors that might affect treatment outcome, such
      as missed appointments, treatment duration, oral hygiene, extractions, dental
      classification, and geographic location, were also studied. A sample of 60 First
      Nations patients and a control group of 60 non-First Nations patients between the
      11 and 18 years of age who had been treated with full fixed orthodontic
      appliances were evaluated. The weighted peer assessment rating (PAR) index was
      applied to pretreatment and posttreatment study models to address the study's
      main objectives. The results showed that the First Nations group had greater PAR
      scores pretreatment than did the controls, and their weighted PAR scores improved
      more with treatment. Posttreatment PAR scores were similar between the 2 groups.
      In addition to First Nations status, only extractions and geographic location
      affected PAR improvement scores.

PMID- 11997765
TI  - The reconstruction of bilateral clefts using endosseous implants after bone
      grafting.
AB  - This article presents the orthodontic reconstruction of an adult bilateral cleft
      patient with a severe Class III malocclusion in which endosseous implants were
      inserted after secondary alveolar bone grafting. The patient was a 21-year-old
      Japanese male whose lateral incisors were congenitally missing and whose
      premaxilla was inclined lingually. The occlusion was classified as Angle Class
      III with an overjet of -8 mm. Orthodontic alignment was initiated to correct the
      position of the maxillary incisors before bone grafting. After the anterior
      occlusal relationship was corrected, bilateral alveolar clefts were reconstructed
      by bone grafting with autogenous particulate marrow and cancellous bone harvested
      from the iliac crest. ITI-SLA fixtures (Institute Straumann, Waldenburg,
      Switzerland) (length, 10 mm; diameter, 4.1 mm) were placed into the grafted bone
      for prosthetic restoration of the missing lateral incisors. The results
      illustrate that this protocol can be expected to provide an acceptable occlusion
      and good dentoalveolar stability in adult cleft patients.

PMID- 11997766
TI  - Treatment of a class I crowded malocclusion.

PMID- 11997767
TI  - Accuracy of patient reporting as an indication of headgear compliance.
AB  - Orthodontists struggle daily with the issue of patient compliance. Often, we must
      rely on patient cooperation with headgear to correct Class II malocclusions.
      Because there is no way to objectively and accurately gauge headgear cooperation,
      we must look for clues in assessing compliance. One clue that we use is the
      patient's own reporting of headgear wear. This study was aimed at determining the
      accuracy of patient reporting. Twenty patients in a private orthodontic practice
      were supplied with electronic timing headgears that enabled the author to compare
      their reported hours of headgear use with electronically measured actual usage.
      In this sample, 69% of the patients reported their headgear use at an accuracy
      level of 84% or greater, while 31% reported their use at an accuracy level of 58%
      or less. If fully one third of our patients are significantly inaccurate in
      reporting headgear use, this has clear implications in patient education,
      expected treatment results, and informed consent. Some may consider the timing
      headgear a useful adjunct in promoting better patient compliance.

PMID- 11997768
TI  - A web-based cleft lip and palate registry.

PMID- 11997769
TI  - Litigation, legislation, and ethics. Location, location, location.

PMID- 11997771
TI  - Management of common voice problems: Committee report.
AB  - OBJECTIVE: This report provides the reader with a state-of-the-art update on a
      number of common voice problems that require phonosurgical intervention. STUDY
      DESIGN AND SETTING: This multiauthor review is not a position statement of the
      American Academy of Otolaryngology-Head and Neck Surgery (AAOHNS) and may reflect
      institutional preference and/or bias. It arose from a panel discussion at the
      AAOHNS meeting in 2000. RESULTS: We provide a review of the genesis and
      management of papillomatosis, dysplastic glottal epithelium, arytenoid
      granulomas, Reinke's edema, and vocal-fold paralysis. CONCLUSIONS AND
      SIGNIFICANCE: In the past decade, there has been a dramatic expansion of
      knowledge regarding a variety of voice disorders and associated treatment. There
      has been a convergence of basic science investigations in anatomy, physiology,
      and pathology with clinical trials of treatment, both surgical and nonsurgical.
      This information should provide the reader with current insight into critical
      management issues of the aforementioned disorders.

PMID- 11997772
TI  - Surgery for pediatric vocal cord paralysis: a meta-analysis.
AB  - OBJECTIVE: The study goal was to determine the impact of various surgical
      procedures for bilateral vocal cord paralysis in children by using established
      principles of meta-analysis. STUDY DESIGN AND SETTING: We conducted a
      retrospective review of the literature in which a predetermined protocol was used
      to identify articles for meta-analysis. Six articles met inclusion criteria, and
      pertinent data were extracted. RESULTS: Pooled data analysis demonstrated primary
      procedure-specific decannulation rates for external arytenoidopexy for 19 of 24
      (79%), external arytenoidectomy for 14 of 19 (74%), CO2 laser arytenoidectomy for
      4 of 10 (40%), and costal cartilage graft procedures for 2 of 2 (100%). External
      arytenoid procedures are more efficacious than CO2 laser procedures in terms of
      primary decannulation (P = 0.02). CONCLUSION: Meta-analysis of the existing
      literature reveals that external arytenoidopexy and external arytenoidectomy are
      equivalently effective procedures and that the two combined are significantly
      more effective than CO2 ablative procedures. SIGNIFICANCE: External procedures
      appear to be more effective as a first-line treatment in pediatric vocal cord
      paralysis, with arytenoidopexy with or without partial arytenoidectomy offering
      an attractive first-line surgical option.

PMID- 11997773
TI  - Management and outcome of early glottic carcinoma.
AB  - OBJECTIVE AND STUDY DESIGN: We designed a retrospective study to analyze
      treatment methods and outcomes for patients with lesions ranging from carcinoma
      in situ to invasive T1 glottic squamous cell carcinoma. Patients with nonsquamous
      cell carcinoma, verrucous variant of squamous cell carcinoma, anterior commissure
      involvement, and T2 lesions were excluded. SETTING: University of Pittsburgh
      School of Medicine, a tertiary referral center. RESULTS: Fifty-four patients met
      the inclusion criteria. Mean follow-up was 49 months (range 24 to 96 months).
      Forty-eight of 54 (89%) were treated with endoscopic excision. Forty of these 48
      patients (83%) were successfully treated with endoscopic excision(s) as the only
      treatment modality. Four patients had persistence of disease despite multiple
      endoscopic excisions. Two of these patients underwent hemilaryngectomy, 1
      received radiation treatment, and 1 received radiation therapy followed by a
      hemilaryngectomy. Four patients had recurrence of disease. Two patients with
      recurrence required radiation therapy and 2 patients required a total
      laryngectomy. With the selective application of multiple endoscopic excisions,
      radiation therapy, and more invasive operation, 100% of patients are without
      evidence of disease with a laryngeal preservation rate of 96%. CONCLUSIONS: This
      study supports the use of endoscopic excisional biopsy as the primary treatment
      modality for lesions ranging from carcinoma in situ to invasive T1 glottic
      carcinoma. This study also highlights the importance of close clinical follow-up
      and the potential need for further treatment. By reserving open operation and
      radiation therapy to selective cases, we successfully treated all patients while
      limiting the disadvantages of radiation therapy and more invasive operation to
      the minority of patients.

PMID- 11997774
TI  - Can patient satisfaction with decisions predict compliance with surgery?
AB  - BACKGROUND: Patient satisfaction with treatment decisions is a discrete and
      measurable component of the satisfaction paradigm, distinct from satisfaction
      with health care services. OBJECTIVE: The study goal was to determine if the
      Satisfaction With Decision (SWD) scale, a valid and reliable 6-item survey, can
      predict patient compliance with surgery proposed by their otolaryngologist.
      DESIGN: Prospective study using the SWD scale plus measures of office visit
      satisfaction, provider satisfaction, and disease-specific quality of life.
      SETTING: Metropolitan, private nonprofit hospital. PATIENTS: The study population
      consisted of 151 patients scheduled for surgery, with a median age of 5.8 years
      and an age range of 0.6 to 65.3 years. INTERVENTIONS: At the time surgery was
      scheduled, the decision-maker completed a 12-item questionnaire about
      satisfaction and quality of life that included the SWD scale. Noncompliant
      patients were contacted, and the specific reason for cancellation was
      ascertained. RESULTS: The strongest predictor of surgical cancellation was the
      SWD survey score, with a median value of 4.8 for patients completing surgery
      compared with 3.8 for those who cancelled (P < 0.001). Patients with scores <4.0
      had a 57% cancellation rate, whereas those with scores > or =4.0 had a 98%
      completion rate. Patients were also more likely to cancel if it was their first
      visit with the surgeon (P = 0.004) or if they were responsible for their own
      decisions (P = 0.007). Cancellations were not associated with office visit
      satisfaction, patient quality of life, or demographic characteristics of the
      decision-maker. CONCLUSIONS: Patients who are satisfied with their initial
      decision to undergo surgery are most likely to comply with planned therapy.
      Conversely, patients who score <4.0 on the SWD scale may benefit from additional
      preoperative counseling to increase the likelihood of compliance.

PMID- 11997775
TI  - Evidence-based medicine in otolaryngology journals.
AB  - OBJECTIVE: We set out to assess, within the context of evidence-based medicine,
      the levels of supporting evidence for therapeutic recommendations made in leading
      otolaryngology journals. DESIGN: We used a cross-sectional survey of clinical
      research articles published in 1999 in 4 high-circulation otolaryngology
      journals. OUTCOME MEASURES: We used study design methodology and level of
      evidence for clinical research articles with therapeutic recommendations.
      Outcomes were stratified by type of recommendation (positive vs negative) and by
      study focus (medical vs surgical therapy). RESULTS: Of the 1019 articles
      identified, 737 (72%) were clinical research and 268 (36%) made therapeutic
      recommendations. Median sample size was modest (27 subjects), with only 38% of
      studies reflecting planned research and 22% including an internal control or
      comparison group. Positive studies were 20 times more prevalent than negative
      ones, but were 69% less likely to have an internal control group (P =.042) and
      93% less likely to include confidence intervals (P =.020). Moreover, the level of
      evidence for positive studies was lower than for negative studies (P =.037), with
      twice as many negative recommendations supported by analytic research. Similarly,
      the level of evidence for operation was lower than for medical therapy (P <.001),
      with 3 times as many medical recommendations supported by analytic research.
      CONCLUSIONS: Most therapeutic recommendations in otolaryngology journals are on
      the basis of descriptive case series (80%) and least often on randomized
      controlled trials (7%). A dual standard appears to exist for negative versus
      positive studies and for medical versus surgical recommendations. Greater
      scrutiny of the breadth and quality of evidence levels supporting therapeutic
      recommendations is likely to occur as the popularity of-and demand for-evidence
      based medicine increases. SIGNIFICANCE: Evaluation of levels of evidence in
      otolaryngology decision making.

PMID- 11997776
TI  - Middle meatal vs antral lavage cultures in intensive care unit patients.
AB  - OBJECTIVE: The study goal was to compare endoscopically guided middle meatal
      cultures with cultures of antral lavage aspirate in intensive care unit (ICU)
      patients with sinusitis. METHODS: Prospective study of febrile ICU patients seen
      for sinusitis at a tertiary medical center. RESULTS: Of 31 antral lavages
      performed in 18 patients, 19 lavages yielded purulent or mucopurulent aspirate.
      Endoscopically guided middle meatal cultures yielded the same pathogen, as did
      cultures of the lavage aspirate in 4 (21%) of these 19 cases. The antral lavage
      was negative (absence of purulent/mucopurulent aspirate) in 12 cases, and of
      those, 5 (42%) of the 12 middle meatal cultures showed no growth (sensitivity =
      21%, specificity = 58%, chi(2)-1.52, P = 0.218). CONCLUSION: Endoscopically
      guided middle meatal cultures did not correlate well with cultures from the
      antral lavage aspirate in febrile ICU patients evaluated for sinusitis.

PMID- 11997777
TI  - Autonomic dysfunction, vasomotor rhinitis, and extraesophageal manifestations of
      gastroesophageal reflux.
AB  - OBJECTIVE: Several recent reports suggest there may be a relationship between
      chronic rhinitis and extraesophageal manifestations of gastroesophageal reflux
      (EER). It is hypothesized that this relationship is a result of autonomic nervous
      system (ANS) dysfunction. STUDY DESIGN: Patients with isolated vasomotor rhinitis
      (VR), both VR and EER, and a control group were studied by a battery of tests
      designed to objectively evaluate ANS function. In addition all 3 groups underwent
      barium esophagogram and 4-site (proximal pharynx, distal pharynx, proximal
      esophagus, and distal esophagus) ambulatory pH monitoring. Adult patients
      fulfilling diagnostic criteria for VR, and with both VR and EER underwent
      objective ANS testing in a recently developed ANS testing laboratory. The control
      group consisted of age- and sex-matched adults without diagnostic criteria for VR
      or EER. RESULTS: In patients with VR only (n = 9), 2 patients had a positive
      esophagogram, whereas a positive pharyngeal reflux probe was found in 1 and an
      abnormal composite autonomic scoring scale (CASS) was found in 8 (mean VR CASS =
      1.750 vs control CASS 0.556, P =.02). The group with VR and EER (n = 12) had a
      positive esophagogram in 10 patients, positive pharyngeal reflux by probe in 9,
      and all 12 had an abnormal CASS (mean CASS VR/EER = 2.909 vs CASS control =
      0.556, P =.001 and vs VR CASS = 1.750, P =.05). The control patients (n = 9) had
      normal transesophageal gastroduodenoscopy in 8, 1 had a positive pharyngeal probe
      study, and all 9 had a normal CASS. In addition ANS testing in patients with
      diagnostic criteria for both VR/EER revealed statistically significant evidence
      of an adrenergic deficit as compared with control patients on the basis of mean
      phase II blood pressure response to Valsalva maneuver (mean phase II VR/EER = 
      16.730 vs control = -7.780, P =.05). In the VR only group, the phase II blood
      pressure decrease was greater than in control patients, but did not reach
      statistical significance (mean phase II VR = -9.370 vs control = -7.780, P =
      0.672). CONCLUSION: Patients with VR and VR/EER have objective evidence of ANS
      dysfunction when compared with a group of age- and sex-matched control patients.
      Patients with both VR/EER demonstrate a significantly greater degree of ANS
      dysfunction than patients with isolated VR. The mechanism by which VR and EER
      interact is not entirely clear, but ANS dysfunction is objectively associated
      with both disorders. In addition, patients with VR/EER seem to demonstrate
      hypofunction of the adrenergic component of the ANS, in contrast to the generally
      held hypothesis that VR results from increased cholinergic activity. Further
      characterization of the type of ANS abnormality may allow the development of
      novel pharmacologic therapies for these disorders.

PMID- 11997778
TI  - Effectiveness of second-generation fibrin glue in endonasal operations.
AB  - We evaluated the efficacy and safety of the Quixil fibrin sealant after its
      application to endonasal operative sites. A total of 153 patients underwent nasal
      surgery. The rate of hemorrhagic complications was compared in the group with
      nasal packing and in the group in whom fibrin glue was used to stop postoperative
      bleeding. Our results indicate that the application of Quixil fibrin glue to the
      operative sites in various endonasal operations provides effective hemostasis and
      sealing. This fibrin glue is a more effective hemostatic agent than foam nasal
      packing and provides no complications, as can occur with packing. Patients with
      hypertension have no greater risk for postoperative bleeding if Quixil is used.

PMID- 11997779
TI  - Role of the tongue base suspension suture with The Repose System bone screw in
      the multilevel surgical management of obstructive sleep apnea.
AB  - OBJECTIVE: The Repose System (tongue base suspension) is a new, minimally
      invasive technique for tongue base suspension in the treatment of obstructive
      sleep apnea. The purpose of this project was to describe our preliminary
      experience using this tongue base suspension system in conjunction with
      uvulopalatopharyngoplasty (UPPP) in the multilevel surgical approach to the
      management of obstructive sleep apnea (OSA). STUDY DESIGN: We conducted a
      retrospective analysis of 19 consecutive patients undergoing UPPP and The Repose
      System tongue base suspension for the management of obstructive sleep apnea
      during a 1-year period (1998 through 1999). RESULTS: Fifteen patients (11 men and
      4 women) had complete preoperative and postoperative polysomnographic data. A 46%
      reduction in the preoperative respiratory disturbance index (RDI) (38.7 +/- 12.3)
      versus the postoperative RDI (21.0 +/- 7.4, P < 0.05) was demonstrated at a mean
      of 3.8 months after surgery. The apnea index demonstrated a 39% reduction. The
      surgical cure rate was 20% (3 of 15 patients). CONCLUSIONS: The Repose System in
      conjunction with UPPP has been shown to produce significant reductions in the RDI
      and apnea index as well as a significant increase in O2 saturation. Despite the
      improvement in these objective parameters, the overall surgical cure rate was
      only 20% (3 of 15 patients) in this retrospective series. Further research is
      warranted to define the role of The Repose System in the management of
      obstructive sleep apnea patients with multilevel airway obstruction.

PMID- 11997780
TI  - Same-stage nasal and palatopharyngeal surgery for obstructive sleep apnea: is it
      safe?
AB  - OBJECTIVE: The study goal was to determine the safety of performing same-stage
      nasal and palatopharyngeal surgery for the treatment of obstructive sleep apnea
      syndrome (OSAS). STUDY DESIGN AND SETTING: We conducted a retrospective review of
      91 consecutive patients who underwent surgery for OSAS at tertiary care
      facilities. METHODS: Patients were divided into 2 groups: group 1 had same-stage
      nasal and palatopharyngeal surgery (n = 63), whereas group 2 had palatopharyngeal
      surgery at a stage separate from the nasal surgery (n = 28). Patient
      demographics, severity of OSAS, type of surgery, perioperative care, and
      postoperative complications were reviewed. RESULTS: There were 55 men and 8 women
      in group 1, with an average age of 48 years. Group 2 consisted of 20 men and 8
      women, with an average age of 45 years. The mean respiratory disturbance index
      was 36.5 and 33.5 for group 1 and 2, respectively. The mean lowest arterial
      Oxygen saturation for group 1 was 82%, whereas that of group 2 was 81%. Patients
      in both groups were observed in a hospital setting for a minimum of 1 day. They
      were admitted to a room close to the nurse's station, with continuous pulse
      oximeter monitoring. There were 3 complications reported for group 1: pneumonia
      (1 patient, postoperative day 4), tonsil bleed (1 patient, postoperative day 6),
      and septal hematoma (1 patient). One patient in group 2 had a tonsil bleed
      (postoperative day 8). There were no incidents of airway compromise or
      cardiopulmonary events in the immediate postoperative period. CONCLUSION: Same
      stage nasal and palatopharyngeal surgery for OSAS is safe. Patients could be
      monitored with continuous pulse oximetry and managed outside of an intensive care
      unit setting in the immediate postoperative period.

PMID- 11997781
TI  - Inhibition of matrix metalloproteinases in gerbil cholesteatoma: preliminary
      findings.
AB  - OBJECTIVES: This study was conducted to examine the role of matrix
      metalloproteinases (MMPs) and the impact of a topical MMP inhibitor, ilomostat,
      on the development of tympanic membrane (TM) atelectasis in the gerbil model.
      METHODS: Eustachian tubes were cauterized bilaterally in 19 gerbils. Thereafter,
      both TMs received once-daily topical treatment for 8 weeks with ilomostat or
      vehicle or no treatment (n = 6 or 7 per group). TM atelectasis was serially
      graded, and TMs were harvested at 8 weeks. Gelatin zymograms were performed to
      determine MMP activity. RESULTS: The mean activity levels of proenzyme and active
      MMP-9 and MMP-2 and degree of atelectasis did not differ between groups. TM
      atelectasis did not correlate to levels of enzymes across individual samples.
      CONCLUSIONS: Topical application of an MMP inhibitor did not significantly
      prevent the development of TM atelectasis. It remains to be determined whether
      the use of MMP inhibitors may prevent the progression of atelectasis in humans.

PMID- 11997782
TI  - Congenital cholesteatoma: 20 years' experience at The Children's Hospital of
      Philadelphia.
AB  - OBJECTIVE: We report our experience with congenital cholesteatoma over a span of
      20 years with an emphasis on presenting characteristics and predictors of
      outcome. METHODS: We conducted a retrospective review from 1981 through 2000.
      RESULTS: One hundred seventy-two congenital cases were identified in 167
      patients. Five patients had bilateral disease. The majority (72%) were found in
      boys, with an average age of 5.0 years. Hearing loss was slight to moderate. When
      confined to 1 quadrant, cholesteatoma was anterosuperior in 82% of cases; 47% had
      cholesteatoma in 2 or more quadrants. Ossicular chain involvement was found in
      43% of all cases, and mastoid extension was evident in 23%. The rate of recurrent
      disease was directly related to the extent and number of quadrants involved.
      CONCLUSION: To our knowledge, this is the largest series of congenital
      cholesteatomas to be reported. This review confirms the male predominance and
      predilection for the anterosuperior quadrant. The extent of cholesteatoma and its
      relation to residual disease should be used as a guide for planning a second-look
      procedure.

PMID- 11997783
TI  - No evidence of acute Chlamydia pneumoniae infection in patients with Bell's
      palsy.
AB  - The cause of Bell's palsy remains unknown even though available evidence suggests
      that infection could be a factor. In recent studies, Chlamydia pneumoniae has
      been associated with neurologic diseases such as multiple sclerosis. In the
      present study, the association of C pneumoniae with Bell's palsy was studied with
      the use of serology and polymerase chain reaction to test tear fluid and
      peripheral blood mononuclear cells from 21 patients with Bell's palsy and 21
      control subjects. C pneumoniae DNA was detected from tear fluid samples in 1
      patient with Bell's palsy and in 2 healthy control subjects. Whether this
      indicates earlier disease or subclinical infection remains to be studied.
      However, an association between Bell's palsy and acute C pneumoniae infection
      could not be shown.

PMID- 11997784
TI  - Tumor necrosis factor-alpha and interleukin-1beta levels in recurrent and
      persistent otitis media with effusion.
AB  - OBJECTIVE: Based on interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha
      levels in effusions, our goals were to specify either recurrent or persistent
      otitis media with effusion (OME) is a mid stage in the development of chronic
      disease and to identify the factors that have an influence on cytokine levels.
      STUDY DESIGN: Samples from groups with recurrent (n = 15) and persistent (n = 39)
      OME were assayed for IL-1beta and TNF-alpha. Children were also grouped with
      respect to age, sex, quality of effusion, and the presence of pharyngeal adenoid
      tissue. SETTING: Tertiary referral center. RESULTS: In recurrent and persistent
      OME groups, IL-1beta was higher than TNF-alpha (P < 0.01). IL-beta was higher in
      recurrent OME than in persistent OME (P < 0.05). CONCLUSION: Recurrent OME seems
      to be closer to the chronic stage of the disease relative to persistent OME in
      terms of higher IL-1beta levels. Each exacerbation of acute disease in recurrent
      otitis media is likely to be mediated by IL-1beta. SIGNIFICANCE: We were able to
      clarify that recurrent OME is a stage that occurs before chronic OME. Therefore,
      the prevention of acute attacks in recurrent disease would also impede long-term
      damage to the middle ear.

PMID- 11997785
TI  - Synchronous ipsilateral cerebellopontine angle glossopharyngeal schwannoma and
      parotid adenoid cystic carcinoma.

PMID- 11997786
TI  - Xanthoma of the maxillary sinus.

PMID- 11997787
TI  - Synovial sarcoma of the pericricoidal soft tissue.

PMID- 11997788
TI  - Pleomorphic lipoma of the tongue.

PMID- 11997789
TI  - Management of advanced adenocarcinoma of maxillary sinus in a young woman during
      pregnancy: a case report.

PMID- 11997790
TI  - Unusual metastasis to the mandibular alveolus of a malignant pleural
      mesothelioma.

PMID- 11997791
TI  - Unrecognized aspiration of a dental retainer: a case report.

PMID- 11997792
TI  - Oncocytoma of the nasal septum: a rare cause of epistaxis.

PMID- 11997793
TI  - Mucocele of the middle turbinate: a case report.

PMID- 11997794
TI  - Multifocal malignant paraganglioma of the paranasal sinuses: a case report.

PMID- 11997795
TI  - Tuberculosis tonsillitis.

PMID- 11997796
TI  - Colloid cyst of third ventricle: a rare cause of episodic vertigo.

PMID- 11997797
TI  - Localized cryptococcal infection combined with cholesteatoma of the ear.

PMID- 11997798
TI  - Cervicocutaneous sarcoidosis.

PMID- 11997799
TI  - The future of screening for retinopathy of prematurity.

PMID- 11997800
TI  - Telephotoscreening to detect retinopathy of prematurity: preliminary study of the
      optimum time to employ digital fundus camera imaging to detect ROP.
AB  - PURPOSE: Labor-intensive screening of infants in the neonatal intensive care
      units is the only way presently to detect retinopathy of prematurity (ROP). Our
      purpose is to determine if RetCam 120 images (Massie Research Laboratories, Inc,
      Dublin, Calif), acquired by a neonatal nurse, can be used to screen for ROP by
      performing 2 screening sessions, at 32 to 34 weeks' (examination 1) and 38 to 40
      weeks' (examination 2) postconceptional age. METHODS: RetCam examinations were
      performed by a nurse on infants at examination 1 and examination 2 intervals. At
      the same time, an examination was performed by an experienced ophthalmologist.
      Masked readers evaluated the digital images for the presence of ROP and, if ROP
      was present, estimated the risk of that eye progressing to prethreshold or
      threshold disease. The data were compared to the eye's clinical course. RESULTS:
      A total of 46 eyes were assessed at examination 1 and 50 eyes at examination 2
      from July 1, 1999, to December 15, 1999. For detecting ROP, the sensitivity and
      specificity were 46% and 100% for examination 1 and 76% and 100% for examination
      2. Sensitivity and specificity of predicting prethreshold was 64% and 97%,
      respectively, for examination 1 and 2. Sensitivity for predicting ROP threshold
      at examination 1 was 0% (only 1 photo was available for grading of sensitivity)
      and specificity for predicting ROP threshold at examination 1 was 95%. At
      examination 2, sensitivity and specificity were 100%. CONCLUSION: The RetCam
      examination had insufficient sensitivity to be recommended as a substitute for
      indirect ophthalmoscopy in screening for ROP. Reasons for low sensitivity are the
      technical limitation of the camera design itself, which creates difficulty in
      photographing the peripheral retina in small eyes, and the need for a lid
      speculum better adapted to the contact camera optical system design. Both of
      these issues are being addressed as part of an ongoing project to study the
      feasibility of employing telemetry of digital fundus images from remote,
      underserved neonatal intensive care units to ophthalmologists capable of
      diagnosing ROP.

PMID- 11997801
TI  - Radiotherapy in thyroid eye disease: the effect on the field of binocular single
      vision.
AB  - PURPOSE: Thyroid eye disease (TED) can be a functionally disabling condition if
      ocular muscle involvement causes diplopia. The extraocular muscle restriction
      creates a reduced or eccentric field of binocular single vision (BSV). Orbital
      radiotherapy is now widely used in the treatment of TED, and although it has been
      reported as improving ocular motility, there have been few quantitative studies
      of the effect of treatment on ocular motor function. METHODS: Retrospective case
      note review of patients undergoing orbital radiotherapy for TED between 1992-1998
      identified 79 case records. A total of 27 patients had diplopia in primary
      position or a significantly reduced binocular field before undergoing
      radiotherapy. The fields of BSV were analyzed pretreatment and at 3, 12, and 24
      months after therapy to assess any improvement in function. We used the field of
      BSV as an outcome measure because it can be quantified and is a good indicator of
      functional ability. RESULTS: None of the 12 patients with double vision in
      primary position pretreatment regained a central binocular field with
      radiotherapy alone. Of the 15 patients with a central but reduced binocular
      field, 8 (53%) remained unchanged with treatment. In 4 patients (26.6%), there
      was an improvement in the field, while in 3 (20%) the field deteriorated. In all,
      12 patients (44%) went on to require strabismus surgery. CONCLUSIONS: Orbital
      radiotherapy alone is ineffective in treating restrictive thyroid myopathy and
      improving binocular function.

PMID- 11997802
TI  - Surgical results in large-angle exotropia.
AB  - PURPOSE: This study examines the surgical results of correcting large angle
      exodeviations in adults who may lack bifixation. The expected results in adults
      are not to achieve improved fusion but, rather, to construct the alignment.
      METHODS: A retrospective chart review was conducted of all patients with comitant
      exodeviation greater than 35 Delta examined and treated by 1 pediatric
      ophthalmologist between January 1994 and May 1999. Any patients with large A or V
      patterns, nystagmus, history of botulinum toxin injections for strabismus,
      paralytic or mechanical cause for strabismus, or use of adjustable sutures were
      excluded. Charts were reviewed for postoperative alignment. Postoperative results
      were separated into 3 categories: exodeviation greater than 10 Delta, successful
      outcome (esotropia<10 Delta, orthotropia, or exodeviation <10 Delta), or
      esotropia greater than 10 Delta. RESULTS: Sixty-three patients met the inclusion
      criteria. Their median age at the time of surgery was 18, with a standard
      deviation of 20. The majority of them had intermittent exotropia that had
      deteriorated into constant exotropia. Fifty-two patients had bilateral lateral
      rectus recessions, and 11 patients had recess/resect procedures. Sixty-two
      percent (39 of 63) had successful outcomes overall. Only 2 patients had
      overcorrection (esotropia>10 Delta). In patients with deviations greater than 50
      Delta, 82% (9 of 11) were undercorrected (exodeviation >10 Delta). CONCLUSIONS:
      Large-angle exodeviations can be successfully approached with bilateral lateral
      rectus recessions or recess/resect procedures in preoperative deviations up to
      and including 50 Delta with a success rate of 71%. In larger deviations, 2-muscle
      surgery was not as successful (18%, or 2 of 11).

PMID- 11997803
TI  - Clinical outcome of confluent laser photoablation for retinopathy of prematurity.
AB  - PURPOSE: During the past decade, laser photoablation has supplanted cryotherapy
      as the standard treatment for threshold retinopathy of prematurity (ROP). We
      evaluated the progression and the complication rate in a cohort of infants with
      threshold ROP treated with a confluent technique. METHODS: We retrospectively
      studied 47 patients with ROP (91 eyes), treated with confluent diode laser
      photoablation. Four main outcomes were evaluated: (1) the rate of progression,
      (2) the frequency of laser retreatment, (3) postoperative complications, and (4)
      postoperative refractive error. RESULTS: A mean of 1943 +/- 912 laser burns were
      administered in a confluent pattern to 91 eyes with threshold ROP. Progression to
      stage 4 or 5 disease occurred in 13 of 29 eyes (44.8%) with zone I and posterior
      zone II and in 2 of 51 eyes (3.9%) with anterior zone II ROP (P =.01). Eyes with
      anterior zone II ROP that received more than or equal to 2000 burns progressed
      more than those that received fewer than 2000 burns. Only 1 eye (1%) needed a
      supplemental laser treatment. Postoperative complications included corneal edema
      (2.3%), anterior segment ischemia (2.3%), vitreous hemorrhage (7.9%), posterior
      synechiae (2.3%), cataract (4.9%), and macular ectopia (12%). The mean spherical
      equivalent at the last follow-up was -4.52 +/- 5.63 D. CONCLUSIONS: In our
      series, infants received more laser burns than infants reported in the literature
      receiving scatter or near-confluent treatment. While confluent treatment almost
      eliminated supplemental treatment, it was associated with a similar rate of
      progression and complications as has been reported with other patterns of laser
      treatment.

PMID- 11997804
TI  - Sensitivity of photoscreening to detect high-magnitude amblyogenic factors.
AB  - PURPOSE: To determine the sensitivity of a unique pupil-size based set of
      referral criteria of the MTI PhotoScreener(Medical Technology and Innovations,
      Inc, Cedar Falls, Iowa) to detect high magnitude refractive error. METHODS: The
      photoscreening photographs of 949 preschool children previously analyzed were
      reevaluated with the new referral criteria. The original photographs had been
      obtained from pediatricians' offices and public health and Women, Infants, and
      Children's (WIC) clinics. The results of this analysis were compared with the
      gold standard clinical examination and cycloplegic refraction. Sensitivities were
      calculated for amblyogenic factors based on the magnitude of the refractive
      error. RESULTS: For 26 patients with anisometropia, the sensitivity to detect
      anisometropia increased from 46% for +1.25 or greater spherical interocular
      difference to 100% for +2.50 spherical intraocular difference. For 36 patients
      with hypermetropia in at least 1 meridian ranging from +3.75 to +7.50 D,
      sensitivity increased from 53% to detect +3.75 D or greater to 70% for +5.00 D or
      greater. The sensitivity to detect hypermetropia of +5.75 D or greater was 100%.
      These criteria detected 82% of patients with astigmatism greater than or equal to
      +3.00 D, and 100% of patients with astigmatism greater than +3.50 D. CONCLUSION:
      It is crucial that screening programs avoid over-referrals caused by high false
      positive screening rates. The sensitivity of our new criteria increases with
      higher magnitude refractive error; patients with moderate and severe amblyogenic
      factors are almost never missed. While the sensitivity to detect lower magnitude
      refractive error is poor, the amblyogenic impact of such errors remains to be
      determined.

PMID- 11997805
TI  - Unilateral persistent hyperplastic primary vitreous: course and outcome.
AB  - PURPOSE: Improved surgical techniques enable more favorable results in the
      management of persistent hyperplastic primary vitreous (PHPV). The purpose of our
      study was to evaluate the outcome of PHPV eyes managed conservatively or after
      surgery (with or without intraocular lens implantation). METHODS: A total of 89
      children (37 boys, 52 girls) with PHPV in one eye (mean follow-up of 6.3 +/- 5.7
      years) were included. The children were subgrouped according to treatment
      modality. Twenty-eight (31.5%) children were managed conservatively
      (nonoperated). Cataract extraction combined with vitrectomy and removal of
      embryonic remnants was carried out in 61 eyes (68.5%). Intraocular lenses were
      implanted in 30 of the operated eyes (pseudophakic) and 31 eyes remained without
      lens (aphakic). RESULTS: Final evaluated visual acuity in the entire group was
      6/15 or better in 12.6% (11 of 87) of the eyes. A total of 11.5% (10 of 87) had a
      visual acuity of 6/21 to 6/60, 46.0% (40 of 87) obtained 6/90 to light perception
      and 26 of 87 (29.9%) had no light perception in the involved eye. The rate of no
      light perception was significantly lower in patients with pseudophakia (10.0%)
      compared to those with aphakia (43.3%) or nonoperated (37.0%) eyes (P =.009).
      Intraocular pressure was adequately assessed repeatedly in 72 eyes. High
      intraocular pressure and glaucomatous changes were observed in 7 of 31 (22.6%)
      patients with aphakia, 2 of 24(8.3%) patients with pseudophakia and in 2 of
      17(11.8%) nonoperated eyes (P =.34). Poor cosmetic outcome was seen in 12 of 31
      (38.7%) children with aphakic eyes and 5 of 30 (16.7%) children with pseudophakic
      eyes (P =.08). Prosthesis or cosmetic shells were needed for 8 of 31 patients
      with aphakia, for none of the patients with pseudophakia and for 2 of 28 of the
      nonoperated children (P =.003). CONCLUSION: PHPV eyes have a potential for
      developing useful vision with favorable cosmetic outcome after surgery.
      Intraocular lens implantation may be a favorable and beneficial option for the
      management of children with unilateral PHPV.

PMID- 11997806
TI  - Effects of extraocular muscle tenotomy on congenital nystagmus in macaque
      monkeys.
AB  - INTRODUCTION: Extraocular muscle tenotomy has been reported to damp congenital
      nystagmus in an achiasmatic sheepdog. We performed extraocular muscle tenotomy to
      evaluate its effects on congenital nystagmus in primates. METHODS: Magnetic
      search coil eye movement recordings were used to document the presence of
      horizontal congenital nystagmus in 2 adult macaque monkeys that also had
      naturally occurring infantile strabismus. Extraocular muscle tenotomy was
      performed by operating on all 4 horizontal recti, surgically detaching the
      muscles from the globe and suturing them back to their original insertions
      without resection or recession. Eye movement recordings were repeated 4 months
      after the procedure, comparing the waveform, amplitude, retinal slip velocity,
      and intensity (frequency x amplitude) of the nystagmus before and after tenotomy.
      Visual acuity was also measured before and after surgery in 1 animal. RESULTS:
      Preoperatively, a disconjugate, pendular nystagmus was evident in 1 monkey, and
      the other had a conjugate pendular-jerk nystagmus damped by convergence. After
      tenotomy, nystagmus mean amplitude decreased 18% to 52% in 1 monkey but increased
      14% in the other (t test, P <.002). Retinal slip velocity and nystagmus intensity
      increased in both monkeys. After tenotomy, mean velocity increased 22% to 218%,
      while mean intensity increased 40% to 208% (t test, P <.002). Visual acuity
      measured after tenotomy decreased an average of 20% ( approximately 2.0 cycles
      per degree) in each eye. Tenotomy had no noteworthy effects on eye alignment or
      other aspects of visual behavior other than the congenital nystagmus. CONCLUSION:
      Nystagmus velocity and intensity increased after extraocular muscle tenotomy in 2
      monkeys. Further studies are required to establish the clinical value of this
      procedure as a treatment for various subtypes of congenital nystagmus in humans.

PMID- 11997807
TI  - Functional results after treatment of retinoblastoma.
AB  - PURPOSE: Because of the long-term complications associated with external beam
      radiation in retinoblastoma, alternative treatment methods have been
      investigated. We conducted a retrospective study to evaluate the functional
      results of new treatment modalities. METHODS: Thirty-seven eyes were treated
      without external beam irradiation in 31 patients. The median diameter of the
      largest tumor in each eye was 6 mm. Primary chemotherapy was used in 25 cases,
      chemothermotherapy was used in 32 cases, cryotherapy was used in 28 cases, iodine
      125 Plaques were used in 15 cases, diode laser thermotherapy was used alone in 11
      cases, and photocoagulation was performed in 5 cases. The median follow-up after
      diagnosis of retinoblastoma was 41 months. The visual results were evaluated at a
      median age of 54 months. RESULTS: The median visual acuity of the treated eyes
      was 20/33. Twenty-four eyes presented a visual acuity better than 20/40, 4 eyes
      had a visual acuity between 20/200 and 20/40, and 9 eyes had a visual acuity less
      than 20/200. Maculopathy was observed in 16 cases, associated with papillopathy
      in 1 case. A cataract was observed in 1 case and a vitreous hemorrhage was
      observed in another case. Twenty-one eyes did not develop any complications. No
      corneal dryness and very few lens changes were observed. CONCLUSION: The
      functional results after local treatments for retinoblastoma are very good. The
      most frequent complication is maculopathy, particularly when the tumor involves
      or is situated close to the macula.

PMID- 11997808
TI  - A new dose-response curve for bilateral medial rectus recessions for infantile
      esotropia.
AB  - PURPOSE: In 1982, Mims et al generated the first rigorous dose-response curve for
      bilateral medial rectus recessions for infantile esotropia (ET). Curve fitting
      calculations were hampered by substantial variability of surgical effect for the
      larger angles of ET, and an exponential curve was chosen for angles below 30 ET
      and a straight line for angles above 30 ET. In a continuing effort to improve the
      surgical success rate, a new series of results of 113 bilateral medial rectus
      recessions performed from 1990 to 1998 for infantile ET has been analyzed to
      produce a new dose-response curve and to study other potentially useful
      variables. METHODS: The amount of medial rectus recession performed in this
      series was the original dose-response curve from 1982, with conjunctival
      recessions performed for angles above 35 ET. RESULTS: The best curve that could
      be fitted to the effect versus millimeters of bilateral medial rectus recession
      was a single exponential curve. Other parameters explored with multivariate
      analysis, including head circumference, developmental delay, and intraoperative
      angles under anesthesia were not helpful in predicting effect of surgery at 6
      weeks postoperative. A total of 87% were aligned at 6 months after surgery.
      Surgical failure at 6 months was more prevalent with larger preoperative angles
      (P =.0007) and with developmental delay (age when child first sat alone; P
      =.0078). CONCLUSION: Between 1982 and 1990, decreased variability of results of
      bilateral medial rectus recessions for larger angles of infantile ET enabled the
      generation of a single exponential dose-response curve for the entire range of
      angles of infantile ET.

PMID- 11997809
TI  - Cystoid macular edema following extraocular muscle surgery.

PMID- 11997810
TI  - Delayed endophthalmitis in a child following an Ahmed glaucoma valve implant.

PMID- 11997811
TI  - Hemifacial atrophy (Parry-Romberg syndrome, #141300) with papillitis, retinal
      alterations, and restriction of motility.

PMID- 11997812
TI  - What the Distribution of Cell Lengths in the Root Meristem Does and Does Not
      Reveal About Cell Division.
AB  - Roots have long been realized to be useful material for studies of cell division.
      Despite this long history of use, the behavior of cells in the meristem is often
      misinterpreted. A common error is to argue that differences in cell length
      reflect differences in cell division rate. In this article we explain the fallacy
      behind this argument and show how the analysis of cell length distribution can
      lead to insight about the root meristem. These observations support a model for
      the root meristem where cells of various tissues grow at the same relative growth
      rate and divide at the same frequency, indicating that these growth parameters
      are built into the cells at a fundamental level. The differences in cell length
      between various tissues appear to arise at their formation, first at the tissue
      initials and ultimately in the seed. Length differences among mature cells may be
      enhanced by differences in the location within the meristem where division
      ceases. Discovering mechanisms regulating the length of initial cells and the
      position where cells cease division requires a realistic understanding of how
      growth constrains the division behavior of dividing cells.

PMID- 11997813
TI  - Evidence-based medicine: open and laparoscopic bariatric surgery.
AB  - BACKGROUND: The aim of this study was to perform an evidence-based analysis of
      the literature on open and laparoscopic surgery for morbid obesity. METHODS:
      Human studies on surgery for morbid obesity were conducted. Multiple publications
      of the same studies, abstracts, and case reports were reviewed. Current Contents,
      MEDLINE, EMBASE, and Cochrane Library databases were investigated. RESULTS: Open
      Roux-en-Y gastric by pass (RYGB) for morbidly obese patients and long-limb RYGB
      for superobese patients are highly effective procedures. Randomized controlled
      trials comparing malabsorptive procedures with other bariatric operations are
      needed. The long-term efficacy of adjustable silicone gastric banding (ASGB)
      still is undetermined because of poor evidence. Laparoscopic RYGB is as safe as
      its open counterpart, although its long-term results are lacking. Laparoscopic
      ASGB is less invasive than open ASGB, although its efficacy cannot be determined
      because of poor evidence. Laparoscopic vertical banded gastroplasty (VBG) is
      becoming unpopular since the decreasing trend of open VBG. Laparoscopic
      biliopancreatic diversion with duodenal switch is feasible, but needs further
      studies. CONCLUSIONS: Randomized controlled trials comparing the various
      laparoscopic operations are strongly needed.

PMID- 11997814
TI  - Long-term outcome of laparoscopic repair of paraesophageal hernia.
AB  - BACKGROUND: It has been reported that the laparoscopic repair of paraesophageal
      hernias is associated with higher complication and recurrence rates than the open
      methods of repair. METHODS: We identified 136 consecutive patients who underwent
      laparoscopic repair of a paraesophageal hernia between 1993 and 1999. Patient
      demographics and symptom scores for regurgitation, heartburn, chest pain, and
      dysphagia at presentation and at last follow-up were recorded (0 = none, 1 =
      mild, 2 = moderate, 3 = severe). The operative records were reviewed, and early
      and late complications were noted. Only patients with a follow-up of >1 were
      included in the analysis. RESULTS: The median age was 64 years, and there was a
      female preponderance (1.8:1). Most patients had some medical comorbidity; the
      American Society of Anesthesiologists (ASA) scores were <2 in eight patients and
      ?2 in 117 patients. Three laparoscopic operations were converted to open
      procedures. There were nine intraoperative complications, five early
      complications, and three related deaths (morbidity and mortality rates of 10.2%
      and 2.2%, respectively). Follow-up data were available for 83 patients (66%), and
      the mean follow-up time was 40 months (range, 12-82). The percentage of patients
      experiencing chest pain, dysphagia, heartburn, and regurgitation in the moderate
      to severe range dropped from a range of 34-47% to 5-7% (p <0.05). Three patients
      underwent repeat laparoscopic repair for symptomatic recurrence. CONCLUSION: The
      laparoscopic repair of paraesophageal hernias provides excellent long-term
      symptomatic relief in the majority of patients and has a low rate of symptomatic
      recurrence. The complication and death rates may be related in part to the higher
      incidence of comorbidities in this somewhat elderly patient population.

PMID- 11997815
TI  - Laparoscopic vs open approach for the treatment of gastroesophageal reflux in
      children.
AB  - BACKGROUND: The laparoscopic approach has become increasingly popular for
      fundoplication over the last few years; however many surgeons are skeptical about
      its real advantages. METHODS: We conducted a prospective comparative study of
      children operated on for gastroesophageal reflux (GER). Exclusion criteria
      included age <1 YEAR AND >14 years, previous surgery on the esophagus or stomach,
      and neurologic impairment. We compared two groups of patients who met the same
      inclusion/exclusion criteria. One group was treated via a laparotomic approach
      between January 1993 and December 1997; the other was treated via a laparoscopic
      approach between September 1998 and December 2000. A 360 degrees wrap was
      performed in each group. RESULTS: Group 1 (laparotomic approach) included 17
      patients; mean operative time was 100 min and postoperative time was 7 days.
      Group 2 comprised 49 children operated on via a laparoscopic approach; mean
      operative time was 78 min and postoperative time was 48 hours. No major
      complications were encountered in either group. In postoperative period, two
      patients in group 1 had complications. One had a prolonged bout of gastroplegia,
      which required nasogastric drainage, and then recovered spontaneously after 20
      days; the other had stenosis of the wrap, which required dilation. No relapses
      occurred during a follow-up of 6 months. Long-term follow-up data are not
      presented. Comparative analysis of the short-term functional results indicated
      that there were no differences between the two groups. CONCLUSION: This study
      confirms that the minimally invasive approach is safe and effective for the
      treatment of primary gastroesophageal reflux disease in children.

PMID- 11997816
TI  - Long-term results of laparoscopic antireflux surgery.
AB  - BACKGROUND: It is estimated that laparoscopic antireflux surgery has replaced the
      open approach in centers worldwide. Findings show it to be an established
      treatment option for chronic gastroesophageal reflux disease with an excellent
      clinical outcome and success rates between 85% and 95%. This prospective study
      aimed to evaluate surgical outcome and analysis of failure after 500 laparoscopic
      antireflux procedures followed up for as long as 5 years. METHODS: Between
      September 1993 and May 2000, 500 laparoscopic antireflux procedures were
      performed in our surgical unit. In 345 patients, a laparoscopic "floppy" Nissen
      fundoplication was performed, and in 155 patients, a Toupet fundoplication was
      carried out with standard mobilization of the upper part of the gastric fundus
      and with division of the short gastric vessels. Preoperative and postoperative
      data including 24-h pH monitoring, esophageal manometry, and analysis of failure
      were prospectively reviewed. RESULTS: Conversion to open surgery was necessary in
      two patients (0.4%). Morbidity was 7%, including 24 patients (4.8%) for whom a
      laparoscopic redoprocedure was necessary because of failed primary intervention.
      There was no mortality. During a follow-up period of 3 months to 5 years, 24-h pH
      monitoring and esophageal manometry showed normal values in 95% of the patients
      including patients who had undergone redosurgery. CONCLUSION: The results of the
      current study demonstrate that laparoscopic antireflux surgery is feasible and
      effective, and that it can be performed safely without mortality and with low
      morbidity, yielding good to excellent results over a follow-up period up to 5
      years.

PMID- 11997817
TI  - Nissen vs Toupet laparoscopic fundoplication.
AB  - BACKGROUND: Nissen fundoplication (360 degrees ) is the standard operation for
      the surgical management of gastroesophageal reflux disease (GERD). To avoid
      postoperative dysphagia, it has been proposed that antireflux surgery be tailored
      according to the degree of preexisting esophageal motility. Postoperative
      dysphagia is thought to occur more commonly in patients with esophageal
      dysmotility and the Toupet procedure (270 degrees ) has been recommended for
      these patients. We performed a randomized trial to evaluate this tailored concept
      and to compare the two operative techniques in terms of reflux control and
      complication rate (dysphagia). Our objective was to determine the impact of
      preoperative esophageal motility on the clinical and objective outcome, following
      Toupet vs Nissen fundoplication and to evaluate the success rate of these
      procedures. METHODS: From May 1999 until May 2000, 200 patients with GERD were
      included in a prospective randomized study. After preoperative examinations
      (clinical interview, endoscopy, 24-h pH study and esophageal manometry), 100
      patients underwent either a laparoscopic Nissen (50 with and 50 without motility
      disorders), or a Toupet procedure (50 with and 50 without motility disorders).
      Postoperative follow-up after 4 months included clinical interview, endoscopy, 24
      h pH study and esophageal manometry. RESULTS: Interviews showed that 88% (Nissen)
      and 90% (Toupet) of the patients, respectively, were satisfied with the operative
      result. Dysphagia was more frequent following a Nissen fundoplication than after
      a Toupet (30 vs 11, p <0.001) and did not correlate with preoperative motility.
      In terms of reflux control, the Toupet proved to be as effective as the Nissen
      procedure. CONCLUSION: Tailoring antireflux surgery to esophageal motility is not
      indicated, since motility disorders are not correlated with postoperative
      dysphagia. The Toupet procedure is the better operation because it has a lower
      rate of dysphagia and is as effective as the Nissen fundoplication in controlling
      reflux.

PMID- 11997818
TI  - Mechanisms responsible for recurrent gastroesophageal reflux in neurologically
      impaired children who underwent laparoscopic Nissen fundoplication.
AB  - BACKGROUND: In this study, we attempted to define the lower esophageal sphincter
      (LES) motor events associated with the occurrence of gastroesophageal reflux
      (GER) in neurologically impaired children in whom of GER disease recurred after
      laparoscopic Nissen fundoplication (LNF). METHODS: Of 45 neurologically impaired
      children who had previously undergone LNF, six children in whom recurrence of GER
      disease was documented by 24-h esophageal pH monitoring were studied. Concurrent
      esophageal manometry and pH monitoring were conducted for 1 h both before and
      after the administration of apple juice (10 ml/kg). RESULTS: A total of 89 reflux
      episodes were recorded in the course of the study. Of these, 51 episodes (57%)
      were associated with transient LES relaxation. In the remainder, reflux occurred
      across a contracted LES in 21 episodes (24%) and during absent basal LES tone in
      15 episodes (17%). In four of six patients, transient LES relaxation was
      responsible for more than half of the reflux episodes. CONCLUSION: Transient LES
      relaxation is the predominant mechanism of reflux in neurologically impaired
      children with recurrent GER after LNF.

PMID- 11997819
TI  - Redo laparoscopic surgery for achalasia.
AB  - BACKGROUND: Operative treatment of achalasia can fail in 10% to 15% of patients.
      No information is available on the outcome of laparoscopic reoperation for
      achalasia. METHODS: Data from patients undergoing redo surgery for achalasia were
      prospectively collected. The data were analyzed, and a questionnaire was sent to
      all the patients. RESULTS: Eight patients underwent redo procedures at our
      institution between 1994 and 1998. The reasons for failure of the initial
      operations were incomplete myotomy (n = 5), incorrect diagnosis (n = 2), and new
      onset of reflux symptoms (n = 1). All the redo procedures were performed
      laparoscopically. All the patients except one had excellent or good results. The
      average symptom severity score for dysphagia, regurgitation, chest pain, cough,
      and heartburn all improved after redo procedures. The average quality of life
      score improved from poor to good. CONCLUSIONS: Laparoscopic reoperation for
      achalasia is safe and feasible. It results in symptom improvement for most
      patients. Surgeon experience and recognition of the cause for failure of the
      original operation are most important in predicting the outcome.

PMID- 11997820
TI  - Frequency of postoperative nausea and vomiting in patients undergoing
      laparoscopic foregut surgery.
AB  - BACKGROUND: Wrap disruption or intrathoracic herniation of a fundoplication is a
      dreaded complication of laparoscopic foregut surgery. This problem may often be
      related to postoperative nausea and vomiting (PONV). This study aimed to
      investigate the occurrence of PONV and its management in patients undergoing
      laparoscopic foregut procedures. METHODS: Between January 31 and May 23, 2000,
      104 patients undergoing laparoscopic foregut procedures (fundoplication, myotomy,
      or paraesophageal hernia repair) were followed prospectively. Their postoperative
      course was documented along with the occurrence and management of PONV. All
      laparoscopic foregut surgery patients are managed postoperatively with a uniform
      clinical pathway, and their care is focused on a nursing unit with skill and
      experience in postoperative management. RESULTS: Nausea was documented in the
      postanesthesia care unit (PACU) for 30.1% of the patients, and for 59.6% of the
      patients during their nursing unit stay. Antiemetics were given to all the
      patients with documented nausea. Emesis was noted in 1.9% of the patients in the
      PACU, as compared with 3.8% of the patients on the floor. In one of the patients
      with nursing unit emesis, an acute wrap herniation into the chest occurred,
      necessitating a return to the operating room for correction. The patients with a
      history of postoperative nausea did not have a higher rate of PONV than in those
      with no history of postoperative nausea. The use of preoperative or
      intraoperative antiemetics did not appear to alter the occurrence of PONV.
      Postoperative nausea occurred in 60% of the patients administered preoperative
      antiemetic, as compared with 64% of the patients who received no preoperative
      antiemetic. The average length of hospital stay was longer in those with PONV
      than in those with no PONV (2.6 vs 1.8 days). CONCLUSION: Nausea after
      laparoscopic foregut procedures is common, occurring twice as often on the
      nursing unit as in the PACU. The occurrence of PONV leads to a longer hospital
      stay, and can result in significant sequelae requiring reoperation. The use of
      preoperative or intraoperative antiemetics does not alter the frequency of
      postoperative nausea, suggesting the need to develop effective preemptive
      regimens for patients undergoing laparoscopic foregut procedures. The high rate
      of PONV and its potential risk of damage to a fundoplication and hiatal hernia
      repair should lead surgeons to consider whether laparoscopic foregut procedures
      should ever be performed on an outpatient basis.

PMID- 11997821
TI  - A combination of heparin and an intermittent pneumatic compression device may be
      more effective to prevent deep-vein thrombosis in the lower extremities after
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The purpose of this study was to clarify the effect of a combination
      of heparin and an intermittent pneumatic compression device on thrombogenesis and
      platelet activation in the upper and lower extremities after laparoscopy.
      METHODS: A blinded study was performed on 30 patients. Patients were randomly
      injected with either heparin or physiological saline solution (PSS)
      subcutaneously. The intermittent compression boot was used during surgery. Plasma
      D-dimer (D-D), a marker of thrombogenesis, and b-thromboglobulin (b-TG), a marker
      of platelet activation, were measured in the upper and lower extremities.
      RESULTS: In the heparin group, D-Ds in the upper and lower extremities increased
      significantly 24 h after surgery, but they were significantly lower than those of
      the PSS group. b-TG in the lower extremities of patients in the PSS group
      increased significantly 24 h after surgery. CONCLUSION: A combination of low
      molecular-weight heparin and intermittent pneumatic compression may be more
      effective to prevent deep-vein thrombosis in the legs.

PMID- 11997822
TI  - Pitfalls and complications with laparoscopic intraperitoneal expanded
      polytetrafluoroethylene patch repair of postoperative ventral hernia.
AB  - BACKGROUND: This study reviewed our experience with laparoscopic ventral
      postoperative (incisional) hernia repair. METHODS: Clinical data from the first
      100 cases were analyzed retrospectively. RESULTS: Between 1997 and 2000, 64 women
      and 36 men (mean age, 58.4 +/- 13.6 years; range, 27-87 years) underwent
      laparoscopic hernioplasty. Hernias (mean diameter, 6.2 +/- 3.7 cm) were in a
      midline (74%), subcostal (10%), or other incision location, and were recurrent in
      25%, of the patients. The mean operative time was 119 +/- 77 min. Extensive
      adhesiolysis was necessary in 37 cases. There was no mortality. The recorded
      complications included inadvertent enterotomies (n = 6), seromas (n = 11),
      prolonged ileus (n = 4), and prolonged fever (n = 3). Seven cases were converted;
      to repair accidental enterotomies (n = 4) due to difficult adhesiolysis (n = 2),
      or to control bleeding (n = 1). Six patients underwent reoperation because of
      enetric leak (n = 3) or bowel obstruction (n = 3). There were two documented
      recurrences (2%). The mean follow-up period was 19 months (range, 12-54 months).
      CONCLUSIONS: Laparoscopic intraperitoneal approach to postoperative ventral
      (incisional) hernia repair may be associated with significant complications and
      morbidity, which can be prevented in part by meticulous technique and liberal
      conversions. The justification of this procedure is the low recurrence rate,
      according to preliminary results.

PMID- 11997823
TI  - Endoscopic approach for carotid artery surgery.
AB  - BACKGROUND: Although recent advances in the treatment of carotid artery stenosis
      have included endovascular angioplasty and stent placement, carotid
      endarterectomy is still the approach of choice for carotid disease and is one of
      the most commonly performed operations today. Minimally invasive surgeries
      involving the neck have recently been performed for thyroid and parathyroid
      diseases. The purpose of this study was to evaluate the feasibility of an
      endoscopic approach for carotid artery surgery in a large animal model. METHODS:
      Eight 25- to 30-kg pigs were used. Animals underwent endoscopic carotid
      dissection with carbon dioxide insufflation at 10 mmHg. A 1.5- to 2-cm
      arteriotomy was made in the common carotid artery. Four animals underwent direct
      arteriotomy closure, and four animals underwent synthetic patch graft placement
      using intracorporeal suturing techniques. Open examination of the operative site
      and carotid angiograms were performed at the end of the procedure. Operative time
      was recorded in the last four cases. RESULTS: All animals tolerated the procedure
      well and carotid artery repair was successfully performed in all cases using a
      four-trocar technique. The entire extent of the cervical common and internal
      carotid arteries was exposed up to the cranial base. Cranial nerves and cervical
      structures were clearly visualized and preserved. No bleeding occurred at the end
      of the procedure. Carotid angiograms confirmed patent, nonstenotic vessels in all
      cases. CONCLUSION: Endoscopic approach for carotid surgery is technically
      feasible in the porcine model. This approach may represent a valuable option for
      surgery of the carotid artery since it offers the advantages of minimally
      invasive techniques while maintaining the benefits of surgical arterial repair.

PMID- 11997824
TI  - Complications and conversions of pediatric videosurgery: the Italian multicentric
      experience on 1689 procedures.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence and management of
      complications of videosurgical procedures that occurred during a 4-year period in
      eight Italian pediatric surgery centers. METHODS: Between 1996 and 1999, 2305
      videosurgical procedures were performed in 11 centers of pediatric surgery. The
      data from 3 centers, for a total of 616 procedures, were largely incomplete and
      were thus excluded from the study. We analyzed the data from 8 centers only, for
      a total of 1689 laparoscopic or thoracoscopic operations on patients aged between
      15 days and 16 years. The type of operations performed ranged from basic
      videosurgical interventions, such as varicocelectomy and cryptorchidism, to
      advanced laparoscopic procedures, such as splenectomy, total colectomy, and
      esophageal achalasia. Each patient's file was examined for any complications that
      may have occurred during the surgical procedure and for a record of how these
      were managed. RESULTS: We recorded 79 complications (4.6%) in our series. In 57
      cases (72.2%) the problem was solved by videosurgery. Twenty-two cases (27.8%)
      required conversion to open surgery. There was no mortality in our series. At a
      maximum follow-up of 4 years, all children were alive and had no problems related
      to the videosurgical complications. CONCLUSIONS: We believe that the routine use
      of open laparoscopy in pediatric patients is a key factor to avoiding
      complications related to the Veress needle and blind introduction of the first
      trocar. Moreover, the surgeon's laparoscopic experience, the correct indications
      for laparoscopic surgery, and the verification of the laparoscopic equipment
      before surgery are also important rules to follow to reduce the incidence of
      complications. In the beginning, it is preferable to have the assistance of an
      expert laparoscopic surgeon to decrease the complications related to the learning
      curve period.

PMID- 11997825
TI  - Intraoperative cholangiography is still indicated after preoperative endoscopic
      cholangiography for gallstone disease.
AB  - BACKGROUND: Intraoperative cholangiography (IOC) is frequently omitted in
      patients undergoing laparoscopic cholecystectomy (LC) if they have had successful
      preoperative endoscopic retrograde cholangiography (ERC). METHODS: A
      prospectively maintained divisional laparoscopic cholecystectomy database was
      searched from 1991 to 1997 for patients who had IOC after preoperative ERC. The
      presence of recurrent or residual common duct stones seen on IOC and their impact
      on subsequent management were evaluated. RESULTS: We identified a group of 127
      patients who underwent preoperative ERC. Thirty-one patients (31/127, or 24%)
      went on to receive an IOC during cholecystectomy. In 15 patients whose
      preoperative ERC was reported normal, five (33%) had an abnormal IOC. In 16
      patients whose ERC was reported as having cleared the duct, eight (50%) had an
      IOC abnormality. Eight of these 31 patients required a further procedure to clear
      the duct. CONCLUSION: Retained or recurrent common duct stones at cholecystectomy
      following diagnostic or therapeutic ERC were more common than expected.
      Therefore, IOC is recommended during LC regardless of the findings yielded by the
      preoperative ERC.

PMID- 11997826
TI  - Laparoscopic vs open resection of gastric stromal tumors.
AB  - BACKGROUND: Gastric stromal tumors are rare neoplasms that may be benign or
      malignant. Given that malignant gastric stromal tumors rarely involve lymph nodes
      and require excision with negative margins, they appear amendable to laparoscopic
      excision. There are few reports of laparoscopic resection, and no comparisons
      have been done between laparoscopic and open surgery. This study compares the
      relative efficacy of the two approaches. METHODS: Between May 1994 and December
      2000, 33 patients underwent 35 operations for gastric stromal tumors.
      Laparoscopic resections were performed in 21 patients; open resections were done
      in 12 patients. The medical records of the patients were reviewed retrospectively
      with regard to operating time, blood loss, length of stay, and clinical course.
      RESULTS: Patient demographics, tumor characteristics (mean tumor size, benign vs
      malignant), and presenting symptoms were similar for both groups. In the
      laparoscopic group, 15 wedge resections; three partial gastrectomies, and three
      transgastric needlescopic enucleations were performed. In the open group, six
      wedge resections, four antrectomies, and two partial proximal gastrectomies were
      performed. There were no significant differences in mean operative time (169 vs
      160 min), mean estimated blood loss (106 vs 129 cc), or perioperative
      complication rate (9.5% vs 8.3%) between the laparoscopic and open groups,
      respectively. The mean length of stay was significantly less (p<0.05) in the
      laparoscopic group (3.8 vs 6.2 days). Average follow-up was 1.5 years. One
      patient in each group has died due to metastatic disease. There have been no
      trocar site recurrences. CONCLUSIONS: Laparoscopic resection of gastric stromal
      tumors is safe and appropriate. Tumor size, operating time, and estimated blood
      loss were equivalent to the open approach, and there was a statistically shorter
      hospital stay in the laparoscopic group.

PMID- 11997827
TI  - Intraoperative endoscopy in laparoscopic colectomy.
AB  - BACKGROUND: The localization of focal colonic pathologies is problematical in
      laparoscopic surgery because it is difficult to palpate the colon. The aim of
      this study was to evaluate the use of intraoperative lower endoscopy in
      laparoscopic segmental colectomy. METHODS: We did a retrospective review of the
      charts of patients who had undergone laparoscopic segmental colectomy. Patients
      in whom intraoperative lower endoscopy had been used were compared to a group of
      250 patients who had colectomy by laparotomy. The patients were matched by type
      of surgery and operating surgeon. RESULTS: Between 1991 and 2000, 233 patients
      underwent laparoscopic segmental colectomy at our clinic. Lower endoscopy was
      employed in 57 of them (24%), as compared to 42 patients (17%) in the laparotomy
      matched group ( p = 0.042). The diseased segment was successfully identified in
      all of the patients in whom the main indication for endoscopy was localization
      (65% of cases). Endoscopy was judged to have changed the surgical management in
      66% of the 57 cases in whom it was employed, and especially in 88% of the 37
      patients for whom the main indication had been localization. There were no
      endoscopy-related complications. CONCLUSION: Intraoperative lower endoscopy is a
      useful and safe tool for the localization of pathologies and the assessment of
      the intracorporeal anastomosis in laparoscopic segmental colectomy.

PMID- 11997828
TI  - A new bipolar feedback-controlled sealing system for closure of the cystic duct
      and artery.
AB  - BACKGROUND: Bile leaks are serious complications after laparoscopic
      cholecystectomy. The aim of this study was to evaluate the feasibility of closure
      of the cystic duct with a new feedback-controlled bipolar sealing system
      (LigaSure). METHODS: Ten domestic pigs underwent open cholecystectomy with the
      cystic duct and artery dissected and sealed with the new bipolar sealing system
      (LigaSure). Four and 8 days postoperatively, 5 pigs each were sacrificed and the
      closure of the cystic duct was evaluated. The cystic stump and the common bile
      duct were excised for histological examination. RESULTS: None of the pigs had a
      bile leak or a biliary peritonitis. There were no signs of postoperative bleeding
      or inflammation in Calot's triangle. Histology showed total necrosis of the
      cystic duct in the first two pigs due to too much energy used. The remaining
      specimens showed a regularly scaling zone without necrosis in 7 cases, and in one
      case a partial necrosis in the mucosa only was found. CONCLUSION: Cystic artery
      and cystic duct closure with the new device may be an alternative to the clip.
      Further trials should evaluate the feasibility and safety of the new device in
      the clinical setting.

PMID- 11997829
TI  - The mechanisms of blood vessel closure in humans by the application of ultrasonic
      energy.
AB  - BACKGROUND: The use of the ultrasonically activated scalpel (UAS) for vessel
      closure has attained widespread acceptance in many surgical fields. The aim of
      our study was to investigate the electron microscopic changes to the blood
      vessels after the application of UAS. METHODS: We collected 10 arterial and 10
      venous segments from vessels that had previously been closed by UAS during
      abdominal operations. The samples were then prepared for ultramicroscopic
      analysis. Pathological changes in the lumen and the three wall layers of the
      blood vessel were examined under scanning and transmission electron microscopy.
      RESULTS: All of the vessel segments showed similar changes: the presence of a
      blood clot, endothelial cell condensation, coagulative necrosis of the wall, and
      charring of the vessel at its tip. The edge of the cut vessel were closed by the
      coagulation bond, which was tied up by collagen fibrils escaped from
      denaturation. CONCLUSION: When ultrasonic energy is applied to tissues, it
      changes their structure so as to make a new extracellular matrix.

PMID- 11997830
TI  - Is laparoscopic cholecystectomy a mature operative technique?
AB  - BACKGROUND: More than 10 years after its introduction, laparoscopic
      cholecystectomy has become the method of choice for the treatment of
      cholecystolithiasis. However intraoperative difficulties with dramatic
      postoperative consequences have been reported. The aim of this study was to
      identify what role the two-dimensional view, the surgeon's experience, the
      instruments, technical tools and their (time) influence exercised on the
      operation course in daily laparoscopic operations. METHODS: The operative times
      for 30 laparoscopic cholecystectomies were investigated by ergonomic sequence
      analysis and analyzed statistically with the use of the Wilcoxon test. RESULTS:
      Comparing experienced and less experienced surgeons, a significant difference in
      the duration of the operation was observed (56 +/- 24 min compared to 75 +/- 13
      min p = 0,025), especially in the laparoscopic intra-abdominal phase of the
      operation. The prolonged duration of the operation (15-20%) was mainly due to
      problems with the technical tools (40%) and the use of instruments (23.5%).
      Visualization had a minor influence (14.4%) on the duration of the operation, and
      the negative effect of the two-dimensional view (0.5%) was negligible. The last
      two factors did not cause any complications. CONCLUSIONS: The recognized
      difficulties still cause a loss of time and in some cases complications, which
      can only partly be compensated by the surgeon's experience. This leads to
      reluctance in the application of laparoscopic cholecystectomy in more complicated
      stages of the disease. Two-dimensional view satisfies the surgeon's demands for a
      safe procedure.

PMID- 11997831
TI  - Do complications related to laparoscopic cholecystectomy influence the prognosis
      of gallbladder cancer?
AB  - BACKGROUND: Laparoscopy is thought to worsen the prognosis of gallbladder cancer
      (GBC) discovered unexpectedly at laparoscopic cholecystectomy (LC). However,
      laproscopy has never been shown to have an influence on patient survival in
      clinical series. METHODS: We Performed a two-center retrospective analysis of 28
      patients with GBC (11 previously known, 17 unexpectedly discovered by LC) to
      determine whether laparoscopy and complications related to LC had any influence
      on the prognosis of GBC. Resectability for cure after LC, survival, and
      recurrence related to both the procedure itself and complications associated with
      LC were analyzed. RESULTS: Of the 17 patients with unexpected GBC, 16 were
      considered resectable for cure at the time of LC. Advanced disease was detected
      in eight patients by re staging (n = 5) or exploration (n = 3). Seven patients
      (43.8%) underwent reoperation for cure. Mean survival of patients with unexpected
      GBC was 26.5 months. Mean survival was shorter when complications (bile spillage,
      injury of common bile duct, or tumor violation) occurred during LC (10.2 vs 33
      months, p = 0.016). If bile spillage was the only complication at LC, there was
      also a trend to shorter survival (12 vs 33 months, p = 0.061). CONCLUSION:
      Complications during LC significantly worsen the prognosis of GBC. Therefore,
      bile spillage and excessive manipulation of the gallbladder should be avoided.

PMID- 11997832
TI  - One-trocar appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is a feasible and a safe alternative to
      open appendectomy. Several laparoscopic procedures have been described that use
      one or more trocars. We report our experience with the treatment of acute
      appendicitis using a laparoscopy-assisted technique by means of only one
      transumbilical trocar. METHODS: From February 1996 to February 1999 we performed
      65 laparoscopic appendectomies. In the procedures, a 10-mm operative telescope
      was used, with a 450-mm atraumatic grasper introduced through the operative
      channel. After the intraabdominal laparoscopic dissection, the appendix was
      exteriorized through the umbilical trocar. The appendectomy was performed outside
      the abdomen as in the open procedure. The procedure was completed using only one
      trocar in 55 patients (84.6%). Regarding the other 10 cases (15.3%), in 5 we used
      more than one trocar and in 5 conversion to open surgery was needed. RESULTS: The
      average operating time in our series was 25 min and the median time to discharge
      was 2 days. There were six (11%) postoperative complications (three serous
      umbilical secretion and three umbilical hematomas). CONCLUSIONS: Our results
      suggest that this technique, which combines the advantages of both the open and
      the laparoscopic procedures, is a valid alternative for the treatment of acute
      appendicitis. However, this procedure cannot always be completed using only one
      trocar, as happened in 10 cases in our series.

PMID- 11997833
TI  - Peritoneal, systemic, and distant organ inflammatory responses are reduced by a
      laparoscopic approach and carbon dioxide versus air.
AB  - BACKGROUND: Advantages of laparoscopic surgery have, among other factors, been
      attributed to a shorter length of abdominal incision and the use of CO2 versus
      air. An analysis of these factors taking pressure-induced alterations into
      account is lacking. The objective of the study was to determine the impact of
      laparoscopy and laparotomy with exposure to CO2 and room air under a similar
      pressure on local, systemic, and distant organ immune responses. METHODS: Twenty
      piglets were randomized into four groups: CO2 laparoscopy, air laparoscopy, CO2
      laparotomy, and air laparotomy. Laparotomy was performed in a sterile balloon
      pressurized similar to laparoscopy. Peritoneal interleukin-1, interleukin-6,
      tumor necrosis factor-a, and counts of polymorphnuclear cells (PMNs), and
      macrophages (MFs) were determined in abdominal lavage fluids at 0, 2, and 48 h.
      Macrophages were assessed for reactive oxygen species (ROS) production. Systemic
      responses were gauged by white blood cell count (WBC) and cytokines. Alveolar
      lavage was performed at 48 h to determine cytokine levels, cell counts, and MF
      ROS production. Blood, lavage fluids, and mesenteric lymph nodes were tested for
      bacterial translocation. RESULTS: Regarding the peritoneal response, laparotomy
      versus laparoscopy when performed with CO2 significantly increased PMN and
      decreased the percentage of macrophages (%MF) up to 48 h. There was a significant
      increase in interleukin-6, and there was a fourfold increase in MF ROS
      production. Similar differences between the procedures were found with exposure
      to air. The use of air versus CO2 in laparoscopy, but not in laparotomy, resulted
      in an increase of peritoneal PMN and a decrease of the %MF up to 48 h. Air
      increased the local interleukin-6 release in both procedures and increased MF ROS
      production fourfold. Regarding the systemic response, laparotomy produced a
      significant increase in WBC, which was significantly more pronounced with
      exposure to air. No alteration of other systemic cytokines was seen. Regarding
      the pulmonary response, the number of MFs and MF ROS production were
      significantly increased after air versus CO2 laparoscopy. There were no such
      differences between the laparotomy groups. Regarding bacterial translocation, no
      bacteria were cultured from peritoneal fluids, lymph nodes, or blood.
      CONCLUSIONS: Inflammatory responses were reduced by a laparoscopic approach and
      by exposure to CO2 versus air. Peritoneal responses were affected to a larger
      degree than systemic parameters. Laparotomy overruled the effects of CO2 on
      chemotaxis and distant organ injury but not on peritoneal cytokine release.

PMID- 11997834
TI  - The endoscopic management of persistent bile leakage after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Bile leakage after laparoscopic biliary surgery is a surgical
      challenge in which endoscopy can play an important role. METHODS: A total of 26
      patients underwent endoscopic retrograde cholangiopancreatography (ERCP) in our
      department. Patients with evidence of major ductal injury were treated
      surgically. In all other cases, endoscopic sphincterotomy was performed, any
      retained bile duct stones were removed, and a biliary endoprosthesis or a
      nasobiliary catheter was inserted on a selective basis. RESULTS: ERCP was
      successful in 24 patients. Seven patients were treated surgically after
      cholangiography revealed major ductal injury. Two more patients were eventually
      operated on due to bile peritonitis. Of the other 15 patients, 11 had leakage
      from the cystic duct and four had leakage from the gallbladder bed. Bile duct
      stones were removed from eight patients, an endoprosthesis were inserted in five
      patients, and a nasobiliary catheter was inserted in two patients. Bile leakage
      was treated successfully in all 15 patients with no further complications.
      CONCLUSION: ERCP is a means of safe diagnosing the cause of a bile leakage and
      offers a definitive treatment in most cases.

PMID- 11997835
TI  - Slow-transit constipation after radical hysterectomy type III.
AB  - BACKGROUND: This study investigated ways to reduce the rate of slow-transit
      constipation after radical hysterectomy type III. METHODS: A prospective study
      was conducted involving 59 consecutive patients with cervical cancer stage IB1
      IIIA at high risk for parametrial or lymph node involvement who were treated
      between May 1996 and March 1999 by laparoscopically assisted radical vaginal
      hysterectomy type III. RESULTS: During laparoscopic transection of the cardinal
      ligament, particular attention was focused on conservation of the pelvic
      splanchnic nerves. After vaginal removal of the uterus, a vaginal
      sacrocolporectopexy was performed transvaginally. Nerve preservation and pexy of
      the rectum allowed a significant reduction of postoperative constipation, as
      compared with classic radical hysterectomy without conservation of the splanchnic
      pelvic nerves and without sacrocolporectopexy. CONCLUSION: Refinements in the
      preparation of the parasympathetic nerves during radical pelvic surgery and
      refixation of the terminal rectum helps to prevent postoperative constipation.

PMID- 11997836
TI  - Laparoscopic splenectomy.
AB  - BACKGROUND: Laparoscopic splenectomy is currently the procedure of choice for
      elective splenectomy. This study reviews the initial 100 laparoscopic
      splenectomies completed at the Cleveland Clinic Foundation. METHODS: A
      retrospective review of elective laparoscopic splenectomy was performed to assess
      clinical outcomes at the Cleveland Clinic Foundation. Patient demographics,
      preoperative diagnoses, operative characteristics, morbidity, and mortality were
      evaluated. RESULTS: Of the 169 elective splenectomies completed over a 4-year
      period from 1995 to 1999, 100 were attempted laparoscopically. The proportions of
      all splenectomies attempted laparoscopically by year were 17%, 38%, 75%, and 72%.
      Nearly 70% of splenectomies were performed for idiopathic thrombocytopenic
      purpura or malignancy. Overall, the mean blood loss was 181 ml, and the mean
      operative time was 170 min. Splenomegaly occurred in 31% of the patients and
      accounted for longer operative times. Three patients required conversion to an
      open procedure. Postoperative complications were seen in 13% of the patients. One
      patient died in the postoperative period from staphylococcal sepsis, giving a
      mortality rate of 1%. CONCLUSIONS: Laparoscopic splenectomy currently is the
      procedure of choice for elective splenectomy at our institution. As compared with
      traditional open splenectomy, laparoscopic splenectomy results in minimal
      morbidity even in the setting of splenomegaly.

PMID- 11997837
TI  - Is obesity a high-risk factor for laparoscopic colorectal surgery?
AB  - BACKGROUND: The aim of this study was to assess the outcome of laparoscopic
      colorectal surgery in obese patients and compare it to that of a nonobese group
      of patients who underwent similar procedures. METHODS: All 162 consecutive
      patients who underwent an elective laparoscopic or laparoscopic-assisted
      segmental colorectal resection between August 1991 and December 1997 were
      evaluated. Body mass index (BMI; kg/m2) was used as an objective index to
      indicate massive obesity. The parameters analyzed included BMI, age, gender,
      comorbid conditions, diagnosis, procedure, American Society of Anesthesiologists
      classification score, operative time, estimated blood loss, transfusion
      requirements, intraoperative complications, conversion to laparotomy,
      postoperative complications, length of hospitalization, and mortality. RESULTS:
      Thirty-one patients (19.1%) were obese (23 males and 8 females). Conversion rates
      were significantly increased in the obese group (39 vs 13.5%, p = 0.01), with an
      overall conversion rate of 18%. The postoperative complication rate in the obese
      group was 78% versus 24% in the nonobese group (p <0.01). Specifically, rates of
      ileus and wound infections were significantly higher in the obese group [32.3 vs.
      7.6% (p <0.01) and 12.9 vs 3.1%. (p = 0.03), respectively]. Furthermore, hospital
      stay in the obese group was longer (9.5 days) than in the nonobese group (6.9
      days, p = 0.02). CONCLUSION: Laparoscopic colorectal segmental resections are
      feasible in obese patients. However, increased rates of conversion to laparotomy
      should be anticipated and the risk of postoperative complications is
      significantly increased, prolonging the length of hospitalization when compared
      to that of nonobese patients.

PMID- 11997838
TI  - Laparoscopic transabdominal pericardial window: new standard in the treatment of
      recurrent pericardial effusion complicated by cardiac tamponade.
AB  - Creation of a transabdominal transdiaphragmatic pericardial window for life
      threatening recurrent pericardial effusion has proved to be a safe minimally
      invasive technique. By inducing adequate pericardial sac decompression while
      avoiding single-lung ventilation and thoracic drainage in severely ill patients,
      it provides anatomopathologic diagnosis and can direct further therapeutic
      measures. The transabdominal approach improves postoperative recovery
      dramatically by limiting postoperative pain and prevents sometimes invalidating
      intercostal neuralgia. Transabdominal pericardial sac fenestration should be part
      of the armamentarium used by every minimally invasive surgeon.

PMID- 11997839
TI  - Development of port-site metastasis after pneumoperitoneum.
AB  - BACKGROUND: Port-site metastasis is a critical problem in laparoscopic cancer
      surgery; the pathogenesis and means of prevention are still unclear. The aim of
      this study was to clarify by scanning electron microscopy the initial morphologic
      changes in the development of port-site metastasis. METHODS: Fifteen nude mice
      were injected with human gastric cancer (MKN 45) cells. Mice were killed on days
      0, 3, and 8 (n = 5 each day) after intraperitoneal injection of 5 x 105 cancer
      cells and carbon dioxide (CO2) pneumoperitoneum at 4-6 mmHg for 20 min. The
      abdominal wall with the port sites was harvested and examined under both light
      and scanning electron microscopy. RESULTS: Immediately after CO2 pneumoperitoneum
      (day 0), the abdominal peritoneum was peeled away and the muscular layer was
      destroyed at the port site in all mice. Several cancer cells were attached to the
      injured port sites. On day 3, the subperitoneal tissue and muscular layer defects
      were replaced by granulation tissue, and several cancer cells were observed in
      the subperitoneal tissue. On day 8, a small nodule was macroscopically visible at
      the port site; it was completely covered by mesothelial cells and consisted of
      numerous cancer cells. CONCLUSIONS: Free cancer cells appear to attach to the
      injured port sites immediately after CO2 pneumoperitoneum, and these are
      associated with the development of port-site metastasis after laparoscopic cancer
      surgery.

PMID- 11997840
TI  - Laparoscopic diaphragm rupture repair.
AB  - Diaphragm rupture is an infrequently encountered but well-documented injury in
      the multiply injured patient. Only a few cases in which minimally invasive
      techniques were used for repair have been reported thus far. Herein we describe
      the repair of a diaphragm rupture in a 36-year-old man who was injured in a motor
      vehicle accident. In a 10-year review of the literature, we were able to locate
      seven journal articles reporting 10 patients. We conclude that in appropriate
      stable patients with diaphragm rupture, minimally invasive techniques offer a
      reasonable alternative to open laparotomy or thoracotomy.

PMID- 11997841
TI  - Laparoscopic pyloric exclusion after endoscopic retrograde
      cholangiopancreatography perforation.
AB  - We describe a laparoscopic technique of pyloric exclusion with gastroenterostomy
      and common bile duct T tube insertion for obvious perforation at endoscopic
      retrograde cholangiopancreatography with papillotomy. The patient was operated on
      immediately after diagnosis of the lesion. The postoperative sequellae were very
      comparable to those of elective laparoscopic common bile duct exploration. We
      believe this approach is interesting, especially in the current era of frequent
      litigation.

PMID- 11997842
TI  - Laparoscopic repair of congenital diaphragmatic hernias.
AB  - Bochdalek and Morgagni hernias are the least common congenital diaphragmatic
      hernias, with the prevalence of Bochdalek hernia being 1/2200 births and the
      prevalence of Morgagni hernia being 1/1 million births. Although they are usually
      asymptomatic, congenital diaphragmatic hernias, especially Bochdalek and Morgagni
      hernias, are diagnosed in early childhood. In adulthood, they are diagnosed
      incidentally or when they become symptomatic. The repair of congenital
      diaphragmatic hernia is indicated in all children and symptomatic adults. We
      present three cases of congenital diaphragmatic hernia, two Morgagni and one
      Bochdalek hernias, repaired laparoscopically. We describe the operational
      methods. The results of the operations were satisfactory, with cure defined with
      radiological images after 1 month. We propose the use of laparoscopy in the
      repair procedure because it is a safe and effective method. Benefits include that
      it provides an excellent view of the surgical field, ease of execution, minimal
      surgical trauma, excellent cosmetic results, rapid recovery, and shorter
      hospitalization stay.

PMID- 11997843
TI  - Unusual breakage of a plastic biliary endoprosthesis causing an enterocutaneous
      fistula.
AB  - OBJECTIVE: The objective of our study was to illustrate a case of endoscopically
      placed biliary stent breakage. METHODS: A72-year-old woman with a prolonged
      history of cholangitis following laparoscopic cholecistectomy was referred to our
      institution 8 years ago. Dilatation of the intra- and extrahepatic biliary tree
      and a benign stricture at the cystic confluence were observed at US and
      endoscopic retrograde cholangiopancreatography (ERCP). A 12-F gauge plastic
      endoprosthesis was placed. In the absence of any symptoms, breakage of the stent
      was revealed 18 months later at plain radiology. Eight years later an
      enterocutaneous fistula occurred originating from a jejunal loop containing the
      indwelled distal part of the stent. Surgery was undertaken and the distal part of
      the stent removed with the perforated jejunal loop. The proximal part was
      successively endoscopically removed. CONCLUSIONS: Disruption of a biliary
      endoprosthesis is observed in patients in whom the stent is kept in situ for a
      long period or consequent to exchange. The removal and exchange is mandatory when
      the stent disruption is followed by cholangitis. In the current case, because of
      the absence of any symptoms the removal of the stent was not attempted. Immediate
      endoscopic removal of the prosthetic fragments seems to be the treatment of
      choice for replacement of a new stent.

PMID- 11997844
TI  - A breakthrough in cryosurgery.
AB  - Liver cryosurgery is one of the treatment options for unresectable liver
      metastases. Indications for the use of this treatment instead of classic surgery
      are bilobar disease, location of the tumor at an irresectable anatomic site, and
      comorbid conditions of the patient. Possible complications of cryosurgery are
      hemorrhage, coagulopathy, pneumonia, pleural effusion, abdominal abscess, and
      bile fistula. We describe a patient in whom a hepatobronchial fistula developed
      after cryosurgery. The patient had cryosurgery because of an unresectable liver
      metastasis in a Dukes' C rectal carcinoma. More details are given in the case
      report. To our knowledge, a hepatobronchial fistula as a complication of
      cryosurgery has never been reported. It therefore should be added to the list of
      possible cryosurgery complications.

PMID- 11997845
TI  - A rare complication of laparoscopic adjustable gastric banding.
AB  - The most common complications of laparoscopic gastric banding (LGB) are band
      dislocation, port problems, and leakage in the band system. We present a case of
      an aneurysmal dilatation of the balloon portion of the band by filling as a rare
      complication of LGB. A 53-year-old male patient with morbid obesity (body mass
      index 40 kg/m2) was treated with LGB (adjustable Bioenterics gastric band). Six
      months after the operation there was no evidence of weight reduction. X-ray
      examination showed the band to be in the correct position. The port punction
      revealed no spontaneous fluid loss. The contrast filling of band demonstrated no
      signs of leakage but there was an abnormal dilatation of one part of the balloon.
      Only one filling segment of balloon was dilatated and the rest was empty. Two and
      a half years after the initial operation, we carried out laparoscopic band
      exchange. Six weeks later, the band was adjusted with 2 ml saline, and the
      patient reported successful reduction of food volume. He had lost 18 kg 3 months
      postoperatively. We conclude that band function requires careful intraoperative
      monitoring. In patients who do not lose weight after gastric restriction surgery,
      uncommon complications must also be considered.

PMID- 11997846
TI  - Cathamenial pneumothorax.
AB  - Cathamenial pneumothorax is a relatively low-frequency pathology (approximately
      100 cases cited in the literature) characterized by recurrent pneumothorax
      episodes during the menstruation period. We report on a 34-year-old female
      patient who had recurrent pneumothorax that did not respond to chest drainage and
      whose presentation was directly related to the menstruation period. Our patient
      also had a significant clinical record for pelvic endometriosis. She underwent
      video-assisted thoracoscopic exploration (VATS) of the pleural cavity and
      dystrophic parenchymal blebs of the middle lobe were found. An atypical resection
      of the bollous tissue was performed and pleurodesis completed the intervention.
      During VATS no ectopic endometriosis foci or diaphragmatic fenestrations (widely
      considered as a possible cause of this clinical picture) were evidenced.

PMID- 11997847
TI  - A case of cancer on the pharyngoesophageal junction treated by ambulatory
      endoscopic mucosectomy.
AB  - A 52-year-old man underwent endoscopy because of discomfort in the hypopharyngeal
      region, and a 1.5-cm tumor was found on the pharyngoesophageal junction. In 1992,
      the patient was treated for advanced cervicothoracic esophageal cancer by
      preoperative chemotherapy and esophagectomy with radical lymph adenectomy and
      right thoracotomy. Reconstruction with a gastric substitute by cervical
      esophagogastrostomy was performed and postoperative adjuvant radiotherapy
      followed. Histologically, the esophageal tumor had invaded the adventitia and
      showed metastases to regional lymph nodes and vascular involvement with a free
      surgical margin. Hypopharynx was also included in the irradiation field.
      Therefore, we tried to resect another primary tumor on the pharyngoesophageal
      junction by the endoscopic mucosectomy technique with an esophageal multipurpose
      tube (np-EEM). The tumor was resected on August 21, 1996, but follow-up endoscopy
      revealed residual or another primary tumor on the pharyngoesophageal junction in
      October 1996. The first resected specimen revealed a positive cut margin that
      might indicate incomplete resection. Three months later we performed a second
      mucosectomy. No problems occurred during or after tumor resection. Both
      treatments were performed without hospitalization, and the patient returned to
      his normal daily life on the day following tumor resection. Follow-up
      examinations have shown no sign of cancer recurrence on the pharyngoesophageal
      junction for more than 4 years.

PMID- 11997848
TI  - Hand-assisted laparoscopic splenectomy for a splenic hamartoma.
AB  - We present a patient with a hamartoma of the spleen. The case was thought to be a
      good indication for a hand-assisted laparoscopic approach and treatment was
      successful. Until now, only one case of a laparoscopic removal of a splenic
      hamartoma has been reported. Focal lesions of the spleen should be removed intact
      to allow a complete histological examination and to avoid peritoneal
      dissemination in case of malignancy. In these patients, the hand-assisted
      approach makes possible the removal of an unminced organ and has the advantage of
      being a purely laparoscopic technique. It should thus be considered the method of
      choice for surgical treatment.

PMID- 11997849
TI  - Diverticulum of the midthoracic esophagus: pathogenesis and surgical treatment.
AB  - Midthoracic esophageal diverticula represent 15% of all esophageal diverticula.
      Gastrointestinal endoscopy, barium swallow, esophageal manometry (indispensable
      for detecting any motor alterations often at the root of the pathogenesis of the
      diverticulum and for selecting the best surgical option), and 24-h pHmetry are
      the correct examinations to perform. Simple diverticulectomy performed via
      thoracoscopy can be sufficient for small diverticula without associated motor
      alterations. In other cases, it is best to combine diverticulectomy with a
      longitudinal extramucous myotomy extending at least 3 or 4 cm above and below the
      neck of the diverticulum or to the entire esophageal body for diffuse esophageal
      spasm. We report the case of a 67-year-old male patient with a sacciform
      diverticulum at the mid-third on the anterior wall of the thoracic esophagus.
      Manometric examination showed peristaltic waves with an amplitude and duration
      that were above normal at the inferior third of the esophagus. Lower esophageal
      sphincter (LES) and upper esophageal sphincter (UES) were essentially normal. The
      diagnosis was pulsion-type midthoracic esophageal diverticulum. We performed a
      diverticulectomy with endoGIA via right thoracoscopy and extramucous myotomy
      extended from the upper margin of the diverticulum to the esophageal inlet in the
      hiatus, corresponding to the area showing motor alteration. After 3 months, the
      patient reported complete remission of symptoms and had gained 4 kg. Radiography
      of the digestive tube showed a normal transit at the distal esophagus. Manometric
      follow-up revealed the presence of peristaltic waves with a normal amplitude and
      duration along the entire esophagus.

PMID- 11997850
TI  - Is it necessary to lift abdominal wall when preparing a pneumoperitoneum?

PMID- 11997851
TI  - [The role of interventional radiology in emergency radiology].

PMID- 11997852
TI  - [Image processing in radiology].
AB  - Medical imaging processing and analysis methods have significantly improved
      during recent years and are now being increasingly used in clinical applications.
      Preprocessing algorithms are used to influence image contrast and noise. Three
      dimensional visualization techniques including volume rendering and virtual
      endoscopy are increasingly available to evaluate sectional imaging data sets.
      Registration techniques have been developed to merge different examination
      modalities. Structures of interest can be extracted from the image data sets by
      various segmentation methods. Segmented structures are used for automated
      quantification analysis as well as for three-dimensional therapy planning,
      simulation and intervention guidance, including medical modelling, virtual
      reality environments, surgical robots and navigation systems. These newly
      developed methods require specialized skills for the production and
      postprocessing of radiological imaging data as well as new definitions of the
      roles of the traditional specialties. The aim of this article is to give an
      overview of the state-of-the-art of medical imaging processing methods, practical
      implications for the radiologist's daily work and future aspects.

PMID- 11997853
TI  - [MR Angiography: First choice for diagnosis of the arterial vascular system].
AB  - Contrast medium-enhanced, 3D MR angiography enables an extensive and
      diagnostically accurate evaluation of arterial vessels in the neck, thorax,
      abdomen, and limbs. Advances in the field of MR apparatus technology and the
      introduction of contrast-medium enhanced MR angiographic techniques have made
      this development possible. Contrast medium-enhanced MR angiography combines the
      intravenous bolus administration of a paramagnetic contrast medium with the rapid
      acquisition of 3D datasets. The possibilities for obtaining data in the thorax
      and abdomen within one breath-hold, the resulting high contrast between vessel
      lumen and surrounding soft tissue as well as the inherent 3D nature of the images
      allow for diagnostically relevant image quality. In many centers contrast
      enhanced 3D MR angiography has widely replaced the conventional digital
      subtraction roentgenography for the clarification of pathologies in arterial
      vessels. This review presents a survey of the technical background of contrast
      medium eynhanced 3D MRA. In addition, the spectrum of indications is given and
      discussed on the basis of clinical examples.

PMID- 11997854
TI  - Navigator-gated and real-time motion corrected free-breathing MR Imaging of
      myocardial late enhancement.
AB  - PURPOSE: A new magnetic resonance imaging approach for detection of myocardial
      late enhancement during free-breathing was developed. METHODS AND RESULTS: For
      suppression of respiratory motion artifacts, a prospective navigator technology
      including real-time motion correction and a local navigator restore was
      implemented. Subject specific inversion times were defined from images with
      incrementally increased inversion times acquired during a single dynamic scout
      navigator-gated and real-time motion corrected free-breathing scan. Subsequently,
      MR-imaging of myocardial late enhancement was performed with navigator-gated and
      real-time motion corrected adjacent short axis and long axis (two, three and four
      chamber) views. This alternative approach was investigated in 7 patients with
      history of myocardial infarction 12 min after i. v. administration of 0.2 mmol/kg
      body weight gadolinium-DTPA. CONCLUSION: With the presented navigator-gated and
      real-time motion corrected sequence for MR-imaging of myocardial late enhancement
      data can be completely acquired during free-breathing. Time constraints of a
      breath-hold technique are abolished and optimized patient specific inversion time
      is ensured.

PMID- 11997855
TI  - Vessel wall MRI of the thoracic aorta: correlation to histology and
      transesophageal ultrasound. Preliminary results.
AB  - PURPOSE: To visualise the vessel wall of the descending thoracic aorta using
      magnetic resonance imaging. To evaluate the diagnostic potential of tailored T1
      weighted sequences with contrast enhancement to assess systemic atherosclerotic
      disease. METHODS: This study was performed on a clinical 1.5 Tesla scanner using
      a gradient strength of 30 mT/m and the phased array spine coil. A cadaver was
      examined to optimise a magnetic resonance imaging (MRI) protocol to evaluate
      atherosclerotic aortic wall disease. The acquired MR images were compared to
      gross specimens and histology. Subsequently seven patients who had undergone
      transesophageal ultrasound (TEU) with detailed assessment of the descending
      thoracic aorta were examined with MRI. The optimised protocol included
      untriggered and fat suppressed T2-weighted turbo spin echo sequences and ECG
      triggered and fat suppressed T1-weighted spin echo sequences before and after iv
      administration of Gd-DTPA. Findings of the MR images were compared to the results
      of TEU. Contrast enhancement measurements were performed in normal and thickened
      vessel wall segments. RESULTS: For the cadaver study a good correlation of the
      degree of vessel wall thickening and the extent of plaque imaged with the applied
      MR protocol was found. Tissue characterisation was limited due to post mortem
      changes. In vivo ECG-triggered T1-weighted images showed good correlation to TEU
      in terms of vessel wall thickness and plaque extension as verified by means of
      consensus reading. Differentiation of the plaque components fat, calcium and
      fibrous tissue was possible. In thickened aortic wall segments and fibrous caps a
      mean contrast enhancement of 50.4 % +/- 23.5 % was measurable while normal wall
      segments showed an enhancement of 6.7 % +/- 3.1 %. The difference of contrast
      enhancement was highly significant (p < 0.0001). CONCLUSION: Using fat suppressed
      T1-weighted sequences with contrast enhancement the extent of atherosclerotic
      vessel wall changes can be demonstrated. The suggested MR protocol contains a
      high potential for diagnosis and follow-up of therapy of atherosclerotic disease
      of the descending thoracic aorta.

PMID- 11997856
TI  - Quantitative analysis of energy metabolism in human muscle using SLOOP 31P-MR
      spectroscopy.
AB  - OBJECTIVE: Energy metabolism is vital for regular muscle function. In humans, in
      vivo analysis using (31)P-MR-spectroscopy (MRS) is mostly restricted to
      semiquantitative parameters due to technical demands. We applied Spatial
      Localization with Optimal Pointspread Function (SLOOP) for quantification in
      human skeletal and cardiac muscle. SUBJECTS/METHODS: 10 healthy volunteers and 4
      patients with myotonic dystrophy type 1 were examined using a 1.5 T system
      (Magnetom VISION) and chemical shift imaging (CSI) for data collection.
      Concentrations of PCr, ATP and Pi as well as PCr/ATP ratios were calculated by
      SLOOP. RESULTS: Concentrations of PCr, ATP and Pi were 29.9 +/- 3.4, 7.1 +/- 0.9
      and 5.7 +/- 1.2 [mmol/kg] in normal skeletal muscle, corresponding to previously
      published studies. Two of the patients with a duration of disease longer than 10
      years and a pronounced muscle weakness showed a significant decrease of PCr and
      ATP in skeletal muscle below 10 and 5 mmol/kg. One of these patients had an
      additional reduction of PCr in cardiac muscle. CONCLUSIONS: With MRS and SLOOP, a
      more accurate quantitative assessment of metabolism is now available in skeletal
      and cardiac muscle. Longitudinal studies of larger patient groups will allow to
      better describe the metabolic disorder in muscle disease over time. Moreover,
      these techniques offer a new way to quantify treatment effects in future trials.

PMID- 11997857
TI  - [Endovascular aneurysm treatment: Radiological and macropathological findings of
      the endoluminal surface of modular stent grafts].
AB  - PURPOSE: Characterization of the endoluminal surface of a modular stent graft and
      correlation of macropathological findings with results of radiological methods.
      METHODS: Aneurysms of the infrarenal aorta were created in 36 mongrel FBI dogs
      using autologous material. Endovascular treatment was performed with modular
      stent grafts using two polyester-covered nitinol stents connected with overlap
      within the aneurysm. Follow-up was 1 and 6 weeks, and 6 months for 12 animals,
      respectively. Results were documented using sonography, intravascular ultrasound
      (IVUS), spiral CT, MRI, and digital subtraction angiography (DSA). After
      fixation, the aorta was prepared and incised lengthwise. Before histopathological
      work-up, the different segments were macropathologically characterized and
      correlated with the respective findings of the radiological methods. RESULTS: 4
      cases showed high grade stenosis within the stent grafts and graft occlusion
      occurred in two cases. The connection sites of these modular stent grafts showed
      steps and partial separation of the graft components was causative in 5 of these
      cases. Migration of graft components occurred in three cases, one of them with
      complete disconnection of the modular device. Irregulartities and deposits on the
      endoluminal surface were systematically underestimated with all radiological
      techniques used. IVUS showed moderate concordance concerning deployment and
      unfolding of the stent graft, however, irregularities of the endoluminal surface
      were systematically underestimated. Concordance of MRI, sonography, and CT was
      worse. Contrast-enhanced T1-w MRI detected endoluminal deposits with moderate
      concordance. However, the thickness of deposits was underestimated. DSA, IVUS,
      and CT showed only poor concordance with macropathological findings. CONCLUSIONS:
      The connection site of modular stent grafts predisposes to stenosis, occlusion,
      and disconnection of the modular device. Stent deployment and unfolding of the
      membrane might be examined with IVUS. MRI is useful for detecting endoluminal
      deposits and stenosis. However, radiological methods will underrate
      irregularities and deposits of the endoluminal surface.

PMID- 11997858
TI  - [Bronchial artery embolization for therapy of pulmonary bleeding in patients with
      cystic fibrosis].
AB  - INTRODUCTION: Acute pulmonary emergencies in patient with cystic fibrosis (CF)
      can be found in cases of pneumothorax as well as hemoptysis. If the bleeding
      cannot be stopped by conservative methods, an embolization of the bronchial
      arteries should be done. MATERIALS AND METHOD: 11 patients were embolized using a
      combination of PVA particles and microcoils. RESULTS: From January 1996 to June
      2001 17 bronchial arteries in 11 patients were embolized. 7 patients suffered
      from chronical hemoptysis, 4 patients had an acute hemoptysis. In 4 patients both
      sides were embolized, in 3 patients only one side. The remaining 4 patients
      needed a second intervention, embolizing the other side. The primary embolizated
      bronchial artery was still closed in all 4 patients. In 1 patient the selective
      catheterization of a bronchial artery was not successful, thus the embolization
      could not be carried out. 1 patient died 5 days after the intervention due to a
      fulminant pneumonia (Pseudomonas aeruginosa) without recurrent bleeding. In two
      patients atypical branches from intercostal arteries feeding the bronchial
      arteries were detected and successfully embolized. All patients profited from the
      therapy, as bleeding could be stopped or at least be reduced. 3 patients suffered
      from back pain during or after intervention. There were no severe complications
      like neurological deficiencies or necroses. CONCLUSION: The embolization of
      bronchial arteries using particles and microcoils is an effective intervention
      with a low complication rate in pulmonary bleeding of CF patients.

PMID- 11997859
TI  - [Emergency endovascular treatment of acute aortic diseases].
AB  - PURPOSE: To investigate the safety and efficacy of emergency treatment of acute
      aortic diseases with endovascular stent grafts. METHODS: In 11 patients (median
      age 55 years, range 18 - 85) with acute complications of descending aortic
      diseases endovascular emergency treatment was performed: traumatic aortic rupture
      (n = 4), penetrating ulcer with aortobronchial fistula or hematothorax (n = 4),
      acute type B dissection (n = 2, one with penetration, one with subacute
      mesenteric ischemia), and symptomatic aneurysm of the thoracic aorta (n = 1) with
      pain and diameter progression. 15 stent grafts were implanted (Talent n = 11,
      Vanguard/Stentor n = 4). Stent extension was necessary in 4 cases. In 2 cases
      graft extension was done during the first procedure (due to distal migration and
      due to the total length of the aortic aneurysm). In 2 cases graft extension was
      performed 5 days (due to a new aortic ulcer at the proximal stent struts) and 5
      months after the initial procedure (recurrent aortobronchial fistula due to
      aneurysm progression). 14 of 15 implantations required general anesthesia, one
      symptomatic thoracic aneurysm was performed in local anesthesia and sedation.
      RESULTS: 14 of 15 graft procedures were performed using the femoral or iliac
      approach. One procedure required aortofemoral bypass grafting due to extensive
      arteriosclerotic stenosis and the stent graft was inserted via the bypass graft.
      The orifice of the subclavian artery was crossed with bare stent struts in 4
      cases without neurological complications. Median follow-up is 27 months (range 6
      to 72 months). In traumatic aortic ruptures, immediate sealing of bleeding was
      achieved and follow-up is inconspicuous at a maximum of 72 months. In cases of
      aortobronchial fistulas, follow-up is satisfactory (maximum 72 months) despite
      the necessity for reintervention and graft extension. In one acute type B
      dissection retrograde dissection of the aortic arch occurred during stent release
      with stable disease during follow-up without neurological complications. In one
      type B dissection with mesenteric ischemia the mesenteric blood flow was
      restored. A second look operation confirmed pulsatile flow in the mesenteric
      trunk but a total necrosis of the small intestine and the patient consequently
      died. CONCLUSION: Endovascular treatment is safe and effective for emergency
      treatment of life-threatening complications in selected acute aortic syndromes.
      Mid-term results are encouraging, however, regular follow-up is mandatory to
      recognize late complications of the stent graft.

PMID- 11997860
TI  - [The role of chest X-rays in the diagnosis of thoracic aortic aneurysms].
AB  - OBJECTIVE: To evaluate the role of routine chest radiographs in the diagnosis of
      thoracic aortic aneurysms (TAA). METHODS: An electronic full-text search was
      performed in our radiological information system for all patients who underwent
      chest radiograph under standard conditions between 1998 and 2000 and who had
      suspected widening or aneurysm of the thoracic aorta as a diagnosis. Computed
      tomography (CT) of the thorax was used as the gold standard and had to be
      performed within a period of 30 days. Two independent and blinded observers
      evaluated different morphologic and morphometric parameters in the diagnosis and
      correlated the results with those of CT. RESULTS: 28 patients were included in
      the present trial. With almost perfect interobserver correlation (r = 0.95) both
      investigated morphometric parameters correlated well (r = 0.85 and 0.83) with the
      diameter of the aorta as evaluated with CT. While a low subjective over-all
      probability for TAA had a negative predictive value of 100 %, we found that,
      despite an almost perfect interobserver variability (Kappa > 0.8), none of the
      investigated morphologic parameters (discrepancy between the ascending and
      descending aorta, displacement of the trachea to the right and caudal
      displacement of the left main bronchus) was significantly correlated with the
      final diagnosis. CONCLUSION: The investigated morphometric parameters help to
      estimate the diameter of the aorta in the arch and in the descending section, but
      none of the morphologic criteria can be used for the diagnosis of TAA.

PMID- 11997861
TI  - [Stress cine MRI for detection of coronary artery disease].
AB  - Stress testing is the cornerstone in the diagnosis of patients with suspected
      coronary artery disease (CAD). Stress echocardiography has become a well
      established modality for the detection of ischemia-induced wall motion
      abnormalities. However, display and reliable interpretation of stress
      echocardiography studies are user-dependent, the test reproducibility is low, and
      10 to 15 % of patients yield suboptimal or non-diagnostic images. Due to its high
      spatial and contrast resolution, MRI is known to permit an accurate determination
      of left ventricular function and wall thickness at rest. Early stress MRI studies
      provided promising results with respect to the detection of CAD. However, the
      clinical impact was limited due to long imaging time and problematic patient
      monitoring in the MRI environment. Recent technical improvements - namely
      ultrafast MR image acquisition - led to a significant reduction of imaging time
      and improved patient safety. Stress can be induced by physical exercise or
      pharmacologically by administration of a beta1-agonist (dobutamine) or
      vasodilatator (dipyridamole and adenosine). The best developed and most promising
      stress MRI technique is a high-dose dobutamine/atropine stress protocol (10, 20,
      30, 40 microgram/kg/min; optionally 0.25-mg fractions of atropine up to maximal
      dose 1 mg). Severe complications (myocardial infarction, ventricular fibrillation
      and sustained tachycardia, cardiogenic shock) may be expected in 0.25 % of
      patients. Currently, data of three high-dose dobutamine stress MRI studies are
      available, revealing a good sensitivity (83 - 87 %) and specificity (83 - 86 %)
      in the assessment of CAD. The direct comparison between echocardiography and MRI
      for the detection of stress-induced wall motion abnormalities yielded better
      results for dobutamine-MRI in terms of sensitivity (86.2 % vs. 74.3 %; p < 0.05)
      and specificity (85.7 % vs. 69.8 % p < 0.05) as compared to dobutamine stress
      echocardiography. The superior results of MRI can mainly be explained by the
      better image quality with sharp delineation of the endocardial and epicardial
      borders. Currently, stress MRI is already a realistic clinical alternative for
      the non-invasive assessment of CAD in patients with impaired image quality in
      echocardiography.

PMID- 11997862
TI  - [Stereotactic needle breast biopsy: Diagnostic reliability of various biopsy
      systems and needle sizes].
AB  - OBJECTIVES: To compare quality of harvested tissue, false-negative rate, and
      complication rate of large-core needle breast biopsy (LCNBB) and directional,
      vacuum-assisted breast biopsy (DVABB) in non-palpable breast lesions. PATIENTS
      AND METHODS: From 1994 to 1999, in 580 non-palpable breast lesions a
      stereotactically-guided breast biopsy was performed. 14-G LCNBB was used in 168
      lesions (29 %). DVABB was used in 412 lesions (71 %; 11-G DVABB: 134 lesions 32.5
      %, 14-G DVABB: 278 lesions 67.5 %). Following biopsy, patients underwent either
      surgical excision (n = 533; 93.8 %) or mammographical follow-up (n = 36; 6.2 %).
      Histological results of LCNBB, DVABB, surgical breast biopsy and follow-up
      results were compared and scored for their tissue quality on a three-point scale
      (1 = disagreement between biopsy and surgery; 2 = partial agreement; 3 = complete
      agreement). In addition, we determined the false negative and complication rate
      for both systems. RESULTS: Histological examination after surgery and follow-up
      proved 262 (45.2 %) to be benign, 15 (2.6 %) to be high-risk lesions and 303
      (52.5 %) to be malignant. In the tissue quality there was no significant
      difference between 14-G LCNBB (score = 2.94), 11-G DVABB (score = 2.92) and 14-G
      DVABB (score = 2.91) (p > 0.05). Particularly, in calcifications 11-G DVABB
      scored better (score = 2.92) than 14-G DVABB (score = 2.88) (p > 0.05). 14-G
      LCNBB had a lower false negative rate (1.8 %) than 11-G DVABB (3 %) and 14-G
      DVABB (3.2 %) (p > 0.05). There was no difference in the complication rate
      between the different needle types. CONCLUSIONS: Our results indicate that both
      LCNBB and DVABB are reliable and safe techniques in the diagnosis of non-palpable
      breast lesions. However, the use of 14-G LCNBB seems to be advantageous in
      masses, the use of 11-G DVABB seems to be advantageous in asymmetric densities
      and calcifications.

PMID- 11997863
TI  - [Do tissue marker clips after sonographically or stereotactically guided breast
      biopsy improve follow-up of small breast lesions and localisation of breast
      cancer after chemotherapy?].
AB  - PURPOSE: We wanted to determine if tissue marker clips after sonographically or
      stereotactically guided breast biopsy improve the follow-up of small breast
      lesions classified BI-RADS 4/5 and the localisation of breast cancer (TNM stage 2
      or 3) after neoadjuvant chemotherapy. MATERIAL AND METHODS: Prospective analysis
      was performed of 108 breast lesions 1 cm or smaller mammographically classified
      as BI-RADS 4/5 and 14 breast lesions larger than 2 cm mammographically classified
      as BI-RADS 5. 33 of the 108 breast lesions 1 cm or smaller underwent sonographic
      core cut breast biopsy (group 1) and 75 stereotactic vacuum-assisted breast
      biopsy (group 2). All 14 lesions greater than 2 cm were stereotactically vacuum
      assisted breast biopsied (group 3). The centre of the lesion was marked by a clip
      after the biopsy. Mammographies were performed in all patients of group 1 and 2
      with a histologically benign finding (n = 31, n = 69, respectively) and in all
      patients of group 3 directly after clip placement and after 6 and 12 months. Clip
      localisation and possible divergence from the original position were verified by
      a grid. RESULTS: Two patients of group 1 and 6 patients of group 2 had breast
      conservative surgery (BET) because of the histological diagnosis of a ductal
      carcinoma in situ or invasive breast cancer. The tissue marker clips of the
      remaining 31 patients of group 1 and 69 patients of group 2 diverged with a mean
      value of 0.4 cm (standard deviation +/- 0.23 cm; range 0.1 cm to 0.9 cm) from
      their placement position after 6 months. After 12 months the marker clips
      deviated with a mean value of 0.4 cm (standard deviation +/- 0.21 cm; range 0.1
      cm to 0.9 cm) in 94 patients and 0.8 cm (standard deviation +/- 0.25 cm; range
      0.1 cm to 0.9 cm) in 6 patients from their original location. No tumour
      progression of the benign lesions in group 1 and 2 was diagnosed in follow-up
      mammograms. In all patients of group 3 the tissue marker clips were the only
      possibility to localize the tumour after neoadjuvant chemotherapy as all other
      diagnostic methods showed inconsistent results. CONCLUSION: Positioning a tissue
      marker clip in the tumour centre seems to be reasonable after interventional
      biopsy of breast lesions of 1.0 cm or smaller and before neoadjuvant
      chemotherapy.

PMID- 11997864
TI  - [Comparison of flat-panel radiography and computed radiography in urography].
AB  - PURPOSE: To evaluate the diagnostic value of digital flat-panel radiography in
      uroradiology the i. v. urograms of patients who had been examined with computed
      radiography and digital flat-panel radiography were compared regarding image
      quality. METHODS: 50 patients who underwent clinically indicated i. v. urography
      were examined with digital flat-panel radiography and computed radiography. In
      order to avoid unnecessary double exposure to X-rays, patients were examined
      either by flat-panel or computed radiography before injection of contrast media.
      Each further clinically indicated exposure after administration of contrast media
      was done by alternating the other examination technique. The digital images were
      compared by 4 radiologists regarding image quality for the detection of defined
      anatomic structures. RESULTS: Digital flat-panel radiography showed an image
      quality of the liver, spleen and both kidneys that was similar to computed
      radiography. The urinary tract, lumbar spine, pelvis and psoas muscle were
      significantly better visible on flat-panel radiography images. CONCLUSIONS:
      Compared to computed radiography there is no loss of image information by using
      digital flat-panel radiography in uroradiology. On the contrary, some anatomic
      structures on abdominal survey images show better image quality. In conclusion,
      digital flat-panel radiography has the potential to replace computed radiography
      in uroradiologic examinations.

PMID- 11997865
TI  - [Radiation dose and image quality in computed tomography].

PMID- 11997866
TI  - [Diabetes mellitus type 2].
AB  - SUMMARY: Type 2 diabetes represents the most common form of carbohydrate
      disorders affecting at least 5% of the population in the industrialized world. In
      addition to genetic predisposition obesity and a sedentary lifestyle are the main
      promoters. Recent data clearly suggest that lifestyle intervention in people at
      increased risk can potently reduce the incidence of the disease. In overt type 2
      diabetes, good glycaemic control and aggressive management of associated
      cardiovascular risk factors may prevent its multiple and costly complications.

PMID- 11997867
TI  - [Prevalence of gastro-oesophageal reflux disease in general practice].
AB  - BACKGROUND AND OBJECTIVE: While there is an ever rising prevalence of gastro
      oesophageal reflux disease among people in the western world, the actual number
      are usually underestimated, because many afflicted persons do not seek medical
      care. This study was undertaken to determine the frequency of unrecognized reflux
      disease among an unselected patient cohort in general practice. In addition,
      answers by these patients to a questionnaire were evaluated. PATIENTS AND
      METHODS: 162 consecutive patients of a general practice without known gastro
      oesophageal reflux took part. After the questionnaire had been filled in a
      history was obtained with semi-quantitative grading of dyspeptic symptoms, and
      all underwent a physical examination. A gastroscopy was offered to all patients.
      Gastro-oesophageal reflux was diagnosed when endoscopy revealed typical
      oesophageal lesions and/or there were at least moderately severe reflux symptoms
      that had reduced the patient's quality of life. RESULTS: 82 patients (51%) had
      reflux disease. 121 patients underwent endoscopy. Structural changes (reflux
      oesophagitis, Barrett metaplasia) were seen in 28 of the 82 patients with reflux
      disease (34%), 17% of the entire cohort. Axial hiatus hernia, positive family
      history, advancing age, over-weight, female gender and treatment with NSAIDs or
      aspirin were significant risk factors in the development of reflux disease.
      Patients with reflux disease significantly more frequently suffered from
      hoarseness and/or cough. Positive or negative predictability of the questionnaire
      regarding the diagnosis of reflux disease was 94% each way. CONCLUSION: The
      prevalence of unrecognized gastro-oesophageal reflux disease in the population is
      extraordinarily high. One quarter to one third of those with reflux disease have
      cough or hoarseness. The disease can apparently be reliably diagnosed by a
      standardized questionnaire.

PMID- 11997868
TI  - [Primary hypertrophic osteoarthropathy (Touraine-Solente-Gole syndrome)].
AB  - HISTORY: A 29-year-old man had finger clubbing since the age of 15 years, and for
      the last 10 years his hands and feet had grown disproportionately. In addition he
      suffered from marked whole-body sweating, especially of the hands and feet, as
      well as persistent pain in the limbs and joints. INVESTIGATIONS: Biochemical and
      endocrinological tests were normal. Radiology of the hands and lower legs
      revealed marked periosteal thickening, while the substantia trabeculosa was
      unremarkable. Secondary causes having been excluded primary hypertrophic
      osteoarthropathy was diagnosed. TREATMENT AND COURSE: While there is no causal
      treatment, physio- and balneotherapy improved the symptoms. CONCLUSION: Early and
      accurate diagnosis of primary hypertrophic osteoarthropathy is essential, if only
      because of its favourable long-term prognosis.

PMID- 11997869
TI  - [Adverse drug reactions--case report].

PMID- 11997870
TI  - [Adverse drug reactions. QT-prolongation and torsade-de-pointes arrhythmias].

PMID- 11997871
TI  - [Adverse drug reactions. Hereditary differences in drug metabolism].

PMID- 11997874
TI  - [Acute pancreatitis. Recent aspects of diagnosis and therapy].

PMID- 11997875
TI  - [Prevention and treatment in the elderly. 2002 recommendations of the National
      Heart-Circulation Conference].

PMID- 11997876
TI  - [Immunopathogenesis of atherosclerosis. The Mainz hypothesis].

PMID- 11997877
TI  - Changing distribution of monoaminergic markers in the developing human cerebral
      cortex with special emphasis on the serotonin transporter.
AB  - This article reviews the current knowledge of the early onset of the
      monoaminergic innervation in the developing cerebral cortex in humans and of
      changes in the distribution of tyrosine hydroxylase (TH) immunoreactivity in
      different neuronal populations of the developing telencephalon. The early genesis
      of the central monoaminergic neurons in mammals has led to postulations of a
      trophic role of monoamines in brain morphogenesis--especially in the cerebral
      cortex. The developmental effects of amines can be linked to the transient
      expression of different molecules linked to dopamine or serotonin
      neurotransmission. We present novel data on the immunocytochemistry of the
      vesicular monoamine transporter (VMAT2) and of the high-affinity serotonin
      transporter (SERT) in human fetuses. SERT is a marker of the serotoninergic axons
      and allows visualization of the serotonin afferents of the raphe in the human
      telencephalon. In addition, during a restricted time period corresponding to 12
      14 postovulatory weeks, we found SERT-immunolabeled fibers in the rostral and
      caudal limbs of the internal capsule that do not correspond to serotoninergic
      fibers, but do coincide with the calbindin D28k-labeled thalamocortical fiber
      tracts. The present observations are correlated with findings in rodents, in
      which a transient expression of SERT is visible in the thalamocortical axons
      during early postnatal life. The function of this transporter has been shown to
      be important for the fine-tuning of cortical sensory maps during the critical
      period of development of these maps. Although the present observation does not
      allow ascertainment of which neurons transiently express SERT, it lends support
      to the notion that serotonin and serotonin uptake could have important
      developmental roles, during the formation of brain connections in humans, as they
      have in rodents.

PMID- 11997878
TI  - Kidney of giraffes.
AB  - This study focuses on certain aspects of the renal structure of the giraffe, with
      some implications as to its function. About 4,000 collecting ducts open at the
      truncated end of a curved crest that juts into the renal pelvis as the inner
      medulla (IM). Extensions of the pelvis pass between the medullary (MP) and
      vascular (VP) processes almost to the corticomedullary border. The MPs contain an
      IM and an outer medulla (OM) containing clusters of capillaries (vascular
      bundles). The VPs contain the interlobar arteries and veins. All of the IM and
      almost all of the OM, with its vascular bundles, are bathed with pelvic urine.
      The cortex comprises 63% of the parenchyma. The OM has nine times the mass of the
      IM. The IM comprises 4% of the parenchyma. The ratio of mass of the adult cortex
      to the medulla is 1.7:1.0, and the number of glomeruli per kidney is 6.6 x 10(6).
      Glomerular mass is 6.2-6.7% of renal mass in the adult and 5.2% in the 6-month
      old calf. The dimensions of the glomerular capsules are the same across the
      thickness of the cortex. Every terminal collecting duct drains an estimated 1,650
      nephrons. In the adult giraffe the ratio of thickness of the muscularis of the
      main renal artery (RA) to its diameter is 0.117 (right RA) and 0.132 (left RA).
      These ratios are close to those in rhinoceros and ox but greater than in man. The
      visceral arteries (celiac, anterior mesenteric, and renal) have about the same
      muscularis : diameter ratio. Giraffes have arterial hypertension, but
      atherosclerosis is apparently absent and serum lipid fractions are low.

PMID- 11997879
TI  - Acetylcholine receptors and nerve terminal distribution at the neuromuscular
      junction of non-obese diabetic mice.
AB  - Skeletal muscle is one of the main targets of the metabolic alterations in
      diabetes, in which protein synthesis is markedly reduced followed by increased
      proteolysis. Ultrastructural and functional changes in the presynaptic
      compartment of the neuromuscular junction (NMJ) have been demonstrated, but
      little attention has been paid to the proteins in the postsynaptic muscle fiber
      membrane. In the present work, we studied the changes in acetylcholine receptors
      (AChRs) and nerve terminal distribution in the NMJ of non-obese diabetic (NOD)
      mice. The sternomastoid muscles of adult female NOD mice were double-labeled for
      AChR and nerve terminal observation by fluorescence and reflected light confocal
      microscopy. In 62.4% of the diabetic endplates, AChR branches broke apart into
      receptor islands that stained less than in the normal mice. These patches had
      regular junctional folds. At most of the endplates studied, the nerve terminals
      colocalized with AChRs, and sprouts were seen in 10% of the diabetic endplates.
      The intramuscular nerve branches and axons in the nerve to the sternomastoid
      muscle showed no degenerative disorders. These results suggest that metabolic
      alterations in the diabetic muscle fiber can affect the distribution and
      expression of molecules, such as AChRs, in the postsynaptic membrane of the
      neuromuscular junction.

PMID- 11997880
TI  - Transforming growth factor-beta 3(Tgf-beta3) in a collagen gel delays fusion of
      the rat posterior interfrontal suture in vivo.
AB  - Postnatal expansion of the intramembranous bones of the craniofacial skeleton
      occurs as bone growth at sutures. Loss of the bone growth site occurs when the
      suture fails to form, or when the newly formed sutures become ossified, resulting
      in premature obliteration. Previous experiments demonstrated that removal of dura
      mater from fetal rat coronal sutures, or neutralizing transforming growth factor
      beta 2 (Tgf-beta2) activity using antibodies resulted in premature obliteration
      of the suture in vitro. Conversely, addition of Tgf-beta3 to coronal sutures in
      vitro rescued them from osseous obliteration. To examine whether Tgf-beta3
      rescues sutures from obliteration in vivo, a collagen gel was used as a vehicle
      to deliver Tgf-beta3 to the normally fusing rat posterior interfrontal (IF)
      suture. Surgery was done on postnatal day 9 (P9) rats, in which collagen gels
      containing 0, 3, or 30 ng Tgf-beta3 were placed above the IF suture, underneath
      the periosteum for 2 weeks. By P24, 75-100% of animals in control unoperated,
      sham-operated, and collagen gel-only groups had fused IF sutures. In contrast,
      40% of sutures exposed to 3 ng Tgf-beta3 remained open, while sutures exposed to
      30 ng Tgf-beta were similar to controls. By immunohistochemistry, sutures rescued
      from obliteration by Tgf-beta3 had the same Tgf-beta receptor type II (Tbetar-II)
      distribution as controls. However, Tgf-beta3-treated sutures had altered Tgf
      beta2 and Tbetar-I distribution compared to controls.

PMID- 11997881
TI  - Spatial relation between major histocompatibility complex-restricted antigen
      receptor-bearing thymocytes and subtypes of thymic epithelial cells.
AB  - R73, a monoclonal antibody that recognizes a rat T cell surface antigen of
      TCR(alphabeta), was used to identify thymocytes that express major
      histocompatibility complex-restricted antigen receptors, and to define the
      spatial relation between these receptor-bearing thymocytes and individual thymic
      cortical and medullary epithelial subtypes by ultrastructural
      immunohistochemistry. We show that in both the cortex and medulla 1) the
      thymocytes that reacted with R73 antibodies exhibited three staining patterns:
      cytoplasmic-only staining, simultaneous cytoplasmic and surface membrane
      staining, and surface membrane-only staining; 2) the subcapsular/perivascular
      epithelial cells (ECs) were usually associated with thymocytes expressing
      perinuclear staining only; and 3) the surface membrane areas of thymocytes that
      expressed antigen receptors made contact with pale and intermediate ECs, but not
      with dark cells. These results suggest that thymic selection of major
      histocompatibility complex restriction and/or tolerance may occur by interaction
      of the receptors on maturing thymocytes with major histocompatibility complex
      antigens on thymic ECs in general, and on pale and intermediate subtypes in
      particular.

PMID- 11997882
TI  - Cellular changes in experimental left heart hypoplasia.
AB  - Hypoplastic left heart syndrome (HLHS) is a rare but deadly congenital
      malformation, which can be created experimentally in the chick embryo by left
      atrial ligation (LAL). The goal of this study was to examine the cellular changes
      leading to the profound remodeling of ventricular myocardial architecture that
      occurs in this model. Hypoplasia of left heart structures was produced after 3H
      thymidine prelabeling by partial LAL at stage 24, thereby reducing its volume,
      and redistributing blood preferentially to the developing right ventricle (RV).
      Controls included both sham-operated and intact stage-matched embryos. Survivors
      were studied 4 days after the ligation, when the heart organogenesis was
      essentially complete. Paraffin sections of the hearts were subjected to
      autoradiography and immunohistochemistry to detect changes in history of cell
      proliferation and expression of myosin, and growth factors implicated in
      cardiomyocyte proliferation. Sampling for apoptosis detection using TUNEL assay
      was done at stages 29 and 34. LAL resulted in decreased levels of proliferation
      in the left ventricular compact layer and trabeculae. The right ventricular
      compact layer also showed a slight decrease, but the trabeculae showed no
      differences. Anti-myosin staining was significantly reduced in all compartments.
      The expression levels of growth factors were altered as well. Apoptosis was
      increased in the right atrioventricular mesenchyme, with no changes in the
      working myocardium. These data suggest that changes in cardiomyocyte
      proliferation play a significant role in the pathogenesis of HLHS.

PMID- 11997883
TI  - Scanning electron microscopy study of the tongue and lingual papillae of the
      California sea lion (Zalophus californianus californianus).
AB  - We observed the three-dimensional structures on the external surface and the
      connective tissue cores (CTCs) of the California sea lion (Zalophus californianus
      californianus), after exfoliation of the epithelium of the lingual papillae
      (filiform, fungiform, and vallate papillae), using scanning electron microscopy
      (SEM) and conventional light microscopy. Macroscopically, the tongue was V-shaped
      and its apex was rounded. At the posterior area of the tongue, five vallate
      papillae were arranged in a V shape. In the epithelium, numerous taste buds were
      distributed on the top of the vallate papillae. On the dorsal surface from the
      apex to the boundary between the anterior and posterior tongue, filiform papillae
      were densely distributed. The CTCs of the filiform papillae consisted of a main
      protrusion (primary core) and many small cores (secondary cores). From the apex
      to the anterior one-third of the tongue, dome-like fungiform papillae were
      densely distributed, whereas fewer were located at the posterior two-thirds of
      the tongue. Several taste buds were found in the epithelium on the fungiform
      papillae. The size of the filiform papillae gradually increased from the apex to
      the boundary between the anterior and posterior tongue. At the lingual radix, the
      conical papillae, which were bigger than any filiform papillae, were densely
      distributed. The morphological characteristics of the tongue of the California
      sea lion appear to have been transformed to adapt to an aquatic environment;
      however, they possess some structures similar to those of land mammals.

PMID- 11997884
TI  - Circumferential variation in human second metacarpal cortical thickness: sex,
      age, and mechanical factors.
AB  - Variation in cortical thickness (CT) in four quadrants of the human second
      metacarpal was investigated in a sample (100 males and 72 females, skeletal age
      20 to 50+ years) from a 19th-century cemetery. Both left and right elements were
      studied (total N = 344). Multivariate analysis of covariance (MANCOVA) (for age,
      sex, and side, controlling for absolute size) was used to test the hypothesis of
      equality of thickness in the dorsal, palmar, medial, and lateral quadrants.
      Differences in regional CT posits localized regulation of resorption and
      formation adapting bone shape to functional loads, with implications for activity
      modulation of skeletal senescence. The palmar cortex was found to be uniformly
      thicker in both sexes and both sides, and at all ages (young, middle, and old
      adult); the medial, lateral, and dorsal cortices did not differ significantly.
      Patterns of age-related loss occurring preferentially at the endocortical surface
      differed between men and women, with women showing significant declines across
      all age groups for all quadrants, and males only small decrements after middle
      age. The greater CT in the palmar quadrant corresponds to the region of maximum
      compressive strain in the second metacarpal for functions involving full flexion
      (grasping). Although the palmar cortex is thicker at all ages, women lose mass in
      that quadrant at the same rate as in other quadrants, suggesting that function
      does not offer protection against endocrinologically-mediated depletion of bone
      mass (postmenopausal osteopenia).

PMID- 11997885
TI  - Role of the gubernacular bulb in cremaster muscle development of the rat.
AB  - The role of the gubernaculum during the inguino-scrotal phase of testicular
      descent remains controversial. Some authors propose involution and eversion while
      others suggest active migration, although the site of growth is unknown. We aimed
      to determine whether the gubernacular bulb is actively proliferating or
      regressing during inguino-scrotal testicular descent in the rat. Gubernacula were
      removed from Sprague-Dawley rats and congenitally-cryptorchid TS mutant rats.
      Animals (0, 3, 7, 10, and 11 days of age) were treated with bromodeoxyuridine
      (BUdR) 2 hr before they were killed. BUdR incorporation into newly synthesized
      DNA served as a marker of cell division. The gubernacula were histologically
      processed for hematoxylin-eosin (H&E) and immunoperoxidase staining. Four
      different areas within the gubernaculum were examined for BUdR-positive cells:
      area 1: plica gubernaculi (cord); area 2: pars infravaginalis gubernaculi (bulb);
      area 3: distal part of the cremaster muscle; and area 4: proximal part of the
      cremaster muscle. The rate of cell division for each of these areas was
      determined by counting the number of BUdR-positive cells per 100 cells. The
      highest rate of BUdR labeling in both types of rats was in area 2, which is the
      tip of the gubernacular bulb, and this was significantly greater (P < 0.0001)
      than in the gubernacular cord or developing cremaster muscle. The mitotic
      activity was also noted to be significantly greater (P < 0.0001) at the distal
      end of the cremaster muscle than at the proximal end. The amount of mitosis
      decreased significantly (P < 0.01) in areas 2 and 4 of the gubernaculum in
      Sprague-Dawley rats across the period studied. This trend was not observed in TS
      rats. Our results suggest that the bulb actively proliferates after birth, with
      possible differentiation into new cremaster muscle cells. We propose that the
      bulb is the growing end of the elongating gubernaculum, analogous to the growth
      of a limb bud.

PMID- 11997886
TI  - Histological definition of the vomeronasal organ in humans and chimpanzees, with
      a comparison to other primates.
AB  - The vomeronasal organ (VNO) is a chemosensory structure that has morphological
      indications of functionality in strepsirhine and New World primates examined to
      date. In these species, it is thought to mediate certain socio-sexual behaviors.
      The functionality and even existence of the VNO in Old World primates has been
      debated. Most modern texts state that the VNO is absent in Old World monkeys,
      apes, and humans. A recent study on the VNO in the chimpanzee (Smith et al.,
      2001b) challenged this notion, demonstrating the need for further comparative
      studies of primates. In particular, there is a need to establish how the
      human/chimpanzee VNO differs from that of other primates and even nonhomologous
      mucosal ducts. Histochemical and microscopic morphological characteristics of the
      VNO and nasopalatine duct (NPD) were examined in 51 peri- and postnatal primates,
      including humans, chimpanzees, five species of New World monkeys, and seven
      strepsirhine species. The nasal septum was removed from each primate and
      histologically processed for coronal sectioning. Selected anteroposterior
      intervals of the VNO were variously stained with alcian blue (AB)-periodic acid
      Schiff (PAS), PAS only, Gomori trichrome, or hematoxylin-eosin procedures. All
      strepsirhine species had well developed VNOs, with a prominent neuroepithelium
      and vomeronasal cartilages that nearly surrounded the VNO. New World monkeys had
      variable amounts of neuroepithelia, whereas Pan troglodytes and Homo sapiens had
      no recognizable neuroepithelium or vomeronasal nerves (VNNs). Certain
      unidentified cell types of the human/chimpanzee VNO require further examination
      (immunohistochemical and electron microscopic). The VNOs of P. troglodytes, H.
      sapiens, and New World monkeys exhibited different histochemistry of mucins
      compared to strepsirhine species. The nasopalatine region showed great variation
      among species. It is a blind-ended pit in P. troglodytes, a glandular recess in
      H. sapiens, a mucous-producing duct in Otolemur crassicaudatus, and a stratified
      squamous passageway in all other species. This study also revealed remarkable
      morphological/histochemical variability in the VNO and nasopalatine regions among
      the primate species examined. The VNOs of humans and chimpanzees had some
      structural similarities to nonhomologous ciliated gland ducts seen in other
      primates. However, certain distinctions from the VNOs of other primates or
      nonhomologous epithelial structures characterize the human/chimpanzee VNO: 1)
      bilateral epithelial tubes; 2) a superiorly displaced position in the same plane
      as the paraseptal cartilages; 3) a homogeneous, pseudostratified columnar
      morphology with ciliated regions; and 4) mucous-producing structures in the
      epithelium itself.

PMID- 11997887
TI  - Comparative study of the innervation patterns of the hyobranchial musculature in
      three iguanian lizards: Sceloporus undulatus, Pseudotrapelus sinaitus, and
      Chamaeleo jacksonii.
AB  - The neuroanatomy and musculature of the hyobranchial system was studied in three
      species of iguanian lizards: Sceloporus undulatus, Pseudotrapelus sinaitus, and
      Chamaeleo jacksonii. The goal of this study was to describe and compare the
      innervation and arrangement of the hyobranchial musculature in the context of its
      function during tongue protrusion. A comparison of the hyobranchial innervation
      patterns revealed a relatively conserved innervation pattern in S. undulatus and
      P. sinaitus, and a modified version of this basic layout in C. jacksonii. All
      three species show anastomoses between sensory neurons of the trigeminal nerve
      and motor neurons of the hypoglossal nerve, suggesting that feedback may be
      important in coordinating tongue, jaw, and hyoid movements. The hyobranchial
      musculature of S. undulatus is very similar to that of P. sinaitus; however,
      there are minor differences, including the presence of an M. genioglossus
      internus (GGI) muscle in S. undulatus. Further differences are found mainly in
      functional aspects of the hyobranchial musculature, such as changes in the muscle
      lengths and the origins and insertions of the muscles. In C. jacksonii the
      hyobranchial system is comprised of largely the same components, but it has
      become highly modified compared to the other two species. Based on the
      innervation and morphological data gathered here, we propose a revision of the
      terminology for the hyobranchial musculature in iguanian lizards.

PMID- 11997889
TI  - Role of magnetic resonance imaging in the diagnosis and monitoring of multiple
      sclerosis: consensus report of the White Matter Study Group.
AB  - On June 24-26, 2001, the first meeting of the White Matter Study Group (WMSG) of
      the International Society for Magnetic Resonance in Medicine (ISMRM) was held in
      Bordeaux, France. This paper is the report of the consensus reached among the
      delegates of the meeting on how to use magnetic resonance imaging (MRI) to make
      an early diagnosis of multiple sclerosis (MS), to measure MS activity accurately
      and reliably, and to monitor the effect of treatment on disease evolution.

PMID- 11997890
TI  - Magnetic resonance image registration in multiple sclerosis: comparison with
      repositioning error and observer-based variability.
AB  - PURPOSE: To study the use of image registration in the analysis of multiple
      sclerosis (MS) lesion volume and compare this with repositioning error and
      observer-based variability. MATERIALS AND METHODS: The normalized mutual
      information (NMI) algorithm is evaluated in an accuracy study using a phantom,
      followed by a validation study on magnetic resonance (MR) data of MS patients.
      Further, using scan-rescan MR data, the effect of registration on MS lesion
      volume compared with repositioning error and observer-based variability is
      assessed. RESULTS: The registration accuracy was near perfect in the phantom
      study, while the in vivo validation study demonstrated an accuracy on the order
      of 0.2-0.3 mm. In the scan-rescan study, quantification accounted for 15.6% of
      the relative variance, repositioning for 44.4%, and registration for 40.0%.
      CONCLUSION: NMI resulted in robust and accurate alignment of MR brain images of
      MS patients. Its use in the detection of changes in MS using large serial MR
      imaging (MRI) data warrants future evaluation.

PMID- 11997891
TI  - MR perfusion, diffusion and BOLD imaging of methotrexate-exposed swine brain.
AB  - PURPOSE: To evaluate the methotrexate (MTX)-exposed swine brain, functional
      magnetic resonance imaging (MRI), including perfusion, diffusion, and blood
      oxygen-level-dependent (BOLD) contrast imaging, was used. MATERIAL AND METHODS:
      Juvenile pigs received either 2 x 5 g/m(2), or 5 x 2 g/m(2) MTX intravenously
      within one month. MRI was performed (sedative: propofol) before (14-17 kg, N = 6)
      and after (21-27 kg, N = 4) the MTX exposure. Also, age-matched controls (22-27
      kg, N = 4) were imaged. RESULTS: After the MTX exposure, reduced (from 2%-4% to
      0%-1%) or negative (-2% to -3%) BOLD responses were detected; apparent diffusion
      coefficient (ADC) or relative perfusion values did not change. CONCLUSION: This
      study suggests that MTX-related changes in the brain may be detected as changes
      in flow-metabolism coupling as reduced or negative response (for somatosensory
      activation) in the BOLD contrast MRI. The contrast agent perfusion MRI, without
      absolute quantification, may not show global damage in brain perfusion related to
      the MTX exposure in the swine model used. ADC (in one direction) may not indicate
      MTX-related changes in the brain.

PMID- 11997892
TI  - Comparison of the threshold for peripheral nerve stimulation during gradient
      switching in whole body MR systems.
AB  - PURPOSE: To compare thresholds for peripheral nerve stimulation from gradient
      switching in whole body magnetic resonance (MR) equipment of different design.
      MATERIALS AND METHODS: Threshold data obtained in three experiments were
      reformatted into a single joint data set describing thresholds for anterio
      posterior (AP) gradient orientation and Echo Planar Imaging (EPI) waveforms with
      bipolar ramp times between 0.07 and 1.2 ms. Reformatting included the use of: a)
      the rate of change of the maximum field in the patient space as a measure of
      gradient output, b) lowest observable thresholds, c) lognormal distribution of
      thresholds, and d) equal standard deviation (SD) of all samples. RESULTS: The
      joint data fit a hyperbolic threshold function. The residues were not
      significantly different between experiments. CONCLUSION: Then expressed in
      appropriate format, the thresholds for peripheral nerve stimulation in volunteers
      for whole body MR equipment can be described with a hyperbolic threshold curve
      with rheobase 18.8 +/- 0.6 Tesla/second and chronaxie 0.36 +/- 0.02 milliseconds.

PMID- 11997893
TI  - TrueFISP: assessment of accuracy for measurement of left ventricular mass in an
      animal model.
AB  - PURPOSE: To test the accuracy of a high performance true fast imaging with steady
      state precession (TrueFISP) pulse sequence for the assessment of left ventricular
      (LV) mass in a large animal model on 1.5-T scanners. MATERIALS AND METHODS: We
      imaged dogs (N = 10) on a clinical 1.5-T clinical scanner using electrocardiogram
      (ECG)-gated TrueFISP. In all animals, contiguous segmented k-space cine images
      were acquired from base to apex (in-plane resolution 1 x 1 mm(2), slice thickness
      5 mm, TR = 4.8 msec, TE = 1.6 msec) during repeated breath-holds. In nine of the
      10 animals, single-shot images gated to end-diastole were also acquired from base
      to apex in a single breath-hold (in-plane resolution 1 x 1 mm(2), slice thickness
      5 mm, TR = 3.2 msec, TE = 1.6 msec). After imaging, animals were killed, the left
      ventricle was isolated, and the true mass of the left ventricle (free wall and
      septum) was determined. Independently, two observers blinded to the post-mortem
      results computed LV masses based on analysis of the magnetic resonance (MR)
      images. RESULTS: Comparison of the computed LV mass using TrueFISP to the actual
      mass showed excellent agreement. Cine-systole was the most accurate technique
      (mass = 98.6% +/- 4.5% actual, bias = 1.2 +/- 3.4 g) followed by cine-diastole
      (mass = 97.9% +/- 5.3% actual, bias = 1.8 +/- 4.1 g) and single shot (mass =
      94.7% +/- 7.9% actual, bias = 4.2 +/- 6.3 g). Inter- and intra-observer
      variabilities were low (5.8% +/- 7.1% and 0.4% +/- 4.8%, respectively).
      CONCLUSION: We conclude that TrueFISP imaging is an accurate, rapid method to
      determine ventricular mass. In single-shot mode, TrueFISP requires only one
      breath-hold to estimate the mass of the heart within 6% of the actual value,
      whereas the segmented k-space implementation measured LV mass to within 3% of the
      true value.

PMID- 11997894
TI  - Simultaneously monitoring both T(1) and T(2)* signal intensities on a bolus
      injection of Gd-DTPA may distinguish infarcted myocardium.
AB  - PURPOSE: To determine whether injured myocardium may be identified by
      simultaneously monitoring contrast-induced T(1) and T(2)* signal intensity time
      course changes with an interleaved T(1)-T(2)* imaging sequence. MATERIALS AND
      METHODS: Gadolinium-diethylene triamine pentaacetic acid (0.05 mmol/ kg) was
      injected as a bolus into ex vivo pig hearts, and simultaneous T(1) and T(2)* time
      courses were obtained during the first pass. RESULTS: Observing contrast-enhanced
      R(1) or R(2)* rates (1/T(1) or 1/T(2)* times, respectively) early after contrast
      injection did not fully differentiate viable from nonviable myocardium. T(2)*
      recovery at maximal T(1) signal intensity, measured using simultaneous T(1) and
      T(2)* imaging, displayed a significantly different percentage recovery (P < 0.05)
      among normal (30.5 +/- 2.4% of baseline value), reperfused infarcted (63 +/-
      7.2%), and low-reflow infarcted (90 +/- 2.8%) myocardium. CONCLUSION:
      Simultaneously monitoring both T(1) and T(2)* signal intensities may help in the
      assessment of myocardial injury.

PMID- 11997895
TI  - Analysis of subtraction methods in three-dimensional contrast-enhanced peripheral
      MR angiography.
AB  - PURPOSE: To compare the effectiveness of three image subtraction algorithms
      designed to improve arterial conspicuity in first-pass contrast-enhanced magnetic
      resonance (MR) angiography. MATERIALS AND METHODS: Three subtraction methods were
      analyzed through computer simulations, phantom studies, and clinical studies.
      These algorithms were: complex subtraction, magnitude subtraction, and maximum
      intensity projection subtraction. RESULTS: In high resolution three-dimensional
      imaging, maximum intensity projection subtraction generally yields the best
      background suppression. Complex subtraction is effective in reducing partial
      volume effects in low resolution imaging. Magnitude subtraction works better in
      high resolution, low contrast concentration protocols. CONCLUSION: Choosing the
      appropriate subtraction method according to the protocol is helpful in optimizing
      image quality.

PMID- 11997896
TI  - Ovarian veins: magnetic resonance imaging findings in an asymptomatic population.
AB  - PURPOSE: To evaluate the magnetic resonance (MR) venographic appearance of the
      ovarian veins in a healthy population, correlated with surgical findings. Our
      data can be used as a basis for comparison to patients with suspected pelvic
      congestion syndrome (PCS). MATERIALS AND METHODS: We retrospectively reviewed
      exams of 22 women who had MR angiography for potential renal donation evaluation
      (age range, 19.3-60.5 years; mean, 38 years). We evaluated the diameter of the
      ovarian veins on dynamic multiphasic postcontrast coronal images, the phase of
      contrast appearance in these veins, the apparent direction of flow, and the
      presence of ovarian or pelvic varices. Surgical correlation was obtained in 12
      patients. Clinical charts were reviewed and patients were asked about symptoms of
      chronic pelvic pain and the number of their children. RESULTS: Of the 22 exams,
      21 left gonadal veins were identified. Passive reflux from the left renal vein
      into the left gonadal vein was suggested in eight exams (38%). These veins had a
      mean diameter of 6.4 +/- 1.6 mm, significantly larger than 4.5 +/- 1.3 mm for the
      other 13 left gonadal veins without reflux (P < 0.005). The right gonadal vein
      was identified in 8 of 22 women, with a mean diameter of 4.4 +/- 0.5 mm. No
      patient reported symptoms of chronic pelvic pain. CONCLUSION: Passive reflux from
      the left renal vein to the left gonadal vein can occur in asymptomatic women.
      Diagnosis of PCS depends heavily on appropriate clinical history.

PMID- 11997897
TI  - Comparison of two volumetric techniques for estimating liver volume using
      magnetic resonance imaging.
AB  - PURPOSE: To compare the conventional technique of manual planimetry with the
      point counting technique for estimating liver volume from magnetic resonance
      imaging (MRI) data. MATERIALS AND METHODS: This study comprised abdominal MR
      examinations of 38 consecutive patients. Evaluation of the images showed that
      liver size appeared normal in 27 patients and increased in 11. Liver volume was
      estimated using the techniques of planimetry and point counting. Both techniques
      were used in combination with the Cavalieri method of modern design stereology. A
      systematic slice sampling procedure was performed to estimate liver volumes using
      both volumetric techniques. The point counting technique was optimized by
      altering the point spacing of the grid. The agreement between the two techniques
      was found. Measurement repeatability of both volumetric techniques was also
      evaluated. RESULTS: Both techniques allowed the same degree of optimization
      through the procedure of systematic section sampling. The application of a point
      spacing of 2.5 cm reduced the time measurement by a factor of 3.5 in relation
      with the time needed with planimetry. An excellent agreement was observed between
      the two volumetric techniques with mean differences (+/-SD) of 2.4 +/- 41.6 cm(3)
      and 8.5 +/- 49.8 cm(3) for the patients presenting normal and increased liver
      sizes, respectively. Both techniques were highly reproducible. CONCLUSION: The
      point counting technique could be considered a more efficient approach than
      planimetry for estimating liver volume from MRI, due to its speed and simplicity.

PMID- 11997898
TI  - Evaluation of hepatic lesions and hepatic parenchyma using diffusion-weighted
      reordered turboFLASH magnetic resonance images.
AB  - PURPOSE: To determine whether the centric reordered snapshot fast low-angle shot
      (reordered turboFLASH) magnetic resonance (MR) images with no, low, and high
      motion-probing gradients (MPGs) were useful to evaluate hepatic lesions and
      hepatic parenchyma. MATERIALS AND METHODS: The measured diffusion coefficient
      (D), deviation factor (f), and apparent diffusion coefficient for flowing spin
      (D*) values for 92 hepatic lesions (33 hepatocellular carcinomas (HCCs), 17
      metastases, 27 hemangiomas, and 15 cysts) and the nonlesion-bearing regions of
      parenchyma in 74 livers (46 noncirrhotic and 28 cirrhotic) were approximately
      calculated from the reordered turboFLASH images (modified for diffusion
      sensitivities of b = 0, 50.2, and 295 seconds/mm(2)). RESULTS: These groups,
      listed in order of decreasing D* and f values, were cysts, noncirrhotic livers,
      cirrhotic livers, hemangiomas, metastases, and HCCs. The order on the basis of D
      values was cysts, hemangiomas, metastases, HCCs, cirrhotic livers, and
      noncirrhotic livers. Noncirrhotic livers showed higher D* and f values, and lower
      D values than HCCs and metastases (P < 0.04). CONCLUSION: The D* and f values, in
      addition to the D value, may be useful for evaluating the nature of diffusion and
      flowing spins in hepatic lesions and hepatic parenchyma.

PMID- 11997899
TI  - Characterization of focal hepatic lesions with ferumoxides-enhanced MR imaging:
      utility of T1-weighted spoiled gradient recalled echo images using different echo
      times.
AB  - PURPOSE: To evaluate the different signal characteristics of focal hepatic
      lesions on ferumoxides-enhanced MR imaging, including T1-weighted spoiled
      gradient recalled echo (GRE) images using different echo times (TE) and T2- and
      T2*-weighted images. MATERIALS AND METHODS: Ferumoxides-enhanced MR imaging was
      performed using a 1.5-T system in 46 patients who were referred for evaluation of
      known or suspected hepatic malignancies. One hundred and seven lesions (42
      hepatocellular carcinomas [HCC], 40 metastases, 13 cysts, eight hemangiomas,
      three focal nodular hyperplasias [FNHs], and one cholangiocarcinoma) were
      evaluated. Postcontrast MR imaging included 1) T2-weighted FSE; 2) T2*-weighted
      GRE; 3) T1-weighted spoiled GRE using moderate (TE = 4.2-4.4 msec) TE; and 4)
      minimum (TE = 1.8-2.1 msec) TE. Signal intensities of the focal lesions were
      rated by two radiologists in conference as follows: hypointense, isointense or
      invisible, hyperintense, and markedly hyperintense. Lesion-to-liver contrast-to
      noise ratio (C/N) was measured by one radiologist for a quantitative assessment.
      RESULTS: On ferumoxides-enhanced FSE images, 92% of cysts were "markedly
      hyperintense" and most of the other lesions were "hyperintense", and the mean C/N
      of cysts was significantly higher than that of other focal lesions. T2*-weighted
      GRE images showed most lesions with similar hyperintensities and the mean C/N was
      not significantly different between any two types of lesion. T1-weighted GRE
      images using moderate TE showed all FNHsand hemangiomas, 29 (69%) HCCs and eight
      (20%) metastases as "hyperintense". On T1-weighted GRE images using minimum TE,
      however, all HCCs and metastasis except one were iso- or hypointense, while all
      of the FNHs and hemangiomas were hyperintense. Ring enhancement was highly
      suggestive of malignant lesions, and was more commonly seen on the minimum TE
      images than on the moderate TE images. CONCLUSION: Addition of T1-weighted GRE
      images using minimum and moderate TE is helpful for characterizing focal lesions
      in ferumoxides-enhanced MR imaging.

PMID- 11997900
TI  - Biological dosimetry of magnetic resonance imaging.
AB  - PURPOSE: To check the bioeffects of the components of magnetic resonance imaging
      (MRI). MRI is based on an assumed harmless interaction between certain nuclei in
      the body when placed in a strong magnetic field and radio wave fields. There are
      three key factors actuating on the examining body: a powerful static magnetic
      field (SMF), magnetic gradient fields (MGFs), and pulsed radiofrequency (RF)
      radiation. MATERIALS AND METHODS: In vitro cells (L-132 cells) were used as
      biosensors, and different cellular compounds were used as biomarkers (heat shock
      proteins [HSPs] and their messenger ribonucleic acids [mRNAs], calcium, and
      adenosine-3',5'-cyclic monophosphate [cAMP]). The biosensors were placed in the
      bore of a 1.5-T MRI machine and the different electromagnetic fields were
      operated. RESULTS: HSPs and their mRNAs and cAMP did not respond to SMF, MGFs, or
      RF radiation. RF radiation increased cytosolic calcium concentration (18%, P <
      0.05). CONCLUSION: Although MRI procedures do not induce any cellular stress
      response, it may cause an unfathomable calcium increase in vitro. Although the in
      vitro experimental conditions are not totally comparable to clinical situations,
      the usefulness of the in vivo biological dosimetry, circulating leukocytes as
      biosensors, and HSPs and/or calcium as biomarkers is suggested.

PMID- 11997901
TI  - Effect of b value on contrast during diffusion-weighted magnetic resonance
      imaging assessment of acute ischemic stroke.
AB  - PURPOSE: To examine the effect of varying the diffusion encoding strength (b
      value) on the contrast (signal difference, Delta S) between damaged and normal
      tissue during diffusion-weighted magnetic resonance imaging (DWI) assessment of
      acute ischemic stroke. MATERIALS AND METHODS: Phantoms with diffusion values
      approximating those expected in acutely infarcted and normal tissue were
      constructed from a mixture of agar and formaldehyde and imaged at varying b
      values (0-3000 mm(-2) second). Ten patients were imaged with multiple b values
      (500-2500 mm(-2) second) within 12 hours of stroke onset. RESULTS: Theoretical
      calculations showed that for any combination of diffusion coefficients there
      existed an optimal b value that was higher than the standard setting of 1000 mm(
      2) second, and this was confirmed by the phantom studies. In the patients,
      increasing b from 1000 to 1500 mm(-2) second increased Delta S (average, 22.4%; P
      = 0.001), but no consistent benefit was seen at b = 2000 mm(-2) second (P =
      0.408). This compared favorably with the average optimal b value of 1662 mm(- 2)
      second calculated from the patients. CONCLUSION: These results suggest that
      increasing the b value from 1000 to 1500 mm(-2) second would increase contrast
      between infarcted and normal tissue in the setting of acute ischemic stroke.

PMID- 11997902
TI  - Three-dimensional true-FISP imaging of the coronary arteries: improved contrast
      with T2-preparation.
AB  - PURPOSE: To evaluate the effectiveness of a T2-magnetization preparation scheme
      for improving coronary artery imaging with true fast imaging with steady-state
      precession (True-FISP). MATERIALS AND METHODS: Simulations were performed to
      compare the blood-myocardium signal difference with no T2-preparation to that
      with various T2-preparation times (24, 40, and 60 msec) using an
      electrocardiogram (ECG)-triggered, segmented True-FISP acquisition. Seven
      volunteers were imaged to evaluate the effectiveness of T2-preparation for
      coronary artery delineation using True- FISP and to optimize the T2-preparation
      time. RESULTS: Simulations showed that T2-preparation improved the signal
      difference between blood and myocardium over that without T2-preparation. The
      optimal T2- preparation time was determined to be 40 msec. In volunteer studies,
      a T2- preparation time of 40 msec provided a significant improvement in contrast-
      to-noise ratio (CNR) between the coronary arteries and myocardium over that
      without T2-preparation. It also showed a significant improvement in visualizing
      the distal portions of the coronary arteries. CONCLUSION: T2-preparation improves
      coronary artery delineation with True-FISP.

PMID- 11997903
TI  - Streamlined flow in the portal vein: demonstration with MR angiography.
AB  - PURPOSE: To demonstrate whether streamlining of the portal vein flow exists by
      evaluating the relative distribution of blood flowing from the superior
      mesenteric vein (SMV) and splenic vein (SV) into the portal venous system.
      MATERIALS AND METHODS: Fifteen healthy adult volunteers underwent MR angiography
      of the main portal vein (PV) and portal vein branches after an overnight fast.
      Transverse two dimension time-of-flight gradient echo sequences were obtained
      three times, in suspended expiration and inspiration, respectively, as follows:
      1) No presaturation slab, 2) presaturation slab across the SMV, 3) presaturation
      slab across the SV. Signal intensity (SI) measurements were obtained for all
      acquisitions. using regions of interest traced manually within the PV and portal
      branches. RESULTS: After presaturation of the SMV and SV during expiration, the
      overall SI average in the PV decreased by 47% +/- 8 (mean +/- SD) and 17% +/- 9,
      respectively. Right to left portal branch SI ratio and right-anterior to left
      posterior SI ratio in the PV were 0.91 +/- 0.09 and 1.02 +/- 0.08 at baseline,
      respectively. They decreased significantly (P < 0.05) to 0.87 +/- 0.09 and to
      0.95 +/- 0.09 after saturation of the SMV, and increased significantly to 0.95 +/
      0.08 and to 1.07 +/- 0.10 after saturation of the SV. CONCLUSION: MR angiography
      with selective saturation of the SMV and SV provided reproducible assessment of
      the respective contributions of the SMV and SV to portal flow, and allows
      demonstration that streamlining of splanchnic blood occurs in the portal vein of
      normal subjects.

PMID- 11997904
TI  - Correction of slab boundary artifact using histogram matching.
AB  - PURPOSE: To improve the imaging efficiency of multi-slab three-dimensional
      acquisitions by decreasing slab overlap and the number of blanked slices.
      MATERIALS AND METHODS: Application of the histogram matching technique for
      correction of the slab boundary artifact (SBA) due to non-ideal radiofrequency
      pulse profiles has been proposed. The technique was validated by studying its
      effectiveness in reducing the SBA in phantom images, as well as in proton density
      and T2-weighted brain images. RESULTS: The correction algorithm considerably
      decreases the disruption of image volume continuity due to the SBA, and improves
      slice-to-slice intensity continuity. CONCLUSION: The proposed technique can
      greatly reduce the SBA when the SBA can be described as a global intensity
      variation along the slab. The technique may be used to improve imaging efficiency
      of the multi-slab three-dimensional fast spin-echo sequences by decreasing the
      amount of required slab overlap.

PMID- 11997905
TI  - Impact factors in scientific journals.

PMID- 11997943
TI  - Base-induced 1,4-elimination: insights from theory and mass spectrometry.
AB  - Experimental and theoretical studies on gas-phase base-induced 1,4-elimination
      reactions are summarized and discussed. The emphasis is on the synergy that is
      achieved by combining the complementary data from mass spectrometry and
      theoretical chemistry. The scope and applications of 1,4-eliminations are
      discussed and compared with other elementary reactions; e.g., 1,2-elimination and
      aliphatic (S(N)2) and allylic (S(N)2') nucleophilic substitution. Furthermore,
      the syn versus anti stereochemistry of 1,4-elimination reactions and the effect
      of E versus Z stereochemistry of the substrate are examined. Particular attention
      is paid to the mechanistic nature of 1,4-elimination, i.e., E2 or E1cb, as well
      as special features such as the single-well E2 and E1cb mechanism. Also, new
      results from density functional theory computations (BP86/TZ2P) are presented.

PMID- 11997944
TI  - Practical implications of some recent studies in electrospray ionization
      fundamentals.
AB  - In accomplishing successful electrospray ionization analyses, it is imperative to
      have an understanding of the effects of variables such as analyte structure,
      instrumental parameters, and solution composition. Here, we review some
      fundamental studies of the ESI process that are relevant to these issues. We
      discuss how analyte chargeability and surface activity are related to ESI
      response, and how accessible parameters such as nonpolar surface area and
      reversed phase HPLC retention time can be used to predict relative ESI response.
      Also presented is a description of how derivitizing agents can be used to
      maximize or enable ESI response by improving the chargeability or hydrophobicity
      of ESI analytes. Limiting factors in the ESI calibration curve are discussed. At
      high concentrations, these factors include droplet surface area and excess charge
      concentration, whereas at low concentrations ion transmission becomes an issue,
      and chemical interference can also be limiting. Stable and reproducible non
      pneumatic ESI operation depends on the ability to balance a number of parameters,
      including applied voltage and solution surface tension, flow rate, and
      conductivity. We discuss how changing these parameters can shift the mode of ESI
      operation from stable to unstable, and how current-voltage curves can be used to
      characterize the mode of ESI operation. Finally, the characteristics of the ideal
      ESI solvent, including surface tension and conductivity requirements, are
      discussed. Analysis in the positive ion mode can be accomplished with acidified
      methanol/water solutions, but negative ion mode analysis necessitates special
      constituents that suppress corona discharge and facilitate the production of
      stable negative ions.

PMID- 11997945
TI  - Radical approaches to probe protein structure, folding, and interactions by mass
      spectrometry.
AB  - This review describes mass spectrometry-based strategies and investigations to
      determine protein structure, folding dynamics, and protein-protein interactions
      in solution through the use of radical reagents. The radicals are generated in
      high flux within microseconds from synchrotron radiation and discharge sources,
      and react with proteins on time scales that are less than those often attributed
      to structural reorganization and folding. The oxygen-based radicals generated in
      aqueous solution react with proteins to effect limited oxidation at specific
      amino acids throughout the sequence of the protein. The extent of oxidation at
      these residue markers is highly influenced by the accessibility of the reaction
      site to the bulk solvent. The extent of oxidation allows protection levels to be
      measured based on the degree to which a reaction occurs. A map of a protein's
      three-dimensional structure is subsequently assembled as in a footprinting
      experiment. Protein solutions that contain various concentrations of substrates
      that either promote or disrupt dynamic structural transitions can be investigated
      to facilitate site-specific equilibrium and time-resolved studies of protein
      folding. The radical-based strategies can also be employed in the study of
      protein-protein interactions to provide a new avenue for investigating protein
      complexes and assemblies with high structural resolution. The urea-induced
      unfolding of apomyoglobin and the binding of gelsolin to actin are among the
      systems presented to illustrate the approach.

PMID- 11997946
TI  - Proteins in vacuo: denaturing and folding mechanisms studied with computer
      simulated molecular dynamics.
AB  - Mounting evidence from experiments suggests that the native fold in solution is
      metastable in dehydrated proteins. Results from a number of experiments that use
      mass spectrometry indicate also that folding-unfolding transitions take place in
      protein ions even in the absence of water. These observations on anhydrous
      proteins call for a re-evaluation of our understanding of the folding transition.
      In this context, computer-assisted simulations are an important complementary
      tool. Here, we provide an overview of recent progress on the simulation of
      proteins in vacuo. In particular, we discuss the response of proteins and protein
      ions to perturbations that trigger unfolding and re-folding transitions. By
      comparing the general patterns emerging from theory and experiment, we propose a
      series of new measurements that could help to validate, and improve, current
      simulation models.

PMID- 11997948
TI  - Statistical analysis for article: comparison of sampling methods for obtaining
      accurate coagulation values in hemodialysis patients with heparinized central
      venous catheters.

PMID- 11997949
TI  - Safety surveillance in drug development: understanding the process and its
      implications for nephrology nursing.
AB  - The more frequent introduction of new drugs and devices to the marketplace,
      including an increase in the number of trials, requires nephrology nurses to
      better understand the process and the implications for their practice. This
      article explains the pre- and post-marketing phases of drug development and
      describes the post-marketing safety surveillance of all FDA-approved drugs.

PMID- 11997950
TI  - Hyperhomocysteinemia in end stage renal disease: is treatment necessary?
AB  - Hyperhomocysteinemia occurs in 85% of patients with end stage renal disease
      (ESRD) and may contribute to their increased risk of cardiovascular disease
      (CVD). This population experiences excess morbidity and mortality due to CVD,
      presenting a unique challenge in terms of preventative medicine. The treatment of
      hyperhomocysteinemia in the renal population has been a topic recently considered
      in published studies. It is thought, but not yet supported by evidence, that
      lowering homocysteine (Hcy) levels in ESRD patients will decrease the incidence
      of CVD. Nephrology nurses need to be aware of the pathophysiology, treatment, and
      current research regarding hyperhomocysteinemia in patients with ESRD and
      integrate this knowledge into clinical practice.

PMID- 11997951
TI  - Nursing experience with daily dialysis at El Camino Hospital.
AB  - This article describes the daily dialysis experience of patients at El Camino
      Dialysis Services (ECDS) and discusses the nursing issues affected by daily
      dialysis. As the renal population grows, the treatment of end stage renal disease
      (ESRD) needs further examination to improve quality of life, reduce mortality
      rates, and lower costs. There are several reports of improved well-being in
      patients receiving increased frequency of dialysis. Patients at ECDS on daily
      dialysis demonstrate clinical improvement with a stable dialysis and fewer
      intradialytic symptoms. New technology for home and clinic is needed to improve
      efficiency and quality of care.

PMID- 11997952
TI  - Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: pathophysiology
      and management.
AB  - Pathogenic mechanisms of renal injury by thrombotic microangiopathies present a
      challenge to the multidisciplinary team caring for a patient with thrombotic
      thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). First recognized 77
      years ago as a rare disorder characterized by reversible platelet aggregation in
      the microcirculation causing ischemia in various organs, the prognosis was always
      fatal. In the past 20 years, due to effective treatment with plasma exchange
      therapy, there has been a decline in the mortality rate to 10-20%. The classic
      pentad of symptoms of TPP-HUS include thrombocytopenia, microangiopathic
      hemolytic anemia, neurologic abnormalities, fever, and renal impairment.
      Frequency of TTP-HUS appears to be increasing. Due to the urgent need for a
      diagnosis, sufficient diagnostic criteria for TTP-HUS are currently
      thrombocytopenia and microangiopathic hemolytic anemia in the absence of another
      apparent cause. It is imperative to have a solid understanding of the
      pathophysiology and current standards of practice of TTP-HUS in order to
      facilitate positive patient outcomes in this unique group of patients.

PMID- 11997953
TI  - Weekly administration of high-dose sodium ferric gluconate is safe and effective
      in peritoneal dialysis patients.
AB  - This report describes the safety and efficacy of high-dose sodium ferric
      gluconate in 18 peritoneal dialysis (PD) patients. Nine patients received low
      dose (125 mg) and 9 patients received high-dose (250 mg) sodium ferric gluconate
      once per week for 8 or 4 weeks, respectively, followed by a maintenance dose once
      every 4 weeks. Patients in both groups had low iron saturation before treatment
      (hemoglobin [Hgb] < 11 g/dl, transferrin saturation [TSAT] approximately 20%, and
      serum ferritin < 250 ng/ml). After treatment, TSAT and ferritin significantly
      increased in both the low-dose (ferritin 465 +/- 292 ng/ml and TSAT 33.5 +/-
      6.9%) and high-dose (ferritin 622 +/- 339 ng/ml and TSAT 35.0 +/- 25.7%) groups
      compared to baseline. Hemoglobin levels also increased in both groups, but this
      was not statistically significant. No adverse reactions or transferrin
      oversaturation with high-dose sodium ferric gluconate were observed. In
      conclusion, high-dose sodium ferric gluconate was safe, convenient, and effective
      in treating iron deficiency in PD patients.

PMID- 11997954
TI  - Hemoglobin levels, cardiovascular disease, and left ventricular hypertrophy in
      patients with chronic kidney disease. Case study of the anemic patient.
AB  - Cardiovascular disease is the primary cause of morbidity and mortality in
      patients with chronic kidney disease. Anemia, a well-defined risk factor for
      cardiovascular disease, has been shown to contribute to the development of angina
      pectoris, ischemic events, and left ventricular hypertrophy. Data indicate that
      these cardiovascular-related disorders are often ameliorated or reversed in
      patients who maintain hemoglobin (Hb) levels in the 11 to 12 g/dL range
      recommended by NKF-K/DOQI. Conversely, Hb levels below 11 g/dL result in an
      increase in cardiovascular disorders and a 2.9-fold increased risk of death.
      Nephrology nurses should understand the interplay between Hb levels and
      cardiovascular disease, and how their efforts to maintain Hb levels > or = 11
      g/dL can positively affect patient outcomes.

PMID- 11997955
TI  - Fistula cannulation: the buttonhole technique.

PMID- 11997956
TI  - Initiatives in quality care at the end of life.

PMID- 11997957
TI  - Providing support to quit smoking.

PMID- 11997958
TI  - Haemophilia.
AB  - This Factfile examines haemophilia, a condition now usually treated by specially
      trained staff in modern, comprehensive care centres.

PMID- 11997959
TI  - Involving patients in discussions of do-not-resuscitate orders.
AB  - Despite continued investment in training and equipment, the chance of a good
      outcome following the invasive technique of cardiopulmonary resuscitation in
      hospital remains low. Given these facts, early and full discussion of do-not
      resuscitate orders with certain patients and their relatives and the use of
      advance directives will help to clarify this issue.

PMID- 11997960
TI  - The classification, grading and staging of cancer development.
AB  - Many patients see cancer as one disease whereas it is a collection of diseases
      with several common features. This month's study paper looks at the biology of
      cancer and explores the classification and staging of its complex disease
      processes. Such information is useful for all nurses, who frequently care for
      patients undergoing tests for cancer or receiving treatment.

PMID- 11997961
TI  - Exudate theory and the clinical management of exuding wounds.
AB  - When contained within the wound space, exudate performs a valuable role in wound
      healing. However, managing wounds with high levels of exudate is a commonly cited
      clinical problem. High levels of exudate cause problems in terms of selecting
      appropriate dressings and also in preventing potential damage to the surrounding
      skin caused by contact with exudate.

PMID- 11997962
TI  - The impact of national minimum standards on care homes.
AB  - Nursing and residential homes have escaped the numerous reorganisations and
      initiatives introduced to the NHS in recent years. However, this month new
      legislation is introduced that will dramatically change the way care is delivered
      and inspected. This paper describes how the new Care Standards Act will affect
      the lives of staff and residents in care homes.

PMID- 11997963
TI  - Diuretics.

PMID- 11997964
TI  - Ward leadership: balancing the clinical and managerial roles.
AB  - This qualitative study investigated ward managers' experiences of combining a
      clinical leadership role with the managerial and administrative parts of their
      job. Ward managers saw their main task as one of developing their staff and
      improving the quality of their service, yet found balancing their different roles
      problematic.

PMID- 11997965
TI  - Supporting clinical leaders in achieving organisational change.
AB  - Clinical leaders in nursing may feel stuck in the middle of conflicting demands
      from the various members of their organisation and patients' needs. The LEO
      programme aims to help these clinical leaders identify their problems, agree
      action plans and ask for the support they need in bringing about positive change
      in their workplace.

PMID- 11997966
TI  - Promoting effective rehabilitation via nurse-initiated patient transfer.
AB  - The transfer of patients from a district general hospital to community hospitals
      for rehabilitation is a key part of their care. Thorough assessment and
      preparation of the patient and his or her relatives is essential. Senior nurses
      in one trust set up a project to improve this transfer process for patients by
      introducing a nurse-to-nurse referral project.

PMID- 11997967
TI  - The needs of patients requiring home enteral tube feeding.
AB  - A report by the British Artificial Nutrition Survey of the British Association
      for Parenteral and Enteral Nutrition has highlighted the needs of patients using
      home enteral tube feeding. Many are frail and elderly and require careful
      discharge planning from hospital and co-ordinated, multidisciplinary care in
      nursing homes or their own homes on return to the community.

PMID- 11997968
TI  - The cost-effectiveness of outreach respiratory care for COPD patients.
AB  - An acute respiratory assessment service was established in a hospital that serves
      an area with a large number of COPD patients. The service aims to prevent
      unnecessary hospital admissions and provides a detailed patient assessment,
      treatment at home where appropriate and support. An economic evaluation
      demonstrated that the service was also cost effective.

PMID- 11997969
TI  - Pesticide soil sorption parameters: theory, measurement, uses, limitations and
      reliability.
AB  - The soil sorption coefficient Kd and the soil organic carbon sorption coefficient
      KOC of pesticides are basic parameters used by environmental scientists and
      regulatory agencies worldwide in describing the environmental fate and behavior
      of pesticides. They are a measure of the strength of sorption of pesticides to
      soils and other geosorbent surfaces at the water/solid interface, and are thus
      directly related to both environmental mobility and persistence. KOC is regarded
      as a 'universal' parameter related to the hydrophobicity of the pesticide
      molecule, which applies to a given pesticide in all soils. This assumption is
      known to be inexact, but it is used in this way in modeling and estimating risk
      for pesticide leaching and runoff. In this report we examine the theory, uses,
      measurement or estimation, limitations and reliability of these parameters and
      provide some 'rules of thumb' for the use of these parameters in describing the
      behavior and fate of pesticides in the environment, especially in analysis by
      modeling.

PMID- 11997970
TI  - The relative toxicities of insecticides to earthworms of the Pheretima group
      (Oligochaeta).
AB  - An artificial soil test was used to determine the LC50 values of carbaryl,
      chlorpyrifos, imidacloprid, cyfluthrin and fipronil against earthworms of the
      Pheretima group. For a 24-h interval, carbaryl was the most toxic to earthworms
      (LC50 = 77 mg kg-1), followed by imidacloprid (155 mg kg-1), cyfluthrin (351 mg
      kg-1), chlorpyrifos (390 mg kg-1) and fipronil (> 8550 mg kg-1) as the least
      toxic. For the 48-h and 7-day intervals, imidacloprid was the most toxic to
      earthworms (LC50 = 5 mg kg-1 and 3 mg kg-1 respectively), followed by carbaryl
      (16 mg kg-1; 9 mg kg-1), cyfluthrin (128 mg kg-1; 110 mg kg-1), chlorpyrifos (330
      mg kg-1; 180 mg kg-1) and the least toxic was fipronil (> 8550 mg kg-1 both
      intervals). The surface application rates required to achieve these values are
      compared with the rates recommended for the control of turfgrass pests.

PMID- 11997971
TI  - Identification of alternatives for the management of foliar nematodes in
      floriculture.
AB  - The foliar nematodes, Aphelenchoides spp, have emerged as important pests of
      ornamentals in North America during the last decade. Due to the ban on the use of
      potentially toxic pesticides, there are currently no nematicides registered to
      manage foliar nematodes on ornamentals. Therefore, we have evaluated a biological
      [Burkholderia cepacia (syn Pseudomonas cepacia)], two plant products [clove
      (Syzygium aromaticum) extract and Nimbecidine (azadirachtin)] and twelve chemical
      pesticides registered for the management of insects, mites, slugs or diseases of
      ornamentals, against Aphelenchoides fragariae on the most popular ornamental,
      hosta (Hosta spp), for two consecutive years. We found ZeroTol (270 g liter-1
      peroxyacetic acid), currently labeled as a broad-spectrum fungicide/algicide, to
      be a very potent nematicide that killed 100% of the nematodes in water
      suspension. It also caused over 70% reduction in A fragariae population in soil
      and in the leaves without any phytotoxicity. B cepacia caused 67-85% reduction in
      A fragariae population in leaves and 50% reduction in the soil whereas
      insecticidal soap caused over 72% reduction in leaves and 61% reduction in the
      soil. Clove extract and Nimbecidine did not show any potential for the control of
      A fragariae on hosta. Although all twelve chemical pesticides were effective in
      reducing the population of A fragariae in the soil 45 days after treatment (DAT),
      only diazinon 475 g liter-1 EC, trichlorfon 800 g kg-1 SP, ethoprophos 100 g kg-1
      GR, oxamyl 100 g kg-1 GR and ZeroTol caused over 70% reduction in nematode
      population compared with the control. In the leaves, only diazinon EC,
      trichlorfon SP, insecticidal soap, oxamyl GR and ZeroTol consistently caused over
      70% nematode population reduction compared with the control at 45 DAT in both
      years. Thus, only diazinon EC, trichlorfon SP, oxamyl GR and ZeroTol consistently
      caused over 70% reduction in nematode population both in soil and leaves. Due to
      the recent ban by the US Environmental Protection Agency on the use of the first
      three of these formulations, only ZeroTol would serve as an effective tool to
      manage foliar nematodes in ornamentals. Although not as effective as ZeroTol in
      the soil, insecticidal soap is the only other alternative for foliar nematode
      management.

PMID- 11997972
TI  - Evaluation of food additives and low-toxicity compounds as alternative chemicals
      for the control of Penicillium digitatum and Penicillium italicum on citrus
      fruit.
AB  - The effectiveness of low-toxicity chemicals as possible alternatives to synthetic
      fungicides for the control of post-harvest green and blue moulds of citrus was
      evaluated. A preliminary selection of chemicals, mostly common food additives,
      was made through in vivo primary screenings with oranges artificially inoculated
      with Penicillium digitatum or P italicum. Selected compounds and mixtures were
      tested as heated solutions in small-scale trials. Immersion of artificially
      inoculated oranges or lemons for 120 s in solutions at 40.6 degrees C and natural
      pH of potassium sorbate (0.2 M), sodium benzoate (0.2 M) or mixtures (0.1 + 0.1
      M) of potassium sorbate with sodium benzoate, sodium propionate or sodium acetate
      were the most effective organic acid salts tested and reduced green mould by 70
      80% after 7 days of storage at 20 degrees C. The mixtures did not significantly
      enhance the effectiveness of potassium sorbate or sodium benzoate alone. These
      solutions were as effective as sodium carbonate or calcium polysulphide
      treatments and, in general, they were more effective on lemons than on oranges.
      Satisfactory control of green and blue moulds was obtained by dipping oranges for
      150 s in solutions of sodium molybdate (24.2 mM) or ammonium molybdate (1.0 mM)
      at 48 or 53 degrees C, but not at 20 degrees C. At 53 degrees C, however, the
      effectiveness of hot water was not enhanced by either molybdate. Molybdenum salts
      at higher concentrations were phytotoxic and stained the fruit. At non-phytotoxic
      concentrations, the effectiveness of these solutions was more influenced by
      temperature than by concentration. In general, the inhibitory effects of all
      compounds tested were not fungicidal but fungistatic and not very persistent. In
      conclusion, potassium sorbate, sodium benzoate and ammonium molybdate, among the
      wide range of chemicals tested, were superior for the control of post-harvest
      Penicillium decay of citrus fruit.

PMID- 11997973
TI  - Measurement of xylem translocation of weak electrolytes with the pressure chamber
      technique.
AB  - Xylem translocation and root uptake of weak electrolytes were investigated with
      the pressure chamber technique (PCT) using de-topped soybean plants. Two
      compounds were organic bases (fenpropimorph and imazalil) and four were organic
      acids (bentazone, primisulfuron-methyl, rimsulfuron and triasulfuron). The
      compounds covered a wide range of log KOW and pKa values. Concentrations in
      external solution and in xylem sap were measured by HPLC at pH values in external
      solution of 4.5, 6.5 and 8.5. For weak bases, translocation was higher at low pH
      and the transpiration stream concentration factors (TSCF) were in the range 0.31
      0.95. At pH 8.5, the concentrations in leaking xylem sap were very low for
      fenpropimorph, and steady-state was probably not reached. For weak acids, TSCF
      values derived with external pH from 4.5 to 8.5 were in the range 0.55-1.50 for
      primisulfuron-methyl, 0.64-1.35 for rimsulfuron, 0.81-0.93 for triasulfuron and
      0.69-0.92 for bentazone. The variation of TSCF of the weak electrolytes was much
      smaller in these PCT experiments than in recent experiments with intact plants.
      The likely reason is that de-topped soybean plants in the pressure chamber seemed
      to be unable to regulate their xylem sap pH, which was almost identical to the pH
      in external solution. Without pH differences, the ion-trap process, which is
      responsible for accumulation or exclusion of weak acids and bases in the xylem of
      living plants, does not take place. Model simulations carried out for intact and
      de-topped plants supported this hypothesis. By variation of the pH of the xylem
      sap, good agreement between measurements and simulations could be achieved.

PMID- 11997974
TI  - PCR-based detection of resistance to acetyl-CoA carboxylase-inhibiting herbicides
      in black-grass (Alopecurus myosuroides Huds) and ryegrass (Lolium rigidum gaud).
AB  - A simple method based upon allele-specific PCR was developed to detect an
      isoleucine-leucine substitution in the gene encoding chloroplastic acetyl
      coenzyme A carboxylase (ACCase) in two gramineous weeds: Lolium rigidum Gaud and
      Alopecurus myosuroides Huds. Analysis of 1800 A myosuroides and 750 L rigidum
      seedlings showed that the presence of ACCase leucine allele(s) conferred cross
      resistance to the cyclohexanedione herbicide cycloxydim and to the
      aryloxyphenoxypropionate herbicides fenoxaprop-P-ethyl and diclofop-methyl.
      Seedlings containing ACCase leucine allele(s) could be either sensitive or
      resistant to the aryloxyphenoxypropionate herbicides haloxyfop-P-methyl and
      clodinafop-propargyl. Successful detection of resistant plants in a field
      population of A myosuroides was achieved using this PCR assay. Using it with
      basic molecular biology laboratory equipment, the presence of resistant leucine
      ACCase allele(s) can be detected within one working day.

PMID- 11997975
TI  - Molluscicidal and anti-feedant activities of diterpenes from Euphorbia paralias
      L.
AB  - Nine known diterpene polyesters of segetanes, jatrophenes and paralianes have
      been isolated from the aerial parts of Euphorbia paralias L. The molluscicidal
      activity of isolated compounds was evaluated on Biomphalaria alexandrina
      (Ehrenberg). Paraliane diterpene, (2S,3S,4R,5R,6R,8R,12S,13S,14R,15R)-5,8,14
      triacetoxy-3-benzoyloxy-15- hydroxy-9-oxo-paraliane, was the most potent compound
      against the snail. Anti-feedant activity was tested by a conventional leaf disc
      method against third-instar larvae of Spodoptera littoralis (Boisd). Jatrophene
      diterpene, (2R,3R,4S,5R,7S,8R,13R,15R)-2,3,5,7,15-pentaacetoxy-8-angeloyloxy
      14,15- dioxojatropha-6(17)-11E-diene, had the highest anti-feedant activity among
      the compounds tested.

PMID- 11997976
TI  - Nicotinic acetylcholine receptor binding of imidacloprid-related diaza compounds
      with various ring sizes and their insecticidal activity against Musca domestica.
AB  - Fifteen 5-substituted 1-(6-chloro-3-pyridylmethyl)-2-nitromethylene-1,3-
      diazacyclohexanes and three other related compounds having a five- or seven
      membered ring were synthesized and their biological activities were measured in
      vivo and in vitro. The insecticidal (in vivo) activity was evaluated against
      houseflies Musca domestica L under synergistic conditions with propargyl propyl
      phenyl phosphonate and piperonyl butoxide. The binding activity of each compound
      to nicotinic acetylcholine receptor in vitro was measured using [125I] alpha
      bungarotoxin. The insecticidal activities of the unsubstituted diazacyclohexane
      analogues were slightly higher than those of the imidazolidine analogues, but the
      enlargement of ring size to diazacycloheptane lowered the activity. Substitution
      of 1,3-diazacyclohexane or imidazolidine rings was not generally favourable for
      the activity, but the unsubstituted 1,3-diazacyclohexane analogue showed the
      highest binding activity. Ring substitutions and ring enlargement decreased the
      activity 100-30,000-fold.

PMID- 11997977
TI  - Insecticidal properties of essential plant oils against the mosquito Culex
      pipiens molestus (Diptera: Culicidae).
AB  - The insecticidal activities of essential oil extracts from leaves and flowers of
      aromatic plants against fourth-instar larvae of the mosquito Culex pipiens
      molestus Forskal were determined. Extracts of Myrtus communis L were found to be
      the most toxic, followed by those of Origanum syriacum L, Mentha microcorphylla
      Koch, Pistacia lentiscus L and Lavandula stoechas L with LC50 values of 16, 36,
      39, 70 and 89 mg litre-1, respectively. Over 20 major components were identified
      in extracts from each plant species. Eight pure components (1,8-cineole,
      menthone, linalool, terpineol, carvacrol, thymol, (1S)-(-)-alpha-pinene and (1R)
      (+)-alpha-pinene) were tested against the larvae. Thymol, carvacrol, (1R)-(+)
      alpha-pinene and (1S)-(-)-alpha-pinene were the most toxic (LC50 = 36-49 mg litre
      1), while menthone, 1,8-cineole, linalool and terpineol (LC50 = 156-194 mg litre
      1) were less toxic.

PMID- 11997978
TI  - Photodegradation of diafenthiuron in water.
AB  - Diafenthiuron, 1-tert-butyl-3-(2,6-di-isopropyl-4-phenoxyphenyl)thiourea, is an
      effective insecticide and acaricide. Sunlight degradation of diafenthiuron in
      various aqueous solutions and pure hexane yielded two major identified products:
      1-tert-butyl-3-(2,6-di-isopropyl-4-phenoxyphenyl)-carbodiimide (CGA-140,408) and
      1-tert-butyl-3-(2,6-di-isopropyl-4-phenoxy-phenyl)urea (CGA-177,960). CGA-140,408
      was further photo-transformed into CGA-177,960 by sunlight. Direct photolysis
      appeared to be a major photolysis pathway of diafenthiuron in the environment.
      Photodegradation of CGA-140,408 and CGA-177,960 was enhanced in humic acid water,
      paddy water and aqueous acetone solutions, and followed first-order kinetics.
      Isopropanol (a radical quencher) and de-aeration strongly inhibited the
      photolysis of these chemicals, which suggested oxygen radical-mediated reactions.

PMID- 11997979
TI  - Biological activity of astilbin from Dimorphandra mollis against Anticarsia
      gemmatalis and Spodoptera frugiperda.
AB  - Astilbin was isolated in high yield from Dimorphandra mollis, and its
      insecticidal and growth inhibiting activity by stomach ingestion were evaluated
      against Anticarsia gemmatalis and Spodoptera frugiperda. The insecticidal
      activity of astilbin, the weight reduction of the larval phase and the
      prolongation of the larval and pupal phases were verified for both species.
      Astilbin was identified on the base of its NMR, MS and physical data.

PMID- 11997980
TI  - Photosynthetic apparatus of purple bacteria.

PMID- 11997981
TI  - Development, learning and memory in large random networks of cortical neurons:
      lessons beyond anatomy.

PMID- 11997982
TI  - Triplex-forming oligonucleotides: principles and applications.

PMID- 11997983
TI  - Gene therapy. Hidden X factor.

PMID- 11997984
TI  - Primary care. It's no contest.

PMID- 11997985
TI  - It takes two, baby.

PMID- 11997986
TI  - Is the NHS safe in the government's hands?

PMID- 11997989
TI  - Am I wasting my time completing my learning disability nursing training?

PMID- 11997990
TI  - 'Don't take us for granted'.

PMID- 11997991
TI  - A portrait of the nurse as a young man.

PMID- 11997992
TI  - God is other people.

PMID- 11997993
TI  - Nursing the nurses: why staff need support.
AB  - A research project exploring job satisfaction levels among nursing and therapy
      staff working with stroke patients has unearthed wider issues regarding the
      support of nurses. Most participants were happy in their jobs and with their
      training opportunities. Nurses, in particular, felt very proud of their vocation.
      But they also reported more stress and had higher absenteeism rates than their
      colleagues. The authors analyse and discuss their findings and argue that nurses
      should not be subjected to fundamental occupational stresses without improved
      support systems.

PMID- 11997994
TI  - The fear-avoidance model: helping patients to cope with disfigurement.
AB  - Last week's article established that body disfigurement affects a considerable
      number of people and causes them significant distress. It also explored how a
      cognitive behavioural model of psychological disturbance might inform our
      understanding of the difficulties faced by people with disfigurement. This week's
      article examines the practical application of the fear-avoidance model and
      discusses how it can be used by nurses as a means of providing general advice and
      more specialist intervention.

PMID- 11997996
TI  - Nursing with dignity. Part 8: Islam.
AB  - This article describes the main teachings and customs of Islam. It offers some
      guidelines to enable nurses to provide sensitive and appropriate care to Muslim
      patients.

PMID- 11997997
TI  - The training needs of primary care nurses in relation to mental health.
AB  - Nurses working in primary care are in the front line of providing mental health
      services. The National Service Framework for Mental Health sets out new standards
      in service provision, yet this key group of staff is, in many cases, not fully
      equipped with the necessary skills and knowledge to comply. Michael Nash has
      conducted a training needs analysis of primary care nurses in a London borough.
      The results highlight areas of concern and indicate a way forward to ensure
      appropriate mental health care training for these professionals.

PMID- 11997998
TI  - Professional development. Medicines. 2. Administration of medicines.

PMID- 11998000
TI  - Sildenafil citrate.

PMID- 11998001
TI  - Beyond aspirin: how glycoprotein inhibitors ease acute coronary syndromes.
AB  - Glycoprotein IIb/IIIa receptor inhibitors can improve vessel patency for patients
      with myocardial infarction and angina. Patients who receive these drugs can be
      managed more conservatively, without invasive procedures, and may have less risk
      of recurrent infarction and death.

PMID- 11998002
TI  - Impedance cardiography: a noninvasive way to monitor hemodynamics.
AB  - Impedance cardiography is a noninvasive way to measure hemodynamics and thoracic
      fluid status that can be quickly implemented by the nurse in any setting. This
      article describes the principles and use of impedance cardiography and how it can
      allow nurses to improve patient outcomes through early recognition of hemodynamic
      abnormalities.

PMID- 11998003
TI  - Animal-assisted therapy: an in-depth look.
AB  - Animal-assisted therapy has gained widespread support and application over the
      past few decades. This article reviews the history of animal-assisted therapy;
      discusses its present goals and applications, including those pertinent to
      critical care; and notes questions requiring further research.

PMID- 11998004
TI  - Treating tachyarrhythmias with radiofrequency catheter ablation.
AB  - Fast, safe, and effective, radiofrequency catheter ablation is becoming more
      common as a treatment for tachyarrhythmias. This article describes the procedure,
      which patients are eligible for it, and nursing considerations before, during,
      and after the procedure.

PMID- 11998005
TI  - Making ambulance transports safer for nurses.
AB  - Emergency medical vehicle collisions account for multiple deaths and thousands of
      injuries each year. Nurse leaders can make ambulance rides safer by reviewing the
      ambulance company's lights and sirens policy, supporting use of safety devices,
      and empowering nurses to demand safe driving practices.

PMID- 11998006
TI  - Win-win mentoring.
AB  - This article describes strategies to build and enhance mentor/protege
      relationships, expand nurses' experience, and help new nurses develop.

PMID- 11998007
TI  - When families need respite.

PMID- 11998008
TI  - Going it alone: the experiences of spouses of critically ill patients.
AB  - Spouses of critically ill patients are faced with major changes in
      responsibilities while their spouse is in the intensive care unit. Using grounded
      theory methods, this qualitative study investigated the changes in
      responsibilities and the impact these additional responsibilities (such as
      financial decision making and child care) had on patients' spouses. Patients'
      spouses need help to meet their needs and alleviate some stress so they can "be
      there" for their critically ill partner.

PMID- 11998009
TI  - Research to improve health care for low-income children.

PMID- 11998010
TI  - Advanced practice nursing: opportunities and challenges.
AB  - Planning for the future may not be easy but it is always worthwhile. Resources
      that can help in making choices include professional organizations such as the
      Kentucky Coalition of Nurse Practitioners and Nurse Midwives, KNA, American
      Academy of Nurse Practitioners, American College of Nurse Practitioners, the
      Internet, and the college and university Schools of Nursing. Taking control of
      one's destiny is the best gift that can be given to one's self. Increasing
      options for career development is just one of the benefits of pursuing
      educational goals. The first step is commitment to goal. Selecting the right
      specialty, planning how financial obligations will be met and choosing the
      program that best meets identified needs are steps that will follow. Health care
      changes are occurring at such a rapid pace the individual nurse may feel caught
      in a whirlwind without control. Making the choice to seek change will present its
      own challenges but without change, growth is impossible. For those considering an
      Advanced Practice role, making the commitment, outlining a plan with each step
      clearly identified, reliance on a strong support system, and maintaining a vision
      of the completed goal will lead to success.

PMID- 11998011
TI  - "On a scale of 0 to 10".

PMID- 11998013
TI  - Integrative medicine--not only the future of healthcare, the future of nursing!

PMID- 11998014
TI  - Complementary and alternative medicine.

PMID- 11998015
TI  - "Excellence in Health Care Trust Fund" update.

PMID- 11998016
TI  - Methamphetamine affects individuals and communities.

PMID- 11998017
TI  - Living with fibromyalgia.

PMID- 11998018
TI  - Accountability for professional practice by licensed nurses.

PMID- 11998019
TI  - Advanced practice geriatric nursing education. New options in Kansas.
AB  - Knowledgeable practitioners with the skills needed to serve in a variety of
      clinical settings are the primary objective of the Adult-Geriatric Advanced
      Nursing Program and the FNP elective, Advanced Practice Nursing Care of the Frail
      Elderly. The continued blending of long term and acute care settings will further
      cloud and challenge the school responsible for educating APNs in the care of
      older adults, particularly the frail elderly. Education needs to provide
      flexibility for students through new service designs such as interactive computer
      courses. Nurses with an orientation to the future should consider geriatric
      nursing education.

PMID- 11998020
TI  - Things to know about health care "decision making" and advance directives.

PMID- 11998021
TI  - From barnyard to backyard: the potential for E-coli.

PMID- 11998022
TI  - Family Medical Leave Act.

PMID- 11998023
TI  - Improper use of bed rails.

PMID- 11998024
TI  - Preventing restraint deaths. JCAHO recommendations. Joint Committee on
      Accreditation of Healthcare Organizations.

PMID- 11998025
TI  - Occupational exposures in the healthcare workplace.

PMID- 11998026
TI  - Ethical decision making in assisted suicide.

PMID- 11998028
TI  - Cultural immersion: a teaching strategy.

PMID- 11998029
TI  - Transcultural nursing: a student's perspective.

PMID- 11998030
TI  - Implications of the Kansas Local Health Department Education and Salary Survey.

PMID- 11998031
TI  - Liability for the acts of others.

PMID- 11998032
TI  - Fighting to save nurses lives--ANA urges congress to pass new needlestick &
      sharps injury prevention act.

PMID- 11998033
TI  - Kansas Board of Nursing position statement on multistate regulation of nurses.
AB  - The Kansas State Board of Nursing cannot support multistate licensure under the
      current interstate compact language. Because each state determines the
      qualifications for the practice of nursing, the Kansas Attorney General believes
      the nurse licensure compact in its present form would be an unconstitutional
      delegation of legislative authority. Other practical issues of concern are the
      privacy and confidentiality of shared information, the ability to discipline
      licenses, the Board's ability to provide the information needed for the operation
      of the system, and lastly the cost to all licensees.

PMID- 11998034
TI  - Public health nursing at a cross road.

PMID- 11998035
TI  - Improving the public health of Kansas: an overview of recent developments and
      opportunities that exist.

PMID- 11998036
TI  - Neighborhood health project tries "old-new" direction.

PMID- 11998037
TI  - Everyone has a story.

PMID- 11998038
TI  - The identification and screening of men at high risk for developing prostate
      cancer.
AB  - It is estimated that the lifetime risk of being diagnosed with prostate cancer is
      1 in 5. The identification of risk factors, including age, African-American
      ancestry, family history, and possibly diet and environmental factors, has
      allowed health care professionals the opportunity to identify, screen, and study
      men at the greatest risk of developing prostate cancer. The risk factors, current
      screening tools, and the informed consent process for men participating in a
      prostate cancer screening program are outlined.

PMID- 11998039
TI  - Insights into the management of erectile dysfunction: Part II.
AB  - For the estimated 30 million men in the United States with erectile dysfunction
      (ED), treatment options are varied. What may be the best choice for one
      individual is not necessarily the right choice for someone else. It is essential
      that health care professionals have a thorough understanding of all available
      options so they can help their patients and partners make the best treatment
      choice for successful sexual satisfaction. A variety of available ED treatment
      options are outlined here.

PMID- 11998040
TI  - Comparison of catheter-securing devices.
AB  - Care of urethral urinary catheters is a major part of urologic nursing. Basic
      procedures, such as securing of urinary catheters, are poorly researched or
      reported in the literature. The question of how to secure a urinary catheter and
      with what device often relies on knowledge, availability of equipment, and on
      information supplied by manufacturers of commercial devices. Manufacturers claim
      that their devices are easier to apply, have longer "wear-times," add to patient
      comfort, prevent infection, and are thus more cost effective than the traditional
      adhesive tape and pin device. However, it was discovered in this study that
      sometimes the cheaper, more easily accessible option can still be the best for
      patients.

PMID- 11998041
TI  - Sowing seeds: transperineal implantation.
AB  - Prostate cancer, the second leading cause of male deaths in the United States,
      has increased by 126% since 1987 (Stephenson, 1998). Early diagnosis is
      attributed to public awareness and technologic advances. Multiple options for
      definitive treatment with equally positive outcomes dramatically influence the
      patient's decision-making process. One popular option for these patients is
      transperineal implantation of radioactive seeds into the prostate.

PMID- 11998042
TI  - Post-TURP incontinence.

PMID- 11998043
TI  - The 'me' disease.

PMID- 11998044
TI  - Getting ready for certification: male infertility.

PMID- 11998046
TI  - Reporting suspicions of elder abuse mandatory for nurses.

PMID- 11998047
TI  - Profile of Virginia Davidsaver, PhD, RN. A nurse looks at 50 years in the
      profession. Interview by Jen Cavalieri.

PMID- 11998049
TI  - Assessing pediatric pain.

PMID- 11998048
TI  - Continuing education for nurses: delegation.

PMID- 11998050
TI  - Handling a pediatric transport.
AB  - When minutes matter, being prepared can pave the way to a happier ending in
      heartrending situations. This article describes how to prepare for and handle
      transport of a critically ill or injured child.

PMID- 11998051
TI  - Noninvasive positive-pressure ventilation: averting intubation of the heart
      failure patient.
AB  - Mechanically ventilating patients with heart failure who have respiratory
      distress can increase hospital costs, complications, and mortality. A few studies
      have evaluated the use of noninvasive positive-pressure ventilation (NPPV) as an
      alternative treatment for these patients. This article describes NPPV and reviews
      its use in managing an acute exacerbation of heart failure.

PMID- 11998052
TI  - Responding to pediatric trauma.
AB  - Pediatric trauma care can seem daunting even to seasoned critical care nurses, if
      they have not worked frequently with young patients. Children differ from adults
      in significant anatomic and physiologic ways and require equipment, supplies, and
      medication dosages carefully tailored to their body size and weight. This article
      gives nurses a solid foundation in pediatric care by reviewing the differences
      between adult and child patients as well as the shared priorities involved in
      pediatric and adult trauma care.

PMID- 11998053
TI  - Nicardipine.

PMID- 11998054
TI  - Academia and practice: working together to provide continuing education.
AB  - Collaboration between academia and practice settings has been cited frequently in
      the literature on baccalaureate nursing curriculum. This article applies the
      concept of collaboration to the development of a continuing educational program
      for practicing cardiovascular nurses.

PMID- 11998055
TI  - How to lead departments outside your clinical competence.
AB  - Leading departments outside your clinical competence takes a special set of
      skills. Follow these approaches and enhance your transferable leadership skills
      to succeed.

PMID- 11998056
TI  - Measuring how acute care nurse practitioners affect outcomes.
AB  - Nurse-leaders need a way to measure acute care nurse practitioners' (ACNPs')
      performance and justify their positions. An objective documentation tool can help
      to evaluate ACNPs' work activities and measure performance and outcomes.

PMID- 11998057
TI  - Teaching patients about telemetry.
AB  - For patients on telemetry monitoring, knowledge is power--and comfort. This
      article describes how two nurses developed informational materials to help busy
      nurses give patients the information they need to set their minds at rest about
      telemetry.

PMID- 11998058
TI  - Factors related to recovery in coronary artery bypass graft surgery patients.
AB  - Many studies have examined the experiences of patients who have had coronary
      artery bypass graft (CABG) surgery. Research has suggested a relationship between
      patients' feelings of powerlessness and their recovery rate. This study examined
      recovery indicators and the degree of powerlessness CABG patients experienced,
      and identified ways nurses can encourage patients to participate in their
      recovery and feel back in control.

PMID- 11998059
TI  - Minor misgivings.

PMID- 11998060
TI  - Two steps forward, one step back.

PMID- 11998061
TI  - Sorrowful snapshots.

PMID- 11998062
TI  - Acute coronary syndrome: new advances and nursing strategies.
AB  - Glycoprotein IIb/IIIa receptor inhibitors are the newest therapy for acute
      coronary syndrome (ACS). This article reviews the pathophysiology of ACS, the
      role of glycoprotein IIb/IIIa receptor inhibitors, and nursing care for patients
      undergoing this therapy and coronary interventions.

PMID- 11998063
TI  - Using the ECG to identify pulmonary embolism.
AB  - Pulmonary embolism is frequently unrecognized in postoperative and medical
      patients. In this article, the author describes how to recognize this "great
      imitator" and protect patients from potentially fatal complications.

PMID- 11998064
TI  - Reducing risks while improving care.
AB  - The inherent risks in critical care and the vulnerability of its patients demand
      a rigorous attention to detail. This article gives the critical care nurse a
      sound basis in risk management principles and existing policies, including those
      of the Joint Commission on Accreditation of Healthcare Organizations.
      Understanding risk management can help nurses improve patient care while reducing
      the chances for litigation.

PMID- 11998065
TI  - Accept or divert ICU patients? A heated ethical debate.
AB  - Stretching scarce resources is more than a managerial issue. Should an
      understaffed ICU accept the patient or divert him to another facility? The
      intense "medical utility" controversy focuses on a situation that critical care
      nurses now face every day.

PMID- 11998066
TI  - Mastering neuromuscular blockade.
AB  - Learn how neuromuscular blocking agents work and how to assess and manage a
      patient receiving these drugs.

PMID- 11998067
TI  - Family perceptions of support interventions in the intensive care unit.
AB  - Family needs of critically ill patients have been well documented in nursing
      literature. However, few researchers have examined support interventions intended
      to meet these needs. This study examines which interventions provide the greatest
      benefit to critically ill patients' families and recommends nursing actions to
      meet families' support needs.

PMID- 11998068
TI  - Enhancing self-esteem among cardiac patients.
AB  - This study examined the development, implementation, and evaluation of a module
      to enhance self-esteem among patients in an outpatient cardiac clinic. Eighty
      percent of the subjects reported that activities such as exercise and social
      functions helped them feel better about themselves. This data supported the use
      of spirituality, interpersonal relationships, self-care activities, and self
      preservation concepts to enhance self-esteem in cardiac patients.

PMID- 11998069
TI  - The times, they are a-changing.

PMID- 11998070
TI  - Elder abuse topic of NNA Workshop.

PMID- 11998071
TI  - Mentors: a precious resource, handle carefully.

PMID- 11998072
TI  - Prepare for tomorrow, today!

PMID- 11998075
TI  - What exactly is chemical dependency treatment and what is expected of the client
      while involved in treatment?

PMID- 11998076
TI  - Working with people with developmental disabilities.

PMID- 11998077
TI  - Unionization: is it right for you?

PMID- 11998078
TI  - Will the prospective payment system leave nurses vulnerable?

PMID- 11998079
TI  - Tertiary care: a changing environment.

PMID- 11998080
TI  - Rehabilitation in the therapeutic riding arena.

PMID- 11998081
TI  - A near death experience through a daughter's eyes.

PMID- 11998082
TI  - Journal writing as a complementary therapy for reactive depression: a
      rehabilitation teaching program.
AB  - Brief, recurrent, reactive, or situational depression is a common and costly
      comorbidity that affects chronically ill patients and their family members. This
      article describes a program that teaches those individuals how to monitor and
      cope with symptoms of depression by writing daily in a journal. Twenty patients
      and family members attended teaching sessions at which videotaped scenes of other
      patients managing symptoms of depression were shown. After viewing the six
      scenes, participants wrote about their reactions to each scene and listed the
      emotions they had experienced that were similar to those shown in the tape. They
      were then asked to record daily for 4 months their emotions and reactions to
      situations and to also daily self-rate their levels of energy. They were also
      provided with a list of recommended activities in which to engage when they were
      depressed. Two psychiatric nurses evaluated the writings and concluded that the
      program was influential in helping patients and families overcome many
      emotionally draining reactions to adverse circumstances.

PMID- 11998083
TI  - An update in diabetes management.
AB  - Staying abreast of the numerous recent advances in diabetes management presents a
      challenge to healthcare professionals. This paper provides an overview of these
      changes and discusses their implications for rehabilitation caregivers and
      clients. Because of increased scientific knowledge of the disease, there have
      been changes in nomenclature, diagnostic criteria, and nutritional guidelines.
      Medications to improve control of diabetes and innovations in equipment have been
      developed. The concepts of intensive management and self-management have gained
      importance, as have reimbursement issues. An overview of these advances and their
      implications for nursing practice, may help nurses throughout the continuum of
      care to assist individuals with diabetes to enjoy the maximum quality of life
      possible.

PMID- 11998084
TI  - Multimodal chronic pain rehabilitation program: its effect on immune function,
      depression, and health behaviors.
AB  - This pilot study examined the effects of a multimodal pain rehabilitation program
      on the immune function, self-reported pain, depression levels, and health
      behaviors of patients with chronic back pain. It also estimated the relationships
      between self-reported pain levels, immune function, depression, and health
      behaviors. Data were collected at week 1 (baseline) and at week 4 (last week of
      treatment program) on a convenience sample of 23 patients. In general, the
      patients' mean T lymphocyte proliferation levels showed a decline from baseline
      to week 4, while natural killer cell activity showed a slight increase in cell
      lysis. None of the findings were statistically significant. Failure to detect
      significant differences may be attributed to a small effect size due to the
      relatively small sample size. The depression levels dropped significantly during
      the treatment program (p = .001). Reported levels of pain and health behaviors
      did not significantly change. More research is needed to determine treatment
      effects on immune function as well as relationships between pain levels, immune
      function, depression, and health behaviors in this patient population.

PMID- 11998085
TI  - Perceived losses following stroke.

PMID- 11998086
TI  - Dynamic infusion cavernosometry and cavernosography.
AB  - With erectile dysfunction's impact on society, the need for developing a
      comprehensive plan for accurate diagnosis is indicated. Dynamic infusion
      cavernosometry and cavernosography (DICC) offers an effective tool for evaluating
      the hemodynamic status of erectile dysfunction.

PMID- 11998087
TI  - The LoFric catheter: new technology improves an old technique.
AB  - The LoFric catheter is a hydrophilic, nonlatex plastic catheter for use in adults
      and children. Immersing the catheter in water produces a slippery, protective
      coating on the catheter. This protective coating prevents trauma to the mucosal
      surface. Because of its slippery surface even patients who have difficulty using
      a conventional catheter are usually able to use a LoFric catheter.

PMID- 11998088
TI  - Behind the scenes: partners' perceptions of quality of life post radical
      prostatectomy.
AB  - The purpose of this study was to determine the effects of the experience of a
      radical prostatectomy on the partners of men with prostate cancer. The women
      described the effects of the experience on their lives and on their partner's
      life. Descriptions included how they were informed of their partner's diagnosis,
      emotions at the time of the initial diagnosis, and the sources of information and
      the decision process that they and their partners used that lead to surgery. The
      effect of the experience on their quality of life including interpersonal and
      sexual relationships with their partner and the information that was needed to
      facilitate self-care after surgery were described. The women provided clear
      directions for improving the health care system in managing the cancer experience
      using a family-centered approach.

PMID- 11998089
TI  - The treatment of nonobstructive urinary retention with high-frequency
      transvaginal electrical stimulation.
AB  - The usefulness of timed voiding, cholinergic medications, and high-frequency
      electrical stimulation in women with symptomatic urinary retention was evaluated.
      Results indicated that symptomatic urinary retention can be treated with
      behavioral modification and high-frequency electrical stimulation. Optimal
      results were found in younger women with stable bladders.

PMID- 11998090
TI  - Getting ready for certification: benign prostatic hyperplasia.

PMID- 11998091
TI  - Treatments for overactive bladder.

PMID- 11998092
TI  - The art of leading with grace.
AB  - Uncivilized environments take their toll on people who work there. Cultures of
      distrust are created and there is no warmth, reverence, or love available for the
      healing work of health care. We can blame the staff, or we can look at ourselves
      and recognize that the staff is merely a reflection of ourselves. Gracious
      leaders create a gracious and loving staff who care for patients and their
      families in extraordinary ways.

PMID- 11998093
TI  - Needlestick injuries: prevention is key.

PMID- 11998094
TI  - Proposal #1. Preventing needle stick injury and prevention of blood borne
      diseases.

PMID- 11998095
TI  - Proposal #2. Shortage of registered nurses is detrimental to client care and
      safety.

PMID- 11998096
TI  - Proposal #3. Patients' bill of rights.

PMID- 11998097
TI  - Proposal #4. Prevention of school violence.

PMID- 11998098
TI  - Proposal #5. Nurse licensure compact.

PMID- 11998099
TI  - Assuring nursing competence.

PMID- 11998100
TI  - [Educational program for HIV/AIDS prevention].
AB  - The objective of this study is the evaluation of an educative program intended to
      bring scientific knowledge to common sense persons about HIV/AIDS prevention. A
      participative study was carried out with clients of a health center. To the
      development of the program, an educative game was used. It had 30 cards with
      verbal and non-verbal messages about the topic. The discussion about those
      messages were observed and recorded. The analysis of the data made possible the
      elaboration of themes categories: "men, women and preservative", "beliefs,
      attitudes, feelings and behavior", "pursuing meaning of life", "media and
      HIV/IDS". The evaluation of the program by the participants shows attainment to
      its objectives. The game was considered excellent to start the discussion about
      the topic and a good educational tool, in which knowledge raises freely from the
      encounter of scientific and common sense perspectives.

PMID- 11998101
TI  - [Nursing diagnosis and interventions in a patient with multiple organ failure --
      report of a case].
AB  - This study tries to identify Nursing Diagnoses and Interventions. It was done
      with a patient who was in critical health condition: multiple organs failure, in
      an Intensive Care Unit of a general hospital in Porto Alegre. The Case Study was
      the methodology used. Nursing Diagnoses is described mostly using NANDA Taxonomy.
      They are: Risk for Aspiration, Disuse Syndrome, Diarrhea, Risk for Infection,
      Impaired Tissue Integrity; and a Collaborative Problem was identified:
      Hypoglicemia. We have elaborated 34 Nursing Interventions for those diagnoses.

PMID- 11998102
TI  - [AIDS and the hospital institution: why to think/rethink about this
      relationship?].
AB  - Through the report of a situation occurred within the hospital institution, the
      article tries to focus on the way how the AIDS question has been thought in this
      enviroment. Furthermore, it broaches the possibility of compromising the hospital
      as a space for reflection and discussion. Through the analysis, it articulates
      the subjects implicated in the situation with gender, sex, sexuality, race and
      ethic questions. It also relates AIDS to risk groups, as a meaning to promote the
      occlusion, and to power relations within the hospital institution. As a
      conclusion, the article proposes more questions for us to think over our practice
      as professionals inserted in this context.

PMID- 11998103
TI  - [Care-research interface in nursing].
AB  - In this study, the authors have as a goal to discuss the care-investigation
      interface in the caring practice of Nursing in the hospital ambit, starting from
      their professional experiences. The bases of the discussion is the career/cared
      being. We surpass care as the object of research and the importance of
      investigation for the improvement of care quality. Interdisciplinarity is pointed
      out as one of the possible resources for the construction of integral care and of
      a therapeutical action that exceeds the biological, in a perspective of co
      participation, as well as the need of promoting and stimulating the
      accomplishment of investigations in the units of hospital care. The meaning of
      the investigation about care goes beyond its internality, requiring technical
      competence, ethical compromise and coherence among the different areas of
      knowledge which involves it. We enlighten the need of overcoming the dichotomies
      of caring/investigating, researching while caring, and caring while researching.
      We stress out the importance of creating research groups in Universities; the
      stimulus to the accomplishment of graduation courses with leave-out time from
      work; the availability of financial resources; and the incentive to subscribe
      periodicals and to acquire books.

PMID- 11998104
TI  - [Health, healthy family and healthy child: views and relationships of community
      agents].
AB  - This article reports the experience lived by the authors during their training
      time in one of the practical activities of the Nursing Teaching Course. In the
      context of a Continued Education Project developed with community agents of the
      Family Health Program, the research approaches a discussion that was triggered
      off on a meeting about the subject: "Health, Healthy Family and Healthy Child",
      when some manifestations of persons involved in the project were argued. The
      authors concluded that, as a pedogogic strategy, the use of group dynamics
      enlarges the possibilities of using the experience and knowledge that determines
      the person's action, as a teaching-learning process base.

PMID- 11998105
TI  - [Work overload in the perception of nurses working at hospitals].
AB  - This article presents the first part of a qualitative research in which we
      interviewed ten nurses that were burnout with work and ten that were not. The
      objective was to comprehend how they experience burnout situations. The
      interviews were analysed according to Content Analysis Technique. The "overload
      of work" category was the most frequent in the participants' speeches. All the
      nurses with burnout made reference to this category about tem times, while
      relating the situations they consider to cause burnout. In the other hand, nurses
      without burnout only related to it once or twice. The overload of work appears as
      a consequence of "accumulated functions" on their daily activities and from the
      consequent "time pressure" they suffer. The speeches reflect the nurse's work
      organization which, frequently, is difficult to practice in a strict way, leading
      some professionals to make decisions sometimes considered contradictory.

PMID- 11998106
TI  - [Field work in nursing qualitative research].
AB  - The objective of this study was to reflect upon the difficulties experienced by
      the authors while doing field work in qualitative researches during their Masters
      and Doctoral Nursing courses.

PMID- 11998107
TI  - [Absenteeism as a variable in human resource planning in nursing].
AB  - The study of absenteeism in Nursing is an important item that subsizes planning
      and adjusting human resources, regarding the continuity of nursing labor 24 hours
      a day in a hospital. Absenteeism is the absence from work at moments workers
      should be regularly executing their duties. We identified an absenteeism rate and
      also characterized the kinds of absences from work among nursing personel in
      surgical wards of a University Hospital. This investigative study had a
      quantitave, qualitative and retrospective aspect. Data were obtained from January
      to December of 1998. Results showed 29.63% of absences on that period. This total
      is composed by 23.28% of predictable absences and 6.35% of non-predictable
      absences as an index of calculated absenteeism.

PMID- 11998108
TI  - [Leadership and communication: development of a measurement tool for graduating
      nursing students].
AB  - Leadership and communication are themes of importance for the development of
      Nurse's work so that the upbringing of this professional needs to begin in the
      undergraduate course and continue through professional life. The present study
      aimed to identify the knowledge of students of the 4th year of the Nursing School
      of a public University about leadership na communication. In order to achieve
      this goal, the authors elaborated an instrument and submitted it to apparent and
      content validation, pilot test and statistic treatment. Data was collected
      through the application of the instrument to 67 students in October of 1998. The
      analysis of the results indicated that the students showed knowledge about
      leadership and communication, although they did not affirm that what they had
      learned it in the Undergraduate Course about it was enough.

PMID- 11998109
TI  - [Family care for elderly patients with cerebrovascular accident sequelae].
AB  - This study had as objectives to identify the nature of the family care given to
      the elderly with sequels of Cerebral Vascular Accident (AVC); to understand its
      major problems; and to discuss its meaning from the caregiver's vision. It was
      developed through a qualitative/descriptive methodology. The subjects, five
      caregivers of elderly with sequels of Cerebral Vascular Accident, were
      interviewed at their homes. Semi-structured interviews and the projective
      technique (story drawing with a theme proposed by Trinca) were used. The data
      analysis was done through thematic analysis (the first phase of the Enunciation
      Analysis recommended by d'Unrug, in Bardin, 1994) which rose the following
      categories: "nature of the family care"; "social-economic changes of the
      caregiver"; "emotional and physical burnout of the caregiver"; and "the meaning
      of the family care". The results allowed a characterization of the caregivers
      group and the identification of total care to the elderly.

PMID- 11998110
TI  - Council on Economic and General Welfare Committee.

PMID- 11998111
TI  - Male pelvic anatomy/post-prostatectomy incontinence.
AB  - There is an intricate relationship between structure, position, and function
      within the lower urinary tract. To understand the individual problems that may
      occur with post-prostatectomy incontinence, it is necessary to be aware of these
      relationships.

PMID- 11998112
TI  - Valrubicin: an alternative to radical cystectomy for carcinoma in situ of the
      bladder.
AB  - Treatment options for patients who fail BCG therapy are limited. While cystectomy
      may be curative, not all patients can withstand the medical and/or psychologic
      stresses associated with surgery or resection. Valrubicin represents a safe and
      effective second-line intravesical therapy.

PMID- 11998113
TI  - Early catheter removal following radical perineal prostatectomy: a randomized
      clinical trial.
AB  - Radical perineal prostatectomy allows for a watertight closure of the
      urethrovesical anastomosis. This trial determined that early catheter removal may
      be feasible and desirable in patients undergoing radical perineal prostatectomy.
      Early catheter removal can lead to improved patient comfort and well-being.

PMID- 11998114
TI  - A pilot study to determine predictors of behavioral treatment completion for
      urinary incontinence.
AB  - Although a program of pelvic floor muscle exercises augmented with biofeedback is
      a safe, efficacious way to treat urinary incontinence, many patients do not
      finish the program. The only significant predictor of treatment completion in one
      outpatient referral clinic for urinary incontinence was keeping a 7-day bladder
      diary.

PMID- 11998116
TI  - Getting ready for certification: obstructive uropathy and genitourinary trauma.

PMID- 11998117
TI  - New method to treat recurring UTIs discovered.

PMID- 11998118
TI  - Promising new test for early detection of prostate cancer.

PMID- 11998119
TI  - Female sexual dysfunction and potential treatments.

PMID- 11998120
TI  - The diagnosis and treatment of interstitial cystitis.
AB  - Interstitial cystitis is a severe bladder disease of unknown etiology with no
      cure. The diagnosis and treatment of this difficult disease has frustrated both
      patients and clinicians alike. Multimodality therapy is the most effective
      treatment for interstitial cystitis.

PMID- 11998121
TI  - Clinical conversations: nurses who work with patients with interstitial cystitis.
AB  - Nurses who work with patients with interstitial cystitis agree these patients
      demand considerable clinician time. Interstitial cystitis is a chronic disease
      with several etiologic theories explaining the syndrome. Diagnosis and treatment
      are already updated in the preceding article by Dr. Peters. Conversations with
      nurses who practice in different areas of the United States extend this
      discussion by addressing patient issues and offering specific nursing advice.

PMID- 11998122
TI  - Effect of telephone followups on post vasectomy office visits.
AB  - Vasectomies are considered minor outpatient procedures. Yet, many patients return
      to their urologist's office for rechecks because of complications or the need for
      reassurance of normal healing sequela. This study suggests that use of a tool for
      telephone followup can increase patient satisfaction and benefit urologic
      practice by curtailing the incidence of needless followup visits.

PMID- 11998123
TI  - Compliance with pelvic floor exercise program: maintaining bladder symptom
      relief.
AB  - Urinary incontinence can cause social isolation and be a financial and hygienic
      burden to the individual. Pelvic floor muscle exercises can be effective in
      maintaining and improving urinary incontinence and associated bladder symptoms
      following a successful course of biofeedback and electrical stimulation.

PMID- 11998124
TI  - Beyond the bed bath: one nurse's journey.

PMID- 11998125
TI  - Getting ready for certification: obstructive uropathy and genitourinary trauma.

PMID- 11998126
TI  - National association for continence launches nationwide support groups.

PMID- 11998127
TI  - NAFC begins development of continence care guidelines for assisted living
      facilities.

PMID- 11998128
TI  - Creating the forgetting organization.

PMID- 11998129
TI  - Artificial urinary sphincter implantation using a bulbous urethral cuff:
      perioperative care.
AB  - Urinary incontinence is a common problem encountered by clinicians and nursing
      staff. An artificial genitourinary sphincter (AGUS) placed around the bulbar
      urethra or bladder neck has become one of the gold standards for treating urinary
      incontinence due to sphincteric incompetence. It is imperative not only for
      physicians but also the nursing staff to have a working knowledge of the
      mechanics, risks, benefits, and durability of the AGUS to provide care for those
      patients encountered with an AGUS.

PMID- 11998130
TI  - A shortage of minority nurses: a national campaign.

PMID- 11998131
TI  - Resources for working with African American and Hispanic Communities.

PMID- 11998132
TI  - Problems with food packaging: are we promoting mealtime dependence in the
      elderly?

PMID- 11998133
TI  - The pivotal role of nursing in dysphagia management.

PMID- 11998134
TI  - Collaborative research program--rehabilitation & long-term care.

PMID- 11998135
TI  - Empowerment.

PMID- 11998136
TI  - Ureteral J stents: followup is not optional.
AB  - Double J ureteral stents are an example of a commonly used implanted medical
      device. Three case studies illustrate the necessity of good followup care to
      prevent morbidity. This provides an opportunity to devise a proactive system to
      assist in ensuring the proper patient followup care by establishing an efficient
      tracking system.

PMID- 11998137
TI  - Criteria for successful neobladder surgery: patient selection and surgical
      construction.
AB  - The neobladder, an intestinal bladder substitute, allows select patients to void
      naturally through the urethra, and has become an increasingly popular form of
      continent urinary diversion surgery. The criteria for patient selection and the
      principles of surgical construction of the Studer pouch that must be met to
      achieve the best functional results for these patients are outlined.

PMID- 11998138
TI  - Nursing management of neobladder surgery: the Studer pouch.
AB  - Successful results for patients undergoing neobladder surgery demand meticulous
      surgical technique, as well as expert nursing management and patient education.
      Current practice and guidelines developed for the Hospital of the University of
      Pennsylvania for the nursing management of patients undergoing Studer pouch
      surgery are delineated.

PMID- 11998139
TI  - Comparison of behavior therapy methods for urinary incontinence following
      prostate surgery: a pilot study.
AB  - Americans are living longer. As a result, an increased number of pathologic
      prostates are being detected and treated. As a consequence of complications from
      surgical treatment, such as prostatectomy, urinary incontinence may occur.
      However, it is important to understand urinary continence in the male and the
      anatomic changes that result with prostatectomy. Having objective measures that
      are cost-effective and accessible can assist with equaling subjective and
      objective assessments of continence, as well as determining successful outcomes
      and the need for more complex behavioral treatments.

PMID- 11998140
TI  - High-fat diet and prostate cancer: the controversial connection.
AB  - High-fat diet has been associated with conditions such as heart disease and colon
      cancer. Is there a link between high-fat diet and prostate cancer? The summation
      of an abbreviated literature search strives to answer this question.

PMID- 11998141
TI  - Getting ready for certification: voiding and voiding dysfunction.

PMID- 11998142
TI  - From mechanical to integrated organizations: the leader's challenge.
AB  - The leader in a nursing organization, whether it is the nurse manager or the
      nurse executive, is only as good as the positive synergistic relations that are
      developed with all parts of the organization. The converse is also true that the
      leader of any part of the organization is only as good as the synergistic
      relations she/he develops with the nurses and direct caregivers. Synchronicity is
      the mark of an effective organization and the hallmark of integrated
      organizations.

PMID- 11998143
TI  - To place or not to place: making the nursing home decision.

PMID- 11998144
TI  - Linking nurse clinicians to research committees.

PMID- 11998145
TI  - Assisting caregivers of young children exposed en utero to alcohol, crack/cocaine
      and other drugs: a model for intervention.

PMID- 11998146
TI  - History of district 5: from the 1930s through the 1970s.

PMID- 11998147
TI  - History of the Kentucky Nurses Foundation.

PMID- 11998150
TI  - Staying safe in the great outdoors.

PMID- 11998151
TI  - Ardeparin and danaparoid.

PMID- 11998152
TI  - Treating pancreatitis in the acute care setting.
AB  - Acute pancreatitis is associated with significant complications and mortality.
      This article describes the pathophysiology and complications of, and treatments
      for acute pancreatitis, and the nurse's role in caring for a patient in the acute
      care setting.

PMID- 11998153
TI  - Responding to summer emergencies.
AB  - Summer's arrival ushers in health hazards ranging from bee stings to lightning
      strikes. This article discusses preventive measures and provides first aid and
      ongoing care instructions for common summertime emergencies.

PMID- 11998155
TI  - A guide to pediatric fluid replacement and maintenance.
AB  - Use these charts to guide treatment for a dehydrated child.

PMID- 11998154
TI  - Marfan syndrome: a review.
AB  - Cardiac complications of Marfan syndrome can be fatal. This article reviews the
      assessment of a patient with this hereditary disorder, complications and their
      treatment, and nursing care.

PMID- 11998157
TI  - The bearer of bad news.

PMID- 11998156
TI  - Integrating hemodynamic monitoring and physical assessment.
AB  - Pulmonary artery catheters pose significant risks for patients. This article
      describes how nurses can use their detective skills in concert with--or instead
      of--a pulmonary artery catheter.

PMID- 11998158
TI  - Rebuilding the emergency department.
AB  - A nurse-manager of a busy urban emergency department (ED) recounts a $10.7
      million complete renovation and expansion that added close to 20,000 square feet
      to the unit. Advice includes how to plan for security and equipment needs, create
      a design that exceeds expectations, get the ED through the ambitious construction
      phase--and anticipate the personal needs that accompany added responsibility.

PMID- 11998159
TI  - How to bolster nurses' group power.
AB  - Help staff achieve the group power they need to be heard and reach their goals.

PMID- 11998160
TI  - Innovative teaching: read the writing on the wall.
AB  - Need a creative way to stimulate adult learners? Interactive bulletin boards hook
      readers and give nurse leaders an opportunity to communicate with humor.

PMID- 11998161
TI  - The effect of critical care hospitalization on family members: stress and
      responses.
AB  - Family members of intensive care patients may experience stressors that threaten
      both personal health and family integrity. This study found that family members
      endure multiple concurrent stressors and exhibit numerous behavioral responses,
      including changes in eating, sleeping, activity, and family roles and
      responsibilities. Nurses can promote family integrity with interventions that
      address these behavioral changes and promote normal behavior patterns.

PMID- 11998162
TI  - [Theoretical risk of vCJD transmission via blood transfusion. Leukocyte and
      erythrocyte depletion of the transfusion blood is a practice in many countries].

PMID- 11998163
TI  - [Four experts on the proposal to a common European research policy: "More
      responsibility to the EU-administrators"].

PMID- 11998164
TI  - [Mesenchymal stem cells. Basic science and future clinical use].
AB  - Mesenchymal stem cells can be obtained from a bone marrow aspirate taken from the
      iliac crest of adult humans. The cells can be ex vivo expanded to large numbers
      and retain the ability of differentiate to cardiac, bone, adipocytes and muscle
      cells in vitro and in vivo. Undifferentiated mesenchymal stem cells produce large
      numbers of growth factors that control hematopoiesis and modulate lymphocyte
      function. Mesenchymal stem cells are well tolerated when transplanted to humans
      and animals. After transplantation, the differentiation appears to be controlled
      by local factors in the respective tissues. When co-transplanted together with
      hematopoietic cells in a stem-cell transplantation setting, mesenchymal stem
      cells appear to enhance engraftment of the hematopoietic cells as well as reduced
      the incidence and severity of graft-versus-host disease.

PMID- 11998165
TI  - [Ursodeoxycholic acid in the treatment of chronic cholestatic liver disease.
      Documented delay in disease progress inspires hope].
AB  - The effect of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC) has
      been investigated in a large number of randomized controlled studies. Meta
      analyses of these studies have not proved a beneficial effect on survival.
      However, these analyses have also comprised patients with end-stage PBC as well
      as patients with very early PBC. A prolonged survival in such groups of patients
      is not expected to be demonstrated in short-term studies. Modified meta-analyses
      are underway. A number of beneficial effects on the disease process and
      complications still make an optimistic view of the drug in PBC justifiable.
      Limited experience suggests a beneficial effect of UDCA also in other cholestatic
      diseases.

PMID- 11998166
TI  - [Users of ultrasound machines are often subjected to musculoskeletal could be
      preventive measures. Better work organization and equipment could be preventive
      measures].
AB  - Stress, musculoskeletal symptoms, and eye strain are common among users of
      ultrasound machines. The purpose of the study was to identify work situations
      that induce a psychosocial or physical load in work with ultrasound. 12
      sonographers participated. Questionnaire and video-based interviewing methods
      were used. Effects of changes in work organisation and equipment that were
      introduced after the first study were followed up after 6 months (9 of the
      participants in the former study). The study confirmed that musculoskeletal
      symptoms were common. Work situations inducing physical and/or psychosocial loads
      were identified. Changes of the equipment and work organisation led to positive
      effects both in terms of the physical and the psychosocial load. Better work
      organisation and ergonomically designed equipment are measures that can prevent
      work-related disorders.

PMID- 11998167
TI  - [Examination of peripheral sensibility. Vibration test is more sensitive than
      monofilament test].
AB  - Diabetes mellitus is often attended by complications such as neuropathy. A
      standardized examination method can presumably facilitate identification of
      patients with peripheral neuropathy. A study was carried out for the purpose of
      evaluating monofilament examination as a compliment to vibration testing in the
      workup of peripheral sensibility. 236 adult patients, mainly with type-2
      diabetes, were examined by diabetes nurses. These examinations entailed analysis
      of potential variations in correlation between neuropathy, age and duration of
      diabetes. The results showed a difference between the two test methods, with
      vibration testing showing greater sensitivity. There was a clear association
      between neuropathy on the one hand, and both increased age and longer duration of
      diabetes on the other. Even if the monofilament instrument did not show as great
      a sensitivity as tuning-fork/Biothesiometer in this study it should nonetheless
      be used as a complement in the neuropathy workup of the diabetic patient.

PMID- 11998168
TI  - [Recurrent pain in children and parents--no factual evidence of familial pain
      clustering].
AB  - Recurrent pain in children is a universal phenomenon, which occurs in about 50
      percent of all children. The most prevalent pain areas are the stomach, head,
      back and neck/shoulders. A somatic cause of the symptoms is seldom found, but the
      pain is often related to other discomforts, problems or lack of family
      functioning. There has been a common belief that "pain runs in families". In our
      investigation of 358 mother-father-child trios, where the members reported on
      their own symptoms, we found little support for this hypothesis. There is a need
      for further research on these problems, where the study design and measure
      instruments should be carefully validated.

PMID- 11998169
TI  - [Incontinentia pigmenti. A rare disease with many symptoms].
AB  - Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a rare multi
      systemic disorder. The disease is characterised by abnormalities in ectodermal
      tissues including the skin, eyes, central nervous system and dentition. It is
      inherited as an X-linked dominant trait and is usually fatal for male fetuses.
      Thirty-eight Swedish patients from 16 families were identified. Thirty patients
      were examined clinically and their DNA were analysed for deletions in the NEMO
      gene. The disease showed a large clinical variability even within families and
      the common deletion in the NEMO-gene was found present in 70% of the families.

PMID- 11998170
TI  - [Stimulating occupational environment and enough time for consultations result in
      better quality of care].

PMID- 11998171
TI  - [Early history of echocardiography--a pioneering work of Inge Edler].

PMID- 11998172
TI  - [Rorschach test is still used projectively within Swedish forensic psychiatry].

PMID- 11998173
TI  - [Church of Scientology and criticism of ADHD].

PMID- 11998174
TI  - [Leukocyte count and CRP determination in acute appendicitis--does it affect the
      clinical findings?].

PMID- 11998175
TI  - [Time for primary health care services to take the public health science
      seriously!?].

PMID- 11998176
TI  - [Medical disability evaluation--some suggestions].

PMID- 11998177
TI  - [Is rectal palpation without any value in appendicitis?].

PMID- 11998178
TI  - [Private health care in Stockholm is threatened].

PMID- 11998179
TI  - [Unwanted pregnancy and unsafe abortion: 2 health problems that persist in Latin
      America].

PMID- 11998180
TI  - Contraceptive use among Jamaican teenage mothers.
AB  - OBJECTIVE: To compare the prevalence of contraceptive use among teenage mothers
      who were participating, and teenage mothers who were not participating, in a
      program in Jamaica that had been established to deal with the country's serious
      problem of repeat pregnancies among adolescents. METHODS: A historical cohort
      design was used to assess the impact that the Women's Centre of Jamaica
      Foundation (WCJF) Programme for Adolescent Mothers had on contraceptive use among
      the target population of adolescents 16 years and under who had experienced a
      first live birth in 1994. RESULTS: Contraceptive use at first intercourse was
      found to be higher among WCJF program participants (44%) than among
      nonparticipants (37%), but this difference was not significant (P = 0.35).
      Contraceptive use after first live birth was also higher among WCJF program
      participants (94%) than among nonparticipants (86%), and this difference was
      significant (P = 0.04). Contraceptive prevalence at last intercourse (in 1998)
      did not differ between participants and nonparticipants (both 69%). CONCLUSIONS:
      Contraceptive use among this population in Jamaica was highest when the
      respondents' perception of vulnerability to pregnancy was most acute, that is,
      after the first live birth. All adolescents, both males and females, need to be
      educated about the importance of sustained and effective use of contraception in
      order to reduce the risk of unintended pregnancy and sexually transmitted
      diseases.

PMID- 11998181
TI  - [Ongoing, flexible distance learning through the Internet: course on
      decentralized management of human resources in health care].
AB  - This paper describes the Course on Decentralized Management of Human Resources in
      Health Care, which is an Internet-based distance learning program to train and
      provide continuing education for health care professionals. The program is an
      initiative of the Pan American Health Organization, and it was organized in
      response to the growing need for self-reliant professionals who can constantly
      upgrade their knowledge without having to leave their place of work. The proposed
      model promotes an educational process that brings together theory and practice in
      realistic and relevant contexts and that maximizes the participation of students,
      both individually and in groups. The program has been evaluated in pilot studies
      in Brazil, Chile, and Peru. Following these assessments, the course has been
      adapted to facilitate its implementation and to adjust its contents to fit each
      country's circumstances.

PMID- 11998182
TI  - [A mathematical model of the annual risk of tuberculosis infection in Cali,
      Colombia].
AB  - OBJECTIVE: The annual risk of infection (ARI) for tuberculosis is the probability
      that an individual without previous contact with the tubercle bacillus has of
      being infected during the course of a year. The ARI is the most appropriate
      indicator for estimating the degree of tuberculosis infection in a population.
      The objective of this paper was to estimate the ARI and its trends in the city of
      Cali, Colombia, using data provided by the Municipal Secretariat of Health.
      METHODS: We used a deterministic model of the dynamics of pulmonary tuberculosis.
      The flows among the population subgroups were based on the natural history of the
      disease, taking vaccination into account. Using the data from the Municipal
      Secretariat of Health, we estimated the initial conditions and the values of the
      parameters. RESULTS: The mean ARI values were 1.24% in the 1970s, 0.93% in the
      1980s, and 0.85% in the 1990s. In order to assess trends, we attempted to predict
      the annual risk, utilizing a nonlinear least-squares adjustment of the data on
      the overall percentage for each year. With that approach, we projected that the
      ARI in 2003 would be 1.3%, indicating a return to the patterns found in the
      1970s. CONCLUSIONS: The estimated risk of tuberculosis infection in Cali during
      the decades of the 1970s, the 1980s, and the 1990s was very high in comparison
      with the risk in countries such as the Netherlands, which in 1985 had an ARI of
      0.012%. However, the ARI in Cali is not so high in comparison to indices for
      other countries of South America, which range from 0.5% to 1.5%. This model and
      the simulation it produced showed a rising trend in the ARI for Cali, as well as
      demonstrated that the ARI will tend to continue to rise if control measures are
      not improved.

PMID- 11998183
TI  - [Selenium concentration in food consumed in Brazil].
AB  - OBJECTIVE: To determine the selenium content of foods consumed in Brazil.
      METHODS: The project was carried out between 1993 and 1999. The food samples were
      collected in stores in several Brazilian states. The levels of selenium were
      determined by hydride generation atomic absorption spectrophotometry and by wet
      oxidation. RESULTS: The highest levels of selenium were found in animal products,
      especially fish, and in wheat products. We found that plant products generally
      had selenium levels of less than 5.0 micrograms/100 g. CONCLUSIONS: In Brazil a
      diet rich in animal products, especially fish, is important in ensuring
      consumption of the recommended levels of selenium.

PMID- 11998184
TI  - Breast cancer in Latin America and the Caribbean.
AB  - As recently as two decades ago breast cancer was not a significant public health
      concern in Latin America and the Caribbean (LAC). However, mortality rates from
      breast cancer have been increasing for at least 40 years in most LAC countries.
      Socioeconomic development and consequent changes in reproductive behaviors over
      the past 50 years are thought to have contributed to the increased risk of breast
      cancer. Socioeconomic development has also increased women's health awareness and
      therefore the demand for quality services. In industrialized countries, screening
      and widely available, high-quality treatment protocols are being implemented as
      the main strategy for breast cancer control. Studies show that out of three
      available screening methods (mammography, clinical breast examination, and breast
      self-examination), only mammography for women 50-69 years of age has been
      effective at reducing mortality, and has done so by an estimated 23%. While there
      is much controversy about the benefits and cost-effectiveness of mammography
      screening for women aged 40-49, some countries, including Australia, the United
      States of America, and four European nations, recommend that physicians assess
      the need for it on an individual basis. A survey that we conducted of LAC
      countries shows that most of their breast cancer screening policies are not
      justified by available scientific evidence. Moreover, as seen by relatively high
      mortality/incidence ratios, breast cancer cases are not being adequately managed
      in many LAC countries. Before further developing screening programs, these
      countries need to evaluate the feasibility of designing and implementing
      appropriate treatment guidelines and providing wide access to diagnostic and
      treatment services. Given the relevance of breast cancer in Latin America and the
      Caribbean today, it is crucial that both women and health care providers have
      access to up-to-date information on which to base their decisions.

PMID- 11998185
TI  - [Unwanted pregnancy: impact on health and society in Latin America and the
      Caribbean].
AB  - Engaging in sexuality and reproduction should always be something that is wanted
      and planned. Unfortunately, when that is not the case, one result can be unwanted
      pregnancy. Unwanted pregnancies have consequences for women, their families, and
      their countries. This document reviews the causes and results of unwanted
      pregnancy, emphasizing the impact that this problem has on Latin America and the
      Caribbean (LAC). Four reasons why unwanted pregnancy is a continuing problem in
      LAC are: 1) people's growing desire to have smaller families, 2) the unmet need
      for family planning, 3) the fact that contraceptive methods are not 100%
      effective, and 4) unwanted sexual relations. Unwanted pregnancies especially
      affect adolescent women, single women, and women over 40 years of age. Given
      their desperate situation with an unwanted pregnancy, some women opt for an
      unsafe abortion, which can lead to their death. Other women can go so far as to
      commit suicide, or be murdered by a family member or other person who is unhappy
      that the pregnancy has occurred. It has been found that women who decide to
      continue with the pregnancy have higher risks of suffering an illness, and the
      same is true for the child. Reducing unwanted pregnancies and treating post
      abortion complications are key to lowering maternal mortality and morbidity. This
      necessitates developing mass communication programs that address gender issues,
      education programs for girls, and sex education programs. It is also vital to
      make available to all persons reproductive health services that include family
      planning methods. In the countries of LAC with laws that specify grounds for
      legally ending a pregnancy, it is necessary that health care be organized to
      actually provide this service, and that health care programs obtain the safest,
      most effective technologies now available for ending a pregnancy.

PMID- 11998186
TI  - New recommendations from the United States Government on breast cancer screening.

PMID- 11998187
TI  - [HIV/AIDS in the workplace. Practical recommendations of the International Labor
      Organization].
AB  - There are now some 36 million people in the world infected with HIV/AIDS. It is
      estimated that more than 23 million of them are economically active, including
      642,000 persons in Latin America and the Caribbean. In the workplace, HIV/AIDS
      reduces incomes, imposes added costs on companies, and undermines fundamental
      labor laws due to the discrimination and rejection that infected individuals
      suffer. In response, the International Labor Organization (ILO) has produced a
      document entitled An ILO code of practice on HIV/AIDS and the world of work,
      which is summarized in this piece. The ILO document aims to help those in the
      workplace to cope with the HIV/AIDS epidemic through a set of guidelines related
      to: (a) preventing infection, (b) managing and reducing the impact that HIV/AIDS
      has on the workplace, (c) delivering care and support for infected workers and,
      in general, to all the people affected by this epidemic, and (d) eliminating
      discrimination against persons who are infected or are suspected of being
      infected. The ILO Code is intended to help in preparing and adopting specific
      measures in the workplace, thus promoting dialogue and other forms of cooperation
      among the government, employers, workers and their representatives, workplace
      health and safety officers, HIV/AIDS specialists, and other interested parties.
      The intention is also for the Code recommendations to be implemented and
      integrated with national laws, policies, and programs; company or business
      agreements; and workplace policies and action plans. This ILO Code is an
      important step in the struggle against HIV/AIDS. Aimed at governments, employers,
      and workers throughout the world, the Code recommendations constitute a useful
      tool in addressing the problem of HIV/AIDS in the workplace, in a just manner. As
      a "motor" of society, work cannot remain separated from issues of such great
      social impact.

PMID- 11998188
TI  - Health human resource planning for the new millennium: inputs in the production
      of health, illness, and recovery in populations.
AB  - HHRP needs to be sensitive to demographic changes in both population and provider
      groups. Analyses aimed at refining and improving the way in which demographic
      change is incorporated into HHRP will continue to enhance health human resource
      policies. However, the demographic basis of much HHRP fails to consider the
      effects of other changes in society that impact on the need for care in the
      population and the provision of care. In this paper the importance of introducing
      a production-function approach to HHRP has been presented. In some cases,
      existing data may be available to complement the demographic analyses with
      consideration of these broader issues. However, in other cases the ability to
      improve existing approaches will require the collection of new data. Although
      collecting additional data will involve costs, this is the price of improving
      HHRP exercises.

PMID- 11998189
TI  - Nursing matters: the Nursing and Health Outcomes Project of the Ontario Ministry
      of Health and Long-Term Care.

PMID- 11998190
TI  - A survey of Web-based health human resource planning activities in Canada.

PMID- 11998191
TI  - Sense of self: voices of separation and connection in women who have experienced
      abuse.
AB  - The findings of qualitative studies with women who have experienced abuse by an
      intimate partner suggest that a woman's sense of self is a central feature in her
      decision to leave the abusive relationship. This qualitative study was
      undertaken, in part, to listen to how women describe themselves, specifically
      explicating voices of relational connection and disconnection within the
      narratives. This paper presents the findings of interviews with 18 rural women
      from culturally diverse backgrounds who had been or were currently in abusive
      relationships. The women were asked to respond to the question "How would you
      describe yourself to yourself?" The responses were read using the interpretive
      method of reading narratives for self and moral voice. The theory of moral
      development was used to frame the inquiry. The experiences of self that emerged
      from the narratives are presented as progressively relational voices of
      separation and connection. The relationship between these voices and moral
      development is discussed, as are implications for nursing practice and for future
      research.

PMID- 11998192
TI  - The effects of organizational culture on nursing professionalism: implications
      for health resource planning.
AB  - The organizational structure of many hospitals conflicts with the practice of
      professional nursing, adversely affecting patient outcomes. The ability of nurses
      to practise in a professional manner may be influenced by the organizational
      culture of their work environment. Personal attributes may also play a role.
      Patient outcomes depend on the identification and promotion of scarce health
      resources. Personal investment theory was used as the conceptual foundation for
      this study because of its ability to blend environmental context and personal
      behaviours associated with motivation. Secondary data analysis was undertaken to
      determine whether organizational culture and personal sense of accomplishment can
      predict nursing professionalism. Multiple regression analysis showed that
      organizational culture predicted over 16% of the variance in nursing
      professionalism. Therefore, nursing professionalism and hospital environment
      featuring a strong organizational culture are two health resources that can
      promote improved patient outcomes.

PMID- 11998193
TI  - Nurses begin a national plan for the integration of supportive care in health
      research, practice, and policy.
AB  - The demand for and use of health, social, and other human services is related not
      to the type or severity of disease but rather to a person's socio-economic,
      cognitive, and emotional characteristics and environmental circumstances. A
      workshop on supportive care was held to promote a robust research environment,
      the creation of new knowledge, the setting of an integrated health research
      agenda, a focusing of attention on the evolving health-care system, and
      anticipation of emerging health challenges. While the workshop was intended to
      address a research mandate for the Canadian Institutes of Health Research, a
      larger vision emerged, to include advocacy, information system, surveillance, and
      policy development required by institutional, community, voluntary, private
      sector, family caregiver, and provider systems. The development of a national
      supportive care strategy will enable Canadians with disease and disability to
      live with all of their challenges, and could engage researchers, clinicians,
      advocacy groups, and people experiencing major health challenges.

PMID- 11998194
TI  - Recruitment of community-dwelling older adults for nursing research: a
      challenging process.
AB  - In the face of changing demographics, the need for gerontological nursing
      research has become central to the development of relevant health and social
      policies and resources for older adults. The recruitment of community-dwelling
      older adults presents multiple challenges for the nurse researcher wishing to
      conduct meaningful research. A common concern cited in the literature is the
      recruitment of sufficient numbers of older participants. The recruitment of
      persons 65 years of age and older is influenced by factors such as gender and
      study design as well as physical, social, psychological, and age-related changes.
      This paper describes these factors, as well as effective strategies for
      recruiting older adults, the authors' conceptualization of a 3-phase recruitment
      process, and key points for the nurse researcher to consider when recruiting
      subjects.

PMID- 11998195
TI  - Where to from here?
AB  - Although this conceptual framework is easy to understand, the data requirements
      for the mathematical model that underpins the framework are complex and must be
      defined carefully. In our framework, simulations of the health system are used to
      provide needs-based estimates that are aimed at optimizing outcomes. This type of
      model builds on research conducted at the macro, meso, and micro levels in order
      to reflect the complexity of relationships in the health human resource process.
      The papers in this issue of the Journal provide insight into specific constructs
      of the model. At the macro level, Tomblin Murphy explores methodological
      challenges in HHRP research. She examines common assumptions and the validity of
      their use in modelling in all aspects of the proposed framework. Tourangeau and
      colleagues report on the impact of hospital nurse-staffing decisions on 30-day
      mortality rates. Their model adds to our knowledge of the relationships among the
      management, deployment, and utilization of nursing services and
      patient/population outcomes. Shamian and colleagues explore the relationship
      between hospital-level indicators of the work environment and aggregated
      indicators of health and well-being for registered nurses employed in acute-care
      hospitals in the province of Ontario. This paper contributes to our understanding
      of how management decisions regarding the work environment influence nurse
      outcomes. Manojlovich and Ketafian explore the conflict between the practice of
      nursing and the organizational structure of many hospitals. This study provides
      insight into the management aspects of how the work unit is organized and the
      process of care delivery. Zboril-Benson examines the reasons for nurse
      absenteeism in the province of Saskatchewan. Birch describes the need for the
      planning process to take into account demographic changes in both populations and
      provider groups. A major challenge in modelling health human resources is access
      to meaningful databases for planning purposes. Pringle describes a unique Ontario
      initiative currently underway to develop and validate a nurse-sensitive set of
      data that will be routinely collected and will enhance HHRP in that province.
      Since the science that underpins HHRP is complex and rapidly changing, few books
      have been written on the subject. Reflecting the dynamic nature of the science,
      Tomblin Murphy and Barrath provide an excellent review of "grey literature" and
      useful Web sites for those interested in HHRP.

PMID- 11998196
TI  - A hospital-level analysis of the work environment and workforce health indicators
      for registered nurses in Ontario's acute-care hospitals.
AB  - The purpose of this study was to explore the relationship between hospital-level
      indicators of the work environment and aggregated indicators of health and well
      being amongst registered nurses working in acute-care hospitals in Ontario,
      Canada. This ecological analysis used data from a self-reported survey instrument
      randomly allocated to nurses using a stratified sampling approach. Multivariable
      linear regression models were used to examine hospital-level associations for
      burnout, musculoskeletal pain, self-rated general health, and absence due to
      illness. The unit of analysis was the hospital (n = 160), with individual nurse
      responses (n = 6,609) aggregated within hospitals. After controlling for basic
      differences in nurse workforces, including mean age and education, higher
      (better) work-environment scores were found to be generally associated with
      higher health-indicator scores, while a larger proportion of full-time than part
      time nurses was found to be associated with lower (poorer) health scores. This
      study may provide direction for policy-makers in coping with the recruitment and
      retention of nursing staff in light of the current nursing shortage.

PMID- 11998197
TI  - Methodological issues in health human resource planning: cataloguing assumptions
      and controlling for variables in needs-based modelling.
AB  - Health Human Resource Planning (HHRP) models approximate future nursing
      requirements based on a variety of factors specific to the model being employed.
      There is an urgent need to develop a better understanding of the sources of bias
      in statistical modelling in order to ensure that we are guided by accurate and
      robust formulae. This paper addresses these issues as they apply in the context
      of needs-based HHRP research for nursing by presenting a review and discussion of
      the relevant literature as it relates to: (1) the testing of assumptions, (2)
      avoiding ecological and atomistic fallacies, (3) how need is directly or
      indirectly related to health care, and (4) alternatives to aggregate analysis for
      assessing the relationship between health needs and utilization of nursing
      services. The paper concludes that multilevel modelling is useful for the
      simulation analysis of individuals and their ecologies, and that small area
      variation modelling holds promise for assessing the relationship between health
      needs and utilization of nursing services.

PMID- 11998198
TI  - Nursing-related determinants of 30-day mortality for hospitalized patients.
AB  - The purpose of this study was to further our understanding of the effects of
      nursing-related hospital variables on 30-day mortality rates for hospitalized
      patients. A retrospective design was used to test the proposed 30-Day Mortality
      Model. The sample consisted of 75 acute-care hospitals in the province of
      Ontario, Canada. To develop hospital mortality rates, 46,941 patients discharged
      from these hospitals who had a most responsible diagnosis of acute myocardial
      infarction, stroke, pneumonia, or septicemia were included. To develop hospital
      level nursing predictor variables, 3,998 responses to the Ontario Registered
      Nurse Survey of Hospital Characteristics were also included. The findings support
      a relationship between lower 30-day mortality and 3 predictors: a richer
      registered nurse skill mix, more years of experience on the clinical unit, and
      reported larger number of shifts missed. These findings can be used to predict
      the effects of hospital changes in nursing skill mix and years of RN experience
      on patient mortality.

PMID- 11998199
TI  - Why nurses are calling in sick: the impact of health-care restructuring.
AB  - Absenteeism among registered nurses is a major concern for employers; it is
      costly and results in decreased standards of care. Despite the international
      interest in and research on absenteeism, there is relatively little cumulative
      knowledge regarding its determinants. This quantitative, non-experimental study
      profiled the reasons for absenteeism in a random sample of 2,000 front-line
      nurses in the Canadian province of Saskatchewan. Absence was defined as time away
      from work excluding holidays, strike, or layoff. Major causes of absenteeism were
      identified, including minor ailment and fatigue related to work overload. A total
      of 450 respondents had seriously considered leaving the nursing profession, with
      50.4% citing overwork and stress as the primary causes. Higher rates of
      absenteeism were found to be associated with lower job satisfaction, longer
      shifts, working in acute care, and working full-time. Moderate job
      dissatisfaction was found to be associated with longer shifts and working in
      acute care. In light of the current nursing shortage, strategies for reducing
      absenteeism and increasing job satisfaction are warranted.

PMID- 11998200
TI  - [Differential diagnosis of chronic pain syndromes of the musculoskeletal system-
      coding according to ICD-10].
AB  - Primary care for patients suffering from chronic pain is regularly provided by
      either family physicians or inpatient medical wards. A delay in initiating
      specific pain treatment is associated with poor outcome in terms of pain
      intensity, work disability and diminished quality of life. We present a
      diagnostic classification scheme for chronic pain disorders following the
      biopsychosocial disease model. This classification may help primary care
      providers initiate appropriate treatment early in the course of chronic pain, and
      aid in referral of their patients to services familiar with the treatment of
      chronic pain. Given increasing requests for quality control in health care and
      for transparency in disease management by health insurance companies, we propose
      a coding system of chronic non-malignant pain syndromes with the ICD-10.

PMID- 11998201
TI  - [Differential therapy of chronic pain syndromes of the musculoskeletal system in
      primary health care].
AB  - For treatment of chronic non-malignant musculoskeletal pain syndromes to be
      successful, simultaneous medical and psychosocial interventions are required. We
      provide different treatment options for chronic pain disorders for the primary
      care physician who is not a trained psychotherapist. We stress that the physician
      must adopt a particular therapeutic attitude towards his patient. We further
      emphasize the elaboration of a biopsychosocial disease model with the patient,
      cognitive-behavioral interventions, treatment of associated sleep disorders, the
      use of a rational drug therapy regimen, physical therapy, relaxation techniques,
      and involvement of the social environment. Such treatment strategies may help
      primary care physicians to treat their patients suffering from chronic pain more
      successfully and with greater patient satisfaction.

PMID- 11998202
TI  - [Can communication centers have a positive influence on coping with illness?].
AB  - How the subjective conditions of coping can be improved by new information
      technologies like Medicine Call Centers? The solution of this question is the
      basic purpose of the article on hand. The historical genesis and the most
      important differentiations of coping research and how state of the art
      communication technology and its organisation works, will be briefly presented.
      Founding on this report and additionally emphasizing and including the work of
      Badura (1985, 1987, Badura et al. 1997, 1999) one has to concern that the coping
      of sickness under hospitalized conditions can be improved by supporting
      influences named antistressors. Communication in the hospital can work as an
      antistressor. Considering the discussed results and using the possibilities of
      new communication technologies at last an appropriate model will be developed
      which is based on a call center.

PMID- 11998203
TI  - [Sildenafil in erectile dysfunction].

PMID- 11998204
TI  - [Cough and dyspnea during exertion 14 days after nicotine use].

PMID- 11998205
TI  - [Prenatal diagnosis: how to manage this progress?].

PMID- 11998206
TI  - [New physiological, diagnostic and therapeutic concepts in the management of
      rectoceles in women].
AB  - Anterior rectocele is not only a herniation of the anterior rectal wall into the
      vagina, but rather a complex anatomical and functional abnormality which may be
      isolated or associated with other pelvic floor disorders. It could result in
      rectal obstruction with dyschezia, manual extraction of feces, and fecal or gas
      incontinence. The purpose of this review is to describe and to assess the most
      useful methods for the diagnosis and for the treatment of the rectocele. Data
      from physical examination may be improved by defecography. Surgery remains the
      main treatment: several surgical ways (perineal, anal, abdominal, laparoscopic)
      are described. Analysis of the anatomical and functional results allows to assess
      these techniques and to determine the best therapeutic option.

PMID- 11998207
TI  - [Fertility after ectopic pregnancy: the population-based register of the urban
      area around Lille, Northern France].
AB  - The aims of this work were the evaluation of the reproductive outcome after
      ectopic pregnancy, and the assessment of the role of infertility risk factors and
      treatment's strategy. All patients in the population-based register of the urban
      area around Lille, Northern France, were followed-up. 345 women treated between
      April 1994 and March 1997, who were trying to become pregnant were interviewed by
      telephone every 6 months and then every year. The cumulative pregnancy rates were
      calculated by the Kaplan-Meier estimation. Associations between infertility risk
      factors and intrauterine pregnancy were tested by the logrank test, and by a Cox
      model for multivariate analysis. The mean duration of follow-up was 22 months,
      and 228 (66%) women had obtained a new pregnancy at the time of the analysis. 23
      (10%) of the first pregnancies were recurrences. For women for whom EP occurred
      with an IUCD (17 patients), the 1 year intrauterine pregnancy (IUP) reached 67%.
      For the others, the 1 year IUP rate was 56%, and reached 67% after 2 years. After
      adjusting factors associated with fertility with a Cox regression, 3 factors
      seemed to lower reproductive performances: age > 35 years, previous history of
      infertility, and anterior tubal damage. More than half the women treated for EP
      obtained spontaneously a normally progressive pregnancy after 1 year.
      Reproductive performances are associated with characteristics of the patients,
      but do not depend on radical or conservative treatment.

PMID- 11998208
TI  - [Hyperemesis in the first trimester of pregnancy: role of biological
      hyperthyroidism and fetal sex].
AB  - OBJECTIVES: Our objectives were to link hyperemesis gravidarum with biochemical
      hyperthyroidism and hormonal modification (HCG and estradiol) and to test the
      hypothesis that biological abnormalities (ionogram and liver enzyme) are more
      often reported in hyperemesis gravidarum with biochemical hyperthyroidism. STUDY
      DESIGN: Thirty three patients admitted in "Hopital Jeanne de Flandre" with
      hyperemesis gravidarum were studied prospectively. RESULTS: Twenty-two patients
      (66.7%) had biochemical hyperthyroidsm (suppressed thyroid stimulating hormone or
      increased triiodothyronine index or tetraiodothyronine index). Hyperthyroid
      patients were more likely than euthyroid patients to have abnormal electrolyte
      levels (16/22 [72.7%] vs 3/1 [27.3%], P < 0.02) or increased liver enzyme levels
      (8/22 [36.4%] vs 3/11 [27.3%]). The severity of hyperemesis was found to vary
      directly with the degree of hyperthyroidism. We report a female predominance
      among the offspring of mothers with hyperemesis gravidarum. CONCLUSION: Our
      results are suggestive of the involvement of hyperthyroidism and fetal sex in the
      pathogenesis of hyperemesis gravidarum. Also these hypothesis are not clearly
      understood, human chorionic gonadotrophin occurred in the two mechanisms.

PMID- 11998209
TI  - [Cytological history of 148 women presenting with invasive cervical cancer].
AB  - OBJECTIVES: The aim of this study was to analyse the cytological history of women
      presenting with invasive cervical cancer. MATERIAL AND METHODS: Retrospective
      study of 148 patients treated for invasive cervical cancer in three hospitals of
      the North Pas de Calais in France. RESULTS: The average age of patients was 49
      (26-86). Squamous carcinomas represented 81% of cases (120/148), adenocarcinomas
      17% (25/148) and adenosquamous carcinomas 2% (3/148). 36.5% of patients (54/148)
      had never had a Pap smear. 34.5% (51/148) had had an occasional Pap smear (the
      last one dated of more than three years). 8.1% (12/148) were lost for follow up
      after a positive Pap smear. 3.4% (5/148) were treated for cervical dysplasia less
      than three years before the diagnosis of the cervical cancer. 17.5% (26/148) had
      had a Pap smear reported as negative less than three years before the diagnosis
      of the cervical cancer. In this last group, squamous carcinomas represented 57.7%
      of cases (15/26), adenocarcinomas 38.5% (10/26) and adenosquamous carcinomas 3.8%
      (1/26). 18 Pap smears of 26 reported as negative less than three years before the
      diagnosis of the cancer were reviewed. These Pap smears came from 11 patients
      presenting with squamous carcinoma and seven other presenting with
      adenocarcinoma. After review, 15 Pap smears were reported as false negatives and
      two as true negatives. The review was not possible in one case. CONCLUSION: In
      this study, the failures of cervical cancer screening were essentially attributed
      to the lack or the insufficiency of screening and the existence of false
      negatives of the cytology.

PMID- 11998210
TI  - [Heterotopic pregnancies: 8 cases].
AB  - Heterotopic pregnancy is the combination of intra-uterine pregnancy and ectopic
      pregnancy in the same patient whatever is the localization of the ectopic
      pregnancy. The aim of this work was to summarize the epidemics and clinical
      factors, the diagnostic means and the therapeutic methods for the spontaneous
      heterotopic pregnancy in Moroccan context. In a period of 6 years (1993-1998), 8
      patients were treated for heterotopic pregnancy in Lalla Meryem Maternity of
      Casablanca, with a rate of 0.2/1000. Patients' ages ranged from 19 to 37. The
      backgrounds were: abortions (4 cases), secondary sterility (2 cases) and genital
      infection (2 cases). Five patients consulted for metrorrhagia associated with
      pelvic pain. Two for pelvic pain and one for metrorrhagia. The diagnosis was
      confirmed before echography in 5 cases. All patients were operated on, 3 in a
      condition of haemorrhagic shock. Ectopic pregnancy lay at the level of the
      fallopian tube in 7 cases and at the level of the ovary in one. The treatment
      consisted of a salpingectomy in the 7 patients with tubal localisations, the
      ovary pregnancy benefited from ovariectomy. Evolution has been marked by
      expulsion of intra-uterine pregnancy in 6 cases. Two women were able to carry out
      their pregnancy. Heterotopic pregnancy is more and more frequent because of
      genital infection increase and especially the wide diffusion of the assisted
      medical procreation.

PMID- 11998211
TI  - [What kind of support do couples expect when undergoing IVF treatment? Study and
      perspectives].
AB  - OBJECTIVES: To assess the management of the supportive aspects of treatment for
      couples having attempted an in vitro fertilization treatment. MATERIAL AND
      METHODS: Three groups of couples were contacted by questionnaire (successful
      treatment, unsuccessful treatment treatment, outcome still unknown). RESULTS: 48%
      considered it necessary to offer psychological support after the diagnosis. 80%
      considered it difficult to have a thorough representation of the physical aspects
      of an In Vitro Fertilization treatment but mostly they were surprised by their
      lack of an accurate emotional representation. All couples expected an
      availability and receptiveness from the infertility team but the unsuccessful
      treatment group was less satisfied and felt significantly (P < 0.001) less well
      supported. The most difficult moments mentioned were the numerous moments of
      waiting and the announcement of the final result. Emotional support was regularly
      provided by the nurses but 20% wanted psychological counselling. Two thirds of
      all couples considered that a psychological follow-up should be proposed to
      couples for whom the treatment remain unsuccessful. CONCLUSIONS: Results show the
      need for better emotional preparation of couples. As for the emotional support
      during treatment, the need for psychological counselling appears after the
      diagnosis of infertility as well as a constant demand of availability and empathy
      on behalf of the team. Post-treatment counselling may be particularly important
      also. Failure as well as lack of support at that time seemed to colour the way
      couples regard the whole support provided during treatments.

PMID- 11998212
TI  - [Treatment of a case of ovarian cysts in a patient known to have endometriosis].
AB  - Endometrioma is one of the most frequent localisations of endometriosis. The
      diagnosis is based mainly on the intravaginal ultrasonography which has a good
      predictive value, even if there are a lot of atypical echographic aspects.
      Endoscopic surgery remains the standard treatment for endometriosis, the goal
      being the complete removal of the lesions. Three surgical options are possible:
      intraperitoneal cystectomy, the three-phase "Donnez technique" in three time, and
      ovariectomy. Treatment of recurrences of endometriosis must be based on a precise
      diagnosis, and also on the type of patient being treated: patient wishing to be
      pregnant, patient under medically-assisted reproductive programs, and patients
      close to menopause. The ultrasound-guided puncture could be an interesting option
      for multioperated patients or patients under assisted reproductive programs, yet
      these patients should be informed of the high risk of further episodes of
      endometriosis after such a puncture.

PMID- 11998213
TI  - [Toxoplasmosis and pregnancy: current trends in serological follow-up].
AB  - Prevention of congenital toxoplasmosis is based on serological follow-up of
      pregnant patients. Routine serology includes search and titration of specific IgG
      and IgM. In presence of specific IgM, complementary tests should be carried out
      for a better dating of the contamination. Among them, the avidity test is the
      most currently used. It allows to exclude a recent infection in the majority of
      the cases. For difficult cases, it is useful to contact a specialized laboratory.

PMID- 11998214
TI  - [Endometrial hyperplasias resistant to progestins: alternatives to traditional
      treatments].
AB  - Endometrial hyperplasias are mainly regarded as a response to unopposed
      endogenous estrogenic stimulation and concern 12% of perimenopausal women. They
      are usually diagnosed because of irregular bleeding. They are divided into two
      categories based on the presence or absence of cytological atypia and further
      classified as simple or complex according to the extent of architectural
      abnormalities. Endometrial hyperplasias with cytological atypia are classically
      treated by hysterectomy. Endometrial hyperplasias without cytological atypia are
      classically treated by progestins. The bad observance (25% spontaneously
      stopping), the 30% recurrence rate after stopping progestin and the 12-53%
      resistance rate to treatment lead to propose a second-line therapy after
      endocrinological check-up, exploration of haemostasis, pelvic ultrasonography,
      hysteroscopy and endometrial biopsies. Standard treatments include uterine
      curettage which is not very effective and hysterectomy. Medical alternatives
      (gonadotropin-releasing hormone agonists, levonorgestrel-releasing intrauterine
      device) and surgical alternatives (endometrial resection, thermal balloon
      endometrial ablation) were developed to avoid treating functional pathology
      radically. These conservative procedures correct 80% of endometrial hyperplasia
      symptoms with a low rate of lateral effects. However, these results need to be
      confirmed by long-term studies. Some economical, legal or material factors can
      also limit carrying out the procedures. Clinical trials need to be performed to
      better define the place of medical and surgical alternatives to hysterectomy in
      the treatment of endometrial hyperplasias resistant to progestins.

PMID- 11998215
TI  - [Inhibin B is a good marker of ovarian follicular reserve].

PMID- 11998216
TI  - [Inhibin B is not a good marker of ovarian follicular reserve].

PMID- 11998217
TI  - [Osteoporosis in menopausal women and in patients treated with corticoids:
      diagnostic methods and indications (April 2001.) Abridged version].

PMID- 11998218
TI  - [Reflections on the use of obstetric echography].

PMID- 11998219
TI  - [Acute pharyngotonsillitis].
AB  - The article reviews rent findings on the acute pharyngotonsilitis. In the
      aetiology of the disease viral infections prevail. In the bacterial aetiology of
      the acute pharyngotonsilitis mainly group A streptococci predominate. Individual
      types of pharyngotonsilitis are specified, and their typical clinical symptoms,
      diagnostics and therapy are given.

PMID- 11998220
TI  - [Carbonyl stress and chronic renal failure].
AB  - Pathogenesis of many diseases and their complications is linked to oxidative
      stress. In the last two years, the attention has been paid also to carbonyl
      stress which is alosely related to oxidative stress. Carbonyl stress is
      characterized as an increase of reactive carbonyl compounds caused by their
      increased formation and/or decreased breakdown and excretion. Reactive carbonyl
      compounds can be formed from carbohydrates, lipids and amino acids both by
      oxidative and non-oxidative pathways, can be detoxified by several enzymes and
      excreated by kidneys depending on their function. Carbonyl compounds can form
      advanced glycation end-products (AGEs) and advanced lipoperoxidation end-products
      (ALEs), which are known to take part in the pathogenesis mainly of diabetic and
      uremic complications.

PMID- 11998221
TI  - [ABO/H blood groups and factor V Leiden].
AB  - BACKGROUND: Jick and his co-workers published in 1969 an observation showing the
      prevalence of blood group 0 being lower in people with thrombosis than in the
      healthy population. During the next years this finding was several times
      confirmed. The aim of our work was to answer the question on the distribution of
      blood groups in individuals with thrombophilia compared to the control group and
      whether the non-0 blood group increases the thrombosis risk in factor V Leiden
      carriers. We were also interested in mean values of the ProC Global test in
      different blood groups. METHODS AND RESULTS: Factor V Leiden, prothrombin
      mutation 20210A and ProC Global were examined in individuals with thrombophilia.
      The blood group distribution was compared in thrombophilia and control groups.
      The distribution was statistically different (p = 0.000). The mean value of ProC
      Global in the non-0 carriers was lower than in persons with blood group 0.
      CONCLUSION: There is a 1.76 times higher thrombosis risk (1/0.5697 = 1.76) in
      factor V Leiden carriers with blood group non-0 compared to blood group 0. The
      ProC Global mean values differ in patients with blood group 0 and in non-0
      persons.

PMID- 11998222
TI  - [Contradictory results of passive hemagglutination and immunoenzyme tests in the
      determination of specific immunoglobulin G in the serodiagnosis of lues].
AB  - BACKGROUND: With continuing automatization it comes into consideration, which
      tests should be a part of the syphilis screening. Trying to learn more about the
      correlation and comparability of passive hemaglutination and imunoenzymatic
      assay, which are the candidate reactions on the screening test, we analyzed
      results of the above mentioned reactions in 2319 serum samples sent for
      diagnostics of syphilis. Special attention was paid to sera with contradictory
      results in both tests. METHODS AND RESULTS: When results were contradictory the
      patient's probability of having syphilis and the intensity of the reaction were
      analysed. Out of 2319 sera samples examined for syphilis 141 (6.1%) specimens
      belonging to 125 patients were found to provide contradictory results in passive
      hemagglutination (TPHA) and immunoenzymatic assay for the specific
      immunoglobulins G (ELISA IgG). In 14 cases (children of syphilitic mothers) only
      the passively transferred antibodies were found and these samples were excluded
      from the examined group. Almost four fifths of contradictions (88 out of 111,
      i.e. 79.3%) were based on the positivity of TPHA with the negativity of ELISA IgG
      and one fifth only (23 specimens, i.e. 20.3%) concerned the positivity of ELISA
      IgG with the negativity of TPHA. The relation to syphilis was more obvious in the
      TPHA-positive patients: in 88 TPHA-positive patients the syphilitics were
      relatively more common (39 syphilitics, i.e. 44.3%) than in 23 ELISA-positive
      patients (5 syphilitics, i.e. 21.7%), the difference is statistically significant
      (p < 0.05). CONCLUSIONS: It is concluded that TPHA seems to be more sensitive,
      whereas ELISA IgG more specific.

PMID- 11998223
TI  - [Safety of long-term administration of conventional amphotericin B in oncology
      patients].
AB  - In cancer patients with persistent fever and neutropenia, amphotericin B is
      administered for the early treatment and prevention of the clinically occult
      invasive fungal infections. The major drawback of the conventional amphotericin B
      is its nephrotoxicity. We have previously showed that massive potassium, sodium,
      and magnesium supplementation, which corresponds to the amount lost in kidney
      during amphotericin B administration, as well as vigorous hydration, can markedly
      reduce nephrotoxicity of conventional amphotericin B. Clinical courses of four
      oncological patients treated with conventional amphotericin B suspected or proven
      fungal infection for a period of 24 days (two patients), 39 days, and 47 days are
      described. During the long-term amphotericin B administration with
      nephroprotective measures, no severe renal function decrease was observed in any
      of our patients. Massive ion supplementation corresponding to the amounts lost in
      kidney, as well as the vigorous hydration are effective in the prevention of the
      renal function decrease induced by the long-term conventional amphotericin B
      therapy.

PMID- 11998224
TI  - [The Institute for Circulatory Disorders. 1951-1971].
AB  - Investigation of causes, pathogenesis, therapy and prevention of the most
      frequent circulatory diseases has been the key task of the Institute for
      Cardiovascular Research founded in 1951. The Institute's Working groups were
      created accordingly: Arterial hypertension (headed by Jan Brod), Coronary heart
      disease (Vilem Ganz), Arteriosclerosis (Tibor Zemplenyi), Higher nervous activity
      in relation to circulation (Walter Ehrlich), Disturbance in the circulatory
      regulations (Zdenek Fejfar). Rheumatic heart disease, disturbed function of the
      kidneys and of the electrolyte metabolism and peripheral vascular disease were
      also of the clinical interest. The care of patients was the indispensable basis
      for clinical research. Consisted of the clinical department with 80 beds, large
      outpatient department, RTG, ECG, biochemical and haematological laboratories.
      Research projects originated from clinical problem investigated primarily in man.
      Animal experiment was used only in the solution on man proved not possible.
      Within a couple of years the Cardiovascular Research Institute became well known
      abroad and one of the leading clinical centres in Czechoslovakia.

PMID- 11998225
TI  - Taking centre stage. Interview by Nick Lipley.

PMID- 11998226
TI  - Therapy that works.

PMID- 11998227
TI  - Burning issue.

PMID- 11998228
TI  - Bitter sweet epidemic.

PMID- 11998229
TI  - On the streets. Interview by Mary Hampshire.

PMID- 11998230
TI  - It's not so tough being a professional in the peaceful UK.

PMID- 11998231
TI  - A nurse who walked the talk. Interview by Peter Cross.

PMID- 11998232
TI  - Research notes.

PMID- 11998233
TI  - Money for nothing.

PMID- 11998234
TI  - This could catch on.

PMID- 11998235
TI  - Riding into action.

PMID- 11998236
TI  - Too much, too soon.

PMID- 11998237
TI  - Speaking as one.

PMID- 11998240
TI  - Nurses in research: the treatment of acne.
AB  - Many nurses undertake research, either as part of a research team or
      independently as the research lead. Nurses are well placed to participate in
      research, using their clinical skills to the benefit of both the participants and
      the research objectives. This article focuses on the value of nurses in research.
      Using the example of their own experiences of a large NHS clinical trial, the
      authors demonstrate how nurses can become involved in research, what skills are
      needed, and how nursing skills and experience can contribute to the role of a
      clinical assessor/research nurse.

PMID- 11998241
TI  - Improving haematology care in Wales.
AB  - Care for patients with a malignant haematological disorder in Wales has been
      revised significantly since the mid-1990s. Recommendations from expert groups
      stated that a uniformly high standard of care should be provided as close to the
      patient's home as possible and variations in practice that had been causing
      concern and distress to patients and their families be reduced. The All Wales
      Haematology Nurses Group was established to promote and disseminate standards and
      guidelines that would contribute to achieving these aims. The basis for the
      group's work was transformational leadership and collaborative practice. Work is
      ongoing and the group is planning to consolidate achievements to date through
      country-wide audit and professional education.

PMID- 11998242
TI  - Crohn's disease: an overview.
AB  - Crohn's disease is a chronic inflammatory condition that can affect any part of
      the gastrointestinal tract from mouth to anus. In this article, Chris Metcalf
      examines the clinical features, investigations, medical treatment and surgical
      management, as well as the psychological aspects, of the disease.

PMID- 11998247
TI  - Diffusion tensor brain imaging and tractography.
AB  - Diffusion-tensor MR imaging is a promising tool to evaluate white-matter
      integrity by quantitative and graphic maps including neural fiber tractogram.
      Current challenges afoot are to obtain higher quality diffusion-weighted MR
      images (high SNR, isotropic voxel, and high spatial resolution), to create a
      robust mathematical framework to process the data, to construct a user-friendly
      computer-based algorithm, to reveal determinants of diffusion process, and to
      establish analytical methodology.

PMID- 11998248
TI  - Diffusion imaging in brain tumors.
AB  - Diffusion-weighted imaging is of limited value in the MR imaging diagnosis of
      various tumor pathologies, except in differentiating between dermoids/epidermoids
      and arachnoid cysts. Diffusion tractography, on the other hand, allows accurate
      depiction of important white-matter tracts adjacent to brain tumors. This
      technique uses data derived from diffusion tensor imaging.

PMID- 11998249
TI  - Diffusion-weighted imaging of the spinal cord.
AB  - Spinal cord DWI may be useful in providing information not available with
      conventional MR imaging. More work, however, is required to explain what the
      qualitative and quantitative results actually represent. Computer simulations and
      detailed radiologic-histologic correlations will therefore be necessary.

PMID- 11998250
TI  - Diffusion-weighted imaging of the spinal column.
AB  - Diffusion-weighted imaging of the musculoskeletal system including the spine is a
      new MR imaging method. Several studies have shown significantly different
      diffusivities for various pathologic conditions such as edema and tumor. The
      specificity of diagnosis may be increased and therapeutic effects may be
      monitored. Diffusion-weighted sequences especially have been shown to be an
      additional tool for differentiating vertebral fractures caused by osteoporotic
      collapse with bone marrow edema and metastatic collapse. Inclusion criteria
      should include: (1) unknown reason for the vertebral collapse, (2) lack of
      sclerosis, and (3) no prior therapy. Patients with trauma or treated metastases
      may exhibit different signal intensities. In general, those patients do not pose
      problems in differential diagnosis. New sequence developments and higher magnetic
      field gradients should be able to increase spatial resolution and decrease
      problems from motion artifacts. Studies with larger patient groups and sequences
      that quantify the results with ADCs are the necessary next steps.

PMID- 11998251
TI  - High b-value diffusion imaging.
AB  - Perhaps one of the greatest benefits of the development of high b-value
      technology has been the insight provided into the physiologic basis of diffusion
      imaging. The multiexponential features of the diffusion process are revealed on
      scans obtained with high b-value. The subsequent isotropic diffusion images have
      the distinct advantage of more accurately reflecting the intrinsic ADC of the
      tissues examined. This feature has the potential to facilitate clinical
      diagnosis. The degree to which this is proved to be clinically relevant is
      dependent on future investigation, but initial results are promising. The
      clinical potential of high b-value imaging at higher field strength remains to be
      explored. The greater signal to noise afforded by the use of 3-T scanners will
      likely make higher b-value imaging more practical with less costly scan time
      penalties necessary at lower field strengths.

PMID- 11998252
TI  - Diffusion MR imaging of acute ischemic stroke.
AB  - Diffusion MR imaging provides unique information about the physiologic state of
      ischemic tissue. It is highly sensitive and specific in the detection of acute
      and hyperacute ischemic stroke and has greatly improved the diagnosis and
      treatment of acute stroke. The DWI abnormality provides information about
      clinical outcome and final infarct size. Diffusion combined with perfusion MR
      imaging provides information about the operational ischemic penumbra and final
      infarct size. Diffusion MR imaging seems to be promising in the evaluation of
      candidates for thrombolysis.

PMID- 11998253
TI  - Diffusion imaging in neonates.
AB  - Diffusion imaging is a useful technique for the evaluation of many normal and
      pathologic processes occurring in the neonate and often provides complementary
      information for conventional MR and other imaging techniques.

PMID- 11998254
TI  - Diffusion imaging in multiple sclerosis.

PMID- 11998255
TI  - Was fired nurse victim of unfair labor practice?

PMID- 11998256
TI  - Does your code blue team have immunity? Case on point: Tucker v. County of Los
      Angeles, 2001 WL 1215868 P.2d-CA.

PMID- 11998257
TI  - MO: dialysis needle "misplaced" in pt.'s arm: did nurse deliberately stab
      "inmate?".

PMID- 11998258
TI  - MN: NLRB orders "bargain with steel workers:" court remands case to NLRB on
      supervision issue.

PMID- 11998259
TI  - Unsupervised AIDS pt. catches fire while smoking. Case on point: Lawson v.
      Skyline Healthcare Center, 2001 WL 1190581 P.2d-CA.

PMID- 11998260
TI  - Quality assurance and continuing education needs of rural and remote general
      practitioners: how are they changing?
AB  - The Royal Australian College of General Practitioners' (RACGP) 1998 Rural Quality
      Assurance and Continuing Education (QA & CE) Needs Assessment Project was
      designed to generate sufficient data to inform strategic planning for rural and
      remote GPs participating in the College's QA & CE Program. Results indicated that
      the demand for QA & CE activities has changed over the past 12 years. Three
      distinct streams of continuing education emerged, where once only one was
      researched. This reflected a move towards continuing professional development
      (CPD) rather than purely continuing medical education (CME). However, differences
      between the CME needs identified suggested that national data could not be
      reduced to the local level. Data on CME in which rural and remote GPs felt
      underserviced, proved more useful in relation to other workforce variables such
      as age, length of service and gender. A broad 'rural set' of CPD topics was
      established, and the survey yielded information on learning format preferences
      that will be of use to providers of QA & CE activities for rural GPs across
      Australia.

PMID- 11998261
TI  - Hospital separations indicate increasing need for prevention of diabetic foot
      complications in central Australia.
AB  - The aim of this study was to guide service provision for prevention of diabetic
      foot complications through the analysis of hospital separation data for those
      with diabetes in central Australia. We reviewed the hospital separation data for
      central Australia from 1992 to 1997 for adults known to be diabetic and those
      with diabetic foot complications. Foot complications were identified from
      International Classification of Diseases-9th Revision (ICD-9) codes.
      Additionally, we assessed the proportion of cases with diabetic foot, identified
      by ICD-9 coding and confirmed by record review, that were identified by
      Australian National-Diagnostic Related Group-Version 3 (AN-DRG-3) coding.
      Separations with diabetes doubled from 352 in 1992 to 796 in 1997. This
      represents an increase from 1232 to 2521 separations per 100,000 people over 15
      years of age. Separations with foot complications increased threefold from 28 in
      1992 to 90 in 1997, a rate increase from 98 to 285 per 100,000 people over 15
      years of age. The proportion of diabetes separations that had foot complications
      remained around 10% during the 6 year period. Aboriginal people made up 89% of
      the individuals with foot complications and 91% of separations for diabetic foot.
      Foot complications were predominantly of the more acute type (90%), amenable to
      early intervention. The AN-DRG-3 code for diabetic foot identified only 59%
      (37/63 in 1997) of the separations identified by the ICD-9 codes, and admitted
      primarily for foot complications in Alice Springs Hospital. The known burden of
      hospital care for diabetes and diabetic foot complications has increased markedly
      in recent years. A combination of changes in prevalence, primary care
      utilisation, detection, hospital access or re-admission rates may underlie the
      observed increases. As it is very unlikely that diabetes or diabetic foot
      complications are being over diagnosed, or that the hospitals are over utilised,
      this analysis shows there is an increasingly apparent need for improved
      prevention of diabetic foot complications. Therefore primary health care systems
      should ensure that they implement evidence-based care for preventing foot
      complications among people with diabetes.

PMID- 11998262
TI  - Risky business: stories from the field of rural community nurses' work in
      domestic violence.
AB  - This paper reports on a descriptive study into family violence in rural Victoria.
      Focus groups were held in a number of areas across rural Victoria with a total of
      24 community nurse participants. The focus groups were audio-taped and the tapes
      transcribed to enable the clustering of themes. The dominant themes were: picking
      up cues, helping and helplessness, holding secrets and quiet resistance.
      Underpinning all these themes however, was the notion of 'risky business'. All
      nurses in the study gave examples of situations that they encountered; their ways
      of helping; of working around a system that is unhelpful; and the ways in which
      their work while skilled, thoughtful and wise, is also costly in terms of the
      emotional wounds they carry. Rural nurses work with considerable risk and courage
      as they engage in the care and support of women experiencing family violence.

PMID- 11998263
TI  - Stretching district nursing services to meet rural needs.
AB  - This article evaluates the adequacy of District Nursing Service (DNS) provision
      in the Goulburn Murray region in Victoria. It draws on a survey of the region's
      DNS and communication with several community health agencies in response to
      problems identified by service providers. The results suggest that these rural
      health services face problems not experienced in urban areas. District nurses in
      rural areas have to travel far and wide to accommodate their clients and they put
      in extra unpaid hours if necessary. Their travel time, management and
      communication skills are not sufficiently recognised in the current funding
      formula. Although this includes some weighting for rurality, it is insufficient
      for District Nursing Services catering for smaller, more dispersed populations.
      Current and future demand pressures on home and community-based nursing services
      highlight the importance of redressing this deficiency. Several issues raised in
      this article may reflect problems that are common in rural regions, including
      funding inadequacies, unpaid additional work, access and equity difficulties and
      boundary issues. As a result, recommendations to improve service delivery may
      have broader applicability.

PMID- 11998264
TI  - Preventive social health programs: are they Australia's answer to rising health
      care costs in rural communities?
AB  - Although we have good evidence to support the notion that early intervention,
      prevention and community education programs can mitigate the impact of
      preventable disease, expanded primary health care is also being promoted by
      Australian governments as a panacea for reducing growth in demand generally.
      While preventive programs do reduce acute demand, they may not do so the extent
      that resources, currently allocated to the acute sector, can be substituted to
      provide the additional primary care services necessary to reduce acute demand
      permanently. These developments have particular relevance for rural and isolated
      communities where access to acute services is already very limited. What appears
      to be occurring, in rural South Australia at least, is that traditional acute
      services are being reduced and replaced with lower level care and social
      intervention programs. This is well and good, but eventually the acute care being
      provided in rural health units now will still need to be provided by other units
      elsewhere and probably at much higher cost to the system and to consumers. Where
      rural communities have previously managed much of their own acute service demand,
      they may now be forced to send patients to more distant centres for care but at
      much greater social and economic cost to individuals and the system.

PMID- 11998265
TI  - Work experience program at a metropolitan paediatric hospital: assisting rural
      and metropolitan allied health professionals exchange clinical skills.
AB  - The needs of rural allied health professionals (AHPs) have been widely
      documented. In particular, problems of professional isolation, lack of
      professional development opportunities and limited support systems have been
      highlighted as problems associated with working in rural and remote areas. This
      research aimed to provide rural and remote AHPs with an opportunity to gain
      experience in paediatric clinical areas of their choice, to provide rural/remote
      and metropolitan AHPs with an opportunity to share clinical knowledge and
      expertise, and to develop networks between rural/remote and metropolitan AHPs. A
      clinical experience program was developed to meet these aims. Twenty-nine AHPs
      from rural and remote areas of Queensland participated in the program.
      Participants completed questionnaires at the end of clinical experience program
      and 4-8 weeks after the visit. A focus group was also conducted. Analyses found
      the program met the majority of participants goals and expectations. Enhanced
      clinical skills in specialist paediatric areas, increased networking and access
      to resources were reported by rural/remote AHPs as benefits of the program. The
      role of a clinical consultant was found to be critical to the success of the
      program.

PMID- 11998266
TI  - Approach to sustainable primary health care service delivery for rural and remote
      South Australia.
AB  - We describe the operation of four University Teaching Practices established by
      the South Australian Centre for Rural and Remote Health (SACRRH) and the Adelaide
      University Department of General Practice. These practices were established in
      response to the acknowledged difficulty in recruiting and retaining GPs in rural
      South Australia. The practices are co-located with a hospital or accident and
      emergency service and community based nurses and allied health professionals.
      They provide integrated health care and multidisciplinary health care student
      placements in a learning environment where students experience rural
      multidisciplinary practice and country life. The study found that although the
      sites differed in significant ways, they all provided integrated care and
      effective placements for students. This style of health care delivery is flexible
      and broadly applicable. Sustainability is achieved through financially viability,
      attracting and retaining health care professionals and the development of
      electronic information systems, to support integrated practice.

PMID- 11998267
TI  - Use of Medicare services related to diabetes care: the impact of rural isolation.
AB  - This study used Medicare data for people living in New South Wales (NSW) (1993
      1997) to examine the impact of rural isolation on the utilisation of diabetes
      health care services. The relative odds of attending a specialist was slightly
      higher for people in urban areas when compared to their rural counterparts but
      reached as high as 1.85 in regard to attendance to consultant physicians.
      Surveillance of diabetes parameters over the 5 year period showed greatest
      improvement in rural areas. The proportion of patients each year with glycaemic
      control assessed by quantification of glycosylated haemoglobin (HbA1c) or renal
      function and vascular risk by microalbuminuria estimation rose to 57.4% and
      12.3%, respectively, in rural areas compared to 55.2% and 11.3% in major urban
      areas. This study has shown that the level of monitoring in rural areas is equal
      to urban areas, despite decreased access to medical care, highlighting the vital
      role GPs play in diabetes management in rural NSW.

PMID- 11998268
TI  - Rural decline.

PMID- 11998269
TI  - Vertical integration and its role in workforce education and support: ACRRM's
      academic role.

PMID- 11998270
TI  - Community based medical education in a rural area: a new direction in
      undergraduate training.
AB  - The Greater Murray Clinical School provides a community based medical education
      programme for the clinical years at the University of New South Wales. Being a
      new clinica school in rural Australia allowed the development of a patient
      centred longitudinal curriculum. Students follow patients through the health care
      system, with each exposure stimulating the learning about different aspects of a
      patient problem. The paper outlines the conceptual approach towards the
      development and implementation of this novel approach to community based medical
      education.

PMID- 11998271
TI  - Rural interprofessional education: promoting teamwork in primary health care
      education and practice.
AB  - In a climate of increasing incentives to work effectively within a primary health
      care team, the ability of various health care professionals to collaborate comes
      into focus. The principles of effective teamwork can be learned and this learning
      is most effectively achieved in the field under the supervision of experienced
      preceptors. It is also enhanced if learners have the opportunity to participate
      actively in the team and do so from undergraduate level. A 3 year project is
      underway in Victoria involving rural primary care placements for mixed groups of
      nursing and medical students. The students are educated in the field by medical
      and nursing tutors and preceptors who are currently working closely together. The
      learning objectives include understanding the principles of collaboration,
      teamwork and various roles in the health care team within a primary health care
      framework. The present paper describes the context for an evolving
      interprofessional education project in rural primary care, designed to promote
      collaboration. It outlines the policy underpinning the project's development. It
      provides a brief review of the associated evidence base, highlighting barriers to
      and enablers of interprofessional education. Lessons learnt during the
      implementation and evaluation of this project will guide efforts to extend the
      reach of interprofessional education across the primary health care sector.

PMID- 11998272
TI  - Rural initiatives at the James Cook University School of Medicine: a vertically
      integrated regional/rural/remote medical education provider.
AB  - Building on the success of the former North Queensland Clinical School/Royal
      Australian College of General Practitioners collaboration in North Queensland,
      the James Cook University School of Medicine continues to develop a model of
      close collaboration with stakeholder groups that provides medical education
      services to dispersed communities in northern Australia. The flagship themes of
      the programme (rural & remote, Indigenous and tropical health) are essential to
      the regional mission to improve the health care of people in northern Australia.
      Selection processes target regional and rural background students and Aboriginal
      and Torres Strait Islander students. An innovative curriculum design reinforces
      interest in and relevance to regional health needs. The present paper provides an
      overview of the roles and early progress of the new School of Medicine, with the
      aim of keeping rural doctors informed about the continuing development of a
      successful 'national standards/local collaboration and control' model of
      education service delivery.

PMID- 11998273
TI  - Rural rotations for interns: a demonstration programme in South Australia.
AB  - The Commonwealth Government of Australia, through policy initiatives and
      increased funding, has placed significant emphasis on increasing undergraduate
      rural experiences for medical students. However, in the immediate postgraduate
      years, rural community based rotations are uncommon, with the vast majority of
      intern experiences remaining hospital based. Since 1997, Flinders Medical Centre,
      Flinders University and the rural communities of Cleve and Jamestown have run a
      preregistration rural intern-training position based in rural general practice.
      The present article describes the programme, its evolution and the problems that
      have been overcome. The term provides a blend of hospital and community based
      experiences appropriate for junior doctors not yet familiar with ambulatory care.
      At the same time, the junior doctors have consistently reported a high-quality
      learning experience, with ready access to patients and procedural work. We
      describe the qualitative and quantitative methods we have recently introduced for
      evaluation of the programme.

PMID- 11998274
TI  - Regionalisation of rural medical training in far north Queensland: a learning
      experience for medical educators and managers.
AB  - The need for an appropriate, dedicated vertically-integrated training pathway for
      rural doctors, provided by regional consortia of educational organisations, has
      been clearly identified by Rural Doctors Association of Queensland (RDAQ) and The
      Australian College of Rural and Remote Medicine (ACRRM) as a key strategy to
      resolve rural medical workforce issues. The opportunity to put the ideas into
      action is now here with rural doctors responding to the challenge of managing
      more reform in general practice all over Australia. In Far North Queensland, the
      ongoing reform of general practice education has been challenging, with many
      lessons learned by both educators and managers. This paper describes the
      management of change, and outlines key principles and characteristics of a
      successful regional rural medical training system, building on the lessons
      learned from the Rural and Remote Area Placement Program (RRAP) and other
      projects.

PMID- 11998275
TI  - Outcomes in rural obstetrics, Atherton Hospital 1991-2000.
AB  - Analysis of annual obstetric audit data collected over the decade 1991-2000 from
      the Atherton Hospital in Far North Queensland provides ongoing evidence of safe
      obstetric practice provided by a group of non-specialist doctors in a rural
      community. During that period, there were 2997 deliveries; of these, 2400 (80.1%)
      were public patients and 596 (19.9%) were private patients. There were 16
      perinatal deaths (perinatal mortality rate 5.3/1000). This is remarkably
      consistent with the outcome of the previous decade, 1981-90, when the total
      deliveries was 2883 with 15 perinatal deaths (perinatal mortality rate 5.2/1000).
      However, compared with 1981-90, the number of Caesarean sections rose from an
      overall rate of 13.0% (public 10.6%; private 18.3%) to an overall rate of 17.4%
      (public 16.7%; private 20.4%). In 1981-90, there were 909 private confinements
      (31.5% of total) and in 1991-2000 there were 597 (19.9% of total). This decline
      in the number of private obstetric cases may have significant implications for
      future models of care. There were no maternal deaths in the 20 years 1981-2000.

PMID- 11998276
TI  - Sustainable rural practice for female general practitioners.
AB  - An expert panel of female rural and remote doctors have nominated updating
      professional skills as the most important strategy for sustainable rural general
      practice for women. The panel was comprised of members of the Australian College
      of Rural and Remote Medicine (ACRRM). The panel was asked to identify and
      prioritise strategies they had used to make rural practice work for them. They
      identified and ranked the following eight groups of strategies: (i) structure
      medical practice to work for you; (ii) implement personal strategies; (iii)
      obtain and update professional skills; (iv) establish professional and personal
      boundaries; (v) gain exposure to rural practice; (vi) engage with the community;
      (vii) implement professional strategies; and (viii) engage with women. Detailed
      strategies within these groups have been identified and will form the basis of
      grounded knowledge about how to structure rural and remote practice to work for
      women. This will complement the work of ACRRM, the Rural Doctors Association and
      workforce agencies in developing models of sustainable rural medical practice.

PMID- 11998277
TI  - Use of a clinical audit to promote the quality use of medicines to rural and
      remote general practitioners.
AB  - Very few methods have been shown to change prescribing behaviour. Queensland
      Rural Medical Support Agency's Quality Use of Medicines (QUM) Program aims to
      engage rural general practitioners (GPs) in the development of strategies to
      improve health outcomes in relation to the quality use of medicines. The present
      paper describes the development of a tool to audit the management of heart
      failure in rural general practice and to encourage rural GPs to undertake such an
      audit as a method of continuing medical education. A self-administered
      retrospective clinical audit of heart failure patients was undertaken by rural
      and remote GPs. Fourteen doctors undertook the audit, providing data on 270
      patient cases. Patient data collected include 30% not receiving adequate
      angiotensin-converting enzyme inhibitor doses, 45% of patients who may benefit
      from a beta-blocker and 14% of patients taking a drug known to aggravate heart
      failure. The majority of participants would review a patient following the audit
      and 93% confirmed that the audit assisted them in identifying patients whose
      heart failure management could be enhanced. The clinical audit provided results
      and a commentary to allow GPs reflective educational opportunities through the
      dissemination of results and engagement with appropriate educational
      organisations (e.g. Australian College of Rural and Remote Medicine) to inform
      the development of educational standards for personal development programs in
      QUM. Audits must be relevant and practical to meet the learning needs of GPs.

PMID- 11998278
TI  - Rural career choice issues as reported by first year medical students and rural
      general practitioners.
AB  - Governments have recently instituted several programmes designed to attract
      medical students to rural practice. Questions may be raised as to whether
      interventions based around issues identified as important to practising rural
      general practitioners (GPs) are equally applicable to undergraduate medical
      students. The results of two studies on the importance of personal and practice
      issues as ascribed by Australian rural GPs and Victorian medical students are
      analysed. The effect of the students' gender, place of origin and intended
      location of practice is assessed. Findings suggest that practising GPs may have
      resolved many of the student issues and may be well placed to advise students on
      perceived hurdles to rural practice. Furthermore, students may be seeking a
      practice style similar to that sought by female GPs. The present paper concludes
      that while there are similarities between the groups, the differences identified
      support caution when basing student programmes on research performed on rural
      GPs.

PMID- 11998279
TI  - Urinary incontinence after radical prostatectomy: implications and urodynamics.
AB  - OBJECTIVES: The purpose of this study was to evaluate urine loss, quality of
      life, and urodynamics in men who had urinary incontinence after radical
      prostatectomy and who were at least 12 months post surgery. SUBJECTS AND METHODS:
      Men from a previous study (N = 180) regarding quality of life and treatment of
      incontinence post prostatectomy were solicited. Twenty-one men were still
      incontinent 2 or more years post surgery; 16 agreed to further evaluation. The
      latter patients completed a 24-hour pad test, frequency/volume chart, quality-of
      life questionnaire, and underwent video urodynamics. RESULTS: Median time from
      surgery was 22 months (14 to 33 months) and the mean urine loss over 24 hours was
      164 g. Incontinence had an impact on quality of life, but men adjusted their
      lives and most would undergo radical prostatectomy again. Half of the subjects
      experiencing stress urinary incontinence on urodynamics also had a component of
      detrusor dysfunction (urge incontinence/decreased compliance). CONCLUSIONS:
      Quality of life was significantly affected by urinary incontinence, but most
      subjects would undergo radical prostatectomy again. Symptoms of stress urinary
      incontinence alone may not reflect the urodynamic diagnosis. Detrusor dysfunction
      should be considered in the etiology of incontinence after radical prostatectomy.

PMID- 11998280
TI  - Urinary incontinence in vulnerable populations: female soldiers.
AB  - Stress urinary incontinence (SUI) is prevalent in women of all ages. Due to the
      rigorous demands of military life, physical fitness requirements, and
      environmental barriers, female soldiers are at risk for SUI. Since it is
      estimated that 20% of the total U.S. military active-duty force in the future
      will be women, it is important to focus on this problem now.

PMID- 11998282
TI  - Getting ready for certification: urodynamic testing in assessing voiding
      dysfunction.

PMID- 11998283
TI  - AFUD publicizes risks of cigarette smoking.

PMID- 11998284
TI  - Legislation aims to prevent deadly needlestick injuries.

PMID- 11998285
TI  - Quality of life returns to normal in year following brachytherapy.

PMID- 11998286
TI  - Female stress urinary incontinence facts.

PMID- 11998287
TI  - A matter of life or death.

PMID- 11998288
TI  - Management of primary nocturnal enuresis.
AB  - Most parents believe that their child should not be wetting the bed by age 5.
      Statistics show that 10% to 20% of 5 year olds continue with a least one episode
      of nocturnal enuresis per month. There is evidence that successful treatment
      leads to improved self-concept in children (Moffatt, Kato, & Pless, 1987).
      Treatment consists of various behavior modifications or pharmacologic regimes.
      Nurses and nurse practitioners in family practice, pediatric practice, school
      health, and urologic practice are in ideal roles to seek out and manage children
      with primary nocturnal enuresis.

PMID- 11998289
TI  - Assessment and intervention knowledge of nurses in managing catheter patency in
      continuous bladder irrigation following TURP.
AB  - Continuous bladder irrigation (CBI) is an established procedure designed to
      prevent the formation and retention of blood clots following transurethral
      prostatectomy (TURP). The purpose of this study was to evaluate a tool designed
      to determine what steps the nurse should follow to assess whether a catheter is
      blocked and the actions to be taken to restore catheter patency for CBI.

PMID- 11998290
TI  - School of nursing teams with regional health-care organizations to attack
      Nebraska's nursing shortage.

PMID- 11998292
TI  - Is a common health care language coming our way?

PMID- 11998293
TI  - Your answers to issues in the workplace.

PMID- 11998294
TI  - A mini journey into transcultural nursing with its founder.

PMID- 11998295
TI  - Violence in the workplace: nurses at risk.

PMID- 11998296
TI  - Understanding organ and tissue donation.

PMID- 11998297
TI  - What can we do?

PMID- 11998298
TI  - A call to action for nurses: declining enrollment and the nursing shortage.
AB  - Once again, nursing and health care face a crisis related to the continued
      decline in nursing school enrollment and the nursing shortage. This particular
      shortage seems to be especially problematic because of the increased number of
      aging baby boomers and the dwindling professional nurse pool. Nurses must work
      together to increase understanding and awareness of the opportunities in the
      profession and to resolve this crisis. There are specific actions nurses can take
      to improve the perception of nursing and renew interest in a dynamic field that
      is so crucial to society.

PMID- 11998299
TI  - Urinary diversions: a review of nursing care.
AB  - The nurse plays an important part in the preoperative and postoperative
      management of the patient with a urinary diversion. Although urinary diversion as
      a surgical alternative has been performed since the mid 1800s, improvements in
      technique and management over the past 10 years warrant discussion. Three types
      of urinary diversion procedures are discussed along with suggestions for optimal
      nursing management during the postoperative period.

PMID- 11998300
TI  - A comparison of two enuresis alarms.
AB  - This randomized experiment was undertaken to determine if any difference in
      success occurred between an audio versus a vibration alarm for nocturnal
      enuresis. Similar rates of success were achieved for 47 children, aged 6 to 12
      years, who partially or totally completed the 3-month period of alarm use.

PMID- 11998301
TI  - Similar symptoms and confounding conditions: benign prostatic hyperplasia versus
      hyperglycemia.
AB  - The traditional approach to diagnosing men with symptoms associated with benign
      prostatic hyperplasia (BPH) based on the American Urological Association symptom
      index may be limiting. There are often concurrent conditions that may be
      responsible for the urinary complaints of men with BPH, namely hyperglycemia.
      Both conditions manifest many of the same symptoms and complaints by patients,
      but treatment of one can lead to a missed diagnosis of the other.

PMID- 11998302
TI  - Utilization of a self-administered questionnaire to assess rectal function
      following prostate brachytherapy.
AB  - A sample of 209 consecutive prostate brachytherapy patients completed a self
      administered questionnaire to evaluate bowel changes following treatment. With a
      median followup of 28 months, less than 20% of patients reported deterioration in
      bowel function.

PMID- 11998303
TI  - NIH to study common prostate condition.

PMID- 11998304
TI  - Successful vasectomy reversals becoming more common with new surgical techniques.

PMID- 11998305
TI  - Stem cells used to treat incontinence in animal models.

PMID- 11998307
TI  - Views on bladder scan.

PMID- 11998308
TI  - Proposed resolution. Kansas nursing shortage action plan development.

PMID- 11998309
TI  - Compulsive gambling: a women's health risk.

PMID- 11998310
TI  - Alcohol, tobacco, and other drugs can be harmful to pregnant women and their
      infants.

PMID- 11998311
TI  - Coping with caregiver strain: when the patient is your parent.

PMID- 11998312
TI  - First paralytic shellfish poison (PSP) infestation of bivalves due to toxic
      dinoflagellate Alexandrium tamiyavanichii, in the southeast coasts of the Seto
      Inland Sea, Japan.
AB  - The mussel Mytilus edulis and the cultured ark shell Anadara broughtonii in the
      southeast coasts of the Seto Inland Sea were contaminated with paralytic
      shellfish poison (PSP) following the appearance of the dinoflagellate Alexandrium
      tamiyavanichii in early December 1999. A. tamiyavanichii plankton collected
      around the Straits of Naruto on December 3, 1999 showed PSP toxicity, of which 83
      mol% was accounted for by GTX2, GTX3 and GTX4. Its specific toxicity was 112.5
      fmol/cell, and one MU was equivalent to 7,200 cells. Toxicity values at the
      beginning of toxification were 4.7 MU/g for the ark shell and 7.3 MU/g for the
      mussel. In the former, the value remained at almost 4 MU/g, resulting in
      prohibition of marketing for about two months. In the latter, it sharply
      decreased to less than 4 MU/g. These bivalves collected during the toxification
      period were dissected into five tissues, mantle, adductor muscle, hepatopancreas,
      gills and "others", and submitted to high-performance liquid chromatography
      (HPLC). The cultured ark shell accumulated GTX2, GTX3 and STX as major components
      and GTX1, GTX4, GTX5, neoSTX, dcSTX and PX1-3 (C1-C3) as minor ones. The amount
      of GTX3 decreased with time, while STX tended to increase. At the early stage of
      PSP toxification, toxins were accumulated in the gills and "others", most of
      which were quickly detoxified. On the other hand, PSP of the toxified mussel
      consisted of GTX4 as a main component, and GTX1, GTX2, GTX3, GTX5, STX and PX1-2
      (C1-C2) as minor ones. Its toxin composition pattern was similar to that of the
      ingested causative plankton. Its total toxin decreased soon after disappearance
      of the dinoflagellate. During the decrease of toxicity, PSP tended to be retained
      in the hepatopancreas, resulting in accumulation of 50 mol% of total toxin.

PMID- 11998313
TI  - [Determination of isothiocyanates and related compounds in mustard extract and
      horseradish extract used as natural food additives].
AB  - Amounts of isothiocyanates and related compounds in a mustard extract and a
      horseradish extract for food additive use were determined by GC, after
      confirmation of the identity of GC peaks by GC/MS. Amounts of allyl
      isothiocyanate, which included that of allyl thiocyanate, because most of the
      allyl thiocyanate detected in the sample was assumed to have been formed from
      allyl isothiocyanate during GC analysis, were 97.6% and 85.4%, in the mustard
      extract and the horseradish extract, respectively. Total amounts of the
      identified isothiocyanates in the mustard extract and the horseradish extract
      were 98.5% and 95.4%, respectively. Allyl cyanide, a degradation product of allyl
      isothiocyanate, was found in the mustard extract and the horseradish extract at
      the levels of 0.57% and 1.73%, respectively. beta-Phenylethyl cyanide, a possible
      degradation product of beta-phenylethyl isothiocyanate, and allyl sulfides were
      found in the horseradish extract, at the levels of 0.13% and 0.46%, respectively.
      Allylamine, which is another degradation product of allyl isothiocyanate, was
      determined after acetylation, and was found in the mustard extract and the
      horseradish extract at the levels of 8 micrograms/g and 67 micrograms/g,
      respectively.

PMID- 11998314
TI  - Structure of acid-stable carmine.
AB  - Acid-stable carmine has recently been distributed in the U.S. market because of
      its good acid stability, but it is not permitted in Japan. We analyzed and
      determined the structure of the major pigment in acid-stable carmine, in order to
      establish an analytical method for it. Carminic acid was transformed into a
      different type of pigment, named acid-stable carmine, through amination when
      heated in ammonia solution. The features of the structure were clarified using a
      model compound, purpurin, in which the orientation of hydroxyl groups on the A
      ring of the anthraquinone skeleton is the same as that of carminic acid. By
      spectroscopic means and the synthesis of acid-stable carmine and purpurin
      derivatives, the structure of the major pigment in acid-stable carmine was
      established as 4-aminocarminic acid, a novel compound.

PMID- 11998315
TI  - [A detection method of recombinant DNA from genetically modified potato (NewLeaf
      Plus potato) and detection of NewLeaf Plus potato in snack].
AB  - A detection method using polymerase chain reaction (PCR) was developed to detect
      the genetically modified (GM) potato (NewLeaf Plus potato; NL-P), which has not
      been authorized as safe in foods in Japan. The potato sucrose synthase gene was
      used as an internal control. The DNA from NL-P specifically provided an amplified
      band using PCR with a primer pair recognizing PLRV-rep gene. In addition, to
      prevent false-positive results in processed potato foods infected with PLRV, we
      designed a primer pair recognizing sequences derived from two organisms to detect
      specifically NL-P in processed potato. The PCR product obtained using the
      designed primer pair was specific for NL-P. The DNA introduced into NL-P could be
      detected from potato powder samples containing 0.05% NL-P. The proposed method
      was applied to the detection of NL-P in 25 processed potato foods. NL-P was
      detected in 3 snack products.

PMID- 11998316
TI  - [Determination of ethychlozate and its degradation product in fruits by HPLC and
      LC/MS].
AB  - A method was developed for the analysis of ethychlozate (CIE) and its
      decomposition compound, 5-chloro-3(1H)-indazolylacetic acid (CIA) in fruits by
      HPLC and LC/MS. The sample was homogenized with 1 mol/L HC1, and CIE and CIA were
      extracted with 5 mol/L HCl and acetone. They were extracted from the acetone
      extract with diethylether-n-hexane (2:1). CIE was hydrolyzed to CIA with methanol
      4 mol/L KOH (1:1). The solution was made acidic, and CIA was extracted with
      diethylether-n-hexane (2:1). The extract was cleaned up on a silica gel column.
      CIA was determined by HPLC-UV and LC/MS (Scan or SIR). Four fruits were spiked
      with CIE or CIA at 0.5 microgram/g and analyzed by the proposed method with HPLC.
      The average recoveries were 77.2-83.2% for CIE and 71.2-89.2% for CIA. The
      concentrations determined by LC/MS were 10-25% higher than the values by HPLC.
      The limit of detection (LOD) of CIA standard solution by HPLC corresponds to
      0.015 microgram/g of CIE in the sample. In the same way, the LOD of CIA by LC/MS
      (SIR) corresponds to 0.009 microgram/g of CIE in the sample.

PMID- 11998317
TI  - [Determination of dimethylformamide in food additive sucrose esters of fatty
      acids using solid-phase extraction].
AB  - A simple method using Florisil cartridges was developed for the determination of
      dimethylformamide (DMF) in sucrose esters of fatty acids present in sugar esters
      (SuE) and sucrose acetate isobutyrate (SAIB) used as food additives. SuE was
      dissolved in acetone and loaded on a Florisil cartridge. SAIB was dissolved in
      hexane, loaded on a Florisil cartridge and washed with 10% acetone in hexane. The
      columns were eluted with acetone and DMF in the eluates was determined by GC with
      an FID detector. Recoveries of DMF at the level of 0.5-100 micrograms/g were 93.3
      102.6%. The determination limit was 0.5 microgram/g.

PMID- 11998318
TI  - [Determination of K-value and histamine of mackerel and tuna, by using the oxygen
      sensor method].
AB  - Determination of K-value (fish freshness index) and histamine (Hm) of mackerel
      and tuna during storage at various temperatures was done by using the oxygen
      sensor method. Hm in mackerel increased even at low temperature (5 degrees C),
      and reached the Defect Action Level (DAL) of the U.S. FDA, 5 mg/100 g, before the
      K-value approached the inedible level. As the storage temperature was increased,
      the rate of Hm formation increased remarkably and the amount of Hm in fish meat
      passed through the DAL, and reached the real hazard level, AL (50 mg/100 g), in a
      short time. The initial Hm level of raw tuna was too low to determine by our
      oxygen-sensor method, and the final Hm level after 8 days' storage at under 5
      degrees C was only 0.6 mg/100 g. But, when the storage temperature was elevated,
      the rate of Hm formation increased rapidly, as in mackerel, and the Hm level
      reached the DAL, then the AL, in a short time. Simultaneous determination of K
      value and Hm is recommended for accurate and reliable quality inspection of fish
      and fish products.

PMID- 11998319
TI  - [Spore rec-assay by dry sheet medium culture plate for bacterial counts].
AB  - A simple and rapid method for spore rec-assay by utilizing dry sheet medium
      culture (Compactdry TC, CTC) for determining numbers of bacteria, instead of the
      spore agar plate, was developed. One mL of spore suspension (2 x 10(6)/mL) of
      Bacillus subtilis strain M45 Rec- or H17 Rec+ was inoculated in the center of the
      CTC plate. In the case of metabolic activation, 1 mL of mixed solution (spore
      suspension of M45 or H17: 9,000 x g supernatant of rat-liver homogenate treated
      with Aroclor 1254 = 19:1) was used. The spore suspension spreads over the whole
      sheet in seconds and gels. A paper disk impregnated with 20-40 microL of the
      sample solution and 20 microL of the cofactor solution was placed on the surface
      of CTC plate. For the assay of samples that do not require metabolic activation,
      use of the cofactor solution can be omitted. After 48 hr incubation at 37 degrees
      C, 0.01% MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]
      aqueous solution (0.5 mL) was dropped uniformly on the plate. The plate was left
      for 5 min, and the diameter of the inhibition circle was measured with slide
      calipers. The samples for which the difference in inhibition zone between M45 and
      H17 was more than 2 mm were judged positive. Under these conditions, the DNA
      damaging activities of sodium sulfite, sodium benzoate and citric acid, used as
      food additives, were investigated by the proposed method. Sodium sulfite and
      sodium benzoate gave positive results and citric acid gave a negative result with
      or without metabolic activation, in agreement with the results obtained by the
      conventional method.

PMID- 11998320
TI  - Estimation of concentrations of antifungal agents allowed as food additives in
      foods and their daily intake based on official inspection results in Japan in
      fiscal year 1998.
AB  - The mean concentrations and daily intake of four antifungal agents were estimated
      based on the results of an analysis of 7,005 samples of food obtained in official
      inspections by Japanese local governments in fiscal year 1998. The mean
      concentration of diphenyl was 0.0004% of the allowable limit, and those of
      imazalil, o-phenylphenol, and thiabendazole were 14.0%, 3.5%, and 5.7%,
      respectively. The daily intakes of these antifungal agents per person, estimated
      from their concentrations and the daily consumption of the foods, were 0.000326,
      1.89, 11.5, and 23.3 micrograms, respectively, and assuming a body weight of 50
      kg, the amounts of these antifungal agents consumed were 0.000013%, 0.15%, 0.12%,
      and 0.47% of the acceptable daily intake, respectively. These values are similar
      to the values obtained on the basis of the results of the official inspection in
      fiscal years 1994 and 1996, except that the amount of diphenyl is much lower
      (1/100).

PMID- 11998321
TI  - [Determination of levamisole in livestock products using high performance liquid
      chromatography].
AB  - A method is described for the determination of the anthelmintic levamisole in
      muscle, liver, kidney and fat of cattle, swine and poultry using high performance
      liquid chromatography with photodiode array detection. Levamisole was extracted
      from an alkaline sample with ethyl acetate and back-extracted with 0.1 mol/L
      hydrochloric acid. The extract was applied to an SCX solid-phase extraction
      column. The column was washed with water and methanol. Levamisole was eluted with
      a solution of ammonia in methanol. The eluate was evaporated to dryness and the
      residue was dissolved in the mobile phase and injected into the HPLC system. Mean
      recoveries from 0.01-0.10 microgram/g fortified muscle, liver, kidney and fat
      samples ranged from 78.3 to 99.8%. The detection limit for the assay was 0.005
      microgram/g.

PMID- 11998322
TI  - [Thickening stabilizer from seaweeds].

PMID- 11998323
TI  - [Nitrate in vegetables].

PMID- 11998324
TI  - [Good laboratory practice (GLP) and ISO9002 Registration of Quality Management
      System in the field of food hygiene].

PMID- 11998325
TI  - [Basic knowledge of compost].

PMID- 11998326
TI  - [Science, the Expert, the Physician and the Octogenarian].

PMID- 11998327
TI  - [Myocardial revascularization at the acute phase of myocardial infarction in the
      octogenarian].
AB  - Elderly patients are at high risk of complications in acute myocardial infarction
      (AMI). In this population, myocardial reperfusion at the acute phase improves the
      prognostic. The mortality rate is above 50% in the absence of reperfusion
      strategy, and decreases at less than 20% in case of such treatment. The
      thrombolytic use is limited in those patients, coronary angioplasty is taking an
      important place in this reperfusion therapy, but is not well evaluated in
      patients older than 80 years. Prospective registry of patients older than 80
      years admitted in Hopital Bichat for acute myocardial infarction within the first
      6 hours (n = 92), between 1990 january to 1999 december. Eight patients (10%)
      received a thrombolytic therapy. Coronary angiogram was achieved in eighty
      patients (87%). In 58 (63%) patients a coronary angioplasty was performed. The
      success rate of the coronary angioplasty was 86%. In-hospital mortality rate was
      26% (death in 24 patients), 20% in the absence of cardiogenic shock and 62% when
      this complication was noted. Two patients (2%) were treated by emergent coronary
      artery bypass surgery. The results comparison between the periods of 1990 to 95
      and 1955 to 99 showed, a real trend of decrease mortality rate (28 to 13% in the
      absence of cardiogenic shock, p = 0.10), an increase of the proportion of
      patients treated by angioplasty. These results are more and more encouraging.
      Coronary reperfusion by primary angioplasty in possible in patients older than 80
      years with a low rate of complications. Technical progress such as stents and
      GpIIb/IIIa inhibitors must be evaluated in this population.

PMID- 11998328
TI  - [Secondary prevention of myocardial infarction in the Ile de France].
AB  - This enquiry was carried out to evaluate the measures of secondary prevention at
      6 months and over of myocardial infarction in the ile de France region with
      respect to the recommendations of scientific societies and results of large scale
      therapeutic trials. A questionnaire was completed for the 1,215 patients selected
      from data obtained from the hospital discharge summary, interrogation and
      examination of the patient, and a telephone conversation with the attending
      physician. The data covered cardiovascular risk factors, the main clinical
      parameters, the results of biological tests and investigations carried out for
      risk stratification, plus different elements of therapeutic management. Compared
      with previous studies of the same type, this enquiry showed a favourable tendency
      towards the prescription of antithrombotic drugs and betablockers (98.3% and
      82.4% of patients, respectively), and to patients with reputedly normal blood
      pressure values (84.7%). A positive result concerning the reduction in the number
      of smokers (17.4%) and the increase in lipid lowering prescriptions should be
      tempered by the fact that advice about stopping smoking was rarely given and that
      the quantitative target of LDL cholesterol was often ignored. Finally, the
      prescriptions of ACE inhibitors, physical exercise and cardiac rehabilitation
      remained well below the recommendations or recent scientific data.

PMID- 11998329
TI  - [Multiple ruptures of atherosclerotic plaques in acute coronary syndrome.
      Endocoronary ultrasonography study of three arteries].
AB  - The aim of this study was to assess the three coronary arteries systematically by
      endocoronary ultrasonography in patients with unstable angina to check the
      hypothesis of global destabilisation of atherosclerotic plaques in acute coronary
      syndromes (ACS). Sixty two coronary arteries were examined (2.6 per patient).
      Fifty plaque ruptures were diagnosed (2.08 per patient). Rupture of a plaque of
      the culprit lesion of the ACS was clearly detected in 9 patients (37.5%). At
      least one ruptured plaque on a site other than the culprit lesion was observed in
      19 patients (79%), on another artery in 70.8% of cases and on two other arteries
      in 12.5% of cases. A complete endocoronary ultrasonic examination of the three
      coronary arteries in patients with a first ACS demonstrated that: multiple
      atherosclerotic plaque rupture may be detected by endocoronary ultrasonography;
      these multiple plaque ruptures occur simultaneously with the culprit lesion; they
      are frequent and can be situated on the three main coronary vessels and multiple
      plaque rupture other than the culprit lesion are less severe, non stenotic and
      less calcified. Thus, although a single lesion is clinically symptomatic, ACS
      seems to be associated with global coronary instability.

PMID- 11998330
TI  - [Four years followup of complicated Cockett syndrome treated by iliac vein
      endoprosthesis].
AB  - The purpose of this study was to check the long-term patency of the left common
      iliac vein endoprosthesis in Cockett syndrome and to confirm this appropriate
      etiological treatment in complicated cases. Three patients had respectively a
      pulmonary embolism, left common iliac vein occlusion with protein S deficiency,
      and venous claudication (Paget-von Schroetter syndrome) as complications of the
      Cockett syndrome. Treatment with endoprosthesis was performed. A mean follow-up
      of 48.6 months (31-61 months) revealed a clinical improvement without any
      recurrence of complications. The patency of the left common iliac vein flow was
      maintained. Indications on this treatment are being discussed.

PMID- 11998331
TI  - [Platelet polymorphism and coronary artery disease].
AB  - Several publications over the last ten years have addressed the problem of
      genetic mutation coding platelet membrane glycoproteins and thrombotic arterial
      disease. The principal polymorphisms studied are those of glycoproteins GPIIIa,
      GPIb and the GPIa-IIa complex. The relationships of each of these polymorphisms
      and myocardial infarction or coronary artery disease are reported and are often
      subject to controversy. The polymorphism PLA2 of the GPIIIa has been shown to be
      a risk factor for infarction in young people, especially when associated with
      cigarette smoking. Its role in triggering myocardial infarction or in the
      severity of coronary artery disease is not so clear in the general population.
      Two types of polymorphism concerning the GPIb and that of the GPIa-IIa complex
      should also predispose to early coronary thrombotic complications. In addition,
      the study of these platelet polymorphisms gives a better insight into individual
      sensitivity to platelet antiaggregant therapy.

PMID- 11998332
TI  - [Bradykinin and ventricular function].
AB  - Kinins are vasodilator peptides implicated in many physiological and
      physiopathological processes such as blood pressure regulation and that of the
      coronary circulation and inflammatory reactions. Kinins play an essential role in
      ventricular function as they counteract the effects of angiotensin II during
      myocardial ischaemia, ventricular remodelling and severe cardiac failure,
      emphasising the value of treatment favouring local endogenic production of
      bradykinin such as ACE inhibitors, neutral endopeptidase inhibitors and
      antagonists of AT1 receptors of angiotensin II.

PMID- 11998333
TI  - [Ultra-rapid measurement of brain natriuretic peptide].
AB  - B-type natriuretic peptide (BNP) is secreted by overloaded ventricles. Emerging
      of bedside dosages cause an increasing interest for this peptide as marker in
      various clinical situations with heart failure. At first, BNP dosage is a
      potential tool for detecting heart failure and left ventricular dysfunction. BNP
      has also a powerful and well-established prognosis value in chronic heart
      failure. In the emergency setting, and mainly about acute dyspnea, low blood BNP
      level could eliminate diagnosis of congestive heart failure. Moreover, serial
      measurement of BNP could allow non-invasive hemodynamic monitoring during
      decompensated heart failure and could also lead cares as need for intensifying
      treatment. Nevertheless, its daily use in various clinical situations require
      that cut-off values are refined.

PMID- 11998334
TI  - Angiogenesis therapy in ischemic disease.
AB  - The ability of organisms to spontaneously develop collateral vessels represents
      an important response to vascular occlusive diseases that determines the severity
      of residual tissue ischemia. Neovascularization of ischemic cardiac or skeletal
      muscle may be sufficient to preserve tissue integrity and/or function, and may
      thus be considered to be therapeutic. Innovative gene technologies and advances
      in animal modeling have enabled research scientists to develop therapeutic
      angiogenesis strategies applied in animal models of limb or myocardial ischemia
      and in treatment of patients with peripheral vascular obstruction or coronary
      artery diseases. Several therapeutic strategies have been proposed and tested
      even at the clinical level. Recent studies have established the feasibility of
      using recombinant angiogenic growth factors (mainly VEGF and FGF) to enhance
      angiogenesis in patients with limb or myocardial ischemia. Angiogenesis therapies
      using cells as a support for growth factor delivery or using endothelial
      progenitor cells which may directly participate in the angiogenic process have
      also been developed. Finally, one potential alternative strategy may be the use
      of drugs with pro-angiogenic activity, available in an oral formulation and which
      are currently administered to patients for treatment of different pathologies.
      All strategies of angiogenesis therapy currently being tested have the potential
      to be effective in the treatment of ischemic disease. However, such strategies
      may cause harmful side effects which emphasize the need to be aware of the
      biological effects of each angiogenic agent proposed for clinical studies.

PMID- 11998335
TI  - Myocardial gene therapy.
AB  - Myocardial gene therapy was born at the beginning of the 90's from the marriage
      of well-defined pathophysiological mechanisms with recombinant adenovirus
      technology. Together with the development of relatively simple vector delivery
      procedures during the last few years, this made it possible to consider the
      possibility of treating diseases such as ischemic cardiomyopathies by the
      delivery of angiogenic factors and to bring the first proof, in rats, that
      myocardial gene therapy for experimental heart failure can improve cardiac
      performance and prolong life duration of the animals. It is now conceivable that
      such an approach will be applied to human heart failure within the next years. In
      contrast, regarding familial cardiomyopathies and channelopathies, because of the
      specificity of each disease type and complexity of the pathophysiology of each
      mutation, it is likely that much more time will be necessary. However, a number
      of barriers still exist before myocardial gene therapy can spread to the field of
      routine clinical cardiology, including finding a safe vector allowing good
      transduction efficiency rates to cardiac myocytes when delivered through coronary
      arteries. In contrast, it is conceivable that in the open chest setting,
      myocardial gene therapy will rapidly be used by surgeons, by itself or in
      association with the injection of "wild" cells or cells transfected with various
      types of genes. It can now be assumed that such biotherapies will soon offer
      patients suffering from myocardial diseases (and especially heart failure) the
      perspective of major therapeutic progresses.

PMID- 11998336
TI  - Inflammation, cytokines and anti-inflammatory therapies in heart failure.
AB  - Both experimental and clinical studies have shown a role for inflammation in the
      pathogenesis of heart failure. This seems related to an imbalance between pro
      inflammatory and anti-inflammatory cytokines. Certain categories in patients with
      dilated cardiomyopathy have shown the presence of humoral and cellular immunity
      activation suggesting a possible relation between myocarditis and dilated
      cardiomyopathy. Recent studies suggest a link between the circulating levels of
      cytokines (TNF alpha IL-1 et IL-6), the clinical status and prognostic. However,
      the mechanisms connecting heart failure and cytokine activation are unclear and
      the sites of cytokines production remain controversial. In the clinical setting,
      specific measurements of cytokines are not available. As tests of inflammation,
      erythrocyte sedimentation rate and C-reactive protein concentration appear to
      have interesting pronostic values. Current conventional therapy i.e. ACE
      inhibitors, type I angiotensin II antagonist and beta-blockers have shown some
      anti-cytokine properties. Recently, immunosuppressive therapies have shown their
      ability to improve symptoms and LV ejection in selected patients with dilated
      cardiomyopathy and clear sign of myocardium inflammation. Specific anti-cytokine
      therapy have been developed and showed interesting results in preliminary
      clinical studies. However large clinical trials testing this new therapy have
      been stoppel prematurely because of deterious effects.

PMID- 11998337
TI  - [Long-term outcome of a patient with hypertrophic obstructive cardiomyopathy
      treated by alcohol septal transcoronary ablation].
AB  - We report here the long term follow-up of the first french case, at our
      knowledge, of alcohol septal transcoronary ablation in March 1998 in Clinique
      Ambroise Pare in an 76 year-old woman. This patient was in NYHA III-IV functional
      class and at control outflow gradient was 100 mmHg. She was prior treated with
      high dosis of beta-blockers then DDD-pacemaker with no effects on symptoms. The
      technique used was the one described by Sigwart and al., with injection of 3 cm3
      of ethyl alcohol in the first septal branch, after checking decrease of gradient
      during occlusion of septal branche with balloon angioplasty. After alcohol
      ablation, the gradient decreased immediately to 15 mmHg and disappeared at long
      term follow up. Three years and half after the procedure, no complication
      occurred, the patient remains asymptomatic and the control echocardiography shows
      interventricular septal reduction of thickness from 22 to 12 mm.

PMID- 11998338
TI  - [A rare cause of stroke in a patient with a cardiac pacemaker].
AB  - The authors report the case of a 78 year old woman admitted to hospital for
      recurrent cerebrovascular accidents, the initial investigation of which was
      normal. This pacemaker patient had a displacement of the definitive ventricular
      pacing catheter which was positioned in the left ventricle through a patent
      foramen ovale. The diagnosis was suspected on clinical and echocardiographic
      examination and confirmed by transthoracic and transoesophageal echocardiography.
      In view of the risk of systemic embolism, the pacing catheter was repositioned by
      an endovascular approach in the right ventricle.

PMID- 11998339
TI  - [Prevalence of decubitus lesions in a hospital in Lombardia].
AB  - A one day prevalence survey was performed in a University Hospital, with the aim
      of assessing the risk of developing a pressure sore by patients systematically
      assessed with the Waterlow Scale. Out of the 141 at risk patients, 16 had a
      pressure sore (11.3%). For six of them the sore was already present at admission
      so that the in hospital incidence was 7% (10 patients). Most at risk patients
      (74.4) were still cared on a standard mattress. The advantages and limits of
      prevalence surveys are discussed at the end of the three articles that present a
      prevalence survey, an incidence survey and the study of sentinel events.

PMID- 11998340
TI  - [The surveillance system of decubital lesions of the University Polyclinic in
      Udine: results of an incidence study].
AB  - A retrospective study of the incidence of pressure sores was one of the principal
      component of the ad hoc program of surveillance, prevention and treatment of
      pressure sores started in 1996 at University Hospital of Udine. Data were
      collected from the nursing records of patients defined at risk according to the
      Waterlow scale and admitted during 1998-99. Aims of the study were to quantify
      the number of patients who developed a pressure sore while in hospital and their
      risk level; stage of the lesions; to qualify the main risk factors and the
      management strategies adopted (i.e. mattresses, medications). Overall, 151
      subjects (20.7% of those recruited) developed a pressure sore the greatest
      majority (96%) were classified as transient and reactive redness or superficial
      sore, while 14 patients (4%) developed a severe sore. For 50.4% of the lesions a
      regression to a lower risk level or healing were documented.

PMID- 11998341
TI  - [The critical crux for moving from graduation to specialty degree].

PMID- 11998342
TI  - [Patients admitted with decubital lesions: the experience of the Milanese
      hospital in Garbagnate].
AB  - Patients may develop a pressure sore while in hospital, but some are admitted
      with a pressure sore. In Garbagnate hospital all patients are assessed for the
      risk of pressure sores. The ad hoc forms of patients with multiple lesions, in
      very poor conditions and with "sentinel" symptoms such as poor hygiene,
      malnutrition, bruises, are specifically assessed and further data from the head
      nurse and the family are collected to understand and reconstruct the patients'
      stories. From January 1999, 26 patients with pressure sores were admitted; 80%
      were over 75 years: 42.4% came from their homes and 7 from nursing homes. Half of
      the patients presented severe malnutrition. All the cases had some common
      characteristics: lack of well defined management of pressure sores; delays in the
      requests for special mattresses due to lack of attention or bureaucratic
      problems; or use of ineffective treatments or medications; lack of contacts
      between hospital and district, leading to a fragmented patient care. Two of the
      26 cases are presented and their significance discussed in details.

PMID- 11998343
TI  - [Exposure of nursing personnel to electromagnetic fields in neonatal intensive
      care].
AB  - Electromagnetic fields (EMF) are recognised as a source of environmental
      pollution for workers and people resident in exposed areas. The level of exposure
      to EMFs of the nurses working in the Siena Neonatal Intensive Care Unit, during
      two workdays was recorded and peak levels > 10 mG (1 microT) were registered well
      above an almost permanence exposure at > 2 mg G. The application of existing
      standard, cautionary criteria and rules would suggest protective or restrictive
      measures against EMF exposure for these workers.

PMID- 11998344
TI  - [Incidence, prevalence, sentinel events: comments on 3 studies about decubitus
      lesions].

PMID- 11998345
TI  - [Drugs in a full or an empty stomach?].

PMID- 11998346
TI  - [Fatma and the others].

PMID- 11998347
TI  - [Voice to the mothers, or all will be death].

PMID- 11998348
TI  - [Variability in the delivery of care in stroke units: analysis of the protocols].
AB  - In spite of the existing guidelines, the strategies and behaviours adopted in the
      care of the patients admitted to stroke units may vary widely across centres. The
      aim of this study was to quantify and quality the degree of real variability of
      the protocols enforced a sample of 13 of such units. There is no uniform
      behaviour for the monitoring of patients admitted with a stroke: vital signs are
      collected with different range intervals, i.e. blood pressure 15 for the first 6
      hours, from every 15 minutes to 2-3 hours. The assessment of dysphagia can be
      performed with the swallow test or having the patient drink a spoonful 10 ml of
      water, or 50 ml without stopping. The variability of behaviours is not, per se, a
      negative characteristic but it becomes a potential and unacceptable risk when
      solid evidences of effective practice are available. In the absence of clear cut
      recommendations the protocols should be defined trying to find a balance between
      effectiveness of the behaviours recommended and workload for nurses.

PMID- 11998349
TI  - [Pregnant and mentally incompetent].
AB  - Two women, aged 31 and 36 years, under treatment for schizophrenia and psychotic
      episodes, respectively, became pregnant and decided to discontinue their
      medication. Thereupon the psychiatric disorder recurred and they refused--i.e.
      they were unable--to consent to a proposed treatment or investigation regarding
      their pregnancies. The necessary consent had to be obtained from a legal
      guardian. This was the husband in the first, urgent case. In the second case
      approval from the judge was obtained for the patient to be admitted against her
      will to protect her life and that of the foetus. In the Netherlands obstetric
      intervention to protect the life of the mother or her unborn child is legally
      regulated by the Wet Bijzondere Opnemingen in Psychiatrische Ziekenhuizen (Act on
      Compulsory Admissions to Psychiatric Hospitals) and the Wet op de Geneeskundige
      Behandelingsovereenkomst (Act on Agreement Concerning Medical Treatment).

PMID- 11998350
TI  - [Interpretation of the increase in bovine spongiform encephalopathy outside Great
      Britain].
AB  - Outside Great Britain, the number of clinical cases of bovine spongiform
      encephalopathy (BSE) seems to be rising. It is unclear whether this increase is
      real, or whether it is caused by improved recognition and improved registration
      of BSE. A strict and independent control of the implementation of measures
      intended to keep human food free of the BSE agent is imperative.

PMID- 11998351
TI  - [Creutzfeldt-Jakob disease: diagnosis, incidence, prevention and treatment].
AB  - Creutzfeldt-Jakob disease (CJD) is a rare, neurodegenerative disorder belonging
      to the spongiform encephalopathies. A variant form (vCJD) is most likely the
      result of infection with the agent that causes bovine spongiform encephalopathy
      (BSE). Diagnostic information can be obtained by EEG, testing cerebrospinal fluid
      for the presence of the 14-3-3 protein, MRI, brain biopsy, tonsil biopsy, and
      postmortem brain examination. Some tests, such as MRI and postmortem brain
      examination, can be used to distinguish between CJD and vCJD. Pathological prions
      in a tonsil biopsy are only found with vCJD. In the Netherlands, there are four
      known cases of iatrogenic CJD. On the basis of certain exposure to BSE via the
      food chain, cases of vCJD are also to be expected. Chloropromazine and mepacrine
      are known to inhibit the formation of pathological prion conformations, but
      clinical trials have not yet been carried out.

PMID- 11998352
TI  - [The risk of variant Creutzfeldt-Jakob disease in the Netherlands and the effect
      of preventive measures].
AB  - Variant Creutzfeldt-Jakob disease (vCJD) is a fatal and untreatable neurological
      disease, in which pathogenic prions (PrPSc) are involved. There is convincing
      epidemiological and experimental evidence that vCJD is a human expression of
      bovine spongiform encephalopathy (BSE). The risk of transmission of pathogenic
      prions which cause vCJD to humans is influenced by the species barrier, genetic
      susceptibility of the host, dose of infection and route of exposure. Transmission
      of pathogenic prions from bovines to humans is possible through meat products
      containing nerve and lymphatic tissue, and through medical products derived from
      bovine material. Human to human transmission is, in principle, also possible via
      blood and blood-derived products, human organs and tissues for transplantation,
      and through surgical instruments. Preventive measures to reduce transmission from
      bovines to humans have been introduced step by step in the Netherlands since
      1989. With proper implementation, the current risk of becoming infected by Dutch
      meat products is small. It is very likely, however, that in the past decade BSE
      infected bovines have entered the food chain. The Dutch population has also been
      exposed to foreign infected meat products. Measures to prevent human to human
      transmission are currently being improved in the Netherlands. It is expected that
      cases of vCJD will occur in the Netherlands in the future, but the number cannot
      be estimated accurately. The presence of PrPSc in both the livestock and in the
      human population in the Netherlands constitutes a permanent public health threat
      and is a reason for continued vigilance and active prevention.

PMID- 11998353
TI  - [Diagnostic image (85). A man with ileus and an umbilical nodule. Sister Mary
      Joseph's nodule].
AB  - A 77-year-old man was admitted with an ileus. At physical examination a nodule
      was observed in the umbilicus, 'Sister Mary Joseph's nodule'. At laparotomy, this
      turned out to be a metastasis of obstructing left-sided colonic cancer.

PMID- 11998354
TI  - [Disinfection of the skin prior to injections does not influence the incidence of
      infections; a literature study].
AB  - OBJECTIVE: To assess the incidence of infections after subcutaneous,
      intramuscular or intravenous injections--using sterile needles--with or without
      prior disinfection of the skin. METHOD: Literature searches were made in the
      database Medline from 1966-June 2001, in the databases Picarta, Embase and the
      Cochrane Library, as well as manually in the reference lists of the collected
      articles. Original papers in English, Dutch or German were selected. RESULTS:
      Four relevant studies were found, generally of poor quality. In these two
      infections were reported after disinfecting the skin prior to over 2300
      injections in 156 patients, and none were reported after not disinfecting the
      skin prior to over 7000 injections in more than 700 patients. CONCLUSION: Both
      disinfection prior to skin injections and omission of disinfection were followed
      by (almost) no infections.

PMID- 11998355
TI  - [Sudden death following a single oral administration of haloperidol].
AB  - A 39-year-old man was admitted with myasthenia, alcoholic hepatitis and
      electrolyte abnormalities due to an inadequate nutritional state. On admission
      the ECG showed a prolonged QTc interval (0.46 s). The patient was treated with
      intravenous fluid and supplementary vitamins and minerals. On the third day of
      admission the patient developed a delirium, partly due to alcohol withdrawal, and
      was therefore treated with oxazepam 50 mg 3 times daily and a single dose of
      haloperidol 5 mg. One hour after ingesting haloperidol, the patient suddenly
      succumbed and resuscitation was not successful. The autopsy revealed a
      cardiomyopathy but no explanation for the sudden death. Due to the temporal
      relationship between the ingestion of haloperidol and this sudden death, we
      assume that haloperidol induced a fatal arrhythmia in the presence of a
      preexisting prolonged repolarisation time. To the best of our knowledge, sudden
      death after a single oral therapeutic dose of haloperidol has not previously been
      described.

PMID- 11998356
TI  - [Severe reversible dysphagia caused by herniation of the cerebellar ectopia].
AB  - A 58-year-old woman developed headaches and increasingly severe dysphagia over
      two years, which made her dependent on a nasogastric tube. Other symptoms were an
      unsteady gait and paraesthesias in the face, hands and feet. MR scanning of the
      craniospinal junction showed cerebellar ectopia with protrusion into the foramen
      magnum (Chiari I malformation). The patient recovered completely following
      surgical decompression. Previous reports show that this reversible cause of
      dysphagia is often not recognised until at a late stage.

PMID- 11998357
TI  - [Three patients with massive pulmonary embolism].

PMID- 11998358
TI  - [Less chance of a stroke by antihypertensive medication, regardless of blood
      pressure].

PMID- 11998359
TI  - [Lost in the methods (conclusion). XXXIX. The ultimate truth].

PMID- 11998360
TI  - [Adverse effects of passive smoking on the (unborn) child].

PMID- 11998361
TI  - [Adverse effects of passive smoking on the (unborn) child].

PMID- 11998362
TI  - [Congenital adrenal hyperplasia: clinical aspects and neonatal screening].

PMID- 11998363
TI  - [Chlamydial diseases of domestic animals--zoonotic potential of the agents and
      diagnostic issues].
AB  - The role of chlamydiae as agents of a number of important animal and human
      diseases is still the subject of intensive research. Recently, a proposal for
      taxonomic reclassification of this group of obligate intracellular bacteria was
      published, which was based on a large amount of new data on genetic relatedness.
      According to this proposal, the family Chlamydiaceae now comprises two genera
      (Chlamydia and Chlamydophila) with 9 largely host-related species. The previously
      accepted classification scheme had distinguished 4 species within the genus
      Chlamydia. The most important animal chlamydiosis with zoonotic character is
      psittacosis, a systemic disease in psittacine birds of acute, protracted, chronic
      or subclinical manifestation. The analogous infection in domestic and wild fowl
      is known as ornithosis. Avian strains of C. psittaci (new classification:
      Chlamydophila psittaci) can also infect humans, the symptoms being mainly
      unspecific and influenza-like, but severe pneumonia, endocarditis and
      encephalitis are also known. The main group of persons facing an elevated risk of
      infection includes those having frequent contact with domestic and companion
      birds at work or in their spare time. In Germany, the annual average of notified
      cases is approximately 100. Cases of transmission to humans were repeatedly
      reported in connection with enzootic abortion in sheep (causative agent: C.
      psittaci or Chlamydophila abortus, respectively). Various chlamydial species
      occur as pathogens and commensals as well in cattle, pigs, horses, and cats. The
      assessment of the actual epidemiological importance is, however, often difficult
      because of their almost ubiquitous spread. Likewise, those strains of C.
      pneumoniae (new classification: Chlamydophila pneumoniae) found in several animal
      species can not yet be assessed for pathogenic properties. The possibilities for
      diagnostic detection of chlamydiae have considerably improved following the
      introduction of molecular methods, particularly the polymerase chain reaction
      (PCR), which permits direct identification from clinical specimens and
      differentiation of species.

PMID- 11998364
TI  - [Will the effectiveness of the immunization of chicks with live Salmonella
      vaccines be affected by maternal antibodies?].
AB  - In the progeny of breeder birds which had been vaccinated with live Salmonella
      Typhimurium and inactivated Salmonella Enteritidis vaccines, the caecal and
      systemic colonisation by a live Salmonella Enteritidis and a live Salmonella
      Typhimurium vaccine was studied. The efficacy of the oral immunisation of chicks
      from vaccinated and non-vaccinated breeders with a live Salmonella Enteritidis
      vaccine on day 1 of age was studied by an experimental challenge with Salmonella
      Enteritidis on day 30 of age. Antibody production of isotypes IgG, IgA and IgM
      was determined in sera and jejunum of the birds. Vaccination of parent birds
      resulted in an increase of the antibody concentration in sera and jejunum of the
      chicks. Own antibody production after administration of the live Salmonella
      vaccine to the day-old chicks was not detected until day 21 of life. Compared to
      controls, the number of vaccine organisms in the caeca of the progeny of
      vaccinated breeder birds was reduced by 0.5-1.5 log10 units. The reduction of the
      Salmonella Enteritidis vaccine was more pronounced than that of the Salmonella
      Typhimurium vaccine. However, the reduced colonisation by the live Salmonella
      vaccine strain did not impair the efficacy of the immunisation of the chicks. To
      ensure efficacy of the active oral immunisation of chicks from vaccinated parent
      birds with attenuated live Salmonella vaccines also in case where amounts of
      maternally transferred antibodies are even higher, it should be guaranteed that
      chicks take in via drinking water the recommended dose of the vaccine strain. In
      this connection, factors like the low intake of drinking water by very young
      chicks, the concentration of the vaccine organisms in the water and the survival
      of the vaccine should also be considered.

PMID- 11998365
TI  - [Specificity of inhibition between Salmonella strains].
AB  - A phenomenon of inhibition among Salmonella organisms colonizing the gut of young
      animals can be demonstrated which is important in connection with immunization
      using live Salmonella vaccines. For practical utilization of this inhibition
      phenomenon, research into its specificity is very important. In vitro broth
      culture and animal experiments have shown inhibition to be genus-specific, i.e.
      there is no inhibition between strains of different genera of Enterobacteriaceae
      in most cases. The strongest inhibition occurs between isogenic (identical
      genotype) strains (strain-specific inhibition). This applies to Salmonella and
      other genera of Enterobacteriaceae. There was a close correlation between the
      degree of the inhibitory effect and the genetic relatedness of the strains, as
      has been demonstrated in Salmonella strains of different epidemiological
      classification. The inhibitory capacity was most pronounced among closely related
      strains. Clonal strains of Salmonella Enteritidis phage type 4 fully inhibited
      caecal colonization by Salmonella Enteritidis phage type 4 strains in 65% of the
      combinations tested in chicks. In broth culture experiments, the share of
      combinations with complete inhibition was above 90%. A significant inhibitory
      competence of a selected strongly inhibitory Salmonella Enteritidis phage type 4
      strain against the majority of Salmonella Enteritidis field isolates can be
      expected. However, Salmonella Enteritidis strains of all phase types showed
      almost no inhibitory competence against other Salmonella serotypes.

PMID- 11998366
TI  - [The influence of viscosity on adhesion and invasion of Salmonella strains in an
      in vitro model].
AB  - The influence of viscosity on the adhesion and invasion behaviour of Salmonella
      strains of different origin was investigated using an in-vitro-model. These
      processes seem to be strain-dependent. Compared to the controls, the number of
      internalized Salmonella was elevated. This increase was a result of the greater
      number of Salmonella which adhered to Caco-2-cells and was detected only for
      strains from organs of calves having died from salmonellosis. The average
      motility of these strains was determined to be 1.6 +/- 0.5 mm/h. A possible
      association between adhesion ability and motility was discussed.

PMID- 11998367
TI  - [Colonisation studies using Campylobacter jejuni in chicks].
AB  - White Leghorn chicks used in this study were hatched from specific pathogen-free
      eggs. The colonizing capability of Campylobacter (C.) jejuni strains was
      investigated in 6 experiments. The formation of specific antibodies associated to
      colonization was also detected. In each experiment, day of hatch chicks were
      randomly separated into three groups of 24 birds each: two groups colonized
      experimentally and one control group. Chicks were reared on the floor in three
      separated, adjacent rooms with sterilized wood shavings as litter. At 2 or 8 days
      of age, respectively, the chicks in the experimentally colonized groups received
      between 3.3 x 10(7) and 2.0 x 10(8) colony-forming units (CFU) of C. jejuni via
      oesophageal gavage. Furthermore, 7, 14, 21, 28, 42 and 56 days after inoculation,
      4 chicks of each group were sacrificed by cervical dislocation, at which time
      blood, liver and faeces were collected for processing. Serum was centrifuged and
      Campylobacter-specific IgG, IgA and IgM antibodies were measured by an indirect
      enzyme-linked immunosorbent assay (ELISA). Altogether, the colonizing capability
      of 11 C. jejuni strains was examined. Surprisingly, there were large differences
      between the C. jejuni isolates. After these experiments, we could divide the
      isolates into three groups. 4 out of 11 isolates could not be reisolated, 2
      isolates caused weak or delayed colonization and 5 C. jejuni produced strong,
      long-lasting colonization. In the first days of life (9 days), the C. jejuni-free
      SPF chicks (control animals) had high IgG titres in sera, which decreased
      markedly up to the age of 15 days. During the experiments the IgM and IgA titres
      remained nearly at the same level, i.e., the amounts of maternal antibodies were
      low and there was no evidence for antibody formation in the chicks themselves.
      Two- and 8-day-old chicks were inoculated with C. jejuni strain Penner 1. Two-day
      old chicks were colonized 3 weeks after inoculation. In comparison with these
      animals, 8-day-old chicks were colonized already 2 weeks after inoculation. There
      is the assumption, that the higher maternal antibodies in 2-day-old chicks could
      be responsible for this delay. In chicks the C. jejuni colonization resulted in a
      marked IgG (but not IgM and IgA) increase. Apparently, there is a positive
      relationship between the counts of this pathogen in caeca and the IgG increase.

PMID- 11998368
TI  - [Mixed infections of rotaviruses and Campylobacter jejuni in Caco-2 cells].
AB  - A mixed infection with rotavirus and 3 different Campylobacter jejuni strains was
      analysed in Caco-2 cells, a cell line highly susceptible to these pathogens. The
      results obtained showed no influence of the virus preinfection on the
      Campylobacter jejuni adhesion or internalisation in Caco-2 cells. Confocal laser
      scanning microscopy of mixed infected cells confirmed these results. The data
      from the present study indicate that specific rather than nonspecific mechanisms
      are involved in the interaction between rotavirus, campylobacter and host cells.

PMID- 11998369
TI  - [Progress in the replacement of animal experiments in the quality control of
      clostridial vaccines].
AB  - Animal experiments still play a central role in the quality control of vaccines.
      Generally, performance of these experiments is provided by law and laid down in
      the European Pharmacopoeia. Classical vaccines, the efficacy of which is
      calculated in International Units, require a very high number of experimental
      animals for quality control testing. The testing mainly consists of infection and
      intoxication experiments causing extreme suffering of the animals involved. This
      classical product group includes clostridial vaccines which are used to a great
      extent in veterinary medicine in particular. Within the last years, considerable
      efforts have been made to reduce the number of animal experiments in this field,
      lower the number of animals, and decrease the suffering of the animals during
      testing. Several research projects for the development and validation of
      alternative methods have been initiated. Furthermore, the 3R Concept
      (Replacement, Reduction and Refinement) is increasingly taken into consideration
      when developing or revising legal provisions. This led to various improvements
      regarding animal welfare in the quality control of clostridial vaccines.

PMID- 11998370
TI  - [The use of the toxin binding inhibition test for potency testing of Clostridium
      novyi type B alpha toxoid vaccines].
AB  - The toxin binding inhibition test (ToBI) were developed for potency testing of C.
      novyi type B alpha toxoid containing veterinary vaccines to replace the currently
      used toxin neutralisation test in mice (TNT). The antitoxin titres of rabbit sera
      (AN-, HV- and SP sera) were determined with ToBI using the international
      reference serum with known antitoxin titre. In order to show the validity of the
      methods, the results were compared with those of the manufacturers/regulatory
      authorities and correlation coefficients were calculated. The correlation
      coefficients were r = 0.93 (AN sera), r = 0.73 (HV sera) and r = 0.85 (SP sera).
      All correlations were statistically significant. The specificity of the methods
      could be proved using heterologous antisera. The results of the ToBI were
      reproducible. Thus, the ToBI offers a suitable in vitro method for the
      determination of the antitoxin titre of rabbit antisera as an alternative to the
      toxin neutralisation in mice for potency testing of vaccines containing C. novyi
      type B alpha toxoid.

PMID- 11998371
TI  - [Consequences of short term fluctuations of environmental temperatures in calves-
      Part 1: Immediate reactions of the respiratory system, the cardiovascular system,
      metabolism and thermal regulation].
AB  - Clinically healthy calves (aged 3-6 weeks) were exposed to defined ambient
      temperature for 4 hours (cold: 5 degrees C, 60% humidity, n = 12; warm: 35
      degrees C, 60% humidity, n = 11). During the exposure of each animal in a
      climatic chamber, certain parameters of lung function, respiratory mechanics,
      blood gas analysis, circulation, metabolism and thermal regulation were
      registered simultaneously in order to study immediate physiological consequences
      of different environmental conditions. In comparison to control calves (18-20
      degrees C, 60% humidity, n = 13) an insufficient adaptation of these young calves
      was noticed in both cold and warm conditions. At 5 degrees C, marked changes in
      lung function were observed, i.e. airway constriction, pulmonary hypertension,
      and ventilation-perfusion-mismatching leading to hypoxemia and hypercapnia. Due
      to compensation by the circulatory system, a sufficient O2-consumption of the
      organism as well as an unchanged body temperature were maintained. At 35 degrees
      C, the respiratory pattern changed to panting and a higher dead space
      ventilation. No changes were observed in pulmonary gas exchange and blood
      arterialisation. Due to hyperventilation, the partial pressure for CO2 decreased
      in blood. Since the body temperature increased continuously, thermal regulation
      was insufficient. This situation would have led to animals collapsing after a
      period of heat stress lasting longer than 4 hours. In conclusion, young calves up
      to the age of 6 weeks were not able to tolerate acute changes in ambient
      temperature. This was true for cold conditions (5 degrees C) as well as for hot
      conditions (35 degrees C). The results of this study should be taken into account
      in order to optimise transport and farming conditions.

PMID- 11998372
TI  - [Consequences of short term fluctuations of the environmental temperatures in
      calves--Part 2: Effects on the health status of animals within three weeks after
      exposure].
AB  - The aim of the present study was to examine consequences of sudden changes in
      ambient temperature over a 4-hour period (see part 1 [ELMER & REINHOLD, 2002]) on
      respiratory health in clinically healthy calves. Therefore, the relationship
      between short-term changes in ambient temperature and the occurrence of clinical
      respiratory disease was checked over a period of 3 weeks after exposure in 10
      calves exposed to 5 degrees C, in 9 calves exposed to 35 degrees C and in 8
      control calves (kept at 18-20 degrees C). Within the period beginning 3 days
      before exposure and lasting until up to 21 days after exposure, each calf was
      examined clinically. Rectal temperature and respiratory rate were measured daily.
      All calves were euthanised on day 21 after exposure. Macroscopically visible
      pneumonic lesions were evaluated using a semiquantitative system. Tissue samples
      from tonsils, bronchi, trachea, lung and mediastinal lymph nodes were examined
      bacteriologically. In contrast to non-exposed control calves, severe respiratory
      illness was observed in individual calves of both exposed groups (5 degrees C, 35
      degrees C). Significant increases in body temperature, respiratory rate and
      animal losses (2 calves died in the group exposed to 5 degrees C, one calf died
      in the group exposed to 35 degrees C) were the main clinical findings. At
      necropsy (3 weeks after exposure), no pneumonic lesions were observed in control
      calves--despite the fact that this group had the highest microbiological
      colonisation rates in tonsils and in large airways, i.e. trachea and bronchi,
      within all groups. However, variable pneumonic lung lesions were seen in
      remaining calves exposed to cold or warm air (5 degrees C, 35 degrees C). The
      microbiological examination confirmed that mainly Mycoplasma spp. were identified
      in the lung tissue of calves exposed to 5 degrees C while Pasteurella multocida
      and/or Mannheimia haemolytica were the only germs found in the lung tissue of
      calves exposed to 35 degrees C. The results of parts 1 and 2 of the present study
      related to health issues of calves should be taken into account for future
      legislation on animal welfare.

PMID- 11998373
TI  - [In vitro studies into the influence of ochratoxin A on the production of tumor
      necrosis factor alpha by the human monocytic cell line THP-1].
AB  - The influence of pure OTA and an Aspergillus-ochraceus crude toxin on the
      intracellular expression and the secretion of tumor necrosis factor (TNF) alpha
      by the monocytic cell line THP-1 was studied in vitro. After 4 hours exposure,
      the secretion of TNF alpha was inhibited to 50% by pure OTA in a concentration of
      400 ng/ml and by crude toxin in a concentration of 100 ng/ml. The same
      concentrations of mycotoxins impaired the mitochondrial activity of THP-1 cells
      only marginally. The intracellular expression of TNF alpha was not disturbed by
      pure OTA in the concentrations tested, whereas crude toxin showed an inhibitory
      effect. The possible reasons for these findings are discussed.

PMID- 11998374
TI  - Cytokine mRNA expression in experimental porcine pneumonia.
AB  - A porcine Pasteurella multocida (P. m.) infection model was established to study
      the spatial distribution of cytokine mRNA-expressing cells in lung tissue during
      acute pneumonia. The mRNA detection was performed by non-radioactive, formamide
      free in situ hybridization (ISH) using oligonucleotides against the porcine
      interleukins (IL): IL-1 beta, IL-2, IL-4, IL-6, IL-8, TNF alpha and TGF beta.
      Cytokine mRNA-expressing macrophages were demonstrated by a double staining
      procedure combining immunohistochemistry (IH) using the primary antibody 2G6 with
      IL-1 beta, IL-6 and TGF beta ISH. With the exception of some stained TNF alpha
      expressing cells, no IL mRNA was detectable in the lung of unaffected animals.
      The experimental P. m. pneumonia was characterized by a predominant, exudative
      and an additional proliferative interstitial component as well as abscess
      formation in the lung. Many cells of the region between the abscess membrane and
      the affected lung area showed high IL-6, IL-1 beta, IL-4 as well as TGF beta and
      few cells low IL-8 mRNA expression with characteristic distribution patterns. The
      ISH/IH double staining procedure revealed that at least some of the IL-6 or TGF
      beta-producing cells belonged to the 2G6-positive macrophages.

PMID- 11998375
TI  - [Modern approaches to choice of anesthesia in children].
AB  - The advantages and disadvantages of intravenous and inhalation anesthesias in
      pediatric anesthesiology are analyzed. Causes of complications induced by
      myorelaxants and measures for preventing these complications are discussed. Basic
      protocols of intravenous or inhalation anesthesias with the minimum fresh gas
      flow for pediatric anesthesiology are presented.

PMID- 11998376
TI  - [On the technology of performing sacral anesthesia].

PMID- 11998377
TI  - [Use of H2-receptor blocker famotidine (quamatel) in anesthesiology for
      cardiopulmonary bypass surgery].
AB  - The efficiency of perioperative therapy with quamatel (histamine H2-receptor
      blocker) for preventing gastrointestinal complications in cardiosurgical patients
      was evaluated. Quamatel was used in 68 cardiosurgical patients subjected to
      aortocoronary bypass surgery for coronary disease. Perioperative pH profile of
      the gastric contents was evaluated by a Gastroscan-5 acidogastrometer (Russia).
      The volume of gastric juice secretion was evaluated after induction anaesthesia,
      at the end of operation, and 6-8 h after the intervention. Quamatel was highly
      effective and well tolerated by cardiosurgical patients with concomitant
      gastrointestinal diseases during preparation to surgery. Use of quamatel for
      premedication, particularly in patients with gastrointestinal diseases,
      stabilized pH and decreased the gastric juice hypersecretion during the entire
      intraoperative and early postoperative period, thus preventing gastrointestinal
      complications. High therapeutic efficiency of quamatel and its good tolerance
      recommend it for cardiosurgical patients and to surgical patients of other
      profiles for prevention of gastrointestinal complications.

PMID- 11998378
TI  - [Evaluation of the efficacy of anesthesiologic protection in induced abortion].
AB  - The efficiencies of modern intravenous anesthetics, analgesics, and hypnotics
      (dormicum, diprivan, ketamine, and fentanyl) in various combinations for
      artificial abortions was evaluated. Hemodynamic parameters, autonomic status, and
      clinical signs of awakening were evaluated. The most effective protection was
      attained with a combination of diprivan, dormicum, and fentanyl.

PMID- 11998379
TI  - [Central hemodynamics in conditions of combined intravenous anesthesia using
      propofol and ketamine in pediatric ophthalmology].
AB  - A total of 152 patients aged 4-14 years at risk of ASA I or II were examined.
      Planned operations were carried out: correction of myopia, strabismus, and eyelid
      ptosis. The patients were divided into 4 groups: 1) 54 patients operated on under
      combined anesthesia (propofol infusion and ketamine bolus), 2) 60 children
      operated on under combined anesthesia by ketamine and propofol infusions, 3) 24
      patients operated on under ketamine + seduxene infusion narcosis, and 4) 34
      children in whom ketamine and seduxen were injected in boluses. All operations
      were carried out under conditions of spontaneous respiration. Central hemodynamic
      parameters were studied by tetrapolar chest rheography with NCCOM3-R7 device
      (BIOMED). Methods of combined anesthesia with diprivan (propofol) are indicated
      for children subjected to ophthalmological surgery as methods with the minimum
      effects on the hemodynamics and ensuring adequate anesthesiological protection as
      regards the clinical and hemodynamic status.

PMID- 11998380
TI  - [Clinical significance of the procalcitonin test in differential diagnosis of
      systemic inflammatory reaction in pancreatonecrosis].
AB  - The significance of procalcitonin test (PCT) in the differential diagnosis of
      sterile and infectious pancreonecrosis was evaluated. Twenty-four patients with
      destructive pancreatitis were examined. Plasma procalcitonin concentrations were
      increased in the patients with infectious pancreonecrosis and correlated with the
      clinical status of patients evaluated by APACHE II and SOFA scores. The
      sensitivity and specificity of this test in the diagnosis of infectious
      pancreonecrosis were 84.4 and 83.3%, respectively, its prognostic significance
      being as high as 93.1%. Plasma concentrations of procalcitonin in sterile
      pancreonecrosis were normal or slightly increased. These results indicate that
      measurement of procalcitonin concentrations is an optimal laboratory test for
      differential diagnosis of sterile and infectious pancreonecrosis. PCT helps
      determine the treatment strategy in patients with various forms of destructive
      pancreatitis.

PMID- 11998381
TI  - [Intensive care of children with DIC syndrome based on the use of low molecular
      weight heparins].
AB  - The first section of this paper presents data on low-molecular-weight heparins:
      pharmacokinetics and pharmacodynamics, advantages in comparison with common
      heparin. The second section presents the results of fraxiparin and clivarin use
      in 43 children aged 9 months to 14 years with acute/subacute DIC syndrome of
      infectious origin. Therapeutic and maintenance doses, the mode of injection of
      low-molecular-weight heparins, and methods for laboratory monitoring of their
      efficiency and safety are presented.

PMID- 11998382
TI  - [Peritoneal dialysis in acute renal failure in children].
AB  - Data on the treatment of infants with acute renal failure are presented.
      Indications for renal substitute therapy are enumerated and hemodialysis and
      peritoneal dialysis are compared. Complications of peritoneal dialysis are
      discussed and methods for their treatment are presented. The authors demonstrate
      that peritoneal dialysis is an effective, safe, and available method for treating
      acute renal failure in infants.

PMID- 11998383
TI  - [Use of perfluothane as a component of neurorehabilitation therapy in the acute
      period in patients with craniocerebral injuries].
AB  - The effects of perfluothane on the course of posttraumatic period are evaluated
      in patients with craniocerebral injuries. Forty patients were divided into 2
      groups treated and not with perfluothane. Hemodynamics, hemostasis, gaseous
      exchange and lung ventilation functions, and neurological status were evaluated
      over the course of treatment. The data evidence a favorable effect of
      perfluothane on the course of the posttraumatic period in patients with
      craniocerebral injuries.

PMID- 11998384
TI  - [Method of biphasic defibrillation in modern electropulse therapy].
AB  - Cardiovascular diseases, primarily coronary disease, remain the leading cause of
      mortality in the majority of countries with well-developed economy. Electropulse
      therapy (defibrillation) is the main method helpful in life-threatening
      arrhythmias leading to heart arrest. The development of devices generating
      biphasic pulses is in progress now. Clinical trials confirmed the capacity of a
      bipolar pulse to arrest cardiac arrhythmia with current of lower strength in
      comparison with monopolar pulses. Due to low discharge energy, the degree of
      postresuscitation myocardial dysfunction is essentially decreased. New technology
      of biphasic pulses developed by Schiller AG Firm (Switzerland), based on the use
      of Multipulse Biowave device, is a new step in development of urgent care
      potentialities in severe cardiac arrhythmias in risk groups.

PMID- 11998385
TI  - [Inhalation anesthesia with halogen-containing anesthetics in children].
AB  - The study was carried out in 158 children aged 3-16 years operated on in an
      inpatient setting. The patients were divided into 3 groups with different types
      of induction narcosis: 1) ethrane inhalation up to 3 vol% and N2O with O2 in 1:1
      ratio (56 pts); 2) fluothane up to 3.5 vol% and N2O with O2 in 2:1 ratio (87
      pts), and 3) isoflurane inhalation up to 3 vol% and N2O with O2 in 1:1 ratio (15
      children). Central hemodynamics, cardiointervalograms, and external respiration
      function were studied. Ethrane and isoflurane induction was longer (4-12 min)
      than fluothane induction (3-5 min). Anesthesia with ethrane and isoflurane in
      combination with N2O with O2 led to a less pronounced reaction of the central
      hemodynamics than fluothane anesthesia, which led to a decrease of the sympathic
      tone and increase in the activity of the parasympathetic component of the
      autonomic nervous system. Analyzing a vast scope of clinical material on the use
      of inhalation anesthetics and all the pros and contras, the authors conclude that
      inhalation anesthetics can be used in children.

PMID- 11998386
TI  - [Character and risk factors of bacterial colonization of newborns in intensive
      care units].
AB  - A total of 116 newborns treated in intensive care wards were examined. The
      incidence, type, and risk factors of bacterial colonization were evaluated. Only
      7.8% patients were colonized with gram-negative polyresistant microflora by
      admission, while after 3 days of intensive care as many as 48.2% newborns were
      colonized. The major microorganisms were Pseudomonas aeruginosa, Klebsiella spp.,
      and Enterobacter spp. A relationship was detected between the bacterial spectrum
      of the skin and mucosa and the agents of infectious inflammatory complications in
      the newborns. The most significant factors of risk of colonization in the
      newborns with antibiotic-resistant gram-negative bacteria in intensive care wards
      were forced ventilation of the lungs and initially severe clinical status (CRIB
      score 5 and higher).

PMID- 11998387
TI  - [Intraoperative infusion-transfusion therapy in pediatric surgical oncology].
AB  - Modern concept of intraoperative blood loss compensation differs crucially from
      the old rule to compensate the blood loss by donor blood in the same volume,
      which is explained by serious risks associated with blood transfusions. The
      parameters of infusion/transfusion therapy with 6% Infucol GEK are presented. The
      drug was used with good results in adults and children. Volemic parameters are
      presented and dynamic changes in the blood clotting system after transfusion of
      infucol GEK and Russian colloid preparation polygluquine are analyzed. Infucol
      GEK improved vascular blood filing and decreased the volume of other preparations
      used for blood loss compensation.

PMID- 11998388
TI  - [Cardiac tamponade as a complication of central line catheterization in
      newborns].
AB  - Two cases with cardiac tamponade in neonates, one of which eventuated in death,
      are presented. The total tamponade rate was 0.27%. Several hours after
      catheterization patients suddenly developed bradycardia, hypotension, and signs
      of decompensation, all within an hour. One patient died and the diagnosis was
      made at autopsy. In the other patient ultrasonography showed a clear echo-free
      space between the epicardium and pericardium, with the tip of the catheter in
      contact with the atrial wall. Percutaneous pericardiocentesis was performed under
      cardiographic guidance; 11 ml of hemorrhagic fluid containing 26 mmol/liter
      glucose were aspirated. The catheter tip was then repositioned to the vena cava
      superior. Hemodynamic status rapidly improved and this patient survived. A review
      of relevant publications is offered.

PMID- 11998389
TI  - [Bispectral index (BIS)--a new ideology in solving an old problem].
AB  - A new method of electroencephalogram (EEG) processing is discussed: bispectral
      index (BIS), used for monitoring the depth of total anesthesia. The technology of
      BIS estimation is a principally novel approach to EEG processing, which can be
      denoted as an expert conclusion. EEG monitor Aspect A-100 (Aspect Medical System,
      USA) has been used for 3 years in the operation room during narcoses with
      barbiturates, propofol, midasolam, fentanyl, calypsol, isoflurane, and nitric
      oxide. BIS is a convenient and reliable method for evaluating the depth of total
      anesthesia with anesthetics with pronounced hypnotic effects at all stages of
      surgery. The disadvantages of the method are enumerated. The authors claim that
      monitors designed for expert evaluations hold good promise.

PMID- 11998390
TI  - [Monitors, monitor-computer and information systems for resuscitation and
      intensive care words (state of the problem)].

PMID- 11998391
TI  - [Ways to reduce mortality of newborns with developmental defects].
AB  - Technological progress contributed to progress in surgery on the newborns.
      However, despite the progress in surgery and intensive care of the newborns, the
      results of treatment of patients with congenital defects are sometimes
      disappointing. The priority problems for today are the respiratory distress
      syndrome, hemodynamic disorders, and renal dysfunction, which can be united into
      the syndrome of general dysadaptation of the newborns. Based on experience gained
      in the treatment of newborns in pediatric surgical hospital, protocols of
      treating newborns with developmental defects (congenital diaphragmatic hernia,
      esophageal atresia, and gastroschisis) have been developed. These protocols are a
      stage and a prerequisite for development of more effective methods for treating
      such patients. Common intensive care should be supplemented by such important
      measures as maintenance of adequate temperature regimen at all stages of medical
      transportation and therapy of a newborn, obligatory preoperative preparation for
      stabilization of vital functions, multicomponent endotracheal anesthesia, use of
      inotropic agents (dopamine and dobutrex), synchronic prolonged artificial
      ventilation of the lungs and prolonged analgesia, limitation of indications to
      the use of blood preparations and wide use of hydroxyethylated starch solutions
      in infusion therapy, rational antibiotic therapy with constant monitoring of the
      microecological status, and early detection and correction of concomitant
      diseases. Solution of these problems will essentially decrease the postoperative
      mortality of newborns with developmental defects.

PMID- 11998392
TI  - [Changes in hemodynamics with a combination of epidural anesthesia and propofol
      sedation in children].
AB  - Hemodynamic profiles and myocardial contractility were investigated in children
      aged 3-14 years during epidural anesthesia with propofol. Anesthesia was induced
      by intravenous bolus propofol (3.5 mg/kg). Ketamine (2.4 mg/kg) was used to
      potentiate analgesia during intubation. Xilocaine (5 mg/kg) was used for epidural
      analgesia. Anesthesia was maintained by continuous i.v. propofol infused in a
      dose of 191-312 micrograms/kg x min (mean dose 243 +/- 30.3 micrograms/kg x min)
      until the peak of epidural analgesic activity was reached, after which propofol
      dose was gradually reduced to 53-143 micrograms/kg x min (mean 108.8 +/- 14.6
      micrograms/kg x min). This variant of epidural anesthesia with i.v. propofol
      ensured a hemodynamically stable anesthesia and good analgesia in operations of
      any complexity. It was however paralleled by a moderate decrease of myocardial
      contractility.

PMID- 11998393
TI  - [An unexpected effect of ketamine during administering anesthesia to a child].

PMID- 11998394
TI  - [Etiology, epidemiology and classification of sepsis in children].

PMID- 11998395
TI  - [Anesthesiologic support of videothorascopic operations in children with pleural
      empyema].
AB  - Total anesthesia for videothoracoscopic operations in children with pleural
      empyema is difficult because of severe clinical status and single-lung
      ventilation. Hemodynamics, blood gases, and oxygen transport were studied in 35
      children aged 1.5-14 years with ASA class II-III. Total anesthesia with diprivan
      (propofol) in combination with fentanyl and myorelaxant mivacurium was used. The
      modes of single-lung ventilation depended on bronchial intubation type.

PMID- 11998396
TI  - [Regularities of fixation of brain serum antibodies from patients with lateral
      amyotrophic sclerosis in rabbit CNS].
AB  - Kuhns' indirect immunofluorescent test was used to study fixation of serum brain
      antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral
      amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is
      characterized by formation of brain Ab complementary to various structures of
      nervous and glial cells, myelin of fibers from different conducting systems,
      vessels which exhibit both common and individual antigenic properties. It was
      found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar,
      cervicothoracic and lumbosacral LAS in different CNS structures varies.

PMID- 11998397
TI  - [Action of regulators of peripheral cholinergic processes on development of early
      arrhythmia in myocardial ischemic rats].
AB  - Occlusion of the left coronary artery in rats provoked ventricular tachycardia
      (VT) and ventricular fibrillation (VF) within the first 30 min of ischemia
      leading to death in 20% animals. Methacin (i.v., 100 micrograms/kg) significantly
      prolonged VT and VF without effects on the survival. Acetylcholine (i.v., 10
      micrograms/kg/min) had no influence on VT frequency and severity but prevented
      VF. Rats from this group survived. The same effect was observed for neostigmine
      (i.v., 25 micrograms/kg). Nicotine (i.v., 2.5 micrograms/kg/min) prolonged VT
      episode duration but did not change frequency and severity of VF and survival.
      Ganglioblockers hexametony and azametony (i.v., both in a dose 500 micrograms/kg)
      significantly attenuated VT, prevented VF and death of the animals. Thus,
      cholinotropic drugs may have both antiarrhythmic and proarrhythmogenic effects in
      early arrhythmias induced by ischemia.

PMID- 11998398
TI  - [Influence of opiate analgetic prosidol on cerebrospinal neurons and ganglia
      (experimental study)].
AB  - Morphological, histochemical and histoenzymological changes in nervous tissue of
      the spinal cord and ganglium after epidural introduction of narcotic analgetic
      prosidol were studied in acute experiment on 12 mongrel dogs. Compared to control
      animals, no negative prosidol effects were found on the neuron structure and
      microcirculatory bed of nervous tissue. The changes in the control and test
      animals were of the same type in different parts of nervous system (spinal cord
      and ganglium).

PMID- 11998399
TI  - [Hemosorption in serotherapy (serosorption) in experimental acute diphtheric
      toxemia with the use of affinity sorbents].
AB  - In modeling acute diphtheric toxemia in guinea pigs, the authors propose to
      perform hemosorption using selective sorbents under continuous introduction of
      antitoxic immune sera into extracorporeal contour in front of sorption column.
      Combination of hemosorption with serotherapy in the same time interval may be
      denoted as serosorption. As specific sorbents, affine preparations imasorb A-700
      and Imasorb G-700 were used. They selectively eliminate from the blood flow CIC
      produced by diphtheric toxin (anatoxin) and antitoxic rabbit and horse
      antibodies. Changes in the titers of the diphtheric toxin (anatoxin) and CIC in
      blood evidence for efficiency of selective sorbents were confirmed by
      immunohistochemical analysis of the preparations' granules after hemoperfusion.

PMID- 11998400
TI  - [General pathology of man as a basis for clinical thinking, its role in medical
      science and education].

PMID- 11998401
TI  - [Thiol-selective mechanism of in vitro interaction of serum proteins with
      adrenaline in IHD patients].
AB  - The author demonstrates that patients with ischemic heart disease have
      phenomenological peculiarities of adaptation by stability of thiol-dependent
      mechanism of structural-functional condition of blood serum proteins; describes
      the phenomenon of emergence of free nonprotein SH-groups in protein-free reaction
      mixtures of the serum varying in adrenaline concentrations in unstable angina
      pectoris (this phenomenon indicates structural-functional destabilisation of
      serum proteins and adequate immunopathological process); suggests an alternative
      method and pathogenetic diagnosis of IHD clinical forms in which thiol-containing
      analytes serve as molecular markers.

PMID- 11998402
TI  - [Mechanisms of an antioxidative action of erythrocytes in experimental
      ophthalmoherpes infection].
AB  - Experimental ophthalmoherpes infection activates free-radical oxidation in red
      cells from rabbit and rat peripheral blood, inhibits catalase activity, enhances
      activity of superoxide dismutase demonstrating changed antioxidative defense at
      early stages of herpes infection.

PMID- 11998403
TI  - [Assessment of cardiovascular function in small laboratory animals (rats) using
      diagnostic computer complex Diastom-01].

PMID- 11998404
TI  - [Opiatergic modulation of cardiac resistance to arrhythmogenic exposures].

PMID- 11998405
TI  - [Therapeutic effects of a new taurine derivative in chronic hepatic diseases].
AB  - Therapeutic properties of a novel taurin N-phenylakyl derivative (TAU-15) in a
      dose 25 mg/kg were studied in male rats on models of chronic toxic hepatitis and
      partial hepatectomy. A hepatoprotective action of TAU-15 was established which is
      due to antioxidative action of TAU-15 and its ability to normalize protein
      synthetizing activity of hepatocytes.

PMID- 11998406
TI  - [Effects of hemiextirpation of gonadal glands on the conditioned reflex avoidance
      behavior in male and female rats].
AB  - A comparative analysis has been made of the influence of hemiextirpation of the
      gonadal glands on realization of conditioned-reflex activity in rats of both
      sexes. Learning was assessed in active and passive avoidance paradigms. It was
      established that hemigonadectomy in male rats or hemiovariectomy in female rats
      fail to modify acquiring and reproducing active avoidance and passive reactions
      as compared to the controls. It is suggested that hemiextirpation of the gonadal
      glands does not significantly influence realization of conditioned-reflex
      activity in rats of both sexes.

PMID- 11998407
TI  - [Ethical dilemmas in the sharing of information in the care of HIV-infected
      children].
AB  - Ethical dilemmas are regularly encountered in the care of patients infected with
      HIV (Human Immunodeficiency Virus), especially in issues regarding professional
      confidentiality and shared information with the child and his/her family as well
      as among professional health workers. This communicable disease, which can be
      treated but not yet cured, leads to exclusion, due to the fear of infection, to
      its severity and induces stigmatisation of affected individuals. It interferes
      with life projects, sexuality, reproductive health, family life, projection into
      the future. In HIV paediatrics, practitioners regularly deal with complex
      situations and need to balance parental authority and children's
      needs/dependence, respect of patient's confidentiality and hazards to another
      person's health, potential negative impact of disclosing information and risks
      attributable to the lack of information.

PMID- 11998408
TI  - [Ethical aspects of parent-adolescent conflicts: about dignity].
AB  - The work in Psychiatry of children and adolescents at the general hospital in
      paediatric and emergency services--where we have to meet any kind of children and
      adolescents, either hospitalized or only consulting--makes us discover clinical
      situations in which we must consider the whole life context of those young
      patients. Our experience shows that, within the problems and conflicts of the
      adolescent period, ethical questions concerning beliefs, values, ideals, hopes
      and prohibitions ... are, in paradoxal ways, underlying the constitution of the
      symptoms we are required to cure. If we respectfully pay attention to those
      aspects, we can help to increase choice possibilities, and we can contribute to
      overtake conflicts and difficulties. The ethical position for health workers
      could be to help the patient and his (her) family to regain their self esteem and
      dignity according to their own values and history.

PMID- 11998409
TI  - [Ethics and long-term nutritional support in children].
AB  - Since its outset, parenteral nutrition has led to deep ethical thinking. These
      interrogations have increased over the last 30 years when faced with the problems
      brought about by the concept of intestinal failure and parenteral nutrition
      dependence, by the quality of life of these children and the endeavors to wean
      them from this artificial nutrition at the price of major therapeutic innovation.
      Thirty years later, regulated programs of home parenteral nutrition and of
      intestinal (and liver) transplantation instigate new ethical interrogations. It
      is the expert's responsibility to take these points into account when making
      strategic choices which he will then discuss with the families.

PMID- 11998410
TI  - [Ethical aspects of organ transplantation with living related or unrelated
      donors].
AB  - Organ transplantation with living donor, relatively not much used in France,
      raises a number of ethical questions. It just transgresses the principle of
      primum non nocere, transgression finally accepted when considering the potential
      benefit for the sick recipient. It is only possible to use a living donor if a
      free informed consent is given. This raises some questions and supposes for the
      doctor in charge the obligation to follow a strict protocol. Commercialization is
      in the heart of the ethical discussion about living donors. This is universally
      condemned, but quite largely used in some underdeveloped countries and we are
      faced now to some professionals arguing in favour of the extension of this
      practice in Occident. Recently, a new category of donors has appeared, the
      altruists: they are ethically acceptable if strictly defined, but this category
      raises also some problems.

PMID- 11998411
TI  - [Genetic screening in children].
AB  - Before giving a prescription on a genetic test, it is necessary to estimate if a
      real direct benefit exists for the children. This is right if the disease occurs
      during childhood and teenage and when the genetic status identified early may
      improve care, prevention and people accompaniment or if, on the contrary, knowing
      that the children has no risk to develop a disease will save him from a
      particularly restricted medical observation. At the opposite, letting him know
      his future may, for sure, cause him some trouble (disruption). The parents'
      distress and their hope for getting a negative test result should not be more
      important than the child's interest which has to prevail over his parents'. If
      the child has no risk to develop a genetic disease himself and if the risk
      concerns only his descendants, there is no reason for knowing his genetic status
      before he makes plans himself for his procreation.

PMID- 11998412
TI  - [Ethical dilemmas for end-of-life decisions in the perinatal period].
AB  - According to several recent surveys, around 50% of the deaths occurring nowadays
      in French neonatal intensive care units result from a medical decision. This has
      led French neonatologists to set up guidelines for end-of-life decisions and
      practice in the perinatal period, which are presented in this paper. It covers
      definitions, clinical situations, ethical principles, obligations of the medical
      and nursing staff.

PMID- 11998413
TI  - [Intractable neonatal heart diseases: a controversy].
AB  - A congenital heart disease is said intractable when the only options are either
      heart transplantation or a complex palliative programme including several
      interventions leading to a mid-term Fontan-type circulation. The latter uses the
      single ventricle as a systemic one while the pulmonary circuit is a non-pulsed
      one which by-passes the absent right ventricle through a cavo-pulmonary
      anastomosis. Both of these are difficult to operate and have hazardous long term
      results. This is why prenatal detection of such lesions usually leads to
      termination of pregnancy. Yet, postnatally, a serious ethical issue emerges,
      opposing the above-mentioned options to a third way: abstention. Information
      delivered to the parents plays here a crucial role in decision making and
      everybody agrees for the need of the greatest objectivity. But to achieve such a
      wish is terribly challenging since many socio-cultural factors may puzzle the way
      to deliver and to receive the main messages. This can easily be demonstrated by
      the well-known instance of hypoplastic left heart syndrome.

PMID- 11998414
TI  - [Reaching a team consensus in pediatric oncology when treatment proves
      ineffective].
AB  - Modern treatments are able to cure 3/4 of paediatric cancers, but on another hand
      there is still a too high number of patients which will enter a resistant phase
      and test the ability of the medical and nursing team to face together the new
      modalities of care. At diagnosis, the reasonable hope to cure the child and the
      exciting feeling to be endued with a repairing mission strengthen among the team
      both the self-esteem and a rational and emotional consensus. Conversely, at the
      time of relapse or resistant disease, the feeling of a failure, added to anxiety
      and reciprocal aggressiveness, will contradictorily affect the group. In this
      atmosphere of loss of control of reality and emotions, elaborating new priorities
      of care is mandatory: medical positions have of course to be in keeping, but this
      is not enough since the nursing team has, through sharing information and
      feeling, to give their cure project of the child's cancer as lost while retaining
      and expanding their ability to care the child with cancer. Thanks to an over
      investment of the symptomatic, psychological, and affective help support to the
      child, the nursing team will succeed in regaining this self-esteem absolutely
      necessary to their own professional survival. Consensus in the team is ultimately
      linked to its empathic ability of exchanging with the families which in turn
      results in giving them guidelines for the last weeks and months of life and
      helping them to be less emotionally unprovided when bereavement time has come: a
      pedagogy of the continuity of care is thus taking place which, equally distant
      from forsaking and therapeutic relentlessness, chooses to give up the idea of
      curing in order to go on caring.

PMID- 11998415
TI  - ["Conservative" treatment in the multiply handicapped child].
AB  - The increasingly medicalized strategies of nursing for the multihandicapped
      children point out the problem of limits and constraints of these processing.
      First, a review of methods of treatments for the evolutionary complications is
      done. Secondly, the consequences of the choice of these therapeutics are
      discussed. The ethical consequences of the various processing are analysed by
      developing the motivations of the caring teams, the concepts of quality of life
      and its dualism with dignity of life.

PMID- 11998416
TI  - [Special aspects of pediatric research relevant to the advisory board of
      protection of biomedical research participants].
AB  - In France, biomedical research is under regulation of the law on the Protection
      of people who participate in biomedical research, passed on December 20th, 1988
      (Huriet's law). This law appears difficult to apply in some useful
      investigations, specially in paediatrics. Several points are discussed here with
      propositions for easier procedures.

PMID- 11998417
TI  - [Maternal-fetal hemostasis and cerebral palsy].

PMID- 11998418
TI  - [Vesico-ureteral reflux in children: current aspects and recommendations].

PMID- 11998419
TI  - [Retinopathy of prematurity: 10-year retrospective study at the University
      Hospital of Strasbourg].
AB  - OBJECTIVES: This work was splitted in two parts: the first one was the study of
      retinopathy incidence in premature infants less than 33 weeks gestation, born
      between 1988 and 1997; the second one is the identification of severe retinopathy
      different risk factors. PATIENTS AND METHODS: Our study was retrospective over
      ten years. All premature infants less than 33 weeks gestation born between
      January 1, 1988 and December 31 1997, admitted to the Strasbourg neonatal
      intensive care unit with retinopathy, were included (164 children). First we
      studied the incidence evolution of retinopathy over these ten years; then by a
      statistical study (univaried and multivaried) we looked for a significant
      difference for several factors between the infants with mild retinopathy and the
      group with severe ocular disease. RESULTS: Retinopathy incidence decreased in ten
      years from 13.7 to 6.7% for the moderate forms (P < 0.001) and from 3.7 to 1.7%
      for severe stage (non significant). A significant difference was found for
      various factors after comparison between both groups. The birth weight (P = 5 x
      10(-4)), the gestational age (P = 4 x 10(-6)), were weaker in the group with
      severe retinopathy. A maternofetal or nosocomial infection (P = 0.009; P =
      0.002), hemodynamic shock (P = 10(-6)), patent ductus arteriosus (P = 10(-6)),
      bronchopulmonary dysplasia (P = 3 x 10(-6)), postnatal steroid treatment (P =
      0.007), respiratory distress syndrome (P = 0.01), were all more frequent in the
      severe retinopathy sample. The number of days with oxygenotherapy (P = 10(-6))
      and mechanical ventilation (P = 10(-6)) the number of blood transfusion (P = 10(
      5)) were higher in this group than in the other. The logistic regression analysis
      showed that the hemodynamic parameters influence mostly on the risk of severe
      ocular disease, like an hemodynamic shock syndrome (OR = 16.94; CI = 2.12-135.77)
      or a patent ductus arteriosus (OR = 5.36; CI = 1.53-18.74). CONCLUSION: A
      decrease of the retinopathy incidence in premature infants was observed in ten
      years, probably due to better care in the neonatal period. An unstable
      hemodynamic state would be one prominent risk factor in the genesis of severe
      retinopathy of prematurity.

PMID- 11998420
TI  - [Procalcitonin and viral meningitis: reduction of unnecessary antibiotics by
      measurement during an outbreak].
AB  - OBJECTIVE: Viral meningitis are often treated with antibiotics in emergency
      because routine analysis of CSF is not always efficient for distinguishing
      between viral and bacterial infection. The aim of the study was to evaluate the
      usefulness of procalcitonin (PCT) to reduce antibiotic treatments. METHODS AND
      RESULTS: A blood PCT level < 0.5 ng/mL was prospectively used for the diagnosis
      of viral origin of meningitis in 58 patients (two months-14 years), in which
      enterovirus was isolated by culture or PCR during an outbreak (May-June 2000).
      CSF cells range was 10 to 2800/mL (m: 244), PMN 5 to 2464/mL and CSF proteins
      range was 0.19 to 0.92 mg/dL (m: 0.37). Seventeen patients received antibiotic
      therapy in admission. In nine patients, PCT (dosage was routinely measured
      3/week) result < 0.5 ng/mL was obtained in 24 h and in 48 h in six: treatment was
      then stopped and children led hospital. In two patients, PCT was > 1 ng/mL
      because of bacterial coinfection. CSF and PCT values were similar to those of an
      already published control group. CONCLUSION: PCT dosage allowed to shorten
      hospitalization of 4.47 (controls) to 2.06 (patients) days in patients receiving
      unnecessary antibiotic treatments. During this outbreak, PCT dosage allowed to
      reduce 40 days of hospitalization.

PMID- 11998421
TI  - [Raynaud's syndrome in children. Study of 23 cases].
AB  - AIM OF THE STUDY: To analyze the epidemiological characteristics of Raynaud's
      syndrome in childhood. PATIENTS AND METHODS: We conducted a nine-year
      retrospective survey of children up to 17 y seen with Raynaud's syndrome. Charts
      were retrieved from pediatrics and dermatology outpatient units, and from the
      registry of capillaroscopy. A specific questionnaire was designed and missing
      data were completed after a phone interview of the parents. RESULTS: A definite
      diagnosis of Raynaud's syndrome was ascertained in 23 patients with marked female
      predominance (SR = 0.27). Triggering factors were essentially a cold environment
      and emotions. The mean age at the diagnosis was 11 y (5 to 16 y) with an onset
      after ten years in 65% of cases. Eleven of these Raynaud's syndromes were
      secondary with ten connectivitis, eight remained essential and four were
      suspected to be secondary. DISCUSSION: This series of pediatric Raynaud's
      syndromes was important according to scarcity of literature on this topic. The
      diagnosis is made upon exclusive clinical basis and we underline the high
      frequency of serious underlying conditions. Further etiologic investigations are
      mandatory for any pediatric patient with Raynaud's syndrome. The sensitivity
      (78%) and specificity (80%) of capillaroscopy were of interest in our patients;
      its prognosis value needs to be evaluated in a larger group of patients.

PMID- 11998422
TI  - [Imported malaria in children in 1999. Study of the Armand-Trousseau Hospital in
      Paris].
AB  - METHODS: Eighty children were treated at the hospital Armand-Trousseau (Paris,
      France) for a malaria attack from 1999-01-01 to 2000-02-01. RESULTS: The
      parasites were: Plasmodium falciparum: 87.5%, Plasmodium malariae: 12.6%,
      Plasmodium ovale: 10%, Plasmodium vivax: 6.3%. Mean age was 8.1 years (range:
      three months to 15 y). The origin of patients was: West Africa for 60 children,
      Central Africa for ten children and Comores for seven. Sixty-six patients
      suffered from common malaria attack and seven children were admitted with a
      presentation of severe malaria. The severe attacks were cerebral malaria for six
      cases, associated with severe anemia in five cases; the 7th child had a
      respiratory distress (ARDS) and died. The other six cases were cured without
      sequelae. Relapses were observed for eight patients: one after a severe cerebral
      malaria, six after a common P. falciparum attack, one after a P. ovale attack.
      Parasitemia was higher than in preceding years (mean 2.9%) and more than 5% in 11
      cases, but without clear link with severity. Treatment by halofantrine with a
      single cure was followed by five relapses. None of those children received an
      effective prophylaxis during and after travel (55/80 without any prophylaxis).
      CONCLUSION: These data emphasize the importance of a good appraisal of criteria
      of severe malaria and lead to advice hospitalization of children with malaria in
      temperate zone.

PMID- 11998423
TI  - [Twin-twin transfusion syndrome: report of two cases with hemodynamic
      complications].
AB  - CASE REPORTS: We report two cases of cardiac dysfunction in twin-twin transfusion
      syndrome (TTTS) evaluated with serial echocardiography. Two cases of TTTS were
      referred at 27 and 26 weeks. At delivery at 31 weeks, the first recipient twin
      had evidence of severe cardiac dysfunction with decreased ventricular function
      and transient systemic hypertension. There was polycythaemia. Favorable outcome
      was observed after treatment with arterial vasodilating (nicardipine) and
      inotropic agents (dobutamine, enoximone), and reduction of haematocrit. At 28
      weeks the other recipient twin had cardiac dilatation with hypokinetic
      myocardium. These alterations were cured by dobutamine. CONCLUSION: These cases
      show that even severe cardiac dysfunction may be reversed after birth unlike in
      utero natural evolution.

PMID- 11998424
TI  - [Home environment and acute propylene glycol intoxication in a two-year old. An
      unusual case report].
AB  - BACKGROUND: Acute propylene glycol intoxication in a two-year-old toddler
      underlines the potentially serious toxicity in children of this chemical agent
      present as a diluent in many drugs and environmental products such as cosmetics,
      diapers, cleansing towels, despite a common consideration of safety and lack of
      toxicity. CASE REPORT: A two-years-old boy previously healthy was found in the
      morning by his parents in his cradle, lethargic, responsive only to sharp pain.
      On admission, vital signs were: temperature 38.5 degrees C, lethargy, polypnea;
      propylene glycol intoxication through disposable cleansing towels chewing was
      ascertained by anamnesis and blood urine analyses which revealed metabolic
      acidosis and serum propylene glycol peak. CONCLUSION: Environmental acute
      propylene glycol intoxication must be considered and searched for in front of a
      metabolic acidosis case of unknown origin in children.

PMID- 11998425
TI  - [Acute non-traumatic mediastinitis].
AB  - Acute mediastinitis is uncommon. When it occurs, it usually follows an esophageal
      perforation or thoracic surgery. CASE REPORT: We report on a case of a ten-year
      old girl with non traumatic mediastinitis secondary to a pleuro-pulmonary
      infection due to Klebsiella pneumoniae.

PMID- 11998426
TI  - [Long-term followup of primary intestinal lymphangiectasia in the child. Six case
      reports].
AB  - Primary intestinal lymphangiectasia induce symptoms of protein-losing
      gastroenteropathy. Only very few studies evaluate the long term follow up of such
      patients. We reviewed six children diagnosed at 17 +/- 12 months and followed for
      11 +/- 4.9 years. CASE REPORTS: As soon as the diagnosis was made the patients
      were submitted to a strict low fat diet with added medium chain triglycerides and
      intermittent liposoluble vitamins perfusions. The diet allowed the disappearance
      of symptoms for all the patients but laboratory findings indicated continuing
      chyle leak for most of the children. Only one child who had normal biological
      parameters tolerates a normal diet since four years. Relaxation of the diet by
      two patients who had moderate hypoalbuminemia and lymphopenia led to severe
      clinical relapses 14 and 17 years after the diagnosis period with therapeutic
      difficulties. Three patients with long term strict low fat diet remain
      asymptomatic. CONCLUSION: In most asymptomatic patients, the underlying lymphatic
      defect remains with permanent biological abnormalities. Clinical relapses may be
      severe and difficult to treat; thus the need for dietary treatment appears to be
      permanent.

PMID- 11998427
TI  - [Mechanisms of hepatic fibrogenesis].
AB  - Hepatic fibrosis is a scaring process leading to cirrhosis, a major complication
      of numerous chronic liver diseases. Hepatic stellate cells play a central role in
      the fibrotic process. After parenchymal or biliary injury, cytokines and growth
      factors allow the recruitment, proliferation, and activation, of stellate cells
      toward myofibroblasts, which secrete the extracellular matrix. Fibrosis,
      resulting from the failure of the balance between synthesis and degradation of
      extracellular matrix, is an evolutive and potentially reversible process.
      Histological examination is the main investigation to quantify fibrosis.
      Serological tests are warranted to allow a non invasive follow up of patients.
      Development of antifibrotic therapies should soon permit to slow down the
      evolution toward cirrhosis, limiting the needs for hepatic transplantation.

PMID- 11998428
TI  - [Primary molecular changes and secondary biological problems in Bartter and
      Gitelman syndrome].
AB  - Bartter syndrome and Gitelman syndrome are primary hereditary diseases
      characterized by hypokaliemia, alkalosis, hypertrophy of the juxtaglomerular
      complex with secondary hyperaldoteronism and normal blood pressure. They result
      from molecular disorders leading to a defect of sodium reabsorption in
      respectively the Henle's loop and the distal convoluted tubule. Biological
      adaptations of downstream tubular segments, i.e. distal convoluted tubule and
      collecting duct, are responsible for hypokaliemia, alkalosis, renin-aldosterone
      activation, prostaglandins hypersecretion and dysregulation of the urinary
      excretion of calcium and magnesium, illustrating the close integration of the
      regulation of different solutes in the distal tubular structures.

PMID- 11998429
TI  - [Antenatal diagnosis of ovarian cyst: perinatal management].
AB  - More than 85% of prenatal ovarian cysts have a follicular or luteal origin. Their
      natural history is a spontaneous involution. However, adnexal torsion resulting
      in the loss of the ovary can occur at any time of the evolution. Pre and
      postnatal changes in the sonographic aspects allow to choose the appropriate
      therapeutical indications: conservative approach, laparoscopic surgery, or
      percutaneous aspiration. Prenatal aspiration must be avoided. The last prenatal
      sonographic examination should be performed as close as possible from the end of
      the gestation, and the first postnatal echography within the first 24 hours of
      life. Surgery of prenatal complicated cysts has to be planned a few days after
      birth. Uncomplicated prenatal cysts will be treated depending on size and
      echographic patterns at birth.

PMID- 11998430
TI  - [Porphyria and drugs].
AB  - Porphyrias are the result of inherited enzymatic defects of the heme's
      biosynthesis chain. A porphyria crisis with abdominal pain and neurological or
      psychiatric signs may be precipitated by drugs. Our purpose is to list the main
      drugs which may precipitate phorphyria crisis, specifying which are
      contraindicated such as cefalosporins, anaesthetics, anti epileptic and anti
      tubercular drugs, and which are doubtful because of conflicting results published
      in literature. In any case it is necessary to verify any prescription before
      giving a drug to a patient with porphyria.

PMID- 11998431
TI  - [Anorexia nervosa and severe malnutrition: nutritional practice guidelines in
      pediatrics].
AB  - The nutritional care of a severely emaciated anorexic adolescent can be performed
      in any pediatric ward. This article is a practical guide which reminds the
      indications, mostly clinical, for hospitalization and the way to achieve a
      progressive but efficient renutrition. We wish to share our own practical
      experience while focusing on acute nutritional care, according to the aim of this
      section of the journal.

PMID- 11998432
TI  - [Erythema multiforme].

PMID- 11998433
TI  - [Giant hemangioendothelioma of the parotid gland in an infant].

PMID- 11998434
TI  - [End-of-life decisions in the perinatal period].

PMID- 11998435
TI  - [Prevalence of Helicobacter pylori infection in nurseries in the Paris region].

PMID- 11998436
TI  - [Heart rate variability in infants with obstructive sleep apnea].

PMID- 11998437
TI  - [Antibiotic sensitivity of bacteria responsible for acute meningitis in children
      in Libreville (Gabon)].

PMID- 11998438
TI  - [Reflections of stopping curative therapy in pediatric oncology: Ariane and
      Icare].

PMID- 11998439
TI  - Recent advances in antineoplastic principles of Traditional Chinese Medicine.

PMID- 11998440
TI  - Synthesis and cytotoxic activity of new 2,4-diaryl-4H,5H-pyrano[3,2-c]benzopyran
      5-ones on MCF-7 cells.
AB  - A series of eight halogenated 2,4-diaryl-4H,5H-pyrano[3,2-c]benzopyran-5-ones
      have been synthesized, characterized and their stereochemistry determined. In a
      second stage of our work, the reported molecules were tested for their
      antiproliferative activity on MCF-7 breast carcinoma cells. Pharmacological
      results were compared with those of diethylstilbestrol (DES), an estrogen, as
      well as ICI 182,780, a pure antiestrogen. Then, these derivatives were evaluated
      for their capacity to activate the transcription of a reporter gene and for their
      affinity for human recombinant estrogen receptors alpha (hER alpha). These
      results were compared with those of coumestrol, a phytoestrogen structurally
      close to 2,4-diaryl-4H,5H-pyrano[3,2-c]benzopyran-5-ones, and with RU 58668, a
      pure antiestrogen. Although these derivatives exhibit a significant
      antiproliferative activity higher than that of ICI 182,780, neither of them
      displayed a significant estrogenicity or an affinity for hER alpha. Such results
      may suggest that their antiproliferative activity is not dependent of an
      antiestrogenic response.

PMID- 11998441
TI  - Syntheses and biological evaluation of indole-2 and 3-carboxamides: new selective
      cyclooxygenase-2 inhibitors.
AB  - A series of indol-2 and 3-carboxamides were prepared and evaluated for their
      ability to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1).
      Substitution on indol nitrogen with benzyl and p-fluorobenzyl group of indole-2
      carboxamides 8, 10, 11 provides fairly active COX-2 enzyme inhibitors.

PMID- 11998442
TI  - [Pyrrolo(2,3-c)quinolines and pyrrolo(3,4-d)quinolines--synthesis and
      investigation of lipoxygenase inhibition].
AB  - The Paal-Knorr synthesis of the cyclic hemiketonacetal 4 yields the pyrrole-2,4
      dicarboxylic acid diesters 1c and 7 via the cyclic hemiaminals 5 and 6; while the
      pyrrole-2-carboxylic acid ester 9 is formed from the 1,4-diketon 10. Under
      reducing conditions 1c and their 4-carboxylic acid 8 give the pyrrolo[3,4
      c]quinoline carboxylic acid ester 2a; the cyclic hydroxamic acid 11 and the
      lactam 12 of the pyrrolo[2,3-c]quinoline type are obtained from compound 9. The
      isomeric compounds of the pyrrolo[3,4-c]quinoline series 16, 17 and 18,
      respectively, are synthesized from the pyrroles 14 and 15; the cyclic hemiacetal
      13 was used as educt. The tricyclic hydroxamic acids 16 and 17 weakly inhibit the
      5-lipoxygenase (IC50 > 10 microM, relating to the formation of LTB4 of human
      whole blood).

PMID- 11998443
TI  - Nonaqueous capillary electrophoretic analysis of hexetidine in a commercial
      liquid formulation.
AB  - A non-aqueous capillary electrophoresis method has been proposed to analyse
      hexetidine and its degradation products in a commercial liquid pharmaceutical
      formulation. The separation was achieved using a 37 cm fused silica capillary
      with a 75 microns internal diameter, an electrolyte of 120 mM sodium acetate
      buffer in methanol, at 16 kV and 25 degrees C. The results show that the proposed
      method is able to resolve hexetidine from its degradation products and/or
      impurities.

PMID- 11998444
TI  - Replacement of cyanogen bromide solution PH. EUR. with 1,3-dibromo-5,5
      dimethylhydantoin (DBH). Analytical methods of pharmacopoeias with DBH in respect
      to environmental and economical concern, Part 13.
AB  - PH. EUR. 2002 identifies nicotinamid, nicotinic acid, and nikethamide according
      the reaction of Konig using cyanogen bromide solution prepared with bromine water
      and ammonium thiocyanate immediately before use. This colour reaction can be
      better performed with 1,3-dibromo-5,5-dimethylhydantoin (DBH) and sulphanilic
      acid as condensation component. The prescriptions of PH. EUR. have been improved
      in respect to environmental and economical concern.

PMID- 11998445
TI  - Stability of the new antileukemic 4-pyranone derivative, BTMP, using HPLC and LC
      MS analyses.
AB  - The stability of the new antileukemic kojic acid derivative, 5-benzyloxy-2
      thiocyanatomethyl-4-pyranone (BTMP) was investigated. The degradation of BTMP was
      studied using specific and reproducible HPLC and LC-MS methods. Accelerated
      stability studies of BTMP were conducted in 0.1 M hydrochloric acid solution,
      physiological phosphate buffer solution (pH 7.5) and basic phosphate buffer
      solution (pH 9.0) at 30, 40 and 60 degrees C, respectively. The degradation of
      BTMP was found to follow pseudo-first order kinetics. In basic solution (pH 9.0)
      BTMP underwent rapid hydrolysis at a degradation rate constant (0.183-0.638 h-1)
      and degradation half-life (3.67-1.06 h) depending on the temperature setting. On
      the other hand, BTMP was significantly stable in 0.1 M hydrochloric acid solution
      (kdeg: 0.0017-0.0052 h-1; degradation half-life t1/2: 408.6-135.7 h), whereas in
      physiological phosphate buffer solution (pH 7.5), BTMP was only moderately stable
      (kdeg: 0.006-0.231 h-1; degradation half-life: 117.7-3.0 h). Arrhenius plots were
      constructed to predict the degradation kinetic parameters of BTMP at 25 degrees C
      and 4 degrees C. LC-MS analyses confirmed the degradation of BTMP in basic
      solutions and indicated at least two degradation products; namely 5
      benzyloxypyran-2-ol-4-one (m/z 217.8) and 2-thiocyanatomethylpyran-5-ol-4-one
      (m/z 181.6).

PMID- 11998446
TI  - Optimization and performance evaluation of peptide-loaded monolithic poly-epsilon
      caprolactone microspheres in mice bearing melanoma B16F1.
AB  - The objective of this investigation was to develop a bleomycin depot based on
      monolithic microparticulate technology to suppress tumour growth and to maintain
      constant plasma drug concentrations within an optimal therapeutic window over a
      prolonged period of time. Formulations were optimized with biodegradable poly
      epsilon-carpolactone and evaluated in vitro for physicochemical characteristics,
      drug release in phosphate buffered saline (pH 7.4) and evaluated in vivo in
      tumour bearing mice. This investigation revealed that upon subcutaneous
      injection, the biodegradable depot-forming poly-epsilon-carpolactone microspheres
      controlled drug release and suppressed tumour growth kinetics significantly
      compared to control. A preliminary pharmacokinetic evaluation exhibited steady
      plasma drug concentrations during the study period. This formulation with its
      reduced frequency of administration and better control of drug disposition is
      expected to provide an economic benefit to the user compared with products
      currently available for chemotherapy.

PMID- 11998447
TI  - Dendrimer grafts for delivery of 5-fluorouracil.
AB  - Polyamidoamine (PAMAM) dendrimers were prepared by linking methyl methacrylate
      and ethylenediamine successively on an amine core. Surface modification of PAMAM
      dendrimer was done by fatty acid grafting converting them to a unimolecular
      micellar system (Dendrimer grafts). IR, 1H NMR, 13C NMR studies confirmed the
      structure. The drug 5-fluorouracil (5-FU) was entrapped in dendrimer grafts. The
      effects of various solvents (ethanol, dichloromethane, tetrahydrofuran), pH and
      ionic strength on solubilization of 5-FU were determined. Phospholipid was
      further coated on the dendrimer grafts. The product was lyophilized and obtained
      as yellowish-white powder. Average particle size was ca. 375 nm as determined by
      Malvern's Mastersizer 4. Drug loading was ca. 53% by weight. Stability studies
      were conducted for 1 month at room temperature and 40 degrees C, where the
      systems were relatively stable. Release rate was sustained across cellulose
      tubing in PBS. In vivo studies were performed in albino rats and pharmacokinetic
      parameters and bioavailability were determined from the plasma profile of 5-FU.
      The phospholipid coated dendrimer graft formulation was found to be more
      effective orally than free drug. The lymphatic uptake was also increased
      indicating absorption of the developed formulation through the lymphatic route.

PMID- 11998448
TI  - Effects of ascorbic acid and sodium selenite on growth and redifferentiation in
      human hepatoma cells and its mechanisms.
AB  - After being treated with ascorbic acid (AA) 3 mM + sodium selenite (SS) 1.5
      microM, the growth rate and mitotic index of human hepatoma cells BEL-7402
      decreased remarkably. The indexes related to cell malignancy were improved, such
      as cell surface charge obviously decreased, the electrophoresis rate fell from
      1.76 microns.s-1.V-1.cm-1 to 0.93, the average of alpha-fetoprotein (alpha-FP)
      content decreased from 341 micrograms.g-1 protein to 92, and gamma-glutamyl
      transpeptidase (gamma-GT) activity from 0.76 U.g-1 protein to 0.19. The indexes
      related to cell differentiation were affected favourably, such as the level of
      tyrosine-alpha-ketoglutarate transaminase (TAT) activity increased from 14.2
      mumol.g-1 protein to 49.0, and the colonogenic potential decreased 95.3%. These
      results indicated that hepatoma cells had been successfully induced to
      redifferentiation by AA + SS. The activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GPX) were significantly higher, while the activity of
      catalase (CAT) was slower in the treated group than in the control group. The
      malondialdehyde (MDA) content decreased slightly, reduced glutathione (GSH)
      decreased sharply, and H2O2 content increased dramatically. In conclusion, these
      results indicate that the combination of ascorbic acid and sodium selenite may
      induce the redifferentiation of hepatoma cells and inhibit cell growth by virtue
      of enhancing the activities of antioxidative enzymes and reducing the formation
      of H2O2, and altering the cell redox status. The combination of ascorbic acid and
      sodium selenite may be a potent anticancer treatment option for human hepatoma
      cells.

PMID- 11998449
TI  - The usefulness of a biosensor controlled perfusion cell culture for the
      investigation of new drugs demonstrated with the marine fungus
      Kirschsteiniothelia maritima.
AB  - The investigation of new biological active substances from limited sources for
      example from marine organisms needs sensitive and evident test systems. Such a
      system is the glucose biosensor controlled perfusion cell culture. The glucose
      consumption of cells is a very sensitive parameter which allows the continuous
      measurement of external effects of test substances on the cells under in vivo
      like conditions. Cytotoxic concentrations of active substances as well as a virus
      infection lowers the glucose consumption of continuously perfused cells. This
      effect can be monitored using a glucose biosensor. The influence of drugs and the
      virus infection can be observed simultaneously in the same system continuously
      over several days. With two substances isolated from the marine fungus
      Kirschsteiniothelia maritima investigations for cytotoxic and for antiviral
      effects are demonstrated.

PMID- 11998450
TI  - New sesquiterpenes from Ligularia macrophylla.
AB  - From the roots of Ligularia macrophylla, a bisesquiterpene, ligumacrophyllal (1),
      and an eremophilane sesquiterpene, ligumacrophyllatin (2) were isolated. Their
      structures were elucidated by 2D-NMR herein. Additionally, seven known compounds
      (3-9) were afforded from the plant, and compound 3 was found as natural product
      for the first time.

PMID- 11998451
TI  - New isopimarane diterpene and new cineole type glucoside from Nepeta prattii.
AB  - Together with sixteen known compounds, a new isopimarane diterpene (prattol) and
      a new cineole type glucoside were isolated from Nepeta prattii. Their structures
      were elucidated on the basis of spectral methods as isopimar-15-en-3 beta,8
      beta,20-triol, and (1R, 2R, 4S)-1,8-epoxy-p-methan-2-O-beta-D-glucopyranosyl(1-
      >6)-beta- D-glucopyranoside.

PMID- 11998452
TI  - New terpenoids from Haplopappus multifolius.
AB  - The chemical investigation of the aerial parts of Haplopappus multifolius
      afforded the new monoterpene 2,9-epoxy-p-menth-6-en-8-ol (7, haplopappol), the
      new monoterpenoid ester 9-cis-p-coumaroyloxy-alpha-terpineol (8, haplofolin), the
      new diterpene 18-hydroxylabda-7,13Z-dien-15-oic acid (6) and its known E-isomer
      (5). In addition, the known dihydroflavones 3',5-dihydroxy-4',7
      dimethoxydihydroflavone and 3',4',5-trihydroxy-7-methoxydihydroflavone and the
      known dihydroflavonols 3',5-dihydroxy-4',7-dimethoxydihydroflavonol and 3',4',5
      trihydroxy-3-acetyl-7-methoxydihydroflavonol were also obtained. The structural
      assignments of these compounds were made possible by the different spectroscopic
      measurements.

PMID- 11998453
TI  - Two new naphthalene and anthraquinone derivatives from Asphodelus tenuifolius.
AB  - Chromatographic separation of an ethanolic extract of rhizomes of Asphodelus
      tenuifolius Cav. (Asphodelaceae) yielded in addition to beta-sitosterol,
      stigmasterol and two anthraquinone derivatives, 1,8-dimethoxynaphthalene as well
      as two new naphthalene derivatives. The new compounds were identified as 2-acetyl
      8-methoxy-3-methyl-1-naphthol and 2-acetyl-1,8-dimethoxy-3-methylnaphthalene. The
      separated compounds were identified on the basis of IR, MS, 1H and 13C NMR data.

PMID- 11998454
TI  - Are there computers in your life?

PMID- 11998455
TI  - Diagnosis and management of acute and chronic prostatitis.
AB  - Prostatitis syndromes are some of the most poorly understood yet prevalent
      problems in urology. There is little controversy over acute prostatitis, a
      urinary tract infection with systemic symptoms and signs that typically responds
      to antimicrobial therapy. By contrast, the chronic prostatitis syndromes have so
      far eluded attempts to understand their pathophysiology and design effective
      therapies, resulting in great frustration among patients and health care
      providers. An accurate diagnosis and a multidisciplinary approach are essential
      to assist men with this often debilitating condition.

PMID- 11998456
TI  - Bladder neck obstruction in the female.
AB  - Bladder neck dysfunction is a rare cause of obstruction in women. The symptoms
      are nonspecific and diagnosis relies on video-urodynamic evaluation. In this case
      study, a woman presented with urinary retention, recurring urinary tract
      infections, and bilateral hydronephrosis, in whom video-urodynamics revealed
      bladder neck obstruction. Her clinical presentation, as well as the pertinent
      literature on the diagnosis and treatment of bladder neck obstruction in women,
      are reviewed.

PMID- 11998457
TI  - Quality of life post radical prostatectomy: a male perspective.
AB  - The purpose of this qualitative study was to explore the meaning and effect of
      urinary incontinence and impotence on the quality of life for men with prostate
      cancer. The Cancer Recovery Model guided the study. This model is based on the
      assumption that the chronicity of cancer is a function of recovery as well as
      illness and focuses on the strength of an individual to regain his powers of
      survival until death. The study identified indicators for quality of life for men
      who have had a radical prostatectomy for cancer that should be included in
      developing discharge teaching plans and reinforced in community followup.

PMID- 11998458
TI  - Psychometric analysis of the Broome Pelvic Muscle Self-Efficacy Scale in African
      American women with incontinence.
AB  - There is a paucity of research on African-American women and incontinence.
      Previous research has demonstrated that pelvic muscle exercises can reduce or
      eliminate incontinence in women. This methodological study reports findings about
      incontinence, self-efficacy, depression, and quality of life in African-American
      women with incontinence. This study further reports the psychometric analysis of
      the Broome Pelvic Muscle Self-Efficacy Scale in this population.

PMID- 11998460
TI  - Study shows common UTI bacteria are most susceptible and least resistant to
      ciprofloxacin.

PMID- 11998461
TI  - Effectiveness of 3 vs. 7 day therapy cited.

PMID- 11998462
TI  - Professional golfers drive awareness for bladder health.

PMID- 11998463
TI  - [Opinions of nursing assistants about shift reports].
AB  - It approaches the nursing assistants' opinion about the importance of shift
      report in the continuity of nursing assistance. It aims to find subsidies that
      can contribute to a better development of this activity in the nursing practice.
      It is a descriptive research that uses an opinion poll with 15 nursing assistants
      of one clinical unit of a university hospital in Porto Alegre/RS. The data were
      collected through a questionnaire with closed questions and one open question.
      The data analysis of the closed questions was done by a manual tabulation of the
      obtained answers, and they were grouped by regularity and repetition. The data
      treatment of the opened question was through the thematic analysis with
      categories construction and contents quantification. It was possible to verify
      that the study subjects are interested in changing aspects related to the
      activity. It was emphasized the need to greater objectivity in the information
      transmission and in the time reduction.

PMID- 11998464
TI  - [Daily work problems and their relationship with self-care and care of others].
AB  - The authors analyse daily problems of the nurses' work and the coping strategies
      used, building knowledge about self care and care of the others in administrative
      spaces that emphasize freedom and autonomy, relating this (re)construction
      process to their health process Starting from semi-structured interviews with
      nurses of a University Hospital, it was possible to identify problems related to
      human and material resources, team relationship and nurses' own characteristics
      of subjectivity. There is a perception of greater freedom and autonomy related to
      administration, although the nurses perceive negative aspects about the
      boundaries of the freedom exercises, with commitment to the care of the other.

PMID- 11998465
TI  - [Solidarity relationships in health services -- utopia?].
AB  - The article approaches some aspects considered relevant to rethink relations on
      the care offered by health services, especially, hospital organizations. It
      presents some reflection upon the possibilities of constructing human civility,
      centered on solidarity relations and on the exercise of citizenship, on an
      ethical condition of a dignified and healthier life. Mutual comprehension between
      human beings is vital to restore life, nature and conviviality values.

PMID- 11998466
TI  - [Changes in professional practice of nurses at a teaching hospital in the inner
      Sao Paulo, as a result of the emergence of HIV/AIDS].
AB  - This investigation was conducted with the purpose of identifying the changes in
      the professional practice of nurses at a public teaching hospital as a result of
      the arrival of HIV/AIDS. Through interviews with 100 nurses it was found that 76
      (76%) referred changes in their professional practice. Of these, 52 (68.4%)
      referred to the use of garments; 17 (22.3%) to continuing education; and 7 (9.2%)
      to nursing care. Of a total of 76 reasons presented by the nurses, 46 (60.5%)
      were related to fear of becoming infected; and 30 (39.5%) related to nursing
      care. The study revealed that the advent of HIV/AIDS has risen various changes in
      practical activities of nurses, especially in those related to garments, having
      as the main concern the fear of becoming infected. Continuing education programs
      that aim not only to identify the causes that determine low adherence to standard
      precaution measures and undesirable behavior as well as biosafety surveillance
      are needed.

PMID- 11998467
TI  - [Primary nursing: adapting a new working model at the surgical nursing service of
      the Clinics Hospital of Porto Alegre].
AB  - The present article reports the evolution of organizational models of health care
      in the hospital area, portraying part of this process at the Surgical Nursing
      Service of the Hospital de Clinicas de Porto Alegre. The different kinds of care
      are discussed on how they interfere on the Nursing duties. We approached Primary
      Nursing concepts and its repercussion in the nurse-patient relationship proposing
      alternatives to move our current work close to this trend.

PMID- 11998468
TI  - [Corporality in an orthopedics clinic scenario].
AB  - The study features the author's lived experience of phenomenological
      enlightenment in which she pursued to operate Polak's (1996) concepts of Nursing
      and Care, which have corporality as a reference. It describes the living
      experiences of four clients hospitalized in an Orthopedics and Trauma Unit of an
      School Hospital of Curitiba's metropolitan area, according to Polak's caring
      process moments, which are: perception; discovery and dialogue; building of new
      knowledge; and implementation of caring actions. It was noticed that the concepts
      are feasible on practical situations.

PMID- 11998469
TI  - [Gerontologic nursing: reflexion on the work process].
AB  - This article had the objective to reflect about Gerontology Nursing subsided on
      the work process approach, according to Marx. It is a bibliographical study in
      which Gerontology Nursing concepts, theoretical arguments, objectives and work
      process are verified. The results point out that it has as purpose to promote
      health, prevent diseases, give specific care, recovery and rehabilitation of the
      elderly, maintaining their functional capacity; as object the older human being
      and the aging process in itself; as instrumental the specific knowledge about the
      object, the instruments and the conducts directed to the elder; as product the
      elder taking care of him/herself and, under that impossibility, being suitable
      cared by his/her family in an humanistic way, keeping his/her dignity until
      death. From the reflections done, we applied the learned concepts about the
      Gerontology Nursing work process, trying to awaken to the importance of including
      Gerontology subjects while forming Nursing professionals.

PMID- 11998470
TI  - [Expectations, feelings, and experiences of the father during labor and the birth
      of his child].
AB  - This is a qualitative study, of the exploratory kind, that seeks knowledge about
      expectations, feelings and experiences of the father during the delivery and the
      birth of his child. The thematic content analysis according Bardin (1977)
      revealed the themes: "I expected I could be with her through the whole thing" and
      "A lot of emotions, you have to hold yourself...". The conclusion reached was
      that the father have the wish to be present in every moment related to delivery
      and birth of his baby.

PMID- 11998471
TI  - [Death versus feelings: a reality in the world of medical students].
AB  - The purpose of this investigation was to unveil the feelings of medical students
      while facing the phenomena of death, and also the meaning of these experiences on
      their lived-world and its implications to their academic training. The
      investigation was carried out with 10 students who are regularly registered in
      the Medical School of the Pontificia Universidade Catolica do Rio Grande do Sul
      (PUCRS), Porto Alegre, Brazil, attending between the 3rd and the 6th year. The
      qualitative approach, with phenomenological basis, along with theoretical
      assumptions of Merleau-Ponty and the information analysis method proposed by
      Giorgi (1988) and Comiotto (1992), disclosed five phenomenological essences: The
      meanings of death; Conflict between life and death; Feelings experienced on the
      interfaces of death; Medical training; Personal transformation as a path to
      professional transformation. The findings of this study evidence the feelings and
      their implications to the process of personal and professional development of the
      students as primordial and undeniable phenomenon. Considering this relevance, a
      psycho-pedagogical proposal is presented to educate feelings.

PMID- 11998472
TI  - [Perception and feelings of patients in the immediate postoperative period in
      heart surgery in relationship with the visit].
AB  - This research intends to know the perceptions and feelings of cardiac post
      surgical patients towards visitation, adjustment of visitation times and who's
      visit is the best. It is a qualitative study with a descriptive and exploratory
      character. Five adult patients were interviewed on the sixth day after surgery.
      To analyse the data we used Content Analysis as suggested by Bardin (1977). The
      results show that the patients consider the family as the main support for their
      condition. The time of visitation is enough for this critical moment and the
      family is also the ideal visitor. The difficulties to communicate with the
      visitor, however, are evident due to their physical and emotional conditions.

PMID- 11998473
TI  - [The purpose of nursing work with families dealing with mental disease in their
      daily lives].
AB  - The article reflects upon the purpose of the nursing work inserted in a
      particularly important historical moment to Mental Health System of the state of
      Rio Grande do Sul. It approaches the psychiatric assistance reform and in it the
      insertion of nurses and families that deal with mental illness, searching to
      define its purpose at the convergence between the essence of the proposal of the
      mental health assistance restructure and the daily lives of professional
      practice.

PMID- 11998474
TI  - [Intervention in the process of work-health-disease based on the Betty Neuman's
      systems model].
AB  - This article proposes a referential landmark directed to the worker's area,
      attempting to answer theoretical and methodological needs in this field of action
      and professional intervention. The controversy of the relation work-health
      disease and its implications to nursing are very challenging and, at the same
      time, quite intriguing as we seek for its interrelationships. Therefore, we
      intend to unfold them adopting the structural path of The Neuman Systems Model,
      systematizing a proposal of nursing action compromised with the relation work
      health-disease. Also, we wish to investigate stress factors at work, environment
      and individual resources to deal with them, and the goals established to the
      interaction between nurse and worker. This interaction is seen as fundamental to
      the proposal of educational and/or assistencial actions to the worker's health.
      It is our intention to contribute with information and propositions to induce
      reflective thought and debate about the subject.

PMID- 11998475
TI  - [Pesticide poisoning in rural areas and the nurse's work].
AB  - Organoclorines pesticides are compounds that were utilized in agriculture until
      1985, when their use was forbided, since they represented a risk for human health
      and environment. Nowadays, its clandestine use is still representative. These
      compounds may be used in public health campaigns to combat mosquitos that
      transmit malaria. If public health nurses know the particularities of these
      compounds, they will be able to work in health prevention and promotion,
      recognizing the chronic and acute damages as well as in the epidemiologic
      vigilance of the populations exposed. This paper presents a revision about the
      organoclorines pesticides and, based on it, proposes some activities to be
      implemented by nursing professionals in primary health care, aiming the health of
      workers exposed to the pesticides.

PMID- 11998476
TI  - [Biosafety: scientific production in nursing].
AB  - The aim of this study was to investigate thematic approach and methodological
      focuses used in researches about biosafety, as well as the qualification of the
      authors of papers published in Brazilian Nursing periodicals. The publications
      were classified according to the main subject, as follows: worker's health;
      patient's health; and environment. The results showed that in a 65 years period
      (1932-1997) a total of 224 studies about biosafety were published, 76 were
      articles and conferences; 148 scientific articles, monographs and thesis. There
      was a predominance of articles about worker's and patient's health. Most of the
      studies were descriptive researches and were published by nurses of the Southeast
      area of the country. The majority of the authors were teachers with a Master or
      Doctorate degree.

PMID- 11998477
TI  - [Characterization of children and adolescents with type 1 diabetes in therapeutic
      follow-up].
AB  - This descriptive study with mothers of children and adolescents carriers of
      diabetes type 1, aims to characterize these children and adolescents enrolled in
      elementary and high school, either public or private, while in therapy. To reach
      our purposes, we used direct interviews whose results led us to the following
      conclusions: most of them (83%) have been carriers of the disease for more than
      five years; 93.3% had been submitted to hospital treatment, considering
      hypoglycemia as the most frequent reason (46.7%). It also points toward the need
      to develop equity while caring for the family of children and adolescents with
      diabetes type 1, giving them support to cope with the child carrier of a chronic
      disease.

PMID- 11998478
TI  - When nurses participate in blood draws for DUI purposes.

PMID- 11998479
TI  - Was failure to get Clinitron Bed or turn Pt cause of decubitus ulcers? Case on
      point: Fisher v. North Hills Passavant Hospital, 2001 WL 864441 A.2d -PA.

PMID- 11998480
TI  - SC: prior injury and pre-existing injury dilemma: court affirms workers'
      compensation award.

PMID- 11998481
TI  - VA: nurse-expert allowed to testify in rape case: SANE nurse's testimony helps
      convict rapist.

PMID- 11998482
TI  - 'Following doctor's orders' is not a good defense for RN. Case on point: Meloy v.
      Bachmeier, 2001 WL 1160446 N.W.2d  -ND.

PMID- 11998483
TI  - Melee at mental hospital results in civil rights suit.

PMID- 11998484
TI  - 'Advice line' nursing is a tricky business. Case on point: Estate of Preston v.
      Permanente, 2001 WL 1382756 N.E.2d-OH.

PMID- 11998485
TI  - TX: did death result from methadone overdose?: Court finds failure to prove
      proximate cause.

PMID- 11998486
TI  - DC: former employee "zinged" on job reference: gratuitous comments trigger
      defamation suit.

PMID- 11998487
TI  - Nurse abused by therapist awarded $1.2 million. Case on point: McKay v. Ciani,
      2001 WL 1382666 N.E.2d-NY.

PMID- 11998488
TI  - The process of manuscript review and the improvement in publication quality.

PMID- 11998489
TI  - [The management work process: powerful tool for change in health care practice?].
AB  - This study analyzes how the management of healthcare services is articulated with
      the production organization in Basic Health Units by taking as a context the
      process of implementation of the SILOS technical care model. There is an attempt
      at operating with analytical instruments which enable the understanding of
      management work processes in their "micropolitical" aspects by correlating them
      to their "macropolitical" issues. It is concluded that the possibility of
      identifying areas of power in the management work exists, and they can produce
      transformation in healthcare services.

PMID- 11998490
TI  - [Analysis of scientific production of nurses from Minas Gerais published in
      nursing journals].
AB  - This is a descriptive, exploratory and retrospective study on the scientific
      production by nurses from Minas Gerais in BDENF Nursing journals from 1989 to
      1998. The main objective was to characterize the scientific production by nurses
      from Minas Gerais published in the national nursing journals which comprise the
      BDENF. The names of 5.613 nurses from the records of COREn/MG were included in
      the database in order to find authors and their writings. Fifty-four authors and
      87 writings were found with an average of 1.6 writings per author. The authors
      and co-authors who produce and publish are university professors working in
      collaboration with their peers.

PMID- 11998491
TI  - [An institutional evaluation design].
AB  - This study aims at describing the design used in the evaluation of technical
      nursing courses in Sao Paulo State's Education System by means of quantitative
      and qualitative institutional performance indicators. Such indicators,
      established by former students and by the labor market, showed to be useful in
      the evaluation and demonstrated the need for increasing, by means of similar
      evaluation studies, parameters related to the academic staff's performance as
      well as that of practical teaching fields. It is concluded that the use of a
      reasonable number of indicators allowed the articulation among data and a better
      understanding of the evaluated institutions.

PMID- 11998492
TI  - [Evaluation of the quality of the process of stoma demarcation and late
      complications in ostomized patients].
AB  - Following the characterization of adults with an intestinal stoma who were
      registered in the Program of Education and Support to Stomized Patients, the
      authors developed a descriptive study in order to evaluate the results of the
      process of intestinal stoma demarcation as well as to analyze late complications.
      The sample was formed by 50 subjects, 76% of whom had colostomies and 34% had
      ileostomies. Regarding the stoma location, 12% did not demonstrate the scientific
      specifications indicated for the distance from the waist line, 2% for the iliac
      crest and 2% for the surgery scar. Late complications appeared in 44% of the
      cases, such as: 28% of peristomal hernias, 16% of stoma prolapses and 4% of skin
      hyperemias.

PMID- 11998493
TI  - [The nursing process at a burns unit: an ethnographic study].
AB  - This ethnographic study aimed at understanding the cultural meaning that nursing
      professionals working at a Burns Unit attribute to the nursing process as well as
      at identifying the factors affecting the implementation of this methodology. Data
      were collected through participant observation and semi-structured interviews.
      The findings indicate that, to the nurses from the investigated unit, the nursing
      process seems to be identified as bureaucratic management. Some factors
      determining this perception are: the way in which the nursing process has been
      taught and interpreted, routine as a guideline for nursing activity, and
      knowledge and power in the life-world of the Burns Unit.

PMID- 11998494
TI  - [Reutilization of disposable syringes: frequency and costs for the administration
      of insulin at home].
AB  - The present survey has the purpose to analyze the frequency and costs of the re
      utilization of disposable syringes for insulin administration at home. One
      hundred and thirteen patients with diabetes assisted by a public hospital in a
      city in the interior Sao Paulo State, Brazil, were interviewed. The findings
      showed that regarding the studied population, the frequency of needles re
      utilization varied from 1 to 20 times, and syringes re-utilization from 1 to 60
      times. The greatest frequencies in the use of the same syringe or needle were of
      four times followed by three times. Re-utilizing the same syringe four times
      resulted in a cost reduction of 74.68%. The results pointed out the need for a
      legislation review as well as for new studies on the risks and benefits arising
      from this practice.

PMID- 11998495
TI  - [Ambulatory nursing care for patients with aortic valve disease].
AB  - This study aimed at characterizing the profile of outpatients with aortic valve
      dysfunction, identifying their knowledge about the disease, their major
      limitations during everyday activities and their means of coping with their
      predicament. The data obtained by semi-structured interviews with 12 patients and
      analyzed by quantitative and qualitative methods enabled to identify how the
      patients perceive the illness and the treatment as well as the implications to
      their everyday activities, that is, they allowed to capture reality from the
      subject's perspective, which is the knowledge for the elaboration of an
      educational proposal.

PMID- 11998496
TI  - [Building the meaning of disease recurrence: experience of women with breast
      cancer].
AB  - Regarding recurrence as a possibility in the lives of women with breast cancer,
      this work aimed at identifying how they construct the meaning of such possibility
      from their own existence. The study was based on the conceptions of symbolic
      interactionism and the content analysis of interviews with 12 mastectomized women
      was used. The possibility of recurrence was present in the lives of the women
      under study. It was configured by the uncertainty that they experienced and
      represented in the thematic units identified in their accounts when they stated
      to be "living with a stigmatizing disease", "experiencing a negative feeling" and
      "facing prejudice".

PMID- 11998497
TI  - Issues in the application of research to practice.
AB  - In recent years calls for evidence-based practice are being made emphatically in
      the nursing literature worldwide. Yet, the underlying construct, which relates to
      use of scientifically-based knowledge and research to practice, has been with us
      for a long time. This analytic paper provides an overview of research utilization
      models developed and used in nursing and other fields, highlighting some of their
      features. The paper then reviews research utilization and application issues at
      the institutional level, highlighting the importance of organizational mechanisms
      for enabling optimum research use and application, rather than relying on
      individual nurses. It then describes ways in which research can be used at the
      societal level in the formation of healthy public policies, using the United
      States as a case study. A number of recommendations are then presented for
      organizations and the profession at large in a global context.

PMID- 11998498
TI  - [Breastfeeding and nutrition beliefs].
AB  - Hypogalactia has been one of the reasons that lead mothers to early weaning.
      Beliefs and taboos influence breastfeeding during lactation. This study aims at
      identifying regional lactagogues used as a support to breastfeeding based on
      taboos and beliefs. It is a case report which uses prose analysis. The findings
      show that feeding oneself with certain types of food or not, having experienced
      breastfeeding, beliefs transmitted by family members and physicians and the
      child's growth and development were factors which stimulated breastfeeding.

PMID- 11998499
TI  - [The nurse's work in mental health services of the public network of Campinas
      SP].
AB  - This work aimed at verifying the field of performance of nurses in the mental
      health services in the city of Campinas-SP as well as at analyzing their work
      relations with other members of the multi-professional staff as an attempt to
      observe the nexuses established between such professionals' practice and the
      service's conception concerning team work. A qualitative and descriptive
      investigation was conducted which used the case report as a research methodology.
      It was observed that nurses take different roles according to the organization of
      the team's work process and that the recognition of such context is essential for
      nursing professionals to develop their work critically and to keep high quality
      standards.

PMID- 11998500
TI  - [Bibliographic study of publishing on management activity of nursing in mental
      health].
AB  - Aiming at studying the mental health nurse's management activity as an instrument
      in the work process, a bibliographic study on nursing publications from 1988 to
      1997 which concerned that topic was carried out. By reading and critically
      analyzing 8 articles and 19 selected theses and dissertations, the major
      characteristics of such practice were identified, namely: mental health nurses
      are responsible for the nursing team and care according to the logic determined
      by the institution; their actions are not planned, coordinated or evaluated;
      management activities take most of their time and direct nursing care is given by
      the auxiliary nursing team whilst in extra-hospital services, direct and group
      care are more frequent.

PMID- 11998501
TI  - [Iatrogenic episodes at the ICU and the quality approach].
AB  - Regarding iatrogenic occurrences in ICUs as events that interfere with the
      quality of the care given to critical patients, the author contextualizes such
      occurrences by taking into account the principles of Total Quality Management as
      a theoretical framework.

PMID- 11998502
TI  - [Participation of occupational nursing in the work program of hearing
      protection].
AB  - This text aims at pointing out the importance of the occupational nurse's
      participation in the Hearing Conservation Program for workers exposed to high
      levels of noise through actions based on the Nursing Process with the purpose to
      enlarge the knowledge in this specialty and nurses' effective role in the
      multidisciplinary team for workers' care.

PMID- 11998503
TI  - Eating our young.

PMID- 11998504
TI  - Managing advanced prostate cancer with Viadur (leuprolide acetate implant).
AB  - Viadur (leuprolide acetate implant), providing a sustained release of drug over a
      12-month duration, decreases serum testosterone in advanced prostate cancer
      patients, providing long-term, palliative medical hormonal therapy. Clinical
      experience suggests Viadur implants are safe, effective, and generally well
      tolerated. The continuous drug delivery provided by Viadur ensures compliance.
      The Viadur implants was designed to be maintenance-free, thereby allowing nurses
      and other health professionals to focus on other patient needs, such as followup
      visits and diagnostic tests. Viadur is one aspect of a comprehensive approach to
      patient management, which also includes regular followup for prostate-specific
      antigen testing, digital rectal examination, and other tests throughout the 1
      year therapy.

PMID- 11998505
TI  - Depressive symptoms in women with urinary incontinence: a prospective study.
AB  - In this prospective study, the incidence of depression in women who suffer from
      urinary incontinence (UI) is examined. Although the literature has confounding
      information directly linking depression to UI, this study revealed depression was
      significantly higher in women with UI as opposed to their counterparts without
      UI.

PMID- 11998506
TI  - Biofeedback and electrical stimulation therapy for treating urinary incontinence
      and voiding dysfunction: one center's experience.
AB  - Urinary incontinence affects 13 million Americans at a cost of $11.2 billion
      annually to the community. With an aging population, these numbers are expected
      to increase substantially in coming years. At the Bladder Control Center in
      Cincinnati, staff have completed over 3,600 biofeedback sessions with encouraging
      results.

PMID- 11998507
TI  - Impact of commercial marketing on patient demand.
AB  - This pilot study attempts to determine the impact of commercial direct-to
      consumer advertising on the incidence of patients requesting medication for
      urinary incontinence by brand name. Of 310 patients interviewed prior to
      urodynamics, 237 (76%) sought treatment after seeing related commercials. After
      testing, 119 (50.2%) were prescribed the advertised drug for detrusor
      instability. Fifty-nine (24.8%) were diagnosed with intrinsic sphincter
      deficiency and were recommended anticholinergics, collagen injections, or
      surgery. Forty-one (17.2%) men were found to have bladder outlet obstruction, but
      only four were prescribed the advertised drug. Three (1.2%) were recommended
      intermittent catheterization along with the advertised drug and 15 (6.6%) had
      various other treatments. The results suggest that 50% of those seeking treatment
      were not candidates for the medication advertised.

PMID- 11998508
TI  - Soy extract reduces prostate cancer growth in mice, cell culture.

PMID- 11998509
TI  - Another hormone receptor may be involved in development and growth of prostate
      cancer.

PMID- 11998510
TI  - Market research on urinary incontinence offers insightful findings.

PMID- 11998511
TI  - Study shows patients taking vardenafil consistently completed sexual intercourse.

PMID- 11998512
TI  - Getting ready for certification: urinary tract inflammations and disorders.

PMID- 11998513
TI  - [Why does a mastoidectomy cavity become suppurative? Our experience and revision
      of the literature].
AB  - The main goal for performing surgery for chronic otitis media is to eliminate the
      disease and improve hearing whenever possible. Persistent drainage of a mastoid
      cavity means failure of surgery and of achieving the goal. In this study, we
      present our department's attitude for suppurative mastoid cavities as well as the
      reasons that do not allow adequate control of them.

PMID- 11998514
TI  - [Tonsillectomy by electrical dissection: risk factors of postoperative hemorrhage
      in children].
AB  - OBJECTIVE: To identify pre or intraoperative risk factors that could indicate a
      higher risk for post-tonsillectomy hemorrhage (PTH) in children undergoing
      electrocautery dissection. SET-UP: Primary referral hospital. DESIGN: A
      retrospective study of 163 post-tonsillectomy children comparing 7 cases of PTH
      with 156 cases with no PTH. SAMPLE: This study includes children under the age of
      18 that underwent tonsillectomy by dissection between 1997 and 2000. OUTCOME
      PARAMETERS: Age, sex, height, weight, body mass index, hemoglobin level,
      hematocrit, platelet count activated partial thromboplastin time (APTT),
      fibrinogen, ASA index (physical state classification of the American Society of
      Anesthesiology) and type of hemostasis. RESULTS: Prevalence of PTH was 4.29% in
      the cohort sample. The risk of PTH in children following tonsillectomy by
      electrodissection is significantly increased in patients over 15 years of age (OR
      = 8.46, p = 0.04) and when ligatures are used for hemostasis (OR = 8.62, p =
      0.02). Activated partial thromboplastin time > or = 32 seconds is marginally
      significant (OR = 7.82, p = 0.05). CONCLUSIONS: Our findings show that
      tonsillectomy by electrodissection has an increased risk of bleeding in older
      children and when ligatures are used for hemostasis.

PMID- 11998515
TI  - [Results of using botulism toxin in the treatment of spasmodic dysphonia].
AB  - Spasmodic Dysphonia (SD) is a dystonia involving laryngeal musculature thus
      causing a characteristic voice disorder. Two main types of SD have been
      described. The adductor type is the commonest and it is characterized by a strain
      strangle, choked voice. The abductor type can be distinguished from the previous
      one by episodes of a blown and whispering voice, interrupting speech. Botulism
      toxin (BTX) has demonstrated to be the most effective treatment for this
      condition. Thirty patients diagnosed of SD (twenty-nine adductor type/one
      abductor type) were included. Their degree of dysphonia was evaluated using both
      functional and visual-analogue scales. They were treated with BTX vocal cord
      injections using a percutaneous technique under EMG guidance. Improvements up to
      a 100% of the normal vocal function were obtained, with an average of 82% in the
      adductor type. The adverse effects were mild and transient. Hypophonia affected
      61.3% of patients lasting an average of 11.3 days. Dysphagia was reported in
      44.1% of cases lasting an average of 5.8 days.

PMID- 11998516
TI  - [Factors affecting local and regional control and survival of carcinomas of the
      tongue and floor of mouth].
AB  - A retrospective study of 142 patients that had previous surgery for carcinoma of
      the tongue or floor of mouth looking into the factors that affect significantly
      the evolution of our patients and in which circumstances we could benefit from
      new therapeutic techniques. Cause specific survival at 3 and 5 years was 63.4%
      and 56.9% respectively. Recurrences were found locally in 32 patients (22.5%),
      regional in 32 (22.5%) and metastasis in 11 (7.4%). T staging had no did impact
      on local recurrence, but the presence of positive margins (p = 0.0323). Regional
      control for N0/N1 was 85% (90/106) versus 55.5% (20/36) for N2/N3 (p = 0.001).
      Regional control by N staging was 84.5% (73/86) for N0, 85% (17/20) for N1, 57%
      (30/35) for N2 and 0% for N3 (0/1). Both, N staging and number of positive nodes
      had a significant impact in specific survival. Positive margins and the presence
      of positive nodes have the greatest impact on survival and regional control.
      Adjuvant postoperative radiotherapy did not increase survival, but not
      prospective random selection was performed. To evaluate this.

PMID- 11998517
TI  - [Pedicled pectoralis major musculocutaneous flaps].
AB  - A retrospective series of 76 pedicled pectoralis major musculocutaneus flaps is
      presented. We used this technique in reconstruction after head and neck tumours
      resections and in complications of oncological surgery such as pharyngostomes or
      orostomes. Most of these flaps were used in reconstruction of oral cavity and in
      postradiotherapy salvaje surgery cases. We also analyse the presence of
      complications at the donor and receiver sites and its correlation with different
      parameters like protein levels, haemoglobin, administration of radiotherapy and
      its dose, previous quimiotherapy and the influence of systemic diseases.

PMID- 11998518
TI  - [Mucocele from concha bullosa with invasion of the orbit].
AB  - We present a case of a 44-year-old man that came to the clinic with exophthalmus
      and frontal headaches. TC and MRI showed a fronto-sphenoidal mass with extension
      to the cribiform plate involving the orbit and pushing the eyeball forward. The
      mass was completely excised through intranasal endoscopic surgery and it was
      found out to be a mucocele from concha bullosa.

PMID- 11998519
TI  - [Evaluation of the morphology of stapedial reflex in otosclerosis. Provoked
      otosclerotic stapedial reflex].
AB  - Stapedial reflex is used, amongst other pathologies, for the study of
      otosclerosis. In this retrospective study we have collected 188 cases of patients
      with otosclerosis whose diagnosis has been confirmed surgically and their first
      line relatives. We have performed a descriptive analysis of audiometric tests,
      tympanometries and ipsilateral stapedial reflexes in relation with the evolutive
      phase of the disease. Transmission hypoacusis has been seen in 54%, mixed
      hypoacusis in 29% and sensorineural hypoacusis 8% of cases. On and OFF stapedial
      reflexes have been seen in 18%, inverted reflexes in 46% and absent reflexes in
      27% of cases. The original drawings of the different types of reflexes during the
      evolution of otosclerosis can be seen in the four figures shown in the study:
      normal reflexes; ON and OFF a, b and c types; inverted a and b; and absent
      reflexes. The clinical evolutive phase and the audiometric and impedance tests
      have been correlated. Through Chi-square (p < 0.001), we have obtained a
      statistical significance in relation to the use of stapedial reflexes. Also it
      has been suggested the use of provoked stapedial reflexes in patients with sub
      clinical otosclerosis in order to diagnose the disease. We conclude that the
      knowledge of the evolutive morphology os stapedial reflexes in otosclerosis helps
      diagnostic capacity.

PMID- 11998520
TI  - [Pharyngeal branchial cyst: description of one clinical case].
AB  - Brachial cysts are abnormalities in the development of the branchial apparatus,
      being the more common ones those of the second arch. Cysts localized in the
      pharyngeal wall (Bailey's type IV) are extremely rare; therefore its differential
      diagnosis should include all benign and malignant lesions that can be found in
      the pharyngeal wall. Treatment is the total excision of the cyst through per oral
      or external cervical approach in order to avoid recurrences.

PMID- 11998521
TI  - [Intra-laryngeal ectopic thyroid tissue. Report of one case and review of the
      literature].
AB  - A Ectopic thyroid is any thyroid tissue not located in his normal anatomic
      situation. There have been described four general groups within the upper
      aerodigestive tract: lingual, sublingual, thyroglossal and intralaryngotracheal.
      Intralaryngotracheal thyroid tissue is rare and constitute 7 per cent of all
      intratracheal tumours, and it represents a problem of diagnosis and management.
      The controversy about the genesis of this tumours remains. There are two
      established theories: "the malformation theory" and "the ingrowth theory". These
      tumours affect more frequently adult female. Intralaryngotracheal thyroid have
      been mainly reported on the posterior-left wall of the trachea. The most common
      clinical feature is stridor due to progressive upper airway obstruction. Up to
      75% of the intralaryngotracheal goiters are associated with and external goiter.
      This paper reports a case of ectopic subglotic thyroid in a 42 year-old-female.
      The embryology, diagnosis and management of this tumours are discussed.

PMID- 11998522
TI  - [Liposarcoma of the hypopharynx].
AB  - Liposarcomas (LS) of the hypopharynx are uncommon tumors. All the literature
      considers laryngeal and hypopharyngeal liposarcomas together, and they represent
      10-15% of all LS of the head and neck. Obstruction of the upper respiratory tract
      and dysphagia are usually the initial symptoms. The histological subtype is the
      most important prognostic factor. Surgery is the treatment of choice. Recurrences
      are frequent. We present a case about a liposarcoma in a 81 years-old man.
      Diagnosis, evolution and treatment are evaluated.

PMID- 11998523
TI  - [Metastasis in submandibular gland from a leiomyosarcoma of the uterus].
AB  - Two general types of metastases should be distinguished in metastatic salivary
      gland tumors: one of them are tumors originating in the head and neck region, and
      the other are tumors from distant tumor sites. Distant metastasis affecting the
      submandibular gland are a rare entity. We report a case of the uterus
      leiomyosarcoma which metastatised in the submandibular gland.

PMID- 11998524
TI  - [Nasal polyposis: postoperative long term results (5 years) after endoscopic
      sinus surgery].
AB  - The purpose of this study is to evaluate the results after endoscopic sinus
      surgery in cases of nasal polyposis. We include 54 patients with diffuse nasal
      polyposis suffering from nasal obstruction. An endoscopic sinus surgery under
      general anesthesia with excision of the polyposis was performed. There were no
      complications. The patients were followed closely and treated with local and
      systemic steroids. After 5 years, the 75% of these patients were free of nasal
      symptoms and in the 67% the mucosa appeared normal. We also review the influence
      of some factors (ASA triad, anosmia, allergy...) in the recurrence of the
      disease.

PMID- 11998525
TI  - [Multi-level treatment for obstructive sleep apnea syndrome: comparative study of
      four different surgical techniques of palate].
AB  - Palatopharyngeal surgery is a therapeutic option for Obstructive Sleep Apnea
      Syndrome. This surgery is based on the assumption that the soft palate is the
      principal apneogenic area of the upper airway. We report a comparison of four
      techniques of palatopharyneal surgery. In the other hand, the effectiveness of
      palatopharyngeal surgery for correcting other obstructions when present, was also
      evaluated.

PMID- 11998526
TI  - [Atypical Cogan's syndrome: report of two cases and revision of literature].
AB  - Cogan's syndrome is a rare autoimmune disease with systemic involvement. It
      appears in young people and has two presentations: the typical form with
      keratitis, sudden deafness with or without vestibular syndrome, and the atypical
      form with different non keratitic ocular diseases and a great variety of systemic
      symptoms in relation with the autoimmune etiology of the process. Cogan's
      syndrome has a bad prognosis and deafness appears in 25% of the cases with the
      right treatment and in 60% of patients without treatment. The best treatment is
      systemic and ocular corticotherapy. The second treatment of choice is
      cyclophosphamide or cyclosporine A. We present two cases of atypical Cogan's
      syndrome with unilateral deafness in both.

PMID- 11998527
TI  - [Midfacial necrosis secondary to cocaine-abuse].
AB  - Midfacial necrosis due to the abuse of inhaled cocaine is a new entity that is
      included in the differential diagnosis of the midline destructive diseases such
      as Wegener's granulomatosis, polymorphic reticulosis, nasal lymphoma, infections
      and the idiopathic midline destructive disease. We report the case of a forty
      year-old male who presented necrosis of the nasosinusal tract and optic
      neuropathy as complications due to the abuse of inhaled cocaine for more than
      twenty years and a discussion about the differential diagnosis.

PMID- 11998528
TI  - [Inflammatory pseudotumor of paranasal sinuses].
AB  - Inflammatory pseudotumor is a rare benign lesion of unknown etiology which was
      first described in the lung. In head and neck the areas most commonly involved
      are the orbit and paranasal sinuses, but they have been also described in the
      larynx, pterygomaxilar space, tonsils, ears, gingiva and other periodontal
      tissues. We present a case of a 64 years old male who presented a three months
      history of right nasal obstruction. Physical examination showed a big nasal tumor
      arising from the nostril. CT scan shows nasal fossa mass with a normal paranasal
      sinuses. Histology made the diagnosis of an inflammatory pseudotumor. The lesion
      was surgically removed trough a midface degloving approach. The patient has no
      signs of recurrence two years after surgery. Data about diagnosis, treatment and
      outcome of inflammatory pseudotumors is revised also in this paper.

PMID- 11998529
TI  - [Cervical metastasis from testicular teratoma].
AB  - The presence of neck metastasis in patients with testicular germ cell neoplasms
      in a rare but well known phenomenon. The incidence of neck metastasis in
      testicular carcinoma has been reported to be present in a 5% of cases. When
      cervical metastasis occurs, surgical resection of the residual disease following
      chemotherapy and using a specific technique of modified neck dissection results
      in a surprisingly improvement of the prognosis.

PMID- 11998530
TI  - [Diphtheria and Renaissance Spanish physicians].
AB  - Along the history of medicine, diphtheria has been the cause of many deadly
      epidemics. Up to the incorporation of microbiology in medicine and the definition
      of diphtheria provided by Bretonneau in 1826, this disease was studied with all
      types of sore throut into the galenic system. Spanish physicians in Renaissance
      started the way to its systematisation, taking it off the rest of sore throat
      types, with other laryngeal diseases, as it was known later as "croup", giving it
      the name of "garrotillo". They were the first to describe some important
      questions about this disease, as the specificity of the diphtheric
      pseudomembranes, the ineffective potential of salivary drops and the palsy of the
      soft palate.

PMID- 11998531
TI  - [Contribution to the development of the union between the manubrium of the
      malleus and the tympanic membrane in human fetus].
AB  - The development of the union between the manubrium of the malleus and the
      tympanic membrane was studied in human embryo. For that purpose 25 temporal bones
      of human foetus, aged from 36 days (14 mm) to 29 weeks (270 mm) were analyzed.
      Samples were fixed in a 10% formaldehyde solution, decalcified with 2% nitric
      acid, embedded in Paraplast, cut in sections of 7 microns thick and stained with
      Martin's trichrome method. During the development a pseudojoint between the
      malleus and the tympanic membrane several stages were seen. In the first stage,
      the manubrium was adhered to membrane mesenchyme of primitive tympanum, in the
      second one this mesenchyme was loose and there appeared capillars in it, in the
      third one there were collagen fibers in a radial disposition, and in the forth
      stage, the hollow in the meatal plug gave independence to the tympanic membrane
      for the external acoustic meatus. The distal portion of the manubrium, included
      in tympanic membrane, has remained with a cartilaginous structure during end of
      the time it has been studied by us. The collagen fibers at the level of the umbo
      surround the manubrium, while the rest of it remains in its anterior edge.

PMID- 11998532
TI  - [Computerized analysis of craniography: new limits of the norm for static and
      dynamic forms].
AB  - Literature about normal parameters of Craniocorpography (CCG) is scant and poorly
      documented. Its results are variable according to the series. Our aim is to reach
      a criteria of normality for CCG in our reference population. We have
      prospectively made Romberg and Unterberger tests to 72 healthy volunteers (mean
      age 34.7 years old, SD 17.07, 55.6% men) using a computerized method of
      measurement and making its estimation by means of a statistical model widely
      accepted. All the studied variables observe the conditions of Gaussian
      distribution. The normal limits for lateral and antero-posterior oscillation were
      9 centimeters, 12 centimeters for lateral sway and 59 degrees to the right and 46
      degrees to the left for angular deviation. The computerized method of analysis
      has facilitated the detection of the limits of the light tracings, which together
      with the careful design of our study guarantees the validity of the results.

PMID- 11998533
TI  - [Trans-labyrinthine approach for the resection large and giant acoustic nerve
      neuromas].
AB  - The standard translabyrinthine approach for acoustic neuromas removal was
      introduced by W. House in 1964. After several years of experience the original
      translabyrinthine approach has been progressively modified into the current
      "enlarged" approach by extending the area of bone removal. This increased
      surgical field has made the translabyrinthine approach suitable for the removal
      of tumours of all sizes. We present our serie of 71 large (52) and giant (19)
      neuromas of the VIIIth nerve removed through a translabyrinthine approach between
      1993 and 1998 at the ENT Department of Legnano.

PMID- 11998534
TI  - Fate of abstracts presented at five International Conferences on
      Pharmacoepidemiology (ICPE): 1995-1999.
AB  - BACKGROUND: Meetings are an important way of exchanging scientific information,
      but full diffusion of new information can only be achieved when results are
      published in scientific journals. PURPOSE: (1) To determine the publication
      frequency of accepted abstracts for the yearly international conferences on
      pharmacoepidemiology (ICPE) and to examine predicting variables; (2) if
      published, to determine impact differences between 'oral' and 'poster' abstracts
      and to determine type and nature of publishing journals. METHODS: Abstracts
      accepted for ICPE 1995-1999, published in the official conference supplement of
      Pharmacoepidemiology and Drug Safety, were included. Publication status for the
      information contained in each abstract was evaluated through MEDLINE and IPA
      searches. Impact factors of publishing journals were retrieved and journals were
      included in one of five groups. RESULTS: Overall, one out of three abstracts
      resulted in a publication in the peer-reviewed journals studied. Abstracts from
      North America were more often presented orally than abstracts from Europe, but
      had lower publication chances. 'Oral' abstracts were more likely to be published
      than 'poster' abstracts; abstracts with a strong methodological content had a
      lower publication frequency. Most of the published abstracts were found in
      pharmacology and pharmacy journals (33%) and journals on specific clinical topics
      (30%). CONCLUSIONS: Only one out of three papers presented at ICPE ends up in
      established peer-reviewed journals. Although the publication characteristics for
      ICPE are not very different from other conferences, there are certain questions
      that warrant further investigation.

PMID- 11998535
TI  - Parenteral ketorolac and risk of myocardial infarction.
AB  - PURPOSE: To examine the effects of ketorolac, a non-aspirin non-steroidal anti
      inflammatory drug (NANSAID) with antiplatelet properties, on the risk of in
      hospital myocardial infarction (MI). METHODS: A retrospective cohort study was
      performed among hospitalized patients given 10,219 courses of parenteral
      ketorolac and patients given 10,145 courses of parenteral opioids, without
      ketorolac, in 35 hospitals. Patients were matched by hospital, admitting service,
      and date of study drug initiation. Any MI documented in the chart that occurred
      during the drug course and up to 3 days after the last dose was recorded by
      trained abstractors. RESULTS: MI occurred in 18 (0.2%) ketorolac and 45 (0.4%)
      opioid courses (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.23-0.69).
      This negative association persisted in multivariable analysis adjusting for age,
      sex, history of diabetes mellitus or cardiovascular disease, and administration
      of antiplatelet agents (OR 0.42; 95% CI 0.24-0.73). The association also
      persisted in numerous analyses excluding patients who may have been treated with
      analgesics for ischemic pain, and when restricting events to those occurring
      while on the drug (OR 0.34; 95% CI 0.17-0.69). CONCLUSION: These results are
      consistent with a protective effect of ketorolac against MI. Future research that
      implements uniform screening for and independent validation of MIs as well as
      eliminates possible confounding by indication is the next logical step in
      confirming these findings.

PMID- 11998536
TI  - Automated support for pharmacovigilance: a proposed system.
AB  - Governments, manufacturers, and other entities are interested in adverse event
      surveillance of marketed medical products. FDA's Center for Drug Evaluation and
      Research redesigned the post-marketing adverse reaction surveillance process to
      use the advantages of new technology. As part of this effort, a
      'Pharmacovigilance Working Group' designed a new strategy for the review and
      analyses of adverse event reports received by FDA. It created requirements which
      divided signal detection into five tiers: (1) Single 'urgent' reports would be
      sent to reviewers' workstations nightly for immediate attention. Reviewers would
      be able to customize definitions of 'urgent' (events that should not wait for
      aggregate review). (2) Single urgent reports would be placed in a context matrix
      containing historical counts of similar events to aid in initial interpretation.
      (3) In this first level of aggregate review, graphical displays would highlight
      patterns within all the reports, both urgent and non-urgent, and (4) periodic
      drug-specific tabled-based reports would display the newly received reports
      across a pre-defined variety of displays. These four tiers would produce passive
      and criteria-based results which would be presented to safety reviewers'
      electronic workstations. (5) Active query capabilities (routine, such as age,
      sex, and year distributions, as well as ad hoc) would be available for exploring
      alerted issues. The historical database would be migrated into the new format.
      All historical and new reaction data would be coded with the new MedDRA (Medical
      Dictionary for Regulatory Activities) scheme. The strategy was to design a full
      data capture system which effectively exploits current computing advances and
      technical performance to automate many aspects of initial adverse event review,
      supporting more efficient and effective clinical assessment of safety signals.

PMID- 11998537
TI  - Inappropriate prescriptions for the aging population of the United States: an
      analysis of the National Ambulatory Medical Care Survey, 1997.
AB  - PURPOSE: Generally, elderly patients in the United States tend to consume more
      prescriptions than younger adults. The purpose of the study is to examine
      nationwide prescription patterns for elderly patients who visited physicians'
      offices in 1997. METHODS: The database of a nationwide sample survey of
      practicing physicians participating in the National Ambulatory Medical Care
      Survey, 1997 was used. Inappropriate medicines for the elderly were identified
      using previously published and widely accepted criteria. RESULTS: During 1997,
      patients aged 65 years or older made more than 191 million visits to physicians'
      offices in the United States. Four or more prescriptions per visit were issued
      with the following frequencies: 17.7% for females; 16.4% for males; 17.0% for
      Whites, 22.7% for Blacks, and 6.1% for other minorities including American
      Asians, Indians, Eskimos, Aleuts and Pacific Islanders. The frequencies with
      which at least one inappropriate medication per visit was prescribed were: 10.8%
      for females; 8.9% for males; 10.3% for Whites; 9.7% for Blacks; and 1.9% for
      other minorities. DISCUSSION: Four or more prescriptions issued per visit and
      inappropriate prescriptions for the elderly in the United States were evident,
      and may put a vulnerable aging population at risk of adverse drug events.

PMID- 11998538
TI  - Variability in abciximab (ReoPro) prescribing: evidence based or budget driven?
AB  - PURPOSE: Abciximab improves outcomes in patients undergoing percutaneous
      transluminal coronary intervention (PTCA). Clinicians, however, have expressed
      concerns that they do not have enough budget to administer abciximab to all
      eligible patients. We studied the patterns of prescribing of abciximab and
      identified factors that correlate with the level of usage. METHODS: In each of
      all 13 Dutch PTCA centres one opinion-leading cardiologist was approached to
      provide data on the abciximab prescribing in their centre and to co-operate in an
      interview on this topic. We performed linear regression analysis in which the
      level of abciximab prescribing was the dependent variable. Potential determinants
      investigated were the number of PTCAs performed, the criteria for abciximab
      prescribing, funding and possible financial restrictions, participation in
      clinical trials in the past, percentage stenting, and desired level of abciximab
      prescribing. RESULTS: All 13 PTCA centres in the Netherlands participated in our
      study. The level of abciximab prescribing varied from 2 to 36% of all PTCAs. The
      criteria for patient selection significantly differed between centres. Together
      budget, investigatorship, size, and type of the institution were highly
      predictive for the level of abciximab prescribing (R2 = 0.93, p < 0.001). The
      more patients doctors had included in clinical trials in the past, the higher was
      the likelihood that they had prescribed abciximab. CONCLUSIONS: Shortly after its
      introduction, patterns of abciximab prescribing varied widely between PTCA
      centres. There was no agreement on which patients to select for this preventive
      treatment. Budget and involvement in clinical trials in the past were important
      predictors of the level of prescribing in each centre.

PMID- 11998539
TI  - Results of a postal survey of the reasons for non-response by doctors in a
      Prescription Event Monitoring study of drug safety.
AB  - PURPOSE: A Prescription Event Monitoring (PEM) study was carried out by the Drug
      Safety Research Unit (DSRU) to monitor the safety of irbesartan, an angiotensin
      II antagonist, immediately after launch in the United Kingdom in September 1997.
      The DSRU 'green form' questionnaire response rate was lower than expected. The
      manufacturer was conducting a concurrent postmarketing surveillance study. The
      aim of this cross-sectional study, was to identify reasons for non-response by
      general practitioners in England. METHODS: In PEM, questionnaires are posted to
      the prescribing general practitioner approximately 6 months after the date of the
      first prescription for each patient, requesting details of clinical events
      recorded in the patients' notes since starting treatment. Those that failed to
      respond were sent a second questionnaire, including tick box questions to
      elucidate reasons for non-response. RESULTS: A total of 21.3% (3088/14502) second
      send forms were returned. There were 1747 tick box responses. The most common
      reason specified for non-response was 'I was too busy' (31.2%) followed by 'no
      payment included' (13.4%). Participation in another study accounted for only
      3.4%. CONCLUSIONS: The concurrent postmarketing surveillance study was not a
      significant factor. The general practitioner's workload appeared to have a far
      larger impact. While research remains a non-core activity and receives no
      payment, participation is likely to fall. Researchers need to find means of
      benefiting the general practitioner if participation is to continue.

PMID- 11998540
TI  - Drug prescribing patterns in Parkinson's disease: a pharmacoepidemiological
      survey in a cohort of ambulatory patients.
AB  - PURPOSE: Drug treatment of idiopathic Parkinson's disease (IPD) is a difficult
      task, and comorbidity and comedication add to its complexity. Since in IPD there
      is little information about drug use, this study investigated drug prescribing
      and indications in IPD patients. METHODS: From June 1997 to April 1998, a cross
      sectional survey of IPD outpatients was performed and demographic and clinical
      data and information about drug treatments was collected and analysed. RESULTS:
      In the 130 IPD patients included in the study, anti-Parkinson drug (APD)
      prescriptions increased with disease duration and severity. Levodopa was most
      frequently used, followed by dopamine agonists and anticholinergic agents.
      Levodopa with other APDs was given to older patients with later IPD onset.
      Prescriptions of drugs for other indications (non-APDs) were given to 80.8% of
      the patients and their number increased with patient age. Non-APD prescriptions
      concerned mainly the circulatory system, mental disorders, the musculoskeletal
      system and the digestive system. Prescriptions for indications corresponding to
      secondary symptoms that often complicate IPD increased with patient age and also
      with IPD duration. CONCLUSION: In IPD patients, disease duration and severity and
      patient age seem to be major determinants of drug use. Indications for drug
      prescription suggest that main comorbidity includes neuropsychiatric,
      circulatory, musculoskeletal and digestive disorders. Analysis of prescribing
      patterns in IPD can provide a readily accessible indirect indicator of patient
      health status for both health services and epidemiologic research purposes.

PMID- 11998541
TI  - Classification of ADRs: a proposal for harmonization and differentiation based on
      the experience of the Comprehensive Hospital Drug Monitoring Bern/St. Gallen,
      1974-1993.
AB  - The present paper deals with the classification of adverse drug reactions (ADRs)
      according to today's largely accepted pathomechanisms. The classification system
      applied, relies primarily on the proposals of Rawlins and Thomson with type A
      ('augmented') and B ('bizarre') reactions. In the database of the Comprehensive
      Hospital Drug Monitoring (CHDM) Bern/St. Gallen on 48,005 consecutively
      hospitalized patients, ADRs had been attributed to 10 different pathomechanisms.
      These permit a versatile new system, easily adaptable to expanding knowledge. If
      we look at the 12,785 ADRs registered in the CHDM Bern/St. Gallen from 1974 to
      1993, 76% were of type A, 13% of type B, and 11% of a pathomechanism not yet
      defined (type X). The main subgroups were A1 'not specified' in type A, Ba
      allergic/immunological and Bpa pseudoallergic/anaphylactoid in type B. Dose
      related (A2) and drug-related reactions (A4, intolerance in a restricted sense),
      drug-to-drug interactions (A5), rebound/withdrawal effects (A6) and secondary
      reactions (A7) represented smaller subgroups. Patient-related reactions (A3,
      'idiosyncrasy' in the strict sense) were not assessed. Today's algorithms for
      ADRs mainly rely on pharmacological, i.e. type A reactions. For most of the type
      B reactions adaptations including the experience of allergists, clinical
      immunologists and infectious disease specialists should be respected.

PMID- 11998542
TI  - Modeling methods for facilitating decisions in pharmaceutical policy and
      population therapeutics.

PMID- 11998543
TI  - Comment on 'Medication use and risk of falls' by Neutel et al.

PMID- 11998544
TI  - Medication use and risk of falls.
AB  - PURPOSE: Injuries due to falls are an important public health concern,
      particularly for the elderly, and effective prevention is an ongoing endeavour.
      The present study has two related objectives: (1) to describe associations
      between drug use and falls in an institutionalized population, and (2) to
      identify a high risk subgroup within the larger population. METHODS: The initial
      analysis was based on a population of 227 residents who were followed over a 1
      year period. Logistic regression techniques were used to estimate odds ratios
      (ORs) of the association of falls and drug use. The study of potential 'high
      risk' groups employed a case-crossover design to estimate the risk of falling
      associated with starting a new drug course. RESULTS: Relatively weak ORs for risk
      of falling were observed for various drug classes; the highest OR was for
      benzodiazepines (BZD) at OR = 1.8 (unadjusted). Residents taking multiple drugs
      were at particular risk for falling, e.g. an OR of 6.1 for those using 10+ drugs.
      The case-crossover analysis indicated that residents starting a new
      BZD/antipsychotic were at very high risk (OR = 11.4) for experiencing a fall.
      CONCLUSIONS: Residents who took many different types of medications, as well as
      residents starting a new BZD/antipsychotics were at greatly increased risk of
      falling. These are high risk groups where increased monitoring or adjustments to
      drug regimens could lead to prevention of falls.

PMID- 11998545
TI  - Should cases with a 'known' cause of their disease be excluded from study?
      (commentary).
AB  - Assigning a cause to an individual event is a natural impulse. This impulse
      sometimes finds its way into epidemiologic research, if researchers assign a
      specific cause to some cases of a disease under study. In epidemiologic studies
      of drug effects, assigning a cause to specific cases is often used as a reason to
      exclude these cases from cohort or case-control studies, because the disease in
      these cases is thought to be the result of a 'known cause'. These exclusions are
      invalid. It is always valid, however, to exclude all subjects with 'known' causes
      from a study, cases from the numerator and the people or person-time at risk from
      the denominator (or from the control series in a case-control study). If the
      exclusions from the denominator would be negligibly small or the relative number
      of excluded cases with 'known' causes is small, then the exclusion of just the
      cases with 'known' causes will introduce little bias.

PMID- 11998546
TI  - Precautions for proactive surveillance.
AB  - Four barriers confront the architects and users of surveillance systems.
      Bonferroni's Bind blunts our ability to act on real safety signals when the
      surveillance scheme is capable of producing realistic but wrong signals just by
      chance. The paradox of definitive data is that the results of a truly
      comprehensive scheme become untestable because there is no further relevant
      information to be had. Flexible priors augment the first two barriers by
      intensifying our instinctive cautions, and by giving almost any claim the
      appearance of empiric proof. The poverty of tabular summaries is that they
      presuppose the existence of relevant categories for tabulation, and that they
      fail to persuade. The resolution for proactive surveillance is sen/cen: high
      sensitivity to signals and vigorous censoring to filter out the noise.

PMID- 11998547
TI  - Wheezing lower respiratory disease and vaccination of full-term infants.
AB  - PURPOSE: There have been speculations that increases in vaccinations have caused
      recent increases in wheezing lower respiratory disease during infancy. We assess
      possible associations between vaccines and incidence of wheezing in full-term
      infants. METHODS: We conducted a matched case-control study of full-term infants
      born into the Kaiser Permanente Northwest health plan during 1991-1994 and
      continuously enrolled for at least 12 months (n = 1366 case-control pairs).
      Potential cases of wheeze were ascertained from medical care databases and
      verified by chart review. Vaccinations, demographic factors, and wheeze risk
      factors were abstracted from charts. Adjusted relative risks of first onset of
      wheeze during post-vaccination exposure windows were estimated by conditional
      logistic regression. We also conducted case-series analyses of wheeze onsets.
      RESULTS: We found no evidence that risk of wheeze during infancy is associated
      with recency of vaccination with whole-cell pertussis (DTP), hepatitis b (HBV),
      Haemophilus influenzae type b (HIB), oral polio (OPV), or measles, mumps and
      rubella (MMR) vaccines. We also found no evidence that risk of first wheeze is
      associated with exposure to HBV or MMR. CONCLUSIONS: Recent increases in wheezing
      during infancy do not appear to be related to increases in vaccinations of full
      term infants.

PMID- 11998548
TI  - A comparison of measures of disproportionality for signal detection in
      spontaneous reporting systems for adverse drug reactions.
AB  - PURPOSE: A continuous systematic review of all combinations of drugs and
      suspected adverse reactions (ADRs) reported to a spontaneous reporting system, is
      necessary to optimize signal detection. To focus attention of human reviewers,
      quantitative procedures can be used to sift data in different ways. In various
      centres, different measures are used to quantify the extent to which an ADR is
      reported disproportionally to a certain drug compared to the generality of the
      database. The objective of this study is to examine the level of concordance of
      the various estimates to the measure used by the WHO Collaborating Centre for
      International ADR monitoring, the information component (IC), when applied to the
      dataset of the Netherlands Pharmacovigilance Foundation Lareb. METHODS: The
      Reporting Odds Ratio--1.96 standard errors (SE), proportional reporting ratio-
      1.96 SE, Yule's Q--1.96 SE, the Poisson probability and Chi-square test of all
      17,330 combinations were compared with the IC minus 2 standard deviations.
      Additionally, the concordance of the various tests, in respect to the number of
      reports per combination, was examined. RESULTS: In general, sensitivity was high
      in respect to the reference measure when a combination of point- and precision
      estimate was used. The concordance increased dramatically when the number of
      reports per combination increased. CONCLUSION: This study shows that the
      different measures used are broadly comparable when four or more cases per
      combination have been collected.

PMID- 11998549
TI  - Risk of irritable bowel syndrome among asthma patients.
AB  - BACKGROUND: An association between Irritable Bowel Syndrome (IBS) and bronchial
      hyper-responsiveness has been suggested. Only a few studies have specifically
      studied the association between IBS and asthma. AIM: To estimate the incidence
      rate of IBS among asthma patients and to compare it with the general population.
      We also examined the association between use of asthma drugs, specifically
      corticosteroids, and IBS. METHODS: Population-based cohort study using the
      General Practice Research Database (GPRD) in the UK. The cohort comprised a
      random sample of 50,000 asthma patients aged 10-79 years and a similar number of
      sex- and age-matched individuals free of asthma and identified from the source
      population. A nested case-control analysis was performed within the asthma cohort
      to examine the association between asthma drugs and IBS. RESULTS: The incidence
      rate of IBS in the asthma cohort was 2.5 per 1000 persons-years and 2.0 in the
      general population. The relative risk (RR) was 1.3 (95% CI 1.1-1.5). A medical
      history of neurotic and psychologic disorders, pain-related diseases and
      gastroenteritis were all associated with the occurrence of IBS. In the asthma
      cohort, current users of oral steroids presented a RR of 0.5 (95% CI 0.2-1.2) for
      developing IBS. The risk estimate was similar in short- and long-term users of
      steroids. CONCLUSIONS: We found a slightly increased risk of IBS in asthma
      patients compared to the general population and that the risk of IBS was reduced
      by use of oral steroids in asthma patients. Additional studies in the general
      population are necessary in order to confirm whether use of corticosteroids
      irrespective of asthma has a protective effect on the risk of IBS.

PMID- 11998550
TI  - How do pharmaceutical companies handle consumer adverse drug reaction reports? An
      overview based on a survey of French drug safety managers and officers.
AB  - It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have
      been continuously increasing for the last few years in Europe. This probably
      results from the influence of United States (US) market where the patients feels
      justified in telephoning the pharmaceutical companies directly with queries
      regarding their treatment. The growing number of alternative sources of
      information (e.g. health and popular magazines, spots on radio and TV etc.) to
      which a consumer is exposed has added to this growth too. The changing
      relationship between patients and doctors may also contribute to this phenomenon.
      It is then interesting to evaluate the way pharmaceutical companies currently
      deal with consumer ADR reports. The management of consumer ADR reporting was
      investigated by means of a questionnaire sent to 46 French drug safety managers
      and drug safety officers (DSOs) of multinational pharmaceutical companies. The
      analysis of the survey stressed the fact that pharmaceutical companies should be
      prepared to face up to an increase in the number of consumer ADR reports. It
      clearly appears that the consumers who telephone to register side-effects should
      be forwarded to a trained DSO with medical or pharmaceutical background and the
      communication skills acquired through specific training. This person should also
      be able to release adequate product information validated by his/her own company.
      The influence of the US market seems to be changing the way pharmaceutical
      companies deal with consumer ADR reports. Nowadays, these reports are entered
      into a drug safety database by most of the companies without previously having
      contacted the patient's general practitioner (GP) or specialist for medical
      confirmation. Lastly, the drug safety managers and DSOs consulted have divided
      opinions about the usefulness of call centres and e-mails as tools for ADR
      reporting. But both tools are globally rejected by the pharmaceutical companies
      as a reliable means of reporting. As stated in this article, the reporting of
      ADRs via e-mail would cause real problems for the drug safety units. Finally,
      they consider that telephone call centres should be restricted to a specific
      communication problem such as crisis management or Dear Dr letters.

PMID- 11998551
TI  - Antihypertensive drug treatment in a Swedish community: Skaraborg Hypertension
      and Diabetes Project.
AB  - PURPOSE: To describe and compare the pattern of antihypertensive drug
      prescriptions during different time periods. METHODS: Antihypertensive
      prescriptions were registered in all patients who underwent an annual follow-up
      during 1998 (n = 984), 1992-1993 (n = 924), and 1981 (n = 689), at the
      hypertension outpatient clinic in primary health care, Skara, Sweden. RESULTS:
      From 1981 to 1998 the total prescriptions of thiazides declined from 61 to 10% (p
      < 0.001), whilst prescriptions of calcium antagonists increased from 4 to 30% (p
      < 0.001), and ACE inhibitors from zero to 23% (p < 0.001). Prescriptions of
      calcium antagonists and ACE inhibitors increased during 1990-1995, but during
      1996-1998 a significant decrease in primary prescriptions of calcium antagonists
      was demonstrated (OR: 0.15; 95% CI: 0.06-0.36). During all periods, females were
      more frequently treated with older types of antihypertensive drugs than males. In
      the analysis of total prescriptions in 1998 women were prescribed calcium
      antagonists (OR: 0.59; 95% CI: 0.45-0.78) and ACE inhibitors (OR: 0.43; 95% CI:
      0.31-0.58) less frequently than men. CONCLUSION: There were significant changes
      in type of antihypertensive drugs used, both by time and between genders. Changes
      during the latest years indicate that the prescription pattern can be greatly
      influenced by new scientific reports and economic debate.

PMID- 11998552
TI  - Drug or symptom-induced depression in men treated with alpha 1-blockers for
      benign prostatic hyperplasia? A nested case-control study.
AB  - PURPOSE: Regulatory authorities have raised concern that alpha 1-blockers,
      prescribed predominantly for benign prostatic hyperplasia (BPH), may be
      associated with an increased risk of depression. The aim was to assess the risk
      of depression with alpha 1-blockers independently of that associated with
      symptoms being treated and concurrent illness. METHODS: Using a study population
      registered on the UK General Practice Research Database, and taking a
      prescription for an antidepressant as a proxy for clinical depression, we
      performed: (a) cohort analyses comparing the incidence of depression in current
      users of alpha 1-blockers versus non-users, and in men with BPH versus those
      without. (b) A nested case-control analysis looking at the association between
      depression and alpha 1-blocker exposure, accounting for the presence of BPH and
      other illness. RESULTS: In the cohort analyses, risk of depression was
      significantly higher in men with BPH compared to those without (IRR 2.17, 2.12
      2.22), but was not significantly different for men exposed to alpha 1-blockers
      versus those unexposed when adjusted for the presence of BPH. Cases of depression
      were more likely to have pre-existing BPH (crude OR 2.09, 2.02-2.15) than
      controls. After adjusting for concurrent illness (using number of GP visits as a
      proxy) and the presence of BPH (adjusted OR 1.38, 1.33-1.43), there was no
      association with depression for exposure to any alpha 1-blocker (adjusted OR
      1.03, 0.90-1.18). CONCLUSIONS: This study did not suggest that the prescribing of
      alpha 1-blockers increases the risk of being depressed. The association
      highlighted by spontaneous reporting systems appears to be explained by
      confounding by concurrent disease.

PMID- 11998553
TI  - Health needs, drug registration and control in less developed countries--the
      Peruvian case.
AB  - A number of factors influence how medicines are used in each community, but drug
      registration is the initial and usually necessary step. In the course of an
      external advisory consultation, the list of approved medicines in Peru in 1998
      was examined. Of 1672 newly approved forms, 119 were of 49 new chemical entities.
      Sildenafil, meloxicam, nimesulide, candesartan, irebesartan, naratriptan,
      trovafloxacin and grepafloxacin were among them. Several aspects about the new
      global drug situation and 'real' health needs versus 'induced' health needs are
      discussed from this example.

PMID- 11998554
TI  - Adverse drug reactions as a cause for admissions to a department of internal
      medicine.
AB  - PURPOSE: To assess the occurrence and pattern of adverse drug reactions as a
      cause for acute hospital admission. METHODS: In 681 randomly selected patients,
      acutely admitted to a clinic of internal medicine at a Swedish university
      hospital, information was collected from their medical records about current
      symptoms and use of drugs, previous diseases and the results of medical
      investigations and tests. In addition, a standardized interview according to a
      questionnaire was carried out. A group of experts in clinical pharmacology
      assessed the data obtained from the patients' case records and the results of the
      interviews, and then, according to WHO criteria, judged the probability that an
      adverse drug reaction could have caused or contributed to the actual admission to
      hospital. RESULTS: Out of the 681 cases included, 94 (13.8%) had symptoms and
      signs that were judged as drug-related and that had caused or contributed to the
      admission. Eighty-two patients (12.0%) had altogether 99 symptoms that were
      classified as adverse drug reactions. Of these, 91% were type A reactions. The
      relationship between the medication and the reaction was judged certain in eight,
      probable in 17, and possible in 74 cases. The most common adverse drug reactions
      were cardiovascular (36.3%). Twelve patients (1.8%) had symptoms indicating
      intoxications. CONCLUSIONS: The prevalence of drug-related problems causing or
      contributing to admission to a clinic of internal medicine is high and is
      dominated by type A reactions, i.e. reactions in principle predictable and
      preventable. This implies a possibility to increase drug safety by preventive
      measures.

PMID- 11998555
TI  - An epidemiological pattern of poisoning in India.

PMID- 11998556
TI  - Maintaining confidentiality in research data.

PMID- 11998557
TI  - Current literature in. Pharmacoepidemiology and drug safety.

PMID- 11998558
TI  - [The significance of Helicobacter pylori infection from the clinical viewpoint].

PMID- 11998559
TI  - [Epidemiology and pathogenesis of Helicobacter pylori infection].
AB  - Since Marshall and Warren reported the first isolation of Helicobacter pylori
      basic and clinical research on pathogenesis and epidemiology of Helicobacter
      pylori infection have been tremendous. Childhood is clearly established as the
      period of major risk for Helicobacter pylori acquisition. The transmission
      pathways may be several including the oral-oral, the gastro-oral or the fecal
      oral transmission route. The colonization of Helicobacter pylori occurs
      exclusively in the gastric mucosa or in areas of gastric metaplasia especially in
      the duodenum. Helicobacter pylori possesses several factors to adhere to the
      epithelial cells and to cause mucosal damage. The acquisition of Helicobacter
      pylori always induces a chronic gastritis. The development to clinical
      manifestations (peptic ulcer or gastric cancer) are further dependent on specific
      bacterial strain virulence factors as well as on host and environment factors.
      The mechanisms involved in the inflammatory process have been elucidated in great
      detail and will further be focused and related to specific associated disease
      development.

PMID- 11998560
TI  - [Helicobacter pylori: virulence factors, resistance and diagnosis].
AB  - Helicobacter pylori disposes of various virulence factors such as urease,
      vacuolating cytotoxin and the cag-pathogenicity island which--though not alone,
      but possibly in conjunction with host-specific factors--may explain the varying
      course of the infection (asymptomatic, dyspepsia, ulcer, distal gastric
      carcinoma). Increasing resistance to macrolide antibiotics and the lack of new
      therapeutic approaches makes treatment of the infection increasingly difficult.
      The resultant call for a strict indication for treatment is in obvious contrast
      to the finding that Helicobacter pylori represents the major risk factor for
      gastric carcinoma and eradication would therefore be absolutely desirable.
      Increased use of culture and susceptibility testing would be desirable for the
      purpose of therapy optimization but also for reasons of resistance epidemiology.
      The indication for diagnostic screening should be guided by the treatment
      indications as proposed by the guidelines of the Maastricht Consensus Conference
      2-2000. In addition--and regardless of clinical picture--therapeutic follow-up
      primarily relying on non-invasive tests (13C urea breath test, stool antigen
      test) should be a matter of course.

PMID- 11998561
TI  - [Helicobacter pylori infection--clinical aspects and indications for treatment].
AB  - Helicobacter pylori (H. p.) causes active chronic antrum gastritis in all
      infected patients. In a relatively small percentage complications of H. p.
      gastritis including duodenal ulcer, gastric ulcer, giant fold gastritis,
      lymphocytic gastritis, autoimmune gastritis, gastric carcinoma and gastric MALT
      lymphoma may develop. Strongly recommended indications for eradication therapy
      include gastroduodenal ulcer disease, giant fold gastritis, lymphocytic
      gastritis, autoimmune gastritis, gastric MALT lymphoma, atrophic gastritis,
      corpus-predominant gastritis, post gastric cancer resection and patients who are
      first degree relatives of gastric cancer patients. Eradication therapy is
      controversial in patients with gastroesophageal reflux disease, functional
      dyspepsia and in patients in whom treatment with nonsteroidal antiinflammatory
      drugs (NSAID) or long-term treatment with proton pump inhibitors (PPI) is
      planned.

PMID- 11998562
TI  - [Significance of Helicobacter pylori infection for stomach lymphoma and stomach
      carcinoma].
AB  - The discovery of Helicobacter pylori in 1983 revolutionised pathogenetic
      hypotheses of almost all gastric diseases and markedly enhanced research
      especially in the field of malignant tumours of this organ. Based on
      epidemiological studies indicating an association of H. pylori infection and
      malignant gastric tumours the WHO classified this bacterium as "class I
      carcinogen" already in 1994. Although the high prevalence of this germ worldwide
      is sharply contrasting the low incidence of gastric carcinomas and lymphomas its
      role as independent risk factor in the carcinogenesis of these tumours today is
      reasonably evidence-based. Thus, epidemiologists are calculating a reduction of
      80% of all MALT-type lymphomas and of about 60% of gastric "non cardia"
      carcinomas in the scenario of an "H. pylori-free" world. However, complete
      remission of 80% of early lymphomas of MALT-type confined to mucosa and
      submucosa, only, after antibiotic eradication of the bacterium is well
      established in literature and follow-up data are confirming sustained response
      after years. The strength of impact of an H. pylori infection on gastric
      carcinogenesis will be figured out by prospective studies on a non infected
      population in the future.

PMID- 11998563
TI  - [Therapy of Helicobacter pylori infection: "Who to treat, how to treat?"].
AB  - Seventeen years after detection of Helicobacter pylori as the pathogenetic factor
      in a variety of gastroduodenal diseases, current treatment options are about 90%
      effective in eradicating the bacteria and thereby curing the affiliated
      disorders. In 1987 successful therapy has been shown to reduce relapse rates of
      duodenal and gastric ulcers dramatically and clinicians all over the world
      started to perform a still ongoing vast number of trials searching for the most
      effective first--and in case of failure, second line-treatment options. The
      results of these trials led to strictly evidence based and generally accepted
      guidelines formulated by Consensus Reports. The main questions "who to treat" and
      "how to treat" can be answered by using the categories "strongly recommended
      indications", "advisable indications" that leave some space for individual
      decisions, and consideration of first and second time eradication therapies
      together as a package. Treatment has become simple: three drugs, twice daily for
      one week. All available protone pump inhibitors (PPI) have been shown to be
      effective and presently there is only a few antibiotic agents used in combination
      and defined dose, proven to ensure treatment success. The future will encounter
      clinicians with problems concerning patient compliance, antibiotic resistance and
      more effective second and even third line therapies. This paper will focus on two
      subjects: indications ("who to treat") and evidence-based eradication regimens
      ("how to treat") in a reasonable setting close to everyday clinical practice.

PMID- 11998564
TI  - [Medical problems of handedness].
AB  - Handedness is one example of many forms of behavioral lateralization seen in
      humans. In the present review the practical relevance and the problems of left
      handedness are discussed. Left-handedness has existed in a small subset of the
      human population, approximately 8%, since the origin of man. The incidence of
      left-handedness as usually defined is consistent among human populations. An
      understanding of handedness may lead to valuables clues as to how the brain
      becomes organised in the way it does. Several authors suggested a pathological
      handedness explaining the origin of laterality in man. There is a general
      agreement that sinistrality can occur as a result of pre- or perinatal damage to
      the left hemisphere. A disproportionate number of sinistrals is found in clinical
      populations. The review indicates that there is no sure evidence to suggest that
      left-handedness is a pathological sign.

PMID- 11998565
TI  - [Cancer prevention with green tea: reality and wishful thinking].
AB  - Different processing of the leaves of the tea plant Camellia sinensis yields
      green or black tea, the subject of numerous investigations on the preventive
      effects on chronic degenerative diseases. The tea polyphenols, in particular (-)
      epigallocatechin gallate (EGCG) were found to account for most of the protective
      effects. Since the concentration of EGCG is 5 times higher in green than in black
      tea, it is assumed that green tea possesses a greater preventive potential.
      Protection against cancer and cardiovascular diseases are the most important
      biomedical effects. In experimental models the preventive activity of tea is well
      documented for tumors at many organ sites. In humans, tea was reported to be
      protective against tumors of the lung, the gastrointestinal tract and the liver.
      Tea polyphenols, especially EGCG, were shown to exert cancer-protective activity
      by the following mechanisms: they inhibit the metabolic activation of carcinogens
      and induce at the same time detoxifying enzymes. They inhibit signaling pathways
      controlling cell proliferation and tumor growth such as protein kinase C and the
      release of tumor necrose factor-alpha from cells. Tea polyphenols reactivate
      processes which are impaired in tumor cells, such as the programmed cell death
      and the tumorsuppressor gene p53. Finally, tea polyphenols can also block
      angiogenesis leading to a starvation of the tumor. By inactivation of proteolytic
      enzymes they inhibit the development of metastases. This short review summarizes
      relevant recent findings on the protective effects of green tea constituents.

PMID- 11998566
TI  - [Poverty, illness, prayer--thoughts on contemplating the votive painting of St.
      Notburga].
AB  - A votive painting in the chapel of St. Donatus in Pavlovec (northern Croatia)
      from the 18th century depicts St Notburga of Eben with two paupers, a shepherd
      and an invalid. Although generally venerated as patron-saint of peasants and
      maids, Notburga seems to have captured the imagination of the anonymous painter
      as the helper of the poor and underprivileged. The vicious circle of poverty and
      disease is evoked by this painting, as well as the popular belief in divine
      assistance by supplication to patron saints.

PMID- 11998567
TI  - [Evidence-based health care--critical inquiries from the medical ethics
      background].
AB  - Evidence-based medicine already plays an important role in clinical practice and
      in allocation decisions in health care. It is therefore of particular importance
      to acknowledge the ethical as well as the conceptual, methodological,
      epistemological and practical objections that have been articulated. A
      comprehensive medico-ethical evaluation of many of these caveats can be
      undertaken only in the context of a concrete health care system. The EU-sponsored
      EVIBASE project deals with these very issues. However, it is up to evidence-based
      medicine to prove it can comply with its own standards and counter the skeptical
      or critical arguments.

PMID- 11998568
TI  - MR imaging of benign hepatic tumors.
AB  - Use of a state-of-the-art pattern recognition approach and the combination of
      various MR sequences and contrast enhancement techniques makes it possible to
      diagnose most benign hepatic tumors with confidence.

PMID- 11998569
TI  - MR imaging of iron depositional disease.
AB  - This article discusses the physiology of iron metabolism in humans. The
      pathophysiology and MR imaging findings of disorders that result in iron
      deposition in the liver are described. Emphasis is placed on genetic, clinical,
      and imaging findings of hemochromatosis. Radiologists should familiarize
      themselves with the patterns of iron deposition on MR images in order to suggest
      a potential etiology, which may not be known at the time of imaging.

PMID- 11998570
TI  - MR imaging of infective liver lesions.
AB  - This article discusses MR imaging of infective liver lesions including pyogenic
      liver abscesses, amebic liver abscesses, echinococcal disease, hepatic fungal
      abscesses, granulomatous hepatic infections, schistosomiasis, and fascioliasis.

PMID- 11998571
TI  - MR imaging of the pediatric liver.
AB  - Applications of MR imaging of the pediatric abdomen are expanding rapidly. New
      techniques of MR imaging, such as MRA or MRCP, are becoming commonplace. MR
      imaging is particularly helpful in the diagnosis and characterization of liver
      and biliary tree disease in children. Consistent and reproducible quality imaging
      is achieved with faster imaging sequences tailored to reduce motion artifacts.
      The lack of radiation, the ability to directly acquire multiple imaging planes,
      and the superior contrast resolution, particularly with the administration of
      gadolinium, have contributed to the acceptance of MR imaging as an invaluable
      tool in the pediatric age group.

PMID- 11998572
TI  - MR imaging of hepatic metastases.
AB  - MR imaging is an excellent diagnostic tool for the detection and characterization
      of liver metastases. The most characteristic finding is peripheral ring
      enhancement on immediate postgadolinium images.

PMID- 11998573
TI  - MR imaging of the gallbladder.
AB  - T2-weighted imaging and MRCP, which have high sensitivity to edema and fluid, are
      paramount in the evaluation of certain gallbladder diseases, such as
      cholelithiasis, cholecystitis, adenomyomatosis, and cystic duct abnormalities.
      Dynamic gadolinium-enhanced MR imaging has the potential to differentiate among
      the many nonspecific-appearing lesions involving the gallbladder. MR imaging may
      not yet replace ultrasound as the workhorse of acute gallbladder imaging.
      Currently, MRCP is an ideal complementary study to inconclusive sonographic
      studies and can help plan surgical intervention in the setting of acute
      cholecystitis. Further investigation of hepatobiliary contrast agents, however,
      may reveal that MR imaging may be considered as first-line imaging in the acute
      setting.

PMID- 11998574
TI  - MR imaging of hepatocellular carcinoma.
AB  - In this article, MR imaging features of hepatocellular carcinoma (HCC) are
      described. To better understand the MR imaging features of HCC, recent progress
      regarding its etiology, treatment, carcinogenesis, histology, and gross pathology
      will be described. Currently, T2-weighted fast spin-echo with fat saturation, and
      multiphasic dynamic gadolinium-enhanced two-dimensional and three-dimensional T1
      weighted gradient echo imaging provides excellent results for detection and
      characterization of HCC.

PMID- 11998575
TI  - Post-treatment malignant liver lesions. MR imaging.
AB  - MR imaging is very accurate in the diagnosis and staging of tumors and in
      surgical planning. MR imaging is also an excellent method for evaluation of the
      liver after surgical resection, systemic or local tumor therapies, and liver
      transplantation. It permits early recognition of complications and the presence
      of recurrent tumor, providing an opportunity to repeat treatment or use
      alternative treatment. Surgical resection remains the standard therapy for
      treating liver metastases. The relatively small number of patients who are
      candidates for curative resection have provided impetus for the implementation
      and improvement of other techniques. The variety of techniques and the
      sensitivity for contrast enhancement have made MR imaging an ideal method to
      follow the response of tumors to various treatment approaches. The appearance of
      tumor recurrence and the response to treatment are relatively consistently shown
      on MR images; however, the time course of change in lesion appearance has not
      been fully elucidated, particularly in the setting of chemotherapy. Evaluating
      the response to chemotherapy is rendered complex because of the longer duration
      of the therapy, the types of response that various chemotherapeutic agents
      engender, the method of action of this therapy and the time of imaging in
      relation to therapy. The various local therapies share some general principles of
      action, and many have similar MR imaging findings. Some local therapies are
      effective only with certain malignancies (e.g., alcohol therapy and HCC), whereas
      other therapies are more limited because of the size of the tumor kill zone
      (e.g., interstitial laser therapy). We are in the early stages of using MR
      imaging to guide local therapies and to monitor response during treatment in real
      time. This appears to be an important future direction for MR imaging. The role
      of MR imaging in liver transplantation involves pre- and postoperative
      investigation of both donors (in the case of living-related transplantation) and
      recipients. These issues are described further in the section on MR imaging of
      liver transplantation.

PMID- 11998576
TI  - Cirrhosis: MR imaging features.
AB  - The intent of this article is to provide a comprehensive review of MR imaging
      findings of cirrhosis and discusses clinical implications. Areas of focus
      include: (1) Morphologic changes of the liver in advanced cirrhosis and in early
      cirrhosis, (2) the frequency and imaging spectrum of intra- and extrahepatic
      changes in cirrhosis such as regenerative nodules, nodular liver surface, hepatic
      iron deposition, fibrosis, dilation of right inferior phrenic artery,
      gastrointestinal wall thickening, and portal hypertension, (3) serial MR findings
      of clinically progressive cirrhosis, (4) newly described MR sign of cirrhosis (an
      expanded gallbladder fossa sign), and (5) complications after liver
      transplantation. Understanding these MR features related to cirrhosis is helpful
      in clinical MR practice.

PMID- 11998577
TI  - Imaging the fatty liver.
AB  - Even though various imaging techniques are available to detect fat, chemical
      shift imaging is the most accurate for both qualitative and quantitative
      measurement of fat. It can be very useful in liver studies, not only because it
      definitively demonstrates fatty liver but also because it improves lesion
      detection and characterization in some cases.

PMID- 11998578
TI  - An advance triage system.
AB  - This paper describes the redesign of the triage process in an Emergency
      Department with the purpose of improving the patient flow and thus increasing
      patient satisfaction through the reduction of the overall length of stay. The
      process, Advance Triage, allows the triage nurse to initiate diagnostic protocols
      for frequently occurring medical problems based on physician-approved algorithms.
      With staff and physician involvement and medical specialist approval, nine
      Advance Triage algorithms were developed-abdominal pain, eye trauma, chest pain,
      gynaecological symptoms, substance abuse, orthopaedic trauma, minor trauma,
      paediatric fever and paediatric emergent. A comprehensive educational program was
      provided to the triage nurses and Advance Triage was initiated. A process was
      established at one year to evaluate the effectiveness of the Advance Triage
      System. The average length of stay was found to be 46 min less for all patients
      who were advance triaged with the greatest time-saving of 76 min for patients in
      the 'Urgent' category. The most significant saving was realized in the patient's
      length of stay (LOS) after the Emergency Physician assessed them because
      diagnostic results, available during the initial patient assessment, allowed
      treatment decisions to be made at that time. Advance Triage utilizes patient
      waiting time efficiently and increases the nurses' and physicians' job
      satisfaction.

PMID- 11998579
TI  - Consent to treatment in the A&E department.
AB  - Compared to other areas in nursing, nurses working in A&E Departments encounter a
      wide range of difficult and specific issues relating to consent to treatment,
      whether they are acting independently as nurse practitioners or carrying out the
      treatment prescribed by doctors. The law of consent must be taken into account in
      our daily practice to avoid a claim of battery or negligence from our patients.
      Emergency treatment can be given under the doctrine of necessity if an adult
      patient lacks capacity to give consent, but treatment cannot be imposed on
      competent adults who refuse it. Assessment of capacity may be difficult. Patients
      with mental disorders can pose specific consent difficulties, depending on
      whether the proposed treatment is directly related to the mental disorder.
      Problems may also arise from adult patients who refuse treatment due to undue
      influence from others. Obtaining consent to treatment for children depends on
      their age, maturity and understanding. Specific difficulties may arise if the
      child's wishes conflict with those with parental consent, or when those with
      parental responsibility unreasonably refuse to give consent.

PMID- 11998580
TI  - Is the radiation of chest pain a useful indicator of myocardial infarction? A
      prospective study of 541 patients.
AB  - In recent years it has been claimed that in those presenting with chest pain, the
      extent of pain radiation may be predictive of MI and that women's and men's
      pattern of pain radiation differs. This prospective study therefore investigated
      whether there were differences in pain radiation between those with and without
      MI and according to gender. Patients (n = 541) presenting to a CCU with an
      episode of chest pain were asked to indicate on a body map the region of pain
      radiation they experienced at the time of symptom onset. As expected, radiation
      to the left and/or to right shoulder/arm was significantly higher in the MI
      group. Women with MI experienced more chest pain radiating to the right
      arm/shoulder (P = 0.0005), upper right region (P = 0.0006) and arm/shoulder than
      those without MI. Additionally, women with MI also described more pain radiation
      in the front neck (P = 0.015) area, and the right shoulder/arm (P = 0.02) than
      their male counterparts. A third of these women also experienced more pain
      radiating to the back (P = 0.005). The premise of greater chest pain distribution
      amongst those with an MI could not be confirmed. Nevertheless, the study
      identified significant differences amongst women with MI, the discussion analyses
      the implications for practice.

PMID- 11998581
TI  - Working with patients: developing a service user group in one A&E department.
AB  - Recognition, by personnel in one emergency department, that the modern emergency
      service has to be responsive and sensitive to the needs of patients in the local
      community, led to a project aimed at setting up a service user council. The
      purpose of the council was to provide opportunities for both staff and service
      users to play an active part in service development and evaluation. It was
      anticipated that such an initiative would 1) promote the development of a patient
      centred service; 2) recognize the value of multidisciplinary work in relation to
      patient care and 3) identify areas of priority for service development. In
      addition to this, it was anticipated that issues associated with patients'
      expectations of the service, as well as the ways in which the service was
      accessed could also be addressed.

PMID- 11998582
TI  - A realistic view of domestic violence screening in an emergency department.
AB  - Sutherland Hospital is a district hospital serving The Sutherland Shire, a
      metropolitan area of Sydney. It has a population of approximately 220,000 which
      is predominantly Anglo-Saxon in ethnic origin. The Emergency Department provides
      emergency services for 30,000 new patients per annum. New South Wales Department
      of Health obtained Commonwealth funding from Partnerships Against Domestic
      Violence to pilot routine screening for domestic violence within 2 Area Health
      Services. One of the participating sites was the Emergency Department in South
      East Sydney Area Health Service. The aim was for nursing and medical staff to
      screen, for three months, all women sixteen years old and over. Information cards
      on state-wide domestic violence resources and referral flow charts were developed
      for the pilot. Staff undertook training and issues were addressed prior to the
      screening. In this article we will discuss the findings, including the rate of
      screening by the staff, disclosure rate of domestic violence, and action taken on
      disclosure. We will then proceed to explain the difficulties in undertaking
      screening within an Emergency Department, and make recommendations for those
      Emergency Departments interested in commencing screening.

PMID- 11998583
TI  - Serving on an enquiry panel: one nurse's experience.
AB  - Liz Whelan is Clinical Nurse Manager at Gloucestershire Royal Hospital and
      recently served on the panel of inquiry into the death of a patient in A&E at
      Whipp's Cross Hospital, London (Mr Thomas Rogers, Review of Care at Whipps Cross
      Hospital Accident and Emergency Department, Report of the Panel of Inquiry,
      October 2001). The following is a transcript of the talk (supported by slides)
      she gave as a concurrent session at the RCN A&E Association's Conference in
      November 2001.

PMID- 11998585
TI  - Dilemma. A tannoy call for help on a plane.

PMID- 11998586
TI  - Med-psych drug-drug interactions update.

PMID- 11998587
TI  - Assessment and treatment of functional disorders in general practice: the
      extended reattribution and management model--an advanced educational program for
      nonpsychiatric doctors.

PMID- 11998588
TI  - Joint commissioning. Going halves.
AB  - Joint commissioning and provision of mental health services in Somerset failed to
      produce significant benefits to users over its first two years. Users considered
      access to services deteriorated and concerns remain that there is no alternative
      to hospital admission in crises. Users and carers were included as non-voting
      members of the commissioning board, but users felt less involved in care planning
      than previously. The combined health and social care trust does not seem to have
      delivered anything which has not been achieved elsewhere without the transfer of
      social care staff to a new employer.

PMID- 11998589
TI  - NHS scrutiny. Powers of observation.
AB  - Local authority scrutiny of the NHS, to come into effect in January next year,
      will bring health services into local politics more directly than ever before.
      The scrutiny committees will be able to call chief executives and directors to
      account and scrutinize service decisions. Health organisations should become
      involved in scrutiny arrangements now.

PMID- 11998590
TI  - NHS recruitment. School daze.
AB  - School pupils from ethnic minorities do not see the NHS, and nursing in
      particular, as offering attractive job opportunities, even in an area of high
      unemployment. Nursing is perceived as menial, very poorly paid and stressful.
      Trusts need to improve their literature and send staff into schools to improve
      recruitment.

PMID- 11998591
TI  - Inconclusive guidance will merely gather dust.

PMID- 11998592
TI  - Silver. I: Its antibacterial properties and mechanism of action.
AB  - Silver products have two key advantages: they are broad-spectrum antibiotics and
      are not yet associated with drug resistance. This article, the first in a two
      part series, describes the main mechanism of action of this metallic element.

PMID- 11998593
TI  - Evaluation of the stability and efficacy of rhGM-CSF as a topical agent in a gel
      formulation.
AB  - OBJECTIVE: It has been reported that recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF), applied as a solution or an emulsion,
      improves wound healing. In order to confirm these data, the wound-healing
      efficacy of this growth factor was studied in a murine model. METHOD: In this
      double-blind randomised study, murine excisional wounds were treated with either
      sterilised rhGM-CSF gel (10 micrograms/cm2) or a sterilised placebo gel (control
      group). rhGM-CSF was applied at dosages of 10 micrograms/cm2/day to wounds until
      complete closure occurred. RESULTS: rhGM-CSF stability in gel formulation was
      excellent during the first week but decreased thereafter. Full wound healing
      occurred within 9.7 days (mean time) in the intervention group compared with 10
      days in the control group. This difference was not statistically significant.
      Histological evaluation of the healed wounds indicated that there was a similar
      percentage of neutrophils in the cellular infiltrate in both groups. CONCLUSION:
      rhGM-CSF sterile gel had an excellent safety profile and was easy to use, but did
      not significantly accelerate the healing rate in this model.

PMID- 11998594
TI  - Digital imaging versus conventional contact tracing for the objective measurement
      of venous leg ulcers.
AB  - OBJECTIVE: This study aimed to compare the accuracy and inter-observer
      reproducibility of leg ulcer measurements made using digital images and
      conventional contact tracing. METHOD: The accuracy of measurements made with
      these two methods by four observers of 11 shapes with a known area was assessed.
      The time taken to do this was also measured. Following this, the accuracy and
      inter-observer reproducibility of the two methods was measured for patients with
      leg ulcers presenting to the vascular clinic, with contact tracing as the
      reference. RESULTS: For the reference shapes, both methods had a mean error of
      less than 5%. Contact tracing significantly underestimated the area by 3.9% (p <
      0.05), while digital tracing showed no significant error. Digital tracing was
      quicker than contact tracing, especially for larger shapes (p < 0.05). For leg
      ulcers, there was no significant difference between area measurements made by the
      two methods. Inter-observer variation of digital tracing was greater for the
      ulcers than the reference shapes. This was due to differences in subjective
      interpretation and technical problems in recording some images. CONCLUSION:
      Measurement of leg ulcer area using computer-aided tracing of digital camera
      images is more accurate and quicker than contact tracing provided that
      appropriate care is taken when taking the pictures. Digital images offer
      considerable advantages in the shared hospital-community care of patients with
      leg ulcers.

PMID- 11998595
TI  - Moist wound healing: does the theory apply to chronic wounds?
AB  - Winter's research on moist wound healing continues to exert a strong influence on
      tissue viability practice. But does this theory, which is based on porcine acute
      wounds, apply to human chronic wounds. This review explores the evidence.

PMID- 11998596
TI  - Effect of Traumacel P on the growth of human dermal fibroblasts in vitro.
AB  - OBJECTIVE: It has been postulated that Traumacel P, a haemostatic powder, might
      assist the wound-healing process. This in vitro study investigated the effect of
      the powder on human dermal fibroblasts. METHOD: Experiments using fibroblasts
      from a 50-year-old donor were carried out using suspensions of Traumacel P
      ranging from 0.1 to 10.0 mg/ml. Dulbecco's Modified Eagle Medium with 10% or 0.4%
      foetal calf serum (FCS) and 5.5 mM or 25 mM glucose was used. The powder was
      either placed in contact with the cells or separated from them by a porous
      membrane. The response of the fibroblasts was assessed using the MTT assay.
      RESULTS: Concentrations of 0.5 mg/ml and 1.0 mg/ml stimulated the metabolic
      activity of the fibroblasts in both high and low glucose medium with 10% FCS,
      regardless of whether the powder was in contact with or separated from the cells.
      The greatest stimulation, to 174% of the controls, was produced by 0.5 mg/ml
      Traumacel P in low glucose/10% FCS with the powder in contact with the cells (p <
      0.0001). Traumacel concentrations ranging from 0.5 to 5.0 mg/ml in 0.4% FCS
      significantly stimulated the metabolic activity of fibroblasts in low glucose
      medium, but not in the high glucose medium. CONCLUSION: These studies indicate
      that direct stimulation of fibroblast proliferation may be one of the ways in
      which Traumacel P aids the healing of ulcers observed in the clinic.

PMID- 11998597
TI  - Clinical trials in wound care. II: Achieving statistical significance.
AB  - Clinical trials must be well designed in order to produce statistically and
      clinically significant results. This article describes the randomisation
      techniques that can prevent bias, the importance of sample size and the concept
      of power analysis.

PMID- 11998598
TI  - Mammography: past--underused, present--underfinanced, future--unavailable?

PMID- 11998599
TI  - FDA approves new drug for gastrointestinal stromal tumors.

PMID- 11998600
TI  - Steps taken to ensure narcotics' availability for legitimate use.

PMID- 11998601
TI  - Computer technology will aid breast cancer detection.

PMID- 11998602
TI  - Older women with breast cancer being managed more aggressively.

PMID- 11998603
TI  - Obesity increases risk of death from breast cancer.

PMID- 11998604
TI  - Maintenance of venous access devices in patients with neutropenia.
AB  - Neutropenia is a common complication in patients with cancer who are undergoing
      chemotherapy. Because of treatment frequency, potential chemotherapy damage to
      peripheral veins and tissues, and pain from multiple venipunctures, venous access
      devices (VADs) often are used in the oncology setting. Although VADs have been
      used for 30 years, no sufficient scientific data exist to support the best care
      and maintenance strategies for their use in patients with neutropenia.
      Understanding the etiology and pathogenesis of VAD-related infections (VAD-RI)
      and the proper steps to prevent or quickly treat it can decrease the likelihood
      that patients with neutropenia will have a fatal response. This article describes
      the differences between VADs, the most common sources of VAD-RI, and the
      treatment of such infections and suggests nursing interventions to help prevent
      VAD-RI.

PMID- 11998605
TI  - New therapeutic options in colon cancer: focus on oxaliplatin.
AB  - Colon cancer is the third leading cause of cancer death in the United States and
      the second leading cause in the Northern, Central, and Southern Americas.
      Appropriate treatment depends on the stage of malignancy, which is determined
      using the tumor-lymph node-metastases system. In stage III disease, adjuvant
      chemotherapy increases disease-free and long-term survival following surgery, and
      chemotherapy is the mainstay of treatment for advanced disease. New therapies are
      being evaluated, including oxaliplatin, a third-generation platinum analogue
      approved as first- and second-line therapy for metastatic colorectal cancer in
      Europe; the drug shows great promise combined with 5-fluorouracil/leucovorin or
      with irinotecan. The dose-limiting toxicity of oxaliplatin is neurologic, which
      can be acute or chronic; this can be prevented or reduced in some cases through
      patient education. Nurses play a critical role in education concerning prevention
      and management of oxaliplatin-related side effects.

PMID- 11998606
TI  - Nursing care of patients receiving Campath.
AB  - Monoclonal antibodies are focused therapies with unique infusion-related
      complications. Campath (alemtuzumab, Berlex Laboratories, Richmond, CA) is
      indicated for the treatment of refractory chronic lymphocytic leukemia and has a
      complicated administration schedule, severe infusion-related toxicity, and
      profound immunosuppressive capability. Ambulatory cancer care is challenging
      simply because of the complex nature of the disease. Management of complicated
      therapies, such as Campath, stretches resources and requires a coordinated effort
      by the healthcare team for successful patient outcomes.

PMID- 11998607
TI  - Radioimmunotherapy for non-Hodgkin's lymphoma with yttrium 90 ibritumomab
      tiuxetan.
AB  - The increasing incidence of non-Hodgkin's lymphoma (NHL), coupled with the lack
      of optimal treatment options, has prompted the development of novel treatments.
      Of these, radioimmunotherapy is one of the most promising. Two of the
      radiolabeled monoclonal antibody therapies being studied in the treatment of NHL
      are yttrium 90 (90Y) ibritumomab tiuxetan and iodine 131 (131I) tositumomab. The
      radionuclides 90Y and 131I emit beta radiation; 131I also emits gamma radiation,
      thus requiring more elaborate precautionary measures to limit radiation exposure.
      The monoclonal antibody portions of the drugs target the CD20 surface antigen
      that is present on the majority of B-cell lymphomas, resulting in direct
      radiation to the targeted cells, as well as indirect targeting of adjacent cells
      (known as the crossfire effect). Clinical trials of 90Y ibritumomab tiuxetan in
      patients with NHL have produced promising results. The safe and effective use of
      radioimmunotherapy requires a multidisciplinary team approach in which nurses
      play a central role.

PMID- 11998608
TI  - CyberKnife: a robotic radiosurgery system.
AB  - The CyberKnife is a radiosurgical system consisting of a linear accelerator and
      robotic arm. Using guidance imaging, the system precisely locates tumors and
      delivers multiple beams of radiation therapy directly to the tumor site while
      minimizing radiation exposure of surrounding tissue. The CyberKnife has the
      capacity to treat tumors up to 6 cm in size and holds promise as a new
      radiosurgery treatment modality.

PMID- 11998609
TI  - Interdisciplinary modular teaching for patients undergoing progenitor cell
      transplantation.
AB  - Patient-education information provided to patients undergoing progenitor cell
      transplantation (PCT) is complex. Patients' and caregivers' inability to process
      this information and apply principles of self-care can result in poor outcomes.
      An interdisciplinary team developed a three-part modular teaching program and
      documentation tool to address the complex informational needs of patients
      undergoing PCT. The modules were designed to reflect information relative to the
      three phases of PCT: pretransplantation, transplantation, and post
      transplantation. The structured content of the documentation tool allows for
      consistent documentation that systematically reflects the content of the patient
      education modules.

PMID- 11998610
TI  - Prophylactic gastrectomy for CDH1 mutation carriers.
AB  - Gastric cancer is difficult to diagnose at an early stage. Signs and symptoms of
      the disease often only occur when advanced or metastatic disease is present. A
      very small number of gastric cancers are hereditary. The mutation to the E
      cadherin gene has high penetrance and confers a lifetime risk of gastric cancer
      of 80% for carriers. Because of the high penetrance of the mutation and the
      difficulty of diagnosing gastric cancer at an early stage, carriers of the
      mutation may be candidates for prophylactic gastrectomy. Although limited data
      are available about the complications and outcomes associated with prophylactic
      gastrectomy, nurses should be knowledgeable about prophylactic surgery for
      hereditary cancers and prepared to answer patients' questions about their
      prevention.

PMID- 11998611
TI  - Understanding peripheral neuropathy in patients with cancer: background and
      patient assessment.
AB  - PN is a troublesome symptom that frequently occurs in patients with cancer and is
      associated with certain neurotoxic chemotherapeutic agents. By understanding the
      basic principles of PN and recognizing the potential toxicities of specific
      chemotherapy drugs, nurses can take an active role in minimizing their
      occurrence. Nursing assessment is critical to early identification of toxicities
      and successful intervention. Nurses need to educate their patients regarding
      potential drug side effects and review safety issues that may put them at risk
      for injury. Patients need to be instructed to report symptoms of PN to their
      nurses and physicians. Healthcare professionals, in turn, need to assess
      neurologic function on a routine basis, monitor those at risk, and intervene when
      appropriate. Ultimately, PN can be recognized as a significant symptom, such as
      pain or fatigue. Current treatment options include both pharmacologic and
      nonpharmacologic therapies, and the success of the treatment often depends on the
      cause. Research is needed to find better and more effective therapies for PN. The
      Neuropathy Association is a national organization that offers patients with PN
      the chance to contact others to share experiences and information to help them to
      cope with symptoms, increase public awareness of the problem, and promote the
      development of better therapies. This organization provides a newsletter,
      information booklets, and activities for members and can be contacted at 800-247
      6968 or www.neuropathy.org.

PMID- 11998612
TI  - Psychoneuroimmunology. Part I: Physiology.

PMID- 11998613
TI  - Febrile nonhemolytic transfusion reactions.

PMID- 11998614
TI  - Amifostine as a radioprotectant.

PMID- 11998615
TI  - Paclitaxel-related hypersensitivity reactions and monitoring recommendations.

PMID- 11998616
TI  - Developing an institutional placebo policy.

PMID- 11998617
TI  - Biotherapy skin reaction.

PMID- 11998618
TI  - [Nursing as a profession for women. How and why the feminization of nursing
      care?].

PMID- 11998619
TI  - [Ailing public health insurance and patients: reform recommendation].

PMID- 11998620
TI  - [Special ACENDIO Conference in Vienna: the world of nursing language is not round
      yet].

PMID- 11998621
TI  - [Otorhinolaryngology--VI: Inhalation therapy--what Celsius already knew].

PMID- 11998622
TI  - [A special life phase reflected by different cultures: changing the image of
      menopause].

PMID- 11998623
TI  - [Insight into the Berlin Trauma Hospital: what doesn't appear on paper].

PMID- 11998624
TI  - [Mobile digital nursing documentation: putting an end to paperwork].

PMID- 11998625
TI  - [Nursing diagnoses and electronic data processing assisted nursing documentation:
      nursing-related status from the nursing viewpoint].

PMID- 11998626
TI  - [Diagnosis-related activity: saves time and yields evidence].

PMID- 11998627
TI  - [Personnel recruitment choices in nursing care: making the right decision with a
      selection of methods].

PMID- 11998628
TI  - [The significance of a project charge: written agreement increases connection].

PMID- 11998629
TI  - [Work requirements in nursing care: innovations for total improvement].

PMID- 11998630
TI  - [Humor training: mastering daily routine with a laugh].

PMID- 11998631
TI  - [Cost-benefit analysis: prevention of occupational dermatoses in geriatric
      nursing].

PMID- 11998632
TI  - [Learning in nursing care: snow from yesterday].

PMID- 11998633
TI  - [Modern data management in ICNP: from local patient record to international
      comparison].

PMID- 11998634
TI  - Nurses explore topic of women, aging.

PMID- 11998635
TI  - Parity--what does it mean and who cares anyway?

PMID- 11998636
TI  - Is hospital nursing dying?

PMID- 11998637
TI  - Chemical dependency: what exactly are we talking about?

PMID- 11998638
TI  - Returning to work: the chemically dependent health care professional.

PMID- 11998640
TI  - For your information: children's exposure to lead still a problem in Nebraska;
      nurses can help.

PMID- 11998642
TI  - Nurses important in tobacco use prevention, control.

PMID- 11998643
TI  - Further study required. ANA examines, updates, sends back "code for nurses".

PMID- 11998644
TI  - Turning point project. Making the right turn: transforming public health in NE.

PMID- 11998645
TI  - How can we find unity in nursing?

PMID- 11998647
TI  - Winter comes early sometimes.

PMID- 11998648
TI  - Palliative nursing care for the patient experiencing end-stage renal failure.
AB  - Caring for the patient with end-stage renal disease poses many challenges for the
      bedside nurse. Yet, how do we care for patients who continue to seek hemodialysis
      with a guarded prognosis? A discussion about palliative care and specific
      interventions used to help improve quality of life for the end-stage renal
      patient is provided. A case example accompanies this article, and highlights the
      interventions used successfully for one such patient.

PMID- 11998649
TI  - Accuracy of ultrasound estimates of urine volume.
AB  - Ultrascan and actual catheterization volumes were compared on 48 urology, general
      surgery, and rehabilitation patients. The findings suggest that mean scan and
      actual urine volumes can be considered equal. In clinical situations where it is
      necessary to determine residual urine volume, the bladder scan technology is a
      good alternative to an invasive catheterization procedure.

PMID- 11998650
TI  - Drug handling questioned.

PMID- 11998651
TI  - Improved continence outcomes with preoperative pelvic floor muscle strengthening
      exercises.
AB  - The results of this study involving the timing of pelvic floor muscle
      strengthening exercises and the return of continence showed that starting
      biofeedback sessions with pelvic floor muscle exercises prior to radical
      prostatectomy surgery improved patient outcomes. A brief overview of male
      incontinence in the general population, risk factors associated with post
      prostatectomy urinary incontinence, the incidence and pathophysiology of post
      prostatectomy incontinence, and the use of biofeedback for treating post
      prostatectomy urinary incontinence are presented to provide the foundation for
      this study.

PMID- 11998652
TI  - Exploring women's beliefs regarding urinary incontinence.
AB  - The purpose of this study was to explore and describe women's beliefs, knowledge,
      and need for education regarding female urinary incontinence (UI). Findings
      suggest that almost half of the women surveyed believed UI was normal. A majority
      believed it is a problem for women, but felt they could not talk about it freely.
      Most knew professional help was available and indicated they would seek help if
      incontinent, but expressed a need for more information. They varied in their
      beliefs regarding the efficacy of various treatment modalities. Implications for
      nursing practice are discussed.

PMID- 11998654
TI  - Majority of men with ED unlikely to report problem to urologist.

PMID- 11998655
TI  - Tissue engineering techniques used in penile reconstruction.

PMID- 11998656
TI  - Lidocaine gel greatly reduces pain for men undergoing rectal prostate biopsy.

PMID- 11998657
TI  - High platelet count multiplies risk following renal cell carcinoma treatment.

PMID- 11998658
TI  - Prostate cancer patients show 79% cure rate with prostate brachytherapy
      treatment.

PMID- 11998659
TI  - Prostate cancer patients blindsided by side effects.

PMID- 11998660
TI  - Survey finds more women experience UTIs than previously thought.

PMID- 11998661
TI  - ED more likely in large-waisted men.

PMID- 11998662
TI  - Prostate health facts.

PMID- 11998663
TI  - Getting ready for certification: urinary tract inflammation and diseases.

PMID- 11998664
TI  - Select herbal remedies used to treat common urologic conditions.

PMID- 11998665
TI  - Providing spiritual care: mutual journey of discovery.

PMID- 11998666
TI  - Resolution. Kansas nursing shortage action plan development.

PMID- 11998667
TI  - Can every nurse give spiritual care?

PMID- 11998668
TI  - Heart and soul of spiritual care. Should nurses provide spiritual care?...

PMID- 11998669
TI  - When the Golden Rule does not apply. Starting nurses on the journey toward
      cultural competence.
AB  - The population of the United States is increasing in cultural diversity. As a
      result, most nurses will have many opportunities to work with patients from
      different cultures. This article discusses the importance of cultural competence
      for nurses. Several educational activities for improving cultural awareness and
      competence are suggested. In particular, a poster session with post-test format
      is described in detail. The article also includes basic definitions related to
      the topic of culture, a brief discussion about the influence of culture on
      advance directives and abuse/neglect, and a list of additional resources.

PMID- 11998670
TI  - Knowledge utilization among experienced staff nurses.
AB  - The purpose of this descriptive exploratory study was to describe the processes
      staff nurses use to select and transfer new knowledge to practice. Eleven
      experienced staff nurses shared 29 examples in which gaining new knowledge
      resulted in changes in thinking or acting in a clinical situation. Findings
      indicated that knowledge utilization originated with the nurse who was active in
      selecting and using new knowledge. Nurses used multiple knowledge utilization
      processes primarily involving factual knowledge and instrumental utilization.
      Often, the decision to move knowledge to practice was based on comparison by
      similarity. There were no variations in utilization processes as nurses floated
      across units. Sources of new knowledge were primarily informal and unit based.
      Implications for staff development focus on developing unit-based resources and
      resource personnel, using innovative ways to introduce new knowledge on the unit,
      and providing time in formal classes for exchange of ideas on using new knowledge
      in practice.

PMID- 11998671
TI  - Developing a crisis response team.
AB  - To handle increased asaultive behavior on three psychiatric units while keeping
      staff and other patients safe, a Crisis Response Team was developed consisting of
      staff from psychiatry and officers from security. A written manual included the
      new policies and procedures and teaching content for verbal and physical
      deescalation techniques. A special inservice education program for assaultive
      crisis management was implemented. This model can be replicated in other areas of
      healthcare where it is necessary to deal with patients who lose verbal or
      physical control.

PMID- 11998672
TI  - Quality improvement practices: enhancing quality of life during mealtimes.
AB  - This article describes ten dining room problems, identified in a nursing home
      study, that needed quality improvement, as well as six quality practices
      suggested for implementation. These six quality practices provide the basis for
      an excellent eating experience characterized by a home-like atmosphere, high
      levels of staff-resident interaction, and increased attention to safety and
      ethical issues. The six practices also could serve as the foundation for a
      facility-wide, cost-effective, quality improvement program.

PMID- 11998673
TI  - When new employee orientation doesn't go as planned. "It is time for Plan B ...
      but, what is Plan B?".
AB  - Although organizations have standard orientation programs for newly hired
      registered nurses, there are times when orientees are unable to meet
      expectations. When this happens, it is important to implement a Plan B--a revised
      orientation program that includes individualized strategies and content--to meet
      the needs of the orientee who is not progressing. This article will identify
      factors that may predict the need for increased orientation time and strategies
      to assist the new employee to complete orientation successfully.

PMID- 11998674
TI  - New graduate RN internship program: a collaborative approach for system-wide
      integration.
AB  - Population growth and aging increase the demand for skilled nurses. Hospitals
      face the challenge of supplying experienced and qualified caregivers. The cost of
      training new nurses remains significant. Nursing educators are pivotal in
      developing the nursing workforce, especially under tightening constraints. This
      article examines the development of a nursing internship program aimed at
      attracting and retaining newly graduated nurses and its effect on retention to
      the institution.

PMID- 11998675
TI  - "Adding pizzazz". A presentation skills workshop for healthcare practitioners.
AB  - Healthcare practitioners are often called upon to share their expertise with
      colleagues. Frequently, expert practitioners are asked to make presentations at
      patient support groups, professional rounds, workshops, meetings, and
      conferences. Often these expert practitioners have not had the opportunity to
      develop strong presentation skills. Consequently, many are reluctant to give
      presentations. When they do present, they often have difficulty communicating
      their ideas effectively. This article describes the creation of a presentation
      skills program for healthcare practitioners. Essential program content is
      identified as well as measures taken to make this an effective, economical, and
      popular training program.

PMID- 11998676
TI  - Essentials for effective communication in oncology nursing: assertiveness,
      conflict management, delegation, and motivation.
AB  - The ability to communicate effectively with a multidisciplinary team in an
      assertive manner to resolve conflict, motivate others, and delegate tasks is a
      prerequisite skill to promote a harmonious work environment. Acquisition of this
      skill is often a combination of inherent attributes and learned experiences. This
      article describes a program on assertiveness, conflict resolution, motivation of
      others, and delegation. Nurses are encouraged to seek expertise from other
      departments (e.g., Human Resources) to help them develop similar programs.

PMID- 11998677
TI  - Help for needy patients.

PMID- 11998678
TI  - Nursing: an international perspective.

PMID- 11998680
TI  - Nicotinic receptors and hippocampal synaptic plasticity ... it's all in the
      timing.
AB  - As we learn more about the functional expression of nicotinic receptors in
      specific brain regions such as the hippocampus, intriguing interactions are being
      uncovered at the cellular and circuit levels. Recent work from John Dani's
      laboratory provides important insights into how nicotinic receptors can modify
      hippocampal synaptic plasticity in both positive and negative ways, and this
      could help explain the role of nicotinic receptors in learning and memory.

PMID- 11998681
TI  - Glial cell migration directed by axon guidance cues.
AB  - Widespread myelination by oligodendrocytes is essential for the normal
      functioning of the vertebrate CNS. Oligodendrocyte precursors initially arise in
      restricted regions of the neuroepithelium and migrate relatively long distances
      to their final destinations. The signals that guide this migration have remained
      poorly understood, but recent studies suggest that glial precursors use similar
      molecular cues to those that guide axons through the complex terrain of the
      developing CNS. For example, in the developing optic nerve, glial-precursor
      migration from the brain towards the retina is guided by netrin-1 and semaphorin
      3a. These studies suggest a novel mechanism governing glial precursor migration
      and provide new insights into development and the potential to direct CNS injury
      repair.

PMID- 11998682
TI  - Splitting the quantum: regulation of quantal release during vesicle fusion.
AB  - One of the most enduring central hypotheses in neurobiology has been that
      neurotransmission is determined by the quantal release of neurotransmitter. An
      important assumption has been that quantal size (amount of transmitter released
      per vesicle) is constant. Recent work has established that, for dense-core
      granules, quantal size can be varied by stimulation frequency, changes in second
      messenger levels and modification of the proteins of the exocytotic machinery.
      These data argue against the long-held belief in the universality of the quantal
      hypothesis, and raise important but controversial questions as to whether the
      same mechanisms could also regulate release from synaptic vesicles and contribute
      to synaptic plasticity.

PMID- 11998683
TI  - Illuminating cracks in the fragile mind.

PMID- 11998684
TI  - Protein synthesis during LTP: linking synaptic activity to translation.

PMID- 11998685
TI  - EphB and NMDA receptors: components of synaptic plasticity coming together.

PMID- 11998686
TI  - Dynamic depolarization fields in the cerebral cortex.
AB  - Recent physiological evidence shows that in response to stimuli and preceding
      motor activity, large fields of the upper layers of the cerebral cortex
      depolarize. It is argued that this finding is a general one and that these
      dynamic depolarization fields represent the computational elements of the
      cerebral cortex. Each depolarization field engages many more neurons than do
      columns and hyper-columns. These fields can be explained by cooperative neuronal
      computing in layers I-III of the cortex. In these layers, the computing modes
      might be general for all parts of the cerebral cortex and be sufficiently
      flexible to handle all sorts of cortical computations, including perception,
      memory storage, memory retrieval, thought and the production of behavior.

PMID- 11998687
TI  - Rho proteins, mental retardation and the cellular basis of cognition.
AB  - For several decades, it has been known that mental retardation (MR) is associated
      with abnormalities in dendrites and dendritic spines. The recent cloning of seven
      genes that cause nonspecific MR when mutated provides important insights in the
      cellular mechanisms that result in the dendritic abnormalities associated with
      MR. Three of the encoded proteins, oligophrenin 1, PAK3 and alpha PIX, interact
      directly with Rho GTPases. Rho GTPases are key signaling proteins that integrate
      extracellular and intracellular signals to orchestrate coordinated changes in the
      actin cytoskeleton essential for directed neurite outgrowth and the regulation of
      synaptic connectivity. Although many details of the cell biology of Rho signaling
      in the CNS are still unclear, a picture is unfolding showing how mutations that
      alter Rho signaling result in abnormal neuronal connectivity and deficient
      cognitive functioning in humans. Conversely, these findings illuminate the
      cellular mechanisms underlying normal cognitive function.

PMID- 11998688
TI  - Integration of sodium and osmosensory signals in vasopressin neurons.
AB  - Vasopressin (antidiuretic hormone) release has been thought to be controlled by
      interacting osmoreceptors and Na(+)-detectors for > 20 years. Only recently,
      however, have molecular and cellular advances revealed how changes in the
      external concentration of Na+ and osmolality are detected during acute and
      chronic osmotic perturbations. In rat vasopressin-containing neurons, local
      osmosensitivity is conferred by intrinsic stretch-inactivated cation channels and
      by taurine release from surrounding glia. Na+ detection is accomplished by acute
      regulation of the permeability of stretch-inactivated channels and by changes in
      Na+ channel gene expression. These features provide a first glimpse of the
      integrative processes at work in a central osmoregulatory reflex.

PMID- 11998689
TI  - Vesicle pools and short-term synaptic depression: lessons from a large synapse.
AB  - Depletion of a pool of readily releasable vesicles during repetitive presynaptic
      activity is a candidate mechanism for the induction of short-term synaptic
      depression. The large, calyx-type synaptic terminals in the brainstem auditory
      pathway, and especially the calyx of Held, offer unique possibilities for
      studying the cellular mechanisms leading to synaptic depression. Recent work at
      these synapses using presynaptic whole-cell patch-clamp recordings has revealed a
      large pool of readily releasable vesicles. During prolonged presynaptic
      depolarization, vesicles are released in kinetically distinct phases, indicating
      heterogeneity of release probability between vesicles. Heterogeneity might endow
      synapses with a rapid phase of depression at the onset of activity, followed by
      sustained and surprisingly large synaptic strength during the steady-state phase
      of depression. By influencing the synaptic output during repetitive activity,
      vesicle pool dynamics are expected to modulate information processing in neuronal
      networks of the CNS.

PMID- 11998690
TI  - Life span: getting the signal from the nervous system.
AB  - Life span is determined by both environmental and genetic influences. The
      importance of genes is illustrated by the fact that single gene mutations extend
      life span in nematodes, fruit flies and mice. Recent reports reveal that the life
      span of Caenorhabditis elegans is controlled by insulin-like signals from the
      nervous system. Hormones that control life span have recently been identified in
      fruit flies and mice. These findings suggest that neuroendocrine pathways could
      constitute an important determinant of life span across phylogeny. This review
      examines the evidence for nervous system control of longevity and discusses the
      implications for popular models for aging.

PMID- 11998691
TI  - Leonardo da Vinci's contributions to neuroscience.
AB  - Leonardo da Vinci (1452-1519) made far-reaching contributions to many areas of
      science, technology and art. Leonardo's pioneering research into the brain led
      him to discoveries in neuroanatomy (such as those of the frontal sinus and
      meningeal vessels) and neurophysiology (he was the first to pith a frog). His
      injection of hot wax into the brain of an ox provided a cast of the ventricles,
      and represents the first known use of a solidifying medium to define the shape
      and size of an internal body structure. Leonardo developed an original,
      mechanistic model of sensory physiology. He undertook his research with the broad
      goal of providing physical explanations of how the brain processes visual and
      other sensory input, and integrates that information via the soul.

PMID- 11998692
TI  - Expanding the paradigms of placental malaria.

PMID- 11998693
TI  - Entamoeba histolytica Genome Project: an update.

PMID- 11998694
TI  - Unravelling trypanosome antigenic variation mechanisms.

PMID- 11998695
TI  - Clonal theory of parasitic protozoa.

PMID- 11998696
TI  - Ovalocytosis in Papua New Guinea.

PMID- 11998697
TI  - Four aspartic proteases occur in the Plasmodium falciparum food vacuole.

PMID- 11998698
TI  - Benzimidazole binding to Haemonchus contortus tubulin: a question of structure.

PMID- 11998699
TI  - Infective inoculum for Leishmania.

PMID- 11998700
TI  - Hydrogen production in Giardia intestinalis, a eukaryote with no hydrogenosomes.

PMID- 11998701
TI  - Do azoles and chloroquine share similar mechanisms of antimalarial action?

PMID- 11998702
TI  - Do Plasmodium ookinetes invade a specific cell type in the mosquito midgut?
AB  - Recent debate in Plasmodium ookinete invasion has been centered on whether the
      parasite chooses a specific cell type to cross the midgut epithelium in the
      mosquito. A few publications have described the mosquito midgut being composed of
      complex surface-structures, histochemically and biochemically diverse cell types,
      and have proposed that Plasmodium gallinaceum ookinetes prefers a specific cell
      type (Ross cell) in Aedes aegypti for crossing the midgut epithelium. Two recent
      publications reported, however, that with differential interference contrast
      microscopy, all midgut epithelial cells in uninfected mosquitoes appear
      structurally similar and argued that ookinetes do not invade a specific cell
      type. These observations are discussed here in the context of the 'Ross cell'
      hypothesis.

PMID- 11998703
TI  - Alternative insecticides: an urgent need.
AB  - Most insecticides used against pests and vectors of human disease (e.g. fleas,
      flies and mosquitoes) are spin-offs from agrochemical research and development.
      The arsenal of safe and cost-effective public health insecticides is being
      depleted by restrictions for various reasons (e.g. insecticide resistance,
      unacceptable side effects and non re-registration) and the number of new products
      launched is dwindling. Mobilizing public resources and establishment of
      partnerships to support research and development of public health insecticides is
      crucial in the post-DDT and post-pyrethroid era.

PMID- 11998704
TI  - Immunity to Onchocerca spp. in animal hosts.
AB  - This review summarizes research using Onchocerca spp. in chimpanzees, cattle and
      mice to gain insight into the protective immune response to the filarial worm
      Onchocerca volvulus in humans. In addition, Acanthocheilonema viteae has been
      evaluated as a surrogate filarial worm for studying immunity to the infection.
      Immune mechanisms controlling these infections are described and initial success
      using recombinant antigen vaccines in these models is reviewed.

PMID- 11998705
TI  - Emerging Chagas disease in Amazonian Brazil.
AB  - In the Amazon Basin, Trypanosoma cruzi infection is enzootic, involving a variety
      of wild mammals and at least 10 of the 16 reported silvatic triatomine bug
      species. Human cases of Chagas disease are increasing, indicating that the
      disease may be emerging as a wider public health problem in the region: 38 cases
      from 1969 to 1992, and 167 in the past eight years. This article reviews the
      status of Chagas disease in Amazonian Brazil, including known reservoirs and
      vectors, and the genetic diversity of T. cruzi. At least three subspecific groups
      of T. cruzi-T. cruzilZ1, T. cruziZ3 and T. cruziZ3/Z1 ASAT--are present. It
      appears that T. cruzil has an extant capacity for genetic exchange. Attention is
      also drawn to the risk of domestic endemicity, in addition to the tasks facing
      the disease control authorities.

PMID- 11998706
TI  - Trematode life cycles: short is sweet?
AB  - Complex life cycles are a hallmark of parasitic trematodes. In several trematode
      taxa, however, the life cycle is truncated: fewer hosts are used than in a
      typical three-host cycle, with fewer transmission events. Eliminating one host
      from the life cycle can be achieved in at least three different ways. Some
      trematodes show even more extreme forms of life cycle abbreviations, using only a
      mollusc to complete their cycle, with or without sexual reproduction. The
      occurrence of these phenomena among trematode families are reviewed here and show
      that life cycle truncation has evolved independently many times in the phylogeny
      of trematodes. The hypotheses proposed to account for life-cycle truncation, in
      addition to the factors preventing the adoption of shorter cycles by all
      trematodes are also discussed. The study of shorter life cycles offers an
      opportunity to understand the forces shaping the evolution of life cycles in
      general.

PMID- 11998707
TI  - [Are arterial grafts better than venous grafts?].

PMID- 11998708
TI  - [Common computerized medical records and professional secrecy].

PMID- 11998709
TI  - [Keep vision screening of four years old children].

PMID- 11998710
TI  - [Long-term results with the left internal mammary artery as coronary bypass].
AB  - BACKGROUND: From 1986 we have routinely used the left internal mammary artery
      instead of autologous vein as bypass to the left anterior descending coronary
      artery. MATERIAL AND METHODS: A cohort of 52 patients has been followed up for up
      to 12 years. Six years postoperatively, 40 patients were evaluated by clinical
      examination, exercise testing and serum lipid assessment. Of these, 38 underwent
      angiography of the native coronary arteries and of all grafts, which represented
      47 left internal mammary artery, 90 saphenous vein, and 3 right internal mammary
      artery bypasses. Information regarding angina recurrence and the need for
      repeated revascularisation was obtained from hospital records. Twelve-year
      mortality data were provided by public registers. RESULTS: Fifty patients were
      discharged alive. Two serious complications, of which one was fatal, were
      directly related to the use of the left internal mammary artery. After six years,
      all the re-examined patients had improved their exercise tolerance; 25 (63%) were
      angina-free. 44 (94%) left internal mammary artery and 67 (74%) saphenous vein
      bypasses were patent. Tobacco consumption was considerably reduced over the first
      six years postoperatively while mean triglyceride and cholesterol levels remained
      moderately elevated. After 12 years, 18 patients were deceased, half of them from
      coronary heart disease. INTERPRETATION: Our results are in accordance with large,
      international studies.

PMID- 11998711
TI  - [Coronary surgery--arterial grafts instead of venous grafts?].
AB  - BACKGROUND: Recurrence of symptoms and the need for repeat interventions remains
      a clinical challenge following coronary artery bypass surgery, despite excellent
      early results. Saphenous vein graft failure has been identified as a main
      contributing factor to unsatisfactory long-term results. The use of multiple
      arterial grafts instead of venous grafts appears to be a promising treatment
      modality. This article describes our own experience with arterial
      revascularisation and gives a critical review of the literature. MATERIAL AND
      METHODS: Extended arterial revascularisation was performed in 30 patients at our
      institution between 1998 and 2001. Clinical follow-up was performed in all
      patients; re-angiography was done in six patients. 23 patients were operated on
      with bilateral mammary arteries; 11 patients received radial artery grafts.
      RESULTS: The median follow up was 12 months. All patients are alive, none
      suffered a new myocardial infarction. Our results are in accordance with the
      published literature. INTERPRETATION: Arterial grafting is a valuable tool in the
      armamentarium of modern coronary artery bypass surgery. Large randomised trials
      are required to clarify the role of extended arterial grafting in routine
      coronary bypass surgery.

PMID- 11998712
TI  - [Boerhaave's syndrome--an unusual cause of acute retrosternal pain].
AB  - BACKGROUND: Boerhaave's syndrome or spontaneous perforation of the oesophagus is
      a rare condition with a severe prognosis. Adequate treatment is often delayed
      because of misdiagnosis of the condition as cardial, pulmonary or other
      gastrointestinal disease, with a concomitant rise in mortality. MATERIAL AND
      METHODS: A case of Boerhaave's syndrome is described. An 88-year-old male
      presented with acute retrosternal pain, initially believed to be caused by
      cardiac disease. After a delay of more than 24 hours, laparotomy revealed a
      perforation of the oesophagus. RESULTS: The patient was treated with laparotomy,
      drainage, antibiotics, antifungal and medical supportive therapy. Surgical
      closure of the lesion was not performed because of the debilitated state of the
      patient and the delay in diagnosis. He left the hospital in his habitual state
      after 33 days of hospitalization. INTERPRETATION: Boerhaave's syndrome is a
      serious condition that is often misdiagnosed. The preferred treatment is prompt
      surgical closure of the oesophageal defect.

PMID- 11998713
TI  - [Urticaria and angioedema in children].
AB  - BACKGROUND: Urticaria in children is a common disorder often associated with
      angioedema. METHODS: An overview on the pathophysiology, clinical presentation,
      investigation and treatment of urticaria and angioedema in children is presented.
      RESULTS AND INTERPRETATION: Many factors, immunologic and non-immunologic, cause
      histamine release from tissue mast cells and thus contribute to urticaria. Acute
      urticaria may be associated with infections and/or allergy. There is increasing
      evidence that chronic urticaria is an autoimmune disorder caused by functional
      auto-antibodies against IgE and the Fc-receptor on mast cells. Allergy testing
      may be helpful in cases of suspected food or drug allergy where the history is
      not diagnostic. Provocation test for physical urticaria should be performed when
      indicated. Further diagnostic procedures are seldom useful. Non-sedative
      antihistamines are the drugs of choice in urticaria and generally provide
      substantial symptom relief until spontaneous remission occurs.

PMID- 11998714
TI  - [Factors contributing to interindividual variability to chemical toxicity].
AB  - Recognising toxicokinetic and toxicodynamic variability is important in the risk
      assessment of chemicals and may help to explain individual differences in
      susceptibility in exposed populations. This presentation discusses the influence
      of age, gender, disease and genetics on toxicokinetic and toxicodynamic
      processes. Neonates have a reduced capacity for metabolism and elimination of
      xenobiotics that may enhance chemical toxicity caused by a parent chemical.
      Furthermore, the brain, reproductive organs and immune system have critical
      postnatal periods of maturation where they appear highly sensitive to toxic
      effects that interfere with the maturation process and may lead to permanent
      structural or functional organ changes. In the elderly, a combination of reduced
      organ function, disease and use of pharmaceuticals contributes to enhanced
      chemical sensitivity reflected in an increased incidence of adverse drug
      reactions in this population. There is a high degree of functional polymorphism
      in biotransforming enzymes. Such polymorphisms have been shown to contribute to
      interindividual variability in chemical response. During the last few years,
      accounts have been given of several polymorphisms in genes with importance for
      toxicodynamic processes, such as DNA repair genes and receptor genes. However,
      further information is needed in order to evaluate the functional contribution of
      these polymorphisms to chemical sensitivity and health risk.

PMID- 11998715
TI  - [A young, stuporous and afebrile man with icterus and nosebleed].

PMID- 11998716
TI  - [Reverse apheresis--semiautomatic erythrocyte transfusion].

PMID- 11998717
TI  - [Herbs with alleged medical effect].

PMID- 11998718
TI  - [Non-linguistic cognitive symptoms of cerebral stroke].
AB  - BACKGROUND: Cognitive symptoms are common after stroke, but doctors' knowledge
      about such symptoms seems sparse. METHODS: We review the literature and present
      our own clinical experience on selected cognitive losses after stroke. RESULTS
      AND INTERPRETATION: The most common non-linguistic cognitive symptoms are neglect
      (hemi-inattention), visuospatial problems (difficulties in putting elements
      together or to perform spatial tasks), and apraxia (difficulties in performing
      voluntary, purposeful tasks due to mistakes in the choice and order of motor
      elements). More than half of patients suffer from such symptoms in the acute
      phase of stroke and approximately one in four has long-lasting problems.
      Knowledge about these symptoms is essential for effective rehabilitation, good
      information to the patient and his caregivers, and for prognostic purposes. Full
      evaluation of cognitive losses requires a neuropsychological examination, but
      thorough observation of the patient combined with simple pen-and-paper tests can
      be very helpful.

PMID- 11998719
TI  - [Recurrent falls in the elderly].
AB  - BACKGROUND: Approximately 30% of community-dwelling elderly people in developed
      countries fall at least once each year. Although only 10% of falls lead to
      serious injuries, these represent a considerable share of all injury-related
      hospital admissions, with high mortality and morbidity and high health care
      costs. Early detection of persons at risk and effective intervention measures are
      needed. The article gives an overview of current knowledge in this field.
      METHODS: A limited literature search (1989-2001) and a telephone survey among all
      geriatric units in Norway. RESULTS: Recurrent falls are a multifactorial problem
      requiring a multifactorial intervention strategy at any care level and between
      levels. Exercise/balance training and hip protectors seem to be the most
      effective measures in preventing falls and fall injuries. INTERPRETATION:
      Feasible selection criteria, good cooperation routines and knowledge of local
      resources are important. Awareness of the problem is needed not only in
      geriatricians, but all health professionals caring for elderly patients.

PMID- 11998721
TI  - [Treatment by an otopathologist resulted in further ear problems and hearing
      loss].

PMID- 11998720
TI  - [Child health and course of life].

PMID- 11998722
TI  - [Electronic epicrises and electronic medical records].

PMID- 11998723
TI  - [Screening for alloimmune thrombocytopenia].

PMID- 11998724
TI  - [Anticoagulation treatment in atrial fibrillation].

PMID- 11998725
TI  - [PM10 and microparticles].

PMID- 11998726
TI  - [Good intentions--hard realities].

PMID- 11998727
TI  - [Just science?].

PMID- 11998728
TI  - [Acute gallstone pancreatitis].

PMID- 11998729
TI  - [Maternal-infant HIV transmission].

PMID- 11998730
TI  - [Acute gallstone pancreatitis--when should the clearance of biliary tract be
      performed?].
AB  - BACKGROUND: On the basis of a 19-year material we discuss early or delayed
      surgery for definitive clearance of the biliary tract after acute gallstone
      pancreatitis. MATERIAL AND METHODS: During 1980-98, 218 patients, 133 women and
      85 men, median age 69.5 years (16-96 years) with acute gallstone pancreatitis
      were treated at Levanger hospital, Norway. During 1980-89 (period 1), 111
      patients were mainly treated by open operations as soon as the acute pancreatitis
      had settled, while during 1990-98 (period 2), 107 patients were mainly treated
      conservatively and the biliary operations performed
      laparoscopically/endoscopically later. RESULTS: In period 1 two patients died,
      one of them after open surgery (2%). In period 2 four patients died. 21 patients
      were readmitted due to a new attack, two of whom died. Two patients developed
      acute cholecystitis. INTERPRETATION: Early surgery for the gallstone disease in
      patients with acute gallstone pancreatitis is well tolerated, recurrent attacks
      are rare and the mortality low.

PMID- 11998731
TI  - [Secretin stimulated magnetic resonance cholangiopancreatography in diseases of
      the biliary and pancreatic ducts].
AB  - BACKGROUND: MRCP has replaced ERCP as the diagnostic tool in diseases in the
      biliary and pancreatic ducts. Secretin increases the secretion to ducts, and this
      has been reported to improve MRCP image quality. MATERIAL AND METHODS: We report
      our experience with S-MRCP in our first 20 patients. Secretin was given
      intravenously and images were obtained every minute for 10 minutes. These images
      were compared with MRCP images taken before and after secretin stimulation.
      RESULTS: New information was yielded in 18 cases, i.e. information not observed
      in previous radiological examinations. INTERPRETATION: In diagnostics of
      dysfunction of the sphincter of Oddi, the method may be useful, given the
      functional aspect of the procedure where increased pressure in the ducts may lead
      to pain. It may further improve the diagnostics of pancreatic cancer versus
      pancreatitis, in pancreas divisum and sclerosing cholangitis. The method is also
      valuable for clarifying whether there is injury to the pancreatic duct after
      blunt abdominal trauma. Surgical common bile duct injuries may be better assessed
      than with any other method. In difficult pancreatic and biliary investigations, S
      MRCP seems to be a useful and complication-free supplement to existing diagnostic
      methods.

PMID- 11998732
TI  - [Genetic analysis of Mycobacterium tuberculosis in Norway 1994-98].
AB  - BACKGROUND: This study was undertaken to determine the genetic diversity in the
      population of Mycobacterium tuberculosis in Norway and to detect the degree of
      transmission between patients. The quality of the culturing work was ascertained
      by analysing the data for possible cross-contamination. MATERIAL AND METHODS:
      Genotypic relationships among 92% of all strains isolated in Norway in 1994-98
      were assessed using IS6110-restriction fragment length polymorphism analysis. The
      strains had been isolated from 717 different patients. For isolates with less
      than five copies of IS6110 the directly repetitive element was also used.
      RESULTS: 20 isolates (2.8%) represented false positive samples. The isolates from
      14.5% of the native Norwegian patients and 19.7% of the foreign patients were
      part of one of 35 clusters. INTERPRETATION: The results indicate that the degree
      of recent transmission of tuberculosis in Norway was low and that transmission
      between immigrants and native Norwegians was uncommon. The majority of cases were
      due to reactivation of previous disease.

PMID- 11998733
TI  - [A patient with periodontitis, oral candidiasis and undiagnosed HIV infection].
AB  - BACKGROUND: HIV infection may be associated with necrotic periodontal disease,
      oral candidiasis and idiopathic thrombocytopenic purpura. MATERIAL, METHODS AND
      RESULTS: A 38-year-old man with necrotic periodontal disease and oral candidiasis
      was referred to the Department of Periodontology, University of Oslo. With a
      diagnosis of idiopathic thrombocytopenic purpura he received immunosuppressive
      medication and had been splenectomized without any improvement. He was referred
      for HIV testing and diagnosed as HIV positive. Antiviral therapy restored his low
      platelet counts and increased the numbers of CD4 and CD8 positive cells in
      peripheral blood. Antifungal treatment with mycostatin and debridement of the
      teeth combined with metronidazole was effective. The patient has had no
      recurrence of oral candidiasis, and the periodontal conditions have been stable
      during the follow-up. INTERPRETATION: Dentists and physicians should be familiar
      with the most frequently occurring oral symptoms of HIV infection.

PMID- 11998734
TI  - [HIV infection in pregnant women--clinical findings and treatment].
AB  - BACKGROUND AND METHODS: The paper reviews HIV infection in pregnancy. We have
      mainly used PubMed for literature searches with focus on risk factors for
      vertical infection and measures to prevent mother-to-child transmission. RESULTS:
      The risk of vertical HIV-transmission is greatest when the mother has high levels
      of viraemia. Antiviral treatment decreases the fetal risk. When the viral load is
      low, i.e. HIV-RNA below 1000 copies/ml, the risk of infection of the fetus is
      small; individually adapted antiviral treatment is indicated to obtain this goal.
      Increased risk of infection of the fetus may occur as a result of vaginal
      bleeding, amniocentesis, vaginal delivery, the use of scalp electrodes and fetal
      scalp pH measurement. The use of vacuum extraction and forceps delivery should be
      avoided if possible. An important factor associated with increased fetal risk is
      long lasting rupture of the membranes (> 4 hours). INTERPRETATION: Elective
      delivery by Caesarean section at 38th week, before labour and rupture of the
      membranes, is advocated. A Caesarean section may, however, cause complications,
      and vaginal delivery at term may be considered when the viraemia is low (HIV-RNA
      < 1000 copies/ml). Amniotomy and long-standing rupture of the membranes should be
      avoided, as should breastfeeding.

PMID- 11998735
TI  - [The discovery of the leprosy bacillus].
AB  - Gerhard Henrik Armauer Hansen (1841-1912) worked on leprosy throughout his
      career. Following his discovery of the leprosy bacillus in 1873, he proposed
      legislation that, when enacted in 1877 and 1885, established preventive measures
      aimed at isolating infectious patients. Around 1920, leprosy was more or less
      eradicated in Norway after a period of decline starting in 1850. Over this
      period, more than 8,000 cases were registered. Armauer Hansen's unique research
      achievement was based on a scientific and medical infrastructure in place long
      before he started his work. This context had several implications, though the
      discovery of the leprosy bacillus holds a particular fascination, with bearings
      on the interaction between medicine and the community even today.

PMID- 11998736
TI  - [Diagnostic imaging techniques in the investigation of dementia].
AB  - BACKGROUND: Neuroimaging can provide valuable information in the diagnostic work
      up of patients presenting with suspected dementia. MATERIAL AND METHODS: Based on
      our experience from a memory clinic at Ulleval University Hospital in Oslo,
      Norway and on relevant literature identified on Medline, we give an overview of
      the use of neuroimaging methods in patients with suspected dementia. RESULTS AND
      INTERPRETATION: CT of the brain should be offered to all patients with suspected
      dementia as CT can provide essential diagnostic information regarding focal
      cerebral pathology (tumour, haemorrhage, normal pressure hydrocephalus). A CT
      scan is of no value in the diagnostic evaluation of patients with mild to
      moderate Alzheimer's disease as age-related atrophy may be a confounding factor.
      CT is necessary to reveal infarcts when vascular dementia is suspected, but lacks
      sensitivity in the detection of diffuse cerebrovascular disease. MRI is
      recommended in younger patients and may be used to diagnose subcortical lesions,
      e.g. leukoariosis. The accuracy of SPECT in the assessment of patients with
      cognitive impairment is not yet established though it seems to be a promising
      method for the detection of frontotemporal dementia. Functional MR may play a
      role in the work-up of dementia in the future.

PMID- 11998737
TI  - [Accidental hypothermia in the elderly].
AB  - BACKGROUND: Accidental hypothermia is unintended body core temperature of 35
      degrees C or below, a known hazard to elderly people in temperate and cold
      climates. MATERIAL AND METHODS: We present two old patients with severe
      hypothermia and a review of the literature focusing on risk factors, clinical
      presentation, and the treatment of hypothermia in the elderly. RESULTS: Two
      patients, aged 90 and 102 years, with body core temperature < 28 degrees C were
      successfully treated at Ulleval University Hospital, Oslo, Norway with slow
      active external rewarming and a low stress strategy as recommended in the
      geriatric literature. Successful treatment with more rapid rewarming and use of
      internal rewarming like peritoneal lavage has also been published. The prognosis
      of elderly victims of hypothermia is known to be worse than for younger
      individuals. Epidemiological data are scanty. The most important risk factors are
      connected to ageing itself and to the morbidity often found in elderly
      hypothermia victims. Treatment is based on experience from few cases, minor
      prospective studies mainly on rewarming of younger patients and clinical
      experience from younger patients. INTERPRETATION: There is a need for more
      knowledge and experience of treating elderly hypothermia victims.

PMID- 11998738
TI  - [Evaluation of methods in the treatment of lumbar disk prolapse with root
      avulsion].

PMID- 11998739
TI  - [Medicine based on information technology--effect on autonomy and vulnerability].

PMID- 11998740
TI  - [My troubled heart].

PMID- 11998741
TI  - [Selective serotonin reuptake inhibitors--adverse effects not documented?].

PMID- 11998742
TI  - [Epicrisis automatically to the patient, too? Yes!].

PMID- 11998743
TI  - [Rescue helicopter service in Bodo].

PMID- 11998744
TI  - [Emergency service--is the quality good enough?].

PMID- 11998745
TI  - The structure of the coherent alpha-rhythm of the electroencephalogram of the
      frontal cortical areas in healthy human subjects and patients with mental
      pathologies.

PMID- 11998746
TI  - Role of cyclic nucleotides in mediating the nitric oxide (II) effects on
      transmitter release and the electrogenesis of motor nerve endings.

PMID- 11998747
TI  - Serotonin-dependent resubordination of the respiratory rhythm to the central
      pattern generator of cyclic locomotion in the pulmonate mollusk Lymnaea.

PMID- 11998748
TI  - Biodiversity protection and quality of water: the role of feedbacks in
      ecosystems.

PMID- 11998749
TI  - Peculiarities of the structure of the tarso-metatarsal joints in primate foot and
      the origin of its grasping ability.

PMID- 11998750
TI  - Relative effects of soil and surface air on mammal burrow temperature: a study of
      the bobac burrow as an example.

PMID- 11998751
TI  - An optimization model of the photosynthetic leaf: the model of optimal
      photosynthetic CO2 fixation within leaves of mesophytic C3 plants.

PMID- 11998752
TI  - Structural and functional adaptations of the sable digestive tract to plant food.

PMID- 11998753
TI  - The structure of the cuticle of guard hair in fruit-eating bats (Chiroptera,
      Pteropodidae).

PMID- 11998754
TI  - The jaw apparatus of the heteromorphic ammonite Australiceras whitehouse, 1926
      (Mollusca: Cephalopoda) from the Aptian of the Volga region.

PMID- 11998755
TI  - Diagnostics of the optimum temperatures for photosynthesis by measuring
      chlorophyll fluorescence in plants.

PMID- 11998756
TI  - Immunocytochemical analysis of Acoela sperms as an approach to understanding the
      phylogenetic position of this group.

PMID- 11998757
TI  - Neural critical bands and inhibition in the auditory midbrain of the house mouse
      (Mus domesticus).

PMID- 11998758
TI  - Characteristic features of the vertebral column development in Hynobiidae
      (Caudata).

PMID- 11998759
TI  - Apoptosis as potato defense response against ring-rot disease.

PMID- 11998760
TI  - Effect of pulsed laser radiation on regeneration of injured muscles with
      different regeneration capacities and the state of the thymus.

PMID- 11998761
TI  - Factors affecting the cloning efficiency of fibroblasts colonies in human bone
      marrow cultures.

PMID- 11998762
TI  - Characteristics of the plasma membrane Cl(-)-ATPase of the bream (Abramis brama)
      brain sensitive to the inhibitory receptor ligands.

PMID- 11998763
TI  - Birth plans and professional autonomy.

PMID- 11998764
TI  - Moral attitudes & mental disorders.
AB  - When psychiatrists treat patients with mental disorders--when clinicians of any
      stripe have a "difficult patient"--they confront and must come to terms with the
      thought that the patient is morally responsible for his conduct. Taken to its
      extreme form, this attitude leads to a repudiation of the whole concept of mental
      illness. In a modest form, and held perpetually in tension with an objective,
      clinical stance toward mental disorders, it is an ineluctable part of the
      practice of psychiatry.

PMID- 11998765
TI  - Individual responsibility for health. Decision, not discovery.
AB  - Health policy sometimes hinges on claims about the responsibility borne by people
      or corporations for health outcomes. We don't want these claims to be arbitrary,
      so we construe them as discoveries of plain fact. But we're mistaken. They are
      interwoven with our values and social institutions. Recognizing that they are
      allows us to debate them more honestly and thoroughly.

PMID- 11998766
TI  - Eternal mysteries, right here.

PMID- 11998767
TI  - Health care reform: still possible.
AB  - Now might be the time, if the proposal is crafted right.

PMID- 11998768
TI  - Rationing: don't give up.
AB  - It's not only necessary, but possible, if the public can be educated.

PMID- 11998769
TI  - Unintended messages: the ethics of teaching genetic dilemmas.
AB  - Bioethicists teaching and writing about the uses of prenatal genetic testing
      sometimes use "difficult cases" in which people with a disability want to test
      and select for the presence of their disability. Such cases challenge our
      stereotypes but also play into them.

PMID- 11998770
TI  - Is suffering the enemy?
AB  - The relief of suffering is the great goal of medicine. That physicians give up on
      suffering when they can do nothing about the underlying condition is one of the
      contemporary criticisms of medicine. Yet even in irremediable suffering there is
      something noble, to which physicians should attend.

PMID- 11998771
TI  - The boundaries of identity.

PMID- 11998772
TI  - The ethics of multiple vital organ transplants.

PMID- 11998773
TI  - "Tuskegee revisited" revisited.

PMID- 11998774
TI  - Sex selection: final word from the ASRM Ethics Committee on the use of PGD.

PMID- 11998775
TI  - Canada announces restrictions on publicly funded stem cell research.

PMID- 11998776
TI  - The cloned pigs and the "reality" of xenotransplantation.

PMID- 11998777
TI  - Aid to fetuses with dependent mothers.

PMID- 11998778
TI  - Law and ethics in a public health emergency.

PMID- 11998779
TI  - Anaemia in persons with HIV infection: prognostic marker and contributor to
      morbidity.
AB  - Human immunodeficiency virus (HIV)-infected patients experience a range of
      haematological complications including anaemia, neutropenia, lymphopenia and
      thrombocytopenia. Anaemia is a prognostic marker of future disease progression or
      death, independent of CD4 and viral load. Recovery from anaemia reduces the risk
      of disease progression to approximately the same level as seen among patients who
      have never had anaemia. Additionally, anaemia impacts a range of dimensions of
      quality of life, most commonly through fatigue. Anaemia can be caused by a range
      of mechanisms including infections, neoplasms, dietary deficiencies, blood loss
      and medication. Histologically, bone marrow hypoproliferation and dysplasia are
      the most commonly seen. Both AZT and d4T induce macrocytosis, however, AZT, but
      not d4T, has broader myelosuppressive effects both in vitro and in vivo. The
      management of anaemia typically includes correction of the underlying cause(s)
      and blood transfusion or erythropoietin. However, blood transfusions and iron
      supplementation may activate HIV expression and possibly worsen
      immunosuppression. Recombinant human erythropoietin (rHuEPO) is an effective
      means of improving haemoglobin and reducing transfusion requirements in patients
      who have low (< 500 IU/L) endogenous erythropoietin levels.

PMID- 11998780
TI  - Pediatric HIV-1 infection: advances and remaining challenges.
AB  - HIV-1 infection is one of the leading causes of childhood morbidity and mortality
      globally and mother-to-child transmission (MTCT) is the major mode of infection.
      Over the past decade, natural history and interventional studies have improved
      our understanding of the pathogenesis of MTCT and pediatric HIV-1 infection. This
      has resulted in the development of effective preventive strategies to reduce new
      infections and therapeutic strategies to improve outcome following infection.
      However, successful implementation of these preventive and therapeutic strategies
      has been limited in resource-poor settings, where the majority of new pediatric
      infections occur. In addition, toxicities and antiretroviral resistance may limit
      the long-term utility of currently available strategies. Continued efforts to
      understand MTCT and pediatric HIV-1 pathogenesis and to refine preventive and
      therapeutic strategies are of high priority.

PMID- 11998781
TI  - Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects.
AB  - Shared epidemiological risks have resulted in HIV-infected populations having a
      high prevalence of hepatitis B virus (HBV) co-infection. Several prospective
      studies have investigated the impact of HBV co-infection on HIV disease
      progression; most of them were negative. On the contrary, there is evidence that
      HIV may modify the natural history of HBV infection. HIV positive subjects have
      higher rates of HBV chronification, higher HBV replication, lower ALT levels and
      lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co
      infection on the outcome of HBV infection is still controversial, even if some
      studies have shown an accelerated progression towards decompensated cirrhosis in
      HIV co-infected subjects. HBV co-infection is a risk factor for severe
      hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV
      subjects, however its efficacy in immunosuppressed patients is still
      controversial. HIV co-infection decreases the effectiveness of Interferon in the
      treatment of HBV infection. Because of its activity against both HBV and HIV,
      lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and
      as part of an antiretroviral regimen, but the rate of sustained response is poor
      and HBV strains with mutations associated with lamivudine resistance occur at a
      rate of 20% per year. Trials of new drugs with activity against HBV, some of them
      with activity also against HIV, and some of them without cross-resistance with
      lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will
      probably soon come of age.

PMID- 11998782
TI  - Antiretroviral resistance testing for clinical management.
AB  - The advent of highly active antiretroviral therapy (HAART) has dramatically
      changed the management of HIV disease. These powerful regimens of drugs have
      reduced morbidity and mortality as well as number of hospitalizations among
      individuals with HIV. Nevertheless, many patients fail to achieve viral
      suppression. Various factors underlie this problem, but resistance to current
      medications has been increasingly recognized as an important element. Several
      methods of assessing antiretroviral resistance in HIV-1 are currently available.
      Phenotype assays directly assess the level of susceptibility of a virus to
      specific drugs. Genotype assays determine the presence of viral mutations that
      may affect viral susceptibility to a particular drug or class of drugs. An
      increasing amount of data indicates that antiretroviral resistance testing may
      improve response to therapy and increase the likelihood of achieving viral
      suppression. In this paper we review the available data regarding the role of
      antiretroviral resistance testing and compare the two different assays. We also
      discuss limitations of the current assays, interpretation of the data, and
      current consensus guidelines. Although many questions remain, antiretroviral
      resistance testing along with expert opinion can aid in the management of HIV
      disease.

PMID- 11998783
TI  - The potential role of interleukin-2 in patients with HIV infection.
AB  - Interleukin-2 (IL-2) is a T cell derived cytokine that leads to a sustained
      expansion of the CD4+ T cell pool when given as 5-day cycles approximately every
      8 weeks. An extensive series of phase I/II studies have been carried out and have
      leaded to the initiation of two phase III trials that are currently enrolling
      patients in 23 countries. Studies of the mechanisms of action have revealed that
      IL-2 is capable of inducing the polyclonal proliferation of CD4+ and CD8+ T
      cells, even in the absence of expression of the high affinity IL-2 receptor.
      While IL-2 leads to a 6-fold increase in T cell proliferation and a 2-fold
      increase in T cell death, the primary mechanism of action leading to expansion of
      the CD4+ T cell pool appears to be an increase in CD4+ T cell survival. While
      early work focused on the ability of IL-2 to exert these effects in patients with
      relatively early stages of HIV infection, more recent work, in the setting of
      HAART, indicates that these effects may be seen at all stages of HIV disease. The
      results of the phase III studies should provide an answer to the question of
      whether or not this is a strategy that will be of clinical benefit.

PMID- 11998785
TI  - Association of Chairs of Departments of Physiology. 2001 survey results.

PMID- 11998784
TI  - The role of Tat in HIV-1 replication: an activator and/or a suppressor?
AB  - Tat is a key trans-activator of HIV-1 gene transcription and major progress has
      been accomplished in recent years in regard to understanding its mechanism of
      action. An important breakthrough was the identification of the TAR-Tat-Cyclin
      (Cyc) T1-Cyclin-dependent kinase 9 (CDK9) complex, in which CDK9 can
      hyperphosphorylate the carboxyl-terminus domain (CTD) of the RNA polymerase
      (RNAP) II complex. A different activity of Tat has recently been identified in
      reverse transcription. Notably, mutated HIV-1 that lacks a functional Tat protein
      cannot efficiently generate reverse transcription products following infection of
      permissive cells. Furthermore, Tat can also inhibit reverse transcriptase
      activity in cell-free assays and can act as a suppressor of reverse transcription
      at late stages in the viral life cycle. This suppressor activity of Tat can
      restrict the premature reverse transcription of viral RNA in the cytoplasm and
      allows the viral genome to be packaged as intact RNA molecules.

PMID- 11998786
TI  - Should nurses serve as medical care 'gatekeepers'?

PMID- 11998787
TI  - Failure to chart name of Dr. & time catheter in. Case on point: Oliver v.
      Woodward, 2001 WL 1591133 So.2d -AL.

PMID- 11998788
TI  - KS: suspended nurse is ordered reinstated: court refuses to award back pay to
      nurse.

PMID- 11998789
TI  - AL: conviction results in license revocation: suspension after violation of
      reinstatement terms.

PMID- 11998790
TI  - Suspension is penalty for 'playing games with chart'. Case on point: in re Civil
      Serv. Emps. Local v. Tioga County (No. 89654 N.Y. App. Div.) -NY.

PMID- 11998791
TI  - Getting along better with others.

PMID- 11998792
TI  - Amendments to the Bloodborne Pathogens Standard Needlestick Safety and revised
      recordkeeping rules.

PMID- 11998793
TI  - Experimental nonsurgical tattoo removal in a guinea pig model with topical
      imiquimod and tretinoin.
AB  - BACKGROUND: Tattoo removal is a common request in dermatologic surgery practices.
      Conventional tattoo removal modalities consist of mechanical, chemical, and
      thermal methods, but these interventions may result in undesirable dermal damage,
      disfiguring scars, and pigmentary changes. OBJECTIVE: To evaluate the efficacy of
      topical imiquimod and tretinoin for the removal of tattoos in a guinea pig model.
      METHODS: Five albino guinea pigs (A-E) were tattooed with black, red, green, and
      yellow. Beginning 6 hours after tattooing, A received no treatment, B was treated
      with petrolatum, C had imiquimod cream alternating with tretinoin gel, D had
      imiquimod cream alone, and E received tretinoin gel alone. The animals were
      treated for 7 days. Biopsies of the tattoos were taken at 6 hours, 7 days, and 28
      days. RESULTS: Control guinea pig B had normal-appearing tattoos with consistent
      histopathology on day 28. Guinea pig D, treated with imiquimod cream clinically,
      had no visible tattoo, consistent with greatly diminished or no dye evident on
      histopathology. Guinea pig E, treated with tretinoin gel, and guinea pig C,
      treated with combination tretinoin gel and imiquimod cream, had faded tattoos and
      moderate clearance of pigment on histopathology. CONCLUSION: In the guinea pig,
      the use of imiquimod was successful as a nonsurgical method of acute-phase tattoo
      removal, but was associated with fibrosis and the loss of dermal appendages.

PMID- 11998794
TI  - Epstein-Barr virus-associated lymphoma in a child undergoing an autologous stem
      cell rescue.
AB  - Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a serious
      disorder seen in various states of immunodeficiency, often with a fatal outcome.
      In this article, a patient with EBV-lymphoma after autologous stem cell rescue
      for treatment of a nonhematologic solid tumor is described. The child, a 4-year
      old boy, had unilateral retinoblastoma with metastatic spread to the central
      nervous system. He had previously received both local tumor bed and craniospinal
      radiation therapy together with intensive myeloablative alkylator chemotherapy
      before autologous stem cell rescue. Histologically confirmed lymphoma with
      evidence of active EBV proliferation developed within cervical lymph nodes 3
      weeks after his first autologous stem cell rescue. A complete clinical remission
      of the lymphadenopathy was obtained after infusions of rituximab (an anti-CD20
      monoclonal antibody), acyclovir, and high-titer anticytomegalovirus
      immunoglobulin. The patient died approximately 6 months later of persistent and
      progressive retinoblastoma without any clinical evidence of lymphoma. It is
      concluded that EBV-LPD should be included in the differential diagnosis in
      patients in whom lymphadenopathy develops after autologous stem cell rescue.

PMID- 11998795
TI  - Introduction to orthodontics to a full-service dental laboratory, Part II.
      Fabrication of a space maintainer.

PMID- 11998799
TI  - PRESERVE trial surprises with unexpected results on LV hypertrophy reduction with
      calcium channel blockers.

PMID- 11998800
TI  - AstraZeneca's investment in landmark trials in heart failure.

PMID- 11998801
TI  - Aspirin and deep vein thrombosis.

PMID- 11998802
TI  - Multi-centre trial of aprotinin [correction of aspirin] highlights increased
      safety with higher dose.

PMID- 11998803
TI  - Implementing community-directed treatment with ivermectin for the control of
      onchocerciasis in Uganda (1997-2000): an evaluation.
AB  - Over the period 1997-2000, an evaluation was made, in 10 districts of Uganda, of
      the onchocerciasis-control programme based on community-directed treatment with
      ivermectin (CDTI). This programme is supported by the Ministry of Health, the
      African Progamme for Onchocerciasis Control (APOC) and The Carter Center Global
      2000 River Blindness Programme. The data analysed came from: (1) monthly and
      annual reports; (2) annual interviews, in randomly-selected communities in
      selected districts, with heads of household, community leaders and ivermectin
      distributors; (3) participatory evaluation meetings (PEM); (4) participant
      observation studies; and (5) key informants. The percentage of treated
      communities in the 10 study districts achieving satisfactory treatment coverage
      [i.e. > or = 90% of the annual treatment objective (ATO)] rose from 46.0 in 1997
      to 86.8 in 2000. This improvement was largely attributable to the adoption of
      collective CDTI decision-making by community members, avoidance of paving
      monetary incentives to the ivermectin distributors, and the satisfaction with the
      programme of those who had been treated. Coverage improved as the numbers of
      community members who were involved in choosing the method of distribution and in
      selecting their own community-directed health workers (CDHW) increased. Health
      education was also critical in improving individual members' involvement in
      decision-making, and in mobilizing other community members to take part in CDTI.
      Involvement of kinship groups, as well as educated community members as
      supervisors of CDHW, also helped to increase coverage. In a regression model,
      satisfaction with the programme was revealed as a significant predictor of the
      achievement of the target coverage (P<0.001). Cost per person, as an indicator
      for sustainability, varied with the size of the population under treatment, from
      at least U.S. $0.40 when the district ATO was <15,000 people, to U.S. $0.26 with
      an ATO of 15,000-40,000 and less than U.S. $0.10 when the district ATO exceeded
      40,000 people. These results cast doubt on the validity of the current APOC
      indicator for sustainability, of a cost of no more than U.S. $0.20/person for all
      CDTI projects, whatever the size of the population to be treated. Although some
      women were involved in decision-making, their current involvement as supervisors
      or CDHW was minimal. Most of the present data were obtained through monitoring
      and operational-research activities that have been carried out, in an integrated
      fashion, within the Ugandan CDTI programme since its launch. It is recommended
      that assessment, monitoring and evaluation be widely used within all CDTI
      efforts. Operational research should remain focused and appropriate and directly
      involve the personnel who are executing the programme.

PMID- 11998804
TI  - Sharing experience to make a real difference.

PMID- 11998805
TI  - It's our duty to stop racism.

PMID- 11998806
TI  - When should notes be countersigned?

PMID- 11998807
TI  - I owe it to my wife to reject the old regime.

PMID- 11998808
TI  - Don't look now--there's a new leader.

PMID- 11998809
TI  - Effects of heparin and lisofylline on pulmonary function after smoke inhalation
      injury in an ovine model.
AB  - OBJECTIVE: This study evaluates the effects of heparin alone and in combination
      with lisofylline, 1-(5-R-hydroxyhexyl)3,7-dimethylxanthine, on severe smoke
      injury. DESIGN: Prospective animal study with concurrent controls. SETTING: An
      animal laboratory. SUBJECTS: Eighteen 1-yr-old female sheep, weighing 24-32 kg.
      INTERVENTIONS: After smoke exposure and tracheostomy, animals were divided into
      three groups. Group S (n = 6) received nebulized saline through an endotracheal
      tube every 4 hrs for 48 hrs. Group H (n = 6) received 10,000 units of nebulized
      heparin every 4 hrs. Group LH (n = 6) was treated with nebulized heparin and
      intravenous infusion of lisofylline (10 mg x kg(-1) x hr(-1)) for 48 hrs after a
      bolus injection (20 mg/kg). Animals initially breathed room air spontaneously. If
      PaO2 was <50 torr and PaCO2 >60 torr, animals were mechanically ventilated. Sheep
      were killed 48 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Blood gases were
      measured serially. At 48 hrs, ventilation perfusion distribution mismatching was
      analyzed by using the multiple inert gas elimination technique. Lung
      malondialdehyde was determined. The postinjury increase in alveolar-arterial
      oxygen tension gradient (LH, 36.7 +/- 3.5 vs. S, 89.0 +/- 24.6 torr at 48 hrs)
      was significantly attenuated in those animals receiving LH. The percentage of
      pulmonary shunt, Qs/Qt (LH, 20.8 +/- 4.9 vs. S, 36.6 +/- 4.6%), and the
      percentage of animals that required ventilation (LH, 0 vs. S, 67%) were
      significantly reduced in LH. Multiple inert gas elimination technique study
      showed that the true shunt fraction was decreased in LH. Lung malondialdehyde was
      significantly less in LH (LH, 0.33 +/- 0.06 vs. S, 0.56 +/- 0.09 nmol/mg
      protein). There was no significant difference in any of these variables between H
      and S. CONCLUSION: Treatment with heparin alone did not attenuate pulmonary
      dysfunction after severe smoke injury. Combined treatment with nebulized heparin
      and systemic lisofylline had beneficial effects on pulmonary function in
      association with a decrease in blood flow to poorly ventilated areas and less
      lipid peroxidation.

PMID- 11998812
TI  - Risk assessment. Genes express dissatisfaction with environment.

PMID- 11998813
TI  - Natural history of traumatic rupture of the thoracic aorta managed
      nonoperatively: a longitudinal analysis.
AB  - BACKGROUND: Although traumatic rupture of the thoracic aorta (TRA) has
      traditionally been considered a surgical emergency, there exists a small patient
      population for whom nonoperative management may be appropriate. The short- and
      long-term consequences of patients managed in a nonoperative fashion remain
      unclear. METHODS: A review of patients admitted with TRA over a period of 16
      years was performed. Patients who did not undergo operative repair within 24
      hours of injury and diagnosis comprised the study group. RESULTS: One hundred
      forty-five patients were admitted with TRA. Of these, 30 underwent a period of
      nonoperative management. The mean age of the study patients was 44 +/- 21 years,
      80% were male, and the mean Injury Severity Score (ISS) was 34 +/- 9. Fifteen
      patients underwent delayed operation (DELAY group) at more than 24 hours after
      injury and diagnosis and 15 patients never underwent repair (NON-OP group). The
      median time to operation in the DELAY group was 3 days (range 2 to 90). Three
      patients exhibited progression of TRA within 5 days of injury and of these, 2
      died. A total of 3 deaths occurred in the DELAY group (1 rupture and 2
      intraoperative arrests). The fifteen NON-OP patients were significantly older
      (mean age 52 +/- 22 versus 36 +/- 18 years; p = 0.03), tended to be more severely
      injured (mean ISS 36 +/- 9 versus 32 +/- 8; p = 0.2), and had more premorbid risk
      factors than the DELAY patients. Five NON-OP patients died, all because of severe
      head injuries. On long-term follow-up of NON-OP patients, all 10 survivors are
      alive at a median of 2.5 years (range 6 months to 5 years) without progression of
      injury or the need for operation. Five of the 10 had complete radiographic
      resolution of their injuries and 5 have asymptomatic and radiographically stable
      pseudoaneurysms. CONCLUSIONS: Selected patients with multiple severe associated
      injuries or high-risk premorbid conditions may have their operations for TRA
      delayed temporarily or even indefinitely with acceptable survival rates. The
      potential for rapid progression of TRA in the same patients, however, mandates
      serial radiographic examinations during the first week of hospitalization after
      injury and diagnosis.

PMID- 11998814
TI  - Protective effects of protein kinase C during myocardial ischemia require
      activation of phosphatidyl-inositol specific phospholipase C.
AB  - BACKGROUND: Protein kinase C (PKC) activation during myocardial ischemia is
      thought to be cardioprotective. However, the mechanism of ischemia-induced PKC
      activation remains unclear. We hypothesized that ischemic PKC activation occurs
      through activation of phosphatidyl-inositol specific phospholipase C (PI-PLC) and
      protects the heart from ischemic injury. METHODS: Isolated rabbit hearts were
      subjected to 20 minutes of normothermic ischemia and reperfusion. The PI-PLC
      inhibitor U73122 (0.5 micromol/L), its inactive analogue U73343 (0.5 micromol/L),
      or the PKC inhibitor chelerythrine (2 micromol/L) were given just before
      ischemia. Another group received U73122 plus the direct PKC activator phorbol 12
      myristate-13-acetate (PMA, 10 pmol/L). Measurements included contractile
      function, intracellular calcium, PI-PLC activity, and translocation of PKC
      isoforms. RESULTS: PI-PLC activity increased during myocardial ischemia and was
      inhibited by U73122. PI-PLC inhibition prevented the ischemic translocation of
      PKC-alpha, PKC-epsilon, and PKC-eta, and impaired cardiac recovery and cytosolic
      calcium regulation without significant changes in energy metabolism. PMA restored
      both contractile function and PKC translocation pattern in U73122-treated hearts.
      Direct PKC inhibition with chelerythrine mimicked the effects of U73122.
      CONCLUSIONS: PI-PLC mediates PKC translocation during myocardial ischemia.
      Inhibition of PI-PLC or PKC activation, or both, during ischemia significantly
      impairs postischemic myocardial recovery.

PMID- 11998815
TI  - Glucose-insulin-potassium infusion for myocardial protection during off-pump
      coronary artery surgery.
AB  - BACKGROUND: The purpose of this randomized, double-blind, placebo-controlled
      pilot study was to determine the effectiveness of an intravenous glucose-insulin
      potassium (GIK) infusion in preventing myocardial damage and maintaining cardiac
      performance in patients undergoing "off-pump" myocardial revascularization.
      METHODS: Forty-six adult patients undergoing elective off-pump coronary artery
      bypass received either normal saline or a GIK infusion immediately after the
      induction of anesthesia through the first 12 hours of intensive care unit
      convalescence. Measurements of blood glucose, circulating creatine kinase MB and
      troponin I concentrations, as well as cardiac index (CI) and mixed venous oxygen
      saturation (SvO2), were obtained immediately before starting the infusion
      (baseline) and at 6, 12, and 24 hours post-initial coronary artery occlusion.
      RESULTS: Five patients (8%) requiring cardiopulmonary bypass were excluded from
      data analysis. Twenty patients received saline. Twenty-one received GIK. Blood
      glucose was significantly higher in the GIK group. The concentration of
      circulating creatine kinase MB and troponin I significantly increased over time
      after off-pump coronary artery bypass, with no significant intergroup
      differences. Cardiac index and SvO2 did not differ significantly between groups.
      CONCLUSIONS: A GIK infusion protocol commonly used as an adjunct to reperfusion
      therapy for acute myocardial infarction causes insulin-resistant hyperglycemia in
      elective off-pump coronary artery bypass patients with no demonstrable benefit.
      The finding of significant release of cardio-specific enzymes in individual
      patients implies an ongoing need to develop more effective strategies for
      myocardial protection during off-pump coronary artery bypass.

PMID- 11998816
TI  - Effects of in vivo myocardial ischemia and reperfusion on interstitial nitric
      oxide metabolites.
AB  - BACKGROUND: There have been numerous studies examining the role of nitric oxide
      (NO) in myocardial ischemia-reperfusion injury; however, few studies have
      included measurements of NO or related reactive nitrogen species. The purpose of
      this study was to determine the effects of in vivo regional myocardial ischemia
      on interstitial fluid (ISF) reactive nitrogen species. METHODS: Open chest pigs
      were submitted to one of three protocols: (1) 15 minutes coronary occlusion and 2
      hours reperfusion, (2) 60 minutes coronary occlusion and 2 hours reperfusion, or
      (3) two-cycle ischemic preconditioning (IPC) followed by prolonged ischemia and 2
      hours reperfusion. The stable NO metabolites, nitrite plus nitrate (NOx), in
      cardiac microdialysis samples were measured by ozone chemiluminescence. RESULTS:
      NOx concentration decreased 40% +/- 6% (p < 0.05) during brief ischemia but
      returned to baseline during reperfusion. Dialysate NOx levels decreased further
      after 60 minutes ischemia (60% +/- 3% of baseline, p < 0.01) but reperfusion
      dialysate NOx concentration increased 34% +/- 9% above baseline (p < 0.05).
      Preconditioning did not increase dialysate NOx but did accelerate the ischemia
      induced decrease in NOx levels (p < 0.05). Reperfusion NOx levels in
      preconditioned pigs were significantly lower than in nonpreconditioned pigs (p <
      0.05). CONCLUSIONS: These results suggest that ischemia is associated with
      decreased ISF NOx concentration. Reperfusion NOx levels are increased after
      prolonged ischemia, an effect that is significantly blunted by ischemic
      preconditioning.

PMID- 11998817
TI  - Aortic arch advancement: the optimal one-stage approach for surgical management
      of neonatal coarctation with arch hypoplasia.
AB  - BACKGROUND: The optimal surgical treatment for neonatal coarctation with aortic
      arch hypoplasia (NCoAo/AAH) is controversial. Important long-term concerns
      include arch growth. We report our results obtained with a one-stage radical
      approach of coarctectomy and aortic arch advancement for NCoAo/AAH. METHODS: From
      June 1995 to December 2000, 65 newborns with NcoAo/AAH underwent coarctectomy and
      aortic arch advancement via a median sternotomy under deep hypothermic
      circulatory arrest. Patients were classified by diagnosis: group 1, isolated
      NCoAo/AAH (n = 13); group 2, NCoAo/AAH with ventricular septal defect (n = 20);
      and group 3, NCoAo/AAH with complex cardiac lesions (n = 32). RESULTS: The study
      population included 36 boys and 29 girls. Mean age was 13 +/- 1.7 days (range 1
      to 43 days). Mild to moderate left ventricular outflow tract obstruction was
      present in 15 patients. Mean body weight was 3.4 +/- 0.1 kg (range 1.6 to 5 kg).
      Eight babies were premature. The mean Z value for the aortic arch was -4 +/- 0.3
      (range -2 to -4.5) and for the isthmus -4.5 +/- 0.2 (range -3 to -7). Mean deep
      hypothermic circulatory arrest time was 28 +/- 2 minutes (range 14 to 60
      minutes). Mean intensive care unit stay was 6 +/- 1 days (range 2 to 30 days).
      There were three early deaths (all in groups 2 and 3) and two late deaths (in
      group 3) (5-year actuarial survival, 91% +/- 7.9%). There was one recurrence (5
      year actuarial freedom from recurrence, 98% +/- 4%). Peak Doppler velocity across
      the arch in the remaining patients was 1 +/- 0.1 m/s (range 0 to 2.2 m/s).
      CONCLUSIONS: Coarctectomy and aortic arch advancement is the optimal surgical
      method for management of NCoAo/AAH. It has low operative morbidity and mortality
      and a very low incidence of recoarctation or arch obstruction.

PMID- 11998818
TI  - Symptomatic Bochdalek hernia in an octogenarian.
AB  - We present a case of an 88-year-old man who presented with chest pain and
      shortness of breath. Chest radiography suggested the presence of a ruptured
      diaphragm, and on exploration a left Bochdalek defect with herniation of stomach
      and small bowel into the left pleural cavity was found. This was repaired and the
      patient eventually was discharged to a nursing facility. We believe this
      represents the oldest patient presentation of a symptomatic Bochdalek hernia.

PMID- 11998819
TI  - Precise quantification of pulsatile flow.

PMID- 11998820
TI  - Medial dorsal thalamic lesions impair blocking and latent inhibition of the
      conditioned eyeblink response in rats.
AB  - The effects of lesions of the medial dorsal thalamic nucleus (MD) on blocking and
      latent inhibition (LI) of the rat eyeblink response were examined in the present
      study. Previous work has demonstrated that the cingulate cortex and related
      thalamic areas are involved in processing conditioning stimuli throughout
      training. The experiments in the present study tested the hypothesis that
      disruption of cingulothalamic stimulus processing produced by lesions of the MD
      would impair 2 types of associative learning that involve decremental changes in
      attention. In Experiment 1, MD lesions severely impaired blocking. In Experiment
      2, MD lesions severely impaired LI. The results indicate that lesions of the MD
      impair incremental, decremental, or both types of changes in stimulus processing
      during learning.

PMID- 11998821
TI  - ACFAS universal foot and ankle scoring system: forefoot (module 2). American
      College of Foot and Ankle Surgeons.
AB  - The American College of Foot and Ankle Surgeons developed the Universal
      Evaluation Scoring System to evaluate parameters related to foot and ankle
      surgery. The project was developed in four sections or modules. The second of
      these modules, Forefoot, is presented here.

PMID- 11998823
TI  - Characterisation of novel modified active carbons and marine algal biomass for
      the selective adsorption of lead.
AB  - This paper discusses the sorption performance of novel materials for the removal
      of lead(II) and copper(II) from near-neutral aqueous solutions. Active carbons
      with surface heteroatoms of oxygen and phosphorus have been prepared. The surface
      functional groups display weakly acidic ion exchange characteristics. The optimum
      solution pH for maximum metal sorption is related to the pK values of the surface
      functional groups. In oxygenated active carbons, pK values are not distinct but
      can be obtained by describing proton binding to the heterogeneous adsorbent
      surface as a continuous proton affinity distribution. Information derived from
      zeta-potential measurements combined with knowledge of the pK distribution
      function and concentration of surface functional groups has been used to explain
      the selectivity of oxidised active carbons towards lead(lI) in the presence of
      copper(II) from multi-metal bearing solutions. Marine algal-based biosorbents
      have been challenged with lead(II) and copper(II)-bearing wastewater. The weakly
      acidic carboxyl groups of structural polysaccharides present within the algal
      matrix display high sorption capacity for both metals. The negative surface
      charge of algal particles results in electrostatic interactions as well as
      coordination between metal species and the adsorbent surface. Proton affinity for
      the algal surface lowers the negative surface potential at pH values around 2.
      The surface functional groups in algae unlike those in oxidised active carbons
      may be represented by discrete acid-dissociation constant values. The influence
      of conformational differences in uronic-acid segments upon metal ion selectivity
      is discussed.

PMID- 11998822
TI  - Optimization of biofiltration for odor control: model calibration, validation,
      and applications.
AB  - A dynamic model that describes the biofiltration process for hydrogen sulfide
      removal from wastewater treatment plant air emissions was calibrated and
      validated using pilot- and full-scale biofilter data obtained from the Cedar
      Rapids (Iowa) Water Pollution Control Facilities. After calibration, the model
      was found to predict the dynamic effluent concentrations of the pilot- and full
      scale biofilters well, with the measured data falling within 58 to 80% of the
      model output values. In addition, the model predicted the trend of the field
      data, even under field conditions of changing input concentration and at effluent
      concentrations below 1 ppm by volume. The model demonstrated that increasing gas
      residence time and temperature and decreasing influent concentration decreases
      effluent concentration. In addition, model simulations showed that a longer
      residence time is required to treat dynamic loading increases, indicating that
      biofilter design should account for the maximum influent concentration. These
      results can be used to help design and operate biofilters for controlling odorous
      and hazardous air emissions.

PMID- 11998824
TI  - Soil microbial population dynamics following bioaugmentation with a 3
      chlorobenzoate-degrading bacterial culture. Bioaugmentation effects on soil
      microorganisms.
AB  - Changes in microbial populations were evaluated following inoculation of
      contaminated soil with a 3-chlorobenzoate degrader. Madera sandy loam was amended
      with 0, 500, or 1,000 microg 3-chlorobenzoate g(-1) dry soil. Selected microcosms
      were inoculated with the degrader Comamonas testosteroni BR60. Culturable
      bacterial degraders were enumerated on minimal salts media containing 3
      chlorobenzoate. Culturable heterotrophic bacteria were enumerated on R2A.
      Isolated degraders were grouped by enterobacterial repetitive intergenic
      consensus sequence-polymerase chain reaction fingerprints and identified based on
      16S ribosomal-DNA sequences. Bioaugmentation increased the rate of degradation at
      both levels of 3-chlorobenzoate. In both the 500 and 1,000 microg 3
      chlorobenzoate g(-1) dry soil inoculated microcosms, degraders increased from the
      initial inoculum and decreased following degradation of 3-CB. Inoculation delayed
      the development of indigenous 3-chlorobenzoate degrading populations. It is
      unclear if inoculation altered the composition of indigenous degrader
      populations. In the uninoculated soil, degraders increased from undetectable
      levels to 6.6 x 10(7) colony-forming-units g(-1) dry soil in the 500 microg 3
      chlorobenzoate g(-1) dry soil microcosms, but none were detected in the 1,000
      microg 3-chlorobenzoate g(-1) dry soil microcosms. Degraders isolated from
      uninoculated soil were identified as one of two distinct Burkholderia species. In
      the uninoculated soil, numbers of culturable heterotrophic bacteria initially
      decreased following addition of 1,000 microg 3-chlorobenzoate g(-1) dry soil.
      Inoculation with C. testosteroni reduced this negative impact on culturable
      bacterial numbers. The results indicate that bioaugmentation may not only
      increase the rate of 3-chlorobenzoate degradation but also reduce the deleterious
      effects of 3-chlorbenzoate on indigenous soil microbial populations.

PMID- 11998825
TI  - [Clinic-radiographic correlation. Case 3/2002 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 11998826
TI  - Genetic bases of hypertrophic cardiomyopathy.

PMID- 11998827
TI  - Prevention of Escherichia coli respiratory infection in broiler chickens with
      bacteriophage (SPR02).
AB  - Bacteriophages are viruses that can infect and kill bacteria. Three studies were
      conducted to determine the efficacy of bacteriophage to prevent an Escherichia
      coli respiratory infection in broiler chickens. In the first study 3-d-old-birds
      were challenged with an air sac inoculation of 10(3) cfu of E. coli per mL mixed
      with either 10(3) or 10(6) pfu of bacteriophage, or 10(4) cfu E. coli mixed with
      10(4) or 10(8) pfu of bacteriophage. In the second study, drinking water of birds
      to 1 wk of age was treated with 10(3) or 10(4) pfu of bacteriophage per mL and
      birds were air sac challenged with 10(3) cfu of E. coli, or water was treated
      with 10(4) or 10(6) pfu of bacteriophage per milliliter and birds were challenged
      with 10(4) cfu of E. coli. In the third study, birds were air sac challenged at 1
      wk of age with 10(4) cfu of E. coli and given 10(5) or 10(6) pfu of bacteriophage
      per mL of water from 1 d of age to 2 wk of age. In Studies 1 and 2, there were
      two replicate pens per treatment with 10 birds per pen, and in Study 3, there
      were four replicate pens per treatment with 10 birds per pen. The studies were
      all concluded when the birds were 3 wk of age. In Study 1, BW was decreased at 1
      and 2 wk of age in the birds that were challenged with 10(3) or 10(4) cfu of E.
      coli and was decreased at 2 wk of age in the birds challenged with 10(4) cfu of
      E. coli mixed with 10(4) pfu of the bacteriophage. Mortality was decreased from
      80% in the birds challenged with 10(3) cfu of E. coli to 25 and 5% when mixed
      with 10(3) or 10(6) pfu of the bacteriophage, respectively. Mortality was
      decreased from 85% in birds challenged with 10(4) cfu of E. coli to 35% when
      mixed with 10(4) pfu of the bacteriophage, and no mortality occurred when mixed
      with 10(8) pfu of bacteriophage. There was essentially no protection observed in
      Studies 2 and 3 when the birds were challenged with 10(3) or 10(4) cfu of E. coli
      with bacteriophage present in their drinking water at any level. These data
      suggest that bacteriophage can protect birds from a respiratory challenge with E.
      coli, but that adding the bacteriophage to the drinking water offered no
      protection to the birds. The complete protection of the birds observed in Study 1
      suggests that bacteriophage may possibly be developed as an alternative to
      antibiotic use in poultry.

PMID- 11998828
TI  - Parameter optimization of a computer-aided diagnosis scheme for the segmentation
      of microcalcification clusters in mammograms.
AB  - Our purpose in this study is to develop a parameter optimization technique for
      the segmentation of suspicious microcalcification clusters in digitized
      mammograms. In previous work, a computer-aided diagnosis (CAD) scheme was
      developed that used local histogram analysis of overlapping subimages and a fuzzy
      rule-based classifier to segment individual microcalcifications, and clustering
      analysis for reducing the number of false positive clusters. The performance of
      this previous CAD scheme depended on a large number of parameters such as the
      intervals used to calculate fuzzy membership values and on the combination of
      membership values used by each decision rule. These parameters were optimized
      empirically based on the performance of the algorithm on the training set. In
      order to overcome the limitations of manual training and rule generation, the
      segmentation algorithm was modified in order to incorporate automatic parameter
      optimization. For the segmentation of individual microcalcifications, the new
      algorithm used a neural network with fuzzy-scaled inputs. The fuzzy-scaled inputs
      were created by processing the histogram features with a family of membership
      functions, the parameters of which were automatically extracted from the
      distribution of the feature values. The neural network was trained to classify
      feature vectors as either positive or negative. Individual microcalcifications
      were segmented from positive subimages. After clustering, another neural network
      was trained to eliminate false positive clusters. A database of 98 images
      provided training and testing sets to optimize the parameters and evaluate the
      CAD scheme, respectively. The performance of the algorithm was evaluated with a
      FROC analysis. At a sensitivity rate of 93.2%, there was an average of 0.8 false
      positive clusters per image. The results are very comparable with those taken
      using our previously published rule-based method. However, the new algorithm is
      more suited to generalize its performance on a larger population, depends on two
      monotonic outputs making its evaluation much easier and can be trained in an
      automatic way making practical its application on a large database.

PMID- 11998829
TI  - Gonadal sperm reserve in purebred Landrace and Large White boars of high average
      daily gain.
AB  - The present study investigated the effects of average growth rate (AGR) levels
      and age on the number of sperm cells per gram of testis parenchyma and on the
      gonadal reserve in Landrace (LD) and Large White (LW) boars. In Experiment 1, the
      effects of breed (LD, LW), level of AGR from birth up to 90 days of age (Level 1:
      384 +/- 32 g/day; Level 2: 512 +/- 22 g/day; Level 3: 624 +/- 41 g/day), and age
      (13, 15, 17, 19 and 21 weeks) on testicular cell concentration were evaluated.
      Data were analyzed under a 2 x 3 x 4 factorial design. There were significant
      effects associated with breed (P < 0.001) and age (P < 0.001) but not with AGR (P
      > 0.05) on sperm cell number per gram of testicular parenchyma. The number of
      cells increased with age and was greater in LW than in LD young boars, mainly
      those up to 19 weeks of age. In Experiment 2, the effect of two AGR levels (Level
      1: 649-694 g/day; Level 2: 813-885 g/day) from birth up to 100 kg body weight on
      the number of sperm cells per gram of testis parenchyma and on the gonadal
      reserve was investigated using 59 purebred LD and LW boars. The boars were
      castrated at 23, 25, 29 and 33 weeks of age. Age of boars significantly affected
      gonadal sperm reserve and the number of sperm cells per gram of testicular tissue
      (P < 0.001). Breed of boars and AGR Levels did not significantly affect number of
      sperm cells and gonadal sperm reserve (P > 0.05). It was concluded that the
      number of sperm cells in the testicular tissue of young boars is influenced by
      their breed and age, but not by the level of their AGR.

PMID- 11998830
TI  - Administration of sulpiride to anovulatory mares in winter: effects on prolactin
      and gonadotropin concentrations, ovarian activity, ovulation and hair shedding.
AB  - Sixteen seasonally anovulatory mares were randomly allotted to two groups and
      injected daily with either sulpiride (1 mg/kg body weight) or vehicle from 14
      January to 14 February. Sulpiride administration increased daily plasma prolactin
      concentrations (P < 0.05), although the prolactin response during the 6 h
      following sulpiride injections decreased markedly from the 1st to the 6th day of
      treatment (treatment by day, P < 0.0001). Plasma concentrations of LH and FSH
      were not affected by treatment (P > 0.1). Injection of GnRH and TRH on 15
      February showed that the response of plasma prolactin to secretagogue was
      increased in sulpiride-treated mares (P < 0.005), while there was no effect (P >
      0.1) of sulpiride treatment on the response of LH or FSH. Both treatment groups
      had similar changes in numbers of follicles 10-19 and > or = 20 mm during the
      experiment (P > 0.1). Similarly, the mean change in maximal follicular size was
      not affected by treatment (P > 0.9). No mare ovulated during the study, and
      plasma progesterone concentrations were similar in both groups (P > 0.1), always
      at levels < 1 ng/ml. Hairshedding increased with time in all mares (P < 0.001)
      and was increased by sulpiride injections (P = 0.09). It was concluded that
      sulpiride administration to seasonally anovulatory mares under the conditions of
      our experiment increased daily plasma prolactin levels but did not stimulate
      gonadotropin secretion or ovarian activity.

PMID- 11998832
TI  - Early versus late surgery for intractable seizures.
AB  - Certain drug-resistant epilepsies are highly responsive to surgery. Dr. Engel
      argues that there is no need to pursue exhaustive drug trials with these
      patients. If the first-line anticonvulsants fail, they should be referred
      directly to an epilepsy center and considered for surgical treatment.

PMID- 11998831
TI  - Comparative effects of water immersion pretreatment on three different acute
      pancreatitis models in rats.
AB  - Cells respond to stress by upregulating the synthesis of cytoprotective heat
      shock proteins (HSPs) and antioxidant enzymes. The aim of this study was to
      compare the effects of cold (CWI) or hot water immersion (HWI) stress on three
      different acute pancreatitis models (cholecystokinin octapeptide (CCK), sodium
      taurocholate (TC), and L-arginine (Arg)). We examined the levels of pancreatic
      HSP60, HSP72, and antioxidants after the water immersion stress. Male Wistar rats
      were injected with CCK, TC, or Arg at the peak level of pancreatic HSP synthesis,
      as determined by Western blot analysis. HWI significantly elevated HSP72
      expression and CWI significantly increased HSP60 expression in the pancreas.
      Water immersion stress decreased the levels of pancreatic antioxidants. CWI and
      HWI pretreatment ameliorated most of the examined laboratory and morphological
      parameters of CCK-induced pancreatitis. CWI pretreatment decreased pancreatic
      edema and the serum amylase level; however, the morphological damage was more
      severe in TC-induced acute pancreatitis. Overall, CWI and HWI pretreatment only
      decreased the serum cytokine concentrations in Arg-induced pancreatitis. CWI and
      HWI resulted in differential induction of pancreatic HSP60 and HSP72 and the
      depletion of antioxidants. The findings suggest the possible roles of HSP60 and
      (or) HSP72 (but not that of the antioxidant enzymes) in the protection against
      CCK- and TC-induced acute pancreatitis. Unexpectedly, CWI pretreatment was
      detrimental to the morphological parameters of TC-induced pancreatitis. It was
      demonstrated that CWI and HWI pretreatment only influenced cytokine synthesis in
      Arg-induced pancreatitis.

PMID- 11998833
TI  - [Experiencing the educational process in nursing with high risk pregnant women
      and their companions].
AB  - The present study is a picture of the educational process lived by hospitalized
      high-risk pregnant women and also by their companions, conducted at the
      University Hospital of the Federal University of Santa Catarina. It has been
      developed as a joint process with the clients, through dynamic interaction, as a
      set of actions in an effort to socialize knowledge and experiences. The goal is
      to offer greater autonomy to the clients, allowing the high risk pregnancy to be
      a peaceful, safe and joyful experience, beyond the fact of contributing with the
      construction of new knowledge about the being-and-living process of these women.

PMID- 11998834
TI  - Radiocarbon as a tool to apportion the sources of polycyclic aromatic
      hydrocarbons and black carbon in environmental samples.
AB  - To determine the relative inputs of polycyclic aromatic hydrocarbons (PAHs) and
      black carbon (BC) in environmental samples from the combustion of fossil fuels
      and biomass, we have developed two independent analytical methods for determining
      the 14C abundance of PAHs and BC. The 5730 yr half-life of 14C makes it an ideal
      tracer for identifying combustion products derived from fossil fuels (14C-free)
      versus those stemming from modern biomass (contemporary 14C). The 14C abundance
      of PAHs in several environmental Standard Reference Materials was measured by
      accelerator mass spectrometry after extraction and then purification by high
      performance liquid chromatography and preparative capillary gas chromatography.
      This method yields pure compounds that allow for a high degree of confidence in
      the 14C results. The PAHs data were then used to compare and evaluate results
      from an operationally defined thermal oxidation method used to isolate a BC
      fraction. The 14C compositions of PAHs and BC were very similar and suggest that
      the thermal oxidation method employed for isolating BC is robust and free from
      interferences by non-BC components. In addition, these data indicate that both
      the PAHs and the BC species derive mostly from fossil fuels and/or their
      combustion products.

PMID- 11998835
TI  - Recognition and management of acute pesticide poisoning.
AB  - Most poisonings from pesticides do not have a specific antidote, making
      decontamination the most important intervention. For maximal benefit to the
      patient, skin, eye, and gastric decontamination should be undertaken while
      specifics of the poisoning are being determined. As in most illnesses and
      injuries, the history of the poisoning is of great importance and will determine
      specific needs for decontamination and therapy, if any exist. Protection of
      health care workers during the decontamination process is important and
      frequently overlooked. Skin decontamination is primarily accomplished with large
      volumes of water, soap, and shampoo. Gastric decontamination by lavage is
      indicated if ingestion of the poisoning has occurred within 60 minutes of patient
      presentation. Activated charcoal, combined with a cathartic, is also indicated in
      most poisonings presenting within 60 minutes of ingestion. With large volume
      ingestion poisonings, activated charcoal may be used after 60 minutes, but little
      data exist to support this practice. Syrup of ipecac is no longer recommended for
      routine use. The cholinergic syndrome "all faucets on" characterizes poisoning by
      organophosphates and carbamates. Organochlorine insecticides (lindane and other
      treatments for scabies and lice) can produce seizures with excessive use or use
      on large areas of nonintact skin. Non-dipyridyl herbicides, biocides (including
      pyrethrins, pyrethroids, and Bacillus thuringiensis) rarely produce anything
      other than mild skin, eye, and/or gastrointestinal irritation on topical exposure
      or ingestion.

PMID- 11998837
TI  - Bibliography. Current world literature. Renal immunology and pathology.

PMID- 11998836
TI  - Thermodynamic parameters for the binding of polycarboxylic anions by fully methyl
      substituted linear polyammonium cations.
AB  - Enthalpy changes for the binding of malonate, citrate, 1,2,3
      propanetricarboxylate and 1,2,3,4-butanetetracarboxylate by fully methyl
      substituted linear polyammonium cations (with the general formula C3nNnH(8n +
      2)n+, with n = 1,2,3) were determined calorimetrically. Enthalpy changes were
      also determined for the binding of malonate by unsubstituted polyammonium cations
      (with the general formula C2(n - 1)NnH(6n - 2)n+, n = 1...6). delta H0/kJ mol-1
      values are always positive and strongly dependent on the charges involved in the
      formation reaction. Mean values for delta G0 and T delta S0 were obtained as a
      function of the charge product zeta = Zanion/ Zcation: -delta G0/kJmol-1 = (4.0
      +/- 0.4) zeta, T delta S0/kJmol-1 = (5.9 +/- 0.1) zeta (substituted polyamines),
      and -delta G0/kJmol-1 = (3.5 +/- 0.2) zeta, T delta S0/kJmol-1 = (5.0 +/- 0.4)
      zeta (unsubstituted polyamines). For both classes of amines it was found that T
      delta S0 vs. delta G0 is linear with a correlation coefficient of r = 0.9618.
      Crude approximation gives -delta G0/kJmol-1 = (7.0 +/- 0.4) n-1, T delta S0/kJmol
      1 = (10.0 +/- 0.8) n-1 for unsubstituted amines and -delta G0/kJmol-1 = (8.0 +/-
      0.8) n-1, T delta S0/kJmol-1 = (11.8 +/- 2.0) n-1 (n = number of possible salt
      bridges, or single interactions) for substituted amines.

PMID- 11998838
TI  - Bibliography. Current world literature. Epidemiology and prevention.

PMID- 11998839
TI  - JAMA patient page. Altitude sickness.

PMID- 11998840
TI  - Anaerobic reduction of a sulfonated azo dye, Congo Red, by sulfate-reducing
      bacteria.
AB  - The capacity for anaerobic decolorization of a sulfonated azo dye, Congo Red, by
      a strain of a sulfate-reducing bacterium was evaluated. After optimizing the
      growth rate of the bacteria on a simple carbon source and terminal electron
      acceptor pair, lactate and sulfate, respectively, the effect of the dye
      concentration on their growth rate was analyzed. The decolorization rate was
      affected by the dye concentration in the growth medium. The azo-bond cleavage
      mechanism of reductive decolorization with the formation of benzidine was
      consistent with the results, as this metabolite was identified by high
      performance liquid chromatography. Several fractions of the culture medium,
      including lysed cell extracts, were examined for the capacity to reduce the azo
      dye. This reduction capacity was found in the culture medium in which the cells
      had previously grown. The results showed that the mechanism of reductive
      decolorization of this sulfonated azo dye was extracellular and nonenzymatic,
      consistent with the production of sulfide anion by the microorganisms while
      growing on lactate and sulfate. The sulfide anions were the cause of the
      reduction leading to the disappearance of color in the medium. To increase the
      rate of decolorization, the presence of ferrous ion was also necessary together
      with the lactate and sulfate substrates.

PMID- 11998841
TI  - Optimization of yield in kinetically controlled synthesis of ampicillin with
      immobilized penicillin acylase in organic media.
AB  - Immobilized penicillin acylase is a moderately priced versatile enzyme, that is
      able to catalyze the synthesis of derived penicillins and cephalosporins from the
      corresponding beta-lactam nuclei and proper side-chain precursors. Kinetically
      controlled synthesis is a better strategy when product yield is a key issue.
      Yield should increase at reduced water activity by depressing the competing
      hydrolytic reactions in favor of synthesis; therefore, organic cosolvents can be
      a suitable reaction media for synthesis. Using response surface methodology and
      product yield as objective function, temperature and pH were optimized in the
      kinetically controlled synthesis of ampicillin using previously screened
      cosolvents and reaction conditions. Optimum pH was 6.0 for ethylene glycol (EG)
      and glycerol (GL) and 6.6 for 1-2 propanediol (PD); optimum temperature was 30
      degrees C for GL and for EG and PD was in the lower extreme of the range studied,
      optimum lying below 26 degrees C. Maximum molar yields predicted by the model
      were 58,51, and 46% for EG, GL, and PD, respectively, which were experimentally
      validated. Highest yield in aqueous buffer was always <40%. Molar yields about
      60% compare favorably with values reported for the kinetically and
      thermodynamically controlled synthesis of ampicillin and other derived
      penicillins.

PMID- 11998842
TI  - Application of spontaneous suction phase-dispersing (SSPD) extractors in the
      extraction of penicillin G.
AB  - The extraction of penicillin G from an aqueous solution with butyl acetate (BA)
      and tributyl phosphate (TBP) as extractants was carried out at pH 4 with
      spontaneous suction phase-dispersing (SSPD) extractors under various operating
      conditions. Four kinds of SSPD extractors were tested with results compared to
      those obtained by using an extractor with mechanical stirrers. Rotation speed and
      different extraction systems were found to influence the penicillin recovery and
      the stability of emulsion formed during extraction. The percentage of extraction
      under optimum conditions was 91% without formation of emulsion. The laser
      particle size measurement instrument combined with SSPD can be used to measure
      the emulsion droplet size in situ.

PMID- 11998843
TI  - Production, purification, and characterization of a polygalacturonase from a new
      strain of Kluyveromyces marxianus isolated from coffee wet-processing wastewater.
AB  - A new high polygalacturonase (PG)-producing Kluyveromyces marxianus strain was
      isolated from coffee wet-processing wastewater. PG production in this strain is
      not repressed in the presence of 100 g/L of glucose and, being growth-associated,
      reached its maximum accumulation in the culture medium at the beginning of the
      stationary phase. Oxygen and galacturonic acid negatively regulated enzyme
      synthesis, and glucose as the carbon source afforded better enzyme yields than
      lactose. The data reported here show that this strain exhibits the highest index
      of PG production among the wild-type strains reported so far (18.8 U/mL). PG was
      readily purified by ion-exchange chromatography on SP-Sepharose FF. The activity
      corresponded to a single protein with an M(r) of 41.7kDa according to sodium
      dodecyl sulfatepolyacrylamide gel electrophoresis. The enzyme was stable in the
      pH range of 3.0-5.0 and displayed an optimal temperature of 55 degrees C; it
      showed a typical endosplitting way of substrate hydrolysis and exhibited a fair
      degree of activity on pectin with a high degree of esterification.

PMID- 11998844
TI  - Nutritional profile of food yeast Kluyveromyces fragilis biomass grown on whey.
AB  - Biomass of food yeast Kluyveromyces fragilis (MTCC 188) grown on deproteinized
      whey supplemented with 0.8% diammonium hydrogen phosphate and 10 ppm indole-3
      acetic acid, had a crude protein content of 37%. The true protein content based
      on nitrogen fractionation procedure was 28.1%. Total nucleic acid content was
      4.82%. This amount does not appear to be toxicologically offensive. Crude fiber,
      ash, and lipid content of K.fragilis dry cells were found to be 4.9%, 16%, and
      7.8%, respectively. Essential fatty acids of both omega-3 and omega-6 series were
      found present in the fat of the yeast and represented 21.5% of the total fatty
      acids. All the essential amino acids were present in the proteins of K. fragilis;
      however, sulfur containing amino acids were found in lower amounts. Calculated
      protein scores indicate moderate biological value. B vitamins in the biomass were
      present as expected, but folic acid and pyridoxine were present in high
      concentration.

PMID- 11998845
TI  - Cellular, pharmacokinetic, and pharmacodynamic aspects of response to
      camptothecins: can we improve it?
AB  - The camptothecins provide a novel class of effective anticancer agents that exert
      their action against DNA topoisomerase I. Members of the camptothecins include
      topotecan, irinotecan, 9-aminocamptothecin, and 9-nitrocamptothecin, which are
      analogs of the plant alkaloid 20(S)-camptothecin. These agents vary in their
      antitumor efficacy and toxicity. Several pharmacokinetic and pharmacodynamic
      factors including cellular efflux, modulation of topoisomerases I and II, lactone
      stability, alterations in metabolism, and drug-drug interactions, influence the
      antitumor response and toxicity of these agents. Preclinical studies suggest that
      protracted schedules of administration produce greater antitumor effect than
      bolus administration. However, the optimal treatment regimens and administration
      schedules of these agents have yet to be established in clinical studies.

PMID- 11998846
TI  - Stem cells from a biological perspective: what they are, where they are found,
      and what can be done with them.

PMID- 11998847
TI  - Embryonic stem cell research and respect for human life: philosophical and legal
      reflections.

PMID- 11998848
TI  - Human cloning and the right to reproduce.

PMID- 11998849
TI  - Human cloning and genetic engineering: the case for proceeding cautiously.

PMID- 11998850
TI  - Biotech and theodicy: what can and what ought we to do in procreative technology?

PMID- 11998851
TI  - The ethics weave in human genomics, embryonic stem cell research, and therapeutic
      cloning: promoting and protecting society's interests.

PMID- 11998852
TI  - Ethical issues in stem cell research.

PMID- 11998853
TI  - "The American Breed": Nazi eugenics and the origins of the Pioneer Fund.

PMID- 11998854
TI  - A comparative look at the U.S. and British approaches to stem cell research.

PMID- 11998855
TI  - Effects of space flight factors on the heredity of higher and lower plants.
AB  - The effects were studied of a long-term space exposure (72 days) aboard the
      Salyut orbital station on the following: dry seeds of Crepis capillaris (L.)
      Wallr. and Arabidopsis thaliana (L.) Heynh, haploid and diploid strains of
      Saccharomyces cerevisiae mutant for adenine locus (ad) and strain LARG-I of
      Chlorella vulgaris Beijer. A modifying effect of space factors on radiobiological
      action of gamma-irradiation from 137Cs was determined with the higher plant seeds
      and Chlorella culture. For this, the material was partly irradiated prior to, and
      partly after the flight at doses of 3, 30 and 10 kr for C. capillaris, A.
      thaliana and Chl. vulgaris, respectively. It was shown that: (1) Space factors
      caused reduced survival of Arabidopsis seedlings and Chlorella and yeast
      cultures, reduced productivity of Chlorella cells, increased mutability of
      Chlorella and yeast cells and increased frequency of chromosome aberrations in
      cells of Crepis root meristem. There are, however, a few exceptions: cell
      germination of C. capillaris was enhanced while mutability of A. thaliana seeds
      declined. (2) Space factors increased the adverse effects of the pre-flight
      irradiation on all the parameters of the cultures tested. (3) Space factors had
      no genetic effect on the objects tested. They have, however, caused a stronger
      inhibition of seed germination and augmenting survival of A. thaliana seedlings
      and Chlorella cells.

PMID- 11998856
TI  - Results of cytogenetic studies of seeds after their extended orbital flight
      aboard the Salyut orbital scientific station.
AB  - Air-dry seeds of Lactuca sativa (lettuce) with a different level of spontaneous
      mitagenesis were used in these experiments. A part of the seeds was given pre
      flight gamma radiation in doses of 1 and 10 krads. Comparison of the results for
      the in-flight experiments, laboratory and "transport" control showed an increase
      of cells with chromosome aberrations and an increase of radiobiological effect in
      irradiated seeds flown aboard the Salyut scientific station. A comparative
      analysis was made of the cytogenetic changes in seeds after their exposure to
      different periods of weightlessness during the Cosmos 368, Zond 8 and Salyut
      missions. The effect of weightlessness of different duration on the development
      of cytogenetic changes in irradiated and unirradiated seeds is discussed.

PMID- 11998857
TI  - Human sensorimotor coordination following space flights.
AB  - Studies have been carried out 18-30 days before the flight and on the second day
      after landing. The recovery kinetics of cosmonauts who completed the 18-day space
      flight was followed for 30 days after their return. Muscle tone, indices of
      muscle strength and parameters of the functions of the extremities were examined,
      and the ability to maintain vertical posture was studied (stabilography). Flights
      of short duration did not cause any serious disturbances in the neuromuscular
      system. Together with this fact, the analysis of the results revealed a certain
      regularity in the physiological effects as reflected by a decrease in the
      strength of the torso extensors and the muscle tone of the lower extremities, The
      tone and strength of the arms altered insignificantly, and the alterations were
      not an indication of muscular atrophy. Stabilographic studies showed a decrement
      in the stability of the vertical posture of the cosmonauts. The above alterations
      were particularly pronounced in the crew members of Soyuz 9. As distinct from the
      previous flights of the Soyuz spaceships the crew members of Soyuz 9 showed
      normality in the regulation of vertical posture only on the tenth day after the
      flight. One of the reasons for the above alterations in postural regulation may
      be the decrease in muscle tone noted repeatedly after both of the previous space
      flights and in experiments with simulation of separate effects of weightlessness.
      Another reason for the deterioration in postural regulation is probably the
      changes in interaction between the neutral analysers. A possible reason for the
      apparent defects in stability may be the disturbance of the interaction between
      various muscle groups, i.e. the disturbance in synergism which is required for
      the maintenance of vertical posture. Similar alterations were observed in people
      who had been subjected to bed rest for a long time. Readaptation to the ground
      environment appeared to proceed in stages. The comparative evaluation of post
      flight findings showed that prolonged periods of flights up to 18 days resulted
      in more pronounced alterations in human sensomotor coordination.

PMID- 11998858
TI  - Antarctica as a Martian model.
AB  - Previous investigators have reported that the microbiological population of the
      glacier free valleys of southern Victorialand, Antarctica, is sparse, and that
      from about 10% of the soil samples examined no micro-organisms could be
      cultivated. Since these areas are assumed to be more favorable to the growth of
      terrestrial organisms than any Martian environment, the previous authors
      concluded that the probability of terrestrial organisms growing on Mars would
      therefore be so small that sterilization standards could be relaxed by many
      orders of magnitude. The unsuitability of the Antarctic environment to the
      multiplication of terrestrial micro-organisms was ascribed by them to limiting
      amounts of water. We have carried out a survey of a variety of environments in
      the dry valleys, ranging from mountain crests to valley floors. The main purpose
      of our investigation was the determination of active microbial multiplication in
      the soil. A series of techniques was employed which permitted the detection of
      bacterial growth in situ. All evidence points to an active growth of micro
      organisms in the Antarctic soil in all locations which we examined. The
      measurements were supported by electron micrographs of soil films which showed
      colonial growth covering soil particles. These findings suggest that Antarctica
      does not serve as a useful model for the Martian environment in evaluating
      quarantine standards.

PMID- 11998859
TI  - Life sciences and space research XI. Proceedings of the Open Meeting of the
      Working Group on Space Biology of the Fifteenth Plenary Meeting of COSPAR,
      Madrid, Spain, 10-24 May 1972.

PMID- 11998860
TI  - Organic analysis of lunar samples and the Martian surface.
AB  - In addition to the organogenic elements (H, C, N, O, S, P) which are necessary
      for the synthesis of organic molecules, the lunar samples from Apollo 11, 12, 14
      and 15 contain substantial amounts (approximately equal to 10 to 100 microgram/g)
      of CO, N2 and CO2, which are released at relatively high temperatures and smaller
      amounts (approximately equal to 0.1 to 10 microgram/g) of more complex organic
      compounds (e.g. benzene). Most of these analyses have been performed by mass
      spectrometry or by combined gas chromatography-mass spectrometry after
      appropriate volatilization. The release of very small amounts of water has also
      been observed and is consistent with the findings of goethite (FeO.OH) and with
      measurements by the suprathermal ion detector. The lunar surface provides one of
      the less favorable solar system models for the synthesis of organic compounds yet
      small amounts of these compounds have been detected in the returned samples. It
      is reasonable to assume that the different physical and developmental features of
      the planet Mars (increased gravitational field, presence of an atmosphere with
      CO2, CO and H2O, recent volcanic and tectonic activity, etc.) would favor an
      increased organic content of the surface of this planet relative to the moon.
      Therefore the organic molecules present in the Martian soil should be measurable
      by miniaturized mass spectrometers after fractional distillation or gas
      chromatographic separation of the volatiles released by moderate heating.

PMID- 11998861
TI  - Some results of medical investigations performed during the flight of the
      research orbital station Salyut.
AB  - The paper presents the main results of physiological studies carried out during
      the flight of the Salyut station. Details of atmospheric composition, diet,
      provisions for personal hygiene, the on-board medical kit, prophylactic measures,
      work and rest schedule are given. Methods of investigation, particularly for
      studying the cardiovascular response, are described, including tests using the
      application of lower body negative pressure. The subjective and objective in
      flight condition of the cosmonauts is dealt with in detail. An evaluation of the
      cardiovascular response is made, as compared with previous flights, both at rest
      and during tests. Results of clinical and biochemical studies of the blood,
      certain indices of visual perception and microbiological investigations are
      described. It is concluded that the observed physiological changes are
      reversible.

PMID- 11998862
TI  - Some psychological and engineering aspects of the extravehicular activity of
      astronauts.
AB  - One of the main in-flight problems being fulfilled by astronauts is the
      preparation for and realization of egress into open space for the purpose of
      different kinds of extravehicular activity, such as, the performance of
      scientific experiments, repairing and dismantling operations etc. The astronaut's
      activity outside the space vehicle is the most difficult item of the space flight
      programme, which is complicated by a number of space factors affecting a man,
      viz. dynamic weightlessness, work in a space suit under conditions of excessive
      pressure, difficulties of space orientation etc. The peculiarities mentioned
      require special training of the cosmonaut. The physical training involves a
      series of exercises forming the body-control habits necessary for work in a state
      of weightlessness. In a new kind of training use is made of equipment simulating
      the state of weightlessness. From analysis of the available data and the results
      of my own investigations during ground training and the Soyuz 4 and 5 flights one
      can establish the following peculiarities of the astronaut's extravehicular
      activity: (1) Operator response lag in the planned algorithm; (ii) systematic
      appearance of some stereotype errors in the mounting and dismantling of the outer
      equipment and in scientific-technical experiments; (iii) a high degree of
      emotional strain and 30-35% decrease in in-flight working capacity of the
      astronaut compared with the ground training data; (iv) a positive influence of
      space adaptation on the cosmonaut and the efficiency of his work in open space;
      (v) the necessity for further engineering and psychological analysis of the
      astronaut's activity under conditions of the long space flight of the multi
      purpose orbital station. One of the main reasons for the above peculiarities is
      the violation of the control-coordination functions of the astronaut in the
      course of the dynamical operations. The paper analyses the extravehicular
      activity of the astronaut and presents some recommendations for its more
      efficient realization. Proposals are given concerning the complex engineering,
      psychological and technical investigations to be made during in-flight egress.

PMID- 11998863
TI  - Early endosomes, late endosomes, and lysosomes display distinct partitioning
      strategies of inheritance with similarities to Golgi-derived membranes.
AB  - The pattern of inheritance of compartments of the endocytic pathway has been
      rarely reported, and the precise mechanism(s) are yet to be elucidated. We used
      antibodies reactive to early endosomes (anti-EEA1), late endosomes (anti-LBPA and
      anti-LAMP-1), lysosomes (anti-LAMP-1) and trans-Golgi network (TGN) (anti-GOLGA4)
      to examine the inheritance of these compartments in fixed human HEp-2 cells.
      Prior to entering M phase, these compartments display a perinuclear bias in their
      cytoplasmic distribution with areas of local accumulation juxtaposed to the
      centrosome. The location of these compartments during mitosis was examined
      relative to each other, the chromosomes, centrosomes and the microtubule network.
      During M phase early endosomes and TGN-derived compartments share overlapping
      subcellular distributions. A portion of these compartments display discernible
      clustering around the separated and migrating centrosomes in prophase. At
      metaphase these compartments co-localise with the mitotic spindle, are absent at
      the metaphase plate and do not overlay the astral microtubules. At anaphase these
      compartments are concentrated between shortening kinetochore microtubules and
      centrosomes. In addition, they appear distributed over the elongating polar
      microtubules in the body of the cell. From telophase and into cytokinesis these
      compartments concentrate around the minus ends of the constricted remnants of
      polar spindle microtubules and re-establish a prominent presence juxtaposed to
      the centrosome. In contrast, there is little evidence of movement of late
      endosomes and lysosomes with migrating centrosomes in prophase, and these
      compartments are excluded from the mitotic spindle at metaphase. However, by the
      end of telophase, the subcellular distribution of a portion of late endosomes and
      lysosomes share overlapping distributions with that of early endosomes. We
      conclude a portion of endosomal compartments and Golgi-derived membranes undergo
      ordered partitioning based on the centrosome and mitotic spindle.

PMID- 11998864
TI  - A novel protein localized to the fibrillar compartment of the nucleolus and to
      the brush border of a secretory cell.
AB  - We report the identification and molecular characterization of a novel abundant
      nucleolar protein of the dipteran Chironomus tentans. As shown by Western blot
      analysis, this protein is present in nuclear extracts in a phosphorylated form
      with a mobility corresponding to 100 kDa. Therefore, the protein has been termed
      Chironomus tentans p100, or p100 for short. Analysis of the cDNA-derived primary
      structure of p100 indicates a protein that contains a combination of structural
      domains which could be involved in interactions with proteins and nucleic acids:
      twelve alternating acidic and basic repeats, a glycine-arginine-rich domain and a
      region with two zinc fingers of the C4-type. Acidic and basic repeats are typical
      for a group of nonribosomal nucleolar proteins. The best-studied representatives
      of this group are Nopp140 and nucleolin, proteins with structural and regulatory
      functions in rDNA transcription. Immunocytology and immunoelectron microscopy of
      Chironomus tentans salivary gland cells have shown that the p100 protein is
      located in the fibrillar compartment of the nucleolus, while it is almost absent
      from the granular compartment and from the nucleoplasm. The p100 protein remains
      in the nucleolus after removal of RNA and DNA by digestion with nucleases. This
      indicates that p100 might be a constituent of the nucleolar proteinaceous
      framework. Remarkably, p100 is also localized in the brush border in the apical
      part of the salivary gland cell. The presence of p100 both in the nucleolus and
      at the apical plasma membrane suggests that it could be involved in coordination
      of the level of protein production and export from the cell through regulation of
      the level of rRNA production in the nucleolus.

PMID- 11998865
TI  - Induction of a hypertrophic growth status of coronary smooth muscle cells is
      associated with an overexpression of TGF-beta.
AB  - Hypertrophy of vascular smooth muscle cells occurs during hypertension-induced
      remodelling of arteries and during development of arteriosclerosis and restenosis
      following angioplasty but the pathogenesis of the hypertrophic status is not yet
      fully understood. In a previous study we demonstrated that the synthetic non
      sulfated, non-toxic heparin-mimicking compound RG-13577 is capable of inducing a
      cell cycle-arrested hypertrophic phenotype of coronary smooth muscle cells. In
      this study we clarify the mode of action of RG-13577 and demonstrate that the RG
      13577-induced hypertrophy is associated with an increased expression of TGF-beta1
      as indicated by an increase in TGF-beta1-specific protein and mRNA level.
      Furthermore we show that RG-13577-treated hypertrophic smooth muscle cells
      maintain full metabolic activity as indicated by a continuous de novo synthesis
      of protein and proteoglycans and that the RG-13577-induced growth arrest is
      caused not only by a higher expression of TGF-beta, but also by a reduced
      response of RG-treated cells to the mitogenic activity of bFGF, PDGF and EGF. The
      growth inhibitory activity of RG-13577 is reduced in the presence of neutralizing
      antibodies against TGF-beta. TGF-beta itself has anti-proliferative activity in
      serum-depleted medium. The RG-13577 effect is reversible since incubation of
      hypertrophic cells in RG-13577-free medium restores cell volume and [3H]thymidine
      incorporation to the values of untreated control cells within 4 days. We
      conclude, that the active metabolic status of RG-13577-treated cells in
      association with the overexpression of TGF-beta could promote repair processes of
      injured arteries after angioplasty without stimulating cell proliferation.

PMID- 11998866
TI  - Newly developed rat brain pericyte cell line, TR-PCT1, responds to transforming
      growth factor-beta1 and beta-glycerophosphate.
AB  - Brain pericytes form an incomplete envelope around endothelial cells and within
      the microvascular basement membrane of capillaries and postcapillary venules.
      Recently, it has been reported that brain pericytes exhibit pluripotency,
      regulation of endothelial cell activity, and macrophage activity. However, many
      molecular and cellular aspects of brain pericytes remain unclear. In this study,
      we have tried to establish a conditionally immortalized brain pericyte cell line
      (TR-PCT) derived from the brain capillary of a transgenic rat harboring a
      temperature-sensitive simian virus 40 T antigen gene. One of the clones was named
      TR-PCT1, and we established 6 clones of pericyte-like cells from a 16 week-old
      tsA58 transgenic rat. For comparison, primary pericytes from a Wistar rat were
      also studied. The expression of platelet-derived growth factor receptor beta,
      angiopoietin-1, osteopontin, and intercellular adhesion molecule-1 in TR-PCT1 was
      determined by reverse transcription-polymerase chain reaction. Transforming
      growth factor-beta1 enhanced a-smooth muscle actin expression in TR-PCT1, but
      this expression was reduced by subsequent treatment with basic fibroblast growth
      factor. When TR-PCT1 was seeded on type I collagen plates and treated with beta
      glycerophosphate, nodules developed in the cells and these nodules reacted
      positively to von Kossa stain used as a marker of calcification. We believe that
      TR-PCT1 will help us gain a better understanding of the physiological and/or
      pathophysiological role of pericytes.

PMID- 11998867
TI  - Fibroblasts derived from chronic diabetic ulcers differ in their response to
      stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls.
AB  - Patients with diabetes mellitus experience impaired wound healing, often
      resulting in chronic foot ulcers. Healing can be accelerated by application of
      growth factors like platelet-derived growth factor (PDGF). We investigated the
      mitogenic responses, measured by 3[H]thymidine incorporation, of fibroblasts
      cultured from diabetic ulcers, non-diabetic ulcers, and non-lesional diabetic and
      age-matched controls, to recombinant human PDGF-AB, epidermal growth factor
      (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF
      I). We determined the optimal concentration of these factors and investigated
      which single factor, or combination of factors, added simultaneously or
      sequentially, induced the highest mitogenic response. For single growth factor
      additions, in all fibroblast populations significant differences in mitogenic
      response to different growth factors were observed, with PDGF-AB consistently
      inducing the highest response and IGF-I the lowest (p < 0.043). IGF-I produced
      only a 1.7-fold stimulation over control in diabetic ulcer fibroblasts, versus
      2.95-fold for chronic ulcer, 3.2-fold for non-lesional (p = 0.007) and 5-fold for
      age-matched fibroblasts (p = 0.007). The highest mitogenic response induced by
      EGF was significantly less for chronic ulcer fibroblasts compared with age
      matched and nonlesional controls (p < 0.03), chronic ulcer fibroblasts also
      needed significantly more EGF to reach this optimal stimulus (p < 0.02 versus age
      matched and non-lesional controls). The simultaneous addition of FGF-IGF-I, PDGF
      IGF-I and FGF-PDGF to diabetic ulcer fibroblasts always produced a higher
      stimulatory response than sequential additions (p < or = 0.05). Also the addition
      of bFGF, PDGF-AB and EGF prior to IGF-I induced a higher 3[H]thymidine uptake in
      all fibroblasts compared to the combination of each in reverse order. Significant
      differences were observed when comparing the combinations of growth factors with
      the highest stimulatory responses (PDGF-IGF-I, FGF-PDGF and EGF-PDGF added
      simultaneously) to a double dose of PDGF, with the highest mean rank for the
      combination PDGF-IGF-I (p = 0.018). In conclusion, combinations such as PDGF-AB
      and IGF-I may be more useful than PDGF-AB alone for application in chronic
      diabetic wounds.

PMID- 11998868
TI  - Transmembrane cooperative linkage in cellular adhesion.
AB  - Various dynamic cellular activities require precise regulation of extracellular
      adhesion. Here we propose a simple thermodynamic model that does not depend on
      affinity regulation of transmembrane adhesion molecules but, rather, is based on
      the principles of collision-limited reactions. We show that the number of
      transmembrane adhesion molecules forming extracellular bonds depends on the
      degree of cytoskeletal damping of their lateral mobility (translational entropy)
      within the plane of the plasma membrane. This type of transmembrane cooperativity
      between cytoskeletal linkage and the number of extracellular bonds does not
      require high affinities to the cytoskeleton (micromolar range) and will be
      particularly effective at low extracellular affinities of adhesion molecules
      (millimolar range).

PMID- 11998869
TI  - Determination of the mitotic index by microinjection of fluorescently labelled
      tubulin.
AB  - The microneedle injection technique is one of the most established procedures for
      the introduction of proteins into living cells. To analyse injected proteins
      which are important in cell cycle progression it is often necessary to determine
      the mitotic index. Measuring the mitotic index after microinjection is
      complicated because only a limited number of cells of the whole cell population
      is microinjected. Therefore, we attempted to establish a new method to determine
      the mitotic index using microinjection of fluorescently labelled alpha/beta
      tubulin into mammalian cells which allows to monitor the injected cells
      simultaneously with the determination of the mitotic index. We demonstrated that
      fluorescently labelled tubulin incorporates efficiently into the mitotic spindle
      apparatus. Fluorescence remains stable for several hours which is sufficient to
      observe the progression of cells through the M-phase of the cell cycle. The
      determination of the mitotic index with the method presented here gave similar
      results to those determined using other methods. With this method also different
      stages of mitosis can be visualized by analysing various steps of spindle
      formation. Thus, this rapid method allows the monitoring of the injected cells
      after microneedle injection and simultaneously the determination of the mitotic
      index.

PMID- 11998870
TI  - Cluster of pulmonary blastomycosis in a rural community: evidence for multiple
      high-risk environmental foci following a sustained period of diminished
      precipitation.
AB  - Much of our understanding of the epidemiologic features of infection with
      Blastomyces dermatitidis has come from cluster and outbreak investigations which
      have established the association of human disease with recreational pursuits and
      the presence of infectious microfoci in areas of moist soil with high organic
      content. This report describes the clustering of eight cases of pulmonary
      blastomycosis without an apparent common source exposure which occurred during a
      90 day period in a 96 square mile area (population 4,450) within Oconto County,
      Wisconsin. We conclude that multiple high-risk environmental foci may have
      existed following a sustained five-year period of diminished precipitation in the
      cluster area. A case-control study which included family and community controls
      concluded that multiple earth-disturbing activities engaged in by case-patients
      was statistically associated with illness. Lymphocyte-proliferation assays of
      whole blood samples detected previously unrecognized infection with B.
      dermatititidis among five of 32 family controls.

PMID- 11998871
TI  - Occurrence of yeasts in psittacines droppings from captive birds in Italy.
AB  - Three-hundred twenty five droppings from parrots raised in the premises of 4
      breeders and in several private households were cultured for yeasts. One-hundred
      sixty droppings (49.2%) resulted positive. From these specimens 212 isolates
      belonging to 27 different species were obtained. Mainly Candida species such as
      C. albicans, C. catenulata, C. curvata, C. famata, C. glabrata, C. guilliermondi,
      C. holmii, C. intermedia, C. krusei, C. lambica, C. lusitaniae, C.
      membranaefaciens, C. parapsilosis, C. pelliculosa, C. sake and C. valida were
      isolated. Debarvomyces marama, D. polymorphus, Geotrichum sp., Pichia etchelsii,
      P. ohmeri, Rhodotorula glutinis, R. rubra, Rhodotorula sp., Saccharomyces
      cerevisiae, S. kluyiveri and Zygosaccharomyces sp. were also obtained. Dark
      colonies on Staib medium were never observed. The psittacine birds apparently
      serve as carriers for several Candida species or their perfect states and to a
      lesser extent for other opportunistic yeasts such as Rhodotorula, Trichosporon
      and Saccharomyces spp., which are considered part of the transient microbiota of
      the gastrointestinal tract. The most striking finding was the absence of
      Cryptococcus spp. among the isolates. The present survey confirms the role of pet
      birds in carrying potential zoonotic yeasts.

PMID- 11998872
TI  - Cell-associated collagenolytic activity by Candida albicans.
AB  - Cell associated collagenolytic activity of Candida albicans was quantified by
      measuring the degradation of synthetic peptide 2-furanacryloyl-Leu-Gly-Pro-Ala
      (FALGPA), which is a specific substrate for collagenase, by the freeze-thaw
      procedure method. This collagenolytic activity was enhanced by cells cultured in
      the presence of bovine serum albumin (BSA) in culture medium. However, this
      activity was inhibited in the presence of ethylenediaminetetraacetic acid
      disodium salt (EDTA-2Na), but not by the serine proteinase inhibitor p
      amidinophenyl methanesulfonyl fluoride (APMSF), nor the aspartyl proteinase
      inhibitor pepstatin A. These results suggested the presence of a metalloenzyme on
      pericellular C. albicans.

PMID- 11998873
TI  - Antifungal activity of 5 new synthetic compounds vs. Trichophyton rubrum and
      Epidermophyton floccosum.
AB  - The antifungal activity of five new synthetic compounds was evaluated on two
      dermatophytes: Epidermophyton floccosum and Trichophyton rubrum. The data showed
      that the imidazo-pyrazole and pyrazolo-thiazoles were not particularly effective,
      while the two pyrazole-thiocyanates proved highly active on both fungi. The most
      active 5-amino-3-methyl-1-phenylpyrazolo-4-thiocyanate was chosen to perform SEM
      and TEM morphological studies on both fungi. Both SEM and TEM observations
      revealed interesting alterations on the two dermatophytes, particularly involving
      the endomembrane system.

PMID- 11998874
TI  - Repeated isolation of Cryptococcus laurentii from the oropharynx of an
      immunocompromized patient.
AB  - Cryptococcus laurentii is one of the non-neoformans cryptococci that have rarely
      been isolated from humans. We report a case of repeated colonization of the
      oropharynx by Cr. laurentii in a patient with erythroleukaemia. The isolate was
      identified by phenotypic and genotypic tests and showed resistance to
      fluconazole.

PMID- 11998875
TI  - Observation of woronin bodies in Arthrinium aureum by scanning electron
      microscopy.
AB  - Woronin bodies are cytoplasmic organelles of filamentous fungi that can be
      observed on one, or both sides of each septum. The goal of this paper is to
      illustrate the presence of them in hyphae of Arthrinium aureum by means of
      scanning electron microscopy and to show that they act as a safety plug to close
      septa pores in hypha. Results show that Woronin bodies as an immediate response
      to prevent a cytoplasm loss. Results support hypothesis proposed previously in
      literature.

PMID- 11998876
TI  - Serological differences in two Blastomyces dermatitidis isolates from different
      geographical regions of North America.
AB  - Yeast phase lysate antigens were prepared from two isolates (T-58 and ERC-2) from
      different geographic locations. Tennessee and Wisconsin. These lysate were
      evaluated with respect to their ability to detect antibody in dogs infected with
      blastomycosis and rabbits immunized with the lysates by an enzyme linked
      immunosorbent assay (ELISA). Both the dog sera and rabbit sera assays
      demonstrated that there were serological differences in these two isolates, which
      implied that there was antigenic variance in geographical populations of B.
      dermatitidis. These results correlated with a previous molecular study that
      indicated that there are genetic differences in different geographical
      populations of the organism.

PMID- 11998877
TI  - Trichophyton violaceum is the dominant cause of tinea capitis in children in
      Tripoli, Libya: results of a two year survey.
AB  - The causative agents of tinea capitis in Libyan nationals attending the out
      patient Dermatology Clinic of the Tripoli Medical Centre over the period December
      1997 to December 1999 were investigated. Samples (hair and scalp scrapings) were
      taken from 940 patients who presented with suspected tinea capitis. The
      etiological agents were identified in 584 cases. Trichophyton violaceum was found
      to be the most prevalent organism isolated being responsible for 64.4% (376/584)
      of culture positive cases, followed by Microsporum canis at 24.7% (144/584) and
      T. mentagrophytes at 5.5% (32/584). The majority of infections (380/584) occurred
      in females and in children with ages less than 12 years (554/584).

PMID- 11998878
TI  - In vivo and in vitro electrophysiological monitoring of rat neocortical activity
      after dietary fumonisin exposure.
AB  - Corn pellets, containing 30 mg/kg bw/day fumonisin B1 (FB1) or containing no FB1
      were fed in two series of experiments to rats. Spontaneous and evoked potentials
      were measured in the neocortex both in vivo and in vitro in "corn fed control"
      rats and in rats after a five day dietary exposure to FB1. The FB1 content of
      corn was quantitated by HPLC. Auditory evoked potentials recorded in vivo on
      freely moving animals after feeding a corn diet containing FB1 for 5 days
      revealed a highly significant 20-60% decrease in the primary and mid-latency
      components; cortex slices in vitro showed a reduced excitability both in standard
      artificial cerebrospinal fluid (ACSF) solution and in a 4-aminopyridine induced
      epilepsy model. Spontaneous epileptic discharges after FB1 exposure had an
      increased latency, decreased frequency, longer duration and modified signal
      forms. Altered excitability and seizure susceptibility of the neocortex after
      fumonisin exposure are suspected to be associated with modified signal
      transmission. These changes may be due to concurrent effects of possible liver
      and renal toxicity or partly of nutritional deficiencies.

PMID- 11998879
TI  - Collagenase production in an antarctic strain of Arthrobotrys tortor Jarowaja.
AB  - This paper describes the results of a comparative screening between the
      nematophagous Antarctic fungus Arthrobotrys tortor and other species of that
      genus for the production of extracellular collagenases. The nematode species used
      in this study was Caenorhabditis elegans, feeding on Escherichia coli cultures.
      Determination of collagenase activity was made using insoluble collagen from
      bovine Achilles tendon and determining the amount of solubilized hydroxyproline
      produced. The results show that the total amount of collagenase produced by the
      Antarctic strain of A. tortor was about threefold higher than that observed for
      the other species. In the Antarctic strain, collagenase was shown to be a
      constitutive enzyme.

PMID- 11998880
TI  - Retinopathy as a predictor of other diabetic complications.
AB  - PURPOSE: Early predictors of diabetic complications may aid in the prevention
      and/or management of these complications. The aim of this cross-sectional study
      was to determine the predictive value of retinopathy for the presence of other
      diabetic complications. METHODS: The population studied comprised 648 patients
      with diabetes mellitus assessed by our service. There were 210 patients (32.4%)
      with insulin-dependent diabetes mellitus (IDDM), and 438 patients (67.6%) with
      non-insulin-dependent diabetes mellitus (NIDDM). RESULTS: Univariate analyses
      revealed that retinopathy significantly predicted the presence of neuropathy
      (odds ratio [OR] = 2.23; 95% confidence interval [CI] = 1.56-3.18; p < 0.001),
      nephropathy (OR = 5.68; 95% CI = 3.06-10.62; p < 0.001), and cerebrovascular
      disease (OR = 6.6; 95% CI = 1.16-67.21; p = 0.0239) in the total group. Similar
      associations were observed both in subjects with IDDM and NIDDM. The associations
      between retinopathy severity level and the prevalence rate of nephropathy were
      significant in the total group (p = 0.0001), in patients with IDDM (p = 0.0113),
      and in patients with NIDDM (p = 0.01). In patients with mild to moderate non
      proliferative retinopathy (NPDR), nephropathy was present in 17.2% of patients
      with IDDM, and in 11.4% of patients with NIDDM. In patients with severe NPDR,
      nephropathy was present in 23.3% in patients with IDDM, and in 11.8% of patients
      with NIDDM. In patients with proliferative retinopathy (PDR), nephropathy was
      present in 50% in patients with IDDM, and in 45.5% in patients with NIDDM. In
      multivariate logistic regression analyses, nephropathy was the only significant
      complication to be independently associated with retinopathy in patients with
      IDDM (OR = 8.02; 95% CI = 1.95-33), and in patients with NIDDM (OR = 2.48; 95% CI
      = 1.02-6.03). CONCLUSIONS: Retinopathy, especially the presence of PDR, is an
      independent predictor for nephropathy. The predictive value of retinopathy for
      nephropathy is stronger in patients with IDDM than in those with NIDDM.
      Ophthalmologists should refer patients with retinopathy for regular medical
      evaluations.

PMID- 11998881
TI  - Radiotherapy for age-related macular degeneration: is there a benefit for classic
      CNV?
AB  - AIM: To evaluate the efficacy of radiotherapy in the treatment of subfoveal
      classic and occult choroidal neovascularization (CNV) in age-related macular
      degeneration (AMD) under strict fixation control. METHODS: Twenty-seven eyes of
      27 patients with subfoveal CNV as a result of AMD were treated with a total dose
      of 20 Gy in 10 fractions (10 well-defined, 17 occult). Fixation monitoring was
      achieved by installing a TV camera with an attached fixation light 3 cm from the
      cornea of the eye being treated. Visual acuity and fluorescein angiography were
      obtained before and 6 months after treatment. Fifteen eyes of 15 patients served
      as controls (4 well-defined, 11 occult). RESULTS: After 6 months the treated
      group showed an average decrease in visual acuity of 27%; the control group
      experienced a decrease of 31%. Membrane size increased by 56% in the treated
      group and by 28% in the control group. There was no statistically significant
      difference. Within the subgroup analysis, however, patients with classic CNV
      suffered significantly less visual loss than in the control group. CONCLUSION:
      Radiation therapy under optimized treatment conditions by fixation monitoring
      failed to control further growth in membrane size in both classic and occult CNV.
      Regarding visual acuity, however, patients with classic CNV seem to benefit from
      radiation treatment compared to the natural course.

PMID- 11998882
TI  - Rhegmatogenous retinal detachment in morning glory syndrome pathogenesis and
      treatment.
AB  - We report a case of morning glory syndrome with retinal detachment. A slit-like
      retinal break at the edge of the excavated disc anomaly provided a direct
      communication between the subretinal space and the vitreous cavity. Retinal
      reattachment and useful vision was achieved after a single procedure of
      vitrectomy and gas tamponade. We believe that identification of the retinal
      break, removal of epipapillary fibroglial tissue and its traction force, the
      avoidance of perfluorocarbon liquid and the appropriate use of long-acting gas as
      endotamponade, all contributed to the favorable outcome. This is more evidence
      supporting the rhegmatogenous theory of retinal detachment in morning glory
      syndrome. A literature review of the clinical presentations and treatments of
      similar cases is included.

PMID- 11998883
TI  - Change in lens thickness after trabeculectomy.

PMID- 11998884
TI  - Retinal nerve fiber layer analysis and interpretation of GDx parameters in
      patients with tilted disc syndrome.
AB  - This study was conducted to determine abnormalities of the GDx Glaucoma Scanning
      System parameters in patients with tilted discs, in order to set guidelines for
      the evaluation of glaucomatous damage in this situation. The objective was to
      determine which GDx parameters displayed the highest level of variation, and
      which remained unchanged in tilted disc syndrome. RNFA was polarimetrically
      conducted on 45 eyes from 26 subjects with tilted discs, and 43 normal eyes with
      Nerve Fiber Analyzer II (Laser Diagnostic Technologies). All parameters except
      inferior maximum, average thickness, ellipse average, and inferior average
      displayed a significant difference between the two groups (p < 0.05). Although
      NFA is useful in glaucoma diagnosis, the majority of the GDx parameters, as shown
      in our study, are unreliable in tilted disc syndrome in this respect.

PMID- 11998885
TI  - Bone marrow transplantation retinopathy.
AB  - BACKGROUND: Bone marrow transplantion (BMT) is the treatment of choice for both
      malignant and nonmalignant disorders of the bone marrow. BMT retinopathy occurs
      after a latent period of 6 months and usually recovers after a few weeks.
      METHODS: We present a case of BMT retinopathy (BMT) in a patient with a high
      degree of non-Hodgkin lymphoma. We analysed the funduscopic and angiographic
      findings, and the evolution of the case. RESULTS AND CONCLUSIONS: After a period
      of two and a half years we observed the spontaneous complete resolution of the
      fundus lesions and the recovery of visual acuity All of this confirm the theory
      that BMT retinopathy does not progress beyond the ischemic microvascular stage.

PMID- 11998886
TI  - The evaluation of chronic progressive external ophthalmoplegia with computerized
      tomography.
AB  - INTRODUCTION: Chronic progressive external ophthalmoplegia is characterised by
      limitation of ocular motility in all directions of gaze and ptosis. Innervational
      or myogenic factors were claimed to be responsible for this motility disorder.
      The aim of this study was to investigate the extraocular muscles in CPEO with
      computerized tomography in an attempt to distinguish extraocular muscle
      morphology caused by this disorder from that occurring in normal individuals.
      METHODS: Eighteen orbits from 9 patients diagnosed with CPEO were included in the
      study. Axial and coronal scans were obtained for CT evaluation of extraocular
      muscles and the dimensions of extraocular muscles were measured. The control
      group consisted of 40 orbits belonging to 20 individuals and, the results were
      compared with a student's t test. RESULTS: The thickness (the vertical dimension
      of vertical recti and the horizontal dimension of horizontal recti) of all rectus
      muscles was significantly decreased in comparison with the control group, whereas
      the width (the horizontal dimension of vertical recti and the vertical dimension
      of horizontal recti) was similar in both the diseased and normal orbits. In all
      the rectus muscles of the diseased orbits, the normal fusiform shape was lost and
      the muscles appeared as thin bands. DISCUSSION: The differentiation of CPEO from
      other myogenic and neurogenic disorders may present difficulty, and a cluster of
      criteria are required for a final diagnosis. CT has proven to be a valuable tool
      in assessing extraocular muscles [1, 2]. In this study, an extreme atrophy of all
      rectus muscles was demonstrated by means of CT. This diagnostic method may
      consequently contribute to a proper diagnosis of CPEO.

PMID- 11998887
TI  - A case of choroidal osteoma with subsequent laser induced decalcification.
AB  - A rare benign tumor, choroidal osteoma with accompanying choroidal
      neovascularization treated with laser photocoagulation is reported. Limited
      decalcification was noted at the borders of laser photocoagulation.

PMID- 11998888
TI  - Histopathologic ocular examination after lensectomy in a Macacus rhesus monkey,
      an unexpected event of secondary glaucoma.
AB  - In a Macacus rhesus monkey an unilateral lensectomy was performed on the 15th day
      of life to study the emmetropization proces. During a period of 20.5 months
      refractional state, axial length, corneal dioptric power and intraocular pressure
      were measured in the aphakic and fellow eye. Results showed that axial elongation
      of the aphakic eye was larger in comparison to the phakic fellow eye.
      Histopathologic examination of the aphakic eye revealed glaucomatous changes due
      to obstruction in the anterior chamber angle.

PMID- 11998889
TI  - Timing of fornix reconstruction for postoperative conjunctival prolapse.
AB  - BACKGROUND AND OBJECTIVE: To describe fornix reconstruction for conjunctival
      prolapse occurring after ocular surgery. MATERIALS AND METHODS: Two patients with
      persistent conjunctival prolapse of variable duration following ocular surgery
      underwent fornix reconstruction using the method described by Barrett. The two
      patients underwent different surgical methods. In the second patient, no attempt
      was made to include the malar periosteum. RESULTS: Case 1 with longer duration of
      prolapse needed further surgery to excise residual prolapsing conjunctiva that
      had hyperplastic squamous epithelium. Case 2 in which fornix reconstruction was
      done 2 months after prolapse showed a good result after only one surgical
      operation. CONCLUSION: Forniceal reconstruction is recommended for persistent
      postoperative conjunctival prolapse. Early surgery appears to have better
      results.

PMID- 11998890
TI  - Causes of childhood blindness in Malaysia: results from a national study of blind
      school students.
AB  - A national study was conducted in children attending six schools for the blind in
      Malaysia to identify the anatomical site and underlying causes of blindness (BL)
      and severe visual impairment (SVI), with a view to determine the potentially
      preventable and treatable causes so that appropriate control measures can be
      implemented in the future. The standardized clinical examination of eyes was
      performed and the findings were recorded on the WHO Prevention of Blindness
      Programme eye examination record form for children with blindness and low vision.
      A total of 358 children aged between 7 and 17 years were examined, of whom 332
      (92.7%) were blind or severely visually impaired. The results relate to these 332
      children. Lens was the major anatomical site (22.3%) of visual loss followed by
      retina (20.8%), whole globe (17.2%), cornea (15.1%), optic nerve (8.7%) and uvea
      (5.1%). Glaucoma was responsible for BL/SVI in 7.2% and others in 3.6% of cases.
      Hereditary diseases were responsible for visual loss in 29.5%, intrauterine
      factors in 4.5%, perinatal factors in 9% and childhood factors in 7.8% of cases.
      However, the aetiology was unknown in 49.1% of cases which included congenital
      anomalies of the globe. Childhood cataract and corneal scarring are major
      treatable causes of BL/SVI that can benefit from future intervention strategies.
      Perinatal screening for intrauterine factors and hereditary eye diseases, and
      appropriate interventional therapy will help in reducing the prevalence of
      childhood blindness.

PMID- 11998891
TI  - Plasma and salivary IgA subclasses and IgM in HIV-1-infected individuals.
AB  - We examined IgA and IgM responses in parotid saliva from human immunodeficiency
      virus-1 (HIV-1)-infected individuals. Compared to the uninfected controls, levels
      of salivary secretory IgA2 were significantly increased in HIV-1-infected
      subjects, with higher levels in those who displayed oral manifestations of HIV- I
      infection. Assessed by enzyme immunoassay, about two thirds of the HIV-1-infected
      individuals tested positive for salivary HIV-1-specific IgA antibodies but not
      for salivary IgM. No clear correlations between the amount of HIV-1-specific IgA
      and CD4 counts or plasma viral loads were found. The proportions of HIV-1
      specific IgA did not correlate with the levels of total IgA. Determined by
      Western blot, IgA1 accounted for the majority of anti-HIV-1 IgA antibodies in
      saliva. Comparisons between the specificities of plasma and salivary IgA directed
      to HIV-1 proteins revealed the absence of salivary anti-gp41 IgA antibodies, and
      lower HIV-1-specific reactivity of IgA and IgM were determined in saliva than in
      plasma.

PMID- 11998892
TI  - The IL-2/IL-15 receptor systems: targets for immunotherapy.
AB  - Although interleukin-2 (IL-2) and -15 (IL-15) share two receptor subunits and
      many functions, at times they provide contrasting contributions to T-cell
      mediated immune responses. IL-2, through its pivitol role in activation-induced
      cell death (AICD), is involved in peripheral tolerance through the elimination of
      self-reactive T cells. In contrast, in general IL-15 manifests antiapoptotic
      actions and inhibits IL-2-mediated AICD. IL-15 stimulates persistence of memory
      phenotype CD8+ T cells, whereas IL-2 inhibits their expression. Humanized
      monoclonal antibodies that recognize IL-2Ra, the private receptor for IL-2, are
      being employed to inhibit allograft rejection and to treat T-cell
      leukemia/lymphoma. Therapies directed toward inhibiting the actions of the
      inflammatory cytokine, IL-15, are proposed for an array of autoimmune disorders
      as well as diseases associated with the retrovirus human T-cell lymphotrophic
      virus 1.

PMID- 11998893
TI  - Genetic instability of adult T-cell leukemia/lymphoma by comparative genomic
      hybridization analysis.
AB  - Adult T-cell leukemia/lymphoma (ATL) is a distinct clinicopathological entity,
      i.e., peripheral T-lymphocytic malignancy caused by human T-lymphotropic virus
      type I (HTLV-1) with diverse clinical features. High frequency of genetic
      instability (GIN) in both aggressive and indolent ATL was detected by comparative
      genomic hybridization (CGH). Among GIN, chromosomal instability, i.e.,
      ancuploidy, in indolent ATL was as frequent but less complex and dynamic as
      compared to those in aggressive ATL. Some of the CGH alterations, including gain
      of 14q32, appear to be rather ATL specific. Clonal instability of HTLV-1-infected
      T cells. i.e., emergence of distinct clone, was detected in about one forth of
      acute crisis from indolent ATL by CGH and Southern blotting for HTLV-1. Taking
      together with the previous reports of frequent subtle mutations in several tumor
      suppressor genes in aggressive ATL, GIN in multistep leukemogenesis of ATL is
      diverse including clonal, chromosomal, and nucleotide levels.

PMID- 11998894
TI  - Treatment of leukemia by alloreactive lymphocytes and nonmyeloablative stem cell
      transplantation.
AB  - Allogeneic bone marrow or blood stem cell transplantation (BMT) represents an
      important therapeutic tool for treatment of otherwise incurable malignant and
      nonmalignant diseases, especially acute and chronic leukemias. Until recently,
      myeloablative regimens were considered mandatory for effective eradication of all
      malignant cells of host origin. Our preclinical and ongoing clinical studies
      indicated that eradication of host immunohematopoietic cells, including
      chemoradiotherapy-resistant leukemia, could be achieved by adoptive allogeneic
      cell therapy with donor lymphocyte infusion following induction of host-versus
      graft transplantation tolerance mediated by engraftment of donor stem cells in
      the course of BMT. Thus, eradication of blood cancer cells, especially in
      patients with chronic myeloid leukemia and less frequently in patients with other
      hematologic malignancies, could be frequently accomplished despite complete
      resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy.
      Our cumulative experience suggested that graft-versus-leukemia (GVL) effects
      might be a useful tool for both treatment and prevention of relapse. Based on the
      aforementioned rationale, we speculated that the therapeutic benefit of BMT may
      be improved by using a safer conditioning as part of the transplant procedure,
      with the goal in mind to induce host-versus-graft tolerance to enable subsequent
      induction of GVL effects rather than attempt to eliminate host cells with
      hazardous myeloablative chemoradiotherapy. The latter hypothesis suggested that
      effective BMT procedure may be accomplished without lethal conditioning of the
      host, using a new well-tolerated nonmyeloablative regimen, thus possibly
      minimizing immediate and late side effects related to myeloablative procedures
      considered until recently mandatory for conditioning of BMT recipients. Recent
      clinical observations suggest that effective treatment of leukemia may be
      accomplished with a well-tolerated nonmyeloablative stem cell transplantation
      (NST) regimen, while avoiding immediate and late toxicity and minimizing
      procedure-related mortality. Taken together, our cumulative data suggest that
      high-dose chemotherapy and radiation therapy may be successively replaced by a
      more effective biological tool-alloreactive donor lymphocytes-thus setting the
      stage for innovative immunotherapeutic procedures for more selective and
      effective treatment of patients in need of BMT, including those resistant to
      conventional chemoradiotherapy.

PMID- 11998895
TI  - Nonmyeloablative hematopoietic cell transplantation: status quo and future
      perspectives.
AB  - In nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT),
      high-dose cytotoxic therapy as the conceptual basis for treating hematopoietic
      malignancies has been replaced by graft-versus-tumor effects. The use of potent
      pre- and postgrafting immunosuppression derived from preclinical studies has
      allowed omission of myeloablative cytotoxic therapy without compromising
      hematopoietic donor cell engraftment. This results in a marked reduction in
      transplant-related toxicities that makes older or medically infirm patients
      candidates for this treatment option. This patient group is more representative
      of the population with cancer and would have been ineligible for conventional
      HSCT. Initial results in patients with a variety of hematologic malignancies have
      been encouraging with documented sustained cytogenetic and molecular remissions
      in a substantial number of sometimes heavily pretreated and previously refractory
      patients. Even though patients with hematologic malignancies will likely require
      conversion to full donor hematopoiesis for long-term disease control, a state of
      mixed hematopoietic chimerism might suffice to "cure" the disease phenotypes in
      various nonmalignant diseases. Strategies aimed at optimizing peritransplant
      immunosuppression may eventually eliminate the need for pretransplant total body
      irradiation, which is relevant for minimizing late toxicities. Enhancing graft
      versus-tumor effects by virtue of postgrafting vaccination of recipients against
      tumor-specific antigens may help to use this transplant approach more effectively
      in the treatment of solid tumors.

PMID- 11998896
TI  - Correlations of soluble interleukin-2 and tumor necrosis factor type II receptors
      with immunologic and virologic responses under HAART.
AB  - We assessed the correlations between some plasma markers of immune activation
      (soluble receptors of interleukin 2 (sIL2-R) and TNFap75 (sTNFII-R) and usual
      markers of HIV infection in patients treated with protease-inhibitors (PI). Forty
      six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort
      from the initiation of a P1-containing regimen (M0). Measurements of CD4+cell
      count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The
      evolution of sIL2-R from baseline to M12 was significantly different between
      immunological responders (IR) (CD4+count above 200/mm3 for subject having less
      than 200 CD4 +/mm3 at inclusion, or increase of at least 50 CD4+/mm3 for others)
      (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0
      and M12 was significantly different between virological responders (VR) (plasma
      HIV-1 RNA less than 500 copies/ml at M12) (-2.5 ng/ml) and non-VR (+0.2 ng/ml) (P
      = 0.02). Our study shows significative correlations between the evolutions of
      soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV
      RNA responses in patients under HAART.

PMID- 11998897
TI  - Oral administration of gammalinolenic acid, an unsaturated fatty acid with anti
      inflammatory properties, modulates interleukin-1beta production by human
      monocytes.
AB  - Administration of gammalinolenic acid (GLA), an unsaturated fatty acid, reduces
      joint inflammation in patients with rheumatoid arthritis. Addition of GLA in
      vitro suppresses release of interleukin-1beta (IL-1beta) from human monocytes
      stimulated with lipopolysaccharide (LPS). LPS-induced IL-1beta release is
      followed by IL-1-induced IL-1beta release, an amplification process termed
      "autoinduction." We show here, using IL-1alpha stimulation to simulate
      autoinduction, that administration of GLA to healthy volunteers and to patients
      with inflammatory arthritis reduces LPS-induced IL-1beta secretion mainly by
      reducing autoinduction of IL-1beta. GLA reduces LPS-induced pro-IL-1beta mRNA
      modestly and IL-la-induced pro-IL-1beta gene expression markedly. In addition to
      reducing amplification of IL-1beta, GLA increases the amount of IL-1 receptor
      antagonist (IL-1Ra) secreted from stimulated cells, thereby facilitating an
      increase in the secreted IL-1Ra/IL-1beta ratio. IL-1beta is important to host
      defense, but the amplification mechanism may be excessive in genetically
      predisposed individuals. Thus, reduction of IL-1beta autoinduction may be
      protective in some patients with endotoxic shock and with diseases characterized
      by chronic inflammation.

PMID- 11998898
TI  - Serum IgG2 concentration is associated with Gm-allotypes of IgG2 but not with the
      R131H polymorphism of human Fc-gamma receptor type IIa.
AB  - Serum concentrations of immunoglobulins IgG, IgG1, and IgG2 were determined in 62
      Finnish subjects who were also typed for Gm(n) allele of IgG2 and R131 and H131
      alleles of the Fcy receptor IIa. Statistically significant G2m-allotype
      associated differences in serum concentrations of IgG2 were found; the mean
      concentration of IgG2 was high in Gm(n)-positive homozygotes (3.9 g/liter) and
      low in Gm(n)-negative individuals (2.6 g/liter; P = 0.0036), which is in
      accordance with previous reports. Contrary to an earlier report, no statistically
      significant R131/ H131-allotype-associated differences were found in serum
      concentrations of IgG2, not even in the case where the IgG2 concentration was
      calculated relative to the IgGI or IgG concentration (IgG2/IgG1 or IgG2/IgG). The
      gene frequencies of R131 and H131 alleles were 0.516 and 0.484, respectively,
      which did not differ significantly from those reported earlier for Finnish or
      other Caucasian populations.

PMID- 11998899
TI  - Autoantibody responses in Chinese hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and
      is particularly prevalent in Henan, China. The objective of this study was to
      analyze the frequency and specificity of autoantibodies associated with HCC in
      Henan. In the present study, 137 sera from HCC patients, 77 sera from other liver
      diseases, and 30 sera from normal human individuals were examined for
      autoantibodies using immunohistochemistry, Western blotting, and
      immunoprecipitation assays. Autoantibodies were detected in 80 of 137 (58.4%) HCC
      sera. Antinucleolar antibodies were seen more frequently in HCC compared to other
      liver diseases (9.5% vs. 1.3%, P < 0.05). Two nucleolar proteins-fibrillarin and
      NOR-90/ hUBF-were identified as autoantigens. The frequency of autoantibodies in
      HCC sera with known hepatitis C virus (HCV) infection was significantly higher
      than that in sera without HCV infection (84.2% vs. 57.7%, P < 0.01). Another
      interesting finding was that autoantibodies to a 90-kDa cytoplasmic antigen were
      found in 21% of HCC patients. This is the first report on the frequency and
      specificity of autoantibodies in sera from Chinese patients with HCC. The data
      support that autoimmune responses to certain cellular proteins may be a by
      product in the transformation to HCC, and further studies of novel targeted
      autoantigens in Chinese HCC may provide insights into how these proteins might be
      involved in malignancy.

PMID- 11998900
TI  - Evaluation of demineralized dentin contraction by stereo measurements using
      environmental and conventional scanning electron microscopy.
AB  - Numerous investigations of etched human dentin are performed using scanning
      electron microscopy (SEM). Usually specimens are fractured and cross sections of
      etched layers with underlying unaffected dentin are observed. Results from this
      study showed that the edge of the etched layer contracted and became curved after
      fracture of wet specimens and that tensile stresses were developed in this layer
      by acid etching. The degree of contraction was determined utilizing profiles of
      the specimen edges obtained with the help of stereo measurements. Fixation in
      glutaraldehyde decreased the contraction in wet specimens prepared for
      environmental scanning electron microscopy (ESEM). Fixation also decreased
      shrinkage of the demineralized layer due to gradual desiccation in the ESEM
      during observation. For conventional SEM, the contraction was minimized if
      specimens of etched and fixed dentin were fractured in the dry condition after
      dehydration.

PMID- 11998901
TI  - Case study--Resolution Sciences Corporation, Inc.

PMID- 11998902
TI  - Cosmetic assessment of the human hair by confocal microscopy.
AB  - The optical sectioning property of the confocal microscope offers a breakthrough
      from the classic observation of the hair in a scanning electron microscope (SEM).
      Confocal microscopy requires minimal sampling preparation, and the hair can be
      observed in its natural environment with less damage than by other microscopic
      methods such as SEM. While used in the reflection mode, the true morphology of
      the cuticle and the various exogenous deposits at the surface can be identified
      and quantified. This relatively noninvasive, nondestructive technique is
      routinely used by us to monitor the efficiency of cleansing shampoos, to assess
      the homogeneity of layering polymers, and to evaluate the changes they induce in
      the optical properties of the hair surface in terms of opacity, transparency, and
      brilliancy. A second important field of investigation uses the fluorescence
      channel which reveals the internal structure of the hair. Fluorescent probes
      (rhodamine and its derivatives) demonstrate the routes of penetration and outline
      the geometry of cortical cells and of the medulla according to their lipophilic
      or hydrophilic properties. A volume rendering of a hair cylinder provides a
      better understanding of the interrelationships between cuticle cells, cortical
      cells, and the medullar channel. This recent technology is becoming an invaluable
      tool for the cosmetic assessment of the hair.

PMID- 11998903
TI  - The method for the reconstruction of complex images of specimens using
      backscattered electrons.
AB  - The backscattered electron signal (BSE) is widely used for investigation of
      specimen surfaces in a scanning electron microscope (SEM). The development of
      multiple detector systems for BSE signal detection and the methods of digital
      processing of these signals have allowed for reconstruction of the third
      dimension on the basis of the two-dimensional (2-D) SEM image. A technique for
      simultaneous mapping of material composition (COMPO mode) and reconstruction of
      surface topography (TOPO mode) has also been proposed. This method is based on
      the measurements of BSE currents sensed by four semiconductor detectors versus
      the inclination angle of surface. To improve the separation of topographic and
      material contrasts in SEM, a correction of the TOPO and COMPO modes (resulting
      from a theoretical description of the system: electron beam, specimen, and
      detector) was applied. The proposed method can be used for a correct
      reconstruction of the surface image when the surface slope is <60 degrees. The
      measuring limit of the slope was closely connected with the detector setup. Next,
      the digital simulation of the colors was performed (after application of the
      method of linearization of BSE characteristic versus atomic number). This
      procedure to increase the SEM resolution for the BSE signal by use of digital
      image processing allows for a better distinction between the two elements with
      high atomic numbers.

PMID- 11998904
TI  - Energy distribution of electron backscattering from crystals and relation to
      electron backscattering patterns and electron channeling patterns.
AB  - This paper reports on the influence of the channeling effect on the energy
      distribution of electrons backscattered from crystals with different atomic
      numbers Z. These results can be used for the optimization of the contrast of
      electron backscattering and electron channeling patterns. Energy and angular
      resolved electron scattering distributions are obtained using a 4-axial
      experimental setup with a moveable high-resolution spherical spectrometer.
      Special care is taken to suppress undesired reflections of electrons inside the
      spectrometer. This experimental setup allows the direct observation of the
      excitation of different Bloch waves (anomalous absorption and transmission)
      within the crystal for different electron incidence angles and the observation of
      angular distributions of elastically scattered electrons. Results are presented
      for Si and Au monocrystals, showing that the influence of the channeling effect
      is more distinct for low atomic numbers.

PMID- 11998905
TI  - Conditions for imaging emulsions in the environmental scanning electron
      microscope.
AB  - Environmental scanning electron microscopy (ESEM) is a technique capable of
      imaging volatile and/or insulating samples in their natural state, without prior
      specimen preparation. It is thus a powerful potential tool for the study of the
      structure and dynamics of emulsions and other complex liquid systems, at a
      resolution greater than that obtainable by conventional optical microscopy. We
      present images of a variety of liquid systems containing micron-scale and smaller
      features. The morphology of these systems may be clearly discerned. The contrast
      observed between the liquid phases was consistent with the model proposed by
      Stokes et al. (1998). The limits of resolution were determined by sample motion
      and by beam damage effects; under optimum conditions, resolution of a few tens of
      nanometers was obtained. This compares favourably with conventional and confocal
      optical microscopy. In some samples, thin films (solid or liquid) could be
      observed at the liquid/gas interface. Some of these films were so thin that they
      did not completely obscure the underlying structure of the bulk sample.

PMID- 11998906
TI  - Automatic integrated circuit die positioning in the scanning electron microscope.
AB  - In scanning electron microscope (SEM)-based integrated circuit (IC) failure
      analysis, there is often a need for manual location of a prespecified failure
      site in several ICs. Such a procedure is both tedious and time consuming. This
      paper presents a new vision-based die positioning system that can automatically
      locate a specified failure site without the need for a high-accuracy specimen
      stage. Depending on the appearance of the desired failure site, the system
      applies either image registration or feature tracking to locate the site.
      Experiments performed on a variety of IC samples show that the system is able to
      locate the failure site accurately, even in the presence of unfavorable
      conditions such as IC sample rotation and repetitive IC patterns.

PMID- 11998907
TI  - Automated analysis of submicron particles by computer-controlled scanning
      electron microscopy.
AB  - Automated analysis of submicron particles by computer-controlled scanning
      electron microscopy is generally possible. The minimum diameter of the detectable
      particles is dependent on the mean atomic number of the particles and the
      operating parameters of the scanning microscope. The main limitation with regard
      to particle size is set by the quality of the particle detection system, which
      generally is the backscatter electron detector. The accuracy of the results of
      the x-ray analyses is very often strongly affected by specimen damage,
      omnipresent especially for environmental particles even at low electron energies
      and probe currents. With the exception for light elements, the detection limit is
      approximately 1 wt%. Device-related limitations to automated analysis may be
      specimen drift and an unreliable autofocus function.

PMID- 11998908
TI  - Cerebrospinal fluid levels of cytokines and soluble tumour necrosis factor
      receptor in acute disseminated encephalomyelitis.
AB  - We determined the concentrations of interleukin-1beta (IL-1beta, IL-6, IL-10,
      interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and
      soluble TNF receptor 1 (sTNFR1) in CSF from 18 patients with acute disseminated
      encephalomyelitis (ADEM) to investigate the role of cytokines in the pathogenesis
      of the disease in the acute stage. Cytokines and sTNFR1 were measured by ELISA.
      The CSF IL-6, IL-10, TNF-alpha, and sTNFR1 concentrations were elevated in 16,
      13, 3, and 11 of the 18 patients with ADEM, respectively. CSF concentrations of
      IL-10 and sTNFRI correlated positively with each other in the patients (P<0.01).
      Myelin basic protein levels in CSF of the patients with elevated CSF sTNFR1
      levels were significantly higher than those in CSF of the patients with normal
      CSF sTNFR1 levels (P<0.05). IL-1beta and IFN-gamma were not elevated in CSF. Our
      results suggest that IL-6 and TNF-alpha mediate inflammation in the central
      nervous systems in ADEM. We speculated that TNF-alpha is related to demyelination
      and that IL-10 is induced to modulate TNF-alpha-induced inflammation in ADEM.
      CONCLUSION: these findings suggest that cytokines such as tumour necrosis factor
      alpha, soluble tumour necrosis factor receptor 1, interleukin-6, and interleukin
      10 are related to the pathogenesis of acute disseminated encephalomyelitis in the
      acute stage.

PMID- 11998909
TI  - Tuberculous pericarditis in an infant evolving during triple chemotherapy.
AB  - A 36-month-old girl was treated for pulmonary tuberculosis (Mycobacterium
      tuberculosis) with isoniazid, rifampin and pyrazinamide. Four weeks after
      starting chemotherapy, she developed high fever and clinical signs of acute
      pericardial tamponade. Pericardial effusion was shown by echocardiography and
      subsequently removed by pericardiocentesis. M. tuberculosis was demonstrated in
      the pericardial fluid by microscopy, polymerase chain reaction and specific
      culture. After pericardial drainage, the actual therapy was extended to include
      streptomycin and prednisone. Follow-up examinations demonstrated complete
      recovery without signs of constrictive pericarditis. CONCLUSION: infants treated
      for tuberculosis should be followed closely in order to monitor not only side
      effects of antituberculous drugs but also to detect early extrapulmonary spread
      that may occur even with adequate chemotherapy. Rapid intervention and treatment
      adjustment in infants with tuberculous pericarditis may prevent pericardial
      constriction and may lead to full recovery.

PMID- 11998910
TI  - Long-term clinical effectiveness of an acellular pertussis component vaccine and
      a whole cell pertussis component vaccine.
AB  - The objective of this open study was to monitor the long-term effectiveness of
      the Lederle-Takeda diphtheria and tetanus toxoids and acellular pertussis
      antigen(s) (DTaP) vaccine and the Wyeth-Lederle diphtheria and tetanus toxoids
      and pertussis whole cell (DTP) vaccine in children who had received four doses of
      vaccine at 3, 4.5, 6 and 15 months of age during a pertussis vaccine efficacy
      trial from May 1991 to December 1994. After unblinding of the study code, follow
      up information was obtained by use of standardised questionnaires twice a year
      from 1995 to 2000 to detect clinical pertussis and cough illnesses > or = 14 days
      duration. Physician confirmation was sought for all reported cases. Rates of
      reported cough illnesses > or = 14 days duration and rates of parent and
      physician diagnosed pertussis in former DTaP, DTP and diphtheria and tetanus
      toxoids (DT) recipients were determined and vaccine efficacy was calculated. Nine
      questionnaires were sent to parents of 2924 study children of whom 349, 1304 and
      1271 had originally received DT, DTaP and DTP, respectively. Overall, rates for
      cough illnesses (per 100 person years) were similar among the vaccine groups
      suggesting that reporting bias was not a major factor. Calculated efficacy for
      the 6-year follow-up period based upon physician diagnosed pertussis was 89% (95%
      CI=79 94) for DTaP and was 92% (95% CI=84-96) for DTP. CONCLUSION: no evidence of
      decreasing efficacy over time was noted.

PMID- 11998911
TI  - Acute rheumatic fever in a patient with glycogen storage disease type Ib: causal
      or coincidental simultaneous occurrence?
AB  - We report a Caucasian female who was diagnosed with glycogen storage disease type
      Ib (GSD-Ib) at the age of 4 months and whose clinical course was complicated by
      neutropenia and very frequent episodes of infection, including
      tonsillopharyngitis. Recurrent group A streptococcal infections resulted in
      multiple episodes of extremely high serum levels of antibodies to streptolysin O
      (5,000 IU/ml) and DNAse B (6,000 IU/ ml). At the age of 14 years she presented
      with carditis, migratory arthritis, fever, elevated erythrocyte sedimentation
      rate as well as serological evidence for recent streptococcal infection providing
      a diagnosis of acute rheumatic fever. CONCLUSION: the occurrence of these two
      very rare disorders in our patient may indicate that this association is not
      coincidental because neutrophil dysfunction in glycogen storage disease type Ib
      may have predisposed this patient to acute rheumatic fever due to increased
      susceptibility to group A streptococcal infections. aberrant glycogenolysis and
      gluconeogenesis, neutropenia and neutrophil dysfunction are regular findings in
      GSD-Ib. Neutropenia and neutrophil dysfunction in patients with GSD-Ib are due to
      defects in myeloid maturation, impaired neutrophil motility, defective chemotaxis
      and phagocytosis and diminished bactericidal activity resulting in recurrent
      bacterial infections.

PMID- 11998912
TI  - The effectiveness of octreotide in the treatment of post-operative chylothorax.
AB  - Chylothorax may be spontaneous or a complication of thoracic surgery. Treatment
      of this potentially harmful condition is not well established and may comprise
      dietary interventions and surgery. Somatostatin seems effective in the management
      of chylothorax, although its mechanism of action is unclear. CONCLUSION:
      octreotide, a somatostatin analogue, may be effective in the treatment of post
      operative chylothorax.

PMID- 11998913
TI  - Growth, developmental milestones and health problems in the first 2 years in very
      preterm infants compared with term infants: a population based study.
AB  - The outcome of very preterm infants varies widely from centre to centre and from
      country to country. The aim of this study was to evaluate growth, developmental
      milestones and post-discharge morbidity of infants born before 32 weeks of
      gestation in Switzerland. A questionnaire was sent to the parents of 456
      survivors born in 1996. A total of 309 (68%) parents responded and their infants
      were matched with 309 control infants born at term. At the corrected age of 24
      months, the very preterm infants had significantly lower weight (-1.0 z-scores),
      lower length (-1.23 z-scores), and lower head circumference (-.64 z-scores). Very
      preterm infants were reported to eat with a spoon later than those born at term
      (50% at 7.5 months corrected for prematurity versus 10 months. P<0.001), to drink
      later out of a cup (50% at 16.5 months versus 13.5 months, P=0.03) and to walk
      later independently (50% at 14.5 months versus 13.5 months, P=0.04), whereas
      timing of sitting unsupported was no different (50% at 7.4 months versus 7.2
      months, P=0.9). Of very preterm infants, 16% were not able to walk at least three
      steps unsupported at 18 months after term which puts them at an increased risk
      for cerebral palsy. Some 35% of very preterm infants had to be readmitted to
      hospital during the first 24 months compared with 20% of control infants born at
      term (P<0.05). There was no difference between very preterm and term infants in
      respect to episodes of fever > 38.5 degrees C, episodes of coughing > 3 days and
      treatment with antibiotics. CONCLUSION: these data based on a national survey
      allow to quantify growth retardation, developmental delay and post-discharge
      health problems within the first 2 years in preterm infants born before 32(0)/7
      weeks.

PMID- 11998914
TI  - Congenital hemihypertrophy and pheochromocytoma, not a coincidental combination?
AB  - We describe a 19-year-old female, known to have congenital hemihypertrophy, who
      presented with bilateral benign pheochromocytoma. This is the second time that
      this combination has been reported in the literature. We speculate that the
      combination of congenital hemihypertrophy and pheochromocytoma is not
      coincidental and could be part of the clinical spectrum of the Beckwith-Wiedemann
      syndrome. CONCLUSION: in patients with congenital hemihypertrophy, the physician
      should be aware of the symptoms of pheochromocytoma. Besides screening for
      abdominal tumours, analysis of plasma and/or urinary catecholamines and/or their
      metabolites should be considered.

PMID- 11998915
TI  - Acute myeloid leukemia presenting with diabetes insipidus.
AB  - A central diabetes insipidus should be considered as a sign of primary CNS
      involvement in patients with acute myeloid leukemia even in the case of normal
      cerebrospinal fluid and magnetic resonance imaging findings.

PMID- 11998916
TI  - Hyperammonaemic encephalopathy in a 13-year-old boy.

PMID- 11998917
TI  - Epidemiology of Streptococcus pneumoniae pharyngeal carriage among healthy
      Turkish infants and children.

PMID- 11998918
TI  - Children with profound biotinidase deficiency should be treated with biotin
      regardless of their residual enzyme activity or genotype.

PMID- 11998919
TI  - Cerebellar hypoplasia, hypergonadotrophic hypogonadism, retinitis pigmentosa,
      alopecia, microcephaly, psychomotor retardation, and short stature: "D-CHRAMPS
      syndrome".
AB  - We here report a rather novel syndrome of dysmorphic features, short stature,
      microcephaly, alopecia, psychomotor retardation, retinitis pigmentosa and
      secondary amenorrhoea. This may present a new complex multisystem disorder
      distinct from those reported in the literature and we propose the acronym D
      CHRAMPS for this novel disorder.

PMID- 11998920
TI  - Familial 22q11.2 deletion: an infant with interrupted aortic arch and DiGeorge
      syndrome delivered from by a mother with tetralogy of Fallot.
AB  - When a mother with tetralogy of Fallot has a conotruncal anomaly face, her child
      might have a 22q11.2 deletion and severe congenital heart disease.

PMID- 11998921
TI  - Clinical heterogeneity in eyelid myoclonia, with absences, and epilepsy.
AB  - Eyelid myoclonia with absences should always be considered in the investigation
      of children with epilepsy.

PMID- 11998922
TI  - Mydriasis due to self-administered inhaled ipratropium bromide.
AB  - Mydriasis due to ipratropium bromide has previously been described in children
      and adults. Children as young as 4 years of age may attempt to self-administer
      their inhalers. This possibility should be considered if an asthmatic child
      presents with abnormal neurological signs.

PMID- 11998923
TI  - Fine structure of the eggs of Anopheles (Anopheles) punctimacula.
AB  - The egg of Anopheles (Anopheles) punctimacula is described from scanning electron
      micrographs. Eggs of An. punctimacula are boat shaped, with lateral floats
      extending 70% of the length of the egg. Plastronlike polyhedral chorionic cells
      with distinctive boundaries and round tubercles in the cell field cover the
      dorsal, lateral, and ventral surfaces. Narrow decks enclosing a field of
      irregular jagged tubercles and 2-4 lobed tubercles are present at both egg poles.

PMID- 11998924
TI  - The eggs of Anopheles galvaoi and Anopheles evansae, two species of the subgenus
      Nyssorhynchus.
AB  - The ultrastructure of the eggs of Anopheles (Nyssorhynchus) galvaoi Causey,
      Deane, and Deane and Anopheles (Nyssorhynchus) evansae (Brethes) are described
      and illustrated with scanning electron micrographs. The eggs of these species are
      similar to those of Anopheles (Nyssorhynchus) aquasalis Curry, Anopheles
      (Nyssorhynchus) oswaldoi (Peryassu), and Anopheles (Nyssorhynchus) konderi Galvao
      and Damasceno in having floats long, widely joined posteriorly on the dorsal
      surface, the frill encircling the anterior end of the egg, and the crown absent.
      A few distinctive characters to distinguish An. evansae from An. galvaoi are
      given.

PMID- 11998925
TI  - A comparative analysis of the ventral brush and its attachment to segment X of
      fourth-stage larvae in tribe Aedini (Diptera: Culicidae).
AB  - A comparative anatomical analysis of the ventral brush and its attachment to
      segment X of 4th-stage larvae was conducted for the genera and subgenera in tribe
      Aedini. Four types and 18 subtypes are recognized and examples of each are
      described and illustrated. A key distinguishing the types and subtypes is
      included. Some comments concerning the phylogenetic utility of the ventral brush
      are provided.

PMID- 11998926
TI  - Simultaneous detection of three mosquito-borne encephalitis viruses (eastern
      equine, La Crosse, and St. Louis) with a single-tube multiplex reverse
      transcriptase polymerase chain reaction assay.
AB  - Three mosquito-borne human encephalitis viruses (eastern equine encephalitis
      virus [EEE], St. Louis encephalitis virus [SLE], and La Crosse encephalitis virus
      [LAC]) are sympatric in the southeastern United States. However, little is known
      concerning the temporal and spatial pattern of the distribution of these viruses
      in this area. As part of surveillance activities to detect the transmission of
      these 3 viruses in the Tennessee Valley area, we developed a single-tube
      multiplex reverse transcriptase polymerase chain reaction (RT-PCR) assay capable
      of detecting these 3 mosquito-borne viruses in a single reaction. Three viruses
      were differentiated by size of amplified products. Sensitivities of the multiplex
      RT-PCR assay for SLE, EEE, and LAC were 1-3 log median tissue culture infective
      doses per pool, roughly comparable to the reported sensitivity of PCR detection
      assays for the individual viruses, and 1 log more sensitive than antigen-capture
      assays for SLE and EEE. The sensitivity of the multiplex PCR was not changed
      significantly when carried out in the presence of extracts prepared from 50
      uninfected mosquitoes. The cost of the assay is estimated at $2.98 per test,
      similar to the cost of other RT-PCR-based assays for viruses. However, adaptation
      of the RT-PCR to a multiplex format adds less than $0.01 to the per-unit cost of
      an RT-PCR assay targeting a single virus species. Analysis of these data suggests
      that the single-tube multiplex RT-PCR assay represents a sensitive, specific,
      cost-effective, and rapid method for monitoring activities of the 3 endemic
      mosquito-borne human encephalitis viruses in mosquito populations in the
      southeastern United States.

PMID- 11998927
TI  - Mark-recapture studies of host selection by Anopheles (Anopheles) vestitipennis.
AB  - We present herein the results of a series of mark-recapture experiments with
      female Anopheles vestitipennis. Theses experiments used human and animal hosts to
      assess the degree of anthropophily of field-caught specimens, originally
      collected on either host, and of their offspring. Fidelity of mosquitoes to
      particular hosts was estimated by recapturing marked host-seeking mosquitoes
      returning for a 2nd blood meal. Results indicated that mosquitoes seeking animal
      hosts were more faithful (80.48%; 33 of 41) in returning to their original host
      than were those seeking human hosts (63%; 49 of 78).

PMID- 11998928
TI  - Field trial efficacy of Anvil 10+10 and Biomist 31:66 against Ochlerotatus
      sollicitans in Delaware.
AB  - Anvil 10+10 (hereafter Anvil) and Biomist 31:66 (hereafter Biomist) were applied
      by ground ultra-low volume (ULV) methods to determine the effectiveness of each
      formulation against Ochlerotatus sollicitans. Each formulation was tested at 50,
      67, and 100% of respective maximum label dosage rates. Mosquitoes were exposed in
      cages on a 3 x 3 grid at distances of 30.5, 60.9, and 91.4 m. Mortality data were
      collected at intervals of 1, 4, and 12 h after treatment. No significant
      differences (P > or = 0.05) were found among formulations at applications of 100%
      of the label rate and no significant differences (P > or = 0.05) were found
      between Anvil applied at 100% of the label rate and Biomist applied at 50 and 67%
      of label rates. Ground ULV applications of Anvil at 100% label rate and Biomist
      at all tested rates were effective (> or = 95% mortality) adulticides.
      Applications of Anvil at 50 and 67% label rates were significantly less effective
      (P < or = 0.05) than applications of Biomist at equal percentages of the maximum
      label rate. Applications of Anvil at rates of 50 and 67% were not effective.

PMID- 11998929
TI  - An inexpensive intervention for the control of larval Aedes aegypti assessed by
      an improved method of surveillance and analysis.
AB  - A sampling method coupled with statistical calibration factors was developed to
      accurately assess the numbers of larvae and pupae of Aedes aegypti in large water
      storage containers of variable capacities and water levels. Aedes aegypti
      productivity in different types of breeding sites found in an urban study area in
      central Colombia was assessed and compared. In this study, water-storage tanks
      and drums were found to comprise 79% of the containers positive for larval Ae.
      aegypti, which contributed to 93 and 92% of the total production of populations
      of 4th-stage larvae and pupae, respectively. These main breeding sites of Ae.
      aegypti were found at an indoor to outdoor ratio of 2.4:1 and no correlation was
      found between temporal fluctuation of populations of larval Ae. aegypti and
      monthly rainfall. Netted lids that used inexpensive local materials were designed
      to prevent oviposition by Ae. aegypti. During a 6-month trial period, 56% of
      inspected containers had netted lids correctly in place. Of these, 78% had no
      mosquito larvae. Because only 37% of uncovered containers were free of mosquito
      larvae, a significant difference was demonstrated when these inexpensive
      mechanical barriers were used (chi2 = 138.7; P < 0.001). These netted lids and
      the improved methods described to assess the productivity of larval and pupal Ae.
      aegypti in this study are now being used in combination with other strategies to
      assess and control these populations of dengue virus vectors in the main port
      city on the Atlantic Coast of Colombia.

PMID- 11998930
TI  - Association of cyclopoid copepods with the habitat of the malaria vector
      Anopheles aquasalis in the peninsula of Paria, Venezuela.
AB  - The southern region of the Paria Peninsula shows a high malaria incidence. This
      work relates the abundances of cyclopoid species and the malaria vector Anopheles
      aquasalis to certain abiotic parameters and vegetation features. Samples were
      collected over a 4-month period in several habitats, including marsh, irrigation
      channel, lagoon, and mangrove swamp during the wet season and the wet-dry
      transition. Dominant plant species in the marsh were Typha dominguensis and
      Eleocharis mutata. Mesocyclops meridianus also was dominant in the marsh. Highest
      densities of An. aquasalis larvae, as well as lowest pH values and highest
      sulfate concentrations, were found in habitats containing E. mutata. Statistical
      correlation analysis showed that abundances of M. longisetus longisetus and An.
      aquasalis larvae were positively and significantly correlated in the irrigation
      channel, and abundances of M. meridianus and An. aquasalis larvae were negatively
      and significantly correlated in the E. mutata marsh.

PMID- 11998931
TI  - Indoor thermal fogging against vector mosquitoes with two Bacillus thuringiensis
      israelensis formulations, Vectobac ABG 6511 water-dispersible granules and
      Vectobac 12AS liquid.
AB  - Bioefficacy of thermal fogging application of 2 Bacillus thuringiensis
      israelensis formulations, Vectobac ABG 6511 water-dispersible granules (3,000
      international toxic unit [ITU]/mg) and Vectobac 12AS liquid (1,200 ITU/mg), was
      assessed for larvicidal activities against Aedes aegypti, Aedes albopictus,
      Anopheles dirus, and Culex quinquefasciatus. Portable Agrofog AF35 sprayers were
      used to apply the 2 formulations indoors in residential premises on Penang
      Island, Malaysia. Vectobac ABG 6511 showed good larvicidal effect against all 4
      mosquito species at 3 of the higher doses tested (2.91 x 10(9), 1.45 x 10(9), and
      0.71 x 10(9) ITU/ha), with more than 96% mortality at 48 h after spraying. As a
      comparative formulation, Vectobac 12AS also showed good larvicidal activity
      against all 4 mosquito species at 2 of the higher doses tested (2.87 x 10(9) and
      1.46 x 10(9) ITU/ha), with more than 92.5% mortality at 48 h after spraying.
      Larvae of An. dirus were significantly more susceptible to both water-based
      Vectobac formulations when compared to the other 3 mosquito species. Both
      microbial formulations showed better efficacy at higher doses. However, even at
      the lowest dose tested, Vectobac ABG 6511 and Vectobac 12AS (both at 0.36 x 10(9)
      ITU/ha) showed larvicidal properties, with more than 66% mortality at 48 h after
      spraying. Overall, for this bacterial agent, the water-dispersible granule
      formulation has better prospects than the liquid formulation for the control of
      larvae of vector mosquitoes.

PMID- 11998932
TI  - Sterilization of Bacillus thuringiensis israelensis products by gamma radiation.
AB  - This study examines the effect of routine gamma radiation based on cobalt 60 on
      the viability, mosquito larvicidal activity, and density of bacillus spores in
      the soil. Although 1 g of unirradiated powder of Bacillus thuringiensis
      israelensis (Bti) contains on average 6.2 x 10(9) spores, no spores survived
      radiation doses of 20.6 kGy and higher. Radiation at a dose of 20-25 kGy caused a
      20-30% reduction in the effectiveness of Bti powder against mosquito larvae. In
      areas treated with unirradiated Bti material on average twice a year, soil
      contained 700,000 to 44 million spores per gram. In areas treated with irradiated
      Bti products, either no Bti spores or fewer than 100,000 were found per gram of
      soil. A radiation dose of 25 kGy fulfills the requirements of killing all spores
      in a Bti product and maintaining the effectiveness of the product in routine
      treatments. No viable spores remain in water used for household purposes or
      irrigation of garden areas when irradiated Bti fizzy tablets are used in water
      containers. Irradiation of Bti products fulfills the requirements of drinking
      water regulations and thus allows these products to be used widely.

PMID- 11998933
TI  - Survey of Aedes aegypti eggs in and around homes in Tucson, Arizona.
AB  - The abundance and location of eggs of Aedes aegypti were evaluated through
      inspection of 24 Tucson homes during the winter of 1998-99 to assess the
      potential of the mosquitoes to overwinter in this area. Eggs were found either
      indoors or outdoors in 46% of residences surveyed. After immersion in water,
      about 23% of eggs found indoors hatched, and about 5% of eggs found outdoors
      hatched.

PMID- 11998934
TI  - An isolate of Bacillus circulans toxic to mosquito larvae.
AB  - A new strain of Bacillus circulans isolated from a larva of Culex
      quinquefasciatus showed larvicidal activity on 3 mosquitoes of medical
      importance. Compared to Bacillus sphaericus strain 2362, this B. circulans
      isolate proved less toxic to Cx. quinquefasciatus and Anopheles gambiae but was
      107 times more toxic to Aedes aegypti. Moreover, in comparison to other studies,
      B. circulans was at least as pathogenic as B. thuringiensis var. israelensis in
      Ae. aegypti. The tests have showed that the toxicity of the bacterial culture of
      B. circulans resulted from its spores and not from the insecticidal effect of
      chitinases or exotoxins.

PMID- 11998935
TI  - Efficacy of Biomist 30:30 and Aqua Reslin against Anopheles quadrimaculatus in
      Arkansas.
AB  - Aqua Reslin and Biomist 30:30 technical permethrin and piperonyl butoxide were
      applied via ground ultra-low volume at a rate of 237 ml/min and 0.00196 kg active
      ingredient/ha against wild-caught adult Anopheles quadrimaculatus. The 2
      formulations did not differ significantly at 31 m from the spray path (P < or =
      0.05). However, at 61 and 91 m, percent mortality for 30:30 was significantly
      higher than for Aqua Reslin at each time after treatment (P < or = 0.05). Between
      12 and 24 h, about 8% recovery was observed in mosquitoes treated with Aqua
      Reslin at 31 m.

PMID- 11998936
TI  - Comparison of defecatory function after colonic J-pouch anastomosis and straight
      anastomosis for stapled low anterior resection: results of a prospective
      randomized trial.
AB  - PURPOSE: Although defecatory function after low anterior resection for rectal
      cancer is reported to be better following colonic J-pouch than straight
      anastomosis, few prospective randomized trials comparing the two forms of
      anastomosis have been reported. We performed a prospective randomized trial
      comparing straight anastomosis with colonic J-pouch anastomosis both clinically
      and physiologically in patients undergoing stapled low colorectal anastomosis.
      METHODS: A total of 42 consecutive patients were intraoperatively randomized to
      undergo either straight anastomosis or colonic J-pouch anastomosis. Clinical
      defecatory function was evaluated by a questionnaire answered preoperatively,
      then 6 and 12 months postoperatively. Anorectal physiological assessment was also
      carried out before surgery, then 12 months postoperatively. RESULTS: The clinical
      defecatory function assessed 6 months and 12 months after surgery did not differ
      between the two groups. However, while the length of high-pressure zone was
      significantly shortened, and (neo)rectal capacity was significantly reduced
      postoperatively in the straight group, none of these physiological parameters
      were significantly altered in the pouch group. CONCLUSION: Although the aim of
      colonic J-pouch to preserve reservoir function was physiologically achieved, the
      improvement in clinical defecatory function was not significant. Thus, further
      prospective studies are needed to confirm the functional superiority of colonic J
      pouch anastomosis for stapled low colorectal anastomosis after low anterior
      resection.

PMID- 11998937
TI  - Poor neorectal evacuation as a cause of impaired defecatory function after low
      anterior resection: a study using scintigraphic assessment.
AB  - PURPOSE: Patients who have undergone low anterior resection (LAR) of the rectum
      occasionally complain of symptoms related to impaired neorectal evacuation. Using
      scintigraphy, we assessed neorectal evacuation in 22 patients who underwent LAR
      and straight anastomosis, and correlated the results with clinical defecatory
      function, clinical factors, and anorectal manovolumetric parameters. METHODS:
      After the introduction of an artificial stool containing 99mTc-DTPA into the
      neorectum, sequential lateral gamma images were obtained. From the time-activity
      curve of radioactivity in the whole pelvis, the time taken to evacuate half of
      the introduced artificial stool (T(1/2)) and the percentage of artificial stool
      evacuated in 1 min (Evac1) were calculated. RESULTS: The Evac1 was significantly
      lower in the patients who had undergone LAR than in reference normal volunteers.
      A long T(1/2) was significantly associated with worse defecatory function. The
      Evac1 was also significantly lower in patients with a low anastomosis. The rectal
      sensory threshold was significantly greater in patients with a shorter T(1/2).
      The maximum tolerable volume of the neorectum was significantly greater in
      patients with a shorter T(1/2) and a higher Evac1. CONCLUSION: Poor neorectal
      evacuation is associated with impaired defecatory function after LAR. Therefore,
      it is suggested that optimizing both reservoir function and evacuation of the
      neorectum would improve defecatory function after LAR.

PMID- 11998938
TI  - Staple-line ulcer in the ileal reservoir following restorative proctocolectomy.
AB  - PURPOSE: Following restorative proctocolectomy, seven cases with staple line
      ulcer around the pouch anal anastomosis and/or staple line in the ileal pouch
      were experienced. Their clinical, endoscopical characteristics were analyzed.
      METHODS: The patients noted anal bleeding following restorative proctocolectomy
      were examined with colonofiberscopy and histological study was conducted.
      RESULTS: Staple line ulcer was seens in seven cases (2.3%, 7/304). The onset was
      immediate or within 2 months postoperatively in 5 cases. Bleeding occurred in all
      the patients and lower abdominal pain, anal pain, increased bowel movements and
      anal fissure were seen frequently. Ulcers were linear along the staple line and
      there were no cases complicated by simultaneous pouchitis. Most of the patients
      responded to treatments with metronidazol, 5-ASA, and topical or oral steroids,
      although one patient required ligation of bleeding ulcer and two complicated
      perianal excoriation required ileostomy. CONCLUSION: Staple line ulcer should be
      recognized as different complication to pouchitis.

PMID- 11998939
TI  - E-cadherin expression in the primary tumors and metastatic lymph nodes of poorly
      differentiated types of rectal cancer.
AB  - PURPOSE: Dysfunction of E-cadherin, a cell-cell adhesion molecule, correlates
      with the grade of dedifferentiation and/or invasiveness of rectal cancer.
      However, the relationship between E-cadherin expression in the primary tumor and
      the potential for metastasis has never been reported. METHODS: E-cadherin
      expression in 43 primary rectal cancer, including 10 poorly differentiated type,
      and their associated metastatic lymph nodes (LN mets.) were immunohistochemically
      evaluated. RESULTS: Heterogeneous immunostaining, suggestive of damage to the E
      cadherin-mediated cell-cell adhesion system, was seen in 13 of the 28 LN mets
      positive primary lesions, but in 0 of the 15 LN mets negative primaries.
      Furthermore, the incidence of heterogeneous immunostaining differed significantly
      between poorly differentiated and differentiated cancers, being seen in 8 of 10
      cases and 5 of 33 cases, respectively (P = 0.0003 by Fisher's exact test).
      Interestingly, most of the LN mets. foci (25 of 28 cases) showed homogeneous
      staining regardless of the E-cadherin staining pattern of the primary lesion.
      CONCLUSION: Heterogeneous immunostaining of E-cadherin in poorly differentiated
      rectal cancer was associated with lymph node metastasis. Its staining pattern in
      metastatic lymph nodes were, however, generally homogenous.

PMID- 11998940
TI  - A new preoperative grading system for predicting the operative conditions for
      abdominal wall-lifting laparoscopic cholecystectomy.
AB  - PURPOSE: This study was performed to evaluate the operative conditions for an
      abdominal wall-lifting laparoscopic cholecystectomy (ALLC) using a new
      preoperative grading system. METHODS: One hundred forty-five patients who
      underwent a cholecystectomy for cholecystolithiasis from January 1997 to December
      1999 were retrospectively analyzed. Allotting 0-5 points for coexisting
      cholecystitis, past history, previous upper abdominal laparotomy, preoperative
      drainage, location of the stones, and body mass index, the total combined score
      was defined as the predictive score. The cases were graded into four risk groups
      according to the predictive score. The postoperative score, which evaluated the
      actual conditions of ALLC, was defined by allotting 0-8 points to operative
      factors: operation time, blood loss, additional trocars and procedures,
      conversion to open surgery, and postoperative complications. RESULTS: Ten cases
      (6.9%) were converted to open surgery and three cases (2.1%) had minor
      postoperative complications. The conversion rate for each risk group was 0%
      (minimum-risk group), 5.4% (low-risk group), 10.7% (intermediate-risk group), and
      17.9% (high-risk group). The mean operation time was 63.0, 87.5, 89.0, and 120.2
      min. The mean postoperative score was 1.08, 2.81, 3.96, and 6.36, and showed a
      respectively strong correlation with the predictive score (correlation
      coefficient: 0.997). CONCLUSIONS: Our preoperative grading system using the
      predictive score was found to be a reliable and feasible method for predicting
      the actual operative conditions for ALLC.

PMID- 11998941
TI  - The influence of pylorus-preserving partial gastrectomy on carcinogenesis of
      residual gastric mucosa in the rat.
AB  - PURPOSE: The aim of this study is to investigate a pylorus- and vagus-nerve
      preserving partial gastrectomy to discover any correlation to a reduced carcinoma
      occurrence from residual gastric mucosa. METHODS: Wistar rats underwent a distal
      partial gastrectomy (Group D), a pylorus-preserving partial gastrectomy (Group
      P), or a simple laparotomy (as a control) (Group C) while some also underwent an
      additional truncal vagotomy (Groups DV, PV, and CV). Continuous per oral
      administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was given every day
      for 8 weeks before operation. At 3, 6, and 12 months after surgery, the animals
      in each group were administered an intraperitoneal injection of bromodeoxyuridine
      (BrdU). At 1 h after injection, the animal was killed, and the residual stomach
      removed. RESULTS: The histopathological findings showed no intestinal metaplasia
      and no gastric cancer in any group. No abnormality in the gastric mucosa was
      found in either Group C or Group CV. However, anastomotic ulcers, cystic glands,
      and submucosal gland formation were found significantly more in Groups P and in
      PV than in either Groups D or DV (each P < 0.05). Atypical glands were found in
      only one rat in each of Groups D and DV, and gastritis cystica polyposa (GCP) was
      found in only one rat in Group DV. All of these findings occurred in the fundic
      gland mucosa on the oral side of the anastomosis. The BrdU labeling index in this
      fundic gland mucosa was significantly higher in Groups D and DV than that in
      Groups C and CV, at 3, 6, and 12 months postoperatively (P < 0.05). The pH of the
      gastric juice was higher in all those groups that underwent vagotomy, with a
      significant difference only between Groups DV and C (P < 0.05). The concentration
      of bile acids contained in the gastric juice (microM/l) was significantly lower
      in Groups P and PV than that in Groups D or DV (each P < 0.05). CONCLUSION: The
      preservation of the pylorus was considered to be a useful surgical method to
      prevent the retrograde reflux of the duodenal juice into the residual stomach,
      and also reduced the proliferative activity of the residual gastric mucosa on the
      oral side of the anastomosis.

PMID- 11998942
TI  - Analysis of experimental liver metastasis from tumors inoculated in the mouse
      stomach cavity.
AB  - PURPOSE: This study was conducted to develop a patient-like hematogenous
      metastatic model of gastric-cancer in order to gain an understanding of the tumor
      biology and to search for new methods of treatment. METHODS: We established a
      natural and easily reproducible liver metastasis model by orthotopic gastric
      inoculation in Balb/c mice, using the syngeneic tumor, colon 26. RESULTS: This
      model allowed us to evaluate the effect of partial gastric resection with
      excision of tumor nodules on the formation of experimental liver metastases from
      the stomach cavity. Mice given partial gastrectomy showed less metastatic ability
      than control mice. In these experimental groups, liver metastasis was observed in
      the only group of mice that died of local tumor regrowth due to incomplete
      resection of the primary tumor. It is suggested that a period of at least 10 days
      is required for the formation of liver metastases after tumor inoculation into
      the stomach cavity. There was no significant increase in the number of liver
      metastases following splenectomy, or after the administration of anti-asialo GM1
      antibody or silica. CONCLUSION: This experimental model of liver metastases will
      provide a useful means of understanding tumor biology and the regulation of liver
      metastases by host immunocompetent cells, and for assessing new therapeutic
      agents.

PMID- 11998943
TI  - Intra-abdominal ectopic thyroid presenting with hyperthyroidism: report of a
      case.
AB  - Ectopic thyroid tissue has been found in the developmental pathway of the thyroid
      gland and has also been reported in the abdominal cavity. Intra-abdominal thyroid
      tissue was totally resected around the mesentery of the small intestine in a 56
      year-old woman. She had hyperthyroidism preoperatively and had also undergone a
      bilateral subtotal thyroidectomy 10 years earlier. No signs or symptoms of a
      thyroid tumor were present.

PMID- 11998944
TI  - Colonic adenocarcinoma metastatic to the thyroid: report of a case.
AB  - We report herein the case of a 67-year-old man who was admitted to our hospital
      with a 3-month history of hoarseness, a cervical mass, and weak muscles of the
      extremities 6 years after undergoing a right colectomy for carcinoma. Physical
      and imaging examinations disclosed a nodule in the thyroid with swollen cervical
      lymph nodes, multiple pulmonary lesions with pleural effusion, and a cerebral
      mass. Fine-needle aspiration cytology of the thyroid nodule and brush cytology of
      the lung mass revealed adenocarcinoma, which was consistent with a diagnosis of
      metastases from the primary colon adenocarcinoma to the thyroid, brain, and lung.
      The patient eventually died from the malignancy, although he survived for 4
      months after the disclosure of the metastases. The rarity, diagnosis, and
      prognosis of thyroid metastasis from colon carcinoma are discussed.

PMID- 11998945
TI  - A combined thoracoscopic and posterior-spinal approach for "dumbbell"
      neurofibroma minimizes the anatomical destruction of the vertebrae: report of a
      case.
AB  - A dumbbell-shaped neurogenic tumor was resected using a combined approach
      employing a thoracoscopic procedure and limited laminectomy. The part of the
      tumor at the thoracic cavity was first amputated at the orifice of the foramen
      and then removed. Part of the spinal canal and intervertebral foramen was then
      removed by means of limited laminectomy without facetectomy. As a result, surgery
      was performed with a minimum of surgical stress and the patient did not require
      vertebral instrumentation.

PMID- 11998946
TI  - A cyst of benign mediastinal teratoma demonstrating a peculiar development:
      report of a case.
AB  - A 28-year-old woman developed repeated neck swelling and remission over a 4-month
      period. Benign mediastinal teratomas also extended along her cervical region. It
      was not a teratoma which primarily developed in the neck. In this case, rich
      pancreatic tissue was histologically observed. The mechanism of the particular
      extension of the tumor considered to be: (1) an encasement by anatomical
      structures and the right-sided hard wall of the tumor, and (2) pancreatic tissue
      which developed cystic formation.

PMID- 11998947
TI  - Descending or thoracoabdominal aortic aneurysm repair without intercostal vessel
      reconstruction using contrast magnetic resonance angiography: report of two
      cases.
AB  - Two high-risk patients underwent a graft replacement for descending thoracic or
      thoracoabdominal aortic aneurysms without the reconstruction of any intercostal
      and lumbar arteries. The first patient was an 81-year-old woman with asthma and
      renal dysfunction who was diagnosed to have a descending thoracic aortic aneurysm
      extending from the Th8 to Th12 level. Contrast magnetic resonance angiography
      (MRA) demonstrated the Adamkiewicz artery to originate from the left second
      lumbar artery. The second patient was a 59-year-old man with left ventricular
      dysfunction due to aortic and mitral stenoses who was diagnosed to have a
      Crawford type IV thoracoabdominal aortic aneurysm. Contrast MRA showed the
      Adamkiewicz artery to originate from the left ninth intercostal artery. In
      general, the reestablishment of the spinal cord's blood supply, whenever
      possible, is generally considered to be necessary in such patients to prevent
      spinal cord injury. However, the reimplantation of intercostal vessels is the
      most complex aspect of this surgical modality, and therefore, it may cause a
      substantial increase in the cardiopulmonary bypass time. However, at least in
      some cases, such as the two cases presented herein, the use of contrast MRA was
      found to reduce the risk in surgery for descending thoracic or thoracoabdominal
      aortic aneurysms by eliminating the need for any intraoperative management of the
      intercostal and lumbar arteries.

PMID- 11998948
TI  - Ileal perforation in diffuse intestinal Behcet disease: report of a case.
AB  - Intestinal ulcers in Behcet disease tend to cause perforation, and postoperative
      recurrence is common with a high mortality rate. The optimal therapeutic strategy
      has yet to be elucidated, particularly in cases of diffuse intestinal
      involvement. We herein present a case of diffuse intestinal Behcet disease with
      ileal perforation. A 57-year-old Japanese woman was referred to our institution
      with complaints of intractable oral ulcers and abdominal pain. The patient
      underwent an emergency laparotomy for perforated peritonitis in spite of the
      intravenous administration of prednisolone (1.5 mg/kg) under total parenteral
      nutrition. Macroscopically, an inflamed ileum measuring 1.6 m in length was
      resected, including a 1-cm perforated ulceration. Innumerable small and deep
      ulcers were also observed, consisting of nonspecific inflammation. The patient
      has been free from any recurrence of intestinal ulcers while being treated with
      prednisolone, colchicine, and a low-residue diet for 1.5 years.

PMID- 11998949
TI  - Transanal repair of rectourethral fistula after a radical retropubic
      prostatectomy: report of a case.
AB  - Rectourethral fistula occurred in a 64-year-old man after a radical
      prostatectomy. Despite conservative treatment the fistula did not close
      spontaneously. Eleven months after the original prostatectomy, an operation was
      performed. We chose the Latzko technique with slight modifications as follows.
      The patient was placed in the prone jackknife position. The fistula was found at
      a site about 6.0 cm from the anal verge. An elliptical area of rectal mucosa was
      incised about 1.5 cm from the fistulous orifice and subsequently the rectal
      mucosa was denuded. The submucosa was dissected above the fistula about 2.0 cm
      from the edge of the incision. The fistula was then closed with one layer of side
      by-side absorbable 2-0 polyglactin sutures. The dissected rectal mucosal flap was
      brought down over the fistula and sutured in one layer to the distal edge of the
      rectal muscularis propria through the mucosa with 3-0 polyglactin sutures. On
      postoperative day 21 a retrograde urethrogram was made and it showed no leakage
      of urine via the rectum. This procedure is a simple, effective, and minimally
      morbid technique for the repair of rectourethral fistula after a radical
      prostatectomy, although it is only useful for the treatment of low rectourethral
      fistulas.

PMID- 11998950
TI  - Fibrolamellar hepatocellular carcinoma in a Japanese man: report of a case.
AB  - Fibrolamellar hepatocellular carcinoma (FHCC), a rare variant of hepatocellular
      carcinoma, is becoming more prevalent; however, up until 1999, only 18 cases had
      been reported in Japan. We recently diagnosed a case of FHCC in a 46-year-old
      Japanese man who had visited four hospitals before being finally admitted to our
      department. On admission, he was diagnosed as having multiple liver tumors, with
      lymph node metastasis and peritoneal dissemination. Both hepatitis B antigen and
      hepatitis C antibody were negative, and the levels of serum alpha-fetoprotein and
      PIVKA-II were within normal limits. Under a provisional diagnosis of atypical
      hepatocellular carcinoma (HCC), a right hepatic lobectomy with resection of the
      metastatic lymph nodes and peritoneal dissemination was performed. The
      histopathological diagnosis made by our pathologist was atypical HCC. He
      underwent another operation for a recurrence in the left external iliac lymph
      node. It has been 29 months since his first surgery in this hospital and he is
      progressing well, which led us to establish the diagnosis of FHCC. Moreover, his
      serum carbohydrate antigen 125 levels have been well correlated with this
      condition.

PMID- 11998951
TI  - Hepatic splenosis diagnosed as hepatocellular carcinoma: report of a case.
AB  - We report one case of splenosis. A 43-year-old male patient was referred to our
      hospital because of a hepatic mass. The hepatic lesion was incidentally found
      during an annual ultrasonographic follow-up since the patient was a known chronic
      hepatitis B carrier for the previous 10 years. Surgical records revealed a
      history of splenectomy in conjunction with a blunt abdominal trauma, which the
      patient had sustained 20 years prior to this admission. On abdominal computed
      tomography scanning, a 3.5-cm sized focal bulging mass was noted in segment 6 of
      the liver. An inferior phrenic artery angiogram showed a hepatic tumor and the
      patient was treated by chemoembolization for hepatocellular carcinoma. A partial
      resection of the liver with a portion of the diaphragm was done after the
      transcatheter arterial chemoembolization procedure. A pathologic examination
      revealed splenosis within the hepatic parenchyme.

PMID- 11998952
TI  - Acute emphysematous cholecystitis preceded by symptoms of ileus: report of a
      case.
AB  - We herein describe a case of acute emphysematous cholecystitis in which the
      patient presented with symptoms of ileus. The patient was a 72-year-old man with
      no history of diabetes mellitus. He presented with epigastric pain, vomiting, and
      low-grade fever. Plain abdominal radiography showed some intestinal gas and
      niveau, and he was admitted to our hospital with a diagnosis of ileus. The next
      day, the abdominal pain increased and was accompanied by muscular defense. Plain
      radiography and computed tomography of the abdomen were carried out, and an
      emergency laparotomy was performed under a diagnosis of panperitonitis due to a
      perforation of the gallbladder caused by acute emphysematous cholecystitis. The
      patient made favorable progress after the operation and was discharged on
      postoperative day 14. Percutaneous transhepatic gallbladder drainage has been
      increasingly performed for the treatment of acute emphysematous cholecystitis.
      but when a perforation of the gallbladder is suspected, a laparotomy first should
      be considered.

PMID- 11998953
TI  - Bilateral femoral artery aneurysms in a patient with long-standing traumatic
      paraplegia: report of a case.
AB  - The etiology of femoral artery aneurysms is believed to involve the interaction
      of a genetic alteration that predisposes to the loss of arterial wall integrity.
      This is precipitated by local forces such as repeated flexion of the arteries at
      the hip. We describe herein a case of bilateral femoral and right internal iliac
      artery aneurysms that developed in a patient with long-standing paraplegia. This
      could suggest that alterations in the arterial wall caused by stress and kinking
      during hip flexion may not play a principal role in the pathogenesis of
      nonspecific femoral artery aneurysms.

PMID- 11998954
TI  - Successful management of a giant arteriovenous fistula with a combination of
      selective embolization and excision: report of a case.
AB  - We experienced a female patient with a giant arteriovenous fistula in her lumbar
      region, which was successfully managed by a combination of selective embolization
      and a subsequent total excision. Embolization of the giant arteriovenous
      malformation resulted in an immediate decrease in the cardiac output and an
      increase in systemic vascular resistance. Three days after the embolization, a
      total resection of the lesion was achieved under general anesthesia, with a
      minimum amount of blood loss. The large skin defect after a total excision of the
      cutaneous lesion was covered with bilateral latissimus dorsi musculocutaneous
      flaps.

PMID- 11998955
TI  - Sentinel lymph node biopsy as a tool for the staging of ductal carcinoma in situ
      in patients with breast carcinoma.
AB  - PURPOSE: Ductal carcinoma in situ (DCIS) of the breast is defined as stage 0
      disease, but its diagnosis is subject to sampling errors. This study was
      conducted to assess the usefulness of sentinel lymph node biopsy (SLNB) for
      furnishing indirect evidence of the invasion of tumors diagnosed as DCIS.
      METHODS: A total of 201 SLNB procedures performed using a peritumoral tracer,
      being either dye alone or dye plus 99mTc-labeled colloidal albumin, were
      reviewed. The cases of DCIS were selected for analysis, and the results were
      compared with published data. RESULTS: Among ten cases of DCIS studied by SLNB,
      only one had micrometastatic nodal involvement, which was revealed by cytokeratin
      immunostaining, and was limited to the sentinel node. This was a large
      intermediate-grade micropapillary/cribriform-type DCIS. CONCLUSION: These
      findings indicate that while SLNB may be a valuable tool for the staging of
      tumors diagnosed as DCIS, it should not be performed in all cases, but probably
      restricted to large, high-grade, or comedo-type intraductal carcinomas.

PMID- 11998956
TI  - Expression and localization of nm23-H1 in the human placenta.
AB  - The involvement of the nm23 gene, initially documented as a putative metastasis
      suppressor gene, in normal development and differentiation has been supported by
      several investigations. To date, however, localization and expression pattern of
      nm23 in the human placenta has not been determined. In the present study, the
      expression of nm23-H1 was examined by Northern blot and immunohistochemical
      analyses in human placentas from various stages of gestation. In first trimester
      placenta, the villous cytotrophoblast and the extravillous trophoblast exhibited
      strong cytoplasmic staining for nm23-H1. In second trimester and term placentas,
      the few cytotrophoblasts present showed less intense staining than those in first
      trimester placenta. Northern blot analysis demonstrated a progressive decrease in
      nm23-H1 gene expression with advancing gestational age, which is consistent with
      the results obtained by immunohistochemistry. These findings suggest that nm23-H1
      is involved in the differentiation process of the trophoblast, and high levels of
      nm23-H1 expression seem to reflect the proliferating, less differentiated state
      of that reserve.

PMID- 11998957
TI  - Plasma and follicular fluid concentrations of LHRH antagonist cetrorelix
      (Cetrotide) in controlled ovarian stimulation for IVF.
AB  - Cetrorelix was administered in differing daily dosages for controlled ovarian
      stimulation. The dosage levels were 3 mg (9 cycles), 1 mg (19 cycles), 0.5 mg (43
      cycles), 0.25 mg (46 cycles) and 0.1 mg (7 cycles). In the 3 mg, 1 mg and 0.5 mg
      group the respective median plasma concentrations of cetrorelix on the day of
      oocyte pick-up (OPU) were 2.10 ng/ml, 1.42 ng/ml and 0.88 ng/ml and 1.03 ng/ml,
      0.46 ng/ml and 0.49 ng/ml on the day of embryo transfer (ET). In the 0.25 mg and
      0.1 mg groups plasma cetrorelix levels were below the limit of quantification.
      The cetrorelix concentrations in follicular fluid (FF) in the 0.25 mg group were
      detectable in only 14 out of 44 samples, while in the 0.1 mg group no detectable
      concentrations could be obtained. We also examined 80 cycles after single doses
      of 5 mg (7 cycles), 3 mg (42 cycles), and 2 mg (31 cycles) cetrorelix. On the day
      of OPU the respective median plasma concentrations of cetrorelix were 0.57 ng/ml,
      0.62 ng/ml, and 0.56 ng/ml, and 0.61 ng/ml and 0.28 ng/ml on the day of ET in the
      5 mg and 3 mg groups. In the 2 mg group, the plasma concentrations fell to below
      limits of quantification in 8/9 samples on the day of ET. In 26 out of 27 FF
      samples cetrorelix was detectable in the 3 mg single dose group (median level:
      0.69 ng/ml).

PMID- 11998958
TI  - Relationship of follicle number, serum estradiol level, and other factors to
      clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles.
AB  - OBJECTIVE: To determine the characteristics associated with clinical pregnancy
      rate after gonadotropin-induced intrauterine insemination cycles in patients
      without male or tubal factor infertility. MATERIALS AND METHODS: One hundred and
      eighty patients undergoing controlled ovarian hyperstimulation followed by
      intrauterine insemination were included in the study retrospectively. The
      patients' files were retrospectively evaluated with respect to age, number of
      follicles, endometrial thickness and serum hormone levels at baseline and at the
      day of human chorionic gonadotropin (hCG) administration. The patients with male
      or unilateral tubal factor infertility were excluded from the study. RESULTS: The
      serum estradiol level at the day of hCG administration was not correlated with
      the clinical pregnancy rate (r=-0.05, p=0.481). The number of follicles was not
      correlated with the clinical pregnancy rate (r=-0.09, p=0.209). There was no
      significant difference between the clinically pregnants (n=32) and not pregnants
      (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH)
      and estradiol, serum estradiol and LH levels at the day of hCG administration and
      endometrial thickness (p>0.05). Although not statistically significant, a
      pregnancy rate of 14.2% with less than 3 follicles > or = 18 mm is present
      compared to a pregnancy rate of 27.5% with at least 3 follicles > or = 18 mm and
      24% with > or = 4 follicles > or = 18 mm. CONCLUSION: The clinical pregnancy rate
      does not seem to be affected with the number of follicles present at the time of
      intrauterine insemination or the serum estradiol level at the day of hCG
      administration in a controlled ovarian hyperstimulation cycle in non-andrologic
      and non-peritubal factor infertility; however, there is a clear trend towards
      higher pregnancy rates with higher number of follicles.

PMID- 11998959
TI  - Controlled ovarian hyperstimulation and intrauterine insemination for infertility
      associated with endometriosis: a retrospective analysis.
AB  - OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation and
      intrauterine insemination for infertility associated with endometriosis. MATERIAL
      AND METHODS: A retrospective analysis of 260 patients with the only diagnosis of
      endometriosis, or male factor, or tubal factor, or unexplained infertility were
      performed: a total of 56 patients with different stages of endometriosis, a
      control group consisting of 38 patients with male factor infertility, a group of
      26 patients with tubal factor infertility and a group of 140 patients with others
      (unexplained infertility, ovulation disorders, cervical factor). Pregnancy rate,
      hormone levels, endometrial thickness and number of follicles were analyzed.
      RESULTS: Clinical pregnancy rates per patient were similar between endometriosis,
      male factor, tubal factor, and others including unexplained infertility,
      ovulation disorders and cervical factor groups (10.7%, 5.4%, 11.5%, 17.9%,
      respectively; p>0.05). Clinical pregnancy rates per patient were not effected
      between the 2 subgroups of endometriosis as minimal to mild and moderate to
      severe [5.1% (2/39) versus 23.5% (4/17), p=0.19]. CONCLUSION: Endometriosis did
      not affect the clinical pregnancy rate per patient compared to the other
      infertility factors. Endometriosis of various stages have no effect on the
      success of controlled ovarian hyperstimulation combined with intrauterine
      insemination.

PMID- 11998960
TI  - Assessment of the hepatic arterial and portal venous blood flows during pregnancy
      with Doppler ultrasonography.
AB  - PURPOSE: The aim of this study was to evaluate whether the dual hepatic blood
      supply is altered in healthy pregnant women compared with that in nonpregnant
      women. MATERIALS AND METHODS: Flow wave-forms in common hepatic artery and portal
      vein were obtained in 67 healthy pregnant women at 10-40 weeks gestation and 22
      nonpregnant women by using Doppler ultrasonography. RESULTS: In the nonpregnant
      group, the mean (SD) hepatic arterial blood flow, portal venous blood flow, and
      total liver blood flow were 0.57 (0.31) L/min, 1.25 (0.46) L/min, and 1.82 (0.63)
      L/min, respectively. In the healthy pregnant group, the portal venous blood flow
      and total liver blood flow significantly increased after 28 weeks gestation.
      However, the hepatic arterial blood flow remained unchanged during pregnancy.
      There was no relationship between the hepatic arterial blood flow and the portal
      venous blood flow. CONCLUSION: The results demonstrated that the hepatic
      perfusion increased during third trimester compared to nonpregnant level. Because
      the hepatic arterial blood flow remained unchanged during pregnancy, major
      determinant of the increase in the hepatic perfusion was the portal venous
      return. The data suggest that the hepatic arterial and portal venous vascular
      territories have regulatory mechanisms that allow for independent changes during
      pregnancy.

PMID- 11998961
TI  - The effect of intramural and subserous uterine fibroids on implantation and
      clinical pregnancy rates in patients having intracytoplasmic sperm injection.
AB  - Our objective was to assess the effects of intramural and subserous fibroids on
      intracytoplasmic sperm injection (ICSI) in a retrospective case-control study of
      108 women with uterine fibroids and 324 controls. The fibroids were located and
      measured by transvaginal ultrasound performed just before the ICSI cycle and all
      patients had normal endometrial scan. Seventy-three women had intramural and 35
      women had subserous fibroids and the maximum diameter in any patient ranged from
      0.5-10 cm. The number of fibroids in a patient ranged from 1-8. The first cycle
      outcome was compared with an age and body mass index matched 324 ICSI
      patients/cycles. All couples had male factor infertility. The ICSI cycles of
      patients with intramural and subserous fibroids were comparable in terms of the
      days of ovarian stimulation, the total dose of gonadotropin used, estradiol level
      on day of hCG administration, the number of metaphase II oocytes retrieved,
      fertilization and cleavage rates, number and quality of embryos developed and
      transferred. The implantation and clinical pregnancy rates were similar. We
      conclude that the presence of intramural and subserous fibroids does not
      adversely effect clinical pregnancy and implantation rates in patients undergoing
      ICSI.

PMID- 11998962
TI  - Circulating CD34+ cells to predict the adequate harvest of peripheral blood
      progenitor cells in platinum-based chemotherapy.
AB  - OBJECTIVE: The aim of this study was to clarify the appropriate timing for
      peripheral blood progenitor cells (PBPC) harvesting after platinum-based
      mobilization chemotherapy by measurement of the circulating CD34+ cell
      concentrations. PATIENTS AND METHODS: PBPC were collected for autotransplantation
      via a total of 68 leukaphereses in 16 patients with gynecological cancer.
      Circulating CD34+ cell concentrations were measured by CD34-side scatter
      parameter analysis. RESULTS: Data could be fitted into a linear regression line
      described by the equation y = 0.33 + 4.14 x (x) (R2 = 0.256), where y = the
      number of harvested colony-forming unit granulocyte macrophage (CFU-GM
      (x10(5)/kg) and x = the percentage of circulating CD34+ cells and y = 1.747 +
      44.53 x (x) (R2= 0.475), where y = the number of harvested CD34+ cells
      (x10(6)/kg) and x = the percentage of circulating CD34+ cells. Failure to
      mobilize sufficient CFU-GM numbers (>1 x 10(5)/kg) occurred in 29 of 31
      leukaphereses when the percentage of circulating CD34+ cells was less than 0.10%.
      CONCLUSIONS: Harvesting procedure may be avoided when circulating CD34+ cells
      showed less than 0.10% after platinum-based mobilization chemotherapy.

PMID- 11998963
TI  - Effects of sequential combined transdermal and oral hormone replacement therapies
      on serum lipid and lipoproteins in postmenopausal women.
AB  - The aim of this study was to compare the effects of sequential combined
      transdermal and oral postmenopausal hormone replacement therapies on serum lipid
      lipoprotein profiles risk markers for cardiovascular disease. A prospective
      randomize study was designed: Ninety-six healthy nonhysterectomised
      postmenopausal women were randomized to receive either transdermal continuous
      17beta-estradiol, 0.05 mg/d (Estraderm TTS, Novartis, Basel, Switzerland), with
      transdermal sequential norethisterone acetate, 0.25 mg/d (Estragest TTS,
      Novartis, Basel, Switzerland), or oral continuous conjugated equine estrogens,
      0.625 mg/d (Premarin 0.625 mg, Wyeth, Philadelphia, U.S.A.), with oral sequential
      medroxyprogesterone acetate, 10 mg/d (Farlutal 5 mg, Deva, Istanbul, Turkey). 84
      women completed the trial, 42 in oral and 42 in the transdermal group. The serum
      levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides,
      apolipoproteins AI and apolipoproteins B at 6 months after starting treatment
      were compared with baseline values for both therapies. Both oral and transdermal
      therapies significantly reduced serum levels of total cholesterol (208-190 mg/dL
      and 216-199 mg/dL, respectively, p=0.0001) and LDL-cholesterol (128-112 mg/dL and
      140-127 mg/dL, respectively, p=0.001). The serum levels of triglycerides did not
      show any significant change with oral therapy, whereas this lipid fell (128-101
      mg/dL, p=0.0001) significantly with transdermal therapy. We found significant
      decrease in HDL-cholesterol with transdermal therapy while there was no
      significant change with oral therapy. Apolipoproteins AI, the major protein
      component of HDL2 subfraction, was increased by oral therapy and lowered by
      transdermal therapy. As a conclusion, we have found that serum total cholesterol
      and LDL-cholesterol were lowered by both therapies, with no significant
      differences between treatments, whereas there were significant differences
      between treatments according to effects on serum triglycerides and
      apolipoproteins AI.

PMID- 11998964
TI  - Subcapsular hepatic hematoma in an otherwise uncomplicated pregnancy.
AB  - Subcapsular hepatic hematoma is rare in pregnancies not complicated by pre
      eclampsia or the HELLP syndrome. We now report such a case.

PMID- 11998965
TI  - Alopecia related to low dose oral contraceptive.
AB  - We present a patient with diffuse baldness related to low dose oral contraceptive
      (LD-OC). Although LD-OC scarcely induce troublesome side effects if prescribed in
      accordance with Managing Contraceptive Pill Patients Guideline, this trouble
      might become a source of poor compliance to LD-OCs.

PMID- 11998966
TI  - Hemorrhagic infarction of fibroma. MR imaging appearance.
AB  - We experienced a case of hemorrhagic infarction of the ovarian fibroma and that
      indicated the characteristic following appearance: exhibiting a high signal
      intensity area observed at the periphery of mass on T1-weighted MRI (magnetic
      resonance imaging). It was thought that this appearance developed because
      hemorrhagic infarction was caused by subacute ovarian torsion. This is a useful
      finding for suspecting hemorrhagic infarction preoperatively.

PMID- 11998967
TI  - Comparison of short and long ovulation induction protocols used in ART
      applications according to the ovarian response and outcome of pregnancy.
AB  - This retrospective study was designed to determine whether there is any
      difference between short and long protocol ovulation induction with Gonadotropin
      Releasing Hormone agonist (GnRHa) and gonadotropins used in Assisted Reproductive
      Technology (ART) applications according to the number of retrieved oocytes,
      oocyte maturity, fertilization rates, embryo quality and the outcome of
      pregnancies. 240 cycles consisting of in vitro fertilization (IVF) cycles without
      andrologic factor and intracytoplasmic sperm injection (ICSI) cycles were
      evaluated. 112 cycles which were induced by short protocol GnRHa and Follicle
      Stimulating Hormone (FSH) + Human Menopausal Gonadotropin (HMG) combinations and
      128 cycles which were induced by long protocol GnRHa and FSH + HMG combinations
      were compared according to the number of retrieved oocytes, cancellation rate of
      cycles, oocyte maturity, fertilization rates, embryo quality and pregnancy rates.
      The cancellation rate for short protocol cycles were found to be significantly
      higher than those with long protocol. The number of retrieved oocytes, mature
      oocytes and fertilized oocytes were also found significantly lower. The quality
      of embryos did not show any significant difference between these groups. The
      clinical pregnancy rates were evidently found to be high in the long protocol
      cycles. As a conclusion we have found that while the number of retrieved oocytes,
      mature oocytes, fertilized oocytes and clinical pregnancy rates were increasing,
      the cancellation rate of cycles were decreasing significantly in ART cycles
      induced by long protocol.

PMID- 11998968
TI  - Use of sublingual isosorbide dinitrate tablet for manual extraction of a retained
      placenta.
AB  - We present the first report of the use of an isosorbide dinitrate tablet for the
      purpose of uterine relaxation for manual extraction of a retained placenta. The
      tablet administered sublingually proved to be a rapid and effective uterine
      muscle relaxant for manual removal of the placenta without overt adverse effects.

PMID- 11998969
TI  - Twelve cases of placental chorioangioma. Pregnancy outcome and clinical
      significance.
AB  - INTRODUCTION: To determine perinatal complications and pregnancy outcome in 12
      women with chorioangioma of placenta. STUDY DESIGN: During the period between
      January 1986 and December 1997, 12 women with histologic diagnosis of
      chorioangioma of placenta who delivered in our institution were studied. Case
      control study was designed. Sixty women with histologic examination of the
      placenta without chorioangioma were randomly identified as control group matched
      for maternal age and parity. Statistical analyses included t-test, Chi-square
      test and Fisher's exact test when appropriate. RESULTS: Nine cases (75%) were
      diagnosed postnatal. The mean gestational age was significantly lower and preterm
      delivery rate was significantly higher among the chorioangioma group (34 vs. 38.8
      weeks P<0.0001; 66% vs. 10%; P<0.001 respectively). CONCLUSIONS: Chorioangioma of
      the placenta, in a high risk population, although small, is associated with
      significantly higher risk for preterm delivery. This emphasizes the need for
      pathologic examination of all placentas of patients with preterm delivery

PMID- 11998970
TI  - Tubal pregnancy after pomeroy sterilization.
AB  - Tubal sterilization is one of the options chosen by the women who have completed
      their fertility. Although ectopic pregnancy after tubal sterilization is rare,
      all women undergoing this procedure should be informed about the risk of it. An
      ectopic pregnancy in a 36-year-old woman who had undergone tubal sterilization is
      described.

PMID- 11998971
TI  - Vaginal stones with a pinpoint hymenal opening.
AB  - Primary vaginal stones are a rarely reported complication of a congenital vaginal
      septum, an imperforated hymen, vaginal scarring or female circumcision. We report
      a woman who had vaginal stones with a microperforate hymen.

PMID- 11998972
TI  - Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels
      mediates endothelial cell apoptosis.
AB  - Angiotensin II (Ang II) is central to the pathobiology of atherosclerosis. In
      endothelial cells (EC), Ang II induces apoptosis. The MAP kinase ERK1/2 plays a
      key role in regulating cell survival. We therefore investigated the effect of Ang
      II on ERK1/2. Incubation of EC with Ang II led to the dephosphorylation of ERK1/2
      (43% of control). To characterize the phosphatase involved, we investigated the
      effect of Ang II on MAP kinase phosphatase expression. Ang II induced MAP kinase
      phosphatase-3 (MKP-3) mRNA levels to about 2-fold, whereas MKP-1 expression was
      not affected. Transfection with a dominant negative MKP-3 construct (dnMKP-3mt)
      prevented the Ang II-induced ERK1/2 dephosphorylation and apoptosis in EC (p <
      0.001). ERK1/2 inactivation has been shown to result in the dephosphorylation and
      proteasomal degradation of the antiapoptotic protein Bcl-2. Ang II induced the
      degradation of Bcl-2 wild type, whereas the dephosphorylation-resistant Bcl-2
      construct mimicking phosphorylation by ERK1/2 was resistant to Ang II
      stimulation. These results indicate that Ang II-induced apoptosis signaling in
      human EC is mediated via MKP-3-dependent dephosphorylation of ERK1/2, which in
      turn leads to the degradation of Bcl-2.

PMID- 11998973
TI  - Vascular effects of class-III antiarrhythmic drugs: chromanol 293B, but not
      dofetilide blocks the smooth muscle delayed rectifier K+ channel.
AB  - Chromanol 293B and dofetilide are inhibitors of IKs and IKr, i.e., of the slow
      and the rapid component of the delayed rectifier potassium current. The
      specificity of these drugs was tested by investigating their effects on the
      delayed rectifier potassium current in vascular smooth muscle, regulating the
      tone of blood vessels. Using depolarizing step protocols with asymmetrical
      potassium concentrations (135/4.5 mM K+ in pipette/bath), voltage-dependent K+
      currents (IKv) of enzymatically dispersed guinea pig portal vein cells were
      studied in the whole-cell patch-clamp technique. Peak currents were obtained
      within 20 ms (at +50 mV) after activation. During a 10 s test pulse to +60 mV,
      these currents exhibited a relatively fast inactivation with time constants of
      384 ms (Tfast) and 4505 ms (Tslow). Dofetilide was totally ineffective in
      modulating currents; in contrast, after application of chromanol 293B, a steady
      state block of IKv developed within 135 s. The block was concentration-dependent
      with an IC50 of 7.4 microM. Chromanol did not produce any shift in the normalized
      steady-state activation and inactivation curves and the recovery from
      inactivation was not significantly changed. Chromanol 293B similarly inhibited
      delayed rectifier K+ channels whether in their closed or open state, and produced
      an "apparent" acceleration of inactivation, i.e., the drug accelerated the faster
      time constant of inactivation during a 10 s test pulse from 384 ms (control) to
      149 ms (100 microM chromanol). In recent studies, chromanol was described as a
      specific blocker of slowly activating delayed rectifier potassium channels (IKs)
      in cardiomyocytes. The results of this study, however, extend the inhibitory
      spectrum of the drug and demonstrate block of closed and open state delayed
      rectifier K+ currents in portal vein vascular smooth muscle. Such a block could
      possibly contribute to the generation of portal hypertension.

PMID- 11998974
TI  - Electrophysiology of single cardiomyocytes isolated from rabbit pulmonary veins:
      implication in initiation of focal atrial fibrillation.
AB  - Pulmonary veins (PVs) are important foci in initiation of paroxysmal atrial
      fibrillation. However, the mechanisms of the high arrhythmogenic activity of PVs
      are unclear. This study aimed to isolate single cardiomyocytes from PVs and
      evaluate their electrophysiological characteristics and arrhythmogenic potential.
      Cardiomyocytes of rabbit PVs were isolated by retrograde perfusion with digestive
      enzymes from aorta via left ventricle and left atrium. The action potentials and
      ionic currents were investigated in isolated single PV cardiomyocytes using the
      whole-cell clamp technique. Dissociation of PVs yielded single pacemaker
      cardiomyocytes (76%) and non-pacemaker cardiomyocytes with a fast response action
      potential. Both the pacemaker and non-pacemaker cardiomyocytes had similar inward
      Ca2+ currents and transient outward K+ currents. However, the pacemaker
      cardiomyocytes had a smaller inward rectifier K+ current (1.50 +/- 0.22 versus
      4.21 +/- 1.15 pA/pF, P < 0.005) and a larger delayed rectifier K+ current (0.60
      +/- 0.05 versus 0.24 +/- 0.05 pA/pF, P < 0.005) than non-pacemaker
      cardiomyocytes. Acetylcholine induced hyperpolarization and inhibited the
      spontaneous action potential. Isoproterenol (10 nM) accelerated the spontaneous
      activity and induced early or delayed afterdepolarization, which could be
      suppressed by nifedipine. The PV cardiomyocytes with early afterdepolarization
      have a greater prolongation of action potential duration (deltaAPD, +67 +/- 17
      versus -109 +/- 20 ms, P < 0.0001) and a greater increase of inward Ca2+ current
      (0.90 +/- 0.23 versus 0.38 +/- 0.08 pA/pF, P < 0.05) after isoproterenol than
      those with out early afterdepolarization. These findings suggest that PV
      cardiomyocytes have distinct action potentials and ionic current profiles, which
      may be responsible for the high arrhythmogenic activity of the PVs.

PMID- 11998975
TI  - Preconditioning one myocardial region does not neccessarily precondition the
      whole rabbit heart.
AB  - A previous study in dogs indicated that preconditioning (PC) of a specific
      myocardial region not only evoked a local cardioprotective effect but also
      rendered remote myocardium resistant to infarction. In the present study we
      devised a method to test for remote PC in the rabbit which it is not possible to
      ligate two separate coronary branches on the same heart. In situ hearts were
      subjected to PC with two cycles of 5-min regional ischemia/5-min reperfusion.
      Following this in vivo PC protocol, the hearts were removed and perfused on a
      Langendorff apparatus with crystalloid buffer. They then underwent 30 min of
      global ischemia with the entire left ventricle at risk followed by 2 h of
      reperfusion. At the end of the experiment the myocardium previously subjected to
      the in vivo PC protocol (preconditioned region) was identified as the tissue
      without fluorescence after fluorescent particles had been injected into the
      aortic root following reocclusion of the snared branch of the left coronary
      artery. Infarcted myocardium was identified by triphenyltetrazolium chloride
      staining. Tissue salvage was observed only in the preconditioned region where
      13.2 +/- 3.6% of the myocardium infarcted as opposed to 44.6 +/- 1.3% in the
      remaining non-preconditioned left ventricular tissue (p < 0.05, n = 6). In sham
      operated hearts (snare but no PC), infarction was similar in both the snared
      vessel's perfusion territory and the rest of the left ventricular myocardium
      (49.2 +/- 6.5% vs. 43.7 +/- 3.7%, n = 5). Hence PC of one myocardial region does
      not necessarily confer PC protection to all regions of the heart. Because remote
      PC could not be demonstrated in rabbits, this phenomenon may be species or
      protocol-specific, and should not be assumed to occur in man.

PMID- 11998976
TI  - Xanthine oxidase contributes to preconditioning's preservation of left
      ventricular developed pressure in isolated rat heart: developed pressure may not
      be an appropriate end-point for studies of preconditioning.
AB  - Studies of preconditioning frequently use the isolated rat heart model in which
      recovery of post-ischemic function is the end-point. However, function following
      an episode of ischemia/reperfusion represents a composite of both stunning, which
      is related to free radical production and is not attenuated by preconditioning,
      and tissue salvage, the primary effect of preconditioning. Brief
      ischemia/reperfusion is also known to diminish adenosine release during
      subsequent ischemia by a mechanism independent of preconditioning's anti-infarct
      effect. Reduced purine release would diminish generation of free radicals by
      xanthine oxidase in rat heart and thus produce less stunning. In this paradigm
      preserved post-ischemic function in rat heart might look similar to salvage by
      preconditioning, but its mechanism would be quite different and not be relevant
      to the xanthine oxidase-deficient human heart. This hypothesis was tested in
      isolated rat hearts. Control or ischemically preconditioned hearts were subjected
      to 30 min of global ischemia and 60 min of reperfusion, either in the presence or
      absence of 25 micromol/l allopurinol, an inhibitor of xanthine oxidase. In non
      preconditioned hearts allopurinol increased left ventricular developed pressure
      after 60 min of reperfusion from 26 +/- 5 mmHg in control hearts to 47 +/- 7
      mmHg, whereas developed pressure in preconditioned hearts following reperfusion
      was 59 +/- 5 mmHg and was unaffected by allopurinol. Developed pressure in non
      preconditioned hearts treated with allopurinol was midway between that for
      untreated control and preconditioned hearts suggesting that at least 50% of the
      recovery of developed pressure in preconditioned hearts may be related to free
      radical-induced stunning. In xanthine oxidase-deficient rabbit hearts, return of
      function was not different between non-preconditioned and preconditioned hearts.
      Therefore, post-ischemic developed pressure in the rat is significantly affected
      by purine-dependent stunning, and, hence, may be an unreliable marker of tissue
      salvage and also a poor index of what might be cardioprotective in man.

PMID- 11998977
TI  - PKC-delta inhibition does not block preconditioning-induced preservation in
      mitochondrial ATP synthesis and infarct size reduction in rats.
AB  - We have previously demonstrated that cardioprotection induced by the infusion of
      a selective delta1-opioid agonist is mediated by the specific translocation of
      PKC-delta to the mitochondria in in vivo rat hearts and via opening of the
      mitochondrial KATP channel. Ischemic preconditioning (IPC) is also thought to
      involve the translocation of specific isoforms of PKC and KATP channel
      activation. Therefore, we utilized the PKC-delta selective antagonist, rottlerin,
      to assess the effect of inhibition of this isozyme on cardioprotection induced by
      one-cycle of IPC prior to 30 minutes of ischemia and 2 hours of reperfusion.
      Infarct size (IS) was determined by tetrazolium chloride staining and expressed
      as a percent of the area at risk (AAR). Non-preconditioned control animals had an
      IS/AAR of 59.7 +/- 1.6. IPC significantly reduced the extent of myocardial
      infarction (6.3 +/- 1.4). Rottlerin, 0.3 mg/kg, did not alter IS/AAR in control
      animals (55.0 +/- 5.6), and had no significant effect on IS/AAR in preconditioned
      animals (14.4 +/- 3.8). Additionally, we demonstrated, using a luciferase-based
      assay to determine the rate of ATP synthesis and state of mitochondrial
      bioenergetics, that IPC preserves ATP synthesis in the ischemic myocardium and
      that this preservation is attenuated by the isoform non-selective PKC inhibitor,
      chelerythrine, but not by the delta-selective antagonist, rottlerin. These data
      suggest that PKC-delta does not play an important role in IPC and that
      differences in isoform importance are evident during pharmacological versus
      ischemia-induced preconditioning.

PMID- 11998978
TI  - ATP-sensitive potassium channels do not have a main role in mediating late
      preconditioning protection against arrhythmias and stunning in conscious sheep.
AB  - OBJECTIVE: Although late preconditioning protects against stunning following
      several short periods of ischemia-reperfusion, it is not clear if it confers
      protection against stunning and malignant arrhythmias after a sustained
      reversible ischemia, and whether KATP channels are involved as triggers and/or
      end effectors of the protective mechanism. The purpose of this work was thus to
      test these issues in conscious sheep. METHODS: Five groups were considered: CONT
      (control): the animals were submitted to 12 min ischemia followed by 2 h
      reperfusion; SWOP (late preconditioning): on the first day, the animals were
      preconditioned with 6 periods of 5 min ischemia 5 min reperfusion and 24 h later
      they were submitted to 12 min ischemia followed by 2 h reperfusion; GLIB: same as
      CONT with the KATP channel inhibitor glibenclamide (0.4 mg/kg) infused 30 min
      prior to the 12 min ischemia; SWOPG2: same as SWOP with glibenclamide before the
      12 min ischemia; SWOPG1: same as SWOP with glibenclamide prior to the
      preconditioning stimulus. RESULTS: Percent reperfusion recovery of wall
      thickening fraction (% WTh) showed late preconditioning protection against
      stunning throughout reperfusion (SWOP vs CONT, p < 0.01). Arrhythmia severity
      index (ASI) also demonstrated that late preconditioning protects against
      malignant arrhythmias at the onset of reperfusion (CONT: 4.87 +/- 1.62 vs SWOP:
      1.39 +/- 0.93, p < 0.01). Glibenclamide was unable to prevent preconditioning,
      both against stunning and arrhythmia incidence, when administered either before
      the preconditioning stimulus (SWOPG1 vs CONT, p < 0.01) or before the sustained
      ischemia (SWOPG2 vs GLI, p < 0.01). CONCLUSIONS: Results indicate that late
      preconditioning protects against stunning and arrhythmias following a reversible,
      sustained ischemia in conscious sheep and that KATP channel participation is
      negligible as triggers and end effectors of both types of protection.

PMID- 11998979
TI  - Effects of different inotropic interventions on myocardial function in the
      developing rabbit heart.
AB  - The development of the mammalian heart is characterized by substantial changes in
      myocardial performance. We studied the ontogeny of myocardial function with and
      without various inotropic interventions in the developing isolated, antegrade
      perfused rabbit heart (2d, 8d, 14d, 28d, n = 96). Myocardial function was related
      to the protein expression of the sarcolemmal Na(+)-Ca2+ exchanger and to the
      sarcoplasmic Ca(2+)-ATPase. In neonatal hearts an age-dependent increase in
      maximal developed pressure velocity (dP/dtmax) by 45% and peak negative pressure
      velocity (dP/ dtmin) by 75% within days 2 to 8 were observed. In response to
      inotropic intervention with isoproterenol, ouabain, calcium and the Na(+)-channel
      modulator BDF 9148, dP/dtmax and dP/dtmin increased in a concentration dependent
      manner. Significant differences between neonatal, juvenile and adult hearts could
      be demonstrated in a repeated measurement ANOVA model on the concentration
      response curves for BDF 9148 (dP/dtmax and dP/dtmin), ouabain (dP/dtmin) and
      calcium (dP/dtmin), but not for isoproterenol. At the maximum isoproterenol
      concentration of 1 micromol/l, the increase in dP/dtmax and dP/dtmin was
      significantly higher in adult compared to neonatal hearts (t-test, p < 0.01). The
      significant decline of the Na(+)-Ca2+ exchanger protein expression from neonatal
      (1822 +/- 171) to adult hearts (411 +/- 96 S.E.M. [units per 20 microg protein],
      p < 0.01) was related to an increase in myocardial function (dP/dtmax r = 0.63, p
      < 0.01, dP/dtmin r = 0.62, p < 0.01). Contractility, relaxation and the observed
      positive inotropic effects were in general significantly lower in neonatal
      compared to adult hearts. In the individual heart an increase in contractility
      and relaxation was related to a decrease in Na(+)-Ca2+ exchanger expression.

PMID- 11998980
TI  - Heart rate adjustment of magnetic field map rotation in detection of myocardial
      ischemia in exercise magnetocardiography.
AB  - AIMS: We studied the capability of heart rate (HR) adjusted change in
      multichannel magnetocardiogram (MCG) to detect exercise-induced ischemia. METHODS
      AND RESULTS: The MCG and 12-lead ECG were recorded simultaneously during supine
      exercise testing in 17 healthy controls and 24 patients with single vessel
      coronary artery disease (CAD). In the MCG analysis, we plotted the orientation of
      the magnetic field map (MFM) against the HR in each cardiac cycle during
      recovery. A regression line was fitted to the data and the line slope
      (degrees/bpm) was determined. In the ECG, the ST-segment depression vs HR (ST/HR)
      slope was evaluated. The HR adjusted MFM rotation was more extensive in the
      pooled CAD group, and in all subgroups with different stenosed vessel, than in
      the control group at the ST-segment (1.5 +/- 2.1 degrees/bpm vs 0.29 +/- 0.25
      degrees/bpm, p < 0.0005) and at the T-wave apex (0.95 +/- 0.81 degrees/bpm vs
      0.24 +/- 0.25 degrees/bpm, p < 0.0005). Areas under the receiver operating
      characteristic curves of the HR adjusted MFM rotation at the ST-segment (88.5%)
      and the T-wave (86.0%) were higher than the ones without HR adjustment (75.5% and
      68.1%, respectively), and higher than the area of ST/HR slope in the ECG (80.2%).
      CONCLUSION: HR adjusted MFM rotation detects transient ischemia independent of
      the stenosed vessel. HR adjustment improves the performance of the MCG in
      ischemia detection by the analysis of the ST-segment and the T-wave. The MCG was
      superior to the 12-lead ECG.

PMID- 11998981
TI  - Smoothelin is an indicator of reversible phenotype modulation of smooth muscle
      cells in balloon-injured rat carotid arteries.
AB  - Restenosis is the major obstacle interfering with a successful long-term outcome
      of balloon angioplasty. Neointima formation following endothelial injury is the
      result of phenotype modulation and proliferation of smooth muscle cells (SMC). To
      characterize these time-dependent changes, a rat balloon injury model of carotid
      artery restenosis was assessed. We applied monoclonal antibodies recognizing
      desmin, sm-alpha-actin and smoothelin, a novel marker specific for the
      differentiated phenotype of SMC. Neointima formation could be seen from day 7
      after injury onwards. During early phases, the number of smoothelin-positive
      cells in the media was decreased compared with uninjured controls. Smoothelin
      staining was absent in the neointima during formation. Increased levels of
      smoothelin in both media and neointima were observed at days 28 and 56,
      correlating with a decrease in proliferation as assessed by Ki-67 antigen
      staining. No such changes were observed for desmin and sm-alpha-actin. Following
      balloon injury, SMC in both the media and the neointima underwent an early,
      reversible dedifferentiation, followed by proliferation. The novel SMC-specific
      marker protein smoothelin can be used to monitor this SMC (de)differentiation in
      neointima and media. These findings support the pivotal role of SMC phenotype
      modulation in neointima formation and restenosis.

PMID- 11998982
TI  - Low frequency spectral component of heart rate variability and myocardial beta
      adrenoceptor density after acute myocardial infarction.
AB  - OBJECTIVE: The low frequency spectral component (LF; 0.04-0.15 Hz) of heart rate
      variability (HRV) is considered to be an index of sympathetic modulation of sinus
      node activity under physiological conditions, although the relationship is less
      clearly defined in non-physiological conditions. Several cardiovascular diseases
      are characterized by an absent or blunted 24-h pattern of the LF spectral
      component. The aim of the present study was to investigate the relationship
      between chronically increased neural sympathetic efferent drive to the heart,
      quantified in terms of downregulation of myocardial beta-receptors, and the 24-h
      power of the LF spectral component in patients after acute myocardial infarction.
      METHODS: In 24 patients, HRV was analyzed for a 24-h period, one month after an
      uncomplicated Q wave myocardial infarction. The following time domain measures
      and spectral components were calculated: mean RR, SDNN, SDANN, RMSSD, SDNN index,
      pNN50, and very low frequency (VLF), low frequency (LF) and high frequency (HF)
      spectral components. The density of beta-adrenoceptors was measured in vivo by
      positron emission tomography (PET) with 11-CGP-12177. RESULTS: Post-AMI patients
      had normal plasma levels of adrenaline and noradrenaline (respectively 1.48 +/-
      0.18 and 0.28 +/- 0.03 IU/L) but reduced myocardial beta-adrenoceptor density
      (6.86 +/- 0.24 pmol/g). Patients had similar heart rates but lower values of SDNN
      and SDANN compared with control subjects. The absolute and normalized power of
      the spectral components were similar in the two groups, but the usual day-night
      oscillation was blunted in patients. Moreover, the day-night change in the power
      of the LF spectral component was positively related (r = 0.51; p < 0.001) to the
      myocardial beta-adrenoceptor density. CONCLUSIONS: The loss of the day-night
      oscillation of the LF spectral component appears to be a significant marker of
      sustained sympathetic over-activity in post-AMI patients.

PMID- 11998983
TI  - Noninvasive ventilation: a decade of progress.

PMID- 11998984
TI  - A European framework for effective tuberculosis control.

PMID- 11998985
TI  - Mortality in asthmatics over 15 yrs: a dynamic cohort study from 1983-1998.
AB  - The Darlington and Northallerton long-term asthma study observes outcome in
      asthmatics in the light of potential explanatory variables recorded
      prospectively. This paper reports changes in mortality during the study, and
      assesses the relevant risk factors. All asthmatics attending secondary care were
      recruited at 5-yr intervals from 1983 and reviewed 5 yrs later. Demographic and
      functional variables, including a formal estimate of best function were recorded
      prospectively. The dynamic cohort comprised 1,148 asthmatics with 95% follow-up,
      enabling 612 observations in the period 1983/1988, 774 in 1988/93 and 823 in
      1993/98, with 101, 111 and 100 deaths respectively. Principal risk factors for
      mortality were lower social class and best forced vital capacity. Mortality
      relative to 1983 halved by 1993/98 and was reduced against the Darlington
      population, despite an entry forced expiratory volume in one second of 84.7%.
      There was no change in predictive value of risk factors during the study period,
      or with date of entry. This study demonstrates a consistent reduction in
      mortality, which was not entirely a survivor effect, but may be associated with
      changes in management. By 1993/98 mortality approximated to that of the local
      reference population despite a lower than predicted forced expiratory volume in
      one second.

PMID- 11998986
TI  - Incidence of asthma and respiratory symptoms by sex, age and smoking in a
      community study.
AB  - The purpose of this study was to establish incidence rates for a wide range of
      respiratory symptoms and asthma, and relate them to sex, age, and smoking habits.
      A cohort established in 1985 as a random sample from the population of Western
      Norway, aged 15-70 yrs, was followed-up in 1996-1997. Of the initial cohort of
      3,786 subjects, a total of 2,819 replied to mailed questionnaires at both
      baseline and follow-up. The 11-yrs cumulative incidence of asthma was 4.0% in
      males and 3.5% in females. For respiratory symptoms, the cumulative incidences
      for both sexes varied between 2.0% (dyspnoea grade 4) and 25.8% (wheezing), being
      higher in females than males for most symptoms. For calculation of odds ratios
      (ORs) multivariate logistic regression analyses were used. The sex and smoking
      adjusted incidences increased by age for all symptoms except wheezing and attacks
      of dyspnoea. Those starting to smoke within the follow-up had ORs of 1.9-2.2 for
      the cough symptoms compared to never-smokers, after adjusting for sex, age, and
      pack-yrs. To conclude, the 11-yrs incidence of dyspnoea increased with increasing
      pack-yrs, after adjusting for sex, age, and changes in smoking habits. This
      indicated that when analysing other risk factors, adjustment has to be made for
      the risks posed by smoking, sex and age.

PMID- 11998987
TI  - Effect of inhaled heparin on lung function and coagulation in healthy volunteers.
AB  - The aim of the present study was to investigate the safety of increasing doses of
      a well-defined lower respiratory tract (LRT) dose of inhaled heparin with regard
      to pulmonary function and coagulation. Ten volunteers inhaled heparin from
      Sidestream jet nebulizers loaded with 100,000, 200,000, 300,000 or 400,000
      International Units (IU) of heparin. Lung function, antifactor (anti)-Xa,
      activated partial thromboplastin time (APTT), tissue factor pathway inhibitor
      (TFPI), whole blood clotting time, platelets, von Willebrand factor, and C
      reactive protein were determined before and 1, 3, 6, and 24 h after inhalation.
      The highest LRT dose was 32,000 IU heparin. Inhaled heparin did not affect
      pulmonary function. The area under the curve of the anti-Xa activity increased
      with increasing doses of heparin (p=0.005), but remained unchanged for all other
      variables. Peak anti-Xa activity was 0.113 IU x mL(-1) 6 h after inhalation of
      400,000 IU heparin. When compared to baseline values: anti-Xa increased after
      200,000 (p=0.03), 300,000 (p=0.004), and 400,000 IU (p=0.002) heparin; APTT
      increased to a maximum of 1.03 6 h after inhalation of 400,000 IU heparin
      (p=0.05); TFPI increased after 100,000 (p=0.01), 200,000 (p=0.01), 300,000
      (p=0.006) and 400,000 IU (p<0.001). Inhaled heparin delivery of 32,000
      International Units to the lower respiratory tract can safely be inhaled for
      clinical or research purposes.

PMID- 11998988
TI  - Dose-related effects of formoterol on airway responsiveness to adenosine 5'
      monophosphate and histamine.
AB  - Inhaled short-acting beta2-agonists provide greater protection against airway
      responsiveness (AR) to the mast-cell stimulus, adenosine 5'-monophosphate (AMP),
      than to histamine, a direct spasmogen. Both terbutaline and albuterol exhibit
      this mast-cell stabilizing property in a dose-dependent manner. A single dose of
      the long-acting beta2-agonist formoterol has also been reported to have a mast
      cell-stabilizing effect, whereas salmeterol has not. To explore the dose-related
      actions of the long-acting beta2-agonist formoterol on AR, the authors compared
      the acute effects of three doses of formoterol and terbutaline on AR to AMP and
      histamine. In a double-blind, randomized, placebo-controlled, cross-over study,
      25 mild, steroid naive, asthmatic subjects attended on 10 occasions. At each
      visit, subjects inhaled either a single dose of terbutaline (500 microg),
      formoterol (6, 12 or 24 microg) or a matched placebo, administered via
      Turbuhaler, 30 min prior to challenge with both AMP and histamine. Each dose of
      beta2-agonist reduced AR to AMP and histamine. The bronchoprotective effects of
      formoterol (6 microg) and terbutaline (500 microg) were similar in magnitude in
      reducing AR to histamine (mean +/- SD: 3.6 +/- 0.3 and 3.1 +/- 0.3 doubling doses
      (DD)) and AR to AMP (3.5 +/- 0.5 and 3.3 +/- 0.4 DD, respectively). Overall,
      formoterol reduced AR to both spasmogens in a dose-dependent manner. In addition,
      formoterol (12 and 24 microg) provided a significantly greater protective effect
      against AMP than against histamine challenge. It decreased AR by 5.7 +/- 0.6 and
      6.3 +/- 0.7 DD against AMP and 4.3 +/- 0.4 and 4.8 +/- 0.43 DD against histamine,
      respectively. The results of this study indirectly demonstrated an in vivo dose
      dependent mast-cell stabilizing effect of formoterol, in addition to functional
      antagonism on airway smooth muscle. This property of beta2-agonists may have
      clinical benefits in asthma management.

PMID- 11998989
TI  - Skeletal muscle fibre-type shifting and metabolic profile in patients with
      chronic obstructive pulmonary disease.
AB  - The aim of this study was to examine the nature of fibre-type redistribution in
      relation to fibre metabolic profile in the vastus lateralis in chronic
      obstructive pulmonary disease (COPD) and COPD subtypes. Fifteen COPD patients
      (eight with emphysema stratified by high-resolution computed tomography) and 15
      healthy control subjects were studied. A combination of myofibrillar adenosine
      triphosphatase staining and immunohistochemistry was used to identify pure, as
      well as hybrid fibre types. For oxidative capacity, fibres were stained for
      cytochrome c oxidase and succinate dehydrogenase activities, and glycogen
      phosphorylase for glycolytic capacity. The proportion of type-I fibres in COPD
      patients was markedly lower (16% versus 42%), especially in emphysema, and the
      proportion of hybrid fibres was higher (29% versus 16%) compared to controls. The
      proportion of fibres staining positive for oxidative enzymes was lower in COPD
      patients, which correlated with the proportion of type-I fibres. In COPD
      oxidative capacity was lower within IIA fibres. The authors conclude that fibre
      type transitions are involved in the fibre-type redistribution in chronic
      obstructive pulmonary disease. Low oxidative capacity is closely related to the
      proportion of type-I fibres, but an additional reduction of oxidative enzyme
      activity is present within IIA fibres. Fibre-type abnormalities may be aggravated
      in emphysema.

PMID- 11998990
TI  - Bedside methods versus dual energy X-ray absorptiometry for body composition
      measurement in COPD.
AB  - The measurement of body composition is of value in the nutritional assessment of
      patients with chronic obstructive pulmonary disease (COPD). The purpose of the
      present study was to compare two bedside methods for the measurement of body
      composition using dual energy X-ray absorptiometry (DEXA) as a reference method.
      Fat-free mass (FFM) was measured using DEXA, bioelectric impedance analysis (BIA)
      and skinfold anthropometry (SFA) in a cohort of 85 COPD patients accepted for
      pulmonary rehabilitation. Patients whose body mass index was >30 were excluded.
      Relative to DEXA, BIA underestimated FFM, whereas it was overestimated by SFA.
      There was a systematic increase in bias with mean FFM for both DEXA versus BIA
      and DEXA versus SFA, but this was almost eliminated when results were expressed
      as FFM index. Significant sex differences in the bias of BIA and SFA measurements
      of FFM were found. Forty-two (49.4%) patients were identified as nutritionally
      depleted using DEXA. Compared to DEXA, the sensitivity for detecting nutritional
      depletion was 86 and 74% for BIA and SFA, respectively, and the specificity 88
      and 98%, respectively. There are significant intermethod differences in the
      measurement of body composition in chronic obstructive pulmonary disease
      patients. The choice of measurement method will have implications for nutritional
      assessment in chronic obstructive pulmonary disease.

PMID- 11998991
TI  - Characterization of pulmonary vascular remodelling in smokers and patients with
      mild COPD.
AB  - Intimal enlargement of pulmonary arteries is an early change in chronic
      obstructive pulmonary disease (COPD). The cellular and extracellular components
      that are involved in this enlargement are unknown. The present study was designed
      to characterize the structural changes occurring in pulmonary muscular arteries
      in the initial disease stages. Lung specimens from patients with moderate COPD
      (n=8; forced expiratory volume in one second (FEV1), 66 +/- 10% predicted) and
      smokers without airflow obstruction (n=7; FEV1, 86 +/- 6% pred), were
      investigated by histochemistry to characterize extracellular matrix proteins and
      by immunohistochemistry to identify intrinsic cells of the vascular wall. In both
      COPD patients and smokers, the majority of cells present in the enlarged intimas
      were stained by specific smooth muscle cell (SMC) markers. No staining with
      endothelial or fibroblast markers was shown. A proportion of SMCs did not stain
      with desmin, suggesting cellular heterogeneity in this population. Elastin was
      the most abundant extracellular matrix protein and collagen was seen in a lower
      proportion. The amount of collagen was related to the intimal thickness
      (p<0.001). The findings demonstrated smooth muscle cell proliferation, as well as
      elastin and collagen deposition, in the thickened intimas of pulmonary arteries
      in moderate chronic obstructive pulmonary disease patients and smokers,
      suggesting that these abnormalities may originate at an early stage in cigarette
      smoke-induced respiratory disease.

PMID- 11998992
TI  - Pharmacodynamic steady state of tiotropium in patients with chronic obstructive
      pulmonary disease.
AB  - Tiotropium (Spiriva) is a new once-daily inhaled anticholinergic that has its
      effect through prolonged muscarinic (M)3 receptor antagonism. It has a clinically
      documented, long duration of action with once-daily dosing in chronic obstructive
      pulmonary disease (COPD). A single-centre, double-blind, ipratropium-controlled
      study was conducted in order to characterize the onset of pharmacodynamic steady
      state of tiotropium in patients with COPD. Thirty-one patients (25 male, six
      female) with a mean age of 62 yrs and a mean forced expiratory volume in one
      second (FEV1) of 1.13 L (38% of predicted) were randomly assigned to receive
      either tiotropium 18 microg once-daily from a dry-powder inhaler (HandiHaler, 20
      patients), or ipratropium 40 microg four-times daily from a pressurized metered
      dose inhaler (11 patients) for a period of 1 week. FEV1 and forced vital capacity
      (FVC) were measured 1 h prior to, and just before inhalation (mean value of the
      two measurements on test-day 1 was the baseline value, while on all other test
      days it was the trough value), and 0.5, 1, 2, 3, 4, 5, and 6 h after inhalation
      of the morning dose of the study drug (one capsule and two puffs) on days 1, 2,
      3, and 8. Trough FEV1 following 8 days of tiotropium was 0.19 L (18%) above
      baseline. Approximately 90% of this increase was achieved within 24 h of the
      first dose (0.17 L, 16%). Trough FVC increased 0.67 L (27%) on test-day 8.
      Approximately 70% of the improvement was observed after two tiotropium doses
      (0.47 L, 19%). Achievement of FVC steady state was delayed compared to FEV1.
      Ipratropium performed typically with an onset of action within 30 min, a peak
      response between 1-2 h postdosing and a duration of action of approximately 4 h.
      It was concluded that forced expiratory volume in one second steady state with
      tiotropium is reached within 48 h, while continued improvements in forced vital
      capacity can be expected over or beyond the first week of therapy. The continued
      increases in forced vital capacity beyond 48 h suggests that maintenance
      bronchodilator therapy is required to achieve maximal changes in hyperinflation.

PMID- 11998993
TI  - Is waking electroencephalographic activity a predictor of daytime sleepiness in
      sleep-related breathing disorders?
AB  - No data are available in the literature assessing the potential use of waking
      electroencephalographic (EEG) activity in the detection of excessive daytime
      sleepiness (EDS) in patients with sleep-related breathing disorders (SRBD). The
      aim of this study was to evaluate whether waking EEG spectral power reflects the
      level of EDS in SRBD patients. The study was performed in 48 patients in whom
      quantitative EEG analysis, including the alpha attenuation coefficient (AAC), was
      performed. Sleepiness was assessed by the Epworth Sleepiness Scale, the Stanford
      Sleepiness Scale, the Visual Analogue Scale and the maintenance of wakefulness
      test. Although AAC and EEG spectral power tended to vary throughout the day, none
      of these variations correlated with EDS measures. Waking EEG measures were not
      different between snorers and apnoeic patients. Compared to nonsleepy patients,
      sleepy patients had greater theta and slow alpha powers, but the differences did
      not reach statistical significance. The EEG slowing was independent of
      hypoxaemia, severity of SRBD, or degree of sleep disruption. The authors conclude
      that waking electroencephalographic measures are not sensitive enough to predict
      variation in alertness or to differentiate sleepy from nonsleepy sleep-related
      breathing disorders patients. The degree of electroencephalographic slowing was
      related neither to sleep disruption nor to severity of sleep-related breathing
      disorders.

PMID- 11998994
TI  - Determinants of Fi,O2 with oxygen supplementation during noninvasive two-level
      positive pressure ventilation.
AB  - To maintain arterial oxygen saturation (Sa,O2) above 90% in patients with acute
      respiratory failure, oxygen (O2) is often added to the circuit of two-level
      noninvasive positive pressure ventilation (NPPV). However, the final inspiratory
      oxygen fraction (Fi,O2) is not known. To clarify this issue, the effect of
      different inspiratory positive airway pressures (IPAP) of the oxygen tubing
      connection site and the flow rate of O2, on Fi,O2 was assessed. The effects of
      the tidal volume (VT) and the respiratory rate on the Fi,O2 were then clarified
      in a model study. The Fi,O2 varied depending on the point where O2 was added to
      the circuit. When all other variables were constant, the connection closest to
      the exhaust port (ventilator side) gave the highest Fi,O2. Increases in IPAP led
      to decreases in Fi,O2. Finally, Fi,O2 increased with O2 flow, although it was
      difficult to obtain an Fi,O2 >0.30 unless very high O2 flows were used.
      Paradoxically, NPPV with low IPAP values and without O2 supplementation led to a
      Fi,O2 <0.21 at the circuit-patient interface. VT and respiratory rate did not
      appear to influence Fi,O2. To conclude, when using noninvasive positive pressure
      ventilation with two-level respirators, oxygen should be added close to the
      exhaust port (ventilator side) of the circuit. If inspiratory airway pressure
      levels are >12 cmH2O, oxygen flows should be at least 4 L x min(-1).

PMID- 11998995
TI  - Nocturnal periodic breathing in primary pulmonary hypertension.
AB  - Cheyne-Stokes respiration is frequently observed in congestive heart failure.
      Among other factors, prolongation of circulation time, hypocapnia and hypoxia are
      thought to underlie this sleep-related breathing disorder. Primary pulmonary
      hypertension (PPH) is also characterized by reduced cardiac output and blood gas
      alterations. Therefore, the aim of the present study was to determine whether a
      nocturnal periodic breathing (PB) occurs in PPH. A total of 20 consecutive
      patients with PPH who had been admitted for pharmacological investigation of
      pulmonary vasoreactivity were investigated by lung function testing, right heart
      catheterization and full-night attended polysomnography. PB was detected in six
      patients (30%) (mean +/- SEM: apnoea/hypopnoea index 37 +/- 5 h(-1); arterial
      oxygen saturation was <90% during 56 +/- 6.5% of total sleep time). The patients
      with PB had more severe haemodynamic impairment than those without. They also had
      a more marked reduction in the pulmonary diffusion capacity and greater arterial
      hypoxia. PB was markedly improved or even eradicated by nasal oxygen during the
      night. Periodic breathing occurs in patients with advanced primary pulmonary
      hypertension and can be reversed by nocturnal nasal oxygen. The clinical and
      prognostic significance of periodic breathing in primary pulmonary hypertension
      needs to be determined by further studies.

PMID- 11998996
TI  - Lung cGMP release subsequent to NO inhalation in pulmonary hypertension:
      responders versus nonresponders.
AB  - Inhalation of nitric oxide (NO) is widely employed for the assessment of
      pulmonary vasoresponsiveness in pulmonary hypertension (PH). However, the reasons
      for the huge differences in vascular reactivity to NO between patients are
      unknown, and the role of NO-induced cyclic guanosine monophosphate (cGMP) is
      unclear. Twenty patients with severe precapillary PH were investigated. Thirty
      six Swan-Ganz catheter investigations were performed and the study subjects were
      tested for responses to NO inhalation. This included an assessment of pulmonary
      and systemic arterial plasma cGMP and atrial natriuretic peptide (ANP) levels. A
      significant NO response (pulmonary vascular resistance (PVR) decrease >20%) was
      noted in nine of 20 patients (45%) during the first catheterization. A highly
      significant correlation between baseline plasma cGMP and ANP levels with PVR was
      observed (r=0.62 and r=0.66, respectively; p<0.0001). In response to NO, systemic
      and mixed venous cGMP levels increased from 13.9 +/- 1.28 nM and 12.75 +/- 0.99
      nM to 79.23 +/- 4.99 nM and 55.25 +/- 4.41 nM (p<0.001), respectively,
      accompanied by the appearance of a marked transpulmonary cGMP gradient. Although
      in the responder group ANP levels were significantly reduced after NO inhalation,
      no significant correlation was observed to the extent of PVR reduction. The
      magnitude of the NO-elicited cGMP response did not discriminate between
      haemodynamic responders and nonresponders. This study concludes that plasma
      cyclic guanosine monophosphate levels are significantly correlated with the
      severity of disease in pulmonary arterial hypertension. Nitric oxide inhalation
      provokes a prompt increase in cyclic guanosine monophosphate secretion, but the
      magnitude of this release is not linked with a decrease in pulmonary vascular
      resistance.

PMID- 11998997
TI  - Human alveolar epithelial cells induce nitric oxide synthase-2 expression in
      alveolar macrophages.
AB  - It was hypothesized that cell-to-cell interaction between human alveolar
      macrophages (AM) and alveolar epithelium, might be an important factor leading to
      nitric oxide synthase-2 (NOS2) messenger ribonucleic acid (mRNA) and protein
      expression by constituent cells of the alveolar wall and/or AM. NOS2 mRNA and the
      protein expression patterns of human AM and alveolar epithelial cells type II
      (AEC-II) isolated from normal parts of lung resections of patients with pulmonary
      malignancies were determined. In addition, NOS2 mRNA expression in human AM co
      cultured with autologous AEC-II in the presence of pro-inflammatory cytokines
      interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, interferon (IFN)
      gamma or lipopolysaccharide (LPS) was investigated. The effect of human
      surfactant protein-A (SP-A) on IFN-gamma-mediated NOS2 mRNA expression in human
      AM was also studied. Neither NOS2 mRNA nor protein could be detected in freshly
      isolated, unstimulated or cytokine-stimulated AEC-II. In contrast, freshly
      isolated AM from bronchoalveolar lavage or lung tissue samples expressed
      immunoreactivity for NOS2 protein, but no NOS2 mRNA could be detected by reverse
      transcriptase polymerase chain reaction. All stimuli tested failed to induce NOS2
      mRNA expression in human AM in vitro. Only AM-AEC-II co-culture in the presence
      of IFN-gamma led to NOS2 mRNA and protein expression. In situ hybridization of
      NOS2 mRNA on lung tissue explants and immunohistochemical staining of cytospin
      preparations of AM-AEC-II co-cultures demonstrated that NOS2 is expressed in AM
      but not in AEC-II. This co-culture effect could not be reproduced by substitution
      of AEC-II with SP-A. These data give evidence of a regulatory network controlling
      human nitric oxide synthase-2 expression in the lower respiratory tract.

PMID- 11998998
TI  - Prostaglandin D2 inhibits fibroblast migration.
AB  - Fibroblasts play an important role in the repair and remodelling processes
      following injury. Prostaglandin D2 (PGD2) is a potent mediator in inflammatory
      processes. In this study, the effect of the PGD2 on human foetal lung fibroblasts
      (HFL-1) chemotaxis induced by human plasma fibronectin (HFn) was investigated
      using the blindwell chamber technique. PGD2 inhibited HFL-1 chemotaxis to HFn (20
      microg x mL(-1)) by 20.8 +/- 3.8% (p<0.05). Checkerboard analysis of HFn-directed
      migration confirmed that PGD2 inhibited both chemotaxis and chemokinesis. The
      effect of PGD2 was concentration-dependent and the inhibitory effect diminished
      with time. The PGD2 receptor (DP) agonist BW245C (500 nM) had a similar effect,
      inhibiting chemotaxis to 39.4 +/- 6.3%. The inhibitory effects of both PGD2 and
      BW245C on HFL-1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2
      microM). The inhibitory effect of PGD2 on fibroblast chemotaxis was also blocked
      by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)
      inhibitor, KT5720, suggesting a DP receptor-initiated, cAMP-dependent effect
      mediated by PKA. Prostaglandin D2 appears to inhibit fibroblast chemotaxis,
      perhaps by modulating the rate of fibroblast migration. Such an effect may
      contribute to regulation of the wound healing response following injury in asthma
      patients.

PMID- 11998999
TI  - Traffic-related air pollution and respiratory health during the first 2 yrs of
      life.
AB  - As part of an international collaborative study on the impact of Traffic-Related
      Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with
      long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5
      microm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The
      German part of the TRAPCA study used data from subpopulations of two ongoing
      birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and
      Influences of Lifestyle Related Factors on the Human Immune System and
      Development of Allergies in Children (LISA)) based in the city of Munich.
      Geographic information systems (GIS)-based exposure modelling was used to
      estimate traffic-related air pollutants at the birth addresses of 1,756 infants.
      Logistic regression was used to analyse possible health effects and potential
      confounding factors were adjusted for. The ranges in estimated exposures to
      PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 microg m(-3), 1.38-4.39 x 10(-5)
      m(-1), and 19.5-66.9 microg x m3, respectively. Significant associations between
      these pollutants and cough without infection (odds ratio (OR) (95% confidence
      interval (CI)): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75),
      respectively) and dry cough at night (OR (95% CI): 1.31 (1.07-1.60), 1.27 (1.04
      1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found.
      In the second year of life, these effects were attenuated. There was some
      indication of an association between traffic-related air pollution and symptoms
      of cough. Due to the very young age of the infants, it was too early to draw
      definitive conclusions from this for the development of asthma.

PMID- 11999000
TI  - The effect of air pollution on inner-city children with asthma.
AB  - The effect of daily ambient air pollution was examined within a cohort of 846
      asthmatic children residing in eight urban areas of the USA, using data from the
      National Cooperative Inner-City Asthma Study. Daily air pollution concentrations
      were extracted from the Aerometric Information Retrieval System database from the
      Environment Protection Agency in the USA. Mixed linear models and generalized
      estimating equation models were used to evaluate the effects of several air
      pollutants (ozone, sulphur dioxide (SO2), nitrogen dioxide (NO2) and particles
      with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on peak expiratory
      flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4-9
      yrs). None of the pollutants were associated with evening PEFR or symptom
      reports. Only ozone was associated with declines in morning % PEFR (0.59% decline
      (95% confidence interval (CI) 0.13-1.05%) per interquartile range (IQR) increase
      in 5-day average ozone). In single pollutant models, each pollutant was
      associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16
      (95% CI 1.02-1.30) per IQR increase in 4-day average ozone, OR=1.32 (95% CI 1.03
      1.70) per IQR increase in 2-day average SO2, OR=1.48 (95% CI 1.02-2.16) per IQR
      increase in 6-day average NO2 and OR=1.26 (95% CI 1.0-1.59) per IQR increase in 2
      day average PM10. This longitudinal analysis supports previous time-series
      findings that at levels below current USA air-quality standards, summer-air
      pollution is significantly related to symptoms and decreased pulmonary function
      among children with asthma.

PMID- 11999001
TI  - Induced sputum: time from expectoration to processing.
AB  - One of the limitations in the use of induced sputum to measure indices of airway
      inflammation is the perceived need to process the sample within 2 h. Therefore,
      the authors investigated whether the processing of induced sputum could be
      delayed. Induced sputum samples obtained from asthmatic subjects (n=30) were
      examined. Each sample was stored at 4 degrees C. A portion was selected and
      processed within 2 h and the remaining expectorate (sputum plus saliva) was
      refrigerated. Later an equal amount was selected and processed at either 9 (n=15)
      or 18 (n=15) h. The sputum was examined for cell counts and viability, fluid
      phase eosinophil cationic protein (ECP), interleukin-8 (IL-8) and fibrinogen.
      Repeatability of measurements was assessed by the interclass correlation
      coefficient (ICC). Measurements obtained at 9 h did not differ from those made at
      2 h and the repeatability was excellent (ICC 0.88-0.99). However, by 18 h the
      median cell viability was reduced from 65.0% to 43.0% and the ICC was generally
      lower: 0.10 for total cell count, 0.24 for viability, 0.60 for neutrophils, 0.90
      for eosinophils, 0.56 for macrophages, 0.76 for ECP, 0.82 for IL-8 and 0.84 for
      fibrinogen. The results indicate that when induced sputum from subjects with
      asthma is kept at 4 degrees C, examination of cell counts can be delayed for < or
      = 9 h and for the fluid-phase indices measured for < or = 18 h. Further
      investigation of this issue is required for spontaneous sputum, other airway
      diseases and other inflammatory markers.

PMID- 11999002
TI  - The role of thrombophilic risk factors in the severity of pulmonary
      thromboembolism.
AB  - High plasma factor-VIIIc concentration, presence of factor-V 1691 G-A (FVL) and
      prothrombin20210A (PT20210A) mutations were shown to be significant risk factors
      for venous thromboembolism (VTE) and recurrent VTE. The objective of this study
      was to investigate the role of these thrombotic risk factors in the severity of
      pulmonary thromboembolism (PTE). The plasma concentrations of factor VIIIc,
      presence of FVL and PT20210A mutations were studied in 32 patients with PTE.
      Eleven of the patients had documented recurrent VTE. Lung perfusion scans were
      scored according to the percentage of vascular obstruction. Patients who had a
      pulmonary vascular obstruction score (PVOs) >50% were compared to those with PVOs
      <50%. There was no significant difference between the patients with PVOs >50% and
      those with PVOs <50%, with regard to the presence of FVL and PT20210A mutation.
      However, patients with PVOs >50% had a significantly higher factor-VIIIc
      concentration than those with PVOs <50% (factor-VIIIc levels were 253.3 +/- 29.1
      International Units (IU) x dL(-1) and 138.5 +/- 16.2 IU x dL(-1), respectively;
      p<0.005). Factor-VIIIc concentrations were significantly correlated with PVOs
      (r=0.52, p<0.005). Patients with recurrent VTE had significantly higher factor
      VIIIc concentrations than those in which it occurred for the first time (factor
      VIIIc concentrations were 232.6 +/- 30.9 IU x dL(-1) and 158.3 +/- 20.6 IU x dL(
      1), respectively; p<0.05). The authors conclude that in addition to being a risk
      factor for venous thromboembolism, high factor-VIIIc concentration is an
      important factor in the severity of pulmonary thromboembolism.

PMID- 11999003
TI  - Noninvasive ventilation for acute respiratory failure.
AB  - Noninvasive ventilation (NIV) has emerged as a significant advance in the
      management of respiratory failure. There is now a wide body of prospective
      randomized-controlled trial data to support its use, particularly in the
      management of patients with acute or respiratory failure due to exacerbations of
      chronic obstructive pulmonary disease (COPD). Its successful application results
      in a more rapid resolution of the physiological derangements, reduces the need
      for intubation and, in larger studies, improves survival. A reduction in the
      number of infectious complications is a particular advantage. In patients with
      acute exacerbations of COPD there is evidence of benefit when NIV is introduced
      earlier in the course of the illness than would be the case for invasive
      ventilation and it should now be considered even with mild acidosis (pH<7.35) and
      tachypnoea (respiratory rate >23 breaths x min(-1)) after initial medical
      therapy. There is less clinical-trial data in patients with hypoxaemic
      respiratory failure, but again as with COPD those with less severe physiological
      disturbance are more likely to benefit. By contrast noninvasive continuous
      positive airways pressure, while being widely used has not been shown to reduce
      the need for intubation or to improve survival in patients with hypoxaemic
      respiratory failure, with the exception of acute cardiogenic pulmonary oedema.
      Noninvasive ventilation has been a real advance in the treatment of the
      critically ill. Most of the studies published to date, have excluded patients
      needing immediate intubation and it should be viewed as a complimentary technique
      rather than an alternative to invasive ventilation. It is best viewed as a means
      of preventing the need for endotracheal intubation and as a result should be
      introduced earlier than would be the case for invasive ventilation.

PMID- 11999004
TI  - Diagnostic imaging of lung cancer.
AB  - Carcinoma of the bronchus is the most common malignancy in the Western world. It
      is also the leading cause of cancer-related death accounting for 32% of all
      cancer deaths in males and 25% in females. In the USA it causes more deaths than
      cancers of the colon, breast and prostate combined. Disappointingly, in a recent
      UK survey of improvements in cancer survival, carcinoma of the bronchus showed
      the smallest percentage reduction in the number of deaths avoided between 1981
      1990 (0.2%). This compares badly with breast (11% reduction) and melanoma (32%).
      The overall 5-yr survival for lung cancer diagnosed between 1986-1990 was only
      5.3% (against 66% for breast and 76% for melanoma). It is on this background that
      the radiologist remains actively employed in the detection, diagnosis, staging
      and review of this common malignancy.

PMID- 11999005
TI  - Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic
      patients.
AB  - Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in
      neutropenic patients. Microbiological and serological tests are of limited value.
      The diagnosis should be considered in neutropenic patients with fever not
      responding to antibiotics, and typical findings on thoracic computed tomography
      scan. Whenever possible, diagnosis should be confirmed by tissue examination.
      Newer techniques, such as polymerase chain reaction may change the current
      diagnostic approach. Therapeutic strategies consist of prophylaxis in risk groups
      and the early application of antifungal agents in suspected or probable disease.
      Amphotericin B as desoxycholate or lipid formulation is the current standard
      medication in invasive infection, although it has major side effects. Its role is
      challenged by the new azole derivates, such as itraconazole and voriconazole, and
      the new echinocandins. Additional therapies with cytokines, such as granulocyte
      macrophage colony stimulating factor and interferon-gamma, and with granulocyte
      transfusions are under evaluation. In selected cases lung resection is of proven
      diagnostic and therapeutic value. This paper analyses the current understanding
      of the pathogenesis and epidemiology of invasive aspergillosis and reviews the
      actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis
      in neutropenic patients.

PMID- 11999006
TI  - Sulphasalazine and lung toxicity.
AB  - Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood
      dyscrasias are rare side-effects. Numerous case reports have been published
      implicating sulphasalazine in pulmonary toxicity. The authors searched the
      literature for cases of sulphasalazine induced lung toxicity and the 50 cases
      identified are discussed here. All published case reports/letters referring to
      sulphasalazine and lung toxicity were studied. The search terms "sulphasalazine"
      and "sulfasalazine" were combined with the terms "lung", "pulmonary disease",
      "pneumonitis" and "pleuritis" using Medline and PubMed databases. Typical
      presentation of sulphasalazine-induced lung disease was with new onset dyspnoea
      and infiltrates on chest radiography. Common symptoms were cough and fever.
      Crepitations on auscultation and peripheral eosinophilia were noted in half of
      the cases. Sputum production, allergy history, rash, chest pain and weight loss
      were inconsistent findings. Pulmonary pathology was variable, the commonest being
      eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation
      with or without fibrosis. Fatal reports were infrequent. Most patients were
      managed by drug withdrawal with 40% prescribed corticosteroids. In conclusion,
      sulphasalazine lung disease should be distinguished from interstitial lung
      disease due to underlying primary disease. Despite the increase in sulphasalazine
      prescribing, pulmonary toxicity remains rare. The majority of patients with
      suspected sulphasalazine-induced lung disease improved within weeks of drug
      withdrawal and the need for corticosteroids is debatable.

PMID- 11999007
TI  - European framework for tuberculosis control and elimination in countries with a
      low incidence. Recommendations of the World Health Organization (WHO),
      International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal
      Netherlands Tuberculosis Association (KNCV) Working Group.
AB  - As countries approach the elimination phase of tuberculosis, specific problems
      and challenges emerge, due to the steadily declining incidence in the native
      population, the gradually increasing importance of the importation of latent
      tuberculosis infection and tuberculosis from other countries and the emergence of
      groups at particularly high risk of tuberculosis. Therefore, a Working Group of
      the World Health Organization (WHO), the International Union Against Tuberculosis
      and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association
      (KNCV) have developed a new framework for low incidence countries based on
      concepts and definitions consistent with those of previous recommendations from
      WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of
      interventions is available and feasible, including: 1) a general approach to
      tuberculosis which ensures rapid detection and treatment of all the cases and
      prevention of unnecessary deaths; 2) an overall control strategy aimed at
      reducing the incidence of tuberculosis infection (risk-group management and
      prevention of transmission of infection in institutional settings) and 3) a
      tuberculosis elimination strategy aimed at reducing the prevalence of
      tuberculosis infection (outbreak management and provision of preventive therapy
      for specified groups and individuals). Government and private sector commitment
      towards elimination, effective case detection among symptomatic individuals
      together with active case finding in special groups, standard treatment of
      disease and infection, access to tuberculosis diagnostic and treatment services,
      prevention (e.g. through screening and bacille Calmette-Gueria immunization in
      specified groups), surveillance and treatment outcome monitoring are
      prerequisites to implementing the policy package recommended in this new
      framework document.

PMID- 11999008
TI  - Inhibition of granulocyte activation by surfactant in a 2-yr-old female with
      meningococcus-induced ARDS.
AB  - Activated polymorphonuclear neutrophils (PMNs) play a crucial role in acute
      respiratory distress syndrome (ARDS) via extracellular release of reactive cell
      products such as elastase. Surfactant has proved valuable in restoring lung
      function in ARDS. The significance of its immunomodulatory properties with
      respect to this effect has not yet been clarified. The aim of the present study
      was to determine the anti-inflammatory effects of surfactant administration in an
      infant with ARDS. During the acute phase of ARDS in a 2-yr-old female, levels of
      PMN-derived elastase complexed with alpha1-protease inhibitor (E-alpha1PI) were
      measured in both arterial and central venous blood samples obtained
      simultaneously. The results were correlated with oxygen demand and plasma
      concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
      6) after endotracheal administration of surfactant (Alveofact 60 mg x kg x body
      weight(-1)). In the present case, for the first time, a higher E-alpha1PI
      concentration was detected in arterial blood (4.51 mg x L(-1)) than in central
      venous blood (2.28 mg x L(-1)). After administration of surfactant, these
      concentrations and the arteriovenous difference decreased, indicating that during
      ARDS, most PMN degranulation takes place in the pulmonary vascular bed and is
      inhibited by surfactant administration. Simultaneously, TNF-alpha and IL-6 plasma
      concentrations decreased within hours and lung function was restored. This local
      inhibition of polymorphonuclear neutrophil activation by exogenous surfactant may
      play a key role in the early improvement in lung function after surfactant
      administration.

PMID- 11999009
TI  - Dyspnoea and cyanosis in a cirrhotic patient.

PMID- 11999010
TI  - Management of oesophageal carcinoma with associated lung tuberculosis.

PMID- 11999011
TI  - Lung mucosal immunity: immunoglobulin-A revisited.

PMID- 11999012
TI  - Mosquitoes and soft ticks cannot transmit Lyme disease spirochetes.

PMID- 11999013
TI  - Ultrastructure of the spermatozoon of the pseudophyllidean cestode Eubothrium
      crassum (Bloch, 1779).
AB  - The fine structure of the mature spermatozoon of the pseudophyllidean tapeworm
      Eubothrium crassum, a parasite of salmonid fishes, has been studied by
      transmission electron microscopy for the first time. The mature spermatozoon of
      E. crassum is filiform and tapered at both extremities. It contains two axonemes
      of unequal length showing the 9 + "1" pattern of Trepaxonemata. The anterior
      extremity exhibits a crested body 50-100 nm thick. It spirals around the outside
      of the anterior region of the spermatozoon. The nucleus is electron-dense,
      exhibiting a fibrous appearance in its middle (the broadest) region. The cortical
      microtubules are of two types and are situated parallel to the spermatozoon axis.
      The cytoplasm is slightly electron-dense and contains numerous electron-dense
      granules in region II of the spermatozoon. A ring of electron-dense, centred
      microtubules surrounds the axoneme, together with the underlying ring of
      moderately electron-dense, subjacent submicrotubular material in region V. The
      anterior and posterior extremities of the spermatozoon lack cortical microtubules
      and contain a single axoneme. Our results reveal several peculiarities, in which
      the spermatozoon of E. crassum differs from those of other pseudophyllidean
      cestodes.

PMID- 11999014
TI  - Characterization of cDNA clones encoding ribonucleoprotein antigens expressed in
      Trypanosoma cruzi amastigotes.
AB  - Sera from patients with Chagas' disease were used to screen a Trypanosoma cruzi
      amastigote cDNA library. Characterization of 50 positive clones showed that 21
      (42%) encode previously identified T. cruzi ribosomal and flagellar proteins,
      heat-shock proteins or proteins with repetitive motifs. Twenty-nine clones (58%)
      correspond to nine genes not previously described in T. cruzi. Three cDNAs,
      encoding novel repetitive antigens with homology to ribosomal proteins and to
      other RNA binding proteins, were further characterized. Patient humoral responses
      against the recombinant proteins encoded by these cDNAs were evaluated in
      anticipation that they may constitute potential new targets for serodiagnostic
      assays.

PMID- 11999015
TI  - Development of Eimeria bovis in vitro: suitability of several bovine, human and
      porcine endothelial cell lines, bovine fetal gastrointestinal, Madin-Darby bovine
      kidney (MDBK) and African green monkey kidney (VERO) cells.
AB  - Several bovine, human and porcine endothelial cell lines, bovine fetal
      gastrointestinal cells (BFGC), Madin-Darby bovine kidney (MDBK) and African green
      monkey kidney (VERO) cells were exposed in vitro to sporozoites of Eimeria bovis.
      Parasites invaded all cells used and changed their shape to more stumpy forms
      within 12 h. Sporozoites left their host cells and invaded new ones frequently
      within the first 12 h post-infection. Further development took place only in
      bovine cells, although parasites survived in the other cells for at least 3
      weeks. Within the non-bovine cells, conspicuously enlarged parasitophorous
      vacuoles developed in VERO cells and reached a diameter of 15-20 microm. The best
      development to first generation schizonts with regard both to time required to
      mature, to schizont size and to merozoite yields was observed in BFGC, followed
      by bovine umbilical vein and bovine spleen lymphatic endothelial cells. MDBK
      cells were less suitable. The life cycle was completed (development of oocysts)
      only occasionally in BFGC. Results are considered under several aspects. Thus,
      infected VERO cells may represent a suitable tool for studying the
      parasitophorous vacuole, while infected endothelial cells represent a system
      quite narrow to the in vivo situation and should allow basic studies on
      parasite/host cell interactions and BFGC can be used for the mass production of
      E. bovis first generation merozoites.

PMID- 11999016
TI  - Production of monoclonal antibodies using an electrophoretically separated
      diagnostic marker from the urine of individuals infected with Schistosoma
      japonicum.
AB  - In this paper, electrophoresis was successfully used to screen a diagnostic
      marker (a glycoprotein of 30 kDa) from the urine of individuals infected with
      Schistosoma japonicum, and then with the marker as antigen, two lines of
      monoclonal antibodies (mAbs) were obtained, NP56 and NP54. NP56 was of better
      immunoreactivity, its immunoglobulin isotype being IgG2b. NP56 reacted with
      soluble egg antigen and adult worm antigen and miracidia in eggs of S. japonicum.
      Using NP56 as a probe in indirect ELISA, the sensitivity and specificity (median
      egg excretion per gram of feces 69) was 90% and 100% in concentrated urine
      samples and 50% and 100% in original urine samples, respectively. The results
      indicate that the method is feasible for producing mAbs with diagnostic markers
      separated electrophoretically from the urine of individuals infected with
      pathogen.

PMID- 11999017
TI  - Difficulties in the genetic interpretation of isozyme patterns of Lecithochirium
      spp. (Trematoda: Digenea).
AB  - Isozyme variation in adenosine deaminase (ADA) and glutamate-oxalacetate
      transaminase (GOT) was examined in 401 individuals of Lecithochirium rufoviride
      and Lecithochirium fusiforme from Conger conger. The banding patterns obtained
      for ADA were consistent with a monomeric structure and with single-locus control.
      This enzyme was polymorphic in the population, with two allozymes being detected.
      However an additional band, which may correspond to a secondary isozyme, was also
      observed. In accordance with this interpretation, ADA showed a significant
      departure from Hardy-Weinberg predictions associated with heterozygote
      deficiencies. Only one activity zone for GOT was detected in a subset of
      individuals, whereas some specimens showed a second weakly stained band, which
      may have been due to host enzyme contamination, although other possible reasons
      are also discussed. The electrophoretic patterns for ADA and GOT in these species
      provide examples of how some problems in electrophoretic analysis, such as
      nonheritable variation, may lead to the misinterpretation of zymograms in
      systematic and population genetic studies of parasites.

PMID- 11999018
TI  - Fasciola gigantica: tegumental surface alterations following treatment in vitro
      with the sulphoxide metabolite of triclabendazole.
AB  - The effect of the active sulphoxide metabolite of the fasciolicide
      triclabendazole on the surface morphology of the tropical liver fluke, Fasciola
      gigantica, was determined in vitro by scanning electron microscopy. At a
      concentration of 10 microg/ml, swelling and blebbing of the tegument was evident
      after only 6 h incubation. The blebbing was focussed on the spines. With
      progressively longer incubation periods, blebbing on the spines became more
      severe, leading to tegumental sloughing and spine loss. Tegumental loss became
      more widespread and, after incubation periods of 18 h and 24 h in vitro,
      perforations of the basal lamina were evident and, in some cases, holes
      penetrated through the entire fluke in the tail region. The ventral surface was
      consistently more severely affected than the dorsal and similarly the posterior
      region of the fluke was more disrupted than the anterior region. The results
      confirm the potent activity of triclabendazole against F. gigantica.

PMID- 11999019
TI  - Using flow cytometry to determine the viability of Cryptosporidium parvum oocysts
      extracted from spiked environmental samples in chambers.
AB  - Cryptosporidium parvum oocyst viability was determined by a dye permeability
      assay using a flow cytometric method. Oocysts were inoculated into small chambers
      with soil and biosolids. Oocysts extracted from soil and biosolids were then
      stained with propidium iodide (PI) and labeled with a fluorescein isothiocyanate
      (FITC)-conjugated monoclonal antibody. The oocyst population in each sample was
      determined using forward and side scatter plots, then further analyzed with
      fluorescence. A red and green fluorescence detector using gates established
      single populations of unstained, PI-stained, or FITC-labeled oocysts. No
      statistical difference was observed between viability of oocysts extracted from
      soil and biosolids as determined by either flow cytometry or microscopy. The
      location of excysted oocysts was changed in forward and side scatter plots.
      Results indicated that, although oocysts are not identified if they excyst, the
      flow cytometric method could be used to determine oocyst viability from spiked
      environmental samples.

PMID- 11999020
TI  - Expression and processing of megasome cysteine proteinases during Leishmania
      amazonensis differentiation.
AB  - Amastigotes of Leishmania species belonging to the Leishmania mexicana complex
      exhibit large lysosomes, called megasomes, which are rich in cysteine
      proteinases. Various aspects of the host-parasite interaction, the
      differentiation process as well as intracellular survival, have been attributed
      to these proteinases. The in vitro differentiation from promastigote to
      amastigote forms of Leishmania amazonensis was evaluated using the analysis of
      the expression of cysteine proteinase (Lpcys2) by Northern blot, Western blot and
      enzymatic activity. As promastigotes transformed to amastigotes, there was an
      increase in Lpcys2 RNA transcription, as well as an increase in Lpcys2 production
      and activity. Moreover, the processing rate of the cysteine proteinase precursor
      forms was also increased in amastigote forms. These results are in agreement with
      our previous study in which megasome development was demonstrated by morphometric
      and immunochemical analysis.

PMID- 11999021
TI  - Specific IgA response, T-cell subtype and cytokine profile in experimental
      intravaginal trichomoniasis.
AB  - Trichomoniasis caused by Trichomonas vaginalis may lead to either a complete
      absence of symptoms or to severe inflammatory manifestations in infected women.
      Studies of the role of immune responses in the pathogenesis and varied
      symptomatology of this disease are lacking. Mice may prove useful as an
      experimental model for intravaginal trichomoniasis in developing an understanding
      of the role of local immune responses in the pathogenesis and varied
      symptomatology of this disease. The present study reports the levels of anti
      Trichomonas IgA antibodies in serum and vaginal washes, and T-cell subtype and
      cytokine profile in vaginal cervical tissues of mice infected intravaginally with
      T. vaginalis isolates from 15 symptomatic and 15 asymptomatic women. It also
      correlates the responses with symptomatology of the patients. Successful
      intravaginal infection was established by inoculating T. vaginalis in BALB/c mice
      preinoculated with Lactobacillus acidophilus and pretreated with oestradiol. A
      significant increase in specific IgA antibody levels was detected with enzyme
      linked immunosorbent assay in vaginal secretions and serum samples collected on
      the 7th post-infection day from animals infected with isolates from asymptomatic
      women when compared with mice infected with isolates from symptomatic women. T
      cell subset analysis showed significant differences, with increased CD4+ T-cell
      count in animals infected with isolates from asymptomatic women compared with
      animals infected using isolates from symptomatic women. No difference in CD8+ T
      cells was observed between the two groups. Cytokine profile revealed
      significantly higher (P < 0.001) production of gamma-IFN and IL-2 in mice
      infected with asymptomatic isolates compared with animals infected with
      symptomatic isolates, using T. vaginalis crude antigen extract and nonspecific
      mitogen (ConA) as stimulants for vaginal cervical lymphocytes. However, no
      difference in IL-4 levels was observed in the two groups of animals. In contrast,
      significant increase in tumour necrosis factor (TNF-alpha) levels was observed in
      animals infected with asymptomatic isolates compared with those infected with
      isolates from symptomatic women and controls, thereby indicating that TNF-alpha
      may play an important role in the inflammatory response to trichomoniasis. The
      study further suggests that specific IgA antibodies might help to protect
      asymptomatic individuals from severe infection and T-lymphocytes may play an
      important function in the eradication of the parasite. The cytokine profile
      indicated the involvement of Th-1 like responses in mice infected with
      asymptomatic isolates, compared with those infected with symptomatic isolates.

PMID- 11999022
TI  - Variation in murid Plasmodium desequestration and its modulation by stress and
      pentoxifylline.
AB  - Changes in the parasitaemia and the characteristics of parasitic infection for
      three species of rodent Plasmodium (P. chabaudi chabaudi, P. vinckei petteri and
      P. yoelii yoelii) were investigated under conditions of stress and after
      treatment with pentoxifylline (POF), a drug that increases red blood cell
      deformability and causes peripheral vasodilatation. The results indicated that
      under stress, late parasite stages became less abundant in the tail blood of
      mice. These changes might be the consequence of parasite sequestration. Attempts
      to assess sequestration intensity were made by measuring the release rate (RR) of
      late stages for 10,000 red blood cells. The RR is given by the product of the
      parasitaemia (P) by the percentage of old trophozoites (OT) and schizonts (S) in
      the peripheral blood: RR = P(%OT + %S) . With all three species, RR decreased
      considerably within 5 min following the manipulation of the mice. Injections of
      POF had the opposite effect. POF had a protective effect against infection by
      P.v. petteri, causing a delay of 48 h in the development of infection and a
      higher survival rate in treated mice.

PMID- 11999023
TI  - Interleukin-5 transgenic mice show augmented resistance to Angiostrongylus
      costaricensis infection.
AB  - To determine the possible role of eosinophils in Angiostrongylus costaricensis
      infection, both interleukin-5 (IL-5) transgenic (Tg) and non-transgenic (non-Tg)
      C3H/HeN mice were infected with A. costaricensis third-stage larvae. IL-5 Tg mice
      demonstrated greater resistance than non-Tg mice to A. costaricensis, as shown by
      lower adult worm recovery, smaller adults, fewer eggs in the intestinal wall and
      fewer larvae passed in the feces. Both mice showed similar antigen-specific IgA
      and IgGI antibody responses, although IgA was more prominent than IgG1. Egg
      deposition and inflammatory responses in the intestinal walls were milder in IL-5
      Tg mice than in non-Tg mice. The eggs with developed larvae, deposited in the
      intestinal walls of IL-5 Tg mice, were surrounded by numerous degranulating
      eosinophils and sometimes with Splendore-Hoeppli deposits. The data suggest that
      eosinophils are involved in the resistance of the mouse during primary infection
      with A. costaricensis.

PMID- 11999024
TI  - Scanning electron microscopy in the investigation of the in vitro hemolytic
      activity of Trichomonas vaginalis.
AB  - The in vitro hemolytic activity of Trichomonas vaginalis has been previously
      demonstrated, but the mechanisms involved remain to be elucidated. In this work
      we used scanning electron microscopy to investigate the contact dependency of the
      hemolytic phenomenon caused by the parasites. The erythrocytes adhered to the
      parasites' surface and were phagocytosed. These observations suggest that the
      contact between T. vaginalis and erythrocytes may be an important mechanism in
      the injury caused to the erythrocytes. The hemolytic activity of T. vaginalis may
      be an efficient means of obtaining nutrients for the parasite and allow the
      investigation of the mechanism used by T. vaginalis to damage cellular membranes.

PMID- 11999025
TI  - Notes on coccidian phylogeny, based on the apicoplast small subunit ribosomal
      DNA.
AB  - We performed a phylogenetic analysis, based on the partial small subunit rRNA
      gene (SSU rRNA) sequences from 13 apicoplasts (including new sequences of
      Sarcocystis muris and Hyaloklossia lieberkuehni) and 16 other plastids, with
      cyanobacteria as an outgroup. The apicoplast sequences formed a highly supported
      monophyletic clade with two distinct clades, representing coccidia and
      haemosporidia, with coccidia divided into Eimeriidae and Sarcocystidae subclades.
      We confirmed the phylogenetic position of H. lieberkuehni within the
      Sarcocistidae, as a sister to the Toxoplasma/Neospora group. The coccidian
      plastid sequences appear to evolve slowly, while their homologues from
      haemosporidians are more rapidly evolving. We suggest that the higher
      evolutionary rate is reflected by the increase in the AT content and the possible
      reduction of the outer apicoplast membrane in some haemosporidians. Since the
      apicoplast SSU rRNA gene sequences, when compared with their nuclear homologues,
      offer a higher number of informative positions, they can be used for phylogenetic
      inference within the Apicomplexa.

PMID- 11999026
TI  - Fasciola gigantica: the growth and larval productivity of redial generations in
      the snail Lymnaea truncatula.
AB  - Bimiracidial infections of French Lymnaea truncatula with a Madagascan isolate of
      Fasciola gigantica were carried out under laboratory conditions to study the
      growth of rediae and their larval productivity in relation to the different
      redial generations. The total numbers of rediae and their mean lengths
      significantly increased with the duration of infection until day 49 post-exposure
      (p.e.). Significant differences in the lengths between the different redial
      generations were noted. At day 49 p.e. (at 20 degrees C), the cercariae were
      produced by the first redial generation, while the productivity of other redial
      groups was delayed. This last finding shows a slow larval development of this
      Madagascan isolate of F. gigantica in this French population of L. truncatula.

PMID- 11999027
TI  - Species-restricted antibody response against a DNA-construct coding for aspartic
      proteinase from Schistosoma japonicum.
AB  - DNA-based vaccine technology was used to immunize against the schistosome
      digestive enzyme, cathepsin D aspartic proteinase. The cDNA coding for
      Schistosomajaponicum aspartic proteinase was cloned in a mammalian expression
      vector under control of the CMV promoter/enhancer and expressed for the first
      time in transfected mammalian cells as well as in mice immunized--by means of
      intra-ear pinna injection--with the aspartic proteinase-encoding DNA construct.
      Mice developed antibodies which recognized the native protein in homogenates of
      S. japonicum worms and reacted with the gut and, to a much lesser degree, with
      the parenchyma of the parasites in cryostat sections. It was noteworthy that the
      vaccinated mouse sera did not detectably cross-react with S. mansoni antigens
      either in homogenates or on cryostat sections. By contrast, infection sera of
      mice or humans strongly cross-reacted with both schistosome species. We conclude
      that DNA vaccination can induce species-restricted antibody responses against
      schistosome proteins. The implications of this previously unrecognized
      specificity are discussed.

PMID- 11999028
TI  - The mitochondrial 12S gene is a suitable marker of populations of Sarcoptes
      scabiei from wombats, dogs and humans in Australia.
AB  - We sequenced part of the mitochondrial 12S ribosomal RNA gene of 23 specimens of
      Sarcoptes scabiei from eight wombats, one dog and three humans. Twelve of the 326
      nucleotide positions varied among these mites and there were nine haplotypes
      (sequences) that differed by 1-8 nucleotides. Phylogenetic analyses indicated
      that these mites were from two lineages: (1) mites from wombats from Victoria,
      Australia, and mites from the humans and dog from the Northern Territory,
      Australia (haplotypes 1-4, 9); and (2) mites from the humans and dog from the
      Northern Territory (haplotypes 5-8). Mites from the three different hosts
      (wombats, a dog and humans) had not diverged phylogenetically; rather, these
      mites had similar 12S sequences. Thus, we conclude that these mites from wombats,
      humans and a dog are closely related, and that they diverged from a common
      ancestor relatively recently. This conclusion is consistent with the argument
      that people and/or their dogs introduced to Australia the S. scabiei mites that
      infect wombats in Australia . So, S. scabiei, which has been blamed for the
      extinction of populations of wombats in Australia, may be a parasitic mite that
      was introduced to Australia with people and/or their dogs. These data show that
      the mitochondrial 12S rRNA gene may be a suitable population marker of S. scabiei
      from wombats, dogs and humans in Australia.

PMID- 11999029
TI  - Cattle near the Bwindi Impenetrable National Park, Uganda, as a reservoir of
      Cryptosporidium parvum and Giardia duodenalis for local community and free
      ranging gorillas.
AB  - The prevalence and intensity of shedding of Cryptosporidium parvum oocysts and
      Giardia duodenalis cysts was investigated in cattle grazing in the vicinity of
      the Bwindi Impenetrable National Park, Uganda. The prevalence of
      cryptosporidiosis and giardiosis was 38% and 12%, respectively, with 10%
      concomitant infections. Shedding intensity varied from 130 to 450 oocysts/g (mean
      of 215 oocysts/g) and from 110 to 270 cysts/g (mean of 156 cysts/g).
      Significantly more pre-weaned than post-weaned cattle were infected with either
      parasite, and the pre-weaned cattle shed significantly higher numbers of either
      parasite than the post-weaned cattle. Mathematical modeling indicated that the
      maximum prevalence of asymptomatic infections can reach approximately 80% for
      cryptosporidiosis and 35% for giardiosis in the sampled cattle. Because C. parvum
      and G. duodenalis recovered from cattle can infect people and gorillas, cattle
      that graze within the Bwindi Park should be considered as a significant reservoir
      of these anthropozoonotic parasites.

PMID- 11999030
TI  - Highland populations of Lymnaea truncatula infected with Fasciola hepatica
      survive longer under experimental conditions than lowland ones.
AB  - A retrospective study was carried out on the experimental infections of Lymnaea
      truncatula with Fasciola hepatica performed over the last 20 years to determine
      if the populations of snails living in highland or lowland countries had the same
      ability to sustain trematode larval development. The six highland populations
      originated from the Peruvian Altiplano (altitude 2,800 m), the French Alps (2,300
      m), and the Massif Central (900-1,400 m), whereas the 13 lowland populations came
      from different sites located in central France (90-250 m). Bimiracidial
      infections of 4-mm-high snails were performed to study cercarial shedding and to
      quantify their redial burden. Compared to lowland populations, snail survival at
      day 30 post-exposure was significantly higher in the highland L. truncatula (57
      75% compared to 31-45%) and their lifespan was greater (a mean of 87-96 days for
      cercaria-shedding snails compared to 64-77 days). The prevalences of F. hepatica
      infections, the numbers of free rediae within snail bodies, and the numbers of
      cercariae did not show any significant differences between highland and lowland
      snails although the numbers of cercariae were clearly higher in the Peruvian and
      three French highland populations of L. truncatula. The long survival times of
      highland snails under laboratory conditions might be an adaptation of these L.
      truncatula to the more extreme highland climate. The better ability of highland
      snails to sustain parasite larval development suggests that they would be better
      intermediate hosts in the life cycle of F. hepatica than lowland populations.

PMID- 11999031
TI  - Precautionary conflict.

PMID- 11999032
TI  - Bioterrorism and water security.

PMID- 11999033
TI  - Polar sunrise provides clues to dynamic mercury cycle.

PMID- 11999034
TI  - Treated wood linked to aquatic damage.

PMID- 11999035
TI  - Taiwan questions need for incinerators.

PMID- 11999036
TI  - Mapping out the Populus genome.

PMID- 11999037
TI  - Fiscal year 2003 budget.

PMID- 11999038
TI  - Fluorescence excitation-emission matrix characterization of river waters impacted
      by a tissue mill effluent.
AB  - Fluorescence excitation-emission matrix (EEM) spectrophotometry was applied to
      five neighboring rivers, including one that is impacted by wastewater from a
      large tissue mill, to determine if fluorescence spectrophotometry could be used
      to differentiate between the river waters. River water samples from both the
      tissue mill effluent and the impacted river, the Park Burn, exhibited
      significantly higher fluorescence intensity than the other sites. This
      fluorescence was dominated by tryptophan fluorescence and a fluorescence center
      possibly due to the presence of fluorescent whitening agents. In contrast, the
      three other rivers exhibited lower fluorescence intensities typical of river
      systems with tryptophan (sewage), humic-like (peat derived color), and fulvic
      like (natural organic matter) sources. It is suggested that fluorescence EEM
      spectrophotometry has the potential to provide a useful tool for pollution
      detection, monitoring, and control of paper industry impacts on river systems.

PMID- 11999039
TI  - Mercury and lead budgets for Lochnagar, a Scottish mountain lake and its
      catchment.
AB  - Lochnagar is a mountain lake located to the southeast of the Cairngorm Mountains
      in Scotland. The inputs and outputs of Hg and Pb and their distribution within
      the various ecosystem compartments were measured. Further, 17 sediment cores and
      10 catchment peat cores were taken and dated using spheroidal carbonaceous
      particle (SCP) and 210Pb techniques. Total and anthropogenic Hg and Pb
      inventories since the 1860s for the lake basin and the catchment peats were
      calculated using this multiple core strategy. Hg sediment flux profiles based on
      the whole lake basin show that the flux to the sediments increased from the 1880s
      until the 1970s. This was followed by a relatively stable period (1970s to the
      present), during which the flux was approximately twice that of the 1880s.
      Similarly, the Pb flux increased from the 1860s until the 1940s and was also
      followed by a relatively stable period through to the present. Hg and Pb budgets
      for the whole catchment for 1998 indicated that 78% of the Hg and 91% of the Pb
      input to the lake were transported from the catchment. Hence, the expected
      decline resulting from the decrease in the atmospheric deposition of Pb was
      obscured in the sediment record. It is estimated that 77% of the total Hg and 90%
      of the total Pb deposited since the 1860s, and stored in the upper layers of the
      catchment peat soils, are from anthropogenic sources. The increased storage of Hg
      and Pb in the catchment implies that this will be a major source of these metals
      for the lake for many years. This will delay the restoration of the lake system,
      despite reductions in emissions to the atmosphere and subsequent deposition.

PMID- 11999040
TI  - Speciated ambient carbonyls in Rio de Janeiro, Brazil.
AB  - Carbonyls in urban air continue to receive scientific and regulatory attention as
      toxic air contaminants and for their important role in photochemical smog.
      However, few data are available for speciated carbonyls in urban air. Ambient
      concentrations of up to 61 carbonyls have been measured in Rio de Janeiro,
      Brazil. The most abundant carbonyls were formaldehyde and acetaldehyde (study
      averaged concentrations of 10.8 +/- 4.1 and 10.4 +/- 4.6 microg m(-3),
      respectively, in samples of 3-h duration collected from May to November 2000 at a
      downtown location during the morning vehicle commute) followed by acetone, 2
      butanone, and benzaldehyde. Ambient concentrations of other carbonyls (except
      acetophenone) correlated well with those of acetaldehyde and of formaldehyde.
      This study examines the ambient acetaldehyde/ambient formaldehyde concentration
      ratio in Brazilian cities since the mid-1980s in the context of changes in
      Brazil's reliance on ethanol as a vehicle fuel. This ratio has begun to decrease
      in recent years due to fleet turnover and is likely to decrease further as older
      cars fueled with ethanol are replaced by lower-emitting models that run on a
      gasoline-ethanol blend. The carbonyls measured are ranked with respect to ozone
      formation potential (using MIR coefficients) and reaction with OH (using carbonyl
      OH reaction rate constants). Ozone formation is dominated by formaldehyde (43% of
      total) followed by acetaldehyde (32%) and methylglyoxal (8%); other carbonyls
      each contributed < or = 4% of total. For reaction with OH, acetaldehyde ranks
      first closely followed by formaldehyde.

PMID- 11999041
TI  - "Red-tide" cells up close.

PMID- 11999042
TI  - Seasonal variation of persistent organochlorine accumulation in birds from Lake
      Baikal, Russia, and the role of the south Asian region as a source of pollution
      for wintering migrants.
AB  - Concentrations of persistent organochlorines (OCs) such as polychlorinated
      biphenyls (PCBs), DDT and its metabolites (DDTs), hexachlorocyclohexane isomers
      (HCHs), and chlordane compounds (CHLs) were determined in whole body soft tissue
      homogenates and in muscles of resident and migratory birds collected from Lake
      Baikal, Russia. The residue pattern in both resident and migratory birds was in
      the following order: PCBs > DDTs > HCHs > CHLs. OC concentrations in migratory
      birds varied, depending on the feeding habit. The maximum levels of OCs were
      found in piscivores, followed by insectivores, omnivores, and herbivores. OC
      residue levels in Lake Baikal birds were lower than those in the Great Lakes
      region as well as in other lakes in Europe and Japan. Concentrations of HCHs and
      DDTs in most of the migratory birds collected in the spring were higher than for
      those collected in the autumn, indicating a notable accumulation in wintering
      grounds. Compilation and analysis of the available data in fish and birds from
      Asia suggested that the tropical and subtropical regions in south Asian countries
      may be a source of pollution for the wintering accumulation of migratory birds
      from Lake Baikal. Relatively higher compositions of alpha- and gamma-HCH in total
      HCHs, p,p'-DDT in total DOTs were observed in some migratory species, indicating
      recent exposure to HCHs and DDTs in Lake Baikal or wintering areas. PCB isomer
      patterns were different between residents and migrants, with the predominance of
      lower chlorinated congeners in migratory species, suggesting recent PCB
      accumulation in stopover sites during wintering. TEQ concentrations of toxic non-
      and mono-ortho coplanar PCBs in common terns from Lake Baikal were comparable to
      those reported in some species from Japan, the United States, and Europe.
      Relative contributions of non-ortho coplanar congeners to toxic equivalents
      (TEQs) were predominant, in which CB-126 accounted for the highest toxicity
      contribution. Estimated TEQ concentrations in the common tern from Lake Baikal
      exceeded the levels associated with enzyme induction in bald eagles. To our
      knowledge, this is the first comprehensive study showing the seasonal variations
      of OC accumulation in the birds from Lake Baikal.

PMID- 11999043
TI  - Fossil fuel and wood combustion as recorded by carbon particles in Lake Erie
      sediments 1850-1998.
AB  - Carbon particle analysis was performed on a dated sediment core from Lake Erie in
      order to explore the inputs of pollution from incomplete combustion of coal, oil,
      and wood. Carbon particles were isolated from the sediment by chemical digestion,
      and elemental carbon content was determined by CHN analysis. The type of carbon
      particle (from burning coal, oil, and wood) and particle size and relative
      abundance were determined using scanning electron microscopy on 100 particles
      from each core section. The elemental carbon content in the Lake Erie core ranges
      from 2.5 to 7.4 mg of carbon/g of sediment (1850-1998), and the maximum carbon
      content in the sediment occurs in the late 1960s to early 1970s. It is shown that
      particle mass is a better predictor than particle number of historical energy
      consumption records. This is especially clear for wood where variable particle
      volumes play a significant role in determining the record of elemental carbon
      mass from wood burning. Lake Erie core's content of total carbon and carbon
      particle type is in agreement with U.S. energy consumption records, except that a
      wood maximum occurs during 1905-1917, about 36 yr after the U.S. consumption
      maximum from 1870 to 1880.

PMID- 11999044
TI  - Analyzing the ignored environmental contaminants.

PMID- 11999045
TI  - Brominated flame retardants in archived serum samples from Norway: a study on
      temporal trends and the role of age.
AB  - The temporal trends and influence of age and gender on levels of selected
      brominated flame retardants (BFRs) in human serum have been assessed by analyzing
      archived samples from Norway. Serum from 40 to 50 year old men collected at six
      time periods during 1977 to 1999 and from eight groups of differing age and
      gender sampled in 1998 were pooled into six and eight samples, respectively. The
      BFRs were isolated using solid-phase extraction (SPE) and the serum lipids
      decomposed bytreatmentwith concentrated sulfuric acid directly on the polystyrene
      divinylbenzene SPE column, prior to elution of the BFRs. Following diazomethane
      derivatization, the samples were analyzed by gas chromatography-electron capture
      mass spectrometry. Eight BFRs were quantified in the serum samples: 2,4,4'
      tribromodiphenyl ether (BDE-28), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47),
      2,2',4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4',6-pentabromodiphenyl
      ether (BDE-100), 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153), 2,2',4,4',5,6'
      hexabromodiphenyl ether (BDE-154), 2,4,6-tribromophenol (TriBP), and
      tetrabromobisphenol A (TBBP-A). The serum concentrations of all the BFRs,
      increased during the entire period with the exception of TriBP, and the sum of
      the six polybrominated diphenyl ethers increased from 0.44 ng/g lipids in 1977 to
      3.3 ng/g lipids in 1999. The BFR concentrations in the serum from the different
      age groups were relatively similar, except for the age group 0-4 years, which had
      1.6-3.5 times higher serum concentrations. Women older than 25 years had lower
      serum concentrations of BFRs compared to the corresponding group of men. No trend
      related to age or gender, nor time during the period 1977 to 1999 was observed
      for TriBP. The present study indicates an ongoing increase in human exposure to
      BFRs, and the current body burden appears to be independent of age, except for
      infants (0-4 years old), who seem to experience elevated exposure.

PMID- 11999046
TI  - Enantiomer-specific accumulation of PCB atropisomers in the bowhead whale
      (Balaena mysticetus).
AB  - Blubber (n = 40) and liver (n = 20) samples from the bowhead whale (Balaena
      mysticetus) were collected during the 1997-1998 Native (Inuit) subsistence
      harvests in Barrow, AK. Bowhead tissues and zooplankton were analyzed for
      polychlorinated biphenyl (PCB) concentrations and the enantiomeric fractions
      (EFs) of eight chiral PCB congeners (PCB-91, 95, 135, 136, 149, 174, 176, and
      183) to quantify the enantiomer-specific accumulation of PCBs in this cetacean.
      PCB concentrations in bowhead blubber were low (mean +/- 1 SE: 610 +/- 54 ng g(
      1) lipid) relative to other cetaceans. The accumulation of several chiral PCBs
      (PCB-91, 135, 149, 174, 176, and 183) in bowhead blubber was enantiomer-specific
      relative to bowhead liver and zooplankton, suggesting that biotransformation
      processes within the bowhead whale are enantioselective. The EFs for PCB-95 and
      149 were significantly correlated with body length in male and female whales,
      while EFs for PCB-91 correlated with length in males only. Despite evidence for
      enantioselective biotransformation, all three congeners bioaccumulated in the
      bowhead relative to PCB-153. Results suggest that enantioselective accumulation
      of PCB-91, 95, and 149 is influenced by PCB concentrations, age, and/or the
      modification of an uncharacterized stereoselective process (or processes) during
      sexual maturity.

PMID- 11999047
TI  - Air-surface exchange of polybrominated diphenyl ethers and polychlorinated
      biphenyls.
AB  - Air and leaf-litter samples were collected from a rural site in southern Ontario
      under meteorologically stable conditions in the early spring, prior to bud burst,
      over a three-day period to measure the simultaneous diurnal variations in
      polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs).
      PBDEs are used in a wide range of commercial products as flame retardants and are
      being assessed internationally as potential persistent organic pollutants. Total
      PBDE concentrations in the air ranged between 88 and 1250 pg m(-3), and were
      dominated primarily by the lighter congeners PBDEs 17, 28, and 47, and
      concentrations of total PCBs ranged between 96 and 950 pg m(-3), and were
      dominated by the lower chlorinated (tri- to tetra-) congeners. Slopes of Clausius
      Clapeyron plots indicate that both PCBs and PBDEs are experiencing active air
      surface exchange. Fugacities were estimated from concentrations in the air and
      leaf-litter and suggest near equilibrium conditions. Following the three-day
      intensive sampling period, 40 air samples were collected at 24-hour intervals in
      an attempt to evaluate the effect of bud burst on atmospheric concentrations.
      Total PBDE concentrations in the daily air samples ranged between 10 and 230 pg
      m(-3), and were dominated by the lighter congeners PBDE 17, 28, and 47, whereas
      concentrations of total PCBs ranged between 30 and 450 pg m(-3) during this
      period. It is hypothesized thatthe high PBDE concentrations observed at the
      beginning of the sampling period are the result of an "early spring pulse" in
      which PBDEs deposited in the snowpack over the winter are released with snowmelt,
      resulting in elevated concentrations in the surface and air. Later in the
      sampling period, following bud burst, PBDE concentrations in air fell to 10 to 20
      pg m(-3), possibly due to the high sorption capacity of this freshly emerging
      foliage compartment.

PMID- 11999048
TI  - Trace metal levels in uncontaminated groundwater of a coastal watershed:
      importance of colloidal forms.
AB  - Groundwater and surface water were collected using trace metal clean techniques
      from the upper glacial aquifer of West Neck Bay (Shelter Island) in eastern Long
      Island, NY, during the late spring and summer of 1999. The collection sites on
      Shelter Island are located in an area that is primarily residential and believed
      to have uncontaminated groundwater. Ultrafiltration was used to size-fractionate
      the dissolved (<0.45 microm) fraction into colloidal (1 kDa - 0.45 microm) and
      low molecular weight (<1 kDa) size pools. These fractions were analyzed for trace
      metals (Al, Ag, Cd, Cu, Mn, Pb, and Zn), organic carbon, and inorganic nutrients
      (NH4, NO3, PO4). The levels of metals and organic carbon in the groundwater were
      as low as those found in the open ocean, far removed from anthropogenic inputs.
      These findings corroborate the need to apply trace metal clean techniques in the
      determination of metal levels in uncontaminated groundwater. A significant
      fraction of dissolved metals (22-96%) and organic carbon (approximately 40%) in
      the groundwater and in surface waters of the Bay was found to be associated with
      colloids. The significance of the metal association with the colloidal fraction
      decreased in the order of Al > Cu > Ag > Zn = Cd = Mn and appeared to be
      dependent on the affinities of these metals for humic substances. In contrast,
      NO3 and NH4 were found to be almost entirely (approximately 98-99%) in the low
      molecular weight size fraction. Metal/aluminum and metal/carbon ratios measured
      in the colloids were similar to those reported for humic substances and
      significantly different from those of soils. This suggests that colloidal
      particles might originate from humic materials as opposed to purely inorganic
      minerals. These results indicate the need to consider the colloidal fraction in
      the fate and mobility of metals in groundwater and that, despite the low levels
      of organic matter (<50 microM of DOC) measured in groundwater, some groundwater
      colloids appear to be organic in nature.

PMID- 11999049
TI  - Chemical characterzation of fine particle emissions from the fireplace combustion
      of woods grown in the Southern United States.
AB  - The fireplace combustion of wood is a significant and largely unregulated source
      of fine particle pollution in the United States. Source apportionment techniques
      that use particulate organic compounds as tracers have been successful in
      determining the contribution of wood smoke to ambient fine particle levels in
      specific areas in California. To apply these techniques to the rest of the United
      States, the differences in emissions profiles between different wood smoke
      sources and fuel types should be resolved. To this end, a series of fireplace
      source tests was conducted on six fuel wood species found in the Southern United
      States to determine fine particulate emission factors for total mass, ionic and
      elemental species, elemental and organic carbon, and over 250 individual organic
      compounds. The wood species tested, chosen for their high abundance and
      availability in the Southern U.S. region, were yellow poplar, white ash,
      sweetgum, mockernut hickory, loblolly pine, and slash pine. The differences in
      the emissions of compounds such as substituted phenols and resin acids help to
      distinguish between the smoke from hardwood and softwood combustion.
      Levoglucosan, a cellulose pyrolysis product which may serve as a tracer for wood
      smoke in general, was quantified in the emissions from all the wood species
      burned. The furofuran lignan, yangambin, which was emitted in significant
      quantities from yellow poplar combustion and not detected in any of the other
      North American wood smokes, is a potential species-specific molecular tracer
      which may be useful in qualitatively identifying particulate emissions from a
      specific geographical area where yellow poplar is being burned.

PMID- 11999050
TI  - Modeling the inhibition of the bacteral reduction of U(VI) by beta-MnO2(s).
AB  - Pyrolusite (beta-MnO2(s)) was used to assess the influence of a competitive
      electron acceptor on the kinetics of reduction of aqueous uranyl carbonate by a
      dissimilatory metal-reducing bacterium (DMRB), Shewanella putrefaciens strain
      CN32. The enzymatic reduction of U(VI) and beta-MnO2(s) and the abiotic redox
      reaction between beta-MnO2(s) and biogenic uraninite (UO2(s)) were independently
      investigated to allow for interpretation of studies of U(VI) bioreduction in the
      presence of beta-MnO2(s). Uranyl bioreduction to UO2(s) by CN32 with H2 as the
      electron donor followed Monod kinetics, with a maximum specific reduction rate of
      110 M/h/10(8) cells/mL and a half-saturation constant of 370 microM. The
      bioreduction rate of beta-MnO2(s) by CN32 was described by a pseudo-first-order
      model with respect to beta-MnO2(s) surface sites, with a rate constant of 7.92 x
      10(-2) h(-1)/10(8) cells/mL. Uraninite that precipitated as a result of microbial
      U(VI) reduction was abiotically reoxidized to U(VI) by beta-MnO2(s), with
      concomitant reduction to Mn(II). The oxidation of biogenic UO2(s) coupled with
      beta-MnO2(s) reduction was well-described by an electrochemical model. However, a
      simple model that coupled the bacterial reduction of U(VI) and beta-MnO2(s) with
      an abiotic redox reaction between UO2(s) and beta-MnO2(s) failed to describe the
      mass loss of U(VI) in the presence of beta-MnO2(s). Transmission electron
      microscopy (TEM) and energy dispersive spectroscopy (EDS) revealed that the
      particle size and spatial distribution of the biogenic UO2(s) changed dynamically
      in systems with, as compared to without, beta-MnO2(s)). These observations
      suggested that the surface properties and localization of UO2(s) in relation to
      the cell and beta-MnO2(s) surfaces was an important factor controlling the
      abiotic oxidation of UO2(s) and, thus, the overall rate and extent of U(VI)
      bioreduction. The coupled model that was modified to account for the "effective"
      contact surface area between UO2(s) and beta-MnO2(s) significantly improved the
      simulation of microbial reduction of U(VI) in the presence of beta-MnO2(s).

PMID- 11999051
TI  - Mechanisms of selenate adsorption on iron oxides and hydroxides.
AB  - Selenate (SeO4(2-)) is an oxyanion of environmental importance because of its
      toxicity to animals and its mobility in the soil environment. It is known that
      iron(III) oxides and hydroxides are important sorbents for SeO4(2-) in soils and
      sediments, but the mechanism of selenate adsorption on iron oxides has been the
      subject of intense debate. Our research employed Extended X-ray absorption fine
      structure and attenuated total reflectance-Fourier transform infrared
      spectroscopies to determine SeO4(2-) bonding mechanisms on hematite, goethite,
      and hydrous ferric oxide (HFO). It was learned that selenate forms only inner
      sphere surface complexes on hematite but forms a mixture of outer- and inner
      sphere surface complexes on goethite and HFO. This continuum of adsorption
      mechanisms is strongly affected by both pH and ionic strength. These results
      suggest that adsorption experiments should be conducted on several different iron
      oxides and over a wide range of reaction conditions to accurately assess the
      reactivity of oxyanions on iron oxides.

PMID- 11999052
TI  - Decomposition of hydrogen peroxide and organic compounds in the presence of
      dissolved iron and ferrihydrite.
AB  - This work examines the contribution of solution phase reactions, especially those
      involving a chain reaction mechanism, to the decomposition of hydrogen peroxide
      (H2O2) and organic compounds in the presence of dissolved iron and ferrihydrite.
      In solutions at pH 4, where Fe was introduced as dissolved Fe(III), both H2O2 and
      14C-labeled formic acid decomposed at measurable rates that agreed reasonably
      well with those predicted by a kinetic model of the chain reaction mechanism,
      using published rate constants extrapolated to pH 4. The ratio of the formic acid
      and H2O2 decomposition rates, as well as the dramatic effect of tert-butyl
      alcohol on these rates, confirmed that a solution chain reaction mechanism
      involving *OH controlled the decomposition kinetics of both compounds. In the
      presence of ferrihydrite as the iron source, the ratio of the rate of formic acid
      decomposition to that of H2O2 decomposition was significantly lower than that
      observed in the presence of only dissolved Fe. Moreover, neither rate diminished
      drastically upon addition of tert-butyl alcohol, indicating that the solution
      phase chain reaction is not a dominant decomposition pathway of H2O2 and formic
      acid. Relative decomposition rates of formic acid and a second *OH probe, benzoic
      acid, were consistent with oxidation of these compounds by *OH. These
      observations can be reproduced by a kinetic model including (a) decomposition of
      H2O2 at the iron oxide surface, producing *OH with lower yield than the reaction
      sequence with dissolved Fe, and (b) low concentrations of dissolved Fe in the
      presence of ferrihydrite, preventing propagation of the solution phase chain
      reaction.

PMID- 11999053
TI  - Perfluorochemical surfactants in the environment.

PMID- 11999054
TI  - Chemical speciation and toxicity of nickel species in natural waters from the
      Sudbury area (Canada).
AB  - Metal complexation properties of dissolved organic carbon (DOC) in freshwaters
      are recognized but poorly understood. Here, we investigated the release of free
      nickel from Ni-DOC complexes using nickel-polluted freshwaters from Sudbury
      (Canada). We used the Competing Ligand Exchange Method with Chelex-100 as the
      competing ligand to measure the rate of free Ni2+ ion released by the
      dissociation of Ni-DOC complexes. The kinetic studies showed that the fastest
      kinetically distinguishable component representing approximately 30-95% of the
      total nickel had a dissociation rate coefficient similar to that reported for
      [Ni(H20)6]2+. High concentrations of Ca2+ and Mg2+ caused a larger amount of the
      DOC-bound nickel to be released as free Ni2+ ion. Growth inhibition of the
      freshwater alga Pseudokirchneriella subcapitata was highly correlated with the
      Ni/DOC ratio, the free plus labile nickel concentration, and the dissociation
      rate coefficient. While the levels of metals were not sufficient to kill Daphnia
      magna, these test organisms were immobilized in the same samples that showed
      algal growth inhibition. Only one sample caused 22% death of Hydra attenuata. The
      algal toxicity tests were consistent with the kinetic speciation results and are
      consistent with the hypothesis that dissolved [Ni(H20)6]2+ plus other labile
      nickel species are toxic forms of Ni present.

PMID- 11999055
TI  - Heavy metal uptake by lignin: comparison of biotic ligand models with an ion
      exchange process.
AB  - Metal uptake by kraft lignin, hereafter referred to as lignin, occurs by
      displacement of protons or bound metals with equilibrium constants K(ex)H and
      K(ex), respectively. Values calculated for wide ranges of initial concentrations
      are reasonably constant, thereby demonstrating the validity of these displacement
      processes and proving that uptake in these systems is not simple adsorption. It
      was found that the stoichiometry for Sr and Cd uptake by Ca-loaded lignin is 1
      mol of metal for 1 mol of Ca released. This observation for metals of very
      different binding strengths is difficult to rationalize with the biotic ligand
      model as generally applied but is in complete agreement with an ion-exchange
      process. Binding strengths to lignin, which contains only oxygen ligands, follow
      the order Pb > Cu > Zn > Cd > Ca (strongest to weakest). For proton displacement,
      only more tightly bound metals such as Pb, Cu, Zn, and Cd can compete with
      protons for anion-binding sites at low pH, but at high pH, uptake of Ca, Sr, and
      Li can occur. An observed logarithmic decrease of K(ex)H with pH can be explained
      by having only weaker acids available for proton displacement under more basic
      conditions. The advantages and disadvantages of using adsorption and biotic
      ligand models for an ion-exchange process are discussed.

PMID- 11999056
TI  - In-situ evidence for uranium immobilization and remobilization.
AB  - The in-situ microbial reduction and immobilization of uranium was assessed as a
      means of preventing the migration of this element in the terrestrial subsurface.
      Uranium immobilization (putatively identified as reduction) and microbial
      respiratory activities were evaluated in the presence of exogenous electron
      donors and acceptors with field push-pull tests using wells installed in an
      anoxic aquifer contaminated with landfill leachate. Uranium(VI) amended at 1.5
      microM was reduced to less than 1 nM in groundwater in less than 8 d during all
      field experiments. Amendments of 0.5 mM sulfate or 5 mM nitrate slowed U(VI)
      immobilization and allowed for the recovery of 10% and 54% of the injected
      element, respectively, as compared to 4% in the unamended treatment. Laboratory
      incubations confirmed the field tests and showed that the majority of the U(VI)
      immobilized was due to microbial reduction. In these tests, nitrate treatment
      (7.5 mM) inhibited U(VI) reduction, and nitrite was transiently produced. Further
      push-pull tests were performed in which either 1 or 5 mM nitrate was added with
      1.0 uM U(VI) to sediments that already contained immobilized uranium. After an
      initial loss of the amendments, the concentration of soluble U(VI) increased and
      eventually exceeded the injected concentration, indicating that previously
      immobilized uranium was remobilized as nitrate was reduced. Laboratory
      experiments using heat-inactivated sediment slurries suggested that the
      intermediates of dissimilatory nitrate reduction (denitrification or
      dissimilatory nitrate reduction to ammonia), nitrite, nitrous oxide, and nitric
      oxide were all capable of oxidizing and mobilizing U(IV). These findings indicate
      that in-situ subsurface U(VI) immobilization can be expected to take place under
      anaerobic conditions, but the permanence of the approach can be impaired by
      disimilatory nitrate reduction intermediates that can mobilize previously reduced
      uranium.

PMID- 11999057
TI  - Effects of different quinoid redox mediators on the anaerobic reduction of azo
      dyes by bacteria.
AB  - The addition of quinoid redox mediators to anaerobically incubated cultures of
      various taxonomically different bacterial species resulted in significantly
      increased reduction rates for the azo dye amaranth. From different quinones
      tested, generally anthraquinone-2-sulfonate (AQS) and lawsone (2-hydroxy-1,4
      naphthoquinone) caused the highest increase in the azoreductase activities. The
      effects of AQS and lawsone were studied in greater detail with Sphingomonas
      xenophaga BN6 and Escherichia coli K12. Both strains reduced the quinones under
      anaerobic conditions with significantly different relative activities. The
      chemically reduced forms of AQS, lawsone, and different other quinones were
      assayed for their ability to decolorize amaranth, and a good correlation between
      the redox potentials of the quinones and the reduction rates of the azo dyes was
      observed. The addition of AQS or lawsone also increased the ability of
      unacclimated sewage sludge to reduce azo dyes. Chemically pure lawsone could be
      replaced by the powdered leaves of the henna plant which contain significant
      amounts of lawsone.

PMID- 11999058
TI  - Indicator to predict the movement of phosphorus from soil to subsurface flow.
AB  - The movement of phosphorus (P) in subsurface flow can contribute to losses from
      agricultural land. This study aims to identify a soil P threshold above which P
      loss is likely to accelerate as a function of soil and management type.
      Lysimeters (25 cm i.d. by 30 cm deep) were taken of four soils from agricultural
      watersheds in Pennsylvania and New York. The soils had a range of Mehlich-3
      extractable P (7-517 mg of P kg(-1)) in surface soil (0-7.5 cm for grassland and
      0-23 cm for cultivated/arable) and reactive P, filtered <0.45 microm (RP(<0.45
      microm) in subsurface flow (0.007-1.53 mg of P L(-1)). The loss of P from
      lysimeters increased greatly when Mehlich-3 extractable P was in excess of a mean
      concentration of 280 mg kg(-1), the degree of saturation of P sorption sites
      exceeded 38%, and the corrected P sorption strength (corrected for desorption)
      derived from the monolayer Langmuir equation was less than 0.07 L of P mg(-1). Of
      these variables, P sorption strength was most consistently related to RP(<0.45
      microm) in subsurface flow across a range of soil managements. Use of the
      corrected Langmuir sorption strength parameter to estimate subsurface flow
      RP(<0.45 microm) derived from four U.S. soils was tested on four soils of
      different physiochemical characteristics (one calcareous) from the U.K. The U.K.
      soils showed similar concentration trends to the U.S. soils, with elevated
      RP(<0.45 microm) below a sorption strength of 0.07 L of P mg(-1). We propose that
      the P sorption strength derived from the monolayer Langmuir equation may be used
      to estimate the potential for P loss in subsurface flow, when simpler
      environmental tests such as P saturation derived from acid ammonium oxalate
      extraction are unclear or unsuitable.

PMID- 11999059
TI  - Displacement effect of NOM on atrazine adsorption by PACs with different pore
      size distributions.
AB  - This study investigated displacement of atrazine by the strongly competing
      fraction of natural organic matter (NOM) in batch and continuous-flow powdered
      activated carbon/PAC) adsorption systems. Due to the displacement effect,
      atrazine adsorption capacity in a continuous flow PAC/microfiltration (MF)
      system, where the carbon retention time is greater than the hydraulic retention
      time, decreased with time or NOM throughput. The capacity was lower than that
      measured in a batch reactor or predicted by the equivalent background compound
      ideal adsorbed solution theory (EBC-IAST) method. A mathematical model previously
      developed to simulate the adsorption process in the PAC/MF system was modified to
      take into account the displacement effect. Two types of PACs were tested using a
      range of influent atrazine concentrations and carbon doses. The extent of
      atrazine displacement by NOM was found to depend on the type of PAC, while the
      rate of displacement was a function of PAC type as well as carbon dose. The PAC
      lost its adsorption capacity for atrazine faster at a lower carbon dose. PAC B,
      which has a higher percentage of mesopores, lost more atrazine adsorption
      capacity but at a slower rate than PAC A.

PMID- 11999060
TI  - Seasonal and interannual mobility of arsenic in a lake impacted by metal mining.
AB  - Detailed examination of the water column, sediments, and interstitial waters was
      conducted in Balmer Lake, Ontario, Canada, in 1993-1994 and 1999 in order to
      assess the seasonal and interannual controls governing the behavior of As. High
      resolution profiles of dissolved (<0.45 microm) Fe, Mn, SO4(2-), and sigmaH2S
      across the sediment-water interface indicate the presence of reducing conditions
      in close proximity to the benthic boundary during ice-free periods, which are
      characterized by fully oxygenated bottom waters. Dissolved As is remobilized as
      As(III) in suboxic sediment horizons via the redox-controlled dissolution of Fe
      (and perhaps Mn) oxide phases. During 1993-1994, As fluxes to the water column
      were relatively low (2-15 microg cm(-2) year(-1)) and contributed between 2 and
      18% of the water column inventory. Dissolved As in the lake waters was derived
      primarily from external mining-related loadings during this period. Between 1993
      and 1999, external loadings of As to Balmer Lake decreased while [As]aq within
      the lake increased, suggesting an increase in the proportion of sediment-derived
      As. Indeed, benthic dissolved As fluxes in 1999 ranged from 179 to 380 microg cm(
      2) year(-1), representing approximately 33-60% of the water column burden. The
      relatively recent importance of sedimentary arsenic sources is suggested to
      reflect changes to sediment redox conditions associated with a postulated
      increase in lake primary productivity. Ironically, the increased contribution of
      dissolved arsenic to the water column appears to have resulted from an otherwise
      improvement in water quality. Reduced loadings of Cu, Zn, and Ni to the lake
      since 1994 appear to have allowed increased phytoplankton production that has
      stimulated arsenic release.

PMID- 11999061
TI  - Experimental and molecular mechanics and ab initio investigation of activated
      adsorption and desorption of trichloroethylene in mineral micropores.
AB  - This research investigated activated adsorption of a hydrophobic organic
      contaminant(HOC) in mineral micropores using experimental and molecular modeling
      techniques. Adsorption of trichloroethylene (TCE) on a silica gel adsorbent was
      measured using a frontal analysis chromatography technique at atmospheric and
      elevated fluid pressures. Increasing the fluid pressure yielded increased TCE
      uptake that was not released upon lowering the pressure back to atmospheric
      conditions. This showed that the increase in pressure was able to rapidly induce
      the formation of a desorption-resistant fraction that previous investigations
      have shown requires months to develop at atmospheric pressure. Grand Canonical
      Monte Carlo (GCMC) modeling was then used to elucidate the nature of water and
      TCE behavior within silica micropores. The GCMC modeling showed that molecular
      scale packing restrictions resulted in pore fluid densities that ranged from 0.28
      to 0.78 of those in the bulk solution. The modeling also showed that TCE was able
      to displace water from hydrophilic mineral pores due to molecular scale packing
      restrictions. Exothermic isosteric heats for TCE adsorption up to -27 kJ/mol were
      observed and were greatest in pores of 7 and 8 A. This indicated that TCE
      adsorption was energetically most favorable in pores that were minimally large
      enough to accommodate a TCE molecule. The pressure-induced uptake appeared to
      result primarily from an increase in the packing density in the smallest pores.
      Ab initio calculations showed that small distortions of a TCE molecule from its
      low energy conformation require high activation energies. Results from this study
      indicate that activated adsorption requiring bond angle distortions in the
      adsorbate may be responsible forthe slow attainment of adsorptive equilibrium of
      HOCs on microporous solids. Likewise, activated desorption from molecular-sized
      adsorption sites may contribute to the slow release of HOCs from aquifer
      sediments.

PMID- 11999062
TI  - GIS-based system for surface water risk assessment of agricultural chemicals. 1.
      Methodological approach.
AB  - A methodology to develop a GIS-based system for the surface water risk assessment
      of agricultural chemicals is described. It is based on the integration of
      relational and spatial databases, GIS incorporating raster and vector, mass
      balance models, and pesticide risks indicators. Surface water pollution was
      modeled by taking into account two main processes: the load due to drift and the
      load due to a rainfall-runoff event. The former is immediately consequent to
      pesticide application; the second occurs a short period afterward. Thus two
      distinct PEC (predicted environmental concentration) values were estimated,
      differing in time. A pilot approach was applied to the herbicide alachlor on corn
      in Lombardia region (northern Italy) and represents the first stage of a wider
      project. Although the resultant alachlor PEC and risk maps represent a static
      image of a worst-case simulation, the main objective was to provide information
      for the territory with respect to relative risks at the watershed level, which is
      important in managing risks to the aquatic environment. The driving forces and
      spatial variability of the above-mentioned processes were investigated to improve
      knowledge about the territory and to indicate the need for more detailed site
      specific studies.

PMID- 11999063
TI  - Persistence of antifouling agents in the marine biosphere.
AB  - Risk indicators provide an interesting way to compare chemical substances with
      respect to the risks of their large-scaled release. The present study implies
      that, for antifouling agents used in commercial shipping, residence times in the
      marine biosphere are especially suitable to represent their inherent potential to
      cause exposure of organisms. A simple box model is described providing the
      possibility to estimate residence times in the marine biosphere from water
      particle equilibrium partitioning constants and half-lives in water and sediment.
      Resulting residence times in the marine biosphere range from about 5 d (4,5
      dichloro-2-n-octyl-4-isothiazolin-3-one) up to about 40,000 yr (copper). For an
      evaluation of the validity of the model, calculated values are compared with
      measured environmental concentrations. Remaining uncertainties are also
      discussed. The main purpose of the presented residence times is to serve as a
      basis for decisions in antifouling paint development or environmentally conscious
      purchasing of antifouling paints.

PMID- 11999064
TI  - Hg(II) adsorption by bacteria: a surface complexation model and its application
      to shallow acidic lakes and wetlands in Kejimkujik National Park, Nova Scotia,
      Canada.
AB  - The fate and environmental threat posed by mercury in aquatic systems is
      controlled, in part, bythe transport of Hg(II) from oxic to anoxic zones in lakes
      and its subsequent transformation to organic mercury. The transport of Hg(II) in
      aquatic systems can be affected by its partitioning between the dissolved and
      particulate phases. In this study, batch experiments were performed to quantify
      Hg(II) adsorption to Bacillus subtilis as bacteria-to-metal ratio, pH, chloride
      concentration, growth phase, and reaction time were independently varied. The
      laboratory data were well described by a surface complexation model (SCM)
      considering the adsorption of neutral Hg(II) hydroxide and chloride complexes by
      specific functional groups on the bacterial surface. To evaluate its
      applicability to complex aquatic systems, the SCM was used to predict the
      distributions of Hg(II) in 36 shallow acidic lakes and wetlands in Kejimkujik
      National Park, Nova Scotia, Canada. The lab-derived SCM provided a statistically
      accurate (r2 = 0.615, P < 0.01) fit to the field data when it was expanded to
      consider Hg(II) complexation by dissolved organic matter. Inclusion of Hg(II)
      mineral adsorption reactions did not improve the fit of the model. The quality of
      fit provided by the expanded SCM suggested that the major assumptions implicit in
      applying a lab-derived model to the field were justifiable. Our study has
      demonstrated that SCMs are powerful tools for dynamic prediction of the sorption
      of environmental contaminants to biocolloids at the regional scale.

PMID- 11999065
TI  - Magnetic resonance imaging in environmental science.

PMID- 11999066
TI  - Performance characteristics and applications of a proton transfer reaction-mass
      spectrometer for measuring volatile organic compounds in ambient air.
AB  - Data illustrating the performance characteristics of a proton transfer reaction
      mass spectrometer (PTR-MS) under both laboratory and field conditions are
      presented. Under laboratory conditions, we demonstrate that PTR-MS measures
      (within 10%) a 2.6 ppbv concentration of gaseous dimethyl sulfide. Using a
      stepwise dilution of a gaseous isoprene standard, we demonstrate the linearity of
      the response of PTR-MS across 3 orders of magnitude of mixing ratios, from 100
      ppbv to less than 100 pptv. By combining this data set with that of its
      monosubstituted 13C isotopic analogue, we demonstrate the ability of the
      instrumentto reliably measure concentrations as low as approximately 50 pptv and
      to detect concentrations at significantly lower levels. We conclude our
      laboratory characterization by investigating the components of the instrument
      noise signal (drift, mean, and range) and develop an expression (noise statistic)
      that reliably predicts the instrumental noise associated with any signal across a
      wide range of masses. In the field, we deployed a PTR-MS at a clean-air coastal
      site and an urban kerbside monitoring station to demonstrate the measurement of
      atmospheric dimethyl sulfide and benzene concentrations, respectively. At both
      sites, we were able to monitor diurnal variations in concentrations at
      unprecedented temporal resolutions (<5 min between successive measurements). We
      then demonstrate how the noise statistic can be applied to enable real
      fluctuations in atmospheric VOC concentrations to be reliably distinguished from
      instrument noise. We conclude by demonstrating how PTR-MS can be used to measure
      real-time VOC emission rate changes from vegetation in response to external
      forcing by examining the effect varying photon-flux density has upon emissions of
      isoprene from a Sitka spruce tree.

PMID- 11999067
TI  - Volatile metal species in coal combustion flue gas.
AB  - Metals are released in effluents of most of combustion processes and are under
      intensive regulations. To improve our knowledge of combustion process and their
      resulting emission of metal to the atmosphere, we have developed an approach
      allowing usto distinguish between gaseous and particulate state of the elements
      emitted. This study was conducted on the emission of volatile metallic species
      emitted from a coal combustion plant where low/medium volatile coal (high-grade
      ash) was burnt. The occurrence of volatile metal species emission was
      investigated by cryofocusing sampling procedure and detection using low
      temperature packed-column gas chromatography coupled with inductively coupled
      plasma-mass spectrometry as multielement detector (LT-GC/ICP-MS). Samples were
      collected in the stack through the routine heated sampling line of the plant
      downstream from the electrostatic precipitator. The gaseous samples were trapped
      with a cryogenic device and analyzed by LT-GC/ICP-MS. During the combustion
      process, seven volatile metal species were detected: three for Se, one for Sn,
      two for Hg, and one for Cu. Thermodynamic calculations and experimental metal
      species spiking experiments suggest that the following volatile metal species are
      present in the flue gas during the combustion process: COSe, CSSe, CSe2, SeCl2,
      Hg0, HgCl2, CuO-CuSO4 or CuSO4 x H2O, and SnO2 or SnCl2. The quantification of
      volatile species was compared to results traditionally obtained by standardized
      impinger-based sampling and analysis techniques recommended for flue gas
      combustion characterization. Results showed that concentrations obtained with the
      standard impinger approach are at least 10 times higher than obtained with
      cryogenic sampling, suggesting the trapping microaerosols in the traditional
      methods. Total metal concentrations in particles are also reported and discussed.

PMID- 11999068
TI  - Detecting endocrine-disrupting compounds by fast impedance measurements.
AB  - The increasing concern worldwide over the adverse effects of endocrine disruptors
      on human health has created a need for screening systems to detect xenoestrogens,
      a diverse group of environmental chemicals that mimic estrogenic actions and are
      hypothesized to decrease male fertility. Here, we describe a novel, class
      selective detector that uses fast impedance measurements to monitor the binding
      of estrogen and xenoestrogens to a native estrogen receptor. We embedded the
      receptor in synthetic lipid bilayers attached to gold electrodes. The lipid
      bilayers serve as electrical circuits constructed of resistors and capacitors.
      Estrogen binding to the receptor-modified electrode is immediately followed by
      conformational changes in the lipid layer, leading to alterations of the
      electrical circuit components that are detected by fast impedance measurements.
      The electrochemical system enabled characterization of changes in the bilayer
      structure and quantification of estrogen binding to the receptor. To assess the
      effectiveness of the method for detecting environmental estrogenic chemicals, we
      chose two classes of xenoestrogens: bisphenol A, a synthetic xenoestrogen, and
      genistein, a phytoestrogen. This system is highly sensitive and amenable to use
      in the field, providing an efficient and economic tool for measuring minuscule
      amounts of endocrine-disrupting chemicals in environmental or human samples.

PMID- 11999069
TI  - Root turnover: an important source of microbial substrates in rhizosphere
      remediation of recalcitrant contaminants.
AB  - The growth dynamics and phenolic content of mulberry (Morus sp.) fine roots (<1
      mm diameter) were determined and examined in relationship to rhizosphere
      remediation of recalcitrant soil contaminants. Root turnover measurements of
      rhizotron-grown plants showed that 58% of the fine roots produced during a 6
      month growing season (June-November) died at the end of the season. The
      concentration of phenolic compounds in fine roots increased approximately 2-fold
      during the later stages of the season, and the total phenolic content of dead
      fine roots reached a maximum value of 38 mg/g dry weight. The late-season
      increase in total phenolics was primarily due to accumulation of three different
      flavones (morusin, morusinol, and kuwanon C). These three flavones were shown to
      support the growth of the bacterium Burkholderia sp. LB400, a degrader of
      polychlorinated biphenyls (PCBs). Thus, it has been established that, upon death,
      the fine roots of mulberry can serve as a source of substrate for PCB-degrading
      bacteria. These results establish for the first time that the chemical content
      and turnover rate of fine roots should be considered an important aspect of
      rhizosphere remediation.

PMID- 11999070
TI  - Fractional factorial design to investigate the influence of heavy metals and
      anions on acid neutralization behavior of cement-based products.
AB  - A major concern of cement-based solidification/stabilization of hazardous wastes
      is the interaction of waste contaminants on cement properties. Literature
      contains many examples of studies on the interference of individual contaminants
      on cement properties. Conversely, little information is available on how the
      interactions between contaminants affectthe properties of cement/waste systems.
      This paper provides a discussion on the interference mechanisms exerted by seven
      contaminants, five heavy metals and two anions, on cement hydration. The seven
      contaminants were selected on the basis of the typical composition of municipal
      solid waste incineration (MSWI) fly ash. Spiking experiments using pure compounds
      were performed according to a 2IV(7-3) fractional factorial design to simulate
      addition of MSWI fly ash to ordinary Portland cement. The acid neutralization
      behavior of the laboratory cement-contaminant mixtures was studied to detect the
      presence of solid phases responsible for the buffering capacity of the solid
      matrix. The results from the experimental work showed that Zn, Cl-, and SO4(2-)
      were the major factors influencing, occasionally in combination with other
      contaminants, strength and acid neutralization capacity of the cementitious
      products. The release of Cd, Cr, Cu, and Pb in the eluates as a function of pH
      also suggested possible chemical immobilization mechanisms of such metals within
      the hardened matrix.

PMID- 11999071
TI  - Diffusive partitioning tracer test for nonaqueous phase liquid (NAPL) detection
      in the vadose zone.
AB  - This paper proposes the theory and practical application of a new partitioning
      tracer test for nonaqueous phase liquid (NAPL) detection in the vadose zone,
      which is based on diffusion. A mixture of chlorofluorocarbons as gaseous tracers
      is injected into the vadose zone to form a point source at the injection point.
      While the tracers diffuse away, small volumes of gas are withdrawn from the
      injection point. The quantitative determination of the NAPL saturation is based
      on a comparison of the concentration decline of tracers with different air-NAPL
      partitioning coefficients. The test has been evaluated in laboratory sand columns
      contaminated with dodecane. NAPL in saturations of 0.8-4% of the total porosity
      have been quantified in a wide range of different water contents. Actual and
      measured NAPL saturations calculated as an average from four different tracer
      pairs agreed within +/-30%. The new method was successfully used for repeated
      NAPL quantification in a large-scale field lysimeter contaminated with artificial
      kerosene. This rapid and inexpensive test is potentially of value for site
      investigations especially in combination with soil gas measurements, because it
      requires similar equipment. Possible applications are source delineation and
      repeated NAPL quantification in situ during a remediation.

PMID- 11999072
TI  - Development of new vanadium-based oxide catalysts for decomposition of
      chlorinated aromatic pollutants.
AB  - Supported transition metal oxides and vanadium-containing multi-metallic oxides
      were investigated to develop new catalysts for the catalytic destruction of
      highly toxic polychlorinated aromatic pollutants such as polychlorinated
      benzenes, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs),
      and/or biphenyls (PCBs) from waste gases. The decomposition of 1,2
      dichlorobenzene (Cl2Bz) was chosen as a model reaction. Titania-supported
      vanadium catalyst (VOx/TiO2) showed the highest activity and stability among the
      binary oxides tested even in the presence of water vapor. The optimum loading of
      vanadia was 5 wt %, corresponding to half a monolayer, suggesting that the active
      species are tetrahedral vanadyl species on titania. Characterizations of the
      VOx/TiO2 catalysts were carried out with XRD, laser Raman spectroscopy, and TPR.
      Multi-metallic VOx/TiO2 catalysts prepared by incorporating Mo, W, or Cr showed
      enhanced activities for Cl2Bz oxidation. Among the tested catalysts, V-Mo-Ox/TiO2
      catalysts wash-coated on the cordierite honeycomb showed a good activity for the
      decomposition of the toxic PCDDs/PCDFs in the flue gas emitted from a municipal
      solid waste incinerator (MSWI).

PMID- 11999073
TI  - Binding and desulfurization characteristics of pulp black liquor in
      biocoalbriquettes.
AB  - To control pollutant emissions from coal combustion in some developing countries,
      biocoalbriquette, an artificially produced solid fuel, was developed. Both the
      breaking strength and production costs of the biocoalbriquette have become
      essentially the most important factors in popularizing it in these countries. To
      increase the breaking strength and decrease the production costs, it is proposed
      in this study to use pulp black liquor, a byproduct from the pulp production
      industry, as a binder. The influences of pulp black liquor on the briquetting and
      combustion characteristics were investigated. Furthermore, the desulfurization
      characteristics of pulp black liquor were also evaluated through combustion
      experiments. The study results show that the briquetting pressure has a limited
      effect on the breaking strength. An increase in the briquetting pressure yields
      greater breaking strength of up to the 50 MPa. Above 50 MPa, the breaking
      strength changes very little with the briquetting pressure. The use of pulp black
      liquor has had a greater effect on increasing the breaking strength than on
      changing the briquetting pressure and also on improving the combustion
      characteristics of the biocoalbriquette. On the other hand, pulp black liquor has
      some desulfurization capabilities. When used as a binder, it not only increases
      the breaking strength and decreases the necessary briquetting pressure, but it
      also improves some characteristics of the combustion and reduces the pollutants
      emission.

PMID- 11999074
TI  - FTIR investigation of adsorption and chemical decomposition of CCl4 by high
      surface-area aluminum oxide.
AB  - Chlorinated hydrocarbons are among the most recalcitrant pollutants for control
      by sorption or catalytic destruction. High surface-area alumina holds promise as
      a catalytic media as well as a component of other binary catalyst systems. We
      have prepared an alumina catalyst using the aerogel technique that has a very
      high surface area of 550 m2/g. This catalyst destroys carbon tetrachloride with
      an efficiency >99% at 400 degrees C. Its reactivity toward carbon tetrachloride
      is remarkably higher than that of commercial alumina, which has a surface area of
      155 m2/g. Carbon dioxide is the major product. Minor products include hydrogen
      chloride and tetrachloroethylene along with traces of phosgene. Some of the
      carbon tetrachloride reacts with the alumina to form aluminum chloride, which
      vaporizes to reveal a fresh catalytic surface. A mechanism for adsorption and
      destruction has been developed that involves chemisorption followed by surface to
      adsorbate oxygen transfer and adsorbate to surface chlorine transfer.

PMID- 11999075
TI  - Studies on the mechanisms of lead immobilization by hydroxyapatite.
AB  - The sorption of lead by synthetic hydroxyapatite (HA) from solutions containing
      Pb2+ initial concentrations up to 1770 mg L(-1) was studied. X-ray diffractometry
      (XRD) associated with Rietveld methodology for refining the spectra pattern was
      used in order to characterize the mechanisms of lead uptake. It is shown that the
      dissolution of hydroxyapatite is followed by the formation of a solid solution,
      Pb(10-x)Ca(x)(PO4)6(OH)2, with Pb ions mostly occupying Ca(II) sites. The Ca/Pb
      molar ratio of this solid solution decreases continuously until it reaches the
      structure of a pure hydroxypyromorphite. The cell parameters and the crystallite
      mean size behavior of both mineral phases reinforce the hypothesis that
      hydroxypyromorphite, PbHA, formation is the end of a process in which Pb(10
      x)Ca(x)(PO4)6(OH)2 crystallites are continuously dissolved and recrystallized
      producing crystals with lower calcium content. Combination of Inductively Coupled
      Plasma spectrometry (ICP), chemical analysis, and XRD results permitted the
      conclusion that lead ions are not completely immobilized by precipitating Pb(10
      x)Ca(x)(PO4)6(OH)2. Additional surface mechanisms also contribute to Pb2+ uptake.
      During Pb2+ sorption process, pH variations of the solution phase showed a more
      complex pattern than previously reported. Contribution of surface mechanisms, in
      addition to the hydroxyapatite dissolution, could explain this behavior.

PMID- 11999076
TI  - Cadmium uptake by hydroxyapatite synthesized in different conditions and
      submitted to thermal treatment.
AB  - This paper intends to evaluate the uptake of cadmium ions from aqueous solution
      by 21 hydroxyapatite samples which have been synthesized in different conditions.
      It has been determined thatthe variation on the hydroxyapatite sorption capacity
      is neither related to sample solubility nor to hydroxyapatite Ca/P molar ratio.
      Cd2+ sorption is controlled by sample BET surface area, which shows a direct
      dependence on the hydroxyapatite crystallite dimensions. The hydroxyapatite pore
      distribution presented modes at 1000 and 60,000 A, corresponding to
      intracrystallite voids and voids between the agglomerate of these crystallites,
      respectively. Pores belonging to the former mode immobilize the major part of
      Cd2+. The influence of sample thermal treatment on Cd2+ sorption efficiency has
      been studied using hydroxyapatite samples calcined at temperatures ranging from
      500 to 1140 degrees C. Similarly to nonthermally treat samples, the Cd2+ sorption
      on calcined hydroxyapatite could be described by Langmuir isotherms. The results
      showed that the maximum sorption capacity decreased from 0.631 mmol g(-1) for the
      noncalcined sample to 0.150 mmol g(-1) for the one calcined at 900 degrees C.
      This drop in the sorption capacity could also be explained by a reduction in its
      specific surface area, which is induced bythe increase of the crystal size.

PMID- 11999077
TI  - Advanced mercury removal from gold leachate solutions prior to gold and silver
      extraction: a field study from an active gold mine in Peru.
AB  - Mercury contamination in the Gold-Cyanide Process (GCP) is a serious health and
      environmental problem. Following the heap leaching of gold and silver ores with
      NaCN solutions, portions of the mercury-cyano complexes often adhere to the
      activated carbon (AC) used to extract the gold. During the electrowinning and
      retorting steps, mercury can be (and often is) emitted to the air as a vapor.
      This poses a severe health hazard to plant workers and the local environment.
      Additional concerns relate to the safety of workers when handling the mercury
      laden AC. Currently, mercury treatment from the heap leach solution is
      nonexistent. This is due to the fact that chelating ligands which can effectively
      work under the adverse pH conditions (as present in the heap leachate solutions)
      do not exist. In an effort to economically and effectively treat the leachate
      solution prior to passing over the AC, a dipotassium salt of 1,3
      benzenediamidoethanethiol (BDET2-) has been developed to irreversibly bind and
      precipitate the mercury. The ligand has proven to be highly effective by
      selectively reducing mercury levels from average initial concentrations of 34.5
      ppm (parts per million) to 0.014 ppm within 10 min and to 0.008 ppm within 15
      min. X-ray powder diffraction (XRD), proton nuclear magnetic resonance (1H NMR),
      Raman, and infrared (IR) spectroscopy demonstrate the formation of a mercury
      ligand compound, which remains insoluble over pH ranges of 0.0-14.0. Leachate
      samples from an active gold mine in Peru have been analyzed using cold vapor
      atomic fluorescence (CVAF) and inductively coupled plasma optical emission
      spectroscopy (ICP-OES) for metal concentrations before and after treatment with
      the BDET2- ligand.

PMID- 11999078
TI  - Integrated decision support system for waste minimization analysis in chemical
      processes.
AB  - The need to build and operate environmentally friendly plants has challenged the
      chemical industry to consider waste minimization or even elimination starting
      from the early stages of process development. A thorough waste minimization
      analysis requires specialized expertise and is laborious, time-consuming,
      expensive, and knowledge-intensive. This has caused a major technical barrier for
      implementing waste minimization programswithin the industry. Previously, we had
      reported a systematic methodology and a knowledge-based system, called
      ENVOPExpert, for identifying waste minimization opportunities in chemical
      processes. In this paper, we propose an integrated qualitative-quantitative
      methodology to identify waste minimization alternatives and assess their efficacy
      in terms of environmental impact and process economics. A qualitative analysis is
      first conducted to identify the sources of wastes and to propose alternatives for
      eliminating or minimizing them. Environmental impact of each alternative is then
      calculated by doing a quantitative pollutant balance. The capital expenditure
      required for implementing the alternative and the resulting plant operating costs
      are also calculated and used in the evaluation of the waste minimization
      alternatives. Through this, practical and cost-effective options can be
      identified. This methodology has been implemented as an integrated decision
      support system and tested using the hydrodealkylation process case study with
      satisfactory results.

PMID- 11999079
TI  - Prevalence of coronary artery disease in India.

PMID- 11999080
TI  - Burden of rheumatic and congenital heart disease in India: lowest estimate based
      on the 2001 census.

PMID- 11999081
TI  - Coronary arterial fistula to the right atrium.

PMID- 11999082
TI  - Lipoprotein (a) and lipid levels in young patients with myocardial infarction and
      their first-degree relatives.

PMID- 11999083
TI  - Final report on tobacco risks from a case-control study.

PMID- 11999084
TI  - Hormone replacement therapy and coronary artery disease: buried alive?

PMID- 11999085
TI  - Management of asymptomatic valvular aortic stenosis.

PMID- 11999086
TI  - Predictive accuracy of commissural morphology and its role in determining the
      outcome following Inoue balloon mitral valvotomy.
AB  - BACKGROUND: Commissural morphology is an important predictor of outcome following
      balloon mitral valvotomy. The aim of this prospective study was to assess if the
      site of commissural splitting could be reliably predicted by echocardiography and
      whether the extent of commissural split affected the result of balloon mitral
      valvotomy. METHODS AND RESULTS: A total of 140 patients (mean age 29.1+/-8.6
      years) were studied. Prediction of splitting was done based on the presence of
      echolucent dark zones as seen in the parasternal short-axis view on
      echocardiography. Of 102 patients in whom a split of both commissures was
      predicted, the prediction was accurate in 86% (88/102). Of 33 patients with a
      predicted unilateral split, the accuracy of prediction was 82% (27/33). In the 5
      patients with bilateral commissural fibrosis (in whom none of the commissures
      were predicted to split), all had a unilateral split. Overall, 93 patients (66%)
      had a bilateral commissural split, 43 (31%) had a unilateral split, and 4 had no
      commissural split. All the latter 4 developed moderate-to-severe mitral
      regurgitation. Those with bilateral commissural split following balloon mitral
      valvotomy had lower transmitral gradients (5.53+/-1.46 v 7.4+/-1.2 3 mmHg, p =
      0.03) and greater mitral valve area (1.83+/-0.15 v. 1.64+/-0.15 cm2, p<0.02), as
      compared to those with unicommissural split. The incidence of an increase in
      mitral regurgitation by > or = grade 1 was also lower in the former group (7.5%
      v. 28%). An optimal result with the first dilatation (using a balloon size <2 mm
      of the predicted size) was achieved more frequently in those with a bilateral
      split (18% vs 8%). Oversizing of the balloon by 2 mm (of the predicted size) was
      done more frequently (19% v. 7%) in those with unicommissural split. CONCLUSIONS:
      We conclude that the assessment of commissural morphology is possible with
      excellent predictive accuracy. In this study, those with bilateral commissural
      split had more favorable hemodynamic results with lower transmitral gradients.
      greater mitral valve area and lesser frequency of mitral regurgitation in
      contrast to those with unicommissural split.

PMID- 11999087
TI  - Chlamydia pneumoniae infection and nonspecific aortoarteritis: search for a link
      with a nonatherosclerotic inflammatory arterial disease.
AB  - BACKGROUND: The association between Chlamydia pneumoniae infection and
      atherosclerosis has gained recognition. However, the nature of this association
      is controversial. The infective link may not be specific for atherosclerosis and
      may also exist in other nonatherosclerotic arterial diseases. We investigated
      patients with nonspecific aortoarteritis for serological evidence of prior
      Chlamydia pneumoniae infection. METHODS AND RESULTS: Fifty patients each of
      nonspecific aortoarteritis and coronary artery disease with angiographic evidence
      of significant (>70%) coronary artery lesions were tested for the presence of IgG
      antibodies against Chlamydia pneumoniae by micro-immunofluorescence assay and
      compared with 50 age- and sex-matched normal healthy controls. The number of
      patients with nonspecific aortoarteritis who tested positive for Chlamydia
      pneumoniae antibodies (IgG) was not significantly different from controls (8 v.
      7, p=ns). The mean titer amongst positive subjects in the two groups was also
      similar (1:40+/-40 v. 1:50+/-25; p=ns). Patients with coronary artery disease
      were significantly older than patients with nonspecific aortoarteritis and
      controls (53.2+/-5.8 v. 21.2+/-9.9 years and 24.5+/-5.2 years, p<0.01 for both)
      and showed a higher seroprevalence of prior Chlamydia pneumoniae infection (18 v.
      8 and 7, p < 0.05 for both). The mean IgG titers of patients with coronary artery
      disease who tested positive were also significantly higher than the other two
      groups (1:98+/-34 v. 1:40+/-40, p<0.001 and 1:98+/-34 v. 1:50+/-25, p<0.01,
      respectively). CONCLUSIONS: In patients with nonspecific aortoarteritis, the
      seroprevalence of prior Chlamydia pneumnoniae infection is not more than that in
      healthy individuals of the same age group, but is significantly lesser than that
      in patients with coronary artery disease. Thus Chlamydia pneumoniae infection may
      not be associated with all forms of chronic inflammatory arterial lesions.

PMID- 11999088
TI  - Lipoprotein (a) phenotypes in south Indian patients with coronary artery disease.
AB  - BACKGROUND: Plasma lipoprotein (a) levels in the Indian population are varied;
      this study was undertaken to determine the relationship between plasma
      lipoprotein (a) levels and their phenotypes in a group of south Indian patients
      with coronary artery disease. METHODS AND RESULTS: A total of 104 patients with
      angiographically proven coronary artery disease were compared with 104 age- and
      sex-matched controls with no risk factors such as hypertension, diabetes and
      smoking. Lipoprotein (a) levels were measured by an in-house ELISA method and its
      phenotyping was done by SDS agarose gel electrophoresis. Plasma lipoprotein (a)
      levels were significantly elevated in patients with coronary artery disease as
      compared to controls (33.4+/-26.1 mg/dl v. 21.4+/-12.8 mg/dl; p<0.01).
      Lipoprotein (a) phenotyping showed that low-molecular weight isoforms were found
      only in 19.2% of the patients with coronary artery disease and their plasma
      lipoprotein (a) levels were significantly elevated compared to coronary artery
      disease patients with higher molecular weight isoforms (50.9+/-34.2 mg/dl v.
      29.24+/-20.06 mg/dl; p<0.001). CONCLUSIONS: Plasma lipoprotein (a) levels are
      significantly elevated in patients with coronary artery disease as compared to
      controls. The commoner phenotype in a South Indian population is the larger
      apolipoprotein (a). in which the lipoprotein (a) levels are lower. Hence the
      contribution of lipoprotein (a) phenotype to the lipoprotein (a) levels in our
      population, if any, is modest.

PMID- 11999089
TI  - A community-based rheumatic fever/rheumatic heart disease cohort: twelve-year
      experience.
AB  - BACKGROUND: A pilot rheumatic fever and rheumatic heart disease control porject
      was started in 1988 in blocks of district Ambala (Haryana) to test the
      feasibility of early detection, treatment and secondary prophylaxis for rheumatic
      fever/rheumatic heart disease cases. School teachers, students and health workers
      were trained to identify and refer suspected cases of rheumatic fever/rheumatic
      heart disease to the community health center where physicians examined the
      suspected cases and monthly secondary prophylaxis was provided to the confirmed
      cases. METHODS AND RESULTS: A survey of registered cases was done in 1999 to
      determine the compliance rate of secondary prophylaxis and to describe clinical
      and epidemiologic features of the registered cohort of rheumatic fever/rheumatic
      heart disease patients. A total of 257 patients had been registered till the end
      of 1999 with 1263 person-years of follow-up. Out of these registered patients,
      132 were receiving secondary prophylaxis, 52 had died, 17 had migrated, 8 were
      lost to follow-up, 18 had stopped prophylaxis and 30 completed the prophylaxis
      course. The mean age at registration was 18 years. Half of the cases were in the
      6-15 years age group at registration. Over half of the patients were registered
      with a history of rheumatic fever. Fever was the most common symptom (75.9%).
      Carditis was more common among cases with recurrent attacks of rheumatic fever
      than after a first attack. The mortality in rheumatic fever/rheumatic heart cases
      was 32.5/1000 person-years. The mean age at death was 24.4 years. Compliance with
      secondary prophylaxis was 92% during the past 12 years. CONCLUSIONS: A rheumatic
      fever/rheumatic heart disease control program can be sustained within the primary
      health care system and the case registry can be utilized not only for monitoring
      the program but also to gain insight into the epidemiology of the disease.

PMID- 11999090
TI  - Prevalence of coronary heart disease and risk factors in an urban Indian
      population: Jaipur Heart Watch-2.
AB  - BACKGROUND: The prevalence of risk factors for coronary heart disease has been
      inadequately studied in India. A repeat cross-sectional survey was carried out to
      evaluate the changes in the major coronary risk factors in the urban population
      of Jaipur previously studied in the early 1990s. METHODS AND RESULTS: Randomly
      selected adults > or =20 years of age were studied using stratified sampling. The
      target study sample was 1800 with a population proportionate gender distribution
      (males 960, females 840). Coronary risk factors, anthropometric variables, blood
      pressure, ECG, fasting blood glucose and lipids were evaluated. A total of 1123
      subjects (62.4%) (males 550, females 573) were examined. Fasting blood samples
      were available in 523 males and 559 females. Overall coronary heart diesase
      prevalence, diagnosed by history or ECG changes, was found in 34 males (6.18%)
      and 58 females (10.12%). Risk factor prevalence showed that smoking/tobacco use
      was present in 201 males (36.5%) and 67 females (11.7%). Physical inactivity,
      either work-related or leisure time, was seen in 157 males (28.5%) and 130
      females (22.7%). Hypertension (> or =140 and/or 90 mmHg) was present in 200 males
      (36.4%) and 215 females (37.5%). Diabetes diagnosed by history or fasting glucose
      > or =126 mg/dl was found in 72 males (13.1%) and 65 females (11.3%). Obesity,
      body mass index > or =27 kg/m2 was present in 135 males (24.5%) and 173 females
      (30.2%), while truncal obesity (waist:hip >0.9 males, >0.8 females) was found in
      316 males (57.4%) and 392 females (68.4%). The most common dyslipidemia in both
      males and females was low HDL-cholesterol (<40 mg/dl: males 54.9%, females
      54.2%). High total cholesterol levels of > or =200 mg/dl (males 37.4%, females
      4.1%), high LDL-cholesterol levels of > or =130 mg/dl (males 37.0%, females
      45.8%) and high levels of triglycerides > or = 150 mg/dl (males 32.3%, females
      28.6%) were also seen in a significant number. Hypertension, obesity, truncal
      obesity, diabetes and dyslipidemias increased significantly with age in both
      males and females (Mantel-Haenzel chi2 for trend, p<0.05). CONCLUSIONS: There is
      a high prevalence of standard coronary risk factors--smoking, physical
      inactivity, hypertension, hypercholesterolemia, diabetes and obesity--as well as
      factors peculiar to south Asians--truncal obesity, low HDL-cholesterol and high
      triglycerides--in this urban Indian population. As compared to a previous study
      in the early 1900s in a similar population, there is a significant increase in
      the number of people with obesity, diabetes and dyslipidemias.

PMID- 11999091
TI  - Ventricular septal defect with congenital mitral valve disease: long-term results
      of corrective surgery.
AB  - BACKGROUND: A retrospective analysis of the mortality, morbidity and long-term
      follow-up of patients undergoing corrective surgery for ventricular septal defect
      and congenital mitral valve disease is presented. METHODS AND RESULTS: Between
      January 1991 and December 2000, 69 consecutive patients aged 2 months to 45 years
      (median 18 months) underwent repair of ventricular septal defect and associated
      mitral valve disease. In 52 patients (75%), the ventricular septal defects were
      located in the perimembranous and subarterial area. Forty-six patients had
      congenital mitral incompetence and 23 had congenital mitral stenosis. The
      ventricular septal defect was repaired through the right atrium in all. Sixty
      five patients underwent reconstruction of the mitral valve and 4 underwent
      primary mitral valve replacement. Another 4 patients underwent mitral valve
      replacement after a failed repair. Associated procedures included: patent ductus
      arteriosus ligation (n=12), aortic valve replacement (n=6), coarctation repair
      (n=13), interrupted aortic arch repair (n=1), atrial septal defect closure (n=17)
      and Takeuchi repair (n=1). There were 6 early deaths (8.6%). Three deaths were
      due to pulmonary arterial hypertensive crisis and one due to residual mitral
      stenosis. One death was due to intractable congestive heart failure. Another
      patient died due to persistent low cardiac output. Follow-up ranged from 6 months
      to 120 months (mean 64.4+/-33.6 months). Reoperation was required in 22 patients,
      mainly for recurrent/residual mitral valve dysfunction or hemodynamically
      significant left ventricular outflow tract obstruction. There were 4 late deaths,
      2 due to residual mitral stenosis and the other 2 as a result of a thrombosed
      prosthetic valve. At 10 years, the actuarial survival rate was 850+/-5.0%, and
      freedom from reoperation was 45%+/-10.0%. CONCLUSIONS: Reconstruction of the
      mitral valve along with closure of VSD is possible in most cases. However,
      careful follow-up is recommended to detect changes in the mitral valve status
      over a course of time.

PMID- 11999092
TI  - Left main coronary artery compression by dilated main pulmonary artery in
      endocardial cushion defect.
AB  - A 56-year-old man was evaluated for exertional dyspnoea. Chest X-ray showed mild
      cardiomegaly and a dilated main pulmonary artery. On echocardiogram he was found
      to have ostium primum atrial septal defect with moderate tricuspid insufficiency.
      Cardiac catheterization revealed an oximetry step-up of 14% at low right atrium
      with angiogram demonstrating a cleft in the mitral valve, an elongated left
      ventricular outflow tract and ventricular septal defect closed by a septal
      aneurysm. Coronary angiogram revealed ostial compression of the left main
      coronary artery with the rest of the coronary artery anatomy being normal.

PMID- 11999093
TI  - Giant pulmonary artery aneurysm with right ventricular outflow tract obstruction.
AB  - Aneurysm of the main pulmonary artery is rare. Its natural history is not well
      understood and there are no clear guidelines regarding its optimal treatment. We
      present a case of a huge saccular aneurysm of the main pulmonary artery which was
      associated with infundibular and valvular pulmonary stenosis. It was repaired
      using a pericardial patch with concomitant pulmonary valvotomy and infundibular
      resection. Postoperative recovery was uneventful and the patient is doing well.
      Follow-up echocardiogram revealed good repair.

PMID- 11999094
TI  - Slow pathway ablation without femoral access.
AB  - An 80-year-old woman presented with almost daily episodes of tachycardia. She was
      found to have drug refractory atrioventricular nodal re-entry tachycardia. As she
      was found to have bilateral common iliac vein occlusion, radiofrequency ablation
      of the slow pathway was performed via the subclavian vein. This unique experience
      raises technical issues for catheter positioning.

PMID- 11999095
TI  - Tetralogy of Fallot in monozygotic twins.
AB  - A pair of monozygotic twins having tetralogy of Fallot is reported for the first
      time in the Indian literature. This case report will help in further enriching
      the existing data on genetic hypothesis of congenital heart defects.

PMID- 11999096
TI  - 5-fluorouracil-Induced cardiotoxicity.
AB  - Cardiotoxicity due to antineoplastic agents such as doxorubicin, daunorubicin,
      cyclophosphamide, vincristin, vinblastin, cisplatin and busulfan is well known.
      However, 5-fluorouracil-induced cardiotoxicity is yet to be widely recognized by
      cardiologists. We report a patient who developed 5-fluorouracil-induced
      cardiotoxicity syndrome.

PMID- 11999097
TI  - Expression and functional activity of receptor-Ck in mononuclear cells of a
      homozygous hypercholesterolemic family.
AB  - The study was addressed to explore the expression and functional activity of a
      novel cholesterol-specific cell surface receptor-Ck in a typical homozygous
      familial hypercholesterolemic family. Functional activity of receptor-Ck was
      characterized by its ability to downregulate Bcl-2 gene expression through a 47
      kDa factor having an affinity for the sterol-regulatory element in the promoter
      region of this gene. The result of such a study revealed normal expression and
      functional activity of receptor-Ck accompanied by a lack of Apolipoprotein B
      specific low-density lipoprotein receptor gene expression in the mononuclear
      cells derived from these patients. On the basis of these results, it is tempting
      to speculate that receptor-Ck may be involved in the maintenance of cellular
      cholesterol homeostasis observed in homozygous familial hypercholesterolemic
      patients.

PMID- 11999098
TI  - Transient complete heart block complicating acute rheumatic fever.
AB  - First-degree heart block is a common electrocardiographic manifestation of acute
      rheumatic fever and is included in Jones' diagnostic criteria. Other
      electrocardiographic changes such as sinus tachycardia, bundle branch blocks.
      nonspecific ST-T wave changes, atrial and ventricular premature complexes have
      been reported with variable frequency. However, complete heart block is an
      exceptionally rare manifestation of acute rheumatic fever. We report the clinical
      course of a 16-year-old boy with acute rheumatic fever who had prolonged P-R
      interval in the electrocardiogram on admission which subsequently progressed to
      complete heart block. The patient regained normal sinus rhythm within a few
      minutes without any pharmacologic or electrical intervention.

PMID- 11999099
TI  - The potential for vaccine development against rheumatic fever.

PMID- 11999100
TI  - Prevention of heart disease in India in the 21st century: need for a concerted
      effort.

PMID- 11999101
TI  - The narcissistic exoskeleton: the defensive organization of the rage-type
      murderer.
AB  - After outlining the characteristics of rage-type murder, the author reviews
      possible psychodynamic explanations of the predisposing personality and the act
      itself. He argues that more recent contributions, using an object relations
      perspective, best account for the complexity of the internal world of these
      offenders. Using a single case to illustrate observations drawn from his work
      with nine offenders, the author sets out to develop an understanding of the
      defensive organization present in these apparently normal murderers. He isolates
      a defensive system comprising a set of split object relations that correspond
      with a split between internal and external reality, which he calls the
      "narcissistic exoskeleton." Projective and introjective processes that support
      the defensive organization are discussed. It is suggested that such a profile
      typifies a particular kind of stable borderline personality organization.

PMID- 11999102
TI  - Fraught with the utmost danger: the object relations of mothers who kill their
      children.
AB  - The author explores the psychodynamics of maternal filicide from an object
      relations perspective. Among psychotic women, the murder of the child reflects a
      critical interplay among the mother's neurobiology, constitution, developmental
      experiences, and complex internal object world. Two types of personality
      structure are discussed. For the disorganized type, the psychodynamic scenario
      involves attempts to contend with the danger of massive internal breakdown. For
      the organized type, the scenario involves attempts to contend with the danger of
      persecution and annihilation. For these women, physical violence is used because
      of failures in mentalization, and is an enactment of catastrophic internal
      anxieties.

PMID- 11999103
TI  - Mother-daughter relationships and child sexual abuse: a pilot study of 35 dyads.
AB  - In a pilot study, the authors examine features of mothers' relationships to their
      mothers, spouses, and daughters associated with their daughters' male-perpetrated
      child sexual abuse. Fifteen inner-city Latino mothers and daughters (ages 1-9
      years), referred by child protective agencies for highly suspect or confirmed
      child sexual abuse, were compared to 20 matched control dyads. Significantly more
      case mothers than controls reported relational disturbances intergenerationally,
      including hostility toward their daughters. Mother-daughter relationships should
      be thoroughly assessed when evaluating a child for child sexual abuse.

PMID- 11999104
TI  - Meeting of the minds: ego reintegration after traumatic brain injury.
AB  - Many symptoms of brain injury (e.g, difficulties with speech, intellectual
      functions, concentration, flatness or lability, distractibility) bear a close
      resemblance to inhibitions and compromise formations evident in problematic
      intrapsychic development. Disturbances in intrapsychic function can have an
      organic basis, and errors in differential diagnosis can result when therapists do
      not consider intrapsychic and organic damage in combination. Brain-injured
      individuals need others who are comfortable providing auxiliary functions,
      particularly as an aid in managing anxiety. Understanding the operation of
      anxiety after brain injury can further the capacity of these individuals to
      attain and maintain more gratifying interpersonal relationships.

PMID- 11999105
TI  - Elevated carnitine accumulation by Listeria monocytogenes impaired in glycine
      betaine transport is insufficient to restore wild-type cryotolerance in milk
      whey.
AB  - Listeria monocytogenes accumulates low molecular weight compounds (osmolytes, or
      compatible solutes) in response to chill stress. This response has been shown to
      be responsible, in part, for the chill tolerance of the species. Among the
      osmolytes tested to date, glycine betaine, gamma-butyrobetaine and carnitine
      display the strongest cryoprotective effect. These osmolytes are not synthesized
      in the cell and must be transported from the medium. In this study, the
      compatible solute accumulation profile of the food-borne pathogen L.
      monocytogenes was determined in balanced growth and stationary phase cultures
      grown in milk whey at 7 and 30 degrees C. In balanced growth cultures at 7
      degrees C, glycine betaine (720 nmol/10(10) cfu) and carnitine (130 nmol/10(10)
      cfu) were the major osmolytes accumulated by wild-type L. monocytogenes 10403S,
      whereas carnitine (490 nmol/10(10) cfu) was the dominant osmolyte and glycine
      betaine was present in smaller amounts (270 nmol/10(10) cfu) in a mutant (L.
      monocytogenes LTG59) blocked in the major glycine betaine uptake system, glycine
      betaine porter II. In strain 10403S, glycine betaine and carnitine were present
      in eightfold and twofold excess at 7 degrees C compared to 30 degrees C; the
      respective ratios for strain LTG59 were 6 and 8. The intracellular concentration
      of osmolytes in stationary phase cultures at 7 degrees C was markedly reduced
      compared to that during balanced growth. Furthermore, at 4 degrees C, small but
      highly significant differences in growth were observed between strains. Strain
      LTG59 grew with a lag phase that was significantly longer, a generation time that
      was significantly greater and reached a final cell yield that was significantly
      lower than that of strain 10403S. The elevated accumulation of carnitine in the
      absence of glycine betaine porter II was insufficient to confer the magnitude of
      the cryoprotective effect displayed by the wild type.

PMID- 11999106
TI  - Detection of hepatitis A virus in mussels from different sources marketed in
      Puglia region (South Italy).
AB  - Hepatitis A virus (HAV) infection is endemic in Puglia (South Italy).
      Epidemiological studies indicate that shellfish consumption, particularly
      mussels, is a major risk factor for HAV infection, since these products are eaten
      raw or slightly cooked. Nested reverse transcriptase-polymerase chain reaction
      (RT-PCR) has been shown to be a sensitive technique for the detection of HAV in
      mussels. The aim of the present study was to detect the presence of HAV in a
      large sample of mussels by nested RT-PCR and to confirm the presence of
      infectious viral particles in positive samples by cell culture infection and RT
      PCR confirmation. Two hundred and ninety samples of mussels from different
      sources were collected between December 1999 and January 2000. One hundred
      samples were collected before being subjected to depuration, 90 after depuration,
      and 100 were sampled in different seafood markets. HAV-RNA was detected in 20
      (20.0%) of non-depurated mussels, in 10 (11.1%) of depurated samples, and in 23
      (23.0%) of samples collected in the shellfish markets, without any significant
      difference in the prevalence of positive samples by collection sources (chi2 =
      4.79, p = 0.09). Of the 53 samples found positive by nested RT-PCR, 18 (34.0%)
      resulted positive by cell culture assay. No relationship between viral
      contamination and bacterial contamination was found (p = 0.41). This study
      confirms the usefulness of molecular techniques in detecting HAV in shellfish
      and, thus, for the screening of a large sample of naturally contaminated mussels.
      Improved shellfish depuration methods are needed to obtain virus-safe shellfish
      and reduce the risk for public human health.

PMID- 11999107
TI  - Microbiological activity in stored olive oil.
AB  - The disappearance of the bitter taste of newly produced olive oil during storage
      is due to the enzymatic hydrolysis of the bitter-tasting secoiridoid compound
      known as oleuropein. Current knowledge attributes the enzymatic hydrolysis of the
      oleuropein to the beta-glucosidase present in the olives. The present study,
      however, has demonstrated for the first time that oleuropein present in olive oil
      can be hydrolysed by beta-glucosidase from the yeasts Saccharomyces cerevisiae
      and Candida wickerhamii. The enzymatic analyses carried out directly on the
      untreated olive oil and on sterilized olive oil inoculated with the above
      mentioned yeasts proved the beta-glucosidase activity through the hydrolysis of
      both the synthetic substrate p-nitrophenyl-beta-D-glucopyranoside (PNPG) and the
      oleuropein. The absence of lipases in the isolated S. cerevisiae and C.
      wickerhamii examined lead us to believe that the yeasts contribute in a positive
      way towards the improvement of the organological quality of the oil without
      altering the composition of the triglycerides.

PMID- 11999108
TI  - Microbiological analysis of seed sprouts in Norway.
AB  - As part of larger survey of microbial contamination of fruits and vegetables in
      Norway, four different sprouted seed products were analysed for bacterial and
      parasitic contaminants (n = 300 for bacterial analyses and n = from 17 to 171 for
      parasite analyses, depending on parasite). Escherichia coli O157, Salmonella,
      Listeria monocytogenes, Cyclospora oocysts, Ascaris eggs and other helminth
      parasites were not detected in any of the sprout samples. Thermotolerant coliform
      bacteria (TCB) were isolated from approximately 25% of the sprout samples, with
      the highest percentage of TCB positive samples in alfalfa sprouts. Most TCB were
      Enterobacter spp. and Klebsiella. E. coli was isolated from 8 of 62 TCB positive
      mung bean sprout samples. Cryptosporidium oocysts were detected in 8% of the
      sprout samples and Giardia cysts were detected in 2% of the samples. All the
      Cryptosporidium positive samples, and most of the Giardia positive samples, were
      mung bean sprouts. Parasite concentrations in positive samples were low (between
      1 and 3 oocysts/cysts per 50 g sprouts). Sprout irrigation water was also
      analysed for microbial contaminants. E. coli O157 and L. monocytogenes were not
      detected. TCB were isolated from approximately 40% of the water samples.
      Salmonella reading was isolated from three samples of spent irrigation water on 3
      consecutive days. Cryptosporidium and Giardia were also isolated from spent
      irrigation water. Additionally, eight samples of unsprouted mung bean seed were
      analysed for Cryptosporidium oocysts and Giardia cysts. One or both of these
      parasites were detected in six of the unsprouted seed samples at concentrations
      of between 1 and 5 oocysts/cysts per 100 g unsprouted seed. Whilst our results
      support spent irrigation water as the most suitable matrix for testing for
      bacteria, unsprouted seed is considered the more useful matrix for analysing for
      parasite contaminants.

PMID- 11999109
TI  - Variation among Escherichia coli O157:H7 strains relative to their growth,
      survival, thermal inactivation, and toxin production in broth.
AB  - To estimate the potential outcomes of food processing on the fate of foodborne
      pathogens. variations in microbial parameters such as growth rate, survival time,
      thermal inactivation time, and toxin production must be known. Previous microbial
      studies using single strains or cocktails provide error estimates for the
      uncertainty of the experimental and statistical procedures, but not for
      variations among strains. In this study, the behavior of 17 strains of
      Escherichia coli O157:H7 were followed when placed in synthetic media that
      permitted growth, survival, or thermal inactivation. The parameter values were
      not rejected as being normal, lognormal, gamma, or Weibull distributions. The
      ratio of the standard deviation to mean (normal distribution) for the exponential
      growth rate was 0.16 and for the lag phase duration, it was 0.38. The ratios of
      times to achieve a 4-log10 reduction at two survival conditions were 0.39 and
      0.46; ratios of thermal D values at 55 and 60 degrees C were 0.42 and 0.33,
      respectively. The ratio of the negative log10 of toxin production was 0.24. These
      distributions are larger than the coefficient of variations observed for
      experimental errors in single strain and cocktail experiments. This indicates the
      limitations in precision that predictions of future population numbers can have
      when the potential presence of all strains needs to be considered. This variation
      among strains is applicable whether predictions are made by traditional
      subjective and point estimates or by using models and risk assessments.

PMID- 11999110
TI  - A collaborative study to validate novel field immunoassay kits for rapid
      mycotoxin detection.
AB  - Kits designed to detect ochratoxin A (OA) and T-2 toxin by a membrane-based flow
      through enzyme immunoassay were studied collaboratively by screening cereals
      (wheat, rye, maize and barley) for the presence of these mycotoxins. Sample
      preparation and test procedure were clearly described in the instruction leaflets
      included in the kits. A simple methanol-based extraction followed by filtration
      and dilution steps was prescribed. Reagents were successively pipetted to the
      membrane of the device, then colour development was evaluated visually. Limits of
      detection for the ochratoxin A and T-2 toxin tests were 4 and 50 microg kg(-1),
      respectively. Five laboratories took part in the first stage of this study, and
      five more joined the second stage. Cereal samples (blank, spiked or inoculated)
      were shipped with the kits to the participating laboratories, while results
      obtained were confirmed by high-performance liquid chromatography with
      fluorescence detection and by gas chromatography-mass spectrometry for ochratoxin
      A and T-2 toxin, respectively. Some initial difficulties were encountered. In the
      second stage, four ochratoxin A and four T-2 toxin kits were used by 10
      collaborators to analyse 21 cereal samples. For the ochratoxin A kits, the
      percentage of false positive and false negative results were 2% and 4%,
      respectively. The results of one T-2 toxin kit were outliers and when excluded,
      the overall percentage false positive and false negative results were 6% and 3%,
      respectively.

PMID- 11999111
TI  - Sensitivity analysis for high quantiles of ochratoxin A exposure distribution.
AB  - Using available data from a consumption survey and contamination data on
      ochratoxin A (OA) in food, a sensitivity analysis (SA) for high quantiles (95th
      and 99th quantiles) of OA exposure distribution was carried out, obtained by a
      Monte Carlo simulation in French children. Exposure assessment for food
      contaminants is important to control the risk of foodborne diseases. Risk
      assessors are interested in high quantiles of contaminant exposure distributions.
      As these exposure distributions are generally very asymmetrical, it is difficult
      to obtain relevant and stable high quantiles in such a context. Determining OA
      exposure distribution is complex because it is based on the sum of elementary
      exposure distributions (eight foodstuffs are analysed here), and each one of
      these is the product of a consumption distribution and a contamination
      distribution. The SA enables us to quantify the influences of the parameter
      variability of the consumption and contamination probability density functions
      (pdf) which have been fitted to the data, our simulation model inputs, on the
      95th and 99th quantiles of the output exposure distribution. After some
      preliminary trials, we have postulated a quadratic polynomial regression model
      for the quantiles of OA exposure distribution in view of undertaking this SA.
      This regression model comprises 32 main factors, their 496 two-factor
      interactions and their 32 quadratic terms. The 32 factors are the parameters of
      the fitted pdf: 16 parameters of Gamma distributions relative to the eight
      consumed foods and 16 parameters of Gamma distributions relative to the eight
      food OA contaminations. For an optimal parameter estimation of such a large
      model, we used an experimental design approach depending on a resolution-V
      fractional factorial design of 6561 experiments. The factor ranges are
      established by a preliminary study of bootstrap sampling. From the bootstrap
      samples, the factor ranges are obtained taking into account the correlation
      between the two parameters of the fitted Gamma pdf. A full exposure distribution
      is simulated for each of the 6561 experiments. The consumption dependencies are
      taken into account by the Iman and Conover method. On the basis of this analysis,
      validated and useful models for each desired quantile are obtained showing a
      major influence of the parameters of "Cereals" (consumption and contamination)
      and slightly less so for parameter of "Pork" consumption in the sensitivity of
      the quantiles.

PMID- 11999112
TI  - The microdistribution of oxygen in Danablu cheese measured by a microsensor
      during ripening.
AB  - Profiles of oxygen in Danablu cheese at the age of 1-19 weeks were measured by
      using an oxygen microsensor. In a cheese ripened for 1 week, the percentage
      oxygen saturation decreased to 70% at 0.25-mm depth and further to 50% at 4-mm
      depth. In a more extended determination of oxygen profiles, the spatial and
      temporal development in the oxygen level was investigated at 5-mm resolution at
      the center and 5 mm from the edge of the cylindrical cheeses at a depth of 45 mm.
      Average oxygen saturation decreased from 63% to 0.1% at the centre and from 69%
      to 0.1% at the edge in cheeses from 1 to 19 weeks. In the cheeses ripened for
      more than 3 weeks, oxygen was not detectable, except for a surface layer of 0.25
      mm and in apparent small air pockets within the cheese containing about 3%
      saturated oxygen.

PMID- 11999113
TI  - Enterocin 416K1, an antilisterial bacteriocin produced by Enterococcus
      casseliflavus IM 416K1 isolated from Italian sausages.
AB  - Enterococci (118) from Italian sausages were tested for the production of
      antimicrobial substances. Of these, 7.6% showed antibacterial activity against
      one or several closely related microorganisms used as indicators. Enterococcus
      casseliflavus IM 416K1 in particular produced a bacteriocin (Enterocin 416K1)
      with strong anti-listerial antagonistic activity. The bacteriocin withstood
      heating at 90 degrees C for 120 min and storage at 4 degrees C for 6 months. The
      mode of action was identified as bactericidal. The crude activity of Enterocin
      416K1 was linked to a molecule with an apparent molecular weight smaller than 5
      kDa. Plasmid analysis of E. casseliflavus IM 416K1 revealed the presence of four
      plasmids with different molecular weights (34, 11, 7 and 3.3 MDa). All the Bac-
      variants produced by curing experiments showed loss of the single plasmid of 34
      MDa. Bacteriocin activity and immunity production may be linked to genes located
      on that same plasmid.

PMID- 11999114
TI  - Characterisation of sucrose-negative Yersinia enterocolitica 4/O:3 isolates
      recovered from pig tonsils.
AB  - Sucrose-negative Yersinia enterocolitica isolates of bioserotype 4/O:3 have been
      recovered for the first time. They were found in 2% of the tonsils of clinically
      healthy fattening pigs. These sucrose-negative Y. enterocolitica isolates could
      not be differentiated from Y. kristensenii isolates using API 20E; thus, they
      were identified using PCR and sequencing. Using pulsed-field gel electrophoresis
      (PFGE). NotI profiles of sucrose-negative Y. enterocolitica 4/O:3 isolates showed
      a high similarity to sucrose-positive Y. enterocolitica 4/O:3 isolates. This
      study demonstrated that sucrose-negative Y. enterocolitica 4/O:3 isolates of
      porcine origin can harbour virulence genes; plasmid-encoded virulence markers
      were found in 8 out of 11 isolates and all isolates contained chromosomal-encoded
      virulence markers. Thus, the pathogenicity of sucrose-negative Yersinia isolates
      should always be assessed.

PMID- 11999115
TI  - Protein expression during lag phase and growth initiation in Saccharomyces
      cerevisiae.
AB  - In order to obtain a better understanding of the biochemical events taking place
      in Saccharomyces cerevisiae during the lag phase, the proteins expressed during
      the first hours after inoculation were investigated by two-dimensional (2-D) gel
      electrophoresis and compared to those expressed in late respiratory growth phase.
      The studies were performed on a haploid strain (S288C) grown in defined minimal
      medium. Some of the abundant proteins, whose expression relative to total protein
      expression was induced during the lag phase, were identified by MALDI MS, and the
      expression of the corresponding genes was assessed by Northern blotting. The rate
      of protein synthesis was found to increase strongly during the lag phase and the
      number of spots detected on 2-D gels increased from 502 spots just after
      inoculation to 1533 spots at the end of the lag phase. During the first 20 min,
      the number of detectable spots was considerably reduced compared to the number of
      spots detected from the yeast in respiratory growth just prior to harvest and
      inoculation (747 spots), indicating an immediate pausing or shutdown in synthesis
      of many proteins just after inoculation. In this period, the cells got rid of
      most of their buds. The MALDI MS-identified, lag phase-induced proteins were
      adenosine kinase (Ado1p), whose cellular role is presently uncertain, cytosolic
      acetaldehyde dehydrogenase (Ald6p) and (DL)-glycerol-3-phosphatase 1, both
      involved in carbohydrate metabolism, a ribosomal protein (Asc1p), a fragment of
      the 70-kDa heat shock protein Ssb1, and translationally controlled tumour protein
      homologue (Yk1056cp), all involved in translation, and S-adenosylmethionine
      synthetase I involved in biosynthesis reactions. The level of mRNA of the
      corresponding genes was found to increase strongly after inoculation. By pattern
      matching using previously published 2-D maps of yeast proteins, several other lag
      phase-induced proteins were identified. These were also proteins involved in
      carbohydrate metabolism, translation, and biosynthesis reactions. The identified
      proteins together with other, yet unidentified, lag phase-induced proteins are
      expected to be important for yeast growth initiation and could be valuable
      biological markers for yeast performance. Such markers would be highly beneficial
      in the control and optimisation of industrial fermentations.

PMID- 11999116
TI  - Quantitative risk assessment of human infection from Escherichia coli O157
      associated with recreational use of animal pasture.
AB  - A quantitative microbial risk assessment incorporating Monte Carlo simulations is
      described which estimates the probability of Escherichia coli O157 infection of
      humans by visiting pasture previously grazed by cattle. The risk assessment is
      performed for a number of scenarios including a variation in the grazing period
      prior to the human visit, the duration of visit (8-h day or 24-h camp) and the
      level of E. coli O157 shed by the cattle. Assuming the cattle have been on the
      field for 28 days, followed directly by a human visit, and the proportion of
      animals shedding the organism are as described in previous surveys 5 +/- 1%
      (Synge, B.A., Gunn, G.J., Ternent, H.E., Hopkins, G.F., Thomson-Carter, F.,
      Foster, G., Chase-Topping, M., McKendrick, I., 2001). Prevalence and factors
      affecting the shedding of verocytotoxin producing Escherichia coli O157 in beef
      cattle in Scotland. In: Concerted Action CT98-3935 Veroctotoxigenic E. coli in
      Europe, 5. Epidemiology of Verocytotoxigenic E. coli, Dublin, pp. 98-103.), a
      probability of infection of 0.1% is attained for 8- and 24-h periods when the
      cattle are shedding approximately 10(3) and 10(4) CFU g(-1), respectively. Monte
      Carlo simulations demonstrated that risk mitigation strategies of removing cattle
      from the pasture 4 weeks prior to the human visit in addition to physical removal
      of faeces showed significant reductions in potential infection rates.

PMID- 11999117
TI  - Rapid assessment of cell viability of Lactobacillus delbrueckii subsp. bulgaricus
      by measurement of intracellular pH in individual cells using fluorescence ratio
      imaging microscopy.
AB  - The aim of this study was to investigate if the measurement of intracellular pH
      (pHi) of individual cells by fluorescence ratio imaging microscopy (FRIM) could
      be utilized as a rapid method for determining the bacterial viability, using
      Lactobacillus delbrueckii subsp. bulgaricus as a model organism. Five different
      standardized cultures with equal cell densities but varying viability were
      prepared on a trial-to-trial basis by combining aliquots of frozen and
      lyophilized cells with a 50-fold difference in viability, determined by the
      ability to form colonies on solid growth media. The acidification of milk and
      Acidification Power Test were used to determine the activity of these cultures.
      As expected, the cultures containing a higher proportion of viable cells
      acidified milk faster and performed better in the Acidification Power Test. All
      cells were fluorescent after staining with carboxyfluorescein diacetate
      succinimidyl ester but frozen cells reached higher fluorescence intensities than
      lyophilized cells. The number of strongly fluorescent cells determined by flow
      cytometry exceeded the number of viable cells determined by CFU. Analysis of pHi
      of individual cells by FRIM at an extracellular pH of 6.0 revealed two
      populations of cells with an average pHi of 6.9 +/- 0.1 and 6.1 +/- 0.1. As the
      number of cells maintaining a pH-gradient of 0.9 +/- 0.1 correlated well with
      CFU, we suggest that FRIM can be used as a rapid method for the determination of
      viability of L. delbrueckii subsp. bulgaricus. Measurement of pHi on a single
      cell basis is expected to provide accurate prediction of the fermentation
      performance in a wider range of industrial fermentation.

PMID- 11999118
TI  - Spectral surface plasmon resonance biosensor for detection of staphylococcal
      enterotoxin B in milk.
AB  - This work evaluates a newly developed wavelength modulation-based SPR biosensor
      for the detection of staphylococcal enterotoxin B (SEB) in milk. Two modes of
      operation of the SPR biosensor are described: direct detection of SEB and
      sandwich assay. In the sandwich assay detection mode, secondary antibodies are
      bound to the already captured toxin to amplify sensor response. Samples including
      SEB in buffer and SEB in milk were analyzed in this work. The SPR biosensor has
      been shown to be capable of directly detecting concentrations of SEB in buffer as
      low as 5 ng/ml. In sandwich detection mode, the lowest detection limit was
      determined to be 0.5 ng/ml for both buffer and milk samples. The reported
      wavelength modulation-based SPR sensor provides a generic platform which can be
      tailored for detection of various foodborne pathogens and agents for food
      analysis and testing.

PMID- 11999119
TI  - Sensitivity analysis of Salmonella enteritidis levels in contaminated shell eggs
      using a biphasic growth model.
AB  - Salmonella enteritidis (SE) is a common foodbome pathogen, the transmission of
      which is primarily associated with the consumption of contaminated Grade A shell
      eggs. In order to estimate the level of SE present in raw shell eggs, it is
      necessary to consider the protective effects of the egg albumin, which
      effectively inhibits SE growth in a time- and temperature-dependent manner. In
      this study, a SE growth model was produced by combining two mathematical
      equations that described both the extended lag phase of SE growth (food
      component) and a SE growth model (pathogen component). This biphasic growth model
      was then applied to various egg handling scenarios based on the farm-to-table
      continuum, including in-line and off-line processing facilities with
      consideration of key events in production, processing, transportation, and
      storage. Seasonal effects were also studied. Monte Carlo simulation was used to
      characterize variability in temperature and time parameter values influencing the
      level of SE to which individuals are exposed. The total level of SE consumed was
      estimated under best, most likely, and time-temperature abusive handling
      scenarios. The model estimated that, in most cases, there was no SE growth in
      contaminated eggs handled under most likely practices, because 10-70% of the yolk
      membrane remained intact. Under abusive handling scenarios, complete loss of yolk
      membrane integrity frequently occurred by the time eggs reach the distribution
      phase, followed by subsequent SE growth, which was often quite rapid. In general,
      the effect of season and processing method (in-line vs. off-line) was minimal.
      Further sensitivity analysis demonstrated that the initial SE contamination level
      significantly influenced the final exposure levels only under no-abuse or mildly
      abusive conditions. The results of our study suggest that, for maximum reduction
      of SE exposure level, cooling strategies should not only focus on the on-farm or
      processing phases, but should emphasize the importance of cooling strategies at
      the distribution and consumer phases of the farm-to-fork continuum.

PMID- 11999120
TI  - Responses of Listeria monocytogenes to acid stress and glucose availability
      monitored by measurements of intracellular pH and viable counts.
AB  - Physiological aspects of the response of Listeria monocytogenes to acidic
      conditions and effect of glucose availability were studied by fluorescence ratio
      imaging microscopy (FRIM) as compared with traditional viable counts. Three types
      of experiments were conducted: (i) static with measurements of intracellular pH
      (pHi) at extracellular pH (pHo) values ranging from pH 3.0 to 6.0 at 0.5 pH unit
      intervals; (ii) kinetic with monitoring of bacterial responses to changes in the
      pHo from the value of 6.0 to 4.0 or 3.0; (iii) survival experiments studying
      bacterial recovery in response to a shift to favourable conditions after a
      treatment at low pH. All the experiments were performed at three levels of
      glucose in the medium (0, 1, and 10 mM). Both survival and pHi were greatly
      affected by pHo and glucose availability with the highest values for CFU and pHi
      at highest glucose concentration and pHo values in the medium in all trials. A
      high correlation (R2 = 0.995) between pHi and CFU counts was observed. The pH
      gradient started to collapse at pHo 4 and below for trials with glucose in the
      medium and at pHo 5.5 and below without glucose. A recovery step was proposed
      after the apparently lethal treatment to assess cell viability by FRIM.

PMID- 11999121
TI  - Growth and aroma production by Staphylococcus xylosus, S. carnosus and S. equorum
      -a comparative study in model systems.
AB  - A laboratory medium inoculated with 20 different Staphylococcus strains was
      prepared in accordance with a full factorial experimental design investigating
      the effect of temperature, pH, NaCl and glucose on growth. The 12 strains most
      suited to growth in a fermented meat environment were inoculated in sausage
      minces together with Pediococcus pentosaceus, incubated at 25 degrees C for 1
      week and the produced aroma compounds collected. The data were analysed by
      multiple linear regression and partial least squares regression analysis. The
      results showed that increasing pH and temperature from 4.6 to 6.0 and 10 to 26
      degrees C, respectively, increased growth of all strains with strong synergy
      between temperature and pH. Increasing salt concentration from 5% to 15% w/v
      decreased growth of most strains, but the effect of pH and temperature was much
      stronger than the effect of salt. Strains of S. carnosus were more salt tolerant
      than strains of S. equorum and S. xylosus, especially at high pH and temperature.
      Addition of glucose up to 0.5% w/v had no significant influence on growth of any
      of the strains. With regard to aroma production, species characteristics were
      detected. S. carnosus and S. xylosus were quite different regarding the overall
      aroma profiles, whereas the profiles of S. equorum lied somewhere in-between.
      Contrary to S. carnosus, S. xylosus and S. equorum did not produce 2-methyl-1
      butanol. On the other hand, in particular, S. xylosus produced more 3-methyl-1
      butanol. Except for one of the strains of S. equorum, S. xylosus and S. equorum
      formed more diacetyl, 2-butanone and acetoin and also more of the methyl-branched
      ketones arising from degradation of leucine, isoleucine and valine. S. carnosus
      produced more methyl-branched aldehydes, acids and corresponding esters from
      leucine, isoleucine and valine compounds that have been correlated with fermented
      sausage maturity in former studies. S. equorum produced the least of the methyl
      branched aldehydes.

PMID- 11999122
TI  - Natural products as targeted modulators of the nuclear factor-kappaB pathway.
AB  - The use of plant extracts to alleviate inflammatory diseases is centuries old and
      continues to this day. This review assesses the current understanding of the use
      of such plants and natural products isolated from them in terms of their action
      against the ubiquitous transcription factor, nuclear factor kappa B (NF-kappaB).
      As an activator of many pro-inflammatory cytokines and inflammatory processes the
      modulation of the NF-kappaB transduction pathway is a principal target to
      alleviate the symptoms of such diseases as arthritis, inflammatory bowel disease
      and asthma. Two pathways of NF-kappaB activation will first be summarised,
      leading to the IKK (IkappaB kinase) complex, that subsequently initiates
      phosphorylation of the NF-kappaB inhibitory protein (IKB). Natural products and
      some extracts are reviewed and assessed for their activity and potency as NF
      kappaB inhibitors. A large number of compounds are currently known as NF-kappaB
      modulators and include the isoprenoids, most notably kaurene diterpenoids and
      members of the sesquiterpene lactones class, several phenolics including curcumin
      and flavonoids such as silybin. Additional data on cellular toxicity are also
      highlighted as an exclusion principle for pursuing such compounds in clinical
      development. In addition, where enough data exists some conclusions on structure
      activity relationship are provided.

PMID- 11999123
TI  - In-vitro release and oral bioactivity of insulin in diabetic rats using
      nanocapsules dispersed in biocompatible microemulsion.
AB  - This study evaluated the potential of poly(iso-butyl cyanoacrylate) (PBCA)
      nanocapsules dispersed in a biocompatible microemulsion to facilitate the
      absorption of insulin following intragastric administration to diabetic rats.
      Insulin-loaded PBCA nanocapsules were prepared in-situ in a biocompatible water
      in-oil microemulsion by interfacial polymerisation. The microemulsion consisted
      of a mixture of medium-chain mono-, di- and tri-glycerides as the oil component,
      polysorbate 80 and sorbitan mono-oleate as surfactants and an aqueous solution of
      insulin. Resulting nanocapsules were approximately 200 nm in diameter and
      demonstrated a high efficiency of insulin entrapment (> 80%). In-vitro release
      studies showed that PBCA nanocapsules could suppress insulin release in acidic
      media and that release at near neutral conditions could be manipulated by varying
      the amount of monomer used for polymerisation. Subcutaneous administration of
      insulin-loaded nanocapsules to diabetic rats demonstrated that the bioactivity of
      insulin was largely retained following this method of preparing peptide-loaded
      nanocapsules and that the pharmacodynamic response was dependent on the amount of
      monomer used for polymerisation. The intragastric administration of insulin
      loaded nanocapsules dispersed in the biocompatible microemulsion resulted in a
      significantly greater reduction in blood glucose levels of diabetic rats than an
      aqueous insulin solution or insulin formulated in the same microemulsion. This
      study demonstrates that the formulation of peptides within PBCA nanocapsules that
      are administered dispersed in a microemulsion can facilitate the oral absorption
      of encapsulated peptide. Such a system can be prepared in-situ by the interfacial
      polymerisation of a water-in-oil biocompatible microemulsion.

PMID- 11999124
TI  - Calorimetric studies of diclofenac sodium in aqueous solution of cyclodextrin and
      water-ethanol mixtures.
AB  - The technique of solution calorimetry has been employed to study the interaction
      between diclofenac sodium and beta-cyclodextrin by determining the enthalpies of
      solution of the drug in water and in aqueous beta-cyclodextrin solution.
      Thermodynamic parameters characterizing the binding process such as enthalpy
      deltaH0, equilibrium constant K, free energy deltaG0 and entropy deltaS0 have
      been calculated to be 12.00 kJ mol(-1), 1670 dm3 mol(-1), -19.03kJ mol(-1) and
      22.98 J K(-1) mol(-1), respectively. Enthalpies of solution of diclofenac sodium
      have also been determined in water-ethanol mixtures.

PMID- 11999125
TI  - Development of a lyophilised RH1 formulation: a novel DT diaphorase activated
      alkylating agent.
AB  - RH1 is a novel aziridinylbenzoquinone alkylating agent, which is activated in
      tumour cells by DT diaphorase. In common with previous aziridinylbenzoquinones,
      RH1 exhibits limited aqueous stability and solubility. The aim of this study was
      to examine the pharmaceutical properties of RH1 with a view to preparing a
      suitable formulation for clinical trial. Stability in a neutral phosphate
      buffered solution was poor with a degradation half-life of 50 h at 55 degrees C,
      indicating that lyophilisation was preferable. The reaction kinetics indicated a
      similarity with previous studies for base-catalysed degradation of
      aziridinylbenzoquinones. Intrinsic aqueous solubility at 0.5 mg mL(-1) may be
      increased in solvent systems or by the use of polymers such as
      polyvinylpyrrolidone (PVP) or complexing agents like hydroxypropyl-beta
      cyclodextrin (HPBCD). In the latter case this increased solubility by an order of
      magnitude to around 5 mg mL(-1). Four potential formulations based on
      lyophilisation of RH1 (1 mg mL(-1)) from buffered solution (pH 7, 0.01 M NaH2PO4)
      containing either 50 mg mL(-1) mannitol, 40 mg mL(-1) dextran, 20 mg mL(-1) PVP
      or 50 mg mL(-1) HPBCD were prepared and examined for stability characteristics.
      All formulations exhibited a temperature-dependent degradation. The mannitol and
      dextran formulations had limited stability and degraded rapidly at all
      temperatures. The PVP and HPBCD formulations degraded at elevated temperatures
      but remained stable for up to twelve months at 4 degrees C. Examination of the
      degradation kinetics in the latter systems demonstrated similarity to the
      solution degradation mechanism, while in the former alternative degradation
      pathways appeared to be occurring. The chemical stability of RH1 in lyophilised
      formulations is dependent upon the excipient employed and storage temperature.
      Either the PVP or HPBCD formulation would be suitable clinical trial formulations
      of RH1. The results indicate that the choice of lyophilisation excipient for
      aziridinylbenzoquinones cannot be based on previous literature studies of related
      agents.

PMID- 11999126
TI  - Formation of a disulfide protein conjugate of the SH-group-containing metabolite
      (M-I) of esonarimod (KE-298) and its elimination in rats.
AB  - The reactivity of the thiol moiety of the active main metabolite (M-I) of
      esonarimod (KE-298), a novel anti-rheumatic agent, was investigated in rats.
      After repeated oral administration of 14C-KE-298, the radioactivity decreased
      rapidly and no tendency towards accumulation was found, in marked contrast to
      other common SH-group-containing drugs. At 30 min after intravenous
      administration of 14C-M-I to rats, the concentration of the 14C-M-I plasma
      protein conjugate in plasma was extremely low at 0.143 nmol mL(-1) (0.66% of
      total plasma radioactivity). The 14C-M-I plasma protein conjugate that formed in
      rat plasma was mixed disulfide with plasma protein. After intravenous
      administration of synthetic 14C-M-I plasma protein conjugate to rats, the
      radioactivity in plasma decreased rapidly, with the terminal half-life at 6.90 h.
      In-vitro, the 14C-M-I plasma protein conjugate was readily dissociated by the
      endogenous thiol compounds, cysteine and glutathione. These results suggest that
      the reactivity of the thiol moiety of M-I is extremely low. Furthermore, the 14C
      M-I plasma protein conjugate decreased rapidly in-vivo, which would be related to
      interaction with endogenous thiol compounds. These properties of M-I are
      principally responsible for the zero accumulation in rat tissues. KE-298 could
      therefore be expected to have reduced adverse effects compared with other SH
      group-containing anti-rheumatic drugs.

PMID- 11999127
TI  - The influence of caprate on rectal absorption of phenoxymethylpenicillin:
      experience from an in-vivo perfusion in humans.
AB  - The aim of this in-vivo perfusion study in humans was to investigate the
      influence of a penetration enhancer, sodium caprate, on the rectal absorption of
      phenoxymethylpenicillin and antipyrine. Six subjects, 3 male and 3 female, were
      included in two separate studies using perfusion solution of different pH (T1 and
      T2, respectively). Each in-vivo rectal perfusion investigation lasted for 200 min
      and consisted of two periods of 100 min, the first serving as a control, and
      sodium caprate being added in the second period in both T1 and T2. The
      concentrations of phenoxymethylpenicillin, antipyrine and sodium caprate in the
      outlet perfusate were assayed by HPLC, as was the plasma concentrations of
      phenoxymethylpenicillin. At pH 6.0 (0-100 min) the fraction absorbed (f(abs)) and
      effective permeability (P(eff)) of phenoxymethylpenicillin were 0.3% and 0.06 x 4
      cm s(-1), respectively, and remained unaffected by the addition of sodium
      caprate. When the same subjects were perfused at pH 7.4, the f(abs) and P(eff) of
      phenoxymethylpenicillin were 2.4% and 0.11 x 10(-4) cm s(-1) (0-100 min),
      respectively, also remaining unchanged by addition of sodium caprate (100-200
      min). It was possible to determine the plasma AUC of phenoxymethylpenicillin
      after addition of sodium caprate in three subjects at both pHs; this was in the
      range of 14.0-62.8 and 56.4-231 (min micromol L(-1)) at pH 6.0 and 7.4,
      respectively. Interestingly, there was a correlation between P(eff) for sodium
      caprate and the individual plasma AUC and C(max) of phenoxymethyl-penicillin,
      which indicates that the permeability of the enhancer in the tissue upon which it
      should act is crucial for achieving an effect. The f(abs) and the P(eff) of
      antipyrine were not affected at either pH when sodium caprate was added to the
      perfusion solution. In conclusion, the plasma pharmacokinetics of
      phenoxymethylpenicillin suggested a slightly increased rectal absorption at pH
      7.4 in subjects where sodium caprate was transported into the rectal tissue.
      However, the increased P(eff) for phenoxymethylpenicillin wastoo small to
      detectfrom the outlet perfusate, which suggests that sodium caprate alone has a
      limited effect on the permeability in-vivo across the rectal epithelium when it
      is presented in a solution.

PMID- 11999128
TI  - Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans.
AB  - As unilateral nephrectomy is not a rare surgical procedure, it gives rise to the
      question whether drugs predominantly eliminated through the urinary tract can be
      handled effectively by the remaining kidney. Amikacin is predominantly excreted
      via glomerular filtration with only a small fraction undergoing tubular
      reabsorption, and can be used as a model drug of glomerular elimination. The
      study was carried out in 28 subjects, 10 one month and 10 one year after
      unilateral nephrectomy, as well as in 8 healthy subjects. The pharmacokinetics of
      amikacin was investigated after a 1-h infusion of 5 mg kg(-1) amikacin. Blood
      samples were collected for 24 h after the end of infusion. Pharmacokinetic
      parameters of amikacin were calculated using a one-compartment open model for
      intravenous administration. Amikacin concentrations were significantly elevated
      in nephrectomized patients as compared with control subjects, both 1 month and 1
      year after the surgery, and were similar at these two time-points following
      unilateral nephrectomy. Pharmacokinetic parameters of amikacin in patients
      subjected to unilateral nephrectomy were significantly different from those
      observed in the control subjects. As compared with the controls, an increase in
      AUC (area under the serum concentration-time curve) by 81% (P < 0.001) and 63% (P
      < 0.01) 1 month and 1 year after nephrectomy was observed, respectively. The
      lambda(z) (elimination rate constant) was reduced by 39% (P < 0.001) after 1
      month and by 38% (P < 0.001) 1 year after the operation and t 1/2 was prolonged
      by 70% (P < 0.001) and by 43% (P < 0.01) at the respective time-points following
      unilateral nephrectomy. CLT (total body clearance of the drug from plasma) and
      CL(BW) (clearance per kg body weight) were both significantly decreased in
      unilaterally nephrectomized subjects in comparison with the controls. CLT and
      CL(BW) were reduced by 53% (P < 0.001) and 42% (P < 0.01) 1 month after
      nephrectomy, and by 45% (P<0.001) and 42% (P<0.01) 1 year after the surgery,
      respectively. No significant differences among studied groups were found in C0
      (initial serum drug concentration) and Vd (apparent volume of distribution). The
      results suggest that unilateral nephrectomy impairs elimination of amikacin, and
      possibly other drugs predominantly eliminated via glomerular filtration.

PMID- 11999129
TI  - Responsiveness, affinity constants and beta-adrenoceptor reserves for
      isoprenaline on aortae from normo-, pre- and hypertensive rats.
AB  - The objective of this study was to determine the responsiveness, affinity
      constants and beta-adrenoceptor reserves for isoprenaline on the isolated aorta
      in the maturation of normotensive and hypertensive rats. The effects of a very
      slowly reversible antagonist, bromoacetylal-prenololmenthane (BAAM), on the
      relaxant responses of the aortae of 5- and 14-week-old Wistar Kyoto normotensive
      rats (WKY) and spontaneously hypertensive rats (SHRs) to isoprenaline were
      determined. Five-week-old SHRs are pre-hypertensive and the aortic rings are less
      responsive to isoprenalinethan age-matched WKY (pD2 values: WKY, 8.40; SHRs,
      8.03). Similar relaxant responses to forskol in were obtained on the aortae of 5-
      and 14-week-old WKY and SHRs. The K(A) value for isoprenaline at the aortic beta2
      adrenoceptors of the 5-week-old WKY was 2.1 x 10(-7) M, and similar values were
      obtained on the aortae of 5-week-old SHR and 14-week-old WKY and SHRs. In the
      maturation of the WKY aortae from 5 to 14 weeks, there was a reduction in the
      maximum response, a major loss of sensitivity and a loss of beta2-adrenoceptor
      reserve for isoprenaline. On 5-week-old SHR aorta, the sensitivity to
      isoprenaline was 2.5-fold lower, and the beta2-adrenoceptor reserve was less than
      on age-matched WKY. In the development of hypertension on the SHR aorta from 5 to
      14 weeks, there was a reduction in the maximum response to isoprenaline. At 14
      weeks, the sensitivity and the beta-adrenoceptor reserve to isoprenaline were
      similar, but the maximum responses were lower on the SHR than WKY. As there are
      differences in pre-hypertensive SHR and age-matched WKY aortic responses to
      isoprenaline, it is no longer valid to consider that the loss of responsiveness
      to isoprenaline in hypertension is solely owing to the hypertension. There are no
      changes in affinity, but major changes in the sensitivity, maximum responses and
      aortic beta2-adrenoceptor reserves to isoprenaline in the maturation of
      normotensive and pre-hypertensive aortae.

PMID- 11999130
TI  - Hormonal influence on the release of endothelial nitric oxide: gender-related
      dimorphic sensitivity of rat aorta for noradrenaline.
AB  - Male gender shows a higher incidence of vascular disorders and this phenomenon
      could be explained by sexual dimorphic behaviour of vessels. Both gonadal
      hormones and endothelial nitric oxide (NO) are involved in the regulation of the
      vascular reactivity. This study aimed to evaluate a possible sexual dimorphic
      sensitivity of rat aorta for the catecholamine noradrenaline. To understand the
      role played by physiological concentrations of sex hormones, the experimental
      procedures were performed on isolated preparations from intact (sham-operated)
      and gonadectomized rats of both sexes. In parallel sets of experiments, the
      biosynthesis of NO was inhibited by N'-nitro-L-arginine methyl ester (L-NAME) to
      reveal any potential involvement of the endothelial modulator and its possible
      link with the endocrinous factor. In aortae from intact male and female rats,
      noradrenaline induced contractile effects with different potencies (mean+s.d.
      EC50 values 12.15 +/- 5.25 nM and 84.10 +/- 18.68 nM, respectively). Gonadectomy
      resulted in an increased sensitivity for noradrenaline in female vessels and a
      decreased sensitivity for the agonist in male vessels (EC50 values 25.64 +/- 5.04
      nM and 21.70 +/ 1 1.13 nM, respectively). In aortae from intact male rats, the
      inhibition of NO biosynthesis resulted in a weak increase in sensitivity for
      noradrenaline (EC50 value 6.08 +/- 4.53 nM), whereas the increase was higher in
      vessels from intact female rats (EC50 value 10.38 +/- 8.40 nM). After treatment
      with L-NAME, aortae from gonadectomized male and female rats presented almost
      equivalent increases in sensitivity for the adrenergic agonist (EC50 values 6.02
      +/- 3.63 nM and 9.10+/- 9.63 nM,respectively),and no significant difference in
      sensitivity could be recorded between intact and orchidectomized male rats, or
      between intact and ovariectomized female rats. It was concluded that rat aorta
      showed a sexual dimorphic sensitivity for noradrenaline and the female sex was
      more protected against the adrenergic contractile stimulus because of a higher
      release of endothelial NO. The gender-related difference in NO release was
      influenced by gonadal hormones, with the female hormones inducing an increase and
      the male hormones causing a reduction.

PMID- 11999131
TI  - Efficacy of lactosaminated and intact N-succinylchitosan-mitomycin C conjugates
      against M5076 liver metastatic cancer.
AB  - In this study,lactosaminated N-succinyl-chitosan (Lac-Suc) was investigated for
      its liver targeting ability in the early metastatic stage of liver cancer, and
      subsequently Lac-Suc-mitomycin C conjugate (Lac-Suc-MMC) and highly-succinylated
      N-succinyl-chitosan (Suc(II))-MMC conjugate (Suc(II)-MMC) were examined for
      efficacy against the liver metastasis. Mice into which M5076 cells were
      inoculated intravenously were used as liver metastatic models. Fluorescently
      labelled Lac-Suc (Lac-Suc-FTC) was intravenously administered at a daily dose of
      0.2 mg/mouse for 4 days or at a single dose of 0.8 mg/mouse at 3 days post
      inoculation. At a dose of 0.2 mg/mouse for 4 days, liver accumulation of Lac-Suc
      FTC was increased after all except the fourth injection, indicating that the
      capacity of accumulation might be limited to around 110 microg per mouse with
      repeated daily administration at 0.2 mg/mouse. As to the efficacy of intravenous
      administration at 7 days post-inoculation, Lac-Suc-MMC was less effective at a
      dose of 1 mg kg(-1) for 4 days than a single dose of 4 mg kg(-1). This result was
      not in accordance with that expected from the biodistribution study. On the other
      hand, with intravenous administration at 3 days post-inoculation, Suc(II)-MMC was
      more effective on repeated administration, and it showed higher efficacy than Lac
      Suc-MMC at both 1 mg kg(-1) for 4 days and 4 mg kg(-1) as a single dose. Further,
      with intravenous administration at 3 days post-inoculation, Suc(II)-MMC exhibited
      a much higher survival effect at a dose of 4 mg kg(-1) for 4 days.

PMID- 11999132
TI  - Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand
      binding techniques.
AB  - Prostaglandins such as prostaglandin E2 (PGE2) interact with EP-class prostanoid
      receptors including EP1, EP2, EP3 and EP4 subtypes. We have conducted a detailed
      pharmacological characterization of the binding of [3H]-PGE2 to recombinant human
      EP1 prostanoid receptors expressed in human embryonic kidney (HEK-293) cells
      using a broad panel of natural and synthetic prostanoids. The receptor displayed
      high affinity (Kd = 16.0 +/- 0.69 nM; n = 3) for [3H]-PGE2, and was expressed at
      high levels (Bmax =3.69 +/- 0.30 pmol (mg protein)(-1)) in cell membranes of HEK
      293 cells. Specific binding constituted 97.5 +/- 1.4% (n = 12) of the total
      binding. In competition assays, the rank order of affinities of natural
      prostanoids for the receptor was PGE2 > PGE1 > PGF2 > PGI2 > PGD2. PGE2 was more
      effective than PGE1 at displacing bound [3H]-PGE2 (Ki for PGE2 = 14.9 +/- 2.2 nM;
      Ki for PGE1 = 165 +/- 29 nM). The affinities of enprostil (Ki = 14.5 +/- 3.1 nM)
      and 17-phenyl-omega-trinor-PGE2 (Ki = 7.3 +/- 2.7 nM) for the receptor were quite
      similar to that of PGE2, while that of sulprostone (Ki = 137 + 13 nM) more
      closely resembled PGE1. Some compounds historically classified as specific for DP
      prostanoid receptors bound with relatively high affinity to the recombinant human
      EP1 receptor (e.g. ZK118182 (K = 73.4 +/- 8.6 nM) and ZK110841 (K = 166 +/- 20
      nM)). All FP (e.g. travoprost acid, fluprostenol), IP (iloprost) and TP (SQ29548)
      receptor-specific ligands exhibited low affinity (Ki > or = 1 microM).

PMID- 11999133
TI  - A study of the substrate specificity of Na+-dependent and Na+-independent neutral
      amino acid transport systems in dog intestinal brush-border membrane vesicles
      using L-alanine analogues.
AB  - Neutral amino acids are mainly transported across the intestinal brush-border
      membrane by two Na+-dependent systems (system B0 and system B0+) and one Na+
      independent system (system b0,+). To investigate potential differences in
      substrate specificity between these systems, we screened ten different alanine
      analogues for their ability to inhibit the transport of L-alanine in dog
      intestinal brush-border membrane vesicles. The results suggested that a phenyl
      group directly attached to the alpha-carbon has different effects on the Na+
      dependent and Na+-independent transport systems, with an increased affinity for
      the former and a decreased affinity for the latter. Based on these inhibition
      studies, we investigated [14C]L-phenylglycine transport kinetics in comparison
      with L-alanine. Similar to L-alanine, L-phenylglycine transport followed at least
      three routes, however, the Km of the Na+-dependent transport system was lower and
      the K'm of the Na+-independent system was higher than the corresponding values
      for L-alanine. These results corroborated the conclusions drawn from the
      inhibition studies. Based on these data, we conclude that different sizes of
      immediate parts to the alpha-carbon in functional groups of amino acid analogues
      have differential effects on the interaction of these amino acid analogues with
      the Na+-dependent and Na+-independent transport systems for neutral amino acids.

PMID- 11999134
TI  - Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or
      carbon tetrachloride in rats.
AB  - This study was carried out to investigate the antifibrotic effects of methanol
      extracts from the traditional Chinese medicinal herb, the root of Scutellaria
      baicalensis Georgi, on liver fibrosis induced by bile duct ligation and scission
      (BDL) or carbon tetrachloride (CCl4) in rats. Liver fibrosis was assessed by
      histological observations and by measuring levels of liver hydroxyproline, lipid
      peroxidation based on malondialdehyde (MDA) production, and serum enzyme
      activities. The morphological characteristics of livertissuewere examined by
      Masson'strichrome staining and immunostaining against smooth muscle cell alpha
      actin. In both models, the levels of hydroxyproline and MDA in liver were
      significantly increased. Treatment with a methanol extract of S. baicalensis
      significantly reduced the levels of liver hydroxyproline and MDA, with improved
      histological findings. In both models, the liver areas positive for smooth muscle
      cell alpha-actin were considerably decreased by treatment with oral methanol
      extract of S. baicalensis (150 mg kg(-1) daily for 28 days). A methanol extract
      of S. baicalensis root inhibits fibrosis and lipid peroxidation in rat liver
      induced by BDL or CCl4.

PMID- 11999135
TI  - The output of flunisolide from different nebulisers.
AB  - The objective of this study was to determine the output, in-vitro, solution of a
      concentrated solution of flunisolide from two different nebulisers under
      simulated breathing conditions. The BimboNeb and Nebula nebulisers were used to
      nebulise 2.6 mL of flunisolide solution (600 microg). Particle size was
      determined by inertial impaction and the total output of drug from the nebulisers
      under simulated breathing conditions was measured using a sinus flow pump. Two
      different breathing patterns were used, simulating nebuliser use by a child and
      an adult. The mass median aerodynamic diameter of flunisolide particles from the
      BimboNeb and Nebula were both 3.9 microm. With the simulated paediatric breathing
      pattern, both nebulisers delivered similar amounts of flunisolide (56.4 microg
      (s.d. 1.4 microg) and 56.1 microg (5 microg) over 5 min from the BimboNeb and
      Nebula, respectively). With the adult breathing pattern, flunisolide delivery
      from the BimboNeb was increased to 88.9 microg (3.3 microg), but delivery from
      the Nebula was only slightly increased to 64.6 microg (1.4 microg). With both
      nebulisers, little drug was released after 5 min of nebulisation. Both nebulisers
      delivered 9-15% of the nominal dose of flunisolide to the breathing simulator, a
      similar percentage to previous studies with budesonide and more than previous
      studies with beclometasone. Drug delivery from the BimboNeb, but not the Nebula,
      was affected by the simulated breathing pattern. This study suggests that drug
      delivery from nebulisers is dependent upon the interaction between the nebuliser,
      the drug and the patient.

PMID- 11999136
TI  - Preventive effects of a traditional Chinese formulation, Chaihu-jia-Longgu-Muli
      tang, on intimal thickening of carotid artery injured by balloon endothelial
      denudation in rats.
AB  - We report here that the traditional Chinese formulation, Chaihu-jia-Longgu-Muli
      tang (CLM), significantly inhibited the increase in intimal thickening in rat
      carotid artery injured by balloon endothelial denudation, which mimics many
      aspects of restenosis after percutaneous coronary intervention (PCI) in humans.
      CLM, Saiko-ka-Ryukotsu-Borei-to in Japanese, is commonly prescribed for symptoms
      accompanying hypertension and atherosclerosis in Japanese Kampo medical care. CLM
      administered orally 1 week before and 1, 4 and 8 weeks after balloon injury
      inhibited the increase in intimal area, intimal/medial ratio and stenosis ratio.
      To our knowledge, this is the first report demonstrating inhibitory effects of a
      traditional Chinese formulation on intimal thickening of carotid artery after
      balloon injury. It is worth noting that CLM maintained its inhibitory effect up
      to 8 weeks after balloon injury. The reduction in intimal thickening by CLM could
      have resulted from inhibition of intimal smooth muscle cell proliferation, which
      was assessed by immuno-histochemical analysis using monoclonal antibody against
      proliferating cell nuclear antigen. Therefore, CLM may be a favourable candidate
      for prevention of restenosis after PCI. Moreover CLM may have a therapeutic value
      in the prevention of atherosclerosis, because restenosis after PCI is considered
      to be an accelerated atherosclerosis.

PMID- 11999137
TI  - Non-steroidal anti-inflammatory drugs inhibit epinephrine- and cAMP-mediated
      lipolysis in isolated rat adipocytes.
AB  - Acute ethanol intoxication increased triacylglycerides (TAG) and thiobarbituric
      acid reactive substances (TBARS) in liver and promoted the liberation of
      epinephrine. Four non-steroidal anti-inflammatory drugs (NSAIDs)--aspirin,
      naproxen, nimesulide and piroxicam--prevented this increase in TAG and TBARS.
      Because fatty acids provided by adipose tissue contribute substantially to
      elevated hepatic TAG in ethanol-intoxicated rats, it was thought that the NSAIDs
      might reduce epinephrine-stimulated lipolysis in these rats. Isolated rat
      adipocytes were activated with epinephrine in the presence or absence of the
      NSAIDs. The NSAIDs inhibited epinephrine-stimulated lipolysis. These drugs did
      not modify the binding of dihydroalprenolol (beta-adrenergic agonist) to their
      receptors in isolated guinea-pig liver membranes. The NSAIDs, at concentrations
      3,000-fold lower than that of cAMP, inhibited stimulated lipolysis by this
      messenger. In conclusion, aspirin, naproxen, nimesulide and piroxicam reduce the
      release of fatty acids from adipose tissue to the liver by inhibiting the
      epinephrine-stimulated lipolysis, and this, in part, explains the protective
      action of these NSAIDs against hepatic signs of acute ethanol intoxication.

PMID- 11999138
TI  - Gastroprotective activity of oleanolic acid derivatives on experimentally induced
      gastric lesions in rats and mice.
AB  - The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on
      gastric ulceration in rats. The effect of a single oral dose of OA was evaluated
      at 50, 100 and 200 mg kg(-1) in the following models: pylorus ligature (Shay),
      and aspirin- and ethanol-induced gastric ulcers. A single oral administration of
      OA at doses of 50, 100 and 200 mg kg-' inhibited the appearance of gastric
      lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature
      and aspirin models, the effect of OA at the selected concentrations was
      comparable with that of ranitidine at 50 mg kg(-1). In the ethanol-induced
      gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg
      kg(-1) was as active as omeprazole at 20 mg kg(-1). The effect of OA, its
      acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were
      assessed on HCI/ethanol-induced ulcers in mice at 200 mg kg(-1). OA and its
      methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in
      this animal model. The semisynthetic derivatives OAM and OAAM had the greatest
      gastroprotective activity, but their effect was not significantly greater than
      OA. In an acute toxicity test on mice, intraperitoneal administration of OA
      showed no toxicity at doses up to 600 mg kg(-1).

PMID- 11999139
TI  - Usage of triptans among migraine patients: an audit in nine GP practices.
AB  - A retrospective audit was carried out to investigate triptan usage over a period
      of one year among 360 adult patients with migraine in nine GP practices in the UK
      and the Republic of Ireland. Data from patient records were analysed, in
      conjunction with replies to a questionnaire about patients' perceptions of their
      migraine and its treatment. The majority of patients included in the audit were
      women (83%), and most patients (81%) were aged between 35 and 64 years. Most
      patients in the audit population (60%) were in the lowest band of triptan usage
      (1-36 tablets prescribed over 12 months); 7% had moderate usage (37-53 tablets).
      A minority of patients appeared to be taking triptans in higher quantities: about
      15% of patients had been prescribed 54-94 triptan tablets over a year, 9% had
      received prescriptions for 95-149 tablets and 7% had received prescriptions for
      150 or more tablets. These results indicated that some migraine patients were
      using triptans at higher than expected rates, and suggested that some patients
      might have been using their prescribed triptans inappropriately to treat a
      headache that they incorrectly perceived as migraine (e.g. chronic daily
      headache). Analyses were carried out to identify predictors of high usage.
      Predictors identified included the use of several other (non-triptan) medications
      to treat conditions other than migraine, one triptan dose being reported as
      sufficient to treat an attack, patient's perception of all headaches as migraine
      and lack of concern about taking too much medication. Patients identified as
      using triptans at a higher than expected rate can be called in for review of
      migraine diagnosis, identification of possible causes of any increased frequency
      of attacks, and investigation of suspected non-migrainous headaches, such as
      chronic daily headache and medication-induced headaches. For GPs, such actions
      would help achieve and maintain a high standard of care for their migraine
      patients, thus helping to contribute towards meeting the demands of the clinical
      governance agenda. Audit of triptan usage may also offer financial benefits for
      the practice, since helping patients to avoid the inappropriate use of triptans
      could lead to reductions in the overall costs of triptan prescribing within the
      practice. The high usage predictors could be developed into a checklist of
      potential indicators for GPs to identify patients who may become high users if
      prescribed triptans and who might require closer monitoring. We recommend that
      patients identified as having a potential for high usage should be routinely
      reviewed, every 3-6 months, to ensure that they are using triptans appropriately
      to treat migraine. Although triptans are generally safe and well tolerated,
      unnecessary use of any medication should be avoided.

PMID- 11999140
TI  - Cardiovascular properties of the kallikrein-kinin system.
AB  - All the components of the kallikrein-kinin system are located in the vascular
      smooth muscle as well as in the heart. In recent years, numerous observations
      obtained from clinical and experimental models of diabetes, hypertension, cardiac
      failure, ischaemia, myocardial infarction and left ventricular hypertrophy, have
      suggested that the reduced activity of the local kallikrein-kinin system may be
      instrumental in the induction of cardiovascular-related diseases. The ability of
      kallikrein gene delivery to produce a wide spectrum of beneficial effects makes
      it an excellent candidate in treating hypertension, and cardiovascular and renal
      diseases. In addition, stable kinin agonists may also be available in the future
      as therapeutic agents for cardiovascular and renal disorders.

PMID- 11999141
TI  - The onset of action and the analgesic efficacy of Saridon (a
      propyphenazone/paracetamol/ caffeine combination) in comparison with paracetamol,
      ibuprofen, aspirin and placebo (pooled statistical analysis).
AB  - The objective was to evaluate the onset of action, analgesic efficacy and
      tolerability of Saridon*, a propyphenazone 150 mg/paracetamol 250 mg/caffeine 50
      mg combination, in comparison with paracetamol 500 mg, aspirin 500 mg, ibuprofen
      200 mg and placebo, by a pooled statistical analysis of eight studies. Out of 500
      generally healthy patients (55.2% men, 44.8% women), average age 43.5 years, 329
      (65.8%) had moderate and 171 (34.2%) severe acute dentoalveolar pain. More
      Saridon-treated patients reported 'pain gone/partly gone' and less 'pain
      unchanged or worse' compared with paracetamol, aspirin and placebo 30min (p =
      0.009, p < 0.001, p = 0.001, respectively) and 60 min after dosing (p < 0.0001
      for all). The difference with ibuprofen was observed 60 min after dosing (p <
      0.01). Pain intensity differences 30 min and 60 min after dosing infer that
      Saridon has a faster onset of action than all of the other medications that it
      was compared with (ibuprofen at only 60 min after dosing). Total pain relief
      scores four hours after dosing were higher in the Saridon group compared with the
      paracetamol, ibuprofen, placebo (p < 0.0001 for all) and aspirin groups (p <
      0.01). At the end of the study, patients assessed Saridon as more efficacious
      than the other study medications (p < 0.0001 for all). No serious adverse events
      were observed with any of the drugs studied. All medications were well tolerated.
      Twenty patients (4.0%) reported adverse events with no significant differences
      between groups. The most common adverse events were gastrointestinal disorders,
      followed by nervous system, skin, subcutaneous tissue, respiratory, cardiac and
      general disorders. Saridon is an effective analgesic that combines the advantage
      of fast onset and effective analgesia as compared with paracetamol alone,
      ibuprofen, aspirin or placebo. The results of this pooled analysis of eight
      studies should be confirmed in a double-blind study, since seven of the studies
      included in this analysis were single blind.

PMID- 11999142
TI  - Recent advances in breast cancer (the Twenty-fourth San Antonio Breast Cancer
      Symposium, December, 2001).
AB  - This paper reviews the Twenty-fourth Annual San Antonio Breast Cancer Symposium.
      The preliminary results of the ATAC study have shown that Arimidex is superior to
      tamoxifen in postmenopausal women with ER-positive early breast cancer in terms
      of DFS, adverse effects and prevention of contralateral breast cancer. However,
      longer follow up is required to assess the drug safety regarding bone mineral
      density and cognitive function. Letrozole seems to be superior to tamoxifen as a
      first-line therapy in ER-positive advanced breast cancer in postmenopausal women.
      Although the incidence of acute myeloid leukaemia is significantly increased
      (cumulative incidence at 5 years = 1.1%) in breast cancer patients receiving
      cyclophosphamide and anthracyclines, the risk of this complication is easily
      outweighed by the benefits of chemotherapy. Adjuvant clodronate was found to be
      associated with a significant reduction in the incidence of bone metastases
      during the treatment period. A randomised trial comparing axillary dissection and
      axillary radiotherapy (RT) for early breast cancer reported no significant
      difference in survival at 15 years. However, axillary recurrence was
      significantly increased in the RT group. hTERT protein expression by IHC was
      found to correlate significantly with breast cancer-specific survival. There is
      no evidence to support the use of IHC of the sentinel node in routine clinical
      practice. LCIS is currently considered as a non-obligate precursor to breast
      cancer rather than just a risk factor.

PMID- 11999143
TI  - The evolving role of mammary ductoscopy.
AB  - Mammary ductoscopy (MD) is an emerging technique that allows direct visualisation
      of the mammary duct system, and that produces sharp and clear video images and
      ductal washings for cytological analysis. There is a growing body of evidence
      that MD may have a role in the management of women with pathological nipple
      discharge, the guiding of breast conserving surgery for cancer, and the screening
      of high risk women. Further research is required to confirm these potential
      applications and the feasibility of its use in the rapid intervention and
      outpatient setting under local anaesthesia. Furthermore, the addition of
      molecular and genetic analysis of cells obtained by MD and the emergence of newer
      generations of microendoscopes are likely to enhance the use of this technique.

PMID- 11999144
TI  - Second Consensus Conference on Cardiovascular Risk Factors and Erectile
      Dysfunction.

PMID- 11999145
TI  - Beyond LDL-C--the importance of raising HDL-C.
AB  - Epidemiological studies have established that low levels of high-density
      lipoprotein cholesterol (HDL-C) are associated with an increased risk of coronary
      heart disease (CHD). Recent studies have demonstrated that low HDL-C levels, and
      high triglycerides and total cholesterol levels are independent predictors of
      CHD, and that the combination of these lipid abnormalities increases the risk of
      coronary events. In lipid-modifying intervention studies, agents that raise HDL-C
      levels have been shown to reduce the incidence of major coronary events. The VA
      HIT study consisted of patients with low-density lipoprotein cholesterol (LDL-C)
      levels similar to those recommended by several guidelines but with low levels of
      HDL-C. This trial demonstrated that raising HDL-C levels with gemfibrozil reduced
      the risk of CHD-related events. While the mechanisms by which HDL-C exerts its
      anti-atherogenic effects have yet to be fully elucidated, its role in the reverse
      transport of cholesterol and the beneficial effects on endothelial function are
      plausible explanations for these actions. Although LDL-C reduction is the primary
      goal in the treatment of dyslipidaemia, current guidelines recognise low HDL-C
      levels as a major risk factor for CHD. Indeed, the NCEP ATP III guidelines
      suggest that the treatment of isolated low HDL-C levels in CHD patients or
      individuals with CHD risk equivalents should be considered. The differing
      abilities of statins to raise HDL-C levels may be an important factor when making
      treatment decisions. New lipid-modifying drugs with beneficial effects on both
      HDL-C and LDL-C levels would be desirable additions to the currently available
      therapeutic options.

PMID- 11999146
TI  - Patient and physician satisfaction with rofecoxib in osteoarthritis: results of
      the EVA (experience with VIOXX in arthritis) survey. Current Medical Research and
      Opinion, 17(2): 81-8, 2001.

PMID- 11999147
TI  - Recent advances in the management of age-related macular degeneration.
AB  - Choroidal neovascularization (CNV) secondary to age-related macular degeneration
      (AMD) can cause rapid and severe central vision loss in many older people. Until
      recently, the only treatment proven beneficial was thermal laser
      photocoagulation, which was applicable to only a small subset of patients.
      Furthermore, the thermal laser damaged the retina overlying the CNV, which is
      especially problematic for lesions involving the foveal center. Photodynamic
      therapy is a new treatment consisting of intravenous infusion of a drug that is
      then activated by a low-energy laser, causing damage to CNV. Photodynamic therapy
      with verteporfin (Visudyne, Novartis AG) has been shown to reduce the risk of
      moderate and severe vision loss in patients with predominantly classic subfoveal
      CNV secondary to AMD. With the advent of verteporfin therapy, eye care providers
      will play an increasingly important role in managing patients with AMD,
      especially in the early detection and rapid referral of appropriate cases.

PMID- 11999148
TI  - The optical functional advantages of an intraocular low-vision telescope.
AB  - An implantable miniaturized telescope (IMT) for low vision has recently been
      developed. Surgically inserted into only one eye of patients with bilateral
      central visual loss, the IMT provides a nominal magnification of 3.0x and a field
      of-view of 6.6 degrees (9.2 degrees for the 2.2x magnification version).
      Theoretical concerns have been raised regarding the ability of patients to
      function with a large interocular magnification difference, the impact of the
      monocular restriction of the field-of-view, and the impact of this design on
      depth perception. This article addresses these concerns regarding the design of
      the IMT in comparison with spectacle-mounted telescopes and combined intraocular
      lens/spectacle (or combined contact lens/spectacle) telescopic systems. The
      effective field-of-view (as determined by the combination of both the field-of
      view and the field-of-fixation), the effects of head motion and the vestibular
      reflex, and the disruption of stereo depth perception with a monocular device are
      considered here. Physiological optics considerations of these issues show that
      the IMT may have important advantages over other designs of magnification devices
      for patients with age-related macular degeneration.

PMID- 11999149
TI  - Optical considerations in the contact lens correction of infant aphakia.
AB  - BACKGROUND: Correction of infant aphakia with conventional soft and rigid designs
      induces significant amounts of positive spherical aberration. METHODS: Different
      levels of positive spherical aberration were induced by rigid lenses positioned
      close to the eye. Visual acuity and depth of focus were measured for twelve young
      adult subjects. RESULTS: Positive spherical aberration acts to produce an
      increase in relative depth of focus, but because of the reduction of best visual
      acuity, there is a concurrent decrease in absolute depth of focus. As the
      spherical aberration increases, there is a progressive loss of best-corrected
      visual acuity. CONCLUSIONS: The correction of spherical aberration in contact
      lenses for infant aphakia provides the best theoretical optical conditions for
      normal ocular growth and visual development. We provide examples of the optimal
      aspheric surfaces to minimize spherical aberration in contact lenses for infant
      aphakes.

PMID- 11999150
TI  - The validity of the University of Waterloo Colored Dot Test for Color Vision
      Testing in adults and preschool children.
AB  - PURPOSE: Most color vision tests require a high level of cognitive ability and as
      such are problematic for preschool children and multiply challenged individuals.
      Our goal was to design a color vision test for these groups and evaluate the
      clinical utility for preschool children. METHODS: The University of Waterloo
      Colored Dot Test (UWCDot) for Color Vision Testing requires the subject to
      distinguish a colored disc from seven gray discs. The target disc was a Munsell
      color along the deutan, protan, or tritan confusion line with gray. The first
      phase estimated the sensitivity and specificity of the test for adults. Thirty
      one adults with normal color vision and 21 adults with congenital red-green
      defects participated. In the second phase, the utility of the UWCDot test for
      screening preschool children was determined. Subjects were 281 males and 269
      females aged 2.5 to 5 years with normal vision. Their color vision was also
      assessed with the Standard Pseudoisochromatic Plates, Part 1 (SPP1). RESULTS: The
      sensitivity and specificity of UWCDot for adults approached the values for the
      desaturated D-15 when subjective responses were scored. Monitoring fixational eye
      movements produced sensitivity and specificity values that were similar to the
      anomaloscope. After adjusting the scoring criterion for the preschool children by
      using the females as a control, 2.9% of the males were identified as red-green
      deficient, 1.8% were blue-yellow deficient, and 3.2% had an unclassified
      deficiency. By definition, 1% of the females failed the test. Counting fixational
      eye movements was not a useful scoring method in the preschool children.
      Comparisons with SPP1 indicated that the UWCDot uncovers approximately 35% of the
      individuals with definite red-green color vision defects. CONCLUSIONS: Our
      results indicate that the UWCDot is capable of detecting approximately 35% of the
      preschool children who have a congenital red-green color vision defect. These
      individuals are likely to have a more severe deficiency.

PMID- 11999151
TI  - Reliability of binocular vision measurements used in the classification of
      convergence insufficiency.
AB  - PURPOSE: To evaluate the reliability of binocular vision measurements used in the
      classification of convergence insufficiency. METHODS: Two examiners tested 20
      fifth and sixth graders in a school setting who passed a screening of visual
      acuity, refraction, and binocularity. The tests, conducted using a standard
      protocol, consisted of von Graefe near heterophoria (NH), phorometric positive
      fusional vergence (PFV), nearpoint of convergence (NPC), and monocular pushup
      accommodative amplitude (AA). Each examiner measured each child three consecutive
      times for each test, on two separate occasions, spaced approximately 1 week
      apart. Intraexaminer and interexaminer agreement was assessed using intraclass
      correlation coefficients (ICC), the median absolute difference (MAD), and the
      coefficient of repeatability (COR). RESULTS: The within-session reliability of
      the NH (ICC: 0.95 to 0.99), NPC (ICC: 0.94 to 0.98), and AA (ICC: 0.88 to 0.95)
      were good, whereas the PFV was less reliable (ICC: 0.71 to 0.94). The
      intraexaminer reliability between sessions was good for the NPC (ICC: 0.92 and
      0.89), less reliable for NH (ICC: 0.81 and 0.81) and AA (ICC: 0.89 and 0.69), and
      much less reliable for PFV break (ICC: 0.59 and 0.53). Typical between-session
      PFV differences (MAD) were between 3 and 4 delta, whereas the COR differences
      were as large as 12 delta. CONCLUSIONS: Three of the four measures (NH, NPC, and
      AA) often used in the classification of convergence insufficiency generally have
      good within-session and between-session reliability. The PFV break was found to
      have only fair reliability with clinically significant differences between
      sessions. The large potential test-retest differences found could complicate
      clinical decision-making in regards to diagnosis and treatment.

PMID- 11999152
TI  - The effectiveness of pencil pushups treatment for convergence insufficiency: a
      pilot study.
AB  - PURPOSE: To study the effectiveness of pencil pushups treatment (PPT) for the
      treatment of convergence insufficiency in a clinical situation. METHODS: PPT was
      prescribed for use at home for 6 weeks for 25 subjects with convergence
      insufficiency. RESULTS: Twelve of the subjects returned for follow-up. Seven of
      12 (58%) subjects showed a clinically significant improvement in nearpoint of
      convergence and positive fusional vergence, and 11 of 12 reported improvement in
      symptoms. Only one subject became asymptomatic. CONCLUSIONS: PPT resulted in some
      improvement in both objective findings and symptoms for some subjects. Compliance
      with the recommended home therapy protocol was poor.

PMID- 11999153
TI  - Do progressing myopes show reduced accommodative responses?
AB  - Refractive error and accommodative responsivity were monitored at 4-month
      intervals over a 1-year period to determine whether an increased lag of
      accommodation either precedes or accompanies the development of myopia.
      Accommodation was measured for stimulus levels of 2.5, 3, 4, and 5 D, and both
      the slope of the stimulus-response function and accommodative error were
      computed. Almost all subjects exhibited accommodative stimulus-response gradients
      close to unity, although a lower gradient was observed in subjects who were
      myopic upon entry into the study and whose ametropia remained stable. These
      stable myopes also exhibited the largest lag of accommodation. These findings do
      not support the proposal that the development of myopia in young adults is
      accompanied by a reduced accommodative response during nearwork.

PMID- 11999154
TI  - Separation of 48V and 48,49Cr in 7Li irradiated Sc2O3 target by liquid-liquid
      extraction.
AB  - A radiochemical heavy ion activation procedure was carried out for the
      simultaneous production of carrier-free 48V and 48,49Cr in 7Li ion irradiated
      Sc2O3 target, followed by the separation of the individual radio-elements in pure
      form through liquid-liquid extraction using liquid cation exchanger, di-(2
      ehtylhexyl) phosphoric acid. Liquid anion exchanger, trioctylamine, was used to
      obtain extractants from aqueous acid solutions under different experimental
      conditions.

PMID- 11999155
TI  - 252Cf: the potential for activation analysis of selected medium-weight and heavy
      elements in the limited neutron flux of a partially depleted 50 microg source.
AB  - A 50 microg 252Cf source, depleted by about 2 orders of magnitude from its
      original neutron output, was used to examine the sensitivity of neutron
      activation analysis for a selection of 20 pure materials and compounds containing
      elements with atomic numbers greater than 40. Generally speaking, the sensitivity
      is seriously restricted by the neutron flux of the source, but in certain
      specific cases the nuclear properties of the elements concerned, such as thermal
      absorption cross-section, isotopic abundance and half-life of the radioactive
      product were considered for the production of a practicable gamma-ray yield. A
      description of the irradiation assembly and the conditions of activation are
      presented. Detection limits varied between 30 microg g(-1) to 8.2 mg g(-1) based
      on the most suitable gamma-ray of the radionuclide of interest. For purposes of
      determining trace and minor concentrations of selected elements, a source of this
      nature could be acquired at a nominal cost especially in developing countries
      that do not have access to a nuclear reactor.

PMID- 11999156
TI  - Model 3500 125I brachytherapy source dosimetric characterization.
AB  - Low-energy gamma-emitting isotopes encapsulated for permanent implant are
      routinely applied in brachytherapy, most notably for prostate cancer. Before
      clinical use of a new source design, a full dosimetric analysis and standardized
      calibration are essential. Results of experimental measurement and analysis are
      reported here for the I-Plant (Implant Sciences Corporation) 125I source, model
      3500. Dose measurements were made using standard methods employing
      thermoluminscent dosimeters in a water equivalent plastic phantom. Precision
      machined bores in the phantom located dosimeters and source(s) in a reproducible
      fixed geometry providing for transverse-axis and angular dose profiles over a
      range of distances from 0.17 to 10 cm. The data were analyzed in terms of
      parameters recommended by AAPM TG-43. The dose-rate constant, delta = 1.01 cGy/h
      U (+/-6%) (1 U = 1 cGy cm2 h(-1)), was evaluated with reference to a TG-51
      calibrated 60Co standard, accounting for dosimeter response differences between
      60Co and 125I photons. The radial dose function, g(r), the anisotropy function,
      F(r, theta), the anisotropy factor, phi(an)(r), and the point-source
      approximation anisotropy constant, phi(an), were derived from one- and two
      dimensional dose distribution data measured in the phantom, accounting for finite
      dosimeter volume and with attention to inter-chip effects. The results confirm
      prior dosimetric characterization of the model 3500, and indicate that the new
      source is comparable to the MED3631-A/M and 6702 source designs and may
      substitute for model 6711 in permanent implants for the treatment of prostate
      cancer.

PMID- 11999157
TI  - Determination of the dosimetric characteristics of InterSource125 iodine
      brachytherapy source.
AB  - The TG-43 recommended dosimetric characteristics of a new 125I brachytherapy
      source have been experimentally and theoretically determined. The measurements
      were performed in Solid Water using LiF TLDs. The calculations were performed
      using Monte Carlo simulations in Solid Water and water. The measured data were
      compared with calculated values as well as the reported data in literature for
      other source designs. The dose rate constant this source in water was 1.01 +/- 3%
      cGy h(-1) U(-1) and the anisotropy constant was 0.956.

PMID- 11999158
TI  - Measurement and evaluation of saturations for water, ethanol and a light non
      aqueous phase liquid in a porous medium by gamma attenuation.
AB  - The gamma attenuation technique is generally used to determine the properties of
      porous media. In this experimental study, this technique was used to define
      porosity, fluid content and liquid saturation of a porous medium. 60Co (1332keV)
      as the gamma source, the Ottawa sand as a homogeneous porous medium and water,
      ethanol, LNAPL (toluene) as liquids were used in the experimental set-up.
      Experiments were performed for all liquids at three stages: the primary
      imbibition, the gravity drainage and the secondary imbibition.

PMID- 11999159
TI  - Determination of the cross section for nuclear reactions in complex nuclear decay
      chains.
AB  - In the present paper decays of genetically connected nuclei are considered and
      equations for their independent cross sections are derived. An optimisation
      parameter is proposed for an experiment where spectra of the residual nuclei are
      studied by the induced activity method. This parameter depends on irradiation
      time, delay time and spectrum measurement time.

PMID- 11999160
TI  - Particle size analysis of radioactive aerosols formed by irradiation of argon
      using 65 MeV quasi-monoenergetic neutrons.
AB  - The size distributions of 38Cl and 39Cl aerosols formed from the irradiation of
      argon gas containing di-octyl phthalate (DOP) aerosols by 65 MeV quasi
      monoenergetic neutrons were measured to study the formation mechanism of
      radioactive aerosols in high-energy radiation fields. Both the number size
      distribution and the activity-weighted size distribution were measured using an
      electrical low-pressure impactor. It was found that the 35Cl and 39Cl aerosols
      are formed by attachment of the radioactive atoms generated by the neutron
      induced reaction to the DOP aerosol particles.

PMID- 11999161
TI  - X-ray irradiation on the soda-lime container glass.
AB  - X-ray irradiation induced defects in the commercial soda-lime container glass
      were studied by means of optical spectrophotometer and ESR. The induced color
      might be applied to producing recyclable glasses. The nonbridging oxygen hole
      centers (NBOHCs) were mainly responsible for the irradiation induced absorptions
      at 431 and 627 nm of glass. The absorption at 305 nm was attributed to the
      trapped electron. The induced deep color can be kept for longer than 7 months,
      but can be almost bleached at 300 degrees C for 20 min.

PMID- 11999162
TI  - A fast automatic RBS/w channeling system for damage depth profiling.
AB  - A computer-aided data acquisition coupling with goniometer-control system
      dedicated for damage depth profile measurements is established. The channeling
      direction searching is performed along tilt and azimuth directions. The system
      includes a computer code to convert the measured spectra into damage depth
      profile. The analyzing time for each sample requires approximately 20-30 min. The
      damage depth profiles of the self-implanted (100) silicon samples are in
      reasonable agreement with the calculated results yielded by the SRIM Monte-Carlo
      simulation code.

PMID- 11999163
TI  - An easy method to determine 210Po and 210Pb by alpha spectrometry in marine
      environmental samples.
AB  - Two 210Po measurements by alpha spectrometry are made in two different aliquots
      separated by sufficient time for the growth of 210Po from the 210Pb content to be
      significant, as a difference from other methods that prepare consecutively, the
      two sources from the same aliquot. The main advantage is that this method is more
      rigorous than others, as it avoids possible error sources in the radiochemical
      procedure and takes care of uncertainties and their propagation. Analyses of
      bivalve samples have validated the method.

PMID- 11999164
TI  - Groundwater dating with radiocarbon: application to an aquifer under semi-arid
      conditions in the south of Morocco (Guelmime).
AB  - Radiocarbon dating is based on measuring the loss of the parent radionuclide
      (14C) in a given sample. This assumes two key features of the system. The first
      is that the initial concentration of the parent is known and has remained
      constant in the past. The second is that the system is closed to subsequent gains
      or losses of the parent, except through radioactive decay. But, the reaction and
      evolution of the carbonate system strongly dilute the initial 14C activity in
      dissolved inorganic carbon (DIC). The result is an artificial "aging" of
      groundwater by dilution of 14C. Unravelling the relevant processes and
      distinguishing 14C decay from 14C dilution is an engaging geochemical problem.
      Several attempts to overcome these problems have been made during the past 30
      years and a number of possible correction procedures have been presented by
      different authors. Environmental isotopes study (13C, 14C) from the aquifers of
      the Guelmime under semi-arid conditions provides new information on recharge
      zones, mixing zones and the circulation routes of water. The combination of
      logP(CO2), the saturation index of dolomite and calcite, HCO3, delta13C, 14C and
      pH along flow paths can provide an indication of open- and closed-system
      conditions in the Oumlaachar and Seyyad sub-basins. This approach of geochemical
      analysis, when combined with correction procedures, allows us to understand age
      and recharge in the Guelmime aquifer. 14C groundwater ages range from modern to
      about 2700 years in this aquifer, and indicate recharge values of 0.55-15 mm/yr.

PMID- 11999165
TI  - Soil radon monitoring in the Krsko Basin, Slovenia.
AB  - In order to support the safe operation of the Krsko Nuclear Power Plant
      (Westinghouse, 676 MWe PWR), the seismotectonic structure of the Krsko basin has
      been thoroughly investigated. As part of a wider study, a study on radon in soil
      gas was started in April 1999. Combined barasol detectors buried in six
      boreholes, two along the Orlica fault and four on either side of it, measure and
      record radon activity, temperature and pressure every 60 min. The results have
      been evaluated and the possibility of a correlation with seismic activity is
      discussed. Correlation between radon concentration and barometric pressure has
      been observed for all barasols. Preliminary results show that, at one location,
      the correlation coefficient between radon and barometric pressure changed sign
      before earthquakes.

PMID- 11999166
TI  - The role of CD4 in regulating homeostasis of T helper cells.
AB  - Intrathymic T cell selection and peripheral activation of mature T cells are
      crucial for self-recognition and the general immune response to viral, bacterial,
      and tumor antigens. The T cell coreceptors, CD4 and CD8, contribute to the
      regulation of these processes. The importance of interactions between CD4 and
      molecules encoded by the class II major histocompatibility complex (MHC) for
      thymic T cell selection has been clearly established, however, the role of CD4
      MHC class II interactions in T helper (TH) cell differentiation, in the
      maintenance of homeostasis in the peripheral immune system, and in the generation
      of memory TH cells is largely unclear. Here, we present evidence for a role of
      CD4 in controlling homeostasis in the peripheral immune system. We also
      demonstrate the importance of CD4-MHC class II interactions in inducing these
      previously not recognized functions of CD4.

PMID- 11999167
TI  - Function and regulation of class II transactivator in the immune system.
AB  - The class II transactivator (CIITA) is a potent and critical transcriptional
      regulator. It activates genes necessary for antigen presentation function. It
      also regulates cytokine gene expression in CD4 T cells. We recently found that
      CIITA prevents cell death by inhibiting Fas ligand (FasL) gene expression. Thus,
      CIITA regulates multiple immune responses. The activation and the repression
      function of CIITA are mediated by its interaction with other transcription
      factors. To activate the target gene, CIITA interacts with DNA binding proteins
      and recruits the coactivator CBP/p300 to the promoter forming an enhanceosome
      necessary for transcription. In addition, CIITA interacts with self. Inter- and
      intramolecular interactions of CIITA are essential for transactivation function.
      Each domain of CIITA has a distinct role and all domains are required for CIITA
      activity. However, the regulatory mechanisms of CIITA interaction with self and
      other proteins are poorly understood and remain to be investigated.

PMID- 11999168
TI  - Use of genetic knockouts to modulate disease expression in a murine model of
      lupus, MRL/lpr mice.
AB  - MRL-MPJ Fas(lpr) (MRL/lpr) mice are a prototypic murine model for lupus
      characterized by an accelerated autoimmune syndrome. Disease begins as early as 8
      wk-of-age in these animals with polyclonal B cell activation and elevated levels
      of serum IgM. By 12 to 16-wk-of-age MRL/lpr mice begin to produce a variety of
      autoantibodies including anti-dsDNA and anti-ss-DNA antibodies. From 16 to 24 wk,
      MRL/lpr mice develop proliferative immune complex mediated glomerulonephritis,
      vasculitis, arthritis, and massive lymphadenopathy that results in renal failure
      and death in 50% of the mice by 24-wk-of-age. This review will discuss several
      different genetic knockout experimental approaches used to study disease
      expression in MRL/lpr mice including various approaches in our laboratory aimed
      at autoantibody (Ab) production and inflammatory mediators.

PMID- 11999169
TI  - Positive and negative roles of CD72 in B cell function.
AB  - Regulation of B cell activation depends on integration of signals transmitted by
      the B cell receptor (BCR) and a variety of co-receptors. CD72 is a B cell co
      receptor that is expressed in all stages of B cell development except plasma
      cells. Ligation of CD72 enhances B cell growth and differentiation. Recently, the
      class IV semaphoring, CD100, has been identified as the natural ligand for CD72.
      Cytoplasmic domain of CD72 has been shown to be associated with SHP-1 leading to
      the proposal that the positive effects of CD72 on B cell response may result from
      sequestration of negative signals from BCR. However, association of CD72 with
      Grb2 and/or CD19 suggests that CD72 could transmit positive signals. Based on
      these data, we propose a dual signaling model of CD72.

PMID- 11999170
TI  - Regulation of experimental autoimmune encephalomyelitis by chemokines and
      chemokine receptors.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a T cell mediated
      demyelinating disease of the central nervous system (CNS) that serves as a model
      for multiple sclerosis (MS). Insights into the pathogenesis of this model may
      help scientists understand the human disease and aid in rational drug discovery.
      In this review we summarize the role of chemokines and chemokine receptors in
      disease pathogenesis and suggest a pathway of events that leads to demyelination
      and subsequent clinical disease manifestation.

PMID- 11999171
TI  - Designing immunotoxins for cancer therapy.
AB  - Immunotoxins are therapeutic agents with a high degree of specificity and unique
      mechanism of action. An immunotoxin is a chimeric protein consisting of a
      targeting moiety linked to a toxin. The targeting moiety selectively binds to a
      tumor cell and targets it for death via the attached toxin. Generally,
      immunotoxins are specifically potent against cancer cells in vitro and in animal
      models of human malignancies. However, immunotoxins can be limited clinically by
      immunogenicity, toxicity, and instability. In this review, we offer ways to
      overcome these limitations to create "ideal immunotoxins" for cancer therapy.
      These include producing single chain targeting/toxin fusion proteins of fully
      human origin that are extracellularly stable but once internalized, can be
      cleaved by intracellular proteases to free the toxin and facilitate its
      translocation to the cytosol.

PMID- 11999173
TI  - Sands shifting beneath our feet.

PMID- 11999172
TI  - Transcytosis and catabolism of antibody.
AB  - This review describes the evolution of our knowledge of the transmission of
      immunoglobulin G (IgG) from mother to infant and the factors which regulate the
      persistence of IgG in the circulation. These apparently unrelated processes
      involve the same Fc receptor, FcRn (n = neonatal). FcRn appears to carry out
      these diverse roles by binding to IgG and then either transporting the bound IgG
      across cells (transcytosis) or recycling its cargo back to the cell surface
      (control of catabolism). IgG that is taken up by cells in the absence of binding
      to FcRn undergoes degradation. Thus, FcRn is the "protective" receptor that
      serves to maintain IgG homeostasis and deliver IgGs across cellular barriers.

PMID- 11999174
TI  - New measures for new roles: defining and measuring the current practices of
      health sciences librarians.
AB  - The roles of academic health sciences librarians are continually evolving as
      librarians initiate new programs and services in response to developments in
      computer technology and user demands. However, statistics currently collected by
      libraries do not accurately reflect or measure these new roles. It is essential
      for librarians to document, measure, and evaluate these new activities to
      continue to meet the needs of users and to ensure the viability of their
      professional role. To determine what new measures should be compiled, the authors
      examined current statistics, user demands, professional literature, and current
      activities of librarians as reported in abstracts of poster sessions at Medical
      Library Association annual meetings. Three new categories of services to be
      measured are proposed. The first, consultation, groups activities such as quality
      filtering and individual point-of-need instruction. The second, outreach,
      includes activities such as working as liaisons, participating in grand rounds or
      morning report, and providing continuing education. The third area, Web
      authoring, encompasses activities such as designing Web pages, creating online
      tutorials, and developing new products. Adding these three measures to those
      already being collected will provide a more accurate and complete depiction of
      the services offered by academic health sciences librarians.

PMID- 11999175
TI  - Variations in Medical Subject Headings (MeSH) mapping: from the natural language
      of patron terms to the controlled vocabulary of mapped lists.
AB  - OBJECTIVES: This study compared the mapping of natural language patron terms to
      the Medical Subject Headings (MeSH) across six MeSH interfaces for the MEDLINE
      database. METHODS: Test data were obtained from search requests submitted by
      patrons to the Library of the Health Sciences, University of Illinois at Chicago,
      over a nine-month period. Search request statements were parsed into separate
      terms or phrases. Using print sources from the National Library of Medicine, Each
      parsed patron term was assigned corresponding MeSH terms. Each patron term was
      entered into each of the selected interfaces to determine how effectively they
      mapped to MeSH. Data were collected for mapping success, accessibility of MeSH
      term within mapped list, and total number of MeSH choices within each list.
      RESULTS: The selected MEDLINE interfaces do not map the same patron term in the
      same way, nor do they consistently lead to what is considered the appropriate
      MeSH term. CONCLUSIONS: If searchers utilize the MEDLINE database to its fullest
      potential by mapping to MeSH, the results of the mapping will vary between
      interfaces. This variance may ultimately impact the search results. These
      differences should be considered when choosing a MEDLINE interface and when
      instructing end users.

PMID- 11999176
TI  - The role of medical libraries in undergraduate education: a case study in
      genetics.
AB  - Between 1996 and 2001, the Health Science Center Libraries and Department of
      Zoology at the University of Florida partnered to provide a cohesive and
      comprehensive learning experience to undergraduate students in PCB3063,
      "Genetics." During one semester each year, a librarian worked with up to 120
      undergraduates, providing bibliographic and database instruction in the tools
      that practicing geneticists use (MEDLINE, GenBank, BLAST, etc.). Students learned
      to evaluate and synthesize the information that they retrieved, coupling it with
      information provided in classroom lectures, thus resulting in well-researched
      short papers on an assigned genetics topic. Exit surveys of students indicated
      that the majority found the library sessions and librarian's instruction to be
      useful. Responses also indicated that the project facilitated increased
      understanding of genetics concepts and appreciation for the scientific research
      process and the relevance of genetics to the real world. The library benefited
      from this partnership on a variety of fronts, including the development of
      skilled library users, pretrained future clientele, and increased visibility
      among campus research laboratories. The course and associated information
      instruction and assigned projects can be considered models for course-integrated
      instruction and the role of medical libraries in undergraduate education.

PMID- 11999177
TI  - Real-time, evidence-based medicine instruction: a randomized controlled trial in
      a neonatal intensive care unit.
AB  - PURPOSE: The study assesses potential for improving residents' evidence-based
      medicine searching skills in MEDLINE through real-time librarian instruction.
      SUBJECTS: Ten residents on a rotation in a neonatal intensive care unit
      participated. METHODOLOGY: Residents were randomized into an instruction and a
      non-instruction group. Residents generated questions from rounds and searched
      MEDLINE for answers. Data were collected through observation, search strategy
      analysis, and surveys. Librarians observed searches and collected data on
      questions, searching skills, search problems, and the test group's instruction
      topics. Participants performed standardized searches before, after, and six
      months after intervention and were scored using a search strategy analysis tool
      (1 representing highest score and 5 representing lowest score). Residents
      completed pre- and post-intervention surveys to measure opinions about MEDLINE
      and search satisfaction. RESULTS: Post-intervention, the test group formulated
      better questions, used limits more effectively, and reported greater confidence
      in using MEDLINE. The control group expressed less satisfaction with retrieval
      and demonstrated more errors when limiting. The test and control groups had the
      following average search scores respectively: 3.0 and 3.5 (pre-intervention), 3.3
      and 3.4 (post-intervention), and 2.0 and 3.8 (six-month post-intervention).
      CONCLUSION: Data suggest that measurable learning outcomes were achieved.
      Residents receiving instruction improved and retained searching skills six-months
      after intervention.

PMID- 11999178
TI  - Using a decade of data on medical student computer literacy for strategic
      planning.
AB  - PURPOSE: From 1991 through 2000, incoming medical students (M-Is) at the School
      of Medicine at Virginia Commonwealth University have been surveyed with a written
      questionnaire on their computer literacy. The survey's purpose is to learn the
      students' levels of knowledge, skill, and experience with computer technology to
      guide instructional services and facilities. METHODOLOGY: The questionnaire was
      administered during M-I orientation or mailed to students' homes after
      matriculation. It evolved from sixteen questions in 1991 to twenty-three
      questions in 2000, with fifteen questions common to all. RESULTS: The average
      survey response rate was 81% from an average of 177 students. Six major changes
      were introduced based on information collected from the surveys and advances in
      technology: production of CD-ROMs distributed to students containing required
      computer-based instructional programs, delivery of evaluation instruments to
      students via the Internet, modification of the lab to a mostly PC-based
      environment, development of an electronic curriculum Website, development of
      computerized examinations for medical students to prepare them for the
      computerized national board examinations, and initiation of a personal digital
      assistant (PDA) project for students to evaluate PDAs' usefulness in clinical
      settings. CONCLUSION: The computer literacy survey provides a snapshot of
      students' past and present use of technology and guidance for the development of
      services and facilities.

PMID- 11999179
TI  - Users' information-seeking behavior on a medical library Website.
AB  - The Central Medical Library (CMK) at the Faculty of Medicine, University of
      Ljubljana, Slovenia, started to build a library Website that included a guide to
      library services and resources in 1997. The evaluation of Website usage plays an
      important role in its maintenance and development. Analyzing and exploring
      regularities in the visitors' behavior can be used to enhance the quality and
      facilitate delivery of information services, identify visitors' interests, and
      improve the server's performance. The analysis of the CMK Website users'
      navigational behavior was carried out by analyzing the Web server log files.
      These files contained information on all user accesses to the Website and
      provided a great opportunity to learn more about the behavior of visitors to the
      Website. The majority of the available tools for Web log file analysis provide a
      predefined set of reports showing the access count and the transferred bytes
      grouped along several dimensions. In addition to the reports mentioned above, the
      authors wanted to be able to perform interactive exploration and ad hoc analysis
      and discover trends in a user-friendly way. Because of that, we developed our own
      solution for exploring and analyzing the Web logs based on data warehousing and
      online analytical processing technologies. The analytical solution we developed
      proved successful, so it may find further application in the field of Web log
      file analysis. We will apply the findings of the analysis to restructuring the
      CMK Website.

PMID- 11999180
TI  - Evidence-based medicine for consumers: a role for the Cochrane Collaboration.
AB  - Quality of health information on the Internet has been a concern since health
      information first began appearing on the Web. Evidence-based medicine tools,
      traditionally intended for physicians, may benefit consumers as they participate
      in making health care decisions. This article describes a rationale for Cochrane
      reviews as an evidence-based medicine tool for consumers. The Cochrane
      Collaboration, a global force for systematic literature reviews, has strict
      procedures for developing literature reviews. Criteria for Cochrane reviews are
      compared with critical evaluation skills commonly taught to consumers regarding
      the use of Websites. The Cochrane Collaboration's Consumer Network has
      established a separate Website, with review synopses written for an audience of
      consumers. Suggestions for further research into consumer use of the Cochrane
      Library and consumer involvement with the Cochrane Collaboration are discussed.

PMID- 11999181
TI  - How does the purchasing staff of an accident insurance organization seek
      information about treatment effectiveness?
AB  - OBJECTIVES: The objective is to study how the staff who purchase health care
      services for a large national government accident-compensation system seek
      information on treatment effectiveness, how they assess the quality of that
      information, whether they question the information sources they choose, and how
      familiar they are with the key concepts of evidence-based health care (EBHC).
      METHOD: Staff (22 out of 34) of the health purchasing division of the New Zealand
      Accident Compensation Corporation (NZ ACC) were interviewed using eight
      preformatted questions to which they could provide open and multiple answers.
      Responses were subsequently codified into typologies for quantitative analysis.
      RESULTS: Most respondents report that they assess the effectiveness of a
      treatment by accessing published information (nonhuman sources), by consulting
      others (human sources), or by both means. They assess the quality of information
      mostly by consulting others, and the second-highest proportion of responses state
      that they do not know how to evaluate the quality of information. No clear
      preference emerges with respect to the types of information needed to determine
      the effectiveness of treatments. The majority of the staff believes they can
      access information needed to determine treatment effectiveness through the
      Internet or information databases such as MEDLINE. Although most said they
      understand the key concepts of EBHC, only five out of twenty-two were able to
      accurately describe them. CONCLUSIONS: The findings suggest that there is a low
      level of awareness among the staff of the NZ ACC regarding the use of evidence
      and understanding of the key concepts of EBHC. Many surveyed staff members lack
      the skills or training to directly question information about effectiveness of a
      treatment. They have little idea of the information required to determine the
      effectiveness of a treatment, and the majority appears to lack the skills to
      evaluate the health care literature.

PMID- 11999182
TI  - Cost analysis of a project to digitize classic articles in neurosurgery.
AB  - In summer 2000, the Cushing/Whitney Medical Library at Yale University began a
      demonstration project to digitize classic articles in neurosurgery from the late
      1800s and early 1900s. The objective of the first phase of the project was to
      measure the time and costs involved in digitization, and those results are
      reported here. In the second phase, metadata will be added to the digitized
      articles, and the project will be publicized. Thirteen articles were scanned
      using optical character recognition (OCR) software, and the resulting text files
      were carefully proofread. Time for photocopying, scanning, and proofreading were
      recorded. This project achieved an average cost per item (total pages plus
      images) of $4.12, a figure at the high end of average costs found in other
      studies. This project experienced high costs for two reasons. First, the articles
      contained many images, which required extra processing. Second, the older fonts
      and the poor condition of many of these articles complicated the OCR process. The
      average article cost $84.46 to digitize. Although costs were high, the selection
      of historically important articles maximized the benefit gained from the
      investment in digitization.

PMID- 11999183
TI  - Print versus electronic journals: a preliminary investigation into the effect of
      journal format on research processes.
AB  - PURPOSE: To begin investigating the impact of electronic journals on research
      processes such as information seeking, the authors conducted a pilot journal-use
      study to test the hypothesis that patrons use print and electronic journals
      differently. METHODOLOGY: We placed fifteen high-use print titles also available
      in electronic format behind the circulation desk; patrons were asked to complete
      a survey upon requesting a journal. We also conducted a parallel survey of
      patrons using library computers. Both surveys asked patrons to identify
      themselves by user category and queried them about their journal use. RESULTS:
      During the month-long study, patrons completed sixty-nine surveys of electronic
      and ninety surveys of print journal use. Results analysis indicated that fellows,
      students, and residents preferred electronic journals, and faculty preferred
      print journals. Patrons used print journals for reading articles and scanning
      contents; they employed electronic journals for printing articles and checking
      references. Users considered electronic journals easier to access and search than
      print journals; however, they reported that print journals had higher quality
      text and figures. DISCUSSION/CONCLUSION: This study is an introductory step in
      examining how electronic journals affect research processes. Our data revealed
      that there were distinct preferences in format among categories. In addition to
      collection management implications for libraries, these data also have
      implications for publishers and educators; current electronic formats do not
      facilitate all types of uses and thus may be changing learning patterns as well.

PMID- 11999184
TI  - Distribution of medical school course materials through the web: addressing the
      issue of printing through an analysis of the costs and utilization.

PMID- 11999185
TI  - La Biblioteca Medica Nacional: The National Medical Library of Cuba.

PMID- 11999186
TI  - CISMeF-patient: a French counterpart to MEDLINEplus.

PMID- 11999187
TI  - Multiple database coverage of structural biology.

PMID- 11999188
TI  - Artificial skin: past, present and future.
AB  - The integrity of the skin should be restored as soon as possible whenever the
      skin gets wounded. Recent research has revealed some of the complex pathways in
      wound healing. Based on this knowledge, researchers have been looking for better
      skin substitutes to treat difficultly healing or large wounds. Some of these
      highly sophisticated wound dressings, also known as bio-dressings, contain
      material of human or animal origin, e.g. cultured skin cells. Although the ideal
      skin substitute has not been established yet, the currently available bio
      dressings help clinicians close difficultly healing skin wounds.

PMID- 11999189
TI  - Novel perspectives on hepatitis B vaccine in dialysis population.

PMID- 11999190
TI  - Recent developments on human cell lines for the bioartificial liver.
AB  - Most bioartificial liver (BAL) devices contain porcine primary hepatocytes as
      their biological component. However, alternatives are needed due to
      xenotransplantation associated risks. Human liver cell lines have excellent
      growth characteristics and are therefore candidates for application in BAL
      devices. Tumour-derived cell lines HepG2 and C3A express a variety of liver
      functions, but some specific liver functions, like ammonia detoxification and
      ureagenesis are insufficient. Immortalised human hepatocytes might offer better
      prospects. The balance between immortalisation and transformation with
      dedifferentiation of cells seems controllable by conditional immortalisation
      and/or the use of telomerase as immortalising agent. Another promising approach
      will be the use of embryonic or adult human stem cells. Rodent stem cells have
      been directed to hepatic differentiation in vitro, which might be applicable to
      human stem cells. However, both functionality and safety of immortalised human
      liver cell lines and differentiated stem cells should be improved before
      successful use in BAL devices becomes reality.

PMID- 11999191
TI  - Early experiences with a porcine hepatocyte-based bioartificial liver in acute
      hepatic failure patients.
AB  - Orthotopic liver transplantation (OLT) is the only effective therapeutic modality
      in severe acute hepatic failure (AHF). The scarcity of organs for transplantation
      leads to an urgent necessity for temporary liver support treatments in AHF
      patients. A hepatocyte-based bioartificial liver (BAL) is under investigation
      with the main purpose to serve as bridging treatment until a liver becomes
      available for OLT, or to promote spontaneous liver regeneration. We developed a
      novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte
      culture and an integrated pumping apparatus in which, after plasmapheresis, the
      patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred
      thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for
      clinical liver support treatment. The BAL system was used 8 times in supporting 7
      AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients
      with no history of previous liver diseases were affected by fulminant hepatic
      failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the
      transplanted liver, and one by AHF due to previous abdominal trauma and liver
      surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which
      lasted 6-24 hours. All patients tolerated the procedures well, as shown by an
      improvement in the level of encephalopathy, a decrease in serum ammonia,
      transaminases and an amelioration of the prothrombin time, with full neurological
      recovery after OLT Our initial clinical experience confirms the safety of this
      BAL configuration and suggests its clinical efficacy as a temporary liver support
      system in AHF patients.

PMID- 11999192
TI  - Albumin loss in on-line hemodiafiltration.
AB  - BACKGROUND: Based on the increased hydraulic permeability of the new high
      permeability polyethersulfone membrane, DIAPES HF-800, we investigated the
      kinetics and handling of albumin in high volume on-line hemodiafiltration (HDF).
      METHODS: Seven patients on predilutional HDF were studied in two consecutive
      sessions. Blood flow rate and transmembrane pressure were continuously monitored.
      Spent dialysate was spilled at 20 ml/h every hour. Albumin was measured in blood
      and dialysate by immunonephelometry. Albumin and proteins adsorbed onto the
      dialyzer membrane were eluted after treatment with Triton X. Ultrafiltrates
      collected at 1 and 2 hours of treatment were pooled from different patients and
      incubated for 24 hours at 37 degrees C with bovine serum albumin (BSA). Total
      sulphydryl groups were evaluated using Ellmann's reagent [5, 5'-dithio-bis(2
      nitrobenzoic acid)]. RESULTS: In all 7 patients, the total loss of albumin was
      3.99 +/- 1.81 g, ranging between 1.09 and 6.82 g/session. Most albumin loss
      occurred in the first 60 min of pre-dilutional hemodiafiltration (1.92+0.83 g).
      There was no correlation between transmembrane pressure, urea clearance and the
      loss of albumin. Plasma water urea clearance values were stable over the
      treatment (234 +/- 14.3 ml/min). Plasma albumin concentration did not decrease
      during HDF sessions. Albumin adsorbed onto the dialyzers was 0.7 +/- 1.6 mg but
      the total amount of adsorbed proteins was much higher (130 + 90 mg). In addition,
      the ultrafiltrate collected during HDF sessions was able to induce oxidation of
      bovine serum albumin as measured by total protein sulfhydryl groups: bovine serum
      albumin incubated in the presence of ultrafiltrate collected at 1 hour had a
      sulfhydryl loss of 56.3 +/- 5.7% (p < 0.0001 vs control), and bovine serum
      albumin incubated with ultrafiltrate collected at 2 hours had a loss of 67.5 +/-
      3.8% (p < 0.003 vs control). CONCLUSION: The present study shows the high inter-
      and intra-patient variability of transmembrane passage of albumin in chronically
      uremic patients undergoing pre-dilutional HDF. Factors involved do not seem to be
      correlated to transmembrane pressure but rather to an interaction with the
      polymer surface. Albumin adsorption was minimal and was significantly lower than
      that of other plasma proteins. Albumin loss during HDF seemed to have no acute
      impact on plasma albumin. In addition, we demonstrated the presence of
      prooxidative compounds able to oxidize albumin, of which extracorporeal removal
      by HDF procedure could be beneficial for HD patients.

PMID- 11999193
TI  - In vitro evaluation of the hydraulic permeability of polysulfone dialysers.
AB  - An in vitro set-up has been designed to study the hydraulic permeability of
      hollow fiber dialysers. Forward and reverse dialysate ultrafiltration were
      determined using both sterile dialysers and samples with a protein layer settled
      on the membrane (Fresenius F6, F8, F60 and F80). The ultrafiltration coefficient
      KUF (ml/h.mmHg) was calculated as the ratio of volumetrical flow (QUF) and
      transmembrane pressure (TMP) measurements. The protein layer on the membrane was
      induced either by recirculating human plasma through the dialysers (in vitro) or
      by a standard hemodialysis session (in vivo). KUF is largely independent of TMP
      up to 600mmHg (low flux) and 60mmHg (high flux) for forward and reverse flow In
      sterile dialysers, backfiltration yields a significantly different KUF except for
      the F80. An in vitro induced protein layer on the membrane decreases KUF15-30%
      (forward) and 4-12% (backward) in low flux and 45-70% (forward) and 65-73%
      (backward) in high flux dialysers.

PMID- 11999194
TI  - Reversibility of artifacts of fluid volume measurements by bioimpedance caused by
      position changes during dialysis.
AB  - The effect of temporary position changes, sitting up from supine, on
      extracellular (ECW) and intracellular (ICW) resistances and fluid volumes
      calculated from whole body bioimpedance using a Xitron 4200 impedancemeter was
      investigated on 8 patients during dialysis for a total of 11 tests. It was found
      that ECW resistance decreased instantaneously by an average of 2.3% when the
      patient sits up, due to plasma and interstitial fluid shift into the legs which
      decreases leg resistance, the major contributor to total resistance. This drop in
      resistance is incorrectly interpreted by the device as an increase in ECW volume
      which averages 235 ml. But this effect is completely reversible and both ECW
      resistance and fluid volume rapidly resume their normal course when the patient
      returns to his initial position. No significant variation in ICW resistance was
      observed in any of the patients at the position change. We conclude that
      segmental impedance, which has been proposed to minimize this artifact, is not
      advisable in dialysis monitoring and that it is simpler to ignore or switch off
      measurements during the position change so that later data are not affected by
      it.

PMID- 11999195
TI  - Poly2-methoxyethylacrylate (PMEA) coated oxygenator: an ex vivo study.
AB  - PMEA is a hydrophilic polymer coating with a unique design that minimizes the
      adsorption and denaturation of proteins and blood cells. This study compares
      thrombus resistance, blood path resistance, thrombocyte profile, and blood trauma
      of the PMEA coated Capiox membrane oxygenator (Terumo, Japan) vs. an uncoated
      version. METHOD: Six calves (mean bodyweight: 75.3 +/- 4.5kg) were placed on
      cardiopulmonary bypass for 6 hours and randomly assigned to the coated or
      uncoated oxygenator, with a low heparinisation protocol (ACT > 180s). RESULTS:
      Macroscopically, red staining was observed in all uncoated oxygenators, and in
      none of the coated ones. Inlet pressure was significantly higher in the uncoated
      group (at 1 h: 279 +/- 25 vs. 175 +/- 11mmHg, p < 0.01 and at 6h: 217 +/- 10 vs.
      171(8mmHg, p < 0.01). Thrombocyte count values (corrected for hematocrit and
      normalized by prebypass values) were significantly higher in the coated group (at
      1 h: 76 +/- 6 vs. 53 +/- 13%, p < 0.01 and at 6 h: 70 +/- 6 vs. 44 +/- 26%, p <
      0.01). Plasma hemoglobin was below 100mg/L in both groups throughout the
      experiments. CONCLUSIONS: When compared with uncoated oxygenator, PMEA coated
      oxygenator exhibited increased thrombus resistance with lower inlet pressure and
      lower thrombocyte consumption. In both groups, trauma to red cells was minimal,
      emphasizing the efficient design of this type of oxygenator.

PMID- 11999196
TI  - Evaluation of peripheral nerve regeneration across an 80-mm gap using a
      polyglycolic acid (PGA)--collagen nerve conduit filled with laminin-soaked
      collagen sponge in dogs.
AB  - We evaluated peripheral nerve regeneration using a novel artificial nerve
      conduit. The conduit was made of a polyglycolic acid(PGA) - collagen tube filled
      with laminin- soaked collagen sponge. We implanted this nerve conduit across an
      80mm gap in the peroneal nerve of dogs. Histological observation 12 months after
      implantation showed numerous unmyelinated and myelinated nerve fibershad
      regenerated beyond the gap. Neurofilaments were widely observed
      immunohistochemically in the regenerated nerve segments. These findings indicated
      that newly regenerated axons had extended across the gap and connected into the
      distal nerve segments. Compound muscle action potentials(CMAPs) and somatosensory
      evoked potentials (SEPs) were recorded in all dogs. At 12 months, the CMAPs
      indicated complete recovery, while the SEPs showed incomplete but substantial
      recovery. Walking patterns had returned to near-normal 12 months after
      implantation. Use of this nerve conduit can lead to peripheral nerve elongation
      and favorable functional recovery across a wider nerve gap.

PMID- 11999197
TI  - The Aachen-keratoprosthesis--a flexible KPro that permits intraocular pressure
      measurement.
AB  - PURPOSE: Postoperative glaucoma is one of the major complications observed in
      patients with keratoprostheses (KPro). The optical components of the majority of
      KPros are rigid and inflexible, which prevents indirect tonometry by common
      methods. This study confirms that the Aachen-KPro allows measurements of
      intraocular pressure (IOP) due to its flexible optical part with a modified
      Schiotz tonometer. METHODS: The Aachen-KPro was placed in a special chamber where
      pressure can be generated and monitored by a transducer. Measurements were taken
      by common ophthalmologic methods. The results were compared to the initial
      pressure values in the chamber. RESULTS: With the Goldmann tonometer, the Tono
      Pen and the topography system (Technomed), no significant pressure changes could
      be observed. The results of the Schiotz tonometer were promising. It was slightly
      modified and standard curves with different weights could be obtained.
      CONCLUSIONS: With a modified Schiotz tonometer, it is possible to detect elevated
      IOPs. Modifying this common instrument is inexpensive and can be easily
      performed. This advantage of the Aachen-KPro permits early management of
      postoperative high tension glaucoma.

PMID- 11999198
TI  - The epochs and ethics of incontinence surgery: is the direction forward or
      backwards?

PMID- 11999199
TI  - Urinary incontinence in elite female athletes and dancers.
AB  - The aim of this study was, to determine the frequency of urinary loss in elite
      women athletes and dancers. Elite athletes in eight different sports, including
      ballet, filled in an evaluated questionnaire about urinary incontinence while
      participating in their sport/dancing and during daily life activities. A total of
      291 women with a mean age of 22.8 years completed the questionnaire, providing a
      response rate of 73.9%. Overall, 151 women (51.9%) had experienced urine loss,
      125 (43%) while participating in their sport and 123 (42%) during daily life. The
      proportion of urinary leakage in the different sports was: gymnastics 56%, ballet
      43%, aerobics 40%, badminton 31%, volleyball 30%, athletics 25%, handball 21% and
      basketball 17%. During sport 44% had experienced leakage a few times, 46.4% now
      and then, and 9.6% frequently. During daily life the figures were: 61.7% a few
      times, 37.4% now and then, and 0.8% frequently. Of those who leaked during sport,
      95.2% experienced urine loss while training versus only 51.2% during competition
      (P<0.001). The activity most likely to provoke leakage was jumping. Sixty per
      cent (91/151) occasionally wore pads or panty shields because of urine loss.
      Urinary leakage is common among elite athletes and dancers, particularly during
      training, but also during daily life activities.

PMID- 11999200
TI  - Incidence, risk factors and morbidity of unintended bladder or ureter injury
      during hysterectomy.
AB  - To determine the incidence, risk factors and morbidity of unintended operative
      injury to the bladder or ureter during hysterectomy, a retrospective case-control
      study of women with these injuries from 1 January 1993 to 1 January 1998 was
      performed. The incidence of bladder and ureter injury, respectively, was 0.58%
      and 0.35% for abdominal hysterectomy, 1.86% and 0% for vaginal hysterectomy, and
      5.13% and 1.71% for hysterectomies performed for obstetric indications. Women
      with injury during abdominal hysterectomy were found to have greater blood loss,
      longer operative times, longer postoperative stays, more febrile morbidity, and
      more frequent transfusions. Similar trends were seen for other hysterectomy
      types. The incidence of operative bladder or ureter injury is relatively low.
      However, even when recognized, these individuals experience greater operative and
      postoperative morbidity. This highlights the importance of surgical technique
      directed toward minimization of these injuries, and careful intra- and
      postoperative surveillance aimed at early detection.

PMID- 11999201
TI  - Cystodefecoperitoneography in patients with genital prolapse.
AB  - The aim of the study was to prospectively evaluate pre- and postoperative
      findings of cystodefecoperitoneography (CDP) and to correlate the findings to the
      clinical examination in patients with genital prolapse. Twenty-five female
      patients were investigated both pre- and postoperatively with a standardized
      questionnaire, clinical examination and CDP, including contrast medium in the
      rectum, vagina, bladder, small bowel and peritoneal cavity. At preoperative
      clinical examination a rectocele was diagnosed in 24 patients, a cystocele in 7
      and an enterocele in 2. At the preoperative CDP a rectocele was diagnosed in 21
      patients, a cystocele in 22 patients and a peritoneocele in 9, of which six
      contained small bowel (i.e. an enterocele). Surgery was performed according to
      the clinical findings. At the postoperative clinical examination no rectocele was
      diagnosed, a cystocele was diagnosed in 3 patients and an enterocele in 1.
      Postoperative CDP showed a rectocele in 4 patients, a cystocele in 24 and a
      peritoneocele in 7 patients, of which three contained small bowel (i.e. an
      enterocele). CDP may complement the clinical assessment of patients with genital
      prolapse, in particular to confirm or detect defects involving the posterior
      compartment. The radiologic definition of cystocele needs further evaluation.

PMID- 11999202
TI  - Intrinsic sphincter deficiency: do the maximum urethral closure pressure and the
      Valsalva leak-point pressure identify different pathogenic mechanisms?
AB  - A prospective analysis of 166 women with genuine stress incontinence was
      performed comparing Valsalva leak-point pressure (VLPP) and maximum urethral
      closure pressure (MUCP) with age, previous urogynecologic surgery and/or
      hysterectomy, poor urethral mobility, weight, menopause and vaginal deliveries,
      to find correlations with intrinsic sphincter deficiency (ISD). Cut-off value for
      VLPP were 60 cmH2O and for MUCP 30 cmH2O. MUCP < or = 30 cmH2O identifies a group
      of patients with more severe incontinence, a shorter urethral functional length
      (UFL) (P = 0.02), more previous urogynecologic operations and the menopause (P =
      0.004 and P = 0.000), and older age (P = 0.000). VLPP < or = 60 cmH2O identifies
      a group of patients with more severe incontinence, a shorter UFL (P = 0.005),
      more previous urogynecologic surgery (P=0.006) and poorer urethral mobility (P =
      0.004). As these two tests measure different components of urethral functions we
      can hypothesize that they detect different pathogenic processes contributing to
      ISD. When one or both tests is abnormal incontinence is more severe and the
      incidence of poor prognostic factors is increased.

PMID- 11999203
TI  - Comparison of anterior colporrhaphy versus Bologna procedure in women with
      genuine stress incontinence.
AB  - The aim of the study was to compare the anterior colporrhaphy and the Bologna
      operation for the treatment of anterior vaginal wall prolapse associated with
      genuine urinary incontinence (GSI). Sixty-two women undergoing surgery for GSI
      and concurrent grade 2-3 cystocele were the subjects of the study. Anterior
      colporraphy was performed on 31 women (group A) and the Bologna operation on
      another 31 (group B). The mean follow-up was 3 years (range 2-7). Perioperative
      complications, including urinary tract infections, occurred in 16% of group A
      versus 42% of group B (P<0.001). Anatomic success regarding the prolapse was,
      respectively, 92.9% (26/28) and 84.6% (22/26) (P = 0.25). Subjective cure rates
      of GSI (patient history) were 57.1% in group A (16/28) and 87% in group B (23/26)
      (P<0.05). Objective cure rates of GSI (negative stress test result) were 53.6% in
      group A (15/28) and 84.6% in group B (22/26) (P<0.02). We concluded that the
      Bologna operation was more effective for treating GSI associated with anterior
      vaginal prolapse than was anterior colporraphy, with an increased rate of
      morbidity and postoperative urinary retention.

PMID- 11999204
TI  - Posterior intravaginal slingplasty (infracoccygeal sacropexy) for severe
      posthysterectomy vaginal vault prolapse--a preliminary report on efficacy and
      safety.
AB  - The infracoccygeal sacropexy, or posterior intravaginal slingplasty, was first
      reported by Petros as a minimally invasive procedure for the treatment of vault
      prolapse. This report is a prospective observational study that confirms the
      efficacy and safety of this new procedure. In this operation the IVS Tunneller
      (Tyco Healthcare, USA) is used to insert an 8 mm polypropylene tape between the
      perineum and the vaginal vault. The resulting artificial neoligament reinforces
      the atrophied uterosacral ligaments. The rectovaginal fascia and perineal body
      are then repaired by a technique that includes using a bridge of vaginal
      epithelium to strengthen the central vaginal epithelium at the point of maximum
      weakness. The symptomatic cure rates for prolapse were 91%, urgency 79%, nocturia
      82% and pelvic pain 78%. All patients were discharged home within 24 hours. There
      were minimal surgical complications and no transfusions were required. The
      technique is safe, minimally invasive, has a short learning curve, and the skills
      needed are those of any competent pelvic surgeon.

PMID- 11999205
TI  - Does weight loss improve incontinence in moderately obese women?
AB  - The aim of this study was to evaluate the effect of weight reduction on urinary
      incontinence in moderately obese women. This prospective cohort study enrolled
      moderately obese women experiencing four or more incontinence episodes per week.
      BMI and a 7-day urinary diary were collected at baseline and on the completion of
      weight reduction. The study included 10 women with a mean (+/-SD) baseline BMI of
      38.3 (+/-10.1) kg/m2 and 13 (+/-10) incontinent episodes per week. Participants
      had a mean BMI reduction of 5.3 (+/-6.2) kg/ m2 (P < 0.03). Among women achieving
      a weight loss of > or = 5%, 6/6 had > or = 50% reduction in incontinence
      frequency compared to 1 in 4 women with < 5% weight loss (P < 0.03). Incontinence
      episodes decreased to 8 (+/-10) per week following weight reduction (P < 0.07).
      The study demonstrated an association between weight reduction and improved
      urinary incontinence. Weight reduction should be considered for moderately obese
      women as part of non-surgical therapy for incontinence.

PMID- 11999206
TI  - Levatorplasty release and reconstruction of rectovaginal septum using allogenic
      dermal graft.
AB  - The goal of reconstructive vaginal surgery include: restoration of normal
      anatomy, as well as maintaining visceral and sexual function. Rectocele repair
      can be performed utilizing a number of techniques, however some of these
      techniques severely distort the posterior vaginal wall anatomy and subsequently
      may result in dyspareunia. We report two patients with postoperative dyspareunia
      following levatorplasty technique for the treatment of rectocele. The patients
      elected to have their levatorplasty released and their rectovaginal septum
      reconstructed utilizing allogenic dermal graft. Postoperatively both patients are
      sexually active without evidence of dyspareunia or rectocele.

PMID- 11999207
TI  - Mesonephroid adenocarcinoma of the bladder and urethra: a case report.
AB  - Mesonephric or mesonephroid adenocarcinoma of the bladder may be a malignant form
      of nephrogenic adenoma or nephroid metaplasia. The lesion is rare, and to the
      best of our knowledge only 9 cases have been reported in the world literature. We
      report another case of mesonephroid adenocarcinoma of the bladder and urethra
      which was treated with transurethral resection and subsequent chemotherapy.

PMID- 11999208
TI  - An unusual complication of vesical stones.
AB  - The author reports a complicated recurrence of genital tract fistula. The initial
      vesicovaginal fistula resulted from obstructed labor, which was subsequently
      surgically managed without success. The patient had a recurrent vesicovaginal
      fistula that was formed by the erosion of vesical stones through the anterior
      endopelvic fascia into the vagina. The stones eventually eroded into the rectum,
      resulting in the formation of a complex vesicovaginal and rectovaginal fistula.

PMID- 11999209
TI  - Persistence of delayed hypersensitivity following transurethral collagen
      injection for recurrent urinary stress incontinence.
AB  - Transurethral collagen injection is both safe and effective when used for the
      treatment of genuine stress urinary incontinence. It is associated with a minimal
      inflammatory response, and virtually no foreign body reaction. Most allergic
      reactions occur within 72 hours of treatment (immediate hypersensitivity).
      Although uncommon, delayed hypersensitivity reactions may occur and it is
      advisable to administer a collagen skin test 30 days prior to the procedure.
      Adverse effects may cause long-term sequelae, such as severe trigonal tenderness,
      urgency, frequency, hematuria, urinary retention and persistent stress urinary
      incontinence. A case of a prolonged delayed hypersensitivity reaction following
      negative collagen skin testing after transurethral collagen injection is
      presented. Treatment of stress incontinence could not be initiated until symptoms
      decreased significantly after 1 year.

PMID- 11999210
TI  - Botulinum toxin urethral sphincter injection resolves urinary retention after
      pubovaginal sling operation.
AB  - The management of prolonged urinary retention following pubovaginal sling surgery
      typically involves transvaginal urethrolysis for anatomical urethral obstruction.
      Brubaker recently reported on urethral sphincter abnormalities as a cause of
      postoperative urinary retention following either Burch suspension or a
      pubovaginal sling procedure. We report a case of functional urethral obstruction
      and detrusor acontractility following pubovaginal sling surgery that was
      successfully treated by botulinum A toxin urethral sphincter injection.

PMID- 11999211
TI  - Predictive value of clinical evaluation of stress urinary incontinence: a summary
      of the published literature.

PMID- 11999212
TI  - Zilbert AW, Farrell SA. External iliac artery laceration during tension-free
      vaginal tape procedure. Int Urogynecol J 2001; 12:141-143.

PMID- 11999213
TI  - The effect of patient position on leak-point pressure measurements in women with
      genuine stress incontinence.
AB  - The aim of this study was to determine the quantitative and qualitative effects
      of patient position on coughing and Valsalva leak-point pressure in women with
      genunie stress incontinence. Thirty-seven patients with genuine stress
      incontinence and 4 with mixed incontinence underwent multichannel urodynamics
      using a standardized protocol. Leak-point pressures were performed using 8 Fr
      microtip catheters placed in the bladder and vagina at a bladder volume of 250 ml
      in the supine, semirecumbent and standing positions. Urethral pressure
      profilometry was performed in the semirecumbent position at a bladder volume of
      250 ml. The mean (range) age, and median (range) gravidity, parity, body mass
      index (BMI), and mean (range) Q-tip deflection angle were 61 years (36-80), 3 (1
      8), 3 (1-6), 26 (22-30) and 55.8 degrees (25 degrees-80 degrees), respectively.
      The mean (+/- standard deviation) Valsalva leak-point pressures in the supine,
      semirecumbent and standing positions were 82 +/- 23, 73 +/- 24 and 63 +/- 22
      cmH2O, respectively (P<0.001). The mean (+/- standard deviation) cough leak-point
      pressures also decreased as the patients were moved from the supine (98 +/- 29
      cmH2O) to the semirecumbent (88 +/- 24 cmH2O) and standing positions (77 +/- 24
      cmH2O) (P<0.001). The correlation between leak-point pressure and maximum
      urethral closure pressure was statistically significant and was dependent upon
      patient position and the provocative maneuver used.

PMID- 11999214
TI  - The EGF/ErbB receptor family and apoptosis.
AB  - The ErbB receptor family can activate a multitude of cell signaling pathways that
      involve many aspects of cellular function. The four members of the ErbB receptor
      family interact with diverse ligands and substrates, as well as with each other
      through cell surface heterodimerization. The sum of these diverse interactions is
      a signaling network that is complex but also finely regulated. Among the cellular
      functions influenced by ErbB signaling is cell survival. ErbB receptor signaling
      has been demonstrated to interact with all of the major mechanisms of cell death
      signaling in a manner that promotes cell survival. Survival factors such as Ras,
      PI3-K, Akt, and Bcl-x/-2 all have been shown to be activated by ErbB signaling
      (Fig. 5). ErbB abrogation of apoptotic signals has been shown to play an
      important role during embryonic tissue development, in normal adult tissue
      maintenance (e.g. mammary tissue, wound healing), and also in tumor development
      and progression. Although the majority of studies suggest that ErbB receptor
      family members are mediators of cell survival, there have been occasional reports
      suggesting that ErbB receptors can induce cell death under selected experimental
      conditions. While this apparent discrepancy remains unresolved, in many of these
      reports, cell death may be the result of anoikis in response to changes in the
      cytoskeleton associated with hyperstimulation of ErbB signaling. The notion that
      ErbB receptor family members function to promote cell survival is not a recent
      observation. However, how this family functions to prevent apoptosis is an area
      that only recently has been considered. The understanding of ErbB receptor
      signaling as it relates to the avoidance of apoptosis had profound implications
      for the treatment of solid tumors originating in multiple tissues, as well as for
      the treatment of neurodegenerative disease. Further elucidation of the complex
      relationships between ErbB receptor signaling networks and the apoptotic
      machinery is certain to yield biologically important and potentially life-saving
      information.

PMID- 11999215
TI  - Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on
      intestinal absorption of 3-O-methyl-D-glucose are less pronounced than gut
      mucosal growth responses.
AB  - The relationship between insulin-like growth factor-I (IGF-I) peptide-induced
      increases in bowel mass and functional improvement is unclear. We utilised three
      independent methods to investigate the effects of IGF-I peptides on intestinal
      absorption of the glucose analogue, 3-O-methyl-D-glucose (3MG) in rats. Rats
      received vehicle, IGF-I or the more potent analogue, long-R3-IGF-I via
      subcutaneously implanted mini-pump, for 7 days, at which time intestinal
      absorption was assessed by: (1) plasma 3MG appearance following oral gavage, (2)
      single-pass- or (3) recirculating-perfusion of a jejunal segment. 3MG (320 or 800
      mg) was gavaged on day 7 to rats treated with vehicle, IGR-I or long-R3-IGF-I.
      With the lower 3MG dose, only long-R3-IGF-I increased (40%) the initial rate of
      3MG appearance in plasma. IGF-I had no significant effect, whilst at the higher
      3MG dose neither peptide was effective. Utilising perfusion techniques, long-R3
      IGF-I, but not IGF-I, significantly increased 3MG uptake per cm of jejunum by up
      to 69%, although significance was lost when expressed as a function of tissue
      weight. Long-R3-IGF-I, but not native IGF-I, enhanced 3MG absorption from the
      intestinal lumen, presumably reflecting an increased mucosal mass rather than an
      up-regulation of specific epithelial glucose transporters.

PMID- 11999216
TI  - Influence of platelet-derived growth factor on lens epithelial cell proliferation
      and differentiation.
AB  - The expression pattern of platelet-derived growth factor (PDGF) and its receptor
      suggest a role in lens cell proliferation. PDGF is strongly expressed in the iris
      and ciliary body, situated opposite the proliferative cells of the lens
      epithelium which express the PDGF-alpha receptor. In this study, using lens
      epithelial explant cultures, we report that PDGF can induce a dose and time
      dependent increase in lens cell DNA synthesis. Culturing lens explants with both
      PDGF and FGF (a mitogen and differentiation factor for lens cells) resulted in
      responses greater than those induced by either growth factor alone. PDGF did not
      induce any changes typical of fibre differentiation; however, in combination with
      FGF it potentiated the fibre differentiating activity of FGF. Results obtained in
      this study support previous indications that PDGF has an important role in
      regulating lens cell proliferation. In addition, PDGF may have a role in
      potentiating FGF-induced lens fibre differentiation in vivo.

PMID- 11999217
TI  - Hierarchy of stroma-derived factors in supporting growth of stroma-dependent
      hemopoietic cells: membrane-bound SCF is sufficient to confer stroma competence
      to epithelial cells.
AB  - Hemopoiesis takes place in a microenvironment where hemopoietic cells are closely
      associated with stroma by various interactions. Stroma coregulates the
      proliferation and differentiation of hemopoietic cells. Stroma-hemopoietic-cell
      contact can be supported by locally produced membrane associated growth factors.
      The stroma derived growth factor, stem cell factor (SCF) is important in
      hemopoiesis. We examined the different biological interactions of membrane bound
      and soluble SCF with human hemopoietic cells expressing the SCF receptor, c-kit.
      To analyze the function of the SCF isoforms in inducing the proliferation of
      hemopoietic TF1 or Cord blood (CB) CD34+ cells we used stroma cell lines that
      differ in their presentation of no SCF, membrane SCF, or soluble SCF. We
      established a new coculture system using an epithelial cell line that excludes
      potential interfering effects with other known stroma encoded hemopoietic growth
      factors. We show that soluble SCF, in absence of membrane-bound SCF, inhibits
      long term clonal growth of primary or established CD34+ hemopoietic cells,
      whereas membrane-inserted SCF "dominantly" induces long term proliferation of
      these cells. We demonstrate a hierarchy of these SCF isoforms in the interaction
      of stroma with hemopoietic TF1 cells. Membrane-bound SCF is "dominant" over
      soluble SCF, whereas soluble SCF acts epistatically in interacting with
      hemopoietic cells compared with other stroma derived factors present in SCF
      deficient stroma. A hierarchy of stroma cell lines can be arranged according to
      their presentation of membrane SCF or soluble SCF. In our model system, membrane
      bound SCF expression is sufficient to confer stroma properties to an epithelial
      cell line but soluble SCF does not.

PMID- 11999218
TI  - Expression of pleiotrophin in hepatic nonparenchymal cells and preneoplastic
      nodules in carbon tetrachloride-induced fibrotic rat liver.
AB  - Pleiotrophin (PTN) is a heparin-binding protein, which induces growth,
      angiogenesis, differentiation, and transformation of cells. The aim of this study
      was to examine the role of PTN in liver fibrogenesis. Rats were treated with
      carbon tetrachloride (CCl4) for 3-9 weeks to induce liver fibrosis. The sirius
      red staining of these liver tissue sections clearly showed the development of
      fibrosis and glutathione S-transferase placental type-positive preneoplastic
      nodules emerged at 7 weeks of the treatment. PTN expression was investigated in
      fibrotic liver tissues at the mRNA level using a real-time reverse transcription
      polymerase chain reaction and at the protein level by immunohistochemistry.
      Quantity of PTN mRNA increased 5-fold in fibrotic liver tissues at 7 weeks of
      CCl4-treatment over the control values. Immunohistochemistry localized PTN
      protein on hepatic nonparenchymal cells, mostly stellate cells and some of
      Kupffer cells, and the preneoplastic nodules in fibrotic liver tissues. PTN mRNA
      expression is significantly upregulated in the CCl4-induced chronic rat fibrotic
      liver tissues. We suggest that PTN might be involved in fibrogenesis and
      preneoplastic changes of liver.

PMID- 11999219
TI  - The comparability of resource utilisation for Europeans and non-Europeans
      following stroke in New Zealand.
AB  - AIMS: We sought to explore resource use both in hospital and the community twelve
      months after hospital discharge for patients of different ethnicity admitted to
      hospital with acute stroke. METHODS: Resource utilisation data were collected for
      consecutive patients admitted to each of three general hospitals in the
      Wellington region over a nine month period. Patients were interviewed, where
      possible, at three, six and twelve months after hospital discharge. Ethnicity was
      determined by self report. RESULTS: Non-Europeans had longer hospital stays than
      Europeans (median 36 days vs 18 days, p = 0.01). Contact with rehabilitation
      professionals in the community was low for all groups with no significant
      differences between Europeans and non-Europeans. For the entire cohort, spending
      on institutional care was around ten times higher than spending on community
      rehabilitation in the first twelve months following stroke. CONCLUSIONS:
      Differences in hospital stay after stroke may reflect problems of access to
      inpatient rehabilitation services for younger people and not relate directly to
      the ethnicity of the patient. With the projected increasing proportion of Maori
      and Pacific people in the population, combined with the aging of that population,
      health policy-makers need to consider the implications of differences in resource
      utilisation for different ethnic groups in New Zealand. How to manage all the
      available resources for people with stroke to maximise outcome remains an
      important issue for health funders.

PMID- 11999220
TI  - Observations of summer sun protection among children in New Zealand: 1998-2000.
AB  - AIMS: To examine sun protection among New Zealand children (ten years and under)
      at beaches and playgrounds. METHODS: In the summers of 1998, 1999 and 2000,
      observations were made of 753 children at selected beaches and playgrounds in
      Dunedin and Hawkes Bay to determine the extent of sun protection. Parents/carers
      were also interviewed about sun protection. RESULTS: Across most body sites,
      levels of protection were high. Clothing and SPF15+ sunscreen were used most
      often, while the use of shade was relatively low. About four in every ten
      parents/caregivers were aware of the UV index or burn-time. Level of sun
      protection among children at beaches was best predicted by parent/carer's own
      level of protection, the child's perceived susceptibility to burning, and being a
      preschooler. CONCLUSIONS: Observed levels of sun protection among the children
      were high and most likely reflected an increased awareness among parents and
      carers of the social acceptability of protective behaviours. Nevertheless,
      opportunities to seek shade were limited, and the provision of shade at beaches
      and playgrounds represents an important next step in a community wide approach to
      sun protection.

PMID- 11999221
TI  - Awareness, knowledge and attitudes of lead maternity carers towards early-onset
      neonatal group B streptococcal disease.
AB  - AIM: To determine awareness, knowledge and attitudes of lead maternity carers
      (LMCs) towards early-onset neonatal group B streptococcus (GBS) infection and its
      prevention. METHODS: An anonymous, self-administered questionnaire was sent to
      the 155 practising LMCs in Wellington and Hutt Valley. RESULTS: Completed
      questionnaires were returned by 84 (54%) LMCs (59 midwives). 66 (79%) believed
      perinatal GBS infections were important, 70 (85%) supported antenatal screening,
      while 68 (81%) were confident of determining risk factors for GBS infection and
      counselling women. However, less than one-third nominated major risk factors,
      none identified all five high-risk criteria and only 22 (26%) regularly discussed
      GBS with clients. When asked to name high-risk criteria, midwives were more
      likely than doctors to disclose they had incomplete knowledge or not to answer
      this item (53% vs 20%; p < 0.006). Of the 48 (57%) LMCs routinely employing GBS
      prevention strategies, 34 (71%) used culture-based screening, relying mainly upon
      high-vaginal swabs from the first-trimester. CONCLUSIONS: Despite widespread
      awareness of perinatal GBS disease, only 57% of surveyed LMCs practised
      prevention strategies and none completely followed published recommendations. A
      New Zealand consensus or improved dissemination of local guidelines is required
      to achieve further reductions in neonatal GBS sepsis.

PMID- 11999222
TI  - Vibrio vulnificus necrotising fasciitis and septicaemia.

PMID- 11999223
TI  - Socio-economic position is more than just NZDep.

PMID- 11999224
TI  - How much excercise is enough? Are we sending the right message?

PMID- 11999225
TI  - How did we let it happen?

PMID- 11999227
TI  - Painful plantar heel: an engima.

PMID- 11999226
TI  - Lower respiratory tract infections in HIV infected patients requiring admission
      to hospital.

PMID- 11999228
TI  - And now Auckland.

PMID- 11999229
TI  - Socio-economic factors and death rates.

PMID- 11999230
TI  - Socio-economic factors and mortality among 25-64 year olds followed from 1991 to
      1994: the New Zealand Census-Mortality Study.
AB  - AIM: To measure the association of income, education, occupational class, small
      area socio-economic deprivation, car access and labour force status with
      mortality among 25-64 year old males and females using the 1991 census-cohort of
      the New Zealand Census-Mortality Study. METHODS: Mortality records for 1991-94
      were anonymously and probabilistically linked to 1991 census records, thereby
      creating a cohort study of all New Zealand census respondents. Odds ratios of
      mortality comparing categories of each socio-economic factor were calculated
      using logistic regression. For income, education and deprivation (NZDep91) a
      modified relative index of inequality (RII(10:90)) was calculated. The RII(10:90)
      estimates the relative risk of mortality for low socio-economic people (10th
      percentile rank) compared to high socio-economic people (90 percentile rank)
      allowing direct comparisons across socio-economic factors. RESULTS: The relative
      risk of all-cause mortality for 25-64 year old males with an equivalised
      household income less than $20,000, compared to greater than $50,000, was 2.16
      (95% confidence interval 1.99 to 2.34). For females, this relative risk was 1.68
      (1.52 to 1.86). Using the RII(10:90) all-cause mortality was 2.22, 1.94 and 1.58
      times greater among low compared to high socio-economic males for income, NZDep91
      and education, respectively. For females, these RII(10:90) estimates were 1.77,
      1.69 and 1.57, respectively. By cause of death, the strongest gradients were
      observed for respiratory diseases, followed by lung cancer, cardiovascular
      disease and unintentional injury. For suicide deaths, unemployed males and
      females had 2.70 (1.84 to 3.95) and 2.86 (1.19 to 6.85) greater rates than the
      employed. CONCLUSIONS: There are strong socio-economic gradients for all-cause
      mortality and most specific causes of mortality among both males and female
      adults in New Zealand, regardless of the choice of socio-economic factor. The
      gradients were strongest for income, followed by small area deprivation and
      education, and strongest for 'preventable' causes of death.

PMID- 11999231
TI  - The comparability of community outcomes for European and non-European survivors
      of stroke in New Zealand.
AB  - AIMS: To measure community outcomes for stroke comparing European and non
      European survivors. METHODS: This was a prospective, hospital-based study of
      consecutive patients admitted to three general hospitals in Wellington with acute
      stroke. Patients were assessed using a range of instruments for prestroke
      function, function while in hospital, and then followed for twelve months post
      hospital discharge. Ethnicity was decided by self-report and Maori, Pacific
      people and Asians were grouped together as "non-Europeans" for analysis. RESULTS:
      181 people with stroke were enrolled of whom 171 (94.5%) were followed up to
      death or twelve months post hospital discharge. 33 (18%) were non-European with
      13 (7%) Maori, 14 (8%) Pacific people and 6 (3%) Asians. Non-European survivors
      at twelve months post hospital discharge were more likely to be dependent
      (corrected OR 21.0, 95% CI 3.1, 141), have significantly lower Functional
      Independence Measure scores, lower London Handicap Scores and lower scores on the
      Short Form 36 domains of physical functioning and vitality and Physical Component
      Summary score. CONCLUSIONS: Community outcomes for survivors of stroke may be
      worse for non-Europeans although this should be confirmed in a larger study.

PMID- 11999232
TI  - Management of infectious diseases.

PMID- 11999233
TI  - A hormonal male contraceptive: from wish to reality.

PMID- 11999234
TI  - Public reporting of comparative information about quality of healthcare.

PMID- 11999235
TI  - Will Australian men use male hormonal contraception? A survey of a postpartum
      population.
AB  - AIM: To survey the attitudes of a population of Australian men to potential use
      of male hormonal contraception (MHC). DESIGN: Survey of male partners of women
      who had recently given birth. Men were approached while visiting their female
      partners on the ward. PARTICIPANTS: 118 out of 148 Australian-born English
      speaking men who were approached. SETTING: Postnatal ward of Monash Medical
      Centre (a public teaching hospital in Melbourne), between October 2000 and April
      2001. MAIN OUTCOME MEASURE: Attitudes towards potential use of MHC, rated on a
      five-point scale. RESULTS: 89/118 men surveyed (75.4%; 95% Cl, 67.7%-83.2%)
      indicated that they would consider trying MHC if it were available. The three
      most popular choices for method of administration of MHC were (in descending
      order) an oral pill, a three-monthly injection, or a two-yearly injection. A
      statistically significant association was found between acceptability of
      vasectomy and acceptability of MHC (70.5% of men who indicated they would try MHC
      [MHC "triers"] found vasectomy acceptable versus 44.5% of MHC "non-triers"; P =
      0.011). Triers reported a higher rate of approval of MHC by their female partners
      than non-triers (79.8% v 13.8%, respectively; P < 0.0001). CONCLUSIONS: MHC
      appears to be acceptable to a majority of Australian men when surveyed in a
      postpartum context. Attitudes of men towards existing male contraception, as well
      as the attitudes of their partners, appear to exert a strong influence on
      acceptability of MHC.

PMID- 11999236
TI  - How many patients with coronary heart disease are not achieving their risk-factor
      targets? Experience in Victoria 1996-1998 versus 1999-2000.
AB  - OBJECTIVES: To determine the proportion of patients with established coronary
      heart disease (CHD) in two Australian studies (VIC-I in 1996-1998, and VIC-II in
      1999-2000) who achieved their risk-factor targets as recommended by the National
      Heart Foundation of Australia, and to compare this proportion with those in
      studies from the United Kingdom (ASPIRE), Europe (EUROASPIRE I and II) and the
      United States (L-TAP). DESIGN AND SETTING: Prospective cohort study with VIC-I
      set in a single Melbourne university teaching hospital and VIC-II set in six
      university teaching hospitals in Melbourne, Victoria. PARTICIPANTS: 460 patients
      (112 in VIC-I, 348 in VIC-II) who completed follow-up in the control groups of
      two randomised controlled trials of a coaching intervention in patients with
      established CHD. MAIN OUTCOME MEASURES: The treatment gap (100%, minus the
      percentage of patients achieving the target level for a particular modifiable
      risk factor) at six months after hospitalisation. RESULTS: The treatment gap
      declined from 96.4% (95% CI, 91%-99%) to 74.1% (95% CI, 69%-79%) for total
      cholesterol concentration (TC) < 4.0 mmol/L (P = 0.0001) and from 90.2% (95% CI,
      83%-95%) to 54.0% (95% CI, 49%-59%) for TC < 4.5 mmol/L (P = 0.0001). This
      reduction in the treatment gap between VIC-I and VIC-II appears to be entirely
      explained by an increase in the number of patients prescribed lipid-lowering
      drugs. The treatment gaps in the UK and two European studies were substantially
      greater. The treatment gap for blood pressure (systolic > or = 140 mmHg and/or
      diastolic > or = 90 mmHg) in VIC-II was 39.5%, again less than corresponding
      European data. There were 8.1% of patients who had unrecognised diabetes in VIC
      II (fasting glucose level > or = 7 mmol/L), making a total of 25.6% of VIC-II
      patients with diabetes, self-reported or unrecognised. The proportion of patients
      in VIC-II who were obese (body mass index > or = 30 kg/m2) was similar to the
      overseas studies, while fewer patients in VIC-II smoked compared with those in
      the UK and European studies. CONCLUSIONS: A substantial treatment gap exists in
      Victorian patients with established CHD. The treatment gap compares well with
      international surveys and, at least in the lipid area, is diminishing.

PMID- 11999237
TI  - Postoperative serious adverse events in a teaching hospital: a prospective study.
AB  - OBJECTIVE: To assess the incidence and nature of postoperative serious adverse
      events (SAEs) among inpatients having surgery in a tertiary hospital, and to
      determine which subgroups of patients might be at greatest risk. DESIGN:
      Prospective observational study from 1 December 1998 - 31 March 1999. SETTING:
      Tertiary teaching hospital in Melbourne, Victoria. SUBJECTS: 1,125 subjects
      having inpatient surgery during the study period. MAIN OUTCOME MEASURES:
      Inhospital mortality, length of hospital stay, and SAEs (myocardial infarction,
      pulmonary embolism, acute pulmonary oedema, unscheduled tracheostomy, respiratory
      failure, cardiac arrest, stroke, severe sepsis, acute renal failure, and
      emergency admission to intensive care unit [ICU]). RESULTS: There were 414 SAEs
      in 190 of the 1,125 patients (16.9%); 80 patients died (7.1%). The most common
      adverse events were emergency admission to ICU (95), respiratory failure (52) and
      readmission to ICU (37). In patients without SAEs, mean duration of hospital stay
      was 18.4 days (95% Cl, 15.4-21.4), while in those with SAEs it was 38.5 days (95%
      CI, 35.3-41.7) (P < 0.0001). SAEs, including deaths, were more common after
      unscheduled surgery and in patients over 75 years of age. The combination of
      these two factors carried a 20% mortality. There were no differences in the
      incidence of SAEs among the major surgical specialties. CONCLUSIONS: SAEs are
      common and result in high mortality, especially in older surgical inpatients and
      those having unscheduled surgery. These findings raise important issues of
      optimal perioperative management in tertiary hospitals.

PMID- 11999238
TI  - Hyponatraemia and hypokalaemia due to indapamide.
AB  - OBJECTIVES: To review Australian adverse drug reaction reports describing
      hyponatraemia and hypokalaemia attributed to indapamide and compare the
      characteristics of the patients with those in Australian reports implicating two
      other diuretic products (hydrochlorothiazide and amiloride hydrochloride;
      chlorothiazide). DESIGN: Descriptive analysis using reports from the database of
      the Adverse Drug Reactions Advisory Committee (ADRAC). MAIN OUTCOME MEASURES:
      Numbers of reports of hyponatraemia and hypokalaemia; proportion of such reports
      in total reports of adverse reactions to each drug; severity of electrolyte
      disturbances. RESULTS: Between August 1984 and September 2000, 84 Australian
      reports of hyponatraemia and 87 reports of hypokalaemia, in which indapamide was
      the sole suspected drug, were submitted to ADRAC. Most reports involved an
      indapamide dose of 2.5 mg daily. There was a significantly greater proportion of
      reports of hyponatraemia with indapamide and with the hydrochlorothiazide and
      amiloride combination than with chlorothiazide; hypokalaemia was significantly
      more common for indapamide than for the other two drugs. Of the 87 reports of
      hypokalaemia with indapamide, 35 patients also had hyponatraemia. For all three
      drugs, at least 80% of reports of hyponatraemia were in people aged 65 or over,
      and electrolyte disturbance was most commonly reported in elderly women.
      CONCLUSIONS: Hyponatraemia and hypokalaemia have been described in 20.9% and
      21.7%, respectively, of reports to ADRAC in which indapamide was the sole
      suspected drug. The electrolyte disturbances can be severe.

PMID- 11999239
TI  - Medical harm and the consequences of error for doctors.
AB  - Mistakes in medicine, particularly when patients have suffered harm as a result,
      are of ethical concern as breaching a fundamental injunction in medicine: "first
      do not harm". To minimise the chances of a recurrence, an effective response to
      harm must take into account both the concerns of patients who have been harmed
      and the concerns of doctors who may fear extreme outcomes if a mistake is
      admitted. There is an apparent conflict between a need to respond to errors non
      punitively, on the one hand, and ethical and legal requirements for
      accountability and compensation for anyone harmed, on the other. There is also
      confusion between arguments for a "blame-free" culture in the healthcare system
      and the need to attribute responsibility in some cases. Important elements in an
      ethical response to mistakes include disclosure to the patient and family; taking
      appropriate clinical steps to mitigate any harm that may result from a mistake;
      identifying the process leading to harm; and responding in an appropriate and
      humane manner to minimise the likelihood of any recurrence.

PMID- 11999240
TI  - Ethics, medicine and economics: integration in a hospital environment.

PMID- 11999241
TI  - 1: Infections in pregnant women.
AB  - Some infections are more serious in pregnant than non-pregnant women because of
      the potential for vertical transmission to the fetus or infant (eg, varicella,
      rubella, cytomegalovirus infection, toxoplasmosis and listeriosis). Pre-pregnancy
      or routine antenatal screening for presence of, or susceptibility to, some of
      these infections and appropriate management can prevent adverse fetal or
      perinatal outcomes; screening should include rubella IgG, hepatitis B surface
      antigen, serological tests for syphilis and HIV antibody. If certain other
      vertically transmissible infections are suspected because of a positive antenatal
      test result, confirmatory tests for maternal and, if indicated, fetal infection
      are essential before intervention is considered (eg, cytomegalovirus infection).
      For some vertically transmissible infections that are not readily preventable,
      appropriate management of maternal infection can reduce fetal damage (eg,
      toxoplasmosis).

PMID- 11999242
TI  - Risk of taking oral contraceptives in patients with a history of migraine with
      neurological signs.

PMID- 11999243
TI  - Occupational infection with herpes simplex virus type 1 after a needlestick
      injury.

PMID- 11999244
TI  - Serotonin toxicity with therapeutic doses of dexamphetamine and venlafaxine.

PMID- 11999245
TI  - Venlafaxine and bilateral acute angle closure glaucoma.

PMID- 11999246
TI  - Mirtazapine-induced akathisia.

PMID- 11999247
TI  - Vitamin D deficiency and multicultural Australia.

PMID- 11999248
TI  - Confronting conflict of interest in research organisations: time for national
      action.

PMID- 11999249
TI  - Recent appearance of clindamycin resistance in community-acquired methicillin
      resistant Staphylococcus aureus (MRSA) in south-east Queensland.

PMID- 11999250
TI  - Time for a grant category for curiosity-based research.

PMID- 11999251
TI  - Is it worth screening women over 70 for breast cancer--or indeed any women?

PMID- 11999252
TI  - Hard lessons from a randomised controlled trial.

PMID- 11999253
TI  - Pregnancy loss: a major life event affecting emotional health and well-being.

PMID- 11999254
TI  - Bioterrorism in Australia.

PMID- 11999255
TI  - Guiding antenatal care.

PMID- 11999256
TI  - Are recommendations about routine antenatal care in Australia consistent and
      evidence-based?
AB  - OBJECTIVE: To describe the variability and evidence base of recommendations in
      Australian protocols and national policies about six aspects of routine antenatal
      care. DESIGN: Comparison of recommendations from local protocols, national
      guidelines and research about number of visits, screening for gestational
      diabetes (GDM), syphilis, hepatitis C (HCV), and HIV, and advice on smoking
      cessation. SETTING: Australian public hospitals with more than 200 births/year,
      some smaller hospitals in each State and Territory, and all Divisions of General
      Practice were contacted in 1999 and 2000. We reviewed 107 protocols, which
      included 80% of those requested from hospitals and 92% of those requested from
      Divisions. MAIN OUTCOME MEASURES: Frequency and consistency of recommendations.
      RESULTS: Recommendations about syphilis testing were notable in demonstrating
      consistency between local protocols, national policies and research evidence.
      Most protocols recommended screening for GDM, despite lack of good evidence of
      its effectiveness in improving outcomes. Specific approaches to screening for GDM
      varied widely. Coverage and specific recommendations about testing for HIV and
      HCV were also highly variable. Smoking-cessation information and advice was
      rarely included, despite good evidence of the effectiveness of interventions in
      improving outcomes. No national policies about the number of routine visits and
      smoking cessation could be identified. There were inconsistent national policies
      for both HIV and GDM screening. CONCLUSIONS: Antenatal care recommended in
      protocols used in Australia varies, and is not always consistent with national
      policies or research evidence. Producing and disseminating systematic reviews of
      research evidence and national guidelines might reduce this variability and
      improve the quality of Australian antenatal care.

PMID- 11999257
TI  - Flipped out of control: single-vehicle rollover accidents in the Northern
      Territory.
AB  - OBJECTIVES: To study the incidence of and factors associated with single-vehicle
      rollover (SVRO) accidents in the "Top End" of the Northern Territory (NT); to
      identify factors associated with major injury and death from SVRO accidents.
      DESIGN: Retrospective analysis of records from the NT Department of Transport and
      Works' police database, Royal Darwin Hospital's trauma database, coroner's
      records, and case notes from public hospitals in the Top End. STUDY POPULATION:
      All patients involved in SVRO accidents in the Top End between 1 January 1996 and
      31 December 1997 whose accident was documented by the police, who attended a
      public hospital, or who died. MAIN OUTCOME MEASURES: Types and incidence of all
      accidents; details of the accident scene, vehicle features, and population groups
      associated with SVRO accidents; factors associated with major injury and death.
      RESULTS: SVROs accounted for 30% of all accidents and 29% of all injuries and
      deaths (441 people) in the whole of the NT over the study period. Some of the
      factors associated significantly more frequently with SVRO accidents were (i)
      occurrence of the accident on a straight, dry, unsealed road; (ii) presence of a
      vehicle defect; (iii) travelling at excessive speed; and (iv) the person being
      male, aged 41-50 years, of Aboriginal descent. Among the 147 people who were
      admitted to hospital or died from SVRO accidents in the Top End, major injury
      occurred significantly more frequently if the person was under the influence of
      alcohol, was not wearing a seatbelt and was ejected; if the accident occurred in
      a rural area; and if the vehicle was speeding. Major injuries occurred in 21%
      (31/147), and death was more likely in those with head, chest and neck injuries.
      CONCLUSION: SVRO accidents are a major cause of morbidity and mortality in the
      Top End of the NT. Effective methods of limiting speeding, drink-driving and
      driver fatigue should be sought. Populations most at risk should be targeted.

PMID- 11999258
TI  - Massive tick (Ixodes holocyclus) infestation with delayed facial-nerve palsy.

PMID- 11999259
TI  - Benefits, harms and costs of screening mammography in women 70 years and over: a
      systematic review.
AB  - OBJECTIVE: To assess the (i) benefits, (ii) harms and (iii) costs of continuing
      mammographic screening for women 70 years and over. DATA SOURCES AND SYNTHESIS:
      (i) We conducted a MEDLINE search (1966 - July 2000) for decision-analytic models
      estimating life-expectancy gains from screening in older women. The five studies
      meeting the inclusion criteria were critically appraised using standard criteria.
      We estimated relative benefit from each model's estimate of effectiveness of
      screening in older women relative to that in women aged 50-69 years using the
      same model. (ii) With data from BreastScreen Queensland, we constructed balance
      sheets of the consequences of screening for women in 10-year age groups (40-49 to
      80-89 years), and (iii) we used a validated model to estimate the marginal cost
      effectiveness of extending screening to women 70 years and over. RESULTS: For
      women aged 70-79 years, the relative benefit was estimated as 40%-72%, and 18%
      62% with adjustment for the impact of screening on quality of life. For women
      over 80 years the relative benefit was about a third, and with quality-of-life
      adjustment only 14%, that in women aged 50-69 years. (ii) Of 10,000 Australian
      women participating in ongoing screening, about 400 are recalled for further
      testing, and, depending on age, about 70-112 undergo biopsy and about 19-80
      cancers are detected. (iii) Cost-effectiveness estimates for extending the upper
      age limit for mammographic screening from 69 to 79 years range from $8119 to $27
      751 per quality-adjusted life-year saved, which compares favourably with
      extending screening to women aged 40-49 years (estimated at between $24,000 and
      $65,000 per life-year saved). CONCLUSIONS: Women 70 years and over, in
      consultation with their healthcare providers, may want to decide for themselves
      whether to continue mammographic screening. Decision-support materials are needed
      for women in this age group.

PMID- 11999260
TI  - The demise of a planned randomised controlled trial in an urban Aboriginal
      medical service.
AB  - To fill a gap in knowledge about the effectiveness of brief intervention for
      hazardous alcohol use among Indigenous Australians, we attempted to implement a
      randomised controlled trial in an urban Aboriginal Medical Service (AMS) as a
      joint AMS-university partnership. Because of low numbers of potential
      participants being screened, the RCT was abandoned in favour of a two-part
      "demonstration project". Only 16 clients were recruited for follow-up in six
      months, and the trial was terminated. Clinic, patient, Aboriginal health worker,
      and GP factors, interacting with study design factors, all contributed to our
      inability to implement the trial as designed. The key points to emerge from the
      study are that alcohol misuse is a difficult issue to manage in an Indigenous
      primary health care setting; RCTs involving inevitably complex study protocols
      may not be acceptable or sufficiently adaptable to make them viable in busy,
      Indigenous primary health care settings; and "gold-standard" RCT-derived evidence
      for the effectiveness of many public health interventions in Indigenous primary
      health care settings may never be available, and decisions about appropriate
      interventions will often have to be based on qualitative assessment of
      appropriateness and evidence from other populations and other settings.

PMID- 11999261
TI  - Hindsight bias in medicolegal expert reports.
AB  - Malpractice litigation is now a substantial cost in the provision of healthcare.
      Despite new attitudes of Australian courts towards medical evidence, expert
      reports remain the cornerstone of most medical negligence cases. There is
      evidence that hindsight bias, which may cause the expert to simplify, trivialise
      and criticise retrospectively the decisions of the treating doctor, is inevitable
      when the expert knows there has been an adverse outcome. If possible, outcome
      information should be withheld from experts providing reports. If outcome
      information is not withheld, courts should be made aware of the probability of
      hindsight bias.

PMID- 11999262
TI  - Community versus individual benefit.
AB  - Australian law embodies a "communitarian" conception of the doctor's
      responsibility to respect the confidentiality of the doctor-patient relationship.
      This implies that respect for confidentiality sits alongside two other
      responsibilities: proper care for the patient's general wellbeing and proper
      attention to the safety of the community. Most jurisdictions now require drivers
      to advise their local driver-licensing authority of any permanent or long-term
      injury or illness that affects their ability to drive safely. Some jurisdictions
      require doctors to inform the driver-licensing authority about patients whose
      medical condition may impair their driving to the extent that they are likely to
      endanger the public. If you can not persuade a patient to inform the driver
      licensing authority of the need for an assessment of his or her ability to drive
      safely, then you should inform the relevant authorities yourself.

PMID- 11999263
TI  - Specifying interventions in a clinical trial.

PMID- 11999264
TI  - Does lowering blood pressure prevent recurrent stroke?

PMID- 11999265
TI  - Safety of hormone replacement therapy after mastectomy.

PMID- 11999266
TI  - 2: Hospital-acquired infections.

PMID- 11999267
TI  - Hydrofluoric acid burns from a household rust remover.

PMID- 11999268
TI  - Renal protection by angiotensin II receptor antagonists in patients with type 2
      diabetes.

PMID- 11999269
TI  - Pharmacological treatment of cognitive deficits in Alzheimer's disease.

PMID- 11999270
TI  - Megadose vitamin C in treatment of the common cold: a randomised controlled
      trial.

PMID- 11999271
TI  - High prevalence of coeliac disease in a population-based study from Western
      Australia: a case for screening?

PMID- 11999272
TI  - Evolving evidence and continuing uncertainties for eating disorders.

PMID- 11999273
TI  - FMD: the government publishes its evidence to the lessons learned inquiry as the
      BVA submits its own evidence.

PMID- 11999274
TI  - RCVS criticises organisation and planning. Royal College of Veterinary Surgeons.

PMID- 11999275
TI  - Identification and distribution of a novel Malassezia species yeast on normal
      equine skin.
AB  - This study aimed to investigate the distribution of Malassezia species yeasts on
      the skin of healthy horses. Acetate tape samples were obtained from the lip,
      axilla, interbulbar region, groin and anus of 12 healthy horses. The samples were
      stained and examined microscopically and sites harbouring yeast-like organisms
      were identified. Contact plates were applied to the skin at these sites and
      cultured at 26 degrees C and 32 degrees C. No growth was obtained on horse blood,
      Sabouraud's dextrose or modified Dixon's agar. A pure growth of a Malassezia-type
      organism was obtained on Sabouraud's dextrose agar enriched with oleic acid when
      it was incubated at 30 degrees C. It was identified by 26S ribosomal DNA D1/D2
      sequence analysis as a member of the genus Malassezia, and most closely related
      to Malassezia sympodialis. However, the level of sequence divergence indicated
      that it was a novel species.

PMID- 11999276
TI  - Estimated nutrient content of diets commonly fed to pet birds.
AB  - The owners of 135 pet birds were surveyed by questionnaire to determine their
      birds' weekly food consumption. The birds were divided into six food groups on
      the basis of the amounts of seeds, formulated products and human food they
      consumed. The formulated products and seeds were analysed for their nutrient
      content by two independent laboratories, the nutrient content of the human foods
      was obtained from a standard nutrition reference, and each bird's nutrient intake
      was estimated. The dietary content of individual nutrients was then compared with
      the estimated maintenance requirements for pet birds. Birds consuming less than
      approximately 50 per cent of their diets as formulated products had inadequate
      intakes of vitamins A and D3, and calcium. Diets high in human food were low in
      protein, energy, vitamins and minerals. Diets high in seed were excessive in fat
      and deficient in vitamins A and D3, and calcium.

PMID- 11999277
TI  - Helminth control used by trainers of thoroughbreds in England.
AB  - A telephone survey was conducted of the methods used to control parasitic worms
      at 106 thoroughbred training yards. Most of the horses were allowed access to
      grass and were therefore at risk of infection. The control methods relied
      primarily on the use of anthelmintics and appeared reasonably successful because
      only 44 per cent of trainers reported observing clinical signs of nematode
      infections. They dosed their horses frequently, 40 per cent treating every four
      to six weeks and 25 per cent treating every seven to eight weeks. New arrivals on
      yards were usually treated with anthelmintic but the strategies used would be
      unlikely to prevent the introduction of anthelmintic-resistant nematodes on most
      yards or to deal with encysted cyathostomes. Trainers were responsible for the
      design of most control schemes, and only 42 per cent of them based their choice
      of anthelmintic on veterinary advice.

PMID- 11999278
TI  - Decision analysis tree for deciding whether to remove an undescended testis from
      a young dog.
AB  - A decision analysis tree was constructed to estimate the life span which might be
      expected for a dog presented with cryptorchidism at one year of age if it
      underwent a preventive orchidectomy or if it did not. The tree was constructed by
      using risk factors associated with cryptorchidism and data on the prevalence of
      complications after surgery from the literature. The expected life span without
      an orchidectomy was not significantly different from the expected life span after
      an orchidectomy.

PMID- 11999279
TI  - Influence of Staphylococcus aureus strain on mammary quarter milk production.

PMID- 11999280
TI  - First report of the northern fowl mite Ornithonyssus sylviarum in France.

PMID- 11999281
TI  - Seroprevalence of feline heartworm disease in Tuscany.

PMID- 11999282
TI  - Facilities and quality of training in EU veterinary schools.

PMID- 11999283
TI  - Vets and the future of farming.

PMID- 11999284
TI  - Future of the RCVS library.

PMID- 11999286
TI  - Copycat or designer original?

PMID- 11999285
TI  - Future of the RCVS library.

PMID- 11999287
TI  - Control of leptospirosis by vaccination.

PMID- 11999288
TI  - Need for vigilance in the aftermath of FMD and CSF.

PMID- 11999290
TI  - General pharmacokinetic model for drugs exhibiting target-mediated drug
      disposition.
AB  - Drugs that bind with high affinity and to a significant extent (relative to dose)
      to a pharmacologic target such as an enzyme, receptor, or transporter may exhibit
      nonlinear pharmacokinetic (PK) behavior. Processes such as receptor-mediated
      endocytosis may result in drug elimination. A general PK model for characterizing
      such behavior is described and explored through computer simulations and
      applications to several therapeutic agents. Simulations show that model predicted
      plasma concentration vs. time profiles are expected to be polyexponential with
      steeper distribution phases for lower doses and similar terminal disposition
      phases. Noncompartmental parameters always show apparent Vss and CL(D) decreasing
      with dose, but apparent clearance decreases only when the binding process
      produces drug elimination. The proposed model well captured the time-course of
      drug concentrations for the aldose reductase inhibitor imirestat, the endothelin
      receptor antagonist bosentan, and recombinant human interferon-beta 1a. This type
      of model has a mechanistic basis and considerable utility for fully describing
      the kinetics for various doses of relevant drugs.

PMID- 11999291
TI  - Quantitative relationship between myocardial concentration of tacrolimus and QT
      prolongation in guinea pigs: pharmacokinetic/pharmacodynamic model incorporating
      a site of adverse effect.
AB  - Clinical cases have been reported of tacrolimus (FK506)-induced QT prolongation.
      We have previously demonstrated sustained QT prolongation by FK506 in guinea
      pigs. Herein, we aimed to conduct a pharmacokinetic/pharmacodynamic (PK/PD)
      analysis of FK506, using a model involving the myocardial compartment. The
      pharmacokinetics of FK506 and its effects on QTc intervals were investigated in
      guinea pigs. In the pharmacokinetic study, whole blood and ventricular FK506
      concentrations were analyzed, using a 4-compartment model during and after
      intravenous infusion of FK506 (0.01 or 0.1 mg/hr/kg). Subsequently, the
      concentration-response relationship between ventricular FK506 concentration and
      change in QTc interval was analyzed, using the maximal effect (Emax) model.
      Pharmacokinetic profiles of FK506 showed a delayed distribution of FK506 into the
      ventricle. Furthermore, the observed QT prolongation paralleled the ventricular
      FK506 concentrations, with no lag-time between the two. The Emax model
      successfully described the relationship between changes in QTc interval and
      ventricular FK506 concentrations. In conclusion, the PK/PD model where the
      myocardial drug concentration of FK506 was linked with its adverse effect could
      describe, for the first time, the anti-clockwise hysteresis observed in the
      relationship between blood FK506 concentration and QTprolongation. Such a
      hysteresis pattern for QTprolongation might be caused, therefore, mainly by the
      delayed disposition of FK506 to ventricular myocytes.

PMID- 11999292
TI  - Population pharmacokinetics and pharmacodynamics of sotalol in pediatric patients
      with supraventricular or ventricular tachyarrhythmia.
AB  - AIMS: To derive useful pharmacokinetic (PK) and pharmacodynamic (PD) information
      for guiding the clinical use of sotalol in pediatric patients with
      supraventricular (SVT) or ventricular tachyarrhythmia (VT). METHODS: Two studies
      were conducted in-patients with SVT or VT in the age range between birth and 12
      years old. Both studies used an extemporaneously compounded formulation prepared
      from sotalol HCl tablets. In the PK study, following a single dose of 30 mg/m2
      sotalol, extensive blood samples (n = 10) were taken. The PK-PD study used a dose
      escalation design with doses of 10, 30, and 70 mg/m2, each administered three
      times at 8-hr intervals without a washout. Six ECG recordings for determination
      of QT and RR were obtained prior to the initial dose of sotalol. Four blood
      samples were collected six ECG's were determined during the third interval at
      each dose level. Plasma concentrations of sotalol (C) were assayed by LC/MS/MS.
      The data analysis used NONMEM to obtain the population PK and PD parameter
      estimates. The individual PK and PD parameters were estimated with empirical
      Bayes methodology. RESULTS: A total of 611 C from 58 patients, 477 QTc and 499 RR
      measurements from 23 and 22 patients, respectively, were available for analysis.
      The PK of sotalol was best described by a linear two-compartment model. Oral
      clearance (CL/F) and volume of central compartment (Vc/F) were linearly
      correlated with body surface area (BSA), body weight or age. CL/F was also
      linearly correlated with creatinine clearance. The best predictor for both CL/F
      and Vc/F was BSA. The remaining intersubject coefficients of variation (CV's) in
      CL/F, and Vc/F were 21.6% and 20.3%, respectively. The relationship of QTc to C
      was adequately described by a linear model. The intersubject CV's in slope (SL)
      and intercept (E0) were 56.2 and 4.7%, respectively. The relationship of RR to C
      was also adequately described by a linear model in which the baseline RR and SL
      were related to age or BSA. The intersubject CV's for SL and E0 were 86.7 and
      14.4%, respectively. CONCLUSIONS: BSA is the best predictor for the PK of
      sotalol. Both QTc and RR effects are linearly related to C. No covariates are
      found for the QTc-C relation, while the RR-C relation shows age or BSA
      dependency.

PMID- 11999293
TI  - Information tools for exploratory data analysis in population pharmacokinetics.
AB  - For a group of individuals, population pharmacokinetic studies describe the
      interindividual variability through a statistical distribution. These studies
      conducted during the drug development serve as a useful marker of the safety of
      the drug, provide information that might be decisive for future experiments and,
      in a clinical context, help establish guidelines for optimal use in each patient.
      As complementary tools to the existing statistical and graphical techniques for
      population pharmacokinetic data analysis, indexes derived from information theory
      were used to select the most appropriate modelfor the statistical distribution,
      to detect atypical individuals, and to screen influential covariates. The
      rationale for using these indexes is shown using simulated and real data.

PMID- 11999294
TI  - Genetics, biotechnology and population management of over-abundant mammalian
      wildlife in Australasia.
AB  - Wildlife management involves regulation of population numbers of wild vertebrate
      species. In some cases there are too many animals and in others there are too
      few. Genetic issues arise in both instances. The historical and genetic evidence
      for the number of mammals that were in the founder populations of successful
      colonizing species in Australia and New Zealand is reviewed here. Small numbers
      have often given rise to large populations, despite the concomitant loss of
      genetic variability. Restriction of the number of over-abundant and pest species
      by either physical or chemical methods frequently constitutes very strong
      artificial selection, which leads to rapid genetic change; an example of major
      importance in the two countries is sodium monofluoroacetate (compound 1080).
      Pathogenic agents, surgical sterilization, hormonal contraceptives and
      translocation have all been used with varying degrees of success. The strengths
      and weaknesses of these techniques are assessed. A method that has received much
      attention is immunocontraception. We argue that this attempt to use the animals'
      own immune system to modulate reproduction is incompatible with the basic
      biological function of protection against infectious disease. Immune function
      genes are highly variable in vertebrates, and so often genetic change in the
      population subjected to immunocontraception is likely to be even more rapid than
      is the case with lethal agents. Selection for failure to respond to the
      immunocontraceptive will occur, and will change immune function in general. Poor
      scientific description of ecosystem complexity makes it difficult to predict the
      consequences of immunocontraception on wildlife populations.

PMID- 11999295
TI  - Conservation strategies for Africa's large mammals.
AB  - Africa's large mammals are conserved for their aesthetic, scientific and economic
      values. Many of these species face a gloomy future precipitated by a combination
      of factors directly and indirectly influenced by the activities of man, including
      habitat loss, overexploitation, poor management of designated protected areas,
      and the vulnerability of small isolated populations. Africa's designated
      protected areas and biodiversity hotspots are also under threat, highlighting the
      importance of embracing community participation to address accelerating poverty
      and malnutrition. Innovative strategies are required for the conservation of
      Africa's mammals, such as the integration of a wide range of species in the
      production landscape, including the farming community. Transfrontier conservation
      areas (TFCAs) have been established with the combined objectives of conserving
      biodiversity, creating new jobs in the tourism and wildlife industry, and
      promoting a culture of peace. These areas extend far beyond traditional national
      parks, providing opportunities for integrating large mammals into sustainable
      land-use practices, at the same time as addressing some of the continent's more
      pressing socioeconomic needs. Research on African mammals will inevitably have to
      change direction to accommodate the growing threats and changed circumstances.
      Priorities will include the identification of corridors associated with TFCA
      establishment, the determination of the economic value of certain species in
      consumptive use programmes, research on contraception as a management option in
      restricted areas, and further work on the indirect use value of species. There
      will also be worthwhile opportunities to be pursued with ex situ conservation
      programmes, but these need to be focussed more efficiently.

PMID- 11999296
TI  - Saving the gorillas (Gorilla g. gorilla) and chimpanzees (Pan t. troglodytes) of
      the Congo Basin.
AB  - The forests of the Congo Basin in equatorial Africa are home to significant
      populations of gorillas and chimpanzees. However, numbers are declining owing to
      hunting and to alteration of their habitat. Gorillas and chimpanzees are
      particularly vulnerable for biological reasons: slow reproduction, prolonged
      developmental periods and complex social behaviour. In addition, their capacity
      to recover from disturbance is limited and the reinforcement of wild populations
      with captive-born individuals is rarely an option. Compared with the critically
      endangered mountain gorillas and the beleaguered chimpanzees in forest fragments
      in West Africa, there are some reasons for optimism about the future of the Congo
      Basin apes: levels of threat remain relatively low; and conservation of tropical
      rainforests has become a priority of the international community. At the same
      time, knowledge of the ecological needs of wild apes has increased and non
      invasive techniques now exist to monitor population health. Sadly, no animals
      remain truly 'wild', as their survival depends to a greater or lesser extent on
      management. Protected areas and laws that forbid hunting of vulnerable species
      are classic tools of management, but broader landscape visions are now emerging
      that may allow the Congo Basin to avoid the fragile scenario of larger animals
      persisting only in 'island' parks.

PMID- 11999297
TI  - Australasian marsupials--to cherish and to hold.
AB  - Considerable interchange of mammals between South America and Australasia
      occurred during the first half of the Tertiary, including the presence of
      placental mammals in Australia. This challenges the old assumption that the
      marsupial radiation in Australia was made possible by the absence of placental
      competition, and suggests that two properties of marsupial organization may have
      favoured their survival in the increasingly arid climates that developed after
      the separation of Australasia from Antarctica. The basal metabolic rates of
      marsupials are about 70% of equivalent placentals, so their maintenance
      requirements for energy, nitrogen and water are lower, whereas their field
      metabolic rates are about the same, which means that they have a greater
      metabolic scope to call on when active. This may have given marsupials an
      advantage in semi-arid environments. The lengthy and complex lactation of
      marsupials enables the female to exploit limited resources over an extended
      period without compromising the survival of the young. Both these properties of
      marsupials enabled them to survive the double constraints of low fertility soils
      and the uncertain climate of Australia throughout the Tertiary. The arrival of
      people was followed first by the extinction of the large marsupials and, much
      later, by the wholesale decline or extinction of the small-to-medium sized
      species. The common factor in both extinctions may have been the constraints of
      marsupial reproduction.

PMID- 11999298
TI  - Uncertain breeding: a short history of reproduction in monotremes.
AB  - Although much is known about the biology of monotremes, many important aspects of
      their reproduction remain unclear. Studies over the last century have provided
      valuable information on various aspects of monotreme reproduction including the
      structure and function of their reproductive system, breeding behaviour, sex
      determination and seasonality. All three living genera of monotremes have been
      successfully maintained in captivity, often for long periods, yet breeding has
      been rare and unpredictable. When breeding has occurred, however, significant
      gains in knowledge have ensued; for example a more accurate estimate of the
      gestation period of the platypus and the incubation period for the Tachyglossus
      egg. One of the great challenges for zoos has been to understand why breeding of
      monotremes is difficult to achieve. Analysis of breeding successes of platypuses
      and short-beaked echidnas provides some insights. The evidence suggests that
      although annual breeding seasons are regionally predictable, individual adult
      females breed unpredictably, with some showing breeding intervals of many years.
      The reason for this variation in individual breeding intervals may be resource
      dependant, influenced by social factors or may even be genetically induced.
      Better knowledge of factors that influence breeding intervals may improve the
      success of monotreme captive breeding programmes. More certainty in captive
      breeding is also an important issue for enterprises wishing to trade in
      Australian wildlife since current legislation limits export of Australian fauna
      for display to at least second-generation captive-bred individuals. Given their
      unique evolutionary position, knowledge of reproduction in monotremes needs to be
      gained in advance of any future population declines so that appropriate
      strategies can be developed to ensure their survival.

PMID- 11999299
TI  - Bait-delivered cabergoline for the reproductive control of the red fox (Vulpes
      vulpes): estimating mammalian non-target risk in south-eastern Australia.
AB  - Cabergoline (CAB) is a potent dopamine agonist and an inhibitor of prolactin
      (PRL). In red foxes (Vulpes vulpes), a single oral dose of 100 microg kg(-1) CAB
      can cause abortions and postnatal cub mortality from at least Day 21 of the 52
      day pregnancy. The abortifacient activity of CAB is owing to the suppression of
      PRL, which is essential for luteotrophic support in some eutherian species.
      Postnatal cub mortality probably results from a reduction in the development of
      the mammary ductile system, which is also partially dependant on PRL during
      pregnancy. This paper investigates the potential risks faced by non-target
      mammalian species that may consume CAB baits intended for fox control. Baiting
      with CAB is proposed from 1 August until 1 October each year, to correspond with
      the time that most vixens are pregnant in south-eastern Australia. Thirty-four
      endemic mammals in south-eastern Australia (9 eutherians and 25 marsupials) are
      considered to be potentially bait-consuming (PBC) species. The percentage overlap
      of pregnancy and birth periods for each PBC species was compared with the
      duration of the proposed CAB baiting period. Only Antechinus (3 species) and
      Sminthopsis leucopus have greater than 40% overlap, whereas overlap in endemic
      rodents ranges from 0% to 22%. Overall, most PBC rodent populations appear to
      face little risk from CAB baiting, as their period of pregnancy does not overlap
      significantly with the proposed CAB baiting period. The Antechinus species,
      Phascogale tapoatafa and Dasyurus maculatus, are the only PBC mammals that are
      seasonally mono-oestrous and are thus probably more susceptible to disruption of
      breeding compared with polyoestrous species that may breed many times a year. At
      a baiting density of 8 baits km(-2), theoretical bait availability for small
      dasyurids, rodents and peramelids is low. This suggests a low potential for
      affecting these populations if CAB was indiscriminate in affecting reproductive
      success in all mammal groups. Presently, studies in a limited range of marsupials
      suggest that, unlike eutherians, the marsupial corpus luteum is independent of
      pituitary control and thus suppression of PRL is not likely to cause abortions in
      marsupials. As yet, CAB has not been shown to be orally active in any PBC species
      other than rodents and carnivores. Oral doses of CAB given post partum have not
      been found to affect lactation in Sminthopsis crassicaudata, Trichosurus
      vulpecula, Macropus eugenii and Setonix brachyurus. Further studies are required
      in order to assess the potential for high doses of oral CAB to affect pre-partum
      mammary development and early lactation post partum, especially in peramelids and
      larger dasyurids. Highly target-specific baiting techniques, may eliminate most
      PBC species from being exposed to CAB and these are briefly discussed.

PMID- 11999300
TI  - Farmed deer: new domestic animals defined by controlled breeding.
AB  - The domestication of plants and animals is recognized as pivotal in mankind's
      social evolution. Yet, surprisingly few species have actually been farmed,
      prompting speculation as to which attributes are needed for successful
      domestication. Although red deer were the staple source of meat throughout Europe
      in the mesolithic, they have not been widely domesticated, leading many
      ethologists to argue that they are behaviourally unsuitable. Recently, the most
      widely accepted criterion of domestication, the ability of farmers to control the
      breeding of a species, has been fulfilled in red and other species of deer with
      the widespread adoption of even the most technologically advanced methods of
      artificial breeding. Simultaneously and conversely, the population growth of wild
      deer in many temperate parts of the world has stimulated a search for
      contraceptive techniques.

PMID- 11999301
TI  - Embryo implantation and embryonic stem cell development in primates.
AB  - The endocrine dialogue that results in implantation and the successful
      establishment of pregnancy in primates relies on embryonic secretion of chorionic
      gonadotrophin (CG). This hormone is a signal of embryo viability and capacity to
      support the corpus luteum. The expression of CG is apparently restricted to
      primates. Active or passive immunization of marmoset monkeys against the beta
      subunit of CG prevented implantation and early pregnancy, without disrupting the
      ovarian cycle. Studies of individual embryos cultured in vitro showed that CG is
      secreted at low levels by the blastocyst from before attachment, with secretion
      increasing exponentially after attachment. Gonadotrophin releasing hormone (GnRH)
      was also secreted, from mid-blastocyst stages, before the detection of CG. The
      secretion of GnRH by the embryo continued through the attachment and outgrowth
      stages of embryonic differentiation in vitro. The hypothetical role of GnRH in
      regulating CG release during implantation was tested in recently completed
      experiments. Individual embryos cultured with GnRH, or with agonist or antagonist
      to GnRH, showed significant variations in their secretion of CG and in their
      survival in culture, suggesting a causal relationship between these hormones.
      Embryos cultured with natural GnRH showed enhanced growth and development.
      Embryonic stem cells, from the inner cell mass of marmoset and rhesus monkeys,
      were the first primate embryonic stem cells to be isolated and characterized,
      enabling the subsequent isolation of human embryonic stem cells.

PMID- 11999302
TI  - The derivation and potential use of human embryonic stem cells.
AB  - Human embryonic stem cells lines can be derived from human blastocysts at high
      efficiency (>50%) by immunosurgical isolation of the inner cell mass and culture
      on embryonic fibroblast cell lines. These cells will spontaneously differentiate
      into all the primary embryonic lineages in vitro and in vivo, but they are unable
      to form an integrated embryo or body plan by themselves or when combined with
      trophectoderm cells. They may be directed into a number of specific cell types
      and this enrichment process requires specific growth factors, cell-surface
      molecules, matrix molecules and secreted products of other cell types. Embryonic
      stem (ES) cells are immortal and represent a major potential for cell therapies
      for regenerative medicine. Their use in transplantation may depend on the
      formation of a large bank of suitable human leucocyte antigen (HLA) types or the
      genetic erasure of their HLA expression. Successful transplantation may also
      require induction of tolerance in recipients and ongoing immune suppression.
      Although it is possible to customize ES cells by therapeutic cloning or
      cytoplasmic transfer, it would appear unlikely that these strategies will be used
      extensively for producing ES cells compatible for transplantation. Embryonic stem
      cell research may deliver a new pathway for regenerative medicine.

PMID- 11999303
TI  - Mitochondrial DNA and the Y chromosome: parallels and paradoxes.
AB  - Both mitochondrial DNA (mtDNA) and the Y chromosome have been used extensively by
      molecular paleoanthropologists in attempts to reconstruct human lineages. Both
      are inherited in a haploid manner: mtDNA through the female and the Y through the
      male. For mtDNA, maternal inheritance is ensured by a species-specific mechanism
      of proteolysis of the sperm midpiece in early embryogenesis, based on
      ubiquitination of the mitochondria during spermiogenesis. Both genomes are
      thought to lack recombination and are thus liable to high rates of neutral
      mutation. For the human Y chromosome, it is now clear that there has been
      selection on genes controlling spermatogenesis, resulting in differential long
      term reproductive success. This is corroborated from studies of genealogies and
      hunting-gathering societies, although these lack the rigour provided by the
      modern molecular markers of inheritance. Selection is made more complicated by a
      concentration of genes controlling secondary sexual characteristics on the X
      chromosome. Likewise, mtDNA affects the bioenergetics of gametogenesis and embryo
      development, as well as longevity, disease and the aging process. Both Y
      chromosome and mitochondrial haplotypes show significant associations with
      patterns of male infertility that could distort their use for phylogenetic
      reconstruction. Moreover, the molecular analysis of mtDNA is complicated by the
      presence of numerous nuclear mitochondrial pseudogenes (Numts) that can be
      erroneously amplified by molecular techniques such as PCR. This review examines
      some of these complex interactions and suggests that some of the more contentious
      issues in understanding human evolution may be resolved by considering the
      biology of these genetic markers.

PMID- 11999304
TI  - The road to ovulation: the role of oestrogens.
AB  - Oestrogens have been known for many years to have a direct influence on
      folliculogenesis. Oestradiol-17beta (E2) and its analogues have both
      proliferative and differentiative effects on somatic cells of follicles.
      Nevertheless, definitive proof of an obligatory role for oestrogen in
      folliculogenesis and elucidation of the mechanisms subserving its different
      actions in follicular cells remains elusive. Several recent developments permit a
      re-examination of the roles and actions of E2 in the follicle. They are: (i) the
      discovery of a second form of the oestrogen receptor, ERbeta; (ii) the advent of
      genetically modified mice with deletions in the ERalpha (alphaERKO) ERbeta
      (BERKO) and the double ER deletions (alphabetaERKO); and (iii) a mouse model of
      oestrogen deficiency (ArKO) by targeted disruption of the cyp 19 gene encoding
      the aromatase enzyme. Recent information derived from these models is reviewed to
      re-assess the roles and actions of oestrogens in follicular dynamics and the
      phenotypic differentiation of ovarian somatic cells in the ovary. The data
      demonstrate that oestrogen is obligatory for normal folliculogenesis and that the
      phenotype of the ovarian somatic cells depends on the steroid milieu. The ArKO
      mouse provides a model to test the roles of the respective ERs in proliferation
      and differentiation using specific agonists and antagonists, and to study
      regulation of the differentiation of ovarian and testicular somatic cells.

PMID- 11999305
TI  - Genetic mutations influencing ovulation rate in sheep.
AB  - Ovulation rate in mammals is determined by a complex exchange of endocrine
      signals between the pituitary gland and the ovary, and by paracrine signals
      within ovarian follicles between the oocyte and its adjacent somatic cells. One
      approach to identifying factors regulating ovulation rate is to find mutations
      that influence the target phenotype and, in this context, sheep are proving to be
      remarkable experimental models. Recently, in three sheep families, namely
      Inverdale, Hanna and Booroola, the inherited mutation was mapped to a specific
      region of the sheep X chromosome (Inverdale, Hanna) or sheep chromosome 6
      (Booroola) and in each, a point mutation was identified in genes from the bone
      morphogenetic protein (BMP) relatives of the transforming growth factor beta
      superfamily or their receptors. In Inverdale (I) and Hanna (H) sheep, separate
      point mutations were identified in the BMP15 gene corresponding to sites in the
      mature peptide coding region of the BMP15 growth factor (also known as growth
      differentiation factor 9B; GDF9B). Expression of the BMP15 gene was located
      exclusively in oocytes from the primary stage of follicular growth. There is a
      complete block of normal follicular development in females carrying two copies of
      the Inverdale mutation (II), two copies of the Hanna mutation (HH), or one copy
      of each mutation (HI). Increased ovulation rates are found in females with only
      one copy of either mutation (I+ or H+). In Booroola sheep, a point mutation was
      identified in the highly conserved intracellular serine threonine kinase
      signalling domain of the BMP-1B receptor. Within the ovary, this gene is
      expressed in oocytes in primordial and pre-antral follicles and in granulosa
      cells from the primary stage of growth as well as in corpora lutea. The effect of
      the Booroola mutation is additive for ovulation rate: animals with one copy of
      the mutation have an ovulation rate of 3 or 4, whereas those with two copies have
      an ovulation rate of between 5 and 14. Physiological studies of the above
      mutations demonstrate that the oocyte plays an active role with respect to its
      adjacent somatic cells during follicular development and support the hypothesis
      that the oocyte has a significant influence on the number of follicles that
      proceed to ovulation.

PMID- 11999306
TI  - Angiogenesis in the primate ovary.
AB  - The ovary is distinctive in undergoing cyclic changes in angiogenesis that play a
      critical role in the normal functioning of the female reproductive system. The
      current paper describes the use of the marmoset monkey as an in vivo model in
      which the cellular and molecular regulation of angiogenesis in the ovary can be
      investigated and the effects of manipulation of angiogenic factors elucidated.
      The studies are based on quantifying changes in blood vessel area and endothelial
      cell proliferation, monitoring changes in expression patterns of putative
      angiogenic regulatory factors and targeting these factors by antagonists in vivo.
      Quantification of endothelial cell proliferation shows that angiogenesis
      commences in the pre-antral follicle, increases with follicular development and
      becomes intense in the early corpus luteum. Vascular endothelial growth factor
      (VEGF), a principal angiogenic factor, is synthesized by the developing follicle
      and corpus luteum. Administration of specific antagonists in vivo for selected
      periods of the ovulatory cycle shows that inhibition of VEGF results in a marked
      decrease in endothelial cell proliferation in the follicle and is accompanied by
      a decline in granulosa cell proliferation. Inhibition during the early or mid
      luteal phase results in a marked suppression in luteal angiogenesis, failure of
      development of the microvascular tree and suppression of luteal function.
      Manipulation of angiogenesis should be a novel approach to either promoting or
      inhibiting the normal processes of folliculogenesis, ovulation and corpus luteum
      function.

PMID- 11999307
TI  - The irritable male syndrome.
AB  - The irritable male syndrome (IMS) is a behavioural state of nervousness,
      irritability, lethargy and depression that occurs in adult male mammals following
      withdrawal of testosterone (T). The negative mood state has been described in men
      following withdrawal of androgens and is a striking feature in male seasonally
      breeding mammals associated with the end of the mating season. The Soay ram
      provides an animal model for IMS. Rams exposed to alternating 16-week periods of
      long and short days inactivate the reproductive axis in response to the switch to
      long days; the rapid decrease in T secretion provokes the symptoms of IMS. The
      animals appear agitated and fearful, and the incidence of physical wounding owing
      to fractious inter-male fighting peaks at this time. Androgen and oestrogen
      receptors expressed in cells in the preoptic area and ventromedial/arcuate nuclei
      appear to relay the effects of T on behaviour and gonadotrophin secretion, and
      melatonin receptors expressed in the premammillary area relay the effects of
      melatonin/photoperiod. Changes in the activity of hypothalamic opioidergic,
      dopaminergic and serotonergic neural networks may dictate the interactive effects
      of T and photoperiod. The working hypothesis is that IMS is a transition state
      associated with low hypothalamic amine levels triggered, in part, by the
      withdrawal of opioid peptides.

PMID- 11999308
TI  - Sex and season are major determinants of voluntary food intake in sheep.
AB  - Seasonal changes in voluntary food intake (VFI) are seen in various species,
      including sheep. This paper reviews recent work in this area, especially in
      relation to alterations in the expression of appetite-regulating peptides in the
      brain of the sheep. Work in the hamster is also reviewed because this is another
      species in which VFI is regulated by photoperiod. In normally grazing sheep,
      appetite is maximal in the late summer/early autumn and minimal in spring. This
      appears to be owing to increased expression of the orexigenic peptide,
      neuropeptide Y. Similar results are obtained in sheep that are subjected to
      controlled photoperiod. The same does not appear to be true for hamsters. Further
      work in sheep has shown that there is a seasonal pattern of responsiveness to
      leptin that is more pronounced in females than in males. In particular, the
      effect of leptin to reduce food intake is maximal in female sheep in the spring;
      reasons for the sex difference are discussed.

PMID- 11999309
TI  - Lactational control of reproduction.
AB  - In most mammalian species lactation suppresses fertility. There is no doubt that
      it is the suckling stimulus that provides the controlling signal, and, in human
      reproduction, this is the only truly physiological signal that suppresses
      fertility in normally nourished, healthy women. In breastfeeding women, the
      return of normal fertility follows a relatively well-defined path progressing
      through: an almost complete inhibition of gonadotrophin-releasing
      hormone/luteinizing hormone (GnRH/LH) pulsatile secretion in the early stages of
      lactation; return of erratic pulsatile secretion with some ovarian follicle
      development associated with increases in inhibin B and oestradiol; a resumption
      of apparently normal follicle growth associated with a normal increase in
      oestradiol, but often an absence of ovulation, or formation of an inadequate
      corpus luteum; and a return to normal ovulatory menstrual cycles. A key element
      in controlling the rate of this progression is the impact of the suckling
      stimulus on the GnRH pulse generator, a common feature of lactation in those
      species for which there is information. The variability in the duration of
      lactational amenorrhoea between women is related to the variation in the strength
      of the suckling stimulus, a unique situation between each mother and baby. Full
      breastfeeding can provide a reliable contraceptive effect in the first 6 to 9
      months, but the precise mechanisms whereby the suckling stimulus affects GnRH
      pulsatile secretion remain unknown. Many studies on the hypothalamic pathways
      that might be involved in the translation of the neural suckling stimulus to
      suppression of hypothalamic GnRH secretion have been undertaken, principally in
      rats. In women, suckling increases the sensitivity of the hypothalamus to the
      negative feedback effect of oestradiol on suppressing the GnRH/LH pulse
      generator, a mechanism that appears to be common across species. In contrast, the
      role of prolactin in the control of GnRH appears to be species-dependent, with
      the importance varying from none to an important role in late or throughout
      lactation. In women, there is little evidence for a role of leptin, opioids or
      dopamine, although this may merely reflect the ethical dilemma of being able to
      give sufficient drug to test the system in the mother since these drugs will pass
      through the breast milk to the baby. Regardless of mechanism, practical
      guidelines for using breastfeeding as a natural contraceptive have been
      developed, which allows mothers to utilize the only natural suppressor of
      fertility in women as an effective means of spacing births.

PMID- 11999310
TI  - The equine hypophysis: a gland for all seasons.
AB  - The intrahypophysial mechanisms involved in the control of gonadotrophin
      secretion remain unclear. In the horse, a divergent pattern of gonadotrophins is
      observed at different stages of the reproductive cycle in response to a single
      secretagogue (gonadotrophin-releasing hormone), and dramatic changes in fertility
      take place throughout the year in response to photoperiod. This species thus
      provides a useful model to investigate the regulation of fertility directly at
      the level of the hypophysis. A series of studies were undertaken to examine the
      cytological arrangements and heterogeneity of gonadotrophin storage in the pars
      distalis (PD) and pars tuberalis (PT) of the hypophysis of male and female
      horses. Specifically, the seasonal and gonadal effects on distribution, density
      and hormonal identity of gonadotrophs, the existence of gonadotroph-lactotroph
      associations and the expression of prolactin receptors (PRL-R) as possible
      morphological bases for the differential control of gonadotrophin secretion were
      investigated. It became apparent that both isolated and clustered gonadotrophs
      are normally distributed around the pars intermedia and surrounding capillaries
      in the PD, and in the caudal ventral region of the PT. In the PD, no effects of
      season or of reproductive state on the density or number of gonadotrophs could be
      detected in either male or female animals. In contrast, a fivefold increase in
      gonadotroph density was observed in the PT during the sexually active stage. In
      males, robust gonadal effects were detected on the gonadotroph population;
      orchidectomy significantly reduced both the number and proportion of
      gonadotrophs, in relation to other hypophysial cell types, in both the PD and PT
      regions. Luteinizing hormone (LH) monohormonal, follicle-stimulating hormone
      (FSH) monohormonal and bihormonal gonadotrophs were identified in the PD and PT
      of male and female horses. Interestingly, in males, the relative proportions of
      gonadotroph subtypes and the LH/FSH monohormonal gonadotroph ratio were not
      affected by either season or the presence of the gonads. In contrast, a larger
      proportion of monohormonal gonadotrophs was clearly observed in sexually active
      females. Specific gonadotroph-lactotroph associations and expression of PRL-R in
      cells other than gonadotrophs were detected in the PD throughout the annual
      reproductive cycle. In addition to a stimulatory gonadal effect on lactotroph
      density, a substantial gonadal-independent effect of season was apparent on this
      variable. The findings have revealed important seasonal and gonadal effects on
      the cytological configuration of the equine hypophysis, which may provide the
      morphological basis for the intrahypophysial control of fertility.

PMID- 11999311
TI  - The evolution of neuroendocrine mechanisms regulating sexual behaviour in female
      primates.
AB  - The common marmoset is a small New World primate that lives in extended family
      groups. Female marmosets show rhythmic changes in proceptivity during their 28
      Day ovarian cycle, but fluctuations in sexual receptivity are relatively subtle.
      Receptivity persists even after ovariectomy and adrenalectomy in the female
      marmoset. In the intact female, increases in proceptivity at mid cycle are due to
      the activational effects of oestradiol. Treatment of the ovariectomized female
      with oestradiol-17beta stimulates proceptivity and this effect is blocked by
      thermal or excitotoxic (neuronal cell body specific) lesions in the anterior or
      medial hypothalamus. Implantation of oestradiol into the anterior hypothalamus
      (via guide cannulae) also activates proceptivity. Luteinizing hormone releasing
      hormone (LHRH) may also form part of the neuroendocrine mechanism controlling
      proceptivity in the intact female, given that exogenous LHRH stimulates
      proceptivity in ovariectomized, oestrogen-primed marmosets. These effects of
      oestradiol (and LHRH) on proceptive displays are much more pronounced than any
      effects involving sexual receptivity. Conversely, treatment of the ovariectomized
      female with progesterone, at doses sufficient to produce luteal phase
      concentrations of circulating hormone, causes a marked suppression of
      proceptivity, but only small decreases in sexual receptivity. These experiments
      on marmosets remain some of the very few studies to define how hormones influence
      the brain and sexual behaviour in female primates. They support the conclusion
      that sexual receptivity is not under rigid neuroendocrine control in female
      anthropoids, and that there is no peri-ovulatory period of oestrus, such as
      occurs in most non-primate mammals.

PMID- 11999312
TI  - Male germ cell transplantation: promise and problems.
AB  - Male germ cell transplantation is a novel technique in which donor male stem germ
      cells are surgically transferred to the seminiferous tubules of a recipient
      testis by direct injection or via the rete testis or efferent duct. All germ
      cells that are destined to become stem spermatogonia are defined as male stem
      germ cells, including primordial germ cells from the gonadal ridges, and
      gonocytes and stem spermatogonia from the testis, all of which are transplantable
      and capable of undergoing normal spermatogenesis. Xenotransplantation of male
      germ cells from one species into the testis of another species, including human
      testicular cells in the mouse, has so far proved to be unsuccessful. However, the
      immunodeficient mouse testis can support rat spermatogenesis and produce
      apparently normal rat spermatozoa. The underlying mechanisms remain elusive. The
      present mini-review will focus on the importance of stem spermatogonial
      transplantation for testicular stem cell biology and discuss the likelihood of
      immune rejection after transplantation, which may limit the success of all male
      germ cell transplantation.

PMID- 11999313
TI  - The placenta in multiple pregnancy: outstanding issues.
AB  - The present paper reviews the placental development in multiple gestations and
      highlights the twin-to-twin transfusion syndrome, its recognition and possible
      therapy, and some of the consequences of fetal death of one twin. It presents
      data on discordance for structural anomalies in monozygotic twins. These aspects
      are discussed with respect to their possible pathogenetic origins.

PMID- 11999314
TI  - Equine placentation.
AB  - A tough, elastic glycoprotein capsule envelops the equine blastocyst between Days
      6 and 23 after ovulation. It maintains the spherical configuration of, and
      provides physical support for, the embryo as it traverses the entire uterine
      lumen during Days 6-17, propelled by myometrial contractions that are stimulated
      by pulsatile release of prostaglandin F2alpha and prostaglandin E2. The capsule
      also accumulates constituents of the exocrine secretions of the endometrial
      glands ('uterine milk') as nutrients for the mobile embryo as it releases its
      antiluteolytic maternal recognition-of-pregnancy signal to the whole of the
      surface of the endometrium. Mobility ceases abruptly on Day 17 with a sudden
      increase in uterine tonicity that 'fixes' the conceptus at the base of one of the
      uterine horns. At Day 35, the trophoblast of the spherical conceptus has
      separated into its invasive and non-invasive components. The former,
      distinguished as the thickened, annulate chorionic girdle, invades the maternal
      endometrium to form the unique endometrial cups. These secrete a chorionic
      gonadotrophin that synergizes with pituitary follicle-stimulating hormone to
      induce secondary luteal development in the maternal ovaries. The cup cells
      express foreign fetal antigens that stimulate strong maternal humoral and cell
      mediated immune responses, which curtail their lifespan. The non-invasive
      trophoblast of the allantochorion establishes a stable microvillous contact with
      the endometrial epithelium around Day 40 and, over the next 100 days, develops a
      complex multibranched interdigitation with the endometrium to form the
      microcotyledonary haemotrophic exchange units that cover the entire surface of
      the diffuse epitheliochorial placenta. Reduction in the effective total area of
      fetomaternal contact at this placental interface, by competition between twin
      conceptuses for the limited area of available endometrium, by attachment of the
      allantochorion to an imperfect endometrium in a mare with endometrosis, or
      following cross-breeding or embryo transfer between a sire and dam of dissimilar
      size, will all induce intrauterine growth retardation of the fetus and runting of
      the foal, which persists into adult life. Over 40 years ago, Professor Roger
      Short and his colleagues determined that the high concentrations of conventional
      and unique ring B unsaturated oestrogens in the blood and urine of mares during
      the second half of pregnancy stem from placental aromatization of large
      quantities of C-19 precursor molecules secreted by the temporarily hypertrophic
      fetal gonads. Placental production of progesterone and 5alpha-reduced
      progestagens, on the other hand, depends on both maternal and fetal adrenal
      sources of pregnenelone.

PMID- 11999315
TI  - Conservation of recognition of antibody and T-cell-defined alloantigens between
      species of equids.
AB  - Serological and cellular assays and molecular techniques were used to define
      features of the major histocompatibility complex (MHC) of the donkey With this
      information in hand, immune recognition of MHC determinants within and between
      donkeys and horses was compared. An antibody-mediated, complement-dependent,
      microcytotoxicity assay using a variety of antisera to donkey histocompatibility
      antigens, including those induced as a result of intraspecies or interspecies
      pregnancy in horse mares and jenny donkeys, delineated five donkey leukocyte
      antigen (DoLA) specificities. Antisera raised across species barriers (horse anti
      donkey and donkey anti-horse) recognized polymorphic antigenic determinants in
      the target species. These determinants were often indistinguishable from
      polymorphic antigens recognized by alloantisera raised within horses or donkeys.
      The data indicate that a strong correlation exists between the serological
      antigenic types identified and the specificity of cytotoxic T lymphocytes raised
      by lymphocyte co-cultures, either within or between species. Moreover, in an
      analysis of a small number of donkey MHC class I cDNA gene sequences, no features
      distinguishing horse or donkey MHC class I molecules were identified. These
      molecular findings explain in large measure why antibody- and T-cell-defined
      alloantigen recognition is conserved among these closely related equids.

PMID- 11999316
TI  - Assisted reproductive techniques for hybridization of camelids.
AB  - The camelid family comprises the Old World camelids (or dromedary and Bactrian
      camels) and the New World camelids (namely the llamas, alpacas, guanacos and
      vicunas). Although the species within each group can hybridize among themselves
      to produce fertile offspring, it is only recently that a hybrid between New and
      Old World camelids has been reported. To create this hybrid, semen was collected
      from male camels by artificial vagina (AV) and inseminated into female guanacos
      (n = 9) and llamas (n = 3) at the appropriate stage of their follicular wave
      cycle. Similarly, guanaco and llama semen was collected, also by AV, and
      inseminated into female camels (n = 42). Although several conceptions occurred,
      only one hybrid (camel sire x guanaco dam) continued to term and was born alive
      after 328 days of gestation, and another is pregnant at the time of writing
      (camel sire x llama dam). Further studies are presently being carried out using
      extraspecific embryo transfer to try and improve the success rate of live
      offspring being born. Female guanacos (n = 4) are treated with hormones to
      stimulate their ovaries to produce several follicles before being inseminated
      with camel semen. Of the 12 camel recipients that have to date received hybrid
      embryos (camel sire x guanaco dam), 10 conceived, but 9 of these subsequently
      aborted between 30 and 365 days and only one recipient was still pregnant at the
      time of writing.

PMID- 11999317
TI  - Fetal control of parturition in marsupials.
AB  - Among marsupials, the control of birth is best understood in the tammar wallaby.
      The young is tiny relative to the mother and is highly altricial. Adult female
      tammar wallabies weigh 5 kg, whereas the neonate weighs about 400 mg. However,
      despite this small size, there is clear evidence that the fetus provides the
      signal that sets the timing of birth through several mechanisms. A fetal signal
      activates a nitric oxide-guanylate cyclase system in the myometrium that may
      maintain myometrial inactivity, and this is down-regulated at term. There is also
      up-regulation of prostaglandin (PG) production in the gravid endometrium during
      the last two days of gestation that parallels increased placental PG synthesis,
      and a pregnancy-specific up-regulation of oxytocin receptors in the gravid
      myometrium that increases the responsiveness of the gravid uterus to mesotocin.
      These changes facilitate parturition, but an acute fetus-derived signal appears
      to trigger parturition. The fetal signal is probably related to glucocorticoid
      production. The fetal adrenal matures and is able to synthesize cortisol by Day
      22 of the 26-day gestation. The fetal adrenals double in size between Day 24 and
      term, and their cortisol content increases over 10-fold. The pituitary of the
      neonate contains presumptive corticotrophs, and the adrenals increase cortisol
      production in response to adrenocorticotrophin. Prostaglandin E2, which is
      produced by the placenta, is also a potent stimulant of fetal adrenal cortisol
      synthesis. Treatment of tammars in late gestation with the cortisol agonist,
      dexamethasone, triggers birth around 23 h later. There is thus a strong case that
      fetal adrenal cortisol plays a key role in the preparation for birth and the
      timing of it. Further studies are in progress to more clearly define the
      mechanisms behind these actions of cortisol.

PMID- 11999318
TI  - Germ cells and pluripotent stem cells in the mouse.
AB  - For many years, attempts to achieve long-term culture of mouse primordial germ
      cells (PGCs) proved unsuccessful, even when feeder layers were used and
      individual growth factors were added to the medium. However, when three growth
      factors were added simultaneously to the medium, some of the cells continued to
      proliferate indefinitely. Similar to embryonic stem cell lines, these embryonic
      germ (EG) cell lines were capable of giving rise to embryoid bodies in vitro, and
      colonizing all cell lineages in chimeras, including the germline. Initially, EG
      cells were made from PGCs before migration, 8.5 days post coitum (dpc), and after
      entry into the genital ridge, 11.5 and 12.5 dpc. New EG cell lines from 9.5 dpc
      (migrating) and 11.5 dpc PGCs, carrying either a LacZ or GFP transgene, are
      described here. The developmental potential of the new EG cell lines in vitro, in
      vivo in chimeras, and in tissue aggregates in organ culture was studied. The EG
      cells were compared with PGCs at the stage from which the EG cells were derived.
      The two cell types show several similarities, but also some differences in gene
      expression and cell behaviour, which require further exploration.

PMID- 11999319
TI  - From brain determination to testis determination: evolution of the mammalian sex
      determining gene.
AB  - In mammals, sex is determined by an XY male:XX female sex chromosome system in
      which a male-dominant gene on the Y chromosome (SRY) determines testis formation.
      Sex chromosomes evolved from an ordinary autosome pair as the Y chromosome was
      progressively degraded. The Y chromosome has lost nearly all of its 1500 original
      genes, and those that survived did so because they evolved a critical role in
      male determination or differentiation. SRY is typical of Y-borne genes.
      Comparative gene mapping and sequencing shows that SRY arose quite recently as a
      degraded version of the SOX3 gene on the X chromosome. SOX3 is expressed
      predominantly in brain, and so is more likely to be a brain-determining than a
      testis-determining gene. The male-dominant action of SRYmay be an illusion, as
      its structure suggests that it works by interfering with the action of a related
      gene, which in turn inhibits testis development. This hypothesis can give a good
      account of how a brain-determining gene acquired a role in testis determination
      via differential dosage of SOX3. SRYhas no central role in sex determination and
      it can be replaced as a trigger and loft, as have many other Y-borne genes in
      recent evolutionary history. The absence of SRY in two species of the mole vole
      (Ellobius) suggests that its useful life is already running out.

PMID- 11999320
TI  - The role of 5alpha-reduction in steroid hormone physiology.
AB  - A role for 5alpha-reduction in androgen physiology was first established with the
      recognition that dihydrotestosterone, the 5alpha-reduced metabolite of
      testosterone, is formed in many androgen target tissues, binds to the androgen
      receptor with greater affinity than testosterone, and plays an essential role in
      virilization of the urogenital sinus and urogenital tubercle during male
      development. Two 5alpha-reductases perform this reaction, and both isoenzymes
      utilize NADPH as cofactor and have broad specificity for steroids containing a
      delta4,3-keto configuration. 5alpha-Reduction, which is essentially irreversible,
      flattens the steroid molecule because of altered relation of the A and B rings,
      and stabilizes the hormone-receptor complex. Studies involving in vitro reporter
      gene assays and intact mice in which both isoenzymes are disrupted, indicate that
      the fundamental effect of dihydrotestosterone formation is to amplify hormonal
      signals that can be mediated by testosterone at higher concentrations. 5alpha
      Reduction also plays a role in the action of other steroid hormones, including
      the plant growth hormone, brassinolide, the boar pheromones, androstanol and
      androstenol, progesterone (in some species), and, possibly, aldosterone and
      cortisol. The fact that the reaction is important in plants and animals implies a
      fundamental role in steroid hormone action.

PMID- 11999321
TI  - Sex down under: the differentiation of sexual dimorphisms during marsupial
      development.
AB  - Marsupials have many characteristic features that make them ideal models to study
      the control of sexual differentiation and development. They are distinguished
      from eutherian mammals in their mode of reproduction and their greater dependence
      on the teat and mammary gland than on the placenta for development. They give
      birth to a highly altricial young which completes its development while firmly
      attached to a teat, usually within the confines of a pouch. At birth, the
      marsupial neonate has a well-developed digestive, respiratory and circulatory
      system, but retains its fetal excretory system with a fully functional
      mesonephric kidney and undifferentiated gonads and genitalia.

PMID- 11999322
TI  - Comparative studies on limb morphogenesis in mice and bats: a functional genetic
      approach towards a molecular understanding of diversity in organ formation.
AB  - The basis of species-specific morphogenesis has been a topic of fascination and
      speculation for centuries. In 1828, Karl Ernst von Baer noted that at the
      pharyngula stage of development all vertebrate embryos are morphologically very
      similar. Most subsequent hypotheses have proposed that the vertebrate body plan
      develops by a conserved mechanism, and that divergent forms develop by
      differential elaboration on this basic plan. Gene cloning and expression studies
      have largely confirmed that the genetic pathways of embryonic patterning are
      highly conserved. The finding that the proteins encoded by paralogous and
      orthologous genes within and between species can functionally replace each
      another is no longer novel; in most cases this is the expected result. How, then,
      does divergent morphology arise between species? One hypothesis that fits well
      with comparative data is that divergent morphogenesis arises from genetic
      differences in the timing, level and pattern of orthologous gene expression
      during development. This idea is being tested using a functional genetic approach
      comparing limb morphogenesis between the mouse and bat.

PMID- 11999323
TI  - Pachyderms, primates, plants and population.
AB  - In the past, growth in human population has often been associated with species
      loss. Current rates of population growth, both globally (1 million more births
      than deaths every 103 hours) and regionally, pose a threat of additional
      ecological damage. There is a well-documented unmet demand for family planning in
      nearly all high-fertility countries. Improved family planning and safe abortion
      services will improve the health of women and their families, accelerate
      fertility decline, and help preserve the environment. Many ecologically
      vulnerable areas are especially poorly served by family planning services.
      Examples are given here of improving family planning services through private
      health providers near the Kakamega Forest in western Kenya, and of adding family
      planning choices to a reforestation project run by the Jane Goodall Institute
      near the Gombe National Park, Tanzania. Wildlife biologists can play a critical
      role in identifying local professionals and institutions with the potential to
      improve family planning.

PMID- 11999324
TI  - Biotech prospects for the control of introduced mammals in Australia.
AB  - More than twenty exotic vertebrate species are now listed as pests in Australia.
      Collectively, these pests have a huge economic and environmental impact and pose
      a major threat to Australia's ecosystems and unique biodiversity. Management of
      such pests on a continental scale is a major challenge. Recent advances in
      biotechnology suggest alternatives to the lethal diseases normally sought for use
      as biological control agents. One proposal, being investigated in the Pest Animal
      Control Cooperative Research Centre, Canberra, is the use of biotechnology to
      develop a new generation of agents that act through controlling reproduction to
      prevent the build up of pest populations. The core concept is fertility control
      through immunocontraceptive vaccines delivered by viruses that specifically
      infect the target pest population. Proof of this exciting concept has been
      obtained for the mouse and, very recently, the rabbit, and a candidate vaccine
      vector identified for the fox, portending better control of a trio of Australia's
      most pervasive pests. Other advances in biotechnology suggest ways to negate the
      build up of both innate and acquired immune resistance in target pest populations
      that normally act to limit the efficacy and effective life of biocontrol agents
      in the field. Prospects for extending the use of virally vectored vaccines to the
      field management of wildlife diseases are also identified. Targets for such
      vaccines include a growing suite of emerging diseases, hosted by Australia's
      wildlife, which pose a threat to human and livestock health. Numerous technical
      challenges remain to be addressed before any of these new agents are ready for
      use in the field. However, the major risk to their development is now no longer
      viewed as being technical, but the failure to gain public acceptance for their
      use in the field. This already significant risk is exasperated by the present
      heightened level of public concern about all introductions of genetically
      modified organisms.

PMID- 11999325
TI  - The promise and performance of progestogens as contraceptives.
AB  - Progestogens were first suggested as possible contraceptives in the 1920s, but it
      was not until the early 1960s that effective progestogen-only contraceptive
      methods were developed. Since then it has become possible to deliver a range of
      different progestogens at varying doses, by a variety of routes, over greatly
      differing durations of time. Some of these systems have demonstrated
      extraordinarily high contraceptive efficacy with relatively few side-effects
      apart from unpredictable, but almost universal, disturbances of the menstrual
      pattern. It is now recognized that some systems may exhibit substantial non
      contraceptive health benefits, which should become an important part of the
      overall performance profile of each method. The high technology and differing
      attributes associated with some of the systems raise important considerations in
      relation to user's perceptions and programmatic requirements. Overall,
      progestogens are able to offer women a varied range of valuable choices for
      contraception. The differing performance characteristics of these methods now
      provide women with a major portion of their current contraceptive choices.

PMID- 11999326
TI  - Antigestogens: the holy grail of contraception.
AB  - Progesterone is essential for the establishment and maintenance of pregnancy. The
      discovery of antagonists of progesterone offered the possibility of developing
      new methods of fertility regulation. It was very quickly demonstrated that
      antigestogens would induce bleeding in early pregnancy, and mifepristone in
      combination with a prostaglandin is used as a method of abortion in several
      countries. Mifepristone will also inhibit ovulation, prevent implantation and
      induce menstrual bleeding at the time of expected menses. However, the
      development of these contraceptive uses of antigestogens has been inhibited by
      political and ethical controversy surrounding abortion. Surely the time has come
      to dissociate the ongoing debate about the ethics of abortion from the method so
      that the full therapeutic potential of this class of drugs can be exploited
      fully.

PMID- 11999327
TI  - AIDS and sex education for young people in China.
AB  - Although China has had a rich sexual culture for thousands of years, Chinese
      people are usually unwilling to openly discuss issues of sex. Some parents are
      quite ignorant of the change in their children's sexual attitude and behaviour.
      In China today, adolescents are becoming much more sexually liberated. Premarital
      sex and unplanned pregnancies among teenagers are increasing. Sexually
      transmitted diseases (STD) including HIV/AIDS are also spreading rapidly.
      However, young people lack basic information on AIDS/STD and do not know how to
      protect themselves from these diseases or how to avoid unintended pregnancies.
      Several major youth peer education programmes in China are mentioned in this
      paper. Among them, a four-year programme entitled the Australian-Chinese
      AIDS/STD/Safer Sex Peer Education Programme for Youth, is discussed in some
      detail. The programme has so far reached over 40000 university and school
      students. Evaluation results show that the programme is effective in both
      significantly increasing students' knowledge about AIDS/STDs and changing their
      attitude towards AIDS patients. In addition, the programme is highly praised by
      the students.

PMID- 11999328
TI  - Meeting the contraceptive and AIDS prevention needs of people living on a dollar
      a day.
AB  - The new millennium sees the largest cohort of young people in history entering
      its fertile years. Many of these people are too poor to pay the full cost of
      modern contraception, but the money available for subsidizing their needs is
      exceedingly limited. The AIDS pandemic is placing additional, unprecedented
      demand on already overstretched resources. Existing methods of contraception that
      are well established and off-patent can be produced in bulk at low cost, and will
      remain the backbone of future programmes. The use of misoprostol as an
      abortifacient is likely to spread rapidly. New methods must take into account the
      limitations of the health infrastructure in developing countries and the
      imperative of low cost. Given the constraints of money, skills and facilities, it
      is essential to set realistic priorities for future contraceptive research and
      development. It is suggested that the greatest needs are for a woman-controlled
      method of preventing HIV transmission and for a non-surgical method of female
      sterilization.

PMID- 11999329
TI  - From elephants to AIDS.

PMID- 11999330
TI  - Professor Roger Valentine Short: a biography.

PMID- 11999331
TI  - Anomia for common names and geographical names with preserved retrieval of names
      of people: a semantic memory disorder.
AB  - This paper describes the case of an anomic patient (FH) who is impaired at naming
      pictures of objects but has no difficulties in recalling the names of familiar
      people. Even though his performance on McKenna's (1997) Category Specific Naming
      Test was at the first percentile, he consistently recalled the names of familiar
      people as successfully as controls. It is argued that the pattern of performance
      displayed by FH represents a much clearer double dissociation with proper name
      anomia than any case previously reported (Cipolotti et al., 1993; Semenza and
      Sgaramella, 1993). FH is unable to provide detailed semantic information about
      many of the objects that he cannot name, even though he can recall semantic
      information about familiar people. Consequently his case appears to represent the
      mirror image of the proper name anomic patient (APA) described by Miceli et al.
      (2000) who was unable to recall detailed semantic information about many of the
      people she was unable to name. Further investigation of FH's anomia revealed
      impairments in retrieving both common nouns and verbs, and difficulties in
      retrieving and comprehending geographical names. It is argued that FH's preserved
      ability to name and recall biographical information about people supports the
      view that knowledge about familiar people may be subserved by its own dedicated
      neural subsystem (Kay and Hanley, 1999; Miceli et al., 2000; Gentileschi et al.,
      2001).

PMID- 11999332
TI  - Do pixel-level analyses describe psychological perceptual similarity? A comment
      on 'category-specific naming and the 'visual' characteristics of line drawn
      stimuli' by Laws and Gale.

PMID- 11999333
TI  - Preserved semantic learning in an amnesic patient.
AB  - A case study is reported of an amnesic patient (KN), who displayed an ability to
      learn a substantial body of new visual and verbal semantic concepts, despite
      having a severe deficit in episodic memory. In two experiments, using an
      errorless learning paradigm, he was able to perform at a level close to that of
      his wife, who served as a control subject. When recall of material was retested
      after a delay of several months, during which time there were no further learning
      sessions, his retention was at least as good as, if not better, than that of his
      wife. This is taken as further evidence for the dissociation of semantic and
      episodic processes in amnesia. It also provides further evidence for the role of
      "errorless learning" in efficient acquisition of new facts in amnesia.

PMID- 11999334
TI  - Reading direction and spatial neglect.
AB  - Many American and European investigators have reported that hemispatial neglect
      is more frequent and more severe after right than left hemisphere lesions. This
      hemispheric asymmetry may be due to biological asymmetries, learned behavior, or
      both. Readers of European languages, unlike readers of Semitic languages, scan
      from left to right. Learned rightward scanning may increase the unilateral
      neglect associated with right hemisphere lesions and reduce the severity of
      neglect associated with left hemisphere lesions. To learn if hemispheric
      asymmetries of neglect are influenced by learned scanning behavior, we used line
      bisection and cancellation tasks to study patients with unilateral stroke who
      read only a Semitic or European language before the age of fifteen. We found that
      independent of reading direction, unilateral neglect was more commonly associated
      with right than left hemisphere lesions. After right hemisphere damage right to
      left readers bisected lines closer to center than left to right readers, but on
      the cancellation test readers of European languages did not perform differently
      than readers of Semitic languages. These findings suggest that whereas learned
      scan direction may influence the severity of neglect when measured by line
      bisection, these learned directional scans cannot fully account for the observed
      hemisphere asymmetries of neglect. They also suggest that the line bisection test
      is more influenced by the direction of scanning than is the cancellation test.

PMID- 11999335
TI  - Environmental sound recognition after unilateral subcortical lesions.
AB  - Nonverbal environmental sound recognition was investigated in 24 subjects with
      unilateral subcortical lesions and 20 age-matched normal controls. All patients
      incurred putaminal hemorrhage at least three months before examination, and had a
      cystic lesion under the insula on CT or MRI at the time of evaluation. A mild
      impairment was found in association with extensive damage to the lateral and
      ventral portions of the putamen and the adjacent white matter in either the right
      or left hemisphere. Degree of impairment and type of error did not differ
      significantly between the sides of lesions. These observations and a review of
      literature suggest that the impairment of environmental sound recognition may
      arise with a unilateral subcortical lesion disrupting the geniculo-auditory
      association cortex projection fibers.

PMID- 11999336
TI  - Category-specific naming and the 'visual' characteristics of line drawn stimuli.
AB  - It has been argued that greater intra-category structural similarity for living
      things may make them more difficult to recognize and name (e.g. Humphreys et al.,
      1988). Nevertheless, the precise meaning and quantification of 'structural
      similarity' remain unclear. We developed three new visual measures derived from
      the Snodgrass and Vanderwart (1980) corpus and examined their relationship with
      picture naming in a speeded presentation paradigm. The three measures were: the
      proportion of black pixels (PB); the degree of pixel overlap within subcategories
      using Euclidean Overlap (EO); and the degree of consistency in inter-pixel
      distribution across each picture (IPC). Within-category EO was greater for
      nonliving than living things, indicating less within-category visual overlap for
      living things. Finally, EO correlated significantly with error rates (PB and IPC
      did not). These findings contradict existing notions that line drawings of living
      things have greater visual similarity than nonliving things.

PMID- 11999337
TI  - Normal mere exposure effect with impaired recognition in Alzheimer's disease.
AB  - We investigated the mere exposure effect and the explicit memory in Alzheimer's
      disease (AD) patients and elderly control subjects, using unfamiliar faces.
      During the exposure phase, the subjects estimated the age of briefly flashed
      faces. The mere exposure effect was examined by presenting pairs of faces (old
      and new) and asking participants to select the face they liked. The participants
      were then presented with a forced-choice explicit recognition task. Controls
      subjects exhibited above-chance preference and recognition scores for old faces.
      The AD patients also showed the mere exposure effect but no explicit recognition.
      These results suggest that the processes involved in the mere exposure effect are
      preserved in AD patients despite their impaired explicit recognition. The results
      are discussed in terms of Seamon et al.'s (1995) proposal that processes involved
      in the mere exposure effect are equivalent to those subserving perceptual
      priming. These processes would depend on extrastriate areas which are relatively
      preserved in AD patients.

PMID- 11999338
TI  - Six proposals for freeing online access to the refereed literature and how the
      Cortex initiative can help.

PMID- 11999339
TI  - Monoclonal autoantibodies from patients with autoimmune diseases: specificity,
      affinity and crossreactivity of MAbs binding to cytoskeletal and nucleolar
      epitopes, cartilage antigens and mycobacterial heat-shock protein 60.
AB  - Serum autoantibodies produce typical immunofluorescence staining patterns on HEp
      2 cells, which are frequently used for diagnostic purposes. These include
      antibodies recognizing cytoskeletal and nuclear epitopes. The detailed analysis
      of human monoclonal antibodies (MAbs) should help to understand which antigens or
      autoantigens were involved in the generation of these immune responses. Here,
      three MAbs are described staining HEp-2 cells in a characteristic pattern. They
      were derived from peripheral blood B cells of two patients with rheumatic
      diseases (rheumatoid arthritis and relapsing polychondritis). Their binding
      reactivities were characterized in detail in several assay systems and their
      affinities measured. Although the antibodies differed in their fine specificity
      and crossreactivity, all three MAbs (2 IgM, 1 IgA) bound to purified cytoskeletal
      antigens (desmin) and, in addition, to cartilage antigens (human collagen type
      II, proteoglycans). The binding to HEp-2 cells could be inhibited specifically
      with soluble antigens as shown by intracellular flow cytometry. The affinities
      for both groups of antigens were relatively high (examples: K(D) (desmin) = 0.1 x
      10(-7) M; K(D) (collagen) = 3.5 x 10(-7) M). Two of the MAbs also bound to heat
      shock protein 60 (HSP60) derived from Mycobacterium tuberculosis. The results
      prove that antibodies and B cells with reactivity to both intracellular
      cytoskeletal and nuclear antigens and exogenous antigens (e. g. HSP60) exist in
      patients with rheumatic diseases. Similar to an animal model such human B cells
      may be induced by the exogenous antigen (HSP60) and crossreact with local auto
      antigens related to the disease (cartilage). In this way they might contribute to
      pathogenic processes. Due to their additional crossreactivity with intracellular
      cytoskeletal and nuclear antigens, these antibodies simultaneously can be
      detected in the HEp-2 immunofluorescence assay.

PMID- 11999340
TI  - The lipid raft microdomain-associated protein reggie-1/flotillin-2 is expressed
      in human B cells and localized at the plasma membrane and centrosome in PBMCs.
AB  - Reggie-1/flotillin-2 is a plasma membrane-associated cytoplasmic protein, which
      defines non-caveolar raft microdomains. Reggie-1/flotillin-2 is enriched in
      detergent insoluble (TX100) membrane fractions (DIG), co-localizes with activated
      GPI-linked proteins and the fyn-kinase in neurons and T cells, and thus
      apparently participates in the assembly of protein complexes essential for signal
      transduction. In T cells activated by crosslinking the GPI-linked protein Thy-1
      or by crosslinking the ganglioside GM1, reggie-1/flotillin-2 co-localizes with
      the T cell receptor. To determine whether reggie-1/flotillin-2 is also expressed
      in B cells, primary B cells from human blood and cell lines representing the
      developmental stages of pro, pre, mature and plasma B cells were analyzed by
      Western blotting, RT-PCR and immunofluorescence. Here, we show that reggie
      1/flotillin-2 is expressed throughout B cell development, as well as in primary B
      cells, purified by cell sorting. On non-activated mature B cell Raji cell line we
      found reggie-1/flotillin-2 are exclusively in the detergent (TX100) insoluble
      membrane fractions that are staining positive for the raft marker GM1.
      Immunofluorescence microscopy showed that reggie-1/flotillin-2 is localized at
      the plasma membrane and marks intracellular spots in PBMCs. Confocal co
      localization studies showed that reggie-1/flotillin-2 is associated with the
      plasma membrane, and the centrosomes (microtubule organizing centers) in these
      PBMCs. Comparison of reggie-1/flotillin-2 cDNA sequences with the genomic
      sequence database allowed us to determine the exon/intron structures in mouse and
      human. The gene organizations are highly conserved suggesting an important
      function of reggie-1/flotillin-2. Since reggie/flotillin proteins co-cluster with
      the T cell receptor and fyn kinases upon T cell stimulation, our findings of
      reggie-1/flotillin-2 in B cells suggest a similar role in B cell function.

PMID- 11999341
TI  - Immunoregulatory activities of lactoferrin in the delayed type hypersensitivity
      in mice are mediated by a receptor with affinity to mannose.
AB  - The mannose receptor (MR) mediates clearance of pathogenic microorganisms and
      potentially harmful glycoproteins by recognition of the carbohydrate structures.
      This manuscript describes the significance of the MR in mediation of the
      lactoferrin (LF) effects in delayed type hypersensitivity (DTH) in mice. Here we
      demonstrate that the inhibitory effect of LF on the effector phase of DTH to
      sheep red blood cells (SRBC) was abolished by intraperitoneal (i.p.) pretreatment
      of mice with 50 mg of methyl-alpha-D-mannopyranoside (MMan). Also, we report that
      the inhibition of the effector DTH response to ovalbumin (OVA) was reversed by
      MMan but not by D-galactose (Gal). MMan was found to reduce the adjuvant activity
      of LF given together with OVA, however, did not interfere with the upstimulatory
      effect of the complete Freund's adjuvant. Comparative studies between bovine and
      human lactoferrins (BLF and HLF), revealed that the adjuvant effect of BLF was
      stronger than that of HLF, nevertheless, both effects were inhibited by MMan.
      Thus, we postulate, that MR is a primary receptor for lactoferrin in mediation of
      its some immunotropic activities.

PMID- 11999342
TI  - Effects of pentoxifylline on inflammatory cytokine expression and acute
      pleuropneumonia in swine.
AB  - Pentoxifylline, a methylxanthine derivative and nonspecific type 4
      phosphodiesterase inhibitor, has been used to improve survival of animals with
      sepsis and to attenuate lung injury in acute lung inflammation. The purpose of
      this study was to examine whether pentoxifylline would inhibit the expression of
      inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), and
      thereby decrease the pathophysiology of acute porcine pleuropneumonia. E. coli
      lipopolysaccharide (LPS) and bacterial extracts of A. pleuropneumoniae--induced
      elevations in TNF mRNA which were fully abrogated by addition of pentoxifylline
      in both alveolar macrophage and neutrophil cultures. A 30% reduction in the level
      of LPS-induced interleukin (IL)-1beta mRNA levels also was achieved in
      macrophages. Pentoxifylline did not affect either IL-1alpha or IL-8 expression in
      vitro. Pentoxifylline therapy in vivo significantly reduced the number of band
      neutrophils in swine but did not reduce the pathology associated with
      pleuropneumonia, including changes in serum zinc, iron, or haptoglobin. Neither
      did it alter TNF, IL-1, IL-6, or IL-8 expression. Measurement of pentoxifylline
      and its metabolites in pig sera suggested that efficacious doses of
      pentoxifylline were probably not achieved in vivo. However, subcutaneous doses of
      pentoxifylline higher than 25 mg/kg produced transient diarrhea, vomiting, and
      tremors. These results suggest that pentoxifylline is an effective
      pharmacological tool for the dissection of cytokine regulation in vitro, but
      inhibitory concentrations may not be achievable for in vivo pharmacological use
      in swine.

PMID- 11999343
TI  - Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic
      islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin.
AB  - In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory
      cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a
      critical role in the development of type 1 diabetes, whereas the Th2-type anti
      inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory.
      There are no comprehensive analyses on cytokine profiles in the mouse model of
      diabetes induced with multiple low doses of streptozotocin (MLD-STZ). Therefore,
      we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on
      IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells
      and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine
      transforming growth factor TGF-beta1. C57BL/6 and BALB/c mice of both genders
      were injected intraperitoneally with 40 mg/kg body wt STZ on five consecutive
      days and islets were isolated on day I and 3 after the fifth STZ-injection.
      Control mice received the solvent of STZ. In islets of C57BL/6 mice of both
      genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but
      significantly reduced IL-4 and IL-10 levels in male mice only. Opposite results
      were obtained in islets of BALB/c mice of both genders. Here, MLD-STZ markedly
      decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the
      levels of IL-4 and IL-10. The functional results were in line with MLD-STZ
      effects on the mRNA expression of the cytokines. Moreover, MLD-STZ effects on the
      TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF
      alpha. The in vitro effects of STZ in islets, in general, were similar to those
      exerted by MLD-STZ. Apparently, reduction and upregulation of Th2-type cytokines
      was more associated with susceptibility and resistance, respectively, to MLD-STZ
      induced diabetes than upregulation of Th1-type cytokine levels.

PMID- 11999344
TI  - Systemic immunosuppression fails to suppress cardiac cytokine induction in
      pressure overload hypertrophy in rats.
AB  - BACKGROUND: Activation of cytokines such as interleukin-6 (IL-6) has been
      implicated in the pathogenesis of left ventricular dysfunction and hypertrophy
      since they have been shown to mediate cell proliferation, negative inotropic
      effects and myocardial hypertrophy. However, the effects of immunosuppressive
      therapy on cytokines in the treatment of heart failure and hypertrophy are
      unclear. AIMS: To test the hypothesis that systemic immunosuppresion may
      influence serum and myocardial IL-6 and, thereby, may affect progression of
      myocardial hypertrophy. We studied the effects of chronic treatment with
      methotrexate (MTx) and with the ACE inhibitor ramipril on IL-6 in rats with
      pressure overload left ventricular hypertrophy (LVH) due to aortic banding.
      METHODS: Animals were treated with either vehicle (n = 6) or methotrexate (MTx 1:
      0.3 mg/kg BW/week; MTx 2: 0.9 mg/kg BW/week; i.p.; n = 6 each group) once a week
      during weeks 4-12 after aortic banding; sham-operated rats served as controls
      (CTRL; n = 8). During the development of LVH, serum IL-6 was determined by rat
      specific ELISA and 12 weeks after aortic banding myocardial IL-6 was measured
      using a tissue superfusion technique or determining of protein concentration.
      RESULTS: Aortic banding significantly lowered blood pressure, increased left
      ventricular weight and resulted in elevated serum IL-6 levels (27.6 +/- 5.1 vs
      19.1 +/- 2.3 pg/ml, p < 0.05) compared to CTRL. MTx treatment normalised the
      initially elevated serum IL-6 levels after 8 weeks of treatment. The significant
      increase in IL-6 concentration in the superfusate of all aortic banding groups
      compared to CTRL (< 30%, p < 0.05) was not altered by prior MTx therapy.
      Accordingly, both doses of MTx failed to prevent LVH progression (1.67 +/- 0.23 g
      vs. 2.32 +/- 0.31 g, p < 0.05). In contrast, chronic inhibition of the RAAS not
      only prevents LVH but also reduces myocardial IL-6 concentration (6898 +/- 355
      vs. 3073 +/- 366 pg/mg protein, p < 0.05). CONCLUSION: Pressure overload LVH in
      rats is characterized by an increase in serum levels of IL-6 as well as
      myocardial IL-6. Chronic immunosuppressive therapy normalized systemic IL-6
      levels, but failed to reduce cardiac IL-6 expression and the progression of LVH,
      while ACE inhibition is sufficient to modify LVH and thereby normalises
      myocardial IL-6 expression.

PMID- 11999345
TI  - Modulation of the Th1/Th2 bias by lipopeptide and saponin adjuvants in orally
      immunized mice.
AB  - We compared the adjuvanticity of the synthetic lipopeptide P3CSK4 of bacterial
      origin and the plant-derived adjuvant saponin using the wheat storage protein
      gliadin as antigen. Gluten sensitive BALB/c mice were orally immunized with
      gliadin in a mixture with either lipopeptide or saponin. The gliadin-specific
      serum IgG response was markedly enhanced by the saponin adjuvant. The lipopeptide
      adjuvant enhanced the IgG2a response, but reduced IgG1 production. In contrast,
      the saponin adjuvant enhanced both IgG2a and IgG1, and the sera showed elevated
      specific IgE concentrations. Enhanced specific IgA levels were detected in sera
      and in faeces especially after immunizations with gliadin in combination with
      P3CSK4 Enhanced specific IgG and IgA levels could also be detected in
      supernatants of cell cultures prepared from mesenteric lymph nodes and Peyer's
      patches of immunized mice. Our data suggest that both adjuvants enhance the
      mucosal as well as the systemic immune response; P3CSK4 predominantly elicits the
      activation of the Th1 subset, whereas saponin activates both the Th1 and Th2
      subser. Our findings are of importance for the improvement of mucosal
      immunizations, and might be a tool for the immunotheraphy of food allergies.

PMID- 11999346
TI  - Functional role of phosphatidylinositol 3-kinase in direct tumor lysis by human
      natural killer cells.
AB  - Cytotoxicity is a key function of natural killer (NK) and T cells; yet the
      molecular mechanism is unclear. We have biological, biochemical and molecular
      evidence to demonstrate that phosphatidyl-inositol (PI) 3-kinase is critical for
      direct NK lysis of tumor cells, via control of intracellular granule movement.
      Tumor cell engagement rapidly activated PI 3-kinase in NK cells within 5 min, as
      demonstrated by p85 subunit tyrosine phosphorylation and its ability to generate
      phosphatidylinositol 3-phosphate, PI(3)P, from PI. Wortmannin and LY294002
      effectively inhibited NK cells to lyse 51Cr-labeled tumor cells at the same doses
      that blocked PI-phosphorylating function in tumor-activated NK cells.
      Immunostaining demonstrated that tumor engagement for only 5 min mobilized
      perforin and granzyme B from NK cells unidirectionally towards the target, and
      prior treatment of NK cells with either PI 3-kinase inhibitor effectively stopped
      this intracellular polarization. Lastly, ectopic expression of dominant-negative
      p85 or p110 mutant markedly suppressed NK lytic capacity. These results taken
      together demonstrate that PI 3-kinase may control NK lytic function via granule
      polarization towards the contacted target cell.

PMID- 11999347
TI  - Binding of polyreactive antibodies to self versus foreign antigens.
AB  - Aside from their ability to bind to multiple antigens, the classic hallmark of
      polyreactive antibodies is their autoreactivity. Because of their ability to bind
      a number of common autoantigens, it has long been speculated that polyreactive
      antibodies are involved in the clearance of self-antigens. However, it has been
      demonstrated more recently that polyreactive antibodies are also capable of
      binding to some foreign and synthetic antigens. Although data regarding the
      relative reactivity of polyreactive antibodies with self versus foreign antigens
      is lacking, it is generally thought that both activities may play an important
      biological role. In this study, the relative reactivity of polyclonal human
      polyreactive IgM with human proteins and tissue extracts versus foreign
      (xenogeneic) proteins and tissue extracts was probed. The binding of affinity
      purified anti-ssDNA IgM from adult human serum and the binding of polyreactive
      IgM in human cord serum and in human adult serum were evaluated. Using
      competitive and direct binding assays, human polyreactive IgM were found to be
      generally more reactive with foreign (xenogeneic) proteins than with self or
      allogeneic proteins. These data shed light on the fundamental nature of
      polyreactive antibodies, and may provide additional insight into their putative
      biological roles.

PMID- 11999348
TI  - Hematopoietic cell transplantation as a form of immunotherapy.
AB  - The association of graft-versus-host disease with diminished relapse rates
      following allogeneic hematopoietic cell transplantation, together with the
      dramatic responses sometimes seen following donor lymphocyte infusions,
      demonstrates the considerable power of the human immune system to eradicate
      hematological malignancies. The development of methods that reliably achieve
      complete engraftment of donor lymphohematopoiesis without subjecting patients to
      very-high-dose toxic chemoradiotherapy represents an important step in
      capitalizing on the allogeneic graft-versus-tumor effect. Nonmyeloablative
      hematopoietic cell transplantation can achieve complete chimerism in essentially
      all patients with HLA-matched siblings and the large majority of patients with
      matched unrelated donors. It can be carried out with relative safety, even in
      patients aged up to 70 years. Enduring complete responses have been seen in
      patients with virtually all varieties of hematological malignancies. Current
      studies are defining the role of this procedure in patient management. The
      greater challenge is to further capitalize on this approach by segregating the
      graft-versus-tumor effect from graft-versus-host disease.

PMID- 11999350
TI  - Regulation of hematopoietic stem cell processing and transplantation.
AB  - The widespread use of tissue including hematopoietic stem cell products is
      justification for the development of standards by professional societies and for
      regulation by governmental agencies. The Food and Drug Administration (FDA)
      developed a tiered, risk-based regulatory model. At the low end of risk to the
      tissue recipient, the regulations being developed by the FDA are comparable to
      standards developed by the Foundation for the Accreditation of Hematopoietic Cell
      Therapy (FAHCT) and recognize a basic level of practice in the collection,
      processing, and distribution of hematopoietic stem cell (HSC) products. This
      basic level of practice, when fully enacted, will be found in part 1,271 of
      chapter 21 of the Code of Federal Regulations (CFR), which includes criteria for
      facility management, quality control, donor selection, and the processing of
      cells. The regulatory approach adopted by the FDA is more comprehensive than
      FAHCT standards, however. It defines higher levels of regulatory oversight that
      combines appropriate sections of part 1271 with current good manufacturing
      practice requirements described in parts 210, 211, and 820 of chapter 21 of the
      CFR for HSC products that are more than minimally manipulated.

PMID- 11999349
TI  - Hematopoietic stem cell gene therapy.
AB  - Gene therapy applications that target hematopoietic stem cells (HSCs) offer great
      potential for the treatment of hematologic disease. Despite this promise,
      clinical success has been limited by poor rates of gene transfer, poor
      engraftment of modified cells, and poor levels of gene expression. We describe
      here the basic approach used for HSC gene therapy, briefly review some of the
      seminal clinical trials in the field, and describe several recent advances
      directed toward overcoming these limitations.

PMID- 11999352
TI  - F-blast is a useful marker for differentiating hypocellular refractory anemia
      from aplastic anemia.
AB  - Making a morphologic distinction between hypocellular refractory anemia (hypo RA)
      and aplastic anemia (AA) is difficult. To investigate the significance of
      hemoglobin F-containing erythroblasts (F-blasts) and p53 expression in making the
      distinction between hypo RA and acquired AA, we immunohistochemically assessed F
      blasts and p53 in bone marrow specimens from 16 patients with hypo RA, 31
      patients with acquired AA, and 15 hematologically normal individuals. F-blast
      production was elevated in 87.5% (14/16) of patients with hypo RA, but in only
      3.2% (1/31) of patients with AA (P < .01). p53 was overexpressed in 75.0% (12/16)
      of hypo RA patients and in 6.4% (2/31) of AA patients (P < .01). The mean
      contents of F-blasts and p53-positive cells in patients with hypo RA were 6.31%
      +/- 3.27% and 7.54% +/- 4.36%, respectively, of all bone marrow cells, which were
      significantly higher than for patients with AA (0.35% +/- 0.46% and 0.58% +/-
      1.29%, P < .01). In conclusion, a high prevalence of elevated F-blast production
      is noted in hypo RA, suggesting that the assessment of F-blasts in bone marrow
      can be used as an additional tool for differentiating hypo RA from acquired AA.

PMID- 11999353
TI  - Specimen collection, storage, and transmission to the laboratory for
      hematological tests.

PMID- 11999351
TI  - Angiogenesis in hematologic malignancies and its clinical implications.
AB  - Angiogenesis is defined as a neoformation of blood vessels of capillary origin.
      Hematopoiesis is closely linked with angiogenesis, for they share a common
      ancestor, the hemangioblast. Although it is well established that growth in solid
      tumors is dependent on angiogenesis, its role in hematologic malignancies has not
      yet been clarified. In this review, the direct evidence, ie, increased
      microvessel density, and the indirect evidence, ie, elevated level of angiogenic
      factors or overexpression of messenger RNA or protein of angiogenic factors, for
      and against the role of angiogenesis in the development and progression of
      hematologic malignancies are presented.

PMID- 11999354
TI  - The soluble Notch ligand, Jagged-1, inhibits proliferation of CD34+ macrophage
      progenitors.
AB  - The Notch/Notch ligand system controls diverse cellular processes. The
      proteolytic cleavage generates transmembrane and soluble forms of Notch ligands.
      We examined the effect of a soluble Notch ligand, human Jagged-1, on human cord
      blood (CB) CD34+ cells, under serum-deprived conditions, using soluble human
      Jagged-1-immunoglobulin G1 chimera protein (hJagged-1). Soluble hJagged-1
      inhibited myeloid colony formation but not erythroid-mix or erythroid colony
      formation, in the presence of stem cell factor (SCF), interleukin-3, granulocyte
      macrophage colony-stimulating factor (GM-CSF), G-CSF, thrombopoietin, and
      erythropoietin. Cytological analysis revealed that the decrease in myeloid
      colonies resulted mainly from the inhibition of macrophage colony formation.
      Furthermore, soluble hJagged-1 led to the inhibition of macrophage colony
      formation supported by M-CSF plus SCF and GM-CSF plus SCF. Delayed-addition
      experiments and the analysis of colony sizes demonstrated that soluble hJagged-l
      inhibited the growth of macrophage progenitors by acting in the early stage of
      macrophage development. The direct action of hJagged-1 was confirmed by the
      enhanced expression of the HES-1 (hairy enhancer of the split-1) gene. These
      results suggest that soluble hJagged-1 may regulate human hematopoiesis in the
      monocyte/macrophage lineage.

PMID- 11999355
TI  - PCR-based analysis of alpha-thalassemia in Southern Taiwan.
AB  - The Southeast Asia type deletion of alpha-thalassemia-1 (--SEA) is the most
      common type of alpha-thalassemia-1 in Taiwan. There are 2 less common types,
      Filipino type (--FIL) and Thai type (--THAI). In the current study, we screened
      754 cases of alpha-thalassemia-1 in Southern Taiwan using a polymerase chain
      reaction (PCR)-based method. Our results show that the prevalence of the (--SEA)
      type is 90.6%, followed by the (--FIL) type (8.6%), the (--THAI) type (0.5%), and
      the (-alpha(3.7/-alpha(3.7)) type (0.3%). We also analyzed the genotypes of 96
      patients with hemoglobin (Hb) H disease and 48 cases of hydrops fetalis with Hb
      Bart's. The frequencies of the genotypes of the alpha-thalassemia-1 allele in Hb
      H disease are in accordance with the results of analyses of alpha-thalassemia-1
      cases. The alpha-thalassemia-2 allele includes alpha(4.2), alpha(G), alpha(CS),
      and alpha(QS)alpha. Forty-one cases, 6 cases, and 1 case of hydrops fetalis with
      Hb Bart's were caused by --SEA/--SEA, --SEA/--FIL and --SEA/--THAI respectively.
      The genotypes and frequencies of alpha-thalassemia in this study are different
      from those in previous studies in Taiwan and Hong Kong. These differences may be
      attributed to the diverse genetic origin among different ethnic groups and the
      extensive inclusion of the (--FIL) and (--THAI) alpha-thalassemia-1 types.

PMID- 11999356
TI  - More than 13 years of hypereosinophila associated with clonal CD3-CD4+
      lymphocytosis of TH2/TH0 type.
AB  - A 65-year-old Japanese woman was referred to our hospital because of
      hypereosinophilia lasting for more than 10 years, and skin ulceration, especially
      on the hands. Closer examination revealed the clonal proliferation of CD3-CD4+T
      lymphocytes. The patient had generalized pruritus without severe end-organ
      involvement and high serum levels of IgE. A diagnosis of monoclonal CD3-CD4+ T
      lymphocyte-associated idiopathic hypereosinophilic syndrome (HES) was made based
      on these findings. This case showed that this newly recognized entity of HES is
      not restricted to Western countries. The abnormal T-cell clone was not merely TH2
      type but was clearly TH2/TH0 type. Although this disease is considered
      prelymphoma, this patient did not develop lymphoma during more than 13 years of
      follow-up. Therefore, in some patients, clonal CD3-CD4+ lymphocyte-associated HES
      may take a more indolent course. In this subgroup, the control of clinical
      manifestations seems very important. In the present case, treatment with
      hydroxyurea quite dramatically improved the intractable skin manifestations,
      although the treatment lessened only the number of peripheral eosinophils and not
      the number of clonal CD3-CD4+ T-lymphocytes.

PMID- 11999357
TI  - Successful immunosuppressive therapy with cyclosporine A for posthepatitis B-cell
      deficiency with activated cytoplasmic interferon--gamma-positive T-lymphocytes.
AB  - We describe a patient with transient disappearance of B-cells,
      hypogammaglobulinemia, and mild pancytopenia after acute hepatitis. Both HLA
      DR+CD8+ and intracellular interferon-gamma+/interleukin-4- cell levels were
      markedly increased, resulting in an increase in the cytotoxic T-cell (T(C))1/Tc2
      and helper T-cell (T(H))1/T(H)2 ratios. After immunosuppressive therapy with
      cyclosporine A, these parameters of T-cell activation were clearly decreased, and
      hematologic recovery, including an increase in B-lymphocytes and immunoglobulin
      concentration, was obtained. These results suggest that there had been
      suppression of B-cells by activated T-cells. Some patients with common variable
      immunodeficiency show similar activation of T-cell function, and the present
      findings suggest the possibility of immunosuppressive therapy for such patients.

PMID- 11999358
TI  - Biological significance of proliferation, apoptosis, cytokines, and
      monocyte/macrophage cells in bone marrow biopsies of 145 patients with
      myelodysplastic syndrome.
AB  - Labeling index (LI), apoptosis, levels of 2 pro-apoptotic cytokines tumor
      necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(TGF-beta),
      and the number of monocyte/macrophage cells that are the likely source of the
      cytokines were simultaneously measured in plastic-embedded bone marrow (BM)
      biopsy sections of 145 patients with myelodysplastic syndromes (MDS). TNF-alpha
      was correlated with TGF-beta (P = .001) and with monocyte/macrophage cells (P =
      .003). Patients with excess blasts in their marrows had a higher TGF-beta level
      (P = .01) and monocyte/macrophage number (P = .05). In a linear regression
      model,TGF-beta emerged as the most significant biological difference between
      patients who have excess of blasts and those who do not (P = .01). We conclude
      that in addition to TNF-alpha, TGF-beta also plays a significant role in the
      initiation and pathogenesis of MDS, and that a more precise definition of its
      role will likely identify better preventive and therapeutic strategies.

PMID- 11999359
TI  - Monitoring minimal residual disease in patients with MLL-AF6 fusion transcript
      positive acute myeloid leukemia following allogeneic bone marrow transplantation.
AB  - Acute myeloid leukemia (AML) patients with chromosome 11q23 abnormalities or MLL
      rearrangements have a poor prognosis when treated with conventional chemotherapy.
      However, the efficacy of allogeneic bone marrow transplantation (BMT) for this
      type of leukemia is not yet clear. We describe 2 MLL-AF6 fusion transcript
      positive AML patients treated with allogeneic BMT who were monitored for minimal
      residual disease (MRD) by reverse transcriptase polymerase chain reaction.
      Although long survival or cure of this type of AML is rarely reported, 1 patient
      had durable remissions. Fusion transcripts disappeared in 1 patient but not in
      the other, even after the graft-versus-host disease effect was increased by the
      discontinuation of immmunosuppressive therapy. This is the first report of MRD
      and the probability of graft-versus-leukemia effects following BMT in AML
      patients who are MLL-AF6 fusion transcript positive.

PMID- 11999360
TI  - Reversible acceleration of disease progression following cyclosporin A treatment
      in a patient with myelodysplastic syndrome.
AB  - A 38-year-old Japanese man with myelodysplastic syndrome (MDS), whose bone marrow
      smears demonstrated hypercellularity, was treated with oral cyclosporin A (CsA)
      therapy. During the course of this therapy, the numbers of peripheral blood and
      bone marrow blasts increased and the level of serum lactate dehydrogenase
      increased. After discontinuation of CsA treatment, all of these levels rapidly
      decreased. We consider that CsA might accelerate disease progression in certain
      MDS cases.

PMID- 11999361
TI  - A pleural effusion caused by fibrous hematopoietic tumor successfully treated
      with prednisolone in a patient with agnogenic myeloid metaplasia with
      myelofibrosis.
AB  - A 46-year-old woman suffering from agnogenic myeloid metaplasia (AMM) since 1994
      was being followed as an outpatient. In November 1999, she exhibited respiratory
      failure caused by massive pulmonary effusion, which was speculated to have been
      produced by chest tumors. A biopsy specimen revealed findings compatible with
      fibrous hematopoietic tumor (FHT): prominent fibroblasts and fibrosis with scantv
      megakaryocytes. Serum concentrations of transforming growth factor (TGF)-beta and
      platelet-derived growth factor (PDGF) were significantly higher than those of
      other cases of AMM without FHT. The effusion did not respond to administrations
      of various chemotherapeutic agents, but after prednisolone administration, the
      effusion disappeared and the tumors also diminished. TGF-beta and PDGF were the
      possible causes of FHT formation, and for such fibrotic extramedullary regions,
      the administration of prednisolone should be considered.

PMID- 11999362
TI  - Acute basophilic leukemia lacking basophil-specific antigens: the importance of
      cytokine receptor expression in differential diagnosis.
AB  - De novo acute basophilic leukemia (ABL) is a rare form of myeloid leukemia. The
      low prevalence of ABL makes it difficult to define its clinical characteristics
      and to establish an effective therapeutic protocol. We present here a case of de
      novo ABL in a 64-year-old Japanese man. The diagnosis of ABL depended on the
      following: (1) metachromasia with toluidine blue stain, (2) intracytoplasmic
      theta granules identified by electron microscopy, and (3) findings obtained from
      extensive immunophenotypic analysis. Although blast cells lacked basophil
      specific antigens such as CDw17, CD88, and FcepsilonRI, an expression profile of
      cytokine receptors including CD116 (GM-CSF receptor), CD117 (c-kit), and CD123
      (IL-3 receptor alpha) helped to define the cellular lineage in our case. The
      patient achieved complete remission with intensive chemotherapy composed of
      idarubicin and cytosine arabinoside and was disease free during the following 30
      months. We propose that immunophenotyping, especially focusing on cytokine
      receptors, is useful in diagnosing ABL.

PMID- 11999363
TI  - T-cell prolymphocytic leukemia with hemorrhagic gastrointestinal involvement and
      a new chromosomal abnormality.
AB  - We report a case of T-cell prolymphocytic leukemia in a 56-year-old woman who
      exhibited hemorrhaging with gastric involvement as the first manifestation. This
      patient's condition was diagnosed as T-cell prolymphocytic leukemia based on the
      findings of lymphocytosis, abnormal immunophenotype, hepatosplenomegaly,
      lymphadenopathy, and cutaneous involvement. Endoscopic examination of the upper
      gastrointestinal tract revealed hemorrhage from a gastric lesion with
      histological involvement. Cytogenetic analysis revealed chromosomal
      abnormalities, 46,XX,der(1), add(1)(p36), that have not previously been described
      in T-cell prolymphocytic leukemia. In spite of a transient response to
      chemotherapy, the patient died 15 months after onset of the disease.

PMID- 11999364
TI  - Second allogeneic hematopoietic stem cell transplantation for leukemia relapse
      after first allogeneic transplantation: outcome of 16 patients in a single
      institution.
AB  - Sixteen patients who underwent a second allogeneic hematopoietic stem cell
      transplantation (HSCT2) for leukemia relapse after the first allogeneic
      transplantation (HSCT1) were studied. The patients included 7 patients with acute
      myelogenous leukemia, 8 with acute lymphoblastic leukemia, and 1 with chronic
      myelogenous leukemia. The median patient age at HSCT2 was 22 years (range, 12 to
      44 years). The median interval between HSCT1 and HSCT2 was 19 months (range, 2 to
      46 months). At HSCT2, 7 patients were in complete remission (CR), 7 had relapsed,
      and 2 had bone marrow aplasia. In 14 patients, donors for HSCT2 were the same as
      those for HSCT1. Two donors were replaced, 1 for another HLA-matched sibling and
      1 for an unrelated cord blood donor. Four patients (25%) died within 100 days
      after HSCT2 from veno-occlusive disease, sepsis, interstitial pneumonitis, or
      chronic graft-versus-host disease (GVHD), without leukemia relapse. Seven
      patients (44%) developed leukemia relapse and died between 4 and 20 months after
      HSCT2. Five patients (31%) survived beyond 4 years. One patient died from chronic
      GVHD without leukemia relapse 55 months after HSCT2. The 4 other patients were
      alive between 79 and 134 months after HSCT2 (median follow-up, 106 months).
      Factors that favorably influenced survival were age younger than 20 years and CR
      duration after HSCT1 longer than 12 months. HSCT2 is considered to be beneficial
      for select patients. Preparative regimens, GVHD prophylaxis, and donor choice for
      HSCT2 need to be studied to obtain a more successful outcome for HSCT2.

PMID- 11999365
TI  - Retrospective study on the impact of hepatitis B and hepatitis C virus infection
      on hematopoietic stem cell transplantation in Japan.
AB  - We performed a retrospective survey in 62 hematopoietic cell transplantation
      (HCT) centers in Japan in which all HCTs performed between 1986 and 1998 were
      reviewed, and those involving hepatitis B virus surface antigen (HBsAg)-positive
      donors were identified. One hundred and thirty-five patients who underwent
      allogeneic HCT (alloHCT) were studied for complications related to hepatitis B
      virus (HBV) or hepatitis C virus (HCV). The median follow-up period was 24
      months. Positivity for HBsAg was observed in 32 patients (24%) throughout the
      study. Twenty-six of the 32 patients were HBsAg carriers before alloHCT, whereas
      the remaining 6 became HBsAg(+) after alloHCT. Forty-two recipients were anti-HBs
      antibody (HBsAb)-positive, and 58 recipients (43%) were HCV Ab(+). Eleven of 26
      (42%) HBsAg(+) recipients survived between >4 and >119 months. Six of 26 cases
      received transplants from HBsAg(+) donors, and, although they had not developed
      acute graft-versus-host disease, 4 of 6 died of hepatic and renal failure within
      10 months after HCT. After transplantation, 5 patients showed serologic evidence
      of HBV reactivation, whereas 4 patients showed evidence of an immune response to
      HBV. Viral reactivation occurred during the tapering of the immunosuppressive
      agent. However, 3 of 5 were alive at the time of this report, suggesting that
      reactivation is not directly correlated with severe liver dysfunction. Seventeen
      patients (13%) of 135 recipients developed hepatic failure. Eight (47%) of 17
      were diagnosed with fulminant hepatitis and 5 (29%) with veno-occlusive disease
      (VOD). VOD was observed in 12% of both HBsAg(+) and HCVAb(+) patients. In this
      study, the relatively high incidence of HBV events occurred after alloHCT, and,
      therefore, we should consider a protocol for active immunization of donors and
      recipients against HBV. Moreover, although the presence of HBV or HCV is not a
      contraindication for alloHCT, we recommend a careful follow-up of recipients
      after transplantation, especially during immunosuppression tapering.

PMID- 11999366
TI  - Ocular manifestation of acute graft-versus-host disease after allogeneic
      peripheral blood stem cell transplantation.
AB  - A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral
      blood stem cell transplantation from an HLA-identical brother. Eighteen days
      after transplantation, the patient developed grade II acute graft-versus-host
      disease (GVHD) and was treated with corticosteroids. On day 38, the patient
      complained of eye pain and lacrimation. A slitlamp examination revealed corneal
      ulcers and pseudomembranous formation in both eyes. Histologic and
      immunohistochemical examinations of the pseudomembrane disclosed an infiltrate
      dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence
      in situ hybridization identified a Y chromosome in the infiltrated mononuclear
      cells. Surveillance cultures from conjunctival swabs were negative. Thus, we
      diagnosed these ocular manifestations as an ocular involvement of acute GVHD.

PMID- 11999367
TI  - A case of hypoplastic chronic myelogenous leukemia initiating with pancytopenia.

PMID- 11999368
TI  - Tsutsugamushi disease (scrub typhus)-associated hemophagocytic syndrome.

PMID- 11999369
TI  - A thaumatin-like gene in nonclimacteric pepper fruits used as molecular marker in
      probing disease resistance, ripening, and sugar accumulation.
AB  - During pepper (Capsicum annuum) fruit ripening, the ripe fruit interaction with
      the anthracnose fungus, Colletotrichum gloeosporioides, is generally
      incompatible. However, the unripe fruit can interact compatibly with the fungus.
      A gene, designated PepTLP (for pepper thaumatin-like protein), was isolated and
      characterized by using mRNA differential display. The PepTLP gene encodes a
      protein homologous to other thaumatin-like proteins and contains 16 conserved
      cysteine residues and the consensus pattern of thaumatin. PepTLP gene expression
      is developmentally regulated during ripening. The accumulation of PepTLP mRNA and
      PepTLP protein in the incompatible interaction was higher than that in the
      compatible one. Furthermore, PepTLP gene expression was stimulated by both
      jasmonic acid treatment and wounding during ripening, but by wounding only in the
      unripe fruit. Immunolocalization studies showed that it is localized to the
      intercellular spaces among cortical cells. The expression of the PepTLP gene upon
      fungal infection was a rise from the early-breaker fruit. The development of
      anthracnose became significantly prevented with beginning of fruit ripening, and
      the sum total of sugar accumulation increased. The results suggest that the
      PepTLP gene can be used as a molecular marker in probing for disease resistance,
      ripening, and sugar accumulation in nonclimacteric pepper fruits.

PMID- 11999370
TI  - Do 14-3-3 proteins and plasma membrane H+-AtPases interact in the barley
      epidermis in response to the barley powdery mildew fungus?
AB  - 14-3-3 proteins form a family of highly conserved proteins with central roles in
      many eukaryotic signalling networks. In plants, they bind to and activate the
      plasma membrane H+-ATPase, creating a binding site for the phytotoxin fusicoccin.
      Barley 14-3-3 transcripts accumulate in the epidermis upon inoculation with the
      powdery mildew fungus. We have isolated a cDNA encoding a plasma membrane H+
      ATPase (HvHAI), which is also induced by powdery mildew attack. The C-terminal
      domain of this H+-ATPase interacts with 14-3-3 proteins in the yeast two-hybrid
      system. Inoculation with the powdery mildew fungus, or treatment with fusicoccin,
      results in an increase in fusicoccin binding ability of barley leaf membranes.
      Overlay assays show a fungus-induced increase in binding of digoxygenin-labelled
      14-3-3 protein to several proteins including a 100 kDa membrane protein, probably
      the plasma membrane H+-ATPase. These effects are seen specifically in the
      inoculated epidermis and not in the whole leaf. We propose that 14-3-3 proteins
      are involved in an epidermis-specific response to the powdery mildew fungus,
      possibly via an activation of the plasma membrane H+-ATPase.

PMID- 11999371
TI  - Small Cab-like proteins regulating tetrapyrrole biosynthesis in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - In the cyanobacterium Synechocystis sp. PCC 6803 five open reading frames (scpA
      scpE) have been identified that code for single-helix proteins resembling helices
      I and III of chlorophyll a/b-binding (Cab) antenna proteins from higher plants.
      They have been named SCPs (small Cab-like proteins). Deletion of a single scp
      gene in a wild-type or in a photosystem I-less (PS I-less) strain has little
      effect. However, the effects of functional deletion of scpB or scpE were
      remarkable under conditions where chlorophyll availability was limited. When
      cells of a strain lacking PS I and chlL (coding for a polypeptide needed for
      light-independent protochlorophyllide reduction) were grown in darkness, the
      phycobilin and protochlorophyllide levels decreased upon deletion of scpB or scpE
      and the protoheme level was reduced in the strain lacking scpE. Addition of delta
      aminolevulinic acid (ALA) in darkness drastically increased the level of Mg
      protoporphyrin IX and Mg-protoporphyrin IX monomethyl ester in the PS I-less/ch/L
      /scpE- strain, whereas PChlide accumulated in the PS I-less/chlL-/scpB- strain.
      In the PS I-less/chlL- control strain ALA supplementation did not lead to large
      changes in the levels of tetrapyrrole biosynthesis intermediates. We propose that
      ScpE and ScpB regulate tetrapyrrole biosynthesis as a function of pigment
      availability. This regulation occurs primarily at an early step of tetrapyrrole
      biosynthesis, prior to ALA. In view of the conserved nature of chlorophyll
      binding sites in these proteins, it seems likely that regulation by SCPs occurs
      as a function of chlorophyll availability, with SCPs activating chlorophyll
      biosynthesis steps when they do not have pigments bound.

PMID- 11999372
TI  - Identification of a tRNA isopentenyltransferase gene from Arabidopsis thaliana.
AB  - The tRNA of most organisms contain modified adenines called cytokinins. Situated
      next to the anticodon, they have been shown to influence translational fidelity
      and efficiency. The enzyme that synthesizes cytokinins on pre-tRNA, tRNA
      isopentenyltransferase (EC 2.5.1.8), has been studied in micro-organisms like
      Escherichia coli and SaccharomYces cerevisiae, and the corresponding genes have
      been cloned. We here report the first cloning and functional characterization of
      a homologous gene from a plant, Arabidopsis thaliana. Expression in S. cerevisiae
      showed that the gene can complement the anti-suppressor phenotype of a mutant
      that lacks MOD5, the intrinsic tRNA isopentenyltransferase gene. This was
      accompanied by the reintroduction of isopentenyladenosine in the tRNA. The
      Arabidopsis gene is constitutively expressed in seedling tissues.

PMID- 11999374
TI  - Pollination modulates expression of the PPAL gene, a pistil-specific beta
      expansin.
AB  - Using differential screening we isolated a pistil-specific cDNA clone
      corresponding to a 1.2 kb mRNA and encoding a 32.5 kDa protein. The amino acid
      sequence shared similarity with that of group-I grass pollen allergens, which are
      known to have expansin activity. This clone, which later showed to share homology
      also with beta-expansins, was named PPAL. The PPAL mRNA was specifically
      expressed in the secretory zone of the stigma and in the epidermal layer of the
      placenta. The accumulation level of the transcript increased during pollination,
      and the protein was secreted in the stigmatic exudate of the tobacco flower. We
      suggest here that PPAL is a new expansin, acting as a cell-wall-loosening agent
      during pollination.

PMID- 11999373
TI  - Characterization of a tissue-specific and developmentally regulated beta-1,3
      glucanase gene in pea (Pisum sativum).
AB  - As part of a search for seed coat-specific expressed genes in Pisum sativum cv.
      Finale by PCR-based methods, we identified and isolated a cDNA encoding a beta-
      1,3-glucanase, designated PsGNS2. The deduced peptide sequence of PsGNS2 is
      similar to a subfamily of beta-1,3-glucanases, which is characterized by the
      presence of a long amino acid extension at the C-terminal end compared to the
      other beta-1,3-glucanases. PsGNS2 is expressed in young flowers and in the seed
      coat and is weakly expressed in vegetative tissues (roots and stems) during
      seedling development. It is not inducible by environmental stress or in response
      to fungal infection. In developing pea flowers the transcript is detectable in
      all four whirls. In the seed coat the expression is temporally and spatially
      regulated. High abundance of the transcript became visible in the seed coat when
      the embryo reached the late heart stage and remained until the mid seed-filling
      stage. In situ hybridization data demonstrated that the expression of PsGNS2 is
      restricted to a strip of the inner parenchyma tissue of the seed coat, which is
      involved in temporary starch accumulation and embryo nutrition. This tissue
      showed also less callose deposits than the other ones. The 5' genomic region of
      PsGNS2 was isolated and promoter activity studies in transgenic Medicago
      truncatula showed a seed-specific expression. Highest activity of the promoter
      was found in the seed coat and in the endosperm part of the seed.

PMID- 11999375
TI  - The western red cedar (Thuja plicata) 8-8' DIRIGENT family displays diverse
      expression patterns and conserved monolignol coupling specificity.
AB  - The isolation and characterization of a multigene family of the first class of
      dirigent proteins (namely that mainly involved in 8-8' coupling leading to (+)
      pinoresinol in this case) is reported, this comprising of nine western red cedar
      (Thuja plicata) DIRIGENT genes (DIR1-9) of 72-99.5% identity to each other. Their
      corresponding cDNA clones had coding regions for 180-183 amino acids with each
      having a predicted molecular mass of ca. 20 kDa including the signal peptide.
      Real time-PCR established that the DIRIGENT isovariants were differentially
      expressed during growth and development of T. plicata (P < 0.05). The
      phylogenetic relationships and the rates and patterns of nucleotide substitution
      suggest that the DIRIGENT gene may have evolved via paralogous expansion at an
      early stage of vascular plant diversification. Thereafter, western red cedar
      paralogues have maintained an high homogeneity presumably via a concerted
      evolutionary mode. This, in turn, is assumed to be the driving force for the
      differential formation of 8-8'-linked pinoresinol derived (poly)lignans in the
      needles, stems, bark and branches, as well as for massive accumulation of 8-8'
      linked plicatic acid-derived (poly)lignans in heartwood.

PMID- 11999376
TI  - Comparative analysis of the plant mRNA-destabilizing element, DST, in mammalian
      and tobacco cells.
AB  - The labile SAUR transcripts from higher plants contain a conserved DST sequence
      in their 3'-untranslated regions. Two copies of a DST sequence from soybean are
      sufficient to destabilize reporter transcripts in cultured tobacco cells whereas
      variants bearing mutations in the conserved ATAGAT or GTA regions are inactive.
      To investigate the potential for conserved recognition components in mammalian
      and plant cells, we examined the function of this instability determinant in
      mouse NIH3T3 fibroblasts and tobacco BY2 cells. In fibroblasts, a tetrameric DST
      element from soybean accelerated deadenylation and decay of a reporter
      transcript. However, a version mutated in the ATAGAT region was equally effective
      in this regard, and a tetrameric DST element from Arabidopsis was inactive. In
      contrast, the soybean DST element was more active as an mRNA instability element
      than the mutant version and the Arabidopsis element, when tested as tetramers in
      tobacco cells. Hence, the plant DST element is not recognized in animal cells
      with the same sequence requirements as in plant cells. Therefore, its mode of
      recognition appears to be plant-specific.

PMID- 11999377
TI  - Spatial and temporal expression of the orchid floral homeotic gene DOMADS1 is
      mediated by its upstream regulatory regions.
AB  - The orchid floral homeotic gene, DOMADSI, is a marker gene specifically expressed
      in the transitional shoot apical meristem during floral transition in Dendrobium
      Madame Thong-In. DOMADSI is not detectable in vegetative tissues except a weak
      expression in the stem. Its transcript is uniformly localized in both of the
      inflorescence meristem and floral primordia, and later expressed in almost all of
      the floral organs. We isolated and sequenced a 3.5 kb DOMADSI promoter fragment
      upstream of the transcription start site, demonstrating the location of several
      putative DNA-binding sites, through which MADS-box and class I knox genes may
      modulate the DOMADSI expression. To gain insight into the molecular basis of the
      regulation of DOMADS1, deletion analysis of the DOMADSI::beta-glucuronidase (GUS)
      gene fusions was performed by means of the stable orchid transformation systems.
      The study shows that the full-length upstream promoter sequence confers the same
      spatial and temporal GUS staining pattern as that of the distribution of DOMADSI
      RNA during orchid development. We also identified the distinct cis-acting
      regulatory regions required for the control of DOMADS1 expression in vegetative
      and reproductive tissues, as well as the shoot apical meristem during floral
      transition.

PMID- 11999378
TI  - A maize r1 gene is regulated post-transcriptionally by differential splicing of
      its leader.
AB  - Anthocyanin biosynthesis in Zea mays is controlled by regulatory genes of the
      r1/b1 family that encode bHLH transcription factors. Analysis of the 381
      nucleotide leader sequence of a member of this family, Sn, discloses the presence
      of five ATG triplets upstream of the coding region and three upstream open
      reading frames (uORFs) of 38, 15 and 13 amino acids respectively. RT-PCR studies
      revealed that a splicing event occurs in the leader region in the different
      tissues tested. Splicing deletes 146 nucleotides which include uORF2 and uORF3.
      By trans-activation experiments in maize protoplasts we find that the spliced
      leader, compared to the non-spliced one, reduces the number of pigmented
      protoplasts by four-fold. We suggest a multilevel regulation of the Sn
      transcription factor acting not only at the transcriptional but also at the post
      transcriptional level.

PMID- 11999379
TI  - The amount of thiolic antioxidant ingestion needed to improve several immune
      functions is higher in aged than in adult mice.
AB  - With aging there is an increase of oxidative stress due to an imbalance between
      the oxidant production and the antioxidant levels in favor of the former. Since
      immune cell functions are specially linked to reactive oxygen species (ROS)
      generation, the oxidant/antioxidant balance is essential for these cells.
      Although low levels of antioxidants cause a decrease in immune function, very
      high levels of antioxidant compounds could show prooxidant effects. In the
      present work, we have studied the effect of diet supplementation, for 4 weeks,
      with two different doses of two thiolic antioxidants, namely thioproline (TP) and
      N-acetylcysteine (NAC), at 0.1% (w/w) and 0.3% (w/w, of each antioxidant) on the
      main immune system cells, i.e.: macrophages, lymphocytes and natural killer (NK)
      cells of adult (33+/-1 week old) and aged (75+/-1 week old) female Swiss mice.
      Two groups of animals, adult and aged mice, fed standard diet were used as
      controls. The results show that the ingestion of 0.1% doses of thiols improves,
      in the adult mice, several immune functions such as the chemotaxis capacity of
      both macrophages and lymphocytes, the phagocytosis of macrophages, the
      lymphoproliferative response to the mitogen Con A and the NK activity. Moreover,
      no change was observed in adherence capacity of immune cells, and superoxide
      production was decreased. By contrast, in aged mice the ingestion of these
      amounts of antioxidants did not change the immune functions studied with the
      exception of NK activity, which was stimulated. The ingestion of 0.3% of
      antioxidants by adult mice only increased some immune functions such as adherence
      and superoxide production, which are markers of oxidative stress. Other functions
      such as chemotaxis or lymphoproliferative response decreased. However, the
      ingestion of these very high amounts of thiols by aged animals increased the
      phagocytosis, the NK activity and specially the lymphoproliferative response to
      the mitogen, a function that is very depressed with aging.

PMID- 11999380
TI  - New insight on the relationship between LDL composition, associated proteins,
      oxidative resistance and preparation procedure.
AB  - Oxidized low density lipoprotein (LDL) plays an important role in atherogenesis.
      It is generally thought that LDL is mainly oxidized in the intima of vessel
      walls, surrounded by hydrophilic antioxidants and proteins such as albumin. The
      aim of this study was to investigate the possible interrelationships between
      oxidation resistance of LDL and its protein and lipid moieties. Proteins and to a
      lesser extent lipids, appeared to be the major determinants in the LDL Cu2+
      oxidation resistance, which in turn depend on the ultracentrifugation (UC)
      procedure used. Comparing high speed/short time (HS/ST, 4 h), high speed/long
      time (HS/LT, 6-16h) and low speed/long time (LS/LT, 24h) conditions of UC, HS
      with the shortest time (4h) led to prepare LDL (named LDL.HS-4 h) with higher
      total protein and triglyceride contents, unchanged total cholesterol,
      phospholipids and Vitamin E, and higher Cu2+-oxidation resistance. Among
      proteins, only albumin allows to explain changes. PAF acetyl hydrolase appeared
      to be unaffected, whereas its pro-oxidant role was established and found only in
      the absence of albumin. In contrast the pro-oxidant role of caeruloplasmin took
      place regardless of the albumin content of LDL. The antioxidant effect of albumin
      (the oxidation lag time was doubled for 20mol/mol albumin per LDL) is assumed to
      be due to its capacity at decreasing LDL affinity for Cu2+. Interestingly, the
      LDL.HS-4 h albumin content mirrored the intrinsic characteristics of LDL in the
      plasma and was not affected by added free albumin. Moreover, it has been verified
      that in 121 healthy subjects albumin was the best resistance predictor of the
      Cu2+-oxidation of LDL.HS-4 h, with a multiple regression equation: lag time (min)
      = 62.1 + 0.67(HSA/apoB) + 0.02(TG/apoB)-0.01(TC/apoB); r = 0.54, P < 0.0001.
      Accounted for by lag time, the oxidation resistance did not correlate with alpha
      tocopherol and ubiquinol contents of LDL. The mean albumin content was about
      10mol/mol, and highly variable (0-58 mol/mol) with subjects. The LDL.HS-4h may
      account for the status of LDL in its natural environment more adequately than LDL
      resulting from other conditions of UC.

PMID- 11999381
TI  - Protective effect of spin trap agent, N-tert-butyl-alpha-phenylnitrone on
      hyperoxia-induced oxidative stress and its potential as a nitric oxide donor.
AB  - We have previously suggested that the spin trap agent, N-tert-butyl-alpha
      phenylnitrone (PBN) can function not only as an antioxidant but also as a nitric
      oxide (NO) donor. To characterize the pharmacological activities of PBN against
      oxidative damage, we examined the effect of PBN on NO generation under hyperoxic
      conditions. The formation of NO in mice exposed to 95% oxygen was determined
      using a NOx analyzer and electron spin resonance (ESR). Levels of NOx, an
      oxidative product of NO, increased in the blood of mice under these conditions.
      However, the increase was returned to a normal level by the NOS (nitric oxide
      synthase) inhibitor, L-NMMA, indicating that the NO was formed via a biosynthetic
      pathway. In addition, ESR spectra of the liver and brain of control and
      experimental mice that were measured using Fe(DETC)2 as an NO trap reagent showed
      strong ESR signals from NO complexes in the livers of mice exposed to 95% oxygen.
      When examining the effect of PBN in mice, PBN reduced the NOx formation in the
      blood under the same hyperoxic conditions. In addition, the ESR intensity of the
      NO complex was weaker in the PBN-treated mice than in the non-treated mice,
      showing that PBN possess anti-inflammatory properties. However, under a normal
      atmosphere, NOx and ESR analyses showed that NO levels increased in PBN-treated
      mice but not in control mice. These findings suggested that PBN functions as an
      NO donor under specific physiological conditions. PBN appears to protect against
      hyperoxia-induced NO toxicity by anti-inflammatory action rather than by serving
      as an NO donor.

PMID- 11999382
TI  - The redox state of glutathione, cysteine and homocysteine in the extracellular
      fluid in the skin.
AB  - Glutathione, the most abundant low-molecular weight thiol in the skin, has been
      shown to protect the skin from both photobiological and chemical injury. The
      thiols, glutathione in particular, have also been shown to be crucially involved
      in defence against contact allergens. Since the levels of extracellular thiol
      concentrations are important determinants of intracellular thiol status, we have
      compared the normal concentrations and the redox status of the main low-molecular
      weight thiol components in the extracellular fluid at the dermo-epidermal
      junction with the corresponding plasma levels. In their sulfhydryl form, all
      three thiols, i.e. glutathione, cysteine and homocysteine, were more abundant in
      experimental skin blister fluid than in plasma, as were the free disulfides of
      glutathione and homocysteine, whereas the free disulfides of cysteine were about
      the same in blister fluid and in plasma. Protein mixed disulfide levels were
      higher in plasma than in blister fluid. The present results provide information
      concerning the extracellular defence in the skin.

PMID- 11999383
TI  - Gender differences in steady-state levels of oxidative damage to DNA in healthy
      individuals.
AB  - Oxidative damage to DNA has often been used as a biomarker for oxidative stress
      and more specifically for cancer risk. Indeed, the measurement of oxidative
      damage to DNA, particularly of 8-hydroxyguanine (8OHG) and 8-hydroxy-2'
      deoxyguanosine (8OHdG), has been adopted as a method for establishing the effects
      of antioxidant supplementation towards protection from certain cancers,
      cardiovascular and neuro-degenerative diseases, both in patients and healthy
      individuals. However, reported levels of 8OHdG or 8OHG vary considerably,
      possibly due to the different methodologies used, and only few data are available
      for the non-smoking and the female population. In this paper, steady-state levels
      of oxidative damage to DNA measured in a group of 20 males and 19 females are
      reported. Significant gender differences in levels of modified DNA bases such as
      2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPy guanine), 8-hydroxyadenine
      (8OHA) and 5-hydroxycytosine (5OHC), measured by gas chromatography-mass
      spectrometry (GC/MS), were observed. The results are discussed in relation to the
      Vitamin C and iron status of the subjects and to the existing, yet limited,
      literature data. The role of gender in predisposition to oxidative damage to DNA
      needs to be addressed in future studies.

PMID- 11999384
TI  - Oxysterols as indices of oxidative stress in man after paraquat ingestion.
AB  - The aim of this study is to evaluate oxidative stress in man after paraquat
      ingestion by analyzing 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha
      and 7beta-OOH) as well as oxysterols, cholesterol oxidation products, as indices
      of lipid peroxidation. Lung, kidney, and liver were collected at autopsy from
      seven patients with paraquat poisoning and seven controls matched for age and
      sex. We identified for the first time 7-ketocholesterol (7-keto) and 7
      hydroxycholesterol (7alpha-OH and 7beta-OH) in human kidney by LC-MS. Next, we
      quantified 7alpha-OOH and 7beta-OOH by HPLC with postcolumn chemiluminescence as
      well as oxysterols by HPLC-UV. Both 7alpha-OOH and 7beta-OOH detected in lung and
      kidney from the controls were as low as the paraquat group. In contrast, we found
      both 7-keto and 7beta-OH in lung and 7-keto in kidney from the paraquat group
      were significantly higher than from the controls. This is the first report on
      accumulated oxysterols in lung and kidney from human paraquat poisoning. It seems
      to reflect greater oxidative stress in the pathology of paraquat intoxication.

PMID- 11999385
TI  - Heat shock preconditioning reduces the formation of 8-hydroxy-2'-deoxyguanosine
      and 4-hydroxy-2-nonenal modified proteins in ischemia-reperfused liver of rats.
AB  - Heat shock preconditioning (HSPC) is a promising strategy for providing ischemic
      tolerance. The objective of this study is to investigate the effectiveness of
      HSPC in preventing oxidative damage of cellular proteins and DNA during ischemia
      reperfusion of the liver. Male Wistar rats were divided into a heat shock group
      (group HS) and control (group C). Forty-eight hours prior to ischemia, rats in
      group HS received HSPC at 42 degrees C for 15 min. All rats received hepatic warm
      ischemia for 30min and subsequent reperfusion. The formation of 8-hydroxy-2'
      deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE) modified proteins in liver
      tissue, survival rate of the animals, and changes in biochemical and histological
      parameters were compared between groups. Heat shock protein 72 was produced only
      in group HS. The 7-day survival of rats was significantly better in group HS
      (10/10) than in group C (5/10) (p < 0.01). The serum release of alanine
      aminotransferase (n = 10, p < 0.01) and the concentration of adenosine
      triphosphate in liver tissue (n = 10, p < 0.01) 40min after reperfusion was
      significantly better in group HS than in group C. The formation of 8-OHdG in
      liver tissue measured by high-performance liquid chromatography was suppressed in
      group HS (p < 0.01). The production of HNE-modified proteins as determined by
      Western-blot analysis was also decreased in group HS. These results were also
      confirmed by immunohistochemical analysis. As determined by levels of 8-OHdG and
      HNE-modified proteins produced during ischemia-reperfusion of the liver, HSPC
      reduced the oxidative injury of cellular proteins and DNA in the liver tissue.

PMID- 11999386
TI  - Assessment of antioxidant activity by using different in vitro methods.
AB  - In this study, six common tests for measuring antioxidant activity were evaluated
      by comparing four antioxidants and applying them to beverages (tea and juices):
      Trolox equivalent antioxidant capacity assay (TEAC I-III assay), Total radical
      trapping antioxidant parameter assay (TRAP assay), 2,2-diphenyl-l-picrylhydrazyl
      assay (DPPH assay), N,N-dimethyl-p-phenylendiamine assay (DMPD assay),
      Photochemiluminescence assay (PCL assay) and Ferric reducing ability of plasma
      assay (FRAP assay). The antioxidants included gallic acid representing the group
      of polyphenols, uric acid as the main antioxidant in human plasma, ascorbic acid
      as a vitamin widely spread in fruits and Trolox as water soluble vitamin E
      analogue. The six methods presented can be divided into two groups depending on
      the oxidising reagent. Five methods use organic radical producers (TEAC I-III,
      TRAP, DPPH, DMPD, PCL) and one method works with metal ions for oxidation (FRAP).
      Another difference between these tests is the reaction procedure. Three assays
      use the delay in oxidation and determine the lag phase as parameter for the
      antioxidant activity (TEAC I, TRAP, PCL). They determine the delay of radical
      generation as well as the ability to scavenge the radical. In contrast, the
      assays TEAC II and III, DPPH, DMPD and FRAP analyse the ability to reduce the
      radical cation (TEAC II and III, DPPH, DMPD) or the ferric ion (FRAP). The three
      tests acting by radical reduction use preformed radicals and determine the
      decrease in absorbance while the FRAP assay measures the formed ferrous ions by
      increased absorbance. Gallic acid was the strongest antioxidant in all tests with
      exception of the DMPD assay. In contrast, uric acid and ascorbic acid showed low
      activity in some assays. Most of the assays determine the antioxidant activity in
      the micromolar range needing minutes to hours. Only one assay (PCL) is able to
      analyse the antioxidant activity in the nanomolar range. Black currant juice
      showed highest antioxidant activity in all tests compared to tea, apple juice and
      tomato juice. Despite these differences, results of these in vitro assays give an
      idea of the protective efficacy of secondary plant products. It is strongly
      recommended to use at least two methods due to the differences between the test
      systems investigated.

PMID- 11999387
TI  - Oxidative stress in very low birth weight infants as measured by urinary 8-OHdG.
AB  - Very low birth weight (VLBW) infants can be subjected to oxidative stress in the
      course of intensive care. We measured 8-hydroxydeoxyguanosine (8-OHdG), a
      biomarker of oxidative stress, and estimated the degree of oxidative stress in
      such infants. We also examined if the administered oxygen was related to
      oxidative stress. Urine samples of 50 Japanese VLBW infants [birth weights:
      956.3+/-277.6g, and gestational ages: 28.0+/-2.6 weeks (mean +/- SD)] were
      collected on various postnatal days and 8-OHdG levels were determined using an
      ELISA kit. Sixteen term infants served as normal controls. As body weights at
      sampling increased, the average levels of urinary 8-OHdG decreased. 8
      Hydroxydeoxyguanosine levels were: infants under 1000g, 29.5+/-16.4 micromol/mol
      creatinine (n = 24); 1000-1500g, 23.8+/-14.9 (n = 12); over 1500g, 16.1+/-8.5 (n
      = 14); and control, 10.9+/-7.2 (n = 16). Significant differences were found
      between <1000g group and > or = 1500g group (p = 0.0030), <1000g group and
      control (p < 0.0001), and 1000-1500g group and control (p = 0.0108). Also as
      postconceptional age at sampling increased, the average levels of 8-OHdG
      decreased. 8-Hydroxydeoxyguanosine levels were: infants before 252 days (36
      weeks) of postconception: 27.4+/-15.5 micromol/mol creatinine (n = 34); after 252
      days, 18.2+/-12.5 (n = 16). Differences between <252 days group and control (p <
      0.0001), and <252 days group and > or = 252 days groups (p = 0.0253) were
      statistically significant. Among the three groups based on ambient oxygen
      concentration (21%, 22-29%, and > or = 30%) there was no significant difference
      (p = 0.417). The more premature the infants were, the more intense was the
      oxidative stress, hence, it is the prematurity rather than the administered
      oxygen which causes oxidative stress in VLBW infants. Drury et al. ["Urinary 8
      hydroxydeoxyguanosine in infants and children" Free Radic. Res. 28 (1998) 423
      4281 measured urinary 8-OHdG of 28 infants (24-40 weeks gestation) and found no
      gestation or birthweight related differences. This discrepancy seemed to be
      because of difference in birth weights and sampling period of the subjects.

PMID- 11999388
TI  - Response of the cultivated tomato and its wild salt-tolerant relative
      Lycopersicon pennellii to salt-dependent oxidative stress: increased activities
      of antioxidant enzymes in root plastids.
AB  - Root plastids of the cultivated tomato Lycopersicon esculentum (Lem) exhibited
      salt-induced oxidative stress as indicated by the increased H2O2 and lipid
      peroxidation levels which were accompanied with increased contents of the
      oxidized forms of ascorbate and glutathione. In contrast, H2O2 level decreased,
      lipid peroxidation level slightly decreased and the levels of the reduced forms
      of ascorbate and glutathione increased in plastids of L. pennellii (Lpa) species
      in response to salinity. This better protection of Lpa root plastids from salt
      induced oxidative stress was correlated with increased activities of superoxide
      dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidases (POD),
      monodehydroascorbate reductase (MDHAR), glutathione peroxidase (GPX), glutathione
      S-transferase (GST) and phospholipid hydroperoxide glutathione peroxidase
      (PHGPX). In the plastids of both species, activities of SOD, APX, and POD could
      be resolved into several isozymes. In Lem plastids two Cu/ZnSOD isozymes were
      found whereas in Lpa an additional FeSOD type could also be detected. In response
      to salinity, activities of selected SOD, APX, and POD isozymes were increased in
      Lpa, while in Lem plastids the activities of most of SOD and POD isozymes
      decreased. Taken together, it is suggested that plastids play an important role
      in the adaptation of Lpa roots to salinity.

PMID- 11999389
TI  - Simple cryoprotection and cell dissociation techniques for application of the
      comet assay to fresh and frozen rat tissues.
AB  - The single-cell gel electrophoresis (comet) assay has been widely used for
      genotoxicity studies in cell cultures, but its use in solid tissues is hindered
      by problems in isolation of cells and in cryopreservation techniques. Here, we
      used minced liver tissues from rats to compare a homogenization technique for
      isolation of nuclei with a collagenase digestion method (300 units/g liver at 37
      degrees C for 20 min) for isolation of intact cells for subsequent comet assay We
      found that collagenase digestion was preferred to the homogenization technique in
      fresh tissues, but neither method prevented the extensive DNA damage caused by
      cryopreservation (-85 degrees C for 72 h). To minimize this damage, minced liver
      (1.0 g) and kidney (0.5 g) tissues were added to 20 ml of pre-cooled 10% glycerol
      or 10% dimethylsulfoxide (DMSO). We showed that cryoprotection with DMSO (-85
      degrees C for 72 h and 3 weeks), and to a slightly lesser extent with glycerol
      (72 h), followed by collagenase digestion led to satisfactory recovery of liver
      cells with little or no DNA strand breakage. We then used DMSO as a
      cryoprotective agent to optimize the amount of collagenase and its incubation
      time in frozen liver and kidney tissues. We showed that the collagenase digestion
      at 150units/g liver and 300units/g kidney for 10 min produced highest cell
      numbers and minimal DNA strand breaks. We also validated these procedures by
      injection (i.p.) of rats with a known renal carcinogen, ferric nitrilotriacetate
      (Fe/NTA). We showed that Fe/NTA strongly induced DNA strand breaks in both rat
      liver and kidney, while no DNA strand breakage occurred in these tissues from the
      control rats. In addition, no significant differences in strand breaks were found
      between fresh tissues and tissues treated with DMSO during freezing at - 85
      degrees C for 72 h. Thus, the cryoprotection and the cell dissociation techniques
      developed here are satisfactory for preparing both fresh and frozen tissues for
      comet assay. These simple techniques are expected to expand greatly the
      usefulness and efficacy of the assay.

PMID- 11999390
TI  - Scavenging of benzylperoxyl radicals by carotenoids.
AB  - Carotenoids scavenge simple lipid-like alkylperoxyl radicals. However, the rate
      constant is too low to be determined directly and the mechanism is likewise not
      known with certainty [Mortensen, A. and Skibsted, L.H. (1998) FEBS Lett. 426, 392
      396]. It is demonstrated that carotenoids react with peroxyl radicals only
      slightly more reactive than lipidperoxyl radicals neither by electron transfer
      nor by hydrogen atom donation, but by adduct formation. Benzylperoxyl radicals
      are scavenged by the carotenoids beta-carotene and canthaxanthin with a second
      order rate constant of at least 1 x 10(6) M(-1) s(-1) by formation of an adduct
      which decays in a first-order reaction.

PMID- 11999391
TI  - The antioxidant activity of regularly consumed fruit and vegetables reflects
      their phenolic and vitamin C composition.
AB  - Recent studies are emphasising the importance and putative modes of action of
      specific flavonoids as bioactive components of the diet in in vivo and in vitro
      models. Thus, it is important to have a clear idea of the major phenolic families
      of which fruit and vegetables are comprised and the levels contained therein.
      Regularly consumed fruit and vegetables of mixed varieties available on the UK
      market were analysed for the composition of the major individual phenolic
      components. The total phenolic content (applying the Folin assay) and the vitamin
      C levels were also determined. The antioxidant capacities of aqueous/methanolic
      extracts were comparatively assessed using the TEAC (Trolox Equivalent
      Antioxidant Capacity), the FRAP (Ferric Reducing Ability of Plasma) and ORAC
      (Oxygen Radical Absorbance Capacity) assays, which comprise contributions from
      polyphenols, simple phenols and the ascorbate component. The results were
      calculated in terms of 100 g fresh weight (FW) uncooked portion sizes. Fruit and
      vegetables rich in anthocyanins (e.g. strawberry, raspberry and red plum)
      demonstrated the highest antioxidant activities, followed by those rich in
      flavanones (e.g. orange and grapefruit) and flavonols (e.g. onion, leek, spinach
      and green cabbage), while the hydroxycinnamate-rich fruit (e.g. apple, tomato,
      pear and peach) consistently elicited the lower antioxidant activities. The TEAC,
      FRAP and ORAC values for each extract were relatively similar and well-correlated
      with the total phenolic and vitamin C contents. The antioxidant activities (TEAC)
      in terms of 100 g FW uncooked portion size were in the order: strawberry>>
      raspberry = red plum >> red cabbage >>>grapefruit = orange > spinach > broccoli >
      green grape approximately/= onion > green cabbage > pea > apple > cauliflower
      tomato approximately/= peach=leek > banana approximately/= lettuce.

PMID- 11999392
TI  - Silyl linker-based approach to the solid-phase synthesis of Fmoc glycopeptide
      thioesters.
AB  - An efficient solid-phase synthesis of Fmoc (glyco)peptide thioesters is
      described. Fmoc x Ser x OAll and Fmoc x Thr x OAll bound to resin with a silyl
      ether linker were deallylated by Pd(0) catalysis and condensed with thiophenol,
      benzyl mercaptane, and ethyl 3-mercaptopropionate by activation with DCC/HOBt.
      The thioesters were released from the resin either by treatment with CsF-AcOH or
      by acidic hydrolysis. The effectiveness of this silyl linker strategy is further
      demonstrated by the synthesis of more complex (glyco)peptide thioesters 25, 26
      and 27 involving N-->C and C-->N peptide elongation.

PMID- 11999393
TI  - High-level TNF-alpha secretion and macrophage activity with soluble beta-glucans
      from Saccharomyces cerevisiae.
AB  - We have previously reported that water-soluble beta-glucan completely devoid of
      mannoprotein and purified from the yeast cell wall effectively stimulated the
      macrophage function (Biosci. Biotechnol., Biochem., 65, 4, 837-841 (2001)). In
      this present study, to increase the yield of water-soluble beta-glucan, the wild
      type of Sacharomyces cerevisiae, JH, was treated with a combination of UV
      irradiation and laminarinase (endo-beta-(1,3)-glucanase) to yield the
      laminarinase-resistant mutants, JUL1 and JUL3. Water-soluble beta-glucans that
      were free of mannoprotein from JH, JUL1 and JUL3 were purified and their effects
      on TNF-alpha secretion and phagocytosis by macrophages were evaluated. Crude beta
      glucan was first solubilized from the yeast cell wall by alkaline extraction and
      then subjected to an acid treatment. The residual mannoprotein was completely
      removed by DEAE and ConA chromatography. The yield of water-soluble beta-glucan
      in both mutants (JUL1, 5.11%; JUL3, 5.76%) was about 5-fold higher than that of
      the wild type (1.16%). The water-soluble beta-glucan from JH induced TNF-alpha
      secretion slightly more than that from JUL1 or JUL3: TNF-alpha secretion by JH at
      50, 200, 500 microg/ml of beta-glucan was 11-17% more than that by JUL1 or JUL3
      for the same treatment. Beta-glucan from the wild type stimulated phagocytosis
      slightly more than that from the mutants. These mutants could therefore
      effectively produce purified water-soluble beta-glucan with immune activity.

PMID- 11999394
TI  - Identification of an antifreeze lipoprotein from Moraxella sp. of Antarctic
      origin.
AB  - We found six bacteria capable of producing antifreeze protein (AFP) from Ross
      Island, Antarctica. Among these AFP-producing bacteria, strain No. 82 had the
      highest antifreeze activity and was identified as Moraxella sp. The optimum
      temperature and pH for the production of AFP were 5 degrees C and 7.0,
      respectively. After partially purifying the AFP from the culture supernatant
      using 60% saturation of ammonium sulfate, only the 52-kDa protein band (100
      microg/ml) which eluted from SDS-PAGE indicated antifreeze activity by the
      formation of hexagonal crystals. Furthermore, we confirmed that this AFP was a
      lipoprotein by the lipid stain test and treatment with some enzymes and that it
      had no ice-nucleating activity. Also, the N-terminal amino acid sequence of this
      AFP had high similarity with that of outer membrane proteins from Moraxella
      (Branhamella) catarrhalis. This is the first report of AFP-producing bacteria in
      Antarctica and an antifreeze lipoprotein (AFLP) from Moraxella sp.

PMID- 11999395
TI  - Possible antitumor promoters in Spinacia oleracea (spinach) and comparison of
      their contents among cultivars.
AB  - Spinach leaves were found to contain two potent antitumor promoters as detected
      by the activity against tumor promoter-induced Epstein-Barr virus activation. The
      active components were identified as 1-O-alpha-linolenoyl-2-O-(7Z,10Z,13Z)
      hexadecatrienoyl-3-O-beta-D-galactopyranosyl-sn-glycerol and 1,2-di-O-alpha
      linolenoyl-3-O-beta-D-galactopyranosyl-sn-glycerol by spectroscopic data and some
      chemical and enzymatic reactions. Their contents significantly varied with the
      cultivar and with the culture conditions.

PMID- 11999396
TI  - Subulatin, an antioxidic caffeic acid derivative isolated from the in vitro
      cultured liverworts, Jungermannia subulata, Lophocolea heterophylla, and Scapania
      parvitexta.
AB  - The new caffeic acid derivative, subulatin (1), was isolated from in vitro
      cultured liverworts, Jungermannia subulata, Lophocolea heterophylla, and Scapania
      parvitexta. The structure of 1 involved two caffeic acids, D-glucose, and 2
      carboxy-6-(1,2-dihydroxy-ethyl)-4,5-dihydroxy-5,6-dihydro-4H-pyran. The
      connectivity of those and the absolute stereochemistry of 1 were elucidated on
      the basis of spectroscopic evidence. The antioxidative activity of 1 was
      comparable to that of alpha-tocopherol. (2'R)-Phaselic acid (2a) and (-)-9,2''
      epiphylloyl-L-malic acid (4) were also isolated from J. subulata and L.
      heterophylla, respectively. A chiral HPLC analysis of the p-bromobenzoyl-malic
      acids derived from 2a showed that 2a from J. subulata was unusual (+)-trans
      caffeoyl-D-malic acid.

PMID- 11999397
TI  - Molecular cloning and functional expression of D-sorbitol dehydrogenase from
      Gluconobacter suboxydans IF03255, which requires pyrroloquinoline quinone and
      hydrophobic protein SldB for activity development in E. coli.
AB  - The sldA gene that encodes the D-sorbitol dehydrogenase (SLDH) from Gluconobacter
      suboxydans IFO 3255 was cloned and sequenced. It encodes a polypeptide of 740
      residues, which contains a signal sequence of 24 residues. SLDH had 35-37%
      identity to the membrane-bound quinoprotein glucose dehydrogenases (GDHs) from E.
      coli, Gluconobacter oxydans, and Acinetobacter calcoaceticus except the N
      terminal hydrophobic region of GDH. Additionally, the sldB gene located just
      upstream of sldA was found to encode a polypeptide consisting of 126 very
      hydrophobic residues that is similar in sequence to the one-sixth N-terminal
      region of the GDH. For the development of the SLDH activity in E. coli, co
      expression of the sldA and sldB genes and the presence of pyrrloquinolone quinone
      as a co-factor were required.

PMID- 11999398
TI  - Cloning, nucleotide sequencing, and expression in Escherichia coli of the gene
      for formate dehydrogenase of Paracoccus sp. 12-A, a formate-assimilating
      bacterium.
AB  - The gene for the NAD-dependent formate dehydrogenase (FDH) of Paracoccus sp. 12
      A, a formate-assimilating bacterium, was cloned through screening of the genomic
      library with activity staining. The FDH gene included an open reading frame of
      1,200 base pairs, and encoded a protein of 43,757 Da, which had high amino acid
      sequence identity with known FDHs, in particular, with bacterial enzymes such as
      those of Moraxella sp. (86.5%) and Pseudomonas sp. 101 (83.5%). The gene was
      highly expressed in Escherichia coli cells using an expression plasmid with the
      pUC ori and tac promoter. The recombinant enzyme was somewhat inactive in the
      stage of the cell-free extract, but its activity markedly increased with
      purification, in particular, with the step of heat-treatment at 50 degrees C. The
      purified enzyme showed essentially the same properties as the enzyme from the
      original Paracoccus cells.

PMID- 11999399
TI  - Molecular cloning, functional expression, and mutagenesis of cDNA encoding rye
      (Secale cereale) seed chitinase-c.
AB  - We cloned a complete cDNA encoding rye seed chitinase-c, designated RSC-c, by
      rapid amplification of cDNA end and PCR procedures. The cDNA of RSC-c consists of
      1,018 nucleotides and includes an open reading frame encoding a polypeptide of
      266 amino acid residues. A recombinant RSC-c was produced by expression in
      Escherichia coli Origami(DE3) and purified. rRSC-c had almost the same chitinase
      activity toward glycolchitin and antifungal activity against Trichoderma sp. as
      the authentic RSC-c did. RSC-c mutants were subsequently constructed and
      characterized with respect to their chitinase and antifungal activities. Mutation
      of Glu67 to Gln completely abolished the chitinase activity and diminished the
      antifungal activity. Considerable decreases in both activities were observed in
      the mutations of Trp72 and Ser120 to Ala, and Glu89 to Gln. The roles of these
      residues in the catalytic event of RSC-c are discussed.

PMID- 11999400
TI  - Molecular cloning, characterization, and expression analysis of the xynF3 gene
      from Aspergillus oryzae.
AB  - The gene encoding xylanase F3 (xynF3) was isolated from a genomic library of
      Aspergillus oryzae KBN616, used for making shoyu koji. The structural part of
      xynF3 was found to be 1468 bp. The nucleotide sequence of cDNA amplified by RT
      PCR showed that the open reading frame of xynF3 was interrupted by ten short
      introns and encoded 323 amino acids. Direct N-terminal amino acid sequencing
      showed that the precursor of XynF3 had a signal peptide of 22 amino acids. The
      predicted amino acid sequence of XynF3 has strong similarity to other family 10
      xylanases from fungi. The xynF3 gene was successfully overexpressed in A. oryzae
      and the XynF3 was purified. The molecular mass of XynF3 estimated on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis was 32,000. This was almost
      the same as the molecular mass of 32,437 calculated from the deduced amino acid
      sequence. The purified XynF3 showed an optimum activity at pH 5.0 and 58 degrees
      C. It had a Km of 6.5 mg/ml and a Vmax of 435 micromol x min(-1) x mg(-1) when
      birch wood xylan was used as a substrate. Expression of the xynF3 gene was
      analyzed using an Escherichia coli beta-glucuronidase gene as a reporter. The
      result indicated that xynF3 is expressed in the medium containing wheat bran as a
      carbon source.

PMID- 11999401
TI  - Effect of the polyoxyethylene chain length of triton X surfactants on the
      adsolubilization of reconstituted wax model compounds.
AB  - The effect of the surfactant, alpha-[4-(1,1,3,3-tetramethylbutyl) phenyl]-omega
      hydroxypolyoxy-1,2-ethanediyl, on the adsolubilization of cholesterol and/or
      dotriacontane as model compounds of the epicuticular wax of mature tomato
      (Lycopersicon esculentum Mill.) fruit was investigated. Cholesterol as a model
      compound of such triterpenols as alpha- and beta-amyrins was solubilized in a
      concentration-dependent manner above the critical micelle concentration (cmc),
      while non-detectable quantities of the saturated hydrocarbon, dotriacontane, was
      solubilized at any concentration used. However, the surfactants solubilized more
      cholesterol from mixed than single membranes. The surfactants with a shorter
      polyoxyethylene (POE) chain length solubilized greater quantities than those with
      longer POE chains, suggesting that the microenvironment of micelles related to
      the polyoxyethylene moiety had an important effect on surfactant solubilization
      and that the octylphenol moiety must be capable of adsorbing to a specific region
      of the reconstituted membrane like dotriacontane.

PMID- 11999402
TI  - Purification and characterization of membrane-bound malate dehydrogenase from
      Acetobacter sp. SKU 14.
AB  - Membrane-bound NAD(P)-independent malate dehydrogenase (EC 1.1.99.16) was
      purified to homogeneity from the membrane of thermotolerant Acetobacter sp. SKU
      14, an isolate from Thailand. The enzyme was solubilized from the membrane
      fraction of glycerol-grown cells with 1% Triton X-100 in the presence of 0.1 M
      KCl, and purified to homogeneity through steps of column chromatographies on DEAE
      Sephadex A-50 and DEAE-Toyopearl in the presence of 0.1% Triton X-100. The
      purified enzyme showed a single protein band in both native-PAGE and SDS-PAGE.
      The enzyme was a homodimer with a molecular mass of 60 kDa subunit and had
      noncovalently bound FAD as the cofactor. The enzyme was stable over pH 5 and had
      its maximum activity at pH 11.0 when ferricyanide was used as an electron
      acceptor. The enzyme activity was elevated by the addition of ammonium ions. The
      substrate specificity was very strict to only L-malate, of which the apparent Km
      was 10 mM and over 20 compounds involving D-malate were not oxidized by the
      enzyme.

PMID- 11999403
TI  - L-erythrulose production by oxidative fermentation is catalyzed by PQQ-containing
      membrane-bound dehydrogenase.
AB  - Thermotolerant Gluconobacter frateurii CHM 43 was selected for L-erythrulose
      production from mesoerythritol at higher temperatures. Growing cells and the
      membrane fraction of the strain rapidly oxidized mesoerythritol to L-erythrulose
      irreversibly with almost 100% of recovery at 37 degrees C. L-Erythrulose was also
      produced efficiently by the resting cells at 37 degrees C with 85% recovery. The
      enzyme responsible for mesoerythritol oxidation was found to be located in the
      cytoplasmic membrane of the organism. The EDTA-resolved enzyme required PQQ and
      Ca2+ for L-erythrulose formation, suggesting that the enzyme catalyzing meso
      erythritol oxidation was a quinoprotein. Quinoprotein membrane-bound
      mesoerythritol dehydrogenase (QMEDH) was solubilized and purified to homogeneity.
      The purified enzyme showed a single band in SDS-PAGE of which the molecular mass
      corresponded to 80 kDa. The optimum pH of QMEDH was found at pH 5.0. The
      Michaelis constant of the enzyme was found to be 25 mM for meso-erythritol as the
      substrate. QMEDH showed a broad substrate specificity toward C3-C6 sugar alcohols
      in which the erythro form of two hydroxy groups existed adjacent to a primary
      alcohol group. On the other hand, the cytosolic NAD-denpendent meso-erythritol
      dehydrogenase (CMEDH) of the same organism was purified to a crystalline state.
      CMEDH showed a molecular mass of 60 kDa composed of two identical subunits, and
      an apparent sedimentation constant was 3.6 s. CMEDH catalyzed oxidoreduction
      between mesoerythritol and L-erythrulose. The oxidation reaction was observed to
      be reversible in the presence of NAD at alkaline pHs such as 9.0-10.5. L
      Erythrulose reduction was found at pH 6.0 with NADH as coenzyme. Judging from the
      catalytic properties, the NAD-dependent enzyme in the cytosolic fraction was
      regarded as a typical pentitol dehydrogenase of NAD-dependent and the enzyme was
      independent of the oxidative fermentation of L-erythrulose production.

PMID- 11999404
TI  - Enzymatic synthesis of a capsinoid by the acylation of vanillyl alcohol with
      fatty acid derivatives catalyzed by lipases.
AB  - Capsinoids are a novel group of compounds produced by the Capsicum plant. We
      synthesized a capsinoid by the lipase-catalyzed esterification of vanillyl
      alcohol with fatty acid derivatives in an organic solvent. The use of seven out
      of 17 commercially available lipases, especially Novozym 435, was applicable to
      the synthesis of vanillyl nonanoate, a model compound of capsinoids. The yield of
      vanillyl nonanoate under the optimum conditions of 50 mM vanillyl alcohol and 50
      mM methyl nonanoate in 500 microl of dioxane, using 20 mg of Novozym 435 and 50
      mg of 4 A molecular sieves at 25 degrees C, was 86% in 20 h. Several capsinoid
      homologues having various acyl chain lengths (C6-C18) were synthesized at 64-86%
      yields from the corresponding fatty acid methyl ester. The natural capsinoids,
      capsiate and dihydrocapsiate, were obtained by a 400-fold-scale reaction at these
      optimum conditions in 60% and 59% isolated yields, respectively.

PMID- 11999405
TI  - Identification of serine138 residue in the 4-residue segment K135K1361137S138 of
      LukS-I component of Staphylococcus intermedius leukocidin crucial for the LukS-I
      specific function of staphylococcal leukocidin.
AB  - Luk-I produced by Staphylococcus intermedius was found to be a new member of the
      staphylococcal bi-component pore-forming toxin family, in which staphylococcal
      leukocidin, Panton-Valentine leukocidin, and gamma-hemolysin are included. Luk-I
      consists of LukS-I and LukF-I. From the deduced amino acid sequence of LukS-I, a
      4-residue sequence, K135K1361137S138, at the root of the stem region was found to
      be identical with that of the phosphorylated segment of a protein phosphorylated
      by protein kinase A. A mutant of LukS-I (MLSI-SA), in which the Ser138 residue
      was replaced by an alanine residue, was created, purified, and assayed for its
      leukocytolytic and pore-forming activities with LukF-I. Both LukS-I and MLSI-SA
      formed a ring-shaped complex with LukF-I on rabbit erythrocytes and human
      polymorphonuclear leukocytes (HPMNLs) membrane. However, MLSI-SA showed no
      leukocytolytic activity with LukF-I. LukS-I was phosphorylated by protein kinase
      A in the presence of [gamma-32P] ATP in a cell-free system, but MLSI-SA was not
      phosphorylated significantly. A potent and selective inhibitor of protein kinase
      A (N-[2(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89)) showed 50%
      inhibition of the Luk-I-induced cell lysis at 0.5 nM. Thus, it is concluded that
      the phosphorylation of the Ser138 residue in the 4-residue segment
      K135K1361137S138 of LukS-I is important for the leukocytolysis of HPMNLs.

PMID- 11999406
TI  - Amelioration of the salt-stressed root growth of rice and normalization of the
      Na+ distribution between the shoot and root by (S)-alpha-methylbenzyl-2-fluoro-4
      methylphenylurea.
AB  - Optically active alpha-methylbenzyl phenyl ureas (MBPUs) show diverse plant
      physiological properties. Experiments were conducted to evaluate the salt-stress
      response of just-germinated rice seedlings supplemented with the S-enantiomer of
      MBPUs by assessing the growth and Na+ content. This study indicates that S-MBPUs
      served as a unique stress reliever for just-germinated young seedlings of rice
      injured by salinity. NaCl severely affected the root growth of rice seedlings.
      Concomitant treatment with S-MBPUs effectively ameliorated the growth inhibition
      of rice by NaCl. Glycine betaine (GB) did not act as a reliever of the NaCl
      stress. The addition of S-alpha-methylbenzyl 2-fluoro-4-methylphenyl urea (7,
      denoted as S-FM) to the saline medium ameliorated not only the root growth but
      also the protein content and dry weight of roots depending upon its
      concentration. The protein content, Na+ content and growth rate were correlated
      to each other with a positive relationship. The Na+ distribution ratio (S/R(Na+))
      between the shoot and root increased with increasing concentration of NaCl when
      added alone, viz. with increasing growth reduction. A concomitant treatment with
      S-FM (7), however, resulted in the S/R(Na+) value becoming smaller with growth
      amelioration. This indicates that S-FM (7) controlled the translation of Na+ from
      the roots to shoots. S-FM (7) would have influenced some inherent functions
      connected with the Na+ behavior in the rice plant, although details of the
      mechanism for normalization of the S/R(Na+) ratio are still not clear.

PMID- 11999407
TI  - Production of brain-derived neurotrophic factor in Escherichia coli by
      coexpression of Dsb proteins.
AB  - When brain-derived neurotrophic factor (BDNF) is produced in the Escherichia coli
      periplasm, insoluble BDNF proteins with low biological activity and having
      mismatched disulfide linkages are formed. The coexpression of cysteine
      oxidoreductases (DsbA and DsbC) and membrane-bound enzymes (DsbB and DsbD), which
      play an important role in the formation of disulfide bonds in the periplasm, was
      investigated to improve the production of soluble and biologically active BDNF.
      The expression levels of Dsb proteins changed when the growth medium and the Dsb
      expression plasmids were changed, and the production rate of soluble BDNF was
      almost proportional to the expression level of DsbC protein with disulfide
      isomerase activity in the case of a low expression level of BDNF. The rate of
      soluble BDNF production with coexpression of DsbABCD was as high as 35%. These
      results show that coexpression of BDNF and Dsb proteins can effectively increase
      the production of soluble and biologically active BDNF.

PMID- 11999408
TI  - Effects of quantity and quality of dietary protein on the brain polysome profile
      in aged rats.
AB  - The purpose of this study was to determine whether the quantity and quality of
      dietary protein affected the polysome profile of the brain in aged rats. Two
      experiments were done on three groups of aged rats (30 wk) given the diets
      containing 20% casein, 5% casein, or 0% casein (experiment 1), and 20% casein,
      20% gluten, or 20% gelatin (experiment 2) for 10 d. The aggregation in brain
      ribosomes declined with a decrease of quantity and quality of dietary protein
      except in the hippocampus. The RNA concentration (mg RNA/g protein) did not
      differ among the three groups varying the dietary protein in any brain regions.
      The results suggest that the higher quantity and quality of dietary protein
      improves the polysome profile in the brain of aged rats, and that the polysome
      profile is at least partly related to the mechanism by which the dietary protein
      affects brain protein synthesis in aged rats.

PMID- 11999409
TI  - Evoking cytochrome P450 1A activity interferes with apoptosis induced by 3-amino
      1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1) in rat hepatocytes under the ex
      vivo system.
AB  - 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is known as a dietary
      carcinogen and it requires metabolic activation by cytochrome P450 (CYP) 1A
      subfamily to have carcinogenicity. On the other hand, our previous report
      demonstrated that Trp-P-1 induces apoptosis in primary cultured rat hepatocytes,
      but the metabolically activated Trp-P-1 added extracelluarly to hepatocytes did
      not induce apoptosis. In this study, we focused on the intracellular status of
      CYPs and investigated apoptotic events induced by Trp-P-1 using hepatocytes
      isolated from rats treated with three chemical inducers for CYPs. In cultured
      hepatocytes from rats treated with 3-methylchoranthrene, which mainly induces CYP
      1A, Trp-P-1-induced apoptosis was suppressed. In the same cultures, intact Trp-P
      1 was decreased and its metabolites were increased. Phenobarbital and pyridine
      did not affect Trp-P-1-induced apoptosis. These results suggested that evoking
      CYP 1A activity might interfere with apoptosis induced by Trp-P-1 in rat
      hepatocytes under the ex vivo system.

PMID- 11999410
TI  - Subsequent products after antioxidant actions of beta-carotene and alpha
      tocopherol have no Salmonella mutagenicity.
AB  - Beta-carotene and alpha-tocopherol are important antioxidants biologically, but
      whether their oxidized products are toxic or not remains to be discovered. Here,
      we chromatographically separated 5 pure products or isomeric mixtures from
      reaction mixtures of beta-carotene and reactive oxygens, and 17 lipid-radical
      scavenging products of alpha-tocopherol. The products were tested for
      mutagenicity using Salmonella typhimurium TA98, TA100, TA102, and TA104, in the
      presence and absence of S9. None showed mutagenicity against any of the four
      strains, or cytotoxicity that influenced the survival of the bacteria. Lipid
      peroxides have been known to increase the formation of mutagens from dietary
      procarcinogens such as heterocyclic amines. So, we also measured the activity to
      increase 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) mutagenicity. The
      products from beta-carotene and alpha-tocopherol did not increase, but rather
      several of them suppressed, the mutagenicity of Trp-P-2. Thus, the products of
      beta-carotene and alpha-tocopherol formed after the antioxidant actions were not
      genotoxic.

PMID- 11999411
TI  - Deodorizing effects of tea catechins on amines and ammonia.
AB  - Deodorizing effects of tea catechins on amines were examined under alkaline
      conditions to eliminate the neutralization reaction. They showed deodorizing
      activity on ethylamine, but none on dimethylamine or trimethylamine. Deodorizing
      activity on ethylamine was found to be in the order of (-)-epigallocatechin
      gallate > gallic acid > (-)-epigallocatechin (EGC) > (-)-epicatechin gallate >
      ethyl gallate >> (+)-catechin = (-)-epicatechin. Further, reaction products of
      EGC with methylamine, ethylamine, and ammonia were detected by HPLC, indicating
      that a deodorizing reaction other than neutralization occurs. From structural
      analysis of the reaction product with the methylamine isolated as a peracetylated
      derivative, the product was presumed to be methylamine substituted EGC, in which
      the hydroxyl group of EGC at the 4' position is replaced by the methylamino
      group. The same replacement reaction took place in the case of ethylamine and
      ammonia.

PMID- 11999412
TI  - Transepithelial transport of the bioactive tripeptide, Val-Pro-Pro, in human
      intestinal Caco-2 cell monolayers.
AB  - Some of the food-derived tripeptides with angiotensin converting enzyme (ACE)
      inhibitory activity have been reported to be hypotensive after being orally
      administered. The mechanism for the intestinal transport of these tripeptides was
      studied by using monolayer-cultured human intestinal Caco-2 cells which express
      many enterocyte-like functions including the peptide transporter (PepT1)-mediated
      transport system. Val-Pro-Pro, an ACE-inhibitory peptide from fermented milk, was
      used as a model tripeptide. A significant amount of intact Val-Pro-Pro was
      transported across the Caco-2 cell monolayer. This transport was hardly inhibited
      by a competitive substrate for PepT1. Since no intact Val-Pro-Pro was detected in
      the cells, Val-Pro-Pro apically taken by Caco-2 cells via PepT1 was likely to
      have been quickly hydrolyzed by intracellular peptidases, producing free Val and
      Pro. These findings suggest that PepT1-mediated transport was not involved in the
      transepithelial transport of intact Val-Pro-Pro. Paracellular diffusion is
      suggested to have been the main mechanism for the transport of intact Val-Pro-Pro
      across the Caco-2 cell monolayer.

PMID- 11999413
TI  - Degradation pathways of trichloroethylene and 1,1,1-trichloroethane by
      Mycobacterium sp. TA27.
AB  - We analyzed the kinetics and metabolic pathways of trichloroethylene and 1,1,1
      trichloroethane degradation by the ethane-utilizing Mycobacterium sp. TA27. The
      apparent Vmax and Km of trichloroethylene were 9.8 nmol min(-1) mg of cells(-1)
      and 61.9 microM, respectively. The apparent Vmax and Km of 1,1,1-trichloroethane
      were 0.11 nmol min(-1) mg of cells(-1) and 3.1 microM, respectively. 2,2,2
      trichloroethanol, trichloroacetic acid, chloral, and dichloroacetic acid were
      detected as metabolites of trichloroethylene. 2,2,2-trichloroethanol,
      trichloroacetic acid, and dichloroacetic acid were also detected as metabolites
      of 1,1,1-trichloroethane. The amounts of 2,2,2-trichloroethanol, trichloroacetic
      acid, chloral, and dichloroacetic acid derived from the degradation of 3.60
      micromol trichloroethylene were 0.16 micromol (4.4%), 0.11 micromol (3.1%), 0.02
      micromol (0.6%), and 0.02 micromol (0.6%), respectively. The amounts of 2,2,2
      trichloroethanol, trichloroacetic acid and dichloroacetic acid derived from the
      degradation of 1.73 micromol 1,1,1-trichloroethane were 1.48 micromol (85.5%),
      0.22 micromol (12.7%), and 0.02 micromol (1.2%), respectively. More than 90% of
      theoretical total chloride was released in trichloroethylene degradation. Chloral
      and 2,2,2-trichloroethanol were transformed into each other, and were finally
      converted to trichloroacetic acid, and dichloroacetic acid. Trichloroacetic acid
      and dichloroacetic acid were not degraded by strain TA27.

PMID- 11999414
TI  - Molecular cloning of cDNAs encoding ribonuclease-related proteins in Nicotiana
      glutinosa leaves, as induced in response to wounding or to TMV-infection.
AB  - We earlier isolated a cDNA clone (NGR1) encoding a wound-inducible ribonuclease
      (RNase NW) from leaves of Nicotiana glutinosa [Kariu et al. Biosci. Biotechnol.
      Biochem., 62, 1144-1151 (1998)]. In this study, two distinct cDNA clones, NGR2
      and NGR3, encoding proteins with a ribonuclease-related sequence in the N.
      glutinosa leaves, were amplified and sequenced. The nucleotide sequences of NGR2
      and NGR3 consist of 1244 bp and 1069 bp, and have open reading frames encoding
      277 (RNase NGR2) and 236 (RNase NGR3) amino acid residues, respectively. The
      deduced amino acid sequences of the putative RNases NGR2 and NGR3 showed 33% and
      58% amino acid sequence identity, respectively, with that of RNase NW and 32%
      identity with each other. Sequence comparison showed that NGR2 is similar to
      RNase RNS2 (61%) from Arabidopsis thaliana, while NGR3 is related to RNase LX
      (84%) from tomato (Lycopersicon esculentum). RNA gel blot analysis showed that
      the RNase NGR2 gene is constitutively expressed to measurable levels; it is not
      increased by either wounding or TMV infection. In contrast, the expression of the
      NGR3 gene is induced after 48 h upon TMV infection.

PMID- 11999415
TI  - Protective effect of alpha-tocotrienol against free radical-induced impairment of
      erythrocyte deformability.
AB  - Alpha-tocotrienol (alpha-T3) has been suggested to protect cellular membranes
      against free radical damage. This study was done to estimate the effect of alpha
      T3 on free radical-induced impairment of erythrocyte deformability by comparing
      it to alpha-tocopherol (alpha-T). An erythrocyte suspension containing 2,2'
      azobis (2-amidinopropane) dihydrochloride (AAPH) was forced to flow through
      microchannels with an equivalent diameter of 7 microm for measuring erythrocyte
      deformability. A higher concentration of AAPH caused a marked decrease in
      erythrocyte deformability with concomitant increase of membranous lipid
      peroxidation. Treatment of erythrocytes with alpha-T or alpha-T3 suppressed the
      impairment of erythrocyte deformability as well as membranous lipid peroxidation
      and they also increased erythrocyte deformability even in the absence of AAPH. In
      these cases, the protecting effect of alpha-T3 was significantly higher than that
      of alpha-T. We emphasize that higher incorporating activity of alpha-T3 into
      erythrocyte membranes seems to be the most important reason for higher protection
      against erythrocyte oxidation and impairment its deformability.

PMID- 11999416
TI  - Transformation of Aspergillus sp. and Trichoderma reesei using the pyrithiamine
      resistance gene (ptrA) of Aspergillus oryzae.
AB  - A pyrithiamine (PT) resistance gene (ptrA) was cloned from a PT resistant mutant
      of Aspergillus oryzae and was useful as a dominant selectable marker for
      transformation of all A. oryzae wild type strain as well as A. nidulans. For
      further study, we examined whether or not ptrA could be used as the
      transformation marker in other species of filamentous fungi. Two types of
      plasmid, which contain ptrA as a selectable marker, were constructed, and the
      transformation experiments were done with them. One is an integrative plasmid,
      pPTRI, and another is the autonomously replicating plasmid pPTRII, which contains
      AMA1. PT-resistant transformants were obtained in the cases of A. kawachii, A.
      terreus, A. fumigatus, and Trichoderma reesei as hosts with pPTRI and pPTRII.
      Furthermore, a beta-glucuronidase (GUS) gene was introduced into A. kawachii and
      A. fumigatus using pPTRII. Almost all the transformants turned blue on GUS assay
      plates. These results indicate that ptrA can also be used for some other
      filamentous fungi besides A. oryzae and A. nidulans.

PMID- 11999417
TI  - Activation of macrophages and the intestinal immune system by an orally
      administered decoction from cultured mycelia of Cordyceps sinensis.
AB  - The effects of an orally administered hot-water extract (HW) from cultured
      mycelia of Cordyceps sinensis on the activation of macrophages and the intestinal
      immune system were studied in mice. The general composition of HW was 83.9%
      carbohydrate, 11.8% protein, 1.9% lipid and 2.4% ash, and the carbohydrates were
      mainly composed of glucose, mannose, galactose and arabinose (molar ratio of
      1.0:0.8:0.5:0.1). HW stimulated the activation (1.7-fold of the saline control)
      of macrophages and IL-6 production (1.5-fold) at 2.0 g/kg/day. Analyzing the
      culture supernatant of Peyer's patch cells from C3H/HeJ mice that had been fed
      with HW at 1.0 g/kg/day for 7 days indicated that the bone marrow cells had
      significantly proliferated (1.9-fold). In addition, the amounts of GM-CSF and IL
      6 in the culture supernatant of Peyer's patch cells at the same dose were
      significantly increased (1.8-fold and 2.2-fold, respectively). These results
      indicate that an oral administration of HW may modulate IL-6 production by the
      activation of macrophages, and also enhance the secretion of hematopoietic growth
      factors such as GM-CSF and IL-6 from Peyer's patch cells. Since such cytokines as
      GM-CSF and IL-6 from Peyer's patch cells act on the systemic immune system, it
      can be assumed that orally administered HW modulated not only the local but also
      systemic immune system.

PMID- 11999418
TI  - Detoxifying effect of desalinated deep seawater on organotin-poisoned Euglena
      gracilis.
AB  - A Euglena gracilis Z strain was used as a biomarker to examine the detoxifying
      effects of desalinated deep seawater (DDSW) and surface seawater (DSSW) on the
      hazardous chemical, tributyltin chloride (TBTCl). A distinct restoration effect
      on cell motility was observed after incubating with DDSW. The effect was largely
      attributed to magnesium, calcium and silicon that are involved in cell motility
      and morphology.

PMID- 11999419
TI  - Isolation and characterization of the genes encoding two metalloproteases (MprI
      and MprII) from a marine bacterium, Alteromonas sp. strain O-7.
AB  - An extracellular alkaline metalloprotease (MprI) from Alteromonas sp. strain O-7
      was purified and characterized. The molecular mass of the purified enzyme was
      estimated to be 56 kDa by SDS-PAGE. The optimum pH and temperature were pH 10.0
      and 60 degrees C, respectively. The gene (mprI) encoding MprI was cloned and its
      nucleotide sequence was analyzed. The deduced amino acid sequence of MprI showed
      significant similarity to metalloproteases classified into the thermolysin
      family. Furthermore, sequence analysis showed that another metalloprotease
      (MprII)-encoding gene was located downstream from mprI. The deduced amino acid
      sequence of MprII showed high similarity to metalloproteases of the
      aminopeptidase family. Similar repeated C-terminal extensions were found in both
      MprI and MprII.

PMID- 11999420
TI  - Preparation of N-substituted aryl and alkyl carbamates and their inhibitory
      effect on oat seed germination.
AB  - A series of N-substituted aryl and alkyl carbamates (RNHCOOR'; R: aryl, alkyl;
      R': aryl, alkyl) was prepared and screened for inhibitory activity toward the
      germination of oat seeds. The activity of each compound was compared with that of
      chlorpropham (isopropyl 3-chlorocarbanilate). Some of the synthetic carbamates
      possessing the N-(phenylthio)methyl group, PhSCH2NHCOOR', showed inhibitory
      activity close or comparable to that of chlorpropham.

PMID- 11999421
TI  - Use of 13C-labeled glucose for measuring exogenous glucose oxidation in mice.
AB  - The author modified a respiratory gas analyzer to analyze the respiratory 13CO2
      of 12 small laboratory animals all at once. To investigate the practical use of
      this system, mice were orally (OR) or intravenously (i.v.) given glucose
      solutions containing three different amounts of 13C-labeled glucose. Expired
      13CO2 derived from exogenous glucose was detected within 10 minutes after
      administration in OR mice, but about 30 minutes in i.v. mice. The height of the
      peak of 13CO2 expiration was correlated with the administered 13C-glucose mass.

PMID- 11999422
TI  - Molecular cloning of the gene encoding thermostable endo-1,5-alpha-L-arabinase of
      Bacillus thermodenitrificans TS-3 and its expression in Bacillus subtilis.
AB  - The gene that encodes a thermostable endo-arabinase (called ABN-TS) from Bacillus
      thermodenitrificans TS-3 was cloned, sequenced, and expressed in the mesophilic
      B. subtilis. The gene contained an open reading frame consists of 939 bp, which
      encodes 313 amino acids. The deduced amino acid sequence of the enzyme showed 50,
      46, and 36% similarity with endo-arabinase from B. subtilis IFO 3134 (PPase-C),
      Pseudomonas fluorescens (ArbA), and Aspergillus niger (ABNA), respectively. The
      hydrophobic and acidic amino acids making up ABN-TS outnumbered those in PPase-C.
      The gene product expressed in B. subtilis, as the host, had substantially the
      same characteristics, and was stable up to 70 degrees C, and the reaction was
      optimal around 70 degrees C, as well as native ABN-TS.

PMID- 11999423
TI  - Cloning and expression of an alpha-L-arabinofuranosidase gene (stxIV) from
      Streptomyces thermoviolaceus OPC-520, and characterization of the enzyme.
AB  - The gene encoding alpha-L-arabinofuranosidase (STX-IV), located upstream of the
      previously reported stxI gene, was cloned and sequenced. The gene is divergently
      transcribed from the stxI gene, and the two genes are separated by 661
      nucleotides. The stxIV gene consists of a 1,092-bp open reading frame encoding
      363 amino acids. The deduced amino acid sequence of the gene showed that STX-IV
      was an enzyme consisting of only a catalytic domain, and that the enzyme had
      significant similarity with alpha-L-arabinofuranosidases belonging to family 62
      of glycosyl hydrolases. The stxIV gene was expressed in Escherichia coli, and the
      recombinant protein was purified to homogeneity. Arabinoxylan and oat spelt xylan
      were good substrates for STX-IV, however, the enzyme showed a low activity with p
      nitrophenyl alpha-L-arabinofuranoside. The optimum pH and temperature were 5.0
      and 60 degrees C, respectively.

PMID- 11999424
TI  - Effects of storage conditions on the composition of Citrus tamurana Hort. ex
      Tanaka (hyuganatsu) essential oil.
AB  - Compositional changes of Citrus tamurana Hort. ex Tanaka (hyuganatsu) essential
      oil were analyzed after storage for 1, 3, 6, and 9 weeks at -21, 5, 20, and 30
      degrees C. The total amount of oxides increased greatly. The contents of
      monoterpene alcohols and ketones also increased. The total amount of monoterpene
      hydrocarbons was unchanged up to 30 degrees C. However, the contents of myrcene,
      gamma-terpinene, and terpinolene decreased, while there was a considerable
      increase in p-cymene. Among the sesquiterpene hydrocarbons, considerable
      increases in the (-)-cedrene, gamma-elemene, and alpha-humullene contents were
      noted in samples stored at 30 degrees C, and the trans-beta-farnesene content
      decreased during storage. The total content of monoterpene alcohols was increased
      slightly. The content of trans-carveol increased during storage. p-Cymene, trans
      carveol, isopiperitone, and limonene oxide contents increased, while gamma
      terpinene, terpinolene, and citronellal contents decreased significantly during
      storage. The changes of these compounds during storage can serve as a quality
      index for hyuganatsu essential oil.

PMID- 11999425
TI  - Temperature-dependent production of carotovoricin Er and pectin lyase in
      phytopathogenic Erwinia carotovora subsp. carotovora Er.
AB  - The production of pectin lyase (Pnl) and carotovoricin (Ctv), as well as cell
      lysis in the plant-pathogenic bacterium Erwinia carotovora subsp. carotovora Er
      are induced by mitomycin C. Here, Pnl and Ctv production and cell lysis were
      found to be temperature-dependent. The optimal temperature for Pnl production was
      30 degrees C. However, the optimal temperature for both Ctv production and cell
      lysis was 23 degrees C, at which Pnl production was reduced to 47% of the
      maximum. These data suggest the possible existence of novel regulation system(s)
      for the production of Pnl and Ctv, and cell lysis, in addition to the well
      documented regulation system of recA, rdgA, and rdgB genes.

PMID- 11999426
TI  - Isolation and characterization of a cysteine protease of freesia corms.
AB  - A protease, freesia protease (FP)-A, was purified to electrophoretic homogeneity
      from regular freesia (Freesia reflacta) corms in harvest time. The Mr of FP-A was
      estimated to be 24 k by SDS-PAGE. The optimum pH of the enzyme was 8.0 using a
      casein substrate. These enzymes were strongly inhibited by p-chloromercuribenzoic
      acid but not by phenylmethane-sulfonylfluoride and EDTA. These results indicate
      that FP-A belongs to the cysteine proteases. The amino terminal sequence of FP-A
      was similar to that of papain, and the sequences was regarded to the conservative
      residues of cysteine protease. From the hydrolysis of peptidyl-p-NAs, the
      specificity of FP-A was found to be broad. It was thought that FP-A was a new
      protease from freesia corms.

PMID- 11999427
TI  - Comparison of hemolytic activities among strains of Heterocapsa circularisquama
      isolated in various localities in Japan.
AB  - Heterocapsa circularisquama (Dinophyceae), a red tide dinoflagellate, is toxic to
      bivalve molluscs such as the pearl oyster (Pinctada fucata), but no harmful
      effects of this alga on fish have been observed so far. We found that 7 strains
      of H. circularisquama showed hemolytic activities toward rabbit erythrocytes in a
      cell-density dependent manner, but to quite different extents. The strains which
      are known to be highly toxic to bivalves tend to show stronger hemolytic
      activities and vice versa, suggesting that the hemolytic activity is parallel
      with the shellfish toxicity of H. circularisquama. Since the hemolytic assay is
      simple, semiquantitative, and reproducible, this assay is useful not only to
      search for certain toxins responsible for the shellfish toxicity of H.
      circularisquama but also to estimate the potential toxicity of a newly appeared
      strain of H. circularisquama.

PMID- 11999428
TI  - Commensal relationship between a sheath-forming bacterium, Sphaerotilus natans,
      and a sheath-degrading bacterium, Paenibacillus sp.
AB  - Paenibacillus sp. strain TB is capable of degrading the sheath prepared from a
      sheathed bacterium, Sphaerotilus natans. S. natans was able to grow alone on
      casamino acids but strain TB was not. Cocultivation of strain TB and S. natans
      was examined in a medium supplemented with casamino acids as a growth substrate.
      The growth of strain TB was observed when the sheath was supplied to the medium
      or in cocultivation with S. natans. The phospholipid amount reached a maximum
      after 24 h of cocultivation and subsequently kept almost the same level for 96 h.
      The sheath amount also reached a maximum after 24 h and then gradually declined.
      The cell concentration of strain TB increased throughout the cocultivation. By
      competitive PCR targeted for amplification of a part of 16S rDNA, the abundance
      ratio (S. natans/strain TB) of 6.7 was obtained at 72 h. Almost no growth of
      strain TB was detected in a coculture with a sheath-less mutant of S. natans. The
      evidence allows the conclusion that strain TB grew by utilizing the intact sheath
      in coculture with S. natans.

PMID- 11999429
TI  - Kinetic resolutions of indan derivatives using bacteria.
AB  - Racemic indan derivatives have been resolved by the hydrolysis of amide bonds
      using Corynebacterium ammoniagenes IFO12612 to produce (S)-amine and (R)-amides.
      In the kinetic resolution of 1 (N-12-(6-methoxy-indan-1-yl)ethyl]acetamide), it
      was possible to run the reaction to 44% conversion on a 10-g scale, obtaining (S)
      amine 4 ((S)-2-(6-methoxy-indan-1-yl)ethylamine) at >99% enantiomeric excess (ee)
      and (R)-1 at 98% ee.

PMID- 11999430
TI  - Effects of Cys mutation on taurocholic acid transport by mouse ileal and hepatic
      sodium-dependent bile acid transporters.
AB  - All cysteines of mouse ileal and hepatic sodium-dependent bile acid transporters
      (Isbt and Ntcp, respectively) were individually replaced by alanine. Replacement
      of Cys106 in Isbt and Cys96 in Ntcp, which are located closely in alignment,
      decreased taurocholate uptake. Although Cys51 in Isbt is conserved in Ntcp, the
      replacement spoiled Isbt only. Both similarity and difference in the arrangement
      of functional sites are suggested.

PMID- 11999431
TI  - Molecular cloning of the gene encoding a novel beta-N-acetylhexosaminidase from a
      marine bacterium, Alteromonas sp. strain O-7, and characterization of the cloned
      enzyme.
AB  - We have reported that the chitinolytic system of Alteromonas sp. strain O-7
      consists of chitinases (ChiA, ChiB, and ChiC), a chitinase-like enzyme (ChiD),
      beta-N-acetylglucosaminidases (GlcNAcasesA, GlcNAcaseB, and GlcNAcaseC), and a
      novel transglycosylative enzyme (Hex99). The gene encoding a beta-hexosaminidase
      with an unusual substrate specificity (hex86), located upstream of the hex99
      gene, was cloned and sequenced. The gene encoded a protein of 761 amino acids
      with a calculated molecular mass of 86,758 Da. The deduced amino acid sequence of
      Hex86 showed sequence similarity with beta-hexosaminidases belonging to family
      20. The hex86 gene was expressed in Escherichia coli, and the recombinant enzyme
      was purified to homogeneity. The enzyme rapidly cleaved p-nitrophenyl-beta-N
      acetyl-D-glucosaminide and slowly cleaved p-nitrophenyl-beta-N-acetyl-D
      galactosaminide. Unexpectedly, the enzyme did not hydrolyzed chitin
      oligosaccharides under the assay conditions for synthetic glycosides. However,
      after prolonged incubation with excessive quantities of the enzyme, Hex86
      hydrolyzed chitin oligosaccharides. These results indicate that Hex86 is a novel
      enzyme that prefers p-nitrophenyl-beta-N-acetyl-D-glucosaminide to chitin
      oligosaccharides as a substrate.

PMID- 11999432
TI  - High-level expression and characterization of fully active recombinant conger eel
      galectins in Eschericia coli.
AB  - An expression system for recombinant conger eel galectins, congerins I and II,
      were constructed using the pTV 118N plasmid vector and Escherichia coli.
      Recombinant congerins I and II could be obtained in the soluble active form with
      high quantitative yield. Mutation of codons for Val and Leu located in the N
      terminal region of Con I increased the expression efficiency. Purification of
      recombinant proteins were done by only two chromatographical steps from E. coli
      extract. The purified recombinant congerins were found to be almost the same as
      the native ones except for the acetyl group at the N-terminus; that is, they
      showed the same structures and carbohydrate binding activities, suggesting that N
      terminal acetyl groups of congerins were not significant for activity.

PMID- 11999433
TI  - Synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate with recombinant Escherichia
      coli cells expressing (S)-specific secondary alcohol dehydrogenase.
AB  - The synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate ((R)-ECHB) from ethyl 4
      chloroacetoacetate was studied using whole recombinant cells of Escherichia coli
      expressing a secondary alcohol dehydrogenase of Candida parapsilosis. Using 2
      propanol as an energy source to regenerate NADH, the yield of (R)-ECHB reached
      36.6 g/l (more than 99% ee, 95.2% conversion yield) without addition of NADH to
      the reaction mixture.

PMID- 11999434
TI  - Changes in cell morphology and cell-to-cell adhesion induced by extracellular
      Ca2+ in cultured taste bud cells.
AB  - Cell morphology and cell-to-cell adhesion of taste bud cells were significantly
      altered by extracellular Ca2+ during in vitro culture. Under high Ca2+ condition
      (above 0.5 mM), the cells were tightly associated with each other and formed
      packed aggregates. Under low Ca2+ condition (below 0.1 mM), the cells were
      dispersed and had an elongated shape. These two forms were reversible and
      specifically dependent on Ca2+. The results indicate that extracellular Ca2+
      regulates cell shape and cell-to-cell adhesion of taste bud cells.

PMID- 11999435
TI  - Dendritic cells: a specialized complex system of antigen presenting cells.
AB  - The dendritic cell (DC) network is a specialized system for presenting antigen to
      naive or quiescent T cells, and consequently plays a central role in the
      induction of T cell and B cell immunity in vivo. Despite considerable
      achievements in the last ten years, in our understanding of how DC induce and
      regulate immune responses, much remains to be learned about this complex system
      of cells. The history and current status of DC termed "directors of the immune
      system orchestra" is reviewed. The present understanding of DC cell biology,
      function and use, taking into account their complexity is discussed.

PMID- 11999436
TI  - Reproductive productivity measurements in Japanese swine breeding herds.
AB  - To set productivity standards and targets, and investigate inter-relationships
      between key measurements in swine breeding herds, farm productivity measurements
      were analyzed on 87 Japanese commercial farms in 14 prefectures. The 87 herds
      were ranked on the basis of number of pigs weaned per mated female per year
      (PWMFY), and 23 herds in the upper 25th percentile of this ranking were
      designated as high-performing farms. Productivity measurements on the high
      performing farms were compared with values for the remaining farms. The high
      performing farms had shorter farrowing intervals, greater litters per mated
      female per year (LMFY), greater pigs weaned per sow (PWS), and greater mean
      parity of culled sows than the remaining farms (P<0.01). No difference in
      lactation duration was found between the two groups (P>0.10). For both farm
      groups, correlations of key reproductive measurements were determined. Lactation
      duration was not correlated with LMFY, PWS and PWMFY on the high-performing
      farms, while short lactation duration was correlated with greater LMFY and PWMFY
      on the remaining farms (P<0.01). In contrast to lactation duration, farrowing
      interval was correlated with PWS on the high-performing farms, but not on the
      remaining farms. Mean parity of culled sows were correlated to PWS and pigs born
      alive per sow on the high performing farms, but not with any measurements on the
      remaining farms. These results suggest that high-performing farms have used
      different herd management from the remaining farms.

PMID- 11999437
TI  - The effect of heating against Cryptosporidium oocysts.
AB  - The effect of heat treatment was examined against oocysts of Cryptosporidium
      parvum, Cryptosporidium muris and chicken Cryptosporidium sp. isolated in Japan.
      The oocysts of these species were exposed at 50, 55, 60 and 70 degrees C for 5,
      15, 30 and 60 sec in water bath, respectively. To determine the infectivity of
      heated oocysts, the nice and chickens were inoculated with the treated oocysts
      and the oocyst output in the feces after inoculation was examined. In C. parvum
      and chicken Cryptosporidium sp., the oocysts were not detected from mice or
      chickens which were received oocysts heated at 55 degrees C for 30 sec, 60
      degrees C for 15 sec and 70 degrees C for 5 sec. In C. muris, the oocysts were
      not detected from mice which were received oocysts heated at 55 degrees C for 15
      sec, 60 degrees C for 15 sec and 70 degrees C for 5 sec. Consequently, it was
      clarified that the infectivity of Cryptosporidium oocysts to mice and chickens
      was lost by heating at 55 degrees C for 30 sec, 60 degrees C for 15 sec and 70
      degrees C for 5 sec.

PMID- 11999438
TI  - Low expression of cyclin D2 in G2/M-arrested and transformed proliferating
      Balb/3T3 cells.
AB  - At present, the effect of cyclin D2 implicated in cell cycle regulation,
      differentiation, and oncogenic transformation is not fully confirmed. To better
      elucidate the role of cyclin D2 in controling the cell proliferation, cyclin D2
      expression level was determined at the early initiation and promotion stages
      during the in vitro two-stage transformation process of Balb/3T3 A31 cells. N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced G2/M-arrested cells expressed
      low level of cyclin D2 mRNA, while the contact-inhibited nonproliferating cells
      expressed high level of cyclin D2 mRNA. In the transformed proliferating cells at
      the promotion stage, cyclin D2 mRNA was not expressed. These data suggest that
      cyclin D2 expression may be associated with the type of growth arrest and
      nonproliferating state, but not with the cell proliferation and transformation.

PMID- 11999439
TI  - The dynamic expression of extracellular matrix in the bovine endometrium at
      implantation.
AB  - Remodeling of uterine endometrial extracellular matrix (ECM) is pivotal to
      successful implantation and placentation, and has been well described in the
      rodents and humans. However, bovine endometrial ECM remodeling is still vaguely
      defined, especially at the time of implantation. Therefore, this study
      investigated the distribution of four ECMs namely, types I and IV collagen,
      laminin and fibronectin, from days 0 to 30 of gestation in bovine endometrium by
      immunofluorescence microscopy. A change in the distribution pattern of ECMs was
      evident by day 14 of gestation as features at this stage were clearly different
      from those of day 14 of the estrous cycle. The immunoreactivity of type I
      collagen, fibronectin and laminin decreased from day 14 of gestation and was
      obscured by day 24 of gestation. The type I collagen fibers formed were of
      thinner consistency than those of the estrous cycle and showed a coarser meshwork
      within the epithelium sites during the implantation period. In addition, the type
      IV collagen and laminin immunoreactivities of epithelial basement membrane also
      remarkably declined at exactly the same time. By day 30 of gestation, the four
      ECMs had regenerated with the formation of the placentome. In conclusion, this
      study reveals that remodeling of ECM is essential for the successful
      establishment of pregnancy in the bovine.

PMID- 11999440
TI  - An etiological investigation of domestic cats with conjunctivitis and upper
      respiratory tract disease in Japan.
AB  - Chlamydophila felis (C. felis), feline herpesvirus-1 (FHV-1) and feline
      calicivirus (FCV) were detected in 39 (59.1%), 11 (16.7%) and 14 (21.2%) cats
      respectively, from 66 domestic cats presented with conjunctivitis and upper
      respiratory tract disease (URTD) in 9 prefectures of Japan. Dual and multiple
      infections were found in 7 (10.6%) cats with both C. felis and FHV-1, 10 (15.2%)
      cats with both C. felis and FCV, and 1 (1.5%) cat with all three agents. C. felis
      was isolated from 11 (28.2%) of 39 PCR positive cats. Antigenic difference was
      found in a 96 kDa protein of our isolates and Fe/145 strain isolated in USA. In
      conclusion, C. felis is the most common agent of feline conjunctivitis and URTD,
      and the coinfection with C. felis, FHV-1 and FCV are also common in cats in
      Japan.

PMID- 11999441
TI  - The effect of macrophages on the erythrocyte oxidative damage and the
      pathogenesis of anemia in Babesia gibsoni-infected dogs with low parasitemia.
AB  - The role of macrophages in the erythrocyte membrane oxidative damage and the
      pathogenesis of anemia in Babesia gibsoni-infected dogs with low parasitemia were
      investigated. Macrophages derived from peripheral blood monocytes (PBM) from B.
      gibsoni-infected dogs produced significantly higher chemiluminescent responses,
      indicating the release of reactive oxygen intermediates, than those from non
      infected dogs when the cells were subjected to non-specific stimulation with
      phorbol 12-myristate 13-acetate (PMA) and opsonized zymosan (OZ), or infected dog
      erythrocyte membranes opsonized with infected dog serum. These results indicate
      that PBM of B. gibsoni-infected dogs with low parasitemia were highly activated
      compared to those of non-infected dogs. Furthermore, the membrane lipid
      peroxidation of normal dog erythrocytes incubated with PBM from B. gibsoni
      infected dogs was significantly higher (p<0.05) than that of erythrocytes
      incubated with PBM from non-infected dogs when the PBM were stimulated with the
      opsonized membranes. These results suggest that the oxidative damage of
      erythrocytes observed in B. gibsoni-infected dogs with low parasitemia might be
      induced, in part, by reactive oxygen species released from the activated PBM. On
      the other hand, the present study also showed a significant increase (p<0.001) of
      IgG-bound erythrocytes in B. gibsoni-infected dogs compared with such
      erythrocytes in non-infected dogs. The increase of IgG-bound erythrocytes in
      infected dogs might reflect the increase of erythrocytes with oxidative damage
      induced by the infection with B. gibsoni. The results of the present study
      suggest that the increase of IgG-bound erythrocytes in the circulation of
      infected dogs induce a high degree of erythrocyte loss via immunological
      phagocytosis by activated macrophages, resulting in severe anemia in spite of low
      parasitemia.

PMID- 11999442
TI  - Decreased sperm number and motile activity on the F1 offspring maternally exposed
      to butyl p-hydroxybenzoic acid (butyl paraben).
AB  - Butyl p-hydroxybenzoic acid (butyl paraben, BP) is widely used as a preservative
      in food and cosmetic products. Routledge et al showed that BP is weakly
      estrogenic in both in vitro and in vivo (rat uterotrophic) analyses. We
      investigated whether maternal exposures to BP during gestation and lactation
      periods affected the development of the reproductive organs of the F1 offspring.
      Pregnant Sprague-Dawley rats were injected subcutaneously with 100 or 200 mg/kg
      of BP from gestation day (GD) 6 to postnatal day (PND) 20. In the group exposed
      to 200 mg/kg of BP, the proportion of pups born alive and the proportion of pups
      surviving to weaning were decreased. The body weights of female offspring were
      significantly decreased at PND 49. The weights of testes, seminal vesicles and
      prostate glands were significantly decreased in rats exposed to 100 mg/kg of BP
      on PND 49. In contrast, the weights of female reproductive organs were not
      affected by BP. The sperm count and the sperm motile activity in the epididymis
      were significantly decreased at doses of 100 and 200 mg/kg of BP. In accordance
      with the sperm count in the epididymis, the number of round spermatids and
      elongated spermatids in the seminiferous tubule (stage VII) were significantly
      decreased by BP. Testicular expression of estrogen receptor (ER)-alpha and ER
      beta mRNA was significantly increased in 200 mg/kg of BP treated group at PND 90.
      Taken together, these results indicated that maternal exposure of BP might have
      adverse effects on the F1 male offspring.

PMID- 11999443
TI  - Characterization of Staphylococcus intermedius from pigeons, dogs, foxes, mink,
      and horses by pulsed-field gel electrophoresis.
AB  - Staphylococcus intermedius from pigeons, dogs, foxes, mink, and horses, was
      characterized by pulsed-field gel electrophoresis (PFGE) to evaluate the use of
      this typing method for discriminating among strains. SmaI cut the chromosomal DNA
      into 7-13 fragments ranging from approximately 48 kb to 655 kb, with most of the
      detectable fragments being smaller than 172 kb. S. intermedius from various
      animals had a high degree of restriction fragment length polymorphism. Pigeon
      strains have a similar genotype, despite the difference in their isolation area.
      Phage typing indicated that the dog, fox, and mink strains belong to the canine I
      or canine II type. The PFGE method further differentiated the mink strains from
      the dog and fox strains with regard to three fragments between 256 kb and 570 kb.
      As such, genomic DNA fingerprinting by PFGE appears to be an effective technique
      for discriminating S. intermedius strains from various animals. A combination of
      PFGE typing and phage typing would provide more detailed information than the
      single method for ecological investigations of S. intermedius.

PMID- 11999444
TI  - Isolation and species distribution of staphylococci from animal and human skin.
AB  - From April 1999 to December 2000, a survey was made on the distribution of
      Staphylococcus species on the skin of 7 kinds of animals and humans.
      Staphylococci were isolated from 12 (100%) of 12 pigs, 17 (89.5%) of 19 horses,
      30 (100%) of 30 cows, 73 (90.1%) of 81 chickens, 10 (40%) of 25 dogs, 23 (76.7%)
      of 30 laboratory mice, 20 (52.6%) of 38 pigeons, and 80 (88.9%) of 90 human
      beings. The predominant staphylococci isolated from a variety of animal species
      were novobiocin-resistant species, S. xylosus and S. sciuri regardless of the
      animal host species. The novobiocin-resistant species including S. xylosus and S.
      sciuri were only occasionally isolated from human skin. The predominant
      staphylococci found on human skin were novobiocin-sensitive species, S.
      epidermidis (63.8%), followed by S. warneri (28.8%) and S. hominis (13.8%). The
      results suggest that the staphylococcal flora inhabiting animal skin are
      different from those of human skin in regard to the predominant species isolated.
      In this study, we used pulsed-field gel electrophoresis to examine the
      chromosomal polymorphisms of S. epidermidis isolated most frequently from human
      skin. Strains of S. epidermidis showed the greatest genomic diversity in their
      fragment patterns.

PMID- 11999445
TI  - Somatosensory evoked potentials produced by stimulation of the dorsomedial nerves
      innervating the tail in dogs.
AB  - To record the somatosensory evoked potentials (SEPs) produced by stimulation of
      tail nerves and determine the effects of acute compression of the cauda equina on
      SEPs. The subjects were 10 adult Beagles. SEPs were recorded after stimulating
      the dorsomedial nerves (DMN) innervating the tail. The cauda equina was
      compressed using a balloon catheter inserted into the vertebral arch. In SEPs,
      two negative and one positive peak were often observed. The compression of the
      cauda equina caused significant depression of the positive component. The SEPs
      produced by stimulation of the DMN reflect the activities of ascending neuronal
      pathways above the coccygeal spinal segments and may be a useful tool for
      examining cauda equina syndrome.

PMID- 11999446
TI  - Lineage classification of canine inheritable disorders using mitochondrial DNA
      haplotypes.
AB  - To estimate the maternal effects of dog breeds using mitochondrial DNA(mtDNA)
      haplotypes in the dogs with several clinical disorders, 600 base pairs of mtDNA D
      loop region were amplified from 365 dogs and were determined for mtDNA sequences.
      The diversity of the 600-bp sequences was classified into 64 haplotypes,
      including 46 newly discovered haplotypes, and the haplotypes were grouped into
      four clusters I to IV. Lineage analysis using the mtDNA haplotype indicated that
      each dog breed genetically comprises one or a few mtDNA haplotypes. When the
      relationship between genetic background and occurrences of clinical diseases was
      estimated, canine lineage analysis using mtDNA haplotype revealed that the
      disorders distributed in the dominant mtDNA haplotypes of each dog breed, but no
      disorder closely associated with mtDNA haplotypes was detected.

PMID- 11999447
TI  - Malignant melanoma of the eyelid in a red squirrel (Sciurus vulgaris orientis).
AB  - A 6-year-old male red squirrel (Sciurus vulgaris orientis) developed bilateral
      tumors of upper and lower eyelids. The tumors in the left lid recurred despite
      surgical removal. Necropsy revealed metastasis to the lung. The neoplastic cells
      were epithelioid and highly pleomorphic, and only a few cells contained melanin
      granules. Occasionally melanoma cells were immunoreactive for S100, neuron
      specific enolase and vimentin, and a small number of cells for cytokeratin.
      Ultrastructurally, the presence of premelanosomes was confirmed in the cytoplasm.
      Possible presence of cytokeratin-positive neoplastic melanocytes should be taken
      into account when differentiating a nonpigmented epithelioid melanoma from other
      tumors such as anaplastic carcinomas.

PMID- 11999448
TI  - Rumen ciliate faunae of water buffalo (Bubalus bubalis) and goat (Capra hircus)
      in Nepal.
AB  - Rumen ciliate composition of river-type water buffalo and goat in Nepal was
      surveyed. As the result of survey, 13 genera representing 52 species and 20
      formae of the ciliates were identified. Of them 13 genera with 44 species and 9
      formae were found from the water buffalo and 8 genera with 21 species and 12
      formae from the goat. The present paper shows the first report of Hsiungella
      triciliata, Entodinium brevispinum, E. convexum, E. javanicum, E. rectangulatum
      f. rectangulatum, E. rectangulatum f. lobosospinosum, Diplodinium nanum, D.
      psittaceum, D. sinhalicum and Ostracodinium quadrivesiculatum from water buffalo
      and Epidinium ecaudatum f. parvicaudatum from goat.

PMID- 11999449
TI  - Juvenile malignant mesothelioma in a dog.
AB  - An 11-month-old male mixed breed dog was euthanized due to two months history of
      vomiting and anorexia. At necropsy, numerous, multifocal or coalescing, firm,
      protruding nodules, 5 to 40 mm in diameter were scattered throughout the
      mesentery and omentum. Histologically and immunohistochemically, the nodules were
      diagnosed as malignant mesothelioma. Metastasis to the regional mesenteric,
      mediastinal and tracheobronchial lymph nodes were observed.

PMID- 11999450
TI  - Characterization of the 16S-23S rRNA intergenic spacer regions among strains of
      the Fusobacterium necrophorum cluster.
AB  - The 16S-23S rRNA intergenic spacer regions (ISRs) of Fusobacterium necrophorum
      subsp. necrophorum and F. necrophorum subsp. funduliforme were characterized.
      Products of two sizes, about 360 bp (small) and 530 bp (large), were generated by
      PCR amplification from the 16S-23S rRNA ISR of all the strains tested. The large
      and small 16S-23S rRNA ISRs of F. necrophorum exhibited a level of sequence
      similarity of 93.9% to 99.7% and 94.2% to 98.6% homologies within the species,
      respectively. Only the large spacer regions in these bacteria contained one or
      two tRNA genes. F. necrophorum subsp. necrophorum contains the isoleucine and
      alanine tRNA gene, whereas F. necrophorum subsp. funduliforme contains the
      isoleucine tRNA gene.

PMID- 11999451
TI  - Electrocorticographic and histological findings in a Shetland sheepdog with
      intractable epilepsy.
AB  - A Shetland sheepdog with epilepsy refractory to antiepileptic drugs was brought
      to the division of Veterinary Radiology at Nippon Veterinary and Animal Science
      University. Scalp electroencephalography and computed tomography was performed,
      but no abnormality was detected in either examination. To obtain detailed
      information, electrodes were implanted on the dura mater, and the
      electrocorticogram (ECoG) was recorded. In the ECoG, sporadic spikes were
      detected in the left parietal region, suggesting the presence of the epileptic
      focus in this region. After the dog's death, abnormalities of gyri were found in
      the region where spikes were detected in the ECoG. On histopathological
      examination, laminar malacia of the cingulate gyrus was observed. Furthermore, in
      the hippocampus, neuronal loss of pyramidal cells was observed.

PMID- 11999452
TI  - Characterization of monoclonal antibodies against the second-generation schizonts
      of Leucocytozoon caulleryi.
AB  - Monoclonal antibodies (MAbs), R1 and M5, were established against the second
      generation schizont of Leucocytozoon caulleryi (L. caulleryi). Both antibodies
      reacted to membrane and internal structure proteins of the second-generation
      schizont by immunofluorescence microscopy. Molecular weight of the second
      generation schizont (2GS) antigen was analyzed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. At least 40
      protein bands were detected in 2GS antigen by SDS-PAGE under reduced condition
      and ranged from 10 to 270 kDa. MAb R1 reacted to polypeptides of 150-268 kDa in
      2GS antigen, whereas MAb M5 did with that of 66 kDa. Injection with a protein of
      2GS antigen fractionated by affinity chromatography using MAbs R1 and M5
      protected chickens against challenge with sporozoites of L. caulleryi. These
      results suggest that MAbs, R1 and M5, recognize 2GS antigen of L caulleryi.

PMID- 11999453
TI  - Comparison of the 16S-23S rRNA intergenic spacer regions between Fusobacterium
      varium and "Fusobacterium pseudonecrophorum" strains.
AB  - The 16S-23S rRNA intergenic spacer regions (ISRs) of five strains of
      "Fusobacterium pseudonecrophorum" which had been proposed as a new species, were
      compared with those of F. varium ATCC 8501T. All the strains of "F.
      pseudonecrophorum" exhibited of sequence similarities of 97.7% to 100% to the
      strain of F. varium in their 16S-23S rRNA ISR sequences. This indicates that the
      strains of "F. pseudonecrophorum" and the type strain of F. varium are identical
      at the species level.

PMID- 11999454
TI  - Spontaneous complex odontoma in a Sprague-Dawley rat.
AB  - Complex odontoma from a female Sprague-Dawley rat is described
      histopathologically. Necropsy revealed a hard (bony), white mass (3.0 x 3.0 x 2.1
      cm) on the left mandible. Microscopically, the mass consisted of islands or nests
      of epithelial and mesenchymal elements that formed abortive tooth structures. In
      other areas, tooth formation consisted of a pulp cavity lined by layers of
      odontoblasts, dentin, enamel, and ameloblasts. Concerning all features of normal
      tooth formation which was differentiated and mineralized yet completely
      disorganized, the diagnosis of complex odontoma was recommended.

PMID- 11999455
TI  - Effect of smoke inhalation injury on fluid requirement in burn resuscitation.
AB  - The effect of smoke inhalation injury on fluid requirement was assessed
      retrospectively. A total of 131 burn patients were classified into two groups:
      burn patients with smoke inhalation injury (Group IB: 73 patients) and burn
      patients without inhalation injury (Group B: 58 patients). Fluid resuscitation
      was commenced according to the Parkland formula and the infusion rate was
      modified to meet the main resuscitation goal of an hourly urine output of 1.0 to
      2.0 ml/kg. Regression analyses were performed on the volume of fluid administered
      during the initial 24 hours after injury by burn size for each group. The linear
      equations obtained were Y (ml/kg/24 hrs) = 71.0 + 5.08 x %TBSA (Group IB) and Y =
      39.7 + 5.14 x %TBSA (Group B). A substantial effect of inhalation injury on fluid
      requirement was speculated to be reflected in a y intercept difference of about
      30 ml/kg/24 hrs. Thus, an increase in the fluid requirement related to the
      presence of inhalation injury was found to be independent and additional to burn
      injury.

PMID- 11999456
TI  - Results of a home exercise program for patients with osteoporosis resulting from
      neurological disorders.
AB  - There are no studies in the literature on the effect of exercise in reversing
      osteoporosis of the upper extremities for people with neurological disorders. The
      purpose of this study was to explore what conditions respond to a home exercise
      program for the upper extremities. Sixteen patients, divided randomly into
      experimental and control groups, were recruited for this trial for at least one
      year. Both upper extremities of the patients, affected and unaffected, were
      tested pre and post trial with the Hologic QDR for bone area, bone mineral
      content (BMC), bone mineral density (BMD), fat, muscle mass, muscle mass plus
      BMD, total weight, and relative fat content (percent). The home exercise program
      involved the subject squeezing a ball, one hand at a time, 20 times each, three
      times a day, at least three times a week, while sitting with the elbow flexed and
      the arm resting comfortably at the side of the trunk or on an armrest. A
      significant difference (p < 0.02) was found in bone area, BMC, BMD or relative
      fat content between the affected and sound sides both before and after the study,
      although all parameters were much different for each patient. We found a
      statistically significant difference in a change in the bone area for the
      affected upper extremities of the control group, but not of the experimental
      group. Subjective reactions of the subjects were positive. They stated that they
      felt they were improving and contributing to their recovery. Patients with
      Parkinson's disease, but not those with cerebral infarction, seemed to react to
      the exercise with an increase in bone mineral content, although the difference
      was not significant due to the scarce number of subjects. This is a preliminary
      pilot study to help develop further research on what condition is likely to
      respond to exercise for protection against osteoporosis.

PMID- 11999457
TI  - Evaluation of sustained grip strength for a stroke patient with a mild paresis.
AB  - The purpose of this study was to investigate whether a sustained grip strength
      test is workable as an accurate assessment of activity limitation related to
      muscle weakness of the paretic hands of stroke patients with mild pareses. Sixty
      one stroke patients with mild pareses participated in this study. The maximal
      grip strength and an ability to sustain grip strength were examined with the
      Sustained Grip Strength Test. The latter ability was measured by the sustained
      period of the maximal grip strength (a period that exhibited more than 80% of the
      peak force during a six-seconds trial). The activity limitation of squeezing an
      object was evaluated in four ADL tasks, and the difficulties were rated according
      to three scores. We found that there was a significant positive relationship
      between the degree of the task difficulty and the maximal grip strength for
      paretic hands whose sustained period was over three sec, in all four assessments
      (p < 0.05). However, for paretic hands whose sustained period was under three
      sec, no such relationship was found. Consequently, measuring both the maximal
      grip strength and the sustained period was needed to assess accurately an
      activity limitation related to muscle weakness of the paretic hands of stroke
      patients with mild pareses.

PMID- 11999458
TI  - Effects of nicotine chewing gum on UPDRS score and P300 in early-onset
      parkinsonism.
AB  - It has been reported that nicotine shows some beneficial effects on Parkinson's
      disease. The purpose of the present study is to assess the therapeutic effects of
      nicotine chewing gum in patients with early-onset parkinsonism (EOP). The
      subjects were 8 patients with early-onset parkinsonism (male/female = 4/4, mean
      age; 51.3 years). Four out of 8 patients had a history of smoking (smokers). To
      estimate the effects of nicotine gum, the scores on the Unified Parkinson's
      Disease Rating Scale (UPDRS) and auditory event-related potentials (ERPs) were
      studied before and after taking nicotine gum in the EOP patients. In smokers,
      UPDRS scores improved by more than 10% and the P300 latency of auditory ERPs was
      shortened by more than 30 msec. In contrast, nicotine had no remarkable effects
      on UPDRS scores or auditory ERPs in non-smokers. We suggest that nicotine chewing
      gum may be a possible choice for the treatment of patients with EOP, especially
      when they are smokers.

PMID- 11999459
TI  - Circulating blood volume in burn resuscitation.
AB  - Circulating blood volume (CBV) was prospectively measured in patients with almost
      solely smoke inhalation injury (Group I: 10 patients) and in patients with severe
      cutaneous burn (Group B: 6 patients) consecutively until 96 hours after injury,
      to assess the effect of either injury on intravascular volume status by the pulse
      dye-densitometry method. All participants were treated by an ordinary fluid
      regimen based on the Parkland formula with an hourly urine output of 1.0 to 2.0
      ml/kg for the resuscitation endpoint. CBV was also measured in 15 elective
      surgical patients for a control value (76.7+/-9.0 ml/kg). The level of CBV values
      in Group I was low, ranging from 54.4+/-6.9 ml/kg to 59.6+/-6.2 ml/kg (from 70.9%
      to 77.7% of control value), while in Group B from 48.5+/-5.5 ml/kg to 55.6+/-17.3
      ml/kg (from 63.2% to 72.5%) until 72 hours after injury. There was no significant
      difference in CBV values between the two groups throughout the study period. We
      could elucidate the existence and extent of intravascular volume depletion in
      spite of optimal fluid treatment in both solely smoke inhalation injury and
      solely severe cutaneous burn. Almost solely inhalation injury was found to
      decrease CBV to less than that of severe cutaneous burn, which presumably led to
      the increased fluid requirement. Concerning the resuscitation endpoint in early
      burn treatment, this depletion in CBV must be taken in mind. Hourly urine output
      is speculated to be an effective and practical clue to manage a burn patient
      within permissive hypovolemia.

PMID- 11999460
TI  - Guidelines on erectile dysfunction.
AB  - The introduction of new oral therapies has completely changed the diagnostic and
      therapeutic approach to erectile dysfunction. A panel of experts in this field
      have developed guidelines for clinical evaluation and treatment based on the
      review of available scientific information.

PMID- 11999461
TI  - Molecular aspects of bladder cancer III. Prognostic markers of bladder cancer.
AB  - The current pathological and clinical parameters provide important prognostic
      information, yet still have limited ability to predict the true malignant
      potential of most bladder tumors. In the last years, investigation of the basic
      mechanisms involved in carcinogenesis and tumor progression by molecular biology
      has provided a host of markers which are of potential diagnostic or prognostic
      value for bladder carcinoma. These markers may serve as tools for early and
      accurate prediction of tumor recurrence, progression and development of
      metastases and for prediction of response to therapy. The precise prediction of
      tumor biological behavior would facilitate treatment selection for patients who
      may benefit from radical surgical treatment or adjuvant therapy. We provide a
      current, comprehensive review of the literature on bladder tumor markers with a
      special emphasis on their prognostic potential. The literature suggests that
      currently no single marker is able to accurately predict the clinical course of
      bladder tumors and thus would serve as a reliable prognosticator. A combination
      of prognostic markers could predict which superficial tumors need an aggressive
      form of therapy and which invasive tumors require adjuvant therapy. Altogether,
      the most promising markers are, at this point, Ki-67 and p53 expression as well
      as matrixmetalloproteinase complex and angiogenesis.

PMID- 11999462
TI  - Bladder neoplasms after nephroureterectomy: does the surgery of the lower ureter,
      transurethral resection or open surgery, influence the evolution?
AB  - OBJECTIVE: Nephroureterectomy is the treatment of choice for tumors of the upper
      urinary tract (UUTT). In 1952, a modified version of this technique was
      described, involving endoscopic detachment of the ureter followed by
      nephroureterectomy with a single lumbar incision. We reviewed a retrospective
      survey to assess whether UUTT patients treated with nephroureterectomy with no
      prior history of bladder tumor had different rates of incidence or different
      sites of bladder recurrence according to the specific technique employed.
      METHODS: Patients were divided into group A, 87 patients who underwent a double
      incision nephroureterectomy and group B with 58 patients with prior detachment of
      the ureter. In both groups, incidence was calculated for two variables (bladder
      tumor recurrences and homolaterality of such recurrences) and chi-square tested.
      RESULTS: Bladder tumor was diagnosed at follow-up in 39% of patients in group A
      and 34.5% in group B, with no statistically significant difference (N.S.).
      Bladder tumor recurrences were homolateral to UUTT in 50% of group A cases and
      55% of group B cases (N.S.). CONCLUSIONS: Although this is a retrospective survey
      of two asynchronous groups, given the similar nature of the UUTT cases in both
      groups and the fact that no statistically significant differences have been
      found, it is reasonable to conclude that nephroureterectomy with prior endoscopic
      detachment of the ureter is a safe and radical procedure.

PMID- 11999463
TI  - Qualitative and quantitative detection of urinary human complement factor H
      related protein (BTA stat and BTA TRAK) and fragments of cytokeratins 8, 18 (UBC
      rapid and UBC IRMA) as markers for transitional cell carcinoma of the bladder.
AB  - OBJECTIVE: To evaluate the role of BTA stat, BTA TRAK, UBC Rapid, UBC IRMA and
      voided urinary cytology in the detection of bladder transitional cell carcinoma
      (TCC). METHODS: The study included 78 patients with TCC of the bladder (group A),
      62 patients with a history of bladder TCC without tumor recurrence at the time of
      examination (B, control group), 20 patients with other malignancy of the urinary
      tract (C), 38 patients with non-malignant urinary tract diseases (D), 10 patients
      with urinary tract infection (E) and 10 healthy volunteers (F). Except in group
      F, voided urine was collected before cystoscopy or cystectomy. RESULTS: The
      specificity and sensitivity in bladder cancer detection were 87.1 and 74.4%,
      respectively with BTA stat, 79.3 and 48.7%, respectively with UBC Rapid, 100 and
      33.3%, respectively with cytology, 72.6 and 75.6%, respectively with BTA TRAK,
      64.5 and 70.5%, respectively with UBC IRMA. CONCLUSIONS: The BTA stat and BTATRAK
      tests are superior to UBC Rapid, UBC IRMA and urinary cytology in detection of
      bladder TCC. In daily practice however cytology remains the best adjunct to
      cystoscopy because of its high sensitivity in Tis and 100% specificity.
      Cystoscopy cannot be replaced by any of evaluated methods.

PMID- 11999464
TI  - Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in
      prostate cancers: differences between tumours located in the transition zone and
      in the peripheral zone.
AB  - OBJECTIVES: Transition zone (TZ) carcinomas of the prostate are thought to have
      less malignant potential than tumours that arise in the peripheral zone (PZ). It
      is unclear, however, whether this can be put down to anatomical reasons alone, or
      if there are further differences between tumours of both zones. METHODS: We
      examined Gleason scores, proliferation and apoptosis rates, microvessel density
      (MVD), p53 expression and bcl-2 expression in 76 paraffin-embedded radical
      prostatectomy specimens, containing 54 tumour foci in the TZ and 58 tumour foci
      in the PZ, matched for volume. The terminal deoxynucleotidyl transferase mediated
      dUTP-biotin nick end labelling (TUNEL) method was applied to detect apoptotic
      cells. Proliferation, MVD, p53, and bcl-2 were investigated by
      immunohistochemistry. RESULTS: There were significant differences between TZ
      tumours and PZ tumours in terms of the median Gleason scores (5 versus 7; P <
      0.0001), the proliferation rate (3.2% versus 5.2%; P = 0.0003), and the MVD (68.5
      versus 104; P = 0.0002), but the median apoptosis rate was quite similar (0.8%
      versus 0.9%). The p53 and bcl-2 expression were more frequent in PZ cancers as
      compared to TZ carcinomas (11% versus 2% and 27% versus 6%, respectively).
      CONCLUSION: There is evidence for lower Gleason scores as well as lower
      expression of markers related to tumour growth in TZ carcinomas of the prostate,
      which might contribute to a less malignant clinical behaviour as compared to PZ
      cancers.

PMID- 11999465
TI  - Correlation of initial PSA level and biopsy features with PSA-doubling time in
      early stage prostate cancers in Japanese men.
AB  - OBJECTIVE: To distinguish good candidates for watchful waiting from those who
      need immediate treatment in localized prostate cancer. METHODS: Prostate specific
      antigen (PSA)-doubling time (DT) was calculated by a log-linear regression model
      for 78 patients with clinically localized prostate cancer (T1c: 47, T2a: 6, T2b:
      21, and T3: 4) under surveillance. Median observation period was 37.5 months. The
      first 1-year PSA-DT was compared with the overall PSA-DT in 41 patients who had
      been under surveillance for more than 3 years. RESULTS: There was significant
      difference in the PSA-DT distribution between a pooled group of T1c and T2a and a
      group of T2b and T3 patients (median 58.8 versus 33.3 months, P = 0.0052). A
      combination of three parameters consisting of initial PSA level less than 10
      ng/ml, WHO grade 1, one or two positive core per six to eight systematic biopsy
      cores with 50% or less cancer involvement significantly correlated with PSA-DT
      distribution in the T1c plus T2a group (P = 0.0034). The first year assessment of
      PSA-DT was identical to the overall assessment in 48.8%, 2 years or more in
      36.6%, while it was 2 years or less (possibly over-estimated) in 14.6%.
      CONCLUSION: PSA-DT can be predictable to some extent with the initial PSA level
      and biopsy features in early stage prostate cancers. Prospective study is needed
      to clarify whether temporary observation together with PSA-DT estimation is a
      safe strategy and is complementary to clinico-pathological parameters at
      diagnosis.

PMID- 11999466
TI  - Long-term safety and efficacy of a once-daily formulation of alfuzosin 10 mg in
      patients with symptomatic benign prostatic hyperplasia: open-label extension
      study.
AB  - OBJECTIVES: To evaluate the long-term safety and efficacy of a new, once-daily
      (o.d.) prolonged-release formulation of the clinically uroselective alpha1
      blocker, alfuzosin, in patients with symptomatic benign prostatic hyperplasia
      (BPH). METHODS: This is a 9-month open-label extension of a 3-month double-blind,
      placebo-controlled evaluation of alfuzosin 10 mg o.d. and standard alfuzosin 2.5
      mg, three times daily (t.i.d.), administered without dose titration in both
      cases. A total of 311 patients continued in the extension phase and all received
      alfuzosin 10 mg o.d. Efficacy was evaluated in all patients enrolled in the
      extension phase (n = 311). Safety was assessed in all patients exposed to
      alfuzosin, whether in the double-blind or extension phase (n = 360). RESULTS:
      Mean international prostate symptom score (IPSS) improved significantly, from
      17.1 to 9.3 (P < 0.0001), and mean peak flow rate (PFR) (assessed at through
      plasma levels) increased significantly, from 9.1 to 11.3 ml/s (P < 0.0001),
      between baseline (i.e. beginning of the double-blind phase) and the endpoint of
      the extension phase. Quality of life (QOL) index also improved significantly,
      from 3.3 to 2.1 (P < 0.0001). Alfuzosin was well tolerated, with only 16 of 360
      patients (4.4%) reporting adverse events potentially related to alpha-blockade
      (mainly dizziness). Ejaculation disorders were infrequent (0.6%) and did not show
      a relationship to treatment. The incidence of asymptomatic orthostatic
      hypotension was low (2.8%), and no age effect was identified. CONCLUSIONS:
      Alfuzosin 10 mg o.d. provides effective relief from BPH, and clinical benefits
      are maintained up to 12 months. This study also demonstrates the satisfactory
      long-term safety of this formulation, and its safe use even in at-risk
      populations.

PMID- 11999467
TI  - Once-daily, extended-release formulations of antimuscarinic agents in the
      treatment of overactive bladder: a review.
AB  - Overactive bladder (OAB) is a chronic condition that often requires long-term
      treatment to maintain control of symptoms. A range of therapeutic options are
      available; however, antimuscarinic agents form the mainstay of treatment. Of
      these agents, tolterodine and oxybutynin are the most widely used. It is well
      documented that the immediate-release (IR) formulations of these agents have
      equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates
      a more favorable tolerability profile, particularly in terms of the frequency and
      severity of dry mouth. Due to the development of novel drug delivery systems,
      extended-release (ER) formulations of both oxybutynin and tolterodine are now
      available, permitting once-daily dosing. The convenience of once-daily dosing of
      antimuscarinic agents would be expected to improve patient compliance and further
      relieve the symptoms of OAB. Clinical studies with the ER formulations of
      tolterodine and oxybutynin demonstrate potential clinical advantages over their
      respective IR forms in terms of either efficacy or tolerability or both, although
      the therapeutic index of tolterodine ER appears to show a greater advantage over
      its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the
      two ER agents have not been compared directly in a head-to-head clinical study.
      Overall, available clinical data suggest that the newly developed ER formulation
      of tolterodine represents a significant therapeutic advancement in the treatment
      of OAB.

PMID- 11999468
TI  - Efficacy of virtual glasses in audio-visual sexual stimulation during penile
      color duplex Doppler ultrasonography.
AB  - OBJECTIVE: To examine whether audio-visual sexual stimulation (AVSS) with virtual
      glasses is effective in improving the recording of penile hemodynamics during
      penile color duplex Doppler ultrasonography. PATIENTS AND METHODS: A total of 64
      consecutive patients with erectile dysfunction underwent penile color duplex
      Doppler ultrasonography after intracavernosal injection of 10-20 microg
      prostaglandin El and subsequent genital stimulation. AVSS with virtual glasses
      and earphones was applied when peak systolic velocities (PSV) were less than 35
      cm/s or end diastolic velocities (EDV) were more than 5 cm/s. PSV, EDV and the
      resistive index of both cavernosal arteries were continuously monitored. Clinical
      erectile response was assessed with visual inspection and manual palpation.
      RESULTS: AVSS with virtual glasses was performed on 40 of 64 patients. AVSS
      improved the clinical erectile response in 26 (65%) of 40 patients. Doppler
      ultrasonography without AVSS identified 11 (27.5%), 5 (12.5%), and 24 (60%)
      patients with arteriogenic, veno-occlusive, and mixed-type impotence,
      respectively. However, after real-time AVSS 15 (37.5%), 7 (17.5%), 8 (20%), and
      10 (25%) patients demonstrated non-vasculogenic, arteriogenic, veno-occlusive,
      and mixed-type impotence, respectively. Real-time AVSS improved the Doppler wave
      forms in 65% of cases. CONCLUSION: AVSS with virtual glasses improves the
      recording of physiologic erectile response and may be used as a valuable tool
      during penile color duplex Doppler ultrasonography.

PMID- 11999469
TI  - Successful conservative treatment of infected penile prostheses [correction of
      protheses].
AB  - Three patients with postoperative purulent penile prosthesis infection were
      successfully treated without explantation by employing a conservative treatment
      strategy of local and systemic application of clindamycin. Should no evidence of
      systemic infection be obvious, a conservative "local rescue" procedure should be
      initiated before resorting to surgical explantation.

PMID- 11999470
TI  - Value of duplex Doppler ultrasonography in renal colic.
AB  - OBJECTIVES: The aim of our study was to determine the value of duplex Doppler
      ultrasonography (DDU) in the patients' evolution with renal colic. The study of
      the resistive index (RI), difference of the RI (ARI) associated with a DDU
      intravesical recording (ureteral jets) were compared with renographic findings in
      renal colic. PATIENTS AND METHODS: Between October 1998 and January 2001 we
      studied 377 cases with suspected renal colic by intravenous pyelography (IVP),
      grey-scale ultrasonography and DDU with determination of the RI, the difference
      between the RI of ipsilateral and contralateral kidneys (ARI) and the amplitude
      (maximum length of the intravesical ureteral jet), velocity and frequency of the
      urine bolus. We considered normal values RI < or = 0.70 and ARI < or = 0.06. VP
      was used as a referee investigation and the ureteral intravesical jets were
      determined in standard conditions. All patients came to the hospital between 4
      and 12 h after the onset of the renal colic. RESULTS: We found four series of
      patients: 1, acute (complete) obstructed kidney (IVP nonfunctional) and
      dilatation at normal grey-scale, with normal contralateral kidney (n = 153). In
      this series we found RI > 0.70 in 87%, RI > 0.06 in 90% and absent ureteral
      intravesical jet of the obstructed kidney site in 89%; 2, acute (complete)
      obstructed kidney (IVP nonfunctional) without abnormalities at normal grey-scale,
      with normal contralateral kidney (n = 57). In this series we found RI > or = 0.70
      in 73.5%, deltaRI > 0.06 in 82.5% of patients, absent or asymmetric ureteral
      intravesical jet in 80.7% of cases; 3, incomplete obstructed kidney (IVP with
      various degree of ureterohydronephrosis) with normal contralateral kidney (n =
      96). In this series we found RI > or = 0.70 in 58.3% and deltaRI > 0.06 in 64.5%
      of patients, asymmetric ureteral intravesical jets in 74% of cases; 4, normal
      both kidneys normal IVP) were found in 71 cases (18.8%). In this series we found
      RI < 0.70 in 80.2%, deltaRI < or = 0.06 in 89% of cases, normal ureteral
      intravesical jets in 93% of cases. The mean RI was 0.76 (0.05) in 306 obstructed
      kidneys, significantly higher than the mean RI of 0.62 (0.05) in 448 normal
      kidneys (P < 0.001). The ARI in patients with obstruction was significantly
      higher than in patients with normal both kidneys, at 0.08 (0.05) and -0.001
      (0.03), respectively (P < 0.001). The RI was sensitive in 75.5% and specific in
      92.5% and ARI was sensitive in 80.7% and specific in 95.7% (versus IVP,
      considered the referee value). The presence of the intravesical ureteral jets of
      the renal colic side, associated with the values of RI (RI < or = 0.70) and
      deltaRI (deltaRI < or = 0.06), was followed by spontaneous passage of the stones
      in 71% of cases. CONCLUSIONS: Renal DDU and consecutively, intravesical
      evaluation of ureteral jets could detect acute renal obstruction and, as a
      functional investigation, could have a predictive value regarding the ureteral
      stones passage. It could replace the IVP, being a sensitive and highly specific
      test.

PMID- 11999471
TI  - Prolonged hydrodistention of the bladder for symptomatic treatment of
      interstitial cystitis: efficacy at 6 months and 1 year.
AB  - OBJECTIVE: To determine the efficacy of hydrodistention of the bladder for
      symptomatic treatment of interstitial cystitis after 6 months and 1 year of
      follow-up and to identify a predictive factor. METHODS: The study included 65
      consecutive patients (a first retrospective series of 33 and a second prospective
      series of 32) treated by hydrodistention of the bladder for urinary symptoms
      attributed to interstitial cystitis. All experienced pain on bladder filling,
      which was relieved by micturition or bladder voiding, and had more than two
      nocturias. Glomerulations were detected at short hydrodistention during
      cystoscopy. No patients were subject to NIH exclusion criteria. Hydrodistention
      was performed continuously for 3 h without rest intervals under epidural
      anesthesia using a balloon with a pressure equal to the patient's mean arterial
      pressure. Efficacy was defined as the disappearance of pain on bladder filling or
      the persistence of moderate, non-disabling pain for which the patient did not
      request treatment, and a low frequency of nocturia (zero to two times). The
      efficacy period was estimated according to Kaplan-Meier methods for survival
      curves. The second series was used to verify the analytic results of the first
      series. RESULTS: Treatment efficacy was 12/32 (37.7% CI: 20.7-54.3) at 6 months
      and 7/32 (21.9% CI: 7.6-36.2) at 1 year for the first series, and 18/30 (60.0%
      CI: 45.0-75.0) at 6 months and 13/30 (43.3% CI: 25.6-61.1) at 1 year for the
      second series. In both series, results were better for the subgroup of patients
      with a bladder capacity > or = 150 ml during cystometry before distention.
      CONCLUSIONS: This study showed good but transient efficacy in the least developed
      or least severe forms of the disease.

PMID- 11999472
TI  - Complaints of the ageing male based on a representative community study.
AB  - OBJECTIVES: To determine (a) the relationship between physical and somatoform
      complaints, distress and life satisfaction and ageing in the male community and
      (b) their psychosocial determinants. METHODS: Two stratified random samples of
      the German male population (total of 2,182 men) were investigated by standardised
      questionnaires of complaints (MFI-20, GBB), distress (HADS) and life
      satisfaction. RESULTS: When participants were grouped into six age groups (18-30,
      31-40, 41-50, 51-60, 61-70, >70 years), we found a continuous increase of
      physical, mental and general fatigue, and a reduced activity and motivation
      associated with age. Exhaustion, cardiovascular and musculoskeletal complaints
      also increased. This was accompanied by a reduced health satisfaction and
      increased depression scores. Marked increases of certain complaints occurred in
      specific age groups. CONCLUSIONS: Community data provide important reference
      points in evaluating the ageing male. Based on regression analyses we could also
      demonstrate the contribution of psychosocial vulnerability and protective factors
      to the development of age-related symptoms.

PMID- 11999473
TI  - Anatomy of the rectourethralis muscle.
AB  - OBJECTIVES: To define the true anatomic structure of the rectourethralis muscle.
      METHODS: Cross-sectional images of fresh tissues from the Visible Human Data set
      were reviewed. Three-dimensional computer reconstructions of the rectourethralis
      and surrounding structures were generated from these data using a high speed
      computer and imaging software. The structure of rectourethralis was confirmed by
      dissection of fresh cadavers. RESULTS: The rectourethralis arises deep within the
      substance of the smooth muscle of the rectal wall as two limbs of muscle which
      face posterolaterally. These limbs fuse into a single thick muscle which inserts
      into the perineal body. CONCLUSIONS: In contrast to all previous descriptions in
      the literature, the rectourethralis is a Y-shaped muscle which arises within the
      substance of the rectal wall deep to the outer longitudinal smooth muscle. This
      shape is consistent with the muscle's embryologic origin. Knowledge of the
      structure of the rectourethralis muscle will help urologists avoid rectal
      injuries during perineal approaches to the prostate.

PMID- 11999474
TI  - The coupling between point-of-gaze and ball movements in three-ball cascade
      juggling: the effects of expertise, pattern and tempo.
AB  - The relationship between point-of-gaze and ball movements in three-ball juggling
      was examined as a function of expertise, pattern and tempo. Five intermediately
      skilled and five expert jugglers performed the standard and reverse cascade at
      three tempos, while point-of-gaze and ball movements were recorded
      simultaneously. Scaled to the size of the ball patterns, the experts made smaller
      point-of-gaze movements than the intermediates, especially in the horizontal
      direction and in the standard cascade. In both skill groups, point-of-gaze and
      ball movements were often 1 : 1 frequency locked in the horizontal direction,
      whereas in the vertical direction 1 : 2 frequency locking also occurred. In the
      latter direction, the 1 : 1 ratio prevailed in the intermediates and the 1 : 2
      ratio in the experts. In addition, the incidence of the 1 : 1 ratio decreased and
      that of the 1 : 2 ratio increased with increasing tempo. Furthermore, in the
      vertical direction, increasing tempo resulted in a weaker 1 : 1 locking, whereas
      the strength of the 1 : 2 ratio remained unaffected by tempo. In the horizontal
      direction, the strength of the 1 : 1 locking was higher on average in the reverse
      cascade than in the standard cascade. We conclude that expertise in juggling is
      reflected by an overall reduction in the extent to which the balls are visually
      tracked, and that task constraints such as tempo and juggling pattern affect the
      visual search patterns of both expert and intermediate jugglers.

PMID- 11999475
TI  - Head, eye and arm coordination in table tennis.
AB  - The aim of this study was to determine the role of head, eye and arm movements
      during the execution of a table tennis forehand stroke. Three-dimensional
      kinematic analysis of line-of-gaze, arm and ball was used to describe visual and
      motor behaviour. Skilled and less skilled participants returned the ball to cued
      right or left target areas under three levels of temporal constraint: pre-, early
      and late-cue conditions. In the pre- and early-cue conditions, both high and low
      skill participants tracked the ball early in flight and kept gaze stable on a
      location in advance of the ball before ball-bat contact. Skilled participants
      demonstrated an earlier onset of ball tracking and recorded higher performance
      accuracy than less skilled counterparts. The manipulation of cue condition showed
      the limits of adaptation to maintain accuracy on the target. Participants were
      able to accommodate the constraints imposed by the early-cue condition by using a
      shorter quiet eye duration, earlier quiet eye offset and reduced arm velocity at
      contact. In the late-cue condition, modifications to gaze, head and arm movements
      were not sufficient to preserve accuracy. The findings highlight the functional
      coupling between perception and action during time-constrained, goal-directed
      actions.

PMID- 11999476
TI  - Gaze pursuit and arm control of adolescent males diagnosed with attention deficit
      hyperactivity disorder (ADHD) and normal controls: evidence of a dissociation in
      processing visual information of short and long duration.
AB  - Three-dimensional kinematic analysis of line of gaze, arm and ball was used to
      describe the visual and motor behaviour of male adolescents diagnosed with
      attention deficit hyperactivity disorder (ADHD). The ADHD participants were
      tested when both on (ADHD-On) and off (ADHD-Off) their medication and compared to
      age-matched normal controls in a modified table tennis task that required
      tracking the ball and hitting to cued right and left targets. Long-duration
      information was provided by a pre-cue, in which the target was illuminated
      approximately 2 s before the serve, and short-duration information by an early
      cue illuminated about 350 ms after the serve, leaving approximately 500 ms to
      select the target and perform the action. The ADHD groups differed significantly
      from the control group in both the pre-cue and early-cue conditions in being less
      accurate, in having a later onset and duration of pursuit tracking, and a higher
      frequency of gaze on and off the ball. The use of medication significantly
      reduced the gaze frequency of the ADHD participants, but surprisingly this did
      not lead to an increase in pursuit tracking, suggesting a barrier was reached
      beyond which ball flight information could not be processed. The control and ADHD
      groups did not differ in arm movement onset, duration and velocity in the short
      duration early-cue condition; in the long-duration pre-cue condition, however,
      the ADHD group's movement time onset and arm velocity differed significantly from
      controls. The results show that the ADHD groups were able to process short
      duration information without experiencing adverse effects on their motor
      behaviour; however, long-duration information contributed to irregular movement
      control.

PMID- 11999477
TI  - A menage a trois: the eye, the hand and on-line processing.
AB  - This review summarizes research conducted in our laboratories over the past 5
      years aimed at determining the temporal and spatial relationships between eye and
      hand movements and the amount of central processing that must occur before
      performing a manual aiming movement, relative to the amount of processing that is
      done online. All of our research to date points to a two-component model of speed
      accuracy control in manual aiming. Several studies have shown that eye and hand
      movements in manual aiming are inextricably linked both temporally and spatially.
      Typically, the eye arrives in the vicinity of the target first; this coincides
      with peak acceleration of the finger during the initial impulse phase of a
      movement. There is also significant temporal and spatial coupling of the finger,
      elbow and shoulder in aiming, and movements appear to evolve in a proximal-to
      distal fashion. Movements are endpoint driven and variability is reduced with
      distal approximation to the target. This movement control strategy means that
      visual information is not only available for use in modifying responses, but
      there is sufficient time available for its use. In sequential complex aiming
      movements, the use of visual feedback and on-line processing become even more
      important. Practice does not diminish the need for on-line processing; rather,
      its use appears to ensure greater movement efficiency.

PMID- 11999478
TI  - The effects of anxiety and strategic planning on visual search behaviour.
AB  - The past decade has witnessed increased interest in the visual search behaviour
      of athletes. Little is known, however, about the relationship between anxiety and
      eye movements in sport performers or about the extent to which athletes' planned
      and actual visual search strategies correspond. To address these issues, we
      conducted two studies. In Study 1, eight expert female gymnasts were presented
      with three digital slides of a model performing a skill that is known to be
      anxiety-provoking in this sport--namely, the 'back flip' on the beam. By varying
      the height of the beam and the presence or absence of safety mats, the slides
      differed in the amount of anxiety that they elicited vicariously in the viewer.
      In the study, the gymnasts were asked to imagine themselves in the position of
      the depicted model and to describe the anxiety that they felt. As they viewed the
      slides, their eye movements were recorded. As predicted, anxiety was associated
      with an increase in the number of fixations to peripheral areas. In addition, the
      more 'threatening' slides elicited significantly more fixations than the less
      feared images. In Study 2, the plans of 15 equestrian performers (5 expert, 5
      intermediate and 5 novice) were elicited as they engaged in a virtual 'walk'
      around a computerized show-jumping course. Contrary to expectations, the
      congruence between intended and actual search behaviour was not significantly
      greater for expert riders than for the less skilled groups. Also, the fact that
      the top riders allocated more fixations to slides than the less skilled
      performers challenged the prediction that expertise would be associated with
      economy of visual search. Finally, as expected, the expert riders were
      significantly less dependent on the overall 'course plan' than the intermediate
      and novice equestrian performers when inspecting the fences.

PMID- 11999479
TI  - Anxiety, arousal and visual attention: a mechanistic account of performance
      variability.
AB  - Despite extensive research devoted to determining the nature of the relationship
      between stress and performance, there has been little systematic examination of
      the mechanisms underlying this relationship. Recently, researchers have begun to
      empirically address the attentional mechanisms underlying theoretical accounts of
      how stress, anxiety and arousal influence performance. Given the critical role of
      visual attention to sport expertise, this paper focuses primarily on literature
      dealing with how visual cues are differentially identified and processed when
      performers are anxious. Emerging evidence indicates that gaze behaviour
      tendencies are reliably altered when performers are anxious, leading to
      inefficient and often ineffective search strategies. Alterations of these visual
      search indices are addressed in the context of both self-paced and externally
      paced sports events. Recommendations concerning the utility of perceptual
      training programmes and how these training programmes might be used as anxiety
      regulation interventions are discussed. The theoretical implications and
      directions for future research are also addressed.

PMID- 11999480
TI  - Learning from demonstrations: the role of visual search during observational
      learning from video and point-light models.
AB  - In this study, we examined the visual search strategies used during observation
      of video and point-light display models. We also assessed the relative
      effectiveness of video and point-light models in facilitating the learning of
      task outcomes and movement patterns. Twenty-one female novice soccer players were
      divided equally into video, point-light display and no-model (control) groups.
      Participants chipped a soccer ball onto a target area from which radial and
      variable error scores were taken. Kinematic data were also recorded using an opto
      electrical system. Both a pre- and post-test were performed, interspersed with
      three periods of acquisition and observation of the model. A retention test was
      completed 2 days after the post-test. There was a significant main effect for
      test period for outcome accuracy and variability, but observation of a model did
      not facilitate outcome-based learning. Participants observing the models acquired
      a global movement pattern that was closer to that of the model than the controls,
      although they did not acquire the local relations in the movement pattern,
      evidenced by joint range of motion and angle-angle plots. There were no
      significant differences in learning between the point-light display and video
      groups. The point-light display model group used a more selective visual search
      pattern than the video model group, while both groups became more selective with
      successive trials and observation periods. The results are discussed in the
      context of Newell's hierarchy of coordination and control and Scully and Newell's
      visual perception perspective.

PMID- 11999481
TI  - Effect of verbal instructions and image size on visual search strategies in
      basketball free throw shooting.
AB  - We assessed the effects on basketball free throw performance of two types of
      verbal directions with an external attentional focus. Novices (n = 16) were pre
      tested on free throw performance and assigned to two groups of similar ability (n
      = 8 in each). Both groups received verbal instructions with an external focus on
      either movement dynamics (movement form) or movement effects (e.g. ball
      trajectory relative to basket). The participants also observed a skilled model
      performing the task on either a small or large screen monitor, to ascertain the
      effects of visual presentation mode on task performance. After observation of six
      videotaped trials, all participants were given a post-test. Visual search
      patterns were monitored during observation and cross-referenced with performance
      on the pre- and post-test. Group effects were noted for verbal instructions and
      image size on visual search strategies and free throw performance. The 'movement
      effects' group saw a significant improvement in outcome scores between the pre
      test and post-test. These results supported evidence that this group spent more
      viewing time on information outside the body than the 'movement dynamics' group.
      Image size affected both groups equally with more fixations of shorter duration
      when viewing the small screen. The results support the benefits of instructions
      when observing a model with an external focus on movement effects, not dynamics.

PMID- 11999482
TI  - Visual search, anticipation and expertise in soccer goalkeepers.
AB  - We used a novel methodological approach to examine skill-based differences in
      anticipation and visual search behaviour during the penalty kick in soccer.
      Expert and novice goalkeepers were required to move a joystick in response to
      penalty kicks presented on film. The proportion of penalties saved was assessed,
      as well as the frequency and time of initiation of joystick corrections. Visual
      search behaviour was examined using an eye movement registration system. Expert
      goalkeepers were generally more accurate in predicting the direction of the
      penalty kick, waited longer before initiating a response and made fewer
      corrective movements with the joystick. The expert goalkeepers used a more
      efficient search strategy involving fewer fixations of longer duration to less
      disparate areas of the display. The novices spent longer fixating on the trunk,
      arms and hips, whereas the experts found the kicking leg, non-kicking leg and
      ball areas to be more informative, particularly as the moment of foot-ball
      contact approached. No differences in visual search behaviour were observed
      between successful and unsuccessful penalties. The results have implications for
      improving anticipation skill at penalty kicks.

PMID- 11999483
TI  - Introduction to 'social and economic patterning of women's health in a changing
      world.'.

PMID- 11999484
TI  - Gender equity and socioeconomic inequality: a framework for the patterning of
      women's health.
AB  - This paper explores the interrelationship of gender equity and socioeconomic
      inequality and how they affect women's health at the macro- (country) and micro-
      (household and individual) levels. An integrated framework draws theoretical
      perspectives from both approaches and from public health. Determinants of women's
      health in the geopolitical environment include country-specific history and
      geography, policies and services, legal rights, organizations and institutions,
      and structures that shape gender and economic inequality. Culture, norms and
      sanctions at the country and community level, and sociodemographic
      characteristics at the individual level, influence women's productive and
      reproductive roles in the household and workplace. Social capital, roles,
      psychosocial stresses and resources. health services, and behaviors mediate
      social, economic and cultural effects on health outcomes. Inequality between and
      within households contributes to the patterning of women's health. Within the
      framework, relationships may vary depending upon women's lifestage and cohort
      experience. Examples of other relevant theoretical frameworks are discussed. The
      conclusion suggests strategies to improve data, influence policy, and extend
      research to better understand the effect of gender and socioeconomic inequality
      on women's health.

PMID- 11999485
TI  - A generation apart? Gender-related experiences and health in women in early and
      late mid-life.
AB  - There have been a number of critiques in the last few years of the prevailing
      paradigm of research on gender and health, which dominated in the latter part of
      the 20th century. One such criticism has centred on the a historic and
      decontextualised way in which much evidence for gender differences has been used.
      In this paper we aim to show that, even within a relatively confined geographical
      locale over a relatively short period of time, there have been substantial
      changes in gender relations which are likely to have affected the experience,
      opportunities, and attitudes of women born in the early 1930s and early 1950s. We
      illustrate this using data from a study of inequalities in health in Scotland,
      which includes unusually rich longitudinal data on gender, including occupancy
      and experience of gender-related roles, attitudinal data on gender equality, and
      measures of gender role orientation (GRO). These are related to various
      dimensions of health and health behaviour. The data show substantial differences
      in the experiences of two generations of women, who are just 20 years apart in
      age, and a lack of consistency between measures of GRO and health. Whilst on the
      one hand these data suggest the importance of taking more account of the broader
      (social, historical or political) context, the analysis also highlights the
      methodological problems posed.

PMID- 11999486
TI  - The influence of work, household structure, and social, personal and material
      resources on gender differences in health: an analysis of the 1994 Canadian
      National Population Health Survey.
AB  - Data from the 1994 Canadian National Population Health Survey (NPHS) do not
      confirm the widespread assumption that women experience considerably more ill
      health than men. The patterns vary by condition and age and at many ages, the
      health of women and men is more similar than is often assumed. However, we should
      not minimize the gender differences that do exist and in this paper we focus on
      three health problems which are more common among women: distress, migraine and
      arthritis/rheumatism. We consider to what extent work, household structure and
      social, personal and material resources explain these gender differences in
      health. Analysis of the distributions of paid work conditions, household
      circumstances and resources reveal mostly minor differences by gender and
      differences in exposure to these circumstances contribute little to understanding
      gender differences in health. There is also little evidence that greater
      vulnerability is a generalized health response of women to paid and household
      circumstances. We find limited evidence that social, personal and material
      resources are involved in pathways linking work and home circumstances to health
      in ways that differ between the sexes. In conclusion, we consider some reasons
      for the lack of support for our explanatory model: the measures available in the
      NPHS data set which contains little information on the household itself; the
      difficulty of separating 'gender' from the social and material conditions of
      men's and women's lives; and changes in women's and men's roles which may have
      led to a narrowing of differences in health.

PMID- 11999487
TI  - Investigating socio-economic explanations for gender and ethnic inequalities in
      health.
AB  - This paper examines inequalities in the self-reported health of men and women
      from white and minority ethnic groups in the UK using representative data from
      the Health Survey for England, 1993-1996. The results show substantially poorer
      health among all minority ethnic groups compared to whites of working-age. The
      absence of gender inequality in health among white adults contrasts with higher
      morbidity for many minority ethnic women compared to men in the same ethnic
      group. The analysis addresses whether socio-economic inequality is a potential
      explanation for this pattern of health inequality using measures of educational
      level, employment status, occupational social class and material deprivation.
      There are marked socio-economic differences according to gender and ethnic group:
      high morbidity is concentrated among adults who are most socio-economically
      disadvantaged, notably Pakistanis and Bangladeshis. Logistic regression analyses
      show that socio-economic inequality can account for a sizeable proportion of the
      health disadvantage experienced by minority ethnic men and women, but gender
      inequality in minority ethnic health remains after adjusting for socio-economic
      characteristics.

PMID- 11999488
TI  - Women's health status in Poland in the transition to a market economy.
AB  - Since 1989 Poland has been experiencing large-scale social and economic changes
      as a result of the reforms associated with the transition to a market economy.
      This study uses a 1996 Health Survey of over 20,000 women to examine the impact
      of the new socio-economic situation and of women's multiple roles on their health
      at the early stage of transition. We investigated the importance of selected
      economic, socio-demographic and cultural determinants in explaining differences
      in women's health status in Poland, focusing on education level, (un)employment,
      living conditions, marital status, smoking and life style. There are health
      inequalities between men and women in Poland based on life expectancy, chronic
      diseases and health self-assessment. Some of these, especially the large
      differences between life expectancy at working ages, may be attributed to the
      difficult socio-economic situation. The multivariate analysis of women's self
      assessed health and morbidity from selected chronic diseases indicated
      substantial inequalities in health. Together with the behavioural and cultural
      risk factors recognized by medicine, such as obesity, lack of physical exercise
      and smoking, the paper shows the crucial role of economic factors in influencing
      Polish women's health. Women whose financial position is poor are more likely to
      assess their health as less than good, to suffer from respiratory and circulatory
      systems' diseases and report neurotic problems. Other factors, strongly connected
      with the transition process in Poland, which contribute to health problems are
      lack of employment and low educational level, particularly for younger women.
      Women's marital and parental status are also important predictors of some
      categories of health problems; however, their influence varies for women of
      different ages. Our survey also supports the thesis that loneliness in old age,
      defined on the basis of living in a one-person household, may be negatively
      correlated with health status.

PMID- 11999489
TI  - Multiple roles and health among British and Finnish women: the influence of
      socioeconomic circumstances.
AB  - Two contrasting hypotheses have been presented to predict women's health
      variations. The Multiple burden hypothesis predicts that combining a paid job,
      being married, and having children is likely to be detrimental to women's health.
      The multiple attachment hypothesis predicts that multiple roles provide
      attachment to the community, which is likely to be beneficial to women's health.
      These hypotheses are examined in Britain and Finland, which have different
      patterns of women's employment participation. Lone mothers form a critical case,
      since they have fewer attachments and greater burdens, and therefore are expected
      to have poorer health. The socioeconomic position of lone mothers differs in
      Britain and Finland, but in both societies they are likely to have fewer
      attachments. We assess the extent to which health variations between women with
      different family and parental role combinations are because of the differences in
      their socioeconomic status and material circumstances. Comparable surveys from
      Britain and Finland from 1994 were used. Perceived general health and limiting
      long-standing illness were analysed for working age women (20-49 years) by family
      type and employment status. as well as other socioeconomic variables. In both
      countries, women living in two parent families and having children had better
      health than women living in other family types or on their own. Lone mothers form
      a disadvantaged group and showed overall worse health in both countries.
      Adjusting for employment status. education and household income weakened the
      association between family type and poor health. The findings are broadly in
      accordance with the multiple attachment hypothesis. Despite the more generous
      welfare state and high full-time employment among Finnish women, single lone
      mothers report poorer health than other women in Finland as well as in Britain.
      However, in Britain the disadvantaged social position of lone mothers accounts
      for a greater proportion of their poor health than in Finland.

PMID- 11999490
TI  - Combining a job and children: contrasting the health of married and divorced
      women in the Netherlands?
AB  - The research question of this paper is whether the combination of paid employment
      and taking care of children promotes or damages the health of married and
      divorced women in the Netherlands. To answer this question, data are used from
      936 women aged 30-54 years who were either living with a partner (N = 431) or
      divorced and living alone 505). The findings show that combining a job outside
      the home and childcare does not harm women's health, irrespective of the length
      of the working week and the age of the children. In fact, some work-childcare
      combinations are associated with better health. This is true for both married and
      divorced women and especially holds true in the case of a part-time job and
      having older children. Two effects are responsible for the findings: enjoying
      good health enables mothers to work outside the home (selection effect) and
      working outside the home promotes mothers' health (health effect).

PMID- 11999491
TI  - Women's work and health in Iran: a comparison of working and non-working mothers.
AB  - This paper analyses research on the impact of work on mothers' health in Tehran
      (Iran) within a role analytic framework. A survey was conducted of a
      representative sample of working and non-working mothers in Tehran in 1998 (N =
      1065, 710 working mothers, and 355 non-working mothers). Three main explanatory
      factors were examined (socio-demographic, work and work-related, and social-life
      context variables) alongside a range of mental and physical health outcome
      variables. Unlike in the West, where women's paid work is generally associated
      with better health, statistically significant differences between working and non
      working women were not found in Tehran. It is argued that this is a result of the
      counter-balance of the positive and negative factors associated with paid work,
      such as increased stress on one hand and self-esteem on the other. Iranian
      society's particular socio-cultural climate has contributed to this finding, with
      its dominant gender-role ideology; the priority and extra weight placed on
      women's traditional roles as wives and mothers, and the remarkably influential
      impact of husbands' attitudes on women's health.

PMID- 11999492
TI  - Chronic stress and the social patterning of women's health in Canada.
AB  - Existing research on the social patterning of women's health draws attention to
      the significance of social roles and socioeconomic position. Although we know a
      great deal about health differences according to the occupancy of these
      positions, we know a lot less about why such patterns exist. This paper addresses
      this gap by examining the pathways through which social structure is linked to
      health using data from a 1994 Canadian national probability sample of women, aged
      25-64 years. We begin by charting differences in women's self-rated ill-health,
      distress, and reports of long-standing health conditions by socioeconomic
      position and social role occupation. We then assess the extent to which these
      patterns can be understood in relation to the chronic stress arising from these
      social locations. Socioeconomic position, assessed by housing tenure, education,
      and household income, was positively related to health. Employment enhanced
      women's health, as did being currently married and a mother living with children.
      The ongoing stressors that distinguish the experiences of various structural
      locations accounted for some of the health effects of social structure,
      particularly for socioeconomic position. However, chronic stress was largely
      irrelevant to the pathways linking social roles to health. In fact, employed
      women and parents living with children enjoyed better health despite their
      greater stress.

PMID- 11999493
TI  - The importance of low control at work and home on depression and anxiety: do
      these effects vary by gender and social class?
AB  - In this study we consider both a gender model, a model that focuses on the stress
      associated with social roles and conditions in the home environment, and a job
      model, which addresses the stressful characteristics of the work environment, to
      investigate patterns of women's and men's psychological morbidity across
      different social positions. Using data from the Whitehall II Study, a
      longitudinal study of British civil servants, we hypothesise that a lack of
      control in the home and work environments affects depression and anxiety
      differently for women and men and across three social class groups. Both women
      and men with low control either at work or at home had an increased risk of
      developing depression and anxiety. We did not find an interaction between low
      control at home and work. We did, however, find that the risks associated with
      low control either at home or work were not evenly distributed across different
      social positions, measured by employment grade. Women in the lowest or middle
      employment grades who also reported low control at work or home were at most risk
      for depression and anxiety. Men in the middle grade with low work control were at
      risk for depression while those in the lowest grade were at risk for anxiety. Men
      in the middle and highest grades, however, were at greatest risk for both
      outcomes if they reported low control at home. We conclude that, in addition to
      social roles and characteristics of the work environment, future investigations
      of gender inequalities in health incorporate variables associated with control at
      home and social position.

PMID- 11999494
TI  - Socio-economic gradients in psychological distress: a focus on women, social
      roles and work-home characteristics.
AB  - A focus in the literature on determinants of women's health is the cost and
      benefit of occupying multiple roles as employee, spouse, and mother, yet little
      attention has been given to the work and home characteristics of different roles
      for women in paid and unpaid work. The impact of work-home factors on socio
      economic gradients in health has also tended to be overlooked. This paper
      assesses the contribution of work-home factors on socio-economic differences in
      psychological distress among women, using data from the 1958 British birth
      cohort. Outcome measures include psychological distress and social class at age
      33. Work-home measures include: (1) roles--employment, marital status, domestic
      responsibility and parental status (2) work characteristics--psychosocial job
      strain, insecurity, unsocial working hours, and (3) home characteristics youngest
      child's age, total number of children, childcare responsibilities and having an
      older adult in the household (over 70 years). A social gradient in psychological
      distress exists: the odds ratio (OR) for classes IV and V versus. I and II was
      3.02, adjusting for prior psychological distress reduces this to 2.36. Whilst,
      work and home factors were associated separately with distress and social class,
      the combined effect of work and home factors did not account for the class
      gradient in distress. This surprising result therefore implicates factors beyond
      adult social roles examined here in the development of socio-economic gradients.

PMID- 11999495
TI  - How gender affects patterns of social relations and their impact on health: a
      comparison of one or multiple sources of support from "close persons".
AB  - Numerous studies have reported gender differences in the effects of social
      relations on morbidity and mortality. When studying health and associated
      factors, one cannot ignore that sex differences exist and methods that are not
      "gender-fair" may lead to erroneous conclusions. This paper presents a critical
      analysis of the health/social relations association from a measurement
      perspective, including the definitions of people's networks and how they differ
      by gender. Findings from the Whitehall II Study of Civil Servants illustrate that
      women report more close persons in their primary networks, and are less likely to
      nominate their spouse as the closest person, but both men and women report the
      same proportion of women among their four closest persons. Women have a wider
      range of sources of emotional support. To date, most epidemiological studies have
      habitually analysed support provided by the closest person or confidant(e). We
      compared the health effects of social support when measured for the closest
      person only and when information from up to four close persons was incorporated
      into a weighted index. Information from up to four close persons offered a more
      accurate portrayal of support exchanged, and gender differences were attenuated,
      if not eliminated, when this support index was used to predict physical and
      psychological health.

PMID- 11999496
TI  - Place and personal circumstances in a multilevel account of women's long-term
      illness.
AB  - This paper investigates geographical variations in women's reports of limiting
      long-term illness in terms of individual inequalities and the contribution of
      area characteristics among wards and county districts. We use multilevel
      modelling of linked census data from the Office for National Statistics
      Longitudinal Study for England and Wales. We follow a random sample of 76.374
      women aged between 16 and 45 at the time of the 1971 Census for 20 years to
      observe their reported limiting long-term illness (LLTI) at the 1991 Census. Car
      and home ownership were useful markers of social and material advantage,
      apparently protecting against the risk of reporting LLTI. Migration into the
      South-East region appeared beneficial, but otherwise there was little difference
      between those who moved home and those who did not. Differences between county
      districts persist after adjustment for individual circumstances (education and
      ethnicity), but almost all of these differences are explained by the social
      profile of wards in these areas. Geographical differences in LLTI are not,
      therefore, entirely explained by the distribution of individual characteristics:
      a woman with the same history may face a different risk of illness in different
      kinds of area. For women, the social composition of the locality (using the ward
      as a proxy) is more relevant than the broader economic and industrial
      classification of the surrounding county district, which is more important for
      health inequalities among men.

PMID- 11999497
TI  - Charting a course for the future of women's health in the United States:
      concepts, findings and recommendations.
AB  - The JHU Women's and Children's Health Policy Center, with the federal Maternal
      and Child Health Bureau, undertook a review of the health of women in the United
      States and invited experts to develop recommendations on health policy, programs,
      practices and research. The review included published research, program reviews,
      and policy reports on women's physical health, mental health, and health
      behaviors, and on the effects of health services, systems and financing on their
      health. Based on trends in age, ethnic background, education, labor-force
      participation, marriage and childbearing among women, the results of the reviews,
      and the experts' consultation, several recommendations were made for a forward
      looking agenda. They included the need: (1) to focus broadly on women's health,
      not just during pregnancy; (2) for comprehensive, integrated programs and
      services addressing women's unique needs; (3) for integrated programs and
      services across the lifespan; (4) for better provider training about women's
      unique health needs, the differential effects of particular problems on them, and
      the consequences of chronic health problems heretofore considered primarily male
      problems; (5) to eliminate social policies that single out women, particularly
      pregnant women, for punitive actions; (6) to promote social policies that ensure
      economic security for women; and (7) for vigorous public health leadership to
      shape the women's health agenda, recognizing the social and economic context of
      their lives. The social and economic trends among women in the US and the
      recommendations for a women's health agenda have relevance to other developed
      countries as well.

PMID- 11999498
TI  - Task orientated nursing in a tuberculosis control programme in South Africa:
      where does it come from and what keeps it going?
AB  - Task oriented nursing is associated with traditional hospital ward organisational
      practice. This paper describes task orientation in a tuberculosis control
      programme which forms part of the public health system in Cape Town, South
      Africa. Task oriented practice is illustrated with clinical data from a focused
      ethnography on the work of nurses in a tuberculosis control programme. The
      origins of task orientation are traced to the colonial history of nursing in
      South Africa. The authors explore both the explicit and more functional reasons
      for maintaining task orientation, as well as the implicit and mostly unconscious
      socially structured defences which contribute to the continuation of this form of
      practice. Unless attention is given to the complexities of this phenomenon,
      initiatives to change task oriented practice may continue to fail.

PMID- 11999499
TI  - Communicative competence in the delivery of bad news.
AB  - Grounded in the Cegala and Waldron (Communication Studies 43 (1992) 105) model of
      communicative competence, the present study applied the McNeilis (Health
      Communication 13 (2001) 5) provider-patient coding scheme to video tapes of 3rd
      year medical students delivering bad news to a standardized patient. The goal of
      the study was to understand the specific communicative moves that are associated
      with perceptions of competence during bad news delivery. The coding scheme
      assesses Content, Acknowledgment Tokens, Interruptions, Alignment, and Function
      of the message. Naive observers also evaluated the tapes on several items,
      assessing empathy and communicative effectiveness. Nonmedical talk was the most
      common type of content, followed by discussion of the current health problem.
      Neither acknowledgment tokens nor interruptions were frequent. The most common
      function of a message was a closed question, followed by explanations,
      assertions, and open questions. Summing across the functions indicated that
      information giving was the nost common behavior. The perceivers' data showed
      fairly neutral assessments of the medical students--they were generally not
      evaluated very positively, although they were not disliked. Regression analyses
      indicated numerous specific communicative behaviors that were associated with
      judgments of competence. Statements falling into the Nonspecific Content category
      were associated with more positive perceptions, while relational statements,
      moderately closed questions, solicited answers, expansions, restatements,
      assertions, explanations, open questions, bracketing, and small talk as well as
      information verifying, seeking, and giving (summed functions) led to more
      negative perceptions. The results indicate that the delivery of bad news requires
      communicative moves that differ from other kinds of medical communication.
      Depending on the results of future analyses of this topic health are providers
      may be well advised to focus little of their communication information seeking,
      giving, or verifying during the initial lab news delivery consultation, but
      rather to save most communication information for a follow-up scheduled shortly
      afterwards.

PMID- 11999500
TI  - Networks of nomads: negotiating access to health resources among pastoralist
      women in Chad.
AB  - Health resources among pastoralist groups are strongly gendered. While certain
      types of health resources fall within the female domain (home-based treatment,
      caring and supportive roles, and knowledge surrounding particular reproductive
      conditions) access to most outside health practitioners, treatments and knowledge
      is controlled largely by men. For pastoralist women, this means that actions
      taken during illness episodes depend largely on the nature and quality of social
      support systems available, and on their ability to mobilise them effectively.
      These support systems include husband and other affines, male kin, and networks
      of female kin and friends. Factors such as position within domestic and wider
      social units, as well as life cycle, affect women's ability to access and
      mobilise these different support systems for their health needs. However,
      seasonal mobility interacts with gender and social support systems in complex
      ways that profoundly influence women's access to health resources. Most
      literature on nomadic peoples and health focuses on the physical barriers posed
      by spatial mobility to accessing health resources. However, it is suggested here
      that, for pastoralist women in Chad, the spatial fluidity of social networks
      might be a more important consideration. At certain times of the year women enjoy
      relatively easy access to a large range of extended kin and other social
      contacts, while at other times, when people are very dispersed, options become
      much more limited, often resulting in illness treatment being delayed. Mobility
      should not, though, be seen purely as a constraint. It can also be an
      opportunity, increasing the potential geographical and social resource base with
      regard to health for women.

PMID- 11999501
TI  - Homeless "squeegee kids": food insecurity and daily survival.
AB  - Current knowledge about food insecurity in North America is largely based on
      research with low-income households. Much less is known about the food
      experiences of homeless people, a group who are particularly vulnerable to food
      insecurity. This study explored the food experiences of street youth, one of the
      fastest growing segments of the homeless population in Canada. To gain an in
      depth understanding of food insecurity within the context of daily life,
      ethnographic research was undertaken with street youth at one inner-city drop-in
      centre in Toronto, Canada. Results of this study reveal that street youth's
      access to food was precarious amidst the instability and chaos of street life.
      The day-to-day lives of the street youth encountered in this study were
      characterized by a constant struggle to find safe, secure shelter, generate
      income, and obtain sufficient food. In this context, food was a precious
      commodity. Food access was inextricably linked to and contingent upon conditions
      of health, shelter, and income. Food access was precarious since everyday food
      sources purchased food and charitable food assistance were ultimately insecure.
      "Squeegeeing" (washing car windows), the primary source of income for youth in
      the study, was dependent on the weather, political and public will, and youth's
      physical health, and thus did not generate enough money to continuously meet
      basic food needs. Charitable food assistance was considered poor quality and was
      associated with food sickness. The often unsavoury atmosphere of charitable food
      programmes, their locations, capacity, and idiosyncratic rules, policies, and
      hours of operation also affected access. Findings from this study extend the
      current understanding of food insecurity to homeless youth and offer insight into
      current responses to hunger and homelessness.

PMID- 11999502
TI  - Birth order and mortality: a life-long follow-up of 14,200 boys and girls born in
      early 20th century Sweden.
AB  - The present study examines the sex-specific patterns of mortality by birth order
      in four stages of the life-course, using Poisson and logistic regression
      analysis. The main question posed is whether there is any continuing social
      effect of birth order when (a) biological factors at birth, (b) other social
      factors at birth and (c) socio-economic circumstances in adulthood are adjusted
      for. The analyses are based on the Uppsala Birth Cohort Study consisting of all
      14,192 boys and girls who were born alive at the Uppsala Academic Hospital in
      Sweden during the period 1915-9. The results showed that all-cause mortality
      differed according to birth order in all of the four studied age intervals when
      birth year, mother's age, birth weight, gestational age, diseases of mother,
      diseases of the infant, social class and mother's marital status at the time of
      childbirth were adjusted for. The general tendency was for laterborn siblings,
      particularly girls women, to demonstrate a higher mortality risk than firstborn
      children. However, in the oldest age group (55-80 years) the previously
      significant association between birth order and male mortality became
      insignificant when adult socio-economic circumstances were controlled for. This
      indicates that the long-term influence of childhood birth order position on
      mortality is partly mediated by adult social class, education and income. The
      concluding section of the paper notes that laterborn children, and especially
      girls, were a disadvantaged group in early 20th century Sweden. Thus, for the
      subjects in the present study, the childhood social conditions linked to birth
      order position seem to have had consequences for these individuals' health and
      survival that extend over the whole life-course.

PMID- 11999503
TI  - Factors associated with unintended pregnancy in Yamagata, Japan.
AB  - Data on unintended pregnancy are scarce in Japan. The purpose of this study is to
      examine the association of sociodemographic, reproductive, and other health
      behavioral factors with unintended pregnancy. A survey was conducted from May
      through November 1999 in Yamagata, Japan. We distributed anonymous self
      administered questionnaires to cervical and breast cancer screening participants
      aged 35-49 years. There were 564 eligible women, and the number of respondents
      was 421 (74.6%). The proportion of women who had experienced unintended pregnancy
      was 46.2%, and 40.1% of them had repeated experiences. Among 312 pre-menopausal
      married women who did not want to become pregnant, 15.4% were not using any
      contraception. Factors that were significantly associated with the experience of
      unintended pregnancy were age of husband being 4 or more years older [Odds ratio
      (OR) = 1.83], and age at initiation of sexual intercourse (OR = 1.86) and
      marriage during teens (OR = 11.14). Analysis of 1255 pregnancies that the
      subjects had experienced showed that 51.2% and 25.9% of mistimed and unwanted
      pregnancies occurred as a result of no contraceptive use, and 39.5% and 71.1% of
      these ended in abortions. The number of past unintended pregnancies was
      significantly (p < 0.001) correlated with the number of pregnancies (r(s) =
      0.49), live births 0.20) and abortions (r(s) = 0.63). This is the first
      epidemiological study in Japan to examine factors associated with unintended
      pregnancy, and also contraceptive use and pregnancy outcome for each of the
      unintended pregnancy women had experienced. Unintended pregnancy is not a rare
      event among our target population, and many unintended pregnancies leading to
      abortion could be prevented by effective contraceptive use. Results suggest that
      Yamagata's family planning strategies need to target both the younger and older
      generations, and address the role of men. A woman's pregnancy history reflecting
      her past experience of unintended pregnancy could be used as an indicator for
      recognizing the woman's need for appropriate contraceptive counseling for the
      prevention of repeated unintended pregnancies.

PMID- 11999504
TI  - Balancing rigour and acceptability: the use of HIV incidence to evaluate a
      community-based randomised trial in rural Uganda.
AB  - Recent debate about the evaluation of community based, HIV/AIDS behavioural
      interventions has focused on the appropriateness of the randomised controlled
      trial (RCT) design, and the difficulty of obtaining reliable outcome measures. A
      community based HIV AIDS behavioural change RCT, recently conducted in rural
      Uganda, used HIV incidence as the principal outcome measure. This paper examines
      the acceptability of the trial from the community perspective. It asks whether,
      in a rural African setting, it is possible to implement a scientifically rigorous
      evaluation without compromising acceptability of the trial to the community.
      Opinions of the trial held by community members working as trial field workers
      were collected by semi-structured interview (n = 37), and focus group discussions
      (4) Community opinions of the trial were ascertained through 10 focus groups. For
      both field workers and the community, the sero-survey was more salient than the
      intervention, and the source of many rumours and disputes. Despite intensive
      mobilisation and close monitoring of field workers, it was impossible to ensure
      the veracity of explanations about the survey at ground level, and to protect
      each individual from coercion. The community expected a reward in return on their
      blood. Although the introduction of incentives at the final survey round
      increased the acceptability of the trial, they not only created jealousies and
      tensions, but also led to expectations of greater rewards in future. We conclude
      that RCTs in poor, rural communities are feasible, but the challenges involved
      should not be underestimated. Obtaining community support for the trial,
      respecting established hierarchies, and close supervision of field workers are
      all essential, but even then, controversies should be anticipated. There is an
      urgent need for relevant guidelines to help researchers navigate the complex
      ethical issues involved.

PMID- 11999505
TI  - Treading the path of least resistance: HIV/AIDS and social inequalities a South
      African case study.
AB  - This paper outlines aspects of the HIV/AIDS epidemic scenario and the
      complexities associated with it. It reveals the socio-epidemiological patterns of
      the epidemic and in doing so identifies the populations with the greatest and
      fastest growing rates of infection. From the data presented it is evident that
      the pattern of HIV/AIDS in developing countries in sub-Saharan Africa in
      particular is unique. The pattern emerging in South Africa follows closely. The
      features of this pattern are as follows: the epidemic is mainly a heterosexual
      epidemic, the rates of infection in the general population are very high and the
      percentage of HIV-positive women is greater than men. An additional unique
      feature is the young age of onset of infection for women. These data demonstrate
      the need to focus our attention on young African women and the factors
      underpinning their predicament. In order to understand their position we examine
      the long standing relationship between social inequalities and health in general
      and further invoke the concepts of vulnerability and social capital to shed light
      on the position of women in the epidemic. Within the constraints of limited and
      problematic statistical data, the paper argues that a mixture and complex
      interaction of material, social, cultural and behavioural factors shape the
      nature, process and outcome of the epidemic in South Africa. It concludes with
      recommendations for the way forward.

PMID- 11999506
TI  - Participating in decisions about treatment: overt parent pressure for antibiotic
      medication in pediatric encounters.
AB  - This article examines how parents and pediatricians negotiate antibiotic
      prescribing decisions in cases where parents overtly advocate this medication.
      Using the methodology of conversation analysis, this paper examines audio and
      videotaped acute care pediatric encounters and discusses four primary ways in
      which parents raise antibiotics in pediatric encounters. These formulations vary
      in their directness with indirect formulations being more common. The article
      argues that both parents and physicians are oriented to antibiotics as negotiable
      in and through their interaction. Finally, in contrast with existing research,
      this study suggests that overtly advocating for antibiotic treatment is
      relatively unusual; future research will need to incorporate an understanding of
      the effect of both explicit and implicit ways parents communicate pressure for
      prescription treatment.

PMID- 11999507
TI  - Reflections and recommendations on research ethics in developing countries.
AB  - The debate on the ethics of international clinical research involving
      collaboration with developing countries has achieved a high profile in recent
      years. Informed consent and universal standards have been most intensively
      debated. Exploitation and lack of adequate attention to justice in the
      distribution of risks/harm and benefits to individuals and communities have to a
      lesser extent been addressed. The global context in which these debates are
      taking place, and some of the less obvious implications for research ethics and
      for health are discussed here to broaden understanding of the complexity of the
      debate. A wider role is proposed for research ethics committees, one that
      includes an educational component and some responsibility for audit. It is
      proposed that new ways of thinking are needed about the role of research ethics
      in promoting moral progress in the research endeavour and improving global
      health.

PMID- 11999508
TI  - Commentary: biomedical research, trade policy and international health: beyond
      medical ethics.

PMID- 11999509
TI  - Multi-charged oligonucleotide ion formation in sonic spray ionization.
AB  - An oligonucleotide tends to release hydrogen atoms from a phosphoric acid group
      and to form negative ions that can be detected by mass spectrometry. Usually,
      with a solution-spray based ionization technique, the negative ions are present
      in different charge states. Ion formation for the nucleotide is quite complicated
      and is easily influenced by matrix and other constituents in a sample solution,
      as well as by the operating parameters for a mass spectrometer. In this work, we
      studied oligonucleotide ion formation by using an ion trap mass spectrometer
      combined with a sonic spray ionization (SSI) source. An oligonucleotide with 20
      bases was measured. Effects from contaminants and parameters affecting the ion
      production, such as a high voltage applied to the ionization source and sample
      solution-flow rate, were investigated. Our results showed that an ion with about
      one charge for every three bases was most abundant. However, the signal intensity
      and the mass spectrum pattern were sensitive to the matrix and operating
      parameters. One of the reasons for such sensitivity is that there are various ion
      states for an oligonucleotide. Any change in the matrix or an operating parameter
      may shift the balances between the ion states. Adding Tris, or
      (hydroxymethyl)aminomethane, enhanced the signal intensity of the oligonucleotide
      and promoted formation of the oligonucleotide ion with higher charges, while
      adding acetic acid favored the ions with lower charges, compared with that
      obtained in the medium without adding Tris and acetic acid. The effects on
      charged droplets and chemical enhancement were investigated. The mechanism for
      oligonucleotide ion formation is discussed.

PMID- 11999510
TI  - Interaction of bis(ethylene)tin(bis(salicylidene)ethylenediamine) with DNA.
AB  - The fluorescence spectral characteristics and interaction of
      bis(ethylene)tin(bis(salicylidene)ethylenediamine) [Et2Sn(salen)] with DNA are
      described. The polarity of the solvent has a strong effect on the fluorescence
      characteristics of Et2Sn(salen). Et2Sn(salen) bound to DNA showed a marked
      decrease in the fluorescence intensity with a bathochromic shift of the
      excitation and emission peaks. A hypochromism in the UV absorption spectra was
      also observed. KI quenching and competitive binding to DNA between Et2Sn(salen)
      and ethidium bromide (EB) were studied in connection with other experimental
      observations to show that the interactive model between Et2Sn(salen) and DNA is
      an intercalative one. The pH and salt effect on the fluorescence properties was
      also investigated. The intrinsic binding constant was estimated to be 1.071 x
      10(5) mol L(-1) in base pairs and the binding site number is 1.98, respectively.
      A linear relationship between F/F0 and the concentration of calf thymus DNA
      covers 5.1 x 10(-6) - 2.41 x 10(-4) mol L(-1), which can be utilized for
      determining traces of calf thymus DNA with a detection limit of 1.1 x 10(-7) mol
      L(-1) in base pairs.

PMID- 11999511
TI  - Rapid diagnosis of M. tuberculosis using a piezoelectric immunosensor.
AB  - A piezoelectric immunosensor was developed for detecting Mycobacteria
      Tuberculosis (M. TB). Protein A was modified onto a silver-coated piezoelectric
      quartz-crystal sensor. Antibodies could be bond onto the crystal surface in an
      ordered orientation through protein A. An impendence analyzer was employed to
      record the admittance-frequency curve. The experimental results showed a
      successful and less-rigid bonding of protein A and antibodies. Compared with
      other traditional detection methods of TB, the method suggested in this paper was
      sensitive, selective and effective. The nonspecific response was limited by using
      control antibody-rabbit anti-honey bee venom (anti-HBV). A glycine-HCI buffer
      solution (pH = 2.4) was used to release antibodies from a crystal coated with
      protein A, and 0.5 mg/mL anti-TB was used to remove TB from a crystal that was
      bonded by an antibody. Good reusability was exhibited. Spike samples of sputum
      and saliva from normal people with and without adding M. tuberculosis were
      diagnosed using the proposed method. Good results were obtained.

PMID- 11999512
TI  - A novel piezoelectric biosensor for the detection of phytohormone beta-indole
      acetic acid.
AB  - A novel piezoelectric immunosensor has been developed for the determination of
      beta-indole acetic acid (IAA) in dilute solutions. The detection is based on
      competitive immunoreaction between a hapten (IAA) and an antigen (IAA-BSA, hapten
      protein conjugation) bound to an anti-IAA antibody, immobilized on a quartz
      crystal microbalance (QCM). The frequency change (y) of the sensor caused by
      antigen is linearly related to the logarithm of the concentration of IAA (x) in
      the range of 0.5 ng/ml - 5 microg/ml with a regression equation of the form y = 
      23x + 151 (r = 0.9937).

PMID- 11999513
TI  - Investigation of the chemico-physical characteristics of the active components in
      the Chinese herb Gastrodia elata Bl. by capillary zone electrophoresis.
AB  - A CE method for investigating the chemico-physical characteristics of the active
      components of low molecular weight in Gastrodia elata Bl. is described. First,
      the dissociation constants of five active components were determined based on the
      relation between the effective mobility of the solutes and the buffer pH value.
      Second, an equation that describes the relation of the migration time and the
      molecular weight was developed and used to predict the migration order and to
      calculate the electroosmotic velocity. The results predicted by theory agreed
      well with that from experiments.

PMID- 11999514
TI  - Electrochemical behavior of thiamine on a self-assembled gold electrode and its
      square-wave voltammetric determination in pharmaceutical preparations.
AB  - The electrochemical behavior of thiamine on a self-assembled electrode of L
      cysteine (Cys/SAM/Au) has been investigated and Cys/SAM/Au can be used to detect
      thiamine using square-wave voltammetry (SWV). At pH 11.40 Britton-Robinson
      buffer, thiamine exhibits a well-defined anodic peak on Cys/SAM/Au. Under the
      optimized conditions, the anodic peak current of SWV was linear with the content
      of thiamine in the range of 1.1 x 10(-8) - 2.2 x 10(-6) mol/L; the detection
      limit was 5.5 x 10(-9) mol/L. The method was successfully applied to the
      determination of thiamine in pharmaceutical preparations.

PMID- 11999515
TI  - Selective determination of tryptophan by using a carbon paste electrode modified
      with an overoxidized polypyrrole film.
AB  - We report on the selective determination of tryptophan, using a carbon paste
      electrode coated with an overoxidized polypyrrole film. Out of 21 protein amino
      acids, only tryptophan and tyrosine exhibited an oxidative voltammetric response
      with this electrode. Tryptophan, which was preferentially concentrated to the
      electrode under an open circuit condition, was determined by the stripping
      voltammetric technique with a linear response range of 10-100 microM. For the
      determination of 10 microM tryptophan, interference from a 15-fold excess of
      tyrosine gave an positive error of 6%, while the other amino acids did not
      exhibit any detectable interference.

PMID- 11999516
TI  - Glycosylated metalloporphyrins as neutral carriers for PVC membrane electrodes.
AB  - In this paper, the synthesis of a novel ionophore, chloro[5,10,15,20-tetrakis[2
      (2,3,4,6-tetraacetyl-beta-D-glucopyranosyl)-1-O-phenyl]porphinato]manganese
      (MnT(o-glu)PPCl), and its application as a neutral carrier for a PVC membrane
      electrode are described. The MnT(o-glu)PPCl-based PVC membrane electrode shows a
      potentiometric responses to SCN- over a concentration range of 3.4 x 10(-7) - 1.0
      x 10(-1) mol L(-1) with a Nernstian slope and a response time of 20 s. The
      electrode exhibits an anti-Hofmeister selectivity toward SCN- with respect to
      common coexisting anions. As active materials, MnT(o-glu)PPCl shows better
      selectivity toward SCN- than chloro(tetraphenylporphinato)manganese (MnTPPCl).
      The effect of the electrode membrane compositions has been studied and the
      experimental conditions were optimized. The electrode was applied to the
      determination of SCN- in body fluids with satisfactory results.

PMID- 11999517
TI  - Differential pulse polarographic determination of uranium(VI) in complex
      materials after adsorption of its trifluoroethylxanthate cetyltrimethylammonium
      ion-associated complex on naphthalene adsorbent.
AB  - Uranium(VI) is adsorbed as a uranium trifluoroethylxanthate (TFEX)
      cetyltrimethylammonium (CTMA) ion-pair complex on microcrystalline naphthalene
      quantitatively in the pH range 4.2 - 7.0. Without cetyltrimethylammonium as the
      counter ion, the adsorption is hardly 70%. The metal has been desorbed with HCI
      and determined with a differential pulse polarograph. Uranium can alternatively
      be quantitatively adsorbed on TFEX-CTMA-naphthalene adsorbent packed in a column
      at a flow rate of 1 - 5 ml/min and determined similarly. A well-defined peak has
      been obtained in this medium at -0.20 V versus a saturated calomel electrode.
      Cyclic voltammetry, differential pulse polarography and D.C. polarography studies
      indicate that uranium has been reduced irreversibly under these conditions. The
      detection limit is 0.30 microg/ml at the minimum instrumental settings (signal-to
      noise ratio of 2) (with a preconcentration factor of 10, the detection limit
      would be 30 ng/ml for uranium when the volume in the cell is 15 ml). However if
      the volume in the cell is 5 ml, it would have been 10 ng/ml with a
      preconcentration factor of 30. Linearity is maintained in a concentration range
      of 0.5 - 19.0 microg/ml (2.1 - 79.83 x 10(-9) M) with a correlation factor of
      0.9994 and a relative standard deviation of +/-1.1% (in this case 7.5 microg may
      be concentrated from 150 ml of the aqueous sample where its concentration is as
      low as 50 ng/ml). Various parameters, such as the effect of the pH, volume of the
      aqueous phase, flow rate and the interference of a large number of metal ions and
      anions on the determination of uranium, have been studied in detail to optimize
      the conditions for its trace determination in various complex materials, like
      alloys, coal fly ash, biological, synthetic, and waste-water samples.

PMID- 11999518
TI  - A rapid spectrophotometric method for the determination of molybdenum in
      industrial, environmental, biological and soil samples using 5,7-dibromo-8
      hydroxyquinoline.
AB  - A very simple, ultra-sensitive and highly selective non-extractive
      spectrophotometric method for the determination of trace amount of molybdenum(VI)
      using 5,7-dibromo-8-hydroxyquinoline (DBHQ) has been developed. 5,7-Dibromo-8
      hydroxyquinoline reacts in a slightly acidic solution (0.05 - 1.0 M H2SO4) with
      molybdenum(VI) to give a deep greenish-yellow chelate which has an absorption
      maximum at 401 nm. The reaction is instantaneous and the absorbance remains
      stable for over 24 h. The average molar absorption coefficient and Sandell's
      sensitivity were found to be 4.13 x 10(3) L mol(-1) cm(-1) and 7 ng cm(-2) of
      molybdenum(VI), respectively. Linear calibration graphs were obtained for 0.1 -
      50 microg mL(-1) of molybdenum(VI). The stoichiometric composition of the chelate
      is 1:3 (Mo:DBHQ). A large excess of over 50 cations, anions and some common
      complexing agents (e.g. EDTA, oxalate, citrate, phosphate, thiourea, SCN-) do not
      interfere with the determination. The method was successfully used in the
      determination of molybdenum in several Standard Reference Materials (alloys,
      steels and waters) as well as in some environmental waters (inland and surface),
      biological samples (human blood and urine), soil samples, solution containing
      both molybdenum(V) and molybdenum(VI) and complex synthetic mixtures. The method
      has high precision and accuracy (S = +/-0.01 for 0.5 microg mL(-1)).

PMID- 11999519
TI  - LC/MS studies on characterization and determination of N,N'
      ethylenebisdithiocarbamate fungicides in environmental water samples.
AB  - Liquid chromatography/mass spectrometry (LC/MS) has been applied to analyze N,N'
      ethylenebisdithiocarbamate fungicides (EBDCs: manzeb, maneb and zineb) in
      environmental water samples. The EBDCs that are zinc and/or manganese salts are
      transformed into readily water-soluble sodium salts by adding an alkaline EDTA
      solution. The N,N'-ethylenebisdithiocarbamate anion is extracted into chloroform
      hexane (3:1) as an ion pair with tetrabutylammonium, and then S-alkylated with
      methyl iodide. The extraction and derivatization are carried out at room
      temperature. The derivatized ethylenebisdithiocarbamic acid dimethyl ester is
      introduced into an LC/MS equipped with a negative ion electrospray ionization
      interface. Identification of the compound is performed with the specific quasi
      molecular ion, and the quantitative analyses are carried out using the peak
      areas. The average recoveries and coefficients of variation of EBDCs at sub-ppb
      level are 79.1% and 29.3% (n = 6), respectively. The limit of detection based on
      standard deviation of 0.043 microg/L for manzeb is achieved.

PMID- 11999520
TI  - Quantitative analysis of triphenylboron in environmental water samples by liquid
      chromatography/mass spectrometry.
AB  - Liquid chromatography/mass spectrometry (LC/MS) has been applied to the analysis
      of triphenylboron, which has been produced as a substitute for organotin
      compounds, in water. Although commercial triphenylboron compounds are produced as
      pyridinyl complexes, the chemical form in water is supposed to be mainly
      triphenylboron after liberating pyridine. The triphenylborons were extracted from
      water with an Empore C18 extraction disk under acidic condition, and the extracts
      were introduced directly into a liquid chromatograph-mass spectrometer equipped
      with a negative ion electrospray ionization interface. Identification of the
      compounds was performed with specific ions produced from the triphenylboron, and
      a quantitative analysis was carried out using the peak areas. The average
      recoveries from distilled water, seawater and river water at 0.30 ng/ml were
      92.3, 100 and 85.3%, respectively. A detection limit of 0.023 ng/ml for
      triphenylboron was achieved.

PMID- 11999521
TI  - Detection of Ni2+ by a dimethylglyoxime probe using attenuated total-reflection
      infrared spectroscopy.
AB  - A new analytical approach for the detection of Ni2+ utilizing an attenuated total
      reflection (ATR) technique is discussed in this paper. Nickel detection was
      accomplished on a silicon ATR parallelogram crystal uniformly coated by a ca. 1.5
      microm Nafion film embedded with dimethylglyoxime (DMG) probe molecules. The
      detection of Ni2+ is based on the appearance of a unique infrared absorption peak
      at 1572 cm(-1) that corresponds to the C=N stretching mode in the nickel
      dimethylglyoximate, Ni(DMG)2, complex. The suitable operational pH range for the
      nickel infrared sensor is between 6 - 8. High alkalinity in the sample solution
      causes a leaching of Ni(DMG)2. The detection limit of the nickel infrared sensor
      is 1 ppm in a sample solution of pH = 8. Interference studies revealed that Cu2+
      could compete with Ni2+ for the DMG sites in the Nafion matrix. The new nickel
      detection methodology can be potentially utilized, after further improvement, in
      field analysis to locate hot spots contaminated with a high ppm of Ni2+.

PMID- 11999522
TI  - Langmuir aggregation of Nile blue and safranine T on sodium
      dodecylbenzenesulfonate surface and its application to quantitative determination
      of anionic detergent.
AB  - We studied the interaction of sodium dodecylbenzenesulfonate (SDBS) with Nile
      Blue (NB) and Safranine T (ST) by a spectral correction technique. The
      aggregations of NB and ST on an SDBS surface obeyed Langmuir isothermal
      adsorption. The adsorption ratios of NB and ST to SDBS were both 0.5, and the
      adsorption constants of the aggregates were 1.80 x 10(5) and 9.49 x 10(4). The
      aggregations were applied to the quantitative determination of anion detergent in
      samples; the recovery of SDBS was between 90.3 and 106% together with an RSD of
      3.78%.

PMID- 11999523
TI  - Photochemical ion receptor based on a structurally distorted ruthenium(II)
      complex having a crown-ether moiety at the 3,3'-positions on the 2,2'-bipyridine
      ligand.
AB  - Ru(bpy)2(CE-bpy)2+ was prepared where bpy and CE-bpy were 2,2'-bipyridine and bpy
      having a crown-ether moiety at the 3,3'-positions, respectively. Although
      Ru(bpy)2(CE-bpy)2+ showed only very weak emission in acetonitrile, recognition of
      Na+, Li+, or K+ by the crown-ether moiety in CE-bpy resulted in increases in both
      the emission intensity and the lifetime of the complex, demonstrating that it
      acted as a photoreceptor. The results were discussed in terms of a steric
      hindrance between the 3,3'-substituents on CE-bpy and structural changes in both
      CE-bpy and the complex upon ion recognition, as studied by variable-temperature
      1H-NMR and steady-state/dynamic emission spectroscopy of the complex.

PMID- 11999524
TI  - Evaluation of angiotensin I converting enzyme inhibitory activity by an FIA
      combined with biosensors.

PMID- 11999526
TI  - Ethylammonium-selective membrane electrode using p-tert-butylcalix[6]arene
      derivatives.

PMID- 11999525
TI  - Effects of polyols, pH and electrolyte concentrations in TBE buffer on separation
      of double strand DNA fragments by capillary electrophoresis.

PMID- 11999527
TI  - Origin of trace organic contaminants adsorbed on the surface of silicon wafers in
      a manufacturing line.

PMID- 11999528
TI  - Rapid analysis of a triterpenoid saponin mixture from plant extracts by
      electrospray ionization multi-stage tandem mass spectrometry (ESI-MSI).

PMID- 11999529
TI  - Determination of the distribution coefficients of phenol derivatives and others
      based on a volume ratiometry coupled with a shake-flask method.

PMID- 11999530
TI  - Comparison of gamma-ray spectrometry and delayed neutron counting for
      determination of uranium.

PMID- 11999532
TI  - Crystal structure of a symmetrical heterotrinuclear NiII-MnII-NiII complex:
      bis[(N,N'-dimethylformamide) (mu-acetato) [mu-N,N'-bis(salicylidene)-2-hydroxy
      1,3-propanediamine]nickel(II)]manganese(II).

PMID- 11999531
TI  - Crystal structure of 8-chloroandrographolide triacetate.

PMID- 11999533
TI  - Crystal structure of 1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one-4-[(1E)
      (aminomethylidenyl)]-5'-hydroxy-benzo-15-crown-5.

PMID- 11999534
TI  - Crystal structure of N,N,N',N'-tetramethyl-1,4,10,13-tetraoxa-7,16
      diazacyclooctadecane dichloride tetrahydrate.

PMID- 11999535
TI  - Crystal structure of 1,1,1-triphenyl-4-(10-benz[a]azulenyl)-2-butanone.

PMID- 11999536
TI  - Effect of a rapeseed oil substituting diet on serum lipids and lipoproteins in
      children and adolescents with familial hypercholesterolemia.
AB  - OBJECTIVE: Familial hypercholesterolemia (FH) is a predominantly inherited
      disorder, which contributes to a defect of the LDL-cholesterol receptor. For
      adults with familial hypercholesterolemia (FH), it is known that a supplementary
      diet of monounsaturated fatty acids reduces elevated levels of total cholesterol
      and LDL-cholesterol and may further increase HDL-cholesterol. In particular the
      reduced intake of dietary fat reduces total serum cholesterol and LDL-cholesterol
      in the range of 10% to 15% and inhibits LDL-oxidation. Once the diagnosis of
      familial hypercholesterolemia is made in early childhood a supplementary diet
      with rapeseed oil should be started as early as possible to prevent development
      of atherosclerosis and subsequent complications. So far there are no reports of a
      lipid lowering diet enriched with rapeseed oil in children and adolescents.
      METHODS: Seventeen children and young adolescents (male = 6, female = 11, ages 4
      to 19 years) diagnosed with FH were enrolled in this study. They received dietary
      training and a classical low fat/low cholesterol diet enriched with rapeseed oil
      over five months. In the first two months they received orally mean 15 g/day (8
      23 g/day), for the remaining three months mean 22 g/day (15-30 g/day) rapeseed
      oil. The calculation of the three-days dietary protocols showed the following
      characteristics: 29.5% calories from fat, 14.3% calories from protein and 54.6%
      calories from carbohydrates. The subjects had six sessions of dietary counseling,
      and serum lipids levels and lipoprotein(a) were estimated; each month's diet
      adherence was controlled by a dietitian and discussed with the patients and their
      families during this five-month study. RESULTS: During five months of rapeseed
      oil diet serum triglycerides decreased by 29% (119.2+/-62.8 mg/dL vs. 84.9 mean
      +/- 39.7 mg/dL), VLDL-cholesterol by 27% (23+/-12 mg/dL vs. 17+/-8 mg/dL), total
      cholesterol by 10% (233+/-35 mg/dL vs. 213+/-36 mg/dL), LDL-cholesterol by 7%
      (151+/-31 mg/dL vs. 142+/-31 mg/dL). HDL-cholesterol (59+/-15 mg/dL vs. 57+/-11
      mg/dL) and Lp(a) (29.8+/-36.3 mg/dL vs. 32.6+/-40.7 mg/dL) were not changed
      significantly. The diet was well accepted; in most families a sustained change
      was reported. CONCLUSIONS: Our results indicate that in children and adolescents
      with FH a lipid-lowering diet with rapeseed oil has a similar effect on total
      serum cholesterol and LDL-cholesterol compared to classical cholesterol reduction
      diets (step I). However, an additional pronounced effect on lowering of
      triglycerides and VLDL-cholesterol can be observed.

PMID- 11999537
TI  - Vitamin B12 and folic acid in children with intestinal parasitic infection.
AB  - OBJECTIVE: To determine prospectively plasma levels of vitamin B12 and folic acid
      in children with intestinal parasitic infection before and three months after
      antiparasitic treatment. METHODS: 3036 stool samples were collected from 1959
      children and 939 cello-tape anal swabs were taken from 688 children for
      intestinal parasite investigation. Of these, 155 children were identified as
      having a parasitic infection; however, only 86 were followed up during this
      study: 26 children with Giardia lamblia infection were treated with tinidazole
      and metronidazole, pyrantel pamoate was used in the treatment of 40 children with
      Enterobius vermicularis, and 20 patients infected with Cryptosporidium parvum
      received only symptomatic treatment. Vitamin B12 and folic acid levels were
      measured by radioimmunoassay, before and three months after the completion of
      treatment. RESULTS: Vitamin B12 serum concentrations did not show any significant
      differences among the three groups. There was a significant increase in vitamin
      B12 serum concentrations after three months of anti-parasitic treatment (630.57+/
      200.97 vs. 667.97+/-181.55 pg/dL, p = 0.002, n = 86). Paired analysis in each
      group showed only significant increases for vitamin B12 in the Giardia lamblia
      group and in the Enterobius vermicularis group. No statistically significant
      differences were found for folic acid serum concentrations before and three
      months after treatment. CONCLUSIONS: Patients with symptomatic infection by
      Giardia lamblia and Enterobius vermicularis have lower vitamin B12 levels than
      asymptomatic patients. This could reflect a more affected intestinal mucous.
      These results could present the opportunity to treat these parasitic infections
      and to use vitamin B12 supplementation in symptomatic children with Giardia
      lamblia and Enterobius vermicularis infection.

PMID- 11999538
TI  - Contribution of meals and snacks to nutrient intake of male and female elite
      figure skaters during peak competitive season.
AB  - OBJECTIVE: To examine the contribution of breakfast, lunch, dinner and snack to
      the macronutrient and micronutrient intake of elite male and female figure
      skaters during their competitive season. SUBJECTS: Male (n = 46) and female (n =
      48) figure skaters who participated in the 1999 U.S. National Figure Skating
      Championships completed the study. METHODS: Each athlete completed three-day food
      records, during the athlete's competitive season. Food records were analyzed
      using Nutritionist V software. Macronutrient and micronutrient contributions from
      meals were assessed. RESULTS: Lunch and dinner meals were the main contributors
      to the total calorie intake of these skaters (27% and 32%, respectively).
      Likewise, lunch and dinner were the main contributors to the total protein (27%
      and 41%), carbohydrate (26% and 29%), fat (30% and 32%), saturated fat (29% and
      32%) and polyunsaturated fat (31% and 32%) intakes. Dinner was the main source of
      the monounsaturated fat (34%), cholesterol (40%) and dietary fiber (34%).
      Breakfast was the main source of dietary folate (36%), whereas iron and calcium
      intakes were mainly contributed by breakfast and dinner (29% and 32%, 27% and
      29%, respectively). CONCLUSION: These elite figure skaters appear to be starting
      their day with low energy reserves and therefore need to be educated about the
      benefits of consuming breakfast. These athletes also need to be educated about
      consuming adequate calories throughout the day in order to meet the energy needs
      of their activity. It is thus important to monitor eating patterns throughout the
      day to ensure adequate energy intake to sustain the physical and mental aspects
      of the athletes' training and performance.

PMID- 11999539
TI  - The effect of high- and low-glycemic index energy restricted diets on plasma
      lipid and glucose profiles in type 2 diabetic subjects with varying glycemic
      control.
AB  - OBJECTIVE: To determine whether glycemic index (GI) differentially affects
      improved glucose and lipid profiles observed during weight loss in overweight
      subjects previously diagnosed with type 2 diabetes with variable glucose
      tolerance. METHODS: Twenty-three female and twenty-two male overweight subjects
      participated in 12 weeks of energy restriction (average BMI 33.2 kg/m2, age 56.7
      years, glycated hemoglobin (GHb) 6.7%). After a four-week run-in on a high
      saturated fat (SFA) diet (1540 kcal/day, 17% SFA), the free-living subjects were
      randomly assigned to either a high- (75 GI units) or low- (43 GI units) GI diet
      (1440 kcal/day, 60% carbohydrate, 5% SFA) for eight weeks. Weight, serum lipids,
      plasma glucose and glycated hemoglobin were measured every four weeks. An oral
      glucose tolerance test (OGTT) was also performed at baseline, weeks 4 and 12.
      From the baseline OGTT results subjects were divided into three groups of low,
      median and high glucose tolerance. RESULTS: At baseline, BMI, age and glycated
      hemoglobin concentrations were not different between subjects allocated to the
      high- or low-GI diets. After four weeks, weight loss was 3.6+/-0.3 kg. Fasting
      glucose (-5.6%), glycated hemoglobin (-2.8%), area under the glucose curve (
      13.0%) and triglyceride (-13.8%) concentrations were reduced (p < 0.02). Between
      weeks 4 and 12 reductions were observed in weight (-4.9%), fasting glucose (
      4.6%), area under glucose curve (-10.1%), glycated hemoglobin (-7.2%),
      triglyceride (-7.5%) and LDL-C (-13.2%) concentrations. Weight loss was not
      different between low and high-GI diets. However, glycated hemoglobin was reduced
      twofold more in subjects consuming a low-GI diet as compared to subjects
      consuming a high-GI diet, but this was not statistically significant. LDL
      concentrations were also reduced more in subjects with low glucose tolerance on
      the low-GI diet (p = 0.02). CONCLUSION: Weight loss produces substantial
      improvements in glycemic control and lipoprotein metabolism. Lowering the
      glycemic index of high carbohydrate, low fat diets increases the fall in LDL
      cholesterol in subjects with type 2 diabetes with low glucose tolerance, but has
      little effect on glycemic control.

PMID- 11999540
TI  - New frontiers in weight management.

PMID- 11999541
TI  - Obesity and health risks.
AB  - Childhood obesity is multi-factorial in etiology. Several factors contribute to
      the etiology of childhood obesity, and childhood obesity is itself associated
      with significant morbidity. This article focuses on the health risks of childhood
      obesity and on the prenatal and childhood influences that contribute to the
      genesis of childhood obesity.

PMID- 11999542
TI  - The influence of dietary composition on energy intake and body weight.
AB  - We review evidence regarding the influence of dietary fat, fiber, the glycemic
      index and sugar on energy intake and body weight. Although data from
      comprehensive long-term studies are lacking, published investigations suggest
      that the previous focus on lowering dietary fat as a means for promoting negative
      energy balance has led to an underestimation of the potential role of dietary
      composition in promoting reductions in energy intake and weight loss. More
      randomized clinical trials are needed to examine the relative utility of
      different putative dietary factors in the treatment of obesity.

PMID- 11999543
TI  - Regulation of adiposity and obesity risk by dietary calcium: mechanisms and
      implications.
AB  - Dietary calcium plays a pivotal role in the regulation of energy metabolism; high
      calcium diets attenuate adipocyte lipid accretion and weight gain during periods
      of overconsumption of an energy-dense diet and increase lipolysis and preserve
      thermogenesis during caloric restriction, thereby markedly accelerating weight
      loss. Intracellular Ca2+ has a key role in regulating adipocyte lipid metabolism
      and triglyceride storage, with increased intracellular Ca2+ resulting in
      stimulation of lipogenic gene expression and lipogenesis, suppression of
      lipolysis, and increased lipid filling and adiposity. Moreover, we have recently
      demonstrated that the increased calcitriol released in response to low calcium
      diets stimulates Ca2+ influx in human adipocytes and thereby promotes adiposity.
      Accordingly, suppressing calcitriol levels by increasing dietary calcium is an
      attractive target for the prevention and management of obesity. In support of
      this concept, transgenic mice expressing the agouti gene specifically in
      adipocytes (a human-like pattern) respond to low calcium diets with accelerated
      weight gain and fat accretion, while high calcium diets markedly inhibit
      lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat
      accretion and weight gain in animals maintained at identical caloric intakes.
      Further, low calcium diets impede body fat loss, while high calcium diets
      markedly accelerate fat loss in transgenic mice subjected to caloric restriction.
      These findings are further supported by clinical and epidemiological data
      demonstrating a profound reduction in the odds of being obese associated with
      increasing dietary calcium intake. Notably, dairy sources of calcium exert a
      significantly greater anti-obesity effect than supplemental sources in each of
      these studies, possibly due to the effects of other bioactive compounds, such as
      the angiotensin converting enzyme inhibitor found in milk, on adipocyte
      metabolism, indicating an important role for dairy products in the control of
      obesity.

PMID- 11999544
TI  - Calcium and weight: clinical studies.
AB  - Data from six observational studies and three controlled trials in which calcium
      intake was the independent variable (and either bone mass or blood pressure the
      original outcome variable) have been reanalyzed to evaluate the effect of calcium
      intake on body weight and body fat. Analysis reveals a consistent effect of
      higher calcium intakes, expressed as lower body fat and/or body weight, and
      reduced weight gain at midlife. Similarly, studies relating nutrient intake to
      body composition report negative associations between calcium intake and body
      weight at midlife and between calcium and body fat accumulation during childhood.
      There is a fairly consistent effect size, with each 300 mg increment in regular
      calcium intake associated with approximately 1 kg less body fat in children and
      2.5-3.0 kg lower body weight in adults. Taken together these data suggest that
      increasing calcium intake by the equivalent of two dairy servings per day could
      reduce the risk of overweight substantially, perhaps by as much as 70 percent.

PMID- 11999545
TI  - Reflections on the use of food policy for waging war on cancer.

PMID- 11999546
TI  - Nutrition in cancer prevention: an integrated approach.
AB  - There is considerable evidence that the war on cancer is not being won. There is,
      however, strong evidence that a substantial fraction of cancer can be prevented
      by using existing nutritional knowledge. In this paper we discuss strategies for
      reducing cancer incidence by implementing this knowledge. The most obvious route
      for persuading large numbers to change their diets is by individual counseling in
      a health-care setting, public education campaigns and interventions at the
      worksite. However, such health promotion actions have met with only limited
      success. For efforts to change population diets to be successful, a vital
      component must include changes in govemment policies. Examples of the tools that
      need to be employed are restrictions on advertising and marketing. Effective
      action will likely require an economic dimension, namely the employment of
      taxation and subsidies, for instance, by taxing unhealthy food choices and by
      subsidizing fruit and vegetables.

PMID- 11999547
TI  - Zinc deficiency in nursing infants.
AB  - Zinc deficiency during nursing can occur even in breast-fed infants. Zinc
      reserves accumulated during fetal development modulate the infant's
      susceptibility to zinc deficiency. Improvement of maternal zinc nutrition during
      pregnancy is the key for infant's zinc nutritional support and prevention of low
      for-lactation-age zinc concentrations of breast-milk.

PMID- 11999548
TI  - Feeding behaviors and other motor development in healthy children (2-24 months).
AB  - OBJECTIVES: To monitor infant's gross, fine and oral motor development patterns
      related to feeding. DESIGN: An incomplete block design was used with 57 to 60
      (sample = 98) mothers interviewed when their children were 2, 3, 4, 6, 8, 10, 12,
      16 and 24 months (within +/- 5 days of birth date). Each mother had 5 to 6
      interviews. SETTING: Selected developmental feeding behaviors were monitored
      using in-home interviews conducted by trained interviewers (n = 2). At each
      interview, mothers reported the child's age when behaviors first occurred, and
      anthropometric measurements were performed. SUBJECTS: Subjects were healthy white
      children who lived mostly in homes with educated two-parent families of upper
      socioeconomic status. RESULTS: Mean behavioral ages were within normal ranges
      reported in the literature, whereas individuals exhibited a wide diversity in
      reported ages. Examples of gross motor skills (age in months, +/- SD) included
      sitting without help (5.50+/-2.08) and crawling (8.00+/-1.55). Mean ages for self
      feeding fine motor skills showed children reaching for a spoon when hungry
      (5.47+/-1.44), using fingers to rake food toward self (8.87+/-2.58) and using
      fingers to self-feed soft foods (13.52+/-2.83). Oral behaviors included children
      opening their mouth when food approached (4.46+/-1.37), eating food with tiny
      lumps (8.70+/-2.03) and chewing and swallowing firmer foods without choking
      (12.17+/-2.28). CONCLUSIONS: Mean ages for feeding behaviors occurred within
      expected age ranges associated with normal development. However, mothers reported
      that individual children exhibited a wide age range for achieving these
      behaviors. Our results should be considered in counseling mothers about infant
      feeding practices.

PMID- 11999549
TI  - Beneficial effects of soybean isoflavone supplementation on bone metabolism and
      serum lipids in postmenopausal japanese women: a four-week study.
AB  - OBJECTIVE: The aim of this study was to determine the effects of soy isoflavones
      with weak estrogen-like activities both on bone metabolism and on serum lipids in
      perimenopausal women. METHODS: Twenty-three healthy perimenopausal women were
      assigned randomly to either isoflavone or placebo groups. The isoflavone group (n
      = 12) received daily capsules of soy isoflavone extract (61.8 mg of isoflavones)
      and the placebo group (n = 11) received daily placebo capsules for four weeks.
      Urinary excretion of isoflavone was measured at weeks 0, 2 and 4. Urinary
      excretion of pyridinoline and deoxypyridinoline, bone stiffness and levels of
      serum cholesterol, triglyceride and cholesterol fractions were measured at weeks
      0 and 4. RESULTS: As compared to the placebo group, urinary isoflavone, primarily
      daidzein, excretion was increased at weeks 2 and 4 in the isoflavone group.
      Excretion of bone resorption markers was reduced significantly in the isoflavone
      group. Both total serum cholesterol and LDL cholesterol were decreased
      significantly in the isoflavone group. Other serum biochemical parameters were
      not changed in either group. CONCLUSION: Soy isoflavone supplementation for four
      weeks showed potentially beneficial effects on bone metabolism and on serum
      lipids in perimenopausal women. These effects could have the potential to reduce
      the risks of postmenopausal osteoporosis and of cardiovascular diseases in such
      women.

PMID- 11999550
TI  - Angiogenic and lymphangiogenic molecules in hematological malignancies.
AB  - In this review, the role of angiogenic and lymphangiogenic growth factors in
      hematological malignancies is summarized, alongside with possible therapeutic
      applications. Recent data demonstrate the importance of angiogenesis in
      hematologic malignancies including leukemia, lymphoma, and multiple myeloma.
      Expression of angiogenic polypeptides vascular endothelial growth factor (VEGF)
      and basic fibroblast growth factor (bFGF) associate with clinical characteristics
      in human leukemia and lymphoma, and their serum concentrations serve as
      predictors of poor prognosis. VEGF and VEGF-C also act as survival factors on
      leukemia. Furthermore, certain hematological malignancies both produce angiogenic
      or lymphangiogenic growth factors including VEGF and VEGF-C, and also express
      their receptors, resulting in the generation of autocrine loops that may support
      cancer cell survival and proliferation. Inhibition of the action of key
      regulators of endothelial cell growth, alone or in combination with other
      antiangiogenic drugs and/or established chemo- or immunotherapy regimens, is a
      potential target for therapeutic intervention in hematological malignancies.

PMID- 11999551
TI  - Cell cycle control genes and hematopoietic cell differentiation.
AB  - To maintain the fidelity and integrity of blood formation, the cell cycle is
      under strict regulation during hematopoietic cell differentiation. This review
      summarizes recent studies, including our own, on the expression of cell cycle
      control genes in hematopoietic stem cells and its changes during differentiation.
      In our study, mRNA expression of cyclin-dependent kinases (cdks) and cyclins,
      except cdk4, was found to be generally suppressed in CD34+ cells isolated from
      the bone marrow of healthy volunteers. Among four major cdk inhibitors, p16 was
      expressed higher in CD34+ cells than in CD34 bone marrow mononuclear cells,
      whereas the amounts of p21 and p27 transcripts increased in the CD34 population.
      The behavior of cell cycle control genes during hematopoietic differentiation was
      classified into four patterns: (i) universal up-regulation (cdc2, cdk2, cyclin A,
      cyclin B, p21); (ii) up-regulation in specific lineages (cyclin D1, cyclin D3,
      and p5); (iii) no induction or stable expression (cdk4, cyclin D2, cyclin E, and
      p27); and (iv) universal down-regulation (p16). Lineage-specific changes include
      a sustained elevation of cdc2 and cyclin A during erythroid differentiation,
      cyclin D1 and p15 induction in myeloid lineage cells, and selective up-regulation
      of cyclin D3 during megakaryocyte development. These results suggest that the
      expression of cell cycle control genes is distinctively regulated in a lineage
      dependent manner, reflecting the cell cycle characteristics of each lineage.
      Additional data from other laboratories are summarized and their significance is
      discussed in comparison with our findings.

PMID- 11999552
TI  - Neutrophil gelatinase B and chemokines in leukocytosis and stem cell
      mobilization.
AB  - Leukocytosis is a physiopathological mechanism primarily to combat infections,
      whereas stem cell mobilization is induced for therapeutical purposes. Both
      processes are dependent on the balance between leukocyte and stem cell retention
      and mobilization. The retention is mediated by the specific architecture of the
      bone marrow, adhesion molecules and the production of chemokines in the bone
      marrow, which attract escaped immature cells to the marrow. Mobilization is the
      effect of the action of "peripheral" chemokines, such as interleukin-8 (IL-8 or
      CXCL8) and the remodeling of the matrix and basement membranes by matrix enzymes,
      such as gelatinase B (MMP-9). Recent studies lead to the conclusion that
      neutrophils, IL-8/CXCL8 and gelatinase B/MMP-9 play control roles in leukocytosis
      and stem cell mobilization. Neutrophils are the predominant circulating leukocyte
      type and IL-8/CXCL8 is the major neutrophil chemoattractant in humans. Gelatinase
      B and no gelatinase A is rapidly released from prestored granules after
      activation of neutrophils by IL-8/CXCL8. Moreover, neutrophils do not produce
      TIMP-1 and can chemically activate latent progelatinase B. Activated gelatinase B
      catalyses the aminoterminal truncation of IL-8/CXCL8 into a tenfold more potent
      chemokine. This implies that, when IL-8/CXCL8 appears in the circulation, the
      bone marrow is instructed to release neutrophils and concomitantly stem cells.
      These studies suggest that IL-8/CXCL8 and gelatinase B/MMP-9 are targets for the
      modulation of stem cell mobilization.

PMID- 11999553
TI  - Dysregulation of apoptosis and a novel mechanism of defective apoptotic signal
      transduction in human B-cell neoplasms.
AB  - Apoptotic cell death is essential for normal B-cell development and for shaping
      the B-cell repertoire. Dysregulation of the Bcl-2 related proteins and
      alterations of the p53/p14ARF pathway are implicated in the pathogenesis and
      treatment resistance in human B-cell malignancies. We found a novel mechanism of
      dysregulated apoptosis in human B lymphoma Raji cells that differs from that of
      altered Bcl-2 and p53 functions. This cell line was resistant to nuclear
      apoptosis induced by various stimuli, and neither mitochondrial activation nor
      activation of caspase-3 led to DNA fragmentation. DNA in purified Raji nuclei was
      degraded in the presence of lysates from the apoptosis-sensitive cell line HL-60,
      whereas Raji cell lysates did not induce DNA fragmentation in HL-60 nuclei.
      Cleavage of ICAD/DFF-45 was normal. These results indicate that the apoptosis
      signal transduction pathway is defective downstream of caspase-3 in Raji cell
      cytoplasm. Therefore, exploring the molecular mechanism in this system should
      provide insight into apoptosis resistance in human B-cell malignancies.

PMID- 11999554
TI  - Immune complexes and apoptosis in B-cell chronic lymphocytic leukemia.
AB  - The progressive accumulation of B-cell chronic lymphocytic leukemia (B-CLL) cells
      in vivo is attributed to resistance to apoptosis, although this can be modulated
      in vitro by a variety of cellular and humoral factors (cell-cell, cell-matrix
      interactions, cytokines). We have previously reported that IgG immune complexes
      (IC) delay B-CLL cell apoptosis through a paracrine mechanism, which depends on
      monocytes and NK cells. On the other hand, despite the fact that IC effectively
      bind to type II Fc gammaRs expressed on B-CLL cells, they are unable to deliver
      transmembrane signals. We speculate that this lack of responsiveness of resting B
      CLL cells to IC could be overcome by activation. The analysis of this possibility
      would be relevant since the presence of circulating IC is a common feature in B
      CLL patients.

PMID- 11999555
TI  - Apoptosis and prognostic factors in myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are a group of disorders characterized by
      peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is
      thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in
      ineffective hematopoiesis. Several studies have confirmed the presence of a high
      apoptotic rate and proliferative state in the bone marrow of MDS. However, MDS is
      a heterogeneous disease from the point of view of prognosis. Some patients
      develop only anemia and show long survival with or without maintenance therapy,
      while others develop fatal pancytopenia or leukemic changes and therefore show a
      poor prognosis. This review focuses on the relationship between prognosis and
      apoptotic or proliferative processes affecting hematopoietic cells in the bone
      marrow of patients with MDS.

PMID- 11999556
TI  - Erythropoietin receptor in myelodysplastic syndrome and leukemia.
AB  - Erythropoietin (Epo) is one of the main regulators of growth and differentiation
      of hematopoietic cells. In normal bone marrow cells, the amount of erythropoietin
      receptor (EpoR) was highest in the CD34+ CD38- subset, and decreased on lineage
      committed progenitor cells expressing CD38 antigens. Among the erythroid cells
      expressing GpA antigens, CD34-positive fractions expressed more EpoR than CD34
      negative fractions. Although the amounts of EpoR of bone marrow cells from
      patients with refractory anemia (RA) were less than those of normal bone marrow
      cells in all phenotypes examined, there was no statistical significant
      difference. EpoR was detected on leukemia cells from 60% of acute myeloblastic
      leukemia (AML) cases and 29% of acute lymphoblastic leukemia (ALL) cases, and
      distributed widely among all FAB-subtypes. In spite of the presence of EpoR, in
      vitro proliferative response to Epo was not observed in a large proportion of
      AML. And there was no correlation between the amount of EpoR and the in vitro
      response to EPO. Patients with both EpoR expression and in vitro response to Epo
      had shorter remission duration than those without EpoR.

PMID- 11999557
TI  - Intermediate-dose cytarabine treatment delivered at moderate infusion rates for
      de novo acute myeloid leukemia-results of a phase I-II study.
AB  - Published randomized trials on different cytarabine doses for the treatment of
      acute myeloid leukemia (AML) provide evidence of a dose-response effect. However,
      high-dose cytarabine (HIDAC) regimens correlate with increased morbidity and
      toxicity related mortality. Typical HIDAC regimens deliver 6 g/m2/d in infusion
      rates of 500-3000 mg/m2/h. However, pharmacokinetic measurements indicate that
      intracellular Ara-CTP formation is saturated at lower infusion rates than used in
      HIDAC schedules, probably causing cytarabine accumulation in the plasma and
      increased toxicity. It was our objective to investigate in a prospective non
      randomized phase I-II study feasibility and efficacy of intermediate doses of
      cytarabine delivered at the presumptive saturating moderate infusion rate (mir
      IDAC), as induction therapy in order to optimize intensified treatment for acute
      myeloid leukemia. Forty previously untreated patients younger than 60 years of
      age with de novo AML received intermediate doses of cytarabine (2-4 g/m2/d) at
      moderate infusion rates (250-667 mg/m2/h) over 6 or 8 h. Cytarabine was applied
      on alternate days (day 1, 3, 5, 7) in combination with an anthracycline as
      induction and consolidation therapy. Thirty-two of the 40 patients (80%, 95%CI:64
      91%) achieved CR after induction treatment. Treatment-related mortality during
      induction chemotherapy was 2.5%. No cerebellar toxicity was observed. After two
      to four mir-IDAC courses stem cell harvesting was successful in 71% of the
      patients eligible for high-dose chemotherapy. After three years 56% (95%CI:40
      72%) of all patients are alive and 59% (95%CI:42-76%) of the patients who entered
      CR are free of leukemia. In conclusion, favorable long-term outcomes and moderate
      acute toxicities were observed in patients with de novo AML treated with IDAC
      schedules delivered at moderate infusion rates (mir-IDAC) starting as induction
      treatment. The data suggest that a randomized trial should now be undertaken to
      examine whether mir-IDAC has clinical advantages over HIDAC.

PMID- 11999558
TI  - Therapy-related acute myeloid leukemia and myelodysplasia after successful
      treatment of acute promyelocytic leukemia.
AB  - The incidence of therapy-related myelodysplasia (t-MDS) and therapy-related acute
      myeloid leukemia (t-AML). following a high-dose chemotherapy for a prior cancer,
      is progressively increasing. Here we review patients treated by conventional
      therapy for acute promyelocytic leukemia (APL) who developed a t-MDS or t-AML in
      the course of their disease. This risk appears to be low, as only 12
      unquestionable cases have been reported so far in the literature. Alkylating
      agents and etoposide are two major agents able to induce t-MDS or t-AML. However,
      some cases ask the question of the leukemic potential of other drugs, especially
      anthracyclines. The median latent period from achievement of complete remission
      (CR) of APL to diagnosis of t-MDS or t-AML was 34 (25-40) months. All patients
      presented chromosome abnormalities, mostly deletions or loss of the long arm of
      chromosome 5 and/or 7, or balanced translocations involving the 21q22 band.
      Prognosis is poor with a median of survival of 10 (7-22) months.

PMID- 11999559
TI  - The search for optimal treatment in relapsed and refractory acute myeloid
      leukemia.
AB  - Despite the significant progress in the treatment of AML during the last 5-10
      years, 20-40% of patients still do not achieve remission with standard induction
      therapy. In addition, 50-70% of patients in CR are likely to relapse. A major
      limitation of successful AML therapy is intrinsic or acquired drug resistance.
      Several pharmacological inhibitors of mechanisms inducing chemoresistance in
      leukemic cells have been investigated. New cytotoxic drugs, agents with novel
      mechanisms of action, and new treatment strategies are currently being
      investigated. The management of refractory or relapsed AML patients is reviewed
      in this study.

PMID- 11999560
TI  - Analysis of chromosome 6q deletion in EBV-associated NK cell leukaemia/lymphoma.
AB  - Deletions involving chromosome 6q have been reported in a number of human cancers
      such as ovarian and breast tumours as well as haematopoietic malignancies. It
      seems that this region might contain tumour-suppressor genes. Putative natural
      killer cell lymphomas/leukaemias (NKLL) represent a group of recently
      characterized haematolymphoid malignancies sharing an immunophenotype of CD3/Leu4
      CD3epsilon+ CD56+, a genotype of germline T-cell receptor genes, and have a
      close association with Epstein-Barr virus (EBV). Deletion at 6q21-q25 was
      demonstrated in three recently reported cases of NKLL. Here we investigated the
      possible involvement of 6q deletions in the pathogenesis, and especially the
      tumorigenesis of NKLL. The regions of D6S1574 (6p25), DS276 (6p12), D6S257
      (6q11), D6S434 (6q14), D6S287 (6q15), D6S292 (6q21), D6S308 (6q22), D6S264
      (6q25), and D6S446 (6q26) were analysed by PCR in 25 cases of NKLL, including
      seven cases with chronic NK leukaemia, six with acute NK leukaemia and 12 with NK
      lymphoma. 6q deletions, especially 6q15-25, were frequently detected, but 6p
      deletions were not detected in any cases. Analysis of 6q21 showed possible
      deletion in two of seven cases (29%) with chronic NK leukaemia, three of six
      (50%) with acute leukaemia, and 12 of 12 (100%) with NK lymphoma. The frequency
      of deletion increased in clinical phases. In three cases with lymphoma,
      fluorescence in situ hybridisation was performed, which confirmed 6q21 deletion
      in two cases, although 6q telomeric and centromeric regions were preserved. The
      other case failed to show deletion. Our results suggest that 6q deletion,
      especially 6q21-25, might be involved in NKLL tumorigenesis, and support the
      presence of the tumour suppressor genes associated with the development of NKLL.

PMID- 11999561
TI  - In vitro drug resistance profiles of adult acute lymphoblastic leukemia: possible
      explanation for difference in outcome to similar therapeutic regimens.
AB  - Age has important prognostic impact in acute lymphoblastic leukemia (ALL). Adults
      with ALL have a worse prognosis compared to children. This may be due to
      different, unfavorable biology, poor treatment tolerance, drug resistance, higher
      expression of drug resistance related proteins. The lymphoblasts from adult ALL
      show an increased in vitro resistance to cytotoxic drugs, including prednisolone,
      dexamethasone, cytosine arabinoside, daunorubicin, L-asparaginase and
      methotrexate. Glucocorticoid resistance may be a fundamental difference between
      children, adolescents and adults with ALL, which may underlie different
      biological aspects and also explain the difference in prognosis. It seems that in
      vitro resistance to prednisolone with respect to the age might be a continuous
      variable in ALL patients, except infants. The greater the age, the higher the in
      vitro resistance to prednisolone. This may be due to induction of various defense
      mechanisms, such as an activation of P-glycoprotein, which develops throughout
      the life and protect the human against xenobiotics. Among a number of various
      drug resistance mechanisms, only several weak differences between adults and
      children with ALL have been reported including higher P-glycoprotein expression,
      lower methotrexate polyglutamate accumulation and possibly more often p53 gene
      mutations in adults. Intrinsic resistance, induction of drug resistance proteins
      expression during chemotherapy and co-existence of various mechanisms are common
      phenomena in adult ALL. It seems that age itself, more than drug resistance
      profile, reflects factors which have direct effect on chemotherapy response in
      adult ALL.

PMID- 11999562
TI  - Expression of the multidrug transporter P-glycoprotein is highly correlated with
      clinical outcome in childhood acute lymphoblastic leukemia: results of a long
      term prospective study.
AB  - The improved cure rate in childhood ALL may be attributed largely to the
      effective multidrug regimens currently applied in well-designed clinical trials.
      However, in a minority of patients with ALL, chemotherapy failure remains a
      leading cause of cancer related death, most probably due to cellular drug
      resistance. The better-known mechanism of such resistance is mediated by P
      glycoprotein (P-gp). In a long term prospective study (mean time of follow-up: 65
      months) the multidrug efflux pump P-gp was examined immunocytochemically in
      leukemic cells of 102 protocol-treated children with de novo acute lymphoblastic
      leukemia (ALL) and of 37 children with relapsed ALL. Fourteen percent expressed P
      gp at initial diagnosis and 35% were P-gp positive at relapse. The patients being
      P-gp positive at initial diagnosis had a higher rate of leukemic relapse than the
      P-gp negative patients (P = 0.02). In the relapsing patients, those who were P-gp
      positive had a 2.18-fold greater risk for leukemic death than those who were P-gp
      negative. Paired analysis on diagnostic and relapsed samples from 20 patients did
      not support the hypothesis of P-gp mediated expression being a chemotherapy
      induced phenomenon. The cumulative event free survival for de novo ALL patients
      was significantly higher in the P-gp negative patient group. Multivariate
      analysis showed that P-gp expression is independent of other known risk factors.
      In conclusion we strongly advise that tests for P-gp in leukemic blasts should be
      conducted for every child with ALL, since this parameter selects a subgroup of
      patients with increased risk for leukemic relapse.

PMID- 11999563
TI  - G-CSF administered in time-sequenced setting during remission induction and
      consolidation therapy of adult acute lymphoblastic leukemia has beneficial
      influence on early recovery and possibly improves long-term outcome: a randomized
      multicenter study.
AB  - Sixty-four untreated adult acute lymphoblastic leukemia (ALL) patients were
      randomized to receive chemotherapy alone, n = 31 or chemotherapy and granulocyte
      colony stimulating factor (G-CSF), n = 33. During induction patients received G
      CSF for 5 days between four weekly Epirubicin+Vcr administrations, starting 36 h
      after each application and finishing 48 h before the next one with the intention
      to possibly generate a cell cycle dependent protection of normal hematopoietic
      progenitors and to stimulate granulopoiesis. The complete remission (CR) rate
      equaled 94% in the G-CSF group and 87% in controls. Patients who received G-CSF,
      if compared to the controls, had shorter granulocytopenia during induction and
      consolidation, displayed a lower infection rate, completed the induction
      consolidation quicker and stayed shorter in hospital during induction, p < 0.001
      0.04. Follow-up at 2 years revealed a rather higher probability of survival (59
      vs. 27%, p = 0.04) and a lower relapse rate (32 vs. 60%) in G-CSF arm than in
      controls. The beneficial influence of G-CSF administered in time-sequenced
      fashion on survival needs further confirmation.

PMID- 11999564
TI  - Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for
      refractory or relapsed indolent lymphomas.
AB  - Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic
      drugs for the treatment of relapsed or refractory indolent lymphomas. The anti
      CD20 monoclonal antibody rituximab (R) has produced an overall response rate
      (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We
      posed the question whether a combination of the above agents (BMR) could improve
      these results. This study was an open label, single center pilot study for
      patients with relapsed or refractory, CD20-positive (indolent) lymphoma or
      chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2,
      day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was
      repeated on day 36 or when the haematological parameters had recovered. The
      maximum therapy consisted of one BMR-cycle, followed by five BM courses.
      Treatment was stopped when the disease responded with PR/CR. During March 1999
      and December 2000, 20 patients received the BMR-regimen (four secondary high
      grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients
      was 67 years (range 36-82) and their performance status ranged from 0 to 3.
      Median number of previous treatment regimens was two (1-6). Of the lymphoma
      patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients
      were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven
      patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time
      to progression is 7 months (1-21) with a median observation time of 7 months (1
      21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after
      therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in
      4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen
      in 9/20 patients (45%). No major non-haematological toxicity was observed. In
      conclusion, BMR is a well tolerated, very effective outpatient regimen of
      treatment for relapsed and refractory indolent lymphoid malignancies.

PMID- 11999565
TI  - Expression of P53 and bcl-2 proteins in T-cell lymphoblastic lymphoma: prognostic
      implications.
AB  - In patients (pts) with non-Hodgkin's lymphoma (NHL) under 25 years, treatment
      with MCP-842 protocol, a short duration intense protocol, yields worse survival
      in pts with lymphoblastic lymphoma (LL) compared to other high grade lymphomas.
      In order to identify both favourable and unfavourable subgroups in pts with T
      cell LL (T-LL) with respect to relapse free survival following treatment with MCP
      842 protocol, we analysed the expression of p53 and bcl-2 proteins in 22 pts with
      T-LL treated at the Tata Memorial Hospital, Mumbai by immunohistochemistry. p53
      protein overexpression was noted in 59% cases and bcl-2 overexpression was noted
      in 29.4% cases. p53 expression correlated with a higher rate of relapse (p =
      0.03; RR 7.9). The 5-year relapse free survival (RFS) was better in p53 negative
      patients compared to positive patients (70 vs 38%) (log-rank sigma = 0.04). In
      conclusion, in this study, overexpression of p53 protein was common in patients
      with T-LL. T-LL pts negative for p53 are likely to benefit from the short intense
      protocol--MCL-842. Bcl-2 protein overexpression was not a prognostic factor in
      these patients.

PMID- 11999566
TI  - CD52 expression in mantle cell lymphoma.
AB  - Mantle cell lymphoma is one of the most difficult to treat of all the non
      Hodgkin's lymphomas. CAMPATH-1H, a humanized monoclonal antibody against the CD52
      antigen, has been used with some success in other lymphoproliferative diseases,
      especially chronic lymphocytic leukemia. This report demonstrates that tumor
      samples from patients with mantle cell lymphoma express the CD52 antigen and
      suggests that CAMPATH-1H should be studied in patients with mantle cell lymphoma.

PMID- 11999567
TI  - Serum levels of endogenous thrombopoietin and granulocyte-colony stimulating
      factor in patients with acute or lymphoma type adult T-cell leukemia during
      multicycle chemotherapy.
AB  - Recent multidrug chemotherapy for adult T-cell leukemia (ATL) showed improved
      findings, however, these protocols often induced persistent myelosuppression.
      Among 67 patients with acute and lymphoma type ATL treated between January 1996
      and December 1998, 42 patients died during this period and showed chemotherapy
      induced myelosuppression. To characterize the relation between the severity of
      myelosuppression and the endogenous thrombopoietin (TPO) or granulocyte-colony
      stimulating factor (G-CSF) levels in ATL patients, we measured these
      hematopoietic factors using ELISA method. Nineteen patients with acute or
      lymphoma type ATL and 16 healthy individuals were examined. During
      thrombocytopenia, the serum TPO levels were significantly higher than that of
      controls (P < 0.0001) and were inversely correlated with the platelet counts (r =
      -0.687 P < 0.001). Later in the chemotherapy cycle, severe persistent
      thrombocytopenia occurred and TPO levels elevated and remained at a high level
      approximating the TPO levels of exogenous TPO administration (0.3 microg/kg body
      weight). On the other hand, the serum G-CSF levels with absolute neutrophil
      counts (ANC) below 0.5 x 10(9)/L were significantly higher than controls (P =
      0.009) and inversely correlated with ANC (r = -0.382 P = 0.0034). However, G-CSF
      levels in six samples obtained after 6 h of G-CSF (100-150 microg per body)
      administration was approximately 50-fold higher than that in the neutropenic
      states. These findings suggested that G-CSF can effectively reduce the severity
      and duration of intensified chemotherapy-induced neutropenia and higher dose
      exogenous TPO (higher than 0.6 microg/kg per day) therapy may be required to
      enhance platelet recovery after intensive chemotherapy in ATL patients.

PMID- 11999568
TI  - Thalidomide in low doses is effective for the treatment of resistant or relapsed
      multiple myeloma and for plasma cell leukaemia.
AB  - Thalidomide is an effective treatment for relapsed multiple myeloma (MM), but is
      associated with a significant side effect profile at higher doses. In a recent
      study, only half of the enrolled patients were able to tolerate the maximum dose
      of 800 mg/day [Singhal, S., et al. (1999) "Antitumor activity of thalidomide in
      refractory multiple myeloma", New Engl. J. Med. 341, 1565-1571]. Moreover, the
      dose-response relationship has not been defined. We report our use of low dose
      thalidomide in a small cohort of 12 patients-eight with relapsed or refractory MM
      and four with plasma cell leukaemia (PCL). Five of the 12 (42%) patients had a
      partial response, showing a median fall in their PP/BJP of 80% (63-90%) at a
      median dose of 175 mg (100-300 mg) with negligible side effects. Three of four
      patients with PCL showed an impressive response to treatment with thalidomide as
      a single agent. No patient who failed to show any evidence of response at low
      dose (<150 mg/day) responded to higher doses. In this study, thalidomide induces
      a similar rate of response at a lower and better tolerated dose than previously
      reported and produced "best ever" responses in patients with resistant PCL.

PMID- 11999569
TI  - Spinal cord compression as a primary manifestation of aggressive malignant
      lymphomas: long-term analysis of treatments with radiotherapy, chemotherapy or
      combined therapy.
AB  - A controlled clinical trial evaluated the usefulness of three different
      therapeutic approaches in the treatment of spinal cord compression (SCC) as
      primary manifestation of malignant lymphoma with the following end-points:
      neurological function, event free survival (EFS) and overall survival (OS). Forty
      eight patients with SCC as unique manifestation (IE) of malignant lymphoma, were
      randomly assigned to receive either: radiotherapy (16 patients), chemotherapy (11
      patients) or combined therapy (radiotherapy followed by chemotherapy, 21
      patients). Although neurological recovery was similar in both groups, EFS and OS
      were better in the combined therapy arm. Actuarial curves at 10 years showed that
      EFS was 50% for patients treated with radiotherapy, 46% in the chemotherapy arm
      and 76% in the combined therapy group. Overall survival was 58, 38 and 76%,
      respectively, however because of the small number of patients, no statistical
      differences were observed. Although malignant lymphoma with SCC as primary
      manifestation could be considered as a localized disease, more patients could
      have microscopic disseminated disease. The use of combined therapy improves the
      outcome in this group of patients, and so it should be considered the treatment
      of choice.

PMID- 11999570
TI  - Fludarabine therapy in Waldenstrom's macroglobulinemia patients treated
      previously with 2-chlorodeoxyadenosine.
AB  - Six patients with Waldenstrom's macroglobulinemia (WM) resistant to previous 2
      chlorodeoxyadenosine (2-CdA) therapy were treated with fludarabine. Both initial
      and subsequent therapy was administered according to the most widely used
      protocols. The median number of 2-CdA cycles given to the patients was 3.7 (range
      2-5), while fludarabine was 1.7 (range 1-2). As a result partial remission was
      achieved in two patients and stabilization of the disease in the remaining four
      in spite of the inadequate response or progressive disease after 2-CdA therapy.
      Median monoclonal IgM concentration fell from 29.4 (range 11.6-37.1) to 16.4 g/l
      (range 3.8-29.1). At the same time hemoglobin concentration increased from median
      114 (range 89-129) to 122 g/l (range 97-133). Side effects consisted of
      neutropenia (three patients) and thrombocytopenia (two patients). Two patients
      are alive with progression of the disease noted after 12 and 21 months of
      observation. One patient died as the result of cardiac disease, two others died
      of infection 5 and 16 months after cessation of therapy in the course of disease
      progression. The remaining patient was lost to follow-up after 10 months of
      observation with continuous stabilization. Our observations suggest that in WM
      patients resistant to 2-CdA, stabilization of the disease or even remission can
      be obtained with fludarabine.

PMID- 11999571
TI  - Cladribine underdosing in hairy-cell leukemia: a cause for apparent response
      failure.
AB  - While chemotherapy overdose is often readily discovered, underdosing errors are
      seldom appreciated. We report two patients with hairy-cell leukemia who
      apparently failed to respond to cladribine administered by continuous portable
      pump infusion. It was determined that both patients received one-seventh of the
      prescribed dose, although the orders were written correctly. The errors resulted
      in the administration of 1 day's dose over 1 week. The use of 7-day portable pump
      infusion therapy for cladribine can be associated with misdosing, and is an
      occult cause of apparent failure to respond in hairy-cell leukemia.

PMID- 11999572
TI  - Antigenic open reading frames from HHV-8 are present in multiple myeloma patients
      and normal individuals at similar frequency.
AB  - It has been proposed that the absence of a humoral response to human herpes virus
      8 (HHV-8) in patients with multiple myeloma (MM) reflects strain variation or the
      mutation, or absence, of the antigenic regions of HHV-8 recognized in ELISA
      screening tests. We therefore assessed DNA sequence of three antigenic regions
      (ORF65, ORF73 and ORFK8.1) and the transforming hypervariable K1 ORF of HHV-8 in
      fresh bone marrow cells, bone marrow derived dendritic cells (DCs) and bone
      marrow stromal cells (BMSCs) from 12 patients with MM and 8 normal individuals.
      HHV-8 ORFs were detectable by nested PCR in MM patients (ORF65: 67% ORF73: 22%
      and K8.1: 58%), but were also surprisingly frequent in normal individuals (ORF65:
      37%, ORF73: 12.5% and K8.1: 62%). HHV-8 sequences were more frequently detected
      in cells from BMSC and DC culture than from fresh bone marrow in MM. In contrast
      no HHV-8 sequences were detected in BMSC from normal individuals. Sequence
      analysis of ORF65 failed to demonstrate productive mutations in any MM sample. K1
      genomic sequences were detected in 42% of MM and 37% of normals and exhibited 98%
      homology with the K1-A1 HHV-8 strain. In conclusion, our data do not support the
      presence of a K1-C3 strain of HHV-8 with ORF65 expression deficiency in MM
      patients. HHV-8 infection appears to be common in the general population when
      sensitive PCR is employed and multiple samples are analyzed.

PMID- 11999573
TI  - Induction of apoptosis by cladribine (2-CdA), gemcitabine and other
      chemotherapeutic drugs on CD34+/CD38+ and CD34+/CD38- hematopoietic progenitor
      cells: selective effects of doxorubicin and 2-CdA with protection of immature
      cells.
AB  - Due to the emerging role of high dose chemotherapy with stem cell rescue and ex
      vivo purging in hematological diseases, we examined the effect of
      chemotherapeutic drugs on the rate of apoptosis in more mature CD34+/CD38+ and
      less differentiated CD34+/CD38- stem cells. CD34+ cells were obtained by cell
      apheresis from healthy donors (n = 25) or patients (n = 25) prepared for high
      dose chemotherapy and stem cell transplantation. Cells were incubated with
      different concentrations of doxorubicin, mitoxantrone, mafosphamide, cladribine
      or gemcitabine. Apoptosis was determined after 24 and 48 h. Generally, the
      percentage of apoptotic cells was higher in the more mature CD34+/CD38+
      progenitor population than in the less differentiated CD34+/CD38- cells. By
      analysis of variance (ANOVA) significantly (p < 0.05) more apoptotic cells within
      the CD34+/CD38+ progenitors were calculated after incubation with mafosphamide,
      doxorubicine and cladribine. Mafosphamide induced the highest rate of apoptosis
      on CD34+/CD38- cells, whereas doxorubicine had nearly no effect on this immature
      population. Dose effect plots for mafosphamide and doxorubicin were steep,
      suggesting a large therapeutic index. The dose response of cladribine showed a
      flat course. Furthermore we found a selective induction of apoptosis by
      doxorubicin and cladribine on more mature CD34+/CD38+ progenitors in contrast to
      simultaneous protection of CD34+/CD38- progenitors. From these findings, in
      particular the demonstrated low stem cell toxicity, we conclude that doxorubicin
      and cladribine might be efficient alternatives in ex vivo purging of autologous
      grafts, as well as safe components in primary treatment schedules of lymphomas or
      prior to stem cell harvest with respect to stem cell toxicity.

PMID- 11999574
TI  - Expression of hBUB1 in acute myeloid leukemia.
AB  - hBUB1 gene is a component of the mitotic checkpoint that monitors proper assembly
      of the mitotic spindles and the alteration of the hBUB1 gene has been found to be
      associated with chromosomal instability in some tumor cell lines. We analyzed the
      coding region of the hBUB1 gene for mutations and its expression in 92 acute
      myeloid leukemia (AML) specimens and five hematopoietic cell lines. We also used
      Southern hybridization to analyze the genomic DNA of those cases, which had
      aberrant transcription to confirm the lesion. A thymine/cytosine polymorphism at
      8 bp upstream of the 5' splice acceptor site of exon 10 was observed in Raji cell
      line and two AML specimens without a resultant change in the expression of hBUB1.
      Reduced expression and aberrant transcription of the hBUB1 gene, which may affect
      the control of mitotic checkpoint, were detected in AML specimens by reverse
      transcription-polymerase chain reaction (RT-PCR) analysis. Our study suggests
      that the mutation of the hBUB1 gene is a rare event in AML, and further studies
      are necessary to clarify its role in leukemia.

PMID- 11999575
TI  - Mismatch repair gene expression in malignant lymphoproliferative disorders of B
      cell origin.
AB  - We investigated mismatch repair (MMR) gene expression in 31 lymphoid tissue
      specimens and bone marrow aspirates with malignant lymphoproliferative disorders
      of B-cell origin (25 cases of lymphoma and six cases of plasma cell myeloma). A
      multiplex RT-PCR assay was employed to assess the relative expression of the
      hMSH2, hMLH1 and hPMS1 genes, as compared to beta-actin, which was used as an
      internal control of gene expression. MSH2 was further evaluated at the protein
      level by immunohistochemistry. The findings were compared to those of a control
      group of lymphoid tissue specimens without evidence of malignancy (n = 6).
      Changes in MMR gene expression were observed in 10 out of 31 cases of the study
      group (32%). All three MMR gene transcripts were low in two out of six plasma
      cell myelomas, which had extensive bone marrow infiltration by neoplastic cells.
      The hMSH2 transcript was present in all cases of lymphoma, while the expression
      of hMLH1 and hPMS1 was significantly low in some large B-cell lymphomas (four and
      five out of 14 cases, respectively) and in mantle cell lymphomas of the blastoid
      type (two out of two cases). No MMR gene aberrations were found in seven cases of
      B-cell lymphocytic leukemia and two cases of mantle cell lymphoma of centrocyte
      like type. These findings demonstrate that the expression rates of the hMSH2,
      hMLH1 and hPMS1 genes differ among various types of B-cell lymphoproliferative
      disorders, and suggest that MMR gene expression may be related to the natural
      history of these neoplasms. This study identified a higher incidence of MMR gene
      aberrations in lymphoma types characterized by aggressive biologic behavior, as
      compared to neoplasms with a more indolent course.

PMID- 11999576
TI  - Production of proangiogenic cytokines during thalidomide treatment of multiple
      myeloma.
AB  - Recently a growing number of studies have suggested the efficacy of thalidomide
      (THAL) in the treatment of relapsed or resistant multiple myeloma. Some of these
      studies indicate that the thalidomide antimyeloma effect is associated with
      decreased vessel density. Here we first present our experience with THAL
      treatment and then focus on the determination of the role of proangiogenic
      cytokines during THAL therapy. Thirty relapsing or resistant multiple myeloma
      (MM) patients were treated with THAL at a median dose of 400 mg/daily. Eighteen
      responded to THAL therapy and 12 were resistant or intolerant to THAL. We
      determined the plasma level of basic fibroblast growth factor (bFGF) and vascular
      endothelial growth factor (VEGF) as the main biological parameters associated
      with tumour angiogenesis. In addition I1-6 and TNFalpha levels were also assayed.
      Assessment of peripheral blood (PB) and bone marrow (BM) cytokine levels were
      done before and during THAL treatment at weeks 4 and 8 of therapy. In the
      responder group VEGF, bFGF I1-6 and TNFalpha concentrations were significantly
      decreased after four weeks of therapy both in PB and BM. In the non-responder
      group no significant changes in bFGF and VEGF levels were observed. However, a
      significant increase in IL-6 and TNF concentrations was evident. We conclude that
      the significant decrease of VEGF, bFGF, I1-6 and TNFalpha concentrations
      reflected response to THAL therapy. Also it seems that VEGF is a better marker of
      response to treatment than bFGF.

PMID- 11999577
TI  - Cell cycle retardation in monocytoid cells induced by aminopeptidase N (CD13).
AB  - Aminopeptidase N (APN, CD13) is highly expressed on human monocytes. Activation
      of leucocyte subpopulations, such as T-cells, can induce CD13 expression.
      However, little is known about the physiological role of CD13 expression on human
      leucocytes. It was suggested that CD13, similar to other peptidases, could be
      involved in control of cell growth. The hypothesis that CD13 influences
      proliferation of monocytoid cells by retarding the velocity of the cell cycle was
      tested. It was shown that CD13 expression was modulated within the cell cycle.
      Cells entering the S-phase of cell cycle decreased their CD13 surface expression.
      Occupation of the active center of CD13 with artificial ligands such as
      monoclonal antibodies (mab) or the low molecular weight inhibitor actinonin
      induced a prolongation of cell cycle and decreased the rate of cell growth.
      Additionally, after ligation of CD13 by mab the complex of CD13 and monoclonal
      antibody was actively internalized into the cell. We suggest that CD13 could have
      important functions for the proliferation of human monocytoid cells. Here we show
      for the first time that occupation of the CD13 active center by antibodies or
      inhibitors influences the cell cycle and thereby diminishes cell growth rate.
      Occupation of the active center by antibodies or inhibitors might prevent
      cleavage or binding and internalization of still unknown natural substrate(s) and
      could evoke a deceleration of the cell cycle and reduced cell growth rate.

PMID- 11999578
TI  - A pediatric case of secondary leukemia associated with t(16;21)(q24;q22)
      exhibiting the chimeric AML1-MTG16 gene.
AB  - A chimeric gene, AML1-MTG16, showing high homology to AML1-MTG8, was recently
      identified in adult leukemic patients with the abnormal karyotype
      t(16;21)(q24;q22). We recently saw a child patient of 11 years of age who
      developed acute myelogenous leukemia with the karyotype t(16;21)(q24;q22), 11
      months after autologous peripheral blood stem-cell transplantation (PBSCT) for
      acute promyelocytic leukemia with karyotype t(15;17)(q22;q11). The reciprocal
      translocation was localized by fluorescence in situ hybridization (FISH)
      analysis, reverse transcription polymerase chain reaction (RT-PCR), and Southern
      blot analysis of bone marrow blood cells and peripheral blood cells. FISH
      analysis identified a reciprocal translocation between chromosomes 16 and 21. RT
      PCR analysis identified expression of the chimeric gene AML1-MTG16. Southern blot
      analysis revealed a breakpoint occurring at a 1.4 kb Eco RI fragment between
      exons 3 and 4 of MTG16. The breakpoint is within the same region as that of
      secondary leukemias, which has been reported previously. This case suggests the
      possibility that the region of the breakpoint of MTG16 is a characteristic of
      secondary leukemia.

PMID- 11999579
TI  - Speechless after bone marrow transplantation: a rare complication of
      parainfluenza virus related group in an adult.
AB  - Upper respiratory tract (URT) viral infections may cause severe consequences
      during myeloablative bone marrow transplantation (BMT). We present a patient with
      parainfluenza virus (PIV) infection during the course of BMT. He remained
      relatively asymptomatic during the course of cytopenia, but presented with
      complete loss of voice and severe laryngitis a few days after engraftment, which
      is not usual for adult PIV infections. Seroconversion to PIV and marked increase
      in antibody titres was demonstrated, with complete lymphoid engraftment. Our case
      illustrated that the virulence of some URT viral infections depend on host immune
      factors, and may remain latent until graft versus host responses can be mounted.

PMID- 11999580
TI  - Regression of a plasmablastic lymphoma in a patient with HIV on highly active
      antiretroviral therapy.
AB  - We describe an HIV-infected 44-year-old man who presented 1 month after
      discontinuation of HAART therapy with a large mass extending from the
      mediastinum, enclosing the heart and extending through the diaphragm to the
      epigastric region. Biopsies subsequently revealed a highly aggressive non
      Hodgkin's lymphoma (NHL) producing sheets of cells with an organoid distribution.
      The cells had abundant basophilic cytoplasm and a plasmacytic appearance.
      Although immunohistochemistry failed to show either B- or T-cell markers,
      antigens consistent with plasma cells were found. An immunoglobulin heavy chain
      clonal rearrangement was identified by PCR analysis. These studies were
      supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results
      of these tests, the patient was reinitiated on his HAART regimen. He was found on
      follow-up a month later to have complete resolution of his bulky mediastinal
      mass. He remained free of disease for 3 months with subsequent rectal and
      abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support
      was begun which resulted in another remission. Plasmablastic lymphoma is now
      reported in some studies to account for 2.6% of all HIV-related NHL. Originally
      described in 1997 in a series of 16 patients, this entity is highly associated
      with HIV infection in its later stages. Often, patients present with oral or jaw
      lesions with a rapidly progressive course. The tumors have the morphologic
      appearance of a plasmacytoid tumor with high proliferative index. Markers are
      positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV
      has not been consistently reported. Therapy with standard regimens has variable
      response. One case has been reported with a 3.5 year disease free survival. The
      regression of disease after resumption of HAART therapy alone in this patient
      suggests that HAART has an important role in the treatment of lymphoma in the HIV
      infected patient.

PMID- 11999581
TI  - Spinal cord compression of dual etiology, multiple myeloma and spinal
      tuberculosis.
AB  - Spinal cord compression as an initial manifestation of multiple myeloma is a well
      known phenomenon. We report for the first time a patient with spinal cord
      compression of dual etiology, multiple myeloma and spinal tuberculosis, treated
      successfully by local radiotherapy, chemotherapy and an antituberculous regimen.

PMID- 11999582
TI  - Coexistence of Philadelphia-positive chronic granulocytic leukemia and diffuse
      large B-cell lymphoma at initial diagnosis.
AB  - We describe the rare coexistence at the time of diagnosis of Philadelphia
      positive chronic myelogenous leukemia (Ph+ CML) and non-Hodgkin's lymphoma (NHL).
      At the time of diagnosis, cytogenetic analysis of peripheral blood and bone
      marrow cells revealed the Ph chromosome translocation in all examined metaphases.
      The lymph node biopsy showed features of diffuse large B-cell lymphoma (DLBCL).
      This case may be of interest due to: (1) the rare coexistence of Ph+ CML and NHL
      at diagnosis, (2) the fact, that in contrary with previously reported cases in
      patients with antecedent or concurrent diagnosis of CML, where precursor
      lymphoblastic lymphomas are prevalent, in our patient clinical and laboratory
      findings revealed a diffuse large B-cell lymphoma, and (3) that the present case
      is an additional one confirming the poor outcome of patients with simultaneous
      occurrence of these two clinical entities.

PMID- 11999583
TI  - Progressive multifocal leukoencephalopathy in chronic lymphocytic leukemia after
      treatment with fludarabine.
AB  - A 65-year-old man with chronic lymphocytic leukemia (CLL) diagnosed 11 years ago
      and treated with standard dose of fludarabine developed a rapidly fatal
      progressive neurological syndrome. Differential diagnoses included brain
      infiltration by CLL as opposed to progressive multifocal leukoencephalopathy
      (PML). A magnetic resonance imaging (MRI) scan showed a hyperintense T2-weighted
      signal in the left frontal region. Cerebro-spinal fluid polymerase chain reaction
      (PCR) was positive for virus JC (JCV). These findings were compatible with the
      diagnosis of PML. Fludarabine has been used to treat acute leukemias, CLL and
      follicular lymphomas. Its toxicity includes myelosuppression, immunosuppression
      and sporadic life-threatening neurotoxicity, although standard doses of it are
      considered safe. Late-onset fatal cerebral dysfunction caused by JCV after
      standard-dose fludarabine has been described previously. The widespread and
      increasing use of fludarabine makes it interesting to define the potential of
      standard doses of fludarabine for causing severe neurological side-effects such
      as PML.

PMID- 11999584
TI  - Successful allogeneic stem cell transplant after invasive pulmonary zygomycosis.
AB  - We report the successful outcome of allogeneic stem cell transplant (SCT) in a
      patient with acute lymphoblastic leukaemia (ALL) and pulmonary zygomycosis
      diagnosed prior to transplant. The lesion was surgically excised and SCT
      proceeded with antifungal therapy, granulocyte transfusions and G-CSF support
      during the period of neutropenia.

PMID- 11999585
TI  - Development of a transient monoclonal gammopathy after chemotherapy in a patient
      with biphenotypic acute leukemia.
AB  - The development of a IgGk monoclonal gammopathy after a phase of bone marrow
      aplasia following chemotherapy is described in a patient suffering from
      biphenotypic acute leukemia (BAL). Paraprotein was followed by the relapse of the
      disease and disappeared during a further chemotherapy. Paraprotein could have
      been caused by an additional chemotherapy-induced genetic mutation or by a
      dysfunction in T-B cooperation observed in the phase of reconstitution of the
      immune system after medullar aplasia.

PMID- 11999586
TI  - Acute flare-up of conjunctival graft-versus-host disease with eosinophil
      infiltration in a patient with chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGvHD) is a disabling alloimmune disease.
      Acute flare-ups of alloimmune reactions can occur even at the chronic clinical
      stage necessitating modulation of immunosuppression therapy. We studied
      conjunctival lesions of a patient with an acute flare-up in cGvHD. Along with
      severe GvHD lesions, biopsies showed eosinophils with pathological signs of
      activation. Since eosinophil recruitment and activation is observed in flare-ups
      of patients with autoimmune or inflammatory bowel diseases, we suggest that
      activated eosinophils in target organs may be a marker of evolutive lesions in
      alloimmune reactions as in other kinds of inflammatory diseases.

PMID- 11999587
TI  - Post-transplant lymphoproliferative disorders: T-cell lymphoma following cardiac
      transplant.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a frequently fatal
      complication occurring after transplant. The majority of cases are of B-cell
      origin but a smaller percentage of cases are of T-cell origin. The etiology of
      these disorders is unclear, however, EBV (Epstein-Barr virus) in the context of
      immunosuppression is thought to play a role, particularly in B-cell PTLD. We
      report a case of T-cell PTLD limited to the bone marrow occurring eight years
      post-cardiac transplantation and review the literature on T-cell PTLD after heart
      transplant.

PMID- 11999588
TI  - Acute myeloblastic leukemia achieving complete remission with amifostine alone.
AB  - Amifostine, a phosphorylated thiol-amine, is known as a cytoprotective agent
      especially for cisplatin containing chemotherapies. Apart from the cytoprotective
      role, Amifostine could also be used in the treatment of hematologic malignancies
      such as myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML), as
      a treatment option or for potentiating the effects of cytotoxic agents. We tried
      to use Amifostine in a patient with AML, which did not respond to conventional
      cytotoxic chemotherapy and aimed to publish the results. The patient was a 77
      year-old male patient, he was diagnosed as AML by peripheral blood smear and bone
      marrow aspiration. Treatment commenced with low dose cytosine arabinoside (Ara-C)
      but the therapy should have ceased due to patient intolerance. The patient
      refused further therapy and he was offered to have Amifostine treatment.
      Amifostine was administered 200 mg/m2 three times a week, with ciprofloxacin,
      pentoxifyllin and dexamethasone. Dramatic response was obtained after 8 weeks of
      administration. Blast rate was reduced from 35 to 7% in bone marrow aspiration;
      pancytopenia was restored to normal levels. This remission was maintained through
      8 more weeks. Amifostine treatment was restarted after he relapsed but this time
      he did not respond to the treatment and died of gastrointestinal bleeding on the
      8th week of treatment.

PMID- 11999589
TI  - Acute disseminated encephalomyelitis after para-influenza infection post bone
      marrow transplantation.
AB  - Acute disseminated encephalomyelitis (ADEM) is a parainfectious or
      postvaccination demyelinating condition, characterized by rapid onset of
      multifocal neurological deficits, usually occurring in childhood or adolescence.
      We report case of ADEM in an allogeneic bone marrow transplant recipient, who
      presented with rapid onset of paraplegia and widespread neurological deficits 6
      weeks after parainfluenza pneumonia. Magnetic resonance imaging (MRI) showed
      typical features of ADEM, involving the subcortical white matter, brain steam and
      spinal cord. There was a rapid and complete response to pulse high-dose
      corticosteriod and intravenous immunoglobulin. The importance of recognition and
      early treatment of this rare condition in transplantation practice is emphasized.

PMID- 11999590
TI  - Development of squamous cell carcinoma of the skin during induction chemotherapy
      for acute myeloid leukemia.

PMID- 11999591
TI  - Clinical perception of phantom limb sensation in patients with brachial plexus
      block.
AB  - BACKGROUND AND OBJECTIVE: Patients' perception of limb position during regional
      anaesthesia is frequently incorrect. The incidence and nature of this phenomenon
      has not yet been completely described. The aim of this prospective study was to
      assess phantom sensation in patients undergoing a brachial plexus block. METHODS:
      Axillary block was performed in 81 patients with the aid of a peripheral nerve
      stimulator. Immediately after the block, patients were allocated randomly to two
      groups (Group 1, n = 40; Group 2, n = 41) to have the blocked limb placed either
      on their thorax or in abduction. Fifteen minutes later, when the block was
      complete, the position of the limb was changed, without the knowledge of the
      patient, to a new position of abduction and flexion of the forearm. Patients were
      questioned about the new limb position. Fifteen minutes later, the limb was then
      transiently shown to the patient and further placed 'blindly' to another
      position. Patients were once more questioned about this new position. RESULTS:
      Correct perception was more frequently observed in both groups following the
      first interview. Thirty-two and 34 patients gave at least one erroneous response
      about their limb position when it was initially placed on the thorax or in
      abduction respectively. Transient visualization of the limb position did not
      improve the rate of correct response. CONCLUSIONS: Patients' perception of the
      position of the limb after axillary block in the majority of instances was
      probably due to persisting sensory inputs from the shoulder joint, which is not
      involved in this block. This is in contrast to supraclavicular or interscalene
      blocks. A significant number of patients experienced phantom limb sensation. They
      reported an arm position in fact related to the position of their arm before the
      axillary block.

PMID- 11999592
TI  - Randomized comparison of remifentanil-propofol with a sciatic-femoral nerve block
      for out-patient knee arthroscopy.
AB  - BACKGROUND AND OBJECTIVE: To evaluate preparation and discharge times as well as
      the anaesthesia-related costs of out-patient knee arthroscopy performed with a
      combined sciatic-femoral nerve block, or a propofol-remifentanil general
      anaesthetic. METHODS: With Ethics Committee approval and written informed
      consent, 40 healthy patients were pre-medicated with intravenous midazolam (0.05
      mg kg(-1)) and ketoprofen (50 mg). They were then randomly allocated to receive
      either a combined sciatic-femoral nerve block with 25 mL mepivacaine 2% (15 mL
      for the femoral nerve, 10 mL for the sciatic nerve) (PNB group, n = 20), or a
      general anaesthetic with a continuous intravenous infusion of remifentanil (0.1
      0.3 microgkg(-1) min(-1)) and propofol (target plasma concentration 2-4 microg
      mL(-1)) with a laryngeal mask airway (GA group, n = 20). RESULTS: The median
      (range) preparation time was 16 (10-28)min in the PNB group and 13 (8-22)min in
      the GA group (P = 0.015). Ten PNB patients were directly discharged to the day
      surgery unit after the procedure as compared with one GA patient (P = 0.003).
      Discharge from the postanaesthesia care unit (PACU) required 5 (5-20) min in the
      PNB group and 23 (7-95) min in the GA group (P = 0.001). Home discharge criteria
      were fulfilled after 277 (150-485) min in the PNB group and 170 (100-400) min in
      the GA group (P = 0.005). Costs related to the time spent in the PACU were lower
      for the PNB group (1.10 euro, range Euro 0-22 euro) compared with the GA group
      (30 euro, range 0-176 euro) (P = 0.0005). There were no differences in total
      costs: PNB group 158 euro (range 105-194 euro) versus GA group 160 euro (range
      101-238 euro) (P = 0.61). CONCLUSIONS: In patients undergoing out-patient knee
      arthroscopy, the length of stay in the PACU can be shorter after a sciatic
      femoral nerve block with a small volume of mepivacaine 2% compared with a
      propofol-remifentanil anaesthetic, and there is an increased likelihood that they
      will bypass the first phase of the postoperative recovery.

PMID- 11999593
TI  - Intraoperative fetal oxygen saturation during Caesarean section: general
      anaesthesia using sevoflurane with either 100% oxygen or 50% nitrous oxide in
      oxygen.
AB  - BACKGROUND AND OBJECTIVE: The study was designed to evaluate whether the
      administration of sevoflurane in 100% oxygen for anaesthesia during Caesarean
      section would improve fetal and neonatal oxygenation compared with the
      administration of sevoflurane with 50% nitrous oxide in oxygen. METHODS: The
      randomized, single-blind controlled study examined 24 mothers, ASA I-II, at term
      undergoing Caesarean section who were allocated to receive sevoflurane in either
      100% oxygen (n = 13) or 50% nitrous oxide in oxygen (n= 11). General anaesthesia
      was induced in both groups with thiopental 4-5 mg kg(-1) followed by
      succinylcholine 1.5 mg kg(-1) to facilitate tracheal intubation. Parturients
      received sevoflurane given either in 100% O2 or in a 50:50 nitrous oxide and
      oxygen mixture, using 0.5-1.0% progressive incremental dosing up to 1.5-2.0 MAC.
      Non-invasive fetal oxygen saturation was measured between induction to delivery,
      and umbilical artery and vein PaO2 were evaluated at birth. RESULTS:
      Intraoperative fetal oxygen saturation increased in all patients after maternal
      100% oxygen administration (P < 0.01). Maternal hyperoxygenation significantly
      increased the umbilical vein and umbilical artery PaO2 and the umbilical artery
      SaO2 at birth (P < 0.0001). CONCLUSIONS: Maternal hyperoxygenation significantly
      improves fetal as well as neonatal oxygenation.

PMID- 11999594
TI  - Shorter discharge time after regional or intravenous anaesthesia in combination
      with laryngeal mask airway compared with balanced anaesthesia with endotracheal
      intubation.
AB  - BACKGROUND AND OBJECTIVE: The efficiency of operating room times can be
      significantly improved using rapid changes between operative procedures. We
      performed a retrospective analysis using electronic anaesthesia charts that
      compared anaesthesia-related times between the three most frequently performed
      types of anaesthesia (for orthopaedic surgery) to evaluate the potential for a
      quicker turn-around between cases. METHODS: A total of 5614 anaesthetic
      procedures in trauma-related orthopaedic surgery were performed from 1997 to
      1999. All were documented with an automatic record-keeping system. Data were
      compared for intravenous anaesthesia with the laryngeal mask airway, balanced
      anaesthesia with tracheal intubation and regional anaesthesia. The primary
      outcome measure was the time needed for emergence from anaesthesia after the end
      of surgery. Statistical evaluation was performed with matched triples for all
      three types of anaesthesia (155 triples for ambulatory surgery, 249 triples for
      in-patient care). RESULTS: For ambulatory surgery, the induction time was
      significantly shorter for general anaesthesia (23.7 min for intravenous
      anaesthesia, 22.7 min for balanced anaesthesia techniques) compared with regional
      anaesthesia (27.2 min). The time from the end of the surgical procedure to
      transfer of the patient out of the operating room was shortest for regional
      anaesthesia (6.3 min) compared with intravenous anaesthesia (9.0 min) and
      balanced anaesthesia (12.5 min) techniques. Results were comparable for in
      patients: regional anaesthesia required significantly longer for its induction,
      but less time for patient discharge from the operating room. CONCLUSIONS: The use
      of a regional anaesthesia technique or one involving intravenous anaesthesia in
      combination with the laryngeal mask airway may lead to a reduction in discharge
      time compared with a balanced anaesthesia technique with endotracheal intubation.
      Thus, improved use of resources may be achieved.

PMID- 11999595
TI  - Comparison of effects of remifentanil, alfentanil and fentanyl on cardiovascular
      responses to tracheal intubation in morbidly obese patients.
AB  - BACKGROUND AND OBJECTIVE: The effects of remifentanil, alfentanil and fentanyl
      were compared on cardiovascular responses to laryngoscopy and endotracheal
      intubation in morbidly obese patients. METHODS: Eighty morbidly obese ASA I-II
      patients were included in the study. Patients were randomly divided into four
      groups to receive either 1 microgkg(-1) fentanyl (Group F), 10 microgkg(-1)
      alfentanil (A), 1 microgkg(-1) followed by an infusion of 0.5 pg kg min(-1)
      remifentanil (R) or saline (P). The patients corrected weight was used to
      calculate the drug doses. Body mass indices (range) were: 54.3 +/- 7.37 (49
      78.4), 55.67 +/- 7.44 (48.5-78.4), 53.17 +/- 5.36 (48.1-63.2), and 56.3 +/- 6.09
      (46.6-67.7) kg m(-2), in Groups F, R, A and P respectively. Systolic, diastolic
      and mean arterial pressures and heart rate were measured non-invasively at three
      time points, which were 2 min before induction, 2 min after induction and 2 min
      after endotracheal intubation. RESULTS: After induction of anaesthesia, arterial
      pressures decreased significantly in all groups, but the decrease was more
      pronounced in Groups A and R. After induction, heart rate decreased significantly
      in all groups except in Group P. After intubation, haemodynamic responses were
      similar in the remifentanil, fentanyl and alfentanil groups and were within
      normal limits. In Group P, arterial pressures and heart rates were significantly
      higher. CONCLUSIONS: Alfentanil, fentanyl and remifentanil in the doses described
      had similar effects in controlling the haemodynamic response to tracheal
      intubation in ASA I-II morbidly obese patients.

PMID- 11999596
TI  - Postoperative residual curarization with cisatracurium and rocuronium infusions.
AB  - BACKGROUND AND OBJECTIVE: Monitoring of neuromuscular blockade still often relies
      on clinical judgement. Moreover, there are substantial national differences in
      the use of agents to 'reverse' their effects. We investigated the recovery
      characteristics and incidence of postoperative residual curarization after
      cisatracurium and rocuronium infusions for long duration interventions without
      systematic antagonism. METHODS: In 30 patients undergoing major surgery, we
      measured infusion dose requirements for rocuronium and cisatracurium during
      propofol anaesthesia. Infusions were discontinued at the beginning of surgical
      closure; spontaneous recovery of neuromuscular function was awaited in both
      groups. Neostigmine (50 microg kg(-1)) was administered only when a patient
      started to wake without a train-of-four ratio (TOF) of 0.9. RESULTS: In the
      cisatracurium and rocuronium groups, four (27%) and one (7%) patients,
      respectively, had a TOF ratio > or = 0.9 at the end of surgery. The TOF ratio in
      each group at that time was 51 +/- 32% for cisatracurium and 47 +/- 31% for
      rocuronium (P = 0.78). Six patients (40%) in the cisatracurium group and seven
      (47%) in the rocuronium group required neostigmine. The TOF ratio at the time of
      reversal was 63 +/- 7% for cisatracurium and 40 +/- 19% for rocuronium (P =
      0.01). The time interval between the end of surgery and a TOF ratio of 0.9 was 10
      +/- 9 min for cisatracurium and 18 +/- 13 min for rocuronium (P = n.s.).
      CONCLUSIONS: Patients receiving a cisatracurium or rocuronium infusion have a
      high incidence of postoperative residual curarization when the block is not
      antagonized. When 'reversal' is not attempted, cisatracurium seems to be safer
      than rocuronium.

PMID- 11999597
TI  - In vitro effects of 4-chloro-3-ethylphenol in skeletal muscle preparations from
      malignant hyperthermia susceptible and normal swine.
AB  - BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and
      caffeine is the current gold standard for diagnosis of malignant hyperthermia.
      This test has a sensitivity of 99.0% but a specificity of only 93.6%. Therefore,
      an alternative drug is desirable which distinguishes between malignant
      hyperthermia-susceptible and malignant hyperthermia-normal subjects with a higher
      specificity and sensitivity. METHODS: 4-chloro-3-ethylphenol has recently been
      shown to trigger Ca2+-induced Ca2+-release in skeletal muscle terminal cisternae
      and to increase the myoplasmic free Ca2+ concentration in skeletal muscle fibres.
      The purpose of this study was to investigate the ability of 4-chloro-3
      ethylphenol to distinguish between malignant hyperthermia-susceptible and
      malignant hyperthermia-normal porcine muscle specimen in the in vitro contracture
      test. Ten malignant hyperthermia-susceptible and 14 malignant hyperthermia-normal
      swine were anaesthetized and muscle biopsies were taken. For the in vitro
      contracture test muscle specimens were exposed to cumulative concentrations of 4
      chloro-3-ethylphenol (12.5 to 200 micromol L(-1)). RESULTS: 4-chloro-3
      ethylphenol produced contractures in a concentration-dependent manner in the
      malignant hyperthermia-susceptible muscle bundles. In contrast, cumulative 4
      chloro-3-ethylphenol did not generate contractures in malignant hyperthermia
      normal specimens. Contractures were significantly greater (P < 0.05) in the
      malignant hyperthermia-susceptible compared to the malignant hyperthermia-normal
      preparations in all 4-chloro-3-ethylphenol concentration steps from 50 micromol
      L(-1) to 200 micromol L(-1). There was no overlap between the two groups above a
      concentration of 75 micromol L(-1) in cumulative 4-chloro-3-ethylphenol in vitro
      contracture tests. CONCLUSIONS: It remains to be verified whether an in vitro
      contracture test with 4-chloro-3-ethylphenol can also discriminate between
      malignant hyperthermia-susceptible and malignant hyperthermia-normal humans.
      Since no prior tested agent revealed a clear differentiation in contracture
      development without overlap, the 4-chloro-3-ethylphenol test might be a promising
      new approach to the diagnosis of malignant hyperthermia.

PMID- 11999598
TI  - Lung image changes during bronchopulmonary lavage estimated using
      transoesophageal echocardiography.
AB  - Pulmonary alveolar proteinosis is often treated with bronchopulmonary lavage.
      Transoesophageal echocardiography has been used to detect lung atelectasis in
      critical situations. A 68-yr-old male with pulmonary alveolar proteinosis
      underwent bronchopulmonary lavage and was examined using transoesophageal
      echocardiography. His dependent left-lung area was observed through the
      descending aorta. Following saline infusion, no bright areas containing air were
      observed. The average area of the air-free region following instillation was 37.4
      +/- 1.8 cm2, which decreased to 22.8 +/- 2.6 cm2 after drainage (P < 0.001).
      There was a significant relationship between the percentage venous admixture and
      air-free area during lavage (P < 0.05, r = -0.76). The image of the right lung
      was unclear. Transoesophageal echocardiography can yield useful information about
      the lung during bronchopulmonary lavage.

PMID- 11999599
TI  - Peroperative opening of a patent foramen ovale caused by pulmonary artery
      obstruction due to knotted pulmonary artery catheter.

PMID- 11999600
TI  - Localized abdominal pain following sympathetic blockade with bretylium for the
      management of complex regional pain syndrome.

PMID- 11999601
TI  - Ultrasound-guided placement of intra-aortic balloon pump.

PMID- 11999602
TI  - General anaesthesia for emergency surgery during acute organophosphate poisoning.

PMID- 11999603
TI  - Postoperative hypoxaemia in a patient with patent foramen ovale.

PMID- 11999605
TI  - An unusual case of breathing circuit obstruction.

PMID- 11999604
TI  - Epidural anaesthesia in a patient with POEMS syndrome.

PMID- 11999606
TI  - Oasis or mirage? The safety of outpatient dental anaesthesia in hospital.

PMID- 11999607
TI  - Inhalation anaesthesia is cost-effective for ambulatory surgery: a clinical
      comparison with propofol during elective knee arthroscopy.
AB  - BACKGROUND AND OBJECTIVE: Cost consciousness has become increasingly important in
      anaesthesia as elsewhere in healthcare. Cost-minimization with uncompromised
      patient safety and quality requires systematic comparisons of alternative
      techniques. Inhalation anaesthesia with desflurane or sevoflurane is compared in
      this study with propofol delivered by the target controlled infusion technique.
      Directly measured drug consumption and costs and emergence times are compared.
      METHODS: Consumed anaesthetics were measured during elective arthroscopy of the
      knee, and costs were calculated for ASA I-II patients (n = 102) randomized to 3
      groups: one group received anaesthesia using propofol administered by target
      controlled infusion, the others inhalation anaesthesia with either desflurane or
      sevoflurane in combination with nitrous oxide. A partial rebreathing system was
      used with a laryngeal mask airway. Vaporizers were weighed before and after each
      anaesthetic. RESULTS: Anaesthetic duration, postoperative pain and emesis as well
      as discharge time did not differ between groups. Inhaled anaesthetic techniques
      with desflurane or sevoflurane were associated with 2-3 min shorter emergence
      times (P < 0.001) and approximately 45% lower cost for consumed anaesthetics as
      compared with a propofol technique based on target controlled infusion. The
      inclusion of waste costs improved the cost reduction to 55%. CONCLUSIONS: For
      this patient group, use of inhalation anaesthesia reduced drug costs by half and
      shortened emergence times compared to target controlled infusion with propofol
      with equal perioperative patient conditions.

PMID- 11999608
TI  - Anaesthetic management and outcome in right-lobe living liver-donor surgery.
AB  - BACKGROUND AND OBJECTIVE: We reviewed retrospectively the anaesthetic management
      and perioperative course of eight right hepatectomies for living liver donation.
      METHODS: After preoperative psychiatric evaluation, eight ASA I-II individuals
      donated the right lobe of their liver to a family member. A graft-recipient body
      weight ratio of 0.8-1.0% was required for patient selection. Indications for
      liver transplantation were: hepatitis C viral-related cirrhosis in six patients;
      combined hepatitis C and B viral cirrhosis in one patient; multifocal
      hepatocellular carcinoma--four lesions, involving both liver lobes--of hepatitis
      C viral-related cirrhosis in another patient. Indication for adult-to-adult
      living-donor liver transplantation was retained in the latter because of rapid
      deterioration of liver disease, rare recipient's blood group and extended,
      unresectable hepatocellular carcinoma. Hepatitis C viral-related cirrhosis was
      casually the primary indication for adult-to-adult living-donor liver
      transplantation in this group. The condition of the donated hepatic lobe was
      optimized by appropriate drug and perfusion management. Preoperative
      investigations included: blood tests (full cell count and film, thyroid function
      tests, pregnancy tests, full virological tests and bacteriological cultures, and
      immunological typing), chest radiograph, electrocardiogram plus Doppler cardiac
      ultrasound, spirometry, aminopyrine breath test, liver Doppler examination,
      magnetic resonance imaging, angiography and cholangiography and a volumetric
      study of the whole liver and the right lobe. Haemoglobin and lactate
      concentrations, liver function tests and international normalized ratio were
      measured before and after operation. The volume and weight of the resected right
      lobe was calculated. Anaesthesia was induced with propofol 300 mL h(-1) and
      sufentanil 0.3 microg kg(-1) intravenously; cisatracurium, 0.15 mg kg(-1), was
      given to facilitate tracheal intubation. Anaesthesia was maintained during
      normocapnic ventilation of the lungs with oxygen 40% in air, isoflurane 1-1.5 MAC
      and sufentanil. Routine anaesthetic monitoring included electrocardiography,
      pulse oximetry, invasive blood pressure, central venous pressure, urine output,
      state of neuromuscular blockade and core temperature. Periods of hypotension
      (<80% of the preoperative blood pressure) or haemodynamic instability (requiring
      inotropic or vasoactive support) were registered. Total blood loss and
      transfusion (homologous, autologous or cell-saver blood) requirements were
      measured; volume replacements were derived. RESULTS: Data are presented as mean
      (range). There was no morbidity or mortality and no periods of intraoperative
      hypotension or haemodynamic instability. The operation time averaged 619 (525
      780)min. Four donors were extubated in the operating room immediately after
      surgery; the others were extubated in the intensive care unit, where the mean
      extubation time was 16.3 (5-25)h after arrival. The estimated blood loss was 967
      (550-1,600)mL. No homologous blood was administered; five donors received
      autologous blood, intraoperatively; three donors received a cell-saver blood
      transfusion. Intraoperative fluid replacement was with crystalloids, colloids and
      4% albumin. Total urine output was 1,472 (700-3100)mL. Although intraoperative
      hypothermia occurred all subjects were normothermic at the end of operation. The
      pre- and immediately postoperative haemoglobin concentration averaged 13.6 (9.8
      15.6) and 10.5 (6.9-13.0)gdL(-1), respectively. On the first postoperative day,
      the haemoglobin was 11.7 (8.4-15.1)gdL(-1). The donors' liver function tests were
      transiently elevated in the initial postoperative period. The intensive care unit
      discharge time was 2 (1-3) days. The hospital stay was 13 (7-17) days. There was
      no morbidity or mortality. CONCLUSIONS: The study demonstrates that right-lobe
      living-donor surgery was well tolerated, without intraoperative hypotension or
      haemodynamic instability, without perioperative anaesthetic or surgical
      complications, and with an excellent general outcome.

PMID- 11999609
TI  - Effects of clonidine and dopamine on gastric tone.
AB  - BACKGROUND AND OBJECTIVE: The effects of clonidine and dopamine, both alone and
      together, on gastric tone were studied using an electronic barostat. This enabled
      volume changes to be measured in an intragastric bag with a constant preset
      pressure. METHODS: Nine healthy male volunteers were each studied on two
      occasions in a randomized order. During each study period, a continuous infusion
      of dopamine was given, starting with a dose of 2.5 microg kg(-1) min(-1), and
      then increasing at 15-min intervals to 5.0 and 7.5 microg kg(-1) min(-1).
      Clonidine 150 microg intravenously was given on one occasion during the infusion
      of dopamine (7.5 microgkg(-1) min(-1)) and on the other occasion 15 min before
      the dopamine infusion started. RESULTS: During dopamine infusion, the
      intragastric bag volume increased (gastric tone therefore decreasing) in a dose
      related manner (total increase 290 +/- 114 mL). Clonidine given either during or
      before dopamine infusion did not influence the bag volume. When the dopamine
      infusion started 15 min after clonidine, the bag volume did not change until the
      infusion of dopamine reached 7.5 microg kg(-1) min(-1) (total increase 205 +/-
      156 mL). CONCLUSIONS: Dopamine reduced gastric tone in a dose-related manner, and
      clonidine did not influence gastric tone per se. If clonidine is given before
      dopamine, the effects of dopamine are reduced.

PMID- 11999610
TI  - Thermal formation of PBDD/F from tetrabromobisphenol A--a comparison of polymer
      linked TBBP A with its additive incorporation in thermoplastics.
AB  - For a long period, polybrominated flame retardants are under discussion because
      of the formation of polybrominated dibenzo-p-dioxins (PBDD)/dibenzofurans (PBDF)
      (PBDD/F) in case of thermal stress. Concerning polymer linked tetrabromobisphenol
      A (TBBP A), formation of PBDD/F was commonly presumed to be sterically hindered
      because of the covalent fixation into the polymer backbone. Combustion
      experiments with additively incorporated TBBP A compared with its polymer linkage
      revealed, that this assumption is incorrect and has to be revised. Under same
      conditions, similar PBDD/F concentrations in the range of 17.5-19.6 mg PBBD/F per
      kg TBBP A applied were analyzed. PBDD/F homologue distribution patterns were
      almost identical predominated by low brominated PBDF. These findings for PBDD/F
      formation have to be considered in future discussions regarding thermal stress
      caused by combustion or recycling processes, including other flame retardants
      bound in polymer matrix, e.g. polybrominated polystyrene (PS), or those with
      molecular structures showing less analogy to PBDD/F, like hexabromocyclododecane.
      The second aspect introduced, is the influence of different plastics on the
      formation rates of PBDD/F. In this context, combustion experiments were performed
      in an atmosphere consisting of synthetic air and HBr. PBDD/F concentrations were
      8.47 mg/kg polyethylene, 1.67 mg/kg PS, 3.92 mg/kg phenolic resin and 18.1 mg/kg
      epoxy resin. Distribution patterns of PBDD/F homologues could partly be
      correlated with the occurrence of the precursors polybrominated benzenes and
      phenols.

PMID- 11999611
TI  - Contamination by selected chlorinated pesticides in surface waters in Hanoi,
      Vietnam.
AB  - Fifteen insecticides, which were banned in Vietnam in the period from 1990 to
      1998, were chosen for the investigation of surface water samples in Hanoi and its
      surroundings. The investigation was focused on an area of approximately 30 by 20
      km. Thirty water samples, in total were analysed: 11 samples from the Red river,
      seven from the Duong river, four from various lakes (West lake, Thuyen Quang, Bay
      Mau, Ba Mau), six from irrigation canals and two samples from wells. The
      procedure was repeated in November 1998 and in August 1999. The results showed
      that the contamination of the banned pesticides was highest in the rivers and
      then in the irrigation canals, followed by the lakes and wells. These pesticides
      could hardly be determined in just two drinking water samples (wells) and their
      concentrations rarely exceeded detection limits (0.05-0.25 ng l(-1)). The mean
      concentrations of sigmaHCHs (alpha, beta, gamma, delta-HCH) and sigmaDDTs (2,4'-,
      4,4'-DDE; 2,4'-, 4,4'-DDD; 2,4'-, 4,4'-DDT) in the rivers were 17.2 +/- 71.8 and
      43.7 +/- 79.9 ng l(-1) in the dry season (DS, November 1998), 29.3 +/- 117 and
      56.1 +/- 65.6 ng l(-1) in the rainy season (RS, August 1999), respectively.
      However, the highest concentration of DDTs detected in a river sample (DS): 0.324
      microg l(-1) was much lower than their allowable limit of concentration in
      surface waters, which is accorded with Criteria of Vietnam (1995) (DDTs < 10
      microg l(-1)). Moreover, endrin, heptachlor, aldrin were also detected in most of
      water samples with considerable mean concentrations in rivers: 25.3 +/- 40.5,
      17.4 +/- 23.8, 11.0 +/- 9.02 ng l(-1) in the DS and 18.5 +/- 23.2, 19.3 +/- 29.0,
      12.8 +/- 8.44 ng l(-1) in the RS, respectively. Heptachlor epoxide (isomer A) and
      dieldrin were detected in some water samples with lowest concentrations.

PMID- 11999612
TI  - Investigation of the soil radon variation during the winter months in Sapporo,
      Japan.
AB  - Soil radon was measured from late October 2000 to January 2001 at three test
      sites on the campus of Hokkaido University in Sapporo, Japan. Factors affecting
      radon concentrations were investigated with relation to meteorological data, as
      well as soil 226Ra content, mineral composition, water content, and pH, Eh and
      conductivity. Soil radon varied with time and with sampling site appreciably, in
      a manner unaltered by the surface geology. However, the ratio of radon isotopes
      (220Rn/222Rn) in the soil was constant within each sampling site, regardless of
      varying concentration of these nuclides during the monitoring period. Snow
      covering on the soil surfaces may affect the 222Rn concentration.

PMID- 11999613
TI  - Multivariate physicochemical characterisation and quantitative structure-property
      relationship modelling of polybrominated diphenyl ethers.
AB  - Levels of polybrominated diphenyl ethers (PBDEs) are increasing in the
      environment and may cause long-term environmental problems. Developing a model
      describing the chemical variation among the 209 possible congeners would be a
      useful step in any systematic approach for assessing the fate and risk posed by
      the PBDEs. Therefore, 40 physicochemical descriptors were derived for all PBDEs
      using a semi-empirical method (AM1), molecular mechanics, and empirically
      estimated parameters. Descriptors included heats of formation, frontier molecular
      orbital energies, atomic charges, dipole moments, logP values, and molecular
      surface areas. Principal component analysis (PCA) was used to evaluate the
      descriptors. The first four PCs, explaining 76% of the variation in the data,
      described the size, charge distribution and symmetric elements of the congeners.
      A quantitative structure-activity relationship model was constructed based on
      data for dioxin-like activity (using the luciferase bioassay) for 17 PBDEs with
      the partial least squares method. In addition, quantitative structure-property
      relationship models for gas chromatographic relative retention times on four
      capillary columns were developed. These models proved suitable to assist in the
      identification of untested PBDEs. Based on the results of the PCA, a factorial
      design was applied for selecting 21 representative congeners. PBDEs 11, 13, 17,
      32, 35, 47, 53, 77, 85, 99, 119, 135, 153, 155, 156, 169, 176, 181, 190, 192, and
      209. The spacing of these congeners in the physicochemical domain maximises the
      coverage of key factors such as molecular size and substitution pattern.
      Consideration of the selected congeners should be useful for guiding the
      synthesis of new compounds for use in future studies of the fate and biological
      effects of PBDEs.

PMID- 11999614
TI  - A laser flash photolysis study of the decay of SO4- and Cl2- radical anions in
      the presence of Cl- in aqueous solutions.
AB  - The rate constant for the reaction of sulphate radical (SO4-) with Cl- has been
      determined using laser photolysis, at 248 nm, of peroxodisulphate anions to
      produce the radicals and time resolved optical absorption of the transient
      species (at 450 or 480 nm for SO4- and 350 nm for Cl2-) for the kinetic
      determinations. The experiments were performed, in the absence of added sulphate,
      as a function of temperature and ionic strength and yielded (at an ionic strength
      of 0.0157 M): kIV = (9.90+/-0.16) x 10(9) exp((-7.12+/-2.0) kJ mol(-1)/RT) M(-1)
      s(-1), where the errors reflect the 2sigma statistical error. This reaction
      produces Cl2-, the formation and decay of which were also monitored allowing a
      determination of the rate constant of its second-order self-recombination
      reaction which gave k = (6.50+/-1.40) x 10(8) M(-1) s(-1) at 293 K and zero ionic
      strength.

PMID- 11999615
TI  - Measuring acid volatile sulphide in floodplain lake sediments: effect of reaction
      time, sample size and aeration.
AB  - For the routine measurement of acid volatile sulphide (AVS) in floodplain lake
      sediments, an earlier published diffusion method was adapted and optimised. We
      evaluated the effect of reaction time, sample weight and passive sample aeration
      on AVS recovery, and determined the method's reproducibility. The optimal
      reaction time was 4 h. Losses of AVS due to sample aeration did not occur within
      15 min of sample-air contact. Relative standard deviation was <2.5% for known
      sulphide solutions, was between 10% and 15% for AVS concentrations in sediments
      and <12% for SEM concentrations in sediments, generally. Sediment samples with
      known SEM and AVS content were used to compare results of the developed method
      with the purge-and-trap method. There is a good agreement with the purge-and-trap
      method for SEM concentrations. AVS concentrations measured with the diffusion
      method are higher than with the purge-and-trap method. We conclude that the
      adapted diffusion method is well suited for the routine measurement of AVS
      concentrations in floodplain sediments.

PMID- 11999616
TI  - Formation of involatile methylantimony species by Clostridium spp.
AB  - Trimethylantimony was detected by gas chromatography-mass spectrometry (GC-MS) in
      the headspace of a soil enrichment culture designed to promote growth of
      clostridia. Clostridial isolates from the soil enrichment culture were shown to
      biomethylate inorganic antimony in monseptic culture, using hydride generation
      gas chromatographyatomic absorption spectrometry (HG-GC-AAS). GC-MS profiles of
      headspace gases from soil enrichment cultures shown to generate
      trimethylantimony, were used to select characterised Clostridium spp for
      assessment of antimony biomethylation capability. Involatile methylantimony
      species (up to 21 microg Sb dm(-3)) were detected by HG-GC-AAS in the medium of
      monoseptic cultures of C. acetobutylicum, C. butyricum and C. cochlearium. The
      relative quantities of involatile mono-, di- and trimethylantimony species
      produced over the course of a 28-day cultivation period is consistent with
      trimethylantimony oxide being a final product of antimony biomethylation by these
      bacteria, with mono- and dimethylantimony species appearing transiently in the
      cultures as intermediates of an antimony biomethylation pathway. Clostridia may
      be the principal agents of antimony biomethylation in methanogenic environments
      and could give rise to methylated forms of antimony in both the aqueous and
      gaseous phases.

PMID- 11999617
TI  - Movement of metolachlor and terbuthylazine in core and packed soil columns.
AB  - Movement of metolachlor and terbuthylazine including a bromide tracer was studied
      in core and packed soil columns in PVC pipes (80 mm diameter, 15 mm depth) with
      two German soil types viz: silt loam and loamy silt. The breakthrough curves
      (BTCs) for bromide indicated some preferential flow of water both under
      conventional tillage (CN) and no-till (NT) simulation with silt loam soil. The
      herbicides leached to a greater extent in NT columns than in CN columns. Leaching
      was higher in loamy silt soil than in silt loam soil under CN conditions. This
      result is in agreement with the higher sorption capacity of silt loam having
      higher organic carbon compared to loamy silt having low organic carbon.
      Adsorption strength of the herbicides did not affect their breakthrough time, but
      was reflected in the slope and maximum height of the BTCs. The BTCs showed the
      expected inverse relationship between leaching and adsorption with greater
      mobility of the weakly-sorbed metolachlor than the more strongly sorbed
      terbuthylazine. Maximum amounts of the applied herbicides were recovered from the
      top soil layer in intact columns. Metolachlor was more mobile in packed columns
      than in core columns.

PMID- 11999618
TI  - Atmospheric BTX and polyaromatic hydrocarbons in Rio de Janeiro, Brazil.
AB  - Polycyclic aromatic and monoaromatic (benzene, toluene and xylene, or BTX)
      hydrocarbons were monitored in Rio de Janeiro, Brazil, during the summer of
      1998/1999. The levels of these aromatic chemicals decreased with distance from
      main roads, indicating mobile sources are the main pollutant emitters in this
      Latin American city. Benzo[ghi]perylene/indeno[1,2,3-cd]pyrene and
      benzene/toluene ratios corroborate this idea. However, higher benzene/toluene
      ratios at one of the major access routes into the city suggest pollutant inputs
      from a nearby refinery. Literature data were reviewed in order to outline
      differences and similarities among sources and levels of aromatic pollutants in
      large urban agglomerations worldwide. Concentrations of benzo[a]pyrene and
      benzene, which are well-known carcinogenic chemicals, were relatively low in Rio
      de Janeiro. This fact was attributed to specific atmospheric conditions during
      the tropical summer and differences in vehicle fuel composition.

PMID- 11999619
TI  - Organic aerosols in the Miami area, USA: temporal variability of atmospheric
      particles and wet/dry deposition.
AB  - Atmospheric particulate matter and both wet and dry deposition was collected over
      a period of nine months at one location in the metropolitan area of Miami,
      Florida. Molecular distributions and concentrations of n-alkanes, fatty acids,
      polycyclic aromatic hydrocarbons (PAHs) and hopanes were determined using weekly
      composite samples over this time period in order to determine temporal
      variability, and their possible dependence on climatic parameters such as
      temperature, rainfall and wind direction and frequency. Based on molecular
      distributions of the compounds studied, potential emission sources for the
      atmospheric particles were assessed and suggested to be mainly derived from
      automobile exhaust and natural sources. Although wet and dry deposition processes
      were observed to remove about equal amounts of organic aerosols from the Miami
      atmosphere, dry deposition was dominant in the removal of anthropogenically
      derived compounds such as PAHs and hopanes. Only very limited seasonal trends
      were observed, while wind direction and frequency was found to be the most
      important meteorological parameter controlling the temporal variability of the
      organic aerosols. This is the first detailed report of this nature for the Miami
      area.

PMID- 11999620
TI  - Heavy metal contamination in the seaweeds of the Venice lagoon.
AB  - The concentrations of heavy metals (Fe, Zn, Cu, Cd, Ni, Pb, Cr, As) were
      determined in seven seaweeds of environmental and commercial relevance (Ulva
      rigida C. Ag., Gracilaria gracilis (Stackhouse) Steentoft, L. Irvine and Farnham,
      Porphyra leucosticta Thuret, Grateloupia doryphora (Montagne) Howe., Undaria
      pinnatifida (Harv.) Suringar, Fucus virsoides J. Agardh, Cystoseira barbata
      (Good. et Wood.) Ag.) collected in four sampling sites in the lagoon of Venice,
      in spring and autumn 1999. Metals were extracted using hot concentrated acids in
      a Microwave Digestion Rotor and analysed by absorption spectrophotometry using a
      flame mode for Fe and Zn and a graphite furnace for Pb, Cr, Cd, Cu, Ni and As.
      High contamination levels, especially for Pb, were detected in Ulva and to a
      lesser extent in Gracilaria. Brown seaweeds, especially Cystoseira was highly
      contaminated by As. The least contaminated genera with all metals except As were
      Porphyra and Undaria. A concentration decrease for Zn and Cd was observed from
      the inner parts of the central lagoon, close to the industrial district, towards
      the lagoon openings to the sea.

PMID- 11999621
TI  - Triazines in the aquatic systems of the Eastern Chinese Rivers Liao-He and
      Yangtse.
AB  - The results of a one-year monitoring program on the two Eastern Chinese River
      systems, i.e. the Liao-He and the Yangtse, with special emphasis on the presence
      of triazine herbicides are presented. Sediment, suspended solids and water
      samples from both rivers were analyzed. Additionally, recovery experiments on the
      SPE-in-field-enrichment procedure and the extraction methods were performed. The
      samples were measured by gas chromatography coupled with mass spectrometry,
      electron capture detection and a newly developed mu-plasma atomic emission
      detector. A typical result of a one-year monitoring was obtained in case of the
      Liao-He: During winter, at low water period, low triazine values were found. A
      similar situation was found in early spring. Highest concentrations of atrazine
      up to 1600 ng/l were found in late spring in the water samples. Maximum
      concentrations of atrazine, simazine, propazine, simetryn and prometryn were
      observed in this season as a result of the actual use of triazines. Finally,
      after the high water period in autumn the triazine concentrations decreased.
      Additionally, atrazine adsorbed on sediment (up to 2.8 ng/g) and suspended solids
      was determined (up to 8 ng/l) during late spring sampling. Therefore, the
      logarithm of the organic carbon based sorption coefficient of atrazine could be
      calculated. Low levels of atrazine were measured in the water of Yangtse (up to
      18.3 ng/l). The concentrations from all sampling points and sampling stations of
      a particular sampling date were similar, which indicates a homogeneous
      distribution of this herbicide. Due to the high discharge rate of up to 79,000
      m3/s in case of the Yangtse a considerable mass transport of up to 57.5 kg per
      day atrazine may take place, even at concentrations below the European drinking
      water limit of 100 ng/l.

PMID- 11999622
TI  - The Hospital for Sick Children, Toronto, Longitudinal ERG study of children on
      vigabatrin.
AB  - The purpose of this longitudinal study was to identify changes in ERG responses
      associated with vigabatrin treatment. We accomplished this by recording
      longitudinally ERGs in children before and during vigabatrin treatment and
      comparing results between children on vigabatrin monotherapy and those taking
      additional anticonvulsive medications. Thirty-three children on vigabatrin
      therapy were tested; the duration between visits was approximately 6 months.
      Thirteen children were assessed initially before starting vigabatrin therapy and
      seven were assessed soon after (age range 1.5-126 months, median 6 months). The
      remaining 13 patients were already on vigabatrin at the time of initial visit
      (age range 6.5-180 months, median 16 months). ERGs were tested using the standard
      protocol established by the International Society for Clinical Electrophysiology
      of Vision, with Burian-Allen bipolar contact-lens electrodes. In addition to
      standard responses we recorded photopic oscillatory potentials (OPs). All 33
      patients were tested longitudinally on at least two occasions and 11 were tested
      on three occasions. For children whose only anticonvulsive drug was vigabatrin
      there was a significant curvature (quadratic function, p < 0.05) of the predicted
      cone b-wave amplitude with time; exhibited as increase in b-wave amplitude
      followed by subsequent decrease. Descriptive data demonstrated the same pattern
      in the group taking anticonvulsive medications in addition to vigabatrin. In most
      children the flicker amplitude declined between 6 months and 1 year of vigabatrin
      treatment. Our data demonstrated that rod responses, which may be abnormal before
      initiation of vigabatrin, did not change substantially with vigabatrin treatment.

PMID- 11999623
TI  - Visual field constriction and electrophysiological changes associated with
      vigabatrin.
AB  - PURPOSE: We investigated functional, morphological and electrophysiological
      changes in patients under anti-epileptic therapy with vigabatrin (VGB), a GABA
      aminotransferase inhibitor. METHODS: 20 epileptic patients treated with
      vigabatrin (age range 25-66 years) were enrolled in this study. The referrals
      were made by the treating neurologist, based on suspected or known visual field
      changes in these patients. Two patients had vigabatrin monotherapy, 18 patients
      were treated with vigabatrin in combination with other antiepileptic drugs. None
      of the patients reported visual complaints. Patients were examined with
      psychophysical tests including colour vision (Farnsworth D15), dark adaptation
      threshold, Goldmann visual fields and Tuebingen Automated Perimetry (90 degrees).
      A Ganzfeld ERG and an EOG following the ISCEV standard protocol were also
      obtained. Additionally, all patients were examined with the VERIS multifocal ERG
      including recordings of multifocal oscillatory potentials. RESULTS: Visual
      acuity, anterior and posterior segments, colour vision and dark adaptation
      thresholds were normal in all patients. Of 20 patients, 18 presented visual field
      constriction. All patients with visual field defects revealed altered oscillatory
      potentials waveforms in the ERG, especially in those patients with marked visual
      field defects. Multifocal oscillatory potentials were also delayed in those
      patients. In some patients a delayed cone single flash response (6/20), a reduced
      mERG amplitude (12/20) and a reduced Arden ratio (9/20) were found. CONCLUSIONS:
      The present data indicate an effect of vigabatrin on the inner retinal layers.
      Since abnormalities of the oscillatory potentials were seen in all patients with
      visual field defects a dysfunction of GABA-ergic retinal cell transmission might
      be assumed.

PMID- 11999624
TI  - Vigabatrin and retinal changes.
AB  - PURPOSE: Vigabatrin is an effective antiepileptic drug but visual field
      constriction (VFC) is found to be a severe side-effect. The aims have been to
      investigate whether visual field constriction (VFC) is related to changes in the
      electroretinography (ERG). METHODS: Twenty patients with localisations related
      epilepsy of whom one half had received vigabatrin were subjected to examination
      without informing about the treatment given. The eye examination included
      Goldmann perimetry and ERG. RESULTS: All the patients had normal visual acuity. A
      total of three patients (30%) in the vigabatrin group and none in the control
      group were found to have VFC. In the vigabatrin group ERG examination were normal
      in one case, in five cases there were changes scotopic, photopic and in the
      oscillatory potentials (OP), while the remaining four had changes in two of these
      parameters. OPs were abnormal in eight of 10 patients. Of the three patients with
      VFC all had changes in ERG. The four patients with the most severe abnormalities
      in ERG had received high daily doses of vigabatrin (4 - 6 mg) in a period. In the
      control group no abnormality was observed in five cases, and in the remaining
      five changes were present in one or two of the potentials. CONCLUSION: It is
      found that 30% of patients treated with vigabatrin, develop VFC, and none in the
      control group. Similarly more patients in the vigabatrin group had changes in the
      ERG as compared to the control group, and the number of abnormal potentials are
      significantly higher among patients with VFC compared to those without. But the
      finding of abnormal ERG results is not synonymous with VFC, and this is important
      to bear in mind when examining patients that cannot cooperate to a VF
      examination. An individual sensitivity to vigabatrin is supposed, but severe ERG
      changes occurred in all patients having had high daily doses > or = 4 g.

PMID- 11999625
TI  - Visual field and electrophysiological abnormalities due to vigabatrin.
AB  - The purpose of this study was to determine the electrophysiological changes in
      patients using the anti epileptic drug vigabatrin and to correlate these findings
      with the previously reported risk for visual field loss in these patients. In
      1998 the neurologists of both involved hospitals referred all patients on
      vigabatrin medication for ophthalmological examination to the outpatients
      clinics. Of the 33 patients whom were referred to our outpatient clinics, four
      had to be dropped from the study because of disability to perform the
      examinations the remaining 29 patients were included in the study. Standard
      ophthalmological investigations were carried out, and contrast sensitivity,
      visual field (Humphrey 30-2 and Esterman or Octopus 32), colour vision (panel
      D15), ERG and EOG according to ISCEV standards were tested. 18 patients continued
      the medication and 11 stopped taking the drug during the study. Nine of the
      patients who stopped the drug were followed during at least half a year
      afterwards, this group will be described in the combined article 'Electro
      ophthalmic recovery after withdrawal from vigabatrin' (Graniewski and Van der
      Torren, this issue). The electro-ophthalmological findings in the group of 29
      patients were correlated with the visual fields and the daily and cumulative
      dosages of vigabatrin. Of the patients, 32% showed no visual field constriction
      at all; from these patients 64% had EOG and/or ERG changes. Of the patients with
      slight to marked visual field constriction, 90% presented EOG and/or ERG changes.
      Significant correlation between daily dosages of vigabatrin and visual field
      defects was shown as well as between visual field defects and rod and cone b wave
      amplitude reductions. Cumulative vigabatrin dosages presented a significant
      correlation with EOG ratio and ERG rod b-wave amplitude. Conclusively EOG and ERG
      testing were found to be even an more accurate way to monitor the direct
      vigabatrin effect on the outer retina and is possible different from the visual
      field testing.

PMID- 11999626
TI  - Electro-ophthalmological recovery after withdrawal from vigabatrin.
AB  - This study describes the effects of stopping of the anti-epileptic drug
      vigabatrin on the visual field and electrophysiological changes in one third of
      the group of patients which is described in the paper 'Visual field and
      electrophysiological abnormalities due to vigabatrin' (Van der Torren and
      Graniewski, 2002). In 1997 several reports described the possible oculotoxic
      effect of vigabatrin followed by a reconsideration of this medication in
      epileptic patients. Vigabatrin was discontinued in one-third of the patients on
      chronic medication (mean duration 4.8 years). The visual field and
      electrophysiological examinations were repeated every 3 months if possible,
      otherwise at 6-month intervals. The EOG Arden index and the ERG rod b-wave showed
      a significant improvement when vigabatrin was discontinued. Repeated examinations
      of visual fields and electrophysiology shortly after discontinuation of the drug
      (between 1 and 3 months) and later on after 6 months and 1 year showed a recovery
      of the EOG Arden index and the ERG rod b-wave during this period. The visual
      fields did not change in either direction. CONCLUSION: the recovery effect is a
      strong argument for the hypothesis that the reduction in EOG and ERG b-wave is an
      oculotoxic effect. The electrophysiological improvement during 6 months or longer
      after discontinuation and the unchanged visual fields are an argument for the
      hypothesis that the visual field represents the irreversible intoxicating effect
      on the retina, whereas the electrophysiology represents a more direct effect on
      the retinal glial cells level.

PMID- 11999628
TI  - Vigabatrin; its effect on the electrophysiology of vision.
AB  - Vigabatrin is known to induce visual field defects in approximately one third of
      patients treated with the drug. It is apparent from electrophysiological studies
      that the cause of this defect is at retinal level probably as a result of the
      build up of GABA. Studies of electrophysiological retinal parameters such as the
      EOG and photopic, scotopic and 30-Hz flicker ERG have revealed changes in Arden
      Index, photopic a and b wave latency and amplitude, changes in oscillatory
      potentials, and changes in latency and amplitude of the 30Hz response. However,
      many of these changes such as the Arden Index, oscillatory potentials, latency
      and amplitude of photopic b wave appear to be related to current anti-epileptic
      drug treatment rather than visual field defects. Certain parameters, particularly
      the amplitude of the 30-Hz flicker response, do appear to correlate with the
      severity of the field defect. Paediatric patients treated with the drug at age 9
      years or below cannot reliably perform visual field perimetry. To identify these
      patients a special VEP H-Stimulus has been developed to produce separate
      responses from central and peripheral field stimulation by alternating at
      slightly separate rates. Forty-five healthy children between ages 3 and 10 years
      have been used to develop a normal database. This technique has a sensitivity of
      75% and a specificity of 87.5% in identifying the field defect and may be used in
      children with epilepsy from age 3 upwards.

PMID- 11999627
TI  - The effects of vigabatrin on electrophysiology and visual fields in epileptics: a
      controlled study with a discussion of possible mechanisms.
AB  - PURPOSE: To compare the visual electrophysiology and visual fields of patients
      taking vigabatrin to those of a control group of epileptics on other anti
      epileptic drugs (AEDs). METHODS: Fourteen epileptics treated with vigabatrin and
      10 control patients treated with other AEDs underwent ERG and EOG. Goldmann
      visual fields were performed and analysed using standard software to measure
      areas contained within I4e isopters. RESULTS: The cone and rod b-waves of the
      ERG, the oscillatory potential amplitudes and Arden indices were reduced in
      vigabatrin-treated subjects and the oscillatory potentials delayed. The Arden
      indices were reduced due to an increased dark trough. The areas contained within
      the I4e isopter of vigabatrin treated subjects were reduced compared to the
      control group and these areas correlated well with oscillatory potential
      amplitudes and b-wave amplitudes in the vigabatrin group only. CONCLUSIONS: The
      use of vigabatrin is associated with a reduction of the ERG cone b-wave amplitude
      and oscillatory potentials which correlates with visual field loss. The Arden
      ratio is reduced in subjects taking vigabatrin but may recover after cessation.
      However, visual loss may persist in the presence of a recovered EOG. These
      findings suggest further effects of the drug than those mediated by GABA
      receptors, and support the contention that the cause of the field loss may be at
      least in part due to retinal effects. Possible mechanisms are discussed.

PMID- 11999629
TI  - A stochastic multi-channel model for solute transport--analysis of tracer tests
      in fractured rock.
AB  - Some of the basic assumptions of the advection-dispersion model (AD-model) are
      revisited. This model assumes a continuous mixing along the flowpath similar to
      Fickian diffusion. This implies that there is a constant dispersion length
      irrespective of observation distance. This is contrary to most field
      observations. The properties of an alternative model based on the assumption that
      individual water packages can retain their identity over long distances are
      investigated. The latter model is called the multi-channel model (MCh-model).
      Inherent in the latter model is that if the waters in the different pathways are
      collected and mixed, the "dispersion length" is proportional to distance. The
      conditions for when non-mixing between adjacent streams can be assumed are
      explored. The MCh- and AD-models are found to have very similar residence time
      distributions (RTD) for Peclet numbers larger than 3. A generalized relation
      between flowrate and residence time is developed, including the so-called cubic
      law and constant aperture assumptions. The two models extrapolate very
      differently when there is strong matrix interaction. The AD-model could severely
      underestimate the effluent concentration of a tracer pulse and overestimate the
      residence time. The conditions are explored for when in-filling particles in the
      fracture will not be equilibrated but will act as if there was seemingly a much
      larger flow wetted surface (FWS). It is found that for strongly sorbing tracers,
      relatively small particles can act in this way for systems and conditions that
      are typical of many tracer tests. The assumption that the tracer residence time
      found by cautiously injecting a small stream of traced water represents the
      residence time in the whole fracture is explored. It is found that the traced
      stream can potentially sample a much larger fraction of the fracture than the
      ratio between the traced flowrate and the total pumped flowrate. The MCh-model
      was used to simulate some recent tracer tests in what is assumed to be a single
      fracture at the Aspo Hard rock laboratory in Sweden. Non-sorbing tracers, HTO and
      Uranin were used to determine the mean residence time and its variance.
      Laboratory data on diffusion and sorption properties were used to "predict" the
      RTD of the sorbing tracers. At least 30 times larger FWS or 1000 times larger
      diffusion or sorption coefficients would be needed to explain the observed BTCs.
      Some possible reasons for such behavior are also explored.

PMID- 11999630
TI  - A theoretical model of air and steam co-injection to prevent the downward
      migration of DNAPLs during steam-enhanced extraction.
AB  - When steam is injected into soil containing a dense volatile non-aqueous phase
      liquid contaminant the DNAPL vaporized within the heated soil region condenses
      and accumulates ahead of the steam condensation front. If enough DNAPL
      accumulates, gravitational forces can overcome trapping forces allowing the
      liquid contaminant to flow downward. By injecting air with steam, a portion of
      the DNAPL vapor remains suspended in equilibrium with the air, decreasing liquid
      contaminant accumulation ahead of the steam condensation front, and thus reducing
      the possibility of downward migration. In this work, a one-dimensional
      theoretical model is developed to predict the injection ratio of air to steam
      that will prevent the accumulation of volatile DNAPLs. The contaminated region is
      modeled as a one-dimensional homogeneous porous medium with an initially uniform
      distribution of a single component contaminant. Mass and energy balances are
      combined to determine the injection ratio of air to steam that eliminates
      accumulation of the contaminant ahead of the steam condensation front, and hence
      reduces the possibility of downward migration. The minimum injection ratio that
      eliminates accumulation is defined as the optimum injection ratio. Example
      calculations are presented for three DNAPLs, carbon tetrachloride (CCl4),
      trichloroethylene (TCE), and perchloroethylene (PCE). The optimum injection ratio
      of air to steam is shown to depend on the initial saturation and the volatility
      of the liquid contaminant. Numerical simulation results are presented to validate
      the model, and to illustrate downward migration for ratios less than optimum.
      Optimum injection ratios determined from numerical simulations are shown to be in
      good agreement with the theoretical model.

PMID- 11999631
TI  - Removal of NAPLs from the unsaturated zone using steam: prevention of downward
      migration by injecting mixtures of steam and air.
AB  - Steam injection for remediation of porous media contaminated by nonaqueous phase
      liquids has been shown to be a potentially efficient technology. There is,
      however, concern that the technique may lead to downward migration of separate
      phase contaminant. In this work, a modification of the steam injection technology
      is presented, where a mixture of steam and air was injected. In two-dimensional
      experiments with unsaturated porous medium contaminated with nonaqueous phase
      liquids, it was demonstrated how injection of pure steam lead to severe downward
      migration. Similar experiments, where steam and air were injected simultaneously,
      resulted in practically no downward migration and still rapid cleanup was
      achieved. The processes responsible for the prevention of downward migration when
      injecting steam-air mixtures were analyzed using a nonisothermal multiphase flow
      and transport model. Hereby, three mechanisms were identified and it was
      demonstrated how the effectiveness of these mechanisms depended on the air-to
      steam mixing ratio.

PMID- 11999632
TI  - Modeling in situ ozonation for the remediation of nonvolatile PAH-contaminated
      unsaturated soils.
AB  - Mathematical models were developed to investigate the characteristics of gaseous
      ozone transport under various soil conditions and the feasibility of in situ
      ozone venting for the remediation of unsaturated soils contaminated with
      phenanthrene. On the basis of assumptions for the mass transfer and reactions of
      ozone, three approaches were considered: equilibrium, kinetic, and lump models.
      Water-saturation-dependent reactions of gaseous ozone with soil organic matter
      (SOM) and phenanthrene were employed. The models were solved numerically by using
      the finite-difference method, and the model parameters were determined by using
      the experimental data of Hsu [The use of gaseous ozone to remediate the organic
      contaminants in the unsaturated soils, PhD Thesis, Michigan State Univ., East
      Lansing, MI, 1995]. The transport of gas-phase ozone is significantly retarded by
      ozone consumption due to reactions with SOM and phenanthrene, in addition to
      dissolution. An operation time of 156 h was required to completely remove
      phenanthrene in a 5-m natural soil column. In actual situations, however, the
      operation time is likely to be longer than the ideal time because of unknown
      factors including heterogeneity of the porous medium and the distribution of SOM
      and contaminant. The ozone transport front length was found to be very limited (<
      1 m). The sensitivity analysis indicated that SOM is the single most important
      factor affecting in situ ozonation for the remediation of unsaturated soil
      contaminated with phenanthrene. Models were found to be insensitive to the
      reaction mechanisms of phenathrene with either gas-phase ozone or dissolved
      ozone. More study is required to quantify the effect of OH* formation on the
      removal of contaminant and on ozone transport in the subsurface.

PMID- 11999633
TI  - Shallow groundwater quality on dairy farms with irrigated forage crops.
AB  - California's dairies are the largest confined animal industry in the state. A
      major portion of these dairies, which have an average herd size of nearly 1000
      animal units, are located in low-relief valleys and basins. Large amounts of
      liquid manure are generated and stored in these dairies. In the semi-arid
      climate, liquid manure is frequently applied via flood or furrow irrigation to
      forage crops that are grown almost year-round. Little is known about the impact
      of manure management practices on water quality of the extensive alluvial
      aquifers underlying these basins. The objective of this work is to assess nitrate
      and salt leaching to shallow groundwater in a relatively vulnerable hydrogeologic
      region and to quantify the impact from individual sources on dairies. The complex
      array of potential point and nonpoint sources was divided into three major source
      areas representing farm management units: (1) manure water lagoons (ponds); (2)
      feedlot or exercise yard, dry manure, and feed storage areas (corrals); and (3)
      manure irrigated forage fields (fields). An extensive shallow groundwater
      monitoring network (44 wells) was installed in five representative dairy
      operations in the northeastern San Joaquin Valley, CA. Water quality (electrical
      conductivity, nitrate-nitrogen, total Kjehldahl nitrogen) was observed over a 4
      year period. Nitrate-N, reduced nitrogen and electrical conductivity (EC,
      salinity) were subject to large spatial and temporal variability. The range of
      observed nitrate-N and salinity levels was similar on all five dairies. Average
      shallow groundwater nitrate-N concentrations within the dairies were 64 mg/l
      compared to 24 mg/l in shallow wells immediately upgradient of these dairies.
      Average EC levels were 1.9 mS/cm within the dairies and 0.8 mS/cm immediately
      upgradient. Within the dairies, nitrate-N levels did not significantly vary
      across dairy management units. However, EC levels were significantly higher in
      corral and pond areas (2.3 mS/cm) than in field areas (1.6 mS/cm) indicating
      leaching from those management units. Pond leaching was further inferred from the
      presence of reduced nitrogen in three of four wells located immediately
      downgradient of pond berms. The estimated minimum average annual groundwater
      nitrate-N and salt loading from manure-treated forage fields were 280 and 4300
      kg/ha, respectively. Leaching rates for ponds are estimated to be on the order of
      0.8 m/year, at least locally. Since manure-treated fields represent by far the
      largest land area of the dairy, proper nutrient management will be a key to
      protecting groundwater quality in dairy regions overlying alluvial aquifers.

PMID- 11999634
TI  - Recent advances in the treatment of heart failure.
AB  - Treatment strategies for patients with heart failure and left ventricular
      systolic dysfunction continue to evolve as the complex pathophysiology of this
      disease is better understood. A number of advances have been made in recent
      years, most notably the addition of beta-receptor antagonists. In addition,
      recent studies have provided important information regarding the utility of
      angiotensin receptor antagonists, aldosterone receptor antagonists, and
      natriuretic peptides in the management of heart failure. Nonpharmacologic
      advances include resynchronization therapy, which appears to confer symptomatic
      improvement in some patients, and improvements in ventricular assist device
      technology. As the importance of neurohormonal activation in the progression of
      heart failure becomes increasingly apparent, new therapeutic strategies targeting
      these neurohormonal systems are being investigated.

PMID- 11999635
TI  - Clinical significance of blood brain natriuretic peptide level measurement in the
      detection of heart disease in untreated outpatients: comparison of
      electrocardiography, chest radiography and echocardiography.
AB  - The aim of present study was to compare the predictive characteristics and cost
      benefit of measuring the concentration of blood brain natriuretic peptide (BNP),
      compared with electrocardiography (ECG), chest radiography and echocardiography,
      as a diagnostic test for heart disease. The study group comprised 130 untreated
      patients who had symptoms suggestive of heart disease. According to the results
      of additional examinations and follow-up checks, 86 patients were diagnosed as
      having heart disease and 44 patients were judged free of heart disease. Positive
      findings in each test suggestive of heart disease were checked in accordance with
      criteria, and the number of positive and negative cases for each test was
      calculated. The predictive characteristics, such as specificity, sensitivity,
      accuracy, positive and negative predictive values, of each test and the cost
      benefit value were calculated and analyzed statistically. The sensitivity,
      specificity and accuracy of blood BNP and echocardiography were significantly
      greater than those of ECG and chest radiography. Echocardiography had a
      significantly lower cost-benefit value compared with measuring blood BNP
      concentration. Thus, the blood BNP concentration had significantly higher
      predictive characteristics than ECG and chest radiography, and a cost-benefit
      value significantly greater than that of echocardiography.

PMID- 11999636
TI  - Postprandial elevation of remnant lipoprotein leads to endothelial dysfunction.
AB  - Recent studies have demonstrated that elevated levels of cholesterol in the form
      of remnant-like particles (RLP-C) induce deterioration of endothelial function
      during the fasting state, but it is not known whether postprandial RLP-C
      elevation has the same effect. The objective of this study was to assess the
      effect of postprandial RLP-C elevation on endothelial function in 24 fasting
      normolipidemic subjects. Flow-mediated dilatation (FMD) during reactive hyperemia
      in the brachial artery was investigated. Serum lipids and lipoproteins during
      fasting and 4h after regular fat-loading were measured. Subjects were divided
      into 2 groups: the high responders (postprandial RLP-C level >7.5mg/dl, n=8) and
      the normal responders (postprandial RLP-C level < or =7.5mg/dl, n=16).
      Significant increases in the level of both triglycerides and RLP-C were observed
      in the high responders. Basal FMD in the high responders (4.3+/-3.0%) was
      significantly lower than that in the normal responders (8.3+/-2.4%) (p<0.01), but
      FMD after the fat-loading in both groups did not change significantly. The change
      in RLP-C levels during the fat-loading test correlated significantly with basal
      FMD (r=-0.588, p<0.01). Multiple regression analysis showed a significant
      correlation between basal FMD and the change in RLP-C levels (r=-0.488, p<0.02).
      The results of this study suggest that postprandial RLP-C elevation could be
      associated with atherosclerotic progression even in normolipidemic subjects.

PMID- 11999637
TI  - National survey of fulminant myocarditis in Japan: therapeutic guidelines and
      long-term prognosis of using percutaneous cardiopulmonary support for fulminant
      myocarditis (special report from a scientific committee).
AB  - Although fulminant myocarditis is known as a fatal disease, patients have been
      able to recover and return to normal life with the help of mechanical
      cardiopulmonary support. However, therapeutic guidelines for using percutaneous
      cardiopulmonary support (PCPS) for fulminant myocarditis have not been
      established, and the clinical course and long-term prognosis of such patients are
      still controversial issues. The present national survey considered the current
      situation of patients as the basis for proposing therapeutic guidelines. Thirty
      of 52 patients (57.7%) survived and returned to social life. Important factors
      concerning the prognosis were the severity and grade of cardiac and renal
      dysfunction, the adjusted support flow rate to enable recovery from circulatory
      failure, and prevention of circulatory disturbances of the legs and multiple
      organ failure directly associated with PCPS. With regard to the long-term
      prognosis of patients treated with PCPS, the readmission rate was 10%, the
      exacerbation rate was 3.3%, and mortality was 10% during the average follow-up
      period of 962 days. Optimal management of the mechanical cardiopulmonary support
      and curative treatment for the myocarditis further improve the outcome of this
      disease.

PMID- 11999638
TI  - Evaluation of the quality of cardiovascular surgery care using risk
      stratification analysis according to the EuroSCORE additive model.
AB  - Risk stratification according to the EuroSCORE additive model of 803 consecutive
      patients undergoing heart and thoracic aorta surgery using cardiopulmonary bypass
      from August 1994 to December 2000 was performed. The population was divided into
      5 clinically relevant risk categories: 0-2% risk, 3-5% risk, 6-8% risk, 9-11%
      risk, and 12+% risk. Observed and predicted mortalities were compared within 3
      groups of patients divided by year of operation (early: August 1994 to September
      1996, n=260; middle: October 1996 to September 1998, n=259; late: October 1998 to
      December 2000, n=284). Overall hospital mortality was 4.5%; predicted mortality
      was 5.3% in the early, 5.1% in the middle, and 5.4% in the late period; observed
      mortality was 6.5%, 3.9%, and 3.2%, respectively (p=0.0024 in early vs late). In
      the early period, observed mortality was lower than predicted mortality in the 0
      2% and 3-5% risk categories, but higher in the other categories. Moreover,
      observed mortality increased markedly with the increase in predicted mortality.
      In the late period, observed mortality was lower than predicted mortality in all
      5 risk categories. The EuroSCORE is clinically relevant index for constructing a
      risk stratification scoring system for Japanese cardiovascular patients as well
      and shows that the quality of surgical care has improved gradually over the
      years.

PMID- 11999639
TI  - Effects of pimobendan on adverse cardiac events and physical activities in
      patients with mild to moderate chronic heart failure: the effects of pimobendan
      on chronic heart failure study (EPOCH study).
AB  - The long-term beneficial effects of pimobendan in the treatment of chronic heart
      failure (CHF) have not been established, so the present trial compared pimobendan
      (1.25 or 2.5mg twice daily) vs placebo in 306 patients with stable New York Heart
      Association class IIm or III CHF, and a radionuclide or echocardiographic left
      ventricular ejection fraction (LVEF) < or =45% despite optimal treatment with
      conventional therapy, for up to 52 weeks in a double-blind protocol. At the end
      of the 52 weeks of treatment, combined adverse cardiac events had occurred in 19
      patients in the pimobendan group (15.9%) vs 33 patients in the placebo group
      (26.3%). The cumulative incidence of combined adverse cardiac events was 45%
      lower (95% confidence interval of hazard ratio: 0.31-0.97, log-rank test:
      p=0.035) in the pimobendan group than in the placebo group. Death and
      hospitalization for cardiac causes occurred in 12 patients in the pimobendan
      group (10.1%), vs 19 patients in the placebo group (15.3%), but without
      significant difference. Treatment with pimobendan also increased the mean
      Specific Activity Scale score from 4.39+/-0.12 at baseline to 4.68+/-0.15 at 52
      weeks (p<0.05). In conclusion, long-term treatment with pimobendan significantly
      lowered morbidity and improved the physical activity of patients with mild to
      moderate CHF.

PMID- 11999640
TI  - Plasma level of homocysteine is inversely-associated with the development of
      collateral circulation in patients with single-vessel coronary artery disease.
AB  - Homocysteine induces endothelial injury and inhibits endothelial cell
      proliferation, which is a key role in angiogenesis. The purpose of this study was
      to investigate whether the plasma level of homocysteine is associated with the
      development of collaterals in patients with single-vessel coronary artery disease
      (CAD). Among a series of 105 male patients with angiographic estimation, 49 with
      single-vessel CAD were intensively investigated. Development of collaterals was
      classified by Rentrop's method. Univariate and multivariate analyses revealed
      that hyperhomocysteinemia negatively affected the development of collaterals
      (p=0.0015 and 0.0011, odds ratio 0.69, 95% confidence interval 0.52-0.90),
      whereas the duration of angina and percent stenosis evaluated by quantitative
      coronary angiography had a positive affect. Moreover, the level of homocysteine
      in the group with poorly developed collaterals (n=7, Rentrop class 0 and 1) was
      significantly higher than that in the group with well-developed collaterals
      (n=12, Rentrop class 2 and 3) of the patients with single-vessel disease showing
      total occlusion (p=0.034). This study clearly demonstrates that the plasma level
      of homocysteine is independently and inversely associated with the development of
      collateral circulation in CAD patients. Homocysteine might be a new undesirable
      aspect of ischemic heart disease through its inhibition of collateral
      development.

PMID- 11999641
TI  - Angiotensin II type 1 receptor gene adenine/cytosine1166 polymorphism is not
      associated with mitral valve prolapse syndrome in Taiwan Chinese.
AB  - The adenine/cytosine1166 (A/C1166) polymorphism of the angiotensin-II type 1
      receptor (AGTR1) gene is presumed to be associated with mitral valve prolapse
      syndrome (MVPS) in Caucasians. To investigate whether a similar association
      exists among the Chinese population in Taiwan, 100 patients with MVP diagnosed by
      echocardiography and 100 normal subjects were studied by polymerase chain
      reaction-based restriction analysis. The difference in genotype (chi2=0.24;
      p=0.89) and allelic (Yates' chi2=0.06; p=0.81) frequencies between the groups
      were not significant. Further categorization of the MVP patients into mild and
      severe subgroups also revealed no statistical difference from the controls. It
      was concluded that A/C1166 polymorphism of the AGTR1 gene is not a suitable
      genetic marker of MVPS in Taiwan Chinese.

PMID- 11999642
TI  - Assessment of myocardial perfusion by harmonic power doppler imaging at rest and
      during adenosine triphosphate stress: comparison with coronary flow velocity
      reserve in the left anterior descending coronary arter.
AB  - To clarify whether the myocardial perfusion abnormalities observed on harmonic
      power Doppler imaging (HPDI) during hyperemia are related to a decrease in
      coronary flow velocity reserve (CFVR), HPDI and CFVR were measured in the left
      anterior descending coronary artery (LAD) territory of 75 patients. During
      continuous infusion of Levovist, dual-frame triggered apical 4-chamber views were
      obtained at rest and during adenosine triphosphate (ATP) infusion. The
      persistence of perfusion defects during ATP infusion or stress-induced defects in
      the LAD territory was defined as abnormal. Both HPDI and coronary flow velocity
      recordings of adequate quality were successfully obtained in 73 patients, and 37
      patients showed abnormal myocardial perfusion. CFVR was significantly lower in
      patients with abnormal perfusion than in patients who had normal findings (1.38+/
      0.38 vs 2.60+/-0.76, p<0.001). A CFVR less than 1.9 had a sensitivity of 89%
      (33/37) and a specificity of 89% (32/36) for predicting the presence of abnormal
      myocardial perfusion. This study demonstrates that myocardial perfusion
      abnormalities observed during HPDI using ATP stress are closely correlated to a
      decrease in CFVR and may reflect significant stenosis or microvascular damage in
      the LAD territory.

PMID- 11999643
TI  - Atherosclerotic plaque characterization by quantitative analysis using
      intravascular ultrasound: correlation with histological and immunohistochemical
      findings.
AB  - The aim of this study was to clarify whether atherosclerotic plaque morphology,
      as defined by quantitative analysis with intravascular ultrasound (IVUS) images,
      was related to the immunohistochemical findings. Twenty-five coronary lesions in
      25 patients who had ultrasound guidance during directional coronary atherectomy
      (DCA) were enrolled. The lesions retrieved by DCA were analyzed and divided into
      3 groups (lesions infiltrated with both macrophages and lymphocytes: group IML;
      lesions infiltrated with macrophages but not lymphocytes: group IM; and non
      infiltrated lesions: group NI). The mean plaque echo level divided by the mean
      adventitia echo level (MPEL/MAEL) and the heterogeneity of the distribution of
      plaque echo levels (HDPEL) were calculated. The proportion of patients with acute
      coronary syndromes was significantly different among the groups: IML (n=14), IM
      (n=5), and NI (71%, 0% and 17%, respectively; p<0.01). The pre-DCA HDPEL value
      was highest in group IML and lowest in group NI; however, no significant
      differences in MPEL/MAEL values were found. The results suggest that plaque
      morphology, as defined by IVUS images, was related to the immunohistochemical
      findings. The increase in HDPEL correlated with the presence of immune
      inflammation.

PMID- 11999644
TI  - Fifteen-year trend in the treatment and outcome of acute myocardial infarction in
      Japan.
AB  - To assess the changes in treatment and outcome of acute myocardial infarction
      (AMI) over a 15-year period, the medical records of 1,437 patients with AMI who
      underwent emergency coronary angiography within 24h of the onset of chest pain at
      Hiroshima City Hospital from 1985 to 1999 were reviewed. The patients were
      divided into 3 groups in chronological order: group 1 (1985-89, n=439), group 2
      (1990-94, n=453) and group 3 (1995-99, n=545). Conventional balloon angioplasty
      and thrombolysis were frequently performed in group 1 (56% and 29%, respectively)
      and group 2 (71% and 13%, respectively), whereas coronary stenting and
      conventional balloon angioplasty were more often performed in group 3 (57% and
      23%, respectively). The achievement of TIMI grade 3 flow improved in the
      chronological order (62%, 80% and 85%, respectively; p<0.001). The incidence of
      reinfarction was lower in group 3 (4.2%) than groups 1 and 2 (8.0% and 7.5%,
      respectively; p=0.007), and in-hospital mortality decreased from group 1 to group
      3 (11.8%, 8.2% and 5.5%, respectively; p=0.002). Stenting is now the most
      frequently chosen treatment for AMI and sustained TIMI grade 3 flow is obtained
      in most of the cases, with the result that mortality has reduced by 50% in the
      past decade.

PMID- 11999645
TI  - Cardiac effects of salvia miltiorrhiza/dalbergia odorifera mixture, an
      intravenously applicable Chinese medicine widely used for patients with ischemic
      heart disease in China.
AB  - Chronotropic, inotropic and coronary vasodilator actions of the clinically
      available ampoule preparation of Salvia miltiorrhiza/Dalbergia odorifera mixture
      were examined using canine isolated, blood-perfused heart preparations. The
      mixture slightly decreased the sinoatrial rate and significantly increased
      coronary blood flow, but hardly affected the developed tension of the papillary
      muscle. The effect on coronary blood flow was induced by at least a 10-fold
      smaller dose than that which induced the chronotropic effect. These results were
      quite similar to those of a typical calcium channel blocker, verapamil, used in a
      previous study, suggesting that the Salvia miltiorrhiza/Dalbergia odorifera
      mixture may have potential as an anti-anginal drug.

PMID- 11999646
TI  - Effects of a novel class III antiarrhythmic agent, NIP-142, on canine atrial
      fibrillation and flutter.
AB  - The effects of a new benzopyran derivative, NIP-142, on atrial fibrillation (AF)
      and flutter (AFL) and on electrophysiological variables were studied in the dog.
      NIP-142 (3mg/kg) was administered intravenously to pentobarbital-anesthetized
      beagles during vagally-induced AF and during AFL induced after placement of an
      intercaval crush. Isolated canine atrial tissues were studied using standard
      microelectrode technique. NIP-142 terminated AF in 5 of 6 dogs after an increase
      in fibrillation cycle length (CL) and prevented reinitiation of AF in all 6 dogs.
      NIP-142 terminated AFL in all 6 dogs without any appreciable change in flutter
      CL, and prevented reinitiation of AFL in all 6 dogs. NIP-142 prolonged atrial
      effective refractory periods (11+/-5%, 3+/-3%, 12+/-3%, and 10+/-5% from the
      baseline value at basic CLs of 150, 200, 300, and 350ms, respectively) without
      changes in intraatrial conduction time. The prolongation of the atrial effective
      refractory period was greater in the presence of vagal stimulation. NIP-142
      decreased action potential phase-1 notch and increased phase-2 plateau height
      without making any changes in the action potential duration, although it did
      reverse carbachol-induced shortening of the action potential duration. In
      conclusion, NIP-142 is effective in treating AFL and vagally-induced AF by
      prolonging atrial refractoriness.

PMID- 11999647
TI  - Transmitral inflow pattern assessed by Doppler echocardiography in angiotensin II
      type 1A receptor knockout mice with myocardial infarction.
AB  - Many studies have suggested that the renin-angiotensin system plays an important
      role in the left ventricular (LV) remodeling and cardiac dysfunction that occurs
      after myocardial infarction (MI). Although angiotensin II type IA (AT1A) receptor
      knockout (KO) mice are reported to display less LV remodeling after MI, diastolic
      dysfunction has not been fully evaluated, so the present study measured
      transmitral inflow pattern in both AT1A receptor KO mice with MI (KO-MI) and wild
      type mice with MI (WT-MI). Cardiac geometry and function were examined by Doppler
      echocardiography and myocardial mRNA expression was determined by Northern blot
      analysis at 4 weeks after MI. The LV internal diastolic dimension of WT-MI was
      larger than that of the KO-MI (p<0.05). Marked increases in the E wave velocity
      and the ratio of the peak velocity of the E wave to the A wave were observed in
      the WT-MI (p<0.01). The deceleration rate of the E wave in KO-MI was lower than
      in WT-MI (p<0.05). mRNA expressions of ANP, BNP, collagen I and collagen III in
      the non-infarcted LV and RV of KO-MI were significantly lower than WT-MI. In
      conclusion, transmitral inflow abnormalities in KO-MI were attenuated compared
      with WT-MI.

PMID- 11999648
TI  - Role of medial amygdala in controlling hemodynamics via GABA(A) receptor in
      anesthetized rats.
AB  - Experiments were conducted to determine whether the medial amygdala could control
      hemodynamics through the GABA receptor in anesthetized rats. Bicuculline (10
      100pmol), a GABA(A) antagonist, injected into the anterior basomedial amygdala
      (medial amygdala) produced dose-related increases in blood pressure (BP) and
      heart rate (HR). Following microinjection of a 100pmol dose, plasma
      norepinephrine and epinephrine also rose significantly. In a group that had
      undergone bilateral adrenalectomy, the same dose of bicuculline into the same
      region of the amygdala caused similar increases in BP and HR to those produced in
      normal rats. Pretreatment with an intraperitoneal injection of hexamethonium
      prevented these responses. When bicuculline was given intravenously (100pmol) it
      failed to effect these cardiovascular changes. Bicuculline-induced hypertension
      and tachycardia were inhibited by microinjection of muscimol, a GABA agonist,
      into the anterior basomedial amygdala. The results thus demonstrate that the
      influence of bicuculline on BP and HR is through action on the anterior
      basomedial amygdala and direct sympathetic outflow to heart and vascular smooth
      muscle. There is tonic GABAergic inhibition of sympathetic outflow in the medial
      amygdala that plays a part in regulating hemodynamics in the limbic system.

PMID- 11999649
TI  - Successful planned pregnancy in a patient with St Jude medical prosthetic mitral
      valve.
AB  - A primiparous woman with a St Jude Medical (SJM) mitral valve prosthesis and
      receiving anticoagulant drug delivered a healthy male infant by spontaneous
      normal vaginal delivery. Oral warfarin was replaced by subcutaneous heparin at
      the 6th week of gestation and the dosage of heparin was adjusted to maintain a
      partial thromboplastin time between 2.0 and 2.5 times the control value.
      Treatment with heparin was administered during the first trimester and the last 5
      weeks of gestation. Warfarin was used between the 13th and 32nd week. Successful
      pregnancy and delivery in patients with a SJM mitral valve prostheses is possible
      with careful maintenance of anticoagulation.

PMID- 11999650
TI  - Pulse-spray thrombolysis in acute myocardial infarction caused by thrombotic
      occlusion of an ectatic coronary artery.
AB  - Pulse-spray thrombolysis was performed in 2 patients with acute myocardial
      infarction (AMI) caused by thrombotic occlusion of coronary artery ectasia. Case
      1, a 66-year-old woman with an inferior AMI underwent emergency coronary
      arteriography, which revealed occlusion of an ectatic right coronary artery.
      Primary balloon angioplasty failed to reestablish distal flow. Urokinase was
      administered through the pulse-spray infusion catheter (UltraFuse) and
      intravenous recombinant tissue plasminogen activator was also administered.
      Angiographic disappearance of the thrombus was observed within 30 min of starting
      the infusion, and there was only mild irregularity in the ectatic coronary
      artery. Case 2, a 45-year-old man with an inferior AMI underwent emergency
      coronary arteriography, which revealed occlusion of an ectatic right coronary
      artery. TIMI-3 flow was soon obtained after administration of 480,000 units of
      urokinase through the pulse-spray infusion catheter. There was diffuse right
      coronary ectasia without angiographic evidence of coronary stenosis. Coronary
      ectasia sometimes develops into AMI without the coexistence of coronary stenosis.
      Because a massive thrombus plays a major role, pulse-spray thrombolysis is a
      possible treatment in coronary artery ectasia with thrombotic occlusion.

PMID- 11999651
TI  - Infective endocarditis with perivalvular pseudoaneurysm.
AB  - A 16-year-old Japanese woman with infective endocarditis was admitted to
      hospital. An echocardiography exhibited a perivalvular pseudoaneurysm just under
      the mitral valve. Left ventriculography demonstrated that the aneurysm had a
      small neck and dyskinetic motion with oppression to the coronary sinus and right
      coronary artery.

PMID- 11999652
TI  - Pure right ventricular infarction.
AB  - A 76-year-old man with chest pain was admitted to hospital where
      electrocardiography (ECG) showed ST-segment elevation in leads V1-4, indicative
      of acute anterior myocardial infarction. ST-segment elevation was also present in
      the right precordial leads V4R-6R. Emergency coronary angiography revealed that
      the left coronary artery was dominant and did not have significant stenosis.
      Aortography showed ostial occlusion of the right coronary artery (RCA). Left
      ventriculography showed normal function and right ventriculography showed a
      dilated right ventricle and severe hypokinesis of the right ventricular free
      wall. Conservative treatment was selected because the patient's symptoms soon
      ameliorated and his hemodynamics was stable. 99mTc-pyrophosphate and 201Tl dual
      single-photon emission computed tomography showed uptake of 99mTc-pyrophosphate
      in only the right ventricular free wall, but no uptake of 99mTc-pyrophosphate and
      no perfusion defect of 201Tl in the left ventricle. The peak creatine kinase (CK)
      and CK-MB were 1,381 IU/L and 127 IU/L, respectively. His natural course was
      favorable and the chest pain disappeared under medication. Two months after the
      onset, the ECG showed poor R progression in leads V1-4 indicating an old anterior
      infarction. Coronary angiography confirmed the ostial stenosis of the hypoplastic
      RCA. This was a case of pure right ventricular free wall infarction because of
      the occlusion of the ostium of the hypoplastic RCA, but not of the right
      ventricular branch. Because the electrocardiographic findings resemble those of
      an acute anterior infarction, it is important to consider pure right ventricular
      infarction in the differential diagnosis.

PMID- 11999653
TI  - Circulating hepatocyte growth factor as a diagnostic marker of thrombus formation
      in patients with cerebral infarction.
AB  - Circulating levels of hepatocyte growth factor (HGF) are increased in the early
      stage of an acute myocardial infarction because of arterial thrombosis. The
      purpose of this study was to use a new sensitive enzyme-linked immunosorbent
      assay to investigate whether circulating HGF is increased in patients with
      cerebral infarction. Circulating HGF was measured in 32 patients with cerebral
      infarction on admission to hospital and on days 2, 3, 7 and 14 after the onset of
      symptoms. Serum HGF levels exceeded the mean value +2SD (329pg/ml) measured in
      controls in 10 of 20 patients (50%) within 6 h after onset and in 15 of 32
      patients (47%) within 24 h. Plasma D-dimer was increased in more than half of the
      patients with elevated HGF values. HGF levels in 16 patients who were measured
      serially were persistently increased throughout the study period. The results
      suggests that circulating HGF is a reliable early marker of cerebral infarction,
      and that this new sensitive HGF assay may be useful for diagnosing cerebral
      thrombosis.

PMID- 11999654
TI  - New insights into the role of apoptosis in cardiovascular disease.

PMID- 11999655
TI  - Coronary revascularization in Japan. Part 3: percutaneous coronary intervention
      during 1997.
AB  - A survey by the Japanese Coronary Intervention Study (JCIS) group revealed that
      109,788 percutaneous coronary intervention (PCI) procedures were performed at
      1,023 laboratories during 1997. The present study aimed to describe the
      demographic and clinical characteristics, treatment strategies, in-hospital
      outcomes, and long-term outcomes of these patients. A total of 10,642 PCIs
      performed in 8,814 patients, which corresponded to approximately 10% of the
      overall PCIs, were selected at random. The mean patient age was 65 years, and 75%
      were males. The patients often had extensive coronary risk factors. The most
      prevalent clinical diagnosis was stable angina (36%), followed by myocardial
      infarction (MI) excluding acute myocardial infarction (AMI; 28%) and AMI (25%).
      Plain old balloon angioplasty was used as the sole procedure in 58% of lesions
      for which an attempt to heal was made, and coronary stent placement in 38%.
      Angiographic success was achieved in 92% of attempted lesions. Mortality, MI and
      emergency coronary artery bypass grafting (CABG) rates during the hospitalization
      were 2.6%, 2.0% and 0.7%, respectively. In-hospital mortality rate for AMI was
      7.6%, whereas that for elective PCI in cases without AMI was 0.6%. The overall
      mortality for 1.8 years was 8%. Repeat PCI was performed for 35% and CABG for 6%
      during the follow-up period. In Japan, PCI was performed in patients with
      coronary artery disease and extensive risk factors, but a high rate of
      angiographic success was achieved. The rates of in-hospital mortality and
      emergency CABG were low in non-AMI patients, but the 1-year rate of repeat PCI
      was as high as 32%.

PMID- 11999656
TI  - Partial left ventriculectomy in association with dilated cardiomyopathy:
      echocardiographic follow-up.
AB  - Left ventricular function after a left ventriculectomy was assessed in a patient
      with idiopathic dilated cardiomyopathy (DCM) who has survived longer than any
      other patient in Japan after this operation. The 19-year-old male had a history
      of cerebral infarction because of left ventricular thrombus associated with DCM.
      In order to remove the thrombus and improve left ventricular function, an
      approximately 12x4cm piece of myocardial tissue was resected according to the
      methods of Batista's operation. Left ventricular diastolic dimension was
      temporarily reduced 1 month after surgery, but increased again. During the 45
      months of follow-up, left ventricular diastolic dimension, cardiac output and New
      York Heart Association functional class remain unchanged from the preoperative
      values.

PMID- 11999657
TI  - Unruptured aneurysm of the sinus of valsalva with Behcet's disease.
AB  - A 52-year-old Japanese man who had suffered from Behcet's disease since the age
      of 45 years was admitted to hospital for evaluation of syncope and heart murmur.
      Echocardiography and aortography revealed severe aortic regurgitation and cystic
      masses under the right coronary cusp and the left ventricular outflow tract, but
      no shunt jet. He was diagnosed with unruptured aneurysm of the sinus of Valsalva,
      and surgical closure of the orifice of the aneurysm was performed. The diameter
      of the orifice was 11 mm and the aneurysm was 15 mm in depth, and consisted of 2
      chambers. Because the aortic regurgitation was reduced after patch closure of the
      orifice, aortic valve replacement was not performed. Unruptured aneurysm of the
      sinus of Valsalva is a rare clinical lesion, but patients with active
      inflammatory disease of the aorta, such as in Behcet's disease, should have
      periodic echocardiography for early detection of an aneurysm or valvular
      involvement, even if there are not any symptoms.

PMID- 11999658
TI  - Left atrial thrombus causing pulmonary embolism by passing through an atrial
      septal defect.
AB  - A 66-year-old woman admitted with dyspnea on exertion had atrial fibrillation and
      left ventricular dysfunction. Echocardiography revealed an atrial septal defect
      (ASD) and a soft, easily deformable thrombus in the dilated left atrium. The
      atrial mass suddenly disappeared on the 10th day after admission, and contrast
      enhanced chest computed tomography and pulmonary blood flow scintigraphy showed
      that the thrombus had detached from the left atrium, floated into the right
      atrium through the ASD and caused pulmonary embolism. This is the first
      documented case of a left atrial thrombus causing pulmonary embolism by passing
      through an ASD. When an ASD is present, it is important to consider not only
      paradoxical thromboembolism (from the right to the left atrium), but also
      pulmonary embolism caused by thromboembolism from the left to the right atrium.

PMID- 11999659
TI  - Primary intimal sarcoma of the aorta: role of transesophageal echocardiography.
AB  - Diagnosis of primary tumors of the aorta is difficult. A patient who had a
      primary intimal sarcoma of the aorta with metastasis presented with obstructive
      symptoms and computed tomography showed a thrombus-like mass in the aorta.
      However, transesophageal echocardiography revealed an inhomogeneous and echo
      dense mass with an outer membrane, unlike a thrombus, and suggestive of a primary
      aortic tumor. Pathologic examination of specimens from exploration and autopsy
      revealed a primary intimal sarcoma.

PMID- 11999660
TI  - Increased expression of monocyte chemoattractant protein-1 in atherectomy
      specimens from patients with restenosis after percutaneous transluminal coronary
      angioplasty.
AB  - The plasma concentration of monocyte chemoattractant protein-1 (MCP-1) antigen is
      higher in patients with restenosis after coronary angioplasty than in those who
      do not restenose. In this study the MCP-1 expression of coronary atherectomy
      specimens was investigated by immunohistochemistry. Samples were obtained from 12
      patients with restenosis and 15 with de novo lesions by directional coronary
      atherectomy. MCP-1 immunoreactivity was found in all patients in the restenosis
      group and in 8 of the de novo group. The frequency of macrophage expression was
      higher in the restenosis group than in de novo group. These results indicate that
      local expression of MCP-1 may be associated with the mechanisms of vascular
      remodeling after coronary angioplasty.

PMID- 11999661
TI  - Coronary revascularization in Japan. Part 4: coronary artery bypass surgery
      during 1997.
AB  - The Japanese Coronary Intervention Study (JCIS) has revealed that 17,667 coronary
      artery bypass grafting (CABG) procedures were performed at 477 facilities during
      1997, and this report describes the demographic and clinical characteristics,
      treatment strategies, and the in-hospital and the long-term outcomes in patients
      treated with CABG in Japan. A total of 1,862 CABG cases, which corresponded to
      approximately 10% of the overall CABGs, were selected at random. The mean age was
      65 years, and 76% of cases were males. The most prevalent clinical diagnosis was
      stable angina (54%), followed by myocardial infarction (MI) excluding acute
      myocardial infarction (AMI) (48%), unstable angina (25%), and AMI (5%). A large
      proportion of cases had multivessel coronary artery disease: 3-vessel disease
      (56%) and left main trunk disease (29%). The CABG procedures were emergency in
      16%, and 93% of anastomotic sites were patent. In-hospital mortality and MI
      occurred in 5.1% and 3.5% of cases, respectively. The in-hospital mortality rate
      for emergency CABG was 12.0%, whereas that for elective CABG was 3.8%. The
      overall mortality rate during the follow-up period of 2.3 years was 10%. During
      the follow-up period, MI and angina occurred in 2% and 8% of cases, respectively.
      Percutaneous coronary intervention (PCI) was performed for 8%, and repeat CABG
      for 0.8%. In Japan, CABG was performed in patients with multivessel coronary
      artery disease with extensive risk factors. Angiographically determined success
      was achieved in 93% and the need for subsequent revascularization was relatively
      low.

PMID- 11999662
TI  - Coronary endothelium-dependent and independent vasomotor responses in patients
      with hypertrophic cardiomyopathy.
AB  - It is well known that coronary flow reserve (CFR) is decreased in patients with
      hypertrophic cardiomyopathy (HCM), but it is unclear whether coronary endothelial
      function is impaired. Coronary endothelial function and CFR in the coronary macro
      and microcirculation was evaluated in 14 patients with HCM and 11 control
      subjects. Acetylcholine (ACh), bradykinin (BK) and papaverine were infused into
      the left coronary artery. Coronary cross-sectional area was determined by
      quantitative coronary angiography and coronary blood flow (CBF) was determined by
      the product of the coronary cross-sectional area and CBF velocity measured by an
      intracoronary Doppler guidewire. Acetylcholine at 100 microg induced diffuse
      coronary spasms of the left anterior descending coronary arteries in 3 of the
      patients with HCM. The changes in the diameter of the left anterior descending
      coronary artery and the increases in CBF induced by BK (0.2, 0.6, and 2.0
      microg/min) did not differ between the 2 groups. CFR was lower in the HCM group
      than in the control group (p<0.01). Moreover, the ratio of BK-induced CBF
      increase to papaverine-induced CBF increase was comparable between the 2 groups.
      Endothelium-dependent vasodilation of the epicardial and resistance coronary
      arteries induced by BK was preserved despite the decreased CFR in patients with
      HCM.

PMID- 11999663
TI  - Effects of glucose-induced insulin secretion on ventricular repolarization in
      patients with congenital long QT syndrome.
AB  - To assess the role of insulin in ventricular repolarization in patients with
      congenital long QT syndrome (LQTS), an oral glucose tolerance (OGT) test was
      performed in 11 patients with LQTS and in 11 control cases without QT
      prolongation. Plasma glucose, potassium level and the immunoreactive insulin
      concentration (IRI) were measured, and the QT interval and T wave morphology on
      12-lead ECG were analyzed during fasting and after glucose load. The LQTS group
      had a higher incidence of changes in T wave morphology, such as biphasic, bifid
      or notched T wave, after glucose load than the control group (11 of 11 patients
      [100%] vs 0 of 11 [0%]; p<0.00001). The T wave changes returned to baseline at
      180 min after glucose load in 7 patients. The maximal QT interval and QT
      dispersion increased significantly and returned to baseline level in response to
      IRI after glucose load in LQTS, whereas the QT interval was unaffected in the
      control group. After glucose load, ventricular arrhythmias and T wave alternans
      were observed in 3 and 1 patients with LQTS, respectively, but none in the
      control group. The findings suggest that glucose-induced insulin secretion plays
      a role in inducing abnormalities and inhomogeneity of ventricular repolarization
      in patients with LQTS.

PMID- 11999664
TI  - Clinical significance of iodine-123-15-(p-iodophenyl)-3-R, S-methylpentadecanoic
      acid myocardial scintigraphy in patients with aortic valve disease.
AB  - The present study sought to determine whether myocardial fatty acid metabolism as
      assessed with iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid
      (BMIPP) scintigraphy is impaired in patients with aortic valve disease (AVD) and
      whether the degree of the metabolic abnormality reflects the severity of AVD.
      BMIPP scintigraphy was performed in 12 patients with aortic stenosis (AS), 14
      patients with aortic regurgitation (AR), and 9 healthy volunteers, and from that
      the heart-mediastinum uptake ratio (H/M ratio) corrected by the left ventricular
      (LV) mass (U/Mass ratio) and the myocardial washout rate (WR) were obtained. The
      H/M ratio tended to be higher in patients than in healthy volunteers (3.3 +/- 0.7
      for AS, 3.5 +/- 0.5 for AR, 3.0 +/- 0.3 for healthy volunteers), and the WR was
      significantly higher in patients than in healthy volunteers (42.8 +/- 9.1% for
      AS, 35.7 +/- 6.5% for AR, 19.6 +/- 9.1% for healthy volunteers, p<0.01). In the
      AS patients, the U/Mass ratio showed significant negative correlations (r=-0.79
      to -0.90, all p<0.01) and the WR showed significant positive correlations (r=0.61
      to 0.82, all p<0.01) with transaortic pressure gradient, LV wall thickness, and
      LV mass. Similarly, in AR patients these BMIPP parameters showed proportional
      changes to the LV volumes and LV mass (r=-0.79 to -0.83, all p<0.01 for U/Mass
      ratio, r=0.55 to 0.70, p<0.05 to <0.01 for WR). In the 9 patients who underwent
      aortic valve replacement, the BMIPP parameters tended to normalize with
      increasing U/Mass ratio (0.90 +/- 0.41 x 10(-2)/g to 1.34 +/- 0.59 x 10(-2)/g,
      p<0.05) and decreasing WR (41.9 +/- 8.8% to 35.4 +/- 9.2%, p<0.01) after surgery.
      Myocardial fatty acid metabolism as assessed with BMIPP scintigraphy was impaired
      in patients with aortic valve disease and the U/Mass ratio and WR reflect the
      severity. These parameters may be useful for the noninvasive assessment of the
      myocardial metabolic abnormalities caused by hemodynamic overload.

PMID- 11999665
TI  - Effects of pravastatin on exercise electrocardiography test performance and
      cardiovascular mortality and morbidity in patients with hypercholesterolemia:
      Lipid Intervention Study in Kyoto.
AB  - The long-term effects of the 3-hydoxy-3-methyl-glutaryl coenzyme A reductase
      inhibitor, pravastatin, on exercise electrocardiography (ECG) test performance
      and cardiovascular mortality and morbidity were compared with those of
      conventional lipid-lowering drugs in hypercholesterolemic patients with no
      history of myocardial infarction or stroke. One thousand two hundred and
      seventeen patients were randomly assigned with mean serum cholesterol,
      triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density
      lipoprotein (LDL) cholesterol levels of 6.98 +/- 0.91mmol/L, 2.08 +/- 1.87mmol/L,
      1.38 +/- 0.44mmol/L, and 5.07 +/- 1.14 mmol/L, respectively, and received either
      pravastatin at a dose of 10-20mg/day (group P) or one of the conventional lipid
      lowering drugs such as fibrates, nicotinic acid, and probucol (group C). The
      numbers of patients available for analysis in groups P and C were 305 and 278 at
      year 1, 261 and 216 at year 2, 206 and 184 at year 3, 159 and 122 at year 4, and
      103 and 81 at year 5. Over the 3.2 year mean follow-up period, the reduction in
      serum LDL cholesterol levels was significantly greater (p<0.01) in group P (
      24.3%) than in group C (-16.0%). Serum HDL cholesterol levels increased in group
      P (+11.6%), but decreased in group C (-0.3%) (p<0.01). There were no significant
      differences in the rate of patients who exhibited ischemic changes to exercise
      ECG test (ischemic responders) between the 2 groups. Coronary heart diseases
      (CHD) occurred in 6 patients in group P and 13 in group C; pravastatin
      significantly reduced CHD risk (reduction rate 0.369; 95% confidence interval
      0.140-0.970; p<0.05). No significant differences existed between the treatment
      groups in terms of the number of strokes (group P, 6; group C, 7) or deaths
      unrelated to CHD (group P, 3; group C, 2). Although pravastatin did not improve
      the proportion of ischemic responders on exercise testing, it reduced CHD risk
      and serum LDL cholesterol levels more significantly than conventional lipid
      lowering drugs without adversely affecting the risk of stroke and non-CHD death
      in hypercholesterolemic patients.

PMID- 11999666
TI  - Effects of linear ablation at the isthmus between the tricuspid annulus and
      inferior vena cava for atrial flutter on autonomic nervous activity: analysis of
      heart rate variability.
AB  - Heart rate is largely affected by the autonomic nervous system. However, little
      is known about the anatomic pathway of autonomic nerve fibers innervating the
      sinus node. The present study: (1) evaluates the effects of cavotricuspid isthmus
      ablation for common atrial flutter (AFL) on autonomic nervous function by using
      heart rate variability analysis, and (2) investigates the distribution of
      autonomic nerve pathways innervating the sinus node. Twelve patients with
      paroxysmal common atrial flutter who maintained sinus rhythm both before and
      after radiofrequency ablation were selected for the study. Holter ambulatory
      recordings were performed before and after (2.3 +/- 1.0 days) radiofrequency
      ablation of cavotricuspid isthmus. Heart rate and time domain (SDANN, rMSSD,
      pNN50) and frequency domain (low frequency (LF), high frequency (HF), LF/HF)
      analysis of heart rate variability were compared before and after ablation. Mean
      heart rate did not change significantly after ablation (59 +/- 6 vs 61 +/- 9
      beats/min); parasympathetic indices of heart rate variability (SDANN, rMSSD,
      pNN50, HF) did not change significantly (110 +/- 37 vs 117 +/- 20 ms; 32 +/- 21
      vs 28 +/- 9 ms; 4.8 +/- 0.9 vs 4.7 +/- 0.71n(ms2)); and sympathetic indices of
      heart rate variability (LF/HF) did not change significantly (1.1 +/- 0.2 vs 1.2
      +/- 0.1). Cavotricuspid isthmus ablation for atrial flutter did not significantly
      change heart rate and heart rate variability because parasympathetic and
      sympathetic fibers innervating the sinus node are scarce in this region.

PMID- 11999667
TI  - Tetrahydrobiopterin improves coronary endothelial function, but does not prevent
      coronary spasm in patients with vasospastic angina.
AB  - Reduced bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for
      nitric oxide (NO) synthase, and the resulting decrease in NO in the coronary
      circulation may be involved in the pathogenesis of coronary spasm. The present
      study investigated the effects of BH4 on the vascular response to acetylcholine
      (ACh) in 28 patients with vasospastic angina (VA) using quantitative angiography.
      After recording the vascular responses to ACh (3 and 30 microg/min), either BH4
      (1 mg/min) or saline was infused into the coronary artery for 2 min before and
      during a subsequent infusion of ACh. With the 3 microg/min dose of ACh, BH4
      attenuated the ACh-induced decrease in coronary diameter in both the nonspastic
      segments (-1.1 +/- 2.2% ACh vs 6.0 +/- 2.8% ACh+BH4) and spastic segments (-6.3
      +/- 2.7% ACh vs 2.9 +/- 2.7% ACh+BH4), but did not influence the ACh-induced
      coronary spasm at 30 microg/min (-57.3 +/-2.4% ACh vs -55.3 +/- 2.4% ACh+BH4). In
      the control patients, saline did not influence either the spastic or nonspastic
      vasoconstrictor responses to ACh. Acute administration of BH4 improves coronary
      endothelial function, but does not prevent coronary spasm in patients with VA.

PMID- 11999668
TI  - Dobutamine stress radionuclide ventriculography reveals silent myocardial
      dysfunction in Kawasaki disease.
AB  - Dobutamine (DOB) stress radionuclide ventriculography (RVG) is proposed for
      evaluating left ventricular performance in patients with Kawasaki disease (KD).
      Dobutamine stress RVG, up to 15 microg x kg(-1) x min(-1), was performed in 40
      patients with a history of KD, some of whom had a perfusion defect (PD group) on
      dipyridamole stress thallium-201 myocardial imaging, some of whom had no
      perfusion defects (NPD group), and some of whom had no coronary artery lesions (C
      group). No significant differences in either systolic or diastolic indices of the
      left ventricle at rest were observed between the 3 groups. Although hemodynamic
      responses were similar in all patients after DOB stress, early diastolic index of
      the first third filling fraction decreased only in the PD group and was
      significantly lower in this group compared with the C group (p<0.01). The
      asynchrony index increased significantly in those patients with coronary stenosis
      after DOB stress (p<0.05). No serious side-effects were observed during the
      study. Even late after onset, patients with myocardial ischemia as a result of KD
      still had impaired early diastolic filling and asynchronous relaxation of the
      left ventricle. As an alternative to exercise testing, DOB stress RVG is a safe
      and promising means for serially evaluating left ventricular performance in
      patients with KD.

PMID- 11999669
TI  - Evaluation of bi-atrial pacing and single site right atrial pacing for the
      prevention of atrial fibrillation.
AB  - Atrial resynchronization resulting from simultaneous pacing of the atria may
      adjust inter- or intra-atrial asynchrony and prevent atrial fibrillation (AF).
      The purpose of this study was to assess the efficacy of bi-atrial pacing (BAP) in
      preventing AF, and the safety of this system. The effect of BAP was compared with
      single site right atrial pacing (RAP) in 6 patients with sick sinus syndrome and
      paroxysmal AF in a prospective switchover trial. P wave duration was
      significantly reduced during BAP (p<0.01). Pacing threshold, atrial wave
      amplitude and the lead impedance presented no significant differences at implant,
      1 week and 3 months after implantation, respectively (NS). The number of AF
      episodes significantly decreased during both RAP and BAP compared with the
      control (p<0.01). Although the number of premature atrial contractions was
      significantly less during BAP than RAP (p<0.05), there were no significant
      differences of AF episodes between the two. The percentage of pacing was achieved
      in only 70% during both pacing modes. BAP was safe and reliable in this follow-up
      period and can prevent AF. These findings provide encouragement for further study
      and observation of BAP to prevent AF.

PMID- 11999670
TI  - Ambulatory blood pressure monitoring in Uygur centenarians.
AB  - Cross-sectional surveillance was carried out in long-lived Uygur in China to
      investigate blood pressure (BP) and pulse rate (PR) variation in centenarians.
      The study group comprised 33 centenarians (age > or = 100 years), 103 longevous
      subjects (age 90-99 years) and 100 elderly (age 65-70 years) subjects. Office BP
      was measured, and 24-h noninvasive ambulatory blood pressure monitoring (ABPM)
      was performed. The office BP was higher and hypertension occurred more frequently
      in the centenarians than in either the longevous or elderly subjects. Mean 24-h
      systolic and diastolic BP was higher in the centenarians than in the other 2
      groups. However, mean 24-h PR did not differ between them. Day-night differences
      in systolic BP decreased, and the non-dipper-type BP pattern was common in the
      centenarians (79.1% vs 68% and 63.6% in longevous and elderly subjects,
      respectively). Circadian BP was characterized by 3 peaks in longevous subjects
      and multiple peaks in centenarians. Morning rising and nocturnal dipping of BP
      were observed in both longevous and elderly subjects. In conclusion, BP in
      longevous and elderly Uygur was characterized by circadian rhythmicity, but the
      nocturnal fall in BP was not seen in centenarians. Differences in day-night BP
      and circadian rhythmicity may decrease with advancing age, especially in
      centenarians.

PMID- 11999671
TI  - Cyclical changes in high-energy phosphates during the cardiac cycle by pacing
      Gated 31P nuclear magnetic resonance.
AB  - Whether cyclical changes in energy-related phosphate metabolites arise during a
      cardiac cycle in isolated rat hearts and are affected by differences in myosin
      isozyme composition was determined. Myocardial adenosine triphosphate (ATP),
      phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH in normal,
      hypothyroid and hyperthyroid rat hearts were measured using the pacing-gated 31P
      nuclear magnetic resonance technique. Maximal decrease in ATP and PCr, and
      maximal increase in Pi at the peak-systole in normal rat hearts were observed. In
      hypothyroid and hyperthyroid rats, similar cyclical changes in phosphate
      metabolites were observed during the cycle. However, the magnitude of
      fluctuations was smaller in hypothyroid rats and larger in hyperthyroid rats
      compared with that observed in normal rats. Cardiac myosin isozyme patterns were
      also different amongst the experimental groups. The results suggest that cyclical
      changes and the magnitude of fluctuations in energy-related phosphate metabolites
      during a cardiac cycle may depend on the cardiac workload and the intrinsic
      properties in the enzyme kinetics of myosin.

PMID- 11999672
TI  - Ca2+ overload evokes a transient outward current in guinea-pig ventricular
      myocytes.
AB  - There are 2 types of transient outward currents (Ito) in the hearts of various
      mammals: a 4-aminopyridine (4-AP) sensitive K+ current and a 4-AP resistant Ca2+
      activated current, carried by Cl-, (referred to as I(to1) and I(to2),
      respectively). However, the I(to) has been considered to be absent in guinea-pig
      ventricular myocytes and so this study tested the hypothesis that I(to1) is
      generally absent in guinea-pig ventricular myocytes, but I(to2) appears under the
      condition of Ca2+ overload. Membrane currents were recorded by the whole-cell
      patch-clamp technique and Ca2+ overload was achieved by adding internal, and
      eliminating external, Na+ with subsequent enhancement of Ca2+ influx via the Na+
      Ca2+ exchange. Under physiological conditions, I(to) could not be elicited by 300
      ms-test pulse from -70 mV to 0 mV (n=32). However, under Ca2+ overload, a
      biphasic current resulting from the overlap of the L-type Ca2+ channel current
      and Ito was elicited (n=38). This I(to) was resistant to 4-AP (3 mmol/L, n=30)
      but sensitive to both anthrancene-9-carboxylic acid (9-AC, 3 mmol/L, n=8) and
      4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (100 micromol/L, n=3).
      Replacing K+ with Cs+ on both sides of the membrane failed to abolish I(to)
      (n=38). I(to) disappeared by lowering the external Cl- (n=3). The amplitude of
      I(to) was dependent on that of the L-type Ca2+ channel current (n=4). Because
      Ca2+ release from the sarcoplasmic reticulum was prevented by caffeine (5
      mmol/L), I(to) was negligible (n=6). These results suggest that I(to1) is absent,
      but Ca2+ overload evokes I(to2) in guinea-pig ventricular myocytes.

PMID- 11999673
TI  - Adenosine-induced cardiac gene expression of ischemic murine hearts revealed by
      cDNA array hybridization.
AB  - Because many endogenous substances, including adenosine, contribute to the
      pathophysiology of ischemic hearts, the present study was designed to investigate
      the transcription responses of murine hearts to ischemia with or without
      administration of an inhibitor of adenosine receptor, 8-sulfophenyltheophylline
      (8SPT). Sixty minutes after ligation of the proximal site of the left coronary
      artery with (n=9) or without (n=9) 8SPT, the hearts were excised to obtain mRNA
      for cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10
      fold, and 11 known genes were upregulated 5.0-9.9-fold. 8SPT reduced the
      expressed gene to the control levels. Furthermore, 32 unknown genes were also
      upregulated over 5.0-fold. In contrast, 11 known genes were downregulated below
      0.2-fold, and 64% of the downregulated genes were restored by 8SPT. The 7 unknown
      genes were downregulated to levels below 0.2-fold. Therefore, it was concluded
      that the cardiac expression of 24 known and 39 unknown genes was modulated by
      ischemic stress, and that these genes appeared to be related to the
      pathophysiology of the ischemic heart because endogenous adenosine modulated
      their expression.

PMID- 11999674
TI  - Electrical remodeling of the ventricular myocardium in myocarditis: studies of
      rat experimental autoimmune myocarditis.
AB  - The purpose of this study was to evaluate the electrical remodeling of the
      ventricular myocardium in the experimental autoimmune myocarditis (EAM) model in
      Lewis rats. EAM was induced by immunization with cardiac myosin. During the
      active myocarditis phase, the effective refractory period (ERP), the duration of
      the monophasic action potential (MAPD) was extracted from the left ventricular
      free wall, and the mRNA levels of Kv1.4, 4.2, 4.3 and L type Ca2+ channel were
      determined by RNase protection assays. The inducibility of ventricular arrhythmia
      was higher in EAM rats than in the control rat, and the direct relationship
      between the coupling intervals of the premature stimulus and the ventricular
      arrhythmia in EAM rats. The ERP was prolonged in EAM rats compared with the
      control group. The MAPDs determined as 20% and 90% repolarization time, were both
      longer in EAM rats than in the controls. The level of expression of Kv4.2 mRNA
      was reduced in EAM rats in comparison with the controls, whereas those of Kv1.4,
      4.3 and the L type Ca2+ channel were unchanged. Ventricular vulnerability was
      higher in EAM rats than in the control rats, and some of the ventricular
      arrhythmias observed in the EAM group seemed to be based on triggered activity.
      The level of expression of Kv4.2 mRNA was significantly reduced, and this change
      was compatible with prolongation of the action potential duration.

PMID- 11999675
TI  - Rickets: the third wave.

PMID- 11999676
TI  - A 7-year-old with tachycardia and widened pulse pressure.

PMID- 11999677
TI  - Irritable bowel syndrome and nonspecific diarrhea in infancy and childhood-
      relationship with juice carbohydrate malabsorption.
AB  - Lactose intolerance and malabsorbed carbohydrate present in some fruitjuice may
      trigger symptoms commonly seen in irritable bowel syndrome. In a two-site study,
      28 subjects 9 months to 18 years old (mean 6.9 +/- 5.9 years) with significant
      intake of apple juice or pear nectar (> 6 oz a day) with the diagnoses of
      irritable bowel syndrome, functional abdominal pain, or chronic nonspecific
      diarrhea were recruited. Breath hydrogen tolerance tests utilizing lactose,
      sucrose, and apple juice in the amount they typically consumed were positive in
      32%, 0%, and 50%, respectively. Subjects were asked to refrain from the ingestion
      ofjuice for 1 month: 13 of the 28 (46%) subjects improved while 15 (54%) showed
      no change in their symptoms. In fact, none consuming 6 to 12 oz of apple or pear
      juice daily improved, 27% of those consuming 12 to 16 oz improved, and 91% of
      those consuming > 16 oz improved (P < 0.02). Subjects were then given comparable
      amounts of white grape juice for 1 year. The initial symptoms did not recur in
      any of the subjects who initially responded to the juice-free diet. Of the 15
      subjects who did not respond to the juice-free diet, seven became asymptomatic.
      Overall, 20 subjects (71%) were asymptomatic, and eight (29%) had no change in
      their symptoms. Some individuals with irritable bowel syndrome have their
      symptoms based on their malabsorption of carbohydrates present in apple juice and
      pear nectar and may improve with adequate choices of fruit juice such as changing
      to white grape juice.

PMID- 11999678
TI  - Comparison of the ocular comfort of ofloxacin 0.3% ophthalmic solution and
      lubricant eye drops.

PMID- 11999679
TI  - Clinical findings and resource use of infants and toddlers dependent on oxygen
      and ventilators.
AB  - Medical records were reviewed to describe characteristics, report clinical and
      resource measures, and determine if differences exist between the diagnostic
      groups of prematurity and multiple congenital anomalies/neurologic conditions for
      initial admissions of 37 infants and toddlers to an inpatient pulmonary
      rehabilitation program. More than 75% of the children had a tracheostomy at
      admission and discharge. Forty-six percent of the sample was admitted requiring
      only oxygen, whereas 51% were discharged requiring only oxygen and not mechanical
      ventilation. Thirty percent of the children weaned to a less invasive mode of
      ventilation while just under half of the children were discharged home. Between
      group comparisons indicated statistically significant differences for nutritional
      support at discharge (p < or = 0.05) and discharge disposition (p = 0.04).
      Complete weaning of oxygen or ventilator support during an initial inpatient
      pulmonary rehabilitation admission occurred less frequently than weaning to a
      less invasive mode of ventilation. This is an important consideration for
      referring children to rehabilitation programs, for clinical program improvement
      activities, and for setting realistic expectations for referral sources, patients
      and families, clinical staff, and payers. Further study is recommended using
      clinical data in program planning, in program improvements, and for setting
      outcome expectations for infants and toddlers dependent on pulmonary technology.

PMID- 11999680
TI  - L-carnitine administration reduces number of episodes in cyclic vomiting
      syndrome.
AB  - Patients with cyclic vomiting syndrome suffer from recurring episodes of severe
      nausea and vomiting. This paper presents 6 patients who responded to 1-carnitine
      administration. Average time between episodes was 1.7 months before carnitine
      administration and increased to 1.1 years after carnitine administration. Average
      dose of carnitine administered was 50 mg/kg. Oral carnitine may be useful to
      control the symptoms in patients with cyclic vomiting syndrome.

PMID- 11999681
TI  - Sweet syndrome in infants.

PMID- 11999682
TI  - Abdominal pain with a centrifugal rash.

PMID- 11999683
TI  - Compound heterozygosity for the common sulfonylurea receptor mutations can cause
      mild diazoxide-sensitive hyperinsulinism.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a disorder
      characterized by dysregulation of insulin secretion and prolonged hypoglycemia.
      Mutations in the genes of both subunits of the beta-cell KATP channel, Kir 6.2
      (potassium channel) and SUR1 (sulfonylurea receptor) have been associated with
      the autosomal recessive form of this disorder. It was previously demonstrated
      that patients harboring SUR1 mutations often do not respond well to diazoxide. A
      patient is reported of compound heterozygosity for the 2 most common mutations
      previously reported to be associated with PHHI in Ashkenazi Jews; splice mutation
      of intron 32 (3993-9G-->A) and deletion of phenylalanine at position 1388.
      Relatively low glucose utilization (<10 mg/kg/min) was needed to maintain blood
      gllucose concentrations. In addition, treatment with diazoxide was highly
      effective. We suggest that diazoxide unresponsiveness is not always present in
      patients with SUR1 mutations and that the probable cause of the milder phenotype
      in this compund heterozygote state

PMID- 11999684
TI  - Self-expression through poetry in hypnosis.

PMID- 11999685
TI  - You don't like the taste of your medication? So change the taste!

PMID- 11999686
TI  - A child with severe pneumonia, pleural effusion and acute hypoalbuminemia.

PMID- 11999687
TI  - Salmonella mastitis in a child.

PMID- 11999688
TI  - FRET tells us about proximities, distances, orientations and dynamic properties.

PMID- 11999689
TI  - Kappa-squared: from nuisance to new sense.
AB  - The orientation factor, which is commonly called kappa-squared, is often
      considered to be a nuisance because it represents a significant uncertainty in
      the distance obtained with the FRET technique. It is shown that this uncertainty
      is rather small in almost all cases of practical interest if one takes the width
      of a 67% confidence interval (CI) for the distance distribution as a measure of
      uncertainty. Kappa-squared has the potential to open up new information on
      orientations and rotations from time-resolved studies of donor and acceptor
      anisotropies. One can make sense of such data by designing matrix models for the
      transitions between states describing various orientations and positions of
      donors and acceptors in the system.

PMID- 11999690
TI  - Fluorescence resonance energy transfer studies of U-shaped DNA molecules.
AB  - Fluorescence resonance energy transfer studies allow to determine global shape
      properties of nucleic acids and nucleoprotein complexes. In many DNA-protein
      complexes, the DNA is more or less bent and the degree of bending can be obtained
      by FRET. For example, the DNA in complex with the integration host factor (IHF)
      is kinked by approximately 160 degrees building a U-shaped structure. The two DNA
      helix ends come close to one another in space in a distance range easily
      measurable by FRET. The global DNA structure of this complex can be mimicked by
      introducing two regions with unpaired bases ('bulges') into the DNA each
      producing a sharp kink of approximately 80 degrees. These U-shaped DNA constructs
      were used to measure the electrostatic interaction of the two nearly parallel
      negatively charged DNA helix arms. The electrostatic repulsion between the helix
      arms, and as a consequence their distance, decreases with growing salt
      concentration of mono- or divalent cations. This experimental approach also
      allows the sensitive study of the local structure of DNA sequences positioned
      between the two bulges.

PMID- 11999691
TI  - Fluorescence resonance energy transfer (FRET) and competing processes in donor
      acceptor substituted DNA strands: a comparative study of ensemble and single
      molecule data.
AB  - We studied the fluorescence resonance energy transfer (FRET) efficiency of
      different donor-acceptor labeled model DNA systems in aqueous solution from
      ensemble measurements and at the single molecule level. The donor dyes:
      tetramethylrhodamine (TMR); rhodamine 6G (R6G); and a carbocyanine dye (Cy3) were
      covalently attached to the 5'-end of a 40-mer model oligonucleotide. The acceptor
      dyes, a carbocyanine dye (Cy5), and a rhodamine derivative (JA133) were attached
      at modified thymidine bases in the complementary DNA strand with donor-acceptor
      distances of 5, 15, 25 and 35 DNA-bases, respectively. Anisotropy measurements
      demonstrate that none of the dyes can be observed as a free rotor; especially in
      the 5-bp constructs the dyes exhibit relatively high anisotropy values.
      Nevertheless, the dyes change their conformation with respect to the
      oligonucleotide on a slower time scale in the millisecond range. This results in
      a dynamic inhomogeneous distribution of donor/acceptor (D/A) distances and
      orientations. FRET efficiencies have been calculated from donor and acceptor
      fluorescence intensity as well as from time-resolved fluorescence measurements of
      the donor fluorescence decay. Dependent on the D/A pair and distance, additional
      strong fluorescence quenching of the donor is observed, which simulates lower
      FRET efficiencies at short distances and higher efficiencies at longer distances.
      On the other hand, spFRET measurements revealed subpopulations that exhibit the
      expected FRET efficiency, even at short D/A distances. In addition, the measured
      acceptor fluorescence intensities and lifetimes also partly show fluorescence
      quenching effects independent of the excitation wavelength, i.e. either directly
      excited or via FRET. These effects strongly depend on the D/A distance and the
      dyes used, respectively. The obtained data demonstrate that besides dimerization
      at short D/A distances, an electron transfer process between the acceptor Cy5 and
      rhodamine donors has to be taken into account. To explain deviations from FRET
      theory even at larger D/A distances, we suggest that the pi-stack of the DNA
      double helix mediates electron transfer from the donor to the acceptor, even over
      distances as long as 35 base pairs. Our data show that FRET experiments at the
      single molecule level are rather suited to resolve fluorescent subpopulations in
      heterogeneous mixture, information about strongly quenched subpopulations gets
      lost.

PMID- 11999692
TI  - Time resolved amplification of cryptate emission: a versatile technology to trace
      biomolecular interactions.
AB  - Fluorescence resonance energy transfer (FRET) in association with a time-resolved
      fluorescence mode of detection was used to design a new homogeneous technology
      suitable to monitor biomolecular interactions. A lanthanide cryptate
      characterised by a long lived fluorescence emission was used as donor and a cross
      linked allophycocyanine was used as acceptor. This new donor/acceptor pair
      displayed an exceptionally large Forster radius of 9 nm. This allowed to build up
      a set of labelling strategies to probe the interactions between biomolecules with
      an emphasis on fully indirect cassette formats particularly suitable for high
      throughput screening applications. Herein we describe the basics of the
      technology, review the latest applications to the study of molecular interactions
      involved in cells and new oligonucleotides based assays.

PMID- 11999693
TI  - Applications of fluorescence resonance energy transfer for mapping biological
      membranes.
AB  - The interaction of the cell surface proteins plays a key role in the process of
      transmembrane signaling. Receptor clustering and changes in their conformation
      are often essential factors in the final outcome of ligand receptor interactions.
      Fluorescence resonance energy transfer (FRET) is an excellent tool for
      determining distance relationships and supramolecular organization of cell
      surface molecules. This paper reviews the theoretical background of fluorescence
      resonance energy transfer, its flow cytometric and microscopic applications
      (including the intensity based and photobleaching versions), and provides a
      critical evaluation of the methods as well. In order to illustrate the
      applicability of the method, we summarize a few biological results: clustering of
      lectin receptors, cell surface distribution of hematopoietic cluster of
      differentiation (CD) molecules, and that of the receptor tyrosine kinases,
      conformational changes of Major Histocompatibility Complex (MHC) I molecules upon
      membrane potential change and ligand binding.

PMID- 11999694
TI  - Fluorescence resonance energy transfer analysis of protein-protein interactions
      in single living cells by multifocal multiphoton microscopy.
AB  - Fluorescence resonance energy transfer (FRET) resolved by multifocal multiphoton
      microscopy (MMM) was successfully used to measure transport phenomena in living
      cells. We expressed different pairs of CFP-/YFP-fusion proteins involved in
      retrograde Golgi-to-ER transport to analyze sorting of the occupied KDEL-receptor
      into retrograde transport vesicles triggered by application of the external
      cholera toxin mutant CTXK63. FRET observed as a sensitized emission of the
      acceptor was confirmed by acceptor photobleaching and the dequenching of the
      donor was measured. FRET-MMM data obtained from single cells were compared with
      bulk cell experiments employing spectrofluorimetry. The importance of controlling
      the degree of overexpression of CFP-/YFP-fusion proteins for FRET analysis is
      stressed in this article. Using MMM we showed for the first time that FRET can be
      measured across the Golgi membrane. Finally, FRET-MMM records performed
      continuously over 2 h allowed to analyze intracellular retrograde transport and
      sorting events and to discuss these mechanisms on a single cell level.

PMID- 11999695
TI  - Applications of quantitative PCR in the biosafety and genetic stability
      assessment of biotechnology products.
AB  - High throughput screening, increased accuracy and the coupling of real-time
      quantitative PCR (Q-PCR) to robotic set-up systems are beginning to revolutionise
      biotechnology. Applications of Q-PCR within biotechnology are discussed with
      particular emphasis on the following areas of biosafety and genetic stability
      testing: (a) determination of the biodistribution of gene therapy vectors in
      animals; (b) quantification of the residual DNA in final product therapeutics;
      (c) detection of viral and bacterial nucleic acid in contaminated cell banks and
      final products; (d) quantification of the level of virus removal in process
      validation viral clearance studies; (e) specific detection of retroviral RT
      activity in vaccines with high sensitivity; and (f) transgene copy number
      determination for monitoring genetic stability during production. Methods
      employed for Q-PCR assay validation as required in ICH Topic Q2A Validation of
      Analytical Methods: Definitions and Terminology (1st June 1995) are also
      reviewed.

PMID- 11999696
TI  - Analysis of monohydroxyeicosatetraenoic acids and F2-isoprostanes as markers of
      lipid peroxidation in rat brain mitochondria.
AB  - We have introduced two specific techniques for the quantitative measurement of
      monohydroxyeicosatetraenoic acids (HETEs) and F2-isoprostanes by gas
      chromatography-mass spectrometry/negative ion chemical ionization (GC-MS/NICI) to
      study lipid peroxidation in isolated rat brain mitochondria by iron/ascorbate.
      The analysis of HETEs involved hydrogenation, solid phase extraction on a C18
      cartridge, formation of pentafluorobenzyl bromide and trimethylsilyl ether
      derivatives. In the case of F2-isoprostanes, the analytical procedure was similar
      to that of HETEs except that the hydrogenation step was omitted. We found that
      HETE content (sum of 5-, 8-12-, and 15-isomers) in freshly prepared rat brain
      mitochondria was 220 +/- 40pmol/mg protein. The corresponding content for the F2
      isoprostane, 8-iso-PGF2alpha, was 0.21 +/-+/- 0.10 pmol/mg protein. HETEs and 8
      iso-PGF2alpha were predominantly present in the esterified form. The content of
      both HETEs and 8-iso-PGF2alpha were increased in presence of iron/ascorbate as
      oxidation system. After 30 min incubation with Fe2+ ascorbate, the content of
      HETE isomers was increased about 6-fold compared with baseline levels whereas
      that for 8-iso-PGF2alpha was elevated 100-fold. Formation of HETEs and F2
      isoprostanes corresponded to the consumption of arachidonic acid (AA) and alpha
      tocopherol, respectively. There were almost no changes in the content of free
      (non-esterified) HETEs and 8-iso-PGF2alpha during the course of iron/ascorbate
      induced oxidation of the brain mitochondria. Our data provide the first direct
      evidence for the presence of HETEs and F2-isoprostanes in freshly isolated rat
      brain mitochondria and that esterified HETEs and 8-iso-PGF2alpha are
      predominantly generated during iron/ascorbate induced lipid peroxidation.
      Sensitive quantification of these products of non-enzymatic lipid peroxidation as
      indicators of oxidant injury opens new areas of investigation regarding the role
      of free radicals in the pathogenesis of human diseases. In addition, HETEs and F2
      isoprostanes may be important mediators for mitochondrial functions.

PMID- 11999697
TI  - Vitamin E prevents increase in oxidative damage to lipids and DNA in liver of ODS
      rats given total body X-ray irradiation.
AB  - We examined the effects of dietary vitamin E (VE) on oxidative damage to DNA and
      lipids in the liver a few days after total body irradiation (TBI). ODS rats,
      which lack vitamin C synthesis, were fed either a low VE diet (4.3 mg VE/kg) or a
      basal VE diet (75.6 mg VE/kg) for 5 weeks while vitamin C was supplied in the
      drinking water. The VE level in the liver of the low VE group was lower and the
      levels of lipid peroxides were higher compared to those of the basal VE group:
      the relative levels in the two groups were 1:30 for VE, 18:1 for 4-hydroxynonenal
      (HNE), and 10:1 for hexanal (HA). The level of 8-hydroxydeoxyguanosine (8OHdG), a
      marker of oxidative DNA damage, did not differ between the low VE and the basal
      VE groups. When the rats received TBI at the dose of 3 Gy and were killed on day
      6, the levels of HNE, HA and 8OHdG increased by 2.2-, 2-, and 1.5-times,
      respectively, in the low VE group, but TBI did not cause such increases in the
      basal VE group. Changes in antioxidative enzymes (glutathione peroxidase,
      catalase, and Cu/Zn-SOD) in the liver could not explain the different responses
      of the two diet groups to TBI-induced oxidative damage. The concentrations of
      vitamin C and glutathione in the liver did not differ between the two groups.
      These results suggest that dietary VE can prevent the oxidative damage to DNA and
      lipids in the liver which appear a few days after TBI at dose of 3 Gy.

PMID- 11999698
TI  - Effects of dietary antioxidants on human DNA ex vivo.
AB  - The protective effect of fruits and vegetables against cancer is well
      established. It is believed that this effect is mediated by antioxidants and
      decreased oxidative damage to DNA. However, the identity of the antioxidant(s)
      responsible is not clear. Moreover, a potentially damaging pro-oxidant effect of
      some antioxidants has been reported. In this study the ex vivo effects of several
      dietary antioxidants, including quercetin, various catechins, ascorbic acid and
      alpha-tocopherol, were investigated, at concentrations up to 200 microM, using
      the single cell gel electrophoresis (comet) assay for DNA damage. Lymphocytes
      from three healthy subjects were pre-incubated with these antioxidants, and the
      comet assay was performed on treated, untreated, challenged and unchallenged
      cells in parallel, oxidant challenge being induced by 5 min exposure to hydrogen
      peroxide (final concentrations H2O2: 30, 45, or 60 microM). Results using this ex
      vivo cellular assay showed protection by some antioxidants (quercetin, caffeic
      acid), no effect by some (catechin, epicatechin, catechin gallate, epicatechin
      gallate) and an apparently damaging effect by others (epigallocatechin,
      epigallocatechin gallate). Damage may have been caused by production of H2O2 from
      these polyphenolics. Neither ascorbic acid nor alpha-tocopherol protected or
      damaged DNA. Further study of the role of quercetin and caffeic acid in DNA
      protection is needed.

PMID- 11999699
TI  - Oxidative deamination by hydrogen peroxide in the presence of metals.
AB  - Various amines, including lysine residue of bovine serum albumin, were
      oxidatively deaminated to form the corresponding aldehydes by a H2O2/Cu2+
      oxidation system at physiological pH and temperature. The resulting aldehydes
      were measured by high-performance liquid chromatography. We investigated the
      effects of metal ions, pH, inhibitors, and O2 on the oxidative deamination of
      benzylamine by H202. The formation of benzaldehyde was the greatest with Cu2+,
      and catalysis occurred with Co2+, VO2+, and Fe3+. The reaction was greatly
      accelerated as the pH value rose and was markedly inhibited by EDTA and catalase.
      Dimethyl sulfoxide and thiourea, which are hydroxyl radical scavengers, were also
      effective in inhibiting the generation of benzaldehyde, indicating that the
      reaction is a hydroxyl radical-mediated reaction. Superoxide dismutase greatly
      stimulated the reaction, probably due to the formation of hydroxyl radicals. O2
      was not required in the oxidation, and instead slightly inhibited the reaction.
      We also examined several oxidation systems. Ascorbic acid/O2/Cu2+ and
      hemoglobin/H2O2 systems also converted benzylamine to benzaldehyde. The proposed
      mechanism of the oxidative deamination by H2O2/Cu2+ system is discussed.

PMID- 11999700
TI  - Adaptation to multiday ozone exposure is associated with a sustained increase of
      bronchoalveolar uric acid.
AB  - The phenomenon of ozone tolerance is described, but the underlying mechanisms
      remain unknown. We tested whether adaptation to multiday ozone exposure was
      related to an upregulated pulmonary antioxidant defence. Six calves were exposed
      to 0.75 ppm ozone, 12 h day(-1) for seven consecutive days. Pulmonary function
      tests and bronchoalveolar lavage (BAL) were performed before, after the first
      (D1), third (D3) and seventh (D7) exposure. Differential cell count, total
      proteins, 8-epi-PGF2alpha, glutathione and uric acid were determined in BAL.
      Dynamic lung compliance and arterial oxygen tension were significantly decreased
      and lung oedema impaired pulmonary function on D1. By repeating ozone exposures,
      progressive functional adaptation occurred. Ozone induced a significant increase
      of BAL neutrophil percentage on D1. On D3 and D7, neutrophil percentage was
      progressively decreased, but remained significantly elevated. BAL total proteins
      were significantly increased on D1 and decreased progressively until D7. 8-Epi
      PGF2alpha was significantly increased on D1 and was returned to baseline on D3
      and D7, whilst glutathione significantly increased on D3 and returned to baseline
      on D7. Uric acid was increased ten-fold on D1. On D3, uric acid was increased six
      fold and was persistently elevated at D7. This study suggests that ozone
      adaptation of functional and inflammatory variables is accompanied with sustained
      BAL uric acid elevation.

PMID- 11999701
TI  - N-acetylcysteine improves in vitro the function of macrophages from mice with
      endotoxin-induced oxidative stress.
AB  - Reactive oxygen species (ROS) and proinflammatory cytokines produced by immune
      cells cause the oxidative stress involved in septic shock induced by endotoxin.
      This oxidative stress can be controlled to a certain degree by antioxidants,
      which is specially important for a type of immune cell, i.e. the phagocyte, that
      uses ROS to kill microorganisms and needs antioxidants in order to support its
      functions. In a previous study we have observed changes in several functions of
      peritoneal macrophages from BALB/c mice with lethal endotoxic shock caused by
      intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) (100
      mg/kg), which were associated with a high production of superoxide anion. N
      acetylcysteine (NAC) is a thiolic antioxidant that improves the immune response,
      and we have observed that when administered intraperitoneally (150 mg/kg) at 30
      min after LPS injection it counteracts the effects of LPS on macrophages and
      lymphocytes. In the present work, we have studied the in vitro effect of several
      concentrations of NAC (0.001, 0.01, 0.1, 1 and 2.5 mM) on the following
      functions: adherence to substrate, chemotaxis, ingestion of particles, ROS
      production and the release of tumor necrosis factor (TNFalpha) of peritoneal
      macrophages from BALB/c mice at 2, 4,12 and 24 h after LPS injection. The results
      show that the administration of NAC (especially at 0.1 mM) decreases raised
      adherence, ingestion, ROS production and TNFalpha levels in macrophages from
      animals injected with LPS, bringing these functions to values near those of
      control animals. These effects which seem to be linked to a modulation of NF
      kappaB, suggest that the improvement of immune functions observed in previous
      work after injection of NAC to animals with endotoxic shock could be due to a
      direct action of this thiol antioxidant on immune cells.

PMID- 11999702
TI  - Aging increases Nepsilon-(carboxymethyl)lysine and caloric restriction decreases
      Nepsilon-(carboxyethyl)lysine and Nepsilon-(malondialdehyde)lysine in rat heart
      mitochondrial proteins.
AB  - The present investigation studies the effect of aging, short-term and long-term
      caloric restriction on four different markers of oxidative, glycoxidative or
      lipoxidative damage to heart mitochondrial proteins: protein carbonyls (measured
      by ELISA); Nepsilon-(carboxyethyl)lysine (CEL), Nepsilon-(carboxymethyl)lysine
      (CML), and Nepsilon-(malondialdehyde)lysine (MDA-lys) measured by gas
      chromatography/mass spectrometry. Aging increased the steady state level of CML
      in rat heart mitochondria without changing the levels of the other three markers
      of protein damage. Short-term caloric restriction (six weeks) did not change any
      of the parameters measured. However, long-term (one year) caloric restriction
      decreased CEL and MDA-lys in heart mitochondria and did not change protein
      carbonyls and CML levels. The decrease in MDA-lys was not due to changes in the
      sensitivity of mitochondrial lipids to peroxidation since the measurements of the
      fatty acid composition showed that the total number of fatty acid double bonds
      was not changed by caloric restriction. The decrease in CEL and MDA-lys in
      caloric restriction agrees with the previously and consistently described finding
      that caloric restriction agrees with the previously and consistently described
      finding that caloric restriction lowers the rate of generation of reactive oxygen
      species (ROS) in rodent heart mitochondria, although in the case of CEL a caloric
      restriction-induced lowering of glycaemia can also be involved. The CEL and MDA
      lys results support the notion that caloric restriction decreases oxidative
      stress-derived damage to heart mitochondrial proteins.

PMID- 11999703
TI  - Oxidative DNA base damage, antioxidant enzyme activities and selenium status in
      highly iodine-deficient goitrous children.
AB  - The objective of this study was to investigate oxidative DNA damage, and the
      levels of antioxidant enzymes (AOE) and selenium (Se) in relation to iodine
      deficiency and/or goiter in children. The study was performed in a group of
      goitrous high school children (15-18 years of age) (n = 14) with severe or
      moderate iodine deficiency. Thyroid hormones (TSH, FT4, TT4, FT3, TT3), urinary
      iodine (UI) and plasma Se levels, and erythrocyte glutathione peroxidase (GSHPx),
      superoxide dismutase (SOD) and catalase (CAT) activities were determined and
      compared with those of a control group consisting of non-goitrous high school
      children (n = 14) with normal UI levels or mild iodine deficiency. In the
      goitrous group, concentrations of FT4, TT4, plasma Se and UI, and activities of
      GSHPx and SOD were found to be significantly lower. Six typical hydroxyl radical
      induced base lesions in genomic DNA of peripheral blood were identified and
      quantified by gas chromatography/isotope-dilution mass spectrometry (GC/IDMS),
      and higher levels of DNA base lesions were observed in the goitrous group. The
      results suggest that highly iodine-deficient goitrous children may be under
      oxidative stress, which may lead to greater level of oxidative damage to DNA.
      This study supports the evidence for the reported relationship between iodine
      deficiency and the increased incidence of thyroid malignancies.

PMID- 11999704
TI  - Assessment of in vivo oxidative lipid metabolism following acute microcystin-LR
      induced hepatotoxicity in rats.
AB  - Oxidative lipid metabolism as a result of acute cyanobacterial toxin-induced
      hepatotoxicity was monitored in male Sprague-Dawley rats using electron spin
      resonance (ESR) spectroscopy and image-guided proton nuclear magnetic resonance
      (1H-NMR) spectroscopy. ESR spectroscopy, coupled with spin trapping, was used to
      trap and detect lipid-derived radicals, formed in rat livers after acute in vivo
      exposure (LD50) to the cyanobacterial toxin, microcystin-LR (MCLR). A
      statistically significant increase in the levels (spectral peak integrals) of
      lipid radicals was detected in MCLR-treated livers (p < 0.05) (n = 8), in
      comparison to control livers (n = 6). In order to monitor lipid metabolism,
      before and for a period of 3 h, following toxin exposure, in vivo proton image
      guided NMR spectroscopy was used. A statistically significant decrease in the
      levels of lipid methylene hydrogen resonances (spectral peak integrals) was
      observed from MCLR-treated livers (n = 6) 2 and 3 h post-exposure (p < 0.05), in
      comparison to controls (n = 6). Image-guided NMR spectroscopy was also used to
      detect significant decreasing levels of in vivo glutamine/glutamate, following
      exposure to MCLR. Biochemical assessment of perchloric extracts of liver
      glutamine and glutamate levels correlated with NMR spectroscopy results. Lactate
      levels measured as perchloric acid extracts, were also found to significantly
      decrease. In addition, assessment of serum enzymes alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) levels were used to confirm hepatotoxicity
      (n = 20). This study strongly suggests that oxidative stress related processes
      are involved in in vivo microcystin-induced hepatotoxicity in mammals, and may
      play an integral role in MCLR-induced toxicity.

PMID- 11999705
TI  - Thiol-linked peroxidase activity of human sensitive to apoptosis gene (SAG)
      protein.
AB  - SAG (sensitive to apoptosis gene), a novel zinc RING finger protein, which is
      redox responsive and protects mammalian cells from apoptosis, is a metal chelator
      and a potential reactive oxygen species (ROS) scavenger, but its antioxidant
      properties have not been completely defined. Here, we show that SAG possesses a
      potent peroxidase property to decompose hydrogen peroxide in the presence of
      dithiothreitol (DTT). However, without DTT as a reducing equivalent, SAG was not
      able to destroy hydrogen peroxide. The peroxidase activity was completely
      abolished by the reaction of SAG with N-ethylmaleimide (NEM), a chemical
      modification agent for the sulfhydryl of proteins. These observations suggested
      that the sulfhydryl of cysteines in SAG could function as strong nucleophiles to
      destroy hydrogen peroxide. In addition to the peroxidase activity used to remove
      hydrogen peroxide, SAG also showed t-butylhydroperoxide (t-BOOH) and fatty acid
      hydroperoxide-selective peroxidase activity.

PMID- 11999706
TI  - Poly(ADP-ribose) polymerase activation and cell injury in the course of rat heart
      heterotopic transplantation.
AB  - Free radicals and other reactive species generated during reperfusion of ischemic
      tissues may cause DNA damage and, consequently, the activation of the nuclear
      enzyme poly(ADP-ribose) polymerase (PARP). An excessive PARP activation may
      result in a depletion of intracellular NAD+ and ATP, hence cell suffering and,
      ultimately, cell death. The present study is aimed at clarifying the role of PARP
      in a heart transplantation procedure and the contribution of myocyte necrosis
      and/or apoptosis to this process. In our experimental model, rat heart subjected
      to heterotopic transplantation, low temperature global ischemia (2 h) was
      followed by an in vivo reperfusion (30 or 60 min). Under these conditions clear
      signs of oxidative stress, such as lipoperoxidation and DNA strand breaks, were
      evident. In addition to a marked activation, accompanied by a significant NAD+
      and ATP depletion, PARP protein levels significantly increased after 60 min of
      reperfusion. Ultrastructural analysis showed nuclear clearings, intracellular
      oedema and plasma membrane discontinuity. Other relevant observations were the
      absence of typical signs of apoptosis like caspase-3 activation and PARP
      cleavage, random DNA fragmentation, rise in serum levels of heart damage markers.
      Our results suggest that during heart transplantation, the activation of PARP,
      causing energy depletion, results in myocardial cell injury whose dominant
      feature, at least in our experimental model, is necrosis rather than apoptosis.

PMID- 11999707
TI  - Exposure to malondialdehyde induces an early redox unbalance preceding membrane
      toxicity in human erythrocytes.
AB  - This work investigated the oxidative injury to human red blood cells (RBCs) by
      the exposure to exogenous malondialdehyde (MDA), in a physiological environment.
      When a 10% RBC suspension was incubated in autologous plasma, in the presence of
      50 microM MDA, 30% of MDA entered into the cells. A time-course study showed that
      MDA caused early (30-120 min) and delayed (3-18 h) effects. MDA caused a fast
      depletion of reduced glutathione, and loss of the glucose-6-phosphate
      dehydrogenase activity, followed by a decrease of HbO2. Accumulation of
      methemoglobin, and formation of small amounts of hemichrome were later evident.
      Also, an HbO2-derived fluorescent product was measured in the membrane. The redox
      unbalance was followed by structural and functional damage to the membrane,
      evident as the formation of conjugated diene lipid hydroperoxides, concurrent
      with a sharp accumulation of MDA, consumption of membrane vitamin E, and egress
      of K+ ions. SDS--PAGE of membrane proteins showed formation of high molecular
      weight aggregates. In spite of the marked oxidative alterations, the incubation
      plasma prevented a substantial hemolysis, even after a 18 h incubation. On the
      contrary, the exposure of RBCs to 50 microM MDA in glucose-containing phosphate
      saline buffer, resulted in a 16% hemolysis within 6 h. These results indicate
      that the exposure to MDA causes a rapid intracellular oxidative stress and
      potentiates oxidative cascades on RBCs, resulting in their dysfunction.

PMID- 11999708
TI  - Toxicity of cadmium in tobacco smoke: protection by antioxidants and chelating
      resins.
AB  - The effects of cadmium, an environmental toxin present in tobacco smoke, were
      studied in vitro in human monocytes and compared to those of tobacco smoke.
      Overexpression of the 72kDa heat shock/stress protein Hsp70 and cell death
      occurred with a similar time-course and to a similar extent in human monocytes
      exposed to either cadmium or tobacco smoke. Cadmium and tobacco smoke-mediated
      toxicity were associated with a decrease in the cellular content of glutathione
      and ATP and the glutathione precursor N-acetyl-L-cysteine prevented both cadmium
      and tobacco smoke-mediated toxicity. Furthermore, tobacco smoke-mediated toxicity
      was prevented by pretreatment with the cadmium chelator resin Chelex-100,
      supporting the conclusion that cadmium plays a major role in tobacco smoke
      mediated toxicity.

PMID- 11999709
TI  - Biomolecular nanotechnology.

PMID- 11999710
TI  - Detection and characterization of single biomolecules at surfaces.
AB  - The investigation of bio-molecules has entered a new age since the development of
      methodologies capable of studies at the level of single molecules. In biology,
      most molecules show a complex dynamical behavior, with individual motions and
      transitions between different states, occurring as highly correlated in space and
      time within an arrangement of various elements. In order to resolve such
      dynamical changes in ensemble average techniques, one would have to synchronize
      all molecules, which is hard to achieve and might interfere with important system
      properties. Single molecule studies, in contrast, do not require pretreatment of
      the system and resume, therefore, much less invasive methodologies. Here, we
      review recent employments for the investigation of bio-molecules on surfaces, in
      which the high local and temporal resolution of two complementary techniques,
      atomic force microscopy and single molecule fluorescence microscopy, is used to
      address single molecules. Novel methodologies for the characterization of
      biologically relevant parameters, functions and dynamical aspects of individual
      molecules are described.

PMID- 11999711
TI  - Single molecule research on surfaces: from analytics to construction and back.
AB  - The study of single molecules opens a new dimension in understanding nature down
      to its finest ramifications. While much progress was achieved in the last decade
      concerning the detection techniques, suitable techniques for manipulating and
      handling the biomolecules still bear a challenge. Primarily, the task is keeping
      an individual, active molecule of a certain lifespan in the spot. Here, we will
      focus on techniques for the functional immobilization of (single) molecules on
      surfaces to enable their observation at one position over a time period.
      Presenting the main methods of reversible immobilization we will accentuate the
      chelator lipid concept as combining all features prerequisite for functional,
      reversible and well-defined immobilization. This will also show that single
      molecule research in principle is the synthesis of an insight into the function
      of nature and nano-biotechnology (manipulation): thus of analytics, construction,
      and back.

PMID- 11999712
TI  - DNA-gold conjugates for the detection of specific molecular interactions.
AB  - DNA chips are an emerging technology for parallel detection of DNA molecules,
      with applications ranging from medicine to environmental monitoring. The typical
      set-up includes fluorescence labeling for detection of binding events on the chip
      surface. Here another labeling technique based on gold nanoparticles is
      presented. These labels are much more stable, and their optical signal is less
      influenced by the environment. The specificity of gold-labeled DNA probes and the
      ease of detection using optical reflection or transmission is demonstrated. In
      conclusion, gold-labeling is a promising candidate for more robust and reliable
      DNA-chip detection.

PMID- 11999713
TI  - Semi-synthetic nucleic acid-protein conjugates: applications in life sciences and
      nanobiotechnology.
AB  - Semi-synthetic conjugates of nucleic acids and proteins can be generated by
      either covalent coupling chemistry, or else by non-covalent biomolecular
      recognition systems, such as receptor-ligands of complementary nucleic acids.
      These nucleic acid-protein conjugates are versatile molecular tools which can be
      applied, for instance, in the self-assembly of high-affinity reagents for
      immunological detection assays, the fabrication of laterally microstructured
      biochips containing functional biological groups, and the biomimetic 'bottom-up'
      synthesis of nanostructured supramolecular devices. This review summarizes the
      current state-of-the-art synthesis and characterization methods of artificial
      nucleic acid-protein conjugates, as well as applications and perspectives for
      future developments of such hybrid biomolecular components in life sciences and
      nanobiotechnology.

PMID- 11999714
TI  - Molecular shuttles based on motor proteins: active transport in synthetic
      environments.
AB  - Active transport in cells, utilizing molecular motors like kinesin and myosin,
      provides the inspiration for the integration of active transport into synthetic
      devices. Hybrid devices, employing motor proteins in a synthetic environment, are
      the first prototypes of molecular shuttles. Here the basic characteristics of
      motor proteins are discussed from an engineering point of view, and the
      experiments aimed at incorporating motor proteins, such as myosins and kinesins,
      into devices are reviewed. The key problems for the construction of a molecular
      shuttle are: guiding the direction of motion, controlling the speed, and loading
      and unloading of cargo. Various techniques, relying on surface topography and
      chemistry as well as flow fields and electric fields, have been developed to
      guide the movement of molecular shuttles on surfaces. The control of ATP
      concentration, acting as a fuel supply, can serve as a means to control the speed
      of movement. The loading process requires the coupling of cargo to the shuttle,
      ideally by a strong and specific link. Applications of molecular shuttles can be
      envisioned, e.g. in the field of nano-electro-mechanical systems (NEMS), where
      scaling laws favor active transport over fluid flow, and in the bottom-up
      assembly of novel materials.

PMID- 11999715
TI  - Glial perspectives.

PMID- 11999716
TI  - Regulation and expression of progesterone receptor mRNA isoforms A and B in the
      male and female rat hypothalamus and pituitary following oestrogen treatment.
AB  - Progesterone receptors play a central role in neuroendocrine and behavioural
      regulation. To gain insight into the sex- and tissue-specific regulation of
      progesterone receptors, protein binding on a progesterone receptor-oestrogen
      response element and mRNA levels for progesterone receptor (PR)-A and PR-B were
      compared between female and male rats following oestradiol benzoate replacement
      treatment in hypothalamic and pituitary tissue. Both male and female pituitary
      protein extracts demonstrated an increase in nuclear protein binding activity to
      a progesterone receptor-oestrogen response element following oestradiol benzoate
      treatment. However, there was a greater difference in total binding activity seen
      in the female pituitary extracts compared to male pituitary protein extracts. In
      both cases, reflecting the binding data, oestradiol benzoate pretreatment led to
      an increase in pituitary PR-B messenger RNA, although this increase was
      significantly larger in females than in males. Oestradiol benzoate treatment also
      led to a significant increase in specific binding of hypothalamic nuclear
      proteins to the progesterone receptor oestrogen response element from both
      females and male hypothalamic extracts. In addition, PR-B messenger RNA was
      induced by oestradiol benzoate treatment in the female rat hypothalamus, under
      circumstances where no PR-A could be detected. The male also demonstrated an
      increase in PR-B messenger RNA following oestradiol benzoate treatment, with
      undetectable levels of PR-A, although to a lesser degree than that seen in the
      female. The predominance of PR-B over PR-A messenger RNA in rat hypothalamus and
      pituitary, and the quantitative differences between female and male rats, could
      both contribute to the greater responsiveness of female rats to progesterone with
      respect to control over luteinizing hormone release from the pituitary, and
      lordosis behaviour regulated by hypothalamic neurones.

PMID- 11999717
TI  - Thyrotropin-releasing hormone-induced down-regulation of pyroglutamyl
      aminopeptidase II activity involves L-type calcium channels and cam kinase
      activities in cultures of adenohypophyseal cells.
AB  - Released thyrotropin-releasing hormone (TRH) is inactivated by a narrow
      specificity ectopeptidase, pyroglutamyl aminopeptidase II (PPII), present in
      brain and lactotrophs. Various hypothalamic/paracrine factors, including TRH,
      slowly (in hours) regulate the activity of PPII on the surface of
      adenohypophyseal cells. TRH-induced down-regulation was mimicked by protein
      kinase C (PKC) activation but was not affected by inhibition of PKC. Adenylate
      cyclase activation can also down-regulate PPII. The purpose of this study was to
      identify elements of the transduction pathway used by TRH to regulate PPII
      activity. In primary cultures of female adenohypophyseal cells, activation of the
      stimulatory G protein or adenylate cyclase produced an effect additive to that of
      TRH; inhibition of protein kinase A activity did not interfere with TRH action.
      However, regulation of PPII activity by TRH was inhibited by a phospholipase C
      beta inhibitor or chelation of intracellular calcium. L-type calcium channels
      (LCC) agonists mimicked TRH action and their effect was not additive with that of
      TRH. Antagonists of LCC channels and inhibitors of calmodulin or
      calcium/calmodulin-dependent protein kinase blocked TRH action. Therefore, TRH
      induced calcium entry through L-type calcium channels and the activity of
      calcium/calmodulin-dependent protein kinase are required for TRH effect on PPII
      activity in primary cultures of adenohypophyseal cells. This pathway may
      coregulate PPII and prolactin biosynthesis in response to TRH.

PMID- 11999718
TI  - Melatonin modulates [3h]serotonin release in the rat hippocampus: effects of
      circadian rhythm.
AB  - Serotonin (5-HT) participates as a neurotransmitter in the control of the
      circadian sleep/wake rhythm, feeding and sexual behaviours, and emotional and
      affective states. The present study investigated whether melatonin affects the
      circadian rhythm of 5-HT neurotransmission in the hippocampus, a major target for
      serotoninergic antidepressants. The present results show a daytime dependency of
      [3H]5-HT uptake insensitive to melatonin, with a peak from 14.00 h to 22.00 h and
      a trough from 02.00 h to 06.00 h. They also indicate that melatonin reduced the
      spontaneous efflux of [3H]5-HT as well as KCl-evoked release of [3H]5-HT during
      the dark phase, while it increased the evoked release during the light phase.
      Both effects were concentration-dependent; the facilitatory effect was maximum at
      high nanomolar concentrations of melatonin, whereas the inhibition preferentially
      occurred at low concentrations. Finally, nifedipine, an effective antagonist of L
      type voltage-sensitive calcium channels, prevented the effects of melatonin on
      KCl-evoked [3H]5-HT release during the light but not the dark phase. Together,
      these data suggest the involvement of two distinct mechanisms by which melatonin
      might regulate both spontaneous efflux and evoked release of 5-HT in the
      hippocampus.

PMID- 11999719
TI  - Effect of adrenergic blockade on the pheromonal restoration of cyclic activity in
      young oestrogen-primed persistent oestrous female rats.
AB  - The effects of adrenergic blockade on pheromonal restoration of cyclic activity
      were studied in acute oestrogenized persistent oestrous young female rats.
      Hypothalamic luteinizing hormone-releasing hormone (LHRH) and plasma LH, follicle
      stimulating hormone (FSH), oestradiol and progesterone were measured by specific
      radio-immunoassays, and prolactin by enzyme-linked immunosorbent assay in: (i)
      young cycling rats; (ii) young persistent oestrous female rats; (iii) young
      persistent oestrous females treated with nasal sprays of male urine; and (iv)
      young persistent oestrous females treated with nasal sprays of male urine and
      injected with saline, propranolol, prazosin or yohimbine. LHRH was low 24 h after
      oestradiol benzoate injection, increasing up to 15 days later; LH, FSH,
      oestradiol and progesterone ranged from high values 24 h after oestradiol
      benzoate injection to low 15 days later; prolactin ranged from low concentration
      24 h after oestradiol benzoate injection to high 15 days later. Male urine
      treatment induced a depletion of LHRH, a rise of LH, FSH and progesterone,
      pheromonal restoration of cyclic activity and a normal hormonal cyclic pattern.
      Treatment with prazosin and yohimbine prevented the pheromonal restoration of
      cyclic activity, the drop of LHRH and the rise of plasma concentration of the
      studied hormones induced by male urine, while saline or propranolol did not.
      These results show the hormonal pattern of the pheromonal restoration of cyclic
      activity in persistent oestrous rats and strongly suggest that alpha-adrenergic
      inputs to the hypothalamus may be involved in this pheromonal effect.

PMID- 11999720
TI  - Distribution of gonadotropin-releasing hormone neurones in the chick forebrain is
      independent of lineage relationships among cells of the early nasal placode.
AB  - The regulation of reproduction depends upon the successful migration of
      gonadotropin-releasing hormone (GnRH) neurones from the nasal placode to the
      ventral forebrain during embryogenesis. Within the central nervous system (CNS),
      these neurones migrate to stereotyped, highly reproducible locations in septal,
      preoptic and hypothalamic nuclei. We postulated that lineage relationships
      (descent from a common precursor) might predict the final location of these
      neurones. To test this hypothesis, a complex retroviral library was used to label
      dividing cells in the placode and subsequently to identify them by the presence
      of the alkaline phosphatase marker. GnRH was detected immunocytochemically and
      lineage relationships determined by single cell polymerase chain reaction and
      sequencing of the degenerate oligonucleotide component of the retrovirus. GnRH
      positive and GnRH-negative neurones were confined to the side ipsilateral to the
      injection; many cells derived from the placode that entered the CNS did not
      contain GnRH. This precise method of identifying and mapping the progeny of
      single neurones revealed that GnRH cells in any given area were derived from
      multiple precursors. This developmental pattern may contribute to assuring that
      all CNS locations critical to the orchestration of reproductive events will be
      populated by GnRH neurones.

PMID- 11999721
TI  - Somatosensory stimuli evoke norepinephrine release in the anterior ventromedial
      hypothalamus of sexually receptive female rats.
AB  - We used in vivo brain microdialysis to determine the role of specific copulatory
      stimuli in mating-induced release of norepinephrine in the lateral ventromedial
      hypothalamus (VMH) of hormone-treated, sexually receptive female rats.
      Ovariectomized rats implanted with a unilateral guide cannula aimed at the
      ventrolateral VMH received systemic injections of estradiol benzoate daily for 2
      days before and progesterone 4 h before the initiation of a 1-h behavioural test.
      Dialysis probes were lowered immediately after progesterone administration, and
      20-min dialysis samples were collected until 1 h after the termination of
      behavioural testing. Norepinephrine content of dialysates was quantified by high
      performance liquid chromatography with electrochemical detection. During mating
      tests with male rats, dialysate levels of norepinephrine increased significantly
      over baseline in sexually receptive females with probe placements in the anterior
      but not posterior VMH. Norepinephrine levels were unchanged if rats were
      nonreceptive, even if males mounted vigorously and probes were located in the
      anterior VMH. Hormone-treated females that were placed on male-soiled bedding for
      1 h showed no changes in dialysate levels of norepinephrine. Similarly, females
      in which vaginocervical stimulation was prevented by a vaginal mask failed to
      show increased levels of norepinephrine in dialysates collected from the anterior
      VMH, even if they displayed high levels of lordosis behaviour. Thus, the release
      of norepinephrine is not a result of executing the lordosis posture. The findings
      suggest that mating-induced increases in norepinephrine release in hormone
      treated, sexually receptive rats are confined to the anterior VMH and that
      somatosensory rather than chemosensory stimuli evoke norepinephrine release.
      Moreover, experiments with vaginal masks indicate that vaginocervical stimulation
      is necessary for mating-evoked norepinephrine release in the anterior VMH.

PMID- 11999722
TI  - Fos immunoreactivity in the diagonal band and the perinuclear zone of the
      supraoptic nucleus after hypertension and hypervolaemia in unanaesthetized rats.
AB  - We used Fos immunocytochemistry to study the effects of hypertension and
      hypervolaemia on neurones in the diagonal band of Broca and the perinuclear zone
      of the supraoptic nucleus, two nuclei that are both involved in the baroreceptor
      regulation of vasopressin neurones in the supraoptic nucleus. In addition, we
      used sino-aortic denervation to examine the role of arterial baroreceptors in the
      response to these haemodynamic changes. Sham-operated and sino-aortic denervated
      rats were infused with phenylephrine sufficient to increase blood pressure for 2
      h. Control rats were infused with the same volume of isontonic saline. Only Sham
      sino-aortic denervated rats showed reflex bradycardia in response to the
      increased blood pressure. Volume expansion was produced by infusing the rats with
      isotonic saline equal to 10% of their body weight for 10 min, which significantly
      increased central venous pressure. In the diagonal band of Broca and the
      perinuclear zone, the number of Fos-positive neurones was significantly increased
      after phenylephrine infusion. Sino-aortic denervation blocked the significant
      increase in both regions. After volume expansion, a significant increase in Fos
      staining was observed only in the perinuclear zone of the supraoptic nucleus.
      This increase was not blocked by sino-aortic denervation. Our results indicate
      that both the diagonal band of Broca and the perinuclear zone of the supraoptic
      nucleus are activated by stimulating arterial baroreceptors; however, the
      perinuclear zone of the supraoptic nucleus is stimulated during volume expansion.
      Furthermore, the activation of perinuclear zone of the supraoptic nucleus after
      volume expansion is not dependent on intact arterial baroreceptors.

PMID- 11999723
TI  - Testicular and somatic growth in Siberian hamsters depend on the melatonin-free
      interval between twice daily melatonin signals.
AB  - In Siberian hamsters, day length is encoded by the duration of the nocturnal
      melatonin signal; short and long melatonin signals over the course of several
      weeks stimulate and inhibit somatic and gonadal development, respectively, in
      prepubertal males. We sought to determine whether juvenile male Siberian hamsters
      respond to multiple melatonin signals each day and the manner in which the
      sequence of melatonin signals and the duration of the melatonin-free interval
      between signals affects development. Twenty-one day old male Siberian hamsters,
      gestated and maintained in a short-day photoperiod of 10 h light/day (10 L), were
      transferred to constant light to suppress endogenous melatonin secretion and
      received s.c. infusions of melatonin or saline for 12 days. Hamsters infused with
      saline retained small testes, whereas one short melatonin infusion each day
      resulted in significant testicular growth. Other hamsters were provided with two
      melatonin signals each day, one long (9 h) and one short (4 or 5 h); the order in
      which these signals was administered and the duration of the melatonin-free
      interval after each signal varied between groups. In asymmetrical melatonin
      infusions, the first and second daily infusions were followed by 3-h and 7-h
      melatonin-free intervals, respectively, whereas in symmetrical infusions, each
      melatonin signal was followed by a 5-h melatonin-free interval. In the
      asymmetrical sequence, the melatonin signal that immediately preceded the longer
      melatonin-free interval determined the rate gonadal growth. Equal melatonin-free
      intervals after each of the long and short daily melatonin infusions produced
      intermediate increases in gonadal and somatic development. The hypothalamic
      pituitary-gonadal axis of Siberian hamsters can respond to multiple melatonin
      signals each day, with the rate of testicular growth determined primarily by the
      duration of the melatonin-free interval following each infusion.

PMID- 11999724
TI  - Hippocampal serotonin responses in short and long attack latency mice.
AB  - Short and long attack latency mice, which are selected based on their offensive
      behaviour in a resident-intruder model, differ in their neuroendocrine regulation
      as well as in aspects of their brain serotonin system. Previous studies showed
      that the binding capacity and expression of serotonin-1A receptors in the
      hippocampal CA1 field of long attack latency mice are significantly lower than
      that found in short attack latency mice. We tested whether the functional
      responses of CA1 hippocampal cells to serotonin are also reduced in long attack
      latency mice. To this end, serotonin-induced changes in the membrane potential
      and input resistance were recorded in vitro with microelectrodes in CA1 pyramidal
      neurones of long and short attack latency mice. The data show that in long attack
      latency mice, along with a reduction of the serotonin-1A receptor mRNA
      expression, the serotonin-induced membrane hyperpolarization and decrease in
      resistance are attenuated. Basal membrane properties of CA1 neurones in the
      two.mice lines were comparable. Plasma corticosterone levels in response to a
      novelty stress were elevated in long compared to short attack latency mice and
      inversely related to the serotonin-induced responses. We tentatively conclude
      that long attack latency mice show attenuated functional responses to serotonin
      in the hippocampus, possibly linked to a chronic perturbation of hormonal levels.

PMID- 11999725
TI  - Functional consequences of morphological neuroglial changes in the magnocellular
      nuclei of the hypothalamus.
AB  - The supraoptic and paraventricular nuclei of the hypothalamus undergo reversible
      anatomical changes under conditions of intense neurohypophysial hormone
      secretion, such as lactation, parturition and chronic dehydration. This
      morphological remodelling includes a reduction in astrocytic coverage of neurones
      resulting in an increase in the number and extent of directly juxtaposed somatic
      and dendritic surfaces. There is a growing body of evidence indicating that such
      anatomical plasticity is of functional significance. Astrocytic-dependent
      clearance of electrolytes and neurotransmitters from the extracellular space
      appears to be altered under conditions where glial coverage of magnocellular
      neurones is reduced. Glutamate, for example, has been found to accumulate in the
      extracellular space in the supraoptic nucleus of lactating animals and cause a
      modulation of synaptic efficacy. On the other hand, the range of action of
      substances released from astrocytes and acting on adjacent magnocellular neurones
      is expected to be limited during such anatomical remodelling. It thus appears
      that the structural plasticity of the magnocellular nuclei does affect neuroglial
      interactions, inducing significant changes in signal transmission and processing.

PMID- 11999726
TI  - Glial-neuronal-endothelial interactions are involved in the control of GnRH
      secretion.
AB  - In recent years compelling evidence has been provided that cell-cell interactions
      involving non-neuronal cells, such as glial and endothelial cells, are important
      in regulating the secretion of GnRH, the neuropeptide that controls both sexual
      development and adult reproductive function. Modification of the anatomical
      relationship that exist between GnRH nerve endings and glial cell processes in
      the external zone of the median eminence modulates the access of GnRH nerve
      terminals to the portal vasculature during the oestrous cycle. The establishment
      of direct neuro-haemal junctions between GnRH neuroendocrine terminals and the
      portal vasculature on the day of pro-oestrus may be critical for the transfer of
      GnRH upon its release into the fenestrated capillaries of the median eminence.
      Notwithstanding the importance of these plastic rearrangements, glial and
      endothelial cells also regulate GnRH neuronal function via specific cell-cell
      signalling molecules. While endothelial cells of the median eminence use nitric
      oxide to effect this regulatory control, astrocytes employ several growth
      factors, and in particular those of the EGF family and their erbB receptors to
      facilitate GnRH release during sexual development. Loss of function of each of
      these erbB receptors involved in the astroglial control of GnRH secretion leads
      to delayed sexual development. It is clear that regulation of GnRH secretion by
      cell-cell communication mechanisms other than transsynaptic inputs is an
      important component of the central neuroendocrine process controlling mammalian
      reproduction.

PMID- 11999727
TI  - Determination of omeprazole and its metabolites in human plasma by liquid
      chromatography-mass spectrometry.
AB  - Omeprazole is a benzimidazole compound that acts as a proton-pump inhibitor.
      Because the metabolism of omeprazole is mainly catalyzed by cytochrome P-450
      (CYP) 3A4 and CYP2C19. the genetic polymorphism of CYP2C19 could be of clinical
      concern in the treatment of acid-related diseases with omeprazole. Therefore, a
      reliable method for omeprazole phenotyping is desirable in clinical situations.
      This study has demonstrated the determination of omeprazole and its metabolites
      in human plasma by liquid chromatography-three-dimensional quadrupole mass
      spectrometry with a sonic spray ionization interface. The analytical column was
      YMC-Pack Pro C18(50x2.0 mm I.D.) using acetonitrile-50 mM ammonium acetate (pH
      7.25) (1:4) at a flow-rate of 0.2 ml/min. The drift voltage was 30 V. The
      sampling aperture was heated at 110 degrees C and Shield temperature was 230
      degrees C. In the mass spectrum, the molecular ions of omeprazole,
      hydroxyomeprazole and omeprazole sulfone were clearly observed as base peaks.
      This method is sufficiently sensitive and accurate for pharmacokinetic studies of
      omeprazol.

PMID- 11999728
TI  - High-performance liquid chromatographic determination of tramadol and its O
      desmethylated metabolite in blood plasma. Application to a bioequivalence study
      in humans.
AB  - Simultaneous HPLC determination of the analgetic agent tramadol, its major
      pharmacodynamically active metabolite (O-desmethyltramadol) in human plasma is
      described. Simple methods for the preparation of the standard of the above
      mentioned tramadol metabolite and N1,N1-dimethylsulfanilamide (used as the
      internal standard) are also presented. The analytical procedure involved a simple
      liquid-liquid extraction of the analytes from the plasma under the conditions
      described previously. HPLC analysis was performed on a 250x4 mm chromatographic
      column with LiChrospher 60 RP-selectB 5-microm (Merck) and consists of an
      analytical period where the mobile phase acetonitrile-0.01 M phosphate buffer, pH
      2.8 (3:7, v/v) was used, and of a subsequent wash-out period where the plasmatic
      ballast compounds were eluted from the column using acetonitrile-ultra-high
      quality water (8:2, v/v). The whole analysis, including the equilibration
      preceding the initial analytical conditions lasted 19 min. Fluorescence detection
      (lambda(ex) 202 nm/lambda(em) 296 nm for tramadol and its metabolite, lambda(ex)
      264 nm/lambda(em) 344 nm for N1,N1-dimethylsulfanilamide) was used. The validated
      analytical method was applied to pharmacokinetic studies of tramadol in human
      volunteers.

PMID- 11999729
TI  - Indirect high-performance liquid chromatographic separation of stereoisomers of
      beta-alkyl-substituted amino acids by the application of (S)-N-(4
      nitrophenoxycarbonyl)phenylalanine methoxyethyl ester as chiral derivatizing
      agent.
AB  - The indirect high-performance liquid chromatographic enantioresolution of beta
      alkyl-substituted analogues of tyrosine, phenylalanine, 1,2,3,4
      tetrahydroisoquinoline-3-carboxylic acid and tryptophan is reported. (S)-N-(4
      Nitrophenoxycarbonyl)phenylalanine methoxyethyl ester, a recently developed
      chiral derivatizing agent, was used for pre-column derivatization of the
      investigated analytes. The diastereoisomers formed were analysed under reversed
      phase conditions. The effects of parameters such as the amount and type of the
      organic modifier and the type of the stationary phase on the resolution and
      retention of the derivatives were investigated. Chromatographic conditions were
      found for the separation of all four stereoisomers of each analyte.

PMID- 11999730
TI  - Determination of different species of homocysteine in human plasma by high
      performance liquid chromatography with ultraviolet detection.
AB  - This assay measures reduced, free oxidized, protein-bound, and total homocysteine
      in human plasma. Oxidized species of homocysteine are converted to reduced form
      by sodium borohydride, and, after precolumn derivatization with 2-chloro-1
      methylquinolinium tetrafluoroborate, homocysteine 2-S-quinolinium derivative is
      separated from those of other plasma thiol derivatives, and quantitated by ion
      paired reversed-phase high-performance liquid chromatography with ultraviolet
      detection. The reduced homocysteine sulfhydryl groups are trapped with minimal
      oxidation by derivatizing blood samples at the time of collection. With the use
      of this precise and sensitive HPLC method utilizing popular ultraviolet
      detection, homocysteine in plasma can be detected and quantitated at the level of
      0.1 and 0.2 for reduced fraction, and 0.3 and 0.5 nmol/ml for total homocysteine,
      respectively. The method is applied for determination of different fractions of
      homocysteine in plasma of apparently healthy men and women.

PMID- 11999731
TI  - Quantitative proteomics strategy involving the selection of peptides containing
      both cysteine and histidine from tryptic digests of cell lysates.
AB  - This paper describes a procedure for quantitative proteomics that selects
      peptides containing both cysteine and histidine residues from tryptic digests of
      cell lysates. Cysteine-containing peptides were selected first by covalent
      chromatography using thiol disulfide exchange. Following the release of cysteine
      containing peptides from the covalent chromatography column with reductive
      cleavage, histidine-containing peptides were captured by passage through an
      immobilized metal affinity chromatography column loaded with copper.
      Quantification was achieved in a four-step process involving (i) differential
      labeling of control and experimental samples with isotopically differing forms of
      succinic anhydride, (ii) mixing the two globally labeled samples, (iii)
      fractionating the labeled peptides by reversed-phase liquid chromatography, and
      (iv) determining the isotope ratio in individual peptides by mass spectrometry.
      The results of these studies indicate that by selecting peptides containing both
      cysteine and histidine, the complexity of protein digests could be substantially
      reduced. Up-regulated proteins from plasmid bearing Escherichia coli that had
      been induced with isopropyl beta-thiogalacto-pyranoside were identified and
      quantified by the global internal standard technology (GIST) described above.
      Database searches were greatly simplified because the number of possible peptide
      candidates was reduced more than 95%.

PMID- 11999732
TI  - Multifunctional fractionation of polyclonal antibodies by immunoaffinity high
      performance monolithic disk chromatography.
AB  - High-performance monolithic disk chromatography (HPMDC), including its affinity
      mode, is a very efficient method for fast separations of biological molecules of
      different sizes and shapes. In this paper, protein and peptide ligands,
      immobilized on the inner surface of thin, monolithic supports (Convective
      Interaction Media or CIM disks), have been used to develop methods for fast,
      quantitative affinity fractionation of pools of polyclonal antibodies from blood
      sera of rabbits, immunized with complex protein-peptide conjugates. The
      combination of several disks with different affinity functionalities in the same
      cartridge enables the separation of different antibodies to be achieved within a
      few minutes. The apparent dissociation constants of affinity complexes were
      determined by frontal analysis. Variation of elution flow rate over a broad range
      does not affect the affinity separation characteristics. Indifferent synthetic
      peptides used as biocompatible spacers do not change the affinity properties of
      the ligands. The highly reproducible results of immunoaffinity HPMDC are compared
      with data obtained by widely used enzyme-linked immunosorbent assay.

PMID- 11999733
TI  - Global internal standard technology for comparative proteomics.
AB  - The work described in this paper tests the efficacy of a global isotope labeling
      (global internal standard technology, GIST) strategy for quantification in
      proteomics. Using GIST, overexpression of beta-galactosidase in Escherichia coli
      was identified and quantified. The GIST protocol involved tryptic digestion of
      proteins from control and experimental samples followed by differential isotopic
      labeling of the resulting tryptic peptides, mixing the differentially labeled
      control and experimental digests, fractionation of the peptide mixture by
      reversed-phase chromatography, and isotope ratio analysis by mass spectrometry. N
      Acetoxysuccinimide and N-acetoxy-[2H3]succinimide were used to differentially
      derivatize primary amino groups in peptides from experimental and control
      samples, respectively. The relative concentration of isotopically labeled
      peptides was determined by isotope ratio analysis with both matrix-assisted laser
      desorption ionization mass spectrometry and tandem mass spectrometry (MS-MS).
      Peptide masses and sequences obtained by MS-MS were used to identify proteins. MS
      MS was found to be uniquely suited for isobaric peptide quantification.

PMID- 11999734
TI  - Quantitative investigation of the affinity properties of different recombinant
      forms of protein G by means of high-performance monolithic chromatography.
AB  - The recombinantly produced different forms of protein G, namely monofunctional
      immunoglobulin G (IgG) binding, monofunctional serum albumin (SA) binding and
      bifunctional IgG/SA binding proteins G, are compared with respect to their
      specific affinities to blood IgG and SA. The affinity mode of the recently
      developed high-performance monolithic disk chromatography has been used for fast
      quantitative investigations. Using single affinity disks as well as two discs
      stacked into one separation unit, one order of magnitude in adsorption capacities
      for IgG and SA were found both for monofunctional and bifunctional protein G
      forms used as specific affinity ligands. However, despite the adsorption
      difference observed, the measured dissociation constants of the affinity
      complexes seemed to be very close. The analytical procedure developed can be
      realized within a couple of minutes. Up-scaling of the developed technology was
      carried out using another type of monolithic materials, i.e. CIM affinity tubes.

PMID- 11999735
TI  - Elution behavior of unsaponifiable lipids with various capillary
      electrochromatographic stationary phases.
AB  - Capillary electrochromatographic (CEC) separations of unsaponifiable lipids,
      tocopherols (T), tocotrienols (T3), and plant sterols were studied under various
      conditions. Investigated stationary phases include pentafluorophenylsilica
      (PFPS), triacontylsilica (TCS), and octadecylsilica (ODS) phases. A baseline
      separation of four sterols (ergosterol, lanosterol, sitosterol and stigmasterol)
      on ODS was achieved and their elution order was found to be dictated by side
      chain structures. CEC of the tocol-derived compounds on PFPS in aqueous methanol
      yielded the most satisfactory results with complete resolution of all components
      eluting in the order
      deltaT3>beta3>gammaT3>epsilonP>alphaT3>deltaT>zeta2T>betaT>gammaT>alphaT, while a
      reversal in elution of the epsilonT-alphaT3 pair was observed in aqueous
      acetonitrile. CEC with a TCS phase in non-aqueous methanol led to a different
      elution pattern
      deltaT3>gammaT3>betaT3>alphaT3epsilonT>deltaT>(zeta2+gamma)T>betaT>alphaT,
      despite favorable resolution of the (gamma-zeta2)T pair along with the
      observation of inseparable(beta-gamma)T and (beta-gamma)T3 pairs in non-aqueous
      dimethylformamide. Non-aqueous acetonitrile mobile phases provided unique
      selectivity for the (gamma-zeta2)T pair and isomer separations on TCS. Variations
      in separation and retention factors of relevant antioxidant species with CEC
      variables were evaluated. Examples of CEC quantification of unsaponifiable
      fractions of rice bran oils and soybean oils are presented.

PMID- 11999736
TI  - Phosphatidylcholine isolation from egg yolk phospholipids by high-performance
      liquid chromatography.
AB  - Cell membrane components have been increasingly recognized as important
      biochemicals in the fields of biochemistry and pharmacy due to their relationship
      with metabolite transport in the cells. Among the components, phosphatidylcholine
      (PC) is considered a valuable biochemical, because it is difficult to
      commercialize. PC demand has been largely increased in the fields of the
      nutrient, cosmetic and pharmacy industries, and so the development of a
      preparative chromatography process is critical to supply a low-cost PC. In this
      study, we investigated the HPLC separation of phospholipid originated from egg
      yolk, which contains 80% (w/w) PC and 15% (w/w) phosphatidylethanolamine. Column
      temperature, mobile phase composition and its flow-rate and kinds of stationary
      phase were varied to understand the effectiveness of PC separation. For studying
      the relationship between recovery yield and sample loading amount in HPLC, we
      performed overloading experiments. In this way, we successfully separated PC with
      over 99% purity and with 98% yield with the following HPLC operating conditions;
      pure methanol as a mobile phase, 2.0 ml/min flow-rate and 1000 mg/ml feed
      concentration in a KR-100-10SIL column.

PMID- 11999737
TI  - Fractionation of soybean phospholipids by preparative high-performance liquid
      chromatography with sorbents of various particle size.
AB  - Normal-phase high-performance liquid chromatography was used on a preparative
      scale to seperate phosphatidylethanolamine (PE), phosphatidylinositol (PI) and
      phosphatidylcholine (PC) phospholipids from soybean. Separation was achieved
      using mixtures of three solvents, hexane, methanol and isopropanol. The optimized
      mobile phase compositions were experimentally determined while operating in a
      linear gradient mode using 15, 5-20, 25-40, and 40-63 microm preparative
      particles as well as 4 microm analytical particles. A gradient mobile phase was
      established on a commmercially available analytical Nova-Pak column such that
      hexane linearly decreased from 85 to 0 as isopropanol and methanol linearly
      increased in two gradient steps from 10 to 30 and 5 to 70 respectively. The total
      run time was 25 min at a flow-rate of 1.5 ml/min. A slight change in mobile phase
      composition was required to increase the resolution of phospholipids. The 15
      microm particle size gave the best separation of the preparative particle sizes
      examined based on their resolutions between PE and PI and PI and PC. Finally, the
      retention factors of PE and PC were correlated in terms of mobile phase
      composition.

PMID- 11999738
TI  - Separation, identification and quantitation of ceramides in human cancer cells by
      liquid chromatography-electrospray ionization tandem mass spectrometry.
AB  - Ceramides are important intracellular second messengers that play a role in the
      regulation of cell growth, differentiation and programmed cell death. Qualitative
      and quantitative analysis of these second messengers requires sensitive and
      specific analytical methods to detect endogenous levels of individual ceramide
      species and to differentiate between them. Nine synthetic ceramides were
      separated by liquid chromatography coupled to tandem mass spectrometry on a C18
      bonded silica column. The lipids were eluted in gradient elution mode using a
      mixture of water, acetonitrile and 2-propanol as mobile phase. They were detected
      by reaction monitoring performed on positive ion electrospray generated ions.
      Collision-induced fragmentations conducted on ceramides produced a well
      characteristic product ion at m/z 264, making multiple reaction monitoring (MRM)
      well suited for various ceramides quantitative measurements. After optimization
      of the extraction step, the proposed methodology was able to identify and
      quantify different ceramide species issued from human cancer cells. The method
      could be validated for C16, C18 and C20 ceramides, quantified at the nanogram
      level. The validation exhibits good results with respect to linearity, accuracy
      and precision.

PMID- 11999739
TI  - Determination of reboxetine, a recent antidepressant drug, in human plasma by
      means of two high-performance liquid chromatography methods.
AB  - Reboxetine is a new norepinephrine reuptake inhibitor (NRI) drug recently
      introduced in the therapy for depressed patients. It is effective in the
      treatment of severe depression and safer to use than traditional tricyclic
      antidepressants. In this paper an original high-performance liquid chromatography
      (HPLC) method with ultraviolet detection for the determination of reboxetine in
      human plasma is described. It uses a C8 reversed-phase column and a mobile phase
      composed of acetonitrile and aqueous tetramethylammonium perchlorate. For the
      analysis of plasma samples containing very low levels of reboxetine, another HPLC
      method with fluorimetric detection was developed (limit of quantitation, LOQ=11
      ng ml(-1); limit of detection, LOD=4 ng ml(-1)). The fluorimetric method is based
      on precolumn derivatisation of reboxetine with 9-fluorenylmethyl chloroformate.
      An accurate sample pretreatment of human plasma samples has been implemented by
      means of solid-phase extraction (SPE) on Oasis HLB (hydrophilic-lipophilic
      balance) cartridges with very high extraction yields (>95%). Both methods were
      applied to the analysis of plasma samples from depressed patients undergoing
      therapy with reboxetine and gave satisfactory results in terms of precision
      (RSD<4.5%) and accuracy (mean recovery>94%).

PMID- 11999740
TI  - Behavior and characteristics of amine derivatives obtained with o
      phthaldialdehyde/3-mercaptopropionic acid and with o-phthaldialdehyde/N-acetyl-L
      cysteine reagents.
AB  - A comprehensive evaluation of papers dealing with the HPLC quantitation of amines
      as o-phthaldialdehyde (OPA) derivatives has been given and discussed in details.
      The stability and characteristics of selected representatives of mono [methyl-,
      ethyl-, n-/isopropyl, n-/isobutyl-, tert.-butyl-, sec.-butyl-, isoamyl amines and
      ethanolamine), di- and polyamines (ethylenediamine, 1,2-propylenediamine, 1,3
      propylenediamine, agmatine, tyramine, putrescine, cadaverine, histamine,
      spermine, spermidine, and bis(hexamethylene)triamine] have been investigated as
      their OPA/3-mercaptopropionic acid (MPA) and OPA/N-acetyl-L-cysteine (NAC)
      derivatives, from an analytical point of view, performing photodiode array and
      fluorescence detection, simultaneously. All amines having in their original
      structure the NH2-CH2-R moiety, in accord with the amino acids of the same
      structure, furnished more than one OPA derivative: their initially formed species
      transformed to further ones. On the basis of on-line HPLC-MS the transformed
      derivatives were proved to be the corresponding isoindoles that contain an
      additional OPA molecule. In order to achieve optimum analytical conditions
      derivatization reagents have been applied in different composition, in parallel.
      The OPA and the SH-group additive contents of the reagents have been varied in
      the mole ratios of OPA/MPA(NAC)=1:3 and OPA/MPA(NAC)=1:50. Data obtained proved
      that performing derivatizations by means of the OPA/MPA(NAC)=1:50 reagents
      resulted in two benefits: both the stability of derivatives could have been
      increased and the number of the transformed derivatives decreased. In case of
      aliphatic amines and in ethanolamine, the transformation of the initially formed
      derivative can be either quantitatively avoided as in the case of ethanolamine,
      or considerably decreased, below 1%, as in the cases of the other aliphatic
      monoamines investigated. As to the behavior of di- and polyamines the stability
      of derivatives has been considerably improved, the number of species have been
      decreased from four to two with the exception of spermidine. Stability values
      characterized both by the UV and fluorescence responses, as a function of the
      reaction time (from 90 s up to 6 h) have been given in details.

PMID- 11999741
TI  - Simultaneous determination of N-oxides and free bases of pyrrolizidine alkaloids
      by cation-exchange solid-phase extraction and ion-pair high-performance liquid
      chromatography.
AB  - Cation-exchange solid-phase extraction using LiChrolut SCX (Merck, Darmstadt)
      cartridges filled with polymeric strong cation-exchanger enabled efficient
      isolation of both N-oxides and free bases of pyrrolizidine alkaloids (PAs). The
      recoveries were about 80% for retrorsine-N-oxide, 90% for retrorsine and 100% for
      senkirkine and were assessed both by TLC-densitometry and ion-pair high
      performance liquid chromatography (HPIPC) on Hypersil BDS C8 stationary phase and
      hexane-l-sulfonic acid as ion-pairing agent. The applied HPIPC gradient procedure
      was suitable for separation of PAs with various types of structures (N-oxides,
      free bases, otonecine-PAs). The method limits of detection and quantitation,
      respectively, ranged from 0.06 ng/microl (senecionine) and 0.2 ng/microl
      (senkirkine) to 0.1 and 0.35 ng/microl for retrorsine-N-oxide. For each component
      calibrated by linear regression method, correlation coefficients were higher than
      0.9995 (six-point calibration from 4 to 100 microg/ml). The elaborated procedure
      was used in searching for PAs in plant derived samples from Symphytum sp.
      (comfrey), Petasites hybridus and Petasites albus (butterbur), Tussilago farfara
      (coltsfoot), Emilia coccinea (tassel flower) and Doronicum columnae (leopard's
      bane). For the last three samples macrocyclic PAs (senecionine, senecionine-N
      oxide. senkirkine) have been detected for the first time. Details of precision of
      the analyses are also included.

PMID- 11999742
TI  - Monitoring of azo dye degradation processes in a bioreactor by on-line high
      performance liquid chromatography.
AB  - A technical solution and development of a method for on-line HPLC monitoring of
      bioreactor processes in a membrane reactor system are presented. Experiences in
      system design for the continuous coupling of a bioreactor system with capillary
      by-pass circuits using membrane flow cells and a dual HPLC system are reported. A
      continuously working integrated sample purification step by ultrafiltration with
      the membrane cell coupling is established. Using electrical switching valves and
      separated pumping and eluent systems, the dual HPLC system allows diode array
      detection as well as measurement of the refractive index. The application of the
      on-line HPLC monitoring system is demonstrated by measuring the anaerobic H-acid
      degradation kinetics. H-acid, 1-amino-8-hydroxynaphthalene-3,6-disulfonic acid,
      is one of the most important coupling components for a variety of direct,
      mordant, reactive dyes which remains in the process water and the textile dyeing
      effluents in high concentration.

PMID- 11999743
TI  - Effect of reduced glutathione on the stability of pigments in paprika powders
      studied by multiwavelength spectrometry and high-performance liquid
      chromatography.
AB  - Multiwavelength spectrometry and reversed-phase high-performance liquid
      chromatography have been employed for the study of the effect of reduced
      glutathione and storage time on the pigments of paprika powders. The evaluation
      of the data by principal component analysis and cluster analysis proved that the
      storage time exerts the highest effect of the decomposition rate of pigments. The
      stability of some pigment fractions was modified in the presence of reduced
      glutathione. However, the effect was of secondary importance. Multiwavelength
      spectrometry combined with HPLC can be successfully used for the study of the
      stability of pigments of paprika powder.

PMID- 11999744
TI  - Effect of particle size in preparative reversed-phase high-performance liquid
      chromatography on the isolation of epigallocatechin gallate from Korean green
      tea.
AB  - To isolate epigallocatechin gallate (EGCG) of catechin compounds from Korean
      green tea (Bosung, Chonnam), a C18 reversed-phase preparative column (250x22 mm)
      packed with packings of three different sizes (15, 40-63, and 150 microm) was
      used. The sample extracted with water was partitioned with chloroform and ethyl
      acetate to remove the impurities including caffeine. The mobile phases in this
      experiment were composed of 0.1% acetic acid in water, acetonitrile, methanol and
      ethyl acetate. The injection volume was fixed at 400 microl and the flow rate was
      increased as the particle size becomes larger. The isolation of EGCG with
      particle size was compared at a preparative scale and the feasibility of
      separation of EGCG at larger particle sizes was confirmed. The optimum mobile
      phase composition for separating EGCG was experimentally obtained at the particle
      sizes of 15 and 40-63 microm in the isocratic mode, but EGCG was not purely
      separated at the particle size of 150 microm.

PMID- 11999745
TI  - Suppressed ion chromatography for monitoring chemical impurities in steam for
      geothermal power plants.
AB  - A suppressed ion chromatography (IC) technique has been evaluated as a chemical
      monitoring tool for detecting major anions (F-, Cl-, NO3- and SO4(2-)) of
      condensed steam in geothermal power plants. It is shown that the suppressed IC
      technique provides a suitable means for preventing possible damage to generating
      equipment in the geothermal industry. An electrical conductivity detector (0.1
      microS sensitivity) with an anion-exchange column (IonPac AS4A-SC), a micro
      membrane suppressor (AMMS II), and an isocratic high-pressure pump system were
      successfully used for detecting low concentrations of inorganic anions. Method
      detection limits for the anions of interest were <0.184 mg/L. Details of the IC
      methodology as well as some experimental results obtained during its application
      for the chemical monitoring of geothermal steam pipes are also described.

PMID- 11999746
TI  - Determination of polycyclic aromatic hydrocarbons in seawater by high-performance
      liquid chromatography with fluorescence detection following micelle-mediated
      preconcentration.
AB  - In this work, the nonionic surfactant polyoxyethylene-10-lauryl ether has been
      used for the extraction and preconcentration of 14 polycyclic aromatic
      hydrocarbons, classified as priority pollutants by the US Environmental
      Protection Agency, from seawater samples. The cloud-point preconcentration
      previous separation by HPLC and quantification using fluorimetric detection and
      wavelength programming allow to determine these pollutants with detection limits
      ranging from 1.0 to 1.5 x 10(2) ng/l with RSDs better than 10.4%. The methodology
      is evaluated using well-established extraction and preconcentration methods and
      GC-MS.

PMID- 11999747
TI  - Separation of polycyclic aromatic hydrocarbons with sodium
      dodecylbenzenesulfonate in electrokinetic chromatography.
AB  - Sodium dodecylbenzenesulfonate (SDBS) was used as an additive in separating a
      broad range of polycyclic aromatic hydrocarbons (PAHs) by capillary
      electrophoresis. In the absence of micelles, using an acetonitrile-water (40:60)
      electrolyte, the separation mechanism was predicted as solvophobic association of
      the PAH molecules with hydrophobic chains of the SDBS surfactant and a possible
      pi-pi interaction between aromatic groups of PAHs and SDBS. The effects of
      voltage, acetonitrile and SDBS concentrations on separation were investigated.
      SDBS provides a good selectivity for PAHs not only between different ring numbers
      (1 to 5) but also between the pairs of structural isomers. Under optimum
      conditions, 11 aromatic compounds were separated with efficiencies between
      130,000 and 230,000 theoretical plates. Reproducibilities of migration times
      range between 1.15 and 1.55% RSD and peak areas between 2 and 9% RSD.

PMID- 11999748
TI  - Analysis of linear and cyclic oligomers in polyamide-6 without sample preparation
      by liquid chromatography using the sandwich injection method. III. Separation
      mechanism and gradient optimization.
AB  - The first six linear and cyclic oligomers of polyamide-6 can be quantitatively
      determined in the polymer using HPLC with the sandwich injection method and an
      aqueous acetonitrile gradient. In this final part of the triptych concerning the
      determination of the oligomers in polyamide-6, the irregular elution behavior of
      the cyclic monomer compared to the cyclic oligomers was investigated. We also
      optimized the separation of the involved polyamide oligomers, with respect to
      gradient steepness, stationary phase, column temperature and mobile phase pH. The
      irregular elution behavior of the cyclic monomer could be caused by its
      relatively large exposed/accessible hydrophobic surface, which permits relatively
      easy penetration into the hydrophobic stationary phase giving extra retention.
      The dipole moment of the different oligomers was used as a measure for this
      exposed/accessible hydrophobic area to correlate the retention factors using
      quantitative structure-retention relationships. We also studied the retention
      behavior of the polyamide, which is injected each run directly onto the column
      and modifies the stationary phase. Using a 250-microl post gradient injection
      zone of formic acid on a 250x3 mm Zorbax SB-C18 column, the polyamide could be
      effectively removed from the stationary phase after each separation. The linear
      solvent strength (LSS) model was used to optimize the separation of the first six
      linear and cyclic oligomers. As the LSS model assumes a linear correlation
      between the modifier concentration and the logarithm of the retention factor and
      the cyclic monomer and dimer show extreme curvation of this relation in the
      eluting region, we investigated different models to predict gradient elution from
      isocratic data. A direct translation of the isocratic data to gradient retention
      times did not yield adequate retention times using the LSS model. It was found
      that the LSS model worked acceptably if gradient retention times were used as
      input data. Even for fast non-linearly eluting components, an average error of
      0.4 resolution units of 4sigma was obtained. Using the LSS model in combination
      with different column temperatures and mobile phase pH values, a separation of
      the first six linear and cyclic oligomers was accomplished.

PMID- 11999749
TI  - Quantitation of functionality of poly(methyl methacrylate) by liquid
      chromatography under critical conditions followed by evaporative light-scattering
      detection. Comparison with NMR and titration.
AB  - Atom transfer radical polymerisation (ATRP) is a versatile 'living' controlled
      polymerisation technique for the synthesis of well-defined architectures such as
      block copolymers, gradient copolymers, hyperbranched polymers and telechelic
      polymers. ATRP provides control over molecular mass and molecular mass
      distribution and is suitable for the polymerisation of a wide variety of
      monomers, including methyl methacrylate. A chromatographic method was developed
      for an endgroup-based separation of low-molecular-mass poly(methyl methacrylate)
      (PMMA), based on liquid chromatography under critical conditions. With this
      method the PMMA, irrespective of its low-molecular-mass, is separated according
      to endgroups (functionality) due to interactions of the polar endgroups with the
      non-modified silica based stationary phase. The different series were identified
      using on-line atmospheric pressure ionisation electrospray mass spectrometry and
      quantified by evaporative light scattering detection. These results were compared
      with those obtained by NMR and titration.

PMID- 11999750
TI  - Endgroup-based separation and quantitation of polyamide-6,6 by means of critical
      chromatography.
AB  - Polyamide-6,6 is a polycondensation product from the two monomers adipic acid and
      1,6-hexamethylenediamine. Depending on the reacted amount of these monomers,
      different ratios of amine and carboxylic acid endgroups can be formed. Besides
      linear chains, cyclic polyamides will also be formed. Using critical
      chromatography, polyamide-6,6 can be separated independently of molar mass.
      Retention is based solely on endgroup functionality. It is demonstrated that high
      molecular-mass polyamide-6,6 (Mw approximately 20,000-30,000) can be separated
      using this approach. The separation was optimized by using different parameters,
      such as percentage modifier, temperature and pressure. The concentration of
      phosphoric acid was used for selective retention of the different endgroup
      functionalities. Using this property, a new method called critical gradient
      chromatography was performed where the mobile phase changes from a weak to a
      strong solvent with respect to the endgroup functionality, while retaining the
      critical conditions of the backbone unit. Quantification using UV detection is
      discussed.

PMID- 11999751
TI  - Determination and pharmacokinetic profile of omeprazole in rat blood, brain and
      bile by microdialysis and high-performance liquid chromatography.
AB  - The disposition and biliary excretion of omeprazole was investigated following
      i.v. administration to rats at 10 mg/kg. We used a microdialysis technique
      coupled to a validated microbore HPLC system to monitor the levels of protein
      unbound omeprazole in rat blood, brain and bile, constructing the relationship of
      the time course of the presence of omeprazole. Microdialysis probes were
      simultaneously inserted into the jugular vein toward right atrium, the brain
      striatum and the bile duct of the male Sprague-Dawley rats for biological fluid
      sampling after the administration of omeprazole (10 mg/kg) through the femoral
      vein. The concentration-response relationship from the present method indicated
      linearity (r2>0.995) over a concentration range of 0.01-50 microg/ml for
      omeprazole. Intra-assay and inter-assay precision and accuracy of omeprazole fell
      well within the predefined limits of acceptability. Following omeprazole
      administration, the blood-to-brain coefficient of distribution was 0.15, which
      was calculated as the area under the concentration versus time curve (AUC) in the
      brain divided by the AUC in blood (k=AUCbrain/AUCblood). The blood-to-bile
      coefficient of distribution (k=AUCbile/AUCblood) was 0.58. The decline of unbound
      omeprazole in the brain striatum, blood and bile fluid suggests that there was
      rapid exchange and equilibration between the compartments of the peripheral and
      central nervous systems. In addition, the results indicated that omeprazole was
      able to penetrate the blood-brain barrier and undergo hepatobiliary excretion.

PMID- 11999752
TI  - Application of capillary zone electrophoresis to the separation and
      characterization of poly(amidoamine) dendrimers with an ethylenediamine core.
AB  - Generations 0 through 5 of ethylenediamine-core poly(amidoamine) dendrimers were
      synthesized and capillary zone electrophoresis has been applied to the separation
      of different generations of synthesized dendrimers and for the characterization
      of individual generations.

PMID- 11999753
TI  - Analysis of thiabendazole and procymidone in fruits and vegetables by capillary
      electrophoresis-electrospray mass spectrometry.
AB  - A capillary electrophoresis-mass spectrometry method for determining procymidone
      and thiabendazole in apples, grapes, oranges, pears, strawberries and tomatoes is
      described. Separation is achieved using a buffer of formic acid-ammonium formate
      at pH 3.5 with 2% of methanol. Fungicide residues present in the sample are
      preconcentrated by both solid-phase extraction and injection of large sample
      volumes into the capillary by a stacking technique, to obtain lower detection
      limits. Ionization is performed at atmospheric pressure in an electrospray type
      source and detection is carried out using positive ionization and selected ion
      monitoring modes. The quantitation limits are 0.005 and 0.05 mg kg(-1), and the
      mean recoveries are 64 and 75% for thiabendazole and procymidone, respectively,
      with relative standard deviations below 12% (n=5). Real fruit and vegetable
      samples are analyzed by the proposed method showing that residues of both
      fungicides are frequently present.

PMID- 11999754
TI  - Capillary electrophoresis for the determination of new markers of natural latex
      quality.
AB  - Nowadays, increasing use of latex products in the healthcare area has also led to
      an increase in new scientific controls of raw material and manufactured products
      in order to maintain higher standards in quality control. Since field latex is a
      rich environment for microbial growth, in the absence of adequate preservation,
      the carbohydrates that it contains become microbiologically oxidised to the so
      called volatile fatty acids (VFAs). Samples of natural rubber latex coming from
      different countries and processed in different ways have been tested by applying
      a capillary electrophoresis method for the measurement of the short-chain organic
      acids present in sera. The separation was performed with phosphate buffer at pH
      6.25 and cetyltrimethylammonium bromide (CTAB) as background electrolyte in an
      uncoated fused-silica capillary with -10 kV of applied potential. The sample
      needs no other pre-treatment more than coagulation to obtain the serum. In the
      assayed samples, it has been shown that poorly-preserved latex presented higher
      amounts of succinic acid and lower amounts of malic acid. The succinic to malic
      acid ratio may be an important parameter because it cannot be altered by dilution
      or similar processes such as the traditional VFA index, used to determine the
      quality of latex. Ratios for succinic to malic acid <0.6 have been found for well
      preserved latex and >0.6 for poorly-preserved latex.

PMID- 11999755
TI  - Simple high-performance liquid chromatography method for the simultaneous
      determination of ketoconazole and piperine in rat plasma and hepatocyte culture.
AB  - Piperine, a major alkaloid of black and long peppers has been reported to act as
      bioavailability enhancer of several drugs by inhibiting drug metabolising enzymes
      and/or by increasing oral absorption. Ketoconazole is a well established potent
      inhibitor of CYP 3A4 and P-glycoprotein. A simple and rapid HPLC method has been
      developed for the simultaneous analysis of ketoconazole and piperine in rat
      plasma and hepatocyte culture. Analysis was performed using a Symmetry C18 column
      (150x4.6 mm, 5 microm) and isocratic elution with 25 mM KH2PO4 (pH 4.5)
      acetonitrile (50:50) with a flow-rate of 1 ml/min. Photodiode array detection was
      used to simultaneously monitor piperine at 340 nm and ketoconazole at 231 nm in a
      single sample. Calibration plots in spiked plasma, hepatocytes and William's
      medium E were linear over the range studied (10-2000 ng for both drugs). The
      detection limits for piperine and ketoconazole are 2 and 4 ng, respectively, and
      the limits of quantitation are 10 and 12 ng, respectively. Intra- and inter-assay
      variations were less than 8%.

PMID- 11999756
TI  - Fast screening method for the determination of angiotensin II receptor
      antagonists in human plasma by high-performance liquid chromatography with
      fluorimetric detection.
AB  - A selective, accurate and precise high-performance liquid chromatographic assay
      coupled to fluorescence detection was developed for the detection of some
      angiotensin II receptor antagonists (ARA II): Losartan, Irbesartan, Valsartan,
      Candesartan cilexetil and its metabolite Candesartan MI. The analytes and the
      internal standard (bumetanide, a high-ceiling diuretic) were extracted from
      plasma under acidic conditions by means of solid-phase extraction using C8
      cartridges. This procedure allowed recoveries close to 80% for all these drugs
      excluding Candesartan cilexetil (70%) which presented adsorption processes on
      glass and plastic walls. The analytes and potential interferences were separated
      on a reversed-phase column, muBondapak C18, at room temperature. A gradient
      elution mode was used to carry out the separation, the optimal mobile phase being
      composed of acetonitrile-5 mM acetate buffer, pH 4, at variable flow-rates (from
      1.0 to 1.2 ml/min). Fluorescence detector was set at an excitation wavelength of
      250 nm and an emission wavelength of 375 nm. Intra- and inter-day relative
      standard deviations for all the compounds were lower than 8% except for Losartan
      (12%) and the method assesses a quite good accuracy (percentage of relative error
      approximately 6% in most of the cases). The limit of quantitation for these
      compounds was 3 ng/ml for Candesartan cilexetil and M1, 16 ng/ml for Losartan and
      50 ng/ml for Irbesartan and Valsartan, which allows their determination at
      expected plasma concentration levels. This assay method has been successfully
      applied to plasma samples obtained from hypertensive patients under clinical
      studies after oral administration of a therapeutic dose of some of these ARA II
      compounds.

PMID- 11999757
TI  - Validation of a high-performance liquid chromatography method for the
      determination of pancuronium in Pavulon injections.
AB  - A new high-performance liquid chromatography (HPLC) method was developed for the
      quality control of pancuronium bromide and its degradation products. The HPLC
      method used a 5-microm Supelcogel ODP-50 (150x4 cm) column with acetonitrile
      CH3OH-water-F3CCOOH (20.5:74.9:0.1, v/v) as the mobile phase (pH value 2.0
      adjusted with trifluoroacetic acid) at a flow-rate 0.8 ml/min and UV detection at
      210 nm. The Beer's law plots were found to be linear over the concentration range
      0.4-1.2 mg/ml of pancuronium bromide and 0.04-0.08 mg/ml of desacetyl degradation
      products (R2=0.9995). The RSD of the peak areas was 1.09% and the recovery was
      102.43%. The RSD value shows good precision, acceptable accuracy and
      reproducibility of the new method for the determination of pancuronium bromide in
      presence of its desacetyl degradation products. The method is rapid and sensitive
      enough to be used for Pavulon injection analysis.

PMID- 11999758
TI  - Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the
      quantitation of domperidone in human plasma.
AB  - A rapid and sensitive method for the determination of domperidone in plasma was
      developed, using high-performance liquid chromatographic separation with tandem
      mass spectrometry detection. The samples were rendered basic with 1 M Na2CO3 and
      the domperidone extracted using tert.-butyl methyl ether, followed by back
      extraction into formic acid (2% in water). Chromatography was performed on a
      Phenomenex Luna C8 (2), 5 microm, 150x2 mm column with a mobile phase consisting
      of acetonitrile-0.02% formic acid (300:700, v/v), delivered at 0.2 ml/min.
      Detection was performed using an Applied Biosystems Sciex API 2000 mass
      spectrometer set at unit resolution in the multiple reaction monitoring mode.
      TurbolonSpray ionisation was used for ion production. The mean recovery of
      domperidone was +/- 100%, with a lower limit of quantification set at 0.189
      ng/ml. This assay method makes use of the increased sensitivity and selectivity
      of tandem mass spectrometric detection resulting in a rapid (extraction and
      chromatography) and sensitive method for the determination of domperidone in
      human plasma, which is more sensitive than previously described methods.

PMID- 11999759
TI  - Highly specific and sensitive liquid chromatography-tandem mass spectrometry
      method for the determination of 3-desmethylthiocolchicine in human plasma as
      analyte for the assessment of bioequivalence after oral administration of
      thiocolchicoside.
AB  - A sensitive method for the determination of 3-desmethylthiocolchicine in plasma
      was developed, using high-performance liquid chromatographic separation with
      tandem mass spectrometric detection. The plasma samples were extracted with ethyl
      acetate and separated on a Phenomenex Luna C18(2) 5 microm, 150x2 mm column with
      a mobile phase consisting of acetonitrile-0.005% formic acid (350:650, v/v) at a
      flow rate of 0.35 ml/min. Detection was achieved by an Applied Biosystems API
      2000 mass spectrometer (LC-MS-MS) set at unit resolution in the multiple reaction
      monitoring mode. TurbolonSpray ionisation was used for ion production. The mean
      recovery for 3-desmethylthiocolchicine was 70%, with a lower limit of
      quantification set at 0.39 ng/ml. The increased selectivity of mass spectrometric
      (MS-MS) detection allowed us to distinguish between thiocolchicoside and its
      primary metabolite 3-desmethylthiocolchicine in human plasma, thereby giving more
      insight about the pharmacokinetics of the drug in humans.

PMID- 11999760
TI  - High-performance liquid chromatographic method for the assay of dexamethasone and
      xylometazoline in nasal drops containing methyl p-hydroxybenzoate.
AB  - A rapid and sensitive high-performance liquid chromatographic method has been
      developed for the determination of dexamethasone sodium phosphate (DSP),
      xylometazoline hydrochloride (XMC) and methyl p-hydroxybenzoate (MHB). An assay
      of the compounds has been performed on a HPLC system GBC 1210, at controlled room
      temperature, on a Nucleosil C8 column (250x3 mm, 5 microm). The mobile phase was
      acetonitrile-water (35:65, v/v), at a flow-rate of 1 ml min(-1). The parameters
      for validation such as linearity (r>0.9996), precision (RSD: 0.51-(1.93%), limit
      of detection and quantification (2.032 x 10(-4) and 4.063 x 10(-4) mg ml(-1) for
      DSP, 9.7 x 10(-5) and 1.953 x 10(-4) mg ml(-1) for XMC, 1.953 x 10(-4) and 3.096
      x 10(-4) mg ml(-1) for MHB) have also been reported. The method was applied to
      the determination of DSP, XMC and MHB in nasal drops. The statistical parameters
      were found to be satisfactory, with recovery values ranging from 98.69 to 101.60%
      (RSD: 0.32-1.03%). The method is simple and accurate and therefore suitable for
      the simultaneous determination of these compounds in dosage form.

PMID- 11999761
TI  - Improved procedure for the the determination of rofecoxib in human plasma
      involving 96-well solid-phase extraction and fluorescence detection.
AB  - An improved assay for the determination of rofecoxib in human plasma samples is
      described. The analyte and an internal standard were extracted from the plasma
      matrix using solid-phase extraction in the 96-well format with an Empore C8-SD
      extraction plate. The analytes are chromatographed on a Waters Symmetry C18
      analytical column (3.5 microm, 50x4.6 mm) with a mobile phase consisting of
      acetonitrile-water (35:65, v/v). Analyte detection was via fluorescence following
      post-column photochemical derivatization. Eight point calibration curves over the
      concentration range of 0.5-80 ng/ml yielded a linear response when a 1/y weighted
      linear regression model was employed. Based on the replicate analyses (n=5) of
      spiked standards, the within-day assay precision was better than 8% RSD at all
      points on the calibration curve, within-day accuracy was within 6% of nominal at
      all standard concentrations. The between-run precision and accuracy of the assay,
      as calculated from the results of the analysis of quality control samples, was
      better than 7% RSD and within 5% of nominal. Assay throughput was improved by a
      factor of three as compared to previously described methods. The method was
      partially automated using a combination of a Packard Multi-Probe liquid handling
      system and a TomTec Quadra 96 workstation.

PMID- 11999762
TI  - Quantitative determination of oxprenolol and timolol in urine by capillary zone
      electrophoresis.
AB  - A simple capillary zone electrophoretic method with UV detection has been
      developed for the quantitative determination of the beta-adrenoreceptor
      antagonists (beta-blockers) oxprenolol and timolol in human urine, preceded by a
      solid-phase extraction step. The electrophoretic separation was performed on a 78
      cm x 75 microm I.D. fused-silica capillary (effective capillary length: 70 cm).
      The electrolyte consisted of a Na2B4O7-H3BO3 (50 mM), pH 9. The introduction of
      the sample was made hydrostatically for 20 s and the running voltage 25 kV at the
      injector end of the capillary. Photometric detection was used at a wavelength of
      229 nm for oxprenolol and 280 nm for timolol. Under these conditions oxprenolol
      migrated at 4.76+/-0.05 min and timolol at 4.97+/-0.05 min. The solid-phase
      extraction methods were optimised for each beta-blocker and provided recoveries
      of 72.8% for timolol and 94.52% for oxprenolol. Good resolution from the
      endogenous compounds present in the urine matrix were achieved for both
      compounds. The method was applied to the determination of both beta-blockers in
      pharmaceutical formulations and urine samples obtained from hypertensive patients
      after the ingestion of a therapeutic dose (in a 24-h time interval after the
      ingestion). The quantitative results were compared with results previously
      obtained at our laboratories by HPLC and were found to be in good agreement. Good
      reproducibility, linearity, accuracy and quantitation limits (in urine) of 0.19
      microg/ml for timolol and 0.20 microg/ml for oxprenolol were obtained, allowing
      the method to be applied to pharmacokinetic studies of these compounds.

PMID- 11999763
TI  - Advances in the evaluation of the stability and characteristics of the amino acid
      and amine derivatives obtained with the o-phthaldialdehyde/3-mercaptopropionic
      acid and o-phthaldialdehyde/N-acetyl-L-cysteine reagents. High-performance liquid
      chromatography-mass spectrometry study.
AB  - The composition of the amino acid and amine derivatives obtained with the o
      phthaldialdehyde (OPA)/3-mercaptopropionic acid (MPA) and with the OPA/N-acetyl-L
      cysteine (NAC) reagents was investigated by on-line HPLC-electrospray ionization
      MS. The initially formed derivatives proved to be, as expected, the corresponding
      isoindoles while their transformed species contained one additional OPA molecule.
      Based on the MS spectra of all transformed OPA derivatives a reaction pathway is
      suggested. This reaction mechanism was supported both by the molecular ions of
      the endproducts and by the presence of several selective fragment ions that
      served as an explanation to the structure of the believed to be less stable OPA
      derivatives. It has been shown that more than one OPA derivative forms in all
      those cases when the compound to be derivatized does contain the NH2-CH2-R
      moiety. Thus, amino acids like e.g. glycine, histidine, beta-alanine, gamma
      aminobutyric acid, epsilon-aminocaproic acid, ornithine, and also several
      aliphatic mono- and diamines provide more than one OPA derivative. Analytical
      consequences of this experience were utilized by altering the reagent's
      composition. Reagents containing mole ratios of [OPA]/[MPA] or [OPA]/[NAC]=1/50
      resulted in two benefits, simultaneously: (i) in a decrease of the transformation
      rate of the initially formed derivative, and, (ii) in an increase of the overall
      stability of the total of derivatives.

PMID- 11999764
TI  - Butanol extraction to predict bioavailability of PAHs in soil.
AB  - The feasibility of a mild-solvent extraction procedure to predict the
      bioavailability of individual polycyclic aromatic hydrocarbons (PAHs) in soil was
      assessed. The quantities that were degraded during the course of biodegradation
      of phenanthrene and pyrene in soil with or without plants correlated with the
      amounts extracted by n-butanol, with R2 values of 0.971 and 0.994, respectively.
      Six consecutive groups of earthworms removed ca. 70% of the pyrene remaining
      after extensive biodegradation, a value similar to the quantity extracted by n
      butanol. The amount of chrysene aged in sterilized soil that was extracted by n
      butanol was not statistically different from the quantities assimilated by earth
      worms (Eisenia fetida) introduced into the soil. Such a mild extraction procedure
      may be useful as a means of predicting PAH bioavailability.

PMID- 11999765
TI  - The effect of chloroquine, quinacrine, and metronidazole on both soybean plants
      and soil microbiota.
AB  - Chloroquine, quinacrine, and metronidazole are used extensively for therapeutic
      purposes. Substantial quantities of these compounds end up in the environment.
      The potential effect of these compounds on soybean and on the protozoa in soil
      was assessed. The growth of soybean plants was affected by increasing
      concentrations of the chloroquine, metronidazole, and quinacrine dihydrochloride.
      The plants were particularly sensitive to low concentrations of metronidazole.
      The number of bacteria and protozoa in soil was either unchanged or increased in
      the presence of chloroquine and quinacrine. However, in the presence of only 0.5
      mg metronidazole g(-1) soil, the density of protozoa in the rhizosphere was
      reduced by a 10-fold.

PMID- 11999766
TI  - Organochlorine pesticides and polychlorinated biphenyls (PCBs) in eggs of red
      legged frogs (Rana aurora) and northwestern salamanders (Ambystoma gracile) in an
      agricultural landscape.
AB  - Organochlorine pesticides were widely used in the past in Sumas Prairie, British
      Columbia, Canada. In the 1990s, the hatching success of amphibians from
      agricultural sites was significantly depressed in the Sumas Prairie compared to
      reference sites. Therefore, in this study, organochlorine pesticides and
      polychlorinated biphenyls (PCBs) were measured in eggs of red-legged frogs (Rana
      aurora) and northwestern salamanders (Ambystoma gracile) from the Sumas Prairie.
      Egg masses were sampled from three agricultural sites that were exposed to
      agricultural runoff, and three reference sites that had lower agricultural runoff
      exposures. Not only was there little difference in contamination between
      agricultural and reference sites, but the levels of pesticides and PCBs found
      were lower than the concentrations reported to cause developmental or behavioural
      problems in amphibians.

PMID- 11999767
TI  - Seasonality of contamination, toxicity, and quality values in sediments from
      littoral ecosystems in the Gulf of Cadiz (SW Spain).
AB  - To seasonally evaluate littoral contamination, toxicity and quality values of
      sediments from the Gulf of Cadiz, we measured chemical concentrations and
      conducted toxicity tests in winter and summer and linked these results by means
      of multivariate analysis. Sediment samples were subjected to two separate,
      replicated sediment toxicity tests (Microdeutopus gryllotalpa amphipod survival,
      and Ruditapes philippinarum clam reburial), and to comprehensive sediment
      chemistry analyses (grain size, organic carbon, 14 heavy metals, and the
      surfactant linear alkylbenzenesulfonate (LAS)). Only sediments associated with an
      untreated urban discharge were toxic and related to high levels of surfactant
      LAS, Ag, and Pb. Multivariate analysis indicated that variables and chemicals
      associated with geochemical matrix and background levels (specific surface, Fe,
      Zn, Cu, V, Ni, and Co), chemicals associated with untreated urban discharge
      sources, and toxicity effects showed no seasonal variability. Only copper
      concentrations showed seasonal differences, being toxic during the winter and not
      toxic during summer. Multivariate analysis permits us to derive sediment quality
      values (SQVs); in terms of concentrations at or below which biological effects
      were not measured (mg kg(-1) dry sediment), are: LAS, 2.6; lead, 66.8; silver,
      0.78; copper, 69.6.

PMID- 11999768
TI  - Structure-activity relationships and response-surface analysis of nitroaromatics
      toxicity to the yeast (Saccharomyces cerevisiae).
AB  - Inhibition of growth of the yeast Saccharomyces cerevisiae (Cmiz, the minimum
      concentration that produced a clear inhibition zone within 12 h) for 24
      nitroaromatic compounds was investigated and a quantitative structure-activity
      relationship (QSAR) developed based on hydrophobicity expressed as the l
      octanol/water partition coefficient in logarithm form, log K(ow),
      electrophilicity based on the energy of the lowest unoccupied orbital (E(lumo)).
      All nitrobenzene derivatives exhibited enhanced reactive toxicity than baseline.
      The toxicities of mono-nitrobenzenes and di-nitrobenzenes were elicited by
      different mechanisms of toxic action. For mono-nitro-derivatives, both
      significant log K(ow) based and strong E(lumo)-dependent relationships were
      observed indicating that their toxicities were affected both by the penetration
      process and the interaction with target sites of interaction. The toxicities of
      di-nitrobenzenes were greater than mono-nitrobenzenes and no log K(ow)-dependent
      but highly significant E(lumo)-based relationship was obtained. This suggests
      that toxicity of di-nitrobenzenes was highly electrophilic and involved mainly
      their in vivo electrophilic interaction with biomacromolecules. In an effort to
      model the elevated toxicity of all nitrobenzenes, a response-surface analysis was
      performed and this resulted in a highly predictive two-variable QSAR without
      reference to their exact mechanisms (Cmiz = 0.41 log K(ow) - 0.89 E(lumo) - 0.46,
      r2 = 0.87, Q2 = 0.86, n = 24).

PMID- 11999769
TI  - Preliminary examination of contaminant loadings in farmed salmon, wild salmon and
      commercial salmon feed.
AB  - This pilot study examined five commercial salmon feeds, four farmed salmon (one
      Atlantic, three chinooks) and four wild salmon (one chinook, one chum, two
      sockeyes) from the Pacific Coast for PCBs (112 congeners), polybrominated
      diphenylethers (PBDEs - 41 congeners), 25 organochlorine pesticides (OPs), 20
      polycyclic aromatic hydrocarbons (PAHs), and methyl and inorganic mercury. The
      farmed salmon showed consistently higher levels of PCBs, PBDEs, OPs (except
      toxaphene) than the wild salmon. The mean concentrations in pg/g were 51,216 vs
      5302 for total PCBs; 2668 vs 178 for total PBDEs; 41,796 vs 12,164 for total OPs
      (except toxaphene). The farmed salmon levels are likely a consequence of the
      elevated level of contamination found in the commercial salmon feed (mean
      concentrations in pg/g were 65,535 for total PCBs; 1889 for total BPDEs; 48,124
      for total OPs except toxaphene). Except for a single high wild chinook value,
      PAHs were highest in the feed samples followed by the farmed fish and the three
      other wild fish. The Bio-Oregon-1996 feed of hatchery origin showed a level of
      PAHs ten times higher than any other feed. The genotoxic implications of such a
      high PAH level are considered for juvenile chinook salmon. Toxaphene and methyl
      mercury concentrations were not notably different between the wild and farmed
      salmon. There was no clear low contaminant brand of salmon feed. The human health
      implications of eating farmed salmon are considered from the perspective of the
      current WHO and Health Canada (2000) tolerable daily intake (TDI) values for
      PCBs. Based on a TDI of 1 pg TEQ/kg bw/day, this analysis indicated a safety
      concern for individuals who on a regular weekly basis consume farmed salmon
      produced from contaminated feed.

PMID- 11999770
TI  - Biological activity of soil organic matter mobilized by root exudates.
AB  - In order to study the biological activity of soil organic matter mobilized by
      agrarian (Zea mays: cultivars Mytos and Samantha) and forest (Picea abies Karst.
      and Pinus sylvestris L.) root exudates, two different soils, an Eutric Cambisol
      (EC) and a Rendzic Leptosol (RL), were considered. Soil organic matter extracts
      were obtained by treating the soils with water (control) or plant root exudates.
      The extracts were characterized by hormone-like activities and gas
      chromatographic/mass spectrometric (GC/MS) measurements. Their effects on the
      nitrogen metabolism in maize seedlings were evaluated. The nitrogen
      organification in the maize seedlings has been greatly stimulated by all the
      organic acid extracts from the agrarian soil, while the extracts from the forest
      soil had no influence upon the metabolism; this indicated a probable link between
      the plant and the environment. The different biological activities of the
      extracts are discussed.

PMID- 11999771
TI  - Study of the enantioselective elimination of four toxaphene congeners in rat
      after intravenous administration by high resolution gas chromatography negative
      ion mass spectrometry.
AB  - This study was performed to investigate the possible enantioselective metabolism
      of the four chlorinated bornanes: #26, #32, #50 and #62 (according to the Parlar
      nomenclature) by rats. Rats were exposed to a mixture of these toxaphenes by a
      single intravenous injection. Enantiomer ratios (ER) as well as the enantiomer
      fractions (EF) were determined in brain, adipose tissue and liver samples at six
      time intervals by high resolution gas chromatography (HRGC) coupled to negative
      ion chemical ionization (NICI) mass spectrometry (MS). Capillaries coated with
      heptakis-(2,3,6-O-tert-butyldimethylsilyl)-beta-cyclodextrin (TBDMS-CD) or
      octakis-(2,3,6-tri-O-ethyl)-gamma-cyclodextrin (TEG-CD) were used for the
      enantioselective separations. Significant time-dependent changes of ER and EF
      were found in all the three tissues for #26, #50 and #62. Greatest deviations
      from racemic composition were found in the liver, which is known to be the major
      metabolizing organ for toxaphenes. #32 was metabolized the fastest, but showed no
      changes in ER. Brief information is also included about the possible reasons for
      the different behaviors of the four congeners in the studied tissues.

PMID- 11999772
TI  - The statistical merits of various methods of calculating transfer coefficients
      between environmental media--development of the ideal formula for data-sets with
      a log-normal distribution.
AB  - The statistical treatment of data-sets from environmental pollutant studies in
      which different measurements are combined to produce averages or comparative
      factors (e.g., transfer coefficients (TCs), input-output balance values) are
      considered here, with particular reference to the analysis of data from input
      output balance studies of pollutants such as PCBs in animals and humans. Many
      methods of statistical analysis ignore the fact that all measurements are subject
      to error, and generally assume that the normal distribution applies to all data
      sets, which is commonly inappropriate for environmental (and particularly
      biological system) data. Considerably different estimations can be obtained by
      applying different, commonly used, statistical methods, as shown in a simulation
      study presented here and when applied to data from an input-output balance study
      of PCBs in humans. Alternative average and combined factor estimators for the
      treatment of data from these types of studies that give considerable advantages
      in terms of bias and the ease of assessment of accuracy are proposed.

PMID- 11999773
TI  - Combined effects of cadmium and composted manure to aquatic organisms.
AB  - To evaluate the interactive toxicity of cadmium (Cd) and composted manure to
      aquatic organisms 96 h static bioassays were conducted in the laboratory with fry
      of common carp (Cyprinus carpio), copepod (Diaptomusforbesi) and oligochaete worm
      (Branchiura sowerbyi). Five concentrations of composted manure (0, 0.25, 0.5, 1.0
      and 6.7 g/l) were prepared from the aquatic weed, Pistia stratiotes and each of
      them was combined with several concentrations of Cd to determine 96 h LC-50
      values of Cd for the test organisms. Addition of composted manure, irrespective
      of concentration, significantly reduced the LC-50 value of Cd to the copepod and
      common carp fry while it increased the LC-50 value of Cd to the worm. Increased
      susceptibility of the worm to combined treatment of composted manure and small
      concentrations of Cd could be revealed only from the dose mortality curve.
      Results of acute toxicity bioassays were different from the results of bioassays
      conducted with small concentrations of Cd. Worms, exposed to 2.5 mg/l Cd,
      accumulated more Cd than did the carp fry and copepod. Accumulation of Cd by
      worms was increased by the addition of 6.7 g/l composted manure while it
      decreased in the carp fry and copepod. Food consumption rate of common carp
      fingerling was significantly reduced relative to the control by exposure to 2.5
      mg/l Cd. No change in feeding rate was observed when Cd was combined with
      composted manure (6.7 g/l).

PMID- 11999774
TI  - Development of an immuno-immobilized androgen receptor assay (IRA) and its
      application for the characterization of the receptor binding affinity of
      different pesticides.
AB  - Pesticides are synthetic chemicals used not only for improving food and feed
      production but also for the protection of materials and of human health and well
      being. Some of these substances are suspected for adverse effects attributable to
      an interaction with the endocrine system of vertebrates by mimicking or
      inhibiting endogenous hormones. One of the biological targets important in this
      relation is the androgen receptor (AR). To be able to screen environmental
      samples for the presence of compounds which might interfere with androgen action,
      we aimed to develop a receptor assay based on recombinant human AR (rhAR). We
      herein describe an rhAR assay in which the receptor is immobilized in microtiter
      plates via a specific antibody. The assay can be used for high throughput
      screening of chemicals spread into the environment. 29 of the most recommended
      pesticides of the Federal Country Hessen, Germany, were tested for their ability
      to displace [3H]-DHT bound to the rhAR. This evaluation included the major part
      of the most common herbicides, insecticides and fungicides and covered three
      potential groups of endocrine disrupting chemicals. For 28 of the substances
      evaluated, the relative binding affinity to the rhAR was below 0.1% when compared
      to dihydrotestosterone (DHT) (100%), only fentinacetate exhibited an affinity of
      1.42%. An exchange assay indicated that the binding inhibition was reversible. In
      consequence, fentinacetate seems to be a hormonally active substance which may be
      present in vegetables or fish, but also on clothing. We conclude that further
      investigations on this compound and its metabolites are necessary.

PMID- 11999775
TI  - Validating the enchytraeid reproduction test: organisation and results of an
      international ringtest.
AB  - In this paper the experiences concerning the organisation and results of the
      enchytraeid reproduction test (ERT) ringtest are summarised (for details see J.
      Rombke, T. Moser, Organisation and Performance of an International Ringtest for
      the Validation of the Enchytraeid Reproduction Test, vols. I and II. UBA-Texte
      4/99, 1999, 150, 223 pp). The performance of this ringtest was in line with
      requirements published by OECD. It was sponsored by the German Federal
      Environmental Agency (Umweltbundesamt; UBA, Berlin). The UBA was also actively
      engaged (together with the European Chemicals Bureau, Ispra) in a scientific task
      force, which consisted of seven scientists experienced in terrestrial ecology and
      ecotoxicology. 29 institutions (mainly from universities and contract research
      laboratories) from 15 countries of Europe and North America participated actively
      in the ringtest. The co-ordinating laboratory centrally distributed the test
      chemicals, guidance papers and test organisms to all participants. In addition,
      several training courses were organised. Most participants performed two tests
      with the fungicide Carbendazim and two with 4-nitrophenol. For each chemical, one
      test was designed according to an ECx approach and the other according to an NOEC
      approach. Several aspects of the test protocol were modified based on the
      experiences gained during the ringtest. A major aspect of the project was the
      detailed statistical evaluation of the test results (for details see A. Weyers,
      J. Rombke, T. Moser, T. Ratte, Results of and statistical implications from the
      enchytraeid reproduction ringtest, 2001, submitted), leading to recommendations
      for an optimised ecotoxicological test design. A total of 92 tests were performed
      according to the protocol which is among the highest number ever performed in a
      ringtest. About 72% met the validity criteria (control mortality < 20%, > 25
      juveniles per 10 adults). The effects of the two test chemicals on enchytraeid
      reproduction were in the range expected from data in the literature on
      oligochaete toxicity. However, statistical evaluation of the data was sometimes
      difficult as a result of the high variability in the number of juveniles. This
      variability was caused by several reasons, including hormesis effects or lack of
      experience of some participants. Comparison of the data from the NOEC and ECx
      approaches pointed to a clear advantage in favour of the latter. In most cases
      EC10 values were lower than the NOEC values determined in the same test. For
      details see A. Weyers et al. (loc. cit.). Reproducibility of the test data and
      practicability of the ERT ringtest were of the same order of magnitude as other
      ringtests recently performed. As a result of the ringtest, the ERT draft
      guideline was significantly improved. The new version is currently being
      standardised by OECD, ISO and ASTM.

PMID- 11999776
TI  - Response of Ceriodaphnia dubia to ionic silver: discrepancies among model
      predictions, measured concentrations and mortality.
AB  - Silver thiosulfate, often a waste product of photoprocessing, is less
      bioavailable or toxic to aquatic organisms than is ionic silver. We conducted
      duplicate 48-h Ceriodaphnia dubia tests in reconstituted laboratory water using
      treatments of 92.7 nM Ag+ with various concentrations of thiosulfate. Expected
      Ag+ concentrations were generated for thiosulfate treatment levels using MINEQL +
      chemical equilibrium modeling. Ag+ concentrations in treatments were determined
      using a novel silicon-based sensor. Based on predicted Ag+ and published 48-h
      LC50 values for C. dubia, we did not expect to observe adverse effects. Yet, 100%
      mortality was observed at low thiosulfate treatments, whereas > 85% and > 95%
      survival was observed at higher thiosulfate treatment levels, respectively. Our
      results indicate that biotic responses match the sensor-based Ag+ concentrations.
      However, there is a discrepancy between these empirical results and responses
      expected to occur with Ag+ concentrations as predicted by MINEQL + chemical
      modeling. By correlating silicon sensor data with toxicity results obtained from
      our laboratory, our work clearly relates a specific chemical form (Ag+) to
      toxicity results.

PMID- 11999777
TI  - Toxicity evaluation of new antifouling compounds using suspension-cultured fish
      cells.
AB  - A simple, rapid toxicity test was developed using the suspension-cultured fish
      cell line CHSE-sp derived from chinook salmon Oncorhynchus tshawytscha embryos in
      order to assess the toxicity of new marine antifouling compounds. The compounds
      tested were copper pyrithione, Diuron, Irgarol 1051, KH101, Sea-Nine 211, and
      zinc pyrithione, all of which have been nominated in Japan as possible
      replacements for organotin compounds. The in vitro acute toxicity (24-h EC50) of
      the six compounds to these fish cells was evaluated using the dye Alamar Blue to
      determine cell viability, and then correlated with the results of in vivo chronic
      toxicities (28-day LC50) to juvenile rainbow trout Oncorhynchus mykiss. The
      suspension-cultured fish cells were found to be suitable for the screening of
      such chemicals before performing an in vivo test. The toxicities of the test
      compounds obtained from both tests, shown in decreasing order, were as follows:
      copper pyrithione > zinc pyrithione > KH101 > or = Sea-Nine 211 > Diuron >
      Irgarol 1051. The herbicides Diuron and Irgarol 1051 showed the least toxicity,
      while the pyrithiones had the greatest toxicity.

PMID- 11999778
TI  - Effects of bensulfuron-methyl and cinosulfuron on growth of four freshwater
      species of phytoplankton.
AB  - The acute toxicity of sulfonylurea herbicides bensulfuron-methyl and cinosulfuron
      was tested on the five species of freshwater phytoplankton: Scenedesmus acutus,
      Scenedesmus subspicatus, Chlorella vulgaris and Chlorella saccharophila.
      Herbicide concentrations eliciting a 50% growth reduction over 96 h (EC50) ranged
      from 8 to 104 mg/l for cinosulfuron and from 0.015 to 6.2 mg/l for bensulfuron
      methyl. The pesticides bensulfuron-methyl, atrazine and benthiocarb were more
      toxic than cinosulfuron, chlorsulfuron, molinate, fenitrothion and
      pyridaphenthion in a toxicity study with the same algal species. The
      transformation of effective concentrations of bensulfuron-methyl and cinosulfuron
      and other pesticides, obtained from toxicity measurements, into percent of the
      saturation level in water is used as a first evaluation of potential hazard to
      aquatic systems. The herbicides cinosulfuron, methyl-bensulfuron, atrazine and
      chlorsulfuron were more dangerous than the herbicides benthiocarb and molinate
      and than the insecticides fenitrothion and pyridaphenthion, in a study of hazard
      evaluation. The two species of Chlorella were more tolerant to both herbicides
      than the two species of Scenedesmus. A potential environmental hazard of
      sulfonylurea herbicides to aquatic systems has to be expected even at low
      environmental concentrations.

PMID- 11999779
TI  - Chemical and bacterial changes during laboratory conditioning of formulated and
      natural sediments.
AB  - Within the framework of toxicity testing using formulated sediment, a
      conditioning treatment prior to toxic contamination has been examined. This
      preliminary step enables the bacterial colonisation of the sediment, the
      initiation of organic matter degradation, and the establishment of stable
      biological and physico-chemical conditions. The treatment involved in keeping the
      formulated sediment under water in conditions similar to that chosen for toxicity
      tests. The behaviour of a formulated sediment was compared with a natural
      sediment. The monitoring of physico-chemical and biological parameters of
      sediment and water column was carried out over a 30-day incubation in two
      laboratories. The parameters of pH and redox, dissolved organic carbon (DOC), NH4
      and NO2, total organic carbon (TOC) were measured. The bacterial community was
      characterised by the determination of bacterial density, in total bacteria number
      or colony forming units (CFU), several exoenzymatic activities (P-glucosidase,
      xylosidase, leucine-amino-peptidase phosphatase and sulfatase activities), and
      three gas productions (CO2, N2O and CH4). The same experiment was carried out
      with a natural sediment. A 10- to 15-day conditioning allowed a physico-chemical
      stabilisation and corresponded to kinetic changes in hydrolysis activities. As
      compared to data of the natural sediment, the biological activity of the
      formulated sediment showed a different dynamic with lower activity levels. For
      both sediments, an important decrease of activities levels was observed after 15
      days because of a substrate limitation. The work showed that a preliminary
      conditioning treatment of a formulated sediment provides the stabilisation of
      parameters that can affect toxicant bioavailability. Additional research is
      needed to determine the real influence of conditioning on the bioavailability of
      contaminants. The possible advisability of organic matter input, to maintain the
      sediment bacterial activity, has to be studied.

PMID- 11999780
TI  - Determination of tissue-blood partition coefficients for a physiological model
      for humans, and estimation of dioxin concentration in tissues.
AB  - The tissue-blood partition coefficients for a physiologically based
      pharmacokinetic (PBPK) model were determined, and the concentrations of 17
      congeners of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans
      (PCDD/Fs) in tissues in Japanese people were estimated using the model. According
      to the PBPK model established by Lawrence and Gobas [Chemosphere 35 (1997) 427
      452], we assumed a steady-state fugacity model for Japanese people in general,
      and set the route of PCDD/Fs exposure only from food intake. The required
      partition coefficients for liver, kidney, adipose, muscle, skin, bile, gut and
      viscera (richly perfused tissue) were calculated using available autopsy data
      from eight Japanese men and women who were not accidentally exposed to PCDD/Fs.
      For validation of the partition coefficients, estimated PCDD/F concentrations in
      liver, kidney, fat, blood and muscle using the model were compared to other two
      sets of measured concentration data in Japanese tissues. Good agreement was
      obtained between estimated data and measured data, and most of the measured data
      were within the simulated concentration range in liver, kidney, blood and muscle.
      From these results, our model and calculated partition coefficients seem
      applicable for the estimation of congener-specific concentrations in human
      tissues.

PMID- 11999781
TI  - Time-dependent toxicity in the long-term inhibition assay with Vibrio fischeri.
AB  - The significance of the duration of exposure for the detection of toxicity was
      evaluated in a 24 h long-term bioluminescence inhibition assay with Vibrio
      fischeri. Bioluminescence was measured over the time course of 24 h using
      microplates. The undisturbed luminescence of controls in this assay exhibited
      characteristic dynamics: a decrease within a period of 12 h with minimal
      luminescence followed by a continuous increase of luminescence beyond the
      starting value. To evaluate the toxic influence of compounds chosen to reflect
      immediate and delayed toxicity to V. fischeri, the bioluminescence was measured
      for 24 h at 30 min intervals. Luminescence inhibition patterns were recorded for
      subdinoseb, pentachlorophenol and 2,4,5-trichlorophenol) and for substances
      causing delayed toxicity (chloramphenicol, nalidixic acid and phosphomycin). The
      toxic influence of substances with immediate toxicity was observed directly after
      application, whereas the toxicity patterns of substances with delayed toxicity
      developed specifically over the time according to the different involved
      mechanisms of action. It is concluded that knowledge about time to toxicity in
      bioassays is necessary in order to identify suitable test endpoints as well as to
      recognize potential hazards related to time-dependent toxicity.

PMID- 11999782
TI  - Sensitivity of epigean and hypogean freshwater macroinvertebrates to complex
      mixtures. Part I: Laboratory experiments.
AB  - The impact of waste storage on aquatic systems is a regulatory requirement in
      Europe, but it is nowadays only considered to a limited extent. The complexity of
      mixtures, which contain many inorganic and organic compounds, requires the use of
      combining chemical measurements with ecotoxicological observations. This research
      employed an integrated laboratory and outdoor mesocosms approach to assess the
      effects of mixtures on freshwater macroinvertebrates. The effects of percolates
      coming from water having percolated through maturated secondary smelting slags,
      on freshwater macroinvertebrates (molluscs, crustaceans and insect larvae) were
      investigated under laboratory conditions using a continuous flow-through testing
      apparatus. Lethality (LC50 96 and 240 h) was chosen as the endpoint. The results
      indicate that the difference in sensitivity of macroinvertebrates is correlated
      with their ability to regulate or neutralize contaminants in the mixture during
      short-term exposure. Moreover, differences in sensitivity were dependent on
      duration of exposure. Because of the variability of toxicity among mixtures
      coming from the same waste, bioassays are required to determine the toxicities of
      these mixtures.

PMID- 11999783
TI  - The significance of brominated flame retardants in the environment: current
      understanding, issues and challenges.

PMID- 11999784
TI  - An overview of brominated flame retardants in the environment.
AB  - The presence of brominated flame retardant (BFR) chemicals, and particularly
      polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA) and
      hexabromocyclododecane (HBCD), has become of increasing concern to scientists
      over the past decade. Environmental studies conducted primarily in Europe, Japan
      and North America indicate that these chemicals are ubiquitous in sediment and
      biota. The levels of PBDEs seem to be increasing, and several trends, including
      in humans, indicate that this increase may be rapid. The occurrence of high
      concentrations of certain PBDE isomers may be sufficient to elicit adverse
      effects in some wildlife. There is also concern that levels could cause adverse
      effects in sensitive human populations such as young children, indigenous
      peoples, and fish consumers. However, our knowledge about these chemicals, their
      sources, environmental behavior, and toxicity is limited, making risk assessment
      difficult. In this paper, the current state of knowledge is reviewed and areas
      for further research recommended to improve future monitoring and risk assessment
      efforts.

PMID- 11999785
TI  - First world-wide interlaboratory study on polybrominated diphenylethers (PBDEs).
AB  - The first world-wide interlaboratory study on PBDEs, organised between November
      1999 and April 2000, involved five biological samples, two sediments and two
      standard solutions. These materials were sent to 26 participants in nine
      different countries. Results were returned from 18 laboratories. The results
      reported for BDE 47 were acceptable with a range of relative standard deviations
      (Rsd) of 17-40%. Results for the BDEs 99 (Rsd 25-77%), BDE 100 (Rsd 19-48%), 153
      (Rsd 30-48%) and 154 (Rsd 25-43%) showed that a further improvement of these
      analyses is needed. The BDE 209 analysis is not under the control of the
      participating laboratories. The data reported for the biota samples were very
      variable and for the two sediments Rsd values of 48% and 78% were obtained. It is
      recommended that analysts pay more attention to the special requirements for the
      BDE 209 analysis such as avoiding exposure to intensive light and exposure for
      too long times to too high temperatures.

PMID- 11999786
TI  - Analysis of mono- to deca-brominated diphenyl ethers in chickens at the part per
      billion level.
AB  - Polybrominated diphenyl ethers (PBDEs) are flame retardants which have been found
      to be increasing in the environment. Because of structural similarities to the
      polychlorinated biphenyls and concerns that PBDEs may be widespread, we have
      investigated their presence in a food source, namely chickens. A GC-MS method was
      developed to analyze mono- through deca-BDEs in chicken fat samples. The method
      utilized GC pressure programming and selected ion monitoring to quantitate PBDEs
      at the low part per billion level. Four 13C-labeled surrogates were used to
      determine recoveries; recoveries averaged from 76% to 114%. Thirteen chickens
      from the Southern US and a composite sample of chickens from North Dakota were
      analyzed by this method. The total concentrations of PBDEs on a whole weight
      basis ranged from 1.7 ppb in North Dakota chickens to 39.4 ppb in a chicken from
      Arkansas. On a lipid weight basis, these levels were lower than those generally
      found in fish and fish-eating mammals. The PBDE pattern was also different from
      other samples reported; penta-BDEs rather than tetra-BDEs were the most prominent
      congeners.

PMID- 11999787
TI  - Comparing electron ionization high-resolution and electron capture low-resolution
      mass spectrometric determination of polybrominated diphenyl ethers in plasma,
      serum and milk.
AB  - Gas chromatography coupled to low-resolution mass spectrometry with electron
      capture negative ionization as detection mode (GC-LRMS (ECNI)) has been compared
      to gas chromatography coupled to high-resolution mass spectrometry using electron
      ionization as detection mode (GC-HRMS (EI)) for determination of polybrominated
      diphenyl ethers (PBDEs) in biological samples. Extracts of 5.0 g plasma, serum
      and milk samples were analyzed using both methods. The GC-LRMS (ECNI) and GC-HRMS
      (EI) systems were found to be equally well suited for determination of PBDEs in
      the biological samples, as well as in standard solutions, with respect to
      response, detection limits and repeatability at the pg-level. The estimated
      limits of detection (LOD) in milk extracts ranged from 0.3-0.6 pg PBDE/g milk and
      0.4-0.7 pg PBDE/g milk, for the GC-LRMS (ECNI) and GC-HRMS (EI) systems,
      respectively. The method repeatability including sample preparation was in the
      range 4.7-8.4% and 0.6-10% relative standard deviation (RSD) for the GC-LRMS
      (ECNI) and GC-HRMS (EI) systems, respectively.

PMID- 11999788
TI  - Occurrence and congener profiles of polybrominated diphenyl ethers (PBDEs) in
      environmental samples from coastal British Columbia, Canada.
AB  - Environmental levels and detailed congener profiles (31 congeners and 3 coeluting
      congener groups) of polybrominated diphenyl ethers (PBDEs) were assessed in a
      number of biota samples taken over a large geographic range covering harbours and
      industrial sites on Canada's West Coast. Additionally, PBDE congener profiles
      were determined using semipermeable membrane devices (SPMDs) deployed in the
      Fraser River, the river in Western Canada with the largest industrial activity.
      PBDE levels detected in biota were between 4 and 2300 ng/g lipid and these levels
      were compared with those reported in selected European biota to provide a wider
      perspective on PBDE contamination on Canada's West Coast. Thirteen-congener PBDE
      patterns in the environmental samples were examined using principal component
      analysis (PCA), and additionally, comparisons were made between the PBDE profiles
      in the sample groups and commercially used PBDE technical mixtures (e.g.,
      Bromkals) on a percent composition basis. PCA on congener specific data revealed
      that PBDE patterns are remarkably similar over a wide geographical range in
      Western Canada, however, the general pattern in environmental samples varies
      significantly from those of the predominant technical mixtures. Finally,
      correlations between PBDE and other persistent and toxic co-occurring
      contaminants found in Dungeness crab were determined.

PMID- 11999789
TI  - Spatial distribution of polybrominated diphenyl ethers and polybrominated
      biphenyls in lake trout from the Laurentian Great Lakes.
AB  - Concentrations of two types of brominated flame-retardants (BFRs); polybrominated
      diphenyl ethers (PBDEs) and polybrominated biphenyls (PBBs) were determined in a
      single age class of lake trout (Salvelinus namaycush) collected from the
      Laurentian Great Lakes in 1997. Mean concentrations of total PBDE were highest in
      samples from Lake Ontario at 95+/-22 ng/g wet weight (ww) or 434+/-100 ng/g lipid
      weight (lw) while the lowest concentrations were observed in Lake Erie lake trout
      (27+/-8.6 ng/g ww, 117+/-37 ng/g lw). In all samples, the predominant PBDE
      congeners were 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5
      pentabromodiphenyl ether (BDE-99), and 2,2',4,4', 6-pentabromodiphenyl ether (BDE
      100), which are the primary components of the commonly used penta-BDE formulation
      flame retardant. Lake trout collected from Lake Huron had the highest
      concentrations of PBBs (3.1+/-1.7 ng/g ww, 15+/-8.5 ng/g lw), while the lowest
      levels were detected in fish from Lake Superior (0.25+/-0.13 ng/g ww, 1.7+/-0.89
      ng/g lw). In all lake trout samples, 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), a
      major constituent of the flame-retardant FireMaster BP-6, was the predominant PBB
      congener.

PMID- 11999790
TI  - Polybrominated diphenyl ethers in two species of marine top predators from
      England and Wales.
AB  - During an earlier study, polybrominated diphenyl ethers were detected at high
      concentrations in fish and sediments downstream of a manufacturing site in NE
      England. We have now undertaken analysis of 14 tri- to heptabromodiphenyl ether
      congeners in tissues of two species of marine top predators exposed to these
      compounds through their consumption of fish. In this paper we report data for 47
      cormorants and 60 harbour porpoises from England and Wales, sampled during the
      period 1996-2000. Concentrations of the summed congeners ranged from 1.8 to 140
      microg kg(-1) wet weight in cormorant livers, and from not detected to 6900
      microg kg(-1) wet weight in porpoise blubber. The major congeners present were
      generally BDE47, BDE99 and BDE100. There was little correlation between
      concentrations of chlorobiphenyls (as the sum of 25 individual congeners) and the
      sum of the 14 BDE congeners determined, particularly for the porpoises.

PMID- 11999791
TI  - Levels of some polybrominated diphenyl ether (PBDE) flame retardants along the
      Dutch coast as derived from their accumulation in SPMDs and blue mussels (Mytilus
      edulis).
AB  - Aqueous concentrations of individual brominated diphenyl ethers (BDEs) were
      determined for five stations in the Scheldt estuary and the North Sea along the
      Dutch coast using passive sampling by semipermeable membrane devices (SPMDs).
      Values of 0.1-5 pg l(-1) were observed. The highest levels were found in the
      Scheldt estuary. Concentration differences between February and October were a
      factor of 4-8 for BDE209, and were smaller than a factor of 2 for the other BDEs.
      Bioaccumulation was studied for native mussels and for mussels that were
      transplanted from an uncontaminated area into the Scheldt estuary for 6 weeks.
      Concentrations in native mussels were higher by a factor of 10 and 2 for BDEs and
      PCBs, respectively. Field based bioaccumulation factors (BAFs) were higher for
      BDEs than for PCBs by a factor of 10. Depuration experiments showed that the
      larger part of the BDE209 content in mussels was associated with ingested
      particles, whereas no such effect was observed for the other BDEs or PCBs.

PMID- 11999792
TI  - Comparison of polybrominated diphenyl ethers in fish, vegetables, and meats and
      levels in human milk of nursing women in Japan.
AB  - At present, little is known about the occurrence of polybrominated diphenyl
      ethers (PBDEs) in fish and food products sold in Japan. To investigate whether
      human exposure to PBDEs through the diet is significant, the concentrations of
      PBDEs were determined in fish and in meat and vegetables sold in two food markets
      in the city of Hirakata, Osaka prefecture. The concentrations of PBDEs in the
      breast milk of 12 primiparae nursing women at one month after delivery also were
      determined to ascertain the relationship between the levels found in the diet and
      levels in humans. sigma PBDE concentrations ranged between 21 and 1650 pg/g fresh
      weight in the edible tissues of five species of fish and one shellfish species.
      The highest concentrations were measured in yellow-fin tuna, followed by short
      necked clam, salmon, yellowtail, mackerel and young yellowtail. Interestingly,
      sigma PBDE concentrations were not statistically significantly different in two
      cultured mackerel samples from Japan and mackerel collected from northern
      European waters. sigma PBDE concentrations in beef, pork and chicken meat
      (ranging between 6.25 and 63.6 pg/g fresh weight) and in three different
      vegetables (ranging between 38.4 and 134 pg/g fresh weight) were significantly
      lower than the concentrations in fish. In human milk, sigma PBDE concentrations
      ranged between 668 and 2840 pg/g lipid basis, which is comparable to the levels
      in populations of nursing women reported in Sweden and elsewhere. There was a
      strong positive relationship between PBDE concentrations in human milk and
      dietary intake of fish and shellfish, which was established in the women from
      responses to a questionaire on food consumption habits. The results of this study
      of food products commonly consumed in Japan and the levels found in nursing women
      raise a concern about low level PBDE contamination of fish and other foods
      intended for human consumption.

PMID- 11999793
TI  - PBDEs in the San Francisco Bay Area: measurements in harbor seal blubber and
      human breast adipose tissue.
AB  - To explore the levels of polybrominated diphenyl ethers (PBDEs) in California,
      samples from 11 archived harbor seals (Phoca vitulina Richardsi) from the San
      Francisco Bay and breast adipose tissue samples from 23 women were analyzed. The
      levels of PBDEs in human tissue samples were in the low ng/g fat range, with
      PBDEs 47, 153, 154, 99, and 100 as the major congeners. Average sigma PBDEs (86
      ng/g fat) in these California women are the highest human levels reported to
      date. An inverse relationship between concentration of PBDEs and age of these
      women was apparent. The levels of PBDEs measured in harbor seal blubber were in
      the low ng/g to low microg/g fat range, with the same major congeners as those
      measured in the human tissues. PBDE 47 was the highest among all congeners
      measured in both human tissue and seal blubber samples. The concentrations of
      PBDEs in harbor seals in the San Francisco Bay have increased dramatically over
      the past decade, with current levels among the highest reported for this species.

PMID- 11999794
TI  - Exposure to polybrominated diphenyl ethers and tetrabromobisphenol A among
      computer technicians.
AB  - This study investigates exposure to polybrominated diphenyl ethers (PBDEs) and
      tetrabromobisphenol A (TBBPA), which are used as flame retardants in electronic
      equipment, in a group of technicians with intense computer work. Thirteen PBDE
      congeners and TBBPA were quantified in serum from 19 computer technicians.
      Previously investigated groups of hospital cleaners with no computer experience,
      and clerks working full-time at computer screens were used for comparison. The
      computer technicians had serum concentrations of BDE-153, BDE-183 and BDE-209
      that were five times higher than those reported among hospital cleaners and
      computer clerks. The median levels observed among the computer technicians were
      4.1, 1.3, and 1.6 pmol/g lipid weight, respectively. In contrast, for BDE-47
      there was no difference between the computer technicians and the others. BDE-100,
      BDE-203, and three structurally unidentified octa-BDEs and three nona-BDEs, were
      present in almost all samples from the computer technicians. Further, TBBPA was
      detected in 8 out of 10 samples. The levels of BDE-153, BDE-183, and one of the
      octa-BDEs were positively correlated with duration of computer work among
      technicians. On a group level an exposure gradient was observed, from the least
      exposed cleaners to the clerks, and to the highest exposed group of computer
      technicians. A dose (duration of computer work)-response relationship among
      computer technicians was demonstrated for some higher brominated PBDE congeners.
      Thus, it is evident that PBDEs used in computers and electronics, including the
      fully brominated BDE-209, contaminate the work environment and accumulate in the
      workers tissues.

PMID- 11999795
TI  - A comparison of the properties of the major commercial PBDPO/PBDE product to
      those of major PBB and PCB products.
AB  - Decabromodiphenyl oxide (DBDPO), a highly effective polybrominated diphenyl oxide
      (PBDPO) flame retardant (FR) used primarily in electrical and electronic
      equipment, is the second highest volume brominated flame retardant (BFR) and
      accounts for 82% of the PBDPO usage globally. The apparent similarities in
      chemical structure between the DBDPO, polychlorinated and polybrominated biphenyl
      (PCB, PBB) molecules have led to the presumption that these substances also share
      similar toxicological and environmental properties. However, DBDPO's
      physical/chemical properties, applications, environmental release, and toxicology
      differ substantially from the former PCB/PBB products. DBDPO is a heavier and
      larger molecule than components of the predominant PCB/PBB products used in the
      past, and the commercial DBDPO product has a lower water solubility and vapor
      pressure than the former PCB and PBB products. DBDPO's detection in the
      environment is generally in sediments near known point sources, and its primary
      use in thermoplastics limits its environmental release from end products. PBB
      environmental release has been primarily associated with one accident occurring
      in the US in 1973. The PCBs, used in applications with a high potential for
      environmental release, were detected in diverse locations around the world as
      early as in the 1970s. Current releases of PCB are considered related to an
      environmental cycling process of congeners previously released into the
      environment; however, DBDPO's physical/chemical properties do not indicate a
      similar potential. Extensive testing of the DBDPO commercial product has
      demonstrated that it is toxicologically and pharmacokinetically different from
      the predominant PCB and PBB products used in the past. Thus, although the
      chemical structures of DBDPO, PBB, and PCB appear similar, the properties of
      DBDPO are distinctly different.

PMID- 11999796
TI  - Potential role of fire retardant-treated polyurethane foam as a source of
      brominated diphenyl ethers to the US environment.
AB  - Five tetra- to hexabrominated diphenyl ether (BDE) congeners (BDE-47, -99, -100, 
      153 and -154) are the most frequently reported in wildlife and humans. The
      commercial penta-BDE product, used predominantly to flame-retard polyurethane
      foam, consists primarily of these same congeners. In 1999, North American demand
      accounted for 98% of the total global penta-market of 8500 metric tons. Frogs,
      housed with flame retardant-treated polyurethane foam as a dry substrate,
      accumulated 10,100 microg/kg (wet weight) of the above BDEs. Crickets kept
      therein as food contained 14,400 microg/kg. The crickets are believed to have
      browsed directly on the foam and, in turn, were consumed by the frogs. BDE
      congener composition in all three matrices matched that of the penta-commercial
      product. Similar congeners were also observed in soil and stream sediments
      collected near a polyurethane foam manufacturing plant. Summed concentrations of
      BDE-47, -99 and -100, the dominant congeners observed in these samples, ranged
      from < 1 to 132 microg/kg (dry weight basis). Sunfish fillets obtained from a
      nearby, off-site pond contained a total of 624 microg/kg (lipid basis). Sewage
      treatment plant (STP) sludge exhibited these same congeners at 1370 microg/kg
      (dry weight). BDE-209, the fully brominated congener predominant in the
      commercial deca-BDE product, was also present at 1470 microg/kg. While no known
      polyurethane foam manufacturers discharged to this plant, the distribution
      pattern of the low brominated congeners in the sludge matched that of the penta
      product. After four weeks of exposure to ambient outdoor conditions, the surface
      of flame-retarded polyurethane foam became brittle and began to disintegrate.
      Subsequent dispersal of these penta-containing foam fragments may be one
      mechanism by which these BDEs reach the environment.

PMID- 11999797
TI  - Fire-LCA study of TV sets with V0 and HB enclosure material.
AB  - A novel Life-Cycle Assessment model (Fire-LCA) has been defined for the
      determination of the environmental impact of measures taken to attain a high
      level of fire safety. This study, which represents the first application of this
      LCA model, concentrates on a comparison between a TV with an enclosure
      manufactured with a flame retardant (FR) plastic (V0-rated high impact
      polystyrene, HIPS, typical for the US market) and one manufactured with a non
      flame retardant (HB-rated HIPS, typical for the European market). A fire model
      has been defined based on international statistics, which indicate that use of V0
      rated enclosure material essentially removes the risk of TV fires while
      approximately 165 TV fires occur per million TVs in Europe each year where the
      enclosure material is breached. The application of the model indicates that
      emissions of some key species (such as dibenzodioxins and PAH) are actually lower
      for the TV with the FR enclosure than for the TV with the NFR enclosure. This has
      direct reprercussions for the assessment of the environmental impact of the FR TV
      relative to that of the NFR TV. Finally, when considering the risk associated
      with the use of flame retardants, it is also important to consider the risk
      associated with fires. Based on the in-depth analysis of available fire
      statistics, conducted as a part of this study, it has been estimated that as many
      as 160 people may die each year in Europe as a direct result of TV fires and as
      many as 2000 may be injured in the same period.

PMID- 11999798
TI  - A perspective on the potential health risks of PBDEs.
AB  - The polybrominated diphenylethers (PBDEs) are a class of chemicals widely used as
      flame retardants. Concentrations of PBDEs in some human and marine mammal
      populations are increasing. The toxicological endpoints of concern for
      environmental levels of PBDEs are likely to be thyroid hormone disruption,
      neurodevelopmental deficits and cancer. Unfortunately, the available
      toxicological evidence for these endpoints is surprisingly limited, given their
      widespread use, bioaccumulative potential, and structural similarity to thyroid
      hormones and polychlorinated biphenyls (PCBs). Available evidence suggests that
      the PBDE congeners likely to bioaccumulate (i.e., those observed in human tissues
      and other biota) have the propensity to disrupt thyroid hormones, cause
      neurobehavioral deficits and possibly cause cancer in laboratory animals. It is
      unclear whether current concentrations of PBDEs in human tissues would be
      expected to adversely impact human health. Since nearly all individuals are
      exposed to low levels of PBDEs, the potential health impacts also should include
      assessment at the population level. This paper summarizes the available
      toxicological evidence for PBDE-induced thyroid hormone disruption,
      neurodevelopmental deficits, and, for some congeners, cancer, and provides a
      perspective on the potential risks of the PBDEs for human health.

PMID- 11999799
TI  - The toxicology of the three commercial polybrominated diphenyl oxide (ether)
      flame retardants.
AB  - Three commercial polybrominated diphenyl oxide flame retardants (PBDPO, PBDE) are
      manufactured: decabromodiphenyl oxide (DBDPO), octabromodiphenyl oxide (OBDPO)
      and pentabromodiphenyl oxide (PeBDPO). The composition, production volumes, uses
      and toxicology of the three products differ. In 1999, DBDPO accounted for
      approximately 82% of the global PBDPO usage. DBDPO has been extensively tested.
      DBDPO was not acutely toxic, was not irritating to the skin or eye, and did not
      induce skin sensitization. No evidence of genotoxic effects was detected in the
      Ames Salmonella, chromosome aberration, mouse lymphoma, or sister chromatid
      exchange tests. No cytogenic changes were observed in the bone marrow of rats
      (parents and offspring) undergoing a one-generation reproduction test. DBDPO did
      not adversely affect development or reproduction in rats. DBDPO's no-adverse
      effect-level (NOAEL) in repeated dose studies was > or = 1000 mg/kg body weight.
      No, equivocal, or some evidence of carcinogenicity, dependent on genus and sex,
      was found in mice and rats at 2.5% and 5% of the diet administered for 2 years.
      DBPDO was poorly absorbed from the gastrointestinal tract (< 0.3-2% oral dose),
      had a short half-life (< 24 h) compared to PCB 153 (only 2% of an oral dose
      eliminated by rats in 21 days), and was rapidly eliminated via the feces (> 99%
      in 72 h). In contrast, components of the PeBDPO product were well absorbed and
      slowly eliminated, OBDPO's effect level in a 90-day study was approximately 100
      mg/kg, PeBDPO's no-effect-level (NOEL) in a 30-day study was 1 mg/kg, and OBDPO
      induced developmental toxicity in the rat. In aquatic species, neither DBDPO nor
      OBDPO were toxic to aquatic organisms or bioconcentrating. Components of the
      PeBDPO product bioconcentrated in fish but produced little evidence of adverse
      effects.

PMID- 11999800
TI  - Uncertainties and data needs in risk assessment of three commercial
      polybrominated diphenyl ethers: probabilistic exposure analysis and comparison
      with European Commission results.
AB  - Some environmental monitoring programs have reported increasing levels of certain
      polybrominated diphenyl ether (PBDE) isomers in aquatic biota and in human breast
      milk. The commercial PBDE products are known as penta-, octa-, and deca
      brominated diphenyl ethers (PeBDE, OBDE and DBDE, respectively). Aside from the
      current European Commission's risk assessment initiative and efforts underway in
      Sweden, Canada and elsewhere to evaluate environmental levels, little is
      understood about sources of exposure and risks to humans. In this study, a multi
      pathway human health risk assessment was performed to predict theoretical chronic
      daily intakes (CDIs) of PeBDE, OBDE, and DBDE by five different age groups: 0-2,
      2-6, 6-12, 12-18, and 18-70 years. Sources of exposure included air, drinking
      water, consumption of fish, vegetables, meat and dairy products, and ingestion of
      breast milk by infants. In addition to a deterministic analysis, the risk
      assessment included a probabilistic analysis to derive the probability density
      functions describing the range of plausible exposures associated with eight
      different pathways, as well as aggregate lifetime exposures for each age group.
      The results were compared to CDI point estimates calculated by the European
      Chemicals Bureau as part of the European Commission's Existing Substances
      Programme. The major sources of uncertainties are discussed, including
      environmental sources, levels in different environmental compartments, toxicity,
      and human exposure. This paper also discusses the limitations in the current
      state-of-the-science and provides recommendations for improving the scientific
      relevance and accuracy of future environmental risk assessments of PBDEs.

PMID- 11999801
TI  - New developments in influenza vaccine technology: a potential new prevention
      strategy for employers and managed care organizations.
AB  - Influenza is still one of the most wide-reaching, deadly infectious diseases in
      the United States, with an estimated 54 million cases and 42,000 deaths in a
      typical year. At $14 billion, the annual cost of influenza is also enormous. More
      than 80% of that figure comes from so-called indirect medical costs-eg, the
      productivity loss that results when a person with influenza misses work. The
      economic cost makes the disease of special concern to employers, who bear the
      financial burden of such indirect costs, and to the managed care organizations
      that serve them. Although several therapies moderate the severity of influenza
      symptoms, prevention remains the best strategy for reducing the disease's
      morbidity and mortality, as well as the economic cost. Vaccines composed of
      inactivated (ie, killed) virus have been available for more than 50 years, and
      with millions of doses now administered, these inactivated vaccines have earned a
      strong safety record. When the viral strains contained in the vaccine match those
      circulating, efficacy against serologically defined infection can be as high as
      88%. When the match is not good, however, the inactivated vaccine may have
      substantially lower efficacy. Another shortcoming is that the inactivated virus
      vaccine requires injection, which can deter compliance in those who have needle
      phobia or simply dislike getting shots. These concerns have fueled the
      development and application for licensing of a cold-adapted, live-attenuated
      influenza virus vaccine (CAIV), which is administered nasally and is not capable
      of causing disease. Compared with the inactivated vaccine, the CAIV may have
      superior efficacy and appears to have similarly minor systemic side effects. In
      addition, CAIV does not require injection and therefore does not cause local pain
      or tenderness when administered. This article summarizes recent studies of CAIV
      indicating that it is effective and safe. With its likelihood of enhanced
      compliance, its ease of administration, and its potentially superior efficacy,
      CAIV could play a significant role in influenza prevention.

PMID- 11999802
TI  - The effect of a low molecular weight inhibitor of lipid peroxidation on
      ultrastructural alterations to ischemia-reperfusion in the isolated rat heart.
AB  - The effects of H290/51, a novel indenoindole derivative inhibitor of lipid
      peroxidation, on ultrastructural changes during cardiac ischemia-reperfusion
      injury were investigated. Langendorff-perfused rat hearts were exposed to 30
      minutes of global ischemia followed by 20 minutes of reperfusion: Group A:
      Control hearts with standard buffer perfusion with vehicle added. Group B:
      H290/51 (10(-6) mol/l) added to buffer throughout stabilisation and reperfusion.
      In an additional Group C, where hearts were given H290/51, but not subjected to
      ischemia, the ultrastructure was preserved till the end of reperfusion. Absolute
      volumes and calculated volume fractions (Vv) of tissue and subcellular components
      were assessed with quantitative stereologic morphometry. After ischemia the
      increase in volume of extracellular interstitium was inhibited by H290/51 (247 +/
      80 vs. 159 +/- 50 microl, mean +/- SD, groups A and B, respectively, p<0.05).
      The Vv (interstitium/myocard) was higher in control hearts (0.318 +/- 0.062 vs.
      0.206 +/- 0.067, p<0.05). Vv (cell edema/myocyte) was higher in the control group
      (0.144 +/- 0.07 vs. 0.083 +/- 0.033, p<0.05). Vv (myocyte/myocard) was higher in
      group B after ischemia than in the control group (0.622 +/- 0.071 vs. 0.707 +/-
      0.052, p<0.05). The decreased Vv (capillary/myocard) after ischemia was inhibited
      by H290/51. After reperfusion there was no difference between groups. Treatment
      with H290/51 reduced edema and ensured better preserved sarcolemmal membrane
      structure during ischemia. The effect was no longer present after reperfusion.

PMID- 11999803
TI  - Environmental induction models for the investigation of activity: changes in
      glutathione peroxidase, a crucial factor of the antioxidant defence.
AB  - Glutathione peroxidase enzyme superfamily plays significant role in the
      elimination of reactive oxygen free radicals in the animals. Many characteristics
      of these proteins have been revealed already, but their regulation is still not
      known. Several data suggest that some environmental factors have certain
      regulatory effect, while others propose strict genetic regulation. In this report
      we present four different environmental induction models in which New Zealand
      white rabbits were used as experimental animals. In three models, free radical
      load of different origin, lipidperoxide load, application of a glutathione
      depletor or a prooxidant agent, was introduced. Beside these negative models a
      positive model was also constructed in which additive selenium was supplied.
      Glutathione peroxidase activity was measured in blood serum, erythrocyte
      haemolysate and liver. Reduced glutathione, and malondialdehyde concentration in
      the liver were also determined. According to the results, the established models
      are capable for analysing the enzyme activity x environmental interactions.

PMID- 11999804
TI  - Binding capacity of rat liver glucocorticoid receptor in different periods after
      single neonatal benzpyrene treatment (imprinting).
AB  - Newborn rats of both sexes were treated (imprinted) with 20 microg of benzpyrene.
      Two hours, 2 days, 1, 2, 3 weeks, 1 month and 2 months after imprinting the liver
      glucocorticoid receptors were studied for binding of dexamethasone. Two-hour and
      2-day values were not appreciable. One week after treatment the receptor's
      affinity was extremely low both in control and treated treated animals. Two weeks
      after imprinting a significant difference in density (lower) and affinity
      (higher) was observed between the male treated and control animals. At 3 weeks
      and one month the binding capacity of treated and control animals was equal
      however, at 2 months Bmax of males increased and that of females decreased
      significantly in the neonatally benzpyrene treated animals. This means that for
      the development of perinatal imprinting effect a long time is needed, and the
      effect is manifested after a period of lability.

PMID- 11999805
TI  - Effect of tamoxifen treatment at adolescent age on the sexual behaviour and
      steroid hormone receptor binding of adult female rats.
AB  - Hormonal imprinting takes place perinatally, at the first encounter between the
      target hormone and its developing receptor. However, there is a secondary
      critical period of imprinting at puberty. In these periods molecules similar to
      the hormones (members of the same hormone family, antagonists, certain
      environmental pollutants, etc.) can cause faulty imprinting with lifelong
      consequences. In the present experiments 5+2 days of tamoxifen treatment (120
      microg/day) at adolescent age dramatically (from approx. 40% to 10%) reduced the
      sexual activity (Meyerson index and lordosis quotient) of female rats, soon after
      the finishment of the treatment and between four to six weeks after treatment.
      Similar results were observed in animals neonatally treated with allylestrenol
      and tamoxifen treated at puberty. Thymic glucocorticoid receptor and uterine
      estrogen receptor binding capacity were not influenced.

PMID- 11999806
TI  - Effects of zopiclone on blood glucose level, serum lipid concentration and clot
      lysis time in normoglycemic and normolipidemic rats.
AB  - In normoglycemic and normolipidemic rats the i.p. injection of zopiclone induced
      an acceleration of fibrinolysis in a dose-dependent bell shaped manner and
      various changes of the blood glucose level. Total lipids, total cholesterol and
      triglyceride serum levels remained unaffected by doses of 1.25, 2.5 and 15.0
      mg/kg, with the exception of the medium dose (5.0 mg/kg) and the next dose (10.0
      mg/kg) which lowered them very significantly.

PMID- 11999807
TI  - Immunohistochemical localization of epidermal growth factor receptor (EGF-R) in
      normal and diseased newborn lung tissues.
AB  - The distribution of EGF receptors (EGF-R) was examined in normal, hyaline
      membrane diseased and pneumonic newborn lung tissues by immunohistochemical
      methods under the light microscope. The PAP technique with polyclonal antibodies
      was performed to demonstrate the EGF receptor localisation in these tissues.
      Strong EGF-R reactivity was observed on bronchiolar epithelium and type I and
      type II alveolar cells in normal newborn lung tissues; whereas, poor reactivity
      was observed in alveolar macrophages. On the other hand, strong immunoreactivity
      was detected in type I alveolar cells and alveolar macrophages in hyaline
      membrane disease, but no reactivity was present in type II alveolar cells. The
      strongest immunoreactivity was observed in alveolar macrophages of newborn
      pneumonic lung tissues. In conclusion, the most meaningful form of reactivity was
      observed in normal newborn lung tissues of airway track and respiration area.
      This result is related with the maturation of the lungs after birth.

PMID- 11999808
TI  - Poetry, physiology, and puerperal fever: understanding the young Oliver Wendell
      Holmes.
AB  - The 19th-century American physician Oliver Wendell Holmes (1809-1894) is known,
      internationally, more for his literary output than for his contributions to
      medical science. Yet a single paper he wrote in 1843--"The Contagiousness of
      Puerperal Fever"--has made him a hero in the eyes of many (especially in the
      United States) of the struggle against that scourge. Why that one article,
      written when Holmes was still in his thirties, should--even in its expanded 1855
      version--so routinely be referred to as a "classic of medical literature", and
      why its author should have been raised on such a high pedestal that some grant
      him a position beside Ignac Semmelweis, are complicated questions. This present
      paper is an attempt to begin assessing what it is that makes someone a medical
      hero by looking at three different aspects of Holmes's early career. He was even
      as a young man a poet and a physiologist/anatomist as well as the author of this
      important essay. Whether and how those three features of Holmes's many-sides
      public persona are connected is discussed as a prelude to considering whether his
      work on puerperal fever legitimates his status as a medical hero.

PMID- 11999809
TI  - Prostanoid synthesis in the cerebral blood vessels of asphyxiated piglets.
AB  - The aim of this study was to examine the effects of asphyxia-reventilation and
      hyperoxia on the cerebral blood perfusion and prostanoid production of the brain
      arteries and microvessels in piglets. After 10 min of asphyxia, animals were
      ventilated with room air, or with 100% O2. Following 4 hours of recovery, the
      brains were perfused, cerebral arteries were removed and microvessels were
      isolated from the cortex. The microvessels and the arteries were incubated with 1
      14C-arachidonic acid, and the 1-14C-prostanoids were then separated by means of
      overpressure thin-layer chromatography and were quantitatively determined. Under
      control conditions, the synthesis of dilatory prostanoids dominated the
      arachidonate cascade both in the microvessels and in the arteries. Asphyxia and
      reventilation with room air did not modify the prostanoid production. O2
      ventilation greatly affected the prostanoid synthesis of the microvessels, with
      an enhancement of PGD2 up to 247 +/- 27%. In the arteries, the production of PGI2
      and of PGE2 was elevated to 272 +/- 15% and to 148 +/- 13%, respectively. These
      findings indicate that O2 ventilation after asphyxia substantially increases the
      extent of prostanoid synthesis in the cerebral blood vessels.

PMID- 11999810
TI  - Surgery of the abdominal aorta: experience of a university hospital in Thailand.
AB  - One hundred and thirty two patients who underwent aortic surgery at King
      Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 1991 to December
      2000 were studied. Twenty three patients (17.4%) were aged less than 60 years,
      102 (77.3%) aged 60-80 years, and 7 (5.3%) were older than 80 years. Ninety eight
      patients (74.2%) underwent elective operations and 34 (25.8%) underwent emergency
      operations. Elective abdominal aortic aneurysms (AAA) repair was the most common
      indication for abdominal aortic surgery (56.0%). Eighteen patients (13.6%)
      underwent surgery for infected AAA. The incidence of infected AAA was 16.1 per
      cent among patients with AAA. Fifteen patients (11.4%) had ruptured AAA and 19
      patients (14.4%) had aortoiliac occlusive disease. The overall mortality rate was
      15.2 per cent. The mortality of elective aortic surgery was 5.1 per cent and of
      emergency aortic surgery was 44.1 per cent. The mortality of elective AAA repair
      was 4 per cent. Multiple system organ failure was the most common cause of death
      (80%), followed by acute myocardial infarction (10%) and exsanguination (10%).
      The authors conclude that elective surgery on the abdominal aorta is safe and
      should be performed when indicated to prevent the development of complications
      requiring emergency surgery which carries a much higher risk.

PMID- 11999811
TI  - Laser bronchoscopy: experience at Siriraj Hospital.
AB  - Laser bronchoscopy is a major procedure employed in intervention bronchoscopy.
      From August 1998 to August 2000, 20 patients with endobronchial lesions were
      treated by this procedure in the Respiratory and Tuberculosis Division of the
      Department of Internal Medicine, Siriraj Hospital. Of 16 malignant lesion, a good
      response was obtained in 78 per cent (7 out of 9) of lesions in the proximal
      right main bronchus with failure to open any of the 3 completely obstructed
      lesions at the left distal bronchus. The results of treatment of malignant
      lesions in the trachea and carina were acceptable. Good results were obtained
      from all 4 benign endobronchial obstructions. No complications arose in this
      study. This small series demonstrates the benefit of laser bronchoscopy in
      patients with high risk endobronchial obstructive lesions.

PMID- 11999812
TI  - The Ramathibodi nasal filter in a simulated human airway: evaluated with laser
      smoke particles and a laser diode dust portable monitor.
AB  - The Ramathibodi nasal filter was specially designed as a personal respiratory
      protective device. It was attached to a simulated human airway composed of a
      nasal and pharyngeal model, airway passage and lung model machine. The system was
      run in a laser smoke particles environment. The laser smoke particles with
      suspended particulate matter size of less than 15, 10 and 2.5 microns (PM15, PM10
      and PM2.5) were selected. The amount of each particle size in the simulated human
      airway with and without the Ramathibodi nasal filter was measured continuously by
      a laser diode portable dust monitor. One hundred sample sizes were analyzed by a
      descriptive statistical method at the Department of Otolaryngology, Ramathibodi
      Hospital from January to November 1999. The graphic distribution patterns of each
      residual particle size in the simulated human airway with and without the
      Ramathibodi nasal filter were compared. The filtration efficacy of the
      Ramathibodi nasal filter should be tested further by this experimental model. The
      device could be applied intermittently in adult nasal vestibules.

PMID- 11999813
TI  - Environmental and travel factors related to leptospirosis in Thailand.
AB  - To identify potential environmental and travel factors related to leptospirosis,
      we conducted an unmatched case controlled study and household assessment of cases
      and controls in Nakhon Ratchasima province (north-eastern, Thailand) from August
      to December, 1998. Fifty-six cases and 145 controls were included in the study.
      Cases were hospitalized patients who had been diagnosed with leptospirosis and
      tested positive for anti-leptospiral IgM antibody using the Panbio ELISA (Panbio
      Inc, Brisbane, Australia). Controls were the neighbors of cases who had tested
      negative. Standardized questionnaires and household assessments were used to
      collect information on demographics, number of animals kept, evidence of rats in
      the home, presence of rat food inside the home, road characteristics, awareness
      of leptospirosis disease, environment, and travel history. Multivariant,
      unconditional logistic regression demonstrated that travel on potholed roads was
      independently associated with leptospirosis infection (OR 5.0; 95%CI 1.2-20.2)
      and traveling by car was a protective factor (OR 0.2; 95%CI 0.06-0.9).

PMID- 11999814
TI  - Prevalence of climacteric symptoms according to years after menopause.
AB  - OBJECTIVE: To study the prevalence of menopausal symptoms of women attending the
      menopause and gynecology clinics at Chulalongkorn Hospital. STUDY DESIGN: A
      descriptive study was conducted at the menopause and gynecology clinics at
      Chulalongkorn Hospital. After inclusion and exclusion were done, four hundred and
      twenty seven participants with premenopause, perimenopause and postmenopause were
      studied. All the women were classified into seven groups of premenopause,
      perimenopause and one, two, three, four and > or =five years after menopause. The
      interview was performed by well-trained social workers using standardized
      questionnaires. RESULTS: The average age at menopause of the postmenopausal women
      was 49.46 + 3.30 years. Prevalence of vasomotor symptoms eg. hot flushes in
      premenopause, perimenopause and one, two, three, four and > or =five years after
      menopause were 4.4 per cent, 25 per cent, 27.3 per cent, 38.8 per cent, 40 per
      cent, 11.1 per cent and 10.3 per cent, respectively. Prevalence of psychological
      symptoms eg. moodiness were 26.5 per cent, 25 per cent, 54.6 per cent, 38.7 per
      cent, 32.2 per cent, 11.2 per cent and 11.8 per cent, respectively. But the
      prevalence of headache in this category was 29.4 per cent, 23.3 per cent, 23.7
      per cent, 22.6 per cent, 25.0 per cent, 11.1 per cent and 13.2 per cent,
      respectively. Prevalence of urinary symptoms seemed to increase continuously
      after menopause. Prevalence of genital symptoms eg. vaginal dryness were 5.9 per
      cent, 13.3 per cent, 25.5 per cent, 25.8 per cent, 15.0 per cent, 16.7 per cent
      and 20.6 per cent, respectively. Prevalence of other symptoms eg. muscle and
      joint pain were 22.1 per cent, 43.3 per cent, 56.4 per cent, 58.0 per cent, 45.0
      per cent, 27.8 per cent and 28.0 per cent, respectively. CONCLUSION: The
      prevalence of menopausal symptoms in this postmenopausal group appeared to
      increase during the first and second years after menopause and tended to decrease
      afterwards. The prevalence of other symptoms eg. dry eyes and headache appeared
      to be unchanged after menopause.

PMID- 11999815
TI  - Three-dimensional conformal radiation therapy and periodic irradiation with the
      deep insipration breath-hold technique for hepatocellular carcinoma.
AB  - Nine cases of primary hepatocellular carcinoma were treated with 3D-conformal
      radiation therapy using computerized planning system. This technique permits the
      precise delivery of a high dose of radiation to the target while sparing most of
      the normal liver tissue. In order to decrease the effect of organ movement
      related to respiration, periodical irradiation was combined with the deep
      inspiration breath-hold technique. The radiation dose was equivalent to
      conventional radiation with a total dose of 50-70 Gy with 2 Gy, 5 times a week.
      Irradiation was given in 1-10 fractions which encompassed the target with 90 per
      cent isodose line. The patients tolerated the treatment procedure well without
      any complications inherent to the technique. The tumors were decreased in size,
      the pain symptom and abdominal discomfort were relieved for 3-20 months. This
      technique is an effective and safe treatment for palliation in hepatocellular
      carcinoma especially in locally advanced stages with large or multiple lesions.
      However, long term follow-up should be done to evaluate the late radiation effect
      and clinical outcome.

PMID- 11999816
TI  - Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin after
      coronary stent implantation: 1 and 6-month follow-up.
AB  - BACKGROUND: Clopidogrel is a new thienopyridine derivative and has less serious
      hematologic complications. We investigated the efficacy of clopidogrel plus
      aspirin (CA) in stent thrombosis prevention compared with ticlopidine plus
      aspirin (TA). METHOD AND RESULTS: Sixty-eight patients who underwent coronary
      stenting were randomized into 2 groups: TA group, n = 31 and CA group, n = 37. At
      1 month, there were 3 major bleeding complications, 2 in the CA group and 1 in
      the TA group. Neither stent thrombosis nor hematologic events were found in both
      groups. Two patients in the TA group died, 1 from sudden death and another from
      tracheal stenosis. At 6 months, five patients developed in-stent restenosis, 4 in
      the CA group and 1 in the TA group, p = NS. One patient in each group had acute
      coronary syndrome. CONCLUSION: Clopidogrel plus aspirin is an effective coronary
      stenting regimen comparable to ticlopidine plus aspirin.

PMID- 11999817
TI  - Anti-HIV-1 antibody testing using modified gelatin particle agglutination: a
      large field study.
AB  - Anti-HIV testing using gelatin particle agglutination (GPA) assay was
      investigated in parallel with ELISAs from routine service at Siriraj Hospital. In
      the first strategy, 174,032 sera from a patient population with an HIV-1
      seroprevalence of 13.72 per cent were assayed using reduced volumes of GPA
      reagents, giving a cost reduction of 40 per cent. In the second strategy, 90,560
      pregnant women and 48,936 emigrant workers with an HIV-1 seroprevalence of 2.2
      per cent and 0.3 per cent, respectively, were tested in pools of 4 sera using the
      manufacturer's recommended volumes, giving a cost saving of 67 per cent. Overall,
      the sensitivity and specificity were almost identical with standard methods.
      Thus, parallel use of either modified GPA might be considered appropriate when
      testing large numbers of samples. However, both modified versions of GPA are not
      recommended as the first assay for diagnostic or blood bank screening especially
      in high prevalence of HIV infection.

PMID- 11999818
TI  - Efficacy of octreotide in the control of acute upper gastrointestinal bleeding.
AB  - To evaluate the efficacy and safety of octreotide in the control of acute upper
      gastrointestinal (GI) bleeding and prevention of rebleeding, the Gastroenterology
      Unit, Chulalongkorn University Hospital, conducted a prospective open study in
      patients with acute upper GI bleeding. All patients with acute upper GI bleeding
      were given octreotide by intravenous infusion. The patients then had endoscopic
      confirmation within 24 hours, were divided into variceal and nonvariceal groups,
      and then randomly allocated to receive either 48 hours of octreotide infusion or
      48 hours of octreotide infusion plus 72 hours subcutaneous injection. Efficacy
      and safety of octreotide were evaluated during the 5 days observation period.
      Forty-three patients with acute upper GI bleeding were treated with octreotide
      infusion. After endoscopy, 16 patients in the variceal group and 22 patients in
      the non-variceal group were randomized to receive 48 hours infusion or 48 hours
      infusion plus 72 hours subcutaneous infusion. Failure to control active bleeding
      occurred in 11 patients (28.9%) and failure to prevent rebleeding was found in 5
      patients (13.2%). The results showed that the effect of octreotide infusion in
      controlling acute upper GI bleeding appeared to be not different between the
      variceal and non-variceal causes. Subcutaneous injection of octreotide for
      another 72 hours showed no apparent benefit for the prevention of rebleeding.

PMID- 11999819
TI  - Groin dressing after cardiac catheterization. Comparison between light dressing
      with thin transparent tape (Tegaderm) and conventional tight/pressure dressing
      with an elastic adhesive bandage (Tensoplast).
AB  - Post cardiac catheterization puncture site care is usually done with a tight
      pressure dressing by an elastic adhesive bandage (Tensoplast) due to the belief
      that it should prevent bleeding. The practice is uncomfortable to the patients.
      The authors compared a new way of dressing using light transparent tape
      (Tegaderm) to the conventional tight pressure one. 126 post coronary angiography
      patients were randomized to have their groins dressed either with Tensoplast or
      with Tegaderm. Patients ambulated 8 hours after the procedures. The groin was
      evaluated for pain, discomfort and bleeding complications. 49 per cent in the
      Tensoplast vs 26.9 per cent in the Tegaderm group experienced pain (p value of
      0.01). 55.5 per cent in the Tensoplast group vs 11.1 per cent in the Tegaderm
      group reported discomfort. 4.7 per cent in the Tensoplast vs 1.6 per cent in the
      Tegaderm group developed bleeding or hematoma. Dressing of the puncture site
      after cardiac catheterization with Tegaderm was more comfortable than the
      conventional Tensoplast without any difference in bleeding complications.

PMID- 11999820
TI  - Early neurological complications after stereotactic radiosurgery/radiotherapy.
AB  - OBJECTIVE: To evaluate the neurological complications after stereotactic
      radiosurgery (SRS) and stereotactic radiotherapy (SRT). MATERIAL AND METHOD: The
      Ramathibodi Radiosurgery Unit started its service in August 1997, using the
      linear-accelerator based system. There were 144 patients treated from August 1997
      to October 1999. Single fraction SRS was performed in 56 cases consisting of 46
      arteriovenous malformations (AVMs), 4 cranial nerve (CN) schwannomas, 3 pituitary
      adenomas, 2 meningiomas, and 1 multiple hemangioblastomas. Eighty eight patients
      received multifractionated SRT, including 27 meningiomas, 17 pituitary adenomas,
      13 benign and malignant gliomas, 8 brain metastasi(e)s, 5 CA nasopharynx, 5
      craniopharyngiomas, 5 CN schwannomas, 2 AVMs, 2 chordomas, and 4 others. After
      treatment the patients were clinically evaluated every 1-6 months and MRI was
      scheduled at 6 or 12-month interval or when there were abnormal clinical
      signs/symptoms. The complications included any new neurological complaints or
      findings during and after treatment. RESULTS: Median follow-up time was 9.5 (0
      20) months. Of 138 patients with available follow-up data, there were 23 (13 SRS
      and 10 SRT) cases who experienced new neurological symptoms at 3 weeks - 20
      months (median = 3 months) from the time treatment started. Symptoms included
      headache, seizure, weakness, decreased vision, vertigo with/without ataxia,
      diplopia, dizziness, impaired memory, hemifacial spasm, decreased sensation and
      facial palsy. Three AVM patients had intraventricular hemorrhage from the patent
      nidi. After symptomatic treatment there were 15 cases with complete recovery
      (including seizure control) and 6 with partial recovery. There were 2 deaths from
      ruptured AVM and progressive metastatic brain lesion. There were 79 patients who
      had at least 1 follow-up MRI, and changes were detected in T2-weighted images in
      19 cases at 3-18 months after treatment. Ten cases had symptoms corresponding to
      the image changes, the other 9 patients were asymptomatic. CONCLUSIONS: Longer
      follow-up time is needed to fully evaluate the complications after SRS/SRT,
      however, preliminary results showed that most of the complications were mild and
      transient. There was a tendency of a higher complication rate in the SRS group.
      Not all patients with post treatment image changes developed symptoms.

PMID- 11999821
TI  - Scrotal reconstruction using thigh pedicle flaps: long-term follow-up of 12
      cases.
AB  - INTRODUCTION: Genital skin loss in men may be caused by avulsion injuries of the
      penis and scrotum or by gangrene of the male genitalia. Reconstruction of the
      scrotum after complete loss of the overlying skin is a challenging problem. We
      report our experience on the management of this problem. MATERIAL AND METHOD:
      Medical records of all male patients with massive scrotal skin loss and exposed
      testes treated at Ramathibodi Hospital and Noparat Rajthanee Hospital from 1990
      to 1999 were reviewed. The etiologies of scrotal skin loss, technique of
      treatment, post-operative consequence as well as complications were noted.
      RESULTS: Twelve patients were described in this study. Nine patients had avulsion
      injuries of the penile and scrotal skin secondary to agricultural machinery
      accidents. Three patients were after extensive debridement of Fournierris
      gangrene. The exposed testes had been placed in thigh pouches and scrotal
      reconstruction using thigh pedicle flaps was done 4-6 weeks later. No immediate
      and delayed complications were detected in all of the patients. They recovered
      without any sequelae and had a satisfactory cosmetic result. CONCLUSION:
      Extensive scrotal skin loss should be immediately treated surgically.
      Implantation of the exposed testes in the upper thigh pouch and delayed
      reconstruction of the scrotum using thigh pedicle flaps can provide excellent
      results

PMID- 11999822
TI  - Misdiagnosis in vertebral osteomyelitis: problems and factors.
AB  - One hundred and one cases diagnosed with vertebral osteomyelitis were evaluated
      for misdiagnosis and both factors and outcomes of misdiagnosis were assessed.
      There were 67 patients with tuberculous spondylitis and 34 patients with pyogenic
      vertebral osteomyelitis. Misdiagnosis occurred in 33.7 per cent of the cases. The
      average delayed diagnosis time was 2.6 months (range, 0.2 to 12). Age between 60
      to 70 years was the most frequent group for misdiagnosis, while the most frequent
      area of misdiagnosis was the lumbar spine. Metastatic carcinoma, spinal stenosis,
      herniated nucleus palposus and back strain were common initial misdiagnoses. The
      factors, age group, absence of fever and positive straight leg raising test
      (SLRT) were associated with misdiagnosis in univariate analysis and multivariate
      analysis (odds ratio 3.40 (95%CI:1.07-11.94), 3.47 (95%CI:1.20-10.05), and 24.47
      (95%CI:2.18-274.28), respectively) Misdiagnosis was statistically significantly
      associated with the result of treatment. This paper emphasizes that the elderly
      age group, absence of fever and positive SLRT are the independent factors which
      increase the risk of misdiagnosis of vertebral osteomyelitis.

PMID- 11999823
TI  - Sigmoid colon perforation by ingested Sandorica seed.
AB  - This retrospective descriptive study of Sigmoid colon perforation by ingested
      Sandorica seed in patients who were admitted to Prachomklao Hospital from 1996 to
      2000. Nine cases were included in this study. Most cases were elderly with a mean
      age of 65 years (range 52-78 years). The main symptoms were abdominal pain with
      generalized peritonitis and severe tenderness at the suprapubic area, ileus and
      persistent vomiting. In all cases, the diagnosis was made at operation, with
      removal of the Sandorica seed, closure of the perforation at the rectosigmoid
      colon with simple suture and proximal transverse loop colostomy. Post-operative
      complications included two cases of wound infection.

PMID- 11999824
TI  - The role of diminished beta cell reserve and insulin resistance in secondary
      sulfonylurea failure of type 2 diabetes mellitus.
AB  - INTRODUCTION: The correction of hyperglycemia by insulin treatment has been shown
      to ameliorate beta cell function and insulin sensitivity in SU failure patients,
      and there also appears to have disparity between tests of beta cell function
      among these patients. The objectives of this study were to determine beta cell
      secretory reserve and insulin resistance of secondary SU failure type 2 diabetic
      patients who had fairly good glycemic control compared with those who were SU
      responsive and the disparity of beta cell responses to glucose and non-glucose
      stimuli were examined in these two groups. SUBJECTS AND METHOD: Eight secondary
      SU failure, insulin-treated and 11 SU responsive type 2 diabetic patients who
      were matched for age, degree of obesity, duration of diabetes as well as HbAlc
      were studied. Intravenous glucagon and oral glucose tolerance tests (OGTT) as
      well as short intravenous insulin tolerance test using arterialized venous blood
      were randomly performed on separate occasions to assess beta cell secretory
      reserve and insulin sensitivity, respectively. RESULTS: Basal (0.37+/-0.05 (SEM)
      vs 0.80+/-0.14 nmol/l; p=0.02) and stimulated c-peptide levels (0.66+0.08 vs
      1.16+/-0.14 nmol/l; p=0.007) after glucagon as well as basal (0.46+/-0.06 vs
      0.73+/-0.10 nmol/l; p=0.046) and maximal c-peptide responses (1.41+/-0.14 vs
      1.97+/-0.14 nmol/l; p=0.021) to glucose stimulation were significantly lower in
      SU failure than SU responsive patients. However, the incremental changes of c
      peptide over basal after glucagon (0.29+/-0.06 vs 0.37+/-0.09 nmol/l) and glucose
      (AUC: 36.9+/-7.6 vs 47.9+/-4.5 nmol/l/h) were not different between both groups.
      There were strong positive relationships between basal and stimulated c-peptide
      responses to glucagon (r=0.818; p=0.002) and glucose (r=0.85; p=0.001) in SU
      responsive patients but these relationships were not as strong in SU failure
      patients (r=0.682; p=0.062 and r=0.41; p=NS, respectively). Insulin sensitivity
      did not differ between the two groups. CONCLUSION: This study demonstrated that
      decreased basal, but not stimulated, insulin secretion was possibly a major
      factor associated with secondary SU failure in type 2 diabetic patients. With
      comparable glycemic control, there was no disparate beta cell responses to
      glucose and glucagon in patients with or without secondary SU failure.

PMID- 11999825
TI  - Bupropion for amphetamine withdrawal syndrome.
AB  - This study was a case report of an amphetamine abuser who came to see doctor
      because of amphetamine withdrawal syndrome three days after stopping prolonged
      use of amphetamine. The patient was treated him with a slow-release bupropion at
      the dose of 150 mg per day. After taking bupropion, his withdrawal symptoms i.e.
      dysphoric mood, fatigue, somnolence, and psychomotor retardation gradually
      disappeared within two to three days. Moreover, his craving for amphetamines was
      absent. The authors discussed the possible application for the clinical use for
      amphetamine abusers or dependence.

PMID- 11999826
TI  - A family at risk of congenital adrenal hyperplasia: a molecular approach for
      prenatal diagnosis.
AB  - The molecular method for prenatal diagnosis in the first trimester was carried
      out on the second and third pregnancies of a family at risk of congenital adrenal
      hyperplasia (CAH). The first child, an 8-year-old daughter, was affected. The
      molecular and cytogenetic prenatal diagnosis on the second pregnancy revealed
      that the fetus which was a female had been affected. The pregnancy was then
      terminated. The couple presented with the third pregnancy at 8 weeks' gestation.
      The same approach revealed that the fetus, a male, was affected. The couple opted
      for continuation of pregnancy which was on-going at the time of the manuscript
      preparation. To our knowledge, this is the first family in Thailand who had
      molecular approach for prenatal diagnosis of CAH. This approach allows early
      information about the fetal status of the disease and, together with the result
      of fetal gender, will help early decision making in pregnancy management.

PMID- 11999827
TI  - Dislodge of T-tube into the bronchus, an unusual complication of the Montgomery T
      tube: a case report.
AB  - Laryngotracheal stenosis is a sequel of laryngeal trauma. Many surgical
      techniques have been developed to correct this problem. Sometimes it requires a
      tracheal T-tube after the surgical correction. Here the authors report an unusual
      complication of tracheal T-tube and suggest a method for the management of this
      complication.

PMID- 11999828
TI  - Cereal genomics: ushering in a brave new world.

PMID- 11999829
TI  - Expanding the genetic map of maize with the intermated B73 x Mo17 (IBM)
      population.
AB  - The effects of intermating on recombination and the development of linkage maps
      were assessed in maize. Progeny derived from a common population (B73 x Mo17)
      before and after five generations of intermating were genotyped at the same set
      of 190 RFLP loci. Intermating resulted in nearly a four-fold increase in the
      genetic map distance and increased the potential for improved genetic resolution
      in 91% of the intervals evaluated. This mapping population and related
      information should connect research involving dense genetic maps, physical
      mapping, gene isolation, comparative genomics, analysis of quantitative trait
      loci and investigations of heterosis.

PMID- 11999830
TI  - A high-density genetic map of Sorghum bicolor (L.) Moench based on 2926 AFLP,
      RFLP and SSR markers.
AB  - Using AFLP technology and a recombinant inbred line population derived from the
      sorghum cross of BTx623 x IS3620C, a high-density genetic map of the sorghum
      genome was constructed. The 1713 cM map encompassed 2926 loci distributed on ten
      linkage groups; 2454 of those loci are AFLP products generated from either the
      EcoRI/MseI or PstI/MseI enzyme combinations. Among the non-AFLP markers, 136 are
      SSRs previously mapped in sorghum, and 203 are cDNA and genomic clones from rice,
      barley, oat, and maize. This latter group of markers has been mapped in various
      grass species and, as such, can serve as reference markers in comparative
      mapping. Of the nearly 3000 markers mapped, 692 comprised a LOD >3.0 framework
      map on which the remaining markers were placed with lower resolution (LOD <3.0).
      By comparing the map positions of the common grass markers in all sorghum maps
      reported to date, it was determined that these reference markers were essentially
      collinear in all published maps. Some clustering of the EcoRI/MseI AFLP markers
      was observed, possibly in centromeric regions. In general, however, the AFLP
      markers filled most of the gaps left by the RFLP/SSR markers demonstrating that
      AFLP technology is effective in providing excellent genome coverage. A web site,
      http://SorghumGenome.tamu.edu, has been created to provide all the necessary
      information to facilitate the use of this map and the 2590 PCR-based markers.
      Finally, we discuss how the information contained in this map is being integrated
      into a sorghum physical map for map-based gene isolation, comparative genome
      analysis, and as a source of sequence-ready clones for genome sequencing
      projects.

PMID- 11999831
TI  - Data mining for simple sequence repeats in expressed sequence tags from barley,
      maize, rice, sorghum and wheat.
AB  - Plant genomics projects involving model species and many agriculturally important
      crops are resulting in a rapidly increasing database of genomic and expressed DNA
      sequences. The publicly available collection of expressed sequence tags (ESTs)
      from several grass species can be used in the analysis of both structural and
      functional relationships in these genomes. We analyzed over 260000 EST sequences
      from five different cereals for their potential use in developing simple sequence
      repeat (SSR) markers. The frequency of SSR-containing ESTs (SSR-ESTs) in this
      collection varied from 1.5% for maize to 4.7% for rice. In addition, we
      identified several ESTs that are related to the SSR-ESTs by BLAST analysis. The
      SSR-ESTs and the related sequences were clustered within each species in order to
      reduce the redundancy and to produce a longer consensus sequence. The consensus
      and singleton sequences from each species were pooled and clustered to identify
      cross-species matches. Overall a reduction in the redundancy by 85% was observed
      when the resulting consensus and singleton sequences (3569) were compared to the
      total number of SSR-EST and related sequences analyzed (24 606). This information
      can be useful for the development of SSR markers that can amplify across the
      grass genera for comparative mapping and genetics. Functional analysis may reveal
      their role in plant metabolism and gene evolution.

PMID- 11999832
TI  - Analysis of simple sequence repeats (SSRs) in wild barley from the Fertile
      Crescent: associations with ecology, geography and flowering time.
AB  - Wild barley, Hordeum spontaneum C. Koch, is the progenitor of cultivated barley,
      Hordeum vulgare. The centre of diversity is in the Fertile Crescent of the Near
      East, where wild barley grows in a wide range of conditions (temperature, water
      availability, day length, etc.). The genetic diversity of 39 wild barley
      genotypes collected from Israel, Turkey and Iran was studied with 33 SSRs of
      known map location. Analysis of molecular variance (AMOVA) was performed to
      partition the genetic variation present within from the variation between the
      three countries of origin. Using classification tree analysis, two (or three)
      specific SSRs were identified which could correctly classify most of the wild
      barley genotypes according to country of origin. Associations of SSR variation
      with flowering time and adaptation to site-of-origin ecology and geography were
      investigated by two contrasting statistical approaches, linear regression based
      on SSR length variation and linear regression based on SSR allele class
      differences. A number of SSRs were significantly associated with flowering time
      under four different growing regimes (short days, long days, unvernalised and
      vernalised). Most of the associations observed could be accounted for by close
      linkage of the SSR loci to earliness per se genes. No associations were found
      with photoperiodic and vernalisation response genes known to control flowering in
      cultivated barley suggesting that different genetic factors may be active in wild
      barley. Novel genomic regions controlling flowering time in wild barley were
      detected on chromosomes 1HS, 2HL, 3HS and 4HS. Associations of SSRs with site-of
      origin ecological and geographic data were found primarily in genomic regions
      determining plant development. This study shows that the analyses of SSR
      variation by allele class and repeat length are complementary, and that some SSRs
      are not necessarily selectively neutral.

PMID- 11999833
TI  - Discovery and assay of single-nucleotide polymorphisms in barley (Hordeum
      vulgare).
AB  - The least ambiguous genetic markers are those based on completely characterized
      DNA sequence polymorphisms. Unfortunately, assaying allele states by allele
      sequencing is slow and cumbersome. The most desirable type of genetic marker
      would be unambiguous, inexpensive to assay and would be assayable singly or in
      parallel with hundreds of other markers (multiplexable). In this report we
      sequenced alleles at 54 barley (Hordeum vulgare ssp. vulgare) loci, 38 of which
      contained single-nucleotide polymorphisms (SNPs). Many of these 38 loci contained
      multiple polymorphisms, and a total of 112 polymorphisms were scored in five
      barley genotypes. The polymorphism data set was analyzed both by using the
      individual mutations as cladistic characters and by reducing data for each locus
      to haplotypes. We compared the informativeness of these two approaches by
      consensus tree construction and bootstrap analysis. Both approaches provided
      similar results. Since some of the loci sequenced contained insertion/deletion
      events and multiple point mutations, we thought that these multiple-mutated loci
      might represent old alleles that predated the divergence of barley from H.
      spontaneum. We evaluated sequences from a sample of H. spontaneum accessions from
      the Eastern Mediterranean, and observed similar alleles present in both
      cultivated barley and H. spontaneum, suggesting either multiple domestication
      events or multiple transfers of genes between barley and its wild ancestor.

PMID- 11999834
TI  - Monitoring large-scale changes in transcript abundance in drought- and salt
      stressed barley.
AB  - Responses to drought and salinity in barley (Hordeum vulgare L. cv. Tokak) were
      monitored by microarray hybridization of 1463 DNA elements derived from cDNA
      libraries of 6 and 10 h drought-stressed plants. Functional identities indicated
      that many cDNAs in these libraries were associated with drought stress. About 38%
      of the transcripts were novel and functionally unknown. Hybridization experiments
      were analyzed for drought- and salinity-regulated sequences, with significant
      changes defined as a deviation from the control exceeding 2.5-fold. Responses of
      transcripts showed stress-dependent expression patterns and time courses. Nearly
      15% of all transcripts were either up- or down-regulated under drought stress,
      while NaCl led to a change in 5% of the transcripts (24 h, 150 mM NaCl).
      Transcripts that showed significant up-regulation under drought stress are
      exemplified by jasmonate-responsive, metallothionein-like, late-embryogenesis
      abundant (LEA) and ABA-responsive proteins. Most drastic down-regulation in a
      category was observed for photosynthesis-related functions. Up-regulation under
      both drought and salt stress was restricted to ESTs for metallothionein-like and
      LEA proteins, while increases in ubiquitin-related transcripts characterized salt
      stress. A number of functionally unknown transcripts from cDNA libraries of
      drought-stressed plants showed up-regulation by drought but down-regulation by
      salt stress, documenting how precisely transcript profiles report different
      growth conditions and environments.

PMID- 11999835
TI  - QTL analysis of proteome and transcriptome variations for dissecting the genetic
      architecture of complex traits in maize.
AB  - In this review, we present some studies on genetic analysis of proteome and
      transcriptome variations, which exemplify new strategies for a better
      understanding of the molecular and genetic bases of complex traits. A large
      genetic variability was revealed at the proteome expression level, which raised
      the possibility to predict phenotypical performance on the basis of gene product
      variability. This approach yielded limited results, but could be re-newed by
      extensive identification of proteins now allowed by mass spectrometry. The
      dissection of the genetic basis of the variation of individual protein amounts
      proves very powerful to select 'candidate' proteins, physiologically relevant for
      a given phenotypical trait, as shown by a study on the effect of water stress in
      maize. In order to investigate factors of grain quality in maize, we selected a
      regulatory locus known to control the expression of several storage protein
      genes, Opaque-2, and investigated the relationships between variability in zein
      amount and composition and the molecular polymorphism at this locus. Moreover, a
      QTL analysis revealed that the variability in Opaque-2 transcript abundance was
      controlled by several polymorphic trans-acting regulators unlinked to the Opaque
      2 structural gene. Such genetic approaches should represent additional tools for
      physiological analysis of the huge amounts of data generated by transcritome and
      proteome projects.

PMID- 11999836
TI  - Statistical methods for QTL mapping in cereals.
AB  - This paper gives an overview of the statistical theory suitable for mapping
      quantitative trait loci in experimental populations derived from inbred parents,
      with a particular emphasis on methodology for cereal crops. The basic theory is
      described, and some new areas of statistical research appropriate for mapping in
      cereal crops are discussed.

PMID- 11999837
TI  - Toward positional cloning of Vgt1, a QTL controlling the transition from the
      vegetative to the reproductive phase in maize.
AB  - Vgt1 (Vegetative to generative transition 1) is a quantitative trait locus (QTL)
      for flowering time in maize (Zea mays L.). Vgt1 was initially mapped in a ca. 5
      cM interval on chromosome bin 8.05, using a set of near-isogenic lines (NILs) in
      the genetic background of the late dent line N28, with the earliness allele
      introgressed from the early variety Gaspe Flint. A new large mapping population
      was produced by crossing N28 and one early NIL with a ca. 6-cM long Gaspe Flint
      introgression at the Vgt1 region. Using PCR-based assays at markers flanking
      Vgt1, 69 segmental NILs homozygous for independent crossovers near the QTL were
      developed. When the NILs were tested in replicated field trials for days to
      pollen shed (DPS) and plant node number (ND), the QTL followed a Mendelian
      segregation. Using bulk segregant analysis and AFLP profiling, 17 AFLP markers
      linked to the QTL region were identified. Statistical analysis indicated a
      substantial coincidence of the effects of Vgt1 on both DPS and ND. Vgt1 was
      mapped at ca. 0.3 cM from an AFLP marker. As compared to DPS, the higher
      heritability of ND allowed for a more accurate assessment of the effects of Vgt1.
      The feasibility of the positional cloning of Vgt1 is discussed.

PMID- 11999838
TI  - Detection of grain protein content QTLs across environments in tetraploid wheats.
AB  - Grain protein content (GPC) is an important quality factor in both durum and
      bread wheats. GPC is considered to be a polygenic trait influenced by
      environmental factors and management practice. The objectives of this study were
      both to compare the quantitative trait loci (QTL) for GPC in a population of 65
      recombinant inbred lines of tetraploid wheats evaluated in three locations for
      several years (eight data sets), and to investigate the genetic relationship
      among GPC and grain yield. QTLs were determined based on the Messapia x
      dicoccoides linkage map which covers 217 linked loci on the 14 chromosomes with
      42 additional loci as yet unassigned to linkage groups. The map extends to 1352
      cM; the average distance between adjacent markers was 6.3 cM. Seven QTLs for GPC,
      located on the chromosome arms 4BS, 5AL, 6AS (two loci), 6BS, 7AS and 7BS, were
      detected that were significant in at least one environment at P<0.001 or in at
      least two environments at P<0.01. One QTL was significant in all but one
      environment, two were significant in four or five environments, and four were
      significant in two out of eight environments. Six out of seven protein content
      QTLs had pleiotropic effects or were associated to QTLs for grain yield and
      explained the negative correlation among GPC and yield components. The present
      results support the concept that studies conducted in a single environment are
      likely to underestimate the number of QTLs that can influence a trait and that
      the phenotypic data for a quantitative trait should be collected over a range of
      locations to identify putative QTLs and determine their phenotypic effects.

PMID- 11999839
TI  - Genetic dissection of a major Fusarium head blight QTL in tetraploid wheat.
AB  - The devastating effect of Fusarium head blight (FHB) caused by Fusarium
      graminearum has led to significant financial losses across the Upper Midwest of
      the USA. These losses have spurred the need for research in biological, chemical,
      and genetic control methods for this disease. To date, most of the research on
      FHB resistance has concentrated on hexaploid wheat (Triticum aestivum L.) lines
      originating from China. Other sources of resistance to FHB would be desirable.
      One other source of resistance for both hexaploid wheat and tetraploid durum
      wheat (T. turgidum L. var. durum) is the wild tetraploid, T. turgidum L. var.
      dicoccoides (T. dicoccoides). Previous analysis of the 'Langdon'-T. dicoccoides
      chromosome substitution lines, LDN(Dic), indicated that the chromosome 3A
      substitution line expresses moderate levels of resistance to FHB. LDN(Dic-3A)
      recombinant inbred chromosome lines (RICL) were used to generate a linkage map of
      chromosome 3A with 19 molecular markers spanning a distance of 155.2 cM. The
      individual RICL and controls were screened for their FHB phenotype in two
      greenhouse seasons. Analysis of 83 RICL identified a single major quantitative
      trait locus, Qfhs.ndsu-3AS, that explains 37% of the phenotypic or 55% of the
      genetic variation for FHB resistance. A microsatellite locus, Xgwm2, is tightly
      linked to the highest point of the QTL peak. A region of the LDN (Dic-3A)
      chromosome associated with the QTL for FHB resistance encompasses a 29.3 cM
      region from Xmwg14 to Xbcd828.

PMID- 11999840
TI  - Puroindolines: the molecular genetic basis of wheat grain hardness.
AB  - The variation in grain hardness is the single most important trait that
      determines end-use quality of wheat. Grain texture classification is based
      primarily on either the resistance of kernels to crushing or the particle size
      distribution of ground grain or flour. Recently, the molecular genetic basis of
      grain hardness has become known, and it is the focus of this review. The
      puroindoline proteins a and b form the molecular basis of wheat grain hardness or
      texture. When both puroindolines are in their 'functional' wild state, grain
      texture is soft. When either one of the puroindolines is absent or altered by
      mutation, then the result is hard texture. In the case of durum wheat which lacks
      puroindolines, the texture is very hard. Puroindolines represent the molecular
      genetic basis of the Hardness locus on chromosome 5DS and the soft (Ha) and hard
      (ha) alleles present in hexaploid bread wheat varieties. To date, seven discrete
      hardness alleles have been described for wheat. All involve puroindoline a or b
      and have been designated Pina-D1b and Pinb-D1b through Pinb-D1g. A direct role of
      a related protein, grain softness protein (as currently defined), in wheat grain
      texture has yet to be demonstrated.

PMID- 11999841
TI  - Chromosome regions and stress-related sequences involved in resistance to abiotic
      stress in Triticeae.
AB  - Drought, low temperature and salinity are the most important abiotic stress
      factors limiting crop productivity. A genomic map of major loci and QTLs
      affecting stress tolerance in Triticeae identified the crucial role of the group
      5 chromosomes, where the highest concentration of QTLs and major loci controlling
      plant's adaptation to the environment (heading date, frost and salt tolerance)
      has been found. In addition, a conserved region with a major role in drought
      tolerance has been localized to the group 7 chromosomes. Extensive molecular
      biological studies have led to the cloning of many stress-related genes and
      responsive elements. The expression of some stress-related genes was shown to be
      linked to stress-tolerant QTLs, suggesting that these genes may represent the
      molecular basis of stress tolerance. The development of suitable genetic tools
      will allow the role of stress-related sequences and their relationship with
      stress-tolerant loci to be established in the near future.

PMID- 11999842
TI  - Molecular genetics of heat tolerance and heat shock proteins in cereals.
AB  - Heat stress is common in most cereal-growing areas of the world. In this paper,
      we summarize the current knowledge on the molecular and genetic basis of
      thermotolerance in vegetative and reproductive tissues of cereals. Significance
      of heat stress response and expression of heat shock proteins (HSPs) in
      thermotolerance of cereal yield and quality is discussed. Major avenues for
      increasing thermotolerance in cereals via conventional breeding or genetic
      modification are outlined.

PMID- 11999843
TI  - Mapping QTLs associated with drought avoidance in upland rice grown in the
      Philippines and West Africa.
AB  - Localizing genes that contribute to drought avoidance in a quantitative way
      should enable the exploitation of these genes in breeding through marker-assisted
      selection, and may lead to the discovery of gene identity and function. Between
      110 and 176 F6 recombinant inbred lines from a mapping population derived from a
      cross of upland rice varieties Bala and Azucena have been evaluated for
      indicators of drought avoidance in sites in the Philippines and West Africa over
      two dry seasons. A molecular map with 102 RFLP, 34 AFLP and six microsatellite
      markers has been used to map (by composite interval mapping) quantitative trait
      loci (QTLs) for the visual scores of leaf rolling and leaf drying and leaf
      relative water content. QTLs were mapped for each site and across sites. A total
      of 17 regions were identified which contained QTLs with a LOD score greater than
      3.2. For leaf rolling, Bala was the parent contributing the majority of positive
      alleles whilst for the other traits, Bala and Azucena contributed more evenly.
      Six of the 17 regions influenced more than one trait, explaining the phenotypic
      correlations between traits that were observed. Three QTLs appeared to be
      specific to the Philippines experiments. One QTL had opposing effects in the
      Philippines and West Africa. QTLs for relative water content were detected on
      chromosome 8, congruent with an osmotic adjustment QTL identified in another
      population. Only three of the QTLs identified here have not been reliably
      identified in the two other populations that have been screened for drought
      avoidance. By using several populations assessed for drought avoidance in
      different sites, the distribution and utility of QTLs for drought avoidance in
      rice is being elucidated.

PMID- 11999844
TI  - Identification of QTLs for root characteristics in maize grown in hydroponics and
      analysis of their overlap with QTLs for grain yield in the field at two water
      regimes.
AB  - We investigated the overlap among quantitative trait loci (QTLs) in maize for
      seminal root traits measured in hydroponics with QTLs for grain yield under well
      watered (GY-WW) and water-stressed (GY-WS) field conditions as well as for a
      drought tolerance index (DTI) computed as GY-WS/GY-WW. In hydroponics, 11, 7, 9,
      and 10 QTLs were identified for primary root length (R1L), primary root diameter
      (R1D), primary root weight (R1W), and for the weight of the adventitious seminal
      roots (R2W), respectively. In the field, 7, 8, and 9 QTLs were identified for GY
      WW, GY-WS, and DTI, respectively. Despite the weak correlation of root traits in
      hydroponics with GY-WW, GY-WS, and DTI, a noticeable overlap between the
      corresponding QTLs was observed. QTLs for R2W most frequently and consistently
      overlapped with QTLs for GY-WW, GY-WS, and/or DTI. At four QTL regions, an
      increase in R2W was positively associated with GY-WW, GY-WS, and/or DTI. A 10 cM
      interval on chromosome 1 between PGAMCTA205 and php20644 showed the strongest
      effect on R1L, R1D, R2W, GY-WW, GY-WS, and DTI. These results indicate the
      feasibility of using hydroponics in maize to identify QTL regions controlling
      root traits at an early growth stage and also influencing GY in the field. A
      comparative analysis of the QTL regions herein identified with those described in
      previous studies investigating root traits in different maize populations
      revealed a number of QTLs in common.

PMID- 11999845
TI  - Mapping QTLs associated with drought resistance in sorghum (Sorghum bicolor L.
      Moench).
AB  - Drought is a major abiotic stress factor limiting crop production. Identification
      of genetic factors involved in plant responses to drought stress will provide a
      solid foundation to improve drought resistance. Sorghum is well adapted to hot
      dry environments and regarded as a model for studying drought resistance among
      the grasses. Significant progress in genome mapping of this crop has also been
      made. In sorghum, rapid premature leaf death generally occurs when water is
      limited during the grain filling period. Premature leaf senescence, in turn,
      leads to charcoal rot, stalk lodging, and significant yield loss. More than 80%
      of commercial sorghum hybrids in the United States are grown under non-irrigated
      conditions and although most of them have pre-flowering drought resistance, many
      do not have any significant post-flowering drought resistance. Stay-green is one
      form of drought resistance mechanism, which gives sorghum resistance to premature
      senescence under soil moisture stress during the post-flowering period.
      Quantitative trait locus (QTL) studies with recombinant inbred lines (RILs) and
      near-isogenic lines (NILs) identified several genomic regions associated with
      resistance to pre-flowering and post-flowering drought stress. We have identified
      four genomic regions associated with the stay-green trait using a RIL population
      developed from B35 x Tx7000. These four major stay-green QTLs were consistently
      identified in all field trials and accounted for 53.5% of the phenotypic
      variance. We review the progress in mapping stay-green QTLs as a component of
      drought resistance in sorghum. The molecular genetic dissection of the QTLs
      affecting stay-green will provide further opportunities to elucidate the
      underlying physiological mechanisms involved in drought resistance in sorghum and
      other grasses.

PMID- 11999846
TI  - Trends in comparative genetics and their potential impacts on wheat and barley
      research.
AB  - We review some general points about comparative mapping, the evolution of gene
      families and recent advances in the understanding of angiosperm phylogeny. These
      are considered in relation to studies of large-genome cereals, particularly
      barley (Hordeum vulgare) and wheat (Triticum aestivum), with reference to methods
      of gene isolation. The relative merits of direct map-based cloning in barley and
      wheat, utilization of the smaller genome of rice (Oryza sativa) and gene homology
      methods that utilize information from model species such as Arabidopsis thaliana
      are briefly discussed.

PMID- 11999847
TI  - Comparative genomic mapping between a 754 kb region flanking DREB1A in
      Arabidopsis thaliana and maize.
AB  - Comparative mapping between model plant species for which the complete genome
      sequence is known and crop species has been suggested as a new strategy for the
      isolation of agronomically valuable genes. In this study, we tested whether
      comparative mapping between Arabidopsis and maize of a small region (754 kb)
      surrounding the DREB1A gene in Arabidopsis could lead to the identification of an
      orthologous region in maize containing the DREB1A homologue. The genomic sequence
      information available for Arabidopsis allowed for the selection of conserved, low
      copy genes that were used for the identification of maize homologues in a large
      EST database. In total, 17 maize homologues were mapped. A second BLAST
      comparison of these genes to the recently completed Arabidopsis sequence revealed
      that 15 homologues are likely to be orthologous as the highest similarity score
      was obtained either with the original Arabidopsis gene or with a highly similar
      Arabidopsis gene localized on a duplication of the investigated region on
      chromosome 5. The map position of these genes showed a significant degree of
      orthology with the Arabidopsis region. Nevertheless, extensive duplications and
      rearrangements in the Arabidopsis and maize genomes as well as the evolutionary
      distance between Arabidopsis and maize make it unlikely that orthology and
      collinearity between these two species are sufficient to aid gene prediction and
      cloning in maize.

PMID- 11999848
TI  - Characterization of the aldehyde dehydrogenase gene families of Zea mays and
      Arabidopsis.
AB  - Cytoplasmic male sterility is a maternally transmitted inability to produce
      viable pollen. Male sterility occurs in Texas (T) cytoplasm maize as a
      consequence of the premature degeneration of the tapetal cell layer during
      microspore development. This sterility can be overcome by the combined action of
      two nuclear restorer genes, rf1 and rf2a. The rf2a gene encodes a mitochondrial
      aldehyde dehydrogenase (ALDH) that is capable of oxidizing a variety of
      aldehydes. Six additional ALDH genes were cloned from maize and Arabidopsis. In
      vivo complementation assays and in vitro enzyme analyses demonstrated that all
      six genes encode functional ALDHs. Some of these ALDHs are predicted to
      accumulate in the mitochondria, others in the cytosol. The intron/exon boundaries
      of these genes are highly conserved across maize and Arabidopsis and between
      mitochondrial and cytosolic ALDHs. Although animal, fungal, and plant genomes
      each encode both mitochondrial and cytosolic ALDHs, it appears that either the
      gene duplications that generated the mitochondrial and the cytosolic ALDHs
      occurred independently within each lineage or that homogenizing gene conversion
      like events have occurred independently within each lineage. All studied plant
      genomes contain two confirmed or predicted mitochondrial ALDHs. It appears that
      these mitochondrial ALDH genes arose via independent duplications after the
      divergence of monocots and dicots or that independent gene conversion-like events
      have homogenized the mitochondrial ALDH genes in the monocot and dicot lineages.
      A computation approach was used to identify amino acid residues likely to be
      responsible for functional differences between mitochondrial and cytosolic ALDHs.

PMID- 11999849
TI  - A high-density cytogenetic map of the Aegilops tauschii genome incorporating
      retrotransposons and defense-related genes: insights into cereal chromosome
      structure and function.
AB  - Aegilops tauschii (Coss.) Schmal. (2n = 2x = 14, DD) (syn. A. squarrosa L.;
      Triticum tauschii) is well known as the D-genome donor of bread wheat (T.
      aestivum, 2n = 6x = 42, AABBDD). Because of conserved synteny, a high-density map
      of the A. tauschii genome will be useful for breeding and genetics within the
      tribe Triticeae which besides bread wheat also includes barley and rye. We have
      placed 249 new loci onto a high-density integrated cytological and genetic map of
      A. tauschii for a total of 732 loci making it one of the most extensive maps
      produced to date for the Triticeae species. Of the mapped loci, 160 are defense
      related genes. The retrotransposon marker system recently developed for
      cultivated barley (Hordeum vulgare L.) was successfully applied to A. tauschii
      with the placement of 80 retrotransposon loci onto the map. A total of 50
      microsatellite and ISSR loci were also added. Most of the retrotransposon loci,
      resistance (R), and defense-response (DR) genes are organized into clusters:
      retrotransposon clusters in the pericentromeric regions, R and DR gene clusters
      in distal/telomeric regions. Markers are non-randomly distributed with low
      density in the pericentromeric regions and marker clusters in the distal regions.
      A significant correlation between the physical density of markers (number of
      markers mapped to the chromosome segment/physical length of the same segment in
      microm) and recombination rate (genetic length of a chromosome segment/physical
      length of the same segment in microm) was demonstrated. Discrete regions of
      negative or positive interference (an excess or deficiency of crossovers in
      adjacent intervals relative to the expected rates on the assumption of no
      interference) was observed in most of the chromosomes. Surprisingly,
      pericentromeric regions showed negative interference. Islands with negative,
      positive and/or no interference were present in interstitial and distal regions.
      Most of the positive interference was restricted to the long arms. The model of
      chromosome structure and function in cereals with large genomes that emerges from
      these studies is discussed.

PMID- 11999850
TI  - Structural and functional organization of the '1S0.8 gene-rich region' in the
      Triticeae.
AB  - Wheat genes are present in physically small, gene-rich regions, interspersed by
      gene-poor blocks of retrotransposon-like repetitive sequences. One of the largest
      gene-rich regions is present around fraction length (FL) 0.8 of the short arm of
      wheat homoeologous group 1 chromosomes and is called '1S0.8 region'. The
      objective of this study was to reveal the structural and functional organization
      of the '1S0.8 region' in various Triticeae and other Poaceae species. Consensus
      genetic linkage maps of the '1S0.8 region' were constructed for wheat, barley,
      and rye by combining mapping information from 16, 11, and 12 genetic linkage
      maps, respectively. The consensus genetic linkage maps were compared with each
      other and with a consensus physical map of wheat homoeologous group 1.
      Comparative analyses localized 75 agronomically important genes to the '1S0.8
      region'. This high-resolution comparison revealed exceptions to the rule of
      conserved gene synteny, established using low-resolution marker comparisons.
      Small rearrangements such as duplications, deletions, and inversions were
      observed among species. Proportion ofchromosomal recombination occurring in the
      '1S0.8 region' was very similar among species. Within the gene-rich region, the
      extent of recombination was highly variable but the pattern was similar among
      species. Relative recombination among markers was similar except for a few loci
      where drastic differences were observed among species. Chromosomal rearrangements
      did not always change the extent of recombination for the region. Differences in
      gene order and relative recombination were the least between wheat and barley,
      and were the highest between wheat and oat.

PMID- 11999851
TI  - Phylogenetic analysis of the acetyl-CoA carboxylase and 3-phosphoglycerate kinase
      loci in wheat and other grasses.
AB  - We have applied a two-gene system based on the sequences of nuclear genes
      encoding multi-domain plastid acetyl-CoA carboxylase (ACCase) and plastid 3
      phosphoglycerate kinase (PGK) to study grass evolution. Our analysis revealed
      that these genes are single-copy in most of the grass species studied, allowing
      the establishment of orthologous relationships between them. These relationships
      are consistent with the known facts of their evolution: the eukaryotic origin of
      the plastid ACCase, created by duplication of a gene encoding the cytosolic multi
      domain ACCase gene early in grass evolution, and the prokaryotic (endosymbiont)
      origin of the plastid PGK. The major phylogenetic relationships among grasses
      deduced from the nucleotide sequence comparisons of ACCase and PGK genes are
      consistent with each other and with the milestones of grass evolution revealed by
      other methods. Nucleotide substitution rates were calculated based on multiple
      pairwise sequence comparisons. On a relative basis, with the divergence of the
      Pooideae and Panicoideae subfamilies set at 60 million years ago (MYA), events
      leading to the Triticum/Aegilops complex occurred at the following intervals:
      divergence of Lolium (Lolium rigidum) at 35 MYA, divergence of Hordeum (Hordeum
      vulgare) at 11 MYA and divergence of Secale (Secale cereale) at 7 MYA. On the
      same scale, gene duplication leading to the multi-domain plastid ACCase in
      grasses occurred at 129 MYA, divergence of grass and dicot plastid PGK genes at
      137 MYA, and divergence of grass and dicot cytosolic PGK genes at 155 MYA. The
      ACCase and PGK genes provide a well-understood two-locus system to study grass
      phylogeny, evolution and systematics.

PMID- 11999852
TI  - Numerous small rearrangements of gene content, order and orientation
      differentiate grass genomes.
AB  - Comparative genetic mapping has indicated that the grass family (Poaceae)
      exhibits extensive chromosomal collinearity. In order to investigate
      microcollinearity in these genomes, several laboratories have begun to undertake
      comparative DNA sequence analyses of orthologous chromosome segments from various
      grass species. Five different regions have now been investigated in detail, with
      four regions sequenced for maize, rice and sorghum, plus two for wheat and one
      for barley. In all five of these segments, gene rearrangements were observed in
      at least one of the comparisons. Most of the detected rearrangements are small,
      involving the inversion, duplication, translocation or deletion of DNA segments
      that contain only 1-3 genes. Even closely related species, like barley and wheat
      or maize and sorghum, exhibit approximately 20% alterations in gene content or
      orientation. These results indicate that thousands of small genetic
      rearrangements have occurred in several grass lineages since their divergence
      from common ancestors. These rearrangements have largely been missed by genetic
      mapping and will both complicate and enrich the use of comparative genetics in
      the grasses.

PMID- 11999853
TI  - A measurement theory of illusory conjunctions.
AB  - Illusory conjunctions refer to the incorrect perceptual combination of correctly
      perceived features, such as color and shape. Research on the phenomenon has been
      hampered by the lack of a measurement theory that accounts for guessing features,
      as well as the incorrect combination of correctly perceived features. Recently,
      several investigators have suggested using multinomial models as a tool for
      measuring feature integration. The authors examined the adequacy of these models
      in 2 experiments by testing whether model parameters reflect changes in stimulus
      factors. In a third experiment, confidence ratings were used as a tool for
      testing the model. Multinomial models accurately reflected both variations in
      stimulus factors and observers' trial-by-trial confidence ratings.

PMID- 11999854
TI  - Influence of onset density on spoken-word recognition.
AB  - Previous research has suggested that the initial portion of a word activates
      similar sounding words that compete for recognition. Other research has shown
      that the number of similar sounding words that are activated influences the speed
      and accuracy of recognition. Words with few neighbors are processed more quickly
      and accurately than words with many neighbors. The influences of the number of
      lexical competitors in the initial part of the word were examined in a shadowing
      and a lexical-decision task. Target words with few neighbors that share the
      initial phoneme were responded to more quickly than target words with many
      neighbors that share the initial phoneme. The implications of onset-density
      effects for models of spoken-word recognition are discussed.

PMID- 11999855
TI  - The duality of selection: excitatory and inhibitory processes in auditory
      selective attention.
AB  - Behavioral and event-related potential (ERP) measurements were made in an
      auditory selective-attention paradigm, both before and after a series of
      inhibition or discrimination training sessions. The presence of distractors
      caused poor perceptual sensitivity, weak P3 responses, conservative responding,
      and slow reaction times relative to baseline. Distraction prompted a frontal
      enhancement of ERP components occurring 100-250 ms after the onset of attended
      signals (N1, P2, and N2). Training ameliorated behavioral interference from
      distraction. Participants receiving inhibition training acquired improved
      inhibitory processing of distractors, an effect that peaked 200 ms after
      distractor onset. In a proposed model, distinct excitatory and inhibitory
      mechanisms work interactively to maintain sensitivity to environmental change in
      the face of disruption from the contextual integration of irrelevant events.

PMID- 11999856
TI  - On the complexities of measuring naming.
AB  - The aims of this study were to investigate the adequacy of electronic voice keys
      for the purpose of measuring naming latency and to test the assumption that voice
      key error can be controlled by matching conditions on initial phoneme. Three
      types of naming latency measurements (hand-coding and 2 types of voice keys) were
      used to investigate effects of onset complexity (e.g., sat vs. spat) on reading
      aloud (J. R. Frederiksen & J. F. Kroll, 1976; A. H. Kawamoto & C. T. Kello,
      1999). The 3 measurement techniques produced the 3 logically possible results: a
      significant complexity advantage, a significant complexity disadvantage, and a
      null effect. Analyses of the performance of each voice key are carried out, and
      implications for studies of naming latency are discussed.

PMID- 11999857
TI  - Temporal integration between visual images and visual percepts.
AB  - Using a temporal integration task, subjects in 5 experiments were expected to
      combine information from temporally separated visual presentations. Evidence from
      these experiments indicated that perceptual information can be integrated with
      previously generated and currently maintained visual images to form a
      representation that contains information from each source. Properties and
      limitations of this integration process were also explored, including the time
      required to generated the image, the speed at which percepts were integrated with
      images, and the capacity of the representation. Implications for theories of
      visual processing and memory are discussed.

PMID- 11999858
TI  - Baseball outfielders maintain a linear optical trajectory when tracking
      uncatchable fly balls.
AB  - The authors investigated whether behavior of fielders pursuing uncatchable fly
      balls supported either (a) maintenance of a linear optical trajectory (LOT) with
      monotonic increases in optical ball height or (b) maintenance of optical
      acceleration cancellation (OAC) with simultaneous lateral alignment with the
      ball. Past work supports usage of both LOT and OAC strategies in the pursuit of
      catchable balls headed to the side. When balls are uncatchable, fielders must
      choose either optical linearity or alignment at the expense of the other.
      Fielders maintained the LOT strategy more often and for a longer period of time
      than they did the OAC alignment strategy. Findings support the LOT strategy as
      primary when pursuing balls headed to the side, whether catchable or not.

PMID- 11999859
TI  - Selective attention and the acquisition of new phonetic categories.
AB  - A class of selective attention models often applied to speech perception is used
      to study effects of training on the perception of an unfamiliar phonetic
      contrast. Attention-to-dimension (A2D) models of perceptual learning assume that
      the dimensions that structure listeners' perceptual space are constant and that
      learning involves only the reweighting of existing dimensions to emphasize or de
      emphasize different sensory dimensions. Multidimensional scaling is used to
      identify the acoustic-phonetic dimensions listeners use before and after training
      to recognize the 3 classes of Korean stop consonants. Results suggest that A2D
      models can account for some observed restructuring of listeners' perceptual
      space, but listeners also show evidence of directing attention to a previously
      unattended dimension of phonetic contrast.

PMID- 11999860
TI  - Change detection in multi-voice music: the role of musical structure, musical
      training, and task demands.
AB  - This study evaluated the relationship between primitive and scheme-driven
      grouping (A. S. Bregman, 1990) by comparing the ability of different listeners to
      detect single note changes in 3-voice musical compositions. Primitive grouping
      was manipulated by the use of 2 distinctly different compositional styles
      (homophony and polyphony). The effects of scheme-driven processes were tested by
      comparing performance of 2 groups of listeners (musicians and nonmusicians) and
      by varying task demands (integrative and selective listening). Following previous
      studies, which had tested only musically trained participants, several variables
      were manipulated within each compositional style. The results indicated that,
      although musicians demonstrated a higher sensitivity to changes than did
      nonmusicians, the 2 groups exhibited similar patterns of sensitivity under a
      variety of conditions.

PMID- 11999861
TI  - Visual marking and visual change.
AB  - Five experiments investigated the types of changes that disrupt the preview
      effect--the benefit gained in difficult search tasks from presenting some
      distractors earlier in time. A shape change with or without an overall luminance
      change at the location of an old item was found to disrupt the preview effect,
      whereas an equivalent luminance change alone or an isoluminant color change was
      not disruptive. Results suggest that (a) relatively low-level visual changes may
      not be sufficient to abolish the benefit, (b) the benefit most likely occurs
      through inhibition applied to locations within a location master map, and (c)
      inhibition need not be applied to surface features of objects.

PMID- 11999862
TI  - Ideomotor compatibility in the psychological refractory period effect: 29 years
      of oversimplification.
AB  - Four experiments examined whether the psychological refractory period (PRP)
      effect can be eliminated with ideomotor compatible (IM) but not stimulus-response
      compatible (SR) tasks, as reported by A. G. Greenwald and H. G. Shulman (1973).
      Their tasks were used: a left or right movement to a left- or right-pointing
      arrow (IM) or to the word left or right (SR) for Task 1; saying "A" or "B" (IM)
      or "1" or "2" (SR) to an auditory A or B for Task 2. The stimulus onset
      asynchronies were 0, 100, 200, 300, 500, and 1,000 ms in Experiment 1, and only
      0, 100, 200, and 1,000 ms in Experiments 2-4. The arrow was in the center of the
      screen in Experiments 1-3 and to the left or right in Experiment 4. As in
      Greenwald and Shulman's Experiment 2, the instructions stated that most often the
      2 stimuli would be presented simultaneously. A PRP effect was obtained in all
      conditions, most likely because response-selection decisions are required even
      for IM tasks.

PMID- 11999863
TI  - Automaticity and voluntary control of phase correction following event onset
      shifts in sensorimotor synchronization.
AB  - Seven experiments show that an event onset shift (EOS) in an auditory sequence
      causes an involuntary phase correction response (PCR) in synchronized finger
      tapping. This PCR is (a) equally large in inphase and antiphase tapping; (b)
      reduced but still present when the EOS occurs in either of two interleaved
      (target-distractor) sequences; (c) unaffected by increased pitch separation
      between these sequences; (d) asymptotic in magnitude as EOS magnitude increases,
      unlike the intentional PCR to expected phase shifts; and (e) enhanced when the
      EOS precedes the onset of tapping, because of phase resetting. Thus, phase
      correction is revealed to be partially automatic and partially under voluntary
      control, and to be based mainly on temporal information derived from simple onset
      detection.

PMID- 11999864
TI  - Unraveling mechanisms for expert object recognition: bridging brain activity and
      behavior.
AB  - Behavioral sensitivity to object transformations and the response to novel
      objects (Greebles) in the fusiform face area (FFA) was measured several times
      during expertise training. Sensitivity to 3 transformations increased with
      expertise: (a) configural changes in which halves of objects were misaligned, (b)
      configural changes in which some of the object parts were moved, and (c) the
      substitution of an object part with a part from a different object. The authors
      found that holistic-configural effects can arise from object representations that
      are differentiated in terms of features or parts. Moreover, a holistic-inclusive
      effect was correlated with changes in the right FFA. Face recognition may not be
      unique in its reliance on holistic processing, measured in terms of both behavior
      and brain activation.

PMID- 11999865
TI  - Visuomotor rotations of varying size and direction compete for a single internal
      model in motor working memory.
AB  - When participants adapt to equal and opposite visuomotor rotations in close
      temporal proximity, memory of the 1st is not consolidated. The authors
      investigated whether this retrograde interference depends on the use of equal and
      opposite rotations. On Day 1, different groups of participants adapted to a -30
      degrees rotation followed 5 min later by rotations of +30 degrees, +60 degrees,
      or -60 degrees. On Day 2, all groups were retested on the -30 degrees rotation.
      Either retrograde interference (in groups who adapted to rotations of opposite
      sign on Day 1) or retrograde facilitation (in the remaining group) was observed.
      In all groups, learning of the 2nd rotation resulted in unlearning of the first,
      indicating that all visuomotor rotations compete for common working memory
      resources.

PMID- 11999866
TI  - Limitations of object-based feature encoding in visual short-term memory.
AB  - The present study investigated object-based feature encoding in visual short-term
      memory for 2 features within the same dimension that occur on different parts of
      an object. Using the change-detection paradigm, this experiment studied objects
      with 2 colors and objects with 2 orientations. Participants found it easier to
      monitor 1 rather than both features of such objects, even when decision noise was
      properly controlled for. However, no object-based benefit was observed for
      encoding the 2 features of each object that were of the same dimension. When
      similar stimuli were used but the 2 features of each object were from different
      dimensions (color and orientation), an object-based benefit was observed. These
      results thus impose a major constraint on object-based feature encoding theories
      by showing that only features from different dimensions can benefit from object
      based encoding.

PMID- 11999867
TI  - The stereoscopic anisotropy: individual differences and underlying mechanisms.
AB  - Observers are more sensitive to variations in the depth of stereoscopic surfaces
      in a vertical than in a horizontal direction; however, there are large individual
      differences in this anisotropy. The authors measured discrimination thresholds
      for surfaces slanted about a vertical axis or inclined about a horizontal axis
      for 50 observers. Orientation and spatial frequency discrimination thresholds
      were also measured. For most observers, thresholds were lower for inclination
      than for slant and lower for orientation than for spatial frequency. There was a
      positive correlation between the 2 anisotropies, resulting from positive
      correlations between (a) orientation and inclination thresholds and (b) spatial
      frequency and slant thresholds. These results support the notion that surface
      inclination and slant perception is in part limited by the sensitivity of
      orientation and spatial frequency mechanisms.

PMID- 11999868
TI  - Repetition blindness has a perceptual locus: evidence from online processing of
      targets in RSVP streams.
AB  - Four experiments tested whether repetition blindness (RB; reduced accuracy
      reporting repetitions of briefly displayed items) is a perceptual or a memory
      recall phenomenon. RB was measured in rapid serial visual presentation (RSVP)
      streams, with the task altered to reduce memory demands. In Experiment 1 only the
      number of targets (1 vs. 2) was reported, eliminating the need to remember target
      identities. Experiment 2 segregated repeated and nonrepeated targets into
      separate blocks to reduce bias against repeated targets. Experiments 3 and 4
      required immediate "online" buttonpress responses to targets as they occurred.
      All 4 experiments showed very strong RB. Furthermore, the online response data
      showed clearly that the 2nd of the repeated targets is the one missed. The
      present results show that in the RSVP paradigm, RB occurs online during initial
      stimulus encoding and decision making. The authors argue that RB is indeed a
      perceptual phenomenon.

PMID- 11999869
TI  - Threat to ethnic identity: the experience of White Afrikaans-speaking
      participants in postapartheid South Africa.
AB  - The dismantling of apartheid and the postapartheid dispensation had far-reaching
      implications for all the citizens of South Africa. In an urban sample of White
      Afrikaans-speaking South Africans (Afrikaners) in postapartheid South Africa, the
      authors investigated perceptions of threat to ethnic identity, as well as
      correlates of those perceptions. The respondents experienced threat on 2 levels:
      The 1st was distinctive continuity, the concern that their ethnic group would not
      continue as a distinctive group in society. The 2nd was the evaluative dimension
      of ethnic identity (i.e., well-being), the concern that group membership would no
      longer contribute to positive self-esteem. The respondents experienced greater
      threat on the 2nd level, reflecting predominantly negative experiences as White
      Afrikaans-speaking persons in postapartheid South Africa. A high threat
      perception on the 2nd level was associated with (a) a perception of other groups'
      negative evaluations of their ethnic group, (b) negative attitudes toward
      political changes, and (c) perceptions of illegitimacy and instability of the
      postapartheid political system. The respondents who felt that Afrikaners would
      not continue as a distinctive group in society had a more positive attitude
      toward the sociopolitical changes, did not show strong ethnic identification, and
      had a negative collective self-esteem. They were also politically more liberal.
      Those findings are discussed in relation to theoretical expectations.

PMID- 11999870
TI  - Sequential requests and organ donation.
AB  - The author investigated the effectiveness of the foot-in-the-door technique as a
      method of increasing participants' intention to become organ donors. The
      participants who agreed to a 1st request were presented with a larger request
      either immediately or 3 days later. The 2nd request was presented either by the
      same requester or by a different requester. Compared with a control group
      receiving only the 2nd request, a significant foot-in-the-door effect emerged in
      all conditions except 1 (same requester-immediate request), in which the
      participants showed neither more nor less intention to become organ donors than
      did the control group.

PMID- 11999871
TI  - Acculturation attitudes, need for cognitive closure, and adaptation of
      immigrants.
AB  - The author validated Berry's model of acculturation (J. W. Berry, 1990a, 1990b,
      1991; J. W. Berry, U. Kim, S. Power, M. Young, & M. Bujaki, 1989) and examined
      the relation between acculturation attitudes and sociocultural and psychological
      adaptation among Croatian and Polish immigrants to Italy, 2 groups whose cultures
      are not very different from the Italian culture. Moreover, the author
      investigated the relation between the need for cognitive closure (NCC; M. D.
      Webster & A. W. Kruglanski, 1994) and psychological and sociocultural adaptation.
      The participants completed a questionnaire including measures of sociocultural
      adaptation, psychological adaptation, social relationships, acculturation
      attitudes, and NCC. The results of a multivariate analysis of variance revealed
      main effects of acculturation strategies for both forms of adaptation and a main
      effect of NCC for psychological adaptation. The Croatian and Polish immigrants
      differed in the level of sociocultural adaptation but not in the level of
      psychological adaptation.

PMID- 11999872
TI  - Social identification among political party voters and members: an empirical test
      of optimal distinctiveness theory.
AB  - According to optimal distinctiveness theory, minority political parties and
      parties of intermediate size provide more central and important bases of social
      identity. The authors tested that prediction in a sample of voters and a sample
      of political party members. In both samples, adherents of minority and
      intermediate parties did not perceive their parties to be more representative of
      them. The authors found no significant differences between political parties on
      the collective self-esteem questionnaire administered to the sample of political
      party members.

PMID- 11999873
TI  - Adaptive self-regulation: meeting others' expectations of leadership and
      performance.
AB  - The authors used longitudinal multisource field data to examine core aspects of
      the adaptive self-regulation model (A. S. Tsui & S. J. Ashford, 1994) in terms of
      linkages between self-monitoring, discrepancy in manager match-to-position, 5
      measures of leadership, and manager performance. At Time 1, 64 superiors of focal
      managers rated the managers' matches to their positions within the organization;
      at Time 3, they rated the managers' performance. At Time 2, the 64 focal managers
      completed a measure of self-monitoring, and 192 subordinates rated the focal
      managers' leadership behaviors. Results of partial least squares analysis
      revealed that discrepancy in manager match-to-position was associated with
      reductions in laissez faire and passive management-by-exception behaviors and
      increases in transformational leadership behavior. Self-monitoring was positively
      associated with all 5 leadership behaviors. Performance was related positively to
      transformational leadership behavior and negatively to passive management-by
      exception and contingent-reward behaviors

PMID- 11999874
TI  - Motives to study and socialization tactics among university students.
AB  - The authors focused on the period following students' admission to university and
      examined the effects of students' motives to study and socialization tactics on
      their academic achievement and academic satisfaction. The authors hypothesized
      that socialization tactics would mediate the relation of motives to study to
      academic achievement and satisfaction. The findings confirmed the hypotheses and
      highlighted the importance of students' socialization tactics in the university
      setting. In addition, the research provided a typology to distinguish different
      types of socialization tactics.

PMID- 11999875
TI  - General versus specific victim blaming.
AB  - The authors investigated (a) whether victim blaming is a general variable in a
      person's make-up or (b) whether the extent of blaming depends on the kind of
      victim considered. The authors evaluated scales for blaming (a) victims in
      general, (b) society in general, (c) a specific kind of victim (i.e., AIDS), and
      (d) the society in which AIDS victims live. The general and specific scales had
      favorable psychometric properties, including reliability. General and specific
      victim blaming were significantly and positively correlated, whereas victim
      blaming and society blaming were not significantly correlated. Multiple
      regression analyses provided evidence of construct validity for the scales. All
      blaming variables were significantly related in the hypothesized directions to
      social distance, social responsibility, and discrimination (regarding persons
      with AIDS). The general and specific scales made significant and unique
      contributions. Implications for attribution theory and research are specified.

PMID- 11999876
TI  - Application of the attribution-value model of prejudice to homosexuality.
AB  - According to the attribution-value model, prejudice toward a group stems from 2
      interrelated variables: attributions of controllability and cultural value. Thus,
      prejudice toward gay men and lesbians may stem from others' holding them
      responsible for their behaviors and perceiving negative cultural value regarding
      homosexuality. The author tested that model by using the issue of homosexuality.
      The participants were Turkish undergraduates who completed a homophobia scale and
      answered questions about the origins of homosexuality, cultural attitudes toward
      homosexuality, and their own gender and sexual preferences. In general, the
      participants were prejudiced against gay men and lesbians. As expected,
      attributions of controllability and negative cultural value regarding
      homosexuality operated jointly to explain 39% of the variation in homophobia. The
      participants who thought that homosexuality was controllable had more negative
      attitudes toward gay men and lesbians than did those who thought that
      homosexuality was uncontrollable. The female participants were more tolerant of
      homosexuality than were the male participants.

PMID- 11999877
TI  - Spectrum of conduction abnormalities associated with maternal anti-Ro antibodies.

PMID- 11999878
TI  - Systemic lupus erythematosus and cancer: associated or not?
AB  - The frequency of cancer in patients with SLE is between 2.5 and 13.8%. A
      literature review has identified nine full-length studies that estimated the
      overall risk of cancer in SLE patients compared with the general population. Five
      of them have not noted an increased risk for the development of overall cancers
      among SLE patients compared with the general population. One study identified a
      30% increased risk (SIR or 1.3) for occurrence of cancer among 1585 SLE patients
      followed over 10,807 patient-years. Taken together, it is controversial whether
      the risk of all cancers is increased in SLE patients compared with the general
      population. Increased risk of lymphatic malignancies has been shown in multiple
      large series of SLE patients, but SLE is not associated with an increased risk
      for the development of most of the solid tumors. Pathogenic mechanisms involved
      with the development of lymphoproliferative malignancies in association with SLE
      include a common etiologic agent for both diseases, environmental factors as the
      use of cytotoxic or immunosuppressive agents, genetic variables, and immunologic
      factors as immunoregulatory disturbances of the immune system.

PMID- 11999879
TI  - Spectrum and progression of conduction abnormalities in infants born to mothers
      with anti-SSA/Ro-SSB/La antibodies.
AB  - The classic cardiac manifestation of neonatal lupus is congenital heart block,
      attributed to antibody-mediated inflammation and subsequent fibrosis of the
      atrioventricular (AV) node. In considering the pathologic process of injury it
      may be that tissue damage results in a range of conduction abnormalities.
      Identification of less-advanced degrees of block or of fibrosis around the AV
      node without any conduction abnormality on EKG would support this pathologic
      model, and serve as a potential marker for treatment if the conduction defect
      could be shown to progress. To ascertain the spectrum of arrhythmias associated
      with maternal anti-SSA/Ro-SSB/La antibodies, records of all children enrolled in
      the Research Registry for Neonatal Lupus were reviewed. Of 187 children with
      congenital heart block whose mothers have anti-SSA/Ro-SSB/La antibodies, nine had
      a prolonged PR interval on EKG at birth, four of whom progressed to more advanced
      AV block. A child whose younger sibling had third degree block was diagnosed with
      first degree block at age 10 years at the time of surgery for a broken wrist. Two
      children diagnosed in utero with second degree block were treated with
      dexamethasone and reverted to normal sinus rhythm by birth, but ultimately
      progressed to third degree block. Four children had second degree block at birth:
      of these, two progressed to third degree block. Sinus bradycardia (< 100 bpm) was
      present in three (3.8%) of 78 fetuses for whom atrial rates were recorded by
      echocardiogram. Of 40 neonates for whom EKGs were available, the mean atrial rate
      was 137+/-20 bpm (range 75-200). These data have important research and clinical
      implications. In contrast to the AV node, permanent sinoatrial nodal involvement
      is not clinically apparent. Perhaps many fetuses sustain mild inflammation, but
      resolution is variable, as suggested by the presence of incomplete AV block.
      Since subsequent progression of less-advanced degrees of block can occur, an EKG
      should be performed on all infants born to mothers with anti-SSA/Ro-SSB/La
      antibodies.

PMID- 11999880
TI  - Differences by race, sex and age in the clinical and immunologic features of
      recently diagnosed systemic lupus erythematosus patients in the southeastern
      United States.
AB  - We examined the prevalence of clinical and immunologic features of systemic lupus
      erythematosus (SLE) by race, sex and age in a population-based study of 265 SLE
      patients. Patients fulfilled the American College of Rheumatology classification
      criteria. The median time between diagnosis and study enrollment was 13 months.
      The clinical and hematologic data were limited to occurrences up to 6 months
      after the diagnosis date, as documented in medical records. We used sera
      collected at study enrollment from 244 (92%) patients for serologic testing of
      autoantibodies. The associations between clinical and immunological features of
      SLE and age, sex and race were examined using logistic regression. The effect of
      each of these variables was examined adjusting for the other two demographic
      factors. Mean age at diagnosis was 6 years younger among African-Americans and
      other minorities compared with white patients (P < 0.01). Discoid lupus,
      proteinuria, anti-Sm and anti-RNP autoantibodies were more commonly seen in
      African-American patients, with odds ratios higher than 3.0. Photosensitivity and
      mucosal ulcers were noted less often in African-American patients. Proteinuria,
      leukopenia, lymphopenia and thrombocytopenia were approximately three times more
      common in men compared with women. The prevalence of oral or nasal ulcers and
      anti-DNA autoantibodies declined with age. The extent to which the differences we
      observed reflect genetic or environmental influences on the disease process
      should be investigated.

PMID- 11999881
TI  - Anti-adenosine deaminase antibodies in lupus erythematosus.
AB  - Adenosine deaminase (ADA) is an enzyme involved in purine metabolism and has a
      major role in the development and function of lymphoid cells. Congenital
      deficiency of ADA results in severe immunodeficiency. Patients with congenital
      ADA deficiency treated with polyethylene glycol-conjugated bovine ADA develop
      antibodies to ADA. This leads us to investigate the role of anti-ADA antibodies
      in patients with systemic rheumatic diseases. Commercially available ADA was used
      in ELISA and immunoblots for detection of anti-ADA antibodies. Four out of 100
      patients examined were positive for anti-ADA antibodies. Two of them had
      peripheral blood lymphopenia but the antibody levels did not appear to correlate
      with the lymphocyte counts. Immunoblotting revealed that the antibodies
      recognized a 40 kDa peptide of ADA, corresponding to ADA1, the major component of
      ADA. Affinity-purified antibodies were used to locate the distribution of ADA on
      Hep-2 cells and lymphocytes by indirect immunofluorescence. Anti-ADA antibodies
      gave a distinct nuclear speckled pattern on acetone-fixed cells. With viable cell
      immunofluorescence, anti-ADA antibodies also stained the cell surface of HEp-2
      cells and lymphocytes, indicating surface expression of ADA. The anti-ADA
      antibodies failed to gain access into the cytoplasm or nuclei when added to the
      cultures of HEp-2 cells. In summary, this is the first report of detection of
      anti-ADA1 autoantibody which is a new type of ANA with discrete, speckled nuclear
      staining, but which may not be associated with lymphopenia.

PMID- 11999882
TI  - Menstrual disturbances in patients with systemic lupus erythematosus without
      alkylating therapy: clinical, hormonal and therapeutic associations.
AB  - We have evaluated 36 consecutive systemic lupus erythematosus (SLE) female
      patients, age 18-39 years, without current or previous alkylating therapy, in
      order to determine the prevalence of the menstrual disturbances and their
      clinical, hormonal and therapeutic associations. Seventeen patients presented
      normal cycles, whereas menstrual alterations were observed in 19. Ovarian
      function was generally preserved in these groups. Sub-clinical thyroid disease
      (normal free T4 and elevated TSH) and slightly increased prolactin levels were
      detected in 8% of patients, with comparable frequencies in both groups.
      Similarly, the current use of azathioprine was not associated with menstrual
      disturbances. Percentages of prednisone current use (P = 0.3), mean dose (P =
      0.062), and percentages of patients on high doses (> or = 30 mg/day; P = 0.09)
      were comparable in patients with or without menstrual alterations. In contrast,
      the mean SLEDAI levels (P = 0.02) and the frequency of patients with SLEDAI > or
      = 8 (P = 0.008) were higher in patients with irregular cycles. Interestingly, 5/7
      (71%) of the patients with menstrual disturbances and a new significant flare
      (SLEDAI > or = 8) were evaluated before the introduction of high dose steroid,
      supporting the idea that disease activity is a major factor in menstrual
      disorders in SLE patients without alkylating therapy.

PMID- 11999883
TI  - Elevated IL-16 levels in patients with systemic lupus erythematosus are
      associated with disease severity but not with genetic susceptibility to lupus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      several immunological abnormalities. The pathogenic importance of T cells in this
      disease is well established. Interleukin-16 (IL-16) is a cytokine which is mainly
      produced by CD8+ T cells and induces chemotaxis of CD4+ T cells and monocytes. IL
      16 levels have been shown to be elevated in SLE patients in a cross-sectional
      study, but the mechanism is unknown. To explore whether the increased IL-16
      levels are associated with genetic background or the disease itself, we
      investigated the IL-16 level in healthy first-degree family members of SLE
      patients and SLE patients who were followed over time with regard to disease
      activity. We observed high IL-16 levels in SLE patients with severe disease
      compared to SLE patients with non-severe disease and healthy controls.
      Furthermore, IL-16 levels in first-degree relatives were not different from those
      in healthy controls. These results suggest that high IL-16 levels are associated
      with severity of SLE, but not with genetic susceptibility to SLE. Finally, we
      followed the disease activity of SLE patients over time, which showed significant
      correlation between the SLE disease activity index and IL-16, ESR and the
      complement components C3, C4 and CH50. In conclusion, these results implicate an
      association of IL-16 with SLE.

PMID- 11999884
TI  - Abdominal crisis in a young man with systemic lupus erythematosus.
AB  - Medium-sized artery aneurysms are rare in patients with systemic lupus
      erythematosus (SLE). We report on a 21-year-old Chinese man with SLE and
      secondary antiphospholipid syndrome (APS) who presented with acute abdominal pain
      due to a ruptured right hepatic artery aneurysm. He was also found to have
      aneurysms of the left hepatic artery and splenic artery on autopsy. There have
      been only eight cases of hepatic artery aneurysm and one case of splenic artery
      aneurysm associated with SLE in the English literature. Abdominal aneurysm must
      be suspected in SLE patients presenting with acute abdominal pain,
      haemoperitoneum or occult bleeding.

PMID- 11999885
TI  - Acute intermittent porphyria and systemic lupus erythematosus: report of a case
      and review of the literature.
AB  - The case of a Greek woman with acute intermittent porphyria (AIP) associated with
      systemic lupus erythematosus (SLE) is described and the literature on this
      association is reviewed. The coexistence of these two diseases may be determined
      by unknown mechanisms or could be fortuitous.

PMID- 11999886
TI  - Significance of magnetic resonance imaging in the diagnosis of nodular
      regenerative hyperplasia of the liver complicated with systemic lupus
      erythematosus: a case report and review of the literature.
AB  - Nodular regenerative hyperplasia of the liver (NRH), characterized by multiple
      hepatic nodules in the absence of fibrosis, is a rare but important complication
      of systemic lupus erythematosus (SLE) associated with non-cirrhotic portal
      hypertension. The diagnosis of NRH is based on the pathological examination, and
      radiological findings of NRH are poorly documented. We report a case of a 40-year
      old woman with SLE complicated with NRH. Sixteen years after diagnosis of SLE,
      esophageal varices were incidentally found and diagnosis of portal hypertension
      due to NRH was made by magnetic resonance imaging (MRI) and confirmed by needle
      liver biopsy. Although MRI showed the lesions as significant nodules, neither
      computed tomography nor ultrasonography could demonstrate the nodules. However,
      serial MRI showed significant enlargement of the nodules for 2 years Because NRH
      may lead to portal hypertension with life-threatening variceral haemorrhage in
      patients with SLE, MRI is a useful, non-invasive examination to screen the
      patients for its presence and follow-up. We reviewed the literature regarding NRH
      in SLE and discuss the management of the affected patients.

PMID- 11999887
TI  - Failure to detect antibodies to the second extracellular loop of the serotonin 5
      HT4 receptor in systemic lupus erythematosus and primary Sjogren's syndrome.

PMID- 11999888
TI  - Lupus and malignancy.

PMID- 11999889
TI  - Early drop-outs, late drop-outs and completers: differences in the continuation
      phase of a clinical trial.
AB  - OBJECTIVE: The purpose of this study was to assess the differences between early
      and late drop-outs and completers in the continuation phase of a clinical trial.
      METHODS: The authors studied 119 outpatients who were treatment responders in an
      8-week open trial with fluoxetine 20 mg/day, and who were then enrolled in a 26
      week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and
      cognitive behavior therapy (CBT). Patients were assessed using the Structured
      Clinical Interview for DSM-III-R--Axis I (SCID-Patient Edition), Hamilton
      Depression Rating Scale (HAMD-17) and the following self-rated scales: Beck
      Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety Sensitivity
      Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the 26-week
      continuation phase. We defined "early drop-outs" (EDs) as patients who dropped
      out either at or prior to Visit 2 (which was at 2 months into the 6-month
      continuation phase); those dropping out at Visit 3 or later were defined as "late
      drop-outs" (LDs) (ED < or = 2 months; LD >2 months). The Kruskal-Wallis and the
      Mann-Whitney U tests were used for data analysis. RESULTS: Of the 119 patients,
      83 were completers (mean age: 42.1+/-9.0 years; 46 [55%] women; age of onset of
      major depressive disorder [MDD] = 24.3+/-12.5 years), II were EDs (mean age: 38.1
      + 13.0 years: 4 [36%] women; age of onset of MDD = 22.0+/-11.1 years) and 25 were
      LDs (mean age: 35.2+/-10.4 years; 12 [48%] women; age of onset of MDD = 24.6+/
      11.6 years). LDs were significantly younger than completers (P<.01). There was no
      significant difference in age between EDs and LDs, nor between EDs and
      completers. EDs were more likely to have been depressed for a longer period of
      time compared to LDs (P< .05). EDs completers were depressed for a longer period
      of time compared to LDs (P< .05). CONCLUSIONS: Our data suggest that late drop
      outs are significantly younger than completers, although age is not a predictor
      between early drop-outs and late drop-outs. Further, early drop-outs are
      depressed for a longer duration compared to late drop-outs completers are
      depressed for a longer duration than late dropouts, and Early drop-outs have
      significantly more social impairment compared to completers. Our study identified
      some patient characteristics significantly associated with dropping out of a long
      term clinical trial.

PMID- 11999890
TI  - Motor-induced brain activation in cortical, subcortical and cerebellar regions in
      schizophrenic inpatients. A whole brain fMRI fingertapping study.
AB  - Motor symptoms including neurological soft signs have been found to be more
      prevalent in schizophrenic patients. In addition, catatonic symptoms and
      neuroleptic treatment as well may influence cortical and subcortical motor
      organization in schizophrenia. The results of previous neuroimaging studies
      exploring motor function in patients with schizophrenia are inhomogenous
      reporting on a decreased activity in cortical motor regions in some studies and
      normal activity in others. Using fMRI, we studied 40 subjects performing a
      unilateral self-paced fingertapping task. Analyzing a general linear model of
      four groups, we compared patients with schizophrenia according to DSM-IV treated
      with olanzapine (OL; 10) or haloperidol (HA; 10) to healthy controls (HC; 10) and
      untreated patients (UN; 10). Brainvoyager software was used for data analyzing.
      In all groups, the contralateral motor cortex was significantly activated.
      Significant activation of the ipsilateral cerebellum was found in the UN group,
      the control group and the OL group. The contralateral basal ganglia were
      activated in UN and in controls. Motor-induced cortical and subcortical brain
      activation in HC was significantly higher than in patients with schizophrenia. UN
      with schizophrenia showed a significant overactivation than the other groups. In
      conclusion, we revealed a diminished activation in the patient group treated with
      neuroleptic drugs. This study outlines the importance of further fMRI studies to
      investigate interindividual activation differences under different conditions
      especially focusing on basal ganglia.

PMID- 11999891
TI  - Diversity of glutamate dehydrogenase in human brain.
AB  - Three forms of glutamate dehydrogenase (GDH, EC 1.4.1.3) are purified from human
      brain tissue. Two of them, named GDH I (consisting of 58+/-1-kDa subunit) and GDH
      II (consisting of 56+/-1 -kDa subunit), are readily solubilized and the third
      one, GDH III (consisting of 56+/-1-kDa subunit), is a membrane-associated
      (particulate bound) isoform. Kinetic constants were determined for GDH III. These
      GDH forms were found to differ in hydrophobicity as indicated by different
      affinity to Phenyl-Sepharose. All three GDH forms showed microheterogeneity on
      two-dimensional (2-D) gel electrophoresis. Specific polyclonal antibodies, which
      enable to determine the levels of immunoreactivities of all the GDH forms in
      human brain extracts by enzyme-chemiluminescent amplified (ECL)-Western
      immunoblotting, were obtained.

PMID- 11999892
TI  - The use of concomitant medications in psychiatric inpatients treated with either
      olanzapine or other antipsychotic agents: a naturalistic study at a state
      psychiatric hospital.
AB  - Concomitant medications are frequently used in the treatment of resistant
      psychiatric conditions to augment the primary psychotropic agent or to ameliorate
      side effects. The present study evaluated the prescription of concomitant
      psychiatric medications for psychiatric inpatients that were prescribed either
      olanzapine at its first commercial availability or another first-line
      antipsychotic agent. Sixty-nine newly admitted patients (mainly with
      schizophrenia) who were prescribed either olanzapine (n = 35) or another first
      line antipsychotic agent (n = 34) were assessed (for the prescription of other
      concomitant psychotropic drugs) before (2-4 weeks prior to study) and following 8
      weeks of treatment (unless discharged sooner). The results indicate that
      significantly fewer olanzapine-treated subjects were prescribed anticholinergic
      agents as compared to those prescribed other first-line antipsychotic agents, and
      a similar trend was noted in the prescription of mood stabilizers as well.
      Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication
      compared to pre-olanzapine treatment period. Olanzapine-treated subjects used
      more anxiolytic agents compared to the control group in the early stages of
      treatment, probably due to the greater baseline severity of illness. These data
      suggest that olanzapine use is associated with less use of anticholinergic and
      mood-stabilizing agents as compared to older antipsychotic agents. These results
      also suggest that there is less need for PRN antipsychotic medication following
      olanzapine treatment. More severely ill subjects may require more anxiolytics
      during olanzapine initiation. The need for less anticholinergic and mood
      stabilizing agent use with olanzapine could lead to greater adherence to long
      term treatment and perhaps decreased cost (i.e. use of blood and organ system
      monitoring with mood stabilizers). At the end of treatment, olanzapine-treated
      subjects had statistically significantly lesser concomitant medicine usage
      compared to control subjects.

PMID- 11999893
TI  - Role of 5-hT2C receptors in the hypophagic effect of m-CPP, ORG 37684 and CP
      94,253 in the rat.
AB  - Compounds that stimulate 5-HT2C and/or 5-HT1B receptors induce hypophagia, but
      the relative role of these receptors in the control of feeding behaviour remains
      to be unequivocally demonstrated. The objectives of the present study were: (a)
      comparison of the hypophagic effect of the mixed 5-HT2C/1B receptor agonist, m
      CPP, with that of ORG 37684 and CP-94,253, a relatively selective 5-HT2C and 5
      HT1B receptor agonist, respectively; (b) verification of the contribution of 5
      HT2C receptors to the hypophagic effect of these compounds by antagonism
      experiments; and (c) to test whether cotreatment with ORG 37684 and CP-94,253
      leads to a more pronounced reduction of food intake as compared with treatment
      with either compound alone. Food intake was measured in a free feeding
      experimental protocol employing female Wistar rats. m-CPP was more potent in
      suppressing food intake than ORG 37684 and CP-94,253 (ED50 values for the first
      hour of access: 0.45, 1.84 and 3.48 mg/kg ip, respectively). The 5-HT2C receptor
      antagonists, metergoline and SB 242.084, completely reversed the hypophagic
      effect of ORG 37684, but not that of CP-94,253 and m-CPP. The hypophagic effect
      of ORG 37684 was potentiated by a low (inactive) dose of CP-94,253 (ED50: 4.95
      and 2.44 mg/kg ip after vehicle and CP-94,253 pretreatment, respectively) and
      vice versa (ED50 values: 4.02 and 0.62 mg/kg ip). It is concluded that the
      hypophagic effect of ORG 37684-but not that of m-CPP and CP-94,253--is
      exclusively mediated by activation of 5-HT2C receptors. The results further
      indicate that simultaneous activation of 5-HT2C and 5-HT1B receptors underlies
      the higher potency of m-CPP in reducing food intake, as compared with other, more
      selective, compounds.

PMID- 11999894
TI  - Neuropsychiatric aspects of HIV disease progression: impact of traditional herbs
      on adult patients in Zimbabwe.
AB  - This cohort study examined the impact of phytotherapy (PT; traditional herbs) on
      neuropsychiatric aspects of HIV disease progression to antibody immunodeficiency
      syndrome (AIDS), CD4 counts, and viral load in adult patients in Harare,
      Zimbabwe. This is a community-based and nonintervention cohort study. The study
      was conducted in and around Harare City from June 1996 to May 1998. One hundred
      and five volunteers participated in the study. They were seen at the baseline and
      then followed up on a 3-month basis. The volunteers were interviewed, underwent
      physical examinations, and had blood drawn for laboratory tests, including the
      chest X-rays. The outcome measures were: prevalence of mental disorders and
      depressive symptoms, diagnosis of AIDS, and changes in CD4 cell counts and plasma
      HIV-I RNA concentrations. Instruments used were the Brief Psychiatric Rating
      Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), Structured
      Interview Diagnosis of Dementia According to the DSM-IV (SIDAM), and Centre for
      Disease Control and Prevention (CDC) criteria as measurement tools. The findings
      were that patients on the PT had a mean (S.D.) age of 34.5 (7.4) years, whereas
      those on conventional therapy were a bit older with a mean (S.D.) age of 36.4
      (6.6) years, range 19-55 years. The overall prevalence of psychiatric disorders
      according to the DSM-IV diagnostic criteria at the baseline was 44.8% (n=47, 95%
      CI=35.3-54.3) and by the end of the 6 months follow-up was 36% (n = 18, 95% CI =
      23-49). The relative risks of psychiatric diagnoses were less in patients on PT
      (P = .046), including the diagnoses of depression (P = .035), than those on
      conventional therapy. Mean levels of a reported symptom of suicidal thoughts
      according to the MADRS were lowest in patients on PT than those on conventional
      therapy (F=5.44, P=.022). Finally, PT is protective against psychiatric disorders
      in our patients. However, our findings did not support HIV-I disease progression
      to AIDS in these patients.

PMID- 11999895
TI  - No association of the MAOA gene with alcoholism among Han Chinese males in
      Taiwan.
AB  - A positive association of MAOA polymorphisms with alcoholism has been
      demonstrated in certain recent studies, however, this association is not
      universally supported. The haplotype status of the MAOA gene polymorphisms could
      provide more information than alleles at a single site alone tested for an
      association with a complex, heterogeous disorder. This study examines whether
      there is an association between alcoholism and either a variable number of tandem
      repeat located upstream of the MAOA gene or an EcoRV functional polymorphism of
      the MAOA gene. These are analyzed both individually and as haplotypes. The study
      consisted of 214 subjects meeting DSM-IV criteria for alcoholism from northern
      Taiwan and 77 control individuals without history of alcoholism from Taipei. All
      of the subjects were Chinese Han males. For the two polymorphic sites,
      significant linkage disequilibrium occurred. No significant intergroup difference
      was observed between the two subject groups with respect to the allele
      frequencies for the two polymorphisms at the MAO locus tested both individually
      and as haplotypes. This finding suggests that no association exists between
      genetic variation at the MAOA locus and alcoholism in Chinese Han males.

PMID- 11999896
TI  - 5-HT3 receptor ligands lack discriminative stimulus properties.
AB  - The putative discriminative stimulus of the 5-HT3 receptor antagonists
      ondansetron and (DL)-11-[(2-methyl-1H-imidazol-1-yl)methyl]-4,5,6,7,10,11,12
      octahydroazepinol[3,2,1-jk]-carbazol-12-one hydrochloride (DU122932), and of the
      5-HT3 receptor agonists 2-methyl-5-HT and 3,4-dichlorophenylbiguanide (3,4DCPB)
      were investigated in a standard two-lever, food-reinforced drug-saline
      discrimination procedure with groups of rats (N= 10 per group). In three groups
      of rats after 80 sessions with training doses ranging from 0.1 to 4.0 mg/kg po,
      stimulus control by ondansetron, DU122932 and 2-methyl-5-HT was still absent. The
      same 30 animals thereafter rapidly learned to discriminate chlordiazepoxide (CDP)
      from vehicle. In three other groups of rats, stimulus control by CDP was first
      established. Then, the vehicle was gradually (from 0.1 to 2.0 mg/kg po) replaced
      by either ondansetron, DU122932 or 2-methyl-5-HT. Finally, the dose of CDP was
      gradually decreased. In all three groups, stimulus control disappeared. A seventh
      group was trained to discriminate 3,4DCPB (5.0 mg/kg po) from saline. When
      training was not successful, dose and route were changed but discrimination was
      not attained. It is concluded that in the rat, using the classical two lever
      discrimination procedure, the 5-HT3 receptor ligands ondansetron, DU122932, 2
      methyl-5-HT and 3,4DCPB are incapable of producing an internal state that can act
      as a stimulus to control responding.

PMID- 11999897
TI  - Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic
      patients: influence of patient-related variables.
AB  - Steady-state plasma concentrations of clozapine and norclozapine, its major
      metabolite, as well as their sum and ratio (norclozapine/clozapine), were
      evaluated in 50 in- and outpatients taking clozapine and naturalistically
      recruited. Drug plasma concentrations were measured by means of a reversed-phase
      high-performance liquid chromatography (RPLC) method with an ultraviolet
      detection. Daily doses (milligrams per kilogram of body weight) of clozapine
      correlated positively with clozapine plasma parameters, except with the
      norclozapine/clozapine ratio, in all patients. When the patients were divided in
      subgroups with respect to gender, the corresponding plasma concentrations were no
      longer dose-related in men. A lack of significant correlation was observed also
      in patients (n=23) co-treated with typical neuroleptics. Conversely, dose
      concentration correlations were significant in either smoker or nonsmoker
      patients. No significant relationship between body weight and clozapine plasma
      parameters was reported. Further, we observed (1) a trend towards higher medians
      of clozapine or total analytes in women than those reported in men (P=.09 and
      .07); (2) no significant difference in plasma levels obtained in subjects younger
      than 34 years and subjects 34 years old or older; (3) a trend towards higher
      norclozapine and clozapine plus norclozapine levels (P=.05 and .08) in nonsmoker
      than smoker patients; (4) no significant difference between clozapine plasma
      parameters measured in patients co-medicated with typical neuroleptics and in
      patients receiving clozapine alone.

PMID- 11999898
TI  - Regional cerebral blood flow in deficit/nondeficit types of schizophrenia
      according to SDS criteria.
AB  - A relationship between "hypofrontality" and a negative form of schizophrenia is
      commonly found. The Schedule for the Deficit Syndrome (SDS) provides specific
      criteria for assessing the presence of negative symptoms, their duration and
      whether the symptoms are primary or secondary. The purpose of our study was to
      compare the regional cerebral blood flow (rCBF) at rest, in 62 deficit and
      nondeficit schizophrenic patients, according to the SDS criteria (French
      version). The deficit patients in our population were comparable to those
      described in the literature (stability of their negative symptoms with time, poor
      premorbid adjustment, duration of the illness, age at the first episode, etc.).
      No difference was found in the locoregional perfusion with respect to the DSM-III
      R type of schizophrenia, the sex or the type of treatment received. The patients
      with a deficit form of schizophrenia showed a significant bilateral reduction in
      single photon emission computed tomography (SPECT) perfusion in the right
      frontodorsolateral cortex (P=.0105) and the left frontodorsolateral cortex
      (P=.0004) compared with the nondeficit schizophrenic patients. The contribution
      of SDS seems to be helpful in distinguishing between significant cerebral
      characteristics in deficit schizophrenics, as defined by Carpenter. These results
      suggest a decrease in prefrontal perfusion at rest, which corresponds with
      neuropsychological data.

PMID- 11999899
TI  - Behavioral effects of MK-801 on reserpine-treated mice.
AB  - The effects of dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA)
      receptor antagonist, were studied on dopamine-related behaviors induced by
      reserpine treatments. This study focuses on behavioral syndromes that may used as
      models for Parkinson's disease, or tardive dyskinesia, and its response after
      glutamatergic blockage. Reserpine (1 mg/kg), administered once every other day
      for 4 days, produced increases in orofacial dyskinesia, tongue protrusion and
      vacuous chewing in mice, which are signs indicative of tardive dyskinesia.
      Reserpine also produced tremor and catalepsy, which are signs suggestive of
      Parkinson's disease. MK-801 (0.1 mg/kg), administered 30 min before the
      observation test, prevented the vacuous chewing movements, tongue protrusions and
      catalepsy induced by reserpine. However, MK-801 injection produced a significant
      increase of tremor in reserpine-treated mice. Reserpine (1 mg/kg), administered
      90 min before the test and followed by apomophine injection (0.1 mg/kg) 5 min
      before the test, did not produce oral dyskinesia in mice. On the other hand,
      reserpine induced increases in tremor and catalepsy compared to control mice. MK
      801 (0.1 mg/kg) administration attenuated the catalepsy and tremor induced by
      reserpine. Pretreatment with reserpine (1 mg/kg) 24 h before the observation test
      produced increases in vacuous chewing movements and tongue protrusion, as well as
      increases in tremor and catalepsy, whereas MK-801 (0.1 mg/kg) injection 90 min
      before the test reversed the effects of reserpine. These results show that
      reserpine produces different and abnormal movements, which are related to dose
      and schedule employed and can be considered as parkinsonian-like and tardive
      dsykinesia signs. The glutamatergic blockage produced by NMDA can restore these
      signs, such as vacuous chewing movements, tongue protrusions, catalepsy and
      tremor according to the employed model.

PMID- 11999900
TI  - Differential effects of the CCKA receptor ligands PD-140,548 and A-71623 on
      latent inhibition in the rat.
AB  - Latent inhibition (LI) is a behavioural paradigm in which repeated exposure to a
      stimulus without consequence inhibits the formation of any new associations with
      that stimulus. To the extent that LI reflects a process of leaming to ignore
      irrelevant stimuli, disrupted LI has been suggested as an animal model for the
      attentional deficits observed in schizophrenia. The antipsychotic potential of
      cholecystokinin (CCK) stems from its colocalization with dopamine (DA) in the
      mesolimbic pathway, where it demonstrates both excitatory and inhibitory effects
      on dopaminergic activity. This may be explained by mediation through different
      receptor subtypes. A variety of hypotheses has emerged regarding the potential
      clinical application of subtype-selective CCK-based drugs. The present
      experiments examined the effects on LI of two selective CCK(A) ligands: PD
      140,548 (a CCK(A) antagonist, Experiment 1: 0.001, 0.01, and 0.1 mg/kg) and A
      71623 (a CCK(A) agonist, Experiment 2: 0.02, 0.05, and 0.1 mg/kg). In both
      experiments, the effects of haloperidol (0.1 mg/kg) were also investigated.
      Animals receiving 0.1 mg/kg of haloperidol or 0.001 or 0.1 mg/kg (but not 0.01
      mg/kg) of PD-140,548 treated the preexposed stimulus as irrelevant after a low
      number of preexposures. In contrast, no facilitatory effect on LI was detectable
      at any of the A-71623 doses. The finding that A-71623 failed to enhance LI
      indicates that it is unlikely that this compound would have any antipsychotic
      effect within the clinical setting. Considering the facilitatory effect exerted
      by PD-140,548 on LI, it is probable that the inhibition of CCK activity might
      prove a more promising strategy for the pharmacological treatment of
      schizophrenia.

PMID- 11999901
TI  - Delayed onset of inhibition of return in schizophrenia.
AB  - Peripheral visual cues occuring before a subsequent target result in an almost
      immediate facilitatory and then a later inhibitory effect on target detection. In
      a detailed parametric investigation, the authors compared schizophrenic subjects
      (SCZ) and control subjects (CONT) to examine whether they showed any differences
      in the time course of these nonpredictive peripheral cuing effects. Subjects
      fixated a central position and made saccadic responses to visual targets. Targets
      were presented 10 degrees to the left or right of fixation and were preceded at
      various time intervals by visual cues. Targets occurred with equal probability in
      either the same position as the cue or in the opposite, uncued location, and 10
      delay periods were used corresponding to stimulus onset asynchronies (SOAs) of
      66, 79, 106, 133, 159, 226, 305, 505, 705, and 1000 ms. All subjects showed
      facilitation for short cue-target delays and inhibition of return (IOR) for
      longer delays. SCZ, however, showed an apparent shift in the time course of cuing
      effects in the form of a delayed onset of IOR. Using a task of reflexive
      orienting, these results support findings of a delayed rather than an absent
      inhibitory process in medicated SCZ.

PMID- 11999902
TI  - Effects of MK-801 and electroconvulsive shock on c-Fos expression in the rat
      hippocampus and frontal cortex.
AB  - Both the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and
      electroconvulsive shock (ECS) have been reported to induce c-Fos in rat brain.
      However, the former has anticonvulsant and psychotomimetic effects and the latter
      has proconvulsant and antipsychotic effects. To understand the mode of action of
      these treatments, the authors examined the effect of MK-801 and the interaction
      between MK-801 and ECS on the induction of c-Fos in the rat hippocampus and
      frontal cortex. MK-801 induced c-Fos in these brain regions in a nonlinear dose
      response relationship. Maximum effect was achieved with 1-2 mg/kg of MK-801. The
      level of c-Fos paralleled animal hyperkinetic behavior, suggesting the role of c
      Fos in the induced psychotomimetic behaviors. Pretreatment with MK-801 dose
      dependently attenuated both the seizures and c-Fos expression by ECS. However, at
      an MK-801 pretreatment dose of 8 mg/kg, which completely blocked ECS-induced
      seizure, the induction of c-Fos was not completely blocked, suggesting non-NMDA
      mediated pathways of the induction of c-Fos by ECS.

PMID- 11999903
TI  - Distribution of parkin in the adult rat brain.
AB  - A mutation in the parkin gene has been identified as the cause for an autosomal
      recessively inherited form of Parkinson's disease (PD). The authors have recently
      isolated the mRNA coding for the rat homolog of parkin and showed its widespread
      expression in the central nervous system (CNS) by in situ hybridization. In the
      present study, we investigated the distribution of parkin in the rat CNS with a
      polyclonal antibody that reacts with a approximately 52-kDa protein, mainly
      localized in the cytoplasm and corresponding to the predicted molecular mass of
      parkin. Immunohistochemistry on adult rat brain sections showed a widespread
      distribution of parkin. This included labeling of cell bodies, nuclei as well as
      processes in the hippocampus, cerebral cortex, cerebellum, and several nuclei in
      the brainstem. The regional expression of parkin-immunoreactivity (IR) correlated
      well with the parkin-mRNA levels assessed by real-time quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). This study provides the
      detailed analysis of the regional and cellular distribution of parkin in the rat
      brain and may be useful in elucidating its pathophysiological role.

PMID- 11999904
TI  - Prevalence of smoking in psychiatric patients.
AB  - Compelling evidence that tobacco-smoking is a form of drug addiction exists. The
      aim of this study is to determine the following: (1) prevalence of tobacco
      smoking and of nicotine dependence in French psychiatric patients; (2) rates and
      patterns of tobacco smoking and of nicotine dependence according to diagnosis;
      (3) relationship between current smoking status and antipsychotic medications;
      and (4) relationship between cigarette smoking and neurological side effects
      induced by neuroleptics. A population of 711 psychiatric in- and outpatients was
      assessed using: (1) a detailed smoking self-questionnaire for smoking history and
      nicotine dependence; and (2) a questionnaire for staff covering treatments and
      DSMIII-R diagnoses. Data were analyzed using chi2 analysis of variance (ANOVA)
      tests (one factor) for quantitative comparisons between groups of patients, and
      analysis of covariance (ANCOVA) test with age covariate was performed for age
      dependent variables. Prevalence of smoking in the population of psychiatric
      patients was significantly higher than in the French general population.
      Diagnoses among current smokers were mainly substance-related disorder and
      schizophrenia. The authors established correlations between prevalence of smoking
      and age, sex, marital and socioeconomic status, alcohol use, coffee consumption
      and other psychoactive substance use or abuse. The authors did not find
      relationship between smoking prevalence and institutionalization. Neuroleptic
      neurological side effects were significantly fewer among smokers compared to
      nonsmokers. However, the rate of smokers was significantly higher in psychiatric
      patients receiving neuroleptic drugs. Nicotine abuse in psychiatric patients, and
      especially in schizophrenic patients, could support the hypothesis that smoking
      is consistent with self-medication.

PMID- 11999905
TI  - Can valerian improve the sleep of insomniacs after benzodiazepine withdrawal?
AB  - PURPOSE: The authors studied the sleep of patients with insomnia who complained
      of poor sleep despite chronic use of benzodiazepines (BZDs). The sample consisted
      of 19 patients (mean age 43.3+/-10.6 years) with primary insomnia (DSM-IV), who
      had taken BZDs nightly, for 7.1+/-5.4 years. The control group was composed of 18
      healthy individuals (mean age 37+/-8 years). Sleep electroencephalogram (EEG) of
      the patients was analyzed with period amplitude analysis (PAA) and associated
      algorithms, during chronic BZD use (Night 1), and after 15 days of a valerian
      placebo trial (initiated after washout of BZD, Night 2). Sleep of control
      subjects was monitored in parallel. RESULTS: Valerian subjects reported
      significantly better subjective sleep quality than placebo ones, after BZD
      withdrawal, despite the presence of a few side effects. However, some of the
      differences found in sleep structure between Night 1 and Night 2 in both the
      valerian and placebo groups may be due to the sleep recovery process after BZD
      washout. Example of this are: the decrease in Sleep Stage 2 and in sigma count;
      the increase in slow-wave sleep (SWS), and delta count, which were found to be
      altered by BZD ingestion. There was a significant decrease in wake time after
      sleep onset (WASO) in valerian subjects when compared to placebo subjects;
      results were similar to normal controls. Nonetheless, valerian-treated patients
      also presented longer sleep latency and increased alpha count in SWS than control
      subjects. CONCLUSIONS: The decrease in WASO associated with the mild anxiolytic
      effect of valerian appeared to be the major contributor to subjective sleep
      quality improvement found after 2-week of treatment in insomniacs who had
      withdrawn from BDZs. Despite subjective improvement, sleep data showed that
      valerian did not produce faster sleep onset; the increase in alpha count compared
      with normal controls may point to residual hyperarousabilty, which is known to
      play a role in insomnia. Nonetheless, we lack data on the extent to which a
      sedative drug can improve alpha sleep EEG. Thus, the authors suggest that
      valerian had a positive effect on withdrawal from BDZ use.

PMID- 11999906
TI  - The use of drug monotherapy in psychiatric inpatient treatment.
AB  - OBJECTIVE: Monotherapy has always been the goal in psychiatric drug treatment,
      but it does not seem to be very common in everyday practice. METHOD: The
      available literature on the frequency of monotherapy or polytherapy with
      psychotropic agents in psychiatric inpatient treatment is reviewed. FINDINGS:
      Taken all together (28 studies on 42 treatment facilities), the mean number of
      psychotropics prescribed was 2.47, the rate of monotherapy was 36.2% and 37.9% of
      inpatients received > or = 3 different drugs. Comparing the last three decades, a
      significant decline of the rate of monotherapy was found, topping at 47.8% in the
      70s and falling to 19.6% in the 90s. The mean number of psychotropic drugs
      prescribed rose from 2.2 to 2.9 and the number of patients receiving > or = 3
      psychotropics rose from 27.5 to 49.7%. CONCLUSION: Though it is still mandatory
      to avoid unsound polypharmacy, we must assume that the occasions for polypharmacy
      are increasing. New psychotropic drugs, increasing comorbidity and augmentation
      strategies may be incentives for polydrug use. Since in most countries the number
      of psychiatric beds declines, inpatient treatment has to deal with the most
      severe, often treatment-resistant patients requiring special therapies.

PMID- 11999907
TI  - Receptor profile of P88-8991 and P95-12113, metabolites of the novel
      antipsychotic iloperidone.
AB  - Iloperidone is a novel atypical antipsychotic compound currently under clinical
      development for the treatment of psychotic disorders. In radioligand binding
      studies, iloperidone binds with high affinity to serotonin (5-HT) 5-HT2A and
      noradrenaline alpha1 and alpha2C receptors [Neuropsychopharmacology (2001) 25,
      904-914]. The human metabolism of iloperidone generates two major metabolites,
      P88-8991 and P95-12113. The aim of this study was to compare the receptor
      affinity profile of P88-8991 and P95-12113 with that of the parent compound. The
      receptor affinity profile of P88-8991 is comparable to that of iloperidone. This
      metabolite binds to the following monoamine receptors (pKi values in nM):
      serotonin 5-HT2A receptors (9.56), adrenergic alpha1 (8.08) and alpha2C (7.79)
      receptors, and D2A receptors (7.80). Lower affinity is seen for other dopamine,
      serotonin, alpha2-adrenergic and histamine H1 receptors. In contrast, P95-12113
      shows affinity for 5-HT2A receptors (pKi 8.15; which is 60-fold lower than that
      of iloperidone), adrenergic alpha1 (7.67), alpha2C (7.32) and alpha2B (7.08)
      receptors. Given this affinity profile, and the observation that P95-12113 does
      not readily cross the blood-brain barrier, it is unlikely that this metabolite
      contributes to the therapeutic effect of iloperidone in patients with
      schizophrenia. However, the comparable receptor binding profile of P88-8991
      indicates that it is likely to contribute to the clinical profile of iloperidone.

PMID- 11999908
TI  - Effects of short- and long-term lithium treatment on kidney functioning in
      patients with bipolar mood disorder.
AB  - Lithium (Li) carbonate has been reported to be able to cause some reversible
      functional changes in the kidney. In this study, the authors aimed to investigate
      whether the duration of Li treatment is the primary determinant of the changes in
      renal functioning due to the Li treatment. For this purpose, 10 Li-naive (mean
      age+/-S.D.: 34.50+/-4.85), 10 short-term (mean age+/-S.D.: 31.77+/-7.61) and 10
      long-term (mean age+/-S.D.: 36.60+/-10.15) Li-treated bipolar patients were
      included in the study. Serum blood urea nitrogen (BUN) and creatinine, urine
      creatinine levels, creatinine clearance, urine osmolality before and after 8-h
      water deprivation and urine osmolality after desmopressin injection were measured
      in all patients. Serum BUN and creatinine levels were within the normal limits
      and not statistically different among the groups. Creatinine clearance of the
      long-term Li-treated group was significantly lower than both that of the Li-naive
      group and that of the short-term Li-treated group. After 8-h water deprivation
      and also after desmopressin injection, no difference was found among the groups
      in terms of urine osmolality. However, when each patient was evaluated
      individually in terms of their renal concentrating ability, partial nephrogenic
      diabetes insipidus was diagnosed in four patients on long-term and in two
      patients on short-term Li treatment. To our surprise, hypothalamic diabetes
      insipidus was also diagnosed in other two patients on long-term Li treatment.
      These results demonstrate that long-term Li treatment may cause impairment in
      renal concentrating ability, some of which may originate from the effects of Li
      on vasopressin on hypothalamic level, and a decrease in glomerular filtration
      rate (GFR). In the light of these data, we can conclude that long-term
      administration of Li may be a risk factor for Li-induced renal impairment, which
      is a progressive effect in nature.

PMID- 11999909
TI  - Effects of NG-nitro-L-arginine methyl ester, 7-nitro indazole, and agmatine on
      pentylenetetrazol-induced discriminative stimulus in Long-Evans rats.
AB  - This study was undertaken to determine any role that nitric oxide (NO) may play
      in the discriminative stimuli produced by pentylenetetrazol (PTZ). The PTZ
      induced discriminative stimulus is pharmacologically similar to anxiety in humans
      and is used in a behavioral assay of anxiety (the PTZ model of anxiety). In the
      present study, effects of L-N(G)-nitro arginine methyl ester (L-NAME), 7
      nitroindazole (7-NI) and agmatine, NO synthase (NOS) inhibitors, on PTZ-induced
      discriminative stimulus were investigated in male Long-Evans rats (330-350 g).
      Rats were trained to discriminate PTZ (16 mg/kg) from saline using a two-lever,
      food-reinforced choice procedure (FR 10). The rats that met the training criteria
      were injected with L-NAME (15, 30, and 60 mg/kg), 7-NI (15 and 30 mg/kg),
      agmatine (20, 40, and 60 mg/kg), and saline or vehicle intraperitoneally before
      each test. They were tested for the PTZ-discrimination to determine if the NOS
      inhibitors produce discriminative stimulus similar to PTZ or if they block PTZ
      induced discrimination. Treatment with the NOS inhibitory drugs neither
      substituted for PTZ nor altered the PTZ lever selection in any other way. These
      findings suggest that PTZ-induced discriminative stimulus may not be related to
      NO-mediated central mechanisms.

PMID- 11999910
TI  - Comparison of prolactin concentrations between haloperidol and bromperidol
      treatments in schizophrenic patients.
AB  - The antipsychotic drug, bromperidol, is a close structural analogue of
      haloperidol. These two drugs also have similarities in metabolic pathways and
      pharmacological properties. In the present study, the prolactin concentrations in
      plasma during bromperidol versus haloperidol treatments were compared in the same
      individuals. The subjects were 22 schizophrenic inpatients, who first received
      bromperidol 12 mg/day for at least 2 weeks followed by haloperidol 12 mg/day. The
      prolactin concentration in plasma during bromperidol treatment (median and range;
      24 and 7-93 ng/ml, respectively) was significantly (P< .01) lower than during
      haloperidol treatment (32 and 8-102 ng/ml), although the difference was small.
      The mean (+/- S.D.) plasma concentration of bromperidol was significantly lower
      than that of haloperidol (20.8+/-8.0 vs. 28.0+/-13.1 nmol/l, P<.05). Prolactin
      concentrations during both treatment phases correlated well in individuals
      (r's=.813, P<.001), while no correlation was observed between plasma
      concentrations of haloperidol and bromperidol (r=.053, ns). These findings
      suggest that slightly higher prolactin concentration does not necessarily lead to
      increased risk of hyperprolactinemia during bromperidol treatment compared with
      haloperidol treatment. In addition, it is suggested that both drugs show similar
      pharmacodynamic response despite the difference in pharmacokinetics in the same
      individuals.

PMID- 11999911
TI  - Different neuroendocrine profiles of remitted and nonremitted schizophrenic
      patients.
AB  - BACKGROUND: Thyrotropin-releasing hormone (TRH) test and Dexamethasone
      Suppression Test (DST) are two neuroendocrine tests that have been extensively
      used in an attempt to predict treatment response and outcome in schizophrenia.
      The objectives of this study were to investigate (1) the relationship between TRH
      test and DST and various psychiatric symptoms and (2) the potential value of
      these tests in prediction of short-term outcome in schizophrenic patients.
      METHODS: TRH test and DST were administered to 58 patients with schizophrenia.
      All patients were evaluated with a battery of rating scales before neuroendocrine
      test procedures and at regular intervals for 1 year. Patients were divided into
      two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28).
      Baseline results of these two groups were compared with each other and 30 healthy
      controls. RESULTS: Basal levels of total T3 (T3T) and free T3 (T3F) were higher
      in RP group than controls. Basal prolactin (PRL) level was higher in RP group,
      but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid
      stimulating hormone (TSH) levels of NRP were significantly higher than those of
      RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP
      and control group. Blunted TSH response rate in RP group was higher significantly
      compared to other two groups. CONCLUSIONS: The data implicate that higher basal
      TSH and GH levels may be associated with a poorer treatment response, whereas
      higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression
      on the DST may indicate a better response in schizophrenics.

PMID- 11999912
TI  - Venlafaxine versus stimulant therapy in patients with dual diagnosis ADD and
      depression.
AB  - BACKGROUND: Adult attention-deficit disorder (ADD) may either present as chronic
      depression or be comorbid with major depressive disorder (MDD). The present study
      examined treatment outcome with antidepressants and/or stimulants in adults with
      ADD who initially presented with a diagnosis of MDD. METHOD: Seventeen patients
      with comorbid MDD and ADD were identified: 65% had a history of hyperactivity in
      childhood, and 41% had a history of treatment nonresponse to two or more
      antidepressants. Retrospective analysis was performed with patients who received
      one of three treatments: (i) venlafaxine, bupropion, or tricyclic antidepressant
      (TCA) monotherapy; (ii) stimulant monotherapy; or (iii) stimulant plus
      antidepressant therapy. Outcome was based upon change in both MDD and ADD
      symptoms. RESULTS: Venlafaxine-treated patients (80%) versus patients taking
      stimulant therapy alone (33%) had at least a moderate reduction in both MDD and
      ADD symptoms (chi2=2.40, Fisher exact P=.13). Similarly, 88% of patients on
      stimulants plus antidepressant therapy also showed a reduction in both MDD and
      ADD symptoms (versus stimulant monotherapy) (chi2 = 7.22, Fisher exact P=.018).
      There was no difference in response rates between venlafaxine monotherapy and
      combination stimulant plus antidepressant therapy (chi2=0.13, Fisher exact p=ns).
      CONCLUSION: Although preliminary in nature, these data suggest that venlafaxine
      monotherapy may have similar efficacy to a treatment with a combination of
      stimulant plus antidepressant therapy, and superior to stimulant therapy alone,
      in patients with comorbid MDD and ADD. Controlled, prospective trials with larger
      patient samples will be needed to confirm these preliminary observations.

PMID- 11999913
TI  - A randomized trial of a specific adherence enhancement program in sertraline
      treated adults with major depressive disorder in a primary care setting.
AB  - Adherence to drug therapy is a limitation in treatment success for major
      depressive disorder (MDD). The influence of RHYTHMS, an information and ongoing
      interactive program designed by Pfizer Pharmaceuticals, to address patient
      adherence to sertraline therapy was evaluated in a primary care setting using a
      randomized, double-blind, parallel group controlled trial over 29 weeks.
      Remission was the primary outcome evaluated. At study completion, no
      statistically significance between group differences was noted for remission
      rates, treatment adherence or mean Hamilton Depression Rating Scale (HDRS) score.
      However, the RHYTHMS group reported significantly greater satisfaction with
      knowledge received about depression and its treatment and demonstrated
      significantly greater satisfaction with treatment received. We conclude that the
      application of RHYTHMS in a primary care setting has a substantial role in
      improving satisfaction with sertraline treatment by patients with MDD.

PMID- 11999914
TI  - Clinical outcome and tolerability of sertraline in major depression: a study with
      plasma levels.
AB  - Sertraline (SRT) has been shown to be an effective antidepressant in extensive
      clinical trial programs but data on plasma concentrations regarding clinical
      outcome and tolerability are lacking. Twenty-one out-patients of both sexes, with
      mean age of 50.23 years (S.D. = 17.37), affected by major depressive disorder,
      recurrent (Diagnostic and Statistical Manual of Mental Disorder--IV, DSM-IV),
      were treated with 25-150 mg of SRT once a day (mean=66.26 mg, S.D.=30.50) for 30
      days. Clinical evaluation was assessed at baseline (T0), after 15 days (T15), and
      then after 30 days (T30). Plasma samples for SRT level determination were
      collected at T30. Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale
      for Depression (HRS-D), and Hamilton Rating Scale for Anxiety (HRS-A) showed a
      significant improvement during the study (P<.01 vs. T0). The most commonly
      reported side effects were nausea (19%), cephalalgia (9.5%), dry mouth (9.5%),
      decreased libido (9.5%), tremor (4.7%), and tachycardia (4.7%). SRT plasma levels
      ranged from 2.82 to 112.20 ng/ml (mean=40.42 ng/ml, S.D.=26.93). No correlation
      between SRT plasma levels and clinical improvement or side effects were observed.
      Drug plasma level determination does not seem be strictly necessary from a
      clinical point of view but further research seems advisable in patients at risk
      like elderly and during long-term studies.

PMID- 11999915
TI  - Agranulocytosis during clozapine therapy.
AB  - Granulocytopenia and agranulocytosis are considered among the most dangerous
      adverse effects of clozapine. During the last 15-year period, this atypical
      antipsychotic agent has been administered to 750 patients managed at the
      Emergency Psychiatry Services and Clinical Pharmacology Unit of the National
      Institute of Psychiatry and Neurology (NIPandN; Budapest, Hungary).
      Granulocytopenia was ascertained in seven, whereas agranulocytosis was diagnosed
      in two patients of this population. The latter two comprised a 42-year-old female
      with schizoaffective psychosis and a 35-year-old male with paranoid
      schizophrenia. The female patient received clozapine in a daily dose of 400 mg,
      which induced agranulocytosis after 2 months. The male patient was treated with
      225-mg/day clozapine and the time to the diagnosis of agranulocytosis was 6
      weeks. These adverse reactions were recognized early and the appropriate
      treatment of agranulocytosis resulted in complete recovery in both cases.

PMID- 11999916
TI  - Treatment of comorbid opiate addiction and attention-deficit hyperactivity
      disorder (residual type) with moclobemide: a case report.
AB  - Moclobemide is a specific and reversible monoamine oxidase-A (MAO-A) inhibitor.
      Studies show that it is an effective and well-tolerated treatment for attention
      deficit hyperactivity disorder (ADHD). A number of reports suggest that ADHD may
      have a causal influence on the development of substance use disorders. The
      authors describe the use of moclobemide in a 27-year-old patient with comorbid
      opiate addiction and ADHD (residual type). The positive clinical response shown
      suggests that moclobemide may have a particular interest in the treatment of drug
      dependent patients with current ADHD.

PMID- 11999917
TI  - The brain decade in debate: V-Neurobiology of depression.

PMID- 11999918
TI  - Why Susie sells seashells by the seashore: implicit egotism and major life
      decisions.
AB  - Because most people possess positive associations about themselves, most people
      prefer things that are connected to the self (e.g., the letters in one's name).
      The authors refer to such preferences as implicit egotism. Ten studies assessed
      the role of implicit egotism in 2 major life decisions: where people choose to
      live and what people choose to do for a living. Studies 1-5 showed that people
      are disproportionately likely to live in places whose names resemble their own
      first or last names (e.g., people named Louis are disproportionately likely to
      live in St. Louis). Study 6 extended this finding to birthday number preferences.
      People were disproportionately likely to live in cities whose names began with
      their birthday numbers (e.g., Two Harbors, MN). Studies 7-10 suggested that
      people disproportionately choose careers whose labels resemble their names (e.g.,
      people named Dennis or Denise are overrepresented among dentists). Implicit
      egotism appears to influence major life decisions. This idea stands in sharp
      contrast to many models of rational choice and attests to the importance of
      understanding implicit beliefs.

PMID- 11999919
TI  - Racism, ideology, and affirmative action revisited: the antecedents and
      consequences of "principled objections" to affirmative action.
AB  - In 2 studies, the antecedents and consequences of "principled objections" to
      affirmative action (specific, "race-neutral" reasons for opposing the policy)
      among Whites were examined. In Study 1. data from a probability sample of Los
      Angeles adults indicated the following: (a) that principled-objection endorsement
      was driven not merely by race-neutral values but also by dominance-related
      concerns like racism; (b) that principled objections mediated the effects of
      group dominance; and (c) that education strengthened-rather than attenuated-the
      relationship between dominance-related concerns and principled objections.
      whereas it left the relationship between race-neutral values and the latter
      essentially unchanged. In Study 2, the education findings were conceptually
      replicated in a panel study of undergraduates: The completion of additional years
      of college boosted the correlation between racism and principled objections,
      whereas it had no effect on the predictive power of conservatism. These results
      provide support for a general group-dominance approach, which suggests that
      factors like racism continue to shape White opposition to race-targeted policies.

PMID- 11999920
TI  - Decisions and revisions: the affective forecasting of changeable outcomes.
AB  - People prefer to make changeable decisions rather than unchangeable decisions
      because they do not realize that they may be more satisfied with the latter.
      Photography students believed that having the opportunity to change their minds
      about which prints to keep would not influence their liking of the prints.
      However, those who had the opportunity to change their minds liked their prints
      less than those who did not (Study 1). Although the opportunity to change their
      minds impaired the postdecisional processes that normally promote satisfaction
      (Study 2a), most participants wanted to have that opportunity (Study 2b). The
      results demonstrate that errors in affective forecasting can lead people to
      behave in ways that do not optimize their happiness and well-being.

PMID- 11999921
TI  - Self-serving interpretations of flattery: why ingratiation works.
AB  - Persons who are flattered are more likely to assign credibility to and like the
      flatterer than observers, presumably because they are motivated by vanity. In
      existing studies, however, the difference between targets and observers has been
      confounded with other variables. The present experiments demonstrate that the
      target-observer difference in judgments of an ingratiator is not affected by
      these confounding variables, such as cognitive resources, the motive to like
      one's interaction partner, or to form an accurate impression, or mood. Results
      further suggest that, whereas cognitive responses to ingratiation are different
      among participants with high versus low self-esteem, affective responses and
      judgments of the ingratiator are not qualified by any personality variables.

PMID- 11999922
TI  - The anxiety-buffering function of close relationships: evidence that relationship
      commitment acts as a terror management mechanism.
AB  - Three studies examined the terror management function of romantic commitment. In
      Study 1 (N = 94), making mortality salient led to higher reports of romantic
      commitment on the Dimensions of Commitment Inventory (J. M. Adams & W. H. Jones,
      1997) than control conditions. In Study 2 (N = 60), the contextual salience of
      thoughts about romantic commitment reduced the effects of mortality salience on
      judgments of social transgressions. In Study 3 (N = 100), the induction of
      thoughts about problems in romantic relationships led to higher accessibility of
      death-related thoughts than did the induction of thoughts about either academic
      problems or a neutral theme. The findings expand terror management theory,
      emphasizing the anxiety-buffering function of close relationships.

PMID- 11999923
TI  - Motivated self-stereotyping: heightened assimilation and differentiation needs
      result in increased levels of positive and negative self-stereotyping.
AB  - This research was conducted to explore the impact of assimilation and
      differentiation needs on content-specific self-stereotyping. According to optimal
      distinctiveness theory (M. B. Brewer, 1991), social identities serve the function
      of satisfying individuals' need for assimilation (in-group inclusion) and their
      need for differentiation (distinctiveness from others). It was proposed that one
      of the ways optimal social identities are maintained is through self
      stereotyping. In 3 studies, the needs for assimilation and differentiation were
      experimentally manipulated, and support was found for increased self-stereotyping
      in response to heightened need arousal across both self-report and behavioral
      measures and across different social groups. Results also demonstrated that only
      those participants who were highly identified with their in-group were willing to
      engage in negative self-stereotyping.

PMID- 11999924
TI  - Kindred spirits? The benefits of egocentrism in close relationships.
AB  - The authors argue that people are happiest in their relationships when they
      believe they have found a kindred spirit, someone who understands them and shares
      their experiences. As reality may not always be that accommodating, however,
      intimates may find this sense of confidence by egocentrically assuming that their
      partners are mirrors of themselves. Both members of dating and married couples
      completed measures of satisfaction and felt understanding. They also described
      their own and their partners' traits, values, and day-to-day feelings. The
      results revealed that people in satisfying and stable relationships assimilated
      their partners to themselves, perceiving similarities that were not evident in
      reality. Such egocentrism predicted greater feelings of being understood, and
      feeling understood mediated the link between egocentrism and satisfaction in
      marriage.

PMID- 11999925
TI  - Culture, personality, and subjective well-being: integrating process models of
      life satisfaction.
AB  - The authors examined the interplay of personality and cultural factors in the
      prediction of the affective (hedonic balance) and the cognitive (life
      satisfaction) components of subjective well-being (SWB). They predicted that the
      influence of personality on life satisfaction is mediated by hedonic balance and
      that the relation between hedonic balance and life satisfaction is moderated by
      culture. As a consequence, they predicted that the influence of personality on
      life satisfaction is also moderated by culture. Participants from 2
      individualistic cultures (United States, Germany) and 3 collectivistic cultures
      (Japan, Mexico, Ghana) completed measures of Extraversion, Neuroticism, hedonic
      balance, and life satisfaction. As predicted, Extraversion and Neuroticism
      influenced hedonic balance to the same degree in all cultures, and hedonic
      balance was a stronger predictor of life satisfaction in individualistic than in
      collectivistic cultures. The influence of Extraversion and Neuroticism on life
      satisfaction was largely mediated by hedonic balance. The results suggest that
      the influence of personality on the emotional component of SWB is pancultural,
      whereas the influence of personality on the cognitive component of SWB is
      moderated by culture.

PMID- 11999926
TI  - Extending the search for folk personality constructs: the dimensionality of the
      personality-relevant proverb domain.
AB  - College students (95 men and 264 women) rated how well 211 familiar proverbs
      described their behavior and beliefs. A factor analysis of these data yielded 7
      major dimensions; many of the factors were similar to recognized lexical
      personality factors. Big Five Conscientiousness and Neuroticism were each
      strongly associated with a single proverb dimension (interpreted as Restraint and
      Enjoys Life, respectively). Big Five Agreeableness, Extraversion, and
      Intellect/Imagination were all associated with several proverb dimensions.
      Agreeableness was most strongly associated with proverb dimensions representing
      Machiavellian behavior and strong Group Ties, and both Extraversion and Intellect
      showed particularly notable associations with an Achievement Striving dimension.
      The 2 remaining proverb dimensions, which represented a belief that Life is Fair
      and an attitude of Cynicism, could not be accounted for by the Big Five.

PMID- 11999927
TI  - Proneness to hypomania/mania symptoms or depression symptoms and asymmetrical
      frontal cortical responses to an anger-evoking event.
AB  - The behavioral approach system (BAS) reflects the propensity to respond to
      signals of reward, including stimuli associated with safety and goal-oriented
      attack (e.g., anger). Hypomania/mania has been posited to involve increased BAS
      activity. In contrast, depression has been posited to involve decreased BAS
      activity. Building on past research, which suggests that increased left frontal
      cortical activity is a neurophysiological index of BAS activity, the present
      research tested the hypotheses that proneness toward hypomania/mania symptoms
      would be related to increased relative left frontal activity and that proneness
      toward depression symptoms would be related to decreased relative left frontal
      activity in response to an anger-evoking event. Results from 67 individuals who
      had completed a measure of proneness toward these affective symptoms and were
      exposed to an anger-evoking event supported the hypotheses.

PMID- 11999928
TI  - Does resting electroencephalograph asymmetry reflect a trait? an application of
      latent state-trait theory.
AB  - Recent research on brain asymmetry and emotion treated measures of resting
      electroencephalograph (EEG) asymmetry as genuine trait variables, but
      inconsistency in reported findings and modest retest correlations of baseline
      asymmetry are not consistent with this practice. The present study examined the
      alternative hypothesis that resting EEG asymmetry represents a superimposition of
      a traitlike activation asymmetry with substantial state-dependent fluctuations.
      Resting EEG was collected from 59 participants on 4 occasions of measurement, and
      data were analyzed in terms of latent state-trait theory. For most scalp regions,
      about 60% of the variance of the asymmetry measure was due to individual
      differences on a temporally stable latent trait, and 40% of the variance was due
      to occasion-specific fluctuations, but measurement errors were negligible.
      Further analyses indicated that these fluctuations might be efficiently reduced
      by aggregation across several occasions.

PMID- 11999929
TI  - Life-management strategies of selection, optimization, and compensation:
      measurement by self-report and construct validity.
AB  - The authors examined the usefulness of a self-report measure for elective
      selection, loss-based selection. optimization, and compensation (SOC) as
      strategies of life management. The expected 4-factor solution was obtained in 2
      independent samples (N = 218, 14-87 years; N = 181, 18-89 years) exhibiting high
      retest stability across 4 weeks (r(tt) = .74-82). As expected, middle-aged adults
      showed higher endorsement of SOC than younger and older adults. Moreover, SOC
      showed meaningful convergent and divergent associations to other psychological
      constructs (e.g., thinking styles, NEO) and evinced positive correlations with
      measures of well-being which were maintained after other personality and
      motivational constructs were controlled for. Initial evidence on behavioral
      associations involving SOC obtained in other studies is summarized.

PMID- 11999930
TI  - Stimulation seeking and intelligence: a prospective longitudinal study.
AB  - The prediction that high stimulation seeking 3-year-olds would have higher IQs by
      11 years old was tested in 1,795 children on whom behavioral measures of
      stimulation seeking were taken at 3 years, together with cognitive ability at 11
      years. High 3-year-old stimulation seekers scored 12 points higher on total IQ at
      age 11 compared with low stimulation seekers and also had superior scholastic and
      reading ability. Results replicated across independent samples and were found for
      all gender and ethnic groups. Effect sizes for the relationship between age 3
      stimulation seeking and age 11 IQ ranged from 0.52 to 0.87. Findings appear to be
      the first to show a prospective link between stimulation seeking and
      intelligence. It is hypothesized that young stimulation seekers create for
      themselves an enriched environment that stimulates cognitive development.

PMID- 11999931
TI  - Victim and offender accounts of interpersonal conflict: autobiographical
      narratives of forgiveness and unforgiveness.
AB  - Participants wrote 2 narratives that described an incident in which they angered
      or hurt someone (offender) or in which someone angered or hurt them (victim) and
      the offense was forgiven or not forgiven. Victims portrayed the offense as
      continuing (open), and offenders portrayed the offense as over (closed).
      Forgiveness narratives portrayed offenses as closed and with positive outcomes;
      however, for some victims, forgiveness coincided with continued anger, suggesting
      incomplete forgiveness. Dispositional empathy was associated with more benign
      interpretations of offenses, and situational empathy (e.g., for the offender) was
      associated with victims' forgiveness. In contrast, offenders' empathy for victims
      was associated with less self-forgiveness. Thus, both victim or offender role and
      forgiveness must be considered to understand narratives of interpersonal
      offenses.

PMID- 11999932
TI  - A longitudinal study of condylar growth and mandibular rotation in untreated
      subjects with class II malocclusion.
AB  - Condylar growth intensity, mandibular growth rotation, and the association
      between growth intensity and rotation were evaluated in 32 untreated subjects
      with Class II malocclusions. Condylar growth was measured on serial lateral head
      films annually from ages 8 to 13. The analysis showed that the growth intensity
      of the condyles varied only slightly between girls and boys, with boys growing
      more. Fluctuations in growth intensity were observed in all subjects from year to
      year. None of the individuals maintained a consistent growth velocity over two or
      more consecutive years. The average condylar growth intensity was two to three mm
      per year throughout the period from age 8 1/2 to 12 1/2 for both sexes, with boys
      growing slightly faster than girls at some ages. The greatest growth velocity
      observed was eight mm in one year, which was seen in one boy. Three girls had as
      much as six mm of condylar growth in one year. Average mandibular rotation was 
      0.8 (+/- 0.5 SD) per year in boys and -0.6 degrees (+/- 0.6 SD) in girls, with
      great individual variation for both sexes. Ninety percent of the subjects showed
      some degree of anterior or forward rotation; only one subject demonstrated
      posterior rotation and three demonstrated almost no rotation. No clear
      relationship was found between amount of condylar growth and mandibular rotation.
      This study shows that condylar growth intensity varies considerably between
      subjects and from year to year in each subject, and suggests that clinicians need
      to be conservative when estimating treatment length for a patient with a Class II
      malocclusion.

PMID- 11999933
TI  - Relationship between congenitally missing lower third molars and late formation
      of tooth germs.
AB  - In this investigation, we used longitudinal panoramic radiographs from 96
      subjects (47 boys, 49 girls) who did not have any congenital disease. The
      subjects were selected based on their age at the initial radiograph and the
      number and frequency of radiographs. Lower left premolars and second molars were
      used as parameters to identify factors that influence the age of formation of the
      third molar. We classified teeth into eight formation stages according to the
      method of Demirjian. The age at the beginning of formation of the lower third
      molar was determined with a regression equation of longitudinal data. The highest
      correlation existed between the age at the beginning of formation of the third
      molar and the formation stage of the second molar. We conclude that late
      formation of tooth germs is one of the factors that leads to the congenital
      absence of lower third molars. Furthermore, we assume that when the tooth germ of
      the lower third molar has not appeared at stage 7 of formation of the second
      molar, the probability of the third molar being missing is 100%.

PMID- 11999934
TI  - Does the timing and method of rapid maxillary expansion have an effect on the
      changes in nasal dimensions?
AB  - The aim of this study was to assess the effects of rapid maxillary expansion
      (RME) and surgical assisted rapid maxillary expansion (SARME) on nasopharyngeal
      area. The study group consisted of 30 subjects in the permanent dentition who had
      both maxillary constriction and a posterior cross-bite. The patients were divided
      into two groups, RME and SARME. The subjects in the RME group consisted of 15
      patients (eight girls, seven boys) whose average age was 12.1 +/- 1.1 years. The
      SARME group also consisted of 15 patients (eight boys, seven girls) whose mean
      age was 18.4 +/- 1.4 years. An acrylic bonded RME appliance was used in both
      groups. Surgery was performed using lateral cortical osteotomies in the SARME
      group. The nasopharyngeal and respiratory area was determined using a digital
      planimeter on lateral cephalometric radiographs taken before and after RME. Nasal
      cavity width was evaluated on postero-anterior radiographs. Nasal dimension was
      measured using planimeter measurements of the respiratory and nasopharyngeal
      areas before and after treatment. The data obtained were analyzed using SPSS.
      Comparisons within the groups were carried out with paired t-tests and
      comparisons between the groups were with a Student's t-test. In both groups, the
      respiratory area and the ratio of the respiratory area to nasopharyngeal (RA/NA)
      area increased following RME. There were no statistically significant differences
      between the groups. Nasal cavity width and maxillary width also increased, but
      the difference between the groups was not significant. Following RME, various
      differences in both the maxilla and surrounding bones occurred and nasal width
      increased with a decrease in nasal airway resistance. At the end of treatment
      there were increases in the width of the nasal floor near the midpalatal suture
      and nasal cavity. As the maxillary structures separated, the outer walls of the
      nasal cavity moved laterally resulting in an increase in internasal volume. Nasal
      resistance decreased and respiratory area increased in patients treated with RME.

PMID- 11999935
TI  - Relationship between cephalometric characteristics and obstructive sites in
      obstructive sleep apnea syndrome.
AB  - Patients with obstructive sleep apnea syndrome (OSAS) have characteristic
      dentofacial features, but the sites of obstruction differ greatly. The purpose of
      this study was to investigate the dentofacial characteristics of patients with
      OSAS with respect to the obstructive sites. The subjects consisted of 30 Japanese
      men with OSAS divided into 3 groups of 10 patients each. One group had
      obstruction at the retropalatal and retroglossal region (Rp + Rg group), a second
      group had obstruction at the retropalatal region (Rp group), and a third group
      had obstruction due to tonsillar hypertrophy (tonsillar hypertrophy group). To
      identify the Rp + Rg and Rp groups, dynamic magnetic resonance imaging (MRI) was
      used. To identify the tonsillar hypertrophy group, Mackenzie's classification,
      axial MRI, and the weight of the tonsils were used. A control group was composed
      of 10 Japanese men showing no symptoms suggestive of OSAS. Lateral cephalometric
      radiographs were obtained for all of the subjects, and analysis of variance was
      performed for the 46 cephalometric parameters. Among the many dentofacial
      characteristics of OSAS patients, the tendencies for retrognathia, micrognathia,
      and skeletal Class II were strongest in the Rp + Rg group and somewhat strong in
      the Rp group. The presence of a long soft palate was dominant in the Rp group,
      whereas the tendency for a long face was dominant in the tonsillar hypertrophy
      group. All of the groups shared the characteristic of having an inferior position
      of the hyoid bone. Based on the results of the current study, we conclude that
      many features of OSAS are specifically related to each obstructive type of OSAS.

PMID- 11999936
TI  - Powered vs manual tooth brushing in fixed appliance patients: a short term
      randomized clinical trial.
AB  - Sixty-three orthodontic patients wearing upper and lower fixed appliances were
      randomly assigned to use either a powered toothbrush fitted with a modified
      orthodontic brush head (Braun Oral-B Plaque Remover 3D) or a manual toothbrush
      (Reach Compact Medium). A trained hygienist instructed each patient on the proper
      use of the allocated brush. Measurements of plaque and gingival health were made
      at baseline, at four weeks, and at eight weeks. Data for each group were analyzed
      using paired t-tests. Patients using the powered toothbrush showed a significant
      reduction in percentage interdental bleeding scores from baseline to four weeks (
      12.7, P = .003) and this was still apparent at eight weeks (-8.6, P = .028),
      although there were no statistically significant changes in either plaque or
      gingivitis scores for this group. Those patients using a manual toothbrush showed
      a significant reduction in mean plaque score from baseline (four weeks = -0.18, P
      = < .001; eight weeks = -0.12, P = .016), but gingivitis scores were only reduced
      significantly at four weeks. In this group, interdental bleeding scores reduced
      significantly at four weeks (P = .028), but were not significantly different from
      baseline at eight weeks (P = .0319). When the two patient groups were compared
      using two sample t-tests, there were no significant differences in any of the
      parameters measured at any time point in the study. Over an eight-week period,
      there were no measurable differences between the powered toothbrush with modified
      orthodontic brush head and a manual toothbrush with respect to mean change in
      plaque, gingivitis, or interdental bleeding scores when used by patients wearing
      fixed appliances.

PMID- 11999937
TI  - Shear bond strengths of plastic brackets with a mechanical base.
AB  - This study compares the shear bond strengths of plastic brackets with a
      mechanical base and metal brackets using two different adhesives, and examines
      the modes of failure using a scanning electron microscope (SEM). Forty extracted
      human premolars were selected for bonding. Two types of brackets: metal and
      plastic-Spirit MB, and two orthodontic adhesives: System 1 + and Enlight, were
      used. After bonding, all samples were put into a 37 degrees C distilled water
      bath for 24 hours before shear bond strengths were tested. The bond strengths of
      the plastic brackets were significantly lower than those of the metal brackets (P
      < .0001). There was a statistically significant difference in bond strengths
      between System 1 + and Enlight for plastic brackets (P < .05), but not for metal
      brackets. The modes of failure predominantly occurred at the enamel/adhesive
      interface in the metal bracket-System 1 + group, within the adhesive in the metal
      bracket-Enlight and plastic bracket-System 1 + groups, and at the
      bracket/adhesive interface in the plastic bracket-Enlight group.

PMID- 11999938
TI  - Prevalence of temporomandibular dysfunction and its association with malocclusion
      in children and adolescents: an epidemiologic study related to specified stages
      of dental development.
AB  - A sample of 4724 children (2353 girls and 2371 boys) (5-17 years old) were
      grouped not only by chronological age but also by stage of dental development
      (deciduous, early mixed, late mixed, and permanent dentition). The registrations
      included functional occlusion (anterior and lateral sliding, interferences),
      dental wear, mandibular mobility (maximal opening, deflection), and
      temporomandibular joint and muscular pain recorded by palpation. Headache was the
      only symptom of temporomandibular dysfunction (TMD) reported by the children. The
      results showed that one or more clinical signs were recorded in 25% of the
      subjects, most of them being mild in character. The prevalences increased during
      the developmental stages. Girls were in general more affected than boys.
      Significant associations were found between different signs, and TMD was
      associated with posterior crossbite, anterior open bite, Angle Class III
      malocclusion, and extreme maxillary overjet.

PMID- 11999939
TI  - Relationships between dental calcification stages and skeletal maturity
      indicators in Thai individuals.
AB  - The purpose of this study was to investigate the relationship between the stages
      of calcification of various teeth and skeletal maturity stages among Thai
      individuals. The study subjects consisted 139 male subjects and 222 female
      subjects ranging in age from 7 years to 19 years. A total of 361 hand-wrist and
      panoramic radiographs were obtained and analyzed. The tooth development of the
      mandibular canines, first and second premolars, and second and third molars were
      assessed according to the Demirjian's system. Skeletal age and skeletal maturity
      stages were determined from hand-wrist radiographs by using the method outlined
      in the atlas of Greulich and Pyle and the Fishman's system, respectively. The
      Spearman rank order correlation coefficient revealed significant relationships (r
      = 0.31-0.69, P < .01) between dental calcification stages and skeletal maturity
      stages. The second premolar was the tooth showing the highest correlation (r =
      0.66 in male subjects, r = 0.69 female subjects). The third molar demonstrated
      the poorest correlation (r = 0.47 in male subjects, r = 0.31 in female subjects).
      The canine stage F for both sexes (63.2% for female subjects, 54.1% for male
      subjects) coincided with the MP3 stage. The second molar stage E for female
      subjects (51.4%) and stage G for male subjects (66.7%) were related to the S
      stage and the MP(3cap) stage, respectively. This suggests that tooth
      calcification stages from panoramic radiographs might be clinically useful as a
      maturity indicator of the pubertal growth period. However, further study is
      recommended in a larger sample size, and future studies should address
      development of the canines and second molars.

PMID- 11999940
TI  - Unilateral distal molar movement with an implant-supported distal jet appliance.
AB  - With the guidance of the basis of the distal jet appliance, we present a new
      implant-supported distal jet appliance. In this case, we used a modified distal
      jet appliance that was supported by a palatal implant placed at the anterior edge
      of the rugae region of the palate for molar distalization. The treatment results
      were evaluated from lateral cephalometric and panoramic radiographs and dental
      casts. We conclude that an implant-supported modified distal jet appliance is
      effective in the correction of a Class II molar relationship.

PMID- 11999941
TI  - Orthodontically induced inflammatory root resorption. Part I: The basic science
      aspects.
AB  - Orthodontically induced inflammatory root resorption (OIIRR) or, as it is better
      known, root resorption, is an unavoidable pathologic consequence of orthodontic
      tooth movement. It is a certain adverse effect of an otherwise predictable force
      application. Although it is rarely serious, it is a devastating event when it is
      radiographically recognized. Orthodontics is probably the only dental specialty
      that actually uses the inflammatory process as a means of solving functional and
      esthetic problems. Force application initiates a sequential cellular process. We
      know exactly how and when it is evoked, but we are unable to predict its actual
      overall outcome. The extent of this inflammatory process depends on many factors
      such as the virulence or aggressiveness of the different resorbing cells, as well
      as the vulnerability and sensitivity of the tissues involved. Individual
      variation and susceptibility, which are related to this process, remain beyond
      our understanding. We are therefore unable to predict the incidence and extent of
      OIIRR after force application. This contemporary review is divided into two
      parts. In Part I, we discuss the basic sciences aspects of OIIRR as a
      continuation of our previously published work. In Part II, we present the
      clinical aspects of this subject.

PMID- 11999942
TI  - Orthodontically induced inflammatory root resorption. Part II: The clinical
      aspects.
AB  - Over the past 10 years, orthodontically induced inflammatory root resorption
      (OIIRR) has been increasingly recognized as an iatrogenic consequence of
      orthodontic treatment. With this in mind, orthodontists should take all known
      measures to reduce the occurrence of OIIRR. The evidence that we present in this
      review suggests several procedures known today that can avert this phenomenon;
      however, none of them can be relied on to completely prevent OIIRR. We believe
      that future studies might clarify the exact cause and course of OIIRR and,
      hopefully, help eliminate it. In Part I, we discussed the basic sciences aspects
      of OIIRR; in Part II, we present the clinical aspects of this phenomenon.

PMID- 11999943
TI  - Does the canine dental follicle cause resorption of permanent incisor roots? A
      computed tomographic study of erupting maxillary canines.
AB  - We performed computed tomography (CT) on 107 children and adolescents aged 9-15
      years with 176 unerupted maxillary canines (152 erupting ectopically and 24
      erupting normally) to determine whether there is an association between widened
      dental follicles of the maxillary canines and resorption of the adjacent incisors
      during eruption. Contiguous axial (transverse) CT scans were obtained through the
      maxilla in the region of the canines. The width and shape of the dental follicles
      were recorded, as were any contacts between the follicles and the crowns of the
      maxillary canines and neighboring incisors. Fifty-eight lateral incisors (38%)
      and 14 central incisors (9%) had some type of root resorption. The position of
      the maxillary canine in relation to the root of the lateral incisor varied
      greatly, as did the width and shape of the canine dental follicle. Follicle width
      ranged from 0.5 mm to 7.0 mm. The mean +/- SD width of dental follicles was, on
      average, larger for the ectopically positioned canines (2.9 +/- 0.8 mm) than for
      the normally erupting canines (2.5 +/- 0.8 mm) (P < or = .01). We found that
      during eruption, the follicle of the erupting maxillary canine frequently
      resorbed the periodontal contours of adjacent permanent teeth but not the hard
      tissues of the roots. We concluded that the dental follicle did not cause root
      resorption of permanent teeth. Resorption of neighboring permanent teeth during
      maxillary canine eruption was most probably an effect of the physical contacts
      between the erupting canine and the adjacent tooth, active pressure during
      eruption, and cellular activities in the tissues at the contact points, all of
      which are part of the eruptive mechanism. The findings also confirm an
      association between root resorption of deciduous canines and the dental follicles
      of erupting permanent canines.

PMID- 11999944
TI  - Advances in FDG PET probes in surgical oncology.
AB  - Whole-body positron emission tomography (WB-PET) has been developed as a
      sensitive, cost-effective method for imaging malignant disease. WB-PET provides
      complete body imaging with a single scanning approach for a variety of
      malignancies. With increasing clinical experience, the indications for its use
      have broadened. This article reviews current uses of the technology and discusses
      some potential applications, particularly the utility of a commercially available
      surgical gamma probe for detecting the gamma particles emitted in the decay
      process of FDG.

PMID- 11999945
TI  - Special techniques for imaging blood flow to tumors.
AB  - In this review, the current imaging methods of assessing tumor perfusion are
      discussed and compared. Because most of the techniques depend on the
      administration of contrast agents, we first consider some general principles
      underlying the fate of contrast agents and their behavior inside the unique
      vascular environment of tumors.

PMID- 11999946
TI  - PET scanning and measuring the impact of treatment.
AB  - Positron emission tomography (PET) scanning with F18-fluorodeoxyglucose or FDG is
      a becoming a standard method for tumor staging. The prediction and evaluation of
      therapy response are newer applications of FDG-PET. PET often offers an early
      readout of treatment efficacy and is an attractive alternative to conventional
      anatomic assessments of treatment response. This article reviews the methods
      available with PET to monitor therapy response. Disease specific applications of
      PET imaging are then reviewed. While FDG is the most commonly used radiotracer
      for PET, many other radioligands could be applied in the future.

PMID- 11999947
TI  - Polymerase chain reaction in the staging of solid tumors.
AB  - Polymerasechain reaction (PCR) is a molecular biology technique that holds great
      promise as a way to perform molecular staging of cancer by detecting very early
      metastatic disease. Significant data suggest that PCR analysis may play an
      important role in the management of colorectal cancer in the future. However, for
      PCR staging of breast cancer, progress awaits identification of gene markers that
      have sufficient sensitivity and specificity. Within the next few years, the
      results of the Sunbelt Melanoma Trial and other ongoing studies will determine
      whether PCR evaluation of sentinel lymph nodes and peripheral blood cells has
      prognostic relevance in melanoma. The future of cancer management will likely
      revolve around the molecular staging of tumors, and PCR is but one method that
      may better define subgroups of patients that are appropriate candidates
      forvarious anticancer therapies.

PMID- 11999948
TI  - Hand-assisted laparoscopic surgery for cancer.
AB  - Minimally invasive surgical approaches were designed to enhance quality of care
      and improve patient outcome by minimizing postoperative pain, shortening hospital
      stay, reducing costs, and facilitating early return to work and presurgical
      lifestyle. The hand-assisted laparoscopic approach for resection of cancer is
      still in its formative stage, and this review places it in proper perspective
      within the context of minimally invasive surgery currently being performed for
      both benign and malignant disease. The review also outlines the potential
      advantages and disadvantages, techniques, and site-specific procedures of hand
      assisted laparoscopic surgery for cancer.

PMID- 11999949
TI  - New technology for deep light distribution in tissue for phototherapy.
AB  - Photodynamic therapy is one of several techniques developed for phototherapy for
      solid cancers and hematologic malignancies. Photodynamic therapy is a treatment
      that utilizes a molecular energy exchange between visible light and a
      photosensitive drug, which results in the production of 1O2, a highly reactive
      cytocidal oxygen species. The effect is limited to the region where light and
      drug are combined so that malignant tissue is destroyed and the usual side
      effects associated with standard cancer therapies are avoided. The light
      component of photodynamic therapy is customarily generated via dye-pumped or
      diode lasers. The cost and the complexity of lasers have seriously limited the
      clinical use of photodynamic therapy for malignancies. A new device technology,
      based on light-emitting diodes, has been developed (Light Sciences Corporation,
      Issaquah, WA) that allows light production inside the target tissue. This new
      technology will expand the current range of indications that are treatable with
      photodynamic therapy to include moderate- and large-volume refractorytumors.
      Conventional photodynamic therapy utilizes the delivery of intense light for
      seconds or minutes. The new approach differs from conventional photodynamic
      therapy in that it combines a novel interstitial light delivery system with
      prolonged photoactivation of photosensitive drugs. Prolonging photoactivation
      time in order to deliver a higher light dose results in an amplification effect,
      whereby the repeated activation of each photosensitive drug molecule leads to the
      generation of many thousands of 1O2 molecules. The production of overwhelming
      numbers of these powerful oxidants in individual cells and the vascular supply of
      tumors leads to irreversible damage and death of the targeted lesions. Results of
      preclinical studies have indicated a significant correlation between increased
      duration of photoactivation and increased volume and depth of photodynamic
      therapy-induced necrosis. The new developments will enable photodynamic therapy
      to be used effectively against refractory bulky disease as frontline therapy or
      in combination with chemotherapy, radiation therapy, or biologics. Perhaps most
      promising, many patients with advanced refractory disease may now be relieved of
      symptoms or may return to the treatable population.

PMID- 11999950
TI  - Radiofrequency ablation of early-stage invasive breast tumors: an overview.
AB  - As the management of breast cancer evolves toward less invasive treatments, the
      next step is the possibility of removing the primary tumor without surgery. The
      most promising of the noninvasive ablation techniques is radiofrequency ablation,
      which uses frictional heating that is caused when ions in the tissue attempt to
      follow the changing directions of a high-frequency alternating current. Three
      pilot studies, including an ongoing study at M.D. Anderson Cancer Center, have
      demonstrated that radiofrequency ablation is effective for the destruction of
      small primary breast cancers. The most important factorfor successful
      radiofrequency ablation is accuracy of the ultrasound evaluation, which is used
      to estimate tumor size, localize the tumor for treatment, and monitor the
      progress of the ablation. A study in preparation at M.D. Anderson will determine
      whether the use of radiofrequency ablation alone for the local treatment of
      primary breast cancer will result in outcomes equivalent to those obtained with
      breast conservation therapy.

PMID- 11999951
TI  - Percutaneous vertebroplasty in the treatment of malignant spine disease.
AB  - Percutaneous vertebroplasty is a minimally invasive, radiologically-guided
      interventional procedure originally developed in France for the treatment of
      painful vertebral hemangiomas. The technique consists of the percutaneous
      puncture of the affected vertebral body, followed by injection of an acrylic
      polymer to provide bone augmentation and prevent further collapse. The internal
      "casting" of the trabecular microfractures results in pain relief and vertebral
      consolidation. Vertebroplasty was quickly adopted for use in metastatic vertebral
      lesions and hematologic malignancies such as multiple myeloma and lymphoma. The
      major experience with malignant disease has remained primarily in the European
      realm; in the United States vertebroplasty is used mainly for the treatment of
      osteoporotic compression fractures. The reasons underlying this divergence in
      practice experiences remains unclear, although the explosion of vertebroplasty in
      the U.S. appears to be driven by an assertive, motivated and well-informed
      elderly population. In addition, malignant lesions are often challenging and
      practitioners may shy away from these clinically and technically more difficult
      patients. The purpose of this article is to introduce the principles of
      percutaneous vertebroplasty to the North American oncologic community with the
      hope that it mayfind a greater role in the treatmentof malignant disease
      affecting the spine.

PMID- 11999952
TI  - Monitoring apoptosis in real time.
AB  - Many therapeutically active anticancer treatments exert their effect by the
      induction of apoptosis and necrosis. Serial biopsies in breast cancer patients
      have suggested that response to therapy correlates with early posttreatment
      increases in tumor apoptotic index. Radiolabeled technetium Tc 99m-recombinant
      human (rh) annexin V provides a noninvasive technique for imaging treatment
      induced cell death. Annexin V is a naturally occurring human protein that binds
      avidly to membrane-associated phosphatidylserine (PS). PS is normally found only
      on the inner leaflet of the cell membrane double layer, but it is actively
      transported to the outer layer as an early event in apoptosis and becomes
      available for annexin binding. Annexin also gains access to PS as a result of the
      membrane fragmentation associated with necrosis. In vitro studies of apoptosis
      using fluorescein annexin have shown good correlation with assessments of
      apoptosis documented by nuclear DNA degradation and caspase activation. In vivo
      localization of intravenously administered Tc 99m-annexin V has been demonstrated
      in numerous preclinical models of apoptosis, including anti-Fas-mediated hepatic
      apoptosis, rejection of allogeneic heterotopic cardiac allografts,
      cyclophosphamide treatment of murine lymphoma, cyclophosphamide-induced apoptosis
      in bone marrow, and leukocyte apoptosis associated with abscess formation.
      Scintigraphic studies in humans using Tc 99m-rh annexin V have demonstrated the
      feasibility of imaging cell death in acute myocardial infarction, in tumors with
      a high apoptotic index, and in response to anti-tumor chemotherapy of non-small
      cell lung cancer, small-cell lung cancer, breast cancer, lymphoma, and sarcoma.
      Increased localization of Tc 99m-rh annexin V within 1 to 3 days of chemotherapy
      has been noted in some, but not all, subjects with these tumors. To date, most
      subjects showing increased Tc 99m-rh annexin V uptake after the first course of
      chemotherapy have shown objective clinical responses. A single site study in 15
      subjects with 1-year follow-up has suggested that increased posttreatment Tc 99m
      rh annexin uptake is associated with improved time to progression of disease and
      survival time. In vivo imaging of cell death may have the potential to improve
      the treatment of cancer patients by allowing rapid, objective, patient-by-patient
      assessment of the efficacy of tumor cell killing.

PMID- 11999953
TI  - Computer-aided detection in oncologic imaging: screening mammography as a case
      study.
AB  - Accuracy of the imaging report is dependent on the observational and interpretive
      skills of the radiologist, which varies between observers. Over the past several
      decades, research programs have focused on the use of computer algorithms to
      address both the perception and the interpretation aspects of diagnostic imaging.
      Computer-based technology that analyzes images in order to detect features of
      disease is called computer-aided detection (CAD). This paper reviews the current
      status of CAD as used with screening mammography.

PMID- 11999954
TI  - Design of corrugated optical waveguide filters through a direct numerical
      solution of the coupled Gel'fand-Levitan-Marchenko integral equations.
AB  - Regarding the design problem of corrugated planar optical waveguide filters, a
      new numerical method is presented consisting of a direct numerical solution of
      the coupled Gel'fand-Levitan-Marchenko integral equations. This method, which
      uses leapfrogging in space and time, is exact in principle and avoids some
      difficulties encountered in previously derived analytical methods of solution.
      Straightforward numerical calculations permit the design of several classes of
      filters such as Butterworth, Chebyshev, Cauer (elliptic) and others, as presented
      in the paper. The accuracy of our proposed method of design is checked in several
      ways, mainly through the numerical solution of the corresponding direct
      scattering problem (Riccati differential equation).

PMID- 11999955
TI  - Phase and amplitude modulation of elliptic polarization states by nonabsorbing
      anisotropic elements: application to liquid-crystal devices.
AB  - We study the modulation of programmable birefringent devices when they are
      illuminated by elliptically polarized light. We apply the theory to liquid
      crystal display panels (LCDs). We consider the setups at the input and the output
      sides of the LCD as polarization-state generators (PSGs) or detectors (PSDs). We
      demonstrate that once the programmable birefringent device is described by a
      physical model, the amplitude and phase modulation depend only on the
      polarization state at the input of the device and on the output state detected
      behind it. This permits optimization of the modulation response only in terms of
      the input and the output states and the physical model of the device. The
      procedure to find the PSG and PSD configurations is detailed by using a
      geometrical interpretation of the states and the plates on the Poincare sphere.

PMID- 11999956
TI  - Analysis for the convergence problem of the plane-wave expansion method for
      photonic crystals.
AB  - The convergence feature of two types of plane-wave expansion methods commonly
      used for photonic crystals is analyzed. It is shown that the reason for the slow
      convergence of these plane-wave expansion methods is not the slow convergence of
      the Fourier series for the permittivity profile of the photonic crystal but the
      inappropriate formulation of the eigenproblem. A new formulation of the
      eigenproblem is presented to improve the convergence in the one-dimensional case.

PMID- 11999957
TI  - Simplified description of optical forces acting on a nanoparticle in the Gaussian
      standing wave.
AB  - We study the axial force acting on dielectric spherical particles smaller than
      the trapping wavelength that are placed in the Gaussian standing wave. We derive
      analytical formulas for immersed particles with relative refractive indices close
      to unity and compare them with the numerical results obtained by generalized
      Lorenz-Mie theory (GLMT). We show that the axial optical force depends
      periodically on the particle size and that the equilibrium position of the
      particle alternates between the standing-wave antinodes and nodes. For certain
      particle sizes, gradient forces from the neighboring antinodes cancel each other
      and disable particle confinement. Using the GLMT we compare maximum axial
      trapping forces provided by the Gaussian standing-wave trap (SWT) and single-beam
      trap (SBT) as a function of particle size, refractive index, and beam waist size.
      We show that the SWT produces axial forces at least ten times stronger and
      permits particle confinement in a wider range of refractive indices and beam
      waists compared with those of the SBT.

PMID- 11999958
TI  - Dipole statistics of discrete finite images: two visually motivated
      representation theorems.
AB  - A discrete finite image I is a function assigning colors to a finite, rectangular
      array of discrete pixels. A dipole is a triple, ((dR, dC), alpha, beta), where dR
      and dC are vertical and horizontal, integer-valued displacements and alpha and
      beta are colors. For any such dipole, D(I)((dR, dC), alpha, beta) gives the
      number of pixel pairs ((r1, c1), (r2, c2)) of I such that I[r1, c1] = alpha,
      I[r2, c2] = beta and (r2, c2) - (r1, c1) = (dR, dC). The function D(I) is called
      the dipole histogram of I. The information directly encoded by the image I is
      purely locational, in the sense that I assigns colors to locations in space. By
      contrast, the information directly encoded by D(I) is purely relational, in the
      sense that D(I) registers only the frequencies with which pairs of intensities
      stand in various spatial relations. Previously we showed that any discrete,
      finite image I is uniquely determined by D(I) [Vision Res. 40, 485 (2000)]. The
      visual relevance of dipole histogram representations is questionable, however,
      for at least two reasons: (1) Even when an image viewed by the eye nominally
      contains only a small number of discrete color values, photon noise and the
      random nature of photon absorption in photoreceptors imply that the effective
      neural image will contain a far greater (and unknown) range of values, and (2)
      D(I) is generally of much greater cardinality than I. First we introduce "soft"
      dipole representations, which forgo the perfect registration of intensity
      implicit in the definition of D(I), and show that such soft representations
      uniquely determine the images to which they correspond; then we demonstrate that
      there exists a relatively small dipole representation of any image. Specifically,
      we prove that for any discrete finite image I with N > 1 pixels, there always
      exists a restriction Q of D(I) (with the domain of Q dependent on I) of
      cardinality at most N - 1 sufficient to uniquely determine I, provided that one
      also knows N; thus there always exists a purely relational representation of I
      whose order of complexity is no greater than that of I itself.

PMID- 11999959
TI  - Monochromatic aberrations provide an odd-error cue to focus direction.
AB  - Monochromatic aberrations that exist in the human eye will cause differences in
      the appearance of the point-spread function (PSF) depending on whether there is
      positive or negative defocus. We establish whether it is possible to use these
      differences in the PSF to distinguish the direction of defocus. The monochromatic
      aberrations of eight subjects were measured with a Hartmann-Shack wave-front
      sensor. Subjects also performed a forced-choice psychophysical task in which they
      decided whether a blurred target was defocused in front of or behind the retina.
      The optical system for the psychophysical task was designed to isolate the blur
      due to monochromatic aberrations as the only odd-error cue to the direction of
      defocus. Shack-Hartmann measurements showed that monochromatic aberrations
      increase as the pupil size increases. On average, the correct/incorrect responses
      for discriminating differences in the PSF for different directions of defocus
      were 54/46 for a 1-mm pupil and 83/17 for a 5-mm pupil, representing more than an
      eight-fold increase in discriminability. This discriminability extended for large
      amounts of defocus and also for more complex targets, such as letters.
      Sensitivity to the differences in the PSF for different directions of defocus
      increased as monochromatic aberrations increased, particularly for the even-order
      aberrations, which give rise to an odd-error focus cue. It was found that the
      ability to discriminate PSFs for different directions of defocus varied among
      individuals but, in general, depended on the magnitude of monochromatic
      aberrations.

PMID- 11999960
TI  - Spectral invariance under daylight illumination changes.
AB  - We develop a method for calculating invariant spectra of light reflected from
      surfaces under changing daylight illumination conditions. A necessary part of the
      method is representing the illuminant in a suitable form. We represent daylight
      by a function E(lambda, T) = h(lambda)exp[u(lambda)f(T)], where lambda is the
      wavelength, T is the color temperature, h(lambda) and u(lambda) are any functions
      of lambda but not T, and f(T) is any function of T but not lambda. We use an
      eigenvalue decomposition on the logarithm of the CIE daylight standard at various
      color temperatures to obtain the necessary functions and show that this gives an
      extremely good fit to CIE daylight over our experimental range. We obtain
      experimental data over the range 350-830 nm from a range of standard colored
      surfaces for 50 daylight conditions covering a wide range of illumination
      spectra. Despite a considerable variation in the spectra of the reflected light,
      we show only small variations when the transformation is used. We investigate the
      possible causes of the residual variation and conclude that using the above
      approximation to daylight is unlikely to be a major cause. Some variation is
      caused by local daylight conditions being different from the CIE standard and the
      rest by measurement and modeling errors.

PMID- 11999961
TI  - Extended Nijboer-Zernike approach for the computation of optical point-spread
      functions.
AB  - New Bessel-series representations for the calculation of the diffraction integral
      are presented yielding the point-spread function of the optical system, as occurs
      in the Nijboer-Zernike theory of aberrations. In this analysis one can allow an
      arbitrary aberration and a defocus part. The representations are presented in
      full detail for the cases of coma and astigmatism. The analysis leads to stably
      converging results in the case of large aberration or defocus values, while the
      applicability of the original Nijboer-Zernike theory is limited mainly to wave
      front deviations well below the value of one wavelength. Because of its intrinsic
      speed, the analysis is well suited to supplement or to replace numerical
      calculations that are currently used in the fields of (scanning) microscopy,
      lithography, and astronomy. In a companion paper [J. Opt. Soc. Am. A 19, 860
      (2002)], physical interpretations and applications in a lithographic context are
      presented, a convergence analysis is given, and a comparison is made with results
      obtained by using a numerical package.

PMID- 11999962
TI  - Assessment of an extended Nijboer-Zernike approach for the computation of optical
      point-spread functions.
AB  - We assess the validity of an extended Nijboer-Zernike approach [J. Opt. Soc. Am.
      A 19, 849 (2002)], based on ecently found Bessel-series representations of
      diffraction integrals comprising an arbitrary aberration and a defocus part, for
      the computation of optical point-spread functions of circular, aberrated optical
      systems. These new series representations yield a flexible means to compute
      optical point-spread functions, both accurately and efficiently, under defocus
      and aberration conditions that seem to cover almost all cases of practical
      interest. Because of the analytical nature of the formulas, there are no
      discretization effects limiting the accuracy, as opposed to the more commonly
      used numerical packages based on strictly numerical integration methods. Instead,
      we have an easily managed criterion, expressed in the number of terms to be
      included in the Bessel-series representations, guaranteeing the desired accuracy.
      For this reason, the analytical method can also serve as a calibration tool for
      the numerically based methods. The analysis is not limited to pointlike objects
      but can also be used for extended objects under various illumination conditions.
      The calculation schemes are simple and permit one to trace the relative strength
      of the various interfering complex-amplitude terms that contribute to the final
      image intensity function.

PMID- 11999963
TI  - Rigorous electromagnetic analysis of dipole emission in periodically corrugated
      layers: the grating-assisted resonant-cavity light-emitting diode.
AB  - We study the grating-assisted light-emitting diode, an LED design for high
      brightness based on a resonant cavity containing one- or two-dimensionally
      periodically corrugated layers (grating). We give in detail a generally
      applicable electromagnetic analysis based on the rigorous coupled-wave theory to
      calculate the extraction efficiency of spontaneous emission in a periodically
      corrugated layer structure. This general model is then specified on the grating
      assisted resonant-cavity LED, showing simulated efficiencies of more than 40%.

PMID- 11999964
TI  - Discrete dipole moment method for calculation of the T matrix for nonspherical
      particles.
AB  - A computational method, based on a moment solution to the discrete dipole
      approximation (DDA) interaction equations, is proposed for calculation of the T
      matrix of arbitrary-shaped particles. It is shown that the method will
      automatically provide the conservation-of-energy and origin-invariance properties
      required of the T matrix. Furthermore, the method is significantly faster than a
      T-matrix calculation by direct inversion of the DDA equations. Because the method
      retains the dipole lattice representation of the particle, it can be applied with
      relative ease to particles with irregular shapes-although in the same respect it
      will not automatically simplify for axisymmetric particles. Calculations of
      scattering matrix distributions, in fixed and random orientations, are made for
      tetrahedron, cylindrical, and prolate spheroid particle shapes and compared with
      DDA and extended boundary condition method results.

PMID- 11999965
TI  - New and fast calculation for incoherent multiple scattering.
AB  - To model bidirectional measurements, a numerical method for computing the
      incoherent light scattered by a diffusing medium is presented. The results are
      expressed as a function of the incident and the observer angles (theta(i),
      phi(i)) and (theta(f), phi(f)), in contrast to the N-flux method, which gives no
      information about the azimuthal-distribution. To solve the multiple-scattering
      equations, an auxiliary function, expanded on the spherical harmonics, is
      introduced in the diffusion equation. A set of integral equations on the
      coefficients are obtained that are well suited for the numerical resolution. The
      boundary conditions are included in the linear operator of the integral equation,
      so that each boundary condition is associated with a specific equation. As an
      illustration, the method is applied to numerical simulations of maps of the light
      scattered by a thick refractive diffusing layer of refractive index n = 1.5, for
      two directive phase functions and for several incident collimated-beam angles.

PMID- 11999966
TI  - Light scattering from self-affine fractal silver surfaces with nanoscale cutoff:
      far-field and near-field calculations.
AB  - We study the light scattered from randomly rough, one-dimensional, self-affine
      fractal silver surfaces with nanoscale lower cutoff illuminated by s- or p
      polarized Gaussian beams a few micrometers wide. By means of rigorous numerical
      calculations based on the Green's theorem integral equation formulation (GTIEF),
      we obtain both the far- and near-field scattered intensities. The influence of
      diminishing the size of the fractal lower-scale irregularities (from
      approximately 50 nm to a few nanometers) is analyzed in the case of both single
      realization and ensemble-average magnitudes. For s polarization, variations are
      small in the far field, being significant only in the higher-spatial-frequency
      components of evanescent character in the near field. In the case of p
      polarization, however, the nanoscale cutoff has remarkable effects stemming from
      the roughness-induced excitation of surface-plasmon polaritons. In the far field,
      the effect is noticed both in the speckle pattern variation and in the decrease
      of the total reflected energy upon ensemble averaging, as a result of increased
      absorption. In the near field, more efficient excitation of localized optical
      modes is achieved with smaller cutoff, which in turn leads to huge surface
      electric field enhancements.

PMID- 11999967
TI  - Analysis of modes and behavior of a multiconjugate adaptive optics system.
AB  - We study the so-called three-dimensional mapping of turbulence, a method solving
      the cone effect (or focus anisoplanatism) by using multiple laser guide stars
      (LGSs). This method also permits a widening of the corrected field of view much
      beyond the isoplanatic field. Multiple deformable mirrors, conjugated to planes
      at chosen altitudes among the turbulent layers, are used to correct in real time
      the wave fronts measured from the LGSs. We construct an interaction matrix
      describing the multiconjugate adaptive optics system and analyze the eigenmodes
      of the system. We show that the global tilt mode is singular because it cannot be
      localized in altitude, so that it must be corrected only once at any altitude.
      Furthermore, when the tilt from the LGS cannot be measured, the singularity of
      the global tilt yields the delocalization of particular forms of defocus and
      astigmatism. This imposes the use of a single natural guide star located anywhere
      in the corrected field to measure these modes. We show as an example that the
      cone effect can be corrected with a Strehl of 0.8 with four LGSs (tilt ignored)
      on an 8-m telescope in the visible when a single laser star provides a Strehl of
      0.1. The maximum field of view of 100 arc sec in diameter can be reconstructed
      with an on-axis Strehl ratio of 30%. We also show that the measurement of the
      height of the layers can be done with current techniques and that additional
      layers, not accounted for, do not significantly degrade the performance in the
      configuration that we model.

PMID- 11999968
TI  - Closed-loop stable control of two deformable mirrors for compensation of
      amplitude and phase fluctuations.
AB  - A method for closed-loop stable control of two deformable mirrors for
      compensation of both amplitude and phase fluctuations is described. A generic
      implementation is described as well as an implementation that integrates the
      concept behind a point diffraction interferometer with a two-deformable-mirror
      system. The relationship of the closed-loop control algorithm to previously
      developed open-loop iterative algorithms is described. Simulation results are
      presented that indicate that the system is stable and provides superior
      performance over that of a single-deformable-mirror system. The impact of finite
      servo bandwidth on control of two deformable mirrors is evaluated by means of
      wave optical simulation, and it is found that to achieve a performance
      improvement attributable to compensation of amplitude fluctuations, the bandwidth
      of the two-deformable-mirror system must be at least twice the Greenwood
      frequency.

PMID- 11999969
TI  - Fundamental radar properties: hidden variables in space-time.
AB  - A derivation of the properties of pulsed radiative imaging systems is presented
      with examples drawn from conventional, synthetic aperture, and interferometric
      radar. A geometric construction of the space and time components of a radar
      observation yields a simple underlying structural equivalence among many of the
      properties of radar, including resolution, range ambiguity, azimuth aliasing,
      signal strength, speckle, layover, Doppler shifts, obliquity and slant range
      resolution, finite antenna size, atmospheric delays, and beam- and pulse-limited
      configurations. The same simple structure is shown to account for many
      interferometric properties of radar: height resolution, image decorrelation,
      surface velocity detection, and surface deformation measurement. What emerges is
      a simple, unified description of the complex phenomena of radar observations. The
      formulation comes from fundamental physical concepts in relativistic field
      theory, of which the essential elements are presented. In the terminology of
      physics, radar properties are projections of hidden variables--curved worldlines
      from a broken symmetry in Minkowski space-time--onto a time-serial receiver.

PMID- 11999970
TI  - Simple approximate formula for the reflection function of a homogeneous, semi
      infinite turbid medium.
AB  - A simple, approximate analytical formula is proposed for the reflection function
      of a semi-infinite, homogeneous particulate layer. It is assumed that the zenith
      angle of the viewing direction is equal to zero (thus corresponding to the case
      of nadir observations), whereas the light incidence direction is arbitrary. The
      formula yields accurate results for incidence-zenith angles less than
      approximately 85 degrees and can be useful in analyzing satellite nadir
      observations of optically thick clouds.

PMID- 11999971
TI  - Signal-to-noise-ratio expressions in optical diffusion tomography.
AB  - Optical diffusion tomography is a technology that is employed to obtain images of
      the heterogeneous nature of turbid media by using optical radiation. Noise
      ultimately limits the achievable spatial resolution in these reconstructed
      images; therefore it is of interest to develop signal-to-noise-ratio expressions
      that relate spatial resolution in the images to the underlying system and
      material properties. In this study, Fourier-domain signal-to-noise-ratio
      expressions are derived for two types of optical diffusion tomography systems:
      those that use amplitude-modulated illumination sources and those that use
      continuous-wave illumination sources. The signal-to-noise-ratio expressions are
      compared for these two types of systems and are validated by laboratory data.

PMID- 11999972
TI  - Spatiospectral transmission of a plane-mirror Fabry-Perot interferometer with
      nonuniform finite-size diffraction beam illuminations.
AB  - The transmission of a plane-mirror Fabry-Perot (PFP) interferometer is
      theoretically modeled and investigated by treating the spatial and spectral
      features in a unified manner. A spatiospectral transfer function is formulated
      and utilized to describe the beam propagation and the multiple-beam interference
      occurring in an ideal one-dimensional strip PFP interferometer with no
      diffraction loss. The spatial-frequency filtration of a finite-size beam input
      not only determines the transmitted spatial beam profile but also plays a crucial
      role in affecting the overall spectral transmittance. The inherent deviations of
      the spectral transmittance from what we know as the standard Airy's formula are
      revealed in diverse aspects, including the less-than-unity peak transmittance,
      the displacement of a resonance peak frequency, and the asymmetric detuning
      profile. Our theoretical analysis extends to the misaligned PFP interferometers,
      such as the cases in which non-normal-incidence beams or wedge-aligned mirrors
      are used that could severely degrade the effective interferometer finesse.

PMID- 11999973
TI  - Geometrical setting for the classification of multilayers.
AB  - We elaborate on the consequences of the factorization of the transfer matrix of
      any lossless multilayer in terms of three basic matrices of simple
      interpretation. By considering the bilinear transformation that this transfer
      matrix induces in the complex plane, we introduce the concept of multilayer
      transfer function and study its properties in the unit disk. In this geometrical
      setting, our factorization translates into three actions that can be viewed as
      the basic components for understanding the multilayer behavior. Additionally, we
      introduce a simple trace criterion that allows us to classify multilayers into
      three types with properties closely related to one (and only one) of these three
      basic matrices. We apply this approach to analyze some practical examples that
      are typical of these types of matrices.

PMID- 11999974
TI  - Optimization approach to the suppression of vibration errors in phase-shifting
      interferometry.
AB  - An optimization-based strategy is introduced for suppressing errors due to
      vibration in phase-shifting-interferometry algorithms. A norm-square integral
      criterion of the error as a function of vibration frequency is used as the basis
      of the optimization procedure. Analytical results are obtained for certain
      classes of problems, and numerical algorithms are used when these are not
      available. It is also shown that the effect of vibration-induced errors in the
      computation of a time-averaged phase estimate diminishes as the measurements are
      averaged. Simulations are used to validate the analysis and demonstrate the
      overall efficacy of the approach. Generalizations to multiple objective
      optimization problems are briefly discussed.

PMID- 11999975
TI  - Plasma lysine concentration and availability of 2-ketoglutarate in liver
      mitochondria.
AB  - Defects of lysine metabolism are rare, but hyperlysinemia is a concomitant of
      many inborn errors of metabolism, including urea cycle abnormalities, pyruvate
      carboxylase deficiency and L-2-hydroxyglutaric aciduria. We have hypothesized
      that mitochondrial lysine degradation is regulated by bioavailability of 2
      oxoglutarate in the same compartment, and our studies in physiologic fluid
      derived from patients with the above described disorders supports our hypothsis.
      Our data further suggest that patients with isolated L-2-hydroxyglutaric aciduria
      may have a defect in 2-ketoglutarate metabolism. The current report summarizes
      our studies.

PMID- 11999976
TI  - Screening for carnitine palmitoyltransferase II deficiency by tandem mass
      spectrometry.
AB  - Mitochondrial carnitine palmitoyltransferase II (CPT II) deficiency is the most
      common inherited disorder of lipid metabolism in adults. Currently the routine
      diagnosis is based on the determination of CPT enzyme activity in muscle tissue.
      We have analysed the tandem mass spectra of serum acylcarnitines of nine CPT II
      deficient patients. These spectra were compared to those of a cohort of 99
      patients with other neuromuscular disorders and metabolic conditions supposed to
      cause alterations of the long-chain acylcarnitines. The spectra in CPT II
      deficiency showed characteristic elevations of C16:0 and C18:1 acylcarnitines
      while acetylcarnitine C2 was not elevated. In the present study, the ratio
      (C16:0+C18:1)/C2 has detected all CPT II deficiencies and discriminated them from
      unspecific alterations of serum acylcarnitines. The ratios of CPT II-deficient
      patients showed virtually no overlap with those observed in patients with other
      neuromuscular disorders. We suggest mass spectrometry of serum acylcarnitines as
      a rapid screening test that should be included early in the diagnostic work-up of
      patients with recurrent myoglobinuria, recurrent muscular weakness and myalgia.

PMID- 11999977
TI  - D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and
      unusual MRI findings.
AB  - We report an infant with intermittent urinary excretion of D-2-hydroxyglutaric (D
      2-OHG) acid who died at the age of 10 months from cardiogenic shock due to
      cardiomyopathy. High urinary concentrations of D-2-OHG and succinic acid, as well
      as increased levels of lactic acid were detected on three different occasions,
      whereas a normal urinary profile of organic acids was found on one occasion. The
      clinical findings of our patient consisted of generalized hypotonia,
      irritability, developmental delay, generalized tonic seizures, lethargy,
      cardiomyopathy, and respiratory distress. Cerebral MRI revealed bilateral lesions
      in the substantia nigra, the periaqueductal area, the medial part of the
      thalamus, the hypothalamus, the caudate nucleus, putamen and globus pallidus.
      This pattern is suggestive of a mitochondriopathy. However, respiratory chain
      enzyme activities were normal in fibroblasts. Exogenous supplementation of D-2
      OHG acid strongly inhibited cytochrome-c oxidase activity in fibroblasts from the
      patient and from normal controls in vitro. The results suggest that our patient
      has an unusual form of D-2-hydroxyglutaric aciduria (D-2-OHGA), different from
      the patients published so far, and that the increase of lactic acid and some
      citric acid cycle intermediates encountered in some patients with D-2-OHGA may be
      due to a functional defect of the respiratory chain caused by D-2-OHG acid.

PMID- 11999978
TI  - Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene
      in neonatal hypophosphatasia associated with convulsions.
AB  - We describe a patient diagnosed with lethal perinatal hypophosphatasia with a
      unique clinical presentation of convulsions that responded to vitamin B6. Genomic
      DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP)
      gene revealed two missense mutations: a G-to-A transition resulting in a Glu to
      Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at
      codon 309 (G309R). The first mutation was maternally transmitted and was
      previously characterized as a moderate one, whereas the latter was paternally
      transmitted and has not been previously reported. Phenotype/genotype correlation
      indicates that G309R is a deleterious mutation that can lead to seizures and a
      lethal outcome, as was demonstrated in our patient.

PMID- 11999979
TI  - Diagnosis of fructose-1,6-bisphosphatase deficiency using cultured lymphocyte
      fraction: a secure and noninvasive alternative to liver biopsy.
AB  - We report the result of enzymatic and molecular analyses, using cultured
      lymphocyte fractions (cultivated monocytes), of six Japanese patients (from five
      families) and one Italian patient with fructose-1,6-bisphosphatase (FBPase)
      deficiency. Enzymatic analysis demonstrated FBPase deficiency in all seven
      patients, including the Italian patient whose fructose-1,6-bisphosphatase
      activity has been reported to be normal in leukocytes but deficient in liver.
      Molecular analysis of the FBPase gene identified pathogenic mutations in only 8
      among the total 12 alleles of six families. We have thus demonstrated the
      validity of using cultured monocytes as a secure and noninvasive alternative to
      liver biopsy for accurate diagnosis of FBPase deficiency.

PMID- 11999980
TI  - Glycolipid analysis of different tissues and cerebrospinal fluid in type II
      Gaucher disease.
AB  - The lipid composition or the liver, spleen, brain, cerebellum and cerebrospinal
      fluid of a Gaucher disease type II patient who died at the age of 5 months was
      examined. The glycolipid analysis demonstrated a marked increase of total amounts
      not only in the peripheral tissues but also in the brain cerebellum and
      cerebrospinal fluid, with a prevalence of glucosylceramide. A reduction in
      gangliosides was observed in all the analysed tissues with a relative increase of
      GD3 in the nervous tissue. The fatty acid composition of glucosylceramide showed
      a prevalence of stearic acid in the central nervous system, while in the
      peripheral tissues palmitic acid was prevalent. This result suggests a different
      origin of the glucosylceramide stored in different tissues. The generalized
      reduction of gangliosides and their modified distribution together with the
      central nervous system GD3 increment represent a new observation. These data
      could be useful in the effort to clarify the pathophysiological mechanism of
      brain damage in neuronopathic Gaucher disease.

PMID- 11999981
TI  - Lipid status and long-chain polyunsaturated fatty acid concentrations in adults
      and adolescents with phenylketonuria on phenylalanine-restricted diet.
AB  - Blood lipid studies are reported in 25 adults and 2 adolescents with PKU who had
      been on phenylalanine-restricted diets for a mean period of 22.6 years (range 7
      39 years). Measurements included plasma concentrations of phenylalanine,
      cholesterol, lipoproteins, triglycerides and fatty acid profiles, including the
      analysis of seven fatty acids in plasma and red blood cells. Lipid screening
      identified 7 subjects with significantly elevated cholesterol/HDL ratios ranging
      from 5.6 to 10.3. Triglyceridaemia was documented in 5 of these 7, with
      concentrations ranging between 0.24 and 4.5 mmol/L (219-402 mg/dl) with a mean of
      3.5 mmol/L (310 mg/dl). The fatty acid analyses demonstrated slight but
      statistically significant reductions in the concentrations of long-chain
      polyunsaturated fatty acids (LCPUFA), including plasma docosahexaenoic (DHA) and
      arachidonic acid (AA), and red blood cell DHA concentrations. The pattern
      resembles that reported previously in children, but alterations in the mean
      levels are less severe. In six of the adult patients plasma DHA or AA
      concentrations were less than 50% of controls. Since DHA and AA have important
      physiological roles, including brain and retinal function, it is recommended that
      blood lipid concentrations be monitored in all patients with PKU, including
      adults, and that DHA and AA supplementation be provided, particularly in those
      patients in whom the blood concentrations of these substances are reduced
      significantly.

PMID- 11999982
TI  - Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review
      of molecular genetic findings.
AB  - We report two new patients with tetrahydrobiopterin (BH4)-responsive
      phenylketonuria and compare their phenylalanine hydroxylase (PAH) genotypes
      (A395P/ IVS12+g>a and R261Q/165T, respectively) to those of previous cases from
      the literature. These case observations confirm earlier reports stating that BH4
      responsive patients are frequently carriers of a missense mutation within the DNA
      region coding for the catalytic domain of the enzyme. Interestingly, many of the
      PAH gene mutations detected in BH4-responsive patients have been associated with
      an inconsistent phenotype in the past. Our case reports confirm that it is
      necessary to thoroughly examine individuals with increased phenylalanine levels,
      not only to detect BH4 deficiency, but also to identify patients with PAH
      deficiency who may benefit from BH4 treatment. In both of our patients, however,
      an effect of BH4 (7.5 mg/kg) on plasma phenylalanine levels was not seen in the
      newborn period. We therefore conclude that a normal neonatal BH4 test does not
      necessarily exclude BH4 responsiveness in all such patients.

PMID- 11999983
TI  - Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia
      detected by mass screening.
AB  - Type II citrullinaemia (CTLN2) is an adult- or late childhood-onset liver disease
      characterized by a liver-specific defect in argininosuccinate synthetase protein.
      The enzyme abnormality is caused by deficiency of the protein citrin, which is
      encoded by the SLC25A 13 gene. Until now, however, few cases with SLC25A13
      mutations have been reported in children with liver disease. We describe an
      infant who presented with neonatal hepatitis in association with
      hypergalactosaemia detected by neonatal mass screening. DNA analysis of SLC25A13
      revealed that the patient was homozygous for a IVS11+1G>A mutation. This case
      suggests that SLC25A13 mutant should be suspected in neonatal patients with
      hypergalactosaemia of unknown cause.

PMID- 11999984
TI  - Nasomaxillary hypoplasia and severe orofacial clefting in a child of a mother
      with phenylketonuria.
AB  - The offspring of mothers with untreated or poorly controlled phenylketonuria
      (PKU) (McKusick 261600) are at risk of having congenital anomalies including
      microcephaly, congenital heart defects and developmental delay (Rouse et al
      1997). We report a child born to a mother with poorly controlled PKU and suggest
      that the facial abnormalities seen in this child could be part of the specturn of
      maternal PKU embryopathy.

PMID- 11999985
TI  - Incidence of phenylketonuria in Iran estimated from consanguineous marriages.

PMID- 11999986
TI  - Removal of acetone and methylacetate mixtures from waste gases by a trickle-bed
      air biofilter.
AB  - The biofilter process is a relatively new technology that has been proven more
      cost-effective than traditional technologies for treating low-strength and some
      high-strength volatile organic compounds (VOCs) from waste gases. Acetone (AT)
      and methylacetate (MA) mixtures are commonly encountered from the manufacture of
      artificial rubber or polyurethane resin. This research attempts to employ a
      trickle-bed air biofilter (TBAB) for treating AT and MA mixtures under different
      influent carbon loadings. In the pseudo-steady-states, the elimination capacities
      of AT and MA increased but the removal efficiencies decreased with increased
      influent carbon loading. The removal efficiencies of MA were higher than those of
      AT showing that MA is a preferred substrate in the ATMA waste gas and the
      differences were enhanced at a high carbon loading. Greater than 95% AT removal
      and nearly complete MA removal were achieved with influent carbon loadings of AT
      and MA below 20 and 27 g m(-1) h(-1), respectively. The TBAB appears very
      efficient for treating ATMA emission with low to medium carbon loadings.

PMID- 11999987
TI  - Anti-fouling effect of bentonite suspension in ultrafiltration of oil/water
      emulsion.
AB  - The effect on membrane fouling resistance during ultrafilration of oil/water
      emulsion with the presence of bentonite suspension is experimentally evaluated.
      The fouling resistance was analyzed as a function of different membrane types and
      bentonite concentration. The total membrane fouling was categorized into
      reversible and irreversible, by adopting an appropriate chemical cleaning
      technique. The results revealed a 40% flux augmentation with the increase of
      bentonite concentration up to an optimum value of 300 mg l(-1) for cellulose
      acetate membrane. Further increase of bentonite concentration led to particle
      deposition on the membrane surface and reduced the flux. The polysulfone membrane
      did not show a similar flux improvement. This could be due to its high
      hydrophobicity. The absorption of oil/water emulsion on bentonite increased TOC
      removal rate from 65% to 80%, and this effect was the major cause of reduction in
      gel layer formation on the membrane surface. The extent of irreversible fouling
      of the hydrophilic cellulose acetate membrane was much smaller than that of the
      polysulfone membrane. These experiments demonstrated that, presence of bentonite
      could induce transformation of irreversible fouling caused by oil emulsion to
      reversible fouling, which could be periodically chemically cleaned.

PMID- 11999988
TI  - Use of leaching chambers for on-site sewage treatment.
AB  - An innovative chamber system was installed for on-site sewage treatment beneath
      an active parking lot at a restaurant near Cornwall, Ontario. The configuration
      of this prototype system used polyethylene leaching chambers over which
      wastewater was allowed to trickle. The chambers were vented to the surface to
      provide direct, passive air transfer. This demonstration project was examined as
      a cost-effective wastewater treatment alternative for a very constrained site.
      The leaching chambers were installed over a geotextile-covered sand filter bed.
      Chamber sidewall contact contributed an additional 50% to the total soil contact
      area hence justification for a footprint reduction. A labile carbon source
      (sawdust) was added into one half of the bed to encourage dissimilatory
      denitrification. Average hydraulic loading was 50 l m(-1) day(-1) (5 cm day(-1)).
      Treatment rates exceeded more than 4 orders of magnitude removal for E. coli; 90%
      biochemical oxygen demand; ammonium; and 99% total phosphorus. Nitrate-N on the
      carbon-amended side averaged 0.6 mg l(-1) compared with 8.6 mg l(-1) on the (non
      carbon) control side. This project has demonstrated that effective on-site
      treatment can be accomplished. Flow and load equalization, pulse dosing, chamber
      venting, phosphorus precipitation, and denitrification were keys to treatment
      success. Applications include domestic and commercial sites.

PMID- 11999989
TI  - Sensitivity analysis of stabilization pond system design parameters.
AB  - Two stabilization pond systems are examined. A sensitivity analysis is
      undertaken, aimed at investigating the influence of the pond depths on
      stabilization pond surface area and pond volume for the specific combination of
      temperature, wastewater characteristics and effluent requirements. The
      dependencies are presented in a functional form, allowing for the graphical
      solution of the unit pond volume, area, and hydraulic residence time as a
      function of the respective pond depths. Based on these graphs, designers can
      determine the most appropriate depth value for each type of pond that minimizes
      the required area or volume, or balances excavation versus land acquisition and
      floor lining costs, taking under consideration the topographic and other local
      characteristics of the site area.

PMID- 11999990
TI  - Assessment of the estrogenic activity of flue gases from burning processes by
      means of the yeast based human estrogen receptor (hER) bioassay.
AB  - Combustion processes are known to produce organic micro-pollutants in the flue
      gas at concentrations ranging over several orders of magnitude. Some organic
      micro-pollutants are suspected of being pseudo-estrogens and as such they can
      affect the public health. In this study, the possible application of the yeast
      based human estrogen receptor (hER) bioassay to screen flue gas streams for the
      presence of estrogenic active micro-pollutants was explored. Specifically, the
      protocol was modified to allow the detection and quantification of the potential
      estrogenic active non-polar organic micro-pollutants contained in the flue gas
      matrix. The modified assay was calibrated using a model estrogenic compound (17
      alpha-ethinylestradiol (EE2)) dissolved in methylene chloride at concentrations
      ranging from 3 ng l(-1) to 3000 ng l(-1). The effective concentration to
      elucidate a 50% response (EC50) was 87 ng l(-1) of equivalent dissolved in
      methylene chloride. Samples of methylene chloride used to trap non-polar micro
      pollutants in flue gas from combustion of pine wood were found to clearly
      register estrogenic activity by the bioassay under certain conditions. The
      combustion tests were performed with pinewood alone and with pine wood in the
      presence of both Copper-naphthenate and copper(II)chloride at 600 degrees C and
      1000 degrees C. These conditions must be considered as experimental rather than
      practical. Overall, the results suggest that, by means of this modified assay, it
      is possible and warranted to screen systematically for estrogens in flue gas
      combustion processes.

PMID- 11999991
TI  - Acidogenic fermentation: utilization of wasted sludge as a carbon source in the
      denitrification process.
AB  - Laboratory scale batch experiments were conducted at 20 degrees C to investigate
      the acidogenic fermentation for the conversion of wasted sludge into short chain
      fatty acids (SCFA) to be utilized as a carbon source in the denitrification
      process. Hydraulic retention time (HRT), volatile solid (VS) loading rate and pH
      were studied as these are the important parameters governing the production of
      volatile fatty acids (VFA). Four different phases were investigated by varying
      these parameters. HRT was varied from 2.7 to 8.2 days whereas VS loading rate was
      varied from 1.2 to 3.6 g d(-1). VFA production decreased with the increase in HRT
      above 2.7 days. 538.37+/-19.39 mg VFA(produced) x d(-1) (0.176+/-0.010 mg
      VFA(produced) mg(-1) VS(feed) was found as the maximum value of VFA at 2.7 days.
      The present results based on wasted sludge showed that almost 0.0483+/-0.0016 mg
      VFA (as COD mg(-1) initial COD) and about 5% of soluble COD production were
      achieved, which are slightly less than the results reported for primary sludges.
      The rates of VFA production increased with the increase in VS, however, opposite
      results were obtained when pH was increased in the reactor. SCFA/FA ratios during
      fermentation were found in the range of 67-73%. The specific denitrification
      rates (SDNR) of methanol (2.20+/-0.44 mg NO3-N g(-1) MLVSS x h(-1)) and the
      fermenter supernatant (2.00+/-0.45 mg NO3-N g(-1) MLVSS x h(-1)) were found to be
      comparable. Fermenter supernatant, therefore, has the potential to be utilized as
      a carbon source. However, the results need to be investigated further on a larger
      scale to ascertain their validity.

PMID- 11999992
TI  - Nitrification utilizing CaCO3 as the buffering agent.
AB  - Nitrification utilizing chalk (calcium carbonate) as the buffering agent was
      investigated. Three different fluidized bed reactor configurations were examined
      in order to study the effect of reactor layout on nitrification and concomitant
      chalk dissolution. The first system consisted of two interconnected columns with
      high recycle rate, one containing zeolite as the carrier for the nitrifying
      biomass and the other chalk as the buffering agent. The second reactor system
      consisted of a single column containing both zeolite and chalk particles. In the
      third system, nitrification was carried out in a single column where chalk
      particles were used both as the carrier for the biomass and as the buffer.
      Results showed that only the reactor with chalk acting as both the buffering
      agent and the biomass carrier could be operated without external buffer (NaHCO3)
      addition. This system operated at high ammonium removal rates of up to 2.5 g N l(
      1) reactor d(-1) even though the bulk solution of the reactor had a low pH of
      5.5. The high nitrification efficiency at this low pH was probably mainly a
      result of a favorable microenvironment surrounding the nitrifying biomass
      attached to the chalk.

PMID- 11999993
TI  - Biodegradation of toluene by a lab-scale biofilter inoculated with Pseudomonas
      putida DK-1.
AB  - The biodegradation of toluene by biofiltration inoculated with Pseudomonas putida
      DK-1 was investigated with variation of the several environmental parameters,
      such as temperature, bed length, gas flow rate and optimal humidity zone. The
      optimal temperature range to treat toluene gas was found to be 32-35 degrees C.
      Increasing the gas flow rate showed an inverse effect on the elimination capacity
      and the removal efficiency. The optimal gas flow rate was obtained at 65 ml min(
      1) from the relation between the removal efficiency and the elimination capacity.
      The biodegradation rate of the toluene with respect to the bed lengths (3, 6, 9,
      12 and 15 cm) increased up to 80 h but was then independent of the bed lengths
      after 80 h except for the 3 cm bed length. The elimination capacity was improved
      by about 70% compared with that reported in other literature and was also in
      agreement with theoretical models.

PMID- 11999994
TI  - Effectiveness of selected chemicals for controlling emission of malodorous sulfur
      gases in sewage sludge.
AB  - The effectiveness of various oxidants or redox buffers (ferric chloride, sodium
      hypochlorite, potassium permanganate, hydrogen peroxide and potassium nitrate)
      for controlling or reducing emission of reduced sulfur gases (hydrogen sulfide,
      carbonyl sulfide, methanethiol, dimethyl sulfide and carbon disulfide) produced
      from sewage sludge collected from a wastewater treatment plant was studied under
      laboratory conditions. Sludge was treated with 0, 30, 300 and 1000 ppm of each
      chemical and changes in emission of the various reduced sulfur gases were
      monitored over a period of 24 hours. Potassium permanganate and hydrogen peroxide
      were shown to be the best chemicals for reducing hydrogen sulfide (the dominant
      reduced sulfur gas measured) emission. Sodium hypochlorite was also effective in
      reducing hydrogen sulfide emission followed by the ferric chloride addition.
      Since considerably smaller quantities of other reduced sulfur gases were evolved,
      the influence of the various chemical additions were not as significant as the
      reduction observed for hydrogen sulfide emission. Potassium permanganate and
      hydrogen peroxide were effective in reducing methanethiol and dimethyl sulfide
      emission. To a lesser degree sodium hypochlorite and ferric chloride also reduced
      emission of these two reduced sulfur gases. Potassium nitrate had no effect on
      reducing hydrogen sulfide or any of the reduced sulfur gases over the 24 hour
      experimental period. Each of the chemicals used in the study had a little or no
      effect in reducing carbonyl sulfide and carbon disulfide emission from the sludge
      material.

PMID- 11999995
TI  - Construction of disturbed and intact soil blocks to develop percolating soil
      based treatment systems for dirty water from dairy farms.
AB  - Intact soil blocks with a surface area of 1.8 x 1.6 m, 1.0 m deep, were excavated
      in a coarse sandy loam. The sides of the soil blocks were supported with plywood
      before using hydraulic rams to force a steel cutting plate beneath them.
      Disturbed soil blocks of the same depth as the intact blocks were also
      established. Experiments were conducted to determine purification efficiencies
      for biological oxygen demand (BOD), molybdate reactive phosphorus (MRP), nitrate
      and ammonium-N after the application of dirty water. A preliminary experiment is
      described where a low application of dirty water was applied to the soil blocks,
      2 mm day(-1). In addition, a chloride tracer was conducted for the duration of
      the experiment. Disturbed soil had a purification efficiency for BOD of 99%
      compared to 96% from intact soil (P<0.001). Purification efficiencies for MRP and
      ammonium-N were 100 and 99%, respectively, for the intact and disturbed soils.
      Nitrate-N concentration increased in leachate from both treatments reaching
      maximum concentrations of 15 and 8 mg l(-1) from disturbed and intact soils,
      respectively. Chloride traces for each soil block followed similar patterns with
      47 and 51% loss from disturbed and intact soils, respectively.

PMID- 11999996
TI  - The use of waterworks sludge for the treatment of dye wastes.
AB  - Water treatment works using coagulation/flocculation in the process stream will
      generate a waste sludge. The works in Adana, Turkey uses ferric chloride. The
      potential for using this sludge for the treatment of reactive, direct, disperse,
      acidic, and basic dyestuffs by coagulation and sorption has been investigated.
      The sludge acted as a coagulant and removed colour with excellent removal
      efficiencies being obtained for basic, disperse and direct dyes. The optimum
      conditions were a pH value of 5 and a sludge dose of 2000 mg l(-1). Mediocre
      results were obtained for acidic and reactive dyes. The efficiency of the sludge
      was also compared with alum and ferric chloride for the same group of dyes. The
      sludge was also used as a coagulant to treat the wastewater from a textile
      factory. At doses of 2000-4000 mg l(-1), the sludge was as effective as ferric
      chloride and alum at removing COD. Sorption tests showed that the disperse and
      reactive dyes did not bind to the sludge. Langmuir and Freundlich constants were
      determined for the other three types of dye. Rate constants for the adsorption
      were determined using the Lagergren equation.

PMID- 11999997
TI  - Oxygen-limited nitrification and denitrification in a lab-scale rotating
      biological contactor.
AB  - Rotating Biological Contactors (RBC) treating highly nitrogenous wastewaters are
      known to give rise to nitrogen losses, generally assumed to be due to concomitant
      nitrification and denitrification. In this study, a lab-scale nitrifying RBC
      reactor was shown to bring about losses of nitrogen of the order of 10 to 20% at
      ammonium loading rates of up to 2129 mg N m(-2) d(-1), when no extra carbon
      source was added. These higher removal values could be due to Oxygen-Limited
      Autotrophic Nitrification and Denitrification (OLAND), because the reactor was
      operated at oxygen limitation. When methanol was added as a soluble organic
      carbon source to further diminish oxygen transfer into the deeper parts of the
      biofilm, the RBC achieved 84% nitrogen removal (loading rate 2300 mg N m(-2) d(
      1)) at a COD/N ratio of 3.1. The latter also suggests that the process was
      occurring parallel to conventional denitrification.

PMID- 11999998
TI  - Increased ozone-induced airway neutrophilic inflammation in extracellular
      superoxide dismutase null mice.
AB  - Extracellular-superoxide dismutase (EC-SOD) exists primarily in the tissue
      interstitium and the lung contains particularly large amounts of the enzyme. To
      determine the roles of EC-SOD and extracellularly formed superoxide radicals in
      the pulmonary response to the common air pollutant ozone, wild-type mice and mice
      lacking EC-SOD were exposed to 1.5 ppm ozone for 48 h. The exposure resulted in a
      marked neutrophilic inflammatory reaction observed both in the bronchoalveolar
      lavage fluid (BALF) and by histopathology of the lungs, which was much stronger
      in the mice lacking EC-SOD. Unlike the wild-type mice, the null mutants also
      showed increased levels of interleukin-6 in the BALF. The ozone exposure also
      resulted in increased airway mucosal permeability and cell damage as indicated by
      increased protein and lactate dehydrogenase in the BALF. There was, however, no
      difference between the two groups of mice.The results suggest that extracellular
      superoxide radicals are important inflammatory mediators in the pulmonary
      response to ozone, but in the present model, the radical and the infiltrating
      neutrophils contributed little to the pulmonary injury The data, together with
      previous findings, support a role for EC-SOD as a modulator of inflammatory
      reactions.

PMID- 11999999
TI  - Hyperthyroidism and pulmonary hypertension.
AB  - In recent years, many authors have described several cases revealing an
      association between hyperthyroidism and pulmonary hypertension (PH). This
      observational study was designed to evaluate the incidence of PH in
      hyperthyroidism and was set in a department of internal medicine and pulmonary
      diseases with an out-patients department of endocrinology. Thirty-four patients,
      25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty
      had Graves' disease and 14 had a nodular goitre. The patients were divided into
      two equally matched groups: those with a recently diagnosed hyperthyroidism,
      taking no drugs (group 1; n = 17) and those in a euthyroid state taking
      methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was
      performed and systolic pulmonary artery pressurements of (PAPs) was determined by
      the tricuspid regurgitation method using the Bernoulli equation. Measurements of
      triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating
      hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also
      taken. We found a mild PH in seven patients of group 1 and in none of group 2.
      The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1
      and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH
      value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in
      group 1. These findings indicate the presence of a frequent association between
      PH and hyperthyroidism. We suggest that hyperthyroidism be included in the
      differential diagnosis of PH.

PMID- 12000000
TI  - Safety, tolerability and acceptability of two dry powder inhalers in the
      administration of budesonide in steroid-treated asthmatic patients.
AB  - The purpose of this randomized, double-blind parallel group study was to compare
      the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder
      inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic
      patients who had already been treated with inhaled corticosteroids for at least 6
      months prior to the study Additionally the efficacy of the products was
      evaluated. The main objective was to evaluate the systemic safety of budesonide
      inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by
      serum and urine cortisol measurements. The secondary objective was to compare the
      tolerability acceptability and efficacy of the two devices in the administration
      of budesonide. After a 2-week run-in period (baseline), patients were randomized
      on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler
      (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two
      inhalations twice daily for 12 weeks. There was no statistically significant
      change in morning serum cortisol values from baseline to the end of treatment in
      either group. Urine free cortisol and urine cortisol/ creatinine ratio increased
      from baseline in both groups. There were no significant differences between the
      groups in terms of morning serum cortisol, urine cortisol, adverse events or
      efficacy variables, but Easyhaler was generally considered more acceptable to the
      patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and
      efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously
      treated with corticosteroids, but more acceptable to patients.

PMID- 12000001
TI  - Predictors of lung function in infants at high risk of atopy: effect of allergen
      avoidance.
AB  - Children of atopic parents are recognised as being at higher risk of developing
      bronchial asthma, drawing the attention of prevention strategies towards this
      population. Due to recent advances, lung function abnormalities in asthmatic
      children may now be measured early in life. The aim ofthis investigation was to
      examine possible predictors of lung function development in a sub sample of high
      risk infants who took part in an allergy avoidance study In 60 babies of atopic
      parents, measurements of upper airways inflammation were performed at 4 weeks of
      age, respiratory symptoms were assessed at 6 and 12 months of age, and lung
      function (Vmax, FRC) was measured at 18 months by the rapid thoracoabdominal
      compression technique. Twenty-eight babies were enrolled in an allergen avoidance
      program, and 32 recruited as controls. No significant differences were detected
      for V'max,FRC between the intervention group (mean 331 ml s(-1)) and the control
      group (359 ml s(-1)), P = 0.382. A multiple linear regression model could explain
      levels of V'max FRC by weight gain since birth (beta = -35.35 ml s(-1) kg(-1), P
      = 0.022) and by eosinophilic cationic protein (ECP) (beta = -0.95 ml s(-1)
      microl(-1), P = 0.044), but not by intervention. Lung function measured at the
      age of 18 months in high-risk children is associated with weight gain and nasal
      ECF.

PMID- 12000002
TI  - Diagnosis of flour-induced occupational asthma in a cross-sectional study.
AB  - The diagnosis of occupational asthma is usually performed in epidemiology using a
      combination of symptoms and bronchial hyperresponsiveness, while in a clinical
      setting the 'gold standard' for the diagnosis of occupational asthma is the
      specific bronchial challenge test in the laboratory The aim of this study was to
      detect new cases of flour-induced occupational asthma (OA) in a group of workers
      exposed to grain and/or flour dust, by means of a step-by-step approach, as used
      in a clinical setting. In an epidemiological study, III millers and 186 bakers
      were examined by means of questionnaire, pulmonary function tests and skin-prick
      tests (SPT) to common allergens and to wheat flour dust extracts. From the whole
      sample, 82 subjects who showed asthma-like symptoms in the questionnaire and/or
      low forced expiratory volume in 1 sec (FEV1) were selected. Selected subjects
      underwent methacholine challenge test, and hyperreactive subjects underwent
      specific bronchial challenge with flour dust in the laboratory. Sixty-two of the
      selected subjects performed the methacholine challenge test, and 22 (33 8%) were
      hyperreactive (PD20 FEV1 <1 mg of methacholine). Fifteen of 22 hyperreactive
      subjects underwent specific bronchial challenge test (s BCT) with flour dust; a
      positive response was elicited in six subjects. These subjects can be diagnosed
      as having flour-induced occupational asthma. Atopy and skin sensitivity to flour
      was partially related to the response to flour bronchial challenge. Bronchial
      hyperreactivity can be observed in a small percentage of subjects with asthma
      like symptoms and/or low FEV1, and a positive response to s BCTwas observed in a
      subgroup of hyperreactive subjects.Therefore, using these selection criteria, a
      diagnosis of flour-induced OA, as commonly performed in a clinical setting, can
      be performed in few previously undiagnosed subjects.This approach could be
      relevant for an early diagnosis ofoccupational asthma.

PMID- 12000003
TI  - In vitro expression of fas and CD40 and induction of apoptosis in human cystic
      fibrosis airway epithelial cells.
AB  - Cystic fibrosis is characterized by a damaged airway epithelium with inflammation
      and chronic infection. The aim of this study was to investigate the process of
      apoptosis in this disease. To evaluate the effects of interferon gamma and the
      Fas apoptotic pathway on cystic fibrosis airway epithelial cells, we used
      immortalized cystic fibrosis (CFT-1 and CFT-2) and normal (NT-1) human tracheal
      epithelial cell lines. Cell death was determined usingannexin-V/propidium iodide
      labelling and electron microscopy. In vitro expression of Fas and CD40 surface
      antigens was analysed by immunofluorescence staining and flow cytometry. Normal
      and cystic fibrosis cells constitutively express these antigens. CD40, but not
      Fas expression, was upregulated by interferon gamma. Treatment of interferon
      gamma-stimulated cells with anti-Fas resulted in apoptosis for about 80% of CFT-2
      (homozygous for delta F508 deletion) cells and for 35-40% of CFT-1 (heterozygous)
      or normal cells. Our results suggest that Fas may mediate apoptosis in cystic
      fibrosis airway epithelium.

PMID- 12000004
TI  - Cost-effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in
      children with symptomatic asthma.
AB  - We conducted an economic evaluation in a UK setting based on a 12-week
      prospective randomized open-label parallel-group comparison of eformoterol
      Turbohaler 12 microg b. i.d. with salmeterol Accuhaler 50 microg b. i.d. in
      children aged 6-17 with symptomatic asthma receiving inhaled corticosteroids and
      short-acting beta2-agonists. The principal effectiveness measure was percentage
      of symptom-free days with no short-acting beta2-agonist use during the study
      period. Asthma-related medication, unscheduled physician contacts and
      hospitalizations were collected prospectively and cost to the UK NHS calculated
      using year 2,000 prices. The economic evaluation included 73 patients in the
      eformoterol group and 72 patients in the salmeterol group. The mean age of
      patients was 11.6 years (eformoterol) and 11.8 years (salmeterol). The mean
      percentage of symptom-free days with no short-acting beta2-agonist use was 39% in
      the eformoterol group and 30% in the salmeterol group. Mean per patient daily
      cost was 1.15 pounds in the eformoterol group and 1.39 pounds in the salmeterol
      group. Both cost and effectiveness differences favoured eformoterol (P < 0.05;
      one-sided). Sensitivity analysis confirmed the results to be robust to changes in
      effectiveness, price and resource utilisation parameters. Eformoterol delivered
      by Turbohaler was found to be significantly more effective and less expensive
      than salmeterol Accuhaler in this study.

PMID- 12000005
TI  - Cytological examination of the whole endobronchial brush in bronchoscopic
      diagnosis of lung cancer.
AB  - The combination of cytological and histological techniques has significantly
      increased the accuracy of fibreoptic bronchoscopy (FOB) in the diagnosis of lung
      cancer. We tested the hypothesis that cytological examination of material
      obtained from the whole endobronchial brush might increase the diagnostic yield
      in patients where conventional brush specimens were negative. Fifty patients who
      had undergone FOB for suspected lung cancer were studied prospectively. Bronchial
      lavage, bronchial biopsy and conventional brushing were performed. The whole
      endobronchial brush was then cut off the end of its wire and transported in a
      universal pot containing Shandon cytospin collection fluid. The material was
      dislodged from the whole brush using a vortex and the remaining fluid was
      centrifuged at 2,000 r.p.m. The fluid concentrate was used to maketwo cytopsin
      preparations. Papanicolaou stain was used. Fifty patients were studied, of which
      thirty-nine (78%) had endoscopicaly visible tumour. Of those, bronchial biopsy
      conventional brushing lavage and whole brush were positive for malignant cells in
      31 (79.4%), 29 (74.3%), 21 (53.8%), and 16 (41%) of cases, respectively. A
      diagnosis of lung cancer was confirmed in 35 (89.7%) cases of endoscopicaly
      visible tumour. Conventional brushing was positive in two out of 11 (18.2%) cases
      with no visible tumour. Whole brush analysis was not positive in any of the cases
      with negative conventional brushings and was the least sensitive test in
      detecting malignancy Whole endobronchial brush analysis has no advantage in
      bronchoscopic diagnosis of patients with suspected lung cancer.

PMID- 12000006
TI  - Role of TNF-alpha and its 55 and 75 kDa receptors in bronchial hyperreactivity.
AB  - The pathophysiological role of the tumour necrosis factor (TNF) system was
      studied in adults (n=37) and children (n=43) non asthmatic offspring of asthmatic
      parents with and without bronchial hyperreactivity proved by methacholine airway
      challenge test. SerumTNFalpha and its soluble receptors (sTNF-R1 and R2) were
      determined by enzyme-linked immunosorbent assay (ELISA). Significantly elevated
      TNFalpha (adults: mean +/- SD=5.18 +/- 0.87 pg ml(-1), children: 5.08 +/- 1.78)
      vs. non-hyperreactives (adults: 4.12 +/- 0.43, P < 0.0001, children: 3.75 +/-
      0.68, P=0.0084), sTNF-R1 (adults: 144 +/- 0.31 ng ml(-1), children: 1.30 +/- 0 25
      vs. adults: 1.21 +/- 0.14, P=0.0305, children: 1.13+/-0.11 ng ml(-1), P=0.0042)
      and sTNF-R2 (adults: 0.85 +/- 0.40ng ml(-1), children: 0.70 +/- 0.46 vs. adults:
      0.56 +/- 0.56 P=0.0084, children: 0.33 +/- 0.17, P=0.0048) and decreased sTNF
      R1/R2 ratio (adults: mean +/- SD=0.96 +/- 0.73, children: 2.85 +/- 2.06 vs.
      adults: 4.82+/-3.40, P=0.0272, children: 4 42 +/- 2 30, P=0.0167) were measured
      in patients with bronchial hyperreactivityThe provocation doses of methacholine
      causing a 20% reduction (PD20) in forced expiratory volume in 1 sec (FEV1) were
      found to be in a significant negative linear correlation with TNFalpha sTNF-R1
      and R2 levels in hyperreactive adults and with TNFalpha, sTNF-R2 in hyperreactive
      children. TNFalpha correlated significantly with its receptors both in
      hyperreactive adults and children and with the body mass index (BMI) values of
      adults. The TNF system may contribute to the pathophysiology of bronchial
      hyperreactivity Altered shedding of sTNF-R1 seems to occur in hyperreactive
      patients.

PMID- 12000007
TI  - Respiratory system mechanics during laparoscopic cholecystectomy.
AB  - The influence of laparoscopic cholecystectomy (LC) on the mechanical properties
      of the respiratory system (RS) was examined using multiple regression analysis
      (MRA). Measurements of airway pressure (PaO) and flow (V') were obtained from 32
      patients at four distinct stages of the LC procedure: 1) Immediately before the
      application of pneumoperitoneum (PP) at supine position, 2) 5 min after the
      induction of PP at Trendelenburg position, 3) 5 min after the patients position
      at reverse Trendelenburg, and 4) 5 min after the end ofthe surgical procedure
      with the patient again in supine position. Evaluated parameters were the RS
      elastance (Ers), resistance (Rrs), impedance (Zrs), the angle theta indicating
      the balance between the elastic and resistive components of the impedance, as
      well as the end-expiratory elastic recoil pressure (EEP). Ers and Zrs increased
      considerably during PP and remained elevated immediately after abolishing PP Rrs,
      on the contrary, returned to pre-operative levels right after the operation.
      Change of body position from Trendelenburg (T) to reverseTrendelenburg (rT)
      mainly induced a significant change in theta, thus indicating an increased
      dominance of the elastic component of Zrs on changing fromT to rT. There was no
      evidence of increased End-Expiratory Pressure during PP

PMID- 12000008
TI  - The inhibition of pro-inflammatory cytokines with pentoxifylline in the
      cardiopulmunary bypass lung.
AB  - In addition to preventing tissue energy loss during cardiopulmonary bypass,
      pentoxifylline (Ptx) prevents the production of pro-inflammatory cytokines as
      well. The aim of this study was to investigate whether Ptx decreases the
      inflammatory effects of cardiopulmonary bypass on the lungs during open-heart
      surgery. The patients in the study group (n = 15) who were going through an open
      heart surgery had 500 mg l(-1) of Ptx added to their prime solution, whereas the
      patients in the control group (n = 10) only received prime solution. Pre-pump and
      post-pump blood samples were obtained from both groups and assayed for
      interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha
      (TNFalpha). Lung tissue samples that were obtained after the pump were examined
      with light microscopy and stained for tissueTNFalpha. Non-parametric Wilcoxon
      test was utilized for statistical evaluation. In the post-pump period, the
      difference in the IL-6, IL-8 and TNFalpha levels of the two groups was found to
      be statistically significant (P<0.005). The tissue samples from the control group
      had significant staining with TNFalpha. We think that Ptx has important
      protective effects on the lungs during cardiopulmonary bypass.

PMID- 12000009
TI  - Bronchiolitis obliterans organizing pneumonia in cancer: a case series.
AB  - Bronchiolitis obliterans with organizing pneumonia (BOOP) is an infrequently
      encountered clinical condition that can mimic a number of other pathologic lung
      processes. The presentation of this treatable condition in cancer patients has
      not been described in any large series. We conducted a retrospective study of
      patients with BOOP at Memorial Sloan-Kettering Cancer Center, NewYork, NY, U.S.A.
      from January 1992 to December 1999. The type and treatment of primary cancer,
      clinical and radiographic features of initial BOOP presentation, and outcome
      following therapy were recorded. Forty-three patients with an underlying
      diagnosis of cancer were found on lung biopsy to have BOOP as an isolated entity.
      BOOP was encountered in patients with a variety of clinical presentations, and
      many types of malignancies. The symptom patterns were non-specific, as were the
      physiological abnormalities. The only clear relationship between the underlying
      malignancyand the diagnosis of BOOP at presentation was in the chest radiographic
      findings. Patients with solid organ tumors were more likely to have nodular or
      mass like radiographic abnormalities (81%) than to have diffuse infiltrates
      (19%). We observed the opposite pattern in patients with hematologic malignancies
      (22% vs.67%). The vast majority of patients recovered from this condition. In
      conclusion, For cancer patients, BOOP represents a treatable cause of lung
      disease with protean manifestations. BOOP can mimic pulmonary malignancy and
      pulmonary infection. In cancer patients, the evaluation of new pulmonary symptoms
      accompanied by radiographic changes should include a consideration of this
      diagnosis.

PMID- 12000010
TI  - Patients with baseline hypoxemia demonstrate more desaturation during
      bronchoscopy at supine position.

PMID- 12000011
TI  - Re: evaluation of an inspiratory muscle trainer in healthy humans (Respir Med 95:
      526-531): critique of Hart et al.

PMID- 12000012
TI  - The compelling anomaly of chemical intolerance.
AB  - In science, anomalies expose the limitations of existing paradigms and drive the
      search for new ones. In the late 1800s, physicians observed that certain
      illnesses spread from sick, feverish individuals to those contacting them, paving
      the way for the germ theory of disease. The germ theory served as a crude, but
      elegant formulation that explained dozens of seemingly unrelated illnesses
      affecting literally every organ system. Today, we are witnessing another medical
      anomaly-a unique pattern of illness involving chemically exposed groups in more
      than a dozen countries, who subsequently report multisystem symptoms and new
      onset chemical, food, and drug intolerances. These intolerances may be the
      hallmark for a new disease process or paradigm, just as fever is a hallmark for
      infection. The fact that diverse demographic groups, sharing little in common
      except some initial chemical exposure event, develop these intolerances is a
      compelling anomaly pointing to a possible new theory of disease, one that has
      been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the
      potential to explain certain cases of asthma, migraine headaches, and depression,
      as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to
      evolve in two stages: (1) initiation, characterized by a profound breakdown in
      prior, natural tolerance resulting from either acute or chronic exposure to
      chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2)
      triggering of symptoms by small quantities of previously tolerated chemicals
      (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations
      (alcohol, caffeine). While the underlying dynamic remains an enigma, observations
      indicating that affected individuals respond to structurally unrelated drugs and
      experience cravings and withdrawal-like symptoms, paralleling drug addiction,
      suggest that multiple neurotransmitter pathways may be involved.

PMID- 12000013
TI  - Episodic exposures to chemicals: what relevance to chemical intolerance?
AB  - Episodic exposures refer to intermittent acute exposures to chemicals that
      ordinarily have a rapid onset and short duration of effect. There has been a long
      tradition in preclinical behavioral pharmacology of using episodic-exposure
      paradigms in order to establish dose-response functions in individual organisms.
      In these experiments, stable baselines of behavior are first established and then
      followed by administering varying doses of a drug intermittently, for example,
      once or twice a week. The power of this approach is well established; the within
      subjects design reduces error variance, allows exploration of the entire range of
      effective doses, and can be used to identify individual differences in drug
      sensitivity. Of course, the approach is only applicable to reversibly acting
      compounds, and checks need to be included to insure effects of one dose are not
      influenced by prior exposure to another dose. We have used baseline approaches to
      evaluate the effects of pesticides and solvents on the behavior of adult male
      rats and mice. Moreover, a novel probabilistic dose-tolerance analysis applied to
      the data suggests substantial individual differences in chemical sensitivity,
      often spanning orders of magnitude. These results suggest that individual
      differences in chemical sensitivity may be much greater than previously
      acknowledged.

PMID- 12000014
TI  - Environmental risks and public health.
AB  - There are currently a number of initiatives aimed at considering and redefining
      the role of environmental health. These include an effort under the auspices of
      the Institute of Medicine Roundtable on Environmental Health and another under
      the auspices of the American Schools of Public Health. Both will result in
      conferences to be held in the same month of the New York Academy of Sciences
      (NYAS) conference on "The Role of Neural Plasticity in Chemical Intolerance", for
      which this paper is being prepared. This questioning of our definition and of our
      approach to the field of environmental health is an instructive background on
      which to consider the issue of environmental risks and public health-the topic
      given to me by the organizers of the NYAS conference. My approach will be to
      touch on those issues related to the nervous system and to unexplained symptoms
      in keeping with the subject of the conference, as well as to discuss some of the
      broader issues surrounding environmental health.

PMID- 12000015
TI  - Sensitization, subjective health complaints, and sustained arousal.
AB  - The purpose of this presentation is to discuss the possibility that sensitization
      is a psychobiological mechanism underlying not only multiple chemical sensitivity
      (MCS), but a much more general cluster of illness, referred to as "subjective
      health complaints". Sustained arousal, or sustained "stress" responses, may be an
      important factor for the development of these conditions. Patients with
      subjective complaints without objective changes are sometimes referred to as
      having "fashionable diagnoses" or "unexplained symptoms". They may be given
      diagnoses like MCS, epidemic fatigue, chronic fatigue syndrome, burnout, stress,
      a variety of intoxications, environmental illness, radiation, multiple chemical
      hypersensitivity, food intolerance, functional dyspepsia, irritable bowel,
      myalgic encephalitis, postviral syndrome, yuppie flu, fibromyalgia, or vital
      exhaustion. One issue is whether this is one general condition or separate
      entities. Another issue is whether sensitization may be the psychobiological
      mechanism for most or all of these conditions. Finally, is it likely that
      sustained arousal may facilitate the development of sensitization in some or many
      neural circuits? In this review, the main emphasis will be on musculoskeletal
      pain. This is the most frequent and most expensive condition for sickness
      compensation and disability. The comorbidity of other complaints, however, will
      also be taken into account.

PMID- 12000016
TI  - Representation of acute and persistent pain in the human CNS: potential
      implications for chemical intolerance.
AB  - The study of pain may be relevant to the study of chemical intolerance (CI) in
      many ways. Pain is often reported as a symptom of CI and it is defined as a
      subjective experience similar to many other symptoms of CI, making its
      objectification difficult. Furthermore, the CNS plastic changes that underlie the
      development of persistent pain states and abnormal pain responses may share some
      similarities with those involved in the sensitization to environmental chemicals.
      Functional brain imaging studies in humans demonstrate that acute pain evoked by
      nociceptive stimulation is accompanied by the activation of a widely distributed
      network of cerebral structures, including the thalamus and the somatosensory,
      insular, and anterior cingulate cortices. Abnormal activity within these regions
      has been associated with the experience of pain following damage to the
      peripheral or central nervous system (neuropathic pain) in a number of clinical
      populations. In normal individuals, activity within this network is correlated
      with subjective pain perception, is highly modifiable by cognitive interventions
      such as hypnosis and attention, and has been associated with emotions. Other
      cognitive mediators such as expectations can also produce robust changes in pain
      perception (e.g., in placebo analgesia). These effects likely depend on both
      higher-order cerebral structures and descending mechanisms modulating spinal
      nociceptive activity. These psychological processes can be solicited to reduce
      clinical pain and we speculate that they may further attenuate or promote central
      mechanisms involved in the transition from acute to persistent pain states. The
      investigation of central determinants of subjective experience is essential to
      assess the possibility that higher-order brain/psychological processes modulate
      and/or mediate the development of persistent pain states. These factors may
      contribute to the development of symptoms in CI.

PMID- 12000017
TI  - Role of neurotransmitters in sensitization of pain responses.
AB  - Injection of capsaicin into the skin results in pain, primary heat and mechanical
      hyperalgesia, and secondary mechanical allodynia and hyperalgesia. Sensory
      receptors in the area of secondary mechanical allodynia and hyperalgesia are
      unaffected, and so the sensory changes must be due to central actions of the
      initial intense nociceptive discharge that follows the capsaicin injection.
      Central sensitization of the responses of spinothalamic tract neurons lasts
      several hours, but can be prevented by spinal cord administration of non-NMDA and
      NMDA glutamate receptor antagonists or NK1 substance P receptor antagonists. The
      long-lasting increase in excitability of spinothalamic tract cells depends on the
      activation of several second messenger cascades (PKC, PKA, and NO/PKG signal
      transduction pathways). The excitability change also depends on activation of
      calcium/calmodulin-dependent kinase II, which is consistent with the proposal
      that this central sensitization response is a form of long-term potentiation.

PMID- 12000018
TI  - Central neuroplasticity and pathological pain.
AB  - The traditional specificity theory of pain perception holds that pain involves a
      direct transmission system from somatic receptors to the brain. The amount of
      pain perceived, moreover, is assumed to be directly proportional to the extent of
      injury. Recent research, however, indicates far more complex mechanisms. Clinical
      and experimental evidence shows that noxious stimuli may sensitize central neural
      structures involved in pain perception. Salient clinical examples of these
      effects include amputees with pains in a phantom limb that are similar or
      identical to those felt in the limb before it was amputated, and patients after
      surgery who have benefited from preemptive analgesia which blocks the surgery
      induced afferent barrage and/or its central consequences. Experimental evidence
      of these changes is illustrated by the development of sensitization, wind-up, or
      expansion of receptive fields of CNS neurons, as well as by the enhancement of
      flexion reflexes and the persistence of pain or hyperalgesia after inputs from
      injured tissues are blocked. It is clear from the material presented that the
      perception of pain does not simply involve a moment-to-moment analysis of
      afferent noxious input, but rather involves a dynamic process that is influenced
      by the effects of past experiences. Sensory stimuli act on neural systems that
      have been modified by past inputs, and the behavioral output is significantly
      influenced by the "memory" of these prior events. An increased understanding of
      the central changes induced by peripheral injury or noxious stimulation should
      lead to new and improved clinical treatment for the relief and prevention of
      pathological pain.

PMID- 12000019
TI  - Spinal cord neuroplasticity following repeated opioid exposure and its relation
      to pathological pain.
AB  - Convincing evidence has accumulated that indicates neuroplastic changes within
      the spinal cord in response to repeated exposure to opioids. Such neuroplastic
      changes occur at both cellular and intracellular levels. It has been generally
      acknowledged that the activation of N-methyl-D-aspartate (NMDA) receptors plays a
      pivotal role in the development of neuroplastic changes following repeated opioid
      exposure. Intracellular cascades can also be activated subsequent to NMDA
      receptor activation. In particular, protein kinase C has been shown to be a key
      intracellular element that contributes to the behavioral manifestation of
      neuroplastic changes. Moreover, interactions between NMDA and opioid receptors
      can lead to potentially irreversible degenerative neuronal changes in the spinal
      cord in association with the development of opioid tolerance. Interestingly,
      similar cellular and intracellular changes occur in the spinal cord following
      peripheral nerve injury. These findings indicate that interactions exist in the
      spinal cord neural structures between two seemingly unrelated conditions-chronic
      opioid exposure and a pathological pain state. These observations may help
      understand mechanisms of chemical intolerance and multiple chemical sensitivity
      as well as have significant clinical implications in pain management with opioid
      analgesics.

PMID- 12000020
TI  - Cytokines and chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as
      demonstrated by increased numbers of activated T lymphocytes, including cytotoxic
      T cells, as well as elevated levels of circulating cytokines. Nevertheless,
      immune cell function of CFS patients is poor, with low natural killer cell
      cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and
      frequent immunoglobulin deficiencies, most often IgG1 and IgG3. Immune
      dysfunction in CFS, with predominance of so-called T-helper type 2 and
      proinflammatory cytokines, can be episodic and associated with either cause or
      effect of the physiological and psychological function derangement and/or
      activation of latent viruses or other pathogens. The interplay of these factors
      can account for the perpetuation of disease with remission/exacerbation cycles. A
      T-helper type 2 predominance has been seen among Gulf War syndrome patients and
      this feature may also be present in other related disorders, such as multiple
      chemical sensitivity. Therapeutic intervention aimed at induction of a more
      favorable cytokine expression pattern and immune status appears promising.

PMID- 12000021
TI  - Mediators of inflammation and their interaction with sleep: relevance for chronic
      fatigue syndrome and related conditions.
AB  - In humans, activation of the primary host defense system leads to increased or
      decreased NREM sleep quality, depending on the degree of early immune activation.
      Modest elevations of certain inflammatory cytokines are found during experimental
      sleep loss in humans and, in addition, relatively small elevations of cytokines
      are seen following commencement of pharmacological treatments with clozapine, a
      CNS active antipsychotic agent, known to have immunomodulatory properties.
      Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the
      periphery and the CNS, comprise a link between peripheral immune stimulation and
      CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue.
      The debilitating fatigue experienced in chronic fatigue syndrome and related
      diseases may also be related to altered cytokine profiles.

PMID- 12000022
TI  - The role of cytokines in physiological sleep regulation.
AB  - Several growth factors (GFs) are implicated in sleep regulation. It is posited
      that these GFs are produced in response to neural activity and affect input
      output relationships within the neural circuits where they are produced, thereby
      inducing a local state shift. These GFs also influence synaptic efficacy. All the
      GFs currently identified as sleep regulatory substances are also implicated in
      synaptic plasticity. Among these substances, the most extensively studied for
      their role in sleep regulation are interleukin-1beta (IL-1) and tumor necrosis
      factor alpha (TNF). Injection of IL-1 or TNF enhances non-rapid eye movement
      sleep (NREMS). Inhibition of either IL-1 or TNF inhibits spontaneous sleep and
      the sleep rebound that occurs after sleep deprivation. Stimulation of the
      endogenous production of IL-1 and TNF enhances NREMS. Brain levels of IL-1 and
      TNF correlate with sleep propensity; for example, after sleep deprivation, their
      levels increase. IL-1 and TNF are part of a complex biochemical cascade
      regulating sleep. Downstream events include nitric oxide, growth hormone
      releasing hormone, nerve growth factor, nuclear factor kappa B, and possibly
      adenosine and prostaglandins. Endogenous substances moderating the effects of IL
      1 and TNF include anti-inflammatory cytokines such as IL-4, IL-10, and IL-13.
      Clinical conditions altering IL-1 or TNF activity are associated with changes in
      sleep, for example, infectious disease and sleep apnea. As our knowledge of the
      biochemical regulation of sleep progresses, our understanding of sleep function
      and of many clinical conditions will improve.

PMID- 12000023
TI  - Cytokine-induced sickness behavior: mechanisms and implications.
AB  - Sickness behavior refers to a coordinated set of behavioral changes that develop
      in sick individuals during the course of an infection. At the molecular level,
      these changes are due to the brain effects of proinflammatory cytokines such as
      interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha). Peripherally
      released cytokines act on the brain via a fast transmission pathway involving
      primary afferent nerves innervating the bodily site of inflammation and a slow
      transmission pathway involving cytokines originating from the choroid plexus and
      circumventricular organs and diffusing into the brain parenchyma by volume
      transmission. At the behavioral level, sickness behavior appears to be the
      expression of a central motivational state that reorganizes the organism
      priorities to cope with infectious pathogens. There is evidence that the sickness
      motivational state can interact with other motivational states and respond to
      nonimmune stimuli probably by way of sensitization and/or classical conditioning.
      However, the mechanisms that are involved in plasticity of the sickness
      motivational state are not yet understood.

PMID- 12000024
TI  - Potential mechanisms in chemical intolerance and related conditions.
AB  - The symptom of chemical intolerance may occur in isolation, but often occurs in
      conjunction with other chronic symptoms such as pain, fatigue, memory
      disturbances, etc. This frequent clustering of symptoms in individuals has led to
      the definition of several chronic multisymptom syndromes, such as multiple
      chemical sensitivity, fibromyalgia, chronic fatigue syndrome, and Gulf War
      illnesses. The aggregate research into these syndromes has suggested some
      unifying mechanisms that contribute to symptomatology. Multiple lines of evidence
      suggest that there is aberrant function of numerous efferent neural pathways,
      such as the autonomic nervous system and hypothalamic-pituitary axes, in subsets
      of individuals with these conditions. There is perhaps the greatest evidence for
      abnormal sensory processing in these syndromes, with a low "unpleasantness
      threshold" for multiple types of sensory stimuli. Psychological and behavioral
      factors are known to play a significant role in initiating or perpetuating
      symptoms in some persons with these illnesses. In the field of pain research, the
      interrelationship between physiologic and psychologic factors in symptom
      expression has been well studied. Using both established and novel methodologies,
      studies have suggested that psychologic factors such as hypervigilance and
      expectancy are playing a relatively minor role in most individuals with
      fibromyalgia and that clear evidence exists of physiologic amplification of
      sensory stimuli. These studies need to be extended to more sensory tasks and to
      larger numbers of subjects with related conditions. It is of note, though, that
      existing data on this spectrum of illnesses would suggest that there may be
      greater psychologic contributions to symptomatology if an illness is defined in
      part by behavior (e.g., avoidance of chemical exposures) rather than on the basis
      of symptoms alone.

PMID- 12000025
TI  - Controlled exposures to volatile organic compounds in sensitive groups.
AB  - Sensitivities to chemicals are characterized by symptoms in multiple organ
      systems in response to low-level chemical exposures. This paper reviews studies
      of controlled exposures to odorants and to mixtures of volatile organic
      compounds. Sensitive subgroups include subjects who met Cullen's 1987 criteria
      for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue
      syndrome and chemical sensitivity (CFS/CS), and subjects with specific self
      reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE
      sensitive). All studies include comparison of age- and sex-matched healthy
      controls. Studies of olfaction did not support unusual sensitivity, defined as
      lower odor thresholds, among MCS subjects; however, a dose-response pattern of
      symptoms was observed in response to suprathreshold concentrations of phenyl
      ethyl alcohol. In blinded, controlled exposures to clean air, gasoline,
      gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with
      MTBE-sensitive subjects reporting significantly increased symptoms to
      gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end
      tidal CO2) in response to odor of chemical mixtures may mediate symptoms for
      subjects with generalized chemical sensitivities, but not for those whose
      sensitivities are confined to specific chemicals. For example, Gulf War veterans
      with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while
      exposure to MTBE did not produce any psychophysiologic changes in MTBE-sensitive
      subjects. Controlled olfactory and exposure studies reveal that significant
      responses can be observed in chemically sensitive subjects even when de
      adaptation has not occurred. However, these studies suggest that symptoms are not
      necessarily accompanied by changes in physiologic arousal. Subject
      characteristics play a critical role in outcomes.

PMID- 12000026
TI  - Role of gaseous neurotransmitters in the hypothalamic-pituitary-adrenal axis.
AB  - Nitric oxide (NO) is an unstable gas that plays important roles in the brain in
      general and in neuroendocrine functions in particular. We have shown that NO
      exerts opposite effects within the median eminence-pituitary axis, where it
      inhibits ACTH responses to blood-borne signals [such as the systemic injection of
      proinflammatory cytokines or vasopressin (VP)], and structures protected by the
      blood-brain barrier, where it stimulates the synthesis of the hypothalamic
      peptides, corticotropin-releasing factor (CRF) and VP. As a result, when an
      animal is exposed to stimuli that acutely activate the paraventricular nucleus of
      the hypothalamus as well as the release of peptides from nerve terminals (such as
      mild inescapable foot shocks), the net influence of NO on the ACTH response will
      represent the balance between these two effects. Based on experiments conducted
      with rats, we propose that, in shocks of low intensity, ACTH release primarily
      depends, at least in the initial phase, on the interaction between NO and VP (and
      consequently is augmented by reagents that block NO formation); in shocks of
      higher intensity, the interaction between NO and the hypothalamus predominates
      (i.e., it is inhibited by reagents that block NO formation).

PMID- 12000027
TI  - Plasticity of the hippocampus: adaptation to chronic stress and allostatic load.
AB  - The hippocampus is an important structure for declarative, spatial, and
      contextual memory and is implicated in the perception of chronic pain. The
      hippocampal formation is vulnerable to damage from seizures, ischemia, and head
      trauma and is particularly sensitive to the effects of adrenal glucocorticoids
      secreted during the diurnal rhythm and chronic stress. Adrenal steroids typically
      have adaptive effects in the short run, but promote pathophysiology when there is
      either repeated stress or dysregulation of the HPA axis. The damaging actions of
      glucocorticoids under such conditions have been termed "allostatic load",
      referring to the cost to the body of adaptation to adverse conditions. Adrenal
      steroids display both protective and damaging effects in the hippocampus. They
      biphasically modulate excitability of hippocampal neurons, and high
      glucocorticoid levels and severe acute stress impair declarative memory in a
      reversible manner. The hippocampus also displays structural plasticity, involving
      ongoing neurogenesis of the dentate gyrus, synaptogenesis under control of
      estrogens in the CA1 region, and dendritic remodeling caused by repeated stress
      or elevated levels of exogenous glucocorticoids in the CA3 region. In all three
      forms of structural plasticity, excitatory amino acids participate along with
      circulating steroid hormones. Glucocorticoids and stressors suppress neurogenesis
      in the dentate gyrus. They also potentiate the damage produced by ischemia and
      seizures. Moreover, the aging rat hippocampus displays elevated and prolonged
      levels of excitatory amino acids released during acute stress. Our working
      hypothesis is that structural plasticity in response to repeated stress starts
      out as an adaptive and protective response, but ends up as damage if the
      imbalance in the regulation of the key mediators is not resolved. It is likely
      that morphological rearrangements in the hippocampus brought on by various types
      of allostatic load alter the manner in which the hippocampus participates in
      memory functions and it is conceivable that these may also have a role in chronic
      pain perception.

PMID- 12000028
TI  - Acquiring symptoms in response to odors: a learning perspective on multiple
      chemical sensitivity.
AB  - In this chapter, a learning account is discussed as a potential explanation for
      the symptoms in multiple chemical sensitivity. Clinical evidence is scarce and
      anecdotal. A laboratory model provides more convincing results. After a few
      breathing trials containing CO2-enriched air as an unconditioned stimulus in a
      compound with harmless odor substances as conditioned stimuli, subjective
      symptoms are elicited and respiratory behavior is altered by the odors only.
      Also, mental images can become conditioned stimuli to trigger subjective
      symptoms. The learning effects cannot be explained by a response bias or by
      conditioned arousal, and they appear to involve basic associative processes that
      do not overlap with aware cognition of the relationship between the odors and the
      CO2 inhalation. Learned symptoms generalize to new odors and they can be
      eliminated in a Pavlovian extinction procedure. In accordance with clinical
      findings, neurotic subjects and psychiatric cases are more vulnerable to learning
      subjective symptoms in response to odors. Consistent with a learning account,
      cognitive-behavioral treatment techniques appear to produce beneficial results in
      clinical cases. Several criticisms and unresolved questions regarding the
      potential role of learning mechanisms are discussed.

PMID- 12000029
TI  - Pavlovian conditioning of emotional responses to olfactory and contextual
      stimuli: a potential model for the development and expression of chemical
      intolerance.
AB  - Chemical intolerance (CI) in humans is a poorly understood phenomenon of
      uncertain etiology, seemingly influenced by multiple factors both within and
      between affected individuals. Several authors have suggested that the development
      of CI in some individuals may be due, at least in part, to Pavlovian conditioning
      processes in which the expression of overt symptoms to certain substances
      reflects classically conditioned responses to previously neutral olfactory and
      contextual stimuli. In this paper, we describe the potential relationship between
      olfactory and contextual conditioning in experimental animals and the development
      and expression of CI in humans. Furthermore, as significant advances have been
      made in delineating the brain areas that underlie these learned responses, we
      also review recent research on the contributions of the amygdala and perirhinal
      cortical region to olfactory and contextual fear conditioning.

PMID- 12000030
TI  - Central nervous system effects from a peripherally acting cholinesterase
      inhibiting agent: interaction with stress or genetics.

PMID- 12000031
TI  - Symptom learning in response to odors in a single odor respiratory learning
      paradigm.

PMID- 12000032
TI  - Deep subcortical (including limbic) hypermetabolism in patients with chemical
      intolerance: human PET studies.

PMID- 12000033
TI  - Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple
      chemical sensitivity, chronic fatigue syndrome, and posttraumatic stress
      disorder.
AB  - Various types of evidence implicate nitric oxide and an oxidant, possibly
      peroxynitrite, in MCS and chemical intolerance (CI). The positive feedback loops
      proposed earlier for CFS may explain the chronic nature of MCS (CI) as well as
      several of its other reported properties. These observations raise the
      possibility that this proposed elevated nitric oxide/peroxynitrite mechanism may
      be the mechanism of a new disease paradigm, answering the question raised by
      Miller earlier: "Are we on the threshold of a new theory of disease?"

PMID- 12000034
TI  - Sensitization studies in chemically intolerant individuals: implications for
      individual difference research.
AB  - Chemical intolerance (CI) is an individual difference trait in which persons
      report feeling ill in multiple physiological systems from low levels of a wide
      range of chemically unrelated environmental substances. This paper discusses the
      neural sensitization model for progressive host amplification of polysymptomatic
      responses elicited by chemical exposures following an initiating event. The
      sensitization model accommodates hypotheses for initiating and eliciting CI in
      human populations that involve both environmental chemicals and physical or
      psychological stressors. Recent studies in this laboratory have demonstrated
      sensitization in individuals with CI over repeated sessions for dependent
      variables such as electroencephalographic (EEG) activity and diastolic blood
      pressure. Psychological distress variables alone do not explain these findings.
      Individuals with CI and/or vulnerability to sensitization share specific
      characteristics, for example, female gender, certain genetic background
      (offspring of alcohol-preferring parents), and personal preference for high
      sugar/ carbohydrate intake. Overall, the data suggest that the 15-30% of the
      general population who report heightened CI are highly sensitizable.
      Sensitizability may serve an adaptive, sentinel function in threatening
      environments with poor signal-to-noise ratios. However, as sensitization
      gradually shifts operating set points of physiological systems out of the normal
      range in response to allostatic load, this process may contribute to the
      development of chronic, polysymptomatic health conditions such as multiple
      chemical sensitivity and/or fibromyalgia. Individual response specificity and
      stereotypy rather than toxicant properties may determine which types of central,
      autonomic, and/or peripheral nervous system dysfunctions manifest at subclinical
      and clinical levels.

PMID- 12000035
TI  - The Iowa follow-up of chemically sensitive persons.
AB  - Clinical symptoms and self-reported health status in persons reporting multiple
      chemical sensitivities (MCS) are presented from a 9-year follow-up study.
      Eighteen (69%) subjects from a sample of 26 persons originally interviewed in
      1988 were followed up in 1997 and given structured interviews and self-report
      questionnaires. In terms of psychiatric diagnosis, 15 (83%) met DSM-IV criteria
      for a lifetime mood disorder, 10 (56%) for a lifetime anxiety disorder, and 10
      (56%) for a lifetime somatoform disorder. Seven (39%) of subjects met criteria
      for a personality disorder using the Personality Diagnostic Questionnaire-IV.
      Self-report data from the Illness Behavior Questionnaire and Symptom Checklist-90
      Revised show little change from 1988. The 10 most frequent complaints attributed
      to MCS were headache, memory loss, forgetfulness, sore throat, joint aches,
      trouble thinking, shortness of breath, back pain, muscle aches, and nausea.
      Global assessment showed that 2 (11%) had "remitted", 8 (45%) were "much" or
      "very much" improved, 6 (33%) were "improved", and 2 (11%) were
      "unchanged/worse". Mean scores on the SF-36 health survey showed that, compared
      to U.S. population means, subjects reported worse physical functioning, more
      bodily pain, worse general health, worse social functioning, and more emotional
      role impairment; self-reported mental health was better than the U.S. population
      mean. All subjects maintained a belief that they had MCS; 16 (89%) acknowledged
      that the diagnosis was controversial. It is concluded that the subjects remain
      strongly committed to their diagnosis of MCS. Most have improved since their
      original interview, but many remain symptomatic and continue to report ongoing
      lifestyle changes.

PMID- 12000036
TI  - Repeated formaldehyde effects in an animal model for multiple chemical
      sensitivity.
AB  - Chemical intolerance is a phenomenon observed in multiple chemical sensitivity
      (MCS) syndrome, an ill-defined disorder in humans attributed to exposure to
      volatile organic compounds. Amplification of symptoms in individuals with MCS
      resembles the phenomenon of psychostimulant- and stress-induced sensitization in
      rodents. We have recently tested in rats the hypothesis that repeated chemical
      exposure produces sensitization of central nervous system (CNS) circuitry. A rat
      model of MCS in our laboratory has employed several endpoints of CNS function
      after repeated formaldehyde (Form) exposure (1 h/day x 5 days/week x 4 weeks).
      Repeated Form exposure produced behavioral sensitization to later cocaine
      injection, suggesting altered dopaminergic sensitivity in mesolimbic pathways.
      Rats given repeated Form also demonstrated increased fear conditioning to odor
      paired with footshock, implicating amplification of neural circuitry guiding fear
      responding to a conditioned odor cue. Recent studies examining the effects of
      repeated Form on locomotor activity during each daily exposure showed a decrease
      in rearing activity after 12-15 days of Form exposure compared to air-exposed
      controls. EEG recordings taken 1 week after withdrawal from daily Form revealed
      altered sleep architecture. Some of the differences in sleep disappeared after
      subsequent brief (15 min) challenge with Form the next day. Overall, the findings
      indicate that repeated low-level chemical exposure produces behavioral changes
      that may be akin to those observed in individuals with MCS, such as greater
      sensitivity to chemicals manifest as increased anxiety upon chemical exposure and
      altered sleep and/or fatigue. Study of the underlying CNS changes will provide a
      basis for mechanistically based animal models for MCS.

PMID- 12000037
TI  - Does the kindling model of epilepsy contribute to our understanding of multiple
      chemical sensitivity?
AB  - Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report an
      increased sensitivity to low levels of chemicals in the environment. Kindling is
      a model of synaptic plasticity whereby repeated low-level electrical stimulation
      to a number of brain sites leads to permanent increases in seizure
      susceptibility. Stimulation that is initially subthreshold for subclinical
      seizure provocation comes, over time, to elicit full-blown motor seizures.
      Kindling can also be induced by chemical stimulation, and repeated exposures to
      some pesticides have been shown to induce signs of behavioral seizure, facilitate
      subsequent electrical kindling, and induce subclinical electrographic signs of
      hyperexcitability in the amygdala. Many of the symptoms of MCS suggest that CNS
      limbic pathways involved in anxiety are altered in individuals reporting MCS.
      Limbic structures are among the most susceptible to kindling-induced seizures,
      and persistent cognitive and emotional sequelae have been associated with
      temporal lobe epilepsy (TLE) in humans and kindling in animals. Thus, a number of
      parallels exist between kindling and MCS phenomena, leading to initial
      speculations that MCS may occur via a kindling-like mechanism. However, kindling
      requires the activation of electrographic seizure discharge and has thus been
      primarily examined as a model for TLE. Events leading to the initial evocation of
      a subclinical electrographic seizure have been much less well studied. It is
      perhaps these events that may serve as a more appropriate model for the enhanced
      chemical responsiveness characteristic of MCS. Alternatively, kindling may be
      useful as a tool to selectively increase sensitivity in subcomponents of the
      neural fear circuit to address questions relating the role of anxiety in the
      development and expression of MCS.

PMID- 12000038
TI  - A genetic rat model of cholinergic hypersensitivity: implications for chemical
      intolerance, chronic fatigue, and asthma.
AB  - The fact that only some individuals exposed to environmental chemicals develop
      chemical intolerance raises the possibility that genetic factors could be
      contributing factors. The present communication summarizes evidence from a
      genetic animal model of cholinergic supersensitivity that suggests that an
      abnormal cholinergic system could be one predisposing genetic factor. The
      Flinders Sensitive Line (FSL) rats were established by selective breeding for
      increased responses to an organophosphate. It was subsequently found that these
      FSL rats were also more sensitive to direct-acting muscarinic agonists and had
      elevated muscarinic receptors compared to the selectively bred parallel group,
      the Flinders Resistant Line (FRL) rats, or randomly bred control rats. Increased
      sensitivity to cholinergic agents has also been observed in several human
      populations, including individuals suffering from chemical intolerance. Indeed,
      the FSL rats exhibit certain behavioral characteristics such as abnormal sleep,
      activity, and appetite that are similar to those reported in these human
      populations. In addition, the FSL rats have been reported to exhibit increased
      sensitivity to a variety of other chemical agents. Peripheral tissues, such as
      intestinal and airway smooth muscle, appear to be more sensitive to both
      cholinergic agonists and an antigen, ovalbumin. Hypothermia, a centrally mediated
      response, is more pronounced in the FSL rats after nicotine and alcohol, as well
      as agents that are selective for the dopaminergic and serotonergic systems. In
      some cases, the increased sensitivity has been detected in the absence of any
      changes in the receptors with which the drugs interact (dopamine receptors),
      while receptor changes have been seen in other cases (nicotine receptors).
      Therefore, there may be multiple mechanisms underlying the multiple chemical
      sensitivity-chemical intolerance of the FSL rats. An elucidation of these
      mechanisms may provide useful clues to those involved in chemical intolerance in
      humans.

PMID- 12000039
TI  - Short- and medium-term outcome differences in women and men after primary
      percutaneous transluminal mechanical revascularization for acute myocardial
      infarction.
AB  - Women presenting with acute myocardial infarction (AMI) have a higher mortality
      with conventional medical and thrombolytic therapy when compared with men. The
      outcome after primary percutaneous transluminal mechanical revascularization has
      not yet been fully investigated. This study was performed to compare the
      characteristics and the short- and medium-term outcomes of women and men with AMI
      treated with primary percutaneous revascularization. A total of 182 consecutive
      patients (62 women and 120 men) were included. Baseline clinical characteristics
      were similar except that women were older than men, presented more often in
      cardiogenic shock, and had smaller reference vessel diameters. Stents and
      abciximab were used equally, but abciximab was stopped more often in women before
      completion of the 12-hour infusion because of higher bleeding rates. Acute
      procedural success rates were similar (92% and 97%) but mortality was much higher
      in women, both at 30-day follow-up (100% vs 0.9%; p <0.05) and during a mean
      follow-up of 6.9 +/- 4.1 months (15% vs 4.4%; p <0.05). Women also experienced
      more unfavorable cardiovascular events (recurrent unstable angina or AMI, target
      vessel revascularization) than men. However, after control for baseline clinical
      differences in a multivariate analysis, gender was not an independent predictor
      of survival, whereas age, cardiogenic shock, and completion of a 12-hour
      abciximab infusion were.

PMID- 12000040
TI  - Comparison of electrocardiographic-gated technetium-99m sestamibi single-photon
      emission computed tomographic imaging and rest-redistribution thallium-201 in the
      prediction of myocardial viability.
AB  - Although the combined assessment of perfusion and function using rest
      electrocardiographic (ECG)-gated technetium-99m (Tc-99m) sestamibi single-photon
      emission computed tomographic (SPECT) imaging has been shown to improve
      sensitivity and accuracy over perfusion alone in the prediction of myocardial
      viability, no data are available comparing this technique with rest
      redistribution thallium-201. Thirty patients with coronary artery disease and
      left ventricular dysfunction (ejection fraction < or = 40%) underwent rest
      redistribution thallium-201 and rest ECG-gated Tc-99m sestamibi SPECT imaging
      before revascularization and rest ECG-gated Tc-99m sestamibi SPECT imaging at 1
      or 6 weeks after revascularization. All thallium-201 and Tc-99m sestamibi images
      were interpreted by a consensus agreement of 3 experienced readers without
      knowledge of patient identity or time of imaging with Tc-99m sestamibi (before or
      after revascularization) using a 17-segment model. Concordance between techniques
      for the prediction of viability was 89% (kappa 0.556 +/- 0.109). With rest
      redistribution thallium-201, sensitivity, specificity, positive predictive value,
      negative predictive value, and predictive accuracy were 95%, 59%, 88%, 78%, and
      86%, respectively. With rest ECG-gated Tc-99m sestamibi SPECT imaging,
      sensitivity, specificity, positive predictive value, negative predictive value,
      and predictive accuracy were 96%, 55%, 87%, 80%, and 86%, respectively (p = NS vs
      rest-redistribution thallium-201). Although both techniques are comparable for
      detecting viable myocardium, rest ECG-gated Tc-99m sestamibi SPECT imaging allows
      direct assessment of both myocardial perfusion and ventricular function, which
      may be clinically useful in patients who require assessment of myocardial
      viability.

PMID- 12000041
TI  - A comparison of ionic versus nonionic contrast medium during primary percutaneous
      transluminal coronary angioplasty for acute myocardial infarction (GUSTO IIb).
      Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary
      Syndromes.
AB  - The clinical impact of contrast medium selection during primary percutaneous
      transluminal coronary angioplasty for acute myocardial infarction (AMI) has not
      been studied. We compared the clinical outcomes of patients who received ionic
      versus nonionic low osmolar contrast medium in the setting of primary
      percutaneous transluminal coronary angioplasty for AMI in the second Global Use
      of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes
      (GUSTO IIb) trial. Univariable and multivariable analyses were performed to
      assess the relation between contrast medium selection and clinical outcome
      (death, reinfarction, or refractory ischemia) at 30 days. Although baseline
      clinical and angiographic characteristics were generally similar between the 2
      groups, patients who received ionic, low osmolar contrast were less likely to
      have been enrolled at a US site (23% vs 43%, p = 0.001) and less likely to have
      occlusion of the left anterior descending coronary artery (34% vs 47%, p = 0.03)
      or a history of prior AMI (8% vs 16%, p = 0.02). The triple composite end point
      of death, reinfarction, or refractory ischemia occurred less frequently in the
      ionic group, both in the hospital (4.4% vs 11%, p = 0.018) and at 30 days (5.5%
      vs 11%, p = 0.044). Although the trend favoring ionic contrast persisted, the
      differences were no longer statistically significant after adjustment for
      imbalances in baseline characteristics using a risk model developed from the
      study sample (n = 454, adjusted odds ratio for ionic contrast 0.48 [0.22 to
      1.02], p = 0.055), and using a model developed from the entire GUSTO IIb study
      cohort (n = 12,142, adjusted odds ratio for ionic contrast 0.50 [0.23 to 1.06], p
      = 0.072). The results of this observational study warrant further elucidation by
      a randomized study design in this setting.

PMID- 12000042
TI  - Early mobilization after protamine reversal of heparin following implantation of
      phosphorylcholine-coated stents in totally occluded coronary arteries.
AB  - Immediate removal of the femoral artery sheath after coronary angioplasty may
      allow rapid mobilization and reduces the number of in-hospital days. We studied
      the early and 1-month clinical and angiographic follow-up of patients having
      heparin reversed with protamine after implantation of phosphorylcholine-coated
      metal (Divysio) stents, followed by removal of the femoral artery sheath. Fifty
      patients (37 men, mean age 59 +/- 10 years) with stable angina pectoris and a
      single totally occluded artery (1 unprotected left main stem, 15 left anterior
      descending, 11 left circumflex, 23 right) underwent coronary angioplasty.
      Antithrombotic medication was salicylic acid 75 to 160 mg before, heparin bolus
      7,500 IU during, and protamine sulfate 25 mg and oral ticlopidine 250 mg after
      the procedure. Angiography was performed after 30 minutes and at 1 month. The
      mean number of stents was 1.4 +/- 0.6/lesion, with a mean final diameter of 2.69
      +/- 0.40 mm. One stent thrombus was detected after 30 minutes and was treated
      with balloon dilatation. One patient underwent emergency bypass surgery for non
      stent-related problems. Forty-six patients were mobile after 5 hours, and 2 after
      >5 hours. At 1 month there had been no major coronary end points,
      rehospitalizations, groin bleeding, or more thrombi. One episode of transient
      pulmonary edema occurred after protamine injection. Thirty-eight patients (79%)
      had no angina at 1 month, maximal bicycle exercise capacity increased from 128 +/
      42 to 160 +/- 45 W (p <0.05), and left ventricular ejection fraction increased
      from 63% to 68% (p <0.05). Thus, reversal of heparin with protamine sulfate after
      implantation of a phosphorylcholine-coated stent enables early mobilization. This
      approach seems safe in patients with 1 -vessel total occlusions and angioplasty
      could be performed as an outpatient procedure.

PMID- 12000043
TI  - Effects of surgery for postinfarction ventricular tachycardia on parameters of
      left ventricular function.
AB  - Heart failure is the leading cause of death in patients after surgery for
      ventricular tachycardia. This study examines the effects of antiarrhythmic
      surgery on 4 parameters of left ventricular (LV) function. Global ejection
      fraction, segmental wall motion score, homogeneity of contraction, and diastolic
      function were measured in 32 patients by technetium-99m radionuclide
      ventriculography. Ejection fraction was measured from the left anterior oblique
      image. Wall motion score was assessed semiquantitatively for 11 LV segments from
      3 projections. Homogeneity of contraction was expressed as the SD of the LV phase
      analysis curve during systole from the left anterior oblique image. Diastolic
      function was expressed in terms of peak and mean first time derivative of the
      action potential (dV/dt) of the LV function curve. Subgroup analyses were
      performed to distinguish the effects of aneurysmectomy, coronary artery bypass
      grafting, and changes in angiotensin converting enzyme inhibitor therapy. Mean
      systolic function improved after surgery (ejection fraction 22% vs 32%, p <0001;
      wall motion score 20 vs 13, p <0.0001; phase analysis 18 vs 12, p <0.03). Mean
      diastolic function also improved (peak dV/dt 0.83 +/- 0.32 vs 1.49 +/- 0.39, p =
      0.006; mean dV/dt 0.41 +/- 0.15 vs 0.76 +/- 0.27, p = 0.006). Improvements were
      not confined to those who had aneurysmectomy or coronary bypass grafting and were
      not explained by changes in vasodilator therapy. Thus, antiarrhythmic surgery
      does not inherently damage LV function. Significant improvements were observed in
      most patients. Failure to improve indicated a poor longer term prognosis.

PMID- 12000044
TI  - A T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide
      synthase gene and coronary arterial vasomotility.
AB  - In the endothelium, synthesis of nitric oxide (NO) from the amino acid L-arginine
      is catalyzed by the endothelial NO synthase (eNOS), and the continuously
      generated NO serves to maintain basal vascular tone. Recently, we discovered a T
      786-->C mutation in the 5'-flanking region of the eNOS gene; this mutation
      reduced the promoter activity of the eNOS gene and was associated with coronary
      spasm. We examined the vasomotility of the epicardial coronary artery in subjects
      with and without T-736-->C mutation. We examined vasomotility in 32 consecutive
      subjects who were heterozygotes for the T-786-->C mutation and in 68 subjects
      without the T-786-->C mutation who had equivalent age, sex, and smoking status at
      the proximal and distal segments of the left descending coronary artery by
      performing quantitative coronary angiography. In subjects with the mutant allele
      (-786C allele), basal diameters of proximal and distal segments before
      intracoronary injection of acetylcholine (ACh) were less than diameters in
      subjects without the mutant allele (p <0.05), although there was no difference
      between subjects with and without the mutant allele in the diameters of coronary
      arteries after isosorbide dinitrate (ISDN) administration. When we compared the
      changes in diameters, both ACh-induced vasoconstriction and ISDN-induced
      vasodilatation in subjects with the mutant allele were significantly increased in
      the proximal (p <0.01, p <0.001, respectively) and distal segments (p <0.03, p
      <0.01, respectively). Taken together, these findings strongly suggest that the T
      786-->C mutation increases the basal tone of the coronary artery, and enhances
      the response to the constrictor effects of ACh and the dilator effect of ISDN
      because of reducing the endothelial NO synthesis.

PMID- 12000045
TI  - Eosinophil counts and plasma fibrinogen in patients with vasospastic angina
      pectoris.
AB  - Epidemiologic studies have suggested a relation between white blood cell (WBC)
      counts and the incidence of coronary heart disease. However, the relation between
      vasospastic angina pectoris (VAP) and WBC counts remains to be elucidated. To
      clarify the relation between differential and WBC counts in VAP, we compared the
      hematologic values, blood chemical values, plasma fibrinogen levels, C-reactive
      protein levels, and coronary risk factors in patients with spontaneous attacks of
      VAP (n = 39) with those in patients with stable effort angina pectoris (EAP, n =
      35) and in control subjects (n = 19). Patients with VAP were further divided into
      mild VAP (n = 22) and severe VAP groups (n = 17). There were no differences in
      the coronary risk factors, body temperature, total WBC counts, and C-reactive
      protein levels among the control, EAP, mild VAP, and severe VAP groups, except
      that the high-density lipoprotein cholesterol in the EAP group was significantly
      lower than that in the control group (p <0.01). In contrast, the eosinophil
      counts were significantly higher in the severe VAP group than in the other 3
      groups (p <0.01). Plasma fibrinogen levels were also significantly higher in the
      severe VAP group than in the other 3 groups (p <0.05). The follow-up study for
      differential and WBC counts in patients with VAP (n = 23) demonstrated that,
      after medical therapy, the eosinophil counts were significantly decreased to the
      some level as those in the control group (p <0.0001). Thus, the eosinophil counts
      and plasma fibrinogen levels could predict the severity of VAP. Furthermore, a
      follow-up study in patients with VAP suggests that coronary vasospasm could
      result in an increase in eosinophil counts.

PMID- 12000046
TI  - The cardiovascular event reduction tool (CERT)--a simplified cardiac risk
      prediction model developed from the West of Scotland Coronary Prevention Study
      (WOSCOPS).
AB  - The clinical decision to treat hypercholesterolemia is premised on an awareness
      of patient risk, and cardiac risk prediction models offer a practical means of
      determining such risk. However, these models are based on observational cohorts
      where estimates of the treatment benefit are largely inferred. The West of
      Scotland Coronary Prevention Study (WOSCOPS) provides an opportunity to develop a
      risk-benefit prediction model from the actual observed primary event reduction
      seen in the trial. Five-year Cox model risk estimates were derived from all
      WOSCOPS subjects (n = 6,595 men, aged 45 to 64 years old at baseline) using
      factors previously shown to be predictive of definite fatal coronary heart
      disease or nonfatal myocardial infarction. Model risk factors included age,
      diastolic blood pressure, total cholesterol/ high-density lipoprotein ratio
      (TC/HDL), current smoking, diabetes, family history of fatal coronary heart
      disease, nitrate use or angina, and treatment (placebo/ 40-mg pravastatin). All
      risk factors were expressed as categorical variables to facilitate risk
      assessment. Risk estimates were incorporated into a simple, hand-held slide rule
      or risk tool. Risk estimates were identified for 5-year age bands (45 to 65
      years), 4 categories of TC/HDL ratio (<5.5, 5.5 to <6.5, 6.5 to <7.5, > or =
      7.5), 2 levels of diastolic blood pressure (<90, > or = 90 mm Hg), from 0 to 3
      additional risk factors (current smoking, diabetes, family history of premature
      fatal coronary heart disease, nitrate use or angina), and pravastatin treatment.
      Five-year risk estimates ranged from 2% in very low-risk subjects to 61% in the
      very high-risk subjects. Risk reduction due to pravastatin treatment averaged
      31%. Thus, the Cardiovascular Event Reduction Tool (CERT) is a risk prediction
      model derived from the WOSCOPS trial. Its use will help physicians identify
      patients who will benefit from cholesterol reduction.

PMID- 12000047
TI  - Comparison of event rates and survival in patients with unexplained syncope
      without documented ventricular tachyarrhythmias versus patients with documented
      sustained ventricular tachyarrhythmias both treated with implantable cardioverter
      defibrillators.
AB  - Patients with unexplained syncope and inducible ventricular tachyarrhythmias
      during electrophysiologic testing have an increased cardiac mortality rate. We
      compared event rates and survival of 178 patients with unexplained syncope and no
      documented ventricular arrhythmias (syncope group) versus 568 patients with
      documented sustained ventricular tachycardia (VT or fibrillation (VF) (VT/VF
      group) treated, as part of a lead (Ventritex TVL) investigation, with similar
      implantable cardioverter-defibrillators (ICDs) capable of extensive data storage.
      The 2 groups shared similar clinical characteristics. The mean follow-up was 11
      months for the syncope group and 14 months for the VT/VF group. The mean time
      from device implantation to first appropriate therapy was similar in the 2 groups
      (109 +/- 140 vs 93 +/- 131 days, p = 0.40). Actuarial probability of appropriate
      ICD therapy was 49% and 55% at 1 and 2 years, respectively, in syncope group and
      49% and 58% in VT/VF group (p = 0.57). Recurrent syncope was associated with
      ventricular tachyarrhythmias in 85% and 92% of the syncope group and VT/VF group,
      respectively (p = 0.54). At 2 years, actuarial survival was 91% in the syncope
      group and 93% in VT/VF group (p = 0.85). We conclude that patients treated with
      ICD with unexplained syncope and induced VT/VF have an equally high incidence of
      appropriate ICD therapy and low mortality compared with similar patients with
      documented VT/VF. These findings, plus the high association between recurrent
      syncope and ventricular arrhythmias, indicate that VT/VF are likely etiologies in
      selected patients with unexplained syncope and support ICD therapy in such cases.

PMID- 12000048
TI  - Extracardiac anomalies in the heterotaxy syndromes with focus on anomalies of
      midline-associated structures.
AB  - The extracardiac defects in patients with heterotaxy have not been examined as
      extensively as cardiac defects. We found a high incidence of midline-associated
      defects in 160 autopsied cases of heterotaxy (asplenia, polysplenia, or single
      right-sided spleen). Fifty-two percent of patients with left-sided polysplenia
      had a midline-associated defect, as did 45% of those with asplenia. Most common
      were musculoskeletal or genitourinary anomalies, as well as cleft palate. Fused
      adrenal glands and anal stenosis or atresia occurred exclusively among patients
      with asplenia. A midline anomaly was twice as likely to be detected on complete
      autopsy than from clinical findings alone. Linkage studies should take into
      account that affected subjects may have isolated subclinical midline defects. The
      high incidence of midline-associated defects supports the theory that the midline
      plays a critical role in establishing left-right asymmetry in the body.
      Comparison of these defects with mouse models of laterality defects suggests that
      mutations that disrupt the transforming growth factor beta pathway may result in
      heterotaxy.

PMID- 12000049
TI  - Reversal of severe late left ventricular failure after pediatric heart
      transplantation and possible role of plasmapheresis.
AB  - Late acute cardiac graft failure carries a high mortality in adults. Vascular
      mediators and factors other than classic T-cell-mediated rejection may play a
      role in this process, and aggressive multimodality therapy may improve survival.
      We report experience with plasmapheresis in treating late severe acute left
      ventricular dysfunction in a group of pediatric heart transplant recipients. We
      retrospectively reviewed clinical records, echocardiograms, hemodynamics,
      coronary angiograms, biopsy specimens, and treatment regimens for 5 patients with
      7 episodes of late-onset severe graft failure who recovered. Plasmapheresis was
      applied in all cases, in addition to methylprednisolone, cyclophosphamide,
      lympholytic agents, and aggressive supportive care including mechanical
      ventilation and hemofiltration. All patients presented with acute severe left
      ventricular dysfunction 1.4 to 7.9 years (mean 3.6) after orthotopic heart
      transplantation. Mean shortening fraction at presentation was 13 to 23% (mean
      16), initial endomyocardial biopsy specimens were grade 0 to 3B, and
      immunofluorescence studies were negative. Treatment included plasmapheresis,
      cyclophosphamide, mechanical ventilation, hemofiltration, and inotropes. Clinical
      recovery was slow, with 4 to 8 weeks until left ventricular function normalized,
      and 2.2 to 9.4 (mean 4.6) weeks to hospital discharge. At follow-up (50 to 38
      months, mean 24), all are alive. Two patients are well, whereas coronary
      vasculopathy developed in 3. Thus, survival may improve in patients with late
      graft failure with low biopsy score and plasmapheresis combined with
      multimodality therapy.

PMID- 12000050
TI  - Clinical impact of second harmonic imaging and left heart contrast in
      echocardiographic stress testing.
AB  - Second harmonic imaging and left heart contrast agents are recent
      echocardiographic advancements that enhance the assessment of wall motion.
      Because little information exists concerning their clinical impact on
      echocardiographic stress testing in daily practice, this was determined for 9
      month periods before (1997) and after (1998) their introduction. Harmonic imaging
      was used in all patients after its introduction. A second generation intravenous
      left heart contrast agent (Optison) was used at the discretion of the sonographer
      and physician team. Both exercise and dobutamine stress tests were included. At
      the time of study interpretation, diagnostic confidence was assigned as high,
      medium, or low. For all patients who underwent coronary angiography < or = 6
      months after stress testing, the diagnostic accuracy was determined (true
      positive plus true negative/total studies). There were 574 studies before and 746
      studies after implementation. Optison was used in 28% of the harmonic imaging
      studies. Study cancellations due to uninterpretable images fell from 6.4% to 1.2%
      (p <0.001) despite a more obese population completing testing (body mass index:
      29 +/- 7 to 31 +/- 8 kg/m2, p = 0.02), whereas high diagnostic confidence
      increased from 55% to 64% (p <0.001). For the 7% of patients who underwent
      cardiac catheterization, the diagnostic accuracy remained unchanged (74 vs 73%)
      although a prior negative stress test was less common (40% to 20% p = 0.04).
      Thus, these new technologies had a favorable clinical impact.

PMID- 12000051
TI  - Use of echocardiography for predicting myocardial viability in patients with
      reperfused anterior wall myocardial infarction.
AB  - Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography
      (MCE), and ultrasonic tissue characterization with integrated backscatter are
      useful methods for assessing myocardial viability in acute myocardial infarction.
      In this study, we compared the potential of 3 methods for predicting myocardial
      viability in 38 patients with reperfused anterior wall acute myocardial
      infarction. We performed MCE shortly after coronary reperfusion with an
      intracoronary injection of microbubbles. We recorded 2-dimensional integrated
      backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3
      days later. In integrated backscatter images, we placed the region of interest in
      the midwall of the myocardial segment to reconstruct the cyclic variation of
      myocardial integrated backscatter. The myocardial segment was judged viable when
      it showed active contraction 3 months later. Among 74 segments analyzed, 34 were
      judged viable. Presence of contractile response during DSE predicted segmental
      viability with 91% sensitivity and 78% specificity. Intense and homogenous
      contrast enhancement with MCE predicted viability with 82% sensitivity and 73%
      specificity. The presence of synchronous contraction of cyclic variation
      predicted myocardial viability with 79% sensitivity and 83% specificity. There
      were no differences in sensitivity and specificity among the 3 methods. Thus, MCE
      and ultrasonic tissue characterization can predict myocardial viability as
      accurately as DSE in patients with acute myocardial infarction. The logistics of
      the methods may determine clinical application.

PMID- 12000052
TI  - Effect of patient obesity on the accuracy of thallium-201 myocardial perfusion
      imaging.
AB  - The effects of patient habitus (e.g., breast attenuation in women and
      diaphragmatic attenuation in men) have long been recognized as factors that
      reduce the accuracy of myocardial perfusion imaging. Although it has long been
      assumed that patient obesity effects accuracy, this has never been formally
      evaluated. We studied the effects of patient obesity, defined as a body mass
      index (BMI) > or = 30, on 607 patients who underwent exercise thallium-201 single
      photon emission computed tomography (SPECT). Because the effects of obesity are
      most likely mediated through increased photon attenuation and scatter, we also
      evaluated the effects of other markers of patient size: body surface area (BSA)
      and patient weight. Accuracy was determined by performing quantitative analysis
      and measuring the area under the receiver operating characteristic curve (AUC).
      Obesity was associated with significantly lower accuracy (AUC 0.86 +/- 0.03 vs
      0.92 +/- 0.02, p <0.05) despite similar estimates of maximal coronary blood flow
      (as estimated by heart rate and rate-pressure product at peak exercise) and
      severity of coronary disease. There were no significant differences attributable
      to either patient weight or BSA. Weight and BSA correlated significantly with
      left ventricular chamber size whereas BMI did not. We conclude that the accuracy
      of quantitative SPECT thallium-201 is significantly reduced by patient obesity
      and that although BSA and weight are also associated with increased attenuation,
      they have no effect on accuracy, which is most likely due to the compensating
      effects of increased chamber size.

PMID- 12000053
TI  - Gender differences in triggering of acute myocardial infarction.
AB  - The frequencies of potential triggers of acute myocardial infarction differ
      between men and women. There is a possibility that anti-ischemic drugs protect
      against trigger-related infarctions.

PMID- 12000054
TI  - Frequency of left ventricular free-wall rupture in patients with acute myocardial
      infarction treated with primary angioplasty.
AB  - A total of 590 patients with myocardial infarction treated with primary
      angioplasty were studied, to assess the incidence and related factors of free
      wall rupture in patients with acute myocardial infarction when treated with
      primary angioplasty. The incidence of free-wall rupture was 2.2% (13 patients);
      this incidence was higher in patients >65 years old, women, nonsmokers, as well
      as in those with anterior location and an initial TIMI grade 0 flow, but it was
      similar in patients with a successful or unsuccessful angiographic result.

PMID- 12000055
TI  - Acute myocardial infarction and vascular remodeling.
AB  - We used intravascular ultrasound to show that outward remodeling predominates in
      lesions responsible for acute myocardial infarction, whereas negative remodeling
      is far more prevalent in lesions responsible for chronic stable angina. The total
      cholesterol:high-density lipoprotein ratio was also strongly correlated with
      outward remodeling.

PMID- 12000056
TI  - Preoperative factors predisposing to early postoperative atrial fibrillation
      after isolated coronary artery bypass grafting.
AB  - An analysis of 183 patients in sinus rhythm who underwent coronary artery bypass
      grafting was conducted to determine the association of multiple preoperative
      factors, including an elevated left ventricular end-diastolic pressure, with
      early postoperative atrial fibrillation. An association with advanced age, a
      history of atrial fibrillation, and preoperative digoxin use was found, but not
      with an elevated left ventricular end-diastolic pressure, irrespective of left
      ventricular systolic function.

PMID- 12000057
TI  - Usefulness of the QTc interval in predicting myocardial ischemia in patients
      undergoing exercise stress testing.
AB  - Prolongation of the QTc interval during stress testing predicts myocardial
      ischemia with a sensitivity of 88% and a specificity of 93%. Measurement of the
      QTc segment should be considered as an adjunctive electrocardiographic variable
      in the interpretation of stress tests and is even useful in patients who are not
      able to achieve the age-predicted target heart rate level.

PMID- 12000058
TI  - Accuracy of a pretest questionnaire in exercise test protocol selection.
AB  - Proper exercise test protocol selection is essential to allow adequate time for
      observation of subjective and physiologic responses to exercise, as well as
      provider-patient interaction and patient comfort. This study evaluates the
      accuracy of a pretest questionnaire in predicting exercise capacity for exercise
      test protocol selection and compares the accuracy of this questionnaire when ramp
      versus step protocols are used.

PMID- 12000059
TI  - Frequency of superior vena cava syndrome following radiofrequency modification of
      the sinus node and its management.
AB  - In a series of 35 consecutive patients, the presence of a permanent pacemaker
      appears to be a strong risk factor for developing superior vena cava syndrome
      after radiofrequency modification of the sinus node. Treatment of this
      complication with balloon venoplasty is as effective as surgical repair.

PMID- 12000060
TI  - Acute complications of permanent pacemaker implantation: their financial
      implication and relation to volume and operator experience.
AB  - Complication rates after pacemaker implantation decline after increasing operator
      experiences (total cases), activity (cases per year), and facility with cephalic
      vein cutdown technique. The incremental cost of care is driven by hospital
      resource utilization and does not parallel medical severity.

PMID- 12000061
TI  - Serum profiles of granulocyte-macrophage colony-stimulating factor and C-C
      chemokines in hypertensive patients with or without significant hyperlipidemia.
AB  - The present study investigates the differences in serum activity of granulocyte
      macrophage colony-stimulating factor, macrophage chemoattractant protein-1, and
      macrophage inflammatory protein-1alpha between hypertensive patients with and
      without significant hyperlipidemia before receiving any medical treatment. The
      serum activity of the studied inflammatory factors is more elevated in
      hypertensive patients with significant hyperlipidemia and may be associated with
      atherosclerotic inflammatory process induced by the coexistence of 2 major
      cardiovascular risk factors.

PMID- 12000062
TI  - Influence of aortopulmonary rotation on the anomalous coronary artery pattern in
      tetralogy of fallot.
AB  - Three main patterns of aortic sinus rotation were defined on 517 lateral
      angiograms of tetralogy of Fallot with 14 cases of anomalous coronary artery
      pattern occurring only in patients with a right anterior or right lateral aorta.
      The significant dependence of coronary artery types on the aortic sinus pattern
      made it possible to predict the predisposing coronary artery pattern in tetralogy
      of Fallot based on the aortic sinus pattern.

PMID- 12000063
TI  - Plasminogen activator inhibitor type 1 in adults with Down syndrome and
      protection against macrovascular disease.
AB  - In the present study we have shown that adults with Down syndrome have reduced
      plasminogen activator inhibitor type-1 in blood compared with control subjects
      matched for age, gender, and body mass. Reduced plasminogen activator inhibitor
      type-1 may explain the low incidence of atherosclerotic vascular disease and its
      complications that are attributable to plaque instability, such as myocardial
      infarction and unstable angina, in subjects with Down syndrome, despite an ever
      increasing life expectancy.

PMID- 12000064
TI  - Evidence of a role of endogenous estrogen in the modulation of autonomic nervous
      system.
AB  - We studied heart rate variability in 14 healthy women before and after
      oophorectomy compared with 14 matched women who underwent hysterectomy with
      ovarian conservation. Surgical menopause induced a decline in cardiac vagal
      modulation with a shift toward sympathetic hyperactivity. Recovery of the
      baseline condition after 3 months of estrogen replacement therapy in
      oophorectomized women suggests a role of estrogen in the autonomic nervous
      control of the cardiovascular system.

PMID- 12000065
TI  - Impaired glucose tolerance as a determinant of early deterioration of left
      ventricular diastolic function in middle-aged healthy subjects.
AB  - To clarify the determinants of an abnormal relaxation diastolic pattern assessed
      by Doppler echocardiography, 131 middle-aged healthy subjects were analyzed. By
      multivariate logistic regression analysis, fasting insulin levels (p = 0.0016)
      and peak glucose levels (p = 0.046) were independent predictors of an abnormal
      relaxation diastolic pattern 2 hours after 75 g OGTT.

PMID- 12000066
TI  - Prognosis of aortic intramural hemorrhage compared with classic aortic
      dissection.
AB  - Aortic intramural hemorrhage occurs fairly frequently among patients with aortic
      dissection, and may not have a poor prognosis if it is Stanford type B. In
      patients with type A aortic dissection, cardiac tamponade should be ruled out
      during observation.

PMID- 12000067
TI  - Usefulness of harmonic imaging for left ventricular opacification and endocardial
      border delineation by optison.
AB  - Harmonic and fundamental imaging techniques were directly compared in 20 patients
      undergoing intravenous contrast echocardiography for enhancement of left
      ventricular endocardial border definition. Harmonic imaging demonstrated
      significantly enhanced left ventricular endocardial border detection and improved
      the duration and intensity of a contrast effect despite a reduced dosing
      requirement.

PMID- 12000068
TI  - Case 5: atrial fibrillation after coronary artery bypass grafting.

PMID- 12000069
TI  - Value of "borderline" troponin T measurements in patients with chest pain.

PMID- 12000070
TI  - Monocyte chemoattractant protein-1 and coronary artery disease.
AB  - The designation of atherosclerosis as a chronic inflammatory process represents
      an exciting and logical paradigm shift for cardiologists. Monocyte
      chemoattractant protein-1 (MCP-1) plays an important role in the recruitment and
      activation of monocytes and thus in the development of atherosclerosis. Enhanced
      MCP-1 expression has been detected in macrophages, endothelial cells, and
      vascular smooth muscle cells in the atheromatous plaque. Activation of
      macrophages by MCP-1 also appears to be involved in the vulnerability of the
      plaque. Indeed, circulating MCP-1 levels are elevated in patients with acute
      myocardial infarction and in those with unstable angina, but not in patients with
      stable angina. Production of MCP-1 and macrophage accumulation are also observed
      after coronary angioplasty or grafting, indicating that MCP-1 expression may be
      related not only to instability of atheromatous plaques, but also to the
      formation of restenotic lesions. The development of therapeutic drugs for
      atherosclerosis targeted specially against MCP-1 may be useful in the prevention
      of plaque formation and future myocardial infarction.

PMID- 12000071
TI  - Clinical presentation, hospital length of stay, and readmission rate in patients
      with heart failure with preserved and decreased left ventricular systolic
      function.
AB  - BACKGROUND: Congestive heart failure is the leading cause of hospital admissions
      for adults in the United States. To our knowledge, there are limited data
      comparing the clinical presentation, hospital length of stay, and readmission in
      patients with preserved and decreased left ventricular (LV) systolic function.
      HYPOTHESIS: The goal of the study was to determine whether there are differences
      in clinical presentation, hospital length of stay, and readmission in patients
      with preserved (> or = 50%) and reduced (< 50%) systolic function. METHODS: We
      prospectively evaluated 187 patients admitted with congestive heart failure
      confirmed by the presence of pulmonary vascular congestion on chest x-ray, and
      with recent (< 6 months) documentation of LV systolic function by two-dimensional
      echocardiography. History and physical examination findings, patient
      demographics, comorbidities, discharge medications, and length of hospital stay
      data were documented. Readmission rate over a 6-month follow-up period was also
      documented. RESULTS: Of the 187 patients, 130 (70%) patients had an ejection
      fraction (EF) <50%, and 57 (30%) patients had an EF > or = 50%. Patients with EF
      < 50% were more likely to be men (54 vs. 37%, p = 0.03). African Americans (79
      vs. 60%, p = 0.007), had a higher prevalence of previous stroke (17 vs. 5%, p =
      0.03), and were more likely to carry no medical insurance at the time of
      admission (14 vs. 2%, p = 0.01) and to be discharged on digoxin (60 vs.30%,
      p<0.001). There were no significant differences in symptoms (exertional dyspnea,
      rest dyspnea, orthopnea, or paroxysmal nocturnal dyspnea), or in physical
      examination findings (S3, S4, elevated jugular venous pressure, rales, or
      peripheral edema). According to chest x-ray, patients with EF <50% had more
      frequent cardiomegaly (88 vs. 72% p = 0.008), but there were no differences in
      the presence of pleural effusion or pulmonary vascular congestion (p = NS). The
      mean length of stay was 5.9 and 5.2 days, respectively (p = 0.34). During the 6
      month follow-up period, the readmission rates were 33% (43 patients) and 26% (15
      patients), respectively (p = 0.36). CONCLUSION: The clinical presentation,
      hospital length of stay, and readmission rate for congestive heart failure are
      similar in patients with preserved and decreased LV systolic function.

PMID- 12000072
TI  - Shear-induced platelet aggregation increases in patients with proximal and severe
      coronary artery stenosis.
AB  - BACKGROUND: Shear stress generated in stenosed arteries promotes platelet thrombi
      formation at the stenosed sites by accelerating the binding of von Willebrand
      factor (vWF) to platelets. Shear-induced platelet aggregation (SIPA) has been
      studied in acute coronary syndromes, but not in chronic coronary disease.
      HYPOTHESIS: We investigated the effect of both the site and severity of coronary
      stenosis on SIPA in patients with chronic coronary artery disease. METHODS: Shear
      induced platelet aggregation was measured using platelet-rich plasma in 49
      patients (41 men and 8 women; mean age 61+/-10 years) with coronary artery
      disease to evaluate the association between the extent of SIPA and coronary
      angiographic findings. Stenoses > 75% were considered severe. In all, 62 healthy
      individuals (54 men and 18 women; mean age 45+/-7 years) served as controls. The
      correlation between SIPA and the site and severity of the coronary lesion, and
      parameters of coagulation and fibrinolysis were evaluated. RESULTS: Shear-induced
      platelet aggregation was increased in the stenosis group (69.0+/-10.6%) compared
      with the controls (57.7+/-10.3%, p < 0.0001). Patients with severe stenosis in
      the proximal segments had significantly increased SIPA (p< 0.0001) and vWF larger
      multimer concentration (p<0.0001) compared with the control group. A significant
      correlation existed between SIPA and the vWF larger multimer concentration in all
      subjects studied (r = 0.422, p < 0.0001). CONCLUSIONS: Shear-induced platelet
      aggregation is increased in patients with severe stenosis of the proximal
      coronary arteries and correlates with plasma concentrations of vWF larger
      multimers, suggesting that severe stenosis in the proximal segments is not only
      associated with an increased risk of significant myocardial ischemia, but may
      also generate high shear stress in the stenosed artery and increase plasma vWF
      larger multimers, thereby promoting the formation of platelet thrombi.

PMID- 12000073
TI  - Exaggerated carotid sinus massage responses are related to severe coronary artery
      disease in patients being evaluated for chest pain.
AB  - BACKGROUND: Previous studies have reported that carotid sinus massage responses
      are associated with advancing age and carotid or coronary artery disease.
      HYPOTHESIS: This study was undertaken to investigate the potential role of
      carotid sinus hypersensitivity as a marker for the presence of coronary artery
      disease, and especially left main stem disease, in patients who were referred for
      evaluation of chest pain. METHODS: Toward this end, carotid sinus stimulation
      with simultaneous recordings of the electrocardiogram and aortic pressure was
      performed before coronary arteriography in 150 selected consecutive patients
      (mean age 59.4+/-9 years) who were referred for evaluation of chest pain.
      RESULTS: Coronary artery disease was present in 118 patients (78.7%); of these,
      35 had single-vessel disease, 35 had double-vessel disease, 33 had triple-vessel
      disease, and 15 had left main stem with or without such vessel disease. Carotid
      sinus hypersensitivity was found in 40 patients (26.6%). The incidence of
      hypersensitivity in patients with single-, double-, or triple-vessel disease and
      left main stem disease was 8.5, 14.2, 57.5, and 73.3%, respectively. Stepwise
      multiple logistic regression analysis revealed that left main stem disease was
      significantly and independently related to the presence of carotid sinus
      hypersensitivity (p < 0.05). In addition, the presence of hypersensitivity had
      73.3% sensitivity, 86.2% specificity, and 96.3% negative predictive value for the
      presence of left main stem disease. CONCLUSION: In patients being evaluated for
      suspected ischemic heart disease, carotid sinus massage responses are related to
      severe coronary disease. The absence of hypersensitivity may reflect absence of
      left main stem disease.

PMID- 12000074
TI  - Conjugated estrogen administration improves common carotid artery elastic
      properties in normotensive postmenopausal women.
AB  - BACKGROUND: Various vascular effects of estrogens have been proposed to explain
      further the beneficial effect of replacement therapy in cardiovascular events.
      HYPOTHESIS: The study was undertaken to assess the effect of conjugated estrogen
      on the elastic properties of the large arteries in normotensive, healthy,
      postmenopausal women. METHODS: Toward this end, we investigated the acute effect
      of conjugated estrogen on the elastic properties of the common carotid artery
      (CCA) in 20 normotensive, healthy, postmenopausal women (age 54+/-3 years) at
      baseline and 20 min after the intravenous administration of 1.25 mg conjugated
      estrogens. The CCA distensibility was derived by a combination of surface
      ultrasonographic data and simultaneous blood pressure measurements at the
      brachial artery. The carotid pulsatility index, a measure of brain impedance, was
      determined electronically by tracing the CCA Doppler waveform. RESULTS: At
      baseline, CCA distensibility had a negative correlation with both patients' age
      and time since menopause (r = -0.57 and r = -0.48, p < 0.05 for both cases).
      After estrogen administration, estradiol and estrone plasma levels were restored
      to the range of usual premenopausal values. Estrogen induced a significant
      increase in CCA distensibility by 0.92+/-0.005 dyne(-1) x cm2 x 10(-6) (from 2.03
      to 2.95 dyne(-1) x cm2 x 10(-6)) and a significant reduction in CCA pulsatility
      index by 0.24+/-0.06, (from 2.17 to 1.93) (p < 0.001 for both cases). The
      improvement in CCA distensibility had a negative correlation with both patients'
      age and time since menopause (r= -0.46 and r = -0.44, respectively, p < 0.05 for
      both cases). CONCLUSIONS: Acute conjugated estrogen administration induced an
      improvement in CCA elasticity and a reduction in brain impedance in normotensive,
      postmenopausal women. As the age of women and the time since menopause increased,
      the improvement in carotid distensibility decreased in such selected subjects.

PMID- 12000075
TI  - The effect of aortic valve replacement on N-terminal natriuretic propeptides in
      patients with aortic stenosis.
AB  - BACKGROUND: Increased plasma concentrations of natriuretic peptides have been
      demonstrated to be associated with increased intracardiac pressure and left
      ventricular (LV) hypertrophy. After aortic valve replacement (AVR) in aortic
      stenosis patients, there is a relief of the left outflow obstruction with a
      substantial hemodynamic improvement. This is followed by a gradual regression of
      the LV hypertrophy. HYPOTHESIS: After AVR, reduction in LV filling pressure is
      expected to occur rapidly, while regression of LV hypertrophy will take place
      over a longer time period. On this basis we hypothesized that the plasma levels
      of N-terminal proatrial natriuretic peptide (NT-proANP) would be reduced early in
      the postoperative period, while N-terminal probrain natriuretic peptide (NT
      proBNP), through its closer reflection of LV hypertrophy, would be sustained for
      a longer period. METHODS: Two groups of patients with aortic stenosis undergoing
      AVR were followed for 4 and 12 months, respectively. Plasma concentrations of NT
      proANP and NT-proBNP were measured before and after AVR and related to
      preoperative findings and changes in the aortic valve area index. RESULTS: Before
      AVR, the patients had significantly increased plasma levels of NT-proANP and NT
      proBNP. After AVR, NT- proANP was decreased at 4 and 12 months but remained
      elevated compared with controls. N-terminal-proBNP tended to decrease, but did
      not change significantly. When the patients were followed for 12 months, only
      those with elevated preoperative pulmonary capillary wedge pressure had decreased
      peptide levels (NT-proANP: p = 0.017, NT-proBNP: p = 0.058). There was no
      regression of LV hypertrophy. The patients with the largest postoperative valve
      area index [1.27 (1.10-1.55) cm2/m2] had the largest reduction of NT-proBNP
      (47%). Those with the smallest valve area index [0.67 (0.54-0.73) cm2/m2] had no
      decrease in NT-proBNP. CONCLUSIONS: Our study suggests that a reduction in left
      atrial pressure is the main factor causing the change of NT-proANP level after
      AVR. A small prosthetic valve orifice area with a high aortic valve gradient
      might prevent regression of LV hypertrophy, thus representing a stimulus for
      increased cardiac secretion of NT-proBNP.

PMID- 12000076
TI  - The impact of right atrial ischemia on inferior myocardial infarction with
      extension to right ventricle: transesophageal echocardiographic examination.
AB  - BACKGROUND: The role of the right atrium in adaptation to the hemodynamic changes
      produced by extension of myocardial infarction (MI) of the left ventricular
      inferior wall to the right ventricle is fundamental. HYPOTHESIS: The aim of this
      study was analyze a group of patients with MI with extension of right chambers,
      and particularly right atrial alterations, by transesophageal echocardiography
      and to correlate it with clinical and angiographic variables. METHODS: Thirty
      patients with right ventricular (RV) MI involving obstruction of the right
      coronary artery without stenosis of the left coronary artery were included; 18
      underwent early reperfusion. Transesophageal echocardiography was performed on
      all within 5 days of coronary angiography. Follow-up was continued from
      hospitalization to the present. RESULTS: When patients with right atrial ischemia
      were compared with those with normal right atrium, the RV wall movement score was
      significantly greater in the group with right atrial ischemia, severe RV
      dilatation was more frequent, and association with proximal occlusion of the
      artery responsible for the MI, as well as absence of right atrial branches and
      poor collateral circulation, were significant. Hospitalization was more prolonged
      in this group, and there was a higher incidence of arrhythmias, complete
      atrioventricular block, and mortality. CONCLUSIONS: Right atrial ischemia
      associated with RV infarction leads to a higher incidence of complications and
      higher mortality. Transesophageal echocardiography is a safe, reproducible
      technique that provides detailed anatomic information about right chambers and
      aids in the determination of prognosis and therapeutic decisions.

PMID- 12000077
TI  - New parameters in the interpretation of exercise testing in women: QTc dispersion
      and QT dispersion ratio difference.
AB  - BACKGROUND: It has been reported that the increase of QT dispersion (QTD) that
      occurs due to increased inhomogeneity of the ventricular repolarization because
      of transient ischemia obtained by standard 12-lead electrocardiogram (ECG), the
      changes during exercise, and the differences between exercise and rest increase
      the accuracy of exercise test in the diagnosis of coronary artery disease (CAD).
      HYPOTHESIS: This study was designed to investigate the value of QTD parameters,
      which are reported to increase the diagnostic accuracy of exercise test in women.
      METHODS: Ninety-seven women who had undergone coronary angiography and exercise
      test were evaluated for diagnosis of chest pain. QT dispersion was calculated
      using the measurements of the highest and lowest values of QT interval obtained
      by ECG during peak exercise. The QTc using Bazett's equation, and the QTD ratio
      (QTDR) using QT/RR were calculated, and QTcD and QTD ratios were obtained. The
      difference between QTcD and QTDR was determined by extracting the rest values
      from the exercise values. RESULTS: The groups with normal coronaries (n = 48),
      single-vessel CAD (n = 24), and multivessel CAD (n = 25) were compared. The
      obtained QTD parameters at peak exercise and their differences between exercise
      and rest were found to be significantly increased in patients with CAD (p
      <0.001). Furthermore, these parameters were found to be higher in the patients
      with multivessel CAD than in those with single-vessel disease (p < 0.05). With
      the parameters QTcD > 60 ms and QTDR > 10%, greater sensitivity and specificity
      were obtained compared with ST-segment depression. The highest diagnostic
      accuracy was obtained with the QTD parameters calculated from the differences
      between rest and exercise values. The diagnostic accuracy of the difference of
      QTcD > 15 ms and the difference of QTDR > 5% was relatively higher than the other
      parameters (sensitivity, specificity, and negative and positive predictor values
      are 84, 88, 84, 87% and 84, 96, 85, 95%, respectively). CONCLUSION: The use of
      QTD parameters as variables of ECG, which is easily obtainable in the evaluation
      of exercise ECG in women, increases the diagnostic accuracy of the exercise test.
      In addition, the evaluation of QTD variables may provide information about the
      incidence of CAD.

PMID- 12000078
TI  - Type III hyperlipoproteinemia.

PMID- 12000079
TI  - Severe aortic stenosis and mitral regurgitation in a woman with systemic lupus
      erythematosus.
AB  - Libman-Sacks endocarditis complicating systemic lupus erythematosus has rarely
      been reported to cause hemodynamically significant valvular lesions. This report
      presents a case of severe aortic stenosis combined with severe mitral
      regurgitation associated with systemic lupus erythematosus in a young woman who
      died while on the quota list for surgery.

PMID- 12000080
TI  - Inge Edler: father of echocardiography.

PMID- 12000081
TI  - Citalopram has an antagonistic action on cortical spreading depression in well
      nourished and early-malnourished adult rats.
AB  - Adult, well-nourished (W) and early-malnourished (M) male Wistar rats were
      injected intraperitoneally for 7 days with 20 mg/kg CIT and cortical spreading
      depression (CSD) was recorded for 4 h on the day following the treatment. M
      animals presented lower body weights, as well as higher CSD velocities of
      propagation, than the W ones, as previously reported. Compared to saline-injected
      controls, rats treated with CIT for 7 days presented comparable body weights and
      lower mean CSD velocities, per hour of recording, the differences being
      significant at the second hour (3.29+/-0.31 versus 3.56+/-0.40 mm/min; P < 0.05).
      Topical, cortical application of CIT (1- and 5 mg/ml solutions over the intact
      dura-mater) reduced dose-dependently the CSD velocity (maximal reductions of 16.3
      and 55.8% for the 1 and 5 mg/ml solutions, respectively; P < 0.05), as well as
      the amplitude of the CSD-slow potential change (58.2 and 88.3%). In three out of
      seven W-rats and in one out of seven M-rats, topical CIT (5 mg/ml) blocked CSD
      propagation. The effects were reverted by flushing the treated region with
      saline. In the M-groups, CIT affected CSD in the same manner as in the W ones.
      The results reinforce previous evidence for an antagonistic influence of the
      serotoninergic activity on CSD.

PMID- 12000082
TI  - Transfer ribonucleic acid charging in rat brain after consumption of amino acid
      imbalanced diets.
AB  - Recognition of an amino acid-imbalanced diet (IMB) is thought to occur in the
      anterior piriform cortex (APC) of the brain in response to a decrease in the
      limiting amino acid. We hypothesized that tRNA charging is decreased after
      ingestion of IMB and that this is part of the mechanism by which a decrease in
      the limiting amino acid is recognized. We investigated this question by
      determining levels of charged and uncharged tRNA using the periodate oxidation
      method and also by using high performance liquid chromatography (HPLC) analysis
      of amino acids acylated to brain tRNA. Using the periodate method, we found that
      isoleucyl-tRNA in both whole brain and APC of rats fed an isoleucine-IMB was
      increased, rather than decreased, in comparison to the basal diet and the
      corrected diet. Using HPLC analysis, we found that the absolute amount of tRNA
      charged with the limiting amino acid was not altered by dietary treatment. These
      two experimental approaches measure different aspects of tRNA charging, but the
      results clearly indicate that a reduction in tRNA charging is unlikely to be the
      signal by which a limiting amino acid is recognized in the brain 2 h after
      ingestion of IMB.

PMID- 12000083
TI  - Failure to reduce short-term appetite following alcohol is independent of beliefs
      about the presence of alcohol.
AB  - Previously, it has been reported that energy consumed as alcohol prior to lunch
      does not result in subsequent reductions in voluntary food intake, and in some
      situations alcohol can increase subsequent appetite. The present study extends
      these findings by examining the effects of beliefs about alcohol content.
      Eighteen unrestrained men ate lunch 20 min after a preload of either water, an
      alcoholic beer or a non-alcoholic beer matched for energy content. Food intake
      was significantly less following the non-alcoholic beer than after alcohol or
      water, but when preload energy was included subjects had a higher overall energy
      intake on the day they consumed alcohol compared with both water and no-alcohol
      conditions. There were no significant differences in hunger or fullness ratings
      following the three drinks before or after the test meal, but the specific
      relationship between rated hunger and intake within the test meal was altered by
      the drink manipulation. The rate at which hunger decreased, and fullness
      increased, was slower after alcohol than after water or no-alcohol. The drinks
      did not alter the pleasantness of the test meal or increase hunger at the start
      of eating. When contrasted with previous work, these data confirm that alcohol
      consumed before lunch fails to reduce subsequent food intake, but also suggests
      that changes in rated appetite are influenced by beliefs about alcohol content.

PMID- 12000084
TI  - Stress, breakfast cereal consumption and cortisol.
AB  - Recent research has shown that regular consumption of breakfast cereal is
      associated with lower stress levels and reports of better physical and mental
      health. The present study examined this issue using an objective indicator of
      stress, salivary cortisol. The results showed that stress was associated with
      higher cortisol levels and daily consumption of breakfast cereal was associated
      with lower cortisol levels. Although it was not possible to rule out all the
      alternative explanations of the association between breakfast cereal consumption
      and cortisol, analyses did show that the effect could not be accounted for by
      general health or nutritional status. The effects of breakfast cereal consumption
      and stress were also independent, which shows that the effects of breakfast found
      here cannot be due to stress buffering. Further research manipulating the
      nutrient content of the breakfast cereal is now required to provide further
      information about the mechanisms underlying this effect.

PMID- 12000085
TI  - Stress, breakfast cereal consumption and objective signs of upper respiratory
      tract illnesses.
AB  - Recent research has shown that both negative life events and breakfast cereal
      consumption are associated with the incidence and severity of subjective symptoms
      of upper respiratory tract illnesses (URTIs) Two studies were conducted to
      examine whether objective markers of illness were also associated with stress and
      breakfast cereal consumption. The results from the first study showed that
      regular breakfast cereal consumption was associated with lower sub-lingual
      temperatures in volunteers with URTIs. Stress had no effect on temperature. In
      the second study nasal secretion weight was lower in regular breakfast cereal
      consumers but was not influenced by stress. These studies suggest that breakfast
      cereal consumption is associated with reduced illness severity and that this does
      not reflect stress levels. Further research is now required to determine whether
      such results are directly due to cereal consumption or reflect correlated
      attributes, such as other aspects of the diet.

PMID- 12000086
TI  - Taurine: evidence of physiological function in the retina.
AB  - Taurine is a free amino acid found in high millimolar concentrations in mammalian
      tissue and is particularly abundant in the retina. Mammals synthesize taurine
      endogenously with varying abilities, with some species more dependent on dietary
      sources of taurine than others. Human children appear to be more dependent on
      dietary taurine than adults. Specifically, it has been established that visual
      dysfunction in both human and animal subjects results from taurine deficiency.
      Moreover, the deficiency is reversed with simple nutritional supplementation with
      taurine. The data suggest that taurine is an important neurochemical factor in
      the visual system. However, the exact function or functions of taurine in the
      retina are still unresolved despite continuing scientific study. Nevertheless,
      the importance of taurine in the retina is implied in the following experimental
      findings: (1) Taurine exhibits significant effects on biochemical systems in
      vitro. (2) The distribution of taurine is tightly regulated in the different
      retinal cell types through the development of the retina. (3) Taurine depletion
      results in significant retinal lesions. (4) Taurine release and uptake has been
      found to employ distinct regulatory mechanisms in the retina.

PMID- 12000087
TI  - Pre- and post-natal protein malnutrition alters the effect of rapid eye movements
      sleep-deprivation by the platform-technique upon the electrocorticogram of the
      circadian sleep-wake cycle and its frequency bands in the rat.
AB  - Selective deprivation of paradoxical (or rapid eye movements) sleep (REMS) in
      protein malnourished young male rats, results in circadian and homeostatic
      alterations. By means of electrocorticographic recordings, we have examined the
      sleep-wake cycle as a functional maturity index, and its circadian and
      homeostatic mechanisms in prenatal (PM) and chronically (CM) protein malnourished
      young male rats. The effects of rapid eye movements sleep-deprivation (REMS-D),
      by the platform technique in a "conflict experiment" (i.e. recovery from REMS-D
      begun during the circadian phase of activity), revealed that in PM animals, wake
      (WAK) was increased significantly during recovery days 1 and 2 (RD1, RD2); and
      slow wave sleep (SWS) was reduced significantly during these days. Prenatal
      protein-malnutrition altered the phase of WAK and REMS rhythms, and the amplitude
      of SWS rhythm was decreased. The REMS compensatory increase after REMS-D (REMS
      rebound) was confined to the first 4-h block of the activity phase in all
      experimental groups and 24 h later another REMS rebound was displayed in PM
      animals. The paradoxical sleep-rebound in CM animals was significantly higher
      than control and PM rats and it was only shown at the first 4-h block after REMS
      D. Before and after REMS-D the circadian distribution of both sleep states, and
      the electrocortical frequency bands showed different circadian phases at the same
      day-time in control, PM and CM rats. The aforementioned indicates that protein
      malnutrition exerts important effects on the circadian and homeostatic mechanisms
      driving sleep. Therefore, the temporal structure of the malnourished rats may not
      allow proper synchronization of some sleep parameters, particularly REMS, to the
      environmental time cues.

PMID- 12000088
TI  - Influence of rate-limited sorption on the cleanup of layered soils by vapor
      extraction.
AB  - The conditions under which rate-limited sorption is important for cleanup of
      layered soils by vapor extraction are investigated. The investigation includes
      two steps: (a) the cleanup time is estimated for a number of scenario cases by
      means of a numerical model and (b) the numerical results are approximated using
      analytical solutions derived for simplified models. In this way, equations are
      derived, which give insight into the influence of different parameters
      characterizing the properties of the soil, the geometry of the formation, the
      mass transfer mechanisms in it, and the distribution of the contaminant mass in
      the different phases (gas phase, water phase and solid phase). The numerical
      model used is based on the advection-dispersion differential equations for
      Darcian isothermal airflow, local equilibrium contaminant mass transfer between
      gas phase and soil water and first-order kinetics for mass transfer between soil
      water and solid phase. The numerical results are approximated combining an
      analytical solution to estimate cleanup time in layered formations for local
      equilibrium sorption, which has been presented in a previous work (J. Contam.
      Hydrol., 36 (1999) 105). with an analytical solution based on the well-mixed
      reservoir model under consideration of rate-limited sorption. The analytical
      approximation of the cleanup time is in reasonable agreement with the numerical
      results and allows its estimation with small computational effort.

PMID- 12000089
TI  - Kinetic modeling of virus transport at the field scale.
AB  - Bacteriophage removal by soil passage in two field studies was re-analyzed with
      the goal to investigate differences between one- and two-dimensional modeling
      approaches, differences between one- and two-site kinetic sorption models, and
      the role of heterogeneities in the soil properties. The first study involved
      removal of bacteriophages MS2 and PRDI by dune recharge, while the second study
      represented removal of MS2 by deep well injection. In both studies, removal was
      higher during the first meters of soil passage than thereafter. The software
      packages HYDRUS-ID and HYDRUS-2D, which simulate water flow and solute transport
      in one- and two-dimensional variably saturated porous media, respectively, were
      used. The two codes were modified by incorporating reversible adsorption to two
      types of kinetic sites. Tracer concentrations were used first to calibrate flow
      and transport parameters of both models before analyzing transport of
      bacteriophages. The one-dimensional one-site model did not fully describe the
      tails of the measured breakthrough curves of MS2 and PRD1 from the dune recharge
      study. While the one-dimensional one-site model predicted a sudden decrease in
      virus concentrations immediately after the peaks, measured data displayed much
      smoother decline and tailing. The one-dimensional two-site model simulated the
      overall behavior of the breakthrough curves very well. The two-dimensional one
      site model predicted a more gradual decrease in virus concentrations after the
      peaks than the one-dimensional one-site model, but not as good as the one
      dimensional two-site model. The dimensionality of the problem hence can partly
      explain the smooth decrease in concentration after peak breakthrough. The two
      dimensional two-site model provided the best results. Values for k(att2) and
      k(det2) could not be determined at the last two of four monitoring wells, thus
      suggesting that either a second type of kinetic sites is present in the first few
      meters of dune passage and not beyond the second monitoring well, or that effects
      of soil heterogeneity and dimensionality of the problem overshadowed this
      process. Variations between single collector efficiencies were relatively small,
      whereas collision efficiencies varied greatly. This implies that the nonlinear
      removal of MS2 and PRD1 is mainly caused by variations in interactions between
      grain and virus surfaces rather than by physical heterogeneity of the porous
      medium. Similarly, a two-site model performed better than the one-site model in
      describing MS2 concentrations for the deep well injection study. However, the
      concentration data were too sparse in this study to have much confidence in the
      fitted parameters.

PMID- 12000090
TI  - Influence of hydrological and geochemical processes on the transport of chelated
      metals and chromate in fractured shale bedrock.
AB  - Field-scale processes governing the transport of chelated radionuclides in
      groundwater remain conceptually unclear for highly structured, heterogeneous
      environments. The objectives of this research were to provide an improved
      understanding and predictive capability of the hydrological and geochemical
      mechanisms that control the transport behavior of chelated radionuclides and
      metals in anoxic subsurface environments that are complicated by fracture flow
      and matrix diffusion. Our approach involved a long-term, steady-state natural
      gradient field experiment where nonreactive Br- and reactive 57Co(II)EDTA2-
      109CdEDTA2-, and 51Cr(VI) were injected into a fracture zone of a contaminated
      fractured shale bedrock. The spatial and temporal distribution of the tracer and
      solutes was monitored for 500 days using an array of groundwater sampling wells
      instrumented within the fast-flowing fracture regime and a slower flowing matrix
      regime. The tracers were preferentially transported along strike-parallel
      fractures coupled with the slow diffusion of significant tracer mass into the
      bedrock matrix. The chelated radionuclides and metals were significantly retarded
      by the solid phase with the mechanisms of retardation largely due to redox
      reactions and sorption coupled with mineral-induced chelate-radionuclide
      dissociation. The formation of significant Fe(III)EDTA byproduct that accompanied
      the dissociation of the radionuclide-chelate complexes was believed to be the
      result of surface interactions with biotite which was the only Fe(III)-bearing
      mineral phase present in these Fe-reducing environments. These results counter
      current conceptual models that suggest chelated contaminants move conservatively
      through Fe-reducing environments since they are devoid of Fe-oxyhydroxides that
      are known to aggressively compete for chelates in oxic regimes. Modeling results
      further demonstrated that chelate-radionuclide dissociation reactions were most
      prevalent along fractures where accelerated weathering processes are expected to
      expose more primary minerals than the surrounding rock matrix. The findings of
      this study suggest that physical retardation mechanisms (i.e. diffusion) are
      dominant within the matrix regime, whereas geochemical retardation mechanisms are
      dominant within the fracture regime.

PMID- 12000091
TI  - Microbially mediated redox processes in natural analogues for radioactive waste.
AB  - Natural analogues allow scientists to investigate biogeochemical processes
      relevant to radioactive waste disposal that occur on time scales longer than
      those that may be studied by time-limited laboratory experiments. The Palmottu U
      Th deposit in Finland and the Bangombe natural nuclear reactor in Gabon involve
      the study of natural uranium, and are both considered natural analogues for
      subsurface radioactive waste disposal. The microbial population naturally present
      in groundwater may affect the redox conditions, and hence, the radionuclide
      solubility and migration. Therefore, groundwater samples from the two sites were
      investigated for microbial populations. The total numbers of cells ranged from
      10(4) to 10(6) cells ml(-1). Iron-reducing bacteria (IRB) were the largest
      culturable microbial population in the Palmottu groundwater and were present at
      up to 1.3 x 10(5) cells ml(-1). Sulfate-reducing bacteria (SRB) and acetogens
      could also be cultured from the Palmottu groundwater. The numbers of IRB and SRB
      were largest in groundwater with the lowest uranium concentrations. Removal of
      dissolved U(VI) from solution was concomitant with the growth of IRB enrichment
      cultures and the reduction of iron. The redox buffer in the Palmottu groundwater
      consists of iron and uranium species, both of which are affected by IRB. IRB and
      aerobic heterotrophs were cultured from the Bangombe groundwater, where redox
      potentials are buffered by iron and organic carbon species. Microbial populations
      similar to those found at Palmottu and Bangombe are found throughout the
      Fennoscandian Shield, a potential host rock for subsurface radioactive waste
      disposal. These results confirm that microorganisms can be expected to play a
      role in stabilizing radioactive waste disposed of in the subsurface by lowering
      redox potential and immobilizing radionuclides.

PMID- 12000092
TI  - Nitrate-enhanced bioremediation of BTEX-contaminated groundwater: parameter
      estimation from natural-gradient tracer experiments.
AB  - Two natural-gradient pulse tracer tests were conducted in a petroleum
      contaminated aquifer to evaluate the potential for benzene, toluene,
      ethylbenzene, and xylenes (BTEX) biodegradation under enhanced nitrate-reducing
      conditions. Addition of nitrate resulted in loss of toluene, ethylbenzene, and
      m,p-xylenes (TEX) after an initial lag period of approximately 9 days. Losses of
      benzene were not observed over the 60-day monitoring period. Tracer breakthrough
      curves (BTCs) were analyzed to derive transport and biodegradation parameters,
      including advective velocities, retardation factors, dispersion coefficients,
      biodegradation rate constants, and nitrate utilization ratios. Using the
      parameters derived from the BTC analysis, numerical simulations of one of the
      tracer experiments were conducted using BIONAPL/3D [Molson, J., BIONAPL/3D User
      Guide, A 3D Coupled Flow and Multi-Component Reactive transport model. University
      of Waterloo, Waterloo, Ontario, Canada]. Simulations using the BTC-derived
      transport and biodegradation parameters successfully reproduced benzene, TEX, and
      nitrate concentrations measured during the tracer experiment. Comparisons of
      observed and simulated nitrate concentrations indicate that the mass ratio of
      nitrate-N utilized to TEX degraded increased over time during the experiment,
      reaching values many times that expected based on stoichiometry of TEX oxidation
      coupled to nitrate reduction. Excess nitrate loss is likely due to oxidation of
      other organics in addition to TEX.

PMID- 12000093
TI  - Bioenhancement of NAPL pool dissolution: experimental evaluation.
AB  - Experiments were conducted to quantify nonaqueous phase liquid (NAPL) pool
      dissolution and its enhancement by in situ biodegradation. The experiments were
      performed using square cross-section, glass-bead packed column reactors with a
      small pool of a toluene-in-dodecane mixture (toluene mole fraction, X(tol)
      approximately 0.02 or 0.09). Experimental quasi-steady-state toluene dissolution
      fluxes were determined using a 14C-carbon mass-balance approach during water
      flushing with and without biodegradation. The experiments demonstrated a
      statistically significant bioenhancement of the toluene dissolution flux of up to
      roughly twofold at average pore water velocities of approximately 0.1 and 1 m/day
      when the toluene mole fraction was low ( approximately 0.02); however, little or
      no bioenhancement was observed with the higher mole fraction ( approximately
      0.09). Although it cannot be determined conclusively, the weight of evidence
      based on biomass measurements and model analyses suggests that the reduced
      bioenhancement for the high mole fraction was due to higher dissolved toluene
      concentrations, which may have caused toxicity effects. Importantly, even though
      NAPL dissolution was not bioenhanced in every case, the biodegradation reduced
      toluene concentrations to low levels in the reactor effluents.

PMID- 12000094
TI  - An in situ study of the role of surface films on granular iron in the permeable
      iron wall technology.
AB  - Permeable walls of granular iron are a new technology developed for the treatment
      of groundwater contaminated with dissolved chlorinated solvents. Degradation
      ofthe chlorinated solvents involves a charge transfer process in which they are
      reductively dechlorinated, and the iron is oxidized. The iron used in the walls
      is an impure commercial material that is covered with a passive layer of Fe2O3,
      formed as a result of a high-temperature oxidation process used in the production
      of iron. Understanding the behaviour of this layer upon contact with solution is
      important, because Fe2O3 inhibits mechanisms involved in contaminant reduction,
      including electron transfer and catalytic hydrogenation. Using a glass column
      specially designed to allow for in situ Raman spectroscopic and open circuit
      potential measurements, the passive layer of Fe2O3 was observed to be largely
      removed from the commercial product, Connelly iron, upon contact with Millipore
      water and with a solution of Millipore water containing 1.5 mg/l
      trichloroethylene (TCE). It has been previously shown that Fe2O3 is removed from
      iron surfaces upon contact with solution by an autoreduction reaction; however,
      prior to this work, the reaction has not been shown to occur on the impure
      commercial iron products used in permeable granular iron walls. The rate of
      removal was sufficiently rapid such that the initial presence of Fe2O3 at the
      iron surface would have no consequence with respect to the performance of an in
      situ wall. Subsequent to the removal of Fe2O3 layer, magnetite and green rust
      formed at the iron surface as a result of corrosion in both the Millipore water
      and the solution containing TCE. The formation of these two species, rather than
      higher valency iron oxides and oxyhydroxides, is significant for the technology.
      The former can interfere with contaminant degradation because they inhibit
      electron transfer and catalytic hydrogenation. Magnetite and green rust, in
      contrast, will not inhibit the mechanisms involved in contaminant reduction, and
      hence their formation is beneficial to the long-term performance of the iron
      material.

PMID- 12000095
TI  - Targeted expression of tetanus toxin: a new tool to study the neurobiology of
      behavior.
AB  - Over the past few decades, the explosion of molecular genetic knowledge,
      particularly in the fruit fly Drosophila melanogaster, has led to the
      identification of a large number of genes, which, when mutated, directly or
      indirectly affect fly behavior. Beyond the genetic and molecular characterization
      of genes and their associated molecular pathways, recent advances in molecular
      genetics also have allowed the development of new tools dedicated more directly
      to the dissection of the neural bases for various behaviors. In particular, the
      conjunction of the development of two techniques--the enhancer-trap detection
      system and the targeted gene expression system, based on the yeast GAL4
      transcription factor--has led to the development of the binary enhancer-trap
      P[GAL4] expression system, which allows the selective activation of any cloned
      gene in a wide variety of tissue- and cell-specific patterns. Thus, this
      development, in addition to allowing the anatomical characterization of neuronal
      circuitry, also allows, via the expression of tetanus toxin light chain (known to
      specifically block synaptic transmission), an investigation of the role of
      specific neurons in certain behaviors. Using this system of "toxigenetics,"
      several forms of behavior--from those mediated by sensory systems, such as
      olfaction, mechanoreception, and vision, to those mediated by higher brain
      function, such as learning, memory and locomotion--have been studied. These
      studies aim to map neuronal circuitry underlying specific behaviors and thereby
      unravel relevant neurophysiological mechanisms. The advantage of this approach is
      that it is noninvasive and permits the investigation of behavior in the free
      moving animal. We review a number of behavioral studies that have successfully
      employed this toxigenetic approach, and we hope to persuade the reader that
      transgenic tetanus toxin light chain is a useful and appropriate tool for the
      armory of neuroethologists.

PMID- 12000096
TI  - Evolutionary behavioral genetics in Drosophila.
AB  - Behavioral genes have a special evolutionary interest because they are
      potentially involved in speciation and in many forms of adaptation. Dozens of
      loci affecting different aspects of behavior have been already identified and
      cloned in Drosophila. Some of these genes determine variation in such
      ethologically complex phenotypes as the male "love song" that is produced during
      courtship and the locomotor "sleep-wake" activity cycles that are controlled by
      the circadian clock. Although the evolutionary analysis of most behavioral genes
      in Drosophila is relatively new, it has already given important insights into the
      forces shaping the molecular variation at these loci and their functional
      consequences.

PMID- 12000097
TI  - Germline transformants spreading out to many insect species.
AB  - The past 5 years have witnessed significant advances in our ability to introduce
      genes into the genomes of insects of medical and agricultural importance. A
      number of transposable elements now exist that are proving to be sufficiently
      robust to allow genetic transformation of species within three orders of insects.
      In particular all of these transposable elements can be used genetically to
      transform mosquitoes. These developments, together with the use of suitable genes
      as genetic markers, have enabled several genes and promoters to be transferred
      between insect species and their effects on the phenotype of the transgenic
      insect determined. Within a very short period of time, insights into the function
      of insect promoters in homologous and heterologous insect species are being
      gained. Furthermore, strategies aimed at ameliorating the harmful effects of pest
      insects, such as their ability to vector human pathogens, are now being tested in
      the pest insects themselves. We review the progress that has been made in the
      development of transgenic technology in pest insect species and conclude that the
      repertoire of transposable element-based genetic tools, long available to
      Drosophila geneticists, can now be applied to other insect species. In addition,
      it is likely that these developments will lead to the generation of pest insects
      that display a significantly reduced ability to transmit pathogens in the near
      future.

PMID- 12000098
TI  - Genes mediating sex-specific behaviors in Drosophila.

PMID- 12000099
TI  - General practitioners' attitudes and ethical decisions in end-of-life care after
      a year of interactive Internet-based training.
AB  - BACKGROUND: Personal characteristics affect physicians' end-of-life decisions.
      Education in palliative care (PC) faces a challenge in influencing doctors'
      attitudes and decision making in PC. A one-year Internet-mediated education
      project was arranged for general practitioners in Finland to provide postgraduate
      education in PC. METHODS: A questionnaire was sent before and after the project
      to the education group (EG, n = 79) and a control group (CG, n = 100). Treatment
      decisions for presented scenarios and attitudes toward PC were elicited. RESULTS:
      EG doctors had previously participated in postgraduate training in PC more often
      than had CG doctors (93% vs 29%). For a young terminal cancer patient, EG doctors
      chose CPR less often than did CG doctors (7% vs 33%, p = 0.004); 30% of EG
      doctors would have continued antibiotic treatment in the case of a terminal
      cancer patient, vs 55% of CG doctors (p = 0.023). EG doctors more often agreed
      with the statement "Terminal care is satisfying" (p < 0.001). Treatment decisions
      or attitudes did not change significantly in either group during the year, the EG
      doctors were more satisfied with their work after the project. CONCLUSION: There
      are substantial differences in decision making between those who have experience
      and special interest in the subject and those who do not. To achieve the goals of
      education in PC, the most difficult target group, the "silent majority" of
      doctors, should be reached.

PMID- 12000100
TI  - Interactive training for the management of breast cancer in general practice in
      Europe.
AB  - BACKGROUND: General practitioners need to play a more active role in the
      management of patients with breast cancer, specifically in screening programs,
      counseling, follow-up, palliative care, and psychosocial support. Special
      training is needed to meet these demands. METHODS: An interactive training
      program resident on CD-ROM was developed. It includes nine cases designed
      according to the case method and three cases created for group discussions. The
      program also contains a self-test and an encyclopedia with facts and figures
      about breast cancer. The program was tested by 20 trainers/trainees in each of
      four participating countries. RESULTS: The formata, content, and usefulness of
      the program were ranked highly: generally between 4 and 5 on a scale from 1 (low)
      to 5 (high), based on 78 evaluation forms. CONCLUSION: The program seems to be an
      adequate tool for GP training.

PMID- 12000101
TI  - Evaluation of a program to train nurses to screen for breast and cervical cancer
      among Native American women.
AB  - BACKGROUND: Routine screening for breast and cervical cancers lowers mortality
      from these diseases, but the benefit has not permeated to Native American women,
      for whom the five-year survival rate is the lowest of any population group in the
      United States. To help address this problem, an educational/training program was
      designed to enhance the skills of nurses and other health service providers and
      develop clinic support systems to better recruit, screen, and follow clients for
      breast and cervical cancer screening services. METHODS: A total of 131 nurses
      participated in the training program at 33 different sites between 1995 and 2000.
      Prior to and following training, each participant was given a questionnaire to
      determine knowledge of breast and cervical cancer screening techniques and
      recommendations, cancer survival and risk factors, and situational scenarios.
      RESULTS: The average score for the pretest was 54% correct. The posttest average
      was 89% correct. The percent correct increased 35% from pre- to posttest (p <
      0.001). CONCLUSION: The knowledge to implement a successful screening program can
      be acquired through the current curriculum.

PMID- 12000102
TI  - Evaluating information for women referred for breast screening abnormalities.
AB  - BACKGROUND: To evaluate a plain-language guideline sent to women with abnormal
      screening results who attended the Manitoba Breast Screening Program (MBSP).
      METHODS: A plain-language guideline was mailed with a result letter to 258
      randomly chosen women who had abnormal mammograms and/or abnormal clinical breast
      examinations. Four weeks later, a satisfaction questionnaire was mailed to these
      women (cases) as well as to 254 randomly chosen women with abnormal results who
      were not sent a guideline (controls). All cases were interviewed by telephone
      three weeks after the questionnaire was mailed. RESULTS: A total of 345 patient
      satisfaction questionnaires (67%) were returned, and 47% of the cases completed
      the telephone interview. There was no difference in satisfaction between the
      women who received the guideline and those who did not. Most found the guideline
      easy to read (99%), and the majority (89%) felt that it clearly explained what
      happens if further tests are needed. However, a fourth thought the guideline made
      them anxious. CONCLUSION: A plain-language guideline was useful for most women
      who had abnormal screening results, although it did not alter the women's
      satisfaction with the MBSP. The guideline did increase anxiety for some women.
      These women may require other help to decrease their anxiety.

PMID- 12000103
TI  - Aron and Reed Ash are co-recipients of the 2001 Margaret Hay Edwards Achievement
      Medal.

PMID- 12000104
TI  - Problems associated with prostate cancer: differences of opinion among health
      care providers, patients, and spouses.
AB  - BACKGROUND: Problems accompany any experience with cancer. METHODS: Patients,
      spouses, and providers were asked to identify their perceptions of the problems
      associated with recently diagnosed prostate cancer. Their answers were compared
      across respondent categories (physician, nurse, patient, and spouse) and cross
      informant variance was analyzed. RESULTS: Significant variation in responses was
      noted by respondent categories in spite of the relatively small sample.
      CONCLUSION: The response variance may contribute to communication problems among
      patients, spouses, and providers, as well as missed opportunities for medically
      appropriate referrals to psychological treatment and community support resources.

PMID- 12000105
TI  - Rehabilitation after laryngectomy: a practical approach and guidelines for
      patients.
AB  - BACKGROUND: Laryngectomy causes irreversible loss or distortion in basic human
      habits, such as speech, swallowing, smelling, tasting, coughing and kissing.
      Rehabilitation can help a patient to reach the maximal potential within the
      context of his or her social milieu. Learning and adapting the lifestyle of
      living after laryngectomy is a challenge that faces the patient and the doctor.
      METHOD: The authors' Head and Neck Cancer Center treated more than 100 laryngeal
      carcinomas with laryngectomy during a five-year period. A multidisciplinary group
      was established for the education and rehabilitation of laryngectomized patients
      in order to provide them with the best possible overall quality of life. The
      group's rehabilitation program is described.

PMID- 12000106
TI  - The National DES Education Program: effectiveness of the California Health
      Provider Intervention.
AB  - BACKGROUND: Diethylstilbestrol (DES), a synthetic estrogen prescribed during
      pregnancy between 1938 and 1971, was later shown to have serious health effects,
      including higher risks of cancer in daughters and mothers. The authors report
      results of an intervention to increase health care providers' awareness of
      preventive care for women exposed to DES before birth. METHODS: A controlled
      trial enrolled 20 to 25 health care providers in each of three communities to
      test the effectiveness of an academic detailing intervention. Outcomes
      (knowledge, routine screening) were assessed by provider questionnaires and
      patient surveys. RESULTS: DES knowledge, familiarity with national guidelines,
      and screening for exposure increased significantly in the intervention
      communities but not in the control communities. The intervention effect for DES
      screening was significant (p = 0.01). Patient surveys confirmed provider self
      report. CONCLUSION: Academic detailing can increase DES knowledge and history
      taking among primary care providers. This intervention could be disseminated to
      increase knowledge of DES preventive care.

PMID- 12000107
TI  - Cancer education takes on a spiritual focus for the African American faith
      community.
AB  - BACKGROUND: The faith community, specifically African American (AA) churches, has
      been a partner in the delivery of health educational messages for the past two
      decades. METHODS: This article goes beyond the physical setting of the church to
      describe how and why spirituality is a particularly effective and essential
      component of one breast and cervical cancer education program, The Witness
      Project. Examining the theoretical and methodological foundations of this program
      demonstrates that the content as well as the messengers are strategically
      positioned within the AA faith community. CONCLUSION: This program is an example
      of cancer education's finding a culturally sanctioned method to become a part of
      a different kind of "ministry" within the AA faith community on a national level.

PMID- 12000108
TI  - Impact of culturally, linguistically, and literacy relevant cancer information
      among Hispanic farmworker women.
AB  - BACKGROUND: This pilot investigation describes the impact of culturally,
      linguistically, and literacy relevant cancer information in terms of knowledge,
      satisfaction, comfort level, and intentional and actual breast/cervical cancer
      screening practices among Hispanic migrant and seasonal farmworker women.
      METHODS; Study phases were: 1) formative research; 2) instrument development and
      pretesting; and 3) pilot evaluation among 65 women using a one-group pretest
      posttest design. RESULTS: Participants' reactions to the intervention were highly
      favorable. While an increase in knowledge (p < 0.001) was observed, no change in
      comfort was noted. Ninety-seven percent stated that they would be willing to miss
      a day of work (intent) to get a health check-up. CONCLUSION: Educational tools
      that are culturally, linguistically, and low-literacy can be promising
      interventions to promote awareness about breast and cervical cancer screening.

PMID- 12000109
TI  - Turkish people's knowledge of cancer and attitudes toward prevention and
      treatment.
AB  - BACKGROUND: The basic level of cancer knowledge of the population is as important
      in controlling cancer as diagnostic tools, screening, and new approaches to
      prevention, early diagnosis, and treatment. METHODS: A questionnaire consisting
      of 24 questions was given to 630 healthy Turkish people to determine their basic
      knowledge and attitudes regarding cancer. RESULTS: The majority of respondents
      (78%) were found to have little knowledge of cancer despite the fact that the
      average level of education of the sample was superior to that of the general
      population. Educational level was the major predictive factor influencing the
      basic knowledge and attitudes of the respondents. CONCLUSION: The overall
      education of the public as well as the basic level of knowledge of cancer must be
      improved in cooperation with oncology societies and media in order to overcome
      the cancer burden in Turkey.

PMID- 12000110
TI  - Prevalence of tobacco consumption in schoolchildren in rural India--an epidemic
      of tobaccogenic cancers looming ahead in the Third World.

PMID- 12000111
TI  - The effectiveness of an Internet-based tutorial in improving primary care
      physicians' skin cancer triage skills.
AB  - OBJECTIVE: To determine the efficacy of an Internet-based skin cancer triage
      intervention for physicians. METHODS: Physicians were randomly assigned to an
      intervention group or a control group. The 14 outcome measures included diagnosis
      and evaluation planning for malignant melanoma, basal cell carcinoma, and
      squamous cell carcinoma. RESULTS: Forty-six physicians (27 of 39 in the
      intervention group) completed the program. The intervention group scored
      significantly higher than did the control group in nine of 14 outcome measures;
      this improvement was maintained for five of the nine outcomes. CONCLUSION: The
      Internet intervention improved physicians' skin cancer diagnosis and evaluation
      planning test performances.

PMID- 12000112
TI  - PET imaging of ischemic neuronal death in the hippocampus of living monkeys.
AB  - The aim of the present study was to visualize postischemic hippocampal neuronal
      death in the living monkey brain, using a high-resolution positron emission
      tomography (PET) and novel radioligands. In preceding papers, we reported on
      postischemic hippocampal neuronal death in a model of Japanese monkeys (Macaca
      fuscata) undergoing a 20-min complete whole-brain ischemia. Using the same model
      here, we investigated the in vivo bindings of two radiotracers, [11C]Ro15-4513 (a
      type II benzodiazepine receptor ligand) and [11C](+)3-MPB (a muscarinic
      cholinergic receptor ligand), in the hippocampus on day 7 after ischemia, as
      compared to the normal hippocampus. A significant decrease in the in vivo binding
      of [11C]Ro154513 and [11C(+)3-MPB was observed in the postischemic monkey
      hippocampus on day 7 after ischemia compared to controls. Light and electron
      microscopic analyses of postischemic CA1 neurons showed typical features of
      coagulation necrosis, as associated with a marked reduction of postsynaptic
      densities and presynaptic vesicles. These results suggest that semiquantification
      of hippocampal neuronal death is possible in the living primate brain using PET,
      and that the same procedures can be applied for evaluating neuronal cell loss in
      patients with ischemic injuries and/or dementia.

PMID- 12000113
TI  - Mu opioid receptors are in discrete hippocampal interneuron subpopulations.
AB  - In the rat hippocampal formation, application of mu opioid receptor (MOR)
      agonists disinhibits principal cells, promoting excitation-dependent processes
      such as epileptogenesis and long-term potentiation. However, the precise location
      of MORs in particular inhibitory circuits, has not been determined, and the roles
      of MORs in endogenous functioning are unclear. To address these issues, the
      distribution of MOR-like immunoreactivity (-li) was examined in several
      populations of inhibitory hippocampal neurons in the CA1 region using light and
      electron microscopy. We found that MOR-li was present in many parvalbumin
      containing basket cells, but absent from cholecystokinin-labeled basket cells.
      MOR-li was also commonly in interneurons containing somatostatin-li or
      neuropeptide Y-li that resembled the "oriens-lacunosum-moleculare" (O-LM)
      interneurons innervating pyramidal cell distal dendrites. Finally, MOR-li was in
      some vasoactive intestinal peptide- or calretinin-containing profiles resembling
      interneurons that primarily innervate other interneurons. These findings indicate
      that MOR-containing neurons form a neurochemically and functionally heterogeneous
      subset of hippocampal GABAergic neurons. MORs are most frequently on interneurons
      that are specialized to inhibit pyramidal cells, and are on a limited number of
      interneurons that target other interneurons. Moreover, the distribution of MORs
      to different neuronal types in several laminae, some relatively far from
      endogenous opioids, suggests normal functional roles that are different from the
      actions seen with exogenous agonists such as morphine.

PMID- 12000114
TI  - Developmental expression of potassium-channel subunit Kv3.2 within subpopulations
      of mouse hippocampal inhibitory interneurons.
AB  - The developmental expression of the voltage-gated potassium channel subunit,
      Kv3.2, and its localization within specific mouse hippocampal inhibitory
      interneuron populations were determined using immunoblotting and
      immunohistochemical techniques. Using immunoblotting techniques, the Kv3.2
      protein was weakly detected at postnatal age day 7 (P7), and full expression was
      attained at P21 in tissue extracts from homogenized hippocampal preparations. A
      similar developmental profile was observed using immunohistochemical techniques
      in hippocampal tissue sections. Kv3.2 protein expression was clustered on the
      somata and proximal dendrites of presumed inhibitory interneurons. Using double
      immunofluorescence, Kv3.2 subunit expression was detected on subpopulations of
      GABAergic inhibitory interneurons. Kv3.2 was detected in approximately 100% of
      parvalbumin-positive interneurons, 86% of interneurons expressing nitric oxide
      synthase, and approximately 50% of somatostatin-immunoreactive cells. Kv3.2
      expression was absent from both calbindin- and calretinin-containing
      interneurons. Using immunoprecipitation, we further demonstrate that Kv3.2 and
      its related subunit Kv3.1b are coexpressed within the same protein complexes in
      the hippocampus. These data demonstrate that potassium channel subunit Kv3.2
      expression is developmentally regulated in a specific set of interneurons. The
      vast majority of these interneuron subpopulations possess a "fast-spiking"
      phenotype, consistent with a role for currents through Kv3.2 containing channels
      in determining action potential kinetics in these cells.

PMID- 12000115
TI  - Chronic food restriction is associated with subtle dendritic alterations in
      granule cells of the rat hippocampal formation.
AB  - The hippocampal formation undergoes significant morphological and functional
      changes after prolonged feeding with low-protein diets. In this study we tested
      whether prolonged food restriction causes deleterious alterations in this brain
      region as well. It was found that the total number of dentate granule cells and
      hippocampal CA3 and CA1 pyramidal neurons did not differ between controls and
      rats submitted to food restriction (40%) for 36 weeks. Likewise, no effects of
      this dietary regimen have been detected on the morphology of the dendritic trees
      of hippocampal pyramids, and on the total number of the mossy fiber-CA3 synapses.
      By contrast, the dendritic arborizations of granule cells were found to have a
      reduced number of segments in food-restricted rats. However, the spine density on
      the distal segments of their dendritic trees and the total number of axospinous
      synapses in the outer molecular layer of the dentate gyrus were increased in
      these animals. In addition, the total dendritic length of the granule cells and
      the overall surface area of the active zones of the synapses in the outer
      molecular layer were preserved, indicating that the capacity of dentate granule
      cells to process afferent stimuli is likely to be unaffected by this dietary
      treatment. Supporting this view are the results obtained in the water maze
      experiment which show that food-restricted rats exhibit unimpaired spatial
      abilities, which are known to be dependent on the entorhinal drive towards the
      hippocampal formation. These results show that, among hippocampal neurons,
      dentate granule cells are selectively vulnerable to food restriction.
      Nonetheless, the reorganization which takes place in their dendrites and synapses
      is capable of minimizing the functional impairments that were expected to occur
      following changes in the hippocampal neuronal circuitry induced by this type of
      dietary restriction.

PMID- 12000116
TI  - Melatonin receptors in rat hippocampus: molecular and functional investigations.
AB  - Since binding sites for melatonin have been found in the hippocampus of several
      mammals, it has been suggested that the pineal hormone melatonin is able to
      modulate neuronal functions of hippocampal cells. In order to get more insight
      into the role of melatonin for the functions of hippocampal cells, the following
      experiments were performed: male rats, maintained under a 12/12-h light-dark
      cycle, were sacrificed by decapitation at zeitgeber times (h) ZT2, ZT8, and ZT15
      (ZT0 = lights on); for experiment 1, gene expression for melatonin receptors was
      detected in the hippocampus and in hippocampal subfields by means of the RT-PCR
      technique; for experiment 2, electrophysiological and pharmacological properties
      of melatonin receptors heterologously expressed in Xenopus oocytes after
      injection of mRNA from the hippocampus were analyzed by means of voltage clamp
      technique; and for experiment 3, effects of melatonin on the spontaneous firing
      rate of action potentials in the CA1 regions of hippocampal slices were analyzed
      by means of extracellular recordings. The RT-PCR data revealed that transcripts
      for both the MT1 and MT2 melatonin receptors are present in the dentate gyrus,
      CA3, and CA1 regions, and the subiculum of the hippocampus. Injection of mRNA
      from rat hippocampus into the Xenopus oocytes led to the functional
      reconstitution of melatonin-sensitive receptors, which activates calcium
      dependent chloride inward currents. The melatonin responses were abolished by
      simultaneous administration of the antagonists 2-phenylmelatonin and luzindole,
      and were unaffected by the MT2 antagonist 4-phenyl-2-propionamidotetralin. Bath
      applied melatonin (1 micromol/l) enhances the firing rate of neurons in the CA1
      region. The effect was small in experiments performed at ZT8 (<2 times the
      initial level) and large in experiments performed at ZT15 (>6 times). The changes
      of neuronal firing rate induced by melatonin were completely suppressed with
      simultaneous administration of the melatonin receptor antagonist luzindole (10
      micromol/l). The results indicate that melatonin may play an important role in
      modulating neuronal excitability in the hippocampus.

PMID- 12000117
TI  - Early induction of secretoneurin expression following kainic acid administration
      at convulsant doses in the rat and gerbil hippocampus.
AB  - The expression of secretogranin-II and its major proteolytic product
      secretoneurin (SN) is under the control of neuronal excitation, as demonstrated
      by treating rats with the excitotoxic kainic acid (KA). Differences in the
      structure and function of the hippocampus in rats and gerbils have been
      described; these suggest possible differential reactive responses to KA. In the
      present study, the SN immunostaining pattern in relation with cell damage is
      analyzed from 6 h to 4 days following KA administration in rats and gerbils.
      Dramatic differences in the expression of SN were found in the hippocampal
      complex following KA administration in gerbils and rats. A robust increase in SN
      immunoreactivity was detected in the pyramidal cell layer of the rat hippocampus,
      especially in the CA1 area. In the gerbil, however, a strong increase in SN
      immunostaining was detected in interneurons of the hippocampal formation, as
      shown by double-labeling immunohistochemistry to SN and the calcium-binding
      proteins parvalbumin, calbindin, and calretinin. In addition, no damage (in the
      hippocampal formation) or moderate damage (in the entorhinal cortex) was observed
      in the gerbil, in contrast to the rat. The administration of KA and the GABA-B
      receptor inhibitors (CGP56999A or CGP36742) to the gerbil resulted in a strong
      rise in SN immunoreactitivty in the CA1 pyramidal cell layer of the hippocampus,
      as in the rat. However, no increased cell damage was observed under these
      conditions. The present data provide evidence of a species-differential reactive
      response to KA that might be based, in part, on distinct inhibitory
      intrahippocampal circuitry.

PMID- 12000118
TI  - Projections from the lateral, basal, and accessory basal nuclei of the amygdala
      to the entorhinal cortex in the macaque monkey.
AB  - We used the anterograde tracers Phaseolus vulgaris-leucoagglutinin (PHA-L) and
      biotinylated dextran amine (BDA) to examine the projections from the lateral,
      basal, and accessory basal nuclei of the amygdaloid complex to the entorhinal
      cortex in Macaca fascicularis monkeys. The heaviest amygdaloid projections
      originate in the lateral nucleus, which innervates the rostrally situated
      entorhinal fields but does not project to the caudal entorhinal cortex. The most
      extensive projections originate in the ventral division of the lateral nucleus.
      Injections in this subdivision lead to moderate to heavy fiber and terminal
      labeling in the entorhinal cortex, rostral levels of the rostral intermediate El
      (ER) and lateral fields, (ELr), and light labeling in the olfactory field EO. The
      projections from all portions of the lateral nucleus terminate most heavily in
      layer III. Layer II of EO and ER also receives a substantial input from the
      ventral division of the lateral nucleus. Layer II of ELr receives light
      innervation from all portions of the lateral nucleus that project to layer III.
      Projections from the basal nucleus arise mainly from the parvicellular division
      and are light to moderate in density. Fibers terminate predominantly in ELr, ER,
      EO, and the caudal portion of the lateral field (Elc); only the most rostral
      portion of El receives projections. While fibers from the basal nucleus innervate
      the same layers as the projections from the lateral nucleus, they tend to have a
      more vertical or radial orientation within the entorhinal cortex. Electron
      microscopic analysis of these fibers and terminals indicates that they
      overwhelmingly form asymmetrical synapses onto dendrites and dendritic spines.
      The accessory basal nucleus provides a light projection to the same regions of
      the entorhinal cortex innervated by the lateral and basal nuclei.

PMID- 12000119
TI  - Comparative analysis of cholinergic innervation in the dorsal hippocampus of
      adult mouse and rat: a quantitative immunocytochemical study.
AB  - To obtain quantitative data on the distribution of the acetylcholine (ACh)
      innervation in the dorsal hippocampus of adult mouse (C57/B6) and rat (Sprague
      Dawley), a semicomputerized method was used to measure the length of
      immunostained axons in hippocampal sections processed for light microscopic
      immunocytochemistry with a highly sensitive antibody against choline
      acetyltransferase (ChAT). The results could be expressed in density of axons
      (meters per mm3) for the different layers and regions of dorsal hippocampus (CA1,
      CA3, DG), and also in density of axon varicosities (millions per mm3), after
      having determined the average number of varicosities per unit length of ChAT
      immunostained axon (4 varicosities/10 microm). In mouse, the mean regional
      densities of ACh innervation were thus measured at 13.9, 16.1, and 15.8 m of
      axons, for 5.6, 6.4, and 6.3 million varicosities per mm3 of tissue, in CA1, CA3,
      and DG, respectively. The values were comparable in rat, except for CA1, in which
      the densities were lower than in mouse by 40% in the stratum lacunosum, and 20%
      in the stratum radiatum. Otherwise, the laminar patterns of innervation were
      similar in the two species, the highest densities being found in the stratum
      lacunosum moleculare of CA3, pyramidale of both CA1 and CA3, and moleculare of
      DG. These quantitative data will be of particular interest to evaluate changes in
      mutant mice, or mice and rats subjected to experimental conditions affecting the
      cholinergic phenotype.

PMID- 12000120
TI  - Quantitative and morphological analysis of dentate granule cells with recurrent
      basal dendrites from normal and epileptic rats.
AB  - Granule cells with recurrent basal dendrites (RBDs) were previously reported in
      both control and epileptic rats. RBDs are dendrites that arise from the basal
      half of granule cell bodies and curve toward and extend into the molecular layer.
      They are increased in frequency in the pilocarpine model of epilepsy. The present
      study was undertaken to analyze the distribution and morphology of granule cells
      with RBDs and the synaptic connections of RBDs. Granule cells were labeled by
      retrograde transport of biocytin. Those with an RBD were found throughout the
      granule cell layer, but were most numerous at the hilar border. The morphology of
      these cells varied in the different depths of the granule cell layer; the angle
      of their cell body's long axis was mainly vertical at the hilar margin, and
      changed to virtually horizontal close to the molecular layer border. Quantitative
      data on the distribution of granule cells with RBDs and the angle of the cell
      body's long axis confirmed these descriptions. At the electron microscopic level,
      RBDs showed the typical features of dendrites and formed numerous axodendritic
      and axospinous synapses with labeled and unlabeled axon terminals. These results
      showed that RBDs of granule cells from epileptic rats are postsynaptic to axon
      terminals, including mossy fibers, and thus are involved in a similar synaptic
      circuitry as apical dendrites of granule cells from these animals.

PMID- 12000121
TI  - Effects of chronic stress on hippocampal long-term potentiation.
AB  - Chronic stress causes atrophy of the apical dendrites of CA3 pyramidal neurons
      and deficits in spatial memory. We investigated the effects of chronic stress on
      hippocampal physiology and long-term potentiation (LTP) in the CA3 and dentate
      gyrus (DG). Rats were subjected to chronic (21 days, 6 h/day) restraint stress
      and tested for LTP 48 h following the last stress episode. Control animals were
      briefly handled each day, similar to the experimental group but without
      restraint. To eliminate acute stress effects, a second control group of rats was
      subjected to a single acute (6 h) restraint stress and tested for LTP 48 h later.
      Field potential recordings were made, under chloropent anesthesia, from the
      stratum lucidum of CA3, with stimulation of either the mossy fiber or
      commissural/associational pathways, or in the DG granule-cell layer, with
      stimulation of the medial perforant pathway. Chronic stress produced a
      suppression of LTP at 48 h compared to controls in a site-specific manner,
      namely, significantly lower LTP in the medial perforant input to the DG and also
      in the commissural/associational input to the CA3, but not in the mossy fiber
      input to CA3. The animals subjected to acute stress and tested 48 h later did not
      show a suppression in LTP. High-frequency stimulation (HFS) of the
      commissural/associational and mossy fiber inputs to CA3 produced epileptic
      afterdischarges in 56% of acutely stressed animals and in 29% of chronically
      stressed animals, whereas HFS caused afterdischarges in only 9% of nonstressed
      controls. No afterdischarges were seen in the medial perforant path input to DG.
      In order to explore the basis for these changes, we performed paired-pulse
      inhibition/facilitation (PPI/F) and current-source-density (CSD) analysis in
      stressed and control animals. For PPI/F, acute stress caused an overall
      significant enhancement of excitation in the commissural/associational input to
      CA3 and medial perforant path input to DG. In contrast, chronic stress did not
      produce significant changes in PPI/F. The CSD analysis revealed significant
      chronic stress-induced shifts in the current sources and sinks in the apical
      dendrites and pyramidal cell layers of the CA3 field but not in the DG. These
      results are consistent with the morphological findings for stress effects upon
      dendrites of CA3 neurons. Furthermore, they suggest that chronic stress produces
      changes in the input-output relationship in the hippocampal trisynaptic circuit
      which could affect information flow through this structure.

PMID- 12000122
TI  - Hyperexcitability and epilepsy associated with disruption of the mouse neuronal
      specific K-Cl cotransporter gene.
AB  - Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is
      exclusively expressed in neurons where it is thought to drive intracellular Cl-
      to low concentrations and shift the reversal potential for Cl- conductances such
      as GABA(A) or glycine receptor channels, thus participating in the postnatal
      development of inhibitory mechanisms in the brain. Indeed, expression of the
      cotransporter is low at birth and increases postnatally, at a time when the
      intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid
      switches its effect from excitatory to inhibitory. To assert the significance of
      KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal
      specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2
      exhibit frequent generalized seizures and die shortly after birth. We also show
      upregulation of Fos, the product of the immediate early gene c-fos, and the
      significant loss of parvalbumin-positive interneurons, both indicative of brain
      injury. The regions most affected are the hippocampus and temporal and entorhinal
      cortices. Extracellular field potential measurements in the CA1 hippocampus
      exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A)
      receptor, further increased hyperexcitability in homozygous hippocampal sections.
      Pharmacological treatment of pups showed that diazepam relieved the seizures
      while phenytoin prevented them between postnatal ages P4-P12. Finally, we
      demonstrate that adult heterozygote animals show increased susceptibility for
      epileptic seizure and increased resistance to the anticonvulsant effect of
      propofol. Taken together, these results indicate that KCC2 plays an important
      role in controlling CNS excitability during both postnatal development and adult
      life.

PMID- 12000123
TI  - Learning deficits in aged rats related to decrease in extracellular volume and
      loss of diffusion anisotropy in hippocampus.
AB  - The extracellular space (ECS) is the microenvironment of the nerve cells and an
      important communication channel, allowing for long-distance extrasynaptic
      communication between cells. Changes in ECS size, geometry, and composition have
      been reported in diverse (patho)physiological states, including aging. In the
      present study, real-time tetramethylammonium (TMA+) iontophoresis was used to
      quantify ECS diffusion parameters in different brain regions of adult and
      behaviorally characterized aged rats. Prior to ECS diffusion measurement,
      superior and inferior learners were selected from a large group of aged rats,
      according to their performance in the open-field water maze. The main finding was
      that the degree of impaired maze performance of old rats correlates, firstly,
      with decrease in ECS volume, loss of diffusion anisotropy in hippocampus, and
      degree of astrogliosis, and secondly, with disorganization of the astrocytic
      processes and reduction of hippocampal ECS matrix molecules. Importantly, no
      significant differences were found in the density of neurons in any region of the
      hippocampus or dentate gyrus. The alterations in hippocampal diffusion parameters
      evident in aged animals with severe learning deficits could account for the
      learning impairment, due to their effects on extrasynaptic volume transmission
      and/or on the "cross-talk" between synapses, which has been suggested to be
      involved in neural processes associated with learning and memory formation.

PMID- 12000124
TI  - Post-training reversible inactivation of hippocampus reveals interference between
      memory systems.
AB  - A post-training reversible lesion technique was used to examine the effects of
      neural inactivation of the dorsal hippocampus on place and response learning.
      Male Long-Evans rats trained in one of two versions of a water plus-maze task
      received post-training intra-hippocampal infusions of the local anesthetic drug
      bupivacaine (0.75% solution, 0.5 microl), or saline. Post-training intra
      hippocampal infusions of bupivacaine attenuated acquisition of the place task and
      enhanced acquisition of the response task. Delayed (2-h) post-training infusions
      of bupivacaine did not affect retention in either task. The findings demonstrate
      (1) enhanced learning after reversible hippocampal lesions that is independent of
      treatment influences on non-mnemonic factors, and (2) inactivation of the dorsal
      hippocampus during the post-training memory consolidation period is sufficient to
      enhance response learning.

PMID- 12000125
TI  - Individual differences in spatial memory among aged rats are related to
      hippocampal PKCgamma immunoreactivity.
AB  - We reported previously that the extent of spatial memory impairment among aged
      rats was correlated positively with levels of protein kinase Cgamma in
      hippocampal homogenates measured by quantitative Western blotting (Colombo et
      al., 1997). In the current study, immunocytochemistry was used to test whether
      the relationship between elevated PKC-gamma and memory impairment among aged rats
      could be localized further within regions of the hippocampus. Six- and 24-month
      old male Long-Evans rats were first trained in the water maze on a standard place
      learning task and then trained 2 weeks later on a transfer task designed for
      rapid acquisition. In comparison with young rats, aged rats with impaired spatial
      memory had increased PKCgamma-immunoreactivity (PKCgamma-ir) in CA1 of the
      hippocampus, but not the dentate gyrus. In addition, PKCgamma-ir in CA1 was
      correlated positively with spatial memory impairment among aged rats on the
      standard place-learning and the transfer training tasks. The current results are
      consistent with our previous report of PKCgamma in hippocampal homogenates, and
      show further that the relationships between PKCgamma-ir and memory impairments
      among aged rats are most evident in area CA1. Thus age-related impairments of
      spatial memory, as well as deficits in the flexible use of previously acquired
      information, may result from dysregulation of PKCgamma.

PMID- 12000126
TI  - A research on the microfungal flora of some greenhouse soils in the vicinity of
      Lapseki Canakkale, Turkey.
AB  - Qualitative and quantitative distributions of microfungal flora of the some
      greenhouse soils in the vicinity of Lapseki, Canakkale were studied. A total of
      25 soil samples were collected from 10 cm depth in five greenhouses. Using soil
      dilution technique, 128 different microfungal isolates were obtained Isolates
      collected belonged to Oomycetes (1), Zygomycetes (7), Ascomycetes (9) and 96
      belonging to the Deuteromycetes Fifteen isolates were classified as Mycelia
      Sterilia. The genera of microfungi most abundant in the greenhouse soils were
      Aspergillus, Penicillium, Geomyces, Exophiala and Fusarium. Qualitative and
      quantitative distributions of the Aspergillus were higher than those of the other
      genera. It was found that the maximum value was in greenhouse 5 and the minimum
      value was in greenhouse 4. The solarization method was the most effective in
      reducing fungal numbers.

PMID- 12000127
TI  - Lymphadenitis, trans-epidermal elimination and unusual histopathology in human
      rhinosporidiosis.
AB  - From a study of rhinosporidial tissues of 64 human cases of ocular, urethral and
      nasopharyngeal disease, unusual histopathological features of 27 cases are
      described. Histopathological evidence of lymphadenitis in rhinosporidiosis is
      presented for the first time. The phenomenon of 'trans-epidermal elimination' of
      sporangia of the causative pathogen Rhinosporidium seeberi is illustrated and it
      is argued that this phenomenon is rather the pathogen's mechanism for endospore
      dispersal than a non-specific defence reaction of the host as has previously been
      suggested. Other unusual appearances described include variations in the
      intensity and composition of the host-cell infiltrate in tissues from different
      patients and in different portions of the same tissue, pitfalls in
      histopathological diagnosis, and unusual appearances of the pathogen.
      Histopathological clues to the pathogenesis of rhinosporidiosis and mechanisms of
      anti-rhinosporidial immunity in the host are discussed, illustrating the probable
      occurrence of immunesuppressive reactions to account for the variations in the
      density and composition of the host-cell infiltrate and the state of the
      rhinosporidial sporangia--intact or degenerate--, relating these variations to
      the chronicity, recurrences and systemic dissemination of rhinosporidiosis.

PMID- 12000128
TI  - The importance of microscopic examination in the management of desquamative
      diseases of the scalp.
AB  - After determining the usual malassezic biota of the scalp in adult, normal
      persons, 259 patients with different desquamative diseases were studied by a
      simple adhesive tape technique. The main purpose of this study was to investigate
      the utility of this technique to improve the diagnosis and treatment of patients.
      Most patients with seborrhoeic dermatitis and sebopsoriasis demonstrated large
      numbers of Malassezia spp. cells corresponding to the so called "pityrosporosis".
      Only 43.6% of patients with pityriasis capitis (dandruff) presented with such a
      diagnosis. Symptomatic pityrosporosis of the scalp should be treated with
      imidazolic derivatives or other antifungal substances. Patients with psoriasis of
      the scalp showed a typical microscopic picture represented by parakeratosic
      (nucleated) keratinocytes with absence of lipophilic yeasts which should be
      attributed to the usual dryness of the scales Microbial epidermitis (eczema) of
      the scalp revealed another characteristic picture constituted by abundant
      leukocytes and bacteria without the presence of yeasts. The different microscopic
      pictures seen with this simple technique for diseases of the scalp, offer an
      adjunct to make a proper diagnosis and to establish a convenient treatment in
      cases which are not clinically well defined.

PMID- 12000129
TI  - Host resistance against Candida alibcans infection in mice with adjuvant induced
      arthritis.
AB  - In mice and humans two distinct CD4+ helper T cells, known as Th1 and Th2 are
      identified. They are characterized by the different cytokine milleau they induce.
      The balance between Th1 and Th2 responses is thought to be decisive for the
      initiation and course of some autoimmune disorders, as well as for the outcome of
      infectious processes. In the present study the development of Candida alibcans
      infection in mice with adjuvant-induced arthritis was investigated. An impaired
      host resistance against C. alibcans in arthritic mice was registered when the
      inoculation was done during the early and the established phases of arthritis. In
      contrast, the slight elevation of the number of survivors was detected when the
      infection was induced at the peak of inflammation. These data correlated with the
      changes of serum TNF-alpha level and delayed type hypersensitivity (DTH) to C.
      alibcans.

PMID- 12000130
TI  - Sporothrix schenckii isolated from domestic cats with and without sporotrichosis
      in Rio de Janeiro, Brazil.
AB  - A total of 148 cats with a clinical and mycologic diagnosis of sporotrichosis and
      84 apparently healthy cats with domiciliary contact with the affected animals
      were studied. Sporothrix schenckii was isolated from 148 (n = 148; 100%) clinical
      samples of cutaneous lesion (biopsy, swab or aspiration of purulent secretion),
      47 (n = 71; 66.2%) nasal cavities, 33 (n = 79; 41.8%) oral cavities, and 15 (n =
      38; 39.5%) nails of cats with sporotrichosis. Histopathological examination
      revealed yeast-like structures in 50 (n = 70; 71.4%) of the biopsies studied. S.
      schenckii was isolated from the blood culture of one cat (n = 5, 20%) with the
      disseminated cutaneous form of the disease. On another occasion, the fungus was
      isolated from the testis of one (n = 7; 14.3%) of the animals submitted to
      sterilization. In the group of cats with domiciliary contacts, 3 (n = 84; 3.57%)
      oral swabs showed positive cultures. Isolation of S. schenckii from different
      clinical specimens during both the clinical and preclinical phase reinforces the
      zoonotic potential of feline sporotrichosis.

PMID- 12000131
TI  - Occurrence of keratinophilic fungi and dermatophytes on domestic birds in
      Nigeria.
AB  - Feathers, nails and beaks of one hundred and twenty common birds in Nigeria,
      Chicken [50], Ducks [20], Turkeys [15] and Pigeons [35], were examined using the
      soil plate technique for their mycoflora. 15 species of fungi were recovered and
      they belong to the genera Chrysosporium, Trichophyton, Microsporum, Aspergillus,
      Fusarium, Mucor Rhizopus, Penicillium and Trichoderma. Microsporum gypseum was
      the species most frequently isolated (35% of the samples). The most common genus
      was Chrysosporium and C. keratinophilum was the species with the highest
      frequency in the genus (28.3%). The species isolated included potential pathogens
      and mycotoxin producing fungi (Aspergillus flavus, A. niger, Fusarium oxysporum).

PMID- 12000132
TI  - Deoxynivalenol-nonproducing fusarium graminearum causes initial infection, but
      does not cause disease spread in wheat spikes.
AB  - Fusarium graminearum is a major pathogen that causes fusarium head blight (FHB)
      in wheat and produces deoxynivalenol (DON) in infected grain. In previous
      studies, the trichodiene synthase gene (Tri5) in the fungal strain GZ3639 was
      disrupted to produce the DON-nonproducing strain GZT40. In this report, the
      virulence of strains GZ3639 and GZT40 was tested on wheat cultivars with various
      resistance levels by using methods of spray inoculation and injection inoculation
      with fungal conidia. Under field and greenhouse conditions, strain GZ3639
      produced significantly more disease symptoms and reduced more yield than strain
      GZT40 in all wheat cultivars tested. Conidia of strain GZT40 germinated and
      infected inoculated spikelets, but disease symptoms were limited to inoculated
      spikelets without spread to uninoculated spikelets. When strain GZT40 was
      inoculated using the spray method, multiple initial infection sites in a spike
      resulted in higher levels of disease symptoms than in spikes inoculated by a
      single injection. Greenhouse tests confirmed that strain GZT40 did not produce
      DON in the infected kernels following either inoculation method. The results
      confirm that DON production plays a significant role in the spread of FHB within
      a spike, and are the first report that DON production is not necessary for
      initial infection by the fungus.

PMID- 12000133
TI  - Rediscovery of Claviceps sorghi (Ascomycotina: Clavicipitaceae) in India.
AB  - During last twenty years, endemic Claviceps sorghi was largely replaced in India
      by an introduced species Claviceps africana. Recently, C. sorghi was found and
      isolated from Sorghum bicolor (Gulbarga, Karnataka). Macroconidia were smaller
      than in the type description, 7.6-14.5 (avg. 11.4) x 3.8-6.1 (avg. 4.8) microm;
      microconidia were rounded to oval, 2.5-3 microm in diameter. When plated, only
      the macroconidia underwent secondary conidiation. Sporulation was maintained only
      in cultures grown on sucrose-asparagine medium T2. Mycelium was reduced to sparse
      hyphae with numerous short conidiophores soon obscured by yeastlike conidial
      mass. RAPD patterns of isolates GUL, MH74 (Maharashtra), NAP7 and NAP5 (Andhra
      Pradesh) with 6 primers were almost identical and distinct from those of C.
      africana. Sequence of rDNA containing ITS1-5.8S-ITS2 region for isolate GUL
      (AJ306621) corresponded to that of the authentic material of C. sorghi (AJ242869)
      confirming thus the presence of C. sorghi in Central India.

PMID- 12000134
TI  - Ecto-5'-nucleotidase in B-cell chronic lymphocytic leukemia.
AB  - Literature on the behaviour of ecto-5'-nucleotidase in the course of B-cell
      chronic lymphocytic leukemia is briefly reviewed and aims for further researches
      are highlighted.

PMID- 12000135
TI  - Cytokines and depression: an analogic approach.
AB  - A growing body of evidence suggests that major depressive disorders may be
      accompanied by immune dysfunction and more particularly by an enhanced production
      of pro-inflammatory cytokines. The possible involvement of cytokines in
      depressive illness are based upon an analogic model. Pro-inflammatory cytokines
      are known to induce behavioral effects, and neuro-endocrine and immune activation
      similar to those observed in depression; these can be alleviated by
      antidepressant treatment. In this paper, we review research literature on the
      links between depressive illness and cytokine production and address further
      questions on this cytokine pathway. Further research is needed to see whether
      cytokines sustain specific depressive syndromes or whether cytokines induce
      depressive-like symptoms.

PMID- 12000136
TI  - Diet, constitutional and drug estrogens: common and pleiomorphic receptors.

PMID- 12000137
TI  - Steroid receptors in human breast tumorigenesis and breast cancer progression.
AB  - Steroid hormones, in particular estrogen and progesterone, play important roles
      in normal and neoplastic breast development. Alterations in both estrogen
      signaling and progesterone signaling likely occur during breast tumorigenesis and
      breast cancer progression. This is demonstrated by alteration of estrogen (ER)
      and progesterone (PR) receptor isoform expression as well as other factors such
      as coregulators, that can affect the activity, directly or indirectly, of in
      particular ER signal transduction pathways during breast tumorigenesis and breast
      cancer progression. A commonly emerging theme is the marked alteration of
      estrogen action that occurs during these processes. Since targeting ER signaling
      previously was successful, a better knowledge of all the molecular players
      involved in regulating estrogen signaling pathways and identifying changes that
      occur in vivo, seems critical to further exploit this previously successful
      approach and identify new targets for prevention and treatment of human breast
      cancer.

PMID- 12000138
TI  - Androgen-selective gene regulation in the prostate.
AB  - Androgens are essential for normal prostate growth and function but are also
      intimately associated with prostate cancer, an important cause of mortality in
      the ageing male population. The effects of androgens are mediated via a specific
      androgen receptor (AR) belonging to the nuclear receptor family and acting as a
      ligand-dependent transcription factor. The AR is built in a modular fashion and
      composed of a long N-terminal region with transactivation functions, a central
      DNA-binding domain, an intermediate hinge region and a C-terminal ligand-binding
      domain with additional transactivation functions. In its inactive form, the AR is
      complexed to heat-shock proteins, and mainly cytoplasmic. Following activation,
      the AR enters the nucleus, binds to its cognate DNA response elements as a
      homodimer and stimulates gene transcription. Various cofactors directly interact
      with the AR to modulate gene transcription. In addition, cross-talk between the
      AR and other signalling pathways has been proven for several prostate-expressed
      genes. Understanding the intricate networks underlying androgen-selective gene
      regulation represents a formidable challenge but might also offer the chance to
      identify new drug targets for the treatment of prostate carcinoma.

PMID- 12000139
TI  - Resveratrol and cancer: a review.
AB  - The various properties of the stilbene phytoalexin Resveratrol provide
      interesting new avenues of research in the field of chemoprevention and
      chemotherapy. A particular emphasis is given on xenobiotic-related
      carcinogenesis.

PMID- 12000140
TI  - Breast complaints and risk of breast cancer. Population-based study of 2,879 self
      selected women and long-term follow-up.
AB  - The aim of this study was to provide information about risk of breast cancer (BC)
      in women with breast complaints undergoing spontaneously clinical examination.
      The records of 2,879 self-selected symptomatic new patients observed
      consecutively were reviewed, and the chief breast complaint such as pain, lump
      and nipple discharge had been recorded. Patients were divided in three groups:
      Group A, 1,186 (41.2%) patients aged < 41 years; Group B, 809 (28.1%) patients
      aged 41-55 years; and Group C, 884 (30.7%) patients aged > 55 years. Pain was
      most common (P < 0.01) in Group A (60.8%), and lump in Groups B (53.3%) and C
      (89.7%). A total of 318 (11.0%) women had histologically confirmed BC (Group A =
      3.5%, Group B = 30.5%, Group C = 66.0%), accounting for 3.2, 16.4 and 12.0% of
      patients with pain, lump and nipple discharge, respectively. Breast complaints
      were equally (P= NS) distributed between patients with and without BC. The
      relative risk (RR) of BC developing ranged between 0.5-1.4, 0.5-1.9, and 0.6-3.0
      in Groups A, B, and C, respectively. It ranged between 0.3 and 0.7 in patients
      with breast pain, and was significantly higher (RR = 1.9-3.0) only in patients
      with breast lump aged > 40 years. In conclusion, in symptomatic patients BC risk
      is strictly related to age, and independent of the referred symptoms. Therefore,
      further investigations have to be warranted only when risk factors different from
      breast complaints are present.

PMID- 12000141
TI  - Inhibition of growth of human breast cancer cells in culture by neutron capture
      using liposomes containing 10B.
AB  - Cell destruction in boron neutron capture therapy is effected by nuclear reaction
      between 10B and thermal neutrons with the release of alpha-particles (4He) and
      lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He
      generation, therefore it is theoretically possible to destroy tumour cells
      without affecting adjacent healthy tissue, given selective delivery of compounds
      containing 10B. Liposomes wore prepared by vortex dispersion of solutions
      containing 10B compounds with dried lipid films and the effects of those
      compounds on human breast cancer cells in culture were examined after thermal
      neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B
      containing liposomes showed 40% suppression compared with liposomes without 10B,
      at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with
      liposomes prepared with 100 mm 10B-compound was as significant as with those made
      with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4
      microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line
      of breast cancer cells in culture to effect cytotoxicity and suppression of
      growth after thermal neutron irradiation.

PMID- 12000142
TI  - Miranda, a protein involved in neuroblast asymmetric division, is associated with
      embryonic centrosomes of Drosophila melanogaster.
AB  - Miranda, a highly coiled-coil protein, has been shown to be one of the key
      components necessary for the differential segregation of fate-determining factors
      during neurogenesis in Drosophila embryos. The multidomain protein Miranda, by
      segregating the transcription factor Prospero, guarantees the generation of cell
      diversity during the formation of the embryonic nervous system. While looking for
      new molecular components of the centrosome in Drosophila embryos, we have
      isolated a short isoform of Miranda. An antibody was raised directed against the
      central coiled-coil region of Miranda. and the pattern of expression of the
      protein was studied in details throughout Drosophila development. Here, we show
      that Miranda has a broad pattern of expression and is a rather ubiquitous
      molecule. Immunofluorescence on syncytial Drosophila embryos shows that Miranda
      has a dynamic redistribution and is associated with centrosomes. Electron
      microscopy on purified syncytial centrosomes shows that Miranda is located on the
      pericentriolar material along with gamma-tubulin. Taken all together, our data
      indicate for the first time that Miranda belongs to a growing class of proteins
      that concentrate at the centrosome in a cell-cycle and stage-specific manner. The
      observations that Miranda has a broad range of expression, as well as a dynamic
      and cell-cycle dependent subcellular localization, suggest that it may have
      alternative functions outside the embryonic nervous system. These potential new
      functions are discussed in this paper.

PMID- 12000143
TI  - Expression of peroxisome proliferator-activated receptors alpha and gamma in
      differentiating human colon carcinoma Caco-2 cells.
AB  - The expression of peroxisome proliferator-activated receptors alpha (PPARalpha)
      and gamma (PPARgamma) was studied in the human adenocarcinoma Caco-2 cells
      induced to differentiate by long term culture (15 days). The differentiation of
      Caco-2 cells was attested by increases in the activities of sucrase-isomaltase
      and alkaline phosphatase (two brush border enzymes), fatty acyl-CoA oxidase (AOX)
      and catalase (two peroxisomal enzymes), by an elevation in the protein levels of
      villin (a brush border molecular marker), AOX, peroxisomal bifunctional enzyme
      (PBE), catalase and peroxisomal membrane protein of 70 kDa (PMP70). and by the
      appearance of peroxisomes. The expression of PPARalpha and PPARgamma was
      investigated by Western blotting, immunocytochemistry, Northern blotting and S1
      nuclease protection assay during the differentiation of Caco-2 cells. The protein
      levels of PPARalpha, PPARgamma, and PPARgamma2 increased gradually during the
      time-course of Caco-2 cell differentiation. Immunocytochemistry revealed that
      PPARalpha and gamma were localized in cell nuclei. The PPARgamma1 protein was
      encoded by PPARgamma3 mRNA because no signal was obtained for PPARgamma1 mRNA
      using a specific probe in S1 nuclease protection assay. The amount of PPARgamma3
      mRNA increased concomitantly to the resulting PPARgamma1 protein. On the other
      hand, the mRNA of PPARalpha and PPARgamma2 were not significantly changed,
      suggesting that the increase in their respective protein was due to an elevation
      of the translational rate. The role played by the PPAR subtypes in Caco-2 cell
      differentiation is discussed.

PMID- 12000144
TI  - New magnet-sensitive structures in bacterial and archaeal cells.
AB  - The objects of the investigation were: distribution of intracellular magnet
      sensitive structures among different taxonomic groups of prokaryotes,
      localisation and organisation of the magnet-sensitive inclusions (MsI) in cells.
      The MsI were discovered in representatives of both prokaryotic domains (Bacteria
      and Archaea), 2 kingdoms and 7 orders of bacteria. They were some amorphous or
      non-crystalline globules with the electron-transparent centre surrounded with an
      electron-dense homogenous matrix. The magnetic nature of the structures was shown
      by attraction with an applied magnet both for the cell suspensions and for the
      MsI isolated and separated from the destroyed cells. The MsI were studied with
      transparent electron microscopy and with X-ray analyses. When the cells were
      grown in the iron-containing nutrient medium, the matrix was enriched with iron.
      It was shown also that some bacteria grown with cobalt or with chromium contained
      the cobalt- or chromium-enriched magnetic inclusions.

PMID- 12000145
TI  - Chemosensitivity of human prostate cancer cells PC3 and LNCaP to genistein
      isoflavone and beta-lapachone.
AB  - A wide spectrum of anti-cancer activity of genistein and beta-lapachone in
      various tumors has been reported in single treatments. In this study the combined
      effects of genistein and beta-lapachone on the chemosensitivity of LNCaP and PC3
      human prostate cancer cells was determined in vitro, using 3-[4,5-dimethylthiazol
      2-yl]-2-,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) to
      study treatment-induced growth inhibition and cytotoxicity and, annexin V
      fluoresceine (FI) and terminal deoxyribonucleotidyl transferase-mediated dUTP
      nick-end labeling (TUNEL)-propidium iodide (PI) assays to determine potential
      treatment-induced apoptosis and/or necrosis. The results showed: i) that both PC3
      and LNCaP are sensitive to single and combination treatments regardless of
      hormone sensitivity status, ii) that treatment induced dual death pathways
      (apoptosis and necrosis) in both cell types, iii) that growth inhibition in both
      cell types correlated positively with cell death via apoptosis at lower drug
      concentrations and necrosis at higher concentrations, iv) that combination of
      genistein and beta-lapachone had synergistic inhibitory effects on growth and
      proliferation in both cell types. The synergistic inhibitory effect was
      correlated positively with treatment-induced cell death via apoptosis and
      necrosis. The overall results indicate that combination treatments with beta
      lapachone and genistein are more potent in killing both PC3 and LNCaP cancer
      cells than treatment with either genistein or beta-lapachone alone. beta
      lapachone acts at the G1 and S phase checkpoints in the cell cycle, while
      genistein induces cell cycle arrest at the G2-M stage. The current results are
      therefore in agreement with the hypothesis that drug combinations that target
      cell cycles at different critical checkpoints would be more effective in causing
      cell death. This result provides a rationale for in vivo studies to determine
      whether beta-lapachone-genistein combination will provide effective chemotherapy
      for prostate cancer, regardless of the tumor sensitivity to hormone.

PMID- 12000146
TI  - Specific enhancement of acylase I and acylpeptide hydrolase activities by the
      corresponding N-acetylated substrates in primary rat hepatocyte cultures.
AB  - The specific effects of N-acetyl-L-methionine on acylase I activity and of both N
      acetyl-L-alanyl-L-alanine and N-acetyl-L-methionyl-L-alanine on N-acylpeptide
      hydrolase activity were investigated in primary rat hepatocyte cultures. Each of
      the above two substrates is known to be much more rapidly hydrolyzed than other
      derivatives of the same type under optimum enzyme assay conditions. After a two
      day incubation of the substrates in the presence of primary rat hepatocyte
      cultures, the N-acetylaminoacid was found to specifically induce an increase in
      the acylase I activity, whereas the two N-acetylated peptides increased the
      acylpeptide hydrolase activity in the soluble 100,000 x g fraction from the
      culture medium. No change in any of the enzyme activities could be detected
      during the same period of time when the medium was not supplemented with N
      acetylated substrates. In addition, the acylase I activity showed a dose
      dependent response when the N-acetyl-L-methionine concentration increased from 10
      fold to 50 fold. It is therefore suggested that the efficient hydrolysis of each
      type of substrate that occured in the 48 h hepatocyte cell cultures was due to
      the increase observed in the overall activity of the corresponding enzymes. The
      ratio of acylpeptide hydrolase to that of acylase I increased considerably when
      the medium was supplemented with N-acetylpeptides, and decreased in the presence
      of the N-acetylaminoacid.

PMID- 12000147
TI  - Topological analysis of chaos in a three-variable biochemical model.
AB  - A three-variable biochemical prototype involving two enzymes with autocatalytic
      regulation proposed by Decroly and Goldbeter (1987) is analyzed using a
      topological approach. A two-branched manifold, a so-called template, is thus
      identified. For certain control parameter values, this template is a horseshoe
      template with a global torsion of two half-turns. This implies that the
      bifurcation diagram can be described using the usual sequences associated with a
      unimodal map with a differentiable maximum as well as exemplified by the logistic
      map. Moreover, a type-I intermittency associated with a saddle-node bifurcation
      is exhibited. The dynamics from a single time series are also investigated to
      determine whether it is possible to investigate the dynamics of this biochemical
      model from the measure of a single concentration.

PMID- 12000148
TI  - Linear discrete population models with two time scales in fast changing
      environments II: non-autonomous case.
AB  - As the result of the complexity inherent in nature, mathematical models employed
      in ecology are often governed by a large number of variables. For instance, in
      the study of population dynamics we often deal with models for structured
      populations in which individuals are classified regarding their age, size,
      activity or location, and this structuring of the population leads to high
      dimensional systems. In many instances, the dynamics of the system is controlled
      by processes whose time scales are very different from each other. Aggregation
      techniques take advantage of this situation to build a low dimensional reduced
      system from which behavior we can approximate the dynamics of the complex
      original system. In this work we extend aggregation techniques to the case of
      time dependent discrete population models with two time scales where both the
      fast and the slow processes are allowed to change at their own characteristic
      time scale, generalizing the results of previous studies. We propose a non
      autonomous model with two time scales, construct an aggregated model and give
      relationships between the variables governing the original and the reduced
      systems. We also explore how the properties of strong and weak ergodicity,
      regarding the capacity of the system to forget initial conditions, of the
      original system can be studied in terms of the reduced system.

PMID- 12000149
TI  - A dynamic model of hypothermia as an adaptive response by small birds to winter
      conditions.
AB  - We present a dynamic programming model which is used to investigate hypothermia
      as an adaptive response by small passerine birds in winter. The model predicts
      that there is a threshold function of reserves during the night, below which it
      is optimal to enter hypothermia, and above which it is optimal to rest. This
      threshold function decreases during the night, with a particularly sharp drop at
      the end of the night, representing the time and energy costs associated with
      returning to normal body temperature. The results of the model emphasise the
      trade-off between energy and predation, not just between foraging options, but
      also between foraging during the day and entering hypothermia at night. The value
      of being able to use hypothermia represents not just energy savings, but also
      reduced predation risk due to changes in the optimal foraging strategy.
      Conditions which give a high value of hypothermia are short photoperiod, variable
      food supply, low temperatures, poor and scarce food supplies.

PMID- 12000150
TI  - Towards a quantification of ecological theory: the importance of multivariate
      analysis and of an accurate diversity measurement.

PMID- 12000151
TI  - On the information-theoretical meaning of Hill's parametric evenness.
AB  - The degree to which abundances are divided equitably among community species or
      evenness is a basic property of any biological community. Several evenness
      indices have been proposed to summarize community structure. However, despite
      their potential applicability in ecological research, none seems to be generally
      preferred. In this paper we show that, unlike other evenness indices without any
      clear information-theoretical meaning, Hill's parametric diversity measure
      E(alpha,0) has an immediate relation to Renyi's generalized information.
      Therefore, E(alpha,0) might be adequate for summarizing community structure
      within the context of a general theoretical framework of diversity analysis based
      on information theory.

PMID- 12000152
TI  - Reconstructive surgery for congenitally malformed mitral valve.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aims were to evaluate early and mid
      term survival and freedom from reoperation in patients with isolated mitral valve
      (MV) congenital malformation (MVCM) or in association with other cardiac defects,
      and to identify predictors for poor early and late outcome. METHODS: Between
      January 1990 and February 2001, 58 children with MVCM underwent MV-conserving
      surgery; patients were allocated to group I (n = 21) with isolated MVCM, and
      group II (n = 37) with MVCM and associated congenital heart defects (ACHD). MV
      stenosis was identified in 10 (48%) group I patients, and 11 (30%) group II
      patients (p = NS); MV insufficiency was present in 11 (52%) patients in group I,
      and in 26 (70%) of group II (p = NS). The most frequently found MVCM were annular
      dilatation (n = 13) cases and elongated chordae (n = 14). Hammock MV was found in
      nine patients (15%). RESULTS: Six (10%) hospital deaths occurred. Mortality was
      5% (n = 1) in group I, and 13% (n = 5) in group II (p = 0.4). Mean repair
      techniques per patient was 2.05+/-0.4 and 2.3+/-0.3 in groups I and II
      respectively (p = 0.009). Mechanical ventilation time was 2.1+/-1 and 2.8+/-0.7
      days in groups I and II (p = 0.003). The incidence of postoperative mitral
      regurgitation grade > or =1 was significantly higher in group II (p = 0.008). At
      five-year follow up, actuarial survival was 91.5% in group I and 86% in group II
      (p = 0.037). Actuarial reoperation-free survival was 85% in group I and 73% in
      group II (p = 0.01). Multivariate analysis showed age >12 months (p = 0.033),
      hammock MV (p = 0.0088) and ACHD (p = 0.0048) were strong predictors for poor
      event-free survival. CONCLUSION: MV repair for MVCM provides acceptable early and
      mid-term outcome in terms of mortality and freedom from reoperation. ACHD
      significantly reduce early and late postoperative survival and freedom from
      reoperation.

PMID- 12000153
TI  - Mitral repair in patients with severely calcified annulus: feasibility, surgery
      and results.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the feasibility and
      follow up data of extensive decalcification for mitral valve repair in patients
      with severely calcified mitral annulus, in order to avoid mitral replacement.
      METHODS: Between 1993 and 1998, among 2,318 patients who underwent mitral valve
      surgery at the Herz-Gefaess-Klinik GmbH, Bad Neustadt, a severely calcified
      mitral valve annulus was encountered in 30 patients (17 males, 13 females; mean
      age 60.7+/-14.6 years; range: 22 to 77 years). Nineteen patients (63%) were in
      NYHA class III or IV. Mitral valve repair was performed by temporary detachment
      of the leaflets, en-bloc resection of the annular calcium deposits and annular
      reconstruction. Concomitant procedures included coronary bypass grafting (n = 6),
      aortic valve replacement (n = 2) and tricuspid repair (n = 1). Follow up data
      were obtained by telephone interviews with cardiologists, family physicians and
      patients. RESULTS: Postoperative Doppler echocardiography at discharge from
      hospital showed satisfactory mitral valve function in all patients. No residual
      regurgitation was found in 25 patients (83%), and trivial regurgitation in five
      (17%). Follow up was 100% complete; mean follow up was 3.2+/-1.6 years (range: 4
      months to 6 years). There was one early death, and one late death, but no
      instance of annulus dehiscence. There were no thromboembolic complications, but
      two anticoagulation-related events. At the time of follow up, echocardiography
      was performed in 26 patients, and showed no residual regurgitation in 21 patients
      (81%) and trivial regurgitation in five (19%). Twenty-eight patients (93%) were
      in NYHA class I or II, and all described their quality of life as normal.
      CONCLUSION: These results show that aggressive and complete annulus
      decalcification, including complete temporary detachment of the leaflets, can be
      performed safely in patients with a severely calcified mitral valve annulus. The
      study also showed that initially good results remained stable for up to six years
      postoperatively in these repair patients. Hence, decalcification is a safe and
      rapid procedure that produces excellent results.

PMID- 12000154
TI  - Posterior mitral leaflet repair with a simple segmental annulus support: the
      'double-Teflon technique'.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aim was to present immediate and late
      results of a modified technique for mitral valve repair--the 'double-Teflon
      technique'. This consists of quadrangular resection of the posterior leaflet,
      annulus plication with 'pledgetted' stitches over a Teflon patch, and leaflet
      suture. METHODS: Seventy-two patients (41 males, 31 females; mean age 60.5+/-11.9
      years) with mitral insufficiency due to myxomatous degeneration and ruptured or
      elongated chordae tendineae underwent mitral valve repair with this technique.
      Fifteen patients (18%) had associated cardiovascular disease including coronary
      artery disease, aortic insufficiency, aortic stenosis and atrial septal defect.
      Operative, immediate postoperative and late operative echocardiographic data of
      the first 29 patients were analyzed. Actuarial survival was assessed using the
      Kaplan-Meier method. RESULTS: There was one operative death (1%). By the late
      postoperative period, 95% of survivors were in NYHA functional class I. There
      were no episodes of hemolysis or endocarditis; the linearized rate for
      thromboembolism was 1.4%/patient-year. Actuarial survival at 72 months was 94.5+/
      3.2%. Doppler echocardiography showed a significant decrease in mean left atrial
      diameter (p = 0.0001) and left ventricular diastolic diameter (p = 0.0003).
      CONCLUSION: Mitral valve repair with the 'double-Teflon technique' is associated
      with low operative mortality, satisfactory survival rates, and good clinical
      outcome.

PMID- 12000155
TI  - Eight-year experience of combined valve repair for mitral regurgitation and maze
      procedure.
AB  - BACKGROUND AND AIMS OF THE STUDY: Although atrial fibrillation (AF) is often
      associated with severe mitral regurgitation (MR), a simultaneous maze procedure
      for AF associated with repair of MR remains controversial. In this study, mid
      term results of combined mitral valve repair and the maze procedure were
      examined. METHODS: Between May 1992 and April 2001, 85 patients (61 males, 24
      females) underwent valve repair for MR and the maze procedure. Mean age at
      surgery was 61.8+/-9.1 years; mean follow up was 4.7+/-2.3 years. Valve lesions
      were anterior in 26 patients (31%), posterior in 31 (36%), anterior + posterior
      in 23 (27%), and simple dilated annulus in five (6%). Chordal replacement with
      expanded PTFE sutures was performed in 40 patients (47%), and leaflet resection
      in 41 (48%). Ring annuloplasty was also applied in 61 patients (72%). Associated
      procedures were tricuspid valve annuloplasty in 33 (36%), coronary artery bypass
      grafting in four, atrial septal defect closure in two, aortic valve repair in
      one, and resection of abnormal septum in the left atrium in one. RESULTS: There
      was one hospital death (1%), and one late death (1%). Reopening the chest for
      bleeding was necessary in six cases (7%). One thromboembolic episode was detected
      during follow up (0.25%/patient-year). Reoperation for MR was performed in three
      patients (4%). Actuarial event-free survival rate was 90.0+/-6.4% at eight years.
      Sinus rhythm was regained in 68 patients (81%), and atrial A-wave was detected in
      57 (68%) by pulsed Doppler study. Postoperative left ventricular diastolic and
      systolic dimensions were significantly (p = 0.001 and p = 0.017) smaller in
      patients who restored sinus rhythm than in those who did not (48.6+/-4.6 versus
      54.6+/-4.7 mm, and 33.0+/-6.0 versus 38.1+/-6.9 mm). CONCLUSION: Combined mitral
      valve repair for MR and the maze procedure showed satisfactory midterm results.
      Postoperative sinus rhythm conversion by the maze procedure may reduce left
      ventricular size, and the incidence of thromboembolic episodes in mitral valve
      repair.

PMID- 12000156
TI  - Qualitative and quantitative evaluation of mitral valve morphology by
      intraoperative volume-rendered three-dimensional echocardiography.
AB  - BACKGROUND AND AIM OF THE STUDY: Two-dimensional echocardiography (2DE) performed
      to evaluate mitral valve anatomy during valve repair has certain limitations and
      pitfalls. The study aim was to assess the feasibility, accuracy and incremental
      value of three-dimensional echocardiography (3DE), coupled with 2DE in evaluating
      mitral valve structure, before and after repair and pericardial posterior
      annuloplasty. METHODS: The site and extent of mitral valve prolapse, systolic and
      diastolic changes of mitral annular area were evaluated using 2D and 3D
      transesophageal echocardiography (TEE), both pre- and postoperatively in 34
      patients before and after mitral valve repair and pericardial posterior
      annuloplasty. RESULTS: Concordance between 2DE and surgery in evaluating
      prolapsing mitral valve scallops was 76% for the anterior leaflet and 75% for the
      posterior leaflet; for 3DE and surgery, concordance was 87% and 93% respectively.
      There was a significant reduction in maximal and minimal annular area after
      surgery, with a statistically significant difference between systolic-diastolic
      changes. CONCLUSION: 3DE, coupled with 2DE, is feasible and accurate in
      delineating the extent and location of prolapsing scallops of the mitral valve.
      The combined approach is also valuable in planning mitral valve surgery and
      evaluating the mitral valve annulus in vivo.

PMID- 12000157
TI  - Surgical treatment of mitral regurgitation associated with enlarged left
      ventricle.
AB  - BACKGROUND AND AIM OF THE STUDY: Few long-term results exist of mitral valve
      replacement (MVR) in patients with chronic mitral regurgitation (MR) and severely
      enlarged left ventricle. Hence, the present study was conducted to provide
      additional data in this respect. METHODS: Between April 1988 and September 2000,
      45 patients (28 males, 17 females; mean age 33.8+/-10.5 years; range: 13-58
      years) with a left ventricular (LV) diastolic diameter (LVDD) >70 mm underwent
      MVR at Anzhen Hospital. MR was rheumatic in origin in 36 patients (80%) and
      congenital in nine (20%). Thirteen patients were in NYHA class II, and 32 in
      classes III -IV. The cardiothoracic ratio was 0.64+/-0.12 (range: 0.47-0.84). The
      ECG showed LV hypertrophy to be present in all patients. Echocardiography showed
      severe MR and LV hypertrophy in all patients: LVDD was 76.3+/-4.1 mm (range: 70.2
      89.6 mm). MVR was performed under hypothermic cardiopulmonary bypass. RESULTS:
      Two of 45 patients died perioperatively (mortality rate 4.4%). At two weeks after
      surgery, echocardiography showed a reduction in LVDD (from 76.3+/-6.5 to 65.0+/
      5.2 mm) (p <0.01). Follow up was completed in 37 patients (82%). Mean follow up
      was 4.69 years (range: 1-12.33 years). Nine patients were in NYHA class I, 21 in
      class II, and five in class III. Late mortality was 5%. LVDD was further
      decreased at late control from 76.3+/-6.5 to 60.0+/-6.1 mm (p <0.001).
      CONCLUSION: MVR is indicated in patients with mitral insufficiency and highly
      dilated ventricles. In addition, perioperative mortality was acceptable and late
      results satisfactory. Moreover, the intervention has the potential to reduce
      severe LV dilation, and in some cases to revert ventricular size to normal.

PMID- 12000158
TI  - Neurohormones in mitral stenosis before and after percutaneous balloon mitral
      valvotomy.
AB  - BACKGROUND AND AIM OF THE STUDY: The hormonal response to percutaneous balloon
      mitral valvotomy (PBMV) has been described in patients in sinus rhythm (SR) and
      with atrial fibrillation (AF). The study aim was to evaluate the effect of
      hemodynamic parameters and PBMV on atrial natriuretic factor (ANF) secretion and
      plasma renin activity (PRA) in mitral stenosis in SR and AF. METHODS: Thirty-one
      patients (26 females, five males; mean age 50.5+/-14 years) with pure rheumatic
      mitral stenosis underwent PBMV. Fourteen patients had AF, and 17 were in SR. PRA
      and ANF were measured 24 h before, and at 30 and 60 min, 24 h and one month after
      PBMV, after resting in a supine position for > or =2 h. Digitalis and diuretics
      were withdrawn 48 h before sampling; neither had patients received ACE inhibitors
      or beta-blockers during the previous month. RESULTS: PBMV was successful in all
      cases, without complication. Mitral valve area was increased and wedge pressure
      decreased in both groups after PBMV. In AF patients, neither PRA nor ANF were
      significantly affected before and after PBMV; in SR patients, ANF was decreased
      and PRA increased significantly, notably 24 h after PBMV. The cardiac index was
      increased in both groups, but was distinctly lower in AF patients both before and
      after PBMV. CONCLUSION: Despite similar hemodynamic results, reversal of the
      hormonal pattern after PBMV occurred only in SR patients, most likely because in
      AF patients a low cardiac index elicits a hormonal response similar to heart
      failure. This abnormal hormonal pattern may limit functional recovery after PBMV;
      hence, PBMV is best attempted while patients are still in SR.

PMID- 12000159
TI  - Relationship between resting parameters of the mitral valve and exercise capacity
      in patients with mitral stenosis: can the diastolic filling period predict
      exercise capacity?
AB  - BACKGROUND AND AIMS OF THE STUDY: In order to provide patients with better
      exercise capacity, interventional therapy to the mitral valve is often carried
      out in mitral stenosis (MS). Hence, it is crucial to determine exercise capacity
      before deciding on the time of intervention. The study aim was to demonstrate
      whether resting parameters of the mitral valve, notably left ventricular
      diastolic filling period (LVDFP) and mitral valve resistance (MVR), relate to
      restricted exercise capacity. METHODS: Forty-six patients (30 females, 16 males;
      mean age 44+/-11 years; range: 33-55 years) with rheumatic MS were enrolled.
      Exercise capacities of patients were grouped according to NYHA classification and
      maximal exercise tolerance values obtained using exercise testing. Exercise
      capacity in male patients was quantified. Relationships between patient variables
      and exercise capacity were evaluated using simple linear regression analysis. In
      order to identify determinants of exercise capacity, a discriminate multivariate
      analysis was performed with variables, which were found to correlate
      significantly in the univariate analysis. RESULTS: There were no correlations
      between echo score, MVR, planimetric mitral valve area (MVA), MVA obtained by the
      pressure half-time method or calculated by the continuity equation, and
      transmitral mean gradient and exercise capacity classes as defined by both NYHA
      and exercise testing. The only predictor of exercise capacity class determined by
      discriminate multivariate analysis using the significant parameters in the linear
      regression analysis was LVDFP. The quantified exercise capacity in male patients
      correlated only with LVDFP (r = 0.64, p = 0.008). CONCLUSION: Exercise capacity
      cannot be predicted using routine resting parameters of the mitral valve
      (including MVR) in patients with MS. In this respect, the LVDFP may be of value.

PMID- 12000160
TI  - Beta-blockade and exercise capacity in patients with mitral stenosis in sinus
      rhythm.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to determine whether beta
      blocker treatment (atenolol) improves cardiopulmonary exercise performance and
      ventilatory response in patients with mitral stenosis in sinus rhythm. METHODS: A
      prospective study comparing the results of cardiopulmonary exercise tests (CPETs)
      was performed before and after atenolol therapy in 17 patients in NYHA classes I
      and II with mitral stenosis in sinus rhythm. Transthoracic echocardiography was
      performed pre-study, and left ventricular diameters, ejection fraction and mitral
      valve area monitored. CPETs (Naughton protocol) were performed by two different
      investigators before and after one-week atenolol therapy (50 mg/day). The second
      investigator was blinded to the result of the baseline test. O2 consumption, CO2
      production, ventilatory parameters and respiratory exchange ratios were measured
      on line. RESULTS: Maximal O2 uptake (VO2max) did not differ significantly before
      and after beta-blockade (median 16.8 and 15.0 ml/kg/min, respectively. Median
      heart rate at rest (72 versus 55 beats/min; p = 0.0003) and during peak exercise
      (153 versus 105 beats/min; p = 0.0003), and anaerobic threshold (10 versus 8.9
      ml/kg/min; p = 0.02) were lower with beta-blockade compared with the baseline
      state. Minute ventilation at maximum exercise (41 versus 40 l/min) and
      ventilatory equivalent for CO2 (34 versus 35) were unchanged with atenolol
      therapy, indicating no improvement in ventilatory performance. When patients were
      grouped into those in whom VO2max was improved with atenolol therapy (n = 7) and
      those in whom it was impaired (n = 10), there were no inter-group differences
      with respect to age, left ventricular function, severity of mitral stenosis, NYHA
      class and grade of beta-blockade reached. Four patients felt symptomatically
      worse during atenolol treatment (lower NYHA functional class). CONCLUSION: Beta
      blockade does not improve exercise tolerance in patients with mitral stenosis in
      sinus rhythm. In addition, ventilatory performance does not change with
      treatment.

PMID- 12000161
TI  - Value of exercise testing to evaluate the indication for surgery in asymptomatic
      patients with valvular aortic stenosis.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess the value of
      exercise stress testing in identifying asymptomatic patients with moderate or
      severe valvular aortic stenosis (AS). These patients generally develop symptoms
      during follow up, and require valvular replacement surgery (VRS) at one to three
      years after single symptom-limited exercise stress testing. Limited data are
      available on predictors of outcome in asymptomatic patients with valvular AS. A
      single symptom-limited exercise stress test might offer more precise risk
      stratification of patients referred for cardiological evaluation. METHODS: The
      safety and diagnostic accuracy of exercise testing to predict symptom development
      and need for surgery was assessed prospectively in 30 asymptomatic patients (mean
      age 62+/-14 years) with valvular AS. Twenty patients had moderate AS (mean
      Doppler gradient 30-49 mmHg), and 10 severe AS (gradient > or =50 mmHg). Patients
      underwent a symptom-limited maximal exercise test with upright bicycle ergometry.
      There were no complications during and after exercise testing. All patients were
      followed up for at least 36 months. RESULTS: Ergometry was abnormal in 18
      patients (60%); two patients had a fall in systolic blood pressure, one patient
      had a fall in systolic blood pressure with angina and ECG signs of myocardial
      ischemia, one had angina and ECG signs of myocardial ischemia, three patients had
      ECG signs of myocardial ischemia without symptoms, and 11 had dyspnea at low
      workload. During the following 12 months all patients with a normal exercise test
      remained asymptomatic (negative predictive value 100%). Ten of the 18 patients
      with abnormal exercise test experienced symptoms and required VRS, but eight did
      not (positive predictive value 55%). After 36 months, only two of 12 patients
      with a normal exercise test developed symptoms and required VRS (negative
      predictive value 83%); among subjects with abnormal exercise test, four of 18
      required VRS. At three years after exercise testing, 10 patients with a normal
      exercise stress test and four with an abnormal test did not require VRS as they
      remained asymptomatic (positive predictive value 78%). There was no statistically
      significant difference in valvular aortic area, maximal and mean gradient between
      patients with normal and abnormal exercise tests. CONCLUSION: Exercise stress
      testing may be performed safely in asymptomatic patients with moderate or severe
      valvular AS. Tests which meet criteria for normal patients allow physicians
      confidently to postpone VRS and to suggest a simple, cost-effective method of
      follow up in such cases. An abnormal test may reveal symptoms or identify a
      population for closer follow up.

PMID- 12000162
TI  - Management of patients with asymptomatic moderate aortic stenosis undergoing
      coronary artery bypass grafting.
AB  - BACKGROUND AND AIMS OF THE STUDY: Manual decalcification of the aortic valve was
      performed systematically in a prospective series of patients with asymptomatic
      moderate aortic stenosis (AS) undergoing coronary artery bypass grafting (CABG).
      This study addressed two main issues: (i) whether aortic valve decalcification is
      a good option to relieve moderate AS; and (ii) whether the natural progression of
      AS may be delayed by manual valve debridement when surgery is indicated for
      coronary disease. METHODS: Between October 1997 and March 2001, 14 adult patients
      with moderate AS underwent concomitant surgical repair of the aortic valve during
      CABG. Manual valve debridement with restoration of cusp mobility was attempted.
      Calcified deposits were removed by careful dissection. All patients underwent
      myocardial revascularization; a mean of 2.38 grafts was performed per patient.
      RESULTS: Immediately after surgery, mean aortic valve area index (AVAI) was
      improved, from 0.56+/-0.12 to 1.43+/-0.25 cm2/m2. Patients with the slowest
      recalcification rates were those with a postoperative/preoperative AVAI ratio of
      1.6 to 2.4, those in whom the degree of postoperative aortic insufficiency was
      very similar to the degree of preoperative regurgitation, and those in whom the
      preoperative AVAI was >0.55 cm2/m2. CONCLUSION: Manual aortic valve debridement
      for moderate AS is a good option when surgery must be performed for coronary
      disease; the best results were obtained in patients with senile stenosis of a
      tricuspid aortic valve with an AVAI of 0.55-0.9 cm2/m2.

PMID- 12000163
TI  - Influence of patient age and implantation technique on the probability of re
      replacement of the homograft aortic valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Results of valve rereplacement (reoperation) in
      898 patients undergoing aortic valve replacement with cryopreserved homograft
      valves between 1975 and 1998 are reported. The study aim was to provide estimates
      of unconditional probability of valve reoperation and cumulative incidence
      function (actual risk) of reoperation. METHODS: Valves were implanted by
      subcoronary insertion (n = 500), inclusion cylinder (n = 46), and aortic root
      replacement (n = 352). Probability of reoperation was estimated by adopting a
      mixture model framework within which estimates were adjusted for two risk
      factors: patient age at initial replacement, and implantation technique. RESULTS:
      For a patient aged 50 years, the probability of reoperation in his/her lifetime
      was estimated as 44% and 56% for non-root and root replacement techniques,
      respectively. For a patient aged 70 years, estimated probability of reoperation
      was 16% and 25%, respectively. Given that a reoperation is required, patients
      with non-root replacement have a higher hazard rate than those with root
      replacement (hazards ratio = 1.4), indicating that non-root replacement patients
      tend to undergo reoperation earlier before death than root replacement patients.
      CONCLUSION: Younger patient age and root versus nonroot replacement are risk
      factors for reoperation. Valve durability is much less in younger patients, while
      root replacement patients appear more likely to live longer and hence are more
      likely to require reoperation.

PMID- 12000164
TI  - The ross procedure for replacement of the bicuspid aortic valve: mid-term results
      from 55 consecutive cases.
AB  - BACKGROUND AND AIM OF THE STUDY: A congenitally dysfunctioning bicuspid aortic
      valve may require surgical treatment in children and young adults. This
      retrospective study evaluated mid-term clinical results obtained with the Ross
      procedure in this patient group. METHODS: Between July 1994 and December 2000, 55
      patients (48 males, seven females; mean age 27+/-10 years; range: 7-49 years)
      underwent replacement of a diseased bicuspid aortic valve (stenosis in six cases
      (11%); insufficiency in 36 (65%); mixed lesion in 13 (24%)) with a pulmonary
      autograft. Mean NYHA functional class was 1.7. Five patients (9%) had healed
      endocarditis and six (11%) had previous cardiac surgery. The autograft was
      inserted as a subcoronary implant in two cases (4%), as a root in 40 (73%), and
      as a cylinder in 13 (23%). The right ventricular outflow tract was reconstructed
      with a cryopreserved pulmonary homograft in all cases. Mean cardiopulmonary
      bypass and aortic cross-clamp times were 207+/-34 min and 162+/-18 min,
      respectively. RESULTS: No early or late deaths had occurred at a mean follow up
      of 31+/-19 months. Two patients (4%) were re-explored for bleeding. Four patients
      (7%) experienced intraoperative coronary complications which resolved without
      sequelae. Two-dimensional echocardiographic evaluation of neoaortic valve
      competence at six months revealed no evidence of aortic valve regurgitation in 46
      patients (84%), trivial regurgitation in seven (13%), mild regurgitation in one
      patient (2%), and moderate regurgitation in one patient. The latter patient
      (subcoronary implant) required reoperation. At six months, the degree of
      regression of left ventricular mass compared (versus preoperative) was 34+/-13%
      (p <0.05). Three patients (5%) showed mild dilatation (>4 cm) of the neoaortic
      root after two years follow up. All patients are currently asymptomatic, in NYHA
      class I, and enjoy a normal social lifestyle. CONCLUSION: The Ross procedure may
      be offered as a low-risk alternative in adolescents and young adults with a
      bicuspid aortic valve. Although the inclusion cylinder technique might help to
      prevent root dilatation, continued patient evaluation with regard to root sizing,
      evidence of neoaortic valve degeneration and homograft dysfunction is required in
      the long term.

PMID- 12000165
TI  - Distensibility of the pulmonary autograft under systemic pressure.
AB  - BACKGROUND AND AIMS OF THE STUDY: Although the Ross procedure has recently been
      recognized as one of the best replacements of the aortic valve, regurgitation has
      occasionally been observed with dilatation of the sinotubular junction (STJ)
      and/or basal ring (BR). This study was designed to evaluate the native
      distensibility of the free pulmonary root under systemic pressure. METHODS:
      Pulmonary arterial grafts (n = 7) were taken from pig hearts and pressurized (20
      100 cmH2O) with crystal sensors attached around the STJ and BR. Dimensions of the
      STJ and BR were measured using a digital 3-D ultrasonic sonomicrometer at
      different pressures (20-100 cmH2O) with and without the STJ and/or BR plicated
      with felt-strip to prevent overdistension. Valve insufficiency was evaluated
      macroscopically and endoscopically. RESULTS: All grafts showed no obvious valve
      insufficiency at 20 cmH2O. Grafts pressurized at 100 cmH2O showed 125+/-6% and
      113+/-5% enlargement of dimensions compared with baseline (20 cmH2O) data at the
      STJ and BR respectively, with recognizable insufficiency. When the STJ was
      plicated to prevent overdistension at 100 cmH2O with less dilated BR (106%), mild
      excentric insufficiency was observed. In case of the BR plicated at 100 cmH2O
      with a less dilated STJ (112%), central slight regurgitation was observed. Both
      the STJ and BR plications resulted in no recognizable regurgitation. CONCLUSION:
      Free pulmonary arterial grafts were remarkably enlarged under systemic pressure
      with recognizable valve insufficiency; this could be prevented by maintaining the
      original dimensions of the graft STJ and BR.

PMID- 12000166
TI  - Impact of small valve size on hemodynamics and left ventricular mass regression
      with the Toronto SPV stentless aortic bioprosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: The hemodynamic performance of stentless aortic
      bioprostheses has been previously well described. Because the potential for
      prosthesis-patient mismatch is greatest for small valves in the aortic position,
      the present study sought to compare the hemodynamic performance and degree of
      left ventricular (LV) mass regression between valve sizes for the Toronto SPV
      valve, with special interest in measures of relief of LV outflow obstruction
      afforded by the smallest valves. METHODS: This study included 257 patients (178
      men, 79 women; mean age 63.5+/-11.4 years; range: 34-93 years) from six
      investigative centers with complete echocardiography/Doppler data obtained
      through three years. Valve sizes implanted were 21 mm (n = 11), 23 mm (n = 23),
      25 mm (n = 58), 27 mm (n = 83), and 29 mm (n = 82). Echocardiography was
      performed at discharge, six months, one year, and yearly thereafter, and
      interpreted in a centralized core laboratory. Mean gradient, effective orifice
      area (EOA), indexed EOA, and absolute and percent change in LV mass index were
      used as markers of hemodynamic performance. RESULTS: For all valve sizes, mean
      and peak gradients fell and EOA increased early after surgery. There were no
      differences between groups in the degree to which gradients fell, and EOA
      increased from discharge to one year follow up. At one year, indexed EOA was 0.9
      cm2/m2 for valve sizes 21 and 23 mm, and 1.0-1.2 cm2/m2 for sizes 25, 27 and 29
      mm. There was statistically significant LV mass regression for all valve sizes (p
      <0.05), and no differences between valve sizes in the magnitude of absolute or
      percent change in LV mass index between baseline and three years. CONCLUSION: The
      Toronto SPV valve demonstrates excellent parameters of hemodynamic performance
      for all valve sizes, including the smallest valves used in only a minority of
      patients. Findings of indexed EOA > or = 0.9 cm2/m2, and equivalent degrees of LV
      mass regression for all valve sizes, reinforces the excellent hemodynamic
      performance of stentless aortic bioprostheses, and suggests that prosthesis
      patient mismatch should be minimized with these valves.

PMID- 12000167
TI  - Bovine jugular vein as right ventricle-to-pulmonary artery valved conduit.
AB  - BACKGROUND AND AIMS OF THE STUDY: The reduced availability of homografts and
      investigations into the ideal valved conduit have prompted a search for
      alternative options. This prospective study evaluated the Contegra, a new
      biological valved conduit consisting of a glutaraldehyde-preserved heterologous
      bovine jugular vein having a trileaflet venous valve. METHODS: Between April 1999
      and May 2001, 26 patients (mean age 13.5+/-12.5 years; range: 4 months to 43
      years), of mean body weight 33.9+/-26.7 kg (range: 4.0-91.0 kg), underwent
      implantation of a Contegra valved conduit for the following diagnoses: pulmonary
      valve replacement during Ross operation (n = 11), pulmonary atresia with
      ventricular septal defect (n = 6), tetralogy of Fallot (n = 3), truncus
      arteriosus (n = 3), Taussig-Bing syndrome (n = 2), and pulmonary valve
      regurgitation (n = 1). Conduit size was 14 mm in two patients, 16 mm in four, 18
      mm in three, 20 mm in three, and 22 mm in 14. Mean cardiopulmonary bypass time
      was 156+/-33 min (range: 105-233 min), and mean aortic cross-clamp time 79+/-29
      min (range: 0-128 min). RESULTS: There were no hospital deaths. During a mean
      follow up of 14.7+/-6.9 months (range: 1-26 months) there was one late death (4%
      mortality) that was unrelated to the valved conduit. Three children underwent
      reoperation; in all cases this was nonconduit-related. All 25 late survivors are
      currently free from reoperation and complications due to presence of the conduit.
      Echocardiographically monitored valve regurgitation was absent in 12 cases,
      trivial in nine and mild in four. The discharge situation was maintained during
      systematic follow up. No difference was found between the pressure gradient at
      discharge and at the last follow up. CONCLUSION: The new conduit provided
      consistently good results during its first two years of use. The main advantages
      were: (i) excellent off-the-shelf availability; (ii) large variety of available
      sizes (12 to 22 mm internal diameter); (iii) easy tailoring and suturing; (iv)
      adequate hemodynamics; (v) no need for proximal or distal extension; and (vi)
      reduced cost (half that of a conventional homograft).

PMID- 12000168
TI  - Dissected aortic sinuses repaired with gelatin-resorcin-formaldehyde (GRF) glue
      are not stable on follow up.
AB  - BACKGROUND AND AIM OF THE STUDY: The chemical glue, gelatin, resorcin and
      formaldehyde (GRF) is widely used to obliterate the false lumen of acute
      dissected aortic wall tissue. METHODS: A retrospective review of 41 consecutive
      patients operated upon for ascending aortic dissection between 1993 and 2000 was
      conducted. This study focused on 19 patients with acute aortic dissection in whom
      the aortic valve was resuspended and GRF glue used in the proximal aortic
      sinuses. These patients were compared with ascending aortic dissection patients
      in whom the aortic valve was not resuspended. In total, nine acute and 13 chronic
      dissections were performed in which aortic valve replacement, valve-sparing root
      reconstruction (without GRF glue), or no aortic valve surgery was carried out.
      RESULTS: The operative mortality for ascending aortic dissections was 24.4%;
      identified risk factors included the specific surgeon involved. Third-degree
      heart block occurred only in patients in whom GRF glue was used in the proximal
      aortic sinus (15% incidence). Operative survivors in whom the aortic valve was
      resuspended and GRF glue used in the proximal aortic sinus, had a 64% incidence
      of late recurrent aortic regurgitation requiring reoperation due to recurrent
      aortic sinus aneurysm formation with or without recurrent proximal aortic
      dissection. No recurrence of aortic regurgitation or proximal disease occurred in
      the other two groups (p <0.01). Actuarial survival of patients in whom the aortic
      valve was resuspended with GRF glue was 52.1+/-11.6% at five years and 27.8+/
      14.3% at eight years, compared with 55.6+/-16.6% at five years if the aortic
      valve was not resuspended using GRF glue. CONCLUSION: The use of GRF glue to
      repair acute dissected aortic sinuses combined with the resuspension of the
      aortic valve is associated with an unacceptable incidence of failure of aortic
      valve repair and recurrence of aortic regurgitation. It may be more appropriate
      to resect all acute dissected aortic sinus tissue.

PMID- 12000169
TI  - Cardiac valve reoperations: analysis of operative risk factors in 154 patients.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aim was to evaluate the operative
      risks of reoperation on heart valve prostheses. METHODS: Between January 1985 and
      December 2000, 154 patients (79 males, 75 females, mean age 61.2+/-9.5 years)
      underwent cardiac valve reoperation for which indications were prosthetic failure
      (n = 133; prosthetic mitro-aortic dysfunction occurred in 16 cases), native valve
      disease in patients with a previous prosthetic valve implantation (n = 12), and
      both situations concomitantly (n = 9). Total valve replacements numbered 161 (64
      in the aortic position, 96 in the mitral position, and one in the tricuspid
      position). There were 18 valve repairs (eight in the mitral position, 10 in the
      aortic position). One patient underwent prosthesis thrombectomy (mechanical
      valve). RESULTS: Overall operative mortality was 8.4% (n = 13); emergency
      operation (p <0.002), advanced NYHA class (p <0.026), indication for reoperation
      (p <0.026), gender (p <0.016) and number of previous reoperations (p = 0.05) were
      independent determinants for reoperation. Non-significant determinants were age
      and position of replacement. CONCLUSION: Correct planning of reoperation timing
      reduces operative risks due to NYHA class (3.8% mortality rate for class II-III
      versus 21.7% for class IV), and to urgent-emergency procedures (35.7% mortality
      versus 6.5% for elective operations). The high operative risk of prosthesis
      thrombosis is a deterrent to implanting mechanical prostheses in patients with
      disorders of hemostasis.

PMID- 12000170
TI  - Four years' experience with the Edwards-Tekna bileaflet valve prosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: Although over 20,000 Edwards-Duromedics valves
      were implanted worldwide between 1982 and May 1988, use of the valve was
      voluntarily suspended by the manufacturer in May 1988 on the basis of reported
      leaflet escapes. In 1990, a modified version was introduced to the market, the
      Edwards-Tekna. The study aim was to evaluate the short-term outcome with this
      revised valve. METHODS: Between 1994 and 1998, 137 patients (67 males, 70
      females; mean age 36.3+/-9.1 years) underwent heart valve replacement with the
      Edwards-Tekna prosthesis. Among these patients, 72 had isolated mitral valve
      replacement, 59 isolated aortic valve replacement, and six double-valve
      replacement. RESULTS: Early hospital mortality was 0.72% (n = 1). Follow up was
      95% complete (129/136 patients discharged from hospital). Mean follow up was
      24.9+/-10.5 months (range: 2 to 48 months); total follow up was 282.9 patient
      years (pt-yr). Actuarial freedom from complications at two-year follow up and
      linearized incidence (%/pt-yr) of these events were: late mortality 87.8+/-8.5%
      (1.77%/pt-yr); thromboembolism 89.8+/-4.9% (2.12%/pt-yr); anticoagulation-related
      bleeding 97.8+/-1.5% (0.71%/pt-yr); prosthetic valve endocarditis 99.1+/-0.9%
      (0.35%/pt-yr); valve-related mortality 98.2+/-1.2% (0.71%/pt-yr); and valve
      related morbidity and mortality 85.0+/-5.0% (4.24%/pt-yr). There was no
      structural valve failure such as leaflet escape in this series. Clinically
      significant hemolysis was not encountered (mean postoperative plasma LDH level
      345+/-124 IU/l). Preoperatively, 69% of patients were in NYHA classes III/IV; at
      two years postoperatively 90% of survivors were in classes I/II. CONCLUSION: The
      Edwards-Tekna mechanical valve prosthesis has shown excellent overall clinical
      performance in the short term, though long-term data are needed to confirm its
      durability.

PMID- 12000171
TI  - Improved statistical characterization of prosthetic heart valve hydrodynamics
      using a performance index and regression analysis.
AB  - BACKGROUND AND AIMS OF THE STUDY: The ISO 5840 Standard (Cardiovascular implants 
      Cardiac valves) currently requires a minimum of three test samples per size for
      hydrodynamic testing. Typically, the only statistical analysis performed is a
      descriptive analysis, with the mean (+/- SE) given for each size and cardiac
      output (CO). The study aim was to develop better statistical methods,
      incorporating regression analysis of a performance index, equal to the effective
      orifice area divided by the tissue annulus area. The analysis is performed on the
      full dataset, with size and CO as independent variables. METHODS: Hydrodynamic
      data of Ionescu-Shiley pericardial valves from a published study were used to
      compare the two analysis methods. Three samples each of size 19, 23 and 27 mm
      valves were tested at COs of 4.2, 5.6, 7.0 and 8.4 l/min. Descriptive statistics
      were performed for each size and CO. Regression analysis was also performed on
      the full dataset. Confidence intervals (CI) were calculated for each statistical
      method and compared. RESULTS: The regression equation that best fitted the data
      was: Performance Index (PI) = -1.63 + (0.011 x CO) + (0.167 x size) - (0.0036 x
      size2). All four parameter estimates were significantly different from zero (p
      <0.02). The SE of the mean was 0.015 for COs of 4.2 or 8.4 l/min, and 0.013 for
      COs of 5.6 or 7.0 l/min, less than that of nine of 12 of the individual
      descriptive analysis. CI for the regression analysis were substantially tighter,
      averaging one-third the width of those of the descriptive statistics. CONCLUSION:
      The tighter CI resulting from the regression analysis allows a better comparison
      of the PI to an objective performance criterion. Such methods should be
      considered for inclusion in the new version of the ISO 5840 standard for
      prosthetic heart valves.

PMID- 12000172
TI  - Evaluation technique for bileaflet mechanical valves.
AB  - BACKGROUND AND AIMS OF THE STUDY: Several techniques were utilized to evaluate
      the performance of bileaflet mechanical heart valves and improve upon current
      valve designs. METHODS: Particle image velocimetry (PIV), computational fluid
      dynamics (CFD) and video analysis were used to evaluate St. Jude Medical (SJM)
      and ATS valves in an abrupt enlargement outlet chamber. Video analysis and PIV
      provided information on the opening angle of the leaflets and 2D velocity fields.
      PAM-FLOW CFD software was used to predict flow through the valves with leaflets
      in the fully open position, which corresponds to steady flow conditions in the
      experimental study. The ATS valve was also modeled at its reported incomplete
      leaflet opening angle, and with an orifice modification. Additional CFD
      techniques were employed to find the natural opening angle of the ATS valve.
      RESULTS: In steady and pulsatile flow, the SJM leaflets opened completely. PIV
      showed three fairly uniform jets passing through the SJM valve. CFD analysis of
      the pressure distribution across the SJM valve showed a resultant moment in the
      open direction, indicating that the leaflets were held against the open stops at
      85 degrees. In both steady and pulsatile flow, the leaflets in the ATS valve did
      not open to the designed opening angle. From video analysis, the ATS leaflet
      opening angle was estimated at 72-76 degrees. PIV showed that the incomplete
      opening angle of the ATS leaflets produced a large wake region behind the
      leaflets, and lateral jets that impinged on the side walls of the test chamber.
      CFD analysis showed a pressure distribution across the ATS valve which produced a
      moment causing the leaflets not to open to 85 degrees. The equilibrium position
      of the leaflet was approximately 75 degrees. The leaflets in the CFD model opened
      to the full 85 degrees when the orifice was increased by 2 mm on the outflow
      side. CONCLUSION: The combination of techniques used in this study provided a
      method that will be useful in evaluating new valve designs. It was learned that
      leaflet position, pivot location and orifice height influence pressure
      distribution across the leaflets, thereby affecting the opening angle.

PMID- 12000173
TI  - Serum components stimulate pericardial tissue contraction.
AB  - BACKGROUND AND AIMS OF THE STUDY: Previous experiments have demonstrated the
      retraction and fibrosis of vital autologous pericardial flap implants in the
      descending aorta of sheep. An in-vitro model of pericardial tissue contraction
      was developed that showed healing reactions similar to those observed in the
      fresh in-vivo flap. Here, the component(s) of serum that stimulate tissue
      contraction were partially characterized. The molecular weight range and
      stability (heat and protease resistance) of the serum component(s) are described.
      Tissue contraction also requires de-novo protein synthesis. METHODS: Sections (1
      cm2) of sheep pericardium were incubated with fractionated, heat-treated, or
      protease-treated fetal bovine serum for 14 days. In addition, SDS-PAGE protein
      profiles were generated using tissues incubated with and without cycloheximide
      for up to 12 days. RESULTS: Tissue contraction was observed in molecular weight
      serum fractions > or =5 kDa, as well as in samples incubated with heat and
      protease-treated serum. SDS-PAGE showed the appearance of a protein band after
      day 4 during the process of tissue contraction that was absent in samples
      incubated with cycloheximide. CONCLUSION: Serum fractions > or =5 kDa stimulated
      protein synthesis and pericardial tissue contraction. The active component(s) was
      shown to be heat stable, but partially sensitive to protease. The addition of
      cycloheximide to the culture medium, shown previously to prevent pericardial
      tissue contraction, inhibited de-novo synthesis of the protein that appeared
      during the process of tissue contraction.

PMID- 12000174
TI  - Case report: fibroelastoma of the papillary muscle of the mitral valve:
      diagnostic implications and review of the literature.
AB  - A 77-year-old woman was found accidentally to be in atrial fibrillation. Two
      dimensional echocardiography revealed the presence of a mass attached to the
      anterior papillary muscle of the mitral valve. She was mildly symptomatic for
      dyspnea and asthenia. The patient was successfully operated on to excise the left
      ventricular mass and preserve the mitral valve apparatus. Morphological
      examination of the excised tissue led to a diagnosis of papillary fibroelastoma.
      Surgical treatment must be considered when such a tumor is diagnosed, even though
      asymptomatic, and especially if left-sided because of the high risk of systemic
      embolization.

PMID- 12000175
TI  - Asymmetric primary ringless repair of mitral valve endocarditis: a case report.
AB  - The case is presented of a patient with a large mitral valve vegetation. A
      technique of mitral valve repair involving ringless annuloplasty repair following
      bileaflet resection of the infected regions of the valve is described. No
      pledgets or prosthetic material were used in the repair. The patient recovered
      uneventfully, with trivial mitral regurgitation documented on post-repair
      echocardiography. This technique may suggest a method for early intervention in
      mitral endocarditis.

PMID- 12000176
TI  - Image of the month. Pannus-overgrowth in a Bjork-Shiley valve in the mitral
      position.

PMID- 12000177
TI  - In response to influence of HLA matching and associated factors on aortic valve
      homograft function.

PMID- 12000178
TI  - Image analysis of Transwell assays in the assessment of invasion by malignant
      cell lines.
AB  - This study aims to determine if layering of extracellular matrix (ECM) can
      achieve a physiological basement membrane thickness of 8 microm and to assess the
      use of paraffin wax-embedded Transwell plates coupled with digital image analysis
      as a means of determining invasion by malignant cell lines. Layers of Matrigel, a
      sarcoma-derived ECM was built to a concentration of 7.4 microg/mm2 in the upper
      chamber of a Transwell plate invasion assay. Two cell lines from extrahepatic
      bile duct adenocarcinoma were tested in serum-free growth medium. Conditioned
      medium was added to the lower chamber to act as a chemoattractant. Following
      attachment, cells were incubated for 48 h and the Matrigel-coated insert cut from
      its holder and fixed in 10% unbuffered formalin saline. Each insert was bisected
      and processed to paraffin wax. Serial levels were stained by haematoxylin and
      eosin. A Kontron image analysis system was used to measure the mean thickness of
      Matrigel for each cell line and the degree of invasion was assessed by measuring
      the depth to which cells had degraded the Matrigel. A mean thickness of 8 microm
      was achieved using 5.0 microg/mm2 for the OCUCh-LM1 cell line and 7.4 microg/mm2
      for the SKChA-1 cell line. No significant difference was seen in the ability of
      either cell line to degrade Matrigel. Immunocytochemistry for laminin and
      cytokeratin helped to identify ECM components and cells, respectively. In
      conclusion, digital image analysis of paraffin wax-embedded inserts can be used
      to determine the invasive capacity of various cell lines; immunocytochemistry may
      help to identify ECM components and cells; and the assay used to assess different
      cell lines and their ability to degrade Matrigel.

PMID- 12000179
TI  - In vitro testing of platinum-based drugs on a panel of human ovarian tumour cell
      lines.
AB  - Much improvement in the treatment of ovarian cancer has been achieved since the
      introduction of platinum compounds in the 1980s, with the result that single
      agent platinum-based therapy following primary surgery is now the standard
      treatment for advanced ovarian cancer. The main therapeutic effect of
      chemotherapy is based on the sensitivity of the patient's tumour to the drug.
      However, testing a new chemical compound on humans requires much care, time and
      resources, whereas prior testing of drugs on cancer cell lines may indicate those
      drugs particularly suited to treatment of a specific disease. This study
      investigates the actions of two established platinum-based chemotherapeutic
      agents (cisplatin and carboplatin) on a panel of 10 human ovarian cancer cell
      lines. Each cell line was plated onto 96-well tissue culture plates, incubated
      for 72 hours with the drug, formalin-fixed and then assessed using the methylene
      blue colorimetric microassay to detect viable cells. The IC50 values for each
      cell line were calculated in order to assess the toxicity of each drug, and a
      wide range of responses were observed across the 10 cell lines investigated. This
      suggests that the panel reflected the heterogeneous nature of ovarian cancer, a
      malignancy in which a huge range of drug sensitivities can be seen even among
      tumours of the same histological type. The results indicate that the panel could
      be of use either as a primary screen to test new drugs against ovarian cancer or
      to investigate the drug resistance that is so common in this disease.

PMID- 12000180
TI  - Air flight-related thrombosis: reality or hype?

PMID- 12000181
TI  - Measurement of urine total sialic acid: comparison of an automated ultraviolet
      enzymatic method with a colorimetric assay.
AB  - An automated ultraviolet (UV) enzymatic assay for urine total sialic acid (SA),
      performed on a Cobas Fara analyser, is described and compared with the
      colorimetric Warren method, which is used widely to determine urine SA. Intra
      assay coefficient of variation (CV) for urine total SA determination was 0.83%
      for the UV assay and 3.5% for the Warren method. Inter-assay CVs were 1.8% and
      5.6%, respectively. Recovery of urine total SA ranged from 89% for the UV assay
      to 61% for the Warren method. Both were linear over a range of urine SA from 20
      to 240 mg/L The UV assay was automated, took approximately 20 min to produce a
      result and avoided the need for solvent extraction; however, the reagents were
      expensive in comparison to those required for the Warren method. Urine samples
      with a creatinine concentration > 14 mmol/L were diluted with distilled water to
      optimise SA recovery by the UV method. Urine SA:creatinine ratios for normals
      were 4.7 (+/- 1.7) g/mol with the Warren method and 4.5 (+/- 1.0) g/mol for the
      UV method. Similarly, in type-2 diabetic patients, urine SA:creatinine ratios
      were 7.6 (+/- 2.3) g/mol (P<0.001) and 8.5 (+/- 2.9) g/mol (P<0.001),
      respectively.

PMID- 12000182
TI  - Nitric oxide generation by peripheral blood cells in chronic renal failure.
AB  - Nitric oxide (NO), a labile free radical synthesised from L-arginine by the
      action of nitric oxide synthase (NOS), is said to be implicated in uraemic
      complications, such as infection and a tendency to bleed. In this study of NO
      production by peripheral blood cells, an increased level is seen in platelets
      from uraemic patients (both non-dialysed and haemodialysed) and a decreased level
      in leucocytes (neutrophils and monocytes). A negative correlation was noted
      between blood urea level and inducible NO in neutrophils and monocytes in uraemic
      patients not on dialysis. In contrast, haemodialysis appears to lead to an
      increase in inducible NO production in neutrophils and monocytes. Plasma NO
      levels were significantly increased in uraemic patients, compared with normal
      controls, and hemodialysis led to further increases. Superoxide dismutase (SOD)
      activity was significantly reduced in platelets, neutrophils and monocytes in the
      uraemic group. It is concluded that increased NO production by platelets may
      contribute to the bleeding tendency observed in uraemia, and high urea
      concentrations may contribute to the regulation of inducible NO production in
      leucocytes.

PMID- 12000183
TI  - Serum IgM to Chlamydia trachomatis in pregnancy: its usefulness for screening.
AB  - Asymptomatic infection with Chlamydia trachomatis represents an important health
      problem. A non-invasive diagnostic test to screen pregnant women is needed that
      is cost effective and can be used widely, especially in developing countries. In
      this setting, quantitation of antichlamydial IgM antibodies may offer an
      additional strategy for the control of C. trachomatis infection. The aim of this
      prospective study is to evaluate the quantitation of serum antichlamydial IgM
      antibodies, based on absorbance (A) values, in pregnant women for the prediction
      of C. trachomatis infection. Serum samples from a cohort of 148 pregnant women
      (first to third trimesters; age range: 18-35 years) presenting to the antenatal
      department at Safdarjang Hospital were tested for IgM antibodies specific to C.
      trachomatis by an enzyme-linked immunosorbent assay (ELISA) kit (Novum
      Diagnostics, Germany). Co-infection with other STD pathogens was ruled out. In
      this cohort, 85 (57.4%) pregnant women were found to be positive for IgM
      antibodies to C. trachomatis. Based on the cut-off value of the ELISA test
      (calculated as 0.558), pregnant women with an A value between 0.558 and 0.999 and
      those with a value > 1.000 were categorised as low positive (LP, n=41) and high
      positive (HP, n=44), respectively. The differences in mean A values for the LP
      versus negative groups (0.7504 versus 0.2249, P<0.05) and the HP versus negative
      groups (1.5353 versus 0.2249, P<0.05) were statistically significant. Maximum
      seroprevalence (44.4%, P<0.05) was found among those in the HP group in the first
      trimester of pregnancy. Multigravidae (34.4%, P<0.5) and multiparous (34.9%,
      P<0.5) pregnant women in the HP group were at an increased risk of chlamydial
      infection. As overall results indicated that pregnant women in the HP group were
      at higher risk, we stress the importance of large-scale screening of pregnant
      women for C. trachomatis infection, particularly in developing countries where
      sophisticated techniques for collection/diagnosis are as yet unavailable.

PMID- 12000184
TI  - Construction of a cDNA fragment library from SH-SY5Y cells using restriction
      display PCR.
AB  - A complementary DNA (cDNA) fragment library from SH-SY5Y cells is constructed
      using a restriction display polymerase chain reaction (RD-PCR) technique.
      Messenger RNA (mRNA) is extracted from SH-SY5Y cells and single-strand cDNA
      synthesised using an anchored oligo primer (dT18). The second strand is produced
      by nick translation. The double strands are cleaved with the restriction enzyme
      Sau3AI and the fragments ligated with universal linker. The products are
      amplified with universal primers and selected primers, ligated into the pMDI8-T
      vector, and then sequenced. The library constructed contained 136 subgroups, each
      comprising seven to 12 cDNA fragments. RD-PCR proved a simple, effective way to
      construct a cDNA library, and this will contribute to the investigation of gene
      expression in the neuron in future microarray studies.

PMID- 12000185
TI  - Seronegative spondarthritis and human leucocyte antigen association.
AB  - The human leucocyte antigen (HLA) B27 has been associated with seronegative
      spondarthritis universally, but the associations varies (19-94%) in different
      Indian population groups. It is possible that this variation is due to patient
      selection bias. Here, we use strict clinical, radiological and serological
      criteria to select 79 patients with seronegative spondarthritis (SSA) and compare
      them with 110 healthy, normal individuals from the same ethnic background. The
      standard National Institute of Health (NIH) microlymphocytotoxicity assay is used
      to evaluate HLA B27 status in both groups. Significant association between HLA
      B27 and AS disease was found (odds ratio [OR]: 72.22; P<0.0001; confidence
      interval [CI]=1.5-3.8) when compared to the control group. Furthermore, HLA B5
      was decreased when compared to the control group (OR: 0.39; P<0.01). Those in the
      20-40 age group were more vulnerable, with a male preponderance (7:1) over
      females. These findings confirm the strong association of the HLA B27 allele with
      various types of spondarthritis and suggest that allele detection would help in
      the diagnosis of AS where clinical presentation is unclear and in identifying
      family members at risk.

PMID- 12000186
TI  - How to detect current toxoplasma infection.
AB  - This study seeks to identify the best way to detect current toxoplasma infection
      for district general hospital laboratories. One hundred 'ordinary' and 174
      'difficult' sera are categorised into either an 'evidence' or 'no evidence' group
      for current toxoplasma infection. Twelve test protocols are investigated using
      different combinations of one whole antibody latex test (Eiken Toxoreagent), one
      in-house specific IgG enzyme-linked immunosorbent assay (ELISA) and three
      specific IgM assays (Toxo-ISAGA, in-house BAM ELISA IgM and Toxonostika ELISA M).
      The Eiken latex and in-house IgG assays produced significantly fewer false
      negative results than were obtained with the single IgM test or the IgG and IgM
      test protocols (P<0.05), but a greater number of false-positive results (102/274
      and 115/274, respectively). Of the IgM assay test protocols, the three IgM assays
      in combination produced the least number of false-negative results (1/274).
      However, a significantly greater number of false-positive results were produced
      than with one or two IgM tests or an IgG and any IgM test in combination
      (P<0.001). We recommend testing with three IgM tests, or a whole antibody (Eiken)
      or IgG-specific assay, and that positive or clinically important negative samples
      be referred to a reference laboratory for confirmation.

PMID- 12000187
TI  - Tandem mass spectrometry: the tool of choice for diagnosing inborn errors of
      metabolism?
AB  - The early diagnosis of inborn errors of metabolism (IEM) by laboratory-based mass
      screening is a prime example of preventive medicine. However, several factors
      restrict the range of IEM that can be screened for, and the numbers of people to
      whom it can be made available. Mass screening in the United Kingdom is limited
      primarily to that for phenylketonuria and congenital hypothyroidism. Ideally,
      extension of mass screening of neonates for additional clinically significant IEM
      is a desirable strategy. Tandem mass spectrometry (TMS) is a powerful and
      effective diagnostic technique and has been proposed as a means to realise this
      aim. Its main advantages are improved accuracy, sensitivity and specificity over
      existing methods, and its suitability for cost-effective multidisease IEM mass
      screening. The evolution, principles and applications of TMS are described, and
      the practical and clinical implications of extending diagnostic services for IEM
      using TMS are discussed.

PMID- 12000188
TI  - Proteomics and its impact upon biomedical science.
AB  - Proteomics is the protein equivalent of genomics and is the study of gene
      expression at a functional level. The proteome of an organism is the protein
      complement of its genome. However, unlike the genome, the proteome is dynamic: it
      varies according to the cell type and the functional state of the cell. In
      addition, the proteome shows characteristic perturbations in response to disease
      and external stimuli. Proteomics combines state of the art analytical methods
      with bioinformatics. Here, we review the concept and technology of proteomics
      with specific reference to applications in medical microbiology, cellular
      pathology, clinical chemistry, haematology/immunology, pharmacology and
      toxicology.

PMID- 12000189
TI  - Two Japanese urease-positive thermophilic campylobacters, CF89-12 and CF89-14,
      isolated in 1989 prove to be two distinct strains.

PMID- 12000190
TI  - Streptococcus pneumoniae: presumptive identification and reporting.

PMID- 12000191
TI  - Methicillin-resistant Staphylococcus aureus: laboratory detection methods in use
      in the Republic of Ireland and Northern Ireland.
AB  - There is no universally agreed laboratory protocol for the detection of
      methicillin-resistant Staphylococcus aureus (MRSA) and hence a variety of
      approaches are used. As part of an all-island survey of MRSA in the Republic of
      Ireland (the South) and Northern Ireland (the North), a questionnaire was
      circulated to 14 participating laboratories in the North and 49 in the South, to
      determine the methods used to isolate MRSA from clinical specimens, identify S.
      aureus and test for susceptibility to methicillin. Almost two-thirds (64%) of
      laboratories in the North but only 16% of laboratories in the South use
      enrichment culture. There is heavy reliance on commercial kits to confirm the
      identification of S. aureus in the South but all laboratories in the North use
      the staphylocoagulase test. More than 90% of all laboratories use a disc method
      for susceptibility testing and 71% of laboratories in the North supplement this
      with the E-test; however, a range of methicillin disk concentrations are in use.
      There is a need to review current laboratory methods used to detect MRSA, with
      follow-up audit on their implementation. Additional resources may be needed in
      some laboratories to comply with revised guidelines, and reference facilities are
      required to assess new commercially available techniques and to confirm the
      identification of unusual or difficult strains.

PMID- 12000192
TI  - Apolipoprotein E affects amyloid formation but not amyloid growth in vitro:
      mechanistic implications for apoE4 enhanced amyloid burden and risk for
      Alzheimer's disease.
AB  - The transition from the partially folded soluble Abeta monomer to insoluble Abeta
      amyloidfibrils is seminal to the formation and growth of amyloid plaques in
      Alzheimer's disease (AD). A detailed understanding of the role of AD risk factors
      in these processes is essential to understanding the physiochemical nature of
      this conformational rearrangement. The apolipoprotein E epsilon4 allele, a risk
      factor for AD, affects AD pathology by increasing amyloid burden relative to the
      much more common epsilon3 allele. In the present study, in vitro models were
      employed to probe the effect of these proteins on kinetically distinct steps in
      Abeta fibrillogenesis. Formation of Abeta amyloid was faster in the presence of
      apoE4 than apoE3, while growth of existing plaques was unaffected by either
      isoform. Further, experiments with Abeta stereoisomers establish that this effect
      of apoE3 is mediated through interaction with oligomeric fibrillogenic
      intermediates rather than through specific contacts with monomeric Abeta.
      Consistent with the altered pathology and enhanced risk for AD associated with
      inheritance of the epsilon4 allele, we conclude that APOE epsilon4 is a risk
      factor for AD not due to a pathological gain of function of apoE4 but to a loss
      of protective function of apoE3.

PMID- 12000193
TI  - Channel formation by serum amyloid A: a potential mechanism for amyloid
      pathogenesis and host defense.
AB  - Serum amyloid A (SAA) is a family of closely related apolipoproteins associated
      with high density lipoprotein (HDL). Subclasses of SAA isoforms are
      differentially expressed constitutively and during inflammation. During states of
      infection or inflammation, levels of HDL bound, acute phase isoforms of SAA rise
      as much as 1000-fold in the serum, suggesting that it might play a role in host
      defense. Following recurrent or chronic inflammation, an N-terminal peptide
      fragment of SAA known as amyloid A (AA) assembles into fibrils causing extensive
      damage to spleen, liver, and kidney, and rapidly progressing to death. In the
      present paper, we report the novel finding that a recombinant acute phase isoform
      variant of human SAA 1.1 (SAAp) readily forms ion-channels in planar lipid
      bilayer membranes at physiologic concentrations. These channels are voltage
      independent, poorly selective, and are relatively long-lived This type of channel
      would place a severe metabolic strain on various kinds of cells. Expression of
      human SAA 1.1 in bacteria induces lysis of bacterial cells, while expression of
      the constitutive isoform (human SAA4) does not. Secondary structural analysis of
      the SAA isoforms in dicates a strong hydrophobicity of the N-terminal of the
      acute phase isoform relative to the constitutive SAA4 isoform, which may be
      responsible for the bactericidal activity of the former, in keeping with the
      notion that SAA 1 targets cell membranes and forms channels in them. Channel
      formation may thus be related to a host defense role of acute phase SAA isoforms
      and may also be the mechanism of end organ damage in AA and other amyloidoses.

PMID- 12000194
TI  - A multicenter phase II trial of 4'-iodo-4'deoxydoxorubicin (IDOX) in primary
      amyloidosis (AL).
AB  - INTRODUCTION: 4'-Iodo-4'-deoxydoxorubicin (IDOX) has been reported to bind to and
      lead to the catabolism of amyloid deposits. A multicenter study attempted to
      develop a dosing schedule to confirm those results. METHODS: Patients with biopsy
      proven amyloidosis were required to have a cardiac ejection fraction > 50%,
      ventricular septal thickness < 20 mm, serum creatinine < 2.5 mg per dL, bilirubin
      < or = 2.0 mg per dL, neutrophils > 1,500 per microL, and platelets > 100,000 per
      microL. IDOX was administered intravenously over 1 hour at a dose of 15 mg per m2
      once a week for 4 consecutive weeks. This therapy was repeated every 3 months up
      to 4 times. RESULTS: Twenty-five previously treated and 15 untreated patients
      with primary amyloidosis (AL) received therapy. Fifteen patients had > 3 g of
      protein per day in the urine. Eleven patients had an ejection fraction < 60%.
      One, 2, 3, 4, and 5 organ systems were involved in 22, 10, 4, 3, and 1 patient,
      respectively. The median time between diagnosis and initiation of IDOX was 17.4
      months. There were 6 responses (15%). Twelve of the patients have died
      CONCLUSION: IDOX administered in this protocol was insufficiently active at the
      current dose.

PMID- 12000195
TI  - Transthyretin Thr60Ala Appalachian-type mutation in a Japanese family with
      familial amyloidotic polyneuropathy.
AB  - A Japanese case with familial amyloidotic polyneuropathy (FAP) associated with
      the transthyretin mutation Thr60Ala (Appalachian-type mutation) is described This
      is the first reported case of a non-Caucasian harboring this type of TTR
      mutation. The patient developed severe late-onset restrictive cardiomyopathy as
      well as sensorimotor and autonomic polyneuropathy, which were essentially similar
      to the previously reported clinical pictures of Appalachian-type FAP.

PMID- 12000196
TI  - Familial amyloid polyneuropathy with genetic anticipation associated to a
      gly47glu transthyretin variant in an Italian kindred.
AB  - The most frequent localization of amyloid in transthyretin (TTR) mutations is in
      the peripheral nerve, causing familial amyloidpolyneuropathy (FAP). It is
      generally accompanied by involvement of other organs such as the myocardium and
      kidney. To date, over 70 TTR point mutations have been reported in literature,
      with different phenotypes depending on the location of the mutation in the TTR
      gene. This paper deals with a point mutation in exon 2 position 47 of the TTR
      gene, encoding the substitution of glycine with glutamate. The mutation was found
      in an Italian family with 5 patients over 3 generations. The phenotype was
      characterised by peripheral neuropathy and autonomic dysfunction, associated in
      some patients with cardiomyopathy and renal involvement. The symptoms were very
      severe and the patients did not survive long, thus suggesting the aggressive
      nature of the pathological process. Moreover, in the succeeding generations of
      this family, there was genetic anticipation in the age of onset of the disease.

PMID- 12000197
TI  - Globular amyloid deposits in the wall of the gastrointestinal tract: report of
      six cases.
AB  - Amyloid deposition in the gastrointestinal tract basement membrane, lamina
      propria, and blood vessel walls has been well documented This article describes
      six cases that exhibited the unusual globular pattern of deposition on light
      microscopy, yet exhibited the classic histochemical and immunohistochemical
      properties of deposited amyloid This deposition pattern is a novel finding in the
      gastrointestinal system. Endoscopic examination of five patients revealed mild
      nodularity of the gastric mucosa and diffuse gastritis. In the other case,
      macroscopic examination of resected small intestine showed focal mucosal
      depressions. In all six cases, light microscopy study revealed round to oval
      shaped globules in the lamina propria, with globule diameters of 3 to 40 microm.
      When stained with Congo red, the deposited material refracted polarised light,
      and immunohistochemical testing showed a positive reaction to AA antibody. The
      deposits did not react with antibodies to beta2 microglobulin, transthyretin, or
      lambda and kappa light-chain immunoglobulins. None of the laboratory or clinical
      findings in the six cases was compatible with monoclonal gammopathy or multiple
      myeloma. The literature contains a few case reports of globular amyloid
      deposition in the liver, but this is the first description of a globular pattern
      in the gastrointestinal tract. The pathogenesis and significance of this finding
      are not clear, and will require further study.

PMID- 12000198
TI  - Ambulatory treatment with intravenous norepinephrine in a patient with end stage
      renal disease and generalized AA amyloidosis.
AB  - A 35-year-old man with juvenile rheumatoid arthritis and generalized AA
      amyloidosis of 10 years duration developed end stage renal failure. Following
      appendectomy, the patient experienced progressive circulatory failure which
      required IV treatment with norepinephrine. All attempts to discontinue IV
      norepinephrine failed, each leading to recurrent life-threatening hypotension.
      Finally, a central venous port with a portable mechanical infusion pump system
      was implanted supplying a continuous norepinephrine infusion. The patient then
      became independently mobile and could be discharged. For three months, the
      patient was monitored as an outpatient and treated by ambulatory intermittent
      hemofiltration. Finally, the patient suffered from a hemorrhagic infarction of
      the small bowel due to postoperative adhesions and died shortly after surgery. At
      autopsy, advanced generalized AA amyloidosis was found. Amyloid deposits had
      almost entirely replaced the cortex and the medulla of the adrenal glands. It can
      be speculated that the requirement of exogenous norepinephrine may be in part due
      to an adrenal insufficiency whereas it was initially considered as being only
      related to cardiac involvement. A continuous ambulatory treatment with
      catecholamines could be a possible treatment - at least temporarily - in amyloid
      cases in which all other attempts have failed to prevent chronic life-threatening
      hypotension.

PMID- 12000199
TI  - IX International Symposium on Amyloidosis, July 15-21, 2001, Budapest, Hungary.

PMID- 12000200
TI  - Does depression hurt?
AB  - Depression is an illness that causes symptoms in both the body and the brain,
      i.e., painful physical as well as emotional and vegetative symptoms. Ascending
      serotonergic and noradrenergic pathways may mediate the emotional and vegetative
      symptoms of depression and can potentially be targets of serotonin and
      norepinephrine reuptake inhibitors to obtain relief of these symptoms. Descending
      serotonergic and noradrenergic pathways may regulate the painful physical
      symptoms of depression, and when targeted by serotonin and norepinephrine
      reuptake inhibitors, relieve these symptoms as well. Selective serotonin reuptake
      inhibitors have a remission rate of 35%, and dual-action reuptake inhibitors have
      a 45% remission rate. Despite these results, the best treatment of depression
      currently recognizes the 3 types of symptoms and targets them all for complete
      remission no matter which drug is used.

PMID- 12000201
TI  - Third generation anticonvulsants in bipolar disorder: a review of efficacy and
      summary of clinical recommendations.
AB  - BACKGROUND: To review the literature on efficacy of third generation
      anticonvulsants for treatment of bipolar disorder and provide clinical
      recommendations. METHOD: Open and controlled studies, case reports, and case
      series on the efficacy of lamotrigine, gabapentin, topiramate, tiagabine, and
      zonisamide were located through electronic searches of several databases, by
      manual search of proceedings of international meetings, and through contacting
      authors of recent reports. RESULTS: Lamotrigine is the best studied
      anticonvulsant and has efficacy in acute bipolar depression and in longer term
      treatment of bipolar depression as well as rapid-cycling bipolar II disorder but
      not in acute mania. Open reports suggest usefulness of gabapentin as an adjunct
      in bipolar disorder, but double-blind trials failed to confirm efficacy in acute
      mania and treatment-resistant rapid-cycling bipolar disorder. Topiramate is
      reported to be effective in acute mania and rapid-cycling bipolar disorder in
      several open studies, but methodological problems in a double-blind study led to
      a failed study in acute mania. However, topiramate may lead to weight loss in
      some patients. Zonisamide deserves further investigation, but tiagabine does not
      appear to be useful in acute mania. CONCLUSION: Lamotrigine clearly fills an
      unmet need in treating bipolar depression and rapid-cycling bipolar disorder.
      Other third generation anticonvulsants with the exception of tiagabine offer
      promise but require confirmation of their efficacy from double-blind studies.

PMID- 12000202
TI  - Effect of reboxetine on depression in Parkinson's disease patients.
AB  - BACKGROUND: Depression occurs frequently in patients with Parkinson's disease and
      appears to be associated with increased disability and reduced quality of life.
      Pharmacologic treatment with tricyclic antidepressants or serotonin reuptake
      inhibitors may produce adverse effects on cognition or motor functions in
      Parkinson's disease patients. The efficacy of reboxetine, a novel norepinephrine
      reuptake inhibitor, has been shown in major depressive disorder, with specific
      effects on motivation and negligible effects on psychomotor and cognitive
      function. METHOD: The effects of reboxetine on depression were investigated in 16
      patients with idiopathic Parkinson's disease in an open, prospective study. Prior
      antidepressant medication was stopped because of lack of efficacy or intolerable
      side effects. Severity of depressive symptoms was assessed by the Hamilton Rating
      Scale for Depression, the Self-Rating Depression Scale, the Snaith-Hamilton
      Pleasure Scale, and the Social Adaptation Self-Evaluation Scale during the study
      period of 4 weeks. RESULTS: A significant improvement in depression scores was
      observed after 4 weeks (z = -3.31, p < .008). In 1 subject, reboxetine treatment
      was discontinued because of psychotic symptoms. Seven patients experienced
      transient side effects, including restlessness, insomnia, and increased sweating.
      There were no significant changes in parkinsonian motor symptoms or dosage of
      levodopa. CONCLUSION: Reboxetine appears to be effective and well tolerated in
      Parkinson's disease patients receiving 4 weeks of treatment of moderate-to-severe
      depression. There are good theoretical and clinical reasons, including
      pharmacologic specificity of effects and low incidence of side effects, to
      consider reboxetine for treatment of depression in Parkinson's disease.

PMID- 12000203
TI  - Somatic symptoms, depression, and antidepressant treatment.

PMID- 12000204
TI  - Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double
      blind placebo-controlled trial.
AB  - BACKGROUND: Despite treatment advances, major depressive disorder (MDD) is still
      a significant cause of morbidity and mortality. Current therapies frequently fall
      short of providing full remission. In addition, physical symptoms are commonly
      seen in MDD patients, increasing overall morbidity and health care utilization.
      Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and
      norepinephrine, was evaluated for efficacy and tolerability/safety in the
      treatment of MDD and associated physical symptoms. METHOD: In this multicenter,
      double-blind, parallel-group study, adult patients with DSM-IV MDD were randomly
      assigned to receive placebo (N = 122) or duloxetine (60 mg/day, N = 123) for 9
      weeks. The primary efficacy measure was the 17-item Hamilton Rating Scale for
      Depression (HAM-D-17) total score. Painful physical symptoms were assessed using
      visual analog scales, and global illness and quality of life were evaluated using
      the Clinical Global Impressions-Severity scale, the Patient Global Impressions
      Improvement scale, and the Quality of Life in Depression Scale. Safety and
      tolerability were determined by monitoring discontinuation rates, adverse events,
      vital signs, and laboratory results. RESULTS: Duloxetine was significantly
      superior to placebo (p < .001) in reducing HAM-D-17 total scores, starting at
      week 2. The estimated probability of remission for duloxetine-treated patients
      (44%) was almost 3 times that of placebo patients (16%). Duloxetine significantly
      reduced painful physical symptoms in comparison with placebo. Discontinuation due
      to adverse events for duloxetine-treated patients (13.8%) compared favorably with
      the rates reported for SSRIs in other studies. Nausea, dry mouth, and somnolence
      were the most common adverse events; no significant incidence of hypertension was
      seen. CONCLUSION: Duloxetine, 60 mg/day, is a well-tolerated and effective
      treatment for MDD that reduces painful physical symptoms. These findings suggest
      that duloxetine may be a first-line treatment for patients with MDD and
      associated painful physical symptoms.

PMID- 12000205
TI  - Randomized trial of the efficacy of bright-light exposure and aerobic exercise on
      depressive symptoms and serum lipids.
AB  - BACKGROUND: Season-related subsyndromal depressive symptoms during winter are
      common among populations at high latitudes. Both physical exercise and exposure
      to bright light can relieve the fatigue and downturn of mood associated with the
      shortening length of day. Serum cholesterol level may be related to changes in
      mood, but the evidence is contradictory. Our objective was to compare the effect
      of aerobic exercise with or without bright-light exposure on health-related
      quality of life, mood, and serum lipids in a sample of relatively healthy adult
      subjects. METHOD: A randomized controlled trial was conducted with subjects
      allocated to group aerobics training in a gym with bright light (2500-4000 lux)
      (N = 40) or normal illumination (N = 42) or to relaxation/stretching sessions in
      bright light as a control group (N = 42) twice a week for a period of 8 weeks.
      Changes in mood were recorded using questionnaires at the beginning of the study,
      at weeks 4 and 8. and at follow-up 4 months after the study. A blood sample was
      drawn before and after the 8-week intervention to measure the concentrations of
      serum lipids. RESULTS: Ninety-eight subjects completed the 8-week study. Both
      exercise and bright light effectively relieved depressive symptoms. Bright light
      reduced atypical depressive symptoms more than exercise (p = .03), based on the
      atypical symptoms subscore of the Structured Interview Guide for the Hamilton
      Depression Rating Scale-Seasonal Affective Disorders Version Self-Rating Format.
      There were no significant differences between the study groups in the changes in
      serum lipid levels. CONCLUSION: Bright light administered twice a week, alone or
      combined with physical exercise, seems to be a useful intervention for relieving
      seasonal mood slumps.

PMID- 12000206
TI  - Menstrual abnormalities and polycystic ovary syndrome in women taking valproate
      for bipolar mood disorder.
AB  - BACKGROUND: Valproate treatment has been associated with high rates of menstrual
      abnormalities, hyperandrogenism, and polycystic ovaries in women with epilepsy.
      This pilot study investigated whether valproate treatment had the same
      associations in women with bipolar disorder. METHOD: One hundred forty outpatient
      women with a DSM-IV diagnosis of bipolar disorder (aged 15-45 years) were
      surveyed on their medical, psychiatric, and reproductive health history. Thirty
      two women met entry criteria for the study and were divided into 2 groups: (1)
      those currently receiving valproate (valproate, N = 17) and (2) those who were
      not currently taking valproate (nonvalproate, N = 15). These 2 groups were
      compared with a normal (never diagnosed with a psychiatric disorder) control
      group of 22 women. Women in the valproate group with current menstrual problems
      (N = 7) underwent further assessment for the presence of polycystic ovaries and
      hyperandrogenism. RESULTS: The age at onset of menses, mean length of menstrual
      cycle, and mean length of menses were not significantly different between the
      groups. Significantly more women reported menstrual abnormalities in the
      valproate group (47%) than women not receiving valproate (13%) and controls (0%).
      Forty-one percent of women with bipolar disorder taking valproate had polycystic
      ovary syndrome. CONCLUSION: These results suggest high rates of menstrual
      disturbances and polycystic ovary syndrome in women with bipolar disorder
      currently receiving valproate.

PMID- 12000207
TI  - Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients.
AB  - BACKGROUND: Escitalopram is the single isomer responsible for the serotonin
      reuptake inhibition produced by the racemic antidepressant citalopram. The
      present randomized, double-blind, placebo-controlled, fixed-dose multicenter
      trial was designed to evaluate the efficacy and tolerability of escitalopram in
      the treatment of major depressive disorder. METHOD: Outpatients with an ongoing
      DSM-IV major depressive episode (N = 491) were randomly assigned to placebo,
      escitalopram, 10 mg/day, escitalopram, 20 mg/day, or citalopram, 40 mg/day, and
      entered an 8-week double-blind treatment period following a 1-week single-blind
      placebo lead-in. Clinical response was evaluated by the Montgomery-Asberg
      Depression Rating Scale (MADRS), the 24-item Hamilton Rating Scale for Depression
      (HAM-D), the Clinical Global Impressions (CGI) scales, the Hamilton Rating Scale
      for Anxiety (HAM-A), and patient-rated quality-of-life scales. RESULTS:
      Escitalopram, at both doses, produced significant improvement at study endpoint
      relative to placebo on all measures of depression; significant separation of
      escitalopram from placebo was observed within I week of double-blind treatment.
      Citalopram treatment also significantly improved depressive symptomatology
      compared with placebo; however, escitalopram, 10 mg/day, was at least as
      effective as citalopram, 40 mg/day, at endpoint. Anxiety symptoms and quality of
      life were also significantly improved by escitalopram compared with placebo. The
      incidence of discontinuations due to adverse events for the escitalopram 10
      mg/day group was not different from the placebo group (4.2% vs. 2.5%; p = .50),
      and not different for the escitalopram 20 mg/day group and the citalopram 40
      mg/day group (10.4% vs. 8.8%; p = .83). CONCLUSION: Escitalopram, a single isomer
      SSRI, is well-tolerated and has demonstrated antidepressant efficacy at a dose of
      10 mg/day.

PMID- 12000208
TI  - Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled,
      double-blind study.
AB  - BACKGROUND: Mood stabilizers appear to be more potent in treating mania than
      depression. The anticonvulsant lamotrigine has been shown to be effective for
      bipolar depression. This study examines putative antidepressive properties of
      lamotrigine in a mainly unipolar routine clinical patient population. METHOD:
      Forty patients with a depressive episode (DSM-IV criteria) requiring psychiatric
      intervention received lamotrigine or placebo using a fixed dose escalation scheme
      with a target dose of 200 mg/day for 9 weeks. Additionally, all patients were
      treated with paroxetine. Hamilton Rating Scale for Depression (HAM-D) and
      Clinical Global Impressions scale (CGI) ratings were used to monitor therapeutic
      efficacy. RESULTS: Adjunctive treatment with lamotrigine did not result in a
      significant difference in HAM-D total score at the endpoint of the study when
      compared with paroxetine alone. However, lamotrigine demonstrated significant
      efficacy on core depressive symptoms as reflected by HAM-D items 1 (depressed
      mood; p = .0019), 2 (guilt feelings; p = .0011), and 7 (work and interest; p =
      .049) and the CGI-Severity of Illness scale (p < .0001). Patients receiving
      lamotrigine had fewer days on treatment with benzodiazepines and fewer
      withdrawals for treatment failure. Lamotrigine appeared to accelerate the onset
      of action of the antidepressant. Two patients on lamotrigine treatment developed
      neutropenia, and 1 developed a benign rash. There was no detectable
      pharmacokinetic interaction between lamotrigine and paroxetine. CONCLUSION:
      Lamotrigine might have antidepressive properties in unipolar patients and may
      accelerate onset of action when given in combination with typical
      antidepressants.

PMID- 12000209
TI  - Phenylpropanolamine appears not to promote weight loss in patients with
      schizophrenia who have gained weight during clozapine treatment.
AB  - BACKGROUND: Weight gain is a common side effect of clozapine treatment and may
      expose patients to obesity-associated health risks. We proposed that concomitant
      treatment with an appetite suppressant such as phenylpropanolamine (PPA) would
      lead to a decrease in appetite and therefore loss of weight. METHOD: This was a
      12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in
      outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on
      clozapine treatment for at least 4 months and had gained > 10% of their baseline
      body weight since starting clozapine. Patients were evaluated for adverse effects
      and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a
      short dietary quiz, and blood indices were completed monthly. RESULTS: Sixteen
      patients were equally randomly assigned to receive PPA or placebo. The groups did
      not differ in mean age, baseline weight, dose of clozapine, baseline PANSS
      scores, or the percent of weight gained since the start of clozapine. There was
      no significant effect of treatment on weight (t = 0.219, df = 10, p = .831).
      There was no significant change in either the total PANSS scores (t = -0.755, df
      = 10, p = .468), the positive or negative symptom cluster scores, or any of the
      remaining variables. CONCLUSION: Phenylpropanolamine 75 mg/day was well tolerated
      but was not effective in reversing established weight gain associated with
      clozapine treatment in stable outpatients with schizophrenia.

PMID- 12000210
TI  - An open-label study of naltrexone in the treatment of kleptomania.
AB  - BACKGROUND: The present study was designed to test the short-term efficacy and
      safety of naltrexone in the treatment of kleptomania. METHOD: 10 subjects (7
      women, 3 men) who fulfilled DSM-IV criteria for kleptomania and were free from
      other Axis I diagnoses by the Structured Clinical Interview for DSM-IV screening
      participated in a 12-week naltrexone open-label trial. Kleptomania symptom change
      was assessed with the Clinical Global Impressions scale (both severity and
      improvement measures), Sheehan Disability Scale (SDS), Global Assessment of
      Functioning (GAF), and Kleptomania Symptom Assessment Scale. Side effects were
      monitored weekly, and liver function tests were administered every 2 weeks.
      RESULTS: Naltrexone reduced urges to steal and stealing behavior. Subjects showed
      significant improvement (p < .005) over the 11-week treatment period in all
      measures compared with measures taken at baseline. Seven subjects (70.0%) were
      very much improved and 2 (20.0%) were much improved at study end. Subjects also
      reported overall significant improvement in social and occupational functioning
      as determined by both the GAF and the SDS (p < .000). Men responded to naltrexone
      as well as women. The mean naltrexone dose required for effective symptom control
      was 145 mg/day. Nausea was common during the first week of treatment. Five
      subjects (50.0%) reported previous trials of medication and cognitive-behavioral
      therapy without any effect on kleptomania symptoms. CONCLUSION: The present
      findings provide evidence that naltrexone may be effective in the treatment of
      kleptomania. The present report is preliminary. Further studies are needed to
      confirm these findings.

PMID- 12000211
TI  - Prevalence of sexual dysfunction among newer antidepressants.
AB  - BACKGROUND: Sexual dysfunction commonly occurs during antidepressant treatment.
      However, the reported rates of sexual dysfunction vary across antidepressants and
      are typically underreported in product literature. The objectives of this study
      were (1) to estimate the prevalence of sexual dysfunction among patients taking
      newer antidepressants (bupropion immediate release [IR], bupropion sustained
      release [SR], citalopram, fluoxetine, mirtazapine, nefazodone, paroxetine,
      sertraline, venlafaxine, and venlafaxine extended release [XR]) and (2) to
      compare physician-perceived with patient-reported prevalence rates of
      antidepressant-associated sexual dysfunction. METHOD: This cross-sectional,
      observational study was conducted in 1101 U.S. primary care clinics. Adult
      outpatients (4534 women and 1763 men) receiving antidepressant monotherapy were
      enrolled. The prevalence of sexual dysfunction was measured using the Changes in
      Sexual Functioning Questionnaire. RESULTS: In the overall population, bupropion
      IR (22%) and SR (25%) and nefazodone (28%) were associated with the lowest risk
      for sexual dysfunction, whereas selective serotonin reuptake inhibitor (SSRI)
      antidepressants, mirtazapine, and venlafaxine XR were associated with higher
      rates (36%-43%). In a prospectively defined subpopulation unlikely to have
      predisposing factors for sexual dysfunction, the prevalence of sexual dysfunction
      ranged from 7% to 30%, with the odds of having sexual dysfunction 4 to 6 times
      greater with SSRIs or venlafaxine XR than with bupropion SR. Physicians
      consistently underestimated the prevalence of antidepressant-associated sexual
      dysfunction. CONCLUSION: Ours is the first study to assess sexual dysfunction
      across the newer antidepressants using consistent methodology and a validated
      rating scale. Overall, SSRIs and venlafaxine XR were associated with higher rates
      of sexual dysfunction than bupropion or nefazodone. Because antidepressant
      associated sexual dysfunction is considerably underestimated by physicians,
      greater recognition and education are imperative when prescribing antidepressant
      treatment.

PMID- 12000212
TI  - Combined antidepressant treatment: a risk factor for switching in bipolar
      patients.

PMID- 12000213
TI  - Palinopsia and paroxetine withdrawal.

PMID- 12000214
TI  - Smoking in bipolar and schizophrenic patients.

PMID- 12000215
TI  - Sleep apnea associated with antipsychotic-induced obesity.

PMID- 12000216
TI  - Synergistic effects induced by cycloprodigiosin hydrochloride and epirubicin on
      human breast cancer cells.
AB  - The effects of cPrG x HCl and epirubicin on the suppression of cell growth were
      examined on human breast cancer cell line (MDA-MB-231). Either cPrG x HCl or
      epirubicin alone showed a tumor growth inhibition in a time- and dose-dependent
      manner, however, the combinatory use of cPrG x HCl together with epirubicin
      resulted in prominent synergistic effects on the breast cancer cells. In the in
      vitro studies, the combinatory use of these two drugs accelerated apoptotic cell
      death as revealed by morphological changes as well as by the appearance of subG1
      population by flow cytometry. In addition, confocal microscopy revealed that the
      accumulation of epirubicin in nucleus increased apparently when cPrG x HCl were
      present. In the in vivo assay, nude mice bearing xenografted tumor cells received
      4 weeks of intraperitoneal administration of cPrG-HCl and epirubicin. After 12
      days, the combinatory treatment significantly suppressed the tumor growth
      compared to the controls. The TUNEL staining revealed that tumor cells in cPrG x
      HCl plus epirubicin-treated mice exhibited a higher apoptotic rate. In addition,
      31P-NMR studies on the xenografted tumor revealed that cPrG x HCl lowered tumor
      pHi (below pH 6.9). while it did not affected muscle pHi. No pathological changes
      were observed in any intrinsic organs and the serum alanine aminotransferase
      levels remained within normal limits among the groups. These results suggest that
      the combinatory use of cPrG x HCl and epirubicin may be useful for breast cancer
      therapy.

PMID- 12000217
TI  - Cholinesterase activity and acetylcholinesterase glycosylation are altered in
      human breast cancer.
AB  - Increasing evidence supports the involvement of cholinesterases in tumorigenesis.
      Several tumour cells show ChE activity, while the acetyl- (AChE) and
      butyrylcholinesterase (BuChE) genes are amplified in leukemias, ovarian carcinoma
      and other cancers. ChE activity was measured in 31 samples of tumoral breast (TB)
      and 20 of normal breast (NB). Despite the wide variations observed, BuChE
      predominated over AChE both in TB and NB. The mean AChE activity in NB was 1.61
      nmol of the substrate hydrolysed per minute and per miligram protein (mU/mg),
      which rose to 3.09 mU/mg in TB (p = 0.041). The BuChE activity dropped from 5.24
      mU/mg in NB to 3.39 mU/mg in TB (p = 0.002). Glycolipid-linked AChE dimers and
      monomers and hydrophilic BuChE tetramers and monomers were identified in NB and
      TB, and their proportions were unmodified by the neoplasia. The amount of AChE
      forms reacting with wheat germ agglutinin (WGA) decreased in TB while that of
      BuChE species was unaffected, demonstrating that the glycosylation of AChE was
      altered in TB. The binding of AChE and BuChE with antibodies was unaffected by
      the neoplasia. The difference in lectin reactivity between erythrocyte and breast
      AChE, the lack of AChE in blood plasma, and the finding of monomeric BuChE in
      breast but not in plasma suggest that breast epithelial cells produce AChE for
      membrane attachment and hydrophilic BuChE for secretion. Several reasons are
      provided to explain the altered expression of ChEs in breast cancer.

PMID- 12000218
TI  - Survival of women after breast conserving surgery for early stage breast cancer.
AB  - BACKGROUND: Increasing numbers of older women with breast cancer are receiving
      breast-conserving surgery (BCS). However, substantial numbers of them are not
      receiving either axillary dissection or adjuvant irradiation. OBJECTIVE: To
      determine whether failure to perform axillary dissection or irradiation is
      associated with decreased survival in women with early-stage breast cancer.
      METHOD: We studied 26,290 women aged > or = 25 in 1988-1993 from the
      surveillance, epidemiology, and end results (SEER) data and 5,328 women aged > or
      = 65 in 1991-1993 from SEER-Medicare linked data, who had early-stage breast
      cancer and received BCS. RESULTS: Twenty seven percent of women aged > or = 25
      receiving BCS did not receive axillary dissection, most of whom (74%) were age >
      or = 65. Women receiving BCS with axillary dissection had lower 7-year breast
      cancer-specific mortality than did those without dissection (hazard ratio = 0.53,
      95% confidence interval: 0.44-0.63). We found an interaction between receipt of
      axillary dissection and radiotherapy on survival of older women after BCS. Women
      who received either axillary dissection or radiotherapy experienced similar
      survivals to those who received both axillary dissection and radiation, while
      women who received neither treatment experienced poorer survival (hazard ratio =
      1.76, 1.23-2.52), after controlling for demographics, tumor size and comorbidity.
      CONCLUSIONS: Women who receive neither axillary dissection nor radiation therapy
      after BCS experience an increased risk of death from breast cancer. The lack of
      improvement in the past two decades in survival of older women with breast cancer
      may be explained in part by the increasing use of treatments that do not address
      potential tumor in axillary nodes.

PMID- 12000219
TI  - Enhancement of radiosensitivity of the MCF-7 breast cancer cell line with human
      chorionic gonadotropin.
AB  - Secretion of human chorionic gonadotropin (hCG) during pregnancy induces
      differentiation of the mammary gland, thereby making breast tissue less
      susceptible to carcinogenesis. HCG binds to specific hCG receptors on mammary
      epithelial cells inducing changes in gene expression that can inhibit cell
      proliferation and, therefore, interfere with tumorigenesis. Since breast cancer
      cells also contain a relatively high level of the hCG receptor, hCG has potential
      as a therapeutic agent. We postulated that hCG might also enhance the
      radiosensitivity of breast cancer cells and, therefore, be useful as an
      adjunctive therapy. In the present study, MCF-7 breast cancer cells grown in cell
      culture were treated with hCG (0.2-5 IU/ml) for 24 h prior to exposing the cells
      to 0 Gy, 3 Gy, 4 Gy, or 5 Gy of radiation. Following irradiation, the MCF-7 cells
      were incubated either in the presence or absence of hCG. Cell survival was
      monitored with an MTT assay 1 day, 4 days, and 7 days after irradiation. All of
      the concentrations of hCG tested enhanced radiosensitivity of MCF-7 cells. The
      maximum enhancement occurred with MCF-7 cells that had been exposed to 2 IU/ml of
      hCG for at least 24 h prior to irradiation with 4 Gy. The use of higher
      concentrations of hCG or a higher dose of radiation did not increase the
      enhancement effect. Treatment of MCF-7 cells with hCG for only 24 h was
      sufficient to achieve the maximum effect. However, maintaining the cells in hCG
      beyond 24 h increased the effectiveness of the lowest hCG concentration. Using a
      linear-quadratic equation to analyze the data, we determined that the use of hCG
      would result in an 8-10% reduction in MCF-7 cell survival at a dose of 2 Gy, a
      typical dose used in conventional cancer therapy.

PMID- 12000220
TI  - Staging of breast cancer: new recommended standard procedure.
AB  - BACKGROUND: Staging procedures used to detect metastatic breast cancer at the
      time of diagnosis are bone scan (BS), chest X-ray (CXR), liver ultrasonography
      (LUS) and laboratory parameters (LP). These procedures are expensive and not all
      patients need them. We aimed to identify groups of patients with different risks
      for metastatic disease. METHODS: We reviewed data from 1,218 consecutive cases of
      breast cancer. Pathological and biological parameters and instrumental procedures
      performed at the time of diagnosis and during 6 months of follow-up were
      recorded. True positive and negative, false positive and negative cases were
      evaluated. All cases were grouped on the basis of tumour size, nodal involvement,
      biological characteristics, menopausal status and age. RESULTS: We observed 46
      (3.8%) true positive cases with metastatic disease at the time of diagnosis.
      Documentation relating to BS, CXR and LUS was available for 1,193, 1,206 and
      1,206 patients, respectively, with 37 (3.1%), 8 (0.7%) and 10 (0.8%) true
      positive tests. Logistic regression analysis showed significant odds ratio
      estimates for pT status and nodal status, thus highlighting the role of these
      morphological data. These findings suggest that breast cancer patients can be
      divided into two subgroups: first group pT1-3N0-1. with < or = 3 involved nodes,
      and second group pT1-3N1 with > or = 4 involved nodes, pT4 and pN2 (metastases
      detection rate 1.46 and 10.68%, respectively). In the former group the
      appropriate procedures of staging would only be laboratory parameters, whereas in
      the latter group BS, CXR, LUS, LP and tumour markers CEA and CA 15.3 would.be
      necessary. CONCLUSIONS: The standard staging procedures to detect metastatic
      disease at breast cancer diagnosis require modification. On the basis of the
      literature data and our findings, the full staging procedure is appropriate in
      the second group of patients.

PMID- 12000221
TI  - MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is
      differentially regulated by stromal-epithelial interactions.
AB  - Tissue remodeling is a key element in the local invasion and metastasis of
      malignant breast tumors. The degradation of extracellular matrix that is
      associated with this process is thought to be mediated by a number of Zn2+
      dependent matrix metalloproteinases (MMPs). In most cases these enzymes are not
      produced by the malignant epithelium itself but by adjacent breast stroma,
      suggesting an important role for cell-cell interactions. We have analyzed
      Gelatinase A (MMP-2) and Gelatinase B (MMP-9) gene expression in a panel of six
      breast cancer cell lines and six primary cultures of stromal cells deriving from
      breast cancer biopsies. With one exception we did not detect MMP-2 or MMP-9 gene
      expression in any of the established tumor cell lines. Conversely, tumor stroma
      derived fibroblasts expressed MMP-2 mRNA. although no MMP-9 mRNA was seen in
      RNase protection assays. When fibroblasts were cultured in the presence of media
      conditioned by MCF-7 tumor cells, MMP-2 enzyme production increased but MMP-9
      activity remained undetectable. However, when fibroblasts and MCF-7 tumor cells
      were co-cultured together, MMP-9 was induced. These observations were confirmed
      by immunocytochemical analysis of co-cultures of MCF-7 and tumor-derived
      fibroblasts in which MMP-2 and MMP-9 protein expression was confined to stromal
      cells adjacent to MCF-7 tumor cells. No MMP-2 or MMP-9 staining was detected in
      monocultures of the two respective cell types. We conclude that MMP-2 expression
      is present in the stroma of malignant tumors and is increased by paracrine
      stimulation mediated by soluble factors. In contrast, MMP-9 expression tumor
      derived fibroblasts requires direct contact with malignant tumor epithelium.

PMID- 12000222
TI  - Retinoic acid receptor beta2 inhibition of metastasis in mouse mammary gland
      xenografts.
AB  - The retinoic acid receptor beta2 (RARbeta2) protein is a putative tumor
      suppressor that inhibits proliferation and can induce apoptosis when introduced
      into breast, cervical, lung, and pancreatic cancer cell lines. To determine if
      RARbeta2 suppresses proliferation of mammary-derived cancer cells in vivo, we
      transduced MDA-MB-435 breast cancer cells with the LXSN retroviral vector
      containing RARbeta2 and implanted LXSN vector- or RARbeta2-transduced cells into
      the mammary fat pads of nude and severe combined immune deficiency (SCID) mice.
      We analyzed the xenografts for several tumor parameters, including tumor size,
      inflammation, vascularity, mitoses, tumor recurrence at the primary site
      following resection, and metastases. We found that 19 of 52 mice inoculated with
      vector-transduced cells developed metastases in multiple organs while only one of
      55 mice receiving RARbeta2-transduced cells displayed evidence of metastases (p <
      0.000001, combined experiments, two-tailed Fisher's exact test). Moreover,
      RARbeta2-tumor cell recipient mice had a lower incidence of post-resection tumor
      recurrence (8/55 vs. 25/52, p = 0.0004), 34% less necrosis (in three of four
      experiments, p = 0.001), and 39% fewer mitoses in tumor tissue (p < 0.000001).
      Our findings suggest that RARbeta2 may play a role in inhibiting the metastatic
      cascade in a mouse mammary gland xenograft tumor model and is a potential
      candidate for therapeutic intervention in human breast cancer.

PMID- 12000223
TI  - Selenium reduces hemoglobin-induced epithelial damage to intestinal mucosa.
AB  - Modified hemoglobins are being considered as possible "blood substitutes."
      Experiments were performed to determine whether diaspirin cross-linked hemoglobin
      (DBBF-Hb) produces epithelial damage and whether this is reduced by selenium
      (Se). Anesthetized Sprague-Dawley rats, half of which received 2 x 10(-6) g/ml
      Se, daily for 3 weeks, in their drinking water, were injected with a 5 ml bolus
      of 10 mg/ml DBBF-Hb. Control animals received saline (5 animals per group). After
      30 minutes, the intestine was perfusion-fixed for light and electron microscopy.
      Eighty villi per rat were assigned an epithelial integrity index (E.I.), ranging
      from 1 (intact) to 3 (some cell-cell and cell-basement membrane separation). In
      non-Se rats, E.I. was significantly compromised by DBBF-Hb, compared to HBS-BSA
      (2.47+/-0.57 (SD) vs. 1.36+/-0.49, p<0.001). In Se rats, neither injection with
      DBBF-Hb or HBS-BSA caused epithelial damage (1.03+/-0.17 vs. 1.07+/-0.26). Mast
      cell degranulation per villus (MCD) was measured in 60 villi per rat. In non-Se
      rats, MCD was significantly greater after DBBF-Hb than after HBS-BSA injection
      (1.83+/-1.42 vs. 0.2+/-0.4). Supplementary Se did not reduce this effect. In
      fact, MCD was significantly increased in both sets of rats compared to their non
      Se counterparts (3.27+/-2.40 and 1.48+/-1.70 for DBBF-Hb and HBS-BSA,
      respectively). Since mast cell mediators damage cells, Se must protect the
      mucosal epithelium in some way.

PMID- 12000224
TI  - Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without
      causing blood-brain barrier disruption or brain edema in a rat model of transient
      global brain ischemia-reperfusion.
AB  - In strokes, myocardial infarctions, severe sustained hemorrhagic shock, and donor
      organs, inadequate blood supply results in lack of oxygen to the tissue
      (ischemia). If ischemia is sustained, reperfusion with the needed oxygen can
      result in tissue injury (ischemia-reperfusion injury) due to formation of
      reactive oxygen species. We are studying an oxygen-carrying solution with
      anitoxidant activity formed by cross-linking hemoglobin, superoxide dismutase,
      and catalase to form PolyHb-SOD-CAT. The present report studies its effect on the
      blood-brain barrier and cerebral edema when used in a transient global brain
      ischemia-reperfusion rat model. We compare this solution to sham-control,
      oxygenated saline, stroma-free hemoglobin (SF-Hb), polymerized hemoglobin
      (PolyHb), and a mixture of SF-Hb, SOD, and CAT in free solution. The results show
      that the cross-linked PolyHb-SOD-CAT solution, unlike the other solutions, can
      supply oxygen to ischemic tissues without causing reperfusion injury in the
      transient global brain ischemia-reperfusion model.

PMID- 12000225
TI  - Role of redox potential of hemoglobin-based oxygen carriers on methemoglobin
      reduction by plasma components.
AB  - A functional requirement for all hemoglobin-based oxygen carriers (HBOCs) is the
      maintenance of the heme-iron in the reduced state. This is necessary for the
      reversible binding/release of molecular oxygen and minimization of methemoglobin
      (Fe+3) formation. Acellular hemoglobins are especially susceptible to oxidation
      and denaturation. In the absence of the intrinsic reducing systems of the red
      blood cell, the reduced heme-Fe+2 can be oxidized to form increasing levels of
      methemoglobin that can give rise to free radicals and oxidative cellular damage.
      If acellular HBOCs are to be utilized as red cell substitutes for oxygen
      delivery, these carriers must be stabilized in the plasma, the carrier medium.
      Normal plasma contains reducing components, such as ascorbic acid and
      glutathione, that can afford protection to these acellular HBOCs through electron
      transfer mediated processes. For these components to provide effective reduction
      to an HBOC, a favorable reduction potential difference must exist between the
      reducing agent and the HBOC. Using a modified thin-layer spectroelectrochemical
      method, a determination of the formal reduction potential (vs. Ag/AgCl) of
      several oxygen carriers, including monomeric myoglobin, tetrameric HbA and HbS,
      chemically cross-linked HbXL99alpha, polymerized oxyglobin (FDA approved for
      canine anemia), and the natural cross-linked polymeric Lumbricus hemoglobin, have
      been determined. In contrast to the negative formal reduction potentials (-155 to
      -50 mV) obtained for Mb, HbA, HbS, HbXL99alpha, and oxyglobin, Lumbricus
      hemoglobin exhibited a positive formal reduction potential (approximately 100
      mV). These results may help explain the greater effectiveness of the tested
      reducing agents to reduce met Lumbricus hemoglobin, compared to the other HBOCs,
      back to the required reduced form necessary for physiological binding/release of
      oxygen. Each reducing agent was capable of reducing met Lumbricus hemoglobin to
      the fully reduced state, although the kinetics of these reactions were different.
      HbA, HbXL99alpha, and oxyglobin were only partially reduced (10 to 37%) by
      glutathione, beta-NADH, and ascorbic acid under similar conditions.

PMID- 12000226
TI  - In vitro study of a novel low-density lipoprotein adsorbent.

PMID- 12000227
TI  - Metabolic responses of cultured cells to oxygenated perfluorocarbon.
AB  - Protoplast-derived cells of albino Petunia hybrida cv. Comanche were used as a
      model, nonphotosynthetic, eukaryotic plant system to study changes in (1) the
      rate of oxygen consumption as measured by a Clark-type oxygen microelectrode, (2)
      mitochondrial membrane potential (MMP) as assessed by Rhodamine 123 fluorescence,
      and (3) intracellular activities of superoxide dismutases (SOD, EC 1.15.1.1) and
      catalases (CAT, EC 1.11.1.6), following culture for up to 14 d in aqueous
      nutrient medium overlaying oxygen-gassed perfluorodecalin (Flutec PP5; F2
      Chemicals, Preston, UK). The mean (+/- s.e.m., n = 7) rate of oxygen consumption
      of Petunia cells after 24 h of culture in the presence of oxygenated PFC was 14.3
      +/- 1.6 mol O2 ml(-1) min(-1), compared to 9.7 +/- 0.8 micromol O2 ml(-1) min(-1)
      for untreated (control) cells (P < 0.05). Similarly, the culture of cells with
      oxygenated PFC for 24 h resulted in a significant (P < 0.05) increase of over 50%
      in the mean MMP, compared to the control. Culture of protoplasts with oxygenated
      PFC also produced significant (P < 0.05) increases in both mean SOD and CAT
      activities after 3-7 d of culture, the former comparable to that reported
      previously for protoplasts of Salpiglossis sinuata cultured with oxygenated PFC.

PMID- 12000228
TI  - In vitro study of urease/AlaDH enzyme system encapsulated into human erythrocytes
      and research into its medical applications.
AB  - In our system, urease/AlaDH have been encapsulated within erythrocytes by using
      slow dialysis methods. Urea is decomposed into ammonia and bicarbonate and the
      ammonia released is converted into alanine by reacting pyruvate under the
      catalytic action of AlaDH. It is very important for our that products are formed
      quickly but the ammonia is not connected definetely. For this aim, urease/AlaDH
      we encapsulated using different enzyme activity ratio (0.5:1.5; 0.5:2.5;
      0.25:1.25 U/U urease/AlaDH). The activities of enzyme systems, encapsulation
      yield, McV, McH, and McHc were measured for each sample. Investigated results
      suggest that loaded enzyme systems can be used as potential carrier systems for
      the removal of high levels of urea from blood.

PMID- 12000229
TI  - Reasons for not using condoms among female sex workers in Indonesia.
AB  - The aim of this study was to gather data on condom use among brothel-based female
      sex workers in Indonesia and to study the reasons for not using condoms in order
      to provide new and existing condom promotion programs with information to improve
      their performance. Quantitative data were gathered by KABP surveys (n = 1450) and
      a condom diary with a sample of 204 female sex workers. Qualitative data were
      collected by conducting focus group discussions and in-depth interviews among
      female sex workers and pimps. Around 53% of sexual intercourses were reported to
      be protected, and 12% of these protected intercourses were preceded by clients'
      argumentation against it. Only 5.8% of sex workers consistently used condoms for
      a 2-week period of observation, and this figure decreased to 1.4% for a 4-week
      period. Reasons for not using condoms from the clients' side, as mentioned by the
      sex workers, were perceived less pleasure due to the condom and the belief that
      clients that are acquainted with the sex workers do not need protection against
      sexually transmitted diseases (STDs) or AIDS. The main reasons of female sex
      workers for not using condoms were the beliefs that boyfriends, native
      Indonesians and healthy-looking clients cannot spread STDs. Another reason stated
      was that sex workers had already taken other preventive measures, like taking
      antibiotics. The research also showed that pimps were not very supportive of
      condom use programs in Indonesia. Condom unacceptability is an important reason
      for not using condoms for both clients and female sex workers, whereas pimps, who
      are in the best position to encourage condom use, unfortunately consider condom
      use as a threat to their business. For the successful introduction of consistent
      condom use, it is necessary to design interventions for both sex workers and
      clients and to provide appropriate educational materials and preferred brands of
      condoms. Also, pimps must be involved in intervention programs.

PMID- 12000230
TI  - HIV prevention services in correctional drug treatment programs: do they change
      risk behaviors?
AB  - This study evaluated receipt of HIV prevention services in correctional substance
      abuse treatment programs and examined their impact on short-term risk behaviors.
      The authors performed a secondary analysis of the National Treatment Improvement
      Evaluation Study (NTIES), a prospective cohort study conducted during 1993 to
      1995. The sample included 1,223 adult non-HIV-positive inmates, enrolled in nine
      correctional substance abuse treatment programs. A composite index modeled after
      the validated Risk Assessment Battery measured HIV risk behavior at treatment
      entry and at 12-month follow-up. Overall, most inmates received HIV prevention
      services while in treatment. Controlling for potential confounders, HIV
      prevention services were significantly associated with reduced risk behavior
      among inmates who were out of custody at follow-up, but no such association was
      observed among those still in custody. This analysis suggests that HIV prevention
      services are beneficial in reducing risk behavior among incarcerated individuals
      whose discharge is expected in the near future.

PMID- 12000231
TI  - Needle exchange: how the meanings ascribed to needles impact exchange practices
      and policies.
AB  - The consistency among needle exchange practices, HIV prevention, harm reduction
      goals, and potential program effectiveness are analyzed. Using a modified
      ethnographic approach, qualitative interviews were conducted with staff (n = 59)
      of needle exchange programs (NEPs; n = 15). Interviews addressed operational
      policies; funding and challenges. An iterative, inductive analytic process was
      used. Differences in exchange practices are traced to differences in how workers
      define needles as objects of "risk" and/or "prevention." The weight accorded to
      each definition has implications for service delivery. Among NEPs that ascribe a
      "risk" meaning, workers enforce a strict one-for-one exchange, encourage clients
      to take fewer needles, and penalize clients. Programs that focus on the
      "prevention" meaning of needles work towards improving access, problem solving
      about proper disposal and do not penalize clients. Operational policies that
      restrict access to sterile equipment or discourage attendance need to be
      reconsidered if HIV prevention goals are to be realized.

PMID- 12000232
TI  - Holding the line with a watchful eye: the impact of perceived parental
      permissiveness and parental monitoring on risky sexual behavior among adolescents
      in psychiatric care.
AB  - Adolescents in psychiatric care are at increased risk of HIV, yet little is known
      about the family factors related to sexual risk taking among these youth. We
      explored whether perceived parental monitoring and perceived parental
      permissiveness were linked to high-risk sexual behavior in 169 ethnically diverse
      urban youth seeking mental health services in Chicago, and we tested whether
      adolescent gender moderated these associations. We evaluated sexual risk taking
      at a global level and for specific risk behaviors (e.g., sex without a condom,
      sex while using drugs and alcohol). Girls reported more risky sex overall than
      boys, and girls were more likely than boys to report having sex without a condom.
      At low levels of parental permissiveness, rates of risky sex among boys and
      girls' did not differ, but at high levels of permissiveness girls reported more
      sexual risk taking than boys, and girls were more likely than boys to report
      having sex while using drugs and alcohol and having sex without a condom.
      Findings highlight the complexity of adolescent sexual behavior and the need for
      multilevel assessment of risk taking. Results suggest that parental monitoring
      and permissiveness are more strongly associated with sexual risk taking in
      troubled girls than troubled boys, and they underscore a need for gender
      sensitive, family-focused HIV-prevention programs.

PMID- 12000233
TI  - A validation and reduced form of the Female Condom Attitudes Scale.
AB  - The Female Condom Attitudes Scale is an instrument comprising five correlated
      factors derived from 15 Likert-scale survey items that measure women's attitudes
      toward the female condom. This scale originated from the 30-item scale of Choi,
      Gregorich, Anderson, Grinstead, and Gomez (2001; manuscript under review).
      Exploratory factor analysis of this scale extracted eight correlated factors.
      Reliability coefficients and confirmatory factor analyses refined the instrument
      by reducing the number of factors to five and halving the number of items. The
      reduced form of the Female Condom Attitudes Scale demonstrated both construct and
      convergent validity by predicting self-reported female condom use behavior. It
      also correlated with self-efficacy to use male condoms, sexual comfort, and
      attitudes toward the male condom. The five factors remaining in the final survey
      instrument were Sexual Pleasure Enhancement, Inconvenience, Improved Prophylaxis,
      Sexual Pleasure Inhibition, and Insertion Reluctance. Implications of these
      findings for basic and applied intervention research are discussed.

PMID- 12000234
TI  - Development and psychometric evaluation of the brief HIV Knowledge Questionnaire.
AB  - This research evaluated the psychometric properties of a brief self-report
      measure of HIV-related knowledge, the 18-item HIV Knowledge Questionnaire (HIV-KQ
      18). Low-income men and women (N = 1,019) responded to 27 items that represented
      the domain of interest. Item analyses indicated that 18 items, with item-total
      correlations ranging from .24 to .57, be retained. Additional analyses
      demonstrated the HIV-KQ-18's internal consistency across samples (alphas = .75
      .89), test-retest stability across several intervals (rs = .76- .94), and strong
      associations with a much longer, previously validated measure (rs = .93-.97).
      Data from three clinical trials indicated that the HIV-KQ-18 detected knowledge
      gains in treated participants when compared to untreated controls. We conclude
      that the HIV-KQ-18 is internally consistent, stable, sensitive to the change
      resulting from intervention, and suitable for use with low-literacy populations.

PMID- 12000235
TI  - Acceptance of HIV testing and counseling among unmarried young adults in Northern
      Thailand.
AB  - A cluster randomized trial was used to assess the effect of an active group
      intervention in promoting utilization of voluntary HIV testing and counseling
      (HIV-TC). Villagers from 40 clusters were sampled to represent the premarital age
      population and assigned into two groups, intervention and comparison. The
      intervention was designed to enhance risk perception and increase knowledge about
      HIV testing. Interviews were performed before and after the intervention. At
      baseline, 23% of 398 participants had been tested for HIV at least once and 90%
      reported testing positive. Most participants perceived that they had no chance of
      being infected with HIV. Among the intervention group, 71% participated in the
      intervention activities. The risk ratio of HIV-TC acceptance among the
      intervention group was 2.92, but the risk difference was only 8.11%. Factors
      associated with HIV-TC acceptance were ever having had a sexually transmitted
      disease, being previously married, intention to get tested, and having partici
      pated in AIDS-related activities.

PMID- 12000236
TI  - Initiation rights.

PMID- 12000237
TI  - Blood-alcohol levels: show me the evidence.

PMID- 12000238
TI  - The good old hockey game.

PMID- 12000239
TI  - The good old hockey game.

PMID- 12000240
TI  - Blood-alcohol levels: show me the evidence.

PMID- 12000241
TI  - Assessing the risks of cervical manipulation for neck pain.

PMID- 12000242
TI  - Assessing the risks of cervical manipulation for neck pain.

PMID- 12000243
TI  - Protestant bioethics.

PMID- 12000244
TI  - Protestant bioethics.

PMID- 12000245
TI  - Accelerated publication versus usual publication in 2 leading medical journals.
AB  - BACKGROUND: A number of medical journals have developed policies for accelerated
      publication of articles judged by the authors, the editors or the peer reviewers
      to be of special importance. However, the validity of these judgements is
      unknown. We therefore compared the importance of articles published on a "fast
      track" with those published in the usual way. METHODS: We identified 12 "case"
      articles--6 articles from the New England Journal of Medicine that were
      prereleased on the journal's Web site before publication in print and 6 "fast
      tracked" articles from The Lancet. We then identified 12 "control" articles
      matched to the case articles according to journal, disease or procedure of focus,
      theme area and year of publication. Forty-two general internists rated the
      articles, using 10-point scales, on dimensions addressing the articles'
      importance, ease of applicability and impact on health outcomes. RESULTS: For
      each dimension, the mean score for the case articles was significantly higher
      than the mean score for the control articles: importance to clinical practice 7.6
      v. 7.1 respectively (p = 0.001), importance from a public health perspective 6.5
      v. 6.0 (p < 0.001), contribution to advancement of medical knowledge 6.2 v. 5.8
      (p < 0.001), ease of applicability in practice 7.0 v. 6.5 (p < 0.001), potential
      impact on health outcomes 6.5 v. 5.9 (p < 0.001). Despite these general findings,
      in 5 of the 12 matched pairs of articles the control article had a higher mean
      score than the case article across all the dimensions. INTERPRETATION: The
      accelerated publication practices of 2 leading medical journals targeted articles
      that, on average, had slightly higher importance scores than similar articles
      published in the usual way. However, our finding of higher importance scores for
      control articles in 5 of the 12 matched pairs shows that current journal
      practices for selecting articles for expedited publication are inconsistent.

PMID- 12000246
TI  - Evaluation of a community-based automated blood pressure measuring device.
AB  - BACKGROUND: Automated devices are widely available in the community for people to
      measure their blood pressure. We assessed the accuracy and reproducibility of a
      brand of community-based automated device against the standard mercury
      sphygmomanometer. METHODS: Same-arm pairs of blood pressure readings were
      obtained with the Vita-Stat 90550 automated device, a sphygmomanometer and the
      Omron HEM-705CP automated device in random order on volunteers in 3 community
      pharmacies using a modified protocol for evaluating blood pressure devices.
      Comparison of readings between the Omron device and the sphygmomanometer served
      as a positive control of how well a laboratory-validated automated device could
      perform in the community. Both the Association for the Advancement of Medical
      Instrumentation (AAMI) and British Hypertension Society (BHS) criteria were used
      to assess the accuracy and reproducibility of readings. RESULTS: The mean blood
      pressure reading and standard error (SE) of the mean for the 108 volunteers (66
      women and 42 men) was 133/77 (SE 2/1) mm Hg with the Vita-Stat device, 131/77 (SE
      2/1) mm Hg with the Omron device and 129/76 (SE 2/1) mm Hg with the
      sphygmomanometer. The mean difference in readings was 4.4/1.0 (standard deviation
      [SD] 9.4/6.2) mm Hg between the Vita-Stat device and the sphygmomanometer and
      1.6/0.6 (SD 9.3/6.4) mm Hg between the Omron device and the sphygmomanometer.
      Neither automated device met the AAMI accuracy criteria for the systolic
      readings. The BHS grades were C/A (systolic unacceptable/diastolic acceptable)
      for each automated device. According to the BHS analytical criterion, all devices
      achieved acceptable reproducibility grades. INTERPRETATION: Neither automated
      device met the AAMI or BHS criteria for accuracy while in use in the community,
      and neither performed as well in the community as in the laboratory.

PMID- 12000247
TI  - A medical early warning system.

PMID- 12000248
TI  - Getting on track: how scientific journals and mainstream journalists could do a
      better job of communicating with the public.

PMID- 12000249
TI  - United Nations Special Session on Children: children's rights under attack.

PMID- 12000250
TI  - CMAJ's new online continuing professional development course.

PMID- 12000251
TI  - Identifying and managing adverse environmental health effects: 2. Outdoor air
      pollution.
AB  - Air pollution contributes to preventable illness and death. Subgroups of patients
      who appear to be more sensitive to the effects of air pollution include young
      children, the elderly and people with existing chronic cardiac and respiratory
      disease such as chronic obstructive pulmonary disease and asthma. It is unclear
      whether air pollution contributes to the development of asthma, but it does
      trigger asthma episodes. Physicians are in a position to identify patients at
      particular risk of health effects from air pollution exposure and to suggest
      timely and appropriate actions that these patients can take to protect
      themselves. A simple tool that uses the CH2OPD2 mnemonic (Community, Home,
      Hobbies, Occupation, Personal habits, Diet and Drugs) can help physicians take
      patients' environmental exposure histories to assess those who may be at risk. As
      public health advocates, physicians contribute to the primary prevention of
      illness and death related to air pollution in the population. In this article we
      review the origins of air pollutants, the pathophysiology of health effects, the
      burden of illness and the clinical implications of smog exposure using the
      illustrative case of an adolescent patient with asthma.

PMID- 12000252
TI  - The appropriate use of carotid endarterectomy.
AB  - For the first 30 years after carotid endarterectomy was first developed,
      anecdotal evidence was used to identify patients with internal carotid artery
      disease for whom this procedure would be appropriate. More recently, the
      appropriateness of carotid endarterectomy for symptomatic patients and
      asymptomatic subjects has emerged from 7 randomized trials. Risk of stroke and
      benefit from the procedure are greatest for symptomatic patients with at least
      70% stenosis of the internal carotid artery. Within this group, carotid
      endarterectomy is most beneficial for the following patients: otherwise healthy
      elderly patients, those with hemispheric transient ischemic attack, those with
      tandem extracranial and intracranial lesions and those without evidence of
      collateral vessels. Risk of perioperative stroke and death is higher in the
      following groups, although they still benefit: patients with widespread
      leukoaraiosis, those with occlusion of the contralateral internal carotid artery
      and those with intraluminal thrombus. Patients with 50% to 69% stenosis
      experience lesser benefit, and some other groups may even be harmed by carotid
      endarterectomy, including women and patients with transient monocular blindness
      only. The procedure is indicated for patients presenting with lacunar stroke and
      for those with a nearly occluded internal carotid artery, but the benefit is
      muted. Patients with less than 50% stenosis do not benefit. In the largest
      randomized trial of asymptomatic subjects, the perioperative risk of stroke and
      death was very low (1.5%), but the results indicated that a prohibitively high
      number of subjects (83) must be treated to prevent one stroke in 2 years. The
      subsequent literature reported higher perioperative risks (2.8% to 5.6%). In
      asymptomatic individuals nearly half of the strokes that occur may be due to
      heart and small-vessel disease. These limitations counter any potential benefit.
      Another trial is in progress and may identify subgroups of asymptomatic subjects
      who would benefit. Meanwhile, most individuals without symptoms fare better with
      medical care.

PMID- 12000253
TI  - Travel warning: Eosinophilic meningitis caused by rat lungworm.

PMID- 12000254
TI  - Antipsychotic clozapine (Clozaril): myocarditis and cardiovascular toxicity.

PMID- 12000255
TI  - Unstable carotid plaque.

PMID- 12000256
TI  - US malpractice premiums soar again.

PMID- 12000257
TI  - MDs still the key to eliminating unfit drivers, jury decides.

PMID- 12000258
TI  - Will bad times ever end for world's poorest children?

PMID- 12000259
TI  - The doctor isn't in (2).

PMID- 12000260
TI  - Romanow's biggest hurdle? Skepticism.

PMID- 12000261
TI  - Stereospecific synthesis of cryptophycin 1.
AB  - [reaction: see text] A brief stereospecific synthesis of cryptophycin 1 is
      described in which (R)-mandelic acid serves as the sole source of asymmetry for
      unit A. The key step is a hetero-Diels-Alder cycloaddition.

PMID- 12000262
TI  - Novel synthesis of 2-arylbenzothiazoles mediated by ceric ammonium nitrate (CAN).
AB  - [reaction: see text] Cyclization of the intermediate radical formed after initial
      oxidative coupling between thiophenols and aromatic nitriles leads to the
      synthesis of a wide range of 2-arylbenzothiazoles.

PMID- 12000263
TI  - Asymmetric deactivation of racemic BINAP-Ru(II) catalysts through complete
      enantiomer discrimination by dimethylbinaphthylamine: highly enantioselective
      hydrogenation of olefin and beta-keto ester.
AB  - [reaction: see text] 3,3'-Dimethyl-2,2'-diamino-1,1'-binaphthyl (DM-DABN) is
      designed as a "chiral poison" (deactivator) for complete enantiomer resolution of
      racemic BINAP-Ru(II) catalysts in a highly enantioselective hydrogenation of beta
      keto ester and kinetic resolution of racemic 2-cyclohexen-1-ol.

PMID- 12000264
TI  - Synthesis and ion conductance behavior of a tetrameric alamethicin ion channel.
AB  - [structure: see text] A porphyrin-tethered construct, containing four full-length
      alamethicin monomers, has been synthesized and characterized. The ion conductance
      data of the assembly in 1 M HCl display long-lived, albeit noisy, channels that
      appear to be voltage-independent multiples of only one conductance state. The
      noise in the data is consistent with the molecular modeling studies, which
      indicate that the side chain of glutamine 7 of alamethicin does not fit well into
      the narrow pore of a parallel four-helix bundle.

PMID- 12000265
TI  - Toward an analogue of the transition state of preD3-D3 isomerization:
      stereoselective synthesis of linearly fused 6-8-6 carbocyclic systems.
AB  - [reaction: see text] A stereoselective synthesis of 6-8-6 fused carbocyclic
      systems based on enol alkylation, ketone allylation, RCM, and Heck cyclization
      was developed to obtain compounds with a carbon framework that mimics the
      putative transition structure of the isomerization of previtamin D3 to vitamin
      D3.

PMID- 12000266
TI  - Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)
      (6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C.
AB  - [reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)
      (6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall
      yield, respectively). Key steps included a tin(II)-mediated aldol followed by a
      syn selective reduction, giving the C7-C9 stereocenters, a second chain extending
      aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common
      gamma-dihydropyrone precursor. We have thus established that synthetic (-)
      (6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)
      (6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.

PMID- 12000267
TI  - Selective ruthenium-catalyzed oxidation of 1,2:4,5-di-O-isopropylidene- beta-D
      fructopyranose and other alcohols with NaOCl.
AB  - [reaction: see text] The asymmetric epoxidation catalyst 1,2:4,5-di-O
      isopropylidene-beta-D-erythro-2,3-hexadiulo-2,6-pyranose 2 was obtained in high
      yield from 1,2:4,5-di-O-isopropylidene-beta-D-fructopyranose 1 via a recyclable
      ruthenium-catalyzed hypochlorite oxidation protocol under biphasic conditions
      (MTBE/water) in the presence of an alkaline buffer (pH 9.5). Other secondary
      alcohols were also oxidized selectively to the corresponding ketones.

PMID- 12000268
TI  - Routine use of natural abundance deuterium NMR in a polypeptidic chiral oriented
      solvent for the determination of the enantiomeric composition of chiral building
      blocks.
AB  - [reaction: see text] Natural abundance deuterium 2D NMR spectroscopy in chiral
      liquid crystal was successfully used to efficiently analyze the enantiomeric
      composition of organic chiral building blocks involved in the syntheses of
      natural and synthetic bioactive products. The results reported here emphasize the
      high potential of this analytical strategy and prove its applicability for
      routinely determining enantiomeric excesses.

PMID- 12000269
TI  - Practical carbonyl-ene reactions of alpha-methylstyrenes with paraformaldehyde
      promoted by a combined system of boron trifluoride and molecular sieves 4A.
AB  - [reaction: see text] A combined system of boron trifluoride and molecular sieves
      is an efficient promoter for the carbonyl-ene reaction of alpha-methylsyrenes
      with paraformaldehyde. The coexistence of BF3 x OEt2 and molecular sieves 4A is
      essential for obtaining high yields of ene products.

PMID- 12000270
TI  - Highly chemoselective rhodium-catalyzed methylenation of fluorine-containing
      ketones.
AB  - [reaction: see text] The rhodium(I)-catalyzed methylenation of functionalized
      fluorinated ketones using trimethylsilyldiazomethane proceeds to give the
      corresponding fluoromethylalkenes in good yields (61-90%). Remarkable
      chemoselectivity was observed for the synthesis of keto-substituted
      organofluorine alkenes.

PMID- 12000271
TI  - Stereochemical anomaly in the thermal conversion of 7,8-dioxy-7
      alkenylbenzocyclobutenes to dihydronaphthalenes.
AB  - [reaction: see text] The stereochemistry of the thermal conversion of
      alkenylbenzocyclobutenol into dihydronaphthalene was studied. Experiments on the
      substrates IV, in which two oxy functions are cis, often resulted in the
      formation of abnormal products in view of the orbital consideration.

PMID- 12000272
TI  - Highly stereoselective ring-opening addition of terminal acetylenes to bicyclic
      olefins catalyzed by nickel complexes.
AB  - [reaction: see text] Treatment of 7-oxa- and 7-azabenzonorbornadienes with
      terminal acetylenes in the presence of Ni(dppe)Cl2, ZnCl2, and Zn powder in
      toluene at 90 degrees C afforded the corresponding cis-2-alkynyl-1,2
      dihydronaphthalene derivatives in moderate to excellent yields with remarkably
      high stereoselectivity.

PMID- 12000273
TI  - Application of tin and nanometer tin in allylation of carbonyl compounds in tap
      water.
AB  - [reaction: see text] Nanometer tin-mediated allylation of aldehydes or ketones in
      distilled or tap water gave rise to corresponding homoallyl alcohol in high yield
      without any other assistance such as heat or supersonic or acidic media.

PMID- 12000274
TI  - Self-assembly of molecular capsules in polar solvents.
AB  - [structure: see text] We present a novel type of molecular capsule formed by self
      organization of calix[4]arenes with several oppositely charged functional groups
      located at their upper rims. In highly polar solvents, the complementary half
      spheres form stable 1:1 complexes with association constants of up to 7 x 10(5)
      M(-)(1) in methanol. The cavity inside the capsules is large enough for the
      inclusion of small aliphatic or (hetero)aromatic guest molecules.

PMID- 12000275
TI  - A copper-free Sonogashira coupling reaction in ionic liquids and its application
      to a microflow system for efficient catalyst recycling.
AB  - [reaction: see text] The PdCl2(PPh3)2-catalyzed Sonogashira coupling reaction, in
      good to high yields, was performed in an ionic liquid ([BMIm][PF6]) in the
      absence of a copper salt. The use of an ionic liquid allows for the facile
      separation and recycling of the catalyst. The application of the above reaction
      in a microflow system in conjunction with an IMM micromixer was also successful.

PMID- 12000276
TI  - An ortho-substituted BIPHEP ligand and its applications in Rh-catalyzed
      hydrogenation of cyclic enamides.
AB  - [reaction: see text] An ortho-substituted BIPHEP ligand, o-Ph-hexaMeO-BIPHEP (1),
      is designed and synthesized. Compared with chiral biaryl phosphines without ortho
      substituents such as BINAP and MeO-BIPHEP, o-Ph-hexaMeO-BIPHEP shows higher
      enantioselectivities in Rh-catalyzed hydrogenation of cyclic enamides.

PMID- 12000277
TI  - Relative and absolute stereochemistry of the didemnaketals, metabolites of a
      Palauan ascidian, Didemnum sp.
AB  - [structure: see text] The absolute stereochemistry of the heptaprenoids
      didemnaketals B (2) and C (3), isolated from a Palauan ascidian, was determined
      using a combination of degradation and derivatization experiments, chiral shift
      methods, and comparison of fragments to known compounds.

PMID- 12000278
TI  - Synthesis and nonlinear optical properties of 1,3,5-methoxy-2,4,6
      tris(styryl)benzene derivatives.
AB  - [reaction: see text] Novel two-dimensional octupoles containing donors at the
      core and acceptors at the edge of peripheral groups were synthesized by Horner
      Wittig reactions. These chromophores show very large first hyperpolarizability
      and good thermal stability and are attractive candidates for nonlinear optical
      materials.

PMID- 12000279
TI  - Facile and regioselective synthesis of phenylpropanoid-substituted flavan-3-ols.
AB  - [reaction: see text] A highly efficient, facile, one-pot regioselective synthesis
      of a series of phenylpropanoid-substituted flavan-3-ols is described. The
      mechanism involves dienone-phenol rearrangement followed by a Michael-type
      reaction.

PMID- 12000280
TI  - Synergistic catalysis of anthrone Diels-Alder reactions.
AB  - [reaction: see text] The combination of an amine base and Lewis acid (Li+) leads
      to synergistic catalysis of the Diels-Alder reaction of anthrone with methyl
      crotonate and some other less reactive dienophiles. These cycloadditions either
      do not occur with the individual catalysts used separately or they are greatly
      accelerated by the combined catalysts. DMSO solvent allows the use of LiCl as the
      Lewis acid source and can provide greater control of subsequent conversion to
      Michael adduct.

PMID- 12000281
TI  - Synthesis of alkaloid 223A and a structural revision.
AB  - [structure: see text] Synthesis of alkaloid 223A has been achieved by sequential
      use of our original conjugate addition reaction to enaminoesters as the key step.
      The proposed structure for natural 223A (A, absolute configuration unknown) was
      revised to B, and the relative stereostructure was determined to be
      5R*,6R*,8R*,9S* by the present synthesis.

PMID- 12000282
TI  - Synthesis of D-erythro-dihydrosphingosine and D-xylo-phytosphingosine from a
      serine-derived 1,5-dioxaspiro[3.2]hexane template.
AB  - [reaction: see text] A serine-derived 1,5-dioxaspiro[3.2]hexane template is shown
      to be a useful precursor for both aminodiol and aminotriol sphingoid bases by its
      conversion to D-erythro-dihydrosphingosine and D-xylo-phytoshingosine.

PMID- 12000283
TI  - First enantioselective total synthesis of (-)-Centrolobine.
AB  - [structure: see text] The first enantioselective total synthesis of (-)
      Centrolobine is described. The key reaction is the synthesis of the cis
      disubstituted tetrahydropyran framework by intramolecular cyclization of the
      enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction
      of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute
      configuration of (-)-Centrolobine is proposed.

PMID- 12000284
TI  - Indium-catalyzed reduction of allyl bromide with gallium or aluminum. Formation
      of allylgallium and allylaluminum sesquibromides.
AB  - [reaction: see text] Fast transmetalation of an allyl group from indium to
      gallium enables the assembly of a catalytic cycle of indium, which accelerates
      the formation of allylgallium sesquibromide. A solution of allylaluminum
      sesquibromide in THF is also prepared from allyl bromide and aluminum metal under
      indium catalysis.

PMID- 12000285
TI  - Enantioselective Diels-Alder reactions with N-hydroxy-N-phenylacrylamide.
AB  - [reaction: see text] The use of hydroxamic acids as templates for Lewis acid
      catalyzed enantioselective Diels-Alder reactions has been examined. A very simple
      chiral Lewis acid, prepared by mixing optically pure binaphthol with 3 equiv of
      trimethylaluminum, catalyzes the [4 + 2] cycloaddition of N-hydroxy-N
      phenylacrylamide with cyclopentadiene at 0 degrees C in high yield (>96%) and
      with a fairly good level of enantioselectivity (91% ee). Facile conversion of the
      products to the corresponding alcohols or aldehydes makes the hydroxamic acid
      intermediates particularly useful.

PMID- 12000286
TI  - N-alkoxyacrylamides as substrates for enantioselective Diels-Alder reactions.
AB  - [reaction: see text] The use of N-alkoxyacrylamides as substrates for Lewis acid
      catalyzed Diels-Alder reactions has been examined. Enantioselectivities up to 92%
      ee have been achieved using very simple chiral Lewis acids prepared from
      triisobutylaluminum and 2,2-dimethyl-alpha,alpha,alpha',alpha'-tetra-1
      naphthalenyl-TADDOL (1-NaphtTADDOL). The use of Yamamoto's Zn-BINOL, easily
      prepared from Et2Zn and 1,1'-bi-2-naphthol (BINOL), proved to be even more
      efficient, and enantioselectivities up to 96% ee were achieved.

PMID- 12000287
TI  - Umpolung strategy for the synthesis of 2-deoxy-C-aryl glycosides: a
      serendipitous, efficient route for C-furanoside analogues.
AB  - [reaction: see text] 2-Deoxy-C-aryl glycosides are potential synthetic targets as
      they form a very vital moiety of several biologically active natural products.
      This paper describes a synthetic route using an umpolung strategy, which has not
      been explored till date. Our synthetic endeavor led to a versatile intermediate
      aryl ketone 10, which has paved the way for two important classes of C
      glycosides, viz., C-alkyl furanosides 12 and methyl 2-deoxy-C-aryl pyranosides
      14.

PMID- 12000288
TI  - Nickel-catalyzed cyclizations and couplings with vinylzirconium reagents.
AB  - [reaction: see text] 1,3-Dienes were prepared by a variety of nickel-catalyzed
      couplings and cyclization processes. Intermolecular or partially intramolecular
      couplings of alkynes, vinylzirconium reagents, and either aldehydes or enones
      efficiently proceeded to generate a broad range of functionalized dienes.

PMID- 12000289
TI  - Studies toward the total synthesis of gymnocin A, a cytotoxic polyether: a highly
      convergent entry to the F-N ring fragment.
AB  - [structure: see text] An efficient and highly convergent synthesis of the
      FGHIJKLMN ring fragment of gymnocin A, a cyctotoxic polycyclic ether isolated
      from the notorious red-tide forming dinoflagellate Gymnodinium mikimotoi, has
      been achieved. The present synthesis relied on extensive use of the B-alkyl
      Suzuki-Miyaura coupling reaction.

PMID- 12000290
TI  - Solid-phase synthesis of 3-alkylamino-1,2,4-triazoles.
AB  - [reaction: see text] A solid-phase synthesis of trisubstituted 3-alkylamino-1,2,4
      triazoles has been developed. The synthesis utilizes immobilized N-acyl-1H
      benzotriazole-1-carboximidamides as key intermediates. Cyclization with
      hydrazines under mild conditions furnishes the title compounds with
      regioselectivity and high purity.

PMID- 12000291
TI  - Rh(I)-catalyzed intramolecular allenic Pauson-Khand reaction: construction of a
      bicyclo[5.3.0]dec-1,7-dien-9-one skeleton.
AB  - [reaction: see text] 1-Phenylsulfonylallenes possessing a hexynyl appendage in
      refluxing toluene in the presence of catalytic amount of rhodium(I) catalyst
      under a carbon monoxide atmosphere underwent regioselective formal [2 + 2 + 1]
      cycloaddition to produce the corresponding bicyclo[5.3.0]dec-1,7-dien-9-one
      derivatives in acceptable yields.

PMID- 12000292
TI  - First direct lithiation of 2-pyridylpiperazine on solid phase.
AB  - [reaction: see text] The first direct lithiation of a pyridine derivative on
      solid phase has been realized. Metalation of polymer-bound 2-pyridylpiperazine
      with the BuLi-LiDMAE reagent followed by electrophilic quenching and subsequent
      cleavage provided a range of new useful C-6 substituted 2-piperazinylpyridines.

PMID- 12000293
TI  - Electrochemical oxidation of N-p-toluenesulfinamides.
AB  - [reaction: see text] Contrasting and interesting electrochemical behavior is
      observed in anodic oxidation of N-substituted p-toluenesulfinamides under
      controlled current conditions. For sulfinamides derived from secondary
      alkylamines and primary arylamines, the N-sulfinyl group is removed and the
      corresponding amines are formed; for sulfinamides derived from primary
      alkylamines, sulfur oxidation yields the corresponding sulfonamides in good
      yields.

PMID- 12000294
TI  - Efficiency of a ruthenium catalyst in metathesis reactions of sulfur-containing
      compounds.
AB  - [reaction: see text] 1,3-Dimesitylimidazol-2-ylidene ruthenium benzylidene
      catalyst (RuCl2(=C(H)Ph)(PCy3)(IMes)) has been successfully employed in ring
      closing metathesis reactions of acyclic diene sulfides, disulfides, and dithianes
      and in self-cross metathesis reactions of ene-sulfides, thioethers, and thiols.

PMID- 12000295
TI  - Enantioselective synthesis of 2-deoxy- and 2,3-dideoxyhexoses.
AB  - [reaction: see text] The enantioselective syntheses of C-6 O-TBS- and N-Cbz
      protected 2-deoxy- and 2,3-dideoxysugars have been achieved in 6-8 steps from
      furfural. A combination of chemo-, regio-, and diastereoselective oxidation and
      reduction reactions produced deoxysugars with various C-6 substitution. A key
      development of this route was the use of o-nitrobenzenesulfonylhydrazide (NBSH)
      as a diimide precursor. These overall procedures allow for the synthesis of eight
      deoxysugars in either enantiomeric form.

PMID- 12000296
TI  - Solid-phase intermolecular radical reactions 2: synthesis of C-glycopeptide
      mimetics via a novel acrylate acceptor.
AB  - [reaction: see text] A novel tetrafluorophenol-linked acrylate is reported as an
      activated acceptor for intermolecular radical reactions. Addition of alkyl
      radicals led to pure products in good yields. We include here the first syntheses
      of C1- and C6-linked glycosides using a solid-phase radical methodology.

PMID- 12000297
TI  - Total Synthesis of (-)-lasubine II by the conjugate addition and intramolecular
      acylation of an amino ester with an acetylenic sulfone.
AB  - [reaction: see text] The conjugate addition of methyl (S)-(2-piperidyl)acetate
      (3) to 2-(3,4-dimethoxyphenyl)-1-(p-toluenesulfonyl)ethyne (4), followed by LDA
      promoted intramolecular acylation, stereoselective reduction, and
      desulfonylation, afforded (-)-lasubine II.

PMID- 12000298
TI  - Ruthenium complex catalyzed direct ortho arylation and alkenylation of aromatic
      imines with organic halides.
AB  - [reaction: see text] The ortho position of the aromatic ring of imino group
      substituted aromatic compounds is directly arylated and alkenylated with organic
      halides in the presence of a catalytic amount of a ruthenium(II)-phosphine
      complex.

PMID- 12000299
TI  - Synthesis of the C(1)-C(18) segment of lophotoxin and pukalide. Control of 2
      alkenylfuran (E/Z)-configuration.
AB  - [reaction: see text] The convergent synthesis of the fully functionalized C(1)
      C(18) segment 24 of the furanocembranes lophotoxin and pukalide was accomplished
      in 11 steps and 10% overall yield. The key step was a stereoselective conversion
      of alkynoate 21 to trimethylsilyl 2-alkenylfuran 22.

PMID- 12000300
TI  - Cucurbit[7]uril: a very effective host for viologens and their cation radicals.
AB  - [reaction: see text] The host cucurbit[7]uril (CB7) forms very stable inclusion
      complexes with simple 4,4'-bipyridinium (viologen) dication guests in aqueous
      solution. The binding constants were measured by electronic absorption
      spectroscopy and found to be as high as 1 x 10(5) L/mol. One-electron reduction
      of the viologen guest results in a modest 2-fold decrease of the binding
      constant. The rate of the heterogeneous electron-transfer reaction between the
      complexed viologen dication and cation radical remained fast in the voltammetric
      time scale.

PMID- 12000301
TI  - Catalyst-controlled diastereoselective hetero-Diels-Alder reactions.
AB  - [reaction: see text] The diastereoselective hetero-Diels-Alder reaction between
      Danishefsky's diene and chiral aldehydes is catalyzed by chiral chromium-Schiff
      base complexes. High levels of catalyst control are obtained in several cases,
      allowing access to all four stereoisomeric products through appropriate choice of
      aldehyde and catalyst enantiomers.

PMID- 12000302
TI  - Synthesis of dinucleoside (N3'-->MeP5') methanephosphonamidates.
AB  - [structure: see text] Three different approaches were used for the synthesis of
      dinucleoside methanephosphonamidates [3'-NH-P(O)(CH3)O-5'], starting from
      dichloromethylphosphine or dichloromethanephosphonate as the phosphorus
      containing moiety. 5'-DMT-3'-amino-3'-deoxythymidine and N(4)-benzoyl-5'-DMT-3'
      amino-2',3'-dideoxycytidine were used as the aminonucleoside precursors and the
      respective 3'-protected nucleosides (thymidine or N(4)-benzoyl-2'-deoxycytidine)
      as the 5'-hydroxyl reagents.

PMID- 12000303
TI  - Conversion of carbamates to amidosulfones and amides. Synthesis of the [14C]
      labeled antiobesity agent Ro23-7637.
AB  - [reaction: see text] Carbamates of primary and secondary amines react with the
      dianion of methyl phenyl sulfone to yield amidosulfones. Alylation of the
      amidosulfone followed by reductive removal of the sulfonyl residue gives an
      amide.

PMID- 12000304
TI  - Synthesis and cholera toxin binding properties of a lactose-2-aminothiazoline
      conjugate.
AB  - [structure: see text] During the search for improved monovalent ligands for
      cholera toxin (CT), a new lactose-2-aminothiazoline conjugate was discovered. In
      a fluorescence binding assay the compound was found to be one of the strongest
      relatively simple CT ligands to date with a K(d) of 23 microM.

PMID- 12000305
TI  - Concise, stereoselective syntheses of cis-nemorensic acid and 4-hydroxy-cis
      nemorensic acid via tandem carbonyl ylide formation-cycloaddition.
AB  - [reaction: see text] 1,3-Dipolar cycloaddition of propargyl bromide with the
      carbonyl ylide derived from 6-diazoheptane-2,5-dione is the key step in concise
      syntheses of cis-nemorensic acid and 4-hydroxy-cis-nemorensic acid.

PMID- 12000306
TI  - Synthesis of cryptophycin 52 using the Shi epoxidation.
AB  - [reaction: see text] A synthesis of cryptophycin 52 is reported using a Shi
      epoxidation strategy to install the epoxide moiety in a diastereoselective
      fashion. Several epoxidation results for cryptophycin substrates are disclosed
      followed by a discussion of the details relating to the preparation of
      cryptophycin 52 in two synthetic steps from one of the intermediate epoxides.

PMID- 12000309
TI  - Foxa3 (HNF-3gamma) binds to and activates the rat proglucagon gene promoter but
      is not essential for proglucagon gene expression.
AB  - Members of the Forkhead box a (Foxa) transcription factor family are expressed in
      the liver, pancreatic islets and intestine and both Foxa1 and Foxa2 regulate
      proglucagon gene transcription. As Foxa proteins exhibit overlapping DNA-binding
      specificities, we examined the role of Foxa3 [hepatocyte nuclear factor (HNF)
      3gamma] in control of proglucagon gene expression. Foxa3 was detected by reverse
      transcriptase PCR in glucagon-producing cell lines and binds to the rat
      proglucagon gene G2 promoter element in GLUTag enteroendocrine cells. Although
      Foxa3 increased rat proglucagon promoter activity in BHK fibroblasts,
      augmentation of Foxa3 expression did not increase proglucagon promoter activity
      in GLUTag cells. Furthermore, adenoviral Foxa3 expression did not affect
      endogenous proglucagon gene expression in islet or intestinal endocrine cell
      lines. Although Foxa3(-/-) mice exhibit mild hypoglycaemia during a prolonged
      fast, the levels of proglucagon-derived peptides and proglucagon mRNA transcripts
      were comparable in tissues from wild-type and Foxa3(-/-) mice. These findings
      identify Foxa3 as a member of the proglucagon gene G2 element binding-protein
      family that, unlike Foxa1, is not essential for control of islet or intestinal
      proglucagon gene expression in vivo.

PMID- 12000310
TI  - Interaction of heparin with internally quenched fluorogenic peptides derived from
      heparin-binding consensus sequences, kallistatin and anti-thrombin III.
AB  - Internally quenched fluorogenic (IQF) peptides bearing the fluorescence
      donor/acceptor pair o-aminobenzoic acid (Abz)/N-(2,4
      dinitrophenyl)ethylenediamine (EDDnp) at N- and C-terminal ends were synthesized
      containing heparin-binding sites from the human serpins kallistatin and
      antithrombin, as well as consensus heparin-binding sequences (Cardin clusters).
      The dissociation constant (K(d)), as well as the stoichiometry for the heparin
      peptide complexes, was determined directly by measuring the decrease in
      fluorescence of the peptide solution. Experimental procedures were as sensitive
      as those used to follow the fluorescence change of tryptophan in heparin-binding
      proteins. The conformation of the peptides and the heparin-peptide complexes were
      obtained from measurements of time-resolved fluorescence decay and CD spectra.
      Kallistatin (Arg(300)-Pro(319))-derived peptide (HC2) and one derived from
      antithrombin III helix D [(AT3D), corresponding to Ser(112)-Lys(139)], which are
      the heparin-binding sites in these serpins, showed significant affinity for 4500
      Da heparin, for which K(d) values were 17 nM and 100 nM respectively. The CD
      spectra of the heparin-HC2 peptide complex did not show any significant alpha
      helix content, different from the situation with peptide AT3D, for which complex
      formation with heparin resulted in 24% alpha-helix content. The end-to-end
      distance distribution and the time-resolved fluorescence-decay measurements agree
      with the CD spectra and K(d) values. The synthetic alpha-methyl glycoside
      pentasaccharide AGA*IA(M) (where A represents N,6-O-sulphated alpha-d
      glucosamine; G, beta-d-glucuronic acid; A*, N,3,6-O-sulphated alpha-d
      glucosamine; I, 2-O-sulphated alpha-l-iduronic acid; and A(M), alpha-methyl
      glycoside of A) also binds to AT3D and other consensus heparin-binding sequences,
      although with lower affinity. The interaction of IQF peptides with 4500 Da
      heparin was displaced by protamine. In conclusion, IQF peptides containing
      Abz/EDDnp as the donor/acceptor fluorescence pair are very promising tools for
      structure-activity relationship studies on heparin-peptide complexes, as well as
      for the development of new peptides as heparin reversal-effect compounds.

PMID- 12000312
TI  - Symposium: Helicobacter pylori and clinical risks--focus on gastro-oesophageal
      reflux disease.
AB  - Helicobacter pylori is a gastric pathogen that is a major cause of peptic ulcer
      disease, has a role in mucosa-associated lymphoid tissue (MALT) lymphoma and is
      associated with gastric cancer. Yet, in a large proportion of the human
      population, H. pylori infection has no apparent adverse clinical consequences.
      Furthermore, recent research suggests that H. pylori may even confer protection
      against gastroesophageal reflux disease. The conflicting evidence surrounding H.
      pylori infection was discussed at a sponsored symposium in Helsinki, introduced
      by Professor P. Malfertheiner, with papers presented by Dr H. J. O'Connor,
      Professor R. M. Genta, Dr P. Unge and Professor A. T. R. Axon. Emerging
      epidemiological and retrospective evidence suggests that the presence of H.
      pylori infection may provide some protection against gastroesophageal reflux
      disease, but there is other evidence that shows no benefit of H. pylori for the
      protection of the oesophagus. It was felt that prospective, multicentre studies
      are needed to explore the H. pylori-gastroesophageal disease relationship
      further, to avoid confusing potential benefits with known risks. Following the
      symposium, a discussion on the relative risks and benefits for H. pylori
      eradication was provided by Professor Axon and Professor Blaser. Eradication of
      H. pylori has been recommended in a series of management guidelines issued by
      consensus groups. However, accurate estimates of the relative risks and benefits
      of H. pylori infection in the general population, as well as in specific patient
      groups, is essential in order to develop a management strategy.

PMID- 12000311
TI  - Fibroblast growth factor-2 binds to small heparin-derived oligosaccharides and
      stimulates a sustained phosphorylation of p42/44 mitogen-activated protein kinase
      and proliferation of rat mammary fibroblasts.
AB  - We examine the relationship between the chain length of heparin-derived
      oligosaccharides, fibroblast growth factor (FGF)-2 binding kinetics and the
      ability of the oligosaccharides to allow FGF-2-induced proliferation of chlorate
      treated rat mammary fibroblasts. First, using an optical biosensor, we show that
      FGF-2 did not bind disaccharides, but definitively bound to tetrasaccharides. As
      the chain length increased from tetrasaccharide to octasaccharide, there was a
      substantial increase in k(ass) (564000 M(-1) x s(-1) to 2000000 M(-1) x s(-1),
      respectively) and affinity (K(d) 77 nM to 11 nM, respectively) for FGF-2. From
      decasaccharides and longer, the k(ass) and affinity for FGF-2 was reduced
      substantially (tetradecasaccharide k(ass) 470000 M(-1) x s(-1), K(d) 30 nM). In
      chlorate-treated, and hence sulphated, glycosaminoglycan-deficient cells, FGF-2
      alone or in the presence of disaccharides did not stimulate DNA synthesis and it
      only elicited an early transient dual phosphorylation of p42/44 mitogen-activated
      protein kinase (MAPK). In the same cells FGF-2 in the presence of
      tetrasaccharides and longer oligosaccharides was able to restore DNA synthesis
      and enable the sustained dual phosphorylation of p42/44(MAPK). However, the
      oligosaccharides from tetrasaccharides to octasaccharides were less potent in
      proliferation assays than deca- and longer oligosaccharides. Therefore, there was
      no correlation between the binding parameters and the potency of the
      oligosaccharides in DNA synthesis assays. These results demonstrate that
      tetrasaccharides are able to bind FGF-2 and enable FGF-2 to stimulate cell
      proliferation, which sets important boundary conditions for models of the FGF-2
      heparan sulphate-FGF receptor complex.

PMID- 12000313
TI  - Metabolic modelling of microbes: the flux-balance approach.

PMID- 12000314
TI  - Predominant growth of Alcanivorax strains in oil-contaminated and nutrient
      supplemented sea water.
AB  - We found that bacteria closely related to Alcanivorax became a dominant bacterial
      population in petroleum-contaminated sea water when nitrogen and phosphorus
      nutrients were supplied in adequate quantity. The predominance of Alcanivorax
      bacteria was demonstrated under three experimental conditions: (i) in batch
      cultures of sea water containing heavy oil; (ii) in columns packed with oil
      coated gravel undergoing a continuous sea water flow; and (iii) in a large-scale
      tidal flux reactor that mimics a beach undergoing tidal cycles with fresh sea
      water. These results suggest that bacteria related to Alcanivorax are major
      players in the bioremediation of oil-contaminated marine environments.

PMID- 12000315
TI  - Population dynamics of type I and II methanotrophic bacteria in rice soils.
AB  - Methane-oxidizing bacteria (methanotrophs) consume a significant but variable
      fraction of greenhouse-active methane gas produced in wetlands and rice paddies
      before it can be emitted to the atmosphere. Temporal and spatial dynamics of
      methanotroph populations in California rice paddies were quantified using
      phospholipid biomarker analyses in order to evaluate the relative importance of
      type I and type II methanotrophs with depth and in relation to rice roots.
      Methanotroph population fluctuations occurred primarily within the top 0-2 cm of
      soil, where methanotroph cells increased by a factor of 3-5 over the flooded rice
      growing season. The results indicate that rice roots and rhizospheres were less
      important than the soil-water interface in supporting methanotroph growth. Both
      type I and type II methanotrophs were abundant throughout the year. However, only
      type II populations were strongly correlated with soil porewater methane
      concentrations and rice growth.

PMID- 12000316
TI  - Occurrence and activity of Archaea in aerated activated sludge wastewater
      treatment plants.
AB  - The occurrence, distribution and activity of archaeal populations within two
      aerated, activated sludge wastewater treatment systems, one treating domestic
      waste and the second treating mixed domestic and industrial wastewater, were
      investigated by denaturing gradient gel electrophoresis (DGGE) analysis of
      polymerase chain reaction (PCR)-amplified ribosomal RNA gene fragments and
      process measurements. In the plant receiving mixed industrial and domestic waste
      the archaeal populations found in the mixed liquor were very similar to those in
      the influent sewage, though a small number of DGGE bands specific to the mixed
      liquor were identified. In contrast, the activated sludge treating principally
      domestic waste harboured distinct archaeal populations associated with the mixed
      liquor that were not prevalent in the influent sewage. We deduce that the Archaea
      in the plant treating mixed wastewater were derived principally from the
      influent, whereas those in the plant treating solely domestic waste were actively
      growing in the treatment plant. Archaeal 16S rRNA gene sequences related to the
      Methanosarcinales, Methanomicrobiales and the Methanobacteriales were detected.
      Methanogenesis was measured in activated sludge samples incubated under oxic and
      anoxic conditions, demonstrating that the methanogens present in both activated
      sludge plants were active only in anoxic incubations. The relatively low rates of
      methanogenesis measured indicated that, although active, the methanogens play a
      minor role in carbon turnover in activated sludge.

PMID- 12000317
TI  - Enrichment versus biofilm culture: a functional and phylogenetic comparison of
      polycyclic aromatic hydrocarbon-degrading microbial communities.
AB  - The effect that culture methods have on the diversity of degradative microbial
      communities is not well understood. We compared conventional batch enrichment
      with a biofilm culture method for the isolation of polycyclic aromatic
      hydrocarbon (PAH)-degrading microbial communities from a PAH-contaminated soil.
      The two methods were assessed by comparing: (i) the diversity of culturable
      bacteria; (ii) the diversity of PAH-catabolic genes in isolated bacteria; (iii)
      the inter- and intraspecific diversity of active PAH-catabolic gene classes; (iv)
      the diversity of bacteria present in 16S rRNA gene libraries generated from RNA
      extracted from the two communities and soil; and (v) the estimated diversity of
      active bacteria in the soil and culture systems. Single-strand conformation
      polymorphism analysis showed that the biofilm culture yielded 36 bacterial and
      two fungal species compared with 12 bacterial species from the enrichment
      culture. Application of accumulation and non-parametric estimators to clone
      libraries generated from 16S rRNA confirmed that the biofilm community contained
      greater diversity. Sequencing of clones showed that only species from the
      Proteobacteria were active in the enrichment culture, and that these species were
      expressing an identical nahAc-like naphthalene dioxygenase. 16S rRNA clones
      generated from the biofilm community indicated that species from the
      Cytophaga/Flavobacterium, high G+C bacteria and Proteobacteria were active at the
      time of sampling, expressing cndA-, nahAc- and phnAc-like naphthalene
      dioxygenases. The diversity of active species in the biofilm culture system
      closely matched that in the PAH-contaminated source soil. The results of this
      study showed that biofilm culture methods are more appropriate for the study of
      community-level interactions in PAH-degrading microbial communities. The study
      also indicated that cultivation of microbial communities on solid media might be
      the primary source of bias in the recovery of diverse species.

PMID- 12000318
TI  - Substrate-regulated cyanide hydratase (chy) gene expression in Fusarium solani:
      the potential of a transcription-based assay for monitoring the biotransformation
      of cyanide complexes.
AB  - The fungus Fusarium solani detoxifies cyanide through induction of the cyanide
      hydratase gene activity (chy) in the presence of either KCN or the metal
      complexed cyanides, K2Ni(CN)4 or K4Fe(CN)6, at pH 7.0 and 4.0 respectively.
      Sequence analysis of the chy gene identified primers for reverse transcriptase
      polymerase chain reaction (RT-PCR)-directed analysis of mRNA transcripts, which
      demonstrated that activity correlated to the substrate-specific induction of gene
      expression. chy transcription was initiated 30-60 min after exposure of F. solani
      cultures to cyanide complexes. Maximum expression was detected within 4.5 h,
      after which chy mRNA synthesis declined below the limits of detection within 26
      h. A lag period of approximately 2 h, following initial transcription, was
      recorded before cyanide complexes were converted to formamide. mRNA transcripts
      of chy were not detected in the absence of cyanide or cyanide complexes. The
      presence of introns within the gene resulted in a difference in size of 100 bp
      for DNA compared with mRNA of the corresponding 5' region. This size difference
      facilitated PCR detection of gene and transcript respectively. Comparisons of the
      predicted amino acid sequence of the F. solani chy gene and those of
      Gloeocerospora sorghi, Fusarium lateritium and Leptosphaeria maculans demonstrate
      that cyanide hydratase genes are highly conserved and of a similar evolutionary
      origin. These data predict that the functional assay described here to monitor
      the induction of chy gene expression and, potentially, cyanide degradation would
      be applicable to a variety of polluted environments.

PMID- 12000320
TI  - Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion
      imaging. A report from the Standardization Group of the European Society of
      Contact Dermatitis based upon the HIRELADO European community project.
AB  - This report reviews how to set up a laser Doppler perfusion imaging system
      intended for visualization of skin blood perfusion, capture images and evaluate
      the results obtained. A brief summary of related papers published in the
      literature within the areas of skin irritant and allergy patch testing,
      microdialysis and skin tumour circulation is presented, as well as early
      applications within other fields such as diabetology, wound healing and
      microvascular research.

PMID- 12000321
TI  - Fragrance contact dermatitis - a worldwide multicenter investigation (Part III).
AB  - The purpose of this study was to determine the frequency of responses to selected
      fragrance materials in patients who were fragrance sensitive. 218 fragrance
      sensitive subjects were evaluated in eight centres worldwide with a fragrance
      mixture (FM) and 17 less well-studied fragrance materials. Reaction to the
      fragrance mixture (FM) occurred in 76% of the subjects. The (FM) detected all
      reactions to nerol and hydroxycitronellol and 93% of the reactions to clove bud
      oil. Ten fragrance materials were not detected by the FM and deserve further
      study: benzenepropanol, beta, beta, 3-trimethyl, hexyl-salicylate, dl
      citronellol, synthetic ylang ylang oil, benzyl mixture, cyclohexyl-acetate,
      eugenyl methyl ether, isoeugenyl methyl ether, 3-phenyl-1-propanol, and 3, 7
      dimethyl-7-methoxyoctan-2-ol.

PMID- 12000322
TI  - Contact allergens in shoe leather among patients with foot eczema.
AB  - Some patients with relapsing foot eczema and a shoe leather allergy, who fail to
      show positive results with standard series and shoe wear screening tray patch
      testing, do not respond to the use of hypoallergenic shoe leather. We assume that
      relevant allergens are present in hypoallergenic shoe leather. We described an
      experiment to demonstrate the presence of these allergens. Alcoholic extracts
      were made of green, black and undyed hypoallergenic shoe leather, and the
      extracts were fractioned by paper chromatography. The resulting chromatograms
      were cut into 16 equal paper disks and patch tests were performed with extracts
      and the paper chromatography fractions. Positive reactions were seen to all
      extracts and to fractions of all types of leather. From analysis of the pattern
      of positive patch tests we concluded that leather-related allergens (e.g. tanning
      agent) and dyes were present in hypoallergenic shoe leather. In these cases,
      alternatives to shoe leather should be sought, for instance wooden or plastic
      shoes.

PMID- 12000323
TI  - Allergic contact dermatitis from shellac in mascara.
AB  - We report 6 cases of allergic contact dermatitis of the eyelids due to mascara.
      Allergy occurred in women aged 17-34 years, between September 1999 and June 2001.
      The main ingredient responsible for allergy was shellac, which gave positive
      patch test reactions in 5/5 patients. This resinous substance is mainly used in
      cosmetics, food and industry. The exact nature of the hapten remains unknown, and
      its presence and level in shellac can vary with the source and the treatments
      applied to it. One patient was also sensitized to quaternium-22, a quaternary
      ammonium compound in the cosmetic. These reports underline the role of networks,
      such as REVIDAL-GERDA, in monitoring the emergence of contact allergens and
      disseminating such information among the medical community.

PMID- 12000324
TI  - The preservative iodopropynyl butylcarbamate: frequency of allergic reactions and
      diagnostic considerations.
AB  - The preservative iodopropynyl butylcarbamate (IPBC) (0.1% in petrolatum) was
      tested in 4883 consecutive patients for 18 months between January 1998 and June
      1999. With regard to the MOAHLFA-Index, the study population comprised 37% males;
      17% with occupational and 19% with atopic dermatitis; 31% with hand, 10% with leg
      and 17% with face dermatitis; 61% were age 40 and above. According to readings at
      D3, 0.3% were allergic to IPBC, with 14 + and 2 + + reactions. Doubtful or
      irritant reactions occurred twice as frequently. Patients exposed for 24 h (n =
      1814) reacted less frequently (0.1%) than the remaining patients exposed for 48 h
      (0.5%). Considering the possibility that a certain proportion of + reactions
      could be false positive, the reaction pattern was evaluated. More than 80% of the
      positive reactions displayed a crescendo or plateau time pattern. Furthermore, 18
      of 43 doubtful reactions (?) appeared as late as D3 (thus, these could be false
      negative), whereas the majority of doubtful reactions occurred earlier and
      displayed a decrescendo pattern (corresponding to a typical irritant pattern). In
      conclusion, the large proportion of '?' reactions may be due not only to the
      irritant potential of the substance, but also to test concentrations not being
      high enough to elicit an allergic reaction. We propose that higher concentrations
      of IPBC (0.3%) should be evaluated in a study also addressing suitable validation
      tests like ROAT or PUT.

PMID- 12000325
TI  - Oak moss extracts in the diagnosis of fragrance contact allergy.
AB  - Oak moss absolute is one of the eight ingredients of the fragrance mix (FM) used
      for diagnosing perfume allergy. Oak moss absolute is an extract prepared from the
      lichen Evernia prunastri growing on oak trees. It has been shown that the oak
      moss patch test material from one producer contained resin acids which are
      ingredients of another lichen, tree moss. Resin acids, e.g. abietic acid and
      dehydroabietic acid, are also the main allergens in colophonium. The aim of the
      study was to assess whether the contamination of oak moss absolute and thus the
      FM with resin acids had affected their diagnostic value so that they, instead of
      indicating fragrance allergy, had become indicators of allergy to resin acids and
      thus colophonium. Two studies were undertaken. First the relationship between
      patch test reactions to FM, oak moss absolute, both with contents of resin acids,
      and colophonium were assessed in 885 consecutive patients. A significant
      relationship between reactions to colophonium and FM was seen (p < 0.001) as well
      as a significant relationship between oak moss absolute and colophonium (p <
      0.001). The relationship between colophonium and FM was still significant when
      all reactions to oak moss absolute were disregarded (p < 0.001), showing a
      relationship also between colophonium and fragrance ingredients other than oak
      moss absolute. Second, 119 consecutive patients were tested with an old and a new
      version of oak moss absolute containing resin acid (0.05%) and no measurable
      resin acid, respectively, and with the corresponding FM. No overall difference in
      reactivity to the old and new version of oak moss absolute/FM was seen. It is
      concluded the diagnostic value of oak moss absolute as indicator fragrance
      contact allergy has been and is unaffected by the resin acid contamination.

PMID- 12000326
TI  - Ethnic variations in self-perceived sensitive skin: epidemiological survey.
AB  - To examine possible ethnic variations in perception of sensitive skin, an
      epidemiological survey was performed in the San Francisco area. Approximately 800
      telephone interviews were conducted with women from four different ethnic groups
      (Afro-Americans, Asians, Euro-Americans, Hispanics; approximately 200 women per
      group). In addition to sensitive facial skin assessments, age and other general
      skin condition data were collected. 52% of the subjects identified themselves as
      having sensitive facial skin. There was no statistical difference between the
      ethnic groups in terms of sensitive skin prevalence. Nevertheless, some
      differences were noted between ethnic subgroups of sensitive skin. Euro-Americans
      were characterized by a higher skin reactivity to wind and tended to be less
      reactive to cosmetics. Afro-Americans presented diminished skin reactivity to
      most environmental factors and a lower frequency of recurring facial redness.
      Asians appeared to have greater skin reactivity to spicy food, to sudden changes
      in temperature and to wind, and tended to suffer from itching more frequently.
      Hispanics presented a lower incidence of skin reactivity to alcohol. The
      differences in skin sensitivity between ethnic groups concerned mostly factors of
      skin reactivity and, to a lesser extent, its symptomatology. But, taken together,
      we note the similarities in comparing how women of varying ethnic backgrounds
      perceive the sensitive skin condition.

PMID- 12000327
TI  - Identification of sensitizing diethyleneglycol maleate in a two-component
      polyester cement.
AB  - Unsaturated polyester (UP) cement caused allergic contact dermatitis in car
      repair work. The resin was a condensate of polyols and maleic anhydride with
      reactive solvent, auxiliary substances, and inorganic reinforcement substances.
      To identify the causative chemicals, the cement was tested on a sensitized
      patient. For analysis, samples of the resin were eluted with acetone and eluted
      with hexane to precipitate inorganic material and large polyester molecules. The
      eluate was evaporated. The remainder, dissolved in acetone, was separated into
      fractions on silica plates by thin layer chromatography (TLC). On the developed
      (hexane/chloroform, 15/85) plates, 20 bands were obtained under UV-light at 254
      nm. Samples of the bands were scraped and used for patch testing. The scraping at
      a retention factor (Rf) of 0.24 caused a skin reaction. The bands at this
      retention were removed from six plates, combined, eluted with acetone and
      purified again by TLC. The purified fraction mixed in petrolatum in the dilution
      series was used for conclusive patch testing on the patient. An allergic reaction
      was induced at down to 0.003% wt/wt. According to MS and IR analyses, the
      isolated compound was diethyleneglycol maleate (DEGM, MW204). In addition to the
      resin part, the sanding dust also contained this monomer.

PMID- 12000328
TI  - Fixed drug eruption from piroxicam with positive lesional patch test.

PMID- 12000329
TI  - Erythema multiforme associated with blister beetle dermatitis.

PMID- 12000330
TI  - Cocospropylenediamine-guanidinium diacetate: synonyms and cross-reactants.

PMID- 12000331
TI  - Contact dermatitis from benzoyl peroxide in dental prostheses.

PMID- 12000332
TI  - Irritant contact dermatitis from the jellyfish Rhizostoma pulmo.

PMID- 12000333
TI  - Occupational protein contact dermatitis from shrimps. A new presentation of the
      crustacean-mite syndrome.

PMID- 12000334
TI  - Staphylinid blister beetle dermatitis.

PMID- 12000335
TI  - Airborne allergic contact dermatitis from olaquindox in a rabbit breeder.

PMID- 12000336
TI  - Erythema multiforme from sulfaguanidine.

PMID- 12000337
TI  - Allergic contact dermatitis from black cumin (Nigella sativa) oil-containing
      ointment.

PMID- 12000338
TI  - Effect of contact media on the diagnostic quality of electrical resistance
      measurements for occlusal caries.
AB  - BACKGROUND: Electrical resistance measurements have been used for the diagnosis
      of occlusal caries. Both site and surface-specific techniques have been
      described, the latter more suited to clinical trials or epidemiological surveys.
      For surface-specific measurements the tooth is dried and a contact medium drawn
      along the fissure pattern to provide an electrical contact between a probe tip
      and the tooth surface. OBJECTIVES: Different contact media have been used and it
      was the aim of this study to investigate whether different contact media could
      influence the diagnostic accuracy and repeatability of surface-specific
      electrical resistance measurements. METHODS: Electrical resistance readings were
      taken on 99 molar teeth using saline, KY jelly, toothpaste or dental prophylaxis
      paste. Readings were repeated on 44 randomly selected teeth. The teeth were
      serially sectioned and visually examined to establish the deepest lesion if
      present. RESULTS: The Student t-test showed that there were statistically
      significant differences between readings taken with different contact media, with
      the exception of toothpaste and prophylaxis paste, where no difference was found.
      The strongest relationship between histology and resistance reading was achieved
      with KY jelly (r = 0.559). The optimum sensitivity and specificity achieved was
      0.59 and 0.86, respectively (resistance cut-off 0.1 M(Omega)). ROC analysis
      showed that the diagnostic performance of saline was significantly inferior to
      the other contact media (P < 0.05). Limits of agreement were used to assess
      repeatability which were acceptable for all media except toothpaste. CONCLUSIONS:
      Differences were found between electronic resistance readings taken with
      different contact media. KY jelly was found to produce the best overall
      diagnostic performance and should be the standard material used for surface
      specific measurements.

PMID- 12000339
TI  - The Dental Neglect and Dental Indifference scales compared.
AB  - OBJECTIVES: The objective was to determine whether the Dental Neglect and Dental
      Indifference scales measure similar constructs and have similar associations in
      the same population sample. METHODS: A random sample of 600 residents in the
      Dunedin South Electorate were sent a self-report questionnaire containing the
      Dental Neglect scale and the Dental Indifference scale. Socio-demographic and
      dental service-use data were also collected. RESULTS: In all, 478 people (78.2%)
      returned the questionnaire. The mean Dental Neglect score was 12.4 (SD 4.4). The
      mean Dental Indifference scale score was 3.1 (SD 1.9). The association between
      the scales' scores was moderate (r = 0.58; P < 0.01), and there was only a
      moderate degree of concordance between the two. The two scales had largely
      similar associations with socio-demographic, oral care and self-care, and oral
      health impact characteristics, although slightly more associations were found
      with the Dental Indifference scale. The Dental Neglect scale was found to be
      easier to use than the Dental Indifference scale because it did not require a
      complex algorithm to compute scale scores. CONCLUSIONS: The degree of concordance
      between the Dental Neglect and Dental Indifference scales was not as high as
      expected, which suggests that the scales may measure different constructs.
      However, the largely similar associations with important oral health and socio
      demographic variables of the scales suggest the opposite. Although the Dental
      Indifference scale was slightly more discriminative, the Dental Neglect scale was
      easier to use in practice.

PMID- 12000340
TI  - Maternal risk indicators for childhood caries in an inner city population.
AB  - OBJECTIVES: This study evaluated whether characteristics of mothers, such as high
      mutans streptococci (MS) level, caries experience, reported sugar consumption and
      demographic variables, could be important risk indicators of caries for their
      children. METHODS: Mothers selected on the basis of the caries status of their 3
      5-year-old-children were tested for MS, caries, reported sugar consumption and
      demographic variables. RESULTS: We found strong associations between children's
      caries and their mothers' MS levels (high/low adj. OR = 11.3), maternal active
      caries (yes/no adj. OR = 4.0) and maternal sugar consumption (high/low adj. OR =
      4.2). In this small study, mothers' demographic variables were not associated
      with the status of caries in their children. CONCLUSIONS: Our findings suggest
      that maternal high MS levels, maternal active decay and maternal sugar
      consumption are strong risk indicators for children's caries. Although further
      study is needed, these three maternal risk indicators, taken together, may prove
      useful in predicting children's caries risk.

PMID- 12000341
TI  - Glycemic control of type 2 diabetes and severe periodontal disease in the US
      adult population.
AB  - OBJECTIVE: We investigated the association between glycemic control of type 2
      diabetes mellitus (type 2 DM) and severe periodontal disease in the US adult
      population ages 45 years and older. METHODS: Data on 4343 persons ages 45-90
      years from the National Health and Nutrition Examination Study III were analyzed
      using weighted multivariable logistic regression. Severe periodontal disease was
      defined as 2 + sites with 6 + mm loss of attachment and at least one site with
      probing pocket depth of 5 + mm. Individuals with fasting plasma glucose > 126
      mg/dL were classified as having diabetes; those with poorly controlled diabetes
      (PCDM) had glycosylated hemoglobin > 9% and those with better-controlled diabetes
      (BCDM) had glycosylated hemoglobin <or= 9%. Additional variables evaluated in
      multivariable modeling included age, ethnicity, education, gender, smoking
      status, and other factors derived from the interview, medical and dental
      examination, and laboratory assays. RESULTS: Individuals with PCDM had a
      significantly higher prevalence of severe periodontitis than those without
      diabetes (odds ratio = 2.90; 95% CI: 1.40, 6.03), after controlling for age,
      education, smoking status, and calculus. For the BCDM subjects, there was a
      tendency for a higher prevalence of severe periodontitis (odds ratio = 1.56; 95%
      CI: 0.90, 2.68). CONCLUSION: These results provide population-based evidence to
      support an association between poorly controlled type 2 diabetes mellitus and
      severe periodontitis.

PMID- 12000342
TI  - Impact of traumatic injuries to the permanent teeth on the oral health-related
      quality of life in 12-14-year-old children.
AB  - BACKGROUND/AIM: There are no data on the impacts on daily living of traumatic
      injuries to the permanent teeth. The aim of the present study was to assess the
      socio-dental impacts of untreated fractured anterior teeth in Brazilian
      schoolchildren. METHODS: A population-based matched case-control study was used
      and a 2 : 1 control-to-case ratio was adopted. The cases were 68 children 12-14
      years old, having non-restored teeth, with fracture involving dentine. The
      controls were 136 children without any traumatic dental injury. They were matched
      by age, sex and socio-economic status. The Oral Impact on Daily Performances
      (OIDP) index was used to measure the impacts. RESULTS: The response rate was
      100%. Results of conditional logistic regression showed that children with
      fractured teeth were 20 times (95% CI = 2.2-45.6) more likely to report any
      impact on their daily living than children with no traumatic dental injury. These
      results remained statistically significant for the items of the OIDP separately,
      'smiling' (P < 0.001), 'maintaining emotional state' (P < 0.001), 'eating' (P <
      0.01), 'enjoying contact with people' (P < 0.01) and the overall OIDP (P <
      0.001), after adjusting for confounding variables such as the Aesthetic Component
      of the Index of Orthodontic Treatment Need and DMFT index in a multiple
      conditional logistic regression. CONCLUSIONS: Children with untreated dental
      fracture of permanent teeth had more impacts on their daily living than children
      without any traumatic injury.

PMID- 12000343
TI  - Esthetically objectionable fluorosis attributable to water fluoridation.
AB  - OBJECTIVE: We compared estimates of fluorosis prevalence and risk attributable to
      fluoridation using an index applied to the entire dentition and to the maxillary
      anterior teeth. We also estimated the prevalence of perceived esthetic problems
      attributable to current fluoridation policy (Attributable Burden). METHODS:
      Fluorosis prevalence estimates were obtained from the National Survey of Oral
      Health in US School Children (1986-87) for the 1839 survey children aged 12 -14
      years who were scored for fluorosis, had never received fluoride drops or
      tablets, and had lived in only one home. For each child we calculated Dean's
      fluorosis index, and an anterior fluorosis index (value of the highest scored
      maxillary anterior tooth). We used each index to calculate risk of fluorosis
      attributable to fluoridation by subtracting at each level of severity the
      prevalence of fluorosis among those living in low fluoride areas (F <or= 0.3 ppm)
      from the prevalence among those living in optimally fluoridated areas (0.7 ppm F
      <or=1.2 ppm). Findings from five published studies were used to calculate risk of
      perceived esthetic problem attributable to fluorosis, by severity, i.e. the
      difference in the mean percentage of respondents who were satisfied with the
      appearance of their teeth with and without fluorosis. Finally, Attributable
      Burden was estimated by summing the products of risk of perceived esthetic
      problems attributable to fluorosis and risk of fluorosis attributable to
      fluoridation for each level of fluorosis severity. RESULTS: Prevalence of
      fluorosis, very mild or greater, was 26% with Dean's Index, which was
      significantly higher than the 18% figure calculated with the anterior index.
      Using the anterior index, fluoridation was a risk factor for very mild
      (attributable risk = 15%) and mild fluorosis (attributable risk = 3%). Risk of
      fluorosis (very mild or greater) attributable to fluoridation was significantly
      higher when calculated from prevalence estimates using Dean's Index than
      estimates calculated with the anterior index (24% versus 18%). The mean values of
      risk of perceived esthetic problems attributable to very mild and mild fluorosis
      were 9% and 33%, respectively. CONCLUSION: We found that approximately 2% of US
      schoolchildren may experience perceived esthetic problems which could be
      attributed to the currently recommended levels of fluoride in drinking water. The
      findings further suggest that both estimates of fluorosis prevalence and risk of
      fluorosis attributable to fluoridation will be higher when calculated with an
      index applied to the entire dentition. Data were unavailable for fluoridated
      toothpaste and diluted formula consumption, thus the risk of fluorosis
      attributable to fluoridation may be overestimated if consumption was higher in
      fluoridated areas. The risk of perceived esthetic problems attributable to
      fluoridation must be weighed against its lifetime benefits and the associated
      costs of alternative solutions such as educating parents about appropriate
      toothpaste use and lowering the fluoride content of children's toothpaste.

PMID- 12000344
TI  - Targeting dental sealants in school-based programs: evaluation of an approach.
AB  - Several guidelines have been published in the United States to promote the
      appropriate use of sealants in both individual care and public health programs.
      Targeting sealants to children and teeth at high risk for dental caries has been
      accepted as a desirable strategy in school-based programs. However, there is
      little evidence to show that programs are complying with these guidelines. This
      report examined the extent to which sealants were targeted to high-risk children
      at 11 different school-based programs in New York State. Data on 3357 children
      ages seven to nine were analyzed. The percent of children receiving sealants
      ranged from 41% to 88%. While in two sites (St. Lawrence & Onondaga) fewer than
      52% of the children received sealants; more than 73% received sealants in the
      remaining nine sites (P < 0.05). The results suggest that there was a wide
      variation in the implementation of the guidelines for sealant use. Some reasons
      for not adhering to the guidelines were: difficulty in assuring parents and local
      dentists that some children were not at risk for caries; lack of confidence in
      the risk-assessment method; uncertainty regarding what constitutes deep pits and
      fissures; fear of misclassifying children and requests by school administrators,
      parents and local dentists that all children should benefit from preventive
      measures.

PMID- 12000345
TI  - Oral self-care among adults with diabetes in Finland.
AB  - OBJECTIVES: The importance of maintenance and promotion of periodontal health is
      emphasized among people with diabetes because of their high risk for periodontal
      diseases. Our aim was to evaluate oral health behavior and its determinants among
      adults with diabetes in Finland. METHODS: The population of the questionnaire
      study consisted of 420 systematically selected adults with diabetes, who were
      members of a national diabetes register. The response rate was 80%. Questions
      focused on self-treatment, -prevention, and -diagnosis of oral diseases,
      utilization of dental services, and knowledge and attitudes toward oral health
      among adult people with diabetes. Oral self-care was evaluated in the framework
      of the New Century model of oral health promotion. RESULTS: The proportion of
      edentulous subjects was 23%, and these were excluded from further analysis. Self
      reported twice-a-day brushing among dentate participants was significantly more
      common among women and the highly educated, but was less common compared with
      earlier studies among Finnish adults. A quarter of those surveyed reported never
      cleaning interdental surfaces, with the number of daily cleaners being nearly
      equal (27%). Age 40 years or over and recent treatment by a private dentist were
      significant predictors for daily interdental cleaning. The proportion of those
      who had attended a dental appointment within the last year was 63%, and the main
      reason for the last dental visit was an emergency among almost one-fifth of those
      surveyed. CONCLUSIONS: A need exists for further promotion of oral self-care
      among adults with diabetes. Support by dental and other health care professionals
      involved in diabetes care should be encouraged.

PMID- 12000346
TI  - Is medication a risk factor for dental caries among older people?
AB  - OBJECTIVES: This study examined the association between chronic medication
      exposure and 5-year dental caries increment among older people, using a
      theoretical model whereby xerogenic medication is thought to lead to increased
      caries by either (i) chronically lowering salivary flow, thus reducing salivary
      buffering of plaque acids, or (ii) producing the symptoms of dry mouth, leading
      to symptomatic relief through the use of cariogenic drinks and foodstuffs.
      METHODS: Data were obtained from participants remaining at the 5-year follow-up
      phase of a cohort study of community-dwelling South Australians aged 60 +.
      Medication information was available at baseline and at 5 years, enabling only
      those medications taken on both occasions to be included in the analyses. Dental
      examinations were conducted at baseline and 5 years, and a reversal-adjusted 5
      year caries increment was computed. Multivariate modelling was used to control
      the effects of potential confounders. RESULTS: Of the original sample, 528
      (62.3%) remained after 5 years, with those remaining tending to be younger,
      healthier and less medicated than those lost to follow-up. Five-year coronal
      caries incidence was 66.9%. The adjusted coronal caries increment (AdjCI) was
      higher among males and among those taking a beta-blocker or an antiasthma drug
      for the previous 5 years. The 5-year incidence of root surface caries was 59.3%.
      A lower root surface AdjCI was associated with taking daily aspirin. Of the
      medications shown in earlier analyses to predict dry mouth, only the antiasthma
      drugs were associated with higher caries experience, and they had predicted more
      severe xerostomia symptoms. CONCLUSIONS: This study offers no strong evidence for
      a medication-caries relationship, as only one of the observed medication-caries
      associations was explicable in terms of the theoretical model. However, it should
      be acknowledged that older people taking antiasthma drugs may be at higher risk
      of coronal caries, possibly through measures taken for the symptomatic relief of
      dry mouth.

PMID- 12000347
TI  - Dental fluorosis decline after changes to supplement and toothpaste regimens.
AB  - In 1989/90, in 659 12-year-olds in Perth (F 0.8 mg/L) and the Bunbury region of
      Western Australia (WA) (F approximately 0.25 mg/L), dental fluorosis prevalences
      were 40.2% and 33.0%. Fluoride supplements (OR 4.63) and extended residence in a
      fluoridated area (OR 4.06) were significant risk factors; toothpaste ingestion
      variables had ORs greater than unity; in 1990, DMFT for this age group was 0.84.
      School Dental Service took steps to discourage supplement and toothpaste
      ingestion and to promote low fluoride toothpaste for children < 6 years of age.
      OBJECTIVES: To evaluate the effect of this campaign on fluorosis and caries.
      METHODS: Between May-July 2000, 582 10-year-olds were examined for dental
      fluorosis (TF index) and dental caries (DMFT) in school dental clinics. RESULTS:
      Fluorosis prevalence was 22.2% in Perth and 10.8% in the Bunbury region. Overall
      prevalence was 18.0% and of this, 80.2% was TF 1, 17.9% was TF 2 and just 1.9%
      was TF 3. In 1989/90, 79 children had used supplements before the age of 4 year;
      in 2000 only 40 had done so (P < 0.001). Mean DMFT values in Perth and Bunbury
      were 0.32 and 0.28 (P > 0.05). Low F toothpaste, unavailable in 1989/90, had been
      used by 24.5%. The only significant risk factor was residence, OR 2.0.
      CONCLUSIONS: Fluorosis prevalence seems to have fallen in parallel with a
      reduction in discretionary intake from supplements and toothpaste. No increase in
      dental caries experience was recorded. Because the teeth examined in this study
      were at risk of fluorosis in 1992-95, very soon after policies changed, and
      because people are slow to change health habits, it seems reasonable to expect a
      further improvement when teeth mineralised in the late 1990s become visible.

PMID- 12000348
TI  - Development of a condition-specific quality of life measure for patients with
      dentofacial deformity: II. Validity and responsiveness testing.
AB  - The assessment of quality of life is becoming increasingly important in
      dentistry. This may be measured using two groups of instruments: generic and
      condition-specific. OBJECTIVES: This paper describes the processes of validity
      and responsiveness testing of a condition-specific quality of life measure for
      patients who present with severe dentofacial deformity requesting orthognathic
      treatment (the so-called Orthognathic Quality of Life Questionnaire). The
      development of the instrument is described in a previous paper. METHOD: The OQLQ
      was tested for validity using a visual analogue scale and also the Short-Form 36
      health survey questionnaire. Responsiveness was tested using longitudinal data
      obtained before, during and after orthognathic treatment. RESULTS AND
      CONCLUSIONS: The OQLQ shows good evidence of validity and responsiveness. This,
      together with previous evidence of good reliability, suggests that the instrument
      may prove useful in both clinical trials and in quality assurance.

PMID- 12000349
TI  - Oral health care education and its effect on caregivers' knowledge and attitudes:
      a randomised controlled trial.
AB  - OBJECTIVES: The effect of an oral health care education programme (OHCE) upon
      nursing home caregivers was assessed in a randomised controlled trial. METHODS: A
      self-administered questionnaire assessed oral health care knowledge and attitudes
      at baseline among 369 caregivers working in 22 nursing homes. Homes were randomly
      allocated to two groups. The intervention was a workplace OHCE. Caregivers
      assessed the value of the presentations. Questionnaires were re-administered 1
      month (time 2) and 6 months (time 3) after the OHCE was delivered. The knowledge
      and attitude score means of the groups were compared. Open-ended questions
      solicited qualitative data. RESULTS: Questionnaire response rates at the three
      time points ranged from 76.3% to 85.4%. Two-thirds of caregivers employed at the
      time of the intervention attended the presentations. The OHCE was favourably
      assessed in 79% of responses. The intervention group significantly improved their
      scores over the control group at times 2 and 3 for knowledge (P<0.003) and
      attitude (P<0.001). Analysed across both arms at baseline, the main predictors
      for knowledge and attitude scores were age and dental attendance pattern.
      Qualitative responses showed an acceptance of caregivers' roles in oral health
      care and criticism of existing provision within homes. CONCLUSIONS: The OHCE was
      well received and resulted in improved oral health care knowledge and attitudes.
      When viewed with separately reported trial results of clients' oral health
      status, knowledge and attitude score improvements coincided with improved
      delivery of oral health care.

PMID- 12000350
TI  - Childhood dental fear in the Netherlands: prevalence and normative data.
AB  - OBJECTIVE: This study aimed to present normative data on dental fear for the
      Dutch child population, by identifying not only highly fearful children but also
      children at risk for developing this high dental fear. METHODS: Fear distribution
      of samples of high and low fearful children was studied, using the Dutch parent's
      version of the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS).
      Total fear scores were calculated for both samples, for different age levels and
      for boys and girls separately. To establish cut-off scores, mean CFSS-DS scores
      were associated with dentists' clinical fear ratings and, in addition, were
      transformed into stanines. RESULTS: Scores between 32 and 38 were found to
      represent a borderline area for dental fear, and scores of 39 and higher to
      represent high dental fear. CONCLUSION: The results have shown 6% of the Dutch
      child population to be highly fearful, while another 8% may be at risk to develop
      high dental fear. By providing extra attention for these children, the
      development of high dental fear or phobia may be prevented.

PMID- 12000351
TI  - Socio-economic effect on caries. Incidence data among Swedish 12-14-year-olds.
AB  - OBJECTIVE: To assess whether socioeconomic factors are associated with the
      progression of caries, independently of a previous history of caries. SUBJECTS
      AND METHODS: In 1995, as part of a longitudinal study of preventive measures,
      3373 Swedish 12-year-olds were examined for caries and answered a questionnaire
      regarding socioeconomic level (SEL), ethnicity and residential area. The
      examination was repeated in 1997 when 3109 of the teenagers participated.
      Baseline caries and increments in the incidence of caries were computed. The
      influence of structural variables on baseline caries as well as a 2-year
      increment were analysed by means of Poisson regression. RESULTS: The risk of
      having caries as 12-year-olds was greater in workers' and immigrants' children,
      as well as in urban teenagers. The risk of developing new caries was most
      influenced by an earlier experience of caries. The social gradient was, however,
      still visible when a previous experience of caries was accounted for. The pattern
      found in the cross-sectional data from 1995, with more caries in children from
      workers' families, therefore prevailed in the increment data. CONCLUSION:
      Irrespective of earlier caries status there is a social gradient in caries
      progression. It therefore seems that the preventive methods do not function to
      the equal benefit of all children.

PMID- 12000352
TI  - Tobacco use and oral hygiene as risk indicators for periodontitis.
AB  - OBJECTIVE: To detect the periodontal status of male smokers and betel chewers in
      a rural community in Sri Lanka and compare it with that of male non-tobacco users
      of the same community. METHODS: A cross-sectional community based study was
      carried out in a sample of 2277 rural adult males aged 20-60 years, adopting
      multistage cluster sampling technique. The present analysis was confined to 2178
      subjects who were mutually exclusive smokers, betel chewers or non-tobacco users.
      The periodontal status was assessed by clinical measurement of levels of
      bacterial plaque (PLI), gingival inflammation (GI) and loss of epithelial
      attachment (LA). All measurements were carried out on four sites of all teeth
      present except third molars and the mean values for periodontal parameters were
      calculated. RESULTS: Bivariate analysis revealed that the overall periodontitis
      levels were significantly higher in betel chewers and smokers than in non-tobacco
      users. Multiple linear regression analysis showed that there were no significant
      effects of smoking and betel chewing per se on LA, independent of age,
      socioeconomic status (SES) and whether or not controlled for PLI. The effect of
      the quantified tobacco use on LA was statistically significant regardless of age,
      PLI or SES. However, the effect of the quantified tobacco use was considered
      limited when compared to that of oral hygiene. CONCLUSIONS: The findings
      highlighted the importance of oral hygiene in the aetiology of periodontitis
      while confirming the statistical significance of the quantified tobacco use on
      LA. Oral hygiene and the quantified tobacco use may be considered as risk
      indicators for periodontitis.

PMID- 12000353
TI  - Oral hygiene instructions and dietary sugar advice received by adolescents in
      1989 and 1997.
AB  - OBJECTIVES: The aim of this study was to find out how commonly adolescents
      receive oral hygiene instructions and dietary sugar advice in the Finnish public
      oral health care system and whether there have been any changes between 1989 and
      1997. METHODS: The data were collected as part of a nationwide research program,
      the Adolescent Health and Lifestyle Survey. Since 1977, a questionnaire has been
      sent every second year to a representative sample of 12-, 14-, 16- and 18-year
      old Finns eligible for free comprehensive oral health care. The sample size was
      3105 in 1989 and 8390 in 1997. RESULTS: Almost all adolescents (95-96%) had
      visited a dentist during the last 2 years. In all age groups, boys reported
      having received tooth cleaning instructions during their dental visit more often
      than girls did (40%/35%). There was only a minor decrease in instructions
      received between 1989 and 1997. Boys and those who brushed their teeth once a day
      or less often were the most likely to receive instructions in 1997. Only one
      fifth of adolescents reported having received dietary sugar advice, and there was
      a slight decrease between 1989 and 1997. In 1997, the groups of adolescents most
      likely to be advised were 12-16-year-old-boys, those using sweets daily and those
      living in Central Finland. CONCLUSIONS: Oral health instructions were only given
      to a minority of adolescents. The targeting of adolescents with health-damaged
      behavior is therefore important.

PMID- 12000354
TI  - Spatial analysis to identify differentials in dental needs by area-based
      measures.
AB  - OBJECTIVES: To examine the association between tooth decay and dental treatment
      needs in 5-12-year-old schoolchildren in Sao Paulo with area-level indicators of
      social development. METHODS: The present study refers to a representative sample
      of children from the city of Sao Paulo, Brazil, comprising 2491 girls and boys
      attending public and private schools in different areas of the city. The
      assessment of caries and treatment needs followed the international
      methodological standards prescribed by the World Health Organization. We used
      spatial data analysis to describe epidemiological measures distributed by small
      areas, and to explore hypotheses of ecological association between caries indexes
      and indicators of social development. RESULTS: Schoolchildren in central
      districts were less affected by tooth decay and presented fewer dental treatment
      needs when compared to those in peripheral deprived areas. At the spatial level,
      average family income, unemployment rate, household overcrowding, and an index of
      inequality of income distribution were significantly correlated with variables
      measuring children's caries experience. CONCLUSIONS: The heterogeneous
      distribution of caries indexes by areas of the city indicates higher levels of
      dental decay in areas of social deprivation. The delimitation of areas with
      increased risk of caries and greater dental treatment needs should be helpful to
      public health services for the formulation of policies and the targeting of
      resources to address these problems.

PMID- 12000355
TI  - Clinical outcomes of risk-based caries prevention in preschool-aged children.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes in young children of
      risk-based management of dental caries in comparison with routine prevention.
      METHODS: The study was carried out in two municipal health centers in Central
      Finland. The risk-based prevention group consisted of 299 children from Vanha
      Korpilahti, and the routine prevention group of 226 children from Saarijarvi. The
      children were 2 yr old at baseline, and they were followed up for 3 yr. All
      children received regular annual oral health care. In the risk-based prevention
      group, the presence of mutans streptococci (MS) in plaque (Dentocult-SM strip
      mutans -test, Orion Diagnostica, Espoo, Finland) and incipient caries lesions
      were the screening criteria. Additional prevention was targeted at MS-positive
      subjects twice a year, consisting of health education and application of fluoride
      varnish. For those who had incipient lesions, 'the high-risk category',
      additional prevention was given four times a year and this included also
      chlorhexidine varnish treatments. RESULTS: The screening and the preventive
      measures were successfully carried out by specially trained dental assistants.
      The proportion of children with cavitated caries or fillings was significantly
      lower in the risk-based than in the routine prevention group. The treatment
      effect was strongest within the high-risk category: two subjects had to be
      treated with intensive care for 3 yr to avoid restorative treatment of dental
      caries by the age of 5 yr in one subject (number needed to treat (NNT) = 2.0; 95%
      CI 1.4-3.8). The accuracy of screening was evaluated in the routine prevention
      group and found acceptable. CONCLUSIONS: The results indicate that in young
      children, risk-based management of caries seems practical, and prevention of
      caries can be targeted efficiently to individuals at risk.

PMID- 12000356
TI  - Psychological factors and perceptions of pain associated with dental treatment.
AB  - Although pain during dental treatment has been identified as playing a major role
      in the onset of dental anxiety and is a major concern of patients when seeking
      dental care, there have been very few studies of the prevalence of pain during
      dental treatment and the factors associated with patients' perceptions of pain.
      This study used data from a longitudinal population-based study to assess the
      proportion of dental attenders who experienced pain while having dental treatment
      and the psychological characteristics which predisposed them to experience pain.
      Of 1422 subjects who completed questionnaires at baseline and five-year follow
      up, 96.4% had visited a dentist over the observation period. Two fifths, 42.5%,
      reported having pain during treatment and one-fifth, 19.1%, had pain that was
      moderate to severe in intensity. Reports of pain were associated with the types
      of treatment received, and a number of baseline sociodemographic and
      psychological factors. In a logistic regression analysis predicting the
      probability of pain, a variable documenting the number of types of invasive
      treatment received (restorations, extractions, crowns/bridges, root canal therapy
      and periodontal treatment/surgery) had the strongest independent effect. Pain was
      also more likely to be reported by those with previous painful experiences and
      those who were anxious about dental treatment, expected treatment to be painful
      and felt that they had little control over the treatment process. Pain was less
      likely to be reported by those who said they were unwilling to accept or tolerate
      pain. Younger subjects and those with higher levels of education were more likely
      to report pain than older subjects and those with a lower educational level.
      These results indicate that pain is as much a cognitive and emotional construct
      as a physiological experience. They also have implications for dentists'
      behaviour when providing dental care.

PMID- 12000358
TI  - Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein, serum
      lipoprotein and glucose levels.
AB  - The present authors investigated the individual and combined associations of the
      apolipoprotein (apo) A-I -75 bp and +83 bp polymorphisms with plasma lipid,
      lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The
      frequency of the A allele at position -75 bp (G-->A) was 0.14 in women and 0.17
      in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C
      ->T and G-->A, respectively) were 0.04 and 0.05 in women and men, respectively.
      In women, the A allele was associated with significantly higher levels of apo B
      (P = 0.016), total cholesterol (TC) (P = 0.005), low-density lipoprotein
      cholesterol (LDL-C) (P = 0.018) and TC:high-density lipoprotein (HDL) ratio (P =
      0.026) compared to the G/G subjects. In men, no significant associations were
      detected between the -75 bp polymorphism and any lipid trait examined. The M2
      allele for the +83 bp polymorphism was significantly associated in men with
      higher levels of apo A-I (P = 0.002) and TC (P = 0.046). In women, a significant
      effect was observed for TC (P = 0.036), with M2+/- subjects having lower levels
      than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the
      apo A-I -75 bp and +83 bp polymorphisms was detected. Women carrying both rare
      alleles (G/A M2+/-) had significantly higher TC:HDL ratios (P = 0.031) compared
      to the other haplotypes. In men, significant differences were observed for apo A
      I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/- haplotype having
      the highest values compared to other genotype combinations. In conclusion, the 
      75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B,
      plasma TC and LDL-C in women, while the +83 bp polymorphism seems to affect the
      apo A-I levels in men, and the plasma cholesterol levels in both genders.

PMID- 12000359
TI  - Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous
      xanthomatosis.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare recessive autosomal disease caused
      by mutations of the sterol 27-hydroxylase gene. Clinically, CTX is characterized
      by tendon xanthomas, cataracts and progressive neurological deficits. Because of
      the disruption of the 27-hydroxylase activity, CTX patients have elevated plasma
      levels of cholestanol, a by-product of abnormal bile acid synthesis. The present
      authors describe a female patient with CTX. The proband in this study presented
      with elevated cholestanol levels, markedly reduced mitochondrial 27-hydroxylase
      activity and altered bile acid composition. The 27-hydroxylase gene was analysed
      for mutations by polymerase chain reaction amplification of the exons and the
      splice-junction regions of the gene. The proband was found to be a compound
      heterozygote for two different mutations which have not been previously
      described: (1) a G --> A transition at nucleotide 455 that is responsible for
      converting a glycine to a glutamic acid residue at amino acid position 112
      (G112E); and (2) a five-nucleotide deletion in exon 5 (from nucleotide 965 to
      969) that is responsible for a shift in the reading frame and the insertion of a
      premature codon at position 296, and consequently, the synthesis of a truncated
      protein lacking the heme-binding and andrenodoxin-binding domains. Long-term (18
      year) treatment of the proband with chenodeoxycholic acid (750 mg day-1) has been
      effective in preventing any progression of the disease.

PMID- 12000360
TI  - Identification and characterization of mutations underlying Sanfilippo syndrome
      type A (mucopolysaccharidosis type IIIA).
AB  - Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA; MPS IIIA) is caused
      by a deficiency of the lysosomal enzyme haparan N-sulphatase (NS). The genomic
      DNA segments of the NS gene from two Chinese patients with MPS IIIA were
      amplified by polymerase chain reaction, followed by DNA sequencing to study the
      molecular lesions. Four mutations (i.e. N42K, D235N, P293S and R377C) and five
      polymorphisms (i.e. IVS2-72A --> G, IVS2-26T --> C, IVS5+17C --> T, IVS5-37GC -->
      CTGT and R456H) were identified. Transfection of COS-7 cells with cDNA
      mutagenized to the corresponding mutations did not yield active enzyme,
      demonstrating the deleterious nature of the mutations. Western blot analysis
      revealed a 62-kDa precursor and 56-kDa mature forms for cells transfected with
      wild-type and polymorphic R456H enzymes. For cells transfected with mutant
      enzymes, the reduction in precursor and mature forms suggests an increased
      degradation of the mutant enzymes. The polymorphic DNA haplotype of the NS gene
      was analysed in 52 unrelated subjects. All five polymorphisms were in Hardy
      Weinberg equilibrium. The strong non-random association among the five
      polymorphisms suggests little or no recombination in the NS gene.

PMID- 12000361
TI  - A familial cryptic subtelomeric deletion 12p with variable phenotypic effect.
AB  - A 15-year-old-boy and his mother, both carrying a cryptic deletion within
      12p13.33, are described. The proband has a mild phenotype with moderate mental
      retardation and severe behavioural problems. The mother had some learning
      difficulties at school. Conventional GTL-banded high-resolution chromosome
      analysis showed normal karyotypes. Subsequent analysis by fluorescence in situ
      hybridization using a set of probes specific for the subtelomeric regions of all
      chromosomes, plus a series of probes at 12p13.33 extending from the 12p telomere,
      showed that both mother and son carry a 1.65 Mb terminal deletion in this region.
      There are 10 predicted genes within the deleted region. The unanticipated
      familial nature of the deletion emphasizes the value of family studies in all
      cases with subtelomeric abnormalities. It also demonstrates the difficulty in
      making a clinical diagnosis of individuals with this deletion. To the best of the
      present authors' knowledge, the proband and his mother are the first patients
      described with a submicroscopic deletion at 12p13.33.

PMID- 12000362
TI  - De novo supernumerary ring chromosome 7: first report of a non-mosaic patient and
      review of the literature.
AB  - The present authors report the case of a 12-year-old-boy with a de novo, non
      mosaic supernumerary ring chromosome 7 associated with significant developmental
      delay and speech difficulty. A review of the literature identified a total of 18
      cases with ring chromosomes 7 who can be classified into two groups: (1) patients
      with a cell line that has 47 chromosomes with a small supernumerary ring
      chromosome 7 resulting in partial trisomy; and (2) individuals had a cell line
      with a large ring chromosome replacing one of the normal chromosomes 7 resulting
      in partial monosomy. A comparison of clinical features in the two groups of
      patients showed several common features such as growth and mental retardation,
      and facial dysmorphism, including, ear and eye anomalies. However, patients with
      partial trisomy have speech difficulty as a distinguishing feature, while
      patients with partial monosomy have skin lesions as a cardinal feature. All the
      published cases of ring chromosome 7, irrespective whether they are supernumerary
      or normal modal number, are mosaics except for one. The present subject is the
      first case of a de novo, non-mosaic supernumerary ring chromosome 7.

PMID- 12000363
TI  - Complete screening of the CFTR gene in Argentine cystic fibrosis patients.
AB  - In order to establish the nature and the distribution of mutations causing cystic
      fibrosis (CF) in 220 unrelated Argentine families, the present authors conducted
      an extensive molecular analysis of the CF transmembrane regulator (CFTR) gene.
      First, a direct mutation analysis of 13 common mutations was done, enabling the
      detection of 319 out of 440 CF alleles (72.52%). Then an exhaustive screening of
      the entire coding region and the adjacent sequences of the CFTR gene was
      performed in all patients carrying at least one unidentified CF allele using the
      multiplex heteroduplex analysis assay followed by direct DNA sequencing. Thirty
      nine different CF mutations, including five previously undescribed mutations
      (i.e. L6V, Y362X, 1353insT, 2594delGT and 2686insT) and two novel polymorphisms
      (i.e. 1170G/C and 3315A/C) were identified. As a result, the overall detection
      rate increased by up to 83.45%. Besides DeltaF508, only five mutations showed
      frequencies higher than 1%. In addition, a total of 49% of the mutations were
      rare because they were found in only one CF family. This wide spectrum of CF
      mutations is in agreement with the heterogeneous ethnic origin of the Argentine
      population. The data obtained here may have important consequences for the
      development of adequate strategies for the molecular diagnosis of CF in
      Argentina.

PMID- 12000364
TI  - Familial adenomatous polyposis in two Black South African families.
AB  - The apparent low incidence of colon cancer in the Black population of South
      Africa has been ascribed to a non-Western diet. The present authors report the
      identification of two common 5-bp deletions at codons 1309 and 1061 of the
      adenomatous polyposis coli (APC) gene in a Xhosa and Zulu patient, respectively.
      The in vitro transcription/translation test (PTT) and a non-radioactive
      heteroduplex method, which facilitates resolution of enzymatically amplified DNA
      by agarose gel electrophoresis, were used for mutation detection. This study
      represents the first report of APC mutations in indigenous Black individuals
      clinically diagnosed with familial adenomatous polyposis coli (FAP). The two
      deletion mutations are responsible for FAP in 35% of affected South Africans, a
      frequency similar to that described in several other non-African populations. The
      apparently low incidence of colon cancer in the African population may be
      ascribed either to the rare occurrence of the 'second hit' needed for polyp
      formation or to a lower incidence of mutations in the APC gene.

PMID- 12000365
TI  - Mutation in the FGFR2 gene in a Taiwanese patient with Beare-Stevenson cutis
      gyrata syndrome.
AB  - The present authors report the first case of Beare-Stevenson syndrome in Taiwan.
      The patient shares several clinical characteristics of Beare-Stevenson syndrome
      such as cutis gyrata, cloverleaf skull, prominent eyes, cleft palate, ear defects
      and a protruding umbilical stump. Molecular genetic analysis of the FGFR2 gene in
      this patient's DNA revealed a missense A --> G mutation on nucleotide 1303 of the
      FGFR2 cDNA. This mutation leads to a Tyr --> Cys substitution at residue 375
      located at the N-terminal end of the transmembrane domain of FGFR2. The present
      results are in accordance with other previously published reports and strengthen
      the importance of the FGFR2 gene in the pathogenesis of Beare-Stevenson syndrome.

PMID- 12000366
TI  - An exonic mutation of the GH-1 gene causing familial isolated growth hormone
      deficiency type II.
AB  - A heterozygous base change was identified in exon 3 of the growth hormone (GH)-1
      gene in a Japanese family with autosomal dominant GH deficiency. All of the
      patients from this family had a heterozygous G to T transversion at the first 5'
      site nucleotide of exon 3. Analysis of the GH-1 cDNA, synthesized from
      lymphoblasts of the patients, revealed an abnormal shorter transcript as well as
      a normal-sized transcript. Direct sequencing of this abnormal transcript showed
      that the transcript completely lacked exon 3. In familial isolated GH deficiency
      (IGHD) type II, several heterozygous mutations have been reported at the donor
      splice site in intron 3 of the GH-1 gene or inside intron 3, which causes
      aberrant GH messenger RNA splicing, resulting in the deletion of exon 3. This
      deletion causes a lack of amino acid residues 32-71 in the mature GH protein.
      This mutant GH is well-known to exert a dominant negative effect on the secretion
      of mature normal GH protein. Thus, in the subject family, a heterozygous G-to-T
      transversion at the first nucleotide of the exon 3 deletes exon 3 in mature GH
      mRNA and causes GH deficiency. The present authors suggest that the first
      nucleotide of exon 3 is critical for the splicing of GH-1 mRNA.

PMID- 12000367
TI  - A 4q21-q22 deletion in a girl with severe growth retardation.

PMID- 12000368
TI  - Identification of two novel mutations, L105R and C342R, in Type I Gaucher
      disease.

PMID- 12000369
TI  - Skin cancer screening and surveillance.

PMID- 12000370
TI  - Guidelines for dosimetry and calibration in ultraviolet radiation therapy: a
      report of a British Photodermatology Group workshop.
AB  - This report examines the dosimetry of ultraviolet (UV) radiation applied to
      dermatological treatments, and considers the definition of the radiation
      quantities and their measurement. Guidelines are offered for preferred
      measurement techniques and standard methods of dosimetry. The recommendations
      have been graded according to the American Joint Committee on Cancer
      classification of strength of recommendation and quality of evidence (summarized
      in Appendix 5).

PMID- 12000371
TI  - Low-dose dithranol treatment and tape stripping induce tolerance to dithranol in
      a mouse ear oedema model.
AB  - BACKGROUND: It is well known from clinical practice that repeated treatment with
      dithranol leads to the development of tolerance. OBJECTIVES: To investigate the
      characteristics and mechanism of such dithranol tolerance. METHODS: The mouse ear
      was pretreated with a low dose of dithranol or croton oil or, in previously
      sensitized animals, with dinitrofluorobenzene (DNFB). Twenty-four hours later
      irritant dermatitis was elicited by painting the mouse ear with a high dose of
      dithranol, croton oil or DNFB, and the dermatitis was characterized by
      measurement of ear thickness. RESULTS: Low-dose dithranol significantly
      suppressed dithranol-induced oedema, whereas it had no effect on croton oil- or
      DNFB-induced dermatitis, suggesting that dithranol-induced tolerance is specific.
      Tolerance to dithranol could not be induced by pretreatment of the mouse ear with
      a low dose of croton oil or DNFB. Mild tape stripping of the mouse ear also
      inhibited the inflammatory effect of dithranol applied 24 h later. Superoxide
      dismutase treatment abolished the tolerance-inducing effect of low-dose dithranol
      or stripping. CONCLUSIONS: These results suggest that superoxide anion radicals
      are involved not only in the inflammatory effect of dithranol, but also in the
      induction of tolerance.

PMID- 12000372
TI  - Impact of anatomical location on barrier recovery, surface pH and stratum corneum
      hydration after acute barrier disruption.
AB  - BACKGROUND: It is not known whether distinct anatomical locations will respond
      with different recovery rates following acute barrier challenges. OBJECTIVES: To
      investigate whether barrier parameters differ at five body sites during recovery
      from acute disruption. METHODS: Acute barrier disruption was achieved by tape
      stripping and by acetone extraction of stratum corneum lipids. Transepidermal
      water loss (to assess barrier function), capacitance (for stratum corneum
      hydration) and skin surface pH were measured at each of five different body sites
      in 14 human volunteers. Individual measurements were obtained every 24 h for 96
      h. RESULTS: Lipid-rich skin areas (e.g. the forehead) were the most vulnerable to
      barrier disruption by either method. While acetone treatment affected barrier
      function and decreased stratum corneum hydration, tape stripping similarly
      altered barrier function but increased capacitance values. Although the effect of
      barrier disruption on surface pH appeared to vary with location, no significant
      pattern of variation emerged. Independent of the method used for barrier
      disruption, the pH normalized within 96 h. CONCLUSIONS: Skin at different body
      sites shows distinct patterns of barrier recovery that are likely to be related
      to structural and physiological differences. Therefore, 'anatomically specific'
      regimens appear possible and relevant for the treatment of cutaneous disorders.
      In addition, adequate statistical analyses are essential to detect real
      differences in barrier recovery parameters.

PMID- 12000373
TI  - Proteomic analysis of skin irritation reveals the induction of HSP27 by sodium
      lauryl sulphate in human skin.
AB  - BACKGROUND: There is an increasing need for screening of mild irritants in vitro
      to reduce animal testing. OBJECTIVES: Proteomics were used to search for new
      markers of which the expression changes after mild irritation. METHODS: Sodium
      lauryl sulphate (SLS) was applied topically on excised human skin. Epidermal
      proteins were isolated from SLS-treated skin specimens that showed hardly any
      morphological changes. The proteins were analysed by two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) and proteins that significantly
      increased or decreased after SLS treatment in a dose-dependent way were
      characterized by mass spectrometry. Subsequently, immunohistochemistry was
      performed on skin samples treated with SLS in vivo and nonanoic acid (NAA) or
      benzalkonium chloride (BC) in vitro to evaluate one of the identified proteins
      for its predictive value. RESULTS: We identified seven proteins as potentially
      new epidermal markers for skin irritation. Among these seven proteins, the 27 kDa
      heat shock protein (HSP27) was identified as the most prominently upregulated
      protein. A strong nuclear HSP27 staining was seen in the SLS-treated skin,
      whereas in the vehicle controls only cytoplasmic staining was observed. Moreover,
      nuclear staining was also observed after topical application of SLS in vivo and
      after exposure to NAA and BC in vitro. CONCLUSIONS: Our findings suggest that
      HSP27 may serve as a sensitive marker of skin irritation and eventually as a
      novel tool in clinics for testing the sensitivity of the patient for a panel of
      irritants.

PMID- 12000374
TI  - p53-dependent regulation of heat shock protein 72.
AB  - BACKGROUND: p53 is a key regulator of the cellular stress response. p53 modulates
      the transcription of several genes. OBJECTIVES: To examine the influence of p53
      on expression of heat shock protein 72 (HSP72). METHODS: Two model systems were
      used. (i) HSP72 expression was studied by Western blot on extracts from p53
      proficient or p53-deficient primary mouse keratinocytes, and (ii) archival human
      anogenital skin from fibroepithelial polyps, human papillomavirus (HPV) 16/18
      associated lesions or squamous cell carcinomas (SCCs) was subjected to
      immunostaining for HSP72. RESULTS: Basal HSP72 expression was higher in
      keratinocytes from p53-deficient than from p53-proficient mice. Immunostaining
      for HSP72 was higher in HPV 16/18 lesions and SCCs, which have reduced p53
      protein. CONCLUSIONS: p53 status may influence the basal level of HSP72.

PMID- 12000375
TI  - Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: a
      randomized, double-blind, placebo-controlled study of histamine and other
      inducers of itch.
AB  - BACKGROUND: Investigations of pruritogenic substances in humans have involved
      intradermal injections in normal skin; itching of inflamed skin has been little
      studied. OBJECTIVES: To develop an itch model with provocation of itch in
      experimentally inflamed skin as well as in normal skin, using subjects as self
      controls. METHODS: In 32 non-atopic volunteers aged 21-30 years, the skin of five
      selected test sites on one volar forearm was pretreated for 24 h with large Finn
      chambers containing 1% sodium lauryl sulphate (SLS) used as a standard contact
      irritant to induce inflammation. Twenty microlitres of different pruritogenic
      substances [histamine, substance P, neurokinin A, neurokinin B, trypsin, platelet
      activating factor (PAF) and serotonin] and saline as control were injected
      intradermally into the inflamed test sites and in corresponding non-treated sites
      on the opposite forearm. The test individuals scored itch intensity on a visual
      analogue scale for 20 min, and weal area was then measured. : RESULTS: Histamine
      and substance P induced itch in both normal and inflamed skin compared with a
      saline reference. Neurokinin A, trypsin, PAF and serotonin only elicited itch in
      normal skin, and neurokinin B neither elicited itch in normal skin nor in
      inflamed skin. Itch was induced in normal and SLS-inflamed skin to a similar
      magnitude. However, weal area after histamine was significantly (P < 0.001)
      larger in inflamed skin when compared with normal skin. CONCLUSIONS: Histamine
      and substance P elicited itch to the same degree in normal skin and inflamed skin
      pretreated with SLS despite a stronger weal response in inflamed skin. Mediators
      present in inflamed skin did not potentiate itch, a c-fibre-mediated neuronal
      response. The weal reaction is based on enhanced vascular permeability (protein
      extravasation). A greater skin perfusion in inflamed skin may therefore have
      increased the weal size. We propose an experimental model in humans for testing
      of itch involving both normal and inflamed skin. The model has the potential for
      use in evaluating new topical and systemic treatments of itch.

PMID- 12000376
TI  - Upregulation of epidermal surface molecule expression in primary and ultraviolet
      induced lesions of lupus erythematosus tumidus.
AB  - BACKGROUND: Lupus erythematosus tumidus (LET), a photosensitive skin disorder
      with characteristic clinical and histological features, has not been generally
      accepted as a subset of cutaneous lupus erythematosus (CLE). OBJECTIVES: To
      analyse the expression of epidermal surface molecules in skin biopsy specimens
      from patients with LET and to relate the results to other variants of CLE, such
      as discoid lupus erythematosus (DLE) and subacute CLE (SCLE). METHODS: In total,
      45 patients with different subtypes of CLE were included in the study, and
      cryostat sections from primary and ultraviolet (UV) A- and UVB-induced skin
      lesions were investigated using immunohistochemical methods. RESULTS: In contrast
      to healthy controls, skin lesions of LET showed upregulation of intercellular
      adhesion molecule-1 (ICAM-1) and histocompatibility class II molecules (HLA-DR),
      with an expression pattern resembling that seen in DLE and SCLE. Furthermore,
      staining with a monoclonal antibody against 27E10, a distinct marker for cell
      activation and differentiation, revealed intense focal or band-like labelling of
      all epidermal layers independent of the type of lesion. CONCLUSIONS: Expression
      of epidermal surface molecules such as ICAM-1, HLA-DR and 27E10 is equally
      upregulated in primary and UV-induced lesions of patients with LET, DLE and SCLE.
      These results support our recent clinical findings that LET represents a distinct
      subset of CLE with a similar immunopathomechanism rather than a different
      disease.

PMID- 12000377
TI  - Inflammation is associated with progression of actinic keratoses to squamous cell
      carcinomas in humans.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) is a common skin tumour that may
      metastasize and lead to death. We have observed that before actinic keratoses
      (AK) progress to SCCs they may become tender and inflamed. In some of these,
      histological examination shows that they are, in fact, SCCs. OBJECTIVES: To study
      the progression of AK to SCCs. METHODS: We studied skin tumours from 50 patients
      with either asymptomatic AK, inflamed AK or SCCs, using immunocytochemistry. The
      diagnosis of each tumour was confirmed by histological examination. RESULTS:
      Studies of differentiation using heat shock protein 27 showed a stepwise loss of
      differentiation as the tumours progressed from asymptomatic AK, through inflamed
      AK to SCCs. During the inflamed AK phase, there was a marked increase in T
      lymphocytes and Langerhans cells: the number of infiltrating cells diminished as
      progression to SCC occurred. There was an increase in immunoreactive p53 and the
      apoptosis inhibitor bcl-2 as tumours progressed from AK to SCCs, and a decrease
      in Fas and Fas ligand. CONCLUSIONS: These studies have shown that progression
      from benign to malignant tumours may be associated with an inflammatory response,
      which appears to drive malignant conversion, but subsides rapidly following this
      conversion.

PMID- 12000378
TI  - A randomized, double-blind, parallel-group, duration-finding study of oral
      terbinafine and open-label, high-dose griseofulvin in children with tinea capitis
      due to Microsporum species.
AB  - BACKGROUND: Tinea capitis, a common clinical pattern of dermatophyte infection in
      children is becoming a public health hazard in some countries. Several studies
      have reported terbinafine to be a safe and well-tolerated fungicidal drug for the
      treatment of this infection. However, the optimal treatment duration for its use
      in the treatment of tinea capitis caused by Microsporum species has not yet been
      determined. OBJECTIVE: (i) To establish the optimal duration for terbinafine
      treatment to bring about complete cure of tinea capitis due to Microsporum
      infection in a large paediatric population, and (ii) to obtain information on the
      maximum therapeutic effect of the existing therapy. PATIENTS AND METHODS: This
      parallel-group, double-blind, multicentre study was conducted in Europe and South
      America. Patients were randomized to one of four oral terbinafine treatment arms
      (6, 8, 10 or 12 weeks treatment) or to an open label, 12-week, high-dose
      griseofulvin (20 mg x kg(-1) x day(-1)) arm at a 1 : 1 : 1 : 1 : 1 ratio. All
      patients were followed up for 4 weeks after the end of the treatment phase.
      RESULTS: In this group of 134 intention-to-treat patients, effective treatment
      was observed at the end of study in 62% of patients treated with terbinafine for
      6 weeks and in 63% treated for 8 weeks. Mycological cure was obtained in 59% and
      57%, respectively, and clinical cure in 76% and 80%. In the griseofulvin group,
      effective treatment was 88%, mycological cure was 76% and clinical cure 96%.
      However, these high rates were believed to be due to the high dosage of this drug
      and the prolonged course of treatment. Complete cure was observed at the end of
      study in 62% patients treated with terbinafine for 6 weeks, in 60% treated for 8
      weeks and in 84% patients treated with griseofulvin for 12 weeks. CONCLUSIONS:
      Although there was no statistical trend between the duration of terbinafine
      treatment within the groups for complete cure at the end of study, there was a
      positive correlation between the daily dose of terbinafine (mg x kg(-1)) and
      complete cure. Terbinafine therapy for 6 weeks could represent an alternative to
      griseofulvin for the treatment of Microsporum tinea capitis. However, further
      clinical trials are required in order to optimize the dose regimen to allow
      higher cure rates to be reached.

PMID- 12000379
TI  - Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial.
AB  - BACKGROUND: Skin-homing, memory T lymphocytes play an important role in the
      pathogenesis of psoriasis by interacting with the vascular addressin, E-selectin
      and trafficking into lesional skin. Thus an attractive option for targeted
      therapy of the disease would be blockade of skin-homing T cells with an antibody
      directed at E-selectin. OBJECTIVE: We performed a multicentre, randomized,
      placebo-controlled trial to investigate the clinical efficacy and side-effect
      profile of a humanized monoclonal antibody to E-selectin, CDP850, in the
      treatment of moderate to severe chronic plaque psoriasis. METHODS: Patients with
      moderate/severe chronic plaque psoriasis were selected for study. Nine male
      subjects (mean age 37 years, range 25-47) were given 20 mg kg-1 CDP850
      intravenously as a single dose and four subjects (three males, one female; mean
      age 40 years, range 23-50) received placebo infusion. Clinical response to
      treatment was assessed using the psoriasis area and severity index (PASI). Skin
      biopsies were taken for immunohistochemical analysis at the baseline,
      pretreatment, visit and also at day 2 and weeks 1 and 4 postinfusion. RESULTS:
      The treatment was well-tolerated with a minimal side-effect profile. Plasma E
      selectin levels were significantly decreased in those subjects who received
      CDP850 compared with those who had placebo for the entire study period. At the
      end of study (8 weeks postinfusion), there was no significant reduction in PASI
      from baseline for either the CDP850 or placebo-treated groups.
      Immunohistochemical analysis of biopsies taken from lesional psoriatic skin
      showed that 2 days after dosing with CDP850, staining for E-selectin was
      decreased, although not absent, on dermal vascular endothelial cells when
      compared with baseline (P < 0.01). This decrease in E-selectin expression was
      maintained 4 weeks after infusion (P < 0.05). It was not, however, accompanied by
      a significant reduction in numbers of neutrophils or lymphocytes in the dermis.
      There was a statistically significant increase in CD1a-positive epidermal
      Langerhans cells compared with pre-dose levels at week 1 (P < 0.05). CONCLUSIONS:
      This clinicopathological study shows that anti-E-selectin (CDP850), although a
      well-tolerated, logical and safe therapy, does not appear to possess a
      therapeutic role in the treatment of chronic plaque psoriasis.

PMID- 12000380
TI  - Serum S100 concentrations are not useful in predicting micrometastatic disease in
      cutaneous malignant melanoma.
AB  - BACKGROUND: S100 protein is an acidic calcium binding protein that is expressed
      by melanoma cells. Elevated serum values of S100 have been described in
      metastatic disease and it has been suggested that it may be used as an adjunct to
      staging and monitoring of treatment. Micrometastatic disease in the sentinel
      lymph node can be demonstrated by sentinel node biopsy (SNB) and the sentinel
      node status is known to be the most important predictor of relapse. OBJECTIVES:
      To determine whether serum S100 concentrations could predict the presence of
      micrometastatic disease. METHODS: Thirty-one patients with primary cutaneous
      melanoma > 1 mm were recruited from referrals to the Melanoma clinic. All
      patients had serum S100 concentrations evaluated prior to undergoing SNB. Serum
      S100 concentrations were established using an immunoluminometric method. Sentinel
      nodes were identified using a dual technique with both radiolabelled colloid
      (residual from preoperative lymphoscintigraphy) and blue dye according to the MD
      Anderson Cancer Center protocol. Results Nine of these 31 patients had evidence
      of micrometastatic disease on SNB. The mean serum S100 concentration of those
      with positive SNBs was 0.027 microg L-1 compared with 0.045 microg x L(-1) in
      patients with negative SNBs (normal < 0.14 microg x L(-1)). No patient in the
      study demonstrated raised concentrations of serum S100. CONCLUSIONS: We conclude
      that serum S100 concentrations do not predict the presence of micrometastatic
      melanoma in sentinel nodes in primary cutaneous melanoma.

PMID- 12000381
TI  - Nail involvement in pemphigus vulgaris.
AB  - BACKGROUND: Involvement of the nail unit in pemphigus vulgaris (PV) is thought to
      be rare. OBJECTIVES: To determine the frequency of nail changes among patients
      with PV. METHODS: Nail changes were recorded in patients with PV and were
      analysed retrospectively. Biopsies were taken from the nail bed and nail matrix
      for histological and immunofluorescence observations. Microscopic (potassium
      hydroxide) examination and fungal culture were performed. RESULTS: Nail changes
      were present in 30 of 64 (47%) patients with PV. Sixteen patients had
      onychomycosis and 14 had nail changes due to PV. These included onychomadesis,
      discoloration, deformity, onychorrhexis, onycholysis, subungual haemorrhage,
      subungual hyperkeratosis and paronychia. Onychomycosis affected fingernails and
      toenails, but changes due to PV occurred only in fingernails, most commonly on
      the thumb and index finger. No connection was found between the patient's
      occupation and nail involvement, and there was no correlation with the severity
      or duration of PV. In a control group of 64 patients of similar sex and age, only
      two had non-specific fingernail changes. CONCLUSIONS: Nail changes in PV may be
      more frequent than previously thought.

PMID- 12000382
TI  - Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients:
      10-year surveillance data and snapshot distribution study.
AB  - BACKGROUND: Cutaneous propionibacteria are implicated in acne pathogenesis,
      although their exact role in the genesis of inflammation is still poorly
      understood. Agents, including antibiotics, that reduce the numbers of
      propionibacteria on skin are therapeutic. Resistance in the target organism is a
      well-recognized consequence of antibiotic therapy for acne but formal prevalence
      and distribution data are lacking. OBJECTIVES: To monitor the prevalence of skin
      colonization by antibiotic-resistant propionibacteria in acne patients attending
      the dermatology out-patient clinic at Leeds General Infirmary over a 10-year
      period beginning in 1991, and to examine the distribution of resistant strains on
      acne-prone skin and in the nares. METHODS: Propionibacterial samples were
      obtained from the skin surface of the worst affected site (usually the face) of
      4274 acne patients using a moistened swab. The swab was used to inoculate agar
      plates with and without selective antibiotics. After anaerobic incubation at 37
      degrees C for 7 days, the amount of growth in the presence of each antibiotic was
      scored on a scale from 0 to 5+. A small number of patients (72) were selected for
      more detailed quantitative sampling at six different sites to examine the
      distribution of resistant propionibacteria on acne-prone skin and in the anterior
      nares. RESULTS: The proportion of patients carrying strains resistant to one or
      more commonly used antiacne antibiotics rose steadily from 34.5% in 1991 to a
      peak of 64% in 1997. The prevalence dropped to 50.5% during 1999 and then rose
      again to 55.5% in 2000. Resistance to erythromycin was the most common and the
      majority of erythromycin-resistant strains were cross-resistant to clindamycin.
      Resistance to tetracyclines was less common in all years and with little increase
      over time. The more detailed quantitative study in 72 patients showed that
      population densities of resistant propionibacteria varied considerably between
      sites and between individuals. Almost invariably, patients were colonized with
      resistant strains at multiple sites, including the nares. CONCLUSIONS: Skin
      colonization with antibiotic-resistant propionibacteria is much more common now
      than a decade ago. Resistant propionibacteria are widely distributed on acne
      prone skin and in the nares. This suggests that they will be very difficult to
      eradicate using existing therapeutic regimens, especially from the nasal
      reservoir.

PMID- 12000383
TI  - Skin irritation thresholds in hairdressers: implications for the development of
      hand dermatitis.
AB  - BACKGROUND: Individuals vary in their ability to react to irritants. OBJECTIVES:
      To observe the development of clinical hand dermatitis and sensitization
      prospectively in trainee hairdressers and to compare this with their irritant
      threshold to sodium lauryl sulphate (SLS). METHODS: Subjects were patch tested to
      a limited series of occupational importance and their irritant threshold to SLS
      was determined; patch testing was repeated 6 months later and subjects were
      assessed for hand dermatitis. RESULTS: The development of hand dermatitis was
      associated with a lower irritant threshold. A similar association was not found
      for sensitization. CONCLUSIONS: The development of clinical dermatitis in
      prospectively followed subjects with greater irritant reactivity has not
      previously been identified. The association of greater irritant reactivity with a
      proinflammatory cytokine polymorphism may partly explain this. Further
      development of the irritant threshold test could contribute to the identification
      of non-atopic subjects at risk of occupational skin disease.

PMID- 12000384
TI  - In vitro/in vivo correlations between transdermal delivery of 5-aminolaevulinic
      acid and cutaneous protoporphyrin IX accumulation and effect of formulation.
AB  - BACKGROUND: Photodynamic therapy (PDT) using topical application of 5
      aminolaevulinic acid (ALA) has been widely reported for the treatment of a
      variety of neoplastic and non-neoplastic cutaneous diseases. Although different
      formulations containing variable amounts of ALA have been applied in PDT, the
      dose-response relationships between transdermal ALA delivery and cutaneous
      protoporphyrin IX (PpIX) accumulation have not been studied. OBJECTIVES AND
      METHODS: The objectives of this study were to investigate the effect of
      permeability barrier function, ALA concentration and formulation on the in vitro
      penetration of ALA through nude mouse skin and cutaneous PpIX formation at 2 h
      following a 2-h application of ALA to nude mouse skin in vivo, and to delineate
      the relationships in between. RESULTS: Results demonstrated that variations in
      barrier integrity, in addition to ALA concentration, profoundly influenced ALA
      delivery to generate PpIX. Saturable correlations were found to exist between
      PpIX concentrations in both the epidermis and dermis in vivo and its transdermal
      flux in vitro, and the relationships were well described by the Emax model. The
      established correlations based on pure aqueous solutions were applicable to
      different formulations containing hydroxypropylmethylcellulose as the gelling
      agent and ethylenediamine tetraacetic acid as the iron chelator. Moreover,
      incorporation of desferrioxamine, another iron chelator, in the formulation
      prolonged cutaneous PpIX accumulation in the skin in comparison with 3% ALA
      aqueous solution, but the peak PpIX levels were not increased. Application of a
      liposomal formulation resulted in similar prolongation in ALA-induced PpIX
      accumulation, as well as better epidermal targeting. CONCLUSIONS: Knowledge of
      the dose-response relationships and the effect of formulation is important for
      designing optimal formulations and treatment schedules for topical ALA-PDT.

PMID- 12000385
TI  - Laser-induced weal and flare reactions: clinical aspects and pharmacological
      modulation.
AB  - BACKGROUND: Among the adverse effects of cutaneous laser therapy, weal and flare
      reactions immediately after treatment have received little attention, and the
      pathomechanisms are unclear. OBJECTIVES: To study clinical features and possible
      mechanisms of laser-induced weal and flare reactions in order to identify means
      of possible therapeutic intervention. METHODS: Normal skin from the inner arm of
      20 volunteers was treated with an argon laser, and the size of weal and flare
      reactions was measured over a 60-min period. Skin biopsies were taken from four
      volunteers before and up to 24 h after laser treatment and examined
      histologically and immunohistologically. Possible underlying mechanisms were also
      explored using various topical or systemic pharmacological agents. RESULTS:
      Wealing was noted in 19 of 20, and flare reactions in all volunteers, with peak
      values at 15 min. Skin biopsies showed central coagulation of the tissue, cleft
      formation between epidermis and dermis, normal numbers of morphologically intact
      mast cells on toluidine blue staining close to the lesion, and only minor
      upregulation of endothelial and leucocyte adhesion molecules. In agreement with
      these findings, pretreatment with acetylsalicylic acid, the H1-blocker loratadine
      and triamcinolone cream was ineffective or resulted in a non-significant
      reduction of weal and flare reactions. In contrast, local anaesthetics as well as
      neuropeptide depletion of skin with capsaicin abolished the reactions almost
      completely. CONCLUSIONS: Transient weal and flare reactions in response to laser
      treatment occur in almost all persons and are based primarily on a neurogenic
      rather than a histamine- or mast cell-dependent mechanism.

PMID- 12000386
TI  - The value of lymphocytopenia as a marker of systemic involvement in cutaneous
      lupus erythematosus.
AB  - BACKGROUND: Some patients suffering from cutaneous lupus erythematosus (CLE)
      develop extracutaneous manifestations during the course of the disease: up to 5%
      of patients with discoid LE (DLE) and up to 30% of subacute cutaneous LE (SCLE)
      patients show systemic involvement. Recent studies revealed some markers
      indicating systemic manifestations of CLE patients. However, the significance of
      diminished peripheral lymphocyte numbers as a marker of systemic involvement in
      CLE has not been investigated before. OBJECTIVES: To determine the value of
      lymphocytopenia (< 1500 cells microL(-1)) as a marker of extracutaneous
      manifestations in CLE patients. : Methods The records of 72 CLE patients (44 DLE;
      28 SCLE) were investigated. Systemic involvement was defined in accordance with
      the criteria of the European Academy of Dermatology and Venereology. Analyses of
      peripheral lymphocyte numbers were done by fluorescence-activated cell sorter
      analysis. RESULTS: Five CLE patients developed extracutaneous manifestations
      during the course of disease. All these patients were lymphocytopenic.
      Differences between peripheral lymphocyte numbers of CLE patients with and
      without additional systemic involvement were highly significant (P < 0.01).
      CONCLUSIONS: Our results suggest that lymphocytopenia in patients with CLE is a
      high sensitive but low specific marker of systemic involvement.

PMID- 12000387
TI  - Long-term prognosis of patients treated for erythema migrans in France.
AB  - BACKGROUND: The long-term prognosis of patients treated for erythema migrans has
      only rarely been assessed. OBJECTIVES: To evaluate the clinical characteristics
      and long-term prognosis of patients treated for erythema migrans in the region of
      Alsace, France. METHODS: In a prospective study, 56 consecutive patients
      presenting with erythema migrans at the Strasbourg University Hospital between
      1995 and 1999 were examined and a Borrelia burgdorferi enzyme immunoassay was
      performed. Patients were treated with tetracyclines or amoxycillin. Patients were
      re-examined 6 weeks later and a telephone interview was performed in summer 2000
      to evaluate the long-term outcome. RESULTS: There were 25 women and 31 men of
      mean age 49 years presenting with single (n = 54) or multiple (n = 2) erythema
      migrans lesions. At the time of diagnosis, 30% of the patients had systemic
      signs, myalgias or arthralgias and only 36% of 50 patients were seroreactive
      against B. burgdorferi. None of the 51 patients evaluated at 6 weeks and none of
      the 37 patients interviewed after a median delay of 3 years had developed
      complications attributable to Lyme borreliosis. CONCLUSIONS: The prognosis of
      patients treated for Lyme borreliosis in this part of France is excellent.
      Therefore, a complete clinical examination is sufficient as an initial evaluation
      and long-term follow-up is not necessary.

PMID- 12000388
TI  - Systemic lupus erythematosus induced by Epstein-Barr virus infection.
AB  - We report a 22-year-old woman who developed systemic lupus erythematosus (SLE)
      immediately after an Epstein-Barr virus (EBV)-induced mononucleosis infection.
      The link between these two conditions has long been suspected. The close temporal
      relationship, the course of the pathological events and the development of
      immunological changes in this case provide further evidence supporting the
      hypothesis that EBV infection could work as a trigger in some cases of SLE,
      particularly if the patient is genetically susceptible.

PMID- 12000389
TI  - CD30-positive T-cell-rich pseudolymphoma induced by gold acupuncture.
AB  - Cases of pseudolymphoma induced by intradermal gold injection or gold piercing
      have previously been described. Most of these cases showed the histopathological
      finding of B-lymphocyte predominant lymphocytoma cutis. We describe a patient
      with gold acupuncture-induced T-cell-rich pseudolymphoma. Some T cells showed
      positive staining with CD30. The lesions responded to an intralesional injection
      of triamcinolone acetonide.

PMID- 12000390
TI  - Protean manifestations of human papillomavirus type 60 infection on the
      extremities.
AB  - BACKGROUND: Human papillomavirus type 60 (HPV-60) induces a ridged wart or an
      epidermal cyst on the sole of the foot, exhibiting identical pathological
      changes, with a single refractile eosinophilic intracytoplasmic inclusion body in
      infected cells. However, there is no information on the role of HPV-60 in the
      development of cutaneous lesions on other anatomical sites. OBJECTIVES: To
      perform the clinicopathological analysis of various cutaneous lesions of a
      patient in relation to HPV genotype. PATIENT: A 50-year-old male patient
      developed multiple papules, plaques and nodules on his hand, arm and legs.
      RESULTS: Clinicopathologically, the lesions were classified into three
      categories. A common wart on the finger showed papillomatosis and acanthosis
      characterized by numerous keratohyalin granules. Plane warts on the arm showed
      perinuclear vacuolization of the cells in the upper Malpighian layer. On the
      other hand, a pigmented papillomatous nodule on the finger, and the other lesions
      on the hands and legs exhibited similar histological features with a unique
      cytoplasmic eosinophilic inclusion body. All the three categorized lesions were
      equally positive for HPV capsid antigen by immunohistochemistry. By blot
      hybridization analysis for HPV sequences, it was revealed that a common wart on
      the finger and plane warts on the arm harboured HPV-27 and HPV-3, respectively,
      while all the other lesions harboured HPV-60. The histological localization of
      each viral DNA was confirmed in the corresponding lesions by in situ
      hybridization. CONCLUSIONS: HPV-60 is able to induce papular and nodular lesions
      on the extremities.

PMID- 12000391
TI  - Granulomatous lesions of the homolateral limb after previous mastectomy.
AB  - BACKGROUND: Granulomas may be classified as palisaded, sarcoidal, tuberculoid,
      suppurative and foreign body. In cancer patients they are defined as tumour
      related sarcoid granulomas. Otherwise they are classified as granulomatous
      lesions of unknown significance. It is still unknown why neoplastic diseases are
      sometimes associated with granulomas. OBJECTIVES: To investigate granulomas found
      on the same side as a previous mastectomy. METHODS: We studied four women who had
      previously undergone mastectomy and presented with epithelioid cell granulomas of
      the same side as the previous mastectomy. CONCLUSIONS: The association between
      breast cancer and host granulomatous reaction is uncommon. The cases discussed
      may correspond to cutaneous tumour-related sarcoid granuloma reactions.

PMID- 12000392
TI  - Merkel cell carcinoma in a human immunodeficiency virus-infected patient.
AB  - In the general population, Merkel cell carcinoma (MCC) is a very rare
      neuroendocrine primary skin cancer, known for its high propensity for local
      recurrence and distant metastases. Treatment for this neoplasm is individualized
      on the grounds of clinical staging at presentation, and may include surgical
      excision, radiotherapy and chemotherapy. Several studies suggest that MCC occurs
      more frequently and with a more aggressive course in immunocompromised patients
      such as organ transplant recipients and those infected with human
      immunodeficiency virus (HIV). A case of this cutaneous malignancy, characterized
      by a short-term local recurrence and systemic fatal spread in spite of surgical
      treatment, radiotherapy and chemotherapy, is described in a patient with advanced
      HIV infection.

PMID- 12000393
TI  - Lipomatous mixed tumour of the skin: a histological, immunohistochemical and
      ultrastructural study.
AB  - BACKGROUND: Mixed tumours are composed of an admixture of an
      epithelial/myoepithelial and usually a myxochondroid stromal component.
      Adipocytes are found more rarely, and account for a minor part of the tumour. To
      date, only three cases of mixed tumour/pleomorphic adenoma of the salivary gland
      have been described, showing an extensive adipocyte content of more than 90% of
      the tumour tissue. Owing to this peculiarity, some authors have defined it as
      'lipomatous pleomorphic adenoma'. We are not aware of previously reported similar
      lesions in the skin. OBJECTIVES: We report a case of a tumour that occurred as a
      2 x 2 x 1.5 cm nodule in the scalp of a 65-year-old man. Analogies with salivary
      lipomatous pleomorphic adenoma, as well as histogenesis and differential
      diagnoses are discussed here. METHODS: A histological, immunohistochemical and
      ultrastructural study was performed. RESULTS: The tumour was well-circumscribed
      and showed a substantial mature adipose tissue component intermingled with
      epithelial cells arranged in ducts and branching tubules, embedded in a
      fibromyxoid stroma, which was diagnostic of a chondroid syringoma/mixed tumour.
      Adipocytes strongly expressed S-100 protein and cytokeratin 14. Transitional
      elements from epithelial/myoepithelial cells into adipocytes were observed. They
      coexpressed cytokeratin 14, S-100 protein and vimentin, and showed lipid
      droplets, desmosome-type junctions, cytoplasmic tonofilaments and basal lamina.
      CONCLUSIONS: The tumour differed from lipomas with myxoid stroma and from
      lipoadenomas, which show non-proliferating normal sweat glands admixed with
      adipose tissue. Because of the similarity to lipomatous pleomorphic adenoma/mixed
      tumour of salivary glands, we suggest that it should be called 'lipomatous mixed
      tumour of the skin'.

PMID- 12000394
TI  - Sterile suppurative folliculitis associated with acute myeloblastic leukaemia.
AB  - A 20-year-old woman presented with a 4-month history of follicular papules
      distributed over the trunk and extremities. One month later, routine blood tests
      were abnormal, showing acute myeloblastic leukaemia (M1 in the French-American
      British classification). Skin biopsy demonstrated a dermal infiltrate of a large
      number of neutrophils with occasional eosinophils and histiocytes in the vicinity
      of the hair follicle remnants. Intermingled in the infiltrate were atypical cells
      that were morphologically and immunohistochemically identical to leukaemic
      myeloblasts. Cultures of the papules and special stains of the biopsy specimen
      were negative for bacteria and fungi. The follicular eruption improved promptly
      in response to chemotherapy for the leukaemia. We suggest that this case may
      represent a rare, follicular variant of neutrophilic dermatosis associated with
      myelogenous leukaemia.

PMID- 12000395
TI  - Does Hermansky-Pudlak syndrome predispose to systemic lupus erythematosus?
AB  - We report a Japanese patient with Hermansky-Pudlak syndrome (HPS) who developed
      systemic lupus erythematosus (SLE). This is the second case report of HPS
      complicated with SLE. A 1-bp duplication of adenine at codon 441 was found in the
      HPS gene, namely HPS1, which caused a frameshift. This case serves as evidence
      indicating that a patient with HPS can be predisposed to SLE.

PMID- 12000396
TI  - Isolated amelanotic malignant melanoma of the heart.
AB  - We report a 58-year-old woman presenting with dyspnoea and recurrent pulmonary
      embolism. Echocardiography revealed pericardial effusion and a tumour located in
      the atrioventricular groove. Surgical exploration showed tumorous infiltration of
      the ventricle wall and of parts of the atrium. Curative excision was not possible
      and the operation was discontinued. Histology revealed an amelanotic malignant
      melanoma. No other tumour location was detected by scanning procedures. This case
      represents a very rare manifestation of melanoma exclusively located in the
      atrioventricular groove of the heart leading to recurrent pulmonary embolism. A
      review of the literature on cardiac involvement of melanoma is provided.

PMID- 12000397
TI  - Malignant atrophic papulosis in an infant.
AB  - We report a 7-month-old girl with malignant atrophic papulosis (Degos' disease).
      She also showed spontaneous aggregation of platelets. A good clinical response
      was obtained by treatment with aspirin and dipyridamole.

PMID- 12000398
TI  - Persistent erythematous eyelid swelling due to metastatic lobular carcinoma of
      the breast.

PMID- 12000399
TI  - Haematoma complicating arterial Doppler studies.

PMID- 12000400
TI  - Diffuse Bier white spots revealing cryoglobulinaemia.

PMID- 12000401
TI  - Hair density, hair diameter and the prevalence of female pattern hair loss.

PMID- 12000403
TI  - Subcutaneous sarcoidosis mimicking breast carcinoma.

PMID- 12000404
TI  - Acanthosis nigricans without diabetes during pregnancy.

PMID- 12000405
TI  - Arterial embolization caused by injection of hyaluronic acid (Restylane).

PMID- 12000406
TI  - Epidemic occupational dermatitis caused by Pronematus davisi (Acari: Tydeidae).

PMID- 12000410
TI  - How often must we ask for sensitive care before we get it?

PMID- 12000411
TI  - Breastfeeding duration, costs, and benefits of a support program for low-income
      breastfeeding women.
AB  - BACKGROUND: Breastfeeding can ameliorate some of the complex health issues faced
      by low-income families. Women who breastfeed and their infants have lower health
      care costs compared with those who formula feed. Increasing the duration of
      breastfeeding is recognized as a national priority, particularly for low-income
      women. This community-based randomized clinical trial involving low-income
      mothers compared usual care with an intervention comprising hospital and home
      visits, and telephone support by a community health nurse/peer counselor team for
      6 months after delivery. METHODS: Forty-one women were recruited after delivery
      of a full-term singleton infant and randomly assigned to intervention or usual
      care groups. RESULTS: Women receiving the community health intervention breastfed
      longer than the women receiving usual care. The infants in the intervention group
      had fewer sick visits and reported use of fewer medications than infants in the
      usual care group. The intervention cost ($301/mother) was partially offset by
      cost savings on formula and health care. CONCLUSIONS: Community health nurse and
      peer counselor support can increase breastfeeding duration in low-income women,
      and has the potential to reduce total costs including the cost of support.

PMID- 12000412
TI  - Does maternal smoking have a negative physiological effect on breastfeeding? The
      epidemiological evidence.
AB  - BACKGROUND: Women who smoke are less likely to breastfeed their children than
      nonsmokers. It is thought that nicotine has a negative effect on breastmilk
      supply by suppressing prolactin levels. The aim of this review was to assess the
      epidemiological evidence that maternal smoking has a negative physiological
      effect on breastfeeding. METHODS: The following data sources were searched: The
      Cochrane Library, Medline, CINAHL, Current Contents, Psychinfo, Sociological
      Abstracts and the Lactation Resource Centre (Australian Breastfeeding
      Association) using the key words "smoking" and "breastfeeding" or "infant
      feeding." The Journal of Human Lactation and Birth were hand searched. RESULTS:
      Women who smoke are less likely to intend to breastfeed, less likely to initiate
      breastfeeding, and likely to breastfeed for a shorter duration than nonsmokers.
      Several studies have found a dose-response relationship between the number of
      cigarettes smoked each day and breastfeeding intention, initiation, and duration
      that persists after adjusting for confounding factors. In some population groups
      a high proportion of smokers breastfeed successfully. CONCLUSIONS: The
      association between maternal smoking and lack of breastfeeding is consistent
      across different study designs in a range of countries. Given that women who
      smoke are less likely to intend to breastfeed, however, it cannot be assumed that
      the relationship between smoking and duration of breastfeeding is a physiological
      one. If smoking had a consistent negative physiological effect on lactation, one
      would not expect to see such wide variations in breastfeeding rates among women
      who smoke. Therefore, it is likely that psychosocial factors are largely
      responsible for the lower rates of breastfeeding found in women who smoke
      compared with those who do not.

PMID- 12000413
TI  - Baby friendly hospital practices: cesarean section is a persistent barrier to
      early initiation of breastfeeding.
AB  - BACKGROUND: Documented barriers to the implementation of Step 4 of the Baby
      Friendly Hospital Initiative, which relates to early initiation of breastfeeding,
      have not considered the impact of operative intervention in delivery on
      achievement of the goal. This study was designed to test the hypothesis that
      hospital practices in the immediate postpartum period that are associated with
      operative intervention in delivery can affect first mother-infant contact and
      initiation of breastfeeding. METHODS: In a prospective, longitudinal study, a
      sociodemographically representative sample of 203 primiparous women was
      recruited. Participants were interviewed at 2 days postpartum in metropolitan
      hospitals in Melbourne, Australia, and medical records were inspected. At 8
      months postpartum 81 percent of participants completed a postal questionnaire.
      Three mode-of-delivery groups (spontaneous vaginal delivery, instrumentally
      assisted vaginal delivery and cesarean section) and 4 hospital-of-delivery groups
      (including one accredited Baby Friendly Hospital) were compared. RESULTS: Two way
      ANOVA revealed that women who had a cesarean section experienced a significant
      delay in initiating breastfeeding compared with women giving birth vaginally,
      with or without instrumental assistance (p < 0.001). Significant differences in
      this aspect of care were also observed among hospitals, with the Baby-Friendly
      hospital performing significantly better than the other three hospitals (p <
      0.001). An effect due to mode of delivery alone was demonstrated that could not
      be abolished by differences in hospital practices (p = 0.231). Nevertheless,
      shorter elapsed time between birth and initiation of breastfeeding was not
      significantly associated with continuation of breastfeeding at 8 months
      postpartum (p = 0.642). CONCLUSIONS: The findings confirmed that cesarean section
      was a significant barrier to the implementation of Baby Friendly Hospital
      Initiative Step 4 and that hospital practices were amenable to changes that
      enabled its implementation regardless of the mode of delivery.

PMID- 12000414
TI  - Hospital variation in episiotomy use and the risk of perineal trauma during
      childbirth.
AB  - BACKGROUND: Episiotomies are the most frequently performed surgical procedure
      among United States women, but there are no published epidemiological studies of
      the extent of variation in episiotomy use among different obstetrical providers,
      or the outcomes associated with different levels of use. The objective of this
      study was to assess the extent of hospital variation in the use of episiotomy and
      the relationship between hospital episiotomy use and the incidence and risk of
      perineal trauma among women residing in a large urban area in the United States.
      METHODS: Linked birth certificate and hospital discharge data pertaining to
      births to nulliparous women without prolonged labor or obstructed deliveries, and
      with infants weighing between 2500 and 4000 g, were analyzed for 18 major
      maternity hospitals. The relationship between episiotomy use and perineal trauma
      at the hospital level was examined using regression analysis. RESULTS: Hospital
      episiotomy rates ranged from approximately 20 to 73 percent. The rate of third or
      fourth degree perineal lacerations varied from a low of 4 percent to a high of
      more than 13 percent among hospitals. Rates of episiotomy were significantly
      correlated with rates of a third or fourth degree perineal laceration (r = 0.70;
      p < 0.01), and with the hospital-specific, adjusted odds ratios for such
      lacerations (r = 0.65; p < 0.01). CONCLUSIONS: Findings from the analysis of
      epidemiological data for this study population were consistent with those from
      clinical studies, indicating that liberal as opposed to restrictive use of
      episiotomy is unwarranted, and probably even harmful. Hospital episiotomy rates
      exceeded 20 percent in all cases, but such rates appear difficult to justify in
      face of the evidence.

PMID- 12000415
TI  - Clearing up meconium: clinical management and research ethics.

PMID- 12000419
TI  - Women in the crossfire: forced repeat cesareans.

PMID- 12000420
TI  - VBAC and the New England Journal of Medicine.

PMID- 12000434
TI  - Asymptomatic prosthetic valve dysfunction: pannus?

PMID- 12000435
TI  - Tissue engineered heart valves: autologous cell seeding on biodegradable polymer
      scaffold.
AB  - We previously reported on the successful creation of tissue-engineered valve
      leaflets and the implantation of these autologous tissue leaflets in the
      pulmonary valve position. Mixed cell populations of endothelial cells and
      fibroblasts were isolated from explanted ovine arteries. Endothelial cells were
      selectively labeled with an acetylated low-density lipoprotein marker and
      separated from fibroblasts using a fluorescent activated cell sorter. A synthetic
      biodegradable scaffold consisting of polyglycolic acid fibers was seeded first
      with fibroblasts then subsequently coated with endothelial cells. Using these
      methods, autologous cell/polymer constructs were implanted in 6 animals. In 2
      additional control animals, a leaflet of polymer was implanted without prior cell
      seeding. In each animal, using cardiopulmonary bypass, the right-posterior
      leaflet of the pulmonary valve was resected completely and replaced with an
      engineered valve leaflet with (n = 6) or without (n = 2) prior cultured cell
      seeding. After 6 h and 1, 6, 7, 9, and 11 weeks, the animals were sacrificed and
      the implanted valve leaflets were examined histologically, biochemically, and
      biomechanically. Animals receiving leaflets made from polymer without cell
      seeding were sacrificed and examined in a similar fashion after 8 weeks. In the
      control animals, the acellular polymer leaflets were degraded completely leaving
      no residual leaflet tissue at 8 weeks. The tissue-engineered valve leaflet
      persisted in each animal in the experimental group; 4-hydroxyproline analysis of
      the constructs showed a progressive increase in collagen content.
      Immunohistochemical staining demonstrated elastin fibers in the matrix and factor
      VIII on the surface of the leaflet. The cell labeling experiments demonstrated
      that the cells on the leaflets had persisted from the in vitro seeding of the
      leaflets. In the tissue-engineered heart valve leaflet, transplanted autologous
      cells generated proper matrix on the polymer scaffold in a physiologic
      environment at a period of 8 weeks after implantation.

PMID- 12000436
TI  - Histological and immunohistological study of cryopreserved aortic valve grafts:
      the possibility of a clinical application for cryopreserved aortic valve
      xenograft.
AB  - The influence of preservation techniques on xenogeneic immune responses was
      examined to investigate the possibility of their clinical use. Mongrel dogs and
      pigs were used as allogeneic and discordant xenogeneic donors of aortic valve
      grafts, respectively. The allografts and xenografts were implanted in the
      abdominal aorta of mongrel dogs after cryopreservation or after fresh
      preservation. Allografts and xenografts were explanted at Days 7 and 42 for
      histological and immunohistochemical examination. In the fresh preserved
      allografts and the fresh preserved xenografts, the media of aortic wall grafts
      were significantly acellular at 7 days. Significant aortic medial destruction and
      neointimal proliferation with significant destruction of the valve leaflets was
      observed at 42 days. However, no differences were found among the preservation
      techniques in the xenogeneic grafts. To alleviate the lack of homografts,
      approaches such as the tissue-engineered graft may become an alternative in
      patients who are acceptable candidates.

PMID- 12000437
TI  - Experimental evaluation and early clinical results of a new low-profile bileaflet
      aortic valve.
AB  - We performed an experimental and clinical evaluation of a new low-profile
      bileaflet aortic valve (Regent, St. Jude Medical Inc., St. Paul, MN, U.S.A.).
      Common valve sizes were experimentally tested for leakage volume, pressure drop,
      and transvalvular hemodynamics using a pulse duplicator. Thirty patients (mean
      age 60 +/- 7 years, predominant valve stenosis n = 25) received the Regent
      prosthesis for initial clinical evaluation. In vitro evaluation revealed
      equivalent leakage volumes, larger performance indices (0.552 versus 0.513), and
      lower pressure drops in comparison to SJM hemodynamic plus valve controls.
      Clinically, 21 mm (n = 9), 23 mm (n = 12), and 25 mm (n = 9) valves were
      implanted with no significant perioperative complications. Echocardiography
      revealed low transvalvular flow velocities (2.2 +/- 0.4 m/s) and low pressure
      gradients (20 +/- 6 mm Hg) postoperatively and at 6 months follow-up. In vitro
      testing and early clinical results are promising; however, long-term performance
      has to be proven.

PMID- 12000438
TI  - Implications for the establishment of accelerated fatigue test protocols for
      prosthetic heart valves.
AB  - The goal of this research is to establish a reliable methodology for accelerated
      fatigue tests of prosthetic heart valves. A polymer valve was the subject, and
      the influence of various drive parameters on durability was investigated in three
      different machines. Valve lifetime was notably shortened by increasing the cyclic
      rate or stroke even though the maximum pressure difference at valve closure was
      maintained at 120 mm Hg. These results demonstrate that adjustment of the maximum
      transvalvular pressure is not sufficient to ensure tests are conducted under the
      same conditions and indicate that measurement of the dynamic load would be more
      efficacious. Moreover, the locations of tears sustained in the accelerated tests
      differed from those encountered in an animal experiment although in both cases
      the locations were entirely consistent with the areas of strain concentration
      revealed by finite element analysis. These findings should be discussed during a
      revision of ISO 5840.

PMID- 12000439
TI  - Minimally invasive cardiac surgery by the port-access method.
AB  - Recently, minimally invasive surgery has come to be an important theory in
      cardiac surgery, the goal of which is shortening of hospital stay, earlier
      recovery of employment, and cosmetics. In this paper, we will describe our
      experience with port-access cardiac surgery conducted under the support of our
      new technology. This study assesses the quality of cardiac surgery performed by
      the port-access method. The author developed a direct endoaortic clamp balloon
      (Yozu balloon). This balloon is a triple-lumen balloon catheter of 3.6 mm in
      outer diameter and 40 cm in full length. The balloon is inserted directly into
      the ascending aorta. Injection of cardioplegic solution and aortic vent can be
      conducted. Also, we introduce a modified Cosgrove flex clamp to apply in small
      incision surgery, aiming at a less invasive procedure. The modified point is that
      the original, united Cosgrove flex clamp can be divided into the handle part
      equipped with a ratchet, and the bellows part equipped with a clamp jaw. By this
      modification, it became possible to apply the Cosgrove flex clamp
      transthoracically; that is, it became possible to conduct aortic clamping safely
      and securely through this small port of 8 mm in diameter. Port-access cardiac
      surgery is one of the developing and promising methods of cardiac operation. In
      view of future technological progress, we can expect the gradual but wide
      popularization of this method.

PMID- 12000440
TI  - Is low-intensity anticoagulant therapy possible with an open pivot valve?:
      analysis of its development.
AB  - In 1976, the authors became the codevelopers of the first successful bileaflet
      heart valve which has become the standard in valvular surgery. However, there
      still remains a significant rate of thromboembolism and thrombosis which can be
      attributed to the inherent design of cavities in the pivot area. These cavities
      contribute to stagnant areas that lead to thrombus formation. The literature
      indicates that this rate is approximately 2% to 2.5% per patient year. To
      maintain these thromboembolism rates, certain levels of warfarin have had to be
      used leading to a significant rate of bleeding complications. We present the
      theory and development of the new generation of heart valves without cavities and
      with an open semisphere pivot area. Results of 912 years of clinical studies of
      almost 50,000 valves, as well as additional features that have been incorporated
      to improve hemodynamics and quality of life for the patient, are discussed. The
      clinical results of the European Community Certification and U.S. Food and Drug
      Administration premarket application (PMA) studies also are given. The
      differences in the pivot area suggest that a reduction in thromboembolism is
      possible at anticoagulant levels as low as 1.5 international normalization ratio
      (INR) resulting in virtually no bleeding complications. Midterm clinical results
      are encouraging, and studies are being conducted presently to eliminate totally
      anticoagulants in certain patients.

PMID- 12000441
TI  - Left ventricular remodeling after pulmonary autograft aortic valve replacement:
      evaluation with color-Doppler echocardiography and magnetic resonance imaging.
AB  - The superior hemodynamic performance of the pulmonary autograft in aortic
      position is expected to reflect complete regression of hypertrophy and improved
      ventricular function. We evaluated and compared early and midterm transthoracic
      color-Doppler echocardiography (TTE) and magnetic resonance imaging (MRI)
      assessment concerning left ventricular (LV) function, LV mass regression, and
      performance of the semilunar valves. A total of 42 consecutive patients, mean age
      36 +/- 6 years (range 15 to 56 years), were studied. TTE and MRI were performed
      preoperatively, at discharge, and at 6 and 12 months postoperatively. Left
      ventricular diameters and function and LV wall thickness and mass were assessed.
      There was no early and one late postoperative death. Maximum and mean LV outflow
      gradients were significantly reduced (p = 0.0001 and p = 0.0001, respectively).
      There was a significant reduction in left ventricular mass to near normal for all
      patients (p = 0.001) seen after 6 months. This was paralleled by significant
      reductions in the interventricular septum and posterior wall thickness, but
      difference was slight during further follow-up. There was a strong correlation
      between the results obtained by TTE and MRI for LV mass and ejection fraction (r
      = 0.86 and 0. 87, respectively). The pulmonary autograft operation gives
      excellent results that are translated into greater, rapid, and near complete
      regression of LV hypertrophy. Magnetic resonance imaging is a sensitive and
      noninvasive methodology that provides reliable visualization and quantification
      of ventricular performance.

PMID- 12000442
TI  - Short-term result of aortic valve replacement with cryopreserved homograft valve
      in the University of Tokyo Tissue Bank.
AB  - The short-term results after aortic root replacement with 11 cryopreserved aortic
      homografts was examined. Since 1998, the University of Tokyo Tissue Bank has
      supplied 11 aortic homograft valves. Nine of the recipients were male, and the
      average age was 51.2 years. Nine out of 11 patients had suffered from a serious
      condition of native or prosthetic valve infectious endocarditis. All of the
      patients underwent aortic root replacement, and the blood type between the
      patient and the homograft was matched in 8 of the patients. Only 1 patient died
      (9.1%) in the short-term due to sepsis. The preoperative degree of aortic valve
      regurgitation in all of the cases was third or fourth while the regurgitation
      disappeared after the operation in all of them. Thinking of the serious condition
      of our cases preoperatively, the 9.1% operative mortality was quite acceptable.
      Long-term follow-up is necessary to estimate the quality of the homografts.

PMID- 12000443
TI  - Intensive imaging assessment for successful minimally invasive cardiac surgery.
AB  - To clarify special imaging assessment that is useful for minimally invasive
      cardiac surgery (MICS), we examined 141 cases of MICS operations with
      ministernotomy or minithoracotomy. In the 141 patients, 62 valve, 42 coronary, 37
      congenital heart, and 2 other procedures were successfully completed without
      conversion to full sternotomy. Preoperative chest x-ray, computed tomography,
      and/or magnetic resonance imaging were necessary for determining the level of
      ministernotomy, especially in aortic valve operations. Transthoracic
      echocardiography was useful for selecting procedures of mitral valve or
      intracardiac repair through the MICS approach. Intraoperative transesophageal
      echocardiography was essential for continuous monitoring of cardiac function,
      intracardiac flow, air bubbles, and so forth. The above results suggest that
      intensive imaging assessment might be very important for successful MICS
      operations with ministernotomy or minithoracotomy and that extensive indications
      for this technique exist for various cardiovascular diseases.

PMID- 12000444
TI  - Thrombolytic therapy with tissue plasminogen activator for the treatment of
      nonstructural malfunction of bileaflet cardiac valve prostheses.
AB  - This study was conducted to determine the effect of thrombolytic therapy with
      tissue plasminogen activator (t-PA) for nonstructural malfunction of bileaflet
      cardiac valve prostheses. Twenty-seven patients with bileaflet prosthetic valve
      malfunction diagnosed by a combination of cineradiography and transthoracic
      echocardiography were treated with the administration of intravenous t-PA. The
      treatment resulted in complete success in 55.6% (15 of 27), partial success in
      22.2% (6 of 27), and no change in 22.2% (6 of 27). In the complete success and
      partial success groups, the condition of the patients in 85.7% (18 of 21) of the
      cases improved within 24 h after the administration of t-PA. Six cases in whom
      thrombolytic therapy was instituted more than 1 month (ranged from 1 to 38
      months, mean 14.7 months) after the diagnosis of prosthetic valve malfunction
      showed significantly less effectiveness of thrombolytic therapy with t-PA. Only
      one patient (3.7%) had a major complication (thromboembolism) after t-PA
      treatment. The results suggest that thrombolytic therapy with t-PA in patients
      with nonstructural malfunction of bileaflet cardiac valve prostheses is effective
      with low incidence of complication when the treatment is instituted early after
      the diagnosis.

PMID- 12000445
TI  - Aortic root replacement using composite valve graft in patients with aortic valve
      disease and aneurysm of the ascending aorta: twenty years' experience of late
      results.
AB  - The purpose of this study was to evaluate the clinical outcome of composite valve
      graft replacement in 193 patients with aortic valve disease and aneurysm of the
      ascending aorta from January 1980 to June 1999. The clinical outcome was compared
      between the patients diagnosed with Marfan syndrome (M group) and those without
      Marfan syndrome (non-M group), between those with aortic dissection (AD group)
      and without dissection (non-AD group), between 2 different techniques for
      coronary artery reattachment (modified Bentall [mB] and modified Piehler [mP]),
      and between the time of operation (1980-1989 and 1990-1999). Long-term outcome of
      this procedure was almost satisfactory with actuarial survival of 71.5 +/- 4.4%
      at 10 years and freedom from reoperation of 76.5 +/- 4.4% at 10 years. Freedom
      from cardiovascular events and freedom from reoperation were significantly lower
      in the M group and AD group than in the non-M and non-AD groups. Also, actuarial
      survival was significantly higher in the latter 10 years compared with the former
      10 years. It was concluded that the improvement of perioperative management and
      proper selection of the technique for coronary artery reattachment could have
      improved the clinical outcome. In patients with Marfan syndrome or aortic
      dissection, there still remains a higher risk of cardiovascular event and future
      reoperation. Extensive aortic reconstruction or staged operation should be
      performed in such patients.

PMID- 12000446
TI  - Long-term results for aortic valve replacement with small aortic annulus.
AB  - We determined whether aortic prosthesis size influences survival and hemodynamic
      function. Eighty-nine patients who underwent small aortic valve replacement were
      followed. The small internal orifice area index (IOAI) group was defined as
      having an internal orifice area/body surface area ratio of < or = 1.3 cm(2)/m(2)
      (n = 34). The control group was defined as having an IOAI >1.3 cm(2)/m(2) (n =
      55). The actuarial survival rate at 10 years was 74.5% in the small IOAI group
      and 75% in the control group (NS). Freedom from valve-related impairment at 10
      years was 87% in the small IOAI group and 85% in the control group (NS).
      Postoperative pressure gradients were higher in the small IOAI group (p < 0.05).
      Left ventricular mass index decreased in both groups (albeit nonsignificantly in
      the small group, but significantly decreased in the control group). The long-term
      results of aortic valve replacement for patients with small aortic annulus were
      satisfactory. However, the postoperative pressure gradient through the prosthesis
      and left ventricular hypertrophy remained at a high level in the small IOAI
      group.

PMID- 12000447
TI  - Long-term results of valve replacement with the CarboMedics prosthetic heart
      valve.
AB  - This study examined the long-term results of the CarboMedics prosthetic heart
      valve. Between July 1990 and May 2000, 256 CarboMedics valve prostheses (120
      single aortic, 62 single mitral, and 34 double aortic/mitral) were implanted into
      216 patients (mean age 57.8 years). The mean follow-up was 57.7 +/- 36 months
      (maximum 133 months) with a total of 1,038.4 patient years. Patient survival,
      including operative deaths, was 85.1% at 10 years. Linearized rates for various
      complications were thromboembolism 0.39% per patient year, bleeding events 0.39%
      per patient year; prosthetic valve endocarditis 0.29% per patient year,
      nonstructural dysfunction 0.87% per patient year, and reoperation 0.39% per
      patient year. There were no valve thrombosis or structural valve failures in this
      series. The probabilities of freedom from thromboembolism and reoperation at 10
      years were 96.3% and 93.1%, respectively. In conclusion, the CarboMedics valve
      can be used satisfactorily with a low incidence of thromboembolism and valve
      thrombosis.

PMID- 12000448
TI  - Aortic valve replacement in the calcified small aortic root by hemitranslocation
      of the valve.
AB  - An alternative technique of aortic valve replacement is described for a small
      aortic root with a severe large calcific degeneration of the supraaortic area at
      the noncoronary sinus. This technique is used when Nicks or Manouguian procedures
      are not applicable.

PMID- 12000449
TI  - Overexpression of Arabidopsis thaliana farnesyl diphosphate synthase (FPS1S) in
      transgenic Arabidopsis induces a cell death/senescence-like response and reduced
      cytokinin levels.
AB  - To investigate the contribution of farnesyl diphosphate synthase (FPS) to the
      overall control of the mevalonic acid pathway in plants, we have generated
      transgenic Arabidopsis thaliana overexpressing the Arabidopsis FPS1S isoform.
      Despite high levels of FPS activity in transgenic plants (8- to 12-fold as
      compared to wild-type plants), the content of sterols and the levels of 3-hydroxy
      3-methylglutaryl-CoA reductase activity in leaves were similar to those in
      control plants. Plants overexpressing FPS1S showed a cell death/senescence-like
      phenotype and grew less vigorously than wild-type plants. The onset and the
      severity of these phenotypes directly correlated with the levels of FPS activity.
      In leaves of plants with increased FPS activity, the expression of the senescence
      activated gene SAG12 was prematurely induced. Transgenic plants grown in the
      presence of either mevalonic acid (MVA) or the cytokinin 2-isopentenyladenine (2
      iP) recovered the wild-type phenotype. Quantification of endogenous cytokinins
      demonstrated that FPS1S overexpression specifically reduces the levels of
      endogenous zeatin-type cytokinins in leaves. Altogether these results support the
      notion that increasing FPS activity without a concomitant increase of MVA
      production leads to a reduction of IPP and DMAPP available for cytokinin
      biosynthesis. The reduced cytokinin levels would be, at least in part,
      responsible for the phenotypic alterations observed in the transgenic plants. The
      finding that wild-type and transgenic plants accumulated similar increased
      amounts of sterols when grown in the presence of exogenous MVA suggests that
      FPS1S is not limiting for sterol biosynthesis.

PMID- 12000450
TI  - Loading of nitrate into the xylem: apoplastic nitrate controls the voltage
      dependence of X-QUAC, the main anion conductance in xylem-parenchyma cells of
      barley roots.
AB  - We report here that NO(3)(-) in the xylem exerts positive feedback on its loading
      into the xylem through a change in the voltage dependence of the Quickly
      Activating Anion Conductance, X-QUAC. Properties of this conductance were
      investigated on xylem-parenchyma protoplasts prepared from roots of Hordeum
      vulgare by applying the patch-clamp technique. Chord conductances were minimal
      around -40 mV and increased with plasma membrane depolarisation as well as with
      hyperpolarisation. Two gates with opposite voltage dependences were postulated.
      When 30 mM Cl- in the bath was replaced by NO(3)(-), a shift in the midpoint
      potential of the depolarisation-activated gate by about -60 mV from 43 to -16 mV
      occurred (K(m) = 3.4 mM). No such effect was seen when chloride was replaced by
      malate. Addition of 10 mM NO(3)(-)to the pipette solution and reduction of [Cl-]
      from 124 to 4 mM (to simulate cytoplasmic concentrations) did not interfere with
      the voltage dependence of X-QUAC activation, nor was it affected by changes in
      external [K+]. If only the NO(3)(-) effect on gating was considered, an increase
      of the NO(3)(-) concentration in the xylem sap to 5 mM would result in an
      enhancement of NO(3)(-) efflux by about 30%. Although the driving force for
      NO(3)(-) efflux would be reduced simultaneously, NO(3)(-) efflux into the xylem
      through X-QUAC would be maintained with high NO(3)(-) concentrations in the xylem
      sap; a situation which occurs for instance during the night.

PMID- 12000451
TI  - Insights into the evolution of self-compatibility in Lycopersicon from a study of
      stylar factors.
AB  - To elucidate the molecular basis of loss of self-incompatibility in Lycopersicon,
      S-RNases and HT-proteins were analysed in seven self-compatible (SC) and three
      self-incompatible (SI) taxa. No or low stylar RNase activity was a common feature
      in most SC taxa examined, in contrast to the uniformly high levels of activity
      found in all SI species. The S-RNase gene is most likely deleted in the four red
      fruited SC taxa (L. esculentum, L. esculentum var. cerasiforme, L.
      pimpinellifolium and L. cheesmanii) because S-RNase genes could not be amplified
      from genomic DNA. S-RNase genes could, however, be amplified from the genomes of
      the three green-fruited SC taxa examined. L. chmielewskii and L. hirsutum f.
      glabratum show a decreased accumulation of transcripts, possibly reflecting
      changes in the 5' flanking regions of the S-RNase genes. The remaining green
      fruited SC species, L. parviflorum, has a functional S-RNase gene in its genome
      that is expressed at high levels in the style, suggesting a genetic factor
      responsible for the low S-RNase activity. Together these results argue for
      several independent mutations in the S-RNase gene over the course of Lycopersicon
      diversification, and that loss of S-RNase function is unlikely to the primary
      cause of the loss of self-incompatibility. We also examined the HT-B genes that
      play a role in self-incompatibility. HT-B transcripts were markedly reduced in
      the styles of all the SC taxa examined. A scenario is described where a mutation
      causing reduced transcription of HT-B in an ancestral SI species was central to
      the loss of self-incompatibility in Lycopersicon.

PMID- 12000452
TI  - Ribozyme termination of RNA transcripts down-regulate seed fatty acid genes in
      transgenic soybean.
AB  - We investigated whether termination of transcripts with a self-cleaving ribozyme
      can enhance nuclear retention and serve as a tool to decrease specific plant gene
      expression. Nuclear retention was first monitored in tobacco using the beta
      glucuronidase gene terminated with either the 35S CaMV 3' untranslated sequence
      (UTR) or a cis-acting ribozyme. Northern blot analysis of nuclear RNA and total
      RNA, and in situ hybridizations showed that the ribozyme-terminated transcripts
      were preferentially retained in the nucleus of transgenic tobacco. Ribozyme
      terminated transcripts were subsequently tested as a gene down-regulation
      strategy in soybean. The embryo-specific Delta-12 fatty acid desaturase FAD2-1
      gene was targeted because its down-regulation elevates oleic acid content of seed
      storage lipids. Both ribozyme-terminated antisense and standard antisense
      constructs were capable of gene down-regulation, producing over 57% oleic acid
      compared with less than 18% in wild-type seed. Ribozyme termination cassettes
      were also constructed to evaluate sense transcripts for single gene down
      regulation and the simultaneous down-regulation of two embryo-specific genes in
      soybean using a single promoter. Eight independent soybean transformants were
      screened that harboured standard plus sense or ribozyme terminated FAD2-1
      cassette. Two of the eight ribozyme terminated transformants displayed oleic
      acids levels in the seed storage lipids of over 75%, while none of the standard
      plus sense FAD2-1 lines showed elevated oleic acid phenotypes. The dual
      constructs targeted FAD2-1 and the FatB gene encoding a palmitoyl-thioesterase.
      Five transgenic soybean lines harbouring the dual constructs had oleic acid
      levels, greater than 85%, and saturated fatty acids levels, less than 6%. Thus,
      ribozyme termination of transcripts can be utilized to specifically down-regulate
      endogenous gene expression in soybean.

PMID- 12000453
TI  - Seed-specific overexpression of a potato sucrose transporter increases sucrose
      uptake and growth rates of developing pea cotyledons.
AB  - During the storage phase, cotyledons of developing pea seeds are nourished by
      nutrients released to the seed apoplasm by their maternal seed coats. Sucrose is
      transported into pea cotyledons by sucrose/H+ symport mediated by PsSUT1 and
      possibly other sucrose symporters. PsSUT1 is principally localised to plasma
      membranes of cotyledon epidermal and subepidermal transfer cells abutting the
      seed coat. We tested the hypothesis that endogenous sucrose/H+ symporter(s)
      regulate sucrose import into developing pea cotyledons. This was done by
      supplementing their transport activity with a potato sucrose symporter (StSUT1),
      selectively expressed in cotyledon storage parenchyma cells under control of a
      vicilin promoter. In segregating transgenic lines, enhanced [(14)C]sucrose influx
      into cotyledons above wild-type levels was found to be dependent on StSUT1
      expression. The transgene significantly increased (approximately 2-fold)
      transport activity of cotyledon storage parenchyma tissues where it was
      selectively expressed. In contrast, sucrose influx into whole cotyledons through
      the endogenous epidermal transfer cell pathway was increased by only 23% in
      cotyledons expressing the transgene. A similar response was found for rates of
      biomass gain by intact cotyledons and by excised cotyledons cultured on a sucrose
      medium. These observations demonstrate that transport activities of sucrose
      symporters influence cotyledon growth rates. The attenuated effect of StSUT1
      overexpression on sucrose and dry matter fluxes by whole cotyledons is consistent
      with a large proportion of sucrose being taken up at the cotyledonary surface.
      This indicates that the cellular location of sucrose transporter activity plays a
      key role in determining rates of sucrose import into cotyledons.

PMID- 12000454
TI  - Identification of a hard surface contact-induced gene in Colletotrichum
      gloeosporioides conidia as a sterol glycosyl transferase, a novel fungal
      virulence factor.
AB  - Hard surface contact has been known to be necessary to induce infection structure
      (appressorium) formation in many phytopathogenic fungi. However, the molecular
      basis of this requirement is unknown. We have used a differential display
      approach to clone some of the genes induced in the conidia by hard surface
      contact. We report that one of the genes induced by hard-surface contact of the
      conidia of Colletotrichum gloeosporioides, chip6, encodes a protein with homology
      to sterol glycosyl transferases. chip6 expressed in E. coli catalyses glucosyl
      transfer from UDP-glucose to cholesterol. Disruption of chip6 causes a marked
      decrease in the transferase activity and a drastic reduction in virulence on its
      natural host, avocado fruits, although the mutant is capable of normal growth and
      appressorium formation. The requirement for sterol glycosyl transferase for
      pathogenicity suggests a novel biological function for this transferase.

PMID- 12000455
TI  - OsPNH1 regulates leaf development and maintenance of the shoot apical meristem in
      rice.
AB  - The Arabidopsis PINHEAD/ZWILLE (PNH/ZLL) gene is thought to play an important
      role in the formation of the shoot apical meristem (SAM) and in leaf adaxial cell
      specification. To investigate the molecular mechanisms of rice development, we
      have isolated a rice homologue of PNH/ZLL, called OsPNH1. Around the SAM, OsPNH1
      was strongly expressed in developing leaf primordia, specifically in the
      presumptive vascular domains, developing vascular tissues, a few cell-layers of
      the adaxial region, and future bundle sheath extension cells. In the SAM, only
      weak expression was observed in the central region, whereas strong expression was
      detected in the mid-vein region of leaf founder cells in the peripheral SAM
      domain. We produced transgenic rice plants containing the antisense OsPNH1
      strand. The antisense OsPNH1 plants developed malformed leaves with an altered
      vascular arrangement and abnormal internal structure. These plants also formed an
      aberrant SAM with reduced KNOX gene expression. We examined the subcellular
      localization of the OsPNH1-GFP fusion protein and found that it was localized in
      the cytoplasm. On the basis of these observations, we propose that OsPNH1
      functions not only in SAM maintenance as previously thought, but also in leaf
      formation through vascular development.

PMID- 12000456
TI  - Synchronous Arabidopsis suspension cultures for analysis of cell-cycle gene
      activity.
AB  - Synchronized suspension cultures are powerful tools in plant cell-cycle studies.
      However, few Arabidopsis cell cultures are available, and synchrony extending
      over several sequential phases of the cell cycle has not been reported. Here we
      describe the first useful synchrony in Arabidopsis, achieved by selecting the
      rapidly dividing Arabidopsis cell suspensions MM1 and MM2d. Synchrony may be
      achieved either by removing and re-supplying sucrose to the growth media or by
      applying an aphidicolin block/release. Synchronization with aphidicolin produced
      up to 80% S-phase cells and up to 92% G2 cells, together with clear separation of
      different cell-cycle phases. These synchronization procedures can be used for
      analysis of gene expression and protein activity. We show that representatives of
      three CDK gene classes of Arabidopsis (CDKA, CDKB1 and CDKB2) show differential
      expression timing, and that three CDK inhibitor genes show strikingly different
      expression patterns during cell-cycle re-entry. We propose that ICK2 (KRP2) may
      have a specific role in this process.

PMID- 12000457
TI  - A novel in vitro system for simultaneous import of precursor proteins into
      mitochondria and chloroplasts.
AB  - Most chloroplast and mitochondrial precursor proteins are targeted specifically
      to either chloroplasts or mitochondria. However, there is a group of proteins
      that are dual targeted to both organelles. We have developed a novel in vitro
      system for simultaneous import of precursor proteins into mitochondria and
      chloroplasts (dual import system). The mitochondrial precursor of alternative
      oxidase, AOX was specifically targeted only to mitochondria. The chloroplastic
      precursor of small subunit of pea ribulose bisphosphate carboxylase/oxygenase,
      Rubisco, was mistargeted to pea mitochondria in a single import system, but was
      imported only into chloroplasts in the dual import system. The dual targeted
      glutathione reductase GR precursor was targeted to both mitochondria and
      chloroplasts in both systems. The GR pre-sequence could support import of the
      mature Rubisco protein into mitochondria and chloroplasts in the single import
      system but only into chloroplasts in the dual import system. Although the GR pre
      sequence could support import of the mature portion of the mitochondrial FAd
      subunit of the ATP synthase into mitochondria and chloroplasts, mature AOX
      protein was only imported into mitochondria under the control of the GR pre
      sequence in both systems. These results show that the novel dual import system is
      superior to the single import system as it abolishes mistargeting of chloroplast
      precursors into pea mitochondria observed in a single organelle import system.
      The results clearly show that although the GR pre-sequence has dual targeting
      ability, this ability is dependent on the nature of the mature protein.

PMID- 12000458
TI  - Sensitive and high throughput metabolite assays for inorganic pyrophosphate,
      ADPGlc, nucleotide phosphates, and glycolytic intermediates based on a novel
      enzymic cycling system.
AB  - Metabolite assays are required to characterise how metabolism changes between
      genotypes during development and in response to environmental perturbations. They
      provide a springboard to identify important regulatory sites and investigate the
      underlying mechanisms. Due to their small size, Arabidopsis seeds pose a
      technical challenge for such measurements. A set of assays based on a novel
      enzymic cycling system between glycerol-3-phosphate dehydrogenase and glycerol-3
      phosphate oxidase have been developed and optimised for use with growing
      Arabidopsis seeds. In combination with existing assays they provide a suite of
      high throughput, sensitive assays for the immediate precursors for starch
      (adenine diphosphate glucose) and lipid (acetyl coenzyme A, glycerol-3-phosphate)
      synthesis, as well as pyrophosphate, ATP, ADP and most of the glycolytic
      intermediates. A method is also presented to rapidly quench intact siliques,
      lyophilise them and then manually separate seeds for metabolite analysis. These
      techniques are used to investigate changes in overall seed metabolite levels
      during development and maturation, and in response to a stepwise decrease of the
      external oxygen concentration.

PMID- 12000459
TI  - Determination of the elemental composition of mature wheat grain using a modified
      secondary ion mass spectrometer (SIMS).
AB  - An imaging secondary ion mass spectrometry system has been developed that allows
      the distribution of elements or ions to be superimposed on an image of the plant
      cell or tissue generated by ion-induced secondary electrons. This system has been
      evaluated by analysing the aleurone and sub-aleurone cells of mature wheat grain,
      showing high spatial resolution (100-200 nm) images of O-, PO(2)-, Mg+, Ca+, Na+
      and K+ within the phytate granules of the aleurone, with CN- being diagnostic for
      proteins and C(2)- being diagnostic for starch in the starchy endosperm cells.
      This system should provide improved localization of elements in a range of other
      plant systems.

PMID- 12000460
TI  - Analysis of gene expression in Arabidopsis thaliana by array hybridization with
      genomic DNA fragments aligned along chromosomal regions.
AB  - The availability of the entire genomic sequence of the higher plant Arabidopsis
      thaliana prompted an analysis of chromosomal regions for gene expression with the
      use of high-density DNA array filters spotted with genomic DNA fragments (genomic
      DNA array analysis). One TAC and nine P1 clones, each of which contains a genomic
      DNA insert of approximately 80 kb and was used for sequencing of chromosome 5,
      were arbitrarily selected for analysis. The total size of the genomic regions
      corresponding to these clones is 819 kb. A total of 339 DNA fragments (average
      size, 2.9 kb) that cover contiguously the 10 chromosomal regions was selected and
      spotted onto nylon filters. The filters were then subjected to hybridization with
      (33)P-labelled cDNA molecules that had been synthesized from polyadenylated RNA
      isolated from 3-week-old plants. Quantitative and reproducible measurement of
      hybridization signals allowed analysis of the transcription of all genes in the
      targeted regions that were expressed at a level above the limit of detection. The
      data revealed that the analysed chromosomal regions are rich in active genes, and
      that they also provided a basis for the identification of novel transcripts whose
      sequences are not represented in the expressed sequence tag (EST) database.

PMID- 12000461
TI  - Should lipoprotein(a) be measured in pediatric renal transplant recipients?

PMID- 12000462
TI  - Cholelithiasis in pediatric organ transplantation: detection and management.
AB  - The real incidence and the underlying causes of cholelithiasis in pediatric solid
      organ recipients is probably not exactly known. In addition to well-established
      risk factors for cholelithiasis, children after heart, kidney, or liver
      transplantation may develop gallstones due to drug therapy, sepsis, parenteral
      nutrition, or surgical complications. For pediatric patients, data are very
      limited and heterogeneous. However, the incidence in pediatric heart recipients
      seems to be substantially higher compared with kidney or liver graft recipients.
      In this review article the present data are discussed focusing on incidence,
      detection, and management of cholelithiasis in pediatric organ transplantation.
      In general, surgery is the therapy of choice in symptomatic patients; however,
      the pharmacological profile of ursodeoxycholic acid and the first results on its
      clinical impact are promising. The value of prophylactic therapy with
      ursodeoxycholic acid must be determined in further studies.

PMID- 12000463
TI  - Varicella vaccination in pediatric kidney transplant candidates.
AB  - Existing studies support the use of varicella vaccine in a two-dose regimen in
      patients with renal disease prior to transplantation. Levels of anti-varicella
      zoster virus antibody should be monitored on a regular basis after immunization,
      and where a loss of a previously protective antibody titer occurs, a third
      booster dose should be considered pretransplant. Further data need to be
      collected regarding the use of the vaccine in seronegative patients who have
      already undergone transplantation.

PMID- 12000464
TI  - Living-related pediatric renal transplants: a single-center experience from a
      developing country.
AB  - We retrospectively analyzed the results of 75 living-related pediatric renal
      transplants performed at our center between January 1986 and December 1999. The
      major causes of end-stage renal disease (ESRD) were glomerulonephritis (26%) and
      nephrolithiasis (16%), while the etiology was unknown in 50%. The mean age of the
      recipients was 12 yr (range 6-17 yr) and that of the donors was 39 yr (range 20
      65 yr). The majority (73%) of donors were parents. Eighty five per cent of donors
      were one-haplotype matched and the rest identical. Immunosuppression was based on
      a triple drug regimen. Thirty per cent of recipients were rapid metabolizers of
      cyclosporin A (CsA) (area under the curve [AUC]: < 6,000 ng/mL/h), while 16% were
      slow metabolizers (AUC: > 8,000 ng/mL/h). Forty three (57%) children encountered
      59 rejection episodes, the majority of which (59%) were recorded in the first
      month post-transplant. Seventy-four per cent of the rejection episodes were
      steroid sensitive and the rest, except two, were resolved by therapy with
      antithymocyte globulin (ATG) or orthoclone thymocyte 3 (OKT3). After a mean
      follow-up of 37 months, 17 (22%) grafts had chronic rejection and 76% of these
      recipients had previously experienced acute rejection episodes. The overall
      infection rate was high, necessitating two hospital admissions/patient/year. The
      majority (53%) of the infections were bacterial. Urinary tract infections (UTIs)
      were seen in 17 (23%) recipients. Twelve of these had ESRD as a result of stone
      disease and eight grafts were lost because of UTIs. Eight per cent of recipients
      developed tuberculosis (TB), and extra-pulmonary lesions were seen in 50%.
      Surgical complications were encountered in eight patients. Free medication to all
      recipients and parental support ensured a compliance rate of 93%. Baseline growth
      deficit was seen in children of the two groups studied (the 6-12 yr and 13-17 yr
      age-groups), with Z-scores of - 2.39 and - 2.12, respectively. No growth catch-up
      was observed at 12 and 24 months in either group. Post-donation complications
      were seen most commonly in donors > 50 yr of age and included: proteinuria (> 300
      mg/24 h, four patients), hypertension (three patients), and diabetes (one
      patient). Twenty-four grafts were lost, 54% as a result of immunological and the
      rest as a result of non-immunological causes, and 17 recipients died during the
      follow-up period. Infections were the main cause of patient and graft loss.
      Overall 1- and 5-yr graft and patient survival rates were 88% and 65%, and 90%
      and 75%, respectively.

PMID- 12000465
TI  - Predictors of cytomegalovirus disease among pediatric transplant recipients
      within one year of renal transplantation.
AB  - Cytomegalovirus (CMV) is the most important opportunistic infection in renal
      transplant recipients and is associated with an increased risk of rejection.
      Infection can be acquired post-operatively (from the transplanted organ) or from
      re-activation of latent disease. To identify risk factors for CMV disease in a
      pediatric population within 1 yr of renal transplant, and to generate hypotheses
      for the pathogenesis of CMV disease in this population, a review of all
      recipients from 1992 to 1998 in a children's hospital in Atlanta, Georgia, was
      undertaken. Medical records of 73 transplants performed on 72 patients were
      reviewed: nine (12.7%) of 72 individuals, after 73 procedures developed CMV
      disease. Median time to onset of CMV disease was 52 days post-transplant (range =
      15-95 days). Receipts of mycophenolate mofetil (MMF), demographic factors, and
      use of cadaveric kidneys were not associated with a significantly elevated risk
      of CMV disease. Positive donor CMV serostatus was associated with CMV disease
      (uni-variate relative risk [RR] = 8.52, Fisher's Exact Test [FET] p = 0.010).
      Patients with transplants in October or November had a higher risk of developing
      CMV disease (four of 13; 30.8%) than patients transplanted in other months (five
      of 60, 8.3%); RR = 3.69; p = 0.047, FET). Most transplants of patients who did
      not develop CMV disease were performed in January through August (48/64; 75.0%);
      only 25.0% were performed in September through December. In contrast, six of nine
      (66.7%) transplants in patients who subsequently developed CMV disease were
      performed in September through December (p = 0.018, FET). Donor CMV-positive
      serostatus and transplant in October and November continued to be independently
      associated with an increased risk of CMV disease when controlled for other
      factors. The association of transplant in October and November with CMV disease
      in November-January may be related to an increased risk of seasonal community CMV
      exposure and primary CMV infection during the peak season for CMV circulation,
      with subsequent immune suppression promoting progression to disease.
      Alternatively, co-infection with seasonal pathogens after exposure from an
      infected donor during the period of immune suppression may promote progression
      from CMV infection to CMV disease. Further studies should be undertaken to
      explore these and other hypotheses, which may have implications for determination
      of a need for anti-viral prophylaxis.

PMID- 12000466
TI  - Propagation of activated T lymphocytes from endomyocardial biopsy samples of
      cardiac allografts: influence of the addition of recombinant interleukin-4 to the
      culture environment.
AB  - In vivo, activated T cells can be propagated from endomyocardial biopsy (EMB)
      samples of cardiac allografts in cultures containing recombinant interleukin-2
      (rIL-2). However, T cells are sometimes not propagated in such cultures, even
      when rejection is present, and at other times the yield of lymphocytes is too
      small to allow further studies of these graft-infiltrating cells. The current
      study investigated the effects of the addition of recombinant interleukin-4 (rIL
      4) to the culture environment. Cultures were performed on 532 consecutive EMB
      samples from 120 adult and pediatric heart transplant recipients. Each sample was
      divided into multiple fragments. Half of the fragments were cultured in media
      containing 30 U/mL of rIL-2 and the remaining half were cultured under identical
      conditions but with the addition of 200 U/mL of rIL-4. After 14 days, cell counts
      were performed, the cell phenotypes were assessed by flow cytometry, and donor
      specificity and cytotoxicity were assessed using the primed lymphocyte test (PLT)
      and cell-mediated lympholysis (CML) assay, respectively. Lymphocyte growth
      occurred in 18% of grade 0-1a EMB in the presence of rIL-2 and in 29% of grade 0
      1a EMB in the presence of rIL-2/rIL-4 (p = 0.02). For higher-grade EMB
      (equivalent to grade >or=1b), the proportion of positive cultures (approximately
      39%) was similar in both conditions. For positive cultures, there was a 5-fold
      increase in the number of cells in the rIL-2/4 cultures compared to rIL-2 alone
      (1.6 x 10(6) versus 3.4 x 10(5)). Flow cytometry revealed an increase in the
      proportion of CD8+ cells in the rIL-2/4 cultures (42% versus 23%, p = 0.004).
      Proliferative responses to donor antigens (as assessed by using the PLT) were
      comparable between the two groups, but donor-specific cell-mediated cytotoxicity
      was enhanced on addition of rIL-4. Hence, addition of rIL-4 enhances the
      propagation of donor-specific T cells from heart biopsy samples, especially in
      the presence of minimal rejection. This will provide a greater quantity of
      material for further studies of graft-infiltrating cells.

PMID- 12000467
TI  - Efficacy and pharmacokinetics of tacrolimus oral suspension in pediatric liver
      transplant recipients.
AB  - The use of tacrolimus in small pediatric graft recipients may require the
      availability of a suspension formulation for appropriate dose titration and
      easier administration. The pharmacokinetics (Pk) of an extemporaneously prepared
      oral suspension of tacrolimus (OST) was investigated in 15 pediatric liver
      transplant recipients, and was compared with the corresponding data with
      tacrolimus capsules (TC). Graft and patient survival rates were 100%. Acute
      rejection and steroid-resistant rejection were encountered in 9/15 and 3/15
      patients, respectively. Comparison of Pk data showed a lower oral absorption of
      OST when compared with TC. No significant correlation could be made between the
      Pk parameters and rejection. Despite the lower bioavailability of OST when
      compared with TC, the rejection incidence was similar with both formulations (60%
      vs. 55%, respectively). Accordingly, the use of OST may constitute an alternative
      option for tacrolimus administration in low body weight organ recipients, to
      allow dosage titration in the early post-transplant weeks.

PMID- 12000468
TI  - Lipid profile during rhGH therapy in pediatric renal transplant patients.
AB  - To evaluate the effect of recombinant human growth hormone (rhGH) treatment on
      the lipid profile of pediatric renal transplant patients, we studied nine
      children treated with rhGH for 1 yr and a control group of 12 untreated patients
      matched in terms of age, renal transplant function and post-transplant follow-up.
      The levels of lipoprotein (a [Lp(a)], cholesterol, triglycerides, apolipoprotein
      A (APO A) and apolipoprotein B (APO B), and the APO B/APO A ratio, were
      determined at baseline and after 6 and 12 months of follow-up. RhGH therapy had
      no effect on cholesterol, triglycerides or apolipoproteins. Mean serum Lp(a)
      levels increased from 6.7 +/- 5.7 mg/dL at baseline to 11.8 +/- 10.7 after 6
      months (p = 0.018) and 13.6 +/- 15.1 after 12 months of rhGH treatment (p =
      0.04), but did not change in the control group. Lp(a) is a risk factor for
      cardiovascular morbidity, and increased Lp(a) levels may be a side-effect of rhGH
      treatment in renal transplant patients. Although long-term follow-up of a large
      number of patients is needed to establish the duration and extent of the effects
      of rhGH treatment on Lp(a) levels in transplanted children, serum Lp(a) levels
      should be carefully monitored in those receiving rhGH therapy.

PMID- 12000469
TI  - Biliary stricture in living-related donor liver transplantation: management with
      balloon dilation.
AB  - Biliary stricture is a recipient graft complication, occurring late in the post
      operative period, which appears to occur with increased frequency in living
      related donor liver transplantation (LRD LTx). We reviewed the experience at the
      University of Minnesota in managing a biliary complication of LRD LTx. Since
      January 1997, 13 LRD transplants have been performed using the technique of
      transplantation of the left lateral segments with a small portion of segment IV.
      All patients had hepaticojejunostomies using a Roux-en-Y loop. Of the 11
      surviving patients, eight had evidence of cholangitis (Gram-negative sepsis, two
      patients; ascending cholangitis, three patients; or unexplained fever with
      elevated liver enzymes, three patients) 4-8 months after otherwise successful
      transplantation. Six of the patients underwent percutaneous transhepatic
      cholangiography (PTC) with demonstration of a stenosis at the site of the biliary
      anastomosis. Repeated dilation of the anastomosis led to resolution of the
      stenoses, normalization of liver enzymes, and prevention of further episodes of
      infection. No patient required revision of the hepaticojejunostomy. Computed
      axial tomography evidence of ductal stenosis may be subtle in this group of
      patients, but PTC is diagnostic. We suggest a high index of suspicion of biliary
      stricture in the LRD LTx population. Biliary dilation reduces the risk of life
      threatening sepsis.

PMID- 12000470
TI  - Hepatic osteodystrophy in chronic cholestasis: evidence for a multifactorial
      etiology.
AB  - Children with cholestatic liver disease have been thought to develop hepatic
      osteodystrophy resulting from vitamin D and calcium malabsorption, resulting in
      secondary hyperparathyroidism and osteomalacia or rickets. However, treatment
      with vitamin D has not always proven successful in improving the bone
      disturbance. The aim of our study was to determine the role of vitamin D
      deficiency in the pathogenesis of hepatic osteodystrophy. We studied five
      patients, three female and two male, ages 0.9-19 yr, with biopsy-proven chronic
      cholestatic liver disease and previously low serum levels of vitamin D despite
      oral intake of vitamin D preparations. Patients were admitted to the Clinical
      Research Center for 8 days for sunlight deprivation and ultraviolet light
      substitution and for determinations of serum 25-hyroxyvitamin D(25(OH)) D2 and 
      D3, osteocalcin, and type I collagen telopeptide (ICTP), the last two being
      markers of bone formation and resorption, respectively. Samples were taken on
      admission, at discharge, and 1 month later. Results demonstrated low serum levels
      of osteocalcin and normal circulating levels of ICTP. Admission serum 25(OH)D2
      levels were uniformly low or undetectable and remained so. Admission levels of
      circulating 25(OH)D3 were normal or low and did not rise during ultraviolet light
      therapy or subsequent resumption of oral vitamin D therapy and remained low 1
      month later. These results indicate that in the face of low-normal to low total
      25(OH)D levels, the low osteocalcin and normal ICTP levels suggest that decreased
      bone formation and not increased bone resorption is the main determinant of bone
      loss in a subset of children with chronic cholestatic liver disease.

PMID- 12000471
TI  - G protein beta3 subunit 825T genotype is not associated with differing outcome in
      pediatric renal transplant recipients.
AB  - Recent studies have identified a novel polymorphism (C825T) of the gene encoding
      the beta3 subunit of heterotrimeric G proteins (GNB3), associated with enhanced
      activation of G proteins, which appears to be more common in hypertensive
      patients. The donor GNB3 825TT genotype was associated with reduced kidney
      allograft survival in adults. We examined (in 100 Caucasian pediatric renal
      transplant recipients) whether the GNB3 (C825T) polymorphism was associated with
      disease progression and outcome after renal transplantation. The slope of
      1/creatinine was determined by linear regression analysis of a median of 12
      points before and after renal transplantation, and the population was divided
      into two groups of equal size, before and after transplantation, according to the
      slope. The observed frequencies were 57 for the CC, 33 for the CT, and 10 for the
      TT haplotype. For comparison, 738 consecutive newborn babies with the same ethnic
      background were typed in the same hospital. Allele frequencies were statistically
      not significantly different (chi-square test, p = 0.1327). When dividing the
      pediatric renal transplant recipients into two groups with regard to the slope of
      1/creatinine, both before and after renal transplantation, the observed
      proportions were CC 26, CT 17, and TT 7 in the group with the poorer slope and CC
      31, CT 16, and TT 3 in the group with the better slope before renal
      transplantation (not significant [NS], chi-square test, p = 0.1777). The observed
      proportions after renal transplantation were CC 26, CT 16, and TT 8 in the group
      with the poorer slope and CC 31, CT 15, and TT 4 in the group with the better
      slope, respectively (NS, chi-square test, p = 0.167). Allograft survival was not
      associated with the T allele. In conclusion, in a sizeable number of pediatric
      renal transplant recipients the GNB3 C825T polymorphism was found not to be a
      genetic risk factor for end-stage kidney disease. In addition, kidney graft
      function and survival was also found not to be associated with a recipient GNB3
      C825T polymorphism.

PMID- 12000472
TI  - Single-dose pharmacokinetics and tolerability of everolimus in stable pediatric
      renal transplant patients.
AB  - Everolimus (Certican; RAD), a novel macrolide with potent immunosuppressive and
      anti-proliferative activities, prevents acute rejection in adult recipients of
      renal transplantation. This phase I trial conducted in stable pediatric renal
      transplant patients examined the single-dose pharmacokinetics, safety, and
      tolerability of everolimus in combination with cyclosporin A (CsA; Neoral) and
      corticosteroids, with or without azathioprine. Nineteen pediatric patients were
      enrolled and received a single 1.2 mg/m2 dose of everolimus. Everolimus was safe
      and well tolerated, with a low incidence of adverse events reported and none
      judged to be related to the study medication. Everolimus administration did not
      increase infection rates or produce clinically significant changes in vital signs
      or changes in electrocardiograms. Apparent clearance and volume of distribution
      of everolimus increased with age, weight, and body surface area in a generally
      linear manner across the pediatric demographic ranges. Compared with adults from
      a previous study, apparent clearance (L/h) and distribution volume (L) were lower
      in pediatric patients, whereas the elimination half-life was similar. Single-dose
      everolimus co-administration did not affect the steady-state pharmacokinetics of
      CsA. Based on this information, pediatric patients will need a dose scaled down
      for body size, but can probably maintain the same twice-daily dosing schedule
      used in adults.

PMID- 12000473
TI  - Serum C-reactive protein in pediatric kidney and liver transplant patients.
AB  - The clinical manifestations of different complications after organ
      transplantation (Tx) are often vague, and simple laboratory tests for early
      diagnosis would be valuable. In this work we retrospectively analyzed our data on
      the daily measurements of serum C-reactive protein (CRP) in 132 children after 63
      liver and 83 kidney Txs. A total of 3,886 CRP measurements were performed and 353
      episodes of elevated CRP were recorded. One-third of these were regarded as a
      response to surgery. The CRP level normalized within 5-10 days post-operatively
      in patients who had a favorable outcome, but in patients with a poor outcome CRP
      tended to remain elevated. Half of the CRP elevations were associated with
      complications such as acute rejection, infection or thrombotic events. An
      elevated serum CRP level was found in 68% of the rejection episodes, in 88% of
      the bacterial infections, and in 73% of the viral infections. The most
      significant elevations were associated with bacterial infection. In nine of 11
      vascular complications, an elevation of CRP was also recorded. Serum CRP
      responded to rejection therapy in 86% of the episodes. The initial CRP level did
      not predict steroid-resistant rejection. CRP seemed to be a more sensitive marker
      than fever or white blood cell (WBC) count in all complications. We conclude that
      the daily measurement of serum CRP is a simple and fairly sensitive, but non
      specific, method for detecting rejection and infectious complications after
      pediatric liver and kidney Tx.

PMID- 12000474
TI  - Successful renal transplant outcome after intravenous gamma-globulin treatment of
      a highly sensitized pediatric recipient.
AB  - Approximately 10% of patients on the renal transplant (Tx) cadaver waiting list
      have high (> 20%) panel-reactive antibody (PRA) levels to human leukocyte
      antigens (HLA). Intravenous gamma-globulin (IVIG) has been shown to reduce anti
      HLA cytotoxic antibody levels through an anti-idiotypic antibody-blocking effect.
      We report a successful renal Tx outcome in a 7-yr-old-girl with high PRA levels
      owing to a failed renal Tx who experienced a significant reduction in PRA levels
      (from 96% to 0%) concomitant with IVIG therapy. IVIG was infused weekly (500
      mg/kg/week) for 3 consecutive weeks every 12 weeks. Thirty-four months after
      starting IVIG therapy, the PRA activity dropped to zero and IVIG was stopped.
      Then IVIG therapy was resumed after 8 months due to a rebound in PRA activity to
      52%. Forty-four months after starting IVIG therapy, the patient was cross-matched
      with a cadaver donor who shared three antigens with the first living donor. The
      cross-match was positive with the recipient's sera obtained prior to IVIG therapy
      and negative with the recipient's sera obtained post-IVIG therapy. A successful
      cadaver renal Tx was performed using anti-thymocyte globulin (ATGAM) induction
      therapy and a tacrolimus-based immunosuppression protocol. IVIG was given (1
      g/kg) prior to Tx and at day 4 post-operatively. A single mild acute rejection
      episode occurred 10 days post-transplantation that responded to pulse
      methylprednisolone therapy and an increase in the tacrolimus oral dose. We
      conclude that a prolonged course of IVIG infusions, without immunosuppressive
      medications or plasmapheresis, is likely to have been beneficial in modulating
      the immune response in this highly sensitized recipient. Randomized multicenter
      trials are required to define the role of IVIG in this specific population.

PMID- 12000475
TI  - Orthotopic liver transplantation for acute liver failure secondary to autoimmune
      hepatitis in a child with autoimmune polyglandular syndrome type 1.
AB  - Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal-recessive
      condition characterized by hypoparathyroidism, autoimmune Addison's disease, and
      chronic mucocutaneous candidiasis. Autoimmune hepatitis develops in 10-20% of
      affected patients and has a variable course ranging from asymptomatic chronic
      liver disease to lethal fulminant hepatic failure. Liver transplantation has been
      documented previously in only two patients. We report a 14-yr-old boy with APS-1
      who developed acute liver failure secondary to associated autoimmune hepatitis.
      He did not respond to corticosteroid therapy and was successfully treated with an
      orthotopic liver transplant.

PMID- 12000476
TI  - Genetically modified food and the pediatric allergist.

PMID- 12000478
TI  - Critical evaluation of prognostic factors in childhood asthma.
AB  - Current knowledge of the natural history of asthma is improving through the
      establishment of a more precise definition of asthma linked with information from
      a number of large-scale longitudinal studies. Risk factors for the development of
      childhood asthma are now more clearly understood. They include gender, atopic
      status, genetic and familial factors, respiratory infections, and outdoor and
      indoor pollution (1). In the present review two types of asthma and their
      prognosis will be discussed: (1) Asthma in preschool children and its risk
      factors for evolution towards persistent childhood asthma. (2) Asthma in older
      children and its risk factors for evolution towards adult asthma.

PMID- 12000479
TI  - Evaluation of a parental training program for the management of childhood atopic
      dermatitis.
AB  - Atopic dermatitis (AD) in childhood is a common disease with prevalence rates as
      high as 20%. Its early onset in infancy and its chronic relapsing course puts a
      special burden on families. Supporting parents in dealing with the management of
      AD presents a challenge for physicians. The objective of this study was to
      determine the effect of a structured parental training program on managing AD in
      children. Two-hundred and four families participated in a prospective, randomized
      controlled trial. Children (5 months to 12 years in age) had suffered from
      moderate-to-severe AD for at least 4 months. They were randomly assigned to
      either the intervention group or a waiting, control group who could participate
      in the training program 1 year later. The intervention was an inter-disciplinary,
      structured educational program which covered medical, nutritional, and
      psychological issues in six group sessions of 2 h each. The families were
      assessed at the beginning of the study and 1 year later. Main outcome measures
      were: severity of eczema (SCORAD); treatment habits; treatment costs; quality of
      life; and coping strategies. Significant effects were shown regarding treatment
      behavior, such as regular use of emollients, use of antiseptics and topical
      steroids in the event of exacerbation, and a reduction in the use of
      unconventional therapies. Satisfaction with medical treatment was improved, and
      rumination as an ineffective coping strategy was reduced. Finally, significant
      reduction of treatment costs was achieved. We conclude that structured training
      programs for parents of children with AD is a helpful adjunct to dermatological
      treatment.

PMID- 12000480
TI  - The relationship among markers of allergy, asthma, allergic rhinitis, and eczema
      in Costa Rica.
AB  - The association between allergy markers and asthma and allergic rhinitis is
      stronger in countries with a Western lifestyle than in rural areas of Africa and
      Asia. We examined the relationship among allergy markers, asthma, rhinitis, and
      eczema in a case-control study of 198 schoolchildren, 10-13 years of age, living
      in Costa Rica, a Latin American country. The geometric mean total serum
      immunoglobulin E (IgE) level in subjects with and without asthma was 465.0 and
      143.0 IU/ml, respectively (difference = 322 IU/ml, 95% CI = 141.8-616.1 IU/ml, p
      < 0.001), and that in subjects with and without allergic rhinitis was 442.5 and
      144.3 IU/ml, respectively (difference = 298.2 IU/ml, 95% CI = 125.7-581.0 IU/ml,
      p < 0.001). After adjusting for age, gender, and skin test reactivity to
      allergens, we found a linear relationship between serum total IgE level and the
      log odds ratio (OR) of having asthma. In a multivariate analysis, there was a
      linear relationship between skin test reactivity to allergens and the log OR of
      having allergic rhinitis. The OR of having allergic rhinitis was almost three
      times higher in children who had four positive skin tests than in non-reactors.
      Skin test reactivity to greater than five aeroallergens was an independent
      predictor of eczema in a multivariate analysis (OR = 3.1, 95% CI = 1.1-8.4).
      Although the geometric mean total serum IgE levels of Costa Rican children with
      either asthma or allergic rhinitis are higher than those of children with asthma
      or allergic rhinitis in most industrialized countries, the relationship among
      markers of allergy, asthma, rhinitis, and eczema in Costa Rica is similar to that
      found in countries with a Western lifestyle and different from that found in
      rural areas of Asia and Africa.

PMID- 12000481
TI  - Allergic conditions in 5-8-year-old Maltese schoolchildren: prevalence, severity,
      and associated risk factors [ISAAC].
AB  - Allergic conditions, especially asthma, seem to be increasingly common worldwide.
      The International Study of Asthma and Allergies in Childhood (ISAAC) was the
      first study carried out worldwide using standardized questionnaires in order to
      create a reliable global map of childhood allergy. The Maltese Islands were one
      of the centres that participated in this study and in this article the data
      obtained from 3,506 5-8-year-old children from 24 state schools (78.5% response
      rate), and also data obtained from some added 'local' questions addressed to the
      same children, were analyzed in order to evaluate the problem of allergic
      conditions in Maltese schoolchildren. Of the participants, 19.1% were wheezers
      'ever,' while 8.8% were current wheezers. Of the latter, 15.9% experienced
      nocturnal wheezing at least once a week and 13.3% had a wheezing episode of
      sufficient severity to limit speech. Nasal problems were present in 23.4% of
      these children, and in 20.7% of all respondents these symptoms persisted up to
      the year of answering the questionnaire. Hay fever had been diagnosed in 14.7% of
      all the children. Seven per cent of respondents had a recurrent, itchy rash
      (suggestive of eczema) for at least 6 months of their lives and 5.5.% had it
      currently. The prevalence of wheezing and eczema were slightly lower than the
      global mean, unlike rhinitis which in Malta was commoner than the world average.
      Multiple variables, such as gender, breast-feeding, passive smoking, family
      history of atopy, pets, soft furnishings, and living next to busy roads, were
      factors that affected the prevalence and severity of the allergic conditions
      studied. In conclusion, allergic conditions are very common in Maltese
      schoolchildren and cause great hardship to these same youngsters. The results of
      this study should serve as a stimulus to try to decrease this suffering through
      better management of these conditions, measures to control identified detrimental
      factors (such as passive smoking), and further research on asthma, allergic
      rhinitis and eczema.

PMID- 12000482
TI  - Early life factors related to clinical manifestations of atopic disease but not
      to skin-prick test positivity in young children.
AB  - The relative influence of early life events in the development of IgE-mediated
      allergy is still undetermined. We investigated early life factors in relation to
      skin-prick test positivity (SPT) and clinical manifestations of atopic disease in
      a population-based sample of 201 Italian children (3 months-5 years), after
      considering their interactions with known determinants of allergy. Among them,
      143 children had SPT performed to common allergens. Threatened abortions, general
      anesthesia at delivery, prematurity, birthweight < 2500 g, maternal smoking,
      dampness and gas heating exposure were all significantly related to an increased
      risk of frequent rhinitis in the absence of cold (18%). In utero smoking,
      threatened abortions, fetal health complications, infantile colic, maternal
      smoking in childhood (satisfactorily correlated with maternal expired CO during
      the survey) and respiratory infections were all independent determinants of
      frequent wheezing (23%). Doctor's diagnosis of asthma (3%) was related to in
      utero smoking, being born in spring, infantile colic and respiratory infections.
      A simultaneous exposure to in utero smoking and infantile colic put the infants
      to a fourfold higher risk of frequent wheezing and to a ninefold risk of asthma,
      respectively. Having a pet and washing blankets at < 60 degrees C were inversely
      related to frequent wheezing. Data confirmed also that maternal phenotype
      influences the inheritance of atopic disease. No event, except a low intake of
      fruit (< 3/week), was significantly associated with positive SPT (20%) or eczema.
      Besides allergic sensitization, other events, which occur early in life, seem
      critical to the development of IgE-mediated allergy.

PMID- 12000483
TI  - Association of asthma with extra-respiratory symptoms in schoolchildren: two
      cross-sectional studies 6 years apart.
AB  - Epidemiological information on symptoms affecting extra-respiratory organs and
      apparatuses in asthmatic children is scarce. The aim of this study therefore was
      to evaluate, at a population level, if and what extra-respiratory symptoms are
      associated with asthma. Two questionnaire-based, cross-sectional surveys were
      carried out on 1,262 students (651 males; mean age 9.57 years, age-range 6-14
      years) in 1992 and on 1,210 students (639 males; mean age 9.02 years, age-range 6
      14 years) in 1998, from two elementary and two junior high schools in Rome,
      Italy. Questionnaires included queries about asthma and its risk factors and
      extra-respiratory symptoms (headache, restlessness, sleep disturbances,
      urticaria, itching, and abdominal pain). Of responders, 11.9% (279/2,342) had a
      history of asthma. After adjustment for gender, family history of atopic disease,
      low birth weight, early respiratory problems, and damp house, asthma was
      significantly associated with recurrent abdominal pain (odds ratio [OR] 1.90; 95%
      confidence interval [CI]: 1.04, 3.16), itching (OR 3.15; 95% CI: 1.75, 5.68), and
      urticaria (OR 2.52; 95% CI: 1.02, 6.20). Asthma was reported by 10.2% (201/1,962)
      of children unaffected by this triad, by 20.1% (56/279; OR 2.20) with one of the
      symptoms, and by 31.6% (12/38; OR 4.04) with two or more symptoms. An emerging
      characteristic of pediatric asthma in our setting appears to be its association
      with certain extra-respiratory symptoms (abdominal pain, itching, and urticaria).
      A global, internistic approach to asthmatic children is increasingly required
      both in the clinical setting and in future epidemiological studies.

PMID- 12000484
TI  - How do Thai children and adolescents describe asthma symptoms?
AB  - Prevalence of childhood asthma appears to be increasing worldwide. In Thailand,
      the prevalence of childhood asthma increased from 4.2% to 13% within the past
      decade. The last epidemiologic survey in Thailand utilized the International
      Study of Asthma and Allergies in Childhood (ISAAC) phase I questionnaire
      translated into Thai language. Language in the questionnaire can affect the
      reliability and validity of results of the survey. The purpose of this study is
      to determine common Thai wordings actually used by Thai children and adolescents
      to describe wheeze, chest tightness, shortness of breath and dyspnea. Sixty
      asthmatic Thai children, aged 9.2-18 years with asthmatic attacks less than 1 yr
      prior to the study, and 178 age-matched controls were recruited into the study.
      Asthmatic children spontaneously expressed their terms describing their asthma
      symptoms (in Thai) and then answered a preoutlined questionnaire regarding asthma
      terminology during an interview session after viewing the severe attack scene of
      the International ISAAC video questionnaire. Controls responded only to the
      preoutlined questionnaire after viewing the video scene. Of the 60 asthmatic
      children (38 males and 22 females, mean age 11.9 yr), 75% had their last
      asthmatic attacks within 2 months prior to the study. Wheeze was referred to as "
      and '/wi:d/' in 50% and 33% of patients, respectively, and " in 93.8% among
      controls. Using only the word '/wi:d/' in our previous ISAAC-I survey, as it
      sounded like the English word 'wheeze', it appears that up to 67% of the cases
      could have been missed. Dyspnea was referred to as rapid breathing and feeling
      tired in 78.2% of cases and as rapid and difficult breathing in 76.3% of
      controls. Chest tightness was referred to as chest discomfort in 65.7%. Shortness
      of breath was referred to as not being able to catch a breath, too short a
      breath, not enough breath and feeling suffocated in 88.8%. Local terms for asthma
      symptoms should be established and validated into each language to obtain
      reliable epidemiologic data.

PMID- 12000485
TI  - Mould-specific immunoglobulin G antibodies in students from moisture- and mould
      damaged schools: a 3-year follow-up study.
AB  - Immunoglobulin G (IgG) antibodies to moulds have been used as biomarkers of mould
      exposure, though their role reflecting exposure is not confirmed. The purpose of
      the present study was to evaluate the changes in mould-specific IgG antibodies in
      children during a 3-year follow-up in relation to changes in exposure, and to
      allergic and respiratory morbidity. In 1996, 212 primary school students with
      asthma, wheezing or prolonged cough participated in a clinical study, including
      clinical examination, skin-prick tests to 12 moulds and mould-specific IgG
      determinations to 24 moulds. In 1999, 144 students of the same cohort
      participated in an identical follow-up study; among them, mould-specific IgG was
      measured in 121 students. No association was found between IgG antibodies to
      moulds and exposure to moisture or moulds in schools. Likewise, changes in mould
      specific antibodies were only weakly associated with changes in exposure. Mould
      specific IgG antibodies had no significant association with asthma, wheezing or
      cough episodes. IgG antibodies to moulds seem to be poor markers of exposure
      among children exposed to moisture or moulds at school.

PMID- 12000486
TI  - A similar high level of immunoglobulin A and immunoglobulin G class milk
      antibodies and increment of local lymphoid tissue on the duodenal mucosa in
      subjects with cow's milk allergy and recurrent abdominal pains.
AB  - In previous studies, we have reported endoscopic and histological alterations
      locally on the gastrointestinal (GI) tract associated with a gastrointestinal
      type of cow's milk allergy. In this study, we sought to further characterize
      endoscopic, and immunological findings in these children. We also hypothesized
      that the same type of immune responses might also be found in children with
      unexplained and recurrent abdominal pains. We did a gastroduodenoscopy for
      persistent GI symptoms, examined the mucosal histology of the small intestine and
      measured the antibodies to whole cow's milk and its fractions with an enzyme
      linked immunosorbent assay (ELISA) in a consecutive series of 22 subjects with
      untreated and 14 with treated cow's milk allergy (CMA) and 44 with recurrent
      abdominal pains (RAP). The immunological findings of the study subjects were
      compared with 54 controls. Lymphonodular hyperplasia (LNH) of the duodenum was
      the main endoscopic finding in 11 subjects (50%) with untreated and 5 (36%) with
      treated CMA. It was also found in 6 of 44 subjects with RAP. Compared with the
      controls, the patients with CMA showed significantly higher levels of IgA class
      antibodies to whole milk (p = 0.003) and betaLG (p < 0.0001). Of the IgG class
      antibodies to betaLG (p = 0.032), BSA (p < 0.0001) and alphaCAS (p < 0.0001) were
      significantly higher. The patients with LNH of the duodenal bulb as the main
      endoscopic finding showed significantly higher values of IgG class antibodies to
      betaLG (p = 0.01) and alphaCAS (p = 0.005). Interestingly, the patients examined
      for RAP showed a similar increment in the pattern of whole milk and specific milk
      protein antibodies as the CMA children. In conclusion this study showed that
      gastrointestinal CMA beyond infancy is significantly associated with high levels
      of IgG and IgA class antibodies to milk and its fractions. As high levels of
      these antibodies and LNH of the duodenal bulb were also found in subjects with
      RAP, the study further suggests that gastrointestinal CMA might be one major
      reason for RAP.

PMID- 12000487
TI  - Effect of montelukast on exhaled NO in asthmatic children exposed to relevant
      allergens.
AB  - The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)
      sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids
      can prevent this increase. The aim of this study was to evaluate whether
      montelukast could prevent an increase in FENO levels in allergic asthmatic
      children after a brief period of exposure to relevant allergens. Sixteen children
      were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio,
      Italy) in the Italian Alps, a dust mite-free environment. FENO levels were
      evaluated before (t0) and immediately after (t1) the children were exposed to HDM
      allergens for 2 weeks in their homes at sea level. No significant difference in
      FENO was observed in the fluticasone-treated group of children after 2 weeks at
      sea level. In the group treated with montelukast, an increase in FENO was
      observed between t0 and t1, which failed to reach statistical significance. These
      preliminary data suggest that oral montelukast could be effective in preventing
      the relapse in airway inflammation in allergic asthmatic children who are
      occasionally exposed to relevant allergens for a short period of time.

PMID- 12000488
TI  - Prolidase deficiency with hyperimmunoglobulin E: a case report.
AB  - Prolidase deficiency is a rare, inherited disorder characterized by ulceration of
      the skin, mental retardation, and massive urinary excretion of imidodipeptides.
      Most patients also have recurrent infections, an unusual facial appearance, and
      splenomegaly. We describe a girl presenting with chronic dermatitis, recurrent
      respiratory tract infections since her first months of life, and facial features
      characteristic of prolidase deficiency. The diagnosis of prolidase deficiency was
      made at 4.5 months of age. The immunologic study in this patient showed an
      extreme and progressive increase of total immunoglobulin E (IgE) in serum
      (reaching the value of 77,600 IU/l) and defective chemotactic function of the
      neutrophils. Treatment with a hyper-proteic diet supplemented with ascorbic acid,
      manganese chlorite, and topical proline resulted in reduction of the frequency
      and severity of the infections and significant improvement of the skin lesions.
      The authors discuss the immunologic alterations and the favorable evolution with
      treatment in this patient.

PMID- 12000489
TI  - Large T-cell lymphoma in a 13-year-old girl with hyperimmunoglobulinemia E
      syndrome.
AB  - Large T-cell lymphoma was diagnosed in a 13-year-old girl with
      hyperimmunoglobulinemia E syndrome (HIES). Her past medical history included
      severe dermatitis, recurrent pneumonia, urinary tract infections, mucocutaneous
      herpetic infections, fungal skin infections, and staphylococcal sepsis. The
      diagnosis of HIES, based on the clinical features and a serum IgE level of >20000
      IU/ml, was established when the girl was 6 years old. This is the eighth case of
      lymphoma in a patient with HIES reported in the English-language medical
      literature. HIES has not usually been considered a predisposing factor for
      malignancy, but in view of the rarity of HIES and the young age of the patients,
      this association seems to be more than coincidental. A link between lymphoma and
      Epstein-Barr virus (EBV) infection in patients with HIES has been proposed.
      Serological tests for EBV in our patient were positive 6 years prior to the
      development of the lymphoma; however, examination for EBV DNA in the lymph node
      biopsy failed to detect EBV in the tumor.

PMID- 12000492
TI  - 'Real world' pragmatic clinical trials: what are they and what do they tell us?
AB  - Although the explanatory clinical therapeutic trial remains the foundation for
      assessing drug efficacy and is required for licensing purposes, the overall
      effectiveness of a treatment can be best judged by carefully designed and well
      conducted pragmatic 'real world' randomized trials. Pragmatic trials seek to
      inform prescribers and health care planners on the most effective and cost
      beneficial treatments. Pragmatic trials deserve more attention and should be
      included in evidence based guidelines for the pharmacological management of
      common diseases such as asthma and atopy.

PMID- 12000493
TI  - Thromboxane A2 receptor gene polymorphism is associated with the serum
      concentration of cat-specific immunoglobulin E as well as the development and
      severity of asthma in Chinese children.
AB  - Thromboxane A2 and its receptor (TBXA2R) are involved in the constriction of
      vascular and respiratory smooth muscles. The T924C polymorphism in the TBXA2R
      gene was recently found to be associated with asthma in Japanese adults but not
      in children. Its relationship with atopy or asthma severity in children has not
      been defined. To investigate this further, we first assessed the severity of
      asthma in Chinese children using a standardized questionnaire modified from the
      Disease Severity Score and spirometric evaluation. Then, peripheral blood was
      analyzed for serum total and aeroallergen-specific immunoglobulin E (IgE) levels,
      and TBXA2R T924C genotypes were determined by restriction fragment length
      polymorphism (RFLP) analysis. One-hundred and fifty three asthmatic patients and
      57 control children were recruited, of respective mean ages 9.9 and 11.0 years (p
      = 0.07). The mean logarithmic serum total IgE concentration was 2.57 and 2.09,
      respectively, for the asthmatic group and control group (p < 0.0001). Atopy was
      detected in 132 (86%) asthmatics and 33 (58%) controls. A significant association
      was observed between T924C and the diagnosis of atopic asthma (p = 0.044; odds
      ratio: 1.84). In addition, those asthmatics homozygous for the mutant allele in
      T924C had a lower forced expiratory volume in 1 s (FEV1) and forced vital
      capacity (FVC) (p = 0.032 and 0.002, respectively). Among our asthmatic patients,
      the TBXA2R T924C polymorphism correlated with the concentration of cat-specific
      IgE in serum (p = 0.046). Nonetheless, this gene marker did not show an
      association with the serum total IgE concentration or any clinical indicator of
      asthma severity. In conclusion, our results suggest that the T924C marker in the
      TBXA2R gene is associated, in Chinese children, with an increased susceptibility
      of developing atopic asthma. This marker is also associated with the extent of
      allergic sensitization to cat, as well as with reduced FEV1 and FVC values.

PMID- 12000494
TI  - Bee-venom allergy in children: long-term predictive value of standardized
      challenge tests.
AB  - Venom immunotherapy (VIT) is able to protect insect venom-allergic patients
      against life-threatening sting reactions. Standardized sting challenges can be
      used as a diagnostic tool to check whether VIT is required. No data are available
      on the long-term predictive value of sting challenge tests. The purpose of this
      study was to investigate the long-term predictive value of sequential bee-sting
      challenges with respect to the ability to predict future sting reactions in bee
      venom (BV) allergic children. Between 1988 and 1992, 92 BV-allergic children had
      been challenged with sequential bee stings at intervals of 2-6 weeks to determine
      the necessity of VIT. In 1996, all 92 families were followed-up using
      standardized telephone interviews. Until the follow-up, 61 children (66.3%) had
      experienced at least one natural bee sting. Based on the results of the initial
      challenge tests, 13 of the 61 patients had been started on VIT. Two of these 13
      (15.4%) developed systemic reactions 1 year after VIT of 5 years, of which one
      was mild and one was severe. Among the 48 re-stung patients who were not treated
      with VIT, three children (6.3%) experienced mild systemic reactions, whereas 45
      children reported no more than a local reaction. The long-term predictive value
      of sequential bee-sting challenge tests for systemic reactions in children not
      treated with VIT remained at a level of 93.8% (95% confidence interval: 82.8
      98.7%) even over a period of more than 6 years. Based on this data, we conclude
      that sequential bee-sting challenges are a powerful tool to determine the
      necessity for VIT in BV-allergic children.

PMID- 12000495
TI  - Efficacy and safety of inhaled steroid and cromone treatment in school-age
      children: a randomized pragmatic pilot study.
AB  - In the treatment of asthma, inhaled steroids are more effective than cromolyn,
      whereas the latter offers extreme safety. The aim of the present pilot study was
      to evaluate, contemporarily, efficacy and safety aspects of different asthma
      treatment modalities. In 75 school-age children (mean age 9.5 years; range 5.5
      14.7 years), treatment of asthma was started with budesonide (BUD, n = 30),
      fluticasone propionate (FP, n = 30) or cromones (CROM, n = 15). BUD was used at a
      dose of 800 microg/day during the first 2 months and at 400 microg/day
      thereafter. The respective FP doses were 500 and 200 microg/day. Efficacy of the
      treatment was assessed by measuring forced expiratory volume in 1 second (FEV1)
      and by evaluating the use of bronchodilators. Side-effects of the treatment were
      evaluated by following growth of the children and by performing low-dose
      adrenocorticotropin (ACTH) testing. At 4 months FEV1 had improved by a mean of
      8.2% in the BUD group and by 5.4% in the FP group (p< 0.01 vs. baseline in both
      groups; NS between BUD and FP groups). The use of bronchodilators had decreased
      from five doses/week to one dose/week in the BUD group (p< 0.05), and from three
      doses/week to one dose/week in the FP group (p< 0.01) (NS between the groups). In
      the CROM group, the FEV1 value and the use of bronchodilators did not change. The
      treatment was unsuccessful on the basis of FEV1 decrease and increased
      bronchodilator use in, respectively, 30 and 15% of the BUD-, 20 and 7% of the FP
      , and 50 and 47% of the CROM-treated children. Therefore, to prevent one
      treatment failure in the CROM group, between three and five children would need
      to move to treatment with steroids. The treatment had measurable systemic effects
      on the basis of height standard deviation (SD) score decrease and minor
      adrenocortical suppression in, respectively, 60 and 30% of the BUD-, 27 and 17%
      of the FP-, and 20 and 0% of the CROM-treated children. Therefore, to avoid
      systemic effects in one steroid-treated child, three BUD- and six to 14 FP
      treated children would need to move to treatment with CROM. In conclusion, in
      school-age children asthma should be treated first with inhaled steroids. It is
      probable that the best combination of efficacy and safety can be achieved by
      using low steroid doses.

PMID- 12000496
TI  - Placebo-controlled study of the mite allergen-reducing effect of tannic acid plus
      benzyl benzoate on carpets in homes of children with house dust mite
      sensitization and asthma.
AB  - We studied the effect of a spray containing 1% benzyl benzoate, an acaricide, and
      1% tannic acid ('Lowal'; a protein-denaturing substance), on concentrations of
      major allergens from house dust mite (HDM) species Dermatophagoides pteronyssinus
      and D. farinae (Der p 1 and Der f 1, respectively) in carpets. In a double-blind,
      placebo-controlled study with crossover design, 30 homes of children with HDM
      sensitization and asthma were included. All houses showed > or = 400 ng/g of Der
      p 1 + Der f 1 in carpet dust. The first treatment was performed on day 0 (group 1
      active treatment, n = 15; group 2 placebo treatment, n = 15). After 2 and 8
      weeks, dust samples were collected for quantification of mite allergens. After a
      2-week washout period, the second treatment was performed (group 1 placebo
      treatment; group 2 active treatment). Again, carpet dust was collected after 2
      and 8 weeks. Twenty-two of 30 families completed the trial: 14/15 in group 1 and
      eight of 15 in group 2. On day 0, there was no significant difference in mite
      allergen exposure between group 1 and group 2 (1,498 vs. 2,239 ng/g of Der p 1 +
      Der f 1, respectively). In group 1, the geometric mean for the difference of mite
      allergen concentration comparing day 0 and week 6 was 196 ng/g (95% CI: -7,161
      and 8,401) for the first treatment (active) and 15 ng/g (95% CI: -1,079 and
      1,292) for the second treatment (control). In group 2, the difference was 66 ng/g
      (95% CI: -398 and 1,515) for the first treatment (control) and 609 ng/g (95% CI:
      186 and 9,264) for the second treatment (active). Comparing placebo and active
      treatment in total, there was a significant decrease following placebo treatment
      after 14 days (p = 0.026). After 8 weeks, active treatment was superior to
      placebo treatment (p = 0.049), but the allergen reduction achieved was < 20%
      (median 1,500 ng/g on day 0 vs. 1,250 ng/g after 8 weeks). We conclude that the
      slight mite allergen reduction on carpets achieved by the treatment with 'Lowal'
      is unlikely to achieve worthwhile clinical benefit either in the treatment of
      mite-sensitive patients or in primary or secondary prophylaxis.

PMID- 12000497
TI  - Exhaled nitric oxide in healthy children: variability and a lack of correlation
      with atopy.
AB  - Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme
      nitric oxide synthetase (NOS) and can be easily measured in exhaled air by
      chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines
      and endotoxin, NO is elevated in several chronic inflammatory airway diseases.
      Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway
      inflammation in daily routine, the role of possibly influencing factors such as
      age, time of the day, smoking exposure and intra-individual variability have to
      be clarified. NO concentrations were measured in 107 healthy children aged 4-18
      years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were
      performed and a questionnaire on family history of atopy, personal symptoms of
      atopic disease and smoke exposure was completed. For intra-individual variability
      nitric oxide was measured in six children three times daily on 6 consecutive
      days. Median eNO concentration was 5.7 p.p.b., and increased significantly with
      age but did not vary with gender. No correlation was found between eNO and smoke
      exposure, positive skin-prick test, FEV1, MEF25 and time of the day. There was no
      circadian rhythm found in the six children measured on 6 consecutive days, but
      the eNO showed an intra-individual coefficient of variation of 25.9%. With the
      help of a two-compartment model of the lung the alveolar NO concentration was
      estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the
      airway part of NO steadily increased with age. When comparing eNO values with
      standardized measurement techniques, the age of the children and the large intra
      subject coefficient of variation have to be taken into account, whereas in
      healthy children subject-specific factors such as atopic history, gender and skin
      test reactivity did not affect eNO measurement.

PMID- 12000498
TI  - Altered eosinophil levels as a result of viral infection in asthma exacerbation
      in childhood.
AB  - Respiratory viral infection is known to be a significant cause of asthma
      exacerbation. Eosinophils have been considered to play an important role in the
      pathogenesis of virus-induced asthma exacerbations. To determine how often asthma
      exacerbation is caused by virus infections and to examine the relationship
      between eosinophilia and asthma episode, we investigated 64 children who
      experienced asthma attacks between October 1999 and March 2000. We used rapid
      enzyme immunoassays to detect antigens of respiratory syncytial virus (RSV),
      influenza A virus, and adenovirus in nasopharyngeal secretions (NPS) of these
      children, and enumerated eosinophils in the blood and NPS. We detected RSV in 27%
      and influenza A virus in 17% of the patients. No adenovirus infection or
      RSV/influenza A co-infection was detected. RSV-infected children were younger
      (3.85 +/- 0.83 years old) than influenza A virus-infected patients (5.23 +/- 1.34
      years old). Eighty-two per cent of patients in the RSV group and 36% of patients
      in the influenza A virus group had moderate-to-severe asthma episodes (p < 0.05).
      In RSV-infected children, the eosinophil counts in NPS were higher in the
      'severe' group, and younger patients had a greater number of eosinophils in their
      NPS than older patients (p < 0.05). These trends were not found in influenza A
      virus patients. In conclusion, our results indicate that, compared with influenza
      A virus-induced asthma attacks, RSV infection had a higher probability of being
      associated with asthma exacerbation in infants and younger children and induced
      attacks of greater severity. The increase in the number of eosinophils in the NPS
      of RSV-infected children may be responsible, in part, for these differences.

PMID- 12000499
TI  - Family interaction and a supportive social network as salutogenic factors in
      childhood atopic illness.
AB  - The role of psycho-social factors in the development of allergy was studied
      prospectively in 82 infants with a family history of atopy. The family
      participated in a standardized family test when the children were 18 months old.
      The ability to adjust to demands of the situation ('adaptability'), and the
      balance between emotional closeness and distance ('cohesion'), were assessed from
      videotapes by independent raters. Families rated as functional in both of these
      aspects were classified as 'functional', otherwise as 'dysfunctional'. The social
      network, life events, atopic symptoms (based on postal inquiries regarding
      symptoms answered by the parents, and on physical examinations), psychiatric
      symptoms, and socio-economic circumstances of the families were evaluated when
      the children were 18 months and 3 years of age. The children were classified as
      atopic (asthmatic symptoms or eczema) or as non-atopic. All but two children with
      atopic disease at 3 years of age had atopic disease before 18 months of age,
      while 32 of 60 children with atopic disease at 18 months of age had no problems
      by 3 years of age. An unbalanced family interplay at 18 months was associated
      with a relative risk (RR) of 1.99 for continuing atopic illness at 3 years of age
      (1.18 < RR < 3.37, p = 0.01). There was a weak positive confounding effect for
      smoking (RR reduced by 7%), eczema on three or more localizations (RR reduced by
      4.5%), and the amount of cat allergen in household dust (RR reduced by 3%).
      Recovery from atopic illness between 18 months and 3 years of age was four times
      as probable in families with functional interaction and a good social supportive
      network when children were 18 months of age, than in dysfunctional families with
      a poor social network (74% versus 20% p < 0.01). Children with asthmatic symptoms
      showed more signs of emotional distress than did healthy children (p = 0.02).
      Dysfunctional family interaction patterns were more commonly observed in families
      of children who at 3 years of age still had atopic symptoms, than in children who
      had recovered. The patterns included expression of emotion and reaction to the
      needs of others, alternating between total disinterest and over-involvement (p =
      0.02), lack of support and rejection of offered support (p = 0.01), a greater
      number of individual decisions without regard to the other family members (p =
      0.04), and indistinct 'generational boundaries' (p = 0.04). We conclude that
      psychosocial factors, such as family interaction and a supportive social network,
      play a significant role in the course of atopic illness in early childhood and
      that measures which enhance family interaction and the social network could
      influence the course of the disease favorably.

PMID- 12000500
TI  - Cumulative incidence of asthma and allergy in north-Norwegian schoolchildren in
      1985 and 1995.
AB  - The prevalence of asthma and allergy in children is increasing. In order to
      investigate time trends, follow-up studies conducted several years apart and with
      identical study designs are essential. We compared two identical, cross-sectional
      and questionnaire-based studies of asthma and allergy in north-Norwegian
      schoolchildren (7-13 years of age). The first study was conducted in 1985 (n =
      10,093) and the second in 1995 (n = 8,676). The cumulative incidence was as
      follows: diagnosed asthma, 8.6% in 1995 vs. 5.1% in 1985, relative risk (RR) =
      1.71 (95% CI: 1.53-1.90); allergic rhinoconjunctivitis, 22.1% in 1995 vs. 16.4%
      in 1985, RR = 1.39 (95% CI: 1.31-1.47); and atopic dermatitis, 19.7% in 1995 vs.
      13.2% in 1985, RR = 1.48 (95% CI: 1.39-1.58). The cumulative incidence of
      allergic rhinoconjunctivitis and atopic dermatitis was higher in children of Sami
      ethnicity than Norse ethnicity in the 1985 study. Furthermore, although not
      statistically significant, there was a trend towards a greater increase in the
      cumulative incidence of diagnosed asthma, symptoms of asthma, allergic
      rhinoconjunctivitis, and atopic dermatitis from 1985 to 1995 in children of Sami
      ethnicity than Norse ethnicity. We conclude that there has been a marked increase
      in the cumulative incidence of asthma and allergy prevalence among schoolchildren
      in northern Norway from 1985 to 1995.

PMID- 12000501
TI  - Anaphylactic reaction to lychee in a 12-year-old girl: cross-reactivity to latex?
AB  - There are very few case reports on allergic reactions to lychee in the literature
      - so far only in adults. We report on a 12-year-old girl who developed swelling
      of lips, pruritus, generalized urticaria and dyspnea 30 min after eating a raw
      lychee. A second event occurred after eating a piece of cake covered with a fruit
      cocktail. All other foods were well tolerated. In infancy the girl had suffered
      from atopic dermatitis, which disappeared in childhood; for the previous 2 yr she
      had presented with seasonal allergic rhinoconjunctivitis. Upon oral provocation,
      she developed restlessness, flush, generalized urticaria and inspiratory stridor
      50 min after eating half a lychee. The diagnostic work up showed a clear positive
      skin prick test to raw lychee and specific immunoglobulin E (IgE) in serum to
      latex but not to lychee. In the cellular antigen stimulation test (CAST) carried
      out with lychee extracts in several concentrations, the same positive results
      could be found confirming an allergic reaction. Cross-reactivity of lychee to
      latex was shown by inhibition experiments using the UniCAP 100-system. In
      conclusion, it seems worthwhile considering the rare allergy to lychee in the
      case of unclear food-allergic reactions and lychee should be added to the list of
      foods cross-reacting with latex.

PMID- 12000502
TI  - Severe food-induced vasculitis in two children.
AB  - Food-induced vasculitis seems to be rare and is considered by some as
      controversial. The reported cases in the literature are few and mostly on adult
      patients. Described in this report are two children with severe vasculitis caused
      by specific foods. They were diagnosed at two separate allergy centers that have
      a special interest in food allergies. Case 1 was an 8-year-old girl with a 9
      month history of cutaneous vasculitis with large joints involvement. Case 2 was a
      23-month-old girl with an 8-month history of multiple hospitalizations for
      recurrent acute severe cutaneous and mucous membrane vasculitis with large joints
      involvement. In both patients, skin biopsy showed leucocytoclastic vasculitis. In
      neither of the patients could the symptoms be attributed to drug intake,
      infection, autoimmunity, or other systemic disease. Case 1 had a moderately
      elevated serum total immunoglobulin E (IgE) level and strongly positive skin test
      and radioallergosorbent test (RAST) to cow's milk and hen's egg, both of which
      were proven to be the cause by elimination-challenge tests. Case 2 had a slightly
      elevated serum total IgE level, but negative skin tests to foods, including
      chocolate that was suspected by the mother. Avoidance of chocolate resulted in
      remission, except following accidental ingestion of cocoa-containing products.
      These findings support the few previous reports on food-induced vasculitis, an
      entity that seems rare but may be more common than currently realized.

PMID- 12000503
TI  - Antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'
      trimethoxyphenyl)-2-nitro-ethylene.
AB  - The antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'
      trimethoxyphenyl)-2-nitro-ethylene (TMPN) were examined. TMPN was fungicidal for
      the majority of 132 reference strains and clinical isolates tested, including
      those resistant to fluconazole, ketoconazole, amphotericin B or flucytosine.
      Minimum fungicidal concentration/minimum inhibitory concentration (MFC/MIC)
      ratios were < or = 2 for 96% of Cryptococcus neoformans clinical isolates and 71%
      of Candida albicans clinical isolates. TMPN was fungicidal for a variety of other
      basidiomycetes, endomycetes and hyphomycetes, and its activity was unaffected by
      alterations in media pH. The frequency of occurrence of fungal spontaneous
      mutations to resistance was <10(-6). Kill-curve analyses confirmed the fungicidal
      action of TMPN, and demonstrated that killing was concentration- and time
      dependent. At sub-MIC exposure to TMPN, C. albicans did not exhibit yeast/hyphae
      switching. TMPN was slightly cytotoxic for murine and human cancer cell lines
      (GI50=1-4 microg ml(-1)), and weakly inhibited mammalian tubulin polymerization
      (IC50=0.60 microg ml(-1)).

PMID- 12000504
TI  - Comparative evaluation of Candi Select test and conventional methods for
      identification of Candida albicans in routine clinical isolates.
AB  - The Candi Select test (Sanofi Diagnostics, Pasteur, Marnes-La-Coquette, France)
      is a new yeast-selective medium for the identification of Candida albicans in the
      clinical laboratory. The performance of this test was compared with the
      conventional methods of chlamydospore formation, germ tube formation and
      carbohydrate fermentation. Four hundred and twenty clinical yeast isolates from
      412 fresh clinical specimens, including 283 C. albicans, 59 C. tropicalis, 39
      Trichosporon spp., 19 C. glabrata, 11 Cryptococcus neoformans and 9 other yeasts,
      were evaluated. Colonies of C. albicans produced a blue-green colour on the Candi
      Select media which could be distinguished from the other yeasts with the naked
      eye within 24-48 h. The sensitivity and specificity of the Candi Select test for
      the identification of C. albicans were 99.65% and 97.08%, respectively. The blue
      green colonies of C. albicans were easy to identify and recognize in mixed
      cultures and did not need detailed microscopic examination.

PMID- 12000505
TI  - The role of tumour necrosis factor-alpha (TNF-alpha) and platelet-activating
      factor (PAF) interaction on murine candidosis.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is related to some other factors in
      addition to being the essential cytokine of the sepsis which results from Candida
      infections. In our study, we investigated serum TNF-alpha levels, measured by
      enzyme-linked immunosorbent assay (ELISA), and platelet-activating factor (PAF)
      like activity, measured by high-pressure liquid chromatography (HPLC) of the mice
      infected with Candida species. The PAF antagonist, ginkgolide BN 52021 was used
      to evaluate the possible interaction between TNF-alpha and PAF. The average TNF
      alpha levels were found to be 396, 489, 699 and 803 pg ml(-1) on the 4th, 5th,
      6th and 19th days of Candida albicans infection, respectively (P<0.05). There was
      no statistically significant difference between the serum TNF-alpha levels of the
      groups infected with other Candida species, such as C. kefyr, C. krusei and C.
      tropicalis (P>0.05). Serum TNF-alpha levels were found to be more significantly
      different in mice with C. albicans infection that were injected with PAF
      antagonists on the 6th day (23 pg ml(-1)). It was therefore thought that PAF
      antagonists have an inhibitory effect on TNF-alpha production. No significant
      difference was found between PAF levels in the three groups: healthy control
      mice, C. albicans-infected mice and C. albicans-infected mice given PAF
      antagonists (466 milli-absorbance unit (mAU), 475 mAU and 329 mAU, respectively).
      It was noticed that the positive interaction between PAF and TNF-alpha was not
      important after the first 4 days of the infection had passed.

PMID- 12000506
TI  - Susceptibility testing of Malassezia pachydermatis using the urea broth
      microdilution method.
AB  - The in vitro susceptibility of 24 isolates of Malassezia pachydermatis to four
      antifungal drugs in combination with lysozyme was determined using a urea broth
      microdilution method. The antifungal activities of each drug alone against 24
      isolates of M. pachydermatis were determined as the mean minimal inhibitory
      concentrations (MICs). MICs of bifonazole, itraconazole, amorolfine and
      terbinafine were 3.2 microg ml(-1), 1.6 microg ml(-1), 25 microg ml(-1) and 3.2
      microg ml(-1), respectively. Lysozyme alone inhibited the growth of M.
      pachydermatis in a dose-dependent manner, although the lysozyme was unable to
      kill the cells of M. pachydermatis at the highest concentration of 20 microg ml(
      1). Furthermore, the mean MICs of bifonazole, itraconazole, amorolfine and
      terbinafine in combination with lysozyme were the same as the results for each
      drug alone. Although the activity of antifungal drugs in combination with
      lysozyme is enhanced for other fungi. These results suggested that M.
      pachydermatis might not be affected by the host's natural defences.

PMID- 12000507
TI  - Fungistatic activity of some perfumes against otomycotic pathogens.
AB  - The sporostatic effect of five otomycotic pathogens, i.e. Aspergillus niger, A.
      flavus, Absidia corymbifera, Penicillium nigricans and Candida albicans to nine
      different perfumes was determined on the basis of their spore germination. These
      organisms were isolated from patients suffering from fungal infection of the
      external auditory canal. Volatile vapours emanating from musk, phulwari, jasmine,
      nagchampa and bela caused approximately 100% inhibition in spore germination of
      all the test fungi. Volatiles emanating from chandan, khas and hina showed no
      inhibition for the test pathogens, displaying their resistant character to these
      perfumes.

PMID- 12000508
TI  - Clinical comparison of the efficacy and tolerability of once daily Canesten with
      twice daily Nizoral (clotrimazole 1% cream vs. ketoconazole 2% cream) during a 28
      day topical treatment of interdigital tinea pedis.
AB  - The effects of two topical cream formulations containing clotrimazole 1% and
      ketoconazole 2%, respectively, were clinically compared in a double-blind,
      randomized manner for a 28-day therapy of interdigital tinea pedis in 106 treated
      patients. Ketoconazole was to be used twice daily whereas clotrimazole was
      administered only once daily. The primary response criterion defined as the
      number of patients with cure or improvement after 28 treatment days was
      comparable with 62.0% vs. 64.0% (clotrimazole vs. ketoconazole) for the full
      analysis set of 100 (50 vs. 50) patients. The mycological response revealed a
      negative culture and microscopy in 53.1% vs. 52.1% of the patients after 14, in
      76.0% vs. 79.2% after 28, and in 83.7% vs. 76.9% after 56 days of observation,
      indicating a possibly better long-term efficacy of clotrimazole. The development
      of the overall score of tinea-related signs and symptoms did not show relevant
      differences between the two drugs and continuously decreased from 11+/-5 in both
      groups at baseline to 2+/-2 vs. 2+/-1 at day 56. As to the remission and
      improvement rates of single symptoms, better results were obtained under
      clotrimazole than under ketoconazole particularly for pruritus (97.8 vs. 89.6%)
      and burning/stinging (97.5 vs. 89.4%) which both are perceived as most bothersome
      by the patients. Furthermore, both substances appeared as comparably safe and
      well tolerable (8 vs. 7 adverse events with only 1 vs. 3 drug related). In
      conclusion, a successful therapy of tinea pedis can be achieved with both
      clotrimazole and ketoconazole within 28 days of treatment and once-daily
      clotrimazole is equally effective as twice-daily ketoconazole with favourable
      influences on the most irritating symptoms of the disease. Mycological and
      reliable clinical cure cannot be observed during two weeks after start of
      treatment.

PMID- 12000509
TI  - AFSS: athlete's foot severity score. A proposal and validation.
AB  - We developed a simple scoring system to evaluate the severity of tinea pedis
      (Athlete's foot severity score, AFSS). The AFSS consists of a clinical
      evaluation, using a three-point scale, of erythema and scaling in the plantar and
      interdigital spaces of the feet, and counts of interdigital spaces involved. Each
      foot is evaluated separately. The validity of the AFSS was assessed in 224
      soldiers of the Israel Defense Force using mycological cultures as the main
      outcome measure and subjective assessment of pruritus as the secondary outcome
      measure. Mycological examinations were performed in 106 patients who had clinical
      evidence of tinea pedis. AFSS was significantly associated with culture results
      (P<0.0001), as well as with the presence of pruritus (P=0.002), and pruritus
      scores (P=0.025). We conclude the AFSS is valid for the clinical evaluation of
      tinea pedis severity in military settings. The application of AFSS to civilian
      morbidity should be subjected to further evaluation. AFSS: Schweregrad
      Beurteilung des Athletenfusses. Ein Vorschlag

PMID- 12000510
TI  - Dermatophytes and other fungi associated with skin mycoses in Tripoli, Libya.
AB  - This study sought to determine the prevalence of skin infections and their
      causative agents in the Libyan population. Samples were collected from 2224
      patients attending the Dermatology Clinics of the Tripoli Medical Centre (TMC)
      between August 1997 and December 1999 and were submitted to a mycology laboratory
      for analysis. Diagnosis was confirmed by microscopic examination in 1180 cases
      (53.1%) and the causative agent was isolated and cultured in 1160 cases (52.2%).
      Dermatophytes, Malassezia furfur and Candida albicans were the most common
      etiological agents isolated. Tinea corporis accounted for 45.9% of cases (85% of
      cases occurred in children below 15 years of age). The frequency of the other
      clinical types in descending order was pityriasis versicolor 27.8% (322 cases),
      candidiosis 13.4% (156 cases), tinea pedis 8.1% (94 cases), tinea manuum 2.6% (30
      cases) and tinea barbae 2.2% (26 cases). Trichophyton violaceum was the most
      common etiological agent, responsible for 44% (300 cases) of dermatophyte
      infections. Malassezia furfur was ranked the second most frequent causative agent
      being found in 27.8% of cases, followed by Trichophyton rubrum 13.8% (160 cases)
      and Candida albicans 10% (116 cases). Other species isolated included Microsporum
      canis 8.1% (94 cases), Epidermophyton floccosum 6.6% (76 cases) and Trichophyton
      mentagrophytes 3.1% (36 cases).

PMID- 12000511
TI  - A study of dermatophytoses in Sana'a, Yemen Republic.
AB  - The present study describes the extent and causative agents of dermatophytoses in
      Sana'a, the capital of Yemen Republic. Out of 1100 patients with various skin
      diseases, 16.6% were affected with dermatophytoses. Among them, 70% were male and
      the age group 11-20 years was most susceptible to tinea infections. Tinea
      corporis was the most common disease, followed by tinea capitis. One hundred and
      seventy isolates of dermatophytes related to 9 species were identified.
      Microsporum canis was the most prevalent species, followed by Trichophyton
      violaceum.

PMID- 12000512
TI  - Renewed increase in Candida albicans among yeast isolates from the Gottingen
      university hospital.
AB  - We report on the recurrence of Candida albicans among yeast isolates from our
      university hospital. After a decline in occurrence which coincided with the onset
      of the use of fluconazole, the fraction of C. albicans recovered and at present
      has reached the pre-fluconazole level. No permanent rise of C. glabrata or C.
      krusei has been observed.

PMID- 12000513
TI  - Case Reports. Pulmonary cryptococcosis associated with cryptococcal meningitis in
      non-AIDS patients.
AB  - We report four cases of pulmonary cryptococcosis associated with cryptococcal
      meningitis in non-HIV infected patients. All four patients had no apparent
      symptoms and signs of focal lesions that necessitate evaluation for the pulmonary
      lesion. Two out of four patients had radiologic evidence of pulmonary cavitation
      and mass lesions simultaneously, an uncommon finding in non-AIDS patients.
      Diagnostic and therapeutic problems of pulmonary cryptococcosis associated with
      cryptococcal meningitis are discussed.

PMID- 12000514
TI  - Case report. Nattrassia mangiferae endophthalmitis.
AB  - Nattrassia mangiferae is a plant pathogen that is also known as a cause of skin
      infection in humans. Reports of invasive human infection are extremely rare. A 60
      year-old-immunocompetent patient presented with endophthalmitis one week after
      the left eye was injured by a piece of grass. Cultures of an aqueous tap grew N.
      mangiferae. The patient responded to oral ketoconazole. This suggests that N.
      mangiferae may be an invasive pathogen in plant penetration injuries and that
      ketoconazole may be an alternative treatment, especially in countries with poor
      resources.

PMID- 12000515
TI  - Case report. Candida lusitaniae peritonitis in a patient on continuous ambulatory
      peritoneal dialysis.
AB  - We report a case of Candida lusitania peritonitis in continuous ambulatory
      peritoneal dialysis. Since fluconazole therapy was not successful in this
      patient, the peritoneal catheter was removed and antifungal therapy continued,
      and the patient was then converted to haemodialysis. This treatment protocol was
      successful. We suggest that early peritoneal catheter removal should be
      considered in such cases.

PMID- 12000516
TI  - Case reports. Trichosporon mucoides infection in three premature newborns.
AB  - In the present study Trichosporon mucoides infections in 3 premature newborns are
      reported.

PMID- 12000517
TI  - Case report. Pityriasis versicolor mimicking Pityriasis rotunda.
AB  - Pityriasis versicolor is a common dermatomycosis, occurring throughout the world,
      characterized by irregular, slightly scaly patches, varying in color from
      red/light brown to white. Pityriasis rotunda, on the other hand, is an uncommon
      disease, reported in specific ethnic groups, and characterized by perfectly round
      or oval patches of varying color, with a scaly surface. The histologic pattern is
      that of ichthyosis vulgaris. We report here the case of a male patient, aged 31,
      from Sardinia (Italy), affected by Pityriasis versicolor mimicking Pityriasis
      rotunda. Mycological examination allowed us to formulate the correct diagnosis,
      and ensuing treatment with antifungal drugs was entirely successful. The authors,
      while pointing out the rarity of this case, stress the possibility that
      Pityriasis versicolor mimics Pityriasis rotunda and vice-versa, especially in
      those countries in which the two diseases are endemic. More widespread recourse
      to microscopic examination can help avoid the risk of mistaken diagnosis and
      consequent incorrect treatment.

PMID- 12000518
TI  - Case report. First report on human ringworm caused by Arthroderma benhamiae in
      Japan transmitted from a rabbit.
AB  - Two human cases of tinea corporis due to Arthroderma benhamiae (teleomorph of
      Trichophyton mentagrophytes) were described. They acquired the infection from
      their cross-bred rabbit. The three clinical isolates from a human couple and a
      pet rabbit had been identified as A. benhamiae by chitin synthase 1 (CHS1) gene
      analysis as well as by mating experiments. There was no previous isolate of A.
      benhamiae from humans in Japan, although we had reported the first isolate of A.
      benhamiae from a rabbit in 1998. Therefore, this is the first report on human
      ringworm cases caused by A. benhamiae in Japan. It is anticipated that the human
      and animal cases of A. benhamiae infection could rise in number.

PMID- 12000519
TI  - Case reports. Isolation of two Trichosporon cutaneum strains from urine.
AB  - Two strains of Trichopsoron cutaneum were isolated from the urine of two male
      patients. Antifungal susceptibility and cross-reactivity with Cryptococcus
      antigen latex agglutination text as well as the patients' situation are reported.

PMID- 12000520
TI  - Case report. Rosacea-like Tinea incognito.
AB  - We report a case of dermatophytosis of the face due to Microsporum canis that was
      exacerbated and altered clinically by a long-term application of topical
      corticosteroids. We considered this case a rosacea-like tinea incognito of the
      beard area.

PMID- 12000527
TI  - Isoxsuprine hydrochloride in the horse: a review.
AB  - Isoxsuprine hydrochloride has been suggested for use in horses for treatment of
      navicular syndrome and laminitis. The drug has been shown to be a beta
      adrenoreceptor antagonist with beta-adrenoreceptor agonistic properties, with
      both characteristics contributing to vasodilation and uterine relaxation. In
      addition, the drug is capable of decreasing blood viscosity and platelet
      aggregation. Studies have shown i.v. isoxsuprine to have a plasma half-life of <3
      h with a large apparent volume of distribution. Cardiovascular effects resolve
      rapidly following i.v. administration, but are absent with oral dosing. Oral
      bioavailability is 2.2% with a high first pass effect. Isoxsuprine has an
      apparent affinity for melanin that may contribute to extended renal excretion.
      Clinical trials appear to support the use of isoxsuprine for treatment of
      navicular disease. However, poor bioavailability, lack of cardiovascular effects
      following oral administration, superficial support in clinical trials, and new
      evidence regarding the pathogenesis of navicular syndrome indicate that the use
      of isoxsuprine for treatment of navicular syndrome or laminitis is questionable
      at best.

PMID- 12000528
TI  - Pharmacokinetics of ibafloxacin following intravenous and oral administration to
      healthy Beagle dogs.
AB  - The pharmacokinetics of ibafloxacin, a new veterinary fluoroquinolone
      antimicrobial agent, was studied following intravenous (i.v.) and oral
      administration to healthy dogs. The mean absolute bioavailability of ibafloxacin
      after oral doses of 7.5, 15 and 30 mg/kg ranged from 69 to 81%, indicating that
      ibafloxacin was well absorbed by dogs. Ibafloxacin was also absorbed rapidly
      [time of maximum concentration (t(max)) 1.5 h], reaching a mean maximum
      concentration (C(max)) of 6 microg/mL at 15 mg/kg, well distributed in the body
      [large volume of distribution at steady state (V(ss)) and V(area) of 1.1 L/kg and
      4 L/kg, respectively], and exhibited an elimination half-life of 5.2 h and a low
      total body clearance (8.7 mL/min/kg). Both C(max) and area under the
      concentration-time curve (AUC) showed dose proportionality over the dose range
      tested (7.5-30 mg/kg). The pharmacokinetics of ibafloxacin was similar following
      single and repeated dosage regimens, implying no significant accumulation in
      plasma. Food promoted the absorption of ibafloxacin by increasing C(max) and AUC,
      but did not change t(max). High amounts of the metabolites, mainly 8-hydroxy-
      and, 7-hydroxy-ibafloxacin were excreted in urine and faeces, either unchanged or
      as glucuronide conjugates. Following oral administration of 15 mg ibafloxacin/kg,
      the total recovery of ibafloxacin, its metabolites and conjugates in urine and
      faeces was 61.9-99.9% of the dose within 48 h.

PMID- 12000529
TI  - Pharmacokinetics of azithromycin in foals after i.v. and oral dose and
      disposition into phagocytes.
AB  - The properties of azithromycin suggest that it may be an alternative to
      erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate
      this possibility, the disposition of azithromycin in plasma, polymorphonuclear
      leukocytes (PMN), and alveolar cells was examined after a single administration
      in foals. Azithromycin suspension was administered orally (p.o.) at a dose of 10
      mg/kg to five healthy 2-3-month-old foals. Two weeks later, azithromycin for
      injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to
      the same foals. Plasma samples were collected after p.o. and i.v. administration.
      Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were
      collected after p.o. administration. Azithromycin concentrations were determined
      by reverse-phase high-performance liquid chromatography (HPLC) with coulometric
      electrochemical detection. Azithromycin p.o. absorption was variable with a mean
      systemic availability of 39% (+/-20%). The plasma half-life was 16 and 18.3 h
      after i.v. and p.o. administration, respectively. Azithromycin had a very large
      volume of distribution (V(d)) of 11.6 L/kg [V(d(ss))] and 12.4 L/kg [V(d(area))].
      The large V(d) can be attributed to high tissue and intracellular concentrations,
      exhibited by the high concentration of azithromycin in PMN and alveolar cells.
      The PMN half-life was 49.2 h. Dosage of 10 mg/kg of azithromycin p.o. once daily
      for foals with R. equi pneumonia is recommended for further study.

PMID- 12000530
TI  - Cisapride reverses the anticholinergic effect of disopyramide on the isolated
      guinea-pig urinary bladder.
AB  - The present investigation aims to examine whether the prokinetic agent cisapride
      is able to reverse disopyramide's anticholinergic effect on the isolated guinea
      pig urinary bladder. Acetylcholine, at concentrations ranging from 10(-7) to 10(
      3) M, produced a stimulatory effect on the urinary bladder (pEC(50) value=5.1).
      Disopyramide competitively antagonized the contractile effect of acetylcholine
      with an ID(50)=4.4 x 10(-6) M. Although cisapride by itself had either no
      intrinsic contractile action or a modest effect on the urinary bladder, at
      concentrations ranging from 3 x 10(-7) to 10(-6) M, it significantly reversed the
      above inhibitory effect of disopyramide, and produced a parallel leftward shift
      of the concentration-response curve for acetylcholine in the presence of
      disopyramide. The pEC(50) values for acetylcholine in the presence of 3 x 10(-6)
      M and 10(-5) M disopyramide were 4.7 and 4.2, respectively, while in the presence
      of 10(-5) M disopyramide, after pretreatment with 5 x 10(-7) M cisapride, the
      pEC(50) value for acetylcholine was 4.6. It is concluded that cisapride is
      effective in reversing the anticholinergic activity of disopyramide on the
      isolated guinea-pig urinary bladder, probably by facilitating cholinergic
      neurotransmission.

PMID- 12000531
TI  - Loperamide-induced enhancement of moxidectin availability in cattle.
AB  - Moxidectin (MXD) is a milbemycin endectocide compound active at extremely low
      dosages against a wide variety of nematode and arthropod parasites. Different
      pharmacological approaches are currently being tested to delay the bile-faecal
      elimination and to obtain increased systemic availability for endectocide
      molecules in ruminants. Loperamide (LPM) is an opioid derivative, whose main
      pharmacological action is to abolish intestinal propulsive peristaltic waves. The
      influence of LPM on the pattern of faecal excretion of MXD and on its plasma
      disposition following intravenous (i.v.) and subcutaneous (s.c.) administrations
      to cattle was evaluated in the current work. Parasite-free calves were treated
      with MXD given either alone at 200 microg/kg by i.v. (Experiment 1) and s.c.
      (Experiment 2) administrations or coadministered with LPM subcutaneously injected
      at 0.4 mg/kg. Blood and faecal samples were collected over a period of 20
      (Experiment 1) and 40 (Experiment 2) days post-treatment. The recovered plasma
      and faecal samples were extracted and analysed by high-performance liquid
      chromatography (HPLC) using fluorescence detection. Significantly higher MXD
      plasma concentrations were obtained after the coadministration of MXD + LPM
      compared with treatments with MXD alone by both routes. The higher MXD plasma
      concentration profiles measured after the coadministration with LPM accounted for
      the significantly higher AUC values obtained following the i.v. (> 46%) and s.c.
      (> 38%) treatments. A reduced MXD body clearance was observed in the presence of
      LPM. The appearance of MXD in faeces was significantly delayed after the i.v. and
      s.c. coadministrations of MXD with LPM (T(1/2app)=5.87 and 10.6 h, respectively)
      than that observed after the treatment with MXD alone (T(1/2app)=3.48 and 5.12
      h). A delayed MXD peak concentration in faeces collected from MXD + LPM-treated
      animals compared with those receiving MXD alone, was observed. The delayed
      intestinal transit time caused by LPM and a potential competition between MXD and
      LPM for the P-glycoprotein-mediated bile/intestinal secretion processes, may
      account for the enhanced MXD systemic availability measured in cattle in the
      current work.

PMID- 12000532
TI  - Enzyme and plasma protein induction by multiple oral administrations of
      phenobarbital at a therapeutic dosage regimen in dogs.
AB  - In dogs effects of phenobarbital (PB) on hepatic cytochrome P450 (CYP) activities
      and on concentrations of plasma alpha 1-acid glycoprotein (AGP) were examined.
      Total body clearance (Cl(B)) of antipyrine and plasma AGP concentrations were
      monitored during oral PB treatment at a therapeutic dose for 35 days. Cl(B) of
      antipyrine, which reflects hepatic CYP activities, gradually increased and was
      maintained at about threefold concentrations compared with that before treatment,
      suggesting that PB induced CYP activities at a large extent even in a therapeutic
      dose, necessary for an antiepileptic effect. Plasma AGP concentrations also
      increased significantly (about fourfold). Dogs were killed at the 35th day of the
      PB treatment, and hepatic CYP content and enzyme kinetics of several CYPs were
      determined using liver microsomes. CYP content was about twofold higher than that
      from untreated dogs. The V(max) values for CYP1A-like activity (ethoxyresorufin O
      deethylation), 2B-like activity (ethoxycoumarin O-deethylation), 2C-like activity
      (tolbutamide hydroxylation) and 3A-like activity (midazolam 4-hydroxylation) were
      higher (2-4-fold) than that in untreated dogs. In summary, a therapeutic dose of
      PB for antiepileptic therapy significantly induced hepatic CYPs and plasma AGP in
      dogs. Therefore, during antiepileptic therapy with PB, special attention must be
      paid to the pharmacokinetics of drugs simultaneously administered.

PMID- 12000533
TI  - Disposition kinetics of lactoferrin in milk after intramammary administration.
AB  - Disposition kinetics of lactoferrin (Lf) purified from cheese whey was studied in
      the milk of Finnish Ayrshire cows after intramammary administration of 1 g of Lf
      into one udder quarter. Intramammary administration of 1 g of Lf increased Lf
      concentration in milk for several hours. Mean elimination half-life of Lf was 2.2
      h and a mean maximum concentration of 6.3 g/L was reached between 1 and 4 h.
      After 8 h of administration, Lf concentrations in milk decreased to almost the
      same level as before the infusion. Forty-eight hours postinfusion, the mean Lf
      concentration was again higher than in the milk samples taken before the infusion
      of Lf, being on average 1.5 g/L. Lactoferrin caused some local tissue irritation
      in the udder quarter. Severity of the irritation reactions varied between cows.
      The udder quarters of primiparous cows reacted faster than those of multiparous
      cows, but irritation reactions decreased more rapidly in the older cows than in
      primiparous cows. The cows had no general signs such as fever or anorexia. The
      somatic cell count returned to baseline level 4 days after the administration.

PMID- 12000534
TI  - Study of the plasma pharmacokinetics and faecal excretion of the prodrug
      olsalazine and its metabolites after oral administration to horses.
AB  - Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory
      bowel disease in human medicine as an alternative to sulphasalazine over the past
      20 years. Bacteria in the colon split this prodrug into two molecules of the
      locally effective 5-aminosalicylic acid (5-ASA). Considering the potential
      therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after
      single oral administration to six horses at a dosage of 30 mg/kg was
      investigated. Plasma concentrations of OLZ, 5-ASA, and its main metabolite N
      acetyl-5-aminosalicylic acid (Ac-5-ASA) were analysed by high-performance liquid
      chromatography methods. Evaluation of the plasma pharmacokinetics revealed a
      rapid, but low extent of absorption of OLZ (peak concentrations around 1
      microg/mL at 0.5-1.5 h), and a delayed minimal absorption of 5-ASA
      (concentrations < 0.2 microg/mL, at 11-35 h), which is immediately metabolized to
      Ac-5-ASA. As indicators of the local availability in the colon, high faecal water
      concentrations of 5-ASA and Ac-5-ASA (mean C(max) about 300 and 130 microg/mL,
      respectively), but only traces of OLZ were found in faeces excreted 18-50 h after
      dosing. Of the administered OLZ dose 26% could be recovered from faeces, almost
      completely as 5-ASA and Ac-5-ASA. Routine clinical examination of the horses and
      assay of standard haematological and serum chemistry parameters before and after
      OLZ administration confirmed that a single dosage of 30 mg/kg was well tolerated.
      To estimate the systemic availability of 5-ASA liberated from OLZ, 5-ASA was
      administered i.v. at a dosage of 1.5 mg/kg to four horses and plasma
      concentrations of 5-ASA and Ac-5-ASA were determined. The pharmacokinetic
      evaluation showed a very low bioavailability of 2.4% for 5-ASA, released from
      orally administered OLZ. Furthermore, in an in vitro experiment, the metabolic
      transformation of 5-ASA to Ac-5-ASA mediated by bacteria in the caecal content of
      horses was determined at 38 degrees C for 31 h and compared with the metabolism
      data of the in vivo study. The markedly lower degree of acetylation in vitro
      supports the assumption that biotransformation of 5-ASA in vivo occurs not only
      by colonic bacteria, but also at other sites.

PMID- 12000535
TI  - Effects of carprofen (R and S enantiomers and racemate) on the production of IL
      1, IL-6 and TNF-alpha by equine chondrocytes and synoviocytes.
AB  - Chondrocytes and synoviocytes harvested from the joints of healthy horses were
      maintained in tissue culture. Production of the cytokines interleukin-1 (IL-1),
      interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in response to
      lipopolysaccharide (LPS), and the effects of addition of carprofen (racemate and
      R and S enantiomers) were determined. Lipopolysaccharide failed to stimulate TNF
      alpha activity in both cell types but concentrations of IL-1 and IL-6 were both
      increased in a concentration and time-related manner. Both carprofen enantiomers
      and the racemic mixture attenuated the increase in IL-6 induced by LPS in
      synoviocytes, and S carprofen exerted a similar effect on chondrocytes. Neither
      enantiomer nor the racemate of carprofen suppressed the increase in IL-1 release
      produced by LPS in chondrocytes and synoviocytes. An action of carprofen to
      suppress IL-6 release might contribute to the actions which occur in vivo.

PMID- 12000536
TI  - Efficacy and safety of azamethiphos for the treatment of pseudodactylogyrosis in
      the European eel.

PMID- 12000537
TI  - Comparative pharmacokinetics of ivermectin after its subcutaneous administration
      in healthy sheep and sheep infected with mange.

PMID- 12000538
TI  - Immunolesion of hindbrain catecholaminergic projections to the medial
      hypothalamus attenuates penile reflexive erections and alters hypothalamic
      peptide mRNA.
AB  - The central mechanisms underlying diabetes-associated impotence are currently
      unknown. This study utilized immunolesion techniques to eliminate hindbrain
      catecholaminergic projections to the medial hypothalamus which have been reported
      to be glucoresponsive. The immunolesioned male rats had an attenuated feeding
      response to glucoprivic challenge. Furthermore, these lesioned rats had
      significantly attenuated penile reflexes. Northern blot analyses of hypothalamic
      oxytocin mRNA expression showed a significant increase; however, neuropeptide Y
      mRNA expression did not. These results suggest that hindbrain catecholaminergic
      neurones may alter the expression of hypothalamic neuropeptides that stimulate
      penile erections based upon glucoregulatory signals from the periphery.

PMID- 12000539
TI  - Naturally occurring differences in maternal care are associated with the
      expression of oxytocin and vasopressin (V1a) receptors: gender differences.
AB  - Variations in maternal care have been associated with long-term changes in
      neurochemistry and behaviour in adult rats. Rats receiving high levels of licking
      and grooming as pups are less fearful and more maternal than rats receiving low
      levels of maternal licking and grooming. Central pathways for oxytocin and
      vasopressin have been implicated in the neurobiology of anxiety and social
      behaviours. We assessed whether variations in maternal care were associated with
      differences in oxytocin receptors (OTR) or vasopressin (V1a) receptors in the
      brains of adult offspring. In the central nucleus of the amygdala and bed nucleus
      of the stria terminalis, OTR binding was increased in adult females, but not
      adult males, that had received high levels of maternal licking and grooming as
      pups. Conversely, amygdala V1a receptor binding was increased in males, but not
      females, that had received high levels of maternal licking and grooming. These
      findings suggest that variations in maternal care may influence the expression of
      oxytocin and vasopressin receptors in a gender-specific manner.

PMID- 12000540
TI  - Y1 receptor activation is involved in the effect of exogenous neuropeptide Y on
      pup growth and the early termination of lactational diestrus in the postpartum
      rat.
AB  - The effect of chronic administration of exogenous neuropeptide Y (NPY) and
      specific NPY receptor agonists and antagonists on reproductive function was
      examined in lactating rats. As previously demonstrated in our laboratory, chronic
      (7-day) intracerebroventricular (i.c.v.) NPY infusion (6 microg/day) from days 8
      15 postpartum (pp) caused a significant decrease in milk production and an early
      termination of lactational diestrus. Similar application of the mixed Y1/Y4/Y5
      receptor agonist (Leu31, Pro34) NPY (at 3, 6 and 9 microg/day) reproduced the
      effect of chronic NPY infusion on milk production in a dose-independent manner.
      Consistent with this effect, the potent Y1 antagonist/Y4 agonist, 1229U91, given
      concomitantly with NPY eliminated the decline in milk production. The Y2 receptor
      agonist, NPY13-36, had no effect on milk production at any of the doses used.
      Length of lactational diestrus was reduced following administration of the Y2
      agonist at 18 microg/day but not at 9 microg or 27 microg/day whereas (Leu31,
      Pro34) NPY infusion had no effect on this parameter at any of the doses used.
      However, the group that was treated with NPY plus 1229U91 exhibited the usual
      length of lactational diestrus, indicating that there is at least some Y1
      involvement in the effects of NPY on lactational infertility. To test the
      possibility that the effects of NPY infusion are mediated through changes in
      circulating prolactin and progesterone, plasma concentrations of these hormones
      were measured on day 15 pp in NPY-, (Leu31, Pro34) NPY- and vehicle-treated
      females. NPY-infused females had lower plasma prolactin concentrations than
      vehicle-infused dams but progesterone concentrations were similar across groups.
      Overall, these data indicate that chronic exogenous NPY-infusion in lactating
      females disrupts milk production and shortens lactational diestrus, most likely
      through reducing prolactin secretion, and that this effect is mediated via Y1
      receptor activity.

PMID- 12000541
TI  - Mitogen-activated protein kinase mediates epidermal growth factor-induced
      morphogenesis in pituitary GH3 cells.
AB  - Epidermal growth factor (EGF) causes pituitary GH3 cells to change from their
      normal predominantly rounded morphology to much more elongated cells with
      extensive filopodia, and this effect is accompanied by a parallel increase in
      cell volume. In view of this, and because EGF receptor expression is increased in
      some pituitary tumours, we examined the mechanism of this EGF-induced
      morphological effect as it may play a role in tumour invasiveness. The effect of
      treatment of the cells with EGF (1 nm, 4 days) was determined visually (expressed
      as percent non round cells) and by measuring the cell volume by Coulter Counter
      analysis. EGF treatment caused the cells to change their morphology with percent
      non round cells increasing from 37% in control cells to 74% in EGF-treated
      cultures; this was accompanied by a parallel increase in cell volume. Treatment
      of the cells with EGF in the presence of the MEK1 inhibitor (PD98059) completely
      blocked the EGF-induced morphological changes, showing that activation of the
      mitogen-activated protein kinase (MAPK) pathway is necessary to mediate this
      effect. Transfection of the cells with a constitutively activated mutant of MEK1
      produced a similar morphological change to that produced by EGF treatment, with
      the proportion of non round cells increasing to 62% with a parallel increase in
      cell volume compared to cells transfected with the empty vector, demonstrating
      that direct activation of MAPK pathway is sufficient to mediate the observed
      morphological effects. The effects produced by activated MEK1 transfection could
      be blocked by PD98059. EGF had opposing effects on prolactin and growth hormone
      (GH) secretion by the cells, increasing prolactin release and inhibiting GH
      release. Transfection of the cells with activated MEK1 produced similar effects
      on hormone release as EGF treatment. In conclusion, the morphological effects of
      EGF on GH3 cells are mediated by activation of the MAPK pathway as blockade of
      this pathway abolished the observed effect, and direct activation of this pathway
      by transfection with an activated mutant of MEK1 was able to duplicate these
      effects. This mechanism may contribute to the growth and possibly local
      invasiveness of some pituitary tumours that express the EGF receptor.

PMID- 12000542
TI  - Photoperiod and androgens act independently to induce spinal nucleus of the
      bulbocavernosus neuromuscular plasticity in the Siberian hamster, Phodopus
      sungorus.
AB  - In the Siberian hamster, Phodopus sungorus, short-day photoperiods induce the
      winter phenotype, which in males includes a decrease in the production of
      androgens and changes in physiology to inhibit reproduction. Motoneurones of the
      spinal nucleus of the bulbocavernosus (SNB) and their target muscles, the
      bulbocavernosus and the levator ani, a neuromuscular system involved in male
      copulation, also display seasonal plasticity in P. sungorus. It is not known
      whether the plasticity seen in the SNB system of gonadally intact hamsters is due
      to the effects of photoperiod per se, or to the photoperiod-induced changes in
      androgen production. To answer this question, we castrated adult male hamsters
      from long days and then implanted them with capsules containing either
      testosterone or blanks. Half of the hamsters from each hormone condition were
      moved into short photoperiod (8 : 16 h light/dark cycle) while the rest were
      maintained under long-day conditions (15 : 9 h light/dark cycle). After 15 weeks,
      many measures of the SNB system, such as somata size and weight of target
      muscles, responded only to androgen, not to photoperiod. However, there were
      effects of photoperiod on the neuromuscular junctions (NMJs) that were
      independent of androgen status. For example, the number of synaptic zones per NMJ
      and the area of the NMJs were significantly increased by short days and/or
      testosterone treatment. The two factors exerted an additive, rather than an
      interactive, effect on these measures. Another striated muscle, the extensor
      digitorum longus, which is present in both sexes and plays no specialized role in
      reproduction, displayed neither an effect of androgen nor of photoperiod on fibre
      size or NMJ structure. These results suggest that, in addition to androgenic
      effects on SNB plasticity, there is also an androgen-independent effect of
      photoperiod on the SNB neuromuscular system.

PMID- 12000543
TI  - Redefining gonadotropin-releasing hormone (GnRH) cell groups in the male Syrian
      hamster: testosterone regulates GnRH mRNA in the tenia tecta.
AB  - Gonadotropin-releasing hormone (GnRH) regulates the production of testosterone
      via the hypothalamic-pituitary-gonadal axis and testosterone, in turn, regulates
      the GnRH system via negative feedback. We compared testosterone regulation of
      GnRH mRNA expression in four anatomically defined GnRH cell groups in juvenile
      and adult male Syrian hamsters, including a rostral population of GnRH cells in
      the tenia tecta. In situ hybridization histochemistry (ISHH) was used to measure
      GnRH mRNA in brains from castrated juveniles and adults treated with 0 mg or 2.5
      mg testosterone pellets for one week. ISHH was performed on coronal sections
      using a 35S-cRNA probe generated from Syrian hamster GnRH cDNA. Testosterone
      treatment resulted in a significant reduction in mean area of GnRH neurones
      covered by silver grains within the tenia tecta, but only a trend toward
      decreased GnRH mRNA in the diagonal band of Broca/organum vasculosum of the
      lamina terminalis (DBB/OVLT), medial septum (MS), and caudal preoptic area
      (cPOA). The effects of testosterone were independent of age. Frequency
      distribution analyses unveiled a significant reduction in the number of heavily
      labelled cells following testosterone treatment within the tenia tecta and MS.
      Simple regression analyses revealed a significant positive correlation between
      plasma luteinizing hormone concentrations and GnRH mRNA only in the tenia tecta.
      These data indicate that, overall, GnRH mRNA is modestly reduced by testosterone,
      and the most robust attenuation of GnRH mRNA occurs within the tenia tecta. This
      is the first report to link mechanisms of steroid negative feedback with tenia
      tecta GnRH neurones, providing a new focus for investigating brain region
      specific steroidal regulation of GnRH synthesis.

PMID- 12000544
TI  - Brain structures mediating the suckling stimulus-induced release of prolactin.
AB  - Suckling-induced prolactin release is a widely studied neuroendocrine reflex,
      comprising a neural afferent and a humoral efferent component. The information on
      the brain structures involved in this reflex is fairly limited. The present
      studies focused on this question. The following hypothalamic interventions were
      made in lactating rats and the dams were tested for the suckling-induced
      prolactin response: (i) unilateral or (ii) bilateral frontal cuts at the level of
      the anterior and posterior hypothalamus; (iii) administration of 5,7
      dihydroxytryptamine or (iv) 6-hydroxydopamine into the hypothalamic
      paraventricular nucleus (PVN) to destroy serotonergic and catecholaminergic
      innervation of the cell group, respectively; (v) lesion of the medial subdivision
      of the PVN; and (vi) horizontal knife cuts below the PVN. Bilateral posterior and
      bilateral or unilateral anterior frontal cuts caused blockade of the suckling
      induced release of prolactin. Likewise, most dams receiving 5,7
      dihydroxytryptamine in the PVN did not respond to the suckling stimulus.
      Immunocytochemistry revealed that, in those rats which did not show a rise in
      plasma prolactin, there were almost no serotonergic fibres and terminals in the
      PVN, while in dams which exhibited a response, numerous serotonergic elements
      were evident. 6-Hydroxydopamine treatment did not cause significant alteration in
      the prolactin response. Lesion of the medial, largely parvocellular subdivision
      of the PVN, or horizontal knife cuts below this cell group, blocked the hormone
      response. The findings demonstrate for the first time that: (i) interruption of
      the connections between the brain stem and the hypothalamus interferes with the
      prolactin response to the suckling stimulus; (ii) serotonergic fibres terminating
      in the hypothalamic PVN are involved in the mediation of the suckling stimulus;
      and (iii) within the PVN, neurones in the medial, largely parvocellular
      subdivision of the cell group take part in the transfer of the neural signal,
      eventually inducing prolactin release.

PMID- 12000545
TI  - Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress.
AB  - Chronic sleep restriction is an increasing problem in many countries and may have
      many, as yet unknown, consequences for health and well being. Studies in both
      humans and rats suggest that sleep deprivation may activate the hypothalamic
      pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems.
      However, few attempts have been made to examine how sleep loss affects the HPA
      axis response to subsequent stressors. Furthermore, most studies applied short
      lasting total sleep deprivation and not restriction of sleep over a longer period
      of time, as often occurs in human society. Using the rat as our model species, we
      investigated: (i) the HPA axis activity during and after sleep deprivation and
      (ii) the effect of sleep loss on the subsequent HPA response to a novel stressor.
      In one experiment, rats were subjected to 48 h of sleep deprivation by placing
      them in slowly rotating wheels. Control rats were placed in nonrotating wheels.
      In a second experiment, rats were subjected to an 8-day sleep restriction
      protocol allowing 4 h of sleep each day. To test the effects of sleep loss on
      subsequent stress reactivity, rats were subjected to a 30-min restraint stress.
      Blood samples were taken at several time points and analysed for
      adrenocorticotropic hormone (ACTH) and corticosterone. The results show that ACTH
      and corticosterone concentrations were elevated during sleep deprivation but
      returned to baseline within 4 h of recovery. After 1 day of sleep restriction,
      the ACTH and corticosterone response to restraint stress did not differ between
      control and sleep deprived rats. However, after 48 h of total sleep deprivation
      and after 8 days of restricted sleep, the ACTH response to restraint was
      significantly reduced whereas the corticosterone response was unaffected. These
      results show that sleep loss not only is a mild activator of the HPA axis itself,
      but also affects the subsequent response to stress. Alterations in HPA axis
      regulation may gradually appear under conditions of long total sleep deprivation
      but also after repeated sleep curtailment.

PMID- 12000546
TI  - Lesions of the posterior paraventricular thalamus block habituation of
      hypothalamic-pituitary-adrenal responses to repeated restraint.
AB  - We examined the role of the posterior division of the paraventricular nucleus of
      the thalamus (pPVTh) in habituation of hypothalamic-pituitary-adrenal (HPA)
      responses to repeated restraint. Habituation refers to the decrement in HPA
      activity that occurs with repeated exposure to the same or homotypic stressor. To
      date, the pPVTh has been shown to inhibit the enhanced or facilitated HPA
      responses to novel, heterotypic restraint in previously chronically cold stressed
      rats. We hypothesized that the pPVTh also inhibits HPA activity under conditions
      of habituation. In the first experiment, we lesioned the pPVTh and examined
      adrenocorticotropic hormone (ACTH) and corticosterone responses to the first or
      eighth restraint exposure. In sham-lesioned rats, we found lower ACTH and
      corticosterone responses to the eighth period of 30 min restraint compared to the
      first exposure, evidence for habituation. In pPVTh-lesioned rats, there was no
      difference in ACTH and corticosterone responses to the eighth compared to the
      first restraint exposure. Therefore, pPVTh lesions prevented the habituation of
      HPA responses to repeated restraint. In the second experiment, we examined
      whether habituation to restraint is observable in response to an acute, single
      restraint on day 28 in sham and pPVTh lesioned rats that were exposed to
      restraint only on days 1 through 8. In this experiment, we replicated the results
      from the first experiment, and found evidence that habituation to restraint can
      be observed weeks after chronic stress has been terminated. Furthermore, pPVTh
      lesions had no additional effects on HPA responses to acute stress on day 28. In
      summary, pPVTh lesions inhibit habituation of HPA activity to a homotypic
      stressor, without altering HPA responses to the first restraint. Thus, the intact
      pPVTh inhibits HPA activity under conditions of habituation, as well as
      facilitation, and represents an important regulator of HPA activity under
      conditions of chronic stress.

PMID- 12000547
TI  - Oestrogen regulates neurofilament expression in a subset of anterior pituitary
      cells of the adult female rat.
AB  - It is the prevailing view that the neurohypophysis derives from neural crest
      while the pituitary's anterior lobe is of ectodermal origin. However, it has been
      recently suggested that anterior pituitary cells could have in part neuro
      ectodermal origin, and thus should express specific neuronal markers. This issue
      was examined previously with conflicting results. The present study attempts to
      clarify the question of whether or not neuronal markers are expressed in the
      adenohypophysis. Using quantitative immunofluorescence, we have positively
      identified a subset of anterior pituitary cells, which express immunoreactivity
      for neuronal markers, including 68 kDa neurofilament (NF68). Interestingly, we
      noticed that the expression of NF68 is sexually dimorphic (i.e. neurofilament
      positive cells are more abundant in sexually mature female rats). In addition,
      NF68 expression in female rats increases during ontogenic development and reaches
      a plateau level after puberty. Thereafter, it displays plastic changes along the
      oestrous cycle, with the maximum of neurofilament expression at oestrus and the
      minimum at proestrus. NF68 immunoreactivity was examined after ovariectomy,
      oestradiol replacement and treatment with an specific oestrogen receptor
      antagonist. Bilateral ovariectomy induced a significant reduction in the number
      of NF68-positive cells. This effect was completely prevented by treatment of
      ovariectomized rats with oestradiol. When intact female rats were treated with
      the anti-oestrogen tamoxifen, a drastic decrease in NF68 expression in anterior
      pituitary cells was observed. Furthermore, oestradiol administration in castrated
      male rats increased NF68 immunoreactivity. Double-immunolabelling experiments
      provided evidence that pituitary cells expressing neuronal traits correspond to
      subsets of lactotrophs, somatotrophs, thyrotrophs and gonadotrophs. It remains to
      be established if NF68 induction in the pituitary is due to direct and/or
      indirect effects of oestrogens. Also, the possible functional role of this subset
      of NF68-positive anterior pituitary cells in the female rat remains to be
      examined.

PMID- 12000548
TI  - Neuroendocrinology briefings 16: genomic imprinting, hormones and behaviour.

PMID- 12000549
TI  - The distribution of caveolin-3 immunofluorescence in skeletal muscle fibre
      membrane defined by dual channel confocal laser scanning microscopy, fast Fourier
      transform and image modelling.
AB  - Membrane domains rich in caveolin-3 overlie sarcomeric actin in skeletal muscle.
      The membrane exhibits a regular array of caveolin-3 immunofluorescence using
      confocal laser scanning microscopy (CLSM). Fourier analysis of tissue imaged by
      CLSM accurately defines a repeating intensity with a long-axis spacing of 1.48
      microm confirmed by measurement of direct images. Reverse fast Fourier transform
      (FFT) and image-modelling allow reconstruction of the pattern. Mathematical
      modelling has allowed replication of several features of the FFT, including the
      second order maxima that confirm the relatively high information content of the
      original images. Measurements of membrane-pattern primary long-axis spacings are
      consistent with our measurements of the I-band sarcomere repeat in similarly
      prepared specimens labelled with fluorescent phalloidin or imaged using
      differential interference contrast microscopy. Dual-channel CLSM analysis of the
      sarcomeric banding pattern of actin and the repeating pattern of muscle fibre
      membrane caveolin showed that caveolae overlie the I-band. The anti-caveolin
      immunofluorescence is deficient over the Z-disc and maximal toward each of the I
      band extremities. A mechanism of membrane shape change in which membrane-lipid
      molecules are interposed between more stable anchored rafts associated with
      caveolae can be envisaged. Thus, increasing girth and reducing length of the
      sarcolemma in rapid contraction may be explained.

PMID- 12000550
TI  - The ELF -97 phosphatase substrate provides a sensitive, photostable method for
      labelling cytological targets.
AB  - We compared fluorescent signals obtained with fluorescein conjugates and the ELF
      97 (enzyme-labelled fluorescence) phosphatase substrate [2-(5'-chloro-2
      phosphoryloxyphenyl)-6-chloro-4(3H)-quinazolinone] in labelling cytological
      structures requiring high spatial resolution. Enzymatic cleavage of the ELF-97
      phosphatase substrate yields an extremely fine precipitate that remains well
      localized to the site of enzymatic activity. This precipitate fluoresces bright
      yellow-green, with maximal excitation at approximately 360 nm and maximal
      emission at approximately approximately 530 nm. The ELF substrate was used with
      streptavidin-alkaline phosphatase, to fluorescently label site-specific probes
      bound to their targets, including cell-surface sites, cytoplasmic organelles,
      nuclear antigens and cytoskeletal networks. All targets were labelled
      successfully with both the ELF substrate and fluoresceinated probes or protein
      conjugates. However, the ELF method was frequently more sensitive, with lower
      background fluorescence, allowing detection of more lysosomes, actin filaments,
      microtubules and nuclear targets than were visible with corresponding
      fluoresceinated probes. The ELF substrate was also used with antifluorescein
      alkaline phosphatase to amplify fluorescein signals. We found that the ELF signal
      was in all cases brighter and more photostable than fluorescein signals,
      permitting shorter film exposures and allowing more time for examining samples.
      Surprisingly, relative brightness and photostability depended on the target,
      rather than being a general phenomenon related to the choice of dye alone.

PMID- 12000551
TI  - Surface plasmon fluorescence microscopy: an analysis.
AB  - This paper examines the imaging performance of surface plasmon microscopes
      operating in the far field. Until recently the accepted view has been that the
      achievable lateral resolution with a surface plasmon imaging system is limited by
      propagation decay length of the surface plasmons rather than by diffraction. We
      show by simulation that the lateral resolution of a surface plasmon imaging
      system can be comparable to that of the best optical microscopes. We also show
      that new imaging modes such as two-photon and also second harmonic surface
      plasmon microscopy are extremely promising imaging modes that may be expected to
      be powerful techniques for the analysis of surface structures.

PMID- 12000552
TI  - Use of emission electron microscope for potential mapping in semiconductor
      microelectronics.
AB  - An emission electron microscope was used for visualization and measurement of the
      distribution of electric fields and potentials on the surface under study. The
      contrast of microfields is caused by the fact that slow-moving electrons emitted
      from the object surface are deflected by these fields. The measurements were
      performed on a p-n junction to which a voltage was applied. It is shown that the
      type of contrast from the p-n junction can be reversed depending on the position
      of the contrast aperture restricting the electron beam. The same result was
      obtained by means of a computer simulation.

PMID- 12000553
TI  - Light microscopy evaluation of polyurethane vascular grafts porosity by Sudan
      Black B staining.
AB  - In small-diameter vascular grafts, the porosity of the internal surface plays an
      important role because it affects initial thrombus deposition and therefore the
      graft's patency. As well as many other studies reported in the literature we have
      carried out a study of the relationship between porosity and the manufacturing
      parameters of polyurethane (PU) grafts by standard scanning electron microscopy
      (SEM) analysis. However, SEM was not completely satisfactory for evaluating the
      'sponge-like' uptake of water by the graft due to the unavoidable water loss and
      metal coating during preparation. In fact this preparation produces artefacts of
      the three-dimensional porous structure. To avoid this problem we investigated the
      possibility of observing the graft's internal surface through a stereomicroscope
      after it had absorbed water. We looked into a simple staining procedure which
      preferentially colours the PU graft fibres with respect to the void areas. After
      testing different kinds of stains, we eventually found that Sudan Black B, which
      usually stains for all kinds of lipid, turned out to be an excellent stain for
      the water-loaded PU grafts when diluted with ethanol. This staining procedure,
      coupled with a computerized image analysis system, allowed us to evaluate the
      degree of void and average void size of the graft internal surface and to
      correlate these data with graft density and manufacturing parameters.

PMID- 12000554
TI  - A new high-aperture glycerol immersion objective lens and its application to 3D
      fluorescence microscopy.
AB  - High-resolution light microscopy of glycerol-mounted biological specimens is
      performed almost exclusively with oil immersion lenses. The reason is that the
      index of refraction of the oil and the cover slip of approximately 1.51 is close
      to that of approximately 1.45 of the glycerol mountant, so that refractive index
      mismatch-induced spherical aberrations are tolerable to some extent. Here we
      report the application of novel cover glass-corrected glycerol immersion lenses
      of high numerical aperture (NA) and the avoidance of these aberrations. The new
      lenses feature a semi-aperture angle of 68.5 degrees, which is slightly larger
      than that of the diffraction-limited 1.4 NA oil immersion lenses. The glycerol
      lenses are corrected for a quartz cover glass of 220 microm thickness and for a
      80% glycerol-water immersion solution. Featuring an aberration correction collar,
      the lens can adapt to glycerol concentrations ranging between 72% and 88%, to
      slight variations of the temperature, and to the cover glass thickness. As the
      refractive index mismatch-induced aberrations are particularly important to
      quantitative confocal fluorescence microscopy, we investigated the axial
      sectioning ability and the axial chromatic aberrations in such a microscope as
      well as the image brightness as a function of the penetration depth. Whereas
      there is a significant decrease in image brightness associated with oil
      immersion, this decrease is absent with the glycerol immersion system. In
      addition, we show directly the compression of the optic axis in the case of oil
      immersion and its absence in the glycerol system. The unique advantages of these
      new lenses in high-resolution microscopy with two coherently used opposing
      lenses, such as 4 Pi-microscopy, are discussed.

PMID- 12000555
TI  - Rapid cryofixation of rabbit muscle fibres after a temperature jump.
AB  - We describe a procedure whereby structural changes that occur in muscle fibres
      after a rapid temperature jump can be captured by cryofixation. In the thick
      filament from rabbit and other mammalian skeletal muscles there is a rapid
      transition from a non-helical to a helical structure as the temperature is raised
      from 273 K towards physiological levels. This transition is accompanied by
      characteristic intensity changes in the X-ray diffraction pattern of the muscle.
      In our experiments to capture these changes, single fibres of glycerinated psoas
      muscle were subjected to a Joule temperature jump of 15-30 K from approximately
      278 K in air. We have developed a freezing method using a modified Gatan
      cryosnapper in which a pair of liquid nitrogen-cooled copper jaws were projected
      under pressure and closed on the fibre between 50 and 100 ms after the
      temperature jump. The frozen fibres were freeze-substituted and embedded for
      electron microscopy. Transverse and longitudinal sections of relaxed 'cold'
      (approximately 278 K) and temperature-jumped fibres as well as rigor fibres were
      obtained. Fourier transforms of the images from the three preparations showed
      differences in the relative intensities of the reflections from the hexagonal
      filament lattice and in those of the helix-based layer lines, similar to the
      differences seen by X-ray diffraction. We conclude that we have preserved the
      'hot' structure and that cryofixation is sufficiently fast to prevent the
      transition back to the 'cold' state.

PMID- 12000556
TI  - Multiphoton versus confocal high resolution z-sectioning of enhanced green
      fluorescent microtubules: increased multiphoton photobleaching within the focal
      plane can be compensated using a Pockels cell and dual widefield detectors.
AB  - Multiphoton excitation was originally projected to improve live cell fluorescence
      imaging by minimizing photobleaching effects outside the focal plane, yet reports
      suggest that photobleaching within the focal plane is actually worse than with
      one photon excitation. We confirm that when imaging enhanced green fluorescent
      protein, photobleaching is indeed more acute within the multiphoton excitation
      volume, so that whilst fluorescence increases as predicted with the square of the
      excitation power, photobleaching rates increase with a higher order relationship.
      Crucially however, multiphoton excitation also affords unique opportunities for
      substantial improvements to fluorescence detection. By using a Pockels cell to
      minimize exposure of the specimen together with multiple nondescanned detectors
      we show quantitatively that for any particular bleach rate multiphoton excitation
      produces significantly more signal than one photon excitation confocal microscopy
      in high resolution Z-axis sectioning of thin samples. Both modifications are
      readily implemented on a commercial multiphoton microscope system.

PMID- 12000557
TI  - Improving the quality of electron backscatter diffraction (EBSD) patterns from
      nanoparticles.
AB  - In this study, we investigated the relative contributions of atomic number (Z)
      and density (rho) to the degradation of the electron backscatter diffraction
      (EBSD) pattern quality for nanoparticles < 500 nm in diameter. This was
      accomplished by minimizing the diffuse scattering from the conventional thick
      mounting substrate through the design of a sample holder that can accommodate
      particles mounted on thin-film TEM substrates. With this design, the
      contributions of incoherently scattered electrons that result in the diffuse
      background are minimized. Qualitative and quantitative comparisons were made of
      the EBSD pattern quality obtained from Al(2)O(3) particles approximately 200 nm
      in diameter mounted on both thick- and thin-film C substrates. For the
      quantitative comparison we developed a 'quality' factor for EBSD patterns that is
      based on the ratio of two Hough transforms derived from a given EBSD pattern
      image. The calculated quality factor is directly proportional to the signal-to
      noise ratio for the EBSD pattern. In addition to the comparison of the thick and
      thin mounting substrates, we also estimated the effects of Z and rho by comparing
      the EBSD pattern quality from the Al(2)O(3) particles mounted on thin-film
      substrates with the quality of patterns obtained from Fe-Co nanoparticles
      approximately 120 nm in diameter. The results indicate that the increased
      background generated in EBSD patterns by the electrons escaping through the
      bottom of the small particles is the dominant reason for the poor EBSD pattern
      quality from nanoparticles < 500 nm in size. This was supported by the fact that
      we were able to obtain usable EBSD patterns from Al(2)O(3) particles as small as
      130 nm using the thin-film mounting method.

PMID- 12000558
TI  - Cation segregation in Nb16W18O94 using high angle annular dark field scanning
      transmission electron microscopy and image processing.
AB  - We report the characterization of the complex oxide Nb16W18O94 using high angle
      annular dark field imaging at 200 kV in a scanning transmission electron
      microscope. The results of this study suggest that the W and Nb cations are not
      uniformly distributed among the cation columns projected along [001] but that
      there is preferential segregation of the heavier species to certain column sites.
      In order to analyse the experimental data obtained, an image processing
      methodology has been developed which may also find application in locating
      specific motifs within a generally distorted image field.

PMID- 12000559
TI  - Axial tomographic confocal fluorescence microscopy.
AB  - By physical rotation of the sample, axial tomography enables the acquisition of
      otherwise inaccessible spatial information from an object. In combination with
      confocal microscopy, the method can fundamentally improve the effective three
      dimensional (3D) resolution. In this report we present a novel method for high
      resolution reconstruction of confocal axial tomographic data. The method
      automatically determines the relative angles of rotation, aligns the data from
      different rotational views and reconstructs a single high resolution 3D dataset.
      The reconstruction makes use of a known point spread function and is based on an
      unconstrained maximum likelihood deconvolution performed simultaneously from
      multiple (in our case three) angular views. It was applied to simulated as well
      as to experimental confocal datasets. The gain in resolution was quantified and
      the effect of choice of overrelaxation factors on the speed of convergence was
      investigated. A clearly improved 3D resolution was obtained by axial tomography
      together with reconstruction as compared with reconstruction of confocal data
      from only a single angular view.

PMID- 12000560
TI  - Comparison of the axial resolution of practical Nipkow-disk confocal fluorescence
      microscopy with that of multifocal multiphoton microscopy: theory and experiment.
AB  - We compare the axial sectioning capability of multifocal confocal and multifocal
      multiphoton microscopy in theory and in experiment, with particular emphasis on
      the background arising from the cross-talk between adjacent imaging channels. We
      demonstrate that a time-multiplexed non-linear excitation microscope exhibits
      significantly less background and therefore a superior axial resolution as
      compared to a multifocal single-photon confocal system. The background becomes
      irrelevant for thin (< 15 microm) and sparse fluorescent samples, in which case
      the confocal parallelized system exhibits similar or slightly better sectioning
      behaviour due to its shorter excitation wavelength. Theoretical and experimental
      axial responses of practically implemented microscopes are given.

PMID- 12000561
TI  - Simultaneous phase and amplitude extraction from a single defocused image of a
      homogeneous object.
AB  - We demonstrate simultaneous phase and amplitude extraction from a single
      defocused image of a homogeneous object. Subject to the assumptions explicitly
      stated in the derivation, the algorithm solves the twin-image problem of in-line
      holography and is capable of analysing data obtained using X-ray microscopy,
      electron microscopy, neutron microscopy or visible-light microscopy, especially
      as they relate to defocus and point projection methods. Our simple, robust, non
      iterative and computationally efficient method is applied to data obtained using
      an X-ray phase contrast ultramicroscope.

PMID- 12000562
TI  - Automated reconstruction of curvilinear fibres from 3D datasets acquired by X-ray
      microtomography.
AB  - The characterization of fibrous structures is important in both composites and
      textiles research for relating to the bulk properties of the material. However,
      the microscopic nature of the fibres and their high densities make them very
      difficult to characterize. Many techniques have been developed for the
      measurement and characterization of fibrous structures but they tend to be
      restricted to measurements on the sample surface or within physical cross
      sections. X-ray microtomography can be used to non-destructively probe the
      internal structure of a range of fibrous materials, providing large amounts of 3D
      data. A technique has been developed for tracing fibres within 3D datasets
      acquired by X-ray microtomography and this has been applied to a glass fibre
      reinforced composite and also a non-woven textile sample. The 3D fibrous
      structures of both samples were successfully reconstructed and their fibre
      orientation distributions calculated. This technique enables novel
      characterizations, such as the through-thickness variation of fibre orientation
      in non-wovens.

PMID- 12000563
TI  - Stereological length estimation using spherical probes.
AB  - Lineal structures in biological tissue support a wide variety of physiological
      functions, including membrane stabilization, vascular perfusion, and cell-to-cell
      communication. In 1953, Smith and Guttman demonstrated a stereological method to
      estimate the total length density (Lv) of linear objects based on random
      intersections with a two-dimensional sampling probe. Several methods have been
      developed to ensure the required isotropy of object-probe intersections,
      including isotropic-uniform-random (IUR) sections, vertical-uniform-random (VUR)
      slices, and isotropic virtual planes. The disadvantages of these methods are the
      requirements for inconvenient section orientations (IUR, VUR) or complex counting
      rules at multiple focal planes (isotropic virtual planes). To overcome these
      limitations we report a convenient and straightforward approach to estimate Lv
      and total length, L, for linear objects on tissue sections cut at any arbitrary
      orientation. The approach presented here uses spherical probes that are
      inherently isotropic, combined with unbiased fractionator sampling, to
      demonstrate total L estimation for thin nerve fibres in dorsal hippocampus of the
      mouse brain.

PMID- 12000564
TI  - Adaptive correction of depth-induced aberrations in multiphoton scanning
      microscopy using a deformable mirror.
AB  - We demonstrate adaptive aberration correction for depth-induced spherical
      aberration in a multiphoton scanning microscope with a micromachined deformable
      mirror. Correction was made using a genetic learning algorithm with two-photon
      fluorescence intensity feedback to determine the desired shape for an adaptive
      mirror. For a 40x/0.6 NA long working distance objective, the axial scanning
      range was increased from 150 mm to 600 mm.

PMID- 12000565
TI  - A new surface characterization technique: RIMAPS (Rotated Image with Maximum
      Average Power Spectrum).
AB  - This work introduces a new imaging technique, Rotated Image with Maximum Average
      Power Spectrum (RIMAPS), for use in determining orientation and characteristics
      of surface topography. It consists of computing the maximum value of the averaged
      power spectrum, given by one step of the two-dimensional Fourier transform, for
      each angle of rotation of a digitized image. The basic measurement science of
      this technique is described and different cases are studied. The characterization
      of simple geometrical figures explains the meaning of peaks and their angular
      positions given by RIMAPS analysis. A known surface pattern made on a sample of
      pure copper, mechanically ground, is used to study reproducibility, dependence on
      image quality and topography scale relative to pixel size and magnification.
      Samples of pure zinc, mechanically ground and chemically etched, were used to
      show the main features of RIMAPS analysis when characterizing a more complicated
      pattern on a real surface. All the studies performed under different conditions
      for observation and acquisition of images give strong evidence of the stability
      and robustness of RIMAPS as a technique for the characterization of topography.

PMID- 12000566
TI  - Minimizing scanning electron microscope artefacts by filter design.
AB  - A new type of non-linear filter for digital images has been developed. By using
      distance transforms we estimate the average point spread function for a set of
      fibre cross-sectional images. Then a fast filter technique, based on lookup
      tables for distance layers, attenuates the uneven background response from the
      scanning electron microscope. Compared to the convolution-based techniques that
      we tried, this approach caused less blurring effects on our fibre images and also
      made the background pixels more homogeneous. The only assumption we make is that
      we can roughly segment the background pixels by using a pixel-wise classifier.
      Although the assumption that the uneven background response can be described by a
      circular point spread function is only approximately true in the case discussed
      here, this method greatly attenuates the effect and provides a fast and general
      filtering method that can also be of use for other applications.

PMID- 12000580
TI  - Health characteristics and health services utilization in older adults with
      intellectual disability living in community residences.
AB  - BACKGROUND: The health status and health needs of adults with intellectual
      disability (ID) change with advancing age, and are often accompanied by
      difficulties with vision, hearing, mobility, stamina and some mental processes.
      AIM: The present study collected health status information on a large cohort of
      adults with ID aged > or = 40 years living in small group, community-based
      residences in two representative areas of New York State, USA. METHOD: Adult
      group home residents with ID aged between 40 and 79 years (n = 1371) were
      surveyed to determine their health status and patterns of morbidity. RESULTS:
      Most subjects were characterized as being in good health. The frequency of
      cardiovascular, musculoskeletal and respiratory conditions, and sensory
      impairments increased with age, while neurological, endocrine and dermatological
      diseases did not. Psychiatric and behavioural disorders declined with increasing
      age, at least through 70 years of age. Although most conditions increased with
      age, their frequency varied by sex and level of ID. Frequencies of age-related
      organ system morbidity were compared to data from the National Health and
      Nutrition Evaluation Survey III. It was found that adults with ID had a lower
      overall reported frequency of cardiovascular risk factors, including hypertension
      and hyperlipidaemia, and adult-onset diabetes. Inconsistencies with mortality
      data among older adults with ID were observed (which showed equal if not greater
      prevalence of deaths as a result of cardiovascular disease and cancer).
      CONCLUSION: These results suggest that either a cohort effect is operating (i.e.
      contemporary populations are healthier than previous populations), or that there
      may be under-recognition of select risk factors and diseases.

PMID- 12000581
TI  - Prevalence, morbidity and service need among South Asian and white adults with
      intellectual disability in Leicestershire, UK.
AB  - BACKGROUND: Previous reports have suggested that South Asian and white UK
      populations have different prevalences of intellectual disability (ID), related
      psychological morbidity and service use. The aim of the present study was to
      compare these rates among South Asian and white adults in Leicestershire, UK.
      METHOD: This cross-sectional study is comprised of two parts. The analysis of
      prevalence is based on data from all South Asian and white adults known to the
      Leicestershire Learning Disabilities Register in 1991, with population
      denominators being drawn from the 1991 census. The other analyses use data
      collected from the most recent semi-structured home interviews, carried out
      between 1987 and 1998, with 206 South Asian and 2334 white adults. RESULTS: The
      prevalence of ID in adults in Leicestershire is 3.20 per 1000 in South Asians and
      3.62 per 1000 in whites. Among adults with ID, South Asians have similar
      prevalences of disabilities to whites and significantly lower skill levels. South
      Asians show similar levels of psychological morbidity, but make significantly
      lower use than whites of psychiatric services, residential care and respite care.
      South Asians use community services as extensively as whites, but feel that they
      have a substantially greater unmet need, especially with regard to social
      services. CONCLUSION: South Asian and white populations have similar prevalences
      of ID and related psychological morbidity. Culturally appropriate services for
      South Asian adults may need to focus on skill development and community care.

PMID- 12000582
TI  - Utilization of medical care among children with Down's syndrome.
AB  - BACKGROUND: The present authors have previously found an increased mortality rate
      in children with Down's syndrome (DS) and a congenital heart defect (CHD). The
      aim of the present study was to investigate the utilization of medical care in
      relation to congenital malformations in DS. METHOD: Retrospectively, 211 children
      with DS born between 1973 and 1980 in the northern part of Sweden were followed
      up for at least 17 years (1973-1997). The duration of neonatal care was compared
      with that of children with DS born between 1995 and 1998 in the same region.
      RESULTS: Neonatal care was reduced over time. Almost 50% of the children had CHD,
      and before 10 years of age, these subjects were admitted for inpatient care twice
      as often as children with DS who did not have malformations, and had more than 12
      times as many inpatient days per month. The existence of a gastrointestinal or
      other malformation increased inpatient days per month four and two times,
      respectively, compared to healthy children with DS. During the first 10 years of
      life, children with DS and a CHD accounted for 71% of all inpatient days caused
      by infections. No gender differences were observed. CONCLUSIONS: At a group
      level, the presence of a CHD was the most important congenital abnormality in
      determining utilization of medical care and the burden of infections in the
      population of children with DS.

PMID- 12000583
TI  - Benefits of the Treatment and Education of Autistic and Communication Handicapped
      Children (TEACCH) programme as compared with a non-specific approach.
AB  - BACKGROUND: Two educational treatments were compared, the Treatment and Education
      of Autistic and Communication Handicapped Children (TEACCH) programme and the
      integration programme for individuals with disabilities. METHODS: Two groups of
      eight subjects were matched by gender, chronological and mental age, and
      nosographic diagnosis (i.e. autism associated with severe intellectual
      disability, DSM-IV criteria and Childhood Autism Rating Scale scored. The TEACCH
      programme was applied to the experimental group, while the control group was
      integrated in regular schools with a support teacher. The Psycho-Educational
      Profile-Revised and the Vineland Adaptive Behaviour Scale were administered twice
      with a one-year interval between assessments. RESULTS: The scores of the
      experimental group increased more than the control group scores. Statistically
      significant differences were obtained in both groups because of the differences
      in the two approaches.

PMID- 12000584
TI  - Family environment and cognitive abilities in girls with fragile-X syndrome.
AB  - BACKGROUND: There remains some variance in cognitive ability that is unexplained
      in children with fragile-X syndrome (FXS). Studies in typically developing
      children suggest that family environment might be one contributor to this
      unexplained variance. However, the effect of family environment in relation to
      cognition in atypical children with FXS has been relatively unexplored to date.
      METHODS: The present authors examined the putative genetic and environmental
      factors associated with cognition in a group of age-matched children consisting
      of 26 females with FXS and 31 typically developing children. All subjects were
      administered the Wechsler Intelligence Scale for Children-Revised; and the
      subjects' parents were administered the Wechsler Adult Intelligence Scale
      Revised, and completed the Hollingshead Index of Social Status and the Moos &
      Moos Family Environment Scale. RESULTS: Using a multiple regression analytic
      strategy, the present authors found that family environment contributed
      significantly to cognitive abilities in typically developing girls, but did not
      have a unique contribution to cognitive abilities in girls with FXS. There was a
      suggestion that, for girls with FXS, socio-economic status, a measure of
      sociocultural environment, was correlated with IQ. CONCLUSIONS: The present study
      provides a basis for future research on the environmental contributions to
      cognitive abilities, particularly work related to verbal cognition.

PMID- 12000585
TI  - Difficulties in conducting a randomized controlled trial of health service
      interventions in intellectual disability: implications for evidence-based
      practice.
AB  - BACKGROUND: In an era of evidence-based medicine, practice is constantly
      monitored for quality in accordance with the needs of clinical governance
      (Oyebode et al. 1999). This is likely to lead to a dramatic change in the
      treatment of those with intellectual disability (ID), in which evidence for
      effective intervention is limited for much that happens in ordinary practice. As
      Fraser (2000, p. 10) has commented, the word that best explains "the
      transformation of learning disability practice in the past 30 years is
      'enlightenment'." This is not enough to satisfy the demands of evidence, and
      Fraser exhorted us to embrace more research-based practice in a subject that has
      previously escaped randomized controlled trials (RCTs) of treatment because of
      ethical concerns over capacity and consent, which constitute a denial of
      opportunity which "is now at last regarded as disenfranchising". CONCLUSIONS: The
      present paper describes the difficulties encountered in setting up a RCT of a
      common intervention, i.e. assertive community treatment, and concludes that a
      fundamental change in attitudes to health service research in ID is needed if
      proper evaluation is to prosper.

PMID- 12000586
TI  - Evaluating the use of multiple microswitches and responses for children with
      multiple disabilities.
AB  - BACKGROUND: The present study assessed the feasibility of (1) establishing
      multiple microswitches and responses (some of which had not been used before)
      with two children with multiple disabilities, and (2) maintaining such
      microswitches and responses in the children's daily contexts. METHODS: The
      microswitches were introduced individually and then combined. During the last
      part of treatment and the follow-up, each child had three microswitches. RESULTS:
      The data show that both children learned to use all three available
      microswitches. Moreover, they retained fairly high levels of responding with the
      microswitches in their daily contexts during follow-up periods of 4 and 6 months.
      CONCLUSIONS: The personal and practical implications of these findings are
      discussed.

PMID- 12000587
TI  - Social timing, clock genes and autism: a new hypothesis.
AB  - BACKGROUND: Timing and social timing deficits are fundamental in autism and may
      play a developmental role in its manifestation. Sleep problems are associated
      with this disorder, as is a reduction or loss of Purkinje cells associated with
      regions of the brain which co-ordinate fine motor movements. Genetic studies
      suggest that a number of genes of limited effect lead to autism and that the
      genes are epistatic. CONCLUSIONS: We suggest that anomalies in clock genes
      operating as timing genes in high frequency oscillator systems may underlie the
      timing deficits of autism. We outline how anomalies in methylation-related genes
      may also be implicated.

PMID- 12000588
TI  - Response to Reinders J.S. Absence of evidence is not evidence of absence. Journal
      of Intellectual Disability Research, 46(2), 187-90.

PMID- 12000590
TI  - Disorders of gastrointestinal motility: towards a new classification.

PMID- 12000591
TI  - Guidelines for the management of acute pancreatitis.

PMID- 12000592
TI  - Clinical features, etiology, and survival of hepatocellular carcinoma among
      different countries.

PMID- 12000593
TI  - Setting standards for colonoscopic teaching and training.

PMID- 12000594
TI  - Guideline for the management of acute diarrhea in adults.

PMID- 12000595
TI  - Health-related quality of life and gastrointestinal disease.
AB  - Society is changing rapidly, and new aspects need to be considered when
      evaluating treatment of disease. Health-related quality of life (HRQL) is a
      relatively new addition to the tools clinicians use to gain a better
      understanding of the impact of disease and its treatment. The questions 'What is
      it?', 'How it is measured?' and 'How can the information be used?' are now better
      understood than a few years ago. Generic instruments to capture HRQL enable a
      broad assessment of a range of aspects and can be used to make comparisons
      between different patient populations. Irrespective of the choice of instrument,
      they can classify the influence of different factors, such as gender, age,
      general health status and disease severity. Health-related quality of life
      assessments have been made in many areas of gastroenterology, such as reflux
      disease, inflammatory bowel disease and irritable bowel syndrome, to describe the
      burden of illness and the impact of treatment. Health-related quality of life as
      a prediction of treatment response is another interesting option. Its ability in
      the context of surgical intervention and outcomes is also emerging even though
      more work must be done in this area. Health-related quality of life evaluations,
      as an additional tool in the management of patients, are here to stay.

PMID- 12000596
TI  - New optical technologies for earlier endoscopic diagnosis of premalignant
      gastrointestinal lesions.
AB  - Gastrointestinal malignancies continue to be the second leading cause of cancer
      related deaths in the developed world. The early detection and treatment of
      gastrointestinal preneoplasms has been demonstrated to significantly improve
      patient survival. Conventional screening tools include standard white light
      endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic
      surveillance biopsy protocols aimed at early detection of dysplasia and
      malignancy have been undertaken for groups at high risk. Unfortunately, the poor
      sensitivity associated with WLE is a significant limitation. In this regard,
      major efforts continue in the development and evaluation of alternative
      diagnostic techniques. This review will focus on notable developments made at the
      forefront of research in modern gastrointestinal endoscopy based on novel optical
      endoscopic modalities, which rely on the interactions of light with tissues. Here
      we present the 'state-of-the-art' in fluorescence endoscopic imaging and
      spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering
      spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and
      immunofluorescence endoscopy. These new developments may offer significant
      improvements in the diagnosis of early lesions by allowing for targeted mucosal
      excisional biopsies, and perhaps may even provide 'optical biopsies' of
      equivalent histological accuracy. This enhancement of the endoscopist's ability
      to detect subtle preneoplastic changes in the gastrointestional mucosa in real
      time and improved staging of lesions could lead to curative endoscopic ablation
      of these lesions and, in the long term, improve patient survival and quality of
      life.

PMID- 12000597
TI  - Hepatic transport systems.
AB  - The identification of the genes responsible for various genetic liver disorders
      lead to a better understanding of basic physiology of hepatic transport systems.
      In this review we focus on transport systems involved in the generation of bile
      and in the maintenance of copper homeostasis. Abnormal function of these
      transporters results in diseases like Wilson's disease, progressive familial
      cholestasis syndromes, Dubin-Johnson syndrome and cystic fibrosis. Beyond these
      well defined diseases, functional impairments of transport proteins may
      predispose to non-genetic diseases ranging from intrahepatic cholestasis of
      pregnancy to neurodegenerative disorders including Alzheimer's disease.

PMID- 12000598
TI  - The prevention and treatment of dysplasia in gastroesophageal reflux disease: The
      results and the challenges ahead.

PMID- 12000599
TI  - Management of viral hepatitis B.
AB  - Hepatitis B virus (HBV) infection is a major global health concern and is the
      most common cause of chronic liver disease worldwide. The natural history and
      clinical outcomes of chronic HBV infection are determined by the viral
      replication cycle and the host immune responses. Treatment of chronic hepatitis B
      is directed at interrupting the natural history by suppressing HBV replication
      before development of any significant irreversible liver cell damage. Effective
      antiviral therapies should be followed by sustained suppression of HBV-DNA,
      normalization of transaminases levels and a stable stage of HBeAg seroconversion
      with persistence of circulating anti-HBeAg antibodies. Two major classes of
      antiviral therapeutic agents that have been approved for treatment of chronic
      hepatitis B are immunomodulating agents (i.e. interferon) and the nucleoside
      analogs (i.e. lamivudine). A 4-6 month course of interferon-alpha has resulted in
      improvement of survival in 20%-30% of patients with chronic hepatitis B who had
      elevated serum ALT levels without hepatic decompensation. Interferon-alpha
      therapy is associated with HBeAg seroconversion; normalization of ALT levels,
      reduced hepatic inflammation, and possibly reduced disease progression to
      cirrhosis and hepatocellular carcinoma. Interferon can also be used with caution
      in patients with early compensated cirrhosis. A 12-month course of lamivudine has
      been shown to be well tolerated and effective. Lamivudine can be used in
      decompensated cirrhosis and immunosuppressed patients and for prevention of
      recurrent HBV infection after liver transplantation. The response rates after 3
      years of lamivudine therapy account for 40-65%. A major problem of antiviral
      treatment is the emergence of drug resistance conferred by mutations in the YMDD
      motif of HBV reverse transcriptase. The prevalence of YMDD mutations increases
      with longer durations of antiviral therapies and this has been detected in 20% of
      immunocompetent patients receiving lamivudine per year. Contentious issues remain
      when to stop the treatment if HBeAg seroconversion does not occur. Many new
      immunomodulatory therapies and antiviral agents are in various stages of clinical
      development and have shown some promise. Among newer HBV antivirals, adefovir
      dipivoxil, entecavir, emtricitabine, DAPD and clevudine appear to be at least as
      potent as lamivudine in suppressing HBV replication. In vitro studies have shown
      that YMDD mutations confer cross-resistance between lamivudine and emtricitabine.
      However, adefovir, dipivoxil, lobucavir, DAPD and possibly clevudine suppress
      replications of both YMDD mutants and wild types of HBV. Immunomodulatory
      approaches for treatment of chronic hepatitis B are conceptually attractive, but
      newer agents used to date (thymosin-alpha, interleukin-12, therapeutic vaccines)
      have not demonstrated sufficient efficacy for widespread use. Combinations of an
      immunomodulatory agent and nucleoside analog may improve the therapeutic efficacy
      and reduce the emergence of drug resistance. Nevertheless, combinations of
      interferon and lamivudine therapies do not confer such additional benefits. The
      next challenge for HBV treatment is to use antivirals in combination and/or in
      cyclical therapy to minimize the emergence of drug resistance and increase
      efficacy, particularly to achieve sustainable post-treatment suppression of HBV.
      Randomized prospective control trials of combined antiviral therapies given
      simultaneously or sequentially are needed to establish safe and effective
      combined regimens that can be recommended for future treatment strategies.

PMID- 12000600
TI  - Management of viral hepatitis C.
AB  - The hepatitis C virus was first identified in 1989. It causes chronic hepatitis,
      cirrhosis and hepatocellular carcinoma. Global anti-HCV prevalence is 1-3%.
      Contaminated blood product, dirty needles and instruments, and injection drug use
      are the main parenteral routes of transmission. Cultural practices, such as
      acupuncture, tattoo, body piercing and scarring, also play a role. Universal
      precaution is the mainstay for prevention before vaccine is developed. Therapy
      for chronic hepatitis C (CHC) with interferon (IFN) is not satisfactory. Non
      response and early relapse reduce sustained response (SR). In 1997, National
      Institute of Health consensus recommended IFN therapy only for selected patients
      with compensated CHC, raised ALT and moderate to severe histologic disease
      activity; 15-20% SR is expected. Major advances in CHC therapy is combination
      therapy. Ribavirin in combination with IFN significantly increases SR to 30-40%.
      Even patients with high viral load, genotype 1, significant fibrosis or cirrhosis
      respond better. EASL and APASL Consensus in 1999 recommended IFN-ribavirin
      combination as the first line therapy. Recent data on pegylated IFN showed very
      encouraging results. Combined with ribavirin, 60% SR was achieved. It benefits
      patients with severe bridging necrosis and also cirrhosis. However, 23-27% of
      patients receiving combination therapy with either IFN type, experienced adverse
      events and required therapy discontinuation. Many important issues remained
      unsolved. Therapy for children, the elderly, patients with comorbidity and extra
      hepatic syndromes need to be addressed. Therapy is too expensive and not
      affordable to the majority of patients in developing countries.

PMID- 12000601
TI  - Epidemiology and prophylaxis of viral hepatitis: a global perspective.
AB  - BACKGROUND: Viral hepatitis with various forms of acute and chronic liver disease
      as potential and ultimately fatal sequelae presents a public health problem
      worldwide. METHODS: Recent published reports on the global epidemiology and
      prophylaxis of viral hepatitis were reviewed. RESULTS: With the advances in novel
      technologies, eight distinct types of hepatitis virus have been described:
      Hepatitis A, B, C, D, E, G, TT and SEN viruses. Hepatitis A and E viruses are
      transmitted by the fecal-oral route and do not induce a chronic carrier state.
      Due to major changes in epidemiology of hepatitis A virus their significance is
      more pronounced in areas of intermediate endemicity. Since the available
      hepatitis A vaccine is rather expensive, cost-benefit studies should be performed
      with emphasis on the area under consideration or specialized vulnerable groups.
      Parenterally transmitted hepatitis B and C viruses are major causes of chronic
      liver disease, including cirrhosis, hepatocellular carcinoma and end-stage liver
      failure. Hepatitis D virus is unable to replicate on its own, it requires an
      established hepatitis B virus infection to be able to replicate. Since its
      introduction, hepatitis B vaccine has been widely used leading to a significant
      decrease in HBV infection in countries with universal vaccination. Hepatitis G
      and TT viruses have been characterized within the latter part of the past decade
      but their significance as to the causation of human liver disease has yet to be
      elucidated. Likewise, the precise impact of the most recently described SEN virus
      isolated from patients with post-transfusion hepatitis awaits further studies.
      CONCLUSIONS: In the course of this review, we present the situation and focus on
      research activities emphasizing epidemiology and prevention of the various forms
      of viral hepatitis.

PMID- 12000602
TI  - Predictors of surgical outcomes.
AB  - The foundation of surgical decision-making has always been the risk-to-benefit
      ratio. Traditionally, the risks of complications and death, predicted by comorbid
      conditions, have been balanced against the benefits of disease management; that
      is, relief of symptoms or prevention of disease-related complications.
      Increasingly, patient preference and quality-of-life outcomes are entering into
      the decision-making process even at the price of modest increases in risk. In
      addition, the role of the surgeon as a predictor of outcomes has come under close
      scrutiny and has been demonstrated as having an effect on a number of important
      surgical outcomes. In the future, our methods for analyzing and reporting
      surgical outcomes will have to accommodate new predictors.

PMID- 12000603
TI  - Predictive factors for success of neo-adjuvant therapy in upper gastrointestinal
      cancer.
AB  - BACKGROUND: Predicting response to treatment has long been the Holy Grail of
      clinicians treating patients with upper gastrointestinal malignancy. The
      widespread use of neoadjuvant therapy for esophageal cancer has provided an added
      urgency to the issue and at the same time brought success a step closer because
      accurate response can be determined from analysis of the resected specimen.
      METHODS: A search was undertaken of the Medline database for text references to
      neoadjuvant therapy, esophagus, stomach and predicting response. The references
      of these publications were further scanned for appropriate references in the text
      and reference lists. RESULTS: Publications describing predictive markers to
      neoadjuvant therapy for esophageal cancer, which were most likely to be of
      clinical significance, were selected for inclusion in this report. CONCLUSIONS:
      The most reliable tissue markers of response based on analysis of pretreatment
      biopsy specimens include P53, Ki-67, EGFR and the most impressive serum marker
      for monitoring response are CYFRA 21-1 and CEA. The results, however, are
      inconsistent, and the markers of relatively low sensitivity and none reliably
      identifies individual patients who will respond.

PMID- 12000604
TI  - A critical assessment of new therapies in inflammatory bowel disease.
AB  - The only therapy in inflammatory bowel disease (IBD), which up to the mid-1990s
      was disease modifying, was immunosuppression with azathioprine. Other 'standard'
      therapies in IBD were merely symptomatic. With the advent of biological
      therapies, especially the chimeric monoclonal anti-TNF antibody infliximab, we
      start to target specific pathogenic disease mechanisms, which allow thorough
      suppression of the disease process and healing of the bowel in the long term.
      Moreover, infliximab is the only drug up to the present that allows short-term
      healing of fistulizing Crohn's disease. This therapy is, however, associated with
      problems of immunogenicity. The formation of antibodies to infliximab jeopardizes
      the efficacy and is associated with infusion reactions. Optimization of anti-TNF
      strategies will occur in the coming years. Another promising therapy is
      antagonization of alpha4 integrins and hence, of migration of inflammatory cells
      to the intestine. It can be expected that more simple therapies using small
      molecules that inhibit the key cytokines or pro-inflammatory processes will take
      over in the next decade. In the current and future approach to IBD therapy
      immunosuppression with azathioprine or 6-MP and methotrexate play a central role.
      At the present time, the combination of infliximab with azathioprine or
      methotrexate can be regarded as the new standard for the therapy of refractory
      Crohn's disease. In ulcerative colitis (UC) much less progress has been made and
      the value of biological therapy as well as of long-term management with
      immunosuppression remains controversial. Probiotics are an attractive treatment
      option for IBD but studies so far are small and data are not yet convincing.

PMID- 12000605
TI  - Non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects
      a high proportion of the world's population. Insulin resistance and oxidative
      stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical
      and imaging studies are of value in the diagnostic evaluation of patients with
      NAFLD, but liver biopsy remains the most sensitive and specific means of
      providing important diagnostic and prognostic information. Simple steatosis has
      the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to
      progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical
      therapy is currently available for all patients with NAFLD. In patients with
      diabetes mellitus and hyperlipidemia, appropriate metabolic control is always
      recommended, but rarely effective in resolving the liver disease. Weight
      reduction, when achieved and sustained, may improve the liver disease, although
      the results with weight loss have been inconsistent. Pharmacological therapy
      aimed at the underlying liver disease holds promise. Several medications with
      different mechanisms of action and potential benefit are currently being
      evaluated in clinical trials. Liver transplantation is a life-extending
      therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur
      after liver transplantation.

PMID- 12000606
TI  - Hereditary hemochromatosis and iron overload diseases.

PMID- 12000607
TI  - Antibiotic and biocide resistance in bacteria: introduction.
AB  - Drug resistance in bacteria is increasing and the pace at which new antibiotics
      are being produced is slowing. It is now almost commonplace to hear about
      methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
      enterococci (VRE), multi-drug resistance in Mycobacterium tuberculosis (MDRTB)
      strains and multi-drug-resistant (MDR) Gram-negative bacteria. So-called new and
      emerging pathogens add to the gravity of the situation. Reduced susceptibility to
      biocides is also apparently increasing, but is more likely to be low level in
      nature and to concentrations well below those used in hospital, domestic an
      industrial practice. A particular problem, however, is found with bacteria and
      other micro-organisms present in biofilms, where a variety of factors can
      contribute to greater insusceptibility compared with cells in planktonic culture.
      Also of potential concern is the possibility that widespread usage of biocides is
      responsible for the selection and maintenance of antibiotic-resistant bacteria.
      The basic mechanisms of action of, and bacterial resistance to, antibiotics are
      generally well documented, although data continue to accumulate about the nature
      and importance of efflux systems. In contrast, the modes of action of most
      biocides are poorly understood and consequently, detailed evaluation of bacterial
      resistance mechanisms is often disappointing. During this Symposium, the
      mechanisms of bacterial resistance to antibiotics and biocides are discussed at
      length. It is hoped that this knowledge will be used to develop newer, more
      effective drugs and biocides that can be better and perhaps, on occasion, more
      logically used to combat the increasing problem of bacterial resistance.

PMID- 12000608
TI  - Exploiting current understanding of antibiotic action for discovery of new drugs.
AB  - The introduction of antibiotics for the chemotherapy of bacterial infections has
      been one of the most important medical achievements of the past 50 years.
      However, the emergence of bacterial resistance to antibiotics undermines the
      therapeutic utility of existing agents, creating a requirement for the discovery
      of new antibacterial drugs. Several drug discovery strategies have emerged,
      including incremental improvements to existing antibiotics by chemical
      manipulation and the search for novel drug targets based on genomic approaches.
      An alternative strategy seeks to exploit opportunities for drug discovery arising
      from an understanding of the mode of action of existing antibiotics. Thus
      biochemical pathways or processes inhibited by antibiotics already in clinical
      use may nevertheless contain key functions that represent unexploited targets for
      further drug discovery. A major benefit of employing pathways or processes that
      are already known to contain drug targets is that proof of principle for drug
      intervention is already established. This approach to drug discovery is
      illustrated by reviewing target sites for existing antibiotics and considering
      how this information might be applied for the discovery of new agents inhibiting
      peptidoglycan synthesis, tRNA synthesis, transcription and DNA replication

PMID- 12000609
TI  - Bacterial target sites for biocide action.
AB  - Although biocides have been used for a century, the number of products containing
      biocides has recently increased dramatically with public awareness of hygiene
      issues. The antimicrobial efficacy of biocides is now well documented; however,
      there is still a lack of understanding of their antimicrobial mechanisms of
      action. There is a wide range of biocides showing different levels of
      antimicrobial activity. It is generally accepted that, in contrast to
      chemotherapeutic agents, biocides have multiple target sites within the microbial
      cell and the overall damage to these target sites results in the bactericidal
      effect. Information about the antimicrobial efficacy of a biocide (i.e. the eta
      value) might give some useful indications about the overall mode of action of a
      biocide. Bacteriostatic effects, usually achieved by a lower concentration of a
      biocide, might correspond to a reversible activity on the cytoplasmic membrane
      and/or the impairment of enzymatic activity. The bacteriostatic mechanism(s) of
      action of a biocide is less documented and a primary (unique?) target site within
      the cell might be involved. Understanding the mechanism(s) of action of a biocide
      has become an important issue with the emergence of bacterial resistance to
      biocides and the suggestion that biocide and antibiotic resistance in bacteria
      might be linked. There is still a lack of understanding of the mode of action of
      biocides, especially when used at low concentrations (i.e. minimal inhibitory
      concentration (MIC) or sublethal). Although this information might not be
      required for highly reactive biocides (e.g. alkylating and oxidizing agents) and
      biocides used at high concentrations, the use of biocides as preservatives or in
      products at sublethal concentrations, in which a bacteriostatic rather than a
      bactericidal activity is achieved, is driving the need to better understand
      microbial target sites. Understanding the mechanisms of action of biocides serves
      several purposes: (i) it will help to design antimicrobial formulations with an
      improved antimicrobial efficacy and (ii) it will ensure the prevention of the
      emergence of microbial resistance.

PMID- 12000610
TI  - Novel targets for the future development of antibacterial agents.
AB  - Recent advances in DNA sequencing technology have made it possible to elucidate
      the entire genomes of pathogenic bacteria, and advancements in bioinformatic
      tools have driven comparative studies of these genome sequences. These
      evaluations are dramatically increasing our ability to make valid considerations
      of the limitations and advantages of particular targets based on their predicted
      spectrum and selectivity. In addition, developments in gene knockout technologies
      amenable to pathogenic organisms have enabled new genes and gene products
      critical to bacterial growth and pathogenicity to be uncovered at an
      unprecedented rate. Specific target examples in the areas of cell wall
      biosynthesis, aromatic amino acid biosynthesis, cell division, two component
      signal transduction, fatty acid biosynthesis, isopreniod biosynthesis and tRNA
      synthetases illustrate how aspects of the above capabilities are impacting on the
      discovery and characterization of novel antibacterial targets. An example of a
      novel inhibitor of bacterial fatty acid biosynthesis discovered from high
      throughput screening processes is described, along with its subsequent chemical
      optimization. Furthermore, the application and importance of technologies for
      tracking the mode of antibacterial action of these novel inhibitors is discussed.

PMID- 12000611
TI  - Cellular impermeability and uptake of biocides and antibiotics in Gram-negative
      bacteria.
AB  - The principal targets for antibacterial agents reside at the cytoplasm and
      cytoplasmic membrane, damage to other structures often arising from initial
      events at these loci. The Gram-negative bacteria offer a complex barrier system
      to biocides and antibiotics, regulating, and sometimes preventing, their passage
      to target regions. Routes of entry differ between hydrophobic and hydrophilic
      agents, often with a structure dependency; specialized uptake mechanisms are
      exploited and portage transport can occur for pro-drug antibacterials. Uptake
      isotherms offer insight into the sorption process and can sometimes shed light on
      biocide mechanisms of action. The multi-component barrier system of Gram-negative
      bacteria offers opportunities for phenotypic resistance development where
      partitioning or exclusion minimizes the delivery of an antibacterial agent to the
      target site. Active efflux processes are recognized as increasingly relevant
      mechanisms for resistance, potentially offering routes to biocide:antibiotic
      cross-resistance. These mechanisms may be targeted directly in an attempt to
      compromise their role in microbial survival.

PMID- 12000612
TI  - Cellular impermeability and uptake of biocides and antibiotics in Gram-positive
      bacteria and mycobacteria.
AB  - Gram-positive bacteria possess a permeable cell wall that usually does not
      restrict the penetration of antimicrobials. However, resistance due to restricted
      penetration can occur, as illustrated by vancomycin-intermediate resistant
      Staphylococcus aureus strains (VISA) which produce a markedly thickened cell
      wall. Alterations in these strains include increased amounts of nonamidated
      glutamine residues in the peptidoglycan and it is suggested that the resistance
      mechanism involves 'affinity trapping' of vancomycin in the thickened cell wall.
      VISA strains have reduced doubling times, lower sensitivity to lysostaphin and
      reduced autolytic activity, which may reflect changes in the D-alanyl ester
      content of the wall and membrane teichoic acids. Mycobacterial cell walls have a
      high lipid content, which is assumed to act as a major barrier to the penetration
      of antimicrobial agents. Relatively hydrophobic antibiotics such as rifampicin
      and fluoroquinolones may be able to cross the cell wall by diffusion through the
      hydrophobic bilayer composed of long chain length mycolic acids and glycolipids.
      Hydrophilic antibiotics and nutrients cannot diffuse across this layer and are
      thought to use porin channels which have been reported in many species of
      mycobacteria. The occurrence of porins in a lipid bilayer supports the view that
      the mycobacterial wall has an outer membrane analogous to that of Gram-negative
      bacteria. However, mycobacterial porins are much less abundant than in the Gram
      negative outer membrane and allow only low rates of uptake for small hydrophilic
      nutrients and antibiotics.

PMID- 12000613
TI  - Mechanisms of bacterial biocide and antibiotic resistance.
AB  - Resistance to antibiotics is increasingly commonplace amongst important human
      pathogens. Although the mechanism(s) of resistance vary from agent to agent they
      typically involve one or more of: alteration of the drug target in the bacterial
      cell, enzymatic modification or destruction of the drug itself, or limitation of
      drug accumulation as a result of drug exclusion or active drug efflux. While most
      of these are agent specific, providing resistance to a single antimicrobial or
      class of antimicrobial, there are currently numerous examples of efflux systems
      that accommodate and, thus, provide resistance to a broad range of structurally
      unrelated antimicrobials -- so-called multidrug efflux systems. Resistance to
      biocides is less common and likely reflects the multiplicity of targets within
      the cell as well as the general lack of known detoxifying enzymes. Resistance
      typically results from cellular changes that impact on biocide accumulation,
      including cell envelope changes that limit uptake, or expression of efflux
      mechanisms. Still, target site mutations leading to biocide resistance, though
      rare, are known. Intriguingly, many multidrug efflux systems also accommodate
      biocides (e.g. triclosan) such that strains expressing these are both antibiotic-
      and biocide-resistant. Indeed, concern has been expressed regarding the potential
      for agents such as triclosan to select for strains resistant to multiple
      clinically-relevant antibiotics. Some of the better characterized examples of
      such multidrug efflux systems can be found in the opportunistic pathogen
      Pseudomonas aeruginosa where they play an important role in the noted intrinsic
      and acquired resistance of this organism to antibiotics and triclosan. These
      tripartite pumps include an integral inner membrane drug-proton antiporter, an
      outer membrane- and periplasm-spanning channel-forming protein and a periplasmic
      link protein that joins these two. Expression of efflux genes is governed
      minimally by the product of a linked regulatory gene that is in most cases the
      target for mutation in multidrug resistant strains hyperexpressing these efflux
      systems. Issues for consideration include the natural function of these efflux
      systems and the therapeutic potential of targeting these systems in combating
      acquired multidrug resistance.

PMID- 12000614
TI  - Active efflux, a common mechanism for biocide and antibiotic resistance.
AB  - Energy-driven drug efflux systems are increasingly recognized as mechanisms of
      antibiotic resistance. Chromosomally located or acquired by bacteria, they can
      either be activated by environmental signals or by a mutation in a regulatory
      gene. Two major categories exist: those systems energized by proton motive force
      and those dependent on ATP. The pumps may have limited or broad substrates, the
      so-called multiple drug resistance pumps, which themselves form a number of
      related families. The multiple antibiotic resistance (mar) locus and mar regulon
      in Escherichia coli and other members of the Enterobacteriaceae is a paradigm for
      a generalized response locus leading to increased expression of efflux pumps. One
      such pump, the AcrAB pump extrudes biocides such as triclosan, chlorhexidine and
      quaternary ammonium compounds as well as multiple antibiotics. In Pseudomonas
      aeruginosa, a number of multidrug efflux pumps export a broad range of
      substrates. Since bacteria expressing these pumps thwart the efficacy of both
      kinds of therapeutic agents which control infectious diseases -- biocides which
      prevent transmission of infectious disease agents and antibiotics which treat and
      cure infectious diseases -- they are of particular concern. The prudent use of
      antibiotics and biocides will guard against the selection and propagation of drug
      resistant mutants and preserve the efficacy of these valuable anti-infective
      agents.

PMID- 12000615
TI  - Products containing biocides: perceptions and realities.
AB  - The mechanisms of action for chemical germicides and antibiotics for inactivating
      microorganisms are significantly different and methods for determining resistance
      by microorganisms to these agents are also different. Chemical germicides usually
      have multiple targets and the mechanisms for inactivation and resistance are not
      measured in absolute terms but rather in the rapidity with which they reduce
      levels of microorganisms. The term tolerance is much more suited for germicides
      than the term resistance. The mechanism of resistance to chemical germicides is
      often dependent on the concentration of the germicide. At high concentrations
      multiple cellular and metabolic targets are involved, and at low concentrations
      fewer cellular targets. In contrast antibiotics usually have a singular cellular
      or metabolic target and resistance implies the ability of the microorganism to
      grow in the presence of the antibiotic, and in a clinical sense, to initiate or
      continue infection in the presence of the antibiotic. When methods used to assess
      resistance to antibiotics are applied to chemical germicides, inappropriate
      interpretations can be made regarding the ability of microorganisms to develop
      resistance to antibiotics as a result of developing resistance to chemical
      germicides. The use of chemical germicides in health-care institutions and
      especially the home setting has increased in recent years. Although there may be
      an overuse of germicides in these settings the consequence is a cost issue and
      not one that involves the development of antibiotic resistant microorganisms.

PMID- 12000616
TI  - Antibiotic exposure as a risk factor for emergence of resistance: the influence
      of concentration.
AB  - Evolution of antibiotic resistance (AR) is increasingly perceived as a major
      clinical problem. The use of bactericidal antibiotics may protect against this,
      to some extent, by eradication of the pathogen, but the borders between cidal and
      inhibitory activity in the patient are often blurred. In addition, there are
      clinical reasons why eradication of the pathogen may not always be desirable.
      Antibiotic dosing schedules are currently driven by the perception that T >MIC
      and AUIC are the main predictors of outcome for time-dependent and concentration
      dependent antibiotics, respectively. In the context of protecting against
      development of resistance in the pathogen however, peak antibiotic concentration
      and the concept of mutant prevention concentrations may be more important. The
      role of post-antibiotic and sub-MIC effects is more conjectural. Considerations
      of mechanisms of resistance and their relationship to antibiotic dosing schedules
      will also be highlighted. Lastly, the relevance of all this to the development of
      resistance in the normal bacterial flora will be discussed.

PMID- 12000617
TI  - Antimicrobial resistance and the food chain.
AB  - The extent to which antibiotics given to animals contribute to the overall
      problem of antibiotic resistance in man is still uncertain. The development of
      resistance in some human pathogens, such as methicillin-resistant Staphylococcus
      aureus and multi-drug resistant Mycobacterium tuberculosis, is linked to the use
      of antimicrobials in man and there is no evidence for animal involvement.
      However, there are several good examples of transfer of resistant bacteria or
      bacterial resistance genes from animals to man via the food chain. A bacterial
      ecosystem exists with simple and complex routes of transfer of resistance genes
      between the bacterial populations; in addition to transfer of organisms from
      animals to man, there is also evidence of resistance genes spilling back from
      humans into the animal population. This is important because of the amplification
      that can occur in animal populations. The most important factor in the selection
      of resistant bacteria is generally agreed to be usage of antimicrobial agents and
      in general, there is a close association between the quantities of antimicrobials
      used and the rate of development of resistance. The use of antimicrobials is not
      restricted to animal husbandry but also occurs in horticulture (for example,
      aminoglycosides in apple growing) and in some other industrial processes such as
      oil production.

PMID- 12000618
TI  - Clinical significance of the emergence of bacterial resistance in the hospital
      environment.
AB  - Antibiotic resistance is an increasing threat in hospitals and both morbidity and
      mortality from infections are greater when caused by drug-resistant organisms.
      Whilst hospitals are universally blamed for this increase, there is an
      insufficient appreciation of external sources of resistance, such as when
      patients are admitted to hospitals from long-term care facilities in the
      community. The use of antibiotics in family practice and animal husbandry has
      also been linked to drug resistance being encountered in the hospital setting.
      Justifiable hospital antibiotic use, which can be life saving, may lead to
      'collateral damage' with the emergence of resistance in non-target bacteria in
      the bowel, for example, with subsequent spread by cross-infection. At a
      management level, antibiotic resistance can have a significant impact on the
      ability of hospitals to maintain services since cohorting of patients and ward
      closures from outbreaks add to continuing bed shortages and waiting lists.
      Hospital laboratories must review their standard operating procedures since some
      resistance mechanisms may be missed by current methods of antibiotic
      susceptibility testing. With increasing public concern from press reports of
      'multiresistant Staphylococcus aureus killer virus' and other drug-resistant
      organisms, there will inevitably be a push by national authorities for more
      surveillance data on antibiotic resistance; however, the cost-effectiveness of
      different surveillance strategies should be considered. Clinical governance and
      risk management are dominant themes in the National Health Service and hospital
      hygiene and antibiotic resistance are likely to feature prominently in audits
      related to these themes in the near future.

PMID- 12000619
TI  - Biofilms in vitro and in vivo: do singular mechanisms imply cross-resistance?
AB  - Microbial biofilm has become inexorably linked with man's failure to control them
      by antibiotic and biocide regimes that are effective against suspended bacteria.
      This failure relates to a localized concentration of biofilm bacteria, and their
      extracellular products (exopolymers and extracellular enzymes), that moderates
      the access of the treatment agent and starves the more deeply placed cells.
      Biofilms, therefore, typically present gradients of physiology and concentration
      for the imposed treatment agent, which enables the less susceptible clones to
      survive. Such clones might include efflux mutants in addition to genotypes with
      modifications in single gene products. Clonal expansion following subeffective
      treatment would, in the case of many antibiotics, lead to the emergence of a
      resistant population. This tends not to occur for biocidal treatments where the
      active agent exhibits multiple pharmacological activity towards a number of
      specific cellular targets. Whilst resistance development towards biocidal agents
      is highly unlikely, subeffective exposure will lead to the selection of less
      susceptible clones, modified either in efflux or in their most susceptible
      target. The latter might also confer resistance to antibiotics where the target
      is shared. Thus, recent reports have demonstrated that sublethal concentrations
      of the antibacterial and antifungal agent triclosan can select for resistant
      mutants in Escherichia coli and that this agent specifically targets the enzyme
      enoyl reductase that is involved in lipid biosynthesis. Triclosan may, therefore,
      select for mutants in a target that is shared with the anti-E. coli diazaborine
      compounds and the antituberculosis drug isoniazid. Although triclosan may be a
      uniquely specific biocide, sublethal concentrations of less specific
      antimicrobial agents may also select for mutations within their most sensitive
      targets, some of which might be common to therapeutic agents. Sublethal treatment
      with chemical antimicrobial agents has also been demonstrated to induce the
      expression of multidrug efflux pumps and efflux mutants. Whilst efflux does not
      confer protection against use concentrations of biocidal products it is
      sufficient to confer protection against therapeutic doses of many antibiotics. It
      has, therefore, been widely speculated that biocide misuse may have an insidious
      effect, contributing to the evolution and persistence of drug resistance within
      microbial communities. Whilst such notions are supported by laboratory studies
      that utilize pure cultures, recent evidence has strongly refuted such linkage
      within the general environment where complex, multispecies biofilms predominate
      and where biocidal products are routinely deployed. In such situations the
      competition, for nutrients and space, between community members of disparate
      sensitivities far outweighs any potential benefits bestowed by the changes in an
      individual's antimicrobial susceptibility.

PMID- 12000620
TI  - Biocide use in the food industry and the disinfectant resistance of persistent
      strains of Listeria monocytogenes and Escherichia coli.
AB  - AIMS: The aims of the project were threefold: to survey the use of disinfectants
      in the UK food industry; to assess the product and environmental microflora of
      selected food factories for the persistence of Listeria monocytogenes and
      Escherichia coli; and to determine the disinfectant resistance of any persistent
      strains. METHODS AND RESULTS: A survey of the use of disinfectants in the UK food
      industry was undertaken in which a total of 40 sites were visited and a further
      77 postal questionnaires were returned from farms, food manufacture, food
      transport and food retail sites. Quaternary ammonium compounds (QACs) were
      predominantly used, applied in small volumes as a mist. Approximately 30,000
      samples from the product and environment of five chilled food factories were
      examined for L. monocytogenes and E. coli over a 3 year period. A total of 181 L.
      monocytogenes and 176 E. coli isolates were ribotyped to yield 19 and 34
      ribogroups, respectively. Some strains were isolated only from the product, a
      number only from the environment and others from both niches. Some strains were
      seen to be persistent for the duration of the sampling exercise (2-3 years). The
      most common L. monocytogenes and E. coli strains, together with two environmental
      L. monocytogenes strains, were assessed for any resistance to commercial
      disinfectants as compared with a laboratory L. monocytogenes disinfectant testing
      strain. The resistance of the L. monocytogenes and E. coli strains isolated from
      the factory were not significantly different from the laboratory control strain.
      CONCLUSIONS: Persistent strains of L. monocytogenes and E. coli are found in the
      UK food industry, though this persistence is not related to their increased
      susceptibility to the most commonly used disinfectants. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The concept of a persistent microflora in food factories will have
      an impact on the future selection of suitable control options, including the use
      of biocides.

PMID- 12000621
TI  - Introduction of biocides into clinical practice and the impact on antibiotic
      resistant bacteria.
AB  - Biocides and other antimicrobial agents have been employed for centuries. Much
      later, iodine found use as a wound disinfectant, chlorine water in obstetrics,
      alcohol as a hand disinfectant and phenol as a wound dressing and in antiseptic
      surgery. In the early part of the twentieth century, other chlorine-releasing
      agents (CRAs), and acridine and other dyes were introduced, as were some
      quaternary ammonium compounds (QACs, although these were only used as biocides
      from the 1930s). Later still, various phenolics and alcohols, formaldehyde and
      hydrogen peroxide were introduced and subsequently (although some had actually
      been produced at an earlier date) biguanides, iodophors, bisphenols, aldehydes,
      diamidines, isocyanurates, isothiazolones and peracetic acid. Antibiotics were
      introduced clinically in the 1940s, although sulphonamides had been synthesized
      and used previously. After penicillin came streptomycin and other aminoglycosides
      aminocyclitols, tetracyclines, chloramphenicol, macrolides, semi-synthetic beta
      lactams, glycopeptides, lincosamides, 4-quinolones and diaminopyrimidines.
      Bacterial resistance to antibiotics is causing great concern. Mechanisms of such
      resistance include cell impermeability, target site mutation, drug inactivation
      and drug efflux. Bacterial resistance to biocides was described in the 1950s and
      1960s and is also apparently increasing. Of the biocides listed above, cationic
      agents (QACs, chlorhexidine, diamidines, acridines) and triclosan have been
      implicated as possible causes for the selection and persistence of bacterial
      strains with low-level antibiotic resistance. It has been claimed that the
      chronological emergence of qacA and qacB determinants in clinical isolates of
      Staphylococcus aureus mirrors the introduction and usage of cationic biocides.

PMID- 12000622
TI  - Quantitative assessment of risk reduction from hand washing with antibacterial
      soaps.
AB  - The Centers for Disease Control and Prevention have estimated that there are
      3,713,000 cases of infectious disease associated with day care facilities each
      year. The objective of this study was to examine the risk reduction achieved from
      using different soap formulations after diaper changing using a microbial
      quantitative risk assessment approach. To achieve this, a probability of
      infection model and an exposure assessment based on micro-organism transfer were
      used to evaluate the efficacy of different soap formulations in reducing the
      probability of disease following hand contact with an enteric pathogen. Based on
      this model, it was determined that the probability of infection ranged from
      24/100 to 91/100 for those changing diapers of babies with symptomatic
      shigellosis who used a control product (soap without an antibacterial
      ingredient), 22/100 to 91/100 for those who used an antibacterial soap
      (chlorohexadine 4%), and 15/100 to 90/100 for those who used a triclosan (1.5%)
      antibacterial soap. Those with asymptomatic shigellosis who used a non
      antibacterial control soap had a risk between 49/100,000 and 53/100, those who
      used the 4% chlorohexadine-containing soap had a risk between 43/100,000 and
      51/100, and for those who used a 1.5% triclosan soap had a risk between
      21/100,000 and 43/100. The adequate washing of hands after diapering reduces risk
      and can be further reduced by a factor of 20% by the use of an antibacterial
      soap. Quantitative risk assessment is a valuable tool in the evaluation of
      household sanitizing agents and low risk outcomes.

PMID- 12000623
TI  - Significance of biocide usage and antimicrobial resistance in domiciliary
      environments.
AB  - Recent events have raised awareness of the need for effective hygiene in the
      home. Not least is the requirement to reduce antibiotic resistance by reducing
      the need for antibiotic prescribing. Current evidence suggests that improved
      hygiene in the domestic setting could have a significant impact. Recently, it has
      been suggested that widespread biocide usage, particularly in consumer products,
      may be a contributory factor in antibiotic resistance. In developing home hygiene
      policies, however, it is important that biocide use as an integral part of good
      hygiene practice is not discouraged in situations where there is real benefit.
      Although laboratory data indicate possible links, it is necessary to assess
      whether and to what extent biocide exposure could contribute to antibiotic
      resistance in clinical practice. The extent to which reduced susceptibility to
      biocides resulting from biocide exposure could compromise their 'in-use'
      effectiveness must also be considered. Equally, it is important that changes in
      susceptibility induced by biocide exposure are assessed relative to those induced
      by antibiotic exposure or the phenotypic changes induced by 'normal'
      environmental 'stresses'. It is proposed that to be effective, home hygiene
      policy should be based on the concept of risk assessment and risk prevention.
      Using this approach, critical risk situations are identified and appropriate
      hygiene procedures applied to reduce risks. This may involve either soap and
      water cleaning, or cleaning combined with a disinfection process. A 'targeted'
      hygiene approach not only provides the most effective means of preventing
      infectious disease, it also offers a means of addressing concerns about 'too much
      hygiene' and 'too many antibacterials' amongst a public who have lost confidence
      regarding appropriate hygiene for their home environment.

PMID- 12000624
TI  - Susceptibility of antibiotic-resistant cocci to biocides.
AB  - Biocide resistance has hitherto been a poorly studied subject, possibly due to
      the belief that such resistance was rare and clinically insignificant. Various
      recent findings, however, have underlined the importance of biocide resistance as
      a clinically relevant phenomenon. Outbreaks of biocide-resistant organisms in
      hospitals have been described and the genetic mechanism for resistance to
      quaternary ammonium compounds (QACs) in Staphylococcus aureus has now been
      elucidated. Mycobacteria resistant to commonly used endoscope disinfectants are
      now commonly reported and have caused numerous adverse clinical events. Cross
      resistance between triclosan and antituberculous drugs has been demonstrated in
      other strains of mycobacteria. This is related to a common mechanism of action.
      The work presented here describes studies into the biocide resistance of
      antibiotic-resistant cocci and attempts to create biocide-resistant strains in
      vitro. Strains of staphylococci (including methicillin-resistant Staph. aureus
      (MRSA)) and enterococci (including vancomycin-resistant enterococci (VRE)) had
      their susceptibility to biocides assayed using broth macro dilution methods and
      resistant strains were selected by serial subculture on biocide-containing media.
      Mutants were created with relative ease; for instance, triclosan minimal
      bactericidal concentrations (MBCs) increased from 0.002 to 3.12 mg l(-1). Some
      strains of MRSA which have intermediate resistance to glycopeptides were
      demonstrated to have decreased susceptibility to some biocides. Biocide
      resistance amongst enterococci was demonstrated although there was no clear
      correlation between biocide and antibiotic resistance. The exact mechanisms of
      resistance in these strains are still being studied but it is clear that biocide
      resistance is an important clinical phenomenon.

PMID- 12000625
TI  - Susceptibility of antibiotic-resistant Gram-negative bacteria to biocides: a
      perspective from the study of catheter biofilms.
AB  - Bacteria resistant to both the agents deployed to prevent infections and those
      used to treat infections would be formidable nosocomial pathogens. The aim of
      this paper is to review the evidence that Gram-negative bacteria resistant to
      antibiotics and biocides have emerged and been responsible for catheter
      associated urinary tract infection. A study of patients undergoing intermittent
      bladder catheterization revealed that the frequent application of the antiseptic
      chlorhexidine to the perineal skin prior to the insertion of the catheter was
      effective against the normal Gram-positive skin flora but not against the Gram
      negative organisms that subsequently colonized this site. Organisms such as
      Providencia stuartii, Pseudomonas aeruginosa and Proteus mirabilis were
      repeatedly isolated from the skin of these patients and inevitably went on to
      cause urinary infections. The minimum inhibitory concentration (MIC) of
      chlorhexidine for many of these strains proved to be 200-800 microg ml(-1)
      compared with the 10-50 microg ml(-1) recorded for reference strains of Gram
      negative species. A subsequent survey of over 800 Gram-negative isolates from
      urinary tract infections in patients from both hospitals and the community
      revealed that chlorhexidine resistance was not a widespread phenomenon, but was
      restricted to these species and to units where the care of catheterized patients
      involved the extensive use of chlorhexidine. Analysis of the antibiotic
      resistance patterns revealed that the chlorhexidine-resistant strains were also
      multidrug resistant. Other clinical studies also reported catheter-associated
      infections with chlorhexidine- and multidrug-resistant strains of Pr. mirabilis
      when chlorhexidine was being used extensively. This species poses particular
      problems to the catheterized patient. Chlorhexidine thus proved counterproductive
      in the care of catheters and its use in this context has been largely abandoned.
      Suggestions of reintroducing this agent in the form of biocide-impregnated
      catheters should be resisted.

PMID- 12000626
TI  - Antibiotic and biocide resistance in bacteria: comments and conclusions.

PMID- 12000629
TI  - Nursing in theory and in practice.

PMID- 12000630
TI  - Nurses' knowledge of error in blood pressure measurement technique.
AB  - Errors in measuring blood pressure may have significant impact on the
      investigation and treatment of patients. Errors arise from faults in measurement
      technique or the equipment used. In Australia, blood pressure measurement
      technique is taught to nurses during their undergraduate education and may not be
      reviewed again. This observational, descriptive study surveyed clinical nurses at
      a metropolitan teaching hospital at shift hand-over time. Participation was
      voluntary and anonymous by 78 nurses who answered a questionnaire to determine
      the need and focus for updating blood pressure measurement technique. Sixty-one
      per cent of participants conformed to currently accepted practice in identifying
      systolic blood pressure, and 71% diastolic blood pressure; 54% correctly
      interpreted a description of blood pressure sounds containing an auscultatory
      gap. Correct answers for assessment of faulty equipment were given by 58%,
      assessing cuff size by 57%, arm position for seated measurement by 14%,
      determination of inflation pressure by 29% and deflation rate 62%. Incidence of
      terminal digit preference was 32%. These findings indicate that knowledge of
      participants was inadequate to perform blood pressure measurement in a
      standardized manner, and prevent introduced error.

PMID- 12000631
TI  - Comprehensive measurement of maternal satisfaction: the modified Mason Survey.
AB  - A three-stage process was undertaken to identify and modify a tool that was
      capable of measuring the many aspects of maternal satisfaction relevant to
      Australian women. First, the scope of maternal satisfaction to be measured was
      defined by summarizing available literature and surveys purporting to measure
      maternal satisfaction (including surveys used in maternity services in New South
      Wales). The multidimensional nature of maternal satisfaction was confirmed, with
      16 core aspects (common to the literature and local surveys) and nine additional
      unique aspects of maternal satisfaction being identified. Second, these core and
      additional aspects were used to examine the comprehensiveness of the Mason
      Survey, a survey recommended by the National Health and Medical Research Council
      of Australia for use in maternity services. Eighty-eight per cent of the core and
      additional aspects (22/25) were found to be present in the Mason Survey. Third,
      an expert panel further modified the Mason Survey by removing items not
      applicable to the Australian context. The modified Mason Survey is a
      comprehensive measure of maternal satisfaction suitable for Australian women and
      capable of providing valuable information on the quality of services and future
      planning for maternity services.

PMID- 12000632
TI  - Adolescent coping with grief after the death of a loved one.
AB  - The purpose of this article was to describe adolescent coping after the death of
      a loved one. Data were obtained by two self-report questionnaires filled in by 14
      16-year-old pupils in two secondary schools in Finland. The sample consisted of
      89 adolescents (70% girls) who had each experienced the death of a loved one. The
      instrument used in the study was developed by Hogan and DeSantis. The article
      reports the responses to two open-ended questions. The data were analyzed using
      content analysis. The most important factors that helped adolescents cope with
      grief were self-help and support from parents, relatives and friends. However,
      the official social support system was not experienced as very helpful. No one
      reported help, for example, from school health services. According to the
      adolescents, fear of death, a sense of loneliness and intrusive thoughts were
      factors that hindered coping with grief. Some respondents felt that parents or
      friends were an additional burden on them. The results are discussed in terms of
      identifying the different impact of social support, the importance of self-help
      and professional help. Knowledge of factors that have an effect on adolescent
      coping with bereavement is important for families, effective nursing practice,
      school health services and parents.

PMID- 12000633
TI  - Nurses' and patients' perceptions of dignity.
AB  - It is generally agreed in the nursing literature that the maintenance of patient
      dignity is an important element of nursing care that is highly valued by
      patients. Despite this, dignity is seldom defined and there are few guidelines
      that nurses may use in their practice to safeguard individual patients' dignity.
      This phenomenological study aimed to uncover patients' and nurses' perceptions of
      dignity, formulate a definition of dignity based on the experience of patients
      and nurses, and identify nursing practices that maintain or compromise patient
      dignity. The study found that the characteristics nurses associated with dignity
      were many and varied. Important elements in the meaning the nurses ascribed to
      the notion of patient dignity were the elements of respect, privacy, control,
      advocacy and time. The themes which emerged from the patient interviews were
      similar to those which emerged from the interviews with nurses. The
      characteristics that patients attributed to dignity and its maintenance included
      respect, privacy, control, choice, humour and matter-of-factness.

PMID- 12000634
TI  - How does an implantable cardioverter defibrillator (ICD) affect the lives of
      patients and their families?
AB  - This study aimed to identify the lived experience of patients with implantable
      cardioverter defibrillators (ICD) and their families. The methodology used was
      interpretative phenomenology. Unstructured interviews were conducted with three
      family members and three ICD recipients. Using a methodological approach outlined
      by van Manen, the participants transcribed texts were analysed looking for
      similar concepts and ideas that developed into themes that explicated the meaning
      of this phenomena. The themes that emerged were: dependence, which encompassed
      their perceptions about the life-saving device; the memory of their first
      defibrillation experience; lifestyle changes, which incorporated modification
      techniques; lack of control, which highlighted feelings such as fear, anxiety and
      powerlessness; mind game, which illustrated psychological challenges; and the
      issue of security, demonstrating how 'being there' and not 'being there' impacted
      on their everyday lives. The long-term outcomes of living with an ICD are
      important considerations for all health-care providers. This research highlights
      the everyday activities of recipients, the lifestyle changes they have made, the
      emotional significance of the device and the psychological coping strategies that
      the participants have adopted. The findings of this research will allow health
      care professionals to be better prepared to provide education and support for ICD
      recipients and their families in regards to issues related to insertion of the
      device during the postinsertion recovery period and for long-term management
      after hospital discharge.

PMID- 12000635
TI  - Children's needs during hospitalization: an observational study of hospitalized
      boys.
AB  - Twenty-one boys (age range 5 months to 16 years) were followed during their stay
      at hospital. Total observation time was 120 h. Field notes were made immediately
      after each observation. These were then transcribed into a narrative text, which
      was analysed by content analysis. Six categories of needs were identified during
      non-threatening situations at the hospital: the need for activity, the need for
      new experiences, the need for information, the need for participation, the need
      for praise and recognition, and needs related to physical resources. Four
      categories of needs were found during episodes of threat, discomfort and pain:
      the need for control, the need for having their parents nearby, the need for what
      is familiar, and the need for integrity. These results indicate that those
      involved in the care of children should be alert to the fact that as
      circumstances change, different needs have to be met. During non-threatening
      situations efforts should be made to inform children and to allow them to
      continue with their everyday lives. During threatening situations the children
      should be assisted and supported in keeping the situation under control.

PMID- 12000636
TI  - Family caregiving of the elderly and Long-Term Care Insurance in rural Japan.
AB  - In this study, data were used from a qualitative research study and a literature
      review to present the characteristics of family caregiving for the elderly in
      rural Japan, and changes and issues related to home care since the recent
      implementation of Long-Term Care Insurance (LTCI) for the Elderly. The results of
      a quantitative study are also used to describe the perceptions of public health
      nurses about their role in the LTCI, and the future role of Japanese nurses in
      rural Japan is discussed.

PMID- 12000637
TI  - Hiring foreign nurses in the USA.

PMID- 12000638
TI  - Association of midgut defensin with a novel serine protease in the blood-sucking
      fly Stomoxys calcitrans.
AB  - Using ELISA we provide direct evidence that the midgut defensins of the blood
      sucking fly Stomoxys calcitrans are secreted into the gut lumen. We show that
      midgut defensin peptide levels increase up to fortyfold in response to a blood
      meal but not to a sugar meal. The data suggests the midgut defensin genes are
      post-transcriptionally regulated and that their function is protection of the
      stored blood meal from bacterial attack while it awaits digestion. Using
      recombinant defensins produced in Pichia pastoris we demonstrate that while in
      the gut cells the midgut defensins are bound in an SDS-stable complex to proteins
      with an apparent molecular weight of > 26 kDa from which they are released when
      secreted into the gut lumen. This > 26 kDa protein (Ssp3) has been cloned and
      sequenced and is a member of the serine protease S1 family with homologies to
      multiple insect proteases and to vertebrate trypsins and elastases.

PMID- 12000639
TI  - Glucosamine:fructose-6-phosphate aminotransferase: gene characterization, chitin
      biosynthesis and peritrophic matrix formation in Aedes aegypti.
AB  - Glucosamine:fructose-6-phosphate aminotransferase (GFAT) catalyses the formation
      of glucosamine 6-phosphate and is the first and rate-limiting enzyme of the
      hexosamine biosynthetic pathway. The final product of the hexosamine pathway, UDP
      N-acetyl glucosamine, is an active precursor of numerous macromolecules
      containing amino sugars, including chitin in fungi and arthropods. Chitin is one
      of the essential components of insect cuticle and peritrophic matrix. The
      peritrophic matrix is produced in the midgut of mosquitoes in response to
      bloodfeeding, and may affect vector competence by serving as a physical barrier
      to pathogens. It is hypothesized that GFAT plays a regulatory role in
      biosynthesis of chitin and peritrophic matrix formation in insects. We cloned and
      sequenced the GFAT gene (AeGfat-1) and its 5' regulatory region from Aedes
      aegypti. There is no intron in AeGfat-1 and there are two potential transcription
      start sites. AeGfat-1 cDNA is 3.4 kb in length and its putative translation
      product is 75.4 kDa. The amino acid sequence of GFAT is highly conserved in lower
      and higher eukaryotes, as well as in bacteria. AeGfat-1 message is constitutively
      expressed but is gradually up-regulated in the midgut after bloodfeeding. The
      putative regulatory region of the gene contains the ecdysone response element,
      E74, and Broad complex motifs, similar to what is found in the glutamine
      synthetase gene in Ae. aegypti. Results suggest that Ae. aegypti GFAT-1 may have
      a regulatory role in chitin biosynthesis and peritrophic matrix formation, and
      probably is under the regulation of ecdysteroids.

PMID- 12000640
TI  - Induction of the white egg 3 mutant phenotype by injection of the double-stranded
      RNA of the silkworm white gene.
AB  - Injection of double-stranded RNA (dsRNA) corresponding to the silkworm white gene
      (Bmwh3) into preblastoderm eggs of the wild-type silkworm induced phenotypes
      similar to those observed with mutants of the white egg 3 locus (10-19.6). The
      induced phenotypes were characterized by the presence of white eggs and
      translucent larval skin. Northern analysis showed that the expression of the
      endogenous Bmwh3 gene in the injected embryos was distinctly depressed.
      Furthermore, the injection of the GFP dsRNA inhibited the expression of the GFP
      gene from a plasmid co-injected with the dsRNA but did not depress the expression
      of the Bmwh3 gene. These findings demonstrate that sequence-specific RNA
      interference occurred in the silkworm. We conclude from the results that the RNA
      interference can be applied as a tool for the analysis of the gene function in
      the lepidopteran insects.

PMID- 12000641
TI  - Expression of D7 and D7-related proteins in the salivary glands of the human
      malaria mosquito Anopheles stephensi.
AB  - Full-length cDNA clones encoding D7 (AnsD7) and D7-related (AnsD7r1) secreted
      salivary gland proteins were isolated from Anopheles stephensi. Corresponding
      proteins were separated by SDS-PAGE and analysed by N-terminal sequencing, which
      also identified a second D7-related protein (AnsD7r2). AnsD7 encodes a protein of
      37 kDa, AnsD7r1 of 18 kDa, and AnsD7r2 of 16 kDa. Polyclonal antibodies against
      recombinant AnsD7 showed immunological cross-reactivity with the D7-related
      proteins, and alignment demonstrated sequence similarity between the C-terminal
      region of AnsD7 and the D7-related proteins. AnsD7, AnsD7r1 and AnsD7r2 were
      major female-specific salivary gland proteins, and Western blotting,
      immunohistochemistry and immunogold labelling demonstrated expression was
      predominantly in the secretory cavities of the distal-lateral and median lobes.
      Expression and localization of D7 and D7-related proteins was similar in
      Plasmodium berghei-infected and uninfected mosquitoes.

PMID- 12000642
TI  - Sequence analysis and expression of a virus-like particle protein, VLP2, from the
      parasitic wasp Venturia canescens.
AB  - Endoparasitoid wasps produce maternal protein secretions, which are transported
      into the body of insect hosts at oviposition to regulate host physiology for
      successful development of their offspring. Venturia canescens calyx fluid
      contains so-called virus-like particles (VLPs) that are essential for immune
      evasion of the developing parasitoid inside the host. VLPs consist of four major
      proteins. In this paper, we describe the isolation and molecular cloning of a
      gene (vlp2) that is a constituent of VLPs and discuss its possible role in VLP
      structure and function.

PMID- 12000643
TI  - The involvement of ovarian tumour in the intracellular localization of Sex-lethal
      protein.
AB  - The Drosophila ovarian tumour gene is required at multiple times in the germline
      for oogenesis. A second gene, Sex-lethal, controls sex determination in the soma
      and also has a separate germline function affecting similar oogenic stages as
      ovarian tumour. We demonstrate that ovarian tumour is not required for early Sex
      lethal gene expression in the female germline, as had been previously reported.
      Instead, we provide evidence that ovarian tumour has a specific role in the
      developmentally regulated accumulation of SEX-LETHAL protein within the cytoplasm
      and nucleus. Furthermore, the examination of nurse cell polytene chromosomes
      produced by certain ovarian tumour mutations showed that SEX-LETHAL protein can
      associate with discrete chromosomal sites in the germline and that this pattern
      appears to change as the egg chamber matures. This is the first indication that
      SEX-LETHAL is capable of direct physical interactions with chromosomes (albeit in
      a mutant background) and is consistent with the developmentally regulated nuclear
      localization of SEX-LETHAL being important for oogenesis.

PMID- 12000644
TI  - cDNA cloning of two different serine protease inhibitor precursors in the
      migratory locust, Locusta migratoria.
AB  - Recently, a novel serine protease-inhibiting peptide family, designated as the
      'pacifastin family', has been described in locusts and crayfish. All members of
      this family possess a characteristic cysteine-rich domain. The present study
      describes the cDNA cloning, sequencing and transcript distribution of two novel
      pacifastin-related peptide precursors in the migratory locust, Locusta
      migratoria. Only one of the encoded peptides (HI) was identified previously,
      whereas six others represent new members of the pacifastin family. Northern blot
      analysis showed that both precursor transcripts are present in adult locust fat
      body. These could not be detected in the midgut. Interestingly, an in silico data
      mining approach of the expressed sequence tags (EST) database revealed the
      existence of Manduca sexta and Bombyx mori cDNAs that display pronounced sequence
      similarities with these locust pacifastin-related transcripts.

PMID- 12000645
TI  - cDNA cloning, characterization and gene expression of nitric oxide synthase from
      the silkworm, Bombyx mori.
AB  - Molecular cloning and nucleotide sequencing of cDNA encoding Bombyx mori nitric
      oxide synthase (BmNOS) was conducted to analyse its possible role in insect
      immunity. The amino acid sequence deduced from the BmNOS cDNA showed 84%, 54% and
      53% identity with those of NOSs from Manduca sexta, Drosophila melanogaster and
      Rhodonius prolixus. Recombinant BmNOS produced in insect cells using baculovirus
      was found to require NADPH, Ca2+, calmodulin and tetrahydrobiopterin (BH4) for
      its activity. The BmNOS gene was constitutively expressed at a low level in the
      larval fat body, haemocyte, Malpighian tubule and midgut, and adult antenna, and
      induced strongly in the fat body by lipopolysaccharide (LPS), suggesting that the
      BmNOS gene plays different physiological roles in different tissues. Injection of
      NO donors that produce NO in vivo induced the gene expression of an antibacterial
      peptide, cecropin B, strongly suggesting that NO produced by BmNOS following LPS
      stimulation is involved in signal transduction as a signalling molecule for
      immune gene expression.

PMID- 12000646
TI  - Hemolin gene silencing by ds-RNA injected into Cecropia pupae is lethal to next
      generation embryos.
AB  - There is increasing evidence of an intimate connection between participants in
      the innate immune system and in development. Molecules involved in the
      determination of dorso-ventral polarity in Drosophila have related counterparts
      in the signalling pathways for immune gene activation in both insects and
      mammals. Hemolin from the Giant silkmoth, Hyalophora cecropia, identified as a
      bacteria-inducible molecule and a member of the immunoglobulin superfamily, is
      present as protein and transcripts in oocytes and embryos. We used RNA
      interference (RNAi) to investigate H. cecropia gene function in vivo and
      demonstrated that Hemolin is crucial for the normal development of embryos. When
      RNAi-females were mated, no larvae emerged from their eggs and when dissected,
      the eggs revealed malformed embryos. Western blot analysis confirmed the lack of
      Hemolin gene products. We conclude that Hemolin is necessary for development,
      since the silencing of Hemolin gene expression leads to embryonic lethality.

PMID- 12000647
TI  - cDNA cloning of biotransformation enzymes belonging to the cytochrome P450 family
      in the antennae of the noctuid moth Mamestra brassicae.
AB  - The involvement of cytochrome P450 enzymes in olfaction was demonstrated in
      vertebrates some time ago. In insects these enzymes are well known for their role
      in insecticide resistance, but the involvement of P450 in pheromone degradation
      was only recently demonstrated. Using a PCR strategy, we have isolated two cDNAs
      from the antennae of the cabbage armyworm Mamestra brassicae - CYP4L4 and CYP4S4 
      which encode microsomal P450s. CYP4S4 expression is restricted to the antennae,
      whereas CYP4L4 is also found in the proboscis and legs. Moreover, the two genes
      are strongly expressed in one type of sensory unit of the antennae - the sensilla
      trichodea - which are tuned to the detection of odourants. The putative function
      of the corresponding enzymes is discussed with regard to their respective
      expression patterns.

PMID- 12000648
TI  - Where is health?

PMID- 12000649
TI  - Genetic diversity of Plasmodium falciparum: asexual stages.

PMID- 12000650
TI  - Free bednets to pregnant women through antenatal clinics in Kenya: a cheap,
      simple and equitable approach to delivery.
AB  - Kenya's National Malaria Strategy states that insecticide-treated nets (ITNs)
      would be considered as a free service to pregnant women assuming sufficient
      financial commitment from donors. In 2001, United Nation's Children's Fund
      (UNICEF) and the Government of Kenya brokered support to procure and distribute
      nets and K-O TABs (deltamethrin) to 70 000 pregnant women in 35 districts
      throughout Kenya around Africa Malaria Day. This intervention represented the
      single largest operational distribution of ITN services in Kenya to date, and
      this study evaluates its success, limitations and costs. The tracking process
      from the central level through to antenatal clinic (ANC) facilities suggests that
      of the 70 000 nets procured, 37 206 nets (53%) had been distributed to pregnant
      women throughout the country within 12 weeks. One-fifth of the nets procured (14
      117) had gone out to individuals other than pregnant women, most of these at the
      request of the district teams, with only 2870 nets estimated to have gone astray
      at the ANC facilities. At 12 weeks, the remaining 18 677 nets were still in
      storage awaiting distribution, with more than two-thirds having reached the
      district, and nearly half already being held at ANC facilities. The cost of
      getting a net and K-O TAB to an ANC facility ready for distribution to a pregnant
      woman was US$ 3.81. Accounting for the 14 117 nets that had gone to other users,
      the cost for an ITN received by a pregnant woman was US$ 5.26. Delivering ITNs
      free to pregnant women through ANCs uses an existing system (with positive spin
      offs of low delivery cost and simple logistics), is equitable (as it not only
      targets those who can afford it) and can have the added benefits of strengthening
      ANC service, delivery and use.

PMID- 12000651
TI  - Molecular epidemiology of Plasmodium falciparum infections among asymptomatic
      inhabitants of a holoendemic malarious area in northern Ghana.
AB  - Age dependence of malaria infection was assessed in an age-stratified cluster
      sample of 308 individuals from Kassena-Nankana District of northern Ghana during
      June and July 2000. Overall prevalence of Plasmodium falciparum by microscopy was
      70%, with the maximum among 5-9 year olds. Parasite density was highest
      (geometric mean 1922/microl blood) in 1-2 year olds. Eighty-two per cent of
      samples were positive by polymerase chain reaction (PCR), and restriction
      fragment length polymorphism typing of the P. falciparum msp2 revealed a mean
      msp2 multiplicity of 3.4 (range: 1-8) genotypes per PCR positive sample.
      Multiplicity increased with age until 5-9 years and then started to reduce again
      into adulthood. About 49.3% of infections belonged to the msp2 FC27 allelic
      family and 50.7% to the 3D7 family. On the day of the survey, only 3.6% of the
      participants had fever (axillary temperature >or= 37.5 degrees C) and 2.3% had
      fever associated with parasitaemia. The correlation between parasite density and
      msp2 multiplicity was 0.42; highest among infants, and decreased with age to a
      minimum among 5-9 year olds. Contrasting with results from Tanzania, this
      correlation increased with age in adolescents and adults. Parasite multiplicity
      is very high in this community, and the patterns of age dependence are similar to
      those in other holoendemic sites in Africa, validating the use of the age
      multiplicity relationship as an indicator of malaria endemicity.

PMID- 12000652
TI  - Host age and time of exposure in Trypanosoma brucei gambiense Human African
      Trypanosomiasis.
AB  - Human African Trypanosomiasis is related to behavioural risk factors but complex
      interactions exist between (i) environmental and behavioural risk factors, (ii)
      vector and (iii) human host. Our aim was to investigate the interrelationships
      between previously analysed risk factors and the roles of age and time of
      exposure according to ethnic group and migration status. However, this
      descriptive and retrospective study is based on cases only (no controls) and our
      results must therefore be regarded as hypothesis-generating. Individuals
      originating from areas where sleeping sickness is absent and who settle in an
      endemic area seem to develop the disease after a shorter time of exposure than
      native subjects from endemic areas. Our results emphasise the complexity of
      vector-transmitted disease epidemiology, involving behavioural and/or
      environmental risk factors on the one hand, and more individual ones such as
      ageing, immunity and genetic background on the other hand.

PMID- 12000653
TI  - The use of the paediatric tuberculosis score chart in an HIV-endemic area.
AB  - BACKGROUND: Diagnosing tuberculosis (TB) in a human immunodeficiency virus (HIV)
      endemic area is extremely difficult, as the clinical symptoms of HIV-seropositive
      children can be easily confounded with TB. The paediatric tuberculosis score
      chart (TSC) was developed for resource-poor countries and its use continues to be
      promoted despite the fact that this scoring system has not been evaluated in
      countries with a high HIV prevalence. OBJECTIVE: To assess the utility of the TSC
      in an HIV-endemic area. METHOD: A prospective cohort study conducted between
      January and December 1999 at St Theresa's Mission Hospital, Copperbelt Province,
      Zambia. Results of the TSC (TB score) were compared with the results of a
      diagnostic algorithm, incorporating sputum smear microscopy, culture and
      polymerase chain reaction of Mycobacterium tuberculosis, tuberculin skin test,
      chest X-ray and histology eventually. RESULTS: A total of 147 children were
      enrolled in the study. On the basis of HIV-serology and clinical findings they
      were divided into four groups: children with TB (23 HIV-seropositive; 52 HIV
      seronegative), 21 HIV-infected children without TB and 51 HIV-seronegative
      children without TB. The differences in TB scores between the groups were not
      significant. The sensitivity of the TSC to diagnose TB in this study was 88%; but
      the specificity was only 25%. CONCLUSION: The TSC should not be used as a
      diagnostic tool in countries with a high HIV prevalence. The low specificity of
      this scoring system leads to overdiagnosis of TB and unnecessary use of costly,
      antituberculous drugs. New tools for TB diagnosis in children in HIV-endemic
      areas are urgently needed.

PMID- 12000654
TI  - Measles in suburban Khartoum: an epidemiological and clinical study.
AB  - Clinical and epidemiological data were collected from 187 clinically diagnosed
      measles patients in Haj Yousif area, suburban Khartoum. Laboratory tests
      confirmed the diagnosis in 141 (75%) of the cases, but demonstrated that in 46
      (25%) patients the clinical symptoms were not caused by an acute measles virus
      (MV) infection. According to their vaccination card, 59% of the laboratory
      confirmed measles cases had been vaccinated for measles. Compared with non
      measles rash disease cases, confirmed measles cases more often had severe illness
      (P < 0.0001), were dehydrated (P=0.01) at presentation and less likely to recover
      without complications [OR 0.19 (95% CI 0.09, 0.39)]. There was no difference in
      death rate (P=0.20). Underweight [weight-for-age Z score (WAZ) <or= -2 SD] was an
      independent predictor of recovery with complications [OR 0.4 (95% CI 0.2, 0.99)].
      Severe measles cases (those who developed diarrhoea, pneumonia, otitis media,
      encephalitis or haemorrhagic rash) had similar vaccination rates and time
      intervals since vaccination as uncomplicated measles cases. Although severe
      measles had lower WAZ-scores (P=0.004), none of the nutritional parameters
      studied were predictive of outcome. Mortality was higher in the severe measles
      group [OR 8.8 (95% CI 1.7, 85.2)]. In 11 of 141 confirmed measles cases
      serological evidence of a recent infection with another virus was found, most
      commonly varicella zoster virus and dengue virus; spotted fever and rubella were
      among the most frequent diagnoses in 17 of 47 cases of the non-measles cases.

PMID- 12000655
TI  - Malaria control reinvented: health sector reform and strategy development in
      Colombia.
AB  - The consequences of health sector reforms on control of malaria were analysed
      using Colombia as an example. One of the most complex health sector reform
      programmes in Latin America took place in the 1990s; it included transferring the
      vertical vector-borne disease control (VBDC) programme into health systems at
      state and district levels. A series of studies was undertaken in 1998-2000 at the
      national level (Ministry of Health Study), at the state level (Departamento
      Study) and at the health district level (District Study) using formal and
      informal interviews among control staff and document analysis as data collection
      tools. A government-financed national training programme for VBDC staff - which
      included direct observation of control operations - was also used to analyse
      health workers' performance in the postreform period (longitudinal study). The
      results showed that some shortcomings of the old vertical system, such as the
      negative aspects of trade union activity, have not been overcome while some
      positive aspects of the old system, such as capacity building, operational
      planning and supervision have been lost. This has contributed to a decrease in
      control activity which, in turn, has been associated with more malaria cases.
      Malaria control had to be reinvented at a much larger scale than anticipated by
      the reformers caused by a whole series of problems: complex financing of public
      health interventions in the new system, massive staff reductions, the difficulty
      of gaining access to district and state budgets, redefining entire organizations
      and - in addition to the reforms - introducing alternative strategies based on
      insecticide-treated materials and the growth of areas of general insecurity in
      many parts of Colombia itself. However, positive signs in the transformed system
      include: the strengthening of central control staff (albeit insufficient in
      numbers) when transferred from the Ministry of Health to the National Institute
      of Health, the opportunities offered by the Basic Health Plan (PAB) for new
      planning initiatives and intersectoral co-operation and the integration of
      malaria diagnosis and treatment into the general health services (associated with
      a decrease of malaria mortality). The potentials of the new system have not yet
      been fully exploited: capacity building, communication and management skills need
      to be improved and it require guidance from the national level.

PMID- 12000656
TI  - Rabies post-exposure management in South Africa: a telephonic survey used as a
      rapid tool for operational research.
AB  - Rabies is an important disease in rural South Africa, and vaccine and
      immunoglobulin are provided, at the State's expense, to humans following
      suspected exposure to rabies virus by bite, scratch or mucosal splash. Health
      facilities where post-exposure treatment is available are listed, with contact
      telephone numbers, in national rabies guidelines. To verify the accuracy of this
      recently updated information, members of the national Rabies Advisory Group were
      tasked to complete a rapid survey. A simple standardized telephone interview
      technique was used. This revealed startling deficiencies in the availability of
      vaccine and immunoglobulin at the indicated sites and led to decisive corrective
      action. This 'quick and dirty' survey technique provided valuable information for
      improving an important public health programme, and should be considered when
      auditing other health programmes, particularly where a means for validating
      responses is readily available.

PMID- 12000657
TI  - People's perception of malaria in Mbarara, Uganda.
AB  - To understand people's perceptions of malaria and their implications for control
      programmes, we held focus group discussions (FGDs) and conducted semi-structured
      interviews (SSIs) with community members in Mbarara, Uganda. Mosquitoes were
      perceived as the cause or transmitters of malaria but the causation/transmission
      model of people differed from biomedical facts. Convulsions, a common
      complication of malaria, were perceived as a supernatural ailment, best treated
      by traditional medicine, as was splenomegaly. More than 70% of the patients with
      malaria had treatment from non-public health sources. This included self
      treatment (13%), use of traditional healers (12%) and use of private medical
      practitioners/pharmacists (69%). Although 26% (887/3309) used bednets to prevent
      malaria, only 7% of the nets were impregnated with insecticide. People who did
      not use bednets cited discomfort because of heat/humidity and their high cost as
      reasons. To improve malaria control in this area, people need to be educated on
      the connection between mosquitoes and malaria and on seeking biomedical treatment
      for convulsions. The malaria control programme could collaborate with traditional
      and private health care providers to increase promotion of insecticide
      impregnated mosquito nets.

PMID- 12000658
TI  - Humoral and cellular immune responses to glucose regulated protein 78 -- a novel
      Leishmania donovani antigen.
AB  - The recently cloned glucose regulated protein 78 (GRP78) of Leishmania donovani
      has been suggested as a new and promising Leishmania vaccine candidate. We
      assessed antibody and T-cell reactivity to GRP78 in an enzyme-linked
      immunosorbent assay (ELISA) and in lymphoproliferative assays. Serological
      evaluation of plasma samples obtained in Sudan revealed that 89% of patients with
      visceral leishmaniasis (VL), 78% with post kala-azar dermal leishmaniasis (PKDL),
      and 85% with cutaneous leishmaniasis (CL) had antibody reactivity to this
      Leishmania antigen. Plasma from healthy Sudanese individuals living in an area
      endemic for malaria but free of leishmaniasis and plasma from healthy Danes was
      negative in the assay. GRP78 antibody was detected in 10% and 5% of plasma
      samples from Sudanese and Ghanaian malaria patients, respectively, whereas 35% of
      plasma samples from otherwise healthy Sudanese individuals with a positive
      leishmanin skin test showed antibody reactivity to recombinant GRP78 (rGRP78). In
      lymphoproliferative assays, 9 of 13 isolates of peripheral blood mononuclear
      cells (PBMC) from individuals previously infected with L. donovani and one of
      three individuals previously infected with L. major showed a response to rGRP78,
      whereas PBMC isolates from Danish control individuals did not respond. These
      findings, in addition to our previous observations in experimental CL (Jensen et
      al. 2001), confirm GRP78 as a possible vaccine antigen.

PMID- 12000662
TI  - Dialogue with the author.

PMID- 12000663
TI  - The woven fabric - a metaphor of nursing care: the major subject in nursing
      education.
AB  - The woven fabric - a metaphor of nursing care: the major subject in nursing
      education Society's future needs regarding health care present challenges to
      traditional nursing education. Today, the ambition is to create a nursing role
      that is appropriate to people's health care needs rather than the needs of the
      health care system. In nursing education, the major subject - nursing care - is
      central. Accordingly, there is a need for a consistent and clear articulation of
      this subject as well as the nursing profession. The aim of the present study was
      to interpret and describe the major subject, its content and structure in the
      nursing programme at Malardalen University. With a hermeneutic approach an
      interpretation and application emerged as a metaphor of nursing care - the woven
      fabric. In this structure concepts function as bridges linking theory and
      practice, whereby it is possible to integrate different aspects of knowledge in
      order to think, feel and act nursing care.

PMID- 12000664
TI  - Normal oral, rectal, tympanic and axillary body temperature in adult men and
      women: a systematic literature review.
AB  - Normal oral, rectal, tympanic and axillary body temperature in adult men and
      women: a systematic literature review The purpose of this study was to
      investigate normal body temperature in adult men and women. A systematic review
      of data was performed. Searches were carried out in MEDLINE, CINAHL, and manually
      from identified articles reference lists. Studies from 1935 to 1999 were
      included. Articles were classified as (1) strong, (2) fairly strong and (3) weak
      evidence. When summarizing studies with strong or fairly strong evidence the
      range for oral temperature was 33.2-38.2 degrees C, rectal: 34.4-37.8 degrees C,
      tympanic: 35.4- 37.8 degrees C and axillary: 35.5-37.0 degrees C. The range in
      oral temperature for men and women, respectively, was 35.7-37.7 and 33.2-38.1
      degrees C, in rectal 36.7-37.5 and 36.8-37.1 degrees C, and in tympanic 35.5-37.5
      and 35.7-37.5 degrees C. The ranges of normal body temperature need to be
      adjusted, especially for the lower values. When assessing body temperature it is
      important to take place of measurement and gender into consideration. Studies
      with random samples are needed to confirm the range of normal body temperature
      with respect to gender and age.

PMID- 12000665
TI  - Are nurses able to assess fatigue, exertion fatigue and types of fatigue in
      residential home patients?
AB  - Are nurses able to assess fatigue, exertion fatigue and types of fatigue in
      residential home patients? Although fatigue is recognized as a subjective,
      generalized, extensive and disabling health care problem with a relatively high
      prevalence among the chronically ill, there have been no studies to show whether
      nurses caring for fatigued subjects are able to accurately assess the level of
      fatigue that exists in these patients. The aim of the present study is to
      investigate this issue. The following research questions are formulated: (1) To
      what degree do the assessments of fatigue and exertion fatigue given by nurses
      and patients agree? and (2) To what degree do the assessments of types of fatigue
      given by nurses and patients agree? The method adopted employed a correlational
      design approach applied to residential home patients and nurses. Data were
      gathered by questionnaire. Data collected from 44 selected patients and two
      assessors (nurses) for each patient are used in the analyses. Measurement
      instruments used are the Dutch fatigue scale (DUFS), the Dutch exertion fatigue
      scale (DEFS), types of fatigue and sociodemographic variables. Measurement
      correlations between the patients and the nurses, both for the DUFS and DEFS,
      showed fair agreement (fatigue and exertion fatigue) and slight agreement (types
      of fatigue). The main conclusion of this study is that nurses working in
      residential home care are unable, in comparison with the patients themselves, to
      accurately assess patient's fatigue (fair agreement), exertion fatigue (fair
      agreement) and types of fatigue (slight agreement).

PMID- 12000666
TI  - Assessment of pain, depression, and anxiety by visual analogue scale in Japanese
      women with rheumatoid arthritis.
AB  - Assessment of pain, depression, and anxiety by visual analogue scale in Japanese
      women with rheumatoid arthritis Visual analogue scales (VAS) of depression and
      anxiety were compared with standard full-length measures of these variables and
      with VAS of pain (VAS Pain). This was a good way to develop a practical
      methodology for the routine assessment of pain and affect in rheumatoid arthritis
      (RA) patients. The reliability of VAS Pain was studied by test-retest. The
      validity of VAS Pain in our sample was proved by correlations with the results of
      other tests. We also investigated the relationship between VAS Pain and C
      reactive protein (CRP). In 145 female RA patients, VAS of depression and anxiety
      were significantly correlated with full-length measures of these variables, and
      accounted for the majority of the explained variance in VAS Pain, while the full
      length standard measures contributed little more. In conclusion, VAS measurements
      of pain and affect were comprehensible, easily filled-out, and reliable in a
      sample of Japanese women with RA, and could capture some aspect of affective
      distress unique to RA patients.

PMID- 12000667
TI  - 'Carer and gatekeeper' - conflicting demands in nurses' experiences of telephone
      advisory services.
AB  - 'Carer and gatekeeper' - conflicting demands in nurses' experiences of telephone
      advisory services Millions of calls are made to the telephone advisory services
      in primary health care in Sweden. The patients seem happy with the advice and
      counselling they receive, but little has been written about nurses' experiences
      of performing telephone advisory services. Yet, the nurses are expected to be
      patient, sensitive and have a broad knowledge of medicine, nursing and pedagogy.
      The aim of this study was to describe how nurses experience the patient encounter
      when performing telephone advisory services. A strategic sample of five nurses
      were interviewed and asked to describe how they experienced the central aspects
      of the patient encounter by telephone. The transcribed interviews were analysed
      by the Empirical Phenomenological Psychological method. The nurses' experience of
      the patient encounter when performing telephone advisory services can be
      characterized in terms of the conflicting demands of being both carer and
      gatekeeper. The constituents of these conflicting demands were: reading between
      the lines while pressed for time; educating patients for self-care while fearful
      of misinterpreting the situation; encountering patients' satisfaction and
      dissatisfaction. The conflicting demands of being both professional carer and
      gatekeeper caused stress among the nurses. The organization of the telephone
      advisory services seems to hinder high-quality care.

PMID- 12000668
TI  - Decision-making in the treatment of elderly people: a cross-cultural comparison
      between Swedish and German physicians and nurses.
AB  - Decision-making in the treatment of elderly people: a cross-cultural comparison
      between Swedish and German physicians and nurses The aim of the study was to
      evaluate the comparability of decisions in the treatment of severely ill
      incompetent elderly patients among physicians and nurses from a cross-cultural
      perspective. Convenience samples of 192 doctors and 182 nurses from Germany and
      104 doctors and 122 nurses from Sweden have been investigated by a questionnaire
      in a cross-sectional study. Between 39 and 58% of the subjects in the various
      groups have chosen treatment options, which are not consistent with the patient's
      will. However, nurses showed a significantly higher compliance than doctors. The
      probability of choosing cardio-pulmonary resuscitation decreased with increasing
      information about the patient's wish. Ethical concerns and the patient's wishes
      appeared as the most important determinants of treatment decisions, whereas the
      hospital costs as well as the physicians' religion were of minor importance. The
      inconsistencies concerning decision- making within and between the groups reflect
      differences in underlying values and lack of societal consensus, which represent
      a prerequisite for the improvement of patient autonomy. To focus more frequently
      and to a larger extent onto the problems related to the treatment of severely ill
      elderly patients as well as onto the training of communication skills with an
      orientation towards informed consent in the medical training seems to be
      warranted.

PMID- 12000669
TI  - Dependency as disadvantage - patients' experiences.
AB  - Dependency as disadvantage - patients' experiences This is an empirical
      qualitative study of the dependent community patient. The investigation raises
      the question of what it is like to be a highly dependent patient and how they
      relate to the situation. A non-probability, volunteer sample was selected from
      home nursing patients in a large town in Norway. The data were collected through
      in-depth interviews with 15 patients in their home using a semistructured
      interview guide. A constant comparative approach was used for analysing data. The
      results show that dependency has disadvantages like constraints and burdens in
      daily life. The patient adjusts both in a reactive and proactive way. The
      constraints are apparent through reduced autonomy in daily life and limited
      possibilities for negotiation. The burden is demonstrated through uncertainty
      within the encounter situation, low esteem, and loss of privacy. Adjustment is
      made through planning, guidance of the carer, acceptance of the situation,
      positive self-image and by protection of family and carer, and placing blame on
      the bureaucracy. The patient reacts in a more passive, reactive way regarding
      circumstances connected to the health care system and in a more proactive way by
      trying to influence the situation in the interaction in the private sphere of the
      patient's home.

PMID- 12000670
TI  - Ethical issues in ethnographic nursing research with children and elderly people.
AB  - Ethical issues in ethnographic nursing research with children and elderly people
      The purpose of this article is to stimulate discussion on ethical issues in
      qualitative nursing research with children and elderly people. Both groups as
      informants of a qualitative study may need extra protection owing to their
      vulnerability. There are some references to these issues in articles dealing with
      nursing research ethics, but this subject is worthy of more debate. This article
      is based on the authors' experiences of working with informants in two
      ethnographic nursing studies. Especially difficult and important were those
      issues related to informed consent and the role of the researcher. The researcher
      has to respect the informants' humanity and ensure their autonomy, and be
      sensitive to their expressions and gestures in a reciprocal interaction
      throughout the research process.

PMID- 12000671
TI  - Psychiatric care and home care service - an exploration of the professional world
      encountered by persons with long-term mental illness.
AB  - Psychiatric care and home care service - an exploration of the professional world
      encountered by persons with long-term mental illness This study focuses on the
      views of professional health care providers within a geographical district in
      Sweden. A total of 52 interviews with persons representing different professional
      levels within psychiatry and the social services were conducted. The purpose was
      to compare their understanding of what their responsibility entailed as well as
      their perceptions of goals and required competence. A content analysis,
      supplemented with interpretations within a hermeneutic tradition, showed that
      there are both similarities and differences within and between the two
      organizations. A common finding is that professionals with the least education
      are to a great extent responsible for the practical care of persons with long
      term mental illness. The implication of this finding is that it is important to
      be aware of this division of responsibility when developing psychiatric nursing
      and the home care services according to the needs of long-term mentally ill
      patients.

PMID- 12000672
TI  - Self-reported sleep quality, strain and health in relation to perceived working
      conditions in females.
AB  - Self-reported sleep quality, strain and health in relation to perceived working
      conditions in females The aims of this study were to examine self-reported sleep
      quality, perceived strain and health in relation to working conditions; the
      prevalence and severity of sleep disturbances and daytime distress arising from
      poor sleep in women on different work shifts. Furthermore, to see whether females
      with gastrointestinal symptoms, joint-, back- or muscle-pain and who are
      dissatisfied with working hours differ with regard to the above aspects. Finally,
      degree of strain-related symptoms and sleep difficulties were tested as
      predictors of sleep quality and general health outcome. Important research
      questions are whether registered nurses and those on rotating work shifts have
      greater sleep problems than others. A total of 156 females, aged 20-59 years,
      working at three different casualty departments, answered structured
      questionnaires. The results showed a persistently high rate of psycho
      physiological long-term effects of stress related to working conditions. Thirty
      four per cent were dissatisfied with their working hours, and exhibited
      significantly more mental strain, fatigue/excessive tiredness and inability to
      relax after work because of involuntary thoughts, in relation to working
      conditions than others did. Sixty-two females (39.7%) complained of insufficient
      sleep. The sleep quality outcome was significantly predicted by difficulty
      falling asleep (odds ratio 8.4), difficulty in falling asleep after nocturnal
      awakening (odds ratio 3.4) and perceived exhaustion (odds ratio 2.6). Females
      suffering from gastrointestinal symptoms and joint-, back- and muscle symptoms
      for several days in a week or even everyday were especially sensitive to worse
      sleep quality. Independent of work shifts, registered nurses exhibited a higher
      degree of mental strain and prolonged recovery in comparison with others. In
      conclusions, sleep initiation difficulties, troubled sleep and exhaustion
      significantly predicted reduced sleep quality outcome with decreased resilience
      to stress and vulnerability to psycho-physiological disorders in females working
      within the health care system.

PMID- 12000673
TI  - Dental phobic patients' view of dental anxiety and experiences in dental care: a
      qualitative study.
AB  - Dental phobic patients' view of dental anxiety and experiences in dental care: a
      qualitative study The aim of this study was to explore and describe dental phobic
      patients' perceptions of their dental fear and experiences in dental care. The
      study sample consisted of 18 participants (12 women), with a mean age of 39.4
      years, selected consecutively from patients applying for treatment at a
      specialized dental fear clinic in Goteborg, Sweden. Dental fear, assessed by the
      Dental Anxiety Scale, showed score levels well over established levels for severe
      dental fear. The method for sampling and analysis was inspired by the constant
      comparative method for Grounded Theory (GT). The thematized in-depth interviews
      took place outside the clinic and lasted for 1-1.5 h. All the interviews were
      conducted by the first author (KHA), audiotaped and transcribed verbatim. Three
      higher-order categories were developed and labelled existential threat,
      vulnerability and unsupportive dentist. Existential threat was identified as the
      core category, describing the central meaning of the subjects' experiences in
      dental care. The core category included two dimensions, labelled threat of
      violation and threat of loss of autonomy and independence. The core category and
      the descriptive categories are integrated in a model framing the process of
      dental fear, as described by the informants. In conclusion, the onset of dental
      fear was commonly related to individual vulnerability and to traumatic dental
      care experiences, where perceived negative dentist behaviour played a significant
      role. The patient was caught in a 'vicious circle' that was difficult to break,
      and where fear and anxiety were maintained by negative expectations about
      treatment and about patient's own ability to cope in dental care situations.

PMID- 12000674
TI  - A theoretical extension of the concept of energy through an empirical study.
AB  - A theoretical extension of the concept of energy through an empirical study This
      paper extends the concept of energy as a multifaceted concept of the experience
      of energy and proposes a theoretical model regarding the understanding of the
      experience of energy. The hybrid model of concept development (Schwartz-Barcott
      and Kim, 2000) was used in a qualitative empirical study with a sample of
      athletes and chronically ill individuals. The concept of energy presented is a
      global concept and can be placed within the much-discussed concept of fatigue.
      Focusing on energy implicates a resource approach to individuals experiencing
      fatigue. A theoretical model for the experience of energy emerging from this
      study includes the subconcepts of the feeling of energy, perceived energy
      capacity, energy management, and performance of activities. Two sets of
      strategies within the concept of energy management are identified as energy
      economizing and energy generating. This article explores the potential of the
      concept of energy in describing fatigue as a health problem. Implications for
      clinical practice and further theoretical development are suggested.

PMID- 12000675
TI  - Nitrate signalling on the nitrate reductase gene promoter depends directly on the
      activity of the nitrate transport systems in Chlamydomonas.
AB  - Nitrate signalling on the nitrate reductase (Nia1) gene promoter from
      Chlamydomonas reinhardtii has been studied by using a construct of the Nia1
      promoter transcriptionally fused to the Chlamydomonas arylsulphatase gene as a
      reporter in strains bearing different sets of nitrate/nitrite transport genes.
      The high-affinity nitrate transport (HANT) system I is required for efficient
      signalling by nitrate, even at submicromolar concentrations of the anion. In
      addition, the autogenous regulation of nitrate reductase has been found to depend
      on the presence of system I. The low-affinity nitrate transport system III
      promoted signalling optimally on the promoter at millimolar nitrate
      concentrations. The HANT system IV, which is insensitive to ammonium and active
      at low CO2, allowed nitrate signalling at micromolar concentrations even in the
      presence of ammonium, suggesting that the balance of these two effectors controls
      Nia1 transcription. Our data indicate that nitrate signalling on the Nia1 gene
      promoter occurs intracellularly and depends on the activity of nitrate
      transporters.

PMID- 12000676
TI  - hoc: An Arabidopsis mutant overproducing cytokinins and expressing high in vitro
      organogenic capacity.
AB  - A novel Arabidopsis thaliana mutant, named hoc, was found to have an high
      organogenic capacity for shoot regeneration. The HOC locus may be involved in
      cytokinin metabolism leading to cytokinin-overproduction. In vitro, hoc root
      explants develop many shoots in the absence of exogenous growth regulators. The
      mutant displays a bushy phenotype with supernumerary rosettes and with normal
      phyllotaxy, resulting from precocious axillary meristem development. Genetic and
      molecular analyses show that the high shoot regeneration and the bushy phenotype
      are controlled by a recessive single gene, located on chromosome I, next to the
      GAPB CAPS marker. The mapping data and allelism tests reveal that the hoc mutant
      is not allelic to other reported Arabidopsis growth-regulator mutants. In
      darkness the hoc mutant is de-etiolated, with a short hypocotyl, opened
      cotyledons and true leaves. Growth regulator assays reveal that the mutant
      accumulates cytokinins at about two- and sevenfold the cytokinin level of wild
      type plants in its aerial parts and roots, respectively. Consequently, the
      elevated amounts of endogenous cytokinins in hoc plants are associated with high
      organogenic capacity and hence bushy phenotype. Thus hoc is the first cytokinin
      overproducing Arabidopsis mutant capable of auto-regenerating shoots without
      exogenous growth regulators.

PMID- 12000677
TI  - The IRE gene encodes a protein kinase homologue and modulates root hair growth in
      Arabidopsis.
AB  - We identified an Arabidopsis mutant, incomplete root hair elongation (ire), whose
      root hairs are about 40% shorter than the wild type owing to the early cessation
      of their growth. In contrast, the hy5 mutant has root hairs about twice as long
      as the wild type, possibly because of delayed cessation of growth. Thus IRE and
      HY5 are likely to modify the duration of growth of root hairs. We cloned the IRE
      locus using the T-DNA tagged line. The IRE locus encodes a protein that includes
      a serine/threonine protein kinase domain. The primary structure of this kinase
      domain shows significant similarity to a group of protein kinases among various
      eukaryotes. In the Arabidopsis genome there are at least three genes that are
      closely related to IRE. The IRE transcript was detected in every organ examined.
      However, the IRE promoter-GUS fusion gene was strongly expressed in the
      elongating root hair cells, suggesting the cell-autonomous function of IRE in
      root hairs. GUS activity was also detected in pollen grains, which develop by tip
      growth, suggesting that IRE has a common role in the tip growth of plant cells.

PMID- 12000678
TI  - Identification and regulation of high light-induced genes in Chlamydomonas
      reinhardtii.
AB  - We have used restriction fragment differential display for isolating genes of the
      unicellular green alga Chlamydomonas reinhardtii that exhibit elevated expression
      on exposure of cells to high light. Some of the high light-activated genes were
      also controlled by CO2 concentration. Genes requiring both elevated light and low
      CO2 levels for activation encoded both novel polypeptides and those that function
      in concentrating inorganic carbon (extracellular carbonic anhydrase, low CO2
      induced protein, ABC transporter of the MRP subfamily). All the genes in this
      category were shown to be under the control of Cia5, a protein that regulates the
      responses of C. reinhardtii to low-CO2 conditions. Genes specifically activated
      by high light, even under high-CO2 conditions, encoded a 30 kDa chloroplast
      membrane protein, a serine hydroxymethyltransferase, a nuclease, and two proteins
      of unknown function. Experiments using DCMU, an inhibitor of photosynthetic
      electron transport, and mutants devoid of either photosystem I or photosystem II
      activity, showed aberrant expression of all the genes regulated by both CO2 and
      high light, suggesting that redox plays a role in controlling their expression.
      In contrast, there was little effect of DCMU or lesions that block photosynthetic
      electron transport on the activity of genes that were specifically controlled by
      high light.

PMID- 12000679
TI  - Barley stripe mosaic virus-induced gene silencing in a monocot plant.
AB  - RNA silencing of endogenous plant genes can be achieved by virus-mediated,
      transient expression of homologous gene fragments. This powerful, reverse genetic
      approach, known as virus-induced gene silencing (VIGS), has been demonstrated
      only in dicot plant species, where it has become an important tool for functional
      genomics. Barley stripe mosaic virus (BSMV) is a tripartite, positive-sense RNA
      virus that infects many agriculturally important monocot species including
      barley, oats, wheat and maize. To demonstrate VIGS in a monocot host, we modified
      BSMV to express untranslatable foreign inserts downstream of the gammab gene, in
      either sense or antisense orientations. Phytoene desaturase (PDS) is required for
      synthesizing carotenoids, compounds that protect chlorophyll from photo
      bleaching. A partial PDS cDNA amplified from barley was 90, 88 and 74% identical
      to PDS cDNAs from rice, maize and Nicotiana benthamiana, respectively. Barley
      infected with BSMV expressing barley, rice or maize PDS fragments became photo
      bleached and accumulated phytoene (the substrate for PDS) in a manner similar to
      plants treated with the chemical inhibitor of PDS, norflurazon. In contrast,
      barley infected with wild-type BSMV, or BSMV expressing either N. benthamiana PDS
      or antisense green fluorescent protein (GFP), did not photo-bleach or accumulate
      phytoene. Thus BSMV silencing of the endogenous PDS was homology-dependent.
      Deletion of the coat protein enhanced the ability of BSMV to silence PDS. This is
      the first demonstration of VIGS in a monocot, and suggests that BSMV can be used
      for functional genomics and studies of RNA-silencing mechanisms in monocot plant
      species.

PMID- 12000680
TI  - The ethanolic fermentation pathway supports respiration and lipid biosynthesis in
      tobacco pollen.
AB  - Rapid pollen tube growth requires a high rate of sugar metabolism to meet
      energetic and biosynthetic demands. Previous work on pollen sugar metabolism
      showed that tobacco pollen carry out efficient ethanolic fermentation
      concomitantly with a high rate of respiration (Bucher et al., 1995). Here we show
      that the products of fermentation, acetaldehyde and ethanol, are further
      metabolised in a pathway that bypasses mitochondrial PDH. The enzymes involved in
      this pathway are pyruvate decarboxylase, aldehyde dehydrogenase and acetyl-CoA
      synthetase. Radiolabelling experiments show that during tobacco pollen tube
      growth label of 14C-ethanol is incorporated into CO2 as well as into lipids and
      other higher molecular weight compounds. A role for the glyoxylate cycle appears
      unlikely since activity of malate synthase, a key enzyme of the glyoxylate cycle,
      could not be detected.

PMID- 12000681
TI  - DNA binding and dimerization specificity and potential targets for the TCP
      protein family.
AB  - The TCP domain is a plant-specific DNA binding domain found in proteins from a
      diverse array of species, including the cycloidea (cyc) and teosinte branched1
      (tb1) gene products and the PCF1 and PCF2 proteins. To understand the role in
      transcriptional regulation of proteins with this domain, we have analysed the DNA
      binding and dimerization specificity of the TCP protein family using rice PCF
      proteins, and further evaluated potential targets for the TCP protein. The seven
      PCF members including five newly isolated proteins, were able to be grouped into
      two classes, I and II, based on sequence similarity in the TCP domain. Random
      binding site selection experiments and electrophoretic mobility shift assays
      (EMSAs) revealed the consensus DNA binding sequences of these two classes to be
      distinct but overlapping; GGNCCCAC for class I and GTGGNCCC for class II. The TB1
      protein from maize, which belongs to class II, had the same specificity as the
      rice class II proteins, suggesting the conservation of binding specificity
      between TCP domains from different species. The yeast 2-hybrid assay and EMSA
      revealed that these proteins tend to form a homodimer or a heterodimer between
      members of the same class. We searched predicted 5' flanking sequences of
      Arabidopsis genes for the consensus binding sequences and found that the
      consensus sites are distributed in the genome at a considerably lower frequency.
      We further analysed eight promoters containing the class I consensus TCP sites.
      The transcriptional activities of six promoters were decreased by a mutation of
      the TCP binding site, which is consistent with the observation that the class I
      TCP site can confer transactivation function on a heterologous promoter. These
      results suggest that the two classes of TCP protein are distinct in DNA binding
      specificity and transcriptional regulation.

PMID- 12000682
TI  - The WUSCHEL gene promotes vegetative-to-embryonic transition in Arabidopsis.
AB  - Formation of somatic embryos in plants is known to require high concentrations of
      auxin or 2,4-dichlorophenoxyacetic acid (2,4-D), which presumably acts to trigger
      a signalling cascade. However, very little is known about the molecular mechanism
      that mediates the vegetative-to-embryogenic transition. We have employed a
      genetic approach to dissect the signal transduction pathway during somatic
      embryogenesis. In a functional screen using a chemical-inducible activation
      tagging system, we identified two alleles of Arabidopsis gene PGA6 whose induced
      overexpression caused high-frequency somatic embryo formation in all tissues and
      organs tested, without any external plant hormones. Upon inducer withdrawal, all
      these somatic embryos were able to germinate directly, without any further
      treatment, and to develop into fertile adult plants. PGA6 was found to be
      identical to WUSCHEL (WUS), a homeodomain protein previously shown to be involved
      in specifying stem cell fate in shoot and floral meristems. Transgenic plants
      carrying an estradiol-inducible XVE-WUS transgene can phenocopy pga6-1 and pga6
      2. Our results suggest that WUS/PGA6 also plays a key role during embryogenesis,
      presumably by promoting the vegetative-to-embryogenic transition and/or
      maintaining the identity of the embryonic stem cells.

PMID- 12000683
TI  - The R1 gene for potato resistance to late blight (Phytophthora infestans) belongs
      to the leucine zipper/NBS/LRR class of plant resistance genes.
AB  - Late blight caused by the oomycete Phytophthora infestans is the most destructive
      disease in potato cultivation worldwide. New, more virulent P. infestans strains
      have evolved which overcome the genetic resistance that has been introgressed by
      conventional breeding from wild potato species into commercial varieties. R genes
      (for single-gene resistance) and genes for quantitative resistance to late blight
      are present in the germplasm of wild and cultivated potato. The molecular basis
      of single-gene and quantitative resistance to late blight is unknown. We have
      cloned R1, the first gene for resistance to late blight, by combining positional
      cloning with a candidate gene approach. The R1 gene is member of a gene family.
      It encodes a protein of 1293 amino acids with a molecular mass of 149.4 kDa. The
      R1 gene belongs to the class of plant genes for pathogen resistance that have a
      leucine zipper motif, a putative nucleotide binding domain and a leucine-rich
      repeat domain. The most closely related plant resistance gene (36% identity) is
      the Prf gene for resistance to Pseudomonas syringae of tomato. R1 is located
      within a hot spot for pathogen resistance on potato chromosome V. In comparison
      to the susceptibility allele, the resistance allele at the R1 locus represents a
      large insertion of a functional R gene.

PMID- 12000684
TI  - Regulation of Arabidopsis thaliana Em genes: role of ABI5.
AB  - In order to identify new factors involved in Em (a class I Late Embryogenesis
      Abundant protein) gene expression, Arabidopsis mutants with an altered expression
      of an Em promoter GUS fusion construct and a modified accumulation of Em
      transcripts and proteins were isolated. Germination tests on ABA showed that the
      most affected mutant had a weak abi phenotype. Complementation tests further
      revealed this mutant to be a new abi5 allele, consequently named abi5-5. In
      addition to reducing the final level of Em transcripts in the dry seed, the abi5
      5 mutation causes a delay in the accumulation of AtEm1 during seed development.
      An additional characteristic of the abi5-5 mutant, is the ability of its seeds to
      germinate at high concentrations of salt and mannitol. The abi5-5 mutation was
      characterized at the molecular level and was shown to result from a two base pair
      deletion in the coding sequence of the ABI 5 gene. The wild type and mutant
      recombinant proteins were produced in E. coli and were assayed for DNA-binding
      activity on their target promoters by electrophoretic mobility shift assay
      (EMSA). The ABI5 recombinant protein binds the ABRE sequence in the AtEm6
      promoter as shown by Dnase footprinting. Among the ABRE-type sequences selected
      on both Em promoters, the G-box type AGACACGTGGCATGT element of the AtEm6
      promoter shows the strongest binding by EMSA quantification.

PMID- 12000685
TI  - Patterns in abundance and diversity of faecally dispersed parasites of tiger in
      Tadoba National Park, central India.
AB  - BACKGROUND: Importance of parasites in ecological and evolutionary interactions
      is being increasingly recognized. However, ecological data on parasites of
      important host species is still scanty. We analyze the patterns seen in the
      faecal parasites of tigers in the Tadoba National Park, India, and speculate on
      the factors and processes shaping the parasite community and the possible
      implications for tiger ecology. RESULTS: The prevalence and intensities were high
      and the parasite community was dominated by indirect life cycle parasites. Across
      all genera of parasites variance scaled with the square of the mean and there was
      a significant positive correlation between prevalence and abundance. There was no
      significant association between different types of parasites. CONCLUSIONS: The 70
      samples analyzed formed 14 distinct clusters. If we assume each of the clusters
      to represent individual tigers that were sampled repeatedly and that resident
      tigers are more likely to be sampled repeatedly, the presumed transient tigers
      had significantly greater parasite loads than the presumed resident ones.

PMID- 12000686
TI  - Beverage specific alcohol intake in a population-based study: evidence for a
      positive association between pulmonary function and wine intake.
AB  - BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause
      mortality. Previous studies suggest that alcohol exposure may be linked to
      impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may
      be an important source of oxidants; however, wine contains several antioxidants.
      In this study we analyzed the relation of beverage specific alcohol intake with
      forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in
      a random sample of 1555 residents of Western New York, USA. METHODS: We expressed
      pulmonary function as percent of predicted normal FEV1 (FEV1%) and FVC (FVC%)
      after adjustment for height, age, gender and race. To obtain information on
      alcohol intake we used a questionnaire that reliably queries total alcohol and
      beverage specific recent (past 30 days) and lifetime alcohol consumption.
      RESULTS: Using multiple linear regression analysis after adjustment for
      covariates (pack-years of smoking, weight, smoking status, education, nutritional
      factors and for FEV1%, in addition, eosinophil count), we observed no significant
      correlation between total alcohol intake and lung function. However, we found
      positive associations of recent and lifetime wine intake with FEV1% and FVC%.
      When we analyzed white and red wine intake separately, the association of lung
      function with red wine was weaker than for white wine. CONCLUSION: While total
      alcohol intake was not related to lung function, wine intake showed a positive
      association with lung function. Although we cannot exclude residual confounding
      by healthier lifestyle in wine drinkers, differential effects of alcoholic
      beverages on lung health may exist.

PMID- 12000687
TI  - Psychosocial primary care - what patients expect from their General Practitioners
      A cross-sectional trial.
AB  - BACKGROUND: Psychosocial Primary Care (PPC) is a model of service delivery for
      patients with mental disorders and psychosocial problems which was established in
      Germany in 1987. This study was performed as part of the evaluation of a PPC
      training program. We investigated patients' expectations of the psychosocial
      treatment offered by GPs trained in PPC. METHODS: Ten general practitioners
      trained in PPC were randomly selected. Two hundred and twenty patients were
      surveyed in the waiting room regarding their expectations concerning
      psychological treatment. RESULTS: Eighty-five per cent of patients could envisage
      making use of psychosocial treatments. Counselling by the GP was considered most
      important (65%). Fifty-four per cent of patients indicated that there was
      sufficient counselling, but further distinctions revealed dissatisfaction with
      both the extent and content of the counselling. Lack of time was the most
      frequent reason (53%) cited for insufficient counselling. A willingness to
      discuss the psychological aspects of illness was exhibited by between 55%
      (current illness) and 79% of patients. Two-thirds of patients believed that
      discussing psychological aspects and counselling by the doctor could exert a
      healing effect or contribute to symptomatic improvement in physical illnesses.
      Younger patients and patients with experience in psychotherapy expected referral
      to mental health services. CONCLUSIONS: Primary care patients desire and accept
      psychological treatment from their GP. Training in psychosocial competence in
      primary care should be offered more frequently.

PMID- 12000688
TI  - The clinical effectiveness and cost-effectiveness of sibutramine in the
      management of obesity: a technology assessment.

PMID- 12000689
TI  - Promoting physical activity in South Asian Muslim women through "exercise on
      prescription".

PMID- 12000690
TI  - United Kingdom Radiation Oncology 1 Conference (UKRO 1): accuracy and uncertainty
      in radiotherapy.

PMID- 12000691
TI  - Nasopharyngeal carcinoma: treatments and outcomes in the 20th century.
AB  - Nasopharyngeal carcinoma (NPC), although rare in Europe and North America, is not
      uncommon in parts of Asia such as southern China and Hong Kong. Consequently,
      very few oncologists in the Western world have extensive experience in treating
      this neoplasm. Treatment using external beam therapy and/or brachytherapy evolved
      greatly during the 20th century and is still evolving, particularly with the use
      of adjunctive chemotherapy regimes. Diagnosis of NPC has also improved with the
      availability of CT and MRI. This worldwide review is divided into historical,
      transitional and modern eras, with the latter concerning 1971-2000. Currently,
      the most controversial aspects of NPC are recommendations for treatment of
      recurrent disease and the role of chemotherapy in the overall framework of
      treatment. Comparison of results from different centres is not possible without
      an understanding of the various staging systems that are, and have been, used; a
      comparison is given in this review. In the future, early diagnosis, adequate
      radiation dose to the primary with boost to bulky disease, and regular follow-up
      with biopsy of any suspicious residual or recurrent disease, are likely to become
      key issues to improve outcome. Also, apart from direct/indirect
      nasopharyngoscopy, the role of follow-up CT needs to be studied for early
      detection of residual or recurrent disease. More clinical trials on chemo
      radiation are also required, in order to study optimum doses and agents.

PMID- 12000692
TI  - Mycobacterium avium complex lung disease in immunocompetent patients: radiography
      CT correlation.
AB  - This study aimed to describe and correlate the chest radiography and CT findings
      of Mycobacterium avium complex (MAC) lung disease in immunocompetent patients. 26
      patients fulfilled The American Thoracic Society criteria for MAC lung disease
      and underwent chest radiography and CT within 6 weeks of positive cultures. All
      abnormalities and predominant lobar involvement were recorded and abnormalities
      on chest radiography were correlated with those on CT. The images were evaluated
      by two chest radiologists and decisions were reached by consensus. 21 females and
      5 males, with an overall mean age of 69 years, were included in the study. All
      chest radiographs and CT scans were abnormal. On chest radiography, overinflation
      was demonstrated in 18 patients. CT scan abnormalities included atelectasis
      (n=17), bronchiectasis (n=24), cavities (n=13), consolidation (n=3), emphysema
      (n=11), ground-glass opacity (n=8), linear opacities (n=26), mediastinal
      lymphadenopathy (n=3), nodules (n=25) and pleural disease (n=15). CT findings
      were at variance with chest radiography findings in 15 lobes. A new feature from
      this study is that the majority of patients with MAC lung disease demonstrate
      overinflation on chest radiography. 19% of cases had predominant upper lobe
      disease, indistinguishable from post-primary Mycobacterium tuberculosis
      infection. 77% of cases demonstrated the major imaging criteria of MAC lung
      disease. These are ill defined nodules, bronchiectasis, predominant middle lobe
      and/or lingular abnormalities, with or without overinflation. We believe that
      these characteristic radiological signs will assist the physician in the
      diagnostic work-up of patients with MAC lung disease.

PMID- 12000693
TI  - The use of stereotactic navigation guidance in minimally invasive transnasal
      nasopharyngectomy: a comparison with the conventional open transfacial approach.
AB  - The purpose of this paper is to study the efficacy of applying stereotactic
      navigation guidance to nasopharyngectomy via a minimally invasive transnasal
      approach as compared with the conventional open transfacial approaches. The
      nasopharynx is the centre of the anterior skull base, which is remote from the
      surface of the facial skeleton. It is well known that there are several surgical
      approaches for access to resect tumours from the nasopharynx. However, the open
      techniques have been associated with much morbidity and only provide access to,
      and identification of, the ipsilateral internal carotid artery that forms the
      lateral boundary and resection limit of the nasopharynx. The coupling of
      stereotactic navigation guidance and a minimally invasive transnasal approach for
      nasopharyngectomy allows the surgeon to identify and protect the internal carotid
      artery bilaterally at the nasopharynx. This technique reduces operating time and
      morbidity to a minimum and yet is oncologically sound for resecting
      nasopharyngeal lesions. We compare 15 patients who underwent the stereotactic
      navigation guidance approach with 20 patients who received a conventional open
      transfacial approach.

PMID- 12000694
TI  - Colour Doppler evaluation of ureteral jets in normal second and third trimester
      pregnancy: effect of patient position.
AB  - The study was designed to investigate the effect of patient position on the
      detection of ureteral jets in normal pregnancy. The number of jets was recorded
      for 1 min using colour Doppler ultrasound in 26 healthy asymptomatic gravid women
      between 16 weeks and 34 weeks gestation. Each patient was examined in the supine
      position and in both the right and left lateral decubitus positions. Ureteral
      jets were present on at least one side in 24 patients in the supine position
      compared with 26 women in the lateral decubitus position. 13 (54%) of the 24
      patients in whom jets were seen in the supine position had jets on only one side.
      A mean of 1.80 jets x min(-1) was detected on the right side and 3.23 jets x min(
      1) on the left (p=0.046) in the supine position. In the contralateral decubitus
      position, jets were detected on the right side in 22 (85%) women and on the left
      in 25 (96%) women. A mean of 3.07 jets x min(-1) was detected on the right and
      4.15 jets x min(-1) on the left. The difference in the frequency of ureteral jets
      between the supine and lateral decubitus positions was significant (p=0.004 for
      the right; p=0.011 for the left). However, the difference in the detection rate
      was significant on only the right side (p=0.016 for the right; p=0.063 for the
      left). 10 (77%) of 13 patients in whom unilateral absence of ureteral jets was
      noted had detectable jets in the lateral decubitus position. Our findings
      demonstrated the utility of the lateral decubitus position in the evaluation of
      ureters suspicious for obstruction. However, caution is still recommended in
      diagnosing ureteral obstruction if jets are persistently absent after this
      manoeuvre.

PMID- 12000695
TI  - Comparison of forward planned conformal radiation therapy and inverse planned
      intensity modulated radiation therapy for esthesioneuroblastoma.
AB  - The purpose of this study was to compare dose distribution of inverse planned
      intensity modulated radiation therapy (IMRT) with that of conformal radiation
      therapy (SCRT) in the treatment of esthesioneuroblastoma, and to report initial
      clinical results. 13 patients with esthesioneuroblastoma were planned both with
      IMRT and SCRT using complete three-dimensional data sets. A target dose of 60 Gy
      was prescribed. We performed a detailed dose volume histogram analysis. Dose
      coverage was equal in both plans while dose distribution was more conformal to
      the target volume with IMRT. Mean and maximum dose of the brain stem, chiasm,
      optic nerves and orbits were lower using IMRT than SCRT. The reduction was
      significant regarding orbit and optic nerve (p<0.05). IMRT was superior in
      sparing of organs at risk compared with SCRT. The additional sparing by IMRT was
      positively correlated to the size of the target volume, which was evident with
      target volumes above 200 cm3. Treatment time was approximately 20 minutes per
      fraction using IMRT compared with 15 minutes per fraction using SCRT. We conclude
      that IMRT is both feasible and a valuable tool for more conformal dose
      distribution in the treatment of esthesioneuroblastoma and to spare organs at
      risk that are in critical relationship to the tumour. This advantage could be
      seen especially well in complex shaped target volumes above 200 cm3. Thus, using
      IMRT, risk of complications may be minimized and local tumour control may be
      increased.

PMID- 12000696
TI  - Radiation doses in the UK trial of breast screening in women aged 40-48 years.
AB  - Although data have been published on the radiation doses involved in screening
      women in the UK in the age range 50-64 years, data have not been published for
      the screening of younger women, when one might expect higher doses and a
      different risk benefit balance. Therefore, data on the radiation doses arising
      from screening younger women (age range 40-48 years) as part of the UK age trial
      have been collected and reviewed. Each of the screening centres participating in
      the trial was asked to submit measurements of doses for samples of approximately
      50 or 100 women. The doses for 2296 women were received. The dose estimates were
      corrected to take account of variations in composition with age and breast
      thickness and in the spectra used. The average received dose was 2.5 mGy per
      oblique film and 2.0 mGy per craniocaudal film. Although these doses are about 7%
      higher than those calculated for the screening of older women, this was owing to
      differences in equipment rather than age of the women. Age itself was not found
      to be a significant factor affecting the dose to screened women aged over or
      under 50 years. An identifiable sub-group of women with larger breasts who were
      screened using higher dose systems received doses that were about 4.2 times the
      average, and should be considered in any risk benefit analysis. Where modern
      mammography systems with automatic beam quality selection and alternative target
      and filter materials had been introduced, there was a 15% reduction in average
      received dose and up to a 50% reduction in received dose for large breasts.

PMID- 12000697
TI  - Establishing radiological percutaneous gastrostomy with balloon-retained tubes as
      an alternative to endoscopic and surgical gastrostomy in patients with tumours of
      the head and neck or oesophagus.
AB  - The purpose of this study was to report our experience introducing radiological
      percutaneous gastrostomy (RPG) catheters at a hospital where hitherto only
      endoscopic and surgical methods have been used. The feasibility, success, time
      requirements, and complications of RPG were prospectively evaluated during a 12
      month period. 26 consecutive patients (median age 63 years, range 41-91 years)
      underwent gastropexy with T-fasteners followed by insertion of a 12-18 F balloon
      tube through a peel-away introducer and were followed-up clinically and
      radiologically. Success and complications occurring within 30 days were assessed.
      RPG was technically successful in all cases. Median procedure time was 34 min
      (range 20-90 min), median fluoroscopy time 6.9 min (range 2.3-30 min). 13
      surgical gastrostomies were avoided. One minor complication (peristomal leakage)
      occurred in a patient with gastric reflux and atony. Another patient destroyed
      the balloon of his tube by injecting food into the balloon port, which led to
      tube dislocation and peritonitis. In conclusion, radiological gastrostomy can be
      quickly learned by radiologists and is readily accepted by clinicians. It is an
      alternative to surgical gastrostomy when percutaneous endoscopic gastrostomy is
      not feasible, but can also be used as the primary method instead of the
      endoscopic method.

PMID- 12000698
TI  - Mesenteric panniculitis associated with abdominal tuberculous lymphadenitis: a
      case report and review of the literature.
AB  - Mesenteric panniculitis is a rare disease characterized by chronic non-specific
      inflammation of the mesenteric adipose tissue. The specific aetiology of the
      disease is previously unknown. A case diagnosed as mesenteric panniculitis is
      presented. The cause was biopsy-proved abdominal tuberculous lymphadenitis. To
      our knowledge, mesenteric panniculitis associated with tuberculosis infection has
      not been reported previously in the literature. Thus, we would like to present
      the first case and describe CT features of the disease.

PMID- 12000699
TI  - Small bowel obstruction due to incarcerated sciatic hernia: ultrasound diagnosis.
AB  - A 71-year-old woman presented with vomiting, abdominal pain and vague right
      gluteal discomfort. Abdominal ultrasound showed ascites and dilated small bowel
      loops with peristaltic movement, while transgluteal ultrasound revealed entrapped
      ascites beneath gluteal muscles and an oedematous, immobile bowel loop trapped
      between the sacrum and iliac bone with barely visible colour Doppler flow
      suggestive of an incarcerated sciatic hernia. CT demonstrated similar findings
      and subsequent surgery confirmed the diagnosis. To our knowledge, this is the
      first report of a pre-operative diagnosis of incarcerated sciatic hernia on
      ultrasound.

PMID- 12000700
TI  - Spinal ultrasound in infants.
AB  - This paper discusses the indications for spinal ultrasound, including its
      advantages and disadvantages compared with spinal MRI. The features and
      ultrasound findings both in normal infants and in those with spinal dysraphism
      are reviewed.

PMID- 12000701
TI  - The one that got away.

PMID- 12000704
TI  - Sugar creates a sticky business: round up the usual suspects.

PMID- 12000705
TI  - Metalloproteases and adipogenesis: a weighty subject.

PMID- 12000706
TI  - Bcl-2 expression inhibits liver carcinogenesis and delays the development of
      proliferating foci.
AB  - Tumor development is thought to require both increased proliferation and
      inhibition of apoptosis. However, the relationship between cell replication and
      cell death in liver tumorigenesis is complex because both proliferation and
      apoptosis increase during hepatocarcinogenesis. To investigate the effect of the
      anti-apoptotic gene Bcl-2 in liver carcinogenesis, we established a line of
      double transgenic mice that express transforming growth factor-alpha (TGF-alpha),
      a liver mitogen, and Bcl-2. Double transgenic mice, TGF-alpha and Bcl-2 single
      transgenics, and wild type received an injection of diethylnitrosamine at 15 days
      of age. This alkylating agent induces liver carcinogenesis and its effect is
      greatly enhanced by TGF-alpha. We report that Bcl-2 expression inhibited
      diethylnitrosamine-induced liver carcinogenesis and counteracted the enhancing
      effect of TGF-alpha. Bcl-2 delayed the growth of proliferative foci at the early
      stages of carcinogenesis and inhibited cell proliferation in these foci. The
      effect of Bcl-2 on liver carcinogenesis is consistent with its reported ability
      to interfere with cell replication. The data demonstrate that the expression of
      an anti-apoptotic gene during liver carcinogenesis causes a delay rather than an
      increase in tumorigenesis.

PMID- 12000707
TI  - Expression of histidine decarboxylase and synthesis of histamine by human small
      cell lung carcinoma.
AB  - We recently found that human small cell lung carcinomas (SCLCs) express, in
      addition to other neuroendocrine markers, vesicular monoamine transporters. Our
      present results indicate that SCLCs are histaminergic. We detected the
      biosynthetic enzyme histidine decarboxylase by immunohistochemistry in paraffin
      sections of 12 biopsies of SCLC tumors. This finding was supported by
      immunoblotting and reverse transcription-polymerase chain reaction experiments
      using established SCLC cell lines, frozen and paraffin-embedded SCLC tumors.
      Moreover, we found histamine to be synthesized, stored, and released by cultured
      SCLC cells. Our novel observations may be useful for developing new diagnostic
      tools for this frequent and highly malignant tumor.

PMID- 12000708
TI  - KIT mutations are common in incidental gastrointestinal stromal tumors one
      centimeter or less in size.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gut wall
      that express the receptor tyrosine kinase KIT. Somatic mutations that result in
      constitutive activation of KIT kinase have been identified in a number of studies
      of GISTs, although the reported frequency of these mutations has varied over a
      wide range (20 to 92%). Several reports have suggested that KIT gene mutations
      are more common in malignant GISTs than in benign lesions, and it has been
      proposed that mutations in exon 11 of KIT are a negative prognostic factor. To
      maximize sensitivity for KIT mutations we have adapted denaturing high-pressure
      liquid chromatography as a method for screening polymerase chain reaction
      amplimers of exons 9, 11, 13, and 17 from GIST genomic DNA. This approach was
      used to assess the frequency of KIT mutations in 13 morphologically benign,
      incidentally discovered, GISTs identified at autopsy, endoscopy, or laparotomy
      for unrelated disease. Representing the smallest pathologically recognizable
      GISTs, these lesions ranged in size from 4 to 10 mm in diameter and were all
      immunohistochemically positive for KIT. Eleven of the 13 tumors had sequence
      confirmed mutations in KIT, including 10 mutations in exon 11 (77%) and one
      mutation in exon 9 (7.7%). The remaining two tumors were wild type for exons 9,
      11, and 17; one of these was also analyzed for exon 13 and was wild type in this
      exon as well. The mutations found in the incidental GISTs were identical to those
      that have been documented in larger GISTs. In addition, the overall frequency of
      mutations in the incidental tumors (85%) did not differ significantly from that
      we previously reported in a series of 72 advanced/metastatic GISTs (86%),
      strongly supporting the view that activating mutations in KIT are acquired very
      early in the development of most GISTs. The findings suggest that KIT mutations
      per se are of little prognostic importance in GISTs.

PMID- 12000709
TI  - Aberrant methylation of preproenkephalin and p16 genes in pancreatic
      intraepithelial neoplasia and pancreatic ductal adenocarcinoma.
AB  - Pancreatic intraductal neoplasia (PanIN) is thought to be the precursor to
      infiltrating pancreatic ductal adenocarcinoma. We have previously shown that the
      preproenkephalin (ppENK) and p16 genes are aberrantly methylated in pancreatic
      adenocarcinoma. In this study we define the methylation status of the ppENK and
      p16 genes in various grades of PanINs. One hundred seventy-four samples (28
      nonneoplastic pancreatic epithelia, 7 reactive epithelia, 29 PanIN-1A, 48 PanIN
      1B, 27 PanIN-2, 14 PanIN-3, 15 invasive ductal adenocarcinomas, and 6
      miscellaneous pancreatic neoplasms) were microdissected from 29 formalin-fixed
      paraffin-embedded surgically resected pancreata, and were analyzed by methylation
      specific polymerase chain reaction. Fourteen of 15 (93.3%) invasive pancreatic
      ductal adenocarcinomas showed methylation of the ppENK gene and 4 of 15 (26.7%)
      showed methylation of the p16 gene. Nonneoplastic pancreatic epithelia did not
      harbor methylation of either gene. The prevalence of methylation of the ppENK
      gene increased significantly with increasing PanIN grade. A similar
      nonsignificant trend was noted for p16 methylation. Aberrant methylation of the
      ppENK gene was found in 7.7% of PanIN-1A, 7.3% of PanIN-1B, 22.7% of PanIN-2, and
      46.2% of PanIN-3. Aberrant methylation of the p16 gene was found in 12% of PanIN
      1A, 2.6% of PanIN-1B, 4.5% of PanIN-2, and 21.4% of PanIN-3. All but one of the
      PanINs from the 14 pancreata without pancreatic carcinoma was unmethylated with
      respect to either the p16 or ppENK gene. Our results suggest that methylation
      related inactivation of the ppENK and p16 genes is an intermediate or late event
      during pancreatic carcinogenesis. Because aberrant methylation of ppENK or p16
      was more often detected in similar grade PanINs from patients with pancreatic
      carcinoma than in those with other pancreatic diseases, it may be a useful
      indicator of the potential malignancy of epithelial cells of the pancreas.

PMID- 12000710
TI  - Cerebrovascular transforming growth factor-beta contributes to inflammation in
      the Alzheimer's disease brain.
AB  - Inflammatory mechanisms are thought to contribute to lesion pathogenesis and
      neuronal cell death in Alzheimer's disease. Transforming growth factor-beta (TGF
      beta) plays a central role in the response of the brain to injury, and is
      increased in the brain in Alzheimer's disease. In this study we determine whether
      expression of TGF-beta is abnormal in the microvasculature in Alzheimer's disease
      and whether TGF-beta affects vascular production of pro-inflammatory cytokines,
      interleukin (IL)-1 beta, and tumor necrosis factor (TNF)-alpha. Microvessels
      isolated from the cortices of Alzheimer's disease patients and age-matched
      controls are analyzed for microvessel-associated and released TGF-beta. Results
      from Western blot analysis and enzyme-linked immunosorbent assay indicate a
      higher level of TGF-beta in Alzheimer's disease vessels compared to controls. To
      determine whether TGF-beta affects vascular release of inflammatory factors,
      cultured brain endothelial cells are treated with TGF-beta and levels of IL-1
      beta and TNF-alpha determined. Both enzyme-linked immunosorbent assay and Western
      blot analyses show that untreated endothelial cells express little IL-1 beta or
      TNF-alpha, but incubation with TGF-beta results in robust expression of these
      factors by brain endothelial cells. Our results suggest that vessel-derived TGF
      beta contributes to inflammatory processes in the Alzheimer brain.

PMID- 12000711
TI  - Gold-facilitated in situ hybridization: a bright-field autometallographic
      alternative to fluorescence in situ hybridization for detection of Her-2/neu gene
      amplification.
AB  - Fluorescence in situ hybridization (FISH) represents an excellent method for
      profiling gene amplification in situ, but correlation with tissue morphology is
      difficult because of dark-field visualization. Validation of a bright-field assay
      for assessment of HER-2/neu gene amplification was investigated. Streptavidin
      Nanogold was used to generate bright-field gene copy signals using GoldEnhance
      gold-based autometallography, catalyzed reported deposition, and a biotin-labeled
      probe. One hundred cases of invasive breast carcinoma were evaluated for which
      FISH gene copy results, and mRNA and oncoprotein gene expression, were known.
      Autometallographic signals were qualitatively evaluable without the use of oil
      immersion microscopy. Results correlated well with indirect and direct label
      FISH. Autometallographic gold-based in situ hybridization represents a promising
      bright-field assay for the assessment of HER-2/neu gene amplification.

PMID- 12000712
TI  - A human immunoglobulin G1 antibody originating from an in vitro-selected Fab
      phage antibody binds avidly to tumor-associated MUC1 and is efficiently
      internalized.
AB  - We describe the engineering and characterization of a whole human antibody
      directed toward the tumor-associated protein core of human MUC1. The antibody PH1
      originated from the in vitro selection on MUC1 of a nonimmune human Fab phage
      library. The PH1 variable genes were reformatted for expression as a fully human
      IgG1. The resulting PH1-IgG1 human antibody displays a 160-fold improved apparent
      kd (8.7 nmol/L) compared to the kd of the parental Fab (1.4 micromol/L). In cell
      binding studies with flow cytometry and immunohistochemistry, PH1-IgG1 exhibits
      staining patterns typical for antibodies recognizing the tumor-associated tandem
      repeat region on MUC1, eg, it binds the tumor-associated glycoforms of MUC1 in
      breast and ovarian cancer cell lines, but not the heavily glycosylated form of
      MUC1 on colon carcinoma cell lines. In many tumors PH1-IgG1 binds to membranous
      and cytoplasmic MUC1, with often intense staining of the whole-cell membrane (eg,
      in adenocarcinoma). In normal tissues staining is either absent or less intense,
      in which case it is found mostly at the apical side of the cells. Finally,
      fluorescein isothiocyanate-labeled PH1-IgG1 internalizes quickly after binding to
      human OVCAR-3 cells, and to a lesser extent to MUC1 gene-transfected 3T3 mouse
      fibroblasts. The tumor-associated binding characteristics of this antibody, its
      efficient internalization, and its human nature, make PH1-IgG1 a valuable
      candidate for further studies as a cancer-targeting immunotherapeutic.

PMID- 12000713
TI  - Ligand-dependent genetic recombination in fibroblasts : a potentially powerful
      technique for investigating gene function in fibrosis.
AB  - Strategies for conditional induction of transgene expression in mice are likely
      to be valuable for testing the role of candidate genes in disease pathogenesis.
      We have developed a system for lineage-specific, ligand-dependent, induction of
      sustained transgene expression in fibroblastic cells in mice using a chimeric
      gene encoding the Cre-ER(T) fusion protein, under the control of a fibroblast
      specific regulatory sequence from the pro alpha 2(I)collagen gene. Cre-ER(T)
      operates as a tamoxifen-dependent DNA recombinase to excise fragments flanked by
      specific LoxP consensus sequences. To test efficiency and ligand dependency of
      this strategy, Cre-ER(T)-expressing mice were backcrossed with heterozygous
      ROSA26-LacZ reporter mice, in which a floxed-STOP cassette has been introduced
      upstream of a bacterial beta-galactosidase (LacZ) reporter gene at a ubiquitously
      expressed locus. Constitutive or tamoxifen-induced LacZ expression was examined
      in embryonic, neonatal, and adult compound-transgenic mice. When pregnant ROSA26
      LacZ females received a single dose of tamoxifen, high-level expression of LacZ
      in the skin was demonstrable from 24 hours after injection in double-transgenic
      embryos harboring both the Cre-ER(T) transgene and the target ROSA26-LacZ allele.
      High-level expression of LacZ was also induced postnatally by tamoxifen
      specifically in dermal and visceral fibroblasts. By allowing efficient embryonic
      or postnatal modification of alleles that have been targeted to incorporate LoxP
      sites, or to switch on transgenes cloned downstream of the floxed-STOP cassette,
      this system will allow fibroblast-specific genetic perturbations to be induced at
      predetermined embryonic or postnatal time points. This should greatly assist in
      in vivo functional studies of candidate genes in fibrotic diseases such as
      systemic sclerosis.

PMID- 12000714
TI  - Interaction between the transforming growth factor-beta type II receptor/Smad
      pathway and beta-catenin during transforming growth factor-beta1-mediated
      adherens junction disassembly.
AB  - The aim of the current study was to examine the influence of transforming growth
      factor (TGF)-beta 1 on proximal tubular epithelial cell-cell interaction, with
      particular emphasis on the regulation of adherens junction complex formation.
      Stimulation of the proximal tubular cell line HK-2 cells by TGF-beta 1 led to
      loss of cell-cell contact and disassembly of both adherens and tight junctional
      complexes. Adherens junction disassembly was associated with reduction of both
      Triton-soluble and Triton-insoluble E-cadherin, and an increase in detergent
      soluble beta-catenin. Under these conditions, immunoprecipitation and Western
      analysis demonstrated decreased association of beta-catenin, both with E
      cadherin, alpha-catenin, and the cell cytoskeleton. Confocal microscopy after
      immunostaining, showed decreased intensity of peripheral E-cadherin staining, and
      redistribution of beta-catenin expression to a perinuclear location. Tight
      junction disassembly was manifest by a reduction in the expression of Triton
      soluble occludin and ZO-1 by Western analysis and their disassociation manifested
      by immunostaining and confocal microscopy. Loss of cell-cell contact and
      disassembly of adherens junctions were seen after addition of TGF-beta 1 to the
      basolateral aspect of the cells. Immunoprecipitation experiments demonstrated co
      localization of E-cadherin, beta-catenin, and TGF-beta 1 RII in unstimulated
      cells. After TGF-beta 1 stimulation, the TGF-beta 1 RII no longer associated with
      either E-cadherin or beta-catenin. Dissociation of the adherens junction protein
      from the TGF-beta 1 receptor was associated with increased beta-catenin tyrosine
      phosphorylation and decreased threonine phosphorylation. Furthermore after
      receptor ligand binding, beta-catenin became associated with the TGF-beta 1
      signaling molecules Smad3 and Smad4.

PMID- 12000715
TI  - Vascular morphogenesis and differentiation after adoptive transfer of human
      endothelial cells to immunodeficient mice.
AB  - To establish a model for adoptive transfer of endothelial cells, we transferred
      human umbilical vein endothelial cells (HUVECs) to immunodeficient mice (Rag 2(-/
      )). HUVECs were suspended as single cells in Matrigel and injected subcutaneously
      in the abdominal midline. Within 10 days after injection, HUVECs expressed
      pseudopod-like extensions and began to accumulate in arrays. By day 20, we
      observed human vessels that contained erythrocytes, and on day 30 we observed
      perivascular cells that expressed smooth muscle actin, thus resembling mature
      vessels. Throughout the experimental period, HUVECs bound Ulex europaeus lectin
      and expressed CD31, VE-cadherin, von Willebrand factor, as well as ICAM-2. A
      fraction of the cells also expressed the proliferation marker Ki67. Moreover, the
      sialomucin CD34, which is rapidly down-regulated in cultured HUVECs, was
      reinduced in vivo. However, we found no reinduction of CD34 in cells cultured
      inside or on top of Matrigel in vitro. We also injected cells suspended in
      Matrigel around the catheter tip of implanted osmotic pumps. Delivery of
      recombinant human interferon-gamma by this route led to strong induction of MHC
      class II and ICAM-1 on the human vessels. In conclusion, isolated human
      endothelial cells can integrate with the murine vascular system to form
      functional capillaries and regain in vivo properties.

PMID- 12000716
TI  - Increased angiogenesis in the bone marrow of patients with systemic mastocytosis.
AB  - Recent data suggest that angiogenesis in the bone marrow (BM) is augmented and
      associated with growth of neoplastic cells in various hematological malignancies.
      Systemic mastocytosis (SM) is a neoplasm affecting multilineage and mast cell
      (MC)-committed hemopoietic progenitors. In the present study, we have assessed
      the BM microvessel density (MVD) by CD34 immunohistochemistry in 21 patients with
      SM, 5 with cutaneous mastocytosis (no BM infiltrates), and 5 control cases
      (normal BM). The median BM MVD was significantly higher in SM compared to
      cutaneous mastocytosis or controls (P < 0.05). In addition, a significant
      correlation (r = 0.74) between the BM MVD and grade of MC infiltration (percent
      tryptase(+) BM infiltrates) was found in SM. Moreover, the MVD was higher in MC
      infiltrates compared to the nonaffected adjacent marrow (P < 0.05).
      Immunohistochemical staining revealed expression of vascular endothelial growth
      factor in MC infiltrates. The notion that SM is associated with increased BM
      angiogenesis and vascular endothelial growth factor expression may have
      implications for the biology of disease and development of new treatment
      strategies.

PMID- 12000717
TI  - Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg
      cells.
AB  - We previously reported that ligand-independent signaling by highly expressed CD30
      in Hodgkin-Reed-Sternberg (H-RS) cells is responsible for constitutive activation
      of NF-kappa B. In the present study, we characterize the intracellular
      localization of tumor necrosis factor (TNF) receptor associated factor (TRAF)
      proteins in H-RS cells. Confocal immunofluorescence microscopy of cell lines
      derived from H-RS cells and HEK293 transformants highly expressing CD30 revealed
      aggregation of TRAF2 and TRAF5 in the cytoplasm as well as clustering near the
      cell membrane. In contrast, TRAF proteins were diffusely distributed in the
      cytoplasm in cell lines unrelated to Hodgkin's disease (HD) and control HEK293
      cells. Furthermore, the same intracellular distribution of TRAF proteins was
      demonstrated in H-RS cells of lymph nodes of HD, but not in lymphoma cells in
      lymph nodes of non-Hodgkin's lymphoma. Dominant-negative TRAF2 and TRAF5
      suppressed cytoplasmic aggregation along with constitutive NF-kappa B activation
      in H-RS cell lines. Confocal immunofluorescence microscopy also revealed co
      localization of IKK alpha, NIK, and I kappa B alpha with aggregated TRAF proteins
      in H-RS cell lines. These results suggest involvement of TRAF protein aggregation
      in the signaling process of highly expressed CD30 and suggest they function as
      scaffolding proteins. Thus, cytoplasmic aggregation of TRAF proteins appears to
      reflect constitutive CD30 signaling which is characteristic of H-RS cells.

PMID- 12000718
TI  - Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy
      bodies.
AB  - Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of
      Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3
      ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological
      hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled
      classical LBs in substantia nigra sections from four related human disorders:
      sporadic PD, inherited alphaS-linked PD, dementia with LBs (DLB), and LB
      positive, parkin-linked PD. Anti-parkin antibodies also detected LBs in
      entorhinal and cingulate cortices from DLB brain and alphaS inclusions in
      sympathetic gangliocytes from sporadic PD. Double labeling with confocal
      microscopy of DLB midbrain sections revealed that approximately 90% of anti-alpha
      S-reactive LBs were also detected by a parkin antibody to amino acids 342 to 353.
      Accordingly, parkin proteins, including the 53-kd mature isoform, were present in
      affinity-isolated LBs from DLB cortex. Fluorescence resonance energy transfer and
      immunoelectron microscopy showed that alphaS and parkin co-localized within
      brainstem and cortical LBs. Biochemically, parkin appeared most enriched in
      cytosolic and postsynaptic fractions of adult rat brain, but also in purified,
      alpha S-rich presynaptic elements that additionally contained parkin's E2-binding
      partner, UbcH7. We conclude that parkin and UbcH7 are present with alphaS in
      subcellular compartments of normal brain and that parkin frequently co-localizes
      with alpha S aggregates in the characteristic LB inclusions of PD and DLB. These
      results suggest that functional parkin proteins may be required during LB
      formation.

PMID- 12000719
TI  - Human endomucin: distribution pattern, expression on high endothelial venules,
      and decoration with the MECA-79 epitope.
AB  - Endomucin is a typical sialomucin that we recently identified on the surface of
      mouse endothelial cells and on putative hematopoetic clusters of the dorsal aorta
      in the embryo. We have generated a panel of monoclonal antibodies (mAbs) against
      the extracellular part of human endomucin and polyclonal antibodies against the
      cytoplasmic part. Using immunohistochemistry endomucin was specifically detected
      on endothelial cells of blood and lymphatic vessels of all analyzed human
      tissues. In addition, the polyclonal antibodies stained the epithelium of the
      epidermis as well as epithelial and myoepithelial cells of the eccrine and
      apocrine glands in the skin. This nonendothelial staining could only be seen with
      a subset of mAbs if the staining procedure was amplified. Although high
      endothelial venules (HEVs) were not significantly stained with mAbs against
      endomucin, the polyclonal antibodies clearly detected endomucin on HEVs in
      lymphatic organs of the mouse and human, suggesting HEV-specific glycosylation
      affecting recognition by the mAbs. Indeed, endomucin isolated from human and
      mouse lymphoid organs carried the MECA-79 epitope that defines a set of L
      selectin ligands on HEVs called peripheral node addressins. We conclude that
      human and mouse endomucin are endothelial sialomucins with the potential to
      function as L-selectin ligands.

PMID- 12000720
TI  - Suppression of diabetic retinopathy with angiopoietin-1.
AB  - Diabetic retinopathy remains a leading cause of irreversible blindness. A
      critical early pathology in the disease is the adhesion of leukocytes to the
      retinal vasculature, a process that occurs, in part, via intercellular adhesion
      molecule-1. Once leukocyte adhesion occurs, endothelial cell injury ensues, as
      does blood-retinal barrier breakdown. Here we show that angiopoietin-1 can
      prevent and reverse these diabetic retinal vascular changes in both new and
      established diabetes. Angiopoietin-1, when given intravitreally to newly diabetic
      rats, normalized retinal vascular endothelial growth factor (VEGF) and
      intercellular adhesion molecule-1 mRNA and protein levels, leading to reductions
      in leukocyte adhesion, endothelial cell injury, and blood-retinal barrier
      breakdown. When an adenovirus coding for angiopoietin-1 was given systemically to
      mice with established diabetes, it similarly inhibited leukocyte adhesion and
      endothelial cell injury and blood-retinal barrier breakdown. These changes
      coincided with reductions in retinal eNOS, nitric oxide, Akt (protein kinase B),
      and MAP kinase activity, known mediators of VEGF bioactivity and leukocyte
      adhesion. When endogenous VEGF bioactivity was inhibited with a soluble Flt-1/Fc
      chimera, retinal Akt kinase activity was significantly reduced in vivo. Taken
      together, these data document new vascular and anti-inflammatory bioactivities
      for angiopoietin-1 and identify it as the first naturally occurring protein that
      directly protects the retinal vasculature in diabetes.

PMID- 12000721
TI  - Altered Notch ligand expression in human liver disease: further evidence for a
      role of the Notch signaling pathway in hepatic neovascularization and biliary
      ductular defects.
AB  - The Jagged and Delta family of transmembrane proteins are ligands for Notch
      receptors, which control the proliferation and/or differentiation of many cell
      lineages. Expression and localization of these ligands in the adult human liver
      has not been fully elucidated, nor whether dysregulation of these proteins
      contributes to liver disease processes. We have examined expression of the five
      known Notch ligands in human liver. Expression of Jagged-1 and Delta-4 mRNA was
      seen in normal and diseased liver tissue, whereas Jagged-2, Delta-1, and Delta-3
      mRNA was undetectable. In primary liver cell isolates, Jagged-1 expression was
      found in all cell types, whereas Delta-4 was present in biliary epithelial and
      liver endothelial cells, but absent in hepatocytes. Interestingly, Jagged-1 mRNA
      expression was significantly up-regulated in diseased liver tissue. By
      immunohistochemistry, Jagged-1 expression was present on most structures in
      normal tissue. However in disease, strikingly strong Jagged-1 immunoreactivity
      was observed on many small neovessels and bile ductules. The expression of
      downstream modulators and effectors of Notch signaling was also detectable in
      purified cell isolates. This, together with aberrant Jagged-1 expression suggests
      that the Notch signaling pathway may play a role in the neovascularization and
      biliary defects observed in the liver during the development of cirrhosis.

PMID- 12000722
TI  - The role of hepatic stellate cells and transforming growth factor-beta(1) in
      cystic fibrosis liver disease.
AB  - Liver disease causes significant morbidity and mortality from multilobular
      cirrhosis in patients with cystic fibrosis. Abnormal bile transport and biliary
      fibrosis implicate abnormal biliary physiology in the pathogenesis of cystic
      fibrosis-associated liver disease (CFLD), yet the mediators linking biliary
      events to fibrosis remain unknown. Activated hepatic stellate cells (HSCs) are
      the pre-eminent mediators of fibrosis in a range of hepatic disorders. The
      dominant stimulus for matrix production by HSCs is the cytokine transforming
      growth factor (TGF)-beta(1). In CFLD, the role of HSCs and the source of TGF
      beta(1) have not been evaluated. Liver biopsy tissue obtained from 38 children
      with CFLD was analyzed. Activated HSCs, identified by co-localization of
      procollagen alpha(1)(I) mRNA and alpha-smooth muscle actin, were demonstrated as
      the cellular source of excess collagen production in the fibrosis surrounding the
      bile ducts and the advancing edge of scar tissue. TGF-beta protein and TGF
      beta(1) mRNA expression were shown to be predominantly expressed by bile duct
      epithelial cells. TGF-beta(1) expression was significantly correlated with both
      hepatic fibrosis and the percentage of portal tracts showing histological
      abnormalities associated with CFLD. This study demonstrates a definitive role for
      HSCs in fibrogenesis associated with CFLD and establishes a potential mechanism
      for the induction of HSC collagen gene expression through the production of TGF
      beta(1) by bile duct epithelial cells.

PMID- 12000723
TI  - Peripheral blood and granuloma CD4(+)CD28(-) T cells are a major source of
      interferon-gamma and tumor necrosis factor-alpha in Wegener's granulomatosis.
AB  - To elucidate whether the fraction of CD28(-) T cells within the CD4(+) T-cell
      population is a major source of Th1-like and proinflammatory cytokine production
      driving Wegener's granulomatosis (WG) granuloma formation, we analyzed the
      phenotype and functional characteristics of peripheral blood CD4(+)CD28(-) T
      cells and of T cells in granulomatous lesions of 12 patients with active WG.
      Surface markers and intracytoplasmic cytokine and perforin expression were
      assessed by flow cytometry. Cytokine secretion was measured by enzyme-linked
      immunosorbent assay. Immunohistological studies demonstrated interferon-gamma and
      tumor necrosis factor-alpha cytokine positivity attributable to CD4(+)CD28(-) T
      cells in granulomatous lesions. Peripheral blood CD4(+)CD28(-) T cells expressed
      CD57, also found on natural killer cells, and intracytoplasmic perforin. They
      were generally CD25 (interleukin-2 receptor)-negative. CD18 (adhesion molecule
      beta(2)-integrin) was strongly up-regulated on CD4(+)CD28(-) T cells, whereas
      only a minority of CD4(+)CD28(+) T cells expressed CD18. CD4(+)CD28(-) T cells
      appeared as a major source of interferon-gamma and tumor necrosis factor-alpha.
      In contrast, CD4(+)CD28(+) T cells were able to produce and secrete a wider
      variety of cytokines including interleukin-2. One-quarter of CD4(+)CD28(+) T
      cells expressed the activation marker CD25, but they lacked perforin. Thus,
      CD4(+)CD28(-) T cells appeared more differentiated than CD4(+)CD28(+) T cells.
      They displayed Th1-like cytokine production and features suggestive of the
      capability of CD4(+) T-cell-mediated cytotoxicity. CD4(+)CD28(-) T cells may be
      recruited into granulomatous lesions from the blood via CD18 interaction, and may
      subsequently promote monocyte accumulation and granuloma formation through their
      cytokine secretion in WG.

PMID- 12000724
TI  - Tau and alpha-synuclein pathology in amygdala of Parkinsonism-dementia complex
      patients of Guam.
AB  - Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a
      progressive neurodegenerative disorder of Chamorro residents of Guam and the
      Mariana Islands, characterized by abundant neuron loss and tau neurofibrillary
      pathology similar to that observed in Alzheimer's disease (AD). A variety of
      neurodegenerative diseases with tau pathology including ALS/PDC also have alpha
      synuclein positive pathology, primarily in the amygdala. We further characterized
      the tau and alpha-synuclein pathology in the amygdala of a large series of 30
      Chamorros using immunohistochemical and biochemical techniques. Tau pathology was
      readily detected in both affected and unaffected Chamorros. In contrast, alpha
      synuclein pathology was detected in 37% of patients with PDC but not detected in
      Chamorros without PDC or AD. The alpha-synuclein aggregates often co-localized
      within neurons harboring neurofibrillary tangles suggesting a possible
      interaction between the two proteins. Tau and alpha-synuclein pathology within
      the amygdala is biochemically similar to that observed in AD and
      synucleinopathies, respectively. Thus, the amygdala may be selectively vulnerable
      to developing both tau and alpha-synuclein pathology or tau pathology may
      predispose it to synuclein aggregation. Furthermore, in PDC, tau and alpha
      synuclein pathology occurs independent of beta-amyloid deposition in amygdala
      thereby implicating the aggregation of these molecules in the severe
      neurodegeneration frequently observed in this location.

PMID- 12000725
TI  - Adenoviral transfer of murine oncostatin M elicits periosteal bone apposition in
      knee joints of mice, despite synovial inflammation and up-regulated expression of
      interleukin-6 and receptor activator of nuclear factor-kappa B ligand.
AB  - Oncostatin M (OSM) has been described as a bone-remodeling factor either
      stimulating osteoblast activity or osteoclast formation in vitro. To elucidate
      the in vivo effect of OSM on bone remodeling, we injected an adenoviral vector
      encoding murine OSM in knee joints of mice. OSM strongly induced interleukin (IL)
      6 gene expression, a known mediator of osteoclast development. We investigated
      the OSM effect in wild-type and IL-6-deficient mice and found a similar degree of
      OSM-induced joint inflammation. Within the first week of inflammation, the
      periosteum along the femur and tibia increased in cell number and stained
      positive for the osteoblast marker alkaline phosphatase. At these sites bone
      apposition occurred in both strains as demonstrated by Goldner and Von Kossa
      staining. In vitro OSM enhanced the effect of bone morphogenetic protein-2 on
      osteoblast differentiation. Immunohistochemistry demonstrated expression of
      receptor activator of nuclear factor-kappa B ligand (RANKL) and its receptor,
      receptor activator of nuclear factor-kappa B (RANK), in the periosteum but
      osteoclasts were not detected at sites of bone apposition. Induced mRNA
      expression for the receptor activator of nuclear factor-kappa B ligand inhibitor
      osteoprotegerin probably controlled osteoclast development during OSM
      overexpression. Our results show that OSM favors bone apposition at periosteal
      sites instead of resorption in vivo. This effect was not dependent on or
      inhibited by IL-6.

PMID- 12000726
TI  - Characterization of gene expression profiles in intraductal papillary-mucinous
      tumors of the pancreas.
AB  - The molecular pathology of precursor lesions leading to invasive pancreatic
      ductal adenocarcinomas remains relatively unknown. We have applied cDNA
      microarray analysis to characterize gene expression profiles in a series of
      intraductal papillary-mucinous tumors (IPMTs) of the pancreas, which represents
      one of the alternative routes of intraepithelial progression to full malignancy
      in the pancreatic duct system. Using a cDNA microarray containing 4992 human
      genes, we screened a total of 13 IPMTs including nine noninvasive and four
      invasive cases. Expression change in more than half of the tumors was observed
      for 120 genes, ie, 62 up-regulated and 58 down-regulated genes. Some of the up
      regulated genes in this study have been previously described in classical
      pancreatic carcinomas such as lipocalin 2, galectin 3, claudin 4, and cathepsin
      E. The most highly up-regulated genes in IPMTs corresponded to three members of
      the trefoil factor family (TFF1, TFF2, and TFF3). Immunohistochemistry performed
      on five genes found to be differentially expressed at the RNA level (TFF1, TFF2,
      TFF3, lipocalin 2, and galectin 3) showed a good concordance between transcript
      level and protein abundance, except for TFF2. Hierarchical clustering organized
      the cases according to the dysplastic and invasive phenotype of theIPMTs. This
      analysis has permitted us to implicate several genes (caveolin 1, glypican 1,
      growth arrest-specific 6 protein, cysteine-rich angiogenic inducer 61) in tumor
      progression. The observation that several genes are differentially expressed both
      in IPMTs and pancreatic carcinomas suggests that they may be involved at an early
      stage of pancreatic carcinogenesis.

PMID- 12000727
TI  - Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14
      transgenic mice after ischemia and reperfusion injury.
AB  - TSG-14/PTX3 is a gene inducible by tumor necrosis factor (TNF)-alpha, interleukin
      1 beta, and lipopolysaccharide in fibroblasts, macrophages, and endothelial
      cells. It encodes a 42-kd secreted glycoprotein that belongs to the pentraxin
      family of acute-phase proteins. Recently, we demonstrated that TSG-14 transgenic
      mice (TSG-14tg) overexpressing the murine TSG-14 gene under control of its own
      promoter are more resistant to lipopolysaccharide-induced shock and to
      polymicrobial sepsis caused by cecal ligation and puncture. Here we show that
      after ischemia and reperfusion (I/R) injury, TSG-14tg mice have an impaired
      survival rate, which appeared secondary to a markedly increased inflammatory
      response, as assessed by the local (duodenum and ileum) and remote (lung)
      enhancement in vascular permeability, hemorrhage, and neutrophil accumulation.
      Moreover, tissue concentrations of TNF-alpha, interleukin-1 beta, KC, and MCP-1
      were higher in TSG-14tg as compared to wild-type mice after I/R injury. Of note,
      elevated TNF-alpha concentrations in serum were only observed in TSG-14tg mice
      and blockage of TNF-alpha action prevented lethality of TSG-14tg mice. These
      results demonstrate that transgenic expression of TSG-14 induces an enhanced
      local and systemic injury and TNF-alpha-dependent lethality after I/R. Taken
      together, our data point to a critical role of TSG-14 in controlling acute
      inflammatory response in part via the modulation of TNF-alpha expression.

PMID- 12000728
TI  - Carp, a cardiac ankyrin-repeated protein, and its new homologue, Arpp, are
      differentially expressed in heart, skeletal muscle, and rhabdomyosarcomas.
AB  - Arpp, a protein containing an ankyrin repeat domain, PEST sequence, and proline
      rich region, is a novel ankyrin-repeated protein highly homologous to Carp, which
      is proposed to be the putative genetic marker for cardiac hypertrophy. In this
      study, we comparatively analyzed expression of Arpp and Carp protein in skeletal
      and cardiac muscles and rhabdomyosarcomas (RMSs). In adult skeletal muscle, Arpp
      was preferentially expressed in the nucleus and cytoplasm of type I fibers,
      whereas Carp was barely detectable in skeletal muscle. On the other hand, in
      adult cardiac muscle, interestingly, Arpp was expressed in ventricles mostly,
      whereas Carp was expressed throughout the atrium and ventricle. Furthermore,
      although Carp was identified in fetal heart at 11 developmental weeks, Arpp was
      very low or undetectable in these fetal hearts. These results suggest that Arpp
      and Carp are differentially expressed and function in both skeletal and cardiac
      muscle of fetus and adult. We found that Arpp expression was induced during the
      differentiation of C2C12 cells in vitro, suggesting that Arpp-expression may be
      associated with the differentiation stage during myogenesis. Both Arpp and Carp
      were found to be expressed in all of the RMS cases studied. Because the
      expression patterns of Arpp in RMS were different from those of muscle actin or
      desmin, Arpp may be detectable in RMS cases that do not express other existing
      RMS markers.

PMID- 12000729
TI  - Diminished callus size and cartilage synthesis in alpha 1 beta 1 integrin
      deficient mice during bone fracture healing.
AB  - Integrins mediate cell adhesion to extracellular matrix components. Integrin
      alpha 1 beta 1 is a collagen receptor expressed on many mesenchymal cells, but
      mice deficient in alpha 1 integrin (alpha1-KO) have no gross structural defects.
      Here, the regeneration of a fractured long bone was studied in alpha1-KO mice.
      These mice developed significantly less callus tissue than the wild-type (WT)
      mice, and safranin staining revealed a defect in cartilage formation. The mRNA
      levels of nine extracellular matrix genes in calluses were evaluated by Northern
      blotting. During the first 9 days the mRNA levels of cartilage-related genes,
      including type II collagen, type IX collagen, and type X collagen, were lower in
      alpha1-KO mice than in WT mice, consistent with the reduced synthesis of
      cartilaginous matrix appreciated in tissue sections. Histological observations
      also suggested a diminished number of chondrocytes in the alpha 1-KO callus.
      Proliferating cell nuclear antigen staining revealed a reduction of mesenchymal
      progenitors at the callus site. Although, the number of mesenchymal stem cells
      (MSCs) obtained from WT and alpha 1-KO whole marrow was equal, in cell culture
      the proliferation rate of the MSCs of alpha 1-KO mice was slower, recapitulating
      the in vivo observation of reduced callus cell proliferation. The results
      demonstrate the importance of proper collagen-integrin interaction in fracture
      healing and suggest that alpha1 integrin plays an essential role in the
      regulation of MSC proliferation and cartilage production.

PMID- 12000730
TI  - Expression of transforming growth factor-beta 1 by pancreatic stellate cells and
      its implications for matrix secretion and turnover in chronic pancreatitis.
AB  - Pancreatic stellate cells mediate fibrosis in chronic pancreatitis. Matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)-1
      and -2 are crucial modulators of fibrosis. Transforming growth factor-beta (TGF
      beta) is a key regulator of extracellular matrix production and myofibroblast
      proliferation. We have examined MMP and TIMP synthesis by transformed cultured
      pancreatic stellate cells and their regulation by TGF-beta 1. By Northern
      analysis they expressed mRNAs for procollagen 1, TIMP-1, TIMP-2, and MMP-2.
      Expression of membrane type-1 MMP was confirmed by Western blotting. By
      immunohistochemistry these enzymes localized to fibrotic areas in human chronic
      pancreatitis. Active TGF-beta 1 constitutes 2 to 5% of total TGF-beta 1 secreted
      by pancreatic stellate cells; they express TGF-beta receptors I and II. Exogenous
      TGF-beta 1 (10 ng/ml) significantly increased procollagen-1 mRNA by 69% and
      collagen protein synthesis by 34%. Similarly TGF-beta 1 at 0.1, 1, and 10 ng/ml
      significantly reduced cellular proliferation rate by 37%, 44%, and 44%,
      respectively, whereas pan-TGF-beta-neutralizing antibody increased proliferation
      by 40%. TGF-beta1 (10 ng/ml) down-regulated MMP-9 by 54% and MMP-3 by 34% whereas
      TGF-beta 1-neutralizing antibody increased MMP-9 expression by 39%. Pancreatic
      stellate cells express both mediators of matrix remodeling and the regulatory
      cytokine TGF-beta 1 that, by autocrine inhibition of MMP-3 and MMP-9, may enhance
      fibrogenesis by reducing collagen degradation.

PMID- 12000731
TI  - Mapping and gene expression profile of the minimally overrepresented 8q24 region
      in prostate cancer.
AB  - We have recently reported that overrepresentation of 8q24 (c-myc) is associated
      with clinical progression in prostate cancer. In this study, we map the
      boundaries of the overrepresented region within 8q23-q24 using interphase
      fluorescent in situ hybridization analysis of paraffin-embedded prostate cancer
      specimens. One hundred primary prostate cancers and three prostate cancer cell
      lines were evaluated, and the minimally overrepresented region could be narrowed
      to the approximately 8.2-Mb region between D8S514 and H47317. This region
      includes c-myc and is wholly within 8q24. Eukaryotic translation initiation
      factor 3 subunit 3 does not seem to be overrepresented independent of c-myc in
      prostate cancer. The cell lines PC3 and DU145 have and do not have 8q24
      overrepresentation, respectively. We then selected 39 expressed sequence tags
      (ESTs) within and surrounding the minimally overrepresented region and performed
      expression analysis using Northern blot hybridization. Five ESTs/genes including
      c-myc were overexpressed in both the PC3 cell line and DU145, but the PC3 to
      DU145 expression ratios were <2. Seven ESTs were overexpressed twofold or more in
      PC3 compared to DU145. This group included hyaluronan synthase 2, nephroblastoma
      overexpressed gene, eukaryotic translation initiation factor 3 subunit 3, and an
      EST (R69368) encoding a hypothetical protein (BM009). These seven genes as well
      as c-myc are candidate target genes within the overrepresented 8q24 region and
      their overexpression may be associated with prostate cancer progression.

PMID- 12000732
TI  - The lysosomal protease cathepsin L is an important regulator of keratinocyte and
      melanocyte differentiation during hair follicle morphogenesis and cycling.
AB  - We have previously shown that the ubiquitously expressed lysosomal cysteine
      protease, cathepsin L (CTSL), is essential for skin and hair follicle
      homeostasis. Here we examine the effect of CTSL deficiency on hair follicle
      development and cycling in ctsl(-/-) mice by light and electron microscopy,
      Ki67/terminal dUTP nick-end labeling, and trichohyalin immunofluorescence. Hair
      follicle morphogenesis in ctsl(-/-) mice was associated with several
      abnormalities. Defective terminal differentiation of keratinocytes occurred
      during the formation of the hair canal, resulting in disruption of hair shaft
      outgrowth. Both proliferation and apoptosis levels in keratinocytes and
      melanocytes were higher in ctsl(-/-) than in ctsl(+/+) hair follicles. The
      development of the hair follicle pigmentary unit was disrupted by vacuolation of
      differentiating melanocytes. Hair cycling was also abnormal in ctsl(-/-) mice.
      Final stages of hair follicle morphogenesis and the induction of hair follicle
      cycling were retarded. Thereafter, these follicles exhibited a truncated resting
      phase (telogen) and a premature entry into the first growth phase. Further
      abnormalities of telogen development included the defective anchoring of club
      hairs in the skin, which resulted in their abnormal shedding. Melanocyte
      vacuolation was again apparent during the hair cycle-associated reconstruction of
      the hair pigmentary unit. A hallmark of these ctsl(-/-) mice was the severe
      disruption in the exiting of hair shafts to the skin surface. This was mostly
      because of a failure of the inner root sheath (keratinocyte layer next to the
      hair shaft) to fully desquamate. These changes resulted in a massive dilation of
      the hair canal and the abnormal routing of sebaceous gland products to the skin
      surface. In summary, this study suggests novel roles for cathepsin proteases in
      skin, hair, and pigment biology. Principal target tissues that may contain
      protein substrate(s) for this cysteine protease include the developing hair cone,
      inner root sheath, anchoring apparatus of the telogen club, and organelles of
      lysosomal origin (eg, melanosomes).

PMID- 12000733
TI  - CpG island methylation in aberrant crypt foci of the colorectum.
AB  - Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesion in
      colorectal carcinogenesis, and CpG island methylation has been described as an
      important molecular pathway. We therefore studied methylation in ACF from
      patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer.
      We assessed methylation status of the p16 tumor suppressor gene, MINT1
      (methylated in tumor 1), MINT2, MINT31, O(6)-methylguanine-DNA methyltransferase
      gene, and hMLH1 mismatch repair gene. We compared methylation to ACF
      histopathology, K-ras proto-oncogene mutation, loss of heterozygosity at
      chromosome 1p, and microsatellite instability. Methylation was present in 34% (21
      of 61) of ACF, including both FAP and sporadic types, but was more frequent in
      sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially
      dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was
      more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of
      31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K
      ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed,
      but methylation was the only molecular abnormality identified in 16% (10 of 61)
      of ACF. Our findings suggest that methylation in ACF is an early event in the
      pathogenesis of a subset of colorectal carcinomas, and that ACF from FAP patients
      and patients with sporadic colorectal cancer have distinct epigenetic changes
      that reflect differences in molecular pathogenesis.

PMID- 12000734
TI  - Down-regulation of annexin A10 in hepatocellular carcinoma is associated with
      vascular invasion, early recurrence, and poor prognosis in synergy with p53
      mutation.
AB  - Annexins (ANXs) are a large group of calcium-binding proteins participating in
      diverse important biological processes. ANXA10 is the least expressed new member
      of unknown function. We showed that ANXA10 mRNA was expressed in adult liver and
      hepatocellular carcinoma (HCC), but not in multiple adult and fetal tissues,
      cholangiocarcinoma, and several other common carcinomas. Of 182 unifocal primary
      HCCs, ANXA10 mRNA was dramatically reduced in 121 (66%), and the down-regulation
      correlated with p53 mutation (P = 0.024), early intrahepatic tumor recurrence (P
      = 0.0007), and lower 4-year survival (P = 0.0014). Down-regulation of ANXA10 was
      twofold more frequent in large than small HCCs (P = 0.0012), in grade II to III
      than grade I HCC (P < 0.00001), and in stage IIIA to IV than stage I to II HCC (P
      < 0.00001). Moreover, ANXA10 down-regulation and p53 mutation acted
      synergistically toward high-grade (P < 0.00001), high-stage HCC (P < 0.00001),
      and poorer prognosis (P = 0.0025). Our results indicate that the expression of
      the tissue- and tumor-restricted ANXA10 is a marker of liver cell differentiation
      and growth arrest, and its down-regulation associated with malignant phenotype of
      hepatocytes, vascular invasion, and progression of HCC, leading to poor
      prognosis. Thus, ANXA10 might serve as a new potential target of gene therapy for
      HCC.

PMID- 12000735
TI  - Conservation of Epstein-Barr virus cytotoxic T-cell epitopes in posttransplant
      lymphomas: implications for immune therapy.
AB  - Posttransplant lymphoproliferative disease can be treated by the infusion of
      Epstein-Barr virus-specific cytotoxic T lymphocytes, which were raised against
      lymphocytes immortalized with a laboratory strain of Epstein-Barr virus (B95.8).
      Whether the immunodominant epitopes in B95.8 are shared in virus from tumors will
      affect the general applicability of this therapy. We have characterized the viral
      strain and the sequence of commonly recognized cytotoxic T-lymphocyte epitopes in
      25 posttransplant lymphoproliferative disease specimens from 19 patients. Type A
      virus was present in 24 of 25 specimens. No variation in two LMP2A epitopes and a
      few variations mostly outside the targeted epitopes or silent in three EBNA3C
      epitopes were found, with one variation (Arg to Lys) detected in an EBNA3C
      epitope in 12 of 24 tumors. However, cytotoxic T lymphocytes to B95-8-derived
      EBNA3C peptides specifically lysed both B95-8 and the Lys-variant peptide-loaded
      target cells, although with less efficiency. These results suggest that adoptive
      immunotherapy using cytotoxic T lymphocytes expanded with B95.8 stimulators or
      vaccine strategies using B95.8-derived sequence will generally target Epstein
      Barr virus strains present in posttransplant lymphoproliferative disease tumors.

PMID- 12000736
TI  - Differential expression of matrix metalloproteinases 2 and 9 by glial Muller
      cells: response to soluble and extracellular matrix-bound tumor necrosis factor
      alpha.
AB  - Glial Muller cells are known to undergo functional and morphological changes
      during retinal proliferative disorders, but very little is known of the
      contribution of these cells to extracellular matrix deposition during retinal
      wound healing and gliosis. This study constitutes the first demonstration that
      retinal Muller cells express two major matrix metalloproteinases (MMPs),
      gelatinase A (MMP-2) and gelatinase B (MMP-9), implicated in cell migration and
      matrix degradation. Although mRNA and gelatinolytic activity of MMP-2 remained
      unchanged in cultured Muller cells, basal levels of MMP-9 mRNA observed after
      subculture at 24 hours, markedly declined after 48 or 72 hours. This correlated
      with the expression of MMP-9 gelatinolytic activity that peaked at 24 hours, but
      gradually decreased at 48 and 72 hours. Tumor necrosis factor-alpha, in both a
      soluble form or bound to collagen and fibronectin, increased MMP-9 mRNA and
      gelatinolytic activity, but not MMP-2 expression, and its effect could be blocked
      by anti-tumor necrosis factor-alpha antibodies. The results suggest that Muller
      cells may aid in the local control of extracellular matrix deposition during
      retinal proliferative disorders, and that interaction of these cells with matrix
      bound cytokine may influence their pathological behavior. Control of Muller cell
      production of MMP-9 may constitute an important target for the design of new
      therapeutic approaches to treat and prevent retinal proliferative disease.

PMID- 12000737
TI  - Mitochondrial DNA somatic mutations (point mutations and large deletions) and
      mitochondrial DNA variants in human thyroid pathology: a study with emphasis on
      Hurthle cell tumors.
AB  - In an attempt to progress in the understanding of the relationship of
      mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the
      mtDNA in 79 benign and malignant tumors (43 Hurthle and 36 non-Hurthle cell
      neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was
      evaluated by semiquantitative polymerase chain reaction. Somatic point mutations
      and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and
      adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome
      (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations,
      mostly transitions, in 34 tumors and 253 sequence variants in 59 patients.
      Follicular and papillary carcinomas carried a significantly higher prevalence of
      non-silent point mutations of complex I genes than adenomas. We also detected a
      significantly higher prevalence of complex I and complex IV sequence variants in
      the normal parenchyma adjacent to the malignant tumors. Every Hurthle cell tumor
      displayed a relatively high percentage (up to 16%) of mtDNA CD independently of
      the lesion's histotype. The percentage of deleted mtDNA molecules was
      significantly higher in tumors with D-loop mutations than in mtDNA stable tumors.
      Sequence variants of the ATPase 6 gene, one of the complex V genes thought to
      play a role in mtDNA maintenance and integrity in yeast, were significantly more
      prevalent in patients with Hurthle cell tumors than in patients with non-Hurthle
      cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of
      complex I and complex IV genes seem to be involved in thyroid tumorigenesis.
      Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of
      mtDNA CD, the hallmark of Hurthle cell tumors.

PMID- 12000738
TI  - Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of
      sepsis.
AB  - Sepsis and trauma are the two most common causes of disseminated intravascular
      coagulation and multiple organ dysfunction syndrome. Both disseminated
      intravascular coagulation and the systemic inflammatory response syndrome often
      lead to multiple organ dysfunction syndrome. The current studies have evaluated
      the relationship between the anaphylatoxin, C5a, and changes in the
      coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP)
      model of sepsis in rats. CLP animals treated with anti-C5a had a much improved
      number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In
      CLP rats treated with pre-immune IgG there was clearly increased procoagulant
      activity with prolongation of the activated partial thromboplastin time and
      prothrombin time, reduced platelet counts, and increased levels of plasma
      fibrinogen. Evidence for thrombin formation was indicated by early consumption of
      factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin
      and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited
      activation of fibrinolysis was indicated by reduced plasma levels of plasminogen
      and increased levels of tissue plasminogen activator and plasminogen activator
      inhibitor. Most of these parameters were reversed in CLP rats that had been
      treated with anti-C5a. Production of C5a during sepsis may directly or indirectly
      cause hemostatic defects that can be reduced by blockade of C5a.

PMID- 12000739
TI  - Estrogen-related abnormalities in glomerulosclerosis-prone mice: reduced
      mesangial cell estrogen receptor expression and prosclerotic response to
      estrogens.
AB  - The development and progression of glomerulosclerosis (GS) is determined by the
      genetic background. The incidence of end-stage renal disease is increased in
      postmenopausal women, suggesting that estrogen deficiency may play a role in the
      accumulation of extracellular matrix by mesangial cells (MCs), which are
      primarily responsible for the synthesis and degradation of this matrix. Using
      mouse models that are prone or resistant to the development of GS, we compared
      the expression of estrogen receptor (ER)-alpha and ER-beta subtypes in GS-prone
      and GS-resistant glomeruli and isolated MCs, and examined the effects of
      estrogens on ER, collagen, and matrix metalloproteinase (MMP) expression in MCs.
      Glomeruli and MCs from GS-prone mice had decreased expression of ER-alpha and ER
      beta subtypes and ER transcriptional activity was also decreased in their MCs.
      Importantly, although 17 beta-estradiol treatment resulted in decreased collagen
      accumulation and increased MMP-9 expression and activity in MCs from GS-resistant
      mice, there was, paradoxically, no effect on collagen accumulation and decreased
      MMP-9 expression and activity in MCs from GS-prone mice. Thus, GS susceptibility
      is associated with diminished ER expression in MCs. The renal protective effects
      of estrogens, including decreased collagen accumulation and increased MMP-9
      expression, seem to be blunted in GS-prone MCs.

PMID- 12000740
TI  - Caspase-3-Dependent Cleavage of the Glutamate-L-Cysteine Ligase Catalytic Subunit
      during Apoptotic Cell Death.
AB  - Apoptotic cell death is usually accompanied by activation of a family of cysteine
      proteases termed caspases. Caspases mediate the selective proteolysis of multiple
      cellular targets often resulting in the disruption of survival pathways.
      Intracellular levels of the antioxidant glutathione (GSH) are an important
      determinant of cellular susceptibility to apoptosis. The rate-limiting step in
      GSH biosynthesis is mediated by glutamate-L-cysteine ligase (GCL), a
      heterodimeric enzyme consisting of a catalytic (GCLC) and a modifier (GCLM)
      subunit. In this report we demonstrate that GCLC is a direct target for caspase
      mediated cleavage in multiple models of apoptotic cell death. Mutational analysis
      revealed that caspase-mediated cleavage of GCLC occurs at Asp(499) within the
      sequence AVVD(499)G. GCLC cleavage occurs upstream of Cys(553), which is thought
      to be important for association with GCLM. GCLC cleavage is accompanied by a
      rapid loss of intracellular GSH due to caspase-mediated extrusion of GSH from the
      cell. However, while GCLC cleavage is dependent on caspase-3, GSH extrusion
      occurs by a caspase-3-independent mechanism. Our identification of GCLC as a
      target for caspase-3-dependent cleavage during apoptotic cell death suggests that
      this post-translational modification may represent a novel mechanism for
      regulating GSH biosynthesis during apoptosis.

PMID- 12000741
TI  - ADAM 12 protease induces adipogenesis in transgenic mice.
AB  - ADAM 12 (meltrin-alpha) is a member of the ADAM (a disintegrin and
      metalloprotease) family. ADAM 12 functions as an active metalloprotease, supports
      cell adhesion, and has been implicated in myoblast differentiation and fusion.
      Human ADAM 12 exists in two forms: the prototype membrane-anchored protein, ADAM
      12-L, and a shorter secreted form, ADAM 12-S. Here we report the occurrence of
      adipocytes in the skeletal muscle of transgenic mice in which overexpression of
      either form is driven by the muscle creatine kinase promoter. Cells expressing a
      marker of early adipogenesis were apparent in the perivascular space in muscle
      tissue of 1- to 2-week-old transgenic mice whereas mature lipid-laden adipocytes
      were seen at 3 to 4 weeks. Moreover, female transgenics expressing ADAM 12-S
      exhibited increases in body weight, total body fat mass, abdominal fat mass, and
      herniation, but were normoglycemic and did not exhibit increased serum insulin,
      cholesterol, or triglycerides. Male transgenics were slightly overweight and also
      developed herniation but did not become obese. Transgenic mice expressing a
      truncated form of ADAM 12-S lacking the prodomain and the metalloprotease domain
      did not develop this adipogenic phenotype, suggesting a requirement for ADAM 12
      protease activity. This is the first in vivo demonstration that an ADAM protease
      is involved in adipogenesis.

PMID- 12000743
TI  - Deciphering the phosphorylation "code" of the glucocorticoid receptor in vivo.
AB  - The glucocorticoid receptor (GR) is phosphorylated at multiple serine residues in
      a hormone-dependent manner, yet progress on elucidating the function of GR
      phosphorylation has been hindered by the lack of a simple assay to detect
      receptor phosphorylation in vivo. We have produced antibodies that specifically
      recognize phosphorylation sites within human GR at Ser(203) and Ser(211). In the
      absence of hormone, the level of GR phosphorylation at Ser(211) was low compared
      with phosphorylation at Ser(203). Phosphorylation of both residues increased upon
      treatment with the GR agonist dexamethasone. Using a battery of agonists and
      antagonists, we found that the transcriptional activity of GR correlated with the
      amount of phosphorylation at Ser(211), suggesting that Ser(211) phosphorylation
      is a biomarker for activated GR in vivo. Mechanistically, the kinetics of
      Ser(203) and Ser(211) phosphorylation in response to hormone differed, with
      Ser(211) displaying a more robust and sustained phosphorylation relative to
      Ser(203). Analysis of GR immunoprecipitates with phospho-GR-specific antibodies
      indicated that the receptor was phosphorylated heterogeneously at Ser(203) in the
      absence of hormone, whereas in the presence of hormone, a subpopulation of
      receptors was phosphorylated at both Ser(203) and Ser(211). Interestingly,
      biochemical fractionation studies following hormone treatment indicated that the
      Ser(203)-phosphorylated form of the receptor was predominantly cytoplasmic,
      whereas Ser(211)-phosphorylated GR was found in the nucleus. Likewise, by
      immunofluorescence, Ser(203)-phosphorylated GR was located in the cytoplasm and
      perinuclear regions of the cell, but not in the nucleoplasm, whereas strong
      phospho-Ser(211) staining was evident in the nucleoplasm of hormone-treated
      cells. Our results suggest that differentially phosphorylated receptor species
      are located in unique subcellular compartments, likely modulating distinct
      aspects of receptor function.

PMID- 12000744
TI  - Intracellular processing of metalloprotease disintegrin ADAM12.
AB  - ADAM12 has been implicated in cell-cell interactions in myogenesis and cancer,
      but the structure of the mature form of ADAM12 is not known, and its localization
      on the cell surface has been questioned. In this report, we show that full-length
      ADAM12 is N-glycosylated in the endoplasmic reticulum (ER) and proteolytically
      processed in the trans-Golgi network to an approximately 90-kDa form. The
      approximately 90-kDa form, which lacks the prodomain, was the predominant form
      present at the cell surface. Replacement of Leu(73) in the putative alpha-helical
      region in the prodomain with proline resulted in retention of ADAM12 in the ER
      and a complete lack of its processing. However, deletion of the entire pro- and
      metalloprotease domains did not affect the processing and trafficking of ADAM12.
      In contrast, replacement of the cytoplasmic domain of ADAM12 with that of ADAM9
      or adding a c-Myc tag at the C terminus led to a significant increase in
      transport of the protein to the cell surface. These results suggest that the
      cytoplasmic domain of ADAM12 plays an important role in regulating ADAM12 exit
      from the ER. We conclude that properly folded mouse ADAM12, after passing a rate
      limiting step of exit from the ER, is processed in the secretory pathway and
      reaches the cell surface, where it can mediate adhesion-mediated signaling.

PMID- 12000745
TI  - Both N- and C-terminal domains of parathyroid hormone-related protein increase
      interleukin-6 by nuclear factor-kappa B activation in osteoblastic cells.
AB  - Parathyroid hormone (PTH)-related protein (PTHrP) seems to affect bone resorption
      by interaction with bone cytokines, among them interleukin-6 (IL-6). Recent
      studies suggest that nuclear factor (NF)-kappaB activation has an important role
      in bone resorption. We assessed whether the N-terminal fragment of PTHrP, and its
      C-terminal region, unrelated to PTH, can activate NF-kappaB, and its relationship
      with IL-6 gene induction in different rat and human osteoblastic cell
      preparations. Here we present molecular data demonstrating that both PTHrP (1-36)
      and PTHrP (107-139) activate NF-kappaB, leading to an increase in IL-6 mRNA, in
      these cells. Using anti-p65 and anti-p50 antibodies, we detected the presence of
      both proteins in the activated NF-kappaB complex. This effect induced by either
      the N- or C-terminal PTHrP domain in osteoblastic cells appears to occur by
      different intracellular mechanisms, involving protein kinase A or intracellular
      Ca(2+)/protein kinase C activation, respectively. However, the effect of each
      peptide alone did not increase further when added together. Our findings lend
      support to the hypothesis that the C-terminal domain of PTHrP, in a manner
      similar to its N-terminal fragment, might stimulate bone resorption. These
      studies also provide further insights into the putative role of PTHrP as a
      modulator of bone remodeling.

PMID- 12000746
TI  - Activation of protein kinase Czeta is essential for cytokine-induced
      metalloproteinase-1, -3, and -9 secretion from rabbit smooth muscle cells and
      inhibits proliferation.
AB  - Several matrix metalloproteinases (MMPs), including MMP-1, -3, and -9, mediate
      matrix destruction during chronic inflammatory diseases such as arthritis and
      atherosclerosis. MMP up-regulation by inflammatory cytokines involves
      interactions between several transcription factors, including activator protein-1
      and nuclear factor kappaB (NF-kappaB). The upstream regulatory pathways are less
      well understood. We investigated the role of isoforms of protein kinase C (PKC)
      in basic fibroblast growth factor- and interleukin-1alpha-mediated MMP production
      from cultured rabbit aortic smooth muscle cells. A synthetic PKC inhibitor,
      RO318220, inhibited MMP-1, -3, and -9 production by 89 +/- 3, 75 +/- 18, and 89
      +/- 9%, respectively. However, down-regulation of conventional and novel isoforms
      did not inhibit but rather increased MMP-9 production by 48 +/- 16%, implicating
      an atypical PKC isoform. Consistent with this, PKCzeta protein levels and
      activity were stimulated 3.3- and 13-fold, respectively, by basic fibroblast
      growth factor plus interleukin-1alpha and antisense oligonucleotides to PKCzeta
      significantly decreased MMP-9 formation by 62 +/- 18% compared with scrambled
      sequences. Moreover, adenovirus-mediated overexpression of a dominant-negative
      (DN) PKCzeta reduced MMP-1, -3, and -9 production by 78 +/- 9, 76 +/- 8, and 76
      +/- 5%, respectively. DN-PKCzeta inhibited NF-kappaB DNA binding but did not
      affect ERK1/2 activation or AP-1 binding. Antisense PKCzeta oligonucleotides and
      DN-PKCzeta stimulated cell proliferation by 89 +/- 14% (n = 4) and 305 +/- 74% (n
      = 3), respectively (both p < 0.05). Our results show that PKCzeta is essential
      for cytokine-induced up-regulation of MMP-1, -3, and -9, most likely by
      activating NF-kappaB. Selective inhibition of PKCzeta is therefore a possible
      strategy to inhibit MMP production in inflammatory diseases such as
      atherosclerosis.

PMID- 12000747
TI  - Calcyclin is an early vasopressin-induced gene in the renal collecting duct. Role
      in the long term regulation of ion transport.
AB  - Long-term effects of arginine vasopressin (AVP) in the kidney involve the
      transcription of unidentified genes. By subtractive hybridization experiments
      performed on the RCCD(1) cortical collecting duct cell line, we identified
      calcyclin as an early AVP-induced gene (1 h). Calcyclin is a calcium-binding
      protein involved in the transduction of intracellular signals. In the kidney,
      calcyclin was localized at the mRNA level in the glomerulus, all along the
      collecting duct, and in the epithelium lining the papilla. In RCCD(1) cells and
      in m-IMCD(3) inner medullary collecting duct cells, calcyclin was evidenced in
      the cytoplasm. Calcyclin mRNA levels were progressively increased by AVP
      treatment in RCCD(1) (1.7-fold at 4 h) and m-IMCD(3) (2-fold at 7.5 h) cells. In
      RCCD(1) cells, calcyclin protein levels were increased by 4 h of AVP treatment.
      In vivo, treatment of genetically vasopressin-deficient Brattleboro rats with AVP
      for 4 days induced an increase in both calcyclin and aquaporin-2 mRNA expression.
      Finally, introduction of anti-calcyclin antibodies into RCCD(1) cells by
      permeabilizing the plasma membrane prevented the long-term (but not short-term)
      increase in short-circuit current induced by AVP. Taken together, these results
      suggest that calcyclin is an early vasopressin-induced gene that participates in
      the late phase of the hormone response in transepithelial ion transport.

PMID- 12000748
TI  - Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear
      translocation and activation of constitutive androstane receptor in vivo.
AB  - Phenobarbital (PB) induction of CYP2B genes is mediated by translocation of the
      constitutively active androstane receptor (CAR) to the nucleus. Interaction of
      CAR with p160 coactivators and enhancement of CAR transactivation by the
      coactivators have been shown in cultured cells. In the present studies, the
      interaction of CAR with the p160 coactivator glucocorticoid receptor-interacting
      protein 1 (GRIP1) was examined in vitro and in vivo. Binding of GRIP1 to CAR was
      shown by glutathione S-transferase (GST) pull-down and affinity DNA binding. N-
      or C-terminal fragments of GRIP1 that contained the central receptor-interacting
      domain bound to GST-CAR, but the presence of ligand increased the binding to GST
      CAR of only the fragments containing the C-terminal region. In gel shift
      analysis, binding to CAR was observed only with GRIP1 fragments containing the C
      terminal region, and the binding was increased by a CAR agonist and decreased by
      a CAR antagonist. Expression of GRIP1 enhanced CAR-mediated transactivation in
      cultured hepatic-derived cells 2-3-fold. In hepatocytes transfected in vivo,
      expression of exogenous GRIP1 alone induced transactivation of the CYP2B1 PB
      dependent enhancer 15-fold, whereas CAR expression alone resulted in only a 3
      fold enhancement in untreated mice. Remarkably, CAR and GRIP1 together
      synergistically transactivated the enhancer about 150-fold, which is
      approximately equal to activation by PB treatment. In PB-treated mice, expression
      of exogenous CAR alone had little effect, expression of GRIP1 increased
      transactivation about 2-fold, and with CAR and GRIP, a 4-fold activation was
      observed. In untreated mice, expression of GRIP resulted in nuclear translocation
      of green fluorescent protein-CAR. These results strongly suggest that a p160
      coactivator functions in CAR-mediated transactivation in vivo in response to PB
      treatment and that the synergistic activation of CAR by GRIP in untreated animals
      results from both nuclear translocation and activation of CAR.

PMID- 12000749
TI  - The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor
      gene p14ARF via a variant T-site in the initiator.
AB  - The murine tumor suppressor p19(ARF) (p14(ARF) in humans) is thought to fulfill
      an important protective role in preventing primary cells from oncogenic
      transformation via its action in the p53 pathway. Several disease-implicated
      regulators of p19(ARF) are known to date, among which are the T-box genes TBX2,
      which resides on an amplicon in primary breast tumors, and TBX3, which is mutated
      in the human developmental disorder Ulnar-Mammary syndrome. Here we identify a
      variant T-site, matching 13 of 20 nucleotides of a consensus T-site, as the
      essential TBX2/TBX3-binding element in the human p14(ARF) promoter. Mutant
      analysis indicates that both the consensus T-box and a C-terminal conserved
      repression domain are essential for p14(ARF) repression. Whereas the core
      nucleotides required for interaction of the archetypal T-box protein Brachyury
      with a consensus T-site are conserved in the variant site, additional flanking
      nucleotides contribute to the specificity of TBX2 binding. This is illustrated by
      the inability of TBX1A or Xbra to activate via the variant p14(ARF) T-site.
      Importantly, this suggests a hitherto unsuspected level of specificity associated
      with T-box factors and corresponding recognition sites in regulating their target
      genes in vivo.

PMID- 12000750
TI  - Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein
      kinase-1 activity in the human colon cancer HT-29 cell line.
AB  - Nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase (COX)
      activity, are powerful antineoplastic agents that exert their antiproliferative
      and proapoptotic effects on cancer cells by COX-dependent and/or COX-independent
      pathways. Celecoxib, a COX-2-specific inhibitor, has been shown to reduce the
      number of adenomatous colorectal polyps in patients with familial adenomatous
      polyposis. Here, we show that celecoxib induces apoptosis in the colon cancer
      cell line HT-29 by inhibiting the 3-phosphoinositide-dependent kinase 1 (PDK1)
      activity. This effect was correlated with inhibition of the phosphorylation of
      the PDK1 downstream substrate Akt/protein kinase B (PKB) on two regulatory sites,
      Thr(308) and Ser(473). However, expression of a constitutive active form of
      Akt/PKB (myristoylated PKB) has a low protective effect toward celecoxib-induced
      cell death. In contrast, overexpression of constitutive active mutant of PDK1
      (PDK1(A280V)) was as potent as the pancaspase inhibitor, benzyloxycarbonyl-Val
      Ala-Asp-fluoromethylketone, to impair celecoxib-induced apoptosis. By contrast,
      cells expressing a kinase-defective mutant of PDK1 (PDK1(K114G)) remained
      sensitive to celecoxib. Furthermore, in vitro measurement reveals that celecoxib
      was a potential inhibitor of PDK1 activity with an IC(50) = 3.5 microm. These
      data indicate that inhibition of PDK1 signaling is involved in the proapoptotic
      effect of celecoxib in HT-29 cells.

PMID- 12000751
TI  - Regulation of retinoic acid receptor alpha by protein kinase C in B16 mouse
      melanoma cells.
AB  - We have previously found that retinoic acid stimulates the expression of protein
      kinase C alpha (PKC) in B16 mouse melanoma cells. Because it has been reported
      that PKC can phosphorylate retinoic acid receptor (RAR) and alter its function,
      we determined whether changes in the level and/or activity of PKC could affect
      the expression or function of the RAR in B16 melanoma. Using in vivo
      phosphorylation and band shift techniques, we could not demonstrate that altering
      PKC activity and/or protein level changed the in vivo phosphorylation of RAR
      alpha. However activation of PKC resulted in increased RAR alpha protein.
      Increased receptor protein correlated with a phorbol dibutyrate-stimulated
      increase in receptor activation function-2 (AF-2)-dependent transcriptional
      activity. Use of enzyme inhibitors and dominant-negative PKCs indicated that
      enzyme activity was required for elevation in the RAR alpha. The PKC-mediated
      increase in RAR alpha was due to a 2.5-fold increase in the half-life of this
      protein. In contrast, the down-regulation of PKC diminished RAR alpha protein
      half-life and markedly inhibited AF-2-dependent transcriptional activity. The
      down-regulation of PKC also inhibited the binding of RAR to a retinoic acid
      response element and the retinoic acid induction of RAR beta expression. These
      findings suggest that PKC can influence retinoic acid signaling by altering the
      stability of RAR protein without directly phosphorylating this receptor.

PMID- 12000752
TI  - Activation of the phosphatidylinositol 3-kinase/Akt signaling pathway by retinoic
      acid is required for neural differentiation of SH-SY5Y human neuroblastoma cells.
AB  - Retinoic acid (RA) induces neural differentiation of SH-SY5Y neuroblastoma cells.
      We show that the mRNA levels of the differentiation-inhibiting basic helix-loop
      helix transcription factors ID1, ID2, and ID3 are down-regulated during RA
      induced differentiation of SH-SY5Y cells. The levels of ID proteins decreased in
      parallel to the observed transcriptional repression. The expression of other
      basic helix-loop-helix genes changed during RA-induced differentiation:
      expression of neuroblast-specific ASCL1 (HASH-1) gene was promptly reduced after
      RA treatment, whereas expression of differentiation-promoting genes NEUROD6 (NEX
      1, HATH-2) and NEUROD1 was increased. Treatments with 12-O-tetradecanoylphorbol
      13-acetate, another inducer of neuroblastoma cell differentiation, also resulted
      in coordinated down-regulation of ID gene expression, underscoring the role of ID
      genes in differentiation. Down-regulation of ID gene expression by RA involves a
      complex mechanism because full transcriptional repression required newly
      synthesized proteins and signaling by phosphatidylinositol 3-kinase (PI3K). RA
      treatment activates the PI3K/Akt signaling pathway, resulting in increased PI3K
      activity in extracts from RA-treated cells and a rapid increase in
      phosphorylation of Akt in Ser-473. Inhibition of PI3K by LY294002 impaired RA
      induced differentiation, as assessed by morphological and biochemical criteria.
      We propose that RA, by activating the PI3K/Akt signaling pathway, plays an
      important role in the regulation of neuronal cell survival.

PMID- 12000753
TI  - Mode of action of pectin lyase A of Aspergillus niger on differently C(6)
      substituted oligogalacturonides.
AB  - A thorough investigation of the mode of action of Aspergillus niger (4M-147)
      pectin lyase A (PLA) on differently C(6)-substituted oligogalacturonides is
      described. PLA appeared to be very specific for fully methyl-esterified
      oligogalacturonides: removal of the methyl-ester or changing the type of ester
      (ethyl esterification) or transamidation resulted in (almost) complete loss of
      conversion. The PLA activity increased with increasing length of the substrate up
      to a degree of polymerization (DP) of 8 indicating the presence of at least eight
      subsites on the enzyme. Product analysis demonstrated the formation of several
      Delta 4,5 unsaturated products and their saturated counterparts. The Delta 4,5
      unsaturated trimer was the main product up to DP 8. For DP 9 and 10 Delta 4,5
      unsaturated tetramer was the major product. Based upon the bond cleavage
      frequencies, a provisional subsite map was calculated, which supports the
      presence of eight subsites. By limited alkaline de-esterification of fully methyl
      esterified pentamer and hexamer two sets of partially methyl-esterified pentamers
      (x and y methyl groups) and hexamers (a and b methyl groups) were prepared.
      Matrix-assisted laser desorption/ionization time of flight mass spectroscopy
      (MALDI-TOF MS) analysis demonstrated that the methyl-ester distribution was fully
      random. Using these partially methyl-esterified oligogalacturonides as substrates
      for PLA a 10-fold decrease in reaction rate was recorded compared with the fully
      methyl-esterified counterparts. Analysis of the methyl-ester distribution of the
      products showed that PLA tolerates carboxyl groups in the substrate binding
      cleft. At either subsite +2, +4, or -1 to -4 a free carboxyl group could be
      tolerated, whereas methyl-esters were obligatory at subsite +1 and +3. So PLA is
      capable to cleave the bond between a methyl-esterified and a non-esterified
      galacturonic acid residue, where the newly formed Delta 4,5 unsaturated non
      reducing end residue always contains a methyl-ester.

PMID- 12000754
TI  - Identification of a region within the ErbB2/HER2 intracellular domain that is
      necessary for ligand-independent association.
AB  - Ligand-independent ErbB2 activation occurs principally by two distinct
      mechanisms: overexpression and mutation. Overexpression of ErbB2 at the plasma
      membrane drives receptor self-association in a concentration-dependent manner,
      which in turn leads to constitutive receptor activation. Subsets of human breast
      cancers contain a molecular alteration that leads to erbB2 gene amplification and
      subsequent protein overexpression. Although not recognized to occur in human
      cancers, mutation can also lead to increased ErbB2 association. A well
      characterized mutant of the rodent ortholog neu involves substitution of
      glutamate for valine within the transmembrane domain. In each case, a number of
      explanations have been proposed to explain the resulting ErbB2 activation. These
      include stabilization of receptor oligomers, release of negative constraints, and
      altered receptor conformations. Here we define a short amino acid segment
      comprising amino acids 966-968 in the intracellular domain that seemingly
      disrupts receptor-receptor association that is driven either by overexpression or
      mutation in the transmembrane region. Because of the hydrophobic nature of these
      amino acids (VVI), we propose that alteration of this segment likely results in a
      global conformational change in an area that has been proposed previously to be a
      dimerization motif for ErbB homomeric association.

PMID- 12000755
TI  - Predominant nuclear localization of mammalian target of rapamycin in normal and
      malignant cells in culture.
AB  - Mammalian target of rapamycin (mTOR) controls initiation of translation through
      regulation of ribosomal p70S6 kinase (S6K1) and eukaryotic translation initiation
      factor-4E (eIF4E) binding protein (4E-BP). mTOR is considered to be located
      predominantly in cytosolic or membrane fractions and may shuttle between the
      cytoplasm and nucleus. In most previous studies a single cell line, E1A
      immortalized human embryonic kidney cells (HEK293), has been used. Here we show
      that in human malignant cell lines, human fibroblasts, and murine myoblasts mTOR
      is predominantly nuclear. In contrast, mTOR is largely excluded from the nucleus
      in HEK293 cells. Hybrids between HEK293 and Rh30 rhabdomyosarcoma cells generated
      cells co-expressing markers unique to HEK293 (E1A) and Rh30 (MyoD). mTOR
      distribution was mainly nuclear with detectable levels in the cytoplasm. mTOR
      isolated from Rh30 nuclei phosphorylated recombinant GST-4E-BP1 (Thr-46) in vitro
      and thus has kinase activity. We next investigated the cellular distribution of
      mTOR substrates 4E-BP, S6K1, and eIF4E. 4E-BP was exclusively detected in
      cytoplasmic fractions in all cell lines. S6K1 was localized in the cytoplasm in
      colon carcinoma, HEK293 cells, and IMR90 fibroblasts. S6K1 was readily detected
      in all cellular fractions derived from rhabdomyosarcoma cells. eIF4E was detected
      in all fractions derived from rhabdomyosarcoma cells but was not detectable in
      nuclear fractions from colon carcinoma HEK293 or IMR90 cells.

PMID- 12000756
TI  - The cathepsin B of Toxoplasma gondii, toxopain-1, is critical for parasite
      invasion and rhoptry protein processing.
AB  - Cysteine proteinases play a major role in invasion and intracellular survival of
      a number of pathogenic parasites. We cloned a single copy gene, tgcp1, from
      Toxoplasma gondii and refolded recombinant enzyme to yield active proteinase.
      Substrate specificity of the enzyme and homology modeling identified the
      proteinase as a cathepsin B. Specific cysteine proteinase inhibitors interrupted
      invasion by tachyzoites. The T. gondii cathepsin B localized to rhoptries,
      secretory organelles required for parasite invasion into cells. Processing of the
      pro-rhoptry protein 2 to mature rhoptry proteins was delayed by incubation of
      extracellular parasites with a cathepsin B inhibitor prior to pulse-chase
      immunoprecipitation. Delivery of cathepsin B to mature rhoptries was impaired in
      organisms with disruptions in rhoptry formation by expression of a dominant
      negative micro1-adaptin. Similar disruption of rhoptry formation was observed
      when infected fibroblasts were treated with a specific inhibitor of cathepsin B,
      generating small and poorly developed rhoptries. This first evidence for
      localization of a cysteine proteinase to the unusual rhoptry secretory organelle
      of an apicomplexan parasite suggests that the rhoptries may be a prototype of a
      lysosome-related organelle and provides a critical link between cysteine
      proteinases and parasite invasion for this class of organism.

PMID- 12000757
TI  - Dependence of selective gene activation on the androgen receptor NH2- and COOH
      terminal interaction.
AB  - The agonist-induced androgen receptor NH(2)- and COOH-terminal (N/C) interaction
      is mediated by the FXXLF and WXXLF NH(2)-terminal motifs. Here we demonstrate
      that agonist-dependent transactivation of prostate-specific antigen (PSA) and
      probasin enhancer/promoter regions requires the N/C interaction, whereas the sex
      limited protein gene and mouse mammary tumor virus long terminal repeat do not.
      Transactivation of PSA and probasin response regions also depends on activation
      function 1 (AF1) in the NH(2)-terminal region but can be increased by binding an
      overexpressed p160 coactivator to activation function 2 (AF2) in the ligand
      binding domain. The dependence of the PSA and probasin enhancer/promoters on the
      N/C interaction for transactivation allowed us to demonstrate that in the
      presence of androgen, the WXXLF motif with the sequence (433)WHTLF(437)
      contributes as an inhibitor to AR transactivation. We further show that like the
      FXXLF and LXXLL motifs, the WXXLF motif interacts in the presence of androgen
      with AF2 in the ligand binding domain. Sequence comparisons among species
      indicate greater conservation of the FXXLF motif compared with the WXXLF motif,
      paralleling the functional significance of these binding motifs. The data provide
      evidence for promoter-specific differences in the requirement for the androgen
      receptor N/C interaction and in the contributions of AF1 and AF2 in androgen
      induced gene regulation.

PMID- 12000758
TI  - Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation
      profiles of endogenous breast cancer mucin. High density and prevalent core 2
      based glycosylation.
AB  - Knowledge about the O-linked glycan chains of tumor-associated MUC1 is primarily
      based on enzymatic and immunochemical evidence. To obtain structural information
      and to overcome limitations by the scarcity of endogenous mucin, we expressed a
      recombinant glycosylation probe corresponding to six MUC1 tandem repeats in four
      breast cancer cell lines. Comparative analyses of the O-glycan profiles were
      performed after hydrazinolysis and normal phase chromatography of 2
      aminobenzamide-labeled glycans. Except for a general reduction in the O-glycan
      chain lengths and a high density glycosylation, no common structural pattern was
      revealed. T47D fusion protein exhibits an almost complete shift from core 2 to
      core 1 expression with a preponderance of sialylated glycans. By contrast, MCF-7,
      MDA-MB231, and ZR75-1 cells glycosylate the MUC1 repeat peptide preferentially
      with core 2-based glycans terminating mostly with alpha 3-linked sialic acid (MDA
      MB231, ZR75-1) or alpha 2/3-linked fucose (MCF-7). Endogenous MUC1 from T47D and
      MCF-7 cell supernatants revealed almost identical O-glycosylation profiles
      compared with the respective recombinant probes, indicating that the fusion
      proteins reflected the authentic O-glycan profiles of the cells. The structural
      patterns in the majority of cells under study are in conflict with biosynthetic
      models of MUC1 O-glycosylation in breast cancer, which claim that the truncation
      of normal core 2-based polylactosamine structures to short sialylated core 1
      based glycans is due to the reduced activity of core 2-forming beta 6-N
      acetylglucosaminyltransferases and/or to overexpression of competitive alpha 3-
      sialyltransferase.

PMID- 12000759
TI  - Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family
      members.
AB  - Ubiquitous calpains (mu- and m-calpain) have been repeatedly implicated in
      apoptosis, but the underlying mechanism(s) remain(s) to be elucidated. We
      examined ionomycin-induced cell death in LCLC 103H cells, derived from a human
      large cell lung carcinoma. We detected hallmarks of apoptosis such as membrane
      blebbing, nuclear condensation, DNA ladder formation, caspase activation, and
      poly-(ADP-ribose)polymerase cleavage. Apoptosis was prevented by preincubation of
      the cells with the calpain inhibitor acetyl-calpastatin 27-peptide and the
      caspase inhibitor Z-DEVD-fmk, implicating both the calpains and caspases in the
      apoptotic process. The apoptotic events correlated in a calpastatin-inhibitable
      manner with Bid and Bcl-2 decrease and with activation of caspases-9, -3, and -7.
      In vitro both ubiquitous calpains cleaved recombinant Bcl-2, Bid, and Bcl-x(L) at
      single sites truncating their N-terminal regions. Binding studies revealed
      diminished interactions of calpain-truncated Bcl-2 and Bid with immobilized
      intact Bcl-2 family proteins. Moreover, calpain-cleaved Bcl-2 and Bid induced
      cytochrome c release from isolated mitochondria. We conclude that ionomycin
      induced calpain activation promotes decrease of Bcl-2 proteins thereby triggering
      the intrinsic apoptotic pathway.

PMID- 12000760
TI  - Apolipoprotein A-I is necessary for the in vivo formation of high density
      lipoprotein competent for scavenger receptor BI-mediated cholesteryl ester
      selective uptake.
AB  - The severe depletion of cholesteryl ester (CE) in steroidogenic cells of apoA-I(
      /-) mice suggests that apolipoprotein (apo) A-I plays a specific role in the high
      density lipoprotein (HDL) CE-selective uptake process mediated by scavenger
      receptor BI (SR-BI) in vivo. The nature of this role, however, is unclear because
      a variety of apolipoproteins bind to SR-BI expressed in transfected cells. In
      this study the role of apoA-I in SR-BI-mediated HDL CE-selective uptake was
      tested via analyses of the biochemical properties of apoA-I(-/-) HDL and its
      interaction with SR-BI on adrenocortical cells, hepatoma cells, and cells
      expressing a transfected SR-BI. apoA-I(-/-) HDL are large heterogeneous particles
      with a core consisting predominantly of CE and a surface enriched in
      phospholipid, free cholesterol, apoA-II, and apoE. Functional analysis showed
      apoA-I(-/-) HDL to bind to SR-BI with the same or higher affinity as compared
      with apoA-I(+/+) HDL, but apoA-I(-/-) HDL showed a 2-3-fold decrease in the
      V(max) for CE transfer from the HDL particle to adrenal cells. These results
      indicate that the absence of apoA-I results in HDL particles with a reduced
      capacity for SR-BI-mediated CE-selective uptake. The reduced V(max) illustrates
      that HDL properties necessary for binding to SR-BI are distinct from those
      properties necessary for the transfer of HDL CE from the core of the HDL particle
      to the plasma membrane. The reduced V(max) for HDL CE-selective uptake likely
      contributes to the severe reduction in CE accumulation in steroidogenic cells of
      apoA-I(-/-) mice.

PMID- 12000761
TI  - Functional analysis of cathepsin B-like cysteine proteases from Leishmania
      donovani complex. Evidence for the activation of latent transforming growth
      factor beta.
AB  - Cathepsin B-like genes from Leishmania donovani and Leishmania chagasi have been
      isolated and characterized. It is a single gene, which is constitutively
      expressed in all the life cycle stages of the parasite. Studies using cathepsin B
      specific inhibitor treatment suggested that cathepsin B does not seem to play a
      role in the promastigote stages of the parasite, however it aids in the parasite
      survival within the host macrophages. Antisense mRNA inhibition of cathepsin B
      gene also revealed that it plays an important role in the parasite survival
      within the host macrophages. Furthermore, for the first time, we have shown that
      Leishmania whole cell lysates as well as the recombinant cathepsin B protein
      cleaved human recombinant latent transforming growth factor (TGF)-beta1 into a
      mature peptide releasing the latency associated protein, in a cell-free
      incubation system. Mink lung epithelial cell growth inhibition assay revealed
      that the cleaved TGF-beta1 was biologically active, suggesting that Leishmania
      cathepsin B can cleave latent TGF-beta1 into mature and active form. These
      results suggest that cathepsin B plays an important role in Leishmania survival
      within the host macrophages by activating latent TGF-beta1.

PMID- 12000762
TI  - The role of cadherin, beta-catenin, and AP-1 in retinoid-regulated carcinoma cell
      differentiation and proliferation.
AB  - Vitamin A derivatives (retinoids) are potent regulators of cell proliferation and
      differentiation. Retinoids inhibit the function of the oncogenic AP-1 and beta
      catenin/TCF pathways and also stabilize components of the adherens junction, a
      tumor suppressor complex. When treated with retinoic acid (RA), the breast cancer
      cell line, SKBR3, undergoes differentiation and reduction in cell proliferation.
      The present work demonstrates that in SKBR3 cells, which exhibit high AP-1
      activity, RA-regulation of cadherin expression and function, but not changes in
      AP-1 (or beta-catenin/TCF) signaling, is responsible for the epithelial
      differentiation. However, cadherin function and recruitment of beta-catenin to
      the membrane is not required for RA to regulate DNA synthesis in these cells. RA
      also reduces the activity of an AP-1 and TCF-sensitive cyclin D1 reporter in
      SKBR3 cells in a manner that is independent of the TCF site. In contrast, in
      SW480 cells, which have high levels of beta-catenin/TCF signaling, the activity
      and retinoid responsiveness of the cyclin D1 promoter was markedly inhibited by
      mutation of the TCF site. These data indicate that the remarkably broad effects
      of RA on the growth and differentiation of many different epithelial cancers may
      well be explained by the ability of RA to differentially regulate the activity of
      RAR/RXR, AP-1, and beta-catenin/TCF pathways.

PMID- 12000763
TI  - Cell cycle-dependent subcellular localization of exchange factor directly
      activated by cAMP.
AB  - Epac belongs to a new family of proteins that can directly mediate the action of
      the intracellular second messenger cAMP by activating a downstream small GTPase
      Rap1. The Epac/Rap1 pathway represents a novel cAMP-signaling cascade that is
      independent of the cAMP-dependent protein kinase (PKA). In this study, we have
      used fluorescence microscopy to probe the intracellular targeting of Epac during
      different stages of the cell division cycle and the structural features that are
      important for Epac localization. Our results suggest Epac, endogenous or
      expressed as a green fluorescent protein fusion protein, is mainly localized to
      the nuclear membrane and mitochondria during interphase in COS-7 cells. Deletion
      mutagenesis analysis reveals that whereas the DEP domain is responsible for
      membrane association, the mitochondrial-targeting sequence is located at the N
      terminus. Although Epac predominantly exhibits perinuclear localization in
      interphase, the subcellular localization of Epac is cell cycle-dependent. Epac
      disassociates from the nuclear membrane and localizes to the mitotic spindle and
      centrosomes in metaphase. At the end of the cell cycle, Epac is observed to
      reassociate with the nuclear envelope and concentrate around the contractile
      ring. Furthermore, overexpression of Epac in COS-7 cells leads to an increase in
      multinuclear cell populations. These results suggest that Epac may play an
      important role in mitosis.

PMID- 12000764
TI  - Targeted disruption of spermidine/spermine N1-acetyltransferase gene in mouse
      embryonic stem cells. Effects on polyamine homeostasis and sensitivity to
      polyamine analogues.
AB  - We have generated mouse embryonic stem cells with targeted disruption of
      spermidine/spermine N(1)-acetyltransferase (SSAT) gene. The targeted cells did
      not contain any inducible SSAT activity, and the SSAT protein was not present.
      The SSAT-deficient cells proliferated normally and appeared to maintain otherwise
      similar polyamine pools as did the wild-type cells, with the possible exception
      of constantly elevated (about 30%) cellular spermidine. As expected, the mutated
      cells were significantly more resistant toward the growth-inhibitory action of
      polyamine analogues, such as N(1),N(11)-diethylnorspermine. However, this
      resistance was not directly attributable to cellular depletion of the higher
      polyamines spermidine and spermine, as the analogue depleted the polyamine pools
      almost equally effectively in both wild-type and SSAT-deficient cells. Tracer
      experiments with [C(14)]-labeled spermidine revealed that SSAT activity is
      essential for the back-conversion of spermidine to putrescine as radioactive N(1)
      acetylspermidine and putrescine were readily detectable in N(1),N(11)
      diethylnorspermine-exposed wild-type cells but not in SSAT-deficient cells.
      Similar experiments with [C(14)]spermine indicated that the latter polyamine was
      converted to spermidine in both cell lines and, unexpectedly, more effectively in
      the targeted cells than in the parental cells. This back-conversion was only
      partly inhibited by MDL72527, an inhibitor of polyamine oxidase. These results
      indicated that SSAT does not play a major role in the maintenance of polyamine
      homeostasis, and the toxicity exerted by polyamine analogues is largely not based
      on SSAT-induced depletion of the natural polyamines. Moreover, embryonic stem
      cells appear to operate an SSAT-independent system for the back-conversion of
      spermine to spermidine.

PMID- 12000765
TI  - A role for CCAAT/enhancer-binding protein in hepatic expression of thrombin
      activable fibrinolysis inhibitor.
AB  - Thrombin-activable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase B-like
      zymogen that upon activation by thrombin, thrombin-thrombomodulin, or plasmin
      attenuates fibrin clot lysis by inhibiting positive feedback in the fibrinolytic
      cascade. The concentration of TAFI in plasma varies in the human population and
      thus may constitute a risk factor for thrombotic disorders. In addition, TAFI has
      been reported to be a positive acute phase reactant in mice. We have initiated
      molecular analysis of the human TAFI promoter to understand the mechanisms
      underlying regulation of TAFI gene expression. We identified a putative C/EBP
      binding site between -53 and -40 of the promoter. Mutations in this site that
      abolish C/EBP binding decrease TAFI promoter activity in human hepatoma (HepG2)
      cells by approximately 80%. Gel mobility shift analyses indicated that C/EBP-beta
      present in HepG2 nuclear extracts and C/EBP-alpha and -beta present in adult rat
      liver nuclear extracts bind to the C/EBP site. C/EBP-alpha, -beta, and -delta
      isoforms are all capable of binding to the C/EBP site and activating the TAFI
      promoter. The identification of a functional C/EBP-binding site in the human TAFI
      promoter may have important implications for the regulation of expression of this
      gene during development and in response to inflammatory stimuli.

PMID- 12000766
TI  - All four members of the Ten-m/Odz family of transmembrane proteins form dimers.
AB  - Ten-m/Odz/teneurins are a new family of four distinct type II transmembrane
      molecules. Their extracellular domains are composed of an array of eight
      consecutive EGF modules followed by a large globular domain. Two of the eight
      modules contain only 5 instead of the typical 6 cysteine residues and have the
      capability to dimerize in a covalent, disulfide-linked fashion. The structural
      properties of the extracellular domains of all four mouse Ten-m proteins have
      been analyzed using secreted, recombinant molecules produced by mammalian HEK-293
      cells. Electron microscopic analysis supported by analytical ultracentrifugation
      data revealed that the recombinant extracellular domains of all Ten-m proteins
      formed homodimers. SDS-PAGE analysis under nonreducing conditions as well as
      negative staining after partial denaturation of the molecules indicated that the
      globular COOH-terminal domains of Ten-m1 and -m4 contained subdomains with a
      pronounced stability against denaturing agents, especially when compared with the
      homologous domains of Ten-m2 and -m3. Cotransfection experiments of mammalian
      cells with two different extracellular domains revealed that Ten-m molecules have
      also the ability to form heterodimers, a property that, combined with alternative
      splicing events, allows the formation of a multitude of molecules with different
      characteristics from a limited set of genes.

PMID- 12000767
TI  - tau Exon 10 expression involves a bipartite intron 10 regulatory sequence and
      weak 5' and 3' splice sites.
AB  - tau mutations that deregulate alternative exon 10 (E10) splicing cause
      frontotemporal dementia with parkinsonism chromosome 17-type by several
      mechanisms. Previously we showed that E10 splicing involved exon splicing
      enhancer sequences at the 5' and 3' ends of E10, an exon splicing silencer, a
      weak 5' splice site, and an intron splicing silencer (ISS) within intron 10
      (I10). Here, we identify additional regulatory sequences in I10 using both non
      neuronal and neuronal cells. The ISS sequence extends from I10 nucleotides 11-18,
      which is sufficient to inhibit use of a weakened 5' splice site of a heterologous
      exon. Furthermore, ISS function is location-independent but requires proximity to
      a weak 5' splice site. Thus, the ISS functions as a linear sequence. A new cis
      acting element, the intron splicing modulator (ISM), was identified immediately
      downstream of the ISS at I10 positions 19-26. The ISM and ISS form a bipartite
      regulatory element, within which the ISM functions when the ISS is present,
      mitigating E10 repression by the ISS. Additionally, the 3' splice site of E10 is
      weak and requires exon splicing enhancer elements for efficient E10 inclusion.
      Thus far, tau FTDP-17 splicing mutations affect six predicted cis-regulatory
      sequences.

PMID- 12000768
TI  - Transbilayer movement of dipalmitoylphosphatidylcholine in proteoliposomes
      reconstituted from detergent extracts of endoplasmic reticulum. Kinetics of
      transbilayer transport mediated by a single flippase and identification of
      protein fractions enriched in flippase activity.
AB  - Phospholipid translocation (flip-flop) across membrane bilayers is typically
      assessed via assays utilizing partially water-soluble phospholipid analogs as
      transport reporters. These assays have been used in previous work to show that
      phospholipid translocation in biogenic (self-synthesizing) membranes such as the
      endoplasmic reticulum is facilitated by specific membrane proteins (flippases).
      To extend these studies to natural phospholipids while providing a framework to
      guide the purification of a flippase, we now describe an assay to measure the
      transbilayer translocation of dipalmitoylphosphatidylcholine, a membrane-embedded
      phospholipid, in proteoliposomes generated from detergent-solubilized rat liver
      endoplasmic reticulum. Translocation was assayed using phospholipase A(2) under
      conditions where the vesicles were determined to be intact. Phospholipase A(2)
      rapidly hydrolyzed phospholipids in the outer leaflet of liposomes and
      proteoliposomes with a half-time of approximately 0.1 min. However, for flippase
      containing proteoliposomes, the initial rapid hydrolysis phase was followed by a
      slower phase reflecting flippase-mediated translocation of phospholipids from the
      inner to the outer leaflet. The amplitude of the slow phase was decreased in
      trypsin-treated proteoliposomes. The kinetic characteristics of the slow phase
      were used to assess the rate of transbilayer equilibration of phospholipids. For
      250-nm diameter vesicles containing a single flippase, the half-time was 3.3 min.
      Proportionate reductions in equilibration half-time were observed for
      preparations with a higher average number of flippases/vesicle. Preliminary
      purification steps indicated that flippase activity could be enriched
      approximately 15-fold by sequential adsorption of the detergent extract onto
      anion and cation exchange resins.

PMID- 12000769
TI  - Deregulated MAPK activity prevents adipocyte differentiation of fibroblasts
      lacking the retinoblastoma protein.
AB  - A functional retinoblastoma protein (pRB) is required for adipose conversion of
      preadipocyte cell lines and primary mouse embryo fibroblasts (MEFs) in response
      to treatment with standard adipogenic inducers. Interestingly, lack of functional
      pRB in MEFs was recently linked to elevated Ras activity. Ras-dependent signaling
      plays a significant, although incompletely understood, role in adipocyte
      differentiation, because activated Ras has been reported to either promote or
      inhibit adipogenesis depending on the cellular context. In various cell types
      activation of Ras leads to activation of the mitogen-activated protein kinases
      (MAPKs), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B
      (PKB)/Akt, which exert opposing effects on adipogenesis, with ERK1/2 inhibiting
      and PKB/Akt promoting terminal differentiation. Here we report that the levels of
      activated ERK1/2 and PKB/Akt are significantly increased in pRB-deficient MEFs
      both before and after the addition of adipogenic inducers. Consistently, we
      detected higher levels of activated Ras in MEFs lacking pRB. Suppression of
      ERK1/2 activation by the MEK inhibitor UO126 restored the ability of pRB
      deficient MEFs to undergo adipocyte differentiation, as manifested by expression
      of adipocyte marker genes and lipid accumulation. Furthermore and reflecting the
      elevated levels of activated PKB/Akt in the pRB-deficient MEFs, differentiation
      proceeded in an insulin-independent manner. In conclusion, we suggest that pRB
      plays a pivotal role in adipogenesis by suppressing MAPK activity.

PMID- 12000770
TI  - The Escherichia coli gene encoding the UDP-2,3-diacylglucosamine pyrophosphatase
      of lipid A biosynthesis.
AB  - UDP-2,3-diacylglucosamine hydrolase is believed to catalyze the fourth step of
      lipid A biosynthesis in Escherichia coli. This reaction involves pyrophosphate
      bond hydrolysis of the precursor UDP-2,3-diacylglucosamine to yield 2,3
      diacylglucosamine 1-phosphate and UMP. To identify the gene encoding this
      hydrolase, E. coli lysates generated with individual lambda clones of the ordered
      Kohara library were assayed for overexpression of the enzyme. The sequence of
      lambda clone 157[6E7], promoting overproduction of hydrolase activity, was
      examined for genes encoding hypothetical proteins of unknown function. The amino
      acid sequence of one such open reading frame, ybbF, is 50.5% identical to a
      Haemophilus influenzae hypothetical protein and is also conserved in most other
      Gram-negative organisms, but is absent in Gram-positives. Cell extracts prepared
      from cells overexpressing ybbF behind the T7lac promoter have approximately 540
      times more hydrolase activity than cells with vector alone. YbbF was purified to
      approximately 60% homogeneity, and its catalytic properties were examined.
      Enzymatic activity is maximal at pH 8 and is inhibited by 0.01% (or more) Triton
      X-100. The apparent K(m) for UDP-2,3-diacylglucosamine is 62 microm. YbbF
      requires a diacylated substrate and does not cleave CDP-diacylglycerol. (31)P NMR
      studies of the UMP product generated from UDP-2,3-diacylglucosamine in the
      presence of 40% H(2)180 show that the enzyme attacks the alpha-phosphate group of
      the UDP moiety. Because ybbF encodes the specific UDP-2,3-diacylglucosamine
      hydrolase involved in lipid A biosynthesis, it is now designated lpxH.

PMID- 12000771
TI  - Accumulation of the lipid A precursor UDP-2,3-diacylglucosamine in an Escherichia
      coli mutant lacking the lpxH gene.
AB  - The lpxH gene encodes the UDP-2,3-diacylglucosamine-specific pyrophosphatase that
      catalyzes the fourth step of lipid A biosynthesis in Escherichia coli. To confirm
      the function of lpxH, we constructed KB21/pKJB5. This strain contains a kanamycin
      insertion element in the chromosomal copy of lpxH, complemented by plasmid pKJB5,
      which is temperature-sensitive for replication and harbors lpxH(+). KB21/pKJB5
      grows at 30 degrees C but loses viability at 44 degrees C, demonstrating that
      lpxH is essential. CDP-diglyceride hydrolase (Cdh) catalyzes the same reaction as
      LpxH in vitro but is non-essential and cannot compensate for the absence of LpxH.
      The presence of Cdh in cell extracts interferes with the LpxH assay. We therefore
      constructed KB25/pKJB5, which contains both an in-frame deletion of cdh and a
      kanamycin insertion mutation in lpxH, covered by pKJB5. When KB25/pKJB5 cells are
      grown at 44 degrees C, viability is lost, and all in vitro LpxH activity is
      eliminated. A lipid migrating with synthetic UDP-2,3-diacylglucosamine
      accumulates in KB25/pKJB5 following loss of the covering plasmid at 44 degrees C.
      This material was converted to the expected products, 2,3-diacylglucosamine 1
      phosphate and UMP, by LpxH. Pseudomonas aeruginosa contains two proteins with
      sequence similarity to E. coli LpxH. The more homologous protein catalyzes UDP
      2,3-diacylglucosamine hydrolysis in vitro. The corresponding gene complements
      KB25/pKJB5 at 44 degrees C, but the less homologous gene does not. The
      accumulation of UDP-2,3-diacylglucosamine in our lpxH mutant is consistent with
      the observation that the lipid A disaccharide synthase LpxB, the next enzyme in
      the pathway, cannot condense two UDP-2,3-diacylglucosamine molecules, but instead
      utilizes UDP-2,3-diacylglucosamine as its donor and 2,3-diacylglucosamine 1
      phosphate as its acceptor.

PMID- 12000772
TI  - Franchising of health services in low-income countries.
AB  - Grouping existing providers under a franchised brand, supported by training,
      advertising and supplies, is a potentially important way of improving access to
      and assuring quality of some types of clinical medical services. While
      franchising has great potential to increase service delivery points and method
      acceptability, a number of challenges are inherent to the delivery model:
      controlling the quality of services provided by independent practitioners is
      difficult, positioning branded services to compete on either price or quality
      requires trade-offs between social goals and provider satisfaction, and
      understanding the motivations of clients may lead to organizational choices which
      do not maximize quality or minimize costs. This paper describes the structure and
      operation of existing franchises and presents a model of social franchise
      activities that will afford a context for analyzing choices in the design and
      implementation of health-related social franchises in developing countries.

PMID- 12000773
TI  - Making medicine for the poor: primary health care interpretations in Pelotas,
      Brazil.
AB  - This paper explores the local political setting in which primary health care and
      community participation have been implemented in Pelotas, Brazil over the past
      two decades. We argue that in a medically plural setting with a mixture of
      private and public health care schemes, capitalist-based principles and ideals
      (such as the predominant role given to technology) shape generalized concepts of
      good clinical skills and quality of care, thereby regulating the medical system
      as a whole. The analysis shows that some women living in shantytowns reject the
      negative class-based associations made with their communities in a variety of
      ways, including the non-use of their local primary health care (PHC) centre which
      they considered to be a poor substitute for what the wealthy take for granted.
      Recent studies show that primary level antenatal care is of low quality when
      compared with other sectors. Nevertheless, local politicians and physicians often
      blamed various aspects of local 'culture' (folk health beliefs, low valuing of
      biomedicine, lack of modern concepts of community-building and altruism) for
      failed PHC programmes, contributing a prejudicial feedback cycle between
      frustrated professionals often engaging in prejudicial clinical practices and
      offended users. Rather than discuss community participation through vague
      concepts such as empowerment and citizenship, those involved in PHC reform would
      do well to take explicit (publicly stated) responsibility for the socio
      political, financial and bureaucratic constraints to PHC.

PMID- 12000774
TI  - A comparative cost analysis of insecticide-treated nets and indoor residual
      spraying in highland Kenya.
AB  - The relative cost of indoor residual house-spraying (IRS) versus insecticide
      treated bednets (ITNs) forms part of decisions regarding selective malaria
      prevention. This paper presents a cost comparison of these two approaches as
      recently implemented by Merlin, a UK emergency relief organization funded through
      international donor support and working in the highland districts of Gucha and
      Kisii in Kenya. The financial costs (cash expenditures) and the economic costs
      (including the opportunity costs of using existing staff and volunteers, and an
      annualized cost for capital items) were assessed. The financial cost for IRS was
      US dollars 0.86 per person protected, compared with 4.21 dollars for ITNs
      (reducing to 3.42 dollars to the provider assuming cost recovery). The economic
      cost per person protected for IRS was 0.88 dollars, compared with 2.34 dollars
      for ITNs. The costs for ITNs were sensitive to the number of nets sold per
      community group ('efficiency'), as the delivery costs constituted upwards of 40%
      of the total cost. However, even marked increases in efficiency of these groups
      could not reduce the costs of ITNs to that comparable with IRS, except if more
      than one cycle of IRS was needed. The implications of predicted reductions in the
      cost of insecticide for both IRS and ITNs are also explored. The provision of
      itemized cost data allows predictions to be made on changes in the design of
      these programmes. Under almost all design scenarios, IRS would appear to be a
      more cost-efficient means of vector control in the Kenyan highlands.

PMID- 12000775
TI  - Free formula milk for infants of HIV-infected women: blessing or curse?
AB  - There is vigorous controversy around whether HIV-infected women in developing
      countries should choose formula or breastfeeding for their infants. Formula
      eliminates HIV transmission but incurs risk of increased mortality, whereas
      breastfeeding has multiple benefits but entails risk of HIV transmission.
      International guidelines are available but need to be strengthened. This
      commentary summarizes data on the scale and rate of mother-to-child transmission
      (MTCT) of HIV through breastfeeding, and the hazards and benefits of breast- and
      formula-feeding. The case against providing free or subsidized formula to HIV
      infected mothers is based on the following: it exacerbates disadvantages of
      formula feeding; compromises free choice; targets beneficiaries erroneously;
      creates a false perception of endorsement by health workers; compromises
      breastfeeding; results in disclosure of HIV status; ignores hidden costs of
      preparation of formula; increases mixed breastfeeding, which is an unsatisfactory
      method for all women; requires organization and management of programmes that are
      complicated and costly; and finally increases the 'spill-over' effect into the
      normal breastfeeding population. Recommendations to minimize these drawbacks
      include use of affordable antiretrovirals to reduce MTCT; investments in high
      quality, widely available HIV counselling; support for choice of feeding; and
      exclusive breastfeeding for those who choose to breastfeed.

PMID- 12000776
TI  - 'Lifelong investment in health': the discursive construction of 'problems' in
      Hong Kong health policy.
AB  - This paper reflects on the contemporary health policy debate in Hong Kong, and
      the shape assigned to particular 'problems'. Health reform discourses are
      identified to reveal the tensions that exist between the dominant biomedical
      discourse that focuses on individual responsibility, lifestyle change and health
      education while articulating a community development approach to health care
      reform. A critical review of the Consultation Document on Health Care Reform in
      Hong Kong, entitled Lifelong Investment in Health, will reveal a rhetorical
      commitment to health care reform alongside proposals that suggest little
      understanding of the changes required to implement such reform. In fact, the
      document proposes a model of health care that not only remains within the
      biomedical paradigm, but which if enacted may extend the influence of medicine
      into the psychosocial sphere. Edelman has defined policy as 'a set of shifting,
      diverse, and contradictory responses to a spectrum of political interests'. The
      starting point from this perspective is the identification of the discursive
      construction of policy problems and the associated 'spectrum of political
      interests'. It is an attempt to reveal the operation of power in places in which
      administrative, political and professional discourses tend to obscure it.

PMID- 12000777
TI  - Access as a factor in differential contraceptive use between Mayans and ladinos
      in Guatemala.
AB  - Previous studies have demonstrated consistently that the Mayan women of Guatemala
      have a far lower level of contraceptive use than their ladino counterparts (e.g.
      50% versus 13% in the 1998 Demographic and Health Survey - DHS). Most researchers
      and practitioners have attributed this to social, economic and cultural
      differences between the two groups that result in Mayans having a far lower
      demand for family planning than ladinos. This paper tests an alternative
      hypothesis: that the contraceptive supply environment may be more limited for
      Mayans than ladinos. This analysis uses an innovative approach of linking
      household level data from the 1995/6 Guatemala DHS and with facility-level data
      from the 1997 Providers Census for four highland departments in which the latter
      was conducted. On average, married women of reproductive age in the four
      departments lived 2 km from a facility that provided some type of contraception.
      Mayans and ladinos did not differ significantly in terms of (1) mean distance to
      the closest facility offering family planning services, or (2) mean distance to a
      facility providing each specific method (except injectables). Mayans were more
      likely to live closer to an APROFAM clinic, whereas ladinos were closer to a
      facility that offered access to injectables. Otherwise, the family planning
      supply environment differed little for the two groups. However, access may not be
      the determining factor in contraceptive use, given that less than 8% of users got
      their (last) contraceptive from the nearest facility. Moreover, APROFAM - which
      was the nearest facility for only 7% of the respondents in this study - was the
      source of supply for 48% of users. Although this study does not directly measure
      quality, the characteristics that differentiate APROFAM from other service
      providers point to quality as more important than physical access or cost in
      source of contraception among this group of users.

PMID- 12000778
TI  - Costs and cost-effectiveness of different DOT strategies for the treatment of
      tuberculosis in Pakistan. Directly Observed Treatment.
AB  - An economic study was conducted alongside a clinical trial at three sites in
      Pakistan to establish the costs and effectiveness of different strategies for
      implementing directly observed treatment (DOT) for tuberculosis. Patients were
      randomly allocated to one of three arms: DOTS with direct observation by health
      workers (at health centres or by community health workers); DOTS with direct
      observation by family members; and DOTS without direct observation. The clinical
      trial found no statistically significant difference in cure rate for the
      different arms. The economic study collected data on the full range of health
      service costs and patient costs of the different treatment arms. Data were also
      disaggregated by gender, rural and urban patients, by treatment site and by
      economic categories, to investigate the costs of the different strategies, their
      cost-effectiveness and the impact that they might have on patient compliance with
      treatment. The study found that direct observation by health centre-based health
      workers was the least cost-effective of the strategies tested (US dollars 310 per
      case cured). This is an interesting result, as this is the model recommended by
      the World Health Organization and International Union against Tuberculosis and
      Lung Disease. Attending health centres daily during the first 2 months generated
      high patient costs (direct and in terms of time lost), yet cure rates for this
      group fell below those of the non-observed group (58%, compared with 62%). One
      factor suggested by this study is that the high costs of attending may be
      deterring patients, and in particular, economically active patients who have most
      to lose from the time taken by direct observation. Without stronger evidence of
      benefits, it is hard to justify the costs to health services and patients that
      this type of direct observation imposes. The self-administered group came out as
      most cost-effective (164 dollars per case cured). The community health worker sub
      group achieved the highest cure rates (67%), with a cost per case only slightly
      higher than the self-administered group (172 dollars per case cured). This
      approach should be investigated further, along with other approaches to improving
      patient compliance.

PMID- 12000779
TI  - Assessing the cost and willingness to pay for voluntary HIV counselling and
      testing in Kenya.
AB  - OBJECTIVE: Voluntary counselling and testing (VCT) should be an important
      component in a country's HIV/AIDS prevention and care strategy. However, the high
      cost of VCT raises concerns about the affordability of VCT in low-income
      countries. This study was designed to assess the costs of VCT and to identify
      potential ways of introducing VCT more affordably. METHODOLOGY: An economic
      evaluation was performed of VCT services in two rural health centres in Thika
      District and an urban health centre in Nairobi, Kenya. A contingent valuation
      study was also performed among VCT clients. Estimates were developed regarding
      the national cost of offering VCT services in Kenya. RESULTS: VCT added US
      dollars 6800 per year to the average cost of providing services at each of these
      three health centres. The evaluation revealed that the incremental cost, from the
      government's perspective, of adding VCT is approximately 16 dollars per client.
      The estimated incremental cost per client is significantly less than a previous
      cost estimate in Kenya which estimated a cost per client of 26 dollars. The
      difference in cost estimates is in part attributable to the emphasis of this
      project on integrating VCT services into existing health centres, rather than
      creating stand-alone sites. The cost of VCT services might be further reduced to
      as little as 8 dollars per client if a government health worker could perform the
      counselling. A contingent valuation study indicated that most VCT clients would
      be willing to pay at least 2 dollars for the service. However, if the full cost
      of the service were charged to the client, less than 5% of clients indicated they
      were willing and able to pay for the service. CONCLUSIONS: Integrating services
      into existing health centres can significantly reduce the cost of VCT. Additional
      cost reductions may be feasible if health centre staff are hired to perform the
      counselling. Furthermore, it appears that some level of cost recovery from VCT
      clients is feasible and can contribute to sustainability, although it is very
      unlikely that the full cost of the service could be recovered from the clients.
      The national provision of VCT in all Kenyan health centres is likely to be an
      affordable option, although additional operational research is required to
      determine the most appropriate way of scaling up VCT services throughout the
      country.

PMID- 12000780
TI  - Translating HIV/AIDS research findings into policy: lessons from a case study of
      'the Mwanza trial'.
AB  - The scale and severity of the impact of the global HIV/AIDS pandemic on low
      income countries, mainly those in sub-Saharan Africa, is almost unimaginable to
      people in high-income countries. There is a particularly pressing need to
      understand better how to ensure the translation into policy and practice of
      important research findings in HIV/AIDS prevention and care in countries
      threatened by fast spreading HIV epidemics. The purpose of this paper is to
      review the findings and implications of a policy analysis case study of an
      HIV/AIDS clinical trial that has been successful in influencing HIV prevention
      policy relevant to low-income countries, in order to identify illustrative
      lessons for HIV/AIDS researchers in the future. The case study sought to detail
      the interaction between researchers and policy-makers for this particular case
      study to ascertain detailed analysis by these two groups on the interaction
      between research and policy. The major findings of the policy analysis case study
      were that policy shift was a cumulative but non-linear process, with the Mwanza
      trial placing a crucial role in both boosting and confirming existing policy
      movements. Researchers and policy-makers held similar longitudinal views of the
      process and political environment. Key moments of communication tended to involve
      personal contact. The important role played by people and organizations who could
      work in both the research and policy communities was often mentioned as crucial
      in enabling research relevant policy shifts. Researchers may absorb themselves in
      the technicalities of their study without considering their role in pursuing the
      wider policy implications. The impact of research on policy must be an integral
      element of every stage of the research process. The case study illustrates the
      need to take a contextual view of the interaction between research and policy,
      and understand how changing political contexts affect receptivity to research
      outcomes. This will increase the likelihood of research findings having an impact
      on policy. The review reflects the authors' experiences of working for
      organizations in non-governmental organization, bilateral development agency and
      academic settings.

PMID- 12000781
TI  - Local governance and community financing of primary care: evidence from Nepal.
AB  - Improved community participation in the financing of primary health care (PHC) is
      important for sustaining quality and availability of care in developing
      countries. This study asks whether the social status of members on a local
      support committee is associated with community contributions to PHC. A survey of
      PHC financing was conducted at 42 health facilities in two rural districts of
      Nepal (Jumla and Nawal Parasi). Complete data were available for 37 clinics. At
      each health facility, a trained interviewer collected information from the clinic
      administrator about the caste characteristics of the Village Development
      Committees (VDC) and the financial contributions made by VDCs towards the
      operation of the health facilities. Bivariate and multivariate logistic
      regression assessed the likelihood of financial contribution as it related to the
      caste and gender composition of the VDC as well as other characteristics of the
      VDC and the facility. VDCs with a majority of committee members in castes other
      than the highest two had higher odds of contributing to the health centre. We
      conclude that local development committees with a greater representation of
      middle and low caste members are more likely to contribute financially to the
      local health facility. Future research must determine the factors that lead some
      villages to include low caste villagers in local government.

PMID- 12000782
TI  - Managing a household survey: a practical example from the KENQOL survey. Kenya
      Quality of Life.
AB  - It is vital that surveys are well managed for results to be reliable and
      meaningful. Poorly managed surveys can result in falsified, lost or incomplete
      data. Good management requires time to plan and think about all those involved in
      the process of the survey: the respondents, interviewers, supervisors, coders and
      the wider community. This paper draws on our experience of running a randomized
      household survey in three locations in the rural area of Makueni district,
      Eastern Kenya. The paper outlines the various strategies used to: gain access to
      the local community; recruit and train interviewers; supervise; plan day to day
      activities; and manage data.

PMID- 12000783
TI  - The Asian Voice in building equity in health for development - from the Asian
      Forum for Health Research, Manila, February 2000.
AB  - The Asian Forum for Health Research convened in Manila, the Philippines, in
      February 2000 to determine how best to create a new paradigm for health research
      in Asia. The forum was organized as an 'open university of research for equity in
      health development' to define the new paradigm and to identify methods for
      building a dynamic and collaborative architecture to more effectively link the
      nations and region of Asia with global stakeholders in health research. It was
      also to: determine Asian actions required to enhance leadership functions for
      innovative health research management; develop and disseminate tools and
      methodologies needed to accomplish essential tasks; establish collaborative
      networks within developing countries/regions to ensure efforts are not duplicated
      and international inputs are not monopolized; and use new information and
      communication technologies to integrate the process and contents of health
      research with equity in health development. Results of the forum's review of
      issues were presented and discussed at the International Conference on Health
      Research for Development, held in October 2000 in Bangkok, Thailand.

PMID- 12000784
TI  - Clarifying the case on the role and limitations of private health care in
      Nigeria.

PMID- 12000786
TI  - Why do miRNAs live in the miRNP?

PMID- 12000787
TI  - Role of Rho family GTPases in epithelial morphogenesis.

PMID- 12000788
TI  - Wingful, an extracellular feedback inhibitor of Wingless.
AB  - Secreted peptide signals control many fundamental processes during animal
      development. Proper responses to these signals require cognate inducible feedback
      antagonists. Here we report the identification of a novel Drosophila Wingless
      (Wg) target gene, wingful (wf), and show that it encodes a potent extracellular
      feedback inhibitor of Wg. In contrast to the cytoplasmic protein Naked cuticle
      (Nkd), the only known Wg feedback antagonist, Wf functions during larval stages,
      when Nkd function is dispensable. We propose that Wf may provide feedback control
      for the long-range morphogen activities of Wg.

PMID- 12000789
TI  - Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma
      development in the mouse.
AB  - Biallelic NF2 gene inactivation is common in sporadic and in neurofibromatosis
      type 2 (NF2)-related meningiomas. We show that, beginning at four months of age,
      thirty percent of mice with arachnoidal cell Cre-mediated excision of Nf2 exon 2
      developed a range of meningioma subtypes histologically similar to the human
      tumors. Additional hemizygosity for p53 did not modify meningioma frequency or
      progression suggesting that Nf2 and p53 mutations do not synergize in meningeal
      tumorigenesis. This first mouse model initiated with a genetic lesion found in
      human meningiomas provides a powerful tool for investigating tumor progression
      and for the preclinical evaluation of therapeutic interventions.

PMID- 12000790
TI  - Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch
      for the Wnt pathway.
AB  - The Wnt pathway controls numerous developmental processes via the beta-catenin
      TCF/LEF transcription complex. Deregulation of the pathway results in the
      aberrant accumulation of beta-catenin in the nucleus, often leading to cancer.
      Normally, cytoplasmic beta-catenin associates with APC and axin and is
      continuously phosphorylated by GSK-3beta, marking it for proteasomal degradation.
      Wnt signaling is considered to prevent GSK-3beta from phosphorylating beta
      catenin, thus causing its stabilization. However, the Wnt mechanism of action has
      not been resolved. Here we study the regulation of beta-catenin phosphorylation
      and degradation by the Wnt pathway. Using mass spectrometry and phosphopeptide
      specific antibodies, we show that a complex of axin and casein kinase I (CKI)
      induces beta-catenin phosphorylation at a single site: serine 45 (S45).
      Immunopurified axin and recombinant CKI phosphorylate beta-catenin in vitro at
      S45; CKI inhibition suppresses this phosphorylation in vivo. CKI phosphorylation
      creates a priming site for GSK-3beta and is both necessary and sufficient to
      initiate the beta-catenin phosphorylation-degradation cascade. Wnt3A signaling
      and Dvl overexpression suppress S45 phosphorylation, thereby precluding the
      initiation of the cascade. Thus, a single, CKI-dependent phosphorylation event
      serves as a molecular switch for the Wnt pathway.

PMID- 12000791
TI  - Y4 receptor knockout rescues fertility in ob/ob mice.
AB  - Hypothalamic neuropeptide Y (NPY) has been implicated in the regulation of energy
      balance and reproduction, and chronically elevated NPY levels in the hypothalamus
      are associated with obesity and reduced reproductive function. However, it is not
      known which one of the five cloned Y receptors mediates these effects. Here we
      show that crossing the Y4 receptor knockout mouse (Y4(-/-)) onto the ob/ob
      background restores the reduced plasma testosterone levels of ob/ob mice as well
      as the reduced testis and seminal vesicle size and morphology to control values.
      Fertility in the sterile ob/ob mice was greatly improved by Y4 receptor deletion,
      with 100% of male and 50% of female Y4(-/-),ob/ob double knockout mice producing
      live offspring. Development of the mammary ducts and lobuloalveoli was
      significantly enhanced in pregnant Y4(-/-) and Y4(-/-),ob/ob females. Consistent
      with the improved fertility and enhanced mammary gland development, gonadotropin
      releasing hormone (GnRH) expression was significantly increased in Y4(-/-) and
      Y4(-/-),ob/ob animals. Y4(-/-) mice displayed lower body weight and reduced white
      adipose tissue mass accompanied by increased plasma levels of pancreatic
      polypeptide (PP). However, Y4 deficiency had no beneficial effects to reduce body
      weight or excessive adiposity of ob/ob mice. These data suggest that central Y4
      receptor signaling specifically inhibits reproductive function under conditions
      of elevated central NPY-ergic tonus.

PMID- 12000792
TI  - The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and
      appendicular skeletal development.
AB  - Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll)
      gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in
      appendage development in essentially all species in which it has been identified.
      In Drosophila, Dll is expressed in the distal portion of the developing
      appendages and is critical for the development of distal structures. In addition,
      human Dlx5 and Dlx6 homeobox genes have been identified as possible candidate
      genes for the autosomal dominant form of the split-hand/split-foot malformation
      (SHFM), a heterogeneous limb disorder characterized by missing central digits and
      claw-like distal extremities. Targeted inactivation of Dlx5 and Dlx6 genes in
      mice results in severe craniofacial, axial, and appendicular skeletal
      abnormalities, leading to perinatal lethality. For the first time, Dlx/Dll gene
      products are shown to be critical regulators of mammalian limb development, as
      combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal
      specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of
      Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth.

PMID- 12000793
TI  - Initiation of tRNA maturation by RNase E is essential for cell viability in E.
      coli.
AB  - RNase E, an essential endoribonuclease in Escherichia coli, is involved in 9S
      rRNA processing, the degradation of many mRNAs, and the processing of the M1 RNA
      subunit of RNase P. However, the reason that RNase E is required for cell
      viability is still not fully understood. In fact, recent experiments have
      suggested that defects in 9S rRNA processing and mRNA decay are not responsible
      for the lack of cell growth in RNase E mutants. By using several new rne alleles,
      we have confirmed these observations and have also ruled out that M1 processing
      by RNase E is required for cell viability. Rather, our data suggest that the
      critical in vivo role of RNase E is the initiation of tRNA maturation.
      Specifically, RNase E catalytic activity starts the processing of both
      polycistronic operons, such as glyW cysT leuZ, argX hisR leuT proM, and lysT valT
      lysW valZ lysY lysZ lysQ, as well as monocistronic transcripts like pheU, pheV,
      asnT, asnU, asnV, and asnW. Cleavage by RNase E within a few nucleotides of the
      mature 3' CCA terminus is required before RNase P and the various 3' --> 5'
      exonucleases can complete tRNA maturation. All 59 tRNAs tested involved RNase E
      processing, although some were cleaved more efficiently than others.

PMID- 12000794
TI  - An mt(+) gamete-specific nuclease that targets mt(-) chloroplasts during sexual
      reproduction in C. reinhardtii.
AB  - Although the active digestion of mating-type minus (mt-) chloroplast DNA (cpDNA)
      in young zygotes is considered to be the basis for the uniparental inheritance of
      cpDNA in Chlamydomonas reinhardtii, little is known about the underlying
      molecular mechanism. One model of active digestion proposes that nucleases are
      either synthesized or activated to digest mt- cpDNA. We used a native-PAGE/in
      gelo assay to investigate nuclease activities in chloroplasts from young zygotes,
      and identified a novel Ca(2+)-dependent nuclease activity. The timing of
      activation (approximately 60-90 min after mating) and the localization of the
      nuclease activity (in mt- chloroplasts) coincided with the active digestion of mt
      cpDNA. Furthermore, the activity of the nuclease was coregulated with the
      maturation of mating-type plus (mt+) gametes, which would enable the efficient
      digestion of mt- cpDNA. Based on these observations, we propose that the nuclease
      (designated as Mt(+)-specific DNase, MDN) is a developmentally controlled
      nuclease that is activated in mt+ gametes and participates in the destruction of
      mt- cpDNA in young zygotes, thereby ensuring uniparental inheritance of
      chloroplast traits.

PMID- 12000795
TI  - WUSCHEL signaling functions in interregional communication during Arabidopsis
      ovule development.
AB  - Coordinating the behaviors of different cell populations is essential for
      multicellular development. One important example for this can be found in ovule
      development in higher plants. Ovules give rise to the gametophyte in the distal
      nucellus and form protective sporophytic organs from the underlying chalaza. We
      show that the WUSCHEL (WUS) homeobox gene provides a mechanism to coordinate
      these events. WUS is expressed in the nucellus and our loss- and gain-of-function
      analyses show that WUS is not only necessary but also sufficient for integument
      formation from the chalaza. WUS protein is retained in the nucellus, indicating
      that WUS activity in the nucellus generates a downstream signal that non-cell
      autonomously regulates integument initiation in the chalaza. This signal appears
      to act locally, thus determining the position of organ formation from chalazal
      cells adjacent to the nucellus. Analysis of WUS and AINTEGUMENTA functions
      indicates that integument initiation requires inputs from different ovule
      regions. Together with previous findings for shoot and floral meristems, where
      WUS signaling establishes a stem cell niche, our results indicate that WUS
      defines a signaling mechanism that is used repeatedly during plant development in
      coordinating the behavior of adjacent cell groups.

PMID- 12000796
TI  - Targets of AtWRKY6 regulation during plant senescence and pathogen defense.
AB  - In Arabidopsis, WRKY factors comprise a large gene family of plant-specific
      transcriptional regulators controlling several types of plant stress responses.
      To understand the regulatory role of WRKY proteins during such processes, we
      identified targets of the senescence- and defense-associated WRKY6 factor. WRKY6
      was found to suppress its own promoter activity as well as that of a closely
      related WRKY family member, indicating negative autoregulation. On the other
      hand, WRKY6 positively influenced the senescence- and pathogen defense-associated
      PR1 promoter activity, most likely involving NPR1 function. One novel identified
      target gene, SIRK, encodes a receptor-like protein kinase, whose developmental
      expression is strongly induced specifically during leaf senescence. The
      transcriptional activation of SIRK is dependent on WRKY6 function. Senescing
      leaves of wrky6 knockout mutants showed a drastic reduction, and green leaves of
      WRKY6 overexpression lines showed clearly elevated SIRK transcript levels.
      Furthermore, the SIRK gene promoter was specifically activated by WRKY6 in vivo,
      functioning very likely through direct W-box interactions.

PMID- 12000797
TI  - Hox gene control of segment-specific bristle patterns in Drosophila.
AB  - Hox genes specify the different morphologies of segments along the
      anteroposterior axis of animals. How they control complex segment morphologies is
      not well understood. We have studied how the Hox gene Ultrabithorax (Ubx)
      controls specific differences between the bristle patterns of the second and
      third thoracic segments (T2 and T3) of Drosophila melanogaster. We find that Ubx
      blocks the development of two particular bristles on T3 at different points in
      sensory organ development. For the apical bristle, a precursor is singled out and
      undergoes a first division in both the second and third legs, but in the third
      leg further differentiation of the second-order precursors is blocked. For the
      posterior sternopleural bristle, development on T3 ceases after proneural cluster
      initiation. Analysis of the temporal requirement for Ubx shows that in both cases
      Ubx function is required shortly before bristle development is blocked. We
      suggest that interactions between Ubx and the bristle patterning hierarchy have
      evolved independently on many occasions, affecting different molecular steps. The
      effects of Ubx on bristle development are highly dependent on the context of
      other patterning information. Suppression of bristle development or changes in
      bristle morphology in response to endogenous and ectopic Ubx expression are
      limited to bristles at specific locations.

PMID- 12000798
TI  - Jumping and kicking in the false stick insect Prosarthria teretrirostris:
      kinematics and motor control.
AB  - The false stick insect Prosarthria teretrirostris looks and behaves like a real
      stick insect but can jump and kick rapidly and powerfully like a locust, to which
      it is more closely related. It has an elongated body with slender hind legs that
      are some 2.5 times longer than the front and middle legs. A male with a body 67
      mm long and weighing 0.28 g can jump 90 cm with a take-off angle of 40 degrees
      and velocity of 2.5 ms(-1), requiring an energy expenditure of 850 microJ. The
      body is accelerated at 165 ms(-2) for only 30 ms. The larger and heavier females
      (mean body length 104 mm and weighing 1.5 g) can jump on average a distance of 49
      cm. During jumping, the tibiae of the hind legs are extended in 30 ms with
      maximum rotational velocities of 11.5 degrees per ms, but during kicking, when
      there is no body weight to support, extension is complete in 7 ms with rotational
      velocities as high as 48 degrees per ms. The short time available to accelerate
      the body indicates that the movements are not powered by direct muscle
      contractions and that there must be storage of elastic energy in advance. The
      motor patterns responsible for generating the necessary forces in the hind legs
      for jumping and kicking are similar and consist of three phases; an initial
      flexion of the tibia is followed by a co-contraction of the small flexor and
      large extensor tibiae muscles lasting several hundred milliseconds while the
      tibia remains fully flexed. Finally, the flexor motor neurons stop spiking so
      that the tibia is able to extend rapidly. The small semi-lunar processes at the
      femoro-tibial joints are not distorted, so that they cannot act as energy stores.
      Some 7% of the energy is stored transiently by bending the thin tibiae during the
      initial acceleration phase of a jump and releasing it just before take-off. The
      jumping and kicking mechanisms of Prosarthria teretrirostris have features in
      common with those used by locusts but also have their own characteristics. The
      evolution of jumping in Orthoptera is discussed in this context.

PMID- 12000799
TI  - The locust tegula: kinematic parameters and activity pattern during the wing
      stroke.
AB  - The tegula is a complex, knob-shaped sense organ associated with the base of the
      locust wing. Despite a detailed knowledge of its role in flight motor control,
      little is known about the relationship between the stroke parameters of the wing,
      movement of the tegula organ and the pattern of tegula activity. In this study,
      therefore, the kinematic parameters of the fore- and hindwings were investigated
      with respect to the tegula activity pattern during tethered flight. The following
      results were obtained. (i) The tegula moves through a complex three-dimensional
      trajectory during the wing stroke, involving inclination and rotation about its
      longitudinal axis. (ii) The kinematic parameters of tegula movement are phase
      locked to the wing stroke and vary in conjunction with wing stroke parameters
      such as amplitude and cycle period. (iii) In accordance with these phase-locked
      kinematics, both the onset of tegula activity with respect to the downstroke
      (latency) and the discharge of the organ (burst duration and amplitude) vary in
      conjunction with downstroke movement and cycle period, resulting in an (almost)
      constant phase of tegula activation during the stroke cycle. (iv) The pattern of
      tegula activity during flight is largely independent of stroke amplitude. (v) The
      latency, burst duration and amplitude of tegula activity are strongly related to
      the angular velocity of the wing during the downstroke, with latency reaching a
      steady minimum value at higher angular velocities. The data suggest that the
      tegula encodes the timing and velocity of the downstroke and that it may be
      involved in the control of the stroke's angular velocity.

PMID- 12000800
TI  - The aerodynamics of revolving wings I. Model hawkmoth wings.
AB  - Recent work on flapping hawkmoth models has demonstrated the importance of a
      spiral 'leading-edge vortex' created by dynamic stall, and maintained by some
      aspect of spanwise flow, for creating the lift required during flight. This study
      uses propeller models to investigate further the forces acting on model hawkmoth
      wings in 'propeller-like' rotation ('revolution'). Steadily revolving model
      hawkmoth wings produce high vertical ( approximately lift) and horizontal (
      approximately profile drag) force coefficients because of the presence of a
      leading-edge vortex. Both horizontal and vertical forces, at relevant angles of
      attack, are dominated by the pressure difference between the upper and lower
      surfaces; separation at the leading edge prevents 'leading-edge suction'. This
      allows a simple geometric relationship between vertical and horizontal forces and
      the geometric angle of attack to be derived for thin, flat wings. Force
      coefficients are remarkably unaffected by considerable variations in leading-edge
      detail, twist and camber. Traditional accounts of the adaptive functions of twist
      and camber are based on conventional attached-flow aerodynamics and are not
      supported. Attempts to derive conventional profile drag and lift coefficients
      from 'steady' propeller coefficients are relatively successful for angles of
      incidence up to 50 degrees and, hence, for the angles normally applicable to
      insect flight.

PMID- 12000801
TI  - The aerodynamics of revolving wings II. Propeller force coefficients from mayfly
      to quail.
AB  - High force coefficients, similar to those observed for revolving model hawkmoth
      wings in the accompanying paper (for which steady leading-edge vortices are
      directly observed), are apparent for revolving model (mayfly, bumblebee and
      quail) and real (quail) animal wings ranging in Reynolds number (Re) from 1100 to
      26000. Results for bumblebee and hawkmoth wings agree with those published
      previously for Drosophila (Re approximately 200). The effect of aspect ratio is
      also tested with planforms based on hawkmoth wings adjusted to aspect ratios
      ranging from 4.53 to 15.84 and is shown to be relatively minor, especially at
      angles of incidence below 50 degrees. The normal force relationship introduced in
      the accompanying paper is supported for wings over a large range of aspect ratios
      in both 'early' and 'steady' conditions; local induced velocities appear not to
      affect the relationship.

PMID- 12000802
TI  - The heart of Ciona intestinalis: eicosanoid-generating capacity and the effects
      of precursor fatty acids and eicosanoids on heart rate.
AB  - Eicosanoids are a group of oxygenated fatty-acid derivatives formed from C20
      polyunsaturated fatty acids including arachidonic and eicosapentaenoic acids. In
      mammals, these compounds have been shown to be key molecules in several
      physiological processes including regulation of the vascular system. This study
      determined whether eicosanoids or their precursors are involved in the regulation
      of heart rate in the sea squirt Ciona intestinalis. Eicosanoid generation by both
      heart and blood cells was measured. The major lipoxygenase products formed were
      both derivatives of eicosapentaenoic acid, namely 8- and 12
      hydroxyeicosapentaenoic acids (8-HEPE and 12-HEPE). Smaller amounts of 8,15
      dihydroxyeicosapentaenoic acid (8,15-diHEPE) were also formed. The cyclo
      oxygenase product prostaglandin E was also found in small amounts in the heart.
      Isolated hearts were exposed either to these fatty acid precursors or to 8-HEPE,
      12-HEPE or prostaglandin E3, and the effect on heart rate was recorded. Both
      eicosapentaenoic and arachidonic acids stimulated the heart rate at
      concentrations between 50 and 200 micromol l(-1). 12-HEPE (5 micromol l(-1)) and
      prostaglandin E3 (50 micromoll(-1)) caused a modest increase in heart rate, while
      8-HEPE had no significant effects at any of the time periods studied (<or=180
      min). Overall, the results show that arachidonic and eicosapentaenoic acids have
      limited effects on heart rate and only at concentrations unlikely to be routinely
      liberated in vivo. Similarly, the eicosanoids tested had a minor stimulatory
      activity on heart rate. The potential mechanisms for this stimulation are
      discussed. Overall, these results suggest that such compounds are of limited
      importance in regulating the heart and vascular system of sea squirts.

PMID- 12000803
TI  - Isometric and isovelocity contractile performance of red muscle fibres from the
      dogfish Scyliorhinus canicula.
AB  - Maximum isometric tetanic force produced by bundles of red muscle fibres from
      dogfish, Scyliorhinus canicula (L.), was 142.4+/-10.3 kN m(-2) (N=35 fibre
      bundles); this was significantly less than that produced by white fibres 289.2+/
      8.4 kN m(-2) (N=25 fibre bundles) (means +/- S.E.M.). Part, but not all, of the
      difference is due to mitochondrial content. The maximum unloaded shortening
      velocity, 1.693+/-0.108 L(0) s(-1) (N=6 fibre bundles), was measured by the slack
      test method. L(0) is the length giving maximum isometric force. The
      force/velocity relationship was investigated using a step-and-ramp protocol in
      seven red fibre bundles. The following equation was fitted to the data:
      [(P/P(0))+(a/P(0))](V+b)=[(P(0)(*)/P(0))+(a/P(0))]b, where P is force during
      shortening at velocity V, P(0) is the isometric force before shortening, and a, b
      and P(0)(*) are fitted constants. The fitted values were P(0)(*)/P(0)=1.228+/
      0.053, V(max)=1.814+/-0.071 L(0) s(-1), a/P(0)=0.269+/-0.024 and b=0.404+/-0.041
      L(0) s(-1) (N=7 for all values). The maximum power was 0.107+/-0.005P(0)V(max)
      and was produced during shortening at 0.297+/-0.012V(max). Compared with white
      fibres from dogfish, the red fibres have a lower P(0) (49%) and V(max) (48%), but
      the shapes of the force/velocity curves are similar. Thus, the white and red
      fibres have equal capacities to produce power within the limits set by the
      isometric force and maximum velocity of shortening of each fibre type. A step
      shortening of 0.050+/-0.003L(0) (N=7) reduced the maximum isometric force in the
      red fibres' series elasticity to zero. The series elasticity includes all elastic
      structures acting in series with the attached cross-bridges. Three red fibre
      bundles were stretched at a constant velocity, and force (measured when length
      reached L(0)) was 1.519+/-0.032P(0). In the range of velocities used here, -0.28
      to -0.63V(max), force varied little with the velocity.

PMID- 12000804
TI  - Regulation of cardiac contractility in a cold stenothermal fish, the burbot Lota
      lota L.
AB  - In the present study, burbot (Lota lota L.) was used as a model to study the
      effects of acute temperature changes on cardiac contractility in a cold
      stenothermal fish. The burbot were captured in the breeding season (February) and
      were maintained for 4 weeks at 1-2 degrees C in the laboratory before the
      contractile properties of the heart were measured. Both isometric force and the
      pumping capacity of in vitro perfused hearts were maximum at the acclimation
      temperature (1 degrees C) and declined markedly when the temperature increased.
      At 1 degrees C heart rate was 25 beats min(-1) and increased to a maximum of 72
      beats min(-1) at 18 degrees C, above which atrio-ventricular block was observed.
      Ryanodine (10 micromol l(-1)), an inhibitor of sarcoplasmic reticulum (SR) Ca2+
      release channels, reduced the maximum developed force of paced atrial and
      ventricular preparations at 1 degrees C by 32+/-8 % and 16+/-3 %, respectively.
      At 7 degrees C, ryanodine-induced inhibition of force increased to 52+/-3 % and
      44+/-5 % in the atrium and ventricle, respectively. At 1 degrees C, ryanodine
      abolished rest-potentiation and turned it into rest-decay in both atrial and
      ventricular muscle. Ryanodine, however, had no effect on the mechanical
      refractory period or on the rate constants of mechanical and relaxation
      restitution in either preparation at 1 degrees C. The activity of myofibrillar
      Ca2+Mg2+-ATPase was higher in atrial than ventricular muscle and the temperature
      optimum of the ATPase in vitro was approximately 10 degrees C in both
      preparations. Our results indicate a significant dependence on SR Ca2+ stores for
      contractile activation in the burbot heart at temperatures that are known to
      inhibit SR function in mammalian heart. This suggests that the ryanodine
      receptors of the teleost heart, unlike those of the endotherms, are not leaky as
      temperatures approach 0 degrees C. Reliance on SR Ca2+ stores in both cold
      stenothermal burbot and cold-acclimated eurythermal teleosts suggests that
      enhanced SR Ca2+-release is a common characteristic of cold-living fish and may
      improve cardiac contractility in the cold.

PMID- 12000805
TI  - Doppler-shift compensation behavior in horseshoe bats revisited: auditory
      feedback controls both a decrease and an increase in call frequency.
AB  - Among mammals, echolocation in bats illustrates the vital role of proper audio
      vocal feedback control particularly well. Bats adjust the temporal, spectral and
      intensity parameters of their echolocation calls depending on the characteristics
      of the returning echo signal. The mechanism of audio-vocal integration in both
      mammals and birds is, however, still largely unknown. Here, we present behavioral
      evidence suggesting a novel audio-vocal control mechanism in echolocating
      horseshoe bats (Rhinolophus ferrumequinum). These bats compensate for even subtle
      frequency shifts in the echo caused by flight-induced Doppler effects by
      adjusting the frequency of their echolocation calls. Under natural conditions,
      when approaching background targets, the bats usually encounter only positive
      Doppler shifts. Hence, we commonly believed that, during this Doppler-shift
      compensation behavior, horseshoe bats use auditory feedback to compensate only
      for these increases in echo frequency (=positive shifts) by actively lowering
      their call frequency below the resting frequency (the call frequency emitted when
      not flying and not experiencing Doppler shifts). Re-investigation of the Doppler
      shift compensation behavior, however, shows that decreasing echo frequencies
      (=negative shifts) are involved as well: auditory feedback from frequencies below
      the resting frequency, when presented at similar suprathreshold intensity levels
      as higher echo frequencies, cause the bat's call frequency to increase above the
      resting frequency. However, compensation for negative shifts is less complete
      than for positive shifts (22% versus 95%), probably because of biomechanical
      restrictions in the larynx of bats. Therefore, Doppler-shift compensation
      behavior involves a quite different neural substrate and audio-vocal control
      mechanism from those previously assumed. The behavioral results are no longer
      consistent with solely inhibitory feedback originating from frequencies above the
      resting frequency. Instead, we propose that auditory feedback follows an
      antagonistic push/pull principle, with inhibitory feedback lowering and
      excitatory feedback increasing call frequencies. While the behavioral
      significance of an active compensation for echo frequencies below RF remains
      unclear, these behavioral results are crucial for determining the neural
      implementation of audio-vocal feedback control in horseshoe bats and possibly in
      mammals in general.

PMID- 12000806
TI  - The digestive tract of Nautilus pompilius (Cephalopoda, Tetrabranchiata): an X
      ray analytical and computational tomography study on the living animal.
AB  - Using X-ray analytical studies and computational tomography, the position of the
      digestive tract of the tetrabranchiate cephalopod Nautilus pompilius L. was
      demonstrated in a living animal. For the first time, a detailed analysis of the
      rate of digestion and the duration of the different phases of a digestive cycle
      has been made using these in vivo methods. At 20 min after food intake, the food
      has entered the stomach, where it is reduced to small pieces; most is stored in
      the crop, which is enlarged to approximately four times its original size. The
      chyme reaches the midgut gland 3 h and the rectal loop 5 h after food intake. The
      time between food intake and elimination is 12 h. Thus, in Nautilus pompilius,
      digestion takes approximately the same time as described for nectobenthic
      sepioids and benthic octopods but is approximately 6 h longer than in loliginids,
      which have a pelagic mode of life. Furthermore, the three-dimensional structure
      of the digestive tract of a living Nautilus pompilius L. was demonstrated using
      computational tomography.

PMID- 12000807
TI  - Differential expression of mitochondria-encoded genes in a hibernating mammal.
AB  - A cDNA library constructed from kidney of the thirteen-lined squirrel,
      Spermophilus tridecemlineatus, was differentially screened for genes that were
      upregulated during hibernation. A clone encoding cytochrome c oxidase subunit 1
      was found and confirmed to have been upregulated by northern blotting.
      Differential expression of Cox1 mRNA occurred in multiple organs during
      hibernation; in hibernating animals transcript levels were twofold higher in
      kidney and fourfold higher in heart and brown adipose tissue than in euthermic
      animals, but were unchanged in skeletal muscle. Transcript levels of
      mitochondrial-encoded ATP synthase 6/8 were similarly upregulated in these
      tissues whereas transcript levels of the nuclear encoded subunits Cox4 and ATP
      synthase alpha did not change during hibernation. Immunoblot analysis revealed a
      2.4-fold increase in Cox 1 protein and a slight decrease in Cox 4 protein in
      kidney of hibernating squirrels, compared with euthermic controls. Hibernating
      mammals may increase the expression of the mitochondrial genome in general, and
      Cox1 specifically, to prevent or minimize the damage to the electron transport
      chain caused by the cold and ischemia experienced during a hibernation bout.

PMID- 12000808
TI  - Olfactory sensitivity for aliphatic alcohols in squirrel monkeys and pigtail
      macaques.
AB  - The view that primates are microsmatic animals is based mainly on an
      interpretation of neuroanatomical features, whereas physiological evidence of a
      poorly developed sense of smell in this order of mammals is largely lacking.
      Using a conditioning paradigm, we therefore assessed the olfactory sensitivity of
      three squirrel monkeys (Saimiri sciureus) and of four pigtail macaques (Macaca
      nemestrina) for a homologous series of aliphatic alcohols (ethanol to 1-octanol)
      and isomeric forms of some of these substances. In the majority of cases, the
      animals of both species significantly discriminated concentrations below 1 part
      per million from the odourless solvent, and with 1-hexanol individual monkeys
      even demonstrated thresholds below 10 parts per billion. The results showed (i)
      that both primate species have a well-developed olfactory sensitivity for
      aliphatic alcohols, which for the majority of substances matches or even is
      better than that of species such as the rat, (ii) that both species generally
      show very similar olfactory detection thresholds for aliphatic alcohols, and
      (iii) that a significant negative correlation between perceptibility in terms of
      olfactory detection threshold and carbon chain length of both the aliphatic 1-
      and 2-alcohols exists in both species. These findings support the idea that
      across-species comparisons of neuroanatomical features are a poor predictor of
      olfactory performance and that general labels such as 'microsmat' or 'macrosmat',
      which are usually based on allometric comparisons of olfactory brain structures,
      are inadequate to describe the olfactory capabilities of a species. Further, our
      findings suggest that olfaction may play an important and hitherto underestimated
      role in the regulation of behaviour in the species tested.

PMID- 12000809
TI  - Intracellular ion activities in Malpighian tubule cells of Rhodnius prolixus:
      evaluation of Na+-K+-2Cl- cotransport across the basolateral membrane.
AB  - Intracellular ion activities (a(ion)) and basolateral membrane potential (Vbl)
      were measured in Malpighian tubule cells of Rhodnius prolixus using double
      barrelled ion-selective microelectrodes. In saline containing 103 mmol l(-1) Na+,
      6 mmol l(-1) K+ and 93 mmol l(-1) Cl-, intracellular ion activities in
      unstimulated upper Malpighian tubules were 21, 86 and 32 mmol l(-1),
      respectively. In serotonin-stimulated tubules, aCl was unchanged, whereas aNa
      increased to 33 mmol l(-1) and aK declined to 71 mmol l(-1). Vbl was -59 mV and 
      63 mV for unstimulated and stimulated tubules, respectively. Calculated
      electrochemical potentials (deltamuF) favour passive movement of Na+ into the
      cell and passive movement of Cl- out of the cell in both unstimulated and
      serotonin-stimulated tubules. Passive movement of K+ out of the cell is favoured
      in unstimulated tubules. In stimulated tubules, deltamuF for K+ is close to 0 mV.
      The thermodynamic feasibilities of Na+-K+-2Cl-, Na+-Cl- and K+-Cl- cotransporters
      were evaluated by calculating the net electrochemical potential (deltamu(net)/F)
      for each transporter. Our results show that a Na+-K+-2Cl- or a Na+-Cl-
      cotransporter but not a K+-Cl- cotransporter would permit the movement of ions
      into the cell in stimulated tubules. The effects of Ba2+ and ouabain on Vbl and
      rates of fluid and ion secretion show that net entry of K+ through ion channels
      or the Na+/K+-ATPase can be ruled out in stimulated tubules. Maintenance of
      intracellular Cl- activity was dependent upon the presence of both Na+ and K+ in
      the bathing saline. Bumetanide reduced the fluxes of both Na+ and K+. Taken
      together, the results support the involvement of a basolateral Na+-K+-2Cl-
      cotransporter in serotonin-stimulated fluid secretion by Rhodnius prolixus
      Malpighian tubules.

PMID- 12000810
TI  - Fertilization ecology of egg coats: physical versus chemical contributions to
      fertilization success of free-spawned eggs.
AB  - Free-spawned eggs are typically enclosed within accessory structures that are
      shed early in development. Most research on the role of these structures in
      fertilization has focused on chemical constituents and their influence on sperm
      egg interaction. Here I test an alternative hypothesis that accessory structures
      play an important physical role in fertilization by increasing the size and
      buoyancy of the egg, making it a better target for sperm. In the sand dollar
      Dendraster excentricus, the jelly coat increases egg target size sixfold. At
      nonsaturating sperm concentrations, fertilization declined consistently following
      jelly coat removal by two independent methods. Regression analysis using a
      standard fertilization kinetics model found that 54-73% of this decline on
      average was predicted by changes in the rate of sperm-egg collision, resulting
      from changes in egg target size and density. Sperm swimming speed, a key
      parameter in the model, did not vary as a function of sperm concentration or
      exposure to egg-water. The organic cost of jelly is a fraction of that of the
      ovum, providing an efficient means of extending target size beyond the ovum size
      that is optimal for larval or juvenile development. These results support the
      hypothesis that physical attributes of jelly coats can account for a significant
      portion of their contribution to fertilization, and may help to explain why coats
      and other accessory structures are often substantially larger than expected from
      the nature of chemical interactions between egg and sperm.

PMID- 12000811
TI  - Respiratory adaptations in a deep-sea orbiniid polychaete from Gulf of Mexico
      brine pool NR-1: metabolic rates and hemoglobin structure/function relationships.
AB  - Methanoaricia dendrobranchiata Blake (Polychaeta; Orbiniidae) occurs in large
      numbers in association with communities of the mussel Bathymodiolus childressi at
      hydrocarbon seeps on the Louisiana Slope of the Gulf of Mexico. Its microhabitat
      can be strongly hypoxic (oxygen is often undetectable) and sulfidic (sulfide
      concentrations can reach millimolar levels), which may seriously challenge
      aerobic metabolism. We describe a suite of adaptations to its low-oxygen
      environment. The worms are capable of regulating their rate of oxygen consumption
      down to partial pressures of approximately 870 Pa oxygen. This capability
      correlates with a large gill surface area, a small diffusion distance from sea
      water to blood, a very high hemoglobin oxygen-affinity (P50=27.8 Pa at 10 degrees
      C and pH 7.6) and a Bohr effect that is pronounced at high oxygen saturations.
      When fully saturated, the hemoglobin binds sufficient oxygen for only 31 min of
      aerobic metabolism. However, these polychaetes can withstand extended periods of
      anoxia both in the absence and presence of 1 mmol l(-1) sulfide (TL50=approx. 5.5
      and 4 days, respectively).

PMID- 12000812
TI  - Tuberculosis--the global view.

PMID- 12000813
TI  - Immediate repair compared with surveillance of small abdominal aortic aneurysms.
AB  - BACKGROUND: Whether elective surgical repair of small abdominal aortic aneurysms
      improves survival remains controversial. METHODS: We randomly assigned patients
      50 to 79 years old with abdominal aortic aneurysms of 4.0 to 5.4 cm in diameter
      who did not have high surgical risk to undergo immediate open surgical repair of
      the aneurysm or to undergo surveillance by means of ultrasonography or computed
      tomography every six months with repair reserved for aneurysms that became
      symptomatic or enlarged to 5.5 cm. Follow-up ranged from 3.5 to 8.0 years (mean,
      4.9). RESULTS: A total of 569 patients were randomly assigned to immediate repair
      and 567 to surveillance. By the end of the study, aneurysm repair had been
      performed in 92.6 percent of the patients in the immediate-repair group and 61.6
      percent of those in the surveillance group. The rate of death from any cause, the
      primary outcome, was not significantly different in the two groups (relative risk
      in the immediate-repair group as compared with the surveillance group, 1.21; 95
      percent confidence interval, 0.95 to 1.54). Trends in survival did not favor
      immediate repair in any of the prespecified subgroups defined by age or diameter
      of aneurysm at entry. These findings were obtained despite a low total operative
      mortality of 2.7 percent in the immediate-repair group. There was also no
      reduction in the rate of death related to abdominal aortic aneurysm in the
      immediate-repair group (3.0 percent) as compared with the surveillance group (2.6
      percent). Eleven patients in the surveillance group had rupture of abdominal
      aortic aneurysms (0.6 percent per year), resulting in seven deaths. The rate of
      hospitalization related to abdominal aortic aneurysm was 39 percent lower in the
      surveillance group. CONCLUSIONS: Survival is not improved by elective repair of
      abdominal aortic aneurysms smaller than 5.5 cm, even when operative mortality is
      low.

PMID- 12000814
TI  - Long-term outcomes of immediate repair compared with surveillance of small
      abdominal aortic aneurysms.
AB  - BACKGROUND: Two clinical trials, one British and one American, have shown that
      early, prophylactic elective surgery does not improve five-year survival among
      patients with small abdominal aortic aneurysms. We report long-term outcomes in
      the United Kingdom Small Aneurysm Trial. METHODS: We randomly assigned 1090
      patients, 60 to 76 years of age, with small abdominal aortic aneurysms (diameter,
      4.0 to 5.5 cm) to one of two groups: 563 were assigned to undergo early elective
      surgery, and 527 were assigned to undergo surveillance by ultrasonography.
      Patients were followed in the trial until June 1998 and thereafter until August
      2001; the mean duration of follow-up was 8 years (range, 6 to 10). RESULTS: The
      mean duration of survival was 6.5 years among patients in the surveillance group,
      as compared with 6.7 years among patients in the early-surgery group (P=0.29).
      The adjusted hazard ratio for death from any cause in the early-surgery group as
      compared with the surveillance group was 0.83 (95 percent confidence interval,
      0.69 to 1.00; P=0.05). The 30-day operative mortality in the early-surgery group
      (5.5 percent) led to an early disadvantage in terms of survival. The survival
      curves crossed at three years, and at eight years, mortality in the early-surgery
      group was 7.2 percentage points lower than that in the surveillance group
      (P=0.03). There was no evidence that age, sex, or the initial size of the
      aneurysm modified the hazard ratio or that delayed surgery in the surveillance
      group increased 30-day postoperative mortality. Death was attributable to a
      ruptured aneurysm in 19 of the 411 men who died (5 percent) and in 12 of the 85
      women who died (14 percent) (P=0.001). The rate of early cessation of smoking was
      higher in the early-surgery group than in the surveillance group. CONCLUSIONS:
      Among patients with a small abdominal aortic aneurysm, we found no long-term
      difference in mean survival between the early-surgery and surveillance groups,
      although after eight years, total mortality was lower in the early-surgery group.
      This difference may be attributed in part to beneficial changes in lifestyle
      adopted by members of the early-surgery group.

PMID- 12000815
TI  - Changes in the transmission of tuberculosis in New York City from 1990 to 1999.
AB  - BACKGROUND: Over the past decade, there has been a reduction in the incidence of
      tuberculosis in New York City and in the United States. However, the reduction
      has been confined mainly to U.S.-born persons. Understanding the reasons for the
      lack of reduction among non-U.S.-born persons may lead to new strategies for
      tuberculosis control. METHODS: We performed DNA fingerprinting with the IS6110
      insertion sequence of the organisms isolated from patients with culture-positive
      tuberculosis in northern Manhattan from 1990 to 1999. The goal was to identify
      the strains responsible for multiple infections, presumably through recent
      transmission (clusters of cases), as well as the strains found in only one
      patient, presumably representing reactivation of latent infection. RESULTS: Of
      546 available isolates of Mycobacterium tuberculosis, 261 (48 percent) belonged
      to a cluster and 285 (52 percent) did not. In multivariate analysis, significant
      predictors of noncluster status included birth outside the United States (odds
      ratio for a strain causing a cluster among non-Hispanic foreign-born patients,
      0.31; 95 percent confidence interval, 0.14 to 0.66; odds ratio among Hispanic
      foreign-born patients, 0.51; 95 percent confidence interval, 0.30 to 0.88), age
      greater than 60 years (odds ratio, 0.37), and diagnosis after 1993 (odds ratio,
      0.50). All these characteristics appeared to be associated with reactivation
      disease rather than with tuberculosis due to recent transmission. Homelessness
      was associated with clustering (odds ratio, 1.78; 95 percent confidence interval,
      0.99 to 3.20) and therefore with recent transmission. CONCLUSIONS: These findings
      from northern Manhattan suggest that among foreign-born persons, tuberculosis is
      largely caused by reactivation of latent infection, whereas among U.S.-born
      persons, many cases result from recent transmission. Strategies for the control
      and elimination of tuberculosis among foreign-born persons at high risk should be
      directed toward the treatment of latent tuberculosis infection.

PMID- 12000817
TI  - Image in clinical medicine. Abdominal aortic aneurysm.

PMID- 12000816
TI  - Germ-line mutations in nonsyndromic pheochromocytoma.
AB  - BACKGROUND: The group of susceptibility genes for pheochromocytoma that included
      the proto-oncogene RET (associated with multiple endocrine neoplasia type 2 [MEN
      2]) and the tumor-suppressor gene VHL (associated with von Hippel-Lindau disease)
      now also encompasses the newly identified genes for succinate dehydrogenase
      subunit D (SDHD) and succinate dehydrogenase subunit B (SDHB), which predispose
      carriers to pheochromocytomas and glomus tumors. We used molecular tools to
      classify a large cohort of patients with pheochromocytoma with respect to the
      presence or absence of mutations of one of these four genes and to investigate
      the relevance of genetic analyses to clinical practice. METHODS: Peripheral blood
      from unrelated, consenting registry patients with pheochromocytoma was tested for
      mutations of RET, VHL, SDHD, and SDHB. Clinical data at first presentation and
      follow-up were evaluated. RESULTS: Among 271 patients who presented with
      nonsyndromic pheochromocytoma and without a family history of the disease, 66 (24
      percent) were found to have mutations (mean age, 25 years; 32 men and 34 women).
      Of these 66, 30 had mutations of VHL, 13 of RET, 11 of SDHD, and 12 of SDHB.
      Younger age, multifocal tumors, and extraadrenal tumors were significantly
      associated with the presence of a mutation. However, among the 66 patients who
      were positive for mutations, only 21 had multifocal pheochromocytoma. Twenty
      three (35 percent) presented after the age of 30 years, and 17 (8 percent) after
      the age of 40. Sixty-one (92 percent) of the patients with mutations were
      identified solely by molecular testing of VHL, RET, SDHD, and SDHB; these
      patients had no associated signs and symptoms at presentation. CONCLUSIONS:
      Almost one fourth of patients with apparently sporadic pheochromocytoma may be
      carriers of mutations; routine analysis for mutations of RET, VHL, SDHD, and SDHB
      is indicated to identify pheochromocytoma-associated syndromes that would
      otherwise be missed.

PMID- 12000818
TI  - Clinical practice. Aspirin for primary prevention of coronary events.

PMID- 12000819
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 14-2002. A 51-year-old woman with recurrent hemoptysis.

PMID- 12000820
TI  - Detection and management of small aortic aneurysms.

PMID- 12000821
TI  - Pheochromocytoma--death of an axiom.

PMID- 12000822
TI  - The Wendland case--withdrawing life support from incompetent patients who are not
      terminally ill.

PMID- 12000823
TI  - Post-traumatic stress disorder.

PMID- 12000824
TI  - Chemotherapy for lung cancer.

PMID- 12000825
TI  - Decisions about voriconazole versus liposomal amphotericin B.

PMID- 12000826
TI  - Mortality among patients admitted to hospitals on weekends as compared with
      weekdays.

PMID- 12000827
TI  - Transplacental transfer of small-cell carcinoma of the lung.

PMID- 12000828
TI  - New strategy for prenatal diagnosis of X-linked disorders.

PMID- 12000829
TI  - A novel type of uracil-DNA glycosylase mediating repair of hydrolytic DNA damage
      in the extremely thermophilic eubacterium Thermus thermophilus.
AB  - Spontaneous hydrolytic deamination of DNA cytosine and 5-methyl-cytosine residues
      is an abundant source of C/G (5-meC/G) to T/A transition mutations. As a result
      of this pressure, at least six different families of enzymes have evolved that
      initiate repair at U/G (T/G) mispairs, the relevant pre-mutagenic intermediates.
      The necessarily higher rate of the process at elevated temperatures must pose a
      correspondingly accentuated problem to contemporary thermophilic organisms and
      may have been a serious bottleneck in early evolution when life passed through a
      phase of very high ambient temperatures. Here we show that Thermus thermophilus,
      an aerobic, Gram-negative eubacterium thriving at up to 85 degrees C, harbors two
      uracil-DNA glycosylases (UDGs), termed TTUDGA and TTUDGB. According to both amino
      acid sequence and enzymatic properties, TTUDGA clearly belongs to the family of
      'thermostable UDGs'. TTUDGB shares with TTUDGA 23% sequence identity, but differs
      from it in profound functional aspects. TTUDGB, unlike TTUDGA, does not act upon
      uracil residues in the context of single-stranded DNA whereas both enzymes
      process various double-stranded substrates, albeit with different preferences.
      TTUDGB shows a number of sequence features characteristic of the UDG superfamily,
      but surprisingly lacks any polar residue within its so-called motif 1 (GLAPG
      X(10)-F). This finding is in conflict with a previously assumed crucial catalytic
      role of motif 1 in water activation and supports a more recently suggested
      alternative of a dissociative ('S(N)1-type') reaction mechanism. Together, the
      characteristics of TTUDGB and its homologs in other organisms define a novel
      family of UDG repair enzymes.

PMID- 12000830
TI  - Identification of essential domains for Escherichia coli tRNA(leu) aminoacylation
      and amino acid editing using minimalist RNA molecules.
AB  - Escherichia coli leucyl-tRNA synthetase (LeuRS) aminoacylates up to six different
      class II tRNA(leu) molecules. Each has a distinct anticodon and varied
      nucleotides in other regions of the tRNA. Attempts to construct a minihelix RNA
      that can be aminoacylated with leucine have been unsuccessful. Herein, we
      describe the smallest tRNA(leu) analog that has been aminoacylated to a
      significant extent to date. A series of tRNA(leu) analogs with various domains
      and combinations of domains deleted was constructed. The minimal RNA that was
      efficiently aminoacylated with LeuRS was one in which the anticodon stem-loop and
      variable arm stem-loop, but neither the D-arm nor T-arm, were deleted.
      Aminoacylation of this minimal RNA was abolished when the discriminator base A73
      was replaced with C73 or when putative tertiary interactions between the D-loop
      and T-loop were disrupted, suggesting that these identity elements are still
      functioning in the minimized RNA. The various constructs that were significantly
      aminoacylated were also tested for amino acid editing by the synthetase. The
      anticodon and variable stem-loop domains were also dispensable for hydrolysis of
      the charged tRNA(leu) mimics. These results suggest that LeuRS may rely on
      identity elements in overlapping domains of the tRNA for both its aminoacylation
      and editing activities.

PMID- 12000832
TI  - Reconstitution of the base excision repair pathway for 7,8-dihydro-8-oxoguanine
      with purified human proteins.
AB  - In mammalian cells, repair of the most abundant endogenous premutagenic lesion in
      DNA, 7,8-dihydro-8-oxoguanine (8-oxoG), is initiated by the bifunctional DNA
      glycosylase OGG1. By using purified human proteins, we have reconstituted repair
      of 8-oxoG lesions in DNA in vitro on a plasmid DNA substrate containing a single
      8-oxoG residue. It is shown that efficient and complete repair requires only
      hOGG1, the AP endonuclease HAP1, DNA polymerase (Pol) beta and DNA ligase I.
      After glycosylase base removal, repair occurred through the AP lyase step of
      hOGG1 followed by removal of the 3'-terminal sugar phosphate by the 3'-diesterase
      activity of HAP1. Addition of PCNA had a slight stimulatory effect on repair.
      Fen1 or high concentrations of Pol beta were required to induce strand
      displacement DNA synthesis at incised 8-oxoG in the absence of DNA ligase. Fen1
      induced Pol beta strand displacement DNA synthesis at HAP1-cleaved AP sites
      differently from that at gaps introduced by hOGG1/HAP1 at 8-oxoG sites. In the
      presence of DNA ligase I, the repair reaction at 8-oxoG was confined to 1 nt
      replacement, even in the presence of high levels of Pol beta and Fen1. Thus, the
      assembly of all the core proteins for 8-oxoG repair catalyses one major pathway
      that involves single nucleotide repair patches.

PMID- 12000831
TI  - Site-specific and temporally controlled initiation of DNA replication in a human
      cell-free system.
AB  - We have recently established a cell-free system from human cells that initiates
      semi-conservative DNA replication in nuclei isolated from cells which are
      synchronised in late G1 phase of the cell division cycle. We now investigate
      origin specificity of initiation using this system. New DNA replication foci are
      established upon incubation of late G1 phase nuclei in a cytosolic extract from
      proliferating human cells. The intranuclear sites of replication foci initiated
      in vitro coincide with the sites of earliest replicating DNA sequences, where DNA
      replication had been initiated in these nuclei in vivo upon entry into S phase of
      the previous cell cycle. In contrast, intranuclear sites that replicate later in
      S phase in vivo do not initiate in vitro. DNA replication initiates in this cell
      free system site-specifically at the lamin B2 DNA replication origin, which is
      also activated in vivo upon release of mimosine-arrested late G1 phase cells into
      early S phase. In contrast, in the later replicating ribosomal DNA locus (rDNA)
      we neither detected replicating rDNA in the human in vitro initiation system nor
      upon entry of intact mimosine-arrested cells into S phase in vivo. As a control,
      replicating rDNA was detected in vivo after progression into mid S phase. These
      data indicate that early origin activity is faithfully recapitulated in the in
      vitro system and that late origins are not activated under these conditions,
      suggesting that early and late origins may be subject to different mechanisms of
      control.

PMID- 12000833
TI  - Epstein-Barr virus nuclear antigen 5 inhibits pre-mRNA cleavage and
      polyadenylation.
AB  - The long-standing suspicion that Epstein-Barr virus nuclear antigen 5 (EBNA5) is
      involved in transcription regulation was recently confirmed by the observation by
      several groups that EBNA5 cooperates with EBNA2 in activation of the LMP1
      promoter. In attempts to elucidate the molecular basis for the EBNA5-mediated
      enhancement of EBNA2 transactivation, we obtained evidence of an additional
      function of EBNA5: at high but still biologically relevant levels, EBNA5 acted as
      a repressor of gene expression by interfering with the processing of pre-mRNA.
      Transient transfections with reporter plasmids revealed that EBNA5 repressed
      reporter mRNA and protein expression in the cytoplasm, but did not lower the
      steady-state level of reporter RNA in the total cellular RNA fraction. We have
      excluded that repression occurred as a consequence of cell death induced by
      EBNA5. Using the RNase protection assay with a probe comprising the pre-mRNA
      cleavage and polyadenylation site, EBNA5 was found to inhibit 3'-end cleavage and
      polyadenylation of pre-mRNAs from the reporter plasmids investigated. The effect
      of inhibitory levels of EBNA5 on chromosomal genes was examined in transient
      transfections by expression profiling using a cDNA microarray panel containing
      588 genes. The results showed that EBNA5 could also inhibit the expression of
      chromosomal genes and did it in a discriminatory manner. This is consistent with
      the notion that a regulatory mechanism exists in the cell that confers
      specificity to the selection by EBNA5 of target genes for repression.

PMID- 12000834
TI  - Functional characterisation of mycobacterial DNA gyrase: an efficient decatenase.
AB  - A rapid single step immunoaffinity purification procedure is described for
      Mycobacterium smegmatis DNA gyrase. The mycobacterial enzyme is a 340 kDa
      heterotetrameric protein comprising two subunits each of GyrA and GyrB,
      exhibiting subtle differences and similarities to the well-characterised
      Escherichia coli gyrase. In contrast to E.coli gyrase, the M.smegmatis enzyme
      exhibits strong decatenase activity at physiological Mg2+ concentrations.
      Further, the enzymes exhibited marked differences in ATPase activity, DNA binding
      characteristics and susceptibility to fluoroquinolones. The holoenzyme showed
      very low intrinsic ATPase activity and was stimulated 20-fold in the presence of
      DNA. The DNA-stimulated ATPase kinetics revealed apparent K0.5 and kcat of 0.68
      mM and 0.39 s(-1), respectively. The dissociation constant for DNA was found to
      be 9.2 nM, which is 20 times weaker than that of E.coli DNA gyrase. The
      differences between the enzymes were further substantiated as they exhibited
      varied sensitivity to moxifloxacin and ciprofloxacin. In spite of these
      differences, mycobacterial DNA gyrase is a functionally and mechanistically
      conserved enzyme and the variations in activity seem to reflect functional
      optimisation for its physiological role during mycobacterial genome replication.

PMID- 12000835
TI  - Unique condensation patterns of triplex DNA: physical aspects and physiological
      implications.
AB  - Triple-stranded DNA structures can be formed in living cells, either by native
      DNA sequences or following the application of antigene strategies, in which
      triplex-forming oligonucleotides are targeted to the nucleus. Recent studies
      imply that triplex motifs may play a role in DNA transcription, recombination and
      condensation processes in vivo. Here we show that very short triple-stranded DNA
      motifs, but not double-stranded segments of a comparable length, self-assemble
      into highly condensed and ordered structures. The condensation process, studied
      by circular dichroism and polarized-light microscopy, occurs under conditions
      that mimic cellular environments in terms of ionic strength, ionic composition
      and crowding. We argue that the unique tendency of triplex DNA structures to self
      assemble, a priori unexpected in light of the very short length and the large
      charge density of these motifs, reflects the presence of strong attractive
      interactions that result from enhanced ion correlations. The results provide, as
      such, a direct experimental link between charge density, attractive interactions
      between like-charge polymers and DNA packaging. Moreover, the observations
      strongly support the notion that triple-stranded DNA motifs may be involved in
      the regulation of chromosome organization in living cells.

PMID- 12000836
TI  - Minihelix-loop RNAs: minimal structures for aminoacylation catalysts.
AB  - We report here an in vitro selected ribozyme, KL17, which is active in charging
      amino acids on its own 5'-OH group. The ribozyme consists of two catalytic
      domains, one of which (consisting of P5/P6/L6) recognizes amino acid substrates
      based on the steric environment of the side chain, whereas the other recognizes
      an aminoacylated oligonucleotide. The secondary structure of this ambidextrous
      ribozyme arranges into a pseudoknot, where L6 docks onto the 3'-terminal single
      stranded region. The formation of this pseudoknot structure brings the P6 region,
      in which the essential catalytic core is most likely embedded, into the proximity
      of the 5'-OH group. Our studies show that the P6-L6 domain can be separated from
      the main body of KL17 and the derived P6-L6 minihelix-loop RNA can act as a trans
      aminoacylation catalyst. In this report, we also compare this ribozyme with an
      analogous aminoacylation system previously characterized in our laboratory and
      illuminate the similarities and differences between these catalytic systems.

PMID- 12000838
TI  - Thymine-methyl/pi interaction implicated in the sequence-dependent deformability
      of DNA.
AB  - The crystal structures of deoxy-oligonucleotides were retrieved from the Nucleic
      Acid Database and analyzed with the use of our program CHPI. The structure of 5'
      ApTpApT-3' has been shown to be stabilized by the 5-methyl group in the thymidine
      moiety that favorably interacts with the adenine pi-ring preceding it. H2' of the
      deoxyribose in adenine also interacts with the thymine ring next to it. Since a
      5'-ApT-3' sequence is accompanied by another 5'-ApT-3' in the complementary
      strand, the interaction is duplicated, thus forming a 'twin A/T-Me interaction'.
      Coordinates of oligonucleotides with A-T rich sequences were retrieved and
      analyzed. In almost every case, the thymidine 5-methyl group favorably interacts
      with an adenine ring in the same strand. The structure of duplexes incorporating
      A-tracts was also analyzed. The 5-methyl group in the thymidine moiety has been
      found to interact favorably with the base pi-ring before it. Since an A-tract is
      lined with an oligo-T sequence in the complementary strand, a successive N/T-Me
      stacking may contribute in making the A-tracts robust and straight. The possible
      involvement of the N/T-Me and the twin A/T-Me motif in the deformability of DNA
      has been suggested. The role of methyl groups in modified DNA has been discussed
      on a similar basis.

PMID- 12000837
TI  - Mammalian Rad51C contributes to DNA cross-link resistance, sister chromatid
      cohesion and genomic stability.
AB  - The eukaryotic Rad51 protein is a structural and functional homolog of
      Escherichia coli RecA with a role in DNA repair and genetic recombination. Five
      paralogs of Rad51 have been identified in vertebrates, Rad51B, Rad51C, Rad51D,
      Xrcc2 and Xrcc3, which are also implicated in recombination and genome stability.
      Here, we identify a mammalian cell mutant in Rad51C. We show that the Chinese
      hamster cell mutant, CL-V4B, has a defect in Rad51C. Sequencing of the hamster
      Rad51C cDNA revealed a 132 bp deletion corresponding to an alternatively spliced
      transcript with lack of exon 5. CL-V4B was hypersensitive to the interstrand
      cross-linking agents mitomycin C (MMC) and cisplatinum, the alkylating agent
      methyl methanesulfonate and the topoisomerase I inhibitor campthotecin and showed
      impaired Rad51 foci formation in response to DNA damage. The defect in Rad51C
      also resulted in an increase of spontaneous and MMC-induced chromosomal
      aberrations as well as a lack of induction of sister chromatid exchanges.
      However, centrosome formation was not affected. Intriguingly, a reduced level of
      sister chromatid cohesion was found in CL-V4B cells. These results reveal a role
      for Rad51C that is unique among the Rad51 paralogs.

PMID- 12000839
TI  - Defective nucleotide excision repair in yeast hpr1 and tho2 mutants.
AB  - Nucleotide excision repair (NER) and transcription are intimately related. First,
      TFIIH has a dual role in transcription initiation and NER and, secondly,
      transcription leads to more efficient repair of damage present in transcribed
      sequences. It is thought that elongating RNAPII, stalled at a DNA lesion, is used
      for the loading of the NER machinery in a process termed transcription-coupled
      repair (TCR). Non-transcribed regions are repaired by the so-called global genome
      repair (GGR). We have previously defined a number of yeast genes, whose deletions
      confer transcription-dependent hyper-recombination phenotypes. As these mutations
      cause impairment of transcription elongation we have assayed whether they also
      affect DNA repair. We show that null mutations of the HPR1 and THO2 genes,
      encoding two prominent proteins of the THO complex, increase UV sensitivity of
      yeast cells lacking GGR. Consistent with this result, molecular analyses of DNA
      repair of the RPB2 transcribed strand using T4 endo V show that hpr1 and tho2 do
      indeed impair TCR. However, this effect is not confined to TCR alone because the
      mutants are slightly affected in GGR. These results indicate that THO affects
      both transcription and NER. We discuss different alternatives to explain the
      effect of the THO complex on DNA repair.

PMID- 12000840
TI  - HuD binds to three AU-rich sequences in the 3'-UTR of neuroserpin mRNA and
      promotes the accumulation of neuroserpin mRNA and protein.
AB  - Neuroserpin is an axonally secreted serine protease inhibitor expressed in the
      nervous system that protects neurons from ischemia-induced apoptosis. Mutant
      neuroserpin forms have been found polymerized in inclusion bodies in a familial
      autosomal encephalopathy causing dementia, or associated with epilepsy.
      Regulation of neuroserpin expression is mostly unknown. Here we demonstrate that
      neuroserpin mRNA and the RNA-binding protein HuD are co-expressed in the rat
      central nervous system, and that HuD binds neuroserpin mRNA in vitro with high
      affinity. Gel-shift, supershift and T1 RNase assays revealed three HuD-binding
      sequences in the 3'-untranslated region (3'-UTR) of neuroserpin mRNA. They are AU
      rich and 20, 51 and 19 nt in length. HuD binding to neuroserpin mRNA was also
      demonstrated in extracts of PC12 pheochromocytoma cells. Additionally, ectopic
      expression of increasing amounts of HuD in these cells results in the
      accumulation of neuroserpin 3'-UTR mRNA. Furthermore, stably transfected PC12
      cells over-expressing HuD contain increased levels of both neuroserpin mRNAs (3.0
      and 1.6 kb) and protein. Our results indicate that HuD stabilizes neuroserpin
      mRNA by binding to specific AU-rich sequences in its 3'-UTR, which prolongs the
      mRNA lifetime and increases protein level.

PMID- 12000841
TI  - Connected gene neighborhoods in prokaryotic genomes.
AB  - A computational method was developed for delineating connected gene neighborhoods
      in bacterial and archaeal genomes. These gene neighborhoods are not typically
      present, in their entirety, in any single genome, but are held together by
      overlapping, partially conserved gene arrays. The procedure was applied to
      comparing the orders of orthologous genes, which were extracted from the database
      of Clusters of Orthologous Groups of proteins (COGs), in 31 prokaryotic genomes
      and resulted in the identification of 188 clusters of gene arrays, which included
      1001 of 2890 COGs. These clusters were projected onto actual genomes to produce
      extended neighborhoods including additional genes, which are adjacent to the
      genes from the clusters and are transcribed in the same direction, which resulted
      in a total of 2387 COGs being included in the neighborhoods. Most of the
      neighborhoods consist predominantly of genes united by a coherent functional
      theme, but also include a minority of genes without an obvious functional
      connection to the main theme. We hypothesize that although some of the latter
      genes might have unsuspected roles, others are maintained within gene arrays
      because of the advantage of expression at a level that is typical of the given
      neighborhood. We designate this phenomenon 'genomic hitchhiking'. The largest
      neighborhood includes 79 genes (COGs) and consists of overlapping, rearranged
      ribosomal protein superoperons; apparent genome hitchhiking is particularly
      typical of this neighborhood and other neighborhoods that consist of genes coding
      for translation machinery components. Several neighborhoods involve previously
      undetected connections between genes, allowing new functional predictions. Gene
      neighborhoods appear to evolve via complex rearrangement, with different
      combinations of genes from a neighborhood fixed in different lineages.

PMID- 12000842
TI  - Transcripts of developmentally regulated Plasmodium falciparum genes quantified
      by real-time RT-PCR.
AB  - Plasmodium falciparum intraerythrocytic development is a complex process.
      Development proceeds rapidly from the trophozoite phase of nutrient acquisition
      and growth through to the synthetic and reproductive schizont phase, which ends
      with production of new invasive merozoites. During this process, the malaria
      parasite must express a series of different gene products, depending on its
      metabolic and synthetic needs. We are particularly interested in the development
      of the merozoite's organelles in the apical complex, which form during the later
      schizont stages. We have used quantitative real-time RT-PCR fluorogenic 5'
      nuclease assays (TaqMan) for the first time on malaria parasites for analysis of
      erythrocytic stage-specific gene expression. We analyzed transcripts of the
      P.falciparum eba-175 and other erythrocyte binding-like (ebl) family genes in
      temperature-synchronized parasites and found ebl genes have tightly controlled,
      stage-specific transcription. As expected, eba-175 transcripts were abundant only
      at the end of schizont development in a pattern most common among ebl, including
      baebl, pebl and jesebl. The maebl transcript pattern was unique, peaking at mid
      late trophozoite stage, but absent in late-stage schizonts. ebl-1 demonstrated
      another pattern of expression, which peaked during mid-schizont stage and then
      significantly diminished in late-stage schizonts. Our analysis demonstrates that
      using real-time RT-PCR fluorogenic 5' nuclease assays is a sensitive,
      quantitative method for analysis of Plasmodium transcripts.

PMID- 12000844
TI  - M-DNA is stabilised in G*C tracts or by incorporation of 5-fluorouracil.
AB  - M-DNA is a complex between the divalent metal ions Zn2+, Ni2+ and Co2+ and duplex
      DNA which forms at a pH of approximately 8.5. The stability and formation of M
      DNA was monitored with an ethidium fluorescence assay in order to assess the
      relationship between pH, metal ion concentration, DNA concentration and the base
      composition. The dismutation of calf thymus DNA exhibits hysteresis with the
      formation of M-DNA occurring at a higher pH than the reconversion of M-DNA back
      to B-DNA. Hysteresis is most prominent with the Ni form of M-DNA where complete
      reconversion to B-DNA takes several hours even in the presence of EDTA.
      Increasing the DNA concentration leads to an increase in the metal ion
      concentration required for M-DNA formation. Both poly(dG)*poly(dC) and
      poly(dA)*poly(dT) formed M-DNA more readily than the corresponding mixed sequence
      DNAs. For poly(dG)*(poly(dC) M-DNA formation was observed at pH 7.4 with 0.5 mM
      ZnCl2. Modified bases were incorporated into a 500 bp fragment of phage lambda
      DNA by polymerase chain reaction. DNAs in which guanine was replaced with
      hypoxanthine or thymine with 5-fluorouracil formed M-DNA at pHs below 8 whereas
      substitutions such as 2-aminoadenine and 5-methylcytosine had little effect.
      Poly[d(A5FU)] also formed a very stable M-DNA duplex as judged from T(m)
      measurements. It is evident that the lower the pK(a) of the imino proton of the
      base, the lower the pH at which M-DNA will form; a finding that is consistent
      with the replacement of the imino proton with the metal ion.

PMID- 12000843
TI  - Identification of delta helicase as the bovine homolog of HUPF1: demonstration of
      an interaction with the third subunit of DNA polymerase delta.
AB  - Delta helicase is a 5' to 3' DNA helicase that partially co-purifies with DNA
      polymerase delta (pol delta) from fetal bovine thymus tissue. We describe the
      resolution of delta helicase from pol delta on heparin-agarose chromatography and
      its purification to apparent homogeneity by affinity purification on single
      stranded DNA-cellulose chromatography, unique-sequence RNA-agarose
      chromatography, and ceramic hydroxyapatite chromatography. Delta helicase
      isolated from fetal bovine thymus had an apparent M(r) of 115 kDa in SDS-PAGE,
      and photo-crosslinked to [alpha-32P]ATP. Tandem mass spectrometry peptide mass
      data derived from the bovine polypeptide matched to human UPF1 (HUPF1), a 5' to
      3' RNA and DNA helicase, and a requisite component of the mRNA surveillance
      complex. Antisera against HUPF1 cross-reacted with delta helicase on western
      analysis, and delta helicase activity was immunoinactivated by pre-incubation
      with antibodies to HUPF1, suggesting that delta helicase is the bovine homolog of
      HUPF1. Immunoprecipitation experiments demonstrated that HUPF1 interacts with the
      66-kDa third subunit of pol delta in vivo.

PMID- 12000845
TI  - Identification of nucleolin and nucleophosmin as genotoxic stress-responsive RNA
      binding proteins.
AB  - Genotoxic stress (DNA damage) can elicit multiple responses in mammalian cells,
      including the activation of numerous cascades of signal transduction that result
      in the activation of cellular genes involved in growth control, DNA repair and
      apoptosis. In an earlier report, we have shown that DNA-damaging agents can also
      induce the RNA-binding activity of several specific proteins that favor a double
      stem-loop RNA structure. Here we report the purification and identification of
      nucleophosmin (NPM) and nucleolin as two genotoxic stress-responsive RNA-binding
      proteins. UV radiation induces the protein expression levels and RNA-binding
      activity of NPM while nucleolin RNA-binding activity increases after UV or
      ionizing radiation exposure. Moreover, we have identified 40 mRNA ligands that
      are potentially regulated by nucleolin, several of which are stress-responsive
      transcripts. In addition, our data indicate that activation of nucleolin RNA
      binding activity by genotoxic stress is mediated by stress-activated protein
      kinase p38. Our findings suggest that activation of the RNA-binding properties of
      nucleolin and NPM is part of the cellular response to genotoxic stress.

PMID- 12000846
TI  - A reliable and efficient method for deleting operational sequences in PACs and
      BACs.
AB  - P1-derived artificial chromosomes (PACs) and bacterial artificial chromosomes
      (BACs) have become very useful as tools to study gene expression and regulation
      in cells and in transgenic mice. They carry large fragments of genomic DNA (> or
      =100 kb) and therefore may contain all of the cis-regulatory elements required
      for expression of a gene. Because of this, even when inserted randomly in the
      genome, they can emulate the native environment of a gene resulting in a tightly
      regulated pattern of expression. Because these large genomic clones often contain
      DNA sequences which can manipulate chromatin at the local level, they become
      immune to position effects which affect expression of smaller transgenes, and
      thus their expression is proportional to copy number. Transgenic mice containing
      large BACs and PACs have become excellent models to examine the regulation of
      gene expression. Their usefulness would certainly be increased if easy and
      efficient methods are developed to manipulate them. We describe herein a method
      to make deletion mutations reliably and efficiently using a novel modification of
      the Chi-stimulated homologous recombination method. Specifically, we generated
      and employed a Lox511 'floxed' CAM resistance marker that first affords selection
      for homologous recombination in Escherichia coli, and then can be easily deleted
      leaving only a single Lox511 site as the footprint.

PMID- 12000847
TI  - Commonly conserved genetic fragments revealed by genome profiling can serve as
      tracers of evolution.
AB  - We developed a method to produce, identify and analyze DNA fragments for the
      purpose of taxonomic classification. Genome profiling (GP) is a strategy that
      identifies genomic DNA fragments common to closely related species without prior
      knowledge of the DNA sequence. Random PCR, one of the key technologies of GP, is
      used to produce fragments and may be used even when there are mutations at the
      priming site. These fragments can then be distinguished based on the information
      of mobility and melting pattern when subjected to temperature gradient gel
      electrophoresis (TGGE). Corresponding fragments among several species, designated
      as commonly conserved genetic fragments (CCGFs), likely have the same genetic
      origin or correspond to the same gene. The criteria for identification of CCGFs
      has been defined and presented here. To assess this prediction, some of the
      fragments were sequenced and were confirmed to be CCGFs. We show that genome
      profiles bearing evolutionarily conserved CCGFs can be used to classify organisms
      and trace evolutionary pathways, among other profound applications.

PMID- 12000848
TI  - DNAWorks: an automated method for designing oligonucleotides for PCR-based gene
      synthesis.
AB  - The availability of sequences of entire genomes has dramatically increased the
      number of protein targets, many of which will need to be overexpressed in cells
      other than the original source of DNA. Gene synthesis often provides a fast and
      economically efficient approach. The synthetic gene can be optimized for
      expression and constructed for easy mutational manipulation without regard to the
      parent genome. Yet design and construction of synthetic genes, especially those
      coding for large proteins, can be a slow, difficult and confusing process. We
      have written a computer program that automates the design of oligonucleotides for
      gene synthesis. Our program requires simple input information, i.e. amino acid
      sequence of the target protein and melting temperature (needed for the gene
      assembly) of synthetic oligonucleotides. The program outputs a series of
      oligonucleotide sequences with codons optimized for expression in an organism of
      choice. Those oligonucleotides are characterized by highly homogeneous melting
      temperatures and a minimized tendency for hairpin formation. With the help of
      this program and a two-step PCR method, we have successfully constructed numerous
      synthetic genes, ranging from 139 to 1042 bp. The approach presented here
      simplifies the production of proteins from a wide variety of organisms for
      genomics-based studies.

PMID- 12000849
TI  - Combining chromatin immunoprecipitation and DNA footprinting: a novel method to
      analyze protein-DNA interactions in vivo.
AB  - A variety of methods are available to analyze protein-DNA interactions in vivo.
      Two of the most prominent of these methods are chromatin immunoprecipitation
      (ChIP) and in vivo footprinting. Both of these procedures have specific
      limitations. For example, the ChIP assay fails to document where exactly a
      protein binds in vivo. The precipitation of a specific segment of DNA with
      antibodies directed against DNA-binding proteins does not necessarily indicate
      that the protein directly interacts with a sequence in the precipitate but could
      rather reflect protein-protein interactions. Furthermore, the results of in vivo
      footprinting studies are inconclusive if a DNA sequence is analyzed that is bound
      by a specific protein in only a certain fraction of cells. Finally, in vivo
      footprinting does not indicate which protein is bound at a specific site. We have
      developed a new procedure that combines the ChIP assay and DMS footprinting
      techniques. Using this method we show here that antibodies specific for USF1 and
      NF-E2 precipitate the murine beta-globin promoter in MEL cells. DMS footprinting
      analysis of the DNA precipitated with NF-E2 antibodies revealed a protection over
      a partial NF-E2-binding site in the beta-globin downstream promoter region. We
      believe that this novel method will generally benefit investigators interested in
      analyzing protein-DNA interactions in vivo.

PMID- 12000850
TI  - High affinity nucleic acid aptamers for streptavidin incorporated into bi
      specific capture ligands.
AB  - We have isolated 2'-Fluoro-substituted RNA aptamers that bind to streptavidin
      (SA) with an affinity around 7 +/- 1.8 nM, comparable with that of recently
      described peptide aptamers. Binding to SA was not prevented by prior saturation
      with biotin, enabling nucleic acid aptamers to form useful ternary complexes.
      Mutagenesis, secondary structure analysis, ribonuclease footprinting and deletion
      analysis provided evidence for the essential structural features of SA-binding
      aptamers. In order to provide a general method for the exploitation of these
      aptamers, we produced derivatives in which they were fused to the naturally
      structured RNA elements, CopT or CopA. In parallel, we produced derivatives of
      CD4-binding aptamers fused to the complementary CopA or CopT elements. When
      mixed, these two chimeric aptamers rapidly hybridized, by virtue of CopA-CopT
      complementarity, to form stable, bi-functional aptamers that we called
      'adaptamers'. We show that a CD4-SA-binding adaptamer can be used to capture CD4
      onto a SA-derivatized surface, illustrating their general utility as indirect
      affinity ligands.

PMID- 12000851
TI  - RNA interference in mammalian cells using siRNAs synthesized with T7 RNA
      polymerase.
AB  - Methods that allow the specific silencing of a desired gene are invaluable tools
      for research. One of these is based on RNA interference (RNAi), a process by
      which double-stranded RNA (dsRNA) specifically suppresses the expression of a
      target mRNA. Recently, it has been reported that RNAi also works in mammalian
      cells if small interfering RNAs (siRNAs) are used to avoid activation of the
      interferon system by long dsRNA. Thus, RNAi could become a major tool for reverse
      genetics in mammalian systems. However, the high cost and the limited
      availability of the short synthetic RNAs and the lack of certainty that a
      designed siRNA will work present major drawbacks of the siRNA technology. Here we
      present an alternative method to obtain cheap and large amounts of siRNAs using
      T7 RNA polymerase. With multiple transfection procedures, including calcium
      phosphate co-precipitation, we demonstrate silencing of both exogenous and
      endogenous genes.

PMID- 12000852
TI  - Telomere measurement by quantitative PCR.
AB  - It has long been presumed impossible to measure telomeres in vertebrate DNA by
      PCR amplification with oligonucleotide primers designed to hybridize to the
      TTAGGG and CCCTAA repeats, because only primer dimer-derived products are
      expected. Here we present a primer pair that eliminates this problem, allowing
      simple and rapid measurement of telomeres in a closed tube, fluorescence-based
      assay. This assay will facilitate investigations of the biology of telomeres and
      the roles they play in the molecular pathophysiology of diseases and aging.

PMID- 12000853
TI  - Accuracy and calibration of commercial oligonucleotide and custom cDNA
      microarrays.
AB  - We compared the accuracy of microarray measurements obtained with oligonucleotide
      arrays (GeneChip, Affymetrix) with a laboratory-developed cDNA array by assaying
      test RNA samples from an experiment using a paradigm known to regulate many genes
      measured on both arrays. We selected 47 genes represented on both arrays,
      including both known regulated and unregulated transcripts, and established
      reference relative expression measurements for these genes in the test RNA
      samples using quantitative reverse transcriptase real-time PCR (QRTPCR) assays.
      The validity of the reproducible (average coefficient of variation = 11.8%)
      QRTPCR measurements were established through application of a new mathematical
      model. The performance of both array platforms in identifying regulated and non
      regulated genes was identical. With either platform, 16 of 17 definitely
      regulated genes were correctly identified, and no definitely unregulated
      transcript was falsely identified as regulated. Accuracy of the fold-change
      measurements obtained with each platform was assessed by determining measurement
      bias. Both platforms consistently underestimate the relative changes in mRNA
      expression between experimental and control samples. The bias observed with cDNA
      arrays was predictable for fold-changes <250-fold by QRTPCR and could be
      corrected by the calibration function F(c) = F(a(cDNA))(q), where F(a(cDNA)) is
      the microarray-determined fold-change comparing experimental with control
      samples, q is the correction factor and F(c) is the calibrated value. The bias
      observed with the commercial oligonucleotide arrays was less predictable and
      calibration was unfeasible. Following calibration, fold-change measurements
      generated by custom cDNA arrays were more accurate than those obtained by
      commercial oligonucleotide arrays. Our study demonstrates systematic bias of
      microarray measurements and identifies a calibration function that improves the
      accuracy of cDNA array data.

PMID- 12000854
TI  - Historical view of the influences of measurement and reading theories on the
      assessment of reading.
AB  - The purpose of this study is to briefly explore the interactions among
      measurement theories, reading theories, and measurement practices from an
      historical perspective. The assessment of reading provides a useful framework for
      examining how theories influence, and in some cases fail to influence, the
      practice of reading assessment as operationalized in reading tests. The first
      section describes a conceptual framework for examining the assessment of reading.
      Next I describe the major research traditions in measurement theory that have
      dominated measurement practice during the 20th century. In the next section I
      briefly introduce major reading theories. Next, I bring together the previous two
      sections in order to examine the adequacy of the proposed conceptual framework
      for examining the assessment of reading. This section includes criticism of
      measurement theory by selected reading theorists. It also provides a brief
      history of the use of Rasch measurement theory to calibrate reading tests.
      Finally, the main points of the study are summarized and discussed. It should be
      recognized that this study represents a preliminary analysis of these issues.

PMID- 12000855
TI  - The assessment of unidimensionality of normal and lognormal data: a look at two
      nonparametric procedures.
AB  - In this Monte Carlo study, the Type I error rate and the power of the Stout T
      procedure (DIMTEST) and the Holland-Rosenbaum procedure (HR) were examined for
      normal and lognormal data sets. Both procedures are based on a nonparametric item
      response model, where the key assumption is the item response function is
      monotonically nondecreasing. The two procedures performed adequately under
      certain conditions for both normal and lognormal data sets. Of the two, however,
      the Stout T procedure showed adequate power under more conditions than the
      Holland-Rosenbaum procedure.

PMID- 12000856
TI  - Rasch measurement in the Assessment of Growth Hormone Deficiency in adult
      patients.
AB  - The Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire was
      previously designed, translated and validated in several European countries to
      evaluate the impact of the disease on Quality of Life. This study aimed to test
      the metric properties of the Spanish version by means of Rasch analysis. A sample
      of 356 consecutive adult patients with untreated GHD was included in the study.
      Patients responded to the questionnaire at baseline and 12 months apart. Answers
      were analyzed following the dichotomous logistic response model. Parameter
      estimates, model-data fit and separation statistics were computed. The invariance
      of the item parameters across time was tested in the follow-up. Rasch results
      were additionally employed to ascertain score changes through the calculation of
      the Reliable Change Index (RCI). Items varied in severity from 8.3 -16.8 units
      (SE= 0.4-0.5) and fit to define a unidimensional variable. The item separation
      index (SI)(5.2) indicates a good and reliable (0.9) separation of items along the
      variable that they define. Moreover, results showed the AGHDA conforms to the
      model expectation of item parameter invariance between administrations. The
      substantial (2.3) and reliable (0.8) person SI also suggests the sample was well
      targeted by the questionnaire. According to the RCI, 84% of the patients did not
      show a significant transition in their measures. Results denote the items of the
      AGHDA succeeded in defining a scale characterized by the interval-level of its
      measures, suggesting the questionnaire could be a useful complement of the
      clinical evaluation of GHD patients at both group and individual level.

PMID- 12000857
TI  - An investigation of gender differences in the components influencing the
      difficulty of spatial ability items.
AB  - This study examines the role that gender differences play in the determination of
      the components influencing the difficulty of spatial ability items. Considerable
      research has examined the role of gender differences in spatial abilities, with
      sometimes contradictory findings. In general, the findings show that males tend
      to outperform females on spatial ability items. Other research has focused on
      determining the components of items that contribute to their difficulty. This
      research has usually been based on mixed-gender populations, however. The present
      study attempts to determine if gender influences the extent to which different
      components contribute to the difficulty of items. The results indicate that
      component difficulties show very little variation across gender. This finding
      supports the notion that any differences in raw scores observed for males and
      females are not due to differences in the manner in which males and females
      process spatial information or solve spatial ability items.

PMID- 12000858
TI  - Partial credit model and pivot anchoring.
AB  - This article contains information on the Rasch measurement partial credit model:
      what it is, how it differs from other Rasch models, when to use it, and how to
      use it. The calibration of instruments with increasingly complex items is
      described, starting with dichotomous items and moving on to polychotomous items
      using a single rating scale, and mixed polychotomous items using multiple rating
      scales, and instruments in which each item has its own rating scale. It also
      introduces a procedure for aligning rating scale categories to be used when more
      than one rating scale is used in a single instrument. Pivot anchoring is defined
      and an illustration of its use with the mental health scale of the SF-36 that
      contains positive and negative worded items is provided. It finally describes the
      effect of pivot anchoring on step calibrations, the item hierarchy, and person
      measures.

PMID- 12000859
TI  - Tocolysis: an update for the practitioner.

PMID- 12000860
TI  - The immunotherapy of patients with ovarian cancer.
AB  - Ovarian cancer is a leading cause of cancer mortality. Chemotherapy is effective
      in reducing tumor burden in a majority of patients, however, only approximately
      20% of advanced disease patients will ultimately survive tumor free, and further
      treatment options are needed. Continuing advances in immunology make
      immunotherapy a promising area for future research. The design of immunotherapy
      strategies for ovarian cancer requires an understanding of the immune
      microenvironment of the peritoneal cavity, which is frequently involved with
      ovarian cancer metastases and is the site of its most devastating effects.
      Immunotherapy approaches for ovarian cancer include locoregional and systemic
      cytokine therapies, prophylactic and therapeutic vaccines, and adoptive
      immunotherapy strategies. This review will summarize previous clinical trials as
      well as future directions for research. Further progress in T-cell specific
      immune responses will require the identification of specific ovarian cancer
      antigens that are processed and presented on the surface of tumor cells in the
      context of specific HLA molecules. In addition, a more detailed understanding of
      functional relations between the peritoneal microenvironment and the metastatic
      process is required.

PMID- 12000861
TI  - Do CD4+ CD25+ immunoregulatory T cells hinder tumor immunotherapy?
AB  - After years of banishment from mainstream immunology, the notion that one subset
      of T cells can exert regulatory effects on other T lymphocytes is back in
      fashion. Recent work in knockout and transgenic mice has begun to bring molecular
      definition to our understanding of immunoregulatory CD4+CD25+ T cells
      (Treg/Th3/Tr1). The identification of the glucocorticoid-induced tumor necrosis
      factor receptor family-related gene (GITR, also known as TNFRSF18) expressed on T
      regulatory cells might afford new therapeutic opportunities. Another possible
      therapeutic intervention could be the blockade of signaling through the molecular
      pair of tumor necrosis factor-related activation induced cytokine (TRANCE) and
      receptor activator of NF-kappaB (RANK). Based on the available evidence from
      experimental mouse tumor models, however, it seems that simply blocking or even
      eliminating T regulatory function will not be enough to manage established
      tumors. The challenge for immunotherapists now is to overcome immunosuppression
      using the knowledge gained through the understanding of T regulatory cell
      function.

PMID- 12000862
TI  - Depletion of CD4+ CD25+ regulatory cells augments the generation of specific
      immune T cells in tumor-draining lymph nodes.
AB  - Recent studies have identified a unique population of CD4+CD25+ regulatory T
      cells that is crucial for the prevention of spontaneous autoimmune diseases.
      Further studies demonstrated that depletion of CD4+CD25+ T cells enhances immune
      responses to nonself antigens. Because immune responses to malignant tumors are
      weak and ineffective, depletion of regulatory T cells has been reported to result
      in tumor regression. In the current study, using the weakly immunogenic MCA205
      sarcoma and the poorly immunogenic B16/BL6/D5 (D5) melanoma, depletion of
      CD4+CD25+ T cells by the administration of anti-CD25 monoclonal antibodies (mAb),
      PC61 induced some tumor growth retardation, but all mice eventually succumbed to
      tumors. In our laboratory, immunotherapy by the transfer of tumor-immune T cells
      has demonstrated potent antitumor effects. A reliable source of tumor-reactive T
      cells has been lymph nodes (LN) draining progressive tumors. Therapeutic effector
      T cells can be generated by in vitro activation of draining LN cells with anti
      CD3 mAb followed by culture in interleukin-2. In this system, PC61 mAb depletion
      of CD4+CD25+ T cells before or on day 8 of tumor growth resulted in increased
      sensitization in the draining LN. The therapeutic efficacy of activated tumor
      draining LN cells from mAb depleted mice increased approximately three fold while
      maintaining specificity when tested in adoptive immunotherapy of established
      pulmonary metastases. Specific interferon-gamma secretion by LN T cells from mice
      treated with PC61 mAb 1 day before tumor inoculation increased significantly.
      However, this increase was not demonstrated with LN T cells from mice treated on
      day 8 despite their enhanced therapeutic reactivities. Our results indicate that
      although the antitumor immunity enhanced by the depletion of CD4+CD25+ T cells is
      insufficient to eradicate tumors, it augments the sensitization of immune T cells
      in the draining LN, thus, facilitating adoptive immunotherapy.

PMID- 12000863
TI  - Antitumor effects in mice of the intravenous injection of attenuated Salmonella
      typhimurium.
AB  - Salmonella typhimurium genetically modified at the purI and msbB genes to
      increase dependence on adenine and decrease stimulation of tumor necrosis factor
      alpha production were injected intravenously into C57BL/6 mice bearing
      subcutaneous tumor or lung metastases. Decreased tumor growth and prolonged
      survival were seen in some, but not all of nine transplantable tumors. Salmonella
      increased in number in the tumor and reached levels 10,000 times higher than in
      the normal liver reservoir of these bacteria. Histologic studies revealed
      Salmonella growth in areas of the tumor although, in all cases, a viable rim of
      tumor survived and ultimately resulted in progressive tumor growth in all mice.
      These studies demonstrate that Salmonella can localize to transplantable murine
      tumors and partially inhibit tumor growth; however, additional modifications of
      the bacteria may be necessary if this approach is to develop into an effective
      treatment for patients with cancer.

PMID- 12000864
TI  - Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric
      oxide.
AB  - Dendritic cells (DC) are potent antigen-presenting cells that are important for
      the priming of antitumor cytotoxic T cells. Recent reports suggest that DC may
      also have direct cytotoxic effector functions against selected tumor-cell lines
      by mechanisms that are dependent on dendritic cell-tumor cell contact in vitro.
      The authors report that ex vivo-generated murine DC induce the apoptosis of a
      panel of syngeneic and allogeneic murine tumors. Apoptosis of the MCA205
      fibrosarcoma tumor-cell line by C57BL/6-derived DC was not mediated by Fas/FasL
      interactions and, in contrast to other studies, DC-tumor cell contact was not
      required to effect tumor-cell killing by DC. Therefore, the authors postulated
      that tumor-cell killing was mediated by an apoptotic factor that was secreted by
      DC. Even though DC did not secrete such apoptotic cytokines as interferon-alpha
      or tumor necrosis factor-alpha, they did secrete nitric oxide, and tumor
      apoptosis was partially abrogated by the nitric oxide synthase antagonist NG
      monomethyl-L-arginine. Therefore, the authors' data demonstrate a novel mechanism
      for DC-induced tumor-cell apoptosis that does not require DC-tumor cell contact
      and is partially mediated by nitric oxide.

PMID- 12000865
TI  - A gene encoding human gastric signet ring cell carcinoma antigen recognized by
      HLA-A31-restricted cytotoxic T lymphocytes.
AB  - SUMMARY: We previously reported acid-extracted natural antigenic peptide (F4.2
      [YSWMDISCWI]) of a gastric signet ring cell carcinoma HST-2 cells, recognized by
      HLA-A*31012-restricted autologous cytotoxic T lymphocytes, TcHST-2 line. In this
      study, the full-length cDNA (1101 bp), termed c98, predicting a protein composed
      of 170 amino acids was obtained. Because TcHST-2 cells could lyse the HLA-A31
      antigen (+) allogeneic tumor cells that were introduced with c98 gene, this gene
      was suggested to possess antigenicity. Beginning at N-terminal 61 amino acid, the
      N-terminal six amino acid sequence that is completely identical to F4.2 was
      present in c98; however, a sequence of four amino acids in C-terminal was not
      found. Nevertheless, this peptide, c98(61-70), seemed to be immunogenic, because
      cells pulsed with c98(61-70) peptide were lysed in a dose-dependent manner by
      TcHST-2 cells. The c98 gene was expressed ubiquitously in tumor cells as well as
      in normal tissues. However, some tumor cells, including HST-2 cells, expressed
      this antigen in a high content, and such cells were lysed by TcHST-2 cells in the
      context of HLA-A31 antigen. However, TcHST-2 cells did not lyse cells that
      expressed lower amounts of c98 than HST-2 cells. These data suggested that c98
      gene product and/or c98(61-70) peptides could be used as a candidate for tumor
      vaccines in cancer immunotherapy.

PMID- 12000866
TI  - A phase I study of nonmyeloablative chemotherapy and adoptive transfer of
      autologous tumor antigen-specific T lymphocytes in patients with metastatic
      melanoma.
AB  - This report describes a phase I clinical trial using nonmyeloablative, lympho
      depleting chemotherapy in combination with adoptive immunotherapy in patients
      with metastatic melanoma. The chemotherapy-conditioning schedule that induced
      transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2
      days) followed by fludarabine (25 mg/m(2) per day for 5 days). Immunotherapy for
      all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell
      clones selected for high avidity recognition of melanoma antigens. Cohorts of
      three to six patients each received either no interleukin (IL)-2, low-dose IL-2
      (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high
      dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12
      doses). The toxicities associated with this treatment were transient and included
      neutropenia and thrombocytopenia that resolved in all patients. High dose
      intravenous IL-2 was better tolerated by patients after chemotherapy than during
      previous immunotherapy cycles without chemotherapy. No patient exhibited an
      objective clinical response to treatment, although five patients demonstrated
      mixed responses or transient shrinkage of metastatic deposits. This study
      established a nonmyeloablative-conditioning regimen that could be safely
      administered in conjunction with adoptive T-cell transfer and IL-2 in patients
      with metastatic melanoma.

PMID- 12000867
TI  - Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases
      and cultured tumor-infiltrating lymphocytes.
AB  - Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17,
      frequently are observed as targets of tumor infiltrating lymphocytes (TIL)
      originated from HLA-A*0201-expressing patients with melanoma. Furthermore,
      particular clinical relevance was attributed to gp100/pMel17 based on the
      impression that the adoptive transfer of gp100-recognizing TIL was associated
      with clinical responses in a small group of patients. However, the actual
      frequency of specific T cells for these melanoma differentiation antigens has
      never been directly enumerated in ex vivo or in vitro expanded TIL cultures.
      Here, we enumerated melanoma differentiation antigen-specific T-cell precursor
      frequency in TIL using tetrameric HLA/epitope complexes, functionally
      characterizing their responsiveness to cognate epitope by cytokine release assay.
      T-cell precursor frequencies were enumerated in 11 fresh-tumor preparations and
      17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100
      specific T cells could be detected respectively in 5 and 2 of the 11 fresh
      preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one
      exception, melanoma differentiation antigen-specific T-cell precursor frequency
      in fresh material and TIL ranged between 5,000 to 21,000/10(6) CD8+ T cells. T
      cell precursor frequency was not significantly higher in TIL whose administration
      was associated with clinical response. These data provide direct enumeration of
      MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of
      HLA-A*0201.

PMID- 12000868
TI  - Real-time polymerase chain reaction monitoring of epithelial cell adhesion
      molecule-induced T-cell stimulation in patients with lung cancer and healthy
      individuals using LightCycler technology.
AB  - The epithelial cell adhesion molecule is strongly expressed in carcinomas of
      diverse histologic origin and has attracted attention as a target for
      immunotherapy. We have previously demonstrated that the epithelial cell adhesion
      molecule-derived human leukocyte antigen-A*0201-restricted nonamer peptide
      ILYENNVIT(184-192) can be efficiently recognized by peptide-specific cytotoxic T
      lymphocytes (CTL). Using this peptide (Ep-2) we could readily expand precursor
      CTL and demonstrate their cytotoxicity by standard chromium-release assay. We now
      sought to evaluate the immune reactivity of Ep-2-specific CTL expanded from the
      peripheral blood mononuclear cells by real-time quantitative polymerase chain
      reaction assay (LightCycler system) measuring the change in interferon-gamma mRNA
      levels upon stimulation. Cytotoxic T lymphocyte response against the Ep-2 peptide
      in two patients with epithelial cell adhesion molecule-expressing lung cancer and
      three healthy donors was compared with the chromium-release assay. In vitro
      expanded epithelial cell adhesion molecule-specific CTL precursors that exhibited
      significantly elevated interferon-gamma mRNA levels also lysed Ep-2 peptide
      pulsed target cells. Our study indicates that quantitative polymerase chain
      reaction may be a supplement to chromium-release assay for monitoring in vitro
      expanded CTL precursor reactivity.

PMID- 12000869
TI  - Flt-3 ligand and sequential FL/interleukin-2 in patients with metastatic renal
      carcinoma: clinical and biologic activity.
AB  - Flt3 (fms-like tyrosine kinase 3) ligand, a cytokine that stimulates increases in
      the number of dendritic cells (DC) in vivo, has been shown to have antitumor
      activity in murine models via an immune-mediated mechanism. Therefore, we
      examined the clinical activity of this cytokine in patients with an immunologic
      responsive cancer, metastatic renal cell carcinoma. Flt3 ligand (25 microg/kg
      subcutaneous) was administered daily for the first 14 days of a 28-day cycle.
      Although the treatment was well tolerated and was confirmed to induce expansion
      of lineage (Lin)-/HLA-DR+/CD11c+ myeloid DC and Lin-/HLA-DR+/CD123+ plasmacytoid
      DC, no clinical activity was observed. Reasoning that DC expanded by Flt3 ligand
      might potentiate the clinical activity of low-dose interleukin-2, a second study
      was conducted of sequential administration of 25 microg/kg of Flt3 ligand daily
      for 7 days was followed by 11 x 10(6) IU of subcutaneous interleukin-2 for 4
      consecutive days x 4 weeks. In this study, increased numbers of circulating DC
      were again observed, which was followed by increased numbers of activated T
      cells, confirming a biologic effect of each cytokine. However, toxicity and
      clinical efficacy were similar to what has been seen with low-dose interleukin-2
      alone, with two minor responses observed. These results demonstrate that Flt3
      ligand, although capable of inducing expansion of circulating myeloid and
      plasmacytoid DC in patients with metastatic renal cell carcinoma, lacks
      significant clinical activity at the doses and schedules examined.

PMID- 12000870
TI  - Mobilization of dendritic cell precursors in patients with cancer by flt3 ligand
      allows the generation of higher yields of cultured dendritic cells.
AB  - Flt3 ligand (Flt3L) stimulates the proliferation and differentiation of
      hematopoietic cells. Subcutaneous Flt3L administration has been shown to
      effectively manage some murine cancers and in humans, to lead to an increase in
      peripheral blood monocyte and dendritic cell (DC) counts. In the current study,
      we determined the effects of Flt3L therapy on patients with melanoma and renal
      cancer, and in particular, if Flt3L could be used either by enhancing the
      immunization of patients with melanoma to tumor antigen peptides in vivo, or by
      mobilizing DC precursors to allow the production of larger numbers of cultured
      DC. Flt3 ligand administration resulted in a 19-fold increase in DC counts in the
      peripheral blood of patients. The DC generated in vivo appeared only partially
      activated, expressing increased levels of CD86, CD33, and major
      histocompatibility complex class II, but no or low levels of CD80 and CD83. This
      partial activation may account for the lack of enhanced immune responses to
      melanoma antigens and absence of clinical responses in the patients even in
      combination with antigen immunization. Flt3 ligand administration did result,
      however, in a 7-fold increased yield of monocytes per liter of blood from
      leukapheresed patients. Dendritic cells were as readily generated from monocytes
      collected before and after Flt3L therapy, and they stimulated allogeneic T-cell
      proliferation in a mixed leukocyte reaction to a similar magnitude. Thus, the use
      of Flt3L may be an important method to mobilize DC precursors to allow patient
      therapy with larger numbers of cultured DC.

PMID- 12000871
TI  - The new culture of flat heads: a global phenomenon or a local variance.

PMID- 12000872
TI  - Coronal suturectomy does not cause acute postoperative displacement in the
      cranial bases of craniosynostotic rabbits.
AB  - Approximately 300 to 500 infants per 1,000,000 have prematurely fused cranial
      sutures (craniosynostosis). Craniosynostosis can result in increased intracranial
      pressure and craniofacial deformities, which often require extensive and costly
      craniofacial surgery. Because the neurocranium and basicranium are
      developmentally interrelated, understanding their influence on one another is
      important for surgical planning. Although surgery has been found to have long
      term effects on the cranial bases of craniosynostotic human beings and rabbits,
      the biological mechanisms behind these effects remain uncertain. Some researchers
      have suggested that the surgical release of synostosed sutures alters long-term
      growth patterns, resulting in cranial base differences between craniosynostotic
      individuals who undergo surgery and those who do not. Additionally, some
      investigators have proposed that an acute and surgically related displacement of
      basicranial elements may contribute to the observed differences. The current
      study examines acute postoperative changes in four lengths, three angles, and
      three triangles between cranial base landmarks in a sample of seven New Zealand
      white rabbits with familial nonsyndromic craniosynostosis. Results indicate that
      suturectomy caused no statistically significant (P < 0.05) acute length, angular,
      or shape differences in the cranial base. Thus, previous long-term cranial base
      differences found between rabbits that were operated on and those that were not
      were probably not caused by an acute displacement of skeletal elements as a
      result of surgery. These findings suggest that postoperative cranial base changes
      may be related more to chronically altered growth patterns than to acutely
      altered changes in intracranial pressure or dural tension.

PMID- 12000873
TI  - Identity of "orbitozygomatic muscle".
AB  - Our exploration disclosed 17 (40%) stranded muscles of 42 hemifacial specimens of
      Korean cadavers. We name this distinct muscle "Orbitozygomatic Muscle (OZM)" that
      is either an aberrant orbicularis oculi muscle or a separate muscle. A triangular
      space bounded superiorly by the lowest edge of the orbicularis oculi muscle
      (OOM), laterally by Zygomaticus Minor, and inferiorly by OMZ gives way to
      neurovascular bundle and suborbicularis oculi fat pad (SOOF).

PMID- 12000874
TI  - Molding of the regenerate in mandibular distraction: Part 1: Laboratory study.
AB  - Distraction osteogenesis has evolved as a mainstream surgical technique for
      lengthening and augmentation of the hypoplastic mandible. As clinical experience
      accumulated, there developed the need to "mold" the bony regenerate to avoid the
      development of postdistraction malocclusion and to achieve the desired
      craniofacial form. Although the potential to mold the regenerate has important
      clinical implications, the safety and efficacy of such an acute manipulation of
      the bony regenerate form have not yet been investigated in the laboratory. The
      purpose of this study was to determine if the distraction regenerate could be
      molded and result in a bony union. Four adult female dogs underwent bilateral
      mandibular distraction with an external multiplanar device (Stryker, Osteonics).
      After a latency period of 5 days, the mandibles underwent linear
      (anteroposterior) and angular (superoinferior) distraction to produce an anterior
      open bite of approximately 30 degrees. At the conclusion of the distraction
      procedure, the distraction sites were molded to close the open bite. In two dogs,
      the maneuver was performed over 3 days by changing the angulation of the devices
      (gradual molding), and in the other two dogs, molding was achieved with a single
      movement (acute molding). In the latter, the distraction devices were adjusted
      and reapplied to allow for anatomical fixation during the consolidation period of
      49 days. According to the research protocol, the mandibles were assessed serially
      by cephalograms and computed tomography (CT) scans. All dogs survived the study
      without complications. The bony regenerate was easily molded in both groups to
      close the surgically created open bite. After molding, all the regenerates showed
      CT scan evidence of solid bone (consolidation), which was classified as
      "extended" on the Hamanishi scale. After the dogs were killed and soft tissue was
      removed, the regenerate seemed to be robust on gross examination without any
      evidence of fibrous nonunion. In addition, histological study of the regenerate
      confirmed the bony union. The study demonstrates that the mandible can be
      successfully molded into a desired anatomical position immediately after
      distraction without producing a fibrous union. Furthermore, it has been
      demonstrated that the bony regenerate is sufficiently malleable before
      consolidation to undergo either acute or gradual angular molding without
      disturbing osteogenic potential. The ability to mold the regenerate without the
      fear of creating a fibrous union or destroying bony potential provides the
      surgeon the capability to optimize the dental occlusion and mandibular form as
      part of the distraction treatment process.

PMID- 12000875
TI  - Holding power of bioabsorbable ciprofloxacin-containing self-reinforced poly-L/DL
      lactide 70/30 bioactive glass 13 miniscrews in human cadaver bone.
AB  - Antibiotics-plus bioactive glass-containing bioabsorbable self-reinforced (SR)
      polylactide screws have been developed for antibacterial osteoconductive bone
      fixation. The aim of the present study was to test the pullout properties of
      these recently developed miniscrews. Ciprofloxacin-plus bioactive glass
      containing SR-polylactide miniscrews (BC) were compared with miniscrews made of
      neat SR-polylactide (A), SR-polylactide with bioactive glass (B), and
      ciprofloxacin-containing SR-polylactide (C). BC miniscrews and their controls (A,
      B, C) (all of length 6.0 mm, core diameter 1.45 mm, thread diameter 2.0 mm) were
      applied to one pair of cadaveric fibulae. Pullout force was measured using a
      materials testing machine. We carried out 49-50 pullout tests for each implant
      type. The Mann-Whitney test and Student's t-test were used for statistical
      evaluation. The pullout force for BC miniscrews was 114.9 +/- 34.0 (SD) N.
      Pullout forces for control miniscrews were 162.7 +/- 37.8 N (A), 99.1 +/- 16.2 N
      (B), and 142.9 +/- 26.9 N (C). Differences between the four groups were
      statistically significant (p < 0.001). Ciprofloxacin-plus bioactive glass
      containing polylactide miniscrews have good holding power to human cadaver
      fibulae. However, adding bioactive glass and ciprofloxacin components to neat SR
      polylactide results in lower pullout values.

PMID- 12000878
TI  - Experimental mandibular regeneration by distraction osteogenesis with submerged
      devices: preliminary results of a canine model.
AB  - The authors describe a new technique for reconstruction of mandibular body
      defects. The feasibility of distraction osteogenesis with submerged (internal)
      devices for reconstruction of segmental mandibular defects is investigated in an
      experiment with five adult dogs. A segmental mandibulectomy was performed on the
      horizontal ramus. The bony defect was regenerated using distraction osteogenesis
      (bone transport) at a rate of 1 mm daily. The animals were killed after the
      consolidation period. Complete bone regeneration of the surgically created gap
      was successful in three of five dogs. Two animals failed to create new bone. In
      these two cases, the screws did not offer proper stability to the bony fragments,
      and this caused a lack of ossification. This experimental study demonstrates the
      possibility to use internal distraction devices to reconstruct segmental
      mandibular defects in a canine model. Internal devices show enormous advantages
      in comparison with the external ones. This method with no donor-site morbidity
      may become a very useful option in human mandibular reconstruction.

PMID- 12000879
TI  - Tissue-engineered bone using mesenchymal stem cells and a biodegradable scaffold.
AB  - Bone marrow has been shown to contain a population of rare cells capable of
      differentiating to the cells that form various tissues. These cells, referred to
      as mesenchymal stem cells (MSCs), are capable of forming bone when implanted
      ectopically in an appropriate scaffold. The aim of this study was to investigate
      the potential of a new beta-tricalcium phosphate (beta-TCP) as a scaffold and to
      compare the osteogenic potential between beta-TCP and hydroxyapatite (HA). The
      beta-TCP and HA loaded with MSCs were implanted in subcutaneous sites and
      harvested at 1, 2, 4, and 8 weeks after implantation for biochemical and
      histological analysis. Biochemically, in both beta-TCP and HA composites, the
      alkaline phosphatase activity in the composites could be detected and was
      maintained at a high level for 8 weeks. In the histological analysis, active bone
      formation could be found in both the beta-TCP and HA composites. These findings
      suggest that beta-TCP could play a role as a scaffold as well as HA. The
      fabricated synthetic bone using biodegradable beta-TCP as a scaffold in vivo is
      useful for reconstructing bone, because the scaffold material is absorbed several
      months after implantation.

PMID- 12000881
TI  - Mandibular form in a rabbit model of familial nonsyndromic coronal suture
      synostosis.
AB  - Nonsyndromic coronal suture synostosis produces predictable and well-documented
      morphologies of the cranial vault with anteroposterior growth restrictions and
      mediolateral compensatory growth. The potential effects of nonsyndromic coronal
      suture synostosis on mandibular form are not as clear, however. This study was
      designed to evaluate whether coronal suture synostosis is associated with
      alterations in mandibular form by using a familial rabbit model of coronal suture
      synostosis. To assess this potential relation, the following hypothesis was
      tested: mandibular form in rabbits with coronal suture synostosis is
      significantly (P < 0.05) different from that seen in normal rabbits. The cleaned
      and dried mandibles of 33 adult New Zealand white rabbits were used (12 from
      normal rabbits, 13 from rabbits with delayed-onset synostosis, and 8 from rabbits
      with complete coronal suture synostosis). Seven anatomical landmarks on the
      mandible were located and digitized in three dimensions: anterior molar on the
      alveolus, posterior molar on the alveolus, coronoid process, anterior pole of the
      condyle, condylar process, angular process, and mandibular angle. To describe the
      mandibular condyle, the distance from the anterior pole to the posterior pole of
      the condyle was measured with digital sliding calipers, as was the distance
      between the medial and lateral poles. A shape ratio was then created using the
      dividend of these sums. Statistical analyses of mean form differences between
      mandibles were executed using Euclidean distance matrix analysis. Statistical
      analyses of the mandibular condyle linear and shape measurements were analyzed
      using one-way ANOVA in the three groups. Results showed that complete coronal
      suture synostosis is associated with significant (P < 0.05) differences in
      mandibular form compared with that of normal rabbits but that mandibular form in
      rabbits with delayed-onset synostosis does not differ from that of normal rabbits
      (P > 0.05). In particular, distances involving the coronoid process in rabbits
      with coronal suture synostosis were significantly different, paralleling previous
      work in human patients with coronal synostosis. There are no intrinsic condylar
      linear or shape differences between any of these groups, however. The form
      difference noted is most likely secondary to the synostosed coronal suture and
      may reflect alterations in the cranial base or masticatory musculature in this
      rabbit model.

PMID- 12000882
TI  - Early revascularization of membranous inlay bone graft in canine mandible model.
AB  - The early revascularization of a membranous inlay bone graft in a canine mandible
      was investigated using bone scans and histological examinations. Eight 5-month
      old mongrel dogs were used as the subjects. The inlay bone graft, a 1- x 2-cm
      critically sized bone, was completely separated from the lower border of the
      canine mandible and then refixed to the original site. Bone scans and
      histological examinations were performed in the first, second, third, and fourth
      postoperative weeks. The bone scan in the first postoperative week revealed
      radioisotope uptake on the margin of the grafted bone with an isotope count that
      was 21% of the normal bone uptake. In the second postoperative week, the
      radioisotope uptake in the grafted bone increased to 52% of the normal bone
      uptake. In the third and fourth postoperative weeks, the isotope uptakes were
      111% and 124%, respectively. The histological findings in the first postoperative
      week showed an absence of osteoblastic activity and 6 viable blood vessels in a
      field magnified x 200, which was the equivalent of 25% of the vessels of the
      normal bone. In the second postoperative week, osteoblastic activity was noted,
      and the number of viable blood vessels increased to 15, that is, 63% of the
      vessels of the normal bone. In the third postoperative week, there was an
      increase in osteoblastic activity, and the number of viable blood vessels was 21,
      that is, 88% of the vessels of the normal bone. In the fourth postoperative week,
      there was a marked increase in osteoblastic activity with the number of vessels
      reaching 23, that is, 96% of the normal bone. In summary, revascularization of
      the membranous inlay bone graft began within the first week after the bone graft
      and thereafter gradually increased. In the third postoperative week,
      revascularization returned to a near-normal value compared with the value of the
      adjacent normal mandibular bone.

PMID- 12000883
TI  - Bony orbital distances among the Filipino population.
AB  - Six hundred and seventy seven radiographs were selected from the logs of films
      taken in a major hospital in Metro Manila, Philippines over the course of the
      previous year. Two hundred and eighty-eight female and 389 male, healthy
      Filipinos between the ages of birth and twenty years were selected based on the
      availability of a modified Waters' projection and lateral skull film taken at the
      same time. Measurements for the lateral orbital wall were made at the site of the
      suture on the medial surface of the zygomatic bone. The medial orbital wall
      measurement was the distance between the dacrya using a correction factor formula
      of CF = D-d/D where D is the target film distance and d is the object film
      distance (1). The actual bony measurements were calculated. The data was gathered
      and plotted according to sex and in age in years. Graphs were generated using SAS
      over a graph software. Lines were smooth using cubic spline technique developed
      by Reinsch with the smoothest value of 75 (2). The mean plus two, four, and six
      standard deviations were included in each of the curves.

PMID- 12000884
TI  - LeFort III internal distraction in syndromic craniosynostosis.
AB  - Distraction osteogenesis of the mid-face alleviates the requirements of
      substantial autogenous bone grafts and donor site morbidity and alleviates the
      restriction of the soft-tissue envelope in gaining advancement of the mid-face. A
      prospective study, over a 14-month period, was initiated to evaluate the results
      of seven consecutive patients undergoing mid-facial advancement who were treated
      with Le Fort III internal distraction using the MID device. All patients had
      syndromic craniosynostoses and six patients had previously undergone fronto
      orbital advancement. Four patients had symptoms of airway obstruction and one
      patient was tracheostomy dependent. Six of the patients completed the distraction
      as planned. Lateral cephalograms were analyzed and the mean linear distraction
      was 18 mm with a range of 8 mm to 23 mm. Complications included infection (one
      patient), mechanical failure (one patient), intraoperative fragment dysjunction
      (three patients), velopharyngeal insufficiency (one patient), conjunctivitis (two
      patients), trismus (six patients), and bony irregularities. It was concluded that
      in our Unit's future protocol for managing infant syndromic synostoses,
      synostectomies and cranial vault remodeling will be undertaken in infants as
      before, but that in early childhood, patients with severe mid-facial hypoplasia
      and/or respiratory compromise will be offered distraction osteogenesis as a
      substitute for the traditional Le Fort III advancement and bone grafting.

PMID- 12000885
TI  - Segmental distraction of the midface in a patient with Crouzon syndrome.
AB  - We treated midface hypoplasia in a 20-year-old woman with Crouzon syndrome using
      a rigid external distraction device. The patient showed severe exophthalmos and
      maxillary retrusion, although relatively good occlusion had been achieved by long
      term orthodontic procedures. We considered that our patient's particular
      condition could not be resolved by the usual Le Fort III osteotomy/midface
      distraction procedure, so we devised a segmental approach. The midface, mobilized
      by Le Fort III osteotomy, was divided into two segments by Le Fort I osteotomy;
      each fragment was connected to the rigid external distraction device to be
      distracted separately. Distraction was begun after 1 day at 1 mm/day. The upper
      and lower segments were distracted over 17 and 12 days, respectively. The
      patient's occlusion was fully corrected, and her facial contour was significantly
      improved. After 3 weeks of consolidation, we removed the distraction device. The
      clinical course was without complication, and no relapse was observed on the
      cephalogram or computed tomography scan obtained 1 year after the procedure. Our
      modified technique was helpful in increasing the usefulness of the external
      distraction system and in refining the midface distraction procedure.

PMID- 12000886
TI  - Distraction osteogenesis of zygomatic bone grafts in a patient with Treacher
      Collins syndrome: a case report.
AB  - Zygomatic aplasia in patients with Treacher Collins syndrome requires
      reconstruction with autogenous bone grafts. Serial bone grafting may be required
      if optimal malar projection is not achieved with the initial procedure. This
      report demonstrates the use of distraction osteogenesis in repositioning a
      previously bone-grafted zygoma in an adolescent patient with Treacher Collins
      syndrome, thus avoiding the need for repeat bone graft harvest. The limitations
      of this technique include difficulty in achieving the desired vector of
      distraction and the potential of graft devitalization. Nevertheless, the case
      report illustrates the versatility of distraction osteogenesis in skeletal
      augmentation/remodeling.

PMID- 12000888
TI  - Preshaped hydroxyapatite tricalcium-phosphate implant using three-dimensional
      computed tomography in the reconstruction of bone deformities of
      craniomaxillofacial region.
AB  - We prepared solid life-sized models and templates of implants based on three
      dimensional computed tomography data in six cases with a bone deformity of the
      craniomaxillofacial region. After simulation surgery using these models and
      templates, the preshaped hydroxyapatite-tricalcium phosphate (HAP-TCP) implants
      were prepared to fill in the facial bone defects, and implantation was performed.
      Consequently, implants fitted the individual bone defects, and satisfactory
      facial contouring was obtained in five cases. In one case with severe cutaneous
      scarring in the grafted site, it was necessary to reduce the volume of the
      preshaped HAP-TCP implant during surgery. In conclusion, the three-dimensional,
      solid, life-sized model and template are useful for preoperative detailed
      simulation, and the use of preshaped HAP-TCP implants based on the template
      probably contributes to successful reconstruction of complex facial bone
      deformities and to the reduction of surgical invasion, resulting in achievement
      of better results.

PMID- 12000889
TI  - Proximal segment displacement in mandibular distraction osteogenesis.
AB  - Distraction osteogenesis has been advocated for treatment of the mandibular
      deformity in patients with hemifacial microsomia (HFM). During the active phase,
      the force of distraction pushes the distal segment of the mandible down, creating
      a distraction gap. Because of the abnormal temporomandibular joint anatomy in HFM
      patients, the proximal segment may not seat in the glenoid fossa and thus may be
      displaced with distraction. The purpose of this study was to determine the
      vector(s) of proximal segment movement during mandibular distraction using a
      semiburied device. Two investigators traced the immediate pre-and postdistraction
      panoramic radiographs of 12 HFM patients (mean age at operation = 8.4 years, mean
      distraction = 28 mm) who had mandibular distraction with a semiburied device.
      Radiographic analysis, based on a vertical maxillary reference line, measured
      change in condylar position with angular and linear measurements. Inter-rater
      reliability for the tracing and analysis was shown with a correlation coefficient
      between 0.89 and 0.99 for all measures. Based on the angular and linear
      measurements, 10 of the 12 patients had superior movement of the proximal segment
      with distraction. Sagittal movement of the proximal segment could not be judged
      adequately. This study was based on measurements made on panoramic radiographs.
      Direct measurements could not be made; thus, it was not possible to estimate
      proximal segment movement in millimeters or as a percentage of total movement.
      Further studies to document proximal segment movement using computed tomography
      scans may provide more quantitative data.

PMID- 12000891
TI  - Le Fort III distraction osteogenesis of midface-retrusion in a case of Hajdu
      Cheny syndrome.
AB  - Le Fort III maxillary distraction osteogenesis using the RED system and
      advancement genioplasty was successfully performed for the midfacial retrusion
      and to eliminate severe snoring during sleep in a rare case of Hajdu Cheny
      syndrome. This syndrome is characterized by slowly progressive systemic osseous
      dysplasia, exhibiting craniofacial disfigurements and other skeletal deformity,
      but no description is found in a plastic surgical treatment up to now. A rare
      entity of this syndrome is also presented.

PMID- 12000892
TI  - Penetrating craniofacial injury in a pediatric patient.
AB  - Penetrating craniofacial injuries are rare especially in the pediatric age group.
      They are potentially life-threatening and challenging injuries. We describe an
      unusual trauma in a 30-month-old child who suffered a craniofacial injury caused
      by TV antenna. Clinical examination and radiological investigation showed the
      antenna penetrating the hard palate, left posterior nasal choana, sphenoid sinus,
      and skull base, up to pituitary fossa. There was no evidence of great vessels
      injury that confirmed by cerebral angiography. Transpalatal approach was used to
      remove the antenna and repair the skull base defect. There was no neurological or
      visual activity deficit postoperatively. The child developed diabetes insipidus
      that is well controlled using desmopressin.

PMID- 12000893
TI  - Sublingual epidermoid cyst.
AB  - Dermoid and epidermoid cysts are developmental pathologies that occur in the head
      and neck with an incidence ranging from 1.6 to 6.9%, and they represent less than
      0.01% of all oral cavity cysts. Our purpose is to report a case of sublingual
      epidermoid cyst of the floor of the mouth. We studied and operated on an 18-year
      old white male patient showing a large swelling of oral floor. His main symptoms
      were difficulty breathing, swallowing, and speaking. At his birth the patient's
      tongue was adherent to the floor of the mouth. His father had the same problem at
      birth. Both father and son underwent surgical separation of tongue, during the
      post-neonatal period. After the surgical removal of the swelling, under general
      anesthesia, all the patient's symptoms were missed. Histological examination of
      the mass confirmed the diagnosis of an epidermoid cyst. No relapse of the lesion
      was present in ten months of follow-up. Many theories are proposed on the
      etiology of the epidermoid and dermoid cyst. In this case a traumatic event can
      be found, such as an operation of the tongue in neonatal age. However a
      multifactorial origin must be assumed for justifying the fact that the patient's
      father did not develop a dermoid cyst although he had the same problem of an
      adherent tongue and was operated on.

PMID- 12000894
TI  - Familial external angular dermoid: evidence for a genetic link?
AB  - Congenital craniofacial dermoid cysts are hamartomas of ectodermal and mesodermal
      origin, made up of keratinizing epithelium lining a cavity containing dermal skin
      appendages. They usually present as an asymptomatic, firm, round mass, usually
      noticed at birth or in the first year. They are thought to occur as a result of
      ectodermal sequestration at lines of fusion during embryological development.
      Although nasal and epibulbar dermoid cysts have occurred in families and have
      been associated with inheritable gene defects, there has previously been no
      evidence for a similar etiology in external angular cases. We present the first
      description of external angular dermoids occurring in siblings suggesting that
      this subgroup may, in some instances, also have a genetic origin.

PMID- 12000896
TI  - Inferior alveolar nerve impairment after mandibular sagittal split osteotomy: an
      analysis of spontaneous recovery patterns observed in 60 patients.
AB  - Sensory impairment after bilateral sagittal split osteotomy (BSSO) due to
      inferior alveolar nerve (IAN) lesions may be either temporary or permanent and
      either complete or partial. The aim of this prospective study is to evaluate, by
      means of objective sensory testing, IAN sensory disturbances development in
      patients who underwent BSSO.IAN sensory disturbances development at the first
      week, fourth week, sixth month, and twelfth month of follow-up review in a group
      of 60 patients who underwent BSSO from January 1, 1998, to July 31, 1999, at the
      Maxillofacial Surgery Department of the "La Sapienza" University of Rome. The 60
      patients were examined in the presurgical period; the IAN functionality regarding
      thermal sensibility, nociception, and two-point discrimination, was assessed at
      follow-up in 120 sides. In our study the highest rate of spontaneous recovery of
      the entire IAN functionality was observed at the sixth month. This finding
      witnesses how neuropraxia and axonotmesis give a spontaneous recovery that most
      frequently occurs within 6 months from surgery, independently from age and sex of
      the patient. The persistence of anesthesia over 12 months could be a sign of
      neurotmesis.

PMID- 12000897
TI  - Oral-facial-digital syndrome type II (Mohr syndrome): clinical and genetic
      manifestations.
AB  - The oral-facial-digital syndromes (OFDS) represent a heterogenous group of
      disorders characterized by oral malformation, facial anomalies, and digital
      anomalies. Type II OFDS was reported by Mohr in 1941. Mohr syndrome is an
      autosomal recessive inherited disease characterized by median cleft lip, poly
      lobed tongue, absence of medial incisors, and polydactyly of hands and feet. Some
      other different expressive types of OFDS cases have been reported, and identified
      with 11 different clinical entities up to the present. Until now, only three
      cases of OFDS II in Japanese patients have been detected except for our patient.
      At this time, we observed a Japanese patient of Mohr syndrome with median cleft
      lip and tongue, hypertrophied frenula, absence of left medial incisor, and
      bilateral bifidity of great toe. Lip and tongue plasty was performed at 7 months
      after birth and toe plasty was done at 11 months with good results.

PMID- 12000898
TI  - Chronic headache as a sequela of rigid fixation for craniosynostosis.
AB  - Rigid fixation has been used over the past 20 years for the long-lasting
      correction of traumatic and congenital craniofacial defects. It has been noted
      that the use of plates and screws can result in the migration of the hardware
      through the skull to the inner cerebral cortex where it embeds in the dura. In
      addition, there is controversy concerning the safety of using titanium plates in
      the pediatric population. We report here on an 8-year-old boy who presented to
      our clinic with a chronic headache after rigid craniofacial fixation using
      titanium plates 7 years before.

PMID- 12000899
TI  - A new technique for cranial bone osteofixation: use of bioabsorbable tacks and
      plates to fix parietal bone split grafts used for reconstruction of a
      posttraumatic frontal bone defect.
AB  - Recent advances in bioabsorbable devices have introduced tacks that do not
      require tapping. This may help to reduce operative time and, consequently, costs.
      The goal of this study was to demonstrate the feasibility of a new method of
      cranial bone osteofixation using novel bioabsorbable tacks and plates instead of
      screws. A 36-year-old man presented for elective cranioplasty to reconstruct a
      large frontal cranial bone defect that followed a decompression operation
      performed because of a head injury sustained 6 months previously. Cranioplasty
      was performed using split parietal bone grafts to reconstruct the defect. Bone
      grafts were fixed together and to the skull using self-reinforced (SR)
      poly(L/DL)lactide [SR-poly(L/DL)lactide] (70/30) (Biosorb FX) plates (n = 10) and
      tacks (n = 98). The plates were 0.6 mm thick, 102 mm long, and 12 mm wide. The
      tacks had a maximum thread diameter of 2 mm and a length of 6 mm. The tacks used
      did not require any tapping procedure, and they were applied using a special
      applicator gun. Stable and secure fixation was obtained during surgery. The
      postoperative period was uneventful, except for delayed epithelialization of a
      small area (1 x 0.5 cm) over the frontal skin that healed later. One year after
      surgery, the cosmetic result was excellent, and no complications were detected.
      Stabilization of large cranial bone pieces can be achieved using bioabsorbable SR
      poly(L/DL)lactide plates and tacks, with excellent cosmetic results. The method
      is thought to be reliable and may help to reduce operative time.

PMID- 12000900
TI  - A new regenerative approach to oromandibular reconstruction after the resection
      of head and neck malignant tumor.
AB  - We developed a new regenerative oromandibular reconstruction technique. In our
      technique, bone marrow was removed from surgically resected mandible, and then
      the mandible was heat-treated and prepared into a cortical bone tray. This tray
      was fixed on the defect area, iliac cancellous bone was grafted into its lumen,
      the entire circumference was covered with the muscle part of pectoral major
      myocutaneous flap, and the oral defect and the skin defect on the lower jaw were
      reconstructed with the skin paddles of the skin island of the flap. Two patients
      were treated with this technique after the removal of oral cavity cancer. The
      patients did not develop postoperative complications, the reconstructed mandible
      as well as the flap were completely taken, and normal shape of the mandible was
      regained. This technique would be one of the useful oromandibular reconstruction
      methods.

PMID- 12000903
TI  - Laryngotracheal anomalies in children with craniofacial syndromes.

PMID- 12000904
TI  - Firearm safety: where we are, where we need to be.

PMID- 12000905
TI  - Ebola fever: the African emergency.
AB  - The Ebola virus produces one of Africa's most lethal viral hemorrhagic fever
      (VHF) infections. Statistically, Ebola fever is at the bottom of Africa's list of
      infectious diseases, but the speed with which it induces agonizing death puts
      Ebola fever at the top of Africa's emergencies. Many aspects of the virus are
      unknown and have eluded medical scientists for 3 decades. Hence enormous
      difficulties may be encountered in treating, preventing, and controlling Ebola
      fever. In this article, the origin of the disease is traced, followed by a
      description of the Ebola fever triad, with some insights into the perspectives
      that may complicate treatment and control of the disease. The clinical
      manifestations are described in relation to the progression of the disease.
      Patients with the Ebola virus are admitted to the hospital as an emergency with
      the activation of a disaster-type plan of action.

PMID- 12000906
TI  - The secrets of gun violence in America: what we don't know is killing us.

PMID- 12000907
TI  - Basic emergency lifesaving skills (BELS): a framework for teaching skills to
      children and adolescents.

PMID- 12000908
TI  - Transporting patients with lethal contagious infections.

PMID- 12000909
TI  - Cops & docs: a gun violence injury prevention program.

PMID- 12000910
TI  - MedSun: user facility reporting for the new millennium.

PMID- 12000913
TI  - Emergency nurse's response to terrorism.

PMID- 12000914
TI  - Identification of iron sulphide grains in protoplanetary disks.
AB  - Sulphur is depleted in cold dense molecular clouds with embedded young stellar
      objects, indicating that most of it probably resides in solid grains. Iron
      sulphide grains are the main sulphur species in cometary dust particles, but
      there has been no direct evidence for FeS in astronomical sources, which poses a
      considerable problem, because sulphur is a cosmically abundant element. Here we
      report laboratory infrared spectra of FeS grains from primitive meteorites, as
      well as from pyrrhotite ([Fe, Ni](1-x)S) grains in interplanetary dust, which
      show a broad FeS feature centred at approximately 23.5 micrometres. A similar
      broad feature is seen in the infrared spectra of young stellar objects, implying
      that FeS grains are an important but previously unrecognized component of
      circumstellar dust. The feature had previously been attributed to FeO. The
      observed astronomical line strengths are generally consistent with the depletion
      of sulphur from the gas phase, and with the average Galactic sulphur/silicon
      abundance ratio. We conclude that the missing sulphur has been found.

PMID- 12000917
TI  - Peer review reviewed.

PMID- 12000918
TI  - US should back research cloning.

PMID- 12000920
TI  - Academy protests as agriculture agency abandons visa renewals.

PMID- 12000923
TI  - Draft mouse genome makes public debut.

PMID- 12000925
TI  - NIH ponders issues of scale in protein push.

PMID- 12000927
TI  - Spying charges dropped as Japanese biologist cuts deal.

PMID- 12000928
TI  - Neurologists strike gold in drug screen effort.

PMID- 12000931
TI  - Ecosystem health: the state of the planet.

PMID- 12000932
TI  - Neuroscience: magnetic mind games.

PMID- 12000933
TI  - Basic or applied, it's the interaction that counts.

PMID- 12000934
TI  - Fundamentals are still relevant in toxicology.

PMID- 12000939
TI  - Astrophysical spouts: the jet set.

PMID- 12000935
TI  - Creating a bioinformatics nation.

PMID- 12000940
TI  - Biogeochemistry: a lowdown on oxygen.

PMID- 12000941
TI  - Cytoskeleton: microtubules do the twist.

PMID- 12000942
TI  - Geology: a foot in the past.

PMID- 12000943
TI  - Physiology: the pitfalls of power laws.

PMID- 12000945
TI  - Applied physics: bridge for the terahertz gap.

PMID- 12000946
TI  - Palaeoecology: climate records spruced up.

PMID- 12000947
TI  - Cell biology: keeping the genome in shape.

PMID- 12000949
TI  - Microbiology: eukaryotic diversity in Spain's River of Fire.
AB  - The Rio Tinto, known by the Phoenicians as 'Ur-yero', or 'River of Fire', because
      of its deep red colour and high acidity, flows through the world's largest
      pyritic belt in southwestern Spain. Surprisingly, eukaryotic microbes are the
      principal contributors of biomass in this hostile river, which has a pH of 2 and
      contains much higher concentrations of heavy metals than are typically found in
      fresh waters. Here we show that the Rio Tinto shows an unexpected degree of
      eukaryotic diversity and includes new lineages that we have identified by
      sequence analysis of genes encoding small-subunit ribosomal RNAs. The diversity
      of these eukaryotes is much greater than that of prokaryotes, whose metabolism is
      responsible for the extreme environment.

PMID- 12000950
TI  - Brain damage: neglect disrupts the mental number line.
AB  - A popular metaphor for the representation of numbers in the brain is the 'mental
      number line', in which numbers are represented in a continuous, quantity-based
      analogical format. Here we show that patients with hemispatial neglect misplace
      the midpoint of a numerical interval when asked to bisect it (for example,
      stating that five is halfway between two and six), with an error pattern that
      closely resembles the bisection of physical lines. This new form of
      representational neglect constitutes strong evidence that the mental number line
      is more than simply a metaphor, and that its spatial nature renders it
      functionally isomorphic to physical lines.

PMID- 12000951
TI  - Electrochemistry: building on bubbles in metal electrodeposition.
AB  - In the electrodeposition of metals, a widely used industrial technique, bubbles
      of gas generated near the cathode can adversely affect the quality of the metal
      coating. Here we use phase-contrast radiology with synchrotron radiation to
      witness directly and in real time the accumulation of zinc on hydrogen bubbles.
      This process explains the origin of the bubble-shaped defects that are common in
      electrodeposited coatings.

PMID- 12000952
TI  - HIV in Africa (Communication arising): chemokine-receptor genes and AIDS risk.
AB  - Schliekelman et al. have provided a model to quantify the speed at which HIV
      resistance haplotypes can become enriched in a susceptible population through a
      delay in the onset of AIDS, permitting greater lifetime reproduction and the
      selection of AIDS-delaying haplotypes. But we question their conclusion that
      there could be a rapid evolution of resistance to AIDS onset in some African
      populations if the current HIV epidemic persists, as this depends on an untested
      assumption: that variant forms of the chemokine-receptor-5 (CCR5) gene impart
      selective advantages or disadvantages in Africa that are comparable to those
      reported for African Americans. Here we test this premise in a large Ugandan
      population, and find that CCR5 variants are not associated with HIV/AIDS disease
      risk in Africa--the origin and centre of the current AIDS pandemic. This gene may
      therefore not be subject to rapid evolutionary change as a result of the HIV
      epidemic in Africa.

PMID- 12000954
TI  - Spin-galvanic effect.
AB  - There is much recent interest in exploiting the spin of conduction electrons in
      semiconductor heterostructures together with their charge to realize new device
      concepts. Electrical currents are usually generated by electric or magnetic
      fields, or by gradients of, for example, carrier concentration or temperature.
      The electron spin in a spin-polarized electron gas can, in principle, also drive
      an electrical current, even at room temperature, if some general symmetry
      requirements are met. Here we demonstrate such a 'spin-galvanic' effect in
      semiconductor heterostructures, induced by a non-equilibrium, but uniform
      population of electron spins. The microscopic origin for this effect is that the
      two electronic sub-bands for spin-up and spin-down electrons are shifted in
      momentum space and, although the electron distribution in each sub-band is
      symmetric, there is an inherent asymmetry in the spin-flip scattering events
      between the two sub-bands. The resulting current flow has been detected by
      applying a magnetic field to rotate an optically oriented non-equilibrium spin
      polarization in the direction of the sample plane. In contrast to previous
      experiments, where spin-polarized currents were driven by electric fields in
      semiconductor, we have here the complementary situation where electron spins
      drive a current without the need of an external electric field.

PMID- 12000953
TI  - Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).
AB  - Streptomyces coelicolor is a representative of the group of soil-dwelling,
      filamentous bacteria responsible for producing most natural antibiotics used in
      human and veterinary medicine. Here we report the 8,667,507 base pair linear
      chromosome of this organism, containing the largest number of genes so far
      discovered in a bacterium. The 7,825 predicted genes include more than 20
      clusters coding for known or predicted secondary metabolites. The genome contains
      an unprecedented proportion of regulatory genes, predominantly those likely to be
      involved in responses to external stimuli and stresses, and many duplicated gene
      sets that may represent 'tissue-specific' isoforms operating in different phases
      of colonial development, a unique situation for a bacterium. An ancient synteny
      was revealed between the central 'core' of the chromosome and the whole
      chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium
      diphtheriae. The genome sequence will greatly increase our understanding of
      microbial life in the soil as well as aiding the generation of new drug
      candidates by genetic engineering.

PMID- 12000955
TI  - Terahertz semiconductor-heterostructure laser.
AB  - Semiconductor devices have become indispensable for generating electromagnetic
      radiation in everyday applications. Visible and infrared diode lasers are at the
      core of information technology, and at the other end of the spectrum, microwave
      and radio-frequency emitters enable wireless communications. But the terahertz
      region (1-10 THz; 1 THz = 10(12) Hz) between these ranges has remained largely
      underdeveloped, despite the identification of various possible applications--for
      example, chemical detection, astronomy and medical imaging. Progress in this area
      has been hampered by the lack of compact, low-consumption, solid-state terahertz
      sources. Here we report a monolithic terahertz injection laser that is based on
      interminiband transitions in the conduction band of a semiconductor (GaAs/AlGaAs)
      heterostructure. The prototype demonstrated emits a single mode at 4.4 THz, and
      already shows high output powers of more than 2 mW with low threshold current
      densities of about a few hundred A cm(-2) up to 50 K. These results are very
      promising for extending the present laser concept to continuous-wave and high
      temperature operation, which would lead to implementation in practical photonic
      systems.

PMID- 12000956
TI  - Ocean productivity before about 1.9 Gyr ago limited by phosphorus adsorption onto
      iron oxides.
AB  - After the evolution of oxygen-producing cyanobacteria at some time before 2.7
      billion years ago, oxygen production on Earth is thought to have depended on the
      availability of nutrients in the oceans, such as phosphorus (in the form of
      orthophosphate). In the modern oceans, a significant removal pathway for
      phosphorus occurs by way of its adsorption onto iron oxide deposits. Such
      deposits were thought to be more abundant in the past when, under low sulphate
      conditions, the formation of large amounts of iron oxides resulted in the
      deposition of banded iron formations. Under these circumstances, phosphorus
      removal by iron oxide adsorption could have been enhanced. Here we analyse the
      phosphorus and iron content of banded iron formations to show that ocean
      orthophosphate concentrations from 3.2 to 1.9 billion years ago (during the
      Archaean and early Proterozoic eras) were probably only approximately 10-25% of
      present-day concentrations. We suggest therefore that low phosphorus availability
      should have significantly reduced rates of photosynthesis and carbon burial,
      thereby reducing the long-term oxygen production on the early Earth--as
      previously speculated--and contributing to the low concentrations of atmospheric
      oxygen during the late Archaean and early Proterozoic.

PMID- 12000957
TI  - Vestibular evidence for the evolution of aquatic behaviour in early cetaceans.
AB  - Early cetaceans evolved from terrestrial quadrupeds to obligate swimmers, a
      change that is traditionally studied by functional analysis of the postcranial
      skeleton. Here we assess the evolution of cetacean locomotor behaviour from an
      independent perspective by looking at the semicircular canal system, one of the
      main sense organs involved in neural control of locomotion. Extant cetaceans are
      found to be unique in that their canal arc size, corrected for body mass, is
      approximately three times smaller than in other mammals. This reduces the
      sensitivity of the canal system, most plausibly to match the fast body rotations
      that characterize cetacean behaviour. Eocene fossils show that the new sensory
      regime, incompatible with terrestrial competence, developed quickly and early in
      cetacean evolution, as soon as the taxa are associated with marine environments.
      Dedicated agile swimming of cetaceans thus appeared to have originated as a rapid
      and fundamental shift in locomotion rather than as the gradual transition
      suggested by postcranial evidence. We hypothesize that the unparalleled
      modification of the semicircular canal system represented a key 'point of no
      return' event in early cetacean evolution, leading to full independence from life
      on land.

PMID- 12000958
TI  - Allometric cascade as a unifying principle of body mass effects on metabolism.
AB  - The power function of basal metabolic rate scaling is expressed as aM(b), where a
      corresponds to a scaling constant (intercept), M is body mass, and b is the
      scaling exponent. The 3/4 power law (the best-fit b value for mammals) was
      developed from Kleiber's original analysis and, since then, most workers have
      searched for a single cause to explain the observed allometry. Here we present a
      multiple-causes model of allometry, where the exponent b is the sum of the
      influences of multiple contributors to metabolism and control. The relative
      strength of each contributor, with its own characteristic exponent value, is
      determined by the control contribution. To illustrate its use, we apply this
      model to maximum versus basal metabolic rates to explain the differing scaling
      behaviour of these two biological states in mammals. The main difference in
      scaling is that, for the basal metabolic rate, the O(2) delivery steps contribute
      almost nothing to the global b scaling exponent, whereas for the maximum
      metabolic rate, the O(2) delivery steps significantly increase the global b
      value.

PMID- 12000959
TI  - Host plants influence parasitism of forest caterpillars.
AB  - Patterns of association between herbivores and host plants have been thought to
      reflect the quality of plants as food resources as influenced by plant nutrient
      composition, defences, and phenology. Host-plant-specific enemies, that is, the
      third trophic level, might also influence the distribution of herbivores across
      plant species. However, studies of the evolution of herbivore host range have
      generally not examined the third trophic level, leaving unclear the importance of
      this factor in the evolution of plant-insect herbivore interactions. Analysis of
      parasitoid rearings by the Canadian Forest Insect Survey shows that parasitism of
      particular Lepidoptera species is strongly host-plant-dependent, that the pattern
      of host-plant dependence varies among species of caterpillars, and that some
      parasitoid species are themselves specialized with respect to tree species. Host
      plant-dependent parasitism suggests the possibility of top-down influence on host
      plant use. Differences in parasitism among particular caterpillar-host plant
      combinations could select for specialization of host plant ranges within
      caterpillar communities. Such specialization would ultimately promote the species
      diversification of Lepidoptera in temperate forests with respect to escape from
      enemies.

PMID- 12000960
TI  - Imperfect optics may be the eye's defence against chromatic blur.
AB  - The optics of the eye cause different wavelengths of light to be differentially
      focused at the retina. This phenomenon is due to longitudinal chromatic
      aberration, a wavelength-dependent change in refractive power. Retinal image
      quality may consequently vary for the different classes of cone photoreceptors,
      cells tuned to absorb bands of different wavelengths. For instance, it has been
      assumed that when the eye is focused for mid-spectral wavelengths near the peak
      sensitivities of long- (L) and middle- (M) wavelength-sensitive cones, short
      wavelength (bluish) light is so blurred that it cannot contribute to and may even
      impair spatial vision. These optical effects have been proposed to explain the
      function of the macular pigment, which selectively absorbs short-wavelength
      light, and the sparsity of short-wavelength-sensitive (S) cones. However, such
      explanations have ignored the effect of monochromatic wave aberrations present in
      real eyes. Here we show that, when these effects are taken into account, short
      wavelengths are not as blurred as previously thought, that the potential image
      quality for S cones is comparable to that for L and M cones, and that macular
      pigment has no significant function in improving the retinal image.

PMID- 12000961
TI  - Identification of a factor that links apoptotic cells to phagocytes.
AB  - Apoptotic cells are rapidly engulfed by phagocytes to prevent the release of
      potentially noxious or immunogenic intracellular materials from the dying cells,
      thereby preserving the integrity and function of the surrounding tissue.
      Phagocytes engulf apoptotic but not healthy cells, indicating that the apoptotic
      cells present a signal to the phagocytes, and the phagocytes recognize the signal
      using a specific receptor. Here, we report a factor that links apoptotic cells to
      phagocytes. We found that milk fat globule-EGF-factor 8 (MFG-E8), a secreted
      glycoprotein, was produced by thioglycollate-elicited macrophages. MFG-E8
      specifically bound to apoptotic cells by recognizing aminophospholipids such as
      phosphatidylserine. MFG-E8, when engaged by phospholipids, bound to cells via its
      RGD (arginine-glycine-aspartate) motif--it bound particularly strongly to cells
      expressing alpha(v)beta(3) integrin. The NIH3T3 cell transformants that expressed
      a high level of alpha(v)beta(3) integrin were found to engulf apoptotic cells
      when MFG-E8 was added. MFG-E8 carrying a point mutation in the RGD motif behaved
      as a dominant-negative form, and inhibited the phagocytosis of apoptotic cells by
      peritoneal macrophages in vitro and in vivo. These results indicate that MFG-E8
      secreted from activated macrophages binds to apoptotic cells, and brings them to
      phagocytes for engulfment.

PMID- 12000962
TI  - Dissection of COPI and Arf1 dynamics in vivo and role in Golgi membrane
      transport.
AB  - Cytosolic coat proteins that bind reversibly to membranes have a central function
      in membrane transport within the secretory pathway. One well-studied example is
      COPI or coatomer, a heptameric protein complex that is recruited to membranes by
      the GTP-binding protein Arf1. Assembly into an electron-dense coat then helps in
      budding off membrane to be transported between the endoplasmic reticulum (ER) and
      Golgi apparatus. Here we propose and corroborate a simple model for coatomer and
      Arf1 activity based on results analysing the distribution and lifetime of
      fluorescently labelled coatomer and Arf1 on Golgi membranes of living cells. We
      find that activated Arf1 brings coatomer to membranes. However, once associated
      with membranes, Arf1 and coatomer have different residence times: coatomer
      remains on membranes after Arf1-GTP has been hydrolysed and dissociated. Rapid
      membrane binding and dissociation of coatomer and Arf1 occur stochastically, even
      without vesicle budding. We propose that this continuous activity of coatomer and
      Arf1 generates kinetically stable membrane domains that are connected to the
      formation of COPI-containing transport intermediates. This role for Arf1/coatomer
      might provide a model for investigating the behaviour of other coat protein
      systems within cells.

PMID- 12000963
TI  - Microtubule basis for left-handed helical growth in Arabidopsis.
AB  - Left-right asymmetry in plants can be found in helices of stalks, stems and
      tendrils, and in fan-like petal arrangements. The handedness in these asymmetric
      structures is often fixed in given species, indicating that genetic factors
      control asymmetric development. Here we show that dominant negative mutations at
      the tubulin intradimer interface of alpha-tubulins 4 and 6 cause left-handed
      helical growth and clockwise twisting in elongating organs of Arabidopsis
      thaliana. We demonstrate that the mutant tubulins incorporate into microtubule
      polymers, producing right-handed obliquely oriented cortical arrays, in the root
      epidermal cells. The cortical microtubules in the mutants had increased
      sensitivity to microtubule-specific drugs. These results suggest that reduced
      microtubule stability can produce left-handed helical growth in plants.

PMID- 12000964
TI  - Cnd2 has dual roles in mitotic condensation and interphase.
AB  - Chromosome condensation requires condensin, which comprises five subunits. Two of
      these subunits--both being structural maintenance of chromosome (SMC) proteins
      are coiled-coils with globular terminal domains that interact with ATP and DNA.
      The remaining three, non-SMC subunits also have essential, albeit undefined,
      roles in condensation. Here we report that Cnd2 (ref. 6), a non-SMC subunit of
      fission yeast similar to Drosophila Barren and the budding yeast protein Brn1
      (refs 8, 9), is required for both interphase and mitotic condensation. In cnd2-1
      mutants, ultraviolet-induced DNA damage is not repaired, and cells arrested by
      hydroxyurea do not recover. A definitive defect of interphase is abolishment of
      Cds1 (a checkpoint kinase) activation in the presence of hydroxyurea in both cnd2
      1 mutant cells and in cells where other condensin subunits have been genetically
      disrupted. In the absence of hydroxyurea, a G2 checkpoint delay occurred in cnd2
      1 mutants in a manner dependent on Cds1 and ATM-like Rad3, but not Chk1 (refs 10
      13), before the mitotic condensation defect. Furthermore, cnd2-1 was synthetic
      lethal with mutations of excision repair, RecQ helicase and DNA replication
      enzymes. These interphase and mitotic defects provide insight into the
      mechanistic role of non-SMC subunits that interact with the globular SMC domains
      in the heteropentameric holocomplex.

PMID- 12000965
TI  - Bacteriophytochrome controls photosystem synthesis in anoxygenic bacteria.
AB  - Plants use a set of light sensors to control their growth and development in
      response to changes in ambient light. In particular, phytochromes exert their
      regulatory activity by switching between a biologically inactive red-light
      absorbing form (Pr) and an active far-red-light absorbing form (Pfr). Recently,
      biochemical and genetic studies have demonstrated the occurrence of phytochrome
      like proteins in photosynthetic and non-photosynthetic bacteria--but little is
      known about their functions. Here we report the discovery of a
      bacteriophytochrome located downstream from the photosynthesis gene cluster in a
      Bradyrhizobium strain symbiont of Aeschynomene. The synthesis of the complete
      photosynthetic apparatus is totally under the control of this
      bacteriophytochrome. A similar behaviour is observed for the closely related
      species Rhodopseudomonas palustris, but not for the more distant anoxygenic
      photosynthetic bacteria of the genus Rhodobacter, Rubrivivax or Rhodospirillum.
      Unlike other (bacterio)phytochromes, the carboxy-terminal domain of this
      bacteriophytochrome contains no histidine kinase features. This suggests a light
      signalling pathway involving direct protein-protein interaction with no
      phosphorelay cascade. This specific mechanism of regulation may represent an
      important ecological adaptation to optimize the plant-bacteria interaction.

PMID- 12000969
TI  - Transient aggregation of ubiquitinated proteins during dendritic cell maturation.
AB  - Dendritic cells (DCs) are antigen-presenting cells with the unique capacity to
      initiate primary immune responses. Dendritic cells have a remarkable pattern of
      differentiation (maturation) that exhibits highly specific mechanisms to control
      antigen presentation restricted by major histocompatibility complex (MHC). MHC
      class I molecules present to CD8(+) cytotoxic T cells peptides that are derived
      mostly from cytosolic proteins, which are ubiquitinated and then degraded by the
      proteasome. Here we show that on inflammatory stimulation, DCs accumulate newly
      synthesized ubiquitinated proteins in large cytosolic structures. These
      structures are similar to, but distinct from, aggresomes and inclusion bodies
      observed in many amyloid diseases. Notably, these dendritic cell aggresome-like
      induced structures (DALIS) are transient, require continuous protein synthesis
      and do not affect the ubiquitin-proteasome pathway. Our observations suggest the
      existence of an organized prioritization of protein degradation in stimulated
      DCs, which is probably important for regulating MHC class I presentation during
      maturation.

PMID- 12000970
TI  - Comparative assessment of large-scale data sets of protein-protein interactions.
AB  - Comprehensive protein protein interaction maps promise to reveal many aspects of
      the complex regulatory network underlying cellular function. Recently, large
      scale approaches have predicted many new protein interactions in yeast. To
      measure their accuracy and potential as well as to identify biases, strengths and
      weaknesses, we compare the methods with each other and with a reference set of
      previously reported protein interactions.

PMID- 12000971
TI  - Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 A resolution.
AB  - In bacteria, the binding of a single protein, the initiation factor sigma, to a
      multi-subunit RNA polymerase core enzyme results in the formation of a
      holoenzyme, the active form of RNA polymerase essential for transcription
      initiation. Here we report the crystal structure of a bacterial RNA polymerase
      holoenzyme from Thermus thermophilus at 2.6 A resolution. In the structure, two
      amino-terminal domains of the sigma subunit form a V-shaped structure near the
      opening of the upstream DNA-binding channel of the active site cleft. The carboxy
      terminal domain of sigma is near the outlet of the RNA-exit channel, about 57 A
      from the N-terminal domains. The extended linker domain forms a hairpin
      protruding into the active site cleft, then stretching through the RNA-exit
      channel to connect the N- and C-terminal domains. The holoenzyme structure
      provides insight into the structural organization of transcription intermediate
      complexes and into the mechanism of transcription initiation.

PMID- 12000972
TI  - Peroxisome proliferator-activated receptor ligands as antiatherogenic agents:
      panacea or another Pandora's box?
AB  - Peroxisome proliferator activated receptors (PPARs) are members of the nuclear
      receptor super family that modulate gene expression upon ligand activation. They
      are 3 major subtypes of PPARs: alpha, delta (also called beta), and gamma. PPAR
      gamma is widely expressed in the cardiovascular system and is involved in the
      regulation of tissue inflammation and smooth muscle cell growth pathways as well
      as in lipoprotein metabolism and coagulation cascades. PPAR-gamma ligands of
      (e.g., rosigitazone and pioglitazone) have been shown to exert antiatherogenic
      effects both in vitro and in vivo. PPAR-alpha ligands (e.g., clofibrate and
      benzofibrate) modulate lipoprotein metabolism, and affect inflammation and
      coagulation cascade. These effects may be helpful in resolving the dilemma
      arising from studies that showed significant mortality and morbidity benefits of
      fibrates in the face of minimal changes in HDL-cholesterol levels. The role of
      PPAR-delta in atherogenesis remains largely unknown, although it appears that
      PPAR-delta activation affects lipoprotein metabolism. PPAR ligands appear to be
      promising agents in limiting atherosclerosis; however, large-scale clinical
      trials are required to assess their safety and efficacy before they can be added
      to the clinicians' arsenal of antiatherosclerotic agents.

PMID- 12000973
TI  - Endothelin in health and disease: endothelin receptor antagonists in the
      management of pulmonary artery hypertension.
AB  - Endothelin (ET) has been identified as playing a fundamental role in many disease
      processes. Therapeutic efforts at interrupting ET's pathologic effects have
      focused on endothelin receptor antagonists (ERAs), of which two, bosentan and
      sitaxsentan, have been evaluated for the treatment of both primary and secondary
      pulmonary arterial hypertension (PAH). We discuss the multiple actions of ET, its
      role in various disease states, and the effects of ET receptor stimulation and
      blockade. Current classification and management of PAH are reviewed, along with
      the promise of greatly improved treatment generated by recent and ongoing
      clinical trials using ERAs.

PMID- 12000974
TI  - Delayed profound thrombocytopenia presenting 7 days after use of abciximab
      (ReoPro).
AB  - A case of a 65-year-old woman presenting with delayed profound thrombocytopenia 7
      days after the use of abciximab (ReoPro) in the setting of percutaneous coronary
      intervention is described. The patient had normal platelet counts for the first
      24 hours after the use of abciximab (ReoPro). She presented with petechiae and
      profound thrombocytopenia 1 week later. The patient was treated successfully with
      a platelet transfusion and recovered uneventfully. Profound thrombocytopenia
      occurs acutely within the first few hours after abciximab (ReoPro) use, so this
      case was unique in that the profound thrombocytopenia presented 1 week after use
      of abciximab (ReoPro).

PMID- 12000975
TI  - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by
      amiodarone: a report on two cases.
AB  - BACKGROUND: Amiodarone is an effective antiarrhythmic agent for life-threatening
      arrhythmias but has some noncardiac toxicity. The syndrome of inappropriate
      antidiuretic hormone secretion (SIADH) induced by amiodarone during long-term
      therapy seems to be rare among adverse effects. SUBJECTS AND RESULTS: We report
      on two elderly cases that developed hyponatremia caused by SIADH occurring during
      the initial loading period of amiodarone therapy. Both cases improved within 3
      weeks after reduction of the dose, although amiodarone was continued.
      CONCLUSIONS: Amiodarone-induced SIADH may occur during the initial loading
      period, and it may be improved by reduction of the dose without discontinuation
      of the drug.

PMID- 12000976
TI  - Acute effects of zatebradine on cardiac conduction and repolarization.
AB  - Zatebradine, a potent bradycardic agent, is believed to act selectively at the
      sinoatrial node. The selectivity of such a property relative to various
      electrophysiologic classes of action is not well defined. To characterize the
      electrophysiologic properties of zatebradine, the corrected sinus node recovery
      time, sinoatrial conduction time, conduction intervals, atrial effective
      refractory period and monophasic action potential duration in the ventricle were
      measured before and after incremental doses of zatebradine (0.1-1.5 mg/kg) in 15
      anesthetized dogs. The electrophysiologic effects of zatebradine developed
      immediately after a single i.v. bolus dose, reaching steady-steady-state at 15
      minutes with the maximum effect evident at 0.75 mg/kg. The IC(50) was 0.23 mg/kg.
      There was no significant effect on the sinus node recovery time. The PR interval
      on the electrocardiogram was significantly increased when the dose was higher
      than 0.25 mg/kg. The duration of the P wave and the PA interval were not changed.
      Zatebridine greatly increased the AH (from 135 to 178 milliseconds) without
      changing the HH and HV intervals in His bundle recordings. The EC(50) of this
      effect was 0.58 mg/kg. The QRS interval was not changed. The QTc was
      significantly increased from 0.43 to 0.56 s(1/2) (P < 0.05). The action potential
      duration was significantly increased by high dose zatebradine (> 0.5 mg/kg), the
      EC(50) for this effect was 0.76 mg/kg. The atrium effective refractory period was
      significantly increased (31%) with an EC(50) 0.69 mg/kg. These results indicate
      that zatebradine selectively inhibits sinus node automaticity at low doses. The
      inhibition of the AV nodal conduction and the lengthening of the refractory
      period and repolarization in the atria and the ventricles occur at higher dose.

PMID- 12000977
TI  - Torsade de pointes and sudden death induced by thiopental and isoflurane
      anesthesia in dogs with cardiac electrical remodeling.
AB  - BACKGROUND: Many anesthetic agents are known to have cardiac effects. The effects
      of pentobarbital, thiopental and isoflurane on dogs with electrical remodeling
      are lacking. METHODS AND RESULTS: We studied 12 dogs that underwent two
      anesthesias. First, anesthesia was induced (N=12) with intravenous thiopental (17
      mg/kg) induction followed by isoflurane inhalation (1.5%-3% via endotracheal
      tube). For electrical remodeling, we created complete atrioventricular block
      (CAVB) and myocardial infarction (MI). In 6 of the 12 dogs we also infused nerve
      growth factor (NGF) to the right stellate ganglion. All dogs had an implantable
      cardioverter-defibrillator (ICD) implanted. A second anesthesia was done 66 +/-
      20 days later. In 8 of the 12 dogs (6 without NGF), pentobarbital was used as the
      only anesthetic. In the remaining 4 dogs (all with NGF), 3 received thiopental
      and 1 received isoflurane. RESULTS: During the first anesthesia, none of 12 dogs
      had cardiac arrhythmia. During the second anesthesia, none of the 8 dogs that
      received pentobarbital developed ventricular fibrillation (VF). In contrast, all
      the dogs receiving either thiopental or isoflurane died of VF within 2 to 3
      minutes. QT and P-P intervals before VF were 440 +/- 36 milliseconds and 298 +/-
      28 milliseconds, longer and shorter (respectively) than those obtained the day
      prior to surgery (315 +/- 25 milliseconds, P < 0.001; 330 +/- 22 milliseconds, P
      < 0.01, respectively). CONCLUSION: Thiopental and isoflurane are not
      arrhythmogenic in normal dogs and dogs with acute MI and CAVB, but are extremely
      proarrhythmic in dogs with chronic MI and CAVB. Consistent with the results of in
      vitro studies, pentobarbital did not induce ventricular arrhythmia in dogs with
      cardiac electrical remodeling.

PMID- 12000978
TI  - The role of approximate entropy in predicting ventricular defibrillation
      threshold.
AB  - BACKGROUND: The role of myocardial tissue mass on ventricular defibrillation
      threshold (DFT) is unclear. We hypothesized that changes in tissue mass modulate
      DFT by changing ventricular fibrillation (VF) wavefront regularity (entropy).
      METHODS AND RESULTS: The right ventricles (RV) of seven farm pigs were isolated,
      superfused and perfused through the right coronary artery with oxygenated
      Tyrode's solution at 37 degrees C. The epicardial surface was stained with the
      voltage sensitive dye, di-4-ANEPPS, and activation wavefront numbers (AWN) during
      VF were determined from the optical maps using a CCD camera (96 x 96 pixels over
      a 3.5 x 3.5 cm area). The RV mass was progressively reduced by sequential cutting
      of 1 to 2 g of tissue (approximately 12 cuts in total) distal to the perfusion
      site. After each cut, VF was reinduced, optical maps obtained, and the 50%
      probability of successful DFT(50) determined using an up-down algorithm. After
      each cut, the approximate entropy (ApEn) was also computed using 5 seconds of VF
      data obtained with a bipolar electrode and a pseudo-electrocardiogram. Tissue
      mass reduction of up to one third of the RV mass (ie, from 48.4 +/- 4.25 g to 34
      +/- 4.7 g) caused little or no change in the DFT, ApEn or AWN. However, further
      progressive reduction of the RV mass near the critical mass of VF resulted in a
      significant (P < 0.05) progressive decrease in all three measured parameters. DFT
      energy was reduced by 27% (1.47 +/- 0.34 J vs. 1.02 +/- 0.14 J). There was a
      significant (P < 0.01) correlation between the DFT and ApEn, which significantly
      further increased (P < 0.001) near the critical mass. In a separate series of 6
      isolated RVs, the ApEn correlated well with the Kolmogorov-Sinai (K-S) entropy,
      the standard method of calculating entropy. CONCLUSION: Tissue mass reduction
      significantly reduces DFT when the mass reduction increases VF wavefront
      regularity.

PMID- 12000979
TI  - Blockade of 5-HT(2A) receptors by sarpogrelate protects the heart against
      myocardial infarction in rats.
AB  - BACKGROUND: It has been shown that serotonin (5-hydroxytryptamine, 5-HT) is
      involved in exacerbating vascular abnormalities; however, its role in mediating
      changes in cardiac function due to myocardial injury has yet to be established.
      This study examined the effect of sarpogrelate, a 5-HT(2A) receptor blocker, in
      preventing cardiac dysfunction due to myocardial infarction (MI). METHODS AND
      RESULTS: Rats were treated 3 days before surgery with or without 5 mg x kg(-1) x
      day(-1) sarpogrelate, and the left coronary artery was ligated for 3 weeks to
      induce MI. Sarpogrelate reduced the mortality from 40% to 30%, infarct size from
      35% to 25%, and left ventricular end diastolic pressure from 15 mm Hg to 10 mm Hg
      in MI rats. Electrocardiographic (ECG) tracings showed a marked deviation in the
      ST-segment and prolongation of the QTc interval in MI rats during the 3 weeks;
      these changes were attenuated by sarpogrelate pretreatment. In another set of
      experiments, MI rats were treated with 5 mg x kg(-1) x day(-1) sarpogrelate 1
      hour after the surgery, and the hemodynamic and electrocardiograph changes were
      assessed at 3 weeks. This posttreatment was also found to reduce infarct size,
      improve cardiac function, and attenuate ECG changes. CONCLUSIONS: Sarpogrelate
      attenuates cardiac dysfunction, infarct size, and changes in the ECG due to MI.
      These results also support the view that serotonin and 5-HT(2A) may contribute to
      the deleterious effects of ischemic injury in the heart.

PMID- 12000981
TI  - Laparoscopic fundoplication. Is there a correlation between pH studies and the
      patient's quality of life? Why should we evaluate quality of life data!?

PMID- 12000982
TI  - The effects of laparoscopic antireflux surgery on GERD patients with concomitant
      anxiety disorders.

PMID- 12000983
TI  - Role of dopamine in renal dysfunction during laparoscopic surgery.
AB  - BACKGROUND: Sympathetic vascular insult and hemodynamic changes represent the
      most reliable explanation of renal impairment resulting from acute intraabdominal
      pressure. We evaluated the effects of low-dose dopamine administration during a
      long-lasting surgical laparoscopic procedure. METHODS: For this study 40,
      patients submitted to a colorectal laparoscopic procedure with 15 mmHg of
      intraabdominal pressure were randomly allocated to two groups: 20 receiving 2
      mg/kg/min of dopamine and 20 receiving the same perfusion of saline. Hemodynamic
      parameters, renal function, urinary output, and creatinine clearance, were
      studied. RESULTS: The hemodynamic parameters were similar in both groups. The
      urinary output decreased during the intraoperative period only the saline group
      (p = 0.4). Then 2 h postoperatively, it increased in both groups, and no
      statistically significant differences were found between the groups. The
      creatinine clearance decreased in both groups during the intraoperative time, but
      it was worse in the saline group (-28 +/- 120 vs -194 +/- 106; p = 0.022). During
      the postoperative period, both groups showed improvement, but in control group
      the values remained lower than at baseline (p = 0.04), and significantly lower
      than in the dopamine group (230 +/- 337 vs 100 +/- 192; p = 0.012). CONCLUSIONS:
      An intrabdominal pressure of 15 mmHg induces a time-limited renal dysfunction,
      and low doses of dopamine could prevent this undesirable effect.

PMID- 12000984
TI  - Laparoscopic cholecystectomy and common bile duct exploration are safe for older
      patients.
AB  - BACKGROUND: Laparoscopic common bile duct (CBD) exploration is a well-established
      treatment option in dedicated centers. However, few data are available on the
      results in elderly patients. METHODS: The outcome after laparoscopic CBD
      exploration in elderly patients (age <70 years) was compared with that in a
      concurrent control group of younger patients (age, <70 years). RESULTS: There
      were 77 elderly patients in group A and 207 younger patients in group B. American
      Society of Anesthesiology (ASA) III and IV patients and prior abdominal
      operations were more frequent in group A (p <0.001). Two patients from each group
      underwent conversion to open surgery. There was no significant difference
      frequency of use between the transcystic and choledochotomy approaches, although
      the latter tended to be more frequent in the group A because of larger stones,
      (group A 53.4%; group B, 37.6%). Minor and major morbidity (group A, 12%; group
      B, 13.6%), rate of recurrent stones (group A, 1.3%; group B, 1.9%), and mortality
      (group A, 1.3%; group B, 0%) were not significantly different between the two
      groups. The single death in group A involved a patient with acute toxic
      cholangitis who underwent emergency surgery after multiple failed attempts at
      endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy
      performed elsewhere. No CBD stenosis was observed at follow-up assessment.
      CONCLUSIONS: Elective laparoscopic CBD exploration is safe and effective. It may
      become the standard of care in both elderly and younger patients.

PMID- 12000985
TI  - A systems approach to surgical safety.

PMID- 12000986
TI  - Susceptibility of Brazilian staphylococcal strains to glycopeptides evaluated by
      different testing methods.
AB  - Reports of staphylococci with reduced susceptibility to glycopeptides are cause
      for concern. This study evaluated the susceptibility of 84 staphylococci clinical
      isolates to glycopeptides by the disk diffusion, agar dilution, E-test, and BHIA
      screening methods. Vancomycin agar dilution showed all strains presented minimum
      inhibitory concentration (MIC) ranging from 0.5 to 2 microg/ml, and the E-test
      showed similar results. Teicoplanin agar dilution test showed MICs ranging from <
      or = 0.5 to 2 microg/ml for Staphylococcus aureus and MICs ranging from <0.25 to
      32 microg/ml for coagulase-negative Staphylococcus (CNS). Ten CNS isolates
      presented MICs ranging from 8 to 32 microg/ml for agar dilution and/or E-test.
      All the staphylococci were susceptible to vancomycin by the disk diffusion test
      (DDT), but two CNS isolates presented intermediate resistance to teicoplanin by
      the DDT and MICs of susceptibility, with two other CNS strains, teicoplanin
      susceptible by the DDT, presented MICs of intermediate resistance. On the
      vancomycin-containing agar, 20 CNS isolates were able to grow, but no S. aureus
      strain. All these isolates showed MICs to teicoplanin (4-32 microg/ml) higher
      than those isolates that did not grow on the agar screen plate. PFGE of
      chromosomal SmaI digests showed a wide diversity of these CNS strains, without
      any predominance of a single PFGE pattern.

PMID- 12000987
TI  - Secretion of beta-1,3-glucanases by the yeast Pichia membranifaciens and its
      possible role in the biocontrol of Botrytis cinerea causing grey mold disease of
      the grapevine.
AB  - Pichia membranifaciens strain FY-101, isolated from grape skin, was found to be
      antagonistic to Botrytis cinerea, the causal organism of the grey mold disease of
      the grapevine. When grown together on solid as well as in liquid media, the yeast
      brings about the inhibition of Botrytis cinerea, which in turn loses its ability
      to produce the grey mold symptoms on the grapevine plantlets. The secretion of
      beta-1,3-glucanases by P. membranifaciens is one of the possible mechanisms
      related to this antagonism. In vitro experiments confirm that this yeast can be
      used as a biological control organism against B. cinerea. An account of this
      antagonism and the production of beta-1,3-glucanases by P. membranifaciens is
      given here.

PMID- 12000988
TI  - Plant growth-promoting rhizobacteria-mediated induction of phenolics in pea (
      Pisum sativum) after infection with Erysiphe pisi.
AB  - Qualitative and quantitative estimation of phenolic compounds was done through
      high performance liquid chromatography (HPLC) in different parts of pea ( Pisum
      sativum) after treatment with two plant growth-promoting rhizobacteria (PGPR),
      viz., Pseudomonas fluorescens (strain Pf4) and Pseudomonas aeruginosa (referred
      to here as Pag) and infection by Erysiphe pisi. The phenolic compounds detected
      were tannic, gallic, ferulic, and cinnamic acids on the basis of their retention
      time in HPLC. In all the treated plants, synthesis of phenolic compounds was
      enhanced. The induction of gallic, ferulic, and cinnamic acids was manyfold more
      than those in the control. Maximum accumulation of phenolic compounds was
      observed in plants raised from PGPR-treated seeds and infection with E. pisi.
      Under pathogenic stress, Pag performed better because a relatively higher amount
      of phenolics was induced compared with plants treated with Pf4.

PMID- 12000989
TI  - Purification and characterization of an esterase from Acinetobacter lwoffii I6C
      1.
AB  - EstA was purified from the supernatant by A. lwoffii 16C-1. Its molecular mass
      was determined to be 45 kDa, and the optimal activity occurred when the pH level
      was 8.0 at a temperature of 37 degrees C. The activation energies for the
      hydrolysis of p-nitrophenyl butyrate was determined to be 11.25 kcal/mol in the
      temperature range of 10-37 degrees C. The enzyme was unstable at temperatures
      higher than 50 degrees C. The Michaelis constant ( K(m)) and V(max) for p
      nitrophenyl butyrate were 11 mocroM and 131.6 mocroM min(-1) mg of protein-1,
      respectively. The enzyme was strongly inhibited by Hg(2-), Ca(2+), Mg(2+),
      Fe(2+), Cu(2+), Zn(2+), Mn(2+), Co(2+), ethylemediaminetetraacetic acid (EDTA),
      phenylmethylsulfonyl fluoride (PMSF), and diisopropyl fluorophosphate (DFP).

PMID- 12000990
TI  - Methanogenesis from furfural by defined mixed cultures.
AB  - Methanogenesis from furfural by defined mixed cultures was studied. Under sulfate
      reducing conditions, a Desulfovibrio strain was used as the furfural-degrading
      species producing acetic acid. This sulfate-reducing bacterium (SRB)
      Desulfovibrio strain B is an incomplete oxidizer, unable to carry out the
      terminal oxidation of organic substrates, leaving acetic acid as the end product.
      Introduction of acetate-utilizing methanogenic archaeon Methanosarcina barkeri
      227 converted acetic acid to methane. This well-defined mixed consortium used
      furfural as its sole source of carbon and converted it to methane and CO(2). In
      the mixed culture, when a methanogen inhibitor was used in the culture medium,
      furfural was converted to acetic acid by the Desulfovibrio strain B, but acetic
      acid did not undergo further metabolism. On the other hand, when the growth of
      Desulfovibrio in the consortium was suppressed with a specific SRB inhibitor,
      namely molybdate, furfural was not degraded. Thus, the metabolic activities of
      both Desulfovibrio strain B and M. barkeri 227 were essential for the complete
      degradation of furfural.

PMID- 12000991
TI  - NaCl-induced oxidative damage in the cyanobacterium Anabaena doliolum.
AB  - Results obtained with graded concentrations of NaCl (20-200 m M) show decrease in
      the chlorophyll 'a' contents of Anabaena with increasing concentration of NaCl
      except at extremely low concentration of NaCl (5-20 m M). The rate of Hill
      activity and oxygen evolution are found to be stimulated by lower concentrations
      of NaCl, but not at higher concentrations of NaCl. Results have demonstrated that
      the O(2) evolution process is relatively more sensitive to NaCl stress than the
      Hill activity. Further, the results show NaCl induced an increase in the rate of
      RNO bleaching and loss of total thiol (-SH) contents. Taken together, these
      results suggest a NaCl-induced general oxidative stress. Results on the effect of
      oxygen radical quenchers reveal a predominant role of singlet oxygen in the NaCl
      induced general oxidative stress as evident from a higher quenching effect of
      sodium azide than formate and histidine on the rate of RNO bleaching in Anabaena
      cells. However, the rate of lipid peroxidation and SOD activity show a declining
      pattern in response to increasing concentrations of NaCl. There is the
      possibility of a NaCl-induced decrease in the rate of lipid peroxidation when the
      SOD activity is also lower. But the NaCl-induced decline in the SOD activity does
      suggest that symptoms of general oxidative stress at elevated levels of NaCl are
      apparently owing to collapse of intracellular defense of the cells against the
      toxic oxygen radicals, not because of the higher rate of photosynthetic activity.

PMID- 12000992
TI  - Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by
      azithromycin and erythromycin.
AB  - Azithromycin is an important antibiotic for the treatment of several different
      Gram-positive and Gram-negative bacterial infections. Erythromycin and
      clarithromycin are less useful antibiotics against Gram-negative infections. This
      difference in inhibitory activity was explored by comparing the effects of
      azithromycin and erythromycin on cellular functions in Haemophilus influenzae
      cells. Effects of both antibiotics on translation, cell viability, and growth
      rates have been measured. An IC(50) of 0.4 microg/ml was found for the effects of
      azithromycin on each of these processes. For erythromycin, an IC(50) of 1.5
      microg/ml was observed, indicating a fourfold lower sensitivity of the organisms
      to this compound. The features of a second target for macrolide antibiotic
      inhibition in H. influenzae cells have also been examined. Inhibition of the
      synthesis of the large 50S ribosomal subunit was measured. Subunit formation was
      prevented in a concentration dependent fashion, with azithromycin showing a
      ninefold greater effect on this process compared with erythromycin. Synthesis of
      the 30S ribosomal subunit was not effected. Pulse and chase labeling kinetics
      confirmed the slower synthesis rate of the 50S particle in the presence of each
      antibiotic. The results are discussed in terms of the stronger effect of
      azithromycin on ribosome biosynthesis in this organism.

PMID- 12000993
TI  - Tight regulation and modulation via a C1-regulated promoter in Escherichia coli
      and Pseudomonas aeruginosa.
AB  - We describe the development and analysis of a novel promoter system regulated by
      the bacteriophage P1 temperature-sensitive C1 repressor. Using transcriptional
      fusions to the lacZ reporter gene to monitor gene expression, we show that the
      ratio of induction/repression can be up to 1500-fold in Escherichia coli. The
      promoters exhibited extremely tight repression and could be modulated over a
      range of temperatures. The utility of the promoter system was tested in
      Pseudomonas aeruginosa. C1 effectively repressed transcription; however, only
      modest induction was achieved. To increase the levels of induction, the amount of
      c1 was modulated at the mRNA level by using a LacI-regulated promoter. This
      resulted in a 59-fold induction in gene expression under inducing conditions. As
      the promoter system was constructed in a broad-host range vector and utilized the
      C1 repressor from a broad-host range phage, the system will provide the potential
      for controlled gene expression in Gram-negative bacteria.

PMID- 12000994
TI  - Electron microscopic studies of three gliding Mycoplasmas, Mycoplasma mobile, M.
      pneumoniae, and M. gallisepticum, by using the freeze-substitution technique.
AB  - Freeze-substitution technique was applied to thin-sectioning electron microscopy
      of Mycoplasma mobile, M. pneumoniae, and M. gallisepticum, all of which can glide
      in the direction of the tapered cell end. M. mobile presented a flask-like cell
      morphology. An additional layer was found around the tapered end. The cell images
      of M. pneumoniae showed a protruding membrane extension, the attachment
      organelle, composed of a low density space inside the cells and featuring a
      filamentous dense core anchored to the terminal end. The detailed structures were
      more obvious than those observed by the conventional chemical fixation. The cells
      of M. gallisepticum presented irregular dense granules, in contrast to regular
      particles, which can be observed in the images of chemically fixed thin sections,
      in the rear portion of the cells.

PMID- 12000995
TI  - Effects of exogenous ammonia or free amino acids on proteolytic activity and
      protein breakdown products in Streptococcus bovis, Prevotella albensis, and
      Butyrivibrio fibrisolvens.
AB  - We studied in details the ammonia or free amino acids (AA) effects on proteolytic
      activity of three ruminal bacteria: enzymatic activities and protein breakdown
      products were measured at the end of the exponential growth phase. In
      Streptococcus bovis the simultaneous uptake of ammonia and probably small
      peptides induced a decline in total proteolytic activity as a result of changes
      in endopeptidasic activities. With free AA, the tendency for the endopeptidasic
      activities to specialise was more evident and the total proteolytic activity
      decreased too. In Prevotella albensis, the inhibition of proteolysis with free AA
      was linked to the disappearance of free endopeptidases, to the specialization of
      cell-associated endopeptidases and to the decrease in exopeptidases. The decrease
      of proteolysis in P. albensis when ammonia was added was more difficult to
      interpret. With ammonia or AA Butyrivibro fibrisolvens developed a distinct
      behavior of those expressed by the other species: the increase of the total
      proteolytic activity could be explained by a better balance of the endopeptidases
      expressed. It then clearly appeared that the expression of the proteolytic
      activities are linked to the nature and/or to the quantity of the nitrogen
      source. This leads each species to adopt its own nutritional strategy in order to
      adapt to the environmental conditions of the ruminal ecosystem.

PMID- 12000996
TI  - Molecular tools for speciation and epidemiological studies of Acanthamoeba.
AB  - Current diagnostic methods for Acanthamoeba identification rely heavily on light
      microscopic techniques that do not provide sufficient information about the
      identification of Acanthamoeba at the species level, thus delaying accurate
      identification of the infective agent. Here we report the use of polymerase chain
      reaction (PCR)-based restriction enzyme analyses to detect and speciate
      Acanthamoeba from both clinical and environmental sources by comparing their
      restriction endonuclease patterns. Significant diversity was observed between and
      within morphologically defined Acanthamoeba species. The usefulness of PCR-based
      assays and other available diagnostic methods is discussed.

PMID- 12000997
TI  - Isolation and screening of brittlestar-associated bacteria for antibacterial
      activity.
AB  - Many microbes associated with marine organisms have antimicrobial activity. We
      report the isolation of bacteria associated with Amphipholis gracillima that have
      broad-spectrum antibacterial activity against a number of common bacterial
      strains. Fifty-eight isolates of bacilli obtained from A. gracillima arm
      homogenates, from excised wound tissue, or from swabs of arm stumps exhibited 20
      100% inhibition of one or more of 16 test bacteria at 35% salinity. Forty-one of
      the isolates were capable of 20-100% inhibition of one or more of 19 subject
      bacteria at 10% salinity at 37 degrees C. Three isolates, BE37, BE52, and BE53,
      exhibited the greatest range of antibacterial activity at both 10% and 35%
      salinity. Our results suggest that some of the bacteria associated with A.
      gracillima may provide the animal with chemical defenses against adverse
      bacterial infection. The water-soluble inhibitory chemicals produced by the
      bacteria could potentially function as antimicrobial compounds against human
      pathogenic bacteria.

PMID- 12001000
TI  - Arachidonic acid-derived bioactive lipids: their role and the role for their
      inhibitors in dermatology.
AB  - BACKGROUND: In addition to corticosteroids, there are increasing numbers of anti
      inflammatory agents that specifically target bioactive lipids generated from
      arachidonic acid. Knowledge of the diverse mechanisms of action of these
      different bioactive lipids holds promise in the therapy of a wide spectrum of
      cutaneous and systemic disorders. OBJECTIVE: Therapeutic manipulations of these
      lipid molecules through inhibition, stimulation, or direct replacement have broad
      physiologic effects. These therapeutic strategies not only modulate inflammation,
      pain, and hemostatic parameters, they also play a role in cardiac, respiratory,
      renal, and gastrointestinal function and disease, as well as in angiogenesis and
      in factors that control cell growth and apoptosis important in carcinogenesis.
      CONCLUSION: Newer drug discovery methods, including combinatorial chemistry with
      molecular modeling, have made it possible to develop inhibitors and analogs with
      increasing specificity and bioactivity and decreasing toxicity. Although the
      application of these analogs and inhibitors for cutaneous disease is limited
      today, either as primary agents or adjuvant therapy, these drugs will have a
      place in our therapeutic regimes of the future. We present a review of the
      therapeutic agents now available from manipulation of these bioactive lipids, and
      their role and future in dermatology.

PMID- 12001001
TI  - Peripheral T cell lymphoma presenting as dermatomyositis-like eruption.
AB  - BACKGROUND: There are several conditions reported to mimic the cutaneous
      manifestations of dermatomyositis, including lymphoproliferative disorders.
      OBJECTIVE: This case report presents an unusual case of peripheral T cell
      lymphoma mimicking dermatomyositis and discusses the clinical and pathologic
      features that distinguish it from dermatomyositis. METHODS AND RESULTS: A 62-year
      old woman presented with a two-month history of a progressive painful cutaneous
      eruption and interstitial infiltrates on chest x-ray. Skin biopsy revealed
      peripheral T cell lymphoma. The diagnosis was confirmed by lung biopsy.
      CONCLUSIONS: Although rare, a lymphoproliferative disorder must be included in
      the differential diagnosis of a cutaneous dermatomyositis-like eruption.

PMID- 12001002
TI  - Granuloma gluteale adultorum associated with use of topical benzocaine
      preparations: case report and literature review.
AB  - BACKGROUND: Granuloma gluteale infantum is a skin disorder of controversial
      etiology manifested clinically by oval reddish-purple granulomatous nodules on
      the gluteal surfaces and groin areas of infants. Similar granulomas are noted in
      adults and the elderly and are referred to as granuloma gluteale adultorum and
      diaper area granuloma of the aged, respectively. Occlusion from diapers, paper
      napkins, plastic pants, detergents, starch, powder, halogenated steroids,
      candidal infection, and urine and feces are postulated as possible etiologies.
      OBJECTIVE: We report a case of a 40-year-old woman presenting with a 3-year
      history of multiple, painful, closely set, red-purple, oval, smooth, firm papules
      and nodules in the genitocrural area. The development of the lesions was
      associated with prolonged use of topical benzocaine. Histology of the lesions was
      consistent with granuloma gluteale infantum. Gram stain and culture of
      representative tissue did not demonstrate bacterial or fungal organisms. The
      lesions significantly improved with discontinuation of topical benzocaine. Patch
      testing of skin to determine allergic contact hypersensitivity to benzocaine was
      negative. CONCLUSION: We propose that topical benzocaine preparations may play a
      role in the pathogenesis of granuloma gluteale adultorum, independent of contact
      sensitization to benzocaine.

PMID- 12001003
TI  - Using the internet to assess and teach medical students in dermatology.
AB  - BACKGROUND AND OBJECTIVES: We wish to develop and evaluate a user-friendly online
      interactive teaching and examination model as an adjunct to traditional bedside
      teaching of medical students during a clinical rotation in dermatology. METHODS:
      Following completion of an online examination, senior medical students at the
      University of British Columbia (n = 178) were asked to complete an online survey
      to evaluate their acceptance of this new method. The online examination model was
      evaluated through students' responses to the questionnaire-based evaluation they
      were asked to complete following their examination. Responses were evaluated on a
      standardized 5-point scale. RESULTS: A high response rate was achieved (98.9%).
      Overall, 93% of senior medical students felt that the Internet was a useful and
      effective way to administer a dermatology examination. Most (90%) preferred the
      online examination to a traditional paper-and-pencil examination and the majority
      (88%) felt that the quality of digital images presented was sufficient to make an
      accurate diagnosis. In addition, students strongly supported the further
      development of teaching resources on the web and would use these resources in
      learning dermatology (93%). CONCLUSIONS: The development of an online interactive
      examination tool for dermatology is technically feasible with current technology.
      Senior medical students are not only accepting of this new technology but also
      prefer it to more traditional formats and indicate enthusiasm for the development
      of further online teaching resources in dermatology.

PMID- 12001004
TI  - Use of eye movement desensitization and reprocessing (EMDR) in the treatment of
      dermatologic disorders.
AB  - BACKGROUND: The use of psychological therapies in dermatology is being
      increasingly recognized because stress and negative emotions are major factors in
      a wide range of dermatologic disorders. Eye movement desensitization and
      reprocessing (EMDR) is a relatively new psychological intervention which was
      first described to be effective in post-traumatic stress disorder, a condition
      associated with extremely stressful life situations. OBJECTIVE: We evaluated the
      efficacy of EMDR in primary dermatologic disorders where psychological stress
      plays an important part in the pathogenesis of the disorder, and in clinical
      situations where the dermatologic symptom is the feature of a stress-related
      psychiatric disorder. METHODS: Four patients (two patients with atopic dermatitis
      and psoriasis, respectively, whose symptoms were exacerbated by stress, one
      patient with acne excoriee associated with body image pathology as a result of
      childhood emotional abuse, and one patient with generalized urticaria associated
      with post-traumatic stress disorder) were treated using the standard EMDR
      protocol with 3-6 sessions for a period ranging from 4 to 12 weeks, and followed
      up for 6-12 months after the end of EMDR therapy. RESULTS: All 4 patients
      experienced a marked improvement in their symptoms after 3-6 sessions of EMDR,
      within a period of </= 3 months, and maintained improvement during followup
      periods of 6-12 months. CONCLUSION: Our preliminary findings suggest that EMDR
      may be beneficial in the treatment of a wide range of stress-mediated
      dermatologic symptoms.

PMID- 12001005
TI  - 6-thioguanine in the treatment of psoriasis: a case report and literature review.
AB  - BACKGROUND: 6-Thioguanine is a purine analog primarily indicated for acute
      myelogenous leukemia. Its use in psoriasis was first investigated in the 1950s
      and current interest in serious treatments for psoriasis, such as cyclosporine,
      has renewed interest in this medication. Newer therapies, such as PUVA and
      retinoids, have side effects as do some older treatments, such as methotrexate,
      which fell into favor at the same time 6-thioguanine was being investigated.
      Reexamining older treatments can open up new therapeutic options in difficult
      cases. OBJECTIVE: The goal of this article is to provide a comprehensive review
      of the literature regarding the use of 6-thioguanine in the treatment of
      psoriasis as well as an illustrative case report demonstrating the use and side
      effects of 6-thioguanine in a patient with pustular psoriasis. Topics reviewed
      include efficacy, side effects, laboratory monitoring, different dosing regimens,
      and proposed mechanisms of action. CONCLUSIONS: 6-Thioguanine has been highly
      effective in treating and maintaining improvement in patients with psoriasis. A
      study comparing efficacies with methotrexate would be extremely useful. Because
      of the possibility of severe bone marrow depression, 6-thioguanine is not a first
      line treatment. However, with new dosing regimens, proper laboratory monitoring,
      and further studies, use of 6-Thioguanine could expand in the future.

PMID- 12001006
TI  - Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF
      15 in treatment of rosacea.
AB  - BACKGROUND: Rosacea is a photoaggravated dermatosis responsive to treatment with
      topical and oral antibiotics. A formulation combining metronidazole 1% cream with
      sunscreen SPF 15 was developed for the treatment of rosacea. OBJECTIVE: The
      objective of this study was to determine the safety and efficacy of a formulation
      combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of
      moderate to severe rosacea. METHODS: One hundred and twenty patients with
      moderate to severe rosacea were enrolled for a randomized, placebo-controlled
      (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was
      applied twice daily to the entire face over a 12-week period. RESULTS: Treatment
      with metronidazole 1% cream with sunscreen SPF 15 resulted in significant
      improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae
      scores, and investigator and patient global assessment scores compared with
      baseline and placebo. Adverse reactions related to study medication were
      typically mild, occurred at the site of application, and were reversible. There
      was no difference between the safety profiles of metronidazole 1% cream with
      sunscreen SPF 15 and placebo. CONCLUSIONS: The combined topical formulation of
      metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated
      topical agent for the treatment of moderate to severe rosacea.

PMID- 12001007
TI  - Tea consumption and iron status.
AB  - OBJECTIVE: To give an overview of the association between tea consumption and
      iron status. METHODS: A PUBMED search was performed (up to June 2001) for all
      publications containing the words: tea and ferritin, h(a)emoglobin, iron status
      or an(a)emia. Sixteen studies were evaluated in groups with high (infants,
      children and premenopausal women) or low prevalence of iron deficiency (men and
      the elderly). RESULTS AND DISCUSSION: Of the 16 studies reviewed, six included
      infants and children, six premenopausal women, two men and two the elderly. In
      study groups with high prevalence of iron deficiency, tea consumption was
      inversely associated with serum ferritin and/or haemoglobin. The association
      disappeared when adjusting for confounding (dietary) factors, except for one
      study including 40% of iron deficient women. In groups with low prevalence of
      iron deficiency, tea consumption was not inversely associated with serum ferritin
      and/or haemoglobin. In those at risk for iron overload, such as middle-aged men,
      tea consumption may lower serum ferritin concentrations as reported in one study.
      This finding awaits further confirmation. CONCLUSION: This overview shows that
      tea consumption does not influence iron status in Western populations in which
      most people have adequate iron stores as determined by serum ferritin
      concentrations. Only in populations of individuals with marginal iron status does
      there seem to be a negative association between tea consumption and iron status.

PMID- 12001008
TI  - Vitamin B6 intakes and status of mechanically ventilated critically ill patients
      in Taiwan.
AB  - OBJECTIVE: To assess vitamin B6 intake and status of critically ill patients. The
      relationship between vitamin B6 status indicators and the severity of illness and
      outcome in these patients was also examined. DESIGN: Prospective clinical study.
      SETTING: The study was performed at the Taichung Veteran General Hospital, in the
      central part of Taiwan. SUBJECTS: Ninety-four patients in the intensive care unit
      (ICU) entered the study and 46 patients successfully completed this study.
      INTERVENTIONS: No intervention. MAIN OUTCOME MEASURES: Vitamin B6 intake was
      recorded for 14 days. Vitamin B6 status was assessed by direct measures (plasma
      pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and urinary 4-pyridoxic acid (4
      PA)) and indirect measures (erythrocyte alanine (EALT-AC) and aspartate (EAST-AC)
      aminotransaminase activity coefficient). The severity of illness (APACHE II
      score), the length of ventilation dependency, and the length of ICU and hospital
      stay were recorded. RESULTS: Patients had an adequate mean vitamin B6 intake
      (16.26+/-19.39 mg) during the 14 day study. Mean vitamin B6 intake was
      significantly higher on day 14 than on day 1 (P<0.001). However, plasma PLP and
      PL concentrations significantly decreased at the 14th day after admission
      (P<0.05). Erythrocyte alanine aminotransaminase activity coefficient and EAST-AC
      did not change significantly. Urinary 4-PA significantly increased at the 14th
      day (P<0.001). No significant relationships were found between APACHE II scores
      and clinical outcomes (the length of ICU and hospital stay, the length of
      ventilation dependency) of patients, vitamin B6 intake or status indicators.
      CONCLUSIONS: Critically ill patients received nutritional support in the ICU, and
      had sufficient mean vitamin B6 intake and adequate vitamin B6 status. Therefore,
      the severity of illness and the results should not be affected by vitamin B6
      status. However, we have noted that plasma PLP and PL concentrations
      significantly decreased while vitamin B6 intake significantly increased on day
      14. Critical clinical conditions and complex metabolism in the critically ill may
      account for the reduction of plasma PLP and PL. Since vitamin B6 deficiency
      causes profound effects on immune system function, dietary or supplemented
      vitamin B6 intake is suggested for hospitalized patients.

PMID- 12001009
TI  - Ten-year trends of dietary intake in a middle-aged French population:
      relationship with educational level.
AB  - OBJECTIVE: To compare dietary intakes at a 10 y interval of a population aged 35
      64 living in France. Trends in nutrient intake and food consumption were examined
      with a special emphasis on the relationships between educational level and
      dietary behaviour. DESIGN: Two independent surveys conducted in 1985-1987 (S1)
      and 1995-1997 (S2) in the framework of the WHO MONICA project. Dietary intake was
      assessed with a 3-day record method and a food frequency questionnaire. The
      samples analysed included 416 men and 446 women for S1, 393 men and 409 women for
      S2. RESULTS: A significant improvement of the quality of fat intake was observed
      between S1 and S2, independently of educational level, with an increase of the
      age adjusted P/S ratio from 0.42 to 0.50 in men (P=10(-4)) and from 0.41 to 0.50
      in women (P=10(-4)), whereas the daily cholesterol intake dropped from 552.0 to
      466.9 mg and from 447.2 to 384.6 mg in men and women, respectively (P=10(-4)).
      These variations were associated with a decrease in the consumption of high-fat
      foods and an increase in that of low-fat products (poultry, low-fat dairy foods,
      fish) in all educational classes. By contrast, the consumption of fruit and
      vegetables, which was highly associated with educational level, varied little
      over time. CONCLUSIONS: Our results indicate slight improvement in fat quality,
      independently of educational level, while fruit and vegetable intake, which
      appeared more dependent on educational level, was only poorly modified over the
      10 y interval.

PMID- 12001010
TI  - Selenium intakes in 18-64-y-old Irish adults.
AB  - OBJECTIVE: To measure the intake of selenium (Se) and the contribution of
      different food groups to Se intake in adults aged 18-64 y in Ireland. The
      adequacy of Se intake in the population is also assessed. DESIGN: Food
      consumption was estimated using a 7 day food diary for a representative sample
      (n=1379; men=662, women=717) of 18-64-y-old Irish adults selected randomly from
      the electoral register. Se intake was estimated using updated tables of food
      composition. RESULTS: Mean daily Se intakes (+/-s.d.) from all sources (ie food
      plus supplements), and from food sources alone, for the group of Irish adults
      aged 18-64 y were 52 (+/-23) and 50 (+/-21) microg, respectively. Mean daily Se
      intake (from all sources) was significantly higher in men of all ages than women
      of all ages at levels of 60 and 44 microg, respectively (P<0.001). Meat/meat
      products (30%), bread and rolls (24%), fish/fish products (approximately 11%),
      and milk and yoghurt (9%) were the main contributors to mean daily Se intake.
      Adequacy of Se intake in population groups was estimated as the percentage of the
      population with mean daily Se intakes that were lower than the average
      requirement of 40 microg. Using this measure, 45.6% of women and 17.1% of men had
      inadequate Se intakes. CONCLUSION: A significant prevalence of inadequate Se
      intakes was observed in Irish adults. Therefore, it would seem prudent that the
      Se status of the Irish population be investigated at this time.

PMID- 12001011
TI  - Dietary magnesium intake in type 2 diabetes.
AB  - BACKGROUND: Magnesium deficiency is common in type 2 diabetes and may have a
      negative impact on glucose homeostasis and insulin resistance, as well as on the
      evolution of complications such as retinopathy, thrombosis and hypertension.
      OBJECTIVE: To assess the dietary magnesium intake of patients with type 2
      diabetes in Zurich, Switzerland and to compare the magnesium intake of diabetic
      and non-diabetic subjects. DESIGN: The magnesium intake of 97 randomly selected
      patients with type 2 diabetes and 100 healthy, non-diabetic controls matched for
      age and sex was estimated using a diet history method. During winter and summer
      periods, mean daily magnesium intakes were calculated from detailed information
      given by the test subjects about their eating habits over the previous 2 months.
      The calculations were performed using EBIS, a computer program based on a German
      nutrient data base (BLS 2.3), with food items specific to Switzerland added or
      directly analysed when necessary. RESULTS: The mean+/-s.d. daily magnesium intake
      of the male diabetic and male control subjects was 423.2+/-103.1 and 421.1+/
      111.0 mg, respectively. The mean daily magnesium intake of the female diabetic
      and female control subjects was 419.1+/-109.7 and 383.5+/-109.7 mg, respectively.
      There were no significant differences in daily magnesium intake between the
      diabetic and the non-diabetic subjects and mean intakes in both groups exceeded
      Swiss recommended dietary intakes. CONCLUSIONS: Dietary intake of magnesium
      appears sufficient in Swiss adults with type 2 diabetes and is unlikely to
      contribute to the aetiology of magnesium deficiency. SPONSORSHIP: The Swiss
      Federal Institute of Technology, Zurich, Switzerland.

PMID- 12001012
TI  - HIV status and sociodemographic correlates of maternal body size and wasting
      during pregnancy.
AB  - OBJECTIVE: To examine HIV status and sociodemographic variables as correlates of
      body size (height, body mass index (BMI), and mid-upper-arm circumference (MUAC))
      and wasting (MUAC <22 cm) in pregnant women. DESIGN: Cross-sectional study.
      SETTING: Four antenatal clinics in Dar es Salaam, Tanzania. SUBJECTS: Women
      presenting for first prenatal visit before the 23rd week of gestation, between
      April 1995 and July 1997 (n=13 760). RESULTS: Mean MUAC, BMI and height were 25.5
      cm, 23.5 kg/m(2) and 155.1 cm, respectively. The prevalence of HIV infection was
      13.1% and the overall prevalence of wasting was 4.7%. Wasting was 34% (95% CI=3%,
      73%) more prevalent among HIV-infected than in uninfected mothers, after
      adjusting for week of gestation, height and sociodemographic indicators. The risk
      of wasting associated with HIV infection was highest among women with low level
      of education or unable to contribute to the household income. From a multiple
      linear regression model, BMI was positively associated with mother's age, level
      of education and money spent on food, but not with HIV infection, after adjusting
      for week of gestation. In multivariate analysis, height increased monotonically
      by categories of maternal age and level of education, and was also positively
      correlated with the ability to contribute to household income, the amount of
      money spent on food per person per day, and having a professional partner.
      CONCLUSION: HIV infection is a significant risk factor for wasting among pregnant
      women, particularly in groups of low socioeconomic status (SES). SES indicators
      are strongly correlated with maternal height and with BMI during the first and
      second trimesters of pregnancy independently of HIV status. SPONSORSHIP: The
      National Institute of Child Health and Human Development (NICHD R01 32257), and
      the Fogarty International Center (NIH D43 TW00004).

PMID- 12001013
TI  - Estimation of carotenoid accessibility from carrots determined by an in vitro
      digestion method.
AB  - OBJECTIVE: To develop an in vitro digestion method to assess the impact of heat
      treatment, particle size and presence of oil on the accessibility (available for
      absorption) of alpha- and beta-carotene in carrots. DESIGN: Raw and cooked
      carrots were either homogenized or cut into pieces similar to chewed items in
      size. The carrot samples, with or without added cooking oil, were exposed to an
      in vitro digestion procedure. Adding a pepsin-HCl solution at pH 2.0 simulated
      the gastric phase. In the subsequent intestinal phase, pH was adjusted to 7.5 and
      a pancreatin-bile extract mixture was added. Carotenoids released from the carrot
      matrix during the digestion were extracted and quantified on high-performance
      liquid chromatography (HPLC). RESULTS: Three percent of the total beta-carotene
      content was released from raw carrots in pieces. When homogenized (pulped) 21%
      was released. Cooking the pulp increased the accessibility to 27%. Addition of
      cooking oil to the cooked pulp further increased the released amount to 39%. The
      trends for alpha-carotene were similar to those for beta-carotene. CONCLUSION:
      The described in vitro digestion method allows a rapid estimation of carotene
      accessibility in processed carrots, which may reliably predict in vivo behavior.
      SPONSORSHIP: This study was supported by the Swedish International Development
      Cooperation Agency (SIDA) and the International Program in the Chemical Sciences
      (IPICS), Uppsala University, Sweden.

PMID- 12001014
TI  - The effect of conventional vitamin D(2) supplementation on serum 25(OH)D
      concentration is weak among peripubertal Finnish girls: a 3-y prospective study.
AB  - OBJECTIVES: To study the effect of vitamin D supplementation and the impact of
      summer season on serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish 9-15-y-old
      girls. DESIGN: Three-year follow-up study with vitamin D(2) supplementation using
      D(2) 10 microg daily from October to January for the first and from October to
      February for the second winter as well as 20 microg daily from October to March
      for the third winter. SETTING: Paavo Nurmi Centre, University of Turku, Turku,
      Finland. SUBJECTS: A total of 171 female volunteers aged 9-15 y. METHODS: Vitamin
      D and calcium intakes were estimated by a semi-quantitative food frequency
      questionnaire (FFQ). S-25(OH)D was measured by radioimmunoassay. RESULTS: The
      median daily dietary intakes of vitamin D and calcium were 3.8 microg
      (interquartile range (IQR) 2.7-5.0) and 1451 mg (IQR 1196-1812), respectively,
      over 3 y. The prevalence of severe hypovitaminosis D (S-25(OH)D<20 nmol/l) was
      14% and of moderate hypovitaminosis D (20 nmol/l < or = S-25(OH)D < or = 37.5
      nmol/l) 75% at baseline in winter. None of the participants had severe
      hypovitaminosis D in summer. The effect of 10 microg of D(2) daily was
      insufficient to raise S-25(OH)D from baseline. The daily supplementation of 20
      microg of D(2) increased S-25(OH)D significantly in wintertime compared with the
      non-supplement users (to 45.5 vs 31.8 nmol/l; P<0.001). None of the subjects with
      vitamin D(2) supplementation approximately 20 microg daily had severe
      hypovitaminosis D; however, 38% of those participants had moderate
      hypovitaminosis D at 36 months. Sun exposure in summer raised mean S-25(OH)D to
      62.0 nmol/l. Both the daily supplementation of approximately 20 microg of D(2)
      and summer sunlight exposure had more effect on those who had severe
      hypovitaminosis than those who had a normal vitamin D status (increase of 24.2 vs
      0.9 nmol/l (P<0.001), and 38.8 vs 18.2 nmol/l (P<0.001), respectively).
      CONCLUSION: Vitamin D supplementation daily with 20 microg is needed to prevent
      hypovitaminosis D in peripubertal Finnish girls in winter. Sunlight exposure in
      summer is more effective than approximately 20 microg of D(2) supplementation
      daily in winter to raise S-25(OH)D. Both the daily supplementation with 20 microg
      of D(2) and summertime sunlight exposure had more effect on those who had severe
      hypovitaminosis D than those who had a normal vitamin D status. SPONSORSHIP:
      Supported by the Yrjo Jahnsson Foundation and the Medical Research Foundation of
      the Turku University Central Hospital.

PMID- 12001015
TI  - Knowledge, attitude and practice of health workers in Keffi local government
      hospitals regarding Baby-Friendly Hospital Initiative (BFHI) practices.
AB  - OBJECTIVE: To assess the knowledge, attitude and practice of health workers
      towards Baby Friendly Hospital Initiative (BFHI) practices and thereafter plan an
      advocacy on BFHI training of the workers. DESIGN: A randomised cross-sectional
      study. SETING: Ten out of 16 health facilities reflecting all the levels of
      healthcare provision in Keffi Local Government Area in Nassarawa State, Nigeria,
      were selected. Staff of these health facilities had not received BFHI training,
      although breastfeeding is the norm in this population, exclusive breastfeeding is
      almost zero. SUBJECTS: A total of 250 health workers (six doctors, 160 nurses and
      84 auxiliary staff) met in the health facilities at the time of interview.
      INTERVENTION: A structured questionnaire based on 10 steps to successful
      breastfeeding was administered by one of the authors and a Lactad nurse between
      July and October 1995. RESULTS: Fifty-two (20.8%) were aware of the need for
      initiating breastfeeding within 30 min of birth and 92 (36.8%) were aware of
      breastfeeding support groups. However, there were significant differences in the
      level of awareness among the doctors compared to the other categories of health
      staff (P<0.05). Also, 48 (19.2%) of the health workers believed that babies less
      than 6 months of age should not be given water (statistical difference (P<0.05)
      between doctors' attitude and that of the other health workers). Thirteen (5.22%)
      health workers could demonstrate correct positioning and attachment. CONCLUSION:
      There was general lack of awareness of some major recommended practices in the
      hospitals that will promote and sustain breastfeeding. There is therefore the
      need for policy changes and BFHI training for the staff of these health
      facilities to respond to the concern and growing need for proper infant/young
      child feeding.

PMID- 12001016
TI  - Magnesium bioavailability from mineral water. A study in adult men.
AB  - OBJECTIVE: To assess magnesium enteral absorption from a magnesium-rich mineral
      water. DESIGN: Experimental study. SETTING: Department of Nuclear Medicine,
      Brugmann Hospital, Brussels, Belgium. SUBJECTS: Ten healthy male volunteers in
      the age range 25-42 y. INTERVENTION: Each subject completed two sessions in a
      random order. At one session, they received an oral load of 300 ml of water
      (containing 1.2 mmol Mg), traced with (28)Mg, and at the other session they
      received an intravenous injection of (28)Mg, in order to take into account the
      metabolism of endogenous magnesium. The dietary consumption was further noted on
      a weekly diary. RESULTS: The mean bioavailability was 59.1% (s.d.+/-13.6).
      Magnesium absorption and age were significantly inversely correlated (r=-0.68,
      P=0.035). CONCLUSION: Magnesium-rich mineral water is a reliable source of
      magnesium. Our observation of decreased magnesium absorption with age deserves
      further investigations. SPONSORSHIP: The study was sponsored by SEV, Bourg la
      Reine, France.

PMID- 12001017
TI  - Factors affecting the introduction of complementary foods in the preterm infant.
AB  - OBJECTIVES: The aim of the study was to identify current infant feeding practices
      among carers of preterm infants. DESIGN: Structured interviews on milk and
      complementary feeding practices were conducted with mothers of preterm infants at
      intervals until infants were 12 months corrected age. SETTING: Recruitment took
      place in three local Surrey hospitals over a 2 y period. SUBJECTS: Two-hundred
      and fifty-three preterm infants (139 male, 114 female) including 33 sets of twins
      and three sets of triplets were recruited. RESULTS: Forty-nine percent of the
      preterm infant group received first solid foods (the commencement of 'weaning')
      before the current Department of Health (DoH) guideline. The mean+/-s.e.m.
      weaning age from birth was 17.1+/-0.23 weeks. Ninety-five percent of the infants
      were weaned before the DoH guideline when the data was examined from term (mean
      11.5+/-s.e.m. 0.21 weeks). Twenty-one percent were weaned before the DoH
      guideline for preterm infants which is that 'the infant weighs at least 5 kg'
      (mean 5.61+/-s.e.m. 0.01 kg). Human milk-fed infants were significantly lighter
      at weaning than combined milk-fed infants (5.32+/-0.12 vs 5.72+/-0.01 kg; P<0.05)
      even though they were weaned at a similar age. Infant formula-fed infants (mean
      weaning age from term 10.2+/-0.47 weeks) were weaned significantly earlier than
      both human milk-fed (11.9+/-0.49 weeks; P<0.05) and combined milk-fed (11.9+/
      0.25 weeks; P<0.005) infants. CONCLUSIONS: The introduction of complementary
      foods varied widely between carers of preterm infants and compliance with DoH
      guidelines was poor. Further studies on preterm infants are necessary to see if
      weaning practices affect long-term growth and morbidity and to provide a basis
      for the development of appropriate recommendations. SPONSORSHIP: This work was
      funded by the MAFF Food Intolerance Programme.

PMID- 12001018
TI  - The impact on eating habits of temporary translocation from a Mediterranean to a
      Northern European environment.
AB  - OBJECTIVE: To assess the effect of temporary translocation from a Mediterranean
      to a Northern European environment on the eating habits of a group of foreign
      students. DESIGN: Cross-sectional survey of eating habits before and after moving
      from Greece to Glasgow, Scotland. SETTING: University of Glasgow. SUBJECTS:
      Eighty post-graduate Greek students. INTERVENTIONS: A self-administered
      questionnaire comprising of three major sections: (1) general eating habits; (2)
      frequency of eating selected food items; (3) opinion of food availability in
      Glasgow. RESULTS: After moving to Glasgow, significant decreases were reported in
      the frequency of consuming fresh fruit, raw vegetables, fish, legumes, meat,
      poultry and fresh fruit juice. The frequency of eating biscuits, savoury snacks,
      soft/fizzy drinks, alcoholic drinks and mayonnaise, dips and sauces increased.
      The estimated median daily consumption of fruit and vegetables decreased from 363
      g in Greece to just 124 g in Glasgow, well below the Scottish and WHO dietary
      target of 400 g/day. The main perceived barriers to maintaining customary eating
      habits were the price of food, the lack of familiar tastes, the greater
      availability of convenience food and the limited variety of food available in
      Glasgow, when compared to Greece. CONCLUSIONS: These findings highlight the
      difficulties that migrant populations face in retaining traditional, often
      healthier, eating habits when migrating to a foreign country. Barriers of high
      cost, limited availability and poor quality of familiar foods, need to be
      addressed in order for migrants to maintain their customary eating patterns.
      Furthermore, these barriers need to be addressed before nutritionists can expect
      to see the widespread adoption of the Mediterranean diet by Western populations
      less familiar with this eating pattern.

PMID- 12001019
TI  - Dark adaptation pattern of pregnant women as an indicator of functional
      disturbance at acceptable serum vitamin A levels.
AB  - BACKGROUND: As a result of lack of precise guidelines, nutritional surveys on
      adults and high-risk groups are using diverse reference values as a dividing line
      between normal and deficient vitamin A status. OBJECTIVE: To investigate whether
      pregnant women at marginally normal serum retinol status exhibit functional
      alteration that are characteristic of a deficiency state. SETTING: Antenatal
      clinic, Gondar teaching hospital. SUBJECTS: Ninety-six healthy pregnant women
      were recruited for the study at the antenatal clinic. INTERVENTION: The dark
      adaptation time was tested in 48 pregnant women with marginal serum retinol
      level. The time lapse to see successive light stimuli of diminishing luminescence
      grade and change in retinal sensitivity pattern was measured using dark
      adaptometer. Results were compared with the results of a control group of women
      of similar age, parity and gestational period but with serum retinol values above
      35 microg/dl. RESULTS: The mean serum retinol levels of cases and controls were
      23.35 microg/dl and 40.47 microg/dl respectively (P<0.008). Cases have a lower
      dark adaptation than their controls, shown by their remarkably reduced
      sensitivity to light. For instance at mean final light threshold was -2.20+/-0.11
      log cd/m(2) in cases as compared to -2.88+/-0.1 log cd/m(2) in the normal group
      (P<0.001). CONCLUSION: During pregnancy, dark adaptation was strongly associated
      with serum retinol concentration and women with marginal vitamin A concentration
      had lower dark adaptation. Hence marginally normal serum retinol levels should be
      categorized as a deficiency state, at least in pregnant women.

PMID- 12001020
TI  - Dietary iodine sources other than fish.

PMID- 12001021
TI  - [The assessment of subjective distress related to hyperacusis with a self-rating
      questionnaire on hypersensitivity to sound].
AB  - BACKGROUND: So far there has been no adequate measure to assess or illustrate, in
      terms of different levels, subjective distress related to hypersensitivity to
      sound. METHOD AND PATIENTS: The here presented work describes and discusses the
      construction of a questionnaire to assess subjective distress related to
      hypersensitivity to sound (GUF). Between May and September 2000 226 patients that
      experienced suffering from hypersensitivity to sound as well as from chronic
      tinnitus, completed a first version of the questionnaire on admittance to the
      hospital. Of these patients 27.9 % were out-patients and 72.1 % were in-patients.
      In addition, the in-patients completed the questionnaire again during their last
      week of treatment. The 27 items of the GUF were interpreted by factor analysis to
      explore and determine the structure of the questionnaire; the number of items was
      reduced under the aspects of consistency and reliability. Finally, the revised
      version of the GUF underwent a first validation. RESULTS: The factor analysis
      shows three factors explaining 50.65 % variance (factor 1 [KRH], cognitive
      reactions to hyperacusis; factor 2 [ASV], actional/somatic behaviour; factor 3
      [ERG], emotional reaction to external noises). First attempts to validate the
      questionnaire are promising; it appears that the GUF is also sensitive to therapy
      effects. CONCLUSIONS: The here presented questionnaire is suitable for
      identifying distinct levels of subjective distress related to hypersensitivity to
      sound. Thus, for the first time, there is an adequate measure for assessment
      available. Furthermore, results of part of the sample show that the GUF is also
      suitable for therapy evaluation.

PMID- 12001022
TI  - [Follow-up assessment of intratympanic gentamicin therapy and Saccotomia in
      Meniere's Disease].
AB  - BACKGROUND: The intratympanic application of ototoxic antibiotics and saccotomia
      have been well documented in severe cases of one-sided Meniere's disease for 30
      years now. Both treatment methods are still subject to controversial discussion.
      PATIENTS AND MATERIAL: This study includes 8 patients suffering from persistent
      one-sided Meniere's disease after treatment with gentamicin application and
      additional saccotomia (n=2). We performed follow-up visits including the
      assessment of hearing ability, vestibular function and cranial MRI, 2-10 years
      after onset of treatment. RESULTS: After therapeutic interventions 7 patients
      reported to be healed of their symptom vertigo. In 4 patients the gentamicin
      treated vestibular organ did not respond to thermic stimulus at the time of
      follow-up examination. Auditory threshold shift was observed in 3 patients (1
      permanent, 2 temporary), whereas hearing threshold improved in 2 patients.
      Tinnitus was attenuated in 3 patients, while 1 patient suffered from
      posttherapeutic onset of tinnitus. Morphological and structural changes due to
      Meniere's disease and treatment procedures were ruled out by cranial MRI.
      CONCLUSION: The intratympanic application of ototoxic medication is a safe and
      effective treatment method in severe cases of Meniere's disease. Saccotomia
      should be considered as therapeutic regimen for persistent symptoms after
      repeated application of gentamicin.

PMID- 12001023
TI  - [Prognostic value of antibodies against p53 in patients with oral squamous cell
      carcinoma--five years survival rate].
AB  - BACKGROUND: p53 gene aberrations are the most common genetic changes seen in
      human carcinogenesis. Frequently, single point mutations are detected, resulting
      in increased levels of (an aberrant) p53 protein in tumor cells. The cellular
      protein produced appears to become immunogenic during tumor development, inducing
      the production of circulating antibodies against p53. METHODS: For this study,
      sera from 126 patients with oral squamous cell carcinomas (102 primary tumours
      and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and
      their further clinical course was followed up for more than 5 years. 80 sera from
      internal medicine patients without known or suspected neoplasm served as control.
      A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova,
      Hamburg was used to detect p53 autoantibodies. RESULTS: In 18.6 % of the patients
      with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and
      also in 50 % of the patients with recurrent or local secondary carcinomas. None
      of the sera of the control group was positive. Patients with anti-p53 have
      noticeably poorer prognosis (Log Rank Test, p < 0.005). After a period of 5
      years, the overall survival rate of the p53-positive group was 24 % - less than
      half of that of the p53-negative group with a survival rate of 51 %. CONCLUSIONS:
      : The detection of p53 autoantibodies definitely permits a clearer prognostic
      assessment, which in turn influences clinical procedures. If p53 autoantibodies
      are detected in a patient during therapy, the applied therapeutic method should
      be reconsidered and the patient be more closely observed than other, p53 negative
      patients.

PMID- 12001024
TI  - [Clinical experience with power-regulated contact laser surgery for the paranasal
      sinuses and the anterior skull base].
AB  - BACKGROUND: While laser surgical methods in Otorhinolaryngology have become
      widely established, their use in revision surgery for chronic-polypous sinusitis
      has been regarded as hazardous due to the vicinity of the anterior skull base and
      the orbit. However, new experience with laser-tissue interaction in contact
      irradiation together with effective power feedback control mechanisms require a
      re-evaluation of laser revision surgery in this field. PATIENTS AND METHODS:
      After 742 primary, endonasal-microscopic sinus surgery procedures, 86 patients
      had 128 Nd:YAG-laser sessions performed within an interval of 1 - 24 months after
      primary surgery for recurrent polyposis, which had been irresponsive to
      medication. The maximum power delivered was 10 to 20 W. RESULTS: Recurrent
      polyposis appeared mostly in the maxillo-ethmoid angle, followed by the maxillary
      sinus roof and the maxillary sinus bottom. In 63 of 86 patients, no further
      polyposis was seen after laser surgery. If more than one laser session had to be
      performed, recurrent polyposis appeared in a different region in most cases.
      Those areas lasered first showed a reduced tendency to recurrence. There was
      moderate bleeding during laser surgery in 6 cases with reduced visibility, but no
      other serious complications were recorded. CONCLUSIONS: Laser surgery for chronic
      polypous sinusitis is an alternative to conventional revision surgery, if medical
      treatment fails and recurrent polyposis is confined to certain regions. Feedback
      controlled contact laser power delivery adds further therapeutic safety when
      applied next to the anterior skull base and the orbit.

PMID- 12001025
TI  - [Poly-beta-hydroxybutyric acid (PHB) films and plates in defect covering of the
      osseus skull in a rabbit model].
AB  - BACKGROUND: Titan plates have proven a success in the operative assistance of
      middle face fractures for stabile osteosynthesis. Also bioresorbant materials are
      being used increasingly. METHOD: Films and plates made from poly-beta
      hydroxybutyric acid (PHB) with two holes and bolts are tested subperiostally on
      the osseus skull of 15 rabbits or respectively on cut trough zygomatic arches.
      The test bodies and the surrounding tissue are explantated after a defined period
      and are clinically and histologically prepared. RESULTS: All implants healed
      well. There were no macroscopic or microscopic signs of inflammation. A very
      slow, clinically not recordable decomposition followed. A "leap" in the
      decomposition evidently took place between the 20th and 25th month. Only initial
      signs of resorbation were to be found microfocally on the surface of the implant
      until 20 months after implantation but no more test body could be detected after
      25 months. CONCLUSION: PHB is suitable for defect covery of the osseus skull or
      respectively as osteosynthesis material for fractures of the visceral cranium.

PMID- 12001026
TI  - [Otorhinolaryngology, head and neck surgery in Kenya--consequences of demographic
      parameters].
AB  - BACKGROUND: In the time of evidence based medicine the analysis of the influence
      of demographic parameters and different environmental factors on the treatment
      concepts in a country is often neglected. This is also true for
      Otorhinolaryngology. METHOD: An evaluation of the situation concerning
      distribution of physicians, diagnostic procedures and epidemiology in Kenya has
      been performed. These factors are discussed in consideration of their effect on
      the incidence of different diseases and their treatment under the specific socio
      economic conditions for the otolaryngological situation in Kenya. RESULTS: In
      Kenya 28 otolaryngologists are registered that concentrate on few urban regions.
      Chronic otitis media, malignant tumors in the head and neck region and AIDS
      associated diseases have meanwhile increased dramatically. Numerous instruments
      and equipment for diagnosis are missing. Bigger equipment for CT scans are nearly
      exclusively used by private hospitals. PERSPECTIVE: Beside a better provision
      with different equipment for diagnosis it is especially the organization of
      certain training programmes where local physicians are further educated that may
      lead to an optimised medical care in Kenya.

PMID- 12001027
TI  - [Comments on the removal of the parotid gland due to erroneous diagnosis of
      Sjogren's syndrome].

PMID- 12001028
TI  - [Radical-induced cellular injury and the antioxidative glutathion defence system
      of the cochlea].

PMID- 12001029
TI  - Introduction: the importance of identifying and treating complications of human
      immunodeficiency virus disease.

PMID- 12001030
TI  - Biology of anemia, differential diagnosis, and treatment options in human
      immunodeficiency virus infection.
AB  - Anemia is the most common hematologic manifestation of human immunodeficiency
      virus (HIV) infection and acquired immunodeficiency syndrome. The causes of HIV
      related anemia are multifactorial and include direct and indirect effects of HIV
      infection. HIV-related anemia generally is due to reduced red blood cell (RBC)
      production, secondary to a variety of causes, but it may also involve nutritional
      deficiencies, increased RBC destruction, or a combination of these problems.
      Evaluation of hemoglobin level, reticulocyte count, bilirubin, and mean
      corpuscular volume value and review of the peripheral blood smear are necessary
      for diagnosis. Treatment of HIV-related anemia should address the correctable
      underlying causes of this disorder, such as modifications of offending
      medications, nutritional deficiencies, and parvovirus infection. Patients with
      HIV infection have a blunted erythropoietin response to anemia. Therapeutic
      modalities for anemia that is not amenable to correction include blood
      transfusion and recombinant human erythropoietin (epoetin alfa).

PMID- 12001031
TI  - The impact of anemia on quality of life in human immunodeficiency virus-infected
      patients.
AB  - Anemia is the most commonly encountered hematologic abnormality in human
      immunodeficiency virus (HIV)-positive patients, occurring with increasing
      frequency as the disease progresses. Several factors play a role in the
      development of anemia in patients with HIV, including chronic disease,
      opportunistic infections, and certain nutritional deficiencies. Despite the high
      prevalence of anemia in this population, the symptoms of anemia are frequently
      overlooked, although anemia can significantly affect a patient's ability to carry
      on even normal activities of daily living. Therefore, approaches--including the
      treatment of causative infections, discontinuation of certain drugs, or use of
      recombinant human erythropoietin (epoetin alfa)--aimed at increasing hemoglobin
      levels to normal or near-normal levels would be expected to improve quality of
      life (QOL). The purpose of this article is to describe the effects of anemia on
      QOL and to provide an overview of several studies showing that QOL improves with
      the alleviation of anemia.

PMID- 12001032
TI  - Immune therapy: non-highly active antiretroviral therapy management of human
      immunodeficiency virus-infected patients.
AB  - The complexity of human immunodeficiency virus (HIV) immunopathogenesis has
      prompted multiple strategic approaches to re-establish normal immune responses.
      Highly active antiretroviral therapy (HAART) can control viral replication, but
      it is unable to restore HIV-specific immunity. Newer approaches for managing HIV
      infection are focusing on cell-mediated immune responses, including the potential
      for improved immunologic control over HIV replication. Cytokines, such as
      interleukin (IL)-2 and IL-12, are being evaluated for their ability to enhance
      cell-mediated immunity, which is thought to be critical for immunologic control.
      Initial studies with IL-2 have demonstrated an improvement in CD4 cell counts,
      and large randomized trials are underway to determine the long-term clinical
      efficacy of IL-2 in combination with antiretroviral therapy, including HAART.
      Stimulating the immune response against HIV by use of exogenous (therapeutic
      vaccination) or endogenous (structured treatment interruption) antigens with or
      without immune adjuvants or cytokines, such as IL-2, is another approach
      currently being explored.

PMID- 12001033
TI  - Selected metabolic and morphologic complications associated with highly active
      antiretroviral therapy.
AB  - Metabolic and morphologic changes have been described in patients with human
      immunodeficiency virus (HIV) infection. In the short term, these disorders can be
      debilitating and may require medical intervention, including alterations in
      antiretroviral therapy regimens. The long-term consequences have not been fully
      realized, but are important, particularly in the era of durable HIV disease
      management with highly active antiretroviral therapy. This review focuses on 3 of
      the important morphologic or metabolic changes, namely alterations in body fat
      distribution, dyslipidemia, and lactic acidosis. The prevalence of each of these
      disorders remains unknown due to varied definitions and difficulty in recognition
      of the conditions for both the patient and the clinician. Treatment regimens
      directed at these abnormalities are being developed, but clinical trials are
      needed to fully ascertain the efficacy and safety of such interventions.

PMID- 12001034
TI  - Treatment of hepatitis C and anemia in human immunodeficiency virus-infected
      patients.
AB  - Because of shared modes of transmission, co-infection with human immunodeficiency
      virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV
      increases HCV virus load, liver-related mortality, and the risk of sexual and
      perinatal transmission of HCV, and it may accelerate HCV disease progression.
      With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha
      2b/ribavirin therapy, long-term remission is possible for HCV-infected patients.
      Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can
      achieve similar response rates in HCV/HIV-co-infected individuals with no adverse
      effect on HIV RNA concentrations. Although adverse effects are more frequent with
      combination therapy than with IFN-alpha monotherapy, most are manageable. In
      addition, few instances of drug-drug antagonism have been reported among drugs
      used to treat each disease, although further study is necessary. Ribavirin
      associated hemolytic anemia is a potential problem in a patient population that
      is already susceptible to anemia but is manageable with recombinant human
      erythropoietin (epoetin alfa).

PMID- 12001035
TI  - Associations of anemia, treatments for anemia, and survival in patients with
      human immunodeficiency virus infection.
AB  - Three large observational cohort studies suggest that, after controlling for
      virus load and CD4 cell count, anemia is related to disease progression and
      survival in patients with human immunodeficiency virus (HIV) infection. Recovery
      from anemia has been linked to improved survival outcomes. Blood transfusion has
      been associated with accelerated disease progression and mortality in patients
      with HIV infection, and review of related literature suggests that the mechanism
      for negative transfusion-associated outcomes may be transfusion-related
      immunosuppression. Therefore, the use of transfusion should be restricted to
      patients with acute or severe anemia. Prescription of epoetin alfa has been
      associated with increased survival in an observational cohort among patients with
      HIV infection and anemia. In the absence of data from a clinical trial
      documenting the effect of treating anemia on survival, clinicians should consider
      non-transfusion options for management of anemia on the basis of clinical status
      and patient functional ability.

PMID- 12001036
TI  - Adherence to antiretroviral therapy by human immunodeficiency virus-infected
      patients.
AB  - Poor adherence to antiretroviral treatment regimens has serious consequences for
      human immunodeficiency virus-infected patients, including failure to prevent
      viral replication and an increased risk of developing viral resistance. Recent
      data suggest that the level of medication adherence required for optimal
      treatment effectiveness is extremely high. Treatment adherence can be measured by
      use of a variety of methods, including patients' self-reports, pharmacy-based
      approaches, pill counts, and electronic monitoring. However, these measures of
      adherence have different strengths and weaknesses in regard to practical
      application and identifying deficient adherence. All patients receiving
      antiretroviral therapy require support to insure a high level of treatment
      adherence, but the evidence about effective interventions is limited. Emerging
      evidence suggests adherence interventions should employ a multidisciplinary
      effort involving health care providers, social support networks, family, and
      friends. Although such programs will require a substantial investment in terms of
      time and energy, the rewards associated with optimal treatment adherence are
      worth the effort.

PMID- 12001037
TI  - Differing influences of virus burden and immune activation on disease severity in
      secondary dengue-3 virus infections.
AB  - Dengue hemorrhagic fever (DHF), the most severe form of illness following
      infection with a dengue virus, is characterized by plasma leakage,
      thrombocytopenia, and hepatic inflammation. The interrelationships among virus
      burden, immune activation, and development of DHF were examined in 54 children
      with secondary dengue-3 virus infections participating in a prospective, hospital
      based study. DHF was associated with higher mean plasma viremia early in illness
      and earlier peak plasma interferon-gamma levels. Maximum plasma viremia levels
      correlated with the degree of plasma leakage and thrombocytopenia. Maximum plasma
      levels of interleukin (IL)-10 and soluble tumor necrosis factor receptor-II
      correlated with the degree of thrombocytopenia, independently of viremia levels.
      Hepatic transaminase elevation correlated with plasma soluble IL-2 receptor
      levels and not with viremia levels. Quantitative differences in virus burden and
      host immune responses, and the timing of type 1 cytokine responses, have
      differing influences on the severity of disease manifestations during secondary
      dengue-3 virus infections.

PMID- 12001038
TI  - A randomized, double-blind, placebo-controlled trial of dexamethasone in severe
      respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical
      outcome.
AB  - Forty-one previously healthy children <2 years of age who required mechanical
      ventilation for respiratory syncytial virus (RSV) infection were randomized to
      receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously
      every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in
      fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0,
      1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling
      demonstrated a significantly greater decline in mean tracheal RSV quantity in the
      placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21
      log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No
      differences were found between groups in nasal RSV quantity, white blood cell
      counts in tracheal or nasal aspirates, serum neutralizing antibody titers during
      convalescence, or duration of mechanical ventilation, intensive care unit stay,
      or hospital stay.

PMID- 12001039
TI  - Increased risk of high-grade anal neoplasia associated with a human
      papillomavirus type 16 E6 sequence variant.
AB  - Expression of the E6 and E7 genes of human papillomavirus (HPV) type 16 have been
      implicated in the etiology of anogenital premalignant and malignant lesions. To
      evaluate whether variations in the HPV-16 E6 sequence were related to the
      incidence of high-grade anal neoplasia, 628 HPV-16-positive anal specimens from
      193 human immunodeficiency virus (HIV)-positive and 59 HIV-negative participants
      were typed for variations in 15 E6 nucleotide positions. Although most
      participants were infected with a prototype strain, 15 (6%) carried the G131
      variant, and 12 (5%) were infected with the Af1a variant. Two new variants not
      previously reported were identified as well. An elevated risk for high-grade anal
      squamous intraepithelial lesions was associated with infection by G131 variants,
      compared with the prototype strain (odds ratio, 3.4; 95% confidence interval, 1.1
      10), after controlling for HIV status. These data provide further evidence for
      HPV strain variation as a factor in determining the natural history of anogenital
      neoplasia.

PMID- 12001040
TI  - Reactivation of and primary infection with human herpesvirus 8 among solid-organ
      transplant recipients.
AB  - Human herpesvirus 8 (HHV-8) is the causal agent of all forms of Kaposi's sarcoma,
      including the iatrogenic form that presents in solid-organ transplant recipients.
      A longitudinal study of HHV-8 seropositivity was conducted among a cohort
      consisting of children and adult solid-organ transplant recipients. Antibodies to
      HHV-8 lytic proteins were detected by an indirect immunofluorescence assay in
      serum samples of 100 transplant recipients. HHV-8 seropositivity increased
      significantly, from 5.3% before transplantation to 15.8% after transplantation
      (P<.01). Seropositivity was not related to the age of the patient or the type of
      organ transplanted. HHV-8 seroconversion occurred in both children and adult
      recipients. None of the seroconversion events was related to the source of the
      donor organ. These findings suggest that HHV-8 infection is not uncommon among
      both adult and children transplant recipients and that viral infection may be
      acquired from an outside source other than the transplanted organ.

PMID- 12001041
TI  - Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on
      disease progression in a large cohort of HIV-1-positive persons in Uganda.
AB  - The effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D
      on disease progression was investigated in 1045 adults in Uganda. At enrollment
      and every 6 months, a clinical history, examination, and laboratory
      investigations that included CD4 cell counts were done. HIV-1 envelope subtype
      was assessed mainly by peptide serology supplemented by heteroduplex mobility
      assay and DNA sequencing. A multivariate analysis of survival was performed to
      assess the prognostic value of HIV-1 subtype on death. A marginal general linear
      model also determined the effect of subtype on CD4 cell count during follow-up.
      Subtype D was associated with faster progression to death (relative risk, 1.29;
      95% confidence interval, 1.07-1.56; P=.009) and with a lower CD4 cell count
      during follow-up (P=.001), compared with subtype A, after adjusting for CD4 cell
      count at enrollment. In Africa, envelope subtype D is associated with faster
      disease progression, compared with subtype A.

PMID- 12001042
TI  - A randomized trial of simplified maintenance therapy with abacavir, lamivudine,
      and zidovudine in human immunodeficiency virus infection.
AB  - This randomized study evaluated the efficacy and tolerability of continued
      treatment with protease inhibitor plus nucleoside-analogue combination regimens
      (n=79) or a change to the simplified regimen of abacavir-lamivudine-zidovudine
      (n=84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1)
      RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation.
      After a median follow-up of 84 weeks, virologic failure was 6% in the
      continuation and 15% in the simplified group (P=.081). Previous zidovudine
      monotherapy or dual therapy and archived reverse transcriptase resistance
      mutations in HIV-1 DNA at baseline were significant predictors of failure. Study
      treatment was discontinued because of adverse events in 20% of the continuation
      and 7% of the simplified group (P=.021). Simplification to abacavir-lamivudine
      zidovudine significantly decreased nonfasting cholesterol and triglyceride
      levels; however, this switch strategy carries a risk of virologic failure when
      treatment history or resistance testing suggest the presence of archived
      resistance mutations to the simplified regimen.

PMID- 12001043
TI  - Low risk of treatment failure after substitution of nevirapine for protease
      inhibitors among human immunodeficiency virus-infected patients with virus
      suppression.
AB  - There is little information about the risk of treatment failure after a switch
      from human immunodeficiency virus (HIV) protease inhibitors (PIs) to nevirapine
      (Nvp) for patients with successful virus suppression. This study compared the 1
      year risk of treatment failure for patients switching from a first PI-containing
      antiretroviral regimen to Nvp (Nvp group) with the risk for patients switching to
      second-line PIs (PI group) in the ATHENA (AIDS Therapy Evaluation, The
      Netherlands) study cohort (n=2470) whose HIV-1 RNA loads were < or = 500
      copies/mL. Treatment failure was defined as measurement of HIV-1 RNA loads >500
      twice or >10,000 copies/mL once or discontinuation of treatment for any reason.
      There were 446 eligible patients, 125 in the Nvp group and 321 in the PI group.
      The risk of treatment failure in the Nvp group, after data were adjusted for
      other risk factors, was 5-fold (95% confidence interval, 0.1-0.4) lower than the
      risk in the PI group, primarily because the discontinuation rate was lower. In
      patients with virus suppression, a switch to Nvp is more likely than a switch to
      second-line PIs to result in sustained virus suppression and maintenance of the
      new regimen.

PMID- 12001044
TI  - A comprehensive study of Candida-specific antibodies in the saliva of human
      immunodeficiency virus-positive individuals with oropharyngeal candidiasis.
AB  - Oropharyngeal candidiasis (OPC) is a common oral opportunistic infection among
      human immunodeficiency virus (HIV)-positive individuals. Although most cases of
      OPC correlate with reduced systemic levels of CD4(+) T cells, the role of humoral
      immunity in protection against mucosal candidiasis, including OPC, remains
      questionable. In the present study, a comprehensive analysis of saliva from 33
      HIV-negative and 68 HIV-positive individuals, stratified by OPC status and
      peripheral CD4(+) cell count, was conducted to measure levels of total and
      Candida-specific immunoglobulin A(IgA) and IgG antibodies, including subclasses
      and secretory IgA. Despite changes in total immunoglobulin levels, when levels of
      Candida-specific antibodies were normalized to total protein or total
      immunoglobulin of the corresponding isotype, no distinct differences in IgG
      (including subclasses), IgA (including subclasses), or secretory IgA levels were
      seen, regardless of HIV status, OPC status, or CD4(+) cell count. These data
      suggest that when a complete repertoire of antibodies is evaluated, with
      appropriate normalization of data, there is no evidence of appreciable changes in
      levels of Candida-specific antibodies in saliva that would account for the
      prevalence of OPC among HIV-positive individuals.

PMID- 12001045
TI  - Induction of cross-reactive antibodies by immunization of healthy adults with
      types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate
      vaccines.
AB  - Types Ia and Ib group B streptococcal (GBS) capsular polysaccharides (PSs) are
      structural isomers but are antigenically distinct. Immunization of healthy adults
      with GBS type Ia PS-tetanus toxoid (Ia-TT) or Ib-TT glycoconjugate vaccines
      induced > or = 4-fold increases in specific immunoglobulin G to the heterologous
      PS in more than two-thirds of subjects. Ib-TT vaccine-induced IgG bound with
      substantially higher affinity to homologous (Ib) than to heterologous (Ia) PS and
      promoted opsonophagocytic killing of GBS type Ib but not type Ia organisms. The
      failure of the Ib-TT- and Ia-TT-induced human antibodies to kill bacteria of the
      cross-reactive serotype contrasts with the results of previous studies in
      animals. Inhibition enzyme-linked immunosorbent assays demonstrated that Ib-TT
      induced IgG to the homologous PS bound mainly to native Ib PS, whereas the cross
      reactive antibodies recognized both native and derivative PSs. These results
      indicate that GBS Ia and Ib PSs should be included in a multivalent conjugate
      vaccine to prevent GBS disease.

PMID- 12001046
TI  - Adhesion and virulence properties of epidemic Canadian methicillin-resistant
      Staphylococcus aureus strain 1: identification of novel adhesion functions
      associated with plasmin-sensitive surface protein.
AB  - Epidemic Canadian methicillin-resistant Staphylococcus aureus strain 1 (CMRSA-1)
      comprises related subtypes that differ in phenotype and prevalence, with subtypes
      1A, 1B, and 1D representing 1%, 71%, and 18%, respectively, of total CMRSA-1
      isolates. The predominant CMRSA-1B subtype possesses a variant of the
      staphylococcal cassette chromosome mec, harboring pls, which encodes plasmin
      sensitive surface protein (Pls). CMRSA-1B cells that express Pls exhibited poor
      adhesion to keratinocyte extracellular matrix. However, CMRSA-1B and purified Pls
      adhered to cellular lipids and glycolipids, and Pls promoted bacterial cell-cell
      interactions. Although exoprotein expression was restricted to a precursor form
      of lipase in CMRSA-1B, it was not attenuated in virulence relative to CMRSA-1A,
      which exhibits normal exoprotein expression. In contrast, CMRSA-1D exhibited a
      pleiotropic defect in exoprotein expression and attenuated virulence relative to
      CMRSA-1A. These data indicate that the high transmissibility of CMRSA-1B was not
      achieved at the expense of attenuated virulence and that Pls confers a novel
      adhesion mechanism.

PMID- 12001047
TI  - Clostridium difficile toxin A alters in vitro-adherent neutrophil morphology and
      function.
AB  - The effects of purified toxin A in vitro on the shape and function of
      polymorphonuclear leukocytes (PMNL) were examined. Toxin A induced changes in
      adherent PMNL shape from a compact spherical or pyramidal shape to a thin and
      rope-like shape. This change in shape was accompanied by rearrangement of the F
      actin cytoskeleton into aggregates. Toxin A-treated PMNL exhibited increased
      adherence and expressed less L-selectin and more Mac-1, compared with untreated
      PMNL. In contrast to these proinflammatory actions, toxin A impaired both
      directed and non-directed PMNL migration in response to N
      formylmethionylleucylphenylalanine. In addition, toxin A decreased the oxidative
      activity of adherent PMNL stimulated by recombinant human tumor necrosis factor
      alpha. These effects could be explained by toxin A-induced glucosylation of the
      signaling small-size guanine 5'-triphosphate-binding proteins of the Rho family
      in human PMNL.

PMID- 12001048
TI  - Characterization of vaginal flora and bacterial vaginosis in women who have sex
      with women.
AB  - Bacterial vaginosis (BV) may be common among women who report having sex with
      women (WSW) and frequently occurs in both members of monogamous couples. The
      results of Gram staining of a vaginal smear were consistent with BV in 81 (25%)
      and intermediate in 37 (11%) of 326 WSW included in this study. Lactobacilli were
      detected in 64% of subjects, and 42% of subjects had H(2)O(2)-producing strains.
      BV was associated with a higher lifetime number of female sex partners, failure
      to always clean an insertive sex toy before use, and oral-anal sex with female
      partners. Neither recent douching nor sexual practices with male partners were
      associated with BV. Vaginal smears from each partner were concordant in 55 (95%)
      of 58 monogamous couples; BV was present in both partners in 16 couples (28%)
      (P<.001, compared with expected distribution). BV was common among subjects who
      did not douche, who did not have concurrent sex with male partners, or who did
      not have a new sex partner, which suggests that other risk factors for BV exist.
      These data support the hypothesis that sexual exchange of vaginal secretions is a
      possible mechanism for acquisition of BV.

PMID- 12001049
TI  - Effect of antipyretic agents on uptake, transport, and release of antimicrobial
      agents by human polymorphonuclear leukocytes.
AB  - Polymorphonuclear leukocytes (PMNL) concentrate, transport, and release certain
      antimicrobial agents as they move in a chemotactic gradient. Antipyretic agents
      are frequently used in febrile patients receiving antimicrobial agents. Thus, the
      influence of ibuprofen, acetaminophen, and acetylsalicylic acid on uptake,
      transport, and release of azithromycin and moxifloxacin was studied. Uptake of
      the antimicrobial agents by human PMNL and the effect of the antipyretics were
      quantitated by bioassay of released antimicrobial agent. Transport and release
      were determined in chemotactic plates overlaid with sentinel bacteria that could
      detect transported and released antimicrobial agent. None of the antipyretics
      altered PMNL directed or non-directed movement. Uptake of azithromycin was
      significantly inhibited by acetylsalicylic acid but not by the other
      antipyretics. All of the antipyretic agents studied at therapeutic levels
      inhibited transport and release of both azithromycin and moxifloxacin.
      Administration of any of these antipyretic agents with antimicrobial agents that
      are transported and released by PMNL could compromise the efficacy of therapy.

PMID- 12001050
TI  - Infectivity of a Cryptosporidium parvum isolate of cervine origin for healthy
      adults and interferon-gamma knockout mice.
AB  - The infectivity of a Cryptosporidium parvum isolate of cervine origin (type 2,
      Moredun) propagated in calves was investigated simultaneously in healthy adult
      human volunteers and in interferon-gamma knockout (GKO) mice. After exposure to
      100-3000 oocysts, 16 volunteers recorded, for a duration of 6 weeks, the number
      and form of stools that they passed and any symptoms that they experienced.
      Oocyst excretion was assessed by enzyme-linked immunosorbent assay and direct
      immunofluorescence assay. Eleven subjects (69%) became ill, and 8 subjects (50%)
      shed oocysts in stool. The median duration of illness was 169 h, and the median
      number of unformed stools passed was 24. The duration and intensity of symptoms
      were more severe than were those associated with previously studied isolates. The
      median infectious dose was estimated to be 300 oocysts for humans and 1 oocyst
      for the GKO mouse model. The Moredun isolate was more pathogenic than the
      reference GCH-1 isolate. The GKO mouse model of cryptosporidiosis is useful for
      discerning isolate-specific differences in pathogenicity.

PMID- 12001051
TI  - Pulmonary manifestations of uncomplicated falciparum and vivax malaria: cough,
      small airways obstruction, impaired gas transfer, and increased pulmonary
      phagocytic activity.
AB  - Despite recognition of acute respiratory distress syndrome in both falciparum and
      vivax malaria, disease-related changes in pulmonary function have not been
      defined, and underlying mechanisms are not well understood. Respiratory symptoms,
      pulmonary function, pulmonary phagocytic cell activity, and longitudinal changes
      were examined in 26 adults with uncomplicated falciparum, vivax, and ovale
      malaria after treatment. Self-limiting cough occurred in both falciparum (36%)
      and vivax or ovale (53%) malaria. In infection with each malaria species,
      admission measures of airflow and gas transfer were lower than predicted, and
      mean lung (99m)technetium-sulfur-colloid uptake was significantly increased.
      Changes were most evident in falciparum malaria, with treatment resulting in
      initial worsening of airflow obstruction and gas transfer. Altered pulmonary
      function in malaria is common and includes airflow obstruction, impaired
      ventilation, impaired gas transfer, and increased pulmonary phagocytic activity,
      and its occurrence in both vivax and falciparum malaria suggests that there may
      be common underlying inflammatory mechanisms.

PMID- 12001052
TI  - Norwalk virus infection and disease is associated with ABO histo-blood group
      type.
AB  - Some people are resistant to Norwalk virus (NV) infection; however, the factor(s)
      responsible for resistance or susceptibility to NV infection has not been
      identified. This study investigated the relationship between a person's ABO histo
      blood group type and the risk of NV infection and symptomatic disease after
      clinical challenge. ABO phenotypes were identified by using serum samples from
      volunteers who participated in an NV challenge study (n=51). Individuals with an
      O phenotype were more likely to be infected with NV (odds ratio [OR], 11.8; 95%
      confidence interval [CI], 1.3-103), whereas persons with a B histo-blood group
      antigen had decreased risk of infection (OR, 0.096; 95% CI, 0.16-0.56) and
      symptomatic disease (OR, 0; 95% CI, 0-0.999). This is the first report
      demonstrating an association between a genetic factor and the risk of NV
      infection and symptomatic disease.

PMID- 12001053
TI  - Rhinovirus and coronavirus infection-associated hospitalizations among older
      adults.
AB  - Rhinoviruses and coronaviruses are recognized as the major causes of the common
      cold syndrome. The role of these viruses in more serious respiratory illnesses
      resulting in hospitalization is less well defined. During a winter when influenza
      A infection was prevalent, 100 elderly adults hospitalized because of
      cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus
      infection. Patients who tested negative for influenza or respiratory syncytial
      virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and
      coronavirus 229E by reverse-transcription polymerase chain reaction and for
      coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or
      coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients;
      coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1
      patient). All patients had significant underlying diseases. Although all patients
      recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1
      required ventilator support. These data suggest that rhinoviruses and
      coronaviruses may be associated with serious respiratory illnesses in frail older
      adults.

PMID- 12001054
TI  - Genetic heterogeneity of hepatitis E virus recovered from Japanese patients with
      acute sporadic hepatitis.
AB  - The recent discovery of a presumably Japan-indigenous hepatitis E virus (HEV)
      strain (JRA1) spurred analysis of additional isolates from 7 cases of acute
      sporadic hepatitis E infection. Comparison of a 326-nucleotide region from open
      reading frame 1 indicated that 1, 3, and 3 isolates segregated to genotypes I,
      III, and IV, respectively. Six patients had not traveled abroad recently. One
      patient had traveled to Hawaii 1 month before becoming ill, and the nucleotide
      sequence of the HEV isolate infecting her resembled those of US isolates (89%-91%
      nucleotide identity). However, the isolate was even more homologous to 2 other
      Japanese isolates (95%-97% nucleotide identity), suggesting that it is more
      likely a domestic, rather than an imported, strain. Three genotype IV isolates
      from Japan also had a higher homology to each other (100% amino acid identity)
      than to 2 Chinese isolates (97%-98% amino acid identity). These findings suggest
      that HEV strains of at least 3 different genotypes have already made inroads and
      are spreading in Japan.

PMID- 12001055
TI  - Elevated levels of anti-CD9 antibodies in the cerebrospinal fluid of patients
      with subacute sclerosing panencephalitis.
AB  - Subacute sclerosing panencephalitis (SSPE) is a slowly progressive and highly
      lethal disease of the central nervous system. Although the primary cause of SSPE
      is believed to be persistent infection of neuron and glial cells by a measles
      virus, the precise mechanism of the progression of this disease has not yet been
      elucidated. CD9, a member of the tetraspanin family, is expressed in myelin and
      other nervous tissues. This study detected significant amounts of anti-CD9
      antibodies in the cerebrospinal fluid (CSF) of all patients with SSPE included in
      the study. Anti-CD9 antibodies were also detected in the CSF of some patients
      with other neurologic disorders, but those patients had lower levels of anti-CD9
      antibodies than did the patients with SSPE. The level of anti-CD9 antibodies was
      elevated and reached a peak that coincided with the appearance of brain atrophy.
      These findings shed light on a new aspect of the causes and progression of SSPE.

PMID- 12001056
TI  - Chemokine receptor gene polymorphisms and risk of human T lymphotropic virus type
      I infection in Jamaica.
AB  - Polymorphisms of some chemokine receptor genes and their ligands are associated
      with susceptibility and progression of human immunodeficiency virus infection.
      This study assessed whether these variants are also responsible for
      susceptibility to infection with human T lymphotropic virus (HTLV) type I.
      Frequencies of CCR5-Delta 32, CCR2-64I, and SDF-1-3'A genotype among 116 HTLV-I
      positive and 126 HTLV-I-negative persons of African descent in Jamaica were 1.0%,
      14.9%, and 5.4%, respectively. The association of HTLV-I infection with the most
      common variant, CCR2-64I, was examined in 532 subjects. Thirteen (5.4%) of 241
      HTLV-I-negative subjects were homozygous for CCR2-64I, versus 3 (1.0%) of 291
      HTLV-I-positive subjects (P=.005). Among HTLV-I carriers, provirus load and
      antibody titer were not significantly different in persons with CCR2-+/64I or
      CCR2-+/+. These findings suggest that CCR2-64I, or alleles in linkage
      disequilibrium with it, may affect the risk of HTLV-I infection in a recessive
      manner.

PMID- 12001057
TI  - Low levels of perforin expression in CD8+ T lymphocyte granules in lymphoid
      tissue during acute human immunodeficiency virus type 1 infection.
AB  - Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte (CTL)
      responses are detectable shortly after the acute phase of HIV infection, but they
      cannot control viral replication and prevent development of chronic immune
      suppression. This article describes a defect in the coexpression of perforin in
      granzyme A-positive CD8(+) T cells in lymphoid tissue from patients with acute
      HIV infection and a reduction in the perforin-dependent nuclear translocation of
      granzyme A. Furthermore, intracellular levels of HIV DNA and RNA found in
      lymphoid tissue were higher (10-100 times) than those found in blood, and blood
      samples showed more-coordinated cellular perforin/granzyme A expression. This
      suggests that mechanisms inhibiting CTL-mediated cytotoxicity are operative in
      lymphoid tissue early in the course of HIV infection.

PMID- 12001058
TI  - Safety, tolerability, and pharmacokinetic effects of thalidomide in patients
      infected with human immunodeficiency virus: AIDS Clinical Trials Group 267.
AB  - Thalidomide is used to treat human immunodeficiency virus (HIV)-associated
      conditions, including aphthous ulcers and wasting syndrome. The safety,
      tolerability, and pharmacokinetics of a formulation of thalidomide with improved
      bioavailability in HIV-infected persons was examined in a placebo-controlled,
      dose-escalating phase 1 study. Subjects with CD4 cell counts of 200-500
      cells/mm(3) were enrolled and randomized 3:1 in groups of 12 to receive 50, 100,
      or 150 mg of thalidomide or matching placebo. Two subjects who received 150 mg of
      drug and 2 subjects assigned placebo experienced dose-limiting toxicity.
      Concentrations of thalidomide in the blood increased with escalating dose, but
      the time to maximum concentration and clearance did not differ across dose
      cohorts. Previous suggestions of autoinduction of drug metabolism were not
      confirmed by this study. At the doses studied, thalidomide was tolerated well and
      had linear pharmacokinetics.

PMID- 12001059
TI  - Recurrent invasive pneumococcal disease in individuals with human
      immunodeficiency virus infection.
AB  - The proportion of relapses and reinfections that are potentially preventable by
      vaccine in human immunodeficiency virus (HIV)-infected persons with recurrent
      pneumococcal disease is unknown. Isolates from HIV-infected individuals from
      Baltimore with recurrent pneumococcal invasive disease were collected from 1
      January 1995 through 31 December 2000. Serotyping and pulsed-field gel
      electrophoresis were performed. From 1 January 1995 through 31 December 1998,
      14.9% (404/2717) of those who had a pneumococcal infection were HIV infected. The
      recurrence rate among HIV-infected individuals was 6.4-fold higher than that
      among individuals without HIV infection (P<.01). Among recurrent infections in 41
      individuals, there were 42 reinfections and 6 relapses. All relapses and 91%
      (70/77) of reinfections were due to serotypes covered by the 23-valent
      pneumococcal polysaccharide vaccine. Reinfection was more common than relapse
      among HIV-infected individuals with recurrent pneumococcal disease. Although a
      substantial proportion of recurrent pneumococcal infections was potentially
      preventable by vaccine, creating an effective vaccine may be challenging for this
      population.

PMID- 12001060
TI  - Lactobacillus fermentum RC-14 inhibits Staphylococcus aureus infection of
      surgical implants in rats.
AB  - Staphylococcus aureus is a common cause of community and hospital-acquired
      infections. Moreover, the clinical impact of S. aureus is on the rise because of
      the global increase in the incidence of multidrug-resistant strains and its
      growing prevalence as a major cause of surgical infections. As a result, there is
      a pressing need to identify new antistaphylococcal agents and preventative
      strategies that will help in the management of these types of infections. This
      report describes the successful use of a probiotic, Lactobacillus fermentum RC
      14, and its secreted biosurfactant to inhibit surgical implant infections caused
      by S. aureus. L. fermentum RC-14 and its secreted biosurfactant both
      significantly inhibited S. aureus infection and bacteria adherence to surgical
      implants.

PMID- 12001062
TI  - Association between secondary mutations in human immunodeficiency virus type 1
      protease and therapeutic outcome.

PMID- 12001061
TI  - Recombinant Paragonimus westermani yolk ferritin is a useful serodiagnostic
      antigen.
AB  - A recombinant protein of Paragonimus westermani yolk ferritin was bacterially
      produced from a previously cloned complementary DNA and was used as an antigen
      for an enzyme-linked immunosorbent assay (ELISA) against paragonimiasis- and
      other helminth-infected sera to evaluate its serodiagnostic potential. The ELISA
      revealed that paragonimiasis westermani had 88.2% sensitivity and 100%
      specificity. The positive and negative predictive values of the ELISA were
      calculated to be 100% and 97.1%, respectively. Sera from cats experimentally
      infected with P. westermani began to produce immunoglobulin G antibodies against
      the yolk ferritin at 13 weeks after infection, which suggests that the
      corresponding antigen was derived from the vitellaria in accordance with
      maturation of P. westermani. These results indicate that the recombinant P.
      westermani yolk ferritin is a potent serodiagnostic reagent for paragonimiasis
      westermani from an early stage of the infection.

PMID- 12001064
TI  - CDC-25.1 regulates germline proliferation in Caenorhabditis elegans.
AB  - The cell cycles in C. elegans are tightly controlled but appear to use the same
      regulators found in other organisms. Four homologues of the dual-specificity
      phosphatase Cdc25 are present in the C. elegans genome. In our study, we have
      characterized a deletion mutant for one of these orthologues. We show that
      embryonic defects are absent in cdc-25.1 homozygous mutants, presumably because
      of maternally contributed CDC-25.1 product. These embryos hatch and develop into
      sterile adults. The adults do not appear to have any somatic defects. The
      sterility results from inadequate germline proliferation. Germline precursors
      divide slowly and produce abnormally sized daughter cells. Only three to four
      rounds of germ-cell division occur before they die during the L3 and L4 larval
      stages.

PMID- 12001065
TI  - Embryonic expression and regulation of the large zinc finger protein KRC.
AB  - KRC fusion proteins bind to the kappaB enhancer motif and to the signal sequences
      of V(D)J recombination. Here we have characterized endogenous KRC in mouse
      embryos and lymphoma cell lines. Starting from midgestation, neuronal- and
      lymphoid-restricted expression of KRC was observed from the dorsal root ganglia,
      trigeminal ganglion, thymus, and cerebral cortex. Several B-cell lines produced
      an alternatively spliced KRC transcript of 4.5 kb and a 115-kDa DNA-binding
      protein isoform. Additionally, that KRC transcript was induced by
      lipopolysaccharide, a potent activator of cells in immunity and inflammation. In
      genetic-engineered B cells stably transfected with inducible expression vectors
      for the recombination activating genes RAG1, RAG2, or both, the avidity of KRC to
      DNA was markedly decreased when RAG1 and RAG2 were overexpressed. We hypothesize
      that KRC may function in developing thymocytes and neurons, where its role might
      be transcription regulation or DNA recombination.

PMID- 12001066
TI  - Segmentation defects of Notch pathway mutants and absence of a synergistic
      phenotype in lunatic fringe/radical fringe double mutant mice.
AB  - The Notch signaling pathway is important in regulating formation and anterior
      posterior patterning of somites in vertebrate embryos. Here we show that distinct
      segmentation defects are displayed in embryos mutant for the Notch pathway genes
      Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3). Lfng
      deficient mice and Dll3-deficient mice exhibit very similar defects, and marker
      analysis suggests that progression of the segmentation clock is disrupted in Dll3
      mutants. We also show that Radical fringe (Rfng)-deficient mice exhibit no
      obvious phenotypic defects. To assess whether the absence of a phenotype in Rfng
      deficient mice was the result of functional redundancy with the Lfng gene, we
      generated Lfng/Rfng double homozygous mutant mice. These mice exhibit the
      skeletal defects normally observed in Lfng-deficient mice, but we detected no
      obvious synergistic or additive effects in the double mutant animals.

PMID- 12001067
TI  - Developmental potential and survival of glycolysis-deficient cells in fetal mouse
      chimeras.
AB  - Mouse embryos homozygous for a null allele of Gpi1 fail to complete gastrulation
      and die around E7.5. We produced E12.5 chimeric mouse conceptuses, composed of
      wild-type and homozygous Gpi1m/m null mutant cells to test whether the presence
      of wild-type cells allowed mutant cells to survive and, if so, whether they
      survived better in some tissue locations than others. Fourteen homozygous
      Gpi1m/m<-->Gpi1c/c chimeras were identified and these contained low levels of
      homozygous mutant cells in most tissues tested. Homozygous Gpi1m/m cells
      contributed better to the yolk sac endoderm and placenta than to the epiblast
      derivatives tested (retinal pigment epithelium, brain, tail, amnion, and yolk sac
      mesoderm). The depletion of mutant cells confirms that the gene acts cell
      autonomously, but the GPI deficiency is not always cell-lethal. When mixed with
      wild-type cells in chimeras, homozygous mutant cells can differentiate into many
      different cell types and survive until at least E12.5.

PMID- 12001068
TI  - A Vestigial:Scalloped TEA domain chimera rescues the wing phenotype of a
      scalloped mutation in Drosophila melanogaster.
AB  - The development of the Drosophila wing requires both scalloped and vestigial
      functions. Using a fusion between full-length Vestigial and the Scalloped TEA
      domain, the fusion protein can rescue scalloped wing mutations because within
      wing development, Scalloped and Vestigial cooperatively act as a transcription
      complex. Scalloped provides the necessary DNA binding function via the TEA domain
      and Vestigial promotes the activation of target genes. We also demonstrate that
      the putative nuclear localization signal contained in the TEA domain of Scalloped
      is likely responsible for the nuclear localization of Vestigial. The fusion
      protein is also capable of activating a known target gene of the native complex
      and thus represents a tool that will be helpful in rapidly identifying target
      genes of the Sd/Vg complex that are involved in wing differentiation. The
      functionality of the fusion suggests that only the TEA domain of Scalloped is
      critical for wing development and the rest of the protein (about 70%) is
      dispensable. This result is novel and should stimulate further studies of sd in
      other tissues in view of the fact that scalloped is a vital gene in Drosophila.

PMID- 12001069
TI  - Induced DNA recombination by Cre recombinase protein transduction.
AB  - Cre is a DNA recombinase that recognizes 34 base-pair loxP sites of
      recombination. We have developed a cell-permeable Cre recombinase, TATCre, that
      is capable of mediating deletion of loxP-flanked targets by simply adding TATCre
      to cell cultures. Thus, TATCre allows efficient induced DNA recombination without
      the use of a Cre recombinase transgene or any other genetic material and should
      prove useful for the genetic manipulation of a wide variety of cell types that
      have been engineered to possess loxP sites.

PMID- 12001070
TI  - Significance of clinical stage, extent of surgery, and pathologic findings in
      metastatic cutaneous squamous carcinoma of the parotid gland.
AB  - BACKGROUND: Metastatic cutaneous cancer is the most common parotid malignancy in
      Australia, with metastatic squamous carcinoma (SCC) occurring most frequently.
      There are limitations in the current TNM staging system for metastatic cutaneous
      malignancy, because all patients with nodal metastases are simply designated N1,
      irrespective of the extent of disease. The aim of this study was to analyze the
      influence of clinical stage, extent of surgery, and pathologic findings on
      outcome after parotidectomy for metastatic SCC by applying a new staging system
      that separates metastatic disease in the parotid from metastatic disease in the
      neck. METHODS: A prospectively documented series of 87 patients treated by one of
      the authors (COB) over 12 years for clinical metastatic cutaneous SCC involving
      the parotid gland and a minimum of 2 years follow-up was analyzed. These patients
      were all previously untreated and were restaged according to the clinical extent
      of disease in the parotid gland in the following manner. P1, metastatic SCC of
      the parotid up to 3 cm in diameter; P2, tumor greater than 3 cm up to 6 cm in
      diameter or multiple metastatic parotid nodes; P3, tumor greater than 6 cm in
      diameter, VII nerve palsy, or skull base invasion. Neck disease was staged in the
      following manner: N0, no clinical metastatic disease in the neck; N1, a single
      ipsilateral metastatic neck node less than 3 cm in diameter; N2, multiple
      metastatic nodes or any node greater than 3 cm in diameter. RESULTS: Clinical P
      stages were P1, 43 patients; P2, 35 patients; and P3, 9 patients. A total of 21
      patients (24%) had clinically positive neck nodes. Among these, 11 were N1, and
      10 were N2. Conservative parotidectomies were carried out in 71 of 87 patients
      (82%), and 8 of these had involved surgical margins (11%). Radical parotidectomy
      sacrificing the facial nerve was performed in 16 patients, and 6 (38%) had
      positive margins, (p <.01 compared with conservative resections). Margins were
      positive in 12% of patients staged P1, 14% of those staged P2, and 44% of those
      staged P3 (p <.05). Multivariate analysis demonstrated that increasing P stage,
      positive margins, and a failure to have postoperative radiotherapy independently
      predicted for decreased control in the parotid region. Survival did not correlate
      with P stage; however, many patients staged P1 and P2 also had metastatic disease
      in the neck. Clinical and pathologic N stage both significantly influenced
      survival, and patients with N2 disease had a much worse prognosis than patients
      with negative necks or only a single positive node. Independent risk factors for
      survival by multivariate analysis were positive surgical margins and the presence
      of advanced (N2) clinical and pathologic neck disease. CONCLUSIONS: The results
      of this study demonstrate that patients with metastatic cutaneous SCC in both the
      parotid gland and neck have a significantly worse prognosis than those with
      disease in the parotid gland alone. Furthermore, patients with cervical nodes
      larger than 3 cm in diameter or with multiple positive neck nodes have a
      significantly worse prognosis than those with only a single positive node. Also,
      the extent of metastatic disease in the parotid gland correlated with the local
      control rate. The authors recommend that the clinical staging system for
      cutaneous SCC of the head and neck should separate parotid (P) and neck disease
      (N) and that the proposed staging system should be tested in a larger study
      population.

PMID- 12001071
TI  - Combined endovascular and surgical treatment of head and neck paragangliomas--a
      team approach.
AB  - BACKGROUND: Paragangliomas are highly vascular tumors of neural crest origin that
      involve the walls of blood vessels or specific nerves within the head and neck.
      They may be multicentric, and they are rarely malignant. Surgery is the preferred
      treatment, and these tumors frequently extend to the skull base. There has been
      controversy concerning the role of preoperative angiography and embolization of
      these tumors and the benefits that these procedures offer in the evaluation and
      management of paragangliomas. METHODS: Forty-seven patients with 53
      paragangliomas were treated from the period of 1990-2000. Initial evaluation
      usually included CT and/or MRI. All patients underwent bilateral carotid
      angiography, embolization of the tumor nidus, and cerebral angiography to define
      the patency of the circle of Willis. Carotid occlusion studies were performed
      with the patient under neuroleptic anesthesia when indicated. The tumors were
      excised within 48 hours of embolization. RESULTS: Carotid body tumors represented
      the most common paraganglioma, accounting for 28 tumors (53%). All patients
      underwent angiography and embolization with six patients (13%), demonstrating
      complications (three of these patients had embolized tumor involving the affected
      nerves). Cerebral angiography was performed in 28 patients, and 5 of these
      patients underwent and tolerated carotid occlusion studies. The range of mean
      blood loss according to tumor type was 450 to 517 mL. Postoperative cranial nerve
      dysfunction depended on the tumor type resected. Carotid body tumor surgery
      frequently required sympathetic chain resection (21%), with jugular and vagal
      paraganglioma removal frequently resulting in lower cranial nerve resection.
      These patients required various modes of postoperative rehabilitation, especially
      vocal cord medialization and swallowing therapy. CONCLUSIONS: The combined
      endovascular and surgical treatment of paragangliomas is acceptably safe and
      effective for treating these highly vascular neoplasms. Adequate resection may
      often require sacrifice of one or more cranial nerves, and appropriate
      rehabilitation is important in the treatment regimen.

PMID- 12001072
TI  - Functional assessment using Constant's Shoulder Scale after modified radical and
      selective neck dissection.
AB  - BACKGROUND: Constant's Shoulder Scale is a validated and widely applied
      instrument for assessment of shoulder function. We used this instrument to assess
      which treatment and demographic variables contribute to shoulder dysfunction
      after neck dissection in head and neck cancer patients. METHODS: A convenience
      sample of 54 patients with 64 neck dissections and minimum follow-up of 11 months
      were evaluated. Thirty-two accessory nerve-sparing modified radical (MRND) and 32
      selective neck (SND) dissections were performed. Multivariable regression
      analysis was used to determine the variables that were predictive for shoulder
      dysfunction. Clinical variables included age, time from surgery, handedness,
      weight, radiation therapy, neck dissection type, tumor stage, and site. RESULTS:
      Patients receiving MRND had significantly worse shoulder function than patients
      with SND (p =.0007). Radiation therapy contributed negatively, whereas weight
      contributed positively (p =.0001). CONCLUSIONS: The critical factors contributing
      to shoulder dysfunction after neck dissection were weight, radiation therapy, and
      neck dissection type.

PMID- 12001073
TI  - Prediction of survival in patients with head and neck cancer using the
      histoculture drug response assay.
AB  - BACKGROUND: Chemoresponse is a significant outcome predictor in patients with
      head and neck cancer, regardless of the treatment modality used. The histoculture
      drug response assay (HDRA) has been shown to be a reliable method for in vitro
      chemoresponse assessment. In this study, we have correlated the HDRA assessment
      with survival in patients with head and neck squamous cell carcinoma (HNSCC).
      METHOD: Tumor specimens from 41 of 42 patients undergoing treatment for HNSCC
      were successfully evaluated by the HDRA. Tumor tissue was histocultured on
      Gelfoam sponges gel in 24-well plates, followed by treatment with cisplatin (15
      microg/mL) or 5-fluorouracil (40 microg/mL) in triplicate. A control group
      received no drug treatment. After completion of drug treatment, the relative cell
      survival in the tumors was determined using the MTT assay. The inhibition rate
      (IR) for each drug was calculated relative to the control for each case, and
      sensitivity was defined as a tumor IR of greater than 30%. Treatment was based on
      established protocols for the location and stage of the tumor and included
      surgery, radiation, and/or chemotherapy. Survival comparisons were performed
      using the generalized Wilcoxon test for the comparison of Kaplan-Meier survival
      curves. RESULTS: Resistance to 5-fluorouracil was present in 13 cases (32%), to
      cisplatinum in 13 cases (32%), and to both agents in 11 cases (27%). The 2-year
      cause-specific survival was significantly greater for patients sensitive to 5
      fluorouracil (85% vs 64%; p =.04), cisplatinum (86% vs 64%; p =.05), or both
      agents (85% vs 63%; p =.01). The association between HDRA assessment of
      chemoresponse and clinical outcome remained significant even after controlling
      for the effects of TNM stage and the presence of recurrent cancer at presentation
      by multivariate analysis. CONCLUSIONS: Chemosensitivity determined by the HDRA
      seems to be a strong predictor of survival in patients with advanced HNSCC and
      should be considered further.

PMID- 12001074
TI  - Role of Epstein-Barr virus and cytomegalovirus in the etiology of benign parotid
      tumors.
AB  - BACKGROUND: Pleomorphic adenomas and Warthin's tumors are the two most common
      benign parotid tumors. Previous studies investigating the role of viruses in
      tumorigenesis of these neoplasms have been conflicting. The aim of this study was
      to determine whether Epstein-Barr virus (EBV) or cytomegalovirus (CMV) might play
      a role in the pathogenesis of pleomorphic adenomas and Warthin's tumors. METHODS:
      Paraffin-embedded surgical specimens of 24 pleomorphic adenomas, 10 Warthin's
      tumors, and 13 normal parotid tissues were obtained from the University of
      California-San Francisco Pathology Department. Genomic DNA was extracted from the
      specimens, and primers for connexin 26, a gap junction protein, were used to
      confirm the integrity of this DNA. The presence or absence of EBV and CMV DNA
      within the samples was determined with PCR-based assays, in which radiolabeled
      primers were used for maximal sensitivity of detection. RESULTS: PCR analysis of
      serially diluted control DNA revealed that using radiolabeled primers, five
      copies of viral DNA could be detected. By use of this method, we showed that none
      of the 24 pleomorphic adenomas, 10 Warthin's tumors, or 13 normal parotid samples
      contained EBV DNA or CMV DNA. CONCLUSIONS: These results do not support CMV or
      EBV as etiologic factors in pleomorphic adenomas or Warthin's tumors. In
      addition, normal parotid seems not to harbor either of these viruses. Future
      studies with larger numbers of specimens are needed to confirm these findings.

PMID- 12001075
TI  - Evaluating the donor site after harvest of free jejunum grafts.
AB  - BACKGROUND: Free jejunal grafts are commonly used for reconstruction after
      surgery for hypopharyngeal and cervical esophageal cancer. However, few reports
      have addressed postoperative morbidity at the abdominal donor site. METHODS:
      Preoperative morbidity and postoperative complications were analyzed in 126
      patients in whom free jejunal grafts had been harvested from 1992 through 1996.
      RESULTS: Although 27 patients had previously undergone abdominal surgery, there
      was no correlation between previous abdominal surgery and abdominal complications
      after graft harvest (p >.25). Abdominal complications were not correlated with
      patient age (p >.25). CONCLUSIONS: Our findings suggest that previous abdominal
      surgery (except on the ileum) and patient age are not contraindications to free
      jejunal graft harvest.

PMID- 12001076
TI  - Carcinoma of the supraglottic larynx: treatment results with radiotherapy alone
      or with planned neck dissection.
AB  - PURPOSE: To present the results of radiotherapy with or without neck dissection
      for squamous cell carcinoma of the supraglottic larynx treated at the University
      of Florida and to compare these data with those obtained after conservation
      surgery. METHODS AND MATERIALS: Continuous-course radiotherapy alone or combined
      with a planned neck dissection was used to treat 274 patients with squamous cell
      carcinoma of the supraglottic larynx between 1964 and 1998. All patients had
      follow-up for a minimum of 2 years, and 250 (91%) had follow-up for 5 years or
      more. RESULTS: At 5 years, the actuarial probability of local control after
      radiotherapy according to T stage was as follows: T1, 100%; T2, 86%; T3, 62%; and
      T4, 62%. The probability of cause-specific survival at 5 years by AJCC stage was
      as follows: stage I, 100%; II, 93%; III, 81% IVA, 50%; and IVB, 13%. The risk of
      severe late complications was 4%. Of 57 patients undergoing planned
      postradiotherapy neck dissection, 7% experienced a severe complication.
      CONCLUSIONS: On the basis of our data and the literature, early or moderately
      advanced supraglottic carcinomas may be treated successfully with either
      supraglottic laryngectomy or radiotherapy. Supraglottic laryngectomy probably
      produces a higher initial local control rate but, based on anatomic and
      coexisting medical constraints, is suitable for a smaller subset of patients and
      has a higher risk of complications compared with radiotherapy.

PMID- 12001077
TI  - Prognostic factors in head and neck rhabdomyosarcoma.
AB  - BACKGROUND: Rhabdomyosarcoma comprises less than 1% of all head and neck cancer.
      The purpose of our study is to review our institutional experience in this
      disease and to identify possible prognostic factors for patients with head and
      neck rhabdomyosarcoma. METHODS: One hundred forty patients with rhabdomyosarcoma
      were identified from 1955-1999 within the tumor registry. Of these cases, 49
      (35%) were noted to be primary head and neck rhabdomyosarcomas. Retrospective
      chart reviews were completed to obtain the following data: age, gender, site,
      tumor size, histologic findings, Intergroup Rhabdomyosarcoma Study Group,
      treatment, local control, and survival. RESULTS: The 5-year overall survival and
      local control rates were 60% +/- 14% and 70% +/- 14%, respectively. Tumor size <
      or =5 cm (p =.014) and age < or =11 years (p =.036) were predictive of improved
      survival, whereas age < or =11 years was predictive of improved local control (p
      =.006). Children < or =11 years with a < or =5-cm tumor have the best overall
      survival, whereas patients >11 years with a tumor >5 cm have the worst survival.
      The 5-year survival was intermediate for children < or =11 years with a >5-cm
      tumor and patients >11 years with a < or =5-cm tumor. Radiotherapy treatment
      duration < or =45 days in group III disease was associated with improved overall
      survival but not local control. For the six patients with group I or II disease,
      who did not receive initial chemotherapy, five had relapses at the primary and/or
      distant sites. CONCLUSIONS: Improvement in outcome was obtained with
      multimodality treatment regimens for head and neck rhabdomyosarcoma. Both tumor
      size and age of patient were found to influence survival.

PMID- 12001078
TI  - Role of planned neck dissection for advanced metastatic disease in tongue base or
      tonsil squamous cell carcinoma treated with radiotherapy.
AB  - OBJECTIVE: At the conclusion of this article, the reader should be able to
      discuss the need for planned neck dissection for advanced cervical diseases in
      the tongue base and tonsil cancer after treatment with radiotherapy. BACKGROUND:
      In the past 5 years, we have treated patients with squamous cell carcinoma of the
      tonsil and tongue base with radiotherapy as the primary therapeutic modality. A
      planned complete neck dissection was performed on all patients with N2 or greater
      cervical disease regardless of response to radiotherapy. Composite resection was
      performed when there was persistent disease at the primary site. Although the
      "radiation-first" therapeutic approach for tongue base and tonsil cancer is
      widely accepted, the planned neck dissection for neck metastases remans
      controversial. The objective of the study was to determine the validity of
      planned neck dissection after radiotherapy for N2 disease. METHODS: Medical
      records of patients with primary squamous cell carcinoma of the tongue base and
      tonsil with neck metastasis staged N2 or greater were reviewed. Between 1994 and
      1999, 36 such patients were treated with curative radiation therapy. Response was
      assessed 6 to 8 weeks after completion of treatment with clinical examination and
      CT imaging. All patients underwent planned neck dissection. We reviewed the
      clinical and radiographic response of neck disease to radiotherapy as it
      correlated with the histopathologic findings. RESULTS: Of the 36 patients, 17 had
      clinical and CT evidence of persistent disease. In this group, 65% had
      pathologically confirmed diseases at surgery. Of the 9 patients with no evidence
      of disease on clinical examination, negative biopsy at the primary site, and a
      negative CT scan, 33% (three of nine) still had residual disease in the neck
      dissection specimen. CONCLUSIONS: Positive findings on clinical examination and
      CT can predict the presence of malignancy after radiation therapy. However, a
      negative CT and clinical examination are limited in predicting a complete
      response. These data lend support to the role of planned neck dissection after
      radiotherapy of N2 neck disease.

PMID- 12001079
TI  - Fetal operations in the head and neck area: current state.
AB  - BACKGROUND: Fetal surgery is defined as prenatal surgical intervention. Such
      intervention is currently considered in selected cases of fetal malformations
      that endanger the child's life prenatally or postnatally, such as death or severe
      impairment. METHODS: Current indications are reviewed, with special emphasis on
      success rates and complications, including concomitant ethical problems. Data
      sources are based on personal experience and medical information systems
      (especially MEDLINE). RESULTS AND CONCLUSIONS: In the head and neck areas,
      especially the upper respiratory tract, such procedures can be indicated in
      selected cases. They include exposure and temporary obstruction of the fetal
      trachea to reduce the viscera and to prevent pulmonary hypoplasia in congenital
      diaphragmatic hernia, prenatal tracheotomy in laryngeal atresia, and intranatal
      establishment of an airway in airway-obstructing embryonic tumors. The latter
      surgery can be performed after delivery of the fetal head and neck and before
      umbilical cord severance. This method ensures oxygenation of the fetus by the
      maternofetal circulation until completion of the surgical intervention (so called
      EXIT procedure = Ex-Utero Intrapartum Treatment). The relatively high surgical
      risk of fetal surgery, in particular postoperative preterm labor, may be reduced
      by the use of minimally invasive endoscopic techniques. By reducing operative
      risks even further, prenatal surgical interventions may even be used in nonlethal
      conditions. Consequently, more diseases of the head and neck area could thus be
      included in the spectrum of indications, such as prenatal correction of the cleft
      lip palate. Because fetal wound healing incurs no scarring up to a certain stage
      in pregnancy, such fetal surgical correction could be a perspective.

PMID- 12001080
TI  - Small cell neuroendocrine carcinoma of the maxillary sinus--a case report and
      nude mouse transplantable model.
AB  - BACKGROUND: A rare case of small cell neuroendocrine carcinoma (SNEC) arising in
      the maxillary sinus is presented, and a SNEC tumor line serially transplantable
      in nude mice was established. Tumor marker for SNEC is also discussed. METHODS:
      The tumor tissues obtained from operated material were heterotransplanted
      subcutaneously into nude mice. Histopathologic studies and immunoradiometric
      assays for NSE and pro-GRP in serum were performed. RESULTS: The primary lesion
      was composed of tumor nests of small cells with hyperchromatic nuclei and was
      positive for NSE and chromogranin A immunohistochemically. Serum levels of NSE
      and pro-GRP changed dynamically, reflecting the clinical status. Nude mouse tumor
      showed similar histologic features to those of original tumor and expressed NSE.
      Neuroendocrine granules were detected in tumor cells in electron microscopy.
      Serum NSE level in nude mice was elevated in proportion to the relative tumor
      weight. CONCLUSIONS: Serum NSE and pro-GRP were useful tumor markers for
      extrapulmonary SNEC. A SNEC tumor transplantable in nude mice would provide a
      valuable model for characterization of this lesion.

PMID- 12001081
TI  - Necrotizing fasciitis of the head and neck: a report of two patients and review.
AB  - BACKGROUND: Necrotizing fasciitis is a disfiguring condition that can be fatal.
      The head and neck region is rarely affected. However, when involved, the
      functional and cosmetic sequelae can be considerable. MATERIALS AND METHODS: We
      present two case histories, discuss salient diagnostic points, treatment, and
      review published data on this topic. RESULTS: With a timely diagnosis we were
      able to diagnose and appropriately treat these patients. CONCLUSIONS: Necrotizing
      fasciitis is a disfiguring condition that can be fatal if not diagnosed in a
      timely fashion. Diagnosis and treatment require a high index of suspicion,
      immediate operative intervention, broad-spectrum antibiotics, and appropriate
      supportive care.

PMID- 12001082
TI  - An enhanced TNM.

PMID- 12001085
TI  - New data on the genetic structure of the population of Sicily: analysis of the
      Alia population (Palermo, Italy).
AB  - The distribution of 13 genetic markers (AB0, Rh, ACP, ADA, AK, ESD, GLO, PGD,
      PGMl, SOD, GC, TF, and PI) were studied in a sample from the Alia population of
      Sicily, Italy. A total of 34 alleles were detected. In comparison with other
      Sicilian populations, Alia always appeared genetically distinctive, either in
      terms of overall genetic diversity or for the number of unique alleles present.
      The results are consistent with previous studies that show no genetic uniformity
      within the island. More specifically, the data support the genetic divergence of
      the eastern and western halves of the island and highlight genetic boundaries
      that run through Sicily and divide it into three distinct areas.

PMID- 12001086
TI  - Estimation of height in elderly Japanese using region-specific knee height
      equations.
AB  - Two knee height equations to predict standing height of Japanese elderly were
      cross-validated with Joetsu City elders. One equation was derived with Hawaiian
      residents of Japanese ancestry and the other with elders from the Kumamoto
      Prefecture in Japan. Subjects included 40 men and 39 women free-dwelling, healthy
      elders with mean ages of 68.0 +/- 2.2 years and 68.0 +/- 2.7 years, respectively.
      Heights of the subjects were representative of Japanese elderly. Experienced
      nurses, trained to measure knee height, also measured standing height with an
      automatic stadiometer. A pilot study refined measurement skills. Differences
      between actual and predicted heights for both equations were significant.
      Multiple linear regression was used to derive knee height equations specific for
      elderly males and females living in Joetsu City: women, 63.06 + (2.38 x knee
      height in cm) -(0.34 x age in years); men, 71.16 + (2.61 x knee height in cm) -
      (0.56 x age in years). Geographic-specific knee height equations for Japanese
      elderly and cross-validation with other locations are suggested to facilitate the
      accurate use of knee height in nutritional assessment of Japanese elders.

PMID- 12001087
TI  - Origin of Fueguian-Patagonians: an approach to population history and structure
      using R matrix and matrix permutation methods.
AB  - A complicated history of isolation between Fueguian and Patagonian groups
      (originated by the appearance of the Straits of Magellan) as much as differences
      in population structure and life strategies constitute important factors in the
      clustering pattern of those groups. The aim of this work was to test several
      hypotheses about population structure and history of Fueguian-Patagonians to
      propose a model that incorporates predictions for future studies. R matrix
      methods and matrix permutation analyses were performed upon a data matrix of
      craniofacial measurements of 441 skulls divided into nine samples pertaining to
      six Patagonian and three Fueguian populations. Association of biological
      distances with three matrices representing several settlement patterns was tested
      using matrix permutation tests. Results of R matrix study show that the minimum
      genetic distance obtained confirms separation between Fueguians and Patagonians.
      Moreover, an analysis of residual variances from the expected regression line
      confirms admixture between Andean and Pampean populations and Araucanian groups,
      consistent with ethnohistorical observations. A model representing a long history
      of isolation between Fueguian and Patagonians, rather than a model emphasizing
      differences in life-strategies, presented the best correlation with the
      biological distance matrix. Because similar results were already obtained in
      archaeological, molecular, and morphological studies, a model for the settlement
      of Tierra del Fuego is proposed. It is summarized by four main hypotheses that
      can be tested independently by different disciplines in the future.

PMID- 12001088
TI  - Are there ethnic differences in sleep architecture?
AB  - The possibility of ethnic differences in sleep architecture was initially
      examined in conjunction with studies of sleep apnea (study 1). This possibility
      was then examined in another cohort of patients to determine whether the results
      might generalize (study 2). Polysomnography was obtained in both cohorts as part
      of larger protocols investigating sympathetic nervous system activity, blood
      pressure, and sleep. Sleep monitoring took place in an inpatient clinical
      research center of a university hospital. Study 1 focused on sleep apnea
      physiology and involved volunteers with sleep apnea who were otherwise healthy.
      Study 2 focused on differences in stress reactivity between American Black and
      White subjects and involved hypertensive and normotensive volunteers who were
      otherwise healthy. Analyses include 61 participants from study 1 and 35
      participants from study 2. Ethnicity in both cohorts was determined by self
      report. Participants in both studies were monitored during sleep with traditional
      polysomnography including electroencephalography (EEG), electromyography (EMG),
      electrooculography (EOG), and oximetry. In Study 1, Blacks had longer TST (P <
      0.01), more REM sleep (P < 0.05), and less WASO (P < 0.05) than Whites. After
      controlling for RDI, Blacks had longer TST and spent a smaller percentage of time
      in deep sleep (P < 0.05). In study 2, Blacks had longer TST and REM sleep, lower
      percent deep sleep, and lower percent deep sleep controlling for RDI (P < 0.05).
      In two separate studies, Blacks had longer TST, more minutes of REM, and lower
      percentage deep sleep. These findings suggest possible ethnic differences in
      sleep architecture.

PMID- 12001089
TI  - Age-related pattern of body density and body composition in Japanese males and
      females, 11 and 18 years of age.
AB  - The age-related pattern of body density and body composition in Japanese males (n
      = 266) and females (n = 318), 11.00 to 18.99 years of age was studied. Body
      density (BD) as well as height, body weight, and seven skinfold thicknesses were
      measured. Percentage fat (%Fat) was calculated using the age- and sex-specific
      equation of Lohman. Fat mass (FM), fat-free mass (FFM), and the body mass index
      (BMI) were calculated. The trend for BD in males was lowest at 11 years (1.0530
      g/ml) and increased to 1.0695 g/ml at 14 years, and then decreased slightly at 15
      to 17 years. In female, BD decreased from 1.0530 g/ml at 13 years to 1.0424 g/ml
      at 17 years. Mean %Fat was highest in males at 11 years (15.8%), and lowest at 14
      years (10.1%). The highest mean %Fat in females occurred at 16 years (22.8%), and
      the lowest at age 11 years (15.2%). Overall, only 6.8% of males and 3.1% of
      females were classified as obese. Between 11 and 18 years, FFM of males differed
      by 20.7 kg or 67.9%, whereas females showed a difference of only 10.8 kg or
      34.7%. Consequently, age effects explained approximately 60% of the male variance
      of FFM but only 26% in females. Body density of each sex and age group in this
      study did not differ significantly from previous Japanese studies, and the pooled
      BD data for 1,457 Japanese including the present study are reported as a
      reference.

PMID- 12001090
TI  - Influences of chorion type on measurements of the corpus callosum in adult
      monozygotic male twins?
AB  - MRI imaging was used to estimate volumes of corpus callosum structure in 45 pairs
      of identical (monozygotic, MZ) twins from the National Heart, Lung, and Blood
      Institute (NHLBI) twin study. Age range of the study subjects was from 68-78
      years. Finger, palm, and footprint data (dermatoglyphics) collected at previous
      examinations of the NHLBI twin study were available for 39 pairs. The
      dermatoglyphics were scored for an index to retrospectively assess chorion type
      in MZ twin-pairs. The results indicated an association between variability in
      various structures of the corpus callosum with some of these dermatoglyphic
      traits, suggesting greater structural variation within pairs with dichorionic
      placentas. In contrast, total intracranial volume, which has similar heritability
      estimates as a result of shared genetic effects with the corpus callosum, was
      unrelated to the dermatoglyphic traits. The results provide indirect evidence
      that the intrauterine environment may influence twin-pair similarity of corpus
      callosum measures in adults.

PMID- 12001091
TI  - New STR at the D5S373 locus and its relevance in human population studies.
AB  - The genetic analysis of a new trinucleotide repeat (D5S373) was carried out with
      a view to its application in both individual genetic profiling and human
      population genetics. In a screening analysis from seven world populations (n =
      706) and after nucleotide sequence analysis, up to nine alleles were found
      corresponding to 8-13 repetitions of a TAA motif. This analysis shows He values
      ranging between 0.689-0.762. D5S373 reveals interpopulational variability which
      leads to specific frequency profiles in the major human groups, with alleles 8,
      11, l2, and 13 being particularly informative, which suggests the that this
      marker may be of interest in the biological study of human populations.

PMID- 12001092
TI  - Equations for predicting height for elderly Mexican Americans are not applicable
      for elderly Mexicans.
AB  - Common indices for the assessment of nutritional status take height into account.
      Elderly individuals are frequently unable to assume the position needed for this
      measurement. Therefore, equations have been developed for predicting height in
      elderly American Whites, American Blacks, and Mexican Americans using knee height
      as a predictor. These equations may not be applicable for the elderly in other
      populations. A sample of 736 individuals was studied (186 males, 550 females)
      with a mean age of 74.7 +/- 8 years. Height and knee height (without shoes) were
      measured in millimeters. Multiple regression and cross-validation was performed.
      The correlation between knee height and standing height was similar in women (r =
      0.86; P < 0.0001) and men (r = 0.83; P < 0.0001). The equations obtained were as
      follows: men (height in cm) = 52.6 + (2.17 x knee height in cm) and women (height
      in cm) = 73.7 + (1.99 x knee height in cm) - (0.23 x age in years). Cross
      validation showed that the pure error was less than the root mean square error
      (RMSE) in both sexes. Mean heights, based on the equations of Chumlea et al.
      (1998) for Mexican Americans significantly differ from the reference values for
      females and males. Therefore, the equations developed by Chumlea et al. (1998)
      for elderly Mexican Americans do not appear to be applicable for elderly
      Mexicans.

PMID- 12001093
TI  - Differential workloads of boys and girls in rural Nepal and their association
      with growth.
AB  - In developing countries, heavy workloads of women adversely affect their
      nutritional status and that of their children. Little is known, however, about
      the effect of children's heavy workloads on their own well-being. In Nepal, girls
      are expected to help their mothers in time-consuming and energy-demanding tasks
      from an early age. The aim of this study was to compare work patterns and
      anthropometric status of boys and girls age 6-17 years in western rural Nepal. It
      was hypothesized that girls would work longer and harder than boys and would have
      poorer growth status. It was also anticipated that children's work patterns might
      differ between highland and lowland areas. Two study sites were therefore chosen:
      one in the hills and the other in the lowland terai. A time allocation study was
      conducted for 237 children. They were observed continuously from 7:00 AM to 7:00
      PM to determine the time spent in light, moderate, and heavy activities. Body
      weights and heights were also measured. On average, girls worked twice as long as
      boys (5.8 vs. 2.8 h/day, P < 0.001) and undertook more heavy work (1.5 vs. 0.7
      h/day, (P < 0.001), but they did not have poorer anthropometric status. Children
      in the hills worked longer hours and did heavier work than those in the terai and
      were more stunted in growth.

PMID- 12001094
TI  - Comparison of peak muscle power between Brazilian and French girls.
AB  - This study examined the muscle power of Brazilian circumpubertal girls and
      extended the analysis to a cross-cultural dimension. A total of 462 children, 123
      Brazilian girls and 339 French girls, 9-18 years, participated in this
      investigation. Anthropometric data included body mass (BM), height, skinfold
      thicknesses, and estimated lean leg volume (LLV). All subjects completed a
      physical activity questionnaire. Cycling peak power was measured including the
      flywheel inertia of the device (CPPi). Brazilian girls self-assessed their
      maturation using pubic hair development. CPPi and optimal velocity (v(opt) =
      velocity at CPPi) increased with stages of puberty. A multiple stepwise
      regression with anthropometric variables as explanatory factors showed only LLV
      and age explaining the variance of CPPi (R2 = 0.40, P < 0.001). Therefore, 60% of
      the variance of CPPi in Brazilian girls was related to undetermined qualitative
      individual factors, which may be related to cycling skill. Even when normalized
      for anthropometric variables, the anaerobic performance (CPPi and v(opt)) of
      Brazilian girls was significantly lower than a cohort of French girls. The latter
      demonstrated a high participation in sport and training activities, while 50% of
      the Brazilian girls had only physical education classes in the form of regular
      physical activity. Moreover, most of the Brazilian girls demonstrated an
      ineffective sprint cycling skill. The data suggest that motor learning is an
      important issue in muscle power assessment and might, therefore, partially
      explain peak power differences in Brazilian compared with French girls.

PMID- 12001095
TI  - Helping patterns and reproductive success in Aymara communities.
AB  - "Helpers at the nest," young adults remaining in their parents home to take care
      of younger siblings, are known in many species of birds and mammals. Similar
      behaviors are occasionally observed in human societies but their frequency and
      significance for parental reproductive success are still not fully appraised.
      This study was designed to document this issue in a traditional Aymara peasant
      society of the Bolivian Altiplano, It is based on 359 reproductive life histories
      of women 45 years of age or older and on a survey of children's workload in 1998
      and 1999. The presence of "potential helpers" in the household is significantly
      associated with higher fertility and with improved survival of siblings to sexual
      maturity. Caretaking is not particularly assigned to older daughters. The
      positive relationship between the availability of offspring help and reproductive
      success does not demonstrate a causal role for child caretaking because, in
      contrast with nonhuman helpers, workloads of children range from housekeeping to
      agricultural tasks, instead of being focused on feeding or protecting younger
      siblings. Correlation and multiple regression analyses, however, suggest that the
      total amount of care given by the older offspring and the amount of care received
      by each recipient are, along with offspring contribution to household economy,
      among the determinants of parental reproductive success.

PMID- 12001096
TI  - Interrelationship between bone aging traits and basic anthropometric
      characteristics.
AB  - Using plain hand radiographs, the age dependence of various bone-aging traits
      (bone mineral density [BMD], cortical index [CI], osteoarthritis [OA], and
      osseographic [OSS] scores) was evaluated to test whether the correlation among
      these traits is an individual- or population-based phenomenon. In addition, the
      effect of anthropometric features on variation of bone-aging traits was
      estimated. The study included 1,295 individuals from Chuvasha, Russia, 18 to 89
      years. BMD was measured from the compact compartment of the middle and distal
      phalanges of both 3(rd) fingers. The CI of the II-IV metacarpal bones and II-IV
      proximal phalanges was obtained. The development of OA was based on the standard
      Kellgren and Lawrence grading scheme for 28 hand joints. OSS score, a surrogate
      measure that takes into account different kinds of bone changes, was also
      obtained for each individual. Body weight and height, eight skinfold thicknesses
      on the trunk and extremities, and breadths of the long bones were measured. Sex
      based univariate analyses and multivariate statistical analysis showed the
      following: 1) Age dependence was defined more strongly in "OA-linked" compared to
      "osteoporosis (OP)-linked" traits; 2) While "OP-linked" bone-aging traits
      correlated with age differently between sexes, "OA-linked" traits did not; 3) The
      strong interrelationship between OA-linked and OP-linked traits in both sexes
      became very weak and statistically insignificant (P > 0.10) after adjustment for
      age. Thus, OA and OP conditions in the same individual develop independently and
      probably reflect different underlying physiological mechanisms. 4) Anthropometric
      characteristics were significantly correlated with bone-aging traits, but
      correlations were low (r < 0.20). Thus, the contribution of anthropometric
      characteristics to the rate and pattern of bone aging of the hand was to
      relatively small.

PMID- 12001097
TI  - Use of surnames for a demo-ecological analysis: a study in southwest Sardinia.
AB  - This study used surnames collected in 12 municipalities of Sulcis, a historic
      geographical region located in southwest Sardinia (Italy). An ecological index of
      similarity was drawn as the main analysis. The distribution of surnames was also
      used to determine the diversity of municipality populations by using another
      ecological index. Two municipalities have a high percentage of Genoese surnames
      and this element reflects a specific history and culture, different from other
      Sardinian localities. These peculiarities are evident in the topological
      representation, which graphically emphasizes the links between the populations
      studied. Two other municipalities can be distinguished from the remaining eight.
      Above all, historical, socioeconomic, cultural, and geographic considerations are
      useful in the appropriate interpretation of the results.

PMID- 12001098
TI  - Infants thinner at birth exhibit smaller kidneys for their size in late gestation
      in a sample of fetuses with appropriate growth.
AB  - Fetal ultrasound measurements were employed to investigate the relationship
      between weight and ponderal index at birth and kidney size during the second (23
      weeks) and third (32 weeks) trimesters of pregnancy in a sample of 25 normally
      growing fetuses. Kidney volume and kidney volume / fetal weight ratio at 32 weeks
      are significantly and positively related to both weight and ponderal index at
      birth, controlling for sex, gestational age at birth, and day of ultrasound
      measurement. A second-degree polynomial relationship approximates the
      predictability of kidney volume fetal weight ratio at 23 weeks to that at 32
      weeks, demonstrating shifting growth rates in fetal organ and body growth
      relationships during midgestation. Sex and parental size are suggested as
      contributing to these patterns. Females have a surge in renal growth between 23
      and 32 weeks to catch up to earlier growing males, and maternal weight
      significantly predicts incremental growth in kidney volume and the kidney volume
      / fetal weight ratio at 32 weeks of gestation. The observation that fetuses
      relatively thin at birth have relatively smaller kidneys for their size in late
      gestation suggests that the influence of maternal weight on birth outcome may act
      through organ growth.

PMID- 12001107
TI  - Adenoid cystic carcinoma of the breast: molecular markers, treatment, and
      clinical outcome.
AB  - BACKGROUND: The objective of this study was to comprehensively characterize the
      clinical and biologic features of adenoid cystic carcinoma (ACC) and to assess
      the implications for management in a large cohort of patients. METHODS: From a
      database of 50,000 patients, 28 were identified with ACC for which clinical
      follow-up and biologic information was available. The biologic features examined
      included estrogen receptor and progesterone receptor status, DNA ploidy, and S
      phase fraction. Median follow-up was 83 months with a range of 29 to 144 months.
      Overall survival and disease free survival curves were drawn using Kaplan and
      Meier estimates and were compared by the log-rank test. RESULTS: All but one
      patient were postmenopausal with a median age at diagnosis of 66 years (range, 40
      96 years). One patient had macroscopic metastatic disease at diagnosis. Median
      tumor size was 1.9 cm (range, 0.5-7.0 cm). Axillary lymph node dissection was
      performed in 23 patients. Only 1 patient (4%) had histologic positive lymph nodes
      (2 of 10), and no recurrence was detected for this patient. Forty-six percent
      were ER positive (median, 16 fmol/mg protein; range, 5-1017 fmol/mg), and 35%
      were PgR positive (median, 61 fmol/mg protein; range, 6-854 fmol/mg). S-phase
      fraction and DNA ploidy were assessable in 24 cases. Ninety percent of tumors had
      low S-phase (median, 3.3%; range, 0.1-34.2%), and 92% were diploid. Simple or
      modified radical mastectomy was performed in 22 patients, and 6 patients were
      treated by lumpectomy. Five of these six patients also received radiation therapy
      after lumpectomy. Despite the different surgical approaches, there were no local
      recurrences. The 5-year disease free survival rate was 100%, and the 5-year
      overall survival rate was 85% (95% confidence interval, 71.7-98.6%). CONCLUSIONS:
      Adenoid cystic carcinomas of the breast have very favorable biologic
      characteristics and, consistent with this, an excellent prognosis. Good local
      control can be achieved by lumpectomy with radiation or by simple mastectomy.
      Axillary lymph node dissection is not helpful in clinical management.

PMID- 12001108
TI  - Male breast carcinoma in Israel: higher incident but possibly prognosis in
      Ashkenazi Jews.
AB  - BACKGROUND: Little information is available regarding male breast carcinoma.
      However, cumulative data have suggested a propensity for the disease among
      Ashkenazi Jews. Because Ashkenazi Jews comprise one of the major ethnic groups in
      Israel, the authors conducted a local study to shed more light on the features of
      this rare disease. METHODS: From 1960 to 2000, 131 men with breast carcinoma were
      treated at the Rabin Medical Center or the Rambam Medical Center, and, from 1980
      to 1997, 470 patients with this diagnosis were recorded in the Israel Cancer
      Registry. These two data bases were used to analyze the epidemiologic and
      clinicopathologic characteristics of male breast carcinoma in Israel. RESULTS:
      Seventy-eight percent of the 131 Jewish patients were Ashkenazi. Most of their
      clinical characteristics were similar to those of their Sephardic counterparts.
      However, there was a statistically significant difference in the pattern of
      comorbidity between these groups (P = 0.000), and there was a trend toward a
      younger age at onset and more advanced tumor stage at the time of diagnosis for
      the Sephardim. It also was found that Sephardic origin was associated with poorer
      outcome (P = 0.03). Analysis of the Cancer Registry data base revealed an 80%
      increase in the risk of the disease for Ashkenazi Jews compared with Sephardic
      Jews (odds ratio, 1.8; 95% confidence interval, 1.4-2.3; P = 0.001). Survival
      analysis from this source suggested a poorer outcome for Sephardic Jews compared
      with Ashkenazi Jews (62% vs. 64.3% estimated 5-year survival rates, respectively;
      P = 0.08). CONCLUSIONS: Analyses of two independent data bases, patient charts,
      and a cancer registry indicate that breast carcinoma seems to be more prevalent
      among Ashkenazi Jewish men. At the same time, affected Ashkenazi patients may
      have a more favorable outcome than their Sephardic counterparts.

PMID- 12001109
TI  - Breast ductal carcinoma in situ with microinvasion: a definition supported by a
      long-term study of 1248 serially sectioned ductal carcinomas.
AB  - BACKGROUND: The significance of microinvasion is still debated and clinical
      management is controversial. The authors defined ductal carcinoma in situ with
      microinvasion (DCIS-MI) as DCIS with infiltration of the periductal stroma by a
      few tumor cells, singly (type 1) or in clusters (type 2). With this definition,
      the authors attempted to evaluate the clinical significance of microinvasion.
      METHODS: The authors compared the clinical, pathologic features, and survival
      (median follow-up, 7.3 years) of 1248 patients with, respectively, DCIS (722
      patients), DCIS-MI with microinvasion type 1 and type 2 (243 patients), and
      invasive ductal carcinoma in situ with a predominant DCIS component greater than
      or equal to 80% of the tumor (IDC-DCIS, 283 patients). RESULTS: Microinvasion was
      associated with DCIS histologic type, grade, and extent (respectively, P < 10(
      8), P < 10(-3), P < 10(-4)). Axillary lymph node metastases were observed in a
      few patients with DCIS and DCIS-MI type 1 (respectively, 1.4% and none), in 10.1%
      with DCIS-MI type 2 and in 27.6% with IDC-DCIS. Metastasis free and overall
      survival probabilities were significantly different between three groups in the
      following order from best to worst prognosis: 1) the group comprising DCIS and
      DCIS-MI type 1, 2) the DCIS-MI type 2 group, and 3) the IDC-DCIS group.
      CONCLUSIONS: The authors' results suggest there are two types of DCIS-MI: 1) type
      1 that behaves like DCIS and should be managed as such; 2) type 2 that is less
      pejorative than IDC-DCIS but is more so than type 1.

PMID- 12001110
TI  - Influence of delay to diagnosis on prognostic indicators of screen-detected
      breast carcinoma.
AB  - BACKGROUND: Although delay to diagnosis after a breast screening abnormality
      causes anxiety, its effect on prognosis is unknown. METHODS: Using pooled data
      from five Canadian organized breast cancer screening programs, the authors used
      unconditional logistic regression to evaluate the effect of delay to diagnosis on
      prognostic indicators among 4465 women with invasive breast carcinoma diagnosed
      in the ipsilateral breast within 3 years of an abnormal screen performed during
      1990-1996. RESULTS: Women with high-suspicion screens (n = 1569) compared with
      those without (n = 2896) were more promptly investigated (median days from screen
      to diagnosis, 31 vs. 47; P < or = 0.0001), had larger tumors (79.4% vs. 55.9% >
      10 mm; P < or = 0.0001), and were more likely to be lymph node positive (33.9%
      vs. 17.3%; P < or = 0.0001). For delays beyond > 12 to < or = 20 weeks, a linear
      trend of increased tumor size and lymph node positivity began to emerge.
      Controlling for suspicion, the authors found that odds ratios for tumor size
      greater than 10 mm were 0.9 (95% CI, 0.66-1.17), 1.2 (95% confidence interval
      [CI], 0.88-1.56), 1.5 (95% CI, 1.05-2.16), and 2.1 (95% CI, 1.15-3.86) for delays
      of > 12 to < or = 20, > 20 to < or = 52, > 52 to < or = 104, and > 104 < or = 156
      weeks, respectively (p(trend) < or = 0.0001), compared with delays of > 4 to < or
      = 12 weeks. Similarly, odds ratios for lymph node metastasis were 1.0 (95% CI,
      0.67-1.42), 1.2 (95% CI, 0.84-1.69), 2.2 (95% CI, 1.48-3.15), and 3.2 (95% CI,
      1.84-5.55) for the same time intervals (p(trend) = 0.0033). CONCLUSIONS: The
      authors' findings suggest that delays to diagnosis of asymptomatic breast
      carcinoma of 6 to 12 months are associated with progression of breast carcinoma
      as measured by increasing risk of lymph node metastases and larger tumor size. A
      policy of early recall rather than biopsy for low suspicion mammographic
      abnormalities may introduce delays of this magnitude. The tendency to more
      expediently investigate women with high-suspicion, worse prognosis screens
      (suspicion bias) obscures whether delays shorter than 20 weeks also worsen
      prognostic indicators. Suspicion bias should be considered when interpreting the
      effect of delay on prognosis.

PMID- 12001111
TI  - Correlation between MIB-1 and other proliferation markers: clinical implications
      of the MIB-1 cutoff value.
AB  - BACKGROUND: Cell proliferation is a major determinant of the biologic behavior of
      breast carcinoma. MIB-1 monoclonal antibody is a promising tool for determining
      cell proliferation on routine histologic material. The objectives of this study
      were to compare MIB-1 evaluation to other methods of measuring cell
      proliferation, with a view to refining the cutoff used to classify tumors with
      low and high proliferation rates in therapeutic trials. METHODS: One hundred
      eighty-five invasive breast carcinomas were evaluated for cell proliferation by
      determining monoclonal antibody MIB-1 staining, histologic parameters (Scarff
      Bloom-Richardson grade and mitotic index) on paraffin sections, S-phase fraction
      (SPF) by flow cytometry, and thymidine-kinase (TK) content of frozen samples.
      RESULTS: There was a high correlation (P = 0.0001) between the percentage of MIB
      1 positive tumor cells and SPF, TK, histologic grade, and the mitotic index.
      Multivariate analyses including MIB-1 at 5 different cutoffs (10%, 15%, 17%
      [median], 20%, 25%) and the other proliferative markers showed that the optimal
      MIB-1 cutoff was 25% and that the mitotic index was the proliferative variable
      that best discriminated between low and high MIB-1 samples. A MIB-1 cutoff of 25%
      adequately identified highly proliferative tumors. Conversely, with a MIB-1
      cutoff of 10%, few tumors with low proliferation were misclassified. CONCLUSIONS:
      The choice of MIB-1 cutoff depends on the following clinical objective: if MIB-1
      is used to exclude patients with slowly proliferating tumors from
      chemotherapeutic protocols, a cutoff of 10% will help to avoid overtreatment. In
      contrast, if MIB-1 is used to identify patients sensitive to chemotherapy
      protocols, it is preferable to set the cutoff at 25%. The MIB-1 index should be
      combined with some other routinely used proliferative markers, such as the
      mitotic index.

PMID- 12001112
TI  - Increased mammography use and its impact on earlier breast cancer detection in
      Vermont, 1975-1999.
AB  - BACKGROUND: A trend toward earlier breast carcinoma detection in the United
      States has been attributed to screening mammography, although direct evidence
      linking this trend to the increased use of mammography in a general population is
      lacking. This study examined the effects of mammography on tumor size and
      axillary lymph node metastasis in Vermont over 25 years. METHODS: Pathology and
      mammography data from 3499 Vermont women who were diagnosed with invasive breast
      carcinoma during 1975-1984, 1989-1990, and 1995-1999 were compared. Logistic
      regression analysis was used to estimate the effects of age, mammography use, and
      period on the odds of a tumor < or = 2 cm and the odds of negative lymph nodes.
      RESULTS: The proportion of breast tumors that were detected by screening
      mammography increased from 2% during 1974-1984 to 36% during 1995-1999 (P <
      0.001), and these tumors were more likely to measure < or = 2 cm than tumors that
      were detected by other methods. Among women age > 50 years, the odds ratio (OR)
      was 4.5, with a 95% confidence interval (95% CI) of 3.5-6.4. The effect was
      smaller in younger women (OR, 1.8; 95% CI, 1.1-3.0). Mammographic detection
      increased the odds of negative lymph nodes by a similar amount in both age
      groups, although women age > 50 years were more likely to have negative lymph
      nodes than younger women (OR, 1.3; 95% CI, 1.1-1.6). Tumor size and lymph node
      metastasis also were related to the number of mammograms and to the mammographic
      interval. CONCLUSIONS: Most of the trend toward earlier detection in Vermont was
      due to mammography. Mammography had a lesser effect on tumor size among younger
      women, which may be related to less frequent screening, although its effect on
      lymph node metastasis was not age dependent. Women age < 50 years were more
      likely to have positive lymph nodes, independent of the method of detection or
      the frequency of mammography.

PMID- 12001113
TI  - HER2 status in patients with breast carcinoma is not modified selectively by
      preoperative chemotherapy and is stable during the metastatic process.
AB  - BACKGROUND: The objective of this study was to determine whether HER2 expression
      levels in breast carcinomas were modified by chemotherapy or during the
      metastatic process. METHODS: HER2 expression was analyzed on sequential tissue
      specimens taken from the primary tumor before patients received preoperative
      chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site.
      The first group of patients included 59 women who presented with T2-T4,N1-N2
      breast carcinoma and were treated by preoperative anthracycline-based CT and then
      underwent surgery. The second group included 44 patients with metastatic breast
      carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2
      status was determined by immunohistochemistry using an anti-p185(HER/neu)
      monoclonal antibody and was classified as overexpressed or not overexpressed.
      RESULTS: Among the patients who received preoperative CT, HER2 overexpression was
      observed in 15 of 59 patients (25%). A complete pathologic response was observed
      in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining
      residual tumors and was no longer detectable in 2 tumors. In addition, the 29
      tumors with no HER2 overexpression before CT remained negative after treatment.
      In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44
      primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained
      in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two
      patients who had low levels of HER2 overexpression in their primary tumors, no
      staining was observed in the secondary tumor (one pulmonary tumor and one liver
      tumor). There were no tumors in which the overexpression of HER2 was found only
      in the metastasis. CONCLUSIONS: The current study showed that, in most patients,
      HER2 overexpression was unchanged after CT and in metastatic sites. No HER2
      negative primary tumors became HER2 positive after patients received CT or during
      the metastatic process. In a few patients, a diminution in the level of HER2
      expression was observed after CT or in secondary tumors. This may have been due
      to a transitory state of altered tumor cells or to the selection of HER2 negative
      tumor cells clones.

PMID- 12001114
TI  - Phase II trial of irinotecan in combination with amifostine in patients with
      advanced colorectal carcinoma.
AB  - BACKGROUND: Irinotecan is effective in patients with advanced colorectal
      carcinoma in both first-line and salvage settings but its use can be limited by
      serious side effects. Amifostine has been shown to reduce the incidence of
      cisplatin-induced cumulative renal toxicity in patients with advanced ovarian
      carcinoma and nonsmall cell lung carcinoma. In the current pilot Phase II trial,
      the authors examined the potential role of amifostine as a protective agent
      against irinotecan-induced diarrhea and myelosuppression and evaluated an every-2
      weeks regimen as an alternative schedule for the administration of irinotecan in
      patients with previously treated metastatic colorectal carcinoma. METHODS: All
      patients received amifostine, 740 mg/m2, followed by irinotecan, 250 mg/m2, every
      2 weeks. A 6-week cycle of chemotherapy (every 2 weeks for 3 treatments) was
      chosen to assess toxicity and response. The main objective of the current study
      was to evaluate the impact of amifostine on gastrointestinal and hematologic
      toxicity. RESULTS: A total of 22 patients entered the current study. Six of these
      22 patients (27%) had WHO Common Toxicity Criteria Grade 3 or 4 diarrhea,
      including 2 patients (9%) with Grade 4 diarrhea. Eight of 22 patients (36.3%)
      developed Grade 3 or 4 neutropenia (Grade 4 in 4 of the 22 patients [18%]). Dose
      reduction was required in 25% of the treatment cycles. Five of the 22 patients
      (23%) withdrew from the trial due to amifostine toxicity. Of the 15 patients who
      were evaluable for response, 4 patients (26.6%) had achieved a partial response
      and 9 (60%) had stable disease as their best response. CONCLUSIONS: The
      combination of irinotecan with amifostine in patients with previously treated
      metastatic colorectal carcinoma did not appear to reduce irinotecan toxicity.
      Amifostine did not appear to interfere with the cytotoxic effect of irinotecan.
      The results of the current study did demonstrate efficacy and safety of the every
      2-weeks irinotecan schedule that was comparable to other established regimens and
      these results support its feasibility as a reasonable alternative in this disease
      setting.

PMID- 12001115
TI  - pT1 clear cell renal cell carcinoma: a study of the association between MIB-1
      proliferative activity and pathologic features and cancer specific survival.
AB  - BACKGROUND: The majority of patients with pT1 clear cell renal cell carcinoma
      (RCC) are cured with nephrectomy. However, a few patients will die of RCC. In
      several studies, MIB-1 proliferative activity was identified as an independent
      predictor of survival in patients with RCC. The objective of the current study
      was to examine MIB-1 proliferative activity in a large series of patients with
      pT1 clear cell RCC who were treated uniformly with radical nephrectomy, and to
      examine the association between proliferative activity and cancer specific
      survival in a multivariate model incorporating tumor size, nuclear grade, and
      tumor necrosis. METHODS: Patients with solitary pT1 clear cell RCC who underwent
      radical nephrectomy between 1970-1997 were eligible for the current study. For
      each of the 40 patients who died of RCC, a stratified random sample of at least 3
      year-matched patients who still were alive or had died of other causes at the
      time of last follow-up was selected. Patient age at nephrectomy, patient gender,
      tumor size, nuclear grade, and tumor necrosis were evaluated, and the MIB-1
      proliferative activity was assessed using digital image analysis. Univariate and
      multivariate Cox proportional hazards models were fit to assess the features
      associated with cancer specific survival. The associations between MIB-1
      proliferative activity and pathologic features were assessed using the Wilcoxon
      rank sum test. RESULTS: The mean MIB-1 value for those patients who died of clear
      cell RCC was 6.5% compared with 3.6% for those patients who died of other causes
      or were still alive at the time of last follow-up. Patients whose tumor had an
      MIB-1 proliferative activity > o r = 5.0% were more than twice as likely to die
      of RCC than patients whose tumors had a MIB-1 activity < 5% (P = 0.02). However,
      after adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative
      activity was not found to be associated significantly with cancer specific
      survival. There was a significant association between MIB-1 proliferative
      activity and tumor size, nuclear grade, and necrosis. CONCLUSIONS: After
      adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative
      activity was not found to be an independent predictor of outcome in patients with
      pT1 clear cell RCC who were treated with radical nephrectomy. There was a
      significant association between MIB-1 and other well established pathologic
      prognostic features of pT1 clear cell RCC.

PMID- 12001116
TI  - Loss of PTEN expression is associated with metastatic disease in patients with
      endometrial carcinoma.
AB  - BACKGROUND: The PTEN tumor suppressor gene frequently is involved in endometrial
      carcinoma. Loss of heterozygosity and mutations reportedly are common, although
      the biologic importance of these changes remain largely unknown. The objective of
      this study was to assess the pattern of PTEN expression by immunohistochemistry
      in a large series of patients with endometrial carcinoma. METHODS: A population
      based series of 316 patients with endometrial carcinoma who had long and complete
      follow-up was investigated for PTEN expression and its correlation with
      clinicopathologic variables, tumor markers, and survival. RESULTS: PTEN protein
      expression was mainly cytoplasmic in tumor cells, with no expression seen in 56
      of 279 patients (20%) who had evaluable results. A heterogeneous staining pattern
      was found in 70 tumors (25%). A significant association between the loss of PTEN
      expression and metastatic disease was identified (P = 0.05). However, PTEN
      staining did not influence survival significantly. CONCLUSIONS: The loss of PTEN
      expression is relatively frequent in endometrial carcinoma and is associated
      significantly with metastatic disease. This indicates that the PTEN system plays
      an important role in some endometrial carcinomas, but further studies of PTEN
      protein expression related to various genetic alterations are necessary.

PMID- 12001117
TI  - Fertility-preserving treatment in young patients with endometrial adenocarcinoma.
AB  - BACKGROUND: Hormone therapy alone for early-stage, low-grade endometrial
      carcinoma arising in young women has been reported occasionally in case reports
      or small series. However, a comprehensive guideline for selection, treatment, and
      follow-up is not available as yet. METHODS: In the current study, the authors'
      evaluated the outcome of a cohort of young women with clinically diagnosed
      endometrial adenocarcinoma Stage IA, Grade 1 who were selected for fertility
      preserving treatment by stringent staging procedures and treated in a standard
      protocol using combinations of megestrol acetate, tamoxifen, and gonadotropin
      releasing hormone analog (GnRHa). RESULTS: Nine eligible patients were treated
      between 1991 and 1999. The median age of the patients was 32 years (range, 30-39
      years). Of the 9 patients, 8 (88.9%) achieved complete remission after hormone
      therapy. Four patients had ever conceived (two patients had three term
      pregnancies and underwent consolidation hysterectomy after completion of family
      planning). Only one patient underwent hysterectomy for failure to respond, whose
      tumor was estrogen receptor (ER)/progesterone receptor (PgR) positive by
      immunostaining but negative by ligand-binding method. Another patient, whose
      tumor was ER negative/PgR positive, had residual carcinoma on the first
      assessment and achieved complete remission after replacement of tamoxifen with a
      GnRHa. Four responders later developed recurrent endometrial carcinoma. One
      underwent immediate hysterectomy. Two were successfully re-treated with hormone
      therapy, but the other did not respond and underwent hysterectomy. All nine
      patients have been alive without evidence of disease 25-113 (median, 69) months
      from initial diagnosis. CONCLUSIONS: The treatment strategy described in the
      current study is feasible. A larger multicenter trial of fertility-preserving
      treatment is warranted for nulliparous young patients with well selected Stage I,
      Grade 1, endometrial adenocarcinoma.

PMID- 12001118
TI  - Quantitation of human papillomavirus 16 E6 and E7 DNA and RNA in residual
      material from ThinPrep Papanicolaou tests using real-time polymerase chain
      reaction analysis.
AB  - BACKGROUND: The detection of specific human papillomavirus 16 (HPV-16) E6 and E7
      oncogene transcripts may be a sensitive indicator of the direct involvement of
      viral oncogenes in the development of cervical neoplasia and carcinoma. The goal
      of this study was to determine the potential clinical uses of real-time
      polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) methods
      for evaluating HPV-16 E6 and E7 oncogene expression. METHODS: ThinPrep cervical
      samples were tested for expression of oncogenes of HPV-16 by real-time PCR or RT
      PCR analysis and were compared with detection of expression by conventional PCR
      and RT-PCR analysis. Both sets of results were correlated with the cytologic
      diagnosis of the cervical samples. RESULTS: The presence of HPV-16 E6 and E7 DNA
      and RNA was observed only in HPV-16 positive cervical carcinoma cell lines but
      not in HPV-18 positive or HPV negative cell lines. The percentage positive for
      HPV-16 E6 or E7 DNA in a series of ThinPrep cervical cytologic samples (n = 348
      samples) was 0% for negative samples (n = 45 samples), 9.7% for atypical squamous
      cells of undetermined significance (ASCUS; n = 144 samples), 16.9% for low-grade
      squamous intraepithelial lesion (LSIL; n = 118 samples), and 51.2% for high-grade
      intraepithelial lesion (HSIL; n = 41 samples). The copy numbers per nanogram for
      both DNA and RNA E6 and E7 were increased significantly as severity of the
      lesions progressed from ASCUS to HSIL, and RNA copy numbers were a more sensitive
      indicator of HPV-16 E6 and E7 expression than DNA copy numbers. The increase in
      copy numbers took place in a stepwise fashion from ASCUS, to LSIL, to HSIL.
      CONCLUSIONS: The detection of HPV-16 E6 and E7 expression by real-time RT-PCR or
      PCR analysis in ThinPrep cervical cytologic specimens may serve as a quick,
      reliable, and sensitive tool to identify a subset of patients who express HPV-16
      oncoproteins.

PMID- 12001119
TI  - Expression of estrogen receptor, progesterone receptor, and insulin-like growth
      factor receptor-1 and of MIB-1 in patients with recurrent pleomorphic adenoma of
      the parotid gland.
AB  - BACKGROUND: Patients with recurrent pleomorphic adenomas of the parotid gland are
      difficult to manage without considerable risk of facial nerve injury. The
      prognostic significance of progesterone receptor (PR) and estrogen receptor (ER)
      reported in these adenomas was evaluated in patients with recurrent pleomorphic
      adenomas, comparing the results in a group of patients with primary adenomas
      without recurrences during 10 years of follow-up. METHODS: Paraffin embedded
      tumor samples from 52 patients with recurrent pleomorphic adenoma of the parotid
      gland were collected and stained immunohistochemically. Expression of PR, ER, Ki
      67 antigen, and insulin-like growth factor receptor-1 (IGFR-1) was analyzed in
      resected samples of recurrent tumors and was compared with samples from a control
      group of patients with primary pleomorphic adenoma. RESULTS: A difference (P <
      0.05) in the type of tumor was observed between the recurrent group (more cell
      poor variants) and the control group. ER expression was low in both groups (19%
      and 17%, respectively), but immunoreactivity for ER was higher (48%) in normal
      parotid gland tissue. PR expression in the recurrent group (96%) was higher
      compared with PR expression in the control group (61%; P < 0.001). PR expression
      and IGFR-1 expression were correlated weakly (correlation coefficient = 0.660; P
      = 0.053) in the recurrent group. The expression of growth fraction (Ki-67 score)
      and IGFR-1 was similar in both groups but was more extensive compared with normal
      parotid gland tissue. CONCLUSIONS: PR seems to be a prognostic factor in
      recurrent pleomorphic adenoma of the parotid gland. The PR pathway can be
      considered a potential target for hormone treatment in patients with these
      recurrent adenomas.

PMID- 12001120
TI  - A prospective, randomized trial comparing neoadjuvant chemotherapy with
      radiotherapy alone in patients with advanced nasopharyngeal carcinoma.
AB  - BACKGROUND: A prospective, randomized study was performed to determine the
      efficacy of neoadjuvant chemotherapy over radiotherapy alone in patients with
      locally advanced nasopharyngeal carcinoma. METHODS: From January 1991 to December
      1998, 80 patients were enrolled in this study. Patients with locoregional
      carcinoma of the nasopharynx were randomized to receive two courses of
      chemotherapy, consisting of cisplatin and 5-fluorouracil (CDDP-5FU), that were
      administered before radiation therapy (CT arm) or radiotherapy alone. The
      patients who received neoadjuvant chemotherapy were treated with radiation
      therapy, which was scheduled to commence 2 weeks after the second course
      chemotherapy. RESULTS: With a median follow-up of 49 months, a trend toward
      improved overall survival or disease free survival favoring the CT arm was
      observed (5-year overall survival rate, 60% vs. 48%; 5-year disease free survival
      rate, 55% vs. 43%), although this difference was not significant. There were no
      differences in locoregional failure free survival between the two arms. However,
      metastasis free survival favored the CT arm, although this difference was not
      significant. The results also demonstrated that most patients in the CT arm who
      experienced recurrent disease developed locoregional recurrences before distant
      metastases, suggesting that improvements in locoregional control may lead to
      improved disease free survival. CONCLUSIONS: The use of CDDP-5FU chemotherapy
      prior to radiotherapy in patients with nasopharyngeal carcinoma did not result in
      a significant improvement in disease free survival or overall survival. However,
      there was a positive tendency in favor of the CT arm for distant metastasis free
      survival, although there was no improvement in the locoregional recurrence free
      survival rate.

PMID- 12001121
TI  - Phase II study of methotrexate, vinblastine, doxorubicin, and cisplatin in
      patients with squamous cell carcinoma of the upper respiratory or alimentary
      passages of the head and neck.
AB  - BACKGROUND: The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and
      cisplatin have shown activity in patients with recurrent or metastatic squamous
      cell carcinoma arising from the upper respiratory or alimentary passages of the
      head and neck. This study was undertaken to assess the antitumor activity and
      toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin,
      and cisplatin (MVAC) in this patient population. METHODS: Patients with
      histologically confirmed unresectable, recurrent, or metastatic squamous cell
      carcinoma arising from the upper respiratory or alimentary passages of the head
      and neck were treated with MVAC over a 4-week cycle. The doses were as follows:
      30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2,
      15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2.
      The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment
      was discontinued after four cycles for those whose disease remained stable.
      Patients were evaluated for chemotherapy response, progression free survival, and
      survival. RESULTS: Thirty-six patients were accrued onto this study between April
      1993 and February 1996. One patient (3%) with a history of cardiac heart failure
      was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was
      observed in 55% of the patients during the first cycle of treatment and in 81% of
      the patients during the entire course of their treatment. The overall objective
      response rate over the first 4 cycles of treatment was 46% (90% confidence
      interval [CI], 33-60%). Two of the 18 patients who responded had a complete
      response. The median time to progression was 19 weeks, and 1-year progression
      free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and
      the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with
      unresected residual or recurrent disease, the median time to progression was 11
      weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and
      median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21
      63%). Among the 13 patients with metastatic disease, the median time to
      progression was 26 weeks, and the 1-year progression free survival rate was 23%
      (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate
      was 54% (95% CI, 33-89%). CONCLUSIONS: Methotrexate, vinblastine, doxorubicin,
      and cisplatin is an active chemotherapy regimen in patients with recurrent or
      metastatic squamous cell cancer arising from the upper respiratory or alimentary
      passages of the head and neck.

PMID- 12001122
TI  - Clinical significance of telomerase activity in multiple myeloma.
AB  - BACKGROUND: The clinical course of patients with multiple myeloma varies, and
      therefore it is important to evaluate the disease state. We studied the
      telomerase activity of myeloma cells as a possible prognostic factor in such
      patients. METHODS: Twenty five samples from patients with multiple myeloma were
      studied. We purified myeloma cells in bone marrow samples according to the
      expression of surface antigens, CD38 and CD45. CD38+/CD45- or dim cells had
      morphologic characteristics of myeloma cells, with a purity exceeding 95%. The
      telomerase activity of myeloma cells was determined by a polymerase chain
      reaction-based telomeric repeat amplification protocol assay. Ki-67 positivity of
      the purified cells was determined by flow cytometry using anti-Ki-67 antibody.
      The relationship between telomerase activity and prognostic factors was also
      examined. RESULTS: A significantly high degree of telomerase activity was
      detected in subjects with a serum beta2-microglobulin level > or = 6 mg/dL or at
      Stage III (P = 0.002). The serum C-reactive protein, lactate dehydrogenase, and
      creatinine levels did not correlate with the telomerase activity, but this
      activity did significantly correlate with Ki-67 positivity and the percentage of
      plasma cells in the bone marrow (r = 0.561, P = 0.004, and r = 0.397, P = 0.049,
      respectively). The patients with high levels of telomerase activity were thus
      found to have a significantly short survival time after sampling (P = 0.035).
      CONCLUSIONS: The measurement of the telomerase activity in myeloma cells was
      found to be a reliable marker for the proliferating capacity and tumor mass in
      myeloma patients. The telomerase activity of myeloma cells may therefore be
      useful as a prognostic factor.

PMID- 12001123
TI  - Topoisomerase IIalpha gene expression is regulated by the p53 tumor suppressor
      gene in nonsmall cell lung carcinoma patients.
AB  - BACKGROUND: Topoisomerase IIalpha (Topo IIalpha) is an essential nuclear enzyme
      for chromosome segregation during mitosis. Previous experimental studies using
      cell lines reported that Topo IIalpha expression was negatively regulated by wild
      type p53 through the gene's promoter region. METHODS: Surgically resected tumor
      specimens from 98 nonsmall cell lung carcinoma (NSCLC) patients who were not
      treated with preoperative chemotherapy were studied. Quantitative reverse
      transcription polymerase chain reaction analysis was done to evaluate Topo
      IIalpha gene expression. Polymerase chain reaction single strand conformation
      polymorphism following sequencing was performed to investigate mutations of p53.
      RESULTS: Topo IIalpha gene expression in squamous cell carcinomas was
      significantly higher than in adenocarcinomas (P = 0.0007). Topo IIalpha gene
      expression in moderately differentiated tumors and poorly differentiated tumors
      was significantly higher than in well differentiated tumors (P = 0.0032 and P =
      0.0005, respectively). Thirty nine tumors (40%) had mutations of p53. Topo
      IIalpha gene expression in tumors with mutant p53 was significantly higher than
      in those with wild-type p53 (P = 0.0224). CONCLUSIONS: The current study suggests
      that Topo IIalpha gene expression is regulated by p53 gene status in NSCLC
      patients and that the overexpression of Topo IIalpha induced by mutant p53 might
      cause more aggressive carcinogenesis.

PMID- 12001124
TI  - Multiple primary melanoma revisited.
AB  - BACKGROUND: Incidence of cutaneous melanoma continues to increase in the
      Caucasian population worldwide. Approximately 5% of melanoma patients develop
      additional primary melanoma. This rate is significantly higher than the estimated
      lifetime risk of an individual for developing the disease (1.4%). These features
      suggest that a genetic predisposition may underlie multiple primary melanomas
      (MPMs). Prior studies had identified CDKN2A mutations in a few MPM individuals.
      The objectives of this study were to determine the frequency of family history of
      melanoma in MPM cases, to characterize other clinical features including history
      of other cancer, and to determine the association with functional CDKN2A
      mutations. METHODS: This study used a case series design. All living patients who
      had been seen in the Pigmented Lesion Clinic at the University of Pennsylvania
      and who had more than one primary invasive malignant melanoma or an invasive
      primary followed by an in situ melanoma were eligible for participation. RESULTS:
      Individuals with MPM frequently had a family history of melanoma, dysplastic nevi
      (DN), and/or another cancer including basal cell carcinoma (BCC), and squamous
      cell carcinoma breast cancer, and a personal history of DN, and basal cell
      carcinoma. Germline mutations in CDKN2A gene were identified in 8 of 96 MPM cases
      (8.3%, 95% confidence interval, 6.7-9.9%). CONCLUSIONS: These data indicate that
      the presence of MPM is associated with a modest incidence of a family history of
      melanoma, DN, or BCC and a small association with CDKN2A mutations. Therefore, in
      addition to the MPM index case, other family members can benefit from screening
      and regular surveillance for melanoma, DN, and BCC.

PMID- 12001125
TI  - Soft tissue sarcoma of the upper extremity: a 5-year experience at two
      institutions emphasizing the role of soft tissue flap reconstruction.
AB  - BACKGROUND: The objective of this study was to define the impact of soft tissue
      flap reconstruction on multimodality therapy for patients with soft tissue
      sarcomas of the upper extremity. Treatment standards continue to evolve for these
      patients, and, with multimodality therapy, most of them are candidates for limb
      preserving surgery. Consequently, the role of soft tissue flap reconstruction is
      expanding. METHODS: A review was conducted of 100 consecutive patients with soft
      tissue sarcomas of the upper extremity who underwent surgery at several
      institutions between 1992 and 1997. RESULTS: Seventy-one patients underwent
      direct closure of defects after tumor resection, and 29 patients required soft
      tissue reconstruction with flaps. These groups were similar in most respects,
      except that 52% of the patients who required soft tissue reconstruction presented
      with recurrent disease (P = 0.0004), and 79% of them had tumors measuring > 5 cm
      in greatest dimension (P = 0.0003). The patients who required flap reconstruction
      had larger skin deficits after undergoing tumor resection (140 cm2) compared with
      the patients who had wounds that were managed by direct closure (40 cm2; P <
      0.00001). Margins around the resected tumors were larger (1.62 cm) when flaps
      were employed compared with margins when defects were closed directly (0.87 cm; P
      = 0.0005). However, the number of patients with intralesional, marginal, wide,
      and radical resections was the same regardless of wound management. Major
      complications occurred in 14% of patients, but none led to death or amputation.
      The median follow-up was 31 months, and 66% of patients had no evidence of
      disease at that time. Rates of local recurrence and survival were similar for
      patients who underwent flap reconstruction compared with patients who underwent
      direct closure. CONCLUSIONS: Soft tissue flap reconstruction facilitates therapy
      for patients with soft tissue sarcomas of the upper extremity, so that patients
      with larger tumors can undergo resection, limiting complications and limb
      sacrifice.

PMID- 12001126
TI  - Survival by radiation therapy oncology group recursive partitioning analysis
      class and treatment modality in patients with brain metastases from malignant
      melanoma: a retrospective study.
AB  - BACKGROUND: In a population of patients with brain metastases from melanoma, the
      authors sought to determine whether various therapies provided any benefit at
      all, whether local therapy was better than whole brain radiotherapy (WBRT), and
      whether combined local therapy and WBRT provided any advantage over local therapy
      alone. They also analyzed survival according to a Radiation Therapy Oncology
      Group (RTOG) recursive partitioning analysis (RPA) to determine how well the RTOG
      RPA classes predicted survival in this patient population and whether treatments
      varied in effectiveness from category to category. METHODS: A total of 74
      patients with brain metastases from melanoma were treated at The Cleveland Clinic
      Foundation between 1984 and 1998. For this study, the authors reviewed patient
      charts and confirmed survival status. Survival was compared by treatment modality
      (surgical resection, WBRT, stereotactic radiosurgery, or WBRT combined with local
      therapy). Survival also was compared according to the RTOG RPA prognostic classes
      (Class 1, Class 2, or Class 3), which has not been validated previously in
      patients with malignant melanoma. RESULTS: The median survival was 5.5 months for
      all patients. Survival varied significantly by RTOG prognostic class; The median
      survival was 10.5 months (range, 2.2-99.2 months) for patients in Class 1, 5.9
      months (range, 0.2-43.9 months) for patients in Class 2, and 1.8 months (range,
      0.1-6.9 months) for patients in Class 3 (P < 0.0001). Survival analysis showed
      that combined treatment offered significantly better survival (P < 0.0001;
      combined vs. other). The median survival was 8.8 months (range, 1.8-99.2 months)
      for the combined therapy group, 4.8 months (range, 1.2-27.8 months) for the local
      therapy alone group, 2.3 months (range, 0.2-9.6 months) for the WBRT alone group,
      and 1.1 months (0.1-3.0 months) for the group that received no therapy.
      CONCLUSIONS: Adding WBRT to local therapy may improve survival in this group of
      patients: Combined therapy was superior to WBRT alone. The RPA classification
      scheme likely has prognostic value for patients with brain metastases from
      malignant melanoma. Prospective studies are required to overcome selection bias
      and confirm these results.

PMID- 12001127
TI  - Prognostic relevance of cell biologic and biochemical features in conventional
      chondrosarcomas.
AB  - BACKGROUND: Conventional chondrosarcoma is the second most common malignant solid
      tumor of bone, and its management still poses a challenge for the orthopedic
      surgeon. Currently, tumor grade is the only parameter of prognostic significance
      besides stage and, possibly, resection margins. Additional independent prognostic
      markers therefore would be highly valuable for patient management. METHODS: In
      the current study, the authors evaluated biologic markers for various
      chondrocytic phenotypes by histochemical and immunohistochemical technology in a
      large series of clinically well defined cases of enchondromas and conventional
      chondrosarcomas, each with at least 5 years of clinical follow-up. RESULTS: The
      authors' results confirm the strong correlation between clinical behavior and
      cell differentiation as expressed by marker genes. The phenotypes of the tumor
      cells are the biologic substrate of the histopathologic appearance of the
      neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types
      II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic
      phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and
      long survival. Conversely, collagen Type I, together with cell spindling,
      indicates a transition to a more proliferative, so-called "dedifferentiated"
      phenotype, which clearly is associated with a poorer prognosis. The changes in
      cellular phenotypes are accompanied by changes in proliferative activity. Thus,
      low-grade neoplasms showing mainly mature and terminally differentiated
      (hypertrophic) chondrocytes display only scant proliferation whereas less
      differentiated chondrosarcomas with biologically dedifferentiated chondrocytes
      show significantly higher proliferative activity, a feature that is also highly
      correlated with prognosis. CONCLUSIONS: These data indicate that molecular
      markers are to a large extent the biologic basis of the conventional grading,
      rather than representing independent prognostic markers. The authors' results
      further indicate that COL1 has significant value in the distinction between
      enchondromas and low-grade chondrosarcomas including these that are
      histologically similar. Further understanding of chondrocytic phenotypes will be
      a promising way to provide new tumor markers for better understanding, diagnosis,
      and treatment of chondroid neoplasms.

PMID- 12001128
TI  - Gleason scores of prostate biopsy and radical prostatectomy specimens over the
      past 10 years: is there evidence for systematic upgrading?
AB  - BACKGROUND: With the advent of the prostate specific antigen (PSA) assay, an
      increased detection rate of prostate carcinoma has ensued. This has been
      associated with a downward stage migration. In contrast, grade has shifted
      heavily toward moderate differentiation. The authors sought to test the
      hypothesis that such changes in grade in part may be because of trends among
      pathologists to upgrade similar specimens over time. METHODS: Two expert
      genitourinary pathologists regraded 23 prostate biopsies and 15 radical
      prostatectomy specimens during a 3-year period (1989-1991). Each pathologist then
      regraded 32 prostate biopsies and 15 radical prostatectomies from 1998 to 2000.
      For both time periods, each pathologist regraded only specimens that they
      personally had graded initially. All specimens were scored using the Gleason
      system, the predominant system used in describing prostate carcinoma grade. In
      evaluating original and regraded scores, the authors classified score changes
      between less than or equal to 6 and greater than or equal to 7 or between 7 and
      greater than or equal to 8 as significant because such changes have a high
      probability of altering clinical management. The results were analyzed using the
      two-tailed Fisher exact test. RESULTS: Of 23 prostate biopsies from 1989 to 1991,
      10 of 23 (44%) had a clinically significant Gleason score change when regraded,
      whereas 2 of 15 (13%) radical prostatectomy specimens from the same period had a
      clinically significant Gleason score change. A significant change in the
      distribution of biopsy Gleason scores on regrading was observed (P < 0.04). In
      comparison, when the prostate biopsies from 1998-2000 were regraded, 10 of 32
      (31%) had a clinically significant grade change. Radical prostatectomy specimens
      from the same period revealed 3 of 15 (20%) with a clinically significant grade
      change. After regrading the biopsies from 1989-1991, 8 of 23 (35%) of were
      upgraded, whereas 2 of 23 (9%) were downgraded. In comparison, of the biopsies
      with significant changes from 1998 to 2000, 3 of 32 (9%) were upgraded, whereas 7
      of 32 (22%) were downgraded. Of the radical prostatectomy specimens with
      significant change, only 2 of 15 from each period were upgraded. Significant
      upgrading (P < 0.005) occurred only in the biopsy specimens from 1989 to 1991.
      CONCLUSIONS: The authors' data suggest that rates of upgrading and downgrading of
      biopsy specimens differ between the 1989-1991 cases and the 1998-2000 cases, with
      the 1989-1991 samples exhibiting a significant change toward higher grades.
      Although not excluding the possibility of a change in the biology of prostate
      carcinoma over time, these findings suggest that the apparent trend toward higher
      biopsy grades in part may be because of how pathologists interpret these
      specimens today as compared with 10 years ago. Therefore, outcome studies
      including a biopsy Gleason score from older specimens as a risk variable have a
      significant chance of being vulnerable to this phenomenon. Based on the authors'
      data, all such specimens should undergo rereview.

PMID- 12001129
TI  - Malignant placental site trophoblastic tumor: a cytogenetic study using
      comparative genomic hybridization and chromosome in situ hybridization.
AB  - BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of
      gestational trophoblastic neoplasm composed predominantly of intermediate
      trophoblast. Most showed benign behavior whereas 10-15% of PSTTs were clinically
      malignant with later recurrence and metastasis. Currently, there are no reliable
      means to predict clinical outcome, and cytogenetic information is scanty.
      METHODS: The clinicopathologic features of two cases of malignant PSTT were
      analyzed. Cytogenetic analysis was performed by comparative genomic hybridization
      (CGH) and chromosome in situ hybridization (CISH) using frozen tissue and
      paraffin embedded sections, respectively. RESULTS: Both patients were 32 years
      old at time of diagnosis. One patient with PSTT presented with menorrhagia, and
      the other presented with symptoms of missed abortion. Elevated serum human
      chorionic gonadotropin (HCG) was detected in both patients. Histologic
      examination showed the typical features of PSTT with high mitotic count (> 5/10
      high-power fields). Ovarian and lung metastasis occurred in both patients.
      Immunohistochemical staining revealed an equal distribution of HCG and human
      placental lactogen. Cytogenetic studies by CISH showed that karyotypes of these
      two malignant PSTTs were diploid. Analysis of the tumor tissue by CGH did not
      show any changes in DNA copy numbers. CONCLUSIONS: The authors' study indicated
      that the two metastasizing PSTTs had balanced diploid karyotype. The malignant
      behavior of PSTTs may be not related to the DNA copy number changes. Such
      cytogenetic study may be useful in distinguishing metastatic PSTT from
      choriocarcinoma.

PMID- 12001130
TI  - Cancer pain management among underserved minority outpatients: perceived needs
      and barriers to optimal control.
AB  - BACKGROUND: Minority patients with cancer are at risk for undertreatment of
      cancer-related pain. Most studies of patient-related barriers to pain control
      have surveyed primarily non-Hispanic Caucasian patients. The purpose of the
      current study was to explore barriers to optimal pain management among African
      American and Hispanic patients with cancer through the use of structured patient
      interviews. Structured interviews allowed the authors to probe for previously
      unidentified barriers to pain management in these populations. METHODS: Thirty
      one socioeconomically disadvantaged minority patients with cancer (14 African
      American patients and 17 Hispanic patients) who had cancer-related pain completed
      structured interviews that assessed three main content areas: information and
      communication regarding cancer pain, treatment of cancer pain, and the meaning of
      cancer pain. RESULTS: The African-American and Hispanic patients reported severe
      pain and many concerns about pain management. The majority of patients in both
      ethnic groups expressed a belief in stoicism and concerns about possible
      addiction to opioid medications and the development of tolerance. The patients
      described their physicians as the most frequent and trusted source of information
      about cancer pain. However, patients also reported difficulties with
      communication and a reluctance to complain of pain. CONCLUSIONS: The reported
      barriers to pain management indicate that socioeconomically disadvantaged African
      American and Hispanic patients can benefit from educational interventions on
      cancer pain that dispel myths about opioids and teach patients to communicate
      assertively about their pain with their physicians and nurses.

PMID- 12001131
TI  - The New American Joint Committee on Cancer staging system for cutaneous melanoma:
      a critical analysis based on data of the German Central Malignant Melanoma
      Registry.

PMID- 12001132
TI  - A high number of tumor free axillary lymph nodes from patients with lymph node
      negative breast carcinoma is associated with poor outcome.

PMID- 12001133
TI  - Assessment of morphometric measurements of prostate carcinoma volume.

PMID- 12001134
TI  - Visual estimate of the percentage of carcinoma is an independent predictor of
      prostate carcinoma recurrence after radical prostatectomy.

PMID- 12001136
TI  - De novo establishment and cost-effectiveness of Papanicolaou cytology screening
      services in the Socialist Republic of Vietnam.

PMID- 12001138
TI  - Analysis of the recurrence in relation to the plannings target volume (PTV) for
      brachytherapy or external beam radiation therapy (EBRT).

PMID- 12001139
TI  - Expression of hypoxia-inducible factor-1alpha in oligodendrogliomas: its impact
      on prognosis and on neoangiogenesis.

PMID- 12001163
TI  - Metabolic engineering of Pseudomonas putida for the utilization of parathion as a
      carbon and energy source.
AB  - Pseudomonas putida KT2442 was engineered to use the organophosphate pesticide
      parathion, a compound similar to other organophosphate pesticides and chemical
      warfare agents, as a source of carbon and energy. The initial step in the
      engineered degradation pathway was parathion hydrolysis by organophosphate
      hydrolase (OPH) to p-nitrophenol (PNP) and diethyl thiophosphate, compounds that
      cannot be metabolized by P. putida KT2442. The gene encoding the native OPH
      (opd), with and without the secretory leader sequence, was cloned into broad-host
      range plasmids under the control of tac and taclac promoters. Expression of opd
      from the tac promoter resulted in high OPH activity, whereas expression from the
      taclac promoter resulted in low activity. A plasmid-harboring operons encoding
      enzymes for p-nitrophenol transformation to beta-ketoadipate was transformed into
      P. putida allowing the organism to use 0.5 mM PNP as a carbon and energy source.
      Transformation of P. putida with the plasmids harboring opd and the PNP operons
      allowed the organism to utilize 0.8 mM parathion as a source of carbon and
      energy. Degradation studies showed that parathion formed a separate dense, non
      aqueous phase liquid phase but was still bioavailable.

PMID- 12001164
TI  - Connection between gene dosage and protein stability revealed by a high-yield
      production of recombinant proteins in an E. coli LexA1(Ind-) background.
AB  - Bacterial production of a plasmid-encoded bacteriophage P22 tailspike protein
      shows different yield and impact on cell viability in RecA+ LexA+, RecA- LexA+
      and RecA+ LexA1(Ind-) backgrounds. In a LexA1(Ind-) context, we have observed
      lesser toxicity and higher productivity than in the wild-type strain, in which
      the bacterial growth was inhibited after induction of recombinant gene
      expression. Also, a negative effect of the incubation temperature on the growth
      of producing cells was also detected. By exploring the molecular basis of these
      inhibitory events, we found a connection between the dosage of the recombinant
      gene and the proteolytic stability of the encoded protein. Under both genetic and
      environmental conditions favoring higher plasmid copy number and consequently
      increasing the synthesis rate of the recombinant protein, enhanced protein
      degradation was observed in parallel with an important growth inhibition.
      Altogether, the obtained data suggest the existence of a critical concentration
      of recombinant protein over which cell proteolysis is stimulated at rates not
      compatible with optimal physiological conditions for bacterial growth.

PMID- 12001165
TI  - Sustained hydrogen photoproduction by Chlamydomonas reinhardtii: Effects of
      culture parameters.
AB  - The green alga, Chlamydomonas reinhardtii, is capable of sustained H(2)
      photoproduction when grown under sulfur-deprived conditions. This phenomenon is a
      result of the partial deactivation of photosynthetic O(2)-evolution activity in
      response to sulfur deprivation. At these reduced rates of water-oxidation,
      oxidative respiration under continuous illumination can establish an anaerobic
      environment in the culture. After 10-15 hours of anaerobiosis, sulfur-deprived
      algal cells induce a reversible hydrogenase and start to evolve H(2) gas in the
      light. Using a computer-monitored photobioreactor system, we investigated the
      behavior of sulfur-deprived algae and found that: (1) the cultures transition
      through five consecutive phases: an aerobic phase, an O(2)-consumption phase, an
      anaerobic phase, a H(2)-production phase and a termination phase; (2)
      synchronization of cell division during pre-growth with 14:10 h light:dark cycles
      leads to earlier establishment of anaerobiosis in the cultures and to earlier
      onset of the H(2)-production phase; (3) re-addition of small quantities of
      sulfate (12.5-50 microM MgSO(4), final concentration) to either synchronized or
      unsynchronized cell suspensions results in an initial increase in culture
      density, a higher initial specific rate of H(2) production, an increase in the
      length of the H(2)-production phase, and an increase in the total amount of H(2)
      produced; and (4) increases in the culture optical density in the presence of 50
      microM sulfate result in a decrease in the initial specific rates of H(2)
      production and in an earlier start of the H(2)-production phase with
      unsynchronized cells. We suggest that the effects of sulfur re-addition on H(2)
      production, up to an optimal concentration, are due to an increase in the
      residual water-oxidation activity of the algal cells. We also demonstrate that,
      in principle, cells synchronized by growth under light:dark cycles can be used in
      an outdoor H(2)-production system without loss of efficiency compared to cultures
      that up until now have been pre-grown under continuous light conditions.

PMID- 12001166
TI  - Selected amino acids protect hybridoma and CHO cells from elevated carbon dioxide
      and osmolality.
AB  - Elevated pCO(2) inhibits cell growth. This growth inhibition is accompanied by a
      decrease in intracellular pH (pHi), as well as a decrease in glycolysis. Elevated
      concentrations (mM) of some amino acids have been shown by others to protect
      cells exposed to two very different environmental stresses: nutrient starvation
      and hyperosmolality. The fact that many of the amino acids shown to have
      protective effects against other stresses are transported into the cell through a
      pHi-sensitive transporter led us to study the possibility of using these amino
      acids as protective agents under elevated pCO(2). Screening experiments using 5,
      15, and 25 mM of each amino acid showed that not all amino acids that protect
      cells from hyperosmolality protect them from elevated pCO(2). Glycine betaine and
      glycine were chosen for further characterization in both hybridoma and CHO cells.
      Asparagine and threonine were also tested in hybridoma and CHO cells,
      respectively. All amino acids tested under 195 mm Hg pCO(2)/435 mOsm/kg (50%
      growth inhibition) restored the specific growth rate (mu) in hybridoma cells to
      that observed under control conditions (40 mm Hg/320 mOsm/kg). Addition of each
      amino acid resulted in an increase in the consumption rate and intracellular
      accumulation of that amino acid. In CHO cells, glycine betaine also restored mu
      to control values, while glycine and threonine partially restored mu. In
      hybridoma cells, the higher specific antibody productivity obtained at elevated
      pCO(2) was maintained with the lowest amino acid concentration (5 mM).
      Productivity decreased toward control values with increasing amino acid
      concentrations. Elevated pCO(2) decreased the specific tPA productivity in the
      CHO cell line studied. Only glycine betaine resulted in a 20% increase in
      productivity at 195 mm Hg/435 mOsm/kg. With the exception of glycine betaine in
      hybridoma cells, amino acids did not mitigate the associated pHi decrease of at
      least 0.2 pH units at 195 mm Hg/435 mOsm/kg. pHi in hybridoma cells under
      elevated pCO(2) in the presence of glycine betaine was about 0.1 pH units below
      that of control. Amino acids had no effect on the cell size response of hybridoma
      cells, while they partially offset the increase in CHO cell size at elevated
      pCO(2). Glycine betaine, asparagine, and glycine increased the specific glucose
      consumption rate observed at 195 mm Hg/435 mOsm/kg (50% of control) to values
      greater than 70% of control in hybridoma cells. In CHO cells, only glycine
      betaine increased q(glc) (by 20%) under elevated pCO(2). All amino acids tested
      improved the cell yield from glutamine at 195 mm Hg/435 mOsm/kg in both cell
      lines.

PMID- 12001167
TI  - Metabolic pre-conditioning of cultured cells in physiological levels of insulin:
      generating resistance to the lipid-accumulating effects of plasma in hepatocytes.
AB  - Understanding the regulation of hepatocyte lipid metabolism is important for
      several biotechnological applications involving liver cells. During exposure of
      hepatocytes to plasma, as is the case in extracorporeal bioartificial liver
      assist devices, it has been reported that hepatic-specific functions, e.g.,
      albumin and urea synthesis and diazepam removal, are dramatically compromised and
      hepatocytes progressively accumulate cytoplasmic lipid droplets. We hypothesized
      that the composition of hepatocyte culture medium significantly affects lipid
      metabolism during subsequent plasma exposure. Rat hepatocytes were cultured in
      medium containing either physiological (50 microU/mL) or supra-physiological (500
      mU/mL) insulin levels for 1 week and then exposed to human plasma supplemented
      with or without amino acids. We found that insulin's anabolic effects, such as
      stimulation of triglyceride storage, were carried over from the pre-conditioning
      to the plasma exposure period. While hepatocytes cultured in high insulin medium
      accumulated large quantities of triglycerides during subsequent plasma exposure,
      culture in low insulin medium largely prevented lipid accumulation. Urea and
      albumin secretion, as well as the ammonia removal rate, were largely unaffected
      by insulin but increased with amino acid supplementation. Thus, hepatocyte
      metabolism during plasma exposure can be modulated by medium pre-conditioning and
      supplements added to plasma.

PMID- 12001168
TI  - A strategy for in vivo screening of subtilisin E reaction specificity in E. coli
      periplasm.
AB  - We developed a protocol for efficient expression of the functional serine
      protease, subtilisin E, in Escherichia coli periplasm that permits direct in vivo
      measurement of the enzyme's catalytic activity. Activity assays and SDS
      PAGE/Western blot analysis showed that the levels of expressed subtilisin varied
      and were correlated with both the culture conditions and the induction
      procedures. The highest level of subtilisin expression was achieved at 0.10-0.15%
      (w/v) of arabinose as inducer and a temperature of 20-22 degrees C, and was ca.
      eightfold higher as compared to the expression level at 30 degrees C. Cultivation
      of bacterial cells to a steady state of balanced growth before induction was
      required for uniform subtilisin expression in cell cultures growing in wells of
      microtiter plates. Amidase and esterase cell-based kinetic assays on microtiter
      plates were developed based on the direct measurement of subtilisin activity in
      vivo. Intact E. coli cells displaying wild-type, dimethylformamide-resistant, and
      temperature-resistant subtilisins were assayed on N-succinyl-Ala-Ala-Pro-Phe-p
      nitroanilide and N-acetyl-Phe-p-nitrophenyl ester for their amidase and esterase
      activity, respectively. Additionally, the periplasmic fractions were isolated
      from the three E. coli strains expressing the respective subtilisins and tested
      for amidase activity. The amidase activity of the three subtilisins was ca. 15
      fold higher than the esterolytic activity when measured in both the intact cells
      and in the periplasmic fractions. The strategy combining periplasmic expression
      of subtilisins with two cell-based kinetic assays permits rapid screening of
      subtilisin mutant libraries for desired activities.

PMID- 12001169
TI  - Chromate/nitrite interactions in Shewanella oneidensis MR-1: evidence for
      multiple hexavalent chromium [Cr(VI)] reduction mechanisms dependent on
      physiological growth conditions.
AB  - Inhibition of hexavalent chromium [Cr(VI)] reduction due to nitrate and nitrite
      was observed during tests with Shewanella oneidensis MR-1 (previously named
      Shewanella putrefaciens MR-1 and henceforth referred to as MR-1). Initial Cr(VI)
      reduction rates were measured at various nitrite concentrations, and a mixed
      inhibition kinetic model was used to determine the kinetic parameters-maximum
      Cr(VI) reduction rate and inhibition constant [V(max,Cr(VI)) and K(i,Cr(VI))].
      Values of V(max,Cr(VI)) and K(i,Cr(VI)) obtained with MR-1 cultures grown under
      denitrifying conditions were observed to be significantly different from the
      values obtained when the cultures were grown with fumarate as the terminal
      electron acceptor. It was also observed that a single V(max,Cr(VI)) and
      K(i,Cr(VI)) did not adequately describe the inhibition kinetics of either nitrate
      grown or fumarate-grown cultures. The inhibition patterns indicate that Cr(VI)
      reduction in MR-1 is likely not limited to a single pathway, but occurs via
      different mechanisms some of which are dependent on growth conditions. Inhibition
      of nitrite reduction due to the presence of Cr(VI) was also studied, and the
      kinetic parameters V(max,NO2) and K(i,NO2) were determined. It was observed that
      these coefficients also differed significantly between MR-1 grown under
      denitrifying conditions and fumarate reducing conditions. The inhibition studies
      suggest the involvement of nitrite reductase in Cr(VI) reduction. Because nitrite
      reduction is part of the anaerobic respiration process, inhibition due to Cr(VI)
      might be a result of interaction with the components of the anaerobic respiration
      pathway such as nitrite reductase. Also, differences in the degree of inhibition
      of nitrite reduction activity by chromate at different growth conditions suggest
      that the toxicity mechanism of Cr(VI) might also be dependent on the conditions
      of growth. Cr(VI) reduction has been shown to occur via different pathways, but
      to our knowledge, multiple pathways within a single organism leading to Cr(VI)
      reduction has not been reported previously.

PMID- 12001170
TI  - Modeling and kinetic analysis of the reaction system using whole cells with
      separately and co-expressed D-hydantoinase and N-carbamoylase.
AB  - We developed a kinetic model that describes a heterogeneous reaction system for
      the production of D-p-hydroxyphenylglycine from D,L-p-hydroxyphenyl-hydantoin
      using D-hydantoinase of Bacillus stearothermophilus SD1 and N-carbamoylase of
      Agrobacterium tumefaciens NRRL B11291. As a biocatalyst, whole cells with
      separately or co-expressed enzymes were used. The reaction system involves
      dissolution of substrate particles, enzymatic conversion, racemization of the L
      form substrate, and transfer of the dissolved substrate, intermediate, and
      product through the cell membrane. Because the two enzymes have different pH
      optimum, kinetic parameters were evaluated at different pH for the reaction
      systems. The model was simulated using the kinetic parameters and compared with
      experimental data, and it was found that the kinetic model well describes the
      behavior of the reaction systems using whole cells with separately and co
      expressed enzymes. Factors affecting the kinetics of the reaction systems were
      analyzed on the basis of the kinetic model. In the reaction system with
      separately expressed enzymes, racemization rate and transport of the reaction
      intermediate (N-carbamoyl-D-p-hydroxyphenylglycine) were revealed to be the
      limiting factors at neutral pH, resulting in accumulation of intermediate in the
      reaction medium. At alkaline condition, on the other hand, inhibition of N
      carbamoylase by ammonia was severe, and thereby the reaction rate significantly
      reduced. In the co-expressed enzyme system, accumulation of intermediate was
      negligible in the reaction medium, and the improved performance was observed
      compared to that with separately expressed enzymes. The present model might be
      applied for the optimization and development of the reaction system using two
      sequential enzymes.

PMID- 12001171
TI  - Full model for reversible kinetics of lipase-catalyzed sugar-ester synthesis in 2
      methyl 2-butanol.
AB  - A kinetic model derived from the ping-pong bi-bi reversible mechanism is proposed
      to described the acylation of glucose by lauric acid in 2-methyl 2-butanol
      mediated by Candida antarctica lipase at 60 degrees C. The model accounts for the
      effect of all four compounds in the reaction mixture, namely lauric acid,
      glucose, water, and lauroyl glucose ester. A supersaturated glucose solution was
      used to avoid limitations by glucose dissolution rate. Experiments with varied
      initial water content were performed to determine the effect of water on the
      initial reaction rate. The full time course of ester formation is described by
      five parameters: (a) three parameters evaluated from initial rate measurements;
      (b) the equilibrium constant, independently evaluated; and (c) one extra
      parameter fitted to the progress curve of ester formation. This reduced form of a
      full reversible kinetic model based on the ping-pong bi-bi mechanism is able to
      describe the complete course of lauroyl glucose ester synthesis. The proposed
      model provides a good fit for the experimental results.

PMID- 12001172
TI  - Microengineering neocartilage scaffolds.
AB  - Advances in micropatterning methodologies have made it possible to create
      structures with precise architecture on the surface of cell culture substrata. We
      applied these techniques to fabricate microfeatures (15-65 microm wide; 40 microm
      deep) on the surface of a flexible, biocompatible polysaccharide gel. The
      micropatterned polymer gels were subsequently applied as scaffolds for
      chondrocyte culture and proved effective in maintaining key aspects of the
      chondrogenic phenotype. These were rounded cell morphology and a positive and
      statistically significant (p < 0.0001) immunofluorescence assay for the
      production of type II collagen throughout the maximum culture time of 10 days
      after cell seeding. Further, cells housed within individual surface features were
      observed to proliferate, while serial application of chondrocytes resulted in the
      formation of cellular aggregates. These methods represent a novel approach to the
      problem of engineering reparative cartilage in vitro.

PMID- 12001173
TI  - Controlled shear affinity filtration (CSAF): a new technology for integration of
      cell separation and protein isolation from mammalian cell cultures.
AB  - Controlled shear affinity filtration (CSAF) integrates animal cell separation and
      product isolation in a single unit operation through the use of a specifically
      designed rotating disk filter with incorporated membrane chromatography column.
      Because of the decoupling of shear force and pressure generation and the specific
      hydrodynamics of the system, shear rates can be easily optimized and precisely
      controlled to maximize filtration performance while viability of the shear
      sensitive animal cells is maintained. In this study, the general methodology is
      demonstrated using the integration of Chinese hamster ovary cell separation and
      isolation of recombinant tissue plasminogen activator (t-PA) as a model example.
      Direct capture of t-PA from cell culture broth was realized by using custom-made
      affinity membranes with lysine as a robust, small molecular weight affinity
      ligand. Small-scale t-PA adsorption experiments, as well as microfiltration
      experiments, were used to design the integrated CSAF process. A Chinese hamster
      ovary batch culture was processed with a lab-scale prototype, yielding 86% of the
      t-PA in the concentrated, particle-free eluate, whereas 95% of the bulk protein
      was removed. Because the viability of the cells is not significantly affected and
      high specific flux rates can be achieved, the CSAF technology should also be well
      suited for continuous perfusion with integrated product isolation. A truly
      continuous operation could be realized with two systems in tandem configuration.

PMID- 12001174
TI  - Influence of glucose solubility and dissolution rate on the kinetics of lipase
      catalyzed synthesis of glucose laurate in 2-methyl 2-butanol.
AB  - The lipase catalyzed acylation of glucose by dodecanoic acid in 2-methyl 2
      butanol was studied. The initial reaction rate was strongly dependent on the
      dissolved glucose concentration in the medium. Several methods were shown to
      increase dissolved glucose concentrations and initial reaction rates, namely, the
      use of solid beta-glucose, amorphous solid glucose, and supersaturated glucose
      solution. Supersaturated glucose solutions in 2-methyl 2-butanol showed a high
      stability even in the presence of solid crystalline glucose. During the reaction,
      the dissolved glucose concentration falls as the reaction proceeds, before
      recovering later as more of the excess solid dissolves. However, the ester
      synthesis rate continues to fall even after glucose concentration reaches its
      minimum, so glucose dissolution rate limitation is not responsible for the
      synthesis rate decline. Experiments with added molecular sieves show that the
      main reason is the accumulation of product water. In the presence of molecular
      sieves, 70% of glucose was converted to ester, independent of the initial soluble
      glucose in the medium.

PMID- 12001175
TI  - Monitoring on-line desalted lignocellulosic hydrolysates by microdialysis
      sampling micro-high performance anion exchange chromatography with integrated
      pulsed electrochemical detection/mass spectrometry.
AB  - An on-line system based on microdialysis sampling (MD), micro-high performance
      anion exchange chromatography (micro-HPAEC), integrated pulsed electrochemical
      detection (IPED), and electrospray ionization mass spectrometry (MS) for the
      monitoring of on-line desalted enzymatic hydrolysates is presented. Continuous
      monitoring of the enzymatic degradation of dissolving pulp from Eucalyptus
      grandis as well as degradation of sugar cane bagasse in a 5-mL reaction vessel
      was achieved up to 24 h without any additional sample handling steps. Combining
      MD with micro-HPAEC-IPED/MS and on-line desalting of hydrolysates enabled
      injection (5 microL) of at least 23 samples in a study of the sequential action
      of hydrolytic enzymes in an unmodified environment where the enzymes and
      substrate were not depleted due to the perm-selectivity of the MD membrane (30
      kDa cut-off). Xylanase, phenolic acid esterase and a combination of endoglucanase
      (EG II) with cellobiohydrolase (CBH I) resulted in the production of DP 1 after
      the addition of esterase, DP 2 and DP 3 after the addition of EG II and CBH I,
      from the dissolving pulp substrate. Similar sequential enzyme addition to sugar
      cane bagasse resulted in DP 1 production after the addition of esterase and DP 1,
      DP 2 and DP 3 production after the addition of the EG II and CBH I mixture.
      Combining MS on-line with micro-HPAEC-IPED proved to be a versatile and necessary
      tool for such a study compared to conventional methods. The mass selectivity of
      MS revealed complementary information, including the co-elution of saccharides as
      well as the presence of more than one type of DP 2 in the case of dissolving pulp
      and several types of DP 2 and DP 3 for sugar cane bagasse. This study
      demonstrates the limitation of the use of retention time alone for confirmation
      of the identity of saccharides especially when dealing with complex enzymatic
      hydrolysates. In situ sampling and sample clean-up combined with on-line
      desalting of the chromatographic effluent, provides a generic approach to achieve
      real time monitoring of enzymatic hydrolysates when they are detected by a
      combination of IPED and MS.

PMID- 12001176
TI  - Monitoring of chemical and enzymatic hydrolysis of water-soluble proteins using
      flow-injection analysis with fluorescence detection and an aqueous eluant
      containing 2-p-toluidinylnaphthalene-6-sulfonate as the fluorescent probe.
AB  - The exposed hydrophobicity of proteins, which is due to the hydrophobic regions
      located on their surfaces, enhances the fluorescence intensity of the probe 2-p
      toluidinylnaphthalene-6-sulfonate (2,6-TNS) by the formation of a complex. During
      the hydrolysis of a protein, the average exposed hydrophobicity of the substrate
      continuously changes with incubation time, and these changes are immediately
      reflected by a corresponding change in the fluorescence intensity of the 2,6
      TNS/substrate complex. Therefore, 2,6-TNS seems to be a good probe to monitor the
      course of the depolymerization processes of proteins. In this work, bovine serum
      albumin and alpha-casein have been hydrolyzed both chemically and enzymatically,
      and the course of the reactions is monitored by using flow-injection analysis
      (FIA) with fluorescence detection and a buffered aqueous eluant containing 2,6
      TNS as the fluorescent probe. Results indicate that the time evolution of the
      fluorescence intensity of the 2,6-TNS/substrate complex can be correlated with
      the initial concentration of the parent protein, in mass per unit volume, the
      hydrolytic activity added, and the time evolution of the mean chain length of the
      substrate. In addition, because the time elapsed between injection of the sample
      into the FIA system and measurement of the corresponding fluorescence intensity
      is only a few seconds, this methodology could be a useful tool for on-line
      monitoring of processes for the production of protein hydrolysates.

PMID- 12001177
TI  - Platelet activation and secretion in patients with major depression, thoracic
      aortic atherosclerosis, or renal dialysis treatment.
AB  - Relatively little is known concerning the magnitude of alterations of platelet
      activation and secretion markers of patients with major depression when compared
      to patients at increased risk for, or with current, clinically significant
      atherosclerosis. Markers of in vivo platelet stimulation and secretion were
      measured under basal conditions in normal comparison subjects (n = 12) and three
      patient groups: patients diagnosed with DSM-IV major depression (n = 15),
      dialysis-dependent patients (n = 12), and patients with severe thoracic aortic
      atherosclerosis (n = 10). In comparison to normal comparison subjects, depressed
      patients and patients with thoracic aortic atherosclerosis exhibited the greatest
      platelet stimulation as detected by increased anti-LIBS platelet binding.
      Dialysis-dependent patients exhibited the highest plasma concentrations of the
      renally-excreted platelet-specific secretion protein, beta-thromboglobulin. This
      study extends previous observations of increased platelet activation in patients
      with major depression and documents similar alterations in patients with
      transesophageal echocardiography (TEE)-documented thoracic aortic
      atherosclerosis. Future studies will determine whether the magnitude of platelet
      stimulation and secretion in patients with comorbid depression and
      atherosclerotic aortic disease is greater than that observed in nondepressed
      patients with atherosclerotic aortic disease or major depression alone. These
      findings provide further evidence for either increased platelet activation and/or
      intrinsic heightened platelet reactivity as one of the biological substrates
      underlying the increased risk of depressed patients for cardiovascular disease.

PMID- 12001178
TI  - A randomized, placebo-controlled trial of paroxetine in nursing home residents
      with non-major depression.
AB  - Depression is common across a broad spectrum of severity among nursing home
      residents. Previous research has demonstrated the effectiveness of
      antidepressants in nursing home residents with major depression, but it is not
      known whether antidepressants are helpful in residents with less severe forms of
      depression. We conducted a randomized double-blind placebo-controlled 8-week
      trial comparing paroxetine and placebo in very old nursing home residents with
      non-major depression. The main outcome measure was the primary nurse's Clinical
      Impression of Change (CGI-C). Additional outcome measures were improvement on the
      interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for
      Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were
      enrolled and twenty subjects completed the trial. Placebo response was high, and
      when all subjects were considered, there were no differences in improvement
      between the paroxetine and placebo groups. Two subjects that received paroxetine
      developed delirium, and subjects that received paroxetine were more likely to
      experience a decrease in Mini Mental State Exam scores (P =.03). There were no
      differences in serum anticholinergic activity between groups. In a subgroup
      analysis of 15 subjects with higher baseline HDRS and CS scores, there was a
      trend toward greater improvement in the paroxetine group in an outcome measure
      that combined the CGI-C and interview-based measures (P =.06). Paroxetine is not
      clearly superior to placebo in this small study of very old nursing home
      residents with non-major depression, and there is a risk of adverse cognitive
      effects. Because of the high placebo response and the trend towards improvement
      in the more severely ill patients, it is possible that a larger study would have
      demonstrated a significant therapeutic effect for paroxetine as compared with
      placebo. The study also illustrates the discordance between patient and caregiver
      ratings, and the difficulties in studying very elderly patients with mood
      disorders.

PMID- 12001179
TI  - Recognition of depressive symptoms in the elderly: what can help the patient and
      the doctor.
AB  - The general public heavily underrecognizes depression and depressive symptoms.
      This underrecognition is more pronounced among elderly people, and this study is
      an initial attempt to quantify the problem in a Greek elderly sample.
      Additionally the authors attempt to identify patient-related factors, which can
      assist a subject to recognize the depressive symptoms and the general
      practitioner to note their existence. Members of senior citizen centers (n = 682)
      participated in presentations about "depression in the elderly" and completed a
      questionnaire including the GDS-4 scale, four questions concerning depression
      risk factors and a question concerning a recent visit to a physician for
      depressive symptoms. Amongst those participating, 35.8% presented depressive
      symptoms (GDS-4 > or = 2). The calculated rate for recognition of depression in
      the studied population was very low (17.3%). Patients with depressive symptoms
      were more often females and had a higher proportion of past history of depression
      and a lack of social support. Patients with a past history of depression and more
      severe forms of illness consulted a doctor more frequently. Finally, subjects
      suffering from depressive symptoms and comorbid medical illness were
      characterized by a higher proportion of past history, lack of support, and
      existence of multiple risk factors. The authors propose that the inclusion in
      public campaigns of activities with an experiential dimension, e.g., patient
      videos and the use of a very simple screening tool, such as the GDS-4 scale by
      general practitioners (GP), could be helpful in improving the recognition of
      depressive symptoms by the patient and his/her relatives and its diagnosis by the
      doctor. This proposition awaits formal proof in future studies.

PMID- 12001180
TI  - The role of early adverse experience and adulthood stress in the prediction of
      neuroendocrine stress reactivity in women: a multiple regression analysis.
AB  - Sensitization of stress-responsive neurobiological systems as a possible
      consequence of early adverse experience has been implicated in the
      pathophysiology of mood and anxiety disorders. In addition to early adversities,
      adulthood stressors are also known to precipitate the manifestation of these
      disorders. The present study sought to evaluate the relative role of early
      adverse experience vs. stress experiences in adulthood in the prediction of
      neuroendocrine stress reactivity in women. A total of 49 women (normal
      volunteers, depressed patients, and women with a history of early abuse)
      underwent a battery of interviews and completed dimensional rating scales on
      stress experiences and psychopathology, and were subsequently exposed to a
      standardized psychosocial laboratory stressor. Outcome measures were plasma
      adrenocorticotropin (ACTH) and cortisol responses to the stress test. Multiple
      linear regression analyses were performed to identify the impact of demographic
      variables, childhood abuse, adulthood trauma, major life events in the past year,
      and daily hassles in the past month, as well as psychopathology on hormonal
      stress responsiveness. Peak ACTH responses to psychosocial stress were predicted
      by a history of childhood abuse, the number of separate abuse events, the number
      of adulthood traumas, and the severity of depression. Similar predictors were
      identified for peak cortisol responses. Although abused women reported more
      severe negative life events in adulthood than controls, life events did not
      affect neuroendocrine reactivity. The regression model explained 35% of the
      variance of ACTH responses. The interaction of childhood abuse and adulthood
      trauma was the most powerful predictor of ACTH responsiveness. Our findings
      suggest that a history of childhood abuse per se is related to increased
      neuroendocrine stress reactivity, which is further enhanced when additional
      trauma is experienced in adulthood.

PMID- 12001181
TI  - Circuits and systems in stress. I. Preclinical studies.
AB  - This paper reviews the preclinical literature related to the effects of stress on
      neurobiological and neuroendocrine systems. Preclinical studies of stress provide
      a comprehensive model for understanding neurobiological alterations in post
      traumatic stress disorder (PTSD). The pathophysiology of stress reflects long
      standing changes in biological stress response systems and in systems involved in
      stress responsivity, learning, and memory. The neural circuitry involved includes
      systems mediating hypothalamic-pituitary-adrenal (HPA) axis, norepinephrine
      (locus coeruleus), and benzodiazepine, serotonergic, dopaminergic, neuropeptide,
      and central amino acid systems. These systems interact with brain structures
      involved in memory, including hippocampus, amygdala, and prefrontal cortex.
      Stress responses are of vital importance in living organisms; however excessive
      and/or repeated stress can lead to long-lasting alterations in these circuits and
      systems involved in stress responsiveness. Intensity and duration of the
      stressor, and timing of the stressor in life, have strong impact in this respect.

PMID- 12001182
TI  - Chronic inositol treatment reduces depression-like immobility of Flinders
      Sensitive Line rats in the forced swim test.
AB  - Inositol, a precursor of the PIP cycle that was reported to have therapeutic
      effects in depressive patients and to be effective in two animal models of
      depression, was evaluated in the forced swim test using the genetic Flinders
      Sensitive Line (FSL) rats model of depression. Groups of rats were tested in a 2
      x 2 design with Strain (FSL or Control) as one factor and Drug (Inositol or
      Placebo) as the second factor. Rats received chronic treatment (daily for 14
      days) with inositol (1.2 g/kg) or placebo (1:2 glucose/mannitol solution). On day
      14 rats were exposed to the forced swim test for 5 min and their behavior
      videotaped. Tapes were analyzed for three levels of activity: immobility,
      swimming, and vigorous struggle. Inositol countered the exaggerated immobility of
      FSL rats in the forced swim test, without affecting control animals. Data support
      our previous suggestion of inositol as a potential antidepressant.

PMID- 12001183
TI  - Pregnancy outcome in fetuses with increased nuchal translucency and normal
      karyotype.
AB  - OBJECTIVE: This study was conducted to evaluate pregnancy outcome and mid- and
      long-term prognosis of cases with nuchal translucency > or =4 mm and normal
      karyotype. METHODS: Retrospective analysis of 160 cases who presented with a
      nuchal translucency > or =4 mm when the CRL was between 45 and 84 mm was
      undertaken. Cystic hygromas were excluded. When the karyotype was normal a
      detailed anomaly scan was performed at 20 to 24 weeks followed by serial
      ultrasound examination. Clinical examination of the neonates was performed by a
      paediatrician. Long-term follow-up was completed through a questionnaire filled
      in by parents, GPs and paediatricians. RESULTS: 160 fetuses had an NT > or =4 mm.
      44.3% had an abnormal karyotype. Of the 55.7% with normal karyotypes, 74 % did
      not show any abnormalities on follow-up ultrasound scan. Mid- and long-term
      outcome was known in 91% of the cases. 6.4% had a malformation diagnosed only at
      birth. Among the normal neonates, 11.1% are considered to have a significant
      neurological handicap or orthopaedic problems at 12 to 72 months of age.
      CONCLUSION: In an unselected population, NT > or =4 mm is associated with a high
      incidence of chromosomal and non chromosomal abnormalities. Even when the fetal
      karyotype and serial ultrasound examinations are considered to be normal, the
      risk of fetal malformation and developmental delay should not be underestimated.

PMID- 12001184
TI  - Detection and false-positive rates of maternal serum markers for Down syndrome
      screening according to maternal age in women over 35 years of age. A study of the
      agreement of eight dedicated software packages.
AB  - Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women >
      or =35 years in an attempt to reduce the need for invasive procedures and thereby
      avoid their side effects. Our objective was to compare, in women > or =35, eight
      different software packages dedicated to second trimester MSS, thus providing
      reliable data for patient counselling. A simulation study was carried out on 189
      sera from women with Down syndrome fetuses and 11 962 sera from mothers of
      unaffected babies. The first step was to estimate the joint distribution of alpha
      fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG). The
      second step was to calculate trisomy 21 detection and false-positive rates for
      each software according to maternal age (35-45 years), using the usual 1:250 risk
      threshold. Agreement between software packages was measured using 2 x 2 kappa
      coefficients. Detection rates and false-positive rates increased with maternal
      age. Depending on the software, 57-71% detection rates were achieved at 35 years
      with 12-18% false-positive rates. At 45 years, 61-100% detection rates were
      achieved with 66-95% false-positive rates. Up to 39 years, all softwares were
      concordant (kappa coefficients >0.75). In the range 35-45 years, false-positive
      and detection rates increased substantially with maternal age and differences
      between software packages are observed.

PMID- 12001185
TI  - Funipuncture for fetocide in late termination of pregnancy.
AB  - The most widely used method for fetocide in late termination of pregnancy for
      fetal abnormalities (TOPFA) consists of injecting of potassium chloride (KCl)
      into the fetal heart and is likely to be painful after 22 weeks of gestation. We
      studied ten consecutive women undergoing TOPFA between 22 and 38 weeks. This
      technique for fetocide consisted of a single umbilical vein puncture under
      ultrasound guidance with injections of sufentanil 5 microg followed by KCl 2 g.
      No electrocardiographic modifications could be observed and maternal plasma
      potassium levels did not show any significant variation throughout the procedure.
      Fetal umbilical phlebotomy for fetal analgesia followed by fetocide therefore
      appears to be a safe procedure for the mother and allows the fetus to die without
      pain when late termination of pregnancy (TOP) is indicated.

PMID- 12001186
TI  - Prenatal diagnosis in glycogen storage diseases.

PMID- 12001187
TI  - Prenatal diagnosis of common aneuploidies using quantitative fluorescent PCR.
AB  - OBJECTIVE: Quantitative fluorescence-polymerase chain reaction (QF-PCR) has
      recently been used for the detection of common chromosomal aneuploidies in
      prenatal diagnosis. Here we describe our experience in prenatal diagnosis of 1100
      samples. METHODS: Extraction of DNA was performed from amniotic fluid, chorionic
      villus samples (CVS), fetal blood and fetal tissue samples, using a simple, rapid
      protocol. Fluorescent multiplex PCR products of single tandem repeats (STRs)
      located on chromosomes 13, 18, 21, X and Y were then analyzed on an automated
      laser fluorescent sequencer. All samples were analyzed with at least two
      polymorphic markers for chromosomes 13, 18 and 21 and one for the X chromosome.
      The amelogenin locus was used for sexing. Analysis was performed twice on
      affected samples. When miscellaneous results were obtained extra markers were
      used. RESULTS: We evaluated the usefulness of different markers in the Greek
      population. In a total of 1100 samples, 25 chromosome aberrations were
      identified, including trisomy 13, 18 and 21, XYY, triploidies 69,XXX and 69,XXY
      and one Turner mosaic. All results but three were consistent with conventional
      cytogenetic analysis. One mosaic was missed. Most bloodstained samples were
      successfully analyzed. CONCLUSION: Successful analysis of a large number of
      prenatal samples proves QF-PCR to be an efficient adjunct in routine prenatal
      diagnosis.

PMID- 12001188
TI  - Prenatal diagnosis of brain abnormalities in Wolf-Hirschhorn (4p-) syndrome.
AB  - OBJECTIVES: Although there have been occasional reports of prenatal diagnosis of
      this syndrome, most cases are diagnosed postnatally. The objective was to
      evaluate the presence of brain abnormalities in the prenatal diagnosis of Wolf
      Hirschhorn syndrome. METHODS: Prenatal ultrasound and MRI examination of the
      fetal brain were performed in a case of Wolf-Hirschhorn syndrome. A comprehensive
      review of Wolf-Hirschhorn syndrome reported between 1960 and 2000 in the
      literature was carried out. RESULTS: The late diagnosis of a growth-retarded
      fetus with normal amniotic fluid volume, normal Doppler and negative infection
      screen calls for a detailed examination of the fetal brain and heart. Multifocal
      white matter lesions and periventricular cystic changes, which are often
      attributed to perinatal distress, are possible prenatal features causing
      suspicion of 4p- syndrome in an IUGR fetus. CONCLUSION: Subtle abnormalities on
      ultrasound may suggest a chromosomal problem. Standard cytogenetics cannot always
      demonstrate a microdeletion. High-resolution banding and molecular analysis can
      help to confirm the diagnosis.

PMID- 12001189
TI  - Interrupted aortic arch type A with 22q11 deletion: prenatal detection of an
      unusual association.
AB  - Interrupted aortic arch is a rare, severe congenital heart defect subdivided into
      three types, A, B and C, according to the site of interruption. Type C is by far
      the least common form of interrupted aortic arch (less than 5% of cases), type A
      is commonly an isolated defect whereas type B is frequently associated with 22q11
      deletion. Differentiation of interrupted aortic arch type A from type B by
      prenatal echocardiography is possible but difficult; it needs to be done on the
      basis of observation of reliable morphological indicators which point to the
      correct diagnosis. Here we report the first case of prenatal diagnosis of
      interrupted aortic arch type A associated with 22q11 deletion. The significance
      of this association is not yet clear, since 22q11 genes mainly affect embryonic
      cardiovascular morphogenesis of those regions whose development is critically
      dependent on neural crest cell migration and function, affected in type B defect
      but not in type A.

PMID- 12001190
TI  - Prenatal ultrasound diagnosis of frontonasal dysplasia.
AB  - We report a case of prenatal ultrasound diagnosis of frontonasal dysplasia. This
      represents a very rare disorder involving the face (hypertelorism, median cleft
      lip, absence of the nasal tip) and often the central nervous system (CNS)
      (cranium bifidum occultum, ethmoidal cephalocele, agenesis of the corpus
      callosum). Although several of the typical anomalies are diagnosable by
      ultrasound in utero (hypertelorism, median cleft lip, anterior cephalocele), very
      few cases have been reported prenatally, the present being only the third. In the
      present case, hemimegalencephaly is first reported among the anomalies possibly
      associated with frontonasal dysplasia. The diagnosis was made at 22 weeks'
      gestation and was confirmed by necropsy following termination of pregnancy.

PMID- 12001191
TI  - Prenatal diagnosis of a rhodopsin mutation using chemical cleavage of the
      mismatch.
AB  - OBJECTIVE: Mutations of the rhodopsin gene are responsible for autosomal dominant
      or recessive retinitis pigmentosa (RP). The present study reports the first
      prenatal diagnosis performed on chorionic villi biopsy of a pregnant woman
      affected by a severe form of autosomal dominant transmitted RP, due to the
      Arg135Trp substitution. METHODS: The rhodopsin gene was analysed by automated
      direct sequencing and, for the first time, by fluorescence-assisted mismatch
      analysis (FAMA). The latter is an inexpensive, rapid and particularly sensitive
      method, based on the chemical cleavage of the mismatch in heteroduplex DNA
      molecules marked with strand-specific fluorophores. RESULTS: FAMA is a feasible
      procedure for prenatal molecular diagnosis of rhodopsin mutations. The redundancy
      of signals obtained by FAMA and its sensitivity make it suitable for identifying
      exactly the position of the mutation and the nucleotide substitution.
      CONCLUSIONS: An association is proposed between FAMA and automated direct
      sequencing procedures, in order to achieve optimal results in terms of
      reliability for prenatal diagnosis of rhodopsin mutations.

PMID- 12001192
TI  - The variation of risk estimates through pregnancy in second trimester maternal
      serum screening for Down syndrome.
AB  - The variation of risk estimates in second trimester maternal serum screening for
      Down's syndrome has been shown to be considerable in quality control schemes,
      i.e. UKNEQAS. We studied the biological variation of risk estimates in 16 women
      through pregnancy. The maternal serum markers alpha-fetoprotein (AFP), human
      chorionic gonadotrophin (hCG), unconjugated estriol (uE3) and beta-hCG were
      determined six times during late first to late second trimester, and the
      associated likelihood ratios for Down syndrome were calculated. The interpersonal
      variation of markers, as well as that of the likelihood ratio, was much greater
      than the intrapersonal variation. The average intrapersonal standard deviation
      (SD) of the triple test log likelihood ratio was 0.2291, corresponding to a
      central 95-percentile interval 0.36-2.81 of the likelihood ratio. The
      interpersonal SD of the log likelihood ratio was 0.5482, corresponding to a
      central 95-percentile interval 0.08-11.87 of the likelihood ratio. The large
      difference between the intra- and interpersonal variation makes it unlikely that
      biological variation through pregnancy is a major contributor to the variation of
      risk estimates obtained several times in the same pregnancy. Rather, improvements
      in analytical quality and laboratory management must be expected to result in
      reduced variation and, in consequence, better performance of screening.

PMID- 12001193
TI  - Prenatal diagnosis of apparently isolated unilateral multicystic kidney:
      implications for counselling and management.
AB  - Cases where initial prenatal diagnosis was made of isolated unilateral
      multicystic kidney (UMCK) were reviewed to determine appropriate counselling and
      management strategies. For the 73 cases, chromosome abnormalities, pregnancy
      complications and family histories were reviewed. In addition, subsequently
      diagnosed birth defects, and pediatric medical and surgical outcomes were
      available for 54 cases. Of those with outcome information available renal/genital
      urinary tract abnormalities were diagnosed subsequently in 33% and non-renal
      abnormalities in 16% of cases. Of the non-renal abnormalities, congenital heart
      defects were most frequent (7%). One chromosome abnormality, a trisomy 21, was
      present among 32 cases where karyotypes were known (3%). Amniotic fluid volume
      abnormalities were present in 11 cases but not predictive of associated
      anomalies, with the exception of one case where polyhydramnios accompanied
      multiple malformations consistent with VATER association. A family history of
      structural renal anomalies was reported in 11 cases (20%). There were 14 cases of
      partial or complete involution (25%), including two cases of complete prenatal
      involution of the cystic kidneys. No long-term associated morbidity such as
      hypertension or malignancy was present in our cohort. Based on our study and
      corroborating literature, amniocentesis should be offered to women when a
      seemingly isolated UMCK is detected on routine prenatal ultrasound. Furthermore,
      a detailed ultrasound with careful assessment of the fetal heart and
      contralateral kidney is indicated at diagnosis and during the third trimester to
      assess for further evidence of structural abnormalities, as well as amniotic
      fluid volume abnormalities. Careful assessment of the newborn is indicated with
      appropriate speciality referral as required.

PMID- 12001194
TI  - A case report of prenatally diagnosed ophthalmo-acromelic syndrome type
      Waardenburg.
AB  - Ophthalmo-acromelic syndrome type Waardenburg is an extremely rare autosomal
      recessive syndrome comprising eye malformations ranging from true anophthalmia to
      mild microphthalmia with acromelic malformations. We report a case of ophthalmo
      acromelic syndrome type Waardenburg diagnosed prenatally.

PMID- 12001195
TI  - Stereological quantification of placental villus vascularization and its relation
      to umbilical artery Doppler flow in intrauterine growth restriction.
AB  - The aim of this study was to investigate the changes in the number of vessels
      within tertiary stem villi and intermediate/terminal villi which may be
      responsible for the abnormalities in placental vascular resistance and Doppler
      velocity index values in growth-restricted fetuses. The placentas of 20 cases
      with intrauterine growth restriction and 30 cases which were appropriate for
      gestational age were studied. The umbilical artery resistance index, pulsatility
      index and systolic to diastolic ratio were measured in each case. The vessels
      were quantified by a stereological method described previously and vascular
      surface density and the volume portion of the villi were calculated. The
      placentas of preterm and term cases with intrauterine growth restriction
      displayed significant reductions in the vascular surface density of stem and
      intermediate/terminal villi and volume portion of intermediate/terminal villi
      stroma when compared with gestation-matched normally grown cases (p<0.05). There
      was no significant correlation between Doppler index values of the umbilical
      artery and the stereological parameters of the intermediate/terminal and stem
      villi in the intrauterine growth restriction group (p>0.05). Some of the
      pregnancies with intrauterine growth restriction (six patients) with normal
      Doppler flow velocity waveforms had reduced vascularization in the placentas, and
      these pregnancies were found to have no perinatal complications. We conclude
      that,although the placental villi show reduced vascularization in pregnancies
      with intrauterine growth restriction, the Doppler indices may be normal and this
      normal flow pattern is related to reduced complication rate.

PMID- 12001196
TI  - Prenatal diagnosis of partial agenesis of the corpus callosum in a fetus with
      thanatophoric dysplasia type 2.
AB  - A fetus with thanatophoric dysplasia type 2 (TD2) associated with cloverleaf
      skull and abnormal development of the corpus callosum is reported. This case
      represents the first prenatal direct visualization of a partial agenesis of the
      corpus callosum (ACC) using high-resolution ultrasonography and colour power
      Doppler, which was confirmed by post-mortem magnetic resonance imaging (MRI). The
      causal link between cloverleaf skull in TD and partial ACC is discussed.

PMID- 12001197
TI  - Fetal magnetocardiography: development of the fetal cardiac time intervals.
AB  - OBJECTIVES: To analyse the physiologic development of fetal cardiac time
      intervals throughout gestation using fetal magnetocardiography (FMCG). METHODS:
      FMCG data of 163 uncomplicated pregnancies (19th and 42nd gestational week) were
      analysed. Mean value, standard deviation, minimum and maximum of the duration of
      the P-wave, the QRS-complex, the PR and the QT-interval were plotted against
      gestational age. RESULTS: QRS-complex, P wave and QT-interval showed a
      significant lengthening between the 20th and 42nd gestational week. The mean of
      the QRS complex raised from 36+/-4.7 ms (week 21-24) up to 48+/-5.2 ms (> or
      =37th week), (p=0.0001). The mean of the P-wave was between 47+/-5.9 ms (week 21
      24) and 53+/-9.5 ms (> or =37th week), (p=0.05) and the mean of the QT-interval
      was 198+/-18 ms (week 21-24) and increased up to 244+/-23.9 ms (> or =37th week),
      (p=0.009). The PR-interval did not show a correlation with gestational age.
      CONCLUSION: FMCG provides sufficient information about all parts of the fetal
      cardiac conduction system from the 19th gestational week on. It offers the
      possibility to analyse the shape and the duration of the PQRST-complex.

PMID- 12001198
TI  - Prenatal findings in a monozygotic twin pregnancy with Costello syndrome.
AB  - This report describes the prenatal findings in monozygotic twins with Costello
      syndrome. At 16 weeks one twin had 9 mm of nuchal oedema: coarctation of the
      aorta was diagnosed after birth. At 22(5/7) weeks relative macrocephaly, mild
      pyelectasia and moderate polyhydramnios were noted in both twins. In the
      following 4 weeks the polyhydramnios increased significantly without
      visualisation of filling of the stomach. Between 27(5/7) and 30(2/7) weeks a
      total of 9 l amniotic fluid was drained and at 30(4/7) weeks prelabor premature
      rupture of membranes (PPROM) occurred followed by premature labor and delivery.
      The neonatal period was complicated by growth retardation, deglutition problems,
      hypotonia, cardiac and respiratory problems. Both twins died on Day 57 because of
      respiratory insufficiency.

PMID- 12001199
TI  - Maternal uniparental isodisomy 10 and mosaicism for an additional marker
      chromosome derived from the paternal chromosome 10 in a fetus.
AB  - We report a case of maternal isodisomy 10 combined with mosaic partial trisomy 10
      (p12.31-q11.1). Chromosome examinations from a CVS sample showed a karyotype
      47,XX,+mar/46,XX [corrected]. The additional marker chromosome which was present
      in 6/25 interphase nuclei was shown by fluorescence in situ hybridization (FISH)
      to have been derived from a pericentromeric segment of chromosome 10. DNA
      analysis was performed from umbilical cord blood from the fetus after termination
      of the pregnancy at 18 weeks. The results showed that the two structurally normal
      chromosomes 10 were both of maternal origin, whereas the marker chromosome
      derived from the father. Autopsy of the fetus revealed hypoplasia of heart,
      liver, kidneys and suprarenal glands, but, apart from a right bifid ureter, no
      structural organ abnormalities. This fetus represents the second reported
      instance of a maternal uniparental disomy (UPD) 10.

PMID- 12001200
TI  - First-trimester sonographic diagnosis of distal urethral atresia with
      megalourethra in VACTERL association.
AB  - Congenital megalourethra is a rare disorder. We present an early case diagnosed
      in the first trimester. Prenatal ultrasound showed a megalourethra with a normal
      fetal bladder, hyperechogenic cystic right kidney and single umbilical artery.
      After termination of pregnancy, necropsy confirmed all sonographic findings and
      revealed other malformations (spina bifida occulta, anal atresia, tracheo
      oesophageal fistula, brachydactylia) resulting in the diagnosis of VACTERL
      association. The prenatal diagnostician should seek histological examination
      firstly to confirm his findings and secondly to avoid missing associations and
      inherited malformations.

PMID- 12001201
TI  - A simple and effective approach for detecting maternal cell contamination in
      molecular prenatal diagnosis.
AB  - The presence of maternal cells in fetal samples constitutes a serious potential
      source for prenatal misdiagnosis. Here we present our approach for detecting
      maternal cell contamination (MCC) at prenatal diagnosis for eight monogenic
      disorders (autosomal recessive: beta-thalassaemia, sickle-cell anaemia, cystic
      fibrosis, prelingual deafness; autosomal dominant: achondroplasia, Huntington
      disease, myotonic dystrophy, neurofibromatosis type I; X-linked: spinobulbar
      muscular atrophy). Our aim was to apply a simple and low-cost approach, which
      would easily and accurately provide information on the fetal tissue MCC status.
      MCC testing was applied to cases of recessive inheritance where the primary
      mutation screening of the fetus revealed the presence of the maternal mutation,
      to cases concerning dominant inheritance and to cases of multiple gestation. The
      potential presence of maternal cells was determined by the amplification of the
      3'-HVR/APO B, D1S80, THO1 and VNTRI of vWf polymorphic loci, which have
      previously demonstrated high heterozygosity in Caucasians. Among 135 prenatal
      diagnoses, 44 finally needed to be tested for MCC (32.6%). MCC was detected in
      four cases, where DNA was isolated directly from chorionic villi samples (CVS),
      and in one case with DNA isolated directly from amniotic fluid (AF). In almost
      90% of cases a simple test of one polymorphic locus provided sufficient
      information about MCC. The choice of the appropriate locus is therefore
      essential, while the simultaneous screening of both parents provides the means
      for distinguishing non-informative sites about MCC.

PMID- 12001202
TI  - Perinatal hepatic infarction in twin-twin transfusion.
AB  - We report a case of a twin pregnancy which was complicated by a twin-twin
      transfusion in which the recipient twin was noted to have an intra-abdominal
      echogenic mass. This twin died at two days of age of hepatic infarction. The
      donor twin was healthy at birth, at thirty weeks' gestation, and did not have any
      subsequent problems. Fetal intra-abdominal echogenicity may be a marker of
      hepatic infarction.

PMID- 12001203
TI  - Isolated sulfite oxidase deficiency: mutation analysis and DNA-based prenatal
      diagnosis.
AB  - Isolated sulfite oxidase deficiency is an autosomal recessive, neurological
      disorder resulting from a defect in SUOX, the gene encoding the enzyme that
      catalyzes the terminal reaction in the sulfur amino acid degradation pathway. In
      its classical, severe form, sulfite oxidase deficiency leads to intractable
      seizures, severe and progressive brain pathology and death at an early age. We
      report here on clinical features and mutational analysis of the genetic defect in
      a newborn with sulfite oxidase deficiency. Cultured fibroblasts from this patient
      exhibited no detectable sulfite oxidase activity, and a unique four base pair
      deletion was present in the cDNA isolated from the same source. Identification of
      the same genetic defect in a heterozygous state in each of the parents and the
      monitoring of subsequent pregnancies in this family by DNA-based prenatal
      diagnosis are also described. The deletion mutation was identified in a
      homozygous state in uncultured chorionic villus tissue from the second pregnancy
      that was subsequently terminated. In the third pregnancy, the presence of sulfite
      oxidase activity and identification of the mutation in a heterozygous state
      suggested that the fetus was not affected. This pregnancy resulted in the birth
      of a normal child.

PMID- 12001204
TI  - Factors affecting outcomes of prenatally-diagnosed tumours.
AB  - OBJECTIVE: The outcomes of prenatally-diagnosed tumours affect obstetrical
      management and parental decisions. The present study reviews the factors
      affecting outcomes for fetuses with prenatally-diagnosed tumours. METHODS:
      Medical records of all fetuses referred to our institutions with antenatally
      diagnosed tumours were reviewed for the type and location of the tumours, results
      of treatment and/or causes of death. RESULTS: From January 1994 to May 2001,
      there were 15 fetuses with antenatally- diagnosed tumours: mesoblastic nephroma
      (MN) (n=2); neuroblastoma (NB) (n=2); cystic hygroma (CH) (n=3); intracranial
      germ cell tumour (IGCT) (n=2); sacrococcygeal teratoma (SCT) (n=3) and
      haemangioma (liver, n=2; limb, n=1). One mother had termination of pregnancy for
      her fetal SCT. Three mothers had Caesarean section for large fetal heads (CH,
      n=2; IGCT, n=1). Three fetuses died; two with IGCT and one with SCT, who died of
      heart failure. Two newborns with CH needed emergency intubation and, later, one
      of them had tracheostomy. One baby had cardiac failure resulting from a lower
      limb haemangioma and needed drug therapy. All solid tumours (MN, NB, SCT) of the
      live births had no recurrence after surgery with or without adjuvant
      chemotherapy. CONCLUSION: Prenatally-diagnosed tumours without any other
      associated abnormality cause morbidity and mortality because of their location
      and vascularity. Solid tumours are relatively benign.

PMID- 12001205
TI  - Current awareness in prenatal diagnosis.

PMID- 12001207
TI  - Orientation control and fixation of discotic liquid crystal.
AB  - We established hybrid, horizontal, vertical, and vertical-twisted alignment of
      discotic liquid crystals on web-coating thin film. Newly developed materials are
      the photopolymerizable discotic liquid crystals, in order to fix desired novel
      alignment, the alignment promoters that deposit toward air surface during web
      coating, followed by drying of solvent, and then accomplish desired alignment of
      liquid crystals, the alignment layers that promote desired alignment of liquid
      crystals from the substrate side and the chiral agents, which have strong chiral
      powers in small amounts. Hybrid aligned discotic liquid crystal thin film has
      proven quite effective in expanding the viewing angle of thin film transistor
      liquid crystal displays.

PMID- 12001208
TI  - Mesoscopic structure and properties of liquid crystalline mesophase pitch and its
      transformation into carbon fiber.
AB  - The history and present state of the art in the chemistry of mesophase pitch,
      which is an important precursor for carbon fiber and other high-performance
      industrial carbons, are reviewed relative to their structural properties. The
      structural concepts in both microscopic and macroscopic views are summarized in
      terms of the sp(2) carbon hexagonal plane as a basic unit common to graphitic
      materials, its planar stacking in clusters, and cluster assembly into
      microdomains and domains, the latter of which reflect the isochromatic unit of
      optical anisotropy. Such a series of structural units is described in a
      semiquantitative manner corresponding to the same units of graphitic materials,
      although the size and stacking height of the hexagonal planes (graphitic sheets)
      are very different. Mesophase pitch is a liquid crystal material whose basic
      structural concepts are maintained in the temperature range of 250 to 350 degrees
      C. The melt flow and thermal properties are related to its micro- and mesoscopic
      structure. The structure of mesophase-pitch-based carbon fiber of high tensile
      strength, modulus, and thermal conductivity has been formed through spinning, and
      has inherited the same structural concepts of mesophase pitch. Stabilization
      settles the structure in successive heat treatments up to 3000 degrees C.
      Carbonization and graphitization enable growth of the hexagonal planes and their
      stacking into units of graphite. Such growth is governed and controlled by the
      alignment of micro- and mesoscopic structures in the mesophase pitch, which
      define the derived carbon materials as nanostructural materials. Their properties
      are controlled by the nanoscopic units that are expected to behave as
      nanomaterials when appropriately isolated or handled.

PMID- 12001209
TI  - Mechanistic study of partial oxidation of methane to syngas using in situ time
      resolved FTIR and microprobe Raman spectroscopies.
AB  - In situ time-resolved Fourier transform infrared (FTIR) and microprobe Raman
      spectroscopies were used to characterize the reaction mechanisms of the partial
      oxidation of methane to syngas over SiO(2)- and gamma-Al(2)O(3)-supported rhodium
      and ruthenium catalysts. The interaction of both pure methane and a
      methane/oxygen mixture at a stoichiometric feed ratio with an oxygen-rich
      catalyst surface led to the formation of CO2 and H(2)O as the primary products.
      For the H(2)-pretreated samples, the reaction mechanisms with the catalysts
      differ. Only Rh/SiO(2) is capable of catalyzing the direct oxidation of methane
      to syngas, while syngas formation over Rh/gamma-Al(2)O(3), Ru/SiO(2), and
      Ru/gamma-Al(2)O(3) can be achieved mainly via a combustion-reforming scheme. The
      significant difference in the mechanisms for partial oxidation of methane to
      syngas over the catalysts can be correlated to the differences in the
      concentration of oxygen species (O(2-)) on the catalyst surface during the
      reaction, mainly due to the difference in the nature of the metals and supports.

PMID- 12001210
TI  - Biarylic biscarbazole alkaloids: occurrence, stereochemistry, synthesis, and
      bioactivity.
AB  - The structurally and pharmacologically intriguing but stereochemically initially
      disregarded small class of biarylic biscarbazole alkaloids is presented, starting
      with an introduction of the different structural patterns found in nature. For
      the construction of the biaryl bond, mainly biomimetic oxidative coupling
      reactions were used, as shown for the natural products bismurrayaquinone-A, bis-2
      hydroxy-3-methylcarbazole, clausenamine-A, and murrastifoline-F. For most of
      these compounds, a resolution of the respective atropo-enantiomers succeeded
      either directly, by high-performance liquid chromatography by HPLC on a chiral
      phase, or via atropo-diastereomers, after derivatization with a chiral auxiliary.
      The absolute configurations of the pure enantiomers were assigned by comparison
      of experimental (CD) spectra with those quantum chemi-cally calculated, or, for
      atropo-diastereomeric derivatives, by means of ROESY investigations and X-ray
      crystallography. Ullmann-type coupling conditions were also found to be feasible
      for the construction of the 2,2'-biscarbazole core, necessitating a completely
      regioselective 2-bromination protocol. The first atroposelective synthesis of
      such a basic target structure was achieved by application of the "lactone
      methodology," giving rise to an atropisomeric ratio of 85 : 15. Some of the
      biscarbazole alkaloids and their derivatives were found to have interesting
      bioactivities, and for the first time, the natural atropo-enantiomeric ratio in
      the plants was determined for one of these compounds, murrastifoline-F.

PMID- 12001212
TI  - Meeting the challenge: the future of the anatomical sciences in medical school
      curricula.

PMID- 12001213
TI  - From college to clinic: reasoning over memorization is key for understanding
      anatomy.
AB  - Anatomy and physiology are taught in community colleges, liberal arts colleges,
      universities, and medical schools. The goals of the students vary, but educators
      in these diverse settings agree that success hinges on learning concepts rather
      than memorizing facts. In this article, educators from across the postsecondary
      educational spectrum expand on several points: (1) There is a problem with
      student perception that anatomy is endless memorization, whereas the ability to
      manage information and use reasoning to solve problems are ways that
      professionals work. This misperception causes students to approach the subject
      with the wrong attitude. (2) The process of learning to use information is as
      important as the concepts themselves. Using understanding to explain and make
      connections is a more useful long-term lesson than is memorization. Anatomy
      should be presented and learned as a dynamic basis for problem solving and for
      application in the practice and delivery of quality health care. (3) Integration
      of form and function must be explicit and universal across all systems. (4) Using
      only models, images, audiovisuals, or computers cannot lead students to the
      requisite reasoning that comes from investigative dissection of real tissue. (5)
      Some undergraduate courses require students to memorize excessive musculoskeletal
      detail. (6) Learning tissue biology is a particular struggle for medical students
      who have no background from an undergraduate course. (7) Medical professors and
      students see benefits when students have taken undergraduate courses in anatomy,
      histology, and physiology. If medical schools suggest these electives to
      applicants, medical students might arrive better prepared and, thus, be able to
      learn clinical correlations more efficiently in the limited allocated time of
      medical school curricula.

PMID- 12001214
TI  - The new face of gross anatomy.
AB  - The nature of anatomy education has changed substantially over the past decade
      due to both a new generation of students who learn differently from those of past
      years and the enormity of advances in anatomical imaging and viewing. At Mount
      Sinai School of Medicine, our anatomy courses have been designed to meld classic
      dissection with the tools physicians and surgeons will use tomorrow. We introduce
      students to the newest technologies available for viewing the body, such as
      minimally invasive approaches, ultrasonography, three-dimensional visualizations,
      multi-axial computerized image reconstructions, multi-planar magnetic resonance
      imaging, and plastinated prosections. Students are given a hands-on, team
      building experience operating laparoscopes in the laboratory. A great strength of
      our program is the important and active participation by faculty from 15
      different basic and clinical departments, including several chairs and voluntary
      faculty. This interdisciplinary approach brings to our students direct, one-on
      one encounters or presentations by our finest physicians and surgeons and our
      core anatomy faculty. In addition, the presence of many teaching assistants drawn
      from upper classmen and advanced graduate students adds an additional, vibrant
      dimension. Our anatomy programs for medical/graduate students and postgraduates
      are structured around three simple principles: (1) it is a privilege to teach,
      (2) we enlist only passionate teachers, and (3) it is our role to instill
      appreciation and respect for human form.

PMID- 12001215
TI  - Embryology in the medical curriculum.
AB  - Embryology as a field is in a period of unprecedented change in its knowledge
      base. Similarly, this is a period of great change in medical curricular planning.
      One of the most significant questions in embryology education for medical
      students is how much of the "new" molecular embryology to mix with the "old"
      developmental anatomy approach. The other question is the most effective venue
      for instruction in medical embryology. Not all medical curricula have the same
      objectives; nor do they use the same educational approach. With that in mind,
      this review outlines several ways in which medical embryology can be offered and
      how it can be integrated into the medical curriculum. It also lays out topics
      that are worthy of inclusion in a modern embryology course or sequence.

PMID- 12001216
TI  - Medical neurobiology: do we teach neurobiology in a format that is relevant to
      the clinical setting?
AB  - During a period of unprecedented growth in technology that allows imaging of the
      body in elegant detail, anatomy as a discipline has, in some instances, become
      marginalized. This may be seen in a reduction of time allotted to anatomy,
      reduction or elimination of laboratory experiences, or shifting of anatomy
      teaching to clinical departments. One potential cause of this marginalization is
      the fact that anatomy is frequently taught in a format that is not useful in, or
      even applicable to, the clinical setting. At the University of Mississippi
      Medical Center, the Medical Neurobiology course stresses the functional anatomy
      of the brain, especially the brainstem, in a format that is directly transferable
      to the clinical setting. These approaches include (1) using a small neurology
      book as one of the required texts in the course; (2) extensive use of magnetic
      resonance imaging (MRI) and computed tomography (CT) as an integral part of the
      instructional approach; (3) teaching external and internal anatomy of the brain,
      particularly the brainstem and spinal cord, in a "clinical orientation" that
      reflects how these central nervous system (CNS) regions are viewed in the
      clinical setting; (4) teaching nuclei and tracts in images of stained sections
      and correlating this information with comparable MRI and CT images; and (5) using
      a large series (75 images) of vascular drawings and clinical cases, all in
      clinical orientation. The clinical applicability of the basic science
      information, therefore, is continuously reinforced and extended. It is suggested
      that teaching anatomy and anatomical concepts in formats that are more obviously
      useful in, and applicable to, the clinical setting will enhance the value of this
      basic science in the medical curriculum.

PMID- 12001217
TI  - Integrated approach to teaching and testing in histology with real and virtual
      imaging.
AB  - The University of Iowa College of Medicine histology teaching laboratory
      incorporates extensive Web- and computer-based teaching modalities, including the
      Virtual Microscope (VM), as emerging learning aids in histology and pathology
      laboratory instruction. We report here our experience in offering a multiple
      resource-based approach to laboratory instruction while retaining the opportunity
      and requirement of examining actual microscopic slide preparations with the
      microscope. Acceptance of this approach has been high among our students and
      faculty, and performance levels established over years of teaching histology by
      traditional means have been maintained.

PMID- 12001218
TI  - Innovative testing method for an integrated radiology-histology curriculum.
AB  - A module of radiology instruction was incorporated into an existing histology
      course for first-year medical students (n = 177). An innovative testing
      methodology for assessing the instructional effectiveness of the integrated
      radiology-histology module was developed and tested. Test items were designed to
      measure the students' ability to integrate the two disciplines successfully.
      Radiologic and histologic images were displayed at each of seven stations, to
      which the content of the images either were or were not related. The seven
      stations were incorporated into three traditional histology laboratory
      examinations. For purposes of data analysis, each test was divided into three
      components, including histology alone, histology in combination, and radiology in
      combination. Testing lengths were equated using the Spearman-Brown statistical
      adjustment. Analysis of the test results showed the reliability coefficients to
      be comparable to the traditional testing methods used previously in the course.
      Correct responses were similar in all three sections, ranging between 85 to 97%.
      This methodology thus appears to be an effective means of testing an integrated
      curriculum.

PMID- 12001219
TI  - Survey of gross anatomy, microscopic anatomy, neuroscience, and embryology
      courses in medical school curricula in the United States.
AB  - Directors of courses in the basic anatomical sciences in allopathic and
      osteopathic medical schools in the United States were surveyed regarding the
      present composition of their courses. Results indicate the majority of gross
      anatomy courses are in the range of 126 to 200 total course hours, and that
      laboratory dissection is a key component of these courses. The majority of
      microscopic anatomy courses are in the range of 61 to 100 total course hours,
      generally divided equally between lecture and laboratory components.
      Additionally, despite the availability of computer technology, microscopes are
      still used in the vast majority of microscopic anatomy courses. The majority of
      neuroscience courses are in the range of 71 to 90 total course hours, with most
      of these hours devoted to lectures. Embryology is usually taught in conjunction
      with gross anatomy, although some schools present it with the microscopic anatomy
      course or as a separate course. Most embryology courses are in the range of 6 to
      20 total course hours, with only a few having a laboratory component.

PMID- 12001221
TI  - Principles of docking: An overview of search algorithms and a guide to scoring
      functions.
AB  - The docking field has come of age. The time is ripe to present the principles of
      docking, reviewing the current state of the field. Two reasons are largely
      responsible for the maturity of the computational docking area. First, the early
      optimism that the very presence of the "correct" native conformation within the
      list of predicted docked conformations signals a near solution to the docking
      problem, has been replaced by the stark realization of the extreme difficulty of
      the next scoring/ranking step. Second, in the last couple of years more realistic
      approaches to handling molecular flexibility in docking schemes have emerged. As
      in folding, these derive from concepts abstracted from statistical mechanics,
      namely, populations. Docking and folding are interrelated. From the purely
      physical standpoint, binding and folding are analogous processes, with similar
      underlying principles. Computationally, the tools developed for docking will be
      tremendously useful for folding. For large, multidomain proteins, domain docking
      is probably the only rational way, mimicking the hierarchical nature of protein
      folding. The complexity of the problem is huge. Here we divide the computational
      docking problem into its two separate components. As in folding, solving the
      docking problem involves efficient search (and matching) algorithms, which cover
      the relevant conformational space, and selective scoring functions, which are
      both efficient and effectively discriminate between native and non-native
      solutions. It is universally recognized that docking of drugs is immensely
      important. However, protein-protein docking is equally so, relating to
      recognition, cellular pathways, and macromolecular assemblies. Proteins function
      when they are bound to other molecules. Consequently, we present the review from
      both the computational and the biological points of view. Although large, it
      covers only partially the extensive body of literature, relating to small (drug)
      and to large protein-protein molecule docking, to rigid and to flexible.
      Unfortunately, when reviewing these, a major difficulty in assessing the results
      is the non-uniformity in the formats in which they are presented in the
      literature. Consequently, we further propose a way to rectify it here.

PMID- 12001222
TI  - Modeling of protein interactions in genomes.

PMID- 12001220
TI  - Approaches to studying cellular signaling: a primer for morphologists.
AB  - Many research projects will lead to understanding tissue and/or cell responses to
      extracellular influences either from soluble factors or the surrounding
      extracellular matrix. These types of investigations will require the
      understanding of signal transduction. This particular cell biological field has
      literally exploded with information and new technical approaches in the past 10
      years. This article is directed toward investigators interested in using these
      new approaches to study their systems. An overview of the general principles of
      signal transduction events including the types of receptors and intracellular
      signaling events is followed by an introduction to methods for visualizing signal
      transduction. This is followed by an introduction to biochemical analysis and an
      example of combining several approaches to understanding a tissue response to
      extracellular matrix stimulus.

PMID- 12001223
TI  - Time-resolved backbone desolvation and mutational hot spots in folding proteins.
AB  - A method is presented to identify hot mutational spots and predict the extent of
      surface burial at the transition state relative to the native fold in two-state
      folding proteins. The method is based on ab initio simulations of folding
      histories in which transitions between coarsely defined conformations and
      pairwise interactions are dependent on the solvent environments created by the
      chain. The highly conserved mammalian ubiquitin is adopted as a study case to
      make predictions. The evolution in time of the chain topology suggests a
      nucleation process with a critical point signaled by a sudden quenching of
      structural fluctuations. The occurrence of this nucleus is shown to be concurrent
      with a sudden escalation in the number of three-body correlations whereby
      hydrophobic units approach residue pairs engaged in amide-carbonyl hydrogen
      bonding. These correlations determine a pattern designed to structure the
      surrounding solvent, protecting intramolecular hydrogen bonds from water attack.
      Such correlations are shown to be required to stabilize the nucleus, with kinetic
      consequences for the folding process. Those nuclear residues that adopt the dual
      role of protecting and being protected while engaged in hydrogen bonds are
      predicted to be the hottest mutational spots. Some such residues are shown not to
      retain the same protecting role in the native fold. This kinetic treatment of
      folding nucleation is independently validated vis-a-vis a Phi-value analysis on
      chymotrypsin inhibitor 2, a protein for which extensive mutational data exists.

PMID- 12001224
TI  - Conformational polymorphism of wild-type and mutant prion proteins: Energy
      landscape analysis.
AB  - Conformational transitions are thought to be the prime mechanism of prion
      diseases. In this study, the energy landscapes of a wild-type prion protein (PrP)
      and the D178N and E200K mutant proteins were mapped, enabling the
      characterization of the normal isoforms (PrP(C)) and partially unfolded isoforms
      (PrP(PU)) of the three prion protein analogs. It was found that the three energy
      landscapes differ in three respects: (i) the relative stability of the PrP(C) and
      the PrP(PU) states, (ii) the transition pathways from PrP(C) to PrP(PU), and
      (iii) the relative stability of the three helices in the PrP(C) state. In
      particular, it was found that although helix 1 (residues 144-156) is the most
      stable helix in wild-type PrP, its stability is dramatically reduced by both
      mutations. This destabilization is due to changes in the charge distribution that
      affects the internal salt bridges responsible for the greater stability of this
      helix in wild-type PrP. Although both mutations result in similar destabilization
      of helix 1, they a have different effect on the overall stability of PrP(C) and
      of PrP(PU) isoforms and on structural properties. The destabilization of helix 1
      by mutations provides additional evidences to the role of this helix in the
      pathogenic transition from the PrP(C) to the pathogenic isoform PrP(SC).

PMID- 12001225
TI  - Simulating proteins at constant pH: An approach combining molecular dynamics and
      Monte Carlo simulation.
AB  - For the structure and function of proteins, the pH of the solution is one of the
      determining parameters. Current molecular dynamics (MD) simulations account for
      the solution pH only in a limited way by keeping each titratable site in a chosen
      protonation state. We present an algorithm that generates trajectories at a
      Boltzmann distributed ensemble of protonation states by a combination of MD and
      Monte Carlo (MC) simulation. The algorithm is useful for pH-dependent structural
      studies and to investigate in detail the titration behavior of proteins. The
      method is tested on the acidic residues of the protein hen egg white lysozyme. It
      is shown that small structural changes may have a big effect on the pK(A) values
      of titratable residues.

PMID- 12001226
TI  - M13 endopeptidases: New conserved motifs correlated with structure, and
      simultaneous phylogenetic occurrence of PHEX and the bony fish.
AB  - M13 endopeptidase alignments have focused mainly on mammalian sequences and on
      the active site region defining the catalytic sequence signatures. Aligning all
      available M13 from bacteria to human on a full-length basis, we have performed a
      sequence analysis. This enabled us to highlight the origin and function of the
      M13 PHEX subtype family endopeptidase (phosphate regulating gene with homologies
      to endopeptidases on the X chromosome). New evolutionary conserved regions in
      both prokaryotes and eukaryotes have been detected and eukaryotic-specific
      regions clearly delineated. Using the recently solved neprilysin structure, we
      have observed that all new motifs, except one, localize in the spatial vicinity
      of the previously reported catalytic signatures. Interestingly, a highly
      hydrophobic pocket containing three newly reported motifs is centered by the C
      terminal tryptophan residue. Extensive M13 searches in complete and in progress
      higher eukaryotic genomes have lead to the identification of Danio rerio as the
      simplest organism having PHEX. Finally, the human PHEX substrate, the parathyroid
      hormone-related peptide, PTHrP(107-139), is absent in bony fish: this suggests
      the existence of further PHEX substrates common to both bony fishes and higher
      vertebrates.

PMID- 12001227
TI  - Ab initio prediction of protein structure using LINUS.
AB  - LINUS is an ab initio method for the prediction of protein structure based on
      simple physical principles. Here we report the performance of LINUS at CASP4, a
      community wide experiment to predict protein structure in which participants are
      blinded to the structures they seek to predict. We submitted 13 predictions for
      this experiment. The best four are described in detail, together with an
      assessment of secondary structure prediction for the entire set. Coordinates for
      all predictions are available from the CASP web site
      (http://predictioncenter.llnl.gov). It should be emphasized that our use of the
      descriptor "ab initio" is unequivocal: the sole input into these simulations is
      the amino acid sequence.

PMID- 12001228
TI  - Protein sequence threading: Averaging over structures.
AB  - Multiple sequence alignments are a routine tool in protein fold recognition, but
      multiple structure alignments are computationally less cooperative. This work
      describes a method for protein sequence threading and sequence-to-structure
      alignments that uses multiple aligned structures, the aim being to improve models
      from protein threading calculations. Sequences are aligned into a field due to
      corresponding sites in homologous proteins. On the basis of a test set of more
      than 570 protein pairs, the procedure does improve alignment quality, although no
      more than averaging over sequences. For the force field tested, the benefit of
      structure averaging is smaller than that of adding sequence similarity terms or a
      contribution from secondary structure predictions. Although there is a
      significant improvement in the quality of sequence-to-structure alignments, this
      does not directly translate to an immediate improvement in fold recognition
      capability.

PMID- 12001229
TI  - Emergence of highly designable protein-backbone conformations in an off-lattice
      model.
AB  - Despite the variety of protein sizes, shapes, and backbone configurations found
      in nature, the design of novel protein folds remains an open problem. Within
      simple lattice models it has been shown that all structures are not equally
      suitable for design. Rather, certain structures are distinguished by unusually
      high designability: the number of amino acid sequences for which they represent
      the unique lowest energy state; sequences associated with such structures possess
      both robustness to mutation and thermodynamic stability. Here we report that
      highly designable backbone conformations also emerge in a realistic off-lattice
      model. The highly designable conformations of a chain of 23 amino acids are
      identified and found to be remarkably insensitive to model parameters. Although
      some of these conformations correspond closely to known natural protein folds,
      such as the zinc finger and the helix-turn-helix motifs, others do not resemble
      known folds and may be candidates for novel fold design.

PMID- 12001230
TI  - Flexibility in monomeric Cu,Zn superoxide dismutase detected by limited
      proteolysis and molecular dynamics simulation.
AB  - Limited proteolysis by trypsin of monomeric Cu,Zn superoxide dismutase from
      Escherichia coli induces a specific cleavage of the polypeptide chain at the
      level of Lys60 located in the S-S subloop of loop 6,5 where, when compared to the
      eukaryotic enzyme, a seven-residues insertion, completely exposed to the solvent,
      is observed. This result suggests that this subloop is disordered and flexible,
      thus enabling binding and adaptation to the active site of the proteolytic
      enzyme. Indeed, molecular dynamics simulation indicates that the S-S subloop
      undergoes high fluctuations and that its high flexibility coupled to an high
      solvent accessibility can explain the specific bond selection of the protease. As
      a matter of fact, of the possible 14 solvent accessible proteolytic sites only
      the Lys60 flexible site is cleaved. High flexibility and solvent exposure are
      confirmed by the short water residence time for the residues corresponding to the
      cleavage site evaluated by molecular dynamics simulation. These experiments
      demonstrate that molecular dynamics simulation and limited proteolysis are
      complementary and unambiguous tools to identify flexible sites in proteins.

PMID- 12001231
TI  - ConsDock: A new program for the consensus analysis of protein-ligand
      interactions.
AB  - Protein-based virtual screening of chemical libraries is a powerful technique for
      identifying new molecules that may interact with a macromolecular target of
      interest. Because of docking and scoring limitations, it is more difficult to
      apply as a lead optimization method because it requires that the docking/scoring
      tool is able to propose as few solutions as possible and all of them with a very
      good accuracy for both the protein-bound orientation and the conformation of the
      ligand. In the present study, we present a consensus docking approach (ConsDock)
      that takes advantage of three widely used docking tools (Dock, FlexX, and Gold).
      The consensus analysis of all possible poses generated by several docking tools
      is performed sequentially in four steps: (i) hierarchical clustering of all poses
      generated by a docking tool into families represented by a leader; (ii)
      definition of all consensus pairs from leaders generated by different docking
      programs; (iii) clustering of consensus pairs into classes, represented by a mean
      structure; and (iv) ranking the different means starting from the most populated
      class of consensus pairs. When applied to a test set of 100 protein-ligand
      complexes from the Protein Data Bank, ConsDock significantly outperforms single
      docking with respect to the docking accuracy of the top-ranked pose. In 60% of
      the cases investigated here, ConsDock was able to rank as top solution a pose
      within 2 A RMSD of the X-ray structure. It can be applied as a postprocessing
      filter to either single- or multiple-docking programs to prioritize three
      dimensional guided lead optimization from the most likely docking solution.

PMID- 12001232
TI  - Water in protein cavities: A procedure to identify internal water and exchange
      pathways and application to fatty acid-binding protein.
AB  - A computational approach based on Delaunay triangulation is presented to identify
      internal water molecules in proteins and to capture pathways of exchange with the
      bulk. The implemented procedure is computationally efficient and can easily be
      applied to long molecular dynamics trajectories of protein simulations. In an
      application to fatty acid-binding protein in apo-form and with bound palmitate,
      several protein orifices known from crystal structures have been confirmed to be
      major portals of solvent exchange. Differences between the two forms of the
      protein are observed and discussed.

PMID- 12001233
TI  - Solution structure and backbone dynamics of an antigen-free heavy chain variable
      domain (VHH) from Llama.
AB  - Camelids, (dromedaries, camels, and llamas) produce heavy-chains antibodies, with
      their antigen recognition sites composed of a single VH-like domain, referred to
      as VHH. The solution structure of one of these VHHs domains (VHH-H14), raised
      against the alpha subunit of the human chorionic gonadotropin hormone (hCG), has
      been determined by (15)N heteronuclear three-dimensional NMR spectroscopy. The
      framework is well resolved within the set of 20 best-calculated NMR structures
      and is close to that of classical VH domains from vertebrate antibodies,
      consisting of two antiparallel beta-sheets organized in a beta-barrel. Loops
      display a lower precision, especially the Complementarity Determining Regions
      (CDRs), involved in antigen recognition. Comparison of the three-dimensional VHH
      H14 solution structure with its previously solved crystal structure (Spinelli et
      al., Nature Struct. Biol. 1996;3:752-757) reveals a high similarity to the
      framework, whereas significant conformational differences occur on CDRs, leading
      to the assumption that the antigen recognition site is a more mobile part. In
      order to deepen our insights into the dynamics of VHH-H14 in solution, (15)N
      relaxation was measured with longitudinal R1 and transverse R2 self-relaxation
      rates, and (15)N steady-state heteronuclear nuclear Overhauser enhancements
      (NOE), making it possible to probe picosecond-to-millisecond internal motions.
      Determination of dynamic parameters (S(2), tau(e), and Rex) through the Lipari
      Szabo Model-free approach enables the identification of several regions with
      enhanced dynamics. Especially, the mobility measurements from NMR confirm that
      the antigen recognition site is the most mobile part of the VHH-H14 domain on
      picosecond-to-nanosecond fast time scales. Several residues belonging to the
      three CDRs are submitted to chemical exchange processes occurring on slow
      microsecond-to-millisecond time scales, suggesting that the formation of the
      VHH/antigen complex should be accompanied by structural changes.

PMID- 12001234
TI  - X-ray structure of Mycobacterium tuberculosis nucleoside diphosphate kinase.

PMID- 12001235
TI  - Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers
      sensitivity to mecillinam.

PMID- 12001236
TI  - Crystal structure of the Escherichia coli glucose-inhibited division protein B
      (GidB) reveals a methyltransferase fold.

PMID- 12001237
TI  - Crystal structure of the Streptococcus pneumoniae phosphomevalonate kinase, a
      member of the GHMP kinase superfamily.

PMID- 12001238
TI  - NMR structure of the hypothetical protein encoded by the YjbJ gene from
      Escherichia coli.

PMID- 12001239
TI  - Three-dimensional macroporous calcium phosphate bioceramics with nested chitosan
      sponges for load-bearing bone implants.
AB  - Three-dimensional macroporous calcium phosphate bioceramics embedded with porous
      chitosan sponges were synthesized to produce composite scaffolds with high
      mechanical strength and a large surface/volume ratio for load-bearing bone
      repairing and substitutes. The macroporous calcium phosphate bioceramics with
      pore diameters of 300 microm to 600 microm were developed using a porogen burnout
      technique, and the chitosan sponges were formed inside the pores of the
      bioceramics by first introducing chiosan solution into the pores followed by a
      freeze-drying process. Our scanning electron microscopy results showed that the
      pore size of chitosan sponges formed inside the macroporous structure of
      bioceramics was approximately 100 microm, a structure favorable for bone tissue
      in-growth. The compressive modulus and yield stress of the composite scaffolds
      were both greatly improved in comparison with that of HA/beta-TCP scaffolds. The
      simulated body fluid (SBF) and cell culture experiments were conducted to assess
      the bioactivity and biocompatibility of the scaffolds. In the SBF tests, a layer
      of randomly oriented needle-like apatite crystals formed on the scaffold surface
      after sample immersion in SBF, which suggested that the composite material has
      good bioactivity. The cell culture experiments showed that MG63 osteoblast cells
      attached to the composite scaffolds, proliferated on the scaffold surface, and
      migrated onto the pore walls, indicating good cell biocompatibility of the
      scaffold. The cell differentiation on the composite scaffolds was evaluated by
      alkaline phosphatase (ALP) assay. Compared with the control in tissue culture
      dishes, the cells had almost the same ALP activity on the composite scaffolds
      during the first 11 days of culture.

PMID- 12001240
TI  - Trabecular bone response to injectable calcium phosphate (Ca-P) cement.
AB  - The aim of this study was to investigate the physicochemical, biological, and
      handling properties of a new developed calcium phosphate (Ca-P) cement when
      implanted in trabecular bone. Ca-P cement consisting of a powder and a liquid
      phase was implanted as a paste into femoral trabecular bone of goats for 3 days
      and 2, 8, 16, and 24 weeks. The cement was tested using three clinically relevant
      liquid-to-powder ratios. Polymethylmethacrylate bone cement, routinely used in
      orthopedics, was used as a control. The Ca-P cement was easy to handle and was
      fast setting with good cohesion when in contact with body fluids. X-ray
      diffraction at the different implantation periods showed that the cement had set
      as an apatite and remained stable over time. Histological evaluation after 2
      weeks, performed on 10 microm un-decalcified sections, showed abundant bone
      apposition on the cement surface without any inflammatory reaction or fibrous
      encapsulation. At later time points, the Ca-P cement implants were totally
      covered by a thin layer of bone. Osteoclast-like cells, as present at the
      interface, had resorbed parts of the cement mass. At locations where Ca-P cement
      was resorbed, new bone was formed without loss of integrity between the bone bed
      and the cement. This demonstrated the osteotransductive property of the cement,
      i.e., resorption of the material by osteoclast-like cells, directly followed by
      the formation of new bone. Histological and histomorphometrical evaluation did
      not show any significant differences between the Ca-P cement implanted at the
      three different liquid/powder ratios. The results indicate that the investigated
      Ca-P cement is biocompatible, osteoconductive, as well as osteotransductive and
      is a candidate material for use as a bone substitute.

PMID- 12001241
TI  - Absorbable sandwich-like membrane for retinal-sheet transplantation.
AB  - Neural retinal transplantation has great potential for the alleviation of
      different degenerative and hereditary retinal disorders. However, because of the
      fragile and soft nature of retina, retinal-sheet transplantation is relatively
      difficult to achieve. To overcome this difficulty, we developed a technique for
      lamellar tissue transplantation. Biodegradable gelatin membranes were fabricated
      into a sandwich and encapsulated retinal grafts for transplantation. Before
      transplantation, we characterized the in vivo and in vitro properties of such
      membranes to determine the optimal sterilization procedure, that is, a sterile
      membrane with suitable degradability and good mechanical properties and without
      cytotoxicity. Three sterilization methods were conducted, with hydrogen peroxide
      gas plasma (HPGP), ethylene oxide (EO), and gamma-ray irradiation (gamma). The
      results were compared with those of a control (no disinfection). Initial studies
      revealed that the gelatin membranes sterilized with HPGP or EO exhibited retinal
      pigment epithelium (RPE) cytotoxicity, whereas the membrane sterilized by 16.6
      kGy gamma ray irradiation had no RPE cytotoxicity and had enhanced mechanical
      properties. In the in vivo rabbit study, implanted gelatin membranes demonstrated
      satisfactory biocompatibility without any inflammation. Transplanted retinal
      sheets survived well and developed laminar structures. Such a method using
      gelatin membranes for tissue transportation has great potential for future
      routine retinal-sheet transplantation.

PMID- 12001242
TI  - Bacterial adhesion onto azidated poly(vinyl chloride) surfaces.
AB  - A plasticized poly(vinyl chloride) surface was modified by azidation using sodium
      azide in the presence of a phase transfer catalyst in aqueous media. Subsequent
      to azidation, the surface was crosslinked using ultraviolet radiation. Contact
      angle measurements showed that the surface became hydrophilic on azidation
      whereas photoirradiation did not have any further effect on the hydrophilicity of
      the azidated surface. Control, azidated, and photocrosslinked surfaces were
      exposed to two strains of bacteria commonly implicated in device infection such
      as Staphylococcus aureus and Escherichia coli. Whereas the control and
      photocrosslinked surfaces showed no significant difference in bacterial adhesion,
      the azidated surface showed significantly reduced adhesion to both strains. Data
      obtained indicate that the presence of an intact azide function on the polymer
      surface is responsible for the reduced bacterial adherence and the surface
      hydrophobicity/hydrophilicity did not exert any effect in the present case.
      Although azides are known to be effective only against Gram-negative species,
      surprising was the observation that the azidated polymer surface was equally
      effective against a Gram-positive species such as S. aureus. Because sodium azide
      is routinely used as a preservative to prevent bacterial and fungal growth in
      many microbiology reagents and diagnostic kits, covalent binding of the azide
      onto a polymer surface or synthesizing azide containing polymers may be an
      interesting method to investigate in tackling the problem of bacterial adhesion
      and colonization of medical devices.

PMID- 12001243
TI  - Transmission electron microscopic visualization of the degradation and
      phagocytosis of a poly-L-lactide screw in cancellous bone: a long-term
      experimental study.
AB  - The increasing clinical use of biodegradable implants in orthopedic surgery makes
      it necessary to determine their long-term behavior in tissues. In this study, a
      biodegradable screw made of poly-L-lactide (PLLA) was inserted axially into the
      right distal femur in 18 rabbits. The degradation and phagocytosis process of
      PLLA was assessed histologically and by transmission electron microscopy (TEM).
      The follow-up times were 3 and 4.5 years for groups of nine and eight animals,
      respectively. Abundant birefringent polymeric material was still present in the
      center of the implant channel in all specimens in both follow-up groups. The PLLA
      material studied appeared to be a biologically relatively inert material, with
      only sparse reactive cellular activity at the tissue-implant boundary. In the TEM
      specimens, polymeric particles of an average area of 2 microm2 were seen to be
      located intracellularly within phagocytic cells. The spheric and polygonal
      particles were membrane-bound and to a great extent filled up each phagocyte. In
      the 4.5-year specimens, the size of the polymeric particles, measured as area and
      perimeter, was significantly smaller (p < 0.02) than that of the 3-year
      specimens. The findings indicate that the ultimate degradation process of PLLA is
      much longer than it previously was thought to be. Complete degradation probably
      still would have taken years after the 4.5-year span of this study.

PMID- 12001244
TI  - Dentin proteoglycans: an immunocytochemical FEISEM study.
AB  - Dentin proteoglycans are fundamental constituents of the dentin matrix and are
      distributed ubiquitously both in dentin and cement. They have several important
      functional properties; in particular, they have a fundamental role in the
      maintenance and the correct stabilization of collagen fibers. The use of
      phosphoric acid on dentin, as proposed in most common dental adhesive systems to
      establish a reliable bond, may affect the molecular structure of proteoglycans.
      The aim of this study was to evaluate, after the application of EDTA or
      phosphoric acid on dentin, the dentin proteoglycans with an immunocytochemical
      approach with high resolution SEM. For this purpose, dentin disks obtained from
      recently extracted human molars were etched with a 35% water solution of
      phosphoric acid for 15 s, 30 s, and 60 s. Control specimens were conditioned with
      EDTA. Specimens were immunolabeled with a monoclonal antibody antichondroitin
      sulfate and visualized with a gold-conjugated secondary antibody. Conditioning
      dentin with EDTA resulted in a distinct labeling of the proteoglycans, as
      visualized on branching fibrillar structures in the order of 10-20 nm. The use of
      35% phosphoric acid on dentin revealed a coagulation of proteoglycans after
      etching for 15 s while a very low labeling signal was detectable after 30 s. No
      labeling was obtained after etching dentin with phosphoric acid for 60 s. These
      results suggest that the use of 35% phosphoric acid on dentin is able to produce
      significant structural modifications of the dentin proteoglycans even after short
      application times. Additionally, when applied on the dentin surface for more than
      30 s, phosphoric acid produces a dramatic decrease in proteoglycans'
      antigenicity, probably due to structural modifications of the three-dimensional
      conformation of these molecules.

PMID- 12001245
TI  - Histopathologic reaction of a calcium phosphate cement for alveolar ridge
      augmentation.
AB  - The objective of the present study was to evaluate the feasibility of using a
      calcium phosphate cement (CPC) in the reconstruction of a defective alveolar
      ridge in conjunction with implant placement. The CPC consisted of an equimolar
      amount of tetracalcium phosphate and dicalcium phosphate anhydrous. At the
      beginning of the experiment, all mandibular premolar teeth of mature beagle dogs
      were extracted. After 1 month of healing, alveolar bone was reduced to make a
      space for a CPC block that was prefabricated from a CPC mixed with water at a
      powder/liquid ratio of 5 g/mL. After an additional month, 8-mm long
      hydroxyapatite-coated titanium implants were placed in such a way that the apical
      half was embedded into alveolar bone and the coronal half in the preformed CPC
      block. The dogs were sacrificed and biopsies were obtained at 1, 3, and 6 months
      after surgery. Sections that included implants were evaluated for integration of
      the CPC block to the alveolar bone and of the implant to the alveolar bone.
      Additional sections without the implants served as controls. The results obtained
      from this study show that the CPC ridge augmentation gradually is replaced by
      natural bone. Six months after surgery, histopathologic features of the
      augmentation area were quite similar to those of natural alveolar bone. The
      coronal half of the implants, previously surrounded by the CPC block, was firmly
      fixed by natural bone. Therefore, this method may be useful for increasing the
      height of the alveolar ridge.

PMID- 12001246
TI  - Liquid photocurable biodegradable copolymers: in vivo degradation of photocured
      poly(epsilon-caprolactone-co-trimethylene carbonate).
AB  - Liquid photoreactive poly(epsilon-caprolactone-co-trimethylene carbonate)s
      endcapped with a coumarin group [coumarinated poly(CL/TMC)s] were prepared using
      tetra-functional hydroxylated substances such as pentaerythritol or four-branched
      poly(ethylene glycol), b-PEG. These coumarinated copolymers are tetra-branched
      and exist as a viscous liquid (MW 5 x10(3) approximately 7 x 10(3)). They were
      photocured by ultraviolet (UV) light irradiation to obtain a swelling or
      nonswelling solid under water, depending on the type of initiator used. The
      resultant films were implanted into the subcutaneous tissues of rats for up to 5
      months. The photocured b-PEG-based copolymer was completely degraded and sorbed
      within a 1 month. On the other hand, surface-eroding degradation of
      pentaerythritol-based, coumarinated poly(CL/TMC) progressed with implantation
      time, and minimal recruitment of neutrophils, macrophages, and multinucleated
      giant cells was observed over the implantation period. Among the pentaerythritol
      based copolymers, the fastest surface erosion was observed for the copolymer with
      the highest epsilon-caprolactone content. Microfabricated films with microarrays
      in which photoconstructs were stereolithographically prepared, using three
      different coumarinated copolymers at different regions, showed that upon
      implantation there was regionally differentiated biodegradation of microarrays,
      and the degree of region-specific biodegradation depended on the type of
      photocured copolymer. The observed tendency for biodegradation was in good
      agreement with that observed during implantation of individual films in vivo.
      This study also demonstrates that the use of multi-material-arrayed films enables
      the determination of different responses in vivo using only one sample.

PMID- 12001247
TI  - Experimental studies on bone induction using low-molecular-weight poly (DL
      lactide-co-glycolide) as a carrier for recombinant human bone morphogenetic
      protein-2.
AB  - An appropriate carrier acting as a slow delivery vehicle for the BMPs is required
      for maximal clinical effectiveness of these bone-inductive proteins. The purpose
      of this study was to evaluate a low-molecular-weight PLGA copolymer as a
      synthetic, biodegradable carrier for rhBMP-2 implantation in vivo. Two, 10, or 50
      microg of recombinant human BMP-2 were mixed with 10 mg of a poly (DL-lactide-co
      glycolide) (PLGA) 50:50 copolymer and implanted into the calf muscles of Wistar
      rats. Soft X-ray analysis and histologic examination indicated that new bone
      formation occurred at all rhBMP-2-implanted sites within 3 weeks after
      implantation. Correlation of rhBMP-2 concentration with the amount of bone
      induction was confirmed by specific alkaline phosphatase activity and calcium
      content assay. In vitro analysis indicated that 78.5% of the PLGA copolymer was
      degraded to smaller molecular weight material after 14 days in PBS solution. It
      is suggested that rhBMP-2 was released in an active form at the implant site
      during the degradation of the copolymer, resulting in the induction of new bone
      formation. Thus this low-molecular-weight PLGA copolymer material represents a
      promising delivery vehicle for BMPs, and possibly other growth factors, around
      dental and orthopedic implants.

PMID- 12001248
TI  - Self-curing acrylic formulations containing PMMA/PCL composites: properties and
      antibiotic release behavior.
AB  - Partially biodegradable acrylic composites containing poly(methyl methacrylate)
      poly(epsilon-caprolactone) (PMMA/PCL) systems were prepared by mixing the
      corresponding PMMA/PCL beads (89:11, 86:14, 83:17, and 77:23 weight ratio) used
      as solid phase with methyl methacrylate (MMA) (liquid phase) in a solid/liquid
      ratio of 1.5:1. The physical and chemical microheterogeneity of these beads
      influenced significantly the curing parameters, because several aspects involved
      in the polymerization reaction are closely related to both morphology and size
      distribution of the particles. In vitro behavior was studied by immersion in
      simulated body fluid at pH = 7.4 and 37 degrees C for more than 8 weeks and the
      composition was followed by 1H-nuclear magnetic resonance spectroscopy.
      Approximately 2% wt/wt weight loss was observed after a period of 8 weeks for the
      composites richest in PCL. Mechanical properties of the dry and wet specimens
      were evaluated by compressive and tensile tests. In all cases, the presence of
      PCL in the composites provided a significant decrease in both compressive
      strength and elastic modulus compared with plain PMMA. Tensile and compressive
      strength also decreased significantly after 2 weeks of immersion in simulated
      body fluid compared with dry specimens. The self-curing composites based on
      PMMA/PCL beads and loaded with 3% wt/wt vancomycin were evaluated as carriers for
      local release of antibiotics. The composite prepared with beads of PMMA/PCL ratio
      86:14 was the most effective. It eluted 64% of the initial drug within the first
      5 h, allowing progressive release of nearly the total amount of the initial drug
      (90%) in approximately 2 months. The results obtained suggest that the described
      composites can be suitable for antibiotic release in non-load bearing graft
      applications.

PMID- 12001249
TI  - Chondroinduction of mouse mesenchymal stem cells in three-dimensional highly
      porous matrix scaffolds.
AB  - Porous polyvinyl formal (PVF) resin and poly(lactide-caprolactone) [P(LA/CL)]
      sponges were examined as three-dimensional matrices for chondroinduction of
      cultured bone marrow mesenchymal stem cells (MSCs). Approximately 5 x 10(5) mouse
      MSCs were seeded in porous PVF resin or P(LA/CL) sponges and were cultured for up
      to 1 month in serum-free high-glucose Dulbecco's modified Eagle's medium
      containing 10 ng/mL transforming growth factor-beta3 and 100 nM dexamethasone for
      chondroinduction. After the 1-month culture period, the PVF resin and P(LA/CL)
      sponges contained approximately twice the amount of glycosaminoglycans compared
      with the control pellet. Safranin-O staining of PVF and P(LA/CL) after 1 month of
      culture revealed a cartilage-like extracellular matrix containing
      glycosaminoglycans and collagen. When implanted into nude mice, PVF and P(LA/CL)
      seeded with MSCs were found to be both biocompatible and chondroinductive. These
      highly porous scaffolds can maintain a large number of cells in a three
      dimensional structure. Both are potentially promising for the chondroinduction of
      bone marrow MSCs for research and clinical applications.

PMID- 12001250
TI  - Improved sample preparation of biomaterials for in vitro genotoxicity testing
      using reference materials.
AB  - New biomaterial related reference materials with known genotoxic properties were
      produced in order to study the sample preparation and in vitro genotoxicity
      testing of biomaterials. We incorporated genotoxic substances like benzo[a]pyrene
      into the biomaterial Tecoflex, a polyurethane frequently used for catheters and
      other applications. We demonstrated that the model compound benzo[a]pyrene is
      sufficiently extracted by organic solvents, whereas cell culture medium only
      extracts very limited quantities. By changing the medium several times during
      extraction the extracted amount was augmented. Using higher amounts of organic
      solvent in relation to the reference material's surface led to a higher recovery
      of extracted benzo[a]pyrene. For the in vitro genotoxicity testing using the
      Mammalian Cell Gene Mutation Test (HPRT test), Mammalian Chromosome Aberration
      Test, and bacterial umu- and SOS-tests, concentration of extracts is a
      prerequisite because of the low sensitivity of the test systems. Often
      cytotoxicity interferes with the evaluation of genotoxic effects. We demonstrated
      that some recommendations of the ISO 10993-Part 3 and 12,(1),(2) dealing with the
      biological evaluation of medical devices, seem to be insufficient, and new rules
      for the in vitro genotoxicity testing of biomaterials have to be established.

PMID- 12001251
TI  - Soft-tissue response to silicone and poly-L-lactic acid implants with a periodic
      or random surface micropattern.
AB  - Tissue reaction to biomaterials is dependent on properties such as surface
      topography. The aim of this study was to evaluate the tissue reaction around
      implants with different surface topographies. We made coin-shaped silicone and
      poly-L-lactic acid (PLLA) implants with double-sided parallel microgrooves (depth
      1.0 microm; width 10.0 microm) and random roughness on a micrometer scale. The
      control implants were smooth. These implants were inserted into subcutaneous
      pockets created on the flanks of goats. After 1, 3, or 12 weeks, the goats were
      sacrificed and the implants retrieved and histologically processed. Light
      microscopic evaluation revealed the formation of fibrous tissue capsules around
      all implant materials. The PLLA did not visibly degrade during the study period.
      Histomorphometric analyses were performed on capsule thickness, capsule quality,
      and on the implant-tissue interface quality. Compared with the silicone implants,
      the capsules around the PLLA implants showed significantly better capsule
      quality. Compared to the smooth implants, the capsules around the microgrooved
      implants were thicker, but the capsules around the roughened implants were
      thinner. However, randomly roughened implant surfaces generally elicited a
      stronger and more prolonged inflammatory reaction compared to smooth and
      microgrooved implant surfaces. We conclude that the application of microgrooves
      or random surface roughness to polymer implants apparently does not have
      beneficial effects on peri-implant tissue healing.

PMID- 12001252
TI  - In vitro mineralization of a glass-ceramic of the MgO-3CaO x P2O5-SiO2 system:
      wettability studies.
AB  - The calcium phosphate deposition on the surface of a bioactive glass-ceramic of
      the MgO-3CaO. P(2)O(5)-SiO(2) system during a 1-week immersion in biological
      model fluids, was investigated through wettability studies. Two model fluids with
      chemical composition similar to the human blood plasma were tested: Hanks'
      balanced salt solution (HBSS) and a simulated body fluid (SBF) with a higher
      calcium content. The effect of the presence of albumin, both in solution or
      previously adsorbed to the surface, was assessed. The behavior observed using two
      SBF solutions prepared with and without TRIS buffer was compared. The surface
      free energy of the glass-ceramic samples was determined, before and after
      immersion, and dynamic contact angle analysis was performed using the biological
      model fluids as scanning liquids. Scanning electron microscope observations and x
      ray photoelectron spectroscopy (XPS) analysis were performed to complement the
      wettability studies. The experimental results led to the conclusion that the
      precipitation of a calcium phosphate film in HBSS occurred mainly when the
      immersion solution was renewed daily or in the presence of adsorbed albumin. In
      SBF, the addition of TRIS buffer seemed to inhibit the formation of the calcium
      phosphate film.

PMID- 12001253
TI  - Synthesis of macroporous hydroxyapatite scaffolds for bone tissue engineering.
AB  - A novel method of preparing macroporous hydroxyapatite (HA) by dual-phase mixing
      was developed: HA slurry and Polymethylmethacrylate (PMMA) resin were mixed
      together at the volume ratio of 1:1. After pyrolytic removal of the PMMA phase,
      HA with an open porous structure was obtained. In this way, the porosity of the
      ceramic was limited to 50%. Attempts to increase the porosity by adding more PMMA
      resin were confronted with the technical hurdle of sample collapse during the
      pyrolysis process. To increase the porosity and to improve pore interconnection,
      an extra foaming step was introduced before the polymerization of PMMA resin.
      Three foaming agent systems were tried, based on the reactions of citric acid and
      (bi)carbonate salts: sodium bicarbonate, calcium carbonate, and ammonium
      bicarbonate. Although all the three foaming agents were able to increase the
      porosity up to 70%, keeping all the pores interconnected throughout, only
      ammonium bicarbonate system turned out to be applicable to make HA scaffolds or
      implants, because both NaHCO(3) and CaCO(3) systems caused alkalic residues in
      the final ceramic. The porous HA samples were fully characterized by FTIR, XRD,
      ESEM (EDX), and optical microscopy.

PMID- 12001254
TI  - Cytotoxicity of glutaraldehyde crosslinked collagen/poly(vinyl alcohol) films is
      by the mechanism of apoptosis.
AB  - Collagen has been investigated as a potential natural biomaterial, because of its
      occurrence in the extracellular matrix. Collagen requires crosslinking in this
      context, by reagents that are often cytotoxic. Glutaraldehyde is one such agent
      that is potentially cytotoxic. The aim of this study was to determine the cause
      of poor cell attachment and growth on collagen/poly(vinyl alcohol) bioartificial
      composite films, when crosslinked with glutaraldehyde. Dehydrothermal
      crosslinking was used as a comparison. Human osteoblasts were observed to undergo
      apoptosis on glutaraldehyde crosslinked films dependent on concentration of
      collagen present. Higher collagen content resulted in higher levels of apoptosis
      with poor cell attachment and spreading of remaining cells. Post-treatment of
      films with 8% L-glutamic acid prevented the apoptotic response of osteoblasts and
      allowed attachment and spreading. The addition of 100 nM insulin-like growth
      factor-1 to the culture medium also prevented apoptosis. Glutaraldehyde toxicity
      of crosslinked collagen has been demonstrated in this study, the mechanism of
      which is apoptosis. This study indicates that poor biocompatibility and induction
      of apoptosis on collagen/poly(vinyl alcohol) films crosslinked by glutaraldehyde
      are attributed to glutaraldehyde components on the surface of the films (not
      residual glutaraldehyde), whose effects can be quenched by glutamic acid, and
      prevented by insulin-like growth factor-1.

PMID- 12001255
TI  - Effect of perforations in burr hole covers on cranial bone regeneration in
      rabbits.
AB  - The reconstruction of bone defects is a significant problem in cranio
      maxillofacial surgery. In an effort to avoid the known disadvantages of
      autogenous bone grafting, alternatives have been investigated. Bone substitute
      materials, degradable or nondegradable, aim at facilitating bone regeneration,
      while they take over load-bearing functions for a period of time. In this study,
      the healing of cranial defects in rabbits was assessed using polylactide guiding
      covers with and without perforations. Bilateral circular cranial defects were
      produced in 16 New Zealand white rabbits. The defects were covered with extruded
      and laser cut polylactide burr hole covers, each animal receiving a perforated
      burr hole cover on one side and a nonperforated one on the contralateral side.
      Bone seeking fluorochromes were administered at regular intervals. After an
      observation period of 8 weeks the amount of bone regeneration in the area of the
      defects was quantified from contact radiographs, and the dynamics of bone
      formation were assessed by fluorescence microscopy. Stained sections were used to
      analyze morphologic differences. No signs of adverse tissue reactions or
      osteolysis were observed. A bone-guiding function was observed for both covers
      with or without perforations. Intracranial tissue herniation into the defect
      hindered the regeneration process. Wide intraindividual and interindividual
      variation became apparent and average defect filling was only 40% within the 8
      week observation period. In this model the perforated covers offered no advantage
      over nonperforated covers. It can be concluded from this study, that the use of
      external burr hole covers alone does not guarantee a full thickness regeneration
      of the cranial defect, but it provides a guiding function for promotion of
      structured bone regeneration.

PMID- 12001256
TI  - Mechanical and morphological study of biostable polyurethane heart valve leaflets
      explanted from sheep.
AB  - Two novel biostable polyurethanes, designated EV3.34 and EV3.35, were used to
      manufacture a flexible trileaflet heart valve. The valves were implanted in the
      mitral position in young adult (18 month) sheep. Six valves were electively
      explanted at 6 months and the remaining six valves at 9 months follow-up. The
      leaflet material was examined by surface Fourier transform infrared spectrometry
      (ATR/FTIR) and scanning electron microscopy (SEM). The leaflet material was also
      subjected to cyclic mechanical testing and, compared with unimplanted control
      material, to demonstrate any change in mechanical properties during implantation.
      There was no degradation of functional groups detected by ATR/FTIR, although
      there was a slight surface enrichment of siloxane soft segment. Surface
      morphology of the explanted leaflet material was similar to unimplanted control
      material. EV3.34 demonstrated similar inelastic energy loss behavior, with no
      significant change in residual strain in explanted compared with control
      material. EV3.35 demonstrated a reduction in inelastic energy and residual strain
      in explanted compared with control material. There is no evidence of
      biodegradation of these siloxane-based polyurethanes, in functional valves up to
      9 months implantation in sheep. The FTIR and SEM findings are supported by the
      retention of mechanical properties of the materials.

PMID- 12001257
TI  - Synthesis of pH-sensitive inulin hydrogels and characterization of their swelling
      properties.
AB  - In this study, pH-responsive inulin hydrogels were prepared by radical
      copolymerization of methacrylated inulin (MA-inulin) with acrylic acid (AAc) in
      aqueous solution using ammonium peroxydisulfate (APS) and N,N,N',N'
      tetramethylethylenediamine (TMEDA) as an initiation system. The AAc content in
      hydrogels was evaluated by FTIR spectroscopy. The covalent bridging of AAc among
      MA moieties of MA-inulins was observed by a significant increase in the effective
      network density of hydrogels and further confirmed by TGA studies. While, at a
      low content of AAc, the hydration of hydrogels at pH 7.4 decreased owing to the
      increased crosslinking density, the swelling subsequently increased with further
      increasing AAc as a consequence of the increased ionic osmotic pressure within
      hydrogels. The change in swelling of hydrogels in response to pH change between
      7.4 and 2.2 was therefore enlarged when the AAc content increased.

PMID- 12001258
TI  - Detection of microscopic cracks in dental ceramic materials by fluorescent
      penetrant method.
AB  - Ceramic materials are used as implants and prostheses because of their excellent
      biocompatibility and in the dental field beyond that, because of esthetic
      advantages and the little plaque accumulation. A disadvantage is their
      sensitivity to microscopic cracks because of their brittleness. Strength
      deteriorating microscopic cracks can be introduced into the ceramic surface by
      the manufacturing process. The objective of this study was to evaluate three
      methods on their efficiency to detect microscopic surface cracks of clinical
      relevance in dental ceramic materials. These methods were light-optical
      microscopy, fluorescent microscopy after penetration with a fluorescent liquid,
      and scanning electron microscopy (SEM). It was found that microscopic cracks of
      critical sizes can be detected using the fluorescent penetrant method, which was
      not to be proven by light-optical microscopy and even not by SEM. We conclude
      from our study that the fluorescent penetrant method could help to decrease
      clinical failures of dental ceramic components that are caused by surface
      microscopic cracks from the manufacturing process, if this method was routinely
      performed before the clinical use of the ceramic components.

PMID- 12001259
TI  - In vitro degradation and fracture toughness of multilayered porous poly(propylene
      fumarate)/beta-tricalcium phosphate scaffolds.
AB  - This study investigated the in vitro degradation of poly(propylene fumarate)/beta
      tricalcium phosphate (PPF/beta-TCP) scaffolds in pH 7.4 phosphate-buffered saline
      at 37 degrees C. Scaffold design consisted of three layers: two solid layers
      about a central layer of porous PPF foam. Solid PPF with molecular weights of 810
      and 1450 Da was crosslinked under UV light. PPF foam was prepared by a
      photocrosslinking, porogen-leaching method with an initial porogen content of 80
      wt % and two sizes, 150-300 and 300-500 microm. Comparison of initial and
      residual weights demonstrated a 14.3 +/- 2.0% loss of mass at 3 weeks and a 16.6
      +/- 1.8% loss of mass at 6 weeks. Observed pH values for all constructs remained
      stable (7.15-7.40) throughout the 3 to 6 weeks. Scanning electron micrographs of
      these scaffolds revealed some loss of foam material between 3 and 6 weeks;
      however, foam microarchitecture was intact. Solid PPF fracture toughness was
      tested for high and low molecular weight PPF, 0.376 +/- 0.004 and 0.134 +/- 0.015
      MPa(m)1/2, respectively. These values are roughly one magnitude less than human
      cortical bone.

PMID- 12001260
TI  - Biomaterial implants induce the inflammation marker CRP at the site of
      implantation.
AB  - Following implantation of biomaterial patches into the gastrointestinal tract, we
      analyzed the host's response towards the foreign material. Asymmetric patches of
      polydioxanone covered Vicryl or poly-3-hydroxybutyrate were sutured onto the rat
      stomach. Tissue samples were generated at distinct time intervals after surgery,
      and RNA profiles were compared by Differential Display. RT-PCR analysis of gene
      candidates that seemed differentially expressed showed that vitamin D binding
      protein mRNA was induced in stomach tissue after implantation of the biomaterial
      patches. In parallel, the amount of C-reactive protein mRNA was found to be
      increased transiently as well. Implants induce a tissue response that is specific
      for a given material.

PMID- 12001261
TI  - Building the house around the plumbing.
AB  - Signaling between growing blood vessels and the tissues that they innervate has
      traditionally been viewed as a one-way conversation, with organs and tissues
      supplying important cues for the growth and anatomical patterning of the blood
      vessels supplying them, but not vice-versa. Two recent papers now provide
      evidence that blood vessels can have an important role in promoting the assembly
      of organs and tissues. These papers show that proper formation of the pancreas
      and liver and induction of endocrine and hepatic cell types in these endodermal
      organs requires inductive signals from blood vessels.

PMID- 12001262
TI  - GAPs in Slit-Robo signaling.
AB  - Neuronal migration requires the integration of a number of diverse environmental
      cues and subsequent translation to specific responses such as directed
      cytoskeletal remodeling. Accurate knowledge of the signal transduction pathways
      linking activation of surface receptors to actin dynamics is necessary in order
      to understand the regulation of such processes. Activation of the Roundabout
      (Robo) receptor mediates a repulsive response in certain pioneering axons and
      migratory neurons. Recently, Wong et al have described a signaling link between
      Robo activation and specific GTPase activity that appears to regulate neuronal
      migration. A novel family of GTPase regulators, responsive to Slit-Robo
      engagement, has been identified and convincingly shown to alter the migration of
      neuronal cells. This study not only delineates a specific signaling route from
      guidance receptors to directed neuronal movement, but also offers clues towards
      potential regulatory mechanisms that ensure specificity of the Slit-Robo
      response.

PMID- 12001263
TI  - Notching up another pathway.
AB  - The Notch proteins play a vital role in cell fate decisions in both invertebrate
      and vertebrate development. Careful analysis of this role has led to a model of
      signalling downstream of these receptors, via the CSL (CBF1, Suppressor of
      Hairless, Lag-1) family of transcription factors. There have been suggestions,
      however, that Notch can signal through other pathways. In the current paper,
      Ramain et al. provide compelling evidence for Notch signalling through a CSL
      independent pathway and they demonstrate that the cytoplasmic protein, Deltex, is
      required for this signal. In addition, they show that Wnt signalling may regulate
      this Deltex-dependent signal.

PMID- 12001264
TI  - The role of DNA replication in chromosome condensation.
AB  - At metaphase, DNA in a human chromosome is estimated to be compacted at least
      10,000 fold in length. However, the higher order mechanisms by which the
      chromosomes are organized in interphase and subsequently further condensed in
      mitosis have largely remained elusive. One generally overlooked participant in
      chromosome condensation is DNA replication. Many early studies of eukaryotic
      chromosome organization and cell fusions have suggested that DNA replication
      plays a role in chromosome compaction. Recent phenotypic analysis of Drosophila
      DNA replication mutants has revitalized this old idea. In this review, the role
      of DNA replication in chromosome condensation will be examined.

PMID- 12001265
TI  - Unraveling the mechanisms of the vertebrate circadian clock: zebrafish may light
      the way.
AB  - Most organisms display oscillations of approximately 24 hours in their
      physiology. In higher organisms, these circadian oscillations in biochemical and
      physiological processes ultimately control complex behavioral rhythms that allow
      an organism to thrive in its natural habitat. Daily and seasonal light cycles are
      mainly responsible for keeping the circadian system properly aligned with the
      environment. The molecular mechanisms responsible for the control of the
      circadian clock have been explored in a number of systems. Interestingly, the
      circadian oscillations that are responsive to environmental stimuli are present
      very early during development. This review focuses on the advantages of using the
      zebrafish to study the development of the vertebrate circadian system and light
      dependent signaling to the clock.

PMID- 12001266
TI  - Stabilizing the regionalisation of the developing vertebrate central nervous
      system.
AB  - During embryonic development, a number of tissues are patterned by their
      subdivision into domains with distinct regional identity. An important question
      is how sharp interfaces are established and maintained between adjacent domains
      despite the potential for scrambling due to cell intermingling during tissue
      growth. Two mechanisms have been found to underlie the maintenance of sharp
      interfaces: the specific restriction of cell mixing across boundaries, or the
      switching of identity of cells that cross between domains. We review the evidence
      for these mechanisms at distinct boundaries in the developing vertebrate central
      nervous system, and discuss what is known about their molecular mediators.

PMID- 12001267
TI  - Molecular biology of Fanconi anaemia--an old problem, a new insight.
AB  - Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting
      from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE,
      FANCF and FANCG). Although caused by relatively simple mutations, the disease
      shows a complex phenotype, with a variety of features including developmental
      abnormalities and ultimately severe anaemia and/or leukemia leading to death in
      the mid teens. Since 1992 all but two of the genes have been identified, and
      molecular analysis of their products has revealed a complex mode of action. Many
      of the proteins form a nuclear multisubunit complex that appears to be involved
      in the repair of double-strand DNA breaks. Additionally, at least one of the
      proteins, FANCC, influences apoptotic pathways in response to oxidative damage.
      Further analysis of the FANC proteins will provide vital information on normal
      cell responses to damage and allow therapeutic strategies to be developed that
      will hopefully supplant bone marrow transplantation.

PMID- 12001268
TI  - Molecular genetics of sexual development in the mushroom Coprinus cinereus.
AB  - Sexual development in the mushroom Coprinus cinereus is under the control of two
      mating type loci, A and B. When two haploid homokaryons with compatible alleles
      at both A and B loci are mated, the coordinated activities of A- and B-regulated
      pathways lead to formation of a mycelium termed the dikaryon, in which the two
      nuclei from the mating partners pair in each cell without fusing. The dikaryon is
      a prolonged mycelial stage that can be induced to develop a multicellular
      structure, the mushroom, under proper environmental conditions. The two nuclei
      fuse in specialized cells on the mushroom and immediately undergo meiosis to
      complete the sexual life cycle. It has been established recently that the A genes
      encode two classes of homeodomain proteins while the B genes encode pheromones
      and their receptors. More recently, molecular genetics has been used to reveal
      genes that work downstream of the mating type genes to regulate dikaryon
      formation, mushroom morphogenesis, and meiosis.

PMID- 12001269
TI  - Branching, segmentation and the metapterygial axis: pattern versus process in the
      vertebrate limb.
AB  - Explanations of the patterns of vertebrate fin and limb evolution are improving
      as specific hypotheses based on molecular and developmental data are proposed and
      tested. Comparative analyses of gene expression patterns and functions in
      developing limbs, and morphological patterns in embryonic, adult and fossil limbs
      point to digit specification as a key developmental innovation associated with
      the origin of tetrapods. Digit development during the fin-to-limb transition
      involved sustained proximodistal outgrowth and a new phase of Hox gene expression
      in the distal fin bud. These patterning changes in the distal limb have been
      explained by the linked concepts of the metapterygial axis and the digital arch.
      These have been proposed to account for the generation of limb pattern by
      sequential branching and segmentation of precartilagenous elements along the
      proximodistal axis of the limb. While these ideas have been very fruitful, they
      have become increasingly difficult to reconcile with experimental and comparative
      studies of fin and limb development. Here we argue that limb development does not
      involve a branching mechanism, and reassess the concept of a metapterygial axis
      in limb development and evolution.

PMID- 12001270
TI  - Is there a code for protein-DNA recognition? Probab(ilistical)ly. . .
AB  - Transcriptional regulation of all genes is initiated by the specific binding of
      regulatory proteins called transcription factors to specific sites on DNA called
      promoter regions. Transcription factors employ a variety of mechanisms to
      recognise their DNA target sites. In the last few decades, attempts have been
      made to describe these mechanisms by general sets of rules and associated models.
      We give an overview of these models, starting with a historical review of the
      somewhat controversial issue of a "recognition code" governing protein-DNA
      interaction. We then present a probabilistic framework in which advantages and
      disadvantages of various models can be discussed. Finally, we conclude that
      simplifying assumptions about additivity of interactions are sufficiently
      justified in many situations (and can be suitably extended in other situations)
      to allow a unifying concept of a "probabilistic code" for protein-DNA recognition
      to be defined.

PMID- 12001271
TI  - Role of the sarcoplasmic reticulum in smooth muscle.

PMID- 12001272
TI  - Effects of deep inhalations on bronchial reactivity in pediatric asthma.

PMID- 12001273
TI  - Respiratory impedance response to a deep inhalation in children with history of
      cough or asthma.
AB  - The aim of this study was to describe the change in respiratory impedance induced
      by a deep inhalation (DI) in children who developed a positive response to
      inhalation of methacholine (Mch). Eighteen children aged 4.5-12.5 years,
      presenting with chronic cough or doctor-diagnosed asthma, were studied at
      baseline after inhalation of Mch and after inhalation of a bronchodilator.
      Respiratory resistance (Rrs) and reactance (Xrs) were measured by the forced
      oscillation technique, varying transrespiratory pressure at 12 Hz around the
      head. The tidal flow (V') and volume (V) dependence of Rrs before and after the
      DI was characterized according to the equation Rrs = K1 + K2 x /V'/ + K3 x V. DI
      induced no significant change at baseline or after inhalation of a bonchodilator.
      During Mch challenge, Rrs and K1 were significantly lower, and K3 and Xrs
      significantly less negative after DI than before, during both inspiration and
      expiration; there was no change in K2. We conclude that DI results in a decrease
      in Rrs in children with induced bronchoconstriction. The associated changes in
      Xrs, K1, and K3, and lack of decrease in K2, suggest that dilatation of airways
      occurs at the bronchial level, with little contribution of the upper airways or
      of a change in breathing patterns.

PMID- 12001274
TI  - Exploring the relationship between forced maximal flow at functional residual
      capacity and parameters of forced expiration from raised lung volume in healthy
      infants.
AB  - The raised volume rapid thoraco-abdominal compression technique (RVRTC) is being
      increasingly used to assess airway function in infants, but as yet no consensus
      exists regarding the equipment, methods, or analysis of recorded data. The aim of
      this study was to explore the relationship between maximal flow at functional
      residual capacity (V'(maxFRC)) and parameters derived from raised lung volumes,
      and to address analytical aspects of the latter technique in an attempt to assist
      with future standardization initiatives. Forced vital capacity (FVC) from lung
      volume raised to 3 kPa, timed forced expiratory volumes (FEV(t)), and forced
      expiratory flow parameters at different percentages of expired FVC (FEF(%)) were
      measured in 98 healthy infants (1-69 weeks of age). V'(maxFRC) using the tidal
      rapid thoraco-abdominal compression (RTC) technique was also measured. The within
      subject relationships and within-subject variability of the various parameters
      were assessed. Duration of forced expiration was < 0.5 sec in 5 infants, meaning
      that FEV(0.3) and FEV(0.4) were the only timed volume parameters that could be
      calculated in all infants during the first months of life, and even when it could
      be calculated, FEV(0.5) approached FVC in many of these infants. It is
      recommended that FEV(0.4) be routinely reported in infants less than 3 months of
      age. Contrary to previous reports, within subject variability of V'(maxFRC) was
      less than that of FEF(75) (mean CV = 6.3% and 8.9%, respectively).A more
      standardized protocol when analyzing data from the RVRTC would facilitate
      comparisons of results between centers in the future.

PMID- 12001275
TI  - Attenuation of pressure swings along the endotracheal tube is indicative of
      optimal distending pressure during high-frequency oscillatory ventilation in a
      model of acute lung injury.
AB  - We tested the hypothesis that during high-frequency oscillatory ventilation, the
      oscillatory pressure ratio (OPR) is minimal at the optimal mean airway pressure
      (Paw). OPR is defined as the ratio of pressure swings at the distal end and the
      proximal opening of the endotracheal tube. Optimal Paw was assumed to be the
      lowest Paw at which the physiological shunt fraction was below 0.1. Acute lung
      injury was produced by saline lung lavage of pigs who were then subjected to a
      stepwise increase of Paw to impose underinflation, optimal inflation, and
      overdistention (inflation phase), followed by a stepwise decrease of Paw
      (deflation phase). OPR reached a minimum of 0.10 +/- 0.01 at Paw = 31 +/- 4 cm
      H(2)O during the inflation phase and a minimum of 0.04 +/- 0.01 at Paw = 18 +/- 1
      cm H(2)O during the deflation phase. Optimal Paw was 31 +/- 4 cm H(2)O on the
      inflation limb and 14 +/- 2 cm H(2)O on the deflation limb. Paw at the minimal
      OPR was not significantly different from the optimal Paw during the inflation
      phase, and slightly but significantly higher (4.1 +/- 1.6 cm H(2)O) during the
      deflation phase. In conclusion, a consistent relationship was found between OPR
      and Paw, with a minimum in all animals. The minimal OPR coincides fairly well
      with the Paw where oxygenation is optimal.

PMID- 12001276
TI  - Type I nitric oxide synthase is decreased in the fetal pulmonary circulation of
      hypertensive lambs.
AB  - The nitric oxide (NO)/guanosine 3',5'-cyclic monophosphate (cGMP) pathway plays
      an essential role in mediating pulmonary vasodilatation during transition of the
      pulmonary circulation at birth. We used immunoblot analysis (Western) and
      semiquantitative immunohistochemistry to study the presence, distribution, and
      relative amounts of type I nitric oxide synthase (NOS-I). Immunoblots were
      performed on normal fetal sheep lungs, whereas immunohistochemistry for NOS-I was
      compared between lungs from normal fetal lambs vs. fetal lambs with persistent
      pulmonary hypertension of the newborn (PPHN) induced by ligation of the ductus
      arteriosus. Western blot analysis using a polyclonal antibody detected NOS-I
      protein in homogenates of normal fetal sheep lungs. Abundant NOS-I
      immunoreactivity was observed exclusively in the precapillary resistance vessels,
      i.e., terminal bronchiole-associated arteries (TA) and respiratory bronchiole
      associated arteries (RA) in normal fetal lung. In marked contrast,
      immunoreactivity for NOS-I was significantly reduced in the TA and RA of
      hypertensive lungs. We conclude that there is a heterogeneous distribution of NOS
      I in the normal fetal sheep lung, but that NOS-I staining is significantly
      reduced in lambs with PPHN.

PMID- 12001277
TI  - Differential effect of dexamethasone and hydrocortisone on alveolar growth in rat
      pups.
AB  - Glucocorticoids are widely used in perinatology, since they decrease the
      incidence of respiratory distress syndrome and chronic lung disease. However,
      evidence is now increasing that their use in this age group may result in
      impaired alveolar lung growth and general development. The aim of this study was
      to determine whether a low dose of hydrocortisone (1 mg/kg/day for 11 days) was
      deleterious to lung growth in rat pups, as compared to an equivalent dose of
      dexamethasone. While both dexamethasone and hydrocortisone increased alveolar
      diameter with thinning of the interairspace walls, only dexamethasone reduced the
      overall internal surface area of the lung available for respiratory exchange.
      Changes were more marked with dexamethasone as compared to hydrocortisone, which
      did not appear to affect alveolar septation. In conclusion, a prolonged course of
      low-dose hydrocortisone may be deleterious for alveolar lung growth in rat pups,
      but the changes are less marked than those caused by dexamethasone.

PMID- 12001278
TI  - Cytokines in severe respiratory syncytial virus bronchiolitis.
AB  - Bronchiolitis caused by respiratory syncytial virus (RSV) infection is an
      important cause of severe lung disease in infants, and increasing evidence
      suggests that it is immunologically mediated. Experiments in mice suggest that
      this may be due to differential T-cell activation producing either type 1 or type
      2 cytokines. We investigated this hypothesis in man by studying 24 infants
      ventilated with severe RSV bronchiolitis and by measuring messenger RNA (mRNA)
      for interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), by polymerase chain
      reaction, in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL)
      fluids. A semiquantitative assay was used to estimate concentrations of mRNA for
      these cytokines in comparison to mRNA of the constitutively expressed
      hypoxanthine guanine phosphoribosyl transferase gene. BAL from 18/24 infants
      showed polarization of cytokine production: 6 with only IFN-gamma mRNA, and 12
      with only IL-4 mRNA. For the 6/24 infants in whom both IL-4 mRNA and IFN-gamma
      mRNA were detected in BAL fluid, each was present in low amounts, compared with
      those with mRNA for IL-4 or IFN-gamma alone. IL-4 and IFN-gamma mRNA were not
      detected in any of the NPAs.These findings provide the first direct evidence in
      infants that in RSV bronchiolitis there are divergent T-cell responses and
      suggest that more than one mechanism may be responsible for immune-mediated
      disease enhancement.

PMID- 12001279
TI  - Prediction of duration of hospitalization in respiratory syncytial virus
      infection.
AB  - Identification of variables that predict duration of RSV-associated
      hospitalization may be useful in the identification of preventive and therapeutic
      strategies. A recently published prediction model (Michigan model) for the
      duration of hospitalization in RSV infection demonstrated good discrimination
      between children with and without an increased likelihood of a hospital stay >or=
      7 days, based on variables such as log weight, congenital heart disease, failure
      to thrive, premature birth, bronchopulmonary dysplasia, other pulmonary diseases,
      miscellaneous conditions, early mechanical ventilation, and early ribavirin
      treatment (receiver operating characteristic (ROC) area, 0.89). Validation of
      this model is of particular interest for Europe, since the mean duration of
      hospitalization in The Netherlands is approximately twice that in the USA. The
      objective of the current study was 1) to validate the Michigan model for RSV
      hospitalized patients in a large university hospital in The Netherlands, and 2)
      to develop our own prediction model for a prolonged hospital stay. Data from 177
      children younger than 12 months of age admitted with confirmed RSV infection to
      the Sophia Children's Hospital Rotterdam between 1992-1995, were used for
      valiation of the Michigan model and derivation of the Rotterdam model. Mean
      duration of hospitalization for the Rotterdam database was 10.3 (+/-6.3) days,
      with a median of 9 days; 138 (78%) patients had a hospital stay >or= 7 days. The
      Michigan model performed poorly when applied to the Rotterdam database, with an
      ROC area of 0.65 (95% CI, 0.57-0.73). The Rotterdam prediction model (hospital
      stay >or= 9 days, the median in our database) considered weight and need for
      oxygen supplementation. The ROC area was 0.65 (95% CI, 0.57-0.73). When using
      data from patients for the 1995-1996 season, the ROC area was 0.52 (95% CI, 0.34
      0.72). The Michigan and the Rotterdam models failed to identify a considerable
      number of patients who had a prolonged hospital stay, with a low false-positive
      rate. We conclude that neither the Michigan, nor the Rotterdam model reliably
      predicted the duration of hospitalization based on demographic and clinical
      variables.

PMID- 12001280
TI  - Prevalence of respiratory syncytial virus infection in Italian infants
      hospitalized for acute lower respiratory tract infections, and association
      between respiratory syncytial virus infection risk factors and disease severity.
AB  - This study was designed to collect data on the prevalence of respiratory
      syncytial virus (RSV) infection in Italy in infants hospitalized for lower
      respiratory tract infections, and to evaluate which of the recognized risk
      factors might be associated with disease severity. Thirty-two centers throughout
      Italy participated in the study. Over a 6-month period (November 1,1999 to April
      30, 2000), we evaluated all children < 2 years of age hospitalized for lower
      respiratory tract infections. All subjects were tested for RSV within 24 hr of
      hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack,
      RSV). Logistic regression was used to identify the factors that might be
      associated with more severe disease or could increase the likelihood of RSV
      positivity in hospitalized infants. Out of a total of 1,232 children enrolled,
      40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred
      in February, while the lowest prevalence of RSV positivity was seen in November
      (P < 0.05). A high proportion of study subjects had low birth weight and low
      gestational age. The clinical diagnosis at hospitalization was bronchiolitis in
      66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis
      group, a higher prevalence of RSV+ was found in patients with gestational age
      <or= 33 weeks or 34-35 weeks, as compared to those with a gestational age >or= 36
      weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in
      the three gestational age subgroups with pneumonia and wheezy bronchitis (P >
      0.05, each comparison). Independent of the clinical diagnosis at admission, RSV
      infection was associated with more severe respiratory impairment. Environmental
      smoke exposure was higher in subjects with bronchiolitis than in those with
      wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth
      order (P < 0.05). The presence of older siblings and birth order plays an
      important role in RSV infection. The collected data show that, in Italy, RSV is
      an important cause of lower respiratory tract infection in infants. Gestational
      age, birth order, birth weight, and exposure to tobacco smoke affected the
      prevalence and severity of RSV-related lower respiratory tract disease.

PMID- 12001281
TI  - Histology of childhood bronchiolitis obliterans.
AB  - Childhood bronchiolitis obliterans (CBO) is an uncommon disease characterized by
      persistent signs and symptoms of obstructive respiratory disease after an acute
      bronchiolar injury. It is considered to be a complication of viral infection,
      most often of adenovirus, and is usually classified as a constrictive-type
      bronchiolitis obliterans (BO). Few reports have described its histology. We
      present the histopathological features of 34 pediatric patients with a diagnosis
      of BO, comprising 30 open lung biopsies (OLB), 2 lobectomies, and 2 autopsies.
      Quantitative analysis was performed on the OLB to better characterize the
      morphological changes observed in these lungs. Of 37 patients, 25 were male and 9
      were female, ranging from 7 months to 15 years of age. Airway diameter in
      terminal bronchioles varied from 50-600 microm. Ninety-seven percent of the CBO
      were of constrictive type, with variable degrees of airway obstruction. Chronic
      inflammation in the bronchioles was mild in 63% of the patients. Aggregates of
      foamy macrophages, mucostasis, and bronchiectasis appeared in, respectively, 93%,
      40%, and 30% of the biopsies. There was more hyperinflation than atelectasis
      (40.1% and 24.3%, respectively). Lobectomies and autopsies showed more severe
      bronchiolar obliteration, associated with bronchiectasis. The results show that
      CBO is characterized histologically mainly by a constrictive pattern, with
      variable degrees of inflammation and airway obliteration. Secondary signs of
      airway obstruction are invariably present. Mild histological changes may
      predominate and should be carefully evaluated by the pathologist.

PMID- 12001282
TI  - Relationship between sputum inflammatory markers, lung function, and lung
      pathology on high-resolution computed tomography in children with cystic
      fibrosis.
AB  - High-resolution computed tomography (HRCT) is a sensitive technique for early
      visualisation and location of cystic fibrosis (CF) bronchopathology, and has been
      shown to detect acute reversible and chronic changes. It would be expected to
      correlate with markers of the underlying pathological processes, such as sputum
      cytokines and cytology, as well as with pulmonary function tests (PFTs). Our aim
      was to study the relationship between PFTs, sputum cytology, and sputum cytokine
      interleukin-8 (IL-8) and HRCT in CF patients. Prospective standardized collection
      of sputum samples was performed at the time of routine annual high-resolution CT
      scans. Forced expired volume in 1 sec (FEV(1)) and forced vital capacity (FVC)
      were recorded. Sputum processing was selective, with dispersal by the three
      enzyme technique. IL-8 measurements were by kit assay. HRCT scans were scored by
      a pediatric radiologist, blinded to clinical condition, using a modified Bhalla
      score.Forty-three CT scans were performed on 34 children with CF between March
      1998 and April 2000. Mean age was 12.3 years (range, 6-21 years), FEV(1) (%
      predicted) was 67% (range, 23-120%), and mean modified Bhalla score was 11.2
      (range, 0-22). Sputum IL-8 concentration (mean, 86; range, 4-150 ng/mL) and total
      cell count (mean, 31.9 x 10(6)/mL; range, 21.8-42.0 x 10(6)/mL) were high. FEV(1)
      and FVC correlated with modified Bhalla score (r = -0.66, P < 0.0001 for both),
      and most individual components of the score, especially mosaic perfusion (r = 
      0.64, r = -0.61 respectively, P < 0.0001) and extent of bronchiectasis (r = 
      0.61, P < 0.0001 for both). The combination of these two predicted 58% of the
      variability in FEV(1) on analysis of variance (P < 0.0001). Sputum total cell
      count correlated weakly with modified Bhalla score (r = 0.38, P < 0.05) and with
      FEV(1) and FVC (r = -0.36, P < 0.05; and r = -0.46, P < 0.01). Differential cell
      counts, cell viability, and IL-8 did not correlate with modified Bhalla scores,
      or with reversible components such as mucus plugging, centrilobular nodules, or
      peribronchial thickening. In conclusion, pathological changes on HRCT correlated
      with lung function but not with sputum markers of inflammation.

PMID- 12001283
TI  - Predictors of deterioration of lung function in cystic fibrosis.
AB  - The severity of lung disease in cystic fibrosis (CF) may be related to the type
      of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene, and to environmental and immunological factors. Since pulmonary disease is
      the main determinant of morbidity and mortality in CF, it is important to
      identify factors that can explain and predict this variation. The aim of this
      longitudinal study of the whole Swedish CF population over age 7 years was to
      correlate genetic and clinical data with the rate of decline in pulmonary
      function. The statistical analysis was performed using the mixed model regression
      method, supplemented with calculation of relative risks for severe lung disease
      in age cohorts.The severity of pulmonary disease was to some extent predicted by
      CFTR genotype. Furthermore, the present investigation is the first long-term
      study showing a significantly more rapid deterioration of lung function in
      patients with concomitant diabetes mellitus. Besides diabetes mellitus,
      pancreatic insufficiency and chronic Pseudomonas colonization were found to be
      negative predictors of pulmonary function. In contrast to several other reports,
      we found no significant differences in lung function between genders. Patients
      with pancreatic sufficiency have no or only a slight decline of lung function
      with age once treatment is started, but an early diagnosis in this group is
      desirable.

PMID- 12001284
TI  - Bronchiectasis in children: orphan disease or persistent problem?
AB  - More than a decade ago, bronchiectasis unrelated to cystic fibrosis was termed an
      "orphan disease", because it had become an uncommon clinical entity among
      children in the developed world. Bronchiectasis is more common among children in
      lower socioeconomic classes and in developing countries, presumably due to more
      frequent and recurrent respiratory infections, environmental airway irritants,
      poor immunization rates, and malnutrition. Reports from the Southern Pacific and
      from Alaska Native children reveal persistently high rates of childhood
      bronchiectasis. Better epidemiologic data throughout the world are needed to
      reassess the importance of this condition. The pathophysiology includes airway
      inflammation, mucus production, and regional airway obstruction, yet the reasons
      why some children develop bronchiectasis while other do not is unclear. The
      coexistence of asthma with bronchiectasis is associated with more severe disease,
      yet the impact of asthma therapy in children with both disorders has not been
      studied. Similarly, the pattern of antibiotic use for children with
      bronchiectasis varies by region with little data to justify one particular
      approach. It may be that public health measures aimed at improving living
      conditions for children and prevention of respiratory infections with antiviral
      vaccines will have more impact on childhood bronchiectasis than medical
      treatments in the future.

PMID- 12001285
TI  - Amphotericin B-induced hepatorenal failure in cystic fibrosis.
AB  - Although nephrotoxicity is a common and well-recognized side effect of
      amphotericin B, hepatotoxicity is rare. We report on a 9-year-old girl with
      cystic fibrosis who developed fulminant renal and hepatic dysfunction following a
      short course of intravenous amphotericin B for a suspected aspergillus infection,
      although she did not have clinical evidence of invasive aspergillosis. The
      toxicity became apparent after changing to liposomal amphotericin. This
      association of renal and hepatotoxicity with liposomal amphotericin B has not
      previously been reported in children.

PMID- 12001324
TI  - External intermittent pneumatic compression.

PMID- 12001286
TI  - Pulmonary eosinophilic vasculitis in a neonate with congenital chylothorax.
AB  - We report a case of congenital bilateral chylothorax, complicated by pulmonary
      eosinophilic vasculitis and transient eosinophilia. Excluding all known forms of
      eosinophilic pulmonary disease either histologically or clinically, possible
      mechanisms of its etiology are discussed. Treatment with corticosteroids was
      successful, and after a prolonged clinical course the patient recovered by age 2
      years.

PMID- 12001325
TI  - Intermittent pneumatic compression as an adjuvant therapy in venous ulcer
      disease.
AB  - Despite improvements in healing rates venous ulcer disease still carries
      significant morbidity and cost. Any therapy that further improves healing rates
      is worthy of consideration. The recognised effects of intermittent pneumatic
      compression (IPC) on both arterial and venous circulation suggest that its use
      may confer significant benefits to venous ulcer healing. This study investigates
      the potential additive effects of adjuvant IPC on the healing and subsequent
      prevention of venous ulcers. Some improvement in the rate of healing in venous
      ulcers is noted. These findings are set against a background of very high healing
      rates in both treatment and control groups. No benefit is seen to accrue if IPC
      is used as an adjuvant therapy to help prevent recurrence of ulcers although the
      study period is very short.

PMID- 12001326
TI  - Evaluation of intermittent pneumatic compression systems.
AB  - The operational characteristics of eight intermittent pneumatic compression
      systems were evaluated. Considerable differences between the pressure/time curves
      were found when different pumps were compared. The pressure attained in the
      garments varied from 6 to 124 mmHg and the rate of inflation from less than 1 to
      9 mmHg per second.

PMID- 12001327
TI  - The effects of intermittent pneumatic compression on the arterial and venous
      system of the lower limb: a review.
AB  - A better understanding of lower limb haemodynamics and the effects of
      intermittent pneumatic compression on the lower limb has led to an increasing
      awareness of the potential value of intermittent pneumatic compression in both
      venous and arterial disease. Intermittent pneumatic compression can be used in
      both the primary and secondary care settings, with its advantages being further
      enhanced by excellent patient compliance and very low rate of complications.
      Intermittent pneumatic compression has a proven role in the prophylaxis of deep
      vein thrombosis and there is some evidence that it is a useful adjunct in the
      management of venous ulcer disease. With laboratory and more recent clinical
      studies demonstrating augmentation of arterial inflow with intermittent pneumatic
      compression, its use in arterial diseases is being increasingly explored. Further
      studies are needed to define the precise role of intermittent pneumatic
      compression in arterial disease but any treatment regimen which reduces the need
      for referral or intervention in the claudicant or critically ischaemic limb will
      be a valuable addition to those managing arterial disease.

PMID- 12001328
TI  - Compression hosiery in the prevention and treatment of venous leg ulcers.
AB  - Graduated compression therapy is the recognised gold standard for the treatment
      of venous ulcers, usually in the form of four-layer bandaging. Unfortunately with
      some patients the bulkiness of the bandages leads to non-compliance. An
      alternative to bandaging could be the use of below-knee graduated compression
      hosiery. This article will review the purpose and function of compression hosiery
      including details of patient assessment, measurement and compliance issues. It
      will provide the basic principles that should enable nurses to successfully treat
      patients with venous ulceration using compression hosiery.

PMID- 12001329
TI  - The Pressure Sore Alleviation Project.

PMID- 12001330
TI  - OIG: new Medicare appeals process leaves much to be desired.

PMID- 12001331
TI  - PFS's role in improving business outcomes in rehabilitation services.

PMID- 12001332
TI  - How much do private practitioners contribute to animal welfare?

PMID- 12001333
TI  - An ethicist's commentary on the case of clients having trouble explaining
      euthanasia to their children.

PMID- 12001334
TI  - A time for bold action.

PMID- 12001335
TI  - Lungworm (Crenosoma vulpis) infection in dogs on Prince Edward Island.
AB  - Crenosoma vulpis is a nematode lungworm that is highly prevalent in the red fox
      population of Atlantic Canada. Dogs are susceptible to infection with clinical
      signs consisting primarily of a chronic cough. A recent report of C. vulpis
      infection in 3 dogs on Prince Edward Island prompted an investigation into the
      importance of this parasite as a cause of chronic respiratory disease in Island
      dogs. A general prevalence was determined through the necropsy of dogs euthanized
      at the local humane society. Lungs were removed and examined for parasites using
      a lung flush technique. Rectal feces was collected and examined for first-stage
      larvae using the Baermann technique and zinc sulfate centrifugal flotation. Ten
      of 310 dogs (3.2%) were positive with 0-35 worms (mean = 11.0 +/- 13.4)
      recovered. First-stage larvae of C. vulpis were recovered in the rectal feces of
      the one animal in which no worms were recovered on lung flush. A second survey
      was conducted examining fecal samples with the Baermann technique from afebrile
      dogs with presenting signs of chronic cough that had no history of recent
      anthelmintic treatment and showed no signs of cardiac disease, based on physical
      examination. Fifteen of 55 dogs examined (27.3%) were definitively diagnosed as
      C. vulpis-positive. All of the infected dogs were treated with fenbendazole (50
      mg/kg body weight, p.o. q24 h for 3-7 days). Clinical signs resolved in all of
      the dogs and fecal samples were negative 2-4 weeks posttreatment. It was
      concluded that C. vulpis infection was a significant cause of upper respiratory
      disease in dogs on Prince Edward Island and should be considered in all dogs with
      presenting signs of chronic cough.

PMID- 12001336
TI  - The associations of viral and mycoplasmal antibody titers with respiratory
      disease and weight gain in feedlot calves.
AB  - Blood samples from 32 groups of calves (n = 700) were taken on arrival and after
      28-35 days at the feedlot. Eleven groups were housed in feedlots in Ontario, and
      21 groups in feedlots in Alberta. Serum antibody titers to bovine viral diarrhea
      virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza virus type
      3 (PIV-3), infectious bovine rhinotracheitis virus (IBRV), Mycoplasma dispar and
      M. bovis, plus data on bovine corona virus (BCV) from a previous study were
      investigated for their association with the risk of bovine respiratory disease
      (BRD), and with 28-day weight change, both before and after controlling for
      titers to Pasteurella haemolytica and Haemophilus somnus. Exposure to IBRV and M.
      bovis was infrequent, and although exposure to PIV-3 was more common, none of
      these agents had important associations with BRD. Higher titers to BVDV, BRSV,
      and BCV on arrival were associated with reduced risks of BRD and increased weight
      gains. However, there was some variation in these relationships and higher
      arrival titers to BVDV and BRSV in a subset of the calves were associated with
      increased risks of BRD. Titer increases to BVDV were associated with a higher
      risk of BRD and lower weight gains. Titer increases to BRSV were not usually
      associated with the occurrence of BRD, but titer increases to BRSV in a subset of
      calves that were vaccinated against BRSV, on arrival, were associated with an
      elevated risk of BRD. Of all the agents studied, BVDV had the most consistent
      associations with elevated risk of BRD and lower weight gains. Higher BRSV
      arrival titers were related to lower risk of BRD and higher weight gains; in some
      instances titer increases to BRSV were associated with higher BRD risk. Higher
      titers to BCV on arrival were related to reduced risks of BRD. Practical ways of
      adequately preventing the negative effects of these agents are still needed.

PMID- 12001337
TI  - Severe renal hemorrhage caused by pyelonephritis in 7 horses: clinical and
      ultrasonographic evaluation.
AB  - Case records of 7 horses diagnosed with pyelonephritis were reviewed to determine
      common features that might aid in diagnosis, treatment, and prognosis of this
      disease. All 7 horses had been admitted for evaluation of hematuria. During
      cystoscopy of 5 horses, hemorrhage was observed from one or both ureters. Renal
      biopsy of 1 horse, laboratory analysis of ureteral discharge of 2 horses, and
      renal ultrasonography of all horses indicated that pyelonephritis was the cause
      of hemorrhage. Sonographic renal changes included decreased length, increased
      echogenicity, abnormal outline, loss of corticomedullary distinction,
      pyelectasia, and focal hypoechoic or hyperechoic cortical defects. Renal
      hemorrhage in all horses eventually resolved but recurred in 4 of 5 horses that
      were followed long-term.

PMID- 12001338
TI  - Pneumocystosis associated with canine distemper virus infection in a mink.
AB  - An adult mink from a farm experiencing 100% mortality in affected animals was
      submitted for diagnostic examination. Clinical history included signs of
      respiratory disease, oculonasal discharge, and thickening of footpads. Canine
      distemper virus and Pneumocystis carinii were identified in lung tissue,
      suggesting immunosuppresion and secondary infection due to morbillivirus disease.

PMID- 12001339
TI  - Monitoring injection site lesions in Canadian yearling cattle and cull cows and
      bulls: Spring 1998.
AB  - Injection site lesions were found in 15% top butts, 22% blades, 6% eyes of
      rounds, 0.4% inside rounds, and 8% outside rounds from yearling cattle, estimated
      to cost $7.15/head processed ($15 million annually). In cull cows and bulls,
      lesions were found in 33% outside rounds, estimated to cost $3.56/head processed
      ($2.3 million annually).

PMID- 12001340
TI  - Self-mutilation in rabbits following intramuscular ketamine-xylazine-acepromazine
      injections.
AB  - Following hind leg intramuscular injections of ketamine, xylazine, and
      acepromazine, 4 of 6 rabbits exhibited self-mutilation of the digits. At
      necropsy, the affected sciatic nerve appeared enlarged. Lymphohistiocytic
      perineural inflammation and fibrosis were observed, together with nerve
      degeneration. Neuronal regeneration as the reason for self-mutilation is
      discussed.

PMID- 12001341
TI  - The effect of administering long-acting oxytetracycline and tilmicosin either by
      dart gun or by hand on injection site lesions and drug residues in beef cattle.
AB  - Forty yearling cattle were injected intramuscularly with long-acting
      oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a
      chute 28 days prior to slaughter. The drugs caused injection site lesions and
      antibiotic residues in the neck and thigh that varied by technique, dose, and
      site.

PMID- 12001342
TI  - Intradural spinal arachnoid cyst in a dog.
AB  - An 8-month-old, spayed female dog was presented with signs localizing a
      neurologic lesion between the 3rd thoracic and 3rd lumbar vertebrae. An arachnoid
      cyst was diagnosed by myelography, and a dorsal laminectomy with durotomy was
      performed. The dog continues to do well 1-1/2 year after surgery.

PMID- 12001343
TI  - Lice on horses.

PMID- 12001344
TI  - Veterinary homeopathy: an overview.
AB  - Complementary and alternative therapies, including homeopathy, have a definite
      place in veterinary medicine today. The public is demanding access to a full
      range of conventional and complementary therapies, and the best scenario is to
      have all therapies available, for there is a place and a need for all of them in
      the right situation. In my own practice, I use both alternative and conventional
      therapies, as well as referring patients to specialists, for services such as
      ultrasound and surgery. I believe that the wave of the future is to have
      veterinarians skilled in both complementary and conventional therapies, and to
      have veterinary practitioners who are well enough educated to be able to treat
      the majority of their patients, but who are willing to refer to the appropriate
      "specialist," if the case and the client demand it. Veterinarians are definitely
      becoming more aware of the need for and showing more interest in alternative
      medicine. There are currently several associations in North America for
      veterinarians with an interest in complementary therapies. In 1998, the
      International Veterinary Acupuncture Society (IVAS) boasted 1400 members, and the
      American Holistic Veterinary Medical Association (AHVMA) over 800 (1). There are
      professional courses in veterinary acupuncture, chiropractic, and homeopathy, all
      150-200 hours in length, which provide a good basic understanding of these
      modalities. In most of these modalities, there is also advanced training.
      Conventional teaching institutions are recognizing the need to have veterinarians
      well versed in all aspects of veterinary medicine. Colorado State University has
      offered elective courses for students and on-site courses for practitioners on
      alternative therapies for 3 years (1). These are designed to teach veterinarians
      what the alternative modalities are, whether they are effective, and what it
      takes to become qualified to practise them. The overriding goal in most
      veterinarians' minds is to heal animals and provide the best in care, so that
      animals can live healthy productive lives. Education to keep up with new
      therapies and medications is paramount to this goal. It follows easily that
      knowledge of noninvasive treatments with few or no side effects that have the
      potential to heal animals should be welcomed, and homeopathy, as well as other
      complementary therapies, fits this description.

PMID- 12001345
TI  - Update on therapy of canine epilepsy.

PMID- 12001346
TI  - Relationships between mothers, doctors and nurses during childhood chronic
      illness.

PMID- 12001347
TI  - Thinking the worst: major incidents involving children.

PMID- 12001348
TI  - Consumer groups: shaping education and developing practice.

PMID- 12001349
TI  - Keep taking the tablets? Evidence-based approaches to AD(H)D. Part 1: The
      evidence.

PMID- 12001350
TI  - Child and adolescent mental health services: rhetoric and reality.

PMID- 12001351
TI  - Quality and quantity.

PMID- 12001352
TI  - Assessing dependency in a community hospice service.

PMID- 12001353
TI  - Antipyretics in the paediatric A&E setting: a review.

PMID- 12001354
TI  - Growth and failure to thrive.
AB  - Monitoring of growth in early life is particularly important as growth is elastic
      and sensitive to environmental factors, especially nutrition. Deficits are
      unlikely to be recovered fully in a later period and early growth patterns
      contribute to many diseases of adulthood. Assessment of rate of growth, rather
      than attained size, is possible with today's charts and accurate measurement.
      Growth monitoring is important for recognition of failure to thrive and it is
      valuable as a proxy measure for wellbeing. Many factors can contribute to failure
      to thrive which is best managed using a multidisciplinary approach.

PMID- 12001356
TI  - [How quickly is a child's cancer diagnosed?].

PMID- 12001355
TI  - [Stem cells from the umbilical cord blood].

PMID- 12001357
TI  - [Cardiac massage only is sufficient when giving basic life support].

PMID- 12001358
TI  - [New trends of venous surgery].

PMID- 12001359
TI  - [Clinically significant complement deficiencies].

PMID- 12001360
TI  - [Assessment of the information gathered during basic medical education].

PMID- 12001361
TI  - [Akathisia--a state of agitation caused by drug].

PMID- 12001362
TI  - [Fever and increased serum lactate dehydrogenase level after bone marrow
      transplantation].

PMID- 12001363
TI  - [Dyspnea in a patient with pancreas cancer].

PMID- 12001364
TI  - [On media, depression and medicalisation].

PMID- 12001365
TI  - [Treatments of benign prostatic hypertrophy and their cost-benefit relationship].

PMID- 12001366
TI  - [Interventional magnetic resonance sonography].

PMID- 12001367
TI  - [Proton spinlocking and T1 rho-weighted MR imaging at 1.5 T].
AB  - During spinlocking, the magnetization is aligned along an oscillating field (RF)
      and relaxes with time constant T1 rho, the spin-lattice relaxation time in the
      rotating frame. Using a clinical whole-body MR scanner, methods of spinlocking
      preparation and signal acquisition were combined to evaluate the potential of T1
      rho-weighted MR imaging (T1 rho w-MRI) at B0 = 1.5 T. Examinations of the brain
      of healthy volunteers yielded images with pronounced contrast and T1 rho
      variation of the tissue. However, the contrast resembled that of T2-weighted MRI,
      which is explained by the restricted spinlocking-field strength (BSL < or = 6
      microT) on the tomograph. The result (mono-exponential fit) of serial T1 rho w
      MRI data from examinations of 8 volunteers was on average 105 +/- 4 ms in the
      gray matter and 86 +/- 4 ms in the white matter (for BSL = 3 microT). The values
      are comparable to T2 of both tissues. MRT with spinlocking is less susceptible to
      local magnetic field inhomogeneities than conventional MRI.

PMID- 12001368
TI  - [Practical electron dosimetry. A comparison of different types of ionization
      chambers].
AB  - Since Markus chambers are no longer recommended in the 1997 DIN 6800-2 version
      there are uncertainties as to the use of alternative chamber types for electron
      dosimetry. Therefore, we performed a comparison between different types of
      ionization chambers. In particular, the widespread Farmer and Roos chambers were
      compared with the Markus chamber for polarity effect, chamber-to-chamber
      variation, and deviations of the measured absorbed dose relative to the value
      obtained with the Roos chamber (which is regarded as an ideal Bragg-Gray
      chamber). The perturbation correction factor at 60Co radiation was determined
      experimentally as 1,029 +/- 0.5% (Roos chamber) and 1,018 +/- 0.5% (Markus
      chamber) for the investigated plane-parallel chambers. In addition, we could show
      that the Roos chambers do not have a larger chamber-to-chamber variation than the
      Farmer chambers. Likewise, our results suggest that Farmer chambers could be used
      for electron energies above 6 MeV.

PMID- 12001369
TI  - [Dose distribution of asymmetric fields: comparison of the Helax-TMS with our
      developed 2D-program ASYMM].
AB  - The purpose of this investigation was to compare the commercial 3D-treatment
      planning system Helax TMS to a simple 2D program ASYMM, concerning the
      calculation of dose distributions for asymmetric fields. The dose calculation
      algorithm in Helax-TMS is based on the polyenergetic pencil beam model of
      Ahnesjo. Our own developed 2D treatment planning program ASYMM, based on the
      Thomas and Thomas method for asymmetric open fields, has been extended to
      calculate the dose distributions for open and wedged fields. Using both methods,
      dose distributions for various asymmetric open and wedged fields of a 4-MV Linear
      accelerator were calculated and compared with measured data in water. The
      agreement of the Helax-TMS and the ASYMM with the experiment was good, whereas
      ASYMM showed a better accuracy for larger asymmetric angles. The explanation for
      this result is based on the consideration of beam hardening within the flattening
      filter and edges for different asymmetric settings in ASYMM algorithm. The TMS,
      however, owns the diverse possibilities that the 3D calculation and corresponding
      representation provide and holds better application opportunities in clinical
      routine.

PMID- 12001370
TI  - [Optoacoustic spectroscopy and imaging].
AB  - Optoacoustic methods are based on the thermoelastic effect, according to which a
      short laser pulse is absorbed in a medium and generates an acoustic wave
      following rapid heating and thermal expansion. This study it sought to
      demonstrate how the optical properties and structure of the sample can be
      obtained from acoustic signals that are measured on the surface of the medium.
      This was pursued on the hand by using broadband piezo-electric and optical
      sensors, and on the other hand by means of theoretical simulations. For optically
      one-dimensional media, where the optical properties depend only on one direction
      in space, the measurement of a plane wave in the acoustical near field of the
      sample yielded directly the depth distribution of absorbed energy. In the far
      field, this simple relationship was not valid, due to acoustic diffraction. The
      distribution, however, could be reconstructed mathematically. Far field signals
      could also be used to image the contours of optical structures.

PMID- 12001371
TI  - [Mounting device for constancy tests of linear accelerators according to DIN 6847
      5].
AB  - According to the German Industrial Norm DIN 6847-5 for constancy tests of linear
      accelerators, the measurements of the dose-monitor calibration and of the
      flatness of electron and photon beams for four different gantry angles are
      mandatory. The mounting devices developed in the Clinic for Radiation Therapy in
      Augsburg offer the possibility to perform all necessary constancy tests.

PMID- 12001372
TI  - DGMP guideline for medical physical aspects of intravascular brachytherapy. Part
      I: Guideline.

PMID- 12001373
TI  - [Safety aspects in interventional MRI].
AB  - Because of its high soft-tissue contrast, Magnetic Resonance Imaging (MRI) is
      used increasingly for guidance and control of minimal invasive and neurological
      surgical procedures. Besides common precautions during an MRI investigation,
      special attention has to be paid to the consequences of MR compatibility,
      accuracy of localisation of interventional tools and geometrical distortions. As
      a new application of interventional MR intravascular procedures are developing
      that involve the introduction of guidewires, catheters and miniaturized coils
      with their leads into the blood vessels. Resonant currents and high electric
      fields can develop at the conductor ends, possibly causing burning lesions.

PMID- 12001374
TI  - Case no. 1. Squamous cell carcinoma.

PMID- 12001375
TI  - Case no. 2. Central giant cell lesion.

PMID- 12001376
TI  - Collections depend on solid financial policy.

PMID- 12001377
TI  - Court restricts specialty advertising in Florida.

PMID- 12001378
TI  - Labor laws unveiled.

PMID- 12001380
TI  - NCT announces new birth policy.

PMID- 12001381
TI  - Research into link between genetics and cot deaths.

PMID- 12001382
TI  - HIV risk to asylum seekers' babies.

PMID- 12001383
TI  - Delivering better working lives together.

PMID- 12001384
TI  - News on health and maternity matters.

PMID- 12001385
TI  - The NHS Numbers for Babies (NN4B) project.

PMID- 12001386
TI  - The European Forum of National Nursing and Midwifery Associations.

PMID- 12001387
TI  - Focus on infertility.

PMID- 12001388
TI  - Guidance paper: refocusing the role of the midwife.

PMID- 12001389
TI  - Removing the labels, meeting the needs.

PMID- 12001390
TI  - The best of both worlds: complementary therapies for mothers and babies.

PMID- 12001391
TI  - The NMC: new, modern and effective.

PMID- 12001392
TI  - RCM archives.

PMID- 12001393
TI  - Re: Baby car seats.

PMID- 12001394
TI  - Baby feeding.

PMID- 12001395
TI  - Re: Direct entry.

PMID- 12001396
TI  - Re: pay review.

PMID- 12001397
TI  - International Day of the Midwife 2002.

PMID- 12001398
TI  - "But isn't it depressing?" The vitality of palliative care.
AB  - A common question about palliative care from those unfamiliar with the work is,
      "But isn't it depressing?" This view distances palliative care workers from the
      general public and reflects a deeply held belief that matters associated with
      death and dying are negative. Published definitions fall short of capturing a
      full understanding of the work, making it difficult to communicate the meaning of
      palliative care. This qualitative study examined the experiences of six long-term
      palliative care workers. Palliative care was described as "a way of living" and,
      throughout the descriptions, the concept of "vitality" emerged as the core
      meaning of palliative care. In the current economic environment, where there is
      competition for health care funding, more widespread agreement about the meaning
      of palliative care is important if informed decisions are to be made about
      allocation of resources.

PMID- 12001399
TI  - Antibiotic use in the last week of life in three different palliative care
      settings.
AB  - The purpose of this study was to examine the frequency and types of antibiotics
      prescribed in the last week of life in three different palliative care settings,
      including an acute care hospital, tertiary palliative care unit, and three
      hospice units. A total of 150 consecutive patients were evaluated, 50 in each of
      the three settings. Twenty-nine patients (58%) in the acute hospital setting, 26
      (52%) in the tertiary palliative care unit, and 11(22%) in the hospice settings
      were prescribed antibiotics. In the acute care and tertiary palliative care
      settings, the most frequent route of antibiotic administration was intravenous
      and, in the hospice setting, oral. We conclude that there is marked variability
      in the numbers and types of antibiotics prescribed in these different palliative
      care settings in the last week of life. The high use of intravenous antibiotics
      and the large number of patients who were still receiving antibiotics at the time
      of death indicate the need for further prospective studies.

PMID- 12001400
TI  - Addressing myths about end-of-life care: research into the use of acute care
      hospitals over the last five years of life.
AB  - Despite very little confirming evidence, one of the most pervasive beliefs about
      dying is that terminally ill people receive a great deal of health care in the
      last few days, weeks, or months of life. A secondary analysis of 1992/93 through
      1996/97 Alberta inpatient hospital abstracts data was undertaken to explore and
      describe hospital use over the five years before death by all Albertans who died
      in acute care hospital beds during the 1996/97 year (n = 7,429). There were four
      key findings: (1) hospital use varied, but was most often low, (2) the last
      hospital stay was infrequently resource intensive, (3) age, gender, and illness
      did not distinguish use, and (4) most ultra-high users were rural residents, with
      the majority of care episodes taking place in small, rural hospitals.

PMID- 12001401
TI  - Palliative care and euthanasia: a continuing need to think again.

PMID- 12001402
TI  - End-of-life care for hematological malignancies: the 'technological imperative'
      and palliative care.
AB  - Recent research indicates that hospice/palliative care practices have not yet
      been integrated into the care of patients with hematological malignancies. As
      research in relation to palliative care and hematological malignancies is in its
      infancy, many of the end-of-life care practices with these diagnostic groups are
      based on unexamined ideas. The findings presented in this article, which are
      taken from recent post-doctoral research on hematological malignancies and
      palliative care, make a contribution to documenting information on what is
      happening to patients and their families in this area. In particular, the
      findings provide insights on issues associated with the patient and carer
      awareness that the patient is dying, understanding of prognosis, and the desire
      to die at home. Such insights are placed in the context of descriptions of the
      patients' experience with treatment during the terminal stage.

PMID- 12001403
TI  - What determines the quality of life of terminally ill cancer patients from their
      own perspective?
AB  - BACKGROUND: Although several instruments have been developed to measure the
      quality of life (QOL) of palliative care patients, a rigorous research study has
      not specifically asked patients themselves what is important to their QOL. It is,
      therefore, not clear whether these instruments measure what is most important to
      these patients' QOL. PURPOSE: To understand the primary determinants of the QOL
      of palliative care patients with cancer. METHOD: The study used a qualitative
      paradigm. Participants were interviewed concerning what was important to their
      QOL. A systematic content analysis of the transcripts was carried out by all the
      investigators. RESULTS: Five broad domains were found to be importnat
      determinants of patient QOL: (1) the patient's own state, including physical and
      cognitive functioning, psychological state, and physical condition; (2) quality
      of palliative care; (3) physical environment; (4) relationships; and (5) outlook.
      CONCLUSIONS: Existing instruments cover many of these domains, but no single
      instrument includes all of the relevant content. The McGill Quality of Life
      Questionnaire, which we developed previously, has been revised based on these
      data.

PMID- 12001404
TI  - Addressing spirituality in pediatric hospice and palliative care.
AB  - Hospice and palliative care principles mandate clinicIans to provide "total" care
      to patients and their families. Such care incorporates not only physical,
      emotional, and psychosocial care, but spiritual care as well. Even though
      considerable attention has been directed to spiritual issues for adult patients
      in hospice and palliative care, spirituality in pediatric palliative care has
      been virtually neglected. The need for guidelines to assess spirituality in this
      population was identified as a priority issue by members of a subcommittee of the
      Children's International Project on Children's Palliative/Hospice Services,
      created under the auspices of the National Hospice Organization. Committee
      members, based on their clinical, research, and personal experiences, identified
      several aspects relevant to spirituality in general, and to spirituality in
      pediatric palliative care in particular, and developed guidelines for clinicians
      in pediatric palliative care. The purpose of this paper is to share the results
      of this committee's work and, in particular, to present their guidelines for
      addressing spiritual issues in children and families in pediatric hospice and
      palliative care.

PMID- 12001405
TI  - The challenge of developing a regional palliative care data system: a tale of two
      cities.
AB  - This article reviews the purposes of health care databases and the findings from
      a literature review of the use of patient databases in palliative care. We
      present the history and goals of databases developed in two Canadian settings,
      Hamilton and Halifax. We present data on the strengths, limitations, and
      difficulties encountered in each setting. We review the types of data collected
      and the potential of these databases, and we offer practical recommendations for
      others looking to set up such systems.

PMID- 12001406
TI  - [Religions and autopsy].

PMID- 12001407
TI  - [Development of analgesia from 1800 to 2000].

PMID- 12001408
TI  - [Hip anatomy and imagery].
AB  - Since the advent of new imaging methods (CT, MRI), plain radiographs still play a
      central role in the evaluation of the non-traumatic painful hip. In rheumatologic
      practice, standing antero-posterior views of the pelvis, bilateral antero
      posterior views of the hips and bilateral lateral view of Lequesne should be
      performed. This first radiographic evaluation can be completed by a CT arthrogram
      in the first stage of osteoarthritis or by MRI in synovitis and epiphyseal
      disorders involving the femoral head (osteonecrosis, transient osteoporosis,
      subchondral fracture). The physician must be aware of the performance of each
      imaging in order to use the appropriate radiological exam in each situation.

PMID- 12001409
TI  - [Osteoarthritis of the hip].
AB  - If all the etiological factors are taken into consideration, idiopathic
      coxarthrosis is less prevalent than formerly. Three factors are new or
      reappraised: sport practice (more than 10 years in competition), certain
      occupations (dancer, heavy load worker) and heritability. Three are classical and
      yet present: developmental dysplasias, acquired dysmorphias and traumas. Hip
      osteoarthritis should be followed up with the help of pain intensity measured on
      visual analog scale, algofunctional index and self-assessment of handicap. These
      3 parameters--and not the X-ray image--are the basis of the decision for total
      hip replacement. However, the latter could be foreseen as necessary within the
      next 1-4 years when a rapid joint space narrowing is observed (about 5-7% of
      cases).

PMID- 12001410
TI  - [Synovial diseases of the hip].
AB  - Synovial diseases of the hip are often overlooked because they are far less
      frequent that osteoarthritis and because this joint is deep and so difficult to
      examine. The more important cause is septic arthritis; it requires an
      hospitalization in emergency. Synovial tissue may also be at the beginning of the
      spondylarthropathy or, more rarely, of rheumatoid arthritis. In acute forms,
      diagnosis must be done before any radiological destructive changes. Aspiration of
      the hip and synovial biopsy are necessary for the diagnosis. In subacute or
      chronic forms, computed tomography and/or magnetic resonance imaging are useful
      tools to suspect the diagnosis and to guide a biopsy.

PMID- 12001411
TI  - [Osteonecrosis of the femoral head].
AB  - The femoral head is the main location of avascular osteonecrosis. The lesion
      remains asymptomatic for several months or years before causing non specific hip
      pain. Risk factors have been identified, mainly femoral neck fractures,
      corticosteroid therapy and related conditions (lupus erythematosus, organ
      transplantations), alcohol abuse, dyslipidemia, sickle cell disease, HIV
      infection, caisson workers, Gaucher's disease, male sex. When typical
      radiological signs are lacking, MRI is the best investigation. Progression toward
      hip joint damage highly depends on the necrotic volume assessed at MRI. The
      combination of plain radiographs which help staging the severity of
      osteonecrosis, and MRI which indicates the prognosis of the lesion, determines
      the therapeutic options: symptomatic pain relief therapies or surgical treatment
      (core decompression, osteotomy or total hip replacement).

PMID- 12001412
TI  - [Bone diseases of the hip].
AB  - Hip pain is likely to be due to a local or regional bone disease when the hip
      joint is painless and of normal mobility by physical examination. Targeting the
      right diagnosis is easy in a patient affected by bone disease (osteoporosis,
      Paget's disease) or when the background of the patient is suggestive (malignancy,
      pregnancy). However it could be more tricky in most cases: transient osteoporosis
      of the hip, bone fissures, Paget's coxopathy, and tumoral cell osteolysis of
      bones surrounding the hip are the main causes, in addition to femoral head
      osteonecrosis, which is detailed in another chapter.

PMID- 12001413
TI  - [Periarticular pathology of the hip].
AB  - The hip region is the seat of a rich and common periarticular pathology, with a
      variable involvement, depending of the location, and needs better knowledge.
      Anyway the clinical examination takes the major place in the diagnostic.
      Trochanteric bursitis and tendinitis are the more common clinical syndrome in
      that regional pathology. Local injections of corticosteroid are still the mean
      modality of the conservative treatment but are not sufficient to avoid recurrence
      or chronicity which may lead to tendon tears. A better knowledge of the
      physiopathology will lead to a better and early recovery. Apatite calcifications
      are not rare around the hip. Great trochanter is the first location, but the
      femoral insertion of the gluteus maximus and vastus lateralis on the linea
      aspera, the lateral side of the acetabulum and the ischial tuberosity are worth
      known. Iliopsoas bursitis, which has some analogy with the popliteal cyst, is
      often underrecognized, like ischial bursitis and tendinopathy.

PMID- 12001414
TI  - [Acquired pathology of the hip in children].
AB  - Hip pathology is a frequent motive for consultation in the field of paediatrics.
      The clinical examination and the radio-imagery both play a central role in the
      diagnostic process. If acute benign synovitis is the principal cause in the
      child, it remains a diagnosis of exclusion and must not in any case lead to a
      missed diagnosis of septic arthritis. Other diagnoses should be evoked according
      to the age of the child: epiphysiolysis, true surgical emergency, primary
      osteochondritis of the hip, early inflammatory polyarthritidies.

PMID- 12001416
TI  - [Formation of evidence-based medicine and investigation (classification)].

PMID- 12001415
TI  - [Hip replacement].
AB  - Total hip replacement is widely in use all over the world. It is an extremely
      beneficial procedure. But some requirements must be fulfilled: an excellent
      indication, a good technique and a special choice of the material in use. For
      elderly patients less demanding, regular metal on polyethylene cemented implants
      are still in use. For younger patients, more sophisticated materials like ceramic
      on ceramic, or metal on metal seem to be more appropriate. The way the prosthesis
      is stabilized, using or not cement, is also of marked importance. Many other
      details are relevant: the approach, the surgical technique, the way the patients
      are followed, the survivorship analysis which can predict partially the outcome
      in the future for a given prosthesis.

PMID- 12001417
TI  - [Ulceration or erosion of the oral and (or) genital mucosa].

PMID- 12001418
TI  - [Chronic obstructive pulmonary disease].

PMID- 12001419
TI  - [Acute pancreatitis].

PMID- 12001420
TI  - [Challenges of genetic diseases. About a genetic disease: cystic fibrosis].

PMID- 12001421
TI  - [Adrenal insufficiency].

PMID- 12001422
TI  - [Myocardial revascularization versus percutaneous transluminal coronary
      angioplasty in the treatment of ischemic cardiopathy].
AB  - BACKGROUND AND OBJECTIVE: Ischemic heart disease affects a high number of
      patients, and may be treated by surgery or coronary angioplasty. The objective of
      this study is to compare the middle term results of both procedures. MATERIAL AND
      METHODS: Between January and March of 1999, 59 patients with a mean age of 65
      years old ranging 46 to 79, were treated with myocardial revascularization (group
      I) and 57 patients with a mean age of 59 years old ranging 33 to 88 were
      submitted to coronary angioplasty (group II). It was evaluated and compared risk
      factors, morbidity, mortality, evolution in two years after the procedures,
      presence of symptoms, freedom of events. RESULTS: In group I a higher number of
      diabetic patients was found. The 89.8% of patients was asymptomatic two years
      after the procedure in group I against 52.6% in group II (p = 0.03). One patient
      in group I presented angina six months after the procedure and 27 patients in
      group II (47.3%), presented angina between the first seven months after the
      procedure (p = 0.034). Morbidity affects in special to diabetic patients and was
      higher in group I. Mortality was similar in both groups: 6.7% for group I and 6%
      in group II. The length of stay in hospital was lower in group II (p = 0.03).
      CONCLUSION: In a middle time, coronary artery bypass grafting offers better
      results related to freedom of angina and better quality of life.

PMID- 12001423
TI  - [Usefulness of scintigraphy images with 111In-CYT-103 in the diagnosis of colonic
      and rectal recurrence].
AB  - OBJECTIVE: To determine the effectiveness of radioimmunoscintigraphy (RIC) with
      111In-CYT-103 in detecting the extension of malignant disease in patients
      surgically treated for colorectal adenocarcinoma under suspicion of recurrence in
      comparison to CT scan (computed tomography) and exploratory laparotomy. DESIGN:
      Prospective and observational study. MATERIAL AND METHODS: A total of 26 patients
      under suspicion of recurrence, with a total of 31 lesions. All the patients had
      performed the following studies with GT, RIC with 111In-CYT-103, exploratory
      laparotomy and histopathology. RESULTS: A sensitivity of 96.8%, and specificity
      of 77.8%, and accuracy of 92% were found for the RIC. CT scan had a sensitivity,
      specificity and accuracy of 71.5%, 88.8%, and 75.7%, respectively in extrahepatic
      lesions. When both methods are combined, results shows an increment in
      sensitivity. Hepatic lesions were present in 50% of the patients; a sensitivity
      of 85%, a specificity of 92%, and accuracy of 89% for RIC and sensitivity,
      specificity and accuracy of 92% for the CT. CONCLUSION: The results of clinical
      studies with 111In-CYT-103 in detecting the occurrence of colorectal carcinoma
      provided additional information, making this method a valuable complementary test
      that contributes to patient management.

PMID- 12001424
TI  - [Training experience in climacteric and menopause among physicians of the IMSS].
AB  - OBJECTIVE: To analyze the level of knowledge concerning climateric and menopause
      among family physicians and gynecologists and obstetricians of the Instituto
      Mexicano del Seguro Social (IMSS), after a training process in institutional
      technical guidelines and in educational content for population. We also analyze
      possible changes in frequency of medical attention for climateric and menopause
      in the first level of medical care. MATERIAL AND METHODS: Prospective and
      descriptive study on 1) results of the knowledge evaluation by means of 23
      questions with multiple answers, and 2) analysis of rates of medical care for
      menopausal and perimenopausal disturbances (N95 code, X Revision, IDC) from 1995
      to 2000. RESULTS: The percentage of correct answers prior to training was 62.2
      for family physicians and 65.9 for gynecologists and obstetricians; after
      training, 79.3 and 81.4, respectively. Both groups had on increase in knowledge
      levels (p < 0.001) but there were no differences among them. An increase was
      registered in medical care rates for menopausal and perimenopausal disturbances
      in the group from 45 to 64 years of age in the period from 1995 to 2000.
      CONCLUSIONS: All physicians had on increase in knowledge on climateric and
      menopause issues but without differences among them, probably because the care of
      this health problem is referred to specialized services and as well as to more
      attention on other more frequent problems in women's health. In addition, we did
      not find changes yet in the rates of medical attentions attributable to training
      and information to population.

PMID- 12001425
TI  - [Family violence. A hereditary or a learned problem?].

PMID- 12001426
TI  - [Alleles of the major histocompatibility system associated with susceptibility to
      the development of Takayasu's arteritis].
AB  - OBJECTIVE: Since 1972, the relationship between HLA alleles and the
      susceptibility for Takayasu arteritis (TA) has been studied on different
      populations. Hence the results up to date are heterogeneous, the objective of the
      present review is to analyze the relationship between the presence of HLA alleles
      and the susceptibility for the development of TA considering the ethnic origin of
      the studied populations. MATERIAL AND METHODS: We carried out a bibliographic
      review from clinical articles of case and controls studies on different
      populations on which the relationship between HLA alleles and the susceptibility
      for TA was studied, published since 1972 until February 2000. RESULTS: We
      reviewed articles of studies on Asian, Arab, North-American and Mexican Mestizo
      populations. On Asian populations TA was associated with HLA-A31, -B52, -B39, -B5
      and -DR2, on Arabs with HLA-A2, -A9, -B35 and -DR7, on North-Americans with HLA
      DR4 and on Mexican Mestizo with HLA-B5, -B52 and -DR6. On the other hand, recent
      reports establish that several HLA-B alleles (HLA-B52 and HLA-B39) associated
      with the disease share some residues important on the antigen presentation.
      CONCLUSIONS: Hence the heterogeneity of the results obtained up to date, it
      stands out the increase on HLA-B52 and HLA-DR4 reported on ethnically different
      populations. More recent data point the possible participation of an epitope
      located on the peptide-binding site of the HLA-B molecule (positions 63 and 67)
      that seems to be shared by several alleles associated with the disease. These
      residues might be participating on the presentation of an unknown antigen that
      would unchain the disease on the genetically susceptible individuals group.

PMID- 12001427
TI  - [A 20-year-old man with dyspnea, eosinophilia, and subcutaneous nodules].

PMID- 12001428
TI  - [Traumatic subarachnoid-pleural fistula secondary to non-penetrating thoracic
      gunshot wound].
AB  - INTRODUCTION: Traumatic subarachnoid-pleural fistula (TSPF) is very unusual and
      is due to the anomalous communication between the pleural and subarachnoid space.
      We report a TSPF by Bullet wound that was not penetrating to the thoracic cavity.
      CLINICAL CASE: Masculine of 34 years-old that receives wounded by bullet in the
      posterior face of thorax. A pleural effusion was identified and medullar wound
      with fracture of the fifth thoracic vertebra. The effusion is persist and also
      added headache appear. TSPF was diagnosed for myelography. The patient die before
      carrying out the surgical treatment. A massive tromboemboly of lug was the cause.
      The autopsy confirmed the diagnosis. DISCUSSION: The TSPF should be suspected by
      the association of medullar lesion with a persistent pleural effusion. The
      diagnosis should be confirmed by radiology. The treatment can be medical or
      surgical.

PMID- 12001429
TI  - [Precursors of pediatrics in Mexico. Dolores Sanz Pediatric Hospital].

PMID- 12001430
TI  - [Morphea associated with orbital sclerosis].

PMID- 12001431
TI  - [Genes and asthma].

PMID- 12001432
TI  - [Pharmacoeconomic analysis of the short scheme praziquantel in the treatment of
      neurocysticercosis].
AB  - The effectiveness of the treatment of neurocysticercosis with praziquantel has
      been assessed in several clinical trials in the last 20 years. Most studies
      employed a dose of 50 mg/kg/day, three times at day during 2 weeks. Recently, a
      novel and brief dosage scheme of praziquantel has been described. This scheme
      employs three doses of 25 mg/kg, and all are administered separately on the same
      day, with interval of 2 hours. This scheme has a direct impact on direct costs
      (cost of drugs), with a 90% reduction of the traditional scheme. In addition to a
      favorable impact on direct costs, the impact on indirect costs is important: with
      the short-scheme, hospitalization in unnecessary, and costs of hospital visits
      for patient and family is avoided, with subsequent improvement of emotional
      status and family environment.

PMID- 12001433
TI  - [Preimplantation genetic diagnosis (PGD) and sex selection].

PMID- 12001434
TI  - [Various anthropologic features of the physician-patient encounter with pulmonary
      tuberculosis in Western Mexico].
AB  - The present work has as its purpose a description of the information exchanged
      during doctor-patient encounters immediately following diagnosis of pulmonary
      tuberculosis. To accomplish this nine such encounters were audiotape at two
      public health clinics in Guadalajara, Mexico. Communication of information and
      affect was evaluated by adapting the Roter interactional process analysis.
      Results show that the physician instructed the patient to behave in ways to
      prevent disease transmission while assuring patient recovery. Virtually lacking
      from these recordings is evidence of physician concern with the struggle patients
      experience to incorporate this regimen of directly observed therapy in to their
      daily lives. Because these sessions are managed by clinicians to encourage a
      unidirectional flow of information from physician to patient, the former fail to
      attain either patient cultural understanding of his/her disease process or
      comprehensive understanding of how he is affected she by the illness.

PMID- 12001435
TI  - [The elite and the political transition in Mexico].

PMID- 12001436
TI  - Rural practice.

PMID- 12001437
TI  - State-of-the-art breast care: Multidisciplinary Breast Conference.
AB  - State-of-the-art breast care has become highly sophisticated over the past 20
      years. Dialogue among participating breast imagers, pathologists, surgeons,
      medical oncologists, radiation oncologists, plastic and reconstructive surgeons,
      as well as genetic counselors, can only complement and enhance the care of the
      breast cancer patient. In an ongoing effort to offer an open forum to such breast
      care experts, the Multidisciplinary Breast Conference was launched in December
      2000.

PMID- 12001438
TI  - Buzzwords in medical education: what they are, what they mean, and what we are
      doing about them at the University of Kentucky College of Medicine.
AB  - This article defines common buzzwords used to describe innovations in teaching
      medical students. As background for outlining the innovative educational programs
      in place at the University of Kentucky College of Medicine, the dual, or bimodal,
      missions of the College and their historical antecedents are presented.
      Definitions of important educational outcomes, or standards of achievement
      expected from University of Kentucky College of Medicine graduates, including
      professionalism, active learning, evidence-based medicine, and cultural diversity
      are given. In addition, their relevance to the development of medical
      professionals is outlined, and examples of where and how these standards are
      introduced in the Kentucky Medical Curriculum are presented. Similarly,
      definitions and examples of educational methods or pedagogies used to teach our
      medical students are discussed including the use of problem-based learning,
      computer-based instruction, standardized patients, and performance-based
      assessment.

PMID- 12001439
TI  - Rounding up the usual suspects.

PMID- 12001440
TI  - [Should estrogen replacement therapy be questioned?].

PMID- 12001441
TI  - [Balloon dilatation therapy in acute myocardial infarction].

PMID- 12001442
TI  - [Ethics is wisdom and caring].

PMID- 12001443
TI  - [Estrogen and sleep].

PMID- 12001444
TI  - [Geographical differences in mortality and their history].

PMID- 12001445
TI  - [Diagnosis and treatment of autonomic dysreflexia].

PMID- 12001446
TI  - [Dermatological side-effects of inhaled corticosteroids].

PMID- 12001447
TI  - [On aphorisms].

PMID- 12001448
TI  - [A transient weakening of vision in a young woman].

PMID- 12001449
TI  - [Genome research in year 2000].

PMID- 12001450
TI  - [Where is the genome project leading to?].

PMID- 12001451
TI  - [Mice, yeasts and flies--what do genes of the model organisms tell about life and
      its evolution].

PMID- 12001452
TI  - [Genetics of asthma and atopy--how to interpret results from the candidate gene
      studies?].

PMID- 12001453
TI  - [Genes and hypertension].

PMID- 12001454
TI  - [Genetic databases and their use].

PMID- 12001455
TI  - [Will genes become an engine to the industry?].

PMID- 12001456
TI  - [Osteoporosis].

PMID- 12001457
TI  - [How useful is carotid endarterectomy?].

PMID- 12001458
TI  - [Elderly persons from institutions to assisted living--home care services not in
      order].

PMID- 12001459
TI  - [Chronic arthritis in Finland].

PMID- 12001460
TI  - [Neuropsychology in research and therapy of schizophrenia].

PMID- 12001461
TI  - [Midwinter rhabdomyolysis].

PMID- 12001462
TI  - [Fears during pregnancy].

PMID- 12001463
TI  - [Stress during pregnancy and temperament of the child].

PMID- 12001464
TI  - [Listening to a patient who goes through an abortion].

PMID- 12001465
TI  - [Father and pregnancy].

PMID- 12001466
TI  - [Fears of childbirth and their treatment].

PMID- 12001467
TI  - [Postpartum depression].

PMID- 12001468
TI  - [Postpartum psychosis].

PMID- 12001469
TI  - [Stillbirth].

PMID- 12001470
TI  - [Pregnancy of a drug-abuser].

PMID- 12001471
TI  - [Can intelligence be increased with drugs?].

PMID- 12001472
TI  - [Program for the prevention and therapy of diabetes].

PMID- 12001473
TI  - [HER-2/neu oncogene in the selection of treatment for breast cancer and as a
      target of immunotherapy].

PMID- 12001474
TI  - [Corticosteroids in the treatment of multiple sclerosis and optic neuritis].

PMID- 12001475
TI  - [The first diagnosis of Farber's disease in Finland].

PMID- 12001476
TI  - [Treatment of warts].

PMID- 12001477
TI  - [Headache, nausea and fainting attacks].

PMID- 12001478
TI  - [Treatment of poisonings needs some ventilation].

PMID- 12001479
TI  - [Good treatment after attempted suicide reduces fatal poisonings].

PMID- 12001480
TI  - [On the body's defense mechanisms against poisons].

PMID- 12001481
TI  - [Gastric lavage and emesis from the rule to an exception].

PMID- 12001482
TI  - [Toxic syndromes that accompany poisonings].

PMID- 12001483
TI  - [Arrhythmias in acute poisonings].

PMID- 12001484
TI  - [Principles of diagnostics and first line treatment of poisonings].

PMID- 12001485
TI  - [Emergency treatment of drug and narcotic poisoning].

PMID- 12001486
TI  - [Plant and mushroom poisonings--fiction and fact].

PMID- 12001487
TI  - [Alcohol poisonings].

PMID- 12001488
TI  - Good news not so good for healthcare lobbyists. As pols struggle with 'budget
      neutrality,' groups say hospitals, home health doing OK.

PMID- 12001489
TI  - Bitter grapes. OB/GYN group told to disband in price-fixing case.

PMID- 12001490
TI  - New PPS gets A-OK. Long-term providers give thumbs-up to CMS' new reimbursement
      method.

PMID- 12001491
TI  - Into the mainstream. UPMC in venture merging cancer care, telemedicine.

PMID- 12001492
TI  - Defense! Defense! GPOs, under fire, get A in own study.

PMID- 12001493
TI  - Doc sanctions rise slightly.

PMID- 12001494
TI  - Is AHA's plate too full? Scattershot lobbying blurs focus in congress.

PMID- 12001495
TI  - No one's safe from 'Enronitis'. A plague of corporate failures affects the
      healthcare industry, too.

PMID- 12001496
TI  - Loosening their grip. As HMOs' popularity continues to erode, more plans turn to
      less-restrictive rules. But with costs rising, what's next?

PMID- 12001497
TI  - By the numbers. 25 largest national managed-care organizations. Ranked by total
      HMO enrollment (as of Jan. 1, 2001).

PMID- 12001498
TI  - Answers, at last. After three years of waiting, the IRS' merger financing
      guidelines provide a solution for the not-for-profit healthcare industry.
AB  - The long wait is finally over for the not-for-profit hospital industry. After
      three years of intense scrutiny, the Internal Revenue Service has proposed rules
      for consolidating tax-exempt debt. For not-for-profits, this move means that
      merger refinancing can continue for many deals left on hold. IRS lawyer Bruce
      Serchuk (left) helped draft the new rules, which also provide a clear path to
      closure for mergers completed with acquisition financing.

PMID- 12001499
TI  - An ethicist's commentary on the elderly couple rescuing animals.

PMID- 12001500
TI  - Vaccination against foot-and-mouth disease: the implications for Canada.
AB  - Vaccination of susceptible animals against foot-and-mouth disease (FMD) is a well
      established strategy for helping to combat the disease. Traditionally, FMD
      vaccine has been used to control a disease incursion in countries where the
      disease has been endemic rather than in countries considered free of the disease.
      In 2001, the use of vaccine was considered but not implemented in the United
      Kingdom (1), whereas vaccine was used to help to control FMD in The Netherlands
      (2,3). Canadian contingency plans provide for the use of vaccine; Canada is a
      member of the North American Foot-and-Mouth Disease Vaccine Bank, which could
      supply vaccine if needed. This article explains why Canada might use FMD vaccine
      to combat an outbreak and the factors that are relevant to the disposal of
      vaccinated animals and their products. It concludes that vaccination is an
      important mechanism in Canada's preparedness for an outbreak of FMD and that
      products from vaccinated animals are safe for human consumption.

PMID- 12001501
TI  - A comparison of prophylactic efficacy of tilmicosin and a new formulation of
      oxytetracycline in feedlot calves.
AB  - Two replicated-pen field studies were performed under commercial feedlot
      conditions in western Canada to compare the administration of long-acting
      oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to
      feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty
      nine, recently weaned, auction market derived, crossbred beef steer and bull
      calves were randomly allocated upon arrival at the feedlot to one of 2
      experimental groups as follows: oxytetracycline, which received intramuscular
      long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or
      tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a
      rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1
      and in the combined analysis, the initial undifferentiated fever (UF) treatment
      rate was significantly (P < 0.05) higher in the oxytetracycline group as compared
      with the tilmicosin group. There were no significant (P > or = 0.05) differences
      in first UF relapse, second UF relapse, third UF relapse, overall chronicity,
      overall rail, overall mortality, bovine respiratory disease (BRD) mortality,
      hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates
      between the experimental groups in either study or in the combined analysis. In
      addition, there were no significant (P > or = 0.05) differences in initial
      weight, final weight, weight gain, days on feed, daily dry matter intake, average
      daily gain, or the dry matter intake to gain ratio between the experimental
      groups in either study or in the combined analyses. In the economic analysis,
      there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline
      group, due to a lower prophylactic cost, even though the UF therapeutic cost was
      higher.

PMID- 12001502
TI  - Seroprevalence of Coxiella burnetii in selected populations of domestic ruminants
      in Newfoundland.
AB  - The seroprevalence of Coxiella burnetii among cattle, sheep, and goats in
      Newfoundland was determined by microimmunofluorescence. Seropositivity to phase
      II antigen increased in sheep from 3.1% in 1997 to 23.5% in 1999-2000 (P <
      0.001). Cows (24%) had antibodies to phase I antigen; goats (15.6%) had
      antibodies to phase II antigen. Seroprevalence of C. burnetii is increasing among
      sheep.

PMID- 12001503
TI  - Segmental aplasia of the caudal vena cava in a dog.
AB  - Ultrasonography, angiography, magnetic resonance imaging, and exploratory
      laparotomy of a 2-year-old wheaten terrier with lethargy, exercise intolerance,
      and ascites revealed segmental aplasia of the caudal vena cava with azygos
      continuation, complicated by thrombus formation. Surgeries were performed on the
      blind-ended vessel to remove thrombi, enhancing shunting of blood through the
      azygos vein.

PMID- 12001504
TI  - Disseminated Mycobacterium avium infection in a cat.
AB  - A domestic shorthair cat was presented for lethargy and ataxia. Clinical findings
      included an abdominal mass, lumbosacral pain, ataxia. Aspirates from the liver
      and lymph nodes revealed intracellular, negative-staining rods. Treatment for
      presumptive mycobacterium infection was unsuccessful and the cat was euthanized.
      Disseminated Mycobacterium avium was confirmed on culture.

PMID- 12001505
TI  - Acute penitrem A and roquefortine poisoning in a dog.
AB  - Penitrem A and roquefortine poisonings were diagnosed in a Laborador retriever
      following garbage consumption. Clinical signs of mycotoxicosis included polypnea,
      tachycardia, and ataxia that quickly progressed to lateral recumbency and
      seizures. Removal of the mycotoxins from the stomach soon after ingestion allowed
      the dog to recover within 72-96 hours.

PMID- 12001506
TI  - Hematuria and a complex congenital heart defect in a newborn foal.
AB  - A 16-hour-old foal was referred for evaluation of hematuria. A pansystolic heart
      murmur and left thoracic thrill were detected; laboratory diagnostics and
      ultrasonography identified a complex congenital heart defect. The diagnosis was
      confirmed at postmortem.

PMID- 12001508
TI  - South Carolina nurse ethics column.

PMID- 12001507
TI  - Malocclusions in guinea pigs, chinchillas and rabbits.
AB  - The types of malocclusions encountered in rodents and lagomorphs are classified.
      Diagnosis, treatment, and prognosis are reviewed. Some malocclusions are curable,
      whereas others can only be controlled. The need to perform a complete oral
      examination and to find a cause for the condition is stressed, as it will
      seriously affect the prognosis.

PMID- 12001509
TI  - Next--the doctor shortage.

PMID- 12001510
TI  - Hailing one of health care's priceless resources--nurses commentary.

PMID- 12001511
TI  - Nurses say health and safety concerns play major role in employment decisions.

PMID- 12001512
TI  - Nursing shortage--one solution: technology helps nurses re-enter the workforce.

PMID- 12001513
TI  - Advisory Opinion #42-formulated: January 24, 2002.

PMID- 12001514
TI  - Tragedy in Charleston leaves two dead and one injured.

PMID- 12001515
TI  - "And what has become clear to you since we last met?".

PMID- 12001516
TI  - Nursing Informatics 101. What is nursing informatics?

PMID- 12001517
TI  - Managing soft tissue injuries.

PMID- 12001518
TI  - The National Poisons Information Service.

PMID- 12001521
TI  - Changes in the use of emergency services.

PMID- 12001523
TI  - Paediatric resuscitation: advanced life support.

PMID- 12001524
TI  - Painful lessons.

PMID- 12001525
TI  - Covert pregnancy testing.

PMID- 12001526
TI  - [Vasculitis with associated skin changes and dermatitis with associated
      vasculitis].
AB  - By applying strict diagnostic criteria and a standardized classification (Chapel
      Hill 1994) an attempt has been made to shed some light on the varying and
      sometimes puzzling information concerning the quantity and quality of skin
      lesions with systemic vasculitis or vasculitis associated with certain types of
      dermatitis. It has to be emphasized that associated skin lesions are hereby non
      specific. However, a palpable purpura with a predeliction for the lower
      extremities is considered to be quite typical. The same diagnostic criteria as
      for systemic vasculitis should also be applied to dermatitis with associated
      vasculitis. It also has to be stressed that not all patients with a certain type
      of dermatitis necessarily show a vasculitis. However, if present, an associated
      vasculitis does not always involve all blood vessels, therefore it may not show
      up in each histological section examined. The gold standard of diagnosis of a
      vasculitis is a biopsy with hematoxylin staining and in additional van Gieson
      elastica staining may be helpful. According to actual experience gained since
      their introduction, immunohistochemical and immunological methods play only a
      supportive role.

PMID- 12001527
TI  - [Tumors of the lymphatic vessel of the skin and soft tissue].
AB  - Tumours of lymphatic vessels comprise only a small group in the heterogeneous
      spectrum of vascular neoplasms of skin and soft tissues. However, this
      discrepancy between haemangiomas/angiosarcomas and
      lymphangiomas/lymphangiosarcomas probably represents the present inability to
      reliably differentiate between lymphatic and capillary vascular endothelium.
      Histologically, neoplastic lymphatic vessels tend to be lined by endothelial
      cells with plumper and more prominent, matchstick-like nuclei (in contrast to
      vascular spaces in haemangiomas that are lined by flat or epithelioid endothelial
      cells), often show variations in the thickness of the vessel walls and are not
      completely surrounded by actin-positive (myo)pericytes. Endothelial cells in
      lymphatic neoplasms tend to be negative for CD34 or stain only focally positive
      for this marker and an expression of lymphatic markers as vascular endothelial
      growth factor-C receptor (VEGRF-3), podoplanin and M2A oncofetal antigen has been
      reported most recently. In addition to "traditional" lymphatic neoplasms
      including lymphangioma circumscriptum, cavernous lymphangioma/cystic hygroma,
      benign lymphangioendothelioma, lymphangiomatosis and the rare lymphangiosarcoma,
      histological and immunohistochemical features of a group of vascular neoplasms
      with a hobnail cytomorphology (hobnail haemangioma, retiform
      haemangioendothelioma, papillary intralymphatic angioendothelioma, benign
      lymphangiomatous papule following radiotherapy) suggest that these lesions also
      belong to the spectrum of tumours of lymphatic vessels.

PMID- 12001528
TI  - [The dysplastic nevus. An Ariadne's thread through a conceptual labyrinth].
AB  - The concept of the dysplastic nevus is flawed by inconsistencies regarding the
      clinical presentation, histological features and biological considerations. With
      regard to basic mechanisms of malignancy, dysplastic nevi exhibit neither
      increased proliferation indices nor elevated telomerase activity. These traits
      denote a benign lesion that is highly prevalent among Caucasians. In rare cases,
      the distinction from malignant melanoma may pose problems.

PMID- 12001529
TI  - [IUD-associated pseudoactinomycotic gradiate granules (Spendore-Hoeppli
      phenomenon) in uterine curettage].
AB  - Pseudoactinomycotic radiate granules, also known as the Splendore-Hoeppli
      phenomenon represent a response to organic and in-organic foreign substances and
      can be found at various locations in the body. They are frequently observed in
      uterine curettages, where they can be misinterpreted as actinomycotic sulfur
      granules. Here we report a case with Splendore-Hoeppli phenomenon in an
      intrauterine device (IUD)-associated genital actinomycosis. The morphological
      features of this phenomenon are presented using special staining methods and
      electron microscopy and the literature is reviewed.

PMID- 12001530
TI  - [Deposition of keinoid fibers in gastrointestinal stromal tumors of the small
      intestine. Report of two cases and review of the literature].
AB  - Skeinoid fibers are interstitial collections of a pathological collagen, most
      often seen in gastrointestinal stromal tumors. They were first described in 1991.
      We report two cases of intestinal stromal tumors, one in an exceptionally young
      patient with excessive skeinoid fiber deposition. The microscopic as well as the
      ultrastructural findings of skeinoid fibers are demonstrated and their role is
      discussed considering the newest literature.

PMID- 12001531
TI  - [Epulis in a newborn. histogenetic comparison with a granular cell tumor in
      adults].
AB  - The congenital granular cell tumor is a rare lesion of newborns located on the
      alveolar ridge with a marked predilection for female infants. Histologically
      these tumors are characterized by large eosinophilic granular cells, similar to
      granular cell tumors in adults which are often seen as Abrikossoff tumors.
      Immunohistochemical studies revealed the different histogenesis and evolution of
      both these tumor entities. We report on a female newborn infant with a congenital
      epulis of the left anterior maxillary alveolar ridge. This case demonstrates a
      rare congenital tumor of newborns and reveals the histogenetic differences to
      granular cell tumors in adults.

PMID- 12001532
TI  - [Eccrine spiradenocarcinoma with unusual histiocytic giant cell components. Case
      report and review of the literature of a rare sweat gland tumor].
AB  - We report the case of a spiradenocarcinoma (malignant eccrine spiradenoma), a
      rare variant of a malignant sweat gland tumor, which occurred in the scalp of a
      63-year-old woman. Some years before the current tumor occurred, a tumour of
      unknown histology had been excised from the same localization. The new tumor
      presented with rapid growth and exulceration. Malignant eccrine spiradenoma is
      characterized by the coincidence of a benign and a malignant portion within one
      specimen. We report case example 47 of this entity. The peculiarity of this case
      is the enormous heterogeneity with foci of atypical histiocytes like an atypical
      fibroxanthoma and an extensive foreign body reaction with cholesterol needles as
      in a xanthogranuloma. Static DNA cytophotometric analysis revealed different
      degrees of aneuploidy in the three tumor portions. The follow-up of 23 months is
      without recurrent tumor. A review of the literature is given.

PMID- 12001533
TI  - [Adenocarcinoma of the stomach with heterotopic ossification. Case report and
      discussion of the pathogenesis].
AB  - Heterotopic ossification of gastric adenocarcinomas is very rarely observed in
      humans. In rats such lesions could be induced by ingestion of nitroso compounds.
      We describe the case of a 70-year-old patient with an extended, initially spleen
      infiltrating tubular adenocarcinoma of the stomach with a mucinous component,
      heterotopic ossifications and pronounced regressive alterations after neoadjuvant
      chemotherapy. Various speculations regarding the pathogenesis of heterotopic
      ossifications in gastrointestinal adenocarcinomas are discussed.

PMID- 12001534
TI  - [Inflammatory myofibroblastic tumor of the pancreas with regional lymph node
      involvement].
AB  - Inflammatory myofibroblastic tumors (IMT) can be found in virtually any location
      of the human body. Histologically a mesenchymal aspect predominates and makes
      these mostly benign tumors apt to be erroneously diagnosed as a soft tissue
      sarcoma. Cases showing infiltrative growth and local recurrence further
      complicate the assessment. Localization of an IMT in the pancreas is extremely
      rare. Clinical investigations regularly lead to the putative diagnosis of a
      malignant tumor and only subsequent histological examination can establish the
      correct tumor classification. We present the case of a 62-year-old woman with IMT
      of the pancreas. Evidence of lymph node involvement has not yet been reported in
      this setting.

PMID- 12001535
TI  - [Why controlled studies may lead to misleading and unconfirmed therapeutic
      concepts--a critical view of evidence-based medicine].
AB  - The concept of evidence-based medicine has gathered widespread support during
      recent years. While this concept has clear merits in compiling and qualifying up
      to-date information for clinical decisions, it should be viewed with caution as
      the sole valid knowledge source for clinical decision-making. The limitations of
      such an approach are particularly striking when reviewing two key developments in
      modern cardiology, fibrinolysis and acute percutaneous intervention in acute
      myocardial infarction. In both cases, early studies and meta-analyses showed no
      benefit for these therapeutic interventions over earlier treatment. Only after
      further refinement (mainly in dosage, time window, concomitant heparin therapy
      for fibrinolysis, and the introduction of stents and IIb/IIIa inhibitors for
      acute intervention) did these therapies become universally acknowledged. It is
      therefore crucial to understand that especially for physicians actively
      participating in the development of a clinical field clinical decisions cannot be
      exclusively based on published evidence. Another important problem to consider is
      the time gap between the emergence of new therapies and the publication and
      reception by the medical audience, in particular in rapidly evolving fields as
      cardiology. While it is clear that clinical decision-making must be backed by
      solid knowledge of the published evidence, in particular the specialist involved
      in-depth in the field may use not yet proven therapeutic concepts and measures to
      the patient's advantage.

PMID- 12001536
TI  - [Coronary revascularization: off-pump versus on-pump--a comparison of behavior of
      biochemical cardiac ischemia markers].
AB  - BACKGROUND: Recently, coronary artery bypass grafting (CABG) on the beating heart
      with avoidance of extracorporeal circulation (off-pump CABG technique) has been
      gaining increasing importance in modern cardiac surgery. The object of this
      prospective study was to compare postoperative kinetic and patterns of cardiac
      troponin I (cTnI), T (cTnT), and creatine kinase MB (CKMB) activities after off
      pump CABG versus conventional on-pump CABG. METHODS: We studied 106 patients who
      underwent first-time elective on-pump (group I, n = 69, 56 male, 13 female, mean
      age: 64.3 +/- 9.9 years, mean ejection fraction: 56 +/- 15%) or off-pump (group
      II, n = 37, 24 male, 13 female, mean age: 68.4 +/- 9.1 years, mean ejection
      fraction: 57 +/- 13%) CABG surgery via median sternotomy. CTn I and cTnT levels,
      total creatine kinase (CK) and CK-MB activities in the serum were measured before
      operation, up on arrival at the ICU and 6, 12, 24, 48 and 120 hours later. Serial
      12-lead ECGs were recorded preoperatively and on days 1, 2 and 5. RESULTS: Serum
      concentrations of cardiac troponins in all patients were preoperatively either
      not detectable or in the normal range and significantly increased after surgery.
      In group I, one patient developed a Q wave myocardial infarction, one patient a
      non-Q wave infarction and two patients a new left bundle branch block on the ECG.
      One patient of group II developed a new Q-wave myocardial infarction and another
      patient permanent atrial fibrillation associated with a continuous arrhythmia.
      All patients with a myocardial infarction in the ECG showed significant elevation
      of concentrations or activities of these biochemical markers. The median
      postoperative peak values for cTnI were measured at 24 h in both groups (2.7
      micrograms/l, 95%-CI: [2.2, 3.2] in group I and 1.1 micrograms/l, 95%-CI: [0.5,
      1.3] in group II). CTnT postoperatively presented an earlier median peak of 0.128
      microgram/l at 12 h in group II (95%-CI: [0.041, 0.146]) than in group I at 48 h
      (0.298 microgram/l, 95%-CI: [0.254, 0.335]). CONCLUSIONS: All patients undergoing
      CABG surgery with or without extracorporeal circulation postoperatively showed an
      increase of cardiac troponin levels. After uncomplicated coronary
      revascularization, patients with the off-pump CABG technique continuously
      presented lower serum cardiac troponin concentrations than those with the on-pump
      CABG technique. CTnI showed the same patterns of release in both groups with
      different median postoperative peak values at 24 h. The patterns off cTnT release
      following CABC surgery with or without extracorporal circulation were different:
      CTnT reaches its postoperative peak value in patients with the off-pump CABG
      technique earlier than those with the on-pump CABG technique (12 h
      postoperatively versus 48 h).

PMID- 12001537
TI  - [Does arteriosclerotic calcinosis of vessel walls imitate osteogenesis?
      Pathomorphological studies of arteriosclerotic plaque].
AB  - OBJECTIVE: For it is supposed that calcification of arteriosclerotic plaques
      imitates osteogenesis, it was studied whether the morphology of different stages
      of calcification supports such an assumption. MATERIAL AND METHODS:
      Investigations were performed on one operation specimen of a dissecting aneurysm
      of the aorta and five human autopsy aortas. From different arteriosclerotic
      plaques, paraffin sections without and after EDTA-decalcification were prepared.
      Light microscopic, scanning (SEM) and transmission electron microscopic (TEM)
      investigations as well as X-ray microanalysis were performed. RESULTS: By light
      microscopy, it became obvious that the intensity of calcification of
      arteriosclerotic plaques is not reflected by the conventional H&E stain--the real
      amount of calcium-phosphorus deposits becomes only evident by using a special
      stain, such as the alizarin red S reaction. In the SEM, arteriosclerotic plaques
      with granular calcification were characterized by accumulations of isolated
      calcified globules often reflecting the structure of necrotic cells. TEM
      exhibited even accumulations of calcified bodies corresponding to the shape of
      cells; cell remnants were present in the neighborhood. X-ray microanalysis of the
      granules detected calcium and phosphorus and a relative high content of
      magnesium, reflecting the composition of calcospherites in granular media
      calcification (71). By SEM, solid calcifications exhibited associations of
      calcified bodies resembling those of the isolated granules in early calcification
      but with one stuck onto the other. X-ray microanalysis revealed that these
      deposits are characterized by high amounts of calcium and phosphorus and a minor
      component of magnesium in comparison to the isolated granules. CONCLUSIONS: From
      the investigations it is concluded that calcification of arteriosclerotic plaques
      imitates the process of granular media calcification which is assumed as
      "dystrophic" calcification of fragments of necrotic cells. The hypothesis of a
      "regulated" calcification as it occurs in cartilage or bone cannot be supported
      for the development of the calcified plaques; however, it cannot be excluded that
      proteins that are associated with osteogenesis participate in the transition of
      calcification to ossification in the vessel wall.

PMID- 12001538
TI  - [Pilot study of the effectiveness of combination therapy with reduced dose
      alteplase and the glycoprotein IIb/IIIa antagonist tirofiban in acute myocardial
      infarct].
AB  - In a pilot study with a total of 43 patients (31 males, 12 females) at a mean age
      of 64.2 +/- 12.1 years, the efficacy of a combination of a reduced dosage of
      alteplase (50 mg) and tirofiban with a start infusion of 0.4 microgram/kg/min
      over half an hour and an infusion rate of 0.10 microgram/kg/min over 12 h (PRISM
      PLUS, modified) in four patients and a bolus of 10 micrograms/kg over 3 minutes
      and an infusion rate of 0.15 microgram/kg/min over 24 h (RESTORE, modified) in 39
      patients were tested in acute myocardial infarction with regard to patency of
      infarct vessel and TIMI flow according to coronary angiography after 60 minutes,
      30-day mortality and bleeding complications. The use of tirofiban in the PRISM
      PLUS dosage led to an infarct vessel patency of 25% with TIMI III flow in one
      case. There were no complications in the next 30 days in this group. The use of
      tirofiban in the RESTORE dosage led to an infarct-vessel patency of 87%, a TIMI
      III flow in 79%, a 30-day mortality of 2.6% and a slight PCI-associated bleeding
      complication in one case. The combination of alteplase in a reduced dosage and
      tirofiban with a single bolus and an infusion rate according to the RESTORE study
      with satisfactory efficacy and low complication rate seems to be useful in the
      management of acute myocardial infarction.

PMID- 12001539
TI  - [Total arterial bypass operations with complete sternotomy in the awake patient].
AB  - BACKGROUND: In minimally invasive coronary artery bypass surgery beating heart
      procedures and operations via limited incisions became more popular and are
      routinely performed in many centers. An additional approach to minimize general
      trauma is avoidance of general anesthesia endotracheal intubation. PATIENTS AND
      METHODS: Between March and June 2001, 14 spontaneously breathing patients
      underwent coronary artery bypass grafting on the beating heart without general
      anesthesia. Intra- and postoperative analgesia management was performed using
      continuous epidural infusion of local anesthetics at level Th2-Th3. Single (n =
      8) as well as double (n = 5) and triple (n = 1) bypass grafting was performed
      with the off pump technique. Surgical access to the chest cavity was created via
      partial (n = 8) or complete sternotomy (n = 6). RESULTS: Twelve patients remained
      awake throughout the procedure; 2 patients required secondary intubation due to
      incomplete sensory block and pneumothorax. Operating time was 94 +/- 18 minutes.
      Intermediate care monitoring time amounted to 4.8 +/- 0.6 hours. No surgery
      related complications or myocardial infarction occurred. Postoperative
      angiography reviewed good graft function in all patients. CONCLUSION: Our
      preliminary experience shows that complete surgical revascularization is safe and
      feasible without endotracheal intubation and general anesthesia. Thus,
      invasiveness in cardiac surgery is further reduced with less need for intensive
      care unit monitoring enabling faster mobilization and recovery.

PMID- 12001540
TI  - [Prevalence and significance of coronary collateral circulation in patients with
      acute myocardial infarct].
AB  - Angiograms from consecutive and unselected patients with acute myocardial
      infarction were studied with respect to the prevalence as well as the
      significance of coronary collateral circulation to myocardium distal to the acute
      coronary occlusion. METHODS: Coronary angiograms were obtained from 700
      consecutive and unselected patients with an acute transmural infarction within
      3.7 +/- 3 hours (0.5-12) of symptom onset. No patient had undergone i.v.
      thrombolysis prior to angiography. Complete and acute vessel occlusion was found
      in 626/700 patients (89%). Coronary collaterals were detected and graded using
      Rentrop's classification. The grade of collateral circulation was related to the
      clinical course after 30 days and to the global and regional left ventricular
      wall motion. RESULTS: Collaterals were found in 334 patients (69%); 242 patients
      (38%) had collateral flow grade 2 or 3. Collaterals were demonstrated more
      frequently in women vs men and in patients with multivessel disease. The
      prevalence of collaterals was unrelated to age and the presence of diabetes
      mellitus. Patients who had angiography within 3 hours of symptom onset had
      collaterals detected less frequently than patients who had angiography beyond 6
      hours (66% vs 75%, p < 0.05). No collaterals were found in 17/37 patients (47%)
      in cardiogenic shock and inferior MI but in only 30/164 patients (18%, p < 0.01)
      without shock. Global and regional left ventricular wall motion after 2 weeks was
      unrelated to the degree of coronary collateral circulation during acute
      myocardial infarction. CONCLUSION: Collateral circulation to myocardium distal to
      an acutely occluded coronary artery is detected in 2/3 patients during the acute
      infarct phase. The absence of collaterals is related to the early occurrence of
      cardiogenic shock in patients with inferior MI but not to the presence of
      diabetes mellitus. After direct angioplasty of the infarct vessel, the protective
      effects of coronary collaterals on chronic LV function remain uncertain.

PMID- 12001542
TI  - [Septic endarteritis after angiography].
AB  - Infectious complications after angiography are rare. We treated a 72-year-old man
      who developed staphylococcus aureus endarteritis after angiography resulting in
      delayed rupture of the common iliac artery. Diagnostic problems, type of bacteria
      involved and therapeutic implications are discussed.

PMID- 12001541
TI  - Low molecular weight heparin for prevention of thromboembolic complications in
      cardioversion--rationale and design of the ACE study (Anticoagulation in
      Cardioversion using Enoxaparin).
AB  - The modality and duration of anticoagulation before, during, and after
      cardioversion of atrial fibrillation--either with or without guidance by
      transesophageal echocardiography (TEE)--is still an unresolved issue. Intravenous
      infusion of unfractionated heparin until effective anticoagulation with
      phenprocoumon or warfarin is used as the standard therapy. However, this approach
      may be associated with several days of hospitalization because of the necessity
      for intravenous heparin administration. Moreover, there may be an increased risk
      of bleeding complications or, conversely, episodes of undercoagulation. Low
      molecular weight heparin is an attractive alternative as it not only provide a
      safe and predictable level of anticoagulation with fewer side effects but can
      also be administered safely on an outpatient basis. In addition, no
      anticoagulation monitoring is needed. The ACE study (Anticoagulation in
      Cardioversion using Enoxaparin) is a randomized, prospective, open-label
      multicenter trial comparing the safety and efficacy of subcutaneous enoxaparin
      with intravenous heparin/oral phenprocoumon before and after cardioversion
      (stratified to TEE guidance or no TEE guidance). This article presents the
      rationale, design and status of the ACE study.

PMID- 12001543
TI  - [Micro-coil embolization of a fistula of the circumflex ramus in the coronary
      sinus. Case report, differential therapy and review of the literature].
AB  - A 45 year old male suffered from typical exercise-induced dyspnoea and angina.
      Crohn's disease treated with glucocorticoids was present for 18 years. Coronary
      angiography revealed small left anterior descending and right coronary arteries
      without reference to coronary artery disease, while the main stem and circumflex
      artery were severely dilated due to a fistula (diameter 5.5 mm) into the coronary
      sinus with a left/right shunt amounting to 35%. Haemodynamics, significant risk
      of endocarditis with chronic inflammatory bowel disease and obligatory
      glucocorticoid treatment were indications for fistula closure. As an alternative
      to surgical correction, the coronary fistula was totally occluded by antegrade
      micro-coil embolization. The present report offers a review on differential
      therapeutic considerations and specific treatment options including novel
      interventional modalities for coronary fistulas.

PMID- 12001544
TI  - [Persistent sinusoids of the left chamber wall].
AB  - Angiographic pictures of persistent sinusoids of the left chamber wall are
      presented. The clinical significance of this very rare phenomen is not clear yet.

PMID- 12001545
TI  - [Aortico-left ventricular tunnel: a rare differential diagnosis of congenital
      aortic insufficiency].
AB  - Aortico-left ventricular tunnel (ALVT) is a rare congenital cardiac malformation
      that presents with cardiac failure and clinical findings of severe aortic
      regurgitation in early infancy. The diagnosis should be made with 2-D
      echocardiography by demonstrating an abnormal tunnel-like structure that connects
      the ascending aorta with the left ventricle. Up to 45% of the patients may have
      associated cardiac defects, and the development of this bizarre lesion is still
      unclear. In contrast to congenital aortic regurgitation, ALVT has a better
      prognosis. Early surgical intervention is curative, but non-operated children die
      because of heart failure. Therefore, knowledge of this rare cardiac malformation
      is mandatory if an infant presents with findings of aortic regurgitation.

PMID- 12001546
TI  - [Retrograde type A dissection after endovascular stent grafting of type B
      dissection].
AB  - Acute aortic dissection is a disease with high mortality. Whereas acute
      dissection of the ascending aorta (Standford type A) is treated surgically, acute
      dissection of Stanford type B (descending aorta) is principally treated
      conservatively, but surgically in case of complications. Recently, another
      therapeutical option for the treatment of type B dissection has been developed
      using endovascular stent-grafts. We report on a 64-year-old woman with typical
      signs of acute aortic dissection. Computer tomography and transesophageal
      echocardiography demonstrated Stanford type B dissection. The patient was treated
      with an endovascular stent-graft, because of malperfusion of the right leg and
      chest pain. After successful closure of the entry by the stent, the patient
      developed acute right-sided hemiplegia one day after the intervention due to
      retrograde dissection into the aortic arch and ascending aorta. Upon immediate
      operation, the origin of the initially type B dissection was still sufficiently
      occluded by the endovascular stent-graft; however, there was another entry
      between the innominate artery and the left carotic artery near one proximal end
      of the stent's strut. Using deep hypothermia and selective antegrade cerebral
      perfusion, the ascending aorta and proximal arch were replaced with a 28 mm
      Dacron-Velour tube and the aortic root was remodelled with a tongue-shaped Dacron
      graft preserving the valve cusps according to a modified Yacoub procedure. After
      the operation, neurological symptoms diminished and the patient could walk on the
      ward on day eleven. This case demonstrates retrograde type A dissection as a
      complication after interventional treatment of type B dissection using an
      endovascular stent-graft. The reason for this delayed complication is
      speculative. Aortic wall damage during stent inserting could be a possible cause.
      It is also likely that the patient initially had type B dissection with
      retrograde dissection of the distal part of the aortic arch. Therefore, one of
      the straight struts of the proximal end of the stent may have caused additional
      damage to the vulnerable dissected aortic wall in the arch, leading to retrograde
      type A dissection. Careful patient selection, detailed diagnosis of the aortic
      arch, improved stent designs and materials, especially regarding the stent's ends
      and careful insertion of the stent into the aortic arch, could contribute to
      prevention of the described problems.

PMID- 12001547
TI  - ["A profile one should have...". A contribution at carnival time].

PMID- 12001548
TI  - An experimental study on mandibular expansion: increases in arch width and
      perimeter.
AB  - The purpose of this study was to estimate the increase in arch perimeter
      associated with mandibular lateral expansion. The mandibular expansion was
      simulated using a three-dimensional (3D) finite element method (FEM) and a
      computer graphics technique (3D simulation). The centre of rotation of molars
      during movement accompanied by lateral expansion was calculated using 3D FEM. The
      geometry of the model was determined using the mandibular bone of an East Indian
      skeletal specimen and 1 mm computer tomogram (CT) slices. The 3D set-up
      simulation was then conducted using 3D computer graphics instead of performing a
      manual set-up. Rotational movement was induced in the buccal segment, from the
      first premolar to second molar, in the 3D set-up model around the location of the
      centre of rotation (4.5 mm below the root apex of the first molar) derived from
      the FEM. According to 3D simulation, the model showed an opening space of 1.43 mm
      between the canine and first premolar, and thus a change in arch perimeter of
      2.86 mm. The tip of the mesio-lingual cusp of the first molar moved 3.88 mm
      laterally, resulting in a change in inter-molar width of 7.76 mm. These values
      mean that a 1 mm increase in arch width resulted in an increase in arch perimeter
      of 0.37 mm. This result would be of value clinically for prediction of the
      effects of mandibular expansion.

PMID- 12001549
TI  - Tooth dimensions in hypodontia patients, their unaffected relatives and a control
      group measured by a new image analysis system.
AB  - Tooth dimensions were compared between index patients with severe hypodontia (six
      or more congenitally missing teeth), their relatives with a full complement of
      teeth, and a control group. The groups consisted of 12 index cases (seven females
      and five males), 21 relatives without hypodontia (13 females and eight males),
      and a control group of 10 males and 10 females with complete dentitions, and no
      family history of hypodontia. All formed teeth were imaged buccally and
      occlusally from study models, with a digital camera linked to a computer. The
      images were acquired and measured using Adobe Photoshop and Image Pro Plus,
      respectively. Mesiodistal, buccolingual, or occlusogingival area and perimeter
      measurements were determined from each image. In the index hypodontia group tooth
      dimensions were significantly smaller (P < 0.001, Bonferroni corrected level) for
      maxillary and mandibular canines, and first premolars for all dimensions from the
      buccal view, and for maxillary and mandibular canines and first premolars,
      maxillary central incisors, maxillary first molars, mandibular lateral incisors,
      and mandibular second premolars for all dimensions from the occlusal view. In the
      relatives without hypodontia compared with the control group, mesiodistal
      dimensions from the buccal view were significantly smaller (P < 0.001) for the
      central incisors and maxillary first and second premolars, and for the maxillary
      and mandibular first premolars for all dimensions from the occlusal view. There
      was a trend for the tooth dimensions of all teeth in the index group to be
      smaller compared with the control group. The tooth dimensions of the relatives
      without hypodontia also tended to be smaller than the control group, but were
      larger than those of the index cases.

PMID- 12001550
TI  - Thin-plate spline analysis of the short- and long-term effects of rapid maxillary
      expansion.
AB  - The aim of this study was to investigate the short- and long-term effects induced
      by rapid maxillary expansion (RME) on the shape of the maxillary and
      circummaxillary structures by means of thin-plate spline (TPS) analysis. The
      sample consisted of 42 patients who were compared with a control sample of 20
      subjects. The treated subjects underwent Haas-type RME, followed by fixed
      appliance therapy. Postero-anterior (PA) cephalograms were analysed for each
      treated subject at T1 (pre-treatment), T2 (immediate post-expansion), and T3
      (long-term observation), and were available at T1 and T3 for the control group
      (CG). The mean age at T1 was 11 years and 10 months for both groups. The mean
      chronological ages at T3 were 20 years, 6 months for the treated group (TG) and
      17 years, 8 months for the control group. The study focused on shape changes in
      the maxillary, nasal, zygomatic, and orbital regions. TPS analysis revealed
      significant shape changes in the TG. They consisted of an upward and lateral
      displacement of the two halves of the naso-maxillary complex as a result of
      active expansion in the short-term, and normalization of maxillary shape in the
      transverse dimension in the long-term (the initial transverse deficiency of the
      maxilla in the treated group was eliminated by RME therapy both in the short- and
      long-term). At the end of the observation period, the nasal cavities were larger
      when compared with both their pre-expansion configuration and the final
      configuration in the controls. RME with the Haas appliance appears to be an
      efficient therapeutic means to induce permanent favourable changes in the shape
      of the naso-maxillary complex.

PMID- 12001551
TI  - Ultrastructure of the human intra-articular disc of the temporomandibular joint.
AB  - The ultrastructural appearance of the human intra-articular disc (IAD) was
      investigated in three discs that had been surgically removed due to disease from
      three female patients aged 47, 50, and 54 years of age. Regions of the IAD were
      selected from central areas that appeared to be least affected by disease.
      Sections were fixed in 2.5 per cent glutaraldehyde in 0.1 M phosphate buffer, pH
      7.3 immediately after surgery. The regions examined showed no obvious signs of
      inflammation. The cells showed moderate amounts of the intracellular organelles
      associated with protein synthesis and secretion, and possessed considerable
      amounts of microfilamentous material, thus resembling those described in other
      mammals. Despite the large number of cells examined, only one cell showed
      evidence of a chondrocyte-like morphology in that it possessed an incomplete
      pericellular zone of microfilamentous material separating the cell membrane from
      the adjacent collagen bundles of the extracellular matrix (ECM). Thus, on
      morphological grounds, fibrocartilage was virtually non-existent in the specimens
      examined. The mean collagen fibril diameter was 43.9 nm and the fibril diameter
      distribution was not unimodal. Although the majority of fibrils had a relatively
      small diameter, two of the three specimens possessed many fibrils with diameters
      of over 100 nm, this being consistent with tissue subjected to tension. The mean
      area of a fibre bundle occupied by collagen (as opposed to the ground substance)
      was approximately 56 per cent.

PMID- 12001552
TI  - The effect of continuous intrusive force on human pulpal blood flow.
AB  - The purpose of this study was to examine the effect of continuous intrusive force
      application on human pulpal blood flow (PBF). Recordings were made of 13 vital
      upper left central incisors in 13 healthy participants (experimental group, n =
      8; control group, n = 5) who had clinically healthy tooth crowns and periodontal
      tissues. PBF was recorded by means of a laser Doppler flow meter (LDF) with an
      opaque rubber dam applied to the teeth. The basal blood flow in the pulp (BBFP)
      was compared during three observation periods: (1) before orthodontic archwire
      engagement; (2) during wire engagement (control group: no application of force;
      experimental group: continuous intrusive force of 0.5 N); and (3) after the
      removal of the wire. In the experimental group, brief intrusive forces (magnitude
      0.5, 1.0, and 2.0 N) were applied to the incisal edge of the examined teeth to
      determine their effect on acute changes in PBF. The results obtained were as
      follows: (1) the BBFP in the experimental group was significantly reduced during
      the period of continuous intrusive force application (P < 0.05), which was
      followed by recovery after the removal of the wire. (2) Brief intrusive force
      produced a significant reduction of PBF (P < 0.05), but the reduction rate
      (percentage) did not differ significantly during the observation periods. The
      results indicate that the measurement technique shown in this study could detect
      PBF change produced by continuous orthodontic force application.

PMID- 12001553
TI  - Effects of headgear Herbst and mandibular step-by-step advancement versus
      conventional Herbst appliance and maximal jumping of the mandible.
AB  - The aims of this study were to compare dental and skeletal treatment changes in
      Class II division 1 malocclusions with two modes of maxillary control and two
      modes of bite-jumping. The subjects comprised Chinese children with severe Class
      II division 1 malocclusions, i.e. 21 consecutive subjects (13.4 +/- 1.4 years)
      treated with a headgear Herbst appliance and step-by-step advancement (HHSSA) of
      the mandible, and 24 consecutive subjects (13.2 +/- 1.4 years) treated with a
      'conventional' Herbst appliance with maximal jumping (HMJ) of the mandible.
      Lateral cephalograms obtained at the start and end of treatment were analysed.
      The results showed that the improvement of the sagittal jaw relationship was
      significantly larger (2.9 mm; P < 0.001) in the HHSSA group than in the HMJ group
      due to the increased effect on the maxilla (-1.5 mm, P < 0.001) and the mandible
      (+1.4 mm, NS). There was no significant difference in the change in lower
      anterior face height, being 2.7 and 3.1 mm, respectively. The mandibular plane
      angle decreased significantly in the HHSSA group (-0.7 degree; P < 0.05) and
      increased insignificantly in the HMJ group (0.4 degree, NS), the difference being
      statistically significant (P < 0.01). The maxillary molars moved significantly
      more distally (1.1 mm, P < 0.05) and were intruded in the HHSSA group (-1.0 mm, P
      < 0.001) compared with a small extrusion in the HMJ group (+0.3 mm, NS), the
      difference being statistically significant (P < 0.001). There was no significant
      difference in the effect on the mandibular teeth. Treatment with HHSSA seems to
      result in a greater effect on the sagittal jaw relationship, improved vertical
      control and more maxillary molar movement. Mandibular anchorage loss was not
      reduced with step-by-step advancement of the mandible.

PMID- 12001554
TI  - Relationship between cranial base structure and maxillofacial components in
      children aged 3-5 years.
AB  - The aim of this study was to clarify the inter-relationships between cranial base
      angle, the morphological variations of maxillofacial components, and growth of
      the anterior cranial base length. One hundred and twenty-two Japanese children
      aged 3-5 years with normal occlusion in the primary dentition were included in
      this investigation. To analyse the relationship between cranial base structure
      and maxillofacial components, the subjects were divided into three groups
      according to facial type (prognathic, orthognathic, or retrognathic) assessed by
      the magnitude of their NSAr angle (as cranial base angle). These categorized
      cephalometric profiles suggested that the antero-posterior location of the
      maxillofacial components corresponded to the NSAr angle. Factor analysis of
      cephalometric variables showed that the variation of maxillofacial components
      from the S-N line was strongly related to the cranial base angle. This normal
      range of morphological variation was distinguished from that of growth by the
      factor loadings. From these results, theoretical models of cephalometric profiles
      with normal occlusion were computed by linear regression analysis. Using the
      models, a standard profile related to an arbitrary cranial base angle was
      obtained for children with normal occlusion, aged 3-5 years.

PMID- 12001555
TI  - The effects of reconditioning on the slot dimensions and static frictional
      resistance of stainless steel brackets.
AB  - This study investigated the effects of reconditioning on the slot dimensions and
      the static frictional resistance of stainless steel brackets at 0, 5, and 10
      degrees bracket/archwire angulation. A sample of 45 used, commercially
      reconditioned 0.018 x 0.030 inch stainless steel standard edgewise brackets was
      compared with a matched sample of 45 new brackets. The slot dimensions of 15 new
      and 15 reconditioned brackets were examined using a photomicroscope. With new
      brackets both the occluso-gingival slot width (mean = 0.0197 inch) and slot depth
      (mean = 0.0304 inch) exceeded the manufacturer's nominal dimensions of 0.018 x
      0.030 inch. The reconditioning process resulted in a further increase in slot
      width (mean = 0.0205 inch), which was statistically significant (P = 0.028), and
      a reduction in slot depth (mean = 0.0291 inch), which was highly statistically
      significant (P = 0.002). This may be attributable to preferential metal removal
      by the electro-polishing phase of the reconditioning process. Friction testing of
      30 new and 30 reconditioned brackets demonstrated that both showed an increase in
      binding effects as the bracket/archwire angulation was increased from 0 to 5-10
      degrees. However, the changes in slot dimensions secondary to reconditioning did
      not result in a statistically significant difference in mean static frictional
      resistance when the two bracket types were compared. Although the brackets were
      altered physically by the reconditioning process, their performance during
      simulated sliding mechanics was not adversely affected. This implies that
      reconditioning may not result in clinically significant effects.

PMID- 12001556
TI  - A comparative study of two mandibular advancement appliances for the treatment of
      obstructive sleep apnoea.
AB  - Mandibular advancement appliances (MAAs) are accepted as a treatment option for
      snoring and mild obstructive sleep disorders. In the present clinical study two
      differently designed devices were examined for their effectiveness in treating
      obstructive sleep apnoea (OSA). The study was based on an assessment of 26
      patients with a polysomnographic diagnosis of mild OSA [22 men, four women; mean
      body mass index 27.3 kg/m2 (SD 3.1); mean age 56.8 years (SD 5.2); mean
      respiratory disturbance index (RDI): 16.0 events/hour (SD 4.4)]. After insertion
      of the first MAA and a 6-8-week habituation period, a cardio-respiratory home
      sleep study was carried out. Following a 2-3-week period with no treatment, the
      second appliance was inserted. The sequence of the devices was randomized. Once
      the patients had become accustomed to the second appliance, another somnographic
      registration was carried out. Daytime sleepiness, snoring, and sleep quality were
      assessed subjectively on a visual analogue scale. The results showed that a
      statistically significant improvement in the respiratory parameters was achieved
      with both appliances (P < 0.01). However, the activator [RDI: 5.5 events/hour, SD
      3.3; apnoea index (AI): 3.4 events/hour, SD 2.1] was significantly more effective
      (P < 0.01) than the Silencor (RDI, 7.3 events/hour, SD 5.3; AI: 5.8 events/hour,
      SD 3.2). No difference was recorded in the subjective assessment of the
      therapeutic effects. Both appliances reduced daytime sleepiness and snoring and
      improved sleep quality, and both influenced the treatment outcome.

PMID- 12001557
TI  - The influence of maxillary gingival exposure on dental attractiveness ratings.
AB  - This study examined the influence of maxillary gingival display on the
      attractiveness ratings awarded by lay people. One hundred and twenty university
      students (94 females, 26 males) were shown seven photographs of a male and seven
      photographs of a female subject, each with varying levels of gingival display
      ranging from -2 to +4 mm. Attractiveness ratings were recorded on a 10-point
      numerical scale for each of the photographs. The photographs where the full
      height of the incisors were revealed and no gingival tissue was visible (0 mm of
      gingiva) were rated as the most attractive. Gingival display of more than 2 mm
      was rated as progressively less attractive. Linear regression analysis revealed
      that those students who had received orthodontic treatment rated the photographs
      representing the female student as more attractive than those representing the
      male (P < 0.05).

PMID- 12001558
TI  - Unilateral primary or secondary retention of permanent teeth, and dental
      malformations.
AB  - The purpose of the present investigation was to describe the dentition in
      subjects with local primary or secondary unilateral retention of two or more
      permanent teeth, and to elucidate the aetiology by comparing the regions of
      retention with the innervation pattern of the jaws. The material comprised
      radiographic dental orthopantomograms (OTP) from 12 patients with an age range of
      6-18 years (six females and six males). The locations of retention and the dental
      morphology in the affected regions were analysed. Comparison with contralateral
      teeth was undertaken and the innervation pattern of the affected field was
      considered. Varying degrees of dental root malformation were found to be
      associated with primary and secondary retention. More pronounced root
      malformations were observed in subjects with several affected teeth. A connection
      between unilateral retained permanent teeth and temporary or permanent disruption
      of the nerve supply to the affected region is suggested.

PMID- 12001559
TI  - Restrict subspecialists to their own field or risk quality problems.

PMID- 12001560
TI  - Emergency credentialing helps disaster response.

PMID- 12001561
TI  - ICU care improves with intensivists, initiatives.

PMID- 12001562
TI  - How to evaluate your staffing decisions.

PMID- 12001563
TI  - Bioterrorism watch. Traumatized health care providers may need stress counseling
      in horrific aftermath of bioterror attack.

PMID- 12001564
TI  - Bioterrorism watch. Winds of war: researchers track airborne anthrax.

PMID- 12001565
TI  - Extra, extra: HHS takes ads in newspapers to spread word. Agency plans to release
      nursing home quality initiative information via media, Web site.

PMID- 12001566
TI  - Seeking clarity. Andersen ties put providers in limbo.

PMID- 12001567
TI  - Charity's new business. Red Cross for-profit venture targets mad cow pathogens.

PMID- 12001568
TI  - And the winner is.... Patient-safety awards abound, but do they represent real
      progress in the fight against medical errors, or are they just for show?

PMID- 12001569
TI  - Doctor's orders. Computerized decision-support system directs Vanderbilt
      physicians to the latest treatment data, helping to eliminate unnecessary costs.

PMID- 12001570
TI  - Eyeing the watchdog.
AB  - The American Hospital Association and the Joint Commission on Accreditation of
      Healthcare Organizations are at it again. The AHA once more is scourging the
      JCAHO for too much work outside of its accreditation role, and this time AHA
      President Richard Davidson (left) is accusing the commission of becoming a
      government regulator of hospital business and clinical practices. But the JCAHO
      maintains that its mission remains intact.

PMID- 12001571
TI  - [Adult respiratory distress syndrome--etiology and pathogenesis].
AB  - Adult respiratory distress syndrome (ARDS) is not a specific lung disease. It
      represents an acute respiratory insufficiency syndrome in patients with non
      injured lung as a result of severe multiple lung lesions of different etiology
      and pathogenesis. ARDS is provoked by a great number of etiologic factors of two
      main groups: 1) etiologic factors directly injuring the alveolo-capillary wall
      and 2) etiologic factors indirectly injuring the alveolo-capillary wall. ARDS
      develops in three phases: phase of exudation, phase of injury of the
      alveolocapillary wall and phase of proliferation (chronic phase).

PMID- 12001572
TI  - [Dyspnea. I. Definition and pathophysiological problems].
AB  - An analytical review was made on the pathophysiological mechanisms suspected to
      be involved in dyspnea, accepting that the sensation of shortness of breathing,
      and the subjective signs (exertion, anxiety and fear) are essential for the
      diagnosis of this condition. Bearing in mind the anatomical relations in the
      central nervous system between the structures involved in the control and
      regulation of the respiration, and these involved in the emotions, a scheme was
      presented of the pathophysiological mechanisms, which determine the essential
      signs of the dyspnea. Three neuronal circuits were assumed for the explanation of
      the manifestations in dyspnea: subjective signs, symptoms of the thoraco
      pulmonary and cardio-vascular systems, and these of the voluntary muscular system
      that accompanied dyspnea.

PMID- 12001573
TI  - [Dyspnea. II. Clinical and treatment problems].
AB  - In a previous paper (Balanova, Surcheva and Ichev, 2001) we have proposed a
      scheme about pathophysiological mechanisms involved in dyspnea. Some of the
      clinical problems in dyspnea were discussed in this paper on the base of that
      scheme, as well as clinical observations on the patients with dyspnea. Two groups
      of symptoms were considered--subjective and objective, and their significance for
      the diagnosis of the dyspnea and of the disease that provokes dyspnea were
      evaluated. A critical analysis of the different forms of dyspnea has been made,
      and suggestions about the treatment of the subjective symptoms in dyspnea were
      proposed.

PMID- 12001574
TI  - [Longitudinal study of parameters of respiratory function tests and blood gas
      analysis in patients with progressive systemic scleroderma].
AB  - The longitudinal study encloses 53 patients with PSS followed up for a period of
      6 years. The most frequent changes in the parameters of pulmonary function are:
      diffusing capacity impairment--reduction in DICO (86.8% of the patients),
      restrictive lung disease pattern (50.9% of the patients) and arterial hypoxemia
      (43.4% of the patients). The duration of PSS and the follow up period do not
      cause significant changes in the pulmonary function parameters and the arterial
      blood-gas analysis in the group of patients studied.

PMID- 12001575
TI  - [Interleukins and endocrine function].
AB  - Views and experimental data on the role of interleukins in the regulation of the
      endocrine functions of hypothalamus, pituitary gland, thyroid gland, suprarenal
      gland and pancreas are presented. The role of interleukin-1 and interleukin-6 in
      the regulation of normal and pathological processes is examined. Data on cellular
      and molecular operation mechanisms of some interleukins on functions of the
      endocrine glands are included in the survey. The clarification of these
      mechanisms leads to new pharmacotherapeutical approaches to endocrine diseases
      treatment.

PMID- 12001576
TI  - [Antioxidant parameters in metabolic syndrome -- a dynamic evaluation during oral
      glucose tolerance test].
AB  - Patients with metabolic syndrome show augmented cardio-vascular risk, at least in
      part mediated through disequilibrium between mechanisms generating free radicals,
      and antioxidant defense. Carbohydrate and lipid disturbances in metabolic
      syndrome induce oxidative stress via several non fully understood mechanisms.
      Glucose overload in oral glucose tolerance test (OGTT) can also induce oxidative
      stress. The aim of our study was to evaluate changes in superoxide dismutase and
      glutathione peroxidase activity, as well as total antioxidant status in OGTT in
      patients with metabolic syndrome and in healthy subjects. OGTT was performed in
      36 healthy volunteers and in patients with metabolic syndrome. Glucose, Insulin,
      and triglycerides were evaluated at 0th, 30th, 60th, 120th, and 180th min.
      Superoxide dismutase and glutathione peroxidase were measured at 0th, 60th, and
      120th min. Total antioxidant status was measured at 0th, and 120th min. At 0th
      min total, HDL and LDL cholesterol were evaluated. A statistically significant
      decrease (p < 0.05) in superoxide dismutase activity at 120th as compared with
      60th min were observed. Glutathione peroxidase activity decreased significantly
      (p < 0.05) even though at 60th as compared with 0th min and remained decreased at
      120th min. Total antioxidant status was found to be increased (p < 0.05) at 120th
      as compared with 0th min. The observed dynamic in patients did not differed (p >
      0.05) from control group. The study shows a decrease in antioxidant enzyme
      activity and a compensatory increase in total antioxidant status, indicating a
      surcharge of antioxidant homeostasis. In context of carbohydrate and lipid
      disturbances in metabolic syndrome, this is to suggest an existing of
      complementary pathogenic mechanisms, able to aggravate cardiovascular risk in
      these patients. Correction of metabolic disturbances may be an efficacious tool
      for influencing on prooxidant-antioxidant homeostasis too.

PMID- 12001577
TI  - [Congestive heart failure--some current problems].
AB  - The congestive heart failure (CHF) has become one of the most common syndromes
      afflicting the population. The long-term prognosis of these patients is bad. The
      CHF shows a tendency toward fast progressive development. The aim of our study
      was a retrospective investigation on CHF patients, a determination of CHF
      functional class by NYHA and its type, a determination of the most important
      diseases leading to heart decompensation and of the reasons for dead in these
      patients. For a 6-year period we investigated 6428 patients. 1095 (17.03%) of
      them were with a different degree of CFH. More of them were with II and III
      functional class of CHF by NYHA. In the age decade from 61 to 70 years the
      frequency of CHF increased significantly. The most important diseases leading to
      CHF syndrome were chronic ischemic disease, arterial hypertension, COPD with
      chronic cor pulmonale and valve diseases. The average age of deceased CHF
      patients was 67.8 +/- 7.4 years. After the manifestation of the first group of
      symptoms the mean life duration of CHF patients was 13.2 +/- 4.1 years.

PMID- 12001578
TI  - [Studies on restraint ulcers in rats in conditions of acute copper deficiency].
AB  - In the present experiment, we have investigated the impact of the acute copper
      deficiency on the pathogenesis of stress ulcers' formation in rats during cold
      restraint stress. A powdered milk diet, lasting for 5 days, causes a
      significantly decrease of stomach copper content in rat, comparing to content in
      rats receiving standard laboratory diet. The severity of mucosal disturbances,
      expressed as total number and area of stress ulcers, is most prominent in animals
      receiving hypocupric diet. Their treatment with Ranitidine extends the
      morphological disturbances in the stomach mucosa and produces highest level of
      lipid peroxidation and lowest activity of superoxide dismutase in the stomach
      compared to the other groups. In conclusion, the appropriate copper balance plays
      an essential role for the natural resistance of the stomach mucosa and
      Ranitidine, in conditions of acute copper deficiency, makes deeper the
      disturbances produced by stress.

PMID- 12001579
TI  - [Comparative analysis of blood and urinary electrolytes in normotensive and
      hypertensive normal, overweight and obese subjects aged 50-54 in the Bulgarian
      army].
AB  - Objective of the study is to investigate the hypotheses regarding the correlation
      of serum levels and urinary excretion of electrolytes with arterial hypertension.
      211 subjects aged 50-54 from Bulgarian Army were studied. Evaluated were
      following parameters: SBP, DBP, BMI, Na+, K+ in blood serum; Na+, K+, NaCl, KCL,
      Na/K ratio, Ca++, Mg++ in 24-h urine excretion. Statistical analysis of variance,
      dispersion and correlation analysis (using 6D program from statistical pack BMDP)
      were applied. In the blood, no correlation was found between Na+ and both SBP and
      DBP. A significant positive correlation between SBP and K+ was found only in non
      obese hypertensive females (R = 0.59, p < 0.05). Correlation between K+ and DBP
      was negative in separate groups with normal BMI (R = -0.84, R = -0.65, p < 0.05).
      In the 24-h urine excretion, no correlation was found between K+, NaCl, KCL and
      SBP, as well as between Na+ and SBP and DBP. Significant positive correlation was
      found between K+ and DBP in obese hypertensive subjects (R = 0.56, p < 0.05) and
      between NaCl and DBP (R = 0.47 up to R = 0.66 in separate groups, p < 0.05).
      Significant positive correlation between Ca++ and DBR (R = 0.47) was found in
      obese hypertensives. Mg++ correlates positively with DBP (R = 0.62 in some
      groups). Urine levels of Ca++ and Mg++ were significantly higher in
      normatensives. Electrolytes in blood and urine were closely related to DPB rather
      than to SBP. K+ levels in blood affect only DBP. Our data do not confirm the
      hypothesis for the positive correlation between urinary Na(+)-excretion and BP
      (except in obese subjects). The hypothesis about the inverse relation of K(+)
      intake to BP, especially to DBP is confirmed by our data. The data regarding the
      Ca++ and Mg++ urinary excretion and their correlation with DBP and SBP are very
      discordant and do not give an opportunity to make definite conclusions. Our data
      confirmed the hypothesis about the natriuretic effect of Mg++, which possibly is
      of a protective value for development of AH in some obese persons.

PMID- 12001580
TI  - [Telemetric intramedullary nail lengthens bones by traction. Longer legs during
      sleep (interview by Michael Koczorek)].

PMID- 12001581
TI  - [Minor rhinitis. Consequent therapy protects against asthma].

PMID- 12001582
TI  - [Fluorescent endoscopy superior to white light endoscopy. Detecting cancers of
      the urinary bladder earlier].
AB  - 5-aminolevulinic acid-induced fluorescence endoscopy (AFE) has enormously
      increased the effectiveness of early cancer detection. This was first shown for
      cancer of the bladder. After application of 5-aminolevulinic acid (5-ALA)
      endogenous protoporphyrin IX (PP IX) accumulates in tumor tissue. When such
      tissue is then irradiated with blue light, the neoplastic areas can be identified
      by red fluorescence and, in the case of the bladder, can be removed by
      transurethral resection (TUR) or laser coagulation in the same endoscopic
      session. The great advantage of this highly sensitive technique (95%) is to be
      seen in particular in the detection of flat urothelial neoplastic lesions--until
      recently a deficit in conventional white-light endoscopy. Initial investigations
      show that improved early detection and the reduction in the residual tumor rate
      lead to longer recurrence-free intervals.

PMID- 12001583
TI  - [Tumors of the mouth cavity. Not all fluorescent tumors are malignant].
AB  - Early diagnosis and treatment of malignant tumors of the mouth and throat can
      greatly improve survival rates. Diagnostic fluorescence permits the reliable
      detection not only of oral cancer, but also of cancer precursor lesions. A
      problem here is the fact that although carcinomas can be detected with a high
      level of sensitivity, our own studies also demonstrate a considerable false
      positive rate (35%). Possible reasons for this currently being considered are non
      compliance by the patient with the required fasting period, poor mouth hygiene
      and the state after radiation therapy to the face. Under these circumstances,
      patient management is of particular importance.

PMID- 12001584
TI  - [Early detection of gastrointestinal tumors. Guided biopsy with fluorescence].

PMID- 12001585
TI  - [Atherosclerotic renal artery stenosis].
AB  - Only patients with the typical symptoms of a stenosis of the renal artery should
      be submitted to a screening examination. In elderly patients with suspected
      atherosclerotic stenosis of the renal artery, color-coded duplex ultrasonography
      is the diagnostic method of choice. If visualization proves to be poor, and in
      particular when accessory renal arteries are present, magnetic resonance
      angiography may be considered. If there is significant stenosis of the renal
      artery, and if a positive effect on renal function or blood pressure control is
      to be expected, percutaneous transluminal angioplasty with implantation of a
      stent is the treatment of first choice. In the case of patients with additional
      aortic pathology, operative revascularization must be considered.

PMID- 12001586
TI  - [Increased renal retention values in general practice. Creatinine and urea too
      high--what should be done].

PMID- 12001587
TI  - [Bacterial infections of the respiratory tract and of the ENT area. Cephalosporin
      in general practice is effective].

PMID- 12001588
TI  - [Principles and general ultrasound practice. Diseases of the neck soft tissues].

PMID- 12001589
TI  - [Arthrosis drugs critically evaluated. Emphasis on cartilage protection].

PMID- 12001590
TI  - [Bilateral metatarsal fractures. What caused the pain in this housewife?].

PMID- 12001591
TI  - [Effective reduction of the HbA1c level, fewer side effects. First fixed
      combination for type 2 diabetic patients].

PMID- 12001592
TI  - [Triptanes are still effective in the middle of a migraine attack. Best effect
      before reaching high point].

PMID- 12001593
TI  - [Effect of proton pump inhibitors. In vivo is decisive].

PMID- 12001594
TI  - [Bronchial asthma. Dual problem--dual therapy].

PMID- 12001595
TI  - [Which diuretic in heart failure? For the prognosis, they are not all equal].

PMID- 12001596
TI  - [Patients need no longer plan meals. Colitis therapy is simplified].

PMID- 12001597
TI  - Early catheter removal after transurethral resection of the prostate.
AB  - INTRODUCTION: Post-operative care of transurethral resection of the prostate
      (TURP) includes prolonged bladder irrigation that places a heavy burden on the
      nursing staff and a substantial strain on the budget. There is a trend towards
      early catheter removal after TURP even to the extent of performing it as a day
      case. We explored the feasibility and limitations of early catheter removal after
      TURP in our unit. DESIGN: Prospective study. SETTING: Department of Urology, The
      National Hospital of Sri Lanka (NHSL), Colombo. PATIENTS AND METHODS: The study
      was in a tertiary referral centre (NHSL), on 65 patients with a mean age of 67.5
      years who underwent TURP for mild to moderate enlargement of the prostate, less
      than 25 g, with lower urinary tract symptoms. Post-operative irrigation was
      maintained by diuretics at operation or a short term saline irrigation in the
      operating theatre. RESULTS: 17 patients developed clot retention in the ward that
      was managed by irrigation for 12 to 24 h. 62 patients who had clear or minimally
      blood-stained urine were tried without catheter after 24 h. Only two failed to
      pass urine. Patients without other complications were discharged from hospital
      after 1 or 2 successful voidings on the same day. There were no readmissions with
      complications. CONCLUSIONS: This study supports the feasibility of early catheter
      removal after a short irrigation period in TURP in the majority of patients with
      mild to moderate enlargement of the prostate without significantly increasing
      post-operative complications.

PMID- 12001598
TI  - Psychological distress among students from five universities in Sri Lanka.
AB  - OBJECTIVE: To determine the proportion of university students that are
      psychologically distressed when compared to an age and sex matched population
      sample and to describe the factors that may contribute to their distress. DESIGN:
      A cross-sectional comparison study. METHODS: The general health questionnaire
      (GHQ 30), previously validated in Sinhala, was administered as a screening test
      to random samples of undergraduates in 5 universities. Age and sex matched
      controls from the respective communities were also administered the screening
      test. The undergraduates also filled in a pre-tested questionnaire with personal
      details. Chi-square tests were used to determine statistical significance between
      groups. RESULTS: Among the undergraduates, 104 (39.8%) had scores for
      psychological distress whereas only 67 (25.7%) from the community sample had
      scores for similar distress. This difference was significant (p = 0.0007). A
      significantly greater proportion (p = 0.009) of those entering from rural schools
      were psychologically distressed than those from suburban and urban schools, and a
      greater proportion living in rented rooms and hostels were (p = 0.001) distressed
      than those travelling from their homes. CONCLUSIONS: The psychological distress
      among undergraduates was significantly greater than among the general population.
      More students who enter from rural schools seem to be distressed than those who
      enter from suburban and urban schools.

PMID- 12001599
TI  - The swollen leg: is it deep vein thrombosis? The experience of a tertiary
      referral center in Sri Lanka.
AB  - INTRODUCTION: The role played by deep vein thrombosis (DVT) as a cause of leg
      swelling in Sri Lanka is unknown. PURPOSE: To study the prevalence of proximal
      DVT, value of risk factors and clinical features and attitudes of clinicians
      towards diagnosis and treatment of DVT among those presenting with leg swelling
      as the main complaint. DESIGN: Prospective consecutive referrals to the
      University Surgical Unit, Colombo, over 10 months starting in January 1998.
      INCLUSION CRITERIA: DVT suspects with swollen legs. EXCLUSION CRITERIA: Varicose
      veins, leg ulceration and generalized oedema. METHODS: Color duplex scanning of
      the proximal deep veins and the superficial veins to detect occlusion and reflux.
      Information on previous diagnoses and treatment were obtained from the medical
      records. RESULTS: 63/137 (45%) had deep venous causes for oedema. Fever with
      rigors and inguinal lymphaedenopathy were strongly predictive of non DVT causes.
      Filariasis is the first diagnosis and DVT is considered late among the
      outpatients. CONCLUSIONS: DVT is a common cause of leg swelling among those
      referred.

PMID- 12001600
TI  - Adverse drug reactions: monitoring, reporting and prevention.

PMID- 12001601
TI  - Polycystic ovary syndrome and its relevance to women from south Asia.

PMID- 12001602
TI  - Removal of severely encrusted forgotten ureteral stents by minimal access
      techniques.

PMID- 12001603
TI  - An intrauterine device in the bladder mimicking urinary tract infection.

PMID- 12001604
TI  - Primary spontaneous complete colporrhexis.

PMID- 12001605
TI  - Internal jugular vein phlebectasia.

PMID- 12001606
TI  - A case of sarcoidosis.

PMID- 12001607
TI  - Mucinous adenocarcinoma of the prostate gland.

PMID- 12001608
TI  - Accuracy of cause of death in hospital death declaration forms.

PMID- 12001609
TI  - Pilot study of a low-cost CLO test.

PMID- 12001610
TI  - Lack of granuloma formation in tuberculous lymphadenitis--clue to the diagnosis
      of human immunodeficiency virus infection.

PMID- 12001611
TI  - Viral myositis caused by Epstein-Barr virus (EB virus) in children.

PMID- 12001612
TI  - Screening for diabetes mellitus in pregnancy.

PMID- 12001614
TI  - Lymphoma, thyrotoxicosis and thymic hyperplasia.

PMID- 12001615
TI  - Seroconversion after hepatitis B vaccination in healthy young adults, and the
      effect of a booster dose.
AB  - OBJECTIVE: Previous studies have shown that 5% to 15% of healthy people do not
      show a protective antibody response following hepatitis B vaccination. The study
      was done to determine the protective efficacy of vaccination in healthy young
      adults 1 to 4 years after the three dose vaccination series and to study the
      effect of a booster dose on non-responders and hypo-responders. DESIGN:
      Prospective intervention study. SETTING: From January to June 2000, Faculty of
      Medicine, University of Colombo. STUDY GROUP: 258 volunteers from five batches of
      medical students vaccinated with three doses of the recombinant vaccine at 0, 1
      and 6 months. RESULTS: 9.5% were non-responders. Duration of vaccination, sex and
      body mass index were not significantly associated with anti-HBs levels. 28.6% had
      potential risk factors for acquiring HBV infection. 86.3% of non-responders
      developed protective anti-HBs titres after a booster dose. The persistent non
      responders did not have a chronic illness or past HBV infection. CONCLUSIONS: A
      substantial number do not seroconvert after hepatitis B vaccination. Testing of
      blood for anti-HBs one month after vaccination is recommended to recognise non
      responders as a booster dose will be beneficial in the majority of them.

PMID- 12001616
TI  - Megaselia scalaris (Diptera: Phoridae) can live on ripe bananas--a potential
      health hazard?
AB  - OBJECTIVE: Identification of larvae that inest bananas and investigating its
      habits. DESIGN: Laboratory based study. SETTING: Department of Parasitology,
      Faculty of Medicine, University of Colombo. METHODS: Bananas brought to the
      department with a query of maggot infestation were examined and the presence of
      maggots was confirmed. Maggots were allowed to develop into adults. The larvae
      and the flies were identified using standard keys. RESULTS: Megaselia scalaris
      was identified, the larvae of which infest ripe bananas. Three generations of M
      scalaris were reared using ripe bananas as the only source of food. Two other
      banana specimens yielded larvae that eventually grew into adult flies of
      Bactrocera species. CONCLUSIONS: In addition to Bactrocera spp. larvae of which
      are known pests in bananas, M scalaris larvae were detected as pests for the
      first time. We demonstrated that M scalaris can complete its life-cycle depending
      on ripe bananas as the only source of food. The vast consumption of bananas and
      the potential of M scalaris to cause intestinal and wound myiasis in humans make
      these findings medically important.

PMID- 12001617
TI  - Transformation via Novation. Online marketplace helps simplify the materials
      management process.

PMID- 12001618
TI  - A dot-com survivor still bets on the Net.

PMID- 12001619
TI  - VHA's ongoing challenge: relevance.

PMID- 12001620
TI  - Making healthcare quality a team effort.

PMID- 12001621
TI  - Working on a vision, mission. Growth, changes and challenges have been constants
      during VHA's first quarter-century.

PMID- 12001622
TI  - Beyond group purchasing. VHA expands services in effort to keep clinical quality
      at the forefront.

PMID- 12001623
TI  - [How to do an information search on the Internet using a search engine?].

PMID- 12001624
TI  - [Contribution of the generalist nurse to the promotion of patient education].

PMID- 12001625
TI  - [Criteria of scientific validity in research].
AB  - The purpose of this article is to present the evaluative criteria of qualitative
      and quantitative research. Philosophical foundations of positivism,
      postpositivism and constructivism are explored. Triangulation and crystallization
      expose the controversies about them. Finally, Lincoln and Guba criteria are
      retained for the evaluation of qualitative and quantitative research.

PMID- 12001626
TI  - [Illness Intrusion Rating Scale: validation of the French version].
AB  - The IIRS is rating scale, useful in research and clinically, measuring the
      importance of illness intrusion of its treatment on the patient's quality of life
      or that of the family.

PMID- 12001627
TI  - [Virginia Henderson: 1897-1996. Biography and analysis of her work].

PMID- 12001628
TI  - [French validation of the revised Piper Fatigue Scale].
AB  - The need for a valid and reliable multi-dimensional instrument in French to
      enable nurses and clinicians to assess intensity and changes in cancer-related
      fatigue (CRF) and evaluate efficacy of intervention strategies on patient
      outcome, prompted us to translate the Piper Fatigue Scale (PFS) and assess its
      psychometric properties in a French speaking population. The revised PFS is a 22
      item self-report instrument with four sub-scales: behavioural/severity,
      affective, sensory and cognitive/mood. The PFS was translated using a procedure
      of translation and back translation and tested on 20 bilingual subjects.
      Correlation coefficients were measured between the item scores of the English and
      French version of the PFS. The French version of the PFS was adjusted and then
      completed by 229 adult cancer patients with solid tumours under-going treatment
      by chemo-, radio-, hormono- or immunotherapy. A factorial analysis and a multi
      traits analysis were used to assess the reliability and the dimensional structure
      of the translated version of the PFS. Cronbach's alpha correlations ranged
      between 0.85 and 0.92 for the various sub-scales, thus indicating good sub-scale
      reliability. Item internal consistency was good with 100% of item-scale
      correlations greater than or equal to 0.4. Item discriminant validity checking
      showed 3 items to be insufficiently discriminating. Item-scale correlations
      greater than the correlation of the item with other sub-scales were 98%. The
      Cognitive/Mood dimension appeared to group 2 separate dimensions. Convergent
      validity, tested by correlating the PFS with a Visual Analogue Scale measuring
      fatigue and with the OMS Physical Performance Status Scale, revealed significant
      relationships. A five sub-scale model of the PFS is proposed containing 22 items
      to increase performance of the French version of the PFS comparatively to the 4
      sub-scale model of the original PFS. Translation of 2 items has been slightly
      modified to reduce ambiguity. The overall results of this preliminary study are
      satisfactory. We expect results to be further improved by the modifications
      proposed and testing is now underway in homogenous populations to evaluate the
      sensitivity of the instrument to changes over time. This will enable us to
      ascertain the definitive French version of the Piper Fatigue Scale.

PMID- 12001629
TI  - [Second year nursing students' identity crisis. "Assessment of objectives"].
AB  - Nursing students, guided by aspirations, begin training with an idealized
      representation of the profession, and the experiences they will encounter during
      their studies will vary progressively. Nursing training is based initially on a
      pedagogical system alternating between the classroom and the work place, exposing
      the student to a variety of situations. This process of work experience during
      the three years of study is marked by a crisis period during the second year.
      This involves an identity crisis resulting in a change of objectives. The
      analysis indicates that this is structural. The beginning of the second year is
      characterised by the student's confrontation with the theoretical and practical
      applications of the course. It is the result of a year's experience and
      instruction, which puts into question the student's vision, beliefs, and the
      orientation towards a new conception of himself/herself and of the world. The
      realisation of an incongruity, this reality check, is followed by a feeling of
      deception. This conflict, common in the second year, must be recognised in order
      to avoid further compromise to the identity's transformation. As soon as the
      student finds himself/herself committed to a training program that does not
      contribute to the realisation of his/her objectives, the feeling of being thrown
      off balance in relation to his/her point of reference increases, and the end
      result will be absenteeism or opposition. The handling of this identity crisis,
      as well as the motivational procedure, implies a modification in the quality of
      the instructor and in our way of thinking and acting. Are we adequately prepared
      to manage this crisis? Do we have access to the theories needed to resolve this
      cognitive conflict?

PMID- 12001630
TI  - [Education in research: presentation of a memory alternative at the end of
      training].

PMID- 12001631
TI  - [The perineum should not be cut].

PMID- 12001632
TI  - [The psychiatrist, the patient and the relative].

PMID- 12001633
TI  - [Beta blockers reduce cardiac complications in patients undergoing surgery].

PMID- 12001634
TI  - [Possibilities to treat urinary incontinence in women surgically have improved].

PMID- 12001635
TI  - [Treatment chain].

PMID- 12001636
TI  - [Why did the child not gain weight?].

PMID- 12001637
TI  - [The psychotic patient, the physician and the relative].

PMID- 12001638
TI  - [Progressing unconsciousness in a young male].

PMID- 12001639
TI  - [Pitfalls of the patch tests].

PMID- 12001640
TI  - [Upper abdominal pain as a souvenir from the US trip].

PMID- 12001641
TI  - [The reflux disease- an underdiagnosed problem].

PMID- 12001642
TI  - [Why do we have heartburn--the etiopathogenesis of reflux disease].

PMID- 12001643
TI  - [Diagnosing the reflux disease].

PMID- 12001644
TI  - [Drug therapy of reflux disease].

PMID- 12001645
TI  - [Surgical treatment of reflux disease].

PMID- 12001646
TI  - [Barrett esophagus and inflammation of gastroesophageal junction].

PMID- 12001647
TI  - [Malign complication of gastroesophageal reflux: adenocarcinoma of esophagus and
      gastric cardia].

PMID- 12001648
TI  - [Safe use of anti-inflammatory analgesics].

PMID- 12001649
TI  - Role of inflammatory factors in neurodegeneration.

PMID- 12001650
TI  - Botulinum toxin for treatment of parkinsonian sialorrhea.
AB  - AIM: Sialorrhea is one of the main problems of patients with Parkinson's disease
      (PD). Most of the medications used for the treatment of it are ineffective. We
      decided to try in such patients local injections of botulinum toxin, type A, into
      both parotid glands. MATERIAL: 11 patients with clinical diagnosis of idiopathic
      PD and drooling assessed as at least 2 point on the UPDRS part II and 14 control
      subjects. METHODS: Salivation was measured by weighting dental rolls before and 2
      minutes after insertion at 6 places of highest secretion of saliva in mouth
      (buccal vestibule, and sublingual area). PD patients were assessed before and one
      week after injections of 5 units of BOTOX into each parotid salivary gland and
      the results were compared to the salivation of controls. RESULTS: Average
      excretion of saliva in PD patients was significantly higher than in controls 
      0.39 +/- 0.4 g/2 min. (range: 0.02-1.82) vs. 0.19 +/- 0.16 g/2 min. (range: 0.02
      0.98) (p = 0.03). After the treatment the average excretion of saliva in PD
      patients decreased to 0.25 +/- 0.26 g/2 min. (range: 0.004-0.99) and did not
      differ significantly from controls. All patients improved also according to
      UPDRS. No side-effects were observed in any of the patients injected. CONCLUSION:
      Botulinum toxin may be an effective and safe treatment of parkinsonian
      sialorrhea.

PMID- 12001651
TI  - Phenotype and genotype correlation in childhood spinal muscular atrophy.
AB  - In the period 1998-2000 almost all new cases of childhood spinal muscular atrophy
      (SMA) in addition to those from our database were studied for possible deletion
      of SMN gene (exons 7 a 8) and NAIP (exons 5 a 6). We correlated the size of
      deletion with the type, course and the onset of disease. The most informative for
      diagnosis was deletion of SMN. NAIP was deleted only in 18% of all cases, usually
      in SMA1 (in only 2 cases of SMA2). The molecular genetics permits to come back to
      previously posed question about the extremely frequent intrafamilial variability
      in SMA families. The problem became more clear due to our knowledge on telomeric
      and centromeric copies, as well as various genes and paragenes involved in SMA
      region. In the premolecular era we postulated the gender influence on course of
      the disease, which is particularly evident in mild SMA form 3b. Interestingly,
      presently we and some others detected deletion similar to those in the patients
      among the clinically healthy siblings. Those siblings are mostly females. The
      other problem, byproduct of molecular genetic, is the occurrence of SMN deletion
      in some disorders till now considered entirely different from SMA, e.g.,
      arthrogryposis, congenital hypomyelinating neuropathies of newborn.

PMID- 12001652
TI  - Evaluation of cholinergic treatment in demented patients by P300 evoked related
      potentials.
AB  - Centrally acting cholinesterase inhibitors (ChEls) improve cognitive functions in
      Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment
      efficacy is based mainly on subjective assessment tools which includes
      standardized neuropsychological tests. Therefore, an additional objective tool
      for the evaluation of drug response is necessary. Thirty two patients were
      treated with ChEls for dementia (tacrine 19, donepezil 5, rivastigmine 8).
      Cognitive response was assessed before ChEls (baseline) and after 26 weeks, as
      optimal tolerated doses were achieved and maintained (endpoint). Evaluation
      included repeated measurements of Mini Mental State Examination (MMSE), ADAS-cog
      and P300. For statistical analysis we used ANOVA with repeated measures and
      Pearson correlation coefficient. Results demonstrated improvement of mean ADAS
      cog by 2.0 points (from 29.4 to 27.4 p = 0.08) while MMSE remained almost
      unchanged (20.1 to 19.8). Mean P300 latency reduced significantly by 24 msec
      (from 383 msec to 359 msec, p = 0.0001) thus reflecting the clinical improvement.
      However mean amplitudes did not change from baseline to endpoint (13 microvolts).
      Significant correlation was found between mean ADAS-cog and mean P300 latency at
      baseline and end-point (R = 0.452 p = 0.014, R = 0.567 p = 0.001 respectively).
      Strong correlation was found between mean MMSE and P300 latency at Baseline (R = 
      0.335 p = 0.07), and significant correlation was found at endpoint (R = -0.613 p
      < 0.001). Our data suggests that P300 is a reliable instrument for assessment of
      cognitive response to ChEls in demented patients.

PMID- 12001653
TI  - Laboral outcome after acute unilateral vestibulopathy.
AB  - Sixty-five adult patients who had acute peripheral vestibulopathy (APV) were
      followed-up to determine their functional outcome. During the acute phase, they
      were treated with betahistine and mobilization. In the entire study population,
      APV was not significantly associated with a change in occupational activities,
      physical work or driving ability. Older individuals had significantly attributed
      a change in work to disease other than APV. Change attributed to APV occurred
      significantly more frequently in women than in men. The therapeutic approach
      seems beneficial.

PMID- 12001654
TI  - TCD and the Diamox test for testing vasomotor reactivity: clinical significance.
AB  - Transcranial Doppler sonography has become widely used in assessing cerebral
      vasomotor reactivity which provides information regarding cerebral autoregulation
      and collateral circulation. Cerebral vasomotor reactivity is defined as a shift
      between cerebral blood flow or cerebral blood velocity before and after
      administration of a potent vasodilatory stimulus test. Three such tests are
      currently used for this purpose: the apnea test, CO2 inhalation and the Diamox
      test (i.v. acetazolamide), all of which are based on the dilatatory response of
      cerebral blood flow to hypercapnia. Certain advantages of the Diamox test were
      described, but each of the three tests has its strong and weak points, and this
      will be the topic under discussion. There are several practical applications of
      the combined TCD and the vasodilatory tests in assessing of cerebral vasomotor
      reactivity: 1. To evaluate the intracranial hemodynamic status in patients with
      carotid occlusive disease with the intent of predicting the occurrence of
      ischemic brain events. 2. To compare intracranial hemodynamics before and after
      carotid endarterectomy. 3. To compare autoregulation and collateral circulation
      in the different parts of the circle of Willis. 4. To predict dementia after
      stroke. In summary, the potential clinical usefulness of combined TCD and
      provocative vasodilatory tests has been clearly shown. Further large scale
      studies are needed in order to augment the applications of cerebral vasomotor
      reactivity assessment in the clinical setting.

PMID- 12001655
TI  - Paroxysmal locomotion gait disturbances in Parkinson's disease.

PMID- 12001656
TI  - The role of glutamatergic transmission in the pathogenesis of levodopa-induced
      dyskinesias. Potential therapeutic approaches.
AB  - Dyskinesias are the most frequent adverse effect of chronic levodopa therapy in
      patients with Parkinson's disease (PD). Current pharmacological treatment for
      this problem is unsatisfactory. Recently, there is evidence for the role of
      glutamate in the basal ganglia neuronal circuitry in the generation of
      dyskinesias. If indeed glutamatergic overactivity beyond the dopaminergic
      synapses plays a role in the pathogenesis of these involuntary movements, there
      is hope that its suppression may be beneficial without causing loss of levodopa
      efficacy and parkinsonian deterioration. Indeed, NMDA receptor antagonists such
      as amantadine and dextrometorphan can reduce such dyskinesias. We tested the
      efficacy of riluzole, an inhibitor of glutamatergic transmission in the
      inhibition of levodopa-induced dyskinesias.

PMID- 12001657
TI  - Failure mode and effects analysis: future tool for healthcare worker safety.

PMID- 12001658
TI  - [Facial pains as symptoms of mental disorders].
AB  - One hundred seventeen patients, aged 16-75 years, with orofacial pains were
      studied. Borderline psychic disorders were detected in 106 cases, schizophrenia-
      in 11 cases. Facial pain was characterized by (1) polymorphism of sensations
      changing their site and duration, (2) absence of orofacial sensory deficits, (3)
      symptoms "mosaic"--a combination of separate signs specific for various "organic"
      facial pain, (4) absence of objective changes in oral cavity and facial region,
      (5) key role of psychoemotional factors in pain recurrence and intensification,
      (6) non-opioid analgesics and carbamazepine inefficacy. A systematics for facial
      pains of psychic genesis, comprising two groups of disorders, was elaborated. The
      first group includes facial pain and odontalgia in borderline psychic disorders-
      neurotic (somatoform, hypochondriac and hysteric) disorders, affective ones (mild
      depressive episodes and dystimia) and paranoic personality disorder. The second
      group comprises orofacial cenesthopathies in neurotic-like (schizotypal
      disorders) and paranoid types of schizophrenia.

PMID- 12001659
TI  - [The efficacy of microsurgical remove of lumbar disc hernia].
AB  - A follow-up study of 410 patients operated for discogenic lumbar spine damages
      was conducted. Peculiarities of the disease clinical course and postoperative
      dynamics of basic symptoms studied during 1-7 years are presented. The principles
      of microsurgical reconstructive neurodecompression, including neural membrane
      reconstruction and surgery results, are demonstrated.

PMID- 12001660
TI  - [Dynamics of higher mental functions in surgical therapy of internal carotid
      artery stenosis].
AB  - To reveal typical changes of higher mental functions in patients with
      atherosclerotic lesion of internal carotid artery and to estimate influence of
      operative and non-operative treatment of carotid stenosis upon cognitive
      function. 42 patients who had undergone carotid endarterectomy (CEA) due to high
      grade carotid stenosis, and 31 patients treated conservatively were examined. A
      battery of neuropsychological tests was used to evaluate a state of higher mental
      functions. The neuropsychological syndrome in patients with carotid stenosis
      manifests with impairment of verbal and visuospatial memory, attention, disorders
      of impressive speech and constructive praxis. The degree of cognitive impairment
      was most severe in patients with bilateral stenosis. CEA performed at early
      stages of cerebral ischaemia has beneficial effect on cognitive functions. Non
      operative treatment and late CEA do not prevent further cognitive decline in
      patients with carotid stenosis.

PMID- 12001661
TI  - [Eprosartan mesylate in controlling of blood pressure in patients with ischemic
      stroke].
AB  - In 20 patients with ischemic stroke and moderate or severe arterial hypertension
      the effectiveness of eprosartan mesilat (Teveten, Solway Farma, Germany) for a
      period of 6 months was studied. Patients received 600 mg of eprosartan mesilat
      daily and in 4 cases hydrochlortyaside was also added. Monotherapy with
      eprosartan mesilat was effective in all patients with moderate arterial
      hypertension and in 43.6% in patients with severe arterial hypertension. Therapy
      with eprosartan mesilat was associated with significant hypotensive effect (more
      evident in patients with high systolic blood pressure), improvement in 24-hour
      blood pressure profile and quality of life, and lower probability of secondary
      stroke. Side effects were not observed.

PMID- 12001662
TI  - [Blood infrared spectrometry in progressive myodystrophy].
AB  - Twenty four patients with various progressive myodistrophy (PMD) types have been
      examined. Initial and follow-up blood counts, using infrared spectrometry, were
      carried out. All the patients had phospholipid dysbolism. Its level positively
      correlated with myodistrophy severity. Phospholipid level decrease was associated
      with membrane permeability increase. The authors consider phospholipid
      dysfunction as one of the key PMD pathogenetic mechanisms. Blood infrared
      spectrometry is recommended for PMD severity determination, in diagnosis and
      therapy which is pathogenetically substantiated.

PMID- 12001663
TI  - [Diagnostic significance of the type of in vitro interaction between blood
      lymphocytes and serotonin in multiple sclerosis].
AB  - The method for laboratory diagnosis of multiple sclerosis (MS)--the loading
      serotonin test in vitro based on a specific type of interaction between MS
      patient's blood lymphocytes and serotonin--is suggested. An examination of 56 MS
      patients, 12 patients with vertebrale nervous system pathology, 33 patients with
      MS phenocopies and 19 healthy subjects revealed an initial low serotonin rosette
      forming cell (RFC) content in MS patients, comparing to all the subjects studied.
      In contrast to healthy subjects and patients with other neurological disorders,
      serotonin receptor lymphocyte expression in MS patients does not change during
      serotonin stimulation in vitro and serotonin RFC number does not increase. The
      type of interaction is specific and selective, being confirmed in reaction of
      rosette-formation by serotonin excess and by the results of rosette-formation
      reaction with other biologically active components (histamine, nor adrenaline). A
      serotonin reception inhibition, specific for MS, can be determined already in the
      disease debut, regardless of patient's gender and age, clinical type, disease
      stage and duration, which proves to be of most importance. The loading serotonin
      test indexes are significant for differential diagnosis. The method patented in
      1999 is realized in vitro, excludes a double blood collection that reduces
      allergy and infection danger for patients is easy to make and cost-effective.

PMID- 12001664
TI  - [Clinical and neurophysiological features and outcome prognosis criteria of
      Guillain-Barre syndrome in children].
AB  - Clinical and electroneuromyographical (ENMG) study of 24 children with Guillain
      Barre syndrome (GBS) was conducted. Using ENMG, axonal and demyelinating GBS
      variants differing by course and rehabilitation time were distinguished. To
      predict a development of bulbar and respiratory disorders and to evaluate their
      severity and duration, diaphragm and adductive nerves conduction was
      investigated. Factors influencing motor function rehabilitation rate in GBS were
      the following: mean distal M-response amplitude during peroneal nerve
      stimulation, proximal to distal amplitudes ratio, M-response amplitude for
      femoral nerves. Three types of ENMG parameter rehabilitation in children with GBS
      (linear, stepped and undular) which characterize different rates of
      rehabilitation process are described.

PMID- 12001665
TI  - [Clinical and psychophysiological characteristics of headache in childhood].
AB  - Complex clinical psychophysiological as well as neurophysiological examinations
      of 210 children with migraine, chronic tension headache (CTH) and chronic
      posttraumatic headache (CPH) were carried out. Detailed comparative description
      of cephalalgia types is presented. In a CPH structure, predominates CTH (77.5%),
      combined type (14.1%); migraine (5.7%) and cervicogenic cephalalgia (2.7%) occur
      less often. CPH development mechanisms do not principally differ from non
      traumatic cephalalgia pathogenesis. Trauma plays a role of a non-specific trigger
      in realization of these mechanisms. Chronic cephalalgia is caused mainly by poor
      social and psychological factors and patient's personality peculiarities.
      Psychovegetative syndrome in children with CTH, migraine or CPH reflects non
      specifically diencephal structure disintegration; its clinical signs depending
      more on child's age than on cephalalgia type.

PMID- 12001666
TI  - [Linkage sib-pair analysis of dopamine receptor D2 gene Taq1A and Taq1B
      polymorphism and schizophrenia].

PMID- 12001667
TI  - [A case of brain damage cause by high-energy proton flow].

PMID- 12001668
TI  - [Munchausen syndrome].

PMID- 12001669
TI  - [Complications of therapy of advanced stages Parkinson's disease and possible
      approaches to their correction].

PMID- 12001670
TI  - [Semantic study of "play" in the structure of persecution delusion].

PMID- 12001671
TI  - [The influence of personality on clinical appearance and development of herpetic
      infection].

PMID- 12001672
TI  - [Clinical, pathophysiological and neuropathological aspects of a remote period of
      closed brain injury].

PMID- 12001673
TI  - [Activity of Scientific Board of Neurology in 1998-2001].

PMID- 12001674
TI  - [The state with the predominance of obsessive-compulsive disorders in the
      structure of childhood onset schizophrenia].
AB  - Sixty inpatients, aged 7 to 15 years, with obsessive-compulsive disorders (OCD)
      have been examined. The inclusion criteria comprised diagnostic ICD-10 criteria
      for OCD (F42), schizophrenia childhood type (F20.83) and neurotic-like
      schizophrenia (F21.3). Patients with organic CNS disorder signs and marked
      somatic pathology were excluded from the study. According to clinical features of
      the disease and its course (disease progressiveness), three OCD types have been
      determined: OCD in the structure of affective and neurotic-like spectra disorders
      (type 1); OCD in the structure of paranoid spectrum disorders (type 2); OCD in
      the structure of states with prevail of "acquired" affective and negative
      disorders (type 3). Consideration of OCD types in childhood schizophrenia and the
      disease course allows to predict severity of negative changes and remissions that
      facilitates an adequate determination of the patients' adaptive potential.

PMID- 12001675
TI  - [Surgical policy for patients with prolonged esophageal burn strictures].
AB  - Concept of early radical surgical treatment of prolonged esophageal burn
      strictures (PEBS) is presented. From 1980 to 2000 one-stage esophagoplasty was
      performed in 503 (62.0%) of 811 patients with PEBS. Bouginage was effective in
      17.2% patients. Extirpation of the esophagus with posteriormediastinal plastic
      repair was performed in 119 patients. Mean age of patients was 48 years, mean
      anamnesis time--11 years. 13 (10.9%) patients had total PEBS. Combined burn of
      the stomach was revealed in 25 (21.0%), of the pharynx--in 4 (3.4%) patients.
      Isoperistaltic gastric tube was used in 102 (85.7%) patients, whole stomach--in 1
      (0.8%), left half of the large intestine (antiperistaltic)--in 16 (13.4%)
      patients. Esophagectomy was performed transiatally in 114 (95.8%), from three
      approaches (+ right-sided thoracotomy)--in 5 (4.2%) patients. Transplant on the
      neck was connected with esophagus in 106 (89.1%) patients, with the pharynx--in
      13 (10.9%). Combined operations were performed in 14 (11.8%) patients.
      Intraoperative complications were in 6 (5.0%), postoperative--in 39 (33.0%)
      patients. Insufficiency of cervical anastomosis was seen in 16 (13.4%), paresis
      of recurrent nerve--in 4 (3.4%) patients. Hospital lethality was 3.4% (4
      patients). Good and satisfactory long-term results of esophagoplasty were
      achieved in 97 (97.0%) patients. PEBS is the indication for transhiatal
      extirpation of the esophagus with its one-stage plastic repair with gastric tube
      (or large intestine) during first 6 months after burn.

PMID- 12001676
TI  - [Surgical treatment of endocrine-cell tumors of hepato-pancreatic-duodenal zone
      (comment of the editor)].
AB  - Endocrine-cell tumors of hepatopancreatoduodenal zone are rare diseases. Their
      rate doesn't exceed 1-4% of all tumors of this location. 79 patients with
      endocrine-cell tumors of hepatopancreatoduodenal zone were treated, 67 of them
      underwent surgical treatment (operability was 67.1%) Radical operations were
      performed in 45 patients (gastropancreatoduodenal resection--17, distal resection
      of the pancreas--16, tumor enucleation--5, hemihepatectomy--3, liver resection-
      4). Prognosis of endocrine-cell tumors of hepatopancreatoduodenal zone is
      relatively favorable. In radically operated patients the presence of metastases
      to lymph nodes doesn't influence long-term results which are better than ones of
      chemo- or radiotherapy. Correlation between long-term results of surgery and age
      of patients, tumor sizes and its histologic structure was not revealed.
      Radicality of surgery is the only factor influencing prognosis. It is necessary
      to expand indications for extended operations, and to perform multi-stage
      operations in some cases of recurrences.

PMID- 12001677
TI  - [Cryoplasma-anti-enzyme combination in the treatment of acute pancreatitis].
AB  - Results of treatment of 397 patients with acute pancreatitis are analyzed. Use of
      fresh-frozen and cryosupernatant plasma, heparin and protease inhibitors provide
      more effective elimination of disseminated intravascular blood coagulation
      syndrome, disorders of microcirculation that permits to improve results of
      treatment.

PMID- 12001678
TI  - [Technical appliances for the Segal retractor in abdominal surgery].
AB  - Additional specula and other technical appliances for Sigal retractor (patent No.
      2147840 of 27.04.2000) were used in 300 operations. These appliances make easier
      surgical approach, in particular dislocation not only of surgical wound margins
      but also of lower tissues (visceral organs--urinary bladder, uterus, liver, etc).
      It prevents intraoperative complications, increases ablation of surgery, reduces
      surgical team.

PMID- 12001679
TI  - [Minimally invasive and organ-saving operations in abdominal trauma].
AB  - Results of surgical treatment with modern minimally invasive methods of 968
      patients with isolated and combined abdominal trauma were analyzed. These methods
      permitted to make topic diagnosis earlier and to perform adequate surgery on
      injured organs in 82.0% patients, including in 34.0% with endoscopic-assisted
      operations, in 36.0% patients diagnostic laparotomies were avoided. In spleen
      trauma organ-saving and replacement operations were performed for prophylaxis of
      postsplenectomy syndrome. Vagodestruction of the stomach and pancreas with
      electromagnetic waves was successfully used in 32 patients for prophylaxis of
      traumatic pancreatitis and gastrointestinal ulcers. Minimally invasive
      technologies and organ-saving operations permitted to reduce intra- and
      postoperative complications rate from 29.7 to 16.8%, lethality--from 12.3 to
      7.4%.

PMID- 12001680
TI  - [Suturing techniques for laparotomy wounds].
AB  - The author proposes a new method of suturing laparotomy wounds--extrafocal
      connection of wound margins with adaptive-repositive devices which permit to
      minimize damage and microcirculatory disorders of sutured tissues, and to reduce
      purulent complications rate from 30.6 to 11% (2.8 times) compared with routine
      method of tissues connection. The proposed method is recommended for patients
      with high risk of pyoinflammatory complications.

PMID- 12001681
TI  - [The diagnosis and treatment of cholangiolithiasis after cholecystectomy].
AB  - Results of complex examination and treatment of 138 patients with
      postcholecystectomic cholangiolithiasis were analyzed. Residual
      cholangiolithiasis was diagnosed in 104 (75.4%), recurrent--in 34 (24.6%)
      patients. Differential-diagnostic symptoms of residual and recurrent
      cholangiolithiasis are specifiEd. Diagnostic and curative algorithm was
      developed, criteria of choice of curative (instrumental or surgical) methods were
      clarified. Mini-invasive surgeries (endoscopic papillosphincterotomy,
      suprapapillar choledochoduodenostomy, dissection of stenosed
      choledochoduodenoanastomosis, percutaneous transhepatic cholangiostomy,
      lithoextraction through external bile fistual, mechanical and laser lithotripsy,
      nasobiliar drainage) from different diapeutic approaches were performed in 137
      (99.3%) patients. Diapeutic instrumental procedures were effective and final in
      91.9% cases (in residual cholangiolithiasis--94.2%, in recurrent--82.4% cases).
      Lethality was 0.7%.

PMID- 12001682
TI  - [Treatment of complications of pylorus preserving stomach resection].
AB  - Causes of unsatisfactory outcomes of pylorus preserving stomach resection are
      analyzed, method of prophylaxis and surgical correction is proposed. Pylorus
      preserving stomach resection was performed in 207 patients with chronic gastric
      ulcer. 2 groups of patients were compared: 166 patients who have undergone
      pylorus preserving stomach resection by Maky--Gorobashko (group 1); 41 patients
      operated according to an original method of suprapyloric stomach resection with
      preserving of distal Latarget nerves on serous-muscular flap formed from lesser
      curvature of the stomach (group 2). Of 122 examined patients of group 1 excellent
      and good long-term results according to Visick's criteria were achieved in 101
      (82.79%), satisfactory--in 12 (9.84%), unsatisfactory--in 9 (7.37%). Bad stump
      evacuation due to a stable spasm of the denervated pylorus and hypokinesia of the
      stump were the main causes of unsatisfactory results. In group 2-39 of 41
      patients were examined in long-term period. Excellent and good results were
      achieved in 38 patients, satisfactory--in 1. There were no unsatisfactory
      results.

PMID- 12001683
TI  - [Prophylaxis of esophageal reflux after gastrectomy and proximal stomach
      resection].
AB  - 498 operations are analyzed. Simplified invagination with shuttle suture is the
      advantage of proposed method. Postoperative complications were seen in 18.3%
      patients, lethality was 3.6%. Mild reflux-esophagitis was revealed in 8 (4.9%) of
      162 examined patients, cicatricial stricture of I-II degree--in 19 (11.7%)
      patients. The proposed esophageal-gastric and esophageal-intestinal invagination
      anastomoses are easy, to make, safe, have high antireflux effect. This
      modification of invagination anastomoses is recommended in proximal stomach
      resection and gastrectomy.

PMID- 12001684
TI  - [Rehabilitation of patients after suturing perforated duodenal ulcer].
AB  - 516 patients with perforated duodenal ulcer were operated, 396 of them underwent
      palliative operations. Long-term results were studied in 237 patients.
      Determination of individual sensitivity to H2-blockers of histamine receptors
      with 24 hour pH-metry demonstrated tendency towards reduction of therapeutic
      effect time, and in 17-18% cases--resistance development. Individual selection of
      drugs with diet, obligative antihelicobacter therapy with eradication control
      permit to reduce ulcer recurrence rate from 65.5 to 4.8%. Success depends on
      organisation of rehabilitation and prophylactic treatment.

PMID- 12001685
TI  - [Classification and principles of treatment of acute purulent peritonitis].
AB  - State of immune-secretory system of intestinal mucosa, bacterial contamination of
      the small intestine, peritoneal exudate, portal and systemic venous blood,
      ultrastructural changes in the liver (electron microscopy) were studied in 167
      patients with general acute purulent peritonitis (APP) and clinical-laboratory
      symptoms of endotoxicosis. It is demonstrated that the main links of APP
      pathogenesis are disorders of small intestine barrier function, massive bacterial
      translocation from intestinal lumen to abdominal cavity and portal circulation,
      damage of reticuloendothelial hepatic barrier manifested as fulminant macrophagal
      hepatic failure, "bursting" of infectious-toxic agents into systemic circulation
      with resultant toxico-septic shock and visceral insufficiency. This approach
      permits to classify three clinical stages of APP and to propose differential
      surgical policy and detoxication treatment for these patients.

PMID- 12001686
TI  - [Intestinal obstruction due to cholelithiasis].
AB  - Medical histories of 22 patients operated for obturative intestinal obstruction
      due to cholelithiasis were analyzed, some specific features of this disease were
      defined. Surgical treatment consisted of enterotomy and cholelithoextraction with
      obligative decompression of higher intestinal parts. Sound stimulation of the
      intestine by Russian apparatus "Aropak-536" in combined treatment permitted to
      restore earlier motor function of gastrointestinal tract.

PMID- 12001687
TI  - [Ultrasonic diagnosis of lung echinococcosis in children].
AB  - Echography was used for diagnosis of pulmonary hydatid cysts in 62 patients aged
      from 2 to 14 years. Ultrasonic examination was carried out after detection of
      focal image on chest survey roentgenogram. A hydatid cyst of lung's inferior lobe
      was diagnosed occasionally during abdominal echography due to abdominal pains in
      8 (12.9%) children. Echographic picture of pulmonary hydatid cysts was different
      depending on Echinococcus stage, presence of complications (cyst suppuration,
      drainage into bronchial tree). Echography clearly shows location, shape,
      contours, sizes, internal structure of cysts, width of dehiscence of pleural
      layers in reactive pleurisy, state of adjacent pulmonary tissue. US-diagnosis is
      most valuable after surgery for monitoring of cyst bed state, volume of pleural
      exudate, possible complications.

PMID- 12001688
TI  - [Prolene Hernia System for hiatal hernia-plasty].

PMID- 12001689
TI  - [Antibacterial and immunocorrective therapy in the complex of curative measures
      for acute peritonitis].

PMID- 12001690
TI  - [Prosthesis of thoraco-abdominal aorta according to the method of distal
      "elephant trunk" with simultaneous aortocoronary bypass under deep hypothermia
      and circulatory arrest].

PMID- 12001691
TI  - [Life-term diagnosis and treatment of malignant vipoma of the pancreas].

PMID- 12001692
TI  - [Acute dilatation of the stomach in a patient after appendectomy].

PMID- 12001693
TI  - [Ultrasound for diagnosis and treatment of surgical diseases of the lungs and
      pleura].

PMID- 12001694
TI  - Management of the brain-dead, heart-beating potential donor.

PMID- 12001695
TI  - Increased expression of matrix metalloproteinase-2: a diagnostic marker but not
      prognostic marker of papillary thyroid carcinoma.
AB  - BACKGROUND: Matrix metalloproteinases are proteolytic enzymes that degrade
      extracellular matrix components. Numerous studies have demonstrated that
      individual MMPs play a crucial role in tumor invasion and metastasis. OBJECTIVE:
      To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and
      normal thyroid tissues. METHODS: We examined 33 cases of thyroid tumor
      (papillary, follicular and medullary carcinoma, follicular adenoma and
      multinodular goiter). MMP protein content and activity were measured by enzyme
      linked immunosorbent assay and gel zymography. Immunohistochemistry was also
      performed. RESULTS: The thyroid tissues examined secreted MMP-2 and 9 as well as
      TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases
      compared to the adjacent normal tissue or to the other tumor entities. Increased
      MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary
      epithelial component. No significant difference was seen between papillary
      carcinomas with lymph node metastases and those without. CONCLUSIONS: Increased
      MMP-2 expression may be useful as a diagnostic marker to differentiate papillary
      carcinoma from other thyroid neoplasms, but it cannot serve as a useful
      prognostic marker.

PMID- 12001696
TI  - Deliberate self-poisoning in adolescents.
AB  - BACKGROUND: Adolescent suicide has become increasingly more prevalent in recent
      years, with self-poisoning being a frequent means of suicide attempt. OBJECTIVE:
      To investigate the factors associated with adolescent self-poisoning. METHODS:
      Data on adolescents referred for intentional self-poisoning to the Adolescent
      Medical Unit during the years 1990-1998 were evaluated retrospectively. Data were
      obtained from the hospital medical records and included the following factors:
      sociodemographic data, educational status, agent and route of intake, motivation
      for overdose, and the extent of serious suicidal intent. RESULTS: We evaluated
      324 cases of adolescent self-poisoners aged 12-18 years (mean +/- SD 14.8 +/- 1.5
      years). The female/male ratio was 8:1. Most of the patients were attending school
      and lived in urban areas. Oral ingestion was the only route of intake; 84.5% of
      the patients ingested drugs and 10.5% non-medicinal compounds. The drug most
      commonly taken was acetaminophen. The non-medicinal compounds were mostly
      pesticides and household materials. The suicide attempts were most frequently
      associated with transient depression, stemming from defects in child-family
      communication. As based on clinical psychiatric evaluation, patients who had
      ingested polydrugs and non-medical compounds evidenced a significantly greater
      suicidal intent (chi 2 = 11.9, P < 0.001) compared to those who took only one or
      two kinds of drugs. CONCLUSIONS: We found that self-poisoning attempts occur most
      frequently in depressed females at junior high and high school, usually in the
      context of family dysfunction. Non-medicinal agents and polydrug ingestion are
      major risk factors for evaluating the seriousness of the suicidal intent.

PMID- 12001697
TI  - Continuous intravenous epoprostenol in pulmonary hypertension: the Israel
      experience.
AB  - BACKGROUND: Primary idiopathic pulmonary hypertension is a rapidly progressive
      disease with a median survival of less than 3 years. Recently its prognosis was
      shown to dramatically improve with the use of epoprostenol, an arachidonic acid
      metabolite produced by the vascular endothelium, which increases the cardiac
      output and decreases the pulmonary vascular resistance and pulmonary arterial
      pressure. This drug enhances the quality of life, increases survival and delays
      or eliminates the need for transplantation. OBJECTIVE: To review the experience
      of Israel hospitals with the use of epoprostenol. METHODS: The study group
      comprised 13 patients, 5 men and 8 women, with an age range of 3-53 years. All
      patients suffered from arterial pulmonary hypertension. Epoprostenol was
      administered through a central line in an increased dose during the first 3
      months, after which the dose was adjusted according to the clinical syndrome and
      the hemodynamic parameters. RESULTS: After 3 months the mean dose was 10
      ng/kg/min and the pulmonary artery pressure decreased from 7 to 38%. After one
      year, the PAP decreased at a slower rate. Two cases required transplantation,
      three patients died, and seven continued taking the drug (one of whom
      discontinued). Four episodes of septicemia were observed. Today 10 patients are
      alive and well and 7 continue to take epoprostenol. CONCLUSION: We found that
      epoprostenol improves survival, quality of life and hemodynamic parameters, with
      minimum side effects.

PMID- 12001698
TI  - The "Sheba" model of comprehensive orthogeriatric care for elderly hip fracture
      patients: a preliminary report.
AB  - BACKGROUND: The progressive increase in the number of elderly patients with hip
      fractures and the particular multidisciplinary needs of this population call for
      the investigation of other models of orthogeriatric care. OBJECTIVES: To describe
      the nature and assess the feasibility of a comprehensive orthogeriatric unit
      attending to patients' surgical, medical and rehabilitation needs in a single
      setting. METHODS: This retrospective chart review describes consecutive older
      patients with hip fractures admitted directly from the emergency ward to an
      orthogeriatric ward. RESULTS: The mean age of the 116 patients evaluated was 82.4
      years. Delay to surgery was 3.6 +/- 3.1 days and total length of stay 23.9 +/-
      11.0 days. No patient was transferred to other acute medical wards of the
      hospital and 66.4% were able to return to their previous living place. Rates of
      major complications and mortality were extremely low. CONCLUSION: The present
      model of a comprehensive orthogeriatric ward is a practical, applicable and
      feasible service for elderly hip fracture patients and can cover the various
      needs of these patients. The deployment arrangements needed to establish and
      operate the ward were minimal and there were only a few management and
      organizational problems. The cost-effectiveness and other comparative benefits of
      this type of service have yet to be clarified.

PMID- 12001699
TI  - Acquired neurogenic abdominal wall weakness simulating abdominal hernia.

PMID- 12001700
TI  - The clinical manifestations of lithium intoxication.
AB  - BACKGROUND: Lithium has been a part of the psychiatric pharmacopoeia for more
      than half a century. Its efficacy is marred by a narrow therapeutic index and
      significant toxicity. OBJECTIVES: To increase physicians' awareness of the
      various manifestations of lithium intoxication. METHODS: We reviewed the clinical
      data of cases of lithium poisoning occurring in a municipal hospital during a 10
      year period. RESULTS: Eight patient records were located. The mortality rate was
      12.5%. All patients were women and the mean age was 66.4 years. The most common
      symptoms were neurologic. One illustrative case is described in detail with
      lithium serum levels showing the usual two-phase decline. CONCLUSIONS: Lithium
      poisoning can present in many forms. Increased physician awareness and the early
      use of effective treatment, mainly hemodialysis, will prevent mortality and
      protracted morbidity associated with this condition.

PMID- 12001701
TI  - Developments in hematopoietic stem-cell transplantation in the treatment of
      autoimmune diseases.
AB  - Intractable forms of autoimmune diseases follow a rapid course, with a
      significantly shortened life expectancy sometimes comparable to that of malignant
      diseases. Immunoablative therapy, including high dose cytotoxic agents and
      hematopoietic autologous stem-cell rescue, was recently introduced as an
      aggressive approach to treat autoimmune diseases that have a rapid course and are
      resistant to conventional therapy. The most frequent indication for this type of
      treatment is multiple sclerosis, seconded by systemic sclerosis. The results of
      immunoablative treatment with documented responses in both diseases are
      encouraging. The data are mature enough to begin comparative randomized studies
      of immunoablative versus conventional treatment to validate the benefit of the
      aggressive approach. A randomized trial involving SSc was recently launched
      (ASTIS) and a trial involving MS is in preparation. Considerably less experience
      with immunoablative treatment has been gained in systemic lupus erythematosus,
      rheumatoid arthritis, and other disorders with an autoimmune pathophysiology.
      Autologous hematopoietic stem cell transplantation in humans offers more long
      lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic
      transplantation may replace the whole immune system. However, this attractive
      approach is still associated with considerable morbidity and mortality and is not
      yet justified for treatment of autoimmune diseases. Non-myeloablative allogeneic
      transplantation and sub-myeloblative high dose cyclophosphamide without stem cell
      support are alternative approaches that could be explored in pilot studies.

PMID- 12001702
TI  - Non-myeloablative stem-cell transplantation in the treatment of malignant and non
      malignant disorders.

PMID- 12001703
TI  - Matrix metalloproteinases: promoters of tumor progression and invasiveness.

PMID- 12001704
TI  - Adolescent suicide and attempted suicide.

PMID- 12001705
TI  - Non-myeloblative stem-cell transplantation for immunotherapy of cancer and non
      malignant diseases with allogeneic lymphocytes.

PMID- 12001706
TI  - Novel aspects of hypogammaglobulinemic states: subcutaneous immunoglobulin
      treatment.

PMID- 12001707
TI  - Mechanical alternatives to the human heart: future devices.

PMID- 12001708
TI  - Novel aspects of hypogammaglobulinemic states.

PMID- 12001709
TI  - Massive thyroid hormone overdose: kinetics, clinical manifestations and
      management.

PMID- 12001710
TI  - Sensorineural hearing loss and metastatic leptomeningeal malignancy.

PMID- 12001711
TI  - Streptococcal septic arthritis and necrotizing fasciitis in an intravenous drug
      user couple sharing needles.

PMID- 12001712
TI  - Perforated peptic ulcer masquerading as gallbladder disease: CT findings.

PMID- 12001713
TI  - Severe pharyngeal stenosis after caustic ingestion.

PMID- 12001714
TI  - The provision of modern medical services to a nomadic population: a review of
      medical services to the Bedouins of southern Sinai during Israeli rule 1967-1982.
AB  - Southern Sinai, a mountainous desolated arid area, is inhabited by Bedouin nomad
      tribes composed of Arabic-speaking Moslems. Until the Six Day War between Egypt
      and Israel in 1967, healthcare services in the region were based on traditional
      medicine performed by the Darvish, a local healer. Over the course of Israeli
      rule (1967-1982) an elaborate healthcare service was established and maintained,
      providing modern, up to date, comprehensive medical services that were available
      to all free of charge.

PMID- 12001715
TI  - The Second International Conference on the Neuroendocrine Immune Basis of the
      Rheumatic Diseases.

PMID- 12001716
TI  - Defining alternative medicine.

PMID- 12001717
TI  - Unusual cluster of parvovirus arthritis.

PMID- 12001718
TI  - Pseudoascites.

PMID- 12001719
TI  - Primary antiphospholipid syndrome as the cause of renal artery thrombosis.

PMID- 12001720
TI  - Changes in air humidity and the incidence of acute laryngotracheitis.

PMID- 12001721
TI  - Candle wax as ocular foreign body.

PMID- 12001722
TI  - [Actions of neuroactive steroids in neurons].
AB  - The term "neuroactive steroids" applies to those steroids that have biological
      activities in nervous system. These neuroactive steroids can be divided into
      three categories according to the mechanism of their effects: (1) Effects
      mediated by membrane receptors including GABAA receptor and NMDA receptor that
      are ion channels; (2) Effects mediated by membrane receptors that are coupled
      with second messenger systems; (3) Effects mediated by intracellular receptors
      which in turn modulate gene expression. These neuronal effects of steroids,
      especially modulation of the ion-channel receptor and G protein--coupled
      receptor, have drawn more attention of the researchers.

PMID- 12001723
TI  - [Progress of monoaminergic receptor investigation on depression].
AB  - It is widely accepted that monoamine transmitters are playing an important role
      in the progress of depression. The functions of monoamine transmitters and their
      receptors change profoundly during depression and its treatment. This paper is
      attempted to review the new progress of investigation into serotonin receptors,
      adrenoceptors and dopamine receptors related with depression mechanism
      respectively.

PMID- 12001724
TI  - [Voltage-gated potassium channels and human neurological diseases].
AB  - Voltage-gated potassium channels (Kv) is the largest, most complex in potassium
      channel superfamily. It can be divided into Kv alpha subunit and auxiliary two
      groups. The roles of some Kv channels types, e.g. rapidly inactivating (A-Type
      channel) and muscarine sensitive channels (M-type channel) are beginning to be
      understood. They are prominent in nervous system, acting in delicate and accurate
      ways to control or modify many physiological and pathological functions including
      membrane excitability, neurotransmitter release, cell proliferation or
      degeneration, signal transduction in neuronal network. Many human neurological
      disease pathogenesis are found to be related to mutant of Kv-channels subunit or
      subtype, such as, learning and memory impairing, ataxia, epilepsy, deafness, etc.

PMID- 12001725
TI  - [The research into functions of heme oxygenase system in brain].
AB  - Heme oxygenase(HO) is a microsomal enzyme involved in the degradation of heme,
      resulting in the generation of biliverdin, iron, and carbon monoxide. Two HO
      isoenzymes, HO-1 and HO-2, have been found to distribute widely in brain with
      different mechanism of regulation. Both of them may play important roles in
      modulating intracellular NO, balancing antioxidative/oxidative stress, and
      accelerating neurodegeneration.

PMID- 12001726
TI  - [My odyssey in engaging in physiology].

PMID- 12001727
TI  - [Involvement of immune system in the pathogenesis of viral myocarditis].
AB  - Myocarditis is thought to be commonly caused by various viruses, and accumulating
      evidence links viral myocarditis with the eventual development of dilated
      cardiomyopathy. Heart disease is the most prevalent cause of morbidity and
      mortality in developed countries. Cytokines are being increasingly recognized as
      an important factor in the pathogenesis of myocarditis and cardiomyopathy.
      Elevated levels of circulating cytokines have been reported in patients with
      heart failure, and various cytokines have been shown to depress myocardial
      contractility in vitro and in vivo. A number of reports have shown that cytokines
      generated by activated immune cells cause an increase in nitric oxide (NO) via
      induction of NO synthase. Increased generation of NO may induce myocardial
      damage. It has been suggested that NO can be either beneficial or harmful to the
      host, NO can protect the myocardium against damage from CVB3 infection by
      inhibiting viral replication. A better molecular understanding of the direct
      effect of viral infection on cardiac myocytes and the balance of beneficial and
      detrimental effects of the immune response will ultimately provide insight into
      the mechanisms by which viral infections cause cardiomyopathy in humans.

PMID- 12001728
TI  - [Therapeutic potential of the neural stem cells against ischemic brain injury].

PMID- 12001729
TI  - [The effects of IL-1 beta on ischemia-induced brain damage].

PMID- 12001730
TI  - [Roles of polo like kinases (plks) in cell division].

PMID- 12001731
TI  - [A newly found regulation peptide ghrelin].

PMID- 12001732
TI  - [The mechanism about nutrients regulation of gene expression in animal].

PMID- 12001733
TI  - [Progress in the study of quercetin metabolism].

PMID- 12001734
TI  - [Regulation of prostatic growth and function by polypeptide growth factors].

PMID- 12001735
TI  - [Current situation of peptide nucleic acid research and development].

PMID- 12001736
TI  - [Human body odors and their function].

PMID- 12001737
TI  - [Biomarkers of aging].

PMID- 12001738
TI  - [Research progress in cardiovascular effects of phytoestrogen].

PMID- 12001739
TI  - [Trends in the post-genomic pharmacological research].
AB  - With the advent of post-genome era, pharmacogenomics will be a new field in
      pharmacological sciences. In parallel, high-throughput screening, in silico
      research, as well as lots of visualization techniques are emerging as novel
      approaches in pharmacological researches. Some progress in the implementation of
      aforementioned new idea and methods in pharmacodynamics and pharmacokinetics
      research are also introduced in this review.

PMID- 12001740
TI  - [The advances on biologic function of astrocytes].

PMID- 12001741
TI  - [Thioredoxin and neurodegenerative diseases].

PMID- 12001742
TI  - [The function and regulation mechanism of the cardiovascular areas in the caudal
      ventrolateral medulla].

PMID- 12001743
TI  - [Glia mediate gonadal hormone action on the nervous system].

PMID- 12001744
TI  - [Apoptosis in mammalian reproduction].

PMID- 12001745
TI  - Viral hemorrhagic fevers.

PMID- 12001746
TI  - Efficacy of raloxifene for treatment of menopause: a systematic review.
AB  - PURPOSE: To critically appraise recent randomized controlled trials (RCT) of
      raloxifene and its effects on the long-term consequences of menopause. DATA
      SOURCES: All RCTs of greater than six months duration in post-menopausal women
      found in MEDLINE through July 2000. CONCLUSIONS: Raloxifene lowered lipids, but
      estrogen had a more beneficial effect on HDL and fibrinolytic markers. Raloxifene
      had a more beneficial effect on triglycerides, inflammatory and thrombogenic
      markers. Compared to placebo, raloxifene reduced vertebral fractures but had a
      similar although lesser effect on bone mineral density and markers of bone
      turnover than estrogen. Estrogen receptor positive breast cancer was reduced by
      90% with no increase in the incidence of endometrial cancer with raloxifene. The
      most serious side effect of raloxifene was an increased incidence of deep vein
      thromboses and pulmonary emboli. IMPLICATIONS: Raloxifene has been shown to be
      beneficial using cardiovascular and osteoporosis end-points in studies of short
      duration. More RCTs of longer duration with comparisons to other traditional
      treatments are needed before raloxifene becomes the treatment of choice.

PMID- 12001747
TI  - Addressing use of herbal medicine in the primary care setting.
AB  - PURPOSE: To critically evaluate existing approaches to the integration of
      allopathic and complementary and alternative medicine (CAM) and develop a middle
      ground approach to addressing use of herbal medicine and other forms of CAM in
      the primary care setting. DATA SOURCES: Extensive review of scientific literature
      and Internet sources supported by legal, philosophical, and ethical arguments.
      CONCLUSIONS: A review of medical literature indicates that a growing number of
      people perceive both allopathic and CAM to be valued aspects of health care.
      Whether we agree with this perception or not, ethical, legal, clinical, and
      social considerations dictate that we assist patients in their efforts to derive
      benefit from use of CAM while helping them to minimize risks. Yet the current
      approach to addressing CAM in primary care is "don't ask, don't tell," with
      approaches to filling this clinical void ranging from "just say no" to CAM use,
      to allopathic practitioners who also are CAM practitioners. IMPLICATIONS FOR
      PRACTICE: It is possible to occupy the middle ground, neither rejecting nor
      embracing CAM, but recognizing its significant impact on health care. In order to
      do this safely, clinicians need to be informed about herbs and other CAM
      practices, document thoroughly the informed consent and decision-making process,
      and monitor patients carefully for adverse effects.

PMID- 12001748
TI  - Promoting health among perimenopausal women through diet and exercise.
AB  - PURPOSE: To review the literature related to health promotion during the
      perimenopausal years and suggest methods for integrating those changes into the
      lifestyles of women in primary care. DATA SOURCES: Selected scientific literature
      and guidelines for exercise programs. CONCLUSIONS: The transition into
      perimenopause presents an opportunity for addressing health promotion issues,
      such as diet and exercise. As a woman senses perimenopausal changes, health
      awareness emerges. Such personal insight motivates the woman to implement
      lifestyle changes. IMPLICATIONS FOR PRACTICE: Considering the average women will
      spend approximately one third of her life past menopause, a concerted effort is
      needed to ensure her well-being. Diet and exercise represent two modifiable areas
      of concern for perimenopausal women. Dietary selections of phytoestrogens,
      calcium, fiber and fat along with exercises plans are relatively simple
      interventions to begin the process of change.

PMID- 12001749
TI  - A profile of nurse practitioners in emergency care settings.
AB  - PURPOSE: To determine characteristics of nurse practitioners (NPs) who provide
      emergency care. DATA SOURCES: Descriptive cross-sectional study of a convenience
      sample of 113 NPs in emergency care obtained from the online Resource Directory
      of Nurse Practitioners in Emergency Care. CONCLUSIONS: The majority of NPs in
      emergency care worked in facilities that were located in urban/suburban areas,
      were responsible for providing care in both the main emergency department and
      fast track area, held a Master of Science degree in nursing, obtained their
      education as a family nurse practitioner, and were certified as an NP by a
      national certifying agency. They were experienced registered nurses before
      becoming an NP but were relatively new to the NP role. IMPLICATIONS: The results
      of this study provide information about characteristics of NPs who provide
      emergency care.

PMID- 12001750
TI  - Utilization and scope of practice of Nurse Practitioners and physician assistants
      in Montana.
AB  - PURPOSE: To explore the licensing, certification, governance and education
      requirements of nurse practitioners (NPs) and physician assistants (PAs) in the
      state of Montana. Services provided and privileges retained in employment were
      also analyzed. DATA SOURCES: This was a descriptive study using a survey of rural
      hospital administrators (N = 34). CONCLUSIONS: Survey results show that 92.5% of
      PAs in Montana meet their supervision requirement by a telephone contact
      provision outlined by the state board of medicine. In contrast, 54.2% of NPs, who
      are autonomous by legal definition, have a telephone supervision requirement
      imposed on them by their employers. IMPLICATIONS FOR PRACTICE: These findings
      have implications for the current and prospective professionals and the
      businesses for which they work. Nurse practitioners and their professional
      organizations need to consider the implications these findings have on the
      professional image and marketability of all NPs.

PMID- 12001751
TI  - Professional hospital librarians--doing better what we've always done well.

PMID- 12001752
TI  - CHI services: Planetree--a patient-centered care concept.

PMID- 12001753
TI  - OPL. Factors affecting OPL performance.
AB  - Case study. The CEO of a mid-size community hospital requested a literature
      search on the standards, costs and regional competition for a pain management
      center. Results submitted were deemed less than satisfactory. A review of the
      case suggests numerous elements, listed below, which need to be addressed and
      revised in order to improve outcome in future interactions.

PMID- 12001754
TI  - Happy anniversary! Consortium for Health Information & Library Services. 1976
      2001.

PMID- 12001755
TI  - [Human delivery and it's individualistic schedule in the XXI century].

PMID- 12001756
TI  - [Imbalance of pro-oxidants-antioxidants in blood of pregnant women with pregnancy
      induced hypertension].
AB  - DESIGN: The purpose of our study was to determine a prooxidant-antioxidant
      balance in pregnant women with the newly diagnosed pregnancy-induced hypertension
      and in normal pregnancies. MATERIALS AND METHODS: The research was performed on
      20 pregnancies complicated with hypertension (PIH) and 17 normal pregnancies in
      the third trimester of gestation. The age, BPs, BPd, edema and proteinuria were
      noted to characterize the patients. The reduced glutathione concentration and the
      glutathione peroxidase activity were measured in red blood cell hemolysates. In
      plasma, the concentrations of the thiobarbituric acid reactive substances such as
      lipid peroxidation products and the hydrogen peroxide were determined. RESULTS:
      There were patients of similar age: pregnancies with PIH and uncomplicated
      pregnancies were 25.7 +/- 3.96 years old and 25.7 +/- 4.54 years old,
      respectively. Proteinuria was found in five pregnancies with PIH and in one
      normal pregnant woman. Edema was noted in eight pregnancies with PIH and in three
      normal pregnancies. In the group of pregnancies complicated with hypertension,
      BPs and BPd were 147.7 +/- 6.78 mmHg and 94.2 +/- 4.94 mmHg, respectively. In the
      group of patients with PIH, reduced glutathione concentration significantly
      decreased and the TBARS levels increased as compared with results noted in normal
      pregnancies. No differences in the glutathione peroxidase activity and the
      hydrogen peroxide concentration were noted between groups of patients.
      CONCLUSIONS: Obtained results of the research allowed us to conclude that the
      pregnancy-induced hypertension is associated with the overproduction of lipid
      peroxides and impaired antioxidant defence.

PMID- 12001757
TI  - [Use of oxi-cardiotocography in twin delivery].
AB  - The intrapartum management of multiple gestation continues to challenge the
      obstetrics profession. Electronic fetal heart rate monitoring and fetal pulse
      oximetry are used in clinical research to assess fetal well-being during labor.
      The objective of this study was to establish values of fetal arterial oxygen
      saturation (FSpO2) and some other parameters by dint of computerised analysis of
      cardiotocogram during twin delivery. 5 cases of vaginal twin deliveries as the
      Clinic of Perinatology of the Institute of Gynecology and Obstetrics Lodz Mecical
      University over the years 1988-1999 were reviewed. In four cases vertex-vertex
      twins were delivered vaginally, while in one case an assisted breech extraction
      was conducted on vertex-non vertex twins. The foetus was monitored continually
      with a Oxford S 8000 systems and pulse oximeter Nellcor N-400. the medium
      parameters of computerised analysis of CTG and FSpO2 during progressive stages of
      labour were shown. Twin delivery needs modern fetal monitoring tools to provide
      the obstetrician information on well-being of the foetus. It is possible to
      monitor fetal oxygen saturation and CTG parameters in both of the twins during
      labour The ability to measure fetal oxygen saturation especially during the
      second stage of twin labor adds critical information about fetal status and
      refines the interpretation of abnormal FHR patterns. Only after examining a large
      number of twin fetuses we can assess whether pulse oximetry in useful in
      management of labor.

PMID- 12001758
TI  - [Results of treating stage IB invasive carcinoma of the cervix complicating
      pregnancy].
AB  - The results of radical surgery in 18 patients with stage IB invasive carcinoma of
      the cervix with concurrent pregnancy are presented. All patients were treated
      with radical Wertheim-Meigs hysterectomy with ovarian preservation. In four cases
      the treatment was delayed to meet patients will and achieve fetal maturity. There
      was no significant difference in the expected five-year survival of analyzed
      population (5 yrs survival of 83%) and control group consisting of 32 patients
      with stage IB carcinoma of the cervix without accompanying pregnancy treated in
      the same method and the same time. All patients with planned delay in therapy
      were cured.

PMID- 12001759
TI  - [Proposal for delivery in the XXI century].

PMID- 12001760
TI  - [Stage IIb invasive carcinoma of the cervix during pregnancy--personal experience
      and contemporary opinions on this topic].
AB  - Five cases of the cervical cancer in stage II b coexisting with pregnancy were
      presented. All patients were treated by radical radiotherapy consisting of
      external beam irradiation and brachytherapy. The spontaneous abortion or
      premature labor occurred during radiation after the dose 30.6-32 Gy of
      irradiation was delivered. In two cases where cervical carcinoma was diagnosed
      during the III trimester, cesarean section were performed between 34 and 36 weeks
      of gestation. Two healthy babies were delivered. Only in one case the recurrence
      occurred and that woman died 43 months after the initial diagnosis.
      Individualization of the treatment in such cases should be considered. It is
      necessary to establish centers which could be experienced in the treatment of
      pregnant women suffering from cervical cancer.

PMID- 12001761
TI  - [Evaluation of antiepileptic therapy during pregnancy].
AB  - OBJECTIVE: The aim of the study was to analyse the course of pregnancy and labour
      in women with epilepsy. MATERIAL AND METHODS: The study was carried out on 53
      pregnant women with epilepsy who delivered in the Department of Obstetrics and
      Perinatology of the University School of Medicine in Lublin (group E). RESULTS:
      In the group of women with epilepsy there were observed more pregnancy
      complications. The mean birth weight of infants and the condition of the infant
      after birth evaluated were lower in the study group E according to Apgar score.
      The increased risk of congenital malformations and intrauterine foetal growth
      retardation were observed in children exposed to valproate or carbamazepine in
      monotherapy or combination of phenobarbital and phenytoin and the combination of
      phenobarbital, phenytoin and primidone in polytherapy. CONCLUSION: Women with
      epilepsy require appropriate pregnancy planning and appropriate neurologic and
      obstetric care preconceptionally and during pregnancy.

PMID- 12001762
TI  - [Evaluation of transplacental gradient for cadmium and lead].
AB  - The aim of the study was to determine the concentration of lead and cadmium in
      blood of 83 pregnant women from Szczecin and in umbilical cord blood of their
      newborns. Mean concentration of lead in women was 2.56 micrograms/dl and in
      umbilical cord blood was 2.01 micrograms/dl. The mean concentration of cadmium in
      women was 0.056 microgram/dl and umbilical cord blood was 0.21 microgram/dl. A
      positive correlation was noted between lead concentration in maternal and
      umbilical cord blood (r = 0.59). The similar correlation between cadmium
      concentration in maternal blood and umbilical cord blood was observed. The
      transplacental gradient for lead was 78.52%, and for cadmium--37.5% respectively.

PMID- 12001763
TI  - [Ureter injury as a gynecologic surgery complication--prospects for conservative
      treatment].
AB  - There we presented three cases of ureteral injury after gynecological operations.
      In two cases partial ureteral obstruction was treated by creating percutaneous
      renal fistula. In the latter case, in spite of conservative treatment (double J
      catheter), a uretero-vaginal fistula was detected.

PMID- 12001764
TI  - [Congenital absence of the vagina--its diagnostic-therapeutic implications--case
      report].
AB  - Issues relating to diagnosis and reconstructive therapy for developmental
      anomalies of female genital tract are controversial. The teratogenic influence
      during the 6th week of intrauterine life, the time for the development of
      structures such as fallopian tube, uterus and cervix from the Mullerian duct may
      lead to their defective formation. In a 14 year old girl congenital absence of
      vagina, cervix developed right half of uterus (rudimentary horn?) and a pelvic
      kidney was diagnosed by laparoscopy and laparotomy. The attempt to connect uterus
      with the artificial vagina during the laparotomy was unfortunately not
      successful, the main reason being prolonged distance between the apex of
      artificial passage and the rudimentary uterus. In our opinion ultrasound is a
      superior diagnostic tool for diagnosis of developmental anomalies in comparison
      to the palpatory methods. The corrective and reconstructive surgery for the
      developmental anomalies of the female genital tract should be the domain of a
      specialized center. Increased awareness of the parents and the public, increase
      in environmental pollution has led to more frequent and earlier diagnosis of
      these malformations, which in turn has led to the shift in age for therapeutic
      interventions.

PMID- 12001765
TI  - [Antioxidant properties of estrogens].
AB  - The author expounded present state of knowledge concerning antioxidant properties
      of estrogens. Estradiol, apart from its main hormonal effect, probably displays
      two mechanisms of antioxidant action. One of them results from hydroxyphenolic
      structure of their molecule. Estradiol may donate hydrogen atoms from its
      phenolic hydroxyl group to lipid peroxyradicals what results in the termination
      of the chain reactions of cell membrane phospholipides, which are the key
      reactions in cell damage. Estradiol also inhibits oxidative modification of LDL
      lipoprotein which plays the main role in atherogenesis. The other mechanism of
      antioxidative action of estradiol is probably associated with its stimulatory
      effect on natural cellular antioxidant enzymes. Data on this subject are scarce
      and controversial. The mechanisms of antioxidant action of estrogens require
      further investigation.

PMID- 12001766
TI  - [Immunologic and genetic aspects of endometriosis physiopathology].
AB  - This article reviews the pathological mechanism of endometriosis. We concentrate
      on immunological and genetical factors which play a role in the developing of
      endometriosis. We present the possible network of interactions between immune
      cells, hormones and matrix metalloproteases system in the ectopic endometrial
      tissue.

PMID- 12001767
TI  - [Evaluation of expression and correlation between P53, BCL-2 and BAX proteins in
      ovarian neoplasms].
AB  - OBJECTIVES: Interactions between BCL-2 and other proteins regulating programmed
      cells death in ovarian carcinomas are poorly understood. DESIGN: The evaluation
      of expression of P53, BCL-2 and BAX proteins in ovarian carcinomas. The
      associations between oncoproteins studied and the histological structure, grade
      of differentiation and stage of disease were also analysed. MATERIAL AND METHODS:
      The expression of P53, BCL-2 and BAX was evaluated by immunoperoxidase technique
      (PAP) in tissue sections and corresponding cyst and/or ascitic fluid cells in
      individual patients with ovarian carcinoma. RESULTS: It was shown that the
      expression of P53 and BAX was comparable in tissue sections and cyst or ascitic
      fluid cells of individual patients, however the presence of BCL-2 was detected
      more frequently in tissue sections. No correlations between markers studied and
      histological subtypes and grade of carcinoma were found. Taking into account the
      relationship between P53, BCL-2 and BAX expression, it was possible to classify
      the studied ovarian carcinomas into four phenotypes. Ovarian cancers with
      phenotype P53+/BCL-2- were more frequent in III/IV degree FIGO stages whereas the
      phenotype P53-/BCL-2+ were identified mainly in patients in I/II degree FIGO
      stages. The progression of disease and death occurred more frequently in groups
      with phenotype P53+/BCL-2+ and P53-/BCL-2-. CONCLUSIONS: Our observations
      indicated that estimation of P53, BCL-2 and BAX protein expression may be
      important in the choice of the chemotherapy.

PMID- 12001768
TI  - [Evaluation of prenatal care intensity in the Brzezin region in 1987-98].
AB  - Antenatal medical care is one of the most important factors bearing an influence
      on the course of pregnancy and labour. The study group comprised 7307 pregnant
      patients who delivered in the regional Hospital in Brzezin. The women not taking
      advantage of antenatal care constituted 3.4% of all pregnant patients, those who
      had visited the gynaecological outpatient department less than 4 times during the
      pregnancy--15.4%, and those who had had 4 to 7 visits--57%, and 8 visits or more-
      23.8%. In 52.2% of cases antenatal care started early. During the period 1987
      1998 antenatal medical care systematically improved. The number of women seeking
      the doctor's advice early in their pregnancy and complying with the check-up
      schedules to at least satisfactory degree increased. The risk of late or
      insufficient compliance with antenatal care requirements was higher among the
      patients below 20 and over 34, singles, those with the fourth or subsequent
      pregnancy, and those who had completed elementary or vocational education.

PMID- 12001769
TI  - [Evaluation of fetal oxygen saturation (FSpO2) during the course of underwater
      labor].
AB  - During controlled, randomized prospective trials, fetal arterial hemoglobin
      saturation (FSpO2) was estimated during 25 underwater labors and compared to
      results obtained from 34 classical deliveries. Mean fetal hemoglobin saturation
      during the first stage of labor was similar in both groups while a gradual
      decreasing trend in fetal FSpO2 was noticed throughout the progress of labor. In
      the second stage of labor higher mean FSpO2 values were observed in the group of
      fetuses born underwater. The author emphasized in discussion that underwater
      labor constitutes delicate and mild procedure particularly for the fetus.

PMID- 12001770
TI  - [Clinical significance of echogenic amniotic fluid at term pregnancy].
AB  - PURPOSE: This study is aimed to determine the clinical significance of echogenic
      amniotic fluid. MATERIAL AND METHODS: I surveyed 9 at term pregnancies in which
      the amniotic fluid was echogenic. Morphologic characteristics of amniotic fluid
      were assessed from samples taken at amniocentesis or upon delivery within one day
      after last sonographic examination. RESULTS: In pregnancies with echogenic
      amniotic fluid, assessment revealed clear fluid in 4 cases (44.5%), vernix
      caseosa in 4 (44.5%), and meconium in 1 (11.0%). CONCLUSIONS: Echogenic amniotic
      fluid on prenatal sonography is not predictive of fetal distress.

PMID- 12001771
TI  - [Congenital agenesis of vagina and cervix].
AB  - A case of vaginal and cervical agenesis was presented. The mode of therapeutic
      procedure consisting of several stages was shown. Menstruation to abdominal
      cavity was stopped, using pharmacological agent. At the first step diagnostic
      laparoscopy was performed and artificial vagina was formed. During the second
      operation a junction of uterus with vagina was carried out. At present, the
      patient menstruates through vagina. The normal sexual function was achieved.

PMID- 12001772
TI  - [Intrauterine fetal death at term--imperfection of medical supervision methods or
      statistical-biological inevitability--attempt for discussion based on a case
      report].
AB  - There is a description of the case of unexplained intrauterine fetal death at
      term. The course of the pregnancy was regular. There were any sinister symptoms
      preceded and there were no malformations or other abnormalities observed
      thereafter. The preventive role of the more and more sophisticated antenatal
      monitoring is in the opinion of the authors questionable. Sudden prenatal and
      postnatal death seems to be an inevitable part of our existence. The similar
      conclusions from the present literature are quoted.

PMID- 12001773
TI  - [Expression of p-glycoprotein in malignant solid human tumors].
AB  - One of the main causes of cancer resistance to chemotherapy is multidrug
      resistance. The role of P-glyco-protein in different solid human cancers was
      assessed by taking into account clinico-pathological parameters. The application
      of inhibitors when multidrug resistance appeared was discussed. The participation
      of other proteins and enzymes in adding resistance to the cancer cells was
      stressed.

PMID- 12001774
TI  - [Magnetic resonance imaging in prenatal diagnosis].
AB  - Author discusses methods of magnetic resonance imaging and in status in the
      prenatal diagnosis as well as the impact of examination on the management plan
      for treatment of fetus and newborn.

PMID- 12001775
TI  - [Consequences of intrauterine hypoxia in the newborn].
AB  - In the above paper authors introduced current opinions regarding diagnosis,
      prevention and management in asphyxiated newborn infants with multiorgan
      disfunction and injury.

PMID- 12001776
TI  - Serum concentrations of markers of type I collagen metabolism in women taking
      monophasic oral contraceptives.
AB  - OBJECTIVES: To investigate serum concentrations of the carboxy-terminal
      propeptide of type I procollagen (PICP) and cross-linked carboxy-terminal
      telopeptide of type I collagen (ICTP), reflecting the rate of synthesis and
      degradation of the parent collagen respectively, in women using monophasic oral
      contraceptives. STUDY DESIGN: PICP and ICTP were estimated in 60 women taking 20
      micrograms of ethinyl estradiol (EE) + 150 micrograms of desogestrel (DSG) or 30
      micrograms of EE + 150 micrograms DSG over six months. RESULTS: Mean PICP
      concentration decreased in women receiving 20 micrograms of EE + 150 infinity g
      of DSG after three cycles of administration. However, after six months this value
      returned to a level comparable to the initial one. In women taking 30 micrograms
      of EE + 150 micrograms of DSG the mean concentrations of PICP did not change
      significantly throughout the period studied. None of the oral contraceptives
      noticeably influenced the concentrations of ICTP. CONCLUSION: Investigated oral
      contraceptives do not significantly affect the metabolism of type I collagen,
      however a transient decrease in its biosynthesis may be expected during the use
      of formulations containing 20 micrograms of EE.

PMID- 12001777
TI  - Evaluation of the antisperm antibodies in infertile couples afflicted with a
      cervical factor.
AB  - OBJECTIVES: The purpose of this study was to evaluate methods used for antisperm
      antibodies detection in infertility. METHODS: The studied cohort comprised 38
      infertile couples with a distinct cervical factor. Presence of antisperm
      antibodies and their levels in circulation were evaluated in sera samples of both
      partners and also in the cervical mucus and semen with the Latex Agglutination
      test. Western Blotting was applied as an additional method in antibody detection.
      We also assessed: the number of sexual partners, potentially allergizing sexual
      behaviour and other potentially sensitising factors. RESULTS: The positive
      antisperm antibodies were detected merely twice and only in one case there was
      evidence of insemination-impeding antisperm humoral response. The Western
      Blotting method enabled us to obtain a reaction to a range of sperm proteins
      which reacted with antibodies both in serum and in seminal plasma. CONCLUSIONS:
      Determination of infertility on immunological grounds on the basis of a single
      determinant on sperm presents little diagnostic value. In our view, the
      combination of patient's clinical status with immune-system response to a
      spectrum of sperm antigens provides means of infertility evaluation. We propose
      Western Blotting as an useful technique for detection of antisperm antibodies.

PMID- 12001778
TI  - [Ovarian hyperandrogenism in adolescent girls with menstrual disorders].
AB  - OBJECTIVES: In women with polycystic ovaries (PCO) hyperandrogenemia, an
      increased LH-concentration and a hightened ratio of LH/FSH are common. In
      adolescent hirsute girls with menstrual disorder, which may herald PCO in
      adulthood, ovarian hyperandrogenemia was under scrutiny. In most of them
      functional ovarian hyperandrogenism (FOH) is present in response to challenge
      with GnRH analog. It is not known whether FOH is involved in the pathogenesis of
      menstrual disorders in adolescent girls without hirsutism. MATERIAL AND METHODS:
      24 girls with menstrual disorder in the mean age of 17.5 +/- 1.6 years old were
      investigated and compared to the age matched group of girls with regular menses.
      Basal and GnRH stimulated levels of ovarian androgens and gonadotropins were
      measured and USG of the ovaries were performed in all girls. RESULTS: In over 50%
      of girls with menstrual disorder basal and stimulated 17 OH progesteron and
      androstenedione levels were found significantly higher as compared to the control
      groups. In all girls but three they were not associated with the polycystic
      structure of the ovaries. Only half of these girls had an increased LH/FSH ratio.
      CONCLUSIONS: Functional ovarian hyperandrogenism may be present in adolescent
      girls with menstrual disorder in spite of the absence of the clinical signs of
      hirsutism and polycystic structure of the ovaries.

PMID- 12001779
TI  - The long arm of abuse.

PMID- 12001780
TI  - Faith in America.

PMID- 12001781
TI  - The mind maze. Can 'distraction' be found in the brain's biochemistry?

PMID- 12001782
TI  - A better heart attack therapy. New research calls for more hospitals to be
      allowed to use angioplasty.

PMID- 12001783
TI  - Nursing homes finally get report cards.

PMID- 12001784
TI  - They know not what they do. Even in Rome, the U.S. cardinals still forgot the
      children.

PMID- 12001785
TI  - Germany's Columbine. A quiet European cathedral town is the tragic site of one of
      the bloodiest school massacres in history.

PMID- 12001786
TI  - The secrets of autism.

PMID- 12001787
TI  - Do french fries cause cancer?

PMID- 12001788
TI  - Interleukin-16 network in inflammation and allergy.
AB  - Interleukin (IL)-16 is a homotetramer of 14-kDa subunits discovered in 1982 as a
      T-cell-specific chemoattractant factor. IL-16 plays a role in trafficking of
      several immune cells and may be a major chemotactic signal for CD4+ cells. Here,
      we review some of the key biological actions of IL-16. Because this cytokine has
      been shown to affect the levels of many inflammatory mediators such as histamine,
      serotonin, regulated upon activation, normal T cell expressed and secreted
      (RANTES), and monocyte chemotactic protein-1 (MCP-1), and other cytokines such as
      IL-2, we investigated the effect of IL-16 on control and stimulated human
      umbilical cord blood-derived cultured mast cells after antigen challenge. We
      found that human recombinant IL-16 (0.2-200 ng/mL) does not affect either basal
      tryptase or IL-8 release or that induced by anti-immunoglobulin E activation. In
      accordance with other data in the medical literature, we conclude that the most
      important function of IL-16 is the chemoattraction of CD4+ cells.

PMID- 12001789
TI  - The effect of disodium cromoglycate, budesonide, and cyclosporin A on interleukin
      4, interleukin-5, and interleukin-13 secretions in Der p I-stimulated T cells
      from house dust mite-sensitive atopic and nonatopic individuals.
AB  - Disodium cromoglycate (DSCG), budesonide, and cyclosporin A (CsA) were the well
      known immunomodulators for the allergic and immunologic diseases clinically. In
      this study, we evaluated the characteristics of inhibition on cytokine synthesis
      of Der p I-stimulated T cells by the same inhibiting concentrations of DSCG,
      budesonide, and CsA in house-dust mite antigen (Der p I)-specific atopic and
      nonatopic healthy individuals. Seven house dust mite allergen specific patients
      were recruited for this study. Seven healthy volunteers were included on the
      basis of negative allergic manifestations and low serum immunoglobulin E values.
      Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of
      recombinant interleukin (rIL)-2 with or without budesonide, DSCG, CsA, and Der p
      I for 48 hours. Cells were stained with anti-CD4 fluorescein isothiocyanate
      conjugated monoclonal antibody, and then anti-human IL-4 phycoerythrin, IL-5, or
      IL-13 monoclonal antibody, respectively, was added to both blocked and stained
      samples. Incubation of PBMC from atopics with each immunomodulator and Der p I
      resulted in the reduction of IL-4 secretion compared with Der p I alone
      stimulation. However, IL-4 secretion in PBMC from nonatopics was not reduced with
      DSCG and Der p I stimulation. IL-4, IL-5, and IL-13 secretions of PBMC from
      atopics were significantly decreased after incubation with each immunomodulator
      and Der p I, compared with after incubation with Der p I alone. These results
      might be considered to show either that DSCG has a selective inhibiting effect on
      cytokine production in T cells from atopics or is a weak inhibitor of cytokine
      secretions compared with budesonide and CsA at even strength for the inhibition
      of lymphocyte proliferation in normal, healthy individuals.

PMID- 12001790
TI  - Hypodense eosinophils: characterization of surface molecule expression.
AB  - Distinct eosinophil populations have been characterized on the basis of
      discontinuous Percoll density gradients. In peripheral blood, normal individuals
      show a low number of normodense and hypodense eosinophils, contrasting with the
      high amount of hypodense cells in patients who have allergies. To characterize
      these two eosinophil populations, we analyzed membrane expression of several
      antigens and cytokine receptors in normodense and hypodense eosinophils from
      patients who have allergies and controls. Hypodense eosinophils expressed higher
      levels of CD122, CD69, and CD4 in both patients with allergies and control
      individuals when compared to normodense eosinophils. The expression of CD125,
      CD124, CD25, CD132, and CD23 were similar in both cell types.

PMID- 12001791
TI  - Major allergen measurements: sources of variability, validation, quality
      assurance, and utility for laboratories, manufacturers, and clinics.
AB  - The isolation and characterization of prominent allergenic proteins or
      glycoproteins is an important step in the development of allergenic extracts
      exhibiting improved definition, consistency, and clinical utility. Quantitative
      analyses specific for major allergenic components currently are being performed
      in numerous corporate and academic laboratories but have not been validated
      within or across laboratories in a systematic manner. In our laboratory,
      validation of double-bind (sandwich) ELISA assays for a diverse group of major
      allergens or extract components revealed a number of critical assay variables and
      reagent incubation conditions that directly influenced the precision, accuracy,
      specificity, and robustness of these tests. Data from ELISA methods for six
      allergens (Dermatophagoides farinae Der f 1, Alternaria Alt a 1, dog albumin, dog
      Can f 1, fire ant Sol i 3, and yellow jacket venom Ves 5) showed that up to
      twofold differences in results were observed when analysts or microplates were
      varied. Analyses of dog allergens using multiple reagents and concentrations
      indicated that twofold variations in results also can be produced by distinct
      combinations of materials or incubations from different assay steps. Data from
      Can f 1 and egg white analyses produced up to fivefold differences in antigen
      concentrations based on changes in the capture antibody source (mouse monoclonal
      versus rabbit polyclonal) or storage buffer. These results suggest that
      differences in major allergen concentrations reported by different testing
      laboratories may be related to assay differences as well as extract variations
      and raise questions as to the accuracy of major allergen concentrations and
      therapeutic dose recommendations reported at regional and national allergy
      meetings. Validated double-bind ELISA methods may be well suited for consistency
      monitoring and standardization of extracts provided that reference materials,
      reagent qualifications, and interlaboratory comparability are defined precisely.

PMID- 12001792
TI  - Laryngeal dysfunction: a common cause of respiratory distress, often misdiagnosed
      as asthma and responsive to antireflux therapy.
AB  - Asthma is diagnosed frequently in patients with respiratory distress. However,
      laryngeal dysfunction, a common cause of dyspnea, may masquerade as asthma. This
      study investigated 158 consecutive patients referred to an allergy practice with
      a diagnosis of asthma. Pulmonary function testing with flow volume loops were
      used to separate the patients into four groups. These groups consisted of
      patients with asthma alone in 32%, asthma and laryngeal dysfunction in 16%,
      laryngeal dysfunction in 26%, and another group not meeting these criteria in
      25%. Thirty patients, 10 each from the first three groups, were treated with
      antireflux medication and reevaluated. Symptom evaluation observed inspiratory
      difficulties in 73% of the laryngeal dysfunction group compared with 2% of the
      asthma group (p < 0.0001). Expiratory problems were present in 7% of the
      laryngeal dysfunction group and 71% of the asthma group (p < 0.0001). The
      laryngeal dysfunction group only had a 29% beneficial response to Albuterol
      inhalation compared with a 92% response in the asthma group (p < 0.0001). The
      laryngeal dysfunction group responded significantly less to both inhaled and oral
      steroids (p = 0.002). Among the 30 patients treated with antireflux medications,
      the peak flows improved by 38.7% in the laryngeal dysfunction group compared with
      14.8% in the asthma group (p = 0.01).

PMID- 12001793
TI  - Allergen cross-reactivity between proteins of the latex from Hevea brasiliensis,
      seeds and pollen of Ricinus communis, and pollen of Mercurialis annua, members of
      the Euphorbiaceae family.
AB  - Allergen cross-reactions among three strongly sensitizing Euphorbiaceae species,
      i.e., the rubber tree (Hevea brasiliensis), castor bean (Ricinus communis), and
      the Mediterranean weed Mercurialis annua were studied in Finnish patients (n =
      25) allergic to natural rubber latex (NRL), but with no known exposure to castor
      bean or M. annua, and French patients allergic to castor bean (n = 26) or to M.
      annua (n = 9), but not to NRL. In immunoglobulin E (IgE)-immunoblotting, 28% of
      NRL-allergic patient sera recognized castor bean seed and 48% reacted to castor
      bean pollen proteins. Likewise, 35% of the NRL-allergic patient sera bound to M.
      annua pollen allergens. Nineteen percent of castor bean-allergic patients showed
      IgE to NRL and 8% to M. annua proteins. Sera from patients allergic to M. annua
      reacted in 44% to NRL, in 56% to castor bean seed, and in 78% to castor bean
      pollen proteins. In immunoblotting, castor bean seed extract inhibited the
      binding of NRL-reactive IgE to 20 kDa, 30 kDa of NRL, and 55 kDa of proteins; NRL
      extract, in turn, inhibited the binding of castor bean-reactive IgE to 14, 21-22,
      29, and 32-34 kDa of castor bean proteins. In ELISA inhibition, NRL extract
      inhibited 33% of the binding of M. annua--reactive IgE of pooled sera to M. annua
      pollen. In conclusion, allergen cross-reactivity in vitro was observed among
      three botanically related Euphorbiaceae members, H. brasiliensis, R. communis,
      and M. annua, but the molecular specificity of the observed cross-reactions as
      well as their clinical significance remains to be elucidated. Allergen cross
      reactivity should be taken into account in diagnostic work.

PMID- 12001794
TI  - Severe tomato allergy (Lycopersicon esculentum).
AB  - Although tomatoes are a commonly consumed food, severe allergic reactions to
      tomatoes are unusual or rarely reported. Previously reported allergic
      manifestations to tomato include urticaria/angioedema, dermatitis, oral allergy
      syndrome, rhinitis, and abdominal pain. The aim of this study was to report two
      patients with significant immediate hypersensitivity reactions to tomato and
      characterize the responsible allergen. We reviewed the history and documentation
      of tomato-specific immunoglobulin E (IgE) of two patients with adverse symptoms
      after ingesting tomato. Fresh tomato extracts prepared from the skin, seeds, and
      flesh of red, ripe tomatoes were evaluated for total protein content and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to
      characterize the tomato protein. IgE enzyme-linked immunosorbent assay (ELISA)
      using the patients' serum against the various tomato extracts was accomplished
      and IgE immunoblot was performed. Percutaneous skin tests or radioallergosorbent
      tests (RASTs) were positive to tomato in both patients. Both adults experienced
      laryngeal edema and one had anaphylaxis. Similar total protein contents were
      found in each of the tomato extracts and gel electrophoresis revealed similar
      protein profile for skin and seed extracts with protein bands discernible at
      molecular weights of 21, 33, and 43 kDa. One patient reacted specifically to a 43
      kDa protein band on IgE immunoblot. The two cases show that severe allergic
      reactions to tomato occur in adults and one is associated with IgE binding to a
      43-kDa protein.

PMID- 12001795
TI  - The anti-inflammatory actions of azelastine.

PMID- 12001796
TI  - Episodic swelling in a pregnant woman from Bangladesh: evaluation and management
      of angioedema in pregnancy.
AB  - Deficiencies in the C1 inhibitor protein are central to the pathogenesis of
      acquired and hereditary angioedema syndromes. Here, we present a case of a
      patient who developed recurrent episodes of angioedema during pregnancy. We
      discuss the evaluation of patients presenting with angioedema, describe the
      mechanisms by which deficiencies in C1 inhibitor contribute to the development of
      angioedema, and focus on the natural history and clinical management of the
      pregnant patient with angioedema.

PMID- 12001797
TI  - Virus-provoked rhinitis in patients who have allergies.
AB  - The most common illnesses in humans are the respiratory tract infections caused
      by viruses. When limited to the upper respiratory region, these infections often
      are designated as "a common cold." Viruses commonly associated with these upper
      respiratory infections (URI) include rhinoviruses (RVs), respiratory syncytial
      virus, influenza virus, parainfluenza virus, corona virus, and adenoviruses.
      Clinical observations have suggested that patients with allergic rhinitis and
      asthma experience more pronounced symptoms during a viral URI than patients who
      do not have allergies and who are infected with the same virus under similar
      circumstances. Using an experimental virus infection model in human volunteers
      with and without allergic rhinitis, several groups of clinical investigators have
      studied the effects of experimental RV infections. These observations indicate
      that the experimental virus infection may induce host responses that provoke
      enhanced immunoglobulin E (IgE) synthesis. Whether this translates into enhanced
      symptoms has been suggested in one study but not in another. This article will
      review these studies, which suggest that it is the host response to the virus and
      not the virus itself that plays the major role in symptom pathogenesis.

PMID- 12001798
TI  - Clinical ethics committees: clinician support or crisis management?

PMID- 12001799
TI  - The Clinical Ethics Committee at Barts and the London NHS Trust: rationale,
      achievements, and difficulties.

PMID- 12001800
TI  - The Clinical Ethics Committee at the Royal United Hospital--Bath, England.

PMID- 12001801
TI  - Clinical ethics committees: opportunity or threat?

PMID- 12001802
TI  - Ethics and Clinical Ethics Committee Education.

PMID- 12001803
TI  - Ethical review of innovative treatment.

PMID- 12001804
TI  - Resource allocation decisions in U.K. healthcare: do ethics committees have a
      role?

PMID- 12001805
TI  - Poor communications, cultural barriers impacting quality of health care for
      minorities.
AB  - A new survey released last month by the Commonwealth Fund shows that for a range
      of health care quality factors--such as patient/provider communications, cultural
      and linguistic barriers, and access to health care and insurance coverage-
      minority Americans are not faring as well as whites.

PMID- 12001806
TI  - Using Six Sigma to make a difference in health care quality.
AB  - For years, the health care industry has borrowed ideas and initiatives from other
      industries to promote and enhance quality. The most recent idea to capture the
      interest of many in the health care field has been Six Sigma, which has been used
      and refined during the past two decades by top corporations. This issue looks at
      how five organizations are using the Six Sigma management process--with its
      reliance on data, statistical analysis, and change--to enhance quality.

PMID- 12001807
TI  - E 64.

PMID- 12001808
TI  - Lerdelimumab.

PMID- 12001809
TI  - MDL 28170.

PMID- 12001810
TI  - MDX RA 4197X-RA, monoclonal antibody ricin A.

PMID- 12001811
TI  - SJA 6017.

PMID- 12001812
TI  - Profile summary.

PMID- 12001813
TI  - AFO 150. Imagent, Imavist.

PMID- 12001814
TI  - Enalapril/nitrendipine.  ENEAS, nitrendipine/enalapril.

PMID- 12001815
TI  - Human haemoglobin--Northfield. PolyHeme.

PMID- 12001816
TI  - Influenza virus vaccine live intranasal--Aviron. Flumist, influenza vaccine live
      intranasal.

PMID- 12001817
TI  - LeuTech.

PMID- 12001818
TI  - Mismatched double-stranded RNA. Ampligen, Oragen, polyI:polyC12U.

PMID- 12001819
TI  - Nitisinone. Ntbc, Orfadin.

PMID- 12001820
TI  - Triamcinolone acetonide hydrofluoroalkane inhalation--aventis.

PMID- 12001821
TI  - Tolterodine: selectivity for the urinary bladder over the eye (as measured by
      visual accommodation) in healthy volunteers.
AB  - OBJECTIVE: Tolterodine exhibits a favourable selectivity for the urinary bladder
      over salivary glands in vivo, in the anaesthetised cat, whereas oxybutynin shows
      the opposite selectivity profile in this model. This study further evaluated the
      selectivity profiles of tolterodine and oxybutynin by comparing the effects on
      bladder function and visual accommodation in the same individuals. METHODS: In a
      double-blind, randomised, four-way crossover study, 16 healthy volunteers
      received single oral doses of tolterodine 5 mg and oxybutynin 2.5, 5 and 7.5 mg.
      Voiding parameters were assessed for 12 hours post-dose, along with visual
      accommodation (near point of vision) at regular intervals. RESULTS: A dose
      dependent increase in maximum bladder capacity was observed for oxybutynin [2.5
      mg (+35%), 5 mg (+45%) and 7.5 mg (%)]. The effect of tolterodine 5 mg on bladder
      capacity was approximately twice (+93%) that seen after oxybutynin 5 mg and the
      onset of the effect was more rapid with tolterodine. Effects on visual
      accommodation were also dose-dependent for oxybutynin (maximum changes in near
      point of vision were 13%, 20% and 29%, respectively). The maximum change observed
      after tolterodine 5 mg was the same as after oxybutynin 5 mg (i.e. 20%).
      CONCLUSIONS: Tolterodine seems to exhibit selectivity for the bladder over the
      eye. Therefore, these results suggest that the normal dosage of tolterodine (2 mg
      twice daily) may have less effect on visual accommodation than the equivalent
      dosage of oxybutynin (5 mg three times daily) in patients with an overactive
      bladder.

PMID- 12001822
TI  - Oxybutynin intravesical--situs.  I-oxy.

PMID- 12001823
TI  - S-oxybutynin.

PMID- 12001824
TI  - Efficacy of N-acetylcarnosine in the treatment of cataracts.
AB  - PURPOSE: To evaluate the effects of 1% N-acetylcarnosine (NAC) solution on lens
      clarity over 6 and 24 months in patients with cataracts. TRIAL DESIGN:
      Randomised, placebo-controlled study. PARTICIPANTS: 49 subjects (76 affected
      eyes) with an average age of 65.3 +/- 7.0 years with a diagnosis of senile
      cataract with minimum to advanced opacification in various lens layers. METHODS:
      26 patients (41 eyes) were allocated to topical NAC 1% eyedrops twice daily. The
      control group consisted of 13 patients (21 eyes) who received placebo eyedrops
      and 10 patients (14 eyes) who did not receive eyedrops. MAIN OUTCOME MEASURES:
      All patients were evaluated at entry and followed up every 2 months for a 6-month
      period (trial 1), or at 6-month intervals for a 2-year period (trial 2), for best
      corrected visual acuity and glare testing. In addition, cataract was measured
      using stereocinematographic slit-images and retro-illumination examination of the
      lens. Digital analysis of lens images displayed light scattering and absorbing
      centres in two- and three-dimensional scales. RESULTS: The overall intra-reader
      reproducibility of cataract measurements (image analysis) was 0.830, and glare
      testing 0.998. After 6 months, 90% of NAC-treated eyes showed improvement in best
      corrected visual acuity (7 to 100%) and 88.9% showed a 27 to 100% improvement in
      glare sensitivity. Topographic studies indicated fewer areas of posterior
      subcapsular lens opacity and 41.5% of treated eyes had improvement in image
      analysis characteristics. The overall ratios of image analysis characteristics at
      6 months compared with baseline measures were 1.04 and 0.86 for the control and
      NAC-treated group, respectively (p < 0.001). The apparent benefits of treatment
      were sustained after 24 months' treatment. No treated eyes demonstrated worsening
      of vision. The overall visual outcome in the control group showed significant
      worsening after 24 months in comparison with both baseline and the 6-month follow
      up examination. The overall clinical results observed in the NAC-treated group by
      the 24-month period of examination differed significantly (p < 0.001) from the
      control group in the eyes with cortical, posterior subcapsular, nuclear or
      combined lens opacities. Tolerability of NAC eyedrops was good in almost all
      patients, with no reports of ocular or systemic adverse effects. CONCLUSION:
      Topical NAC shows potential for the treatment and prevention of cataracts.

PMID- 12001825
TI  - [Treatment of asymptomatic patients who have survived extensive myocardial
      infarction].
AB  - Most patients that survive an acute myocardial infarction remain symptomatic,
      mainly with manifestations of heart failure, arrhythmias, or residual ischemia;
      however there is a group of patients without symptoms that must be studied
      because their evolution could be life threatening, specially if they have left
      ventricular dysfunction, arrhythmias, severe coronary artery disease, comorbid
      diseases, are older patients or have history of previous myocardial infarctions.
      An exercise treadmill test must be done as well as Holter monitoring,
      radionuclide perfusion imaging echocardiography with or without drugs, nuclear
      magnetic resonance and cardiac catheterization with coronary angiography to
      determine pharmacologic treatment and prompt revascularization.

PMID- 12001826
TI  - [Heart arrhythmia in the elderly].
AB  - Cardiac arrhythmias are a major problem in elderly persons, because of the high
      prevalence of underlying heart disease and hypertension, arrhythmias are
      associated with significant morbidity and mortality in this age group. Atrial
      fibrillation (AF) is the most common sustained arrhythmia encountered in clinical
      practice. Its incidence increases with age and the presence of structural heart
      disease. It is a major cause of stroke, especially in the elderly. Although the
      established principles of evaluation and management of cardiac arrhythmias apply
      to all age groups, management in the elderly patient is especially challenging
      because of increased risk of interventional and pharmacologic therapies, altered
      pharmacokinetics of drugs, and sometimes unclear long-term benefits in the older
      patient.

PMID- 12001827
TI  - [Counterpulsation balloon and ventricular support].
AB  - There are a number of conditions that give rise to or result from a failing heart
      and that require assisting or replacing the insufficient or abnormal ventricular
      function. In addition, in attempting to treat these conditions medically or
      surgically, a wide range of mechanical assisted ventricular devices has been
      developed, which can potentially address these conditions. Balloon
      counterpulsation was first employed clinically in 1968 by Kantrowitz. The
      increased coronary perfusion that results from Intraaortic Balloon Pump (IABP)
      inflation during diastole and the decreased afterload and enhanced cardiac output
      from IABP deflation during systole is theoretically the ideal therapy for
      cardiogenic shock, in which the cardiac output is low and the systemic vascular
      resistance high. The most obvious efficacy, both theoretically and empirically,
      is in the setting of ischemia resulting from coronary artery disease. Likewise,
      the IABP provides an effective and safe form of mechanical support in many high
      risk patients undergoing coronary angioplasty. Contraindications for IABP use
      include aortic valve insufficiency and aortic dissection. Reported complication
      rates vary, but are probably in the range of 5-10%. Most incidents are related to
      thromboembolism, uncommonly related to arterial trauma and limb ischemia.

PMID- 12001828
TI  - [Pacemaker stimulation in dilated and hypertrophic myocardiopathies: should its
      use be stratified?].
AB  - New indications for permanent cardiac pacing have been developed in recent years,
      with numerous studies demonstrating improved clinical outcomes in many disorders.
      These techniques have been used in hypertrophic obstructive cardiomyopathy and
      dilated cardiomyopathy, and many physiological bases and clinical studies justify
      their application. In dilated cardiomyopathy and heart failure with
      intraventricular conduction delay, abnormal electrical depolarization of the
      heart results in mechanical asynchrony of the ventricles. Tricameral pacing
      (atrial-based biventricular) offers an alternative and conditions ventricular
      synchronization. The MUSTIC study, a controlled, randomized, crossover study,
      showed promising results, significantly improving exercise tolerance and quality
      of life, and increasing in diastolic ventricular filling period. Several ongoing
      randomized, controlled clinical trials should provide more definitive data on
      safety, efficacy, and decreased mortality. Hypertrophic obstructive
      cardiomyopathy has many therapeutic approaches such as, medical treatment, dual
      chamber pacing, surgery, and transcatheter septal ablation. Dual chamber pacing
      has been shown to improve symptoms and hemodynamic variables in patients severely
      symptomatic. However, randomized clinical trials (PIC and M-PATHY) have not shown
      conclusive evidence regarding the long-term benefit from pacing in these
      patients. Moreover, relationship between reduction in the intraventricular
      gradient and improvement of symptoms is controversial; there might be a
      significant placebo effect. Cardiac pacing is an alternative therapy for selected
      patients with hypertrophic cardiomyopathy, but very careful screening of patients
      is mandatory.

PMID- 12001829
TI  - [Treatment of perioperative arterial hypertension].
AB  - Pulmonary hypertension (PH) is a condition frequently associated to many
      cardiovascular diseases and can become a complication in the postoperative
      period. The success of the treatment depends of the preoperative assessment, an
      adequate anesthetic and surgical technique and appropriate use of drugs during
      and after surgery. The presence of PH during the postoperative period can
      compromise right ventricular function, left ventricular filling and, hence,
      global perfusion. In recent years, administration of nitric oxide (NO) has been
      useful for the treatment of cardiovascular conditions associated to pulmonary
      hypertension. In this paper, we review the current strategies for the management
      of this condition.

PMID- 12001830
TI  - [Is there a malignant neurocardiogenic syncope?].
AB  - There is a subset of patients with neurocardiogenic syncope among whom syncopal
      recurrences are frequent and without prodromic symptoms, or have a traumatic
      outcome. For this subgroup the term "malignant neurocardiogenic syncope" has been
      proposed. Frequently, these patients suffer from syncopes that are accompanied by
      profound bradycardia and prolonged asystole (more than 5 seconds). Although in
      the literature the term malignant is used as equal to syncope with prolonged
      asystole, this practice could lead to prognostic and therapeutic errors. The
      present article describes its clinical features, the usefulness of head-up tilt
      test for its therapeutic evaluation, and the wide variety of treatments that have
      been proposed including beta-adrenergic blockade, DDD pacemakers, and repeated
      tilt training program.

PMID- 12001831
TI  - [Stratification of coronary risk].
AB  - Coronary atheroselerosis constitutes the fifth leading cause of global disease
      burden and the leading cause in developed societies. Coronary artery disease is
      the leading cause of morbidity and mortality in the, United States, Western
      industrialized societies; in our country, it has become a real health problem.
      Compelling epidemiologic and clinical data have demonstrated that elevated total
      cholesterol levels, high blood pressure, and diabetes mellitus correlate with
      increasing coronary artery disease mortality. Risk factors modification in the
      general public and persons at high risk offers the best opportunity for
      effectively reducing the prevalence of coronary heart disease.

PMID- 12001832
TI  - [Heparins: from conventional to current approaches in the management of acute
      coronary ischemic syndromes].
AB  - The use of heparins in acute coronary syndromes has been established as
      antithrombine indication. In acute myocardial infarction, it is considered an
      adjunct therapy to reperfusion strategies. In patients with angina, this
      antithrombine therapy experts a synergic effect with antiplatelet drugs, which
      also have an antithrombine effect. This pharmacological information movides the
      possibility to use the traditional unfractioned heparin (UFH) and low molecular
      heparin (LMH), both are antithrombine drugs. The advantage of these low molecular
      heparins is their biodisponibility and easier use. Both types of heparins are
      relevant since there is valid information establishing that LMH is useful in
      acute coronary syndromes. Such as acute myocardial infarction (AMI), yielding
      better results than the UFH. Newer drugs, the pentasaccharides, have been
      reported recently, which. Newer drugs are small fractions of heparin, with
      antithrombine effects and which seem to be more powerful and effective offering
      better results. These drugs have been named pentasaccharides.

PMID- 12001833
TI  - [Interatrial communication in patients over 40 years of age].
AB  - Surgical treatment of atrial septal defect in patients older than 40 years is a
      subject of controversy. We compared the outcome in patients medically treated
      after the age of 40, with the long-term outcome in a similar group of patients
      after surgical closure. We conclude that surgical closure was superior to medical
      treatment. According to our results, surgical treatment must be performed as soon
      as possible, even if the symptoms of the functional status seem to be minimal.

PMID- 12001834
TI  - [Risk stratification in heart surgery].
AB  - Risk scores have been important in patient assessment, such as, age, severity of
      heart disease, and comorbidity in patients undergoing heart surgery. Several risk
      scores have been developed to predict mortality after heart surgery. This paper
      analyzes data of the world, cardiac surgery reporting system, which contains
      information on cardiac preoperative risk factors, and postoperative
      complications.

PMID- 12001835
TI  - [Specific dilated myocardiopathy. Chronic chagasic cardiopathy at the National
      Institute of Cardiology Ignacio Chavez].
AB  - Cardiomyopathies are a heterogenous group of heart ailments. Some of them are
      primary myocardial diseases and are classified as dilated, hypertrophic,
      restrictive and arryhithmogenic. Dilated cardiomyopathies (DCs) are the most
      common. Sometimes it is possible to identify an etiologic agent, in that case we
      talk about a specific dilated cardiomyopathy. Here in, we review one of these
      specific DCs, the so called Chronic Chagasic Cardiopathy (CCC) from the point of
      view of our personal experience at the Instituto Nacional de Cardiologia "Ignacio
      Chavez". Chagas' disease is present in Mexico, therefore CCC is also present. We
      estimate that 5,000 people, suffer CCC with severe symptoms. In Mexico, Chagas'
      disease occurs below the Tropic of Cancer and between 2,000-2,500 m above sea
      level, in this area there is a real risk for vectorial infection, mainly in rural
      villages. Clinical diagnosis should be supported by epidemiological and
      seroepidemiological confirmatory data. There is not appropriate therapy yet for
      this condition.

PMID- 12001836
TI  - [Atherosclerosis and inflammation].
AB  - Atherosclerosis is a disease of the large arteries. There are several risk
      factors, mainly genetic and environmental, associated with atherosclerosis.
      Recently acquired knowledge has clearly shown that a prominent role is played by
      several inflammatory mechanisms in the pathogenesis of this disease. Several pro
      inflammatory molecules such as LDL, macrophage colony stimulating factor, and
      adhesion molecules, deserve special mention because of their major role in the
      inflammatory response that takes place in atherosclerosis.

PMID- 12001837
TI  - [Pharmacology of inotropic agents].
AB  - High-risk patients, during anesthesia and after surgery present changes in
      pharmacokinetics (biotransformation reactions, renal clearance, drug
      interactions, etc.) modifying the usefulness of most drugs, cardiac inotropics
      included. This group of substances is formed by adrenergic agents,
      phospodiesterase inhibitors and digitalis compounds. Adrenergic agents are the
      catecholamines, adrenaline (A), noradrenaline (NA) and dopamine (D), plus
      dopaminergic agonists as dobutamine and pirbuterol. Phosphodiesterase inhibitors,
      as amrinone and milrinone, produce their inotropic action by preserving cyclic
      adenosine monophosphate (AMPc) from its intracellular catabolism. Recent studies
      on the utility of digitalis compounds demonstrated the valuable applicability of
      digoxin in chronic and acute heart failure. Another group of substances whose
      mechanism of action differs from that of the inotropics, offers future utility in
      high risk patients, they include: inhibitors of nitric oxide sintases,
      natriuretic atrial peptide inhibitors, Q-10 coenzyme, endothelin antagonists, and
      anti-tumoral necrosis factor.

PMID- 12001838
TI  - [Three-chamber pacemakers (ventricular resynchronization therapy)].
AB  - The medical treatment of patients with Congestive Heart Failure, functional class
      III-IV, has improved the quality of life, but have not reduced mortality. One
      group of these patients courses with intraventricular conduction delay and
      interventricular asynchrony, which worsens ventricular function.
      Resynchronization therapy is a novel alternative for the management of these
      individuals.

PMID- 12001839
TI  - [Impact of primary and secondary prevention on morbidity and mortality of
      ischemic cardiopathy].
AB  - Coronary artery disease (CAD) is the major cause of death in most developed
      countries and in many developing countries like Mexico. Epidemiologic studies
      initiated in the middle of the last century found that hypercholesterolemia,
      hypertension, tobacco smoking, diabetes mellitus, and other conditions are
      important precursors of atherosclerosis. With this knowledge, prevention of CAD
      was started. Some countries implemented a population strategy aimed at improving
      health-oriented behavior, mainly nutrition, smoking, and physical exercise in the
      entire population. The favorable changes in risk factors and better medical
      treatment for CAD patients have resulted in decreased coronary mortality over the
      past three decades. Randomized trials of antihypertensive treatment have shown
      that reduction of blood pressure leads to a decreased incidence of stroke and
      coronary events. Similarly, large secondary and primary prevention clinical
      trials of statin therapy have conclusively demonstrated the benefit of
      cholesterol lowering in preventing coronary morbidity and mortality. Despite this
      large body of scientific evidence, surveys in different countries show that in
      the population at large and particularly, in patients with documented CAD,
      preventive medical therapies are underutilized and, as a consequence, many
      patients are not achieving the recommended goals. Measures that increase
      compliance by both clinicians and patients to regimens with proven benefits are
      urgently required.

PMID- 12001840
TI  - [Mechanism of cellular toxicity induced by digitalis compounds. Study with
      ouabain].
AB  - The toxic effect of digitalis compounds at cell level produces an intracellular
      Ca2+ overload and a decrease in intracellular concentrations of K+. Since Ca2+
      and K+ are critical modulators of life and death, the purpose of this study was
      to explore the cell death pathway activated through the ionic imbalance provoked
      by digitalis intoxication. We present results of cell toxicity in a study
      performed with ouabain acting on a HeLa cells culture and on guinea pig heart
      myocites under ouabain intoxication. RESULTS: In tissue culture, ouabain produced
      inhibition of cell viability in a time and dose dependent manner. Through
      ethidium-bromide staining, nuclear condensation and fragmentation were observed.
      The electrophoretic analysis of nuclear DNA in agarose gel showed a degradation
      pattern characteristic of apoptosis. In histologic sections of guinea pig heart
      under ouabain intoxication (50-60% of lethal doses), in situ cell death was
      detected by in situ DNA TUNEL labeling. We conclude that the electrical and
      physiologic imbalance produced by toxic doses of ouabain activates mechanisms
      that cause cell death via apoptosis in heart myocites and fast growing cells.

PMID- 12001841
TI  - [Pharmacologic treatment of patients with arterial hypertension. Parameters to be
      considered when choosing a therapeutic approach].
AB  - The decision to treat, or not treat, uncomplicated mild hypertension should be
      based on a formal estimate of absolute cardiovascular risk and not on an
      arbitrary blood pressure threshold. The decision to initiate pharmacologic
      treatment requires consideration of the degree of blood pressure elevation, the
      presence of target organ damage, and the presence of clinical cardiovascular
      disease or other risk factors. Special considerations include demographic
      characteristics, concomitant diseases that may be beneficially or adversely
      affected by the antihypertensive agent chosen, quality of life, cost, and use of
      other drugs that may lead to drug interactions. Diuretics, beta-blockers or ACE
      inhibitors may be used as first-step drug therapies for the treatment of
      uncomplicated hypertension. Genetic factors may contribute to interindividual
      differences in responses to antihypertensive drug therapy. Knowledge of
      polymorphic variation in these genes will help to predict individual patients'
      blood pressure responses to antihypertensive drug therapy and may also provide
      new insights into molecular mechanisms responsible for elevation of blood
      pressure.

PMID- 12001842
TI  - [Septal ablation in the treatment of hypertrophic myocardiopathy].
AB  - Hypertrophic cardiomyopathy is a relative frequent disease and probably the most
      common genetic transmitted cardiovascular disease. Fortunately, the more
      aggressive varieties of the disease represent the less common manifestation of
      it. Outflow left ventricular obstruction is present in about 25 to 30% of the
      cases. Recently, septal ablation by means of the selective alcohol injection in
      left anterior descendent septal branches was introduced as a therapeutic
      alternative in cases associated with left ventricular outflow obstruction.
      Results with this technique have been encouraging with a success rate over 90%,
      and a low rate incidence of complications and mortality. These results are
      similar to those of surgical myectomy. We review indications, technique, and
      results obtained with this procedure.

PMID- 12001843
TI  - [Three-dimensional echocardiography in the diagnosis of cardiopathies].
AB  - The ability to visualize with dynamic 3D views the images obtained from the 2D
      study was the obviously next step in the evolution of echocardiography. Today,
      thanks to the technological evolution, the capability of obtaining and processing
      images with computers support has emerged with a great potential. Three
      dimensional echocardiography facilitates spatial recognition of intracardiac
      structures, is surpassing the experimental phase quickly and its accuracy has
      been validated in vivo.

PMID- 12001844
TI  - [Dynamic echocardiography in coronary risk stratification].
AB  - The prognostic value of some coronary risk factors related to
      Stress/Echocardiography was analyzed. The most important prognostic factors
      during an abnormal study are: presence and time of beginning, severity and
      extension of the myocardial ischemic changes.

PMID- 12001845
TI  - [Mechanisms of myocardial damage progression in heart failure].
AB  - Cardiac Failure is an increasing health problem in the world. Several mechanisms
      have been proposed as the cause of this epidemiological transition. The main
      reason is the increase in the survival of patients with coronary heart disease
      and the improvement in the management of cardiac failure with new drugs.
      Knowledge of new mechanisms including gene regulation, extracelullar matrix
      function, intracardiac vessels, neuroendocrine interrelations, inflammatory
      activity, immune balance, signalling intracellular and extracellular cascade, and
      mechanical integrity, have permitted a better and rational approach. The
      influence of paradigms such as endothelin system, sympathovagal balance,
      oxidative system, angiotensin receptors, aldosterone receptors have been
      demonstrated on progression of the cellular damage's patients with cardiac
      failure. Apoptosis is recognized as a common final way. In this review all these
      topics are analyzed. Emphasis is made on the new therapeutics strategies of
      treatment.

PMID- 12001846
TI  - [Indications and results of the pharmacologic treatment of angina pectoris].
AB  - The pharmacological treatment of the angina pectoris syndromes consists of: a)
      anti-ischemic therapy to relieve the symptoms and improve the quality of life, b)
      treatment aimed at preventing myocardial infarction and death, and c) measures to
      modify or reduce the risk factors for coronary disease. Revascularization
      procedures, coronary artery bypass grafting, or percutaneous coronary
      interventions, are used to improve prognosis, relieve symptoms, prevent ischemic
      complications, and improve functional capacity. In patients with mild angina,
      medical therapy, percutaneous coronary interventions and coronary artery bypass
      surgery are all reasonable options. However, there are indications for
      pharmacological treatment in the great majority of patients with angina. After a
      revascularization procedure the patient should continue to receive antiplatelet
      agents and follow a program of coronary risk factors modification.

PMID- 12001847
TI  - [Eisenmenger's syndrome. Advances in pathobiology and treatment].
AB  - The term Eisenmenger Syndrome is used to refer to any systemic to pulmonary
      congenital communication causing pulmonary vascular obstructive disease (PVOD)
      severe enough as to produce bidirectional or reversed shunt. Once established,
      the PVOD deteriorates the quality of life and limits the survival of the patients
      with congenital heart disease. In the last decade, there has been a significant
      advance in the knowledge of the pathobiology of PVOD. Potentially important
      pathologic processes include: genetic abnormalities, hemodynamically-induced
      changes associated to shear stress, endothelial abnormalities, dysfunction of
      potassium channels, and extracellular matrix alterations. Other processes such as
      -in situ--thrombosis, angiogenesis, and cellular apoptosis may also be involved.
      The medical management of this condition has improved. The role of phlebotomy and
      long-term oxygen therapy is now better defined. Furthermore, as a result of a
      better knowledge in pathobiology, new and promising forms of pharmacological
      treatment have appeared, including prostacyclin analogs, such as Epoprostenol
      (Flolan) for continuous intravenous use and Trepostinil sodium (Remodulin) for
      continuous subcutaneous administration.

PMID- 12001848
TI  - [Heart insufficiency in aortic valve disease: prognosis and treatment].
AB  - The purpose of this paper is to review the mortality rate in patients with aortic
      stenosis, and the special subgroup of this pathology associated with left
      ventricular dysfunction and clinical data of heart failure. The left ventricular
      dysfunction is recognized by low aortic gradients, and differentiation must be
      made between reversible ventricular dysfunction, in which case the optimal
      treatment is surgery, and irreversible ventricular disfunction, since in these
      cases surgical treatment will have excessively high mortality rates and no
      benefit.

PMID- 12001849
TI  - [The heart in hypertension. Cardiac protection and cardiac repair].
AB  - Studies performed in the last five years have led to the knowledge of new
      mechanisms by which the hypertensive process produces hypertrophy and cardiac
      fibrosis, at the same time, favoring development of the atheroesclerotic plaque.
      The Renin-Angiotensin-Aldosterone axis is relevant by involved in the
      physiopathology of these alterations, not only by producing hyperplasia and
      hypertrophy of vascular smooth muscle cells or by increasing protein and DNA
      syntheses, mediated by Angiotensin II (by itself a potent Growth factor) but also
      through inflammatory processes exerted upon the vascular smooth muscle cells.
      These alterations (hypertrophy, fibrosis, inflammation, and destabilization of
      the atherosclerotic plaque) can now be counteracted by blocking the Angiotensin
      Converting enzyme or its AT1 receptors with the consequent improvement in
      ventricular diastolic functions.

PMID- 12001850
TI  - [Models of experimental hypertension].
AB  - Many different animal models have been used to study hypertension, and diverse
      species have been chosen. Probably the most commonly used is the rat, not only on
      account of its comparatively low maintenance cost and easy handling, but because
      the pathology developed in these animals is quite similar to that observed in
      humans. Some results obtained from experiments done at this Institute with some
      of these models are discussed in this paper.

PMID- 12001851
TI  - [The future of PET in cardiology].
AB  - Positron emission tomography (PET) is an intrinsically quantitative method that
      provides an approach for the clinical cardiologist and cardiovascular researchers
      to evaluate the heart noninvasively. The ability to label biomolecules with
      positron-emiting radioisotopes, without disturbing their physiological
      properties, offers the opportunity to prove and quantify coronary blood flow,
      myocardial metabolism, and the alterations that occur with disease states.
      However, the major drawback prohibiting implementation of PET imaging in clinical
      routine is the limited availability of PET equipment and its greater cost per
      study. In order to enhance cost savings and resource efficiency in clinical
      practice, PET studies should be limited to those patients with equivocal studies
      by other imaging modalities or to define areas of potential viability and improve
      decisions for recommending coronary bypass grafting or cardiac transplantation.
      The combined data of multiple investigators suggest that 18-FDG-SPECT imaging may
      become the protocol of choice for determining myocardial viability because of its
      increased availability and cost-effectiveness as compared to PET.

PMID- 12001852
TI  - [Role of the echocardiogram in adults with congenital cardiopathy].
AB  - Advances in cardiac surgery, intensive care and non-invasive diagnostic methods
      in congenital heart diseases have allowed ford a high percentage of these
      patients to arrive to adult hood. Initial presentation of this type of anomalies
      in adult life is now uncommon. Most of these lesions are not arribe complex and
      easily acknowledged, but occasionally complex defects that represent a challenge
      for the diagnostic and treatment options. The handling of this groups of patients
      requires detailed information of the cardiac anatomy and cardiovascular
      pathophysiology. Transthoracic echocardiography (TEE) is a widely used method
      considered the initial method of choice. The transesophageal echocardiography
      (ETE) in combination with pulsed and continuous wave Doppler and color flow
      mapping provide high image resolution, in real time, of the cardiac structures to
      establish the diagnosis and hemodynamic repercussion, offering besides an
      important support during interventional cardiac catheterization procedures and
      monitoring during surgical procedures. To perform and interpret the studies of
      congenital heart disease, it must be acknowledged that this is a highly
      specialized technique that requires in depth knowledge of the spatial cardiac
      anatomy and pathology of the lesions, as well as the understanding of the
      different options of treatment and complications. Recently a it three-dimensional
      reconstruction of cardiac ultrasound image has which permits the spatial
      recognition of the intracardiac anatomy and provides additional information for
      the understanding of the congenital heart disease.

PMID- 12001853
TI  - [Therapeutic catheterization in adults with congenital cardiopathy].
AB  - We report our results with therapeutic cardiac catheterization in adult patients
      with four of the most frequent congenital heart diseases. 1) Valvular pulmonary
      stenosis. We treated 20 patients older than 15 years of age and we concluded that
      anatomy of the valve is the most important variable related to immediate and long
      term results. 2) Aortic coarctation. In a group of 54 patients, 32 treated with
      angioplasty alone and 22 with stent, we concluded that the main determinant for a
      good long-term result is the residual gradient, which is related to the
      coarctation anatomy and the use of stent. 3) Patent ductus arteriosus. In 17
      adult patients, the ductus was occluded with coils in 5 and with the Amplatzer
      duct occluder in 12 with complete occlusion of the ductus in all cases followed
      for a mean period of 18 months and without complications. 4) Atrial septal
      defect. We treated 39 adult patients using the Amplatzer septal occluder with
      good results.

PMID- 12001854
TI  - [Ambulatory monitoring of arterial hypertension].
AB  - Systemic high blood pressure is a very frequent disease. One characteristic is
      its daily continuous variability. Ambulatory monitoring of blood pressure has
      some advantages over the clinical blood pressure reading at the doctor's office.
      It is more precise, reliable, records the pressure at night and during sleep,
      avoids "white coat" phenomenon, among other things. This does not mean that blood
      pressure should not be taken during the regular medical visits. If there is any
      doubt of the presence of hypertension, blood pressure should be taken 3-4 times
      par day during several days to ensure the diagnosis, because one high blood
      pressure reading does not establish the diagnosis of systemic hypertension.

PMID- 12001855
TI  - [Nursing participation in the coordination of organ transplants].
AB  - The significant growth and development in the field of transplantation has
      enabled people who suffer from a terminal disease to live longer and with a
      better quality of life. However, there is still a lack of sensibility for
      organ/tissue donation in our society. The list of people waiting for an organ
      grows every day, but not the list of donors. The truth is that without a donor,
      there is no transplant. Nurses play an important role in this process. They have
      the knowledge, clinical experience, and management skills to collaborate,
      organize, and implement specific activities in the transplant process. These
      activities will be explained in this article. Transplant Coordinator Nurses have
      the potential to develop their skills in different areas of nursing: patient
      care, research, teaching and humanism.

PMID- 12001856
TI  - [Nurses' participation in heart rehabilitation].
AB  - The goal of cardiac rehabilitation is to incorporate patients with heart disease
      into their physical and social activities in such conditions that will allow them
      to lead a normal life "as good as possible". Their psychological needs have to be
      addressed, since these patients on leaving the hospital are anxious and afraid of
      the their future. The rehabilitation team must train the patients until they
      reach with success phase II of the heart rehabilitation program. The nurse plays
      and important role since she/he is the main mentor during phase II. At the
      cardiac rehabilitation service of the Instituto Nacional de Cardiologia "Ignacio
      Chavez", we worked during May, June, July of last year with 45 patients in phase
      II; of these, 84% were men, most between 60 and 79 years of age (60%). The most
      frequent diagnoses were ischemic cardiopathy (71%) and arterial hypertension
      (64%). The most frequent medical-surgical treatments were: thrombolytic therapy,
      angioplasty, and placement of stents and aortic-coronary ducts in 48%.
      Stratification was of high risk in 62.2%.

PMID- 12001857
TI  - [Treatment of systemic arterial hypertension].
AB  - The World Health Organization (WHO) and several other international committees on
      the study of hypertension define that a patient with blood pressure between
      140/90-150/95 mmHg must be treated. In the first stage of hypertension it is
      possible to modify it with life style changes, but if high blood pressure
      persists, then drug therapy must be evaluated carefully. Drug therapy management
      is individualized and based upon age, race, previous history of hypertension, and
      risks for target systemic organs. At the National Institute of Cardiology
      "Ignacio Chavez" in Mexico City there is a wide experience with drugs of several
      groups, and treatment is chosen to give the patient the greatest advantage and
      quality of life. Nursing requires a clear and precise knowledge of drug therapy
      in hypertension, as well as the understanding of its physiopathology to support
      in an effective way each one of the interventions. Through the Nursing process,
      Nurses direct their actions not only to the correct administration of drugs, but
      also, based on the patients background, to orient, inform, and educate the
      patient about disease to achieve a strict drug therapy compliance, in order to
      reach the main goal of the process, the which is the best quality of life
      possible.

PMID- 12001858
TI  - [Nursing process in heart failure].
AB  - The nursing process is a method that guides nursing actions, which are necessary
      to foster a fast recovery in patients. This process may be developed in a
      holistic way based on several nursing models, according to the needs of the
      patient coursing with some kind of cardiac failure. The objective of this
      investigation was to collect epidemiological and clinical data, as well as on
      diagnostic and therapeutic actions for cardiac failure. We also describe the
      physiopathology of the diseases to inform the nursing staff on the relevance of
      the nursing process within hospitals and how it will result in better care,
      decreasing time and costs of hospitalization and increasing benefits, which are
      the goals proposed.

PMID- 12001859
TI  - [Kidney transplantation].
AB  - The first renal transplant with little success was performed in 1933. It was not
      until 1947, in Boston (USA), when a cadaveric kidney was transplanted into a
      female patient with septic shock, renewing natural diuresis in two months. In
      1950, different European and American medical teams had already proceeded with
      renal transplants in humans from cadaver donors with positive results, followed
      by an absolute success with the first renal transplant in univitelline twins in
      1954. In 1961, its use with immunosuppressive therapy was approved. In Mexico, in
      1968, the first renal transplant with a six-year survival was achieved. Four
      years later, the first renal transplant with satisfactory results is performed at
      the National Institute of Cardiology. Along the 35 years of activity of the renal
      transplant program, 516 renal transplants from alive donors and 19 from cadaveric
      donors have been performed with an average of eight-year survival. Nurses
      participate actively from the moment at which the transplant patient and the
      donor are admitted to the hospital, as well as during, the transplant itself, the
      recovery period, and by providing support and information to both the patients
      and their families.

PMID- 12001860
TI  - [Hypothyroidism protects the myocardium against ischemia-reperfusion injury].
AB  - This work describes experimental results indicating that mitochondria from
      hypothyroid rats are resistant to suffer membrane permeability transition as
      induced by matrix calcium accumulation. It is also shown that hypothyroidism
      provides resistance to myocardial reperfusion injury, after a period of 5 min
      ischemia. It is concluded that the protection is due to a low expression of
      mitochondrial proteins, as well as to a lack in cardiolipin as constituent of the
      lipid bilayer of the inner mitochondrial membrane.

PMID- 12001861
TI  - [Nursing process in advanced cardiopulmonary resuscitation].
AB  - The process male nurse is a systematic and organized method to offer effective
      and efficient cares guided to the achievement of solving real problems of health,
      reducing the incidence and the duration. It is organized and systematic for that
      consists of five sequential and interrelated steps: Valuation, diagnostic,
      planning, execution and evaluation, in which are carried out interrelated
      actions, thought to maximize the long term results. The nurse process is based on
      the notion that the success of the cares is measured by the degree of
      effectiveness and the degree of satisfaction and the patient's progress. Applying
      this method in the Advanced Cardiac Live Support (ACLS) the identification of a
      cardiovascular or cardiopulmonary urgency was achieved that implies advanced
      treatment of the air road, defibrillation and appropriate medications to the
      circumstances. The ACLS challenges the nurses in charge from the patient's
      attention to make decisions quick low pressure and in dramatic scenes. Reason why
      it develops the flowing process male nurse in the advanced cardiopulmonary
      reanimation due to the incidence of these events in the National Institute of
      Cardiology Ignacio Chavez, which should guarantee the benefit of services in
      basic and advanced cardiopulmonary reanimation for personal with a high formation
      level in all the units of intensive cares and services of hospitalization in
      integrated form and stratified this way to avoid that it progresses to situations
      that cause the death or leave irreversible sequels since in the central nervous
      system the time it is a factor critical for the treatment of this events.

PMID- 12001862
TI  - [Cardiopulmonary diversion in minimally invasive heart surgery].
AB  - Cardiac surgery has evolved greatly in the last pears. New techniques for the
      treatment of cardiac patients, such as minimally invasive heart surgery, off-pump
      coronary surgery, limited or port access surgery, video-assisted and robotic
      cardiac surgery have been developed. Technology provides new instruments, such as
      heart stabilizers for off-pump coronary surgery, ventricular support devices or
      direct coronary bypass perfusion systems, all of them with the main goal of
      maintaining the patient's hemodynamics. Minimally invasive heart surgery
      contributes to a faster recovery and less suffering, and decreases costs. The
      perfusionist is involved in all these new techniques, the future is a challenge,
      he she must learn to use all these new devices without forgetting the human sede
      of his her specialty.

PMID- 12001863
TI  - [Nursing care of patients with acute pulmonary edema].
AB  - Nursing care of patients with acute lung edema is vital, as well as their timely
      diagnosis and treatment. The nurse, through the corresponding evaluation,
      diagnoses and accelerates the treatment avoiding death of the patient by
      detecting the event appropriately and providing treatment to stabilize the
      patient. The care of a multidisciplinary medical team is required to solve this
      emergency that can be of cardiogenic or non-cardiogenic origin. Injury of the
      capillary endothelium and blockade of lymphatic vessels are its main causes. In
      acute lung edema occurs and accumulation of serous liquid in the alveoli of the
      lung, which produces severe hypoxia. Nurse interventions, in order of priorities,
      are aimed primarily at resolving, the oxygenation needs of the patient.

PMID- 12001864
TI  - [Bioethics and nursing praxis].
AB  - Bioethics is a discipline that has gained great relevance in today's world
      Changes in health care, advances in technology and science are giving hope to
      life, however they are also causing ethic conflicts. Patients are at risk of
      loosing their own right to live or die. Healthcare professionals are meant to
      deliver care, but also to protect the rights and the quality of life of the
      patients. As more and more people have recognized the importance of bioethics,
      ethic committees have sprung up in many healthcare settings. Continuing education
      programs on ethical principles and ethical decision/making models are critical.
      Nurses play an important role, they bridge the gap between the needs of
      individual patients and the healthcare system. They have a very close contact
      with the patients. Nurses have the ability to recognize moral problems as actual
      or potential conflicts in rights, duties or principles, and to take appropriate
      action to resolve the ethical issue.

PMID- 12001865
TI  - [Use of platelet antiaggregating agents in acute coronary syndromes].
AB  - Nowadays, it is known that platelets are the main agents involved in the
      pathogenesis of acute coronary syndromes, and the fact that aspirin is a weak
      antiplatelet agent has led to an intensive research in antiplatelet drugs in the
      last years. The medical literature from the last decade contains many studies on
      the use of platelet IIb/IIIa receptor blockers in different clinical settings.
      Agents that block the IIb/IIIa platelet receptor have shown to be useful in
      improving prognosis of patients with acute coronary syndromes (ACS), especially
      in those studies of percutaneous coronary revascularization procedures. However,
      their potential risk of causing bleeding and high cost have prevented applied
      universal and routine application. There are some aspects, such as correct
      dosage, optimal duration of treatment, and direct comparison of the efficacy of
      different types of IIb/IIIa blockers, that not have not been resolved yet. On the
      other hand, oral IIb/IIIa antagonists have not exceeded the efficacy of aspirin.
      Finally, it is necessary to identify those patients that will obtain the most
      benefit from this treatment to avoid unnecessary risks and costs. Therefore, it
      is very important, for the nurse to have the necessary knowledge on the
      therapeutic effect and use of this antiplatelets therapy, to be able to identify
      in time any complication that night increase the risk and in danger the patient's
      life.

PMID- 12001866
TI  - [Nursing care in systemic arterial hypertension].
AB  - The analysis shown below was made in order to bring out the importance of the
      nursery professional behavior on its three levels related to the Systemic
      Arterial Hypertension, which is considered as the main factor for cardiovascular,
      brain vascular and renal sufferings because it's an unknown affectation for most
      of the people who suffers from, it. This is why is for the professional nurse to
      have all the knowledge that would let him develop correctly a diagnostic which
      may help to improve the service they provide, in order to promote the public
      weal, the timely disease detection, the cares needed and the supervision of
      treatments. The professional nurse will have to be able to create specific
      conditions in every patient, so they can change their life styles habits
      appropriately. This is how society will be involved on issues just as prevention,
      control and eradication of this particular disease and also these actions will
      help to minimize the mortality index, the families welfare and particularly the
      people's quality life styles.

PMID- 12001867
TI  - [Congenital cardiopathies and syndromes in adults].
AB  - Among congenital defects the most common are the congenital heart defects, which
      constitute a heterogeneous group with a multifactor etiology. A single gene
      mutation has been identified in some of them, such as in of Williams's syndrome,
      or they can be due to teratogenic agents. The advance in diagnosis and treatment
      of congenital heart defects has become very important because mortality has
      diminished and patients live longer and better, reaching adult hood. Molecular
      biology offers now opportunities understand the cause of many genetic diseases
      thanks to molecular studies of chromosomes. Conotruncal malformations are known
      to be caused by a microdeletion in chromosome 22(22q11), this mutation is also
      responsible for the DiGeorge and cardiovelofacial syndromes, the most relevant
      aspects are: congenital heart disease, which is present in 75% of the cases, the
      leading disorder is Fallot's tetralogy with pulmonary atresia, in second place is
      interruption of the aortic arch type B, followed by common truncus arteriosus.
      These patients have other phenotypic features, such as high palate, speech
      problems, malimplantation of ears, and protuberant nose tip, among others.
      Diagnosis is made with the FISH (fluorescent in situ hybridization) test that
      shows a microdeletion in chromosome 22 at the 11.2 region. Another syndrome that
      has received great attention is the Williams-Beuren syndrome, which courses with
      mental retardation, hypercalcemia, characteristic facies, and supravalvular
      aortic and pulmonary stenosis. To day, it is known that its cause is a deletion
      in chromosome 7(7q11.23), which affects elastin region, in consequence, affecting
      the vessels.

PMID- 12001868
TI  - [Current status of pharmacologic treatment of arrhythmia].
AB  - Arrhythmias result from alterations in the electrophysiological properties of the
      heart: excitability, automatism, conduction, refractory period, and
      repolarization. These properties depend on the cellular membrane voltage. This
      voltage is a consequence of macromolecular tunnels permitting the flow of
      electrical charged particles and the action of the electrogenic pumps against
      electrochemical gradients. The voltage alterations in the membrane give rise to
      arrhythmogenic mechanisms resulting of automatism alterations or disorders in
      conduction, producing re-entry or circus movement. The medical treatment must be
      based on a correct integral diagnosis, knowledge of the trigger and maintenance
      mechanisms of the arrhythmia as well as on the pharmacology of the drug. The
      antiarrhythmic drug classifications are useful for didactic purposes but may be
      of little use in medical practice. In supraventricular arrhythmias, the
      mechanisms are known and can be identified; the re-entry pathways are also known
      and the electrophysiological mechanisms are normal, therefore the response to the
      drugs is predictable. In contrast, in ventricular arrhythmias, the mechanisms are
      variable, the circuits are very difficult to identify and involve healthy and
      sick tissues. The therapeutic indication is very difficult and incorrect in many
      occasions. It is possible that, in the future, the study of hereditary
      arrhythmias could be the basis for a better understanding of these problems.

PMID- 12001869
TI  - [Sudden death. Role of the electrophysiologic study].
AB  - At present, sudden death is considered a major health problem, DeBoer in 1935,
      recognized the clinical importance of ventricular fibrillation as the cause of
      sudden cardiac death. Sudden death due to cardiovascular problems has been
      established as one of the main causes of death in the developed countries and in
      developing countries as ours, where the deaths caused by cardiovascular diseases
      represent 15% of the total, exceeding other causes of death. The frequency of
      sudden death in our country is unknown, but more frequently we hear about cases
      of patients that have been reanimated for cardiac arrest; in the United States of
      America the frequency has been estimated between 400,000 at 500,000 per year
      although, recently, 250,000 at 300,000 events are being mentioned. It is
      convenient to comment that the causal arrhythmias are diverse and may vary
      depending on the underlying disease, although, generally, it can be pointed out
      that 80% of them are due to tachyarrhythmias. It's important to point out that
      there is a strong relationship between left ventricular dysfunction, the
      frequency of ventricular arrhythmias, and fatal cardiac events due to cardiac
      rhythm disturbances. The recommendations for electrophysiological studies are: 1)
      patients surviving cardiac arrest, occurring without evidence of an acute Q-wave
      myocardial infarction and 2) patients surviving cardiac arrest occurring more
      than 48 hours after the acute phase of myocardial infarction in the absence of a
      recurrent ischemic event.

PMID- 12001870
TI  - [Heart failure and pure mitral failure. Prognostic impact and its best
      treatment].
AB  - The most common etiologies for mitral regurgitation (MR) include mitral valve
      prolapse syndrome, coronary artery disease, infective endocarditis, rheumatic
      heart disease, collagen vascular disease, and, recently, anoretic drugs have also
      been reported to cause MR. In chronic severe MR, forward cardiac output is
      maintained for the development of afterload reduction with increase in
      compensatory left ventricular (LV) end-diastolic volume and LV ejection fraction.
      It is well established that some patients with asymptomatic mitral regurgitation
      develop irreversible contractile dysfunction of the LV, which is often masked by
      the afterload-reducing effect of the regurgitant flow; cardiologist have to use
      some variables, like LV chamber elastance, LV End-Systolic dimensions and
      volumes, left atrial area combined with ejection fraction, in their clinical
      evaluations tube able to predict surgery mortality. Careful and periodic
      evaluation of left ventricular function and size is essential to optimize the
      timing of surgical intervention in these patients. After symptoms occur, outcome
      is improved with surgical interventions compared to medical therapy, with a
      reported survival of only 45% at 5 years without surgical intervention.
      Vasodilators, diuretics, and recently, angiotensin receptor antagonists have been
      used in MR medical therapy. Long-term carvedilol therapy in patients with chronic
      heart failure may prevent or partially reverse progressive left ventricular
      dilatation. Concomitant by, it has been associated with recovery of diastolic
      reserve and a decrease in mitral regurgitation.

PMID- 12001871
TI  - [Heart failure in acute myocardial infarction].
AB  - Heart failure during the immediate period of an acute myocardial infarction
      constitutes a major insult to this pathology; since, once installed, it is
      associate to ventricular dysfunction and expansion of the left ventricle. It can
      appear either early or delayed. Subsequent to the acute insult, the myocardium is
      subjected to diverse changes in its anatomical conformation and to diastolic and
      systolic alterations, which will affect the hemodynamic constants of the patient.
      Changes in the parietal ventricular architecture as well as at the neurohumoral
      level will also occur. The clinical signs of heart failure are: dyspnea, pallor,
      tachycardia, diaphoresis, cold skin, oliguria, somnolence, and gallop, which can
      be observed at the very beginning of the coronary occlusion. Its clinical
      identification, through in-hospital studies supported by adequate hemodynamic
      monitoring, is of utter relevance since it will lead to appropriate and fast
      treatment. The groups of patients with acute myocardial infarction with high risk
      for the development of cardiac failure are: patients with extensive Q wave
      infarction, diabetic, patients over 65 years of age, and those with a history of
      previous myocardial infarction(s). The cornerstone of treatment must be focused
      on reducing the myocardial ischemia, which can be achieved through the use of
      modern therapeutics and, given the case, pharmacological agents, coronary
      intervention procedures, or cardiac surgery must be taken into account. At
      present it is known that angiotensin converting enzyme inhibitors, betablockers,
      inotropics, are useful to improve ventricular function in patients with acute
      myocardial infarction.

PMID- 12001872
TI  - [Impact of antihypertensive treatment on target organs].
AB  - We review the mechanisms by which arterial hypertension induces target organs
      damage, particularly the heart, kidney, and vascular endothelium, which is
      manifested as ventricular hypertrophy, proteinuria, and renal failure and
      endothelial dysfunction. Furthermore, the effect of antihypertensive treatment in
      these situations is analyzed. Experimental and clinical studies show that
      angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II
      receptor antagonist drugs are more efficient than other antihypertensive
      treatments in the reversal of left ventricular hypertrophy and proteinuria, in
      delaying kidney damage and improving of endothelial function.

PMID- 12001873
TI  - [Treatment of intrastent restenosis].
AB  - The use of stents has significantly reduced post PTCA restenosis rates. However,
      even with optimal stenting the rate of instant restenosis (ISR) is 8-15%. Thus,
      the extended use of stents (> or = 85% of angioplasty procedures) has made ISR a
      growing problem. We review the current interventional approach for treating ISR,
      where the strategy is dictated by the extent of the restenotic plaque. For focal
      lesions, redilation with balloon is the therapy of choice. For diffuse lesions,
      the Cutting Balloon offers good angiographic results with acceptable recurrence
      rates; in some selected cases, plaque removal can be helpful with a tendency for
      better results with rotablation. In centers where brachitherapy is available,
      this is considered the preferred approach for diffuse ISR. In all ISR cases, the
      alternatives of continuing medical therapy or surgical therapy should also be
      considered in the decision-making process.

PMID- 12001874
TI  - [Progress in the treatment of diabetic patients with ischemic cardiopathy].
AB  - Among the risk factors for ischemic cardiopathy none influences more long-term
      restenosis and mortality as diabetes mellitus. Diabetes mellitus is ranked third
      as cause of death; 65 to 85% of these patients die due to cardiovascular disease.
      The use of coronary stents associated to glycoprotein IIb/IIIa inhibitors has
      proven to be superior to stents alone or PTCA in the treatment of ischemic
      cardiopathy in diabetic patients. Despite these improved results, restenosis
      rates remain higher as compared to non-diabetic patients. Intracoronary radiation
      has been shown decrease restenosis and repeat target lesion revascularizations in
      diabetic patients with intra-stent restenosis. In order to decrease restenosis in
      diabetic patients, stents coated with site-specific pharmacological and molecular
      approaches may prove useful in suppressing hyperplasia of the intimal and
      preventing restenosis. Coronary artery bypass grafting seems to be the best
      option for diabetic patients with multiple coronary artery disease, especially if
      they have proximal left anterior descending artery estenosis, complex lesions to
      be approached by angioplasty, previous myocardial infarction, three vessel
      disease, or impaired left ventricular function. In spite of improvements in the
      treatment of diabetic patients with coronary artery disease, restenosis and
      mortality rates continue to be higher as compared to non-diabetic patients;
      therefore, new strategies are required.

PMID- 12001875
TI  - [2001. Commemoration of the XXV Anniversary of the new National Institute of
      Cardiology "Ignacio Chavez" of Mexico].

PMID- 12001876
TI  - [Interventional treatment of lesions of unprotected left main coronary disease].
AB  - The percutaneous treatment of unprotected left main coronary artery disease began
      with the first angioplasties, but was discarded soon because of its high
      mortality. With the new techniques of percutaneous interventions, the more
      frequent use of the stent and antithrombotic medication, acute angiographic
      alterations can be treated with success in most patients. Hospital mortality is
      related to the baseline status, being worse for patients with acute myocardial
      infarction or at high surgical risk. The restenosis rate is related to the
      location of the lesion and the reference size of the vessel. Nowadays, the
      percutaneous treatment for the unprotected left main coronary artery disease is
      no longer an absolute contraindication for certain patients, although there is
      still not enough scientific evidence for its use as standard treatment for all of
      them.

PMID- 12001877
TI  - [Brugada's syndrome].
AB  - The Brugada syndrome is an arrhythmic syndrome characterized by a right bundle
      branch block pattern and an segment elevation in the right precordial leads of
      the electrocardiogram, in conjunction with a high incidence of sudden death
      secondary to ventricular tachyarrhythmias. No evidence of structural heart
      disease is noted during diagnostic evaluation of these patients. The prognosis is
      poor with up to a 10 per year mortality. Antiarrhythmic drugs have no benefit in
      prolonging survival. The treatment of choice is the insertion of an implantable
      cardioverter defibrillator.

PMID- 12001878
TI  - [Current status of implantable cardioverter defibrillator].
AB  - Clinical trials have established the superiority of the implantable cardioverter
      defibrillator (ICD) over antiarrhythmic drug therapy in survivors of sudden
      cardiac arrest and in high risk patients with coronary artery disease. The ICD
      has evolved to overcome the limitation of earlier devices that required
      thoracotomy for implantation and inadequate therapies. At present, it is
      implanted in a similar manner to cardiac pacemakers and incorporates
      discrimination algorithms to prevent inappropriate therapy. Managing the patients
      with an ICD requires an understanding of the multiprogrammable features of modern
      devices. The cost-effectiveness of ICD therapy appears favorable, given the
      marked survival benefit seen in randomized trials relative to antiarrhythmic drug
      treatment. A goal of newer-generation ICD devices is to avoid intervention. Such
      programmable therapies may include pacing to avoid long short coupling,
      intermittent antiarrhythmic drug infusion, or multisite pacing to improve
      hemodynamics. Further advances in device technology will undoubtedly expand the
      role of the ICD in the primary and secondary prevention of sudden cardiac arrest.

PMID- 12001879
TI  - [Nuclear cardiology in myocardial viability].
AB  - The goal of myocardial viability assessment is to differentiate, prospectively,
      patients with potentially reversible from irreversible left ventricular
      dysfunction. Ideally, this information should be used to guide therapeutic
      decisions for revascularization. Therapeutic interventions that improve non
      functioning but viable myocardial regions may improve significantly global left
      ventricular function as well as impact left ventricular dysfunction, in which
      revascularization entails high perioperative morbidity and mortality. Accurate
      assessment of myocardial viability may result in more appropriate utilization of
      resources and enhance efficiency in health care delivery. Myocardial viability
      can be valorated with perfusion images using dual method or tallium reinjection,
      isotopic ventriculography, Gated SPECT with dobutamine stress or cardiac
      metabolism with PET.

PMID- 12001880
TI  - [Gene therapy in cardiology].
AB  - The modification of genetic material of living cells for therapeutic purposes
      have been regarded by many as an unrealized promise. However, recent successful
      achievements in the field have contributed to vanish this perception and have
      reopened the possibility to use gene therapy as a medical intervention in humans.
      In the case of cardiovascular diseases, and despite its high prevalence, the
      number of approved human gene therapy protocols has remained low. This may be
      due, at least in part, to the availability of effective alternative therapies for
      some of the most common vasculopathies. However, recent advances in the
      understanding of the genetic and molecular bases of the cardiovascular system
      have opened the possibility to introduce gene therapy in the management of a
      great variety of cardiovascular disorders. The purpose of this communication is
      to briefly summarize the progress in this area.

PMID- 12001881
TI  - [Rational treatment of hypertensive crises].
AB  - The Hypertensive Crisis can be divided into Emergencies and Urgencies.
      Hypertension may be unknown at presentation. The Emergencies have acute or
      ongoing end-organ damage (neurological, renal or cardiovascular). It is crucial
      to recognize one from another already at the emergency room evaluation. There is
      no arbitrary level of blood pressure separating hypertensive emergencies and
      urgencies. Ideally, this patients must be treated in an intensive care unit. The
      level to which the blood pressure should be lowered and the election of the
      treatment, parenteral versus oral, depends on the patient's general condition and
      should be individualized. The general recommendation is to reduce the mean
      arterial pressure gradually in the first 48 hours by no more than 20 percent or
      to a diastolic blood pressure not lower than 100 mmHg. A relatively asymptomatic
      patient, even with high diastolic lectures does not need to be treated with
      parenteral drugs. The patient should be evaluated for possible factors that may
      have contributed to the high of blood pressure and the progression of
      hypertension.

PMID- 12001882
TI  - Heart rate variability biofeedback as a method for assessing baroreflex function:
      a preliminary study of resonance in the cardiovascular system.
AB  - This study describes the use of a biofeedback method for the noninvasive study of
      baroreflex mechanisms. Five previously untrained healthy male participants
      learned to control oscillations in heart rate using biofeedback training to
      modify their heart rate variability at specific frequencies. They were instructed
      to match computer-generated sinusoidal oscillations with oscillations in heart
      rate at seven frequencies within the range of 0.01-0.14 Hz. All participants
      successfully produced high-amplitude target-frequency oscillations in both heart
      rate and blood pressure. Stable and predictable transfer functions between heart
      rate and blood pressure were obtained in all participants. The highest
      oscillation amplitudes were produced in the range of 0.055-0.11 Hz for heart rate
      and 0.02-0.055 Hz for blood pressure. Transfer functions were calculated among
      sinusoidal oscillations in the target stimuli, heart rate, blood pressure, and
      respiration for frequencies at which subjects received training. High and low
      target-frequency oscillation amplitudes at specific frequencies could be
      explained by resonance among various oscillatory processes in the cardiovascular
      system. The exact resonant frequencies differed among individuals. Changes in
      heart rate oscillations could not be completely explained by changes in
      breathing. The biofeedback method also allowed us to quantity characteristics of
      inertia, delay, and speed sensitivity in baroreflex system. We discuss the
      implications of these findings for using heart rate variability biofeedback as an
      aid in diagnosing various autonomic and cardiovascular system disorders and as a
      method for treating these disorders.

PMID- 12001883
TI  - Biofeedback and hypertension: a deja vu experience. Comments on Yucha's "Problems
      inherent in assessing biofeedback efficacy studies".
AB  - The author makes several comments and observations on Yucha's recent paper on
      biofeedback treatment of hypertension (C. B. Yucha, 2001). In particular, he
      highlights the need for replicability of biofeedback treatment effects to move
      the field forward.

PMID- 12001884
TI  - Muscle tension and physiologic hyperarousal, performance, and state affectivity:
      assessing the independence of effects in frequent headache and depression.
AB  - Anxiety, depression, and frequent headache are closely associated. The
      comorbidity may be due to selection bias (such as inherent in treatment seeking),
      shared environmental or genetic factors, or a common underlying process. In this
      study, comorbidity is considered an alternative explanation for correlates of
      frequent headache found in earlier work. This study addressed whether EMG,
      peripheral temperature, performance measures, and measures of affect were
      independently attributable to depression or headache proneness, after control of
      trait anxiety. Headache state was evaluated in parallel analysis. Seventy-two
      participants, comprising four groups, were tested: depressed/headache-prone
      depressed/headache-resistant, not depressed/headache-prone, and not
      depressed/headache-resistant. Participants completed a performance task that
      allowed assessment of ambition and performance accuracy while measures of affect,
      headache state, EMG, and peripheral temperature were obtained. Headache
      proneness, independently of depression and trait anxiety, was related to
      heightened EMG. Depression was related to EMG, ambition, and performance accuracy
      independently of headache proneness and trait anxiety. Headache state was
      associated only with negative affect, independently of depression and anxiety.
      These results suggest that headache states during assessment, as well as comorbid
      depression and anxiety, are not primarily responsible for the heightened EMG
      found in headache-prone individuals. Negative affect often reported in the
      headache prone, however, may be due to concommitant anxiety. Other analyses
      address a variety of issues surrounding distinctions among these variables raised
      in previous research.

PMID- 12001885
TI  - Autogenic training: a meta-analysis of clinical outcome studies.
AB  - Autogenic training (AT) is a self-relaxation procedure by which a
      psychophysiological determined relaxation response is elicited. A meta-analysis
      was performed to evaluate the clinical effectiveness of AT. Seventy-three
      controlled outcome studies were found (published 1952-99). Sixty studies (35
      randomized controlled trials [RCT]) qualified for inclusion in the meta-analysis.
      Medium-to-large effect sizes (ES) occurred for pre-post comparisons of disease
      specific AT-effects, with the RCTs showing larger ES. When AT was compared to
      real control conditions, medium ES were found. Comparisons of AT versus other
      psychological treatment mostly resulted in no effects or small negative ES. This
      pattern of results was stable at follow-up. Unspecific AT-effects (i.e., effects
      on mood, cognitive performance, quality of life, and physiological variables)
      tended to be even larger than main effects. Separate meta-analyses for different
      disorders revealed a significant reduction of the heterogeneity of ES. Positive
      effects (medium range) of AT and of AT versus control in the meta-analysis of at
      least 3 studies were found for tension headache/migraine, mild-to-moderate
      essential hypertension, coronary heart disease, asthma bronchiale, somatoform
      pain disorder (unspecified type), Raynaud's disease, anxiety disorders, mild-to
      moderate depression/dysthymia, and functional sleep disorders.

PMID- 12001886
TI  - Problems inherent in assessing biofeedback efficacy studies.
AB  - This paper discusses some of the problems involved in drawing conclusions across
      studies about the efficacy of biofeedback. It focuses on biofeedback for the
      treatment of hypertension, but the same difficulties arise when considering the
      effect of biofeedback in other disorders. Large multicenter studies using the
      same inclusion and exclusion criteria, biofeedback protocol, and methodology are
      badly needed if biofeedback practitioners are ever going to demonstrate the real
      effectiveness of biofeedback.

PMID- 12001887
TI  - Proceedings of the 4th Annual Meeting of Dermatology Forum for Basic Research and
      Treatment. June 17-18, 2000. Sapporo, Japan.

PMID- 12001889
TI  - Mosaic vessels shed cancer clues by the million.

PMID- 12001888
TI  - Careless talk costs confidence.

PMID- 12001890
TI  - Hyperbaric oxygen therapy.

PMID- 12001891
TI  - COPD is not a Cinderella disease.

PMID- 12001892
TI  - Taking the plunge.

PMID- 12001893
TI  - Less can be more.

PMID- 12001894
TI  - Community health council.

PMID- 12001895
TI  - Council on gerontological nursing.

PMID- 12001896
TI  - Maternal-child health council.

PMID- 12001897
TI  - Council of primary care nurse practitioners.

PMID- 12001898
TI  - Cabinet on professional and economic development.

PMID- 12001899
TI  - [Diagnostic criteria of meningomyeloradicular schistosomiasis mansoni].

PMID- 12001900
TI  - Managers & medicine: treatment guide.

PMID- 12001901
TI  - Physical activity counseling in primary care.

PMID- 12001902
TI  - Elevated lipoprotein(a) concentration is an independent risk factor of venous
      thromboembolism.

PMID- 12001903
TI  - Mixed warm and cold autoimmune hemolytic anemia: complete recovery after 2
      courses of rituximab treatment.

PMID- 12001904
TI  - Sperm protein 17 is not expressed on normal leukocytes.

PMID- 12001905
TI  - Severe neurotoxicity following arsenic therapy for acute promyelocytic leukemia:
      potentiation by thiamine deficiency.

PMID- 12001906
TI  - Successful double bone marrow and renal transplantation in a patient with Fanconi
      anemia.

PMID- 12001907
TI  - Cytomegalovirus infections in cancer patients receiving granulocyte transfusions.

PMID- 12001908
TI  - Expression of survival receptors in Hodgkin disease cell lines.

PMID- 12001909
TI  - Safety of early immunization against measles/mumps/rubella after bone marrow
      transplantation.

PMID- 12001910
TI  - Erythrocyte mean cell volume and genetic polymorphism of aldehyde dehydrogenase 2
      in alcohol drinkers.

PMID- 12001911
TI  - The role of interleukin-7 and interleukin-15 in cutaneous T-cell lymphoma.

PMID- 12001912
TI  - The "academic cartel": another pernicious weed in the field of academic medicine.

PMID- 12001913
TI  - Where are we going?

PMID- 12001914
TI  - ECG of the month. Functional discordance. Aberrant ventricular conduction.

PMID- 12001915
TI  - Posterior laryngeal cleft.
AB  - The posterior laryngeal cleft is a rare congenital anomaly which results from
      absence of fusion of the posterior cricoid lamina and possibly the
      tracheoesophageal septum. A high degree of suspicion is required for early
      diagnosis and repair to prevent significant morbidity and mortality from
      recurrent aspiration pneumonia. Minor clefts may be repaired endoscopically,
      whereas severe laryngotracheoesophageal clefts require a multidisciplinary
      approach with combined extrathoracic and intrathoracic repair. Associated
      congenital anomalies increase the mortality of the laryngeal clefts and may
      complicate the timing of surgical repair.

PMID- 12001916
TI  - Radiology case of the month. Does this patient have osteomyelitis?

PMID- 12001917
TI  - The Journal 100 years ago. June 1899.

PMID- 12001918
TI  - A report of congenital indifference to pain as diagnosed in infancy.
AB  - As physicians and nurses, we have a fundamental obligation to consider patient
      welfare above all else. The case presented demonstrates the depth of this
      obligation. Our patient, who was diagnosed during infancy with congenital
      indifference to pain, can neither feel nor perceive the meaning of pain.
      Congenital indifference to pain is a rare disorder, which is characterized by
      normal intelligence, development, and sensation despite an absence of pain
      perception. There is no cure and treatment difficulties are plentiful. Educating
      and maintaining an open, consistent relationship with the family and caregivers
      is essential to reduce the morbidity of this condition.

PMID- 12001919
TI  - Dengue fever risk and prevention for short-term group travelers to tropical
      regions.
AB  - The purpose of this study is to describe dengue fever infections in a group
      traveling from northern Louisiana to Mexico. Of 50 travelers in the group, three
      adolescents aged 15-16 developed febrile symptoms a few days after returning.
      Clinical diagnosis suggested dengue fever. Serum samples were obtained from the
      three adolescents and from 19 of the adults (age 18 and older) who were in the
      group. The samples were analyzed by the Centers for Disease Control using dengue
      IgM capture enzyme linked immunosorbant assay. Results confirmed the three
      symptomatic adolescents and five asymptomatic adults had been infected with the
      Flaviviridae virus that causes dengue. We conclude that since there is no vaccine
      to prevent dengue infections, travelers to high-risk areas should take steps to
      prevent infection and that clinicians encountering patients with febrile
      illnesses after travel to such regions should consider a diagnosis of dengue
      fever.

PMID- 12001920
TI  - Inventing the future of physicians and information technology: methods and
      results of the 1997 Lafayette Parish Medical Society Information Systems and
      Information Technology Project.
AB  - This paper challenges physicians to consider how to best invent a future in which
      they can personally leverage emerging information and communication technologies
      to maximize their effectiveness and efficiency as care givers. One Louisiana
      State Medical Society component medical society has already posed this challenge
      to its members. The paper describes the 1997 Lafayette Parish Medical Society
      Physicians' Information Systems and Information Project, conducted on behalf of
      the society by faculty of the Healthcare Administration MBA Program at the
      University of Southwestern Louisiana. Specific recommendations for application of
      health care information technologies by physicians and by health care
      institutions, based on findings and conclusions of the project, are highlighted.

PMID- 12001921
TI  - Frequency of HgbA1c testing as a measure of diabetes care in Louisiana.
AB  - The Frequency of HgbA1c Testing Project is a continuous quality improvement
      project designed to measure and improve the frequency of HgbA1c testing among
      Medicare diabetic patients in Louisiana. Louisiana Medicare Part B electronic
      claims data from June 1995 to December 1996 were used to construct diabetes
      quality of care type indicators. A total of 47,270 Medicare, Part B eligible, non
      HMO, diabetic patients were identified and studied. The statewide baseline
      results indicated that only 24% of the Medicare diabetic patients were covered by
      an HgbA1c test within 180 days from their last physician office visit. Twenty-one
      percent (21%) of practicing primary care physicians had none of their diabetic
      patients tested for HgbA1c within 180 days from the patient's last office visit.
      Overall, only 18% of all primary care physicians "seized" the opportunity to
      perform an HgbA1c test within this time frame. Twenty-two percent (22%) of
      Louisiana primary care physicians had never seized the opportunity to check for
      HgbA1c on eligible patients. Interventions and strategies are being implemented
      statewide in order to improve the low HgbA1c testing rates.

PMID- 12001922
TI  - More news from ICAAC.

PMID- 12001923
TI  - An HIV treatment the world may never see.

PMID- 12001924
TI  - Social Security beneficiaries returning to work.

PMID- 12001925
TI  - HCV/HIV co-infection II: sobriety and treatment.

PMID- 12001926
TI  - Positive empowerment.

PMID- 12001927
TI  - HIV activism, it's necessary.

PMID- 12001928
TI  - Why are there new cases of HIV?

PMID- 12001929
TI  - Honoring Konrad Bloch.

PMID- 12001931
TI  - [The National Pharmacopoeia and the therapeutic status of flora in Mexican
      biomedicine].
AB  - The paper analyses the transformation of the Mexican pharmacopoeia, focusing on
      the presence of medicinal plants. Reflecting diverse processes, editions of the
      pharmacopoeia show a progressive modification in its content and profile. A text
      written to shape a Mexican materia medica, recognising empirical knowledge by the
      inclusion of popularly used resources and involving clinicians as authors and
      recipients, was transformed into a mainly industrial publication with no clinical
      references. The origin and implications of this process are explored.

PMID- 12001932
TI  - [Medical pluralism revealed by private correspondence in XVIII century
      Catalonia].
AB  - This work constitutes an approach to the complex world of medical pluralism
      during the modern age. First, there is a review of the recent historiography
      concerned with recovering all the possible medical resources that existed and
      were offered to the patient. The complexity of this medical world are then
      described, noting the persistence of some elements throughout the late medieval
      and early modern period. Within the theoretical framework and historical setting
      established, the work concludes by showing the complexity and permanent
      interrelationship in the care options, from the point of view of private
      correspondence of the Veciana family at the end of the XVIII century.

PMID- 12001933
TI  - [Fragments of the constant memory of Luis Garcia Ballester. I. The beginnings in
      the nineteen-seventies].

PMID- 12001934
TI  - [At the death of a friend].

PMID- 12001935
TI  - Luis.

PMID- 12001936
TI  - Luis Garcia Ballester and Galen.

PMID- 12001937
TI  - [Contribution of Luis Garcia Ballester to the intellectual history of medieval
      medicine].

PMID- 12001938
TI  - [Luis Garcia Ballester and the medicine of minorities of Spain].

PMID- 12001940
TI  - Bibliography. Current world literature. Infectious diseases.

PMID- 12001939
TI  - [An example of medical practice in al-Andalus: Treatise XIX of the Kitab al
      tarsif of Abu-L-Qasim al-Zahrawi (c. 936-1013)].
AB  - This article reports a study of Treatise XIX from Abu-L-Qasim al-Zahrawi's Kitab
      al-tarsif, according to the Arabic manuscript no. 5772 in the Paris National
      Library. A translation is provided. Folios 89v and 90r, which include chapter 8
      of part II of the treatise, are reproduced from the manuscript.

PMID- 12001941
TI  - Is the modern high potential dairy cow suitable for organic farming conditions?
AB  - It is not acceptable to compromise animal welfare in any system of farming.
      Feeding should be aimed at meeting the nutritional requirements at the various
      stages of production. This paper deals with the detrimental effects that organic,
      extensive or low input farming systems may have on the energy status in early
      lactation of the high potential dairy cow. Bovine ketosis is the most important
      disease resulting from insufficient energy intake in early lactation. It is also
      important to realize that ketosis is a part of the so-called periparturient
      disease complex, which includes milk fever, mastitis, retained placenta,
      endometritis and poor fertility also. All these diseases are interrelated and
      reflect to a large extent the nutritional status of the animal. If organic dairy
      farming is to be successful the breeding programmes have to divert from selection
      for high yields as a main goal, to more emphasis on a flatter lactation curve,
      less production diseases and longevity.

PMID- 12001942
TI  - From the Centers for Disease Control and Prevention. Annual smoking attributable
      mortality, years of potential life lost and economic costs--United States, 1995
      1999.

PMID- 12001943
TI  - From the Centers for Disease Control and Prevention. Suspected cutaneous anthrax
      in a laboratory worker--Texas, 2002.

PMID- 12001945
TI  - Sildenafil and physical exertion in men with coronary artery disease.

PMID- 12001946
TI  - Biophysical considerations concerning gravity receptors and effectors including
      experimental studies on Phycomyces blakesleeanus.
AB  - Part I. Migration and Diffusion of Graviceptors: The physical action of
      gravitational and inertial forces on graviceptors is considered. The motion of
      graviceptors as influenced by physical dimensions, density, electric charge,
      composition of the suspending medium and flow variables is demonstrated. Part II.
      Observations on Geotropism in Phycomyces blakesleeanus: Mutants of Phycomyces
      blakesleeanus exhibit strikingly different rates of geotropic response. It is
      shown that Phycomyces grown in the dark lack normal geotropic responses: pre
      exposure to light is necessary for the synthesis of structures responsible for
      geotropism. A physical model is presented that may account for some of the
      geotropic phenomena observed in Phycomyces.

PMID- 12001947
TI  - Gravity sensing by plants.
AB  - A brief description of the effects of gravity on plants, particularly their
      orientation with reference to its direction, is followed by a presentation of
      evidence for the operation of specific "gravity sensors", statoliths, subcellular
      bodies which move or reorient themselves upon reorientation of a plant organ with
      respect to the direction of the force of gravity. In the singly reacting apical
      cells of rhizoids of Chara, the statoliths locally regulate the growth of the
      cell wall simply by blocking or permitting the access of carriers of cell wall
      material. In multicellular structures (root and stem tips etc.) the statoliths,
      most likely amyloplasts (starch-containing plastids), must act by creating in the
      organ a transversal polarity which can be transmitted to the growing region,
      often several millimetres away. In addition, gravity produces what may be called
      tonic effects, which quantitatively modify the reaction of the organ to the
      gravitational stimulation.

PMID- 12001948
TI  - Effect of free fall on higher plants.
AB  - The influence of exposure to the free fall state on the orientation,
      morphogenesis, physiology, and radiation response of higher plants is briefly
      summarized. It is proposed that the duration of the space-flight experiments has
      been too brief to permit meaningful effects of free fall on general biochemistry,
      growth and development to appear. However, two types of significant effect did
      occur. The first is on differential growth, i.e. tropism and epinasty, resulting
      from the absence of a normal geostimulus. For these phenomena it is suggested
      that ground-based experiments with the clinostat would suffice to mimic the
      effect of the free fall state. The second is an apparent interaction between the
      radiation response and some flight condition, yielding an enhanced microspore
      abortion, a disturbed spindle function, and a stunting of stamen hairs. It is
      suggested that this apparent interaction may be derived from a shift in the
      rhythm of the cell cycle, induced by the free fall.

PMID- 12001949
TI  - Effects of space flight factors on Drosophila.
AB  - Drosophila melanogaster flies of strain D-32 were exposed aboard the Soyuz 10
      spaceship. An insert with a nutritional medium and insects was placed in a small
      on-board thermostat (Biotherm II) providing a constant temperature (24 degrees C
      +/- 1 degree) for Drosophila development. The frequency of dominant lethals was
      determined in the females. Dominant, autosomal and sex-linked recessive lethals
      were estimated in hatching virgin males and females; the time of hatching was
      rigorously fixed. Sex-linked recessive lethals were related to certain stages of
      gametogenesis. The 1-5 oocyte stage showed an increased sensitivity to space
      flight factors as regards the frequency of both dominant and recessive lethals.

PMID- 12001950
TI  - Effects of gravity on ontogeny in animals.
AB  - This brief review leads to the following conclusions: (i) Inversion or clinostat
      rotation of frogs' eggs demonstrated a critical period of enhanced gravity
      sensitivity prior to the first cleavage. These results were corroborated by
      centrifugation studies which localized the period of maximal sensitivity at
      approximately 20 minutes post-fertilization. (ii) Eggs of various invertebrates
      suspended in aqueous solution proved capable of normal development following
      brief ultracentrifugation. (iii) Among fly larvae, grasshopper nymphs, turtles,
      mice, rats and chickens, growth rates were inversely related to G-force and
      maximal chronic acceleration tolerated was inversely related to body size. (iv)
      Body composition data demonstrated the importance of separately evaluating fat
      and the fat-free portion of the body in studies of the effect of acceleration on
      growth in homeotherms. (v) The attempt to evaluate the effect of weightlessness
      on development of frogs' eggs in Biosatellite 2 was inconclusive for technical
      reasons.

PMID- 12001951
TI  - Effects of weightlessness in man.
AB  - The program for the Apollo 16 flight was designed to include both safeguards
      against and investigations of the physiological problems arising from increase in
      the period of manned space flight. Precautions included the provision of a
      controlled diet with high potassium content, carefully controlled work loads and
      work-rest cycles and an emergency cardiology consultation service, and
      investigations were made to enable pre-flight-post-flight comparisons of
      metabolic, cardiovascular and central nervous system data. Results of these
      investigations indicate that adjustment to weightlessness can be satisfactorily
      assisted by appropriate countermeasures including attention to diet.

PMID- 12001952
TI  - Effects of chronic acceleration in animals.
AB  - Chronic acceleration describes the exposure of animals to increased acceleration
      fields of sufficient intensity and duration to induce physiological adaptation.
      By comparing the degree of changes observed in several fields with the
      acceleration intensity, it is possible to derive an estimate of the biological
      effect of gravity. For technical reasons, such studies are limited to artificial
      fields produced by protracted centrifugation. Observations by various
      investigators indicate a fairly general response to chronic acceleration. Over
      the size range presented by these species (0.04-5 kg), there appears to be a
      direct relationship between body mass and the degree of the acceleration-induced
      effect (tolerable field intensity, growth repression, inhibition of fat
      (correction of far) deposition, etc.). However, different response patterns may
      obtain in homeotherms that differ significantly from this body size range.

PMID- 12001953
TI  - Frequency of heavy ions in space and their biologically important
      characteristics.
AB  - A review of the galactic cosmic ray energy spectra of heavy ions with Z< or = 28
      is presented. Fluxes of these ions within critical body organs of astronauts
      travelling outside the magnetosphere will be modified from the free space values
      by fragmentation within the spacecraft and the bodies of the astronauts
      themselves. The effects of such fragmentation are presented in terms of
      variations in the particle flux above a given dE/dx at representative depths.
      Present limitations to the accuracy of such calculations are considered. The
      validity of dE/dx as a relevant physical parameter for characterizing the
      biologically important component of the heavy ion radiation environment is
      discussed.

PMID- 12001954
TI  - Biological effects due to single accelerated heavy particles and the problems of
      nervous system exposure in space.
AB  - The use of accelerated nitrogen and oxygen nuclei with 270 MeV nucleon-1 at the
      Berkeley Bevatron allowed a beginning to be made of systematic studies of the
      effects of heavy particles in multicellular organisms. Initial studies will be
      briefly reviewed. Individual nitrogen particles produced definite light flashes,
      streaks and interrupted streaks when they crossed light-sensitive parts of the
      human retina. The possible hazard from primary heavy galactic cosmic ray
      particles on long-term space flights are discussed, with special attention to the
      nervous system.

PMID- 12001955
TI  - The radiobiological effects of heavy ions on mammalian cells and bacteria.
AB  - The radiobiological effects of heavy ions have been studied in experiments with
      mouse corneal epithelium, liver cells of rats irradiated in vivo, and the
      bacterium Escherichia coli B. From exposure of E. coli B to radiations with
      different LET, the effectiveness of the modifying influence of anoxia and some
      other radioprotectors has been determined.

PMID- 12001956
TI  - Cellular effects of heavy charged particles.
AB  - The human cell is rendered reproductively inactive by the passage of a single
      heavy ion through its nucleus when the heavy ion deposits energy at a rate
      greater than about 3500 MeV cm-1. This is demonstrated by the correlation of
      inactivation probability with nuclear area when cells having nuclei of different
      sizes are compared. This single-hit inactivation is irreversible and
      unmodifiable. The ion path length over which cells will be inactivated in this
      way is calculable from stopping power theory. Laboratory experiments in which
      three-dimensional human cell cultures were irradiated with high-energy nitrogen
      ions (3.9 GeV) at the Princeton Particle Accelerator confirm that cells are
      inactivated with maximum probability over the last 0.5 cm of the ion trajectory.
      This means that groups of adjacent cells in the ion path will be inactivated by a
      single ion with high probability. Organized systems of multiplying cells would be
      expected to amplify this spatially correlated effect of heavy ion irradiation.
      Abnormalities induced in Zea seedlings by heavy ion irradiation of seeds are
      consistent with the inactivation of embryonic cells in groups.

PMID- 12001957
TI  - On the effect of ionizing radiation upon the retina in man and animals.
AB  - The phenomenon of light flashes observed by the American cosmonauts on exposure
      to primary cosmic radiation during translunar flights, and also perceived by
      other observers on exposure of the eye to neutrons from accelerators, is indeed
      one of the latest manifestations of the sensitivity of the retina to very high
      energy radiation. The usual interpretations of this phenomenon are based either
      on the hypothesis of Vavilov-Cherenkov radiation in the ocular media, or on the
      direct stimulation of photoreceptors in the retina itself. The data available are
      submitted to adequate analysis, the experimental materials concerning the
      radiobiology of the retina are generalized, and a conclusion is drawn as to the
      most probable mechanism of light flashes considered as signals damaging the outer
      segments of the rods by particles arising from nuclear reactions in the retina.

PMID- 12001958
TI  - The Biostack experiment on Apollo 16.
AB  - The object of the Biostack experiment is to study the biological effects of high
      ZE particles of cosmic radiation in order to obtain information on the mechanism
      of these particles in biological matter. For this purpose individual local
      evaluation methods have been developed which allow one to identify each
      biologically effective particle and to correlate the individual hitting particle
      with the biological effect produced. The Biostack experimental package contains a
      series of monolayers of selected biological objects (Bacillus subtilis spores,
      Arabidopsis thaliana seeds, Vicia faba radiculae, Artemia salina eggs) with each
      layer sandwiched between several different cosmic ion track detectors (nuclear
      emulsions, cellulose nitrate, polycarbonate). By this arrangement a variety of
      biological effects due to a single penetrating particle can be analysed.
      Influence on cellular and tissue development, nuclear damages, and mutation
      induction are the main investigated effects. These space flight findings will be
      completed by results of balloon flight and accelerator experiments.

PMID- 12001959
TI  - Post-traumatic stress disorder.

PMID- 12001960
TI  - Post-traumatic stress disorder.

PMID- 12001961
TI  - Post-traumatic stress disorder.

PMID- 12001962
TI  - Post-traumatic stress disorder.

PMID- 12001963
TI  - Mortality among patients admitted to hospitals on weekends as compared with
      weekdays.

PMID- 12001964
TI  - Mortality among patients admitted to hospitals on weekends as compared with
      weekdays.

PMID- 12001965
TI  - Dosimetric and biological results from the Bacillus subtilis Biostack experiment
      with the Apollo-Soyuz Test Project.
AB  - The evaluation of the Bacillus subtilis experiment has been completed. The
      biological and the physical results for this part of the Apollo-Soyuz Test
      Project (ASTP) Biostack experiment are given. This comprises dosimetric data for
      the cosmic radiation at that orbit as well as biological findings from two types
      of plastic detectors. Further, the frequency distributions of the physical
      quantities atomic number, energy and energy loss of the heavy ions within the
      sample of spores hit are presented. The biological hazard presented by cosmic HZE
      particles has been much underestimated.

PMID- 12001966
TI  - Closed ecology in space from a bioengineering perspective.

PMID- 12001967
TI  - Technology requirements for nonterrestrial ecosystems.
AB  - Factors associated with planning and implementing research and development for
      nonterrestrial closed-ecology life support systems have been analyzed in terms of
      systems engineering considerations. These factors are discussed in this paper to
      provide a planning overview. It is anticipated that systems of this type probably
      will be required for future manned space activities that would involve many
      participants in a space habitat, particularly at remote locations or for long
      duration missions. Of particular interest are design scenarios that involve
      nonterrestrial ecosystems. Although these approaches offer the promise of being
      able to provide food regeneration by conventional processes, such as
      photosynthesis and essentially terrestrial agricultural methodology, the
      potential impact of nonterrestrial environmental conditions on these processes
      and criteria for ecological stability are not adequately defined. The role of
      these factors in research planning is discussed, and potentially relevant areas
      of research are described.

PMID- 12001968
TI  - Closed regenerative life support systems for space travel: their development
      poses fundamental questions for ecological science.

PMID- 12001969
TI  - The effects of ultraviolet light on the degradation of organic compounds: a
      possible explanation for the absence of organic matter on Mars.
AB  - The analysis of the top layer of the Martian regolith at the two Viking landing
      sites did not reveal any indigenous organic compounds. However the existence of
      such compounds at deeper layers cannot be ruled out. Cosmochemical considerations
      indicate various potential sources for organic matter on Mars, such as comets and
      meteorites. Its disappearance from the top layer could be caused by degradation
      processes on the surface of the planet. Possible destructive agents include
      ultraviolet light, oxygen and metal oxides. In this study we tested the stability
      of a sample of the Murchison meteorite and various organic substances which have
      been detected in carbonaceous chondrites, such as glycine, adenine and
      naphthalene, to the action of ultraviolet light. The compounds were adsorbed on
      powdered quartz and on California desert soil and were irradiated in the presence
      or absence of oxygen. The organic content, before and after irradiation, was
      measured by carbon elementary analysis, UV-absorption, amino acid analysis or
      pyrolysis-gas chromatography-mass spectrometry. In the absence of oxygen, adenine
      and glycine appear to be stable over the given period of irradiation. A definite
      degradation was noticed in the case of naphthalene and the Murchison meteorite.
      In the presence of oxygen in amounts comparable to those on Mars all compounds
      were degraded. The degree of degradation was influenced by the irradiation time,
      temperature and oxygen content.

PMID- 12001970
TI  - Life sciences and space research volume XVII. Proceedings of the Open Meeting of
      the Working Group on Space Biology of the Twenty-first Plenary Meeting of COSPAR,
      Innsbruck, Austria, 29 May-10 June 1978 and Symposium on Gravitational
      Physiology, Innsbruck, Austria, 2 and 3 June 1978.

PMID- 12001971
TI  - Status of certain additional over-the-counter drug category II and III active
      ingredients. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule stating that a
      certain ingredient in over-the-counter (OTC) drug products is not generally
      recognized as safe and effective or is misbranded. FDA is issuing this final rule
      after considering the reports and recommendations of various OTC drug advisory
      review panels and public comments on proposed agency regulations. This final rule
      addresses the ingredient octoxynol 9, considered in the rulemaking for OTC
      vaginal contraceptive drug products. Based on the failure of interested parties
      to submit new data or information to FDA under the proposed regulation, the
      agency has determined that the presence of this active ingredient in an OTC drug
      product would result in that drug product not being generally recognized as safe
      and effective for its intended use or would result in misbranding. This final
      rule is part of FDA's ongoing OTC drug product review.

PMID- 12001972
TI  - Status of certain additional over-the-counter drug category II and III active
      ingredients. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule stating that the
      stimulant laxative ingredients aloe (including aloe extract and aloe flower
      extract) and cascara sagrada (including casanthranol, cascara fluidextract
      aromatic, cascara sagrada bark, cascara sagrada extract, and cascara sagrada
      fluidextract) in over-the- counter (OTC) drug products are not generally
      recognized as safe and effective or are misbranded. This final rule is part of
      FDA's ongoing OTC drug product review.

PMID- 12001973
TI  - Increased vitamin A intake in children aged 2-5 years through targeted home
      gardens in a rural South African community.
AB  - OBJECTIVES: To determine vitamin A intake of children aged 2-5 years in a rural
      South African community one year after the implementation of a home-based food
      production programme targeting beta-carotene-rich fruits and vegetables. DESIGN:
      Dietary intake of children aged 2-5 years was determined during a cross-sectional
      survey before and one year after the implementation of a home-based food
      production programme. SETTING: A low socio-economic rural African community,
      approximately 60 km northwest of the coastal city of Durban in KwaZulu-Natal,
      South Africa. SUBJECTS: Children aged 2-5 years (n = 100); 50 children from
      households with home-gardens producing beta-carotene fruits and vegetables
      (project gardens), and 50 children from households without project gardens.
      RESULTS: As compared with baseline data, there was a significant increase in
      vitamin A intake in children from households with project gardens as well as in
      children from households without project gardens. However, children from
      households with project gardens had a significantly higher vitamin A intake than
      children from households without project gardens. The increased vitamin A intake
      in those children from households without project gardens can be attributed to
      the availability of butternuts in the local shop (as a result of the project),
      and because the mothers negotiated with project garden mothers to obtain these
      fruits and vegetables for their children. CONCLUSION: A home-based food
      production programme targeting beta-carotene-rich fruits and vegetables can lead
      to an increase in vitamin A intake.

PMID- 12001974
TI  - Defining nutritional status of women in developing countries.
AB  - OBJECTIVE: To define a de facto reference body mass index (BMI) for women in
      developing countries and compare its performance with the Quetelet BMI. DESIGN: A
      logarithmic equation for elite wt/ht references was developed using the weight
      (wt) and height (ht) of 10,524 non-pregnant elite mothers. Functional outcomes
      were compared using both BMIs. SETTING: Forty-six national surveys from 36
      developing countries. SUBJECTS: Mothers 15-49 years old. RESULTS: The defacto
      reference standard deviation showed 2.2% of elite women were undernourished and
      6.3% overnourished; lower and upper limits for 'ideal' wt/ht were 73% and 137%,
      respectively. Compared with the age-based and medium frame standards of the First
      and Second National Health and Nutrition Examination Surveys (NHANES I & II), the
      defacto reference defined fewer women as undernourished (5.3% vs. 10.5% and
      14.4%, respectively), but more as overnourished (20.4% vs. 13.7% and 15.9%,
      respectively). In the de facto reference, BMI = wt/ht(1.6). Using the age-based
      and medium-frame-based Quetelet BMI (wt/ht2), 28.5% and 31.7% had a low and 13.0%
      and 14.7% a high BMI, respectively. For the defacto reference, 18.4% of the elite
      mothers had a low BMI and 19.3% a high BMI. Applying the de facto reference to
      all women showed that the distribution of BMI was similar irrespective of the
      reference used. Functional outcomes were similar for both BMIs. CONCLUSIONS: The
      NHANES I & II growth curves define more women as overnourished than the de facto
      curve, but the opposite for defining the undernourished. Functional outcomes were
      similar for both BMIs, suggesting there is no great advantage to using a defacto
      BMI based on national-level data from these 46 national surveys.

PMID- 12001975
TI  - Mortality in British vegetarians.
AB  - OBJECTIVE: To compare the mortality of British vegetarians and non-vegetarians.
      DESIGN: Analysis of original data from two prospective studies each including a
      large proportion of vegetarians--the Oxford Vegetarian Study and the Health Food
      Shoppers Study. Standardised mortality ratios (SMRs) compared with the population
      of England and Wales were calculated from deaths before age 90 for vegetarians
      and non-vegetarians in each study. Death rate ratios (DRRs) for vegetarians
      compared with non-vegetarians within each study were calculated for each of 14
      major causes of death. SETTING: UK. SUBJECTS: Twenty-one thousand men and women
      aged 16-89 years at recruitment, including more than 8,000 vegetarians. RESULTS:
      SMRs for all causes of death were significantly below the reference level of 100
      in both studies: 52 (95% confidence interval (CI) 49-56) based on 1,131 deaths in
      the Oxford Vegetarian Study and 59 (57-61) based on 2,346 deaths in the Health
      Food Shoppers Study. For all causes of death, the DRR for vegetarians compared
      with non-vegetarians was close to one in both studies: 1.01 (95% CI 0.89-1.14) in
      the Oxford Vegetarian Study, 1.03 (0.95-1.13) in the Health Food Shoppers Study.
      CONCLUSIONS: British vegetarians have low mortality compared with the general
      population. Their death rates are similar to those of comparable non-vegetarians,
      suggesting that much of this benefit may be attributed to non-dietary lifestyle
      factors such as a low prevalence of smoking and a generally high socio-economic
      status, or to aspects of the diet other than the avoidance of meat and fish.

PMID- 12001976
TI  - The impact of a nutrition education programme on the anthropometric nutritional
      status of low-income children in South Africa.
AB  - OBJECTIVE: The study determined the impact of a community-based nutrition
      education programme, using trained community nutrition advisors, on the
      anthropometric nutritional status of mixed-race children aged between 2 and 5
      years. DESIGN AND SETTING: The programme was implemented over two years in four
      study areas in the Free State and Northern Cape Provinces. Two control areas were
      included to differentiate between the effect of the education programme and a
      food aid programme that were implemented simultaneously. Weight-for-age, height
      for-age and weight-for-height were summarised using standard deviations from the
      NCHS reference median. For each of the indicators, the difference in the
      percentage of children below minus two standard deviations from the reference
      NCHS median in the initial and follow-up surveys was determined. SUBJECTS:
      Initially 536 children were measured and, after two years of intervention, 815.
      RESULTS: Weight-for-age improved in all areas, but only significantly in boys and
      girls in the urban study area, and in boys in one rural study area. No
      significant improvement in height-for-age occurred in any area. Weight-for-height
      improved significantly in the urban study area. CONCLUSION: The education
      programme in combination with food aid succeeded in improving the weight status
      of children, but was unable to facilitate catch-up growth in stunted children
      after two years of intervention.

PMID- 12001977
TI  - The cognitive contexts of beliefs about the healthiness of meat.
AB  - OBJECTIVE: The overall aim of this study was to examine a variety of belief and
      demographic factors that are associated with the perception that meat is
      intrinsically unhealthy. DESIGN: State-wide survey (written questionnaire) that
      included questions on meat and nutrition beliefs, perceived barriers and benefits
      of vegetarian diets, personal values, number of vegetarian friends and family
      members, and use and trust of health/nutrition/food information sources. SETTING:
      South Australia. SUBJECTS: Six hundred and one randomly selected South
      Australians and 106 non-randomly selected vegetarians and semi-vegetarians.
      RESULTS: For all respondents considered as a group, the most important predictors
      of the belief that meat is intrinsically unhealthy were the perceived benefits of
      vegetarian diets (all positive predictors). These included: (1) the perceived
      links between vegetarianism, peace and increased contentment; (2) animal welfare
      and environmental benefits; and (3) health benefits. There were differences
      between different dietary groups however. For non-vegetarians, social concerns
      about vegetarianism (positive) were most important, followed by health and non
      health benefits (positive) of vegetarianism. Red meat appreciation was the
      strongest (positive) predictor for vegetarians, with health benefits of
      vegetarianism (positive) and education (negative predictor) also important.
      CONCLUSIONS: The implications of the findings for health and other issues are
      discussed. Judgements about the healthiness of meat are likely to be related to
      moral and environmental beliefs and, for non-vegetarians, to social concerns
      about vegetarianism, in addition to health beliefs. These need to be considered
      if any attempts are made to influence meat consumption.

PMID- 12001978
TI  - Nutritional advice to increase soluble fibre intake does not change plasma folate
      or homocysteine in men with angina: a randomised controlled trial.
AB  - OBJECTIVE: To study the effect of advice to increase dietary soluble fibre,
      including fruit and vegetables, on plasma folate and homocysteine in men with
      angina. DESIGN: Data were collected on a subset of subjects from the Diet and
      Angina Randomised Trial (DART II). In a randomised (2 x 2) factorial design,
      subjects received advice on either, neither or both interventions to: (1)
      increase soluble fibre intake to 8.0 g day(-1) (fruit, vegetables and oats); (2)
      increase oily fish intake to 2 portions week(-1). Those who received soluble
      fibre advice were compared with those who did not. Subjects were genotyped for
      C677T variant 5,10-methylenetetrahydrofolate reductase (MTHFR). SETTING/SUBJECTS:
      Seven hundred and fifty-three male angina patients were recruited from general
      practice. RESULTS: Plasma homocysteine concentrations were at the upper end of
      the normal range (median 11.5, 25% 9.4, 75% 14.0 micromol l(-1)). Baseline intake
      of fruit and vegetables was positively correlated with plasma folate (r(s) =
      0.29, P < 0.01). Smokers had lower intakes of fruit and vegetables, lower plasma
      folate and higher homocysteine (all P < 0.01). Homozygotes for variant MTHFR had
      higher homocysteine concentrations at low plasma folate (P < 0.01). Reported
      intakes of fruit and vegetables and estimated dietary folate increased in the
      intervention group (ca. +75 g day(-1), P < 0.01 and ca. +20 g day(-1), P < 0.05,
      respectively). However, neither plasma folate (baseline/follow-up 4.5 vs. 4.4
      microg l(-1), P = 0.40) nor homocysteine (baseline/follow-up 11.7 vs. 11.7
      micromol l(-1), P = 0.31) changed. CONCLUSIONS: Plasma homocysteine, a
      cardiovascular risk factor, is influenced by MTHFR genotype, plasma folate and
      smoking status. Dietary advice successfully led to changes in fruit and vegetable
      intake, but not to changes in plasma folate or homocysteine, possibly because the
      fruits and vegetables that were chosen were not those richest in folate.

PMID- 12001979
TI  - Food and nutrient intakes of a population sample of 3-year-old children in the
      south west of England in 1996.
AB  - OBJECTIVE: To investigate food and nutrient intakes in 3-year-old children.
      SUBJECTS: Eight hundred and sixty-three children resident in South West England
      (69% of those invited at this age), a randomly selected sub-sample of the Avon
      Longitudinal Study of Pregnancy and Childhood (ALSPAC). METHODS: Diet was
      assessed using a 3-day descriptive food record. Food and nutrient intakes were
      compared with intakes at 18 months in the same children, with intakes in the
      British National Diet and Nutrition Survey (NDNS) of pre-school children, and
      with dietary reference values (DRVs). RESULTS: Intakes of energy and most
      nutrients had increased between 18 and 43 months. The macronutrient content of
      the diet had also changed, the percentage of energy from starch rose from 21 to
      23% and from non-milk extrinsic (NME) sugar from 12 to 16%, while the
      polyunsaturated to saturated fat ratio increased from 0.26 to 0.33. When compared
      with the NDNS, intakes of energy and all nutrients were higher with the exception
      of NME sugar. Energy intakes were below the estimated average requirements. Mean
      intakes of iron and vitamin D were below the Reference Nutrient Intake. Fewer
      children were eating beef at 43 months than at 18 months. Total daily meat
      consumption was lower than in the NDNS. The proportion of children consuming any
      vegetables dropped between 18 and 43 months, although fruit eating remained
      constant. CONCLUSIONS: The diets of 3-year-olds in this study were adequate in
      most nutrients. Our results suggest that energy requirements of pre-school
      children in the 1990s are less than the DRV. Nutrient and food intakes changed
      between 18 and 43 months. Children were eating less meat than their counterparts
      in the NDNS.

PMID- 12001980
TI  - Relationships between nutrition screening checklists and the health and well
      being of older Australian women.
AB  - OBJECTIVES: To examine associations between nutrition screening checklists and
      the health of older women. DESIGN: Cross-sectional postal survey including
      measures of health and health service utilisation. as well as the Australian
      Nutrition Screening Initiative (ANSI), adapted from the Nutrition Screening
      Initiative (NSI). SETTING: Australia, 1996. SUBJECTS: In total, 12,939 women aged
      70-75 years randomly selected as part of the Australian Longitudinal Study on
      Women's Health. RESULTS: Responses to individual items in the ANSI checklist, and
      ANSI and NSI scores, were associated with measures of health and health service
      utilisation. Women with high ANSI and NSI scores had poorer physical and mental
      health, higher health care utilisation and were less likely to be in the
      acceptable weight range. The performance of an unweighted score (TSI) was also
      examined and showed similar results. Whereas ANSI classified 30% of the women as
      'high-risk', only 13% and 12% were classified as 'high-risk' by the NSI and TSI,
      respectively. However, for identifying women with body mass index outside the
      acceptable range, sensitivity, specificity and positive predictive values for all
      of these checklists were less than 60%. CONCLUSIONS: Higher scores on both the
      ANSI and NSI are associated with poorer health. The simpler unweighted method of
      scoring the ANSI (TSI) showed better discrimination for the identification of 'at
      risk' women than the weighted ANSI method. The predictive value of individual
      items and the checklist scores need to be examined longitudinally.

PMID- 12001981
TI  - Dietary conjugated linoleic acid (CLA) intake assessment and possible biomarkers
      of CLA intake in young women.
AB  - OBJECTIVE: The habitual intake of the conjugated linoleic acid (CLA) isomer C18:2
      c9t11 (rumenic acid, RA) was assessed and compared with plasma biomarkers.
      DESIGN: The newly developed food-frequency questionnaire (FFQ) comprised 46 food
      items and was validated by means of a 7-day estimated record (7-d ER).
      Additionally, the dietary intake results of the FFQ, 7-d ER, the last day (1-d
      ER) and the last two days (2-d ER) before blood sampling of the 7-d ER were
      compared to the content of C18:2 c9t11 in plasma phospholipids (PL) and
      triglycerides (TG) as possible biomarkers. SETTING: Metabolic unit of a
      university institute. SUBJECTS: Fifty-seven students completed both dietary
      instruments. From all participants fasting blood samples were taken. RESULTS:
      Mean daily intake of rumenic acid was 246 mg day(-1) and 323 mg day(-1) as
      measured by the FFQ and the 7-d-ER, respectively. The degree of correspondence
      between both assessment methods was acceptable; this is indicated by a total
      kappa value of kappa = 0.31 (P < 0.01) and a Pearson correlation coefficient of r
      = 0.46 (P < 0.01). Rumenic acid content in plasma triglycerides was twice as high
      as found in phospholipids. The correlation between the intake results gained with
      the 7-d ER and the plasma PL contents of C18:2 c9t11 was statistically
      significant; this was also true for the C18:2 c9tl 1 values in plasma TG compared
      with the intake results of one or two days before blood sampling. CONCLUSIONS:
      Regarding RA intake, the FFQ data revealed an acceptable degree of correspondence
      with the 7-d ER data but failed to show significant correlations to the potential
      biomarkers. However, with respect to the results of the 7-d ER, the RA content in
      plasma PL and TG are possible biomarkers of short-term and medium-term intake,
      respectively.

PMID- 12001983
TI  - Dietary patterns: report of an international workshop.

PMID- 12001982
TI  - Comparison of neonatal thyroid-stimulating hormone levels and indicators of
      iodine deficiency in school children.
AB  - OBJECTIVES: To compare thyroid-stimulating hormone (TSH) levels in neonatal cord
      blood between study sites in Bangladesh, Guatemala and the United States. Also,
      to compare neonatal TSH results with indicators of iodine deficiency in school
      children. DESIGN: Consecutive births and, in school children, cross-sectional
      surveys. SETTING: Savar, Bangladesh; San Pedro Sacatepequez, Guatemala; and
      Atlanta, United States. SUBJECTS: In each study site, cord blood was spotted on
      to filter paper and TSH levels determined using a sensitive monoclonal assay. In
      the USA, heel stick blood specimens from newborns spotted on to filter paper were
      also obtained as well as exposure to iodine-containing antiseptics during the
      birthing process. Urine specimens were collected from mothers of newborns and
      tested for iodine concentration. School children in the same areas were surveyed
      for thyroid size by palpation and ultrasonography, and urine specimens collected
      for iodine concentration. RESULTS: Between 141 and 243 cord blood specimens were
      collected from each study site. The prevalence of elevated cord blood TSH levels
      (> 5 mUl(-1)) was high in all study sites, from 58% to 84%. All sites would be
      categorised as having 'severe' iodine deficiency based on WHO/UNICEF/ICCIDD
      criteria. Iodine-containing antiseptics were used during 98% of the births in the
      USA but not in Bangladesh or Guatemala. The neonatal TSH classification indicated
      more severe iodine deficiency levels than classifications based on urinary iodine
      and goitre in school children. CONCLUSIONS: In the USA, elevated TSH levels may
      be partially attributed to use of beta-iodine-containing antiseptics prior to
      birth. We recommend the cautious interpretation of TSH results in newborns for
      the assessment of iodine deficiency disorders when iodine-containing antiseptics
      are used during the birthing process.

PMID- 12001984
TI  - TCM practice in China.

PMID- 12001985
TI  - Unable to resist.

PMID- 12001986
TI  - RAS, the magician.

PMID- 12001987
TI  - Conditional mouse models of sporadic cancer.
AB  - First-generation mouse tumour models, which used transgenic mice or conventional
      knockouts, are now being superseded by models that are based on conditional
      knockouts and mice that carry regulatable oncogenes. In these mice, somatic
      mutations can be induced in a tissue-specific and time-controlled fashion, which
      more faithfully mimics sporadic tumour formation. These second-generation models
      provide exciting new opportunities to gain insight into the contribution of known
      and unknown genes in the initiation, progression and treatment of cancer, and
      mimic human cancer better than ever before.

PMID- 12001988
TI  - Dissecting tumour pathophysiology using intravital microscopy.
AB  - For a systemically administered therapeutic agent to reach neoplastic cells, it
      must enter the blood circulation, cross the vessel wall, move through the
      extracellular matrix and avoid getting cleared by the lymphatics. In tumours,
      each of these barriers is abnormal, changes with space and time, and depends on
      host-tumour interactions. Intravital microscopy has provided unprecedented
      molecular, cellular, anatomical and functional insights into these barriers and
      has revealed new approaches to improved detection and treatment.

PMID- 12001989
TI  - Death and anti-death: tumour resistance to apoptosis.
AB  - Every cell in a multicellular organism has the potential to die by apoptosis, but
      tumour cells often have faulty apoptotic pathways. These defects not only
      increase tumour mass, but also render the tumour resistant to therapy. So, what
      are the molecular mechanisms of tumour resistance to apoptosis and how can we use
      this knowledge to resensitize tumour cells to cancer therapy?

PMID- 12001990
TI  - Scatter-factor and semaphorin receptors: cell signalling for invasive growth.
AB  - Malignant disease occurs when neoplastic cells abandon their primary site of
      accretion, cross tissue boundaries and penetrate the vasculature to colonize
      distant sites. This process --metastasis--is the aberrant counterpart of a
      physiological programme for organ regeneration and maintenance. Scatter factors
      and semaphorins, together with their receptors, help to orchestrate this
      programme. What are the differences between physiological and pathological
      activation of these signalling molecules, and can we exploit them therapeutically
      to prevent metastasis?

PMID- 12001991
TI  - NF-kappaB in cancer: from innocent bystander to major culprit.
AB  - Nuclear factor of kappaB (NF-kappaB) is a sequence-specific transcription factor
      that is known to be involved in the inflammatory and innate immune responses.
      Although the importance of NF-KB in immunity is undisputed, recent evidence
      indicates that NF-kappaB and the signalling pathways that are involved in its
      activation are also important for tumour development. NF-kappaB should therefore
      receive as much attention from cancer researchers as it has already from
      immunologists.

PMID- 12001992
TI  - Asbestos and its lethal legacy.
AB  - Asbestos has become the leading cause of occupationally related cancer death, and
      the second most fatal manufactured carcinogen (after tobacco). In the public's
      mind, asbestos has been a hazard since the 1960s and 1970s. However, the
      knowledge that the material was a mortal health hazard dates back at least a
      century, and its carcinogenic properties have been appreciated for more than 50
      years.

PMID- 12001993
TI  - HeLa cells 50 years on: the good, the bad and the ugly.

PMID- 12001994
TI  - Spinning molecular immunology into successful immunotherapy.
AB  - Until recently, immunotherapies have been of limited success, particularly
      against cancer. However, recent insights into the cells, molecules and signalling
      pathways that regulate immune responsiveness are providing new approaches for
      immunotherapy. In this article, I review some of the most promising molecular and
      cellular targets for immunotherapy and discuss approaches that use these targets
      to amplify immune responses and potentially break antigen-specific tolerance.
      These strategies provide a blueprint for the development of successful
      immunotherapy over the next decade.

PMID- 12001995
TI  - New hope for an AIDS vaccine.
AB  - The twenty-first century has begun with considerable success for new AIDS
      vaccines in macaque models. A common feature of these vaccines is their ability
      to induce high-frequency CD8+ T-cell responses that control, rather than prevent,
      infection with HIV. The new vaccines, which include DNA vaccines and live viral
      vectors, are based on technologies that have been developed since the start of
      the AIDS epidemic. The ultimate promise of these vaccines will be realized only
      when efficacy trials in humans are conducted.

PMID- 12001996
TI  - Effector and memory T-cell differentiation: implications for vaccine development.
AB  - Recent work shows that after stimulation with antigen, CD4+ and CD8+ T cells
      embark on a programme of proliferation that is closely linked with the
      acquisition of effector functions and leads ultimately to memory-cell formation.
      Here, we discuss the signals required for commitment to this programme of
      development and the factors that might influence its progression. Models of the
      pathways of effector and memory T-cell differentiation are discussed, and we
      highlight the implications of this new understanding for the optimization of
      vaccine strategies.

PMID- 12001997
TI  - Tracking T cells with tetramers: new tales from new tools.
AB  - To understand the success or failure of immune responses against pathogens or
      tumours requires the direct measurement of specific lymphocytes. Recently, there
      has been an explosion of data in this field through the use of several new tools
      for measuring the number and function of T cells. This has allowed immunologists
      who study human disease and mouse models of infection and cancer to readily track
      specific T cells--in both time and space. Although there are common patterns,
      over time, each host-pathogen relationship seems to develop unique
      characteristics, as reflected in the quality of the T-cell response.

PMID- 12001998
TI  - Cytolytic pathways in haematopoietic stem-cell transplantation.
AB  - The remarkable activity of donor T cells against malignant cells in the context
      of an allogeneic haematopoietic stem-cell transplantation (HSCT) is arguably, at
      present, the most potent clinical immunotherapy for cancer. However, alloreactive
      donor T cells are also important effector cells in the development of graft
      versus-host disease (GVHD), which is a potentially lethal complication for
      recipients of an allogeneic HSCT. Therefore, the separation of the GVHD and graft
      versus-tumour (GVT) activity of donor T cells has become a topic of great
      interest for many investigators. Recent studies have shown that donor T cells
      make differential use of their cytolytic pathways in mediating GVHD and GVT
      effects. Therefore, the selective blockade or enhancement of cytolytic pathways
      provides an intriguing therapeutic opportunity to separate the desired GVT effect
      from the potentially devastating GVHD.

PMID- 12001999
TI  - The quest for an AIDS vaccine: is the CD8+ T-cell approach feasible?
AB  - The rationale for developing anti-HIV vaccines that stimulate cytotoxic T
      lymphocyte responses is given. We argue that such vaccines will work, provided
      that attention is paid to the development of memory T-cell responses that are
      strong and preferably activated. Furthermore, the vaccine should match the
      prevailing virus clade as closely as possible. Vaccines will have to stimulate a
      wide range of responses, but it is not clear how this can be achieved.

PMID- 12002000
TI  - Ethical issues for vaccines and immunization.
AB  - Vaccination is the only type of medical intervention that has eliminated a
      disease successfully. However, both in countries with high immunization rates and
      in countries that are too impoverished to protect their citizens, many dilemmas
      and controversies surround immunization. This article describes some of the
      ethical issues involved, and presents some challenges and concepts for the global
      community.

PMID- 12002001
TI  - Retrospective and prospective validity of aircraft accident risk indicators.
AB  - Data from a national survey of pilots were used to examine the validity of
      measures for the prediction of aviation accidents that had occurred prior to the
      survey (retrospective analysis) and accidents that occurred after the survey
      (prospective analysis). Separate retrospective and prospective analyses were
      conducted, and 45 measures from the survey were found to be associated
      significantly with accident involvement in the retrospective analysis. However,
      only 13 of those 45 measures achieved significance in the prospective analysis.
      Most of the measures found to be significantly related to accident involvement
      concerned aviation exposure; the remaining measures related to pilots' perceived
      and actual level of caution. The study is unique in its use of a cohort design
      for the examination of aircraft accident risk prospectively, and the results
      suggest the need for caution in the interpretation of retrospective analyses in
      this research domain. Actual or potential applications of this research include
      the design of aviation safety programs and the design or interpretation of
      studies that address indicators of aircraft accident risk.

PMID- 12002002
TI  - The role of the air traffic controller in future air traffic management: an
      empirical study of active control versus passive monitoring.
AB  - Proposals for air traffic management such as Free Flight call for a transfer of
      responsibility for separation between aircraft from air traffic controllers
      (ATCos) to pilots. Under many proposals, the role of the ATCo will change from
      one of active control to passive monitoring. The present study directly compared
      these types of control with respect to ATCo mental workload, conflict detection,
      and memory. Eighteen ATCos participated in an air traffic control simulation of
      Free Flight procedures under moderate and high traffic load. Dependent variables
      included accuracy and timeliness in detecting potential conflicts, accepting and
      handing off aircraft, mental workload (as assessed by a secondary task, heart
      rate variability, and subjective ratings), and memory for aircraft location. High
      traffic density and passive control both degraded conflict detection performance.
      Actual or potential applications of this research include the recommendation that
      designs for future air traffic management keep authority for separation of
      aircraft with the controller.

PMID- 12002003
TI  - Evaluating design proposals for complex systems with work domain analysis.
AB  - In this paper we propose a new framework for evaluating designs based on work
      domain analysis, the first phase of cognitive work analysis. We develop a
      rationale for a new approach to evaluation by describing the unique
      characteristics of complex systems and by showing that systems engineering
      techniques only partially accommodate these characteristics. We then present work
      domain analysis as a complementary framework for evaluation. We explain this
      technique by example by showing how the Australian Defence Force used work domain
      analysis to evaluate design proposals for a new system called Airborne Early
      Warning and Control. This case study also demonstrates that work domain analysis
      is a useful and feasible approach that complements standard techniques for
      evaluation and that promotes a central role for human factors professionals early
      in the system design and development process. Actual or potential applications of
      this research include the evaluation of designs for complex systems.

PMID- 12002004
TI  - Attentional filtering in the design of electronic map displays: a comparison of
      color coding, intensity coding, and decluttering techniques.
AB  - In a series of experiments color coding, intensity coding, and decluttering were
      compared in order to assess their potential benefits for accessing information
      from electronic map displays. Participants viewed electronic battlefield maps
      containing 5 classes of information discriminable by color or intensity, or, in
      the decluttering condition, displayed or removed entirely by a key press.
      Participants were asked questions requiring them to focus on objects within a
      class (objects presented at the same color or intensity) or to integrate data
      between objects in different classes (objects presented at different colors and
      intensities). The results suggested that the benefits of color and intensity
      coding appear to be in segregating the visual field rather than calling attention
      to the objects presented at a certain color or intensity. Interactivity proved to
      be a disadvantage; the time cost of information retrieval outweighed the time
      benefits of presenting less information on the display or even allowing map users
      to customize their displays. Potential applications of this research include a
      cost-benefit analysis for the use of 3 attentional filtering techniques and an
      attempt to quantitatively measure map complexity.

PMID- 12002005
TI  - Effects of warning validity and proximity on responses to warnings.
AB  - The effects of a warning's validity and display characteristics on the responses
      to binary warnings were studied in a categorization task that resembled the
      control of a simulated production environment. Students performed a visual signal
      detection task and were aided by a binary warning indicator. Experimental
      conditions differed in the validity of the warning and its proximity to the
      judged stimulus. Participants' performance improved over the course of the
      experiment, and they partly adjusted their responses to the validity of the
      warnings but continued to respond to nonvalid warnings throughout the experiment.
      It was particularly difficult to ignore the nonvalid information when it was
      integrated with the continuous information. There was evidence for nonoptimal use
      of the information from the warning system, whether it was valid or not valid.
      The results indicate a possible distinction between two dimensions of users'
      trust in warning systems: compliance and reliance. Actual or potential
      implications of this research include improved warning design based on analysis
      of system and operator characteristics.

PMID- 12002006
TI  - Supporting decision making and action selection under time pressure and
      uncertainty: the case of in-flight icing.
AB  - Operators in high-risk domains such as aviation often need to make decisions
      under time pressure and uncertainty. One way to support them in this task is
      through the introduction of decision support systems (DSSs). The present study
      examined the effectiveness of two different DSS implementations: status and
      command displays. Twenty-seven pilots (9 pilots each in a baseline, status, and
      command group) flew 20 simulated approaches involving icing encounters. Accuracy
      of the decision aid (a smart icing system), familiarity with the icing condition,
      timing of icing onset, and autopilot usage were varied within subjects. Accurate
      information from either decision aid led to improved handling of the icing
      encounter. However, when inaccurate information was presented, performance
      dropped below that of the baseline condition. The cost of inaccurate information
      was particularly high for command displays and in the case of unfamiliar icing
      conditions. Our findings suggest that unless perfect reliability of a decision
      aid can be assumed, status displays may be preferable to command displays in high
      risk domains (e.g., space flight, medicine, and process control), as the former
      yield more robust performance benefits and appear less vulnerable to automation
      biases.

PMID- 12002007
TI  - Binaural helmet: improving speech recognition in noise with spatialized sound.
AB  - This study assessed the effects of spatialized sound presentation on a listener's
      ability to monitor target (T) messages in the presence of competing (C) messages
      and high-level (110 dB[A]) background noise (BGN). In a simulated military
      environment, 8 participants wore two-channel, active noise reduction (ANR)
      equipped helmets and listened to combinations of T and C messages (89 dB[A] at
      the ear). T messages were presented synchronously with 0, 1, 2, and 3 C messages
      in four listening modes: (a) BGN + diotic, (b) BGN + dichotic, (c) BGN + spatial
      audio, and (d) quiet + spatial audio. Best overall performance occurred in the
      spatialized modes (c and d) and poorest in the diotic mode (a). As expected,
      speech recognition was better in quiet than in BGN when multiple C messages were
      present. Findings indicate that message spatialization in acoustic space improves
      auditory performance during times of heavy message competition, even in high
      level noise. The proposed technology has numerous applications, such as
      multichannel communications in tactical operations centers, monitoring of complex
      security systems, and air traffic control.

PMID- 12002008
TI  - Behavioral influences of proximal alarms.
AB  - Confidence in and responses to an unreliable test alarm were studied in the
      presence of nearby unspecified alarms. The test alarm's reliability rate was
      represented as averaging "true" only 50% or 60% of the time. Confidence or
      response rates ranged proportionately from 23% to 97% with the number of active
      alarms within 5, 6, 7, or 9 annunciator arrays. Adjacent alarms resulted in
      confidence estimates that were higher (by about 10%) than those with the same
      number of active alarms spaced up to 3 positions away. Simultaneously activated
      alarms resulted in a more than 20% increase in "true" responses compared with the
      same number of alarms offset in time by up to 32 s, regardless of which came
      first. Active alarms "known" to be functionally related to, or independent of,
      the test alarm substantially raised or lowered responding but did not completely
      overcome prior effects. These findings indicate that presumptions that operators'
      responses are not influenced by nearby alarms, regardless of their function, may
      be unwarranted. Applications of this research include suggestions to improve
      responding and training recommendations.

PMID- 12002009
TI  - Context-dependent memory under stressful conditions: the case of skydiving.
AB  - Two experiments examined the effect of differing levels of emotional arousal on
      learning and memory for words in matching and mismatching contexts. In Experiment
      1, experienced skydivers learned words either in the air or on the ground and
      recalled them in the same context or in the other context. Experiment 2
      replicated the stimuli and design of the first experiment except that
      participants were shown a skydiving video in lieu of skydiving. Recall was poor
      in air-learning conditions with actual skydiving, but when lists were learned on
      land, recall was higher in the matching context than in the mismatching context.
      In the skydiving video experiment, recall was higher in matching learn-recall
      contexts regardless of the situation in which learning occurred. We propose that
      under extremely emotionally arousing circumstances, environmental and/or mood
      cues are unlikely to become encoded or linked to newly acquired information and
      thus cannot serve as cues to retrieval. Results can be applied to understanding
      variations in context-dependent memory in occupations (e.g., police, military
      special operations, and Special Weapons and Tactics teams) in which the worker
      experiences considerable emotional stress while learning or recalling new
      information.

PMID- 12002010
TI  - The twilight envelope: a user-centered approach to describing roadway
      illumination at night.
AB  - Visual recognition functions, such as acuity and contrast sensitivity,
      deteriorate rapidly over the declining luminances found during civil twilight.
      Thus civil twilight, a critical part of the transition between daylight and
      darkness, represents lighting conditions that may be useful to describe
      artificial illumination. Automotive headlamps project a three-dimensional beam
      that ranges from illumination levels comparable to daylight at the vehicle to the
      dark limit of civil twilight (3.3 1x) at some distance ahead. This twilight
      envelope is characterized as a distance beyond which foveal visual functions are
      severely impaired, and thus it provides a general, functional description of the
      useful extent of the headlamp beam. This user-centered approach to describing
      illumination is useful for characterizing visibility when driving at night or in
      other artificially lit environments. This paper discusses the twilight envelope
      approach and its application to intervehicle variations in headlamp systems.
      Actual or potential applications of this research include user-centered
      description of artificial illumination and driver/pedestrian safety education.

PMID- 12002011
TI  - Speech-based interaction with in-vehicle computers: the effect of speech-based e
      mail on drivers' attention to the roadway.
AB  - As computer applications for cars emerge, a speech-based interface offers an
      appealing alternative to the visually demanding direct manipulation interface.
      However, speech-based systems may pose cognitive demands that could undermine
      driving safety. This study used a car-following task to evaluate how a speech
      based e-mail system affects drivers' response to the periodic braking of a lead
      vehicle. The study included 24 drivers between the ages of 18 and 24 years. A
      baseline condition with no e-mail system was compared with a simple and a complex
      e-mail system in both simple and complex driving environments. The results show a
      30% (310 ms) increase in reaction time when the speech-based system is used.
      Subjective workload ratings and probe questions also indicate that speech-based
      interaction introduces a significant cognitive load, which was highest for the
      complex e-mail system. These data show that a speech-based interface is not a
      panacea that eliminates the potential distraction of in-vehicle computers. Actual
      or potential applications of this research include design of in-vehicle
      information systems and evaluation of their contributions to driver distraction.

PMID- 12002012
TI  - Team training in the skies: does crew resource management (CRM) training work?
AB  - The aviation community has invested great amounts of money and effort into crew
      resource management (CRM) training. Using D. L. Kirkpatrick's (1976) framework
      for evaluating training, we reviewed 58 published accounts of CRM training to
      determine its effectiveness within aviation. Results indicated that CRM training
      generally produced positive reactions, enhanced learning, and promoted desired
      behavioral changes. However, we cannot ascertain whether CRM has an effect on an
      organization's bottom line (i.e., safety). We discuss the state of the literature
      with regard to evaluation of CRM training programs and, as a result, call for the
      need to conduct systematic, multilevel evaluation efforts that will show the true
      effectiveness of CRM training. As many evaluations do not collect data across
      levels (as suggested by D. L. Kirkpatrick, 1976, and by G. M. Alliger, S. I.
      Tannenbaum, W. Bennett, Jr., & H. Traver, 1997), the impact of CRM cannot be
      truly determined; thus more and better evaluations are needed and should be
      demanded.

PMID- 12002047
TI  - Tobacco use in developing countries.

PMID- 12002048
TI  - Tobacco smoking in Black and White South Africans.
AB  - OBJECTIVES: To provide data on black and white South Africans' tobacco use
      status, belief in the benefits to health of not smoking, risk awareness in terms
      of knowledge of the links between smoking and disease, health status, subjective
      health status and well-being. DESIGN: Randomised study. SETTING: Two urban
      communities in the Northern Province of South Africa. PARTICIPANTS: Two hundred
      and fifty blacks and 250 whites. The black participants were 100 (40%) men and
      150 (60%) women in the age range of 18 to 80 years (mean = 38.9 years, SD=4.7),
      and the white participants were 111 (44.4%) men and 139 (55.6%) women in the age
      range of 19 to 91 years (mean = 41.8 years, SD=3.5). MAIN OUTCOME MEASURES: A
      measure of smoking, health benefits, risk awareness, health status, subjective
      health and subjective well-being. RESULTS: The average prevalence of current
      smoking was 11.2% in Blacks, 23.6% in whites, 31.8% in men and 6.9% in women.
      Age, being male, being white, and being married or living with a partner were
      significantly positively associated with smoking status and smoking frequency.
      Risk awareness of the negative effects of smoking and the belief in the
      importance of not smoking were both significantly negatively associated with both
      smoking status and smoking frequency. CONCLUSION: The prevalence of smoking
      tobacco, especially among males and Whites as well as the low risk awareness of
      smoking is a cause of concern. Stronger beliefs in the importance of not smoking,
      being female and lower age were identified as independent predictors among non
      smokers than smokers.

PMID- 12002049
TI  - Tobacco consumption among primary school teachers in Nairobi.
AB  - OBJECTIVE: To determine the extent, pattern and the attendant risk factors of
      cigarette smoking and tobacco consumption among primary school teachers in
      Nairobi. DESIGN: A descriptive cross-sectional study. SETTING: The study was
      carried out among randomly selected Nairobi City Council primary schools in 1996.
      PARTICIPANTS: All the teachers in the selected primary schools were included in
      the study. RESULTS: Out of 910 teachers contacted, 813 responded (a response rate
      of 89.3%). A total of 800 teachers completed the questionnaire correctly and are
      the subject of the present analysis. Fifty per cent of male and three per cent of
      female teachers were cigarette smokers at the time of the study. The median age
      for starting to smoke was between 15 and 24 years. At this age, the teachers were
      secondary school and tertiary college students. It was observed that the age of
      smoking initiation seems to determine the individual's smoking status later in
      life. CONCLUSION: Since 57% of smokers started smoking during their secondary
      school days, secondary school students seem to be at a higher risk of initiating
      smoking. It is therefore important to target them for smoking control initiatives
      before they start the habit. A number of smokers were willing to quit smoking but
      did not know how to go about it. External assistance is therefore required for
      them to achieve their wish. It is also important to emphasise the need by the
      relevant authorities to initiate programmes for anti-smoking education in
      secondary schools and colleges in the country.

PMID- 12002050
TI  - Characterisation of Vibrio parahaemolyticus isolated from fish in Kenya.
AB  - BACKGROUND: Acute gastroenteritis associated with fish has been reported since
      1951 but is gaining importance with increase in fish consumption in Kenya. The
      causative agent is Vibrio parahaemolyticus. The importance of this organism is
      increasing due to the rise in the incidence of outbreaks of food poisoning
      related to it. OBJECTIVE: To isolate and characterise local strains of Vibrio
      parahaemolyticus from sea and fresh-water fish. DESIGN: A prospective study.
      SETTING: Three lakes, a river, a dam and the Kenyan coastline. SUBJECTS: Water
      and fish samples collected from the study sites. MAIN OUTCOME MEASURES: Isolation
      of Vibrio parahaemolyticus on glucose-salt-teepol broth (GTSB), and
      triphenyltetrazolium chloride soya tryptone (TSAT) and several biochemical media,
      testing the pathogenicity for the isolates by Kanagawa phenomenon and testing the
      plasmids profiles, coagglutination sensitivity to antimicrobial substance using
      standard methods. RESULTS: Twenty nine isolates (4%) were obtained from a total
      of 666 samples screened, twenty seven of which were isolated from 62 coastal
      samples. They were Kanagawa negative although their plasmid profiles and
      sensitivity to antimicrobials varied. CONCLUSION: There is need to recognise V.
      parahaemolyticus as a potential problem due to the increase in consumption of
      fish as an alternative source of protein.

PMID- 12002051
TI  - Impact of lactation management education on health professionals.
AB  - BACKGROUND: In 1992, Kenyatta National Hospital Lactation Management Education
      Centre (KNH LME) was establised in collaboration with the University of Nairobi
      (UoN) and the Ministry of Health (MoH). The aim of the programme was to train
      multidisciplinary teams of health professionals in lactation management
      education. OBJECTIVE: To determine the performance of doctors, nurses and
      nutritionists on lactation management education, before and after exposure to the
      programme. DESIGN: A descriptive analysis of the pre and post test performance of
      doctors, nurses and nutritionists on lactation management education. SUBJECTS:
      Two hundred and twenty nine health professionals, comprising one hundred and
      thirty eight nurses, fifty six nutritionists, and thirty five doctors. RESULTS:
      The performance of all participants improved significantly (p = <.000) between
      the pre and post test scores from a mean score of 54.0% in pre test, to a mean
      score of 72.0% in the post test. CONCLUSION: Adequate lactation management
      education content should be included in all preservice medical curricula for all
      health professionals. In addition, an update of emerging issues in lactation
      management education must be sustained, in all health institutions as part of
      continuing education for inservice health professionals.

PMID- 12002052
TI  - Malaria in children in Ilorin, Nigeria.
AB  - OBJECTIVES: To determine the prevalence of paediatric malaria admissions in an
      area of stable malaria transmission and to ascertain the relative contributions
      of different forms of severe malaria to morbidity and mortality. DESIGN: A
      descriptive restrospective study. SETTING: Olanrewaju hospital, a general
      practice health facility in a malaria holoendemic city in Nigeria. SUBJECTS AND
      METHODS: Case files of paediatric (age < 15years) admissions between 1/1/98 and
      31/12/98with a diagnosis of acute malaria were retrieved and relevant information
      including demographic data, clinical signs, laboratory records, treatments
      received and diagnosis on discharge were extracted. Grouped age-associated
      prevalence rates were calculated; characteristics of different groups were
      compared using standard statistical methods. RESULTS: Children with Falciparum
      malaria accounted for 95 (18%) of the 526 medical admissions. The proportion of
      children admitted with severe malaria was significantly higher among the under
      fives compared to those over five years (p < 0.001; RR = 5.36, 95% CI of 2.58 to
      11.2). Thirty two (33.7%) children had severe malaria. Fifteen (15.8%) had
      convulsions without coma, 13 (13.68%) had malaria-associated anaemia and four
      (4.2%) were diagnosed as having had cerebral malaria. Seizures were significantly
      more frequent in the under-fives (p=0.001, RR=6.0; 95% CI of 1.8 to 19.6). There
      was a significant negative correlation between age and severe anaemia/blood
      transfusions (p = 0.002). Cerebral malaria carried the greatest risk of fatality
      (CFR=25%; RR=7, 95% CI of 1.5 to 91). CONCLUSION: High prevalence of paediatric
      malaria admissions in this study underscores the morbidity burden in Nigerian
      children, especially in under-fives in whom the severe forms are more common. A
      high incidence of anaemia requiring blood transfusions further increases the risk
      of paediatric HIV infection in Nigeria where organised control programmes are
      rudimentary.

PMID- 12002053
TI  - Factors associated with measles complications in Gweru, Zimbabwe.
AB  - OBJECTIVE: To investigate factors associated with complications or death among
      measles cases. DESIGN: A cross-sectional study. SETTING: Health facilities in the
      city of Gweru, Zimbabwe. SUBJECTS: Six hundred and thirty seven measles cases
      randomly selected from measles surveillance data. MAIN OUTCOME MEASURES: (a)
      Associations of respiratory complications and diarrhoea with death among
      complicated cases; (b) associations of age at infection, gender of cases and
      vaccination status of cases with occurrence of either respiratory complications
      or diarrhoea or death among measles cases. RESULTS: Among cases with respiratory
      complications, twenty two (29%) had died, while five (5%) had died among those
      with diarrhoea (OR=7.06,95% CI=2.55-22.35, p<0.001). On rates of respiratory
      complications among cases, age groups 24-59 and 60+ months were protective by 57%
      (95% CI=11-79%) and 76% (95% CI=52-88%) respectively compared to the age group
      <24 months, and vaccination was protective by 42% (95% CI=2-65%) compared to
      those unvaccinated. Concerning rates of diarrhoea among cases, the age group 60+
      months was protective by 80% (95% CI=62-89%) compared to age group <60 months,
      while vaccination was protective by 64% (95% CI=42-77%) compared to those
      unvaccinated. With respect to rates of mortality among cases, age was protective
      by six per cent (95% CI=3-9 %) for every year older. CONCLUSION: It was concluded
      that: (a) the risk of death was higher in cases with respiratory complications
      than diarrhoea; (b) the risk of complications and death was inversely related to
      age at infection and older age groups were protective against occurrence of
      complications or death; (c) the risk of complications was higher in unvaccinated
      cases and vaccination was protective against occurrence of complications.

PMID- 12002054
TI  - Warfarin-related bleeding following open heart surgery in Nairobi.
AB  - OBJECTIVES: To review anticoagulant-related bleeding in heart valve patients on
      warfarin at the Kenyatta National Hospital and to determine the variables
      associated with anticoagulant-related bleeding. DESIGN: A combined retrospective
      and prospective review of patients operated at the Kenyatta National Hospital.
      Retrospective period from June 1973 to 31st July 1997, while prospective period
      from August 1st 1997 to June 1st 2000. SETTING: Surgical Outpatient Department,
      Kenyatta National Hospital, Nairobi. MAIN OUTCOME MEASURES: Linearised occurrence
      rate of anticoagulant-related bleeding and the one- five- and ten- year bleed
      free rates. Independent risk factors associated with anticoagulant-related
      bleeding determined using Cox's proportional hazards. RESULTS: Thirty one
      bleeding episodes were recorded in 150 patients followed up for a total of 745
      patient-years. The risk of occurrence of the first bleed was 16.0%; while the
      risk of a subsequent bleed increased thereafter with a 16.7%, 50% and 50% risk
      after the first, second and third bleeds respectively. The linearised rate for
      minor anticoagulant-related bleed was 4.16% per patient per year however, half
      the bleeds occurred within the first year of valve implantation or previous
      bleeding episode. The one-, five- and ten-year bleed free rates for all valves
      combined were 93%, 85% and 78% respectively. There was no statistically signicant
      difference between the curves comparing the bleed free rates for the first and
      second bleeding episodes (p=0.098). The number of valves implanted, the site of
      implant and the time to the occurrence of bleeding were independent risk factors
      associated with the occurrence of bleeding (p<.05). CONCLUSION: The occurrence of
      anticoagulant-related bleeding is relatively common being slightly above the
      internationally reported range. Most episodes of bleeding will occur within one
      year of hospital discharge or the previous bleeding episode. The risk of another
      bleeding episode occurring increases with each episode with up to a 50% risk of
      re-bleed after the second bleeding episode. In this study, the number of valves
      implanted, their position and the time of occurrence of the bleed were risk
      factors to the occurrence of bleeding.

PMID- 12002055
TI  - HIV infection in elderly medical patients.
AB  - OBJECTIVE: To determine the prevalence and presentation of HIV-infection among
      medical admissions aged 55 years and above. DESIGN: Prospective cross-sectional
      study. SETTING: Dar es Salaam, Tanzania. SUBJECTS: Consecutive patients aged 55
      years and above hospitalised in the medical wards of the Muhimbili Medical Centre
      in Dar es Salaam from February to May 1998. RESULTS: The overall HIV-1
      seroprevalence was 15.0% (38/253); and by sex it was 18.5 % (28/ 151) among males
      compared to 9.8% (10/102) amongfemales (p=0.06). The HIV-1 prevalence among those
      aged 55 to 59 years was 29.7%. There was no association between HIV- 1 serostatus
      and whether one lived in a rural or urban area, marital status, level of
      education nor socio-economic status. The main presenting features in patients who
      were found to be HIV-1 seropositive were wasting 44.7%, fever 39.5%, pallor 34.2%
      and weight loss 31.6%. Only six (15.8%) of the 38 patients were initially
      suspected to have been HIV-infected before laboratory results were obtained.
      CONCLUSIONS: HIV-infection is a notable problem in the population of elderly
      medical admissions in Dar es Salaam. The possibility of HIV-infection should be
      considered among elderly patients with clinical features of immunodeficiency.
      HIV/AIDS prevention programmes directed towards the elderly should be
      established.

PMID- 12002056
TI  - Diagnosis and management of brain tumours at Jos University Teaching Hospital,
      Nigeria.
AB  - OBJECTIVE: To report on the incidence of brain tumours in Jos Plateau of Nigeria
      and to highlight areas of interest regarding diagnosis, management and outcome.
      DESIGN: A retrospective study. SETTING: Jos University Teaching Hospital (JUTH),
      Jos, Nigeria. SUBJECTS: Thirty patients with brain tumours. INTERVENTIONS:
      Specific management of primary lesions was carried out in cases of metastatic
      brain tumours. Steroids were administered in one case of cerebellar
      oligodendroma. Craniotomy and excision was achieved in two cases of meningioma
      and two of sarcoma. Palliative excision was employed in another two cases of
      meningioma. Two cases each of pituitary adenomas were managed by craniotomy and
      excision and trans-nasal transsphenoidal excision. RESULTS: Brain tumours ranked
      third in frequency relative to other tumours. The relative frequency of different
      histological types in percentages were: metastatic (30%), anterior pituitary
      (21%), meningeal (18%), neuroepithelial (15%) and nerve-sheath (6%). The mean age
      of presentation was 33 years. The three commonest clinical features in
      percentages included headaches (43%), cranial masses (39%) and visual defects
      (26%). Eighty three per cent of the total number of patients died within three
      weeks to one year irrespective of management modality employed. Two patients who
      had transnasal excision of pituitary tumours abroad are, however, well and alive
      at one and two years post-operation respectively. CONCLUSION: In this study,
      roentgenograms of the skull had a diagnostic value of 76% for tumours of
      meningeal origin and pituitary adenomas. CT scan is the mainstay for diagnosis of
      brain tumours. The outcome was poor with a mortality of 83%.

PMID- 12002057
TI  - Dental caries and periodontal conditions among primary school children in
      Morogoro municipality, Tanzania.
AB  - OBJECTIVE: To describe the occurrence of dental caries and periodontal conditions
      among standards three and four primary school children in Morogoro municipality
      and compare the obtained oral health indicators with the goals stipulated in the
      National Plan for Oral Health by the year 2002. DESIGN: Cross sectional study of
      the oral health status among eight to 15-year old primary school children.
      SETTING: Primary schools in Morogoro municipality, Tanzania. SUBJECTS AND
      METHODS: A total of 1,297 standards three and four children in five primary
      schools randomly selected from a list of 36 primary schools of Morogoro
      municipality were examined for oral health status. Dental caries and periodontal
      status were recorded using the criteria described in the WHO manual for Oral
      health Surveys, Basic Methods (1997). Oral cleanliness was assessed using plaque
      index. MAIN OUTCOME MEASURES: Dental caries prevalence, experience and its
      distribution by tooth type and jaw and prevalence and severity of periodontal
      conditions and oral cleanliness. RESULTS: Seventy six percent of the children
      were caries free, and the mean DM-T was 0.41. No fillings were encountered.
      Seventy six per cent of carious lesions were in pits and fissures of lower
      molars. Only 21% of the caries lesions were in the pits and fissures of upper
      molars. Seventy five per cent of the children had all sextants with no gingivitis
      or calculus. Mean sextants with gingivitis, calculus and visible plaque were
      0.25, 0.69 and 2.44 respectively. CONCLUSIONS: Standard four and standard four
      children in Morogoro municipality primary schools had very low levels of dental
      caries, good oral hygiene and a very low prevalence of gingivitis. No restorative
      treatment had been provided to these pupils. It is recommended that Morogoro
      municipality should start a dental caries treatment programme in primary schools
      in order to attain the national goal of 10% of the "F" component of DMF-T by the
      year 2002.

PMID- 12002058
TI  - Symptoms in health personnel exposed to disinfectants.
AB  - BACKGROUND: While the biocidal efficacy of disinfectants available for use in
      health facilities has been widely investigated, little attention has been paid to
      their potential side effects to users. OBJECTIVE: To describe the occurrence of
      symptoms attributable to occupational exposure to disinfectants with emphasis on
      gluteraldehyde. DESIGN: Exploratory cross-sectional study. SETTING: Kenyan health
      facilities. SUBJECTS: One hundred and fifteen members of various health cadres.
      RESULTS: All the respondents reported using disinfectants. Glutaraldehyde-based
      preparations, either alone or alongside other agents (excluding hypochlorite),
      were used by 52.2% of the respondents. Hypochlorite-based preparations, either
      alone or alongside other agents, were used by 18.3%, while cetrimide preparations
      and ethanol alongside other agents were used by 13% of the respondents. More than
      sixty two per cent of the respondents had suffered one or more symptoms during
      the use of these disinfectants. Among the users of glutaraldehyde preparations,
      the most common symptoms reported were sneezing (38.3%), headache (31.7%),
      watering of eyes (25%), skin rash (10%) and chronic cough (8.3%). Among users of
      hypochlorite and cetrimide preparations, the most commonly reported symptoms were
      sneezing, headaches and watering of eyes. CONCLUSIONS: Our findings suggest
      possible occupation-related adverse reactions that may be attributed to the use
      of disinfectants. Awareness of these potential hazards needs to be increased
      among users and efforts made to introduce techniques to minimise exposure to
      liquid and vapourised disinfectants. Further studies involving larger sample
      sizes, are necessary to unequivocally apportion the various symptoms to specific
      disinfecting agents.

PMID- 12002059
TI  - Epidemiology of injury patients at Bugando Medical Centre, Tanzania.
AB  - OBJECTIVE: To describe the epidemiologic characteristics of injury cases at
      Bugando Medical Centre. SETTING: Bugando Medical Centre, Mwanza, Tanzania. DATA
      SOURCES: Records, registries and case notes in the surgical wards and clinic,
      casualty, medical record department, radiology and theatre from January 1995 to
      December 1997. STUDY SAMPLE: Cases attended to at Bugando and diagnosed to have
      had an injury during the stated period. Only those whose records were complete
      and available were recruited in the study. DATA EXTRACTION: A special data sheet
      was used to collect the required information from the registries in surgical
      wards clinic, casualty, theatre, radiology and medical records. Data analysis was
      Dbase IV and SPSS (version 9.0). RESULTS: There were 3,590 cases of injury
      recorded at the centre of whom 3340 (93%) whose data were complete were available
      for analysis. Of the cases, 2,443 (73.1%) were males and 897 (26.9%) females
      while 252 (7.7%) were children under five years. The most affected age group were
      the 20-59 year category comprising of mostly males. The leading causes of
      injuries were falls, assault (28.7%) and motor traffic accidents (17.9%).
      Mortality was (2.2%) for all causes, and permanent disability was two per cent.
      The mean length of stay in hospital was 21 days (range: 1-321 days). CONCLUSION:
      A more comprehensive study isrecommended to determine risk factors and magnitude
      of the problem.

PMID- 12002060
TI  - Tumoral calcinosis: case report.
AB  - Tumoral calcinosis (TC) is a rare disease of obscure aetiology. In its classic
      form, it is characterised by solitary or multiple large foci of mineralisation in
      the soft tissue adjacent to the bone around large joints in the absence of
      disorders of calcium metabolism and visceral calcification. A case is presented
      of TC in a 75-year old Kenyan woman.

PMID- 12002061
TI  - Technical efficiency of public clinics in Kwazulu-Natal Province of South Africa.
AB  - BACKGROUND: In sub-Saharan Africa (SSA) much of the attention of policy makers,
      health care managers, health systems researchers and donors is focussed almost
      solely on mobilising additional resources and not on efficiency in their use.
      OBJECTIVE(S): To investigate the technical inefficiencies among 155 primary
      health care clinics in Kwazulu-Natal Province of South Africa; and to draw policy
      implications. DESIGN: Cross-sectional provincial health clinic survey. SELLING:
      Kwazulu-Natal Provincial Department of Health Clinics survey, 1996. SUBJECTS: The
      analysis is based on 155 public clinics. INTERVENTIONS: Non-intervention Data
      Envelopment Analysis (DEA) study. MAIN OUTCOME MEASURES: Technical and scale
      efficiency scores. RESULTS: Forty seven (30%) were found to be technically
      efficient. Among the 108 (70%) technically inefficient facilities, 16% had an
      efficiency score of 50% or less. The presence of inefficiencies indicates that a
      clinic has excess inputs or insufficient outputs compared to those clinics on the
      efficiency frontier. To achieve technical efficiency, Kwazulu-Natal clinics
      would, in total have to decrease inputs by 417 nurses and 457 general staff.
      Alternatively, outputs would have to be increased by 115,534 antenatal visits,
      1,010 births (deliveries), 179,075 child care visits, 5,702 dental visits,
      121,658 family planning visits, 36,032 psychiatric visits, 56,068 sexually
      transmitted disease visits and 34,270 tuberculosis visits. CONCLUSION: There is
      need for more detailed studies in a number of the relativdy efficient clinics to
      determine why they are efficient with a view of documenting attributes of 'best
      practise' that other clinics can emulate. The potential benefit of replicating
      this kind of study in other provinces, and indeed, other SSA countries cannot be
      overemphasised.

PMID- 12002062
TI  - How to develop an operational plan for health.
AB  - BACKGROUND: About 88%, 8%, 36% and 28% of the ministries of health in African
      countries do not have long-term health plans (LTHPs), health policies (HPs),
      strategic plans (SPs), and operational plans (OPs), respectively. Eight per cent,
      38% and 54% of the countries with OPs rated their formulation as 'excellent',
      'satisfactory' and 'needs improvement', respectively. OBJECTIVE(S): To provide a
      rationale for an OP; to describe its contents; and to explain the process of
      developing it. DESIGN: Descriptive study. SETTING: Operational plans in the WHO
      African Region. INTERVENTIONS: Non-intervention descriptive study. MAIN OUTCOME
      MEASURES: Operational plan (OP) for health. RESULTS: An OP framework and process
      that could be adapted by countries is proposed. CONCLUSION: An adequately
      formulated OP will contain objectives, targets, expected results, activities,
      required resources, and a monitoring and evaluation plan (consisting of
      responsibilities, monitoring indicators, evaluation indicators, data sources -
      for verifying indicators, and periodicity). In the next two decades, we envision
      that all the UN agencies and other health partners working in Africa will
      cooperate with individual countries to develop (or strengthen) LTHPs, HPs, SPs,
      and OPs of the Ministries of Health (national, provincial and district level).

PMID- 12002063
TI  - Evaluation of health-related programmes in Africa: a vision for 2020.
AB  - BACKGROUND: Whereas systematic evaluation practice is over five decades old in
      economically developed continents (DCs), that culture has not yet taken root in
      Africa. OBJECTIVE(S): To provide an overview of the current situation of health
      related evaluation in the African Region; to envision an appropriate evaluation
      framework for the next two decades; and to provide overviews of what formative
      (FE) and summative (SE) evaluations are and how they could be conducted. DESIGN:
      Descriptive study. SETTING: Health policies and plans evaluation in the WHO
      African Region. SUBJECTS OR PARTICIPANTS: WHO Country Representatives for 25
      African Countries. INTERVENTIONS: Non-intervention descriptive study. MAIN
      OUTCOME MEASURES: Availability and quality of long-term health plan (LTHP),
      health policy (HP), strategic plan (SP), operational plan (OP), and an evaluation
      culture. RESULTS: The study found that: 88%, 8%, 36%, 28% and 48% of the
      countries in the Region do not have LTHP, HP, SP, OP and evaluation culture. A
      conceptual evaluation framework, tools for formative and summative evaluations
      are proposed. CONCLUSION: It is envisioned that all partners for health
      development in Africa will cooperate with individual countries to develop (or
      strengthen) LTHPs, HPs, SPs, and Ministries of Health OPs (national, provincial
      and district level); and to make complementary investments in building technical
      and administrative capacity for evaluating implementation of District Operational
      Plans (DOPs).

PMID- 12002064
TI  - A case for day-care surgery.

PMID- 12002065
TI  - Practice and acceptance of day-care surgery in a semi-urban Nigerian hospital.
AB  - OBJECTIVE: To determine the acceptability and practicability of day-care surgery
      in a semi-urban area of Nigeria. DESIGN: A twelve- month prospective study.
      SETTING: Wesley Guild Hospital, Ilesa, Nigeria. PATIENTS: Sixty seven consecutive
      patients with ASA I-II status and aged three months to 97 years were studied.
      INTERVENTION: Patients were operated as day-cases using general or local
      anaesthesia. MAIN OUTCOME MEASURES: Practicability, post-operative problems and
      acceptability. RESULTS: The mean age of patients studied was 27.26 years (SD
      23.89), with males accounting for 61% of the 67 cases. Fifty eight per cent and
      42% had general and local anaesthesia respectively. While all patients had post
      operative support from family members, less than seven per cent had access to
      telephone or family doctor services. About 80% of the patients lived within 10 km
      from the hospital. Intermediate operations accounted for 60% of the cases, while
      minor ones accounted for 40%. The mean operating time was 30 minutes.
      Postoperative pain was the only significant problem encountered. This, however,
      decreased in the patients with time. Complication rate was 10.5%. CONCLUSION: A
      significant number of patients accepted and approved of the day stay surgery.
      Medical and surgical practitioners in semi-urban regions are encouraged and
      charged to accept the practice of short stay surgery.

PMID- 12002066
TI  - Attitudes and beliefs of relatives of patients with sickle cell disease.
AB  - OBJECTIVES: To assess the attitudes and beliefs of relatives of eighty one SCD
      sufferers on aspects of the disease, the relationship of their responses with
      global rating of burden, and compare with the responses of relatives of cancer
      patients from a similar previous study. DESIGN: Cross-sectional survey. SETTING:
      Haematology outpatient clinic. MEASUREMENTS: Burden questionnaire and Goldberg's
      GHQ-12. RESULTS: Natural/genetic aetiologies were the most commonly proffered
      (>70%), compared to 19.2% for cancer. Only 8.6% believed in re-incarnation theory
      forSCD. More thaneighty three per cent believed that caring had made family ties
      closer. Though 43.2% felt depressed about patient's condition, 83.9% felt glad
      with caregiving roles, and there was no evidence of stigma from the
      neighbourhood. Only 4.9% had known about possibility of SCD before marriage. Over
      twelve per cent believed that SCD induced inferiority feelings in patient, and
      33.3% that SCD caused lower intelligence. Beliefs and attitudes were not
      significantly correlated with global rating of burden. CONCLUSION: Beliefs about
      aetiology reflect availability of proven knowledge. The caregivers evidenced
      emotional disposition for community psychosocial support roles if they can be
      supported by social welfare and health education.

PMID- 12002067
TI  - Stroke-related mortality at Korle Bu Teaching Hospital, Accra, Ghana.
AB  - OBJECTIVES: To determine whether mortality from and the pattern of stroke have
      changed since the last study in Accra in 1981, the sites of the different types
      of stroke and the role of hypertension and cerebrovascular disease and to
      describe the age and sex distribution. DESIGN: Cross-sectional study of fatal
      stroke cases over a five-year period. SETTING: Korle Bu Teaching Hospital, Accra,
      Ghana. SUBJECTS: All fatal strokes in persons aged 20 years and above, confirmed
      at autopsy. RESULTS: Mortality from stroke constituted eleven per cent of
      autopsies carried out at the Korle Bu Teaching Hospital, Accra, in the five-year
      period 1994 to 1998. A similar study in 1981 showed the same proportion
      indicating that the proportion of deaths due to stroke has not changed. The
      overall male to female ratio was 1.2:1 but the relative risk (RR) of death from
      stroke was higher for females at 1.23 (95% CI=1.10-1.38). Although haemorrhagic
      stroke was still more common than cerebral infarction the proportion (61 %) was
      much less than that of the previous study (89%). Males were more likely (RR 2.07
      95% CI=1.75-2.45) to die from haemorrhagic stroke than females (RR 1.32, 95%
      CI=1.10-1.57). Sixty nine per cent of stroke patients died in less than 24 hours
      after onset of stroke. The peak age of fatal haemorrhagic stroke was 50-59 years
      and that of infarction was 60-69 years. Male mortality exceeded female mortality
      in all age groups up to 60-69 years after which female mortality became
      preponderant (chi2 with Yates correction = 4.28,0.05>p<0.02). Hypertension was
      the dominant factor in haemorrhage and an important factor in infarction while
      cerebral atherosclerosis was the major factor in infarction. Haemorrhage into
      intraparenchymal sites, mainly the cerebral hemispheres, was more common than
      into the subarachnoid space. CONCLUSION: The proportion of deaths from stroke in
      autopsy cases has not changed since the last study in 1981 and stroke still
      remains an important cause of death in Accra. Cerebral haemorrhage is still a
      more common cause of fatal stroke than infarction, although the pattern appears
      to be changing gradually. Females have a slightly greater risk of dying from
      stroke than males. A community-based study is needed to provide more insight into
      some aspects of the problem and to provide the basis for appropriate
      interventions and policy, especially with regard to a control of risk factors.

PMID- 12002068
TI  - Coronary arterial vessels in relation to sudden cardiac death: a review.
AB  - OBJECTIVE: To review literature on the coronary vascular factors related to the
      syndrome of sudden cardiac death. DATA SOURCE/SYNTHESIS: Major published articles
      and case reports on the nature of sudden cardiac death were searched
      electronically (Medline, Internet) and through hand scanning. Comparison of the
      different studies with regard to common themes was undertaken and consensus
      opinions highlighted. RESULTS: The aetiology of sudden cardiac death is diverse.
      Many conditions, hitherto considered benign, including coronary arterial
      anomalies and muscle bridges have been shown to cause sudden cardiac death.
      Coronary atherosclerosis, hypoplastic coronary vessels, coronary artery
      dissections are the commoner causes. The role of coronary arterial thrombi is
      controversial. The protective role of exercise is seriously questioned by the
      many reports of sudden cardiac death in long distance runners. CONCLUSION: Cases
      of sudden cardiac death are increasingly being reported. As a minimum, autopsy
      worksheets for cases of sudden death should include atherosclerosis, congenital
      coronary anomalies, tunneling of coronary vessels and hyposplastic vessels in
      addition to valvular and myocardial disorders.

PMID- 12002069
TI  - Traditional mental health practitioners in Kwara State, Nigeria.
AB  - OBJECTIVES: To assess the knowledge, practice and attitude of traditional mental
      health practitioners (TMHPs) in four Local Government Areas (LGAs) in Kwara
      State, Nigeria, on mental health care; to organise training sessions aimed at
      improving their knowledge base, practice and; to evaluate such training after
      allowing for a period of practice. STUDY DESIGN/INTERVENTION: Pre-training
      evaluation phase: TMHPs were assessed in the area of knowledge, attitude and
      practice of mental health, with the use of a questionnaire. They were then
      trained in the concepts of normality and abnormality, types of mental illness,
      treatment of mental illness including follow up, after-care, relapse prevention,
      other primary preventive measures, and some introductory talks on some sub
      specialties of psychiatry, for example, child psychiatry, old age psychiatry,
      forensic psychiatry, drug and alcohol abuse and; after a free-practice period of
      two months, the TMHPs were again reassessed for the impact of the training.
      RESULTS: Pre-intervention phase: TMHPs could easily recognise most symptoms of
      mental illness except undue sadness. The TMHPs also expressed strong belief in
      the supernatural factor as a cause of mental illness. Some of them beat their
      patients for therapeutic reasons and; Post-intervention phase: there was a
      widening of the sense of recognition of TMHPs of important mental symptoms such
      as undue sadness, social withdrawal and elation. There was a better understanding
      of the aetiological concepts of mental illness. There was also a reduction in the
      habit of beating their patients as a form of treatment. CONCLUSIONS: The use of
      information, education and communication intervention techniques could lead to
      more positive and less hazardous forms of practice among TMHPs and; The high
      level of cooperation achieved in this study would indicate a bright chance for
      future collaborative activities between orthodox and traditional healthcare
      providers.

PMID- 12002070
TI  - Tuberculosis of the spine in Ilorin, Nigeria.
AB  - BACKGROUND: Data on tuberculosis (TB) of the spine from Nigeria is scanty despite
      the endemicity of the disease. OBJECTIVE: To highlight hospital data on spinal
      tuberculosis. DESIGN: A ten-year retrospective study of records on spinal TB from
      the medical records, orthopaedic and medical wards was done. The clinical notes,
      radiographs and haematology results of the patients were analysed. SETTING:
      University of Ilorin Teaching Hospital, Ilorin, Nigeria. SUBJECTS: All patients
      treated for spinal TB in the hospital from January 1990 to December 1999 were
      studied. RESULTS: Fifty patients were seen, 24 males and 26 females, age range
      1.5-70 years (mean 27.1 +/- 22.8 years). Peak prevalence (30%) was in the first
      decade. Twenty seven patients had complete clinical data in their case notes.
      Twelve patients had paraplegia and three had concomitant pulmonary TB. The lumbar
      spine was the commonest site of involvement. Two thirds (18 patients) had
      positive mantoux test. Twenty three patients had chemotherapy but a third was
      lost to follow up within two months. Twenty one patients (77.8%) had difficulty
      obtaining the prescribed drugs due to financial difficulties. No patient had
      surgical intervention. CONCLUSION: Spinal TB is still a common disease in Nigeria
      with unacceptable laxity in control measures. There is need for patient health
      education, contact tracing, provision of free anti-TB drugs and a general
      improvement in the economy to reduce the prevalence of spinal TB in the country.

PMID- 12002071
TI  - Hypodontia of permanent teeth in a Kenyan population.
AB  - OBJECTIVE: To assess the occurrence of hypodontia (except 3rd molars) in a
      population of orthodontic patients. DESIGN: A retrospective case study. SETTING:
      Private orthodontic practice in Nairobi PATIENTS: Six hundred and fifteen
      orthodontic patients aged eight to fifteen years. RESULTS: Hypodontia occurred in
      39 children (6.3%). The missing teeth were observed in 24 males (7.2%) and 15
      females (5.3%). Of the children with hypodontia, about 80% lacked one or two
      teeth, 54% had hypodontia involving anterior teeth, 18% lacked single posterior
      teeth and 8% had two or more teeth missing in the same quadrant. The highest
      recorded number of missing teeth in any one individual was seven. The most
      frequently missing teeth were mandibular 2nd premolars (30%), maxillary 2nd
      premolars (24%) and maxillary lateral incisors (22%) in that order. CONCLUSIONS:
      Our data for hypodontia were within the wide range reported in the literature.
      The finding of patients with hypodontia involving the anterior teeth and others
      missing more than two teeth in the same quadrant was an indication of a great
      need for orthodontic treatment. The present findings reiterate the neeed for a
      thorough radiographic evaluation of patients prior to removal of permanent teeth
      for orthodontic reasons.

PMID- 12002072
TI  - How Kenyan physicians treat psychiatric disorders.
AB  - OBJECTIVES: To determine the psychological problems the non-psychiatric doctors
      commonly encounter, the treatment offered and/or referrals made and to determine
      any obstacles met in providing psychiatric treatment or making referrals. DESIGN:
      Cross-sectional survey. SETTING: Kenyatta National Hospital, Nairobi, Kenya.
      SUBJECTS: Doctors working at Kenyatta National Hospital. RESULTS: One hundred and
      thirty (94 males and 36 females) doctors submitted usable questionnaires. Seventy
      eight per cent of the respondents were below 35 years and 57 had less than five
      years experience. The commonest psychiatric disorders seen by doctors were
      anxiety, depression, psychosomatic disorders and organic psychoses similar to
      findings in previous prevalence studies. Drugs therapy with anxiolytics
      antidepressants and antipsychotics were commonly utilised. Brief counselling was
      the verbal form of treatment most commonly used. Referral to mental health
      workers was less often done. Obstacles cited by the doctors were the patients'
      resistance to referral, lack of coordination and insufficient knowledge to treat
      the disorders. CONCLUSION: The doctors recognise that psychiatric disorders are
      common among their patients but they have major obstacles in managing them. These
      findings are discussed and remedial measures suggested.

PMID- 12002073
TI  - Small intestinal volvulus in Southern Ethiopia.
AB  - BACKGROUND: Small intestinal volvulus (SIV) is a common surgical emergency
      encountered in many countries. It was reported as the most common cause of
      intestinal obstruction in the southern part of Ethiopia. OBJECTIVE: This study
      was intended to evaluate the magnitude and treatment outcome of SIV in a rural
      hospital. DESIGN: Retrospective study. SETTING: A rural general hospital with 250
      beds. SUBJECTS: Ninety eight of 235 patients operated on for acute intestinal
      obstruction. There were 88 males and 10 females (age range of 16-65 years).
      INTERVENTION: All patients who were operated on for acute intestinal obstruction
      during 1992-1996 were included. MAIN OUTCOME MEASURES: Age of patients, duration
      of the illness and extent of the bowel involved, treatment, and complications
      were the main outcome measures. RESULTS: Of the 235 patients with acute
      intestinal obstruction, 98 (41.7%) had SIV. The mean age was 34 years (range 16
      65 years). The male to female ratio was 8.8:1.0. SIV occurred mostly among young
      adults most of whom were farmers. Postoperative complications occurred in 36
      cases. The mortality rate was 13.3%, sepsis being the most frequent cause of
      death. CONCLUSION: Small intestinal volvulus was the leading cause of intestinal
      obstruction in this series. Early diagnosis and prompt operative intervention
      minimises the morbidity and mortality rate.

PMID- 12002074
TI  - Comparative study of haemodynamic responses to active and passive posture
      inducing head-ward pooling of blood in man.
AB  - OBJECTIVE: To study the relative effects of passive head-down tilt and squatting
      on the cardiovascular dynamics in man. DESIGN: A pre-test/post-test study.
      SETTING: Physiology Research Laboratories in the Schools of Medicine at Addis
      Ababa University and the University of Dundee, UK. SUBJECTS: Ten normal healthy
      subjects aged nineteen to twenty two years. INTERVENTION: Cardiovascular
      variables measured in Passive body tilt and squatting. MAIN OUTCOME MEASURES:
      Similar responses in forearm blood flow, arterial blood pressure, peripheral
      vascular resistance, and pulse rate observed in both active and passive postural
      changes. RESULTS: A change from the sitting to the squatting position resulted in
      marked changes of forearm blood flow (FBF=1.63ml/100 ml/min, p<0.05), mean
      arterial blood pressure (BP=9mmHg, p<0.05), mean forearm vascular resistance
      (PVR=-10 PRU, p<0.05) and mean pulse rate (PR =-5 beats/min, p>0.05). The
      corresponding changes in the head-down position were: FBF=2.37ml/100 ml/min,
      p<0.05; BP=11.0 mmHg, p<0.05; VR=-12.85 PRU, p<0.05; PR=-10 beats/min, p>0.05).
      CONCLUSION: These results suggest that the movement of blood towards the head is
      only slightly more marked in the head-down tilt than in the squatting position.
      The changes in flow and arterial blood pressure are similarly correlated
      (r=0.6291 in squatting and r=0.553 in 30 degrees head-down tilt). In both
      positions, blood moves to the thorax, neck and the head thus traversing the same
      baroreflex regions. This means that changes in cardiovascular variables in the
      two positions are detected by the same receptors signalling information to
      integrating centres via the same afferent pathways. Squatting and head-down tilt
      can, therefore, be used alternately to counteract orthostatic dizziness and to
      assess the significance of cardiovascular autonomic neuropathy in patients with
      disease conditions like diabetes mellitus.

PMID- 12002075
TI  - Laparoscopic herniorrhaphy: preference rate among surgeons in Ankara, Turkey.
AB  - OBJECTIVE: To determine the surgeons' and the surgical residents' choice for
      inguinal hernia repair. DESIGN: A questionnaire study. SUBJECTS: One hundred and
      forty two respondents who work in surgical clinics as surgeons or residents.
      SETTING: University hospitals and non-academic teaching hospitals in Ankara,
      Turkey. MAIN OUTCOME MEASURE: The preference rates of open and laparoscopic
      hernia repairs for respondents' own inguinal hernias: "If you had an inguinal
      hernia, how would you prefer to have it repaired?" RESULTS: Only 14.1% of the
      respondents preferred a laparoscopic hernia repair. Eight of 63 residents (12.7%)
      and 12 of 79 surgeons (15.2%) chose laparoscopic technique for their own hernia
      (p=0.67). Personal laparoscopic herniorrhaphy experience significantly affected
      the choice. Among 118 respondents who had performed no laparoscopic hernia
      repair, only 12 (10.2%) preferred laparoscopic technique for their own inguinal
      hernias, whereas the preference rate rose to 33.3% in other 24 participants who
      had previously done laparoscopic hernia repair (p=0.03). The only independent
      variable in multivariate analysis was personal experience on laparoscopic
      herniorrhaphy (SE:0.33, Wald 11.73, Sig:0.0006). The majority of the respondents
      who preferred open hernia repair stated that it was a better known technique.
      Other common reasons for open repair were being better repair and the advantage
      of local anesthesia. Top three reasons for choosing laparoscopic hernia repair
      were less pain, short hospital stay and early return to normal activity.
      CONCLUSION: Majority of surgeons and residents still prefer open hernia repair.

PMID- 12002076
TI  - Patients' attitudes to wearing of gloves by dentists in Nigeria.
AB  - OBJECTIVE: To evaluate patient's attitudes to the use of gloves by dentists.
      DESIGN: This consisted of a four-item questionnaire administered to 445
      consecutive patients attending our dental clinic. SETTING: . Obafemi Awolowo
      University Teaching Hospitals' Complex, Ile-Ife, Nigeria. SUBJECTS: Four hundred
      and forty five patients above the age of fifteen years attending the dental
      clinic for the first time. RESULTS: Majority of the patients were in the 20-30
      year age group and over 93% had formal education. Most of the respondents (88.8%)
      stated that glove wearing was essential and over 63% considered that glove
      wearing protected both the operator and the patient. Whilst about one-third of
      respondents would attend for treatment when gloves were not worn, 81.3% felt that
      gloves should be changed after each patient. There were statistically significant
      differences (p<0.05) in responses in relation to age-groups and educational
      attainment, however no sex differences (p>0.05) were reported. CONCLUSION: This
      survey showed a high level of awareness by patients on the use of gloves by
      dentists. It also found that age-groups and levels of educational attainment
      influenced patients attitude to glove use.

PMID- 12002077
TI  - Hydroquinone neuropathy following use of skin bleaching creams: case report.
AB  - A 30-year old black woman presented with gradual onset of weakness of the legs
      associated with burning sensation in the feet for two months. She had been using
      two hydroquinone based skin bleaching creams (MGC by M. G. C. International,
      MEKAKO by Anglo Fabrics BOLTON Ltd) for about four years. Her BP was 80/40 mm Hg
      supine with un-recordable diastolic pressure on standing. She had decreased power
      (Grade 3/5), loss of deep tendon reflexes and impairment of deep sensation in the
      lower limbs. A complete blood count, urinalysis, serum electrolytes, serum
      creatinine and uric acid were all normal. Oral GTT, VDRL and brucella tests were
      negative. Chest and abdominal radiographs did not show any abnormalities. A
      diagnosis of peripheral neuropathy with autonomic neuropathy possibly due to
      hydroquinone toxicity was made and she was advised to stop using hydroquinone
      based skin bleaching creams. Four months later she was asymptomatic, her BP was
      120/80 mmHg supine and standing, and neurological examination was normal. The
      case raises the question of whether hydroquinone based skin bleaching creams
      could be a cause of peripheral neuropathy and underscores the need for research
      on hydroquinone based skin bleaching creams and neuropathy particularly in black
      women involved in the sale and/or use of skin bleaching creams.

PMID- 12002078
TI  - Role of fine needle aspiration in the diagnosis of neoplasms.

PMID- 12002079
TI  - Comparison of fine-needle aspiration cytology and excisional biopsy of breast
      lesions.
AB  - OBJECTIVES: To evaluate the sensitivity and specificity of fine-needle aspiration
      cytology as compared to excisional biopsy of breast lesions of the same subjects
      and ascertain the usefulness of the method as diagnostic procedure. DESIGN: A
      prospective comparative study of fine-needle, aspiration, cytology and excisional
      biopsy of breast lesions. SUBJECTS: One hundred and two patients with palpable
      breast lesion. RESULTS: Fine-needle aspiration cytology as a routine method in
      the management of breast diseases was compared to excisional biopsy of the same
      patients. Sixteen patients (15.7%) had carcinoma of the breast and 86 (84.3%)
      cases were found to have fibroadenomas of the breast. The sensitivity was 94.3%
      and the specificity was 78.6%. The positive and negative predictive values were
      68.8% and 96.5% respectively. There were three false positive and false negative
      cases. CONCLUSION: The high sensitivity and specificity results, obtained
      ascertains that fine needle aspiration cytology is the most reliable diagnostic
      method. Its cheapness and respectable diagnostic value makes it indispensable for
      preoperative breast lesion diagnosis.

PMID- 12002080
TI  - Histo and cyto-pathologic diagnoses at a rural hospital in Kenya.
AB  - BACKGROUND: Cancer has emerged as one of the common causes of morbidity and
      mortality in rural areas and as a major cause of premature deaths. OBJECTIVES: To
      provide histo-pathology and cyto-pathology data in a rural district hospital and
      highlight on the common malignancies seen in a rural setting in Kenya. DESIGN:
      Prospective study. SETTING: Histopathology Department, Machakos Provincial
      Hospital, Machakos district, Kenya. SUBJECTS: Two hundrend and sixty eight
      patients referred to Machakos laboratory for histopathology, fine needle aspirate
      or pap smear cyto-pathology were analysed. MAIN OUTCOME MEASURES: Staining with
      routine stains such Pap stain, Haeomatoxylin and Eosin was effective method of
      making a primary accurate and definitive histo-pathology and cyto-pathology
      diagnosis in a rural district hospital setting. RESULTS: Histo-pathology biopsies
      comprised 71.6% of the total slides seen. Pap smear cervical cytology comprised
      13.8% while fine needle aspirate and post- mortem biopsies comprised 12.3%, 2.2%
      respectively. The commonest histo-pathology biopsies seen were breast comprising
      24% of the total cases, followed by endometrium contributing 14.9%, then followed
      by skin 11.5%, lymph node 11.5%, cervical 11%, and gastrointestinal 6.3%. Most of
      pap smear cyto-pathology showed evidence of infection comprising 54% while fine
      needle aspirate infections and malignancy showed equal rate 24% of all cyto
      pathology seen during this study. CONCLUSIONS: This is the first time histo
      pathology and cyto-pathology data have been provided from a rural district
      hospital setting in Kenya. The malignant and pre-malignant pattern seen at
      Machakos General Hospital may be used to gain a broader picture of the common
      malignant conditions prevalent in any defined population in this country. This
      also serves as an important cancer epidemiological data in this region during the
      period of study.

PMID- 12002081
TI  - Management of cancer of the stomach in Mulago Hospital Kampala, Uganda.
AB  - OBJECTIVE: To determine the clinical presentation, mode of investigation and
      management of gastric cancer at New Mulago Hospital. DESIGN: Prospective
      descriptive study. SETTINGS: Three general surgical wards, Department of Surgery,
      New Mulago Hospital. SUBJECTS: Thirty five patients were studied within 12
      months. RESULTS: Gastric cancer was found to be prevalent in tribes inhabiting
      volcanic areas of south western Uganda especially the Banyankole (25%). The
      commonest mode of clinical presentation was epigastric pain, weight loss,
      constipation, epigastric tenderness, palpable epigastric mass and anaemia. The
      most accurate mode of investigation was by endoscopy followed by barium meal. The
      commonest locality was the pyloric atrium (40%) histologically adenocarcinoma
      (95.5%) predominated. Gastric cancer was found to be more common in patients with
      blood group O+ve. All patients had been subjected to some kind of medical
      treatment especially with antiacids, H2 receptor antagonists which contributed to
      the delay in presentation. The majority of patients (94.5%) presented with
      advanced disease and no curative surgery was possible. CONCLUSIONS: These results
      show that early diagnosis of gastric cancer is still a dream at Mulago hospital
      since most patients present with advanced disease. To address this problem, all
      health workers should be sensitised on symptoms and signs for early aggressive
      investigation or an early referral to enable early diagnosis of gastric cancer.
      The investigatory capacity of rural hospitals should be boosted to enable early
      detection of gastric cancer.

PMID- 12002082
TI  - Factors influencing the outcome of severe head injury at Kenyatta National
      Hospital.
AB  - OBJECTIVE: To study the factors influencing the outcome of severe head injury.
      DESIGN: A retrospective study. SETTING: Kenyatta National Hospital, Nairobi,
      Kenya. SUBJECTS: Six hundred and seventy seven patients with severe head injuries
      who were seen at Kenyatta National Hospital between January 1992 and December
      1996. RESULTS: Six hundred and seventy seven patients with severe head injuries
      were treated at Kenyatta National Hospital, between January 1992 and December
      1996. Three hundred and eighty one patients died while undergoing treatment,
      56.2% overall mortality. Age specific mortality was 35.7% in patients below 13
      years, 44% in age group 14-25 years, 56% in age group 26-45 years. The admission
      Glasgow coma scale (GCS) was recorded in 637 patients. Patients with admission
      GCS of 3-4 had a mortality of 88%, those with GCS 5-6 had a mortality of 60% and
      those with admission GCS 7-8 had a mortality of 52%. Ninety per cent of the
      patients who had bilaterally dilated pupils not reacting to light on admission
      died and 66% of the patients with bilaterally constricted pupils at the time of
      admission died. Only 20% of patients with severe head injury who had normal
      pupillary reaction to light at the time of admission died. Eighty five per cent
      of the patients with systolic BP of less than 90 mmHg on admission died while 60%
      of those with systolic BP greater than 120 mmHg died. CONCLUSION: In this study,
      factors associated with poor outcome in severe head injury patients at Kenyatta
      National Hospital were age, admission GCS, admission blood pressure (systolic),
      presence of other associated injuries and pupillary reaction to light.

PMID- 12002083
TI  - Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa.
AB  - BACKGROUND: Western literature depicts papillary carcinoma as the most common
      thyroid malignancy followed by follicular carcinoma. OBJECTIVE: To assess the
      clinical pattern of thyroid carcinoma among African and Indian patients. SETTING:
      King Edward VIII Hospital, Durban, South Africa. DESIGN: A retrospective study.
      SUBJECTS: One hundred patients with thyroid carcinoma treated at a tertiary
      teaching hospital between 1990 and 1997. RESULTS: Seventy seven patients were
      Africans and 23 were Indians. The male to female ratio was 1:6. Ninety eight
      patients presented with goitre with or without regional lymph node involvement or
      distant disease. The duration of symptoms ranged from one to 360 months. The mean
      age at presentation was 48.6 +/- 16.0 years. Follicular carcinoma was the most
      common malignancy among African patients (68%), followed by papillary carcinoma
      (16%), anaplastic carcinoma (13%) and medullary carcinoma (2.6%). Papillary
      carcinoma was the most common malignancy among Indian patients (57%) followed by
      follicular carcinoma and medullary carcinoma. There was no anaplastic carcinoma
      among Indian patients. Fifty five patients underwent lobectomy with 32 undergoing
      subsequent completion thyroidectomy. Nine patients had near total thyroidectomy,
      27 were offered total thyroidectomy as primary surgery and eight had biopsy only.
      The in-hospital mortality was 8%. Recurrence rate was 8%. CONCLUSION: Most
      patients present long after the development of symptoms. Follicular carcinoma is
      the most common thyroid malignancy among Africans. Further studies are required
      to explain this phenomenon.

PMID- 12002084
TI  - Iron deficiency in rural Ghanaian children.
AB  - OBJECTIVES: To compare the prevalence of iron deficiency among Ghanaian children
      in different residential settings and to see whether 200mg ferrous fumerate B.P.
      could correct iron deficiency anaemia in observed cases of iron deficiency.
      DESIGN: Prospective case-finding study using an iron-deficiency society
      questionnaire, laboratory data and general practice records. Crude prevalence was
      calculated using the hospital's mid-year estimates. SETTING: Nkoranza in the
      Brong Ahafo Region of Ghana, Komfo Anokye Teaching Hospital, Kumasi, Ghana
      SUBJECTS: Rural-dwelling children entering as out-patients, urban-dwelling
      children entering as controls and newly diagnosed iron-deficient children
      entering as in-patients. MAIN OUTCOME MEASURES: Crude prevalence rates (per
      quinquennia) for three groups of children. Corrected deficiencies expressed as
      percentage after management. Age, haemoglobin, iron status, residential status,
      symptoms at entry and after therapy. RESULTS: Following a 30-day administration
      of ferrous fumarate, the mean serum iron for the rural children increased
      significantly by 3.3 micromol/l representing an improved iron status of
      20.0%(P<0.0001). Iron deficiency anaemia defined by serum Hb<12.0 g/dl and
      Fe<12.5 mmol/l decreased by 10% in the rural subjects. Comparatively, iron
      deficiency among the newly diagnosed anaemia group, fell by 17.6% whilst their
      ambulant urban counterparts employed as the control group had an iron deficiency
      anaemia of 0.0%. CONCLUSION: The study clearly indicates that the-prevalence of
      iron deficiency anaemia among children in rural Ghana is about ten times that of
      the urban-dwelling children and that iron-deficiency anaemia accounts for a
      greater percentage of all anaemic cases among children in our hospitals. It was
      also shown that taking appropriate iron supplements like 200 mg of ferrous
      fumerate for thirty days can substantially improve the iron status of iron
      deficient children.

PMID- 12002085
TI  - Pattern of ophthalmic lesions at two histopathology centres in Ethiopia.
AB  - OBJECTIVE: To describe the distribution of ocular, orbital and eyelid lesions
      that required histopathologic analysis in Ethiopian children and adults. DESIGN:
      A retrospective study. SETTING: Tikur Anbessa and Menelik II Teaching hospitals,
      Addis Ababa, Ethiopia, during 1995 and 1999 period. RESULTS: Two hundred and
      ninety ophthalmic specimens were examined, 20% of which came from children. Half
      of the lesions had epithelial origin, about 30% were malignant, 22.6% were benign
      and 16.4% were potentially malignant. Squamous cell carcinoma was the leading
      conjunctival (26%), eyelid (33%), orbital (33%) and ocular (20%) lesion among
      adults and elderly people whereas only 6% of eyelid lesion were basal cell
      carcinomas. In children the most frequent intra-ocular as well as orbital tumour
      was retinoblastoma, 39%, followed by miscellaneous benign lesions (24%). More
      than half of the request forms were incomplete. CONCLUSIONS: In Addis Ababa,
      squamous cell carcinoma and retinoblastoma should be considered when evaluating
      ophthalmic lesions in adults and children, respectively. Clinicians and
      pathologists should improve their communication by filling in request forms,
      providing clear reports and making dialogue.

PMID- 12002086
TI  - Impact of female genital mutilation on maternal and neonatal outcomes during
      parturition.
AB  - OBJECTIVE: To evaluate the impact of female genital mutilation on parturition and
      to create awareness of its implication on women and neonatal health. DESIGN: A
      cross-sectional study. SETTING: Tikur Anbessa, St. Paul's and Ghandhi Memorial
      hospitals between January and December 1997. SUBJECTS: One thousand two hundred
      and twenty five mothers with and 256 without FGM who have had spontaneous, term,
      singleton and vertex vaginal delivery. Of these, 762 (51.5%) were primipara and
      719 (48.5%) of them multipara. The parameters focussed upon included age,
      ethnicity, parity, type of circumcision, episiotomy, stages of labour, Apgar
      scores and related complications. RESULTS: The study revealed that 82.7% of the
      subjects had one form of FGM. The mean ages for the circumcised and non
      circumcised were 25.9 +/- 5.9 and 21.8 +/- 4.5 years, respectively. The
      frequently performed genital mutilation was type II (85.5%). The mothers who
      required an episiotomy incision for foetal and maternal indications among the
      circumcised accounted for 43.0% whereas it was only 24.6% for the referent group.
      The mean duration of labour by conventional standards is prolonged in primiparae
      and multiparae both in the circumcised and non-circumcised groups, though the
      second stage is delayed more so for the circumcised category (p<0.05). The first
      and tenth minute mean Apgar scores seem to be more favourable for the non
      circumcised (p<0.05) but the perinatal mortality rates are quite similar. More
      complications in terms of perineal tears, bleeding, incontinence and febrile
      illnesses are registered for the FGM. CONCLUSION: The study demonstrates the
      negative impact of FGM more on maternal than neonatal outcomes during
      parturition.

PMID- 12002087
TI  - Antimicrobial sensitivity of Neisseria gonorrhoea in Gondar, Ethiopia.
AB  - OBJECTIVES: To determine the antimicrobial susceptibility pattern of Neisseria
      gonorrheae and to obtain epidemiological information on resistance of Neisseria
      gonorrheae in Gondar town. DESIGN: A cross sectional study. SETTING: Gondar
      Health Centre. SUBJECTS: One hundred and seventy eight male patients presented
      with urethral discharge and who volunteered to participate in the study were
      included. RESULTS: A total of 142 strains of N. gonorrhoeae were isolated from
      168 cultures received. The sensitivity of gonococcal isolates ranges from 98.6%
      to chloramphenicol to 7.7% to cotrimoxazole. Multiple drug resistance was
      reported in 87.5% of isolates and only four isolates were sensitive to all
      antibiotics. One strain of N. gonorrheae was resistant to as many as eight
      antibiotics (tetracycline, penicillin, ampicillin, kanamicin, methicilin,
      carbenicillin, cotrimoxazole and ceftriaxone). More than eighty five per cent of
      the isolated strains were penicillinase-producing Neisseria gonorrhoeae (PPNG).
      CONCLUSION: Gonococcal resistance is a significant public health problem in
      Gondar region and the drugs recommended for treatment of gonococcal cases by the
      national sexually transmitted diseases (STDs) control programme need to be
      revised.

PMID- 12002088
TI  - Emergency obstetric referrals at a university teaching hospital, Nigeria.
AB  - OBJECTIVE: To identify factors in our unbooked obstetric emergency cases that
      contribute to the increase in maternal mortality. DESIGN: A retrospective study.
      SETTING: Maternity Ward, University of Nigeria Teaching Hospital, Enugu, Nigeria,
      between January 1966 and December 1999. SUBJECTS: Four hundred and thirty five
      cases of emergency obstetric referrals treated during the review period. RESULTS:
      The incidence of unbooked obstetric emergencies is 9.5% and the high risk
      obstetric group, the primigravida and grand multiparous women constituted 63% of
      it. Majority (80%) of the patients belonged to the lower socio-economic class and
      prolonged and obstructed labour were the commonest mode of presentation. Sources
      of referrals were hospital/clinics (46%), maternity homes (23%), traditional
      birth attendants (TBAs)(16%) and prayer houses (2.3%). There were obvious delays
      at the referral sources and most of the patients presented in poor clinical
      states. Forty per cent of total maternal mortality in the hospital were
      attributed to unbooked cases with haemorrhage and sepsis being the major causes.
      Also perinatal mortality of 40.2% was recorded. CONCLUSION: Lack of basic
      education and poverty are the major identifiable risk factors. Improving health
      care facilities, female education, regular training courses for medical personnel
      and elimination of quacks are advocated.

PMID- 12002089
TI  - Abortion at Gondar College Hospital, Ethiopia.
AB  - OBJECTIVE: To review the pattern and magnitude of abortion in order to establish
      baseline facts and data for future studies. DESIGN: A descriptive cross-sectional
      study. SETTING: Gondar College of Medical Sciences Hospital, Gondar, Ethiopia.
      RESULTS: Most of the subjects originated from the Gondar city and were married
      housewives, parous and relatively young. The abortion rate and ratio per 100
      pregnancies and deliveries were 11.5 and 16.4, respectively. Only 13.4% of the
      patients admitted history of interference with the pregnancy. Previous history of
      abortion was obtained in 10.6% of the patients. The mean gestational ages for
      septic and non-septic cases were 14.6 and 15.2 weeks, respectively even though
      pregnancies less than 12 weeks from the last normal menstrual period accounted
      for 50.5%. The commonly diagnosed clinical type was incomplete, followed by
      inevitable and threatened abortion. The vast majority of the clinical conditions
      were non-septic (85.1 %) and spontaneous(85.6 %). The most common complications
      registered were anaemia, genital tract infection, shock of various causes and
      soft tissue injury. Four mothers died of abortion-related complications. The mean
      hospital stays for non-septic and septic abortion were three and five days,
      respectively. CONCLUSION: The study has attempted to address the issue of
      abortion in its general clinical pattern in relation to the various parameters.
      Being comprehensive, it also provides awareness and sensitivity on the magnitude
      of abortion and is assumed quite helpful for policy and decision makers.

PMID- 12002090
TI  - Obsessive compulsive disorder: report of six cases.
AB  - Obsessive-compulsive disorder (OCD) refers to interloping and interative
      thoughts, ideas, images, fantasies, impulses and actions accompanied by feelings
      of distress and declarations of resistance. It is assumed that OCD is rare among
      black Africans. This paper reports six cases from Uganda. The report indicates
      that OCD exists among black Africans and that those affected experience
      considerable amounts of emotional, social and occupational distress. It is
      suggested that OCD should be taught adequately to medical students to enable
      future general-duty medical officers to recognise and manage it appropriately.
      The names that appear in the text are pseudonyms.

PMID- 12002091
TI  - Collagenous colitis in an adult patient with chronic diarrhoea: case report.
AB  - Collagenous colitis is an established cause of chronic watery diarrhoea of
      unknown aetiopathogenesis, characterised by normal colonic endoscopic findings,
      and a prominent collagen band in the sub-epithelial layer on colonic mucosal
      histology. We report a case of a 65-year old male who presented with recurrent
      episodes of watery diarrhoea of 38 years duration. There was a positive family
      history of similar diarrhoea in the mother and two siblings. Colonoscopy done was
      macroscopically unremarkable except for a redundant sigmoid colon. Mucosal biopsy
      of the rectum and colon showed at histology atrophy of the mucosal lining,
      infiltration of the lamina propria by plasma cells and lymphocytes, and a thick
      band of collagenous tissue in the sub-epithelial zone of the lining mucosa. A
      high index of suspicion is necessary to make the diagnosis in patients with
      chronic diarrhoea, especially when common causes of chronic diarrhoea like
      intestinal parasitoses, HIV/AIDS, diabetic autonomic neuropathy, thyrotoxicosis
      have been excluded. It is suggested that colonoscopic examination with adequate
      biopsy should be performed in patients with chronic diarrhoea with no aetiologic
      agent identified.

PMID- 12002092
TI  - Toxoplasma encephalitis in HIV: case report.
AB  - In Tanzania, no data are available on the prevalence of brain infection by
      toxoplasma in HIV-infected patients. A case of a 35-year old man with fulminant
      toxoplasma encephalitis (TE) is reported for the first time. TE was not suspected
      clinically in our patient who presented with a one week history of severe
      headache and treated empirically with antimalarial drugs. TE was diagnosed
      postmortem histologically by haematoxylin-eosin and immunohistochemical stain
      with P30 antibody for toxoplasma antigen. The findings in our case support the
      suggestion that a high index of suspicion for TE should be maintained in HIV
      infected patients presenting with focal neurological symptoms. The case
      highlights the importance of autopsy studies in not only documenting a toxoplasma
      brain lesion but also in increasing the awareness for its diagnosis in HIV
      infected patients in Tanzania and other developing countries.

PMID- 12002093
TI  - Effect of low levels of serum vitamin B12 and folic acid on cognitive performance
      in old age: a population-based study.
AB  - We studied the effect of low levels of vitamin B12 and folic acid, alone or
      combined, on cognitive performance in a population-based sample of 698 older
      adults (mean age = 68.7 years). No evidence was found for a vitamin-related
      memory deficit, but research participants with low levels of vitamin B12
      exhibited reduced information processing speed relative to participants with
      normal vitamin B12 levels.

PMID- 12002094
TI  - The Flexible Item Selection Task (FIST): a measure of executive function in
      preschoolers.
AB  - Abstraction and cognitive flexibility were assessed in 197 preschool children at
      2, 3, 4, and 5 years of age using the Flexible Item Selection Task, a task
      adapted from the Visual-Verbal Test (Feldman & Drasgow, 1951). On this new
      inductive task, children were shown a set of 3 cards and required to select 2
      cards that matched each other on 1 dimension (Selection 1) and then to select a
      different pair of cards that matched each other on another dimension (Selection
      2). Thus, 1 of the 3 cards always had to be selected twice according to different
      dimensions. Two-year-olds failed to understand basic task requirements as
      assessed by a criterial measure. Three-year-olds did more poorly on Selection 1
      than 4- and 5-year-olds (who performed near ceiling), suggesting that 3-year-olds
      had difficulty with the abstraction component of the task. Four-year-olds did
      worse than 5-year-olds on Selection 2, suggesting that they had difficulty with
      the cognitive flexibility component (i.e., difficulty selecting the same card on
      more than 1 dimension). Results are discussed in terms of the development of
      executive function.

PMID- 12002095
TI  - Children with adequate academic achievement scores referred for evaluation of
      school difficulties: information processing deficiencies.
AB  - Children (7-11 years old) with standardized academic achievement test scores in
      the normal range referred for evaluation of learning problems were compared to
      low-achieving children matched for age, sex, and nonverbal cognitive ability, and
      to children with no known history of learning difficulty matched for age, sex,
      and reading (all N = 65) on a battery of computerized tasks of nonverbal
      information processing. The normally achieving referred children performed
      similarly to the low-achieving group but worse than reading-matched nonreferred
      counterparts. These findings suggest that children who struggle in school yet
      perform adequately on standardized achievement measures can have heightened
      neurodevelopmental vulnerability. Implications are discussed with respect to the
      underlying substrate of learning disabilities, as well as their diagnosis,
      classification, and remediation.

PMID- 12002096
TI  - Familial influences on hand preference: genotypic variation between closely
      related primate species.
AB  - The emergence of hemispheric specialization has important implications for the
      development of higher order cognitive processes, including language and spatial
      skills. In this research we sought to further understand psychobiological
      processes associated with the development of hemispheric specialization by
      examining and comparing familial influences on hand preference in two closely
      related macaque species: rhesus macaques (Macaca mulatta) and pigtailed macaques
      (Macaca nemestrina). The results of our study indicate contrasting patterns of
      familial influence on hand preference in each species. For the rhesus macaque we
      found a positive correlation in the direction of hand preference between mothers
      and their juvenile offspring, and for the pigtailed macaque we found a negative
      mother-offspring correlation in the direction of hand preference. Fathers did not
      contribute significantly to the direction of hand preference in either species.
      There was a trend toward a positive correlation for strength and consistency of
      hand preference between parents and offspring in rhesus macaques but not in
      pigtailed macaques. These findings indicate that maternal influences on offspring
      hand preference vary between closely related primate species and lead us to
      question the generalizability of universal single-factor theories used to explain
      intergenerational transmission of hand preference in humans.

PMID- 12002097
TI  - Event-related potentials and picture-word naming: effects of attention and
      semantic relation for children and adults.
AB  - Event-related potentials (ERPs) were recorded from children, 9 to 13 years of
      age, while they named words and pictures. The words and pictures were presented
      individually and in superimposed picture-word pairs in which the meaning of the
      words and pictures was either congruent, semantically associated, or incongruent.
      Both words and pictures elicited large amplitude negative waves (N450) at
      anterior electrode sites. The amplitude of this N450 wave was larger for
      individually presented pictures than for words. N450 amplitude was also larger
      when naming pictures than when naming words in the superimposed arrays, an effect
      that is attributed to differences in attentional demand required to name pictures
      rather than to exogenous stimulus characteristics. No significant effects of
      semantic incongruity were observed. These ERP waveforms for children differ from
      those observed for adults who exhibited positive amplitude waves to individually
      presented pictures and who also exhibited semantic incongruity effects.

PMID- 12002098
TI  - The effects of maternal depression on fetal heart rate response to vibroacoustic
      stimulation.
AB  - To better understand the effects of untreated maternal depression on the fetus,
      this study examined fetal heart rate (FHR) and FHR reactivity to vibroacoustic
      stimulation in pregnant women with untreated depression. The 20 participants were
      32- to 36-week pregnant women divided into groups with depression (N = 10) and
      without depression (N = 10) based on the Beck Depression Inventory (BDI; Beck,
      1977; Beck & Steer, 1987). Participants were attached to a fetal heart monitor,
      and 10 min of baseline FHR were recorded. A vibroacoustic stimulus (VAS) was
      presented, and an additional 10 min of FHR were recorded. Fetuses of mothers with
      depression had an elevated baseline FHR and a 3.5-fold delay in return to
      baseline FHR after VAS presentation. Additionally, mothers with depression had
      significantly higher anxiety levels and took fewer prenatal vitamins during
      pregnancy. Delayed habituation of FHR in the fetuses of mothers with depression
      may be due to alterations in the internal hormonal environment and could have
      implications for postnatal information processing.

PMID- 12002099
TI  - Inhibitory control across the life span.
AB  - Findings from previous research suggest that inhibitory control improves during
      early childhood and declines during late adulthood. Very few researchers,
      however, have examined life-span changes in this ability in single studies.
      Within this life-span context, we investigated 1 type of inhibitory control--the
      ability to inhibit aprepotent response and generate an incompatible response--in
      individuals ranging from 6 to 82 years of age. Examination of raw reaction time
      data revealed a significantly larger inhibitory control effect for children and
      older adults than for young adults. Using proportional and z score
      transformations, we demonstrated that a processing speed explanation is
      sufficient to account for the differences in performance between children and
      young adults; this explanation, however, did not adequately explain the
      discrepancy between young and older adults. Taken together, these findings
      suggest that, above and beyond differences in processing speed, inhibitory
      control was less efficient in older adults. Our findings are consistent with the
      assertion that inhibitory control develops quite early and declines at the later
      end of the developmental spectrum.

PMID- 12002100
TI  - Parasitic infestation in children.

PMID- 12002101
TI  - Intestinal helminths and schistosomiasis among school children in a rural
      district in Kenya.
AB  - OBJECTIVE: To determine the extent of intestinal schistosomiasis, ascariasis,
      trichuriasis and hookworm infections among school children of Usigu and Bondo
      divisions of Bondo District. DESIGN: A cross sectional study. SETTING: Fifty out
      of 130 primary schools in Usigu and Bondo divisions, Bondo District. SUBJECTS:
      Randomly selected school children (n= 3158) aged five to 20 years, were examined
      for intestinal helminths and schistosomiasis using Kato thick smear technique.
      RESULTS: The overall prevalence and geometric mean egg counts per gram/faeces for
      Schistosoma mansoni were 31.6% and 3.1; hookworm 36.8% and 4.1; Trichuris
      trichiura 21.8% and 1.5, and Ascaris lumbricoides 16.5% and 2.5. More girls
      (34.9%) than boys (28.6%) were infected with S. mansoni whereas more boys (39.0%)
      than girls (34.5%) were infected with hookworm. The prevalence of S. mansoni and
      hookworm infections increased with age but Ascaris and Trichuris infections
      decreased with age without any sex differences. Children under ten years of age
      tended to be more heavily infected with ascariasis, trichuriasis and hookworm
      than the older ones, while the intensity of S. mansoni increased gradually with
      age. There were positive relationships between different infections except for a
      significant negative correlation between Schistosoma mansoni and hookworm
      infections. Only four cases out of 789 had S. haematobium infection. CONCLUSION.
      Schistosoma mansoni and geohelminths were endemic in Bondo District, where two
      thirds of the school children suffered from these parasites. Polyparasitism was
      also common. There was a little overlap in the distribution of Schistosoma
      mansoni and hookworm, whereas ascariasis and trichuriasis were fairly distributed
      in the district.

PMID- 12002102
TI  - Epidemiology of intestinal helminth infestations among schoolchildren in southern
      Uganda.
AB  - OBJECTIVE: To determine the prevalence and intensity of intestinal helminth
      species among school children in southern Uganda. DESIGN: A cross-sectional
      survey using a randomly selected sample. SETTING: Eighteen districts of southern
      Uganda. SUBJECT: Two thousand and four school children aged two to twenty years
      (93.3%, aged 5-10 years) selected from classes 1 and 2 in 26 randomly selected
      primary schools. RESULTS: Overall, 55.9% of children were infected with either
      hookworm, Ascanis lumbricoides or Trichuris trichiura. The prevalence of A.
      lumbricoides was 17.5% ( range 0-66.7% by school), T. trichiura was 7.3% (0
      45.0%) and hookworm 44.5% (15.6-86.0%). The prevalence of A. lumbricoides and T.
      trichiura was greatest in western districts while hookworm infection was more
      evenly distributed across the country. CONCLUSION: Mass antihelminthic treatment
      of school children was warranted in 13 of the 18 districts as more than 50% of
      the children were infected with an intestinal nematode. It is likely that pre
      school children are similarly infected.

PMID- 12002103
TI  - Prevalence and intensity of urinary schistosomiasis in primary school children of
      the Kotto Barombi Health Area, Cameroon.
AB  - OBJECTIVE: To assess the prevalence and intensity of urinary schistosomiasis in
      school pupils aged five to sixteen years. SETTING: Barombi Kotto Health Area,
      southwest Cameroon. DESIGN: A cross-sectional study. SUBJECTS: Three hundred and
      forty seven primary school children. INTERVENTION: All children found to be
      infected were treated with praziquantel (biltricide). MAIN OUTCOME MEASURES: The
      study would be able to provide baseline information on the epidemiology of
      schistosomiasis which is vital for control strategies. RESULTS: The overall
      prevalence of Schistosoma haematobium in the study areas was 53.6%, with the
      highest prevalence of 73.9% recorded in Barombi Kotto village. Children resident
      on Barombi Kotto island were more significantly infected than those on the
      peripheral mainland (93.3% versus 46.2%, p < 0.01). Prevalence rate and intensity
      of infection did not vary significantly (p > 0.05) with sex, class or age of the
      pupils. The mean egg count varied significantly between schools (p < 0.001).
      CONCLUSION: Barombi Kotto village was identified as the focus of urinary
      schistosomiasis, with the highest recorded in children dwelling on the island,
      the surrounding lake being the main focus of transmission. Focal snail control as
      an adjunct of chemotherapy and intensive health education for the local
      population are strongly recommended as a means of reducing the high infection
      rate in the area.

PMID- 12002104
TI  - Provision of removable denture prosthesis at a university teaching hospital in
      Kenya.
AB  - OBJECTIVE: To compile an audit of removable denture prosthesis fabricated for
      patients attending a teaching clinic. DESIGN: A retrospective analysis. SETTING:
      Division of Prosthetic Dentistry, Faculty of Dental Sciences, University of
      Nairobi, Nairobi, Kenya. METHOD: Clinical records of the patients attended to in
      the prosthetic teaching clinic from 1993 to 1997 inclusive were analysed to
      extract information regarding the quality of clinical notes and the pattern of
      provision of prostheses. RESULTS: A total of 817 patients were provided with
      dentures of whom 602 were provided with complete upper and lower dentures. Single
      complete dentures were fabricated for 18 patients and 197 patients had partial
      dentures fabricated. CONCLUSION: While the number of prostheses provided may be
      in conformity with the unit resources, clinical notes were found to have
      significant omissions for which recommendations have been suggested.

PMID- 12002105
TI  - Childhood poisoning at the Queen Elizabeth Central Hospital, Blantyre, Malawi.
AB  - OBJECTIVES: To record the number of children with poisoning admitted to the Queen
      Elizabeth Central Hospital over one year; to note the causes, clinical and
      laboratory findings and outcome of each poisoning event and; to highlight any
      preventable pattern in such events. DESIGN: A one year prospective study was
      undertaken of all children admitted to the Queen Elizabeth Central Hospital with
      a history or clinical evidence of acute poisoning. Socio-demographic, clinical
      and laboratory data were recorded and outcome noted for each child on specially
      prepared forms. Data were entered and then analysed in Epi-Info 6. SETTING:
      Department of Paediatrics, Queen Elizabeth Central Hospital, Blantyre, Malawi.
      INTERVENTIONS: Children were treated forpoisoning according to national
      guidelines; supportive care and active antidote were given as necessary. MAIN
      OUTCOME MEASURES: Length of stay in hospital and mortality were primary outcome
      measures. RESULTS: One hundred and forty four cases were admitted, 118 (82%) were
      accidental, in 19 cases the reason was unknown and six (4.2%) were non
      accidental. Carbonate poisoning caused 32% (n=46) of admissions and paraffin
      16.7% (n=24). The age range of poisoned children was three weeks to 14 years with
      a mean of four years and eight months. Eleven deaths occurred, six of which were
      due to traditional medicine intoxication. CONCLUSION: Most poisoning were
      preventable and the public needs to be made aware of the dangers of household
      agents, advised how to store them in the home and what to do if a child ingests a
      poisonous substance. Traditional medicines are particularly dangerous to give to
      infants less than one year old and carry a high mortality.

PMID- 12002106
TI  - Antibiotic resistance and sero-groups of shigella among paediatric out-patients
      in southwest Ethiopia.
AB  - OBJECTIVE: To determine the prevalence of Shigella sero-groups and resistance
      pattern of isolates to commonly used antibiotics in Jimma. DESIGN: Cross
      sectional survey. SETTING: The study was conducted in Jimma, southwest Ethiopia.
      SUBJECTS: A total of 384 paediatric out-patients with diarrhoea aged 14 years and
      below were studied. METHODS: Stool specimens were collected from children
      presenting with diarrhoea using Cary-Blair transport medium and buffer treated
      swabs from Jimma hospital and Jimma health centre. Isolation, biochemical
      characterisation, sero-grouping and antibiotic sensitivity testing were performed
      according to standard methodology in the Microbiology laboratory of Jimma
      University. RESULTS: Out of the 77 Shigella strains isolated, sero-group A
      comprised 29.9%, B 40.3%, C 19.5% and D 10.4%. Among all Shigella sero-groups,
      highest resistance was encountered to tetracycline (63.6%), ampicillin (70.1%),
      cephalothin (57.1%), trimethoprim-sulphamethoxazole (32.5%) and chloramphenicol
      (40.3%) whileleast resistance was observed to gentamicin (1.3%), polymyxin B
      (3.9%) and nalidixic acid (6.5%). CONCLUSION: Gentamicin, polymyxin B and
      nalidixic acid were found to be the drugs of choice for cases related with
      shigellosis.

PMID- 12002107
TI  - Foamy and sea-blue histiocytes in a child.

PMID- 12002108
TI  - Health services utilisation among secondary school students in Arusha region,
      Tanzania.
AB  - OBJECTIVE: To investigate patterns and determinants of health services
      utilisation by secondary school students. DESIGN: A cross-sectional survey.
      SETTING: Twelve secondary schools located within seven districts of Arusha region
      Tanzania. PARTICIPANTS: Three thousand six hundred and three students
      proportionately selected from the twelve schools according to enrolment size.
      MAIN OUTCOME MEASURES: Self-reported use of modern and traditional health
      services within the past two years. RESULTS: The majority (77%) of the students
      used only modern health services while very few (1.3%) used only traditional
      services. Fever was the main reason for seeking health care during the last
      visit. Respondents who used traditional services expressed lower level of
      satisfaction with the services than those who used modern services. Living
      situation and socio-economic status of respondent's family predicted utilisation
      of modern health services whereas self-rated health status and perception that
      poverty was a threat against one's health predicted utilisation of traditional
      health services. CONCLUSIONS: Since most of secondary school students use modern
      health services, improvement of the modern health system is likely to benefit
      this population. Further work is needed to elucidate factors that facilitate or
      impede use of health services by young people in Tanzania.

PMID- 12002109
TI  - Prevalence of mental and behavioural disorders in Ethiopian children.
AB  - OBJECTIVE: To determine the magnitude of specific mental and behavioural
      disorders in children in Butajira, southern Ethiopia. DESIGN: A cross-sectional
      survey. SETTING: Butajira district, southern Ethiopia. SUBJECTS: Amharic version
      of the diagnostic instrument for children and adolescents was used to interview
      parents of 1,477 children. RESULTS: Of the surveyed children 3.5% had at least
      one or more mental or behavioural disorders. The most frequent diagnoses were
      anxiety disorders (1.6%), attention deficit hyperactivity disorder (1.5%) and
      disruptive behaviour disorders (1.5%). Mood disorders (1%) and elimination
      disorders (0.8%) were relatively less common. CONCLUSION: The study shows that
      specific mental and behavioural disorders in these children are significant
      public health problems.

PMID- 12002110
TI  - Anthropometric assessments in Nigerian children.
AB  - OBJECTIVE: To determine the relationship between psychomotor development and the
      anthropometric indices in a sample of Nigerian children. DESIGN: A cross
      sectional study. SETTING: Anthropometric and developmental assessments were
      carried out on the subjects in research rooms or semi-opened spaces that were
      generally conducive for the display of developmental skills by children in the
      various study centres as follows: well baby/ immunisation clinic, nursery schools
      and religious centres. SUBJECTS: Ninety six apparently healthy children aged 7.5,
      10, 12, 18, 24 and 30 months (sixteen subjects in each age group) were assessed
      in the various study centres. MAIN OUTCOME MEASURES: The anthropometric indices
      of weight, height and mid upper arm circumference (MUAC) were measured on each
      subject; who was in turn subsequently assessed with the Bayley Scales of Infant
      Development (BSID): a performance developmental inventory. RESULTS: The
      anthropometric indices of the subjects were found to steadily rise with age but
      below normal standard values for each corresponding age group. However, all the
      subjects scored above the normal minimal developmental index of 50 when assessed
      with the BSID. CONCLUSION: The finding in this study is in line with the
      submission of earlier authors that malnutrition (as indicated by the
      anthropometric indices) on its own alone may not necessarily cause poor
      psychomotor development but perhaps in synergy with some other environmental
      factors linked with retarded development. Based on the anthropometric findings in
      this study, it is suggested by the authors that concerted efforts should be made
      to improve the nutritional states of the Nigerian children so as to, among other
      things, enhance their maximal developmental potential.

PMID- 12002111
TI  - Renal transplantation during the twentieth century: a review.
AB  - OBJECTIVES: To provide an overview of the various advancements and problems
      associated with both live and cadaver donor renal allograft transplantation
      during the twentieth century. DATA SOURCE: Major published reviews on renal
      transplantation during the the last five decades of the twentieth century were
      reviewed using Medline internet search and the Index Medicus. The developments in
      immunosuppressive therapy associated with renal transplantation, the problem of
      the shortage of both live and cadaveric organ donors and post-transplant
      complications were examined. The future of renal transplantation including cross
      species transplantation (xenotransplantation) is discussed. CONCLUSION: Renal
      transplantation has evolved over the years to become a very successful and
      routine procedure. However, the transplant waiting lists have remained long due
      to a continuously shrinking kidney donor pool which is due to improved results of
      neurosurgical procedures, better emergency and intensive care services and the
      failure to adequately prevent and treat post transplant chronic renal failure.

PMID- 12002112
TI  - Cerebellar parameters in developing 15 day old rat pups treated with
      propylthiouracil in comparison with 5 and 24 day old.
AB  - OBJECTIVE: To investigate and quantify structural parameters in the developing
      cerebellum during hypothyroidism in pre and postnatal stages in 15 day old rat
      pups in comparison with 5 and 24 day old. METHODS: Propylthiouracil (PTU) was fed
      to rat dams during mating, pregnancy and nursing and their pups in drinking
      water. Consequently hypothyroxinemia was induced in the dams and the developing
      foeti during prenatal period and maintained in the dams and pups. The number of
      treated and control dams was five in each group. The treated and control pups
      were eight and eleven respectively. The whole cerebellum was dissected out and
      routinely processed for histological and morphometric analysis. Structural
      changes in cerebellum were estimated using "design based" stereological methods.
      The total volume of cerebellum, intracerebellar nuclei and cerebellar
      compartments were estimated using Cavalieri Principle. Numerical density of cells
      was estimated using the disector method and the total cell number was then
      calculated. RESULTS: In the 15 day pups there was significant reduction (P<0.05)
      in the mean volumes of cerebellum, internal granular layer, molecular layer,
      cerebellar cortex, mean ratio of the total volume of intracerebellar nuclei to
      the cerebellar volume and increased mean volume of external granular layer in
      treated pup group compared with control. The mean volumes of intracerebellar
      nuclei and white matter and the mean numerical densities and total numbers of
      neurons and Purkinje cells in intracerebellar nuclei and cerebellum respectively
      were nearly equal in control and treated groups. Significant increase (P<0.05) in
      the mean numerical density and total number of glial cells in treated pups
      compared with control was observed. There was significant decrease (P<0.05) in
      the mean neuron/neuroglia ratio in the intracerebellar nuclei, mean numerical
      density and mean total number of granule cells and reduction in the mean ratio of
      total number of granule/Purkinje cells in the treated group compared with
      control. The linear regression comparison for the total volume of the
      intracerebellar nuclei to total volume of the cerebellum in 5, 15 and 24 day
      control and treated pups and for the total number of glial cells on the total
      volume of intracerebellar nuclei in the same were significantly different
      (P<0.05). Total numbers of neurons and glial cells in the intracerebellar nuclei
      showed peak values in 15 day pups. CONCLUSION: Thus PTU-induced hypothyroidism
      causes variation in quantitative structural parameters in developing cerebellum
      and disrupts progressive cellular developmental processes. Maintenance of normal
      T4 and T3 levels during growth and maturation of cerebellum is absolutely
      essential.

PMID- 12002113
TI  - Tubularised, incised plate urethroplasty for distal hypospadias.
AB  - BACKGROUND: Overtheyears our results of urethroplasty for hypospadias were
      dissatisfactory. We have used different surgical methods for repair of
      hypospadias and we had had about 76% fistula formation, urethroplasty break-down.
      For this reason, we are looking for surgical procedures which can improve our
      results such as less complications and good cosmetic appearance of the glans. The
      tubularised, incised plate urethroplasty for distal hypospadias described in the
      literature is a very attractive procedure with few reported complications and
      good cosmetic results. OBJECTIVE: To describe the distal urethroplasty and
      glanuloplasty procedure, a modification of the Thiersh-Dupley method to determine
      indications, outcome and complications. DESIGN: Prospective clinical study.
      SETTING: Paediatric Surgical Unit, Kenyatta National Hospital, Nairobi, Kenya.
      SUBJECTS: Twenty patients aged one and a half to seven years with coronal,
      subcoronal and midshaft penile hypospadias variant underwent Thiersh-Duplay
      procedure with Snodgrass modification. RESULTS: Meatal stenosis occurred in two
      boys. In one patient, meatal stenosis responded to one dilatation. In the second
      patient a meatotomy was performed. Fistulae developed in four patients. In one
      patient the fistula closed spontaneously after one month on its own. CONCLUSION:
      The advantages of distal hypospadias repair using a tubularised, incised urethral
      plate are: it gives an excellent cosmetic and functional result and a decreased
      risk of urethroplasty breakdown, fistula formation and meatal stenosis.

PMID- 12002114
TI  - Trachea stabilisation with autologous costal cartilage in acquired
      tracheomalacia: report of two cases.
AB  - Post-operative tracheomalacia is a life threatening condition whose management is
      challenging. Surgical procedures which have been suggested in the literature to
      manage the condition include tracheostomy, staged thyroid reductions and the use
      of artificial stents either within the lumen of the tracheobronchial tree or as
      external support. We report the successful management of two patients using
      autologous costal cartilage to support the tracheal wall.

PMID- 12002115
TI  - Plummer Vinson syndrome: case report.
AB  - Plummer Vinson syndrome is characterised by dysphagia, iron deficiency, anaemia
      and oesophageal web or webs. This is a case report of a 33 year old Asian female
      who presented with slowly progressive dysphagia and a long history of iron
      deficiency anaemia. The anaemia was confirmed on repeated haemograms and a barium
      swallow revealed an upper oesophageal web. Upper gastrointestinal endoscopy and
      forceful dilatation were necessary to effect relief of dysphagia.

PMID- 12002116
TI  - Hodgkin's disease after treatment for Burkitt's lymphoma: case report.
AB  - Hodgkin's disease and non-Hodgkin's lymphomas are interrelated disorders which
      have been reported to occur either simultaneously or sequentially in the same
      patient. We report here the development of nodular sclerosing type Hodgkin's
      disease in a patient two decades after successful treatment for Burkitt's
      lymphoma with cyclophosphomide and abdominal resection (AR). While the onset of
      symptoms after treatment for Burkitt's lymphoma was seven years definitive
      diagnosis of Hodgkin's disease was only made 22 years after the initial diagnosis
      of Burkitt's lymphoma. The recurrent and solitary nature ofthe lymphadenopathy
      and the fact that it was initially reported as reactive hyperplasia is typical of
      nodular lymphocyte predominant Hodgkin's disease. We believe that there was a
      transitory period of the malignancy as nodular lymphocyte predominant Hodgkin's
      disease.

PMID- 12002117
TI  - Tuberculosis in Ibadan, Nigeria--a 30 year review.
AB  - OBJECTIVES: Recent reports have indicated a re-emergence of tuberculosis (TB)
      worldwide, particularly in the USA, where this re-emergence has been attributed
      mainly to immunosuppression by HIV. Information on the pattern and trend of TB is
      scarce in the developing countries, including Nigeria. This present study was set
      out to review the pattern of TB in the University College Hospital (UCH), Ibadan,
      between 1966 to 1995 with emphasis on changing trend between two time periods:
      1966 to 1980 and 1981 to 1995. DESIGN: A 30 year retrospective review of all
      cases of tuberculosis diagnosed from surgical pathology and autopsy in the
      Department of Pathology, UCH, Ibadan, between January 1966 and December 1995 was
      done. The age, sex, details of organ involvement and biopsy site of the cases
      were studied and the data obtained was tabulated and analysed statistically.
      RESULTS: Tuberculosis in this environment affects predominantly individuals below
      40 years of age with peak age frequency between 21 to 30 year age range. More
      females are affected with TB with twice as many females as males being affected
      in the reproductive years. There were significant declines in tuberculous
      involvement of the female genital tract, bone and skin in the second period 1981
      to 1995 compared to the first period 1966 to 1980. The frequency of miliary TB
      remained high in the second period. Deaths from tuberculosis were highest in the
      age group zero to 10 years, with deaths in all age groups being due to
      disseminated TB and TB meningitis. CONCLUSION: Socio-economic factors and poor
      health care facilities rather than HIV appear to be more important contributing
      factors to the gradual increase in the frequency of tuberculosis in the second
      period of this study.

PMID- 12002118
TI  - The incidence of cleft lip, cleft palate, hydrocephalus and spina bifida at Queen
      Elizabeth Central Hospital, Blantyre, Malawi.
AB  - OBJECTIVES: To determine the incidence of cleft lip, cleft palate, spina bifida
      and hydrocephalus; and to compare these with those of Asian and European
      subjects. DESIGN: A retrospective study. SETTING: The Queen Elizabeth Central
      Hospital (QECH) in Blantyre, Malawi. SUBJECTS: Delivery and nursery records
      compiled between January 1998 and December 1999 were studied. MAIN OUTCOME
      MEASURES: To measure the incidence of cleft lip, cleft palate, spina bifida and
      hydrocephalus. RESULTS: Of the total 25562 births, 39 (0.2%) had defects; eight
      boys and 31 girls. Clefts (all types) comprised the largest group, 43.6%, with an
      incidence of 0.67/1 000; spina bifida, 30.8% with an incidence of 0.47/1000;
      hydrocephalus, 15.4%, and an incidence of 0.23/1000; and spina bifida with
      hydrocephalus, 10.3%, with 0.16/1000 incidence. The respective mean (SD) birth
      weights for clefts (all types), spina bifida, hydrocephalus and spina bifida with
      hydrocephalus were 2806.47 (569.07) g, 2650.00 (360.55) g 2610.00 (720.97) g and
      3362.50 (696.87) g respectively. CONCLUSION: Our findings show a higher incidence
      of spina bifida in Malawians than in Caucasians and Orientals, but the incidence
      was lower than Omani subjects. The incidence of clefts and hydrocephalus in black
      Malawians, however, was lower than previously reported in other population
      groups, and hydrocephalus probably showed the lowest incidence among blacks in
      the continent. Furthermore, congenital malformations affected more girls than
      boys 4:1, but the infants had normal birth weight.

PMID- 12002119
TI  - Antibiotic sensitivity and plasmid profiles of Pseudomonas aeruginosa.
AB  - OBJECTIVE: To determine the susceptibility of Pseudomonas aeruginosa to commonly
      used antibiotics and to study the relationship between antibiotic resistance and
      the plasmid profiles of the organism. DESIGN: Cross sectional study SETTING:
      Samples of burns, wound pus, urine, blood, sputum, stool and aspirates were
      obtained from Harare Hospital (n = 120) and Parirenyatwa Hospital(n = 80).
      SUBJECTS: Male and female patients either admitted or attending clinics. MAIN
      OUTCOME MEASURES: P. aeruginosa isolates obtained were resistant to commonly used
      antibiotics in this environment. The resistance may be plasmid-dependent.
      RESULTS: P. aeruginosa is prevalent in burns (76.7%) and wounds (67.5%) and in
      their respective hospital wards. The isolates of P. aeruginosa were resistant to
      gentamicin (65.5%); carbenicillin (61.9); polymyxinb (53.0%); ciprofloxacin
      (61.1%) and ceftriazone (70.8%); but showed high sensitivity to tazocin (89.4%)
      and nalidixic acid (59.3%) and cotrimoxazole (54.9%). All the isolates resistant
      to the antibiotics tested possessed plasmid DNA. Strains with four plasmids of
      molecular weight of approximately, 1.5 x 10(6), 1.8 x 10(6), 2.9 x 10(6) and 7.4
      x 10(6) Da showed multiple resistance to the drugs that were tested. CONCLUSION:
      This study reveals an emergence of multiple antibiotic-resistant strains of P.
      aeruginosa. The traditional drugs gentamicin, carbenicillin, ciproflaxacin, and
      polymyxin-b used for treatment of P. aeruginosa infections may no longer be
      reliable. Therefore, a newer drug such as tazocin and other rarely used drugs
      such as nalidixic acid should be considered for P. aeruginosa antibiotic therapy.

PMID- 12002120
TI  - Indications for corneal grafting in Zimbabwe.
AB  - OBJECTIVE: To assess the indications for corneal grafting in Zimbabwe. DESIGN:
      Hospital based retrospective study. SETTING: The study was conducted at Sekuru
      Kaguvi Eye Hospital. METHODS: Data were collected for patients who had corneal
      grafts performed at Sekuru Kaguvi Eye Hospital during the period January 1992 to
      March 1998. RESULTS: The leading indications for penetrating keratoplasty were
      keratoconus (26.8%), presumed post measles scarring (17.8%), pseudophakic bullous
      keratopathy (12.5%), corneal scarring due to Herpes simplex keratitis (10.7%) and
      corneal scarring due to trauma (10.7%). A change in the indications was observed
      during the study period. The outcome of corneal grafting was favourable with more
      than 75% experiencing significant improvement in vision. CONCLUSION: Indications
      for penetrating keratoplasty in Zimbabwe show a pattern different from those for
      the developed world. A change in the indications during the study reflects
      changes in local ophthalmic practice.

PMID- 12002121
TI  - Factors affecting condom use among senior secondary school pupils in South
      Africa.
AB  - OBJECTIVES: The aim of the study was to investigate factors affecting condom use
      among senior secondary school pupils in South Africa. Objectives were to identify
      the sociodemographic characteristics and sexual history, knowledge about correct
      condom use, source of condom information, AIDS health beliefs, self efficacy of
      condom use, correlates and predictors of condom use in Grade 12 students. DESIGN:
      Cross sectional survey. SETTING: 460 Grade 12 secondary school pupils from three
      rural schools. SUBJECTS: The sample included 460 Grade 12 secondary school
      pupils, 170 (37%) males and 290 (63%) females in the age range of 16 to 30 years
      (mean age 19.7 yrs, SD = 2.5). MAIN OUTCOME MEASURES: Self reported sexual
      activity and condom use (12 items); source of 'condom' information (12 items);
      knowledge of correct condom use (10 items); a 16 item AIDS Health Belief Scale
      and a 28 item Condom Use Self-Efficacy Scale. RESULTS: About half of those
      sexually active (52.6% males and 40.5% females) reported never having used
      condoms. About 90% levels of correct answers on condom knowledge were found for
      the items of "protection against AIDS" and "expire date of condoms". Knowing
      someone with HIV/AIDS was related to current condom use and a history of STD with
      lifetime condom use. The four AIDS beliefs sub-scales were all related to self
      efficacy of condom use. Behavioural norm to use condoms, attitudes towards condom
      use, normative beliefs to use of condoms and subjective norm to use condoms were
      all related to condom use intention. Normative beliefs and subjective norms to
      use condoms were both negatively related with lifetime condom use, current condom
      use, and self efficacy in condom use. Normative beliefs, attitudes and subjective
      norms about condoms predicted condom use intention, AIDS susceptibility and AIDS
      benefits predicted condom use with last sexual partner, and AIDS benefits and
      AIDS barriers predicted condom use intention. CONCLUSION: Findings have relevant
      implications and are discussed in the context of developing an educational or
      intervention programme.

PMID- 12002122
TI  - The management of cervical intra-epithelial neoplasia.
AB  - The aim of this article is to discuss the management of a woman with cervical
      intra-epithelial neoplasia based on current scientific knowledge of disease
      progression from cervical pre-cancer to invasive squamous cancer. Interpretation
      of cytology (Papanicolou Smear) results and the currently advocated treatment
      modalities are also discussed.

PMID- 12002123
TI  - A new device for measuring the viscoelastic properties of hydrated matrix gels.
AB  - Determinations of the viscoelastic properties of extracellular matrices (ECMs)
      are becoming increasingly important for accurate predictive modeling of
      biological systems. Since the interactions of the cells with the ECM and
      surrounding fluid (e.g., blood, media) each affect cell behavior; it is
      advantageous to evaluate the ECM's material properties in the presence of the
      hydrating fluid. Conventional rheometry methods evaluate the bulk material
      properties of gel materials while displacing the hydrating liquid film. Such
      systems are therefore nonideal for testing materials such as ECMs, whose
      properties change with dehydration. The new patent pending, piezoelectrically
      actuated linear rheometer is designed to eliminate this problem. It uses a single
      cantilever to apply an oscillating load to the gel and to sense the gel's
      deflection. Composed of two thin film piezopolymer layers, the cantilever uses
      one layer as the actuator, and the second piezopolymer layer to measure the
      lateral movement of its attached probe. The viscoelastic nature of the ECM adds
      stiffness and damping to the system, resulting in the attenuation and phase shift
      of the sensor's output voltage. From these parameters, the ECM's shear storage
      and loss moduli are then determined. Initial tests on the BioMatrix I and type I
      collagen ECMs reveal that the first prototype of the piezoelectrically actuated
      linear rheometer is capable of accurately determining the trend and order of
      magnitude of an ECM's viscoelastic properties. In this paper, details of the
      rheometer's design and operating principles are described.

PMID- 12002124
TI  - An analysis of turbulent shear stresses in leakage flow through a bileaflet
      mechanical prostheses.
AB  - In this work, estimates of turbulence were made from pulsatile flow laser Doppler
      velocimetry measurements using traditional phase averaging and averaging after
      the removal of cyclic variation. These estimates were compared with estimates
      obtained from steady leakage flow LDV measurements and an analytical method. The
      results of these studies indicate that leakage jets which are free and planar in
      shape may be more unstable than other leakage jets, and that cyclic variation
      does not cause a gross overestimation of the Reynolds stresses at large distances
      from the leakage jet orifice.

PMID- 12002125
TI  - On assessing the quality of particle tracking through computational fluid dynamic
      models.
AB  - Quantification of particle deposition patterns, transit times, and shear exposure
      is important for computational fluid dynamic (CFD) studies involving respiratory
      and arterial models. To numerically compute such path-dependent quantities, it is
      necessary to employ a Lagrangian approach where particles are tracked through a
      pre-computed velocity field. However, it is difficult to determine in advance
      whether a particular velocity field is sufficiently resolved for the purposes of
      tracking particles accurately. Towards this end, we propose the use of volumetric
      residence time (VRT)--previously defined for 2-D studies of platelet activation
      and here extended to more physiologically relevant 3-D models--as a means of
      quantifying whether a volume of Lagrangian fluid elements (LFE's) seeded
      uniformly and contiguously at the model inlet remains uniform throughout the flow
      domain. Such "Lagrangian mass conservation" is shown to be satisfied when VRT=1
      throughout the model domain. To demonstrate this novel concept, we computed maps
      of VRT and particle deposition in 3-D steady flow models of a stenosed carotid
      bifurcation constructed with one adaptively refined and three nominally uniform
      finite element meshes of increasing element density. A key finding was that
      uniform VRT could not be achieved for even the most resolved meshes and densest
      LFE seeding, suggesting that care should be taken when extracting quantitative
      information about path-dependent quantities. The VRT maps were found to be useful
      for identifying regions of a mesh that were under-resolved for such Lagrangian
      studies, and for guiding the construction of more adequately resolved meshes.

PMID- 12002126
TI  - Microscopic velocimetry with a scaled-up model for evaluating a flow field over
      cultured endothelial cells.
AB  - A microscopic velocimetry technique for evaluating the flow field over cultured
      endothelial cells was developed. Flow around a cell model scaled up by a factor
      of 100 was visualized by using an optical microscope and was quantified by using
      particle-tracking velocimetry. Wall shear stress on the model surface was
      determined from a two-dimensional velocity field interpolated from measured
      velocity vectors. Accuracy of the velocimetry was verified by measuring the flow
      over a sinusoidal cell model that had a wall shear stress profile analytically
      determined with linear perturbation theory. Comparison of the experimental
      results with the analytical solution revealed that the total error of the
      measured wall shear stress was 6 percent.

PMID- 12002127
TI  - Nanostructure, effective properties, and deformation pattern of the cochlear
      outer hair cell cytoskeleton.
AB  - We consider the mechanical properties of the outer hair cell cytoskeleton. The
      cytoskeleton is represented as a set of microdomains of different sizes and
      orientations composed of actin filaments and spectrin crosslinks. An intermediate
      material between domains is also introduced. The domain characteristics are
      randomly generated and the histograms of the cytoskeleton stiffness moduli are
      obtained. We solve an inverse problem and estimate the stiffness of the crosslink
      and connective molecule in the intermediate material. We discovered a pattern of
      highly inhomogeneous deformation of the cytoskeleton where the circumferential
      strain is primarily determined by the deformation of the intermediate material.

PMID- 12002128
TI  - The Differential Interfacial Tension Hypothesis (DITH): a comprehensive theory
      for the self-rearrangement of embryonic cells and tissues.
AB  - A comprehensive theory, herein named the Differential Interfacial Tension
      Hypothesis for the self-rearrangement of embryonic cells and tissues is
      presented. These rearrangements include sorting, mixing and formation of
      checkerboard patterns in heterotypic aggregates of embryonic cells, and total or
      partial engulfment, separation and dissociation of tissues. This broadly-based
      theory accounts for the action of all currently known cytoskeletal components and
      cell adhesion mechanisms. The theory is used to derive conditions for the cell
      and tissue rearrangements named above. Finite element-based computer simulations
      involving two or more cell types confirm these conditions.

PMID- 12002129
TI  - Predicting local cell deformations in engineered tissue constructs: a multilevel
      finite element approach.
AB  - A multilevel finite element approach is applied to predict local cell
      deformations in engineered tissue constructs. Cell deformations are predicted
      from detailed nonlinear FE analysis of the microstructure, consisting of an
      arrangement of cells embedded in matrix material. Effective macroscopic tissue
      behavior is derived by a computational homogenization procedure. To illustrate
      this approach, we simulated the compression of a skeletal muscle tissue construct
      and studied the influence of microstructural heterogeneity on local cell
      deformations. Results show that heterogeneity has a profound impact on local cell
      deformations, which highly exceed macroscopic deformations. Moreover,
      microstructural heterogeneity and the presence of neighboring cells leads to
      complex cell shapes and causes non-uniform deformations within a cell.

PMID- 12002130
TI  - A novel in-vitro system for the simultaneous exposure of bladder smooth muscle
      cells to mechanical strain and sustained hydrostatic pressure.
AB  - The novel hydrostrain system was designed in an effort to establish and maintain
      conditions that simulate the in-vivo mechanical environment of the bladder. In
      this laboratory system, ovine bladder smooth muscle cells on flexible, 10-cm-dia
      silastic membranes were exposed simultaneously to hydrostatic pressure (40 cm
      H2O, a pressure level currently associated with bladder pathologies) and
      mechanical strains (up to 25 percent) under standard cell culture conditions for
      7 h. Under these conditions, Heparin Binding-Epidermal Growth Factor and Collagen
      Type III mRNA expression were significantly increased (p<0.01 and 0.1,
      respectively); however, no changes were observed in Collagen Type I mRNA
      expression. Decreases in the Collagen Type I:Type III ratio following
      simultaneous exposure of bladder smooth muscle cells to pathological levels of
      hydrostatic pressure and mechanical strain in vitro are in agreement with
      clinically observed increases in Collagen Type III with concomitant decreased
      human bladder compliance. The results of the present study, therefore, provide
      cellular/molecular level information relevant to bladder pathology that could
      have significant implications in the field of clinical urology.

PMID- 12002131
TI  - Tensile mechanical properties of three-dimensional type I collagen extracellular
      matrices with varied microstructure.
AB  - The importance and priority of specific micro-structural and mechanical design
      parameters must be established to effectively engineer scaffolds (biomaterials)
      that mimic the extracellular matrix (ECM) environment of cells and have clinical
      applications as tissue substitutes. In this study, three-dimensional (3-D)
      matrices were prepared from type I collagen, the predominant compositional and
      structural component of connective tissue ECMs, and structural-mechanical
      relationships were studied. Polymerization conditions, including collagen
      concentration (0.3-3 mg/mL) and pH (6-9), were varied to obtain matrices of
      collagen fibrils with different microstructures. Confocal reflection microscopy
      was used to assess specific micro-structural features (e.g., diameter and length)
      and organization of component fibrils in 3-D. Microstructural analyses revealed
      that changes in collagen concentration affected fibril density while maintaining
      a relatively constant fibril diameter. On the other hand, both fibril length and
      diameter were affected by the pH of the polymerization reaction. Mechanically,
      all matrices exhibited a similar stress-strain curve with identifiable "toe,"
      "linear," and "failure" regions. However the linear modulus and failure stress
      increased with collagen concentration and were correlated with an increase in
      fibril density. Additionally, both the linear modulus and failure stress showed
      an increase with pH, which was related to an increasedfibril length and a
      decreasedfibril diameter. The tensile mechanical properties of the collagen
      matrices also showed strain rate dependence. Such fundamental information
      regarding the 3-D microstructural-mechanical properties of the ECM and its
      component molecules are important to our overall understanding of cell-ECM
      interactions (e.g., mechanotransduction) and the development of novel strategies
      for tissue repair and replacement.

PMID- 12002132
TI  - Direct measurement of the Poisson's ratio of human patella cartilage in tension.
AB  - Articular cartilage has been shown to exhibit large transverse contractions when
      loaded in tension, suggesting the existence of large values for the Poisson's
      ratio. Previous studies have suggested that this effect is dependent on amplitude
      of applied strain, so that a single Poisson's ratio may not be sufficient to
      describe cartilage behavior. In this study, the Poisson's ratio (v), toe region
      modulus (Eo), and linear region modulus (E) of human patellar articular cartilage
      were calculated in simple tension tests from optical analysis of the two
      dimensional strain fields at equilibrium. The Poisson's ratio was found to be
      independent of strain due to the absence of viscoelastic effects during testing.
      The Poisson's ratio was found to be significantly higher in the surface zone
      (1.87 +/- 1.11, p<0.01) than in the middle zone (0.62 +/- 0.23), with no
      significant correlation of v with age of the cartilage. In general, values for
      Poisson's ratio were greater than 0.5, suggesting cartilage behavior in tension
      deviates from isotropy. Reported values for the Poisson's ratio of cartilage in
      compression have been much lower than values measured here in tension, reflecting
      a mechanical contribution of the collagen fibers to anisotropy in tension but not
      compression. The toe-region modulus (Eo) was significantly higher in the surface
      zone (4.51 +/- 2.78 MPa, n=8) compared to the middle zone (2.51 +/- 1.93 MPa,
      n=10). In addition, the linear-region modulus (E) in the surface zone, but not
      middle zone (3.42 +/- 2.17 MPa, n=10), was found to correlate with age (R=0.97,
      p<0.02) with values of surface zone E equal to 23.92 +/- 12.29 MPa (n=5) for
      subjects under 70 yr of age, and 4.27 +/- 2.89 MPa (n=3) for subjects over 70 yr.
      Moduli values and trends with depth were consistent with previous studies of
      human and animal cartilage. From direct measures of two independent material
      properties, v and E, we calculated a shear modulus, G, which had not been
      previously reported for cartilage from tensile testing. Calculated values for
      surface zone G were 3.64 +/- 1.80 MPa for subjects under 70 yr old and 0.96 +/-
      0.69 MPa for subjects over 70 yr old, and were significantly higher in the
      surface zone than in the middle zone (1.10 +/- 0.78 MPa). This study provides an
      intrinsic measure for the Poisson's ratio of articular cartilage and its
      dependence on depth which will be important in understanding the nonlinear
      tension-compression and anisotropic behaviors of articular cartilage.

PMID- 12002133
TI  - Effect of annular incision type on the change in biomechanical properties in a
      herniated lumbar intervertebral disc.
AB  - The technique used to incise the disc during discectomy may play a role in the
      subsequent healing and change in biomechanical stiffness of the disc. Several
      techniques of lumbar disc annulotomy have been described in clinical reports. The
      purpose of this paper was to study the influence of annulotomy technique on
      motion segment stiffness using a finite element model. Four incision methods
      (square, circular, cross, and slit) were compared. The analyses showed that each
      of the annular incisions produced increase in motions under axial moment loadings
      with circular incision producing the largest change in the corresponding
      rotational motion. Under shear loading mode, cross and slit-type annular
      incisions produced slightly larger changes in the principal motions of the disc
      than square and circular incisions. All other incision types considered in the
      current study produced negligibly small increase in motion under rest of the
      loading conditions. In addition to annulotomy, when nucleotomy was also included
      in the analyses, once again cross and slit incisions produced larger change in
      motion under shear loading mode as compared to the other two incision types. A
      comparison between the four types of annular incisions showed that cross incision
      produced an increase in motion larger than those produced by the other three
      incisions under flexion/extension and lateral moment loading and both shear force
      loadings. Circular incision produced the largest increase in motion under axial
      moment load in comparison to those produced by square, cross, and slit incisions.
      Sagittal plane symmetry was influenced by the incision injury to the motion
      segment leading to coupled motions as well as increased facet loads. From the
      study it can be concluded that the increase inflexibility of the disc due to
      annulotomy depends on the type of annulotomy and the annulotomy also produce
      asymmetrical deformations leading to increased facet loading.

PMID- 12002134
TI  - Multiphase mechanics of capsule formation in tumors.
AB  - The presence of a capsule around a tumor is known to be correlated with benign
      status, and the absence of a capsule often has negative implications for patient
      prognosis. A mechanical description is presented of the growth of a tumor and the
      resulting deformations of surrounding normal tissue. A mathematical model of the
      mechanics is analyzed using physical parameters measured in vivo and in vitro.
      The model has only three dimensionless parameters, and its results are very
      robust with respect to parameter variation. We show that the presence of
      contractility in the surrounding tissue, corresponding to a host defense, can
      make an existing capsule denser and constrain the tumor better, but cannot be
      responsible for the observed pressure gradients in encapsulated tumors. Some
      implications for treatment are discussed.

PMID- 12002135
TI  - Regional, directional, and age-dependent properties of the brain undergoing large
      deformation.
AB  - The large strain mechanical properties of adult porcine gray and white matter
      brain tissues were measured in shear and confirmed in compression. Consistent
      with local neuroarchitecture, gray matter showed the least amount of anisotropy,
      and corpus callosum exhibited the greatest degree of anisotropy. Mean regional
      properties were significantly distinct, demonstrating that brain tissue is
      inhomogeneous. Fresh adult human brain tissue properties were slightly stiffer
      than adult porcine properties but considerably less stiff than the human autopsy
      data in the literature. Mixed porcine gray/white matter samples were obtained
      from animals at "infant" and "toddler" stages of neurological development, and
      shear properties compared to those in the adult. Only the infant properties were
      significantly different (stiffer) from the adult.

PMID- 12002136
TI  - A noncontact, nondestructive method for quantifying intratissue deformations and
      strains.
AB  - The function of soft connective tissues is frequently characterized by
      quantifying tissue strain (e.g., during joint motion). Conventional techniques
      for quantifying tendon and ligament strain typically provide surface measures,
      using markers, stain lines or instrumentation that may influence the tissue. An
      alternative approach is to quantify intratendinous strain by applying texture
      correlation analysis to magnetic resonance (MR) images. This paper reports the
      accuracy and reproducibility of this approach by (1) assessing the
      reproducibility of MR images, (2) assessing texture correlation accuracy using
      simulated displacements, and (3) comparing texture correlation measures of
      displacement and strain from MR images to conventional techniques.

PMID- 12002137
TI  - A new flow chamber for the study of shear stress and transmural pressure upon
      cells adhering to a porous biomaterial.
AB  - Biomaterials used in some biomedical devices are porous and exposed to normal and
      tangential flow of biofluids. To examine the influence of flow induced forces on
      the morphology and the biochemical responses of cells adhering to such
      biomaterials, a Hele-Shaw cell with a porous bottom wall was designed and
      characterized experimentally. Theoretical predictions for the flow in the chamber
      are provided and allow to quantify the shear stress and/or transmural pressure
      exerted on cells. It is thus possible to follow up continuously the shape changes
      of cells that are adherent on a permeable membrane used in bioreactors.

PMID- 12002138
TI  - Syndromic dystelephalangy.
AB  - We report an 8-year-old boy with a distinctive facial phenotype, deformities of
      fingers and toes and limitation of knee movement of unknown etiology. He had a
      round face, a long nose, a thin upper lip, a small mouth and micrognathia. In
      spite of microcephaly and retarded speech development secondary to hearing loss
      his mental development was within normal limits. The most distinctive
      radiographic abnormality was hypoplasia of the distal end of the middle phalanges
      with radial deviation of the distal phalanges.

PMID- 12002139
TI  - Male siblings with dyserythropoiesis, microcephaly and intrauterine growth
      retardation.
AB  - Male siblings with intrauterine growth retardation, hydrops, mild liver
      dysfunction, chronic diarrhoea, failure to thrive and microcephaly are reported.
      In both patients, the intrauterine growth retardation was detected in the second
      trimester of pregnancy. Relatively severe early onset neonatal jaundice,
      microcytosis, anisocytosis and abnormal iron metabolism were also seen. Bone
      marrow examination in the second sibling showed marked ringed sideroblasts and
      multilobulated erythroblasts in late developmental stages. The brain was very
      small with enlarged cerebrospinal fluid space, a reduced number of gyri and a
      thin cortex. The clinical and laboratory findings in these patients appear to be
      unique.

PMID- 12002140
TI  - Microdeletion 22q11.2, Kousseff syndrome and spina bifida.
AB  - A fetus was diagnosed on ultrasound scan as having sacral spina bifida and a
      ventricular septal defect in the heart. At postmortem examination the cardiac
      defect was found to be a conotruncal abnormality, and there was a cleft palate,
      some facial dysmorphism as well as the spina bifida. A diagnosis of Kousseff
      syndrome was made, but detailed cytogenetics subsequently revealed a 22q11.2
      deletion. In the light of these findings, and on review of the literature, we
      suggest that spina bifida is recognized as a feature of the variable phenotype
      associated with this microdeletion.

PMID- 12002141
TI  - Facial appearance in glycogen storage disease type III.
AB  - Amylo-1,6-glucosidase deficiency (glycogen storage disease type III) is
      associated with hypoglycaemia, hepatomegaly, raised transaminases and in most
      cases skeletal myopathy and cardiomyopathy. The disorder has not been considered
      to cause dysmorphism. We report consistent facial features in seven patients with
      GSD type III consisting of midface hypoplasia with a depressed nasal bridge and a
      broad upturned nasal tip, indistinct philtral pillars, and bow-shaped lips with a
      thin vermillon border. Younger patients had in addition deepset eyes. Several
      children had clinical problems such as persistent otitis media or recurrent
      sinusitis. The underlying aetiology of these features is unknown but the
      similarity in all our patient suggests that there is a facial phenotype for this
      disorder.

PMID- 12002142
TI  - Sotos syndrome: two cases with severe scoliosis.
AB  - Two patients with Sotos syndrome who developed a severe scoliosis are described.
      These cases illustrate the potential to develop significant spinal curvature in
      Sotos syndrome.

PMID- 12002143
TI  - Cervical diastematomyelia in cervico-oculo-acoustic (Wildervanck) syndrome: MRI
      findings.
AB  - Cervico-oculo-acoustic (COA) or Wildervanck syndrome is characterized by the
      triad of Klippel-Feil anomaly, bilateral abducens palsy with retracted bulbs
      (Duane 'syndrome') and hearing loss. The clinical findings of this syndrome have
      been well documented. A few case reports with MRI findings have appeared in the
      literature showing brainstem and cerebellar hypoplasia and vertebral segmentation
      anomalies. Our case is unique in that diastematomyelia of the lower medulla and
      cervical cord was accompanied by vermian hypoplasia, tonsillar herniation and
      resulting triventricular hydrocephalus in a child with Wildervanck syndrome. This
      case is presented with MR images. Children with Wildervanck syndrome should be
      investigated for craniospinal abnormalities with MR imaging.

PMID- 12002144
TI  - Guadalajara camptodactyly syndrome type I: report on a new case.
AB  - We report a Brazilian female patient with a thin and long face, blepharophimosis,
      minor auricular anomalies, camptodactyly and thoracic and spinal anomalies. The
      constellation of clinical signs present in this patient is consistent with the
      diagnosis of Guadalajara camptodactyly syndrome type I. Clinical and genetic
      aspects concerning this condition are discussed.

PMID- 12002145
TI  - DOOR syndrome: report of three additional cases.
AB  - Three new cases of DOOR syndrome are described in unrelated Brazilian children.
      One of these cases also has a congential cardiac defect. None of the cases has
      organic acid abnormalities and they can therefore be classified as Type II.

PMID- 12002146
TI  - Bilateral anophthalmia and oesophageal atresia in a newborn female: a new case of
      the anophthalmia-oesophageal-genital (AEG) syndrome.
AB  - A newborn female is described with bilateral anophthalmia and oesophageal
      atresia. This is the seventh reported case of the Anophthalmia-Oesophageal
      Genital (AEG) syndrome.

PMID- 12002147
TI  - Unilateral split foot, torticollis, congenital heart defect and hydrocephaly: a
      new syndrome?
AB  - We report a patient showing unilateral split foot together with unusual
      malformations.

PMID- 12002148
TI  - Auriculo-condylar syndrome or new syndrome?
AB  - We describe a girl with peculiar auricular dysmorphism, renal agenesis and
      supernumerary rib. Some different diagnostic hypotheses are discussed.

PMID- 12002149
TI  - 46,XY,der(3)t(1;3)(q23;p22): double aneuploidy at a new breakpoint.
AB  - A 12-month-old Omani boy is described with double aneuploidy involving
      chromosomes 1 and 3. In this case the aberration involved segment (q23;p22) which
      has not been reported previously.

PMID- 12002150
TI  - Bowen-Conradi syndrome in non Hutterite infant.
AB  - The authors' review their experience of Bowen-Conradi syndrome and the available
      literature. They point out that there have been three previously published
      reports of possible Bowen-Conradi syndrome in non Hutterite children.

PMID- 12002151
TI  - Bowen-Conradi syndrome.

PMID- 12002152
TI  - Congenital diaphragmatic hernia in a female patient with craniofrontonasal
      syndrome.
AB  - A 21-month-old Caucasian female with the combination of craniofrontonasal
      syndrome and a posterolateral defect of the diaphragm (type Bochdalek) is
      described. This is thought to be a previously undescribed combination. Pedigree
      analysis is consistent with an X-linked mode of inheritance of the
      craniofrontonasal syndrome.

PMID- 12002153
TI  - An autosomal recessive syndrome of choanal atresia, hypothelia/athelia and
      thyroid gland anomalies overlapping bamforth syndrome, ANOTHER syndrome and
      methimazole embryopathy.
AB  - Two sibs from an inbred Arab family are described with an autosomal syndrome of
      choanal atresia, hypothelia/athelia and thyroid gland anomalies overlapping
      Bamforth syndrome, ANOTHER syndrome and methimazole embryopathy. In one case the
      syndrome described was lethal. Cases with similar features are reviewed and
      genetic mutations discussed.

PMID- 12002154
TI  - Symmetrical upper limb peromelia and lower limb phocomelia associated with a de
      novo apparently balanced reciprocal translocation: 46,XX,t(2; 12)(p25.1;q24.1).
AB  - We report a female fetus of 20 weeks gestation with severe symmetrical deformity
      affecting all four limbs. These deformities were unusual in that there was upper
      limb peromelia and lower limb phocomelia. No additional major malformations were
      identified on postmortem examination. In particular there was no evidence of
      splenogonadal fusion or micrognathia and hypoglossia. The limb malformations in
      this case are associated with a de novo apparently balanced reciprocal
      translocation 46,XX,t(2;12)(p25.1;q24.1). The cytogenetic features of Roberts-SC
      phocomelia syndrome were not detected. Unfortunately, the fibroblast line died
      and no FISH or DNA analysis could be carried out. In spite of this, the case is
      presented as it may be useful to other researchers in the selection of candidate
      genes for mendelian forms of peromelia and phocomelia.

PMID- 12002155
TI  - Further delineation of mandibulofacial dysostosis: Toriello type.
AB  - We report a boy who presented with mild mandibulofacial dysostosis, growth
      retardation with microcephaly, bilateral hearing loss, thoracic deformity with a
      cardiac valvular lesion and bilateral cryptorchidism. The pattern of
      malformations differs from the classical Treacher Collins syndrome. We consider
      it to be mandibulofacial dysostosis (MFD), Toriello type with some additional
      features.

PMID- 12002156
TI  - Kabuki syndrome: a review study of three hundred patients.
AB  - The Kabuki (make-up) syndrome identified in 1981 has been reported in more than
      three hundred patients. Typical findings include mild to moderate mental
      retardation, fetal pads, cleft palate, and characteristic facies with long
      palpebral fissures, everted lower lateral eyelids and arched eyebrows. Postnatal
      growth retardation, skeletal and visceral anomalies are present in a large
      percentage of patients. We review here the characteristics of this peculiar
      syndrome in three hundred patients.

PMID- 12002157
TI  - External time--internal time.

PMID- 12002158
TI  - Tales from the crypt(ochromes).
AB  - Cryptochromes are a family of flavoproteins found in organisms ranging from
      Arabidopsis to man. Across phylogeny, these proteins have been used for
      pleiotropic functions ranging from blue-light-dependent development in plants and
      blue-light-mediated phase shifting of the circadian clock in insects to a core
      circadian clock component in mammals. Review of the roles of cryptochromes in
      model organisms reveals several common themes: Multiple cryptochrome family
      members within individual organisms have redundant functions; cryptochromes used
      in photic entrainment pathways of the circadian clock are partially redundant
      with other photopigments; and cryptochromes may function in circadian
      phototransduction and core clock mechanisms in the same organism, with different
      functions in different tissues. The present review summarizes recent research on
      the functions of cryptochrome in the circadian timekeeping and photic entrainment
      pathways.

PMID- 12002159
TI  - Analysis of immunohistochemical label of Fos protein in the suprachiasmatic
      nucleus: comparison of different methods of quantification.
AB  - The induction of the proto-oncogene c-fos, and its phosphoprotein product Fos,
      has been extensively used to study the effects of light on the circadian
      pacemaker in the suprachiasmatic nucleus (SCN). Experimental approaches to the
      quantification of Fos induction have mainly been based on immunohistochemistry
      and subsequent measure of Fos immunoreactivity (IR) in sections of the SCN. In
      this study, the authors compare several methods of quantification using optical
      density image analysis or counts of Fos-IR labeled cells. To assess whether
      optical density measures using image analysis reflect the amount of Fos in brain
      tissue, the authors developed standards of known concentrations of Fos protein in
      an agar matrix. The agar standards were sectioned and treated simultaneously with
      sections of the SCN from animals exposed to different levels of irradiance.
      Optical density was found to be proportional to the quantity of Fos in the
      sections, indicating that this measure accurately reflects relative levels of Fos
      protein induction. Quantification by optical density analysis allows an objective
      measure in which the various parameters, conditions of illumination, and
      threshold can be maintained constant throughout the analysis. Counting cells by
      visual observation is more subjective because threshold values cannot be
      precisely defined and can vary according to the observer, illumination, degree of
      label, and other factors. In addition, cell counts involving direct visual
      observation, automated cell counts, or stereological methods do not take into
      account the difference in the density of label between cells, thus giving equal
      weight to lightly or densely stained cells. These measures are more or less
      weakly correlated with measures of optical density and thus do not accurately
      reflect the amount of bound Fos protein in the tissue sections. In contrast,
      labeled surface area as measured by image analysis shows a linear relationship
      with optical density. The main outcome of this study is that computer-assisted
      image analysis provides an accurate and rapid method to determine the relative
      amount of Fos protein in the SCN and the effects of light on intracellular
      signaling mechanisms involved in the circadian clock.

PMID- 12002160
TI  - Translational and transcriptional inhibitors block serotonergic phase advances of
      the suprachiasmatic nucleus circadian pacemaker in vitro.
AB  - The mammalian circadian pacemaker is located in the suprachiasmatic nucleus
      (SCN). Various inputs modulate pacemaker phase, including the serotonergic
      (5HTergic) input from the midbrain raphe. 5HT phase-advances the SCN pacemaker
      when applied during mid subjective day. In vitro studies indicate that 5HT
      advances the mammalian circadian pacemaker through a process that includes
      stimulating 5HT7 receptors, activating protein kinase A, and opening K+ channels.
      How these cytoplasmic and membrane events translate into a shift in the molecular
      core of the circadian oscillator is not known. To further understand this
      process, the authors investigated whether 5HTergic phase advances require
      transcription or translation. Using two reversible translational inhibitors,
      anisomycin and cycloheximide, the authors show that inhibiting protein synthesis
      blocks 5HTergic phase shifts. The authors further show that the transcriptional
      inhibitor 5,6-dichloro-1-beta-ribobenzimidazole also blocks 5HTergic phase
      shifts. These results are similar to those found previously with respect to
      5HTergic modulation of the Aplysia ocular circadian clock, and suggest that 5HT
      may phase-shift the SCN pacemaker through increasing transcription and
      translation of specific proteins.

PMID- 12002161
TI  - Photoperiod-dependent response to androgen in the medial amygdala of the Siberian
      hamster, Phodopus sungorus.
AB  - The medial nucleus of the amygdala (MeA) is a steroid-sensitive region that has
      been implicated in the expression of behaviors such as mating and aggression. The
      male Siberian hamster (Phodopus sungorus) uses light cues to regulate its
      reproductive neuroendocrine system, reducing androgen synthesis in the autumn and
      increasing it in the spring. There is also evidence that short photoperiods
      reduce the sensitivity of the brain to the behavioral effects of androgen. The
      authors tested the hypothesis that MeA neurons are less responsive to androgen in
      short photoperiods by comparing the regional volume and average soma size of the
      four MeA subnuclei (anterodorsal [MeAD], anteroventral [MeAV], posterodorsal
      [MePD], and posteroventral) in adult male hamsters that had been castrated and
      then implanted with capsules containing either testosterone (T) or nothing.
      Animals from each group were housed in either long or short photoperiods for 15
      weeks. MeAD and MeAV somata displayed photoperiod-dependent responses to
      androgen, increasing in size after T treatment only in long days. In contrast,
      the average soma size and the regional volume of the MePD subnucleus were
      significantly larger in T-treated males regardless of photoperiod. The authors
      conclude that photoperiod influences the sensitivity of the MeA to androgen.

PMID- 12002162
TI  - Seasonal weight regulation of the raccoon dog (Nyctereutes procyonoides):
      interactions between melatonin, leptin, ghrelin, and growth hormone.
AB  - The raccoon dog (Nyctereutes procyonoides, Canidae, Carnivora) is a middle-sized
      omnivore with excessive autumnal fattening and winter sleep. We studied seasonal
      weight regulation of the species by following the plasma leptin, ghrelin, and
      growth hormone (GH) levels of farm-bred raccoon dogs (n = 32) for 6 months. In
      August, half of the raccoon dogs received continuous-release melatonin implants,
      and in November, half of the animals of both the sham-operated and melatonin
      treated groups were fasted for 2 months. In the autumn, the plasma leptin and GH
      levels were low, but the ghrelin levels were relatively high and correlated
      positively with energy intake. This represents the period of energy storage.
      Leptin and GH levels peaked simultaneously in late October, and melatonin
      advanced the peaks by 1 week. Thereafter, the levels rapidly declined,
      representing the transition period from autumnal anabolism to wintertime
      catabolism. In the winter, the leptin and GH levels rose to high levels, but the
      ghrelin-leptin ratio was very low. This is the period of winter sleep, with fat
      accumulated in the autumn as the principal metabolic fuel. In the winter, leptin,
      ghrelin, and GH may work in synergy to increase lipolysis. GH may also induce
      winter sleep to the raccoon dog. Fasting had no effect on the hormone levels,
      unlike in humans and rodents. Instead of the amount of fat in the body, the main
      regulators of the levels of these hormones in the raccoon dog are presumably
      seasonal rhythms entrained by melatonin.

PMID- 12002163
TI  - Stress-induced hyperthermia depends on both time of day and light condition.
AB  - Rats placed in an environment other than their home cage increase their body
      temperature (Tb) by more than 1 degree C. This stress-induced hyperthermia is
      considered to be a fever, in the sense that the Tb rise seems to reflect an
      upward shift in the level of regulated Tb (set point). The circadian rhythm of Tb
      also reflects changes in set point. One might therefore expect to see differences
      in response to such stress during various phases of the light-dark (LD) cycle as
      Tb fluctuates between L and D. To test this, 3- to 6-month-old male Long-Evans
      rats were taken from their home cages (12:12 LD) and placed individually in a
      Plexiglas container for 30 min. Tb and activity were measured via telemetry. In
      the first experiment, rats were placed in the container during day (from 1 to 3 h
      after lights on) and night (from 1 to 3 h after lights off), with light on or off
      during the test. There was a significant Tb rise in response to placement in the
      container at all times except when the rats were tested during the night with
      light on in the container; in that condition there was no Tb rise. In the second
      experiment, the authors determined that 30 min of light in the home cage before
      the test did not affect Tb: If the light was on in the test situation,
      hyperthermia was inhibited, and if it was off, hyperthermia was as high as
      control levels. In the third experiment, to determine whether this effect was
      time dependent, the test was performed at 4-h intervals, with light on or off
      during the test. The strongest inhibiting effect of light was in early night. In
      the fourth experiment, the authors turned the lights on during early night while
      the rats were in their home cages. This reduced their Tb significantly by less
      than 0.3 degrees C. The authors conclude that both clock time and light condition
      during testing are factors affecting the Tb rise in response to stress.

PMID- 12002164
TI  - Is food availability a circannual zeitgeber in tropical birds? A field experiment
      on stonechats in tropical Africa.
AB  - Equatorial stonechats (Saxicola torquata axillaris) in Africa are seasonal
      breeders like their temperate-zone conspecifics (S.t. rubicola). Their annual
      cycle in gonadal size and function is controlled by an endogenous circannual
      rhythmicity that has been shown to run for up to 10 years in a constant
      equatorial photoperiod under laboratory conditions, with a period deviating from
      12 months. In nature, however, this rhythm is synchronized with the actual year.
      Because photoperiod is essentially constant at the equator, it is likely that
      other environmental factors act as zeitgebers. The authors test whether food
      availability affects reproductive cycles of free-living East African stonechats.
      The authors offered supplemental food to the birds 2 months before the regular
      onset of the breeding season. Supplementally fed males started to sing and
      display earlier than males of control pairs that did not receive extra food.
      Although the supplemented food advanced the onset of the breeding season in the
      pairs that were fed, the onset of the postnuptial molt following the breeding
      season was not correspondingly shifted. Furthermore, in the year following the
      experiment, all pairs initiated breeding at the same time. The authors conclude
      that food availability does not act as a zeitgeber, but rather as a factor that
      modifies the timing of reproduction without affecting the underlying rhythmicity.
      The authors propose that this is adaptive under environmental conditions that are
      relatively constant within a given year but may vary considerably between years.
      The zeitgeber synchronizing the endogenous rhythmicity remains to be identified.

PMID- 12002165
TI  - Comparisons of the variability of three markers of the human circadian pacemaker.
AB  - A circadian pacemaker within the central nervous system regulates the
      approximately 24-h physiologic rhythms in sleep cycles, hormone secretion, and
      other physiologic functions. Because the pacemaker cannot be examined directly in
      humans, markers of pacemaker function must be used to study the pacemaker and its
      response to environmental stimuli. Core body temperature (CBT), plasma cortisol,
      and plasma melatonin are three marker variables frequently used to estimate the
      phase of the human pacemaker. Measurements of circadian phase using markers can
      contain variability due to the circadian pacemaker itself, the intrinsic
      variability of the marker relative to the pacemaker, the method of analysis of
      the marker, and the marker assay. For this report, we compared the mathematical
      variability of a number of methods of identifying circadian phase from CBT,
      plasma cortisol, and plasma melatonin data collected in a protocol in which
      pacemaker variability was minimized using low light levels and regular timing of
      both the light pattern and the rest/activity schedule. We hoped to assess the
      relative variabilities of the different physiological markers and the analysis
      methods. Methods were based on the crossing of an absolute threshold, on the
      crossing of a relative threshold, or on fitting a curve to all data points. All
      methods of calculating circadian phase from plasma melatonin data were less
      variable than those calculated using CBT or cortisol data. The standard deviation
      for the phase estimates using CBT data was 0.78 h, using cortisol data was 0.65
      h, and for the eight analysis methods using melatonin data was 0.23 to 0.35 h.
      While the variability for these markers might be different for other subject
      populations and/or less stringent study conditions, assessment of the intrinsic
      variability of the different calculations of circadian phase can be applied to
      allow inference of the statistical significance of phase and phase shift
      calculations, as well as estimation of sample size or statistical power for the
      number of subjects within an experimental protocol.

PMID- 12002166
TI  - Peer review my foot!

PMID- 12002167
TI  - Enterobacter sakazakii infections associated with the use of powdered infant
      formula--Tennessee, 2001.
AB  - Enterobacter sakazakii, a gram-negative, rod-shaped bacterium, is a rare cause of
      invasive infection with high death rates in neonates. This report summarizes the
      investigation of a fatal infection associated with E. sakazakii in a hospitalized
      neonate, which indicated that the infection was associated with the presence of
      the organism in commercial powdered formula fed to the infant. The implicated
      batch of formula has been recalled by the manufacturer. Clinicians should be
      aware of the potential risk for infection from use of nonsterile enteral formula
      in the neonatal health-care setting.

PMID- 12002168
TI  - Annual smoking-attributable mortality, years of potential life lost, and economic
      costs--United States, 1995-1999.
AB  - Cigarette smoking is the leading cause of preventable death in the United States
      and produces substantial health-related economic costs to society. This report
      presents the annual estimates of the disease impact of smoking in the United
      States during 1995-1999. CDC calculated national estimates of annual smoking
      attributable mortality (SAM), years of potential life lost (YPLL), smoking
      attributable medical expenditures (SAEs) for adults and infants, and productivity
      costs for adults. Results show that during 1995-1999, smoking caused
      approximately 440,000 premature deaths in the United States annually and
      approximately $157 billion in annual health-related economic losses.
      Implementation of comprehensive tobacco-control programs as recommended by CDC
      could effectively reduce the prevalence, disease impact, and economic costs of
      smoking.

PMID- 12002169
TI  - Traumatic brain injury among American Indians/Alaska Natives--United States, 1992
      1996.
AB  - Traumatic Brain Injury (TBI) is a major cause of morbidity and mortality in the
      United States, resulting in approximately 52,000 deaths, 230,000
      hospitalizations, and 80,000 disabilities annually. Among American Indians/Alaska
      Natives (AI/ANs), injuries are the second leading cause of death; however, few
      published reports concern nonfatal injuries in this population, especially for
      injuries such as TBI. To describe the causes and impact of TBI among AI/ANs, CDC
      analyzed Indian Health Service (IHS) hospital discharge data. This report
      summarizes the results of this analysis, which indicate that prevention
      strategies should focus on the leading causes of TBI hospitalizations, including
      motor-vehicle crashes, assaults, and falls.

PMID- 12002170
TI  - Progress toward poliomyelitis eradication--Egypt, 2001.
AB  - The 1988 World Health Assembly resolved to eradicate poliomyelitis worldwide by
      2000. Since then, the estimated number of polio cases has decreased by >99%. The
      Americas and the Western Pacific regions of the World Health Organization (WHO)
      have been certified polio-free, and it is expected that the European Region will
      be certified this year. Progress also has been made in the Eastern Mediterranean
      Region (EMR), where polio is endemic in five of 22 countries (Afghanistan, Egypt,
      Pakistan, Somalia, and Sudan). This report summarizes progress toward polio
      eradication from 1997 through 2001 in Egypt, where several independent chains of
      wild poliovirus type 1 continue to circulate despite a long history of
      eradication efforts. The findings indicate the need to improve surveillance and
      vaccination activities.

PMID- 12002171
TI  - Prevention and control of influenza. Recommendations of the Advisory Committee on
      Immunization Practices (ACIP).
AB  - This report updates the 2001 recommendations by the Advisory Committee on
      Immunization Practices (ACIP) regarding the use of influenza vaccine and
      antiviral agents (MMWR 2001;50 [No. RR-4]:1-44). The 2002 recommendations include
      new or updated information regarding 1) the timing of influenza vaccination by
      risk group; 2) influenza vaccine for children aged 6-23 months; 3) the 2002-2003
      trivalent vaccine virus strains: A/Moscow/10/99 (H3N2)-like, A/New
      Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like strains; and 4)
      availability of certain influenza vaccine doses with reduced thimerosal content.
      A link to this report and other information related to influenza can be accessed
      at the website for the Influenza Branch, Division of Viral and Rickettsial
      Diseases, National Center for Infectious Diseases, CDC, at
      http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm.

PMID- 12002172
TI  - Dipole models for the EEG and MEG.
AB  - The current dipole is a widely used source model in forward and inverse
      electroencephalography and magnetoencephalography applications. Analytic
      solutions to the governing field equations have been developed for several
      approximations of the human head using ideal dipoles as the source model. Numeric
      approaches such as the finite-element and finite-difference methods have become
      popular because they allow the use of anatomically realistic head models and the
      increased computational power that they require has become readily available.
      Although numeric methods can represent more realistic domains, the sources in
      such models are an approximation of the ideal dipole. In this paper, we examine
      several methods for representing dipole sources in finite-element models and
      compare the resulting surface potentials and external magnetic field with those
      obtained from analytic solutions using ideal dipoles.

PMID- 12002173
TI  - The oral glucose minimal model: estimation of insulin sensitivity from a meal
      test.
AB  - Recently, a new approach has been proposed to estimate insulin sensitivity (S(I))
      from an oral glucose tolerance test or a meal using an "integral equation". Here,
      we improve on the "integral equation" by resorting to a "differential equation"
      approach. The classic glucose kinetics minimal model was used with the addition
      of a parametric model for the rate of appearance into plasma of oral glucose
      (Ra). Three behavioral models of Ra were proposed: piecewise-linear (P), spline
      (S) and dynamic (D). All three models performed satisfactorily allowing a precise
      estimation of S(I) and a plausible reconstruction of Ra. Mean S(I) estimates were
      virtually identical: S(I)P = 6.81 +/- 0.87 (SE); S(I)S = 6.53 +/- 0.80; and S(I)D
      = 6.62 +/- 0.79. S(I) strongly correlated with the integral-equation index (I)
      S(I)I: r = 0.99, p < 0.01 for models D and S, and r 0.97, p < 0.01 for P. Also,
      SI compared well with insulin sensitivity estimated from intravenous glucose
      tolerance test in the same subjects (r = 0.75, p < 0.01; r = 0.71, p < 0.01; r =
      0.73, p < 0.01, respectively, for P, S, and D models versus s(I)IVGTT). Finally,
      the novel approach allows estimation of SI from a shorter test (120 min): model P
      yielded S(I)R = 7.16 +/- 1.0 (R for reduced) which correlated very well with
      S(I)P and S(I)I (respectively, r = 0.94, p < 0.01; r = 0.95, p < 0.01) and still
      satisfactorily with S(I)IVGTT (r = 0.77, p < 0.01).

PMID- 12002174
TI  - Simulation and prediction of cardiotherapeutical phenomena from a pulsatile model
      coupled to the Guyton circulatory model.
AB  - In order to use simulation prediction for cardiotherapeutical purposes, the well
      documented and physiologically validated circulatory Guyton model was coupled to
      a cardiac pulsatile model which comprises the hemodynamics of the four chambers
      including valvular effects, as well as the Hill, Frank-Starling, Laplace, and
      autonomic nervous system (ANS) effects. The program is written in the "C"
      language and available for everybody. The program system was submitted to
      validation and plausibility tests both as to the steady-state and the dynamic
      properties. Pressures, volumes and flows and other variables turned out to be
      compatible with published experimental and clinical recordings both under
      physiological and pathophysiological conditions. The results from the application
      to cardiac electrotherapy emphasize the importance of atrial contraction to
      ventricular filling, the adequate atrio-ventricular delay, the effect of impaired
      ventricular relaxation, and the significance of the choice of the adequate
      cardiac pacemaker, both with respect to the stimulation site and the adequate
      sensor controlling pacing rate. The simulation will be further developed, tested
      and applied for cardiological purposes.

PMID- 12002175
TI  - Arterial pulse wave reflection as feedback.
AB  - Traditionally, input impedance (Z(in)) has been used to characterize the global
      dynamic properties of an arterial system independent of properties of the heart.
      Defined as the relationship of pressure and flow at the entrance of an arterial
      system, it describes the ability of an arterial system to dynamically impede
      blood flow. Recently, a new description has been developed that also
      characterizes the arterial system independent of properties of the heart.
      Apparent arterial compliance (C(app)) is defined as the dynamic relationship of
      input pressure and volume stored in an arterial system, and describes the ability
      of the arterial system to dynamically store blood. Both Z(in) and C(app) are
      influenced by pulse wave propagation and reflection. However, the functional form
      of Capp lends itself to describing the arterial system in terms of negative
      feedback. Pulse wave reflection decreases the pulsatile volume stored (gain) at
      low frequencies, but increases the range of frequencies (bandwidth) in which the
      pulsatile volume is determined by total arterial compliance. This paper
      illustrates, by simple analytical formula, large-scale arterial system modeling,
      and direct analysis of data, how this conceptualization of reflection offers a
      new means to interpret changes in arterial system dynamics resulting from changes
      in arterial compliance.

PMID- 12002176
TI  - A multiple-layer finite-element model of the surface EMG signal.
AB  - The effect of skin, muscle, fat, and bone tissue on simulated surface
      electromyographic (EMG) signals was examined using a finite-element model. The
      amplitude and frequency content of the surface potential were observed to
      increase when the outer layer of a homogeneous muscle model was replaced with
      highly resistive skin or fat tissue. The rate at which the surface potential
      decreased as the fiber was moved deeper within the muscle also increased.
      Similarly, the rate at which the surface potential decayed around the surface of
      the model, for a constant fiber depth, increased. When layers of subcutaneous fat
      of increasing thickness were then added to the model, EMG amplitude, frequency
      content, and the rate of decay of the surface EMG signal around the limb
      decreased, due to the increased distance between the electrodes and the active
      fiber. The influence of bone on the surface potential was observed to vary
      considerably, depending on its location. When located close to the surface of the
      volume conductor, the surface EMG signal between the bone and the source and
      directly over the bone increased, accompanied by a slight decrease on the side of
      the bone distal to the active fiber. The results emphasize the importance of
      distinguishing between the effects of material properties and the distance
      between source and electrode when considering the influence of subcutaneous
      tissue, and suggest possible distortions in the surface EMG signal in regions
      where a bone is located close to the skin surface.

PMID- 12002177
TI  - A computer-aided detection of EEG seizures in infants: a singular-spectrum
      approach and performance comparison.
AB  - This paper presents a scalp electroencephalogram (EEG) seizure detection scheme
      based on singular spectrum analysis (SSA) and Rissanen minimum description length
      (MDL) model-order selection (SSA-MDL). Preprocessing of the signals allows for
      the drastic reduction of the number of false alarms. Statistical performance
      comparison with seizure detection schemes of Gotman et al. and Liu et al. is
      performed on both synthetic data and real EEG seizures. Monte Carlo simulations
      based on synthetic infant EEG seizure data reveals some detection drawbacks on a
      large variety of seizure waveforms. Detection using both Monte Carlo and four
      real infant scalp EEG signals shows the superiority of the SSA-MDL method with an
      average good detection rate of >93% and false detection rate <4%.

PMID- 12002178
TI  - Frequency-related effects in the optimization of coils for the magnetic
      stimulation of the nervous system.
AB  - Magnetic stimulation of the nervous system is a non-invasive technique with a
      large number of applications in neurological diagnosis, brain research, and,
      recently, therapy. New applications require engineering modifications in order to
      decrease power consumption and coil heating. This can be accomplished by
      optimized coils with minimized resistance. In this study the influence of some
      frequency-related effects (skin and proximity effect) on the coil resistance will
      be discussed, together with the role played by wire shape, wire section, and
      twisting effect. The results show that the coil resistance increases with
      frequency. As an example, for a 20-mm2 circular wire section, the skin effect in
      the typical frequency range of magnetic stimulator devices (2-4 kHz) increases
      the coil resistance up to about 45% with respect to its dc value. Moreover, the
      influence of the frequency is lower for flat wire sections and reasonably small
      helix twist angle of the coil.

PMID- 12002179
TI  - In-vivo measurement of swine myocardial resistivity.
AB  - We used a four-terminal plunge probe to measure myocardial resistivity in two
      directions at three sites from the epicardial surface of eight open-chest pigs in
      vivo at eight frequencies ranging from 1 Hz to 1 MHz. We calibrated the plunge
      probe to minimize the error due to stray capacitance between the measured subject
      and ground. We calibrated the probe in saline solutions contained in a metal cup
      situated near the heart that had an electrical connection to the pig's heart. The
      mean of the measured myocardial resistivity was 319 ohm x cm at 1 Hz down to 166
      ohm x cm at 1 MHz. Statistical analysis showed the measured myocardial
      resistivity of two out of eight pigs was significantly different from that of
      other pigs. The myocardial resistivity measured with the resistivity probe
      oriented along and across the epicardial fiber direction was significantly
      different at only one out of the eight frequencies. There was no significant
      difference in the myocardial resistivity measured at different sites.

PMID- 12002180
TI  - Error analysis of tissue resistivity measurement.
AB  - We identified the error sources in a system for measuring tissue resistivity at
      eight frequencies from 1 Hz to 1 MHz using the four-terminal method. We expressed
      the measured resistivity with an analytical formula containing all error terms.
      We conducted practical error measurements with in-vivo and bench-top experiments.
      We averaged errors at all frequencies for all measurements. The standard
      deviations of error of the quantization error of the 8-bit digital oscilloscope
      with voltage averaging, the nonideality of the circuit, the in-vivo motion
      artifact and electrical interference combined to yield an error of +/- 1.19%. The
      dimension error in measuring the syringe tube for measuring the reference saline
      resistivity added +/- 1.32% error. The estimation of the working probe constant
      by interpolating a set of probe constants measured in reference saline solutions
      added +/- 0.48% error. The difference in the current magnitudes used during the
      probe calibration and that during the tissue resistivity measurement caused +/-
      0.14% error. Variation of the electrode spacing, alignment, and electrode surface
      property due to the insertion of electrodes into the tissue caused +/- 0.61%
      error. We combined the above errors to yield an overall standard deviation error
      of the measured tissue resistivity of +/- 1.96%.

PMID- 12002181
TI  - Comments on "theoretical model for an MRI radio frequency resonator".
AB  - In contrast to a previous report [Baertlein et al. (2000)], the transverse
      electomagnetic resonator used in magnetic resonance imaging is shown to be
      similar to the high-pass "birdcage" resonator in having an electric field minimum
      in correspondence with the maximum of the magnetic field. The noise performance
      of each resonator will, in consequence, be comparable, since at high frequencies
      patient conductive losses are predominant.

PMID- 12002182
TI  - A low-cost neurostimulator with accurate pulsed-current control.
AB  - A constant-current stimulator for high-impedance loads using only low-cost
      standard high-voltage components is presented. A voltage-regulator powers an
      oscillator built across the primary of a step-up transformer whose secondary
      supplies, after rectification, the high voltage to a switched current-mirror in
      the driving stage. Adjusting the regulated voltage controls the pulsed-current
      intensity. A prototype produces stimulus of amplitude and pulsewidth within 0 <
      or = I(skin) < or = 20 mA and 50 micros < or = T(pulse) < or = 1 ms,
      respectively. Pulse-repetition spans from 1 Hz to 10 Hz. Worst case ripple is
      3.7% at I(skin) = 1 mA. Overall consumption is 5.6 W at I(skin) = 20 mA.

PMID- 12002183
TI  - Data sets for estimating precision does present a number of challenges.

PMID- 12002184
TI  - A method for predicting the performance of packed columns operating with a
      reactive scrubbing liquid that control gaseous air pollutants.
AB  - A method for predicting the performance of packed columns that control gaseous
      air pollutants has been developed that exploits the advances in both computer
      software and hardware commonly used by practicing engineers. The solution of the
      simultaneous partial differential equations that describe the absorption process
      in packed columns that occurs in the presence of chemical reaction is obtained by
      converting the partial differential equations to systems of ordinary differential
      equations. These systems of ordinary differential equations are then solved using
      the method of lines along with a variable step, variable order numerical method.
      The method is applicable to systems in which there are multiple reactions within
      the liquid phase. The reactions can be of any order and can be reversible. The
      programming is simple and the machine running time is minimal. The method is
      illustrated here with an example.

PMID- 12002185
TI  - Degradation characteristics of toluene, benzene, ethylbenzene, and xylene by
      Stenotrophomonas maltophilia T3-c.
AB  - Stenotrophomonas maltophilia T3-c, isolated from a biofilter for the removal of
      benzene, toluene, ethylbenzene, and xylene (BTEX), could grow in a mineral salt
      medium containing toluene, benzene, or ethylbenzene as the sole source of carbon.
      The effect of environmental factors such as initial toluene mass, medium pH, and
      temperature on the degradation rate of toluene was investigated. The cosubstrate
      interactions in the BTEX mixture by the isolate were also studied. Within the
      range of initial toluene mass (from 23 to 70 pmol), an increased substrate
      concentration increased the specific degradation of toluene by S. maltophilia T3
      c. The toluene degradation activity of S. maltophilia T3-c could be maintained at
      a broad pH range from 5 to 8. The rates at 20 and 40 degrees C were 43 and 83%,
      respectively, of the rate at 30 degrees C. The specific degradation rates of
      toluene, benzene, and ethylbenzene by strain T3-c were 2.38, 4.25, and 2.06
      micromol/g-DCW/hr. While xylene could not be utilized as a growth substrate by S.
      maltophilia T3-c, the presence of toluene resulted in the cometabolic degradation
      of xylene. The specific degradation rate of toluene was increased by the presence
      of benzene, ethylbenzene, or xylene in binary mixtures. The presence of toluene
      or xylene in binary mixtures with benzene increased the specific degradation rate
      of benzene. The presence of ethylbenzene in binary mixtures with benzene
      inhibited benzene degradation. The presence of more than three kinds of
      substrates inhibited the specific degradation rate of benzene. All BTEX mixtures,
      except tri-mixtures of benzene, ethylbenzene, and xylene or mixtures of all four
      substrates, had little effect on the degradation of ethylbenzene by S.
      maltophilia T3-c. The utilization preference of the substrates by S. maltophilia
      T3-c was as follows: ethylbenzene was degraded fastest, followed by toluene and
      benzene. However, the specific degradation rates of substrates, in order, were
      benzene, toluene, and ethylbenzene.

PMID- 12002186
TI  - Modeling and spatially distributing forest net primary production at the regional
      scale.
AB  - Forest, agricultural, rangeland, wetland, and urban landscapes have different
      rates of carbon sequestration and total carbon sequestration potential under
      alternative management options. Changes in the proportion and spatial
      distribution of land use could enhance or degrade that area's ability to
      sequester carbon in terrestrial ecosystems. As the ecosystems within a landscape
      change due to natural or anthropogenic processes, they may go from being a carbon
      sink to a carbon source or vice versa. Satellite image analysis has been tested
      for timely and accurate measurement of spatially explicit land use change and is
      well suited for use in inventory and monitoring of terrestrial carbon. The
      coupling of Landsat Thematic Mapper (TM) data with a physiologically based forest
      productivity model (PnET-II) and historic climatic data provides an opportunity
      to enhance field plot-based forest inventory and monitoring methodologies. We use
      periodic forest inventory data from the U.S. Department of Agriculture (USDA)
      Forest Service's Forest Inventory and Analysis (FIA) Program to obtain estimates
      of forest area and type and to generate estimates of carbon storage for
      evergreen, deciduous, and mixed-forest classes. The area information is used in
      an accuracy assessment of remotely sensed forest cover at the regional scale. The
      map display of modeled net primary production (NPP) shows a range of forest
      carbon storage potentials and their spatial relationship to other landscape
      features across the southern United States. This methodology addresses the
      potential for measuring and projecting forest carbon sequestration in the
      terrestrial biosphere of the southern United States.

PMID- 12002187
TI  - Surface flux measurements of CO2 and N2O from a dried rice paddy in Japan during
      a fallow winter season.
AB  - The CO2 and N2O soil emissions at a rice paddy in Mase, Japan, were measured by
      enclosures during a fallow winter season. The Mase site, one of the AsiaFlux
      Network sites in Japan, has been monitored for moisture, heat, and CO2 fluxes
      since August 1999. The paddy soil was found to be a source of both CO2 and N2O
      flux from this experiment. The CO2 and N2O fluxes ranged from -27.6 to 160.4
      microg CO2/m2/sec (average of 49.1 +/- 42.7 microg CO2/m2/sec) and from -4.4 to
      129.5 ng N2O/m2/sec (average of 40.3 +/- 35.6 ng N2O/m2/ sec), respectively. A
      bimodal trend, which has a sub-peak in the morning around 10:00 a.m. and a
      primary peak between 2:00 and 3:00 p.m., was observed. Gas fluxes increased with
      soil temperature, but this temperature dependency seemed to occur only on the
      calm days. Average CO2 and N2O fluxes were 27.7 microg CO2/m2/sec and 13.4 ng
      N2O/m2/sec, with relatively small fluctuation during windy days, while averages
      of 69.3 microg CO2/m2/sec and 65.8 ng N2O/m2/sec were measured during calm days.
      This relationship was thought to be a result of strong surface winds, which
      enhance gas exchange between the soil surface and the atmosphere, thus reducing
      the gas emissions from soil surfaces.

PMID- 12002188
TI  - Spatial differences in outdoor PM10 mass and aerosol composition in Mexico City.
AB  - Twenty-five MiniVol samplers were operated throughout the Mexico City
      metropolitan region from February 22 through March 22, 1997, to evaluate the
      variability of PM10 concentrations and composition. The highest PM10
      concentrations were found in neighborhoods with unpaved or dirty roads, and
      elements related to crustal material were the main cause of differences from
      nearby (<200 m) monitors that were not adjacent to the roadbed. SO4(2-)
      concentrations were homogeneous across the city. SO4(2-) measured at the city
      boundaries was about two-thirds of the concentrations measured within the
      urbanized area, indicating that most SO4(2-) is of regional origin. Elemental
      carbon (EC) and organic carbon (OC) concentrations were highly variable, with
      higher concentrations in areas that had high diesel traffic and older vehicles.
      Spatial correlations among PM10 concentrations were high, even though absolute
      concentrations were variable, indicating a common effect of meteorology on the
      concentration or dispersion of local emissions.

PMID- 12002189
TI  - Quantification of variability and uncertainty in lawn and garden equipment NOx
      and total hydrocarbon emission factors.
AB  - Variability refers to real differences in emissions among multiple emission
      sources at any given time or over time for any individual emission source.
      Variability in emissions can be attributed to variation in fuel or feedstock
      composition, ambient temperature, design, maintenance, or operation. Uncertainty
      refers to lack of knowledge regarding the true value of emissions. Sources of
      uncertainty include small sample sizes, bias or imprecision in measurements,
      nonrepresentativeness, or lack of data. Quantitative methods for characterizing
      both variability and uncertainty are demonstrated and applied to case studies of
      emission factors for lawn and garden (L&G) equipment engines. Variability was
      quantified using empirical and parametric distributions. Bootstrap simulation was
      used to characterize confidence intervals for the fitted distributions. The 95%
      confidence intervals for the mean grams per brake horsepower/hour (g/hp-hr)
      emission factors for two-stroke engine total hydrocarbon (THC) and NOx emissions
      were from -30 to +41% and from -45 to +75%, respectively. The confidence
      intervals for four-stroke engines were from -33 to +46% for THCs and from -27 to
      +35% for NOx. These quantitative measures of uncertainty convey information
      regarding the quality of the emission factors and serve as a basis for
      calculation of uncertainty in emission inventories (EIs).

PMID- 12002190
TI  - The utilization of catalyst sorbent in scrubbing acid gases from incineration
      flue gas.
AB  - Catalyst sorbents based on alumina-supported CuO, CeO2, and CuO-CeO2 were applied
      to a dry scrubber to clean up the SO2/HCl/NO simultaneously from pilot-scale
      fluidized-bed incineration flue gas. In the presence of organic compounds, CO and
      the submicron particles SO2 and HCI removed by the fresh catalyst sorbents and NO
      reduced to N2 by NH3 under the catalysis of fresh and spent
      desulfurization/dechloridization (DeSO2/DeHCl) catalyst sorbents (copper
      compounds, Cu, CuO, and CuSO4) were evaluated in this paper. The fresh and spent
      catalyst sorbents were characterized by the Brunner-Emmett-Teller method (BET), X
      ray powder diffraction (XRPD), scanning electron microscopy (SEM), inductively
      coupled plasma-mass spectrometry (ICP-MS), and the elemental analyzer (EA). The
      study showed that the performances of CuO, CeO2, and CuO-CeO2/gamma-Al2O3 were
      better than that of Ca(OH)2. The removal efficiency of SO2 and HCl was 80-95% in
      the dry scrubber system. Under NH3/NO = 1, NO could not be reduced to N2 because
      it was difficult to control the ratio of air/fuel in the flue gas. For estimating
      the feasibility of regenerating the spent catalyst sorbents, BET and EA analyses
      were used. They indicated that the pore structures were nearly maintained and a
      small amount of carbon accumulated on their surface.

PMID- 12002191
TI  - Wet scrubber analysis of volatile organic compound removal in the rendering
      industry.
AB  - The promulgation of odor control rules, increasing public concerns, and U.S.
      Environmental Protection Agency (EPA) air regulations in nonattainment zones
      necessitates the remediation of a wide range of volatile organic compounds (VOCs)
      generated by the rendering industry. Currently, wet scrubbers with oxidizing
      chemicals are used to treat VOCs; however, little information is available on
      scrubber efficiency for many of the VOCs generated within the rendering process.
      Portable gas chromatography/mass spectrometry (GC/MS) units were used to rapidly
      identify key VOCs on-site in process streams at two poultry byproduct rendering
      plants. On-site analysis was found to be important, given the significant
      reduction in peak areas if samples were held for 24 hr before analysis. Major
      compounds consistently identified in the emissions from the plant included
      dimethyl disulfide, methanethiol, octane, hexanal, 2-methylbutanal, and 3
      methylbutanal. The two branched aldehydes, 2-methylbutanal and 3-methylbutanal,
      were by far the most consistent, appearing in every sample and typically the
      largest fraction of the VOC mixture. A chlorinated hydrocarbon, methanesulfonyl
      chloride, was identified in the outlet of a high-intensity wet scrubber, and
      several VOCs and chlorinated compounds were identified in the scrubbing solution,
      but not on a consistent basis. Total VOC concentrations in noncondensable gas
      streams ranged from 4 to 91 ppmv. At the two plants, the odor-causing compound
      methanethiol ranged from 25 to 33% and 9.6% of the total VOCs (v/v). In one
      plant, wet scrubber analysis using chlorine dioxide (ClO2) as the oxidizing agent
      indicated that close to 100% of the methanethiol was removed from the gas phase,
      but removal efficiencies ranged from 20 to 80% for the aldehydes and hydrocarbons
      and from 23 to 64% for total VOCs. In the second plant, conversion efficiencies
      were much lower in a packed-bed wet scrubber, with a measurable removal of only
      dimethyl sulfide (20-100%).

PMID- 12002192
TI  - Meta-analysis of time-series studies of air pollution and mortality: effects of
      gases and particles and the influence of cause of death, age, and season.
AB  - A comprehensive, systematic synthesis was conducted of daily time-series studies
      of air pollution and mortality from around the world. Estimates of effect sizes
      were extracted from 109 studies, from single- and multipollutant models, and by
      cause of death, age, and season. Random effects pooled estimates of excess all
      cause mortality (single-pollutant models) associated with a change in pollutant
      concentration equal to the mean value among a representative group of cities were
      2.0% (95% CI 1.5-2.4%) per 31.3 microg/m3 particulate matter (PM) of median
      diameter < or = 10 microm (PM10); 1.7% (1.2-2.2%) per 1.1 ppm CO; 2.8% (2.1-3.5%)
      per 24.0 ppb NO2; 1.6% (1.1-2.0%) per 31.2 ppb O3; and 0.9% (0.7-1.2%) per 9.4
      ppb SO2 (daily maximum concentration for O3, daily average for others). Effect
      sizes were generally reduced in multipollutant models, but remained significantly
      different from zero for PM10 and SO2. Larger effect sizes were observed for
      respiratory mortality for all pollutants except O3. Heterogeneity among studies
      was partially accounted for by differences in variability of pollutant
      concentrations, and results were robust to alternative approaches to selecting
      estimates from the pool of available candidates. This synthesis leaves little
      doubt that acute air pollution exposure is a significant contributor to
      mortality.

PMID- 12002193
TI  - Screening for abuse in Spanish-speaking women.
AB  - BACKGROUND: Domestic violence is a major personal and public health concern
      affecting women of all walks of life. Physicians have reported the need for
      screening instruments to help recognize abuse; several have been validated in
      English. No screening tools thus far have been validated in other languages.
      METHODS: We translated a previously validated tool, the Woman Abuse Screening
      Tool (WAST), into Spanish. To assess for validity, we compared responses of
      Spanish-speaking abused and nonabused respondents drawn from a community health
      center and a battered women's shelter. There were 27 women in the abused group
      and 34 women in the nonabused comparison group. RESULTS: The scale was found to
      be reliable with a Cronbach alpha of 0.91. The mean WAST Spanish scores were
      significantly different between the two groups, indicating this tool would be a
      valid screening instrument. A short form using the two most reliable questions
      was developed as a more rapid screening tool for office use, achieving a
      specificity of 94% and a sensitivity of 89%. CONCLUSIONS: The Spanish version of
      the WAST successfully discriminated between Spanish-speaking nonabused and abused
      women. The short form might help physicians reliably screen for abuse in Spanish
      speaking women.

PMID- 12002194
TI  - Sun protection of children at the beach.
AB  - BACKGROUND: We wanted to determine the frequency with which sun protection
      measures are used by children at the beach. METHODS: A cross-sectional study was
      undertaken that combined a brief, structured interview with direct observation of
      the sun protection methods (sunscreen, clothing, hats, shade) used for children
      at a public beach in Florida. RESULTS: Of the 139 children observed, 97 (69.8%)
      had some form of sun protection used on all three body regions (head, torso,
      legs), while only 8 (5.8%) had none of the three body regions protected.
      Sunscreen was the most common method of sun protection (84.9%), and other methods
      were less frequently used (shirt 11.5%, pants 26.6%, hat 8.6%, shade 14.4%). Sun
      protection use differed by sex, with girls having better protection of their head
      and torso, and boys slightly better protection of their legs. CONCLUSIONS: Using
      direct observation, we found that parents frequently use sun protection measures
      (mainly sunscreen) for their children while at the beach. Parents primarily rely
      on the use of sunscreen, rather than such measures as avoiding the sun, using
      shade, or protective clothing.

PMID- 12002195
TI  - Introduction of handheld computing to a family practice residency program.
AB  - BACKGROUND: Handheld computers are valuable practice tools. It is important for
      residency programs to introduce their trainees and faculty to this technology.
      This article describes a formal strategy to introduce handheld computing to a
      family practice residency program. METHODS: Objectives were selected for the
      handheld computer training program that reflected skills physicians would find
      useful in practice. TRGpro handheld computers preloaded with a suite of medical
      reference programs, a medical calculator, and a database program were supplied to
      participants. Training consisted of four 1-hour modules each with a written
      evaluation quiz. Participants completed a self-assessment questionnaire after the
      program to determine their ability to meet each objective. RESULTS: Sixty of the
      62 participants successfully completed the training program. The mean composite
      score on quizzes was 36 of 40 (90%), with no significant differences by level of
      residency training. The mean self-ratings of participants across all objectives
      was 3.31 of 4.00. Third-year residents had higher mean self-ratings than others
      (mean of group, 3.62). Participants were very comfortable with practical skills,
      such as using drug reference software, and less comfortable with theory, such as
      knowing the different types of handheld computers available. CONCLUSION:
      Structured training is a successful strategy for introducing handheld computing
      to a residency program.

PMID- 12002196
TI  - Low-bandwidth, low-cost telemedicine consultations in rural family practice.
AB  - BACKGROUND: Telemedicine, based on the use of interactive video consultations, is
      being used more commonly in rural settings. This development is potentially
      important to rural patients because there are fewer physicians, particularly
      specialist physicians, in rural areas. Declining costs of telemedicine equipment
      and transmission have created increased access to these technologies for rural
      family physicians and their patients. METHODS: This study considers satisfaction
      levels of rural family physicians, academic-based specialists, and rural patients
      in 130 consultations between rural physicians, rural patients, and urban academic
      specialists. To increase the practicability for rural use, low-cost equipment and
      low-bandwidth digital telephone transmission lines were utilized. Data were
      collected using questionnaires that were completed by patients, family
      physicians, and specialist consultants after each consultation. RESULTS: All
      categories of participants noted very high levels of satisfaction. CONCLUSION:
      Telemedicine-based consultations are well accepted by rural patients, rural
      family physicians, and urban academic specialist consultants. This approach could
      offer a useful adjunct to rural health care.

PMID- 12002197
TI  - Sleep apnea: from the nose to the heart.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a disorder consisting of repetitive
      obstruction of the upper airway during sleep accompanied by ineffective
      respiratory effort. METHODS: We developed this clinical review using an extensive
      MEDLINE review of the literature and data from our laboratories. This review
      examines (1) the prevalence of OSA; (2) the pathophysiology involved including
      the causes of obstruction, the physiologic stimuli, and resulting autonomic
      changes; (3) the cardiovascular manifestations; and (4) the therapeutic
      approaches to patients with OSA with emphasis on arrhythmia management. RESULTS
      AND CONCLUSIONS: OSA is highly prevalent and largely underdiagnosed. As part of a
      much broader spectrum of respiratory disturbances during sleep, OSA can result in
      a multitude of systemic manifestations. Structural changes occur in the airway to
      obstruct airflow during OSA, and the resulting apnea activates hypoxic and
      hypercapnic reflexes, which in turn lead to profound elevation in sympathetic
      nerve activity and cyclical changes in parasympathetic nerve activity. These
      autonomic effects are thought to contribute to the associated cardiovascular
      diseases (eg, hypertension) and frequently observed brady- and tachyarrhythmias.
      The ultimate goal in the treatment of OSA is to restore airway patency and sleep
      continuity and to improve daytime functioning and quality of life. Treatment
      usually results in improvement of clinical symptoms.

PMID- 12002198
TI  - Early detection and treatment of neovascular age-related macular degeneration.
AB  - BACKGROUND: The neovascular form of age-related macular degeneration (AMD) can
      rapidly lead to severe loss of central vision and adversely affect the patient's
      quality of life. During the 1990s the only proven treatment for neovascular AMD
      was laser photocoagulation. Only a minority of patients are eligible to receive
      this treatment, however, and the treatment itself can cause acute retinal damage
      with immediate vision loss. Verteporfin therapy is a new treatment option
      involving photodynamic therapy that was recently shown to be relatively safe and
      effective in reducing the risk of vision loss in selected cases. METHODS: Recent
      literature was reviewed on management of choroidal neovascularization caused by
      AMD that proved beneficial in large-scale randomized clinical trials. These
      studies were selected through a MEDLINE search of files from 1982 to the present
      using the keywords "randomized clinical trials," "choroidal neovascularization,"
      and "age-related macular degeneration," as well as through personal knowledge of
      recently completed trials. RESULTS AND CONCLUSIONS: Primary care physicians can
      effect good treatment outcomes by detecting early signs of AMD and educating
      patients about the necessity of prompt referral to an ophthalmologist. Immediate
      referral is increasingly important because, compared with laser photocoagulation,
      current photodynamic therapy with verteporfin is applicable to more patients.
      Greater patient awareness of neovascular AMD and the importance of self-testing
      of vision can also be communicated to patients in primary care.

PMID- 12002199
TI  - Paroxysmal hypertension, pheochromocytoma, and pregnancy.
AB  - BACKGROUND: Hypertension is the most common medical complication of pregnancy.
      Pheochromocytoma in pregnancy is rare, and if unrecognized, can cause serious
      perinatal morbidity and mortality. METHODS: A patient with severe hypertension,
      postpartum pulmonary edema, and a recognized pheochromocytoma is described.
      RESULTS: Abdominal palpation after vaginal childbirth reproduced the diagnostic
      triad of hypertension, headaches, and palpitations. Magnetic resonance imaging
      established the correct diagnosis before biochemical confirmation of excess
      catecholamine production. The patient responded to alpha-adrenergic receptor
      blockade with control of her severe hypertension and clearing of pulmonary edema.
      The best time to diagnose a pheochromocytoma is before delivery because vaginal
      childbirth stimulates the release of lethal amounts of catecholamines.
      CONCLUSIONS: The physician who delivers babies must distinguish between labile
      hypertension and paroxysmal hypertension. Most experts believe that a spontaneous
      vaginal delivery is contraindicated when the patient has a pheochromocytoma.
      Postpartum pulmonary edema associated with a pheochromocytoma is unusual. The
      profound pressor response elicited by palpation of the postpartum abdomen, the
      failure of medications usually effective in the treatment of a hypertensive
      crisis, and the use of magnetic resonance imaging to confirm a functioning
      adrenal adenoma are the features unique to this case.

PMID- 12002200
TI  - Malaria recurrence caused by Plasmodium falciparum.

PMID- 12002201
TI  - Treatment of a young adult taking gamma-butyrolactone (GBL) in a primary care
      clinic.

PMID- 12002202
TI  - Large, complex, benign cystic teratoma in an adolescent.

PMID- 12002203
TI  - Spiritual component of patients who experience psychological trauma: family
      physician intervention.

PMID- 12002204
TI  - Role of telemedicine in the health care delivery system.

PMID- 12002205
TI  - Technical competency in flexible sigmoidoscopy.

PMID- 12002206
TI  - Clinical judgment predicts culture results in upper respiratory tract infections.
AB  - BACKGROUND: We wanted to describe the natural history, familial transmission,
      microbiology, and accuracy of clinical judgment of potential pathogens of
      respiratory tract infections in a community family practice. METHODS: The study
      was a prospective case series in which consecutive patients requesting treatment
      for respiratory tract infections were evaluated after nurse triage during 3 fall
      spring months in a solo family practice in suburban Cleveland, Ohio. According to
      the physician's usual practice, patients were classified into high-, medium-, and
      low-risk groups for bacterial illness based on their clinical signs and symptoms.
      Cultures were performed and sensitivities were determined for pathogens from the
      infected throat, nasopharynx, conjunctiva, or other sites. Patient symptoms and
      well-being were scored at the initial visit and at 3, 7 and 14 days later.
      RESULTS: There were 111 illness episodes in 86 patients; 94% had cultures taken,
      of which 38% grew a potentially pathogenic bacteria, most commonly group A
      streptococci, Branhamella catarrhalis or Staphylococcus aureus. The physician's
      judgment of bacterial infection was associated (P < .001) with having a positive
      culture (sensitivity 53%, specificity 78%, positive and negative predictive
      values 60% and 73%, respectively). A positive culture was associated with 2 of 16
      signs or symptoms: purulent discharge from any site or a red swollen eye. There
      was no association of treatment status with clinical outcomes during 2 weeks of
      follow-up observation. CONCLUSION: Infection with a potentially pathogenic
      bacteria is difficult to determine solely by clinical signs and symptoms, but
      clinical judgment is associated with positive culture results. The effect of
      selective treatment of upper respiratory tract infection based on clinical signs
      and symptoms and patient and family culture results remains to be determined, but
      using clinical judgment could result in more selective antibiotic use than found
      in current practice patterns.

PMID- 12002207
TI  - Professionalism.

PMID- 12002208
TI  - Radiologic case study. Paget's disease with a pathologic fracture.

PMID- 12002209
TI  - Anterior bone block: treatment of calcaneus deformity after failed soft-tissue
      operations.
AB  - Calcaneus deformity is almost always the result of a neural disorder. It is
      progressive, disabling, and resistant to bracing and usually requires surgery. In
      immature feet, soft-tissue operations are the procedures of choice but have the
      disadvantage of recurrence due to stretching of soft tissues. However, bony
      operations will lead to growth center damage. Anterior bone block corrects the
      deformity without damaging the growth centers.

PMID- 12002210
TI  - The mechanical effects of suture anchor insertion angle for rotator cuff repair.
AB  - Twelve matched pairs of humerii were instrumented with suture anchor at 90
      degrees, 75 degrees, 45 degrees, and 30 degrees relative to the cortical border
      at the junction of the greater tuberosity and articular surface. Two fixtures
      were inserted into each specimen at different angles and loaded to failure.
      Suture anchors failed at an average of 171, 219, 169, and 192 N with 90 degrees,
      75 degrees, 45 degrees, and 30 degrees insertion angles, respectively. No
      statistical difference was detected between groups (P=.08). Although previous
      authors have prescribed angles < or =45 degrees to improve pull-out strength, the
      current in vitro data does not support these recommendations.

PMID- 12002211
TI  - Latissimus dorsi pedicled flap for upper extremity soft-tissue reconstruction.
AB  - The latissimus dorsi often is used as a functional muscle transfer to restore
      elbow and shoulder motion. Although less common, its use as a pedicled muscle
      flap with a split-thickness skin graft provides excellent soft-tissue coverage of
      large upper extremity wounds. Seven male patients ranging in age from 6-71 years
      were treated with a pedicled latissimus dorsi muscle flap and split-thickness
      skin graft for coverage of open wounds of the shoulder, arm, or elbow with
      exposed vital structures (mean wound size: 15x10 cm). The flap also was used as a
      functional muscle transfer in one patient to replace destroyed anterior and
      middle portions of the deltoid. Wounds resulted from trauma in three patients,
      infection following trauma in two, and sarcoma excision in two. All flaps healed
      well, and donor site morbidity was minimal. At mean 16-month follow-up (range: 3
      41 months), all muscle flaps had contoured well, producing satisfactory cosmesis.
      Functional results were good, and all patients were satisfied with their outcome.
      The tendinous insertion is left intact to guard against excessive traction on the
      pedicle when the flap is used for soft-tissue coverage only.

PMID- 12002212
TI  - A comparison of the effects of solid, articulated, and posterior leaf-spring
      ankle-foot orthoses and shoes alone on gait and energy expenditure in children
      with spastic diplegic cerebral palsy.
AB  - Fourteen children with spastic diplegic cerebral palsy were evaluated wearing
      threedifferent ankle-foot orthoses and shoes alone. The ankle-foot orthoses
      included solid, articulated ankle, and posterior leaf-spring types. Evaluation
      measures included computerized gait analysis, Energy Efficiency Index data, and
      individual preference. Highly significant kinematic differences were found at the
      ankle with shoes alone approaching normative data and braces showing abnormal
      dorsiflexion. No significant differences, were found in velocity, cadence, stride
      length, or in the Energy Efficiency Index. Eight children preferred articulated
      braces, six chose posterior leaf-spring, and none chose the solid brace.

PMID- 12002213
TI  - The influence of preoperative nutritional status in wound healing after
      replacement arthroplasty.
AB  - Patient nutritional status was evaluated preoperatively using the serological
      parameters serum albumin, serum transferrin, and total lymphocyte count in 40
      patients who underwent replacement arthroplasty (33 hips and 7 knees). Using the
      standard criteria, the overall incidence of malnutrition was 40% (16 cases). Ten
      percent (4 patients) had a negative value in the Rainey McDonald nutritional
      index. On follow-up, no patient had delayed wound healing or wound infection.
      Attention to surgeon-dependent factors can offset the high risk of delayed wound
      healing imposed by patient-dependent factors.

PMID- 12002214
TI  - Arthroscopy following total knee arthroplasty.
AB  - Conservative treatment had previously been used in our institution to treat the
      painful stiff knee joint following total knee arthroplasty (TKA). However, the
      result was not satisfactory. Arthroscopic surgery was then performed in 11
      patients with painful knee joints with limited motion who had previously
      undergone TKA. Good results were achieved in eight patients. An average
      improvement of 56.3 degrees was achieved for knee range of motion. Flexion
      improved up to 90 degrees in all patients in the early postoperative period
      following arthroscopy. However, the benefits declined with time. To avoid the
      potential complications of manipulation and open arthrotomy, arthroscopic surgery
      is an option for treating the painful stiff knee joint.

PMID- 12002215
TI  - Treatment of osteoporotic ankle fractures in the elderly: surgical strategies.
AB  - The goal of displaced ankle fracture treatment is to restore congruity and
      stability to the ankle mortise. However, adequate fixation in patients with
      osteoporosis is difficult due to poorly mineralized bone. This article presents
      alternative fixation strategies that can helpachieve ankle stability in this
      patient population.

PMID- 12002216
TI  - Dyschondrosteosis.

PMID- 12002217
TI  - Bilateral posterior fracture-dislocation of the shoulder.

PMID- 12002218
TI  - Recurrence of a unicameral bone cyst after nineteen years.

PMID- 12002219
TI  - Intradural lumbar vertebral disk herniation: a case report and review.

PMID- 12002220
TI  - The computational challenges of applying comparative-based computational methods
      to whole genomes.
AB  - The explosion in genomic sequence available in public databases has resulted in
      an unprecedented opportunity for computational whole genome analyses. A number of
      promising comparative-based approaches have been developed for gene finding,
      regulatory element discovery and other purposes, and it is clear that these tools
      will play a fundamental role in analysing the enormous amount of new data that is
      currently being generated. The synthesis of computationally intensive comparative
      computational approaches with the requirement for whole genome analysis
      represents both an unprecedented challenge and opportunity for computational
      scientists. We focus on a few of these challenges, using by way of example the
      problems of alignment, gene finding and regulatory element discovery, and discuss
      the issues that have arisen in attempts to solve these problems in the context of
      whole genome analysis pipelines.

PMID- 12002221
TI  - Algorithmic strategies for the single nucleotide polymorphism haplotype assembly
      problem.
AB  - With the consensus human genome sequenced and many other sequencing projects at
      varying stages of completion, greater attention is being paid to the genetic
      differences among individuals and the abilities of those differences to predict
      phenotypes. A significant obstacle to such work is the difficulty and expense of
      determining haplotypes--sets of variants genetically linked because of their
      proximity on the genome--for large numbers of individuals for use in association
      studies. This paper presents some algorithmic considerations in a new approach
      for haplotype determination: inferring haplotypes from localised polymorphism
      data gathered from short genome 'fragments.' Formalised models of the biological
      system under consideration are examined, given a variety of assumptions about the
      goal of the problem and the character of optimal solutions. Some theoretical
      results and algorithms for handling haplotype assembly given the different models
      are then sketched. The primary conclusion is that some important simplified
      variants of the problem yield tractable problems while more general variants tend
      to be intractable in the worst case.

PMID- 12002222
TI  - Functional annotation of proteomic sequences based on consensus of sequence and
      structural analysis.
AB  - To maximise the assignment of function of the proteins encoded by a genome and to
      aid the search for novel drug targets, there is an emerging need for sensitive
      methods of predicting protein function on a genome-wide basis. GeneAtlas is an
      automated, high-throughput pipeline for the prediction of protein structure and
      function using sequence similarity detection, homology modelling and fold
      recognition methods. GeneAtlas is described in detail here. To test GeneAtlas, a
      'virtual' genome was used, a subset of PDB structures from the SCOP database, in
      which the functional relationships are known. GeneAtlas detects additional
      relationships by building 3D models in comparison with the sequence searching
      method PSI-BLAST. Functionally related proteins with sequence identity below the
      twilight zone can be recognised correctly.

PMID- 12002223
TI  - Using fold recognition to search for useful proteins: Bayesian approach to fold
      recognition.
AB  - The wealth of protein sequence and structure data is greater than ever, thanks to
      the ongoing Genomics and Structural Genomics projects. The information available
      through such efforts needs to be analysed by new methods that combine both
      databases. One important result of genomic sequence analysis is the inference of
      functional homology among proteins. Until recently sequence similarity comparison
      was the only method for homologue inference. The new fold recognition approach
      reviewed in this paper enhances sequence comparison methods by including
      structural information in the process of protein comparison. This additional
      information often allows for the detection of similarities that cannot be found
      by methods that only use sequence information.

PMID- 12002224
TI  - Application of in silico positional cloning and bioinformatic mutation analysis
      to the study of eye diseases.
AB  - A vast amount of DNA and protein sequence is now available and a plethora of
      programs have been developed to analyse the data. The bewildering variety of
      analyses that can be performed via the World-Wide Web can deter researchers from
      applying bioinformatics to augment their traditional genetic research. Focusing
      on the inherited eye diseases, this paper provides a guide to the appropriate
      software required for identification of candidate genes through to the detection
      and analysis of mutations.

PMID- 12002225
TI  - Large-scale analysis of gene expression profiles.
AB  - The accumulation of DNA microarray data has now made it possible to use gene
      expression profiles to analyse expression data. A gene expression profile
      contains the expression data for a given gene over various samples, and can be
      contrasted with an expression signature, which contains the expression data for a
      single sample. Gene expression profiles are most revealing when samples are
      grouped appropriately, either by standard clinical or pathological categories or
      by categories discovered through cluster analysis techniques. Expression profiles
      can exist at various levels of abstraction, yielding information across various
      tissues or across diseases within a particular tissue. Hypothesis tests may be
      applied to expression profiles on a large scale to identify candidate genes of
      interest.

PMID- 12002226
TI  - The role of quantitative structure--activity relationships (QSAR) in biomolecular
      discovery.
AB  - Empirical methods for building predictive models of the relationships between
      molecular structure and useful properties are becoming increasingly important.
      This has arisen because drug discovery and development have become more complex.
      A large amount of biological target information is becoming available through
      molecular biology. Automation of chemical synthesis and pharmacological screening
      has also provided a vast amount of experimental data. Tools for designing
      libraries and extracting information from molecular databases and high-throughput
      screening experiments robustly and quickly enable leads to be discovered more
      effectively. As drug leads progress down the development pipeline, the ability to
      predict physicochemical, pharmacokinetic and toxicological properties of these
      leads is becoming increasingly important in reducing the number of expensive,
      late development failures. Quantitative structure-activity relationship (QSAR)
      methods have much to offer in these areas. However, QSAR analysis has many traps
      for unwary practitioners. This review introduces the concepts behind QSAR, points
      out problems that may be encountered, suggests ways of avoiding the pitfalls and
      introduces several exciting, new QSAR methods discovered during the last decade.

PMID- 12002227
TI  - EMBOSS opens up sequence analysis. European Molecular Biology Open Software
      Suite.

PMID- 12002228
TI  - Short EMBOSS User Guide. European Molecular Biology Open Software Suite.

PMID- 12002229
TI  - Unrecognized cross-infection with vancomycin-resistant Enterococcus faccium and
      faecalis detected by molecular typing of blood isolates.

PMID- 12002230
TI  - Starting to learn about the costs of nosocomial infections in the new millennium:
      where do we go from here?

PMID- 12002231
TI  - Nonrandom selection and the attributable cost of surgical-site infections.
AB  - OBJECTIVE: To study the extent to which selection bias poses problems for
      estimating the attributable cost of deep chest surgical-site infection (SSI)
      following coronary artery bypass graft (CABG) surgery. DESIGN: Reanalysis of a
      prospective case-control study. SETTING: A large, Midwestern community medical
      center. PATIENTS: Cases were all patients who had an SSI (N = 41) following CABG
      and CABG and valve surgery between April 1996 and March 1998. Controls were every
      tenth uninfected patient (N = 160). METHODS: Estimates of the attributable cost
      of deep chest SSI were computed using unmatched comparison, matched comparison,
      linear regression, and Heckman's two-stage approach. RESULTS: The attributable
      cost of deep chest SSI was estimated to be $20,012 by unmatched comparison,
      $19,579 by matched comparison, $20,103 by linear regression, and $14,211 by
      Heckman's two-stage method. Controlling for selection bias substantially reduced
      the cost estimate, but the coefficient capturing selection bias was not
      statistically significant. CONCLUSIONS: Deep chest SSI significantly increases
      the cost of care for patients who undergo CABG surgery. Unmatched comparison,
      matched comparison, and linear regression estimated the attributable cost to be
      approximately $20,000. Although controlling for selection bias with Heckman's two
      stage method resulted in a substantially smaller estimate, the coefficient for
      selection bias was not statistically significant, suggesting that the estimates
      derived from the other models should be acceptable. However, the magnitude of the
      difference between the models shows that the effect of selection bias can be
      substantial. Some exploration for selection bias is recommended when estimating
      the attributable cost of SSIs.

PMID- 12002232
TI  - The impact of surgical-site infections following orthopedic surgery at a
      community hospital and a university hospital: adverse quality of life, excess
      length of stay, and extra cost.
AB  - OBJECTIVE: To measure the impact of orthopedic surgical-site infections (SSIs) on
      quality of life, length of hospitalization, and cost. DESIGN: A pairwise-matched
      (1:1) case-control study within a cohort. SETTING: A tertiary-care university
      medical center and a community hospital. PATIENTS: Cases of orthopedic SSIs were
      prospectively identified by infection control professionals. Matched controls
      were selected from the entire cohort of patients undergoing orthopedic surgery
      who did not have an SSI. Matching variables included type of surgical procedure,
      National Nosocomial Infections Surveillance risk index, age, date of surgery, and
      surgeon. MAIN OUTCOME MEASURES: Quality of life, duration of postoperative
      hospital stay, frequency of hospital readmission, overall direct medical costs,
      and mortality rate. RESULTS: Fifty-nine SSIs were identified. Each orthopedic SSI
      accounted for a median of 1 extra day of stay during the initial hospitalization
      (P = .001) and a median of 14 extra days of hospitalization during the follow-up
      period (P = .0001). Patients with SSI required more rehospitalizations (median, 2
      vs 1; P = .0001) and more total surgical procedures (median, 2 vs 1; P = .0001).
      The median total direct cost of hospitalizations per infected patient was
      $24,344, compared with $6,636 per uninfected patient (P = .0001). Mortality rates
      were similar for cases and controls. Quality of life was adversely affected for
      patients with SSI. The largest decrements in scores on the Medical Outcome Study
      Short Form 36 questionnaire were seen in the physical functioning and role
      physical domains. CONCLUSIONS: Orthopedic SSIs prolong total hospital stays by a
      median of 2 weeks per patient, approximately double rehospitalization rates, and
      increase healthcare costs by more than 300%. Moreover, patients with orthopedic
      SSIs have substantially greater physical limitations and significant reductions
      in their health-related quality of life.

PMID- 12002233
TI  - Hospital-acquired, laboratory-confirmed bloodstream infection: increased hospital
      stay and direct costs.
AB  - OBJECTIVES: To determine increased hospital stay and direct costs attributable to
      hospital-acquired, laboratory-confirmed bloodstream infection (BSI), and to
      evaluate the matching variable length of stay (LOS). DESIGN: Retrospective
      (historical) cohort study with 1:2 matching in intensive care units and surgical
      wards. SETTING: A 2,000-bed university hospital in Rome, Italy. PATIENTS: All
      patients admitted between January 1994 and June 1995 who had hospital-acquired,
      laboratory-confirmed BSI were considered cases; all others were eligible as
      controls. METHODS: Two controls (A and B) were selected per case in a stepwise
      fashion. Controls in group A were selected according to the following six
      criteria: ward, gender, age, diagnosis, central venous catheter, and LOS equal to
      the interval from admission to infection in a matched case +/- 20% (LOS +/- 20%).
      Controls in group B were selected according to the first five criteria, but
      excluded LOS +/- 20%. RESULTS: One hundred five of 108 patients were each matched
      with two controls. The matching appropriateness score was greater than 90%. With
      the use of controls in groups A and B, the case-fatality rates attributable to
      hospital-acquired, laboratory-confirmed BSI were 35.2% and 40.9%, respectively;
      the estimated risk ratios for death were 2.60 and 3.52 (P = .0001), respectively.
      The increased hospital stay per case attributable to hospital-acquired,
      laboratory-confirmed BSI was 19.1 (mean) and 13.0 (median) days for matched pairs
      in control group A and 19.9 (mean) and 15.0 (median) days for matched pairs in
      control group B. With controls in group A, the cost of increased hospital stay
      per patient attributable to hospital-acquired, laboratory-confirmed BSI was Euro
      15,413. The additional cost per patient due to treatment was Euro 943, making the
      overall direct cost Euro 16,356 per case. CONCLUSIONS: This study should make it
      possible to estimate the cost of hospital-acquired, laboratory-confirmed BSI in
      most hospitals after adjusting for incidence rate. It also confirmed the use of
      LOS +/- 20% as a matching variable to limit overestimation of increased hospital
      stay. To our knowledge, this is among the first such studies in Europe.

PMID- 12002234
TI  - A survey of reprocessing methods, residual viable bioburden, and soil levels in
      patient-ready endoscopic retrograde choliangiopancreatography duodenoscopes used
      in Canadian centers.
AB  - OBJECTIVES: To obtain information about current reprocessing practices and to
      obtain samples from the biopsy channel to quantitate soil levels and bioburden in
      patient-ready flexible duodenoscopes used for endoscopic retrograde
      choliangiopancreatography (ERCP). DESIGN: Participating centers were sent a
      questionnaire and a kit for on-site collection of samples from the biopsy channel
      of the duodenoscope. SETTING: Thirty-seven hospitals from across Canada
      participated. The only criterion was that they currently used and reprocessed
      flexible duodenoscopes for ERCP procedures. METHODS: The questionnaire obtained
      information on reprocessing practices. The kit included a detailed instruction
      booklet outlining sample collection and all of the tubes, sterile water, and
      brushes needed for it. Samples were collected on-site from all ERCP scopes in
      each center on Monday morning and shipped by overnight courier on ice to the
      research center. Each sample was assayed by routine microbiologic methods for
      total viable count and protein, blood, carbohydrate, and endotoxin levels.
      RESULTS: Microbial overgrowth was present in 7% of 119 scope samples. Cleaning
      appeared to be reasonably well done in most of the centers, and 43% of the
      centers were in total compliance with basic national guidelines. The data from
      the scope samples indicated that there was significantly greater buildup of
      protein, carbohydrate, and endotoxin associated with ERCP scopes from centers
      using glutaraldehyde, compared with those using peracetic acid. Carbohydrate was
      the soil component detected most frequently and in the highest concentration in
      scope channels. CONCLUSIONS: Although cleaning was generally well done, areas for
      improvement included ensuring the availability of written reprocessing protocols,
      immersion of scopes during manual cleaning, use of adequate fluid volume for
      rinsing, adequate drying of scopes prior to storage, and the separation of ERCP
      valves from scopes during storage.

PMID- 12002235
TI  - Duration of colonization with vancomycin-resistant Enterococcus.
AB  - OBJECTIVE: To determine the duration of colonization with vancomycin-resistant
      Enterococcus (VRE) and the adequacy of 3 consecutive negative cultures to
      determine clearance. DESIGN: Retrospective cohort study. SETTING: A university
      hospital. POPULATION: Patients identified by perirectal cultures as VRE carriers
      who had follow-up cultures. METHODS: Follow-up perirectal cultures were collected
      in inpatient and outpatient settings, at least 1 week apart, when patients were
      not receiving antibiotics with activity against VRE. The likelihood of culture
      positivity was analyzed given prior culture results and time from the initial
      positive culture. RESULTS: A total of 116 patients colonized with VRE had 423
      follow-up cultures, a mean of 204 days (range, 4 to 709 days) after their initial
      isolate. The first follow-up culture, collected a mean of 125 days after the
      initial positive isolate, was negative in 64%. After 1 negative follow-up
      culture, the next one was negative in 92% of the patients. After 2 negative
      cultures, 95% remained culture-negative. After 3 sequential negative cultures, 35
      (95%) of 37 patients remained culture-negative. As the interval between the
      initial and the follow-up isolates increased, the probability that a subsequent
      culture would be positive decreased (P < .001, chi square for trend). Prolonged
      hospitalization, intensive care, and antibiotic use each decreased the likelihood
      of clearing VRE. CONCLUSION: These data support the Centers for Disease Control
      and Prevention criterion of 3 sequential negative cultures, at least 1 week
      apart, to remove patients from VRE isolation. Nevertheless, this may reflect a
      decrease in the quantity of VRE to an undetectable level and these patients
      should be observed for relapse, especially when re-treated with antibiotics.

PMID- 12002236
TI  - Skin colonization by Malassezia in neonates and infants.
AB  - OBJECTIVE: To identify the timing, pattern, and determinants of colonization of
      neonates by Malassezia. DESIGN: Prospective observational study. SETTING: A
      neonatal medical and surgical unit consisting of 10 special care, 10 high
      dependency, 10 intensive care, and 10 surgical cots. PARTICIPANTS: All neonates
      (< or = 28 days of age) or infants (> 28 days of age) admitted to the unit during
      the 20-week period from October 1995 to March 1996. METHODS: All infants or
      neonates were swabbed on the day of admission and every third day thereafter and
      risk factors were collected for every day on the unit. RESULTS: During the study
      period, 245 neonates and 42 infants were sampled for their entire duration of
      stay on the unit. Of these, 41 infants (97.6%) were colonized with Malassezia on
      admission to the unit and thereafter, as assessed by subsequent samples. Within
      the neonate population, 78 (31.8%) became colonized, but none were colonized
      immediately after birth. Univariate analysis showed that many factors appeared to
      be significantly associated with colonization in the neonates, including use of
      ventilation, presence of central venous catheters, use of parenteral nutrition,
      and use of antibacterial or antifungal drugs. However, when the data were
      analyzed by multivariate logistic regression to control for confounding
      variables, only gestational age and length of stay on the unit were found to be
      significantly associated with colonization. CONCLUSION: Colonization of infants
      is not as unusual as previously thought and many infants have established a
      cutaneous Malassezia commensal flora by the age of 3 to 6 months. Factors that
      predispose to colonization in neonates may not be the same as those that
      predispose to infection.

PMID- 12002237
TI  - A comparison of the effect of early insertion of standard latex and silver
      impregnated latex foley catheters on urinary tract infections in burn patients.
AB  - A retrospective study was designed to compare the incidence of urinary tract
      infections during two different time periods in burn patients treated with two
      different types of Foley catheters. In time period 1, latex catheters present on
      admission were not changed. In time period 2, catheters were replaced on
      admission with silver alloy-impregnated catheters. In time period 1, the rate of
      symptomatic urinary tract infections was 7.2 per 1,000 catheter-days. In time
      period 2, the rate was 4.4 per 1,000 catheter-days. Results, compared using
      Fisher's exact test, revealed a statistically significant P value of .029. The
      use of silver-impregnated catheters significantly lowered the rate of urinary
      tract infection at our burn center.

PMID- 12002238
TI  - Occlusive scrub suits in operating theaters during cataract surgery: effect on
      airborne contamination.
AB  - The effect of wearing occlusive scrub suits on bacterial contamination of air was
      studied during cataract operations. All personnel regularly wore cotton scrub
      suits. During the intervention period, all wore occlusive scrub suits, which,
      compared with cotton scrub suits, were associated with more than a 50% reduction
      in the load of airborne bacteria during operations.

PMID- 12002239
TI  - Temporal trends in tuberculosis hospitalization rates before and after
      implementation of directly observed therapy: New York City, 1988-1995.
AB  - New York City hospitalization rates were analyzed to investigate whether
      tuberculosis (TB) hospitalizations declined after implementation of directly
      observed therapy (DOT) for TB. TB hospitalization rates mirrored incidence rates
      in pattern but not in magnitude. Rates have declined significantly following
      widespread implementation of DOT in 1993.

PMID- 12002240
TI  - The bowel prep conundrum.

PMID- 12002241
TI  - Youth mentoring in perspective: introduction to the special issue.

PMID- 12002242
TI  - Effectiveness of mentoring programs for youth: a meta-analytic review.
AB  - We used meta-analysis to review 55 evaluations of the effects of mentoring
      programs on youth. Overall, findings provide evidence of only a modest or small
      benefit of program participation for the average youth. Program effects are
      enhanced significantly, however, when greater numbers of both theory-based and
      empirically based "best practices" are utilized and when strong relationships are
      formed between mentors and youth. Youth from backgrounds of environmental risk
      and disadvantage appear most likely to benefit from participation in mentoring
      programs. Outcomes for youth at-risk due to personal vulnerabilities have varied
      substantially in relation to program characteristics, with a noteworthy potential
      evident for poorly implemented programs to actually have an adverse effect on
      such youth. Recommendations include greater adherence to guidelines for the
      design and implementation of effective mentoring programs as well as more in
      depth assessment of relationship and contextual factors in the evaluation of
      programs.

PMID- 12002243
TI  - The test of time: predictors and effects of duration in youth mentoring
      relationships.
AB  - The effects and predictors of duration in youth mentor relationships were
      examined. The study included 1,138 young, urban adolescents (Mean age 12.25), all
      of whom applied to Big Brothers Big Sisters programs. The adolescents were
      randomly assigned to either the treatment or control group, and administered
      questions at baseline and 18 months later Adolescents in relationships that
      lasted a year or longer reported the largest number of improvements, with
      progressively fewer effects emerging among youth who were in relationships that
      terminated earlier. Adolescents who were in relationships that terminated within
      a very short period of time reported decrements in several indicators of
      functioning. Older adolescents, as well as those who had been referred for
      services or had sustained emotional, sexual or physical abuse, were most likely
      to be in early terminating relationships, as were married volunteers aged 26-30
      and those with lower incomes. Several dyadic factors were also found to be
      related to earlier terminations, including race, gender, and relationship
      quality.

PMID- 12002244
TI  - Natural mentors and adolescent resiliency: a study with urban youth.
AB  - Natural mentors may play an important role in the lives of adolescents. We
      interviewed 770 adolescents from a large Midwestern city. Fifty-two percent
      reported having a natural mentor. Those with natural mentors were less likely to
      smoke marijuana or be involved in nonviolent delinquency, and had more positive
      attitudes toward school. Natural mentors had no apparent effect on anxiety or
      depression. Using the resiliency theory framework, natural mentors were found to
      have compensatory but not protective effects on problem behaviors, and both
      compensatory and protective effects on school attitudes. Direct and indirect
      (mediated) effects of natural mentors are explored for problem behaviors and
      school attitudes. The potential importance of natural mentors is supported, and
      implications for future research are considered.

PMID- 12002245
TI  - Naturally occurring mentoring in Japan and the United States: social roles and
      correlates.
AB  - Although the word "mentor"has traditionally been used to describe a relationship
      between an older adult and a younger person, recent work has extended its usage
      to relationships with peers and groups rather than with individuals and uncoupled
      the instrumental and affective qualities of the role. This paper examines (a) the
      extent to which adolescents' relationships with significant others in different
      social roles are characterized by mentoring and (b) the extent to which mentoring
      and other relationship functions covary. Adolescents' naturally occurring social
      relationships are explored in two very different contexts-Japan and the United
      States-that differ in the norms and patterning of social interactions. College
      students (N = 365) used questionnaires to describe the extent to which relations
      with significant others were characterized by mentoring. Results indicate
      striking similarity in the patterning of results in the two countries and support
      the traditional view of mentoring. Mentoring is most likely to occur in
      relationships with adults (especially parents), rather than with peers, and with
      same-gender, rather than other-gender associates. Mentoring by parents appears to
      covary with other aspects of positive relationships, but be more independent in
      relationships with unrelated adults or peers. Although more of the variability in
      experienced mentoring is attributed to differences between associates than to
      differences between adolescents in both the United States and Japan, this is
      especially true of the United States. Results suggest that although "classic"
      mentoring is most common in both countries, mentoring is somewhat less
      constrained by social role differences in Japan than is in the United States.

PMID- 12002246
TI  - Mentoring college-age women: a relational approach.
AB  - Despite the popularity of mentoring programs, the relational dimension of
      mentoring has not been elucidated. Traditional conceptions of mentoring may
      exclude factors that are particularly important for women and girls, thus
      limiting the efficacy of mentoring programs for female adolescents. We suggest
      that the presence of relational qualities in the mentoring relationship (e.g.,
      empathy, engagement, authenticity, and empowerment) strongly influences the
      success of mentoring in the lives of young women. In this study, we use a
      promising new measure of mentoring, the Relational Health Index - Mentor, to
      explore the impact of relational aspects of mentoring in female college students.
      We found that mentoring relationships high in relational qualities were
      associated with higher self-esteem and less loneliness

PMID- 12002247
TI  - Ties to influential adults among black and white adolescents: culture, social
      class, and family networks.
AB  - Although prior research suggests the importance of nonparental adults to
      adolescents, the ecological context of those relationships has received little
      attention. This study examined ties to influential adults among 122 adolescents
      who varied by race, family structure, and gender The strongest effects were for
      race. Blacks reported stronger ties than Whites to the maternal grandmother as
      well as more supportive interactions with adult males. While race differences in
      grandparental ties were robust across social class (SES), ties to an influential
      adult male became nonsignificant upon controlling for SES. African American girls
      from divorced families consistently reported the strongest ties. Discussion
      considers the role of culture versus SES in explaining race differences.
      Implications for mentoring interventions are proposed, with special attention to
      the role of actualizing latent ties to already existing network members.

PMID- 12002248
TI  - The nature of adolescents' relationships with their "very important" nonparental
      adults.
AB  - As part of a larger program of research on the nature of adolescents'
      relationships with very important nonparental adults (hereafter referred to as
      "VIPs"), a community sample of 243 eleventh graders (mean age = 16.6 years) was
      surveyed, and a subgroup of 55 adolescents and their VIPs were interviewed about
      the nature and quality of their relationships. Results showed that (a) adolescent
      VIP relationships were a normative component of adolescent development, not a
      result of problems in adolescents' lives; (b) adolescent-VIP relationships were
      generally of high quality (e.g., high support, low conflict, and high mutuality);
      (c) there were significant differences between kin and nonkin VIPs in terms of
      the duration of relationships and frequency of contact, but not in the quality of
      relationships; and (d) VIPs whom adolescents designated as extremely important
      were distinguished from other VIPs in terms of providing a higher level of social
      support and a higher frequency of contact. Theoretical and practical implications
      of these findings are discussed.

PMID- 12002249
TI  - Full circle.

PMID- 12002251
TI  - Racial, ethnic health disparities improve.

PMID- 12002250
TI  - Calming ambience is latest trend in office design.

PMID- 12002252
TI  - Solyman Brown, a giant of dentistry and its poet laureate.
AB  - Solyman Brown 1790-1876), widely hailed by his contemporary literary
      establishment as the poet laureate of dentistry," was one of the visionary
      individuals who put dentistry on a true foundation of professionalism. He was
      instrumental in the formation of the first dental journal, the first national
      dental society, and the first dental school. He is one of the true giants in the
      history of American dentistry. Solyman Brown's great-great-grandson was cleaning
      out his father's attic and found a trunk full of original material relating to
      his illustrious forebear. Among the wealth of material was a notebook kept by
      Solyman's daughter, Augusta. Selections from it give us a rare personal insight
      into the type of person this significant dental historical figure was, as well as
      the struggles he endured in his hard life.

PMID- 12002253
TI  - Simultaneous immediate placement and immediate loading of implants in the
      maxilla: a case presentation.
AB  - The standard three- to six-month healing time for implants is no longer an
      absolute. In selected cases, it is now possible to load the implants in fewer
      than two months; and, in some cases, immediate loading is possible. This article
      contains a case study showing that with careful patient selection, immediate
      loading appears to be an acceptable technique.

PMID- 12002254
TI  - Trend indicators: the vital signs of your practice.
AB  - Production in a dental practice can decrease for reasons that are not always
      apparent. However, regularly reviewing 10 basic dental practice statistics can
      identify problems and suggest solutions. This article reviews those trend
      indicators and describes how they can be used to maintain the health of a
      practice.

PMID- 12002256
TI  - Getting to the heart of the matter.

PMID- 12002255
TI  - Your recall program: is it as productive as it could be?
AB  - A good recall system can improve the efficiency of any dental office. The
      majority of patients do not respond to the standard reminder postcard used in the
      passive recall system. An active prebooking system is far more productive. This
      article will outline an effective recall program and include discussion of
      implementation, verbal skills, and patient reactivation.

PMID- 12002257
TI  - Pleiotropic effects of HMG-CoA reductase inhibitors.
AB  - HMG CoA reductase inhibitiors (statins) have been shown to be effective lipid
      lowering agents and are able to significantly reduce cardiovascular mortality and
      morbidity in patients at risk for cardiovascular disease. Recent clinical and
      experimental data suggest that the benefit of statins may extend beyond their
      hepatic effects on serum cholesterol levels. This review summarizes the current
      evidence and the molecular mechanisms of the direct effects of statins on plaque
      stability, inflammation, endothelial function, oxidative stress, thrombosis and
      stroke. Furthermore, recent data on the effects of statins on bone marrow, bone
      density and dementia are described. In summary, statins have emerged as a novel
      and powerful tool to study cardiovascular biology, including protein
      isoprenylation, small G protein function, leukocyte activity and endothelial
      progenitor cells. These pleiotropic properties of statins may have important
      clinical implications in addition to lowering serum cholesterol.

PMID- 12002258
TI  - Oncogenic ras induces premature senescence in endothelial cells: role of
      p21(Cip1/Waf1).
AB  - Recent studies have shown that the presence of tumor suppressors such as p53 or
      p16 account for the lack of transformation in primary cells. To investigate a
      potential role of active Ras in atherosclerosis, we infected bovine aortic
      endothelial cells with a replication-deficient, recombinant adenovirus containing
      the activated H-Ras61L gene. Ras overexpression led after 72 hours to G1- and
      G2/M-cell cycle arrest due to induction of p21(Cip1/Waf1). Treatment of Ras
      infected endothelial cells with 40 ng/ml TNF-alpha for 20 hours augmented
      apoptosis 8-fold in comparison to Ad-Con (control virus with empty expression
      cassette) infected cells (36.2% vs. 4.3%, p < 0.001), while Ras itself did not
      cause any cell death. Furthermore, more than 58% of Ras-infected cells stained
      positive for senescence-associated beta-galactosidase activity as opposed to 2%
      in control vector-infected cells (p < 0.001), strongly suggesting a senescent
      phenotype in the Ras-infected population. We found further features of senescence
      in Ras-transduced endothelial cells, such as growth arrest and the lack of AP-1
      serum inducibility. Finally, we evaluated the role of p21(Cip1/Waf1) in this
      process of senescence. Adenoviral overexpression of p21 led to growth arrest by
      induction of G1- and G2/M-cell cycle arrest. In addition, p21-overexpressing
      endothelial cells were highly sensitive for TNF-alpha induced-apoptosis.
      Surprisingly, senescence-associated beta-galactosidase activity was not apparant
      in p21-infected endothelial cells, suggesting further signaling events necessary
      for the senescent morphology of endothelial cells. Our results demonstrate a
      novel way to render primary endothelial cells senescent by overexpressing
      oncogenic Ras. Increased sensitivity of senescent endothelial cells for cytotoxic
      stimuli seemed to be due to Ras-induced upregulation of p21(Cip1/Waf1). Future
      studies have to investigate a potential role of Ras in human vascular biology.

PMID- 12002259
TI  - Paclitaxel and cyclosporine A show supra-additive antiproliferative effects on
      smooth muscle cells by activation of protein kinase C.
AB  - We intended to establish a pharmacologic concept of synergistic antiproliferative
      effects on smooth muscle cells (SMC) by using paclitaxel and cyclosporine A at
      clinically applicable doses. Coronary SMC were incubated with paclitaxel and
      cyclosporine A at concentrations of 10-20 nmol/L and 83-415 nmol/L, respectively.
      Antiproliferative effects were assessed by cell counts, [3H]thymidine
      incorporation and cell cycle analysis. In addition, apoptosis was studied by
      cytoplasmic histone-associated DNA fragments and in vitro protein kinase C
      activity (PKC) was determined by immunoassay. We found paclitaxel and
      cyclosporine A to exert a highly supra-additive antiproliferative effect on SMC
      with significant reductions of cell counts (p < 0.01) and [3H]thymidine
      incorporation (p < 0.05). SMC were found to be arrested at the G2/M transition.
      This antiproliferative effect was observed in the absence of DNA fragmentation
      above values obtained for single compound treatment, which had virtually no
      impact on cell proliferation. DNA fragmentation started to increase at a drug
      combination comprising paclitaxel at the higher dose of 20 nmol/L. Under the
      treatment with both paclitaxel and cyclosporine A, PKC activity showed a 1.8-fold
      increase (p < 0.05) compared with untreated controls. In conclusion, PKC mediates
      supra-additive antiproliferative effects of paclitaxel and cyclosporine A on SMC.
      The data demonstrate a highly efficient pharmacologic concept for the inhibition
      of SMC proliferation. Further studies are needed to test this concept under in
      vivo conditions for the prevention of restenosis or transplant vasculopathy by
      systemic application of cyclosporine A--when already applied for
      immunosuppressive purposes--and local delivery of paclitaxel.

PMID- 12002260
TI  - Local photodynamic therapy reduces tissue hyperplasia after stenting in an
      experimental restenosis model.
AB  - Local photodynamic therapy was used to prevent neointimal hyperplasia after
      stenting. Slotted tube stents were placed with 16 atmospheres in porcine femoral
      arteries with the external diameter to match the diameter at 10 atmospheres.
      Animals were randomly allocated to Group 1 (stenting only); or Group 2 with
      stenting, local drug delivery of a photosensitizer (5 mg Photofrin) and
      subsequent exposure to light (photodynamic therapy, 100 J). Fourteen days later,
      all vessels were excised, fixed and processed for histology. Tissue hyperplasia
      was observed after stenting in vessels from Group 1. In Group 2 with photodynamic
      therapy, the myoproliferative response was significantly reduced. Tissue
      hyperplasia after stenting was effectively suppressed by photodynamic therapy.

PMID- 12002261
TI  - Effects of calmodulin and okadaic acid on myofibrillar Ca2+ sensitivity in
      cardiac myocytes.
AB  - Whereas it has been established that the phosphorylation of 20 kD regulatory
      myosin light chain (MLC20) is a key regulator of contraction in smooth muscle,
      troponin complex has been thought to be that of myofibrillar Ca2+ sensitivity in
      cardiac muscle. To elucidate the role of the phosphorylation of cardiac
      regulatory myosin light chain (MLC2) in the regulation of cardiac muscle
      contraction, we observed effects of calmodulin and okadaic acid, a protein
      phosphatase inhibitor, on myofibrillar Ca2+ sensitivity as estimated by pCa50
      values obtained from pCa-tension relationships using beta-escin-skinned
      cardiomyocytes from Wistar rat hearts, in relation to changes in the
      phosphorylation of myofibrillar regulatory proteins. Whereas myofibrillar Ca2+
      sensitivity tended to be progressively decreased by repeated Ca2+-activation in
      the absence of calmodulin (pCa50; from 5.91 to 5.86, n = 5), calmodulin (2.5
      microM) significantly increased myofibrillar Ca2+ sensitivity (pCa50; from 5.92
      to 6.03, n = 5, p < 0.05). Okadaic acid over 3 microM enhanced Ca2+-activated
      force, which was inhibited by 50 microM trifluoperazine, a calmodulin antagonist.
      Okadaic acid (3 microM) significantly increased myofibrillar Ca2+ sensitivity
      (pCa50; from 5.96 to 6.11, n = 6, p < 0.05). Whereas the phosphorylation level of
      troponin I was not changed by 3 microM okadaic acid, that of MLC2 was
      significantly increased by the same dose of okadaic acid (from 12 to 31%, n = 4,
      p < 0.05). These results suggest that MLC2 phosphorylation plays a partial role
      in the regulation of myofibrillar Ca2+ sensitivity in cardiac muscle.

PMID- 12002262
TI  - The inotropic response of the isolated, perfused, working rat heart to
      norepinephrine is attenuated by inhibition of nitric oxide.
AB  - Experiments on isolated, perfused, working left ventricular (LV) hearts of 66
      female Wistar rats were done to examine whether nitric oxide (NO) influences the
      effects of norepinephrine (NE) on coronary flow as well as on contraction and
      relaxation. Functional parameters were monitored before and after application of
      NE at a concentration of 3 X 10(-8) M in the absence and presence of the nitric
      oxide synthase (NOS) inhibitor L-nitro-arginine (L-NA) at a concentration of 1 X
      10(-4) M and of the spontaneous NO donor sodium (Z)-1-(N,N-diethylamino) diazen-1
      ium-1,2-diolat (DEA/NO) at a concentration of 1 X 10(-7) M. In control
      experiments, heart rate was varied by electrical stimulation between 200 and 400
      beats/min. Within this range of heart rates, coronary flow and cardiac output
      remained constant, while stroke volume, LV peak pressure and LV dP/dt(max)
      decreased with increasing heart rate. NE increased coronary flow from 7.6 +/- 0.4
      to 9.8 +/- 0.7 ml/min and induced the well-known positive chronotropic and
      inotropic effects. DEA/NO increased coronary flow; however, the inotropic and
      lusitropic parameters were not affected. Simultaneous infusion of NE with DEA/NO
      further increased coronary flow from 9.8 +/- 0.7 to 12.1 +/- 0.8 ml/min without a
      significant effect on any other functional parameter. When NOS was inhibited by L
      NA, the positive inotropic effect of NE was attenuated. Cardiac output, however,
      was increased, while coronary flow did not change significantly. Under these
      conditions, NE increased dP/dt(max) by 65.5 +/- 5.8% (from 2999 +/- 97 to 4929 +/
      230 mmHg/s) compared with an increase by 92.8 +/- 6.7% (from 3770 +/- 82 to 7234
      +/- 211 mmHg/s) under control conditions. Application of DEA/NO reversed the
      attenuated inotropic response, but relaxation remained partially impaired. Thus,
      the presence of NO seems to be necessary for the inotropic effect of NE to become
      manifest.

PMID- 12002263
TI  - Persistence of neoangiogenesis and cardiomyocyte divisions in right ventricular
      myocardium of rats born and raised in hypoxic conditions.
AB  - Effects of chronic hypoxia on capillary and myocyte growth were examined in rats
      born and raised in a low pressure chamber (equivalent of 3500 m a.s.l.). The
      animals were sacrificed at the age of 3 months and their hearts were used to
      study right ventricular growth and vascularization. The results of our
      cytological and morphometric analysis suggest the persistence of capillary
      neogenesis in this particular model of cardiac hypertrophy. Under the optical
      microscope, we observed significant changes in capillary spatial patterns such as
      the presence of sinusoids and irregular capillary sprouts. This resulted in a
      significant shortening of the effective diffusion distance and in a slight
      decrease in the calculated diameter of the Krogh cylinder. Concomitant to the
      remodeling of the terminal capillary network, the right ventricular myocardium of
      hypoxic rats exhibited peculiar changes in myocyte cytology. The principal
      alteration consisted in the ectopic subsarcolemmal location of some of muscle
      cell nuclei which appeared enlarged and rounded, sometimes irregularly folded. At
      the E. M. level, they presented chromatine condensation, nucleolemmal folding
      and, occasionally, nuclear splitting. Irregular chromatin densifications at the
      equatorial position were also encountered but we never observed nucleolemmal
      dissolution or typical metaphase plaques which excludes the presence of mitotic
      division. Some of the marginalized nuclei were progressively excluded from
      original binucleate cells into small cytoplasmic processes that invaded the
      adjacent neo-formed pericapillar spaces and gave rise to small well-organized
      cardiomyocytes. This apparent fragmentation of cardiomyocytes may evoke the
      description of the apoptotic process which is believed to be stimulated in
      hypoxic tissues. However, we could not confirm that myocyte fragmentation that we
      describe is followed by shrinkage necrosis or by any mobilization of adjacent
      resident cells. Nuclear exclusions into pericapillary myocyte sprouts may,
      therefore, reflect amitotic divisions of polyploid cardiomyocytes which
      contribute to the persistence of hyperplasic growth in right ventricular
      myocardium in hearts of rats exposed to chronic hypoxia during their early
      postnatal life. Par analogie with our data, it can be expected that an
      appropriate stimulation of angiogenesis in hearts of adult animals attenuates
      some of cytological and functional drawbacks that accompany hypertrophic
      cardiomyopathies of other etiologies.

PMID- 12002264
TI  - Cardioprotective effects of chronic hypoxia and ischaemic preconditioning are not
      additive.
AB  - The objective of the work was to examine whether adaptation to intermittent high
      altitude hypoxia and ischaemic preconditioning provide additive protection of the
      heart against subsequent acute ischaemic injury. Adult male rats were exposed to
      hypoxia (7000 m, 8 h/day, 24-30 exposures) in a hypobaric chamber. Susceptibility
      of their hearts to ischaemia-induced ventricular arrhythmias and infarction was
      evaluated in open-chest animals subjected to 30-min coronary artery occlusion and
      4-h reperfusion. Preconditioning was induced by either two (PC1) or five (PC2)
      occlusions of the same artery for 5 min, each followed by 5-min reperfusion.
      Adaptation to hypoxia decreased the arrhythmia score from 2.75 +/- 0.13 in
      normoxic controls to 2.17 +/- 0.18. Both PC1 and PC2 reduced the arrhythmia score
      in the controls (0.15 +/- 0.10 and 0.71 +/- 0.24, respectively), as well as in
      the hypoxic groups (0.40 +/- 0.15 and 0.27 +/- 0.15, respectively). The infarct
      size was reduced from 66.6 +/- 2.3% of the area at risk in the controls to 50.2
      +/- 1.9% in the adapted rats. PC1 conferred further protection in adapted animals
      (38.4 +/- 2.8%) but this combined effect was of the same magnitude as that of
      preconditioning in the controls (37.5 +/- 1.6%). Similar results were obtained
      using PC2. It is concluded that adaptation to hypoxia decreases the efficiency of
      ischaemic preconditioning; cardioprotective effects of these two phenomena are
      not additive. The results are consistent with the view that the mechanisms of
      protection conferred by chronic hypoxia and preconditioning may share the same
      signalling pathway.

PMID- 12002265
TI  - Lactate-induced translocation of GLUT1 and GLUT4 is not mediated by the
      phosphatidyl-inositol-3-kinase pathway in the rat heart.
AB  - We have determined the effect of lactate on the translocation of GLUT1 and GLUT4
      and on the myocardial uptake and phosphorylation of the glucose analogues 2-deoxy
      D-glucose (DG) and 2-18F-fluoro-2-deoxy-D-glucose (18FDG). The involvement of
      phosphatidyl-inositol-3-kinase (PI3K) in this translocation was determined using
      wortmannin. Hearts from fed and fasted male Wistar rats were perfused in the
      presence of 11 mM glucose +/- 10 mM lactate for two hours and the distribution of
      glucose transporters was determined using Western blot techniques. Two other
      groups of hearts from fed animals were perfused in the presence of 11 mM glucose
      +/- 10 mM lactate for two hours followed by perfusion for a further 30 minutes in
      the presence of 4 mM 2-deoxy-D-glucose. Using 31P NMR spectroscopy, the
      accumulation of 2-deoxy-D-glucose-6-phosphate (DG6P) was monitored over time.
      Another group of hearts from fed animals was initially perfused in the presence
      of 11 mM glucose for 100 minutes and then the perfusate was changed to 11 mM
      glucose + 10 mM lactate for a further 120 minutes. Using PET, the accumulation of
      2-18F-fluoro-deoxy-D-glucose-6-phosphate (18FDG6P) was monitored throughout the
      whole protocol. Lactate induced the translocation of both GLUT1 and GLUT4 to the
      plasma membrane (from 67 +/- 1% to 82 +/- 2% and from 16 +/- 1% to 28 +/- 2%,
      respectively (P < 0.05)) in hearts from fed animals; similar translocations were
      observed in hearts from fasted animals. Wortmannin did not inhibit the
      translocation of either GLUT1 or GLUT4. Glucose transporter translocation was
      accompanied by a significant inhibition of DG6P accumulation (4.24 +/- 0.68 vs.
      1.50 +/- 0.38; P < 0.001) and a decrease in the rate of 18FDG6P accumulation. In
      conclusion, lactate causes translocation of GLUT1 and GLUT4 to the plasma
      membrane, via a non-PI3K-mediated pathway. Despite this externalisation of the
      GLUT transporters, a marked decrease in the accumulation of both DG6P and 18FDG6P
      was observed.

PMID- 12002266
TI  - Central hypercapnic chemoreflex modulation of renal sympathetic nerve activity in
      experimental heart failure.
AB  - Activation of the sympathetic nervous system plays an important role in the
      pathophysiology and progression of congestive heart failure (CHF). The precise
      mechanisms responsible for sympathetic activation in CHF are not yet clearly
      established. An altered central hypercapnic chemoreflex modulation of sympathetic
      nerve activity (SNA) might be an explanation. Therefore, the response of
      postganglionic renal SNA to elevation of CO2 concentration in the inspiratory air
      to 2, 4, and 6% was determined in anesthetized, artificially ventilated rats
      after denervation of peripheral baro- and chemoreceptors 2 weeks (group A; n=8)
      or 6 weeks (group B; n=11) after induction of an aorto-caval shunt, or 4 weeks
      after aortic banding (group C; n=7). In all CHF models, left ventricular
      enddiastolic pressure was increased (A 8 +/- 1, B 8 +/- 1, C 10 +/- 2 mmHg) as
      compared to sham operated controls (A 3 +/- 1, B 4 +/- 1, C 5 +/- 1 mmHg).
      Indicative of left ventricular hypertrophy and pulmonary congestion, wet weight
      of heart (A + 60%, B + 93%, C + 49%) and lungs (A + 15%, B + 36%, C + 12%) were
      also enhanced as compared to controls. Elevation of inspiratory CO2 concentration
      to 2,4, and 6% increased renal SNA by approximately 10, 20, and 30% from resting
      activity in all groups. The maximum SNA responses at 6% CO2 in the groups with
      CHF (A + 390 +/- 95, B + 425 +/- 133, C + 368 +/- 158 microVs) did not differ
      from those in the respective controls (A + 510 +/- 130, B + 570 +/- 180, C + 275
      +/- 25 microVs). It is concluded that under these experimental conditions the
      central hypercapnic chemoreflex sensitivity is not altered in either of the
      employed models of CHF and therefore may not play a major role for the well-known
      elevation of SNA in CHF.

PMID- 12002267
TI  - A bromine compound existing in blood.
AB  - Since a bromine compound with REM-sleep-inducing and anti-choline esterase
      activities have been isolated from human cerebrospinal fluid, and was identified
      as 1-methylheptyl gamma-bromoacetoacetate, the compound was chemically
      synthesized. It was found that this compound was composed with three forms, i.e.,
      a keto-form, an enol-form that changed gradually from keto-form by tautomerism,
      and a stable six-membered ring form (= cyclic r-Br) converted from enol form,
      when it was chemically synthesized. In addition, it was found that the six
      membered ring form of this bromine compound was present in the human blood.
      However, in this case, the keto-form and the enol-form were not detected. When
      14C-butyrate was injected to rats, it was incorporated into the bromine compound
      in the blood of the animal and the bromine compound formed was found to be
      present mainly as the six-membered ring form. From these results, the mechanism
      for the formation of bromine compounds in human and animal blood were deduced.

PMID- 12002268
TI  - Metacarpal bone mineral density, body mass index and lifestyle among
      postmenopausal Japanese women: relationship of body mass index, physical
      activity, calcium intake, alcohol and smoking to bone mineral density: the Hizen
      Oshima study.
AB  - The present study was designed to investigate the influence of modifiable risk
      factors (body weight and lifestyle) for bone loss on bone mineral density (BMD).
      We examined age-specific changes in metacarpal BMD, and its associations with
      body mass index and lifestyle among 532 community-dwelling postmenopausal
      Japanese women. Measurements of the second metacarpal BMD were obtained from the
      hand radiographs using computer-assisted radiographic absorptiometry. Body height
      and weight were measured, and body mass index (BMI) was calculated. Physical
      activity index was calculated using validated questionnaire. Daily calcium intake
      and amount of ingested alcohol were estimated by semiquantitative food frequency
      questionnaire. Current smoking status was obtained by questionnaire. Metacarpal
      BMD decreased significantly with increasing age. Simple correlation analysis
      indicated that metacarpal BMD correlated significantly with BMI and physical
      activity index. On the other hand, metacarpal BMD did not correlate with calcium
      intake and alcohol drinking. Metacarpal BMD in current smokers was not different
      from that in nonsmokers. Multiple regression analysis showed that increasing age
      was associated with decreased metacarpal BMD and greater BMI increased metacarpal
      BMD. However, physical activity, calcium intake, alcohol drinking and current
      smoking were not significant determinants of metacarpal BMD. Our findings suggest
      that maintenance of adequate body mass (prevention for leanness) is important for
      prevention of postmenopausal bone loss.

PMID- 12002269
TI  - Influence of aging on the carcinogen-induced protein kinase activity in rat liver
      cell nuclei.
AB  - A carcinogen-induced increase in a protein kinase activity was found in cell
      nuclei of rat liver. The enzyme was extracted from isolated nuclei with a
      hypotonic buffer, retained to an anion-exchange column, eluted with 0.15 M NaCl
      containing solution and to be measured for the activity with casein as the
      substrate, showing a nature of a casein kinase. The change in the activity during
      the course of aging was studied with 5-, 10-, and 50-week old Wistar male rats.
      The activity was highest in 5-week-old rat but decreased in 10- and 50-week-old
      animal. A hepatocarcinogen, thioacetamide, induced an increase in activity in 10
      week old rats but rather decreased in 5- and 50-week-old rats. Aging suppresses
      the activity of this unique enzyme. Thioacetamide abolishes this suppression
      resulting in an increase in the activity of the enzyme at a certain stage of
      aging.

PMID- 12002270
TI  - The influence of fluoride ingestion on urinary aluminum excretion in humans.
AB  - Fluoride (F) and aluminum (Al) are both ingested daily in water, foods, and
      pharmaceuticals. Owing to the strong chemical affinity between F and Al, these
      elements can interact in biological systems. The purpose of the present study was
      to investigate the influence of F ingestion on Al excretion in humans. Six
      healthy volunteers ingested 100 ml of distilled water at 6:00 a.m. on day 1
      (control period) and the same volume of sodium fluoride solution containing 5 mg
      of F at 6:00 a.m. on day 2 (test period). A schedule for meals and for blood and
      urine collection was followed for the two successive days. The concentration of F
      was measured with an F-electrode, and Al was determined by ion-pair RP-HPLC with
      its complexation with 8-quinolinol. The mean concentration of serum F peaked
      within 30 minutes after ingestion of F and rapidly decreased thereafter, reaching
      baseline 24 hours later. In control period, there was no increase of Al
      concentration in serum in 24 hours. In test period, Al concentration in serum did
      not increase significantly compared with those in control serum. Although some
      variation was observed among subjects, cumulative amounts of F and Al excreted in
      urine during the test period were significantly higher than those during the
      control period. The results suggest that absorbed F enhanced urinary Al excretion
      and that the Al in urine may be, at least in part, derived from endogenous
      tissues.

PMID- 12002271
TI  - Different sensitivities to alpha1 adrenoceptor blockade on periarterial
      sympathetic nerve-induced constriction by low and high frequencies in canine
      isolated splenic arteries.
AB  - The periarterial nerve electrical stimulation at 4 and 10 Hz induced a monophasic
      vasoconstriction of the canine splenic artery in a pulse number-related manner (1
      30 pulses). The responses at 4 Hz were not significantly affected by 0.1 microM
      prazosin, but abolished by 1 microM alpha, beta-methylene ATP. Prazosin (0.1
      microM) partially but significantly inhibited responses at 10 Hz, and the
      remaining responses were blocked by 1 microM alpha, beta-methylene ATP. It
      indicates that the monophasic vasoconstrictor response to short pulses of
      stimulation at a low frequency is mediated by P2X-receptors, whereas the response
      at a high frequency may be due to activation of not only P2X-receptors but also
      alpha1 adrenoceptors.

PMID- 12002272
TI  - Occupational therapy for accessory nerve palsy after radical neck dissection.
AB  - The subjects in this study were ten patients with accessory nerve palsy after
      radical neck dissection. All the primary diseases that accounted for radical neck
      dissection were malignant tumors located at the head or neck. Every patient
      received occupational therapy and underwent evaluations before and after the
      therapy. The data we collected included the existence of resting pain and motion
      pain, and the active and passive range of motion during shoulder flexion and
      abduction. The occupational therapy programs were not adequately effective for
      resting and motion pain, however, every patient gained independence for
      activities of daily living and housekeeping activities. The occupational therapy
      significantly improved the patient's shoulder elevation in all movements;
      although, the active abduction was always significantly poor compared with
      flexion. In the meantime, there were no significant differences between passive
      shoulder flexion and abduction at all times. We can therefore understand that the
      accessory nerve palsy especially affects active shoulder abduction induced by the
      trapezius paralysis. Occupational therapy is an effective treatment for the
      improvement of shoulder function, however, the occupational therapy has limited
      effectiveness for coping with the pain.

PMID- 12002273
TI  - Effect of phosphodiesterase inhibitors on nitric oxide production by glial cells.
AB  - Nitric oxide (NO) is considered to play a crucial role in the development of
      various pathological processes in the CNS, such as neuronal degeneration,
      inflammation and demyelination. In order to search for the agents which suppress
      NO production in the CNS, we examined the effects of one of the agents which
      elevate cyclic AMP production, phosphodiesterase inhibitors (PDEIs), on NO
      production by glial cells in vitro. All the types of PDEIs, from type I- to V
      specific and non-specific, suppressed the production of NO by mouse microglia and
      astrocytes stimulated with lipopolysaccharide, in a dose-dependent manner.
      Suppression of inducible NO synthase by PDEIs was confirmed by the expression of
      mRNA by RT-PCR. Although it required 10 microM or higher concentration to
      effectively suppress NO production in vitro, certain combinations of three
      different PDEIs synergistically suppressed NO production by astrocytes at 1
      microM which could be obtained in vivo at usual therapeutic doses. Similary,
      combinations of three PDEIs at 1 microM synergistically increased intracellular
      cAMP in astrocytes. The suppressive effects of PDEIs on NO production were
      abolished by addition of tumor necrosis factor alpha (TNFalpha). Thus, the main
      suppression mechanism of NO might be indirect through suppression of TNFalpha.
      Since some PDEIs are reported to pass through the blood-brain-barrier, the
      combination of three PDEIs may be worth trying in neurological diseases, such as
      multiple sclerosis, human immunodeficiency virus-related neurological diseases
      and other neurodegenerative disorders in which NO may play a crucial role.

PMID- 12002274
TI  - CXC chemokine receptor 1 (CXCR1) is expressed mainly by neutrophils in inflamed
      gut and stomach tissues.
AB  - CXC chemokine receptor 1 (CXCR1) is one of the important receptors for CXC
      chemokines with ELR motif, of which interleukin 8 (IL-8; CXCL8) is
      representative. To identify the cell type(s) of CXCR1-expressing cells in
      inflamed stomach and gut tissues, we performed immunoperoxidase method using pre
      fixed frozen sections. In chronic gastritis associated with Helicobacter pylori
      infection (7 cases), CXCR1 was positive in neutrophils (polymorphonuclear
      leucocytes) in the lamina propria near the neck region and those in pit abscess.
      In ulcerative colitis (6 cases) and Crohn's disease (5 cases), CXCR1 was
      sporadically expressed by neutrophils in the mucosa, and particularly CXCR1+
      neutrophils were abundantly distributed in inflammatory granulation tissue in
      ulcer base. Double staining confirmed co-localization of CXCR1 and neutrophil
      elastase. Neither CD3+ T lymphocytes nor CD68+ macrophages were positive for
      CXCR1. Immunoelectron microscopy confirmed the cell surface localization of
      CXCR1. Neutrophils protect the host from microbial pathogens. However, they also
      cause damages to host tissues in chronic inflammation. Therefore, our study
      underscores the importance of CXCR1 expression in inflammatory processes.

PMID- 12002275
TI  - Effects of novel phenoxazine compounds, 2-amino-4, 4a-dihydro-4alpha, 7-dimethyl
      3H-phenoxazine-3-one and 3-amino-1, 4alpha-dihydro-4alpha, 8-dimethyl-2H
      phenoxazine-2-one on proliferation of phytohemagglutinin- or anti-human IgM
      activated human peripheral blood mononuclear cells.
AB  - We examined the in vitro effects of 2-amino-4, 4alpha-dihydro-4alpha, 7-dimethyl
      3H-phenoxazine-3-one(Phx 1)and 3-amino-1, 4alpha-dihydro-4a, 8-dimethyl-2H
      phenoxazine-2-one (Phx 2) on the proliferation of phytohemagglutinin (PHA)- or
      anti-human IgM-activated human peripheral blood mononuclear cells (PBMC). Phx 1
      and Phx 2 inhibited the incorporation of 3H-thymidine of PHA-activated PBMC by as
      much as 75% and 40%, respectively, at a concentration of 40 microM. The
      inhibition was dependent on the dose of Phx 1 and Phx 2. These results strongly
      suggest that Phx 1 and Phx 2 inhibit proliferation of T cells, because PHA
      specifically activates the T cells among PBMC. On the other hand, when PBMC were
      activated by anti-human IgM, which specifically stimulates B cells, the
      incorporation of 3H-thymidine was rather increased in the presence of 15.8 microM
      Phx 1 or Phx 2. However, at a higher concentration of Phx 1 or Phx 2 (50 microM),
      the incorporation of 3H-thymidine was increased by Phx 1, but was inhibited by
      Phx 2. These results suggest different effects of Phx 1 and Phx 2 on
      proliferation of human T and B cells.

PMID- 12002276
TI  - Nucleotide alteration of retinoblastoma protein-interacting zinc finger gene,
      RIZ, in human leukemia.
AB  - The retinoblastoma protein-interacting zinc finger gene (RIZ) is a zinc-finger
      type DNA binding protein and is postulated as a member of the nuclear protein
      methyltransferase superfamily. RIZ gene encodes for two proteins, RIZ1 and RIZ2.
      While RIZ1 contains the N-terminal PR (PRDI-BF1 and RIZ homologous)-domain, RIZ2
      lacks it. RIZ1 is now considered as a tumor suppressor. We analyzed nucleotide
      alteration of RIZ gene in human leukemia. The results revealed a single
      nucleotide polymorphism (SNP), T1704 to A, near the conserved Rb-binding domain,
      leading to an amino acid change, Asp283 to Glu. Interestingly, 17 of 21 leukemia
      cell lines are homozygous for the T1704 allele whereas only 2 of 20 normal
      subjects are homozygous for the allele. In addition, one base pair deletion in
      the poly (A)9 tract in the coding region near the C-terminal zinc-fingers was
      identified, resulting in frameshift, in 1 out of 17 leukemia cell lines, but no
      mutation in samples from 15 patients with acute lymphoblastic leukemia (ALL) and
      6 patients with adult T cell leukemia (ATL). In the PR or SH3 (src homology 3)
      domain of the RIZ gene, no mutation was found. These findings suggest that RIZ
      may be a possible target of structural alteration leading to leukemia.

PMID- 12002277
TI  - A case of diabetes, deafness, cardiomyopathy, and central sleep apnea: novel
      mitochondrial DNA polymorphisms.
AB  - We describe a case of diabetes mellitus complicated by neurosensory hearing loss,
      cardiomyopathy, and sleep apnea syndrome. A 48-year-old man who was admitted for
      treatment of a lacerated tendon of the right shoulder was also found to require
      preoperative control of diabetes, a condition that had been diagnosed 4 years
      earlier. The family pedigree suggested maternal inheritance of diabetes. The
      patient also had neurosensory hearing loss and the central type of sleep apnea
      syndrome. His myocardium was hypertrophic and the ultrastructural analysis showed
      morphologically abnormal mitochondria. On the basis of the apparent
      characteristic manifestations, we speculated that he had a mitochondrial disease.
      To elucidate the responsible mutation of mitochondrial DNA, we sequenced the
      patient's entire mitochondrial DNA derived from blood leukocytes and found 40
      sequence variants. Three of those, 5466 A/G, 7912 G/A, and 10601 T/C, have not
      yet been reported. Nine of the 40 variants were accompanied by an amino acid
      replacement, including 5466 A/G. Although we could not determine the most
      significant mutation, the variants of mitochondrial DNA may have been associated
      with this patient's unusually variable clinical manifestations.

PMID- 12002278
TI  - Delayed recovery of effector memory CD4+ T cells by highly active antiretroviral
      therapy in a patient with HIV-1 infection.
AB  - Effector memory T cells, which are potentially important in the protection
      against various pathogens, have been shown to be CCR7 negative. We report a case
      with HIV-1 infection in whom the change in the cell numbers of the subsets of
      CD4+ T cells, including CCR7 negative memory CD4 + T cells, in peripheral blood
      was monitored for more than one year after the initiation of highly active
      antiretroviral therapy. Percentage of each subsets in lymphocytes was measured by
      triple staining on lymphocyte fraction in flow-cytometry. The numbers of total
      CD4+ T cell, naive T cells, and CCR7 positive memory T cells successfully
      increased within half a month after the initiation of the therapy. Instead, the
      recovery of the cell number in CCR7 negative memory T cells delayed, and
      continued to increase untill 10 months after the initiation of the therapy. It
      suggests the possibility of delay in recovery of immune systems after the
      initiation of the therapy in HIV-1-infected patients, despite the prompt recovery
      of total CD4 + T cells.

PMID- 12002279
TI  - The relation between serum selenium value and cancer in Miyagi, Japan: 5-year
      follow up study.
AB  - To determine the relation between serum selenium (Se) values and the development
      of cancer, we compared serum Se levels among cancer patients, non-cancer
      patients, and healthy adults. Serum Se values in cancer patients were examined
      with respect to primary cancer sites separately. We tracked non-cancer patients
      and healthy people for 5 years after serum collection to examine whether low Se
      status is a risk factor for cancer. The mean serum Se values in cancer patients
      were significantly lower than in non-cancer patients. This difference, however,
      failed to exist in women 50 years of age and less. In the examination of serum Se
      values with respect to organs with primary cancer, mean serum Se values for 6
      organs were significantly lower than those in non-cancer patients and healthy
      people. However, female breast cancer patients showed a higher value. During the
      5 year follow up, patients who developed cancer had lower values than that in
      subject who remained non-cancer and sex differences were absent. We were unable
      to rule out low Se status, as a possible risk factor for cancer, a result
      supported by our 5-year follow-up. In distribution of non-cancer patients
      classified by serum Se values, the proportion of patients with low serum Se
      values (80 ppb or less) was relatively high (12%). If low Se status increases the
      risk of cancer, low Se status as a risk factor for cancer should be considered
      even in Japan, where Se intake is sufficient.

PMID- 12002280
TI  - Effect of an industrial discharge on water quality and periphyton structure in a
      pampeam stream.
AB  - Seasonal sampling was carried out at four sites on a pampean stream that receives
      industrial effluent from two textile factories. To evaluate water quality,
      several physical and chemical parameters were examined and the periphyton growing
      on cattail (Typha latifolia L.) were analyzed. Water quality and periphyton
      structure differed significantly between sites upstream and downstream of the
      discharge. Differences in temperature and also in concentrations of phosphate,
      dissolved oxygen, and phaeopigment were detected. At the same time, changes in
      the dominant algae groups were observed. Downstream of the industrial discharge,
      the number of Bacillariophyta decreased, while species of Cianophyta and
      Euglenophyta were more abundant. This abundance correlated with increased
      phosphate and organic matter content and decreased oxygen concentration. Although
      this study did not detect a reduction in the number of species, similarity
      between stands decreased downstream of the industrial discharge. Changes in
      community structure were readily detected in this situation because the
      communities of the polluted and unpolluted zones were qualitatively different.
      Periphyton growing naturally on Typha latifolia is a useful indicator of the
      impact of waste waters on the biota and can also be used to evaluate water body
      recovery.

PMID- 12002281
TI  - Biomonitoring heavy metals in estuaries: a field comparison of two brown algae
      species inhabiting upper estuarine reaches.
AB  - Biomonitoring dissolved heavy metals within estuaries, particularly at their
      upper reaches, frequently has to rely on several biomonitors; rarely a single
      species thrives all along the salinity gradient. To properly do so, it must be
      established whether those biomonitors actually accumulate heavy metals alike. In
      this study, two brown seaweeds from the upper section of three NW Spain estuaries
      -the widely-known Fucus vesiculosus and the estuarine Fucus ceranoides--were
      compared as metal biomonitors. Both species were collected at five locations
      where they either coexist or live close to each other and their heavy metal
      content (Cu, Cr, Mn, Zn, Fe, Al) was measured. Analyses were appropriately
      replicated for each species x location combination to allow a statistically
      reliable detection of differences in bioaccumulation, with particular emphasis on
      the magnitude of interspecific differences. The lack of significant differences
      for Cu, Mn, and Zn contents in F. ceranoides and F. vesiculosus supports the
      feasibility of their joint use to monitor these metals along the estuaries.
      Conversely, F. ceranoides concentrated significantly higher levels of Cr, Fe, and
      Al than F. vesiculosus and hence combining data for both fucoids to monitor these
      elements seems impractical. The correlation of species differences together with
      a similar Al:Fe ratio in both weed tissue and sediment suggest that Cr, Fe, and
      Al tissue-burdens might be considerably biased by sediment retained on the
      surface of the weed. Parallel analyses of Al and/or Fe in seaweeds and sediments
      could serve to keep track of this interference and may help to combine data from
      both fucoids for monitoring elements like Cr.

PMID- 12002282
TI  - Economic valuation of health impacts of air pollution in Mumbai.
AB  - Air pollution leads to serious negative impacts on health. The physical evidence
      is compelling. An attempt has been made in this paper to establish dose-response
      relationship of Ambient Air Quality Index and human health, based on time spent
      by an individual in different microenvironments during one day. Economic
      valuation of morbidity and mortality has been attempted through lost salary
      approach. The results show that the avoidance cost is 29% of the total health
      damage cost.

PMID- 12002283
TI  - A modified toxicity testing method using tropical marine microalgae.
AB  - Toxicity testing of four heavy metals (Cd, Cu, Mn and As) using four species of
      tropical marine phytoplankton, Chaetoceros calcitrans, Isochrysis galbana,
      Tetraselmis tetrahele and Tetraselmis sp., was carried out in multiwell plates
      with test volumes of 2 mL and the results compared to those of standard, large
      volume, shake-flasks. IC50 values (concentrations of metals estimated to inhibit
      50% growth relative to the control) were determined after 96 hours based on
      automated O.D. readings measured in Elisa microplates by a Multiskan
      spectrophotometer. Good agreement was achieved between O.D. readings and cell
      counts indicating that this new method is a simple, economical, practical and
      rapid technique for toxicity testing, and provides good reproducibility of IC50
      values. Results of the toxicity tests indicate that Cu was the most toxic metal
      (average IC50 values ranging from 0.04 to 0.37 mg L(-1)), followed by Cd (0.06
      5.7 mg L(-1)), Mn (7.2-21.4 mg L(-1)) and As (33.9-319.3 mg L(-1)). Test species
      had different degrees of sensitivity to the metals tested, with I. galbana and C.
      calcitrans the most sensitive to Cu, Cd and Mn. Based on these findings it is
      recommended that the existing Malaysian Interim Standards for Marine Water
      Quality for Cd and Cu be reviewed.

PMID- 12002284
TI  - Transport, deposition and biodegradation of particle bound polycyclic aromatic
      hydrocarbons in a tidal basin of an industrial watershed.
AB  - Polycylic aromatic hydrocarbons (PAHs) are common contaminants in industrial
      watersheds. Their origin, transport and fate are important to scientists,
      environmental managers and citizens. The Philadelphia Naval Reserve Basin (RB) is
      a small semi-enclosed embayment near the confluence of the Schuylkill and
      Delaware Rivers in Pennsylvania (USA). We conducted a study at this site to
      determine the tidal flux of particles and particle-bound contaminants associated
      with the RB. Particle traps were placed at the mouth and inside the RB and in the
      Schuylkill and Delaware Rivers. There was net particle deposition into the RB,
      which was determined for three seasons. Spring and fall depositions were highest
      (1740 and 1230 kg of particles, respectively) while winter deposition was
      insignificant. PAH concentrations on settling particles indicated a net
      deposition of 12.7 g PAH in fall and 2.1 g PAH in spring over one tidal cycle.
      There was no significant PAH deposition in the winter. Biodegradation rates,
      calculated from 14C-labeled PAH substrate mineralization, could attenuate only
      about 0.25% of the PAH deposited during a tidal cycle in fall. However, in the
      spring, biodegradation could be responsible for degrading 50% of the settling
      PAHs. The RB appears to be a sink for PAHs in this watershed.

PMID- 12002285
TI  - Fluoride in groundwater in selected villages in Eritrea (North East Africa).
AB  - A study was undertaken to estimate fluoride content in the groundwater in certain
      parts of rural Eritrea. North-East Africa, along the River Anseba. Standard
      procedure was adopted for fluoride detection. Results indicate elevated
      concentration of fluoride in groundwater. The highest concentration was found to
      be 3.73 mg L(-1), well above the safety level for consumption. Geological basis
      for the high concentration of high fluoride has been established; it is presumed
      to be the pegmatite intrusion hosted by a granitic batholith. Extensive dental
      fluorosis has been observed in the population exposed to drinking water of high
      fluoride content.

PMID- 12002286
TI  - The use of invertebrates to detect small-scale habitat heterogeneity and its
      application to restoration practices.
AB  - Recent conceptual and technological solutions to biodiversity assessment allow
      large numbers of invertebrate specimens to be processed rapidly and provide
      researchers and practitioners with a unique tool for characterizing habitats. One
      application of these advances is the ability to detect and monitor small-scale
      habitat heterogeneity and so provide a measure of ecosystem restoration. This
      case study presents a test of the efficacy of using invertebrates to assess and
      monitor ecological restoration following bush regeneration. Eight contiguous
      habitat patches within a suburb of northern Sydney, Australia, were selected to
      represent areas that had undergone different bush regeneration techniques. A
      nearby and relatively undisturbed area of bushland was also sampled. A total of
      57,806 ground-active invertebrate specimens from 35 different orders were
      collected in pitfall traps. 1,246 ant (Formicidae) specimens were further sorted
      into 46 ant morphospecies from 20 genera. Analyses of the three taxonomic data
      sets, including two different data transformations, demonstrated that: (i)
      invertebrate communities successfully characterized different sites, providing a
      high degree of differentiation among sites; (ii) ordinations of the sites allowed
      visual assessment of the impact of each management technique on the habitat
      relative to undisturbed habitats; and (iii) characterization of sites could be
      achieved using abundance classes or binary counts of ant morphospecies,
      representing potential cost and time savings. The project duration was a total of
      three person weeks and cost less than US$3,000 (1999 prices) to complete.
      Measurement of invertebrate assemblages will provide a tool for both rapid
      assessment of management decisions and a means by which to implement adaptive
      management and restoration.

PMID- 12002287
TI  - Enteromorpha flexuosa (Wulfen) J. Agardh (Chlorophyta: Ulvales)--evaluation as an
      indicator of heavy metal contamination in a tropical estuary.
AB  - The use of bioindicators for contaminant monitoring is popular in all sectors of
      the environment but quite often bioindicators are utilised without rigorous
      evaluation of their viability as an indicator. We report field and laboratory
      investigations into the value of a commonly found macroalga, Enteromorpha
      flexuosa (Wulfen) J. Agardh (Chlorophyta: Ulvales) as an indicator of copper,
      zinc and lead contamination in a tropical estuary in Fiji. In the laboratory,
      metal content of E. flexuosa after 60 days of growth in seawater containing
      increasing concentrations of the metals showed almost perfect correlation with
      metal concentrations in water for all three metals, and concentration factors
      obtained were generally higher than values reported for other species of
      Enteromorpha. Performance in the field was evaluated by a one-year monitoring of
      metals in E. flexuosa, water and sediments from a contaminated estuary. Metal
      concentrations in water were always below detection limits and field
      concentration factors could not be determined but the concentration of lead in E.
      flexuosa showed a high correlation with the lead content of sediments. Lack of
      such correlation for copper and zinc in the field suggests that other
      environmental factors besides metal load in the physical environment could be
      controlling the bioaccumulation of these two metals. Whilst demonstrating E.
      flexuosa to be a viable bioindicator for lead, these results also highlight the
      need for proper assessment before an organism is considered for environmental
      monitoring.

PMID- 12002288
TI  - Associations between distance lags, groundwater velocities, and detection
      efficiencies in groundwater monitoring networks.
AB  - Effects of distance lags between landfills and monitoring wells on contaminant
      detection capability were quantified in several groundwater velocity settings.
      Detection efficiency calculations were made with and without imposing a time
      limit on contaminant travel. In general, longer distance lags yielded higher
      detection efficiencies. However, detection efficiencies decreased as monitoring
      wells approached a buffer zone boundary imposing a maximum permissible
      contaminant transport distance. Imposing a time limit on contaminant travel
      substantially reduced detection efficiency in low velocity settings, especially
      at longer distance lags. Time limits were less significant in high velocity
      settings where contaminants more quickly reached monitoring wells. Detection
      efficiencies also decreased as velocity increased, but decreases were minor once
      the velocity reached a threshold value.

PMID- 12002289
TI  - 2001 Presidential Address. Inception of the Society of Laparoendoscopic Surgeons.

PMID- 12002290
TI  - Comparison of immune preservation between CO2 pneumoperitoneum and gasless
      abdominal lift laparoscopy.
AB  - OBJECTIVE: Carbon dioxide (CO2) pneumoperitoneum has been implicated as a
      possible factor in early immune preservation in laparoscopic surgery. Although
      the current analysis was not adequate to clarify this issue, the aim of this
      study was to compare CO2 insufflation laparoscopic cholecystectomy to gasless
      abdominal wall lift laparoscopic cholecystectomy with respect to preservation of
      the immune system. METHOD: An analysis of the temporal immune responses was
      performed in 2 similar groups of patients (n = 50) who were divided randomly into
      the categories of gas or abdominal wall lift laparoscopic cholecystectomy. The
      patients were matched with respect to age, weight, and operation time. The immune
      parameters (serum white blood cell count, cortisol, erythrocyte sedimentation
      rate [ESR], tumor necrosis factor-alpha [TNF-alpha], interferon-y [INF-gamma],
      interleukin-6 [IL-6], interleukin-8 [IL-8]) were assessed at preoperative 24
      hours and at postoperative 24 and 72 hours for the 2 groups. During the
      operation, the levels of cytokines that were cultured in the peritoneal
      macrophages were also checked. RESULTS: The serum white blood cell count,
      cortisol, and ESR levels were not statistically different in either of the 2
      groups. Further, the serum TNF-alpha, INF-gamma, IL-6, and IL-8 levels in both
      groups were not significantly different from each other at preoperative 24 hours,
      and postoperative 24 and 72 hours. However, an immediate decrease in the cytokine
      levels at 24 hours after the operation was significant in both groups. The
      cytokine levels were particularly higher in the cultured peritoneal macrophages
      than in the serum, but were not statistically different between the 2 groups.
      CONCLUSION: Our results showed that the beneficial immune response obtained in
      the CO2 gas insufflation laparoscopic procedure could also be obtained in the
      gasless abdominal wall lift laparoscopic procedure. An immediate preservation of
      the immune functions in the postoperative period was detected similarly in the 2
      groups.

PMID- 12002291
TI  - Comparison of laparoscopic Burch and tension-free vaginal tape in treating stress
      urinary incontinence in obese patients.
AB  - OBJECTIVE: To compare the efficacy and safety of the tension-free vaginal tape
      (TVT) and laparoscopic Burch procedures in treating genuine stress urinary
      incontinence in obese patients. METHODS: This was a retrospective evaluation of
      91 consecutive cases of TVT alone or TVT combined with other procedures from
      April 1999 through March 2000 and 51 consecutive cases of the laparoscopic Burch
      procedure from January 1998 through February 1999. All procedures were performed
      in a private practice and community hospitals in the midwest. One hundred forty
      two women (ages 34 to 79) with stress urinary incontinence documented by clinical
      examination and preoperative cystometric and urodynamic evaluation were included
      in the study. They were also divided into 5 groups based on their body mass index
      (BMI): NL (normal-BMI < 25), OW (overweight-BMI 25 to 29), OBI (obesity I-BMI 30
      to 34), OBII (obesity II-BMI 35 to 39), OBIII (obesity III-BMI > 40). In the TVT
      group, 66% were obese (OBI-21, OBII-17. OBIII-22) versus 36% in the laparoscopic
      Burch (OBI-13, OBII-5) group. RESULTS: All TVT patients remain cured or symptoms
      improved in their genuine stress urinary incontinence, which favorably compares
      with the laparoscopic Burch procedure after 1 year. Operating time for the TVT
      portion ranged from 18 to 40 minutes. The laparoscopic Burch procedure in general
      took over 1 hour. No bladder, bowel, or vascular injuries have occurred in the
      TVT group. Superficial suprapubic ecchymoses have occurred in the TVT group
      occasionally but required no intervention. The average length of stay was 1 day;
      TVT-only patients usually were released on the same day. Ninety percent of
      patients were voiding normally by postoperative day 7. Most of the patients with
      continued urinary retention had had combined procedures. CONCLUSIONS: This
      preliminary study indicates that TVT is a safer, more effective, and easier
      minimally invasive surgery for genuine stress urinary incontinence regardless of
      the patients' BMI and favorably compares with the laparoscopic Burch procedure,
      which requires advanced surgical skills.

PMID- 12002292
TI  - Hysteroscopic endometrial destruction, optimum method for preoperative
      endometrial preparation: a prospective, randomized, multicenter evaluation.
AB  - OBJECTIVE: To compare the outcome and cost-effectiveness of various forms of
      preoperative endometrial preparation prior to hysteroscopic endometrial
      destruction for abnormal uterine bleeding. METHODS: This was a multicenter,
      prospective, comparative, randomized study conducted in a tertiary care hospital
      in Cairo, Egypt and 2 academic tertiary care teaching hospitals in the United
      States. One hundred thirty-one premenopausal women, who had completed
      childbearing, mean age of 45.7 years, with abnormal uterine bleeding refractory
      to medical management without histologic evidence of endometrial neoplasia were
      studied. The 131 patients were randomized for preoperative preparation for
      hysteroscopic endometrial destruction into 1 of 5 groups as follows: Group I,
      dilation and curettage (D & C) (39); Group II, gonadotropin-releasing hormone
      analogue (GnRHa) for 1 month (23); Group III, GnRHa for 3 months (26); Group IV,
      danazol for 3 months (26); and Group V, medroxyprogesterone acetate (MPA) 15 mg
      for 3 months (27). The choice of endometrial ablation or endometrial resection
      was left to the surgeon. RESULTS: Improvement in bleeding patterns, amenorrhea,
      operative times, complications, and relative cost were the measured outcomes. The
      mean follow-up time was 1 year from the time of the procedure. Overall, in Group
      I, 39/39 (100%) improved and 7/39 (18.0%) experienced amenorrhea; in Group II,
      21/23 (91.3%) improved and 9/23 (39.1%) experienced amenorrhea; in Group III,
      24/26 (92.3%) improved and 10/26 (38.5%) experienced amenorrhea; in Group IV,
      24/26 (92.3%) improved and 9/26 (34.6%) experienced amenorrhea; and in Group V,
      23/27 (85.1%) improved and 7/27 (25.9%) experienced amenorrhea. CONCLUSION:
      Endometrial destruction whether by the ablation or resection technique,
      regardless of the type of surgical pretreatment is a safe and effective surgical
      approach for treating abnormal uterine bleeding. D & C or MPA appear to be the
      most cost-effective pretreatment regimens. MPA pretreatment may confer the added
      advantage of decreasing blood flow and allowing better hysteroscopic
      visualization than D & C pretreatment.

PMID- 12002293
TI  - Perioperative management in children with sickle cell disease undergoing
      laparoscopic surgery.
AB  - OBJECTIVE: The aim of this study was to evaluate our experience with laparoscopic
      surgery in children with sickle cell disease. METHODS: A retrospective chart
      review was performed to analyze the indication for surgery, perioperative
      management, surgical technique, complications, duration of hospitalization, and
      outcome. One pediatric surgeon performed all procedures. RESULTS: Thirteen
      children underwent laparoscopic surgery for the following indications:
      symptomatic cholelithiasis/cholecystitis in 9; recurrent splenic sequestration in
      3; and hypersplenism/symptomatic cholelithiasis in 1. The 7 boys and 6 girls had
      a median age of 7.8 years. Patients undergoing splenectomy only were younger than
      those undergoing cholecystectomy (median age, 3.6 years versus 11.5 years,
      respectively). Four children underwent endoscopic retrograde
      cholangiopancreatography (ERCP) and sphincterotomy because of common bile duct
      dilatation and stones. Twelve patients received packed red blood cell
      transfusions prior to surgery. The median operative time was 150 minutes, and the
      median hospitalization was 3 days. Four patients suffered postoperative
      complications (2 with acute chest syndrome, 1 with recurrent abdominal pain, and
      1 with priapism). The patient with abdominal pain was found to have a retained
      stone in the common bile duct, which was retrieved via endoscopic retrograde
      cholangiopancreatography and sphincterotomy. All complications resolved with
      medical management. CONCLUSIONS: Laparoscopic surgery is safe in children with
      sickle cell disease. Meticulous attention to perioperative management,
      transfusion guidelines, and pulmonary care may decrease the incidence of acute
      chest syndrome.

PMID- 12002294
TI  - Causes of long-term dysphagia after laparoscopic Nissen fundoplication.
AB  - BACKGROUND: Laparoscopic fundoplication has revolutionized the surgical treatment
      of gastroesophageal reflux disease. Despite improvements in the technique of
      fundoplication, persistent dysphagia remains a significant cause of postoperative
      morbidity. METHOD: Causes of persistent postoperative dysphagia were analyzed in
      a consecutive series of 167 patients after laparoscopic Nissen fundoplication.
      Short gastric vessel division and its effect on postoperative dysphagia were
      analyzed. RESULTS: Follow-up was possible in 139 patients (83%). The mean follow
      up period was 27 +/- 21 months. Nine patients (6%) had persistent (moderate to
      severe) dysphagia, and 33 patients (24%) had mild dysphagia. The satisfaction
      score among patients with persistent dysphagia was significantly lower than that
      in patients with mild dysphagia (P < 0.0002). On the other hand, the satisfaction
      rate among patients with mild dysphagia and those who are asymptomatic was
      similar. Manometry, performed in 7 of 9 persistent dysphagia patients revealed no
      difference in postoperative lower esophagus sphincter (LES) pressure and
      relaxation as compared with that in the control group (n = 52). Six of 9 patients
      with persistent dysphagia underwent a re-do antireflux procedure. Dysphagia as
      related to fundic mobilization (complete vs. partial) or bougie size (< 58 Fr.
      vs. > or = 58 Fr.) revealed no difference in the dysphagia ratings. CONCLUSIONS:
      Laparoscopic short Nissen fundoplication with or without fundic mobilization
      achieved an acceptable long-term dysphagia rate. Careful patient selection,
      identification of the short esophagus, and accurate construction of the
      fundoplication can lead to a decrease in the incidence of persistent
      postoperative dysphagia.

PMID- 12002295
TI  - The "learning curve" in videoscopic Heller myotomy.
AB  - OBJECTIVES: In the early 1990s, minimally invasive videoscopy was applied to
      numerous operations. After undertaking more than 50 "open" Heller myotomies, our
      experience with videoscopic Heller myotomy began in 1992. We sought to determine
      whether the outcome following videoscopic Heller myotomy is influenced by surgeon
      experience. METHODS: Seventy-eight patients with severe dysphagia secondary to
      achalasia underwent videoscopic Heller myotomy between 1992 and 1998.
      Intraoperative endoscopy was utilized to ensure adequate myotomy in all patients.
      Patients were stratified into 3 groups: the first 25 patients (group I), the
      second 25 patients (group II), and the last 28 patients (group III). Clinical
      outcome was based on length of stay, incidence of intraoperative complications,
      conversion to an 'open' procedure, and postoperative symptoms. RESULTS:
      Perioperative complications occurred in 20% of patients in group I compared with
      8% and 12% in groups II and III, respectively (P = NS). Only 3 patients required
      conversion to an 'open' procedure, all in group I (P <0 .05). Symptomatic
      improvement was achieved in 80% of patients in group I, 100% in group II, and 96%
      in group III (P < 0.05). Significant reductions in conversions to open, length of
      stay, and postoperative symptoms were seen after 20 myotomies were undertaken.
      CONCLUSION: Outcome following videoscopic Heller myotomy, like other videoscopic
      operations, improves as surgeons progress along the videoscopic "learning curve."
      After approximately 20 videoscopic Heller myotomies, surgeons can expect fewer
      conversions to open procedures, shorter hospital stays, and better symptomatic
      relief.

PMID- 12002296
TI  - The implications of lighted ureteral stenting in laparoscopic colectomy.
AB  - OBJECTIVE: The placement of indwelling ureteral catheters during colorectal
      surgery has been recommended for prevention of ureteral injuries. With the advent
      of laparoscopic colectomy (LCo), the role of preoperative placement of lighted
      ureteral stents (LUS) has also become commonplace. We sought to evaluate the
      value of lighted ureteral stent placement in laparoscopic colectomy. METHODS:
      Sixty-six patients underwent LCo with LUS inserted preoperatively. Stents were
      removed in the immediate postoperative period. Two surgeons performed all the
      colectomies; 32 patients were males and 34 were females. Fifty patients underwent
      sigmoid colectomy, 4 had abdominoperineal resection, 4 had right colectomy, and 1
      each had transverse or subtotal colectomy. Eighteen patients had a diagnosis of
      cancer, 34 had diverticular disease, and 14 had neoplastic polyps. Forty patients
      had bilateral and 26 had unilateral stent placement. A review of the incidence of
      ureteral injuries, hematuria, and anuria as the cause of acute renal failure was
      accomplished, comparing the unilateral and bilateral stented groups. RESULTS: One
      (1.5%) patient suffered a left ureteral laceration during sigmoid colectomy. This
      was managed successfully with stent reinsertion. Sixty-five (98.4%) patients had
      gross hematuria lasting 2.93 days (1 to 6 days). The cost of bilateral stent
      placement was $1,504.32. A statistically significant difference occurred in the
      duration of hematuria (days) between patients who had unilateral (2.5 +/- 0.82)
      and bilateral stent placement (3.37 +/- 1.05), (P < 0.001). Four patients
      suffered from anuria, 2 required renal support needing hemodialysis for 3 to 6
      days, 3 (75%) had bilateral stents, and 1 (25%) had a unilateral stent.
      CONCLUSIONS: We recommend the placement of lighted ureteral stents as a valuable
      adjunct to laparoscopic colectomy to safeguard ureteral integrity. Transient
      hematuria is common but requires no intervention. Reflux anuria occurs
      infrequently and is reversible.

PMID- 12002297
TI  - Nitric oxide expression by interleukin-10 in the endoscopic and open methods of
      vein harvesting in coronary artery bypass surgery.
AB  - OBJECTIVE: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that
      suppresses lymphocyte functions, regulates production of proinflammatory
      cytokines, and suppresses nitric oxide production by activated macrophages. We
      examined IL-10 expression and its value as a surrogate index for nitric oxide
      (NO) production in endothelial cultures obtained from saphenous vein samples.
      METHODS: Using 2 different techniques (the open and endoscopic), we harvested
      samples of human saphenous veins from 90 randomly selected patients undergoing
      coronary artery bypass surgery (CABG). Endothelial cells collected from the vein
      samples retrieved through both techniques were cultured for 72 hours. Using a
      solid phase enzyme linked-immuno-sorbent assay (ELISA), we analyzed pre- and
      postoperative sera, in addition to the supernatants from the cultures, for IL-10.
      RESULTS: Mean preoperative levels of IL-10 (0.09 +/- 0.04 pg/mL) did not differ
      significantly from that for postoperative sera (0.14 +/- 0.17 pg/mL) (P = 0.54).
      Mean IL-10 levels for endothelial cell culture supernatants did not differ
      significantly between the endoscopic (0.32 +/- 0.39 pg/mL) and the open method
      (0.46 +/- 0.80 pg/mL) (P= 0.30). CONCLUSION: Our findings indicate that
      endoscopic and open saphenectomies are technically comparable with respect to
      their effects on IL-10 release during saphenous vein harvesting for CABG. We
      recommend the endoscopic method for its low morbidity and earlier hospital
      discharge.

PMID- 12002298
TI  - Hydro-Jet assisted laparroscopic cholecystectomy: initial experience in a porcine
      model.
AB  - BACKGROUND AND OBJECTIVES: Hydro-Jet technology has long been used for cutting
      various materials like metal and wood in the industrial field. In the medical
      field, this technology has been applied successfully for selective cutting of the
      parenchyma of the liver. However, to our knowledge, no data exist on the use of
      the Hydro-Jet technique for laparoscopic cholecystectomy. The purpose of this
      study was to evaluate a new dissection technique using a high-pressure water
      stream (Hydro-Jet) and a new dissection probe for laparoscopic cholecystectomy.
      METHODS: Thirty pigs underwent laparoscopic cholecystectomy. Pigs were randomized
      to receive either the conventional or Hydro-Jet assisted dissection technique.
      The feasibility of this technique and the features of surgical dissection were
      evaluated and compared between the 2 groups. RESULTS: Laparoscopic
      cholecystectomy was successful in all animals with no need for conversion to open
      surgery. The mean operative time was 28 and 36 minutes for Hydro-Jet versus
      conventional dissection, respectively. Complications using the Hydro-Jet and
      conventional techniques included 6% and 20% gallbladder perforation and 6.5% and
      13% liver laceration, respectively. The use of the Hydro-Jet for cholecystectomy
      had clear technical advantages over conventional dissection. The Hydro-Jet
      resulted in a selective dissection of fibrous and connective tissue preserving
      blood vessels for later ligation. Therefore, the dissection was performed in a
      relatively bloodless field. The ease of dissection using the new bent tipped
      dissector represents another advantage. Finally, the continuous water flow
      allowed a clear view for the operator. CONCLUSIONS: This study shows that Hydro
      jet dissection represents an excellent alternative to the conventional technique
      for laparoscopic cholecystectomy. The improved anatomical dissection combined
      with an almost bloodless operating field secondary to continuous water flow may
      decrease dissection-related complications.

PMID- 12002299
TI  - A difficult laparoscopic cholecystectomy that requires conversion to open
      procedure can be predicted by preoperative ultrasonography.
AB  - A prospective study was conducted from March 1999 to April 2000 that included 73
      patients who underwent elective laparoscopic cholecystectomy for uncomplicated
      gallstone disease. The study was conducted at one surgical unit in the Department
      of Surgery and Department of Radio-diagnosis and one surgical unit in the
      Department of Surgery, Maulana Azad Medical College and the associated Lok Nayak
      Hospital, which is the largest referral hospital in northern India and is located
      in the capital of India. A preoperative ultrasound was performed just prior to
      surgery, and 4 ultrasonographic parameters were analyzed. namely gallbladder wall
      thickness, contracted gallbladder, impaction of gallstones at the neck of the
      gallbladder, and common bile duct stones. The surgical findings were objectively
      graded as difficult or easy laparoscopic cholecystectomy according to 5 operative
      parameters, namely total time taken for the surgery, time taken to dissect
      gallbladder bed, spillage of stones, tear of gallbladder during dissection, and
      conversion to the open procedure. Of the 73 cases, 17 (23.3%) were conversions to
      the open procedure. Of the 21 (28.76%) cases predicted to be difficult, 17
      (23.3%) were technically difficult, of which 13 (17.8%) were converted to the
      open procedure. Of the 52 (71.23%) cases predicted to be easy on ultrasonography,
      only 7 (9.38%) were found to be difficult on surgery, of which only 4 (5.48%) had
      to be converted to the open procedure. Based on our results, we conclude that
      preoperative ultrasonography is of great value in selecting patients
      preoperatively for laparoscopic cholecystectomy and minimizing complications and
      conversion to the open procedure.

PMID- 12002300
TI  - Acute cholecystitis and laparoscopic cholecystectomy.
AB  - OBJECTIVE: To determine whether laparoscopic cholecystectomy (LC) should be the
      procedure of choice in treating acute cholecystitis. METHOD: A prospective study
      was conducted over a 4 1/2-year period. There were 187 patients with acute
      cholecystitis out of 1020 patients with gallbladder disease who required
      cholecystectomy. These patients were divided into three groups based on the time
      interval between the onset of pain and the time patients sought medical
      attention: Group 1, < 3 days; Group 2, 3 to 7 days; Group 3, > 7 days. All the
      patients underwent LC after a comprehensive preoperative workup. The parameters
      analyzed included operating time, hospital stay, and conversion rate. The
      comparison was made among the various groups and with those who had elective LC.
      RESULTS: One hundred twenty patients (64.17%) presented for treatment within 3 to
      7 days of the onset of an attack. Empyema of the gallbladder was seen in 106
      (56.68%) patients and phlegmon of the gallbladder in 42 (22.46%) patients. Group
      3 patients had an operative time of 56.2 min as opposed to 18.5 min in Group 1
      and 17.5 min in the elective LC group. The conversion rate in Group 3 was 19.5%
      versus 3.8% in Group 1 and 3.48% in the elective LC group. The complication rate
      was 7.3% in Group 3, 3.8% in Group 1, and 3.7% in the elective LC group.
      CONCLUSION: Acute cholecystitis is better managed by laparoscopic
      cholecystectomy, except in the patients presenting with a gallbladder phlegmon
      later than 7 days after the onset of the attack.

PMID- 12002301
TI  - The laparoscopic-ring simulation trainer.
AB  - Regardless of the level of experience, surgeons need convenient times and
      locations to practice laparoscopic skills. Although attendance at formal courses
      is essential for continuing surgical education, reinforcement is still needed by
      other means to allow surgeons to learn new operations as they advance. A method
      is presented here that allows surgeons to practice laparoscopic skills while
      following their own time schedules. Novice surgeons can also benefit from this
      method by practicing basic laparoscopic skills in a cost-effective simulated
      operative environment. The Borinquen Ring pelvic trainer was originally described
      in 1993. It is now reintroduced along with an additional device called a Tissue
      Suspender to create a new laparoscopic simulation training system. Instruction is
      provided for the use of these 2 devices in practicing basic surgical skills.
      Different simulation models are used to substitute for human organs and vessels.
      These consist of both artificial and animal tissue specimens.

PMID- 12002302
TI  - Small bowel volvulus resulting in infarction due to an anterior gastropexy band.
AB  - Volvulus of the small bowel, although rare, carries a high risk of strangulation
      and ischemic necrosis. It is usually caused by the rotation of a loop of small
      intestine around an adhesion band or stoma. We present a case of an anterior
      gastropexy band, giving rise to a small bowel volvulus, necessitating resection
      due to infarction. This band resulted from separation of the most distal anterior
      gastropexy suture from the anterior abdominal wall. The distensible nature of the
      stomach and its resultant postprandial gain in weight produced tremendous
      shearing forces on the gastropexy sutures, and, as our case demonstrates, a
      greater number of gastropexy sutures does not protect against this complication.

PMID- 12002303
TI  - Laparoscopic management of abdominopelvic abscesses in tropical pyomyositis.
AB  - Tropical pyomyositis is a suppurative infectious disease of skeletal muscles. The
      most common causative organism is Staphylococcus aureus. Penicillin-resistant
      strains are frequently encountered. Abscesses may develop in muscle groups or
      body cavities remotely located from one another. We report a case of tropical
      pyomyositis presenting as a suppurative process in the left foreleg. Further
      workup, including CT scanning, demonstrated large, multi-loculated intraabdominal
      and pelvic abscesses. The abdominal and pelvic components were managed by
      laparoscopic exploration and drainage. This is the first known report of
      laparoscopic management of abdominopelvic abscesses associated with tropical
      pyomyositis.

PMID- 12002304
TI  - Re: Laparoscopic-assisted vaginal myomectomy: a case report and literature
      review.

PMID- 12002305
TI  - Re: Current concepts of pelvic congestion and chronic pelvic pain.

PMID- 12002306
TI  - Genetic effects on fatty acid composition of carcass fat of Japanese Black Wagyu
      steers.
AB  - Two hundred ninety-three Japanese Black Wagyu steers derived from 34 sires were
      used to investigate genetic effects on the fatty acid composition of carcass fat.
      All steers were fed identical diets for 365 d and slaughtered at similar ages. If
      the percentage of genetic contribution of sire A, B, or C was not lower than 25%,
      steers were classified into groups A, B, and C, respectively. Fatty acid
      compositions differed depending on deposit sites. Mean percentage of
      monounsaturated fatty acids (MUFA) tended to be higher in the outer parts than in
      the inner parts of the body. Percentage of MUFA in carcass fat was negatively
      correlated with withers height and BW and positively correlated with meat quality
      score and marbling score. Fatty acid compositions of the 34 sire groups varied,
      and mean percentages of MUFA in i.m. fat ranged from 47.71 to 54.77%. Steers in
      the C group grew larger than those in the A or B group. Mean percentages of MUFA
      for i.m. fat in the A, B, and C groups (52.83, 51.88, and 50.33%, respectively)
      differed (P < 0.05) from each other. Steers in the C group had higher (P < 0.05)
      percentages of saturated fatty acids than those in the A or B groups. Percentages
      of genetic contribution of sires B (P < 0.05) and C (P < 0.001) were negatively
      correlated with percentage of MUFA in i.m. fat. These results suggested that
      genetic factors affected fatty acid composition of carcass fat in Japanese Black
      Wagyu cattle and that some sires had potent genetic factors affecting this
      composition.

PMID- 12002307
TI  - Effects of beta-mannanase addition to corn-soybean meal diets on growth
      performance, carcass traits, and nutrient digestibility of weanling and growing
      finishing pigs.
AB  - Four experiments were conducted to determine the effects of adding a beta
      mannanase preparation (Hemicell, ChemGen, Gaithersburg, MD) to corn-soybean meal
      based diets on growth performance and nutrient digestibility of weanling and
      growing-finishing pigs. In Exp. 1, 156 weanling pigs (20 d, 6.27 kg BW) were
      allotted to four dietary treatments in a randomized complete block design.
      Treatments were a factorial arrangement of diet complexity (complex vs simple)
      and addition of 3-mannanase preparation (0 vs 0.05%). Pigs were fed in three
      dietary phases (Phase 1, d 0 to 14; Phase 2, d 14 to 28; and Phase 3, d 28 to
      42). Pigs fed complex diets gained faster and were more efficient (P < 0.05)
      during Phase 1 compared with pigs fed simple diets. Overall, gain:feed ratio
      (G:F) tended to be improved (P < 0.10) for pigs fed complex diets and it was
      improved (P < 0.01) for those fed diets with beta-mannanase. In Exp. 2, 117 pigs
      (44 d, 13.62 kg BW) were allotted randomly to three dietary treatments. Dietary
      treatments were 1) a corn-soybean meal-based control, 2) the control diet with
      soybean oil added to increase metabolizable energy (ME) by 100 kcal/kg, and 3)
      the control diet with 0.05% beta-mannanase preparation. Beta-mannanase or soybean
      oil improved (P < 0.05) G:F compared with pigs fed the control diet. In Exp. 3,
      60 pigs (22.5 kg BW) were allotted randomly to the three dietary treatments used
      in Exp. 2. Dietary treatments were fed in three phases (23 to 53 kg, 53 to 82 kg,
      and 82 to 109 kg with 0.95, 0.80, and 0.65% lysine, respectively). Overall, the
      addition of soybean oil tended to improve G:F (P < 0.10) compared with that of
      pigs fed the control diet, and G:F was similar (P > 0.54) for pigs fed diets with
      soybean oil or beta-mannanase. Also, addition of beta-mannanase increased ADG (P
      < 0.05) compared with that of pigs fed the control or soybean oil diets. There
      were no differences (P > or = 0.10) in longissimus muscle area or backfat;
      however, on a fat-free basis, pigs fed the diet with beta-mannanase had greater
      (P < 0.05) lean gain than pigs fed the control or soybean oil diets. In Exp. 4,
      12 barrows (93 kg BW) were allotted randomly to one of the three dietary
      treatments used in Exp. 3. Addition of 3-mannanase had no effect (P > 0.10) on
      energy, nitrogen, phosphorus, or dry matter digestibility. These results suggest
      that beta-mannanase may improve growth performance in weanling and growing
      finishing pigs but has minimal effects on nutrient digestibility.

PMID- 12002308
TI  - Influence of dietary conjugated linoleic acid on growth, meat quality,
      lipogenesis, plasma leptin and physiological variables of lipid metabolism in
      rabbits.
AB  - We investigated the effects of conjugated linoleic acid (CLA) supplementation on
      growth, feed efficiency, carcass characteristics, meat quality, lipogenesis, and
      lipid metabolism in rabbits. One hundred forty-four New Zealand White rabbits,
      half males, half females, age 55 d, mean 1.8 kg BW, were randomly assigned to
      three weight- and sex-balanced feeding groups in which conventional pelleted
      diets were supplemented with 0, 0.25, or 0.5% of a CLA preparation. The CLA
      preparation contained 65% CLA isomers. Twelve rabbits (six males and six females
      from each group) were slaughtered at each of three slaughtering trials (2.5, 2.8,
      and 3.1 kg BW, or 76, 90, and 104 d of age). Conjugated linoleic acid
      supplementation did not influence growth performance (P > or = 0.05) or carcass
      characteristics but reduced perirenal fat at heavier slaughtering weights (P =
      0.09 at 2.8 kg BW; P < 0.01 at 3.1 kg BW). Conjugated linoleic acid reduced
      acetyl-CoA-carboxylase (CBX) activity in liver (P < 0.05) and adipose tissues (P
      < 0.01) but did not influence malic enzyme (ME) or glucose-6-phosphate
      dehydrogenase activity. Significant differences were found between sex in
      interscapular fat (P < 0.05) for CBX, in perirenal (P < 0.01) and interscapular
      (P < 0.05) fat for ME, and a tendency (P = 0.070) in liver for glucose-6
      phosphate dehydrogenase. The oxidative stability of longissimus lumborum muscle
      was increased at the higher level of supplementation (P < 0.05). Conjugated
      linoleic acid reduced (P < 0.05) triglycerides and total cholesterol in plasma
      with a trend to increased serum leptin (P = 0.06). Plasma triglycerides were
      higher in males than females (P < 0.01) and plasma leptin tended to be higher in
      females (2.57 vs. 2.13 ng/ml, P = 0.06). It is concluded that dietary CLA reduced
      carcass fat in rabbits slaughtered at 2.8 kg or above and altered lipid
      metabolism to produce lower concentrations of serum triglycerides and total
      cholesterol and higher concentrations of leptin.

PMID- 12002309
TI  - Effect of levels of starch, fiber, and lactose on digestion and growth
      performance of early-weaned rabbits.
AB  - The effect of source of carbohydrate on gut histology, digestion efficiency, and
      growth performance in early-weaned (25 d) rabbits at the starter period (25 to 39
      d) was investigated. Six diets were factorially arranged to study the effect of
      partial substitution of starch (0, 25, or 50%) by lactose at two levels of fiber
      (30 or 36% NDF). Diets were formulated to meet or exceed essential nutrient
      requirements of growing rabbits. A feeding trial was conducted to measure the
      effect of treatments on growth performance in 252 rabbits that were fed the
      experimental diets in the starter period and thereafter received a common feed
      until 60 d of age. Fecal apparent digestibility was determined at 35 d of age in
      nine animals per diet. The four diets with extreme lactose content were used to
      determine ileal apparent digestibility of starch and lactose (nine replicates per
      diet), weights of stomach and cecum, stomach pH, cecal fermentation traits,
      amylase and disaccharidase activities (10 animals per diet), and jejunal
      morphology (six animals per diet). Weaning increased (P < 0.001) amylase activity
      by 59% but decreased (P < 0.001) maltase, sucrase, and lactase activities by 30,
      48, and 72%, in parallel with a reduction of villus height by 19%. Dietary NDF
      level did not affect either jejunal morphology or sucrase and lactase activities
      but increased amylase (P = 0.05) and maltase (P < 0.001) activities by 22 and
      92%, respectively. Substitution of starch by lactose had no effect on jejunal
      morphology or enzymatic activity. Ileal lactose and starch digestibility were not
      affected by dietary NDF or lactose level and averaged 73.8 and 90.8%,
      respectively. Substitution of starch by fiber and lactose affected ileal flux of
      starch plus lactose (by -0.5 and +1.7 g/d) and cecal pH (by +2.1 and -2.8%,
      respectively). Fecal NDF digestibility was relatively low (23.1% on average) and
      was not affected by treatments, whereas that of lactose and starch was almost
      complete. An increase of dietary NDF level led to an impairment of ADG and feed
      efficiency in the starter (P < 0.002) and in the overall (P < 0.03) fattening
      period. Substitution of starch by lactose linearly decreased (P < 0.001) feed
      efficiency in the starter period and linearly increased (P < 0.001) diarrhea
      incidence in the fattening period. The results indicate that digestive capability
      of early-weaned rabbits is limited and should be taken into account to establish
      optimal levels and sources of carbohydrates in the starter diet.

PMID- 12002310
TI  - Influences of parity and level of feed intake on reproductive response to insulin
      administration after weaning in sows.
AB  - In three experiments, the influence of insulin administered after weaning was
      examined in primiparous sows given extra feed or in primiparous compared to
      multiparous sows. In Exp. 1, 171 primiparous and 231 multiparous crossbred sows
      on a commercial farm were injected with 0.4 IU/kg BW insulin (Eli Lilly Lente
      Iletin II) or saline for 4 d beginning the day after weaning (d 0) and were fed
      2.3 kg/d until mating. In Exp. 2, 153 primiparous sows from the same farm as
      those in Exp. 1 were injected with insulin or saline as in Exp. 1 and were fed
      2.7 or 3.6 kg/d until mating. In Exp. 3, 63 primiparous crossbred sows were
      injected with insulin or saline as described above and fed either 2.3 or 4.5 kg/d
      for 5 d after weaning and were remated. On the commercial farm (Exp. 1 and 2),
      insulin administration increased percentage in estrus for primiparous sows
      compared to multiparous sows (treatment x parity interaction, P < 0.02) but
      tended to lower litter size in primiparous sows (treatment x parity interaction,
      P < 0.06). In Exp. 2, insulin combined with extra feed increased (P < 0.05)
      litter size by two pigs but tended (P < 0.07) to decrease farrowing rate in that
      group (treatment x feed interaction). Weaning-to-estrus interval, pregnancy rate,
      ovulation rate, and embryo survival were not influenced by treatment or feeding
      level (Exp. 3); however, postweaning intake and embryo survival were negatively
      related for saline-treated sows only (r = -0.55; P < 0.01), and backfat depth at
      weaning and embryo survival were positively related for insulin-treated sows only
      (r = 0.44; P < 0.05). Overall, insulin administration differentially influenced
      reproduction in primiparous sows and may have interacted with metabolic or
      nutritional state of the animal.

PMID- 12002311
TI  - Effects of ketoprofen alone or in combination with local anesthesia during the
      castration of bull calves on plasma cortisol, immunological, and inflammatory
      responses.
AB  - To determine the effects of the anti-inflammatory ketoprofen, alone or with local
      anesthesia (LA) during castration on cortisol, immune, and acute phase responses,
      40 Friesian calves (215 +/- 3.5 kg) were assigned as follows: 1) control, 2)
      surgical castration (SURG), 3) SURG following ketoprofen (3 mg/kg BW i.v.; SURG +
      K), 4) SURG following LA (9 mL of 2% lidocaine hydrochloride to each testis; SURG
      + LA), or 5) SURG following LA and K (SURG + LA + K). Total cortisol response was
      greater (P < 0.05) in SURG, SURG + LA, and SURG + K + LA calves than in control
      calves and was not different between control and SURG + K calves. The interval to
      peak cortisol was longer (P < 0.05) for SURG + K + LA calves than for either SURG
      or SURG + K calves. On d 3, KLH-induced interferon-gamma production was lower (P
      < 0.05) in SURG calves than in control calves, whereas concanavalin A-induced
      interferon-gamma production was lower (P < 0.05) in all castration groups than in
      control. On d 1 after surgery, fibrinogen was higher (P < 0.05) in SURG and SURG
      + LA calves than in control calves, whereas SURG + LA + K calves had lower (P <
      0.05) fibrinogen than did SURG calves. Haptoglobin was higher (P < 0.05) in SURG
      calves on d 1, 3, and 7 than in control calves. On d 1 after surgery, SURG + K
      and SURG + LA + K calves had lower (P < 0.05) haptoglobin concentrations than
      SURG calves, whereas SURG + K calves had lower (P < 0.05) levels than SURG calves
      on d 3. In conclusion, surgical castration induced a significant elevation in
      cortisol secretion; the rise in cortisol was reduced to control levels by the
      administration of ketoprofen but not local anaesthetic. Thus, systemic analgesia
      using ketoprofen is more effective than local anesthesia during castration to
      alleviate the associated stress response.

PMID- 12002312
TI  - Effects of melengestrol acetate on reproductive behavior and concentrations of LH
      and testosterone in bulls.
AB  - We investigated the use of an orally active progestin (melengestrol acetate; MGA)
      to suppress reproductive activity in yearling beef bulls. Twenty-four crossbred
      bull calves were given a daily dose of 0, 0.5, 1.0, or 2.0 mg MGA for 99 d.
      Pulsatile patterns of LH and concentrations of testosterone and MGA were
      characterized on d 8, 36, 63, and 92 of the experiment. Numbers of aborted
      mounts, mounts with intromission, total mounts, and flehmen responses were
      assessed on d 15, 43, 71, and 99. Plasma concentrations of MGA were proportional
      to dose of MGA. Melengestrol acetate did not consistently affect mounting
      behavior in a dose-related manner, but, on d 99, number of total mounts for MGA
      treated bulls was lower (P = 0.07) than that for control bulls. On d 15, MGA
      suppressed (P = 0.07) numbers of flehmen responses in a dose-dependent manner,
      but this effect was not sustained throughout the experiment. On d 8,
      concentrations of testosterone in control bulls were higher (P = 0.02) than in
      MGA-treated bulls, but this effect was not observed at other time periods.
      Overall, MGA caused slight decreases in mean concentrations of LH (P = 0.09) and
      LH pulse frequency (P = 0.06). Scrotal circumference was not affected by MGA.
      None of the behavioral traits was correlated with mean concentrations of LH or LH
      pulse frequency. Mounting activity was not correlated with testosterone
      concentrations, but number of flehmen responses was positively correlated with
      testosterone concentrations (P = 0.01). These results fail to support the
      hypothesis that progestins impair male sexual behavior or fertility in males.

PMID- 12002313
TI  - Relationship between postpartum changes in 13, 14-dihydro-15-keto-PGF2alpha
      concentrations in Holstein cows and their susceptibility to endometritis.
AB  - Uterine infections (i.e., endometritis) can have a major economic impact on dairy
      production. Identifying cows that are susceptible to endometritis and improving
      the diagnosis of endometritis could lead to a reduction in the impact of such
      infections. Thus, we used Holstein cows to determine whether postpartum changes
      in 13, 14-dihydro-15-keto-PGF2alpha (PGFM), a metabolite of PGF2alpha, could be
      used to identify cows that are susceptible to endometritis and to improve the
      diagnosis of endometritis. Cows were assigned to three treatments. 1) Control (n
      = 10) had no clinical or bacteriological signs of endometritis during the study.
      2) Treated (n = 11) developed endometritis spontaneously and were treated i.m.
      with 25 mg of PGF2alpha immediately after clinical diagnosis (d 17.6 +/- 0.8
      postpartum; mean +/- SEM). 3) Untreated (n = 10) developed endometritis
      spontaneously and were not treated after diagnosis (d 20.0 +/- 0.5). Examinations
      of external and internal genitalia and bacteriological data were used to diagnose
      endometritis. From d 0 (calving) until approximately d 63 postpartum, jugular
      blood was collected three times weekly. Progesterone and PGFM were quantified in
      plasma. For PGFM, the treatment x day interaction was significant (P < 0.01).
      Overall PGFM profiles for Control and Treated differed (P < 0.05), but the
      Untreated profile did not differ from either Control or Treated. To better
      understand the interaction, PGFM data from d 0 to 35 postpartum were partitioned
      into consecutive 7-d periods, and d-36 and greater data were partitioned into one
      period. Effects of treatment, day, and the treatment x day interaction were then
      evaluated within period. Except for the d-15 to -21 period, PGFM was greater (P <
      0.03) in Control than in Treated and Untreated. In Treated and Untreated, PGFM
      increased during the d-15 to -21 period. For progesterone, treatment did not
      affect the profiles, but day was significant (P < 0.001). Progesterone
      concentrations were basal from d 0 until approximately d 12, and they generally
      increased after d 12. Onset of endometritis was associated with increased
      progesterone concentrations. Treatment did not affect the interval from calving
      to first detected estrus (29.5 +/- 4.9 d) or from calving to AI (73.3 +/- 8.7 d).
      We conclude that PGFM measures have the potential to be used to identify cows
      that are more likely to develop endometritis and that PGFM may aid in the
      diagnosis of endometritis.

PMID- 12002314
TI  - Regulation of hepatic insulin-like growth factor I leader exonusage in lambs:
      effect of immunization against growth hormone-releasing factor and subsequent
      growth hormone treatment.
AB  - The establishment of a GH-responsive endocrine IGF-I network is essential for the
      regulation of postnatal growth. Transcripts of exons 1 and 2 of the mammalian IGF
      I gene are alternately spliced onto exon 3, generating class 1 and class 2 mRNA,
      respectively, each encoding individual signal peptides. The liver is largely
      responsible for the synthesis of circulating IGF-I and is the main site of
      expression for class 2 mRNA. The aim of this study was to examine the regulation
      of hepatic class 1 and 2 mRNA levels in response to changed GH status. Lambs were
      actively immunized against GRF to suppress GH secretion; hepatic IGF-I mRNA
      leader exon usage was examined in the presence and absence of GH replacement and
      in control-immunized lambs. Lambs immunized against GRF exhibited a 17% (P <
      0.001) decrease in growth rate as assessed by whole body weight gain, accompanied
      by decreased circulating IGF-I concentrations (P < 0.001), which were increased
      by subsequent GH treatment (P < 0.001). Hepatic class 1 and 2 IGF-I mRNA levels
      decreased in GRF-immunized lambs, although only class 2 transcripts decreased
      significantly (P < 0.001). Subsequent GH treatment induced increases in class 1
      and 2 mRNA levels (P < 0.001) but the increase in class 2 message exceeded that
      for class 1 (P < 0.001). Thus, the percentage of total IGF-I mRNA accounted for
      by class 2 mRNA was 45% in control lambs, decreased to less than 20% in GRF
      immunized lambs, but increased to 72% in the GRF-immunized lambs treated with GH
      and correlated with circulating IGF-I concentrations. These data suggest
      physiological significance for class 1 and 2 IGF-I mRNA species in GH action.
      Possible functions for such alternative splicing mechanisms are discussed.

PMID- 12002315
TI  - Effect of body fat mass and nutritional status on 24-hour leptin profiles in
      ewes.
AB  - This study was designed to determine the effect of feeding or fasting of fat or
      thin ewes on 24-h leptin profiles. Ewes were assigned, based on ultrasonic
      assessments of last-rib subcutaneous fat measurements, into fat (fat thickness >
      1 cm; mean = 1.52 +/- 0.03 cm; range 1.14 to 2.18 cm) or thin (fat thickness < 1
      cm; mean = 0.25 +/- 0.03 cm; range 0.03 to 0.84 cm) groups. Fat and thin ewes
      were then assigned to either fed or fasted (deprived of feed) groups consisting
      of five ewes per group. Thus, four groups existed and were designated as fat-fed,
      fat-fasted, thin-fed, and thin-fasted. Fed ewes had ad libitum access to feed
      throughout the study. Fasted ewes were prohibited access to feed beginning 48 h
      preceding the experiment. Plasma samples were collected for leptin analysis from
      ewes every 15 min for 24 h beginning 48 h after the initiation of feed
      restriction or the congruent interval in fed ewes. Data were subjected to CLUSTER
      pulse analysis procedures. Profiles of plasma concentrations of leptin were
      episodic in nature and did not differ in a diurnal manner. Fed ewes had greater
      mean concentrations of leptin, area under the curve, number of peaks, peak
      height, peak nadir, and a shorter interval between peaks than fasted ewes (P < or
      = 0.05). Fat ewes had greater mean concentrations of leptin, area under the
      curve, number of peaks, peak height, peak nadir, and a shorter interval between
      peaks than thin ewes (P < 0.02). There also was a tendency for a body condition x
      treatment interaction for number of peaks (P = 0.073) and interval between peaks
      (P = 0.056). These results provide evidence that plasma concentrations of leptin
      are episodic in nature and are influenced by nutritive state and fat thickness
      over the ribs, but display no circadian variation.

PMID- 12002316
TI  - Lactational performance of first-parity transgenic gilts expressing bovine alpha
      lactalbumin in their milk.
AB  - The goal of this study was to determine whether the presence of the bovine alpha
      lactalbumin transgene in first-lactation gilts enhances lactational performance
      and litter growth. Transgenic and sibling nontransgenic gilts were bred to
      nontransgenic boars. Litters were standardized to 10 piglets within 24 h of
      farrowing. Milk production was measured by the weigh-suckle-weigh method on d 3,
      6, 9, and 12 of lactation. Bovine alpha-lactalbumin was present in the colostrum
      and milk of transgenic gilts throughout lactation. The expression of the
      transgene was associated with alterations in composition of mammary secretions,
      especially in early lactation. Lactose concentrations were greater (P < 0.05) in
      mammary secretions of transgenic gilts during the first 12 h postpartum compared
      with controls. In contrast, total solids concentration in mammary secretions from
      transgenic gilts were lower (P < 0.05) relative to controls during the first 6 h
      postpartum. Transgenic gilts produced more milk than controls on d 3, 6, and 9 of
      lactation (P < 0.01). By d 12, differences in milk production between transgenic
      and control sows were no longer different. Lactose intake by transgenic-reared
      litters was greater than lactose intake by control-reared litters on d 6 of
      lactation (P < 0.05). Total solids intake was significantly greater (P < 0.05) by
      transgenic-reared litters on d 3 and 6 compared to control-reared litters. The
      day x genotype interaction on litter weight gain after birth was highly
      significant (P = 0.011), with transgenic-reared litters gaining weight at a
      greater rate than control-reared piglets. Expression of the transgene was
      associated with increased milk production in lactating gilts and increased growth
      of transgenic-reared piglets. Increased lactose synthesis in response to the
      presence of the transgene may result in increased milk production in early
      lactation, leading to increased milk component intake by transgenic litters, and
      ultimately to increased growth of litters reared by first-parity transgenic
      gilts.

PMID- 12002317
TI  - Effects of small peptides or amino acids infused to a perfused area of the skin
      of Angora goats on mohair growth.
AB  - The effect of infusing dipeptides or their amino acids on mohair growth of Angora
      goats was investigated using a skin perfusion technique. Seven Angora wethers
      (average BW 24 +/- 2.5 kg) were implanted bilaterally with silicon catheters into
      the superficial branches of the deep circumflex iliac artery and vein and carotid
      artery. The experiment consisted of three 28-d phases. In the first 14 d of
      Phases 1 and 3, saline was infused into deep circumflex iliac arteries supplying
      skin and in Phase 2 a mixture of dipeptides (methionine-leucine [Met-Leu], lysine
      leucine [Lys-Leu]) was infused into the artery on one side, and free amino acids
      were administered on the other side. Infusion rates of peptides were 0.85 mg/h
      Met-Leu and 0.85 mg/h Lys-Leu in 2.4 mL saline. Infusion rates of amino acids
      were 0.474 mg/h Lys, 0.483 mg/h Met, and 0.743 mg/h Leu in 2.4 mL saline. A 100
      cm2 area within the perfused region was used to determine mohair growth. Two
      weeks after the cessation of infusions, perfused areas were shorn. Clean mohair
      production from the dipeptide- and amino acids-perfused regions were similar
      (4.21 vs 4.35 g/[100 cm2 +/- 28 d], respectively; P > 0.05). However, clean
      mohair production during dipeptides and amino acids infusions was greater (P <
      0.01) than that observed during saline infusions (3.63 g/[100 cm2 +/- 28 d]).
      There were no significant differences between dipeptides and free amino acids in
      concentrations of various hormones and metabolites in blood from deep circumflex
      iliac veins (P > 0.05). In conclusion, the studied small dipeptides and amino
      acids similarly increased mohair fiber growth, presumably through supplying
      limiting amino acids directly to the fiber follicle.

PMID- 12002318
TI  - Utilization of distillers grains from the fermentation of sorghum or corn in
      diets for finishing beef and lactating dairy cattle.
AB  - Beef finishing and dairy lactation experiments were conducted to evaluate the
      nutritional value of distillers grains (DG) from sorghum or corn fermentation, in
      both wet (35.4% DM) and dry (92.2% DM) form (dairy trial only). In the finishing
      experiment, 60 yearling steers were used in a completely randomized design with
      three diets that were fed for 127 d: 1) control diet with 86% (DM basis) dry
      rolled corn and no DG; 2) 30% of ration DM as wet corn DG in place of dry-rolled
      corn; and 3) 30% of ration DM as wet sorghum DG in place of dry-rolled corn. All
      diets contained a minimum of 6.8% degradable intake protein and 13.0% CP. Steers
      fed DG had 10% greater ADG (< 0.01) and 8% greater efficiency of gain (P < 0.01)
      than steers fed the control diet. Wet corn and sorghum DG resulted in similar ADG
      and efficiency of gain. Hot carcass weights, fat thickness, and yield grades were
      greater for steers fed DG than for controls (P < 0.07). Improvements in ADG and
      feed efficiency observed when DG replaced dry-rolled corn indicated that the NEg
      content of wet DG is approximately 29% greater than that of dry-rolled corn. In
      the dairy lactation experiment, 16 lactating Holstein cows (eight multiparous,
      including four fistulated) were used in a replicated 4 x 4 Latin square design
      with 4-wk periods. Corn and sorghum DG were fed at 15% of the ration DM in either
      wet or dry form. Diets were fed as total mixed rations that contained 50% of a
      1:1 mixture of alfalfa and corn silages, 24.3% ground corn, and 9.1% soybean meal
      (DM basis). There was no effect of source or form of DG on DMI, ruminal pH and
      VFA, or in situ digestion kinetics of NDF from DG. Efficiency of milk production
      was unaffected by diet. Corn and sorghum DG resulted in relatively similar
      performance when fed to beef or dairy cattle in this study.

PMID- 12002319
TI  - Influence of abomasal infusion of glucose or partially hydrolyzed starch on
      pancreatic exocrine secretion in beef steers.
AB  - Five crossbred steers (348 +/- 12 kg) fitted with a pancreatic pouch draining the
      main pancreatic duct and duodenal re-entrant and abomasal infusion cannulas were
      used in a 5 x 5 Latin square design to determine the influence of postruminal
      carbohydrate source and level on pancreatic exocrine secretion in beef steers.
      Abomasal infusion treatments (250 mL infused/h) were water (control), 20 g/h
      glucose, 40 g/h glucose, 20 g/h starch hydrolysate (SH), and 40 g/h SH. Infusion
      periods were 8 d with 3 to 4 d of rest between periods. Pancreatic juice was
      collected for 6 h on d 8 of each collection period. Every 30 min a 10% subsample
      was composited and frozen and the remainder was infused into the duodenum via the
      reentrant cannula. Abomasal infusion of glucose or SH increased (P < 0.10) total
      secretion of pancreatic juice and decreased (P < 0.10) secretion of alpha-amylase
      activity. Abomasal carbohydrate infusion did not influence total secretion of
      protein, trypsin activity, or chymotrypsin activity. This experiment indicates
      that increasing postruminal glucose or SH decreases pancreatic alpha-amylase
      secretion.

PMID- 12002320
TI  - Carbohydrate fermentation and nitrogen metabolism of a finishing beef diet by
      ruminal microbes in continuous cultures as affected by ethoxyquin and(or)
      supplementation of monensin and tylosin.
AB  - Long-term feedlot studies have shown positive effects (i.e., improved ADG and
      reduced morbidity and mortality) of dietary supplementation with ethoxyquin
      (AGRADO). This may be due to improving the antioxidant capacity at the ruminal,
      postruminal, or postabsorption levels. This study was designed to investigate the
      role of ethoxyquin at the rumen level. A finishing diet (12.5% CP; DM basis) was
      formulated to contain (on a DM basis) 77.5% flaked corn, 10% corn cobs, 10%
      protein/vitamin/mineral supplement, and 2.5% tallow. In a randomized complete
      block design experiment, the treatments were arranged as a 2 x 2 factorial. The
      main factors were two ethoxyquin treatments (without or with 150 ppm) and two
      monensin/tylosin treatments (without or with monensin and tylosin at 0.0028 and
      0.0014% of dietary DM, respectively). Eight dual-flow, continuous culture
      fermenters were used in two experimental periods (blocks; 8 d each with 5 d for
      adjustment and 3 d for sample collection) to allow for four replications for each
      treatment. No interactions (P > 0.05) were detected for any of the measurements
      evaluated. Therefore, results of the main factors were summarized. Ethoxyquin
      supplementation improved (P < 0.05) true digestibility of OM (from 38.8 to 45.0%)
      but it did not alter (P > 0.05) concentrations of total VFA (averaging 131 mM) or
      acetate (averaging 58.8 mM). Ethoxyquin decreased (P < 0.05) propionate
      concentration from 51.1 to 42.4 mM and increased (P < 0.05) butyrate
      concentration from 18.4 to 22.9 mM. Digestion of total nonstructural
      carbohydrates was not altered (P > 0.05) by the treatments and averaged 86%. With
      the exception of increased (P < 0.05) concentration of propionate (from 42.0 to
      51.5 mM) and decreased (P < 0.05) concentration of butyrate (from 25.9 to 16.3
      mM), no effects (P > 0.05) were detected for monensin/tylosin. Ruminal N
      metabolism, including efficiency of bacterial protein synthesis (averaging 21.2 g
      N/kg OM truly digested), was not affected (P > 0.05) by the treatments. Results
      suggest positive effects of ethoxyquin on ruminal digestion of OM and unique
      changes in VFA production.

PMID- 12002321
TI  - Effect of calf age and dam breed on intake, energy expenditure, and excretion of
      nitrogen, phosphorus, and methane of beef cows with calves.
AB  - The effects of calf age and dam breeds of different milk yield potential on
      turnover of energy and nutrients were followed in 16 Simmental and 16 Angus beef
      cows with Angus-sired calves. Calf ages investigated were 1, 4, 7, and 10 mo. The
      forage offered for ad libitum access consisted of hay for the calves and of a
      constant mixture of grass silage, meadow hay, and straw (1:0.7:0.3 on a DM basis)
      for the cows. Calves of 10 mo of age received an additional 2.6 kg DM/d of
      crushed barley. The animals were kept in groups of four cows and four calves
      except in the respiration chambers, where only one cow (tethered) and her calf
      (loose) were grouped together. Indicator techniques were applied to obtain
      individual data on feces and urine volumes during group housing. In the Simmental
      cows, heavier on average by 22 kg, voluntary DMI was higher than in the Angus
      cows (14.0 vs 12.3 kg/d). In calves, DMI from supplementary feeds was 1.6, 3.9,
      and 6.3 kg/d, on average, at 4, 7, and 10 mo of age, respectively. Dam breed had
      no significant effect on DMI and ADG of calves and on BW changes of cows. System
      retention of energy, N, and P showed a curvilinear development with calf age.
      System energy expenditure, which linearly increased with calf age, was higher
      with Simmental than with Angus dams (11%), even when adjusted for metabolic BW
      (8%). Energy loss through methane linearly increased with NDF intake and,
      consequently, with calf age from 18 to 30 MJ/d (446 to 751 L/d) for cows and
      calves together. Similarly, fecal and urinary N excretion and fecal P excretion
      steadily increased with calf age. In calves, the easily volatile N percentage of
      manure N rapidly decreased from very high levels in young calves. The resulting
      changes in inclination to gaseous N loss during manure storage for 8 wk were more
      than compensated by alterations in N intake of the calves, resulting in an
      increased total system N loss with progressing lactation. Overall, the present
      results indicate a difference between Angus and Simmental in efficiency of
      nutrient and energy utilization that might be explained by the difference in
      amount of delivery of nutrients to the calves via milk vs forage. Suggestions are
      made as to how the emissions of N, P, and methane, which were excessive in
      relation to productivity, could be reduced by nutritional means.

PMID- 12002322
TI  - Effect of extruded full-fat soybeans on conjugated linoleic acid content of
      intramuscular, intermuscular, and subcutaneous fat in beef steers.
AB  - Crossbred Angus steers (n = 30) were used to determine whether the conjugated
      linoleic acid (CLA) content of beef fat could be increased by feeding varying
      levels of extruded full-fat soybeans as a source of polyunsaturated fatty acids
      for rumen biohydrogenation. Diets were as follows: 1) control, 2) 12.7% extruded
      full-fat soybeans (LESB), and 3) 25.6% extruded full-fat soybeans (HE SB). Steers
      were individually housed and fed the diets for 111 d during the finishing period.
      Over the experimental period, treatment groups were similar in ADG (1.7 +/- 0.1
      kg/d) and had a similar slaughter weight (603 +/- 11.6 kg). Dressing percentage
      averaged 61.6% and carcass composition averaged 14.3% protein, 30.9% lipid, and
      54.8% water. At slaughter, the intramuscular, intermuscular, and subcutaneous fat
      depots were sampled from the rib longissimus, eye of round, and chuck tender
      muscles. Across all fat depots, the CLA content differed (P < 0.05), averaging
      6.6, 6.7, and 7.7 mg/g of fatty acids for the control, LESB, and HESB diets,
      respectively. There were significant differences in CLA content between fat
      depots within a cut, but differences were relatively small and the hierarchy in
      fat depots was not consistent among cuts. The cis-9, trans-11 isomer was the
      predominant CLA isomer and its content in fat was related to trans-11 C18:1
      content (r = 0.53; P < 0.001). There was substantial individual variation in CLA
      content and this varied from 2.6 to 17.0 mg/g fatty acids across all treatments
      and fat depots. Overall, results demonstrated that including extruded full-fat
      soybeans in the diet of finishing steers increased the CLA content of beef fat.
      Differences were relatively small and the relationship of this to rumen
      fermentation and endogenous synthesis of CLA is considered.

PMID- 12002323
TI  - Nutritional quality of extruded kidney bean (Phaseolus vulgaris L. var. Pinto)
      and its effects on growth and skeletal muscle nitrogen fractions in rats.
AB  - The influence of extrusion cooking on the protein content, amino acid profile,
      and concentration of antinutritive compounds (phytic acid, condensed tannins,
      polyphenols, trypsin, chymotrypsin, alpha-amylase inhibitors, and
      hemagglutinating activity) in kidney bean seeds (Phaseolus vulgaris L. var.
      Pinto) was investigated. Growing male rats were fed diets based on casein
      containing raw or extruded kidney beans with or without methionine
      supplementation for 8 or 15 d. Rates of growth, food intake, and protein
      efficiency ratio were measured and the weight of the gastrocnemius muscle and the
      composition of its nitrogenous fraction was determined. Extrusion cooking reduced
      (P < 0.01) phytic acid, condensed tannins, and trypsin, chymotrypsin, and (alpha
      amylase inhibitory activities. Furthermore, hemagglutinating activity was
      abolished by extrusion treatment. Protein content was not affected by this
      thermal treatment. Rats fed raw kidney bean lost BW rapidly and the majority died
      by 9 d. Pretreatment of the beans by extrusion cooking improved food intake and
      utilization by the rats and they gained BW. Supplementation of extruded kidney
      bean with methionine further enhanced (P < 0.01) food conversion efficiency and
      growth. However, BW gains and muscle composition still differed (P < 0.01) from
      those of rats fed a high-quality protein.

PMID- 12002324
TI  - Effect of chlortetracycline in a trace mineral salt mix on fertility traits in
      beef cattle females in Florida.
AB  - The study objective was to determine the effect of chlortetracycline in an ad
      libitum trace-mineralized salt mix given to heifers before and(or) during bull
      exposure on the proportion pregnant and the time to conception in a fixed
      breeding period. Heifers (n = 768), 13 to 15 mo of age, were individually
      identified, immunized (Leptospira, Campylobacter fetus), examined (body condition
      score, vaginal lesion score, BW), and randomly allocated within 2 x 2 factorial
      blocks of treatments where trace mineral salt with and without chlortetracycline
      medication was provided in similar but nonadjacent pastures either before and(or)
      during bull exposure. The chlortetracycline feeding period was about 30 d for
      each. In the 2 d immediately before bull exposure, heifers were examined (body
      condition score, vaginal lesion score, reproductive tract evaluation) and
      reallocated to treatment pastures. Pregnancy was determined by per rectal
      palpation at 45 d following bull removal. Mineral intake was below that expected
      for heifer groups and, as a result, chlortetracycline intake was estimated at
      less than one-third of that targeted. Many heifers were not cycling
      reproductively at the onset of bull exposure (n = 456, 60.3%, based on a
      reproductive tract score < 3). Despite these limitations, heifers receiving
      chlortetracycline treatment before breeding had a pregnancy percentage of 65%
      (chlortetracycline before and during breeding 67% and chlortetracycline before
      breeding 61.8%) compared to those receiving no treatment before breeding (53%, P
      < 0.03; no chlortetracycline before or during breeding 60.4% and
      chlortetracycline during breeding 47.4%). Heifers receiving chlortetracycline
      treatment before breeding were 57% more likely to become pregnant than those not
      treated before breeding. Change in vaginal lesion score was associated with the
      proportion pregnant, but neither body condition score nor average daily gain
      were.

PMID- 12002325
TI  - Reflectance spectrum of adipose tissue to trace grass feeding in sheep: influence
      of measurement site and shrinkage time after slaughter.
AB  - The signature of carotenoid pigments stored in the caudal fat has been used to
      discriminate carcasses of lambs raised on pasture from those fed concentrates.
      However, the literature reports higher concentration of carotenoids in perirenal
      than in caudal fat, and it is likely that carotenoid concentration in fat
      increases with shrinkage time. Our objectives were to investigate the effects of
      measurement site and shrinkage time after slaughter on the reliability of the
      discrimination between grass- and concentrate-fed lambs. Thirty-two lambs were
      fed concentrate-based diets (stall, n = 16) or grazed a natural pasture in France
      (grass, n = 16). The concentrate supply was regulated to have similar ADG between
      the two treatments. Periodically lambs weighing about 35 kg were slaughtered.
      Reflectance spectrum and lightness (L*), redness (a*), and yellowness (b*) were
      measured at slaughter and after 24 h of shrinkage in the subcutaneous caudal and
      in the perirenal fat. The spectra were translated to have a value of reflectance
      at 510 nm = 0 and the integral of the translated spectrum was calculated between
      450 and 510 nm (i.e., the zone of light absorption by carotenoids). The integral
      value of subcutaneous caudal fat at slaughter differed between stall- and grass
      fed lambs (P < 0.05) but was not reliable to discriminate between feeding
      treatments. After 24-h shrinkage, the discrimination was better but was uncertain
      for 50% of the lambs. The integral value of perirenal fat at slaughter allowed us
      to discriminate all the lambs fed concentrates (16) from all those fed pasture
      (16). After 24-h shrinkage, the discrimination based on perirenal fat was
      partially compromised; 21.9% of the animals were not correctly discriminated. The
      integral value of the translated spectrum was highly (P < 0.001) correlated with
      the fat yellowness (b*), but the b* value was not reliable to discriminate
      between feeding treatments. However, plotting yellowness (b*) against redness
      (a*) values allowed us to discriminate 31 out of 32 lambs. Measuring reflectance
      spectrum of perirenal fat at slaughter allowed for complete discrimination of
      grass-fed from stall-fed lambs. However, because the integral values were
      affected by shrinkage time, measurements should be rigorously made immediately
      after slaughter.

PMID- 12002326
TI  - Effect of frequency of boar exposure and adjusted mating times on measures of
      reproductive performance in weaned sows.
AB  - In weaned sows, reduced reproductive performance can result from failure or
      delayed return to estrus or improper timing of insemination. This experiment
      evaluated the effect of increased frequency of boar exposure and adjusted mating
      times on reproductive performance. Sows of mixed parity were weaned approximately
      18.7 d after parturition and allotted by genotype, parity, and lactation length
      to boar exposure frequency of once daily (1X, n = 66), twice daily every 12 h
      (2X, n = 61), or three times daily exposure at 8-h intervals (3X, n = 60). Sows
      were weaned into crates and boar exposure was initiated 3 d after weaning. Once
      estrus was detected, ultrasound was performed every 8 h to determine time of
      ovulation. All sows were artificially inseminated twice in the 1X group at 0 and
      24 h, in the 2X group at 12 and 24 h, and in the 3X group at 16 and 32 h after
      onset of estrus. The weaning-to-estrus interval was not influenced by treatment
      and averaged 4.5 d. The percentage of sows expressing estrus in 8 d was higher (P
      < 0.05) for 1X (97.3%) compared with 2X (92.8%) but not the 3X group (94.0%). The
      percentage of sows ovulating after estrus was not influenced by treatment (P >
      0.10) and averaged 96.5%. Estrus-to-ovulation interval was not affected by
      treatment (44.7 h) but was influenced by weaning-to-estrus interval (P < 0.0001).
      Length of estrus was influenced by treatment (P < 0.001), with estrus in the 1X
      (46.6 h) shorter than in the 2X (60.0 h) and 3X (67.0 h) treatments, and also by
      weaning-to-estrus interval (P < 0.001). The percentage of first inseminations
      occurring within 24 h before ovulation was increased (P < 0.001) in the 2X (62%)
      and 3X (66%) groups compared with the 1X group (28%) and was also influenced by
      parity (P < 0.001) and weaning-to-estrus interval (P < 0.05). The percentage of
      second services within 24 h before ovulation was not increased by any factor and
      averaged 78%. Farrowing rates were not increased (P > 0.10) for 2X (87.2%) and 3X
      (83.1%) treatments compared with 1X (75.0%). Total pigs born was also not
      affected by treatment, although 2X (11.2) and 3X (10.7) numbers were greater than
      1X (10.0). It appears that once-daily estrus detection combined with delayed
      mating could achieve optimal reproductive performance.

PMID- 12002327
TI  - Effect of an accelerated finishing program on performance, carcass
      characteristics, and circulating insulin-like growth factor I concentration of
      early-weaned bulls and steers.
AB  - Sixty-three Angus x Simmental calves were allotted to a bull or a steer group
      based on sire, birth date, and birth weight to determine effects of castration
      status on performance, carcass characteristics, and circulating insulin-like
      growth factor I (IGF-I) concentrations in early-weaned cattle. At 75 d of age,
      calves in the steer group were castrated. Calves were not creep-fed prior to
      weaning. All calves were weaned and weighed at an average age of 115 d and
      transported by truck to the OARDC feedlot in Wooster, OH. Performance and carcass
      characteristics were measured in three phases. Phase 1 was from 115 to 200 d of
      age, phase 2 was from 201 to 277 d of age, and phase 3 was from 278 d of age to
      slaughter. Before implantation, four bulls and four steers were selected for
      serial slaughter and carcass evaluation. Steers were implanted with Synovex-C at
      130 d of age and with Revalor-S at 200 and 277 d of age. Serum samples were
      collected from all calves on the day of implantation, 28 and 42 d after
      implantation, and at slaughter and analyzed for circulating IGF-I concentration.
      Bulls gained 9.7% faster (1.75 vs 1.60 kg/d; P < 0.01), consumed 25 kg more DM
      (521 vs 496 kg; P = 0.11), and were 3.3% more efficient (282 vs 273 g/kg, P <
      0.10) than steers in phase 1. However, steers gained 10.5% faster (1.62 vs 1.46
      kg/d; P < 0.02), consumed similar amounts of DM, and were 6.5% more efficient
      than bulls (214 vs 201 g/kg; P < 0.06) in phase 2. Overall gains and efficiency
      were similar between bulls and steers; however, bulls consumed 140 kg more DM (P
      < 0.05), were 27 kg heavier (P < 0.05), and had to stay in the feedlot 18 more
      days (P < 0.05) than steers to achieve a similar amount of fat thickness.
      Implanted steers had greater concentrations of circulating IGF-I than bulls (P <
      0.01), and the pattern of IGF-I concentration over time was affected by
      castration status (castration status x time interaction; P < 0.01). Synovex-C had
      a lower impact on circulating IGF-I concentration (implant effect, P < 0.01) than
      either Revalor-S implant. Eighty-five percent of both bulls and steers had
      marbling scores sufficient to grade low Choice or better. Bulls achieved their
      target fat thickness later, increased muscle growth, and deposited fat more
      favorably than steers, possibly due to a gradual increase in IGF-I concentration
      as the testicles grew rather than the large fluctuations in IGF-I concentration
      observed in steers following implantation.

PMID- 12002328
TI  - Preweaning growth of F1 tropically adapted beef cattle breeds x Angus and
      reproductive performance of their Angus dams in arid rangeland.
AB  - The objective of this study was to determine the preweaning performance of F1
      Brahman (Bos indicus)-, Senepol (Bos taurus)-, and Tuli (Sanga)-Angus calves
      under semiarid south Texas conditions and to evaluate the reproductive
      performance of their Angus dams. Four hundred eighty-nine records collected over
      4 yr were analyzed. The statistical model for performance traits included the
      effects of breed of sire, year, sex, age of dam, and breed of sire x year. Year
      effects were important (P < 0.05) for performance traits but could be explained,
      at least partially, by differences between years in rainfall patterns. Brahman F1
      calves were 13% less (P < 0.05) vigorous at birth, 4.7 kg heavier (P < 0.05) at
      birth, 13.5 kg heavier (P < 0.05) at weaning, 0.25 units lower (P < 0.05) in body
      condition score (BCS) at weaning, and 1.75 units greater (P < 0.05) in frame
      score (scores of 1 to 9) at weaning than Tuli and Senepol F1 calves. Senepol F1
      calves were intermediate (P < 0.05) between the Brahman and Tuli F1 calves for
      birth and weaning weight but had 11% more (P < 0.05) vigor at birth than the
      other two crossbreds. Tuli and Senepol F1 were similar (P > 0.05) in BCS and
      frame size at weaning. Males were 3.3 kg heavier (P = 0.12) at birth than
      females, especially for the F1 Brahman males that were 4.5 kg heavier (P < 0.05)
      than their counterparts. Brahman F1 weaned 19.9 kg heavier (P < 0.05) than the
      average of the other two F1 in the year of the greatest rainfall (1994), whereas
      the average advantage in other years was 11.4 kg. This difference gave rise to a
      breed of sire x year interaction (P < 0.003). Brahman F1 were heavier at every
      measurement and appeared to be later-maturing and more able to excel under good
      forage conditions than the other two F1 breed types; Senepol and Tuli F1 were
      similar (P > 0.05) in these respects but appeared to be more competitive in
      relative growth rate to the Brahman F1 calves in years of greater nutritional
      stress. Angus females were observed to have a relatively low reproductive rate
      and high apparent fetal loss at the first (27.5%) and second (19.2%) compared
      with the third or later pregnancy (11.2%). Angus females that gave birth to
      Brahman F1 calves had 20.1% lower (P < 0.05) pregnancy rates in the succeeding
      year than those that had given birth to the other two breeds.

PMID- 12002329
TI  - The use of passive injectable transponders in fattening lambs from birth to
      slaughter: effects of injection position, age, and breed.
AB  - A total of 1,159 Tiris half-duplex passive injectable transponders (PIT) of 32-mm
      length were used to study the electronic identification of 618 fattening lambs of
      two breeds used for different production purposes (Ripollesa, meat breed, n =
      271, and Manchega, dairy breed, n = 347). The lambs were s.c. injected in the
      armpit and the retro-auricular positions at 2, 15, and 30 d of age. All lambs
      were also tagged with a small plastic ear tag after birth. A group of 76 lambs
      were injected only in the right armpit and were kept for breeding. The PIT
      losses, breakages, and electronic failures were evaluated at weekly weight
      recordings throughout the fattening period using two types of hand-held
      transceivers. Fattened lambs were harvested in a commercial abattoir between 3
      and 4 mo of age when they reached market weight (11 to 12 kg hot carcass weight).
      The total number of PIT that fell or broke in the slaughtering line, the location
      method, and the recovery time were recorded. On the farm PIT losses were not
      affected (P > 0.05) by age at injection, injection position, or breed. Mean
      losses of PIT and ear tags during the same period were 5% and 6.3%, respectively
      (P > 0.05). No PIT breakages or failures were observed during the fattening
      period. Mean recovery of PIT in the abattoir (85.6%) was affected (P < 0.05) by
      breed and injection position. Losses of PIT in the abattoir were greater (P <
      0.05) in the Ripollesa breed (18.4%) than in Manchega (10.0%), and for both
      breeds losses were greater (P < 0.05) in the retro-auricular than in the armpit
      positions (18.6 vs 10.8%, respectively). The percentage of PIT broken during
      slaughtering was low (0.3%). The mean recovery times (18 +/- 2 s) were not
      affected (P > 0.05) by breed, injection position, or age, thus allowing a
      harvesting speed of 200 lambs/h on average. In conclusion, the injection of 32-mm
      PIT into the armpit or the retro-auricular region is not recommended as a
      practice for the electronic identification of fattening lambs, even though they
      perform similarly to small plastic ear tags. This is partly a consequence of the
      PIT losses observed on the farm but mainly because of the difficulties with
      recovering the PIT in the abattoir. More research will determine whether the use
      of smaller transponders or injection in other positions could improve their
      performance in fattening lambs.

PMID- 12002330
TI  - Effects of supplemental vitamin E on performance, health, and humoral immune
      response of beef cattle.
AB  - Three experiments were conducted to examine the effect of dietary vitamin E on
      receiving performance and health and on finishing performance of beef cattle. One
      hundred twenty beef steers (Exp. 1; initial BW = 173 kg) and 200 beef heifers
      (Exp. 2; initial BW = 204 kg) were assigned randomly to one of three treatment
      diets formulated to supply 285, 570, or 1,140 IU/animal daily of supplemental
      vitamin E during the receiving period. Average daily gain, gain:feed, and DMI
      were calculated every 14 d, with pen as the experimental unit. Morbidity and
      retreatment data were analyzed using a nonparametric procedure. After the
      receiving period, cattle were assigned to a grazing period followed by a
      finishing program and fed until slaughter. In Exp. 3, 17 beef steers were used to
      evaluate effects of the same three vitamin E levels on humoral immune response to
      an ovalbumin vaccine given on d 0 and 14. Jugular blood samples were collected on
      d 0, 7, 14, and 21. In Exp. 1, vitamin E did not affect (P > 0.10) ADG, DMI, or
      gain:feed for d 0 to 14, 14 to 28, or 0 to 28. No effects were noted for
      percentage of morbidity; however, cattle receiving 1,140 IU/d had a numerically
      (P = 0.15) lower incidence of retreatment. During the 91-d finishing phase, a
      quadratic effect (P < 0.08) was noted for DMI, ADG, backfat thickness,
      longissimus muscle area, and yield grade. In Exp. 2, a tendency for a linear (P =
      0.10) increase in ADG was observed for the first 14 d of receiving; however, ADG
      decreased linearly (P = 0.06) with vitamin E concentration thereafter. For the 28
      d period, ADG and DMI did not differ among treatments, but gain:feed decreased
      linearly (P < 0.05) for d 14 to 28 and for d 0 to 28. No effects on percentage
      morbidity were noted in Exp. 2, and no differences were detected for ADG,
      gain:feed, or DMI for the 98-d finishing period. There was a linear increase in
      yield grade (P < 0.05) and a linear (P < 0.08) decrease in longissimus muscle
      area with increasing vitamin E. Heifers receiving 570 IU of vitamin E during the
      receiving period tended to have a higher (P < 0.09) dressing percentage at
      slaughter. In Exp. 3, no significant differences were detected in serum IgG
      titers to ovalbumin on d 0, 7 or 14; however, on d 21, a linear increase (P =
      0.07) in serum IgG titers was noted with supplemental vitamin E. Supplemental
      vitamin E had limited effects on performance; however, effects on humoral immune
      response and recovery from respiratory disease warrant further research.

PMID- 12002331
TI  - Genetic diversity and assignment tests among seven French cattle breeds based on
      microsatellite DNA analysis.
AB  - Genetic variability and relationships among six native French cattle breeds
      (Abondance, Tarentaise, Villard de Lans, Montbeliarde, Limousin, and Charolais)
      and one foreign breed (Holstein) were investigated using 23 microsatellite
      markers. These breeds were also compared with four Swiss breeds genotyped in a
      previously published study. Interestingly, the French alpine breeds have smaller
      population sizes but showed higher genetic variability than the larger Holstein
      breed. Neighbor-joining trees and PCA (principal components analysis) showed that
      alpine breeds tend to cluster together. Abondance and Tarentaise breeds were
      closely related, whereas the Holstein was highly differentiated from all breeds
      analyzed. Two different assignment tests for determining the breed of origin of
      individuals were compared: "direct" and "exclusion-simulation" approaches. The
      exclusion-simulation significance test correctly assigns fewer individuals than
      the direct approach but provides a confidence level (e.g., P < 0.01) for each
      individual being assigned. Accurate assignment with high statistical confidence
      is required for animal traceability. Unfortunately, the accuracy of assignment
      greatly decreases as the threshold level of confidence of assignment increases
      (e.g., from P < 0.05 to P < 0.001). Assignment accuracy also greatly declines as
      the level of population differentiation decreases below the level often found
      between related breeds (e.g., F(ST) < 0.1).

PMID- 12002332
TI  - Genetic evaluation of the probability of pregnancy at 14 months for Nellore
      heifers.
AB  - To estimate the heritability for the probability that yearling heifers would
      become pregnant, we analyzed the records of 11,487 Nellore animals that
      participated in breeding seasons at three farms in the Brazilian states of Sao
      Paulo and Mato Grosso do Sul. All heifers were exposed to a bull at the age of
      about 14 mo. The probability of pregnancy was analyzed as a categorical trait,
      with a value of 1 (success) assigned to heifers that were diagnosed pregnant by
      rectal palpation about 60 d after the end of the breeding season of 90 d and a
      value of 0 (failure) assigned to those that were not pregnant at that time. The
      estimate of heritability, obtained by Method R, was 0.57 with standard error of
      0.01. The EPD was predicted using a maximum a posteriori threshold method and was
      expressed as deviations from 50% probability. The range in EPD was -24.50 to
      24.55%, with a mean of 0.78% and a SD of 7.46%. We conclude that EPD for
      probability of pregnancy can be used to select heifers with a higher probability
      of being fertile. However, it is mainly recommended for the selection of bulls
      for the production of precocious daughters because the accuracy of prediction is
      higher for bulls, depending on their number of daughters.

PMID- 12002333
TI  - Quantitative analysis of beta-adrenergic receptor subtypes in pig tissues.
AB  - The density and distribution of beta1- and beta2-adrenergic receptors (betaAR) in
      porcine adipocytes, skeletal muscle, heart, lung, and liver were investigated
      using competitive displacement of ligand binding with subtype-selective ligands.
      Three experimental approaches were used to estimate the distribution of betaAR
      subtypes in adipocytes. Two approaches involved simultaneous linear regression
      analysis of multiple competitive displacement curves with the beta1AR-selective
      antagonist CGP 20712A and the beta2AR-selective ligand BRL 37344. For the third
      approach, radioligand saturation assays were perfomed using a concentration of
      CGP 20712A that completely blocked the beta1AR. All three approaches indicated
      the presence of multiple betaAR subtypes in porcine adipocytes and gave similar
      estimates for the proportion of these subtypes. Saturation assays in the presence
      of the beta1AR blocker CGP 20712A were conducted to determine the distribution of
      the betaAR subtypes in skeletal muscle, heart, lung, and liver. The proportions
      of the beta1AR and beta2AR were 81:19, 59:41, 72:28, 58:42, and 50:50 for
      adipose, skeletal muscle, heart, lung, and liver, respectively. These estimates
      based on receptor protein were consistent with published estimates of mRNA
      abundance in pig tissues but differ from estimates for other species. The
      predominance of beta1AR in adipocytes and skeletal muscle may contribute to the
      reduced efficacy of select betaAR agonists in pigs compared to other species
      because most of the ligands evaluated in growth studies are purported to be
      beta2AR selective. The density of the betaAR varied among tissues in the
      following order: heart = lung > adipocytes > skeletal muscle or = liver.

PMID- 12002334
TI  - Effect of vitamin D3 supplementation level on the postmortem tenderization of
      beef from steers.
AB  - The objective of this experiment was to determine the effect of different doses
      of vitamin D3 (VITD) on beef feedlot performance, plasma and muscle Ca2+, tissue
      residues, and improvement of Warner-Bratzler shear force (WBS) and panel
      tenderness. A total of 167 steers were fed one of six levels of VITD. The VITD
      treatments (28 steers/treatment) were 0, 0.5 x 10(6), 1 x 10(6), 2.5 x 10(6), 5 x
      10(6), and 7.5 x 10(6) IU/steer daily of VITD fed nine consecutive days before
      slaughter. Feedlot performance and plasma Ca2+ were measured during the last 21
      days on feed. Warner-Bratzler shear force was measured on strip loin and top
      round steaks at 7, 10, 14, and 21 d postmortem. The VITD treatments of 5 and 7.5
      x 10(6) IU/steer daily decreased (P < 0.05) ADG, and VITD supplementation of 2.5,
      5, and 7.5 x 10(6) IU/steer daily decreased average dry matter feed intake (P <
      0.05) at the end of the feeding trial. Plasma Ca2+ increased linearly with VITD
      treatment (P < 0.01). Calpastatin and calpain activity were not influenced by
      treatment (P > 0.05), but muscle Ca2+ was increased (P < 0.05) by VITD treatments
      of 1, 2.5, 5, and 7.5 10(6) IU/steer daily. Feeding VITD did not influence (P >
      0.05) carcass quality or yield traits. Supplementing VITD at levels of 1, 2.5, 5,
      and 7.5 10(6) IU/steer daily increased (P < 0.05) VITD concentrations in strip
      loin and liver samples. Cooking liver decreased VITD concentrations 10 to 28%.
      Vitamin D3 treatments of 0.5 and 7.5 x 10(6) IU/d reduced strip loin steak WBS at
      d 7 (P < 0.05), but VITD treatments did not decrease strip loin steak WBS at any
      other time postmortem. The VITD treatments of 0.5, 1, and 5 x 10(6) IU/steer
      daily decreased top round steak WBS at 7 d, and all VITD treatments decreased 10
      d top round steak WBS (P < 0.05). Supplementing steers with 0.5 x 10(6) IU/steer
      daily of VITD also decreased (P < 0.05) top round steak WBS at 21 d postmortem
      compared with controls. Sensory tenderness at 7 d postmortem was increased (P <
      0.05) by all VITD treatments in top round steaks, yet strip loin tenderness
      scores were not affected (P > 0.05) by VITD treatment. Treatment with VITD
      quadratically decreased (P < 0.05) round WBS. Thus, VITD treatment will
      effectively improve tenderness when cattle tend to be tough and have no impact on
      cattle that produce tender beef. Feeding steers 0.5 x 10(6) IU of VITD daily for
      9 d improved tenderness in two muscles without negatively affecting feedlot
      performance or tissue residues.

PMID- 12002335
TI  - Technical note: Sampling methodology for relating sarcomere length, collagen
      concentration, and the extent of postmortem proteolysis to beef and pork
      longissimus tenderness.
AB  - The objective of this study was to determine the effect of sampling methodology
      on the relationship between longissimus tenderness and measures of biochemical
      meat traits. Sampling methodology included measurements of sarcomere length,
      collagen concentration, and postmortem desmin proteolysis on raw samples and
      measurements of these same traits on the same cooked meat used for shear force
      measurement. Twenty crossbred steers and 20 crossbred barrows were used for these
      studies. The beef longissimus thoracis were vacuum-packaged, stored at 2 degrees
      C until 14 d postmortem, then frozen and stored at -30 degrees C. The pork
      longissimus thoracis et lumborum were vacuum-packaged, stored at 2 degrees C
      until 7 d postmortem, then frozen and stored at -30 degrees C. Trained sensory
      panel tenderness rating ranged from 3.1 to 7.6 for beef and 4.1 to 7.4 for pork.
      The coefficient of variation was lower for sarcomere length than for all other
      traits. Simple correlation coefficients between measurements on raw and cooked
      samples were 0.58 (beef) and 0.11 (pork) for sarcomere length, 0.66 (beef) and
      0.59 (pork) for collagen, and 0.74 (beef) and 0.76 (pork) for desmin degradation.
      Simple correlation coefficients between biochemical traits and measures of
      tenderness (Warner-Bratzler shear force and trained sensory tenderness rating)
      were higher or not different for cooked compared to raw samples. Correlation
      coefficients between biochemical traits and tenderness rating were 0.38 (raw) and
      0.22 (cooked) for sarcomere length, -0.12 (raw) and -0.45 (cooked) for collagen,
      and 0.48 (raw) and 0.80 (cooked) for desmin degradation in beef longissimus and
      0.14 (raw) and 0.15 (cooked) for sarcomere length, -0.38 (raw) and -0.33 (cooked)
      for collagen, and 0.53 (raw) and 0.67 (cooked) for desmin degradation in pork
      longissimus. The coefficients of determination for explaining variation in
      tenderness rating using sarcomere length, collagen concentration, and desmin
      degradation for raw and cooked samples were 0.43 and 0.73 (beef) and 0.48 and
      0.57 (pork), respectively. This study indicates that measurements of biochemical
      traits on the same cooked meat as used for shear force determination account for
      more of the variation in measures of tenderness than biochemical measurements
      made on a separate raw sample.

PMID- 12002336
TI  - Pork quality, processing, and sensory characteristics of dry-cured hams as
      influenced by Duroc crossing and sex.
AB  - This study was designed to evaluate Duroc (DU) crossing for Carso dry-cured ham
      production. One hundred fifty-four pigs (81 females and 73 castrates) of four
      different genotypes, pure Landrace pigs (LAN), offspring of LAN females crossed
      with Large White (LW) males (LWxLAN), offspring of LAN females crossed with DU
      males (DUxLAN), and offspring of LWxLAN females crossed with DU males
      (DUx[LWxLAN]), were chosen in the weight range of 105 to 120 kg (112.7 +/- 0.4
      kg). Raw material quality was evaluated for ham fatness (intra- and intermuscular
      and subcutaneous) and meat quality (pH, color, water-holding capacity) of
      longissimus dorsi, biceps femoris, and semimembranosus muscles. Ham weight losses
      were recorded at different stages of processing. The biceps femoris and
      semimembranosus muscles were analyzed for chemical composition before (lipid,
      moisture, total nitrogen, nonprotein nitrogen) and after (moisture, salt, total
      nitrogen, nonprotein nitrogen) processing. Chemical and sensory analyses were
      performed on 96 dry hams (12 castrates and 12 females per genotype). Biceps
      femoris and semimembranosus muscles were evaluated for color, saltiness, aroma,
      and texture. Pigs of the four genotypes had similar ham fatness as estimated by
      subcutaneous fat thickness. Duroc crosses exhibited higher intramuscular fat
      content, marbling, and intermuscular fat. Crossing with DU resulted in lower
      weight losses during ham processing. Castrates were fatter and had more intra-
      and intermuscular fat and lower ham processing weight losses than females. A
      strong negative relationship between ham fatness and ham processing losses was
      observed. Chemical and sensory traits of dry ham muscles were little affected by
      DU crossing. Lower salt content of biceps femoris was found in DU crosses. Dry
      hams from female pigs had higher total and nonprotein nitrogen, but drier, firmer
      texture and higher resistance to cutting force compared to dry hams from
      castrated pigs. Crossing with DU demonstrated some disadvantages (more
      intermuscular fat, more slice visible fat) and advantages (lower weight loss and
      salt intake) for the quality of dry-cured ham.

PMID- 12002337
TI  - Creatine monohydrate supplementation and the quality of fresh pork in normal and
      halothane carrier pigs.
AB  - The objective of this research was to examine the impact of supplementation with
      creatine monohydrate (CMH) on the quality of various muscles from normal and
      heterozygous halothane carrier pigs. Twenty-nine crossbred pigs, 16 normal (NN)
      and 13 halothane carrier (Nn) genotypes, were supplemented with 0 or 25 g x pig(
      1) x d(-1) of CMH for 5 d before slaughter. Supplemented pigs gained 2.26 kg more
      weight (P < 0.05) during 5 d of supplementation. There were trends (P < 0.10)
      toward higher objective marbling scores and lower cooking loss for supplemented
      pigs. The 45-min pH was 0.27 units higher (P < 0.05) for supplemented pigs in the
      semimembranosus; CMH supplementation did not influence (P > 0.05) drip loss or
      muscle composition. Supplementation with CMH also resulted in lower L* values in
      two ham muscles, semitendinosus (5.15 units) (P < 0.05) and semimembranosus (1.95
      units) (P < 0.10) for Nn carcasses. Genotype had significant effects on most
      quality indicators, with Nn carcasses producing lower-quality lean as evidenced
      by less desirable subjective and objective color and higher drip losses. Genotype
      also affected the composition of several muscles, with the NN carcasses having
      more fat and less moisture.

PMID- 12002338
TI  - HMG-I/Y in human breast cancer cell lines.
AB  - The HMG-I/Y gene encodes the HMG-I and -Y architectural, chromatin binding
      proteins originally identified based on their association with chromosomal DNA.
      HMG-I/Y proteins bind to AT-rich regions in chromosomal DNA and alter gene
      expression. Increased HMG-I/Y protein expression also correlates with neoplastic
      transformation. Previous work from our laboratory has shown that HMG-I/Y is a
      direct c-Myc target gene involved in neoplastic transformation in Burkitt's
      lymphoma. We also observed that HMG-I/Y proteins have several oncogenic
      properties. In this report, we show that HMG-I/Y proteins are increased in
      several human breast cancer cell lines compared to a human breast cell line
      derived from normal breast cells. Decreasing HMG-I/Y proteins using an antisense
      ribozyme approach inhibits transformation in human breast cancer cells,
      suggesting that HMG-I/Y is important for the transformed phenotype observed in
      these cells. In addition, increased expression of the HMG-I isoform in normal
      human breast cells leads to transformation. These results suggest that HMG-I/Y is
      an oncogene important in the pathogenesis of human breast cancer. Although
      additional studies with animal models are needed, the antisense experiments,
      which result in blocking transformation suggest that this approach may have
      therapeutic potential in patients with breast cancer characterized by increased
      HMG-I/Y expression.

PMID- 12002339
TI  - P53 expression is a factor for prognostic assessment in breast sarcoma.
AB  - The present study was undertaken with the aim of evaluating the clinical and
      anatomopathological findings, emphasizing expression of the protein p53 as
      possible prognostic markers, in patients with breast sarcoma. p53
      immunohistochemical expression was determined in archival paraffin embedded
      tissue blocks of 30 breast sarcoma patients, (19 fibrosarcomas, nine malignant
      fibrohistiocytomas and two liposarcomas) treated at the Hospital do Cancer AC
      Camargo, Sao Paulo, Brazil from 1955 to 1990. Immunopositivity was present in 50%
      of the cases. The survival of the patients was compared with the above
      parameters. Median follow up time was 113 months. The 5 years specific survival
      rates were 55.1% for patients with a positive expression of p53 contrariwise to
      92.3% of specific survival found in p53 negative patients (p = 0.04). Positive
      expression of p53 was found in 3/4 (75%) of the patients with local recurrence
      and in 7/9 (77%) of patients with metastatic disease. No significant correlation
      between survival and clinicopathologic features (age, menopausal status, tumor
      size, stage and histological type), was found. A slight positive correlation
      between high grade and poor outcome was observed, 89% of the metastatic cases
      being classified as high grade (p = 0.02, by one sided Fisher's exact test). When
      we have compared, independently, survival probability curves between p53
      positive/negative expression and each category of clinicopathologic features a
      worse prognosis was observed when p53 was positive in patients older than 50
      years (p = 0.01), in tumors larger than 5 cm (p = 0.02), within the malignant
      fibrous histiocytoma subtype (p = 0.01) and in tumors classified as high grade (p
      = 0.07). In conclusion p53 expression seems to be a useful prognostic marker for
      this type of tumor.

PMID- 12002340
TI  - Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica
      granatum) for human breast cancer.
AB  - Fresh organically grown pomegranates (Punica granatum L.) of the Wonderful
      cultivar were processed into three components: fermented juice, aqueous pericarp
      extract and cold-pressed or supercritical CO2-extracted seed oil. Exposure to
      additional solvents yielded polyphenol-rich fractions ('polyphenols') from each
      of the three components. Their actions, and of the crude whole oil and crude
      fermented and unfermented juice concentrate, were assessed in vitro for possible
      chemopreventive or adjuvant therapeutic potential in human breast cancer. The
      ability to effect a blockade of endogenous active estrogen biosynthesis was shown
      by polyphenols from fermented juice, pericarp, and oil, which inhibited aromatase
      activity by 60-80%. Fermented juice and pericarp polyphenols, and whole seed oil,
      inhibited 17-beta-hydroxysteroid dehydrogenase Type 1 from 34 to 79%, at
      concentrations ranging from 100 to 1,000 microg/ml according to seed oil >>
      fermented juice polyphenols > pericarp polyphenols. In a yeast estrogen screen
      (YES) lyophilized fresh pomegranate juice effected a 55% inhibition of the
      estrogenic activity of 17-beta-estradiol; whereas the lyophilized juice by itself
      displayed only minimal estrogenic action. Inhibition of cell lines by fermented
      juice and pericarp polyphenols was according to estrogen-dependent (MCF-7) >>
      estrogen-independent (MB-MDA-231) > normal human breast epithelial cells (MCF
      10A). In both MCF-7 and MB-MDA-231 cells, fermented pomegranate juice polyphenols
      consistently showed about twice the anti-proliferative effect as fresh
      pomegranate juice polyphenols. Pomegranate seed oil effected 90% inhibition of
      proliferation of MCF-7 at 100 microg/ml medium, 75% inhibition of invasion of MCF
      7 across a Matrigel membrane at 10 microg/ml, and 54% apoptosis in MDA-MB-435
      estrogen receptor negative metastatic human breast cancer cells at 50 microg/ml.
      In a murine mammary gland organ culture, fermented juice polyphenols effected 47%
      inhibition of cancerous lesion formation induced by the carcinogen 7,12
      dimethylbenz[a]anthracene (DMBA). The findings suggest that clinical trials to
      further assess chemopreventive and adjuvant therapeutic applications of
      pomegranate in human breast cancer may be warranted.

PMID- 12002341
TI  - Large expansion of morphologically heterogeneous mammary epithelial cells,
      including the luminal phenotype, from human breast tumours.
AB  - Regular expansion of heterogeneous populations of epithelial cells, including the
      luminal phenotype, was achieved from small biopsies of human breast tumours and
      cutaneous metastases by optimized feeder layer technique based on irradiated NIH
      3T3 cells. Forty-one out of 47 primary tumour specimens and all three cutaneous
      metastases grew successfully for two to 10 passages in vitro. The main phenotypes
      of cultured cells and their changes in subcultures were characterized using
      immunocytochemistry and phase contrast microscopy (in few cases also time-lapse
      recording). In the majority of cultured cell populations a fraction of cells
      positive for keratin 19 (K19+), typical for the luminal phenotype, was detected.
      This is the cell type from which breast carcinoma is supposed to arise. While in
      cultures derived from benign lesions only basic phenotypes of luminal and
      myoepithelial cells were found, in cultures derived from malignant tumours
      unusual phenotypes of epithelial cells, in their majority K19+, were detected.
      The growth properties of cells from six benign and seven malignant samples were
      analyzed in detail. In the analyzed cell populations the culture lifetime -
      related to the number of colony-forming cells varied for cells from malignant
      tumours between 21 and 51 and from benign tumours between 22 and 40 cell
      generations. The total number of passages achieved was three to seven for
      malignant or four to nine for benign cultures. In spite of negative results of
      tumourigenicity testing in immunologically compromised Nu/nu mice the potential
      to culture apparently neoplastic cells was indicated by positive immunostaining
      for the p53 oncoprotein (seven of 23 tested malignant cases), the src oncoprotein
      (five of eight), and overexpression of the c-erbB-2 protein (five of 26). This
      was further confirmed by successful cultivation of malignant cells from cutaneous
      metastases. Two of the three metastasis-derived cultures were nearly
      homogeneously positive for K19 while the third was almost negative. The results
      proved the optimized feeder layer technique to be useful for regular yielding of
      large amounts of epithelial cells from small tumour biopsies and for supporting
      the majority of cell phenotypes present in the original tumour. Therefore, it
      appeared to be a promising tool for further analysis of interactions between
      luminal and myoepithelial cells in the development of human breast carcinoma and
      for the study of individual tumours.

PMID- 12002342
TI  - Multidrug-resistant MCF-7 breast cancer cells contain deficient intracellular
      calcium pools.
AB  - Emergence of resistance to antineoplastic drugs poses a major impediment to the
      successful treatment of breast cancer. We previously reported that human breast
      carcinoma MCF-7 cells selected for resistance against doxorubicin (MCF-7/DOX
      cells) expressed high levels of tissue-type transglutaminase (tTGase), a calcium
      dependent protein cross-linking enzyme that plays a role in apoptosis. The
      purpose of this study was to determine the mechanisms by which MCF-7/DOX cells
      survive and proliferate despite high levels of tTGase expression. Our results
      demonstrate that the MCF-7/DOX cells contain deficient intracellular calcium
      pools, which may explain their ability to survive and tolerate the high levels of
      tTGase expression. Treatment with thapsigargin failed to induce any significant
      killing of MCF-7/DOX cells. Similar treatment of the drug-sensitive MCF-7 wild
      type (MCF-7/WT) cells, however, induced significant apoptosis. Treatment with the
      ionophore A23187, on the other hand, killed a large percentage of both the MCF
      7/DOX and the MCF-7/WT cells. We also established a revertant cell line, MCF
      7/RT, from MCF-7/DOX cells to rule out the involvement of P-glycoprotein (P-gp)
      in these phenomena. Unlike the MCF-7/DOX cells, the MCF-7/RT cells showed no
      detectable P-gp expression; the MCF-7/RT cells, however, continued to express
      high levels of tTGase. Moreover, like MCF-7/DOX cells, the MCF-7/RT cells were
      highly resistant to thapsigargin-induced apoptosis but were sensitive to the
      ionophore A23187-induced apoptosis. These results suggest that the resistance of
      MCF7/DOX cells to thapsigargin is linked to their defective intracellular Ca2+
      stores, a notion that was directly confirmed by single-cell spectrofluorometric
      analysis.

PMID- 12002343
TI  - Expression of estrogen receptor beta isoforms in human breast cancer tissues and
      cell lines.
AB  - Estrogen receptor alpha (ER-alpha) is an important regulator of growth and
      differentiation in the mammary gland and the female reproductive tract. It is
      also involved in the development of malignant tumors. The human ER-beta is highly
      homologous to the extensively studied human ER-alpha. It binds to the endogenous
      17beta-estradiol with similar affinity as ER-alpha and the transcriptional
      activity through the consensus ERE can be stimulated. Five ER-beta isoforms were
      cloned and characterized. They diverge at a common position within the predicted
      helix 10 of the ligand-binding domain of the human ER-beta, with nucleotide
      sequences consistent with different exon usage. These isoforms of human ER-beta
      show differential expression in tissues and in tumor cell lines. Furthermore,
      they are predicted to form DNA-binding heterodimers when coexpressed. Expression
      of some of the ER-beta isoforms in human breast tissue, breast cancer, and breast
      cancer cell lines were reported by several groups. However, there is no complete
      analysis of the gene expression pattern of all ER-beta isoforms in breast cancer
      so far. In this study, we examined the mRNA expression of each of the ER-beta
      isoforms in 30 tumors from breast cancer patients and 21 breast cell lines. In
      conclusion, expression of ER-beta1, ER-beta2, and ER-beta5 were observed in
      different cell lines as well as in the tumors, ER-beta4 isoform was expressed in
      all samples, and ER-beta3 isoform was not detected in any of the samples
      examined. There were no associations of the expression of all ER-beta isoforms
      with the invasiveness of the cell lines as well as with clinical parameters of
      the tumors.

PMID- 12002344
TI  - Distinct mechanisms of bisphosphonate action between osteoblasts and breast
      cancer cells: identity of a potent new bisphosphonate analogue.
AB  - While the effects of bisphosphonates on bone-resorbing osteoclasts have been well
      documented, the effects of bisphosphonates on other cell types are not as well
      studied. Recently, we reported that bisphosphonates have direct effects on bone
      forming human fetal osteoblast cells (hFOB). In this report, the role of the
      mevalonate pathway in the actions of bisphosphonates on hFOB, and MDA-MB-231
      human breast cancer cells was examined. These studies included a novel
      bisphosphonate analog, the anhydride formed between arabinocytidine 5' phosphate
      and etidronate (Ara-CBP). Ara-CBP was the most potent inhibitor of hFOB and MDA
      MB-231 cell proliferation, and stimulator of hFOB cell mineralization compared to
      etidronate, the anhydride formed between AMP and etidronate (ABP), pamidronate,
      and zoledronate. Inhibition of hFOB cell proliferation by Ara-CBP and zoledronate
      was partially reversed by mevalonate pathway intermediates, and stimulation of
      hFOB cell mineralization was completely reversed by mevalonate pathway
      intermediates. These results suggest that zoledronate and Ara-CBP act, at least
      in part, via inhibition of the mevalonate pathway in hFOB cells. In contrast,
      none of the mevalonate pathway intermediates reversed the inhibition of MDA-MB
      231 cell proliferation by the bisphosphonates, or the effects of pamidronate on
      hFOB cells. As a positive control, the effects of mevastatin on hFOB and MDA-MB
      231 cells were completely reversed by mevalonate. In summary, these data suggest
      that zoledronate and Ara-CBP induce human osteoblast differentiation via
      inhibition of the mevalonate pathway. In contrast, the inhibition of MDA-MB-231
      cell proliferation by the bisphosphonates appears to be through mechanisms other
      than inhibition of the mevalonate pathway.

PMID- 12002345
TI  - Normal breast epithelial cells induce p53-dependent apoptosis and p53-independent
      cell cycle arrest of breast cancer cells.
AB  - Cancer development depends not only on the nature of cancerous cells themselves,
      but also on the regulatory effects of various normal cells. The present study was
      performed to investigate the effect of normal breast epithelial cells (NBEC) on
      the growth of breast cancer cells under various conditions. We demonstrated that
      NBEC-conditioned medium (NBEC-CM) inhibited growth of breast cancer cell lines in
      monolayer culture and three-dimensional collagen gel culture, as well as in soft
      agar. In MCF-7 and T-47D cells which have a functional p53, NBEC-CM induced
      apoptosis without modifying cell cycle progression. In MDA-MB-231 and BT-20 cells
      that have a non-functional p53, NBEC-CM did not induce apoptosis, although a
      slight G1 blokage was observed in MDA-MB-231 cells. Transient transfections of
      MCF-7 and T-47D cells demonstrated that NBEC-triggered apoptosis was mediated by
      endogenous p53. Moreover, pifithrin-alpha which specifically inhibits the
      transcriptional activity of p53, completely abolished NBEC-induced apoptosis in
      both MCF-7 and T-47D cells, indicating that p53 mediated apoptosis via its
      transcriptional activity. Finally, orthovanadate, a protein tyrosine phosphatase
      inhibitor, completely inhibited NBEC-triggered apoptosis, indicating that NBEC
      triggered apoptosis was regulated by tyrosine phosphatases.

PMID- 12002346
TI  - Conductivities of three-layer live human skull.
AB  - Electrical conductivities of compact, spongiosum, and bulk layers of the live
      human skull were determined at varying frequencies and electric fields at room
      temperature using the four-electrode method. Current, at higher densities that
      occur in human cranium, was applied and withdrawn over the top and bottom
      surfaces of each sample and potential drop across different layers was measured.
      We used a model that considers variations in skull thicknesses to determine the
      conductivity of the tri-layer skull and its individual anatomical structures. The
      results indicate that the conductivities of the spongiform (16.2-41.1 milliS/m),
      the top compact (5.4-7.2 milliS/m) and lower compact (2.8-10.2 milliS/m) layers
      of the skull have significantly different and inhomogeneous conductivities. The
      conductivities of the skull layers are frequency dependent in the 10-90 Hz region
      and are non-ohmic in the 0.45-2.07 A/m2 region. These current densities are much
      higher than those occurring in human brain.

PMID- 12002347
TI  - Early components of event-related potentials related to semantic and syntactic
      processes in the Japanese language.
AB  - Brain activities were compared between semantic and syntactic processing in the
      Japanese language using event-related potentials with a 58-ch EEG system. We
      previously found that semantic violations elicited N400 and syntactic violations
      elicited P600 but not early left anterior negativity (ELAN) or left anterior
      negativity (LAN) using a relatively long stimulus presentation time (1 s). In the
      present study, we adopted a shorter stimulus presentation time (0.5 s), which
      might impose a heavier burden on the working memory system, to test the possible
      relevance of load on the working memory system to ELAN/LAN. A global field power
      analysis showed an increased potential field strength at the latency of 320 ms in
      either type, as well as those at the later latencies reflecting N400 (556 ms) and
      P600 (712 ms). Statistical analyses revealed a significant negative deflection in
      the right frontal region for the semantic type, whereas no significant deflection
      in either specified region was obtained for the syntactic type at the latency of
      320 ms. The lack of ELAN/LAN suggested that it was not due to the deactivation of
      the working memory system. Moreover, scalp current density topographies implied
      that the processing of the verbal stimuli was mediated by distinct areas within
      the left temporal region, according to its semantic congruency with the preceding
      context at a latency as early as 320 ms. These findings are in line with the dual
      route hypothesis of reading, which suggests that the reading of verbal stimuli
      semantically incongruent with the preceding context is dominated by phonological
      processes rather than lexico-semantic.

PMID- 12002348
TI  - Reproducibility and stability of neuroelectric source imaging in primary
      somatosensory cortex.
AB  - The present study investigated the test-retest reliability of EEG source
      localization of somatosensory evoked potentials (SEPs) over an extended time
      period and tested the accuracy of source reconstruction co-registred with
      individual brain morphology (MRIs). Seven healthy subjects were stimulated
      pneumatically at the first digit and fifth digit of each hand and at the left and
      right lower corner of the mouth in two sessions spaced several weeks apart. At
      each location 1000 stimuli were presented. The overlay of the dipole
      localizations with the individual anatomic structure of the subjects' cortex was
      accomplished by the use of magnetic resonance images. A spherical 4-shell model
      of the head was used to localize the neuroelectric sources of the EEG data. In
      two cases a more realistically shaped 3 compartment model was computed using the
      boundary element method (BEM). The source localizations of the SEP component were
      found to be highly reproducible: the mean standard deviation of the dipole
      locations was 5.21 mm in the x-, 5.98 mm in the y- and 4.22 mm in the z
      direction. BEM was not found to be superior to a 4-shell model. These data
      support the use of multi-electrode EEG recordings combined with MRI as an
      adequate method for the investigation of the functional organization of the
      somatosensory cortex.

PMID- 12002349
TI  - Modulation of gamma-band spectral power by cognitive task complexity.
AB  - This study evaluated the utility of electroencephalographic (EEG) measures as
      indices of regional cerebral activation during performance of visuo-semantic
      analysis tasks in neurologically intact adult volunteers. EEG was recorded from
      28 scalp locations as participants performed three visual discrimination tasks
      designed to tap into increasingly more complex operations regularly involved in
      the recognition of living animate objects. In addition, data from a control task
      involving the same stimuli, but requiring no cognitive decision or response, was
      included. EEG records were quantified using power spectrum measures in five
      frequency bands (delta, theta, alpha, beta, and gamma). Results showed a
      significant linear increase in absolute power in the gamma band with increasing
      task complexity over left hemisphere frontal and occipital regions, and over
      right temporoparietal regions.

PMID- 12002350
TI  - Dynamics of brain activation during an explicit word and image recognition task:
      an electrophysiological study.
AB  - Recent brain imaging studies suggest that semantic processing of words and images
      may share a common neural network, although modality-specific activation can also
      be observed. Other studies using event-related potentials (ERPs) report that
      brain responses to words and images may already differ at approximately 150 ms
      following stimulus presentation. The question thus remains, which differences are
      due to perceptual categorization processes and which differences are due to the
      semantic ones? Using ERP recordings and spatio-temporal source localization
      analysis, we investigated the dynamics of brain activation during a recognition
      task. The stimuli consisted of a randomized set of verbal (words vs. non-words)
      and pictorial items (line drawings of objects vs. scrambled drawings). After each
      stimulus, subjects had to decide whether it corresponds to a recognizable word or
      objects. ERP map series were first analyzed in terms of segments of quasi-stable
      map topography using a cluster analysis. This showed that verbal and pictorial
      stimuli elicited different field patterns in two time segments between
      approximately 190-400 ms. Before and after this period, map patterns were similar
      between verbal and pictorial conditions indicating that the same brain structures
      were engaged during the early and late steps of processing. Source localization
      analysis of map segments corresponding to the P100 and the N150 components first
      showed activation of posterior bilateral regions and then of left temporo
      posterior areas. During the period differentiating conditions, other patterns of
      activation, involving mainly left anterior and posterior regions for words and
      bilateral posterior regions for images, were observed. These findings suggest
      that, while sharing an initial common network, recognition of verbal and
      pictorial stimuli subsequently engage different brain regions during time periods
      generally allocated to the semantic processing of stimuli.

PMID- 12002351
TI  - Microsurgical replantation of sexual organs in three patients.
AB  - OBJECTIVE: The present study deals with microsurgical replantation technique.
      MATERIAL AND METHODS: The technique was applied in 3 patients whose sexual organs
      had been accidentally cut off. RESULTS: Necrosis of the sutured organs occurred
      in 2 cases. In 1 case, however, healing with proper miction and sexual function
      was achieved. Prolonged period (over 12 hours) from the accident to operation as
      well as the extensive injury of tissues with the vascular system crush were
      considered to be the main reason for failure. CONCLUSIONS: Microsurgical
      reconstruction of penis and testes with the use of vessel grafts prolonged the
      hypoxia which led to necrosis. Disturbances in vein blood outflow from the
      sutured organs contributed to this process as well. The third case resulted in
      success mostly due to quick intervention (5 h from injury) as well as to proper
      microsurgical reconstruction of vessels, nerves, and urethra. In addition
      suprapubic urine diversion was successfully applied and the urethra healed on the
      perforated catheter. Routine antibiotics as well as antithrombotic prophylactics
      were administered in all of the 3 cases.

PMID- 12002352
TI  - Pharmacokinetics, efficacy, and safety of intravesical formulation of oxybutynin
      in patients with detrusor overactivity.
AB  - OBJECTIVE: To determine the pharmacokinetics of oxybutynin and its main active
      metabolite, N-desethyloxybutynin, after multiple dosage (5 mg/30 ml three times
      daily) of intravesical oxybutynin formulation. Furthermore, to determine the
      efficacy and safety of intravesical oxybutynin in the symptomatic relief of urge
      incontinence or urgency in adult patients with detrusor hyperreflexia or
      instability. MATERIAL AND METHODS: Nine patients were randomly allocated to
      treatment with a special bladder instillation formulation of oxybutynin or
      placebo for two 14-day treatment periods in a double-blind, cross-over manner.
      The third, open study period was designed for pharmacokinetic purposes with all
      patients on the active drug. The pharmacokinetics was depicted by AUC0-24, Cmax,
      Cmin, and t(max), The efficacy was evaluated from the data collected from urinary
      voiding diaries and cystometries. The safety was measured by recording adverse
      events on questionnaires. Patients who were willing to continue with the
      intravesical oxybutynin treatment entered the 1-year extension part of the study.
      RESULTS: Oxybutynin was absorbed from the bladder with a geometric mean Cmax of
      9.4 ng/ml and AUC0-24 of 92 ng x h/ml. For N-desethyloxybutynin, the geometric
      mean Cmax was 14.4 ng/ml and AUC0-24 186 ng x h/ml. Elimination of the drug was
      protracted, as there were detectable serum concentrations of both oxybutynin and
      N-desethyloxybutynin even 24 hours post-dose. The mean number of toilet
      visits/day decreased from the baseline value of 6.9 to 5.7 during oxybutynin
      treatment, whereas during the placebo period the value increased to 7.4 (p =
      0.022). It remained at the same decreased level during the one-year follow-up
      period. CONCLUSIONS: Oxybutynin is readily absorbed from the bladder after
      intravesical administration. The serum concentrations of oxybutynin after single
      5 mg intravesical doses are at least as high as those reported after oral drug
      intake, but the parent drug/metabolite ratio is much higher after intravesical
      administration. The elimination of oxybutynin as well as its metabolite is
      prolonged after intravesical administration compared with that reported after
      oral drug intake. The mean number of daily toilet visits decreased significantly
      in the oxybutynin group.

PMID- 12002353
TI  - The effect of acute bladder filling on plasmatic antidiuretic hormone production
      in healthy adult volunteers.
AB  - OBJECTIVE: To assess the existence of a vesical hypothalamic reflex by evaluating
      the changes of plasmatic ADH levels during acute bladder filling in healthy adult
      volunteers. MATERIALS AND METHODS: Twenty normal male subjects aged between 19
      and 40 years (average age 31.6 years) were evaluated. All subjects signed
      informed consent. The subjects had no pathologic blood and urine examination, no
      cardiovascular, hepatic, renal disease, they were no smokers and they did not
      take drugs which may interfere with plasmatic ADH levels. A blood sampling at
      rest condition (time 0) and successively during cystometry in the presence of
      first sensation, normal and strong desire was carried out. Plasmatic ADH was
      measured on extracted samples by radioimmunoassay. A one-factor repeated measures
      analysis of variance was employed to verify the effect of time on ADH levels. The
      Greenhouse-Geisser and Huynh-Feldt adjustments were adopted to protect against
      the case of violation of homogeneity of covariance. RESULTS: Statistical analysis
      did not show significant differences of plasmatic ADH levels between rest
      condition and bladder filling. CONCLUSIONS: We exclude the existence of a vesical
      hypothalamic reflex and we suppose that extravesical factors may interfere with
      the plasmatic ADH production during the night.

PMID- 12002354
TI  - Treatment of patients with clinical T3 prostate cancer.
AB  - OBJECTIVE: To describe and evaluate treatment alternatives for patients with
      clinical T3 prostate cancer. MATERIAL AND METHODS: Literature review with main
      focus on recent studies in order to include the impact of prostate specific
      antigen (PSA). The possibility of using neoadjuvant/adjuvant hormonal therapy in
      combination with surgery or radiation was assessed. Results were related to life
      expectancy, tumour grade and serum PSA. RESULTS: M and N-staging is mandatory
      before treatment with curative intent. Watchful waiting is an option for selected
      patients but early hormonal therapy seems to offer some survival advantages.
      Standard 65-70Gy external beam radiation is not sufficient for these patients
      with extracapsular disease but better results are obtained with dose-escalation
      (beyond 70Gy) and/or adjuvant hormonal therapy. Radical prostatectomy may be an
      option for patients with long life expectancy and "early" tumours, neoadjuvant
      hormonal withdrawal is of no proven value. CONCLUSIONS: Patients with a long life
      expectancy should not be denied treatment with curative intent solely based on
      the finding of extracapsular disease.

PMID- 12002355
TI  - Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate
      cancer (AIPC)--delayed response and flare phenomenon should be considered.
AB  - BACKGROUND: Compared with the native drug, liposomal PEG-coated doxorubicin
      (Caelyx) enhances tumour activity and reduces toxicity. The formulation may
      therefore be beneficial in anthracycline-sensitive malignancies, where toxicity
      represents a major problem, as is the case in androgen-insensitive prostate
      cancer (AIPC). METHODS: In a multi-centre design 28 patients with advanced AIPC
      received Caelyx 40 mg/m2 as a 1-hour infusion every month. PSA-based biochemical
      and subjective response was recorded. RESULTS: Three patients had biochemical
      responses, a subjective response was recorded in a fourth patient. No Grade 4
      toxicity was encountered. Three patients developed a spontaneously recovering
      plantar-palmar erythema. In 3 of the 4 responding patients, the nadir PSA value
      was noted after 12 and 16 weeks, respectively. A possible flare phenomenon for
      PSA was evident in 4 patients. CONCLUSION: Caelyx has limited activity in
      advanced AIPC. Due to its low toxicity profile the drug may be a worthwhile
      component of combination treatment of this chemotherapy-resistant condition. In
      general, clinicians should be aware of possible delay in PSA response as well as
      possible flare phenomenon during investigational systemic treatment of AIPC.
      Furthermore, standardization of blood sampling and PSA analyses are necessary in
      future therapeutic trials of AIPC.

PMID- 12002356
TI  - Health-related quality of life after 5-12 years of continent ileal urostomy (Kock
      reservoir) in children and adolescents.
AB  - OBJECTIVE: To assess quality of life after continent ileal reservoir diversion in
      children and adolescents. MATERIAL AND METHODS: Nine boys and 9 girls (10.8-18
      years old at surgery) were operated with a Kock reservoir and followed for 5-12
      years. They participated in an interview using a questionnaire based on the
      Swedish self-esteem inventory, "I think I am". The questionnaire consisted of 76
      questions that covered medical, physical, psychological, social, body image and
      sexual aspects. RESULTS: Six of 18 patients had some difficulties on
      catheterization. Five complained of pain or bleeding during evacuation. Two
      patients had slight urinary leakage between evacuations and 6 had mucus
      secretion. Ten patients had diarrhea with different frequencies. Physical
      activities were not hampered by the operation in any patient. Instead, activities
      such as full day outside home, friend at home overnight, using all types of
      clothes, and participation in camps were increased in 8, 6, 5 and 5 patients,
      respectively. All patients but 2 had an excellent relation with friends and
      family members. More than half of patients had excellent positive self-esteem and
      body image and the rest had very good self-esteem. However, some patients were
      concerned about how they looked and felt that life was unfair to them.
      CONCLUSIONS: The patients were satisfied with their operation. They were
      physically active and declared a positive perspective regarding self-esteem and
      body image. The medical problems related to the operation did not have any
      negative influence on the self-esteem or body image. The choice of the operation
      can only be determined on the basis of an attentive dialogue between surgeon,
      child and parents.

PMID- 12002357
TI  - DNA ploidy and S-phase fraction as predictive factors of response and outcome
      following neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (M-VEC)
      chemotherapy for invasive bladder cancer.
AB  - OBJECTIVE: To investigate the value of DNA ploidy and S-phase fraction (SPF) as
      factors that could predict response and outcome of invasive transitional cell
      carcinoma (TCC) of the bladder to neoadjuvant methotrexate, vinblastine,
      epirubicin and cisplatin (MVEC) chemotherapy. MATERIALS AND METHODS: Twenty-four
      patients with localized invasive TCC of the bladder (stages T3 to T4a, NoMo) were
      treated with neoadjuvant MVEC chemotherapy. DNA flow cytometry was performed in
      paraffin-embedded tissue obtained by transurethral resection before chemotherapy.
      Radical cystectomy specimens were utilized for complete pathologic staging. The
      tumors were subdivided into high- and low-SPF tumors according to their SPF
      value. DNA ploidy status was evaluated into two groups (diploidy and
      nondiploidy). RESULTS: DNA ploidy was not correlated to the response to
      chemotherapy (p = 0.67), and overall or disease-free survival (p = 0.27 and p =
      0.69, respectively). Major response (pathologic complete response and partial
      response) was more often found in the high SPF group than among tumors with low
      SPF (p = 0.02). High SPF tumors were significantly associated with increased
      overall and disease-free survival (p = 0.0056 and p = 0.0059, respectively).
      CONCLUSION: A high SPF, but not DNA ploidy, may be helpful to identify patient
      likely to respond and survive longer following neoadjuvant MVEC chemotherapy in
      the treatment of invasive bladder cancer.

PMID- 12002358
TI  - Effects of fluid and dobutamine treatment on renal function during partial
      superior mesenteric artery occlusion and reperfusion.
AB  - OBJECTIVE: We compared the effects of dobutamine, fluid resuscitation and their
      combination on renal function during experimental intestinal ischaemia and
      reperfusion. MATERIALS AND METHODS: Superior mesenteric artery (SMA) blood flow
      was reduced to 30% from the baseline for 120 minutes in 24 anaesthetized pigs
      (ischaemic group); 24 pigs (sham group) served as non-ischaemic controls. The
      animals were further assigned into four treatment arms. In the control arms, the
      animals were given only basic fluid therapy. In the fluid therapy arms, pulmonary
      capillary wedge pressure (PCWP) was maintained at 10 mmHg with intravenous
      fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at
      a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arms,
      dobutamine at 10 microg/min/kg was given and PCWP was maintained at 10 mmHg with
      fluids. At 120 minutes, the occluder was released in all study groups and the
      animals were followed for an additional 60 minutes. Renal function was evaluated
      by means of serum and urine creatinine. urine volume and creatinine clearance.
      Systemic and regional haemodynamics as well as intramucosal pH, intramucosal
      arterial pCO2 gradient, and portal venous-arterial lactate gradient were
      measured. RESULTS: In the ischaemic groups, diuresis increased and serum and
      urine creatinine decreased significantly in fluid (p < 0.01, p < 0.01 and p <
      0.05, respectively) and dobutamine-fluid (p < 0.01, p < 0.001 and p < 0.001,
      respectively) treated groups during SMA ischaemia. After SMA reperfusion,
      diuresis decreased in control group (p < 0.05) and in animals treated with
      dobutamine alone (p < 0.01). In addition, urine creatinine increased in
      dobutamine treated group (p < 0.05), and creatinine clearance decreased in
      control group (p < 0.01). Renal function and diuresis during the SMA occlusion
      and reperfusion did not differ between ischaemic and sham groups. All fluid
      treated groups had lower serum creatinine during SMA occlusion than control
      groups (p < 0.001). CONCLUSIONS: Intestinal ischaemia caused by partial SMA
      occlusion did not influence renal function. On the contrary, SMA reperfusion
      resulted in a significant impairment of renal function both in ischaemic and sham
      operated animals. The impairment was most obvious in control groups and in
      animals treated with dobutamine alone.

PMID- 12002359
TI  - Long term follow-up of superficial invasive bladder carcinoma with or without
      concomitant epithelial atypia--recurrence and progression.
AB  - OBJECTIVE: To examine the significance of concomitant epithelial atypia on late
      recurrence and progression by long-term follow-up of superficial invasive bladder
      tumours (stage T1). MATERIAL AND METHODS: Seventy consecutive, unselected
      patients with newly diagnosed transurethral resection (TURB)-treated stage T1
      bladder tumour, and at least 1 year progression-free survival. Preselected site
      biopsies (PSB) were obtained prospectively to evaluate the significance of
      concomitant urothelial atypia. Followed for up to 17.6 years. RESULTS: The
      cumulative probability of recurrence (overall) was 85%, and for new stage T1
      tumour 70% after 10 years. Forty per cent of those who survived 5 years without
      recurrence, were readmitted with often invasive recurrence later. Positive PSB
      significantly (p < 0.0001) predicted new T1 tumour. Progression (T2+ or
      metastases) occurred in 27 cases (39%) after the first year. The cumulative
      probability was 60% (15 years), with a mean progression-free interval of 64
      months. Positive PSB, size >3 cm and early recurrence were significant predictive
      factors in multivariate analysis. CONCLUSION: T1-tumours are at high risk for
      late invasive recurrence and progression, especially if associated with
      urothelial atypia elsewhere in the bladder.

PMID- 12002360
TI  - Repeated transurethral resection of recurrent superficial bladder tumors--does it
      affect the spread and stage of the tumor?
AB  - OBJECTIVES: This prospective study was done to demonstrate the effect of repeated
      resection of superficial bladder tumors (TURT) on deep malignant cell
      infiltration in bladder wall. MATERIAL AND METHODS: Thirty-six patients underwent
      radical cystectomy for invasive bladder cancer, 16 patients originally had
      superficial cancer that became invasive after repeated TURT (group I) and the
      other 20 patients (group II) presented with invasive bladder cancer from the
      start. Each cystectomy specimen was subjected to a thorough histopathological
      study. RESULTS: There was a statistically significant difference in pattern of
      local spread of malignant cells between the two groups. Isolated clusters of
      malignant cells in-between normal bladder muscle fibers, isolated subserosal
      malignant deposits as well as cells reaching the adjacent cervix uteri were found
      only in group I. Intravesical pressure was measured in another 10 patients during
      TURT and was found to be high reaching up to 80 cm H2O. CONCLUSIONS: We conclude
      that some malignant cells penetrate through the denuded urothelium during TURT by
      the effect of high intravesical pressure. This may be responsible, among other
      factors, for tumor recurrence with deeper stages.

PMID- 12002361
TI  - Pentoxifylline attenuates reperfusion injury in testicular torsion.
AB  - OBJECTIVES: An experimental study was designed to evaluate the effects of
      pentoxifylline (Ptx) on lipid peroxidation, and histopathology in both testes
      after unilateral testicular torsion and detorsion. MATERIALS AND METHODS: Forty
      adult male albino Wistar rats were randomly divided into 4 groups of sham
      operation, sham operation with Ptx, torsion and detorsion, torsion and detorsion
      with Ptx. After intraperitoneal administration of Ptx at a dose of 50 mg/kg 15
      min before torsion; right testes of the rats underwent 30 min of torsion and 30
      min of detorsion. Malondialdehyde (MDA) levels were assayed and histopathological
      changes were evaluated in both testes of all groups. RESULTS: Unilateral
      testicular torsion and detorsion caused an increase in the MDA levels of both
      testes. Histopathological evaluation showed interstitial hemorrhage on the
      ipsilateral side. Pentoxifylline decreased MDA levels on both side, and
      attenuated interstitial injury on the ipsilateral side. CONCLUSIONS: The results
      of this study suggest that pentoxifylline treatment attenuates reperfusion damage
      on both side, possibly with its effects on blood flow and neutrophils. However,
      further studies are necessary to evaluate the effects of pentoxifylline on
      testicular torsion.

PMID- 12002362
TI  - Adrenal tumor with caval extension--case report and review of the literature.
AB  - Extension of adrenal cortical carcinomas into the IVC is rare. We describe one
      such tumor that extended to the level of the right atrium. In an effort to aid
      recognition and guide work-up of an upper pole lesion, we review the literature
      comprised of 77 similar cases and analyze the data in terms of patient
      demographics, anatomic distribution, clinical and laboratory evidence of
      endocrine function. Our review suggests that over half of all adrenal lesions
      with IVC extension will be clinically nonfunctional, including up to 17% of
      pheochromocytomas.

PMID- 12002363
TI  - Xanthogranulomatous pyelonephritis--the "great imitator" justifies its name.
AB  - A case of focal xanthogranulomatous pyelonephritis (XGP) clearly imitating renal
      tumour is presented. The authors underline the need to include focal XGP in the
      preoperative differential diagnosis of a renal mass even in the absence of
      typical characteristics.

PMID- 12002364
TI  - Primary malignant melanoma of the kidney.
AB  - The fourth patient with a solitary malignant melanoma of the kidney with no
      apparent primary lesion or metastasis is reported.

PMID- 12002365
TI  - Endovascular approach to treating secondary arterioureteral fistula.
AB  - Two patients with the rare entity of arterio-ureteral fistula are presented. Both
      highlight the predisposing factors of radiation, major surgery in the region,
      history of vascular surgery and presence of double-J-stent. Both patients
      presented with the clinical sign of intermittent gross hematuria. Both patients
      were successfully treated by endovascular intervention using graft covered stent.

PMID- 12002366
TI  - Acquired cystic kidney disease following long-term peritoneal dialysis for
      congenital nephrotic syndrome.
AB  - We describe here the clinicopathological findings in a child with congenital
      nephrotic syndrome (CNS) non-responsive to medical therapy who developed acquired
      cystic kidney disease (ACKD) in both native kidneys after long-term peritoneal
      dialysis. This case indicates that CNS is a further pathologic condition related
      to the development of ACKD.

PMID- 12002367
TI  - Ureteric obstruction caused by pelvic actinomycosis.
AB  - Ureteric obstruction is a well-known complication of actinomycosis, however its
      management in previous case reports has been very variable and sometimes
      mutilating. We report a rare case presenting with ischiorectal abscess that was
      successfully treated by JJ stenting and penicillin.

PMID- 12002368
TI  - An unusual complication of penile prosthesis following urethroplasty.
AB  - We report a case of an adult who had undergone transpubic urethroplasty for a 5
      cm long posterior urethral stricture. A malleable penile prosthesis (AMS 600R)
      was implanted 19 months later for the trauma-related impotence. The patient was
      discovered to develop a complete obliteration of the urethra after removal of
      infected penile prosthesis 18 months later. Perineal urethroplasty cured his
      restricture. Suggestions are made to prevent urethral restricture if penile
      prosthesis is required after urethroplasty.

PMID- 12002369
TI  - Risperidone-induced priapism.
AB  - Priapism is well documented as a potential side effect of psychotropic
      medications. To date, there have been no reports of risperidone-induced priapism
      in the urologic literature. We report a case of risperidone-induced priapism
      requiring surgical treatment.

PMID- 12002370
TI  - Dynamic performance of the mechanism of an automatically deployable ROPS.
AB  - The mechanism for an automatically deployable ROPS (AutoROPS) has been designed
      and tested. This mechanism is part of an innovative project to provide passive
      protection against rollover fatality to operators of new tractors used in both
      low-clearance and unrestricted-clearance tasks. The device is a spring-action,
      telescoping structure that releases on signal to pyrotechnic squibs that actuate
      release pins. Upper post motion begins when the release pins clear an internal
      piston. The structure extends until the piston impacts an elastomeric ring and
      latches at the top position. In lab tests the two-post structure consistently
      deployed in less than 0.3 s and latched securely. Static load tests of the
      telescoping structure and field upset tests of the fully functional AutoROPS have
      been successfully completed.

PMID- 12002371
TI  - Static load test performance of a telescoping structure for an automatically
      deployable ROPS.
AB  - The automatically deployable ROPS was developed as part of an innovative project
      to provide passive protection against overturn fatality to operators of new
      tractors used in both low-clearance and unrestricted-clearance tasks. The primary
      objective of this phase of the research was to build a telescoping structure that
      would prove that a ROPS can be built that will (1) reliably deploy on signal, (2)
      rise in a sufficiently short amount of time, (3) firmly latch in its deployed
      position, and (4) satisfy SAE J2194 testing requirements. The two-post structure
      had previously been found to meet deployment time criteria, and design analyses
      indicated that neither the slip-fit joint nor the latch pins would fail at test
      loading. Four directions of static loading were applied to the structure to
      satisfy SAE requirements. For the series of static loading tests, the raised
      structure was found to maintain a protective clearance zone after all loads were
      applied. The structure is overly stiff and should be redesigned to increase its
      ability to absorb ground-impact energy. Results of dynamic tests and field upset
      tests are reported in companion articles. The next phase of development is to
      optimize the structure so that it will plastically deform and absorb energy that
      would otherwise be transferred to the tractor chassis.

PMID- 12002372
TI  - Women in agriculture: risks for occupational injury within the context of
      gendered role.
AB  - Women continue to make significant contributions to farming. Not only do women
      participate in the traditional roles of homemaker, caregiver, and wife, they also
      work side-by-side with their spouses in keeping the farm viable. More daughters
      are entering the farming business, either as partners with other family members
      or as independent operators. Each year since the United States Department of
      Agriculture began including gender in the Census of Agriculture, the percentage
      of women engaged in agriculture has increased, and women's participation in
      agriculture is increasing faster than in other business segments. This article
      examines the role of women in agriculture and how sociocultural, economic, and
      physical factors may affect women's exposure to injury-producing events and their
      knowledge and beliefs about injury prevention. To date, few studies have examined
      work-related unintentional injuries among farm women. Even less is known about
      the extent to which occupational risks are recognized when women seek medical
      care. Differences in size and stature, increased physical strain, and low maximal
      oxygen uptake may predispose women to ergonomic-related injuries. Limitations of
      current research and recommendations for future analyses are discussed.

PMID- 12002373
TI  - Tienes leche? The changing demographics of the dairy workforce.

PMID- 12002374
TI  - Traumatic injuries in agriculture.
AB  - The National Coalition for Agricultural Safety and Health (NCASH) in 1988
      addressed issues in agriculture and noted "a sense of urgency... arose from the
      recognition of the unabating epidemic of traumatic death and injury in American
      farming . . ." This article provides an update to the NCASH conference on
      traumatic injuries in agriculture, a history on how the facts and figures were
      arrived at for the NCASH conference, and a current report on the status of
      traumatic injuries in agriculture in the U.S. Fatal and nonfatal injuries are
      addressed along with national and regional surveillance systems. The Census of
      Fatal Occupational Injuries (CFOI) was used for reporting national agricultural
      production fatal injuries from 1992-1998 (25.8 deaths per 100,000 workers), the
      Traumatic Injury Surveillance of Farmers (TISF) 1993-1995 was used to report
      nonfatal injuries occurring nationally (7.5/100 workers), and Regional Rural
      Injury Studies I and II (RRIS-I and RRIS-II) were used to illustrate a regional
      approach along with in-depth, specific analyses. Fatality rates, which showed
      some decline in the 1980s, were fairly constant during the 1990s. Changes in
      nonfatal injury rates for this sector could not be assessed due to a lack of
      benchmark data. The main concerns identified in the 1989 NCASH report continue
      today: tractors are the leading cause of farm-related death due mostly to
      overturns; older farmers continue to be at the highest risk for farm fatalities;
      and traumatic injuries continue to be a major concern for youth living or working
      on U.S. farms. Fatal and nonfatal traumatic injuries associated with agricultural
      production are a major public health problem that needs to be addressed through
      comprehensive approaches that include further delineation of the problem,
      particularly in children and older adults, and identification of specific risk
      factors through analytic efforts. Continued development of relevant surveillance
      systems and implementation of appropriate interventions are the primary
      challenges for the current decade.

PMID- 12002375
TI  - Farm safety issues in Old Order Anabaptist communities: unique aspects and
      innovative intervention strategies.
AB  - The Amish and other Old Order Anabaptists have been inseparably linked with
      agriculture since coming to America. However few efforts have been identified
      which analyze the issues involved with Old Order Anabaptist farm injuries or
      present best practices for addressing these problems. As part of an effort to
      develop culturally appropriate and effective injury prevention strategies for use
      within the Old Order Anabaptist community, this article identifies important
      cultural issues that should be considered in understanding and attempting to
      reduce farm injures in this population, summarizes statistics concerning farm
      related fatalities among Old Order Anabaptists, and discusses methods which have
      been effectively used to address farm injuries within these communities. In the
      statistical analysis, 92 cases were identified that were classified as being work
      related or occurring in a farm work-related setting during the period 1980 to
      2000. Approximately 64% of the identified cases were children 15 years and under;
      and approximately 77% were male. Run-over incidents were the most frequent
      primary cause of the fatal injuries, while animal-related behavior was the most
      frequent secondary cause, reflecting agricultural practices that remain highly
      dependent upon the use of horses and mules. The authors believe evidence suggests
      that certain Old Order Anabaptist choices concerning farm safety issues may be
      directly related to their socio-religious beliefs, and that effective
      intervention strategies must also be sensitive to socio-religious beliefs.

PMID- 12002376
TI  - Factors influencing the occurrence and severity of farm accidents: comparing work
      related and nonwork-related events.
AB  - Economic incentives are emerging as useful preventive approaches to motivating
      farmers to adopt safer farming and managerial practices. The effectiveness of
      these programs and incentives will be enhanced by focusing resources on factors
      that play a critical role in contributing to farm accidents and the injury
      severity. A primary objective is to identify and assess the relative impact of
      factors that jointly influence the probability of work-related farm accidents
      relative to nonwork-related accidents and the severity of farm accidents. The
      model uses survey data on producer characteristics, farm organization, and work
      routines from the Georgia Healthy Farmers Project (GHFP). A probit model
      describing the factors that influence the probability of a work-related accident
      is estimated jointly with an ordered probit model for farm accident severity. The
      probit model indicates that older farmers and hired farm workers have higher
      probabilities of experiencing work-related accidents relative to nonwork-related
      events. Significant variables that influence the severity of farm accidents are
      more difficult to identify from the ordered probit models for both work-related
      and nonwork-related farm accidents.

PMID- 12002377
TI  - "Agriculture at risk: A report to the nation"--a historical review, critical
      analysis, and implications for future planning.
AB  - "Agricultural at Risk: A Report to the Nation" is a proceedings document of a
      three-year (1987-1990) policy development process entitled "Agricultural
      Occupational and Environmental Health: Policy Strategies for the Future." That
      process culminated in the emergence of occupational health and safety in
      agriculture as a public health policy issue in the U.S. Several agricultural
      health and safety programs evolved as direct or indirect consequences of this
      process, including, but not limited to, the NIOSH agricultural occupational
      health programs, The Kellogg Foundation agricultural health grants programs, and
      the prospective chronic health studies of pesticides (EPA-NlH funded). The
      Agriculture at Risk report resulted in 86 specific recommendations. The authors
      of this article reviewed each of these recommendations and rated them on a
      subjective scale as to their degree of attainment. They found that 44% of the
      recommendations had received moderate to substantial action. Most of the positive
      action was in the areas of research and coalition building. A noticeable lack of
      action was in the areas of standards and regulation, occupational health service
      delivery, and education categories. This article concludes with an analysis of
      the limitations of the AAR report, changes in exposed populations over the past
      decade, and specific recommendations on future actions to address the issues.

PMID- 12002378
TI  - Agricultural injuries in Central India: nature, magnitude, and economic impact.
AB  - A study was carried out in Madhya Pradesh (Central India) to collect data on
      injury-causing agricultural incidents during the period 1995-1999. The overall
      incidence rate was 1.25/1000 workers/year. About 9.2% of the incidents were
      fatal, and most of the fatal incidents were due to tractors and snakebites (42.9%
      each). About 77.6% of all incidents were due to farm machinery, 11.8% were due to
      hand tools, and the remaining 10.6% were due to other sources like snakes, wells,
      etc. Data on 1,911 incidents reported in 10 leading newspapers published during
      the five-year period (1995-1999) from different regions of the state were also
      collected and analyzed, which indicated that only major or roadside agricultural
      incidents were reported in newspapers. Based on the survey data, it was estimated
      that in the year 2000 there would have been about 17,480 agricultural incidents
      in Madhya Pradesh, causing death to about 2,050 workers and injuries to about
      16,770 workers, including amputations of limbs, burns, cuts, etc. Total monetary
      loss due to agricultural injuries in the state of Madhya Pradesh has been
      estimated as US $27 million/year.

PMID- 12002379
TI  - Histopathological approach to patterns of interstitial pneumonia in patient with
      connective tissue disorders.
AB  - It is well established that some patients with connective tissue disorders will
      suffer from pulmonary disease at some stage in their disease progression. This
      article concentrates on the interstitial pneumonias, seen in association with
      most types of connective tissue disorder, particularly in the ligh of non
      specific interstitial pneumonia (NSIP) being recognised as a distinct
      histological pattern. Most published articles on this subject precede recognition
      of NSIP and, as such, the relative incidence of patterns of interstitial
      pneumonia, as defined by the International Consensus Classification Committee for
      Interstitial Lung Disease (ICCILD), as well as the clinical and prognostic
      significance of these patterns is undergoing further scrutiny. In this review,
      the recognised histological patterns, namely usual interstitial pneumonia (UIP),
      non-specific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD),
      organising pneumonia (OP), reactive pulmonary lymphoid hyperplasia, desquamative
      interstitial pneumonia (DIP) and respiratory bronchiolitis-associated
      interstitial lung disease (RBILD) are reviewed systematically in relation to the
      various subgroups of connective tissue disorders. As yet, there are few published
      studies, but current evidence suggests that many cases previously classified as
      fibrosing alveolitis are likely to show a pattern of NSIP rather than UIP,
      particularly in relation to systemic sclerosis. The histological pattern of usual
      interstitial pneumonia, the most frequently seen pattern in biopsies from
      patients with idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis,
      appears to be comparatively rare. Furthermore, any biopsy showing a combination
      of histological patterns, a pattern of non-specific interstitial pneumonia or a
      pattern of lymphoid interstitial pneumonia/follicular bronchiolitis should be
      thoroughly investigated for a background connective tissue disorder, if
      previously unsuspected. Finally, the recently published prognostic data relating
      to these histological patterns in idiopathic disease should not be extrapolated
      to patients with connective tissue disorders.

PMID- 12002380
TI  - Donor-acquired sarcoidosis.
AB  - "Donor-acquired sarcoidosis" is defined as the development of sarcoidosis in
      presumably naive (non-sarcoidosis) transplant recipients who have received
      tissues or organs from donors who were not known or suspected to have active
      sarcoidosis. In reviewing the literature up until September of 1999, we found
      four publications describing a total of eight organs or tissues donated by
      subjects with sarcoidosis. These are the basis for this review. We draw upon
      these cases to discuss etiologic considerations for sarcoidosis, and suggest that
      donor-acquired sarcoidosis strengthens the view that sarcoidosis is caused by a
      transmissible agent, perhaps of infectious origin. Since not all recipients of
      organs from donors with active sarcoidosis develop sarcoidosis, host factors also
      appear to be important in disease pathogenesis. Less credence is ultimately given
      to external or environmental factors. Issues underlying host tolerance as a
      possible explanation for the reported absence of mortality or loss of allograft
      function during the limited periods of observation are also discussed.

PMID- 12002381
TI  - The neutralization of interleukin-5 as a therapeutic concept in allergic
      inflammation.
AB  - Interleukin-5 (IL-5) is an eosinophil differentiation factor. Therefore,
      increased levels of IL-5 in the bone marrow are associated with increased
      eosinophil numbers in blood. In addition, IL-5 increases the sensitivity of
      eosinophils towards other stimuli and delays their cell death. In contrast to
      other cytokines, IL-5 acts on a limited number of cells only. In fact, high
      affinity IL-5 receptors are exclusively expressed by eosinophils and basophils,
      but no other human cells. Therefore, neutralization of IL-5 appears to be an
      obvious approach to treat eosinophilic disorders, since no major side effects due
      to effects on other cells are expected. Results from animal experiments suggested
      that anti-IL-5 antibodies may have anti-asthmatic activities. In this article, I
      summarize our current knowledge regarding anti-IL-5 therapy and speculate on the
      potential use of these drugs in the future.

PMID- 12002383
TI  - Acute sarcoidosis subsequent to Wegener's granulomatosis: an unusual sequence of
      two granulomatous diseases.

PMID- 12002382
TI  - Pulmonary disease in patients with hematologic malignancies.
AB  - Patients with hematologic neoplasms frequently experience pulmonary disease. The
      possibility of a malignant involvement of the lung parenchyma is a well
      recognized and not unusual event, secondary spread due to lymphoproliferative
      disorders being the most common situation. Furthermore, the development and the
      advances in treatment options such as hematopoietic stem cell transplantation,
      radiation therapy and/or combined drug regimen use have significantly widened the
      spectrum of non-neoplastic pulmonary complications that can crop up in these
      patients. Infections, drug/radiation-induced toxicity, and graft-versus-host
      disease (GVHD)-related complications account by now for most pulmonary problems
      in hematologic patients and represent a difficult challenge both in diagnostic
      and in therapeutic terms for the clinician. The aim of this review is to
      highlight the clinicopathologic spectrum of lung diseases which can occur in the
      setting of hematologic malignancies. A particular emphasis is devoted to the
      diagnostic approach, high-resolution computed tomography (HRCT) assuming a key
      role since different patterns of CT abnormalities are associated with a different
      yield of the available diagnostic tools and may help in narrowing the
      differential diagnosis.

PMID- 12002384
TI  - Cytokine profile of broncho-alveolar lavage in BOOP and UIP.
AB  - BACKGROUND: The aim of our study was to compare clinical and BAL features of
      patients with bronchiolitis obliterans organizing pneumonia (BOOP) with those of
      patients with usual interstitial pneumonia (UIP) and control subjects. PATIENTS
      AND METHODS: This study reports on 14 patients with idiopathic BOOP. Diagnosis
      was made upon histology. Lung function tests were mostly normal. Chest X-ray and
      CT showed always a patchy consolidation, often associated with ground glass
      pattern. BAL was performed for cytology and for ELISA assessment of several
      cytokines (IL8, ILI0, IL12, gamma-interferon, IL 18, monocyte chemoattractant
      protein- 1). RESULTS: Cytology of BAL in BOOP showed a pattern of lymphocytic
      alveolitis (Lymphocytes: 0.36 x 10(6)/ml) associated with an increase in
      neutrophil and eosinophil counts (0.13 and 0.04 x 10(6)/ml respectively). Mean
      BALf levels in pg/ml of MCP-1, IL12 and IL18 were significantly increased in BOOP
      with respect to controls and UIP patients, while in UIP patients only a
      significant increase of IL8, MCP-1 and IL18 with respect to controls was
      detected. In addition, BALf levels of IL10, an anti-inflammatory cytokine, were
      significantly higher in BOOP patients with respect to controls and UIP patients.
      CONCLUSION: These findings are consistent with a marked degree of macrophage and
      lymphocyte activation in BOOP with an expansion of T helper-1 response. The
      concomitant increase of IL10 could be related to a limitation of the inflammatory
      process and the fibrotic evolution typical of this clinical picture.

PMID- 12002385
TI  - Gene expression profile analysis by DNA microarrays: a new approach to assess
      functional genomics in diseases.
AB  - A biologically based and potentially powerful way to characterize human diseases
      has arisen from the new science of genomics. One of the methodologies to provide
      a systematic way to observe and characterize gene expression programs is the DNA
      microarrays (also called gene chips). This modern genomic analysis tool shows the
      promise of providing an unbiased approach to detecting biologically relevant
      differences within clinically similar diseases. Taking advantage of the initial
      reports that appeared in the literature on this topic, the likely impact of a
      molecular taxonomic of interstitial lung disease subgroups based upon gene
      expression profiling is discussed.

PMID- 12002386
TI  - Bronchoalveolar glutathione and nitrite/nitrate in idiopathic pulmonary fibrosis
      and sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: Bronchoalveolar lavage (BAL) is useful in
      diagnosis and management of interstitial lung diseases. Glutathione (GSH)
      represents an important defence molecule against reactive oxygen species produced
      during inflammation, which underlies both idiopathic pulmonary fibrosis (IPF) and
      sarcoidosis. Nitric oxide has been suggested as a marker of airway inflammation.
      The aim of this study was to examine the content of GSH and NO stable
      metabolites, nitrite/nitrate, in the BAL of a group of patients with IPF and
      sarcoidosis. METHODS: BAL was performed in 13 patients with newly diagnosed IPF,
      13 patients with sarcoidosis and 4 controls. Total GSH and nitrite/nitrate were
      measured. BAL was repeated, in 5 patients with IPF, after 6 and 12 months and GSH
      was measured again. RESULTS: IPF patients had significantly lower levels of total
      GSH compared to sarcoidosis patients or controls (129 +/- 22 vs. 324 +/- 40 and
      383 +/- 23 mM; p < 0.001) in the epithelial lining fluid (ELF). In patients with
      IPF (n = 5), total GSH levels in the ELF increased after 6 and 12 months (T0 = 98
      +/- 19; T6 = 219 +/- 22; T12 = 301 +/- 34 microM; p < 0.05) following therapy
      with immunosuppressive drugs such as corticosteroids, methotrexate, cyclosporin
      A. Levels of nitrite/nitrate were found significantly elevated in IPF (n = 8) and
      sarcoidosis (n = 10) patients compared to controls (230 +/- 37 and 216 +/- 36 vs.
      86 +/- 11 microM; p < 0.05). CONCLUSION: These observations support the role of
      inflammation and antioxidant defences in interstitial lung diseases and may
      provide insights into the pathogenesis of oxidant-induced interstitial disease
      and their therapy.

PMID- 12002387
TI  - Expression of sarcoidosis related genes in lung lavage cells.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous multiorgan disease of unknown
      cause. Some facts point to a genetically determined predisposition, like
      associations with certain Major Histocompatibility Antigens Class I- and II-types
      (MHC). Mycobacterial DNA has been found in about 30% of sarcoidosis patients
      within the granulomas, which has been interpreted as a probable trigger
      mechanism. METHODS: Cells from bronchoalveolar lavage (BAL) of sarcoidosis
      patients were stimulated with dead Mycobacterium avium and gene expression was
      studied after six hours. Gene expression was profiled by hybridization to PCR
      filters (Human UniGene Set RZPD-1). To avoid the detection of effects related to
      secondary and tertiary inflammatory messages, we compared gene expression in
      sarcoidosis with that of tuberculosis and extrinsic allergic alveolitis. After
      normalization genes up- or downregulated for a factor of at least 1.8 were
      further analyzed. Genes differentially expressed in sarcoidosis as well as in
      tuberculosis or EAA, respectively, were subtracted. RESULTS AND CONCLUSIONS: Four
      different genes were exclusively upregulated in sarcoidosis: fatty acid binding
      protein 4 (FABP4), B-MYB, and two EST's. FABP4 has already been described in some
      autoimmune diseases, but its function in sarcoidosis is unknown. B-MYB is a
      potent growth factor for haematopoietic cells including lymphocytes. It might be
      one of the central genes upregulated in sarcoidosis and by that inducing clonal
      expansion of sarcoidosis-antigen primed T-helper-lymphocytes. Clonal selection of
      T-helper cells might be facilitated by c-Akt together with Tcl-1, both also
      upregulated in sarcoidosis. For the two ESTs neither function nor location is
      known.

PMID- 12002388
TI  - Pioneers of sarcoidosis: Christian Frederick Heerfordt (1871-1953).

PMID- 12002389
TI  - Splenectomy in sarcoidosis: indications, complications, and long-term follow-up.
AB  - BACKGROUND: Management of splenic enlargement due to sarcoidosis consists of
      primarily medical therapy with prednisone, methotrexate or antimalarial drugs.
      Splenectomy is the last resort because of the concern about complications of
      surgery. AIM: This study was conducted to explore indications for splenectomy in
      sarcoidosis and to assess if complications associated with splenic removal were
      unacceptable. METHODS/RESULTS: 13 sarcoidosis patients had their spleens removed
      for one or more of the following four reasons: (1) Massive splenomegaly; (2)
      Severe hypersplenism; (3) Need for excluding lymphoma or malignancy; and (4)
      Precaution against splenic rupture. All patients received strict prophylactic
      protocol and were followed over a period ranging from 1 to 30 years. CONCLUSION:
      In this long term follow-up study none of the thirteen patients developed serious
      infections or sepsis. No deaths occurred that might be related to splenectomy.

PMID- 12002390
TI  - Serum concentrations of ionized calcium reflect renal function in patients with
      sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: Decrease in renal function was investigated in
      relation to altered metabolism of calcium in patients with sarcoidosis. METHODS:
      Fifty consecutive patients with pulmonary sarcoidosis (23 men and 27 women, 47 +/
      15 years as mean +/- SD) were studied on a daily diet consisting of 500 mg of
      calcium and 1000 mg of phosphorus. Renal functions were evaluated with Z scores
      of creatinine clearance (Ccr). RESULTS: Decreased renal function (Ccr Z score < 
      1) was detected in 13 out of 50 sarcoidosis patients (26.0%). In seven patients
      (14.0%) Ccr Z scores were less than -2; relative risk (RR) and 95% confidence
      interval (95% CI) were 13.9 and 2.97 to 64.7, respectively. Ccr Z score
      correlated most significantly with serum concentration of ionized calcium (sCa2+)
      (r = -0.574, 95% CI, -0.735 to -0.352, p < 0.0001). A stepwise regression
      analysis adjusting for observation time, serum concentration of calcium and 1,25
      Dihydroxyvitamin D, urinary excretion of calcium, and urinary calcium crystals
      showed that sCa2+, together with angiotensin-converting enzyme activity in serum,
      was the most contributory variable to decrease in renal function in sarcoidosis
      patients (R2 = 0.391, p < 0.0001). A cutoff value of sCa2, 1.30 mmol/L obtained
      with a discriminant analysis showed 69.2% of sensitivity and 89.2% of specificity
      for decreased renal function. CONCLUSIONS: We reported increased prevalence of
      decreased renal function among sarcoidosis patients. sCa2+ was a significant
      index that reflected the alteration of renal function.

PMID- 12002391
TI  - Predictive value of ANCA in atypical primary brain localization of Wegener's
      granulomatosis.
AB  - Wegener's Granulomatosis is a necrotizing vasculitis generally involving upper
      and lower respiratory tract and kidneys. The central nervous system is involved
      in less than 10% of the patients during the course of the disease and primary
      involvement is even rarer. We present and discuss the case of a patient with
      primitive cerebral localization of Wegener's Granulomatosis in which the
      diagnosis and the beginning of correct therapy were delayed, in spite of a rising
      c-ANCA titer, due to a misinterpretation of a bioptic specimen. This delay caused
      renal damage and pulmonary cavitations which needed a long time to recover. This
      case report suggests that the central nervous system can be the site of a primary
      localization of Wegener's Granulomatosis even without any other organ
      involvement. The diagnosis must be made as soon as possible in order to prevent
      spread to other sites since the disease is usually very aggressive and severe.

PMID- 12002392
TI  - What did mummy say? Dyadic interactions between young "hard to manage" children
      and their mothers.
AB  - Thirty preschoolers rated as "hard to manage" on Goodman's (R. Goodman, 1997)
      Strengths and Difficulties Questionnaire (SDQ), and a group of matched control
      children were observed and recorded on audiotape at home, interacting with their
      mothers (Time 1). At the 18-month follow-up home visits (Time 2), the children
      and mothers were filmed across 4 observation settings. Mother-child interactions
      were rated on affect, control, responsiveness and "connectedness" of
      communication. At Time 1, mothers of the "hard to manage" group used more
      negative control and engaged in fewer connected conversations than did mothers in
      the control group. At Time 2, mothers of the "hard to manage" group displayed
      higher levels of negative control and lower levels of positive control. These
      results are discussed in terms of the importance of examining connected
      communication and different observation contexts when examining dyadic mother
      child interactions.

PMID- 12002393
TI  - Victimization in South Korean children's peer groups.
AB  - This study reports a cross-sectional investigation of the behavioral, academic,
      and psychosocial correlates of victimization in South Korean children's peer
      groups. The participants were 122 children (66 boys, 56 girls; from 10-12-years
      old) recruited from a primary school in Seoul, South Korea. Multi-informant
      assessments (peer nominations, teacher ratings, and self-reports) of peer
      victimization, social behavior, loneliness/social dissatisfaction, and academic
      functioning were obtained. Multivariate analyses indicated that peer
      victimization was associated with poor academic adjustment, loneliness,
      submissive-withdrawn behavior, aggression, and low levels of assertive-prosocial
      behavior. These findings suggest that there is considerable similarity in the
      social processes underlying peer group victimization across South Korean and
      Western cultural settings.

PMID- 12002394
TI  - A multisource exploration of the friendship patterns of children with and without
      learning disabilities.
AB  - Friendship patterns of 117 children with learning disabilities (LD) and 115
      children without LD in Grades 4-8 were examined. In comparison with children
      without LD, boys with LD had fewer mutual friends, children with LD had more
      friends with learning problems and more younger friends, and children with LD in
      Grades 4-6 had less stable relationships. With regard to friendship quality,
      children with LD reported higher levels of conflict, lower levels of validation,
      and more problems with relationship repair than did children without LD. The
      findings were discussed in terms of factors that have been found to enhance
      friendship such as proximity and similarity, and the social skills difficulties
      that have been associated with learning disabilities.

PMID- 12002395
TI  - Sibling collusion and problem behavior in early adolescence: toward a process
      model for family mutuality.
AB  - Sibling collusion is a process by which siblings form coalitions that promote
      deviance and undermine parenting. Collusive sibling processes were identified and
      measured using macro ratings of videotaped family interactions. Hypotheses were
      tested on a multiethnic sample of urban youth, with a target child identified as
      either "high risk" (n = 26) or "normative" (n = 26), and their families. Siblings
      in families with a high-risk target child showed reliably higher rates of
      collusion than those in families with a normative target child. Sibling collusion
      also accounted for variance in problem behavior after controlling for involvement
      with deviant peers. Findings suggest that deviant conduct forms a common ground
      among siblings, potentially amplifying risk of mutuality in problem behavior
      during early adolescence. These data also indicate that attention to sibling
      relationship processes is relevant to family interventions designed to mitigate
      the development of behavior problems.

PMID- 12002396
TI  - The relationship between self-complexity and depressive symptoms in third and
      seventh grade children: a short-term longitudinal study.
AB  - The goal of this study was to test the diathesis-stress component of Linville's
      and Morgan and Janoff-Bulman's models of the relationship between self-complexity
      and depressive symptoms in a sample of third and seventh grade children (P. W.
      Linville, 1985, 1987; H. J. Morgan & Janoff-Bulman, 1994). The procedure involved
      an initial assessment of self-complexity and depressive symptoms. The procedure
      also involved a follow-up assessment, 10 weeks later, in which depressive
      symptoms and the occurrence of negative events were assessed. Contrary to
      hypotheses, neither high levels of total nor positive self-complexity served as a
      buffer against the onset of depressive symptoms following the occurrence of
      negative events. In line with hypotheses, however, high levels of negative self
      complexity interacted with the occurrence of negative events to predict increases
      in depressive symptoms in seventh but not third grade children.

PMID- 12002397
TI  - The tripartite model and dimensions of anxiety and depression: an examination of
      structure in a large school sample.
AB  - This study was designed to build on recent findings that (a) factors of the
      tripartite model in adults are not uniformly related to all anxiety disorder
      dimensions as recent research has suggested (T. A. Brown, B. F. Chorpita, & D. H.
      Barlow, 1998; S. Mineka, D. W. Watson, & L. A. Clark, 1998), and (b) the
      tripartite model of emotion appears to have increasing support and utility in
      child samples (e.g., C. J. Lonigan, E. S. Hooe, C. F. David, & J. A. Kistner,
      1999). The structural relations were evaluated among tripartite factors and
      dimensions representing selected anxiety disorders and depression in a large
      multiethnic school sample of children and adolescents. General aspects of the
      tripartite model were supported. For example, Negative Affect was positively
      related with all anxiety and depression scales, and Positive Affect was
      negatively correlated with the depression scale. Consistent with previous
      observations in adult samples, Physiological Hyperarousal was positively related
      with Panic only, and was not significantly positively correlated with other
      anxiety syndromes. The structure of the best fitting model appeared robust across
      different grade levels and gender. In follow-up analyses. several interactions of
      grade level with structural parameters emerged, such that the relation of some of
      the tripartite factors with anxiety and depression were noted to increase or
      decrease across grade level.

PMID- 12002398
TI  - Factors affecting the adsorption of buchnericin LB, a bacteriocin produced by
      Lactobacillus [correction of Lactocobacillus] buchneri.
AB  - Buchnericin-LB adsorbs to gram-positive but not to gram-negative bacteria. The
      tested gram-positive bacteria were species of Lactobacillus, Pediococcus,
      Leuconostoc, Enterococcus, Lactococcus, Listeria, Bacillus, Staphylococcus; gram
      negative bacteria belonged to the genera Salmonella, Escherichia, Yersinia and
      Pseudomonas. Buchnericin-LB adsorption depended on pH but not on time and
      temperature. Also some anions of salts and lipoteichoic acid reduced or inhibited
      its adsorption. Treatment of cells and cell walls of sensitive bacteria with
      detergents, organic solvents or enzymes did not affect subsequent binding of
      buchnericin-LB. Treatment with buchnericin-LB caused sensitive cells to lose high
      amounts of intracellular K+ ions and UV-absorbing materials and became more
      permeable to o-nitrophenol-beta-D-galactopyranoside. Buchnericin-LB (640-2560
      AU/ml) decreased the colony forming units (99%) and absorbance values of Listeria
      monocytogenes and Bacillus cereus. These results indicate that the mode of action
      of buchnericin-LB is bactericidal and its lethal effect is very rapid.

PMID- 12002399
TI  - A new insertion sequence element, ISLdl1, in Lactobacillus delbrueckii subsp.
      lactis ATCC 15808.
AB  - A new insertion sequence element designated ISLdl1 has been isolated and
      characterized from Lactobacillus delbrueckii subsp. lactis ATCC 15808. It is the
      first IS element of L. delbrueckii subsp. lactis described. ISLdl1 is a 1508 bp
      element flanked by 26 bp imperfect inverted repeats, and generates an 8 bp AT
      rich target duplication upon insertion. It contains one ORF encoding a protein of
      455 amino acids. This protein shows significant homology to the transposases of
      the ISL3 family and to other bacterial transposases and putative transposases,
      and no homology to other proteins. Based on these structural features, ISLdl1
      belongs to the ISL3 family. ISLdl1 is present in about 10-12 copies in the genome
      of ATCC 15808 based on Southern hybridization analysis. Location sites of eight
      ISLdl1 copies have been determined in more detail by cloning and sequencing one
      or both of the flanking regions of each ISLdl1 copy. ISLdl1 or ISLdl1-like IS
      elements were found exclusively in Lactobacillus delbrueckii species and in all
      strains of subsp. lactis tested. The nucleotide sequence of ISLdl1 is deposited
      under the accession number AJ302652.

PMID- 12002400
TI  - Diversity in soil fungi from undisturbed and disturbed Celtis tala and Scutia
      buxifolia forests in the eastern Buenos Aires province (Argentina).
AB  - The rhizospheric soil microfungi from a native forest (undisturbed and disturbed)
      were studied using soil dilution plate and soil washing methods. Fungi were
      isolated using slightly acid and alkaline culture media. 54 taxa were isolated:
      49 from undisturbed forest soil and 37 from disturbed forest soil. Acremonium
      sp., Aspergillus ustus, Coemansia pectinata, Doratomyces stemonitis, Fusarium
      solani, F. oxysporum, Gliocladium roseum, Humicola fusco-atra, Mortierella sp.,
      Penicillium lilacinum, Trichoderma harzianum, and T koningii, showed the highest
      frequency, in both, undisturbed and disturbed forests. In undisturbed soil forest
      the biodiversity index was 3.97 whereas in disturbed ones was 3.89.

PMID- 12002401
TI  - Mycorrhizal growth in pure cultures in the presence of pesticides.
AB  - The effects of pesticides on 64 ectomycorrhizal fungi of boreal forest trees were
      studied in vitro. The pesticides (fungicides: benomyl, chlorothalonil, copper
      oxychloride, maneb and propiconazole; herbicides: chlorthiamid, glyphosate,
      hexazinone, linuron and terbuthylazine; insecticide: cypermethrin) were selected
      as those commonly used in Nordic forest nurseries and afforestation sites. In
      general, the fungicides proved to be more toxic to ectomycorrhizal fungi than the
      herbicides and cypermethrin. The fungicides, chlorothalonil and propiconazole,
      had the clearest inhibitory effect on growth of mycorrhizal fungi. Conversely,
      maneb, glyphosate and terbuthylazine stimulated the growth of some mycorrhizal
      fungi. Leccinum versipelle and L. scabrum, Paxillus involutus and Cenococcum
      geophilum were the most sensitive ectomycorrhizal fungi to the various
      pesticides.

PMID- 12002402
TI  - Horizontal and vertical movement of Pseudomonas fluorescens toward exudate of
      Macrophomina phaseolina in soil: influence of motility and soil properties.
AB  - The role of motility and cell surface hydrophobicity in transport and dispersal
      of Pseudomonas fluorescens strains LAM1-hydrophilic, LAM2-hydrophobic and LAM(NM)
      (non-motile mutant of LAM2) under different soil conditions was studied. Maximum
      adhesion was recorded for LAM2 in clay loam (70%), followed by sandy loam (68%)
      and sandy soil (40%). Vertical migration of P fluorescens isolates in soils was
      recorded at 5 and 25 cm flow of wafer or M. phaseolina exudate. In all the
      treatments, LAM1 exhibited maximum migration followed, by LAM2 and LAM(NM). The
      rate of migration of such isolates was lowered in water irrigated soils compared
      to those irrigated with M. phaseolina exudate. In sandy soil, cells of LAM1
      migrated up to 13 cm in comparison to LAM2 (11 cm) and LAN(NM) (9 cm) at 5 cm
      flow of fungal exudate. Population of LAM1, LAM2 and LAM(NM) was 5.7, 5.68 and
      5.61 log cfu g(-1) soil at 1 cm depth, but it decreased to 2.56, 2.21 and 1.99
      log cfu during migration up to 11 cm in sandy soil at 5 cm flow of fungal
      exudate. Greater motility was observed in sandy soil irrigated with water or
      fungal exudate, followed by sandy loam and clay loam. In general, filtration
      coefficient (lambda) of P. fluorescens was higher in soils irrigated with 5 cm of
      water or exudate than with 25 cm of irrigation. The horizontal movement of P.
      fluorescens strains in sandy soil adjusted at different psi m showed marked
      reduction with decrease in psi m. The non-motile LAN(NM) did not show chemotactic
      response and migrated up to a maximum of 3 mm in saturated soils (0 kPa). After
      96 h, LAM1 and LAM2 migrated upto 35 and 29 mm respectively in sandy soil. Motile
      isolates had significantly greater colonization of M. phaseolina sclerotia over
      the non-motile mutant.

PMID- 12002403
TI  - Clostridium thermobutyricum: growth studies and stimulation of butyrate formation
      by acetate supplementation.
AB  - Clostridium thermobutyricum produces butyrate as the main fermentation product
      from glucose, and from yeast extract, which is required for substantial growth.
      After sequential transfer in the presence of increasing butyrate concentrations,
      strain JW 171 K grew in the presence of up to 350 mM butyrate either at pH 5.5 or
      at pH 8.0 and at 40 degrees C as well as at 60 degrees C. This result indicated
      that butyrate-dependent growth inhibition was independent from the concentration
      of undissociated butyric acid. Increased butyrate concentration decreased the
      level of tolerated glucose from above 15% to below 10%. At 0.05 and 2.0% (wt/vol)
      yeast extract, the Y(Glucose) was 30 and 55 g dry weight cells per mole glucose,
      respectively. Y(ATP) values between 18 and 21 g weight cells per mole ATP,
      obtained after growth in the presence of 2% yeast extract, indicate that the
      butyrate fermentation under thermophilic growth conditions is as energy efficient
      as it is under mesophilic conditions. Externally added acetate stimulated the
      production of butyrate. Supplemented 14C-acetate was converted to butyrate,
      resulting in the formation of 44% labeled butyrate (i.e. formed from 14C-acetate)
      and 56% unlabeled butyrate (formed from glucose and yeast extract). Continuous
      removal of H2 in batch cultures led to a shift in the fermentation products from
      more butyrate to the more oxidized and more energy yielding acetate.

PMID- 12002404
TI  - Polymerase chain reaction as a sensitive and rapid method for specific detection
      of Mycoplasma pneumoniae in clinical samples.
AB  - The fast diagnosis of Mycoplasma primary atypical pneumonia is impaired by the
      lack of routinely available culture methods for isolation of Mycoplasma
      pneumoniae from clinical specimens. Likewise, serological methods commonly used
      for diagnosis are insensitive and non-specific. In this study, we have
      established and applied the polymerase chain reaction (PCR) technique to detect
      M. pneumoniae DNA in clinical samples originating from the respiratory tract. The
      PCR results were compared with those from culture and serology tests. To
      standardize the detection of M. pneumoniae by PCR, we first used DNA from culture
      grown organisms and clinical samples seeded with M. pneumoniae. PCR amplification
      was performed with M. pneumoniae-specific primers to amplify 144, 153 and 631 bp
      DNA fragments by using primer pairs MP5-1/MP5-2, P1-178/P1-331 and P1-178/P1-809,
      respectively. The amplification of the 631 bp DNA fragment was found to be most
      sensitive for the detection of M. pneumoniae. Using the most sensitive PCR, a
      total of 47 respiratory specimens from patients suspected of community acquired
      pneumonia were tested. While none of the specimens were positive for M.
      pneumoniae in culture, 6 specimens gave positive results by PCR. In 4 out of the
      5 PCR positive samples tested serologically, the results were supported by
      elevated levels of anti-mycoplasma IgG/IgM/IgA. Thus, these results suggest that
      PCR is the most sensitive method to detect M. pneumoniae in clinical specimens.

PMID- 12002405
TI  - Isolation and characterization of mutants of two diazotrophic cyanobacteria
      tolerant to high concentrations of inorganic carbon.
AB  - Diazotrophic heterocystous cyanobacteria Nostoc calcicola and Anabaena sp. ARM
      629 were investigated for their ability to grow in presence of sodium bicarbonate
      (NaHCO3) or carbon dioxide (CO2) under cultural conditions. Maximum growth was
      observed in 75 mM NaHCO3 and 5% CO2 in N. calcicola and Anabaena ARM 629,
      respectively. Although their growth rate declined, N. calcicola and Anabaena sp.
      could tolerate upto 250 mM NaHCO3 and 20% CO2, respectively. N-methyl-N'-nitro N
      nitrosoguanidine induced mutants of these cyanobacteria were isolated which
      showed growth upto 1 M NaHCO3 (N. calcicola) or 50% CO2 (Anabaena sp.) in
      comparison to their wild types. The mutants also showed cross-resistance to
      either of the inorganic carbon compounds, which was not observed for wild type.
      It was concluded that mutants were altered in multiple properties enabling them
      to grow at elevated levels of inorganic carbon compounds.

PMID- 12002406
TI  - Evidence for genotypic differences between the two siderovars of Pseudomonas
      tolaasii, cause of brown blotch disease of the cultivated mushroom Agaricus
      bisporus.
AB  - Sixteen representative isolates of Pseudomonas tolaasii, the causal agent of
      brown blotch of the cultivated mushroom Agaricus bisporus, were previously
      assigned to two siderovars (sv1 and sv2) on the basis of pyoverdines synthesized.
      Each isolate was pathogenic and produced a typical white line precipitate when
      cultured adjacent to Pseudomonas "reactans" strain LMG 5329. These 16 isolates of
      P. tolaasii, representing sv1 and sv2, were further characterized using genotypic
      methods to examine the relationships between the isolates. Rep-PCR studies
      revealed two distinct patterns from these isolates, which were consistent with
      the siderovar grouping. Ribotyping differentiated P. tolaasii LMG 2342T (sv1) and
      PS 3a (sv2) into two distinct ribotypes. A pair of primers, targeted to a 2.1-kb
      fragment of tl1 (encoding a tolaasin peptide synthetase), yielded the same PCR
      product from P. tolaasii LMG 2342T (sv1) and PS 22.2 (sv1), but not from PS 3a
      (sv2). Southern blot analysis indicated that homologues of tl1 are present in PS
      3a, but the pattern of hybridization differed from PS 22.2 and LMG 2342T.
      Sequence determination and analysis of the internally transcribed spacer region
      ITSI for P. tolaasii LMG 2342T, LMG 6641, and PS 3a strains further supported the
      presence of the two siderovars. It is concluded that considerable genotypic
      differences exist among Finnish isolates of P. tolaasii causing brown blotch
      disease on the cultivated mushroom, which is in agreement with the phenotypic
      diversity highlighted through previous siderotyping studies.

PMID- 12002407
TI  - Growth hormone replacement does not elevate albuminuria in GH-deficient adults.
AB  - Minor elevations in urinary albumin excretion rate (Ualb.V) are likely to be
      associated with renal function loss and increased cardiovascular risk. Since
      urinary albumin excretion is affected by the growth hormone (GH)-insulin-like
      growth factor-1 (IGF-1) axis, we evaluated the effect of 6 months GH replacement
      (1U/day, n=8 and 2U/day, n=16) on urinary protein handling in 24 non-diabetic,
      normotensive GH-deficient adults (12 men and 12 women), of whom 8 patients
      received placebo during 6 months, followed by active GH treatment. Plasma IGF-1
      increased from 11.4 (8.1-15.8) nmol/L (median, interquartile range) to 35.4 (22.3
      44.1) nmol/L (p<0.001 versus change after placebo; median Z-score reached +0.2)
      after 6 months GH. and remained unaltered after placebo. Overnight Ualb.V was 4.0
      (3.1-4.9) microg/min before and 4.6 (2.4-8.2) microg/min after GH (p>0.10).
      Likewise, urinary IgG excretion rate did not significantly change after GH (0.71
      (0.52-1.20) microg/min before GH versus 0.80 (0.51-1.56) microg/min after GH;
      p>0.10). No significant changes were observed in creatinine clearance (p>0.10)
      and mean arterial pressure (p>0.10). No changes in any of these parameters were
      observed after placebo. Individual changes in Ualb.V were positively correlated
      with changes in plasma IGF-1 (r(s)=0.41, p=0.05) and with changes in mean
      arterial pressure (r(s)=0.49, p<0.02). The present study shows that 6 months GH
      replacement, increasing plasma IGF-1 within the physiological range, does not
      result in a clinically relevant increase in urinary protein excretion in GH
      deficient adults. The correlation between changes in plasma IGF-1 and in
      albuminuria supports the rationale to avoid supraphysiological IGF-1 levels.

PMID- 12002408
TI  - Elevated serum methylmalonic acid. How much comes from cobalamin deficiency and
      how much comes from the kidneys?
AB  - Serum methylmalonic acid (S-MMA) as a sensitive indicator of cobalamin deficiency
      was introduced more than 10 years ago. The use of this method for identifying
      patients with cobalamin deficiency reflects much higher prevalence figures than
      was previously thought. In this review, all major studies on the subject are
      analysed. The least common denominator that could explain the probably overrated
      prevalence figures is the deteriorated renal function accepted for inclusion in
      virtually all the studies. A strong association between S-MMA and S-creatinine,
      even within the normal range for creatinine. has become increasingly apparent. At
      present, it is impossible to estimate how much of elevated S-MMA comes from
      impaired renal function and how much comes from impaired cobalamin metabolism.
      Thus, the use of S-MMA as the sole indicator of cobalamin deficiency cannot be
      recommended.

PMID- 12002409
TI  - Part of purified human plasma kallikrein removed together with a remaining IgG
      fraction--immunoblot experiments and functional tests.
AB  - In the present study it is shown that a preparation of highly purified plasma
      kallikrein (specific activity 81 S-2302 U/mg) still contained small amounts of an
      IgG fraction. Amidase assays of the fresh enzyme with four peptide substrates (S
      2302, Bz-Pro-Phe-Arg-pNA, S-2366, S-2222) did not reveal any inhomogeneity, and
      immunoblot experiments with antibodies against prekallikrein yielded only an 85
      kD double band. After a storage period (2 years at -70 degrees C), S-2366 and S
      2222 amidase activities not reflecting the initial kallikrein appeared.
      Immunoblot studies with Fc-specific antibodies against IgG showed a 170 kD band,
      and immunoblots with a monoclonal antibody against prekallikrein demonstrated
      that, in addition to the 85 kD band, a band with a mol weight of about 152 kD
      could also be detected. Immunoblots showed that only 85 kD kallikrein was
      recovered in the eluate from Protein G columns, and amidase assays based on S
      2302 and Bz-Pro-Phe-Arg-pNA showed a recovery of about 70%. The other part of the
      kallikrein (30%) was removed along with the additional S-2366 and S-2222
      activities and the IgG3 fraction present. The theory is advanced that the
      additional activity reflects a kallikrein fraction with a mol weight of about 152
      kD, and is present in the fresh enzyme preparation in inactive complex with IgG.
      Storage of the kallikrein preparation led to some weakening of this complex and
      the appearance of functional activities of the kallikrein fraction involved.

PMID- 12002410
TI  - Ambulatory morning growth hormone concentrations increase in men and decrease in
      women with age.
AB  - A remarkable 80-fold difference in median growth hormone (GH) values in young
      adult men and women was recently found in a study of sera taken in ambulatory
      state in the morning, after overnight fasting. In this study, the effect of
      ageing on morning ambulatory GH levels was investigated in 254 apparently healthy
      men, 21-75 years of age, and 40 women, 21-85 years. Furthermore, the effect of
      oestradiol on morning GH values was studied in 19 postmenopausal women, 51-79
      years, treated with subcutaneous implants of 17beta-oestradiol (E2). The sera
      were analysed for GH, sex hormone-binding globulin (SHBG), E2, and in the men,
      also for testosterone (T). The morning GH levels increased (p<0.0001) with age in
      a group of 195 men of 41-75 years. After adjustment for age, an inverse
      correlation (p <0.05) was found between the levels of GH and free androgen index
      (T/SHBG) and a direct correlation between GH and SHBG. These relationships were
      more pronounced before the age of 60 than after. In the women, the GH levels
      decreased (p<0.01) with age and the gender difference of median values was
      reduced from 102-fold at younger age, 21-39 years, to 12-fold in elderly
      individuals, 60-75 years. In the E2-treated postmenopausal women, the morning GH
      values were similar to those of an untreated control group, indicating that the
      decrease with age in the morning GH levels in women is not a result of lower
      oestrogen levels alone. The gender difference in median ambulatory morning GH
      values decreased from 102-fold at a mean age of 25 years to 12-fold at a mean age
      of 68 years owing to opposite changes with age in men and women: an increase in
      men and a decrease in women.

PMID- 12002411
TI  - Single determination of plasma ACTH using an immunoradiometric assay with high
      detectability differentiates between ACTH-dependent and -independent Cushing's
      syndrome.
AB  - The purpose of this retrospective study was to elucidate the value of an ACTH
      assay with high detectability to differentiate between ACTH-dependent and 
      independent Cushing's syndrome. The study was based on the case records of 56
      patients with Cushing's syndrome comprising 34 patients with ACTH-dependent
      Cushing's syndrome and 22 patients with ACTH-independent Cushing's syndrome.
      Basal morning plasma 1-39 ACTH was measured using an immunoradiometric assay
      (IRMA) with a normal range of 1.8-11 pmol/L. Peripheral corticotrophin-releasing
      hormone (CRH) tests were performed in 24 and 17 patients with ACTH-dependent and 
      independent Cushing's syndrome, respectively. Using a single ACTH measurement, a
      complete separation was observed between the two defined groups, with a cut-off
      value of 2.4 pmol/L. Mean ACTH concentration was 14.4 pmol L (range 2.5-47.7
      pmol/L) in ACTH-dependent Cushing's syndrome and 0.6 pmol/L (range 0.2-2.2
      pmol/L) in ACTH-independent Cushing's syndrome. The range of separation between
      the two groups was further increased by using two ACTH measurements in each
      patient or peripheral stimulation with CRH. It is concluded that in the majority
      of patients with Cushing's syndrome a single basal morning ACTH determination is
      sufficient to discriminate between ACTH-dependent and ACTH-independent Cushing's
      syndrome. In borderline cases with ACTH in the range 2-3 pmol/L, repeated
      measurements might be necessary. The peripheral CRH test was not superior to
      repeated ACTH measurements.

PMID- 12002412
TI  - Effects of octreotide on serum insulin-like growth factor I and insulin-like
      growth factor binding proteins in patients with cirrhosis.
AB  - Hyperinsulinaemia and reduced insulin sensitivity are common features in patients
      with cirrhosis. Octreotide, a long-acting somatostatin analogue, is used in
      cirrhotic patients in the treatment of bleeding oesophageal varices. Octreotide
      has potent effects on the growth hormone (GH)/insulin-like growth factor I (IGF
      I) axis in healthy subjects. but the effects on the GH/IGF-I axis in patients
      with cirrhosis have been described only briefly. The effects of a 12 h infusion
      of octreotide (bolus 0.75 microg/kg followed by 0.75 microg/kg/h) in 25 subjects
      (normals n=9, compensated cirrhotics n=8, decompensated cirrhotics n=8) were
      compared with those in placebo-treated controls (n=19) during fasting conditions.
      IGF-I, free IGF-I, IGF binding proteins (IGFBPs), insulin, C-peptide, GH and
      glucose were measured. Insulin resistance was calculated using the HOMA method.
      Octreotide reduced levels of total IGF-I in patients with compensated cirrhosis
      (p=0.03) and free IGF-I in decompensated cirrhosis (p<0.01). Insulin resistance
      was significantly reduced in normal subjects. whereas the reduction in insulin
      resistance did not reach statistical significance in patients with cirrhosis. In
      normal subjects, octreotide increased the IGFBP-1 area under curve threefold
      (p<0.01) and decreased IGFBP-3 levels (p<0.01), but these effects were blunted in
      the cirrhotic patients. Similarly, the reduction of insulin and C-peptide was
      blunted in the cirrhotic patients, whereas a significant reduction in GH was
      demonstrated in all groups. The effects of octreotide on the GH/IGF-I axis are
      mitigated in patients with cirrhosis and this may be a reflection of relative
      hyperinsulinaemia during octreotide treatment in these patients.

PMID- 12002413
TI  - Cytokeratin-positive cells in preoperative peripheral blood and bone marrow
      aspirates of patients with colorectal cancer.
AB  - Detection of cytokeratin-positive cells in bone marrow and peripheral blood may
      have prognostic significance in cancer patients. Furthermore, a correlation
      between uPAR expression on micrometastases and patient prognosis has been
      suggested. However, in patients with colorectal cancer, preoperative detection
      and characterization of tumour cells in bone marrow and peripheral blood, using
      an immunocytochemical approach, have not yet been substantiated as a prognostic
      tool. METHODS: Forty-one bone marrow aspirates and 38 peripheral blood aspirates,
      obtained preoperatively from patients with colorectal cancer, were
      immunocytochemically screened for cytokeratin-positive cells. Where cytokeratin
      positive cells were observed, an additional microslide was double immunostained
      for simultaneous detection of cytokeratin and uPAR/CD87. RESULTS: Cytokeratin
      positive cells were observed in 4 out of 41 bone marrow aspirates (10%). None of
      the isolated cytokeratin-positive cells expressed uPAR. In peripheral blood, no
      cytokeratin-positive cells were observed. CONCLUSION: The present study does not
      support the introduction of a routine immunocytochemical identification of
      cytokeratin-positive cells in preoperatively obtained bone marrow aspirates or
      peripheral blood from patients with colorectal cancer.

PMID- 12002414
TI  - Increased levels of markers of vascular inflammation in patients with coronary
      heart disease.
AB  - Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory
      cytokines and C-reactive protein (CRP) have been associated with atherosclerotic
      disease states. The aim of the present study was to evaluate whether circulating
      levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion
      molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients
      with coronary heart disease (CHD) compared with healthy controls, and to study
      possible associations between these sCAMs, tumour necrosis factor alpha
      (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study
      included 193 patients in various stages of CHD and 193 matched controls. To
      evaluate any possible influence of acute phase reaction, reinvestigation was
      performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1,
      sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD
      patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by
      age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E
      selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender
      (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while
      IL-6 predicted CRP but none of the sCAMs measured. This might indicate that
      TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in
      vivo.

PMID- 12002415
TI  - Measured muscle sodium content in biopsy specimens is a reflection of true
      intracellular content.
AB  - Determined on the basis of small skeletal muscle biopsies, muscle sodium content
      has a very high coefficient of variation. Furthermore, at least some of the
      measured sodium must originate from the extracellular space. In order to assess
      the applicability of the measurement of intracellular sodium on small muscle
      biopsy specimens, the measured sodium content was related to the content of dry
      solids in 25 muscle biopsy samples, and compared with the theoretical content of
      sodium with varying extra- and intracellular water content in biopsy samples.
      Four of the 25 measurements were clearly outliers. Disregarding these outliers,
      it was found that muscle sodium content varied with intracellular water content,
      whereas the theoretical effect of addition of extracellular water could not
      account for the observed values. The difference depended upon the specified
      conditions, but the slope of the theoretical regression line (-25.92 mmol x (kg
      dry weight)(-1) x %(-1), which was closest to the observed slope, -8.55 mmol x
      (kg dry weight)(-1) x %(-1), differed substantially (p < 0.0001). No association
      was found between the primarily intracellular ions muscle potassium and muscle
      magnesium on the one hand and either muscle sodium or muscle water content on the
      other. The measured sodium content in muscle biopsy specimens, which are freeze
      dried and dissected, seems to reflect the true intracellular sodium content to
      some extent. The total content of sodium seems to be closely related to the
      content of water within the skeletal muscle cells.

PMID- 12002416
TI  - Biochemical parameters of endothelial dysfunction in cardiological syndrome X.
AB  - The endothelial dysfunction in cardiological syndrome X has been studied mainly
      by invasive methods and by measuring vasoactive mediator (nitric oxide (NO),
      endothelin-1) levels. Other parameters evaluating this dysfunction (defined as an
      imbalance between vascular relaxing and contracting factors, between procoagulant
      and anticoagulant or growth-inhibiting and growth-promoting substances) have not
      been used. METHODS: Twenty-five non-diabetic patients (16 men, 9 women) with
      cardiological syndrome X and 10 healthy volunteers (5 men, 5 women) were
      examined. Biochemical parameters: ET-1, the end products of nitric oxide
      metabolism (NOx), VEGF, vWF, betaTG, tPA, PAI-1 were measured before and during
      an ECG exercise tolerance test. The blood concentrations of testosterone and
      estradiol in men and LH, FSH and estradiol in women were tested. RESULTS: A
      significantly lower basal concentration of NOx (p=0.01), lower basal NOx/ET-1
      ratio (p<0.05) and higher levels of VEGF (p<0.05) were observed in patients with
      cardiological syndrome X. The male patients also had higher concentrations of
      estradiol (p<0.05). A significant decrease in tPA concentration and increase in
      betaTG was noticed during exercise, but with no differences between the study
      groups. CONCLUSIONS: Endothelial dysfunction in cardiological syndrome X
      manifests mainly in the regulation of vessel wall tonus. which was revealed by
      the decrease of NOx level and NOx/ET-1 ratio. VEGF elevation in syndrome X may
      result from chronic tissue ischaemia due to endothelial dysfunction. Exercise
      augments the prothrombotic activity of the blood, since a significant elevation
      in betaTG and decrease in tPA were observed after exercise.

PMID- 12002417
TI  - Circadian variations do not have a major impact on serum levels of soluble (S) L
      selectin (CD63L), S-intercellular adhesion molecule 1 (sICAM-1/CD54) and
      thrombopoietin in healthy individuals.
AB  - The systemic levels of many soluble adhesion molecules and cytokines are altered
      in hematologic malignancies, autoimmune diseases and serious infections. Among
      mediators that show altered serum levels are soluble (S) L-selectin (CD63L) and
      soluble intercellular adhesion molecule-1 (ICAM-1/CD54) expressed by
      immunocompetent and hematopoietic cells and the hematopoietic growth factor
      thrombopoietin (Tpo). In the present study, we investigated whether the serum
      levels of these mediators show circadian variations in healthy individuals.
      Venous blood serum levels of all three mediators showed only minimal variations
      when measured regularly during a 24-h period. In contrast, previous studies have
      demonstrated that the systemic levels of these mediators are markedly altered
      during serious bacterial infection (SL-selectin, sICAM-1) and severe
      thrombocytopenia (Tpo). The results suggest that serum sampling at standardized
      times is probably not required in the future clinical evaluation of these three
      parameters.

PMID- 12002418
TI  - Evidence of oxidative stress in the renal cortex of diabetic rats: favourable
      effect of vitamin E.
AB  - The aim of this study was to determine whether there are any disturbances of
      red/ox balance in the renal cortex of rats during the course of experimental
      diabetes. In the renal cortex of rats with streptozotocin-induced diabetes, the
      activity of superoxide dismutase (SOD) isoenzymes, glutathione peroxidase (GSH
      Pox). glutathione S-transferase (GST) and glutathione reductase (GSH-RED) was
      measured in the 5th, 10th and 15th weeks of diabetes. Free radical cell damage
      was assessed on the basis of malonyldialdehyde (MDA) concentration. The influence
      of lipophilic antioxidant vitamin E on these analytes was also studied. An
      increase in MDA concentration in the 10th and 15th weeks of diabetes correlated
      significantly with plasma glucose concentration (r=0.47; p<0.001). Moreover, MDA
      concentration was influenced by time (+); p<0.001, diabetes (+); p<0.001, vitamin
      E (-) p<0.001 (ANOVA). Plasma creatinine concentration in rats was elevated by
      diabetes (p<0.001), whereas vitamin E decreased the concentration (p<0.05).
      Vitamin E lowered the activity of GSHPox (p<0.001) and GST (p<0.01) (ANOVA). Our
      results indicate that during experimental diabetes, disturbances of red/ox
      balance lead to disturbance in renal function manifested as increased creatinine
      blood concentration. We suggest that oral supplementation of vitamin E protects
      the renal cortex of rats during experimental diabetes.

PMID- 12002419
TI  - Cytokines gene expression patterns of bovine milk during middle and late stages
      of lactation.
AB  - The cytokine mRNA profiles of the bovine mammary gland were investigated using
      newly developed TaqMan real-time polymerase chain reaction systems (Applied
      Biosystems, Foster City, CA, USA). Transcriptional activity of six cytokines,
      interleukin (IL)-2, IL-6, IL-12, interferon (IFN)-gamma, tumour necrosis factor
      (TNF)-alpha and granulocyte-macrophage colony stimulating factor (GM-CSF) was
      studied during the mid- and late-lactation stages. Transcripts for TNF-alpha, GM
      CSF, and IFN-gamma were detected in all samples of both stages. However, IL-12
      was only detected in 80 and 58 % of late- and mid-lactation samples,
      respectively. IL-12 expression was up-regulated in late lactation in comparison
      with the corresponding level in mid-lactation. The cytokines interaction in late
      lactation was more co-ordinated and their transcriptional levels were
      significantly correlated among each other, whereas, in mid-lactation significant
      correlation of the cytokines transcription was only seen with the TNF-alpha, GM
      CSF, and IFN-gamma. Cytokine mRNA profiles between mid- and late lactation showed
      significant differences, which can be attributed to the dramatic changes that the
      mammary gland is subjected to during late lactation. The significant elevation of
      IL-12 transcriptional activity in late lactation and its relevance to the mammary
      gland immunity is discussed.

PMID- 12002420
TI  - Hepatitis associated with herpes viral infection in the tortoise (Testudo
      horsfieldii).
AB  - Herpesvirus infection in tortoises is largely characterized by the development of
      respiratory clinical signs. Usually lesions develop in the respiratory, oral
      pharyngeal, intestinal tract and are accompanied by cutaneous and ocular lesions.
      In chelonids affected by herpesvirus, systemic-type lesions in organs such as the
      liver and spleen are commonly observed. In this paper we describe a case of
      multifocal necrotic hepatitis associated with herpesviruses in an adult female
      land tortoise of the species Testudo horsfieldii. This article is the first
      description of a viral hepatitis in Testudo spp. with lesions compatible with
      herpesvirus infection, with no clinical signs or lesions in the respiratory
      system, oral cavity or other organs.

PMID- 12002421
TI  - Investigation of haematological and biochemical side effects of tilmicosin in
      healthy New Zealand rabbits.
AB  - In this study, the effects of tilmicosin on some haematological and biochemical
      variables were investigated. Ten male New Zealand rabbits were used as material.
      The tilmicosin was injected (25 mg/kg body weight, subcutaneously as a single
      injection), and the rabbits were monitored for 4 days. No negative effects of
      tilmicosin on haematological and biochemical variables were observed, but it did
      cause a temporary decrease in red and white blood cell counts.

PMID- 12002422
TI  - Characterization and purification of cytosolic and membrane-bound protease(s) in
      adults of Haemonchus contortus.
AB  - The activity of protease(s) was observed separately in cytosolic and membrane
      bound protease(s) from male and female Hae monchus contortus (Nematoda:
      Trichostrongylidae). Different fractions showed optimum protease activity at 37
      degrees C, pH 8.5 and 8.0 mg casein concentration. The female fractions had a
      particularly high activity of protease(s) in comparison with the male fractions,
      especially of membrane-bound enzymes in the anterior half. Inhibition, activation
      studies revealed the presence of four kinds of protease(s) in cytosolic and
      membrane-bound fractions. Protease(s) in different fractions are purified to a
      greater extent by higher concentrations of saturated ammonium sulphate solution,
      i.e. ranging from 50 to 65%. The purification study revealed the presence of
      multiple forms of protease(s) in cytosolic and membrane-bound extracts of H.
      contortus.

PMID- 12002423
TI  - Nested reverse transcriptase-polymerase chain reaction for the detection of group
      A rotaviruses.
AB  - Rotaviruses are important pathogens associated with diarrhoeal diseases in almost
      all species of mammals. In the present study, a nested reverse transcriptase
      polymerase chain reaction (RT-PCR) for the detection of group A rotaviruses was
      developed, which is based on a target region in gene segment 6. Rotavirus strains
      of human, bovine, porcine, canine, feline, equine, and ovine origin were
      examined. Furthermore several faecal specimens, in which rotavirus had already
      been detected using other methods than PCR, were included in the study. A nested
      RT-PCR product was formed with all strains and faecal samples tested. The
      detection limit for virus-containing cell culture supernatant was 3 x 10(-2) [50%
      tissue culture infective dose (TCID50)] by RT-PCR and 3 x 10(-3) TCID50) by
      nested amplification. In order to examine the influence of the sample matrix on
      sensitivity, a rotavirus-negative faecal specimen was spiked with virus
      containing cell culture suspension of the porcine rotavirus OSU. The detection
      limit of the present PCR procedure was approximately 1.6 x 10(2) TCID50 per g
      faeces and could be increased by one order of magnitude using nested PCR. The
      present method for detection and identification of group A rotaviruses represents
      a powerful diagnostic tool and was shown to be applicable to rotaviruses of
      different origin, including human sources.

PMID- 12002424
TI  - Molecular identification of the Marek's disease virus vaccine strain CVI988 in
      vaccinated chickens.
AB  - The study describes three polymerase chain reaction (PCR) systems for the CVI988
      vaccine virus: the meq gene, the MDV BamHI-D/H 132 bp tandem repeat fragment and
      the MDV-gB gene. Whereas the PCR product of virulent MDV strains and of the
      CVI988 virus strain with the meq and the 132 bp primer sets differed for the two
      templates, the MDV-gB PCR products were similar. The sensitivity of the three
      PCRs was determined for the two templates: the CVI988 DNA was detected up to 2.48
      plaque forming units, and a MDV-1 DNA, was amplified with the 132 bp primers up
      to the 10(-3) DNA dilution, and up to the 10(-2) with the MDV-gB and meq gene
      primers. As conventional detection for the CVI988 vaccine virus is by tissue
      culture, the aim was to analyse the feasibility of the molecular detection of the
      vaccine virus in the vaccinated chick. In two experimental trials employing
      specific pathogen free and commercial Lohmann chicks, respectively, the vaccine
      virus replicated to a limited extent; it was detected only in the spleen of up to
      60% chicks at 2-4 weeks and in one chick at 3 weeks, respectively. The survey of
      three commercial Lohmann flocks, kept in biosecurity conditions, revealed the
      vaccine virus only in the spleen of 40% of 30-day-old chicks. The present study
      shows that CV1988 DNA is present in vaccinated chicks in a low quantity and it is
      difficult to detect directly from the chick, probably because vaccine viruses are
      latent in vivo. For an efficient detection it is pertinent to cultivate the
      vaccine virus on chicken embryo fibroblasts (CEF), as then the virus escapes the
      latent state, enters into the productive mode of replication, and a high viral
      copy number is produced.

PMID- 12002425
TI  - Diagnosis of Mycobacterium bovis infection in calves sensitized by mycobacteria
      of the avium/intracellulare group.
AB  - Because of the frequent exposure of cattle to mycobacteria of the
      avium/intracellulare group, an investigation was carried out into the possible
      repercussions thereof on the diagnosis of bovine tuberculosis. Three calves from
      a bovine tuberculosis-free herd, scored avian reactors in the gamma-interferon
      assay for bovine tuberculosis, were sedated and inoculated endotracheally with a
      virulent Mycobacterium bovis strain. Then, three other avian reactors were housed
      with the above donor calves. Mycobacterium bovis was isolated from the nasal
      swabs of the three endotracheally infected, donor calves. On these samples, TB
      complex-specific polymerase chain reaction (PCR) tests for IS6110 were also
      positive, albeit with a different time kinetics. The three contact-infected
      calves showed clear immunological signs of infection; however, their nasal swabs
      were always PCR-negative and only Mycobacterium avium was isolated. In the
      endotracheally infected donor calves there was a rise of the gamma-interferon
      responses to avian and bovine purified protein derivative (PPD) tuberculins,
      which reached the same stable plateau levels over the whole experiment. The above
      effect was also observed in the contact-infected calves, even though the response
      to avian PPD tuberculin always remained at a higher level. By using conventional
      bovine and avian PPD tuberculins, the comparative intradermal test was generally
      positive in endotracheally infected, as opposed to contact-infected calves; a
      positive intradermal test for M. bovis was obtained in two contact-infected
      calves by different bovine PPD tuberculins based on M. bovis bacillus Calmette
      Guerin (BCG) secreted or somatic antigens. It was concluded that M. bovis
      infection may be concealed for some time in cattle sensitized by mycobacteria of
      the avium/intracellulare group and that different diagnostic procedures should be
      adopted for such animals.

PMID- 12002426
TI  - Experimental mixed infection of rabbits with Yersinia enterocolitica and Listeria
      monocytogenes.
AB  - Experimental mixed infection was reproduced in rabbits after per os infection
      with Yersinia enterocolitica serotype 0:3 cells. Four days later some of animals
      were re-infected orally with Listeria monocytogenes serotype 4b cells. A third
      group of healthy rabbits was also infected per os with Listeria monocytogenes.
      The infectious process was followed dynamically from days 1-28. The experimental
      animals were examined for clinical, paraclinical and morphological findings.
      Augmentation of body temperature and alveolar macrophage number, a decreased
      number of peritoneal macrophages, leucopenia as well as purulent
      meningoencephalitis, catarrhal pneumonia, lienitis, lymphadenitis and enteritis
      were detected after experimental mixed infection. Both types of macrophages
      demonstrated a weak bactericidal activity against Yersinia enterocolitica and a
      highly expressed killing effect against Listeria monocytogenes. Yersinia and
      Listeria cells were isolated from the viscera and brain. Both species of bacteria
      were established intracellularly in the macrophages by electron-microscopic
      examination. The data received showed that mixed Yersinia enterocolitica 0:3 and
      Listeria monocytogenes 4b infection of rabbits runs with transitory hyperthermia
      as a generalized infection and is similar to the Listeria mono-infection. The
      immunosuppressive effect induced by oral Yersinia enterocolitica infection of
      rabbits promotes the expression of listerious agents.

PMID- 12002427
TI  - The evaluation and management of the azoospermic patient.

PMID- 12002428
TI  - Zona pellucida and progesterone-induced Ca2+ signaling and acrosome reaction in
      human spermatozoa.

PMID- 12002429
TI  - If it looks like a clone and acts like a clone, is it not a clone?

PMID- 12002430
TI  - Detection of differences in fertility.

PMID- 12002431
TI  - Peripheral benzodiazepine binding sites/receptors (PBRs) have been localized to
      rat central and peripheral endocrine tissues.

PMID- 12002432
TI  - Another piece in the maddening puzzle of declining steroidogenesis in aging
      Leydig cells.

PMID- 12002433
TI  - From Androlog.

PMID- 12002434
TI  - Efficacy of vardenafil and sildenafil in facilitating penile erection in an
      animal model.
AB  - Vardenafil and sildenafil are potent and specific phosphodiesterase type 5 (PDE
      5) inhibitors. In human penile cavernosal smooth muscle cells, we have previously
      shown that vardenafil has a lower biochemical inhibition constant (Ki) than
      sildenafil. In this study, we compared the efficacy of vardenafil and sildenafil
      in facilitating penile erection in a rabbit model. Penile erections were elicited
      by submaximal (2.5 or 6 Hz) pelvic nerve stimulation (PNS) repeated every 5
      minutes for 30 minutes with or without intravenous (i.v.) administration of
      vardenafil (1-30 microg/kg) or sildenafil (10-30 microg/kg). Erectile response
      was assessed by continuously recording intracavernosal pressure (ICP) and
      systemic arterial pressure (SAP). All data were expressed as a ratio of ICP:SAP.
      I.v. administration of either PDE 5 inhibitor facilitated PNS-induced erection
      and increased ICP:SAP in a dose-dependent manner, reaching peak response at
      approximately 5 minutes. However, the threshold dose at which facilitation of
      erection occurred was lower for vardenafil (3 microg/kg) than for sildenafil (10
      microg/kg). At the 10-microg/kg dose (i.v.), the response duration was
      significantly greater with vardenafil (169 +/- 23 seconds) than with sildenafil
      (137 +/- 31 seconds). Direct intracavernosal (i.c.) injection of 1-30 microg/kg
      vardenafil or sildenafil also caused dose-dependent increases in ICP:SAP in the
      absence of PNS. Response durations increased in a dose-dependent manner and
      lasted more than 5 times that of i.v. drug administration coupled with PNS.
      Irrespective of the route of administration (i.c. or i.v.), at equivalent doses,
      vardenafil was significantly more efficacious than sildenafil in facilitating
      pelvic nerve-mediated penile erection and in eliciting erection in the absence of
      PNS. The increases in ICPs occurred more quickly, were of larger magnitude, and
      were sustained for longer durations for vardenafil than for sildenafil. On the
      basis of the biochemical data and physiological responses from this study,
      further clinical evaluation of vardenafil as treatment for erectile dysfunction
      is warranted.

PMID- 12002435
TI  - Effect of carboplatin on the functional integrity of the human sperm membrane in
      vitro.
AB  - Although it is well known that carboplatin is a drug that binds directly to DNA,
      causing DNA-DNA and DNA-protein cross-links, which is the presumptive method for
      killing cells, the whole mechanism of action of carboplatin on spermatozoa is
      unclear. There are no published data in peer-reviewed journals focused on the
      interaction between carboplatin and cell membranes. Therefore, the purpose of
      this study was to investigate the minimal concentration of carboplatin that would
      affect the functional integrity of the human sperm membrane in an in vitro model.
      Human-ejaculated spermatozoa were obtained from 20 healthy normozoospermic
      donors. Solutions (SOL) of 0.5 mL of the semen samples and 0.5 mL NaCl (0.9%)
      containing increasing concentrations (7.5, 15, 30, and 60 ng) of carboplatin per
      1 mL of SOL were prepared. Then, the hypoosmotic-swelling (HOS) test and the
      eosin test were performed on these samples and compared with the control (no
      carboplatin) group. Significant damage to the plasma membrane in the head region
      (eosin test positive) and in the tail region of spermatozoa, as assessed by the
      HOS test, was observed in concentrations of 30 and 60 ng carboplatin per 1 mL of
      SOL in comparison to the values evaluated in the control group. The results
      demonstrate that a minimal carboplatin concentration of 30 ng/mL causes
      significant damage to membrane integrity of spermatozoa in healthy volunteers.

PMID- 12002436
TI  - Changes in hormone sensitivity in the ventral prostate of aging Sprague-Dawley
      rats.
AB  - The adult rat ventral prostate, which has been used extensively as a model for
      hormone-dependent prostate cancer, is composed of hormone-dependent columnar
      secretory epithelial cells and a mixture of hormone-independent cuboidal
      epithelial cells, basal epithelial cells, and stromal cells. Androgen ablation
      causes the gland to regress due to the selective loss of the secretory luminal
      epithelial cells that undergo apoptosis. Most, if not all, of the studies
      examining the induction of apoptosis and the mechanism of regression have used
      young adult males at around 3 months of age. Prostate cancer, however, is a
      disease of older males, and we have therefore investigated whether age-related
      changes in hormone sensitivity and apoptosis occur in the ventral prostate of
      aged animals (12 months old) compared to young animals (3 months old). We have
      observed distinct differences in the morphology of the prostate between young and
      old rats prior to castration and a significant slowing in the rate of regression
      after castration in older animals. These changes are accompanied by changes in
      lipofuscin accumulation and levels of the antioxidant enzymes catalase and
      manganese (Mn) superoxide dismutase in the gland.

PMID- 12002437
TI  - Capacitation and induction of the acrosome reaction in bull spermatozoa with
      norepinephrine.
AB  - Identification of norepinephrine (NE) within the microenvironment of the bovine
      oviduct suggests a potential role for catecholamines in the events surrounding
      fertilization. Previous studies have shown that the catecholamines capacitate and
      induce the acrosome reaction in spermatozoa from several species. The current
      project was undertaken to investigate the role of catecholamines in bovine sperm
      capacitation and the acrosome reaction. Freshly ejaculated bovine spermatozoa
      were incubated in NE (0-1000 ng/mL) and induced to acrosome-react with
      lysophosphatidylcholine (LPC). Additionally, spermatozoa capacitated with heparin
      were incubated with NE (0-1000 ng/mL) to assess its ability to induce the
      acrosome-reaction in capacitated spermatozoa. Concentrations of NE were chosen on
      the basis of physiological concentrations previously determined for bovine
      oviductal fluid. NE at concentrations of 10 and 20 ng/mL capacitated bovine
      spermatozoa after 2 hours of incubation. Additionally, spermatozoa incubated for
      2 hours with heparin were induced to acrosome-react with 10 and 20 ng/mL NE.
      Interestingly, higher concentrations of NE inhibited both capacitation and the
      acrosome reaction. Incubating spermatozoa with dopamine or epinephrine did not
      result in capacitation or the acrosome reaction, suggesting that the action of NE
      was specific to that catecholamine. The ability of NE to capacitate or induce the
      acrosome reaction appears to be dependent on the presence of another membrane
      destabilizing factor. Although adrenergic receptors have not been identified on
      spermatozoa from any species, the action of NE on spermatozoa may be a receptor
      mediated event. This study suggests a possible function for oviductal
      catecholamines in sperm preparation prior to fertilization.

PMID- 12002438
TI  - Expression and regulation of aquaporins 1, 8, and 9 in the testis, efferent
      ducts, and epididymis of adult rats and during postnatal development.
AB  - Aquaporins (AQPs) are membrane protein channels that allow the rapid passage of
      water through an epithelium containing tight junctions. In the present study,
      light microscope immunocytochemistry was utilized to localize several members of
      the AQP family in the testis, efferent ducts, and epididymis of normal adult
      animals during postnatal development and after various experimental procedures on
      adult animals. In the testis of normal adult animals, AQP-8 was expressed
      exclusively in Sertoli cells, while AQP-9 outlined Leydig cells. In the efferent
      ducts, AQP-1 was expressed on the microvilli, basolateral plasma membranes, and
      apical endosomes of the nonciliated cells and cilia of ciliated cells, while AQP
      9 was present only on the microvilli of nonciliated cells. In the epididymis, AQP
      9 was localized to the microvilli of the principal cells of all regions, with the
      most intense reaction being noted in the initial segment and cauda regions. The
      clear cells of the cauda region expressed only AQP-9. AQP-1 was not expressed in
      the testis or the epididymal epithelium, but it was expressed over the
      endothelial cells of the vascular channels of the efferent ducts and epididymis.
      After efferent duct ligation or orchidectomy, there was no change in the
      expression of AQP-1 or -9 over the microvilli or cilia of epithelial cells in the
      case of the efferent ducts, suggesting that testicular factors do not regulate
      their expression in this region. In contrast, AQP-9 expression in the principal
      cells of the initial segment, but not of other regions, and also in the clear
      cells of the cauda region was dramatically reduced after both treatments. As the
      expression was not restored to control levels by testosterone replacement, the
      data suggest that a luminal factor(s) derived from the testis regulates AQP-9
      expression in the principal cells of the initial segment and in the clear cells
      of the cauda region. Postnatal studies revealed that the expression of AQP-1 and 
      9 in the different cell types of the efferent ducts and epididymis occurred
      between days 7 and 29, eliminating sperm and high androgen levels as possible
      regulating factors. Taken together, these data suggest cell specificity with
      respect to the expression of AQP-8 and -9 in the testis. In the efferent ducts
      and epididymis, specificity exists in cell, region, and tissue distribution with
      respect to the expression of AQP-1 and -9, and their expression does not appear
      to be regulated by androgens.

PMID- 12002439
TI  - Segment-specific decrease of both catecholamine concentration and
      acetylcholinesterase activity are accompanied by nerve refinement in the rat
      cauda epididymis during sexual maturation.
AB  - In the present work, histochemical and biochemical studies were conducted to
      analyze changes in the pattern of autonomic innervation during sexual maturation,
      using the rat epididymis as a model. Glyoxylic acid histochemistry and
      immunohistochemical studies against dopamine beta-hydroxylase (DbetaH) and
      acetylcholinesterase (AChE) indicated a reduction in the amount of
      catecholaminergic and AChE-positive neurons, fibers, and puncta detected in the
      cauda epididymis of adult rats (120 days old), when compared to immature (40
      days) and young adult (60 days) animals. No obvious age-related variations were
      detected in the few catecholaminergic and AChE-positive fibers and puncta present
      in the caput region. AChE-positive fibers were found sorting out among epithelial
      cells and ending free upon the epithelial surface or into the tubular lumen of
      the cauda region of adult rats. Furthermore, a positive staining for AChE in
      epithelial cells was also detected in the caput and cauda epididymis in all ages
      studied. Biochemical analysis confirmed a significant decrease in noradrenaline
      concentration as well as AChE activity in the cauda epididymis with sexual
      maturation. Immunohistochemical studies against microtubule-associated protein 1B
      (MAP 1B), a neuronal cytoskeletal marker, further substantiated the quantitative
      changes observed in catecholaminergic and AChE-positive neuronal elements in the
      cauda epididymis. Thus, our results documented segment-specific variations in
      noradrenaline concentration and AChE activity during epididymal sexual maturation
      and suggest that such variations result, at least in part, from the refinement of
      the autonomic innervation pattern with age.

PMID- 12002440
TI  - Lipid diffusion in the plasma membrane of mouse spermatozoa: changes during
      epididymal maturation, effects of pH, osmotic pressure, and knockout of the c-ros
      gene.
AB  - It is well known that the plasma membranes of mammalian spermatozoa undergo
      extensive remodeling during maturation in the epididymal duct. In this
      investigation, we have used fluorescence recovery after photobleaching (FRAP)
      techniques to: 1) measure rates of lipid diffusion in the plasma membrane of
      mouse spermatozoa at different stages of maturation; 2) examine the effects of
      varying external conditions found in the epididymal duct (pH, temperature, and
      osmotic pressure) on lipid diffusion in mature sperm; and 3) investigate the
      effects of the c-ros null mutation that causes tail angulation in cauda
      spermatozoa after ejaculation as a result of cell swelling due to altered
      membrane function. Our results show that lipid diffusion (as measured using
      reporter probes 5-(N-octadecanoyl)aminofluorescein [ODAF] and 2-(6-(7-nitrobenz-2
      oxa-1,3-diazol-4-yl)amino)hexanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine
      [NBD-C6-PC]) is several times faster across the membrane on the sperm head than
      on the tail and that it increases significantly during passage from caput to
      cauda. Temperature variations between 20 degrees C and 37 degrees C have a
      substantial effect on diffusion coefficients, with the sperm head being more
      responsive than the tail. Changes in external pH (6.5-8.5) or osmotic pressure
      (202-389 mOsm/kg), however, have little relative effect on lipid diffusion on any
      region of the sperm. The rate of diffusion of 22-(N-(7-nitrobenz-2-oxa-1,3-diazol
      4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol) is 10-fold higher
      across the head plasma membrane than across the tail and does not change
      significantly during epididymal maturation. Similarly, lipid diffusion in hairpin
      shaped cauda sperm from c-ros (-/-) males is not significantly different from
      (+/+) controls. These results suggest that temperature and compositional changes
      are 2 of the important factors that regulate the dynamics of lipid molecules in
      the mouse sperm plasma membrane.

PMID- 12002441
TI  - Altered growth factor expression in the aging penis: the Brown-Norway rat model.
AB  - The objective of the present study was to evaluate age-related changes in the
      protein and gene expression of modulators of erectile function (nitric oxide [NO]
      and endothelin-1 [ET-1]) and growth factors such as transforming growth factor
      (TGF-beta1) and vascular endothelial growth factor (VEGF) in the penile tissue of
      Brown-Norway (BN) rats. Young and old BN male rats were euthanized, and the
      penile tissue was processed for immunohistochemical and molecular analyses. Total
      RNA was extracted, and an Access reverse transcription-polymerase chain reaction
      (RT-PCR) system was used for messenger RNA (mRNA) expression analysis.
      Immunohistochemical studies showed a decreased expression of endothelial nitric
      oxide synthase (eNOS) protein and an increased staining for ET-1. Quantitative
      analysis of PCR products revealed decreased levels of VEGF mRNA expression in the
      old population of rats. The most significant decrease was detected between bands
      corresponding to splice forms 164 (21%) and 120 (18%). The observed alterations
      in the gene expression of growth factors such as VEGF may contribute to the
      abnormal age-related morphological and physiological alterations in the erectile
      tissue.

PMID- 12002442
TI  - Peptide and nonpeptide reactive oxygen scavengers provide partial rescue of the
      testis after torsion.
AB  - Ischemia-reperfusion (IR) of the testis results in germ cell-specific apoptosis,
      followed by a reduction in testis weight and daily sperm production (DSP). This
      has been associated with an increase in the adhesion of neutrophils to testicular
      subtunical venules and an increase in reactive oxygen species (ROS). The present
      study investigated: 1) the effects of a direct, non-IR-related ROS insult to the
      testis and 2) the effects of catalase, superoxide dismutase (SOD), and a novel
      nonpeptide mimic of SOD, M40403, on neutrophil recruitment, ROS production,
      testis weight, and DSP following IR of the rat testis. Results revealed that the
      infusion of H2O2 increased testicular lipid peroxidation 1 hour after
      administration and increased germ cell apoptosis within 24 hours of
      administration. Four hours after the repair of torsion plus vehicle infusion,
      there was a significant increase in myeloperoxidase (MPO) activity, an indicator
      of neutrophil accumulation, and thiobarbituric acid reactive substances (TBARS),
      a measure of ROS production, compared to equivalent data in sham-treated testes.
      Animals sacrificed 30 days after the torsion plus vehicle infusion revealed a
      significant decrease in testis weight and DSP compared to the same parameters in
      sham-operated animals. The treatment of animals with catalase plus SOD or M40403
      showed a significant decrease in MPO activity and TBARS 4 hours after IR of the
      testis. Animals treated with SOD, SOD plus catalase, and M40403 provided a
      partial rescue of DSP 30 days after IR of the testis. These results demonstrate
      that oxidative stress can directly cause germ cell apoptosis, even outside the IR
      model, and confirm the importance of oxidative stress in testicular IR injury.
      Also, following testicular IR, there is a recruitment of neutrophils and an
      increase in ROS production in the testis. The administration of ROS scavengers
      significantly reduced the IR-induced responses. Interestingly, the administration
      of all ROS scavengers also blocked neutrophil recruitment to the testis. The
      mechanism by which ROS modulates neutrophil adhesion to venules is presently
      under investigation, as are additional therapeutic regimens to block oxidative
      stress.

PMID- 12002443
TI  - Identification of candidate genes involved in gonocyte development.
AB  - Several germ cell tumors that occur in adult men likely originate from gonocytes
      that are impaired in their development. To select candidate genes that are
      involved in the normal development of the gonocytes, we constructed a
      complementary DNA (cDNA) library from rat gonocytes as well as from single,
      paired, and aligned A spermatogonia (A(s), A(pr), and A(all) spermatogonia,
      respectively), their direct descendants. Five hundred gonocyte clones were
      differentially screened using both libraries. Successive verification by dot blot
      assays yielded 7 clones that were consistently highly abundant only in the
      gonocyte cDNA library. Also, in situ hybridization of these clones confirmed
      their differential expression. They encoded for, respectively, succinate
      dehydrogenase, ribosomal protein S15a, and the 65-kilodalton scaffolding subunit
      (a isoform) of protein phosphatase 2A. No clues regarding the nature of the
      remaining four clones could be found. Hence, using differential screening on both
      constructed cDNA libraries, we were able to select several genes that are
      interesting candidates for studying the molecular mechanisms of normal gonocyte
      development.

PMID- 12002444
TI  - Treatment of male hypogonadism with testosterone undecanoate injected at extended
      intervals of 12 weeks: a phase II study.
AB  - This paper reports the result of an open-label, non-randomized clinical trial
      investigating the efficacy and safety of an injectable preparation of
      testosterone undecanoate (TU) dissolved in castor oil and given over a 3.2-year
      period. In a previous study we demonstrated that injections of TU every 6 weeks
      resulted in satisfactory substitution but a tendency toward testosterone
      accumulation. Here we investigate prolonged TU treatment at extended injection
      intervals in 7 hypogonadal men. Injections were given at gradually increasing
      intervals between the fifth and 10th injection, and from then on every 12 weeks.
      Steady state kinetics were obtained after the 13th injection. Well-being, sexual
      activity, clinical chemistry, prostate volume, and prostate-specific antigen
      (PSA) and serum hormone levels were monitored. Patients were clinically well
      adjusted throughout the study. Before the next injection, testosterone,
      dihydrotestosterone, and estradiol levels were mostly within the normal range and
      showed a tendency to decrease with increasing injection intervals. Body weight,
      hemoglobin, serum lipids, PSA, and prostate volume did not change significantly
      during the 3.2 years of treatment. PSA levels were always within the normal
      limit. Maximal testosterone levels during steady state kinetics were measured
      after 1 week with 32.0 +/- 11.7 nmol/L (mean +/- SD). Before the last injection,
      mean testosterone concentrations were 12.6 +/- 3.7 nmol/L. Compared with
      conventional testosterone enanthate or cypionate treatment requiring injection
      intervals of 2-3 weeks and resulting in supraphysiological serum testosterone
      levels, injections of TU at intervals of up to 3 months offer an excellent
      alternative for substitution therapy of male hypogonadism.

PMID- 12002445
TI  - Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive
      antimicrobial agent.
AB  - The spread of sexually transmitted infections (STIs) and limited methods for
      control of pregnancies presents high risks to the reproductive health of women.
      Methods controlled by women and directed toward disease prevention and
      contraception are needed. We report on preclinical studies of the biological
      properties of sodium cellulose sulfate (Ushercell) currently being developed for
      use as a topical contraceptive antimicrobial agent. Ushercell was evaluated with
      tests designed to identify its contraceptive and antimicrobial properties.
      Ushercell inhibits hyaluronidase (reversible; IC50 = 1.7 mg/mL), impairs sperm
      penetration of cervical mucus (approximately 70% inhibition at 1 mg/mL), and acts
      as a stimulus for acrosomal loss (IC50 = 52 ng/mL). It prevents conception in
      rabbits when added to spermatozoa (approximately 95% inhibition at 1 mg/mL) or
      when vaginally applied (complete contraception by 45 mg) before insemination.
      However, up to 50 mg/mL, Ushercell does not irreversibly immobilize spermatozoa,
      suggesting that Ushercell is not cytotoxic. Ushercell has a broad spectrum of
      antimicrobial activity in vitro. Inhibited microbes include human
      immunodeficiency viruses (different laboratory strains and clinical isolates;
      IC50 values range from 3 to 78 microg/mL), herpes viruses, HSV-1 (IC50 = 59
      ng/mL) and HSV-2 (lC50 = 24 ng/mL), Neisseria gonorrhoeae (IC50 = 2 microg/mL),
      and Chlamydia trachomatis (IC50 = 78 microg/mL). In contrast, Ushercell does not
      inhibit growth of beneficial vaginal bacteria, Lactobacillus gasseri, at 5 mg/mL.
      These results suggest that the antimicrobial effects of Ushercell are selective,
      and not likely mediated by nonspecific cytotoxic mechanisms. These data provide
      the basis for further clinical development of Ushercell as a vaginal agent to
      prevent unplanned pregnancy and STIs.

PMID- 12002446
TI  - Cholesterol transport, peripheral benzodiazepine receptor, and steroidogenesis in
      aging Leydig cells.
AB  - The cellular mechanisms responsible for age-related decline in the ability of
      Leydig cells to produce testosterone are not yet fully understood. The decline in
      testosterone production could result from a reduction in the Leydig cell
      enzymatic activities mediating testosterone synthesis, the amount of substrate
      available for these enzymes, or both. In the present study, we examined the
      effect of age on a critical early step in the steroidogenic pathway, the
      transport of cholesterol into mitochondria. Leydig cells were isolated from the
      testes of young and old Brown Norway rats and incubated with human chorionic
      gonadotropin (hCG) and the side-chain cleavage cytochrome P450scc inhibitor
      aminoglutethimide (AMG). Mitochondria were isolated from these cells in the
      presence of AMG. Upon removal of AMG, the mitochondria from old cells produced
      80% less steroid than those from young cells, only a fraction of which could be
      accounted for by a decrease in P450scc activity. These results suggest that the
      accumulation of hormonally recruited cholesterol into mitochondria is defective
      in old Leydig cells. With this in mind, we turned our attention to peripheral
      benzodiazepine receptor (PBR), a mitochondrial cholesterol-binding protein known
      to be involved in mediating cholesterol transport. PBR messenger RNA (mRNA) and
      protein expression were decreased in old cells. Moreover, both the dissociation
      constant (Kd) and the number of binding sites (Bmax) of the PBR were decreased in
      the old cells by 50% and 30%, respectively. Taken together, these results suggest
      that alterations in cholesterol transport and in PBR may play critical roles in
      age-related decreases in testosterone production in Brown Norway rat Leydig
      cells.

PMID- 12002447
TI  - Effects of selected metal oxides on the dechlorination and destruction of PCDD
      and PCDF.
AB  - OCDD and OCDF spiked silica/graphite based model fly ash containing various
      copper compounds and metal oxides were thermally treated under oxygen deficient
      conditions. All copper compounds tested showed a considerable
      dechlorination/hydrogenation reaction at 260 degrees C. After 30 min at 340
      degrees C, less than 1% of the spiked OCDD and OCDF was recovered as T4CDD/F to
      OCDD/F. Other compounds tested demonstrated a lower rate of dechlorination
      compared to the copper compounds. However, all other metal oxides showed a small
      dechlorination effect at 260 degrees C, which was considerably increased at 340
      degrees C. The model fly.ash containing the different copper compounds or metal
      oxides showed comparable PCDD and PCDF isomer patterns after thermal treatment.
      However, small differences were observed among the different tested compounds.
      The PCDD and PCDF isomer patterns on the model fly ashes were similar to patterns
      found during dechlorination experiments on fly ashes from waste incineration
      processes. Model fly ash containing Ca(OH)2 exhibited the highest destruction
      potential, but a low dechlorination potential. In contrast, model fly ash
      containing any of the remaining compounds tested, was found to predominantly
      dechlorinate the spiked OCDD and OCDF.

PMID- 12002448
TI  - Dechlorination and destruction of PCDD, PCDF and PCB on selected fly ash from
      municipal waste incineration.
AB  - The potential of fly ash to dechlorinate and destroy PCDD, PCDF and PCB was
      tested under oxygen deficient conditions in the laboratory. Specifically, two
      types of fly ash were compared, originating either from a fluidized bed
      incinerator using Ca(OH)2 spray (FA1), or a stoker incinerator without Ca(OH)2
      impact (FA2). Results from the present study indicate that on FA2 type fly ash,
      the degradation processes of OCDD, OCDF and D10CB occurred primarily via
      dechlorination/hydrogenation up to temperature settings of 340 degrees C. In
      contrast, FAI type fly ash was found to effect both dechlorination and
      destruction of these compounds already at temperature settings of 260 degrees C.
      The dechlorination velocity of PCDD and PCDF did not differ significantly.
      However, the first dechlorination step of OCDF in the 1,9-position occurred
      faster compared to the first dechlorination step of OCDD. The isomer pattern
      resulting from the dechlorination processes was quite similar on both FAI and
      FA2, indicating that differences in alkalinity or elemental composition of the
      two types of fly ashes do not have a significant influence on the position of
      dechlorination. PCDD and PCDF dechlorination of the 2,3,7,8-positions was not
      favoured over dechlorination of the 1,4.6,9-positions on either type of fly ash.
      In contrast, dechlorination of PCB occurred predominantly on the toxicological
      relevant 3- and 4-positions. The dechlorination/destruction processes were
      completed on both types of fly ash at 380 degrees C within one hour, which
      correlates well with results obtained from actual plant operation practices.

PMID- 12002449
TI  - Formation and destruction of PCDD/F inside a grate furnace.
AB  - Formation and destruction of polychlorinated dibenzo-p-dioxins and dibenzofurans
      PCDD/F during the combustion process was investigated experimentally in a pilot
      plant. All important process steps like the burnout of the fuel bed on the grate,
      the burnout of the flue gas inside the combustion chamber, the heat recovery in a
      boiler as well as influences of the fuel composition are described in detail.
      High concentrations especially of PCDF are formed during the burnout of the fuel
      bed. The formation reaction is mainly influenced by the fuel composition and the
      burnout characteristic of the fuel bed. Fuels with low chlorine and low metal
      content (Cu) result only in negligible concentrations of PCDD/F. Under stable
      combustion conditions characterized by an excellent flue gas burnout PCDD/F will
      almost be completely destroyed already inside the combustion chamber. "Cold
      strands" of unburned flue gas (high CO concentrations) caused by disturbed
      combustion conditions will result in high concentrations of PCDD and especially
      of PCDF in the raw gas. A second place of PCDD/F formation is the well-known
      boiler section. Here fly ash deposits containing residual carbon (mainly soot
      particles) are the source for the formation reaction. Under stationary effective
      combustion conditions, they are dominant for PCDD/F concentrations in the raw gas
      over a very long period of time. Stationary efficient flue gas burnout
      (especially soot) together with effective boiler cleaning will guaranty low
      concentrations of PCDD/F in the flue gas in front of the flue gas cleaning
      system.

PMID- 12002450
TI  - Radical/radical vs radical/molecule reactions in the formation of PCDD/Fs from
      (chloro)phenols in incinerators.
AB  - Pathways from chlorinated phenols as precursors to PCDD/Fs are discussed with
      focus on the effect of (poly)chlorination on thermochemistry and rate in the
      displacement of chlorine from a chlorophenol molecule by a (chloro)phenoxy
      radical (reaction (A) as a key example). Through measurements on the respective
      methylethers (anisoles) the O-H bond of 2,4,6-TCP turns out to be 5 kcal/ mol,
      and that in PCP 4 kcal/mol, less strong than O-H in phenol itself. On this basis
      it is concluded that-in contrast with earlier proposals--displacements such as in
      reaction (A) are at least as slow as reaction (B) of phenoxy radical with
      chlorobenzene. PhO. + PhCl -->PhOPh + Cl. reaction B Compared with condensation
      of two (chloro)phenoxy radicals, such radical/molecule reactions are therefore an
      insignificant pathway to dioxins in incinerators.

PMID- 12002451
TI  - Thermolysis of 2,4,6-trichlorophenol chemisorbed on aluminium oxides as example
      of fly ash mediated surface catalysis reaction in PCDD/PCDF formation.
AB  - The influence of aluminium cation as a strong electrophilic centre on the
      thermolysis of chlorophenols chemisorbed on Al(OH)3 surface was investigated. If
      thermolysis is carried out at 300 degrees C the spontaneous rupture of the bond
      between aluminium and oxygen of phenol takes place in the temperature range of
      260-280 degrees C. The thermolysis of chlorophenoxy aluminium compounds occurs
      through homolytic and heterolytic bond cleavage. In the case of heterolytic
      cleavage the leaving chlorophenoxy anion causes a simultaneous formation of the
      aluminium cation, which is the driving force for the rearrangement of the
      unstable intermediate. By homolytic cleavage of the Al-O bond the chlorophenoxy
      radical is formed. The isolation of reaction products of the thermolysis of the
      system AI(OH)3/2,4,6-trichlorophenol gave five isomers of dimeric compounds of
      resonance stabilised 2,4,6-trichlorophenoxy radical. The compounds are stable in
      nonaqueous, aprotic solution, but they are very sensitive to acid catalysis. They
      quickly transform into aromatic hydroxydiphenyl ethers. The process of
      dechlorination and aromatisation of cyclohexadienone dimers gives PCDD/PCDF.

PMID- 12002452
TI  - Predictions for isomer distributions of toxic dioxins and furans in selected
      industrial combustion processes.
AB  - Three thermodynamic databases of polychlorinated dibenzo-p-dioxins and dibenzo
      furans (PCDD/Fs) have been used to simulate the PCDD/F isomer distribution in
      industrial combustion processes. The three databases had been derived using the
      Group Additivity approach and two computational molecular modelling methods,
      Modified Neglect of Diatomic Overlap (MNDO) and Parametrized Model 3 (PM3),
      respectively. The predictions of the toxic PCDD/F isomer distributions using the
      three different databases have been compared with measured values from industrial
      processes. An excellent agreement between the predictions using the MNDO method
      and the measured data has been obtained. It is concluded that the PCDD/F isomer
      distributions within each group observed in these combustion processes may be
      thermodynamically controlled.

PMID- 12002453
TI  - Reductive dechlorination of polychlorinated dibenzo-p-dioxins by zerovalent iron
      in subcritical water.
AB  - A new method for reductive dechlorination of polychlorinated dibenzo-p-dioxins
      (PCDDs) and remediation of contaminated soils is described that uses zerovalent
      iron as the dechlorination agent and subcritical water as reaction medium and
      extractive solvent. It is found that the zerovalent iron can be applied for
      stepwise dechlorination of octachlorinated dibenzo-p-dioxin (OCDD) on various
      matrixes in subcritical water. By using iron powder as matrix higher chlorinated
      congeners were practically completely reduced to less than tetra-substituted
      homologues. A significant part of residual OCDD, when it was spiked in to soils,
      and formed less chlorinated congeners are extracted with water in the given
      conditions. The solubility of OCDD was increased by a 4-6 orders over its
      solubility at ambient conditions. The new method of contentious-flow extraction
      is described.

PMID- 12002454
TI  - Dibenzo-p-dioxins in the environment from ceramics and pottery produced from ball
      clay mined in the United States.
AB  - Processed ball clay samples used in the production of ceramics and samples of the
      ceramic products were collected and analyzed for the presence and concentration
      of the 2,3,7,8-Cl substituted polychlorinated dibenzo-p-dioxins and -furans
      (PCDDs/PCDFs). The processed ball clay had average PCDD concentrations of 3.2
      ng/g toxic equivalents, a congener profile, and isomer distribution consistent
      with those found previously in raw ball clay. The PCDF concentrations were below
      the average limit of detection (LOD) of 0.5 pg/g. The final fired ceramic
      products were found to be free of PCDDs/PCDFs at the LODs. A consideration of the
      conditions involved in the firing process suggests that the PCDDs, if not
      destroyed, may be released to the atmosphere and could represent an as yet
      unidentified source of dioxins to the environment. In addition, the PCDDs in clay
      dust generated during manufacturing operations may represent a potential
      occupational exposure.

PMID- 12002455
TI  - Total TEQ emissions (PCDD/F and PCB) from industrial sources.
AB  - Flue gas samples from eight different sources (industrial plants and crematories)
      have been analyzed for PCDD/Fs and PCBs and total Toxicity EQuivalents (TEQ)
      values have been calculated using the latest WHO toxicity equivalent factors from
      1998. A contribution of PCBs to the Total TEQ up to 16% was found, within the 12
      WHO-PCBs PCB-126 contributes mostly to the TEQ. Thermodynamic stability of PCBs
      was calculated semiempirically using the MOPAC program package and differences in
      the heat of formation (HoF) were compared to the distribution of PCBs in real
      samples. Partial correspondence between fact and theory could be found.

PMID- 12002456
TI  - A research on dioxin generation from the industrial waste incineration.
AB  - By using fluidized-bed furnace and rotary-kiln+stoker furnace and four different
      kinds of industrial wastes such as waste wood, coffee mill, waste oils and waste
      plastics, we have drawn the following conclusions: (1) A relationship between
      H6CBz and DXN is acquired, which is DXN = 0.34 x H6CBz(1.1) (2) The following
      means of emission reduction can be considered. (a) Reduction of DXN and Cl
      accumulation within the furnace, (b) control by the incinerated object, (c)
      control through the precursors of H6CBz, (d) improvement through operational
      control, (e) ammonia injection into the high-temperature zone of the furnace
      seems to be effective in reducing DXN and (f) DXN concentration is high with CO
      above 1,800 ppm, though it decreases with CO below approximately 10 ppm.

PMID- 12002457
TI  - PCDD/F mass balance in the flue gas cleaning units of a MSW incineration plant.
AB  - With the main purpose of evaluating PCDD/F presence and the corresponding mass
      balance over the emissions control system, an extensive study was performed on a
      municipal solid waste full scale incinerator equipped with a best available
      technology flue gas treatment line. Present paper reports the main results
      obtained, with particular reference to the PCDD/F concentration profiles and mass
      balances derived for every process unit of the flue gas control system. Total
      release evaluated for the plant is also outlined compared with data on PCDD/F
      content of raw waste and with reference values included in most recent
      guidelines.

PMID- 12002458
TI  - PCDD/F-contamination in a hexachlorocyclohexane waste site in Rio de Janeiro,
      Brazil.
AB  - In the 1950s, a production plant of hexachlorocyclohexane (HCH) was established
      in Brazil with the main purpose of producing chemicals for vectors control. This
      factory was closed down in 1955 and around 300 tons of production residues were
      left behind in the open air. In 1995, the area was treated with lime to eliminate
      the HCH contamination. Soil sample gave a PCDD/F concentration of 13,900 ng I
      TEQ/kg whereas samples from the neighborhood ranged from 0.19 to 2.08 ng I
      TEQ/kg. PCDD/F levels in cow's milk samples varied from 4.1 to 6.5 pg I-TEQ/g of
      milk fat. High concentration in soil collected from the site suggests that
      treatment and recovery shall be made. Further dioxin monitoring is needed to
      better estimate the risk posed to local population through food consumption and
      soil usage.

PMID- 12002459
TI  - Investigations into the PCDD contamination of topsoil, river sediments and
      kaolinite clay in Queensland, Australia.
AB  - Recent findings of elevated PCDDs from an unknown source in the coastal marine
      environment of Queensland, Australia has instigated further investigations into
      the distribution of, and environments associated with the PCDD contamination.
      This study presents data for OCDD concentrations in the coastal, mountainous and
      inland environment of Queensland. Additionally, full 2,3,7,8-substituted
      polychlorinated dibenzo-p-dioxins and dibenzofuran (PCDD/F) profiles from
      different land-use types and environments in the coastal region were analysed.
      Distinct east-west gradients were detected in topsoil collected from various
      bushland regions with elevated OCDD concentrations confined to the coastal
      region. However, PCDD/F results from topsoil and river sediments collected in the
      Queensland coastal region suggest that elevated OCDD concentrations cannot be
      attributed to any of the environments, land-use or industry types investigated.
      PCDD/F congener profiles from select samples were remarkably similar to those
      previously described in marine sediments collected along the entire Queensland
      coastline. In addition, kaolinite clay samples from Queensland exhibited elevated
      OCDD concentrations, and PCDD/F profiles in these samples were similar to those
      detected in kaolinite clays elsewhere. Natural formation processes have been
      hypothesised as the source of elevated PCDDs in Queensland and other locations,
      where similar PCDD/F profiles and the general lack of anthropogenic sources are
      evident. This study presents additional data supporting this hypothesis and
      provides further information that may assist in the identification of the
      processes involved in the natural formation of PCDDs.

PMID- 12002460
TI  - Baseline levels of PCDD/Fs in soil and herbage samples collected in the vicinity
      of a new hazardous waste incinerator in Catalonia, Spain.
AB  - The construction in Constanti (Catalonia, Spain) of a new hazardous waste
      incinerator (HWI), which is the first one in Spain, finished in 1999. In order to
      determine the temporal variation (1996-1998) in the concentrations of
      polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in the
      vicinity of the new HWI, 40 soil and 40 herbage samples were collected (1998) at
      the same sampling points in which samples had been taken two years before (1996).
      Each sample was analyzed for PCDDs and PCDFs by high resolution gas
      chromatography/high resolution mass spectrometry. In the 1996 survey, PCDD/F
      concentrations in soils ranged from 0.13 to 24.20 ngl-TEQ/kg (d.m.), with median
      and mean values of 0.67 and 1.68 ngl-TEQ/kg (d.m.), respectively. In the present
      study, PCDD/F concentrations ranged from 0.12 to 17.20 ng I-TEQ/kg (d.m.), with a
      median value of 0.75 ng I-TEQ/kg (d.m.) and a mean value of 1.59 ng I-TEQ/kg
      (d.m.). In turn, in the present study PCDD/F concentrations in vegetation ranged
      from 0.14 to 2.01 ng I-TEQ/kg(d.m.) (median and mean values: 0.23 and 0.31 ng I
      TEQ/kg, respectively), while in the 1996 survey PCDD/F concentrations ranged from
      0.24 to 1.22 ngl-TEQ/kg (d.m.) (median and mean values: 0.53 and 0.61 ng I
      TEQ/kg. respectively). According to the present (1998) and the previous (1996)
      levels of PCDD/Fs found in soils and vegetation, the area under potential
      influence of the new facility shows a rather low contamination by these
      compounds. The current results should be useful to establish the environmental
      impact of the HWI.

PMID- 12002461
TI  - Monitoring of air pollution by polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans of pine needles in Korea.
AB  - The atmospheric contamination levels of polychlorinated dibenzo-p-dioxins (PCDDs)
      and polychlorinated dibenzofurans (PCDFs) were evaluated from the analysis of
      pine needles in South Korea. Pine needles were collected from 30 sampling points
      at five main cities in South Korea (Busan, Daegu, Gwangju, Changwon and Jeju
      island). The highest concentrations of PCDDs/DFs (2.19-26.88 pg I-TEQ/g of dry
      weight) were measured at Busan. where is the city of the highest population
      density and traffic volume among five cities. The lowest concentration was
      detected at Jeju with 0.62 pg I-TEQ/g dry weight. suggesting Jeju could be an
      environmental background area in Korea. The dominant homologues of PCDDs/DFs in
      pine needles were the lower chlorine-substituted compounds such as tetra CDDs and
      CDFs, and the distribution ratios of PCDDs/DFs decreased with increase of the
      number of chlorine substituents. Homologue profiles of pine needle samples were
      similar to PCDDs/DFs profiles of the vapor phase in the ambient air, and thus the
      pine needles absorbed the vapor phase of PCDDs/DFs from air. Results suggested
      that pine needles could be used as an indicator of the atmospheric contamination
      for PCDDs/DFs in Korea.

PMID- 12002462
TI  - Examination of dioxin fluxes recorded in dated aquatic-sediment cores in the
      Kanto region of Japan using multivariate data analysis.
AB  - Past dioxin (coplanar polychlorinated biphenyl (Co-PCB), 2,3.7,8-substituted
      polychlorinated dibenzo-p-dioxin (PCDD) and 2,3,7,8-substituted polychlorinated
      dibenzofuran (PCDF)) fluxes recorded in dated aquatic-sediment cores were
      analyzed using principal component analysis (PCA). The data set consisted of
      samples from four cores collected from the Kanto region of Japan. Time trends and
      spatial differences in the dioxin flux were examined, and the potential
      relationship to emission sources was investigated. Twenty-five compounds and 58
      core slices, corresponding to the later half of the 20th century, were subjected
      to the analysis. The PCA of both log-transformed and maximum-value-standardized
      data successfully divided the dioxin compounds into a small number of groups, and
      three similar clusters of Co-PCBs. PCDDs and penta- to hepta-CDFs were
      identified. PCB formulations used in the past are judged to have been responsible
      for the major part of the Co-PCB flux recorded in the sediment cores. However,
      the relationship to emission sources needs further investigation. It is suggested
      that most 2,3,7,8-substituted PCDDs and PCDFs are different from Co-PCBs in their
      emission sources or movements in the environment. The subcore clusters obtained
      from the PCA of log-transformed data show that the cores from different sampling
      areas exhibited distinct dioxin fluxes and compositions. Common time trends among
      the cores were more effectively summarized by the PCA of maximum-value
      standardized data focusing on relative time trends. PC scores show that recently
      the flux of each dioxin compound in the four cores has been generally declining
      after having reached a peak.

PMID- 12002463
TI  - Why biota still accumulate high levels of PCB after removal of PCB contaminated
      sediments in a Norwegian fjord.
AB  - Accumulation of polychlorinated biphenyls (PCBs) in blue mussels (Mytilus edulis)
      and semipermeable membrane devices (SPMDs) was still high after the removal of
      PCB contaminated sediments from a Norwegian fjord by dredging. The accumulation
      of low chlorinated PCB congeners with a low octanol water-partitioning
      coefficient (K(ow)) in blue mussels and SPMDs was higher than for the highly
      chlorinated congeners with a high K(ow). The accumulation of low chlorinated
      congeners was also higher in a lightly contaminated area compared to a highly
      contaminated area. That dredging the contaminated sediments was unsuccessful in
      lowering PCB levels in the biota may be for the following reasons: (1) Due to the
      low solubility of PCBs in the water it is possible that a decrease in the
      sediment concentration of PCB would leave the water concentrations of PCB
      unchanged. (2) Removal of the fine organic sediments may also play an important
      role, since a seabed with coarse inorganic material has a lesser ability to bind
      PCB. (3) The dredging may whirl up fine contaminated particles that eventually
      settles on the seabed producing a thin contaminated sediment layer that determine
      the water concentration. (4) Bioaccumulation in blue mussels and in the SPMDs
      occurs mostly from PCB dissolved in the water column. Since the water
      concentration of PCB is unchanged by the dredging, the accumulation in SPMDs and
      mussels is the same as before dredging. Further monitoring need to be carried out
      to report the long-term effect of the dredging.

PMID- 12002464
TI  - Specific biomagnification of polychlorinated dibenzo-p-dioxins and dibenzofurans
      in tufted ducks (Aythya fuligula), common cormorants (Phalacrocorax carbo) and
      their prey from Lake Shinji, Japan.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/DFs) were detected in
      waterfowl such as common cormorants, tufted ducks, and their prey, namely fish
      and bivalves from Lake Shinji, Japan. The concentration of total PCDDs/DFs-TEQ
      was found to be higher in the muscle tissues of common cormorants than in those
      of tufted ducks. The results of hierarchical cluster analysis implied that the
      residue distribution pattern of PCDD/DF homologues was considerably different
      between these two species. Furthermore, biomagnification factors (BMFs) were
      estimated from bivalves as prey to tufted duck muscles as target organs. Despite
      the highest concentrations of 1,3,6,8- and 1,3,7,9-TeCDD in tufted ducks and
      their prey, however, the BMFs of these isomers were calculated to be lower than
      those of the toxic 2,3,7,8-substituted PCDDs/DFs. On the other hand, log BMF of
      toxic 2,3,7,8-substituted PCDDs/DFs were significantly higher for lower
      chlorinated isomers than those of the higher chlorinated isomers. The biota
      sediment accumulation factors (BSAFs) of PCDDs/DFs were also estimated using
      shijimi clam and fish samples against sediment from Lake Shinji. The average
      BSAFs were estimated and ranged from 4.0 x 10(-3) to 2.2 x 10(-1) and 2.0 x 10(
      4) to 2.0 x 10(-1) for bivalve and fish samples, respectively. Based on
      calculated BMFs and BSAFs, the total PCDD/DF-TEQ levels in the tufted duck were
      estimated to have been lowest (2.0 pg TEQ/g dry weight basis) in 1947 and highest
      (9.8 pg TEQ/g) in 1971.

PMID- 12002465
TI  - Size-related bioaccumulation and between-year variation of organochlorines in ice
      associated amphipods from the Arctic Ocean.
AB  - Organochlorines are found even in organisms living in remote areas such as the
      Arctic marginal ice zone. Organochlorine concentrations in ice-associated
      (sympagic) amphipods are related to their diet. Therefore, the size-dependent
      diet shift of Gamunarus wilkitzkii may influence its organochlorine content. In
      this preliminary study, the organochlorine concentrations in two size classes
      (small < or = 29 mm and large >29 mm) of G. wilkitzkii were analysed. The
      concentrations of more lipophilic compounds [e.g. polychlorinated biphenyls
      (PCBs)] were lower in the small than the large size class, whereas concentrations
      of less lipophilic compounds [e.g. hexachlorocyclohexanes (HCHs)] did not differ
      by size class. Since contamination transport by the atmosphere, ocean currents
      and sea ice may vary, the organochlorine burden in sympagic organisms may also
      vary. There are no data available on temporal variation of organochlorine burden
      in Arctic sympagic fauna. Therefore, we compared organochlorine concentrations in
      sympagic amphipods (G. wilkitzkii, Apherusa glacialis and Onisimus spp.) between
      1998 and 1999. Organochlorine concentrations in all amphipods were low in both
      years, with sum organochlorines from 50.7 to 621.9 ngg(-1) lipid weight. The
      concentrations of hexachlorobenzene (HCB), chlordanes, DDTs and PCBs were higher
      in 1999 than 1998, whereas the HCH concentrations were lower in 1999 than 1998.
      The organochlorine concentrations differed between the taxa in both years in a
      similar increasing manner from A. glacialis to both G. wilkitzkii and Onisimus
      spp In studies of bioaccumulation relative to body size and temporal variation, a
      thorough interpretation requires samples from several size classes and years.
      Nevertheless, the present data provide new knowledge on contaminants in Arctic
      invertebrates where data are scarce.

PMID- 12002466
TI  - A design of two simple models to predict PCDD/F concentrations in vegetation and
      soils.
AB  - The vegetation and soil levels of the 17 polychlorinated dibenzo-p-dioxin and
      dibenzofuran (PCDD/F) toxic congeners were calculated by means of a vegetation
      and a soil model, respectively. Both models predicted the levels of the 17 PCDD/F
      congeners in quite good agreement with the observed results although the soil
      model was more accurate than the vegetation model. Four different pathways of
      contribution to the vegetation concentrations were taken into account: vapour
      phase absorption, dry particle deposition, wet particle deposition and uptake by
      root. The most important pathway was the vapour-phase absorption and the less was
      the uptake by root. In the soils model four pathways were considered: background
      soil concentration, dry particle deposition, wet particle deposition and uptake
      by root. After the background concentration, the most important pathway was the
      wet deposition.

PMID- 12002467
TI  - Determination of PCDDs and PCDFs in different animal feed ingredients.
AB  - As result of a study to control feedstuff, analyses were carried out to evaluate
      the contamination caused by PCDDs and PCDFs in different animal feed ingredients.
      Thirty two samples were selected, including ingredients of animal and mineral
      origin. For samples of mineral origin, some additives widely employed as binder
      and anticaking agents, such as bentonite, damoline, kaolin, magnesite, sepiolite
      and zeolite were selected. And, for ingredients of animal origin, samples of
      hemoglobin, animal fat, fish oil, fish meal and meat and bone meal were analyzed.
      The levels ranged from 0.52 to 9.08 pg WHO-TEQ/g fat for samples of animal
      origin, and from 0.05 to 460.59 pg WHO-TEQ/g for samples of mineral origin. The
      higher concentrations were observed for the kaolin samples that presented high
      levels of dioxin contamination.

PMID- 12002468
TI  - Chlorinated components in lime used in production contaminated citrus pulp
      pellets from Brazil.
AB  - In order to further understand the contamination of the citrus pulp pellets (CPP)
      that were exported to Europe in 1997 we examined both contaminated lime and CPP
      samples for the distribution of polychlorinated biphenyls (PCBs) and chlorinated
      benzenes (tri-hexa). Standard isotope dilution techniques were applied for all
      samples, which were analysed by selected ion monitoring high resolution GC-MS.
      Lime that is used in the production of CPP product is highly contaminated with
      PCBs and chlorobenzenes.

PMID- 12002469
TI  - Lime as the source of PCDD/F contamination in citrus pulp pellets from Brazil and
      status of the monitoring program.
AB  - After an exhaustive investigation, in 1997 the source of the milk contamination
      in Germany was traced to citrus pulp pellets originating from Brazil. It has been
      shown that lime was the source of the PCDD/F contamination of these products.
      After this conclusion, a continuous monitoring program has been performed over a
      two year period and the results are presented in this paper. Standard isotope
      dilution techniques were used for all samples, which were analyzed by selected
      ion monitoring high resolution GC-MS.

PMID- 12002470
TI  - Comprehensive study on dioxin contents in binder and anti-caking agent feed
      additives.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) were determined in some additives widely employed as binder and anti
      caking agents in feedstuffs, such as kaolin, bentonite, zeolite, etc. with an
      special attention on sepiolite samples. Owing to their physico-chemical
      properties, the little information of these materials reported in the literature,
      the variability of PCDDs/PCDFs found in a preliminary evaluation and the absence
      of reference materials highlighted further research needed. Therefore, an
      extensive study on the analytical procedures based on the classical methods was
      performed with sepiolite samples. The study includes evaluation of
      reproducibility and repeatibility. To this end, a series of intra-day and nine
      inter-day analysis were made. The methodolgy was also assessed against the sample
      size and series of 12.5, 25, 37.5 and 50 g were analyzed. In all cases, the
      results confirmed good correlation with the parameters evaluated.

PMID- 12002471
TI  - Determining dioxin-like compounds in selected Korean food.
AB  - To measure the levels of dioxin-like compounds, pork, mackerel, cheese and milk
      were analyzed. The food samples were obtained at three different markets in
      Seoul. All the samples were animal origin and their lipid contents ranged from 4%
      to 34%. After extraction, extracts were cleaned up by sulfuric acid impregnated
      silica gel, purified on a series of silica gel, alumina, carbon column
      chromatography and then analyzed by high resolution gas chromatography/high
      resolution mass spectrometry. The levels of polychlorinated dibenzo-p
      dioxins/furans for pork, mackerel, cheese and milk were 0.0008, 0.8663, 0.002 and
      0.0236 pgTEQ/g wet weight, respectively. In addition, the levels of non-ortho
      coplanar polychlorinated biphenyls for pork, mackerel, cheese and milk were
      0.0041, 1.5781, 0.0259 and 0.0353 pgTEQ/g wet weight, respectively. Among food
      samples analyzed, pork showed the lowest level of dioxin-like compounds.

PMID- 12002472
TI  - PCDD/PCDF, chlorinated pesticides and PAH in Chinese teas.
AB  - Four samples of Chinese tea (two green teas, and two brick teas) were analyzed
      for their concentrations of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans (PCDD/PCDF), chlorinated pesticides and PAH. The infusions prepared
      from these teas were also analyzed for PCDD/PCDF. The levels of DDT and its
      metabolites in tea leaves were within the safety limit of 0.2 mg/kg. Rather high
      levels of total PAH were obtained in brick tea (1,048-1,162 mg/kg). when compared
      with green tea (497-517 mg/kg). In terms of PCDD/PCDF, the concentrations of
      green tea and brick tea differed by a factor of 16, while the concentrations of
      all infusions were within a factor of 2. The dioxin concentrations in green tea
      leaves can be explained through uptake of atmospheric PCDD/PCDF. The higher
      concentrations in the brick tea leaves are due the longer exposure time, and to
      certain extent, the use of old leaves, branches and roots when making the tea,
      and additional components such as soil particulates through contamination.
      Certain Chinese populations drinking a large amount of brick tea (>31 per day)
      indicated that individuals of these populations consume more tea than Europeans
      or North Americans result in a comparably higher intake of PCDD/PCDF. Tea
      consumption can attribute to up to 10% of the TDI recommended by WHO (only
      PCDD/PCDF considered, no PCB analyzed).

PMID- 12002473
TI  - Study on PCDDs/PCDFs and co-PCBs content in food samples from Catalonia (Spain).
AB  - The results of a surveillance programme on polychlorinated dibenzo-p-dioxins
      (PCDDs), dibenzofurans (PCDFs) and co-planar polychlorinated biphenyls (co-PCBs)
      determination in 70 foodstuffs samples produced all over the four provinces of
      Catalonia is presented. The study included the analyses of raw milk, pure virgin
      olive oil, butter, chicken. pork and mussel samples collected between November
      1999 and January 2000. Milk, virgin oil, pork or butter presented a variable
      dioxin and co-PCBs content, even though the limits proposed in the draft of the
      EC Regulation for its commercialization in the European countries were not
      reached. The levels of PCDDs/PCDFs and co-PCBs determined in chicken samples
      varied between 0.36-3.59 pg I-TEQ/g fat chicken (0.4--3.8 WHO-TEQ/g fat). Just
      one case presented remarkable content of dioxins (about 30 pg I-TEQ/g fat) with a
      complex congener-specific profile which indicates the presence of an external
      contamination. On the other hand, a congener-specific profile dominated by
      2,3,7,8-TCDF and OCDD was observed in mussel samples from Catalonia. This fact
      was also observed in mussel samples from other sites in Spain.

PMID- 12002474
TI  - Recent survey and effects of cooking processes on levels of PCDDs, PCDFs and Co
      PCBs in leafy vegetables in Japan.
AB  - We report here the latest levels of polychlorinated dibenzo-p
      dioxins/polychlorinated dibenzofurans (PCDD/Fs) and coplanar polychlorinated
      biphenyls (Co-PCBs) in leafy vegetables in Japan as well as the effect of cooking
      processes on the reduction of these contaminants. Three kinds of leafy vegetables
      ("komatsuna", lettuce and spinach) from seven districts in Japan in 1998 were
      analyzed for the 2,3,7,8-chlorine substituted PCDD/Fs and three non-ortho-PCBs
      (#77, 126 and 169). The mean total TEQ levels (using the WHO-TEFs) in the
      komatsuna, lettuce and spinach were 0.094, 0.025 and 0.196 pg/g fresh weight,
      respectively. The TEQ levels are dominated by 2.3,7,8-TCDD, 1,2,3,7,8-PeCDD,
      2,3,4,7,8-PeCDF and 3,3',4,4',5-PeCB in many of the samples. For one of these
      isomers, the 2,4,7,8-PeCDF TEQ levels showed good correlation with the total TEQ
      levels in the samples (r = 0.957). This suggests that 2,3,4,7,8-PeCDF may be an
      indicator for dioxin contamination in the analysis of the leafy vegetables. Also,
      the effects of two cooking processes (washing and washing followed by boiling) on
      the dioxin levels in two types of spinach samples were investigated. On average,
      in both samples, the total concentrations of the PCDDs, PCDFs and Co-PCB were
      reduced to about 38%, 73% and 88% of the initial concentrations by washing. and
      to 21%, 35%, and 61% of the initial concentrations by washing followed by
      boiling. The total TEQ levels were reduced to about 30% of the initial TEQ levels
      by washing followed by boiling. Significant reductions in the TEQ levels were
      observed in the cooked samples. Thus, the cooking processes may reduce the risk
      of dioxin intake from the leafy vegetables.

PMID- 12002475
TI  - Optimization of the ionization conditions for the trace analysis of PCDD/PCDF
      with ion trap MS/MS.
AB  - Commercial ion trap mass spectrometer provides easy-to-operate MS/MS analysis for
      the determination of PCDD/ PCDF. The limit of quantification is appropriately low
      (0.2 pg for 23478-P5CDF) because all the stages are performed in the trap and
      sample losses associated with the ion transportation are minimized. However, if
      excessive ions are injected into the trap, its electrical fields are distorted
      and an overall reduction in performance arises. Ionization condition is an
      important parameter as it affects the amount of the total ions produced. If the
      amount of interfering compounds are negligible, such as standard solution or
      cleaned-up sample, lower ionization condition (e.g. electron energy: 30 eV.
      emission current (EC): 150 microA) is preferable. On the contrary, in case
      excessive interfering ions are coexisting with PCDD/PCDF, such as crude extract
      or semi-cleaned-up sample, the ionization condition should be high (e.g. electron
      energy: 90 eV, EC: 350 microA) for the reproductive quantification.

PMID- 12002476
TI  - Identification of a novel PCB source through analysis of 209 PCB congeners by US
      EPA modified method 1668.
AB  - PCDD/Fs and PCBs in surface waters and effluent waste streams flowing into New
      York/New Jersey Harbor were sampled by large volume filtration and solid phase
      extraction (XAD-2). Passive hexane samplers were employed in sewer trackdown.
      Extraction media were analyzed for 2,3,7,8 substituted PCDD/Fs and all 209 PCB
      congeners. The non-Aroclor PCB congener, 3,3'-DiCB, was ubiquitous in the harbor
      and was found to be associated with pigment manufacture. Knowledge of inadvertent
      synthesis of non-Aroclor PCBs is not new but its magnitude and the generation of
      congeners with dioxin-like properties from this process is novel.

PMID- 12002477
TI  - Detailed study on the levels of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans and polychlorinated biphenyls in Yusho rice oil.
AB  - One bottle of Yusho rice oil was obtained from a Yusho family in 1998. The levels
      of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans
      (PCDFs) and polychlorinated biphenyls (PCBs) in the causal oil were investigated
      with two different approaches and the individual concentrations of all the 17
      2,3,7,8-substituted PCDD/F and 14 coplanar PCB (Co-PCB) congeners were elucidated
      for the first time. The concentrations of PCDDs and PCDFs were found to be 0.60
      and 8.8 ppm, respectively. For PCBs, more than 130 PCB peaks were observed and a
      total concentration of 850 ppm including 170 ppm of Co-PCBs was obtained. The
      toxic equivalents (TEQs) of PCDDs, PCDFs, and Co-PCBs were calculated to be 17,
      470, and 120 ppb, respectively. The relative contribution of these classes to the
      total TEQ in Yusho oil is 3%, 77%, and 20%, respectively, indicating that PCDFs
      play a major role in the toxicity of Yusho oil. Furthermore, it was confirmed
      that 2,3,4,7,8-penta-CDF contributes 58% to the total TEQ, supporting the view
      that this compound is the principal causal agent in Yusho poisoning. It is
      noteworthy that the most toxic 2.3,7,8-tetra-CDD was newly discovered, although
      it contributes only 0.1% to the total TEQ. Based on our data, the smallest TEQ
      intake during the latent period was estimated to be 0.067 mg for Yusho patients.
      This value is about 60% of that previously reported, suggesting a lower minimum
      threshold level for the development of the toxic symptoms of Yusho.

PMID- 12002478
TI  - Development of dioxin toxicity evaluation method in human milk by enzyme-linked
      immunosorbent assay--assay validation for human milk.
AB  - In this study, the development of a toxicity evaluation method for dioxins in
      human milk by enzyme-linked immunosorbent assay (ELISA) was reported. A total of
      17 human milk samples were tested by ELISA and by gas chromatography/mass
      spectrometry (GC/MS) to assess whether the ELISA performed on samples obtained
      from primiparas could be considered as reliable enough for identifying a dioxins
      contamination in human milk. The concept of toxicity equivalent quantity (TEQ)
      screening was validated by comparing TEQ values for a set of human milk samples
      to the ELISA responses predicted for those samples. A fairly good correlation (r
      = 0.920) between immunoassay and GC/MS was achieved for human milk. This ELISA
      should be useful for biological samples monitoring.

PMID- 12002479
TI  - Environmental occurrence of Q1, a C9H3C17N2 compound, that has been identified as
      a natural bioaccumulative organochlorine.
AB  - Environmental appearance of Q1, a natural heptachloro compound with the molecular
      formula C9H3C17N2, was studied in samples from different sites all over the
      world. Q1 was expected to have a bipyrrole backbone, similar to other compounds
      ascribed to natural sources. A method for isolation of Q1 was developed by
      combination of adsorption chromatography on silica and normal phase HPLC with an
      amino phase. UV-detection of Q1 supports the aromatic character of the compound.
      The high levels detected in samples of marine mammals and birds suggested that Q1
      is both a persistent and a bioaccumulative contaminant. This was underscored by
      calculated logK(ow) in the range of other lipophilic organohalogens. In
      accordance with earlier studies, highest Ql concentrations were found in the
      Southern Hemisphere, but with a highly selective GC/ECNI-MS-SIM method, detection
      of Q1 was also achieved in many samples from the Northern Hemisphere. In addition
      to marine mammals and birds. Q1 was also detected in fish from the Mediterranean
      Sea and the Antarctic. Traces were also detected in SRM 1588 certified cod liver
      oil, but Q1 was not detected in fish from Hong Kong and Lake Baikal.

PMID- 12002480
TI  - Triclosan, a commonly used bactericide found in human milk and in the aquatic
      environment in Sweden.
AB  - High levels of the commonly used, effective bactericide Triclosan was found in
      three out of five randomly selected human milk samples. It was also found in the
      bile of fish exposed to municipal wastewater and in wild living fish from the
      receiving waters of the three wastewater treatment plants.

PMID- 12002481
TI  - A cycloheximide-sensitive factor regulates TCDD-induced degradation of the aryl
      hydrocarbon receptor.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototype of environmental
      halogenated aromatic hydrocarbons, induces a rapid reduction in steady state aryl
      hydrocarbon receptor (AhR). Here, we analyzed the biochemical pathway and
      function of the downregulation. Our results reveal that TCDD downregulates the
      AhR protein by shortening the halflife of AhR. The TCDD-induced degradation of
      AhR is inhibited by MG132, a potent inhibitor of the 26S proteasome, indicating
      the ubiquitin-26S proteasome mediated proteolysis as a mechanism for the
      degradation of AhR. Furthermore, inhibition of protein synthesis by cycloheximide
      blocks the degradation of AhR by TCDD, suggesting a labile factor in controlling
      the stability of ligand-activated AhR (hence, designated as AhR degradation
      promoting factor, or ADPF). Analyses of nuclear AhR demonstrated that
      cycloheximide increases nuclear AhR protein and functional AhR/Arnt DNA-binding
      complex, resulting in superinduction of CYP1A1. Lastly, genetic analyses by using
      AhR- or Arnt-defective variant cells demonstrate that superinduction by
      cycloheximide requires the transcription activation (TA) domain of AhR,
      implicating the TA domain in the control of AhR turnover by ADPF. These findings
      provide new insights into the mechanism by which TCDD-activated AhR is regulated
      in nucleus through the 26S proteasome protein degradation pathway.

PMID- 12002482
TI  - A mixture of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs),
      and non-ortho polychlorinated biphenyls (PCBs) changed the lipid content of
      pregnant Long Evans rats.
AB  - Pregnant Long Evans rats received 1.0 microg/kg of dioxin toxic equivalents (TEQ)
      by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that
      contained two polychlorinated dioxins, four polychlorinated furans and three non
      ortho polychlorinated biphenyls (PCBs). Rats were sacrificed on GD 16, GD 21 and
      postnatal day 4 (PND 4). The lipid content of fetus, pup, placenta and maternal
      liver, serum and adipose tissue were determined. Treated GD 16 and GD 21 fetuses
      had identical lipid content to the control group, yet the lipid content of
      treated pups on PND 4 was 32% higher than that of the control group. On the other
      hand, the lipid content of placenta, liver, and serum from the treated dams was
      44-50%, 24%, and 38% lower than that of the control group, respectively. Thus, a
      low-dose mixture of dioxin-like compounds can cause changes in lipid content. The
      lipid content of offspring was not affected until they were exposed via
      lactation.

PMID- 12002483
TI  - Transepithelial transport and cellular accumulation of steroid hormones and
      polychlorobiphenyl in porcine kidney cells expressed with human P-glycoprotein.
AB  - Endocrine disrupters such as sex hormone-like chemicals and the non-physiological
      ligands for aryl hydrocarbon receptor (AhR) exert many adverse biological
      effects. The ligands for AhR disturb gene expression downstream of the gene
      induced by estrogen receptor at a very low concentration. Thus, transepithelial
      transport and cellular accumulation of cortisol (COR) and estrogen as congeners
      of sex hormone-like chemicals, and 3,3',4,4'-tetrachlorobiphenyl (TeCB) as one of
      the ligands for AhR were examined in a monolayer of porcine kidney cells
      transfected with human P-glycoprotein (LLC-COL). The net basal-to-apical
      transport of COR increased in LLC-COL compared to that in the wild type cells
      (LLC-PKI) the same as in vinblastine, whereas the net transport of estradiol
      (EST) was not detected in either cell group. Though the diffusion transports of
      EST for both directions, basal-to-apical and apical-to-basal, were higher than
      that of COR, cellular accumulation of EST was higher than that of COR.
      Transepithelial transport of TeCB was very low and the net basal-to-apical
      transport was not detected, while it was highly accumulated in the epithelial
      cells. The accumulation was slightly higher in LLC-COL than in LLC-PKI at high
      dose.

PMID- 12002484
TI  - The provision of services for spinal disorders.

PMID- 12002485
TI  - Functional imaging and the orthopaedic surgeon.

PMID- 12002486
TI  - Work-related disorders of the upper limb.

PMID- 12002487
TI  - The Exeter universal cemented femoral component at 8 to 12 years. A study of the
      first 325 hips.
AB  - We describe our experience with the implantation of 325 Exeter Universal hips.
      The fate of every implant was known. The procedures were undertaken by surgeons
      of widely differing experience. At follow-up at 12 years, survivorship with
      revision of the femoral component for aseptic loosening as the endpoint was 100%
      (95% CI 98 to 100). Survivorship with revision of the acetabular component for
      aseptic loosening as the endpoint was 96.86% (95% CI 93.1 to 98.9) and that with
      any reoperation as the endpoint 91.74% (95% CI 87.7 to 95.8). No adverse features
      have emerged as a consequence of the modular connection between the head and neck
      of the implant.

PMID- 12002488
TI  - Arthroplasty of the hip. Leg length is not important.
AB  - Discrepancy in leg length after total hip replacement has been associated with
      patient dissatisfaction. We prospectively studied 200 consecutive patients
      undergoing unilateral Charnley hip replacements to identify whether there is a
      demonstrable association between such disparity and postoperative function.
      Radiological measurements between defined points on the pelvis and femur of the
      operated hip were compared with the same points on the contralateral joint. A
      lengthening index was derived and statistical analysis used to compare this with
      validated functional outcome scores (Harris hip score and the SF36 Health Survey)
      and patient satisfaction. Our results showed no statistical association between
      leg-length discrepancy after hip arthroplasty and functional outcome or patient
      satisfaction.

PMID- 12002489
TI  - Quality of life and sports-specific outcomes after Bernese periacetabular
      osteotomy.
AB  - We have undertaken a prospective evaluation of health-related quality-of-life
      outcomes in 26 consecutive patients undergoing periacetabular osteotomy with a
      minimum follow-up of 24 months (24 to 42). The Western Ontario-Macmaster (WOMAC)
      and Short Form 36 (SF-36) outcome measures were evaluated preoperatively and at
      follow-up. Secondary outcome measures included retrospective assessment of sports
      activity and satisfaction with the procedure. Follow-up data were available for
      22 patients (85%). A significant improvement in the pain (p < 0.0001) and
      function (p < 0.0001) scales of the WOMAC and the SF-36 physical score (p <
      0.0001) was seen. The mean sports activity score improved from 1.9 to 4.4, with a
      very high mean satisfaction rating of 89.7/100. A significant improvement in both
      global and disease-specific health outcomes can be expected after this operation,
      with a high rate of satisfaction and improvement in sporting activities.

PMID- 12002490
TI  - A randomised comparison of a foot pump and low-molecular-weight heparin in the
      prevention of deep-vein thrombosis after total knee replacement.
AB  - Patients who undergo total knee replacement (TKR) are at high risk of venous
      thromboembolism. Low-molecular-weight heparins (LMWH) are the most suitable
      chemical prophylactic agents but there are some uncertainties about their safety
      and effectiveness. The foot pump offers an alternative. We randomised 229
      patients undergoing primary, unilateral TKR to receive either the A-V Impulse
      foot pump or enoxaparin, a LMWH. Ascending venography was undertaken between the
      sixth and eighth postoperative day in 188 patients without knowledge of the
      randomisation category. The prevalence of venographic deep-vein thrombosis was
      58% (57/99) in the foot-pump group and 54% (48/89) in the LMWH group which was
      not statistically significant. There were four cases of proximal thrombi and two
      of fatal pulmonary emboli in the foot-pump group and none in the LMWH group.
      There were fewer haemorrhagic complications and soft-tissue effects in the foot
      pump group. We conclude that the neither method provides superior prophylaxis.

PMID- 12002491
TI  - The effect of alignment of the knee on the outcome of unicompartmental knee
      replacement.
AB  - Many authors have recommended undercorrection of the deformity when carrying out
      unicompartmental knee arthroplasty (UKA). The isolated effect of alignment of the
      knee on the outcome of UKA has, however, received little attention. We reviewed
      185 UKAs at a minimum of five years after surgery. They had been carried out by a
      single surgeon using metal-backed tibial components in the management of
      arthritis of the medial compartment. We measured the tibiofemoral angle (TFA)
      before and at four months after operation and at the most recent assessment. The
      amount of correction of the TFA and any subsequent loss were recorded. While
      adjusting for the effects of age, weight and gender of the patients and the type
      and thickness of the implants, the mean correction was significantly less for
      those with a Marmor rating of failure (6.8 degrees) than for those rated
      excellent (9.2 degrees). The mean correction was also significantly less for
      patients with a Marmor rating of failure (6.8 degrees) than for those rated poor
      (11.1 degrees). The mean correction for the UKAs which were revised (6.6 degrees)
      was significantly less than for those not revised (9.1 degrees). Additionally,
      revised UKAs had a significantly higher percentage (63%) of thinner tibial
      implants (<8 mm) than the surviving UKAs (27%). These findings suggest that
      undercorrection of the TFA in UKA of the medial compartment should be avoided,
      particularly if a thin tibial polyethylene insert is used.

PMID- 12002492
TI  - A new generation of artificial ligaments in reconstruction of the anterior
      cruciate ligament. Two-year follow-up of a randomised trial.
AB  - We have undertaken a randomised clinical trial comparing two methods of
      reconstruction of the anterior cruciate ligament in patients with chronic
      instability. We used an ipsilateral bone-patellar-tendon-bone autograft in 27
      patients and the Ligament Advancement Reinforcement System (LARS) artificial
      ligament in 26. Assessment before and at two, six, 12 and 24 months after
      surgery, included the history, physical examination, a modified International
      Knee Documentation Committee (IKDC) score, the Tegner score, the Knee Injury and
      Osteoarthritis Outcome Score (KOOS) and instrumented laxity testing. There were
      no cases of reactive synovitis or of infection of the knee, and there was no
      difference regarding the failure rate between the two groups. The IKDC showed no
      significant differences between the two groups at any stage of the follow-up. The
      KOOS evaluation showed consistently better results in all subscales for the LARS
      group during the first year of follow-up. After 24 months these differences were
      no longer evident. Instrument-tested laxity was greater in the LARS group at all
      stages of follow-up, but the differences were not significant at 24 months. Our
      findings suggest that at follow-up at 24 months the LARS ligament seems to be a
      satisfactory treatment option, especially when an early return to high levels of
      activity is demanded.

PMID- 12002493
TI  - Chronic rupture of tendo Achillis. Long-term results of operative management
      using polyester tape.
AB  - We report the long-term results of the surgical treatment of chronic rupture of
      tendo Achillis using polyester tape. This requires minimal postoperative
      splintage and allows early mobilisation and a prompt return to work and sport. We
      reviewed 16 patients (10 women and 6 men) at a mean period of three years after
      surgery. The median time from injury to operation was 16.8 months (3.9 months to
      13 years), and the median age of the patients was 52 years (27 to 78). The median
      time to full weight-bearing was 40 days and the median time for return to sport
      was 18 weeks (5.4 to 32). One patient required further surgery and one had
      numbness along the distribution of the sural nerve. After surgery only two
      patients had increased dorsiflexion of the ankle compared with the uninjured
      side. There were no cases of rerupture. We recommend this technique for the
      treatment of chronic rupture of tendo Achillis.

PMID- 12002494
TI  - Arthroscopic treatment for osteochondral defects of the talus. Results at follow
      up at 2 to 11 years.
AB  - We reviewed 38 patients who had been treated for an osteochondral defect of the
      talus by arthroscopic curettage and drilling. The indication for surgical
      treatment was persistent symptoms after conservative treatment for at least six
      months. A total of 22 patients had received primary surgical treatment (primary
      group) and 16 had had failed previous surgery (revision group). The mean follow
      up was 4.8 years (2 to 11). Good or excellent results, as assessed by the Ogilvie
      Harris score, were found in 86% in the primary group and in 75% in the revision
      group. Two further procedures were required, one in each group. Radiological
      degenerative changes were seen in one ankle in the revision group after ten
      years. Arthroscopic curettage and drilling are recommended for both primary and
      revision treatment of an osteochondral defect of the talus.

PMID- 12002495
TI  - Fixation of osteochondral lesions of the talus using cortical bone pegs.
AB  - We have treated osteochondral lesions of the talus using cortical bone pegs. We
      examined 27 ankles (27 patients) after a mean follow-up of 7.0 years (2 to 18.8).
      The mean age of the patients was 27.8 years (12 to 62). An unstable osteochondral
      fragment or osteosclerotic changes in the bed of the talus were regarded as
      indications for the procedure. The clinical results were good in 24 ankles (89%)
      and fair in three (11%); none had a poor result. There was also radiological
      improvement in 24 ankles. Repair of the articular surface and stability of the
      lesion can be achieved even in unstable chronic lesions.

PMID- 12002496
TI  - Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome.
      A prospective, randomised, blinded assessment.
AB  - The advantages and disadvantages of endoscopic compared with open carpal tunnel
      release are controversial. We have performed a prospective, randomised, blinded
      assessment in a district general hospital in order to determine if there was any
      demonstrable advantage in undertaking either technique. Twenty-five patients with
      confirmed bilateral idiopathic carpal tunnel syndrome were randomised to undergo
      endoscopic release by the single portal Agee technique to one hand and open
      release to the other. Independent preoperative and postoperative assessment was
      undertaken by a hand therapist who was blinded to the type of treatment. Follow
      up was for 12 months. The operating time was two minutes shorter for the open
      technique (p < 0.005). At all stages of postoperative assessment, the endoscopic
      technique had no significant advantages in terms of return of muscle strength and
      assessment of hand function, grip strength, manual dexterity or sensation. In
      comparison with open release, single-portal endoscopic carpal tunnel release has
      a similar incidence of complications and a similar return of hand function, but
      is a slightly slower technique to undertake.

PMID- 12002497
TI  - Intravenous regional guanethidine blockade in the treatment of post-traumatic
      complex regional pain syndrome type 1 (algodystrophy) of the hand.
AB  - A total of 57 patients, aged between 23 and 86 years, with complex regional pain
      syndrome (CRPS) type 1 nine weeks after an isolated closed fracture of the distal
      radius, was randomised to receive either serial intravenous regional blockade
      (IVRB) with 15 mg of guanethidine in 30 ml of 0.5% prilocaine or serial IVRB with
      30 ml of normal saline at weekly intervals until the tenderness in their fingers
      had resolved or they had received a maximum of four IVRBs. The analgesic efficacy
      was assessed at 24 hours, 48 hours and one week after each procedure by the
      dolorimetry ratio and verbal pain scores, and at intervals up to six months after
      the fracture. There was no significant difference in the number of IVRBs
      administered or in finger tenderness, stiffness or grip strength between the two
      groups. The guanethidine group experienced more pain in the affected hand (p =
      0.025) and at six months had more vasomotor instability (p < 0.0001) compared
      with the control group. IVRB using guanethidine offers no significant analgesic
      advantage over a normal saline placebo block in the treatment of early CRPS type
      1 of the hand after fracture of the distal radius. It does not improve the
      outcome of this condition and may delay the resolution of vasomotor instability
      when compared with the placebo.

PMID- 12002498
TI  - Hydroxyapatite coating improves fixation of pedicle screws. A clinical study.
AB  - We investigated the effects of hydroxyapatite (HA) coating on the purchase of
      pedicle screws. A total of 23 consecutive patients undergoing lumbar fusion was
      randomly assigned to one of three treatment groups. The first received uncoated
      stainless-steel screws, the second screws which were partly coated with HA, and
      the third screws which were fully coated. The insertion torque was recorded.
      After 11 to 16 months, 21 screws had been extracted. The extraction torque was
      recorded. Radiographs were taken to assess fusion and to detect loosening of the
      screws. At removal, the extraction torques exceeded the upper limit of the torque
      wrench (600 Ncm) for many HA-coated screws. The calculated mean extraction torque
      was 29 +/- 36 Ncm for the uncoated group, 447 +/- 114 Ncm for the partly-coated
      group and 574 +/- 52 Ncm for the fully-coated group. There were significant
      differences between all three groups (p < 0.001). There were more radiolucent
      zones surrounding the uncoated screws than the HA-coated screws (p < 0.001). HA
      coating of pedicle screws resulted in improved fixation with reduced risk of
      loosening of the screws.

PMID- 12002499
TI  - Indications of disordered eating behaviour in adolescent patients with idiopathic
      scoliosis.
AB  - We have investigated whether patients with adolescent-onset idiopathic scoliosis
      (AIS) are more likely to have a low body-weight. Measurements of weight, height
      and body mass index (BMI) were made in 44 young women with AIS and compared with
      age- and gender-adjusted normative data. The body mass criteria of the
      International Classification of Diseases for eating disorders was used to
      determine how many patients were within the range considered to be 'eating
      disordered'. Compared with the normative data, the AIS group did not differ
      significantly in terms of height, (p = 0.646), but they were significantly
      lighter (p < 0.001) and had significantly lower BMI scores (p < 0.001); 25% of
      the series had BMI scores which were within the range considered to be anorexic.
      The relationship between a diagnosis of AIS and low body-weight may indicate
      disordered eating and is thus a cause for concern, particularly in the light of
      the well-established relationship between eating psychopathology and
      osteoporosis. Aspects of organic health may need to be considered in addition to
      the cosmetic deformity.

PMID- 12002500
TI  - Surgical outcomes in osteosarcoma.
AB  - From the European Osteosarcoma Intergroup study 202 patients were assessed with
      respect to their surgical treatment. Although treated in three different centres
      the survival of the three groups was identical (57% at five years). Two of the
      centres had rates of limb salvage of 85% and 83%, respectively, while the third
      had a rate of 49%. The corresponding risks of local recurrence were 13.3%, 6.8%
      and 2.5%, with all local recurrences arising in limbs with attempted limb
      salvage. Local recurrence was closely related to the adequacy of the margins of
      excision and to the chemotherapeutic response. Patients who had undergone limb
      salvage surgery and who developed local recurrence still had a better survival
      than those who had primary amputation (37% v 31% survival at five years). Of
      patients who relapsed, 31% of those with local recurrence alone were cured by
      further treatment, as compared with only 10% of those with metastases. Limb
      salvage surgery with effective chemotherapy remains the optimum treatment for
      osteosarcoma.

PMID- 12002501
TI  - Revision of the Kotz type of tumour endoprosthesis for the lower limb.
AB  - In 251 patients over a period of 15 years an uncemented Kotz modular femoral and
      tibial reconstruction mega prosthesis was implanted after resection of a
      malignant tumour of the lower limb. Twenty-one patients (8.4%) underwent revision
      for aseptic loosening, again using an uncemented prosthesis, and five of these
      required a further revision procedure. The median follow-up time from the first
      revision was 60 months (11 to 168) and after a second revision, 33 months (2 to
      50). The probability of a patient avoiding aseptic loosening for ten years was
      96% for a proximal femoral, 76% for a distal femoral and 85% for a proximal
      tibial implant. At the time of follow-up all radiographs were assessed according
      to the International Symposium of Limb Salvage criteria. The first radiological
      signs of aseptic loosening were always seen at the most proximal or distal part
      of the anchorage stem at a mean of 12 months (4 to 23) after the first
      implantation. Using the Musculoskeletal Tumor Society score for evaluation, the
      clinical results showed a mean of 88% of normal function.

PMID- 12002502
TI  - Unicameral bone cysts treated by injection of bone marrow or methylprednisolone.
AB  - In 79 consecutive patients with unicameral bone cysts we compared the results of
      aspiration and injection of bone marrow with those of aspiration and injection of
      steroid. All were treated by the same protocol. The only difference was the
      substance injected into the cysts. The mean radiological follow-up to detect
      activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a
      total of 27 injections of bone marrow and 65 a total of 99 injections of steroid.
      Repeated injections were required in 57% of patients after bone marrow had been
      used and in 49% after steroid. No complications were noted in either group. In
      this series no advantage could be shown for the use of autogenous injection of
      bone marrow compared with injection of steroid in the management of unicameral
      bone cysts.

PMID- 12002503
TI  - Management of completely displaced metaphyseal fractures of the distal radius in
      children. A prospective, randomised controlled trial.
AB  - In a prospective, randomised controlled trial, 68 children who had a completely
      displaced metaphyseal fracture of the distal radius were treated either by
      manipulation (MUA) and application of an above-elbow cast alone or by the
      additional insertion of a percutaneous Kirschner (K-) wire. Full radiological
      follow-up to union was obtained in 65 children and 56 returned for clinical
      evaluation three months after injury. Maintenance of reduction was significantly
      better in the K-wire group and fewer follow-up radiographs were required. There
      was no significant difference in the clinical outcome measured three months after
      injury. Seven of 33 patients in the MUA group had to undergo a second procedure
      because of an unacceptable position compared with none of the 35 in the K-wire
      group (chi-squared test, p < 0.01). One patient in the K-wire group required
      exploration for recovery of a migrated wire. We conclude that the use of a
      percutaneous K-wire to augment the reduction of the fracture in children who have
      a completely displaced metaphyseal fracture of the distal radius is a safe and
      reliable way of maintaining alignment of the fracture.

PMID- 12002504
TI  - The natural history of developmental dysplasia of the hip after early supervised
      treatment in the Pavlik harness. A prospective, longitudinal follow-up.
AB  - Between June 1988 and December 1997, we treated 332 babies with 546 dysplastic
      hips in a Pavlik harness for primary developmental dysplasia of the hip as
      detected by the selective screening programme in Southampton. Each was managed by
      a strict protocol including ultrasonic monitoring of treatment in the harness.
      The group was prospectively studied during a mean period of 6.5 +/- 2.7 years
      with follow-up of 89.9%. The acetabular index (AI) and centre-edge angle of
      Wiberg (CEA) were measured on annual radiographs to determine the development of
      the hip after treatment and were compared with published normal values. The
      harness failed to reduce 18 hips in 16 patients (15.2% of dislocations, 3.3% of
      DDH). These required surgical treatment. The development of those hips which were
      successfully treated in the harness showed no significant difference from the
      normal values of the AI for the left hips of girls after 18 months of age. Of
      those dysplastic hips which were successfully reduced in the harness, 2.4% showed
      persistent significant late dysplasia (CEA <20 degrees) and 0.2% persistent
      severe late dysplasia (CEA <15 degrees). All could be identified by an abnormal
      CEA (<20 degrees) at five years of age, and many from the progression of the AI
      by 18 months. Dysplasia was considered to be sufficient to require innominate
      osteotomy in five (0.9%). Avascular necrosis was noted in 1% of hips treated in
      the harness. We conclude that, using our protocol, successful initial treatment
      of DDH with the Pavlik harness appears to restore the natural development of the
      hip to normal. We suggest that regular radiological surveillance up to five years
      of age is a safe and effective practice.

PMID- 12002505
TI  - Avascular necrosis after osteotomy of the talar neck to correct residual club
      foot deformity in children. A long-term review.
AB  - In order to determine the incidence of avascular necrosis after osteotomy of the
      talar neck, we re-evaluated 11 patients (16 feet) with idiopathic club foot who
      had undergone this procedure at a mean age of eight years (5 to 13) to correct a
      residual adduction deformity. All had been initially treated conservatively and
      operatively. The mean follow-up was 39 years (36 to 41). Surgery consisted of a
      closing-wedge osteotomy of the talar neck combined, in 14 feet, with lengthening
      of the first cuneiform and a Steindler procedure. At follow-up eight feet were
      free from pain, three had occasional mild pain and five were regularly painful
      after routine activities. Two patients were unlimited in their activity, six
      occasionally limited after strenuous and three regularly limited after strenuous
      activity. Using the Ponseti score, the feet were rated as good in four, fair in
      three and poor in nine. In seven feet avascular necrosis with collapse and
      flattening of the talar dome had occurred. In all of these feet the children were
      younger than ten years of age at the time of surgery. In three feet, avascular
      necrosis of the talar head was also observed. We conclude that osteotomy of the
      talar neck in children under the age of ten years can cause avascular necrosis
      and should be abandoned.

PMID- 12002506
TI  - Calcifying tendonitis of the gastrocnemius. A report of three cases.
AB  - We describe the clinical features of calcifying tendonitis in the medial head of
      gastrocnemius in three elderly female patients. The presenting symptom was
      chronic pain in the posteromedial area of the knee in two patients and acute pain
      in the back of the knee in one. All had limitation of movement of the knee and
      marked tenderness in the region of the tendinous origin of the medial head of
      gastrocnemius with posterior knee pain induced by stretching the tendon. An
      injection of 1% lidocaine and steroid into the tendon resulted in temporary
      relief from pain and improved movement.

PMID- 12002507
TI  - Circulating levels of insulin-like growth factor-1 and insulin-like growth factor
      binding protein-3 in patients with severe head injury.
AB  - There is evidence to suggest that fractures heal more rapidly in patients with a
      head injury as a result of systemic factors released from the site of this
      injury. We have measured the circulating level of insulin-like growth factor-1
      (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known
      involvement in the stimulation of the activity of osteoblasts and the healing of
      fractures. The serum level of IGF-1 was significantly lower in patients with both
      head injury and fracture and fracture only compared with that in healthy
      volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also
      significantly lower in patients with both head injury and fracture (p < 0.01).
      Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from
      week to week in both the patients and healthy control subjects. These results
      indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be
      responsible for the altered healing of fractures seen in conjunction with head
      injury.

PMID- 12002508
TI  - The effect of increased stress on the patellar tendon.
AB  - We performed a biomechanical and histological study to clarify the effect of
      stress enhancement on the in situ frozen-thawed patellar tendon of the rabbit as
      a tendon autograft model. We used 48 Japanese White rabbits divided into three
      groups. In group 1, the patellar tendon underwent in situ freeze-thaw treatment
      with liquid nitrogen to kill intrinsic fibroblasts. In group 2, after similar
      treatment, the medial and lateral portions were resected so that the cross
      sectional area was reduced by a third. In group 3, after treatment, the cross
      sectional area was reduced by a half. In groups 2 and 3, the stress in the tendon
      was calculated theoretically to be 150% and 200% of the physiological stress
      during locomotion. Eight rabbits in each group were killed at three and six
      weeks, respectively. At three weeks, the mean values for the tensile strength of
      groups 2 and 3 were 113.7% and 75.7% of that of group 1, and at six weeks 101.2%
      and 57.4%, respectively. The tensile strength in group 3 was significantly lower
      than that in groups 1 and 2. The histological findings in group 2 were similar to
      those in group 1, although an acellular area appeared to be wider in the core
      portion compared with group 1 at each period. In group 3, the collagen bundles of
      the tendon were less organised than those of groups 1 and 2. Our findings showed
      that stress enhancement affects the remodelling of the frozen-thawed patellar
      tendon and that excessively high stress reduces the mechanical properties of the
      tendon. This indicates that high stress on the patellar tendon autograft should
      be avoided during ligament reconstruction.

PMID- 12002509
TI  - Comparison of polyethylene wear with femoral heads of 22 mm and 32 mm. A
      prospective, randomised study.
AB  - In this prospective, randomised study, we have compared the wear rate of
      cemented, acetabular polyethylene cups articulating with either a 22 mm or a 32
      mm cobalt-chromium head. We evaluated 89 patients who had a total of 484
      radiographs. The mean follow-up period was 71.4 months (SD 29.1). All the
      radiographs were digitised and electronically measured. The linear wear rate was
      significantly higher during the first two years and decreased after this period
      to a constant value. We suggest that this is partly due to a 'run-in' process
      caused by irregularities between surfaces of the cup and head and an initial
      plastic deformation of the polyethylene. The mean volumetric wear was 120.3
      mm/year for the 32 mm head, which was significantly higher than the 41.5 mm3/year
      for the 22 mm heads. The mean linear wear rate was not significantly different.
      We were, however, unable to find radiological signs of osteolysis in the patients
      who had higher wear rates.

PMID- 12002510
TI  - Human mesenchymal tumour-associated macrophages differentiate into osteoclastic
      bone-resorbing cells.
AB  - The cellular mechanisms which account for the formation of osteoclasts and bone
      resorption associated with enlarging benign and malignant mesenchymal tumours of
      bone are uncertain. Osteoclasts are marrow-derived, multinucleated, bone
      resorbing cells which express a macrophage phenotype. We have determined whether
      tumour-associated macrophages (TAMs) isolated from benign and malignant
      mesenchymal tumours are capable of differentiating into osteoclasts. Macrophages
      were cultured on both coverslips and dentine slices for up to 21 days with UMR
      106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)
      and human macrophage colony-stimulating factor (M-CSF) or, in the absence of UMR
      106 cells, with M-CSF and RANK ligand. In all tumours, the formation of
      osteoclasts from CD14-positive macrophages was shown by the formation of tartrate
      resistant-acid-phosphatase and vitronectin-receptor-positive multinucleated cells
      which were capable of carrying out lacunar resorption. These results indicate
      that the tumour osteolysis associated with the growth of mesenchymal tumours in
      bone is likely to be due in part to the differentiation of mononuclear phagocyte
      osteoclast precursors which are present in the TAM population of these lesions.

PMID- 12002511
TI  - Extracorporeal shock wave promotes growth and differentiation of bone-marrow
      stromal cells towards osteoprogenitors associated with induction of TGF-beta1.
AB  - Extracorporeal shock-wave (ESW) treatment has been shown to be effective in
      promoting the healing of fractures. We aimed to determine whether ESW could
      enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the
      left femur of rats 10 mm above the knee at 0.16 mJ/mm2 in a range of between 250
      and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and
      subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes,
      erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU
      osteoprogenitors (CFU-O). We found that the mean value for the CFU-O colonies
      after treatment with 500 impulses of ESW was 168.2 CFU-O/well (SEM 11.3) compared
      with 88.2 CFU-O/well (SEM 7.2) in the control group. By contrast, ESW treatment
      did not affect haematopoiesis as shown by the CFU-Mix (p = 0.557). Treatment with
      250 and 500 impulses promoted CFU-O, but not CFU-Mix formations whereas treatment
      with more than 750 impulses had an inhibiting effect. Treatment with 500 impulses
      also enhanced the activity of bone alkaline phosphatase in the subculture of CFU
      O (p<0.01), indicating a selective promotion of growth of osteoprogenitor cells.
      Similarly, formation of bone nodules in the long-term culture of bone-marrow
      osteoprogenitor cells was also significantly enhanced by ESW treatment with 500
      impulses. The mean production of TGF-beta1 was 610 pg/ml (SEM 84.6) in culture
      supernatants from ESW-treated rats compared with 283 pg/ml (SEM 36.8) in the
      control group. Our findings suggest that optimal treatment with ESW could enhance
      rat bone-marrow stromal growth and differentiation towards osteoprogenitors
      presumably by induction of TGF-beta1.

PMID- 12002512
TI  - The radial and posterior interosseous nerves.

PMID- 12002513
TI  - The inferior capsular shift operation for instability of the shoulder: long-term
      results in 34 shoulders.

PMID- 12002514
TI  - Treatment for displaced intracapsular fracture of the proximal femur.

PMID- 12002515
TI  - A comparison of polyethylene wear in hips with cobalt-chrome or zirconia heads.

PMID- 12002516
TI  - Current concepts of respiratory insufficiency syndromes after fracture.

PMID- 12002517
TI  - Characterisation of the non-peptide nociceptin receptor agonist, Ro64-6198 in
      Chinese hamster ovary cells expressing recombinant human nociceptin receptors.
AB  - Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid receptor
      like receptor or nociceptin receptor (NOP). We have compared a novel non-peptide
      NOP agonist Ro64-6198 with N/OFQ in a series of GTPgamma35S binding and
      inhibition of forskolin stimulated cAMP formation assays. GTPgamma35S binding
      assays were performed in membranes prepared from Chinese hamster ovary cells
      expressing the recombinant human NOP (CHOhNOP). cAMP inhibition studies were
      performed in whole CHOhNOP cells. Both Ro64-6198 and N/OFQ stimulated GTPgamma35S
      binding with pEC50 values(95%CL) of 7.61(0.18) and 8.58(0.21) respectively. Both
      Ro64-6198 and N/OFQ inhibited cAMP formation with pEC50 values of 8.45(0.9) and
      9.28(028) respectively. In each assay Ro64-6198 and N/OFQ were full agonists.
      Ro64-6198 stimulation of GTPgamma35S binding and inhibition of cAMP formation was
      competitively antagonised by the NOP antagonists [Nphe1]NC(1 - 13)NH2 (10microM),
      J-113397 (100nM) and III-BTD (1microM) with pKB values of 7.04(0.34) and
      6.29(0.10), 8.65(0.34) and 7.90(0.30) and 7.59(0.22) and 7.60(0.22) respectively.
      Despite the slightly reduced potency of Ro64-6198 compared with N/OFQ, by virtue
      of high selectivity and relative metabolic stability this molecule will be of
      considerable use in studies of the actions of the NOP.

PMID- 12002518
TI  - Role of benzodiazepine-GABAA receptor complex in attenuation of U-50,488H-induced
      analgesia and inhibition of tolerance to its analgesia by ginseng total saponin
      in mice.
AB  - In the present study, the role of benzodiazepine-GABAA receptor complex in the
      attenuation of U-50,488H (U50), a selective kappa opioid agonist-induced
      analgesia and inhibition of tolerance to its analgesia by ginseng total saponin
      (GTS) was investigated using the mice tail-flick test. The intraperitoneal (i.p.)
      treatment of GTS (100 and 200 mg/kg) and diazepam (0.1-1 mg/kg) dose-dependently
      attenuated the U50 (40 mg/kg, i.p.)-induced analgesia. GTS (0.001-10 microg/ml)
      did not alter binding of [3H]naloxone to mice whole brain membrane. The
      attenuation effect of GTS (100 mg/ kg) and diazepam (0.5 mg/kg) on U50-induced
      analgesia was blocked by flumazenil (0.1 mg/kg, i.p.), a benzodiazepine receptor
      antagonist, and picrotoxin (1 mg/kg, i.p.), a GABAA-gated chloride channel
      blocker. However, bicuculline (1 mg/kg, i.p.), a GABAA receptor antagonist
      blocked the attenuation effect of diazepam (0.5 mg/kg) but not GTS (100 mg/kg) on
      U50-induced analgesia. Chronic treatment (day 4-day 6) of GTS (50-200 mg/kg) and
      diazepam (0.1-1 mg/kg) dose-dependently inhibited the tolerance to U50-induced
      analgesia. Flumazenil (0.1 mg/kg) and picrotoxin (1 mg/kg) on chronic treatment
      blocked the inhibitory effect of GTS (100 mg/kg) and diazepam (0.5 mg/kg) on
      tolerance to U50-induced analgesia. On the other hand, chronic treatment of
      bicuculline (1 mg/kg) blocked the inhibitory effect of diazepam (0.5 mg/kg) but
      not GTS (100 mg/kg) on tolerance to U50-induced analgesia. In conclusion, the
      findings suggest that GTS attenuates U50-induced analgesia and inhibits tolerance
      to its analgesia and this action involves benzodiazepine receptors and GABAA
      gated chloride channels.

PMID- 12002519
TI  - Sleep deprivation in depression stabilizing antidepressant effects by repetitive
      transcranial magnetic stimulation.
AB  - Partial sleep deprivation (PSD) has a profound and rapid effect on depressed
      mood. However, the transient antidepressant effect of PSD - most patients relapse
      after one night of recovery sleep - is limiting the clinical use of this method.
      Using a controlled, balanced parallel design we studied, whether repetitive
      transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able
      to prevent this relapse. 20 PSD responders were randomly assigned to receive
      either active or sham stimulation during the following 4 days after PSD. Active
      stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD
      up to 4 days. This finding indicates that rTMS is an efficacious method to
      prevent relapse after PSD.

PMID- 12002520
TI  - Validation of a behavioral recording automated system in the elevated plus-maze
      test.
AB  - The elevated plus-maze test has been widely used for screening of anxiolytic
      drugs and for exploring neurobiological bases of anxiety. In this study, we
      validated a new automated system that enables to record exploratory behavior in
      the elevated plus-maze test. This system, called cyberplus, consisted of ten
      pairs of photoelectric cells strategically located in several parts of the
      apparatus, and seemed to be sensitive to the position of the animal's forepaws,
      so it would yield scores in anxiety measurements and locomotor activity similar
      to those obtained by following the traditional procedure, that is, by analyzing
      videotapes by experienced observers. In order to assess this hypothesis, we
      exposed rats to the elevated plus-maze test and compared the scores obtained by
      cyberplus with the values recorded by two independent observers, conducting a
      correlational study with both kinds of recording procedures. The results obtained
      suggest the utility of cyberplus as a behavioral recording automated system in
      the elevated plus-maze test, making data collection and data analysis easier in
      exploring pharmacological and neurobiological bases of anxiety.

PMID- 12002521
TI  - Geldanamycin inhibits trichostatin A-induced cell death and histone H4
      hyperacetylation in COS-7 cells.
AB  - As widely believed treating cells with trichostatin A (TSA), an inhibitor of
      histone deacetylase, results in histone H4 hyperacetylation and cell cycle
      arrest. This compound is often compared with other potential anticancer drugs in
      cell cycle, proliferation and differentiation research. Furthermore, geldanamycin
      (GA), a 90-kDa heat shock protein (HSP90) specific inhibitor, is a well-known
      potential anticancer agent. This study examines whether GA can affect the
      cellular functions induced by TSA. When using TSA treatment, although caused COS
      7 cell death, pretreatment of 0.5 microg/ml GA for 30 min and an addition of 50
      ng/ml TSA (GA + TSA) apparently averted cell death. Our results indicated that
      the cell survival rate was only approximately 20% when prolonged treatment was
      undertaken with 50 ng/ml TSA (TSA) alone for 24 h. In contrast, the cell survival
      rate was enhanced by two folds when treating with GA + TSA. Furthermore, DNA
      fragmentation assay revealed that fragmented DNA was produced 8 h after prolonged
      treatment with TSA alone. Within 16 h, the apoptotic percentages of TSA-treated
      cells were between 15-25%. In contrast, the other treatments did not exceed 6%.
      Furthermore, GA inhibited TSA-induced histone H4 hyperacetylation. Western
      blotting analysis further demonstrated that the HSP70 levels did not
      significantly increase in TSA-treated cells. However, the accumulated 70-kDa heat
      shock protein (HSP70) markedly increased up to 2 to 3 folds at 8 h in GA- and GA
      + TSA-treated cells, and the maximum amount up to 5 to 7 folds at 20 h.
      Conversely, HSP90 did not markedly increase in all treatments. Based on the
      results in this study, we suggest that apoptosis induced by TSA can be prevented
      by GA-induced increment of heat shock proteins, particularly HSP70.

PMID- 12002522
TI  - 1,25-dihydroxyvitamin D3 receptor is upregulated in aortic smooth muscle cells
      during hypervitaminosis D.
AB  - Several studies have demonstrated that excess of vitamin D3 is toxic particularly
      to vascular tissues. A notable pathological feature is arterial calcification.
      The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of
      arterial calcification are not clearly understood. The present study was
      undertaken to explore whether arterial calcification is a sequel of increased
      calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D
      receptor in the cells in response to elevated circulating levels of vitamin D3 in
      serum. The experimental study was performed in 20 New Zealand white female
      rabbits aged 6 months. Animals in the test group were injected 10,000 IU of
      cholecalciferol intramuscularly twice a week for one month. Six control animals
      were given intra-muscular injections of plain cottonseed oil. Animals were
      sacrificed and aortas were examined for pathological lesions, 1,25
      dihyroxyvitamin D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth
      muscle cells. Serum samples collected at intervals were assayed for levels of 25
      OH-D3 and calcium. The results showed that in animals given injections of
      cholecalciferol, serum levels of 25-OH-D3 were elevated. In four of these animals
      calcification and aneurysmal changes were seen in the aorta. Histological lesions
      comprised of fragmentation of elastic fibers as well as extensive loss of elastic
      layers. 1,25(OH)2 D3 receptor levels were up regulated and 45Ca uptake enhanced
      in aortas of animals which were given excessive vitamin D3. The evidences
      gathered suggest that excess vitamin D is arteriotoxic and that the vitamin
      induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and
      increased calcium uptake in smooth muscle cells of the arteries.

PMID- 12002523
TI  - Effects of thermal denaturation on protein glycation.
AB  - Protein denaturation occurs at sites of inflammation. We hypothesized that
      denatured protein may provide a more susceptible target for glycation, which is a
      known mediator of inflammation. We examined the effects of thermal denaturation
      on the susceptibility of protein glycation using glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) and aspartate aminotransferase (AAT) as our target
      proteins. GAPDH and AAT are ubiquitous proteins that exhibited very different
      thermal stabilities. Glycating agents, methylglyoxal (MG) and glyceraldehyde
      (Glyc), caused an increase in the formation of advanced glycation endproducts
      (AGEs) in native and denatured GAPDH and AAT. The effects of the glycating agents
      were more pronounced with the denatured proteins. In addition to nitroblue
      tetrazolium (NBT)- reactivity, our measured endpoints were absorbance (lambda =
      365 nm) and fluorescence (lambda(ex) = 370 nm; lambda(em) = 470 nm) properties
      that are typically associated with protein glycation. We also looked at
      carnosine's ability to prevent glycation of native and denatured protein.
      Carnosine, an endogenous histidine dipeptide, exhibits anti-inflammatory activity
      presumably due to its anti-oxidant and anti-glycation properties. Carnosine
      prevented Glyc-induced AGE formation in both native and denatured AAT suggesting
      that carnosine's anti-inflammatory activity may be due in part to carnosine's
      ability to prevent glycation of denatured protein.

PMID- 12002524
TI  - Forskolin fails to activate L-type calcium current in hypertrophied
      cardiomyocytes of chronically hypoxic rats.
AB  - We have shown that the contractile, cytosolic calcium ([Ca2+]i) and cyclic AMP
      (cAMP) responses to beta-adrenoceptor stimulation are attenuated in ventricular
      myocytes of chronically hypoxic (CH) rats. The aim of this study was to examine
      the effect of forskolin on the L-type Ca2+ current in CH hypertrophied
      ventricular myocytes. Patch-clamp recording of the L-type Ca2+ current was
      measured in right ventricular myocytes of normoxic control and CH rats exposed to
      10% inspired oxygen for 4 weeks. The breadth, but not the length, of CH myocytes
      was significantly greater than that of the control group. Activation of beta
      adrenoceptor with isoproterenol (0.1 microM) increased the peak Ca2+ current by
      83% in the normoxic control but the increase of peak Ca2+ current was not
      significant in the CH myocytes. Forskolin (0.1 - 1 microM), an activator of
      adenylyl cyclase, increased the peak Ca2+ current by 49% - 102% in the normoxic
      controls but it did not cause significant change of the peak Ca2+ current in CH
      myocytes. These results suggest an absence of forskolin-induced activation of
      Ca2+ current in hypertrophied ventricular myocytes during chronic hypoxia. The
      failure of activation of the Ca2+ current is consistent with the idea that
      adenylyl cyclase function is down-regulated in CH hypertrophied myocytes.

PMID- 12002525
TI  - Combined effect of ACE inhibitor and exercise training on insulin resistance in
      type 2 diabetic rats.
AB  - The aim of this study was to investigate whether a combined treatment of ACE
      inhibitor and exercise training is more effective than either treatment alone in
      alleviating the insulin resistant states in the Otsuka Long-Evans Tokushima Fatty
      (OLETF) rat, a model of type 2 diabetes. OLETF rats (25 weeks old) were randomly
      divided into 5 groups; sedentary control, exercise-trained, temocapril (ACE
      inhibitor; 2 mg/kg/day)-treated, with and without exercise, and losartan (AT1
      receptor antagonist; 1 mg/kg/day)-treated. Long-Evans Tokushima Otsuka rats were
      used as a non-diabetic control. Body weight, the amount of abdominal fat and
      blood pressure were higher for OLETF rats than for control rats. However, glucose
      infusion rate (GIR), an index of insulin resistance, was decreased greatly in
      OLETF rats. The fasting levels of blood glucose, insulin and lipids were also
      increased in the diabetic strain. In OLETF rats, both temocapril and losartan
      reversed hypertensive states significantly, whereas GIR and hyperlipidemia were
      improved when rats were treated with ACE inhibitors, but not with the AT1
      receptor antagonist. Exercise training decreased body weight and the amount of
      abdominal fat, and also increased GIR in parallel with improved dislipidemia. The
      combination of the ACE inhibitor with exercise training also improved obesity,
      hyperinsulinemia, dislipidemia and fasting level of blood glucose, and this
      combination resulted in the greatest improvement of insulin resistance. These
      results suggest that the combination of ACE inhibitor and exercise training may
      be a beneficial treatment for mixed diabetic and hypertensive conditions.

PMID- 12002527
TI  - Public health implications of campylobacter outbreaks in England and Wales, 1995
      9: epidemiological and microbiological investigations.
AB  - Although campylobacter has been the most commonly recognized bacterial cause of
      gastrointestinal infection in England and Wales since 1981, there are few
      reported campylobacter outbreaks. Of the 2374 general outbreaks of infectious
      intestinal disease reported to CDSC between 1995 and 1999, for which an
      aetiological agent was identified, campylobacter accounted for only 50 (2%).
      Foodborne transmission was identified in 35 outbreaks and the majority took place
      in commercial catering establishments; waterborne transmission was responsible
      for a further four outbreaks. Isolates of Campylobacter jejuni were referred for
      typing from 25 outbreaks. In 13 outbreaks all isolates were the same subtype, as
      defined by serotype and phage type, while in the remainder more than one
      campylobacter subtype was involved.

PMID- 12002526
TI  - Interactive gene expression pattern in prostate cancer cells exposed to phenolic
      antioxidants.
AB  - Dietary phenolic compounds are known to elicite vital cellular responses such as
      cell cycle arrest, apoptosis and differentiation by activating a cascade of
      molecular events. As there is an increasing interest to improve the efficacy of
      these compounds for use as potential chemopreventive agents, we wanted to
      understand the impact of phenolic compounds on target genes in prostate cancer.
      In this study we used human cDNA microarrays with 2400 clones consisting of 17
      prosite motifs to characterize alterations in gene expression pattern in response
      to the phenolic antioxidants ellagic acid (EA) and resveratrol (RE). Over a 48-hr
      exposure of androgen - sensitive LNCaP cells to EA and RE, a total of 593 and 555
      genes respectively, showed more than a two fold difference in expression. A
      distinct set of genes in both EA-and RE-treated cells may represent the signature
      profile of phenolic antioxidant-induced gene expression in LNCaP cells. Although
      extensive similarity was found between effects of EA - and RE - responsive genes
      in prostate cancer cells, out of 246 genes with overlapping responses, 25 genes
      showed an opposite effect. Quantitative RT-PCR was used to verify and validate
      the differential expression of selected genes identified from cDNA microarrays.
      In-depth analysis of the data from this study provided insight into the
      alterations in the p53 - responsive genes, p300, Apaf-1, NF-kBp50 and p65 and
      PPAR families of genes, suggesting the activation of multiple signaling pathways
      that leads to growth inhibition of LNCaP cells. This is a first study to look for
      changes in a large number of human genes in response to dietary compounds.

PMID- 12002528
TI  - Phage typing and PFGE pattern analysis as tools for epidemiological surveillance
      of Salmonella enterica serovar Bovismorbificans infections.
AB  - Some years ago, an increase in the number of sporadic cases and outbreaks of
      salmonellosis due to S. enterica serovar Bovismorbificans was observed in several
      European countries including Finland, Sweden, England/Wales, Austria, and
      Germany. In order to understand the recent spread of this serovar and to trace
      the route of infection back to its source, it was considered necessary to subtype
      S. Bovismorbificans isolates. Using phage typing (newly described here) and
      molecular fingerprinting (PFGE-pattern, plasmid profiles and ribotype) the
      isolates of European origin could be subtyped and compared to S. Bovismorbificans
      isolates that originated in overseas countries such as Australia, Thailand,
      India, etc. where this serovar was isolated more frequently. Significant clonal
      diversity was identified but some of the clonal types of S. Bovismorbificans
      dominated the epidemics and single cases in Europe as well as in overseas
      countries. The clonal identity among these isolates indicates an international
      distribution, new sources of infection, and highlights the urgent requirement for
      standardized laboratory based surveillance networks (e.g. Enter-Net). Moreover,
      it is suggested that strains of S. Bovismorbificans will continue to be of
      concern in public health and that phage typing together with PFGE typing can be
      applied as reliable and rapid tools for their future monitoring.

PMID- 12002529
TI  - Incidence and molecular analysis of Vibrio cholerae associated with cholera
      outbreak subsequent to the super cyclone in Orissa, India.
AB  - An epidemiological study was carried out to find out the aetiological agent for
      diarrhoeal disorders in the cyclone and flood affected areas of Orissa, India.
      Rectal swabs collected from 107 hospitalized diarrhoea patients were
      bacteriologically analysed to isolate and identify the various enteropathogens.
      Detection of toxic genes among E. coli and V. cholerae was carried out by
      polymerase chain reaction (PCR) assay. Of the 107 rectal swabs analysed, 72.3%
      were positive for V. cholerae O1 Ogawa, 7.2% for V. cholerae O139, 1.2% for E.
      coli (EAggEC) and 1.2% for Shigella flexneri type 6. Using multiplex PCR assay it
      was found that all V. cholerae isolates were ctxA positive and El Tor biotype.
      Strains of V. cholerae O1 were observed to be resistant to nalidixic acid,
      furazolidone, streptomycin, co-trimoxazole and ampicillin. Except for nalidixic
      acid, the resistance pattern for O139 was identical to that of O1 strains.
      Representative strains of V. cholerae were further characterized by randomly
      amplified polymorphic DNA (RAPD) analysis and ribotyping. Both O1 and O139 V.
      cholerae strains exhibited the R3 pattern of ribotype and belonged to a similar
      pattern of RAPD compared with that of Calcutta strains. Early bacteriological and
      epidemiological investigations have revealed the dominance of V. cholerae O1
      among the hospitalized patients in cyclone affected areas of Orissa. Drinking
      water scarcity and poor sanitation were thought to be responsible for these
      diarrhoeal outbreaks. Timely reporting and implementation of appropriate control
      measures could contain a vital epidemic in this area.

PMID- 12002530
TI  - Incidence of invasive pneumococcal disease in Scotland, 1988-99.
AB  - A review of the epidemiology of invasive pneumococcal disease in Scotland was
      carried out using data from laboratory-based systems during the period 1988-99.
      This comprised 5456 (90.8%) isolates of Streptococcus pneumoniae from blood, 467
      (7.8%) from cerebrospinal fluid (CSF) and 84 (1.4%) from other sterile sites. The
      mean annual incidence of invasive disease was 9.8/10(5) population (9.0/10(5) for
      bacteraemia and 0.8/10(5) for meningitis). Invasive disease was highest in
      children < 2 years of age and in the elderly > or = 65 years (44.9/10(5) and
      28.4/10(5) population in these age groups respectively). The highest incidence of
      pneumococcal meningitis, 11.8/10(5) persons occurred in children < 2 years of
      age. Males had a higher incidence of pneumococcal bacteraemia and meningitis than
      females (male:female = 1.2:1 for bacteraemia (RR = 1.17, 95 % CI 1.11, 1.24) and
      1.5:1 for meningitis (RR = 1.41, 95 % CI 1.18, 1.70)). Pneumococcal disease was
      highest in winter periods and coincided with influenza activity. The proportion
      of penicillin and erythromycin non-susceptible isolates increased from 4.2% in
      1992 to 12.6% in 1999 and from 5.6% in 1994 to 16.3% in 1999 respectively. Our
      data confirm the substantial and increasing disease burden from pneumococcal
      disease and rise in prevalence of antibiotic non-susceptibility among pneumococci
      in Scotland. Continued surveillance of groups at increased risk for pneumococcal
      disease and the antibiotic susceptibility and serotype distribution of isolates
      are important to develop appropriate policies for the prevention of pneumococcal
      disease in Scotland.

PMID- 12002531
TI  - Prevalence of moderate penicillin resistant invasive Neisseria meningitidis
      infection in Scotland, 1994-9.
AB  - We examined the serological characteristics of 774 invasive meningococcal
      isolates collected through an active laboratory-based surveillance system in
      Scotland from 1994 to 1999. Of these, 72-73% of isolates were tested for
      susceptibility to several antimicrobial agents. Meningococci with high-level
      resistance to sulphadiazine had a prevalence of 10% and incidence of 0.22 per
      100,000 population. High-level resistance to penicillin and other antibiotics was
      not detected. The prevalence of moderate penicillin resistant meningococci was
      8.3%. There was no increase in moderate penicillin resistant meningococcal
      isolates during the study period, but there were temporal and geographic
      variations. The estimated incidence of moderate penicillin resistant meningococci
      was 0.15 per 100,000 population. High and low incidence of moderate penicillin
      resistant meningococci appeared to correlate with the number of doses of
      penicillin prescribed in some geographic locations. The majority of moderate
      penicillin resistant isolates belonged to serogroups B (52.2%) and C (39.2%).
      However, the prevalence of moderate penicillin resistance in serogroup W135 was
      substantially higher (51.7%) than serogroups B (7.8%) and C (7.6%). Serogroup
      W135 accounted for a higher proportion of moderate penicillin resistance (8.7%)
      than disease (1%). There was no predominant penicillin resistant serotype/subtype
      within any serogroup. Constant surveillance is necessary to monitor the emergence
      and spread of resistance and to guide appropriate public health interventions in
      preventing drug resistant meningococci.

PMID- 12002532
TI  - Multilocus sequence typing of Neisseria meningitidis directly from cerebrospinal
      fluid.
AB  - MLST typing of Neisseria meningitidis directly from clinical material was
      introduced in the National Reference Laboratory for Meningococcal Infections in
      Prague. Four cerebrospinal fluid samples were obtained from patients with
      suspected meningococcal invasive disease. In all samples, all classical
      laboratory methods gave negative results and the only positive method was PCR,
      which revealed Neisseria meningitidis group C (two specimens) and group B (two
      specimens), respectively. MLST performed directly from cerebrospinal fluid
      revealed that the strains causing the two group C infections were of sequence
      type (ST) 11, while the two group B infections were characterized as ST-32 and ST
      33 respectively. Multi-locus sequence typing of meningococci directly from
      clinical material offers the opportunity to improve further the surveillance of
      meningococcal disease and has now been introduced into the routine portfolio of
      tests employed at the national reference laboratory of the Czech Republic.

PMID- 12002533
TI  - Serological diagnosis of pertussis: evaluation of IgA against whole cell and
      specific Bordetella pertussis antigens as markers of recent infection.
AB  - In Australia, notification of pertussis cases in older children or adults has
      increased significantly in recent years. In most cases, laboratory diagnosis is
      based only on a positive serological test for IgA antibody against whole cell
      Bordetella pertussis. During a 3-month period, 318 consecutive sera submitted for
      diagnosis of pertussis were tested for IgA antibody against whole cell (WC)
      sonicated B. pertussis, pertussis toxin (PT), filamentous haemagglutinin (FHA)
      and pertactin (PRN). Results of one or more of these tests were positive in sera
      from 175 subjects and clinical information was obtained by telephone interview
      from 90 subjects. Using a clinical case definition as the reference standard, the
      sensitivities of the four IgA assays were variable but quite low (24-64%), but
      the specificities were high (93-98%). For diagnosis of pertussis in subjects with
      a compatible clinical illness, these and other findings support the use of
      serological testing for IgA antibody.

PMID- 12002534
TI  - A method for adjusting gender bias in neonatal tetanus reports in Egypt 1991.
AB  - Reports of neonatal tetanus (NT) disease, common in developing countries, often
      suffers from gender bias because male infants are brought to health facilities
      while females are attended at home. Using existing health data we applied
      reasonable assumptions to estimate the true incidence of NT economically. To
      adjust for gender disparities in national reporting, we ignored the number of
      female NT cases and doubled the number for males. Governorates with similar
      demographic risk profiles for NT were assigned to one of six groups. The highest
      incidence rate within the group was determined and applied to the number of live
      births represented by the group. Other internal data comparisons were done to
      support our estimate that the male:female ratio of NT incidence was far less than
      the reported 412:1. In 1991, the male: female ratio of NT cases was 4.12:1.
      Decreasing the male: female ratio to 1:1 decreased sensitivity to a 62% estimate.
      Further adjusting for assumed under-reporting by governorates based on population
      profiles yielded a reporting sensitivity of 40%. Estimated male and female age
      specific NT mortality rates from available data supported the assumption that NT
      mortality ratios are less than 4.12:1. This report, therefore, describes a
      unique, economical method to estimate the incidence of a disease assumed to be
      affected by gender biases in the reporting system. The method relies on two
      assumptions: that the true NT male:female ratio is close to 1:1 and that
      populations with similar demographics within a country should have similar
      incidence rates of NT.

PMID- 12002535
TI  - The molecular epidemiology of tuberculosis in inner London.
AB  - The study used DNA fingerprint typing (spoligotyping and Heminested-lnverse-PCR)
      of Mycobacterium tuberculosis from all culture-confirmed inner London patients
      over a 12-month period to describe transmission. The methodology was evaluated by
      comparison with standard IS6110 typing and by examining its ability to identify
      known household clusters of cases. Isolates sharing indistinguishable typing
      patterns using both techniques were defined as clustered. Clusters were
      investigated to identify epidemiological links. The methodology showed good
      discriminatory power and identified known household clusters of cases. Of 694
      culture-confirmed cases, 563 (81%) were typed. Eleven (2%) were due to laboratory
      cross-contamination and were excluded. Of the remaining 552 isolates 148 (27%)
      were clustered. Multivariate analysis indicated that clustering was more common
      in those with pulmonary smear positive disease (P < 0.02); those born in the
      United Kingdom (P < 0.0003) and in patients living in south London (P = 0.02).
      There was also a trend towards clustering being more common in those not known to
      have HIV infection (P = 0.051). The results suggest that in inner London, recent
      local transmission makes an important contribution to notification rates.

PMID- 12002536
TI  - Detection of delayed vaccinations: a new approach to visualize vaccine uptake.
AB  - For the prevention of pertussis and invasive Haemophilus influenzae type b (Hib)
      infections, each with a peak for mortality and serious complications in the first
      year of life, early vaccination is important and needs adequate monitoring. In a
      1999 national coverage survey the timing of uptake of these vaccines in German
      children was therefore assessed conventionally at defined age thresholds and with
      a new adaptation of the Kaplan-Meier (KM) method estimating immunization uptake
      over time by 1 minus the survival function s(t). Only 6% and 9% of children were
      vaccinated against pertussis and Hib in accordance with the national recommended
      primary vaccination schedule. Coverage levels for the primary vaccination course
      of 50% and 90% were attained for pertussis after 6.6 and 16.3 months respectively
      and for Hib after 7.0 and 24.3 months. These estimates were only possible with
      the KM method which proved useful to monitor vaccination programmes and will
      allow the comparison of vaccination uptake in different populations.

PMID- 12002537
TI  - Quantification of transmission in one-to-one experiments.
AB  - We study the statistical inference from data on transmission obtained from one-to
      one experiments, and compare two algorithms by which the reproduction ratio can
      be quantified. The first algorithm, the transient state (TS) algorithm, takes the
      time course of the epidemic into account. The second algorithm, the final size
      (FS) algorithm, does not take time into account but is based on the assumption
      that the epidemic process has ended before the experiment is stopped. The FS
      algorithm is a limiting case of the TS algorithm for the situation where time
      tends to infinity. So far quantification of transmission has relied almost
      exclusively on the FS algorithm, even if the TS algorithm would have been more
      appropriate. Its practical use, however, is limited to experiments with only a
      few animals. Here, we quantify the error made when the FS algorithm is applied to
      data of one-to-one experiments not having reached the final size. We conclude
      that given the chosen tests, the FS algorithm underestimates the reproduction
      ratio R0, is liberal when testing H0: R0 > or = 1 against H1: R0 < 1, is
      conservative when testing H0: R0 < or = 1 against H1: R0 > 1 and calculates the
      same probability as the TS algorithm when testing H0: R(0-control) = R(0
      treatment) against H1: R(0-control) > R(0-treatment) We show how the power of the
      test depends on the duration of the experiments and on the number of replicates.
      The methods are illustrated by an application to porcine reproductive and
      respiratory syndrome virus (PRRSV).

PMID- 12002538
TI  - Clinical effectiveness of conventional influenza vaccination in asthmatic
      children.
AB  - Influenza immunization rates among young asthmatics remain unsatisfactory due to
      persistent concern about the impact of influenza and the benefits of the vaccine.
      We assessed the effectiveness of the conventional inactivated trivalent sub-unit
      influenza vaccine in reducing acute respiratory disease in asthmatic children. We
      conducted a two-season retrospective cohort study covering the 1995-6 and 1996-7
      influenza outbreaks in 22 computerized primary care practices in The Netherlands.
      In total, 349 patients aged between 0 and 12 years meeting clinical asthma
      criteria were included; 14 children were lost to follow-up in the second season.
      The occurrence of physician-diagnosed acute respiratory disease episodes
      including influenza-like illness, pneumonia. bronchitis, bronchiolitis, asthma
      exacerbation and acute otitis media in vaccinated and unvaccinated children were
      compared after adjustments for age, prior health care and medication use. The
      occurrence of acute respiratory disease in unvaccinated children was 28% and 24%
      in the 1995-6 and 1996-7 season, respectively, and was highest in children under
      6 years of age (43%). The overall pooled clinical vaccine effectiveness was 27%
      (95% confidence interval -7 to 51%, P = 0.11) after adjustments. A statistically
      higher vaccine protectiveness of 55% (95% CI 20-75%, P = 0.01) was observed among
      asthmatics under 6 years of age compared with -5% in older children (95% CI -81
      to 39%). The occurrence of acute respiratory disease among asthmatic children
      during influenza epidemics is very high, notably in the youngest. Influenza
      vaccination may reduce morbidity in asthmatic infants and pre-school children.
      However, larger, preferably experimental, studies are needed to establish the
      benefits of vaccination, notably in older asthmatic children.

PMID- 12002539
TI  - Assessment of the factors associated with flavivirus seroprevalence in a
      population in Southern Vietnam.
AB  - Dengue and Japanese encephalitis flaviviruses cause severe disease and are
      hyperendemic in southern Vietnam. This study assesses associations between
      sociodemographic factors and flavivirus seroprevalence in this region. Sera were
      collected from 308 community and hospital-based subjects between April 1996 and
      August 1997 and tested with an indirect ELISA. The factors associated with
      seroprevalence were assessed using multivariate logistic regression. In this
      first report of adjusted prevalence odds ratios (POR) for flavivirus infection in
      Vietnam, seropositivity was associated with increasing age in children (multiple
      regression coefficients for a child compared to an adult = -4.975 and for age in
      children = 0.354) and residence in the city compared to surrounding rural
      districts. The association with age indicates that subjects were most likely to
      have acquired infection in early childhood. This is key to the design of
      Vietnamese health education and immunization programmes.

PMID- 12002540
TI  - Prevalence of and risk factors for HIV infection in blood donors and various
      population subgroups in Ethiopia.
AB  - The aim was to determine the prevalence of HIV infection and risk factors for HIV
      infection in various population subgroups in Ethiopia. Serum panels from blood
      donors (n = 2610), from various population subgroups in Ethiopia were tested for
      anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for
      confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs.
      155/2610 (5.9%) blood donors were HIV-1 infected. Of pregnant women, 84/797
      (10.5%) were HIV-1 infected, and 1/797 (0.1%) was HIV-2 infected. 1/240 (0.4%)
      individuals from the rural population were HIV-1 infected. 198/480 (41.3%) female
      attendees, and 106/419 (25.3%) male attendees at sexual transmitted disease (STD)
      clinics were HIV-1 infected. One (0.2%) male, and 2 (0.4%) female STD patients
      were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of
      HIV-1 infection varied from 0.4% among urban residents to 25.3-41.3% among STD
      attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects.
      Risky sexual behaviour is significantly associated with HIV-infection in
      Ethiopia.

PMID- 12002541
TI  - Vaccination against hepatitis B in low endemic countries.
AB  - A mathematical model that takes transmission by sexual contact and vertical
      transmission into account was employed to describe the transmission dynamics of
      hepatitis B virus (HBV) and vaccination against it. The model is an extension of
      a model by Williams et al. (Epidemiol Infect 1996: 116; 71-89) in that it takes
      immigration of hepatitis B carriers from countries with higher prevalence into
      account. Model parameters were estimated from data from The Netherlands where
      available. The main results were that, given the estimates for the parameters
      describing sexual behaviour in The Netherlands, the basic reproduction number R0
      is smaller than 1 in the heterosexual population. As a consequence, the
      immigration of carriers into the population largely determines the prevalence of
      HBV carriage and therefore limits the possible success of universal vaccination.
      Taking into account the prevalence of hepatitis B carriage among immigrants and
      an age-dependent probability of becoming a carrier after infection, we estimate
      that a fraction of between 5 and 10% of carrier states could be prevented by
      universal vaccination.

PMID- 12002542
TI  - Antibodies in crevicular fluid: an epidemiological tool for investigation of
      waterborne disease.
AB  - A significant challenge in the epidemiological investigation of recreational
      waterborne disease is the establishment of a definite association between
      exposure to a contaminated water and infection. An increase in specific
      antibodies as a result of infection is a potent measure of disease exposure and
      its determination would enhance epidemiological studies of waterborne diseases.
      We report on the automated detection of HAV antibodies in crevicular fluid and
      its use in a field study. The method is easy to use, non-invasive, could be
      applied to volunteers of all ages and is comparable in sensitivity to serological
      procedures. Application to an epidemiological study of water recreationalists
      demonstrated that surfers were three times more likely to be immune to hepatitis
      A virus than either wind-surfers or a control group without recreational water
      contact.

PMID- 12002543
TI  - Tula hantavirus in Belgium.
AB  - European common voles (Microtus arvalis), captured in Belgium in 1999, were
      proven by molecular as well as by serological techniques to be infected with Tula
      hantavirus (TULV). This is the first evidence for the presence of TULV in this
      country. No indication of spill-over infections of Puumala virus, known to be
      highly endemic among bank voles (Clethrionomys glareolus) within the same
      geographical regions as the trapped TULV-infected common voles, was observed.
      Together with previous reports on the circulation of TULV in eastern/central
      Europe, this finding suggests a more wide-spread circulation of this hantavirus
      serotype throughout the continent.

PMID- 12002544
TI  - Studies on the epidemiology of bluetongue virus in China.
AB  - Sentinel herds of large ruminants were established at five centres in Yunnan
      Province, Peoples Republic of China, between 1995 and 1997. The application of a
      sensitive antigen capture ELISA to facilitate virus isolation procedures led to
      the isolation of 108 strains of bluetongue (BLU) virus. Serotypes isolated
      included types 1, 2, 3, 4, 9, 11, 12, 15, 16, 21 and 23. Virus transmission
      occurred over a period of 1-3 months at each of the four positive sites, giving
      an overall BLU virus transmission period for the province of 5 months, from early
      June to early November. The greatest level of transmission took place in July and
      August. The duration of viraemia in individual animals varied from 1 to 7 weeks,
      with a mean calculated for each serotype between 6 and 20 days. The study
      represents the first detailed investigation of the epidemiology of BLU in China
      utilizing sentinel herds.

PMID- 12002545
TI  - Transmission patterns of African horse sickness and equine encephalosis viruses
      in South African donkeys.
AB  - African horse sickness (AHS) and equine encephalosis (EE) viruses are endemic to
      southern Africa. AHS virus causes severe epidemics when introduced to naive
      equine populations, resulting in severe restrictions on the movement of equines
      between AHS-positive and negative countries. Recent zoning of South Africa has
      created an AHS-free zone to facilitate equine movement, but the transmission
      dynamics of these viruses are not fully understood. Here, we present further
      analyses of serosurveys of donkeys in South Africa conducted in 1983-5 and in
      1993-5. Age-prevalence data are used to derive estimates of the force of
      infection, A. For both viruses, A was highest in the northeastern part of the
      country and declined towards the southwest. In most of the country, EE virus had
      a higher transmission rate than AHS. The force of infection increased for EE
      virus between 1985 and 1993, but decreased for AHS virus. Both viruses showed
      high levels of variation in transmission between districts within the same
      province, particularly in areas of intermediate transmission. These data
      emphasize the focal nature of these viruses, and indicate areas where further
      data will assist in understanding the geographical variation in transmission.

PMID- 12002546
TI  - Isotype specific ELISAs to detect antibodies against swine vesicular disease
      virus and their use in epidemiology.
AB  - Isotype specific ELISAs to detect antibodies against swine vesicular disease,
      which may help to estimate the moment of infection, were developed and validated
      on sera from pigs experimentally infected with four different isolates of swine
      vesicular disease virus. Virus specific IgM antibodies could be detected from
      days 3-49 and occasionally up to day 91 after infection. IgG1 antibodies were
      first detected at day 8 and IgG2 at day 11. IgA antibodies coincided with IgG1
      antibodies, but antibody titres varied widely. From the results obtained with the
      sera from the experimentally infected pigs, we calculated the day at which 50% of
      the pigs had become positive (D50). A D50 of 5, 4, 12, 12 and 24 days was
      calculated, respectively, for the appearance of antibodies in the virus
      neutralization test, the IgM, total IgG, IgG1 and IgG2 ELISA. A D50 of 49 days
      was calculated for the disappearance of IgM antibodies. The isotype specific
      ELISAs proved to be valuable tools to study the epidemiology of the disease.

PMID- 12002547
TI  - Rate of inter-herd transmission of classical swine fever virus by different types
      of contact during the 1997-8 epidemic in The Netherlands.
AB  - In this study we quantified the rate at which classical swine fever had been
      transmitted by several different types of inter-herd contact during the 1997-8
      epidemic in The Netherlands. During that epidemic 428 CSFV-infected pig herds
      were detected, 403 of which were include in this study. The estimated rates of
      transmission were 0.065 per shipment of live pigs, 0.011 per contact by a pig
      transportation lorry, 0.0068 per person contact, 0.0007 per dose of semen, 0.0065
      per contact with a potentially contaminated pig assembly point, 0.027 per week
      per infected herd within a radius of 500 metres and 0.0078 per week per infected
      herd at a distance between 500 and 1000 metres. These transmission rates can be
      used to optimize the strategy to stop future epidemics of CSF in The Netherlands.
      In addition, the analysis demonstrated in this paper, can be used to quantify
      CSFV transmission rates from other epidemics.

PMID- 12002548
TI  - Within- and between-pen transmission of Classical Swine Fever Virus: a new method
      to estimate the basic reproduction ratio from transmission experiments.
AB  - We present a method to estimate basic reproduction ratio R0 from transmission
      experiments. By using previously published data of experiments with Classical
      Swine Fever Virus more extensively, we obtained smaller confidence intervals than
      the martingale method used in the original papers. Moreover, our method allows
      simultaneous estimation of a reproduction ratio within pens R0w and a modified
      reproduction ratio between pens R'0b. Resulting estimates of R0w and R'0b for
      weaner pigs were 100 (95% CI 54.4-186) and 7.77 (4.68-12.9), respectively. For
      slaughter pigs they were 15.5 (6.20-38.7) and 3.39 (1.54-7.45), respectively. We
      believe, because of the smaller confidence intervals we were able to obtain, that
      the method presented here is better suited for use in future experiments.

PMID- 12002549
TI  - Natural aerosol transmission of foot-and-mouth disease virus to pigs: minimal
      infectious dose for strain O1 Lausanne.
AB  - Foot-and-mouth disease virus (FMDV) can spread by a variety of mechanisms,
      including, under certain circumstances, by the wind. Simulation models have been
      developed to predict the risk of airborne spread of FMDV and have played an
      important part in decision making during emergencies. The minimal infectious dose
      of FMDV for different species by inhalation is an important determinant of
      airborne spread. Whereas the doses for cattle and sheep have been quantified,
      those for pigs are not known. The objective of the study was to obtain that data
      in order to enhance the capability of simulation models. Under experimental
      conditions, forty pigs were exposed individually to naturally generated aerosols
      of FMDV, strain O1 Lausanne. The results indicated that doses under 100 TCID50
      failed to infect pigs but doses of approximately 300 TCID50 caused short-term sub
      clinical infection. The calculations suggested that a dose of more than 800
      TCID50 is required to cause infection and typical disease.

PMID- 12002550
TI  - Further studies to quantify the dose of natural aerosols of foot-and-mouth
      disease virus for pigs.
AB  - Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms,
      including wind. Simulation models, developed to predict the risk of airborne
      spread, have played an important part in decision making in some outbreaks. The
      amount of airborne virus excreted as well as the minimal infectious dose (MID) of
      FMDV for different species are important determinants of airborne spread. The
      objective of this study was to obtain data for the O1 Lausanne, O SKR 2000 and O
      UKG 2001 strains of FMDV to enhance the capability of such models. Pigs were
      exposed to naturally generated aerosols of the three strains using an
      experimental design which delivered high doses of the two strains O1 Lausanne and
      O SKR 2000 over a short period, or of the O UKG 2001 strain over an extended
      period. The average excretion of the O1 Lausanne strain was 10(6.4) TCID50 per
      pig per hour. The excretion of the O SKR 2000 strain averaged 10(5.8) and the O
      UKG 2001 strain 10(6.1) TCID per pig per 24 h. The results show that the previous
      estimate of 'above' 800 TCID50 as the MID50 for the O1 Lausanne strain is a
      considerable under-estimate and that the real dose may be as high as 6000 TCID50.
      A dose of around 650 TCID50 of the O SKR 2000 strain failed to infect any pigs.
      Thus, the aerosol MID50 for pigs for this isolate is at least 1000 TCID50 and
      likely to be as high or higher than the O1 Lausanne strain. The exposure of pairs
      of recipient pigs kept physically separated from donor pigs in a series of rooms
      to aerosol exposure doses of the O UKG 2001 strain of around 50 TCID50 per min
      for 24-48 h failed to infect any of eight pigs. Thus, the present experiment
      confirms our previous findings that pigs, compared to cattle and sheep, are
      relatively resistant to infection with airborne FMDV.

PMID- 12002551
TI  - Dose-response relationships for foot and mouth disease in cattle and sheep.
AB  - The relationships between the inhaled dose of foot and mouth disease virus and
      the outcomes of infection and disease were examined by fitting dose-response
      models to experimental data. The parameters for both the exponential and beta
      poisson models were estimated using maximum likelihood and Bayesian methods. The
      median probability of infection given a single inhaled TCID50 was estimated to be
      0.031 with 95% Bayesian credibility intervals (CI) of 0.018-0.052 for cattle, and
      0.045 (CI = 0.024-0.080) for sheep. These estimates were used to construct dose
      response curves and uncertainty distributions for use in quantitative risk
      assessments.

PMID- 12002552
TI  - IS200 fingerprinting of Salmonella enterica serotype Abortusovis strains isolated
      in Iran.
AB  - Salmonella enterica serovar Abortusovis is one of the most common pathogens
      responsible for abortion in sheep. In Iran, the spread of Abortusovis is highly
      dependent on the nomadic life style. In this study we performed IS200
      fingerprinting to identify the clonal lines circulating in Iran. All the isolates
      contained 4 or 5 copies of the transposon and could be classified in 4 genotypes.
      A single genotype was highly prevalent and very likely it has circulated in Iran
      since 1970. All the isolates showed a high degree of relatedness.

PMID- 12002553
TI  - Pyrazinamide resistance associated with pncA gene mutation in Mycobacterium
      tuberculosis in Japan.
AB  - Thirty Japanese clinical isolates of Mycobacterium tuberculosis were analysed by
      pyrazinamide susceptibility testing and pyrazinamidase assay, as well as
      polymerase chain reaction for single-strand conformational polymorphism and
      direct sequencing of the gene encoding pyrazinamidase (pncA). All sensitive
      isolates showed pyrazinamidase activity and a wild-type pncA gene, but three
      resistant isolates had pncA gene mutations and lacked pyrazinamidase activity.
      The latter isolates showed a minimum inhibitory concentration of at least 100
      mg/l by the 7H10 agar proportion method and 400 mg/l by the 7H9 liquid medium
      method. Isolate 28 showed T-to-C change at position 11, leading to Leu4 --> Ser
      substitution; isolate 29 had an 8-bp deletion from position 382; and isolate 30
      had A-to-C change at position 29, leading to Gln10 --> Pro substitution. The
      deletion has not been described previously. This is the first demonstration of
      pncA gene mutations in PZA-resistant M. tuberculosis strains isolated from
      Japanese patients.

PMID- 12002554
TI  - Long term immunity in African cattle vaccinated with a recombinant capripox
      rinderpest virus vaccine.
AB  - Cattle were vaccinated with a recombinant capripox-rinderpest vaccine designed to
      protect cattle from infection with either rinderpest virus (RPV) or lumpy skin
      disease virus (LSDV). Vaccination did not induce any adverse clinical responses
      or show evidence of transmission of the vaccine virus to in-contact control
      animals. Approximately 50% of the cattle were solidly protected from challenge
      with a lethal dose of virulent RPV 2 years after vaccination while at 3 years
      approx. 30% were fully protected. In the case of LSDV, all of 4 vaccinated cattle
      challenged with virulent LSDV at 2 years were completely protected from clinical
      disease while 2 of 5 vaccinated cattle were completely protected at 3 years. The
      recombinant vaccine showed no loss of potency when stored lyophylized at 4
      degrees C for up to 1 year. These results indicate that capripoxvirus is a
      suitable vector for the development of safe, effective and stable recombinant
      vaccines for cattle.

PMID- 12002555
TI  - Recruitment of older participants in frailty/injury prevention studies.
AB  - Despite the lifelong health benefits of physical activity, frailer older adults
      have typically been excluded from studies promoting more active lifestyles. This
      study documents the recruitment process and costs from a multisite study to
      identify effective strategies for recruiting older adults in frailty/injury
      prevention research. Randomized controlled clinical trials were conducted at 7
      sites; an 8th site was a compliance study. Interventions reflected center- and
      home-based health promotion programs. Site objectives, eligibility criteria, and
      contact and screening methods were obtained from manuals of operation.
      Recruitment results (number screened, eligibility rates, randomized to screened
      ratios) were ascertained from recruitment data. Sites furnished estimated
      recruitment costs (nonlabor expenses, investigator and staff time, fringe
      benefits) up to signing the consent form. The sites targeted diverse populations
      and sample sizes. The majority revised recruitment methods to meet their
      recruitment goals. Most sites estimated costs of recruitment at over $300 per
      participant randomized. Recruitment costs were affected by staff time spent
      alleviating concerns about participants' health, essential interactions with
      family members, and arranging for transportation. Neither frailty nor
      intervention intensity was found to be a major predictor of recruitment outcomes.
      Recruitment expense was associated with selection criteria and frailty status of
      the target population. Older people can be successfully recruited into beneficial
      health promotion programs, but it is often challenging. In planning health
      promotion studies, investigators need to be aware of the numbers of older people
      they may need to screen and different strategies for increasing recruitment
      success.

PMID- 12002556
TI  - Personal competence skills, distress, and well-being as determinants of substance
      use in a predominantly minority urban adolescent sample.
AB  - Several previous studies have investigated the relationship between psychological
      distress and substance use among youth. However, less research has investigated
      the potentially protective role of psychological well-being on adolescent
      substance use, and the extent to which personal competence skills may promote
      well-being. The present study examined personal competence skills, psychological
      distress and well-being, and adolescent substance use over a 3-year period in a
      predominantly minority sample of urban students (N = 1,184) attending 13 junior
      high schools in New York City. Structural equation modeling indicated that
      greater competence skills predicted less distress and greater well-being over
      time. Although psychological well-being was associated with less subsequent
      substance use, distress did not predict later substance use. Findings indicate
      that competence skills promote resilience against early stage substance use in
      part by enhancing psychological well-being, and suggest that school-based
      prevention programs should include competence enhancement components in order to
      promote resilience.

PMID- 12002557
TI  - Influence of a family program on adolescent smoking and drinking prevalence.
AB  - Reducing the prevalence of adolescent cigarette smoking and alcohol drinking are
      public health goals of the United States. Although families have strong influence
      on their children, few randomized studies have examined whether family-directed
      programs influence those behaviors in general universal populations. This paper
      reports findings from an evaluation of a family program that features the mailing
      of four booklets to adult family members with follow-up telephone calls by health
      educators. A national sample of adolescent-parent pairs and a randomized
      experimental design were used to evaluate the program. Baseline users and
      nonusers of those substances were considered simultaneously in analyses so that
      program influences on smoking and drinking prevalence could be examined. The
      findings suggest that the program significantly reduced the prevalence of smoking
      cigarettes and drinking alcohol among adolescents. These findings are discussed
      in the context of earlier reports of research on the family program and
      implications for public health.

PMID- 12002558
TI  - Implementation and evaluation of a cognitive-behavioral intervention to prevent
      problem behavior in a disorganized school.
AB  - We assessed the effectiveness of two realizations of cognitive-behavioral
      instruction in an inner-city middle school with high rates of absenteeism, low
      staff morale, and chronic low academic achievement. Implementation measures
      showed that 68% of intended instruction was delivered in the first realization.
      Self-report measures showed improved school conduct, less victimization in
      school, and more positive peer associations for the treatment group than for the
      comparison group at the end of the school year. Treatment students were less
      likely to leave the school than were comparison students, but were more often
      absent and tardy. Implementation was poorer in the second realization, and there
      were no treatment-comparison differences on self-reports or teacher ratings, but
      treatment students less often left the school. Difficulties in conducting
      instruction in difficult settings may limit the effectiveness of otherwise
      efficacious interventions. Specific intervention programs may offer minimal
      benefits if more basic school improvements are not achieved.

PMID- 12002559
TI  - Tobacco industry youth tobacco prevention programming: a review.
AB  - This review provides a description of the youth tobacco prevention activities of
      the Tobacco Institute and the 6 largest U.S. tobacco companies. A computer search
      of PsycINFO and MedINFO from 1984 to the present, and a concurrent web metasearch
      of DogPile.com under the terms "tobacco industry" and "youth smoking prevention"
      was completed. All journal articles and web pages that discussed tobacco industry
      youth tobacco prevention program methods were examined. Programming was examined
      by whether it addressed 13 types of components that constitute effective tobacco
      use prevention. It is concluded that self-generated tobacco industry programming
      is lacking several of the types of components that are contained in effective
      programming. Providing financial support of nonindustry programming greatly
      improves this effort; however, the concept of tobacco industry involvement in
      youth tobacco prevention needs continued examination.

PMID- 12002560
TI  - Pubertal timing and the onset of substance use in females during early
      adolescence.
AB  - The goal of this study is to examine in detail the relationship between pubertal
      timing and substance use onset using a sample of females from The National
      Longitudinal Study of Adolescent Health. The sample includes 966 females who were
      in 7th grade at Wave 1 and 8th grade at Wave 2. Participants in the sample are
      approximately 69% White, 20% African American, 4% Asian or Pacific Islander, 2%
      American Indian, 4% other, of Hispanic origin, and 1% other, not of Hispanic
      origin. Twenty percent of the females were identified as early maturers based on
      self-reports of body changes (increased breast size and body curviness) measured
      in 7th grade. These participants are hypothesized to be at increased risk for
      substance use onset. Important differences in substance use onset were found
      between early maturers and their on-time and late-maturing counterparts. During
      7th grade, females in the early-maturing group are three times more likely to be
      in the most advanced stage of substance use (involving alcohol use, drunkenness,
      cigarette use, and marijuana use) than are those in the on-time/late group.
      Prevalence rates indicate that early maturers are more likely to have tried
      alcohol, tried cigarettes, been drunk, and tried marijuana. Prospective findings
      show that early developers are significantly more likely to transition out of the
      "No Substance Use" stage between 7th and 8th grade (47% for early developers vs.
      22% for on-time and late developers). In addition, early developers are more
      likely to advance in substance use in general, regardless of their level of use
      at Grade 7.

PMID- 12002561
TI  - New views on fungal evolution based on DNA markers and the fossil record.
AB  - Molecular markers have facilitated a better understanding of the evolution of
      fungi. Molecular phylogenetics determined the closest relatives of fungi and
      defined natural groups within the true fungi. The impact of molecular markers on
      the population biology of fungi has been enormous, helping to define cryptic
      species and elucidating fungal breeding biology. The interaction between
      molecular phylogenetics and the fungal fossil record is discussed.

PMID- 12002562
TI  - Microbial transformation of chlorinated benzenes under anaerobic conditions.
AB  - Chlorobenzenes are reductively dechlorinated by anaerobic bacterial cultures
      obtained from sediments and sludge. Recently a strain was isolated that couples
      reductive dechlorination of chlorobenzenes with energy conservation. The results
      reviewed in this article suggest that additional anaerobic bacteria, thriving by
      dehalogenation of chlorobenzenes or chlorobiphenylic compounds, can be isolated.

PMID- 12002563
TI  - Variation in rRNA operon number as revealed by ribotyping of Bacillus anthracis
      strains.
AB  - Ribotyping of various Bacillus strains with one restriction enzyme (AccI)
      revealed significant similarity between Bacillus anthracis strains, Bacillus
      thuringiensis and Bacillus cereus strains, which are all members of the Bacillus
      cereus group. A further ribotyping study of 10 virulent and 8 attenuated B.
      anthracis strains, using 4 endonucleases and both 23S and 16S probes
      independently, was performed. The discrimination index D of Hunter and Gaston
      showed that the best combination for future large-scale ribotyping studies would
      be either the combination of AccI and 23S, or that of EcoRI and 16S. Depending on
      the B. anthracis strain analyzed 10 or 11 rRNA operons were found. In all cases,
      many strains were grouped into 2 to 3 patterns. Attenuated strains, including a
      laboratory-cured strain, yielded aberrant patterns.

PMID- 12002564
TI  - Characterization of plasmid MIP233 (IncHI3) of the H complex.
AB  - Plasmid MIP233, the unique member of the IncHI3 subgroup of the H incompatibility
      complex, is a large self-transferable plasmid encoding for sucrose utilization,
      the PacB character and resistance to tellurite. The current study examined
      whether pMIP233 conferred other putatively advantageous plasmid-encoded
      functions. Heavy metal studies revealed pMIP233 phenotypes of resistance to
      cadmium, cobalt, lead, zinc and nickel. Sequencing of random clones from a
      pMIP233 library revealed extensive homology with IS elements and genes involved
      in the metabolic processes demonstrated. Interestingly, pMIP233 did not appear to
      code for resistance to a wide range of antibiotics. pMIP233 is considered to be a
      metabolic plasmid.

PMID- 12002565
TI  - A gene coding for ornithine decarboxylase (odcA) is differentially expressed
      during the Mucor circinelloides yeast-to-hypha transition.
AB  - The differential display technique was used to identify genes from Mucor
      circinelloides involved in the yeast-to-hypha transition. Using a limited set of
      primer combinations, cDNA fragments corresponding to mRNAs differentially
      expressed during the dimorphic transition were isolated. Northern analyses showed
      that the accumulation of the transcript detected by hybridisation with one of the
      cDNA fragments increased during the transition and was undetectable at the
      mycelial stage. Sequence analysis and database searches of this fragment revealed
      high similarity to ornithine decarboxylase (ODC) encoding genes. The odcA gene of
      M. circinelloides was isolated from genomic and cDNA libraries and characterised.
      Electrophoretic karyotyping and hybridisations showed that the odcA gene is
      single-copy and linked to the leuA and rDNA genes. The single transcript detected
      (2.1 kb), was considerably longer than the deduced ORF. Through non-radioactive
      primer extension analysis four transcription initiation sites were mapped to
      positions -61, -167, -239 and -436 from the start codon. The ODC mRNA levels
      increased during the yeast-to-hypha transition, reaching a maximum at 120 min,
      which was accompanied by a rise in ODC enzymatic activity. The expression pattern
      of the odcA gene showed that in M. circinelloides the ODC levels are
      transcriptionally regulated, in contrast with other dimorphic fungi in which a
      post-transcriptional regulation has been proposed.

PMID- 12002566
TI  - Inhibition of 4-nitroquinoline-1-oxide genotoxicity by Bacillus strains.
AB  - The effect of 16 Bacillus strains from pharmaceutical probiotic preparations
      (Bacillus spp.) and collection (B. subtilis, B. firmus, B. megaterium, B.
      pumilus) on genotoxicity induced by the known mutagen 4-nitroquinoline-1-oxide (4
      NQO) was studied using the short-term bacterial assay SOS-chromotest. with
      Escherichia coli PQ37 as the tester organism. It was found that the activity of
      0.1 mM 4-NQO was reduced (P < 0.01) after coincubation with Bacillus suspensions
      (10(8) CFU/ml for 150 min at 37 degrees C). All isolates showed potential for
      deactivating 4-NQO, and genotoxicity inhibition ranged from 92.9 to 100%. There
      were no appreciable differences in behaviour observed among probiotic and
      collection strains or in relation to species. The observed antigenotoxicity was
      associated with a clear-cut modification of 4-NQO molecular characteristics.

PMID- 12002567
TI  - Feasibility of copper uptake by the yeast Pichia guilliermondii isolated from
      sewage sludge.
AB  - Copper is one of the most abundant toxic heavy metals in municipal wastewaters
      and, in consequence, in sewage sludge and compost. The ability of a strain of the
      yeast Pichia guilliermondii, which was isolated from sewage sludge, to eliminate
      copper has been evaluated, using both viable and nonviable biomass. It has been
      found that raising concentrations of copper affected both morphology and
      physiological parameters of the viable yeast, and it is thought that a process of
      bioaccumulation may be involved in its copper uptake. The growth rate of
      nonadapted cells decreased with increasing concentrations of copper, mainly due
      to a decrease in the biomass yield. The cells could be adapted by training with
      increasing copper concentrations up to 317.7 mg/l. This adaptation was an all-or
      nothing process: once cells had adapted, the biomass yield, metabolic flux and
      consequent growth rate were constant and independent of the external copper
      concentration. Also, it was determined that up to 20 mg of copper per gram of
      viable adapted biomass could accumulate from the medium (i.e., double the amount
      when using nonadapted viable biomass). Finally, adsorption data on nonviable
      cells were found to be well modeled by the Langmuir isotherm (qmax = 9.09 mg/g of
      biomass).

PMID- 12002568
TI  - Biofilm formation in Escherichia coli is affected by 3-(N-morpholino)propane
      sulfonate (MOPS).
AB  - In most natural environments, association with a surface in a structure known as
      a biofilm is the prevailing microbial life-style. Escherichia coli has been a
      useful model for the study of biofilm formation. Here we analyzed the amounts of
      biofilm formed when E. coli was cultured in the presence of MOPS [3-(N
      morpholino)propane sulfonatel. We used the "O'Toole and Kolter" method, which
      consisted of growing cells in PVC microtiter dishes and staining the formed
      biofilm with crystal violet. Our results showed that: 1) the addition of 100 mM
      MOPS to the rich Luria-Bertani (LB) medium increased the capacity of biofilm
      formation of several E. coli strains; and 2) the biofilm formed by cells growing
      in the presence of MOPS was more evident and well defined than that of cells
      cultured in LB-only medium. The improved ability of forming biofilms was
      maintained even for 60 h after removing MOPS from the medium, indicating that
      this improvement was due to a change in the metabolism of E. coli growing in the
      presence of MOPS or that, under these conditions, biofilm formation was favored.

PMID- 12002569
TI  - Ectopic pregnancy with uterine horn encapsulation in a cat.
AB  - A 4 x 7-cm free-floating cylindrical mass was found in the abdomen of a 2 1/2
      year-old domestic short-hair cat at ovariohysterectomy. The left uterine horn was
      absent. The mass contained 2 necrotic fetuses surrounded by tissue with the
      histologic appearance of uterine wall.

PMID- 12002570
TI  - Colonic perforation after corticosteroid and surgical treatment of intervertebral
      disk disease in a dog.
AB  - Colonic perforation after corticosteroid and surgical treatment of intervertebral
      disk disease in a dog Perforation of the distal segment of the descending colon,
      after corticosteroid and neurosurgical treatment for an intervertebral disk
      herniation, resulted in the death of a 3-year-old, male, Lhasa Apso. Initially,
      the dog was paraparetic in the hindlimbs, but became paraplegic after 4 days of
      conservative treatment. Corticosteroids were administered before referral and
      during decompressive hemilaminectomy. Six days after surgery, the dog had
      improved neurologically, but was depressed, anorectic, and vomiting.
      Abdominocentesis revealed septic peritonitis. The dog died shortly after a
      perforation in the descending colon was surgically corrected.

PMID- 12002571
TI  - Membrana nictitans gland cyst in a dog.
AB  - A cyst involving the gland of the 3rd eyelid was removed from an 8-year-old dog.
      Clinically the circumscribed mass resembled a pigmented neoplasm. Histologically
      the cyst was multiloculated, with homogeneous eosinophilic periodic acid-Schiff
      positive content. Melanin pigment was present in epithelial cells and cystic
      lumens. Protective functions of the 3rd eyelid were retained following excisional
      biopsy.

PMID- 12002572
TI  - Cryptosporidiosis in a pup.
AB  - Cryptosporidiosis is a coccidian parasitism which has been implicated as a cause
      of diarrhea in man and a variety of animals. Cryptosporidiosis was diagnosed in a
      one-week-old pup which had a history of acute diarrhea. Organisms, 2 to 3 mm in
      diameter, covered the microvillous border of intestinal epithelium.
      Ultrastructurally, the cryptosporidia had one or more nuclei with prominent
      nucleoli and abundant cytoplasmic endoplasmic reticulum. Cryptosporidia may have
      played a role in the enteritis seen in this pup but further studies are needed to
      establish its pathogenicity.

PMID- 12002573
TI  - Lumbar epidural chondrosarcoma in a dog treated by excision and chemotherapy.
AB  - A 5-year-old dog developed neurologic signs of thoracolumbar spinal cord
      dysfunction. The presence of an epidural mass which affected the electromyogram
      of the T-13 to L-3 spinal segments was demonstrated by myelography. Surgical
      removal was attempted. Examination of frozen and formalin-fixed tissues revealed
      the mass to be a chondrosarcoma. Doxorubicin hydrochloride was given every third
      week for a total of 6 doses following surgery. No signs of recurrence or
      metastases have been found for over 6 months. The differential diagnosis of
      epidural masses should include chondrosarcoma, even in the absence of vertebral
      lesions on plain radiographs, as in this case. Rapid diagnosis and aggressive
      therapy may have improved the prognosis.

PMID- 12002574
TI  - Peripheral neuropathy and hypotension in a diabetic dog.
AB  - Peripheral neuropathy and hypotension were found in a diabetic dog with profound
      weakness. Insulin therapy controlled the diabetes mellitus. As the blood glucose
      was normalized, the neurologic signs and hypotension resolved, suggesting a
      causal relationship.

PMID- 12002575
TI  - Progressive oropharyngeal dysfunction in a dog.
AB  - A dog with an acquired, progressive oropharyngeal dysphagia also had a myopathy
      neuropathy. It was clinically similar to criocopharyngeal achalasia, and could
      easily have been confused with it, even with fluoroscopic evaluation.
      Conservative medical therapy was instituted since cricopharyngeal myotomy could
      have caused severe aspiration and death. Resolution was apparently due to anti
      inflammatory therapy.

PMID- 12002576
TI  - Serum hyperviscosity syndrome associated with Ehrlichia canis infection in a dog.
AB  - A 10-year-old male Lhasa Apso was examined because of pyrexia, vomiting, weight
      loss, lethargy, and disorientation. The clinical and laboratory findings were
      supportive of a diagnosis of serum hyperviscosity syndrome associated with an
      Ehrlichia canis infection. After tetracycline therapy the serum hyperviscosity
      syndrome and E. canis infection were successfully resolved.

PMID- 12002578
TI  - Integrity and the veterinary profession.

PMID- 12002577
TI  - What is your diagnosis? Prepubic hernia involving the left kidney and loops of
      the intestine.

PMID- 12002579
TI  - Leptospirosis vaccination.

PMID- 12002580
TI  - FDA rejects extra-label drug use proposal.

PMID- 12002581
TI  - Council acts on House recommendations.

PMID- 12002582
TI  - Effects of doxapram in dogs given atropine and xylazine.

PMID- 12002583
TI  - Human/animal bond.

PMID- 12002584
TI  - Rules on hazardous materials.

PMID- 12002585
TI  - Steel jaw traps, HR 1797.

PMID- 12002586
TI  - Is arbitration for veterinarians?

PMID- 12002587
TI  - Fatal cerebrospinal disease caused by Baylisascaris procyonis in domestic
      rabbits.
AB  - Infection with Baylisascaris procyonis, the common roundworm of raccoons, was
      found to be the cause of an epizootic of fatal CNS disease in domestic rabbits
      (Oryctolagus cuniculus). Clinical signs included torticollis, ataxia, tremors,
      and falling. Gross lesions were limited to white, raised nodules (1 to 1.5 mm) on
      the epicardium, endocardium, and liver serosa, and they were found to be larval
      granulomas. Microscopic lesions included multifocal myocarditis, multifocal
      hemorrhagic tracks and associated necrosis and inflammation in the liver,
      multifocal eosinophilic myositis, focal nephritis, and mild interstitial
      pneumonia; larval granulomas were seen in the heart, liver, lung, and mandibular
      salivary gland. Lesions in the brain consisted of multifocal areas of necrosis
      and inflammation in the cerebrum, cerebellum, midbrain, and medulla, with
      accompanying perivascular leukocyte aggregates and neuronal and axonal
      degeneration. Large numbers of large ascarid larvae were seen in the brain.
      Epidemiologically, infection was linked to the use of contaminated straw from a
      barn used by raccoons. On the basis of this study as well as that of similar
      studies, it was concluded that barn use and contamination by raccoons may be an
      important source of infection of animals and possibly man with this parasite.

PMID- 12002588
TI  - Treatment of canine aural hematoma with an indwelling drain.
AB  - Aural hematomas in 9 dogs were managed by manual expression through stab
      incisions in the pinna and placement of indwelling silicone rubber drains,
      without compression bandaging. The drains were well tolerated. Seromas developed
      in 2 ears when the drains were removed at 7 and 10 days, but the seromas resolved
      when the drains were replaced. Healing without deformation of the pinna was
      obtained when the drains were maintained 13 to 28 days.

PMID- 12002589
TI  - Short-limbed dwarfism and ocular defects in the Samoyed dog.
AB  - A syndrome of short-limbed dwarfism and ocular defects was found in Samoyed dogs.
      The most prominent abnormalities were small stature and valgus deformity of the
      carpi. Radiographic evidence of retarded growth at the distal ulnar physis was
      apparent by 12 weeks of age. Ocular defects included cataracts and retinal
      detachment. Family studies and limited breeding experiments were consistent with
      an autosomal recessive mode of inheritance.

PMID- 12002590
TI  - Effects of modified protein diets in dogs with chronic renal failure.
AB  - A maintenance diet containing 44.4% dry weight protein and 2 reduced protein
      diets containing 17.2% and 8.2% dry weight protein were studied in dogs with
      induced chronic renal failure to determine effects on their (1) clinical status,
      (2) renal function, (3) electrolyte and acid-base balance, (4) divalent ion
      balance, (5) nutritional status, (6) hematologic status, and (7) hemostasis. A
      cross-over design of feeding was utilized so that the effect of diet could be
      studied in each dog at a known state of renal dysfunction and so that
      reversibility of effects could be determined. The inulin clearance rate was
      higher when the 44.4% protein diet was fed than when the 8.2% or 17.2% protein
      diets were fed. However, consumption of lower protein diets was associated with
      greater physical activity and reduction in serum urea nitrogen concentrations,
      compared with consumption of the 44.4% protein maintenance diet. Varying degrees
      of hyperchloremic metabolic acidosis developed in dogs fed the 8.2% and 17.2%
      protein diets. Reduced total serum protein and albumin concentrations, and
      hypercholesterolemia developed in dogs fed the 8.2% protein diet. All effects
      were reversible after diets were changed. It was concluded that diet-induced
      alterations in renal function associated with moderate dietary protein
      restriction did not adversely effect clinical and biochemical status of dogs with
      renal failure. It was unclear whether the clinical and biochemical changes
      observed with more severe protein restriction resulted from diet-induced changes
      in renal function.

PMID- 12002591
TI  - Fenbendazole treatment of pregnant bitches to reduce prenatal and lactogenic
      infections of Toxocara canis and Ancylostoma caninum in pups.
AB  - A granulated formulation of fenbendazole was tested in a total of 23 treated and
      control, pregnant, parasite-free Beagle bitches experimentally infected with
      Toxocara canis and Ancylostoma caninum. The drug was administered to each treated
      bitch once daily in canned dog food at a dosage of 50 mg/kg body weight. Each of
      2 treatment regimens tested was initiated on the 40th day of pregnancy. One
      regimen involved daily treatment continuing through the 14th postpartum day, and
      it resulted in 89% fewer ascarids and 99% fewer hookworms in pups born to
      medicated bitches, as compared with pups born to unmedicated controls. The other
      regimen of treatment, which was stopped on the day of parturition, was less
      effective in reducing ascarid and hookworm burdens (64% and 88% reductions,
      respectively). Three to 5 bitches from each of the treatment and control groups
      were allowed to whelp a 2nd litter without further treatment or further exposure
      to parasite infections. Hookworm burdens in 2nd-litter pups born of bitches that
      had initially received fenbendazole through the 14th postpartum day were
      significantly lower (P < 0.01; 85% reduction), when compared with the 2nd-litter
      control pups. All other parasite burdens were not significantly different. It was
      concluded that granulated fenbendazole is effective in reducing burdens of
      Ancylostoma caninum and Toxocara canis in newborn pups when the bitch is treated
      during the last third of pregnancy, especially when treatment (50 mg/kg/day)
      extends from the 40th day of pregnancy through the 14th postpartum day.

PMID- 12002592
TI  - Comparison of plasma aldosterone concentration among clinical status groups of
      dogs with chronic heart failure.
AB  - The plasma aldosterone concentration (PAC) among clinical status groups of 23
      dogs with chronic heart failure was compared at various times after diagnosis of
      the problem. Eighteen dogs admitted in New York Heart Association (NYHA) class IV
      clinical status had significant elevations in PAC (P<0.0001), when compared with
      clinically normal dogs. Five dogs admitted in NYHA class III status and 4 dogs
      that responded with a change to NYHA class III status had significant elevations
      in PAC (P<0.01), when compared with clinically normal dogs. In patients with NYHA
      class IV status, the PAC was significantly greater (P<0.01) than in patients in
      NYHA class III status. For patients with the poorest prognosis, ie, severe signs
      of NYHA class IV status, the PAC was not markedly different, when compared with
      that for patients with a favorable prognosis, ie, recent onset of signs of NYHA
      class IV status. Patients treated with captopril had significantly lower PAC
      after therapy (P<0.01), whereas patients treated with hydralazine had
      significantly higher PAC (P<0.05) after therapy. It was concluded that heart
      failure in the dog increases PAC, most likely because of renin-angiotensin
      aldosterone-system activation, and that the increase is related directly to the
      clinical status of the patient. Further, it was concluded that treatment of dogs
      in heart failure with captopril causes a decrease in circulating PAC, whereas
      treatment with hydralazine causes an increase in circulating PAC.

PMID- 12002593
TI  - Rabies induced in a cat by high-egg-passage Flury strain vaccine.
AB  - An adult male domestic short-hair cat developed posterior paralysis 22 days after
      being vaccinated for rabies with a high-egg-passage Flury strain vaccine
      currently approved for use in cats. A diagnosis of rabies was confirmed by mouse
      inoculations, and viral typing using a panel of monoclonal antibodies
      demonstrated that it was vaccine induced.

PMID- 12002594
TI  - Degenerative myelopathy in a family of Siberian Husky dogs.
AB  - Three closely related, Siberian Husky dogs had chronic progressive paresis and
      ataxia with muscle atrophy in the hindlimbs. Radiologic and myelographic
      examination of the spine revealed no abnormalities. On histologic examination,
      disseminated degeneration of the white matter, particularly in the thoracic
      segments, was seen. The clinical and pathological findings were similar to those
      described in aging large dogs with so-called degenerative myelopathy. The cause
      of this disease is unknown but the fact that these 3 Huskies were closely related
      suggest that hereditary factors may play a role.

PMID- 12002595
TI  - Potential-resolved electrochemiluminescence of ru(bpy)3(2+)/C2O4(2-) system on
      gold electrode.
AB  - The electrogenerated chemiluminescence of Ru(bpy)3(2+)/C2O4(2-) system on a pre
      polarized Au electrode was studied using a potential-resolved
      electrochemiluminescence (PRECL) method. Two anodic ECL peaks were observed at
      1.22 V (vs. SCE) (EP1), 1.41 V (vs. SCE) (EP2), respectively. The effects of the
      concentration of oxalate and Ru(bpy)3(2+), adsorbed sulphur, CO2, O2, pH of the
      solution and pretreatment of the Au electrode on the two PRECL peaks were
      examined. The surface state of the pre-oxidized gold electrode was also studied
      using the X-ray photoelectron spectroscopy (XPS) technique. Moreover, comparative
      studies on i-E and I-E curves were carried out and a possible mechanism involving
      both the catalytic and the direct electro-oxidation pathways was proposed for the
      ECL of Ru(bpy)3(2+)/C2O4(2-) system. EPI is attributed to the Ru(bpy)3(2/3+)
      reaction catalysed by C2O4(2-) to generate Ru(bpy)3(2+)*. EP2 is likely because
      C2O4(2-) was oxidized at the electrode to form CO2(-)*, followed by reaction with
      Ru(bpy)3(3+) to generate Ru(bpy)3(2+)*.

PMID- 12002596
TI  - Simultaneous detection of two verotoxin genes using dual-label time-resolved
      fluorescence immunoassay with duplex PCR.
AB  - Verotoxin (VT) produced by several Escherichia coli serotypes causes haemorrhagic
      colitis and has been associated with haemolytic uraemic syndrome in humans. Two
      types of verotoxin are known. Conventional diagnosis of verotoxin-producing
      Escherichia coli (VTEC) is conducted after isolation of bacteria from clinical
      specimens, followed by serological determination and identification of VTs. This
      method is complicated and time-consuming. Recently, rapid, direct immunological
      methods for identification of VTEC, i.e. immunochromatography and latex
      agglutination, have been developed. However, these techniques continue to suffer
      from limited sensitivity and a lack of specificity. These difficulties arise from
      the fact that the antibody used in these procedures reacts exclusively with the
      O157 antigen; moreover, VTEC strains with non-O157 antigens, such as O26, O103
      and O111 antigens, exist. These VTEC groups did not react with anti-O157
      antibody. Consequently, it is necessary to diagnose the VT gene in these
      bacteria. Therefore, we have designed a sensitive and specific method for the
      detection of two VT genes simultaneously, utilizing duplex PCR with time-resolved
      fluorescence immunoassay (TRFIA).

PMID- 12002597
TI  - Measurement of free radicals and NO by chemiluminescence to identify the
      reperfusion injury in renal transplantation.
AB  - Oxygen free radicals are generated during the reperfusion of ischaemic organs.
      Several experimental studies have demonstrated that the damage produced by
      reperfusion can be prevented by a scavenger of free radicals. Furthermore, a
      significantly improved 5 year graft survival rate after cadaveric renal
      transplantation has been reported in patients treated with scavengers of free
      radicals (Land et al., 1993). Therefore, a question remains to be answered:
      whether a routine monitoring of the radical-mediated reperfusion injury with
      renal transplantation is useful, and whether there is a necessity for a
      generalized protective treatment in transplant patients. In a prospective trial,
      we evaluated a group of eight patients during and after renal cadaveric
      transplantation (three men, five women), using the chemiluminometric measurement
      of serum free radicals and NO. The serum quantities of free radicals and NO were
      significantly increased after reperfusion of the transplant kidney (p < 0.02).
      The mean time of noticeably increased levels of serum free radicals was 4.8 +/-
      1.2 h after reperfusion. The results thus showed an increased liberation of free
      radicals in the peripheral blood of transplant recipients as possible evidence of
      free radicals-mediated reperfusion injury in renal transplantation. The
      generation of free radicals measured by chemiluminescence allow a controlled
      therapy to decrease the generation of free radicals with antioxidants during the
      early transplantation period e.g. in older recipients.

PMID- 12002598
TI  - MR-guided intravascular catheter manipulation: feasibility of both active and
      passive tracking in experimental study and initial clinical applications.
AB  - PURPOSE: To evaluate clinically the feasibility and usefulness of MR-guided
      intravascular procedures with either active or passive tracking. METHODS: With an
      active MR tacking system and a 0.2 Tesla open MR imager, real-time and biplane
      displays of positions of a receive-only coil at the tip of catheters were
      obtained. For passive tracking, 4 Fr catheters with suitable susceptibility for
      passive tracking were used. Passive tracking with a 1.5 Tesla MR imager could be
      performed with parameters of TR 15-50 msec, TE 2.2-2.7 msec, and FA 30 degrees.
      The temperature of each tracking catheter was monitored in vitro. Clinical trials
      were performed on six patients (three each). The catheter was introduced to the
      superior mesenteric artery (SMA) under MR guidance by active or passive tracking
      to perform MR imaging during arterial portography. RESULTS: The temperature
      increased minimally. In humans, the SMA and celiac artery could be easily
      introduced on active tracking. MR-guided manipulation of catheters by active or
      passive tracking in the model and in dogs' vessels was very successful.
      Introduction of the catheter into the SMA was successful in two cases of active
      tracking and in all cases of passive tracking. CONCLUSION: The MR-guided
      intravascular manipulation of catheters by active or passive tracking may be a
      clinically feasible method.

PMID- 12002599
TI  - Extension of breast cancer: comparison of CT and MRI.
AB  - PURPOSE: To compare three-dimensional (3D) helical CT with 3D MRI in the
      evaluation of intraductal spread of breast cancer. METHODS: Fifty patients with
      breast cancer were examined. Tumor size ranged from Tis to T2. The whole breast
      was scanned by both breath-holding helical CT and MRI with contrast media. Linear
      or segmental enhancement, and spotty enhancement around the main tumor were
      considered to indicate ductal carcinoma in situ (DCIS) or ductal spread. These
      findings were compared with thin section histopathologic data. RESULTS: Seventeen
      of 35 patients had intraductal spread with invasive cancer and 15 patients had
      DCIS. The sensitivity, specificity, and accuracy of 3D CT in detecting
      intraductal spread or DCIS were 71.9%, 83.3%, and 76.0%, respectively, and those
      of 3D MRI were 87.5%, 61.1%, and 78.0%. Overestimations numbered three (6.0%) on
      CT and seven (14.0%) on MRI, and underestimations numbered nine (18.0%) on CT and
      four (8.0%) on MRI. CONCLUSION: 3D helical CT can provide good information about
      the spread of breast cancer and could be an alternative to 3D MRI for
      preoperative examination of breast cancer.

PMID- 12002600
TI  - High dose rate endovascular brachytherapy in aorto-iliac lesion for the
      prevention of restenosis.
AB  - This study examined the applicability of endovascular brachytherapy to larger del
      arteries such as the abdominal aorta and iliac artery. Endovascular brachytherapy
      using an Ir-192 HDR source was administered 11 times to nine patients who had
      undergone percutaneous transluminal angioplasty (PTA) between 1995 and 1999. The
      follow-up lasted 13 to 55 months after treatment (median, 24 months). Eight of
      the 11 lesions have been controlled so far. Although one case developed thrombus
      inside the stent five months later, recanalization was achieved by means of
      retreatment. One patient who underwent low-dose irradiation (6 Gy) without stent
      implantation showed restenosis five months after treatment. We used a centering
      catheter that did not block the blood stream for exact centering of the radiation
      source in larger vessels such as the abdominal aorta. Although endovascular
      brachytherapy is a promising and safe procedure, careful follow-up is needed to
      detect untoward reactions such as thrombosis.

PMID- 12002601
TI  - Double cancer, cholangiocellular and hepatocellular carcinomas, in the cirrhotic
      liver.
AB  - A 70-year-old male patient presented with cirrhotic liver caused by hepatitis C
      virus and complicated with hepatocellular carcinoma. The carcinoma was
      effectively treated by transarterial chemoembolization, but cholangiocellular
      carcinoma occurred in a different segment of the liver and rapidly grew and
      metastasized systemically. He died 13 months after the first admission. Double
      cancer of the liver is uncommon, but it must be considered in the differential
      diagnosis of cases of hepatocellular carcinoma associated with chronic hepatitis
      or cirrhosis. Failure to note the occurrence of cholangiocellular carcinoma is
      thought to be a diagnostic pitfall in the follow-up studies of patients with
      hepatocellular carcinoma.

PMID- 12002602
TI  - Primary breast lymphoma successfully treated with combination therapy including
      local radiation therapy: a report of two cases.
AB  - Recently, a combination of local irradiation and chemotherapy has been suggested
      as a standardized treatment for localized lymphoma. However, it has been
      difficult to establish a standard treatment for localized primary breast lymphoma
      simply because of its rarity. We report two cases of primary breast lymphoma
      successfully treated with a combination therapy including local radiation
      therapy. A 46-year-old woman with stage I primary breast lymphoma was irradiated
      with 30 Gy to the involved breast by 4 MV X-rays and 9 Gy to the involved field
      by electron beam after tumorectomy. Then three cycles of CHOP therapy were
      performed. She has been well and has shown no evidence of disease for 58 months.
      A 72-year-old woman with stage II primary breast lymphoma was treated with three
      cycles of CHOP therapy followed by irradiation with 40 Gy per breast by 4 MV X
      rays. She is well and has been disease-free for 49 months. We suggest that a
      combination of local irradiation and short course of chemotherapy can be useful
      in the treatment of primary breast lymphoma.

PMID- 12002603
TI  - Primary ureteral mucosa-associated lymphoid tissue (MALT) lymphoma--pathological
      and radiological findings.
AB  - In this report we describe the pathological and radiological findings in a
      patient with primary ureteral MALT lymphoma. We suggest that it is useful for the
      differential diagnosis of ureter masses that some MALT lymphomas may show a low
      signal intensity on T2-weighted MR images.

PMID- 12002604
TI  - Subphrenic abscess formation following superselective transcatheter
      chemoembolization for hepatocellular carcinoma.
AB  - In order to achieve better results with hepatocellular carcinoma (HCC), repeated
      treatment using transcatheter hepatic arterial chemoembolization (TAE) with or
      without percutaneous ethanol injection (PEI) has been widely performed. A 73-year
      old woman underwent a repeated (second) TAE two months following the primary TAE
      in combination with PEI. Prior to TAE, computed tomography (CT) with angiography
      revealed that the peripheral liver segment adjacent to the HCC was supplied
      exclusively via arterial flow without portal circulation. Following TAE, she
      developed an extrahepatic abscess with clinical and radiological evidence of
      ruptured HCC. A high-grade fever and right hypochondrial pain were sustained by
      day 10 after TAE, and CT showed a low-density mass extending into the subphrenic
      fluid collection. One hundred milliliters of infected fluid was drained by
      ultrasound-guided percutaneous aspiration from the collection. Following
      drainage, her clinical course was uneventful. Extrahepatic abscess formation is a
      rare complication of TAE, and, to our knowledge, only three cases of subphrenic
      abscess have been reported in the English literature. Severe ischemic necrosis of
      the arterial-feeding liver tissues devascularized by repeated TAE was considered
      to be a major contributor to this clinical condition. Early clinical suspicion
      combined with surgical management is mandatory in preventing serious morbidity of
      peritonitis accompanying repeated TAE.

PMID- 12002605
TI  - Two cases of adrenal hemangioma: CT and MRI findings with pathological
      correlations.
AB  - We present two cases of adrenal hemangioma, a rare non-functioning adrenal tumor,
      and correlate the CT and MR imaging findings with the pathological findings.
      Peripheral spotty contrast enhancement with centripetal enhancement was noted in
      one case. This pattern of enhancement is crucial for diagnosing adrenal
      hemangioma. The other case showed only thin rim enhancement without centripetal
      enhancement. This finding can be seen in other adrenal tumors, making diagnosis
      difficult. Marked hyperintensity on T2-weighted images and focal hyperintensity
      on T1-weighted images that showed focal hemorrhage and calcification were noted.
      These findings can also be seen in other adrenal tumors and are not pathognomonic
      of adrenal hemangioma. However, observing the combination of these findings can
      lead to the correct diagnosis.

PMID- 12002606
TI  - Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on
      computed tomographic imaging.
AB  - PURPOSE: Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the
      thyroid gland are rare malignant tumors, and the initial symptoms of these
      diseases are very similar. The aim of our study was to compare the
      characteristics of the two diseases using computed tomographic (CT) scans in
      order to make an accurate differential diagnosis. MATERIALS AND METHODS: Ten
      patients with LY and 10 with AC were analyzed. Differences in the CT findings of
      the two diseases were evaluated before treatment and statistically tested with
      either Student's t-test or the chi-square test. RESULTS: In the analysis of
      characteristics of CT imaging, the existence of calcification and necrosis, and
      heterogeneous tumor were dominant findings in AC, and there was a statistically
      significant difference in frequency between the two diseases (p < 0.01).
      Calcification detected in AC was usually multiple and/or gross (mean size: phi8.2
      mm). All lymphadenopathies were delineated as having the same homogeneous
      attenuation as the tumors in the thyroid gland in LY, but were shown as irregular
      rim enhancement in AC. CONCLUSION: The CT features of the two diseases are
      characteristic in terms of calcification, necrosis, and tumor composition.
      Evaluation by means of CT imaging is useful in distinguishing between LY and AC.

PMID- 12002607
TI  - The interstitial cells of Cajal and a gastroenteric pacemaker system.
AB  - In spite of a claim by Kobayashi (1990) that they do not correspond to the cells
      originally depicted by CAJAL, a particular category of fibroblast-like cells have
      been identified in the gut by electron microscopy (Faussone-Pellegrini, 1977;
      Thuneberg, 1980) and by immunohistochemistry for Kit protein (Maeda et al., 1992)
      under the term of the "interstitial cells of Cajal (ICC)". Generating electrical
      slow waves, the ICC are intercalated between the intramural neurons and the
      effector smooth muscular cells, to form a gastroenteric pacemaker system. ICC at
      the level of the myenteric plexus (IC-MY) are multipolar cells forming a
      reticular network. The network of IC-MY which is believed to be the origin of
      electrical slow waves is morphologically independent from but associated with the
      myenteric plexus. On the other hand, intramuscular ICC (IC-IM) usually have
      spindle-shaped contours arranged in parallel with the bulk smooth muscle cells.
      Associated with nerve bundles and blood vessels, the IC-IM possess receptors for
      neurotransmitters and such circulating hormones as cholecystokinin, suggesting
      their roles in neuromuscular and hormone-muscular transmissions. In addition, gap
      junctions connect the IC-MY and IC-IM, thereby realizing the electrically
      synchronized integrity of ICC as a pacemaker system in the gut. The smooth muscle
      cells are also coupled with ICC via gap junctions, and the functional unit thus
      formed enables rhythmically synchronized contractions and relaxations. It has
      recently been found that a lack of Kit-expressing cells may induce hyper
      contractility of the tunica muscularis in vitro, whereas a decrease in Kit
      expression within the muscle wall causes dysmotility-like symptoms in vivo. The
      pacemaker system in the gut thus seems to play a critical role in the maintenance
      of both moderate and normal motility of the digestive tract. A loss of Kit
      positive cells has been detected in several diseases with an impaired motor
      activity, including diabetic gastroenteropathy. Pathogenesis of these diseases is
      thought to be accounted for by impaired slow waves and neuromuscular
      transmissions; a pacemaker disorder may possibly induce a dysmotility-like
      symptom called 'gastroenteric arrhythmia'. A knowledge of the structure and
      function of the ICC and the pacemaker system provides a basis for clarifying the
      normal mechanism and the pathophysiology of motility in the digestive tract.

PMID- 12002608
TI  - Cellular localization of the diazepam binding inhibitor in glial cells with
      special reference to its coexistence with brain-type fatty acid binding protein.
AB  - The diazepam binding inhibitor (DBI) was originally isolated from the brain as an
      intrinsic ligand of the benzodiazepine binding site on the type-A gamma
      aminobutyric acid receptor (GABA(A) receptor). Its wide-spread distribution in
      non-neural tissues outside the brain suggests that DBI has various functions
      other than GABA-mediated neurotransmission. Since DBI is identical with the acyl
      CoA binding protein, which has the ability to bind long chain acyl-CoA esters,
      the major function of DBI may possibly be related to lipid metabolism. This idea
      was supported by our previous study showing the consistent coexpression of DBI
      and fatty acid binding proteins (FABPs) in epithelia throughout the
      gastrointestinal tract. The present histochemical study focused on the
      distribution of DBI in neural tissues, and revealed a definite existence of DBI
      in non-neuronal supporting cells in both the central and peripheral nervous
      systems. In the brain, intense immunoreactivity for DBI was detected in the
      cerebellar Bergmann glia, olfactory ensheathing glia, subgranular layer of the
      dentate gyrus, and retinal Muller cells. In the peripheral nervous system,
      satellite cells in sensory/autonomic ganglia, Schwann cells, and sustentacular
      cells in the adrenal medulla were immunoreactive to a DBI antibody. Moreover, the
      colocalization of DPI and brain-type FABP (B-FABP) was observed in most of the
      non-neuronal supporting cells mentioned above, indicating that DBI and B-FABP are
      cooperatively involved in the energy metabolism of astrocytes and related cells,
      which are thought to support neuronal development and functions.

PMID- 12002609
TI  - Structural aspects of the extracellular matrix of the tendon: an atomic force and
      scanning electron microscopy study.
AB  - The mutual interactions of small proteoglycans with collagen fibrils in the
      extracellular matrix remain to be completely understood. The present research
      investigated the extracellular matrix of the rat tail tendon by atomic force
      microscopy (AFM) as well as by scanning electron microscopy (SEM). Observations
      showed simply dehydrated specimens made of large heterogeneous fibrils, tightly
      packed in mutual contact with no visible interfibrillar spaces. Proteoglycans
      usually extended onto neighboring fibrils, forming an intricate interfibrillar
      weaving highly sensitive to chondroitinase digestion. Pre-treatment with
      cupromeronic blue only affected the proteoglycans side chains, which appeared
      better preserved but somewhat thickened. Observation of hydrated specimens by AFM
      confirmed the close packing of collagen fibrils and the abundance of collagen
      bound proteoglycans. Interfibrillar bridges were only occasionally observed in
      this tissue, whose fibrils are instead tightly bound together by proteoglycans in
      a structure quite consistent with its functional requirements. The molecular
      machinery responsible for these interactions is the subject of ongoing research.

PMID- 12002610
TI  - Effects of postnatally administered inorganic lead on the tyrosine hydroxylase
      immunoreactive norepinephrinergic neurons of the locus ceruleus of the rat.
AB  - The neurotoxic effects of inorganic lead are known to include peripheral
      neuropathy in adults and encephalopathy in children. The purpose of this study
      was to determine the effect of inorganic lead (PbCl2) administration on
      norepinephrinergic neurons of the locus ceruleus in neonatal rats by
      immunocytochemical and electron microscopic analyses. Lead chloride solutions,
      0.05%, 0.1% and 0.2% in concentrations, were prepared in distilled water and
      administered orally via drinking water. After 4, 8, or 12 weeks of continuous
      administration, the rats were sacrificed and brains were immunostained with the
      tyrosine hydroxylase antibody. The number of immunoreactive cell bodies in the
      locus ceruleus was estimated. Densitometric analysis of immunoreactive profiles
      visualized by electron microscopy was performed using an image analyzer. The
      numbers of immunoreactive neurons in the locus ceruleus were increased
      statistically by lead administration. The intensity of the immunoreaction, both
      under the light and electron microscopes was also increased. Degenerative
      changes, including intra-axonal vacuole formation and widening of the
      extracellular spaces, were found by electron microscopy in and around the
      tyrosine hydroxylase immunoreactive axons. Increased tyrosine hydroxylase
      immunoreactivity may correlate with the hyper-reactivity of lead intoxicated
      children. Degenerative changes may account for the reported deficits in
      intellectual attainment and achievement in lead intoxicated children.

PMID- 12002611
TI  - Developmental changes in the structure of the rat fetal lung, with special
      reference to the airway smooth muscle and vasculature.
AB  - Structural changes in the developing rat lung were studied by a combined use of
      light microscopy including immunohistochemistry for a-smooth muscle actin (alpha
      SMA) and scanning electron microscopy (SEM) using the KOH-collagenase digestion
      method. In the embryonic stage (E11-E13), the lung bud appeared as an outgrowth
      from the ventral wall of the foregut which grew caudally into the splanchnic
      mesoderm to form a pair of bronchial buds at the end. At E13, the airway smooth
      muscle cells first appeared around the bifurcation of the trachea. These smooth
      muscle cells were restricted to the dorsal surface of the tracheal epithelium,
      suggesting a difference in character between the dorsal and ventral sides of the
      mesenchymal cells in this region. During the pseudoglandular stage (E13-E18.5),
      the bronchial buds repeatedly gave off branches in the mesenchymal tissue. The
      smooth muscle cells in the bronchioles were spindle-shaped and arranged
      completely circularly around the epithelial tube, except that the terminal bud of
      bronchioles lacked the smooth muscles. The neck of the terminal bud was
      constantly surrounded by flat and irregularly-shaped immature smooth muscle
      cells, representing an early event in the smooth muscle cell differentiation from
      mesenchymal cells. In the canalicular to saccular stages (E18.5 to birth), the
      terminals of bronchioles became saccular, thus forming prospective alveolar
      acini. At birth, the alveolar wall became thinner than before birth, and the
      individual smooth muscle cells in bronchioles were elongated like a tape. As to
      the blood vessel differentiation, various sized sinusoidal spaces indicating the
      primitive blood vessels were already present in the mesenchymal tissue at E11.5.
      The endothelial cells of these sinusoidal spaces were irregularly shaped and
      sometimes extended their processes into the lumen. The network of tubular vessels
      appeared from E14.5. These vessels had tapering ends as well as transluminal
      trabeculae, suggesting that capillary growth proceeds by both the sprouting and
      partitioning (i.e., intussusception) of vessels in the pseudoglandular stage.

PMID- 12002612
TI  - Fine structure of the mouse portal vein in relation to its peristaltic movement.
AB  - The hepatic portal vein has been known to make a spontaneous peristaltic movement
      in some mammals, including the mouse and rat. To investigate the fine structure
      of the portal vein in relation to its physiological characteristics, we observed
      the mouse portal vein by using various histological techniques including
      conventional light microscopy, videomicroscopy, transmission and scanning
      electron microscopy, and real-time confocal laser scanning microscopy. The mouse
      hepatic portal vein was provided with a spiral fold which was produced by the
      inner layer, i.e. the endothelium and smooth muscles of the wall protruding into
      the lumen. Longitudinal smooth muscle cells spanned the interval of the fold,
      like a spirally arranged palisade around the vessel wall. The longitudinal muscle
      fibers ended at the spiral fold, being partly connected with a network of
      irregularly shaped smooth muscle cells. This network, hitherto unknown, was
      recognized to be restricted to the fold in distribution and characterized by
      numerous gap junctions connecting the muscle cells. Real-time confocal laser
      scanning microscopy using a Ca2+ sensitive fluorescent dye revealed that a
      transient and periodic increase in Ca2+ concentration occurred in the
      longitudinal smooth muscle cells and was transmitted spirally from the intestinal
      to the hepatic side. These findings indicate that, during the peristaltic
      movement, the contraction of smooth muscle cells is transmitted along the
      longitudinal smooth muscles of the portal vein wall toward the liver, presumably
      controlled by the network of the irregularly-shaped smooth muscle cells in the
      fold of the portal vein. Light microscopic observation in some specimens
      indicated an occurrence of cardiac muscle cells outside the smooth muscle layer.
      Restricted to the site of the porta hepatis in distribution, their involvement in
      the peristaltic contraction of the portal vein seemed unlikely.

PMID- 12002613
TI  - Localization and expression of the aquaporin-1 water channel in mesangial cells
      in the human glomerulus.
AB  - The expression and localization of the aquaporin-1 (AQP1) water channel were
      examined in the glomeruli of the human kidney. A ribonuclease protection assay
      showed the expression of AQP1 mRNA in human glomeruli but not in rat glomeruli.
      Western blot analysis revealed 28 kDa and 35 kDa bands corresponding to
      unglycosylated and glycosylated AQP1 proteins in human glomeruli. Immunoreactive
      AQP1 was demonstrated almost exclusively in the mesangium in the human glomeruli
      by immunohistochemistry. The endothelium of glomerular capillaries was only
      partly immunostained while podocytes and Bowman's capsule epithelia were not
      immunolabeled. Immunoelectron microscopy localized the immunoreactive AQP1 on the
      plasma membrane of mesangial cells in human glomeruli. The immouno-gold labeling
      was dense on the projections of mesangial cells protruding to the glomerular
      capillary lumen or to endothelial cells, but was sparse on other parts of the
      mesangial cell surface. No immunoreactivity for AQP1 was demonstrated in rat
      glomeruli. This study showed the distinct localization of AQP1 in the mesangial
      cells of human glomeruli, suggesting its role in water movement through these
      cells.

PMID- 12002614
TI  - Expression of the metabotropic glutamate receptor, mGluR4a, in the taste hairs of
      taste buds in rat gustatory papillae.
AB  - Taste-mGluR4, cloned from taste tissues, is a truncated variant of brain
      expressed mGluR4a (brain-mGluR4), and is known to be a candidate for the receptor
      involved in the umami taste sense. Although the expression patterns of taste- and
      brain-mGluR4 mRNAs have been demonstrated, no mention has so far been made of the
      expression of these two mGluR4 proteins in taste tissues. The present study
      examined the expression of taste-mGluR4 and brain-mGluR4 proteins in rat taste
      tissues by using a specific antibody for mGluR4a which shared a C-terminus of
      both taste- and brain-mGluR4, for immunoblot analysis and immunohistochemistry.
      Immunoblot analysis showed that both brain-mGluR4 and taste-mGluR4 were expressed
      in the taste tissues. Taste-mGluR4 was not detected in the cerebellum. The
      immunoreactive band for brain-mGluR4 protein was much stronger than that for
      taste-mGluR4 protein. In the cryosections of fungiform, foliate and circumvallate
      papillae, the antibody against taste-mGluR4 exhibited intense labeling of the
      taste pores and taste hairs in all the taste buds of gustatory papillae examined;
      the immunoreaction to the antibody against brain-mGluR4 was more intense at the
      same sites of the taste buds. The portions of the taste bud cells below the taste
      pore and surrounding keratinocytes did not show any immunoreactivities. The
      results of the present study strongly suggest that, in addition to taste-mGluR4,
      brain-mGluR4 may function even more importantly than the former as a receptor for
      glutamate, i.e. the umami taste sensation.

PMID- 12002615
TI  - Developmental study of the anal tonsil in the laboratory shrew, Suncus murinus.
AB  - The laboratory shrew, Suncus murinus, which lacks such gut associated lymph
      organs as the appendix and Peyer's plates, was recently demonstrated (Kubo and
      Isomura, 1996) to possess a pair of anal tonsils at the end of its rectum. The
      present paper deals with the development of this lymphoid organ as observed by
      light and electron microscopy. The anal tonsil was characterized by the initial
      postnatal development. On neonatal Day 1, a pair of epithelial crypts formed at
      the dorsal boundary between the anus and the ostium urogenitoanale. On Day 2
      after birth, lymphocytes began to accumulate in the subepithelial mesenchymal
      tissue under the crypt. From Day 3 on, the lymphocytes increased to form a lymph
      nodule, from which, on Day 5, some lymphocytes began to penetrate into the crypt
      epithelium. The crypt and the nodule were fused together between Days 6 and 8. A
      germinal center-like structure was observed on Day 20 after birth. Around Day 40,
      the invading cells comprised cellular units consisting of large and small
      lymphocytes and plasma cells. High endothelial venules were observed in the
      parafollicular area at this time. These findings indicate that the anal tonsil
      originates from an accumulation of lymphocytes in the mesenchymal tissue close to
      a particular epithelium of the crypt, presumably in response to antigens in
      foods; the tonsilar structure is then gradually completed by fusion of the
      lymphoid and epithelial elements. This paper further reports on an electron
      microscope finding on Day 8 where the anal tonsillar crypt epithelium was seen to
      contain some basal-granulated cells of the open type.

PMID- 12002616
TI  - Quantitative method of intracellular hepatitis C virus RNA using LightCycler PCR.
AB  - Based on recent LightCycler techniques developed for the quantitation of serum
      HCV RNA, we have developed a quantitative method for the intracellular hepatitis
      C virus (HCV) RNA using LightCycler PCR. A simple real-time PCR assay, based on
      the SYBR Green I dye and LightCycler fluorimeter and with no probe requirement,
      is described. In the presence of 0.5 microg of cellular RNA, it was demonstrated
      that as few as 25 copies of HCV RNA could be specifically detected with a set of
      primers that amplify a 144-base pair sequence unique to the 5'-noncoding region
      of HCV RNA. We demonstrated that this method was useful for the evaluation of
      antiviral reagents using HCV-infected human cultured cells.

PMID- 12002617
TI  - A study on intraalveolar exudates in acute mycoplasma pneumoniae infection.
AB  - Pathologic features of Mycoplasma pneumoniae infection (M. pneumonia) are
      generally non-specific, and the literature regarding the pathologic features of
      M. pneumonia with intraalveolar exudates is limited. Clinical and
      histopathological studies were performed in 3 patients with M. pneumonia which
      did not respond to erythromycin and minocycline, but all rapidly recovered after
      corticosteroid therapy. In pathologic findings, we observed intraalveolar
      exudates and focal organization in M. pneumonia, and its intraalveolar lesions
      were compared between M. pneumonia and bronchiolitis obliterans organizing
      pneumonia containing fibrin (BOOP). Immunohistochemical studies were performed
      using the streptavidin biotin peroxidase complex method with anti-alpha-smooth
      muscle actin antibody and anti-pancytokeratin AE1/AE3 antibody. In pathologic
      findings, more fibrin deposits in intaalveolar lesions were observed in M.
      pneumonia than in BOOP. In intaalveolar lesions of M. pneumonia, a larger amount
      of nuclear debris, more neutrophils, and more erythrocytes were noted.
      Myofibroblasts were observed in the organization of BOOP, while in the
      intaalveolar lesions of M. pneumonia, myofibroblasts were not observed. These
      results suggest that M. pneumonia with intraalveolar exudates responds well to
      corticosteroid and its intraalveolar lesions apparently differed from those in
      BOOP.

PMID- 12002618
TI  - Intraluminal implantation of rectal carcinoma successfully resected by endoscopy.
AB  - A 55-year-old Japanese woman presented at our hospital complaining of
      hematochezia 4 months after surgery for a rectal carcinoma. A proctoscopy
      revealed 2 protuberant lesions in the rectum, 5 mm anally from the anastomotic
      suture line. The diagnosis of adenocarcinoma was confirmed by biopsy. It was
      considered that these lesions were caused by intraluminal implantation from the
      primary rectal carcinoma. The patient underwent an endoscopic resection for these
      recurrent lesions and has remained stable, with neither recurrence nor
      metastasis, in the 7 years since the resection. For rectal carcinoma, we propose
      early follow-up by proctoscopy, namely within 4 months after surgery.

PMID- 12002619
TI  - Molecular biology and genetics of epilepsy.
AB  - Genetic and molecular biological methodologies are being applied to the study of
      patients with epilepsy at an ever-increasing pace. Accurate classification of
      epilepsy within large families has allowed identification of genes through
      linkage analysis and then isolation of gene products. Mutations causing ion
      channel abnormalities coupled with clinical patterns of focal epilepsy syndromes
      are beginning to change our thinking about the etiology of recurrent seizures in
      all patients. Molecular methodology is beginning to have impact on understanding
      of the mechanisms of actions of drugs used to treat epilepsy and will have an
      impact on how future treatments are designed.

PMID- 12002620
TI  - Experimental models of small intestinal transplantation in rats: orthotopic
      versus heterotopic model.
AB  - Two kinds of surgical models of small intestinal transplantation (SITx) in rats,
      namely heterotopic (HIT) and orthotopic transplantion (OIT), have been reviewed.
      In OIT, the small intestine of the recipient is removed and the transplanted
      intestine replaces it in continuity. On the other hand, in the HIT model, the
      small intestinal grafts are rendered dysfunctional without alimentary tract
      continuity. Histological evidence showed that acute rejection appeared earlier in
      HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa
      produced in the chronic rejection process were more pronounced in HIT allografts.
      The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal
      trophic factors, because oral feedings can stimulate tropic hormones for mucosal
      growth, and provide nutrients for enterocytes. Intestinal permeability was
      consistently higher after HIT than after OIT. The HIT grafts demonstrated less
      contractility and less response to chemical stimulation than did OIT grafts. The
      OIT models are advantageous in studies of intraluminal nutrients, and intestinal
      secretions in these models might modulate the intestinal immune status and
      possibly delay rejection. The superior intestinal barrier function and the
      delayed onset of rejection in OIT rats suggest that nutrients and other factors
      in the succus entericus are important for the maintenance of intestinal graft
      function.

PMID- 12002621
TI  - Kinesiological study of the push-up motion in spinal cord injury patients:
      involving measurement of hand pressure applied to a force plate.
AB  - We studied the pressure exerted by hands during push-ups in 21 paraplegic and 2
      tetraplegic patients employing 4 different hand positions. In the fingers-spread
      position, the initial force exerted was a vertical force (Fz), followed by a
      medio-lateral force (Fy) and then an antero-posterior force (Fx). In the other 3
      positions, the order of force type exertion was Fz, Fx, and then Fy. All subjects
      with neurological injury levels above T4 and subjects between T5 and T10 without
      spinal instrumentation could not push themselves up in the fingers-spread
      position. The fact that Fy is initiated before Fx in the fingers-spread position
      indicates that lateral balancing of the trunk is critical in this position, thus
      explaining why subjects without spinal instrumentation with neurological injury
      at a level higher than T10 could not control their spinal columns while
      performing push-ups. In contrast, antero-posterior balancing takes priority in
      the other hand positions. We believe that spinal instrumentation helps balance
      the trunk in the lateral direction, converting the thoracic spine into a rigid
      body in subjects with neurological injury at levels above T10.

PMID- 12002622
TI  - The distribution and number of Leu-7 (CD57) positive cells in lung tissue from
      patients with pulmonary fibrosis.
AB  - Leu-7 positive lymphocytes, including natural killer cells, play an important
      role in the immune system's surveillance function to prevent the development of
      cancer. The incidence of lung cancer is significantly high in patients with end
      stage pulmonary fibrosis. We hypothesized that the number of Leu-7 positive cells
      may be decreased in areas of severe pulmonary fibrosis. To demonstrate this, Leu
      7 positive cells were immunohistochemically stained in 41 lung specimens obtained
      from patients with idiopathic pulmonary fibrosis and pulmonary fibrosis
      associated with collagen vascular disorders. The number of Leu-7 positive cells
      was evaluated according to the pathological findings. In pathologically normal
      lung, Leu-7 positive cells were mostly found within the capillaries of the septa
      and rarely in the alveolar space or the stroma. The number of Leu-7 positive
      cells was 0.69 +/- 0.15 in areas of advanced fibrosis (n = 41), 2.39 +/- 0.60 in
      areas that had newly developeing fibrosis (n = 41), 1.14 +/- 0.57 in
      bronchiolitis obliterans organizing pneumonia (n = 9), and 1.35 +/- 0.87 in
      diffuse alveolar damage (DAD) (n = 11). The number of Leu-7 positive cells in
      areas of newly developing fibrosis (2.39 +/- 0.60) was significantly higher than
      that in areas of established fibrosis (0.69 +/- 0.15, P < 0.05). Our present
      study demonstrates a significant decrease in the number of Leu-7 positive cells
      in areas of advanced fibrosis. This evidence may partly explain the high
      incidence of lung cancer associated with pulmonary fibrosis.

PMID- 12002623
TI  - Role of the limbus in femoral-head deformation in developmental dislocation of
      the hip: findings of two-directional hip arthrography.
AB  - Two-directional arthrographic findings made during conservative treatment of
      developmental dislocation of the hip were compared with the femoral-head
      configurations and radiological results obtained from long-term follow-up
      examinations in this retrospective study. Sixty hips were followed until at least
      age 14. Arthrography was carried out according to Terazawa's method. The shape of
      the superior, anterior, and posterior limbus was evaluated based on a modified
      Fujii's classification. The femoral-head configuration was classified into 4
      groups, and the radiological results were evaluated using Severin's
      classification at the final observation. There was a statistically significant
      relationship between the shape of the anterior limbus, the number of portions of
      deformed limbus (superior, anterior, posterior), and the femoral-head
      configuration. Also, a statistically significant relationship between the shape
      of the limbus and Severin's classification was observed. These results suggest
      that the deformed limbus seems to play an important role in triggering femoral
      head deformities, possibly via mechanical compression, and negatively affects
      development of the hip joint.

PMID- 12002624
TI  - Anti-asialoglycoprotein receptor autoantibodies, detected by a capture
      immunoassay, are associated with autoimmune liver diseases.
AB  - In autoimmune chronic active hepatitis (AIH) and primary biliary cirrhosis (PBC),
      various autoantibodies including anti-asialoglycoprotein receptor (ASGPR)
      antibodies have been found in patients' sera. We have previously developed a
      mouse monoclonal antibody against rat and human ASGPR. In this study, we
      developed a capture enzyme-linked immunosorbent assay (ELISA) for detection of
      anti-ASGPR antibodies using this monoclonal antibody and investigated the
      occurrence of anti-ASGPR antibodies in the sera of patients with various liver
      diseases. Serum samples were obtained from 123 patients with various liver
      diseases, including 21 patients with AIH and 40 patients with PBC. In this
      capture ELISA, the target antigen in the crude rat liver membrane extracts was
      captured on the ELISA wells by the ASGPR-specific mouse monoclonal antibody.
      Thus, the cumbersome process of antigen purification was rendered unnecessary.
      Using this capture ELISA, we detected the anti-ASGPR antibody in 67% of the
      patients with AIH, in 100% of the patients with PBC, and in 57% of the patients
      with acute hepatitis type A. However, the anti-ASGPR antibody was rarely detected
      in patients with other liver diseases such as primary sclerosing cholangitis and
      obstructive jaundice. Our findings suggest that this capture ELISA would be
      useful for the detection of anti-ASGPR antibodies in autoimmune liver diseases.

PMID- 12002625
TI  - The everyday realities of the multi-dimensional role of the high school community
      nurse.
AB  - The traditional role of the high school based community community health nurse
      has changed considerably over recent decades. This article describes a
      qualitative study, in which nine community health nurses from eight different
      high schools completed a diary of the interventions and events during the course
      of two working days in order to identify the dimensions of their role. A short
      demographic questionnaire was also completed by the nurses and included two open
      ended questions concerning their main professional issues and concerns. The
      researchers sought verification of the interpretation of the data through a focus
      group interview with the high school nurses. Data analysis indicated that the
      role of the high school community health nurses (CHN) consisted of seven
      categories. These were provider of clinical care, counsellor/ mediator, advocacy
      and support, liaison/referral, health promotion/education and resource agent, and
      professional management and research role. The findings highlight the complex and
      demanding aspects of the role of the high school nurse and articulate the
      importance of describing the contribution of such practitioners in to the
      promotion of health among adolescents.

PMID- 12002626
TI  - Living with loss: dementia and the family caregiver.
AB  - Two focus group interviews with 15 relatives, investigated family caregivers'
      perceptions of having a relative in a dementia care unit. Data analysis revealed
      the significant theme of living with loss. The results demonstrate that the
      burden of care giving creates growing stress and tension that continues even when
      the family member is placed into a residential care setting. The findings suggest
      that health professionals must be prepared to assist family members with the
      anticipatory grieving of losses that accrue with the changing relationship with
      the relative and health care staff. Furthermore, there is a need to look for a
      means of helping and supporting family caregivers so that they can develop a
      sense of satisfaction and accomplishment in their care giving role.

PMID- 12002627
TI  - Pregnant women's experiences of models of care in some hospitals in Victoria.
AB  - During the data analysis of a much larger study on 13 women's experiences of
      their first pregnancy, their interactions with the health system emerged as
      significant. Two grounded theory procedures, the making of comparisons and the
      asking of questions were used to analyse their experiences. Elements of three
      models of care were identified, medical/technocratic model, midwifery model, and
      a feminist perspective model. In some instances, there was blurring and
      overlapping of models. Tape-recorded, individual interviews were held with 13
      pregnant women (aged 34-42 years) in their homes at the end of each trimester and
      with 10 women again 10-14 days post birth. (Three women were unavailable.) All
      the women delivered their babies in hospital. Eleven women had an epidural
      anaesthetic and 11 women had an episiotomy. Information received at antenatal
      education classes had a marked effect on the women's expectations and the reality
      of their experiences. The future of implementing midwifery models of care into
      the hospital system will depend on effective change management and an
      acknowledgment of consumer needs by administrators.

PMID- 12002628
TI  - The experience of seeking help for postnatal depression.
AB  - This qualitative study sought to explore women's experiences of support and
      treatment for postnatal depression. In-depth interviews from seven women were
      analysed using the phenomenological method described by Creswell (1998). Findings
      indicate that partners provided women the most support. The women did not know
      where to seek professional help, often being identified and helped by the
      maternal health nurse who monitors and guides the progress of their babies'
      development. Hospital programs were criticised for not informing and involving
      family. The women were dissatisfied with hospital doctors and their GPs claiming
      they had limited time for counselling, preferring to prescribe medication that
      alleviated symptoms but reinforced feelings of inadequacy. Recommendations are
      made to involve families and to use the unique position of the maternal health
      nurse in assessing new mothers.

PMID- 12002629
TI  - Reflections on nursing.

PMID- 12002630
TI  - Queensland public sector nurse executives: professional development needs.
AB  - In a time of health care reform and rapid change, nurse executives need effective
      leadership skills to be able to respond to a challenging environment, provide
      quality cost-effective care and promote the professional development of nursing.
      This research aimed to provide an understanding of nursing executives' roles and
      professional development needs and obtain concise information for the development
      of strategies and professional development programs to enhance the effectiveness
      of the present and future roles of nursing executives. A descriptive cross
      sectional postal survey was sent to all public sector Level 4 and 5 nursing
      executives in Queensland (n = 281), with a response rate of 52.3% (n = 147).
      Financial management, human resource management and information technologies were
      identified as the areas where professional development was most needed.
      Structured educational activities such as short courses or seminars covering
      information technology, financial and budget management and general business
      management were identified as the type of activities best suited to nurse
      executives' needs. The most frequently reported barriers to professional
      development were difficulties obtaining relief staff, inadequate time, financial
      cost and inadequate district manager and regional support to enable access to
      professional development programs.

PMID- 12002631
TI  - The use of information and communication technology in veterinary education.
AB  - The internet provides new opportunities to deliver distance and e-learning to the
      veterinary profession both at undergraduate and postgraduate levels. There are
      now numerous examples of successful computer-based educational projects in UK
      higher education, which provide useful models for veterinary science. This will
      present challenges for academics who will need to adapt their teaching
      methodologies and students who will have to develop new ways of learning. The
      future of Information and Communication Technologies (ICT) in the veterinary
      sector is difficult to predict but it is likely to have far reaching effects on
      the profession.

PMID- 12002632
TI  - Plasma disposition, faecal excretion and in vitro metabolism of oxibendazole
      following oral administration in horses.
AB  - Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(
      1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and
      1.0 hours post administration sampling times and the mean maximum plasma
      concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between
      12 and 72 hours after administration and the highest dry faecal concentration was
      detected at 24 hours. An unidentified metabolite was detected in plasma between
      0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses
      corresponded to the second eluted metabolite in the in vitro study. Metabolism of
      OBZ to its metabolite in vitro was significantly inhibited by co-incubation with
      the cytochrome P450 inhibitor piperonyl butoxide. These results indicated that
      first-pass metabolism decreases OBZ bioavailability in horses. The in vitro
      metabolism of OBZ was significantly inhibited by piperonyl butoxide and this
      could be utilised to extend the exposure of nematodes to the parent molecule.

PMID- 12002633
TI  - Concentrations of triiodothyronine (T3), tumour necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) in milk from healthy and naturally infected quarters of
      cows.
AB  - The effect of naturally acquired bacterial infection of the bovine udder on the
      activity of 5'-thyroxine monodeiodinase (5'-MD), and on the concentrations of the
      pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)
      alpha in milk, from healthy (control) and inflamed quarters, was determined. The
      diagnostic procedure included history and clinical examination of the udder,
      macroscopic evaluation of secretions, the Californian Mastitis Test,
      determination of somatic cell counts and bacteriological examination of milk. It
      has been found that the milk triiodothyronine (T3) content and the 5'-MD activity
      from inflamed quarters were decreased when compared with controls. The decrease
      in the milk T3 from subclinical mastitic quarters was manifested when somatic
      cell counts were > 10(6) ml(-1). TNF-alpha was on average 2-fold higher in
      infected milk, and the concentration of IL-6 was unchanged. These results suggest
      that the decreased T3 content in mammary secretions during naturally occurring
      mastitis is associated with the severity of inflammation, increased TNF-alpha
      concentration and impaired enzymatic activity of 5'-MD.

PMID- 12002634
TI  - Some aspects of erythrocyte metabolism in insulin-treated diabetic dogs.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a common metabolic disease often
      complicated by a number of pathological conditions among which are haematological
      changes and alterations in blood cell function. Human and feline diabetes
      mellitus patients have been reported to be associated with oxidative stress that
      can lead to membrane alterations and to reduced erythrocyte life-span.
      Erythrocyte function in dogs affected by IDDM has been investigated during
      insulin therapy, paying attention to antioxidant status, membrane resistance,
      enzyme activities and 2,3-diphosphoglycerate (2,3DPG) concentration. Thirteen
      diabetic and 36 healthy dogs were bled and haematology and blood chemistry assays
      were performed to evaluate the degree of compensation. Osmotic fragility, the
      activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and pyruvate
      kinase (PK) and the concentrations of reduced glutathione (GSH) and 2,3DPG were
      evaluated in the erythrocytes. Diabetic dogs did not differ from controls in
      terms of haematological parameters, except for higher numbers of platelets.
      Higher values of fructosamine, glucose, protein, plasma potassium and calculated
      osmolality were detected in the plasma from diabetic dogs. No differences were
      detected in osmotic fragility, GSH concentration and PK activity between the two
      groups but 2,3DPG concentration and G6PD activity were statistically
      significantly higher in the diabetic group. The results indicate minimal
      alterations in erythrocyte functions occur in insulin-treated diabetic dogs. This
      contrasts with what has been reported for IDDM humans and cats.

PMID- 12002635
TI  - The effects of aflatoxin on the reproductive system of roosters.
AB  - This study was conducted to determine the pathological changes in testes and
      epididymides and plasma testosterone levels of adult roosters during
      experimentally induced aflatoxicosis. In the study, 24 months of age, 32 Babcock
      breeder males were used, and they were divided into four groups each containing 8
      animals. The groups were designed as follows; group 1: Control, no aflatoxin
      (AF), group 2: 5 ppm (parts per million) total aflatoxin (AF; B1, B2, G1, G2),
      group 3: 10 ppm AF and group 4: 20 ppm AF in the diet, and the birds were fed for
      8 weeks. Grossly, it was seen that the testes of all AF-treatment groups birds
      were significantly (P < 0.001) atrophied when compared with those of control
      birds. Histopathologically, there was no spermatogenesis in the testes of 4, 5
      and 6 cocks fed on a diet containing AF 5, 10 and 20 ppm, respectively.
      Furthermore, abnormal spermatozoa were observed in some of AF-treatment groups
      (in 2 cases in each of 5 and 10 ppm AF-treated groups, and in one case in 20 ppm
      AF-treated group). There were also mononuclear cell infiltration and/or focal
      lymphoid cell accumulation in the intertubular areas of the testes and
      epididymides in all AF-treatment groups. In conclusion, it has been shown that AF
      might totally or partially (dose related) suppress spermatogenesis, cause
      abnormality in spermatozoa and atrophy in testes. Furthermore, there was
      degeneration and desquamation in the epithelium and decrease in the size and
      thickness of the germinative layer of the seminiferous tubules, and lowered
      plasma testosterone levels in adult roosters.

PMID- 12002636
TI  - Evaluation of the effects of controlled autolysis on the immunodetection of
      PrP(Sc) by immunoblotting and immunohistochemistry from natural cases of scrapie
      and BSE.
AB  - Seventeen clinically suspect scrapie sheep, and twelve suspected BSE-affected
      cattle were confirmed using routine histopathological examination by the
      detection of characteristic spongiform change in the medulla brain region taken
      at the level of the obex. Three sheep and four cows acquired as controls showed
      no spongiform change. Five aliquots of brain tissue from each of four brain
      regions were taken (cerebellum, medulla, frontal cerebral cortex and occipital
      cerebral cortex) from each of the 36 animals. One aliquot was frozen at -70
      degrees C, the others were subjected to one of four autolysis regimes at 3 or 7
      days at 25 degrees C or 37 degrees C. All samples were tested by Western
      immunoblotting for detection of PrP(Sc) using the Prionics - Check test (Prionics
      AG, Zurich, Switzerland). Further samples of medulla from 15 suspect scrapie
      cases, 10 healthy sheep, 13 suspect BSE cows and 5 healthy cows, were taken
      adjacent to the obex, and subjected to autolysis at 37 degrees C for 6, 12, 24
      and 48 hours before being fixed in 10 per cent formal saline and subsequently
      examined by a routine immunohistochemical technique for detection of PrP(Sc)
      protein. The abnormal protein could not be detected in any of the control animals
      by either technique. PrP(Sc) could be detected by Western immunoblotting in at
      least one brain area from all the positive animals after autolysis for 7 days at
      37 degrees C. The protein could be detected by immunohistochemistry in all cases
      which were positive by histopathological examination using all autolysis
      conditions. From the results of this study it is concluded that autolysis does
      not significantly compromise the diagnosis of scrapie or BSE by either of these
      diagnostic methods.

PMID- 12002637
TI  - Expression of tumour necrosis factor-alpha is associated with apoptosis in lungs
      of pigs experimentally infected with porcine reproductive and respiratory
      syndrome virus.
AB  - Expression of tumour necrosis factor (TNF)-alpha and its association with
      apoptosis was examined in lungs from pig experimentally inoculated with porcine
      reproductive and respiratory syndrome virus (PRRSV). The TNF-alpha nucleic acid
      was detected in PRRSV-infected alveolar macrophages by reverse transcription
      polymerase chain reaction (RT-PCR). The TNF-alpha antigen was detected in
      alveolar macrophages by immunohistochemisty. DNA fragmentation in apoptotic cells
      was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labelling (TUNEL). A double-labelling procedure using
      immunohistochemisty for the detection of PRRSV and the in situ TUNEL assay for
      the detection of apoptosis demonstrated that a majority of labelled cells were
      infected with PRRSV or apoptotic, but not both. Apoptotic cells were more
      abundant than PRRSV-infected cells in all lungs examined. A double-labelling
      procedure using immunohistochemisty for the detection of TNF-alpha and the in
      situ TUNEL assay for the detection of apoptosis demonstrated that a majority of
      labelled cells were apoptotic or for TNF-alpha, but not both. These data
      suggested that TNF-alpha released from macrophages after infection by PRRSV may
      induce apoptosis in uninfected bystander cells.

PMID- 12002638
TI  - A field study on the effect of in-feed inclusion of a natural zeolite
      (clinoptilolite) on health status and performance of sows/gilts and their
      litters.
AB  - The study was conducted to evaluate the effect of the long-term dietary use of a
      natural zeolite (clinoptilolite, NZ) on health status and reproductive
      performance of sows/gilts and performance of their litters, along with its
      compatibility with antibacterials (chlortetracycline, CTC) periodically used in
      medication programmes. Two hundred and forty sows/gilts and their litters were
      assigned to two main experimental groups and four subgroups, depending on the
      inclusion of NZ and CTC in their feed. During the trial, frequent sampling of
      pregnancy feed for mycotoxicological analysis revealed a high contamination level
      with zearalenone. No adverse or side effects attributed to NZ were noticed.
      Furthermore, the combined use of NZ and CTC revealed no clinically apparent
      interactive effect on the availability of the latter. Reproductive performance
      was significantly improved by the dietary inclusion of both NZ and CTC. The
      results also suggested that the beneficial effect of NZ could be additionally
      considered as an indicator of the amelioration of zearalenone exposure
      consequences.

PMID- 12002639
TI  - Effect of in-feed inclusion of a natural zeolite (clinoptilolite) on certain
      vitamin, macro and trace element concentrations in the blood, liver and kidney
      tissues of sows.
AB  - The study was conducted to evaluate, under field conditions, the effect of the
      long-term dietary use of a natural zeolite (clinoptilolite, CLI) and
      antibacterials (chlortetracycline, CTC) on the concentrations of certain vitamins
      (vitamin A and vitamin E) and minerals (K, Na, P, Ca, Mg, Cu and Zn) in blood and
      body tissues of the sow. Twenty-four sows were assigned to two main experimental
      groups and four subgroups, depending on the presence or absence of CLI and CTC in
      their feed, respectively. CLI was provided to the sows from weaning, during the
      service, gestation and lactation periods and up to the date of the next service,
      while CTC was administered for a 2-week period post-service, as well as for a 2
      week period following the allocation of the sows in the farrowing house, around 5
      days prior to the expected parturition. Blood samples were collected on the
      starting day of the trial, on the 30th and the 90th day of each pregnancy, on the
      day of each parturition and on the day of each weaning. Furthermore, 20 sows were
      similarly distributed in the same experimental groups and subgroups and at the
      end of the trial they were slaughtered and liver and kidney samples were
      collected for biochemical analysis. Neither CLI nor CTC supplementation of the
      diets had any significant effect on vitamins' and minerals' uptake and their
      distribution in the body, since there was no alteration in their blood serum and
      liver/kidney concentrations. Furthermore, no CLI x CTC interaction was noticed.

PMID- 12002640
TI  - Genetic characterisation of the Uruguayan Creole horse and analysis of
      relationships among horse breeds.
AB  - The genetic variability within the Uruguayan Creole horse and its relationship to
      a group of geographically or historically related breeds (Spanish Pure-bred,
      Barb, Quarter horse, Paso Fino, Peruvian Paso, Arabian and Thoroughbred horse),
      was evaluated using 25 loci (seven of blood groups, nine of protein polymorphisms
      and nine microsatellites) analyzed on a total of 145 Uruguayan Creole horses. In
      this study, blood group and protein polymorphism variants that are considered to
      be breed markers of Spanish Pure-bred and Barb horses were detected in the Creole
      breed. Conversely, some microsatellites and protein polymorphisms alleles were
      found uniquely in the Creole horse. American horse breeds together with Barb and
      Arabian horses clearly formed a separate cluster from the Spanish pure-bred and
      Thoroughbred breeds, as shown by an UPGMA dendrogram based on Nei's standard
      genetic distance. Data in this study provided evidence for considerable genetic
      variation within Uruguayan Creole horses and of a distinctive breed profile. Both
      traits were most likely inherited from the XVIth century Spanish horses, more
      closely related to Barb than to Spanish Pure-bred.

PMID- 12002641
TI  - Investigation of selenium content of eggs sampled from three major commercial
      cities along the lower reaches of the Changjiang River.
AB  - Eggs were collected from several supermarkets in Nanjing, Shanghai and Wuxi.
      Fluorospectrophotometry was used to determine the selenium (Se) content in egg
      white and yolk, and total Se was calculated. Results show that the range of total
      Se of eggs in the three regions was about 8-16 microg per egg, with Se mainly
      deposited in the yolk.

PMID- 12002642
TI  - Predictive values of serum and bulk milk sampling for the presence of
      persistently infected BVDV carriers in dairy herds.
AB  - The aim of this study was to examine whether it is possible to predict the
      presence of persistently infected (PI) animals with bovine viral diarrhoea virus
      on dairy farms in The Netherlands, based on a few blood samples of the herd,
      possibly in combination with a bulk milk test for antibodies. In 25 herds with,
      and 24 herds without, PI animal(s) the probabilities of obtaining at least x
      antibody positive animals out of a sample of n animals were calculated, with n
      varying from 3 to 7 and values for x that were considered were n, n - 1 to n - x.
      This probability, among animals 9-24 months old, ranged from 0.70 to 0.96 for
      herds with PI animals and from 0.13 to 0.37 for herds without. Using the result
      of bulk milk testing in addition did not add to the prediction. It was concluded
      that, due to the high percentage and large variation of antibody positive animals
      in herds without PI animals, it is not possible to predict the presence of PI
      animal(s) in dairy herds in The Netherlands using these methods.

PMID- 12002643
TI  - Canine visceral leishmaniasis: dog infectivity to sand flies from non-endemic
      areas.
AB  - Canine visceral leishmaniasis (VL), caused by Leishmania infantum (Leishmania
      chagasi in the New World), is a zoonotic, endemic disease in Western Europe and
      Latin America. The potential spreading to new regions was suggested by the
      appearance of canine VL among foxhounds in the US. Although the sand fly vectors
      in the major foci of transmission have been described, no information exists on
      other sand flies that could propagate the infection outside endemic areas. We
      evaluated the capacity of Lutzomyia shannoni (Dyar) and Lutomyia youngi
      (Feliciangeli & Murillo), which are widely distributed in the New World, to
      acquire L chagasi (Cunha and Chagas) infections. A high proportion of L youngi
      were infected after feeding on an oligosymptomatic dog (51 per cent) or a
      polysymptomatic individual (95 per cent), but the intensity of infection was low
      (< 200 promastigotes/fly). L shannoni became infected only by feeding on the
      polysymptomatic dog, and the infection rate was lower (9 per cent) than in
      Lutzomyia longipalpis (36 per cent), and Lutzomyia evansi (Nunez-Tovar) (Lutz and
      Neiva) (38 per cent), but the intensity of infection (200 to > 500
      promastigotes/fly) was comparable (L longipalpis) or higher (L evansi) than in
      the New World vectors. It is hypothesised that the presence of infected dogs in
      areas where L shannoni or L youngi occur could initiate new endemic cycles of VL
      in both South and North America.

PMID- 12002644
TI  - Composite integron array generated by insertion of an ORF341-type integron within
      a Tn21-like element.
AB  - Two class 1 integrons, In-t1 and In-t2, were previously identified in IncFI
      plasmids of Salmonella enterica serotype Typhimurium. Molecular analysis revealed
      a close physical link between the two integrons. In-t1 is preceded by the
      transposase genes of Tn21, whereas In-t2 is located downstream the 3'-conserved
      segment (3'-CS) of In-t1, in a head-to-tail configuration. In-t1 shows a peculiar
      sequence downstream the 3'-CS, containing an extended version of the open reading
      frame known as ORF341 (referred to as ORF341E) and a novel trimethoprim
      resistance gene, designated dfrA18. Retrospective analysis provided evidence for
      In-t1 insertion within Tn1935, a Tn21-related transposon identified in IncFI
      plasmids circulating among epidemic clones of multidrug-resistant S. enterica
      during the 1970s. Structural comparison between Tn21 derivatives from recent and
      ancestor IncFI plasmids showed that In-t2 has been conserved by these replicons.
      In-t1 belongs to a novel family of class 1 integrons containing the ORF341E
      sequence, and appears to have been acquired by IncFI plasmids after the assembly
      of Tn1935. In-t1 insertion occurred within the 5'-conserved segment (5'-CS)
      proximal region of the resident In-t2.

PMID- 12002645
TI  - The Entamoeba histolytica EhPgp5 (MDR-like) protein induces swelling of the
      trophozoites and alters chloride-dependent currents in Xenopus laevis oocytes.
AB  - Entamoeba histolytica, the protozoan responsible for human amoebiasis, presents
      the multidrug resistant phenotype due to the expression of the E. histolytica P
      glycoproteins EhPgpl and EhPgp5. Here, we studied the protein EhPgp5 encoded by
      the EhPgp5 gene in emetine-sensitive trophozoites transfected with the pEhNEOPgp5
      plasmid carrying the EhPgp5 gene. The transfected trophozoites increased their
      drug resistance slightly, but became bigger and globular. To investigate other
      EhPgp5 functions further, we microinjected the EhPgp5 mRNA in Xenopus laevis
      oocytes. Microinjected oocytes expressed EhPgp5 protein in their membranes and
      exhibited an ion current not present in the control oocytes. The antisense
      EhPgp5AS transcript, co-injected with the EhPgp5 mRNA, abolished the exogenous
      current, showing its specificity. Exogenous current was outward during
      depolarizing pulses. Reduction of the extracellular Cl- concentration displayed a
      reversible decrease of the current amplitude. Niflumic acid, 4,4
      diisothiocyanatostilbene-2, 2'-disulfonic acid, and other Cl- channel blockers
      abolished the exogenous current, which was poorly modified by verapamil and
      changes in osmolarity of the medium. Our results suggest that the EhPgp5 protein
      could function as a Cl- current inductor and as a coadjuvant factor to avoid drug
      accumulation in the cell.

PMID- 12002646
TI  - Increased prevalence of erythromycin resistance in streptococci: substantial
      upsurge in erythromycin-resistant M phenotype in Streptococcus pyogenes (1979
      1998) but not in Streptococcus pneumoniae (1985-1999) in Taiwan.
AB  - A total of 394 nonduplicate isolates of Streptococcus pyogenes collected from
      1979 to 1998 and 267 nonduplicate isolates of Streptococcus pneumoniae collected
      from October, 1998, to May, 1999, in Taiwan were evaluated. Among the 220
      erythromycin-resistant (MIC, > or =1 microg/ml) S. pyogenes isolates, 35% had an
      M phenotype and 65% had an ML phenotype (inducible resistance [iML], 0.5%, and
      constitutive resistance [cML], 64.5%). Among the 243 erythromycin-resistant S.
      pneumoniae isolates, the majority (65.4%) had an ML phenotype (iML, 0.4%, and
      cML, 65%) and 34.6% had an M phenotype. A substantial upsurge in the incidence of
      M-phenotype erythromycin-resistant isolates was found with time for S. pyogenes
      (0% in 1979-1984 and 100% in 1997-1998), and an increasing incidence of M
      phenotype among erythromycin-resistant S. pneumoniae was also noted (<20% before
      1994 and 45.4% in 1999). All S. pyogenes and all but four S. pneumoniae isolates
      exhibiting a cML or iML phenotype had harbored the ermAM gene. The presence of
      the mefA gene was demonstrated in all isolates of S. pyogenes and the mefE gene
      in all but four S. pneumoniae isolates exhibiting the M phenotype. Due to the
      increasing susceptibility of S. pyogenes and S. pneumoniae isolates to
      clindamycin, susceptibility tests of these two organisms to macrolides and
      clindamycin should be performed simultaneously in the clinical microbiology
      laboratory, particularly in areas with high rates of macrolide resistance.

PMID- 12002647
TI  - CTX-m-3 beta-lactamase-producing Escherichia coli from Greece.
AB  - An Escherichia coli clinical strain resistant to all beta-lactams except
      carbapenems was isolated in a Greek hospital. Analysis of beta-lactamase content
      by isoelectric focusing, PCR assays specific for various bla genes, and DNA
      sequencing showed that the strain produced TEM-1, a Citrobacter freundii AmpC
      related cephalosporinase, and CTX-M-3. The blaCTX.M-3 gene was carried by a 120
      kb plasmid that was readily transferable to a susceptible E. coli host.

PMID- 12002648
TI  - Erythromycin resistance in italian isolates of Streptococcus pyogenes and
      correlations with pulsed-field gel electrophoresis analysis.
AB  - Erythromycin resistance among Streptococcus pyogenes strains has been reported in
      Italy at high rates during the last few years. A total of 152 erythromycin
      resistant isolates of this species from southern Italian regions were
      characterized for the macrolide-resistance phenotype and screened by PCR for the
      corresponding genetic determinant. A close correlation was found between these
      phenotypic/genotypic data concerning macrolide resistance and results of Sma I
      macrorestriction fragment patterns (PFGE) analysis. In fact, the vast majority of
      the isolates assigned to individual PFGE classes mostly belonged to a single
      phenotype of macrolide resistance. All untypeable isolates belonged to the M
      phenotype. Twenty-two distinct PFGE types were recognized, of which 11 were
      recorded in only one isolate (one-strain type); about 50% of typeable isolates
      fell into five type clusters and 70% in seven. The increased erythromycin
      resistance among Italian isolates of S. pyogenes does not appear to be due to the
      spread of a single clone, but results indicate that the majority of group A
      streptococci examined are probably spread from a limited number of clones.

PMID- 12002649
TI  - Analysis of macrolide-lincosamide-streptogramin B (MLS(B)) resistance determinant
      in strains of Clostridium difficile.
AB  - The macrolide-lincosamide-streptogramin B (MLSB) resistance determinants have
      been detected among Clostridia in both C. perfringens and C. difficile strains.
      Previous studies have shown that MLSB-resistant C. difficile strains can be
      differentiated by specific hybridizing bands using an erm(B) probe. A recent
      study has demonstrated that C. difficile 630, a strain highly resistant to
      clindamycin and erythromycin (MIC > or = 256 ml/L), showing a hybridizing band at
      9.7 kb, contains two copies of an erm(B) gene. It was also hypothesized that C.
      difficile 630 erm(B) determinant has arisen from a progenitor, represented by the
      C. perfringens CP592 determinant, which contains only one copy of an erm(B) gene
      that differs from C. difficile 630 erm(B) for seven nucleotide substitutions. To
      investigate the possibility that C. difficile strains with hybridizing fragments
      of different molecular size have an erm(B) determinant not identical to the one
      described in C. difficile 630, we performed a genetic analysis on the erm(B)
      determinant in 18 C. difficile strains, isolated from different sources. The
      results showed a heterogeneity in erm(B) determinant: C. difficile strains with
      hybridizing bands at 7.3 or 3.7 kb contained only one erm(B) copy, whereas
      strains with a band at 9.7 kb had two copies. The majority of the toxigenic
      strains examined was characterized by only one erm(B) copy with a sequence
      identical to the one found in C. difficile 630 and a lower resistance level for
      erythromycin (MICs ranging from 16 to 24 ml/L). Differently, some strains had an
      erm(B) gene identical to the one found in C. perfringens CP592. PCR ribotyping
      and clustering analysis indicate that the examined resistant strains, except one,
      belong to the same genetic lineage. These results seem to support the hypothesis
      of the evolution of the C. difficile 630 erm(B) determinant. The functional
      significance of one or two copies of erm(B) gene in C. difficile strains should
      be further investigated.

PMID- 12002650
TI  - Validation of rapid screening tests for the identification of methicillin
      resistance in staphylococci.
AB  - The Velogene Rapid MRSA Identification Assay (Alexon-Trend Inc., Ramsey, MN), a
      commercially available 90-min genotypic test using a chimeric probe for the
      cycling-mediated recognition of the mecA gene in staphylococci, was compared with
      the MRSA-Screen latex agglutination test, a 15-min phenotypic test (Denka Seiken
      Co., Tokyo, Japan) for the identification of the mecA gene product PBP 2a. The
      results of both techniques were compared with mecA gene PCR. A total of 210 stock
      culture strains were tested, consisting of 108 methicillin-susceptible
      Staphylococcus aureus (MSSA) strains and 92 methicillin-resistant S. aureus
      (MRSA) strains. The performance of the assays was good, displaying sensitivities
      and specificities for Velogene and MRSA Screen of 96.7% and 100% and 96.7% and
      100%, respectively. Both Velogene and MRSA Screen could not correctly identify
      three of the MRSA strains each. Repeat testing with a larger inoculum or exposure
      of the three distinct strains to methicillin, respectively, resolved these
      problems. All MSSA strains as well as the other genera were correctly addressed
      by both techniques. The 10 methicillin-resistant Staphylococcus epidermidis
      strains were detected by both techniques. Both the Velogene and the MRSA Screen
      assays accurately identified mecA-positive staphylococcal strains and can be
      successfully used for routine application in clinical microbiology laboratories.

PMID- 12002651
TI  - Validation of diffusion methods for macrolide susceptibility testing of
      Helicobacter pylori.
AB  - Helicobacter pylori resistance to macrolides is increasing, and the need for
      susceptibility testing has become crucial. The only standardized method is agar
      dilution, which is not adapted to clinical practice. The present work aimed: (1)
      to optimize the technical conditions and to assess the reproducibility of the E
      test and disk diffusion method for macrolides susceptibility testing of H.
      pylori, and (2) to assess the performances of these two phenotypic methods in
      detecting strains harboring a resistance mechanism to macrolides. We used 191
      isolates collected in nine centers of France and Belgium. Phenotypic tests were
      performed on Mueller-Hinton agar supplemented with 10% horse blood, inoculated
      with a 2-day-old H. pylori suspension (10(8) CFU/ml), and incubated for 72 hr at
      37 degrees C under microaerophilic conditions. The reproducibility studied on two
      randomly selected strains was better for disk diffusion than for the E-test for
      both clarithromycin and erythromycin. For a subset of 10 strains, the MICs of
      erythromycin and clarithromycin did not differ from more than one two-fold
      dilution when determined by E-test or agar dilution method. The breakpoints were
      for MICs: 1 mg/L for both clarithromycin and erythromycin and for inhibition
      diameters, 22 mm for clarithromycin and 17 mm for erythromycin. There was a 100%
      concordance between susceptibility to erythromycin and clarithromycin. However,
      the susceptible and resistant populations were better separated by testing
      erythromycin. Of 34 resistant strains, two lacked the A2142G and A2143G point
      mutations in 23S rRNA by PCR-RFLP. None of 15 tested sensitive strains were
      positive for one of these two point mutations. For clinical practice, we
      recommend to assess macrolide susceptibility of H. pylori by using one of these
      two phenotypic methods under the described technical conditions.

PMID- 12002652
TI  - Characterization of haemophilus influenzae isolated from invasive disease in
      Brazil from 1990 to 1999.
AB  - The Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in
      the National Immunization Program in Brazil in the second half of 1999. A
      retrospective analysis on serotypes, biotypes, and antimicrobial resistance of Hi
      invasive strains obtained through Hi survey was conducted to document the
      characteristics of this pathogenic agent during a decade prior the use of Hib
      vaccine. A total 3,204 strains from 1990 to 1999 were studied, being 88.2%
      isolated from cerebrospinal fluid, 10.7% from blood, and 1.1% from pleural fluid.
      The rate of 90.9% of strains was obtained from children up to 4 years old, and
      the age group >6 months old to 1 year was the higher risk to Hi infection. Type b
      was, by far, the most common type (97.8%), followed in frequency by type a
      (0.5%); only 1.5% was a nontypable strain. Biotypes I and II accounted for 97.8%
      of isolates. Resistance to ampicillin (AM) and chloramphenicol (CO) was detected
      at rates of 18.1% and 19.1%, respectively, whereas simultaneous resistance to AM
      and CO was identified in 13.9% of strains. Total concordance was found between AM
      resistance and beta-lactamase production. No strain showed resistance to
      ceftriaxone and rifampicin. In conclusion, the data generated through this
      laboratory-based surveillance should serve as a reference for assessing the
      impact of Hib vaccination and to detect changes on the pattern of Hi diseases in
      the country.

PMID- 12002653
TI  - Streptococcus pneumoniae as an etiologic agent in infectious complications of
      pancreatic disease.
AB  - Systematic culturing of perioperative intra-abdominal samples allowed us to
      recognize the presence of Streptococcus pneumoniae in infectious complications of
      chronic pancreatitis in 9 male patients. In 8 of 10 of the intra- or
      peripancreatic samples, S. pneumoniae was the single isolate identified. All but
      one of the S. pneumoniae isolates were sensitive to penicillin. The patients had
      predisposing underlying conditions such as alcoholism and diabetes mellitus. All
      patients were cured due to adequate surgery and antibiotic treatment. Analysis of
      the case histories suggests that S. pneumoniae may have been a relevant organism
      causing the infectious complications of pancreatitis in these patients.

PMID- 12002654
TI  - Biochemical characterization of a novel extended-spectrum beta-lactamase from
      Pseudomonas aeruginosa 802.
AB  - Pseudomonas aeruginosa 802 was isolated at Rabta hospital in Tunis and was
      resistant to extended-spectrum cephalosporins and aztreonam. It produced a pI 7.6
      extended-spectrum beta-lactamase (ESBL). The ESBL, named LBT 802, was purified to
      homogeneity by filtration on Sephadex G-75 followed by CM-Sepharose
      chromatography and high-performance liquid chromatography (HPLC) on a TSK-gel SP
      5PW column. The LBT 802 enzyme had a molecular mass of 30 kDa. It showed a broad
      substrate profile by hydrolyzing benzylpenicillin, ampicillin, cephalothin,
      cephaloridine, cefotaxime, ceftriaxone, and cefpirome but not ceftazidime,
      cefoxitin, imipenem, or aztreonam. The highest hydrolytic efficiency (Vmax/Km)
      was obtained for ampicillin, cephalothin, cephaloridine, and benzylpenicillin.
      Among extended-spectrum cephalosporins the best substrate was ceftriaxone
      followed by cefotaxime and cefpirome. LBT 802 activity was inhibited by
      clavulanic acid, sulbactam, imipenem, cefoxitin, and aztreonam. It showed its
      lowest Ki values for clavulanic acid, imipenem and sulbactam.

PMID- 12002655
TI  - Aluminum ions induce DNA synthesis but not cell proliferation in human
      fibroblasts in vitro.
AB  - The effect in vitro of aluminum (Al) ions on DNA synthesis and human dermal
      fibroblast proliferation using [Al] concentrations from 1.85 to 74 microM and
      incubation periods of 1, 2, 3, 4, and 5 d was assessed. The lowest concentration
      of Al that exerted a slight positive, although not significant, effect on DNA
      synthesis was 1.85 microM, after d 3 or 5 of incubation. The stimulating action
      of Al was more evident and statistically significant from concentrations of 3.7
      microM and 2 d exposure onward. This Al-induced effect on [3H] thymidine
      incorporation into DNA increased in a time-dependent manner as [Al] in the
      culture medium rose, provoking increments of up to 322% above the control at [Al]
      74 microM and 5 d incubation. In contrast, Al salts moderately increased
      fibroblast division in a continuous manner only from 7.4 to 74 microM after 3 d
      of incubation. Although significant overall, the minimal and inconstant mitogenic
      activity of Al differs greatly from and is not parallel to DNA synthesis, which
      is not clearly related to exposure times or Al concentrations. Abnormalities in
      Al-induced cellular metabolic processes described herein and their influence on
      the cell cycle may constitute a toxicity mechanism for human tissues, leading to
      disease development. Further studies are required to determine whether these
      findings can be extrapolated to in vivo situations.

PMID- 12002656
TI  - Comparison of the cytotoxicity, cellular uptake, and DNA-protein crosslinks
      induced by potassium chromate in lymphoblast cell lines derived from three
      different individuals.
AB  - We are trying to understand individual differences in susceptibility to chromate
      toxicity by comparing three different lymphoblastic cell lines derived from three
      different individuals. We have compared the uptake of CrO4(2-), the release of
      LDH from cells, the proliferation ability of the cells, and the DNA-protein
      crosslinks in these lymphoblastic cell lines exposed to chromate. We report here
      that one lymphoblastic cell line, GM0922B, appears to be considerably less
      sensitive than the other two cells lines to the cytotoxic effects of hexavalent
      chromium. The diminished sensitivity is almost twofold and can be accounted for
      by the decreased uptake of hexavalent chromium, which results in less lactate
      dehydrogenase release, and greater tolerance to chromate inhibition of cell
      proliferation and less DNA-protein crosslinking. This lower uptake of chromate
      combined with interindividual differences in extracellular Cr(VI) reducing
      capacity are probably the two most important determinants of genetic
      susceptibility to chromate toxicity.

PMID- 12002657
TI  - Elements of calcified sites in human thoracic aorta.
AB  - To elucidate the manner of element accumulation in the arteries with aging, the
      authors investigated the element contents in the calcified and surrounding sites
      of the thoracic aortas by inductively coupled plasma-atomic emission
      spectrometry. The subjects consisted of three men and five women, ranging in age
      from 45 to 99 yr. The calcified, calcification-surrounding, and control (which
      appeared normal) sites were removed from the thoracic aortas and the element
      contents were determined. It was found that the contents of calcium, phosphorus,
      magnesium, zinc, and aluminum were higher in the calcified site than in the
      control site, whereas the contents of sulfur, iron, and lead were lower in the
      calcified site than in the control site. The contents of the elements in the
      surrounding site were intermediate between those of the calcified and control
      sites, except for the magnesium and lead contents, which were the lowest. The
      mass ratios of magnesium to calcium and phosphorus were lower in the calcified
      site compared with the surrounding and control sites, and as calcium and
      phosphorus increased in the aorta, the mass ratios lowered gradually in the
      aorta.

PMID- 12002658
TI  - Influence of chelation and oxidation state on vanadium bioavailability, and their
      effects on tissue concentrations of zinc, copper, and iron.
AB  - Today, vanadium compounds are frequently included in nutritional supplements and
      are also being developed for therapeutic use in diabetes mellitus. Previously,
      tissue uptake of vanadium from bis(maltolato)oxovanadium(IV) (BMOV) was shown to
      be increased compared to its uptake from vanadyl sulfate (VS). Our primary
      objective was to test the hypothesis that complexation increases vanadium uptake
      and that this effect is independent of oxidation state. A secondary objective was
      to compare the effects of vanadium complexation and oxidation state on tissue
      iron, copper, and zinc. Wistar rats were fed either ammonium metavanadate (AMV),
      VS, or BMOV (1.2 mM each in the drinking water). Tissue uptake of V following 12
      wk of BMOV or AMV was higher than that from VS (p < 0.05). BMOV led to decreased
      tissue Zn and increased bone Fe content. The same three compounds were compared
      in a cellular model of absorption (Caco-2 cells). Vanadium uptake from VS was
      higher than that from BMOV or AMV at 10 min, but from BMOV (250 microM only, 60
      min), uptake was far greater than from AMV or VS. These results show that neither
      complexation nor oxidation state alone are adequate predictors of relative
      absorption, tissue accumulation, or trace element interactions.

PMID- 12002659
TI  - Log-normal distribution of the trace element data results from a mixture of
      stocahstic input and deterministic internal dynamics.
AB  - In previous article, we showed a log-normal distribution of boron and lithium in
      human urine. This type of distribution is common in both biological and
      nonbiological applications. It can be observed when the effects of many
      independent variables are combined, each of which having any underlying
      distribution. Although elemental excretion depends on many variables, the one
      compartment open model following a first-order process can be used to explain the
      elimination of elements. The rate of excretion is proportional to the amount
      present of any given element; that is, the same percentage of an existing element
      is eliminated per unit time, and the element concentration is represented by a
      deterministic negative power function of time in the elimination time-course.
      Sampling is of a stochastic nature, so the dataset of time variables in the
      elimination phase when the sample was obtained is expected to show Normal
      distribution. The time variable appears as an exponent of the power function, so
      a concentration histogram is that of an exponential transformation of Normally
      distributed time. This is the reason why the element concentration shows a log
      normal distribution. The distribution is determined not by the element
      concentration itself, but by the time variable that defines the pharmacokinetic
      equation.

PMID- 12002660
TI  - Vitamin E and selenium administration as a modulator of antioxidant defense
      system: biochemical assessment and modification.
AB  - Exposure of cells to ionizing radiation leads to the formation of reactive oxygen
      species (ROS) that are associated with radiation-induced cytotoxicity. Because of
      the serious damaging potential of ROS, cells depend on the elaboration of the
      antioxidant defense system (AODS), both enzymatic and nonenzymatic oxidant
      defense mechanisms. The deficiency in important components of the endogenous AODS
      leads to the accumulation of oxidative stress inducing oxidative damage. The
      antioxidant enzymes superoxide dismutase and glutathione peroxidase are key
      intracellular antioxidants in the metabolism of ROS. In the current study, we
      investigated the potential role of these antioxidant enzymes in radioresistance
      during the evaluation of the compensatory role of some exogenous micronutrients
      against oxidative stress Animals were categorized into eight groups, receiving
      vitamin E (alpha-tocopherol) and/or selenium (Se) with or without whole-body
      gamma-irradiation (6.5 Gy). The results indicate that antioxidant pretreatments
      before irradiation may have some beneficial effects against irradiation-induced
      injury. The results also indicate that selenium and vitamin E act alone and in an
      additive fashion as radioprotecting agents. The results further suggest that
      selenium confers protection in part by inducing or activating cellular free
      radical scavenging systems and by enhancing peroxide breakdown, whereas vitamin E
      appears to confer its protection by an alternate complementary mechanism.

PMID- 12002661
TI  - Investigation of the elemental distribution in iliac crests of female New Zealand
      rabbits using NAA.
AB  - This article deals with an osteoporosis model using New Zealand rabbits in order
      to study the function of inorganic elements for women patients with osteoporosis.
      Thirty cases of iliac crests were collected and determined using the neutron
      activation analysis technique. The results show that the fluorine concentrations
      in the experimental group are higher than those in the control group and that the
      magnesium concentrations are significantly lower (p < 0.001), but the
      concentrations of potassium, sodium, calcium, barium, manganese, and strontium
      show no significant differences. Combined with the serum biochemical markers of
      bone formation and resorption, the physiological functions of some metal elements
      in bone are also discussed.

PMID- 12002662
TI  - The lipophilic iron compound TMH-ferrocene [(3,5,5-trimethylhexanoyl)ferrocene]
      increases iron concentrations, neuronal L-ferritin, and heme oxygenase in brains
      of BALB/c mice.
AB  - Mismanagement of intracellular iron is a key pathological feature of many
      neurodegenerative diseases. Our long-term goal is to use animal models to
      investigate the mechanisms of iron neurotoxicity and its relationship to
      neurodegenerative pathologies. The immediate aim of this experiment was to
      determine regional distribution of iron and cellular distribution of iron storage
      proteins (L- and H-ferritin) and an oxidative stress marker (heme oxygenase-1) in
      brains of mice fed the lipophilic iron compound (3,5,5-trimethylhexanoyl) (TMH)
      ferrocene. We fed male and female weanling BALB/cj mice diets either deficient in
      iron (0 mg Fe/kg diet), adequate in iron (35 mg Fe/kg diet; control mice), or
      adequate in iron and supplemented with 0.1 or 1.0 g TMH-ferrocene/kg diet for 8
      wk. Iron concentrations in cerebrum were higher in mice fed 1.0 g TMH
      ferrocene/kg diet than in control mice (p < 0.05). Liver iron concentrations were
      eightfold higher in mice fed 1.0 g TMH-ferrocene/kg diet than in control mice (p
      < 0.0001). L-Ferritin and heme oxygenase-1 expression were elevated in striatum
      in mice fed 1.0 g TMH-ferrocene/kg diet. We conclude that administration of the
      lipophilic iron compound TMH-ferrocene leads to subtle perturbations of cellular
      iron within the brain, potentially representing a model of iron accumulation
      similar to that seen in various neuropathological conditions.

PMID- 12002663
TI  - Aluminum neurotoxicity is reduced by dantrolene and dimethyl sulfoxide in
      cultured rat hippocampal neurons.
AB  - Cell death was reduced in cultured rat hippocampal cells treated with aluminum
      chloride by dantrolene and dimethylsulfoxide, indicating aluminum toxicity may be
      mediated through release of calcium from intracellular stores and oxidative
      stress. Cell death was reduced to a lesser degree by cycloheximide and
      actinomycin D, indicating some evidence for apoptosis, however apoptosis did not
      appear to be a major cause of cell death from aluminum toxicity.

PMID- 12002664
TI  - A comparison of the efficacy and tolerability of 0.5% timolol maleate ophthalmic
      gel-forming solution QD and 0.5% levobunolol hydrochloride BID in patients with
      ocular hypertension or open-angle glaucoma.
AB  - The purpose of this study was to compare the ocular hypotensive efficacy and
      tolerability of 0.5% timolol maleate ophthalmic gel-forming solution (timolol
      gel) and 0.5% levobunolol hydrochloride (levobunolol). This was a randomized,
      double-masked, multi-center, active-controlled, 2-period, crossover study. After
      a 3-week, single-masked placebo run-in phase, patients with ocular hypertension
      or open-angle glaucoma and an intraocular pressure (IOP) > or = 22 mmHg were
      randomized to receive timolol gel QD or levobunolol BID for 6 weeks followed by a
      3-week, placebo washout period. Patients were then crossed over to the alternate
      treatment for 6 weeks. IOP and heart rate (HR) were measured at 3 and 6 weeks
      after the start of therapy with either timolol gel or levobunolol. Of 133
      patients randomized, 116 received both treatments. Timolol gel QD was comparable
      to levobunolol BID in reducing trough and peak IOP. At trough, HR was marginally
      increased with timolol gel and was decreased with levobunolol (p = < 0.001). At
      peak, HR was decreased with both treatments, but the decrease was significantly
      less with timolol gel than with levobunolol (p = 0.049). Significantly more
      patients experienced at least one adverse event (p = 0.024), adverse events
      related to special senses (p = 0.002), and burning and stinging (p < 0.001) with
      levobunolol compared to timolol gel. The study demonstrates that timolol gel QD
      has IOP-lowering effects comparable to those of levobunolol BID with fewer
      adverse experiences and less effect on HR.

PMID- 12002665
TI  - Effects of sympathetic nerve stimulation on long posterior ciliary artery blood
      flow in cats.
AB  - A new technique using ultrasonic flowmetry was developed in order to directly
      measure blood flow in the long posterior ciliary artery (LPCA) of anesthetized
      cats. Basal LPCA blood flow averaged about 0.6 ml/min and was stable over the
      experimental period. Electrical stimulation of the cervical preganglionic
      cervical sympathetic nerve produced frequency-dependent anterior segment ocular
      vasoconstrictor responses. Ipsilateral nictitating membrane contractions were
      simultaneously measured as a well-established index of neural sympathetic
      activation. LPCA frequency-response relationships were shifted to the right in
      comparison with those for the nictitating membrane. When elicited at two min
      intervals, submaximal evoked responses of both systems were stable for more than
      90 min. Ocular vasoconstrictor and nictitating membrane responses were blocked in
      a dose-dependent fashion by intravenous treatment with the non-selective a
      adrenoceptor antagonist, phentolamine (0.3-3.0 mg/kg), as well as with the
      selective alpha1-adrenoceptor antagonist, prazosin (3-30 microg/kg). In contrast,
      neither evoked response was further antagonized by subsequent administration of
      the alpha2-adrenoceptor antagonist, yohimbine (500 microg/kg). These results
      demonstrate the usefulness of ultrasonic flowmetry to study mechanisms
      controlling ocular anterior segment circulation and suggest that, as previously
      established for the nictitating membrane and anterior choroid, adrenergic
      neurogenic vasoconstriction in tissues perfused by the LPCA is mediated
      predominantly by alpha1-adrenoceptors.

PMID- 12002666
TI  - Bioavailability in the human eye of a fixed combination of latanoprost and
      timolol compared to monotherapy.
AB  - The ocular pharmacokinetics of a single topical administration of a fixed
      combination (FC) of latanoprost 0.005% and timolol 0.5% was compared to the
      monotherapies of latanoprost and timolol in cataract surgery patients. The
      absorption rate of latanoprost and timolol into the aqueous humor was similar
      after administration of the FC compared to the two drugs given separately. The
      aqueous humor concentration of the acid of latanoprost tended to be higher 1-4
      hours after administration of FC compared to latanoprost monotherapy. This
      resulted in an increased AUC. The Tmax and elimination half-life of both
      latanoprost and timolol were similar after administration of either FC or the two
      drugs given as monotherapy. Latanoprost did not have any influence on the ocular
      pharmacokinetics of timolol. The bioavailability of latanoprost and timolol into
      human aqueous humor, after FC, was at least as good as for the two drugs
      administered separately.

PMID- 12002667
TI  - Dose response of dexamethasone for the enhanced ocular hypotensive response to
      epinephrine in rabbits with prior dexamethasone treatment.
AB  - We have previously shown that administration of epinephrine to the rabbit eye
      with dexamethasone pretreatment resulted in a significant decrease in intraocular
      pressure (IOP), compared to the use of epinephrine alone. Furthermore, this
      decrease in IOP is dose-dependent on epinephrine with the largest response of
      decrease of IOP occurring at the lower doses of epinephrine. We now extend this
      study to determine whether the decrease in IOP is dose-dependent on
      dexamethasone. Rabbit eyes were pretreated with five applications of topical
      dexamethasone or saline, administered at fifteen-minute intervals. Eyes were then
      treated with 0.005% epinephrine (0.01% epinephrine bitartrate). IOP was monitored
      for the next four hours. Different groups of rabbits received varying
      concentrations of dexamethasone base, from 0.0004% to 0.07% (dexamethasone
      phosphate), and a dose response curve was obtained. When compared to eyes treated
      with epinephrine alone, eyes pretreated with dexamethasone showed a significantly
      greater decrease in pressure at free base dexamethasone concentrations of 0.07%,
      0.007% and 0.0007%, with the greatest difference at the 0.007% concentration
      (mean = 6.8 mm Hg). Similarly, the duration taken for the IOP to return to
      baseline levels was prolonged in the groups receiving dexamethasone pretreatment.
      The synergism between dexamethasone and epinephrine in lowering IOP may be a
      useful alternative in the treatment of ocular hypertension and glaucoma
      especially using a combination of a low dose of epinephrine with a low dose of
      dexamethasone.

PMID- 12002668
TI  - Pharmacological and molecular biological (RT-PCR) characterization of functional
      TP prostanoid receptors in immortalized human non-pigmented ciliary epithelial
      cells.
AB  - Immortalized human non-pigmented ciliary epithelial (NPE) cells (ODM-2) were
      shown to express the mRNA for the prostanoid TPalpha but not the TPbeta receptor
      using reverse transcription-polymerase chain reaction (RT-PCR). These TPalpha
      receptors were coupled to phospholipase C (PLC) and, thus, promoted
      phosphoinositide (PI) turnover. TP receptor agonists yielded the following
      potencies (EC50S) in the PI turnover assays: I-BOP = 8.2 +/- 1.1 nM; carbocyclic
      TA2 = 87.5 +/- 25.3 nM; U-44069 = 1.16 +/- 0.32 microM; U-46619 = 1.2 +/- 0.2
      microM (n = 4-17). Agonists selective for other prostanoid receptor subtypes
      (e.g., fluprostenol and sulprostone) were inactive. The agonist effects of U
      44619 and I-BOP were potently blocked, in an apparent non-competitive manner (ki
      = 53.9 +/- 12 nM; pA2s = 7.6-7.8; pKbs = 7.38), by the TP receptor-selective
      antagonist, SQ29,548, but were unaffected by other prostanoid receptor
      antagonists (e.g., AH6809, AL-8810). The PLC inhibitor (U73122) inhibited U-46619
      induced PI turnover (IC50 = 4.3 +/- 0.6 microM). The functional potencies of the
      compounds stimulating or inhibiting the TP receptor-mediated PI turnover in the
      NPE cells correlated well with the TP receptor binding affinities of these
      compounds at human platelet TP receptors (r = 0.98). These studies have shown the
      presence of the mRNA for and the expression of functional TPalpha receptors
      coupled to PLC in human NPE cells. The TPalpha receptors on NPE cells may be
      responsible for inhibiting aqueous humor production and may help explain the
      intraocular pressure-lowering effects of certain TP agonists.

PMID- 12002669
TI  - Comparison of an immortalized human corneal epithelial cell line and rabbit
      corneal epithelial cell culture in cytotoxicity testing.
AB  - The cytotoxicity of benzalkonium chloride (BAC) and disodium edetate (EDTA) was
      evaluated in vitro in rabbit corneal epithelial primary cells and in the
      immortalized human corneal epithelial cell line SV40. Cell injury was assessed by
      lactate dehydrogenase (LDH) leakage and by reduction of the tetrazolium salt WST
      1 to formazan by mitochondrial metabolic activity. Cell cultures were exposed to
      test compounds both in serum-free and in serum-containing medium. Although WST-1
      and LDH tests measured different physiological endpoints, they yielded comparable
      results. However, the LDH test seemed less reliable due to great variation. The
      use of serum was found to result in lower toxicity of the compounds in both
      tests. The rabbit primary cell culture and the human corneal cell line were quite
      similar in their responses to BAC and EDTA. The human cell line is a promising in
      vitro alternative in oculotoxicity testing.

PMID- 12002670
TI  - Ocular drug permeation following experimental excimer laser treatment on the
      isolated pig eye.
AB  - Excimer laser photorefractive keratectomy (PRK) is a well-established procedure
      which is frequently applied to correct myopia. Since structural alterations of
      the corneal epithelium occur after the treatment, a different drug permeation can
      be assumed. To investigate the effects of PRK on drug permeation, excimer laser
      ablations with varying depths were performed on isolated pig eyes. The permeation
      of lipophilic (diclofenac-sodium; D-Na) and hydrophilic (pilocarpine
      hydrochloride; P-HCl model drugs were studied in vitro. Under these experimental
      conditions, P-HCl demonstrated a significant (p < 0.05) enhancement of permeation
      in relation to the ablation depth. In contrast, corneal epithelial thickness
      scarcely influenced the permeation rate of D-Na. Not until removing the entire
      epithelium did a significantly increased permeability occur, when compared to
      untreated cornea. These results suggest that PRK may significantly reduce the
      corneal barrier function and alter pharmacokinetics of topical medication.

PMID- 12002671
TI  - 99mTc-diflunisal and the human iris: topical application reveals localization.
AB  - Following the instillation of a drug into the eye, drainage mechanisms will
      commence at once. In this report, an attempt was made to assess the dynamics of
      an instilled nonsteroidal anti-inflammatory drug (NSAID), diflunisal, labeled
      with 1 MBq 99mTc followed by twenty minutes of scintigraphy. The results obtained
      with this labeled drug were compared with instillation of the same volume and
      activity of 99mTcO4-. Although the pertechnetate anion is an excellent and
      innocuous indicator for detecting the external lacrimal drainage system of the
      eye, it cannot visualize the internal structures. A clear scintigraphic
      difference was noted between labeled diflunisal and the pertechnetate anion.
      Scintigraphic activity surrounding the pupil of the eye provides evidence of
      visualization of the iris/ciliary body. This seems reasonable as the
      cyclooxygenase enzyme is located in this structure, and NSAIDs exert their
      mechanism of action via this complex. With this technology, visualization of some
      internal structures of the eye may be facilitated.

PMID- 12002672
TI  - Pharmacokinetics and bioavailability of a Ginkgo biloba extract.
AB  - The aim of the present study was to assess the bioavailability of the main active
      ingredient in Ginkgo biloba extract, ginkgolid B. The study also focused on the
      pharmacokinetics of two different dosage regimens for orally administered Gingko
      biloba extract, 80 mg once daily and 40 mg twice daily for 7 days. Twelve healthy
      volunteers took part in the study. They were randomly assigned to one of the two
      treatment groups: 40 mg twice daily or 80 mg once daily, with an interval of 21
      days between cycles. Statistical analysis was used to assess the main
      pharmacokinetic parameters. The results show that a dosage of 40 mg twice daily
      (every 12 hrs) is accompanied by a significantly longer half-life (t1/2) and mean
      residence time (MRT) than a single 80 mg dose, even though the latter causes a
      higher concentration peak (Cmax). The maximum concentration time (Tmax) is 2.3
      hrs after administration in both treatments.

PMID- 12002673
TI  - The efficacy of brimonidine in preventing intraocular pressure elevation in the
      provocative test for primary angle-closure glaucoma.
AB  - The purpose of this study was to evaluate the efficacy of 0.2% brimonidine
      tartrate in preventing intraocular pressure (IOP) elevation in the dark-prone
      provocative test for primary angle-closure glaucoma (PACG). Twenty-two eyes from
      22 patients with angle-closure glaucoma were enrolled in this study. Each of the
      selected eyes had previously tested positive in a recent dark-prone test. One
      drop of 0.2% brimonidine tartrate was then instilled in each eye 2 hours prior to
      a second dark-prone test. An IOP elevation of greater than 8 mmHg was regarded as
      a positive result. The IOP elevation in the first dark-prone test was 11.91 +/-
      5.17 (range: 5.7 - 27.3) mmHg, while the IOP only increased 5.70 - 2.96 (range:
      2.9 - 12.2) mmHg in the second dark-prone test that was pre-treated with 0.2%
      brimonidine tartrate (p < 0.001). A significant difference was also noted in the
      pre-test IOP (15.59 +/- 3.86 mmHg vs. 13.33 +/- 3.65 mmHg, p = 0.008) as well as
      in the post-test IOP (27.62 +/- 7.27 mmHg vs. 19.03 +/- 3.50 mmHg, p < 0.001) in
      the two sequential dark-prone tests. All but three of the initially positive dark
      prone tests (86.46%) converted to negative tests after pre-treatment with
      brimonidine. There was a significant effect of 0.2% brimonidine tartrate in the
      prevention of IOP elevation in PACG patients previously found to test positive in
      the dark-prone provocative test.

PMID- 12002674
TI  - DNA vaccine against Friend erythroleukaemia virus.
AB  - Plasmids carrying DNA copies of the gag and env genes of FV, which causes
      erythroleukaemia in susceptible mouse strains, were prepared. Expression of the
      cloned genes was confirmed by indirect immunofluorescence in cells transfected in
      vitro. Immunization experiments were performed in DBA/2 mice. Animals were
      injected with three doses of plasmid either intramuscularly (100 microg DNA per
      dose) or intradermally (1 microg DNA per dose); in the latter case, a gene gun
      was used. The FV type A or P was used as a challenge. The immunization with gag-
      and env-derived vaccines resulted in protective immunity in a high proportion of
      mice.

PMID- 12002675
TI  - Antiapoptotic cytokine IL-3 + SCF + FLT3L influence on proliferation of gamma
      irradiated AC133+/CD34+ progenitor cells.
AB  - Recovery from radiation-induced bone marrow aplasia depends on appropriate
      cytokine support. The aim of our work was to find a cytokine combination allowing
      in vitro gamma-irradiated (2.5 Gy) CD34+/AC133+ haematopoietic stem cells to
      evade radiation-induced apoptosis and to enhance damage reparation, which should
      enable proliferation and ex vivo expansion of cells. Cells were isolated using
      separation in a Cobe separator followed by immunomagnetic selection by antibody
      against the AC133 antigen. Thus isolated cells were 80% AC133+/CD34+ and 10% of
      them expressed the CD33+ antigen. Ten thousand of AC133+ cells formed 1146 CFU-GM
      and 304 BFU-E. We proved a high expansion efficiency of cytokine combination SCF
      + IL-3 + FLT3L in comparison with the combination SCF + IL-3 + IL-11 in both, non
      irradiated cells and cells irradiated with a dose of 2.5 Gy. The D0 value for
      AC133+ cells was determined by the clonogeneity test. The D0 value for CFU-GM was
      estimated to be 1.08 Gy and for BFU-E 0.95 Gy. The results of DNA analysis showed
      that the majority of isolated AC133+ cells were in G0/G1 phase of the cell cycle.
      We proved that the dose of 2.5 Gy induced massive apoptosis (80%) of these cells
      without progression through the cell cycle, which indicates interphase cell
      death. Under the influence of cytokine combination (SCF + IL-3 + FLT3L), the
      surviving 20% of cells entered the cell cycle and, similarly to non-irradiated
      control cells, on 7th day 35% of cells were in S phase.

PMID- 12002676
TI  - Apoptosis induction in lymphoma cells: thiol deprivation versus thiol excess.
AB  - We studied the effects of thiol availability on apoptosis induction in B-cell
      lymphoma 38C13, T-cell lymphoma EL4, and also other cells. Compounds with a free
      SH group are required for survival and growth of 38C13 cells but not of EL4
      cells. Thiol deprivation (2-mercaptoethanol concentrations about 0.3 microM and
      lower) induced apoptosis in 38C13 cells. On the other hand, thiol excess (2
      mercaptoethanol concentrations higher than 300 microM) induced apoptosis in 38C13
      cells and EL4 cells as well as in other cells (e.g. Raji, HeLa). L-cystine and
      non-thiol antioxidant ascorbic acid were unable to support survival of 38C13
      cells. Ascorbic acid induced cell death at concentrations higher than 600 microM.
      Thiol cross-linking compound diamide (100 microM and higher) abrogated the
      survival-supporting effect of 2-mercaptoethanol (50 microM). Apoptosis induction
      by thiol deprivation and by thiol excess was not directly related to a specific
      significant change in the p53 level or p53 activation. Apoptosis induction by
      thiol excess was associated with a certain decrease in the Bcl-2 level while the
      Bax level did not change. We conclude that both thiol deprivation and thiol
      excess can induce apoptosis in lymphoma cells. Apoptosis induction by thiol
      deprivation is specifically related to the presence of a free SH group. However,
      apoptosis induction by thiol excess does not seem to be specifically related to
      the presence of a free SH group. It probably results from the excess of a
      reductant. Apoptotic control protein p53 does not seem to play a significant role
      in apoptosis induction either by thiol deprivation or by thiol excess.

PMID- 12002677
TI  - An ATP-dependent step is required for the translocation of microinjected
      precursor mRNA into nuclear speckles.
AB  - Nuclear speckles (speckles) represent a distinct nuclear compartment within the
      interchromatin space and are enriched in splicing factors. In a previous study
      (Melcak et al., 2001), it has been shown that the pre-spliceosomal assembly on
      microinjected splicing-competent precursor mRNA takes place in the speckles, and
      it has been suggested that the targeting of RNA into speckes consists of two
      interdependent steps, namely the diffusion process, followed by the energy
      dependent translocation of RNA into the speckles. In the present study, we
      confirm the existence of these two steps and show that this latter translocation
      is ATP dependent.

PMID- 12002678
TI  - Expression of protein tyrosine kinase pp60v-src variants in Dictyostelium
      discoideum.
AB  - We achieved production of v-Src of the low-oncogenic PRC and its variant proviral
      structure H19 in Dictyostelium discoideum, an emerging host system suitable for
      synthesis of heterologous proteins. To accomplish their expression, the first six
      codons of the N-terminus of v-src had to be changed according to the D.
      discoideum codon preference. Alternatively, N-terminal fusions of 6xHis-tag or
      GFP were sufficient to overcome the incompatibility in codon usage. D. discoideum
      expressed v-Src kinases of the expected molecular weight were recognized by Src
      specific antibodies; GFP-PRC was distributed uniformly in the cytosol. In
      contrast to other lower eukaryotes, where the accumulation of v-Src leads to
      growth inhibition, D. discoideum cells silenced the kinase activity of PRC
      derived v-Src and showed no developmental or growth defects.

PMID- 12002679
TI  - Monoclonal antibody KN-01 against the heavy chain of kinesin.

PMID- 12002680
TI  - Influence of dietary fat on beta-carotene absorption and bioconversion into
      vitamin A.
AB  - Dietary fat facilitates the utilization of carotenoids and, based on serum beta
      carotene or retinol responses following ingestion of meals containing carotene
      and fat sources, it has been reported that the amount of fat required in a meal
      may be minimal (approximately 3-5 g). However, the dietary fat requirement for
      optimal carotene utilization in humans cannot be fully ascertained without longer
      term dose-response studies that measure the changes in vitamin A body stores in
      response to varying levels of dietary fat. In humans, vitamin A body stores can
      be determined by use of stable isotope-dilution methods. Animal studies have
      shown that although the level of dietary fat has no effect on serum vitamin A
      concentrations of animals fed beta-carotene, higher liver vitamin A
      concentrations were found in those that ingested higher fat levels. Other factors
      that might influence the relationship of fat intake and beta-carotene utilization
      include the type of fat ingested, physicochemical properties of the carotenoid
      source, amount of carotene ingested, whether fat and beta-carotene sources are
      provided in the same meal, the presence of helminthic infections, age, and
      vitamin A status.

PMID- 12002681
TI  - Nutritional rickets: an old disease returns.
AB  - Nutritional rickets, an ancient disease that was thought to have been cured in
      the early part of the 20th century, has made an unexpected comeback in recent
      years throughout the world. Although the frequency of its occurrence is poorly
      documented, increasing case reports of rickets are apparently related to low
      dietary intake of vitamin D and calcium and decreased sunshine exposure. Greater
      awareness of this problem is needed, as are further data regarding vitamin D
      status and incidence of rickets among infants and toddlers. Routine provision of
      supplemental vitamin D to all breastfed infants remains controversial, but may
      become more widely recommended.

PMID- 12002682
TI  - Mortality in patients with celiac disease.
AB  - Celiac disease is an autoimmune disorder triggered by ingestion of gluten
      containing foods. Epidemiologic studies dating from the 1950s established its
      association with gastrointestinal malignancies, particularly small bowel
      lymphoma. Corrao et al. recently demonstrated that patients with celiac disease
      are at increased risk of mortality. Further, this risk is directly related to
      compliance with a gluten-free diet. Continued research is needed regarding the
      development of malignant complications related to celiac disease.

PMID- 12002683
TI  - Can vitamin D supplementation in infancy prevent type 1 diabetes?
AB  - Several recent European studies suggested that supplementing infants with vitamin
      D during their first year might prevent type 1 diabetes. A dose of 50 microg/day
      was associated with decreased diabetes risk in Finland, but the effectiveness of
      lower doses was not examined. The recommended dietary intake of vitamin D for
      U.S. infants is 5 microg/day and the tolerable upper level is 25 microg/day.
      There is no evidence that intakes between 5 and 25 microg/day would reduce
      diabetes incidence, but it would seem prudent to ensure that infants reach at
      least the lower end of this range.

PMID- 12002684
TI  - Cellular transporters for zinc.
AB  - Nutritionally essential metals such as zinc are moved into and out of cells by a
      series of transport proteins or transporters. Their tri-fold purpose is to
      procure zinc from the environment, to protect cells against zinc toxicity, and
      maintain ample supplies of zinc for metabolic purposes. Two families of zinc
      transporters are known: the ZIP family that imports zinc and the ZnT family that
      functions in releasing zinc or sequestering zinc internally.

PMID- 12002685
TI  - Cheese consumption and the development and progression of dental caries.
AB  - Whereas research into the causes of dental decay has focused on the harmful
      relationship between dental plaque bacteria and foods, studies into the
      protective effects of foods have been infrequent and limited in number. Recent
      investigations showed that milk and cheese could reduce the effects of metabolic
      acids, and could help restore the enamel that is lost during eating. Postulated
      mechanisms involve buffering, salivary stimulation, reduction of bacterial
      adhesion, reduction of enamel demineralization, and/or promotion of
      remineralization by casein and ionizable Ca and P. Given this information,
      consumers may be motivated to use milk and cheese to reduce, or reverse the
      cariogenic effects of many other foods.

PMID- 12002686
TI  - Effect of n-3 and n-6 polyunsaturated fatty acids and their ethylesters on
      stimuli-dependent superoxide generation in neutrophils.
AB  - Polymorphonuclear leukocytes from healthy volunteers (HPMN) generated superoxide
      (O2*-) following treatment with various stimuli, such as phorbol myristate
      acetate (PMA), opsonized zymozan (OZ) and arachidonic acid (AA). Other types of n
      3 polyunsaturated fatty acids (PUFAS), such as docosahexaenoic acid (DHA),
      docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA), also stimulated O2*
      generation. The free form of DHA enhanced the generation of O2*- induced by PMA
      but inhibited that induced by OZ. In contrast, the ethylester of DHA (DHA-E)
      inhibited O2*- generation induced by PMA but stimulated that induced by OZ.
      Similar effects were also observed with ethylesters of EPA (EPA-E), DPA (DPA-E)
      and AA (AA-E). High concentrations of DHA-E reduced the PMA-induced formation of
      superoxide without affecting the cellular activity of protein kinase C (PKC).
      Similar phenomena were also observed with oral neutrophils from healthy
      volunteers (OPMN). These results indicate that PUFAS and their esters affect 02*-
      generation in human PMN via different pathways, thereby modulating inflammatory
      reactions.

PMID- 12002687
TI  - Basic study on radon effects and thermal effects on humans in radon therapy.
AB  - Because most of the diseases to which radon (222Rn) therapy is applied are
      related to activated oxygen, in this study the effect of the radioactivity of
      radon and the thermal effect were compared under a room or a hot spring condition
      with the same chemical component using as the parameters the activity of
      superoxide dismutase (SOD), which is an oxidation inhibitor, and lipid peroxide
      and low density lipoprotein (LDL)-cholesterol, which are closely involved in
      arteriosclerosis. Results show that the SOD activity was significantly increased,
      and the lipid peroxide and LDL-cholesterol levels were significantly decreased on
      days 6 and 7 of study. The results were about 2-fold larger in the radon group
      than in the thermo group. This suggests that the anti-oxidation function was more
      enhanced by radon therapy than by thermo therapy, and suggests that radon therapy
      may help to prevent the causes of life style-related diseases such as
      arteriosclerosis. These findings are important in understanding the mechanism of
      diseases in which radon therapy is used as treatment, and most of which are
      called activated oxygen-related diseases.

PMID- 12002688
TI  - Effect of urea denaturation on tryptophan fluorescence and nucleotide binding on
      tubulin studied by fluorescence and NMR spectroscopic methods.
AB  - Tubulin, the major protein of microtubules, has been shown to be an example of
      protein undergoing multistep unfolding. Local unfolding and stepwise loss of a
      number of characteristic functions were demonstrated. In order to understand urea
      induced effects on tryptophan fluorescence and nucleotide binding on tubulin,
      both fluorescence and NMR techniques were used. Tubulin was denatured by
      different urea concentrations. The present experiments were carried out at
      concentrations of tubulin (to approximately 10 microM) at which most of the
      protein will be in the dimeric state. Quenching studies in the presence of KI
      suggest that all the tryptophans are fairly solvent exposed. Similar studies
      using acrylamide as quencher, suggest unfolding of tubulin at these protein
      concentrations to be an apparent two state process between the native and the
      completely unfolded states unlike at low concentrations where a partially folded
      intermediate was observed. No observable effects of the nucleotide or the metal
      ion on tryptophan fluorescence were observed. An attempt was made using NMR to
      monitor the changes in the nucleotide interaction with tubulin as the protein is
      unfolded by urea denaturation. No significant effects were observed in the
      binding of the nucleotide to tubulin by urea denaturation.

PMID- 12002689
TI  - Interaction of microtubules with active principles of Xanthium strumarium.
AB  - Indigenous variety of Xanthium strumarium (X. strumarium) was screened for its
      antimitotic activity using the microtubule-tubulin system isolated from mammalian
      tissue. A preliminary phytochemical screening of the whole extracts of the plant
      was carried out followed by partial purification of the whole extract of
      X.strumarium. The separated fractions obtained were identified and used for in
      vitro polymerization studies. The whole as well as partially separated chemical
      constituents of X. strumarium showed effective inhibition of tubulin
      polymerization. The results thus suggest that X. strumarium may possess
      antimitotic components.

PMID- 12002690
TI  - Solution conformation of a rationally designed nonapeptide.
AB  - Partial 'turn-helix' type modules comprised of LD and DL chiral beta-turns
      serving as potential helix nucleators have been connected with a view to
      designing a nascent 'helix-turn-helix' type structure. Conformation of the
      resultant peptide Boc-(D)Glu-Ala-Aib-Lys-Val-Pro-(D)Asp-Leu-Leu-NHMe has been
      described in both DMSO and water.

PMID- 12002691
TI  - Learning and navigation of hornets: role of the various light perceiving organs.
AB  - The present study reports on experiments carried out on workers of Vespa
      orientalis (Hymenoptera, Vespinae). The experiments involved: learning of the
      workers upon their breeding box, evaluation of their ability to navigate back to
      the breeding box from ever increasing distances, and the effect which masking the
      various light perceiving organs has on the homing flight of hornets. The test
      hornets were removed from their breeding box to which they became accustomed and
      then released at gradually increasing distances from it (100 to 1000 meters) so
      as to assess their ability to return home. The group of hornets returning from a
      given distance was on the next day released at a greater distance, and so forth,
      and their homing capability was then compared between regular control groups and
      hornets that were coated with masking paint in various light-perceiving regions
      such as the clypeus, frons, ocelli and ommatidia on the head or segments 3 or 4
      of the gaster, the whole gaster or various combinations of the two (head and
      gaster). It was found that in all the groups combined (test + various controls)
      only about 44% of hornets released at a distance of 100 meters from the breeding
      box, found their way home. The percentage of homing hornets diminished with
      increasing distance from home and generally they responded in accordance with the
      formula: S(d)=exp(dp/beta), where d=distance; S(d)=the proportion of hornets
      expected to return from d; P=the shape parameter of the distribution: beta=the
      'scale' parameter of the distribution. Percentage of successfully homing hornets
      was significantly larger in control hornets than in treated ones only at a
      release distance of 1000 meters.

PMID- 12002692
TI  - Navigation and thermophotovoltaic activity by hornets at different light
      conditions: the influence of UVB blockers.
AB  - The aim of the present investigation was two-fold: a) to observe the homing of
      the Oriental hornet, Vespa orientalis (Hymenoptera, Vespinae) from different
      distances; and b) to study the photothermoelectric activity of hornet cuticle
      obtained from the subjects of goal (a) and kept frozen for a number of days prior
      to its testing. In both the above mentioned phases of the investigation, an
      attempt was made to assess how the covering of the hornets' cuticle with Ultra
      Violet B (UVB) blockers affects their activity as compared to the control. Flying
      hornets were observed to return to the nest from distances of up to 7 km, once
      they had learned the way back. However, covering of the cuticle with UVB blockers
      increases the percentage of 'non-returners' to nearly 100%. Covering the cuticle
      completely or partly with a number of UVB blockers (except for Sisley) proves
      lethal for the hornets within 24 hours. A statistical model on homing is proposed
      of the effect of range, of covering with UVB blockers and covering ocelli with
      Tippex. In the wing of the hornet there is increase in the electric current with
      rise in the temperature and decrease in the current upon drop of the temperature,
      but light has no effect on this alar (wing) current. Contrariwise, the body
      cuticle of the hornet responds to both temperature and illumination in terms of
      its electric current. Coating of the cuticle with UVB blockers causes in the wing
      (under all conditions of illumination) and in the cuticle (only in the dark) a
      moderation in the amplitude of the photothermoelectric current.

PMID- 12002693
TI  - Oxidative burst and 1H-NMR-detectable mobile lipids in neutrophils.
AB  - Neutrophils exposed to pro-inflammatory substances have an increased capability
      to respond to a membrane receptor-binding stimulus triggering an oxidative burst.
      One other considered sign of neutrophil activation is the appearance of a high
      resolution 'H-NMR spectrum probably resulting from a rearrangement of neutral
      lipids in the membrane. The relationship between these two events is here
      studied. Neutrophils were recovered from a subcutaneous fungal infection using
      two murine lineages that respond differently to infection. It was concluded that
      rearrangement of lipids in the membrane, observable by NMR, appears also in
      neutrophils that do not exhibit the classical sign of activation, that is the
      increased expression of membrane receptors.

PMID- 12002694
TI  - How to explain established relationships between ion fluxes across cell membranes
      and Na,K-ATPase activities under the assumption that the Na,K-ATPase is no ion
      pump.

PMID- 12002695
TI  - Race and self-esteem: meta-analyses comparing whites, blacks, Hispanics, Asians,
      and American Indians and comment on Gray-Little and Hafdahl (2000).
AB  - These meta-analyses examine race differences in self-esteem among 712 datapoints.
      Blacks scored higher than Whites on self-esteem measures (d = 0.19), but Whites
      scored higher than other racial minority groups, including Hispanics (d = -0.09),
      Asians (d = -0.30), and American Indians (d = -0.21). Most of these differences
      were smallest in childhood and grew larger with age. Blacks' self-esteem
      increased over time relative to Whites', with the Black advantage not appearing
      until the 1980s. Black and Hispanic samples scored higher on measures without an
      academic self-esteem subscale. Relative to Whites, minority males had lower self
      esteem than did minority females, and Black and Hispanic self-esteem was higher
      in groups with high socioeconomic status. The results are most consistent with a
      cultural interpretation of racial differences in self-esteem.

PMID- 12002696
TI  - Naive causal understanding of valenced behaviors and its implications for social
      information processing.
AB  - People bring to bear on their understanding of others' behaviors naive theories
      of the causes of valenced behaviors. Generally, positive behaviors are understood
      to be caused by social demands, whereas negative behaviors are understood to be
      caused by people's dispositions. Various research findings are reviewed in
      support of the idea that people possess such naive theories. The analysis is
      extended to establish how these sense-making tendencies affect the manner in
      which people approach and process information about others. A second set of
      studies is reviewed in support of these implications for person perception.
      Comparisons to other models of social inference are considered, implications of
      the frame-work are examined, and the framework is situated within a general model
      of the attribution process.

PMID- 12002697
TI  - The interplay of meaning, sound, and syntax in sentence production.
AB  - A discussion of modularity in language production processes, with special
      emphasis on processes for retrieving words and building syntactic structures for
      a to-be-uttered sentence, is presented. The authors' 1st goal was to assess the
      extent to which information processing is encapsulated between different
      processing stages. In particular, they assessed whether the input from one
      processing stage to the next is minimal and whether the flow of information in
      the system is strictly unidirectional. On the basis of the reviewed evidence,
      they conclude that both assumptions have to be revised. Their 2nd goal was to
      propose an altemative framework that does not assume strict encapsulation but
      that maintains multiple levels of integration for production.

PMID- 12002698
TI  - Are animals stuck in time?
AB  - People can time travel cognitively because they can remember events having
      occurred at particular times in the past (episodic memory) and because they can
      anticipate new events occurring at particular times in the future. The ability to
      assign points in time to events arises from human development of a sense of time
      and its accompanying time-keeping technology. The hypothesis is advanced that
      animals are cognitively stuck in time: that is, they have no sense of time and
      thus have no episodic memory or ability to anticipate long-range future events.
      Research on animals' abilities to detect time of day, track short time intervals,
      remember the order of a sequence of events, and anticipate future events are
      considered, and it is concluded that the stuck-in-time hypothesis is largely
      supported by the current evidence.

PMID- 12002699
TI  - Genetic and environmental influences on antisocial behavior: a meta-analysis of
      twin and adoption studies.
AB  - A meta-analysis of 51 twin and adoption studies was conducted to estimate the
      magnitude of genetic and environmental influences on antisocial behavior. The
      best fitting model included moderate proportions of variance due to additive
      genetic influences (.32), nonadditive genetic influences (.09), shared
      environmental influences (.16), and nonshared environmental influences (.43). The
      magnitude of familial influences (i.e., both genetic and shared environmental
      influences) was lower in parent-offspring adoption studies than in both twin
      studies and sibling adoption studies. Operationalization, assessment method,
      zygosity determination method, and age were significant moderators of the
      magnitude of genetic and environmental influences on antisocial behavior, but
      there were no significant differences in the magnitude of genetic and
      environmental influences for males and females.

PMID- 12002700
TI  - In between lakes.

PMID- 12002701
TI  - Evaluation of MS-209, a novel multidrug-resistance-reversing agent, in tumour
      bearing mice by technetium-99m-MIBI imaging.
AB  - MS-209 is a newly synthesised multidrug-resistance (MDR)-reversing agent with few
      side-effects. In this study, we evaluated the effect of MS-209 on P-glycoprotein
      (Pgp)-positive tumours in mice by means of technetium-99m
      methoxyisobutylisonitrile (MIBI) imaging. Mice received Pgp-negative KB-3-1 or
      Pgp-positive KB-C1 cell xenografts. KB-3-1-bearing mice were administered 0 or
      100 mg/kg of MS-209 (groups S0 and S100, respectively), and KB-C1-bearing mice 0,
      50, 100 or 200 mg/kg (groups R0, R50, R100 and R200, respectively), 30 min before
      imaging studies. Dynamic 99mTc-MIBI images were acquired for 30 min, followed by
      biodistribution studies. Washout of 99mTc-MIBI from the tumours was faster in
      group R0 than in group S0 on visual analysis, and the washout half-time estimated
      by region of interest analysis was shorter in group R0 than in group S0.
      Biodistribution studies revealed that 99mTc-MIBI accumulation in tumours
      (expressed as %ID/g) was also lower in group R0 than in group S0. MS-209 delayed
      the 99mTc-MIBI washout from KB-C1 tumours. Washout half-time was longer in groups
      R50, R100 and R200 than in group R0. A higher %ID/g was observed in groups R100
      and R200 than in group R0. In KB-3-1 tumours, MS-209 had no effect on the washout
      half-time or the %ID/g. This study demonstrated that MS-209 increases the 99mTc
      MIBI accumulation in Pgp-positive tumours. The MDR-reversing effect of MS-209
      could be effectively evaluated with 99mTc-MIBI visually and non-invasively in
      vivo. 99mTc-MIBI imaging with MS-209 prior to chemotherapy should contribute
      significantly to the treatment strategy in patients with multidrug-resistant
      tumours.

PMID- 12002702
TI  - Quantification of beta-adrenoceptor density in the human heart with (S)-[11C]CGP
      12388 and a tracer kinetic model.
AB  - The aim of this study was to determine whether the beta-adrenoceptor receptor
      density (Bmax) and the ligand affinity (KD) of (S)-[11C]CGP 12388 for the beta
      adrenoceptor receptor could be determined using full tracer kinetic modelling of
      the transport of the ligand and its interaction with the receptor. This approach
      minimises the a priori assumptions and may thus serve as a gold standard to
      validate other simplified methods. Dynamic positron emission tomography (PET)
      data were acquired in six healthy subjects during 60 min. Three different
      injection protocols were applied, each consisting of three injections with
      varying SAs: high specific activity (SA), low SA or unlabelled ligand only.
      Arterial blood samples were collected via a cannula in the radial artery. Time
      activity data in myocardial tissue were obtained using regions of interest (ROIs)
      on short-axis planes. All data were analysed with a two-tissue compartment, six
      parameter (K1, k2, k(on), k(off), Bmax, F(bv)) model that relies on explicit
      compartments for describing the kinetics of both labelled and unlabelled
      radioligand. Time-activity curves showed that unlabelled ligand could displace
      the radioligand from the receptor. This resulted in increased radioactivity
      levels in plasma. Modelling results yielded Bmax values of 9.74+/-1.80 nM and a
      KD of 0.58+/-0.22 nM, assuming a reaction volume of 0.15. In addition, parametric
      polar images of Bmax could be calculated. The protocol with injections of high
      SA, low SA, and unlabelled ligand, respectively, was found to be the most
      sensitive to parameter changes. We conclude that with tracer kinetic modelling of
      (S)-[11C]CGP 12388, the beta-adrenoceptor density in the human heart can
      accurately be obtained in vivo. This approach may thus serve as a gold standard.

PMID- 12002703
TI  - The hidden sentinel node in breast cancer.
AB  - The purpose of this study was to analyse the occurrence of non-visualisation
      during preoperative lymphoscintigraphy for sentinel node identification in breast
      cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node
      negative breast cancer patients (501 sentinel node procedures) after injection of
      technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar
      images were obtained a few minutes and 4 h after injection. The sentinel node was
      intraoperatively identified with the aid of patent blue dye and a gamma-ray
      detection probe. A sentinel node was visualised on the 4-h images in 449 of 501
      procedures (90%). This visualisation rate improved from 76% to 94% during the
      study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed
      to show, resulted in visualisation in four of them. A repeat injection of
      radiocolloid in 11 patients revealed a sentinel node in six. In the end, the
      visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of
      the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were
      visualised were tumour-positive in 38% and non-visualised sentinel nodes were
      involved in 50% (chi2, P=0.17). In a multivariate regression analysis,
      scintigraphic non-visualisation was independently associated with increased
      patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of
      tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of
      radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast
      cancer, especially in elderly women. Delayed imaging and re-injection of the
      radioactive tracer increase the visualisation rate. The non-visualised sentinel
      node can be identified intraoperatively in more than half of the patients.

PMID- 12002704
TI  - ACE inhibition is superior to angiotensin receptor blockade for renography in
      renal artery stenosis.
AB  - Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor
      antagonists are able to prevent the vasoconstrictive effect of angiotensin II on
      the efferent renal vessels, which is believed to play an important role in
      renovascular hypertension. This effect is assumed to be essential for the
      demonstration of renovascular hypertension by captopril renography. In this
      study, renographic changes induced by captopril and the AT1 receptor antagonist
      valsartan were compared in patients with a high probability for renovascular
      hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of
      stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline
      renography were performed within 48 h using technetium-99m
      mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin
      concentration before and after intervention was determined and urinary flow was
      estimated from the urinary output of the hydrated patients. Alterations in
      renographic curves after intervention were evaluated according to the Santa Fe
      consensus on ACE inhibitor renography. Captopril renography was positive,
      indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas
      valsartan renography was positive in only ten. Blood pressure during captopril
      and valsartan renography was not different; reduction in blood pressure was the
      same after valsartan and captopril. Plasma renin concentration was comparable for
      valsartan and captopril studies, showing suppressed values after intervention in
      as many as 12 of the 25 patients. Urinary flow after valsartan was higher than
      after captopril (P<0.05). However, this difference could not explain the markedly
      higher sensitivity of captopril compared with valsartan in demonstrating renal
      artery stenosis. In 14 of the 25 patients, blood pressure response to
      revascularisation was monitored, showing a much better predictive value for
      captopril renography. It is concluded that captopril renography is much more
      sensitive than valsartan renography in detecting a clinically significant renal
      artery stenosis. Furthermore, our data suggest that other effects, such as that
      on the prostaglandin-bradykinin system, are of at least similar importance to ACE
      inhibition for the high diagnostic sensitivity of captopril renography regarding
      renovascular hypertension.

PMID- 12002705
TI  - A femoral arteriovenous shunt facilitates arterial whole blood sampling in
      animals.
AB  - In this study we evaluated on-line continuous blood sampling in a femoral
      arteriovenous (a-v) shunt for use in quantitative tracer studies using gamma
      emitting radionuclides in animals. The shunt consisted of 40 cm polyethylene
      tubing (PE-50) guided through a coincidence probe. Two three-way valves allowed
      blood pressure measurements and tracer injection. Blood flow in the shunt and the
      impulse response function (IRF) were assessed using heparinized human blood mixed
      with fluorine-18 fluorodeoxyglucose (FDG). In vivo experiments were performed in
      eight male rats (300-350 g) anaesthetized with halothane. In three rats, manual
      blood sampling was performed in parallel with on-line sampling. In another five
      animals, the arterial whole blood activity was recorded on-line for 40 min. For
      the experiments 150-180 MBq FDG was injected over 35 s. Blood flow in the shunt
      was 23.6, 29.2 and 42.8 ml/h at 100, 120 and 160 mmHg, respectively. The IRF was
      characterized by minimal dispersion (1-2 s FWHM). Deconvolution of the measured
      arterial input curves with the IRF changed the measured curve only minimally.
      Whole blood radioactivity concentration derived from manual and on-line sampling
      were in excellent agreement. The curves derived from on-line sampling were of
      high statistical quality. In conclusion, a femoral a-v shunt allows multiple
      manipulations such as measurement of the arterial whole blood activity,
      continuous blood pressure monitoring, injection of the tracer and collection of
      blood samples if necessary. It is not associated with blood loss if the
      collection of blood samples is not required. It is more convenient to use than
      manual sampling, the peak of the input curve is never missed and the input curves
      are of high statistical quality.

PMID- 12002706
TI  - Pretreatment evaluation of carcinomas of the hypopharynx and larynx with 18F
      fluorodeoxyglucose, 123I-alpha-methyl-L-tyrosine and 99mTc-hexakis-2
      methoxyisobutylisonitrile.
AB  - While fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography
      (PET) is helpful in the pretherapeutic evaluation of head and neck cancer, it is
      only available in selected centres. Therefore, single-photon emission tomography
      (SPET) tracers would be desirable if they were to demonstrate tumour uptake
      reliably. This multitracer study was performed to evaluate the pretherapeutic
      uptake of the SPET tracers iodine-123 alpha-methyl-L-tyrosine (IMT) and
      technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) in primary
      carcinomas of the hypopharynx and larynx and to compare the results with those of
      FDG PET. We examined 22 fasted patients (20 male, 2 female, mean age 60.5+/-10.2
      years) with histologically confirmed carcinoma of the hypopharynx (n=9) or larynx
      (n=13), within 1 week before therapy. In 20 patients a cervical PET scan was
      acquired after intravenous injection of 232+/-43 MBq 18F-FDG. Data analysis was
      semiquantitative, being based on standardised uptake values (SUVs) obtained at 60
      90 min after injection. After injection of 570+/-44 MBq 99mTc-MIBI, cervical SPET
      scans (high-resolution collimator, 64x64 matrix, 64 steps, 40 s each) were
      obtained in 19 patients, 15 and 60 min after tracer injection. Finally, 15 min
      after injection of 327+/-93 MBq 123I-IMT (medium-energy collimator, 64x64 matrix,
      64 steps, 40 s each) SPET scans were acquired in 15 patients. All images were
      analysed visually and by calculating the tumour to nuchal muscle ratio. Eighteen
      of 20 (90%) carcinomas showed an increased glucose metabolism, with a mean SUV of
      8.7 and a mean carcinoma to muscle ratio of 7.3. The IMT uptake was increased in
      13 of 15 (87%) patients, who had a mean carcinoma to muscle ratio of 2.9. Only 13
      of 19 (68%) carcinomas revealed pathological MIBI uptake, with a mean tumour to
      muscle ratio of 2.2 and no significant difference between early and late MIBI
      SPET images (P=0.23). In conclusion, in the diagnosis of primary carcinomas of
      the hypopharynx and larynx, IMT SPET achieved a detection rate comparable to that
      of FDG PET. IMT SPET was clearly superior to MIBI SPET in this population. A
      further evaluation of the specificity of IMT in a larger number of patients
      appears justified.

PMID- 12002707
TI  - Usefulness of a three-dimensional stereotaxic ROI template on anatomically
      standardised 99mTc-ECD SPET.
AB  - We have constructed a three-dimensional stereotaxic ROI template (3DSRT) on
      anatomically standardised cerebral blood flow (CBF) single-photon emission
      tomography (SPET) images to objectively estimate regional CBF (rCBF). The 3DSRT
      is composed of 259 regions of interest (ROIs) in 11 segments (1, superior
      frontal; 2, middle and inferior frontal; 3, primary sensorimotor; 4, parietal; 5,
      angular; 6, temporal; 7, occipital; 8, pericallosal; 9, lenticular nucleus; 10,
      thalamus; 11, hippocampus) on each side. We measured the rCBF values of the 518
      ROIs and calculated the area-weighted average (segmental CBF; sCBF) of the 22
      segments based on the rCBF in each ROI. We compared vascular reserve before and
      after revascularisation surgery using sCBF on anatomically standardised resting
      and acetazolamide (Acz)-challenged CBF SPET images, which were obtained using an
      equal-volume-split dual-injection single-day protocol [resting and vascular
      reserve (RVR) method] in 13 patients who had not suffered any major stroke but
      did have significant cerebrovascular stenosis. Prior to the evaluation, we
      examined the sCBF values of 16 subjects with various cerebrovascular conditions
      (8, normal; 3, lacunar infarction; 2, chronic infarction; 2, meningioma; 1,
      aneurysm) using physiological saline instead of Acz (placebo study) in order to
      confirm the reproducibility of the RVR method. In the placebo study we observed
      excellent linearity (y=1.444+0.964x) between the 352 pairs of baseline (x) and
      post-placebo (y) sCBF values in the 16 subjects, irrespective of the segment
      location. In all of the 13 patients, estimation of sCBF demonstrated impaired
      vascular reserve pre-operatively and improved vascular reserve postoperatively.
      We conclude that the 3DSRT, which could be identically set on the anatomically
      standardised images obtained at baseline and after Acz injection, allowed
      objective assessment of the pre- and postoperative vascular reserve, which was
      not easy with conventional ROI settings. While 3DSRT appeared useful for the
      evaluation of regional vascular reserve as well as rCBF, further study is
      necessary to clarify its general clinical value.

PMID- 12002708
TI  - The effect of scatter correction on 123I-IMP brain perfusion SPET with the triple
      energy window method in normal subjects using SPM analysis.
AB  - Scatter correction (SC) using the triple energy window method (TEW) has recently
      been applied for brain perfusion single-photon emission tomography (SPET). The
      aim of this study was to investigate the effect of scatter correction using TEW
      on N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPET in normal subjects. The
      study population consisted of 15 right-handed normal subjects. SPET data were
      acquired from 20 min to 40 min after the injection of 167 MBq of IMP, using a
      triple-head gamma camera. Images were reconstructed with and without SC. 3D T1
      weighted magnetic resonance (MR) images were also obtained with a 1.5-Tesla
      scanner. First, IMP images with and without SC were co-registered to the 3D MRI.
      Second, the two co-registered IMP images were normalised using SPM96. A t
      statistic image for the contrast condition effect was constructed. We
      investigated areas using a voxel-level threshold of 0.001, with a corrected
      threshold of 0.05. Compared with results obtained without SC, the IMP
      distribution with SC was significantly decreased in the peripheral areas of the
      cerebellum, the cortex and the ventricle, and also in the lateral occipital
      cortex and the base of the temporal lobe. On the other hand, the IMP distribution
      with SC was significantly increased in the anterior and posterior cingulate
      cortex, the insular cortex and the medial part of the thalamus. It is concluded
      that differences in the IMP distribution with and without SC exist not only in
      the peripheral areas of the cerebellum, the cortex and the ventricle but also in
      the occipital lobe, the base of the temporal lobe, the insular cortex, the medial
      part of the thalamus, and the anterior and posterior cingulate cortex. This needs
      to be recognised for adequate interpretation of IMP brain perfusion SPET after
      scatter correction.

PMID- 12002709
TI  - CT vs 68Ge attenuation correction in a combined PET/CT system: evaluation of the
      effect of lowering the CT tube current.
AB  - With the introduction of combined positron emission tomography/computed
      tomography (PET/CT) systems, several questions have to be answered. In this work
      we addressed two of these questions: (a) to what value can the CT tube current be
      reduced while still yielding adequate maps for the attenuation correction of PET
      emission scans and (b) how do quantified uptake values in tumours derived from CT
      and germanium-68 attenuation correction compare. In 26 tumour patients,
      multidetector CT scans were acquired with 10, 40, 80 and 120 mA (CT10, CT40, CT80
      and CT120) and used for the attenuation correction of a single FDG PET emission
      scan, yielding four PET scans designated PET(CT10)-PET(CT120). In 60 tumorous
      lesions, FDG uptake and lesion size were quantified on PET(CT10)-PET(CT120). In
      another group of 18 patients, one CT scan acquired with 80 mA and a standard
      transmission scan acquired using 68Ge sources were employed for the attenuation
      correction of the FDG emission scan (PET(CT80), PET(68Ge)). Uptake values and
      lesion size in 26 lesions were compared on PET(CT80) and PET(68Ge). In the first
      group of patients, analysis of variance revealed no significant effect of CT
      current on tumour FDG uptake or lesion size. In the second group, tumour FDG
      uptake was slightly higher using CT compared with 68Ge attenuation correction,
      especially in lesions with high FDG uptake. Lesion size was similar on PET(CT80)
      and PET(68Ge). In conclusion, low CT currents yield adequate maps for the
      attenuation correction of PET emission scans. Although the discrepancy between CT
      and 68Ge-derived uptake values is probably not relevant in most cases, it should
      be kept in mind if standardised uptake values derived from CT and 68Ge
      attenuation correction are compared.

PMID- 12002710
TI  - PET-CT image co-registration in the thorax: influence of respiration.
AB  - Because anatomical information on fluorine-18 fluorodeoxyglucose (FDG) whole-body
      positron emission tomography (PET) images is limited, combination with structural
      imaging is often important. In principle, software co-registration of PET and
      computed tomography (CT) data or dual-modality imaging using a combined PET-CT
      camera has an important role to play, since "hardware-co-registered" images are
      thereby made available. A major unanswered question is under which breathing
      protocol the respiration level in the CT images of a patient will best match the
      PET images, which represent summed images over many breathing cycles. To address
      this issue, 28 tumour patients undergoing routine FDG PET examinations were
      included in this study. In ten patients, PET and CT were performed using a new
      combined high-performance in-line PET-CT camera without the need for
      repositioning of the patient, while in 18 patients imaging was performed on
      separate scanners located close to each other. CT was performed at four
      respiration levels: free breathing (FB), maximal inspiration (MaxInsp), maximal
      expiration (MaxExp) and normal expiration (NormExp). The following distances were
      measured: (a) between a reference point taken to be the anterior superior edge of
      intervertebral disc space T10-11 and the apex of the lung, (b) from the apex of
      the lung to the top of the diaphragm, (c) from the apex of the lung to the costo
      diaphragmatic recess and (d) from the reference point to the lateral thoracic
      wall. Differences between CT and corresponding PET images in respect of these
      distances were compared. In addition, for each of 15 lung tumours in 12 patients,
      changes in tumour position between PET and CT using the same protocol were
      measured. CT during NormExp showed the best fit with PET, followed by CT during
      FB. The mean differences in movement of the diaphragmatic dome on CT during
      NormExp, FB, MaxInsp and MaxExp, as compared with its level on PET scan, were,
      respectively, 0.4 mm (SD 11.7), -11.6 mm (13.3), -44.4 mm (25.5) and -9.5 mm
      (25.6). CT acquired in MaxExp and MaxInsp is not suitable for image co
      registration owing to the poor match of images in MaxInsp and because of
      difficulties with patient performance in MaxExp. With reference to lung lesions,
      NormExp showed the best results, with a higher probability of a good match and a
      smaller range of measured values in comparison with FB. Image misregistration in
      combined PET-CT imaging can be minimized to dimensions comparable to the spatial
      resolution of modern PET scanners. For PET-CT image co-registration, the use of a
      normal expiration breath-hold protocol for CT acquisition is recommended,
      independent of whether combined PET-CT systems or stand-alone systems are used.

PMID- 12002711
TI  - Initial results in the assessment of multiple myeloma using 18F-FDG PET.
AB  - This prospective study was undertaken to investigate the appearance of multiple
      myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET).
      Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its
      influence on patient management were evaluated. Forty-three patients with known
      multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The
      results of routinely performed radiographs and of scans obtained using all
      available imaging modalities (MRI, CT), as well as the clinical course, were used
      for verification of detected lesions. Focally increased tracer uptake was
      observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23
      patients. In addition, 71 further bone lesions which were negative on radiographs
      were detected in 14 patients. Twenty-six (36.6%) of these lesions could be
      confirmed in ten patients. As a result of FDG-PET imaging, clinical management
      was influenced in five (14.0%) patients. The positive predictive value for active
      disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG
      uptake and 75% in patients with diffuse bone marrow uptake. Depending on the
      interpretation of the PET scans in patients with diffuse bone marrow uptake, the
      sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%.
      FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a
      greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients
      who had osteolytic bone lesions. FDG-PET might contribute to the initial staging
      of solitary plasmacytoma.

PMID- 12002712
TI  - Head and neck imaging with PET and PET/CT: artefacts from dental metallic
      implants.
AB  - Germanium-68 based attenuation correction (PET(Ge68)) is performed in positron
      emission tomography (PET) imaging for quantitative measurements. With the recent
      introduction of combined in-line PET/CT scanners, CT data can be used for
      attenuation correction. Since dental implants can cause artefacts in CT images,
      CT-based attenuation correction (PET(CT)) may induce artefacts in PET images. The
      purpose of this study was to evaluate the influence of dental metallic artwork on
      the quality of PET images by comparing non-corrected images and images
      attenuation corrected by PET(Ge68) and PET(CT). Imaging was performed on a novel
      in-line PET/CT system using a 40-mAs scan for PET(CT) in 41 consecutive patients
      with high suspicion of malignant or inflammatory disease. In 17 patients,
      additional PET(Ge68) images were acquired in the same imaging session. Visual
      analysis of fluorine-18 fluorodeoxyglucose (FDG) distribution in several regions
      of the head and neck was scored on a 4-point scale in comparison with normal grey
      matter of the brain in the corresponding PET images. In addition, artefacts
      adjacent to dental metallic artwork were evaluated. A significant difference in
      image quality scoring was found only for the lips and the tip of the nose, which
      appeared darker on non-corrected than on corrected PET images. In 33 patients,
      artefacts were seen on CT, and in 28 of these patients, artefacts were also seen
      on PET imaging. In eight patients without implants, artefacts were seen neither
      on CT nor on PET images. Direct comparison of PET(Ge68) and PET(CT) images showed
      a different appearance of artefacts in 3 of 17 patients. Malignant lesions were
      equally well visible using both transmission correction methods. Dental implants,
      non-removable bridgework etc. can cause artefacts in attenuation-corrected images
      using either a conventional 68Ge transmission source or the CT scan obtained with
      a combined PET/CT camera. We recommend that the non-attenuation-corrected PET
      images also be evaluated in patients undergoing PET of the head and neck.

PMID- 12002713
TI  - Clinical features and gallium scan in the detection of post-surgical infection in
      the elderly.
AB  - Common signs of infection, such as an elevated level of C-reactive protein (CRP),
      raised white blood cell (WBC) count and increased temperature, may not be present
      in elderly patients when infection occurs. In addition, these typical signs may
      be normal events during the postoperative period. Therefore, early detection of
      post-surgical infection may be difficult in the elderly population. In this
      study, we evaluated the usefulness of gallium scan in the detection of infection
      in elderly patients after colorectal surgery and compared it with CRP, WBC count
      and ear temperature (ET) examinations. Thirty-three patients undergoing
      colorectal surgery and aged over 60 years were enrolled in the study. All
      patients underwent a gallium scan and CRP, WBC and ET examinations. Of the 33
      patients, 18 (54.5%) were diagnosed with infection. The diagnostic sensitivity
      was 100% for both gallium scan and the CRP test, but only 44.4% and 61.1% for the
      WBC count and ET, respectively. The diagnostic specificity of the gallium scan,
      WBC count and ET was 80% or more, whereas that of the CRP test was only 53.3%.
      The diagnostic accuracy of gallium scan, CRP test, WBC count and ET was 90.9%,
      78.8%, 60.6% and 72.7%, respectively. In conclusion, both WBC and ET examinations
      show low sensitivity in the detection of infection in the elderly population
      after colorectal surgery. The CRP test has good sensitivity but low specificity.
      Of the four diagnostic modalities, gallium scan had the highest overall
      diagnostic accuracy (90.9%) while the WBC test had the lowest (60.6%).

PMID- 12002714
TI  - 99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic
      polyneuropathy.
AB  - Familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin
      (ATTR) mutations is the most common form of hereditary amyloidosis. We
      investigated the diagnostic value of the bone scanning agent technetium-99m 3,3
      diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in this disease. Eight
      patients (four males, four females; age 54.4+/-8.3 years, range 43-67 years) with
      ATTR-FAP proven by immunohistochemistry and molecular analysis and a control
      group comprising ten oncological out-patients (five males, five females; age
      53.4+/-8.5 years, range 34-66 years) without evidence of bony metastases were
      studied using 99mTc-DPD. Whole body tracer retention was 80.1%+/-10.3% (range
      65.1%-94.8%) in FAP patients and 55.7%+/-8.1% (range 40.2%-66.7%) in controls at
      3 h p.i. (P<0.001), and cardiac uptake was 7.3%+/-2.2% (range 4.2%-10.1%) in FAP
      patients and 3.1%+/-0.5% (range 2.3%-4.0%) in controls (P<0.001). The heart/whole
      body uptake ratio was 8.9%+/-1.7% (range 6.5%-11.0%) in FAP patients and 5.6%+/
      0.5% (range 5.1%-6.8%) in controls (P<0.001). The three FAP patients with the
      highest cardiac tracer uptake had cardiomyopathy or arrhythmia. 99mTc-DPD
      scintigraphy is proposed as a simple and valuable diagnostic aid to evaluate the
      severity of the disease and the risk of concomitant heart problems.

PMID- 12002715
TI  - Gallium-67 scintigraphy in lymphoma: is there a benefit of image fusion with
      computed tomography?
AB  - The usefulness and complementarity of gallium (67Ga) scintigraphy and computed
      tomography (CT) in the management of patients with lymphoma have been extensively
      demonstrated. Owing to a lack of anatomical landmarks and physiological
      distribution of the tracer, precise localisation of abnormalities on 67Ga
      scintigraphy can be difficult. As fusion imaging techniques between single-photon
      emission tomography (SPET) and CT have been developed recently, we investigated
      whether use of CT/67Ga SPET fusion imaging could help in the interpretation of
      67Ga scintigraphy. From November 1999 to May 2001, 52 consecutive fusion studies
      were performed in 38 patients [22 patients with Hodgkin's disease (HD) and 16
      patients with non-Hodgkin's lymphoma (NHL)] as part of pre-treatment staging
      (n=13), treatment evaluation (n=20) or evaluation of suspected recurrence (n=19).
      67Ga scintigraphy was carried out 2 and 6 days following the injection of 185-220
      MBq 67Ga citrate. On day 2, 67Ga SPET and CT were performed, focussing on the
      chest and/or the abdomen/pelvis. Data from each imaging method were co-registered
      using external markers. 67Ga scintigraphy and CT were initially interpreted
      independently by nuclear medicine physicians and radiologists. CT/67Ga SPET
      fusion studies were then jointly interpreted and both practitioners indicated
      when fusion provided additional information in comparison with CT and 67Ga SPET
      alone. Image fusion was considered to be of benefit in 12/52 (23%) studies which
      were performed for initial staging (n=4), treatment evaluation (n=4) or
      evaluation of suspected recurrence (n=4). In these cases, image fusion allowed
      either confirmation and/or localisation of pathological gallium uptake (n=10) or
      detection of lesions not visible on CT scan (n=2). Fusion was relevant for
      discrimination between osseous lesions and lymph node involvement adjacent to
      bone, especially in the thoracic and lumbar spine and pelvis. In the abdomen and
      pelvis, fusion helped to differentiate physiological bowel elimination from
      abnormal uptake, and assisted in precisely locating uptake in neighbouring
      viscera of the left hypochondrium, including the spleen, left liver lobe, coeliac
      area, stomach wall and even the splenic flexure. At the thoracic level, fusion
      also proved useful for demonstrating clearly the relationships of abnormal foci
      to the pleura, hepatic dome, mediastinum, ribs or thoracic spine. Clinical
      management was altered by fusion imaging in one patient (chemotherapy was given
      instead of radiotherapy) and was potentially affected in three other patients (in
      that, in conjunction with other factors, the results of fusion imaging had an
      influence on the decision regarding use of irradiation and especially the
      treatment volume). In conclusion, CT/67Ga SPET fusion imaging allowed precise
      localisation of gallium uptake and correct attribution to the involved viscera,
      thereby altering the diagnosis in 20%-25% of studies in comparison with CT and
      67Ga SPET analyses alone. CT/67Ga SPET fusion therefore appears valuable in
      facilitating the interpretation of 67Ga scintigraphy and we recommend its use in
      patients with lymphoma when CT and 67Ga scintigraphy are planned.

PMID- 12002716
TI  - The type 2 human somatostatin receptor as a platform for reporter gene imaging.
AB  - The human somatostatin receptor subtype 2A (hSSTr2) is under evaluation as a
      reporter gene for molecular imaging applications. Two approved somatostatin
      analogues are already available for imaging expression of the reporter gene
      following delivery with adenoviral (Ad) vectors or other genetic targeting
      strategies. In animal models, Ad-mediated expression of hSSTr2 in subcutaneous
      and intraperitoneal tumors was detected by non-invasive gamma camera imaging.
      This review discusses the rationale and strategy for using the hSSTr2 reporter
      gene as a platform for imaging applications.

PMID- 12002717
TI  - "Seeing inside the body": MR imaging of gene expression.
AB  - The goal of this review is to describe the developments and recent advances that
      are enabling applications of magnetic resonance (MR) imaging for non-invasive
      imaging of gene expression. Guiding application of this technology has been the
      need to test, in vivo and in real time, hypotheses developed in multiple
      scientific fields. Advances made in the human genome project and our increasing
      understanding of the molecular basis of normal and disease physiology have
      defined questions that will only be answered when specific molecular imaging
      modalities are developed. In this review we will briefly summarize the salient
      features of MR imaging to provide the backdrop for a more detailed discussion of
      specific applications of MR imaging of gene expression. We will conclude with the
      insights gained from genomic approaches and how they might be exploited for MR
      imaging of gene expression in the future.

PMID- 12002718
TI  - Should SPET attenuation correction be more widely employed in routine clinical
      practice? For.

PMID- 12002719
TI  - Should SPET attenuation correction be more widely employed in routine clinical
      practice? Against.
AB  - The development of reliable and accurate devices for the correction of nonuniform
      soft tissue attenuation is essential for the future clinical use of SPET
      myocardial perfusion imaging. In addition to abolishing false-positive defects,
      which is the chief goal, such corrected SPET images may allow for improved
      detection of coronary artery disease and perhaps ultimately for true
      quantification of regional myocardial blood flow. Although progress has been
      made, most existing attenuation correction devices are not yet ready for prime
      time. To date the literature shows as many positive results as negative results.
      There is considerable uncertainty, confusion, and skepticism about the true
      reliability and value of currently available attenuation correction packages.
      Although commonly referred to as "attenuation correction devices," these packages
      are in fact much more complex systems and contain novel mechanical designs, novel
      image acquisition and image reconstruction algorithms, scatter correction, and
      depth-dependent resolution compensation, in addition to attenuation correction.
      Each of these variables needs to be better understood and tested prior to
      clinical implementation. Although the general concepts are shared, there are as
      may different approaches to attenuation correction as there are vendors. In order
      to minimize the confusion of potential buyers about such complex systems, it is
      desirable that, before attenuation correction is implemented in routine clinical
      practice, each attenuation correction device is rigorously tested using a
      standardized testing protocol. Potential buyers of equipment should be able to
      compare the results of testing with various devices against predefined criteria
      in order to make an educated decision. Such standards have as yet not been
      developed. At the present time it is unclear whether attenuation correction of
      cardiac SPET will remain the emperor's new clothes or will develop into a
      fashionable Armani suit. Until further progress has been made, one cannot
      recommend attenuation correction devices for routine clinical practice.

PMID- 12002720
TI  - PET and SPET tracers for mapping the cardiac nervous system.
AB  - The human cardiac nervous system consists of a sympathetic and a parasympathetic
      branch with (-)-norepinephrine and acetylcholine as the respective endogenous
      neurotransmitters. Dysfunction of the cardiac nervous system is implicated in
      various types of cardiac disease, such as heart failure, myocardial infarction
      and diabetic autonomic neuropathy. In vivo assessment of the distribution and
      function of cardiac sympathetic and parasympathetic neurones with positron
      emission tomography (PET) and single-photon emission tomography (SPET) can be
      achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine
      123-labelled tracer molecules. Available tracers for mapping sympathetic neurones
      can be divided into radiolabelled catecholamines, such as 6-[18F]fluorodopamine,
      (-)-6-[18F]fluoronorepinephrine and (-)-[11C]epinephrine, and radiolabelled
      catecholamine analogues, such as [123I]meta-iodobenzylguanidine, [11C]meta
      hydroxyephedrine, [18F]fluorometaraminol, [11C]phenylephrine and meta
      [76Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and
      catechol-O-methyl transferase simplifies the myocardial kinetics of the second
      group. Both groups of compounds are excellent agents for an overall assessment of
      sympathetic innervation. Biomathematical modelling of tracer kinetics is
      complicated by the complexity of the steps governing neuronal uptake, retention
      and release of these agents as well as by their high neuronal affinity, which
      leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic
      neurones is limited by a low density and focal distribution pattern of these
      neurones in myocardium. Available tracers are derivatives of vesamicol, a
      molecule that binds to a receptor associated with the vesicular acetylcholine
      transporter. Compounds like (-)-[18F]fluoroethoxybenzovesamicol display a high
      degree of non-specific binding in myocardium which restricts their utility for
      cardiac neuronal imaging.

PMID- 12002721
TI  - Kidney failure after treatment with 90Y-DOTATOC.

PMID- 12002722
TI  - An original approach in the diagnosis of early breast cancer: use of the same
      radiopharmaceutical for both non-palpable lesions and sentinel node localisation.

PMID- 12002723
TI  - Report from the 41st annual meeting of the Japanese Society of Nuclear Medicine.

PMID- 12002724
TI  - Ultra-high resolution single photon emission tomography imaging of the mouse
      striatum.

PMID- 12002725
TI  - Specific allergen immunotherapy: time for alternatives?

PMID- 12002726
TI  - Evidence of an affinity threshold for IgE-allergen binding in the percutaneous
      skin test reaction.
AB  - BACKGROUND: Atopy is an aberrant immune response involving allergen-specific IgE
      production, though serum IgE concentration is not an entirely reliable diagnostic
      tool, particularly for epidemiological and genetic studies. There is no clear
      correlation between IgE and other indicators of atopy such as skin prick tests
      (SPT)s, and physiological associations are difficult to justify in cases with
      detectable IgE but negative SPT results. OBJECTIVE: IgE reflects the number of
      molecules available to produce an atopic response, but the degree of the response
      is determined by the binding strength (affinity) between receptor-bound IgE and
      the allergen. We sought to determine if there was an association between binding
      affinity and SPT results in people with histories of atopy. METHODS: Standard
      SPTs (whole allergen extracts) were administered to people with histories of
      sensitivities to ragweed and house dust mite. The concentrations and affinities
      of serum allergen-specific IgEs were determined using the purified allergens Amb
      a 1 and Der p 1. RESULTS: There was a positive correlation between weal area and
      allergen-specific IgE among SPT-positive donors. However, for those individuals
      with detectable amounts of allergen-specific IgE, there was considerable overlap
      of IgE values between SPT-positive and -negative groups. Among sensitized donors,
      IgE-allergen interactions were characterized by two or three specific reactions
      of very high affinity (K(A) range 10(8) -10(11) M). Negative SPT reactions were
      associated with lowered IgE binding affinities to major allergens. This delimited
      two groups with atopic disorders: specific IgE(+)/ SPT(+) and specific
      IgE(+)/SPT(-). CONCLUSION: The product of antibody affinity and concentration,
      which we define as antibody capacity (CAP = K(A) x IgE), is more informative with
      regard to describing allergen sensitivity than antibody concentration alone.
      Antibody binding capacity provides physiological evidence of atopy in some
      subjects who do not test positively by common methods and suggests an affinity
      threshold to produce a positive SPT reaction.

PMID- 12002727
TI  - Understanding the usefulness of specific IgE blood tests in allergy.

PMID- 12002728
TI  - The effect of anti-allergic mattress encasings on house dust mite-induced early-
      and late-airway reactions in asthmatic patients. A double-blind, placebo
      controlled study.
AB  - BACKGROUND: Anti-allergic mattress encasing may provide clinical benefit in
      asthmatic patients. However, the effect of mattress encasings on allergen
      specific parameters, such as bronchial reactions to house dust mite (HDM)
      challenge, is not clear. OBJECTIVE: To investigate the effect of anti-allergic
      mattress encasings on allergen sensitivity in patients with moderate to severe
      asthma. METHODS: Twenty-seven patients with asthma and HDM allergy were studied
      in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides
      pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of
      treatment; bronchial histamine challenge, bronchial challenge with HDM and
      intradermal skin challenges with HDM were performed. The number of eosinophils in
      peripheral blood was assessed. RESULTS: In the active group, but not in the
      placebo group, there was a significant reduction in Der p 1 concentration in the
      dust collected from the mattresses after 1 year of treatment compared to before.
      There was a significant difference between the groups with respect to HDM-induced
      early-reaction (ER) in the airways and the number of blood eosinophils, which
      reflected an increase in ER and eosinophils in the placebo group without
      significant change in the active group. No significant improvement in PC20
      histamine, late-reaction (LR) and skin tests was found in either groups.
      CONCLUSION: Our data suggest that encasings protect against a further increase in
      allergen sensitivity in asthmatic patients, so their use should be recommended.

PMID- 12002729
TI  - A comparison of once daily fexofenadine versus the combination of montelukast
      plus loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic
      rhinitis.
AB  - BACKGROUND: The combination of montelukast (ML) and loratadine (LT) has
      previously been shown to be superior to either drug alone in managing seasonal
      allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better
      than LT as monotherapy. OBJECTIVES: We wished to compare ML + LT vs. FEX alone
      for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and
      symptoms. METHODS: Thirty-seven patients with SAR (skin prick positive to grass
      pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled
      cross-over study during the grass pollen season, comparing 2 weeks of once daily
      treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day
      placebo run-in and washout prior to each randomised treatment. The average of
      am/pm PIF (the primary outcome variable) was analysed. Patients recorded their
      symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching
      and sneezing with; total eye symptoms, ocular cromoglycate use, and daily
      activity. The total nasal symptom score was calculated as a composite (out of
      24). RESULTS: There were no significant differences between baselines after the
      run-in and washout placebos for any variables. There were significant (P < 0.05,
      Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with
      both treatments for all end-points, but no differences between the two treatment
      regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98
      107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4 (6.7
      2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7). CONCLUSIONS: Once daily FEX as
      monotherapy was equally effective as the combination of once daily ML + LT in
      improving nasal peak flow and controlling symptoms in SAR. Further studies are
      indicated to assess whether ML confers additional benefits to FEX in SAR.

PMID- 12002730
TI  - An evaluation of the effects of high-dose fexofenadine on the central nervous
      system: a double-blind, placebo-controlled study in healthy volunteers.
AB  - BACKGROUND: As regards central nervous system (CNS) effects there are three types
      of antihistamines. Those that cross the blood-brain barrier and cause widespread
      impairment of cognitive and psychomotor function; those that cross into the brain
      and, although without much impairment at low clinical doses, have a dose-related
      relationship to impairment; and those that do not cross into the brain and
      therefore possess no intrinsic potential for impairing CNS function. OBJECTIVE:
      [corrected] To investigate the acute effects of fexofenadine (360 mg) on various
      aspects of cognitive and psychomotor function in comparison to placebo and
      promethazine (positive internal control), an antihistamine known to produce
      psychomotor and cognitive impairment. METHODS: Fifteen healthy volunteers
      received fexofenadine 360 mg, promethazine 30 mg and placebo in a 3-way cross
      over, double-blind study. For each treatment condition, subjects were required to
      perform a series of tests of cognitive function and psychomotor performance at
      baseline and 1, 3, 5 and 7 h post-dose. The test battery consisted of critical
      flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task
      (CTT) and a subjective assessment of sedation (LARS). RESULTS: Fexofenadine was
      not distinguishable from placebo in any of the objective and subjective tests for
      up to seven hours following drug administration. However, all measures were
      significantly impaired following the administration of promethazine, which
      confirms the sensitivity of the test battery for sedation. The effects of
      fexofenadine and placebo were not significantly different from one another,
      whereas promethazine caused an overall reduction in CFF thresholds when compared
      to placebo (P < 0.05). There was an overall significant increase (impairment) in
      recognition, motor and total reaction time (P < 0.05), and both the tracking
      accuracy and reaction time aspects of CTT were significantly impaired (P < 0.05)
      following the administration of promethazine. In contrast, the effects of
      fexofenadine could not be distinguished from the placebo condition. Subjective
      ratings of sedation were significantly higher with promethazine when compared to
      placebo (P < 0.05) and fexofenadine (P< 0.05). CONCLUSIONS: Fexofenadine at a
      dose of 360mg is demonstrably free from disruptive effects on aspects of
      psychomotor and cognitive function in a study where the psychometric assessments
      have been shown to be sensitive to impairment, as evidenced by the effects of the
      verum control promethazine 30 mg. The identification of an antihistamine
      (fexofenadine) devoid of central effects even at supraclinical doses separates it
      from currently available first and second generation drugs with no objective
      evidence of CNS side-effects on cognition and psychomotor function, and
      highlights the need for the introduction of a third generation of non-sedative
      antihistamines.

PMID- 12002731
TI  - Transient contribution of mast cells to pulmonary eosinophilia but not to hyper
      responsiveness.
AB  - BACKGROUND: We have recently demonstrated that the transfer of interleukin (IL)-5
      producing CD4+ T cell clones into unprimed mice is sufficient for the development
      ofeosinophilic inflammation in the bronchial mucosa upon antigen inhalation.
      OBJECTIVE: The aim of this study was to elucidate the possible contribution of
      mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR),
      and to discriminate between the roles of CD4+ T cells and mast cells. METHODS:
      Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates
      (WBB6F1-+/+) were immunized with ovalbumin and challenged by inhalation with the
      relevant antigen. RESULTS: Airway eosinophilia was induced with equivalent
      intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In
      contrast, 48 h after antigen challenge, eosinophilic infiltration into the
      bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice.
      Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were
      administered next, demonstrating that the airway eosinophilia of W/Wv mice
      induced 48 h after antigen challenge was almost completely inhibited by each of
      these three treatments, but that of +/+ mice was significantly less susceptible.
      Bronchial responsiveness to acetylcholine was increased 48 h after antigen
      challenge and was not significantly different between +/+ and W/Wv mice.
      Administration of anti-IL-5 mAb completely inhibited the development of BHR in
      both +/+ and W/Wv mice. CONCLUSION: These results indicate that, in mice, mast
      cells do have a supplemental role in the development of pulmonary eosinophilia
      but not BHR. CD4+ T cells totally regulate these responses by producing IL-5.

PMID- 12002732
TI  - Is Th1 the solution for Th2 in asthma?

PMID- 12002733
TI  - Mucosal tolerance as therapy of type I allergy: intranasal application of
      recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of
      allergic immune responses and airway inflammation in sensitized mice.
AB  - BACKGROUND: Several studies have demonstrated that mucosal administration of
      soluble antigens can prevent the onset or reduce the severity of certain
      autoimmune diseases or allergies. Few studies exist showing the efficacy of
      mucosal tolerance for therapy of such diseases. OBJECTIVE: The aim of the present
      study was to modulate an allergic immune response by intranasal antigen
      administration in an already sensitized organism. METHODS: A murine model of
      allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized.
      Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in
      different concentrations and at different intervals. On the day the mice were
      killed, blood and bronchoalveolar lavage fluids were taken and immediate type I
      skin tests were performed. T cell proliferation and cytokine production
      (interleukin (IL)-5, interferon (IFN)-gamma) were measured in spleen and lung
      cell cultures. RESULTS: Mucosal treatment with rBet v 1 (3 x 50 microg in 4 day
      intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin
      (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-gamma production
      in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e.
      eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly
      suppressed by the treatment. CONCLUSION: Our results demonstrate that intranasal
      treatment with rBet v 1 reduced systemic allergic immune responses as well as
      airway inflammation in BP-sensitized mice. We therefore suggest that mucosal
      tolerance induction with recombinant allergens could be a promising concept for
      the therapy of allergic diseases.

PMID- 12002734
TI  - Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a
      common aetiology. A population-based study using computerized general practice
      data.
AB  - BACKGROUND: The recent rise in the prevalence of immune-mediated diseases has
      been attributed to environmental factors such as a lack of microbial challenge,
      or dietary change, that deviate the overall balance between mutually antagonistic
      subsets of T helper (Th) cells. OBJECTIVE: An alternative proposal is that recent
      environmental changes have resulted in an immune system that is more likely to
      produce both Th1 and Th2 responses against benign antigens. The prediction of
      this hypothesis, that Th1 and Th2-mediated diseases are not mutually exclusive,
      and may be positively associated, is tested here in a whole population. METHODS:
      Data from General Practices participating in the Scottish Continuous Morbidity
      Recording (CMR) project were used to determine the coincidence of the major Th2
      mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1
      mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and
      psoriasis. We also identified the prescription rates of inhaled therapy for
      asthma in patients with Th1-mediated disease. RESULTS: There was a significant
      increase in the risk of presenting with a Th1-mediated autoimmune condition in
      patients with a history of allergic disease (standardized prevalence ratio (95%
      confidence interval) 1.28 (1.18-1.37)). Likewise, the standardized prevalence
      ratios of presenting with either eczema (1.67 (1.48-1.87)) or allergic rhinitis
      (1.22 (1.02-1.44)) were significantly increased in subjects with a history of Th1
      mediated disease. There was a particularly strong association between current
      psoriasis and current eczema (standardized prevalence ratio ofpsoriasis in
      subjects with eczema 2.88, 95% confidence interval (CI) 2.38-3.45). There was
      also a significant increase in prescriptions for inhaled asthma therapy in
      patients with Th1 disease. CONCLUSION: It is concluded that Th1- and Th2-mediated
      diseases are significantly associated in a large General Practice population.
      This finding supports the proposal that autoimmune and atopic diseases share risk
      factors that increase the propensity of the immune system to generate both Th1-
      and Th2-mediated inappropriate responses to non-pathological antigens.

PMID- 12002735
TI  - Leukotriene receptor antagonists for the treatment of allergic rhinitis.

PMID- 12002736
TI  - Antenatal determinants of neonatal immune responses to allergens.
AB  - BACKGROUND: The environmental factors responsible for recent increases in the
      prevalence of asthma and atopic disease have been assumed to act after birth.
      Their possible effects on fetal immune development in utero have not been
      investigated systematically, although sensitization to allergens may occur before
      birth. OBJECTIVE: This prospective study determined whether the risk factors for
      asthma and atopic disease, namely family history of atopic disease, maternal
      smoking, birth order, or maternal dietary intake of antioxidant vitamins, exert
      antenatal effects on the fetal immune system that may predispose to childhood
      atopy. METHODS: The T helper (Th) cell proliferative responses of cord blood
      mononuclear cells (CBMC) from a sample of 223 neonates, representative of
      children born to a cohort of 2000 pregnant women, were measured and related to
      family, maternal and environmental factors associated with the pregnancy.
      RESULTS: The magnitude of CBMC-proliferative responses to allergens increased
      significantly in association with a family history of atopic disease or maternal
      smoking, and decreased significantly with increasing birth order and high
      maternal dietary intake of vitamin E. The epidemiological association between
      birth order and atopy may therefore be a consequence of antenatal influences
      rather than of protective effects of childhood infections. The association
      between maternal intake of vitamin E and CBMC responsiveness suggests that diet
      during pregnancy may influence the fetal immune system in such a way as to
      modulate the risk of childhood atopy. CONCLUSION: These results provide a new
      insight into the aetiology of atopic disease by demonstrating that the maternal
      environmental risk factors for atopy, diet, birth order and smoking, influence
      the development of the fetal immune system. This raises the prospect of
      preventative public health interventions during pregnancy.

PMID- 12002737
TI  - The association between persistent eosinophilia and asthma in childhood is
      independent of atopic status.
AB  - BACKGROUND: Although peripheral blood eosinophilia is associated with risk of
      asthma, the relation with atopy has not been established. OBJECTIVE: To assess
      the relationship between eosinophils and chronic asthma in childhood, and to
      determine the factors associated with eosinophil levels over time. METHODS:
      Percent eosinophils/300 white blood cell (WBC) count ('eos') was measured at 9
      months, 6 years and 11 years in subjects participating in the prospective Tucson
      Children's Respiratory Study. Children were classified based on the number of
      measurements in which they had low (< or = 2%) or high (>5%) eosinophils, as
      follows: (1) Persistently low eos (n = 130); (2) Low eos (intermittently low or
      consistently moderate, but never high, n = 317); (3) Intermittently high eos (n =
      192); and (4) Persistently high eos (n = 17). Only children with > or = 2 eos
      measurements were included in the analysis. Chronic asthma was defined as medical
      doctor (MD)-diagnosed asthma with reports of wheezing during the previous year,
      on > or = 3 questionnaires completed between 2 and 13 years of age. Children with
      at least one positive skin prick test (SPT; > or = 3 mm) at age 6 or 11 were
      considered 'atopic'. RESULTS: Chronic asthma was linearly related to
      longitudinally ascertained eosinophils (trend chi2 P<0.001) with prevalence
      ranging from 5.8% among children with persistently low eos to 37.5% among
      children with persistently high eos. This relation was independent of atopy.
      Parental history of asthma was associated with both chronic asthma (P <0.001) and
      with longitudinal eosinophil status (P < 0.001). After adjusting for atopy and
      gender, there was a 70% increase in asthma risk with each increase in
      longitudinal eosinophil level. This stepwise increase was reduced to 48% when
      parental asthma was added to the model. CONCLUSION: Longitudinal eosinophil
      levels are linearly associated with chronic asthma in childhood, independent of
      atopy. The strong association between parental asthma and eosinophil status
      suggests that genetic background may be an important determinant of eosinophilic
      response.

PMID- 12002738
TI  - The relationship between airway hyper-responsiveness, markers of inflammation and
      lung function depends on the duration of the asthmatic disease.
AB  - BACKGROUND: The combination of airway hyper-responsiveness, eosinophilic airway
      inflammation, and lung function impairment is considered as a hallmark of
      bronchial asthma. Since airway function might change with time in chronic asthma,
      the association between parameters which are characteristic of asthma could be
      different in subjects with different durations of the disease. OBJECTIVE: We
      assessed whether in patients with asthma the relationship between airway
      hyperresponsiveness, non-invasive markers of airway inflammation, and baseline
      lung function depended on the duration of the disease. METHODS: Sixty-six non
      smoking patients with mild to moderate allergic asthma without corticosteroids
      were assigned to two groups, according to a duration of the disease (time
      interval since doctor's diagnosis) of either < or = 16 years (median 8 years;
      mean FEV1, 92.6% pred.; n = 34) or > 16 year (median 25 years; mean FEV1, 87.9%
      pred.; n = 32). RESULTS: Groups did not differ statistically in PC20FEV1 of
      methacholine, sputum composition, levels of exhaled nitric oxide (NO), lung
      function parameters, or history of treatment. There were significant correlations
      between PC20FEV1, eosinophils and NO in patients with a duration of the disease <
      or = 16 year, but no relation to lung function. In contrast, patients with a
      duration > 16 year showed a correlation between PC20FEV1 of methacholine and lung
      function but not eosinophils or NO. In both groups, eosinophils and NO were
      associated with each other. These results were corroborated by the statistical
      procedure of factor analysis that revealed 'inflammation' and 'lung function' as
      major entities and found 'responsiveness' to be associated with only one of them
      in each group. CONCLUSION: Our data demonstrate that with a shorter duration of
      the asthmatic disease airway hyper-responsiveness is associated with airway
      inflammation, whereas with a longer duration it is associated with impaired lung
      function, suggesting that in chronic asthma ongoing alterations become the
      primary determinant of functional characteristics.

PMID- 12002739
TI  - Increased nasal mucosal swelling in subjects with asthma.
AB  - OBJECTIVE: The objective of this study was to evaluate nasal mucosal swelling
      with acoustic rhinometry in subjects with asthma and in healthy controls.
      METHODS: We examined 184 individuals with asthma and compared with 156 randomly
      selected controls outside the pollen season, where 144 subjects in the asthma
      group and 80 controls had a previous history of non-infectious rhinitis (NIR).
      Nasal mucosal swelling was assessed with acoustic rhinometry before and after
      nasal decongestion with oxymetazoline and was analysed for the crosssectional
      area (4cm from the nostril) and the volume between 3.3 and 4cm from the nostril.
      Symptom scores for nasal blockage, secretion, itching and sneezing were assessed
      on a 0-10 visual analogue scale as well as peak nasal inspiratory flow and
      spirometry. RESULTS: Before decongestion there was a decrease in the cross
      sectional area at 4 cm (1.32 cm2 vs. 1.59 cm2, mean left + right P = 0.04) and in
      the volume (1.70 vs. 1.91 cm3 P = 0.03) in the asthma group compared with healthy
      controls. After decongestion there were no significant differences in cross
      sectional area at 4cm (1.66 vs. 1.73cm2 P=0.32) or volume (2.12 vs. 2.24cm3
      P=0.32). Combined nasal symptom scores were higher in the asthma group (1.8 vs.
      0.8, P=0.0001) and peak nasal inspiratory flow was lower (119 vs. 124 L/min, P =
      0.38) than the healthy controls. FEV1 (% predicted) was also lower in asthma
      group (84 vs. 93% P < 0.0001). CONCLUSION: We have been able to demonstrate an
      increased nasal mucosal swelling in a population sample of persons with asthma
      compared to healthy controls. These data support previous reports of a
      generalized airway inflammation in patients with asthma and suggest that acoustic
      rhinometry can be used to monitor the nasal mucosal swelling in these patients.

PMID- 12002740
TI  - Natural course of sensitization to cow's milk and hen's egg in childhood atopic
      dermatitis: ETAC study group.
AB  - BACKGROUND: Sensitization to food allergens has been implicated in the
      pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of
      the present paper is to investigate the natural course of sensitization to egg
      and to cow's milk and its relationship with the severity of AD. METHODS: The
      placebo intention-to-treat population of the ETACTM (Early Treatment of the
      Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean+
      SD: 17.2 + 4.1 months) who were followed for 18 months. All children were
      examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE
      amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18
      months. Fifteen patients were excluded from this analysis due to major protocol
      violations thus leaving 382 patients in the analysed population. RESULTS:
      Sensitization to egg and to cow's milk was more common in atopic children with
      severe AD at all time-points. At inclusion, children sensitized to both egg and
      to cow's milk had the most severe AD (Kruskall-Wallis test P= 0.007). The degree
      of sensitization expressed in RAST classes was significantly related to the
      severity of AD. Furthermore, children sensitized to egg or to cow's milk at
      inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs.
      57% in those not sensitized) and a higher objective SCORAD after 18 months follow
      up. CONCLUSION: We found an association between severity of AD and sensitization
      to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent
      cow's milk, indicates a worse outcome of AD in terms of persistence and severity
      of the disease.

PMID- 12002741
TI  - Determination of allergenicity to three cow's milk hydrolysates and an amino acid
      derived formula in children with cow's milk allergy.
AB  - BACKGROUND: Products based on hydrolysed cow milk proteins or amino acid mixtures
      are recommended in children with cow's milk hypersensitivity. However, some
      children who are allergic to cow's milk and who clinically react to substitute
      milk formulas have been observed. OBJECTIVE: To determine the tolerance and
      allergenicity of protein hydrolysate or amino acid-derived formulas in children
      with IgE-mediated cow's milk allergy. METHODS: Twenty children with positive
      cow's milk challenges, positive skin prick tests and/or serum-specific IgE
      antibodies to cow's milk were selected. Oral challenges, skin prick tests and
      serum-specific IgE antibodies to extensively hydrolysed whey formula, partially
      hydrolysed whey formula, extensively hydrolysed casein formula and amino acid
      derived formula were performed. RESULTS: Five out of 17 (5/17) children reacted
      to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey
      formula, (2/10) to amino acid-derived formula, (1/16) to extensively hydrolysed
      casein formula. Only extensively hydrolysed casein formula was tolerated by at
      least 90% (with 95% confidence intervals) of children. Hydrolysates provoked
      early and delayed clinical reactions, amino acid mixtures only delayed reactions.
      Partially hydrolysed whey formula elicited a significantly higher number of
      positive skin prick test reactions than other formulas. Two children had specific
      IgE antibodies to extensively hydrolysed whey formula, one to partially
      hydrolysed whey formula, one to extensively hydrolysed casein formula and none to
      amino acid-derived formula. CONCLUSION: In this study, none of the cow's milk
      substitutes has been found to be non-allergenic. Our results suggest that in
      children with IgE-mediated cow's milk allergy, the first ingestions of
      extensively hydrolysed cow's milk protein formulas require strict medical
      supervision because of immediate reactions. This is not the case for amino acid
      derived formula. Moreover, our data suggest that treatment of children allergic
      to cow's milk with cow's milk substitutes should be monitored for several days to
      document tolerance.

PMID- 12002742
TI  - The return of the basophil.

PMID- 12002743
TI  - An ELISA for recombinant Lepidoglyphus destructor, Lep d 2, and the monitoring of
      exposure to dust mite allergens in farming households.
AB  - BACKGROUND: Exposure to indoor allergens, such as dust mites, has been recognized
      as a risk factor for sensitization and symptoms. OBJECTIVE: To develop a two-site
      ELISA for the determination of Lep d 2 in the reservoir, to measure dust mite
      allergen exposure (Lep d 2, Der p 1, Der f 1 and Der 2) in farm households, and
      to investigate whether exposure to these allergens is associated with
      sensitization, asthma and rhinoconjunctivitis. METHODS: Monoclonal antibodies to
      recombinant (r)Lep d 2 were produced with standard hybridoma technique. Dust
      samples from 393 households were analysed for allergen content by two-site ELISA
      methods. RESULTS: A two-site Lep d 2 ELISA was developed with a detection limit
      of 0.09 microg/g. The assay was highly reproducible and levels of Lep d 2 showed
      a strong correlation with the number of Lepidoglyphus mites (r(s): 0.7; P =
      0.0002). Lep d 2 was detected in 20% of the homes; levels ranged from 0.09 to 1.7
      microg/g of dust. Der p 1 was recorded in 59% of the samples, ranging from 0.055
      to 139 microg/g, and Der f 1 and Der 2 in 40% and 50% of the samples, ranging
      from 0.055 to 24.5 microg/g and 24.3 microg/g, respectively. Dermatophagoides
      allergens were significantly higher in mattresses than in carpets (P < 0.0001),
      but this difference was not observed with Lep d 2. A strong relationship between
      immunoglobulin (Ig)E to rLep d 2 and asthma (OR = 10.4) and rhinoconjunctivitis
      (OR = 7.5) was seen. Furthermore, sensitization to D. pteronyssinus was
      significantly associated with asthma (OR: 13.7) and rhinoconjunctivitis (OR:
      5.7). CONCLUSION: When assessing mite allergen exposure in rural homes, not only
      the Der p 1, Der f 1 and Der 2 allergens, but also the Lep d 2 allergen should be
      taken into consideration.

PMID- 12002744
TI  - cDNA cloning and heterologous expression of the major allergens from peach and
      apple belonging to the lipid-transfer protein family.
AB  - BACKGROUND: Lipid-transfer proteins (LTPs) have been identified as major
      allergens of Rosaceae fruits in populations living in areas virtually free of
      Fagales trees, such as several Mediterranean communities. Pru p 3 and Mal d 3,
      the allergens from peach and apple, respectively, have a main clinical relevance
      in these areas. OBJECTIVE: To isolate and characterize cDNAs for Pru p 3 and Mal
      d 3, and to produce recombinant Pru p 3 in the yeast Pichiapastoris. METHODS:
      cDNAs for both allergens were isolated by polymerase chain reaction using
      nondegenerated primers. Expression of Pru p 3 was performed in P. pastoris using
      the pPIC 9 vector. The recombinant product was purified by gel-filtration
      chromatography followed by RP-HPLC. Immunodetection and immunoblot inhibition
      assays were carried out with sera from peach-allergic patients. RESULTS: The
      cDNAs for both Pru p 3 and Mal d 3 showed a 273 open reading frame coding for the
      91 amino acid mature polypeptides. The deduced amino acid sequences exhibited N
      terminal regions fully identical to those previously determined for the natural
      peach and apple allergens. Pru p 3 was expressed in P. pastoris at 20 mg/L of
      culture medium. The recombinant allergen showed the same N-terminal sequence
      (plus a glutamic acid added for proper extracellular expression) and apparent
      molecular size as natural Pru p 3. Both the recombinant and natural forms of Pru
      p 3 displayed similar immunoglobulin (Ig)E-binding capacity in immunodetection
      and immunoblot inhibition assays. CONCLUSIONS: Comparison of the complete primary
      structures of mature Pru p 3 and Mal d 3 deduced from their corresponding cDNA
      clones supports the close relationship between both allergens. Recombinant Pru p
      3 binds IgE in vitro like its natural counterpart. Therefore, it can be a useful
      tool for specific diagnosis and structural studies.

PMID- 12002745
TI  - New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid
      DP receptor genes.
AB  - BACKGROUND: Prostaglandin D2 (PGD2), a major cyclo-oxygenase metabolite of
      arachidonic acid in mast cells, induces bronchoconstriction in the human lung. It
      has been reported that mice lacking PGD receptor fail to develop the bronchial
      hyper-responsiveness upon ovalbumin challenge, suggesting that PGD2 functions as
      a mediator of allergic asthma. OBJECTIVE: To determine if there are any mutations
      associated with the development of asthma in the haematopoietic prostaglandin D
      synthase (H-PGDS) gene and the human prostanoid DP receptor (PTGDR) gene. METHODS
      AND RESULTS: We screened the 5'flanking and coding regions of the H-PGDS gene and
      the PTGDR gene by direct sequence. We identified one variant in intron 2 (IVS2 +
      11 A > C) and one variant in intron 3 (IVS3 + 13T > C) of the H-PGDS gene, and
      two variants in the 5'flanking region of the PTGDR gene (-197T > C and -2C > T).
      The IVS3 + 13T > C and -197T > C variants were rare, appearing only once in 48
      subjects. transmission disequilibrium test (TDT) analysis of 144 asthmatic
      families revealed that the IVS2 + 11 A allele of the H-PGDS gene was
      significantly transmitted preferentially to asthma-affected children (P =
      0.0056), but no association was observed between -2C/T polymorphism of the PTGDR
      gene and asthma (P > 0.05). CONCLUSION: Our results suggest that the IVS2 + 11A/C
      allele may be involved in the development of asthma in the Japanese population.

PMID- 12002746
TI  - Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood
      mononuclear cells from atopics vs. non-atopics.
AB  - BACKGROUND: T helper (Th)2 cytokines are considered to play a central role in the
      induction and expression of allergic disease. However, the relative importance of
      individual cytokines is unclear, and overall disease pathogenesis appears to
      involve the coordinate activities of a range of Th2 cytokines acting in sequence
      or in parallel. The present study examines an alternative approach to the study
      of cytokine gene function in atopy, focusing instead upon T cell transcription
      factors (TFs) which play a role in the regulation of multiple cytokine genes.
      OBJECTIVE: To investigate the allergen-induced expression of the TF GATA-3 and c
      Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th
      polarization. METHODS: PBMC from house dust mite (HDM)-atopic and non-atopics
      were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was
      analysed by semiquantitative RT-PCR and major findings were validated by real
      time PCR. Cell separations were performed to analyse the contribution of CD45RO+
      cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous
      cytokines and TF expression analysed by Northern blot and real-time PCR. Results
      We demonstrate for the first time that during differentiation of CD4+ CD45RA+
      naive human T cells towards Th2 commitment, and during allergen-specific
      reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics,
      expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T
      cells from non-atopics display equally rapid GATA-3 down-regulation under
      identical conditions of allergen stimulation. CONCLUSION: These findings identify
      Th2-associated TFs as key determinants of the atopic phenotype, suggesting their
      unique potential as therapeutic targets for disease control.

PMID- 12002747
TI  - Chemokine receptors and stromal cells in the homing and homeostasis of chronic
      lymphocytic leukemia B cells.
AB  - Chronic lymphocytic leukemia (CLL) is a disease characterized by an accumulation,
      of mature, functionally incompetent B lymphocytes in the blood, secondary
      lymphoid tissues, and marrow. Lymphocyte trafficking and homing to specialized
      microenvironments is an active process that depends on the sequential engagement
      of adhesion molecules and activation through chemokine receptors. CLL B cells
      express functional CXCR3, CXCR4, and CXCR5 chemokine receptors that can direct
      leukemia cell chemotaxis in vitro. Marrow stromal cells, blood-derived "nurse
      like cells", and extramedullary stromal cells of mesenchymal origin secrete high
      amounts of stromal cell-derived factor-1 (SDF-1) and thereby can attract CLL B
      cells via CXCR4. In vitro, CLL cells are rescued from apoptosis by cell-cell
      contact with such cells. Moreover, we found that the capacity of these cells to
      protect leukemia cells from apoptosis in vitro is mediated, at least in part, by
      the SDF-1 chemokine. Taken together, these findings suggest that chemokines and
      their receptors on CLL B cells can govern the homing and survival of leukemia B
      cells in vivo and therefore may contribute to their noted resistance to
      chemotherapy-induced apoptosis. Conceivably, CXCR4, and possibly other chemokine
      receptors, may represent a novel target for the development of effective
      treatment of this disease.

PMID- 12002748
TI  - Hemochromatosis gene in leukemia and lymphoma.
AB  - The gene causing hereditary hemochromatosis (HH), HFE is an HLA class I-like gene
      with no known immunological function but indirectly related to the immune
      functions because of its role in iron transport. It is located 6.5 Mb telomeric
      to HLA-A. The most common mutation of HFE, C282Y, has a Celtic origin and most
      patients with HH are homozygous for it in Northern European populations. While
      there is an enormously increased risk for hepatocellular cancer in
      hemochromatosis that is attributed to the toxic effects of iron, the risk for
      extra-hepatic cancers is also increased slightly. Recent studies have found
      genetic associations between several cancers and C282Y but only in the presence
      of a particular allele of the transferrin receptor gene. This suggests that the
      increased cancer risk is more likely due to the effects of iron. In childhood
      acute lymphoblastic leukemia (ALL), however, there is a strong association of
      C282Y with a gender effect in two different Celtic populations. This association
      does not require homozygosity for C282Y or an interaction with the transferrin
      receptor gene, and is male-specific. The other HFE mutation H63D does not confer
      increased risk to childhood ALL. Acute myeloblastic leukemia and Hodgkin's
      disease in adults do not have an association with HFE. Its male-specificity,
      occurrence in childhood and the lack of a gene-dosage effect suggest that the
      C282Y association in childhood ALL may reflect the involvement of another HLA
      linked gene in leukemia susceptibility.

PMID- 12002749
TI  - Kell expression on myeloid progenitor cells.
AB  - Kell is one of the major human red blood cell groups and comprises 22 antigens.
      These antigens are produced by alleles located on chromosome 7, including sets of
      antithetical antigens such as Kell (K, K1) and cellano (k, K2), which differ in a
      single amino acid change (T193M). It consists of a 93-Kd transmembrane
      glycoprotein that is surface-exposed and shares sequence and structural homology
      with zinc endopeptidases, which are involved in regulating bioactive peptides.
      Anti-Kell antibodies have been shown to suppress fetal erythropoiesis. Recently
      published data indicate a similar effect on myeolopoiesis and megakaryopoiesis.
      Substantial thrombocytopenia in fetuses affected with HDN due to anti-K
      antibodies led to the discovery of the inhibitory effect of Kell-related
      antibodies on CFU-MK growth. In addition to its inhibitory effect on BFU-E
      growth, anti-Kell antibodies significantly reduced CFU-GM colony formation from
      haematologically normal individuals. Moreover, anti-cellano and anti-Kp(b)
      antibodies also inhibited the growth of CFU-GM from antigen positive MNC. These
      data indicate that Kell is not restricted to erythroid blood cells, but is
      expressed on a broader spectrum of haematopoietic cells than previously believed.

PMID- 12002750
TI  - The insulin-like growth factor system in hematopoietic cells.
AB  - The insulin-like growth factor (IGF) system regulates proliferation and
      differentiation of hematopoietic cells. IGFs exert their effects through specific
      receptors on growing and differentiating blood cells as they emerge from their
      small pool of ancestral stem cells. The IGF system is complex as both stimulating
      and inhibiting effects occur by interaction of IGFs and IGF-binding proteins
      (IGFBPs). IGFs stimulate erythrocytes and lymphocytes but also promote leukemic
      hematopoietic cell proliferation. IGF-I appears to be correlated with hemoglobin
      levels in anemia and could also be of benefit for patients with bone marrow
      aplasia after transplantation. Hypersensitivity to IGF-I has been implicated as
      an underlying cause of polycythemia vera. Loss of imprinting of IGF-II is found
      in acute myeloid leukemia and myelodysplastic syndrome. Apoptosis of
      hematopoietic cells is significantly reduced by IGF-I involving an intriguing
      signal transduction pathway. IGFs could therefore, although not classical
      hematopoietic growth factors, be of benefit for patients with diverse
      hematopoietic disorders.

PMID- 12002751
TI  - Cell cycle regulation in human hematopoietic stem cells: from isolation to
      activation.
AB  - Hematopoietic stem cells (HSCs) reside mostly in the bone marrow and are defined
      by their ability to self-renew and to give rise by proliferation and
      differentiation to all blood lineages. Despite this strict definition HSCs cannot
      be unequivocally identified in the hematopoietic cell pool. Despite innumerable
      studies over the years, which focused on the search of the ideal phenotypic
      marker to selectively isolate stem cells, most of the known markers still define
      heterogeneous populations in different stages of commitment. Functional features
      attributed to stem cells have also been investigated, and among these the use of
      fluorescent markers which allow tracking of the cell division record of each
      cell. A second issue, after the initial isolation process, is the expansion ex
      vivo in order to obtain production of large numbers of homogeneous cell
      populations for both biological studies and clinical applications. Expansion ex
      vivo is difficult to modulate and normally occurs only along with commitment and
      consequent loss of multipotentiality. Moreover expansion obtained ex vivo is
      significantly reduced to that achievable in vivo. One of the key features of HSCs
      is a very slow proliferation rate, but when the appropriate stimuli are
      delivered, the proliferation rate can drastically increase. In normal
      physiological conditions a strict balance is maintained between the number of
      cells that maintain the original pool and those that proliferate and
      differentiate. Numerous data in recent years are providing some clue to elucidate
      the key steps in this tightly controlled process, but the dynamics that regulate
      which and how many cells self-renew to maintain the pool, and which proliferate
      and become committed to give rise to the mature blood elements, are still
      unclear.

PMID- 12002752
TI  - Influence of tumor vaccines on graft versus tumor activity and graft versus host
      disease in allogeneic bone marrow transplantation.
AB  - Powerful immunologically-mediated antitumor efforts can be observed in allogeneic
      hematopoietic stem cell transplantation. In the absence of specific immune
      interventions, this graft versus tumor effect is closely associated with graft
      versus host disease. In the work summarized here, the influence of cellular tumor
      vaccines on graft versus tumor activity and graft versus host disease is examined
      in a murine model of MHC-matched, minor histocompatibility antigen-mismatched
      bone marrow transplantation. The experiments have generated the following
      conclusions. First, complex cellular vaccines, which include recipient minor
      histocompatibility antigens, when administered to allogeneic donors generate
      powerful graft versus tumor effects but also induce unacceptable exacerbations of
      graft versus host disease. Second, cellular tumor vaccines, which contain
      recipient minor histocompatibility antigens, can be administered to transplant
      recipients after transplant without significant exacerbation of GVHD and with
      retention of clinically significant graft versus tumor effects. Third,
      immunization of donors with molecularly defined tumor-associated antigens, which
      are not recipient minor histocompatibility antigens, can be coupled with post
      transplant immunization of recipients with cellular vaccines without exacerbation
      of GVHD.

PMID- 12002753
TI  - Bone turnover following autologous transplantation in multiple myeloma.
AB  - Most patients with multiple myeloma have lytic lesions at multiple sites in the
      axial skeleton. These lesions commonly give pain and are at risk of pathological
      fracture, and bony disease is therefore a cause of much morbidity in myeloma.
      Recent data indicates that the Receptor Activator of NF-kappaB ligand (RANKL) and
      Osteoprotegerin (OPG) may be central to the local pathogenesis of these lytic
      lesions. Bisphosphonates may ameliorate some of these abnormalities, and
      clinically these agents improve the skeletal prognosis in myeloma patients. High
      dose chemotherapy with autologous stem cell rescue is currently under evaluation
      in the management of myeloma, though little is known of the effect of this
      therapeutic modality on the skeleton. Studies using biochemical markers of bone
      turnover suggest that increased osteoclast activity may be present even in
      apparent plateau phase of myeloma. High dose chemotherapy with autografting may
      normalise abnormal bone resorption, though the effect may take several weeks to
      emerge, and may be paralleled by increased osteoblast activity. The findings
      provide biochemical evidence that autografting may help normalise the abnormal
      bone turnover characteristic of myeloma.

PMID- 12002754
TI  - HHV-8 infection in the transplantation setting: a concern only for solid organ
      transplant patients?
AB  - Early epidemiologic studies have shown an increased risk of Kaposi sarcoma (KS)
      in recipients of solid organ transplants, while KS is exceptional in the setting
      of autologous and allogeneic bone marrow (BM) and peripheral blood stem cell
      (PBSC) transplant patients. The recent discovery of human herpesvirus 8 (HHV-8)
      as the necessary etiologic agent of KS has stimulated studies to assess whether
      KS is the result of HHV-8 transmission from the donor or of reactivation of a pre
      existing HHV-8 infection in the recipient host. An association of HHV-8 infection
      with lymphoid neoplasias has also been observed, identifying this herpesvirus as
      a possible causal agent of some Epstein-Barr virus negative post-transplant
      lymphoproliferative diseases. The recent description of non-neoplastic
      complications associated with HHV-8 reactivation after autologous PBSC
      transplantation, has raised concerns about the spectrum of diseases potentially
      associated with this herpesvirus, even in the setting of BM and or PBSC
      transplantation. The issue of HHV-8 transmission with the grafts, the problems
      inherent with the diagnosis and monitoring of active viral infection, the need
      for prevention and treatment of the clinical consequences of HHV-8 primary
      infection and reactivation cannot be underestimated, at least in areas endemic
      for HHV-8 infection.

PMID- 12002755
TI  - The evaluation of the biological behavior and grade among cases with mantle cell
      lymphoma.
AB  - We have studied the expression of MIB-1 and prognosis in cyclin D1(CyD1)+ and
      CyD1- mantle cell lymphoma (MCL), and compared them to B-CLL/SLL. All cases were
      assigned to four groups by immunoreactivity and primary sites: (1) CyD1+ nodal
      MCL, 11 cases: (2) CyD1+ extranodal MCL (multiple lymphomatous polyposis, (MLP))
      three cases: (3) CyD1- nodal MCL, three cases: and (4) CyD1- B-CLL/SLL, seven
      cases. The average of MIB-1 labeling indexes of the four groups were 30.66, 8.70,
      9.30 and 4.66, respectively. The CyD1- group consisting of nodal MCL and CLL/SLL
      had a significantly longer median survival time (69 months) than the CyD1+ group
      consisting of nodal MCL and MLP (22 months, P = 0.01). These data indicate that
      CyD1- nodal MCL may show a lower MIB-1 labeling index, and has a better
      prognosis, than CyD1+ nodal MCL. In addition, a large difference in the average
      of MIB-1 labeling indexes between nodal MCL and MLP in the CyD1+ group was found.

PMID- 12002756
TI  - Survival and freedom from progression in autotransplant lymphoma patients is
      independent of stem cell source: further follow-up from the original randomised
      study to assess engraftment.
AB  - Peripheral blood progenitor cells (PBPCs) have become the stem cell source of
      choice in autologous transplantation. In a prospective randomised trial, we
      previously demonstrated that autologous transplantation using filgrastim
      mobilised PBPCs resulted in faster haematopoietic recovery with shorter
      hospitalisation and reduced platelet transfusions compared to bone marrow
      transplant (BMT). This study is a follow-up analysis evaluating the long-term
      clinical outcome. Seventy-two patients with advanced Hodgkin's disease or high
      grade lymphoma were randomised to receive either filgrastim-mobilised PBPCs (n =
      37) or bone marrow (n = 35) after BEAM chemotherapy. Fourteen patients withdrew
      from the study before commencing high-dose chemotherapy. Fourteen of the 58
      patients who received treatment with chemotherapy and transplant have died, 6
      (19%) in the ABMT arm and 8 (30%) in the PBPC transplant (PBPCT) arm. Twenty-five
      patients (81%) in the ABMT arm and 17 (63%) in the PBPCT arm, who received
      treatment, were in complete remission at the date of last follow-up. Progression
      free survival and overall survival (OS) were similar for both arms (OS 81% at 46
      months for ABMT versus 63% for PBPC; p = 0.38). Further prospective studies with
      larger number of patients need to be done to assess which source of stem cells
      may translate into a long-term clinical benefit for the patient.

PMID- 12002757
TI  - The role of nucleoside analogues in the treatment of chronic lymphocytic leukemia
      lessons learned from prospective randomized trials.
AB  - The newer purine nucleoside analogues (PNA), fludarabine (FAMP) and cladribine (2
      chlorodeoxyadenosine, 2-CdA) have been synthesized recently and introduced into
      the treatment of chronic lymphocytic leukemia (CLL). The results of large phase
      II studies indicate that FAMP and 2-CdA are similarly active in CLL.
      Unfortunately, no prospective randomized study comparing the results of the
      treatment of CLL patients with FAMP and 2-CdA has been published so far.
      Significantly higher overall response (OR) and complete remission (CR) in
      patients treated initially with PNA than with chlorambucil or cyclophosphamide
      based combination regimens has been recently confirmed in five prospective
      multicentre randomized trials. These studies have also shown longer response
      duration in patients treated with PNA than with conventional chemotherapy.
      Overall survival progression free and events free survival were similar in
      patients treated with PNA and with chlorambucil or other alkylating agent based
      regimens. However, the majority of randomized trials were designed as cross over
      studies and most patients, treated with conventional chemotherapy were given PNA
      when refractory or in early relapse, which may influence the survival time. The
      results of a randomized study have shown a higher incidence of neutropenia and
      infections in patients treated with PNA than with chlorambucil. However. the
      frequency of autoimmune hemolytic anemia, pure red cell aplasia, secondary
      neoplasms and Richter's syndrome seems to be similar in patients treated with PNA
      and standard alkylating agents based chemotherapy. In conclusion, alkylating
      agents still have an important place in the routine management of the majority of
      CLL patients. They are in general safe, given on an out patients basis and
      significantly cheaper than PNA. PNA should be routinely used as second line
      treatment, and possibly as first line therapy in younger patients, who are
      candidates for potentially curative treatment such as stem cell transplantation
      and/or monoclonal antibodies.

PMID- 12002758
TI  - The role of soluble CD23 in distinguishing stable and progressive forms of B
      chronic lymphocytic leukemia.
AB  - Soluble CD23 (sCD23) has been recognized as an important prognostic parameter in
      patients with chronic lymphocytic leukemia (B-CLL) at early clinical stages.
      There is, however, no clear information on its prognostic significance in
      advanced stages and on its role as an indicator for aggressive or indolent
      courses of disease. Therefore, sCD23 was measured in the serum of 145 patients at
      diagnosis and serial determinations were carried out for 8 years in 38 patients.
      The results indicate that in patients with identical clinical stages at first
      presentation the disease could take different courses depending on initial sCD23
      concentrations below or above specific threshold levels (860 and 5900U/ml). sCD23
      higher than these thresholds was associated with faster progression into upper
      clinical stages. Furthermore, sCD23-doubling time (sCD23-DT) indicated that
      patients with long DT progressed slowly, while those with short DT had more
      aggressive disease. Particularly in patients with advanced disease stages, long
      sCD23-DT indicated development of smoldering disease. Since sCD23 levels reflect
      total tumor mass, determination of sCD23-DT has probably a better predictive
      value than lymphocyte doubling time. It appears that B-CLL patients can be
      divided into different risk categories according to initial determinations of
      sCD23 and that sCD23-DT is an additional important parameter in predicting
      disease progression.

PMID- 12002759
TI  - Cleaved lymphocytes in chronic lymphocytic leukemia: a detailed retrospective
      analysis of diagnostic features.
AB  - Through a global analysis of diagnostic features, the aim was to profile CLL
      patients with circulating cleaved lymphocytes at diagnosis, a controversial
      prognostic factor. Although some of them could have been considered today as
      having Non-Hodgkin's lymphoma, all 106 patients of our retrospective series have
      had CLL treatments. Slide review distinguished seven lymphocyte morphotypes. With
      minimal a priori assumptions, excluding in particular clinical staging systems,
      forty-five diagnostic features were analyzed in 37 patients. CORICO (Correlations
      Iconography), a purely geometric method, deciphered the multidimensional
      structure of the raw data. Probabilistic monoparametric tests were made on the
      106 patients. In ten patients (Binet stages: 3A, 6B, 1C), at least 8% of the
      lymphocytes were cleaved. Unrelated to the prolymphocytes, this morphotype had
      neither links with the CD5+CD23+ (9/10 vs 80/86), FMC7+ (5/10 vs 22/62), CD38
      (1/7 vs 7/64) markers nor with any major CLL laboratory values; only three links
      characterized it: no cases of mixed marrow infiltrate (nodular: 1, interstitial:
      6, diffuse: 3; ns), a lower percentage of eosinophils (ns), and predominance of
      CD11c (7/10 vs 20/66, p < 0.02). In conclusion, in contrast to the PLL
      morphotype, or to the lactic dehydrogenase (LDH) activity, which was a strong
      prognostic factor in this series, an independent detrimental value of the cleaved
      morphotype has not yet been found. Our study shows that free of modeling
      constraints, this method makes possible a rapid and objective insight into
      variable interrelations. If further explored in a prospective study, this
      approach may contribute to the understanding of discrepancies in the literature.

PMID- 12002760
TI  - Isolated myelosarcoma in children--update and review.
AB  - Primary myelosarcomas, also called leukemia cutis, granulocytic sarcomas or
      chloromas, are rare extramedullary manifestations of acute myeloid leukemia (AML)
      which precede bone marrow involvement. Skin infiltration was the most frequent
      localization associated with a myelomonocytic differentiation. Although first
      remission was achieved by most children, risk of relapse seemed to be increased.
      This might be caused by the specific biology of myelosarcomas, but also may be
      the result of delayed or reduced treatment. During the AML-BFM-studies 87/93/98
      (11/1987-7/2000) 37 children with isolated myelosarcomas were diagnosed. Eighteen
      of the 37 patients survived with a 5-year overall survival estimation of 0.54+/
      0.09 compared to 0.59+/-0.02; p(log rank) = 0.94. However, reduced or delayed
      treatment in 17 children led to an increased relapse rate of 71% compared to 35%
      in children treated soon after diagnosis. The 5-year overall survival in these
      patients was 0.41+/-0.11. According to our experience and review of the
      literature, an early diagnostic workup is needed in children with unusual skin
      lesions or tumors, considering myelosarcoma as primary manifestation of AML.
      Intensive AML-specific chemotherapy is generally recommended soon after
      diagnosis.

PMID- 12002761
TI  - Stem cell factor-induced bone marrow mast cell hyperplasia mimicking systemic
      mastocytosis (SM): histopathologic and morphologic evaluation with special
      reference to recently established SM-criteria.
AB  - Although systemic mastocytosis (SM) is a well-defined hematologic neoplasm, it is
      sometimes difficult to discriminate between SM and a reactive mast cell (MC)
      hyperplasia. We describe a patient with aplastic anemia who was treated with
      recombinant stem cell factor (SCF). In response to SCF, the patient showed
      transient hematologic improvement and developed a marked increase in MC as well
      as a transient increase in serum tryptase. Histologic and immunohistochemical
      examination revealed a huge increase in MC in the bone marrow with focal
      infiltrates similar to SM. However, most of the SM-criteria were not met: First,
      MC showed normal cytomorphological characteristics without significant atypias
      (no cytoplasmic extensions, no oval nuclei, no hypogranulated cytoplasm).
      Furthermore, bone marrow MC were CD2- and CD25-negative and did not exhibit the C
      KIT 2468 A-->T mutation (Asp-816-Val). After discontinuation of SCF the MC
      hyperplasia resolved confirming its reactive nature. Based on our case and
      similar cases mimicking mastocytosis, it seems of importance to apply recently
      established SM criteria in order to discriminate between reactive MC hyperplasia
      and true mastocytosis with certainty.

PMID- 12002762
TI  - The prognostic significance of trisomy 8 in patients with acute myeloid leukemia.
AB  - Recent therapeutic outcomes for patients with acute myeloid leukemia and trisomy
      8 (+8) who were seen at our institution were investigated. Complete remission was
      achieved in 85% with isolated +8, 100% with +8 and chromosomal abnormalities
      predictive of a favorable outcome, and 47% of patients with +8 and other, mostly
      complex chromosomal abnormalities. Median relapse-free and overall survivals in
      months were 5.5 and 12 (isolated +8), 20 and 25 (+8 and favorable karyotype), and
      7.5 and 6 (+8 and unfavorable karyotype). Despite an encouraging rate of complete
      remission, the relapse-free and overall survivals for patients with isolated +8
      were not significantly different from those of patients with +8 and unfavorable
      karyotypes. The presence of +8 did not appear to adversely affect the outcome of
      patients with favorable karyotypes.

PMID- 12002763
TI  - Central nervous system relapse of systemic non-Hodgkin's lymphoma: results of
      treatment based on high-dose methotrexate combination chemotherapy.
AB  - The objective of this study was to evaluate the feasibility and possible response
      to pre-radiation chemotherapy given to patients with central nervous system (CNS)
      relapse of systemic non-Hodgkin's lymphoma (NHL). Twenty-three consecutive adult
      patients with systenic NHL and first CNS relapse were evaluated by CSF cytology
      and neuroaxis MRI. Treatment was based on weekly high-dose methotrexate (HD-MTX)
      3.5 g/m2 and weekly intra-CSF cytarabine (ARA-C). Oral procarbazine 100 mg/m2
      days 2-15 was added to patients whose bone marrow reserve could tolerate this
      drug. Radiation therapy (RT) to the CNS was deferred in responding/stable CNS
      disease. All patients with leptomeningeal seeding, but without parenchymal
      involvement responded to treatment prior to RT with 33% achieving a complete
      response (CR). Concomitant response of systemic disease was noted in 36% of the
      cases with 9% CR. Addition of RT to the CNS did not significantly change the
      overall rate of CR. Progression free survival for CNS disease was 5 months and
      for systemic disease 2 months. All patients with parenchymal involvement
      responded to therapy prior to RT with only 9% achieving CR, and the addition of
      RT in these cases increased the rate of CR to 24%. In this group, three of four
      patients who had active systemic disease responded systemically. Progression free
      survival was 3 months for both CNS and systemic disease. The median survival of
      the whole group was 6 months; 1-year survival 32% and 2-year survival 15%. In
      conclusion, systemic HD-MTX-based combination chemotherapy yields an initial
      response rate of 100% in the CNS and a 47% concomitant systemic response. A
      complete CNS response can be obtained prior to RT but this adds little to the
      overall CR rate. Durable responses are rare. Since both CNS and systemic relapses
      appear in tandem, future trials should evaluate alternative modalities in order
      to enhance drug delivery into the CNS.

PMID- 12002764
TI  - Chromosomal and comparative genomic analyses of HHV-8-negative primary effusion
      lymphoma in five HIV-negative Japanese patients.
AB  - A rare subset of HIV lymphoma, known as primary effusion lymphoma (PEL), is a
      high-grade tumour carrying human herpes virus 8 (HHV-8). Very little is known
      about genomic aberration in PEL, and only a few HIV-negative PEL have been
      reported. Here we report the results of chromosomal analysis and comparative
      genomic hybridisation (CGH) conducted to detect regions of gain and loss, in five
      HIV-negative Japanese cases of HHV-8-negative PEL. All patients except one (35
      year-old female) were elderly men and the morphologic examination showed large
      cell type. PEL expressed B-cell-associated and activation-associated antigens,
      and exhibited clonal immunoglobulin genes. No HHV-8 was detected in all four
      examined cases, but Epstein-Barr virus (EBV) was detected in one case. Genomic
      abnormalities and aberrations were identified in all HHV-8/HIV-negative PEL. CGH
      studies showed gain in 19 of 24 chromosomes. Gains of 3q13-27, 8q24, 10q21-23 and
      Yq were detected in two of the five cases, but other gains were noted in each
      case. Chromosomal analysis revealed complex abnormalities both in numbers and
      structures. Burkitt lymphoma-associated t(8;22) was detected in one case, but +8
      chromosome and c-myc amplification were detected in the other three cases by
      Southern blot and/or fluorecence in situ hybridization (FISH). Abnormality of
      chromosome 8, which associates with c-myc, was detected in four of the five HHV
      8/HIV-negative PEL. However, the other common genomic abnormalities of HHV-8/HIV
      negative PEL were not detected in our study, but the complex abnormalities seemed
      to be true rather than the usual large B-cell lymphoma. Our results suggest that
      multi-step genomic abnormalities might be associated in HHV-8/HIV-negative PEL
      tumorigenesis.

PMID- 12002765
TI  - Extended survival in advanced-stage multiple myeloma patients treated with
      gallium nitrate.
AB  - Adjunctive anti-bone resorption therapy has become an important part of multiple
      myeloma (MM) treatment. Currently, no definite evidence exists that this therapy
      increases survival. We examined a cohort of 13 of 167 patients (8%) treated with
      the M-2 protocol who received adjuvant gallium nitrate (GN) treatment for
      osteolysis, and then compared the outcome of these patients to all individuals
      treated with the M-2 regimen. The stage at diagnosis was IA in two patients, IIIA
      in 10 patients and IIIB in one. Median age at diagnosis was 51 years (range 35
      73). Median (range) of entry data were: paraprotein level: 6000mg/dl (3058-8675);
      beta2M: 2.7mg/l, (1.2-9.6); LDH: 166U/l (142-237); hemoglobin: 10.2 g/dl (8.3
      12.6); albumin: 3.7 g/dl (2.5-5.0); calcium: 10.0 mg/dl (8.3-14.5); creatinine:
      1.2 mg/dl (0.7-2.7). Median survival in these patients was 87+ months from time
      of diagnosis compared with 48 months for all other patients treated on the M-2
      protocol. We identified a subgroup of patients with remarkably prolonged survival
      who had received M-2 chemotherapy and GN. Survival in this group markedly exceeds
      expectations for patients with advanced stage disease and poor prognostic
      features. The administration of GN may have a positive impact on survival either
      by decreasing skeletal complications or through a direct action of GN on the
      complex cytokine network involved in the proliferation of the malignant myeloma
      cell.

PMID- 12002766
TI  - Impact of early response to sequential high-dose chemotherapy on outcome of
      patients with advanced myeloma and poor prognostic features.
AB  - We report the results of a dose-intense chemotherapy regimen designed to rapidly
      induce remissions in patients with advanced multiple myeloma (MM). Patients
      received VAD for 3-6 cycles depending on response kinetics. This was followed by
      three sequential cycles of cyclophosphamide (CTX) at 3 g/m2 every 15 days with G
      CSF support. 71% of these patients had stage IIIa, 23% had renal failure. The
      median age was 58, median beta-2 microglobulin 4.6 and median albumin was 3.5,
      indicating poor prognosis. Of 35 patients, 66% achieved a complete response (CR)
      (SWOG). Six patients (18%) had a partial response. Fifty percent of the patients
      with renal failure recovered their kidney function. High-dose CTX contributed to
      tumor-mass reduction particularly in patients presenting with high-tumor burden.
      Tumor-mass reduction following three pulses of dexamethasone (4 days each) is
      significantly higher than with one pulse (p < 0.005). While high beta-2
      microglobulin and LDH levels (p < 0.05) were associated with poor outcome,
      patients who responded faster to chemotherapy had a longer survival (p = 0.005).
      We conclude that this regimen is safe and effective. A rapid response may be
      useful in selecting patients who may benefit from further high dose chemotherapy
      and stem cell support.

PMID- 12002767
TI  - CD19 expression and growth inhibition of tumours in human multiple myeloma.
AB  - Multiple myeloma (MM) is a proliferative disorder of monoclonal plasma cells
      which accumulate in human bone marrow (BM). CD19 is a hallmark differentiation
      antigen of the B cell lineage and positively regulates antigen receptor signal
      transduction in mature B cells. We have previously shown that malignant plasma
      cells (myeloma cells) isolated from the MM patients lack the CD19 expression,
      while non-malignant plasma cells isolated from the healthy donors do express the
      CD19 antigens. It is also intriguing that there exists both CD19- and CD19+
      plasma cells in some cases in pre-myeloma states including monoclonal gammopathy
      of undetermined significance (MGUS). It indicates that MGUS is usually composed
      of phenotypically non-malignant (CD19+) and malignant (CD19-) plasma cells.
      Furthermore, we recently demonstrate that, expression of the CD19 gene markedly
      inhibits the proliferation of human myeloma cell lines in vitro, and exhibits the
      reduced tumorigenicity in vivo and no anchorage-independent growth in vitro of a
      tumorigenic myeloma cell line. This inhibitory effect might result from the CD19
      mediated intracellular signals because it is not observed in cells expressing the
      mutant CD19, which lacks the cytoplasmic domain. In this review, we suggest that
      loss of CD19 in MM could contribute to the proliferative advantage of the
      malignant plasma cell clones in this disease. Furthermore, we propose the
      usefulness of the phenotypic analysis of plasma cells in human plasma cell
      dyscrasia as a new diagnostic tool, and the CD19 gene as a potential target for
      the gene therapy in MM.

PMID- 12002768
TI  - Mutational analyses of the AML1 gene in patients with myelodysplastic syndrome.
AB  - The AML1 gene is the most frequent target of translocations associated with human
      leukemias. We recently found somatic point mutations of the AML1 gene, V105ter
      and R139G, in two cases of myelodysplastic syndrome (MDS). Both mutations are
      present in the region encoding the Runt domain of AML1, and cause loss of the DNA
      binding ability of the resultant products. Of these mutants, V105ter has also
      lost the ability to heterodimerize with PEBP2beta/CBFbeta. On the other hand, the
      R139G mutant acts as a dominant negative inhibitor through competing with wild
      type AML1 for interaction with PEBP2beta/CBFbeta. In this review, we summarize
      mutational changes of the AML1 gene in hematological malignancies, especially in
      MDS and discuss the mechanism whereby the mutant acts as a dominant negative
      inhibitor of wild-type AML1.

PMID- 12002769
TI  - Serum soluble IL-6 receptor levels during the mobilization of stem cells to
      peripheral blood.
AB  - Serum soluble interleukin-6 receptors (sIL-6R) have been demonstrated to play an
      important role in hematopoiesis. We report here that serum sIL-6R levels reflect
      proliferative kinetics of the progenitors after stimulation by chemotherapy plus
      granulocyte colony-stimulating factor. Serum sIL-6R were serially evaluated in 26
      courses of peripheral blood (PB) stem cell collections in 16 patients using
      enzyme-linked immunosorbent assay. Expressions of IL-6R and CD34 on PB
      mononuclear cells were examined by flow cytometric analysis and expressions of IL
      6R mRNA were examined by reverse transcriptase polymerase chain reaction. There
      were no significant differences between the serum sIL-6R levels on day 0 in
      patients (27.8+/-2.1 ng/ml, mean +/- SEM) and those in controls (27.5+/-1.5
      ng/ml). Following chemotherapy the serum sIL-6R levels were significantly
      decreased, reaching a minimal level on day 14 (22.3+/-1.2 ng/ml, p < 0.01) and
      then significantly increased to above the baseline levels on day 21 (32.0+/-2.1
      ng/ml, p < 0.01). Similar oscillations in the number of white blood cells, IL6R+
      cells, CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) in PB
      could be observed and the peak expression of mRNA was compatible with the
      expression of antigen. Serum sIL-6R levels on day 17 and 19 were positively
      correlated with the number of CD34+ cells, IL-6R+ cells, CFU-GM in PB and the
      number of collected CD34+ cells in leukapheresis products. In addition, when
      comparing the 2 groups divided by the number of prior chemotherapies, the status
      of disease or dose of the mobilizing regimen, the serum sIL-6R levels were
      significantly increased after day 17 in the group that received fewer courses of
      prior chemotherapy, the group in complete remission and the group of high-dose
      chemotherapy. These findings indicated that sIL-6R levels do not reflect the
      hematopoietic ability in the steady state, or the capability of the hematopoiesis
      after stimulation. Thus, sIL-6R levels may be a marker for the timing of PBSC
      collection or the prediction of the number of collected CD34+ cells.

PMID- 12002770
TI  - Induction of human herpesvirus 8 gene expression in a posttransplantation primary
      effusion lymphoma cell line.
AB  - Human herpesvirus 8 (HHV-8 or Kaposi's sarcoma herpesvirus) is a gamma
      herpesvirus that is most likely the etiologic agent of both Kaposi's sarcoma and
      primary effusion lymphoma (PEL), a rare HIV-associated lymphoma. The role of HHV
      8 in post-transplant lymphoma is less well characterized. We demonstrate that HHV
      8 is constitutively present in LH5-21 cells, an atypical patient derived
      posttransplant PEL cell line. LH5-21 cells lack detectable Epstein-Barr virus,
      express T cell-associated surface markers and have undergone immunoglobulin heavy
      chain gene rearrangement. Incubation with 12-O-tetradecanoyl-phorbol- 13-acetate
      or butyrate induces high levels of several HHV-8 encoded genes that are
      associated with lytic replication. The patient from whom this cell line was
      derived demonstrated a dramatic clinical response to withdrawal of
      immunosuppressive therapy. While HHV-8 associated PELs in the post-transplant
      setting are rare, this study suggests that improvement in the host immunologic
      function might help in the management of some PELs.

PMID- 12002771
TI  - Bone morphogenetic protein (BMP)-2 induces apoptosis in human myeloma cells.
AB  - BMPs (bone morphogenetic proteins), members of the transforming growth factor
      (TGF)-beta superfamily, are a group of related proteins which are capable of
      inducing the formation of cartilage and bone, but are now regarded as
      multifunctional cytokines. However, little is known about their role in
      hematopoiesis. Recently, we found a novel function of BMPs to hematopoietic cells
      in that BMP-2 induces apoptosis not only in human myeloma cell lines, but also in
      primary samples from patients with multiple myeloma in vitro. BMP-2 caused cell
      cycle arrest in the G1 phase which was associated with accumulation of
      p21CIP1/WAF1 and p27KIP1, and the subsequent apoptosis of myeloma cells. Further
      analysis showed that BMP-2 induced down-regulation of Bcl-X(L) through the
      inactivation of STAT3, resulting in the induction of apoptosis in myeloma cells.
      We conclude that BMP-2 may have the potential to be one of the novel therapeutic
      agents for treatment in patients with multiple myeloma because of the beneficial
      effects on both myeloma cells and bone diseases. In this review, we summarize
      data concerning BMPs and BMP-2-induced apoptosis of myeloma cells including our
      own recent experimental data.

PMID- 12002772
TI  - Meningeal relapse after double peripheral blood stem cell transplantation in IgD
      myeloma.
AB  - A 54-year-old man diagnosed with IgD myeloma (stage IIIA) in complete remission
      (CR) received peripheral blood stem cell transplantation (PBSCT) twice with an
      interval of 4 months using high-dose melphalan 200mg/m2. However 9 months after
      the second PBSCT, he was readmitted because of lumbago, lower left hemiparesis,
      speech disturbance and left facial nerve palsy. A lumbar puncture revealed
      myeloma cells in the cerebrospinal fluid (CSF). The patient did not respond to
      any salvage chemotherapy and died of sepsis 27 months after the initial
      diagnosis. The findings in this patient suggest that another treatment modality
      including prophylactic intrathecal injection of an anti-cancer drug as well as
      allogeneic cell therapy is probably necessary in patients with high-risk IgD
      myeloma.

PMID- 12002773
TI  - Effective treatment of simultaneous small cell lung cancer and B-cell lymphoma.
AB  - Malignant lymphomas have been reported previously to coincide with
      adenocarcinomas of the stomach and, rarely, the kidney, breast, colon, liver, or
      lung. Here, we describe the first case to our knowledge of a malignant lymphoma
      and an extensive disease small cell cancer of the lung. A 60-year-old male was
      admitted for severe back pain and was found to have multiple enlarged lymph
      nodes, hepatosplenomegaly, and bilateral pleural effusions. A B-cell non
      Hodgkin's lymphoma (NHL) was diagnosed from biopsies of the stomach and liver.
      Further staging revealed a dense infiltration of the bone marrow by both a small
      cell lung cancer and a malignant lymphoma. Both tumors responded well to
      chemotherapy. This unique case report demonstrates that the simultaneous
      occurrence of small cell lung cancers and malignant lymphomas is extremely rare
      and may effectively be treated with chemotherapy.

PMID- 12002774
TI  - Coexistence of chronic neutrophilic leukemia with multiple myeloma.
AB  - A case report of simultaneous presentation of chronic neutrophilic leukemia and
      multiple myeloma (IgG kappa) in a 71-year-old male is described. The patient
      showed mature neutrophilic leukocytosis, hepatosplenomegaly, high neutrophil
      alkaline phosphatase score, hyperuricemia, neutrophils with toxic granulation and
      Dohle bodies, absence of Philadelphia chromosome and of the bcr-abl fusion gene.
      Moreover, a monoclonal IgG kappa paraproteinemia (36.93 g l(-1)) was detected.
      Bence-Jones proteinuria was 3.84 g l(-1). The bone marrow was grossly
      hypercellular with marked myeloid hyperplasia and aggregates of plasma cells. The
      patient died of severe bronchopneumonia after the transformation of chronic
      neutrophilic leukemia to acute myelomonocytic leukemia, 1.5 years following
      diagnosis.

PMID- 12002775
TI  - Successful unrelated cord blood transplantation for relapse after autologous
      transplantation in non-Hodgkin's lymphoma.
AB  - We report a 34-year-old male with relapsed non-Hodgkin's lymphoma (NHL) after
      autologous peripheral blood stem cell transplantation successfully treated with
      unrelated cord blood transplantation (CBT). The conditioning regimen included 12
      Gy total body irradiation and cyclophosphamide. After the conditioning, a total
      of 3.14 x 10(7)/kg cord blood nucleated cells was infused on 14 February 2000. An
      absolute neutrophil count greater than 5 x 10(8)/l and a self-sustained platelet
      count greater than 50 x 10(9)/l were achieved on days 21 and 43, respectively.
      During the follow up period, grade I acute graft-versus-host disease (GVHD) and
      limited chronic GVHD occurred, but both were successfully treated with a dose
      modification of cyclosporine. After a follow-up period of 16 months, the patient
      is alive and free of disease. To our knowledge this is the first report of a
      successful unrelated CBT for an adult NHL patient who relapsed after autologous
      transplantation.

PMID- 12002776
TI  - Prior invasive pulmonary and cerebellar mucormycosis is not a primary
      contraindication to perform an autologous stem cell transplatation in leukemia.
AB  - Mucormycosis infections, caused by fungi of the families Rhizopus, Mucor or
      Absidia, are typically rapidly progressive and often fatal. We report a 27-year
      old male with acute myeloid leukemia (AML) developing an invasive pulmonary-CNS
      mucormycosis during the neutropenic period after salvage induction chemotherapy;
      the infection was successfully controlled with surgery and antifungal therapy.
      The patient received two courses of consolidation chemotherapy and underwent
      autologous stem cells transplantation (ASCT) while receiving secondary antifungal
      systemic prophylaxis with liposomal Amphotericin B (L-AMB, Ambisome). There was
      no clinical, radiological or microbiological evidence of mycotic reactivation
      during the bone marrow transplantation (BMT) procedure.

PMID- 12002777
TI  - Nephrotic syndrome associated with agnogenic myeloid metaplasia.
AB  - Extramedullary hematopoiesis being an important feature of agnogenic myeloid
      metaplasia (AMM), a chronic myeloproliferative disease of clonal origin, may
      affect the kidneys, but this condition is usually asymptomatic. Until now, there
      is only one reported case of nephrotic syndrome associated with AMM. We present a
      patient with AMM who had nephrotic syndrome and whose renal biopsy revealed
      membranous glomerulonephritis together with renal extramedullary hematopoiesis.

PMID- 12002778
TI  - Life threatening acute epiglottitis in acute leukemia.
AB  - We report an 8-year-old boy who developed a life-threatening acute epiglottitis
      during induction chemotherapy for acute promyelocytic leukemia. He survived the
      infection with emergency tracheostomy, treatment with broad spectrum antibiotics
      and amphotericin, and the use of granulocyte-macrophage colony stimulating
      factor. No organism was identified. A literature review identified 18 cases of
      acute epiglottitis in cancer patients. Sixteen of them were suffering from
      hematologic malignancies and three patients had received bone marrow
      transplantation. Unlike the usual case of epiglottitis, the majority (15 out of
      18) of affected patients were adults and none of the infections was associated
      with Haemophilus influenzae. Streptococcus pneumoniae and Candida albicans were
      the most frequently identified pathogens. Early recognition and aggressive
      supportive care are required for successful management.

PMID- 12002779
TI  - Fatal airway obstruction caused by invasive aspergillosis of the thyroid gland.
AB  - Invasive aspergillosis is a common form of fungal infection in patients with
      hematological malignancies. Because Aspergillus species have angioinvasive
      properties, they frequently disseminate from the lung to a variety of organs via
      hematogenous spread. Extra-pulmonary involvement occurs at an advanced stage of
      invasive aspergillosis, and represents an ominous sign. However, few reports have
      been published on extra-pulmonary involvement in cases of aspergillosis. Its
      clinical features have not been fully clarified. We experienced a patient who
      developed thyrotoxicosis and fatal airway obstruction caused by invasive
      aspergillosis of the thyroid. A 26-year-old man was admitted to our hospital for
      the treatment of non-Hodgkin's lymphoma. During myelosuppression following the
      chemotherapy, he developed cervical swelling and hyperthyroidism. We suspected
      lymphoma infiltration to the thyroid, and irradiated it with a total of 26 Gy.
      However, the cervical lesion enlarged rapidly, and he complained of wheezing and
      dyspnea. We underwent immediate tracheostomy to secure the airway, but he died.
      Autopsy findings were striking. Extensive necrosis with diffuse infiltration of
      Aspergillus hyphae was observed in the thyroid gland. Necrotic tissues of the
      thyroid protruded into the tracheal lumen, causing airway obstruction. This case
      demonstrated that invasive aspergillosis of the thyroid can lead to medical
      emergency.

PMID- 12002780
TI  - Idiopathic myelofibrosis associated with primary biliary cirrhosis.
AB  - A patient with primary biliary cirrhosis (PBC) who developed idiopathic
      myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by
      liver biopsy, performed after a 2-month history of constitutional symptoms
      associated with abnormalities of the serum liver enzymes, with typical serum
      immunological markers being found. Although a favorable response of PBC to
      prednisone was observed, one and a half year later the patient developed anemia
      with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic
      picture, and IM was diagnosed by bone marrow biopsy. A few months later, a rapid
      worsening of the patient's clinical condition was noted, with an increase in the
      constitutional symptoms and need for frequent packed RBC transfusions, and she
      finally died from an infectious complication. This case represents a new
      association of IM with an autoimmune disease, supporting the hypothesis of a
      possible immune basis of IM in some cases.

PMID- 12002781
TI  - Teaching cases from the Royal Marsden and St Mary's Hospitals case 21: abnormal
      circulating lymphoid cells in a patient with an intestinal T-cell lymphoma
      associated with coeliac disease.

PMID- 12002782
TI  - Relapse of acute promyelocytic leukemia after 10 years long-term remission.

PMID- 12002783
TI  - AA-type amyloid tumor as an unsuspected cause of residual mass in a patient with
      large B-cell non-Hodgkin's lymphoma.
AB  - Amyloidosis is a rare complication of non-Hodgkin's lymphoma (NHL). AL amyloid
      deposits are usually localized in areas adjacent to the lymphoma, despite the
      presence of circulating light chains. However, AA-type amyloidosis is extremely
      unfrequent as a residual mass in patients with NHL. We report a case with diffuse
      large B-cell non-Hodgkin's lymphoma in which a residual tumoral mass
      corresponding to AA-type amyloidosis was found.

PMID- 12002784
TI  - Steroid hormone receptors and dietary ligands: a selected review.
AB  - Members of the nuclear steroid hormone superfamily mediate essential
      physiological functions. Steroid hormone receptors (SHR) act directly on DNA,
      regulate the synthesis of their target genes and are usually activated by ligand
      binding. Both endogenous and exogenous compounds and their metabolites may act as
      activators of SHR and disruptors of endocrine, cellular and lipid homeostasis.
      The endogenous ligands are generally steroids such as 17beta-oestradiol,
      androgens, progesterone and pregnenolone. The exogenous compounds are usually
      delivered through the diet and include non-steroidal ligands. Examples of such
      ligands include isoflavanoids or phytooestrogens, and food contaminants such as
      exogenous oestrogens from hormone-treated cattle, pesticides, polychlorinated
      biphenyls and plasticisers. Certain drugs are also ligands; so nuclear receptors
      are also important drug targets for intervention in disease processes. The
      present review summarises recent reports on ligand-activated SHR that describe
      the selective regulation of a tightly-controlled cross-talking network involving
      exchange of ligands, and the control of major classes of cytochrome P450 (CYP)
      isoforms which metabolise many bioactive exogenous compounds. Many CYP have broad
      substrate activity and appear to be integrated into a coordinated metabolic
      pathway, such that whilst some receptors are ligand specific, other sensors may
      have a broader specificity and low ligand affinity to monitor aggregate levels of
      inducers. They can then trigger production of metabolising enzymes to defend
      against possible toxic nutrients and xenobiotic compounds. The influence of
      dietary intakes of nutrients and non-nutrients on the human oestrogen receptors
      (alpha and beta), the aryl hydrocarbon receptor, the pregnane X receptor, the
      constitutive androstane receptor, and the peroxisome proliferator-activated
      receptors (alpha and gamma), can be examined by utilising computer-generated
      molecular models of the ligand-receptor interaction, based on information
      generated from crystallographic data and sequence homology. In relation to
      experimental and observed data, molecular modelling can provide a scientifically
      sound perspective on the potential risk and benefits to human health from dietary
      exposure to hormone-mimicking chemicals, providing a useful tool in drug
      development and in a situation of considerable public concern.

PMID- 12002785
TI  - The use of food consumption data in assessments of exposure to food chemicals
      including the application of probabilistic modelling.
AB  - Emphasis on public health and consumer protection, in combination with
      globalisation of the food market, has created a strong demand for exposure
      assessments of food chemicals. The food chemicals for which exposure assessments
      are required include food additives, pesticide residues, environmental
      contaminants, mycotoxins, novel food ingredients, packaging-material migrants,
      flavouring substances and nutrients. A wide range of methodologies exists for
      estimating exposure to food chemicals, and the method chosen for a particular
      exposure assessment is influenced by the nature of the chemical, the purpose of
      the assessment and the resources available. Sources of food consumption data
      currently used in exposure assessments range from food balance sheets to detailed
      food consumption surveys of individuals and duplicate-diet studies. The fitness
      for-purpose of the data must be evaluated in the context of data quality and
      relevance to the assessment objective. Methods to combine the food consumption
      data with chemical concentration data may be deterministic or probabilistic.
      Deterministic methods estimate intakes of food chemicals that may occur in a
      population, but probabilistic methods provide the advantage of estimating the
      probability with which different levels of intake will occur. Probabilistic
      analysis permits the exposure assessor to model the variability (true
      heterogeneity) and uncertainty (lack of knowledge) that may exist in the exposure
      variables, including food consumption data, and thus to examine the full
      distribution of possible resulting exposures. Challenges for probabilistic
      modelling include the selection of appropriate modes of inputting food
      consumption data into the models.

PMID- 12002786
TI  - Fine and ultrafine particles of the diet: influence on the mucosal immune
      response and association with Crohn's disease.
AB  - Crohn's disease is a modern Western disease characterised by transmural
      inflammation of the gastrointestinal tract. It is of unknown aetiology, but
      evidence suggests that it results from a combination of genetic predisposition
      and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are
      potent adjuvants in model antigen-mediated immune responses and are increasingly
      associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in
      macrophages of human gut-associated lymphoid tissue where the earliest signs of
      lesions in Crohn's disease are observed. Dietary microparticles are of endogenous
      or exogenous origin. Endogenous microparticles dominate and are calcium phosphate
      (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal
      gastrointestinal tract due to secretion of Ca and phosphate in the succus
      entericus. Exogenous dietary microparticles are contaminants (soil and/or dust)
      and food additives. TiO2, for example, is a food colourant, and aluminosilicates
      are anti-caking agents, although some aluminosilicates occur as natural
      contaminants. Food additives alone account for ingestion of approximately 10(12)
      particles/person per d. Possible mechanisms for the role of exogenous and
      endogenous dietary microparticles in promoting toleragenic or immune responses of
      gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised
      pilot study we have shown that a diet low in Ca and exogenous microparticles
      appears to alleviate the symptoms of ileal Crohn's disease, with a significant
      (P= 0.002) improvement in the Crohn's disease activity index. A multi-centre
      trial and further mechanistic studies at the cellular level are underway.

PMID- 12002787
TI  - The paradox of improved antiretroviral therapy in HIV: potential for nutritional
      modulation?
AB  - Chronic infection with HIV type 1 is associated with alterations in macronutrient
      metabolism, specifically elevated plasma lipids, glucose and reduced insulin
      sensitivity. These alterations are most severe in patients at the later stages of
      AIDS, indicating a relationship with disease progression. Recently, a metabolic
      syndrome, termed lipodystrophy, has been described in successfully-treated HIV
      patients in whom the altered macronutrient metabolism of HIV infection appears to
      be amplified markedly, with concurrent alterations in adipose tissue patterning.
      This syndrome presents a paradox, as before the development of highly-active
      antiretroviral therapy (HAART) the most severe perturbations in metabolism were
      observed in the sickest patients. Now, the patients that respond well to therapy
      are showing metabolic perturbations much greater than those seen before. The
      implications of this syndrome are that, whilst life expectancy may be increased
      by reducing viral load, there are concomitant increases in the risk of
      cardiovascular disease, diabetes and pancreatitis within this patient population.
      The aetiology of the syndrome remains unclear. In a collaborative trial with the
      Chelsea and Westminster Hospital in London we have used stable-isotope-labelled
      fatty acids to examine the hypothesis that treatment with HAART causes a delayed
      clearance of dietary lipid from the circulation, resulting in the retention of
      lipid within plasma and the downstream changes in insulin and glucose
      homeostasis. This hypothesis would indicate a role for low-fat diets, exercise
      and drugs that reduce plasma lipid or insulin resistance, in modulating the
      response to antiretroviral therapy in HIV infection.

PMID- 12002788
TI  - Salivary antioxidants and periodontal disease status.
AB  - Periodontal disease is a common chronic adult condition. The bacterium
      Porphyromonas gingivalis has been implicated in the aetiology of this disease,
      which causes destruction of the connective tissue and bone around the root area
      of the tooth. It has been observed that invading P. gingivalis bacteria trigger
      the release of cytokines such as interleukin 8 and tumour necrosis factor a,
      leading to elevated numbers and activity of polymorphonucleocytes (PMN). As a
      result of stimulation by bacterial antigens, PMN produce the reactive oxygen
      species (ROS) superoxide via the respiratory burst as part of the host response
      to infection. Patients with periodontal disease display increased PMN number and
      activity. It has been suggested that this proliferation results in a high degree
      of ROS release, culminating in heightened oxidative damage to gingival tissue,
      periodontal ligament and alveolar bone. Antioxidant constituents in plasma have
      been well-documented, being chiefly ascorbate, albumin and urate, and these are
      known to display sensitivity to dietary antioxidant intakes. The concentration of
      antioxidants in saliva does not appear to mirror those of plasma. The extent of
      dietary influence upon salivary antioxidant status is unclear. Urate is the
      predominant salivary antioxidant, with albumin and ascorbate providing minor
      contributions. Previous research has found reduced salivary antioxidant activity
      in patients suffering from periodontal disease. An improved understanding of the
      role antioxidants play in periodontitis, and the influence of nutrition on
      antioxidant status, may lead to a possible nutritional strategy for the treatment
      of periodontal disease.

PMID- 12002789
TI  - Nutritional losses and gains during processing: future problems and issues.
AB  - Developments in food technology and nutrition today are shaping our food supply
      in an unprecedented way. They have not only helped produce a variety of foods
      with varying taste and texture but also optimally retain the nutritional quality
      of food. Increased use of novel ingredients in the future manufacture of foods is
      likely to reduce the amount of micronutrients available in our diet. To combat
      this, food fortification may be more widely used. Collaboration between food
      technologists and nutritionists is imperative if we are to see the continued
      manufacture of wholesome food.

PMID- 12002790
TI  - Nutritional quality of organic food: shades of grey or shades of green?
AB  - Consumer concern regarding possible adverse health effects of foods produced
      using intensive farming methods has led to considerable interest in the health
      benefits of organically-produced crops and animal products. There appears to be
      widespread perception amongst consumers that such methods result in foods of
      higher nutritional quality. The present review concludes that evidence that can
      support or refute such perception is not available in the scientific literature.
      A limited number of studies have compared the nutrient compositions of
      organically- and conventionally-produced crops, with a very small number of
      studies that have compared animal products (meat, milk and dairy products)
      produced under the two agricultural systems. Very few compositional differences
      have been reported, although there are reasonably consistent findings for higher
      nitrate and lower vitamin C contents of conventionally-produced vegetables,
      particularly leafy vegetables. Data concerning possible impacts on animal and
      human health of diets comprising organic or conventional produce are extremely
      sparse. Data from controlled studies in animal models, particularly within single
      species, are limited or poorly designed, and findings from these studies provide
      conflicting conclusions. There are no reports in the literature of controlled
      intervention studies in human subjects. Comparison of health outcomes in
      populations that habitually consume organically- or conventionally-produced foods
      are flawed by the large number of confounding factors that might contribute to
      any differences reported. If consumer perceptions regarding potential health
      benefits of organic foods are to be supported, more research of better quality is
      needed than that which is currently available.

PMID- 12002791
TI  - Genetically modified foods, science, consumers and the media.
AB  - In contrast to the situation in the USA, where a wide range of genetically
      modified (GM) foods is available, in Europe very few GM products have been
      approved for marketing as foods, and there is widespread public concern about
      their safety and environmental impact. The marketing of a GM crop for food use in
      Europe falls under the EC novel foods regulations, and applications require the
      submission of an extensive dossier of information. The safety evaluation of GM
      foods presents considerable problems both in the conduct and interpretation of
      experimental studies, because conventional toxicity tests used in the evaluation
      of simple chemicals may not be appropriate for whole foods. To rationalise the
      safety evaluation process and to circumvent the difficulties in toxicological
      assessment of food materials, the concept of substantial equivalence has been
      developed. The concept is that if it can be demonstrated that the novel food is
      essentially similar to its conventional counterpart in terms of critical
      nutritional or anutritional components, then it is likely to be no more or less
      toxic than the latter. The possible introduction of unintended effects by the
      genetic modification process is particularly problematic for the safety
      evaluation process. The new genomic and post-genomic techniques are potentially
      valuable in the safety evaluation of GM foods, although they are as yet in their
      infancy.

PMID- 12002792
TI  - Overweight, obesity and physical activity levels in Irish adults: evidence from
      the North/South Ireland food consumption survey.
AB  - In the present paper the prevalence of obesity (BMI > or = 30 kg/m2) and current
      physical activity levels in Irish adults have been evaluated. The prevalence of
      obesity in Irish adults is currently 18%, with men at 20% and women at 16%. A
      further 47% of men and 33% of women are overweight (BMI 25.0-29.9 kg/m2). Since
      1990, obesity has more than doubled in men from 8% to 20%, and increased from 13%
      to 16% in women. The highest prevalence of obesity (30%) was found in women aged
      51-64years. Defined waist circumference action levels identified 48% of the
      population who are in need of weight management and who also are at a 1.5-4.5
      times increased risk of having at least one cardiovascular disease risk factor.
      Physical activity levels were low overall. Men were more active in work and
      recreational pursuits than women, but women were more active in household
      activities. Walking was the most popular recreational pursuit. However, TV
      viewing occupied most of the leisure time of men and women. Higher levels of
      activity were associated with a lower BMI and waist circumference. The results
      indicate the need for sensitive and individualised strategies to promote physical
      activity and to achieve a healthy weight status.

PMID- 12002793
TI  - Mad cows, mad corn and mad communities: the role of socio-cultural factors in the
      perceived risk of genetically-modified food.
AB  - The rapid globalization of the world economy has increased the need for a
      knowledge base of reliable socio-cultural differences in perceptions, values and
      ways of thinking about new food technologies. Awareness of socio-cultural
      differences is important because collaborative efforts to deal with food hazards
      presuppose some understanding of where, how and why the viewpoints of various
      stakeholders may differ. In the present paper factors that influence public
      perceptions of genetically-modified (GM) food are discussed, with a special focus
      on the unique circumstances of populations in the USA, Europe and developing
      countries. It is argued that effective communication and decision making about
      the risk of GM food depends critically on understanding how socio-cultural groups
      differ in their values and in the way they deal with the risks and benefits of
      new technologies. The implications of psychological aspects of perceived risk
      (including the roles of qualitative dimensions of risk, world views and trust)
      for public acceptance of new food technologies are highlighted.

PMID- 12002794
TI  - Food allergen avoidance: risk assessment for life.
AB  - The skills and knowledge required to carry out food allergen avoidance are
      becoming increasingly sophisticated. It is not enough to know the names of a
      handful of dishes which contain a known allergen as an ingredient. Many
      lifestyles now depend on food prepared away from the home. New product
      development has introduced a wide range of ingredients and dishes which are
      labour saving, exciting and innovative. Product traceability now depends on
      advanced technological support as it struggles to keep up with foods
      manufactured, prepared and served in ever more complex circumstances. Consumers
      are now faced with 'a jungle of choices'. However, those individuals who need to
      avoid a known allergen, particularly in trace quantities, often find that the
      food choice deemed suitable is poor, and the information available inadequate or
      even dangerously misleading. There are two important groups for whom this
      situation is a major concern. Thousands of families with young children are
      forced to live with the possibility that everyday foods may be contaminated by a
      known allergen which could kill in minutes. They live on their nerves, reading
      every packet and resorting to hyperprotective childcare and vigilance. In
      addition, the youngest independent consumers, teenagers and those in their
      twenties, may have little first-hand experience of food preparation. They may be
      ill-equipped in food-allergen risk assessment. Sadly, those who die from
      anaphylaxis or allergen-triggered asthma are often in this age-group. Current
      initiatives to support consumers at risk include a recognised standard for
      manufacturers seeking to eliminate an allergen from their production, and the
      integration of food allergy into training for caterers and food standards
      enforcement professionals.

PMID- 12002795
TI  - Nutrient insult in early pregnancy.
AB  - Nutrient insults in early pregnancy, such as nutrient deprivation during famines,
      are often associated with an unfavourable outcome. Suboptimal nutrition in the
      early stage of gestation has been linked to a number of adverse effects on fetal
      growth and development. Historically, nausea and vomiting in pregnancy (NVP) was
      an important contributor to pregnancy-related mortality; indeed, Charlotte Bronte
      died from starvation and dehydration after suffering very severe NVP 4 months
      into her first pregnancy (Gaskell, 1858). Although NVP seldom now progresses to
      be life-threatening, it affects the majority of pregnant women, and potentially
      presents a challenge to nutrient intake in the most vulnerable period of
      development. Symptoms range from mild (nausea only) to severe (a level of
      vomiting that restricts nutrient intake and ultimately threatens metabolic and
      electrolyte balance). Although NVP has been documented for thousands of years,
      its cause has not yet been satisfactorily elucidated, but seems to be related to
      endocrinological changes. Pregnant women also frequently report dietary cravings
      and aversions during pregnancy which can be linked to both the incidence and
      severity of NVP. Paradoxically, NVP appears to be positively associated with a
      favourable outcome of pregnancy, including increased birth weight and gestational
      age. The mechanisms by which NVP favours the outcome of pregnancy are not known.
      They may be related to women increasing their nutrient intake to alleviate
      symptoms, improving the quality of their diet or reducing energy expenditure.
      Alternatively, adaptation to a reduced nutrient intake might stimulate the
      expression of growth factors and affect placentation or metabolism, thus
      favouring fetal growth when NVP resolves.

PMID- 12002796
TI  - Dietary essential fatty acids and brain function: a developmental perspective on
      mechanisms.
AB  - Brain development is a complex interactive process in which early disruptive
      events can have long-lasting effects on later functional adaptation. It is a
      process that is dependent on the timely orchestration of external and internal
      inputs through sophisticated intra- and intercellular signalling pathways. Long
      chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and
      docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during
      development, and brain fatty acid (FA) composition reflects dietary availability.
      Membrane lipid components can influence signal transduction cascades in various
      ways, which in the case of LCPUFA include the important regulatory functions
      mediated by the eicosanoids, and extend to long-term regulation through effects
      on gene transcription. Our work indicates that FA imbalance as well as specific
      FA deficiencies can affect development adversely, including the ability to
      respond to environmental stimulation. For example, although the impaired water
      maze performance of mice fed a saturated-fat diet improved in response to early
      environmental enrichment, the brains of these animals showed less complex
      patterns of dendritic branching. Dietary n-3 FA deficiency influences specific
      neurotransmitter systems, particularly the dopamine systems of the frontal
      cortex. We showed that dietary deficiency of n-3 FA impaired the performance of
      rats on delayed matching-to-place in the water maze, a task of the type
      associated with prefrontal dopamine function. We did not, however, find an
      association over a wider range of brain DHA levels and performance on this task.
      Some, but not all, studies of human infants suggest that dietary DHA may play a
      role in cognitive development as well as in some neurodevelopmental disorders;
      this possibility has important implications for population health.

PMID- 12002797
TI  - Manipulating the sulfur amino acid content of the early diet and its implications
      for long-term health.
AB  - Epidemiological studies of human populations show that poor growth in utero
      predisposes an individual to the later development of type 2 (non-insulin
      dependent) diabetes mellitus and hypertension in adulthood. This phenomenon is
      not confined to man; feeding pregnant rats diets moderately deficient in protein
      has a similar effect, programming the adult blood pressure and glucose metabolism
      of the offspring. A restriction in the amino acid supply was thought to cause
      poor fetal growth. However, recent experiments have shown that this is not the
      case and instead have implicated the metabolism of the S-containing amino acids.
      Many semi-synthetic experimental diets contain an imbalance in S-containing amino
      acids, forcing the animal to synthesise a sizeable part of its cysteine
      requirement from methionine. Unfortunately, when the diet is low in protein, the
      oxidation of amino acids is reduced, perturbing methionine metabolism and
      increasing levels of homocysteine. It is this interaction between protein content
      and composition of the diet which influences neonatal viability and may also
      determine the long-term health of the offspring. An excess of homocysteine is
      known to affect levels of two of the main mediators of cellular methylation
      reactions, S-adenosyl methionine and methylene tetrahydrofolate. S-adenosyl
      methionine is the methyl donor for the methylation of newly-synthesised DNA,
      regulating chromatin assembly and gene expression. The balance between S-adenosyl
      methionine and the methylated derivatives of folic acid may be critical for the
      development of differentiating cells and the long-term regulation of gene
      expression.

PMID- 12002798
TI  - Early diet and growth: impact on ageing.
AB  - The modification of ageing by nutritional intervention is well recognised. Post
      weaning diet restriction is the only widely reproducible method to slow ageing,
      but the effects of prenatal and preweaning diet restriction have been less well
      characterised. There is some evidence that diet restriction instituted in utero
      or shortly after birth may have an opposite effect and be associated with
      increased ageing, and recent work suggests that it may shorten lifespan. Interest
      in this area has been rekindled by the growing body of epidemiological evidence
      showing that a number of age-related diseases are associated with poor growth and
      inadequate nutrition in early life. The relevance of this association to
      structural and functional ageing changes in different systems is now being
      considered. Work on musculo-skeletal ageing has demonstrated that loss of muscle
      strength and bone mass is greater in individuals who did not grow well in early
      life, and a range of studies suggests that maternal, developmental and
      nutritional factors are important. The underlying mechanisms remain speculative,
      and it remains to be determined whether they are system-specific or universal
      throughout the body. A new cohort of subjects aged between 60 and 70 years is
      being established to investigate how genetic factors interact with growth and
      nutritional influences to programme musculo-skeletal ageing in later life.

PMID- 12002799
TI  - The athlete's diet: nutritional goals and dietary strategies.
AB  - When talented, motivated and highly trained athletes meet for competition the
      margin between victory and defeat is usually small. When everything else is
      equal, nutrition can make the difference between winning and losing. Although the
      primary concern of many athletes is to supplement the diet with protein, vitamins
      and minerals, and a range of more exotic compounds, key dietary issues are often
      neglected. Athletes must establish their nutritional goals, and must also be able
      to translate them into dietary strategies that will meet these goals. Athletes
      are often concerned with dietary manipulations in the period around competition,
      but the main role of nutrition may be to support consistent intensive training
      which will lead to improved performance. Meeting energy demand and maintaining
      body mass and body fat at appropriate levels are key goals. An adequate intake of
      carbohydrate is crucial for maintaining muscle glycogen stores during hard
      training, but the types of food and the timing of intake are also important.
      Protein ingestion may stimulate muscle protein synthesis in the post-exercise
      period, promoting the process of adaptation in the muscles. Restoration of fluid
      and electrolyte balance after exercise is essential. If energy intake is high and
      a varied diet is consumed, supplementation of the diet with vitamins and minerals
      is not warranted, unless a specific deficiency is identified. Specific strategies
      before competition may be necessary, but this requirement depends on the demands
      of the sport. Generally, it is important to ensure high pre-competition glycogen
      stores and to maintain fluid balance. There is limited evidence to support the
      use of dietary supplements, but some, including perhaps creatine and caffeine,
      may be beneficial.

PMID- 12002800
TI  - An obesity clinic model.
AB  - The high incidence of obesity in Ireland is of growing concern. The Irish
      Universities Nutrition Alliance North/South Food Consumption Survey found that 18
      % of the population are obese and 39% overweight. Obesity and overweight increase
      the risk of developing CHD, type 2 diabetes, hypertension and some forms of
      cancer. It is well accepted that the best treatment for obesity is a combination
      of energy intake reduction and regular exercise. Previously, dietary compliance
      has been shown to improve when monitored on a regular basis. The lengthy delay
      between clinic visits to the dietitian has been reported by those who failed to
      lose weight to be the main reason for poor compliance. A weight monitoring clinic
      was designed to offer those requiring regular support and encouragement the
      opportunity to monitor their weights on a more regular basis, while waiting for
      their return visit to the dietitian in the Outpatient Departments. As resources
      were limited, an efficient use of time was essential. The clinic design was: 1
      h/week; eight to fourteen appointments per clinic; weekly or fortnightly visit;
      return patients only. The clinic was started on a trial basis in June 1999, and
      was evaluated in December 2000. Referrals were only taken from other dietitians,
      and each participant was informed in advance of the necessity of having a return
      Outpatient Department appointment for full dietary review. Forty-eight
      participants attended more than three times up to and including December 2000
      (seven males, forty-one females). The number of clinic visits ranged from three
      to twenty-eight. Mean weight at start of clinic was 92.94 kg. Of the group
      attending, 67 % (thirty-two) successfully lost weight and maintained this weight
      loss. This ranged from 0.1 kg to 23.5 kg. While in total 31% (fifteen) of
      attendees had gained weight at December 2000, all attendees, including this
      fifteen, had lost weight at some point during the clinic. Self-reported reasons
      given for weight regain included: (1) non-attendance at weight clinic (40%); (2)
      Christmas or holidays (13%); (3) stress related to family, work (13%); (4) ill
      health or medication (13%). The remaining 20% reported no reason. Other findings
      included better compliance with diet and improved overall balance. There was an
      overall improvement in other dietary-related problems, e.g. reduced cholesterol,
      improved glycaemic control, reduced blood pressure. The participants attending
      the clinic reported decreased clothes size and improved self-image and
      confidence. They were more enthusiastic about dietary compliance, and all
      attendees expressed their satisfaction with the clinic and the service.

PMID- 12002801
TI  - Evidence for consistent patterns between flavonoid structures and cellular
      activities.
AB  - A wide variety of plant-derived compounds, including the polyphenolic flavonoids,
      is present in the human diet or is consumed for medicinal reasons.
      Epidemiological and animal studies tend to suggest a protective effect of
      flavonoids against cardiovascular diseases and some types of cancer. Although
      flavonoids have been studied for about 50 years, the cellular mechanisms involved
      in their biological activity are still largely unknown. Antioxidant properties of
      the flavonoids have been postulated as a mechanism for putative protective effect
      against cardiovascular disease. Nevertheless, these properties alone are not
      sufficient to explain the anti-carcinogenic potential of these polyphenols. The
      mechanisms by which the molecules interact with cells or are absorbed by them are
      very important for determining the intracellular concentration and distribution
      of the metabolites to internal organs. With the exception of the cells lining the
      gastrointestinal tract, all other cells in the body are only exposed to flavonoid
      metabolites and degradation products. No previous studies have addressed this
      aspect of cellular exposure, except for some methylated metabolites. Within the
      last decade, reports on flavonoid activities have been largely associated with
      enzyme inhibition and anti-proliferative activity. From our recent work on the
      human colon cancer cell line HT29 and comparison with published studies,
      structure-function relationships demonstrate that antioxidant, enzyme inhibitor
      or anti-proliferative activities are dependent on particular structure motifs.
      The present review also presents a summary of mechanistic data on a few elected
      compounds.

PMID- 12002802
TI  - Vitamin K uptake in hepatocytes and hepatoma cells.
AB  - Hepatocellular carcinoma (HCC) or hepatoma cells have impaired ability to perform
      vitamin K-dependent carboxylation reactions. Vitamin K can also inhibit growth of
      HCC cells in vitro. Both carboxylation and growth inhibition are vitamin K dose
      dependent. We used rat hepatocytes, a vitamin K-growth sensitive (MH7777) and a
      vitamin K-growth resistant (H4IIE) rat hepatoma cell line to examine vitamin K
      uptake and vitamin K-mediated microsomal carboxylation. We found that vitamin K
      is taken up by normal rat hepatocytes against a saturable concentration gradient.
      The relative rates of uptake by rat hepatocytes and the two rat cell lines MH7777
      and H4IIE correlated with their sensitivity to vitamin K-mediated cell growth
      inhibition. Pooled hepatocytes from liver nodules from rats treated with the
      hepatocarcinogen diethylnitrosamine (DEN) also had a reduced rate of vitamin K
      uptake. However, using a cell-free system, microsomes from both normal rat
      hepatocytes and the two rat hepatoma cell lines had a similar ability to support
      carboxylation mediated by exogenously added vitamin K. The results support the
      hypothesis that different sensitivity of hepatoma cells to vitamin K may be due
      to differences in vitamin K uptake and may be unrelated to the actions of vitamin
      K on carboxylation.

PMID- 12002803
TI  - Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin
      turnover in rat brain.
AB  - Gamma-hydroxybutyrate (GHB) is both a therapeutic agent and a recreative drug. It
      has sedative, anxiolytic and euphoric effects. These effects are believed to be
      due to GHB-induced potentiation of cerebral GABAergic and dopaminergic
      activities, but the serotonergic system might also be involved. In this study, we
      examine the effects of pharmacological doses of GHB on the serotonergic activity
      in rat brain. Administration of 4.0 mmol/kg i.p. GHB to rats induces an
      accumulation of tryptophan and 5-HIAA (5-hydroxyindole acetic acid) in the
      frontal cortex, striatum and hippocampus without causing significant change in
      the tissue serotonin content. In the extracellular space, GHB induced a slight
      decrease in serotonin release. The tryptophan and 5-HIAA accumulation induced by
      GHB is mimicked by the GHB receptor agonist para-chlorophenyl
      transhydroxycrotonate (NCS-356) and blocked by NCS-382 (6,7,8,9-tetrahydro-5-[H]
      benzocycloheptene-5-ol-4-ylidene acetic acid) a selective GHB receptor
      antagonist. GHB induces the accumulation of either a derivative of or [3H]
      tryptophan itself in the extracellular space, possibly by increasing tryptophan
      transport across the blood-brain barrier. The blood content of certain neutral
      amino-acids, including tryptophan, is also increased by peripheral GHB
      administration. Some of the effect of GHB could be reproduced by baclofen and
      reduced by the GABAB antagonist CGP 35348. Taken together, these results indicate
      that the GHB-induced stimulation of tissue serotonin turnover may be due to an
      increase in tryptophan transport to the brain and in its uptake by serotonergic
      cells. As the serotonergic system may be involved in the regulation of sleep,
      mood and anxiety, the stimulation of this system by high doses of GHB may be
      involved in certain neuropharmacological events induced by GHB administration.

PMID- 12002804
TI  - Differences in the subcellular localization of alpha1-adrenoceptor subtypes can
      affect the subtype selectivity of drugs in a study with the fluorescent ligand
      BODIPY FL-prazosin.
AB  - G protein-coupled receptor (GPCR) subtypes are differentially distributed in the
      cell; however, it remains unclear how this affects the subtype selectivity of
      particular drugs. In the present study, we used flow cytometry analysis with the
      fluorescent ligand, BODIPY FL-prazosin, to study the relationship between the
      subcellular distribution of subtype receptors and the subtype-selective character
      of ligands using alpha1a and alpha1b-adrenoceptors (ARs). Alpha1a-ARs
      predominantly localize inside the cell, while alpha1b-ARs on the cell surface.
      Flow cytometry analysis and confocal laser-scanning micrographs of living cells
      showed that BODIPY FL-prazosin can label not only alpha1-ARs on the cell surface,
      but also those localized inside the cell. Furthermore, flow cytometry analysis of
      alpha1A-AR-selective drug, KMD-3213, and alpha1B-AR-selective drug, CEC, revealed
      that the major determinant of the subtype selectivity of each drug is different.
      The alpha1A-AR selectivity of KMD-3213 can be explained by its much higher
      affinity for alpha1a-AR than alpha1b-AR (affinity-dependent selectivity), while
      the alpha1B-AR selectivity of the hydrophilic alkylating agent CEC is due to
      preferential inactivation of alpha1-ARs on the cell surface (receptor
      localization-dependent selectivity). This study illustrates that factors in
      addition to the affinity of the drug for the receptor, such as subcellular
      localization of the receptor, should be taken into account in assessing the
      subtype selectivity of a drug.

PMID- 12002805
TI  - Activation of lung vagal sensory receptors by circulatory endotoxin in rats.
AB  - Although endotoxin is known to induce various pulmonary responses that are linked
      to the function of lung vagal sensory receptors, its effects on these pulmonary
      receptors are still not clear. This study investigated the effects of circulatory
      endotoxin on the afferent activity of lung vagal sensory receptors in rats. We
      recorded afferent activity arising from vagal pulmonary C fibers (CFs), rapidly
      adapting receptors (RARs), tonic pulmonary stretch receptors (T-PSRs), and phasic
      pulmonary stretch receptors (P-PSRs) in 64 anesthetized, paralyzed, and
      artificially ventilated rats. Intravenous injection of endotoxin (50 mg/kg;
      lipopolysaccharide) stimulated 7 of the 8 CFs, 8 of the 8 RARs, and 4 of the 8 T
      PSRs studied, while having no effect on the 8 P-PSRs tested. The stimulation
      started 3-16 min after endotoxin injection and lasted until the end of the 90-min
      observation period. The evoked discharge of either CFs or RARs was not in phase
      with the ventilatory cycle, whereas that of T-PSRs showed a respiratory
      modulation. Injection of a saline vehicle caused no significant change in the
      discharge of these receptors. Additionally, endotoxin significantly produced an
      increase in total lung resistance, and decreases in dynamic lung compliance and
      arterial blood pressure. Our results demonstrate that a majority of lung vagal
      sensory receptors are activated following intravenous injection of endotoxin, and
      support the notion that these pulmonary receptors may function as an important
      afferent system during endotoxemia.

PMID- 12002806
TI  - Effect of a mu-opioid receptor-selective antagonist on interleukin-6 fever.
AB  - The endogenous opioid system has been found to be involved in fever caused by
      pyrogens. Recent work in our laboratory has demonstrated that the mu-opioid
      receptor is involved in interleukin-1beta (IL-1beta)- and in lipopolysaccharide
      (LPS)-induced fevers. In the present study, we have investigated the role of the
      mu-opioid receptor in the preoptic anterior hypothalamus (POAH) in fever induced
      by interleukin-6 (IL-6). Following stereotaxic implantation of a guide cannula
      into the POAH for microinjection, radio transmitters to monitor body temperature
      (Tb) continuously were inserted intraperitoneally. Adult male Sprague-Dawley rats
      were microinjected with 0.5 microg of the selective mu-opioid receptor
      antagonist, cyclic D-phe-Cys-Try-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), into the POAH.
      Thirty min later, IL-6 (100 ng) was injected into the POAH. CTAP significantly
      blocked the IL-6 fever. CTAP alone had no effect on Tb during the 390-min
      recording period. These data indicate that mu-opioid receptors within the POAH
      mediate IL-6 fever and add to the increasing evidence that the opioid system is
      involved in the pathogenesis of fever in rats.

PMID- 12002808
TI  - Metabolism of [6]-gingerol in rats.
AB  - The metabolic fate of [6]-gingerol, one of the active constituents of Zingiber
      officinale Roscoe, was investigated using rats. The bile of rats orally
      administered [6]-gingerol was shown to contain a major metabolite (1) by HPLC
      analysis. Although the metabolites derived from [6]-gingerol were not detected in
      the urine, the ethyl acetate extract of the urine after enzymatic hydrolysis was
      shown to contain six minor metabolites (2-7). Their structures were determined to
      be (S)-[6]-gingerol-4'-O-beta-glucuronide (1), vanillic acid (2), ferulic acid
      (3), (S)-(+)-4-hydroxy-6-oxo-8-(4-hydroxy-3-methoxyphenyl) octanoic acid (4), 4
      (4-hydroxy-3-methoxyphenyl)butanoic acid (5), 9-hydroxy [6]-gingerol (6) and (S)
      (+)-[6]-gingerol (7) based on spectroscopic and chemical data. The total
      cumulative amount of 1 excreted in the bile and 2-7 in the urine during 60 h
      after the oral administration of [6]-gingerol were approximately 48% and 16% of
      the dose, respectively. The excretion of 2-7 in the urine decreased after gut
      sterilization. On the other hand, the incubations of [6]-gingerol with rat liver
      showed the presence of 9-hydroxy [6]-gingerol, gingerdiol (8), and (S)-[6]
      gingerol-4'-O-beta-glucuronide (1). These findings suggest that the gut flora and
      enzymes in the liver play an important part in the metabolism of [6]-gingerol.

PMID- 12002807
TI  - Comparison of angiotensin II (Ang II) effects in the internal anal sphincter
      (IAS) and lower esophageal sphincter smooth muscles.
AB  - Studies were performed to compare the actions of Ang II in the internal anal
      sphincter (IAS) vs. lower esophageal sphincter (LES) smooth muscles in vitro, in
      opossum and rabbit. Studies also were carried out in isolated smooth muscle
      cells. In opossum, Ang II produced no discernible effects in the IAS, but did
      produce a concentration-dependent contraction in the LES. Conversely, in the
      rabbit, while Ang II caused a modest response in the LES, it caused a significant
      contraction in the IAS. The contractile responses of Ang II in the opossum LES
      were mostly resistant to different neurohumoral antagonists but were antagonized
      by AT1 antagonist losartan. AT2 antagonist PD 123,319, rather than inhibiting,
      prolonged the contractile action of Ang II. The contractile actions of Ang II in
      the opossum LES were not modified by the tyrosine kinase inhibitors (genistein
      and tyrphostin 1 x 10(-6) M) but were partially attenuated by the PKC inhibitor H
      7 (1 x 10(-6) M), Ca2+ channel blocker nicardipine (1 x 10(-5) M), Rho kinase
      inhibitor HA-1077 (1 x 10(-7) M) or p(44/42) MAP kinase inhibitor PD 98059 (5 x
      10(-5) M). The combination of HA-1077 and H-7 did not cause an additive
      attenuation of Ang II responses. Western blot analyses revealed the presence of
      both AT1 and AT2 receptors. We conclude that Ang lI-induced contraction of
      sphincteric smooth muscle occurs primarily by the activation of AT1 receptors at
      the smooth muscle cells and involves multiple pathways, influx of Ca2+, and PKC,
      Rho kinase and p(44/42) MAP kinase.

PMID- 12002809
TI  - Antinociceptive activity of a novel buprenorphine analogue.
AB  - HS-599 is a didehydroderivative of buprenorphine that displays high affinity and
      good selectivity for mu-opioid receptors. We studied its antinociceptive
      properties after s.c. injection in mice with the tail-flick and hot-plate tests.
      In the tail-flick test HS-599 (AD50 = 0.2801 micromol/kg s.c.) behaved as a full
      agonist and was twice as potent as buprenorphine (AD50=0.4569 micromol/kg s.c.)
      and 50 times more potent than morphine (AD50 = 13.3012 micromol/kg s.c.). Whereas
      the mu-opioid receptor antagonists naloxone (1-10 mg/kg s.c.) and naltrexone (5
      15 mg/kg s.c.) antagonized HS-599 induced analgesia, the delta-opioid receptor
      antagonist naltrindole (20 mg/kg s.c.) and the kappa-opioid receptor antagonist
      nor-binaltorphimine (20 mg/kg s.c.) did not. With the hot-plate test at 50
      degrees C, HS-599 (AD50 = 0.0359 micromol/kg s.c.) was a full agonist about 130
      times more potent than morphine (AD50 = 4.8553 micromol/kg s.c.). With a high
      intensity nociceptive stimulus (55 degrees C) HS-599 (AD50 = 1.0382 micromol/kg
      s.c.) remained 7 times more potent than morphine (AD50 = 7.0210 micromol/kg s.c.)
      but never exceeded the 55% of the maximum possible effect, behaving as a partial
      agonist able to antagonize morphine antinociception in a dose-dependent manner.
      HS-599 promises to be a potent and safe new analgesic, preferentially acting at
      spinal level.

PMID- 12002810
TI  - cAMP inhibits cytokine-induced biosynthesis of tetrahydrobiopterin in human
      umbilical vein endothelial cells.
AB  - We studied the effects of cAMP on cytokine (interferon-gamma plus tumor necrosis
      factor-alpha)-induced stimulation of tetrahydrobiopterin (BH4) synthesis in human
      umbilical vein endothelial cells (HUVEC). The cytokine mixture caused a marked
      increase in the biosynthesis and release of BH4 by HUVEC. Dibutyryl-cAMP produced
      a dose-dependent inhibition of this cytokine-induced stimulation of synthesis and
      release of BH4 by these cells. 8-Bromo-cAMP also caused a significant inhibition,
      although the effects were less marked than those of dibutyryl-cAMP. Both
      forskolin and the stable analog of prostacyclin, iloprost, caused cAMP
      accumulation and a concomitant diminution of the cytokine-induced BH4 synthesis
      in HUVEC. Dibutyryl-cAMP and iloprost also significantly inhibited the cytokine
      induced stimulation of GTP cyclohydrolase I (GCHI) activity and mRNA production.
      We concluded that the suppression by the cAMP messenger system of cytokine
      induced stimulation of synthesis and release of BH4 by HUVEC can be attributed to
      the inhibition of the activity of GCHI, the rate-limiting enzyme in BH4
      biosynthetic pathway, in HUVEC. The data also suggest that the cAMP-mediated
      reduction in the GCHI mRNA level may at least partially explain the decline in
      GCHI activity. It is reasoned that under inflammatory conditions, cAMP-elevating
      agents such as prostacyclin exert regulatory effects on circulation by inhibiting
      cytokine-induced synthesis and release of BH4 by HUVEC.

PMID- 12002811
TI  - Effects of the NMDA antagonist MK-801 on radial maze performance in histidine
      deficient rats.
AB  - We examined the effects of a histidine-deficient diet on brain histamine contents
      as well as on learning and memory using the eight-arm radial maze in rats. A
      significant decrease in histamine content in the hippocampus was observed after
      long-term feeding of rats with a histidine-deficient diet. At the same time,
      significant enhancement of the acquisition process in radial maze performance was
      also observed. Pyrilamine did not show a significant effect on radial maze
      performance in histidine-deficient rats. On the other hand, pyrilamine caused a
      significant spatial memory deficit in control rats. Scopolamine was effective in
      inhibiting spatial memory in both histidine-deficient and control rats. MK-801
      caused spatial memory deficits more potently in histidine-deficient rats than in
      controls. Brain glycine contents showed a significant increase in the hippocampus
      in histidine-deficient rats. These results indicated that the spatial memory
      deficits induced by MK-801 in histidine-deficient rats are closely related to
      increased glycine levels and activation of NMDA receptors.

PMID- 12002812
TI  - Passive immunization against dental caries and periodontal disease: development
      of recombinant and human monoclonal antibodies.
AB  - Indigenous micro-organisms in the oral cavity can cause two major diseases,
      dental caries and periodontal diseases. There is neither agreement nor consensus
      as to the actual mechanisms of pathogenesis of the specific virulence factors of
      these micro-organisms. The complexity of the bacterial community in dental plaque
      has made it difficult for the single bacterial agent of dental caries to be
      determined. However, there is considerable evidence that Streptococcus mutans is
      implicated as the primary causative organism of dental caries, and the cell
      surface protein antigen (SA I/II) as well as glucosyltransferases (GTFs) produced
      by S. mutans appear to be major colonization factors. Various forms of
      periodontal diseases are closely associated with specific subgingival bacteria.
      Porphyromonas gingivalis has been implicated as an important etiological agent of
      adult periodontitis. Adherence of bacteria to host tissues is a prerequisite for
      colonization and one of the important steps in the disease process. Bacterial
      coaggregation factors and hemagglutinins likely play major roles in colonization
      in the subgingival area. Emerging evidence suggests that inhibition of these
      virulence factors may protect the host against caries and periodontal disease.
      Active and passive immunization approaches have been developed for immunotherapy
      of these diseases. Recent advances in mucosal immunology and the introduction of
      novel strategies for inducing mucosal immune responses now raise the possibility
      that effective and safe vaccines can be constructed. In this regard, some
      successful results have been reported in animal experimental models.
      Nevertheless, since the public at large might be skeptical about the seriousness
      of oral diseases, immunotherapy must be carried out with absolute safety. For
      this goal to be achieved, the development of safe antibodies for passive
      immunization is significant and important. In this review, salient advances in
      passive immunization against caries and periodontal diseases are summarized, and
      the biotechnological approaches for developing recombinant and human-type
      antibodies are introduced. Furthermore, our own attempts to construct single
      chain variable fragments (ScFv) and human-type antibodies capable of neutralizing
      virulence factors are discussed.

PMID- 12002813
TI  - Oro-facial gangrene (noma/cancrum oris): pathogenetic mechanisms.
AB  - Cancrum oris (Noma) is a devastating infectious disease which destroys the soft
      and hard tissues of the oral and para-oral structures. The dehumanizing oro
      facial gangrenous lesion affects predominantly children ages 2 to 16 years,
      particularly in sub-Saharan Africa, where the estimated frequency in some
      communities varies from 1 to 7 cases per 1000 population. The risk factors are
      poverty, malnutrition, poor oral hygiene, residential proximity to livestock in
      unsanitary environments, and infectious diseases, particularly measles and those
      due to the herpesviridae. Infections and malnutrition impair the immune system,
      and this is the common denominator for the occurrence of noma. Acute necrotizing
      gingivitis (ANG) and oral herpetic ulcers are considered the antecedent lesions,
      and ongoing studies suggest that the rapid progression of these precursor lesions
      to noma requires infection by a consortium of micro-organisms, with Fusobacterium
      necrophorum (Fn) and Prevotella intermedia (Pi) as the suspected key players.
      Additional to production of a growth-stimulating factor for Pi, Fn displays a
      classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin, and a hemolysin.
      Without appropriate treatment, the mortality rate from noma is 70-90%. Survivors
      suffer the two-fold afflictions of oro-facial mutilation and functional
      impairment, which require a time-consuming, financially prohibitive surgical
      reconstruction.

PMID- 12002814
TI  - Oral candidal infections and antimycotics.
AB  - The advent of the human immunodeficiency virus infection and the increasing
      prevalence of compromised individuals in the community due to modern therapeutic
      advances have resulted in a resurgence of opportunistic infections, including
      oral candidoses. One form of the latter presents classically as a white lesion of
      "thrush" and is usually easily diagnosed and cured. Nonetheless, a minority of
      these lesions appears in new guises such as erythematous candidosis, thereby
      confounding the unwary clinician and complicating its management. Despite the
      availability of several effective antimycotics for the treatment of oral
      candidoses, failure of therapy is not uncommon due to the unique environment of
      the oral cavity, where the flushing effect of saliva and the cleansing action of
      the oral musculature tend to reduce the drug concentration to sub-therapeutic
      levels. This problem has been partly circumvented by the introduction of the
      triazole agents, which initially appeared to be highly effective. However, an
      alarming increase of organisms resistant to the triazoles has been reported
      recently. In this review, an overview of clinical manifestations of oral
      candidoses and recent advances in antimycotic therapy is given, together with
      newer concepts, such as the post-antifungal effect (PAFE) and its possible
      therapeutic implications.

PMID- 12002815
TI  - Mouse submandibular gland morphogenesis: a paradigm for embryonic signal
      processing.
AB  - Signal processing is the sine qua non of embryogenesis. At its core, any single
      signal transduction pathway may be understood as classic Information Theory,
      adapted as an open system such that, because of networking, the "receiver" is
      presented with more information than was initially signaled by the "source". Over
      40 years ago, Waddington presented his "Epigenetic Landscape" as a metaphor for
      the hierarchical nature of embryogenesis. Mathematically, Waddington's landscape
      may be modeled as a neural net. The "black box" of the neural net is an
      interacting network of signal transduction pathways (using hormones, growth
      factors, cytokines, neurotransmitters, and others) which inform the Boolean logic
      gates. An emerging theme in developmental biology is that defined sets of
      epigenetic circuits are used in multiple places, at multiple times, for similar
      and sometimes different purposes during organogenesis. As we show here,
      submandibular gland embryonic and fetal development is a splendid paradigm of
      these epigenetic circuits and their phenotypic outcomes, such as branching and
      lumen formation.

PMID- 12002816
TI  - Role of saliva in the maintenance of taste sensitivity.
AB  - Saliva is the principal fluid component of the external environment of the taste
      receptor cells and, as such, could play a role in taste sensitivity. Its main
      role includes transport of taste substances to and protection of the taste
      receptor. In the initial process of taste perception, saliva acts as a solvent
      for taste substances; salivary water dissolves taste substances, and the latter
      diffuse to the taste receptor sites. During this process, some salivary
      constituents chemically interact with taste substances. For example, salivary
      buffers (e.g., bicarbonate ions) decrease the concentration of free hydrogen ions
      (sour taste), and there are some salivary proteins which may bind with bitter
      taste substances. Another effect of saliva on taste transduction is that some
      salivary constituents can continuously stimulate the taste receptor, resulting in
      an alteration of taste sensitivity. For example, the taste detection threshold
      for NaCl is slightly above the salivary sodium concentrations with which the
      taste receptor is continuously stimulated. In contrast, saliva protects the taste
      receptor from damage brought about by dryness and bacterial infection, and from
      disuse atrophy via a decrease in transport of taste stimuli to the receptor
      sites. This is a long-term effect of saliva that may be related to taste
      disorders. These various effects of saliva on the taste perception differ
      depending on the anatomical relationship between the taste buds and oral openings
      of the ducts of the salivary glands. Many taste buds are localized in the
      trenches of the foliate and circumvallate papillae, where the lingual minor
      salivary glands (von Ebner's glands) secrete saliva. Taste buds situated at the
      surface of the anterior part of the tongue and soft palate are bathed with the
      mixed saliva secreted mainly by the three major salivary glands.

PMID- 12002817
TI  - The role of serotonin and neurotransmitters during craniofacial development.
AB  - Several neurotransmitters, in particular serotonin (5-HT), have demonstrated
      multiple functions during early development and mid-gestational craniofacial
      morphogenesis. Early studies indicated that 5-HT is present in the oocyte, where
      it appears to function as a regulator of cell cleavage. Later, it has a
      significant role during gastrulation, during which there are significant areas of
      5-HT uptake in the primitive streak. Subsequently, in association with
      neurulation, 5-HT uptake is seen in the floor plate of the developing neural
      tube. During neural crest formation and branchial arch formation, 5-HT has been
      demonstrated to facilitate cell migration and stimulate cell differentiation.
      During morphogenesis of the craniofacial structures, 5-HT stimulates dental
      development and may aid in cusp formation. All of the most commonly prescribed
      antidepressant drugs inhibit serotonin uptake, yet they do not appear to cause
      major craniofacial malformations in vivo. Given the wide spectrum of effects that
      5-HT has during development, it is difficult to understand why these anti
      depressants are not major teratogens. Redundancy within the system may allow
      receptor and uptake pathways to function normally even with lower than normal
      levels of circulating serotonin. Serotonin-binding proteins, that are expressed
      in most craniofacial regions at critical times during craniofacial development,
      may have a buffering capacity that maintains adequate 5-HT tissue concentrations
      over a wide range of 5-HT serum concentrations. Dental development appears to be
      particularly sensitive to even small fluctuations in concentrations of 5-HT.
      Therefore, it may be that children of patients who have received selective
      serotonergic re-uptake inhibitors (such as Prozac and Zoloft) or the less
      selective tricyclic anti-depressant drugs (such as Elavil) would be at a higher
      risk for developmental dental defects such as anodontia and hypodontia. In this
      review, the evidence supporting a role for 5-HT during mammalian craniofacial
      development is discussed. A series of models is proposed that may explain how the
      craniofacial effects of 5-HT are mediated.

PMID- 12002818
TI  - PAF, a putative mediator of oral inflammation.
AB  - PAF, or platelet-activating factor, is a family of structurally related
      phospholipids (1-O-alkyl/acyl/alkenyl-2-acetyl-sn-glycero-3-phosphocholine) which
      possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids
      are synthesized by a diverse array of cells, including neutrophilic
      polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages,
      vascular endothelial cells, and lymphocytes. PAF targets these and other cells
      via specific, G-protein-coupled receptors to initiate intracrine, autocrine,
      paracrine, and juxtacrine cell activation. Of importance, these unique acetylated
      phospholipids are frequently synthesized in concert with pro-inflammatory lipid
      mediators derived from arachidonic acid. Since PAF synergizes with these and
      other mediators to amplify the inflammatory response, it seems likely that PAF
      plays an integral, perhaps pivotal, role in acute and chronic inflammatory
      processes. PAF is present in the mixed saliva of dentate, but not edentulous,
      human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid
      and tissues are significantly increased during oral inflammatory conditions such
      as periodontitis and mucositis. Interestingly, the levels of salivary PAF
      correlate with the extent/severity of these oral diseases. These observations
      suggest that PAF may participate in pathophysiologic events during the course of
      oral inflammation. The availability of specific PAF receptor antagonists and
      human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly
      destroys PAF, should provide clinical tools for the investigation of the role of
      PAF in these and other inflammatory disorders; and perhaps, ultimately, some of
      these reagents may prove to be therapeutically useful in the treatment and
      management of these conditions.

PMID- 12002819
TI  - Human papillomavirus infections in children: the potential role of maternal
      transmission.
AB  - To date, more than 100 types of human papillomavirus (HPV) have been identified.
      In the past 20 years, there has been an increasing interest in HPVs because of
      their potential role in the pathogenesis of malignant tumors. HPV infections are
      known to affect predominantly adult, sexually active age groups, whereas skin
      warts, at various anatomic sites, are usually associated with younger
      individuals. The modes of viral transmission in children remain controversial,
      including perinatal transmission, auto- and hetero-inoculation, sexual abuse,
      and, possibly, indirect transmission via fomites. Recent studies on perinatal
      infection with HPV have been inconclusive. It is still unclear how frequently
      perinatal infection progresses to clinical lesions, whether genital, laryngeal,
      or oral. Conflicting reports have been published on the prevalence of HPV
      infections in children. The current consensus is, however, that newborn babies
      can be exposed to cervical HPV infection of the mother. The detection rate of HPV
      DNA in oral swabs of newborn babies varies from 4% to 87%. The concordance of HPV
      types detected in newborn babies and their mothers is in the range of 57% to 69%,
      indicating that the infants might acquire the HPV infection post-natally from a
      variety of sources. HPV antibodies have been detected in 10% to 57% of the
      children, and there is usually no correlation between seropositivity and the
      detection of HPV DNA in either the oral or the genital mucosa. There is also
      evidence that transmission in utero or post-natal acquisition is possible. The
      mode of in utero transmission remains unknown, but theoretically the virus could
      be acquired hematogenously, by semen at fertilization, or as an ascending
      infection in the mother. The understanding of viral transmission routes is
      important, particularly because several vaccination programs are being planned
      worldwide. The serologic response to HPV detected in different populations of
      young women or women at risk of cervical cancer might be due to genital
      infections, but the possibility that HPV infection has been acquired earlier in
      life through the oral mucosa or respiratory tract cannot be ruled out.

PMID- 12002820
TI  - Is it time to change state and regional dental licensure board exams in response
      to evidence from caries research?
AB  - State and regional board exams represent the final gateway to dental licensure.
      One would expect that the requirements for licensure would reflect procedures
      that are beneficial to each patient's oral health and that are consistent with
      the teachings of most dental schools. We conducted an Internet survey to
      determine whether Class 2 tooth preparations based on caries lesions whose
      radiolucencies were confined to enamel were allowed for state and regional exams.
      Information obtained for 46 of the 50 states revealed that 33 of the states (72%)
      allowed teeth with either an E1 or E2 lesion to be restored. Seventeen of these
      states allowed teeth with an E1 lesion to be restored. Only 12 of the 46 states
      (26%) covered by these boards did not allow teeth with E1 or E2 lesions to be
      surgically treated. In contrast, a recent report indicates that only 30% of
      dental schools permit teeth with enamel lesions to be restored to satisfy
      clinical requirements and competencies.

PMID- 12002821
TI  - Proteolytic events of wound-healing--coordinated interactions among matrix
      metalloproteinases (MMPs), integrins, and extracellular matrix molecules.
AB  - During wound-healing, cells are required to migrate rapidly into the wound site
      via a proteolytically generated pathway in the provisional matrix, to produce new
      extracellular matrix, and, subsequently, to remodel the newly formed tissue
      matrix during the maturation phase. Two classes of molecules cooperate closely to
      achieve this goal, namely, the matrix adhesion and signaling receptors, the
      integrins, and matrix-degrading and -processing enzymes, the matrix
      metalloproteinases (MMPs). There is now substantial experimental evidence that
      blocking key molecules of either group will prevent or seriously delay wound
      healing. It has been known for some time now that cell adhesion by means of the
      integrins regulates the expression of MMPs. In addition, certain MMPs can bind to
      integrins or other receptors on the cell surface involved in enzyme activation,
      thereby providing a mechanism for localized matrix degradation. By
      proteolytically modifying the existing matrix molecules, the MMPs can then induce
      changes in cell behavior and function from a state of rest to migration. During
      wound repair, the expression of integrins and MMPs is simultaneously up
      regulated. This review will focus on those aspects of the extensive knowledge of
      fibroblast and keratinocyte MMPs and integrins in biological processes that
      relate to wound-healing.

PMID- 12002822
TI  - Role of Treponema denticola in periodontal diseases.
AB  - Among periodontal anaerobic pathogens, the oral spirochetes, and especially
      Treponema denticola, have been associated with periodontal diseases such as early
      onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis.
      Basic research as well as clinical evidence suggest that the prevalence of T
      denticola, together with other proteolytic gram-negative bacteria in high numbers
      in periodontal pockets, may play an important role in the progression of
      periodontal disease. The accumulation of these bacteria and their products in the
      pocket may render the surface lining periodontal cells highly susceptible to
      lysis and damage. T. denticola has been shown to adhere to fibroblasts and
      epithelial cells, as well as to extracellular matrix components present in
      periodontal tissues, and to produce several deleterious factors that may
      contribute to the virulence of the bacteria. These bacterial components include
      outer-sheath-associated peptidases, chymotrypsin-like and trypsin-like
      proteinases, hemolytic and hemagglutinating activities, adhesins that bind to
      matrix proteins and cells, and an outer-sheath protein with pore-forming
      properties. The effects of T. denticola whole cells and their products on a
      variety of host mucosal and immunological cells has been studied extensively
      (Fig. 1). The clinical data regarding the presence of T. denticola in periodontal
      health and disease, together with the basic research results involving the role
      of T. denticola factors and products in relation to periodontal diseases, are
      reviewed and discussed in this article.

PMID- 12002823
TI  - Effect of mechanical loading on periodontal cells.
AB  - Mechanical loading is an important regulatory factor in alveolar bone
      homeostasis, and plays an essential role in maintaining the structure and mass of
      the alveolar processes throughout lifetime. A better understanding of the
      cellular and molecular responses of periodontal cells is a prerequisite for
      further improvements of therapeutic approaches in orthodontics, periodontal and
      alveolar bone repair and regeneration, implantology, and post-surgical wound
      healing. The purpose of this review is to provide an insight into some cell
      culture and animal models used for studying the effects of mechanical loading on
      periodontal cells, and into the recent developments and utilization of new in
      vivo animal models. There has been an increased awareness about the need for
      improvement and development of in vivo models to supplement the widely used cell
      culture models, and for biological validation of in vitro results, especially in
      the light of evidence that developmental models may not always reflect bone
      homeostasis in an adult organism. Due to the limitations of in vivo models,
      previous studies on mechanical regulation of alveolar bone osteoblasts and
      cementoblasts mostly focused on proliferative responses, rather than on the
      stimulation of cell differentiation. To address this problem, we have recently
      characterized and implemented a mouse osteoinductive tooth movement model for
      studying mechanically induced regulation of osteoblast- and cementoblast
      associated genes. In this model, a defined and reproducible mechanical osteogenic
      loading is applied during a time course of up to two weeks. Regulation of gene
      expression in either wild-type or transgenic animals is assessed by a relative
      quantitative measurement of the level of target mRNAs directly within the
      subpopulations of periodontal cells. To date, results demonstrate a defined
      temporal pattern of cell-specific gene regulation in periodontal osteoblasts
      mechanically stimulated to differentiate and deposit bone matrix. The responses
      of osteoblast-associated genes to mechanical loading were 10- to 20-fold greater
      than the increase in the numbers of these cells, indicating that the induction of
      differentiation and an increase of cell function are the primary responses to
      osteogenic loading. The progression of the osteoblast phenotype in the intact
      mouse periodontium was several-fold faster compared with that in cultured cells,
      suggesting that the mechanical signal may be targeting osteoblast precursors in
      the state of readiness to respond to an environmental challenge, without the
      initial proliferative response. An early response of alkaline phosphatase and
      bone sialoprotein genes was detected after 24 hrs of treatment, followed by a
      concomitant stimulation of osteocalcin and collagen I between 24 and 48 hrs, and
      deposition of osteoid after 72 hrs. Although cementoblasts constitutively express
      biochemical markers similar to those of osteoblasts, distinct responses of
      osteocalcin, collagen I, and bone sialoprotein genes to mechanical loading were
      observed in the two cell phenotypes. This finding indicates that differential
      genetic responses to mechanical loading provide functional markers for
      distinction of the cementoblast and osteoblast phenotypes.

PMID- 12002824
TI  - Induction and regulation of crown dentinogenesis: embryonic events as a template
      for dental tissue repair?
AB  - Close regulation of odontoblast differentiation and subsequent secretory activity
      is critical for dentinogenesis during both embryogenesis and tissue repair. Some
      dental papilla cells achieve commitment and specific competence, allowing them to
      respond to epithelially derived inductive signals during the process of
      odontoblast differentiation. Temporo-spatial regulation of odontoblast
      differentiation is dependent on matrix-mediated interactions involving the
      basement membrane (BM). Experimental studies have highlighted the possible roles
      of growth factors in these processes. Regulation of functional activity of
      odontoblasts allows for both ordered secretion of the primary dentin matrix and
      maintenance of vitality and down-regulation of secretory activity throughout
      secondary dentinogenesis. After injury to the mature tooth, the fate of the
      odontoblast can vary according to the intensity of the injury. Milder injury can
      result in up-regulation of functional activity leading to focal secretion of a
      reactionary dentin matrix, while greater injury can lead to odontoblast cell
      death. Induction of differentiation of a new generation of odontoblast-like cells
      can then lead to reparative dentinogenesis. Many similarities exist between
      development and repair, including matrix-mediation of the cellular processes and
      the apparent involvement of growth factors as signaling molecules despite the
      absence of epithelium during repair. While some of the molecular mediators appear
      to be common to these processes, the close regulation of primary dentinogenesis
      may be less ordered during tertiary dentinogenic responses.

PMID- 12002825
TI  - Temporomandibular joint involvement in rheumatoid arthritis: a radiological and
      clinical study.
AB  - Temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) is not
      uncommon. In this study a questionnaire, clinical assessment, and high resolution
      computerized tomography (HRCT) were used in 15 patients with rheumatoid arthritis
      to evaluate the diagnostic criteria of TMJ involvement. Symptoms due to TMJ
      involvement were present in 33.3% of the patients. Frequency of involvement was
      40.0% on clinical assessment but 86.6% with HRCT assessment. The most common HRCT
      findings were decreases in the joint space (33.3%), mandibular subchondral cysts
      (23.3%), temporal subchondral cysts (23.3%), degeneration (23.3%), shape (13.3%)
      and height (13.3%) anomalies of the mandibular condyle, condylar head resorption
      (13.3%), erosion of the mandibular condyle (13.3%), and demineralization (13.3%).
      All patients with positive clinical findings also had positive HRCT findings. In
      seven (46.7%) of the patients, there were no symptoms or clinical findings
      implying TMJ involvement; however, they had positive results on HRCT evaluation.
      The HRCT findings may be the initial sign of TMJ involvement in patients with
      rheumatoid arthritis. In conclusion, it is suggested that RA patients with the
      suspicion of TMJ involvement should undergo HRCT evaluation, because HRCT
      findings may precede the clinical findings.

PMID- 12002826
TI  - Immunohistochemical localization and distribution of proliferating cell nuclear
      antigen in the rabbit mandibular condyle following experimental induction of
      anterior disk displacement.
AB  - The purpose of the present study was to identify proliferating cells in control
      versus experimental condyles two weeks following experimental induction of
      anterior disk displacement (ADD) in the rabbit craniomandibular joint (CMJ). The
      right joint of 15 rabbits was exposed surgically and all diskal attachments were
      severed except for the posterior attachment. The disk was then repositioned
      anteriorly and sutured to the zygomatic arch. The left joint served as a sham
      operated control. Ten additional joints were used as nonoperated controls.
      Mandibular condyles were excised two weeks following surgery and processed for
      proliferating cell nuclear antigen (PCNA) immunostaining. In control and sham
      operated condyles, PCNA was localized in the nuclei of chondroblasts of the
      reserve cell layer, chondrocytes of the upper hypertrophic layer and bone marrow
      cells of the subchondral bone. In contrast to control joints, the PCNA positive
      cells of the experimental joints were located throughout the osteoarthritic
      condylar cartilage. In addition, the percentage of PCNA positive cells of the
      osteoarthritic condylar cartilage was statistically significantly higher when
      compared to the control group, p < 0.05. It was concluded that surgical induction
      of ADD in the rabbit CMJ leads to an increase in mitosis of chondrocytes, which
      lead to cell proliferation and subsequent hyperplasia of the condylar cartilage.

PMID- 12002827
TI  - Microscopic analysis of the temporomandibular joint in rabbits (Oryctolagus
      cuniculus L.) using an occlusal interference.
AB  - The purpose of this study was to assess the tissue alterations in the
      temporomandibular joint (TMJ) of the New Zealand White rabbit (Oryctolagus
      cuniculus L.), after a unilateral occlusal interference insertion on the animal's
      right side back teeth. A total of 36 animals were used, thirty of which belonged
      to the experimental group and six to the control group. We established three
      experimental periods: 24 hours, three days and seven days. The control group
      animals were divided two by two; each pair followed the same experimental periods
      of the former one. The experimental group animals were submitted to the use of a
      0.3 mm thick metallic cap with a visor. All animals were euthanized, and the TMJs
      were removed. Using a microscope for examination we observed, in all experimental
      periods, the presence of intra-articular hemorrhage in the supra- and infra-disk
      compartments as well as in the retro-disk zone. There were no inflammatory cells
      detected. The thickness of the condylar fibrocartilage presented significant
      alterations among the animals of the three experimental groups. In the left TMJs
      no inflammatory cells were detected. The results suggest that the insertion of a
      unilateral occlusal interference in rabbit back teeth does not cause any
      inflammatory intra-articular process within seven days; however, it does cause
      bilateral intra-articular hemorrhage and a larger compression of the condylar
      fibrocartilage in the joint opposite the side where the interference is placed.
      We also concluded that, in order to do research on the temporomandibular joint
      using animals, it is necessary have an independent (or separate) group of animals
      as controls.

PMID- 12002828
TI  - TMD prevalence in rural and urban Native American populations.
AB  - The purpose of this study was to assess the prevalence of TMD in a consecutive
      sample of 102 subjects from the Native American population living in an urban
      setting and 90 subjects living in a rural setting. The study utilized a clinical
      examination and standardized questionnaires. The sample age ranged from five to
      84 years of age. The subjects were asked to estimate pain frequency, severity and
      daily pattern of jaw pain, difficulty in opening, joint clicking, and sleeping
      problems. Examination was performed on joint, masticatory, and cervical muscles,
      as well as occlusion. Data was collected and statistically analyzed.
      Statistically significant differences were found; however, the only statistically
      significant difference that might have clinical significance was more facial pain
      in the urban population.

PMID- 12002829
TI  - Improvement in jaw motion following treatment of unilateral crossbite in a child
      with primary dentition: a case report.
AB  - This case report examines jaw motion during both habitual opening-closing and gum
      chewing in a young (3 years, 10 months) patient with unilateral crossbite at the
      primary dentition stage. Jaw motion was measured three times: 1. before
      treatment; 2. after active treatment; and 3. after retention. The abnormal
      habitual open-close pathway seen prior to treatment was improved after retention.
      Prior to treatment, movement of the affected-side condyle preceded movement of
      the non-affected-side condyle during opening. After retention, the movement of
      the condyles was better coordinated. The chopping type chewing pattern, with less
      lateral movement, before treatment changed to a more grinding type pattern on the
      affected side after activation. This study suggests that the prescribed treatment
      effectively improved both the patient's morphology and function. However, neither
      the open-close pathways nor the chewing patterns were completely normal after
      retention. The results in this case suggest that early treatment of functional
      unilateral crossbite can be effective.

PMID- 12002830
TI  - Sympathetic activity-mediated neuropathic facial pain following simple tooth
      extraction: a case report.
AB  - This is a report of a case of sympathetic activity-mediated neuropathic facial
      pain induced by a traumatic trigeminal nerve injury and by varicella zoster virus
      infection, following a simple tooth extraction. The patient had undergone
      extraction of the right lower third molar at a local dental clinic, and soon
      after the tooth extraction, she became aware of spontaneous pain in the right
      ear, right temporal region, and in the tooth socket. At our initial examination
      30 days after the tooth extraction, the healing of the tooth socket was normal;
      however, the patient had a tingling and burning sensation (dysesthesia) and
      spontaneous pain of the right lower lip and the right temporal region, both of
      which were exacerbated by non-noxious stimuli (allodynia). The patient also
      showed paralysis of the marginal mandibular branch of the facial nerve, taste
      dysfunction, and increased varicella zoster serum titers. A diagnostic stellate
      ganglion block (SGB) 45 days after the tooth extraction using one percent
      lidocaine markedly alleviated the dysesthesia and allodynia. These symptoms are
      characteristic of neuropathic pain with sympathetic interaction. The patient was
      successfully treated with SGB and a tricyclic antidepressant.

PMID- 12002831
TI  - Productive, yet interesting staff meetings for pain practices.

PMID- 12002833
TI  - Dr. Roy K. King responds to Dr. Terrance Spahl's guest editorial in the January
      2002 issue of CRANIO. Generalizations and antagonistic remarks regarding the
      orthodontic profession.

PMID- 12002832
TI  - Dr. Melis comments on Miralles, et al.'s article in the January 2002 issue of
      CRANIO. The relationship between occlusion and the cranio-cervical complex.

PMID- 12002834
TI  - Medical and physical therapy of temporomandibular joint disk displacement without
      reduction.
AB  - The objective of this study was to determine the influence of medical and
      physical therapy on long-term treatment outcome in 72 patients with anterior disk
      displacement without reduction. Patients were treated solely with occlusal
      splints (group I), with splints and supplementary medical therapy (group II),
      with splints and physical therapy (group III) or with splints, medical, and
      physical therapy (group IV). After therapy, the maintenance of improvement was
      objectively and subjectively assessed with an extensive clinical examination and
      a postal questionnaire. The percentage of pain free patients after therapy was
      76% in group I, 88% in group II, 43% in group III, and 65% in group IV. There was
      a statistically significant higher increase of maximum jaw opening after therapy
      in group II than in the control groups (p<0.05). The improvement in mouth opening
      came to 9.7 mm in group I, 14.5 mm in group II, 7.3 mm in group III, and 11.2 mm
      in group IV. Medical therapy seems to have a positive influence on the treatment
      outcome of patients with anterior disk displacement without reduction.

PMID- 12002835
TI  - Relationship between the number of occlusal contacts and masticatory muscle
      activity in healthy young adults.
AB  - The electromyographic (EMG) potentials of left and right masseter and temporalis
      anterior muscles were recorded in 23 healthy young adults during: 1. a 3-second
      maximum voluntary clench (MVC) on cotton rolls positioned on the posterior teeth
      (standardized recording); and 2. a 3-second MVC in intercuspal position. EMG
      potentials recorded in intercuspal position were standardized as a percentage of
      the mean potentials of the standardized recording, and the EMG muscle activity
      was calculated. The number of occlusal contacts in intercuspal position was
      assessed by using eight microm thick shim stocks. Two groups of subjects with
      either 1. Less than ten occlusal contacts (11 subjects with "few contacts"); or
      2. At least ten occlusal contacts (12 subjects with "many contacts") were
      selected. The MVC muscle activity in the "few contacts" group was significantly
      lower than that recorded in the "many contacts" group (p<0.005). In conclusion,
      the number of occlusal contacts and masticatory muscular function are
      significantly related, at least in young adults with a sound stomatognathic
      apparatus.

PMID- 12002836
TI  - Relationship between occlusion and EMG activity of the masseter muscles during
      clenching at maximal intercuspal position: a comparative study between
      prognathics and controls.
AB  - In the prognathic (P) patient group clenching at maximal intercuspal position
      (MIP), we found that the Ar-Go-Me angle is greater than in the control group (C =
      120.9 degrees +/- 7 degrees vs. P = 134.4 degrees +/- 5.2 degrees): the same as
      the masseter fibers angle (alpha). The average EMG voltage class was similar in
      both groups (C = 1488.5 +/- 303.4 microvolt vs. P = 1317.6 +/- 293.4 microvolt).
      The mean total number of contact points in tooth arches was greater in the
      control group than in the patient group (C = 5.77 +/- 0.43 vs. P = 3.07 +/-
      0.29), and there was a greater number of contact points between both premolar and
      molar areas. Both the control group and the patient group showed balanced
      occlusion in the premolar and molar areas. Therefore the finding of a similar
      mean EMG value between the control group and the patients emphasizes the
      importance of balanced contact points in the posterior areas.

PMID- 12002837
TI  - Acoustics of friction.
AB  - This article presents an overview of the acoustics of friction by covering
      friction sounds, friction-induced vibrations and waves in solids, and
      descriptions of other frictional phenomena related to acoustics. Friction,
      resulting from the sliding contact of solids, often gives rise to diverse forms
      of waves and oscillations within solids which frequently lead to radiation of
      sound to the surrounding media. Among the many everyday examples of friction
      sounds, violin music and brake noise in automobiles represent the two extremes in
      terms of the sounds they produce and the mechanisms by which they are generated.
      Of the multiple examples of friction sounds in nature, insect sounds are
      prominent. Friction also provides a means by which energy dissipation takes place
      at the interface of solids. Friction damping that develops between surfaces, such
      as joints and connections, in some cases requires only microscopic motion to
      dissipate energy. Modeling of friction-induced vibrations and friction damping in
      mechanical systems requires an accurate description of friction for which only
      approximations exist. While many of the components that contribute to friction
      can be modeled, computational requirements become prohibitive for their
      contemporaneous calculation. Furthermore, quantification of friction at the
      atomic scale still remains elusive. At the atomic scale, friction becomes a
      mechanism that converts the kinetic energy associated with the relative motion of
      surfaces to thermal energy. However, the description of the conversion to thermal
      energy represented by a disordered state of oscillations of atoms in a solid is
      still not well understood. At the macroscopic level, friction interacts with the
      vibrations and waves that it causes. Such interaction sets up a feedback between
      the friction force and waves at the surfaces, thereby making friction and surface
      motion interdependent. Such interdependence forms the basis for friction-induced
      motion as in the case of ultrasonic motors and other examples. Last, when
      considered phenomenologically, friction and boundary layer turbulence exhibit
      analogous properties and, when compared, each may provide clues to a better
      understanding of the other.

PMID- 12002839
TI  - Comment on "Corrections to Foldy's effective medium theory for propagation in
      bubble clouds and other collections of very small scatterers".

PMID- 12002838
TI  - Incorporating linear viscoelasticity into acoustic scattering theory.

PMID- 12002840
TI  - Geoacoustic inversion for fine-grained sediments.
AB  - Fine-grained water saturated sediments like silty clays have the curious property
      that the speed of sound through its bulk medium is lower than that of the
      interstitial pore fluid. When a fine-grained sediment is at the water-sediment
      interface, classical theory predicts that there is an angle at which the
      reflection coefficient is zero, and there is total transmission of sound into the
      seabed. This angle is called the angle of intromission and has been directly
      observed at the seafloor only rarely. Data from a new measurement technique show
      this phenomenon with remarkable clarity. The presence of the angle of
      intromission creates an opportunity for a direct (i.e., without search) inversion
      for the sediment sound speed and density. Though acoustic techniques generally do
      not estimate sediment density very precisely, this technique is quite sensitive
      to density. Geoacoustic inversion results from reflection measurements in the
      Straits of Sicily compare very favorably with independent "ground truth" data
      indicating that the method is robust.

PMID- 12002841
TI  - Application of an acoustic backscatter technique for characterizing the roughness
      of porous soil.
AB  - An acoustic backscatter technique proposed by Oelze et al. [J. Acoust. Soc. Am.
      109, 1826-1832 (2001)] was used to characterize the roughness of porous soil
      surfaces. Roughness estimation errors are minimized when the effective flow
      resistivity of the porous soil is high, e.g., above 300,000 mks Rayls/m. Four
      soil plots were constructed by roughening soil with farming implements. Three
      plots were sealed using Saran powder dissolved in methyl ethyl ketone (MEK) and
      then covered to prevent further weathering. A fourth plot was left in the open
      and exposed to rainfall, which also acted to seal the surface and further change
      the roughness. In sealing the surface the effective flow resistivity of the
      surface was increased above 300,000 mks Rayls/m, which is typical for weathered
      agricultural surfaces. The roughness power spectra of the soil surfaces were
      measured by acoustic backscatter and alternatively by a laser profiler.
      Regression analysis was used to approximate each roughness power spectrum versus
      roughness wave number with a best-fit line. The best-fit line was used to
      calculate the rms height and the correlation length of the rough surface by
      integrating the approximate roughness power spectrum over a range of roughness
      wave number values. The range of roughness wave number values defines the
      roughness length scales used in the statistical calculations. High-roughness wave
      numbers correspond to smaller length scales of roughness and low-roughness wave
      numbers correspond to larger length scales of roughness. Over certain ranges of
      roughness wave number values the statistics from the acoustic backscatter and
      laser profiler measurements is in good agreement. However, as the low-cutoff
      roughness wave number is decreased and the high-cutoff roughness wave number is
      increased, agreement between the laser and acoustic techniques diminishes.

PMID- 12002842
TI  - Theoretical and experimental examination of near-field acoustic levitation.
AB  - A planar object can be levitated stably close to a piston sound source by making
      use of acoustic radiation pressure. This phenomenon is called near-field acoustic
      levitation [Y. Hashimoto et al., J. Acoust. Soc. Am. 100, 2057-2061 (1996)]. In
      the present article, the levitation distance is predicted theoretically by
      numerically solving basic equations in a compressible viscous fluid subject to
      the appropriate initial and boundary conditions. Additionally, experiments are
      carried out using a 19.5-kHz piston source with a 40-mm aperture and various
      aluminum disks of different sizes. The measured levitation distance agrees well
      with the theory, which is different from a conventional theory, and the
      levitation distance is not inversely proportional to the square root of the
      surface density of the levitated disk in a strict sense.

PMID- 12002843
TI  - An integrated wave-effects model for an underwater explosion bubble.
AB  - A model for a moderately deep underwater explosion bubble is developed that
      integrates the shock wave and oscillation phases of the motion. A hyperacoustic
      relationship is formulated that relates bubble volume acceleration to far-field
      pressure profile during the shock-wave phase, thereby providing initial
      conditions for the subsequent oscillation phase. For the latter, equations for
      bubble-surface response are derived that include wave effects in both the
      external liquid and the internal gas. The equations are then specialized to the
      case of a spherical bubble, and bubble-surface displacement histories are
      calculated for dilational and translational motion. Agreement between these
      histories and experimental data is found to be substantially better than that
      produced by previous models.

PMID- 12002844
TI  - Viscous effects on the interaction force between two small gas bubbles in a weak
      acoustic field.
AB  - The relative motion of two gas bubbles in an acoustic field is investigated by
      calculating the time-averaged interaction force known as the secondary Bjerknes
      force. The surrounding medium is assumed to be an incompressible viscous liquid
      and the separation distance between the bubbles much larger than their radii. A
      refined formula for the interaction force is derived, which allows for
      translational oscillations of the bubbles, the vorticity of the linear scattered
      field, and acoustic streaming. The boundary condition of slippage on the gas
      liquid interface is assumed. It is shown that viscous effects can cause small
      bubbles, driven well below resonance, to repel each other within a relatively
      wide parameter range. This result discloses a significant boundedness of the
      classical Bjerknes theory according to which bubbles of this sort are capable of
      mutual attraction alone.

PMID- 12002845
TI  - Efficient calculation of two-dimensional periodic and waveguide acoustic Green's
      functions.
AB  - New representations and efficient calculation methods are derived for the problem
      of propagation from an infinite regularly spaced array of coherent line sources
      above a homogeneous impedance plane, and for the Green's function for sound
      propagation in the canyon formed by two infinitely high, parallel rigid or sound
      soft walls and an impedance ground surface. The infinite sum of source
      contributions is replaced by a finite sum and the remainder is expressed as a
      Laplace-type integral. A pole subtraction technique is used to remove poles in
      the integrand which lie near the path of integration, obtaining a smooth
      integrand, more suitable for numerical integration, and a specific numerical
      integration method is proposed. Numerical experiments show highly accurate
      results across the frequency spectrum for a range of ground surface types. It is
      expected that the methods proposed will prove useful in boundary element modeling
      of noise propagation in canyon streets and in ducts, and for problems of
      scattering by periodic surfaces.

PMID- 12002846
TI  - Coupled-mode solutions in generalized ocean environments.
AB  - This paper presents the application of the differential equation approach to
      solving the second-order coupled-mode equations in inhomogeneous ocean
      environments. The model incorporates sound velocity profile points to construct
      depth-dependent, piecewise linear, ocean and bottom environments along a range
      grid. Modal solutions are evaluated in terms of Airy functions. The formalism to
      evaluate analytically the mode-coupling coefficients is presented. Comparisons to
      conventional expressions of the coefficients are made. The integro-differential
      form of the coupled equations is solved using an approach developed in nuclear
      theory that incorporates the Lanczos method [Knobles, J. Acoust. Soc. Am. 96,
      1741-1747 (1994)]. Demonstration of the practicality of this approach is made by
      applying the results in actual calculations with realistic ocean environments.
      The formalism to evaluate analytically the mode-coupling coefficients is
      presented. Several benchmark examples were examined in order to validate the
      model and are discussed, including propagation over a hill, benchmark wedge
      problems, and a range-varying sound speed profile benchmark. The importance of
      this model is also demonstrated by the physical insight gained in having a
      coupled-mode approach to solving range-dependent problems.

PMID- 12002847
TI  - Comparing Kirchhoff-approximation and boundary-element models for computing
      gadoid target strengths.
AB  - To establish the validity of the boundary-element method (BEM) for modeling
      scattering by swimbladder-bearing fish, the BEM is exercised in several ways. In
      a computation of backscattering by a 50-mm-diam spherical void in sea water at
      the four frequencies 38.1, 49.6, 68.4, and 120.4 kHz, agreement with the
      analytical solution is excellent. In computations of target strength as a
      function of tilt angle for each of 15 surface-adapted gadoids for which the
      swimbladders were earlier mapped, BEM results are in close agreement with
      Kirchhoff-approximation-model results at each of the same four frequencies. When
      averaged with respect to various tilt angle distributions and combined by
      regression analysis, the two models yield similar results. Comparisons with
      corresponding values derived from measured target strength functions of the same
      15 gadoid specimens are fair, especially for the tilt angle distribution with the
      greatest standard deviation, namely 16 degrees.

PMID- 12002848
TI  - Coherence of acoustic modes propagating through shallow water internal waves.
AB  - The 1995 Shallow Water Acoustics in a Random Medium (SWARM) experiment [Apel et
      al., IEEE J. Ocean. Eng. 22, 445-464 (1997)] was conducted off the New Jersey
      coast. The experiment featured two well-populated vertical receiving arrays,
      which permitted the measured acoustic field to be decomposed into its normal
      modes. The decomposition was repeated for successive transmissions allowing the
      amplitude of each mode to be tracked. The modal amplitudes were observed to
      decorrelate with time scales on the order of 100 s [Headrick et al., J. Acoust.
      Soc. Am. 107(1), 201-220 (2000)]. In the present work, a theoretical model is
      proposed to explain the observed decorrelation. Packets of intense internal waves
      are modeled as coherent structures moving along the acoustic propagation path
      without changing shape. The packets cause mode coupling and their motion results
      in a changing acoustic interference pattern. The model is consistent with the
      rapid decorrelation observed in SWARM. The model also predicts the observed
      partial recorrelation of the field at longer time scales. The model is first
      tested in simple continuous-wave simulations using canonical representations for
      the internal waves. More detailed time-domain simulations are presented mimicking
      the situation in SWARM. Modeling results are compared to experimental data.

PMID- 12002849
TI  - Determination of elastic moduli of rock samples using resonant ultrasound
      spectroscopy.
AB  - Resonant ultrasound spectroscopy (RUS) is a method whereby the elastic tensor of
      a sample is extracted from a set of measured resonance frequencies. RUS has been
      used successfully to determine the elastic properties of single crystals and
      homogeneous samples. In this paper, we study the application of RUS to
      macroscopic samples of mesoscopically inhomogeneous materials, specifically rock.
      Particular attention is paid to five issues: the scale of mesoscopic
      inhomogeneity, imprecision in the figure of the sample, the effects of low Q,
      optimizing the data sets to extract the elastic tensor reliably, and sensitivity
      to anisotropy. Using modeling and empirical testing, we find that many of the
      difficulties associated with using RUS on mesoscopically inhomogeneous materials
      can be mitigated through the judicious choice of sample size and sample aspect
      ratio.

PMID- 12002850
TI  - Saturation of thermoacoustic mixture separation.
AB  - The theory for thermoacoustic mixture separation is extended to include the
      effects of a nonzero concentration gradient. New data are presented, which are in
      excellent agreement with this theory. The maximum concentration gradient which
      may be achieved in a binary mixture of gases through this separation process is
      intrinsically limited by the fractional pressure amplitude, by the tidal
      displacement, and by the size of the thermal diffusion ratio. Ordinary diffusion
      further detracts from the attainable final concentration gradient and can become
      the dominant remixing process as the cross section of the duct is increased.
      Rayleigh streaming also works against thermoacoustic separation, and an estimate
      of the molar flux from streaming is given.

PMID- 12002851
TI  - Hybrid laser/broadband EMAT ultrasonic system for characterizing cracks in
      metals.
AB  - Detection and characterization of defects in metal parts in industrial and
      commercial settings has typically been carried out by nondestructive ultrasonic
      inspection systems. Correct measurement of crack size is critical for lifetime
      prediction inspections. Normally, measurements are made based on far-field
      ultrasonic diffraction models and time-of-flight reflection signals making
      accurate measurements for parts less than approximately 25 mm in thickness
      impossible. In this work a hybrid noncontacting laser generation/broadband
      electromagnetic acoustic transducer (EMAT) detection system is used to
      characterize ideal cracks in aluminum in which the far-field condition for
      ultrasonic diffraction cannot be met. Time domain signals show that diffracted
      energy is measured in the geometrical shadow zone of the crack. Fourier transform
      methods are used to show that the frequency content of the diffracted signals is
      different than those from the waves that do not interact with the crack. Crack
      size measurements are made by using the frequency content of the ultrasonic
      signal rather than time-of-flight information.

PMID- 12002852
TI  - Performance of a low-frequency, multi-resonant broadband Tonpilz transducer.
AB  - The underwater performance of a high-power multi-resonant Tonpilz transducer with
      a nearly flat frequency response and a power handling capability of 2 kW (peak)
      is reported here. A maximum transmitting voltage response (TVR) value of 156 dB
      re: 1 microPa/V at 1 m has been achieved at 3 kHz with a specially designed
      matching coil. A maximum receiving sensitivity (RS) of -164 dB re: 1 V/microPa at
      3 kHz has been measured without using a matching coil. The horizontal half-power
      beam width of the transducer at 4 kHz is 101 degrees with a directivity index of
      4 dB. This transmitter can be used for oceanographic applications such as
      subbottom profiling as well as long-range underwater communication.

PMID- 12002853
TI  - Generation of an acoustically bright zone with an illuminated region using
      multiple sources.
AB  - This article addresses the way in which we can generate an "acoustically bright
      zone" in a space. The bright zone is defined as the volume where we can have
      higher acoustic energy than in other space. A method is proposed to generate the
      bright zone by controlling multiple monopole sources. Two kinds of cost functions
      involved with acoustic brightness are defined. One is the ratio of the brightness
      of a zone to the input power, and the other expresses the "contrast" between the
      bright zone and the other space. Through eigenvalue analysis, the optimal volume
      velocity distribution of the monopoles has been obtained.

PMID- 12002854
TI  - Experimental study of vibrational behavior of laminated annular disks.
AB  - The purpose of this paper is to present an experimental study of the vibrational
      behavior of laminated annular disks, and effects of laminations on the vibrations
      of the disks. The vibrations of a series of solid annular disks were calculated
      using the finite-element method in order to provide a basis for comparison with
      experimental data. An extensive range of experiments was performed on both a
      series of solid disks and a series of laminated disks under a range of normal
      clamping pressures. Based on the calculated and experimental results, it was
      found that the vibrational behavior of the laminated disks was dominated by that
      of the individual disk, of which the laminated disks were composed. Laminations
      had great effects on the vibrational behavior of the laminated disks and the
      effects depended upon the mode type, the clamping pressure, and the number of
      disk assembly. Laminations increased damping and reduced the amplitude of
      frequency response function for both the transverse modes and in-plane modes of
      disks. The resonant frequency of transverse modes shifted higher because of the
      effects of laminations. For the in-plane vibrational modes, the effects on the
      resonant frequency could be neglected and the resonant frequency could be
      considered to be a constant.

PMID- 12002855
TI  - Maximum likelihood estimation of structural wave components from noisy data.
AB  - In this paper, a general framework is developed for determining the underlying
      parameters of general signal models through the application of maximum likelihood
      estimation theory for functions whose variables separate. This method extends
      previous work in sinusoidal and exponential estimation to include models with
      other functional bases, such as exponential functions with nonconstant amplitudes
      and Bessel functions. Nonuniform spatial sampling is also possible with this
      technique. The maximum likelihood method is applied to the identification of wave
      components along one-dimensional structural elements. Results are given which
      demonstrate the viability and accuracy of the technique estimating exponential
      and Bessel function model parameters from noisy simulation data.

PMID- 12002856
TI  - Global damping of noise or vibration fields with locally synthesized controllers.
AB  - A locally synthesized controller (LSC) is one that uses a local feedback signal
      in a noise or vibration field (VF) to synthesize the actuation signal. The global
      damping of a VF by available LSCs requires sensor-actuator collocation. This
      study presents a LSC for the global damping of a VF without requiring sensor
      actuator collocation, which is important to noise control applications where a
      sensor may be placed away from an actuator to avoid the near field effects. It is
      proven that the LSC damps the entire VF instead of just a local feedback loop.
      This is different from other LSCs that may control local feedback loops without
      damping the VFs. A decentralized control law is presented here to extend the LSC
      to a decentralized damping system using multiple actuators.

PMID- 12002857
TI  - Analysis of noise barrier overlap gaps.
AB  - Sound propagation through the gap produced by two parallel vertical barriers with
      overlapped ends is formulated for traffic noise sources. The analysis identifies
      both source and receiver regions according to the mechanisms that influence noise
      propagation in the vicinity of an overlap gap. A method to account for the
      contributions from the various source regions for a given receiver location is
      described. The derived method can be implemented using various equations for
      sound propagation. The results of using equations approved by the United States
      Federal Highway Administration for traffic noise propagation are given.
      Uncalibrated predictions are compared with field measurements for up to 30
      receiver positions from each of four overlap gaps. The relative importance of
      contributions from reflected rays to the noise levels at receiver positions is
      given. The analysis confirms the initial hypothesis that a commonly used strategy
      of overlapping barriers by an amount equal to two or three times the overlap
      width is useful for controlling line-of-sight propagation but ignores the
      substantial effect of reflections.

PMID- 12002858
TI  - Relationship between low-frequency aircraft noise and annoyance due to rattle and
      vibration.
AB  - A near-replication of a study of the annoyance of rattle and vibration
      attributable to aircraft noise [Fidell et al., J. Acoust. Soc. Am. 106, 1408-1415
      (1999)] was conducted in the vicinity of Minneapolis-St. Paul International
      Airport (MSP). The findings of the current study were similar to those reported
      earlier with respect to the types of objects cited as sources of rattle in homes,
      frequencies of notice of rattle, and the prevalence of annoyance due to aircraft
      noise-induced rattle. A reliably lower prevalence rate of annoyance (but not of
      complaints) with rattle and vibration was noted among respondents living in homes
      that had been treated to achieve a 5-dB improvement in A-weighted noise reduction
      than among respondents living in untreated homes. This difference is not due to
      any substantive increase in low-frequency noise reduction of acoustically treated
      homes, but may be associated with installation of nonrattling windows. Common
      interpretations of the prevalence of a consequential degree of annoyance
      attributable to low-frequency aircraft noise may be developed from the combined
      results of the present and prior studies.

PMID- 12002859
TI  - Synthesis of a robust broadband duct ANC system using convex programming
      approach.
AB  - A robust active controller using spatially feedforward structure is proposed for
      broadband attenuation of noise in ducts. To meet the requirements of performance
      and robust stability in the presence of plant uncertainties, an H2 cost function
      and an H(infinity) constrain are employed in the synthesis of the controller. The
      design is then converted into a convex programming problem using Q
      parametrization and frequency discretization. An optimal controller that
      satisfies the quadratic cost functions and linear inequality constraints can be
      found by sequential quadratic programming. The optimal controller was implemented
      via a digital signal processor (DSP) and verified by experiments. Experiment
      results showed that the system attained 16.5 dB maximal attenuation and 5.9 dB
      total attenuation in the frequency band 200-600 Hz.

PMID- 12002860
TI  - Experimental evaluation of leaky least-mean-square algorithms for active noise
      reduction in communication headsets.
AB  - An adaptive leaky normalized least-mean-square (NLMS) algorithm has been
      developed to optimize stability and performance of active noise cancellation
      systems. The research addresses LMS filter performance issues related to
      insufficient excitation, nonstationary noise fields, and time-varying signal-to
      noise ratio. The adaptive leaky NLMS algorithm is based on a Lyapunov tuning
      approach in which three candidate algorithms, each of which is a function of the
      instantaneous measured reference input, measurement noise variance, and filter
      length, are shown to provide varying degrees of tradeoff between stability and
      noise reduction performance. Each algorithm is evaluated experimentally for
      reduction of low frequency noise in communication headsets, and stability and
      noise reduction performance are compared with that of traditional NLMS and fixed
      leakage NLMS algorithms. Acoustic measurements are made in a specially designed
      acoustic test cell which is based on the original work of Ryan et al. ["Enclosure
      for low frequency assessment of active noise reducing circumaural headsets and
      hearing protection," Can. Acoust. 21, 19-20 (1993)] and which provides a highly
      controlled and uniform acoustic environment. The stability and performance of the
      active noise reduction system, including a prototype communication headset, are
      investigated for a variety of noise sources ranging from stationary tonal noise
      to highly nonstationary measured F-16 aircraft noise over a 20 dB dynamic range.
      Results demonstrate significant improvements in stability of Lyapunov-tuned LMS
      algorithms over traditional leaky or nonleaky normalized algorithms, while
      providing noise reduction performance equivalent to that of the NLMS algorithm
      for idealized noise fields.

PMID- 12002861
TI  - Wheel/rail noise generation due to nonlinear effects and parametric excitation.
AB  - Two models are developed, one in the time domain and another in the frequency
      domain, to explain when a wheel/rail noise generation model requires the
      inclusion of discrete supports, parametric excitation, and the nonlinear contact
      spring. Numerical simulations indicate the inclusion of discrete supports to
      describe low frequency response, and also at higher frequencies, especially where
      the rail is very smooth or has a corrugation/wavelength corresponding to the
      pinned-pinned frequency. With a corrugation, it may become essential to include
      the nonlinear contact spring, as contact loss occurs at high corrugation
      amplitudes. As nonlinearity causes force generation over a broad frequency range,
      some contributions excite wheel resonances, resulting in high radiation levels,
      that require the inclusion of wheel/rail nonlinear effects and parametric
      excitation for accurate prediction.

PMID- 12002862
TI  - Acoustic and dynamic mechanical properties of a polyurethane rubber.
AB  - Acoustical and dynamic mechanical measurements were carried out on a commercial
      polyurethane rubber, DeSoto PR1547. The sound speed and attenuation were measured
      over the range from 12.5 to 75 kHz and 3.9 to 33.6 degrees C. Shear modulus was
      measured from 10(-4) to 2 Hz and -36 to 34 degrees C. The peak heights of the
      shear loss tangent varied with temperature, demonstrating thermorheological
      complexity. At higher temperatures, time-temperature superpositioning could be
      applied, with the shift factors following the Williams-Landel-Ferry equation.
      From the combined acoustical and mechanical measurements, values for the dynamic
      bulk modulus were determined. Moreover, superposition of the bulk modulus data
      was achieved using the shift factors determined from the dynamic mechanical shear
      measurements. Finally, this work illustrates the capability and the working rules
      of acoustical measurements in a small tank.

PMID- 12002863
TI  - High power ultrasound standard.
AB  - A sensitive radiation force balance for laboratory measurement of ultrasonic
      power is presented. The principle of the system is based on measuring the
      ultrasonic radiation force exerted on a conical float suspended in water.
      Technical details of the implementation of the economically attractive system are
      described. The operation of the system is automated with the aid of the IEEE-488
      bus and a desktop computer. Design aspects that affect measurement uncertainty
      are investigated. A theoretical model for the measurement of ultrasonic power
      with a conical reflector target is discussed. The expanded uncertainty (95%
      confidence level) of the above radiation force conical float system is estimated
      to be between 5% to 10%.

PMID- 12002864
TI  - Sources of DPOAEs revealed by suppression experiments, inverse fast Fourier
      transforms, and SFOAEs in impaired ears.
AB  - DPOAE sources are modeled by intermodulation distortion generated near the f2
      place and a reflection of this distortion near the DP place. In a previous paper,
      inverse fast Fourier transforms (IFFTs) of DPOAE filter functions in normal ears
      were consistent with this model [Konrad-Martin et al., J. Acoust. Soc. Am. 109,
      2862-2879 (2001)]. In the present article, similar measurements were made in ears
      with specific hearing-loss configurations. It was hypothesized that hearing loss
      at f2 or DP frequencies would influence the relative contributions to the DPOAE
      from the corresponding basilar membrane places, and would affect the relative
      magnitudes of SFOAEs at frequencies equal to f2 and fDP. DPOAEs were measured
      with f2 = 4 kHz, f1 varied, and a suppressor near fDP. L2 was 25-55 dB SPL (L1 =
      L2 + 10 dB). SFOAEs were measured at f2 and at 2.7 kHz (the average fDP produced
      by the f1 sweep) for stimulus levels of 20-60 dB SPL. SFOAE results supported
      predictions of the pattern of amplitude differences between SFOAEs at 4 and 2.7
      kHz for sloping losses, but did not support predictions for the rising- and flat
      loss categories. Unsuppressed IFFTs for rising losses typically had one peak.
      IFFTs for flat or sloping losses typically have two or more peaks; later peaks
      were more prominent in ears with sloping losses compared to normal ears. Specific
      predictions were unambiguously supported by the results for only four of ten
      cases, and were generally supported in two additional cases. Therefore, the
      relative contributions of the two DPOAE sources often were abnormal in impaired
      ears, but not always in the predicted manner.

PMID- 12002865
TI  - Pure-tone threshold estimation from extrapolated distortion product otoacoustic
      emission I/O-functions in normal and cochlear hearing loss ears.
AB  - A new method for direct pure-tone threshold estimation from input/output
      functions of distortion product otoacoustic emissions (DPOAEs) in humans is
      presented. Previous methods use statistical models relating DPOAE level to
      hearing threshold including additional parameters e.g., age or slope of DPOAE I/O
      function. Here we derive a DPOAE threshold from extrapolated DPOAE I/O-functions
      directly. Cubic 2 f1-f2 distortion products and pure-tone threshold at f2 were
      measured at 51 frequencies between f2=500 Hz and 8 kHz at up to ten primary tone
      levels between L2=65 and 20 dB SPL in 30 normally hearing and 119 sensorineural
      hearing loss ears. Using an optimized primary tone level setting (L1 = 0.4L2 + 39
      dB) that accounts for the nonlinear interaction of the two primaries at the DPOAE
      generation site at f2, the pressure of the 2 f1-f2 distortion product pDP is a
      linear function of the primary tone level L2. Linear regression yields
      correlation coefficients higher than 0.8 in the majority of the DPOAE I/O
      functions. The linear behavior is sufficiently fulfilled for all frequencies in
      normal and impaired hearing. This suggests that the observed linear functional
      dependency is quite general. Extrapolating towards pDP=0 yields the DPOAE
      threshold for L2. There is a significant correlation between DPOAE threshold and
      pure-tone threshold (r=0.65, p<0.001). Thus, the DPOAEs that reflect the
      functioning of an essential element of peripheral sound processing enable a
      reliable estimation of cochlear hearing threshold up to hearing losses of 50 dBHL
      without any statistical data.

PMID- 12002866
TI  - Rhythmic masking release: contribution of cues for perceptual organization to the
      cross-spectral fusion of concurrent narrow-band noises.
AB  - The contribution of temporal asynchrony, spatial separation, and frequency
      separation to the cross-spectral fusion of temporally contiguous brief narrow
      band noise bursts was studied using the Rhythmic Masking Release paradigm (RMR).
      RMR involves the discrimination of one of two possible rhythms, despite
      perceptual masking of the rhythm by an irregular sequence of sounds identical to
      the rhythmic bursts, interleaved among them. The release of the rhythm from
      masking can be induced by causing the fusion of the irregular interfering sounds
      with concurrent "flanking" sounds situated in different frequency regions. The
      accuracy and the rated clarity of the identified rhythm in a 2-AFC procedure were
      employed to estimate the degree of fusion of the interferring sounds with
      flanking sounds. The results suggest that while synchrony fully fuses short
      duration noise bursts across frequency and across space (i.e., across ears and
      loudspeakers), an asynchrony of 20-40 ms produces no fusion. Intermediate
      asynchronies of 10-20 ms produce partial fusion, where the presence of other cues
      is critical for unambiguous grouping. Though frequency and spatial separation
      reduced fusion, neither of these manipulations was sufficient to abolish it. For
      the parameters varied in this study, stimulus onset asynchrony was the dominant
      cue determining fusion, but there were additive effects of the other cues.
      Temporal synchrony appears to be critical in determining whether brief sounds
      with abrupt onsets and offsets are heard as one event or more than one.

PMID- 12002867
TI  - Assessing auditory distance perception using virtual acoustics.
AB  - In most naturally occurring situations, multiple acoustic properties of the sound
      reaching a listener's ears change as sound source distance changes. Because many
      of these acoustic properties, or cues, can be confounded with variation in the
      acoustic properties of the source and the environment, the perceptual processes
      subserving distance localization likely combine and weight multiple cues in order
      to produce stable estimates of sound source distance. Here, this cue-weighting
      process is examined psychophysically, using a method of virtual acoustics that
      allows precise measurement and control of the acoustic cues thought to be salient
      for distance perception in a representative large-room environment. Though
      listeners' judgments of sound source distance are found to consistently and
      exponentially underestimate true distance, the perceptual weight assigned to two
      primary distance cues (intensity and direct-to-reverberant energy ratio) varies
      substantially as a function of both sound source type (noise and speech) and
      angular position (0 degrees and 90 degrees relative to the median plane). These
      results suggest that the cue-weighting process is flexible, and able to adapt to
      individual distance cues that vary as a result of source properties and
      environmental conditions.

PMID- 12002868
TI  - Glottal flow through a two-mass model: comparison of Navier-Stokes solutions with
      simplified models.
AB  - A new numerical model of the vocal folds is presented based on the well-known two
      mass models of the vocal folds. The two-mass model is coupled to a model of
      glottal airflow based on the incompressible Navier-Stokes equations. Glottal
      waves are produced using different initial glottal gaps and different subglottal
      pressures. Fundamental frequency, glottal peak flow, and closed phase of the
      glottal waves have been compared with values known from the literature. The
      phonation threshold pressure was determined for different initial glottal gaps.
      The phonation threshold pressure obtained using the flow model with Navier-Stokes
      equations corresponds better to values determined in normal phonation than the
      phonation threshold pressure obtained using the flow model based on the Bernoulli
      equation. Using the Navier-Stokes equations, an increase of the subglottal
      pressure causes the fundamental frequency and the glottal peak flow to increase,
      whereas the fundamental frequency in the Bernoulli-based model does not change
      with increasing pressure.

PMID- 12002869
TI  - American and Swedish children's acquisition of vowel duration: effects of vowel
      identity and final stop voicing.
AB  - Vowel durations typically vary according to both intrinsic (segment-specific) and
      extrinsic (contextual) specifications. It can be argued that such variations are
      due to both predisposition and cognitive learning. The present report utilizes
      acoustic phonetic measurements from Swedish and American children aged 24 and 30
      months to investigate the hypothesis that default behaviors may precede language
      specific learning effects. The predicted pattern is the presence of final
      consonant voicing effects in both languages as a default, and subsequent learning
      of intrinsic effects most notably in the Swedish children. The data, from 443
      monosyllabic tokens containing high-front vowels and final stop consonants, are
      analyzed in statistical frameworks at group and individual levels. The results
      confirm that Swedish children show an early tendency to vary vowel durations
      according to final consonant voicing, followed only six months later by a stage
      at which the intrinsic influence of vowel identity grows relatively more robust.
      Measures of vowel formant structure from selected 30-month-old children also
      revealed a tendency for children of this age to focus on particular acoustic
      contrasts. In conclusion, the results indicate that early acquisition of vowel
      specifications involves an interaction between language-specific features and
      articulatory predispositions associated with phonetic context.

PMID- 12002870
TI  - Gender differences in vocal fold contact computed from electroglottographic
      signals: the influence of measurement criteria.
AB  - EGGW is a phonatory parameter that can be derived from electroglottographic (EGG)
      signals and used to infer the relative degree of vocal fold contact. Vocal fold
      models predict that men will exhibit medial bulging of their vocal folds during
      phonation but women will not. These models lead us to expect gender differences
      in the magnitude of EGGW. Nevertheless, significant gender differences in EGGW
      for adults with normal voices have not been documented in previous studies when
      EGGW was computed from criterion lines placed at 25%-40% of the amplitude of the
      uninverted EGG wave form. We hypothesized that EGGW would better reflect gender
      differences in vocal fold adductory patterns if EGGW was computed from portions
      of the wave form that were associated with more vocal fold contact. EGGW was
      measured for seven men and seven women with normal voices. When EGGW was computed
      from segments of the wave form that were associated with relatively greater vocal
      fold contact (i.e., using criterion levels of > or = 55%), findings were
      consistent with the gender-specific adductory patterns that have been proposed
      from vocal fold models. Guidelines for appropriate placement of criterion lines
      when computing EGGW are discussed.

PMID- 12002871
TI  - Toward a model for lexical access based on acoustic landmarks and distinctive
      features.
AB  - This article describes a model in which the acoustic speech signal is processed
      to yield a discrete representation of the speech stream in terms of a sequence of
      segments, each of which is described by a set (or bundle) of binary distinctive
      features. These distinctive features specify the phonemic contrasts that are used
      in the language, such that a change in the value of a feature can potentially
      generate a new word. This model is a part of a more general model that derives a
      word sequence from this feature representation, the words being represented in a
      lexicon by sequences of feature bundles. The processing of the signal proceeds in
      three steps: (1) Detection of peaks, valleys, and discontinuities in particular
      frequency ranges of the signal leads to identification of acoustic landmarks. The
      type of landmark provides evidence for a subset of distinctive features called
      articulator-free features (e.g., [vowel], [consonant], [continuant]). (2)
      Acoustic parameters are derived from the signal near the landmarks to provide
      evidence for the actions of particular articulators, and acoustic cues are
      extracted by sampling selected attributes of these parameters in these regions.
      The selection of cues that are extracted depends on the type of landmark and on
      the environment in which it occurs. (3) The cues obtained in step (2) are
      combined, taking context into account, to provide estimates of "articulator
      bound" features associated with each landmark (e.g., [lips], [high], [nasal]).
      These articulator-bound features, combined with the articulator-free features in
      (1), constitute the sequence of feature bundles that forms the output of the
      model. Examples of cues that are used, and justification for this selection, are
      given, as well as examples of the process of inferring the underlying features
      for a segment when there is variability in the signal due to enhancement gestures
      (recruited by a speaker to make a contrast more salient) or due to overlap of
      gestures from neighboring segments.

PMID- 12002872
TI  - Auditory normalization of French vowels synthesized by an articulatory model
      simulating growth from birth to adulthood.
AB  - The present article aims at exploring the invariant parameters involved in the
      perceptual normalization of French vowels. A set of 490 stimuli, including the
      ten French vowels /i y u e o o E oe (inverted c) a/ produced by an articulatory
      model, simulating seven growth stages and seven fundamental frequency values, has
      been submitted as a perceptual identification test to 43 subjects. The results
      confirm the important effect of the tonality distance between F1 and f0 in
      perceived height. It does not seem, however, that height perception involves a
      binary organization determined by the 3-3.5-Bark critical distance. Regarding
      place of articulation, the tonotopic distance between F1 and F2 appears to be the
      best predictor of the perceived front-back dimension. Nevertheless, the role of
      the difference between F2 and F3 remains important. Roundedness is also examined
      and correlated to the effective second formant, involving spectral integration of
      higher formants within the 3.5-Bark critical distance. The results shed light on
      the issue of perceptual invariance, and can be interpreted as perceptual
      constraints imposed on speech production.

PMID- 12002873
TI  - Quantifying the intelligibility of speech in noise for non-native listeners.
AB  - When listening to languages learned at a later age, speech intelligibility is
      generally lower than when listening to one's native language. The main purpose of
      this study is to quantify speech intelligibility in noise for specific
      populations of non-native listeners, only broadly addressing the underlying
      perceptual and linguistic processing. An easy method is sought to extend these
      quantitative findings to other listener populations. Dutch subjects listening to
      Germans and English speech, ranging from reasonable to excellent proficiency in
      these languages, were found to require a 1-7 dB better speech-to-noise ratio to
      obtain 50% sentence intelligibility than native listeners. Also, the psychometric
      function for sentence recognition in noise was found to be shallower for non
      native than for native listeners (worst-case slope around the 50% point of
      7.5%/dB, compared to 12.6%/dB for native listeners). Differences between native
      and non-native speech intelligibility are largely predicted by linguistic entropy
      estimates as derived from a letter guessing task. Less effective use of context
      effects (especially semantic redundancy) explains the reduced speech
      intelligibility for non-native listeners. While measuring speech intelligibility
      for many different populations of listeners (languages, linguistic experience)
      may be prohibitively time consuming, obtaining predictions of non-native
      intelligibility from linguistic entropy may help to extend the results of this
      study to other listener populations.

PMID- 12002874
TI  - YIN, a fundamental frequency estimator for speech and music.
AB  - An algorithm is presented for the estimation of the fundamental frequency (F0) of
      speech or musical sounds. It is based on the well-known autocorrelation method
      with a number of modifications that combine to prevent errors. The algorithm has
      several desirable features. Error rates are about three times lower than the best
      competing methods, as evaluated over a database of speech recorded together with
      a laryngograph signal. There is no upper limit on the frequency search range, so
      the algorithm is suited for high-pitched voices and music. The algorithm is
      relatively simple and may be implemented efficiently and with low latency, and it
      involves few parameters that must be tuned. It is based on a signal model
      (periodic signal) that may be extended in several ways to handle various forms of
      aperiodicity that occur in particular applications. Finally, interesting
      parallels may be drawn with models of auditory processing.

PMID- 12002875
TI  - Modeling sound transmission through the pulmonary system and chest with
      application to diagnosis of a collapsed lung.
AB  - A theoretical and experimental study was undertaken to examine the feasibility of
      using audible-frequency vibro-acoustic waves for diagnosis of pneumothorax, a
      collapsed lung. The hypothesis was that the acoustic response of the chest to
      external excitation would change with this condition. In experimental canine
      studies, external acoustic energy was introduced into the trachea via an
      endotracheal tube. For the control (nonpneumothorax) state, it is hypothesized
      that sound waves primarily travel through the airways, couple to the lung
      parenchyma, and then are transmitted directly to the chest wall. In
      contradistinction, when a pneumothorax is present the intervening air presents an
      added barrier to efficient acoustic energy transfer. Theoretical models of sound
      transmission through the pulmonary system and chest region to the chest wall
      surface are developed to more clearly understand the mechanisms of intensity loss
      when a pneumothorax is present, relative to a baseline case. These models predict
      significant decreases in acoustic transmission strength when a pneumothorax is
      present, in qualitative agreement with experimental measurements. Development of
      the models, their extension via finite element analysis, and comparisons with
      experimental canine studies are reviewed.

PMID- 12002876
TI  - Normative voice range profiles of male and female professional voice users.
AB  - Normative voice range profiles (VRP) are calculated for a group of male and
      female teachers, based on 43 and 46 recordings, respectively. All individuals had
      healthy voices. These normative VRPs contain 95% prediction intervals for both
      frequency and intensity. They are based on a series of mathematical
      transformations of the original individual VRPs in order to maintain in the
      normative VRPs the typical oval VRP shape, including the dip between modal and
      falsetto register. The normative VRPs presented are directly applicable in the
      clinical practice of otolaryngologists and speech-language pathologists.

PMID- 12002877
TI  - New visualization technique with a three-dimensional video-assisted
      stereoendoscopic system: application of the BVHIS display method during
      endolaryngeal surgery.
AB  - A three-dimensional video-assisted stereoendoscopic system (3D video system)
      developed by the Shinko Optical Company, Ltd. (Tokyo, Japan), and referred to as
      the binocular vision by horizontal image shifting display method (BVHIS display
      method), has been developed to digitally process ordinary video signals obtained
      with a video camera connected to a direct videolaryngoscope. The three
      dimensional video system provides the surgeon with stereoendoscopic video images
      and enhances the ability of the surgeon to perform delicate endoscopic
      procedures. The three-dimensional video-assisted stereoendoscopic laryngosurgical
      procedure and its underlying principles are described in this paper. A total of
      12 patients with laryngeal lesions causing dysphonia underwent three-dimensional
      video-assisted stereoendoscopic laryngosurgery. Although the video image obtained
      with the BVHIS display method is only pseudo-three-dimensional, this method
      enables the surgeon to perceive both depth perception and realism. We describe a
      surgical procedure using this new visualizing technique and the underlying
      principles of the technique. Preoperative and postoperative evaluations of the
      patients' vocal functions are also described. This system is a useful tool for
      the treatment of laryngeal lesions causing dysphonia.

PMID- 12002878
TI  - Unilateral versus bilateral injections of botulinum toxin in patients with
      adductor spasmodic dysphonia.
AB  - Both unilateral and bilateral thyroarytenoid muscle injections of Botox provide
      effective management of voice symptoms in patients with adductor spasmodic
      dysphonia; however, the preferred injection technique has not been established.
      In this study, 16 patients were treated with unilateral injections (72 injections
      total) and 33 patients were managed with bilateral injections (133 injections
      total). Individual assignments to injection type were based on treatment
      previously received and dose was adjusted according to the patient's previous
      treatment response. An optimal treatment included a benefit lasting 3 months or
      more with side effects lasting 2 weeks or less. Compared to patients receiving
      bilateral injections, those receiving unilateral injections more frequently noted
      a benefit of 3 months or more (p = 0.03), side effects of 2 weeks or less
      duration (p = 0.03), as well as both a 3-month benefit and a 2-week or less side
      effect (p = 0.0004). Injection type had no effect on optimal Botox dosing with
      repeat injections. Successive unilateral injections at the same dose were more
      likely (p = 0.012) than successive bilateral injections to produce the same or
      longer duration of benefit. We conclude that a unilateral injection routine has a
      more optimal and consistent treatment effect/side effect profile.

PMID- 12002879
TI  - The effect of botulinum toxin A on the vocal symptoms of spastic dysarthria: a
      case study.
AB  - The vocal symptoms of spastic dysarthria and spasmodic dysphonia have many
      similar features. Botulinum toxin has been used effectively to treat spasmodic
      dysphonia. This study was designed to determine what vocal changes occur in an
      individual with spastic dysarthria following Botulinum toxin A injection into the
      thyroarytenoid muscles. Measures were obtained preinjection and three times
      postinjection. Acoustic and aerodynamic results were comparable to those reported
      for individuals with spasmodic dysphonia. The most marked change was increased DC
      airflow. Despite persistent breathiness, the participant reported great
      satisfaction with the result, particularly because of her more appropriate
      loudness. In addition, everyday listeners perceived significantly less listener
      burden and more relaxed and pleasant vocal quality postinjection.

PMID- 12002880
TI  - Vocal tremor reduction with deep brain stimulation: a preliminary report.
AB  - Vocal tremor has been a challenging problem for patients and their physicians. In
      some cases, it has been possible to lesson the symptom's tremor through
      medications and/or voice therapy. However, in most cases no good treatment has
      been available. Chronic stimulation of the thalamus has been successful in
      controlling tremors of the upper limb and other portions of the body. Our
      preliminary experience suggests that it may also be helpful in controlling vocal
      tremor.

PMID- 12002881
TI  - Analysis of voice and quantitative measurement of glottal gap after thyroplasty
      type I in the treatment of unilateral vocal paralysis.
AB  - Thyroplasty type I is one of several surgical treatments in which improving the
      voice of unilateral vocal fold paralysis is the ultimate objective. The goal of
      the surgery is the medialization of the paralyzed vocal fold. The purpose of this
      study is to evaluate the effectiveness of thyroplasty type I through acoustical
      analysis, aerodynamic measures, and quantitative videostroboscopic measurements.
      We report on 20 patients with unilateral vocal cord paralysis who underwent
      thyroplasty type I. We performed preoperative and postoperative video image
      analysis (normalized glottal gap area) and computer-assisted voice analysis
      (fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, mean phonation
      time, mean flow rate, mean subglottic pressure) in all patients. The glottal gap
      was significantly reduced after thyroplasty type I. Postoperative voice quality
      was characterized by an improved pitch and amplitude pertubation (jitter and
      shimmer), phonation time (mean phonation time), and subglottic pressure (mean
      subglottic pressure). Thyroplasty type I is an effective method for regaining
      glottal closure and vocal function.

PMID- 12002882
TI  - Perceptual confusions of high-pitched sung vowels.

PMID- 12002883
TI  - Noise-to-harmonics ratio as an acoustic measure of voice disorders in boys.
AB  - This prospective study assessed the efficacy of computerized noise-to-harmonics
      ratio (NHR) to quantify perceptual and endoscopic findings of dysphonia and/or
      structural lesion of the vocal fold. Fifty Brazilian boys without vocal
      complaints were submitted to computerized, perceptual, and endoscopic
      examination. Thirty boys were dysphonic--3 were classified into the grade
      category, 5 into breathiness, 9 into roughness, and 15 into grade/breathiness.
      Vocal fold lesions were observed in 25 boys (17 nodules and 8 cysts). The Mann
      Whitney U test revealed that NHR was significantly higher in boys with a
      structural lesion (p = 0.007) and in boys with dysphonia (p < 0.0001). However,
      according to a logistic regression model, only the occurrence of dysphonia was
      explained by NHR; the risk for having dysphonia increased approximately twice
      (odds ratio = 1.92, 95% confidence interval = 1.3-2.9) with each increase of 0.01
      in NHR. Our results suggest that noise is a useful quantitative index to confirm
      a perceptual diagnosis of dysphonia and to evaluate quantitative changes in a
      dysphonic voice over time. However, we believe that computerized analysis should
      be used as a complement, rather than a substitute, for perceptual evaluation.
      Further studies with a larger sample are required to investigate the relationship
      between noise and lesions of the vocal folds.

PMID- 12002884
TI  - Correcting low-frequency phase distortion in electroglottograph waveforms.
AB  - Dynamic high-pass filtering with a -3 dB frequency that is a factor of ten or
      more below the voice fundamental frequency has a negligible effect on the
      amplitudes of the Fourier components of an EGG waveform. However, such a filter
      can significantly distort the waveform due to distortion in the phase or time
      alignment of these Fourier components. Such high-pass filtering can be introduced
      purposefully to stabilize the waveform by attenuating low-frequency noise, or may
      be an undesired effect of using an amplification or data acquisition system
      designed for acoustic signals. For a given voice fundamental frequency, the
      amount of distortion depends greatly on the order or attenuation characteristics
      of the filter and on the type of EGG waveform. Both a high-order filter and a
      breathy voice tend to increase the amount of distortion. If the characteristics
      of the high-pass filter are known, there are a number of digital filter
      techniques that can be used to reduce the phase distortion. However, it is shown
      that a relatively simple analogue network can also be used to obtain a correction
      that suffices for most applications. If the precise characteristics of the filter
      are not known, the response to a square wave can be used to adjust the
      compensator parameters for an optimal correction.

PMID- 12002885
TI  - Phonetogram changes for trained singers over a nine-month period of vocal
      training.
AB  - Professional vocalists encounter demands requiring voluntary control of
      phonation, while utilizing a considerable range of frequency and intensity. These
      quantifiable acoustic events can be measured and represented in a phonetogram.
      Previous research has compared the phonetograms of trained and untrained voices
      and found significant differences between these groups. This study was designed
      to assess the effects of vocal training for singers over a period of nine months.
      Phonetogram contour changes were examined, with the primary focus on expansion of
      frequency range and/or intensity control. Twenty-one first-year, master's level,
      vocal music students, who were engaged in an intensive vocal performance
      curriculum, participated in this study. Following nine months of vocal training,
      significant differences were revealed in the subjects' mean frequency range and
      minimum vocal intensity across frequency levels. There was no significant
      difference for the mean maximum vocal intensity across frequency levels following
      vocal training.

PMID- 12002886
TI  - Significance of auditory and kinesthetic feedback to singers' pitch control.
AB  - An accurate control of fundamental frequency (F0) is required from singers. This
      control relies on auditory and kinesthetic feedback. However, a loud
      accompaniment may mask the auditory feedback, leaving the singers to rely on
      kinesthetic feedback. The object of the present study was to estimate the
      significance of auditory and kinesthetic feedback to pitch control in 28 students
      beginning a professional solo singing education. The singers sang an ascending
      and descending triad pattern covering their entire pitch range with and without
      masking noise in legato and staccato and in a slow and a fast tempo. F0 was
      measured by means of a computer program. The interval sizes between adjacent
      tones were determined and their departures from equally tempered tuning were
      calculated. The deviations from this tuning were used as a measure of the
      accuracy of intonation. Statistical analysis showed a significant effect of
      masking that amounted to a mean impairment of pitch accuracy by 14 cent across
      all subjects. Furthermore, significant effects were found of tempo as well as of
      the staccato/legato conditions. The results indicate that auditory feedback
      contributes significantly to singers' control of pitch.

PMID- 12002887
TI  - Vocal parameters of aerobic instructors with and without voice problems.
AB  - Aerobic instructors frequently experience vocal fatigue and are at risk for the
      development of vocal fold pathology. Six female aerobic instructors, three with
      self-reported voice problems and three without, served as subjects. Measures of
      vocal function (perturbation and EGG) were obtained before and after a 30-minute
      exercise session. Results showed that the group with self-reported voice problems
      had greater amounts of jitter, lower harmonic-to-noise ratios, and less
      periodicity in sustained vowels overall, but no significant differences in
      measures of perturbation and EGG were found before and immediately after
      instruction. Measures of vocal parameters showed that subjects with self-reported
      voice problems projected with relatively greater vocal intensity and phonated for
      a greater percentage of time across beginning, middle, and ending periods of
      aerobic instruction than subjects with no reported voice problems.

PMID- 12002888
TI  - Velum behavior in professional classic operatic singing.
AB  - The velopharyngeal opening (VPO) is analyzed in 17 professional operatic singers,
      3 high sopranos, 3 sopranos, 2 mezzo-sopranos, 3 tenors, 2 baritones, 2 bass
      baritones, and 2 basses singing the vowels [a, i, u] at middle degree of vocal
      loudness at different pitches throughout their pitch range. Three methods were
      used for detection of a VPO. One was nasofiberscopy, which revealed VPO of
      various shapes in several singers. Another method was recording nasal and oral
      airflow by means of a divided flow mask. These measurements showed a nasal DC
      airflow at least at some pitches in a majority of the singers. A third method was
      a comparison of the level of the fundamental in the nasal and oral airflow
      signals; this level difference was less than 15 dB in cases where a nasal DC
      airflow was observed. Values less than 15 dB were observed in some cases, thus
      suggesting the presence of a VPO. The tokens produced by the singers were
      assessed by an expert panel with respect to nasal quality of the vowel timbre; no
      correlation was found between rated nasal quality and the presence of a VPO.

PMID- 12002889
TI  - Harmful substances on the opera stage: possible negative effects on singers'
      respiratory tracts.
AB  - Objective, quantitative information is lacking in the medical community about
      actual working conditions for professional singers onstage, and moreover, about
      which conditions are safe. Physicians, speech-language pathologists, and speech
      scientists focusing on laryngology should have relevant information about the
      opera as workplace and the medical sequelae of unhealthy environments. We
      describe five toxic substances to which singers presenting to our clinics were
      exposed while working professionally on the opera stage: (1) aromatic
      diisocyanates, (2) penicillium frequentans in cork granulate, (3) formaldehyde in
      cork granulate, (4) cobalt and aluminum (pigment components), and (5) quartz sand
      capable of entering the alveolae. Biological considerations and clinical data for
      some subjects suggest a direct causal link between the exposures and the
      patients' complaints and findings. Our observations suggest that whenever singers
      complain about deleterious conditions such as dry and hot onstage climate or
      suspicion of the presence of harmful substances, the specific conditions existing
      in the theater in question should be investigated. Harmful substances are not
      only poorly tolerated by singers, but also they should be preventable.

PMID- 12002890
TI  - Measurement of characteristic leap interval between chest and falsetto registers.
AB  - A markedly smaller time constant distinguishes a chest-falsetto leap from the
      more usual execution of a sung interval by muscular adjustments in the length and
      tension of the vocal folds. The features of such a chest-falsetto leap are
      examined in detail with respect to F0, peak-to-peak amplitude of the vocal-fold
      contact area signal (EGG), and the closed quotient. A method is proposed to
      standardize and quantify this chest-falsetto leap in the characteristic leap
      interval (CLI), a measure of the separation between the natural registers in a
      given singing voice. The measure is applied to a varied group of experienced
      singers. Preliminary results include a suggested dimorphic pattern with respect
      to sex, with female voices exhibiting smaller CLIs and less individual diversity
      than male voices.

PMID- 12002891
TI  - Strobovideolaryngoscopic findings in singing teachers.
AB  - Professional voice users often present to otolaryngologists and laryngologists
      with specific voice complaints. The contributions of pathologic lesions to the
      patients' vocal complaints are not always clear on examination, and often,
      premorbid examinations of the larynx are not available for review. This study
      examines the incidence of laryngeal pathology among singing teachers. At a
      national convention of singing teachers, volunteers were recruited for a "free
      strobovideolaryngoscopic examination." All volunteers completed a detailed
      questionnaire of their vocal and medical history and underwent
      strobovideolaryngoscopic examination. Strobovideolaryngoscopic examinations were
      completed in 20 volunteers, 7 of whom had voice complaints and 13 of whom
      perceived their voices to be normal. Vocal fold masses were common among the
      asymptomatic singing teachers. Evidence of reflux laryngitis was a common finding
      among both symptomatic and asymptomatic singing teachers. Asymmetries in vocal
      fold hypomobility were more common among those with voice complaints than was the
      presence of vocal fold masses in the population studied.

PMID- 12002892
TI  - The prevalence of Helicobacter pylori infection in benign laryngeal disorders.
AB  - Helicobacter pylori (HP) is an accepted cause of chronic active gastritis and has
      a major causative role in peptic ulcers. It is a gastric carcinogen. Its role in
      nonulcer dyspepsia (NUD) is less clear, yet 50% of patients with NUD are infected
      with HP, and some recent literature demonstrates long-term improvement of
      symptoms following eradication. HP has been investigated in several other organ
      systems, but has not been investigated to any major degree in laryngeal
      disorders, a region that could be directly exposed to the bacterium from
      pharyngolaryngeal reflux. This study represents one arm of a larger study
      designed to investigate such a relationship. Of 101 patients with nonmalignant
      voice disorders presenting to our voice clinics, 54.5% tested positive for the H.
      pylori organism. Of the controls, 47.1% tested positive. When striated into age
      groups of < 45 years, 46-61 years, and > 62 years, and then age-matched with the
      controls, the likelihood of infection with the H. pylori organism was greater in
      both the experimental middle group, and in the middle group when combined with
      the elder group, than in the matched controls, and this difference demonstrated a
      trend approaching statistical significance. This finding is discussed in the
      light of other studies on HP and on gastroesophageal reflex (GER).

PMID- 12002893
TI  - Histologic and rheologic characterization of vocal fold scarring.
AB  - Scarring of the vocal fold causes considerable dysphonia and presents significant
      treatment challenges. A rabbit model was developed to investigate the histologic
      ultrastructure and rheologic properties of the scarred vocal fold lamina propria.
      Eleven rabbit larynges were scarred by means of forcep biopsy. Sixty days
      postoperatively, the rabbits were sacrificed and their vocal folds were
      harvested. Histological analysis of the scarred and normal lamina propria was
      completed for collagen, procollagen, elastin, and hyaluronic acid. Linear
      viscoelastic shear properties of the tissues were also measured, including
      elastic shear modulus and dynamic viscosity. Compared to normal vocal fold lamina
      propria, scarred tissues demonstrated significantly less collagen, an increase in
      procollagen, and a decrease in elastin. Rheologically, both elastic shear modulus
      and dynamic viscosity were significantly higher for the scarred tissues.
      Increased stiffness and viscosity do not appear to result from an increase in
      collagen, but rather appear to be related to the presence of new, disorganized
      collagen scaffolding. Results are interpreted in terms of the possible role of
      interstitial proteins in the etiology of increased stiffness and viscosity, which
      requires further investigation. This animal model should allow for systematic
      future investigations of vocal fold scarring and its treatment.

PMID- 12002894
TI  - Community based cognitive therapy in the treatment of posttraumatic stress
      disorder following the Omagh bomb.
AB  - Studies in academic research centres with selected patients have shown that
      several cognitive behaviour therapies are effective in the treatment of PTSD
      following traumas affecting individuals or small groups. Little information is
      available on the extent to which these positive findings will generalize to more
      routine clinical settings with less selected patients or to a trauma that affects
      a whole community. The present study addresses these generalization issues. A
      consecutive series of 91 patients with PTSD resulting from a car bomb which
      exploded in the centre of Omagh, Northern Ireland in August 1998 were treated
      with cognitive therapy, along lines advocated by Ehlers and Clark (2000). There
      were no major exclusion criteria and 53% of patients had an additional axis I
      disorder (comorbidity). Therapists were NHS staff with heavy caseloads and modest
      prior training in CBT for PTSD. A brief training in specialist procedures for
      PTSD was provided. Patients received an average of eight treatment sessions.
      Significant and substantial improvements in PTSD were observed. Degree of
      improvement was comparable to that in previously reported research trials.
      Comorbidity was not associated with poorer outcome, perhaps because comorbid
      patients were given more sessions of treatment (average 10 vs 5 sessions).
      Patients who were physically injured improved less than those who were not
      physically injured. Overall, the results indicate that the positive findings
      obtained in research settings generalize well to a frontline, non-selective
      service.

PMID- 12002895
TI  - Prediction of psychological reactions to bone density screening for osteoporosis
      using a cognitive-behavioral model of health anxiety.
AB  - Pre-screening measures derived from a cognitive-behavioral theory of health
      anxiety were significant predictors of individual differences in post-screening
      reactions to a health screening procedure, bone densitometry. Predictors included
      specific illness beliefs (vulnerability, severity/consequences, coping and
      treatment) and general health anxiety measures. Three months after a low bone
      mineral density (BMD) result, women with high levels of pre-existing general
      health anxiety gave higher ratings of anxiety about osteoporosis and perceived
      likelihood of developing osteoporosis than women with low levels of preexisting
      health anxiety, even though the two groups' initial ratings had not differed
      significantly. Women with a low BMD result generally showed "minimization" of the
      seriousness of low BMD but women with very high levels of pre-existing health
      anxiety did not. After a high BMD result, highly health anxious women were only
      temporarily reassured. The results were consistent with the cognitive-behavioral
      analysis of health anxiety.

PMID- 12002896
TI  - Over-valued ideas: a conceptual analysis.
AB  - Over-valued ideas are truly a neglected area of psychopathology with few
      experimental studies published. There is a different emphasis in the USA and
      Europe regarding their definition. For authors in the USA an over-valued idea has
      become shorthand for 'poor insight' in the middle of a continuum of obsessional
      doubts to delusional certainty. Compared to negative thoughts, obsessions and
      delusions, they are often more resistant to any treatment. A better understanding
      of over-valued ideas is required if advances are to be made in therapy and for
      the development of appropriate measures to evaluate the efficacy of novel
      treatments. A cognitive behavioural model of over-valued ideas is presented which
      draws upon the philosophical distinction between beliefs and values. It is argued
      that over-valued ideas are associated with idealised values, which have developed
      into such an over-riding importance, that they totally define the 'self' or
      identity of the individual. Idealised values are also characterised by the
      rigidity with which they are held. Such patients are unable to adapt to different
      circumstances and ignore the consequences of acting on their value. This analysis
      leads to a discussion of predictions that can be tested and various strategies
      that can be used in cognitive behaviour therapy.

PMID- 12002897
TI  - Physical health correlates of overprediction of physical discomfort during
      exercise.
AB  - This study sought to determine if overprediction of physical discomfort prior to
      and following exercise was related to a number of self-report and objective
      measures of physical health status in a general population sample. Cross
      sectional findings indicated a significant and specific relation between patterns
      of discomfort overprediction (vs under- or accurate prediction) and negative self
      reported health status and attitudes to exercise, lower levels of physical
      activity, as well as poorer scores for resting heart rate, cardiorespiratory
      fitness and body mass index (but not waist:hip ratio). Females were more likely
      to overpredict discomfort, were less active and had poorer physical health than
      males. The potential usefulness of the prediction match-mismatch paradigm for
      studying exercise-related appraisal processes as proximal determinants of
      physical activity are discussed. Information obtained from such studies could
      prove useful in public health education campaigns aimed at increasing levels of
      physical activity in the general population, particularly among the less active.

PMID- 12002898
TI  - Exposure to physical movement in chronic back pain patients: no evidence for
      generalization across different movements.
AB  - This study investigated whether the effects of exposure to one movement
      generalize towards another dissimilar movement in patients with low back pain.
      Thirty-nine patients (11 male, 28 female; mean age=43.49 yrs) were requested to
      perform two movements twice, i.e. bending forward and straight leg raising.
      During each of the four trials, baseline pain, expected pain and experienced pain
      were recorded. Analyses revealed that patients initially overpredicted pain, but
      after exposure the overprediction was readily corrected. This exposure effect did
      not generalize towards another dissimilar movement. The above pattern of results
      was only characteristic for patients reporting a high frequency of catastrophic
      thinking about pain. Low pain catastrophizers did not overpredict pain. The
      results are discussed in terms of the view that exposure may be better conceived
      of as the learning of exceptions to a general rule.

PMID- 12002899
TI  - Hyperarousal and dissociation: a study of novice skydivers.
AB  - Peritraumatic dissociation describes alterations in awareness that occur during
      or immediately after a trauma. This study investigated a simulated form of
      peritraumatic dissociation by indexing the responses of skydivers (N=100) who
      were participating in their first skydive. Prior to jumping, participants
      completed the Beck anxiety inventory, the Tellegen absorption scale, and ratings
      of predictability and uncontrollability. Immediately after the jump, they
      completed the peritraumatic dissociative experiences questionnaire and the
      physical reactions scale. Responses indicated that the skydive elicited extreme
      anxiety, hyperarousal, and peritraumatic dissociation in a significant proportion
      of skydivers. Multiple regression analyses indicated that hyperarousal, and to a
      lesser extent anxiety, were strongly predictive of peritraumatic dissociative
      reactions. These results are discussed in terms of proposals that peritraumatic
      dissociation is mediated by hyperarousal.

PMID- 12002900
TI  - Prolonged exposure in patients with chronic PTSD: predictors of treatment outcome
      and dropout.
AB  - The present study investigated predictors of treatment outcome and dropout in two
      samples of PTSD-patients with mixed traumas treated using prolonged imaginal
      exposure. Possible predictors were analysed in both samples separately, in order
      to replicate in one sample findings found in the other. The only stable finding
      across the two groups was that patients who showed more PTSD-symptoms at pre
      treatment, showed more PTSD-symptoms at post-treatment and follow-up. Indications
      were found that benzodiazepine use was related to both treatment outcome and
      dropout, and alcohol use to dropout. Demographic variables, depression and
      general anxiety, personality, trauma characteristics, feelings of anger, guilt,
      and shame and nonspecific variables regarding therapy were not related to either
      treatment outcome or dropout, disconfirming generally held beliefs about these
      factors as contra-indications for exposure therapy. It is concluded that it is
      difficult to use pre-treatment variables as a powerful and reliable tool for
      predicting treatment outcome or dropout. Clinically seen, it is therefore argued
      that exclusion of PTSD-patients from prolonged exposure treatment on the basis of
      pre-treatment characteristics is not justified.

PMID- 12002901
TI  - Fear of storms and hurricanes in Antillean and Belgian children.
AB  - The present study assessed fear of hurricanes in children who had been confronted
      with this natural event (i.e., Antillean children, n=161). Their fear levels were
      compared to those of children who are unfamiliar with such an event (i.e.,
      Belgian children, n=185). Antillean children reported significantly higher levels
      of fear of storms than Belgian children did, thus providing support for the
      notion that exposure to dangerous events promotes children's fears of those
      events. Surprisingly, however, Antillean children had lower scores on the
      'Hurricanes' item than Belgian children. Plausibly, differences in how children
      interpreted this item may have accounted for this unexpected finding. That is,
      ratings of Antillean children were probably based on actual experiences with
      hurricanes, whereas scores of Belgian children presumably reflected appraisal of
      threat in case they would be confronted with such an event. Implications of this
      finding for the assessment of childhood fears are briefly discussed.

PMID- 12002902
TI  - Screening for mutations in exons encoding the ligand-binding domain of the LDL
      receptor gene using PCR-CFLP and PCR-SSCP.
AB  - Primary hypercholesterolemia includes both monogenic disorders and polygenic
      conditions. Two well defined monogenic disorders are familial
      hypercholesterolemia (FH) and familial defective apolipoprotein (apo) B-100
      (FDB). Both disorders convey high risk of premature coronary artery disease. FH
      and FDB are caused by mutations in LDL receptor and apo B-100 genes,
      respectively. In the present study, mutations in both genes in Thai subjects with
      primary hypercholesterolemia were screened. For apo B-100 gene, a common mutation
      R3500Q was screened. This mutation was not observed in the patients (n = 45). For
      LDL receptor gene, mutations in the exons encoding the ligand-binding domain were
      screened. By PCR-CFLP analysis, 18 abnormal CFLP patterns in exon 4, the hot spot
      for mutations, were found in patients (n=45). One of the DNA samples with
      abnormal CFLP patterns was previously identified and reported as a possible
      disease-causing mutation, namely D151Y. For the other exons, the screening
      technique was PCR-SSCP. Abnormal SSCP patterns in DNA samples from patients
      (n=20) were found as follows, two in exon 3, one in exon 5 and another one in
      exon 6. Further characterization by DNA sequencing and family studies for these
      abnormal patterns are underway.

PMID- 12002903
TI  - Serum lipoprotein (a) level and restenosis after percutaneous coronary
      intervention.
AB  - Restenosis is regarded as the result of a combination of various pathological
      events. The mechanisms are complex and not completely understood. In this study,
      the authors focused on the lipoprotein (a) (Lp (a)). It is one of the novel risk
      factors in atherosclerotic vascular disease. Numerous clinical studies suggest
      that individuals with elevated blood levels of Lp (a) have been shown to be
      associated with atherosclerotic vascular disease. However, whether a high serum
      concentration of Lp (a) affects restenosis after PCI remains controversial. In
      this study, the relationship between serum Lp (a) levels and restenosis after PCI
      was examined to investigate whether serum Lp (a) levels may be a predictor of
      restenosis after PCI. Of the 100 patients studied, 31 patients (31%) were
      classified as the restenosis group and 69 patients (69%) the non-restenosis
      group. Both groups did not significantly differ in serum concentration of total
      cholesterol, triglyceride, HDL-C, and LDL-C. The mean serum Lp (a) concentration
      in patients with restenosis was 41.50 +/- 34.99 mg/dL compared with a mean serum
      Lp (a) concentration of 29.87 +/- 25.47 mg/dL in those without restenosis. There
      was no statistical significance of Lp (a) level between the restenosis and non
      restenosis groups (p=0.06). In healthy subjects, the normal reference range of
      serum Lp (a) concentration is below 30 mg/dL. From this reference, if a cut off
      point of serum Lp (a) concentration equal to 30 mg/dL or above to identify high
      Lp (a) level group was used. High serum Lp (a) level was established in 15
      patients with restenosis versus 21 patients without restenosis. From this cut off
      point of serum Lp (a) level, the authors did not find a correlation between serum
      Lp (a) level and the restenosis group. (p=0.08).

PMID- 12002904
TI  - Homocysteine and restenosis after percutaneous coronary intervention.
AB  - Numerous clinical studies in Western and Asian countries suggest that individuals
      with elevated blood levels of homocysteine have an increased risk of
      atherosclerosis, myocardial infarction, cerebral infarction, and deep vein
      thrombosis. Homocysteine is also known to induce both atherogenic and
      thrombogenic mediators in cultured vascular cells so that homocysteine may
      influence the damage of endothelial cells, promote smooth muscle cell growth,
      induce atherogenic mediators and thrombus formation after coronary angioplasty.
      The association between homocysteine and restenosis after percutaneous coronary
      intervention (PCI) has been discussed. In this study, the relationship between
      plasma homocysteine levels and restenosis after PCI to investigate whether plasma
      homocysteine levels may be a predictor of restenosis after PCI was examined. One
      hundred consecutive patients who underwent successful PCI were enrolled and
      plasma homocysteine level was measured in all patients prior to PCI. Plasma for
      homocysteine level was obtained in 99 of 100 patients who had angioplasty. The
      mean plasma homocysteine concentration in the enrolled patients was 13.61 +/-
      6.04 micromol/L. The minimum and maximum of plasma homocysteine were 4.40
      micromol/L and 50.00 micromol/L, respectively. In healthy subjects, the normal
      reference range of homocysteine level is 5-15 micromol/L However, recent data
      suggest that some patients may be at increased cardiovascular and cerebrovascular
      risk at levels as low as 12 micromol/L. For this reason, both cut off points of
      homocysteine level > or = 15 micromol/L or > or = 12 micromol/L to identify the
      high homocysteine level group were used. Of 99 patients, high homocysteine level
      (> or = 15 micromol/L) was established in 9 patients with restenosis versus 20
      patients without restenosis. If the cut off point of homocysteine level > or = 12
      micromol/L was used, high homocysteine level was established in 14 patients with
      restenosis versus 39 patients without restenosis. From both cut off points of
      homocysteine level, there was no correlation between plasma homocysteine level
      and the restenosis group. (p>0.05).

PMID- 12002905
TI  - Serum magnesium in Thai coronary artery disease patients.
AB  - Hypomagnesemia or magnesium (Mg) deficiency has been hypothesized to play a role
      in coronary artery disease (CAD). The authors aimed to evaluate serum Mg
      concentration in 100 CAD patients compared with 100 healthy controls. Mean values
      of serum Mg level in CAD and the control group were 2.14 +/- 0.39, 2.24 +/- 0.3
      mg/dL respectively (P=0.052). The prevalence of Mg deficiency was 12 per cent in
      the CAD patients, and 5 per cent in the control group (odds ratio=2.59, 95%
      confident interval = 0.88-7.65, P=0.063). There was no significant difference in
      the serum Mg level between the 2 groups, although it tended to be lower in CAD
      patients. The prevalence of Mg deficiency did not differ significantly between
      the study group, however, it tended to be higher in CAD patients. These findings
      demonstrated that CAD patients may be associated with Mg deficiency, and
      contribute to the pathogenesis of CAD or acute thrombosis. Following this
      evidence, Mg treatment may be necessary in CAD patients with Mg deficiency or
      acute myocardial infarction (AMI).

PMID- 12002906
TI  - Chronic infections and atherosclerosis.
AB  - The established risk factors for atherosclerosis such as hypertension, smoking,
      diabetes mellitus, hyperlipidemia, and hyperhomocysteinemia do not explain
      clinical and epidemiological features of coronary heart disease (CHD). The role
      of infectious disease as a CHD risk factor may partly explain these features.
      Chronic infection with various microorganisms, particularly, Chlamydia
      pneumoniae, Cytomegalovirus (CMV) and Helicobacter pylori may play a role in
      etiological factors, linking inflammation and atherogenesis. Results from
      epidemiological studies, pathology of atherosclerotic plaques, animal studies,
      molecular biology and clinical antibiotic trials indicated a positive association
      between C. pneumoniae infection and CHD. Chronic infection might also influence
      preexisting plaque by enhancing T cell activation, which participate in
      destabilization of intimal cap. However, the exact nature of pathophysiological
      link between the organisms and CHD remains to be elucidated. Future antibiotic
      interventional studies may help to further clarify the role of chronic infection
      and inflammation in CHD.

PMID- 12002907
TI  - Rapid detection of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells
      of coronary artery disease patients by real-time fluorescence PCR.
AB  - Several recent reports including serological, pathological and animal studies
      have associated Chlamydia pneumoniae with coronary artery disease (CAD). In order
      to establish whether chronic C. pneumoniae infection is linked to coronary artery
      disease, clinical intervention trials may be needed. However, to detect eligible
      patients with persistent infection, a reliable diagnostic marker must be
      developed for identifying cases and assessing efficacy of antichlamydial therapy.
      Moreover, the prevalence of circulating C. pneumoniae DNA in CAD patients varied
      widely from previous reports. A real-time PCR has been established by using HL-1
      and HR-1 primer to amplify 437 base pairs product. Confirmation of the product
      was performed on LightCycler by melting curve analysis of detection probes
      labeled with LC-Red705. Ninety-five angiographically confirmed CAD patients and
      104 normal, healthy volunteers were recruited. The mononuclear cell layer was
      separated from collected blood and rapid, single step real-time PCR was used to
      detect C. pneumoniae DNA. C. pneumoniae DNA in peripheral blood mononuclear cells
      (PBMC) was found in 17 per cent of 95 CAD patients and 1 per cent of 104 normal
      healthy volunteers (odds ratio 20.86, 95% confidence interval 2.71 - 160.67, p <
      0.0001). There was no association between C. pneumoniae DNA in PBMC and
      serological status. The rapid, real-time PCR showed a clear-cut result between
      positive and negative cases. PBMC-based real-time PCR may be a useful tool for
      identifying subjects carrying C. pneumoniae in the circulation or in the vascular
      wall as well. It will be a specific indicator of current infection and will be
      used as a marker for assessing the microbiological efficacy of antichlamydial
      therapy in clinical intervention trials.

PMID- 12002908
TI  - Roxithromycin in prevention of acute coronary syndrome associated with Chlamydia
      pneumoniae infection: a randomized placebo controlled trial.
AB  - The role of Chlamydia pneumoniae infection in precipitating acute coronary
      syndrome (ACS) is unclear. Some studies have indicated that intervention with
      macrolide antibiotics might reduce coronary events in patients with ACS. A double
      blind, randomized, placebo-control trial was conducted on 84 ACS patients.
      Patients were randomized to 30 days of treatment with roxithromycin (150 mg,
      twice daily) or matching placebo. The follow-up period was 90 days, and the
      primary clinical end point included cardiovascular death, unplanned
      revascularization and recurrent angina/MI. Anti-C. pneumoniae IgG positive in 24
      of 43 (55.8%) patients in the roxithromycin group and 23 of 41 (56.1%) patients
      in the placebo group. Anti-C. pneumoniae IgA positive in 20 of 43 (46.5%)
      patients in the roxithromycin group and 13 of 41 (31.7%) patients in the placebo
      group. Thirty-three cardiac events occurred (2 cardiovascular deaths, 9 CABG, 12
      PTCA and 10 recurrent angina/MI) with 17 events in the roxithromycin group and 16
      events in the placebo group. There was no significant difference of cardiac
      events between the roxithromycin and placebo groups. The present study suggests
      that antibiotic therapy with roxithromycin is not associated with reduction of
      cardiac events as reported by other investigators. However, therapeutic
      interventions may need to be specifically targeted to a group of patients who are
      confirmed with chronic C. pneumoniae infection.

PMID- 12002909
TI  - Inexpensive, rapid and convenient PCR-minigel SSCP protocol for polymorphisms and
      mutations analyses of LDL receptor gene.
AB  - Hypercholesterolemia has been recognized as a major risk factor of
      atherosclerosis and coronary artery disease. The elevation in plasma low density
      lipoprotein (LDL) cholesterol is frequently due to genetic alteration at the
      genetic locus specifying the LDL receptors, leading to defective catabolism of
      LDL. In order to facilitate the molecular diagnosis of LDL receptor disorder,
      single strand conformation polymorphism (SSCP) analysis of polymerase chain
      reaction (PCR) amplified genomic DNA fragments has become a simple and sensitive
      screening method for identification of DNA polymorphisms and mutations in LDL
      receptor gene prior to DNA sequencing. In addition, SSCP patterns can be detected
      by silver staining to avoid hazardous radioactive material or other costly
      nonradioactive detection techniques. However, the original SSCP protocol is
      generally large-formatted, which is both time and reagents consuming as well as
      cumbersome. Minigel SSCP protocols have thus been devised but they involve,
      although commercially available, costly precast gels. We describe here a
      nonradioactive PCR-minigel SSCP protocol which is sensitive, inexpensive, rapid,
      reproducible and manually convenient. The results in this study demonstrate that
      minigel-SSCP (gel size: 10 cm x 7.3 cm x 0.075 cm) can detect conformation
      polymorphisms in PCR-fragments with a comparative sensitivity to large gel SSCP
      (gel size: 30 cm x 40 cm x 0.04 cm) as exemplified by the SSCP analyses of exon
      13 of the LDL receptor gene. For minigel SSCP, the reagents for gel components
      and silver staining are reduced approximately 9 times and 10 times, respectively.
      For electrophoresis, electrical power is also reduced 10 times. This improved
      technique can become routinely used for molecular diagnosis of LDL receptor
      defect as well as for other genetic disorders.

PMID- 12002910
TI  - Serum concentrations of lipids and apolipoprotein E in angiographically defined
      coronary artery disease patients.
AB  - Apolipoprotein (apo) E is an important component of plasma lipoproteins and
      influences lipoprotein metabolism through its action as a receptor ligand. The
      association of serum apo E concentrations and coronary artery diseases (CAD) was
      investigated in 100 CAD patients (71 men, 29 women, mean age 62.0 years) and 155
      healthy volunteers (87 men, 68 women, mean age 50.6 years). Patients with CAD had
      lower serum apo E concentrations (5.1+1.3 mg/dL) than the healthy volunteers
      (5.9+1.8 mg/dL, p <0.001). There were no significant differences between the
      number of disease vessels and the concentration of serum apo E. Serum apo E
      concentrations may have an anti-atherosclerotic effect and the serum apo E levels
      could be a useful parameter for defining cardiovascular risk factor.

PMID- 12002911
TI  - Homozygous DNA variants in exon 9 of the LDL receptor gene in a Thai patient with
      primary hypercholesterolemia phenotype.
AB  - Mutation in low density lipoprotein (LDL) receptor gene causes an inherited
      primary hypercholesterolemia namely familial hypercholesterolemia (FH). In this
      study, 46 Thai patients with primary hypercholesterolemia were screened for
      mutations in exon 9 of the LDL receptor gene by polymerase chain reaction
      restriction fragment length polymorphism (PCR - RFLP). The analysed fragment was
      224 bp in length. According to the published cDNA sequence, exon 9 of the LDL
      receptor gene contains several hypermutable CpG dinucleotides. Three of these
      sites are Hpa II recognition sites. PCR product of exon 9 obtained from
      amplification of wild-type DNA sample would yield four fragments after Hpa II
      digestion. The expected sizes of these restriction fragments were 15, 30, 40 and
      139 bp. All normocholesterolemic subjects (n = 33) showed normal RFLP. However,
      in one patient (72 year old female), abnormal RFLP from Hpa II digestion of the
      amplified exon 9 was observed, i.e., a fragment of 70 bp and another one smaller
      than 139 bp. Such RFLP reflects that exon 9 of both alleles of the LDL receptor
      gene in this patient lost one and gained one Hpa II site. It is interesting that
      this patient, eventhough harbouring two mutations on both alleles of the LDL
      receptor gene (presumably homozygous genotype of FH), apparently revealed lipid
      levels of heterozygous phenotype of FH without symptoms of coronary artery
      disease. It has yet to be proved whether these genetic variations are disease
      related mutations or presumably common DNA polymorphisms.

PMID- 12002912
TI  - The effects of COX-metabolites on cyclooxygenase-2 induction in LPS-treated
      endothelial cells.
AB  - Cyclooxygenase (COX) is the first enzyme in the pathway in which arachidonic acid
      is converted to PGs, also called COX-metabolites. COX exists as COX-1 and COX-2
      isoforms. Each COX-metabolite has different characters and functions. The amounts
      of each COX-metabolite produced in cells are also different depending on cell
      type and mitogen stimulated cells. These were thought to be autoregulation among
      COX-metabolites. Here, we have investigated the effects of COX-metabolites, such
      as PGI2, PGE2, PGF2alpha and U44069, on the induction of COX-2 in human umbilical
      vein endothelial cells (HUVEC) treated with LPS (1 microg/ml). COX activity was
      measured by the production of 6-keto-PGF1alpha, PGE2, PGF2alpha and TXB2 in the
      presence of exogenous arachidonic acids (10 microM for 10 min) using enzyme
      immunoassay (EIA). COX-1 and COX-2 protein was measured by immunoblotting using
      specific antibody. PGI2, PGE2, PGF2alpha or U44069, did not affect on basal COX
      activity in untreated HUVEC (24 h incubation). Untreated HUVEC contained COX-1
      protein but not COX-2 protein. When HUVEC were treated with LPS (1 microg/ml for
      24 h), COX activity and COX-2 protein was increased in a dose dependent manner.
      The increased COX activity in LPS (1 microg/ml) treated HUVEC was inhibited with
      PGE2 (0.03, 0.3 or 3 microM), but not PGI2, PGF2alpha or U44069, in a dose
      dependent manner. Similarly, COX-2 protein expression in LPS treated HUVEC was
      also inhibited with PGE2, but not PG2, PGF2alpha or U44069, in a dose dependent
      manner. These results suggested that PGE2, but not PGI2, PGF2alpha or TXA2 is a
      key in feedback regulation of COX-metabolites produced in HUVEC.

PMID- 12002913
TI  - The activation of platelet aggregation by human cholangiocarcinoma cells is
      mediated through thrombin receptor.
AB  - Tumor cell induced platelet aggregation (TCIPA) played an importance role in
      early state of thrombosis in cancer patients. In addition, TCIPA was recognized
      as one important step in metastatic cascade. Cholangiocarcinoma, one of the most
      common cancers in the north-eastern part of Thailand, associated with thrombosis
      was reported. The authors investigated the effects of cholangiocarcinoma cells on
      platelet function as measured by platelet aggregation. Primary human
      cholangiocarcinoma (HuCCA) cells were established in our laboratory. Cells were
      cultured as standard techniques and grown to confluence until used, after which
      cells were replaced with fresh medium (Dulbeco Modified Eargle's Medium, DMEM)
      without serum for 24, 48 and 72 h. Then, the conditioned medium (CM) was
      collected. CM (24, 48 and 72 h) from HuCCA failed to induce platelet aggregation,
      whereas, HuCCA pellets induced platelet aggregation and potentiated platelet
      aggregation induced by submaximal concentration of thrombin. Interestingly,
      platelet aggregation induced by HuCCA was inhibited by hirudin (thrombin receptor
      antagonist; 10, 20 and 40 U) in a dose dependent manner. Thus, cholangiocarcinoma
      cells can induce platelet aggregation in a direct tumor cell-platelet contact via
      thrombin receptor. Therefore, the use of antiplatelet agents especially via
      thrombin receptors may help to prevent TCIPA or metastasis by CCA.

PMID- 12002914
TI  - Prevalence of hyperhomocysteinemia in normal healthy Thai subjects.
AB  - The concentration of circulating total homocysteine is a sensitive marker of
      inadequate folate and vitamin B12 status. The elevations of plasma homocysteine
      concentration are associated with an increased risk of vascular disease. The
      primary goals of this study were to identify plasma homocysteine concentrations
      in Thai residents and to test for differences in homocysteine levels among sex
      and age categories. The authors measured plasma total homocysteine concentrations
      in 3,345 Shinawatra employees (1,133 males, 2,212 females aged between 20-65
      years) by using fluorescence polarization immunoassay (FPIA) method. The mean
      plasma homocysteine concentrations of males and females were 11.495 and 8.547
      micromol/L respectively. Plasma homocysteine concentrations were significantly
      lower in females than in males (p < 0.0001). The age-specific plasma homocysteine
      levels were lower in females than in males for each group, but the levels of each
      group was not significantly different both in males and females. When more than
      12 micromol/L was used as the cut-off value, it was found that 33.6 per cent of
      males and 6.69 per cent of females were classified as hyperhomocysteinemia
      subjects. The authors concluded that the prevalence of hyperhomocysteinemia in
      Thai males is more common than in females. Further investigation should be done
      to clarify the association between serum folate, vitamin B12, vitamin B6
      concentrations and plasma homocysteine concentration.

PMID- 12002915
TI  - Serum nitric oxide levels in patients with coronary artery disease.
AB  - Nitric oxide (NO) plays a pivotal role in the pathophysiology of coronary artery
      disease. The roles of NO are not only physiological but also pathological in the
      cardiovascular system. An inappropriate release of NO has been linked to the
      pathogenesis of CAD. The authors investigated whether serum NOx (nitrate and
      nitrite), a stable end product of NO, level was related to patients with coronary
      artery disease. The blood chemistry, such as cholesterol, triglyceride, LDL-C,
      HDL-C and blood sugar, was also measured in comparison with serum NOx. Serum NOx
      was measured in samples from 20 healthy controls, 20 angina patients without
      angiographic evidence of coronary lesions (CAG) and 20 angina patients with
      angiographic evidence of coronary lesions (CAD) by using modified Griess
      reaction. The mean serum NOx levels in the CAD groups was higher than CAG and
      control groups (41.3 +/- 5.5, 32.7 +/- 3.9 and 25.7 +/- 3.5 micromol/L,
      respectively). NOx levels in the CAD group was only significantly higher than the
      control groups (p < 0.05) but not the CAG groups. There were no significant
      differences of NOx levels in all age groups. In the CAD group, women showed
      significantly higher NOx levels than men (64.0 +/- 7.5 and 29.0 +/- 4.7 microl/L,
      respectively, p < 0.05). Interestingly, the mean serum NOx levels in the CAD
      groups was significantly higher in a group of abnormal lipid profiles
      (cholesterol, triglyceride, LDL-C) and blood sugar than in a group of normal
      profiles. The results suggested that there was an increased NOx levels in
      patients with coronary artery disease and much higher in patients with multiple
      underlying conditions such as hyperlipidemia and hyperglycemia. Thus, the
      measurement of the NOx levels at different times may help to monitor the state
      and severity of coronary artery disease.

PMID- 12002916
TI  - The analysis of peri-tumor necrosis following the subcutaneous implantation of
      autologous tumor cells transfected with an episome transcribing an antisense
      insulin-like growth factor 1 RNA in a glioblastoma multiforme subject.
AB  - A subject inflicted with glioblastoma multiforme who received partial tumor
      resection and radiotherapy was recruited for an ex vivo gene therapy protocol
      using irradiated autologous tumor cells that had been engineered to suppress the
      expression of insulin-like growth factor I as the tumor vaccine. After
      subcutaneous injection for 8 weeks, the subject developed peri-tumor necrosis
      with mass effect. The authors wondered whether this event could have resulted
      from the tumor vaccine. The tissue section bordering the necrotic tumor tissue to
      the viable normal tissue was examined for nature of any infiltrated cells and
      their activities. Lymphocytes, macrophages, and a small number of neutrophils
      diffused into the necrotic tumor tissue were found. The infiltrated lymphocytes
      consisted of both CD4+ and CD8+ T cells. The functional activity of these
      lymphocytes was demonstrated by the active production of interferon y and tumor
      necrosis factor alpha based on the respective immunofluorescent staining
      localized to these cells. This finding is compatible with the proposed mechanism
      underlying the tumor vaccination. However, the contribution of radiation
      treatment to this event cannot be clearly ruled out.

PMID- 12002917
TI  - Intravenous induction agents: ketamine.

PMID- 12002918
TI  - Monitoring neuromuscular transmission.
AB  - Persistent neuromuscular blockade is not uncommon in the recovery room and
      contributes to postoperative morbidity and possibly mortality. The use of
      neuromuscular monitoring and intermediate rather than long-acting neuromuscular
      blocking drugs have been shown to reduce its incidence. Clinically available
      methods of detecting and quantitating neuromuscular blockade are reviewed. The
      writer concludes that such monitoring should be routine when neuromuscular
      blocking drugs are used.

PMID- 12002919
TI  - Pharmacological principles of antibiotic prescription in the critically ill.
AB  - The goal of antimicrobial prescription is to achieve effective drug
      concentrations. Standard antimicrobial dosing regimens are based on research
      performed often decades ago and for the most part with patients who were not
      critically ill. More recent insights into antibiotic activity (e.g. the
      importance of high peak/MIC ratios for aminoglycosides and time above MIC for
      beta-lactam antibiotics), drug pharmacokinetics (e.g. increased volume of
      distribution and altered clearances) and the pathogenesis of sepsis (e.g. third
      space losses and altered creatinine clearances) have made re-evaluation of dosing
      regimens necessary for the critically ill. The inflammatory response associated
      with sepsis results in a rapid decrease in serum albumin levels, large fluid
      shifts and third space losses, initially with a high cardiac output. In turn
      these changes result in increased creatinine clearance and increased renal drug
      clearance. Unless these effects are offset by ensuing renal and/or hepatic
      impairment, with subsequent drug accumulation, antibiotic levels may be too low
      for optimal efficacy. The institution of continuous renal replacement therapy
      separately affects antibiotic clearances, and therefore dosing, even further.
      This article reviews relevant literature and offers principles for more effective
      and appropriate antibiotic dosing in the critically ill, based on the
      pharmacokinetic and pharmacodynamic principles of the main antibiotic groups
      (aminoglyosides, glycopeptides, beta-lactams, carbapenems and quinolones) and
      knowledge of the pathophysiology of the inflammatory response syndrome. Finally
      it also provides some guidance on the basic principles of drug prescription for
      patients receiving continuous renal replacement therapy.

PMID- 12002920
TI  - Tracheobronchial injury secondary to blunt chest trauma: diagnosis and
      management.
AB  - Tracheobronchial injury is an uncommon complication in blunt chest trauma. The
      typical clinical features include haemoptysis, dyspneoa, and air leak.
      Tracheobronchial injury occurs after high energy impact and is commonly
      associated with injuries of other vital organs. If tracheobronchial injury is
      undetected and left untreated, it may cause persistent air leak which can render
      ventilation difficult and inefficient. Diagnosis of tracheobronchial injury
      should be made and confirmed by flexible bronchoscopy. The essence of airway
      management is to bypass the lesion by means of endobronchial intubation to the
      healthy bronchus with a single-lumen or double-lumen endotracheal tube. Such
      manoeuvres can also facilitate surgical access if thoracotomy is indicated.
      Taking into account the size of the lesion and the resulting respiratory status,
      surgical reconstruction of the injured airway is often necessary. More severe
      injury may even require lobectomy or pneumonectomy. Late complications of
      untreated tracheobronchial injury include bronchial stenosis, recurrent pneumonia
      and bronchiectasis. Prompt diagnosis and treatment generally lead to good
      functional recovery.

PMID- 12002921
TI  - The effect of anaesthetic technique on postoperative nausea and vomiting after
      day-case gynaecological laparoscopy.
AB  - Gynaecological surgery is of high emetogenic potential and both total intravenous
      anaesthesia (TIVA) and prophylactic antiemetic therapy may reduce the incidence
      of postoperative nausea and vomiting (PONV). We studied 144 patients scheduled
      for day-case gynaecological laparoscopy in a randomized trial comparing balanced
      inhalational anaesthesia and prophylactic dolasetron (group I+D) with propofol
      TIVA and dolasetron (group T+D) or TIVA alone (group T). The primary outcome of
      "complete response" (no vomiting, no treatment for PONV) was not significantly
      different among groups (34%, 51%, 32%; groups I+D vs T+D vs T, P=0.12). During
      the first hour after surgery, group I+D had nausea of greater severity (P<0.03).
      During hospital admission, group T had more vomiting (P<0.03). From discharge
      until 24 hours postoperatively, 55% of group I+D experience nausea and 38%
      vomited. The incidence and severity of nausea were significantly lower in the
      TIVA groups (P<0.04 and <0.05 respectively). There were no significant
      differences between groups T+D and T, although comparing all groups the complete
      response rate was highest and the post-discharge incidence and severity of nausea
      lowest in group T+D. In conclusion, propofol TIVA, with or without dolasetron,
      reduced postoperative nausea, but not perioperative vomiting or antiemetic
      requirement, when compared with inhalational anaesthesia plus dolasetron.

PMID- 12002922
TI  - Tenoxicam 20 mg or 40 mg after thoracotomy: a prospective, randomized, double
      blind, placebo-controlled study.
AB  - Forty-five adults undergoing thoracotomy were randomized to receive placebo,
      tenoxicam 20 mg or tenoxicam 40 mg IV during chest wall closure. All patients
      received intraoperative fentanyl and intercostal blocks followed by morphine by
      patient-controlled analgesia. Patient numbers 13 to 45 also received thoracic
      epidural analgesia by continuous infusion of bupivacaine 0.125%, patient numbers
      25 to 45 having fentanyl 2 microg/ml added to the epidural infusion. Efficacy
      parameters and adverse reactions were assessed over the first 24 hours
      postoperatively. On a 100 mm visual analogue scale, mean (SD) pain at rest
      (adjusted area under curve for hours 1 to 24) was 25.8 (12.5), 17.4 (14.8) and
      16.5 (13.3) mm for groups receiving placebo, 20 mg and 40 mg tenoxicam,
      respectively (ANOVA: P<0.05). There were no significant differences between study
      groups postoperatively in pain on coughing, opioid consumption, blood gas
      measurements, nausea, vomiting, sedation, blood loss, haemoglobin or serum
      creatinine. One patient in each tenoxicam group reported epigastric pain, rated
      moderate. These data support the inclusion of tenoxicam 20 mg IV in the
      management of pain at rest for patients undergoing thoracotomy, but do not show
      additional benefit for a higher dose.

PMID- 12002923
TI  - The effect of selective brain cooling on intracerebral temperature during
      craniotomy.
AB  - In this study we investigated the effect of topical application of cool
      irrigation fluid on brain tissue temperature during craniotomy. Eight patients
      were given a standard general anaesthetic for craniotomy. Distal oesophageal and
      nasopharyngeal temperatures were measured continuously and systemic normothermia
      was maintained. A sterile needle temperature probe was inserted 18 mm into the
      cerebrum to measure brain temperature. Brain temperatures were recorded for five
      minutes while the brain was irrigated with 1000 ml of normal saline at a
      temperature of 30 degrees C. Measurement continued until the brain temperature
      returned to baseline. The mean maximum decrease in cerebralparenchymal
      temperaturefollowing irrigation was 1.6 +/- 0.5 degrees C (P<0.01). The average
      time to return to baseline temperature after cessation of irrigation was 5.3 +/-
      1.5 minutes. Cooling the brain has a marked protective effect after brain injury,
      but systemic hypothermia can produce significant harmful effects. This study
      demonstrates that the use of cool irrigation fluid during neurosurgery is a
      simple and effective method of cooling the brain whilst minimizing the use of
      systemic hypothermia.

PMID- 12002924
TI  - Propofol and midazolam versus propofol alone for sedation following coronary
      artery bypass grafting: a randomized, placebo-controlled trial.
AB  - The aim was to compare the efficacy and side-effects of propofol combined with a
      constant, low dose of midazolam versus propofol alone for sedation. In a
      prospective, randomized and double-blinded study, 60 male patients scheduled for
      elective coronary bypass grafting were enrolled. Postoperatively, patients were
      stratified to receive either a continuous intravenous infusion of midazolam 1
      mg/h or placebo. Target Ramsay sedation score was 3 to 5 corresponding to
      conscious sedation. An intention-to-treat design for propofol was performed to
      reach target sedation. Efficacy of sedation was statistically significantly
      higher in the group midazolam + intention-to-treat with propofol compared with
      the group placebo + intention-to-treat with propofol (91% vs 79%; P=0.0005). Nine
      of 27 patients in the midazolam group (33.4%) and nine of 26 patients in the
      placebo group (34.6%) needed no supplementary propofol. Weaning time from
      mechanical ventilation was longer in the midazolam group whether or not they
      required supplemental propofol when compared with placebo group (all: 432 +/- 218
      min vs 319 +/- 223 min; P=0.04; supplementary propofol: 424 +/- 234 min vs 265 +/
      175 min; P=0.03). The cumulative number of patients remaining intubated was
      significantly higher in the group midazolam + propofol compared with the group
      placebo + propofol (P=0.03). In conclusion, target sedation is reached slightly
      more often by the co-administration of propofol and a low dose of midazolam, but
      weaning time from mechanical ventilation is prolonged by the co-administration of
      propofol and a low dose of midazolam.

PMID- 12002925
TI  - Inhibition of bacterial growth by lignocaine in propofol emulsion.
AB  - Contamination of propofol, in an emulsion formulation, has been associated with
      infective complications. Local anaesthetics,some of which are known to have
      antibacterial properties, are frequently added to the solution to reduce pain on
      injection. We examined the growth rates of E. coli, S. aureus, S. epidermidis and
      P. aeruginosa in propofol with and without lignocaine 0.1%-2% after incubation
      for 2, 5 and 24 hours at 37 degrees C. Growth of microorganisms in each solution
      was compared by counting the number of colony forming units (CFU). Propofol
      supported the growth of all microorganisms. An increase in the number of CFUs was
      observed in all drug combinations 2, 5 and 24 hours after inoculation except for
      S. aureus (P<0.05). No difference was found in CFU numbers between 2 and 5 hours
      for this microorganism. With E. coli, a significant decline in colony counts was
      observed in mixtures of 1% and 2% lignocaine (P<0.05). With the other
      microorganisms only 2% lignocaine showed a significant reduction in the number of
      CFUs (P<0.05). We conclude that lignocaine in recommended clinical doses (0.05%
      0.1%) did not exhibit adequate antibacterial activity to prevent infective
      complications.

PMID- 12002926
TI  - Theoretical aspects of P-glycoprotein mediated drug efflux on the distribution
      volume of anaesthetic-related drugs in the brain.
AB  - P-glycoprotein in the membranes of endothelial cells actively transports some
      drugs out of the brain. The theoretical effect of P-glycoprotein mediated drug
      efflux on the cerebral distribution volumes of drugs was examined, with
      particular emphasis on anaesthetic-related drugs (often characterized by moderate
      to high permeability across the blood brain barrier due to their lipophilicity
      and intermediate molecular weight). An analytical equation for the cerebral
      distribution volume in the presence of the efflux was derived, and validated by
      modelling the same system using differential equations. The efflux was shown to
      lower both the membrane and intracellular drug concentrations in parallel, and to
      reduce the time required for brain:blood equilibration. The net effect of the
      efflux was governed by the ratio of the P-glycoprotein drug clearance from the
      membrane (Pcl) and the permeability of the membrane (PS). It was therefore a
      balance between the rate that a drug could be pumped out of the membrane by the
      efflux system, and the rate that the drug leaked back in due to the permeability
      of the membrane for the drug. The effect of the efflux was therefore more
      pronounced for drugs with membrane-limited cerebral kinetics (e.g. morphine), but
      was nevertheless significant for drugs with more flow-limited kinetics (e.g
      fentanyl). The cerebral distribution volume was also influenced by the free
      fraction in blood and the free fraction in the intracellular space in the
      conventional manner. There are no theoretical limitations to the P-glycoprotein
      system influencing the cerebral distribution volume of moderately lipophilic
      anaesthetic-related drugs.

PMID- 12002927
TI  - The effect of neuromuscular blockade on oxygen supply, consumption, and total
      chest compliance in patients with high oxygen requirements undergoing mechanical
      ventilation.
AB  - We investigated the effects of neuromuscular blockade with atracurium on oxygen
      consumption, oxygen delivery and total chest compliance in 20 sedated intensive
      care patients who required mechanical ventilation with an inspired oxygen
      fraction of at least 0.6. The reverse Fick method was used to measure oxygen
      consumption. Total chest compliance was measured from the ventilator
      pneumotachograph and pressure transducer. Measurements were made before
      neuromuscular blockade, at a standard level of neuromuscular blockade, and after
      demonstrated recovery of neuromuscular function. There was no statistical
      difference in any of the parameters measured. However there were large changes in
      oxygen consumption (range -35% to +17%) and total chest compliance (range -19.7%
      to +9.7%) in individuals. We conclude that in the setting of critical
      oxygenation, neuromuscular blockade cannot be assumed to reduce oxygen
      requirements or improve total lung compliance. If, however, neuromuscular
      blockade is selected as an adjunct to therapy, we recommend that the indices of
      oxygenation are calculated.

PMID- 12002928
TI  - Simulation of potassium extraction by continuous haemodiafiltration.
AB  - Prediction of potassium extraction rates by continuous haemodiafiltration (CHDF)
      is useful for safe management of potassium levels in patients with hyperkalaemia.
      For this purpose, we developed a formula to predict the quantity of potassium
      extracted by CHDF. We hypothesized that potassium concentration in efflux
      dialysate was completely saturated by the influx blood, and potassium
      concentration in efflux blood was calculated based on this hypothesis. To check
      the accuracy of the calculation, potassium concentration was measured in efflux
      blood, and values were compared to predicted concentrations. Predicted potassium
      concentrations demonstrated good correlation to the measured values (95%
      confidence range, -0.32 to 0.58 mmol/l). These results confirmed that our
      hypothesis is applicable to clinical use of CHDF. Based on our observations, we
      created a formula to accurately predict the amount of potassium (dK) extracted by
      CHDF: dK=(Cb-Cd)xQd+CbxQf-CsxQs (Cb: plasma potassium concentration; Cd:
      potassium concentration in a dialysate; Cs: potassium concentration in the
      replacement fluid; Qd: dialysis rate; Qf: filtration rate and Qs: infusion rate
      of replacement fluid).

PMID- 12002929
TI  - Association of serum albumin concentration and mortality risk in critically ill
      patients.
AB  - In this study we aimed to examine the association between serum albumin
      concentration and mortality risk in critically ill patients. We retrospectively
      studied 1003 patients admitted to ourIntensive Care Unit (ICU) over an 18-month
      period. Serial albumin measurements over 72 hours were compared between survivors
      and non-survivors, and medical and surgical patients were also compared. Our
      results showed that serum albumin decreased after ICU admission, most rapidly in
      the first 24 hours, in both survivors and non-survivors. Serum albumin was lower
      in non-survivors than in survivors, but albumin concentrations poorly
      differentiated the two groups. Medical patients had higher admission albumin
      levels than surgical patients, but both subgroups showed a similar albumin
      profile over 72 hours. We evaluated the prognostic value of serum albumin using
      receiver operator characteristic (ROC) curves. We constructed ROC curves for
      APACHE II score, admission albumin, albumin at 24 and 48 hours. We also combined
      APACHE II with albumin values and constructed the corresponding ROC curves. Our
      data showed that serum albumin had low sensitivity and specificity for predicting
      hospital mortality. Combining APACHE II score with serum albumin concentrations
      did not improve the accuracy of outcome prediction over that of APACHE II alone.

PMID- 12002930
TI  - Adhesive properties of Micropore, Transpore, Leucoplast and Sleek.
AB  - Adhesive tapes are a routine part of every anaesthetic. Until now there has been
      little clinical data on the efficacy of these tapes. This study compared
      Micropore Transpore, Leukoplast and Sleek to determine if any significant
      difference existed between the adhesive properties of these tapes. The tapes were
      trialled on bare skin, hairy skin, EMLA covered skin, skin with Benzoin Compound
      Tincture applied, and skin with Opsite spray applied. There was no significant
      difference in adhesiveness between Transpore, Leukoplast and Sleek, whilst
      Micropore was marginally inferior EMLA cream significantly decreased the adhesive
      properties of all tapes.

PMID- 12002931
TI  - The effect of a disposable probe cover on pulse oximetry.
AB  - The re-use of pulse oximeter probes presents the possibility of between-patient
      contamination. Use of a disposable polyethylene cover may reduce this risk. In a
      controlled, prospective study we examined the effect of such a cover on the
      accuracy of pulse oximetry. Each of ten volunteer subjects was monitored
      simultaneously by two identical Nellcor pulse oximeters, one with a plastic cover
      and the other, without a cover, used as a control. The pulse oximetry (SpO2)
      reading for each probe was recorded while subjects breathed 21% O2 and again
      while they breathed 10% O2. The probe cover was then swapped onto the other probe
      and the recordings were repeated. Ninety-five per cent limits of agreement in
      SpO2 (mean difference in SpO2 (1.95 x standard deviation of difference) between
      covered and non-covered probes were -0.6% to 0.6% while breathing 21% oxygen and 
      2.0% to 2.9% while breathing 10% oxygen. We conclude that a protective plastic
      sheath may induce a small error in pulse oximetry reading that is most marked
      during hypoxaemia. This error is unlikely to be of clinical significance.

PMID- 12002932
TI  - Atrial fibrillation, failed cardioversion, and electroconvulsive therapy.
AB  - A case is described in which an elderly male with atrial fibrillation and major
      depression underwent a course of electroconvulsive therapy. Two of the first
      three treatments were associated with other arrhythmias, during and after the
      procedure. Prior to the fourth treatment cardioversion was unsuccessful. During
      the fourth episode of electroconvulsive therapy, the patient reverted to sinus
      rhythm and remained in this rhythm. Reversion of atrial fibrillation to sinus
      rhythm may be associated with embolization if atrial thrombus has formed. Factors
      predisposing to changes in rhythm with electroconvulsive therapy and the
      management of patients with atrial fibrillation having electroconvulsive therapy
      are discussed.

PMID- 12002933
TI  - Cerebral protection with thiopentone during combined carotid endarterectomy and
      clipping of intracranial aneurysm.
AB  - We report a case of carotid endarterectomy and clipping of an ipsilateral
      internal carotid artery aneurysm in a patient with complete contralateral carotid
      stenosis. The patient developed an ischaemic electroencephalographic (EEG)
      tracing on temporary carotid clamping and bypass shunt was contraindicated. We
      used thiopentone titrated to EEG burst suppression for pharmacological cerebral
      protection during the subsequent prolonged carotid clamp necessary for carotid
      endarterectomy. We review the use of thiopentone for this purpose, in particular
      the evidence for efficacy, mechanism of action and optimal dosage and timing of
      administration.

PMID- 12002934
TI  - Prone position as a life-saving measure for acute pulmonary haemorrhage in a
      young adult with cystic fibrosis.
AB  - Fatal pulmonary haemorrhage is a rare complication of cystic fibrosis. A case of
      unexpected life-threatening pulmonary haemorrhage is presented, and the
      successful management of this problem including immediate prone ventilation.
      Different anaesthetic techniques, avoiding endotracheal intubation and positive
      pressure ventilation, which may avoid similar complications, are described.

PMID- 12002935
TI  - Acute autoimmune cardiomyopathy in primary antiphospholipid antibody syndrome.
AB  - We present a case of acute pulmonary oedema as the first presentation of
      autoimmune cardiomyopathy in primary antiphospholipid antibody syndrome in a
      patient who had no previous cardiac history. Five days of methylprednisolone at
      500 mg/day followed by 100 mg/day for 10 days and then a weaning course of oral
      prednisone resulted in effective resolution of the acute diffuse cardiomyopathy.
      Her cardiac status became clinically and echocardiographically normal. We
      illustrate the effectiveness of immunosuppressive therapy as an adjunct to
      standard anti-failure measures in such presentations and we outline the
      association between antiphospholipid antibodies and cardiac dysfunction.

PMID- 12002936
TI  - Haemorrhage of a thyroid cyst as an unusual complication of intubation.
AB  - A case is presented of haemorrhage into a thyroid cyst after endotracheal
      intubation for an elective nasal operation in a healthy young man. The
      haemorrhagic cyst compressed the trachea and the patient was taken to the
      intensive care unit with the endotracheal tube left in situ. Hemithyroidectomy
      was performed uneventfully two days later. Causes of haemorrhage into thyroid
      cysts are reviewed.

PMID- 12002937
TI  - Quinine ocular toxicity: treatment of blindness using therapy for vasospasm.
AB  - A case of ocular toxicity with vasospasm secondary to quinine poisoning is
      described. Therapy for vasospasm using nimodipine, hypertension, haemodilution
      and hypervolaemia was instituted with subsequent resolution of symptoms.

PMID- 12002938
TI  - Elective awake intubation in a patient with massive multinodular goitre
      presenting for radioiodine treatment.
AB  - We present the management of the potential airway complications in a case of
      massive multinodular goitre treated with radioactive iodine. The patient's
      trachea was prophylactically intubated, using a fibreoptic technique, to prevent
      further airway compromise due to thyroid oedema following radioactive iodine
      treatment. He remained awake and intubated for five days and was extubated when
      there was no clinical evidence of thyroid oedema as a consequence of his
      treatment. This approach avoided the considerable risk of thyroidectomy in a
      morbidly obese patient with airway obstruction. To the authors' knowledge this
      approach has not been previously described.

PMID- 12002939
TI  - Another knotted epidural catheter.
AB  - A lumbar epidural catheter inserted in a 24-year-old woman for labour analgesia,
      and subsequently used for post-caesarean epidural analgesia, proved difficult to
      remove. After multiple attempts, the entrapped catheter was dislodged intact,
      revealing a knot near its distal tip. Knotting of an epidural catheter leading to
      entrapment is a rare complication of epidural catheterization.

PMID- 12002940
TI  - ENT vs anaesthesia "straight" laryngoscopes.

PMID- 12002941
TI  - Ventilator-operator dyssynchrony?

PMID- 12002942
TI  - Differences in prevalence of seasonal affective disorder that are not explained
      by either genetic or latitude differences.
AB  - The prevalence of winter SAD was measured in two groups of a(lult Manitobans of
      wholly Icelandic (lescent, 210 resident in Winnipeg (50 degrees N) and 252
      resident in the nearby Interlake district (50.5 degrees N), using the Seasonal
      Pattern Assessment Questionnaire (SPAQ). These groups live practically at the
      same latitude and are according to all indications genetically identical. The age
      and-sex-standardized prevalence rates of winter SAD proved to be markedly higher
      in the Winnipeg population than in the Interlake population: 4.8% and 1.2%
      (p<0.001), respectively. This four-fold dif ference is evidently unexplained by
      genetic factors or a difference in latitude; its causes have yet to be
      discovered.

PMID- 12002943
TI  - Type 1 diabetes-related autoantibodies are rare in Alaska native populations.
AB  - OBJECTIVES: When clinical data were initially gathered from the Alaskan Eskimos
      in the 1950's, diabetes mellitus was noted to be quite rare. The prevalence of
      diabetes has increased significantly since that time, with rates of 10% reported
      recently in some Alaska native populations. Our goal was to understand the
      pathogenesis of diabetes among these groups, with the hypothesis that Alaskan
      Eskimos were predominantly affected by type 2 diabetes, not by latent autoimmune
      diabetes in adults (LADA). STUDY DESIGN: Population based case control study
      METHODS: We tested sera from subjects in two Eskimo villages for the presence of
      type 1 diabetes-related autoantibodies against glutamic acid decarboxylase
      (GAD65Ab) and tyrosine phosphatase-like islet antigen-2 (IA-2Ab). RESULTS: Among
      subjects from one Inupiat village (#1) and one SiberianYup'ik village (#2), there
      were 21 subjects with diabetes mellitus (DM), 17 with impaired glucose tolerance
      (IGT), and 226 healthy controls with normal glucose tolerance (NGT). In village
      1, GAD65 antibodies were not present in either diabetic subjects or those with
      IGT. One of the healthy controls (1%; 1/97) was positive for GAD65Ab. Similarly,
      no subjects from this village with DM or IGT had positive IA-2Ab titers, and one
      healthy control (1%; 1/97) was positive for IA-2Ab. In village 2, no DM subject
      was GAD65Ab positive. One (10%; 1/10) of the IGT subjects and two (1.6%;2/129) of
      the healthy controls were positive for GAD65Ab. In this village, two of the DM
      subjects (12%;2/17), one of the IGT subjects (10%; 1/10), and one of the healthy
      controls (0.8%;1/129) were IA-2Ab positive. No individual was positive for both
      GAD65Ab and IA-2Ab. CONCLUSION: Alaskan Inupiat and Siberian Yup'ik Eskimos
      appear to be predominantly affected by type 2 diabetes, not LADA.

PMID- 12002944
TI  - Circumpolar health cooperation and the International Union.

PMID- 12002945
TI  - Melatonin exhibits antioxidant properties in a mouse brain slice model of
      excitotoxicity.
AB  - OBJECTIVES: Stroke is a major cause of brain injury in Alaska. Since antioxidant
      levels are decreased in aged brain, the greater predisposition to neuronal death
      in stroke leading to subsequent neurodegeneration in aged individuals may be
      related to changes in oxidant balance. We studied the effect of the endogenous
      antioxidant melatonin on excitotoxic injury resulting from N-methyl-D-aspartate
      (NMDA)-induced damage by developing an organotypic mouse brain slice model. Our
      objective was to inhibit the effects of oxidative stress induced by NMDA in mouse
      brain slices, using melatonin. METHODS: An organotypic mouse brain slice culture
      was established at PO2 levels maintained between 80 - 100 mm Hg. NMDA, melatonin
      or both were added to the slices and antioxidant function was determined using
      the redox active iron assay as well as 8-OHG and HO-1 immunoassays. RESULTS: This
      slice system allows for better regulation of both NMDA and melatonin
      concentrations than can be achieved by in vivo studies. Supporting an antioxidant
      function, melatonin (100 microM) significantly decreased redox active iron, heme
      oxygenase (HO-1) induction and 8-hydroxyguanosine (8-OHG) following NMDA (50-100
      microM) insult. However, somewhat surprisingly, high concentrations of melatonin
      alone (1 mM), increased redox active iron levels and HO-1 induction. CONCLUSIONS:
      These results support the hypothesis that melatonin is a neuroprotective
      antioxidant. Our data also suggest that 1 mM melatonin may have detrimental
      effects.

PMID- 12002946
TI  - Neurobehavioral performance of Inuit children with increased prenatal exposure to
      methylmercury.
AB  - Exposure to methylmercury from marine mammals and other seafood may affect the
      development of the central nervous system. In a traditional Inuit community in
      Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have
      been examined in connection with all births. We examined 43 children at age 7-12
      years with a battery of neurobehavioral tests. The average mercury concentration
      in hair was 5.0 microg/g and 1.5 microg/g in children and mothers, respectively.
      Clinical neurological examination did not reveal any obvious deficits. However,
      neuropsychological tests showed possible exposure-associated deficits, though
      only in a few cases reaching statistical significance. In conjunction with data
      from other studies, peak latencies on brainstem auditory evoked potentials tended
      to be prolonged at increased exposure levels. The data from the present study
      therefore appears in accordance with other evidence that prenatal or early
      postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.

PMID- 12002947
TI  - Botulism among Alaska natives in the Bristol Bay area of southwest Alaska: a
      survey of knowledge, attitudes, and practices related to fermented foods known to
      cause botulism.
AB  - OBJECTIVES: Botulism cases due to traditional Alaska Native fermented foods occur
      periodically in Southwest Alaska. In this population, we conducted a survey on
      knowledge, attitudes, and practices related to botulism and fermented foods.
      METHODS: We interviewed 140 adults randomly chosen from nine villages. Data
      collected included fermented food consumption frequency; knowledge about the
      cause and symptoms of botulism; and fermented food preparation methods. RESULTS:
      Most respondents (81%) had eaten Alaska Native fermented foods at least once.
      Over 70% identified botulism as a foodborne illness, and over 87% believed eating
      certain Native fermented foods could cause botulism. One-third of fermented food
      preparers used plastic containers for fermentation. To prevent botulism, 45%
      vwould consider boiling fermented foods, and 65% would not eat foods fermented in
      plastic or glass containers. CONCLUSIONS: Despite high awareness of botulism in
      this population, one-third of fermented food preparers use plastic containers, a
      practice which may increase the risk of botulism. Misconceptions and acceptable
      prevention messages about botulism, such as using traditional nonplastic
      fermentation methods, were identified and included in an educational video.

PMID- 12002948
TI  - Psychiatric disorders of children and adolescents--a growing problem at school.
AB  - The purpose is to present the views of comprehensive school and senior secondary
      school teachers working in the Oulu province in Northern Finland concerning the
      behavioural and emotional disorders of their pupils, the actions taken by
      teachers to refer pupils for consultation, and the functionality of mental health
      services. The data were collected by questionnaires in 1998 and 2000. According
      to the teachers' estimates, the behavioural and emotional disorders of pupils
      have both increased in number and become more severe at all levels of primary and
      secondary education. The teachers of comprehensive schools and special schools
      mostly contacted the parents when a pupil was found to have psychiatric symptoms.
      At the early stages of referral the teachers often also consulted with the pupil
      welfare team for support. The teachers of senior secondary schools contacted
      primarily the school nurse and secondarily the parents. Teachers were content
      with the psychiatric health care services if their pupils benefited from them,
      but the availability of services and the flow of information were problems. It
      was also difficult to decide when to refer a pupil for consultation and
      treatment. The responsibilities and obligations for the availability and
      functionality of mental health services for children and adolescents were re
      defined and specified in a statute enforced as of January 2001. The question is
      how can we convert responsibilities and obligations into practical action?

PMID- 12002949
TI  - What do expressions with north and northern people tell us?
AB  - The aim of this article is to study linguistic expressions which include the
      words North and Northern people. This is done by philological and linguistic
      analysis of the material, which consists of different types of written documents
      dating from different historical periods. The oldest historical documents were
      produced by the Ancient Roman writers, who wrote about wild tribes living in the
      North. The expression "the evil from the North" in the Bible is also used by the
      Fathers of the Church, when describing the Great Migrations. The most recent
      material consists of academic texts-dealing with the Northern dimension--and
      everyday texts--in this case, mostly of bread packages--referring among other
      things to people's nutrition and health. Expressions referring to the North are
      also present in modern material, but the negative association of the older
      documents is not so present. All the texts, both historical and modern, are
      discussed as a whole from Finnish and Scandinavian points of view. Semiotic
      aspects are highlighted by the use of some visual illustrations from the
      different texts in point.

PMID- 12002950
TI  - Substance versus style: a new look at social desirability in motivating contexts.
AB  - Although there is an emerging consensus that social desirability does not
      meaningfully affect criterion-related validity, several researchers have
      reaffirmed the argument that social desirability degrades the construct validity
      of personality measures. Yet, most research demonstrating the adverse
      consequences of faking for construct validity uses a fake-good instruction set.
      The consequence of such a manipulation is to exacerbate the effects of response
      distortion beyond what would be expected under realistic circumstances (e.g., an
      applicant setting). The research reported in this article was designed to assess
      these issues by using real-world contexts not influenced by artificial
      instructions. Results suggest that response distortion has little impact on the
      construct validity of personality measures used in selection contexts.

PMID- 12002951
TI  - Climate strength: a new direction for climate research.
AB  - Climate strength was conceptualized within D. Chan's (1998) discussion of
      compositional models and the concept of culture strength from the organizational
      culture literature. Climate strength was operationalized in terms of within-group
      variability in climate perceptions-the less within-group variability, the
      stronger the climate. The authors studied climate strength in the context of
      research linking employee service climate perceptions to customer satisfaction.
      The hypothesis was tested that climate strength moderates the relationship
      between employee perceptions of service climate and customer satisfaction
      experiences. Partial support for the hypothesis was reported in both a concurrent
      and predictive (3-year) test across 118 branches of a bank. In the predictive
      study only the interaction of climate and climate strength predicted customer
      satisfaction. Implications for future research on climate and climate strength
      are discussed.

PMID- 12002952
TI  - The (un)reasonableness of reporting: antecedents and consequences of reporting
      sexual harassment.
AB  - This study places the reporting of sexual harassment within an integrated model
      of the sexual harassment process. Two structural models were developed and tested
      in a sample (N = 6,417) of male and female military personnel. The 1st model
      identifies determinants and effects of reporting; reporting did not improve--and
      at times worsened--job, psychological, and health outcomes. The authors argue
      that organizational responses to reports (i.e., organizational remedies,
      organizational minimization, and retaliation) as well as procedural satisfaction
      can account for these negative effects. The 2nd model examines these mediating
      mechanisms; results suggest that these mediators, and not reporting itself, are
      the source of the negative effects of reporting. Organizational and legal
      implications of these findings are discussed.

PMID- 12002953
TI  - Retaking ability tests in a selection setting: implications for practice effects,
      training performance, and turnover.
AB  - This field study investigated the effect of retaking identical selection tests on
      subsequent test scores of 4,726 candidates for law enforcement positions. For
      both cognitive ability and oral communication ability selection tests, candidates
      produced significant score increases between the 1st and 2nd and the 2nd and 3rd
      test administrations. Furthermore, the repeat testing relationships with posthire
      training performance and turnover were examined in a sample of 1,515 candidates
      eventually selected into the organization. As predicted from persistence and
      continuance commitment rationales, the number of tests necessary to gain entry
      into the organization was positively associated with training performance and
      negatively associated with turnover probability.

PMID- 12002954
TI  - Relationship quality and relationship context as antecedents of person- and task
      focused interpersonal citizenship behavior.
AB  - A model hypothesizing relationship quality and relationship context as
      antecedents of two complementary forms of interpersonal citizenship behavior
      (ICB) was tested. Measures with coworkers as the frame of reference were used to
      collect data from 273 individuals working in 2 service-oriented organizations. As
      hypothesized, variables reflecting relationship quality were associated with
      person-focused ICB, as mediated by empathic concern. Also as hypothesized, a
      relationship context variable, network centrality, exhibited a direct
      relationship with task-focused ICB. Unexpectedly, network centrality was directly
      associated with person-focused ICB. and empathic concern was associated with task
      focused ICB. The results are discussed, and implications for research and
      practice are offered.

PMID- 12002955
TI  - Business-unit-level relationship between employee satisfaction, employee
      engagement, and business outcomes: a meta-analysis.
AB  - Based on 7,939 business units in 36 companies, this study used meta-analysis to
      examine the relationship at the business-unit level between employee satisfaction
      engagement and the business-unit outcomes of customer satisfaction, productivity,
      profit, employee turnover, and accidents. Generalizable relationships large
      enough to have substantial practical value were found between unit-level employee
      satisfaction-engagement and these business-unit outcomes. One implication is that
      changes in management practices that increase employee satisfaction may increase
      business-unit outcomes, including profit.

PMID- 12002956
TI  - Gender-related biases in evaluations of sex discrimination allegations: is
      perceived threat the key?
AB  - Hypotheses derived from defensive attribution theory and social identity theory
      were tested in 3 laboratory experiments examining the effects of plaintiff and
      observer gender on perceived threat, plaintiff identification, and sex
      discrimination. In Study 1, women differentiated plaintiffs on the basis of
      gender, whereas men did not. Study 2 showed that this bias occurred because
      employment discrimination was personally threatening to women but not to men. In
      Study 3, the bias was reversed in a child custody context. As predicted, men
      found this context to be significantly more threatening than did women and
      subsequently exhibited a similarity bias. Mediation analyses suggested that
      responsibility attributions explained most of the variance in discrimination
      judgments associated with the plaintiff gender by observer gender interactions.

PMID- 12002957
TI  - Note-taking in the employment interview: effects on recall and judgments.
AB  - Although note-taking in the employment interview is highly recommended, little
      research has examined its effects. This study investigated the effects of note
      taking styles, review of the notes, and content of the notes on participants'
      cued recall of information and decisions made from videotaped employment
      interviews. Note-taking increased recall accuracy but not judgment accuracy.
      Being able to review notes resulted in increased judgment accuracy for those
      taking conventional-style notes. The content of the notes also had important
      implications for conventional note-takers, suggesting some benefits of recording
      notes using the key-points style. The findings suggest that the act of note
      taking may be more important for memory and legal reasons than for improving the
      decisions made by interviewers.

PMID- 12002958
TI  - Transformational leadership and moral reasoning.
AB  - Terms such as moral and ethical leadership are used widely in theory, yet little
      systematic research has related a sociomoral dimension to leadership in
      organizations. This study investigated whether managers' moral reasoning (n =
      132) was associated with the transformational and transactional leadership
      behaviors they exhibited as perceived by their subordinates (n = 407). Managers
      completed the Defining Issues Test (J. R. Rest, 1990), whereas their subordinates
      completed the Multifactor Leadership Questionnaire (B. M. Bass & B. J. Avolio,
      1995). Analysis of covariance indicated that managers scoring in the highest
      group of the moral-reasoning distribution exhibited more transformational
      leadership behaviors than leaders scoring in the lowest group. As expected, there
      was no relationship between moral-reasoning group and transactional leadership
      behaviors. Implications for leadership development are discussed.

PMID- 12002959
TI  - Trust in the face of conflict: the role of managerial trustworthy behavior and
      organizational context.
AB  - The authors explored the role of attributions in shaping employees' trust in
      their managers in the context of negative events. The authors examined how 2
      forms of managerial trustworthy behavior (open communication and demonstrating
      concern for employees) and organizational policies relate to attributions, trust
      in the manager, and organizational citizenship behavior. Participants were 115
      credit union employees who responded to a critical incident regarding a
      disagreement with their managers. As hypothesized, trustworthy behavior was
      negatively related to attributions of personal responsibility for negative
      encounters, and this relationship was stronger when human resource policies were
      perceived as unfair. Managerial trustworthy behavior was also positively related
      to trust in the manager and organizational citizenship behavior. Personal
      attributions partially mediated the relationship between trustworthy behavior and
      trust.

PMID- 12002960
TI  - Computer-adaptive testing: the impact of test characteristics on perceived
      performance and test takers' reactions.
AB  - This study examined how specific features of adaptive tests are related to test
      takers' reactions. Participants took a computer-adaptive test in which 2
      features, difficulty of the initial item and difficulty of subsequent items, were
      manipulated, then responded to questionnaires assessing their reactions to the
      test. The data show that the relationship between a test's objective difficulty,
      which was determined by the 2 manipulated test characteristics, and reactions was
      fully mediated by perceived performance. Additional analyses evaluated the impact
      of feedback on reactions to the adaptive test. In general, feedback that was
      consistent with perceptions of performance was positively related to reactions.
      The results suggest that minor changes to the design of an adaptive test may
      potentially enhance examinees' reactions.

PMID- 12002961
TI  - Black applicants' reactions to affirmative action plans: effects of plan content
      and previous experience with discrimination.
AB  - This study examined the effects of plan content and previous experience with
      discrimination on Black respondents' reactions to affirmative action plans. Black
      engineering students (N = 1,173) were randomly assigned to 1 of 6 plans
      implemented by a hypothetical organization and were asked to provide ratings of
      perceived fairness and intention to pursue a position at the organization. There
      were significant effects of plan content on perceived faimess and job pursuit
      intentions. Perceived fairness mediated the effect of content on intentions.
      Furthermore, previous experience with discrimination interacted with content to
      affect intentions. Individuals who had experienced relatively more discrimination
      in the workplace reported stronger intentions to pursue a position at an
      organization whose plan specified special training opportunities for minorities.

PMID- 12002962
TI  - The moderating influence of job performance dimensions on convergence of
      supervisory and peer ratings of job performance: unconfounding construct-level
      convergence and rating difficulty.
AB  - Meta-analysis was used to cumulate the correlations between supervisor and peer
      ratings for different dimensions of job performance. The general pattern in the
      data suggested that raters from the same organizational level disagree as much as
      raters from different levels. Methods were used to separate the effects of rating
      difficulty and lack of construct-level convergence on the correlation between
      supervisor and peer ratings. The authors found complete construct-level
      convergence for ratings of overall job performance, productivity, effort, job
      knowledge, quality, and leadership but not for ratings of administrative
      competence, interpersonal competence, and compliance or acceptance of authority.
      Higher rating difficulty was more strongly associated with lower mean observed
      peer-supervisor correlations than were construct-level disagreements between
      peers and supervisors. Implications for research and practice are discussed.

PMID- 12002963
TI  - Substantive and operational issues of response bias across levels of analysis: an
      example of climate-satisfaction relationships.
AB  - Two studies tested whether method variance is present at multiple levels of
      analysis and whether methodological procedures can minimize its impact. In Study
      1, 8,052 employees from 71 hotels completed measures of climate, work environment
      characteristics, and satisfaction. A comparison of correlations at the individual
      level, cross-level, cross-level split, aggregate level, and aggregate-split level
      of analysis revealed that response bias was present across multiple levels.
      Results suggest that samples should be split in half when cross-level and
      aggregate correlations are computed to ameliorate response bias problems that
      arise from individual-level method variance. In Study 2, results indicated that
      the temporal spacing of measures of climate and satisfaction influenced response
      bias. Implications and recommendations for future research are discussed.

PMID- 12002964
TI  - Comparison of two random-effects methods of meta-analysis.
AB  - Two studies compared the Schmidt-Hunter method of meta-analysis (J. E. Hunter &
      F. L. Schmidt, 1990) with the method described by L. V. Hedges and J. L. Vevea
      (1998). Study 1 evaluated estimates of rho, sigmarho, and resulting credibility
      intervals for both models through Monte Carlo methods. Results showed slight
      differences between the 2 methods. In Study 2, a reanalysis of published meta
      analyses using both methods with several artifact distributions showed that
      although both choice of technique and type of correction could matter, the
      technique of meta-analysis used is less influential on the study outcome than is
      the choice of artifact correction.

PMID- 12002965
TI  - Self-monitoring personality at work: a meta-analytic investigation of construct
      validity.
AB  - The validity of self-monitoring personality in organizational settings was
      examined. Meta-analyses were conducted (136 samples; total N = 23,191)
      investigating the relationship between self-monitoring personality and work
      related variables, as well as the reliability of various self-monitoring
      measures. Results suggest that self-monitoring has relevance for understanding
      many organizational concerns, including job performance and leadership emergence.
      Sample-weighted mean differences favoring male respondents were also noted,
      suggesting that the sex-related effects for self-monitoring may partially explain
      noted disparities between men and women at higher organizational levels (i.e.,
      the glass ceiling). Theory building and additional research are needed to better
      understand the construct-related inferences about self-monitoring personality,
      especially in terms of the performance, leadership, and attitudes of those at top
      organizational levels.

PMID- 12002966
TI  - Computer-assisted communication and team decision-making performance: the
      moderating effect of openness to experience.
AB  - This study examined the effects of computer-assisted communication on team
      decision-making performance as a function of the team's openness to experience.
      Seventy-nine teams performing a multiple-cue probability learning task were
      randomly assigned to 1 of 2 experimental conditions: (a) verbal communication or
      (b) computer-assisted communication (which combined verbal and computerized
      communication). The results indicated that access to computer-assisted
      communication improved the decision-making performance of teams, but only when
      the teams were high in openness to experience. This effect was observed using
      both global openness and more specific openness facets, as well as a variety of
      team-level aggregation strategies. Moreover, the beneficial effects of openness
      in computer-assisted conditions were mediated by the efficiency with which teams
      integrated verbal and computerized forms of communication.

PMID- 12002967
TI  - Effects of perceived disability on persuasiveness of computer-synthesized speech.
AB  - Are perceptions of computer-synthesized speech altered by the belief that the
      person using this technology is disabled? In a 2 x 2 factorial design,
      participants completed an attitude pretest and were randomly assigned to watch an
      actor deliver a persuasive appeal under 1 of the following 4 conditions: disabled
      or nondisabled using normal speech and disabled or nondisabled using computer
      synthesized speech. Participants then completed a posttest survey and a series of
      questionnaires assessing perceptions of voice, speaker, and message. Natural
      speech was perceived more favorably and was more persuasive than computer
      synthesized speech. When the speaker was perceived to be speech-disabled,
      however, this difference diminished. This finding suggests that negatively viewed
      assistive technologies will be perceived more favorably when used by people with
      disabilities.

PMID- 12002968
TI  - The environments of stem cells--biology, ethics and policy.

PMID- 12002969
TI  - Headaches due to arachnoid leak.

PMID- 12002970
TI  - Telehealth a medicolegal quagmire?

PMID- 12002971
TI  - Orwellian paranoia in the neonatal ICU.

PMID- 12002972
TI  - Saskatchewan continues breast cancer screening.

PMID- 12002973
TI  - Smallpox still poses a threat.

PMID- 12002974
TI  - Measles vaccine dosage.

PMID- 12002975
TI  - Revisiting the modern scientific physician.

PMID- 12002976
TI  - Revisiting the modern scientific physician.

PMID- 12002977
TI  - Clinical practice guidelines for the care and treatment of breast cancer: 14. The
      role of hormone replacement therapy in women with a previous diagnosis of breast
      cancer.
AB  - OBJECTIVE: To provide information and recommendations to women with a previous
      diagnosis of breast cancer and their physicians regarding hormone replacement
      therapy (HRT). OUTCOMES: Control of menopausal symptoms, quality of life,
      prevention of osteoporosis, prevention of cardiovascular disease, risk of
      recurrence of breast cancer, risk of death from breast cancer. EVIDENCE:
      Systematic review of English-language literature published from January 1990 to
      July 2001 retrieved from MEDLINE and CANCERLIT. RECOMMENDATIONS: * Routine use of
      HRT (either estrogen alone or estrogen plus progesterone) is not recommended for
      women who have had breast cancer. Randomized controlled trials are required to
      guide recommendations for this group of women. Women who have had breast cancer
      are at risk of recurrence and contralateral breast cancer. The potential effect
      of HRT on these outcomes in women with breast cancer has not been determined in
      methodologically sound studies. However, in animal and in vitro studies, the
      development and growth of breast cancer is known to be estrogen dependent. Given
      the demonstrated increased risk of breast cancer associated with HRT in women
      without a diagnosis of breast cancer, it is possible that the risk of recurrence
      and contralateral breast cancer associated with HRT in women with breast cancer
      could be of a similar magnitude. * Postmenopausal women with a previous diagnosis
      of breast cancer who request HRT should be encouraged to consider alternatives to
      HRT. If menopausal symptoms are particularly troublesome and do not respond to
      alternative approaches, a well-informed woman may choose to use HRT to control
      these symptoms after discussing the risks with her physician. In these
      circumstances, both the dose and the duration of treatment should be minimized.
      VALIDATION: Internal validation within the Steering Committee on Clinical
      Practice Guidelines for the Care and Treatment of Breast Cancer; no external
      validation. SPONSOR: The steering committee was convened by Health Canada.
      COMPLETION DATE: October 2001.

PMID- 12002978
TI  - Effects of rising tuition fees on medical school class composition and financial
      outlook.
AB  - BACKGROUND: Since 1997, tuition has more than doubled at Ontario medical schools
      but has remained relatively stable in other Canadian provinces. We sought to
      determine whether the increasing tuition fees in Ontario affected the demographic
      characteristics and financial outlook of medical students in that province as
      compared with those of medical students in the rest of Canada. METHODS: As part
      of a larger Internet survey of all students at Canadian medical schools outside
      Quebec, conducted in January and February 2001, we compared the respondents from
      Ontario schools with those from the other schools (control group). Respondents
      were asked about their age, sex, self-reported family income (as a direct
      indicator of socioeconomic status), the first 3 digits of their postal code at
      graduation from high school (as an indirect indicator of socioeconomic status),
      and importance of financial considerations in choosing a specialty and location
      of practice. We used logistic regression models to see if temporal changes (1997
      v. 2000) among Ontario medical students differed from those among medical
      students elsewhere in Canada apart from Quebec. RESULTS: Responses were obtained
      from 2994 (68.5%) of 4368 medical students. Across the medical schools, there was
      an increase in self-reported family income between 1997 and 2000 (p = 0.03). In
      Ontario, the proportion of respondents with a family income of less than $40,000
      declined from 22.6% to 15.0%. However, compared with the control respondents, the
      overall rise in family income among Ontario students was not statistically
      significant. First-year Ontario students reported higher levels of expected debt
      at graduation than did graduating students (median $80,000 v. $57,000) (p <
      0.001), and the proportion of students expecting to graduate with debt of at
      least $100,000 more than doubled. Neither of these differences was observed in
      the control group. First-year Ontario students were also more likely than fourth
      year Ontario students to report that their financial situation was "very" or
      "extremely" stressful and to cite financial considerations as having a major
      influence on specialty choice or practice location. These differences were not
      observed in the control group. INTERPRETATION: At Canadian medical schools, there
      are fewer students from low-income families in general. However, Ontario medical
      students report a large increase in expected debt on graduation, an increased
      consideration of finances in deciding what or where to practise, and increasing
      financial stress, factors that are not observed among students in other
      provinces.

PMID- 12002979
TI  - Characteristics of first-year students in Canadian medical schools.
AB  - BACKGROUND: The demographic and socioeconomic profile of medical school classes
      has implications for where people choose to practise and whether they choose to
      treat certain disadvantaged groups. We aimed to describe the demographic and
      socioeconomic characteristics of first-year Canadian medical students and compare
      them with those of the Canadian population to determine whether there are groups
      that are over- or underrepresented. Furthermore, we wished to test the hypothesis
      that medical students often come from privileged socioeconomic backgrounds.
      METHODS: As part of a larger Internet survey of all students at Canadian medical
      schools outside Quebec, conducted in January and February 2001, first-year
      students were asked to give their age, sex, self-described ethnic background
      using Statistics Canada census descriptions and educational background. Postal
      code at the time of high school graduation served as a proxy for socioeconomic
      status. Respondents were also asked for estimates of parental income and
      education. Responses were compared when possible with Canadian age-group-matched
      data from the 1996 census. RESULTS: Responses were obtained from 981 (80.2%) of
      1223 first-year medical students. There were similar numbers of male and female
      students (51.1% female), with 65% aged 20 to 24 years. Although there were more
      people from visible minorities in medical school than in the Canadian population
      (32.4% v. 20.0%) (p < 0.001), certain minority groups (black and Aboriginal) were
      underrepresented, and others (Chinese, South Asian) were overrepresented. Medical
      students were less likely than the Canadian population to come from rural areas
      (10.8% v. 22.4%) (p< 0.001) and were more likely to have higher socioeconomic
      status, as measured by parents' education (39.0% of fathers and 19.4% of mothers
      had a master's or doctoral degree, as compared with 6.6% and 3.0% respectively of
      the Canadian population aged 45 to 64), parents' occupation (69.3% of fathers and
      48.7% of mothers were professionals or high-level managers, as compared with
      12.0% of Canadians) and household income (15.4% of parents had annual household
      incomes less than $40,000, as compared with 39.7% of Canadian households; 17.0%
      of parents had household incomes greater than $160,000, as compared with 2.7% of
      Canadian households with an income greater than $150,000). Almost half (43.5%) of
      the medical students came from neighbourhoods with median family incomes in the
      top quintile (p < 0.001). A total of 57.7% of the respondents had completed 4
      years or less of postsecondary studies before medical school, and 29.3% had
      completed 6 or more years. The parents of the medical students tended to have
      occupations with higher social standing than did working adult Canadians; a total
      of 15.6% of the respondents had a physician parent. INTERPRETATION: Canadian
      medical students differ significantly from the general population, particularly
      with regard to ethnic background and socioeconomic status.

PMID- 12002980
TI  - The Canadian obesity epidemic, 1985-1998.

PMID- 12002981
TI  - Identifying and managing adverse environmental health effects: a new series.

PMID- 12002982
TI  - High society.

PMID- 12002983
TI  - Identifying and managing adverse environmental health effects: 1. Taking an
      exposure history.
AB  - Public concern and awareness are growing about adverse health effects of exposure
      to environmental contaminants. Frequently patients present to their physicians
      with questions or concerns about exposures to such substances as lead, air
      pollutants and pesticides. Most primary care physicians lack training in and
      knowledge of the clinical recognition, management and avoidance of such
      exposures. We have found that it can be helpful to use the CH2OPD2 mnemonic
      (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) as a tool
      to identify a patient's history of exposures to potentially toxic environmental
      contaminants. In this article we discuss why it is important to take a patient's
      environmental exposure history, when and how to take the history, and how to
      interpret the findings. Possible routes of exposure and common sources of
      potentially toxic biological, physical and chemical substances are identified. A
      case of sick-building syndrome is used to illustrate the use of the mnemonic.

PMID- 12002984
TI  - The hyponatremic patient: a systematic approach to laboratory diagnosis.
AB  - Hyponatremia (serum sodium level less than 134 mmol/L) is a common electrolyte
      disturbance. Its high prevalence and potential neurologic sequelae make a logical
      and rigorous differential diagnosis mandatory before any therapeutic
      intervention. A history of concurrent illness and medication use as well as the
      assessment of extracellular volume status on physical examination may provide
      useful clues as to the pathogenesis of hyponatremia. Measurement of the effective
      serum tonicity (serum osmolality less serum urea level) is the first step in the
      laboratory evaluation. In patients with normal or elevated effective serum
      osmolality (280 mOsm/kg or greater), pseudohyponatremia should be excluded. In
      the hypo-osmolar state (serum osmolality less than 280 mOsm/kg), urine osmolality
      is used to determine whether water excretion is normal or impaired. A urine
      osmolality value of less than 100 mOsm/kg indicates complete and appropriate
      suppression of antidiuretic hormone secretion. A urine sodium level less than 20
      mmol/L is indicative of hypovolemia, whereas a level greater than 40 mmol/L is
      suggestive of the syndrome of inappropriate antidiuretic hormone secretion.
      Levels of hormones (thyroid-stimulating hormone and cortisol) and arterial blood
      gases should be determined in difficult cases of hyponatremia.

PMID- 12002985
TI  - Meningococcal disease: oh no, not another childhood vaccine.

PMID- 12002986
TI  - HIV drug stavudine (Zerit, d4T) and symptoms mimicking Guillain-Barre syndrome.

PMID- 12002987
TI  - Onychomadesis and Kawasaki disease.

PMID- 12002988
TI  - Why is Ottawa so scared of the stem cell?

PMID- 12002989
TI  - Stem cell research: "with no law, the situation is very permissive".

PMID- 12002990
TI  - The doctor isn't in.

PMID- 12002991
TI  - Poor economy means poorest Americans face health care cuts.

PMID- 12002992
TI  - CJ-21,164, a new D-glucose-6-phosphate phosphohydrolase inhibitor produced by a
      fungus Chloridium sp.
AB  - A new D-glucose-6-phosphate phosphohydrolase (G6Pase) inhibitor, CJ-21,164 (1)
      was isolated from the fermentation broth of the fungus Chloridium sp. CL48903.
      The structure was elucidated to be a novel tetramer of the salicylic acid
      derivatives by spectroscopic analyses. Compound I inhibited G6Pase in rat liver
      microsomes with an IC50 of 1.6 microM. Glucose output from hepatocytes isolated
      from rat liver was inhibited when I was present in the incubation medium,
      consistent with the role of I as a G6Pase inhibitor.

PMID- 12002993
TI  - Kosinostatin, a quinocycline antibiotic with antitumor activity from
      Micromonospora sp. TP-A0468.
AB  - Kosinostatin, a quinocycline antibiotic was isolated from the culture broth of an
      actinomycete strain TP-A0468 along with isoquinocycline B. The producing strain
      was isolated from the seawater sample collected in Toyama Bay and identified as
      Micromonospora sp. based on the taxonomic study. Kosinostatin was obtained from
      the culture fluid by solvent extraction and ODS column chromatography.
      Kosinostatin inhibited the growth of Gram-positive bacteria strongly (MIC=0.039
      microg/ml) and Gram-negative bacteria and yeasts moderately (MIC= 1.56
      approximately 12.5 microg/ml). It showed cytotoxicity against various cancer cell
      lines with the IC50 of 0.02 approximately 0.6 microm and inhibited human DNA
      topoisomerase Ila with the IC50 of 3 approximately 10 microM.

PMID- 12002994
TI  - NMR analysis of quinocycline antibiotics: structure determination of
      kosinostatin, an antitumor substance from Micromonospora sp. TP-A0468.
AB  - A quinocycline antibiotic, kosinostatin, was isolated from the culture broth of
      Micromonospora sp. TP-A0468 along with isoquinocycline B. Structure of
      kosinostatin was determined to be the stereoisomer of isoquinocycline B regarding
      to the stereochemistry at the C-2' spiro carbon by NMR analysis. Kosinostatin
      isomerizes to isoquinocycline B through the inversion of the stereocenter at C
      2'. Comparison of physico-chemical properties indicated that kosinostatin is
      presumably identical with quinocycline B isolated by CELMER et al. from
      Streptomyces aureofaciens.

PMID- 12002995
TI  - Migrastatin and a new compound, isomigrastatin, from Streptomyces platensis.
AB  - Streptomyces platensis (strain NRRL 18993), a producer of dorrigocins, was shown
      to produce migrastatin, a cyclic congener of dorrigocin A previously reported
      from a different organism. Additionally a new compound isomeric to migrastatin,
      isomigrastatin, was also isolated and its structure was determined to be a cyclic
      form of dorrigocin B. Both compounds were fully characterized from MS and NMR
      data. Product titers of both were improved by the addition of XAD-16 resin to the
      fermentation medium.

PMID- 12002996
TI  - Absolute stereostructures of cell adhesion inhibitors, macrosphelides H and L,
      from Periconia byssoides OUPS-N133.
AB  - Macrosphelide L has been isolated from a strain of Periconia byssoides originally
      separated from the sea hare Aplysia kurodai, and the absolute stereostructures of
      this material and macrosphelide H, previously undetermined, have been elucidated
      on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some
      chemical transformation. (R)-Methyl 3-p-bromobenzoyloxy-5-oxohexanoate has been
      synthesized for configurational assignments of macrosphelide H. These
      macrosphelides inhibited the adhesion of human-leukemia HL-60 cells to HUVEC.

PMID- 12002997
TI  - Stachyflin and acetylstachyflin, novel anti-influenza A virus substances,
      produced by Stachybotrys sp. RF-7260. I. Isolation, structure elucidation and
      biological activities.
AB  - Two novel compounds, stachyflin and acetylstachyflin, have been isolated by solid
      state fermentation of Stachybotrys sp. RF-7260. The structures of both
      metabolites, determined by detailed NMR analyses and X-ray crystallographic
      analysis, are novel with a pentacyclic moiety including cis-fused decalin. The
      absolute stereochemistry of stachyflins was determined by circular dichroism
      analysis. Stachyflin showed antiviral activity against influenza A virus (H1N1)
      in vitro with an IC50 value of 0.003 microM. Acetylstachyflin was about 77-fold
      less active than stachyflin.

PMID- 12002998
TI  - Stachyflin and acetylstachyflin, novel anti-influenza A virus substances,
      produced by Stachybotrys sp. RF-7260. II. Synthesis and preliminary structure
      activity relationships of stachyflin derivatives.
AB  - Stachyflin and acetylstachyflin, produced by Stachybotrys sp. RF-7260, were found
      to have potent anti-influenza A virus activity. Stachyflin is a new class of
      hemagglutinin fusion inhibitors of influenza A virus. Several derivatives were
      synthesized from acetylstachyflin and subjected to preliminary examination of
      their structure-activity relationships. Among them, the 3-oxo and 3,8'-dioxo
      derivatives showed potent antiviral activity similar to stachyflin. The 3-epi
      derivative was four times less active than stachyflin. Modification of the 6'
      hydroxy group and the C-5' position markedly diminished the antiviral activity.

PMID- 12002999
TI  - Funicone-related compounds, potentiators of antifungal miconazole activity,
      produced by Talaromycesflavus FKI-0076.
AB  - Talaromyces flavus FKI-0076, a soil isolate, was found to produce compounds which
      reinforce the anti-Candida albicans activity of miconazole. Four structurally
      related compounds, a novel one, designated actofunicone, and the knowns
      deoxyfunicone, vermistatin and NG-012, were isolated from the culture broth by
      solvent extraction, ODS column chromatography and HPLC. The structure of
      actofunicone was elucidated as benzoic acid, 3,5-dimethoxy-2-[[4-oxo-6-(2
      acetyloxy propyl)-4H-pyran-3-yl]carbonyl]-, methyl ester by various spectroscopic
      analyses including NMR experiments. These compounds potentiated the anti-C.
      albicans activity of miconazole, decreasing the IC50 value of miconazole from 19
      microM to 1.6 approximately 3.7 microM in the presence of the funicones.

PMID- 12003000
TI  - Preparation and cytotoxic activity of some new rhodomycin derivatives bearing
      modifications in the sugar moiety.
AB  - The synthesis and structural determination of a number of new rhodomycin
      derivatives, modified in the sugar part are described. The cytotoxicity against
      leukemic L1210 cells of these compounds is reported, along with beta
      rhodomycinone and two regioisomers of the above compounds, which were isolated
      during the synthetic procedure.

PMID- 12003001
TI  - Total synthesis of novel antibiotics pyloricidin A, B and C and their application
      in the study of pyloricidin derivatives.
AB  - The novel natural antibiotics pyloricidin A, B and C, which possess potent and
      highly selective anti-Helicobacter pylori activity, were synthesized from D
      galactosamine as a chiral template for the common (2S,3R,4R,5S)-5-amino-2,3,4,6
      tetrahydroxyhexanoic acid moiety. The synthetic strategy, using 2-amino-2
      deoxyuronic acid derivatives as key intermediates, was also useful to prepare a
      series of derivatives modified at the beta-D-phenylalanine and with altered
      stereochemistry on the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. From the
      drastic decrease of their anti-H. pylori activity, it was clear that the beta-D
      phenylalanine part and the stereochemistry of the 5-amino-2,3,4,6
      tetrahydroxyhexanoic acid moiety were significant for the activity.

PMID- 12003002
TI  - Trienomycin G, a new inhibitor of nitric oxide production in microglia cells,
      from Streptomyces sp. 91614.

PMID- 12003003
TI  - Sterins A and B, new antioxidative compounds from Stereum hirsutum.

PMID- 12003004
TI  - Phenylpyropene C, a new inhibitor of acyl-CoA: cholesterol acyltransferase
      produced by Penicillium griseofulvum F1959.

PMID- 12003005
TI  - Structure of sch 419560, a novel alpha-pyrone antibiotic produced by Pseudomonas
      fluorescens.

PMID- 12003006
TI  - Antifungal mechanism of FK463 against Candida albicans and Aspergillus fumigatus.

PMID- 12003007
TI  - Production of selenohomocystine as an antibiotic by a marine Bacillus sp. no. 14
      with selenomethionine resistance.

PMID- 12003008
TI  - Learning about hepatitis C infection.

PMID- 12003009
TI  - The truth about low-carb, high-protein diets.

PMID- 12003010
TI  - Lauriston S. Taylor Lecture: Assuring the safety of medical diagnostic
      ultrasound.
AB  - In 1980, the NCRP formed Scientific Committee 66 with an assignment to address
      the subject of "biological effects of ultrasound and exposure criteria." It was
      recognized that the primary source of exposure to ultrasound was through medical
      applications and, especially, through procedures employing diagnostic ultrasound.
      While the risk to patients from these procedures was believed small, it was
      considered important for users to understand it, in view of the widespread use of
      diagnostic ultrasound. In proceeding with this assignment, much emphasis has been
      given to the mechanisms by which ultrasound can bring about changes in biological
      structures or processes. Thermal effects are possible; the local temperature can
      rise especially rapidly where ultrasound impinges on bone. From theory for heat
      production and transport, and by analysis of experimental results with mammals,
      information has been obtained for guiding users in avoiding harm from temperature
      elevation. Nonthermal effects, such as capillary rupture, can occur when
      ultrasound is incident on tissue that normally contains gas-filled cavities, as
      in adult lung or intestine, or on any tissue containing gaseous contrast agents.
      Theory from fluid dynamics, together with experimental findings, has led to
      quantitative guidance for avoiding damage from acoustically activated cavities.
      It is felt that good practice in applying diagnostic ultrasound is best assured
      by making it possible for users to be well informed on safety matters so that
      they can feel justifiably confident in making appropriate choices of operating
      conditions. A promising and useful approach is in the display of safety
      information on the diagnostic ultrasound screen, which is now a feature of United
      States standards.

PMID- 12003011
TI  - Historical overview of atmospheric nuclear weapons testing and estimates of
      fallout in the continental United States.
AB  - From 1945 to 1980, over 500 weapons tests were conducted in the atmosphere at a
      number of locations around the world. These tests resulted in the release of
      substantial quantities of radioactive debris to the environment. Local,
      intermediate, and global fallout deposition densities downwind from test sites
      depended on the heights of bursts, the yields, and the half-lives and
      volatilities of the particular fission or activation products, as well as on the
      meteorological conditions. A number of national and international monitoring
      programs were established to trace the fallout through the atmosphere and
      biosphere. These programs included continuous monitoring of ground-level air,
      exposure rates, and deposition as well as periodic sampling of food, bone, water,
      soil, and stratospheric air. Although data for specific high-yield tests are
      still classified, the fission and fusion yields of the various tests and test
      series have been estimated and from this information the quantities of specific
      fission and activation products released into the atmosphere have been
      determined. The geographic and temporal variations in the fallout deposition of
      specific radionuclides based on both actual measurements and model calculations
      are discussed in this paper. A feasibility study to estimate the deposition
      density (deposition per unit area) of particular radionuclides from both Nevada
      Test Site and "global" fallout on a county-by-county scale for the continental
      United States is described. These deposition estimates provide a basis for
      reconstructing population exposure and dose. They support the feasibility of a
      more detailed evaluation of the population doses that resulted from fallout from
      atmospheric tests to document the experience fully and to report results more
      systematically and completely to the world community. The impact of weapons
      fallout will continue to be felt for years to come since a contaminant baseline
      has been imposed on the ambient radiation environment that will be an important
      factor in the assessment of past and future releases of radioactive materials
      into the biosphere.

PMID- 12003012
TI  - The development of field-based measurement methods for radioactive fallout
      assessment.
AB  - An overview is provided on the development of field equipment, instrument
      systems, and methods of analyses that were used to assess the impact of
      radioactive fallout from atmospheric weapons tests. Included in this review are
      developments in fallout collection, aerosols measurements in surface air, and
      high-altitude sampling with aircraft and balloons. In addition, developments in
      radiation measurements are covered in such areas as survey and monitoring
      instruments, in situ gamma-ray spectrometry, and aerial measurement systems. The
      history of these developments and the interplay with the general advances in the
      field of radiation and radioactivity metrology are highlighted. An emphasis is
      given as to how the modifications and improvements in the instruments and methods
      over time led to their adaptation to present-day applications to radiation and
      radioactivity measurements.

PMID- 12003013
TI  - Laboratory analyses: environmental and biological measurements.
AB  - From its inception in 1951 to the present, the measurement of radioactive fallout
      from nuclear weapons testing and the many associated programs to establish global
      distribution and human health effects have contributed significantly to the
      understanding of worldwide dispersal of contamination. The original measurements
      of regional surface deposition of fallout nuclides were with duplicate gummed
      film collectors. Later, collectors were established in a worldwide network to
      measure total deposition and specific radionuclides such as 90Sr and 137Cs, which
      evolved into the first large-scale, global environmental monitoring network.
      Programs were set up to determine dietary intake and human and animal tissue
      distribution of 90Sr and 137Cs. Some of the first measurements of natural
      background dietary radium and body potassium were a response to identify analog
      elements. The impact of the environmental measurements made for fallout went far
      beyond any dosimetric consequences. For example, present day information on bone
      tissue turnover rates are derived mainly from radiochemical analysis of 90Sr
      measurements in human bone. The spin off from the enormous expenditure in effort
      to make these measurements and to determine the health consequences of global
      fallout laid a rich basic and applied scientific foundation in many disciplines,
      particularly in exposure pathways from ground deposition to dietary uptake and
      human organ biokinetics.

PMID- 12003014
TI  - Meteorological benefits from atmospheric nuclear tests.
AB  - The presence in the atmosphere of radioactive debris from nuclear tests provided
      a unique opportunity to study atmospheric motions and transfers of trace
      substances. Measurements of the concentrations in air of radionuclides were used
      to verify trajectories derived solely from weather data. The profiles of
      radioactive concentration along the aircraft tracks were non-Gaussian. High
      flying aircraft and balloons collected air and particulate samples to
      approximately 30,000 m from Alaska to South America. The measurements from these
      samples were used in verifying stratospheric motions on a hemispheric and global
      scale. Other benefits to the atmospheric sciences gained during the nuclear
      testing era are briefly described.

PMID- 12003015
TI  - Worldwide dispersion and deposition of radionuclides produced in atmospheric
      tests.
AB  - Radionuclides produced in atmospheric nuclear tests were widely dispersed in the
      global environment. From the many measurements of the concentrations in air and
      the deposition amounts, much was learned of atmospheric circulation and
      environmental processes. Based on these results and the reported fission and
      total yields of individual tests, it has been possible to devise an empirical
      model of the movement and residence times of particles in the various atmospheric
      regions. This model, applied to all atmospheric weapons tests, allows extensive
      calculations of air concentrations and deposition amounts for the entire range of
      radionuclides produced throughout the testing period. Especially for the shorter
      lived fission radionuclides, for which measurement results at the time of the
      tests are less extensive, a more complete picture of levels and isotope ratios
      can be obtained, forming a basis for improved dose estimations. The contributions
      to worldwide fallout can be inferred from individual tests, from tests at
      specific sites, or by specific countries. Progress was also made in understanding
      the global hydrological and carbon cycles from the tritium and 14C measurements.
      A review of the global measurements and modeling results is presented in this
      paper. In the future, if injections of materials into the atmosphere occur, their
      anticipated motions and fates can be predicted from the knowledge gained from the
      fallout experience.

PMID- 12003016
TI  - A millennium perspective on the contribution of global fallout radionuclides to
      ocean science.
AB  - Five decades ago, radionuclides began to enter the ocean from the fallout from
      atmospheric nuclear weapons tests. The start of the 21st century is an
      appropriate vantage point in time to reflect on the fate of this unique suite of
      manmade radionuclides--of which more than two-thirds arrived at the surface of
      the oceans of the planet. During these five decades much has been learned of the
      behavior and fate of these radionuclides and, through their use as unique
      tracers, of how they have contributed to the growth of basic knowledge of complex
      oceanic physical and biogeochemical processes. Some of the highlights of the ways
      in which fallout radionuclides have given new insights into these processes are
      reviewed in the historical context of technological and basic ocean science
      developments over this period. The review addresses major processes involved,
      such as physical dispersion and mixing, particle association and transport of
      reactive nuclides, biological interactions, and mixing and burial within ocean
      sediments. These processes occur over a range of scales ranging from local to
      global. Finally, an account is given of the present spatial distribution within
      the oceans of the various components of the fallout radionuclide suite.

PMID- 12003017
TI  - Movement of radionuclides in terrestrial ecosystems by physical processes.
AB  - Physical processes that effect the movement of radionuclides in the temperate
      environments post-deposition are considered in this paper. The physical processes
      considered include the interception of radionuclides by vegetation, resuspension,
      and vertical migration in soil. United States and Russian results on the
      interception of radionuclides are reviewed and defined in terms of models that
      are currently undergoing evaluation and revision. New results on resuspension are
      evaluated, and a preliminary new model for the time-dependent resuspension factor
      is proposed. Chernobyl-related results on the movement of radionuclides into the
      soil column are presented, as is a revised model for this process based upon
      recent results from Ukraine.

PMID- 12003018
TI  - Food chains and biogeochemical pathways: contributions of fallout and other
      radiotracers.
AB  - This paper reviews examples of how measurements of global fallout in the
      environment and related tracer radionuclides have been used to enhance our basic
      knowledge of biogeochemical processes and food-chain pathways. Because it is
      these fundamental, natural processes that control the transport and accumulation
      of such trace substances in the environment, direct measurements of trace
      substances over time and space reveal strong insights into these processes. The
      necessity to monitor global fallout transport, although largely motivated by
      human health concerns, gave rise to a plethora of new information about plants,
      animals, and natural and agricultural ecosystems and how they function. This
      review provides a small selection of examples in the areas of plant and animal
      physiology, productivity and energy transfer in food chains, biogeochemical
      cycles of certain elements and their analogues, feeding relationships and
      movements of organisms, and the agriculture-based human food chain. It is
      concluded that if society is to cope successfully with continued growth of the
      human population and resource consumption, more knowledge is still required about
      these fundamental processes. The use of radiotracers can contribute greatly to
      this need, but current funding priorities, societal attitudes, and onerous
      regulations on the use of radioactivity may continue to limit such applications.

PMID- 12003019
TI  - Estimates of doses from global fallout.
AB  - This paper summarizes information about external and internal doses resulting
      from global fallout and presents preliminary estimates of doses resulting from
      intermediate fallout in the contiguous United States. Most of the data on global
      fallout were extracted from the reports of the United Nations Scientific
      Committee on the Effects of Atomic Radiation, in which the radiation exposures
      from fallout have been extensively reviewed at regular intervals. United Nations
      Scientific Committee on the Effects of Atomic Radiation estimated the average
      effective doses received by the world's population before 2000 to be about 0.4
      mSv from external irradiation and 0.6 mSv from internal irradiation, the main
      radionuclide contributing to the effective dose being 137Cs. Effective doses
      received beyond 2000 result mainly from the environmentally mobile, long-lived
      14C and amount to about 2.5 mSv summed over present and future generations.
      Specific information about the doses from fallout received by the United States
      population is based on the preliminary results of a study requested by the U.S.
      Congress and conducted jointly by the Centers for Disease Control and Prevention
      and the National Cancer Institute. Separate calculations were made for the tests
      conducted at the Nevada Test Site and for the high-yield tests conducted mainly
      by the United States and the former Soviet Union at sites far away from the
      contiguous United States (global tests). The estimated average doses from
      external irradiation received by the United States population were about 0.5 mGy
      for Nevada Test Site fallout and about 0.7 mGy for global fallout. These values
      vary little from one organ or tissue of the body to another. In contrast, the
      average doses from internal irradiation vary markedly from one organ or tissue to
      another; estimated average thyroid doses to children born in 1951 were about 30
      mGy from Nevada Test Site fallout and about 2 mGy from global fallout.

PMID- 12003020
TI  - Radiation doses to local populations near nuclear weapons test sites worldwide.
AB  - Nuclear weapons testing was conducted in the atmosphere at numerous sites
      worldwide between 1946 and 1980, which resulted in exposures to local populations
      as a consequence of fallout of radioactive debris. The nuclear tests were
      conducted by five nations (United States, Soviet Union, United Kingdom, France,
      and China) primarily at 16 sites. The 16 testing sites, located in nine different
      countries on five continents (plus Oceania) contributed nearly all of the
      radioactive materials released to the environment by atmospheric testing; only
      small amounts were released at a fewother minor testing sites. The 16 sites
      discussed here are Nevada Test Site, USA (North American continent), Bikini and
      Enewetak, Marshall Islands (Oceania); Johnston Island, USA (Oceania), Christmas
      and Malden Island, Kiribati (Oceania); Emu Field, Maralinga, and Monte Bello
      Islands, Australia (Australian continent); Mururoa and Fangataufa, French
      Polynesia (Oceania), Reggane, Algeria (Africa), Novaya Zemlya and Kapustin Yar,
      Russia (Europe), Semipalatinsk, Kazakhstan (Asia), and Lop Nor, China (Asia).
      There were large differences in the numbers of tests conducted at each location
      and in the total explosive yields. Those factors, as well as differences in
      population density, lifestyle, environment, and climate at each site, led to
      large differences in the doses received by local populations. In general, the
      tests conducted earliest led to the highest individual and population exposures,
      although the amount of information available for a few of these sites is
      insufficient to provide any detailed evaluation of radiation exposures. The most
      comprehensive information for any site is for the Nevada Test Site. The
      disparities in available information add difficulty to determining the radiation
      exposures of local populations at each site. It is the goal of this paper to
      summarize the available information on external and internal doses received by
      the public living in the regions near each of the mentioned nuclear test sites as
      a consequence of local fallout deposition.

PMID- 12003021
TI  - Health effects from fallout.
AB  - This paper primarily discusses health effects that have resulted from exposures
      received as a result of above-ground nuclear tests, with emphasis on thyroid
      disease from exposure to 131I and leukemia and solid cancers from low dose rate
      external and internal exposure. Results of epidemiological studies of fallout
      exposures in the Marshall Islands and from the Nevada Test Site are summarized,
      and studies of persons with exposures similar to those from fallout are briefly
      reviewed (including patients exposed to 131I for medical reasons and workers
      exposed externally at low doses and low dose rates). Promising new studies of
      populations exposed in countries of the former Soviet Union are also discussed
      and include persons living near the Semipalatinsk Test Site in Kazakhstan,
      persons exposed as a result of the Chernobyl accident, and persons exposed as a
      result of operations of the Mayak Nuclear Plant in the Russian Federation. Very
      preliminary estimates of cancer risks from fallout doses received by the United
      States population are presented.

PMID- 12003023
TI  - Secretary Abraham recommends Yucca Mountain site.

PMID- 12003022
TI  - A perspective on public concerns about exposure to fallout from the production
      and testing of nuclear weapons.
AB  - Exposures of the American public occurred nationwide from the testing of nuclear
      weapons in the United States, the Pacific, and the former Soviet Union. After
      decades of diminished public awareness on the subject of health risks resulting
      from exposure to fallout, the release of the National Cancer Institute's 1997
      report on nationwide exposure to 131I from the Nevada Test Site (NTS) has led to
      renewed interest. Public requests for information are focused on individual and
      family health problems, the right to credible and full disclosure of information,
      and the need for medical care and assistance for exposure-related health
      problems. Public concerns have been raised regarding: (a) the lack of information
      on the potential health risks from exposure to all biologically significant
      radionuclides in fallout; (b) the lack of independent oversight that includes
      public participation; (c) governmental portrayal of exposures averaged over very
      large segments of the population without identification of much larger values for
      individuals or population subgroups likely to be at highest risk; and (d) a
      governmental response to known or suspected human exposures that consumes large
      periods of time and devotes considerable funding to various research-related
      activities before serious consideration is given to addressing health care
      responsibilities to exposed individuals. To some extent, these complaints and
      concerns are rooted in the legacy of government secrecy surrounding the
      development and testing of nuclear weapons, public distrust of government sources
      of information about radiation exposures and health risks, and the imposition of
      past exposures without informed consent. Members of the public participating in
      the oversight of dose reconstruction projects and epidemiologic studies are
      requesting information on the total impact from all relevant sources of exposure
      at each site that might contribute significantly to an individual's risk,
      including exposure to local releases and to NTS and global fallout. Information
      is being requested on individual doses and risks from these cumulative exposures,
      with estimates of uncertainty, including estimates of the absorbed organ dose (as
      opposed to the effective dose), the risk of disease incidence as opposed to the
      risk of a cancer fatality, and the chance that a person's diagnosed disease was
      caused by past exposure (i.e., the probability of causation). This paper attempts
      to address some of these concerns. We conclude by noting that many individuals
      exposed in childhood during the 1950's to 131I in fallout from nuclear weapons
      production and testing would qualify for compensation and medical care if the
      present rules for the adjudication of claims for atomic veterans and radiation
      workers at DOE sites were to be extended to the public.

PMID- 12003024
TI  - NRC orders NPP security enhancement. Nuclear Regulatory Commission.

PMID- 12003025
TI  - Timer to shut off portable air samplers.
AB  - Portable air samplers used at Los Alamos National Laboratory produce noise levels
      that make it difficult to conduct classes or tours in their vicinity. If air
      samplers are shut off during a class or tour, it may not be restarted at the end
      of the class or tour, preventing detection of low level airborne contamination or
      the measurement of a more significant release during a later operation. To enable
      clear communication during tours and classes a timer was designed and constructed
      that allows an air sampler to be shut of for a short, fixed duration and
      automatically restarted. A schematic and parts list is included.

PMID- 12003026
TI  - Preliminary measurements of surface removable NORM activity in the WIPP
      underground.
AB  - The results of correlating surface removable activity to that measured on a fixed
      air sampler is reported. It was found from over 40 smears taken during a two week
      period that surface removable activity from Naturally Occurring Radioactive
      Material (NORM) can be predicted to be within a factor of 2 or 3 using either a
      fixed air sampler measurement or even another smear measurement from a specified
      surface. The method is being used to take credit for background surface removable
      activity in similar fashion to a background count for any other radiation
      detector. The utility of this technique is also discussed from an operational
      health physics perspective for the Waste Isolation Pilot Plant.

PMID- 12003027
TI  - Radioactive waste minimization at a large academic medical facility.
AB  - The University of Texas Medical Branch (UTMB) at Galveston is a large academic
      medical center with about 12,700 employees, 350 radioisotope research labs and
      200 permitted radioactive materials users. Consequently, UTMB generates a fairly
      large amount of radioactive waste. The majority of this waste contains short
      lived radionuclides, such as 32P, 33P, and 35S, which are held for decay and then
      disposed at a sanitary landfill. However, some waste, including long-lived waste
      and stock vials, is compacted into drums and stored in a warehouse facility, on
      site, until disposal at a low-level radioactive waste (LLRW) facility. Space in
      the warehouse is limited but disposal is currently cost prohibitive. A
      reevaluation of our program was conducted to see if volumes of LLRW requiring
      disposal at a commercial LLRW facility could be reduced. A reevaluation of the
      waste streams resulted in the shifting of most of the material that was being
      drummed for shipment to a LLRW facility to disposal by landfill or incineration.
      Materials that were previously assumed to be radioactive are now being evaluated
      prior to disposal to determine if they may be disposed of as non-radioactive
      waste. Following the initial evaluation, the amount of compacted dry solids
      assumed to contain long-lived radionuclides was reduced. The space that was saved
      due to the decrease in drumming for disposal is now used to hold the increased
      volume of decay-in-storage material. The monetary savings will amount to about
      $45,000 per year. This program is currently being expanded to reduce other waste
      streams at the university.

PMID- 12003028
TI  - Our way of life has changed forever.

PMID- 12003029
TI  - Interview with Peter G. Vernig.

PMID- 12003030
TI  - Interview with Victor N. Evdokimoff.

PMID- 12003031
TI  - Handling, storage, treatment, and disposal of mixed wastes at medical facilities
      and academic institutions.
AB  - Mixed waste includes hazardous/ toxic chemicals and radioactive materials mixed
      together. Most mixed wastes are difficult and costly to work with safely. Meeting
      the legal and regulatory requirements to generate, use, store, treat, and dispose
      of mixed waste can also be costly and difficult. The regulations that govern
      mixed waste, from creation to final disposition, are extensive and complex to
      implement. Complete and documented compliance with the applicable regulations is
      essential to demonstrate that personnel and environment safety has been assured.
      Noncompliance with the multitude of government's requirements for mixed waste can
      lead to serious repercussions. Noncompliance may cause serious harm to
      individuals and the environment, fines and penalties against a facility, and/or
      suspension of a facility's operations. Each facility that generates, uses, or
      possesses mixed waste must employ adequate expertise to assure full regulatory
      compliance. This paper introduces the large scope and variety of mixed waste and
      the current and potential methods to treat and ultimately dispose of, or recycle,
      mixed waste. Alternatives for regulatory compliance are also discussed and
      effective means to control mixed waste are presented. The paper is based on my
      Master's Thesis (Hageman 2001).

PMID- 12003032
TI  - Managing a low-level mixed waste storage facility: a checklist for compliance to
      40 CFR 266.
AB  - Do you hold radioactive material for storage and decay before disposal? Does your
      material contain any hazardous chemical as defined by the EPA? You may need to
      take a closer look at the Final Rule published by the EPA in the May 16, 2001
      Federal Register.

PMID- 12003033
TI  - The reactor facility that was built at Columbia University but never used.
AB  - A large and heavy experimental plasma vessel is located on the second floor of
      the Engineering Building at Columbia University. It sits atop the concrete shell
      of the old nuclear reactor facility. The reactor facility was built many years
      ago but no nuclear fuel was ever loaded into it. It was designed to contain a 250
      kW reactor core. However, due to certain circumstances, it was never fueled or
      operated. This paper describes the events leading to the decision to not put the
      reactor into operation.

PMID- 12003034
TI  - Lead equivalence in glass: the default value vs. a defined value.
AB  - To most health physicists, the specification of lead-equivalent thickness in a
      glass viewing window is a request for equal attenuation by the glass and sheet
      lead of the same stated thickness. A failure to specify the energy at which
      equivalence is desired can lead to a significant deviation from the intended
      attenuation value. The reason for this is an alternative or "default" definition
      of lead equivalence that is used by the glass suppliers when the energy
      information is omitted.

PMID- 12003035
TI  - An initial radiation safety needs assessment of Costa Rica: the South Texas
      Chapter of the Health Physics Society's strategic planning appraisal for
      participation in the "Radiation Safety Without Borders" initiative.
AB  - In response to the Health Physics Society's recent 'radiation safety without
      borders" initiative, the South Texas Chapter of the Health Physics Society
      selected Costa Rica as its partner country of choice. To develop an understanding
      of the radiation safety needs of this country, the fall 2001 University of Texas
      Health Science Center at Houston School of Public Health Environmental Radiation
      and Radioactivity class was tasked with the assignment of assessing the possible
      radiation safety needs and concerns for this country. The assignment culminated
      in a class presentation to the membership of the South Texas Chapter during its
      annual fall meeting. Using library and web based resources, tile students
      reviewed a number of public health and radiation-related topics. Life
      expectancies were found to be equivalent to the United States, even though
      significant differences in per capita health expenditures were noted. Costa Rica
      exhibited lower population mortality rates from major causes such as
      cardiovascular diseases, neoplasms, and external sources. Maternal and infant
      mortality rates were found to be much higher in Costa Rica than in the United
      States. Naturally occurring radiation sources such as uranium deposits were not
      identified as apparent major radiation issues of concern, although ultraviolet
      radiation exposures are consistently high. Several recent events in the country
      and the region involving patient overexposures suggest that concerns are likely
      focused on ensuring the proper use and maintenance of healing arts radiation
      equipment. The lack of available information on radioactive waste disposal
      suggests that waste handling also may be an issue warranting attention. The
      exercise proved to be very educational for the students, and the information
      gathered will serve to focus the Chapter's efforts when technical exchanges are
      initiated. The importance of linking this initiative to other existing programs
      within the country is also discussed.

PMID- 12003036
TI  - Health physics technician injury reduction.
AB  - As part of a safety summit sponsored by Fluor Hanford Occupational Health and
      Safety, it was noted that Health Physics Technicians (HPTs) have one of the
      highest injury rates at Hanford. A multi-disciplined team made up of HPTs, health
      physics professionals, health physics management, indostrial hygienists, and
      medical personnel was established to determine causes and corrective actions.
      Committee activities included reviewing and characterizing occupational injuries
      and illnesses, assessing areas affecting the health of HPTs, soliciting field
      input, performing field evaluations of tasks, and making recommendations for
      improvements to senior management. Five areas showed a need for immediate
      improvement: manmachine interface (human factors and ergonomics), work
      environment, procedures, people, and communications. A key area of risk
      identified is the lack of ergonomic design considerations of the survey
      instruments currently used. There are several cases of cumulative trauma disorder
      requiring surgery. These cases are directly related to use of health physics
      instrumentation and/or survey techniques. The committee has made ergonomics and
      instrument redesign/modification its key initiative for 2001. The committee is
      encouraging vendor support and is seeking feedback from other health physics
      organizations regarding their experience and any recommendations they would like
      to make. Some success has already been achieved through an ergonomics-training
      program aimed at all HPTs and their supervisors. In addition, there have been
      several changes made to the way surveys are conducted, survey frequencies have
      been reduced, and the way modifications have been made to existing
      instrumentation. This is a long-term initiative with broad support within the
      Hanford HPT community. This document reports the progress made thus far on the
      initiative.

PMID- 12003037
TI  - Mobilization of state program resources for a steel mill accident.
AB  - Radioactive materials in scrap metal are a serious problem for dealers and
      processors as well as for state radiation protection programs. Most large dealers
      and processors have monitoring devices that detect radiation sources at their
      scale house or feed to the furnaces. For example, in Florida since July 1995, a
      fiscal year average of 41 such alarms has been reported to the Department of
      Health's Bureau of Radiation Control. The majority of these alarms involve small
      amounts of radioactive material, usually naturally occurring radioactive material
      such as 226Ra, contained in luminous dials or scale associated with mining
      activities in the state. Occasionally, industrial devices that contain
      radioactive source material are found. The Bureau classifies these alarms as
      incidents, and inspectors are dispatched to help identify the source and
      determine the disposition of the material. On 13 July 2001, a steel mill in north
      Florida reported that a 137Cs source had been melted in their furnace. This paper
      describes the actions undertaken by the Bureau in assessing the extent of
      contamination and subsequent cleanup activities undertaken by the mill.

PMID- 12003038
TI  - Emerging waterborne infections: contributing factors, agents, and detection
      tools.
AB  - Because microorganisms are easily dispersed, display physiological diversity, and
      tolerate extreme conditions, they are ubiquitous and may contaminate and grow in
      water. The presence of waterborne enteric pathogens (bacteria, viruses, and
      protozoa) in domestic water supplies represents a potentially significant human
      health risk. Even though major outbreaks of waterborne disease are comparatively
      rare, there is substantial evidence that human enteric pathogens that are
      frequently present in domestic water supplies are responsible for low-level
      incidence of waterborne microbial disease. Although these diseases are rarely
      debilitating to healthy adults for more than a few hours to a few days, enteric
      pathogens can cause severe illness, even death, for young children, the elderly,
      or those with compromised immune systems. As the epidemiology of waterborne
      diseases is changing, there is a growing global public health concern about new
      and reemerging infectious diseases that are occurring through a complex
      interaction of social, economic, evolutionary, and ecological factors. New
      microbial pathogens have emerged, and some have spread worldwide. Alternative
      testing strategies for waterborne diseases should significantly improve the
      ability to detect and control the causative pathogenic agents. In this article,
      we provide an overview of the current state of knowledge of waterborne microbial
      pathogens, their detection, and the future of new methods in controlling these
      infectious agents.

PMID- 12003039
TI  - Development and evaluation of pneumococcal conjugate vaccines: clinical trials
      and control tests.
AB  - Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and otitis
      media and is responsible for disease in young children, the elderly, and
      immunocompromised individuals. Emerging high-level resistance to penicillin,
      multiple antibiotics, and tolerance to vancomycin emphasizes the importance of
      preventing pneumococcal infection by alternative methods such as immunization.
      The development of pneumococcal conjugate vaccines using the same carrier
      proteins as those used in Hemophilus influenzae type b vaccines has enhanced the
      immune response in infants and children compared with polysaccharide vaccines and
      has significantly improved the ability to prevent pneumococcal disease in this
      population worldwide. Here we review the clinical trials of multivalent
      pneumococcal conjugate vaccines under evaluation, identify potential carrier
      proteins considered for development of future pneumococcal conjugate vaccines,
      discuss issues regarding licensure of new candidate vaccines from a clinical
      trial and quality control perspective, and alternative vaccine strategies for the
      prevention of pneumococcal disease.

PMID- 12003040
TI  - Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1): a new toxin
      with an old twist.
AB  - Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1) is a small
      protein that was first detected more than a decade ago in an enteroaggregative E.
      coli (EAEC) strain isolated from the stools of a diarrheic child. The EAST1 gene,
      astA, is not solely present in EAEC, but also in other categories of
      diarrheagenic E. coli. Strains expressing EAST1 have been shown to induce
      diarrhea principally in humans, although they have also been associated with
      piglets and calves. EAST1 toxin has been proposed as a virulence factor
      implicated in the mechanism of pathogenesis of EAEC and could play a role in the
      pathogenicity of other enteropathogens as well. This toxin is often compared to
      E. coli STa enterotoxin because they share some physical and mechanistic
      similarities. This review summarizes the various observations on EAST1 since its
      discovery.

PMID- 12003041
TI  - Control of the bacterial cell cycle by cytoplasmic growth.
AB  - For free-living single-celled organisms, it can be assumed that it is their
      success in acquiring resources and converting them into cytoplasm that controls
      the timing of their cell cycles. Cytoplasm is the sink for the bulk of the
      environmental resources. It must be the case that this type of control must
      operate in dilute cultures under adequate nutrition in a constant environment. It
      follows that there ought to be mechanisms that measure or count the cell's
      biomass or some component of the cytoplasm to measure their growth success.
      Besides sensing their biomass, they need to know when a certain value of the cell
      size has been achieved. When this critical state has been achieved, the cell
      needs to have an all-or-none trigger that either initiates chromosome
      replication, the completion of cell replication, cell division, or the process of
      separating sister cells physiologically or physically. Any of these four
      different stages, in principle, may be the one triggered in response to cell
      growth in different species of microorganisms. Alternatively, multiple triggers
      at different cell sizes may be activated at different cell cycle stages. Although
      initiation of chromosome replication has been believed to be the event triggered
      in Escherichia coli, this probably is not generally the case and other control
      mechanisms may act in other prokaryotes. How the increase in cell biomass is self
      assessed and used to carry out critical cell cycle events is not understood in
      any case. This deficiency in our knowledge of microbial cell physiology is grave.
      The factor that probably has prevented the elucidation of the mechanisms in any
      organism is that enzymatic processes deal with concentrations, and a cell cycle
      trigger must respond to the total amount of material present in a cell. This
      article discusses the theoretically possible classes of mechanisms for the cell
      to respond when it has achieved its appropriate critical size. These breakdown
      into three groups: those mechanisms that assess the total amount of biomass or
      some special subcellular component, and those that measure the ratio of one
      component to another component where their two syntheses are differently
      controlled by cell physiology and morphology, and a third group with some
      specialized mechanisms.

PMID- 12003042
TI  - Inguinal hernia: the size of the mesh.
AB  - The size of the mesh used for surgical repair of groin hernias differs
      significantly from one technique to another. Such differences are not
      unimportant, since implantation of a large amount of prosthetic material can
      induce some drawbacks and may perhaps be avoided in many cases. The weak inguinal
      area, where inguinal hernias are exteriorized, is smaller than the myopectineal
      orifice, and a mesh 8-9 cm long and 5-6 cm wide is sufficient to cover this area.
      The results of methods using a small mesh are good, and large patches provide at
      best the same results with some real drawbacks. A large mesh spread in the
      preperitoneal space on the bladder and iliac vessels can induce some difficulties
      in case of further operation on these organs, and when we operate on a man 30 to
      50 years old, we ignore whether he may need that kind of operation many years
      later. Consequently, in most cases a small patch covering only the weak inguinal
      area is preferable and a large preperitoneal patch should be used only in
      selected cases at high risk of recurrence.

PMID- 12003043
TI  - Incidence and predisposing factors for incisional hernia in patients with liver
      transplantation.
AB  - BACKGROUND: Cirrhotic patients who are transplanted have a high risk of
      developing incisional hernia (IH). MATERIALS AND METHODS: We have analysed the
      incidence and treatment of IH in 465 patients with liver transplantation (LT). In
      order to find predisposing factors, we compared these patients with a similar
      group of patients with LT without IH. Fifty-four patients (11.6%) developed an
      IH. Forty-six of these (85%) were males, and in 37% the entire laparotomy
      incision was involved. Forty patients have been operated on for the hernia, three
      by primary repair and 37 (92.5%) with a polypropylene mesh. After a follow-up of
      42 months, 6 (15%) IHs recurred. Comparing groups, IH patients were older
      (P<0.05), of male gender (P<0.001), and received more steroids (P<0.01). The IH
      rate was not related to suture material. CONCLUSIONS: Our rate of IH is perhaps
      reasonable in these high risk patients. It appears that IH can be reduced if
      steroids are reduced or avoided. We recommend a large mesh for repair.

PMID- 12003044
TI  - Preperitoneal mesh hernioplasty in giant inguinoscrotal hernias: a new technique
      with dual benefit in repair and abdominal rooming.
AB  - To solve the problem of limited abdominal cavity in cases of giant inguino
      scrotal hernias, a new technique is described, aiming, while repairing the
      hernia, to provide a larger abdominal cavity into which the hernial contents can
      be replaced without compromising respiratory and cardiac functions. The idea of
      this technique is to create a midline abdominal wall defect to increase the intra
      abdominal capacity to accommodate the hernial contents. The hernial sac is then
      pulled up to the abdomen and fashioned as a rotation flap to augment and close
      the peritoneum over the replaced contents. Lastly, a giant Polypropylene mesh is
      inserted in the preperitoneal space to cover the created midline defect and to
      buttress both inguinal regions. Eight patients with giant inguinoscrotal hernias
      were operated upon using this technique. The results showed that the procedure is
      safe and all postoperative complications (three seromas, two wound infections,
      and two cases of severe scrotal edema) were treated conservatively. All patients
      were discharged home within 7-15 days and no recurrences have been reported in a
      follow-up period of between 2 and 4 years. In addition to repairing hernial
      defects, this new technique allows reduction of massive hernias without
      compromising respiratory and cardiac functions by enlarging the shrunken
      peritoneal cavity before returning the hernia's contents. Moreover, in covering
      the abdominal defect which has been created by the hernial sac, direct contact
      between the intestine and the mesh is prevented, thus minimizing the risk of
      adhesions and fistulas.

PMID- 12003045
TI  - A university experience using mesh in inguinal hernia repair.
AB  - In a university program, surgical residents are trained to perform classic
      inguinal hernia repair. The necessity of this approach is discussed. In this
      study, polypropylene mesh was added to the repair in order to familiarize the
      resident with the properties and qualities of mesh. Three hundred seventy-one
      consecutive herniorrhaphies were performed using a precut mesh in patients
      weighing between 110 lbs and 285 lbs. All patients were seen postoperatively, and
      120 were seen at 1 year. One recurrence and no major complications were noted.
      Deficient local collagen and properties of mesh prosthetics are discussed as part
      of the surgical resident curriculum.

PMID- 12003046
TI  - Plug repair of groin hernias: a 10-year experience.
AB  - From April 1990 to July 2000 we performed 4,024 hernia operations and implanted
      3,332 plugs in groin hernias. This technique was performed on a continuous,
      progressive basis. Between 1990 and 1994, the percentage of plugs was 67%, with
      the proportion rising to 92% since 1995. Although we initially used them only for
      indirect inguinal hernias (1990-1994), in 1995 we began inserting plugs in direct
      defects [Marlex Perfix Plug, (Bard Company, 78196 Trappes, France) January 1995
      July 1997]. On the basis of our own cases of recurrence, we reoperated and
      modified plugs using a new prosthesis (Obtura Mesh, Cousin Company, Wervicq Sud
      559558, France). Maximum follow-up was 10 years, with 84% of the patients
      followed for more than 1 year. Postoperative mortality was zero, local infection
      occurred in 20 patients (0.6%) and testicular atrophy was observed with 27
      patients (0.8%). The recurrence rate was 1.4%.

PMID- 12003047
TI  - Endoscopic repair of bilateral inguinal hernias--short and late outcome.
AB  - BACKGROUND: In the last decade there have been dramatic changes in the treatment
      of inguinal hernia with the introduction of mesh techniques including
      laparoscopic repair. There is still some controversy regarding the treatment of
      bilateral inguinal hernia but simultaneous operation has gained popularity. The
      aim of this study was to evaluate the outcome of laparoscopic simultaneous
      bilateral hernia with regard to complications, recurrence rate, and late
      discomfort. METHODS: A retrospective analysis was made of 168 patients operated
      simultaneously for bilateral inguinal hernia using the laparoscopic technique
      between October 1993 and December 1998. Complications were registered and a
      follow-up was performed using a combination of questionnaire and selective
      clinical examination. RESULTS: Complications were seen in 23 patients (13.8%),
      the majority minor. Ninety-five percent of the patients were followed for a
      median of 36 months. The recurrence rate was 2.7%. Twenty-six of the follow-up
      patients (15.5%) reported some discomfort. CONCLUSIONS: We conclude that
      simultaneous laparoscopic operation for bilateral inguinal hernia is safe, with
      complications, recurrence rate and late discomfort are equivalent to those seen
      after unilateral operation.

PMID- 12003048
TI  - Evolution of hernia repair: a salute to Professor Piero Pietri.
AB  - This subject has been well covered in recent years. Yet it seems appropriate to
      search for major advances in hernia methodology during the last 100 years.
      Eduardo Bassini is credited with pioneering the modern era. His "triple layer"
      repair was corrupted through the years and, as a result, he did not receive
      sufficient credit for his attention to the posterior inguinal wall. Chester
      McVay, renowned surgeon-anatomist, renewed interest in the Cooper's ligament and
      the posterior inguinal wall. Surgeons from the Universities of Washington and
      Illinois perfected approaches to the posterior inguinal wall. Thus, these
      investigators paved the way for several effective posterior hernia operations.
      The name of Usher will forever be remembered in terms of practical prosthetic
      mesh (polypropylene). This material, as well as others, has become an important
      addition to the surgeon's armamentarium. Rene Stoppa reminded us of the Pascal
      principle and clearly demonstrated how giant prostheses can remain in the
      preperitoneal space without the need for sutures. Tension-free operations, plug
      techniques, and laparoscopic hernia methodology must await further analysis.

PMID- 12003049
TI  - The contribution of Allison and Nissen to the evolution of hiatus herniorrhaphy.
AB  - Even though it was not until 1950 that Barrett introduced the term "reflux
      esophagitis", this entity is now the most common disease afflicting the western
      world. Diaphragmatic herniation, recognized by Sennertus in 1541, was first
      repaired by Potemski (1889). Before World-War II, the condition was considered
      rare; symptomatology, as in external herniae, was ascribed to pinching of the
      stomach by the hernial ring. Only large protrusions, with signs of impending
      incarceration, volvulus, or strangulation, were operated upon. Modern
      understanding derives from studies of short, strictured esophagi. Because of
      endoscopic "gastric" biopsies in children, Findlay and Kelly considered them
      congenital "misplacements". However, Allison (1943), finding adults with
      ulceration and scarring, argued they were acquired. Later (1953) he concluded
      that the distal esophagus may be lined with metaplastic adenomatous epithelium
      which can harbor malignancy. His repair, reestablishing the crural pinchcock was,
      as pointed out by his countryman Collis (who in 1957 constructed a neo-esophagus
      from the Magenstrasse), inadequate. Nissen performed (1936) gastroesophagectomy
      in a case of peptic ulceration of the cardia. To avoid leakage he buried the
      anastomosis. Amazingly, 17 years later he learned that the patient had no reflux.
      He then successfully performed and reported (1956) fundoplication in a man and
      woman with gastroesophageal reflux disease. His operation remains the basis for
      surgical therapy today.

PMID- 12003050
TI  - A Swedish thesis on groin hernia surgery.

PMID- 12003052
TI  - A comparison of an electronic version of the SF-36 General Health Questionnaire
      to the standard paper version.
AB  - Because of its sound psychometric properties the SF-36 General Health
      Questionnaire is used throughout the world, yet it is difficult to analyse and
      score. Using a newly developed software package, onto which any questionnaire can
      be loaded, we developed an electronic version of the SF-36 General Health
      Questionnaire. The purpose of this study is test the effect of the electronic
      mode of administration on the measurement properties of the SF-36. In a
      randomised cross-over design study 79 healthy individuals and 36 chronic pain
      patients completed both electronic and paper versions of the SF-36. Seventy-one
      percent preferred the electronic SF-36, 7% stated no preference, and 22%
      preferred the paper version. Completion time for the electronic SF-36 was
      slightly less, and there were no missing or problematical responses, whereas 44%
      of participants had at least one missing or problematical response in the paper
      version. Data entry and auditing time was 8 hours. There was less than 4% inter
      version difference for any of the SF-36 sub-scales. The electronic SF-36 was well
      accepted and slightly quicker to complete than the paper version. We conclude
      that the electronic SF-36 is equivalent in performance and more effective than
      the paper version.

PMID- 12003051
TI  - Using the standard error of measurement to identify important changes on the
      Asthma Quality of Life Questionnaire.
AB  - OBJECTIVES: To establish a link between the minimal important difference (MID)
      and the standard error of measurement (SEM) for all responsive dimensions of the
      Asthma Quality of Life Questionnaire (AQLQ). METHODS: Secondary data analysis of
      baseline and follow-up interview data from 198 outpatients with asthma enrolled
      in a randomized controlled trial and receiving care at a major urban academic
      medical center's general medicine clinics. Domain statistics for baseline and
      follow-up interviews were examined for the AQLQ. The baseline SEM values were
      compared with established AQLQ MID standards using weighted kappa values.
      RESULTS: One SEM identified the MID in responsive AQLQ dimensions. Weighted kappa
      values (0.88-0.93) validated excellent agreement between these two criteria.
      CONCLUSION: This is the third study to support using one SEM to identify
      important individual change in health-related quality of life (HRQoL) measures.
      However, refinement of the process for determining a measure's clinically
      meaningful differences is still needed to secure a link between the SEM and the
      identification of relevant HRQoL change over time.

PMID- 12003053
TI  - Rapid assessment of psychosocial well-being: are computers the way forward in a
      clinical setting?
AB  - OBJECTIVE: To compare the agreement between anxiety, depression and supportive
      care needs data obtained using a touchscreen computer survey with traditional pen
      and-paper surveys. METHODS: The sample consisted of 1,304 consecutive patients
      attending the medical or radiation oncology outpatient department in two public
      cancer treatment centres. Of the 357 eligible patients, 355 (99%) consented to
      participate and 350 (98%) completed both touchscreen computer and pen-and-paper
      versions of the Hospital Anxiety and Depression Scale (HADS) and short-form
      Supportive Care Needs Survey (SCNS-short). RESULTS: Simple kappa values indicated
      moderate agreement (X = 0.57) between the two modes of survey administration for
      most HADS items. Simple kappa coefficients indicated only fair agreement (X =
      0.28) when a simplified response option format was used in the computerised SCNS
      short. When the paper and computerised survey used the same response format,
      simple kappa coefficients increased and indicated moderate agreement (X = 0.44)
      for most SCNS-short items. Kappa coefficients indicated at least moderate
      agreement (kappa > 0.41) in identifying patients with elevated levels of anxiety
      and depression; there were no significant differences in the proportion of
      patients identified with elevated levels of anxiety and depression according to
      computer survey compared to paper survey. Prevalence-adjusted bias-adjusted kappa
      (PABAK) coefficients indicated at least moderate agreement (X = 0.79) in
      identifying participants with moderate/high levels of unmet needs. However,
      participants tended to report lower levels of unmet needs with a simplified
      response format in the computerised SCNS-short compared to the paper survey. This
      was not observed when the response format of the computerised SCNS-short
      replicated the paper survey. CONCLUSIONS: Despite the advantages that
      computerised surveys offer for simplifying survey presentation, current results
      suggest the need to exactly replicate the question and response option format of
      the original paper survey to ensure the data collected are equivalent. This
      finding is particularly important given the potential application of computerised
      surveys in the clinical setting to quickly assess and identify patients' concerns
      requiring intervention by health care providers.

PMID- 12003054
TI  - A new graphic for quality adjusted life years (Q-TWiST) survival analysis: the Q
      TWiST plot.
AB  - One of the challenges of interpreting a Quality-adjusted time without symptoms of
      disease and toxicity (Q-TWiST) analysis is examining the sensitivity of
      conclusions that may be drawn to varying values of the utility coefficients for
      days with toxicity and days after disease progression. We present a graphic that
      parsimoniously displays the impact on median Q-TWiST survival across treatment
      groups of varying values of the utility coefficients. The goal of the graphic is
      to present a concise Q-TWiST analysis. We use Zhao and Tsiatis (Biometrika 1997;
      84(2): 339-348) to adjust for the bias in Kaplan-Meier (K-M) estimates. The
      graphic contains bounds that approximate points for which statistical
      significance would be achieved by comparing the median Q-TWiST survival between
      treatment alternatives for each value of the utility coefficients. The plot may
      be generalized to compare Q-TWiST means, medians or percentiles across treatment
      groups. We demonstrate the application of the Q-TWiST plot through a re-analysis
      of a randomized phase III North Central Cancer Treatment Group (NCCTG) clinical
      trial of recombinant Interferon-2alpha in patients with malignant melanoma. We
      explore alternative options to customize the graphic representation for other
      data sets drawn from several NCCTG clinical trials.

PMID- 12003055
TI  - Measuring quality of life in children with inflammatory bowel disease: the impact
      II (NL).
AB  - Inflammatory bowel disease (IBD) is a chronic debilitating disorder. Measures of
      quality of life are only available for adult patient populations. We developed a
      new disease-specific health-related quality of life instrument in Dutch for
      pediatric patients with IBD, called Impact-II (NL). We translated and strongly
      modified the original (Canadian) Impact questionnaire. It comprises 35 items in
      six domains. Eighty-three children (66%) completed the questionnaire, 39 children
      were assessed twice. Disease symptoms were recorded and disease course severity
      assessed through chart review. Summated disease activity scores and disease
      course severity scores were dichotomized into two categories. Reliability
      coefficients were good for five out of six domains (Cronbach's alpha ranged from
      0.57 to 0.86) and measures of test-retest stability in clinically stable patients
      were good for all domains (intra-class correlation coefficients ranged from 0.67
      to 0.91). The instrument showed good discriminant validity between symptom groups
      and disease course severity on all domains. Convergent validity with a validated
      generic instrument [TNO-AZL Children's Quality of life questionnaire (Tacqol)]
      showed satisfactory coefficients. In conclusion, the developed questionnaire
      shows good psychometric properties. Test-retest stability and responsiveness to
      change should be further assessed in larger patient samples. Cross-cultural
      translation and validation procedures into other languages are being conducted to
      enable international use of Impact-II.

PMID- 12003056
TI  - Associations of self-reported oral health with physical and mental health in a
      nationally representative sample of HIV persons receiving medical care.
AB  - BACKGROUND: The impact of oral health on HIV patients has not been sufficiently
      documented. OBJECTIVE: To estimate the associations between measures of oral and
      generic health-related quality of life in persons receiving medical care for HIV.
      DESIGN: This is a longitudinal study of interview data collected in a probability
      sample of adults with HIV receiving health care in the US. The data were
      collected at three points in time. PATIENTS: Two thousand eight hundred and sixty
      four HIV-infected adults using medical care. MEASUREMENTS: Physical and mental
      health were assessed using 28 items and oral health was assessed using seven
      items on oral-related pain and discomfort, worry, appearance, and function.
      Clinical measures included CD4 count, oral symptoms, physical symptoms, and stage
      of HIV. Physical functioning and emotional well-being were measured on a 0-100
      scale with higher scores indicating better health. Oral health was measured using
      seven items with a five point scale. RESULTS: In multivariate analyses, oral
      symptoms had the strongest association with oral health-related quality of life.
      Each additional oral symptom was associated with an average decrease in oral
      health (0-100 possible range) of 3.97 points (p = 0.000). In addition, oral
      health was significantly associated with both physical and mental health. A one
      point increase in oral health was associated with a 0.05 (p = 0.000) increase in
      mental health and 0.02 increase in physical health (p = 0.031). CONCLUSIONS: Oral
      health is strongly associated with physical and mental health but provides
      noteworthy unique information in persons with HIV infection. Thus, physical and
      mental health measures of HIV patients should incorporate indicators of oral
      functioning and well-being.

PMID- 12003057
TI  - Content validity for dementia of three generic preference based health related
      quality of life instruments.
AB  - A semi-structured interview was conducted with dementia patients and their
      caregivers in order to explore which aspects of quality of life were perceived as
      relevant and important. These aspects of quality of life were compared with the
      content of three generic utility-based quality of life instruments: European
      Quality of Life Instrument, Health Utilities Index, and Quality of Well-Being
      (QWB) Scale. Twenty patients with mild dementia and 20 caregiver volunteers
      provided narrative data derived from interviews that were analyzed using a
      modified Grounded Theory method of analysis. Essential attributes of dementia
      quality of life identified by the respondents were missing in the three utility
      based quality of life instruments selected for the study. Patients provided a
      wider range of attributes than the instruments including some attributes not
      described by caregivers. Of the three utility-based measures, the QWB scale
      included the largest number of quality of life attributes but still missed many.
      Compared to the respondent generated attributes all three utility-based quality
      of life instruments have important shortcomings in content validity.

PMID- 12003058
TI  - Can improvement in well-being and functioning be distinguished from depression
      improvement in antidepressant clinical trials?
AB  - The Inventory of General Life Functioning (GLF), a self-evaluation scale for
      patients, was developed for use in the National Institute of Mental Health
      Treatment of Depression Collaborative Research Program. The scale was designed to
      evaluate patient general well-being and functioning, areas not adequately covered
      by standard depression scales. We used the patient self-report version of the GLF
      in two imipramine-controlled clinical trials during the development of the
      antidepressant venlafaxine. In these double-blind studies, outpatients with
      depression received placebo (n = 158), venlafaxine (n = 152), or imipramine (n =
      149) for up to 6 weeks. We examined the internal consistency and factor structure
      of the GLF, its correlation with standard depression rating scales, and its
      sensitivity to differential treatment effects. We found the scale to be
      internally consistent and moderately correlated with physician-rated measures of
      depression. A reported two-factor structure (general well-being and functioning)
      was evaluated by factor analysis. When analyses were restricted to patients who
      completed at least 4 weeks on therapy, the GLF displayed sensitivity to
      differential treatment effects. The GLF total and factor subscales demonstrated
      the superiority of an active therapy (venlafaxine) to placebo; the GLF factor and
      a 7-item subscale using only items derived from Dupuy's psychological general
      well-being index (PGWB) demonstrated an advantage for one active therapy
      (venlafaxine) over another (imipramine). The GLF is a useful complement to the
      standard depression rating scales because it may assess additional dimensions of
      the depressive syndrome.

PMID- 12003059
TI  - Molecular variation of Trypanosoma brucei subspecies as revealed by AFLP
      fingerprinting.
AB  - Genetic analysis of Trypanosoma spp. depends on the detection of variation
      between strains. We have used the amplified fragment length polymorphism (AFLP)
      technique to develop a convenient and reliable method for genetic
      characterization of Trypanosome (sub)species. AFLP accesses multiple independent
      sites within the genome and would allow a better definition of the relatedness of
      different Trypanosome (sub)species. Nine isolates (3 from each T. brucei
      subspecies) were tested with 40 AFLP primer combinations to identify the most
      appropriate pairs of restriction endonucleases and selective primers. Primers
      based on the recognition sequences of EcoRI and BglII were chosen and used to
      analyse 31 T. brucei isolates. Similarity levels calculated with the Pearson
      correlation coefficient ranged from 15 to 98%, and clusters were determined using
      the unweighted pair-group method using arithmetic averages (UPGMA). At the
      intraspecific level, AFLP fingerprints were grouped by numerical analysis in 2
      main clusters, allowing a clear separation of T. b. gambiense (cluster I) from T.
      b. brucei and T. b. rhodesiense isolates (cluster II). Interspecies evaluation of
      this customized approach produced heterogeneous AFLP patterns, with unique
      genetic markers, except for T. evansi and T. equiperdum, which showed identical
      patterns and clustered together.

PMID- 12003060
TI  - Detection of eight Cryptosporidium genotypes in surface and waste waters in
      Europe.
AB  - Cryptosporidia are important protozoan parasites of vertebrates, and a number of
      species and genotypes, with different host ranges, have been described. In this
      study a protocol was established for the detection and the genetic
      characterization of Cryptosporidium spp. isolated from various types of surface
      waters (rivers, creeks, lakes, sewage plant in- and outlets and swimming pools)
      from the area between Zurich (Switzerland) and Munich (Germany). Cryptosporidium
      oocysts were isolated by continuous-flow-centrifugation and immunomagnetic
      separation (IMS). A novel nested PCR combined with direct sequencing of the
      amplicon which spans a variable region of the 18S rRNA allowed characterization
      of species and genotypes. Cryptosporidium spp. were detected in 23 of the 68
      water samples investigated. Almost half of these isolates represent species and
      genotypes known to be pathogenic to man, namely C. parvum 'bovine genotype' (from
      6 samples) and C. parvum 'human genotype' (4). Furthermore, we identified C.
      muris 'genotype A' (3), C. muris 'genotype B' (6), C. baileyi (1) as well as 3
      novel Cryptosporidium genotypes. Our results confirm the ubiquitous presence of
      Cryptosporidium oocysts in surface waters. The detection of a variety of species
      and genotypes stresses the importance that molecular characterization is
      indispensable before drawing conclusions of medical or epidemiological
      significance.

PMID- 12003061
TI  - Description of Enteromyxum scophthalmi gen. nov., sp. nov. (Myxozoa), an
      intestinal parasite of turbot (Scophthalmus maximus L.) using morphological and
      ribosomal RNA sequence data.
AB  - A new Myxozoa species causing enteritis and death in cultured turbot,
      Scophthalmus maximus, is described at light and electron microscope levels. In
      addition, small subunit ribosomal RNA gene sequences (SSU rDNA) from the new
      species and from similar myxozoans were obtained and used for phylogenetic
      inference, as complementary criteria to resolve its taxonomic classification. The
      new parasite is closely related to Myxidium leei, another enteric histozoic
      species from marine fish. However, the ascription of M. leei to the genus
      Myxidium was based on weak morphological evidence and is not supported by our
      rDNA data analysis. A close relationship with Zschokkella, the other
      morphologically related myxozoan genus is also not supported. The combined
      morphological and molecular study results in the establishment of the new genus
      Enteromyxum to accommodate the new species E. scophthalmi, and the former M.
      leei, which is transferred to the new genus as Enteromyxum leei (Diamant, Lom &
      Dykova 1994) n. comb. This genus of marine, histozoic and enteric myxozoans
      includes significant parasite species for marine finfish culture.

PMID- 12003062
TI  - Small subunit ribosomal DNA phylogeny of microsporidia that infect Daphnia
      (Crustacea: Cladocera).
AB  - Glugoides intestinalis, Microsporidium sp., Ordospora colligata, Gurleya vavrai,
      Larssonia obtusa and Flabelliforma magnivora are microsporidian parasites of
      planctonic freshwater crustaceans Daphnia spp. We performed a phylogenetic
      analysis of the small subunit ribosomal DNA which revealed their positions as
      polyphyletic. G. intestinalis, Microsporidium sp. and O. colligata, which are
      horizontally transmitted gut parasites with small spores and low virulence, group
      with different lineages. G. intestinalis is related to 2 microsporidia infecting
      lepidopterans and to Vittaforma corneae, which has been described as a human
      pathogen. It is thought that V. corneae may have an invertebrate as its natural
      host. Microsporidium sp. is a relative of the genera Enterocytozoon and
      Nucleospora, pathogens of man and fish respectively. O. colligata is the first
      species found to be closely related to the genus Encephalitozoon, which is
      comprised of 3 species that are parasites of homeothermic vertebrates. G. vavrai
      and L. obtusa are sister taxa that branch close to the Amblyosporidae, the only
      microsporidia with known intermediate hosts. This finding supports the
      presumption of secondary hosts for G. vavrai and L. obtusa, as it has not been
      possible to maintain these species in Daphnia in the laboratory. F. magnivora
      roots deep at the base of the phylum microsporidia with no close relative found
      so far.

PMID- 12003063
TI  - Proteins and proteinases in the in vitro released products (IVRP) of the tissue
      invasive and lung-dwelling larvae of the pentastomid Porocephalus crotali.
AB  - Pentastomids are arthropod-like parasites which inhabit the respiratory tract of
      tetrapods and, despite being haematophagous, cause little or no visible
      pathology. Nymphs (or larvae), belonging to the advanced genus Porocephalus,
      encyst in the tissues of rodent intermediate hosts and migrate from this site to
      the lung following ingestion of the intermediate host. During migration, several
      moults occur and instars encounter a variety of tissue barriers and environmental
      cues. It was therefore relevant to define the proteins and proteinases released
      by the different instars during this migration as they are likely to be essential
      for tissue penetration, feeding and immune evasion. In vitro released proteins
      (IVRP), commonly termed ES, were defined on the basis of molecular size and
      immune recognition by naturally infected rodent intermediate hosts. In addition,
      proteinases present in IVRP were characterized using gelatin-substrate gels and
      protein degradation assays. These studies showed that the protein profile is
      subtly different when IVRP from different instars is compared. In addition, IVRP
      from each instar contained metallo-proteinases with proteolysis at 48 kDa
      dominating in all stages. However, other higher molecular weight activities were,
      to an extent, released in a stage-specific manner. These proteinases degraded
      haemoglobin and fibrinogen as well as structural proteins such as collagen and
      fibronectin, suggesting roles in bloodmeal digestion and tissue penetration.
      Immunoglobulin digestion was not demonstrated.

PMID- 12003064
TI  - A model to explain the replacement of Schistosoma intercalatum by Schistosoma
      haematobium and the hybrid S. intercalatum x S. haematobium in areas of sympatry.
AB  - Numerous hypotheses have been postulated to explain the rapidly changing
      parasitological situation in Loum, Cameroon as a result of the interaction
      between Schistosoma haematobium and S. intercalatum. The aim of this study is to
      test the various hypotheses using a simple mathematical model, incorporating
      equal and unequal sex ratios of adult schistosomes, recombinations, and levels of
      compatibility with the intermediate molluscan hosts, B. forskalii and B.
      truncatus. The model assuming an equal sex ratio does not fit with the existing
      field data in that it predicts a continued presence of S. intercalatum, S.
      haematobium and the hybrids. The model assuming a sex bias in favour of males,
      which reflects the situation usually observed in schistosome populations,
      predicts the loss S. intercalatum which indeed concurs with the most recent data.

PMID- 12003065
TI  - Mesocestoides corti (syn. M. vogae): modulation of larval motility by
      neuropeptides, serotonin and acetylcholine.
AB  - The effect of platyhelminth FaRPs and selected classical neurotransmitters on the
      motility of intact Mesocestoides corti (syn. M. vogae) tetrathyridial larvae was
      studied in vitro using a micromotility meter. The effects of the test substances
      were temperature dependent and these were examined at 4, 23, 30 and 36 degrees C.
      At 36 degrees C all test substances had concentration-dependent excitatory
      effects, with thresholds for activity of: 100 nM (GNFFRFamide), 10 microm
      (YIRFamide), 30 microM (GYIRFamide), 100 nM (serotonin) and 100 microM
      (acetylcholine). At this temperature significant elevation of motility indices
      (MI) was recorded within 5 min of the addition of peptide or serotonin. The
      effect of acetylcholine was slower in onset and appeared 15-20 min post-addition.
      At 30 degrees C larval motility diminished more rapidly than that recorded at 36
      degrees C, following the addition of 1 mM of each test substance. At 23 degrees C
      only serotonin (1 mM) significantly increased the MI, all other test substances
      having no apparent effect. Larval movement was completely arrested at 4 degrees
      C. The results demonstrate for the first time excitatory effects of platyhelminth
      neuropeptides and acetylcholine on muscle systems in cestode larvae. The fact
      that the only known cestode FaRP, GNFFRF amide, was more potent than any of the
      turbellarian FaRPs tested, suggests structural conservation of FaRPs and FaRP
      receptors within the cestodes.

PMID- 12003066
TI  - Migration, site-specificity and development of Benedenia lutjani (Monogenea:
      Capsalidae) on the surface of its host, Lutjanus carponotatus (Pisces:
      Lutjanidae).
AB  - Life-history attributes of the capsalid monogenean Benedenia lutjani, a parasite
      of Lutjanus carponotatus from the Great Barrier Reef, Queensland, Australia, were
      investigated from experimental infections. Oncomiracidia of B. lutjani invaded
      and attached at any site on the fish, but more commonly invaded body surfaces.
      Immature specimens then migrated to the pelvic fins. Development of the
      reproductive organs of B. lutjani corresponded with migratory movements on the
      host. Parasite aggregation on the pelvic fins coincided with the development of
      functional male reproductive organs and some protandrous worms that possessed a
      vagina appeared to be inseminated. Migration to, and aggregation on, the
      branchiostegal membranes (membranous folds posterior to the opercula) coincided
      with the onset of sexual maturity and commencement of egg production by
      parasites. The rate of parasite development and the timing of migratory events on
      the host were influenced by water temperature. All specimens of B. lutjani
      reached sexual maturity between 12 and 14 days p.i. at 24 degrees C and between 8
      and 10 days p.i. at 27 degrees C. Anterior hamuli grew continually during a 16
      day experiment at 27 degrees C and 25-day experiment at 23 degrees C and their
      length appeared to provide a suitable index to estimate parasite age. The
      possible adaptive significance of the migratory behaviour, site-specificity and
      its link with changes in parasite development are discussed.

PMID- 12003067
TI  - Comparison of the macroparasite communities of wild and stocked brown trout
      (Salmo trutta L.) in the west of Ireland.
AB  - The aim of the present study was to compare the helminth infra and component
      communities of wild and stocked brown trout in Lough Feeagh, in the west of
      Ireland, and also to examine the establishment and development of helminth
      communities in stocked brown trout. Fish were sampled in May, August and November
      1997 and 1998 and an additional sample of wild brown trout was examined in April
      1997. In total 217 wild trout and 122 stocked trout were examined. The
      acanthocephalans Acanthocephalus clavula and Pomphorhynchus laevis were the first
      parasite species to infect stocked trout in May 1997. In May 1998 both
      acanthocephalan species along with the trout specialists Eubothrium crassum and
      Crepidostomumfarionis were the first to infect trout. Mean species richness
      values for stocked trout increased from May to November, in 1997 and 1998. For
      wild trout, mean species richness values increased from April to November, in
      1997 and decreased from May to November in 1998. The parasite communities of wild
      trout were richer than those of stocked trout in May of both years. In August the
      parasite communities recorded for wild and stocked trout were similar in terms of
      the number of species present but differed in terms of structure, and in November
      the parasite communities of stocked trout were richer than those of wild trout.

PMID- 12003068
TI  - Dietary pectin, but not cellulose, influences Heligmosomoides polygyrus
      (Nematoda) reproduction and intestinal morphology in the mouse.
AB  - Dietary texture has been reported to influence parasite establishment and
      survival, but to what degree this relationship is modified by either the type or
      quantity of dietary fibre is unknown. Using a 2 x 4 factorial design, we explored
      the relationship between fibre type (soluble pectin vs insoluble = cellulose) and
      fibre quantity (0, 5, 10 and 20% by dry weight) on parasitic outcomes in BALB/c
      mice infected with 100 Heligmosomoides polygyrus (Nematoda) larvae. Pectin, but
      not cellulose, exerted a significant effect on parasite egg production. Following
      in vitro culture of female worms, increasing levels of dietary pectin were
      associated with increasing release of eggs. Yet this pattern was not observed in
      vivo, where per capita egg production peaked at the 10% pectin concentration, but
      was very low in mice fed 20% pectin. Parasite establishment was elevated in mice
      fed 20% pectin, but was unaffected by cellulose concentration. Neither type nor
      quantity of fibre affected H. polygyrus survival or spatial distribution along
      the gastrointestinal tract. To what degree differences in parasite establishment
      and reproduction could be attributed to the marked effects of pectin on gut
      morphology (increased intestinal length, villus length, mucosa thickness and
      villus/crypt ratio) requires further exploration. Our data indicate that
      cellulose is preferable to pectin as the source of fibre for experimental diets
      as cellulose did not affect H. polygyrus establishment, reproduction or survival
      during a 4-week primary infection.

PMID- 12003069
TI  - The health state of the eel swimbladder as a measure of parasite pressure by
      Anguillicola crassus.
AB  - We have developed an index based on macroscopic criteria to easily assess the
      health state of the eel swimbladder as a result of infection by the nematode
      Anguillicola crassus. In the sampling area (brackish lagoons of the French
      Mediterranean coast), 92% of the host sample (1,251 eels covering all size
      classes) showed pathological signs of infection. The general trend was for
      increasing damage as eel size increased, thus suggesting accumulation of
      pathological effects. We also revealed a non-linear relationship between the
      swimbladder index and the abundance of living worms. In particular, we showed
      that severely damaged swimbladders harboured very few living nematodes. We argue
      that the swimbladder degenerative index more closely reflects the parasite
      pressure than does classic parasite count. We found seasonal variation in the
      swimbladder index, with maximum damage occurring in July and thereafter a trend
      for healthy individuals. We discuss the possibility that the seasonal decrease in
      the swimbladder index could reflect the death of the more severely affected
      individuals during the warmest months.

PMID- 12003070
TI  - To avoid or eliminate: cestode infections in copepods.
AB  - The outcome of a parasite infection is the result of the interaction between the
      host and the parasite. In the system we studied, there are 3 critical stages for
      the outcome of infection of the (intermediate) host, the copepod Macrocyclops
      albidus, with the cestode Schistocephalus solidus. During the establishment phase
      of the parasite, the host may firstly avoid ingesting the parasite and, secondly,
      may prevent the parasite from entering the body cavity and, thirdly, during the
      growth phase of the parasite, the host's immune system may eliminate the parasite
      from the body cavity. We were able to study the growth phase separately from the
      establishment phase. The establishment phase was influenced by characteristics of
      the host as well as characteristics of the parasites. Small copepods and males
      performed poorly; they were more often infected and had a lower survival.
      Parasites from different sib-groups differed in infectivity. During the growth
      phase some disappearance of parasites was observed. However, this could not be
      related to any of the studied characteristics of the host, and the sib-groups of
      parasites did not seem to differ in their likelihood to disappear. Instead, we
      suggest that disappearance of parasites, once they have entered the body cavity,
      may be due to intrinsic mortality of the parasites, independent of the host or
      the sib-group that the parasites belong to. This indicates that the crucial
      interactions between host and parasite determining the outcome of infection takes
      place in the short time-period between ingestion and penetration of the gut-wall.

PMID- 12003071
TI  - Assessment of biodegradable controlled release rod systems for pain relief
      applications.
AB  - Control of chronic, severe pain is a difficult and important clinical problem for
      most patients, especially those with cancer. Although current applications are
      insufficient for a satisfactory solution to this problem, the rate of disease
      incidence is increasing worldwide, thus making the problem more apparent. Based
      on this fact, this study was designed with the ultimate goal of formulating a
      controlled release system of pain relievers, mainly opioids, for the local
      treatment of pain to achieve satisfactory, fast, and less side effect-related
      relief and to provide a better life status for chronic pain patients. Two
      copolymers of a biodegradable polymer poly(L-lactide-co-glycolide) (PLGA) were
      used to prepare an implantable rod type drug release system containing either an
      analgesic or anesthetic type of pain reliever. In vitro drug release kinetics of
      these systems were studied. It was observed that release from PLGA 85 : 15 was
      more zero-order than it was from PLGA 50 : 50. A zero-order release rate was
      obtained for codeine, hydromorphone, and bupivacaine from PLGA (85 : 15) rods.
      They, however, were released from PLGA (50 : 50) rods with Higuchi kinetics. The
      drug solubility was also influential on release rate, as shown by the zero-order
      morphine release from PLGA (50 : 50) rods. Scanning electron micrographs (SEMs)
      of the monolithic rods revealed erosion of the rods and the removal of drug
      crystals from the rod structure.

PMID- 12003072
TI  - Platelet activation after in vitro contact with seven acrylic bone cements.
AB  - Seven acrylic bone cements were evaluated: Cemex Rx (Tecres S.p.a., Italy), Cemex
      Isoplastic (Tecres S.p.a., Italy), Zimmer Low Viscosity Cement (L.V.C., Zimmer,
      IN, USA), Zimmer bone cement - dough type (Zimmer, IN, USA), CMW (DePuy
      International Ltd., UK), Cerim LT (Cremascoli S.r.l., Italy), and Palacos (Merck,
      Wehreim, Germany). The cements after polymerization were put in contact in vitro
      with platelet-rich plasma. Plasma in contact only with siliconated glass was used
      as the negative control. After contact, platelet number, beta-thromboglobulin
      (beta-TG), and transforming growth factor-beta1 (TGF-beta1) were determined. The
      Wilcoxon signed rank test showed Palacos R and L.V.C. induced a significant
      decrease of platelet number compared with the negative control. All cements
      determined a significant increase in beta-TG. CMW 3, Palacos, L.V.C., and Zimmer
      dough type determined a significant increase in TGF-beta1 compared with the
      negative control.

PMID- 12003073
TI  - The effect of cyclic swelling (octamethylcyclotetrasiloxane) on the physical
      properties of silicone breast implant shells.
AB  - Changes in the physical and mechanical properties of silica filled silicone
      elastomeric films were studied as a function of repeated sorption extraction
      cycling. The sorption of octamethylcyclotetrasiloxane (D4) on the properties of
      three silicone filled elastomeric films was analyzed. Two of the films, SILASTIC
      I and SILASTIC II, were shells of explanted breast implants and the third, a
      calendered film, prepared with similar composition to the elastomer used for the
      breast prosthesis were studied. The as-received (AR) SILASTIC I and II films
      contained 20 and 26.5 wt% non-cross-linked material that was removed by
      extraction with hexane. The failure properties of the extracted films are
      significantly higher than those of the AR films. The amount of swelling, weight
      gain, volumetric change, and the stress- and strain-to-fail of the films were
      measured in the as-received condition, and after a series of extractions and
      swellings. Repeated cycling (up to 5 cycles) of extraction-swelling had
      essentially no effect on the failure properties of films when all the diluent was
      removed. The effect of diluent on the failure properties of all three films was
      quite large. The stress-to fail of the swollen film was reduced a factor of 6
      compared to baseline extracted samples while the corresponding strain values were
      reduced a factor of 5. The energy to fail of the swollen compared to baseline
      films was reduced almost a factor of 50. However, the overall mechanical
      properties of the films are restored when the diluent was removed. The mechanical
      forces involved in the swelling process do not degrade the polymer even when
      cycled through five swell-extract cycles.

PMID- 12003074
TI  - Swelling behavior of hyaluronic acid and type II collagen hydrogels prepared by
      using conventional crosslinking and subsequent additional polymer interactions.
AB  - Polymer-polymer interactions, such as hydrophobic and electrostatic interactions,
      were introduced into covalently crosslinked composite matrices consisting of an
      anionic polysaccharide, hyaluronic acid (HyA) and a cationic polypeptide, type II
      collagen. The matrices were covalently crosslinked using a water soluble
      carbodiimide (WSC; 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride)
      and were immersed at different temperatures in excess water or 0.4 M NaCl aqueous
      solution, i.e. the optimal salt concentration to suppress polyion complex
      formation. Hydrophobic interaction was introduced in the matrices when the
      temperature was increased. Matrices with polymer-polymer interactions could be
      obtained when immersed in water at 37 degrees C without any collagen
      denaturation. The molar ratios of [OH]/[COOH] and [NH2]/[COOH], and WSC
      concentration in precursor solutions of HyA-collagen composite matrices
      influenced the electrostatic interactions. The hydrophobic and electrostatic
      interactions in the matrix were maintained in water, even at low temperatures,
      while in salt solutions at elevated temperatures, these interactions were
      nullified.

PMID- 12003075
TI  - Modulation of osteoblast function using poly(D,L-lactic acid) surfaces modified
      with alkylation derivative of chitosan.
AB  - Poly(D,L-lactic acid) (PDLLA) was modified with alkylated chitosan (N-butyl
      chitosan and N-cetyl chitosan), and the effects of modified films on the
      functions of rat osteoblasts were investigated. The characteristics of surfaces
      (both modified and control) were examined by water contact angle measurement and
      electron spectroscopy for chemical analysis (ESCA). Cell morphologies on these
      surfaces were taken using scanning electron microscopy (SEM). Cell attachment and
      proliferation were used to assess cell behavior on modified surface and control.
      MTT assay was used to determined cell viability, and alkaline phosphatase (ALP)
      activity was taken to evaluate differentiated cell function. Compared with the
      untreated films, no significant difference in cell attachment of osteoblasts was
      found on the modified films at a period of 8 h (p > 0.05). However, cell
      proliferation of N-butyl chitosan rather than N-cetyl chitosan modified PDLLA
      films was significantly higher than that found on control one (p < 0.05) at the
      end of the 4th and 7th days. The cell viability of osteoblasts on N-butyl
      chitosan modified PDLLA films were found higher than that on control (p < 0.05).
      These results suggested that N-butyl chitosan contributed greater than N-cetyl
      chitosan when used to modify PDLLA films for improving its biocompatibility.

PMID- 12003076
TI  - Synthesis and characterization of poly(DL-lactide)-grafted gelatins as
      bioabsorbable amphiphilic polymers.
AB  - A series of poly(DL-lactide) grafted gelatins, as new bioabsorbable amphiphilic
      polymers useful in parenteral drug delivery systems and in tissue engineering,
      were synthesized by the ring opening polymerization of DL-lactide onto a
      fractionated gelatin with the molecular weight of 1.02 x 10(5). Using tin(II)
      bis(2-ethylhexanoate) as catalyst, the bulk copolymerization at 140 degrees C and
      solution copolymerization in dimethylsulfoxide (DMSO) at 80 degrees C were
      firstly performed in the presence of gelatin. The results showed that the
      solution copolymerization in DMSO could afford the expected copolymers but the
      bulk copolymerization would result in an insoluble crosslinked product. The
      number of grafting sites on gelatin chain could be adjusted by the partial
      trimethylsilylation of side hydroxy, amino and carboxylic groups in gelatin. The
      solution copolymerization of DL-lactide on the partially protected gelatin in
      DMSO was also successful in providing copolymers with different molecular
      weights. The synthesized copolymers were characterized on the basis of elemental
      analysis, IR, 1H-NMR and thermal analysis. The IR and 1H-NMR data of these
      produced copolymers suggested that polylactide branches could be grafted onto
      gelatin via the side groups such as hydroxyl and amino groups in the solution
      copolymerization as well as carboxylic groups in bulk copolymerization. The
      molecular weights of the copolymers could be calculated from the difference of
      nitrogen contents between a copolymer and free gelatin. The results indicated
      that molecular weight of the copolymers and those of polylactide branches were
      increased with the feeding ratio of DL-lactide to gelatin in the
      copolymerization. However, because of the steric hindrance of some grafting sites
      on gelatin and the transesterifications of the propagating polylactide branches
      on gelatin with possibly formed homo-polymeric polylactide chains, the finally
      formed polylactide branches on gelatin were not very large and the highest
      average molecular weight of a polylactide branch was not over 4500 in any
      solution copolymerizations. The results from the thermal analysis of some
      copolymers, including thermogravimetry and differential scanning calorimetry,
      showed that the absorbed water in the samples could be lost at a temperature
      range below 150 degrees C and melting point decreased with increase of
      polylactide branches in the poly(DL-lactide)-grafted gelatins.

PMID- 12003077
TI  - Pull-out mechanical measurement of tissue-substrate adhesive strength:
      endothelial cell monolayer sheet formed on a thermoresponsive gelatin layer.
AB  - Although adhesive strength of a single cell on substrates has been reported, the
      adhesive strength at the tissue-substrate interface has not been reported.
      However, the tissue-substrate adhesive strength must provide important criteria
      for performance of implant devices. This article deals with the tissue-substrate
      adhesive strength for fully endothelialized tissue, which was formed on
      commercial tissue culture dishes with or without a coating layer of
      thermoresponsive gelatin (poly(N-isopropylacrylamide)-grafted gelatin, which
      dissolves in water at room temperature but is precipitated at 37 degrees C). To
      determine tissue-substrate adhesive strength, a pull-out technique using a glue
      coated cover glass was used. The adhesive strength of monolayered tissue on a
      noncoated dish was approximately 560 Pa or 230 nN/cell at 37 degrees C. For
      dishes coated with thermoresponsive gelatin, the adhesive strengths were 1050 Pa
      or 584 nN/cell at 37 degrees C, and 26 Pa or 14 nN/cell at room temperature. For
      noncoated dishes, delamination occurred mostly at the interface between the
      extracellular matrix (ECM) secreted by the cells and the dish surface; and for
      coated dishes, it took place fully at the interface between ECM and the dish
      surface. This technique enables determination of the adhesive strength between a
      full monolayered tissue and a substrate.

PMID- 12003078
TI  - Kinetics of poly(propylene fumarate) synthesis by step polymerization of diethyl
      fumarate and propylene glycol using zinc chloride as a catalyst.
AB  - Diethyl fumarate and propylene glycol were reacted in the presence of a zinc
      chloride catalyst to synthesize poly(propylene fumarate) (PPF) over a period of
      12 hours. The kinetics of the transesterification polymerization at 130 degrees
      C, 150 degrees C, and 200 degrees C were determined by gel permeation
      chromatography (GPC) analysis. The initial rate of polymerization at each
      temperature was quantified by calculating the rate of change of the number
      average molecular weight (Mn). At 200 degrees C, gelation of the PPF occurred
      after 4 h. GPC analysis of the reaction showed that PPF synthesized at 150
      degrees C had a higher final Mn of 4600 (+/- 190) and a higher weight average
      molecular weight of 10500 (+/- 760) than at 130 degrees C (n = 3). The chemical
      structure of the PPF was verified by NMR and FT-IR analysis. This study
      demonstrated that the maximum Mn of PPF by a transesterification reaction is
      limited due to gelation of PPF at high temperature.

PMID- 12003079
TI  - The global perspective of the health inequality arising from inadequate maternal
      and neo-natal nutrition.

PMID- 12003080
TI  - The emerging importance of dietary lipids, quantity and quality, in the global
      disease burden: the potential of aquatic resources.
AB  - Achievement of Health-for-All, whereby people everywhere throughout their lives,
      have the opportunity to reach and maintain the highest attainable level of health
      is impossible whilst hunger, starvation, and malnutrition remain. Malnutrition
      covers a broad spectrum of ills, including undernutrition, specific nutrient
      deficiencies, and overnutrition; and it kills, maims, retards, cripples, blinds,
      and impairs human development on a truly massive scale worldwide. In the
      developing world in 1995, of the estimated 10.4 million deaths among children
      under 5 years of age, protein-energy malnutrition was an associated and causative
      factor in 5.1 million of these deaths (i.e. 49%). On the other hand, evidence has
      recently been compiled suggesting that of the more than 10 million cases of
      cancer that occurred in 1996, an estimated 30-40% (3-4 million every year) are
      preventable by feasible, appropriate diets, and by physical activity and
      maintenance of appropriate body weight. Malnutrition affects all age groups
      across the entire lifespan. From the moment of conception, throughout foetal
      life, iodine, folate and intrauterine nutrition have a profound influence on
      development, growth, morbidity, mortality, not only in utero and in early
      infancy, but on morbidity, physical and mental capacity throughout life. Despite
      significant improvements in world food supplies, health conditions, and
      availability of educational and social services, no population escapes
      malnutrition's grasp. All countries have significant population groups with some
      form of debilitating malnutrition. Malnutrition worldwide, includes a spectrum of
      nutrient-related disorders, deficiencies and conditions including the following
      major public health problems; Intrauterine growth retardation, protein-energy
      malnutrition, Iodine deficiency disorders, Vitamin A Deficiency, Iron Deficiency
      Anaemia and Overweight and Obesity (WHO, Website).

PMID- 12003081
TI  - The effect of intrauterine growth restriction on the development and health of
      children.
AB  - The neurodevelopmental and cognitive outcome of long-term Intrauterine Growth
      Restriction (IUGR) has been followed up from pregnancy to school age at the Tel
      Aviv Child Development Centre.

PMID- 12003082
TI  - A re-evaluation of methods for measuring the health and development of children.

PMID- 12003083
TI  - Cognitive and visual development: influence of differences in breast and formula
      fed infants.
AB  - Several recent studies document a beneficial effect of breast-feeding on later
      neurodevelopmental outcomes. The mechanisms involved are still in need of
      elucidation, but evidence is accruing that the fatty acid (FA) composition of
      human milk plays a role. The composition of body fats, from circulating
      erythrocyte lipids to brain phospholipids, is linked in infants to the early
      feeding mode and which FA predominates among circulating lipids influences visual
      and neurodevelopmental performance test scores. In these studies, greater
      differences were found between breast-fed and standard formula-fed infants, the
      latter showing low tissue long-chain polyunsaturated fatty acids (LCPUFA:
      arachidonic acid, AA, 20:4n-6; eicosapentaenoic acid, EPA, 20:5n-3;
      docosahexaenoic acid, DHA, 22:6n-3) accretion and lower visual and
      neurodevelopmental test scores. Human milk contains LCPUFA, while most available
      formulas, especially those intended for full-term infants, do not. With the
      progressive introduction of solid foods, the question arises whether a specific
      or "ideal" dietary lipid mixture can be found to meet growth requirements and
      ensure a lipid balance adequate for the early and effective preventive purposes.
      These complementary aspects are challenges for the paediatric nutrition
      researcher today.

PMID- 12003084
TI  - Behavioural development and mental health in infancy: object retrieval.
AB  - In order to assess poor mental development, we must be aware of the normal
      development against which to measure up what is supposed to be delayed, deviant
      or malfunctioning. Experimental Child Psychology has traced parameters of the
      developing cognitive system of the infant which are important factors that
      influence the configuration of a normally balanced, or equilibrated, composition
      of intelligence in later life. The Developmental Neuroscience approach gives a
      scientific explanation to what parents might experience as unresponsiveness, lack
      of distress and rage control, or excessive clinging of a demanding child.

PMID- 12003085
TI  - Embryonic immune development and risks of HIV infection.
AB  - The importance of the maternal immune system, during both gestation and
      breastfeeding, for the health of future generations is discussed.

PMID- 12003086
TI  - Intrauterine vascular development: programming effects of nutrition on vascular
      function in the new born and adult.
AB  - The importance of the Barker hypothesis, relating faulty maternal nutrition to
      low birth weight and subsequent disease in adult life, is examined in relation to
      vascular function.

PMID- 12003087
TI  - Maternal malnutrition in the UK and low birthweight.

PMID- 12003088
TI  - Docosahexaenoic acid sources for the developing brain during intrauterine life.
AB  - Docosahexaenoic acid (DHA, 22: 6n-3) and arachidonic acid (AA, 20: 4n-6)
      provision to the developing fetus, with emphasis towards brain and vascular
      system growth, is a subject of increasing concern particularly under pathological
      conditions associated with premature birth or in utero growth restriction
      following obstruction of the maternal-fetal blood flow. Most of DHA, but also AA
      accretion under physiological conditions, is maternally dependent and requires
      adequate maternal nutrition and normally functioning placental-fetal circulation.
      It has been demonstrated that unlike other fatty acids (FA), DHA is
      preferentially transported across the placenta into the fetal circulation. The
      selective transplacental DHA transfer is probably mediated by specific carrier
      proteins. While some of the latter may be acting in fetal organs, the
      mechanism(s) for the selective accumulation of DHA in brain is still unknown. The
      fetal brain and also the fetal liver are capable of producing DHA from linolenic
      (LnA, 18:3 n-3) acid. How effective this local elongation-desaturation mechanism
      for DHA provision is and to what degree this route is activated in premature
      births is not clear. Transfer of DHA via the fetal gastrointestinal tract is an
      additional route to provide DHA to other fetal organs. As indicated by animal
      model studies, it holds the potential for DHA supply when the maternal pathway is
      compromised.

PMID- 12003089
TI  - Are there long term protective effects of breast feeding against later obesity?

PMID- 12003090
TI  - Vitamin A during pregnancy.
AB  - Vitamin A is an essential micronutrient throughout life. In areas of developing
      countries where vitamin A deficiency is endemic, an estimated 40% of the children
      are likely to be sub clinically deficient of the vitamin. Yet, the traditional
      view that preschool age children represent the main population at risk of vitamin
      A deficiency has been replaced by the growing awareness that sub clinical and
      even clinical vitamin A deficiency also occurs in women of reproductive age and
      infants less than 6 month of age. During the period of early foetal development
      the supply of vitamin A must be carefully managed to ensure that the developing
      foetus is exposed to neither too little not too much vitamin A because either
      condition can have teratogenic consequences. Towards the end of gestation,
      adequate maternal vitamin A status and dietary intakes are important to maximize
      the vitamin A transferred to the foetus in preparation for parturition and
      lactation. A review of the current knowledge and prospects for future research is
      presented.

PMID- 12003091
TI  - Maternal diabetes and its cell membrane abnormalities as they affect the foetus:
      implications for the mother and birth defects.
AB  - My brief is to discuss maternal diabetes and its implications for birth defects.
      The perinatal mortality in Britain has fallen in the last 70 years from 60 per
      1000 live births to less than 10. For the baby of the diabetic mother there has
      been a more dramatic decrease from 249 per thousand live births reported by Peel
      and Oakley in 1949 to approximately 30 in the Swedish cohort in 1993. However
      even in countries such as Sweden with one of the lowest figures there is still a
      three fold higher perinatal mortality for the baby of the diabetic mother
      compared with the background population. There has been a much less dramatic
      decrease in the incidence of congenital malformations. Peel and Oakley reported
      an incidence of 6.9% in 1949, and Hanson from Sweden in 1993 reported only a
      marginally lower incidence of 6.1%. Recent observations indicate that gestational
      diabetes (GDM) may be associated with increased incidence of fetal malformation
      and perinatal mortality. The most frequent and significant morbidity is fetal
      macrosomia, which in turn is associated with increased risk of birth injuries and
      asphyxia, (Persson and Hanson. 1998). Detection and definition of congenital
      malformation vary but in spite of this and the much better maternal diabetic
      control, congenital malformation today forms a major cause of the perinatal
      morbidity and mortality.

PMID- 12003092
TI  - Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure
      on circulatory adaptation in preterm infants.
AB  - We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine
      treatments on the autonomic cardiovascular control in preterm neonates with
      respiratory distress syndrome during the first 2 days of life. Serial
      measurements of heart rate (HR), blood pressure (BP) and respirogram were
      performed during the first 2 days of life in 28 preterm infants below 33 weeks of
      gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in
      12 nonexposed preterm controls. Spectral analysis was used for the quantification
      of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR
      or the systolic, diastolic or mean BP, it was associated with significant
      decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no
      consistent effects on the autonomic cardiovascular control during the first 2
      days of life. Our data suggest that maternal MgSO4 treatment decreases the
      neonatal high frequency changes in BP. This early vascular stabilizing effect of
      antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular
      catastrophes, in the vulnerable areas of the brain, among the preterm infants
      with respiratory distress syndrome.

PMID- 12003093
TI  - Post-occlusion brachial artery vasodilatation after ischaemic handgrip exercise
      is nitric oxide mediated.
AB  - Flow-mediated vasodilatation (FMD) of the brachial artery is used as a measure to
      quantify endothelial dysfunction. However, FMD after occlusion only is small in
      healthy people over middle age, but can be increased after handgrip exercise. The
      aim of this study was to evaluate whether postocclusion vasodilatation after
      handgrip exercise is mediated by nitric oxide (NO). High frequency ultrasound was
      used to measure brachial artery diameter at rest and after reactive hyperaemia
      with and without handgrip exercise during NaCl or NG-monomethyl-L-arginine (L
      NMMA) infusion in healthy 60-year-old men. Postocclusion vasodilation was
      significantly larger after handgrip exercise compared with occlusion only
      (P=0.0078). Postocclusion vasodilatation was significantly lower after ischaemic
      handgrip exercise during intra-arterial infusion of L-NMMA compared with infusion
      of NaCl (P = 0.039). It may be concluded that the increased postocclusion
      brachial artery vasodilatation observed after ischaemic handgrip exercise is at
      least partly NO mediated. This modification of the investigation procedure may
      improve our ability to quantify FMD in subjects with and without vascular
      disease.

PMID- 12003094
TI  - Taichiquan acutely increases heart rate variability.
AB  - A group of 15 elderly men and 14 young male students of physical education made
      twice a series of Taichiquan (TCQ) practices. Their electrocardiograms were
      recorded on tape-recorder and heart rates and heart rate variability (HRV) were
      calculated from digitized data. Here we report the results of recordings in
      supine positions before and after the first and second series of TCQ. Intervals
      between heart beats (RRIs) and their standard deviation (SDNN) increased in older
      men from recordings before the exercise to postexercise. In young subjects the
      SDNN and total variance (TV) of RRIs increased. HRV increases immediately after
      TCQ-exercise in young and old male healthy subjects. Whether these practices have
      permanent effects and effects in patients need controlled and prospective
      studies.

PMID- 12003095
TI  - Surface activity of tear fluid in patients with primary Sjogren's syndrome.
AB  - Rupture of the preocular tear film leads to formation of a dry spot on the cornea
      with ocular irritation and symptoms of dry eye. One of the factors determining
      the stability of the tear film is its surface activity. The purpose of this study
      was to examine the surface activity of tear fluid from patients with Sjogren's
      syndrome. Tear fluid was sampled from the eyes of 16 patients with primary
      Sjogren's syndrome. The surface activity of the sample was measured on a Wilhelmy
      balance. Maximum and minimum surface tension was 72.2+/-1.7 and 52.9+/-7.4 mN m(
      1), respectively. Corresponding values in a previously studied group of normal
      subjects were 71.5+/-1.3 and 46.6+/-3.8 mN m(-1), respectively. The difference in
      minimal surface tension was statistically significant (P<0.001). Reduced surface
      activity may be caused by dysfunction of the Meibomian glands and suggests a
      mechanism for causing the symptoms of dry eyes.

PMID- 12003096
TI  - Loss of size-selectivity at histamine-induced exudation of plasma proteins in
      atopic nasal airways.
AB  - Plasma proteins occur in the airway lumen in inflammatory airway diseases. This
      study tests the hypothesis that airway microvascular-epithelial exudation of
      plasma proteins, as induced by a non-injurious inflammatory mediator, is
      characterized by loss of size-selectivity. Using a nasal pool-device, the nasal
      mucosa of 10 allergic individuals, without current disease, was sequentially
      exposed to saline and histamine (40 and 400 microg ml(-1)). Nasal lavage fluid
      and blood-levels of albumin (69 kD) and alpha2-macroglobulin (720 kD) were
      determined. Histamine produced concentration-dependent exudation of albumin and
      alpha2-macroglobulin. The albumin/alpha2-macroglobulin concentration ratio of the
      saline lavage fluid (baseline) was 40+/-19. However, at the histamine challenges
      the ratios were 25+/-3 and 22+/-2, respectively, which did not differ from that
      of circulating plasma (22+/-2). We conclude that there is minor and size
      selective luminal entry of plasma proteins at baseline. However, at concentration
      dependent exudative responses to histamine, plasma proteins enter the airway
      lumen without being sieved. These data indicate that inflammatory stimulus
      induced extravasation, lamina propria distribution and paracellular epithelial
      passage of plasma occur with minimal size-selectivity. Inferentially, the full
      immunological capacity of plasma proteins may readily be made available at the
      surface of human intact airway mucosa.

PMID- 12003097
TI  - Effects of central sympathetic inhibition on heart rate variability during steady
      state exercise in healthy humans.
AB  - The profound reduction in heart rate variability (HRV) that occurs during
      exercise is thought to be, at least in part, the result of sympathetic nervous
      system activation. Moxonidine is a centrally acting anti-sympathetic drug, which
      suppresses sympathetic nervous system outflow by stimulation of central
      imidazoline receptors located in the rostral ventro-lateral medulla. This study
      was designed to investigate the combined effects of central sympathetic
      inhibition with moxonidine and steady-dynamic exercise on HRV. Ten normal males
      participated in a double-blind cross-over study, taking either placebo or 0.4 mg
      of moxonidine. The subjects were studied at rest and during steady-state
      exercise. HRV was measured considering both time and frequency domain parameters.
      As a non-linear measure, the Poincare scatter-plot was measured and analysed
      quantitatively. Ventilation and gas exchange were also measured during exercise.
      In addition, plasma catecholamines were measured at rest and during exercise. The
      only parameter changed, at rest, by moxonidine was the blood pressure which was
      reduced. During exercise, moxonidine reduced plasma noradrenaline (NA), compared
      with the placebo (P<0.01). The only change observed in HRV during exercise was a
      significant reduction of the continuous long-term standard deviation (SD2) of the
      Poincare scatter-plot of the R-R interval (P<0.05). However, the potential and
      prognostic significance of this result needs to be further assessed.

PMID- 12003098
TI  - Enhanced efficacy of porcine lung surfactant extract by utilization of its
      aqueous swelling dynamics.
AB  - This study investigates the interactions between a porcine lung surfactant (PLS)
      extract and distilled water, saline solution or Ringer solution. The phases which
      coexist in equilibrium with water or electrolyte solutions were analysed by X-ray
      diffraction and cryo transmission electron microscopy (cryo-TEM). A lamellar
      phase with a structure unit consisting of double bilayers was observed in water,
      whereas lamellar phases with the usual bilayer structure unit were formed in
      saline and in Ringer solutions. At 25 degrees C the presence of a 4.2-A peak in
      the X-ray diffraction wide-angle region of these three maximally swollen phases
      showed that most of the hydrocarbon chains were organized in a crystalline
      packing. At 42 degrees C the chains in all three phases were melted which, in
      combination with the low-angle diffraction, shows that they were liquid
      crystalline. Polyhedral-like vesicles and spherically shaped multilamellar
      vesicles were observed in cryo-TEM. The bilayer unit structures were consistent
      with the periodicity seen by X-ray diffraction. The dynamic swelling behaviour
      was followed in the polarizing microscope. A remarkable growth of birefringent
      networks was seen at the air interface of samples swollen in Ringer solution and
      saline solution. No such interfacial growth phenomena were observed during
      swelling in water without electrolytes. Then, these dynamics were analysed in
      relation to time-dependent pulmonary administration of the surfactant extract in
      rats. Variation in the time of administration (20 and 60 min) after mixing the
      extract with saline or Ringer solution showed clear differences in physiological
      effects. At pulmonary administration when the swelling behaviour in vitro showed
      a maximum in dynamics, the arterial oxygenation was superior to that of
      administration at a time after a steady-state had been reached. This means that
      the clinical performance of mammalian lung surfactant extracts can be
      significantly improved by taking the time-dependent aqueous swelling of the
      extract into account.

PMID- 12003099
TI  - Impact of ambulatory blood pressure monitoring on daily activity.
AB  - We evaluated the impact of wearing an ambulatory blood pressure (ABP) monitor on
      the usual daily activity of 16 healthy men and women. Daily ABP and heart rate
      (HR) were recorded on 2 days using the DynaPulse 5000 A system. Daily HR and
      activity were recorded on two further days using a dedicated HR monitoring
      system. All four sets of measurements were made for 8 h during which time the
      volunteers kept a simultaneous diary record of their physical activity. There was
      no detectable difference in physical activity records on any day. Mean daily HR
      was lower during ABP monitoring than during the dedicated HR monitoring carried
      out on different occasions (73+/-7 versus 81+/-7 beats min(-1), P<0.001). The
      lower mean HR observed during ABP monitoring compared with dedicated HR
      monitoring may reflect subtle differences in the physical behaviour of subjects
      being monitored, which could not be detected from the diary records.

PMID- 12003100
TI  - Neurovascular responses to sequential deep inspirations assessed via laser
      Doppler perfusion changes in dorsal finger skin.
AB  - A vasomotor reflex triggered by a rapid and deep inspiration causes arteriolar
      vasoconstriction and a transient decrease in skin blood flow in most people. This
      is the inspiratory gasp vascular response (IGVR). The most common site of its
      measurement has been on the palmar or plantar aspect of the digits and little is
      known about its features in skin with few or any arterial venous anastomoses
      (AVAs). A basic aspect of this response that has not been systematically studied
      is its associated with multiple sequential inspiratory gasps (IG) in the same
      person. Such information would provide insight as to whether there is any form of
      adaptation or temporal dependence and may serve as a basis for judging response
      variability. Thus, the present study was undertaken to characterize the normal
      pattern of responses in finger dorsum skin in a group of 28 normal persons who
      performed 21 sequential, uniformly spaced IG, over an interval of 42 min. The
      results show that IGVR measured on the finger dorsum have a magnitude comparable
      with that obtained on finger pulp, in spite of the relative dearth of
      sympathetically controlled AVAs on the dorsum. It was also found that the
      magnitude of the IGVR displays little if any tendency for sequential adaptation
      or temporal trending. Finally, the results indicate that the largest component of
      response variability is associated with subject-to-subject differences as
      compared with sequential variability within subjects.

PMID- 12003101
TI  - Absorption across the nasal airway mucosa in house dust mite perennial allergic
      rhinitis.
AB  - House dust mite allergens express protease activity and it has been suggested
      that this property has pathogenic effects by increasing airway absorption. In
      accordance, house dust mite allergens may increase mucosal permeability in vitro.
      The objective of the present study was to examine nasal absorption of
      desmopressin (1-deamino-8-D-arginine vasopressin) in patients with perennial
      house dust mite allergic rhinitis and in healthy subjects in vivo. Patients with
      perennial allergic rhinitis were examined after a 4-week treatment withdrawal
      period, when symptoms of allergic rhinitis occurred, and healthy subjects were
      examined together with the patients. Desmopressin (20 microg ml(-1)) was moved
      into the nasal cavity using a nasal pool-device that contained 15 ml fluid. The
      fluid was kept in the nasal cavity for 15 min and then recovered. Urine was
      collected for 24 h after the nasal administration and the urinary excretion of
      desmopressin was determined as an index of nasal absorption. The urinary
      excretion of desmopressin was 1148+/-535 pmol 24 h(-1) in patients with perennial
      house dust mite allergic rhinitis and 1012+/-291 pmol 24 h(-1) in healthy
      subjects. We conclude that nasal airway absorption of the 1067 Da peptide
      desmopressin is unaffected in perennial house dust mite allergic rhinitis
      compared with healthy subjects.

PMID- 12003102
TI  - Odds ratios for hip- and lower forearm fracture using peripheral bone
      densitometry; a case-control study of postmenopausal women.
AB  - BACKGROUND: Dual-energy X-ray absorptiometry (DXA) measured at the lumbar spine
      and particularly at the hip remain the gold-standard for diagnosing osteoporosis.
      However, devices for assessing the peripheral skeleton present several advantages
      in terms of lower price and portability. A major concern when using peripheral
      densitometry is the poor correlation with the central measurements. The main aim
      of this study is, therefore, to assess the possibility of expressing ultrasound
      measurements at the heel and bone mineral density (BMD) measured at the distal
      forearm as fracture odds ratios rather than an absolute measure of bone mass.
      METHODS: A total of 76 women with lower forearm fracture, 47 women with hip
      fracture and 231 age-matched women (controls) were included. All had broadband
      ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel using
      the DTU-one ultrasound scanner as well as BMD measured by dual X-ray
      absorptiometry on the DTX-200 at the distal forearm. RESULTS: BUA, SOS and BMD at
      the distal forearm were all significantly lower in fracture patients compared
      with their respective control groups. The odds ratio for lower forearm fracture
      was 3.1 (95% CI: 1.8; 5.2) for heel-BUA (T-score cutoff: -2.3), 4.1 (2.3; 7.4)
      for heel-SOS (-2.1) and 2.2 (1.3; 3.7) for lower forearm BMD (-2.7). The odds
      ratio for hip fracture was 3.4 (1.5-7.7) for heel-BUA (-2.7), 3.6 (1.6; 8.1) for
      heel-SOS (-2.6) and 3.2 (1.4; 7.4) for lower forearm BMD (-2.9). CONCLUSION:
      Peripheral densitometry can discriminate between hip- and lower forearm fracture
      patients and age-matched controls. Significantly elevated odds ratios for
      incurring these fractures can be calculated using device- and site specific t
      score cutoff values. The results from this case-control study need to be
      confirmed by prospective cohort studies.

PMID- 12003103
TI  - Determinants of respiratory system input impedance and bronchodilator response in
      healthy Finnish preschool children.
AB  - In order to study the determinants of respiratory system impedance and
      bronchodilator response in preschool children, a sample (n = 109) of healthy
      children (age 2.1-7.0 years) attending kindergarten was measured by using the
      impulse oscillometry. Their selection was based on a standardized questionnaire,
      negative skin prick test results and clinical examination, and sufficient
      cooperation. Triple measurements of respiratory resistance (Rrs) and reactance
      (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs), the resonance
      frequency (Fr) and the frequency dependence of resistance (dRrs/df) were
      performed, to determine individual mean values. Measurements were repeated after
      inhalation of 300 microg salbutamol (n = 89) or placebo (n = 19). At the
      baseline, Zrs and Rrs5-20 showed negative, and Xrs5-20, Fr and dRrs/df positive
      correlations with age, height and weight. However, logarithmic transformed height
      was the best independent variable for the regression equations of all the
      oscillometric variables. After inhalation of placebo, none of the oscillometric
      variables changed significantly. In the salbutamol group, the mean (SD) change in
      Rrs5 was -0.187 (0.124) kPa l(-1) s(-1) and -19.2 (10.2)%, corresponding to a
      lower reference limit of -36.9%. Both the within-test and between-test
      repeatabilities for the measurement of respiratory resistance were acceptable,
      for Rrs5 the coefficients of variation being 6.2 and 6.1%, respectively. As the
      overall success rate in our sample was high (89%), the forced oscillation
      technique seems to be a useful method in assessing respiratory function and
      bronchial lability in preschool children.

PMID- 12003104
TI  - Are soft tissue composition of bone and non-bone pixels in spinal bone mineral
      measurements by DXA similar? Impact of weight loss.
AB  - Weight loss seems associated with a decrease in bone mineral density (BMD) as
      measured by absorptiometry, which may be the result of accuracy errors caused by
      differences in soft tissue between non-bone and bone pixels. The aim was to study
      the abdominal fat% and thickness in regions corresponding to non-bone, soft
      tissue-only and bone pixels for spinal BMD measurements by dual energy X-ray
      absorptiometry (DXA), and to calculate the theoretical errors in measurement of
      changes in BMD by DXA as a result of changes in soft tissue heterogeneity with
      weight loss. Abdominal computed tomography (CT) and DXA scans were performed in
      34 obese subjects (42.1+/-10.1 years (mean +/- SD), wt: 102.1+/-12.8 kg and BMI:
      36.6+/-3.8 kg m(-2)) before and after weight loss (11.3+/-6.9 kg after 1 year).
      There were some significant differences in fat% and thickness of soft tissue
      between abdominal regions corresponding to non-bone and bone pixels,
      respectively, for spinal BMD measurements by DXA, both before and after weight
      loss. With weight loss there were some changes in the soft tissue heterogeneity,
      which caused a minor theoretical error (apparent, but false decrease of 1-2%) of
      borderline significance for the anterior-posterior (AP) spinal BMD by DXA.

PMID- 12003105
TI  - Oxygen desaturation during oesophageal manometry.
AB  - Eighteen generally fit clinical patients were monitored with pulse oximetry. Mean
      oxygen saturation levels were lower (P<0.05) during oesophageal manometry (97.7
      97.3%) than before it (98.3%). Fourteen out of seventeen (successful) traces had
      short 4-8% desaturation episodes, and in worst cases there were 8-9 episodes. It
      seems, therefore, that even patients with no predisposing factors than perhaps
      smoking and mild bronchial asthma are vulnerable to some oxygen desaturation in
      oesophageal manometry.

PMID- 12003106
TI  - Evidence for electrical remodelling of the atrial myocardium in patients with
      atrial fibrillation. A study using the monophasic action potential recording
      technique.
AB  - Experimental studies have shown that remodelling of the atrial myocardium is
      linked to the occurrence and perpetuation of atrial fibrillation (AF). Clinical
      evidence, however, is insufficient. We recorded monophasic action potentials
      (MAP) during AF from one to three sites in the right atrium in seven patients
      with chronic AF (CAF) and in 11 patients with paroxysmal AF (PAF). The
      fibrillatory (FF) interval between two consecutive upstrokes of the MAP was
      measured using a computer-assisted manual method. The mean, median, 15th, 10th,
      5th percentile and shortest FF intervals were calculated in each patient and used
      as estimates of the local atrial effective refractory period (AERP) during AF. In
      three patients burst pacing at 400 and 500 beats min(-1) was delivered during the
      MAP recording. In nine patients, the AERP was also tested using the extra
      stimulus technique during sinus rhythm. RESULTS: Thirty-eight recordings were
      obtained. The shortest FF interval was significantly shorter in patients with CAF
      as compared with that in patients with PAF (50+/-13 vs. 72+/-31 ms, P<005).
      Similar differences were seen in the mean, median, 15th, 10th, and 5th percentile
      FF interval. The AERP during sinusrhythm was significantly longer than the
      estimated AERPs (P<0 05 to P<0.01) in the nine patients. There was no significant
      difference in FF interval before and after the burst pacing in the three
      patients. CONCLUSION: The AERP was significantly shortened during AF, as compared
      with that during sinus rhythm, and the AERP shortening was more marked in
      patients with CAF than in patients with PAF. These clinical findings support the
      connection between the electrical remodelling and the occurrence and/ or
      perpetuation of the AF.

PMID- 12003107
TI  - Improving publicly-funded drug abuse treatment systems: the Target Cities
      Initiative.

PMID- 12003108
TI  - Gender differences in dually-diagnosed clients receiving chemical dependency
      treatment.
AB  - This article considers gender differences among 97 clients with dual diagnoses of
      severe mental illness and chemical dependency (46 male and 51 female).
      Comparisons are made at the time of their admission to an inpatient chemical
      dependency treatment program and at follow-up in cases where data are available.
      Many of the findings at time of admission are consistent with the few studies
      that have compared men and women with co-occurring mental and substance use
      disorders. For example, the women were more likely to have experienced emotional,
      physical, or sexual abuse, and they reported being charged with fewer types of
      crimes. Most differences at admission concerned psychiatric problems and
      family/social relations. Women reported that they were more bothered by their
      psychiatric symptoms and their family/social relations, but they also reported
      more happiness and closeness in some relationships. The women also said they had
      more relatives with alcohol, drug, and especially psychiatric, problems. At
      follow-up, gender differences in the family/social and psychiatric domains
      persisted. Findings suggest that men and women with dual diagnoses might benefit
      from different emphases in treatment programs.

PMID- 12003109
TI  - The San Francisco centralized intake unit: a description of participants and
      service episodes.
AB  - Using client data from the publicly-funded drug abuse treatment system in San
      Francisco, California, this study compared demographic characteristics of clients
      of a central intake unit (CIU) to those of clients who did not access the CIU,
      and examined characteristics of CIU episodes. The San Francisco CIU was intended
      to make appropriate referrals of CIU clients to treatment programs, and 47.9% of
      these episodes were followed by a subsequent treatment episode within 90-days of
      admission to the CIU. Of all individuals in the treatment system, a quarter had
      been to the CIU and as many as 9% of all treatment episodes were at the CIU. The
      majority of CIU episodes were short, consistent with the nature of assessment and
      referral services. These data suggest that incorporating strategies to enhance
      admissions to post-CIU services could increase CIU impacts. The post-CIU
      admission patterns were consistent with greater availability of outpatient and
      day treatment slots in the system. The pre-CIU admission patterns suggested that
      treatment agencies in the system used the CIU as a means to transition their
      clients into additional or longer-term treatment.

PMID- 12003110
TI  - Engaging substance abusers after centralized assessment: predictors of treatment
      entry and dropout.
AB  - High attrition continues to be an important issue for substance abuse treatment
      providers. This study examined factors contributing to treatment entry and
      dropout after referral from centralized assessment. Univariate analysis showed
      that individuals with a shorter wait after assessment were more likely to attend
      an initial treatment appointment, while those who reported a history of physical
      or sexual abuse or were on probation were significantly more likely to drop out
      of treatment early. Multivariate analysis revealed, first, that persons with a
      comorbid psychiatric diagnosis and those referred to outpatient rather than
      residential care were less likely to enter treatment; and, second, that persons
      on probation and with a history of physical or sexual abuse were more likely to
      be early treatment dropouts. Findings suggest that decisions to seek help and to
      accept help are distinct, and that program factors play a substantial role in
      treatment engagement and retention.

PMID- 12003111
TI  - Women are less likely to be admitted to substance abuse treatment within 30 days
      of assessment.
AB  - The information gathered in a centralized intake unit (CIU) allows payers and
      administrators to examine if there are access issues for their population. For
      this study, the authors examined whether there were gender differences in the
      rate at which people are admitted to treatment within 30 days of assessment. Of
      the 5,004 individuals seeking publicly-funded substance abuse treatment in
      Detroit for the years 1996-97, 50.3% of those assessed at the CIU actually
      entered treatment. Women (31% of the people assessed) had a lower rate of
      admission (45% for women versus 53% for men) a difference that was maintained
      even after controlling for known risk factors. Women who were given priority for
      admission (i.e., those who were pregnant, had children, or injected drugs) had a
      higher rate of admission than other women (73% versus 39%), but only 17% of the
      women presenting were included in the priority groups. Men who were injecting
      drugs (a priority group) also had a higher rate of admission than other men (83%
      versus 49%). In multivariate analysis controlling for priority groups and known
      risk factors, women were still less likely to be admitted to treatment within 30
      days of admission than men. Establishing priorities improves the rate of
      admission within 30 days of assessment for those groups, but more needs to be
      done to improve the admission rate for women. These results demonstrate that a
      CIU allows administrators to monitor for access issues.

PMID- 12003112
TI  - Interaction effects of treatment setting and client characteristics on retention
      and completion.
AB  - Client-treatment matching assumes treatment outcome will be improved if
      characteristics of clients are matched to specific elements of treatment. Few
      empirical studies, however, have examined matching across different types of
      treatment settings. The present research examined differences in demographics and
      substance-related problems in populations admitted to three substance abuse
      treatment settings--outpatient (n = 1132), intensive outpatient (n = 1190), and
      residential (n = 149)--and tested whether interactions between client
      characteristics and type of setting predicted rates of 30-day retention and
      treatment completion. In addition, three specific hypotheses based on prior
      theoretical and empirical investigations were tested. Client characteristics
      included demographic information (e.g., sex, age, race) and Addiction Severity
      Index (ASI) composite scores. Client-setting interactions were found for both
      retention and completion. All three hypotheses received at least partial support.
      Implications for client assignment and future research are discussed.

PMID- 12003113
TI  - Impact of centralized intake on case management services.
AB  - The Chicago Target Cities demonstration project was designed to improve the
      effectiveness and accessibility of substance abuse treatment in large
      metropolitan areas. The primary interventions included centralized intake (CIU),
      comprehensive standardized assessment procedures, and management of a centralized
      wait list. A part of this project, the effectiveness of a case management model
      implemented through the CIU, was tested. Participants were randomly assigned to
      one of two conditions, case management (CM) or no case management (No-CM). The
      primary objectives of the CIU case management model were to improve the show rate
      to treatment, provide referrals to ancillary services, and to support treatment
      completion. Participants in both groups could also receive other support services
      provided by staff for the treatment agencies. CM participants were significantly
      more likely to show to treatment (78.9%) than No-CM participants (71.8%). Case
      management was found to primarily improve the show rates for younger
      participants, who without CM were significantly less likely to show for treatment
      than older participants. CM participants were significantly more likely to
      receive referrals to non substance abuse treatment services than No-CM
      participants, although the number of referrals was low in both conditions. No
      differences were found in the amount or length of substance abuse treatment
      services received by participants in the two conditions.

PMID- 12003114
TI  - Treatment preparation in the context of system coordination serves inmates well.
AB  - A large percentage of jail inmates suffer from substance abuse problems; however,
      providing treatment in jail is difficult. Multnomah County's In Jail Intervention
      Program (IJIP) demonstrated an effective alternative. Finigan, Barron, and Carey
      (In press) and Barron and Finigan (1999) demonstrated that inmates with substance
      use problems, especially women, participating in IJIP experienced fewer rearrests
      and reincarcerations. To address the question of what led to these outcomes,
      quantitative data were abstracted from program, jail, and state administrative
      databases and were supplemented by face-to-face interviews with key informants,
      including program participants and former participants. In addition to their
      substance abuse problems, IJIP participants were chronic offenders who were more
      likely to be diagnosed with mental health problems. Results suggest that
      treatment preparation together with coordination of jail release and entry to
      treatment increased numbers enrolling in treatment and helped former inmates
      engage in treatment more quickly. Quantitative data suggest that the longer
      inmates stayed in IJIP, the more likely was completion of community treatment.

PMID- 12003115
TI  - Predictors of attrition in a longitudinal study of substance abusers.
AB  - Previous research has emphasized the importance of minimizing attrition in
      longitudinal studies. The authors examined the influence of demographic,
      clinical, and process factors on attrition from a longitudinal study of 286
      substance abusers recruited at a central intake unit. Univariate tests showed
      that those who completed three, six, and 12 month interviews had higher baseline
      alcohol and drug use and were more likely to provide three or more contacts when
      recruited, to be female, to have been married, and to have previously received
      substance abuse or psychiatric treatment. Multivariate logistic regression
      revealed that complete data participants (those who completed all three ASI
      interviews) were nearly three times more likely to have previously received
      psychiatric treatment and twice as likely to have completed an early engagement
      interview. In addition, they were twice as likely to be female, and nearly twice
      as likely to be employed, own a residence, have completed high school, and be
      married. Procedures that may help decrease study attrition are discussed.

PMID- 12003116
TI  - Impact of centralized intake on drug and alcohol treatment placement decisions.
AB  - The American Society of Addiction Medicine (ASAM) and others have asserted that
      matching persons to an appropriate level of care will result in more positive and
      cost-effective treatment outcomes. The Center for Substance Abuse Treatment,
      through its Target Cities demonstration project, proposed the implementation of
      centralized intake and the use of comprehensive standardized assessment
      procedures as mechanisms for improving the treatment process. As part of Chicago
      Target Cities, it was decided to implement ASAM criteria at the central intake
      units (CIU). A comprehensive assessment instrument was developed, assessors were
      trained, and decision protocols were designed to facilitate the implementation.
      This article examines the impact of these interventions on the placement decision
      process. The placement decisions of the assessors employed by individual
      treatment agencies before implementation of the CIU were compared to the
      placement decision process of the CIU assessors. The role of patient preferences,
      the information assessors used to make placement decisions, and the willingness
      of assessors to make the clinical judgments indicated by ASAM PPC-2 were
      examined. Results indicate that the CIU assessors' final treatment
      recommendations were more similar to what they thought was best for the patient,
      and less related to patient preference than those made by assessors at the
      individual treatment agencies. The CIU assessors also used a wider range of
      information when making their placement decisions than did the Pre-CIU assessors.
      Finally, the CIU assessors were more willing to rate patients on ASAM criteria
      than were the Pre-CIU assessors. Implementation of the ASAM PPC-2 at the CIUs
      produced the expected differences in the placement decision processes at the CIU
      from those observed at the treatment agencies. The results indicate that the
      implementation of ASAM PPC-2 is both feasible and produces expected changes in
      the placement decision process.

PMID- 12003117
TI  - Varieties of centralized intake: the Portland Target Cities Project experience.
AB  - To assess the possible influence of centralized intake on client outcomes,
      initial, six- and twelve-month Addiction Severity Index composite scores (in the
      alcohol, drug, legal and psychiatric areas) for clients who experienced provider
      intake were compared with scores for those going through two different models of
      centralized intake. Centralized intake clients were more likely than provider
      intake clients to have legal problems, and those legal problems became fewer over
      time. Clients from in-jail intake, including pretreatment services and
      accompanied placement, showed a greater initial and lower subsequent prevalence
      of drug, psychiatric and legal problems than the clients of the freestanding
      centralized intake. For all clients, psychiatric composite scores were powerful
      predictors of problems in alcohol, drug medical and legal areas, and psychiatric
      symptoms decreased over time. Since baseline differences in demographics and
      service assignment existed among the three groups, it was difficult to identify
      whether the outcome differences were due to the nature of the participants, the
      nature of the intake intervention, or both. However, the Portland Target Cities
      Projects's emphasis on in-jail centralized intake was associated with enhanced
      client outcomes.

PMID- 12003118
TI  - Effects of treatment history and centralized intake on drug treatment outcomes.
AB  - This study assesses differences between first-time treatment clients (n=90) and
      repeat treatment clients (n=361), including whether entering treatment through a
      central intake unit affects outcomes differently for the two groups. Interview
      data were collected at baseline, one-month and 12-month follow-up. Study groups
      were similar in gender, race and age, but repeat treatment participants were more
      educated, more likely to primarily use heroin and more likely to have ever
      injected drugs. First-time treatment clients were more likely to have been
      required to enter treatment, but less likely to have applied to another program
      or to be in the program they desired. First-time treatment clients were also more
      likely to be in outpatient or day treatment, and less likely to be in residential
      treatment. Problem severity decreased for both groups over time, with no
      significant differences between groups. There was one significant interaction
      effect of study group and length of stay on social problem severity, such that
      longer stays in treatment led to a greater reduction in social problems for
      repeat treatment clients. Route of treatment entry (CIU/non-CIU) was not
      associated with problem severity nor change in problem severity over time for
      either study group.

PMID- 12003119
TI  - Immigrant and native-born female heroin addicts in Israel.
AB  - There are an estimated 25,000 heroin addicts in Israel and nearly one out of
      every five is a woman. Also, about one fourth of the addict population immigrated
      to Israel from the former Soviet Union (mostly from Russia and the Ukraine) since
      1989. In this study, native born and immigrant female addicts were interviewed to
      develop an understanding of their background characteristics, patterns of drug
      use, and attitudes based on group status. Results show that the two groups of
      women are similar in many respects; however, differences do exist. Russian
      speaking women tend to be better educated and have a greater concern about their
      personal health and maintaining custody of their children. Additionally,
      immigrant women are more inclined to use heroin and other substances while
      receiving treatment and are more likely to have a father who abuses alcohol.
      Discussion is given to the study findings as well as issues relevant to the
      formation of policy regarding services to female addicts in the country.

PMID- 12003120
TI  - Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and
      fluorescein in nine solvents: improved absolute standards for quantum yields.
AB  - Absolute fluorescence quantum yields are reported for the rhodamine 6G cation and
      the fluorescein dianion dyes in nine solvents. This information is combined with
      previously reported fluorescence lifetimes to deduce radiative and nonradiative
      decay rates. Along the alcohol series from methanol to octanol, rhodamine 6G
      displays an increasing radiative rate, in parallel with the square of the
      refractive index increase, and a slightly decreasing nonradiative rate.
      Fluorescein is different: the apparent radiative rate actually decreases,
      suggesting that the emissive species is perturbed in some fashion. For both dyes,
      fluorescence yields are enhanced in D2O, rising to 0.98, in parallel with a
      corresponding increase in lifetimes. Protonated solvents invariably give shorter
      lifetimes and lower quantum yields, contrary to some previous speculation. From
      this work and an analysis of existing literature values, more precise values have
      been obtained for two previously proposed absolute quantum yield standards. The
      yield of fluorescein in 0.1 N NaOH(aq) is 0.925+/-0.015, and for rhodamine 6G in
      ethanol, it is 0.950+/-0.015. In both cases, the solutions are assumed to be in
      the limit of low concentration, excited close to their long-wave absorption band
      and at room temperature but may be either air-saturated or free of oxygen.

PMID- 12003121
TI  - In vitro investigation on the pH dependence of the absorption and fluorescence
      properties of the photosensitizer mTHPC.
AB  - Fluorescence excitation efficiency is of great importance for photodynamic
      diagnosis. Because usually a difference in the interstitial pH between normal and
      tumor tissue occurs, it is necessary to assess the impact of pH on the
      fluorescence emission intensity of the photosensitizer meta
      tetrahydroxyphenylchlorin (mTHPC) in this context. The results obtained by in
      vitro fluorescence measurements clearly indicate that pH values below 6 lead to a
      significant decrease in the fluorescence intensity. In the physiological range of
      pH 6.5-7.2, however, no pH dependence was found. Besides the decrease in the
      fluorescence intensity of mTHPC for pH < 6, changes in the spectral shape of the
      absorption were found. These changes can be utilized for "dual-wavelength ratio
      imaging," using mTHPC as a pH-sensitive indicator with the excitation pair 405
      nm/436 nm in the range of pH 3.5-6.

PMID- 12003122
TI  - Photochemical electron transfer reactions of tirapazamine.
AB  - The absorption and fluorescence spectra of 3-aminobenzo-1,2,4-triazine di-N-oxide
      (tirapazamine) have been recorded and exhibit a dependence on solvent that
      correlates with the Dimroth ET30 parameter. Time-dependent density functional
      theory calculations reveal that the transition of tirapazamine in the visible
      region is pi-->pi* in nature. The fluorescence lifetime is 98+/-2 ps in water.
      The fluorescence quantum yield is approximately 0.002 in water. The fluorescence
      of tirapazamine is efficiently quenched by electron donors via an electron
      transfer process. Linear Stern-Volmer fluorescence quenching plots are observed
      with sodium azide, potassium thiocyanate, guanosine monophosphate and tryptophan
      (Trp) methyl ester hydrochloride. Guanosine monophosphate, tyrosine (Tyr) methyl
      ester hydrochloride and Trp methyl ester hydrochloride appear to quench the
      fluorescence at a rate greater than diffusion control implying that these
      substrates complex with tirapazamine in its ground state. This complexation was
      detected by absorption spectroscopy.

PMID- 12003123
TI  - Photochemistry and phototoxicity of aloe emodin.
AB  - Photochemical pathways leading to the phototoxicity of the aloe vera constituent
      aloe emodin were studied. The results indicate a photochemical mechanism
      involving singlet oxygen to be the most likely pathway responsible for the
      observed phototoxicity. Aloe emodin was found to efficiently generate singlet
      oxygen when irradiated with UV light (phidelta = 0.56 in acetonitrile). The
      survival of human skin fibroblast cells in the presence of aloe emodin was found
      to decrease upon irradiation with UV light. A further decrease in cell survival
      was observed in D2O compared with H2O, suggesting the involvement of singlet
      oxygen as the primary pathway. Laser flash photolysis experiments were also
      carried out on aloe emodin alone and in the presence of various biological
      substrates. Aloe emodin proved to be relatively photostable (phi = 1 x 10(-4))
      and a poor photo-oxidant (E*red = +1.02 V). Only absorption bands caused by the
      triplet state of aloe emodin (lambdamax = 480 nm) and the aloe emodin conjugate
      base (lambdamax = 520 nm) were observed in the transient spectra.

PMID- 12003124
TI  - Singlet molecular oxygen quenching ability of carotenoids in a reverse-micelle
      membrane mimetic system.
AB  - The influence of the medium heterogeneity upon the bimolecular rate constants for
      the physical quenching, kq, and chemical quenching, kr, of singlet molecular
      oxygen O2(1deltag) by seven natural and three synthetic carotenoids (CAR) with
      different substituent patterns was studied in a reverse micelle system of sodium
      bis(2-ethylhexyl)sulfosuccinate, hexane and water. Because O2(1deltag) was
      generated inside the water pools of the reverse micelles by photosensitization of
      the water-soluble dye rose bengal and the CAR are mainly located in the external
      hexane pseudophase, the quenching process was interpreted using a pseudophase
      model for the partition of 02(1deltag) between the water pools and the organic
      pseudophases. The kq values were mainly dependent on the extent of the double
      bond conjugation of the CAR, as demonstrated by a good empirical relationship
      between log(k(q)) and the energy E(S) of the longest wavelength transition pi-
      >pi* of the CAR. In contrast, the kr values were almost independent of the extent
      of the double-bond-conjugated system and about four orders of magnitude lower
      than kq. However, in all cases, CAR photobleaching was observed with the
      formation of various oxidation products, depending on the photosensitization
      time. Chromatographic and spectroscopic product analysis for the reaction
      products of beta-carotene with O2(1deltag) indicated the formation of the beta
      carotene-5,8-endoperoxide as the primary oxidation product.

PMID- 12003125
TI  - The light-induced reactions of tryptophan with halocompounds.
AB  - The light-dependent reaction between N-acetyl-L-tryptophanamide (NATA) and
      chloroform has been examined using fluorescence, NMR and reverse phase
      chromatography. The emission of NATA in the presence of CHCl3 decreases at 360 nm
      and increases at longer wavelengths (approximately 480 nm) upon illumination with
      280 nm light. The action spectrum for the formation of the 480 nm emitting
      product(s) has the same shape as the excitation spectra of the indole fluorophore
      in NATA. The pH of the solution decreases as the reaction proceeds. The reaction
      rate depends on the intensity of the illumination and is of the first order with
      respect to both [NATA] and [CHCl3]. NMR and reverse phase chromatography results
      demonstrate that multiple products are formed. The reaction products give new
      peaks between 8.9 and 10.5 ppm in the 1H-NMR that are assigned to -CHO groups,
      which are added to the indole ring. Some of the products react with 2,4
      dinitrophenylhydrazine and thus confirm this assignment. A scheme is proposed in
      which the excited indole gives off a solvated electron to initiate a series of
      steps that yield indole derivatives in which a -CHO group has replaced a -H in
      the indole ring. Similar reactions are observed when 5-hydroxytryptophan, 5
      fluorotryptophan or N-methylindolacetate is used instead of tryptophan or when
      the chloroform is replaced with other trichlorinated compounds, such as
      trichloroacetic acid, trichloroethanol and trichloroethane, as well as the
      tribrominated compound, bromoform, and the monoiodinated compound, iodoactetate.

PMID- 12003126
TI  - Estimation of pedestrian level UV exposure under trees.
AB  - Trees influence the amount of solar UV radiation that reaches pedestrians. A
      three-dimensional model was developed to predict the ultraviolet-B (UV-B)
      irradiance fields in open-tree canopies where the spacing between trees is equal
      to or greater than the width of individual tree crowns. The model predicted the
      relative irradiance (fraction of above-canopy irradiance) under both sunlit and
      shaded conditions under clear skies with a mean bias error of less than 0.01 and
      a root mean square error of 0.07. Both model and measurements showed that the
      locations people typically perceive as shady, low-irradiance locations in the
      environment can actually have significant UV-B exposure (40-60% of that under
      direct sunlight). The relationship of tree cover in residential neighborhoods to
      erythemal UV-B exposure for children and adults was modeled for the 4 h around
      noon in June and July. Results showed that human exposures (on the horizontal) in
      cities located at 15 and 30 degrees latitudes are nearly identical. For latitudes
      between 15 and 60 degrees, ultraviolet protection factors (UPF) were less than 2
      for less than 50% tree cover. A UPF of 10 was possible at all latitudes for tree
      cover of 90%.

PMID- 12003127
TI  - Relationship between the structural and functional changes of the photosynthetic
      apparatus during chloroplast-chromoplast transition in flower bud of Lilium
      longiflorum.
AB  - The relationship between the structural and functional changes of the
      photosynthetic apparatus in the flower bud of Lilium longiflorum during
      chloroplast-chromoplast transition was examined. Compared with green petals,
      there was a five-fold increase of the carotenoid content in yellow petals,
      whereas the chlorophyll content decreased five-fold. Absorption and emission
      fluorescence spectra of chromoplasts indicated that newly synthesized carotenoids
      were not associated with photosystem II (PSII) photochemistry. The maximum
      quantum yield in the remaining PSII reaction centers remained constant during the
      chromoplast formation, whereas the photosynthetic electron transport beyond PSII
      became inhibited, as indicated by a marked decrease of the O2 evolution capacity,
      of the photochemical quenching of chlorophyll-alpha fluorescence and of the
      operational quantum yield of photosynthetic electron transport. Deconvoluted
      fluorescence emission spectra indicated a more rapid degradation of photosystem I
      (PSI) complexes than of PSII during chromoplast formation. Compared with green
      petals, the spillover between PSII and PSI decreased by approximately 40% in
      yellow petals. Our results indicate that during chloroplast-chromoplast
      transition in the flower bud of L. longiflorum, PSII integrity was preserved
      longer than the rest of the photosynthetic apparatus.

PMID- 12003128
TI  - Direct near-infrared luminescence detection of singlet oxygen generated by
      photodynamic therapy in cells in vitro and tissues in vivo.
AB  - Singlet oxygen (1O2) is believed to be the major cytotoxic agent involved in
      photodynamic therapy (PDT). Measurement of 1O2 near-infrared (NIR) luminescence
      at 1270 nm in biological environments is confounded by the strongly reduced 1O2
      lifetime and probably has never been achieved. We present evidence that this is
      now possible, using a new NIR-sensitive photomultiplier tube. Time-resolved 1O2
      luminescence measurements were made in various solutions of aluminum
      tetrasulphonated phthalocyanine (AlS4Pc) and Photofrin. Measurements were also
      performed on suspensions of leukemia cells incubated with AlS4Pc, and a true
      intracellular component of the 1O2 signal was clearly identified. Time-resolved
      analysis showed a strongly reduced 1O2 lifetime and an increased photosensitizer
      triplet-state lifetime in the intracellular component. In vivo measurements were
      performed on normal skin and liver of Wistar rats sensitized with 50 mg/kg
      AlS4Pc. In each case, a small but statistically significant spectral peak was
      observed at 1270 nm. The 1O2 lifetime based on photon count rate measurements at
      1270 nm was 0.03-0.18 micros, consistent with published upper limits. We believe
      that these are the first direct observations of PDT-generated intracellular and
      in vivo 102. The detector technology provides a new tool for PDT research and
      possibly clinical use.

PMID- 12003129
TI  - In vitro photodynamic activity of a series of methylene blue analogues.
AB  - We have synthesized a series of symmetrical phenothiazines in which the methyl
      groups of methylene blue have been substituted by longer alkyl chains. Intrinsic
      photosensitizing ability was not altered by increasing the chain length. However,
      in vitro phototoxicity after 2 h incubation of RIF-1 murine fibrosarcoma cells
      followed the order n-propyl > n-pentyl > n-butyl > n-hexyl > ethyl > methyl, with
      ethyl and n-propyl analogues being 14- and 130-fold more phototoxic than
      methylene blue, respectively. All analogues also had an improved ratio of
      phototoxicity: dark toxicity (4:1 to 27:1) compared with methylene blue (3:1).
      Phototoxicity did not correlate with cellular phenothiazine levels, suggesting
      that the site of subcellular localization may be more important. After 2 h
      incubation of RIF-1 cells with the phototoxicity LD50 concentration, methylene
      blue and all analogues were observed to be localized in the lysosomes by
      fluorescence microscopy. On exposure to light, methylene blue relocalized to the
      nucleus, the ethyl analogue did not relocalize, whereas the more phototoxic n
      propyl - n-hexyl analogues relocalized to the mitochondria. Relocalization to the
      mitochondria was associated with an octanol: buffer partition coefficient > or =
      1. Therefore, the longer-chain analogues of methylene blue show significantly
      improved phototoxicity in vitro and, in addition, are expected to avoid the
      problems of mutagenicity associated with the nuclear localization of methylene
      blue.

PMID- 12003130
TI  - Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy
      has the potential to improve PDT dosimetry with a verteporfin-like
      photosensitizer.
AB  - In current clinical practice, photodynamic therapy (PDT) is carried out with
      prescribed drug doses and light doses as well as fixed drug-light intervals and
      illumination fluence rates. This approach can result in undesirable treatment
      outcomes of either overtreatment or undertreatment because of biological
      variations between different lesions and patients. In this study, we explore the
      possibility of improving PDT dosimetry by monitoring drug photobleaching and
      photoproduct formation. The study involved 60 mice receiving the same drug dose
      of a novel verteporfin-like photosensitizer, QLT0074, at 0.3 mg/kg body weight,
      followed by different light doses of 5, 10, 20, 30, 40 or 50 J/cm2 at 686 nm and
      a fluence rate of 70 mW/cm2. Photobleaching and photoproduct formation were
      measured simultaneously, using fluorescence spectroscopy. A ratio technique for
      data processing was introduced to reliably detect the photoproduct formed by PDT
      on mouse skin in vivo. The study showed that the QLT0074 photoproduct is stable
      and can be reliably quantified. Three new parameters, photoproduct score (PPS),
      photobleaching score (PBS) and percentage photobleaching score (PBS%), were
      introduced and tested together with the conventional dosimetry parameter, light
      dose, for performance on predicting PDT-induced outcome, skin necrosis. The
      statistical analysis of experimental results was performed with an ordinal
      logistic regression model. We demonstrated that both PPS and PBS improved the
      prediction of skin necrosis dramatically compared to light dose. PPS was
      identified as the best single parameter for predicting the PDT outcome.

PMID- 12003131
TI  - Photodynamic effects of mTHPC on human colon adenocarcinoma cells:
      photocytotoxicity, subcellular localization and apoptosis.
AB  - The photodynamic properties of meta-tetra(hydroxyphenyl)chlorin (mTHPC), a
      promising second-generation photosensitizer, were investigated using a human
      colon adenocarcinoma cell line (Colo 201 cells). The study on photocytotoxicity
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction
      assay showed that mTHPC was an effective photosensitizer on Colo 201 cells. The
      photocytotoxicity of mTHPC showed both drug and light dose-dependent
      characteristics. To reach LD50, namely, the dose at which 50% of the cells were
      killed, only 0.45+/-0.15 microg/mL of mTHPC and 3 J/cm2 of light dose were
      required. The presence of 10% fetal calf serum in culture medium significantly
      decreased the incorporation of mTHPC into cells and resulted in the reduction of
      photodynamic efficacy. Using confocal laser scanning microscopy, mTHPC was first
      shown to localize in lysosomes rather than in mitochondria. Furthermore, nuclear
      stainings demonstrated that photodynamic therapy with mTHPC induced apoptosis in
      Colo 201 cells.

PMID- 12003132
TI  - Platelet adhesion to photodynamic therapy-treated extracellular matrix proteins.
AB  - Photodynamic therapy (PDT) produces reactive species that alter vascular wall
      biology and vessel wall proteins. In this study, we examined platelet adhesion to
      PDT-treated (photosensitizer = Photofrin; fluence 100 J/cm2; lambda = 630 nm)
      extracellular matrix (ECM), fibrinogen, von Willebrand factor (vWF) and collagen
      Types I and III, under flow conditions in a recirculating perfusion chamber.
      Platelet adhesion was quantified by image analysis. The effect of PDT on vWF was
      assessed by measuring the binding of domain-specific antibodies to treated vWF.
      PDT significantly decreased platelet adhesion to the ECM, fibrinogen and vWF.
      However, PDT of collagen resulted in significantly increased platelet adhesion,
      with large aggregate formation. PDT affected mostly the A1 (glycoprotein [GP]-Ib
      binding site), A2 and A3 (collagen-binding site) domains of vWF but not the D'-D3
      (factor VIII-binding site) and B-C1 (GP-IIb/IIIa-binding site) domains. In
      conclusion, PDT can alter the ECM, resulting in decreased platelet adhesion.
      However, vessels with high collagen content, such as veins and small arteries,
      may become increasingly prone to thrombosis. The results of this study may thus
      play a role in understanding the thrombogenic properties and mechanisms of
      vascular PDT.

PMID- 12003133
TI  - Quantification of topically delivered 5-aminolevulinic acid by lontophoresis
      across ex vivo human stratum corneum.
AB  - Iontophoretic transport of the prodrug 5-aminolevulinic acid (ALA), which is used
      for photodynamic therapy (PDT), across human stratum corneum (SC) was studied
      quantitatively in vitro. The experiments were carried out in a three-compartment
      iontophoresis cell consisting of two electrode chambers equipped with Ag-AgCl
      electrodes, each separated from a central acceptor chamber by a sheet of SC,
      supported by a dialysis membrane, to mimic the side-by-side configuration
      normally used in vivo. Acceptor fluid samples were collected every hour for a
      period of 30 h in a fraction collector and analyzed by high-performance liquid
      chromatography-fluorometry after derivatization of the ALA. The iontophoretic ALA
      flux was studied as a function of the applied current density and the ALA
      concentration in the donor solution (1, 2.5 or 10% ALA). Depending on the ALA
      concentration in the donor cell, iontophoresis enhances the flux from close to
      the detection limit of 0.23 nmol cm(-2) h(-1) at zero current density (passive
      diffusion) to several hundred or thousand nanomoles per square centimeter per
      hour at current densities ranging from 100 to 1000 microA cm(-2). For example,
      interpolating our data we find that with an ALA concentration of 2% in the donor
      chamber, a current density of 0.255 mA cm(-2) transports 0.065 micromol cm(-2)
      ALA across the SC in 10 min (conditions of Rhodes et al. (1997), J. Invest.
      Dermatol. 108, 87-91). For passive diffusion we find that a 5 h topical
      application of 20% ALA results in the transport of 0.05 micromol cm(-2). Thus,
      the amount of ALA that passively diffuses through the SC in several hours,
      leading to therapeutic levels of protoporphyrin IX (PpIX) in the epidermis, can
      be delivered by iontophoresis in 10 min or less. However, because the formation
      of sufficient PpIX also requires several hours and also because the SC overlying
      skin lesions such as basal cell carcinoma (BCC) is not intact, the clinical
      benefit of topical ALA delivery by iontophoresis for PDT of BCC is yet to be
      established.

PMID- 12003134
TI  - Quantitative model calculation of the time-dependent protoporphyrin IX
      concentration in normal human epidermis after delivery of ALA by passive topical
      application or lontophoresis.
AB  - We present a mathematical layer model to quantitatively calculate the diffusion
      of 5-aminolevulinic acid (ALA) in the skin in vivo, its uptake into the cells and
      its conversion to protoporphyrin IX (PpIX) and subsequently to heme. The model is
      a modification and extension of a recently presented three-compartment model. The
      diffusion of ALA in the skin (epidermis, dermis) is described by the time
      dependent diffusion equation, and the sink in this equation accounts for ALA
      uptake in the cells. As boundary conditions, we use the ALA flux across the human
      stratum corneum (SC) in vitro during passive or iontophoretic ALA delivery as
      measured in vitro. Besides the diffusion equation, the model includes three
      additional equations, similar in form to those of the three-compartment model but
      with a different interpretation. Our additional equations are supposed to
      describe, respectively, the conversion of ALA in the cytoplasm to some
      intermediate compound in the mitochondria and the conversion of the latter to
      PpIX and of PpIX to heme. The first conversion is a process of the Michaelis
      Menten type, the other two are first-order rate processes. When fitted to the
      published data of PpIX fluorescence from normal human skin following
      iontophoresis of ALA, the model yields the tissue concentration of PpIX as a
      function of time after ALA application. The computed concentrations are in good
      agreement with the published phototoxic concentrations of PpIX in the tissues
      obtained from extraction. The model parameters obtained from the fit are
      subsequently used to compute the PpIX concentration in normal human skin after 4
      h topical application of 10, 20 and 40% ALA. This again yields the PpIX
      concentrations in tissue, in good agreement with the published values. The
      saturation of the PpIX concentration as a function of applied ALA concentration
      is calculated and agrees with clinical observations on the effectiveness of
      photodynamic therapy. Photobleaching is simulated, with subsequent resynthesis of
      PpIX in qualitative agreement with experiment. Finally, the model predicts that
      only 2.5-3.5% of the ALA entering the skin after passing the SC is converted to
      PpIX. The layered model is a considerable simplification of real skin, but its
      successful qualitative and quantitative reproduction of experimental data may
      encourage further studies to test and refine the model to improve our
      understanding of the kinetics of ALA and the synthesis of PpIX in the skin.

PMID- 12003135
TI  - Spectral heterogeneity in single light-harvesting chlorosomes from green sulfur
      photosynthetic bacterium chlorobium tepidum.
AB  - The fluorescence emission properties of single chlorosomes from the green sulfur
      photosynthetic bacterium Chlorobium (Chl.) tepidum are studied for the first
      time, using a total internal reflection fluorescence microscope. The fluorescence
      peak positions of bacteriochlorophyll (BChl)-c self-aggregates in a single
      chlorosome of Chl. tepidum were widely distributed in the wavelength region
      between 750 and 768 nm, and the standard deviation (s.d. = 4.1 nm, n = 51) was
      larger than that of single chlorosomes of Chloroflexus (Cfl.) (s.d. = 1.9 nm, n =
      50). The spectral heterogeneity among single chlorosomes from Chl. tepidum was in
      sharp contrast to those from Cfl. aurantiacus. The difference of chlorosomal
      spectral properties between Chl. tepidum and Cfl. aurantiacus at the single-unit
      level would be ascribed to the homolog composition of BChl-c--chlorosomes of Chl.
      tepidum have BChl substituted with various alkyl groups at both the 8- and 12
      positions, whereas light-harvesting BChl-c molecules in Cfl. chlorosomes have the
      same substituents at the 8- (ethyl group) and 12- (methyl group) positions.

PMID- 12003136
TI  - Pharmacokinetic and pharmacodynamic predictors of antimicrobial efficacy:
      moxifloxacin and Streptococcus pneumoniae.
AB  - Infections caused by Streptococcus pneumoniae place a considerable personal and
      economic burden on both patients and healthcare systems. As the resistance of S.
      pneumoniae to older antimicrobial agents such as penicillin, cephalosporins, and
      macrolides has increased, new antimicrobials with good activity against S.
      pneumoniae have been developed. The newer fluoroquinolones, including
      levofloxacin, gatifloxacin and moxifloxacin provide a safe and easy tool in the
      treatment of S. pneumoniae infections. However, there have been recent reports of
      levofloxacin-resistant strains of S. pneumoniae. Pharmacokinetics and
      pharmacodynamics can be used to determine which fluoroquinolone delivers the best
      coverage against S. pneumoniae, and also the 24-h AUC/MIC ratio (the AUIC)
      required to impede the emergence of bacterial resistance. Monte Carlo analysis
      suggests that moxifloxacin, with 4-8-fold greater activity and higher AUIC
      against S. pneumoniae than levofloxacin or gatifloxacin, provides the best
      coverage in terms of probability of cure and probability of minimizing emergence
      of resistance.

PMID- 12003137
TI  - Improving care for patients with respiratory tract infections.
AB  - The common respiratory tract infections of acute bacterial sinusitis, acute
      exacerbation of chronic bronchitis, and community-acquired pneumonia are
      responsible for millions of physician office visits every year. Despite advances
      in diagnostic testing and the development of new antimicrobial agents, these
      infections continue to contribute significantly to patient morbidity and
      mortality worldwide. Physicians are faced with multiple challenges in the
      management of patients with these diseases. These challenges include the
      selection of appropriate empiric therapy, the increasing emergence of resistant
      pathogens, patient noncompliance with therapeutic regimens, and the pressure to
      use cost-effective agents. Patients expect their antibiotics to work rapidly so
      that they can feel better quickly and return swiftly to their normal activities.
      Moxifloxacin has been developed to address many of these problems. Its efficacy
      has been demonstrated in an extensive clinical trial program the results of which
      are summarized below. The excellent pharmacokinetics and pharmacodynamics of
      moxifloxacin are covered elsewhere in this supplement, as is moxifloxacin's
      impressive safety and tolerability profile. Accordingly, this paper focuses on
      the clinical trial data currently available.

PMID- 12003138
TI  - An updated safety profile of moxifloxacin.

PMID- 12003139
TI  - Therapeutic options in an era of decreasing antimicrobial susceptibility.
AB  - Antimicrobial resistance among human pathogens has evolved to the multidrug
      resistant phase. Consequently, preserving antimicrobial efficacy is now an
      important clinical consideration when selecting an agent for therapy. A new, in
      vitro measure of potency called the mutant prevention concentration (MPC) allows
      clinicians to select antibacterials on the basis of an agent's ability to
      restrict the selection of resistant mutants. With some pathogens, C-8-methoxy
      fluoroquinolones are expected to be quite effective at restricting the selection
      of resistance because the value of MPC is below the human serum drug
      concentration achieved with standard doses. Clinical trials are now needed to
      determine how well preclinical profiles of these drugs correlate with the
      prevention of resistance.

PMID- 12003140
TI  - Influence of composition variations on the initial alteration rate of vitrified
      domestic waste incineration fly-ash.
AB  - Vitrification as a waste stabilization technology has often been considered
      applicable only to high-level radioactive waste for which, with the use of
      suitable additives, it yields a vitreous material with excellent chemical
      durability. It has become apparent in recent years that some waste forms-notably
      domestic waste incineration fly-ash purification residues--contain most of the
      ingredients of a vitrified material, although their composition variations are
      difficult to control. It is thus important to ensure not only that the materials
      are suitable for vitrification, but also that the resulting product exhibits
      acceptable long-term behavior under all circumstances. An initial study showed
      that, allowing for the compensation changes inherent in the melting process
      builtby EDF**, the residue collected by a single fly-ash dust separation defines
      a composition range within which the suitability of the vitrified material can be
      verified. "Vitrified material" refers to a melted material that contains no
      unmelted inclusions after cooling, but that may contain a variable fraction of
      crystallized phases. Five composition parameters were identified for the long
      term behavior assessment: the concentrations of the three major elements
      (silicon, aluminum and calcium), the total alkali metal (sodium and potassium)
      concentration, and the sum of the concentrations of two toxic elements (zinc and
      lead). The other elements were assumed constant at molar ratios representative of
      industrial wastes. The experimentation plan methodology applied to the
      composition range identified fourteen materials suilable for developing and
      validating first-order models of the material components. The fly-ash composition
      had a very significant effect on the degree and kinetics and crystallization in
      the vitrified material within the experimental composition range; the cooling
      rate was the determining factor for some of the fourteen materials studied. Two
      crystailine phases predominated: spinels rich in chromium, zinc, aluminum,
      magnesium and iron formed quickly on cooling, and accounted for about 2 vol% of
      the final material. Gehelenite (Ca2Al2SiO7) crystallized massively in some
      vitrified materials, accounting for more than half the final product and giving
      it a rock-like appearance. The effect of composition alone must therefore be
      distinguished from the effect of crystallization on the leaching behavior.
      Soxhlet tests were conducted for 14 days according to a protocol based on that of
      the French AFNOR draft standard NF-M 60313 to determine the maximum alteration
      rate in pure water at 100 degrees C. The measured rate ranged from 4 to 40 gm(-2)
      day(-1), illustrating the crucial role of the silicon concentration: within the
      test composition range, a low silicon content (< 30 wt%) tended to result in a
      significantly higher initial rate. However, the initial rate alone is not
      sufficient to assess the chemical durability of the material. Further tests will
      be carried out at 25 degrees C under conditions approximating those of a proposed
      disposal site to highlight the role of the alteration layer and the effect of
      rising concentrations in solution on the decreasing alteration rate.

PMID- 12003141
TI  - Solidification/stabilisation of arsenic bearing fly ash from the metallurgical
      industry. Immobilisation mechanism of arsenic.
AB  - When a fly ash waste material from a copper refining process containing large
      amounts of As2O3 is solidified using cement and lime, the arsenic concentration
      in the leachate can be lowered to ca. 5 mg/l in a saturated solution of Ca(OH)2.
      It is shown that the decrease of the concentration in the leachate, mainly of
      As(III), is due to the formation of insoluble CaHAsO3 in the leachate in the
      presence of Ca(OH)2. This method is compared with a method whereby use is made of
      oxidation of the waste before solidification to oxidise As(III) to As(V) using
      H2O2. The arsenic concentration in the leachate of the extraction test of an
      oxidised S/S sample was lowered to ca. 0.5 mg/l, a factor of 10 below the one for
      a non-oxidised sample. It is shown that the decrease of the concentration in the
      leachate mainly of As(V) is due to the formation of insoluble Ca3(AsO4)2 in the
      presence of Ca(OH)2. Extensive use was made of the speciation program MINTEQA2,
      to clarify the immobilisation of arsenic.

PMID- 12003142
TI  - Microstructure of Portland cement pastes containing metal nitrate salts.
AB  - In recent years, Backscattered Scanning Electron microscopy techniques (BSE),
      coupled with an image analysis system have been recognised as a powerful tool for
      quantitative analysis. This paper investigates the effect of metal additions (Ba,
      Cu, Ni, Zn, Cr(III), Pb and Cd) to Portland cement to produce a solidified
      product which meets the durability criteria quantified by the ratio of hydrated
      products and porosity. In addition, other indicators of the progress of cement
      hydration such as the bulk density and evaporable water of the solidified
      products were also measured. Metal concentrations of 0.1 and 1% per weight of
      cement at a constant water/cement ratio of 0.4 were examined. The same
      measurements were conducted on control samples of different water/ cement ratio.
      The results have shown that the control samples at different W/C ratio showed
      consistent trend in residual cement porosity, density and evaporable water
      content. It also showed that low dosage of metal nitrate additions can reduce
      cement hydration by up to 50% and at the same time reduce the observable
      porosity. Overall, this work has shown that Scanning Electron Microscopy (SEM)
      and image analysis are powerful tools and could be used to quantify the
      observable porosity and cement hydration in solidified systems.

PMID- 12003143
TI  - A dynamic leaching method for the assessment of trace metals released from
      hydraulic binders.
AB  - With respect to sustainable development, the leachability of trace metal from
      solid materials in contact with water has focused much attention over the years.
      Portland cements produced in industrial kilns generally contain from 10 to 300
      mg/kg of trace metals. The behaviour of these endogenous metals has been, in this
      regard, the target of different leaching studies. Many of these researches
      concluded that heavy metals release are lower than analytical detection limits.
      Although satisfying from an environmental point of view, it induces a lack in the
      knowledge about the trace metals behavior during the leaching of cement based
      material. Accordingly, we designed the CTG-LEACHCRETE device, a dynamic leaching
      system (modified Soxhlet type) that overcomes this difficulty and allows long
      term monitoring. The experimental procedure is presented and preliminary results
      are discussed.

PMID- 12003144
TI  - Chemical changes and leachate mass balance of municipal solid waste bottom ash
      submitted to weathering.
AB  - A study on the chemical stability of municipal solid waste (MSW) bottom ash
      submitted to weathering was carried out in order to identify and quantify the
      physico-chemical maturation mechanisms in a large heap (375 tonnes) over a period
      of about 18 months. The mineralogy and chemical composition of MSW bottom ash
      were analysed on fresh and maturated material. Calcite is the predominant newly
      formed mineral during bottom ash maturation, combined with aluminium hydroxides
      and various sulphates. Lead and zinc are trapped primarily by newly formed
      carbonates. Monitoring of the pore water and the outlet leachates revealed a
      marked contrast in the physico-chemical conditions within the heap and at the
      outlet. The salinity of the fluids peaked at around 16 g/l within the first few
      weeks and then progressively decreased to fluctuate between 5 and 8 g/l. Due to
      the high pH of the pore water, the average concentrations of heavy metals in the
      heap are high: 42.7, 9.6 and 0.8 mg/l for Cu, Pb and Zn. At the heap outlet,
      however, the leachates are buffered by carbonate precipitation due to
      equilibration with atmospheric CO2. Copper complexed as a chloride at the outlet
      remains at a relatively high concentration (10.2 mg/l), whereas Pb and Zn
      concentrations are below the limit of detection (<25 microg/l). A mass balance
      carried out over the 18 months of monitoring indicated that 86% of remobilized
      material within the heap is evacuated from the system. Within the heap,
      carbonation trapped 43 and 54% of the calcium and bicarbonate flux. The copper,
      lead and zinc flux at the heap outlet represent only 34, 18 and 19% of the actual
      remobilized mass of heavy metals.

PMID- 12003145
TI  - Weathering of a MSW bottom ash heap: a modelling approach.
AB  - Establishing plausible predictive scenarios represents a challenge for the long
      term evolution of waste such as municipal solid waste bottom ash. These systems
      are characterized by complex and sometimes poorly understood physico-chemical
      mechanisms. The long term prediction of the evolution of such systems must be
      based on a dynamic approach involving their study in space and time. A
      preliminary outline of a model integrating chemistry and mass transfer is
      currently being tested by BRGM on the results obtained from a 16-month monitoring
      survey of a pilot bottom ash heap subjected to meteoric weathering. The model is
      based on a simplified coupled chemistry-transport approach using mass action laws
      and Kinetics chemical model (the Networks of Chemical Reactors approach). This
      modelling approach is used to monitor the evolution in chemical composition of a
      column of meteoric water percolating through the pilot bottom ash heap. The
      system is divided into representative elementary volumes (chemical reactors) on
      the basis of the major chemical and mineralogical zonations identified in the
      system.

PMID- 12003146
TI  - Characterization of the leaching behaviour of concrete mortars and of cement
      stabilized wastes with different waste loading for long term environmental
      assessment.
AB  - The leaching behaviour of cement-based products-both construction products and
      cement-stabilized wastes--have been shown to be similar after assessing the
      leaching characteristics by means of a pH dependence leaching test. This
      procedure is particularly suited to identifying the chemical speciation of
      materials. Geochemical modelling has shown a number of solubility controlling
      phases in this largely inorganic matrix, that can very well explain the observed
      leaching patterns as a function of pH. Understanding these relationships allows
      the prediction of leaching behaviour under other exposure conditions and to
      improve the ultimate quality of products, if so desired. The role of ettringite
      type phases for the binding of oxyanions in the pH range above pH 12 has been
      identified before and confirmed in this work. The order of incorporation follows
      from the ratio between the maximum leachability at mildly alkaline pH and at high
      pH. Increased levels of sulfate negatively influence the binding of oxyanions in
      cement-stabilized waste through site competition.

PMID- 12003147
TI  - Microbial influenced degradation of solidified waste binder.
AB  - Ordinary cement pastes with water/cement (w/c) ratios of 0.2, 0.4 and 0.5 were
      used to examine the chemical and physical effects of microbial influenced
      degradation (MID). Samples were exposed to an active culture of Thiobacillus
      thiooxidans or to sterile media containing sulphuric acid using an intermittent
      immersion technique. Acid consumption and Ca, Al and Fe releases are presented
      for an exposure period of 90 days. Exposed samples were also sectioned and
      analysed by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX).
      All cement paste samples were subject to significant degradation in either
      sterile acid media or the T. thiooxidans lixiviant. Corrosion depths observed
      from SEM examination of exposed samples were affected by the w/c ratio of the
      cement. The extent and rate of degradation were not apparent from the calculated
      rate of hydrogen ion consumption, or the leaching rates of Ca, Al and Fe. It was
      not possible to distinguish differences in corrosion due to the chemical and
      microbial influenced degradation from the results obtained to date and further
      work is focusing on modified procedures to address this.

PMID- 12003148
TI  - Effect of microbial activity on the mobility of chromium in soils.
AB  - The effect of microbial activity on the chemical state of chromium, in a
      contaminated soil located in the Rhjne-Alpes region (France), has been
      investigated. This soil contained 4,700 mg kg(-1) Cr, with about 40% present in
      the soluble hexavalent form. Indigenous microbial activity was found to
      significantly reduce Cr(VI) to the less mobile form (III) when the soil was
      incubated at 30 degrees C in an aqueous medium containing glucose and nutrients.
      A Cr(VI)-reducing strain of Streptomyces thermocarboxydus was isolated from the
      contaminated soil. The strain was found to metabolize Cr(VI) in a similar manner
      as an exogenous inoculum of Pseudomonas fluorescens LB300, and to precipitate
      chromium as a Cr oxyhydroxide with a gammaCrOOH-like local structure. The Cr(VI)
      reducing activity of S. thermocarboxydus was induced, or significantly
      accelerated, by the aggregation of bacterial cells or their adhesion to suspended
      solid particles, and was stimulated in pure culture by glycerol and chromate.

PMID- 12003149
TI  - A dynamic study of the sorption and the transport processes of cadmium in
      calcareous sandy soils.
AB  - The interactions of Cd2+ with silica and calcite were observed through laboratory
      dynamic experiments. Cd2+ sorption processes were characterised as a function of
      reaction kinetics in aqueous solutions saturated or not with respect to calcite.
      Chromatographic column experiments show that Cd2+ sorption on silica can be
      considered as a reversible equilibrate reaction which depends on water
      composition and pH. For a porous medium composed by a mixture of silica and
      calcite, the Cd2+ migration behaviours are predominantly controlled by calcite.
      The amount and the reversibility of sorbed Cd on calcite are strongly affected by
      kinetic limitations. Stirred flow through reactor experiments provide an original
      method to separate and characterise the 'fast' and 'slow' Cd sorption on calcite
      processes. The 'fast' Cd reversible adsorption isotherms and the rate of Cd
      subsequent uptake by 'slow' reactions are determined. In addition, the inhibition
      of calcite dissolution is observed as a function of sorbed Cd in order to provide
      a complete mechanistic database for coupled transport-geochemistry models.

PMID- 12003150
TI  - The Bacillus subtilis rec-assay: a powerful tool for the detection of genotoxic
      substances in the water environment. Prospect for assessing potential impact of
      pollutants from stabilized wastes.
AB  - The Bacillus subtilis rec-assay has been specially developed to detect
      genotoxicity in environmental water samples. The rationale of the B. subtilis rec
      assay is based on the relative difference of survival of a DNA repair
      recombination proficient strain and its deficient strain, which is interpreted as
      genotoxicity. This assay method can be very powerful in that it has higher
      sensitivity for the detection of mutagens in highly polluted waters than other
      bacterial mutation assays. Hydrophobic fractions from various environmental
      waters were fractionated by using XAD-2 resins and assayed, targeting the
      detection of organic genotoxic substances. Genotoxic response was detected in
      most of them, which revealed that many unknown micropollutants with genotoxicity
      occur in public water bodies. Positive response was also detected from a treated
      municipal solid waste (MSW) landfill leachate. Genotoxicity remaining in the
      treated effluent suggests that genotoxic micropollutants may pass through
      conventional water treatment processes such as activated sludge treatment
      process. Without proper control of waste quality and landfill facilities, waste
      landfill could be a heavy pollution source.

PMID- 12003151
TI  - Waste ecocompatibility in storage and reuse scenarios: global methodology and
      detailed presentation of the impact study on the recipient environments.
AB  - In 1995, the ADEME launched a research program called "Waste Ecocompatibility" in
      order to define a reliable methodology for measuring the impact of waste in
      storage or reuse scenarios. The French concept of "Ecocompatibility" is defined
      as the situation where the pollutant flux from waste disposed of or used in
      specified conditions is compatible with the environmental acceptance of the
      receiving environments. The chief feature of this definition is to integrate the
      evaluation of the three following terms: pollutants emission from the waste,
      transport of the pollutants from the waste to the receptor cells and the
      environmental acceptance of the receiving environments. The "Waste
      Ecocompatibility" program consisted of a literature survey and an experimental
      part. The literature study aimed to determine factors and waste characteristics
      to be considered for a reliable ecocompatility assessment, to provide an overview
      of the available tools for measuring those factors and characteristics and to
      propose a first approach of the methodology. In the framework of the experimental
      program, this approach was then applied to three theoretical scenarios to
      validate the laboratory tools (comparative study of laboratory and field results)
      and to calibrate the global methodology. This paper deals with the results of the
      experimental program concerning the impact study on receiving environments:
      impact on plants and microorganisms living in soil, impacts on soil fauna and
      aquatic fauna. In other papers we intend to present the operational methodology
      for the assessment of waste ecocompatibility. It includes bio-assays at
      laboratory scale (microcosms), pilot scale (mesocosms) and in situ experiments
      (experimental prairie). To limit the use of in situ experiments other research
      works are necessary to validate bio-assays at laboratory or pilot scale.

PMID- 12003152
TI  - Methodological approach towards the definition of new storage conditions for
      inert wastes.
AB  - In 1997, the French Ministry of Environment launched studies aiming to define a
      specific regulation concerning inert waste disposal in order to limit potential
      impact of such facilities on the environment by fixing minimum requirements. A
      model (chemical model/hydrodynamic model) was developed to determine dumping
      conditions. This model was then applied on two defined scenarios (landfill
      surface, effective rainfalls...) in order to study the sulphate concentrations in
      aquifer system immediately downstream from the storage facility. Results allow us
      to determine in which conditions the sulphates concentrations are compatibles
      with the potentially drinkable character of the groundwater. They more
      specifically concern the nature of the waste disposed of, the efficient rainfalls
      and the landfill area.

PMID- 12003153
TI  - Calcium phosphate stabilization of fly ash with chloride extraction.
AB  - Municipal solid waste incinerator by products include fly ash and air pollution
      control residues. In order to transform these incinerator wastes into reusable
      mineral species, soluble alkali chlorides must be separated and toxic trace
      elements must be stabilized in insoluble form. We show that alkali chlorides can
      be extracted efficiently in an aqueous extraction step combining a calcium
      phosphate gel precipitation. In such a process, sodium and potassium chlorides
      are obtained free from calcium salts, and the trace metal ions are immobilized in
      the calcium phosphate matrix. Moderate calcination of the chemically treated fly
      ash leads to the formation of cristalline hydroxylapatite. Fly ash spiked with
      copper ions and treated by this process shows improved stability of metal ions.
      Leaching tests with water or EDTA reveal a significant drop in metal ion
      dissolution. Hydroxylapatite may trap toxic metals and also prevent their
      evaporation during thermal treatments. Incinerator fly ash together with air
      pollution control residues, treated by the combined chloride extraction and
      hydroxylapatite formation process may be considered safe to use as a mineral
      filler in value added products such as road base or cement blocks.

PMID- 12003154
TI  - Evaluation of toxic and genotoxic potential of stabilized industrial waste and
      contaminated soils.
AB  - Artificial aqueous samples (eluates, percolates, immersion waters) were obtained
      from contaminated soils and stabilized industrial wastes. The toxicity and
      genotoxicity of these aqueous fractions have been evaluated in vivo in the
      aquatic larvae of the amphibian Xenopus laevis. Four biotests have been applied:
      a test of subchronic toxicity and three biomakers: (1) measurement of the
      activity of ethoxyresorufine-o-dealkylase in the liver, (2) detection of DNA
      adducts in the liver and the blood, and (3) measurement of the rate of
      micronuclei in the erythrocytes. Biological datas were completed through a
      chemical analysis. The main conclusions of this study are: The importance of
      integrating different toxicity criterias into a biological battery (phenotypic
      and genotypic criterias). Some aqueous extracts did not seem to be very toxic,
      whereas their genotoxic effects were rather significant [e.g. the stabilized
      Municipal Solid Waste (MSW) ashes]. The importance of coupling together chemical
      and biological approaches to refine the impact. Actually, some eluates
      (lixiviation or percolation) coming from polluted soils appeared to be very
      poorly loaded with pollutants, whereas the toxic and genotoxic impact of these
      complex matrices were rather noticeable. In addition, when applying the leaching
      standardized procedure, the hazardous potential of the two analysed soils may be
      underestimated if the results on percolates and on eluates have been compared.
      This study highligths the importance of coupling the tools of characterization
      and preparation of samples to be analysed according to the objectives to be
      reached.

PMID- 12003155
TI  - Leaching of inorganic contaminants from cement-based waste materials as a result
      of carbonation during intermittent wetting.
AB  - Characterization of the leaching behavior of wastes is a crucial step in the
      environmental assessment for reuse or disposal scenarios. The release of
      inorganic contaminants from waste materials is typically evaluated by tank
      leaching of continuously water-saturated material. However, materials, in many
      field or management scenarios, experience cyclic wetting and drying under varied
      environmental conditions (i.e. variable relative humidity, atmospheric CO2 or CO2
      from biologic activities). During periods of storage in an unsaturated
      environment, many processes may occur that can influence the release potential
      and release rate of inorganic constituents. The research presented here was
      carried out to examine how the phenomena of carbonation during drying influence
      the release of inorganic contaminants from Portland cement-based materials during
      cyclic wetting and storage. Batch equilibrium leaching tests were used to
      determine constituent solubility as a function of pH. Dynamic leaching tests on
      monolithic material were carried out to determine the rate of constituent release
      as a function of leaching time and intermittent storage conditions. This paper
      presents the results observed for three typical waste constituents, arsenic,
      cadmium and lead.

PMID- 12003156
TI  - Waste stabilization and environment: towards the definition of waste
      stabilization objectives, taking into account the potential health and
      environmental impacts.

PMID- 12003157
TI  - The effect of sleep fragmentation on daytime function.
AB  - It is clear from this literature that fragmented sleep is less restorative than
      consolidated sleep, and leads to sleepiness-related daytime impairment. The
      optimal approach to the quantification of sleep fragmentation continues to be
      debated. Modest and erratic correlations between measures of sleepiness and
      traditional measures of EEG arousals have pushed investigators to try and find
      more sensitive measures of sleep fragmentation. Simply correlating various
      measures of sleep fragmentation with a measure of sleepiness has significant
      limitations. Since sleep fragmentation is not the only factor affecting daytime
      sleepiness, these correlations can be misleading. For example, a subject with
      severely fragmented sleep will show elevated sleepiness during the day. However,
      the overall correlation may be reduced because lack of fragmented sleep does not
      guarantee that the level of sleepiness will be low. Multivariate statistical
      modeling is needed to account for sources of variance simultaneously in the
      prediction of daytime sleepiness. In this way it may be possible to identify the
      optimal definition of sleep fragmentation. More studies are needed that evaluate
      "sub-cortical" arousals, EEG arousals, and daytime function simultaneously.
      Ideally, clarification of these measurement issues will lead to an improved
      understanding of sleep structure and the mechanism through which sleep
      fragmentation impacts daytime function.

PMID- 12003158
TI  - Age-related changes in control of blood pressure and heart rate during sleep in
      the rat.
AB  - STUDY OBJECTIVES: The aim of this study was to determine age-related changes in
      the control of mean arterial pressure (MAP) and heart rate (HR) during sleep, and
      its relationship to the baroreflex in aging. DESIGN: MAP, HR, body temperature
      (TP), spontaneous activity (ACT), and sleeping/waking duration were monitored for
      24 hours in groups of young (10-12 wk old) and old (23-24 mo old) rats. SETTING:
      The sleep laboratory at the University of Tokushima. PARTICIPANTS: Subjects were
      8 young (10-12 wk old) and 7 old (23-24 mo old) Wistar rats. INTERVENTIONS:
      Reflex control of HR was evaluated by examining various pressure responses to an
      intravenous bolus injection of phenylephrine and sodium nitroprusside.
      MEASUREMENTS AND RESULTS: MAP and TP were recorded by a radiotelemetry system. HR
      was detected from the AP signal. ACT was counted by a photo-sensor system. In the
      case of old rats, the sensitivity of baroreflex control of HR was significantly
      depressed, and the spontaneous increase of MAP and HR during REM sleep and the
      MAP drop at the end of REM sleep were significantly enhanced. The old rats showed
      no large deterioration of the circadian profiles of MAP, HR, TP, and the amount
      of sleep. CONCLUSIONS: The baroreflex dysfunction is considered to appear in an
      early stage of the aging process, and to affect the control of MAP and HR during
      sleep.

PMID- 12003159
TI  - The relationship between chronically disrupted sleep and healthcare use.
AB  - STUDY OBJECTIVES: To determine whether chronic sleep deprivation, sleep
      disruption, sleepiness, insomnia, and OSA are associated with increased
      healthcare use in a community-based population. DESIGN: Cross-sectional study.
      SETTING/PARTICIPANTS: 6440 Sleep Heart Health Study (SHHS) participants recruited
      from ongoing cohort studies. INTERVENTIONS: N/A. MEASUREMENTS: Polysomnography
      results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin
      saturation below 90% (CT90), arousal index) as well as data on sleep related
      symptoms, medication use, and chronic illness. The indirect measure of predicted
      healthcare utilization was the modified Chronic Disease Score (CDS) calculated
      from medication data. RESULTS: After adjustment for age, gender, BMI and study
      site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS
      that were 6%-9% higher than the lowest quartiles. The adjusted mean CDS for
      subjects with sleep apnea was similar to that for subjects with hypertension,
      chronic bronchitis or asthma and 18% greater than the mean CDS for subjects
      without sleep apnea. Among subjects who did not have significant sleep-disordered
      breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough
      sleep were associated with increased CDS. CONCLUSIONS: This study demonstrated an
      association between subjective complaints of daytime sleepiness, inadequate sleep
      time, insomnia as well as objective measures of severity of SDB, and an indirect
      measure of healthcare utilization in a community-based sample. Though the percent
      increases in healthcare utilization observed were modest, the prevalence of these
      factors in the general population is high, and may therefore be associated with a
      substantial cost burden to the healthcare system.

PMID- 12003160
TI  - Melatonin and zopiclone: the relationship between sleep propensity and body
      temperature.
AB  - STUDY OBJECTIVES: The sleep promoting effects of the sedative-hypnotics,
      melatonin and temazepam, have been associated with a decline in core body
      temperature (Tc). To determine whether changes in body temperature are a general
      feature of sedative-hypnotics, the present study compared the sleep inducing,
      core and peripheral temperature effects of melatonin, with those of zopiclone.
      DESIGN: Subjects were supine from 08:00-21:30 h and received melatonin, zopiclone
      or placebo at 14:00 h. SETTING: Individual, light and temperature controlled
      bedrooms. PARTICIPANTS: 12 healthy, young, adults (7m, 5f; 20.3 +/- 0.6 years).
      INTERVENTIONS: Melatonin (5mg), zopiclone (Imovane; 7.5 mg) and placebo were
      administered in a double-blind, crossover design. MEASUREMENTS AND RESULTS: From
      11:00-20:00 h, modified hourly multiple sleep onset latency tests (MSLT) of a 20
      min duration were conducted and heart rate (HR) was recorded. Tc and foot
      temperature (T(Ft)) were recorded continuously using thermistors. Compared with
      placebo, melatonin and zopiclone significantly reduced sleep onset latency (SOL)
      to stage 1 (by 3.50 +/- 0.73 min and 6.80 +/- 0.61 min, respectively) and reduced
      Tc (by 0.22 +/- 0.02C and 0.14 +/- 0.02C, respectively). For melatonin, Tc
      declined as the result of an increase in peripheral heat loss (increase in T(Ft)
      of 1.65 +/- 0.43 degrees C), and possibly a reduction in heat production as
      indicated by a decrease in HR (4.56 +/- 0.94 bpm). Zopiclone increased heat loss
      (increase in T(Ft) of 1.43 +/- 0.68C) and had no cardiac effects. For melatonin,
      a negative association was found between Tc (mean r=-0.43), however, this
      association was only weak for zopiclone (mean r=-0.23). CONCLUSIONS: These
      results suggest that body temperature changes may be a general feature of
      sedative-hypnotics. The potential role of this effect in the promotion of sleep
      appears to vary between agents.

PMID- 12003161
TI  - The association between daytime sleepiness and sleep-disordered breathing in NREM
      and REM sleep.
AB  - BACKGROUND: Daytime sleepiness is common in patients with sleep-disordered
      breathing. Although respiratory events during sleep are associated with the
      occurrence of daytime sleepiness, the differential impact of these events during
      non-rapid eye movement (NREM) and rapid eye movement (REM) sleep on daytime
      sleepiness has not been well characterized. STUDY OBJECTIVES: To determine the
      effect of respiratory events during REM sleep and NREM sleep on daytime
      sleepiness, as assessed by the multiple sleep latency test (MSLT). DESIGN: Cross
      sectional study. SETTING: University-based sleep disorders laboratory.
      PARTICIPANTS: Patients referred for polysomnography and daytime MSLT (n=1,821).
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The study sample was initially
      divided into quartiles based on the level of the apnea-hypopnea index (AHI)
      during NREM sleep. Within the first NREM-AHI quartile (NREM-AHI < 8.3 events/hr),
      the association between REM-related respiratory events and daytime sleepiness was
      examined using the method of Kaplan-Meier analysis and Cox proportional hazards
      regression. After adjusting for age, gender, body mass index, and the duration of
      NREM and REM sleep, REM-AHI was not associated with daytime sleepiness (Relative
      Risk: 1.01; 95%CI: 0.94-1.10). Similarly, no significant association was observed
      between REM-AHI and the MSLT in patients within the second through fourth NREM
      AHI quartiles. In contrast, increasing severity of disordered breathing during
      NREM sleep was associated with daytime sleepiness. For a 10-point increase in
      NREM-AHI, the adjusted relative risks for daytime sleepiness in the second
      through fourth NREM-AHI quartile were 1.21 (95%CI: 1.01-1.46), 1.20 (95%CI: 1.05
      1.37), and 1.10 (95%CI: 1.04-1.16), respectively. CONCLUSION: Sleep-disordered
      breathing during NREM sleep, but not REM sleep, is associated with increased risk
      of daytime sleepiness.

PMID- 12003162
TI  - Excessive daytime sleepiness and risk of occupational injuries in non-shift
      daytime workers.
AB  - STUDY OBJECTIVES: Only a few studies have examined the possible association
      between excessive daytime sleepiness (EDS) and risk of occupational injuries, and
      most of them were based on self-reports. This study tested this association in
      daytime workers using injury data taken from organizational archives. DESIGN: A
      retrospective and prospective study. It covered injury occurrence during two
      years prior to a sleep disorder assessment/education procedure and injury
      occurrence in the following year. The workers were given the assessment results
      and, when applicable, a letter to the treating physician. SETTING: Eight
      industrial plants. Lectures and discussions on sleep disorders, treatment, and
      implications to safety and quality of life were conducted with small groups who
      completed the sleep assessment questionnaire beforehand. The workers completed
      the sleep assessment questionnaire prior to the lecture/discussion. PARTICIPANTS:
      532 non-shift daytime workers. INTERVENTIONS: N/A. MEASURES AND RESULTS: A
      battery of questionnaires to assess EDS (by the Epworth Sleepiness Scale),
      suspected sleep disorders, sleep habits, and job and environmental conditions. Of
      the workers studied 22.6% had EDS. Most of those (96.3%) indicated that they had
      experienced this propensity for the past two years or more and 56% of them had
      experienced it for 10 years or more. Logistic regression analysis indicated that
      during the two-year period prior to the procedure, EDS was associated with an
      increased risk of sustaining a work injury (OR=2.23, 95% CI 1.30-3.81), even
      after controlling for possible confounders, including factory category, job and
      environmental conditions. In the year after the procedure, the injury rate
      decreased by one-third in the workers with EDS but remained unchanged in the
      workers without EDS. Consequently, the association between EDS and injury was no
      longer significant (OR=1.42, 95% CI 0.71-2.85). CONCLUSION: EDS is a prevalent
      phenomenon in non-shift daytime workers. Workers with EDS had over two-fold
      higher risk of sustaining an occupational injury. Providing workers with the
      assessment results and of the implications of EDS for safety may explain the
      decrease in occupational injuries upon follow-up. This decrease might have
      occurred either because of workers taking steps to reduce EDS and/or adopting
      safety behaviors.

PMID- 12003163
TI  - Neuroimaging of NREM sleep in primary insomnia: a Tc-99-HMPAO single photon
      emission computed tomography study.
AB  - STUDY OBJECTIVES: The objectives of this study were to: 1) demonstrate the
      feasibility of combining polysomnography and SPECT neuroimaging to study NREM
      sleep in primary insomnia and 2) evaluate possible functional CNS abnormalities
      associated with insomnia. DESIGN: Patients with insomnia and good sleeper
      controls were studied polysomnographically for three nights with a whole brain
      SPECT Scan of NREM sleep on Night 3. Groups were screened for medical/psychiatric
      history, substance use, and matched on age, body mass index, and education.
      SETTING: Sleep Research Laboratory and Nuclear Medicine Center PARTICIPANTS: Nine
      females, 5 patients with chronic psychophysiologic insomnia and 4 healthy good
      sleepers (mean age 36 years, SD 12, range 27-55). INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: Tomographs of regional cerebral blood flow during the
      1st NREM sleep cycle were successfully obtained. Contrary to our expectations,
      patients with insomnia showed a consistent pattern of hypoperfusion across all 8
      pre-selected regions of interest, with particular deactivation in the basal
      ganglia (p=.006). The frontal medial, occipital, and parietal cortices also
      showed significant decreases in blood flow compared to good sleepers (p<.05).
      Subjects with insomnia had decreased activity in the basal ganglia relative to
      the frontal lateral cortex, frontal medial cortex, thalamus, occipital and
      parietal cortices (p<.05). CONCLUSIONS: This study demonstrated the feasibility
      of combining neuroimaging and polysomnography to study cerebral activity in
      chronic insomnia. These preliminary results suggest that primary insomnia may be
      associated with abnormal central nervous system activity during NREM sleep that
      is particularly linked to basal ganglia dysfunction.

PMID- 12003164
TI  - Hypocretin-1 (orexin-A) levels in human lumbar CSF in different age groups:
      infants to elderly persons.
AB  - STUDY OBJECTIVES: Recent CSF and postmortem brain hypocretin measurements in
      human narcolepsy suggest that hypocretin deficiency is involved in the
      pathophysiology of the disease. In this study, we measured CSF hypocretin-1
      levels in various age ranges from infants to elder people to investigate the age
      dependent change of hypocretin concentrations. DESIGN: CSF hypocretin levels were
      compared by age groups and gender. ANOVA was used to examine the influences of
      these two parameters on CSF hypocretin levels. SETTING: University-based sleep
      and biology laboratory. PATIENTS OR PARTICIPANTS: Two hundred seventy two
      patients were included in this study, with 157 males and 115 females (0-79 years
      old). INTERVENTIONS: CSF samples were obtained by lumber punctures with informed
      consents. MEASUREMENTS AND RESULTS: Hypocretin-1 levels are not different in
      respect to gender or age, although our samples constitute a heterogeneous group
      with various disease conditions. CSF hypocretin-1 levels in infants under 4
      months are similar to those in adults. CONCLUSIONS: Early maturation of
      hypocretin transmission is suggested. No age- or gender-dependent changes in CSF
      hypocretin is observed.

PMID- 12003165
TI  - Long-term follow-up of periodic limb movements in sleep in older adults.
AB  - STUDY OBJECTIVES: The goal of this study was to examine the natural history of
      periodic limb movements in sleep (PLMS) in older adults. DESIGN: Prospective,
      longitudinal design. SETTING: San Diego area. PARTICIPANTS: Community-dwelling
      older adults. INTERVENTIONS: NA MEASUREMENTS AND RESULTS: Subjects participated
      in follow-up visits every few years. Sleep disorders were assessed at each visit
      using sleep questionnaires and overnight sleep recordings. Changes in PLMS over
      time were examined as well as variables that were associated with change. Average
      PLMS did not change over time, although there was considerable variability within
      the sample. In women, changes in PLMS were associated with changes in sleep
      disordered breathing. This relationship was not found in men. CONCLUSIONS:
      Although the prevalence of PLMS is high for older adults, the severity of the
      disorder does not progressively worsen with increasing age.

PMID- 12003166
TI  - Short note: oral contraceptives and sleep in depressed and healthy women.
AB  - STUDY OBJECTIVES: To evaluate the effects of oral contraceptives (OCs) on sleep
      EEG in healthy women and in those with major depressive disorders (MDD). DESIGN:
      This archival study selected participants who had sleep EEG measured over two
      consecutive nights, following a five-day regularized sleep-wake routine. Between
      groups multivariate analysis of variance (MANOVA) contrasted group and OC main
      effects and interactions on sleep architecture. SETTING: N/A PARTICIPANTS: Sixty
      eight women (ages 14-46 years) diagnosed with major depressive disorder (MDD), 13
      of whom were on OCs and 55 were not. Patients were symptomatic and untreated at
      the time of study. Thirty-seven healthy control women (ages 12-46 years), nine of
      whom were on OCs and 28 were not. INTERVENTIONS: N/A Measurements and Results: OC
      main effects were found for %SW and for REM latency. Significant OC x Group
      interactions were found for sleep latency and %REM. Sleep latency was
      significantly shorter on OCs, but only in healthy women. Women on OCs showed a
      shorter REM latency, more total REM time, and less slow-wave sleep than women who
      were not on OCs. CONCLUSIONS: The effects of OCs were generally larger in healthy
      women than in those with MDD. Moreover, OC use was associated with more disturbed
      sleep in healthy women. These findings imply that OC use may compromise sleep EEG
      differences between healthy and depressed women and may be more difficult to
      differentiate between depressed patients and healthy controls when sleep studies
      include women on OCs. These findings may also have implications for evaluating
      gender differences in sleep architecture.

PMID- 12003167
TI  - Bright light exposure at night and light attenuation in the morning improve
      adaptation of night shift workers.
AB  - With practical applicability in mind, we wanted to observe whether nocturnal
      alertness, performance, and daytime sleep could be improved by light exposure of
      tolerable intensity and duration in a real work place. We also evaluated whether
      attenuating morning light was important in adaptation of real night shift
      workers. Twelve night shift nurses participated in this study. The study
      consisted of three different treatment procedures: Room Light (RL), Bright Light
      (BL), and Bright Light with Sunglasses (BL/S). In RL, room light exposure was
      given during the night shift and followed by 1 hr exposure to sunlight or 10,000
      lux light the next morning (from 08:30 to 09:30). In BL, a 4-hour nocturnal light
      exposure of 4,000-6,000 lux (from 01:00 to 05:00) was applied and followed by the
      same morning light exposure as in RL. In BL/S, the same nocturnal light exposure
      as in BL was done with light attenuation in the morning. Each treatment procedure
      was continued for 4 days in a repeated measures, cross-over design. Nocturnal
      alertness was measured by a visual analog scale. Computerized performance tests
      were done. Daytime sleep was recorded with actigraphy. The most significant
      overall improvement of sleep was noted in BL/S. BL showed less improvement than
      BL/S but more than RL. Comparison of nocturnal alertness among the 3 treatments
      produced similar results: during BL/S, the subjects were most alert, followed by
      BL and then by RL. Real night shift workers can improve nocturnal alertness and
      daytime sleep by bright light exposure in their work place. These improvements
      can be maximized by attenuating morning light on the way home.

PMID- 12003168
TI  - Mitochondria and HIV infection: the first decade.
AB  - In the last few years, the interactions between mitochondria and infection with
      the human immunodeficiency virus (HIV) have received careful attention. Starting
      from the first studies regarding the presence of mitochondrial damage in cardiac
      tissue from patients who died of AIDS, researchers have investigated different
      aspects of the interactions between the virus and mitochondria, from acute
      primary infection to the final stages of the disease. Only recently a significant
      impulse to this type of research has come from the observation that the so called
      "highly active antiretroviral therapy" (HAART), a combination of potent
      antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue
      reverse-transcriptase inhibitors, is capable of damaging these organelles and
      cause a clinical syndrome called lipodystrophy. There is still an open debate
      concerning the exact responsibility of HAART as well as on metabolic pathways and
      mechanisms that are involved in the onset of lipodystrophy. The hypothesis that
      drug-induced damage to mitochondrial (mt) DNA is able to alter mitochondria
      functionality to a similar extent as that occurring in genetic disease affecting
      mtDNA suggests that mitochondria plays a crucial role in the pathogenesis of this
      syndrome. In this paper, data concerning the interactions between mitochondria
      and HIV infection will be reviewed.

PMID- 12003169
TI  - Functional analysis of HIV-specific cytotoxic T lymphocytes in antiviral-treated-
      and-naive patients: a preliminary report.
AB  - HIV-specific CTL functions were analyzed in HIV-infected individuals who did or
      did not receive antiretroviral therapy (ART). Results showed that gp 160 (env)
      stimulated perforin- and granzyme-expressing CTL, as well as perforin and
      granzyme-specific mRNA, were reduced in treated patients whereas TNFalpha was
      increased in ART-treated compared to naive individuals. Reduction of perforin and
      granzyme-expressing cells was not secondary to impaired IFNgamma production. A
      defect of CTL is observed in ART-treated individuals; this defect is not
      dependent on impaired Th cell function. These results reinforce the need for
      immunomodulants to successfully approach therapy of HIV infection.

PMID- 12003170
TI  - Natural killer cell function in HIV-1 infected patients.
AB  - A cross-talk between dendritic cells (DC) and resting natural killer (NK) cells
      leads to the activation of both cell populations, a process requiring cell-cell
      contact. When the number of activated NK cells overwhelms surrounding DC, they
      became able to kill specifically immature DC, a feedback mechanism to shut off DC
      mediated immune responses. DC, at the mucosal site, can capture HIV and transfer
      it to CD4+ T lymphocytes present in the regional lymph node thus giving rise to a
      productive infection; on the other hand, NK cells represent the first line of
      defence against viral infection. Our preliminary results suggest that during the
      early phases of an HIV infection, NK cell activity is not functionally
      compromised, but that infected cells might escape natural immune surveillance
      through several mechanisms, including a reduced lysis of autologous DC.

PMID- 12003171
TI  - Selective enrichment of CD30-expressing cells within the blast region of
      lymphocytes from patients with primary HIV infection (PHI).
AB  - Individuals experiencing a primary infection with HIV (PHI) are known to undergo
      a potent activation of their humoral and cellular immune response. We
      investigated the expression of CD30 in peripheral blood mononuclear cells (PBMC)
      from 15 PHI patients before their initiation of HAART, since elevated levels of
      its soluble form, sCD30, have been previously documented in the plasma/sera of
      PHI patients. We also analyzed other lymphocyte-associated activation markers,
      including CD69, CD25 and HLA-DR. When looking at total lymphocytes, HLA-DR was
      expressed on the majority of lymphocytes, followed evenly by CD69 and CD25, and
      last by CD30. Of note, we observed that 13 out of these 15 patients displayed a
      characteristic expansion of lymphocytes with larger morphology (termed blasts).
      When a morphologic gate was drawn on these blasts, the percentage of CD25-, CD69
      positive cells remained substantially unchanged, that of HLA-DR-positive cells
      augmented, but the the most striking increase occurred in the percentage of CD30
      expressing lymphocytes. Therefore, although all of the molecules studied are
      considered lymphocyte activation markers, CD30 is most likely to be expressed
      within cycling/proliferating cells of the lymphoblast fraction during the
      earliest phases of HIV infection.

PMID- 12003172
TI  - Primary HIV-1 resistance in recently and chronically infected individuals of the
      Italian Cohort Naive for Antiretrovirals.
AB  - The risk of acquiring HIV-1 drug resistance at time of infection has become a
      public health problem following the widespread use of antiretroviral drugs in
      developed countries. Although a number of studies have reported data regarding
      the prevalence of HIV-1 primary resistance in developed countries over the past
      years, limited knowledge is available regarding the proportion of mutations
      related to drug resistance in antiretroviral naive subjects with chronic HIV-1
      disease. In this study, we evaluated the prevalence of mutations in the reverse
      transcriptase (RT) and protease region both in a representative group of recently
      HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive
      patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients
      (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations
      for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by
      calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and
      protease inhibitors (PIs) respectively. Thymidine associated mutations were
      identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2),
      215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the
      changes associated with resistance to lamivudine (184V or 118I). No non
      nucleoside-RTI (NNRTI) mutations were present in the study period. Primary PIs
      mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note,
      mutations related to resistance to more than one class of antiretrovirals were
      present in one (1.5%). Among patients with chronic infection a large proportion
      (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more
      mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4
      patients carrying mutations to both classes. Among mutations associated with high
      level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases,
      T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one
      carrying both T215Y and M184V) (1.7%). Primary mutations associated with
      substantial resistance to PIs were found in only 5/347 patients (1.4%); all the
      other patients carried only secondary mutations. Prevalence of mutations
      associated with high-level resistance to antiretroviral drugs is stable in
      recently infected individuals and low in patients with established HIV infection.
      The potential impact of transmitted mutations on the response to first regimen in
      individuals carrying transmitted mutations needs to be assessed by prospective
      studies.

PMID- 12003173
TI  - Molecular and phylogenetic characterization of HIV variants in Italian primary
      HIV infections (PHI): identification of non-B subtype variants.
AB  - The distribution of Human Immunodeficiency Virus type 1 (HIV-1) clades is
      evaluated in primary HIV-1 infections (PHIs) occurring through sexual
      transmission in Lombardia, the Italian region with the highest
      prevalence/incidence of HIV-1 infections. The two primary inclusion parameters
      for enrollment were sexual transmission and < 1 year seroconversion. Thirty-four
      enrolled patients have been analysed so far at the molecular level, to
      characterize their infecting HIV-1 population. Two HIV-1 genomic regions with
      different rates of genetic variability, the hypervariable C2-V3 fragment of the
      env gene and the conserved 5' end of the gag p17, were amplified by Polymerase
      Chain Reaction (PCR) in peripheral blood mononuclear cells (PBMCs) and
      characterized by direct DNA sequence analysis. Pairwise nucleotide alignment and
      phylogenetic analyses show that, although with a high range of nucleotide
      variability, 32 out of the 34 HIV-1 isolates identified in this PHI cohort fall
      under the clade B genotype. The two remaining isolates, detected in a couple
      formed by a Nigerian woman and her Italian partner, consistently cluster with
      clade G standards in both sub-genomic regions. The amino acid sequences confirm
      this classification, showing clade-specific residues both in the V3 and p17
      regions. These data suggest that the B clade is still prevalently associated with
      acute primary HIV-1 infections occurring in Italy through sexual transmission.
      However, the significant intra-clade variability and the identification of non-B
      clades strongly indicate the relevance of continuous molecular monitoring of the
      HIV-1 isolates circulating in Italy, for prognostic evaluations as well as
      preventive and therapeutic strategies.

PMID- 12003174
TI  - HIV-1 DNA and RNA kinetics in primary HIV infection.
AB  - BACKGROUND: HIV-1 reservoir is early established during PHI. It is reduced, but
      not extinguished by early therapy: DNA containing cells are still detectable
      after months of successful viremia suppression. To define the best method to
      measure low level viral replication, we determined the extent of HIV reservoir in
      11 acutely infected patients and evaluated how it is renewed even during
      successful treatment. METHODS: Eleven acutely infected HIV patients were included
      in the study. Three where not treated with antiretroviral drugs while 8 underwent
      early aggressive antiretroviral treatment (HAART) which, in 3 cases, was
      associated to cyclosporin A (CsA) administration. HIV viremia was monitored by
      commercially available methods while HIV-DNA and cellular RNA quantitation were
      obtained by in house PCR and RT-PCR respectively, in the gag region. RESULTS:
      Significant CD4 recover and HIV viremia suppression were reached in a mean period
      of three to six months in all treated patients. The course of the HIV-DNA and of
      cellular HIV RNA reduction showed a similar trend. This variation was slower, if
      compared to plasma viremia and never reached undetectable levels, justifying the
      rebound of viremia observed at therapy interruption. CONCLUSIONS: These data
      suggest and confirm that complete abolition of viral replication is not achieved
      and viral reservoir may be re-expanded even after short term rebound of viremia.
      Scheduling of possible structured therapy interruption should be designed based
      on multiple virological parameters and on the individual characteristics of the
      patients.

PMID- 12003175
TI  - Primary HIV infection in infants: impact of highly active antiretroviral therapy
      on the natural course.
AB  - In the absence of any antiretroviral therapy, about one-third of infants with
      perinatally acquired HIV infection develop AIDS within the first months of life,
      while the remainder show slower disease progression. As the rate of viral
      replication during the first 3 months of life is strictly correlated with and
      predictive of disease outcome, any treatment that keeps the virus at low levels
      during primary infection might substantially modify the natural history of
      infection. Emerging data show that some infants treated early with highly active
      antiretroviral therapy have persistenty undetectable levels of HIV, and lack an
      HIV-specific immune response, despite preservation of immune functions. These
      findings strongly suggest that early therapeutic intervention might lead to a
      long-term suppression of viral replication.

PMID- 12003176
TI  - Granulocyte/monocyte apheresis induces sustained increases in CD4 T cells in HIV
      1 infected patients with poor CD4 T cell restoration after suppression of viral
      replication by HAART.
AB  - Current antiretroviral regimens (HAART) are generally effective in reducing viral
      replication to undetectable levels and inducing a raise in CD4 T cells. However,
      in approximately 5 to 15% of patients suppression of viral replication is not
      followed by an increase in CD4 T cells. Such patients may be at increased risk
      for opportunistic infections. Here we report the results from a phase II open
      label randomised trial on 30 patients classified as poor responders to HAART who
      were either subjected to eight consecutive cycles of selective monocyte apheresis
      or maintained under HAART alone. The results show that monocyte apheresis results
      in increased CD4 T cell counts which are maintained for at least 31 weeks after
      last apheresis. This effect was observed only on patients with complete
      suppression of viral replication. Other effects of monocyte apheresis included a
      strong reduction of TNF-alpha production in patients with high baseline levels of
      this cytokine and activation of resting T cells during the apheresis cycles. In
      two patients with high cellular HIV DNA load apheresis was followed by a 98%
      reduction, suggesting purging of infected cells. There was no evidence of
      increased viral replication during or after the apheresis cycles. The data show
      that monocyte apheresis is safe, well tolerated and may be indicated in patients
      who respond poorly to HAART.

PMID- 12003177
TI  - Role of hydroxyurea during structured treatment interruptions.
AB  - Highly active antiretroviral therapies (HAART) represent a major advance in the
      treatment of HIV infection. Although with HAART a substantial suppression of
      viral replication can be obtained, eradication of the virus from the body cannot
      be achieved. Therefore, HIV-infected subjects have to be treated for the rest of
      their lives. Long term treatment will increase the frequency of: i) drug-related
      side effects; ii) onset of drug-resistant viral strains; iii) non-adherence of
      the patients to the treatment. Structured treatment interruptions (STI)-HAART
      might represent a feasible alternative and preliminary studies have shown that
      STI-HAART might induce immune control in patients treated in the early stage of
      infection. This regimen does not produce similar effects in patients treated
      during the chronic phase of the infection. However, there are some clinical data
      suggesting a possible role of hydroxyurea (HU) in inducing control of HIV
      replication in patients with established infection. In this manuscript in vitro
      and in vivo data indicating that HU might play a major role in the setting of STI
      HAART will be presented.

PMID- 12003178
TI  - Successful simplification of HAART in patients with acute primary HIV infection.
AB  - Aggressive treatment has been advocated for the management of primary HIV
      infection (PHI), but the composition and the optimal duration of therapy are
      still to be determined. In addition, time to undetectable viral load (VL), rate
      and duration of VL suppression as well as subsequent therapeutic choices remain
      issues widely debated. We evaluated the rate and duration of VL suppression in 12
      consecutive patients with PHI given triple-drug treatment with zidovudine,
      lamivudine and indinavir (highly active antiretroviral therapy, HAART) at onset
      of the acute illness and subsequently switched to a simplified 2-NRTI-based
      regimen once VL suppression was maintained for at least 6 months. Throughout the
      study, no patient discontinued treatment because of symptoms attributed to the
      study medications. In the study population, undetectable VL was achieved after a
      median of 84 days (range: 67-135) on HAART and was maintained for a median of 194
      days (range: 179-205) before simplification. After switching to simplified
      maintenace, undetectable VL was maintained in all patients for at least 6 months.
      Only one patient experienced virological failure, plasma HIV-RNA remaining
      suppressed for a median foliow-up of 33 months (15-54) and T-CD4+ being steadily
      higher than 500/mL in the remaining patients. Our results suggest that
      simplification of HAART in patients promptly treated during PHI and maintaining
      undetectable VL for at least 6 months before simplification may be a valid option
      capable of controlling viral replication and maintaining an optimal immunological
      profile for a prolonged time.

PMID- 12003179
TI  - Implementation of an Italian multicentric care network for early HIV infection
      diagnosis: 1999-2001 report.
AB  - BACKGROUND: Diagnosis of a new HIV infection during the primary phase (PHI) is
      sometimes misleading in a primary care setting. Since 1999 the Italian network
      for the study of acute HIV infection (ISAI) has been operative. At the time of
      PHI diagnosis the case is reported to the coordinating centre and enrolled in the
      National Register which records all epidemiological, demographic and clinical
      information. PATIENTS AND METHODS: From 1999 to September 2001, 51 symptomatic or
      asymptomatic patients with diagnosis of primary HIV infection were signalled to
      the coordinating centre. At screening, assessments were: interview to collect
      demographic and epidemiological data, clinical history (regarding PHI signs and
      symptoms) and, if available, relevant index case information; physical
      examination; routine hematology and chemistry; lymphocyte count; plasma HIV-RNA.
      In a subset of patients PBMC HIV-DNA, HIV-RNA, resistance genotyping and HIV
      subtype characterization were assessed. RESULTS: 74.5% of patients were males and
      all but four were Italian. Hetero and homosexual contacts were the prevalent
      route of HIV transmission. Forty-five patients (89%) were symptomatic and the
      most frequent signs and symptoms were: fever, lymphadenopathy, malaise and
      pharyngodinia. Baseline reverse-transcriptase (RT) and protease (PR) genotyping
      analysis was available for 29 patients. Only one of 29 patients harbored a virus
      with a resistance-associated mutation in the RT region (215Y); NNRTI mutations
      were identified in 3 of 29 patients. In the remaining 20 (69%) patients no
      mutations were found in the RT region. Sequence data from PR region were
      successfully obtained in 21 patients. Only one of these had a high-level
      resistance mutation (46L); in an additional 10 cases 1 or more secondary
      mutations were identified. The remaining 10 patients harbored a PR region wild
      type virus. One patient presenting two secondary mutations in the PR region, even
      if highly adherent and tolerant to drug regimen, showed a slow viral load
      decrease. CONCLUSIONS: Our cohort confirms the uptrend of new infections through
      unsafe sexual contacts involving both homosexual and heterosexual couples.
      Genotype sequencing for antiretroviral resistant viral variants describes a low
      prevalence of RT resistance-associated mutations, as well as primary mutations in
      the PR region. On the contrary, a higher prevalence of PR gene polymorphisms and
      mutations is not known with any certainty to confer resistance to NRTI and NNRTI.
      The identification of antiretroviral drug resistant HIV strains is strategic for
      clinical and therapeutical intervention, even though from a public health point
      of view cost-efficacy must be considered.

PMID- 12003180
TI  - An observational study on patients treated or not for acute HIV infection.
AB  - BACKGROUND: A vast majority of HIV-infected subjects who experience HIV acute
      seroconversion actually receive treatment. Open questions are how can we identify
      patients who will be slow progressors or long-term non progressors, and, as a
      consequence, do not require treatment. METHODS: An observational retrospective
      study on patients who experienced acute HIV seroconversion from August 1995 to
      June 2001, who are still alive and followed as outpatients at the Clinic of
      Infectious Diseases of Modena, Italy. RESULTS: Twelve patients were studied. Five
      patients (45.4%) were treated during acute seroconversion, while 7 were not
      treated. Two of these seven subjects received antiretroviral treatment 12 and 26
      weeks after acute seroconversion. All the untreated patients were in good viro
      immunological condition 6 months after seroconversion, and 2 of them also after 3
      and 7 years. Patients who were treated showed a significant daily increase in
      CD4/CD8 T cell ratio with longer time spent on therapy (0.04% increase per day
      longer on antiretroviral therapy, p=0.02). CONCLUSIONS: This study suggests that
      treatment during primary HIV infection should not be considered in all patients.
      Randomized clinical trials enrolling patients with an asymptomatic primary HIV
      infection, with a high CD4 count and low HIV plasma viremia are needed to
      evaluate the indications for treatment in this subgroup of patients. On the other
      hand, this study confirms the good viro-immunological response obtained after
      treating patients during primary HIV infection.

PMID- 12003181
TI  - Potential role of immune modulation in the effective long-term control of HIV-1
      infection.
AB  - Recent advances in HIV-1 pathogenesis, and in defining virological and
      immunological responses to highly active antiretroviral therapy (HAART), along
      with the identification of the numerous drawbacks of HAART, have clearly
      demonstrated that the eradication of the virus is not a feasible therapeutic
      goal, and that there is an urgent need to develop other approaches to fight HIV-1
      infection. Novel therapeutic approaches of immune modulation have recently been
      evaluated in pilot clinical trials. First, treating primary HIV-1 infection with
      cyclosporin A (CsA) coupled with HAART to target massive immune activation
      extends the benefits achieved with HAART during primary HIV-1 infection and might
      contribute to the establishment of a more favourable immunological set-point
      affecting the ultimate pattern and rate of disease progression. Second, treating
      chronic HIV-1 infection in patients with long-term suppression of virus
      replication induced by HAART, with the addition of mycophenolate mofetil (MMF)
      reduces the pool of activated CD4+ T lymphocytes able to support productive HIV-1
      infection, and might have an indirect impact on the pool of resting, latently
      infected CD4+ T cells, contributing to its depletion in vivo. The important
      question is clearly whether these results will have an impact on the clinical
      management of patients with HIV-1 infection, determining the precise therapeutic
      function of drugs like CsA and MMF, thus investigating the effects of these drugs
      on residual viral replication and the decay of the latent reservoir, on long-term
      immunological benefit, and, ultimately, on clinical benefit.

PMID- 12003182
TI  - The effect of HAART on humoral immune response in primary HIV-1 infected
      patients.
AB  - The effect of Highly Active Antiretroviral Therapy (HAART) on binding and
      neutralizing antibody responses to human immunodeficiency virus type-1 (HIV-1)
      during primary and chronic infection was investigated. Seven patients HAART
      treated during primary infection, six HAART treated during chronic infection and
      five patients treated only with ZVD (Zidovudine) were analysed. HAART inhibited
      the development of anti env antibodies during primary infection. Administering
      HAART during primary infection usually did not substantially affect the
      development of weak neutralizing antibody responses against autologous virus.
      However, we demonstrated that very early treatment, during seroconversion, induce
      in some cases, a strong neutralizing antibodies against autologous virus. These
      results may be relevant for understanding how HAART may elicit a strong
      protective responses and may be useful in developing new strategies designed to
      achieve a long term control of the HIV infection.

PMID- 12003183
TI  - Anticancer activity and protein phosphatase 1 and 2A inhibition of a new
      generation of cantharidin analogues.
AB  - Cantharidin (Spanish Fly) is a natural toxin and an inhibitor of protein
      phosphatases 1 (PP1) and 2A (PP2A), which have key roles in cell cycle
      progression. We have synthesised two series of demethylated cantharidin
      analogues, one displaying an open-ring lactone configuration in solution (Novo-1
      to Novo-5) similar to cantharidin, the other showing a closed-ring lactone
      configuration (Novo-6 to Novo-10). In the present study, these ten agents were
      screened for in vitro PP1 and PP2A inhibition and cellular cytotoxicity in nine
      cancer cell lines of haematopoietic (L1210, HL60), ovarian (A2780, ADDP), osteo
      (143B), and colon (HCT116, HT29, WiDr, SW480) origin and one normal colon cell
      line (CCD-018). The open-ring series (IC50, PPI=2.0-4.8 microM, PP2A=0.2-0.5
      microM) maintained the PP2A selectivity of cantharidin (IC50, PPI=1.8 microM,
      PP2A=0.2 microM), although some were less potent. The closed-ring series (IC50,
      PPI=12.5->1000 microM, PP2A=5->1000 microM) were considerably less potent
      inhibitors, confirming the need of ring opening for inhibition. The cytotoxicity
      (IC50, 72 h, MTT assay) of cantharidin ranged from 6-15 microM, while the new
      analogues ranged from 14 to >1000 microM. Cytotoxicity of the agents did not
      consistently parallel the in vitro potency of protein phosphatase inhibition. A
      number of analogues showed colon cancer selectivity, particularly Novo-6, where
      the cytotoxicity ranged from 14-88 microM in the colon cancer cells and 275-680
      microM in all other cell lines including normal colon cells. The reason for this
      selectivity was not apparent and may involve additional intracellular targets.
      Cell cycle analysis showed cantharidin to enhance cell cycle progression as
      evident from an increased S-phase population and enhanced DNA synthesis,
      culminating in G2/M arrest and apoptosis. With Novo-1 and Novo-6, the cell cycle
      changes paralleled the cytotoxicity responses, with the predominant effect of
      G2/M cell cycle arrest followed by cell death. In conclusion, we have synthesised
      new anticancer agents that show selective cytotoxicity in colon cancer cells
      while remaining inactive in normal colon cells, and which mediate their effects
      via the G2/M phase of the cell cycle.

PMID- 12003184
TI  - Phase II trial of pegylated-liposomal doxorubicin (Doxil) in renal cell cancer.
AB  - Twelve patients with refractory renal cell cancer were treated on a phase II
      study of pegylated-liposomal doxorubicin (Doxil). The initial dose per course was
      55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot
      syndrome (the main limiting toxicities). Toxicities were mild and similar to
      previous reports but dose reduction per the study protocol, which was designed to
      control the skin and mucosal toxicities, was common. No definite cardiac toxicity
      was observed. No objective responses were observed in 11 evaluable patients. This
      study did not demonstrate activity of pegylated-liposomal doxorubicin in renal
      cell cancer, although it can be given with mild toxicity.

PMID- 12003185
TI  - A phase II trial of pyrazine diazohydroxide in patients with disseminated
      malignant melanoma and no prior chemotherapy--Southwest Oncology Group study.
AB  - Malignant melanoma is rapidly increasing in the United States. Metastatic disease
      responds poorly to currently available chemotherapy. Pyrazine diazohydroxide
      (PZDH) is a new agent inhibiting DNA synthesis that is active in mouse tumor
      models and human xenografts and lacks cross resistance with multiple standard
      agents. In this phase II trial, patients with no prior chemotherapy or
      immunotherapy for metastatic disease and performance status (SWOG) of 0-1, were
      treated with pyrazine diazohydroxide at a dose of 100 mg/m2/day by i.v. bolus
      injection over 5-15 minutes for 5 consecutive days every 6 weeks. There were 23
      eligible patients entered on this trial with 74% having PS of 0 and 91% having
      visceral metastases. There were no confirmed anti-tumor responses. The overall
      response rate is 0% (95% CI 0%-15%). Median overall survival is six months (95%
      CI 5-8 months). The most common toxicities were hematologic and consisted of
      lymphopenia, thrombocytopenia, anemia, and leukopenia. Fatigue. and nausea and
      vomiting were the next most common toxicities. Pyrazine diazohydroxide by this
      dose and schedule has insufficient activity in the treatment of disseminated
      malignant melanoma to warrant further investigation.

PMID- 12003186
TI  - Phase II trial of amonafide in central nervous system tumors: a Southwest
      Oncology Group study.
AB  - Amonafide 300 mg/M2 was administered intravenously on a daily x 5 schedule to 27
      eligible patients with recurrent or progressive central nervous system tumors.
      There were no objective responses. The most common toxicities were
      gastrointestinal, hematologic and neurologic. Further study of amonafide in
      patients with central nervous system malignancies is not indicated.

PMID- 12003187
TI  - The evaluation of gemcitabine in resistant or relapsing multiple myeloma, phase
      II: a Southwest Oncology Group study.
AB  - Gemcitabine is a cytosine arabinoside (Ara-C) analog with activity in many human
      tumor systems. We evaluated the drug's activity in resistant or relapsing
      multiple myeloma. Gemcitabine 1000 mg/m2 was administered as a 30 minute infusion
      on days 1, 8, and 15 of a 28-day cycle. No dose escalations were permitted and
      dose reductions were scheduled for hematologic toxicity. Twenty-nine eligible
      patients were entered into Southwest Oncology Group (SWOG)-9803. One patient
      received no treatment and 5 patients had inadequate response assessments. The
      major toxicity was hematologic with grade 3/4 neutropenia in 9 and grade 3/4
      thrombocytopenia in 15 patients. No responses were seen. Stable disease was
      confirmed in sixteen patients (57%). Median survival was eight months.
      Gemcitabine as utilized in this trial has shown little activity and is not to be
      strongly considered for future multiple myeloma trials.

PMID- 12003188
TI  - A phase II trial of bryostatin-1 in patients with metastatic or recurrent
      squamous cell carcinoma of the head and neck.
AB  - Bryostatin-1 is a macrocyclic lactone that has been shown to modulate Protein
      Kinase C activity and has demonstrated antitumor activity in vitro and in vivo.
      Fifteen patients with metastatic or recurrent squamous cell carcinoma of the head
      and neck were treated with bryostatin-1 at a dose of 25 mcg/m2 by continuous
      intravenous infusion over 24 hours once weekly for three weeks followed by a
      break week to complete a four-week cycle. There were no major objective responses
      in the 14 evaluable patients. One patient with nasopharynx cancer had disease
      stabilization for 4 months prior to being removed from the study due to medical
      issues. This clinical benefit corresponded to a radiographic decrease in
      metabolic activity on positron emission tomograpy (PET) scan as well as molecular
      evidence of tumor apoptosis in a poly[ADP-ribose] polymerase (PARP) cleavage
      assay. Bryostatin-1 is not recommended for use as a single agent for the
      treatment of squamous cell head and neck cancer. Further investigation is
      warranted to determine the strength of the correlation between bryostatin-1
      activity and PARP cleavage as a surrogate molecular marker of apoptosis.

PMID- 12003189
TI  - Phase II trial of topotecan by continuous infusion in patients with advanced soft
      tissue sarcomas, a SWOG study. Southwest Oncology Group.
AB  - PURPOSE: Based upon the hypothesis that prolonged exposure to the S-Phase
      specific agent topotecan would be more efficacious in the treatment of soft
      tissue sarcomas than a conventional 5-day schedule of the drug, the Southwest
      Oncology Group performed a Phase II trial of topotecan administered as a
      continuous infusion in adult patients with advanced soft tissue sarcomas.
      METHODS: Patients who had received no prior chemotherapy for advanced disease
      were treated with topotecan at a dose of 0.50 mg/m2/day on days 1-21 of repeated
      28 day cycles. RESULTS: Twenty-two patients were enrolled on the study, of whom
      21 were eligible. No objective responses were observed (95% confidence interval
      of 0-16%). The median survival was 12 months (95% confidence interval of 5-16
      months). CONCLUSIONS: We conclude that topotecan, given either according to a 5
      day or a 21-day schedule, has minimal activity in the treatment of adult soft
      tissue sarcomas.

PMID- 12003190
TI  - Preclinical efficacy evaluations of XK-469: dose schedule, route and cross
      resistance behavior in tumor bearing mice.
AB  - XK-469 is advancing to Phase I clinical trials. Preclinical studies were carried
      out to assist in clinical applications. DOSE-SCHEDULE ROUTE TESTING: Single dose
      i.v. treatment with XK-469 produced lethality (LD20 to LD100) above 142 mg/kg.
      Optimum treatment required total dosages of 350 to 600 mg/kg. Furthermore, high
      individual i.v. dosages (100 to 142 mg/kg) were poorly tolerated, producing
      substantial weight loss (8 to 18% of body weight), poor appearance, and slow
      recovery (8 to 12 days). A 1-hour infusion of dosages more than 140 mg/kg, or BID
      injections 6 hrs apart, did not reduce lethality. However, lower individual
      dosages of 40 to 50 mg/kg/injection i.v. were well tolerated and could be given
      daily to reach an optimum total dose with minimal toxicities. Likewise, 75
      mg/kg/injection i.v. could be used every other day to reach optimal treatment.
      The necropsy profiles of deaths from toxic dosages were essentially identical
      regardless of schedule (deaths 4 to 7 days post treatment). The profiles were:
      paralytic ileus or gastroparesis; GI epithelial damage; and marrow toxicity.
      Interestingly, the key lethal events were rapidly reversible and simple to
      overcome with lower dosages given daily or every other day. Based on these
      results, the high dose, Q21 day schedule should be avoided in clinical
      applications. Instead, a split dose regimen is recommended (e.g., daily, every
      other day, or twice weekly). XK-469 was also well tolerated by the oral route,
      requiring 35% higher dosages p.o. to reach the same efficacy and toxicity as
      produced i.v.. CROSS-RESISTANCE STUDIES: XK-469 resistance was produced by
      optimum treatments of i.v. implanted L1210 leukemia over seven passage
      generations. This leukemia subline (L1210/XK469) had reduced sensitivity to VP-16
      (with a 4.0 log kill in i.v. implanted L1210/XK469 compared to an 8.0 log kill
      against i.v. implanted L1210/0). It also had a reduction in the sensitivity to 5
      FU (with a 2.0 log kill in the implanted L1210/XK469 compared to a 4.0 log kill
      against i.v. implanted L1210/0). Other agents were approximately as active
      against the resistant tumor, including: Ara-C, Gemzar, Cytoxan, BCNU, DTIC, and
      CisDDPT. No case of collateral sensitivity was observed; i.e., no agent was
      markedly more active against the resistant subline L1210/XK-469 than against the
      parent tumor in mice.

PMID- 12003191
TI  - Raltitrexed (tomudex) administration in patients failing multiple prior
      chemotherapy regimens in advanced colorectal cancer: a pilot study.
AB  - PURPOSE: To evaluate efficacy of Raltitrexed, a specific thymidilate synthase
      inhibitor, in patients with advanced colorectal cancer (ACC) failing multiple
      prior chemotherapy regimens (e.g. 5-FU+LV, CPT-11, etc). METHODS: 20 patients
      with ACC; 13 males/7 females, median age 64 (range: 53-69), median Karnovsky PS:
      80 (70-90), and sites of metastases; liver: 16, lung: 6, lymph nodes: 9,
      peritoneal: 8 and a life expectancy of at least 3 months, were entered in the
      present pilot study of Raltitrexed administration. All patients had progressed
      after prior chemotherapy with 5-FU+LV and subsequently CPT-11, and some had
      received further infusional 5-FU, Raltitrexed was administered at a dose of 3
      mg/m2 i.v. every 21 days. RESULTS: 3 patients obtained stable disease (SID), 15%,
      with tumor marker decline (CEA, CA-19.9). Time-to-progression was 4.8 months (2.2
      7) and survival 7.4 months (6.0-7.8). Toxicity was in general not severe and
      consisted mainly of myelosuppression; neutropenia (WHO) grade 2: 45% and grade 3:
      22%, and anemia grade 1-2: 40%. CONCLUSION: Response to treatment with
      Raltitrexed is limited in patients with ACC failing multiple prior chemotherapy
      regimens, however, a limited percentage of patients with SD derived clinical
      benefit.

PMID- 12003192
TI  - Lack of in vitro-in vivo correlation of a novel investigational anticancer agent,
      SH 30.
AB  - In solid tumors, the reasons for the lack of in vitro and in vivo correlation of
      drug activities are multifold and includes permeability to the tumor cells,
      interstitial hypertension and metabolic degradation. So, it is important to study
      the permeability and metabolic disposition of new compounds early in discovery
      and development of anticancer drugs. An experimental anti-cancer drug, SH 30
      demonstrated highly selective and potent cytotoxic activity against a number of
      multi-drug resistant tumor cell lines in vitro. However, it was inactive in a
      murine tumor model. This study was conducted to identify the barriers that result
      in lack of correlation between in vitro and in vivo cytotoxic activity of novel
      anticancer agents. Two important barriers: physical (permeability) and metabolic
      (enzymatic inactivation) to poor delivery of SH 30 to solid tumors were
      investigated in this study. Tumors were sliced to separate the vascular and
      avascular sections. The concentrations of the drug at various regions of the
      tumor after single and multiple doses were investigated to determine the
      permeability barrier. The permeability barrier was also probed using two in vitro
      model systems, namely, matrigel films representing extracellular matrix and caco
      2 multilayer cell cultures that simulate solid tumors. The drug and its
      metabolite concentrations were determined in the plasma and tumors to determine
      the metabolic barrier to the drug cytotoxic action. The metabolic barrier was
      further probed using in vitro mouse hepatocytes and liver microsome preparations.
      Our examination revealed the metabolic barrier to be the major contributor to the
      ineffectiveness of SH 30 in vivo. Examination of concentration of the drug across
      various regions of the tumor corroborated by data from in vitro permeation
      studies suggested that, for SH 30, permeability barrier did not exist. After
      single injection, the concentrations of SH 30 and its metabolites in plasma and
      tumor were comparable to another investigational drug with similar features (XK
      469). Contrary to day 1, after 8 consecutive days of administration, SH 30
      concentrations were significantly lower, while the metabolites concentrations
      were higher, suggesting extensive metabolism due to induction of enzyme(s). The
      in vitro hepatocytes and liver microsome results also showed SH 30
      biotransformation to the same metabolites. Neither drug penetration, nor drug
      distribution into regions of the tumors distal to vasculature were impeded. The
      inactivity of SH 30 in vivo is primarily due to induction of extensive metabolism
      to inactive metabolites. This metabolism prevents adequate drug levels being
      achieved in the tumor.

PMID- 12003193
TI  - Partial circumvention of P-glycoprotein-mediated multidrug resistance by
      doxorubicin-14-O-hemiadipate.
AB  - Previously, we have reported partial circumvention of P-glycoprotein (Pgp)
      associated resistance to doxorubicin (Dox) in MCF7/R human breast carcinoma and
      P388/R murine leukemia cell lines by doxorubicin-14-O-hemiadipate (H-Dox)
      [Povarov L.S. et al. (1995) Russian J. Bioorganic Chemistry 21: 797-803]. We felt
      that these changes were due to alterations in the cellular pharmacokinetics of
      the analog in multidrug (MDR) resistant cells, as compared to that of Dox. To
      address this hypothesis, we performed comparative studies of the accumulation,
      retention and intracellular localization of H-Dox and Dox in Dox-sensitive murine
      leukemia cell line P388/S and its Dox-selected. Pgp-positive drug resistant
      P388/R subline. These studies were performed in the presence or absence of
      cyclosporin A (CsA), a competitive inhibitor of Pgp. Flow cytometric analysis
      revealed significant differences in Dox and H-Dox accumulation in P388/R cells
      when compared to P388/S cells. In P388/R versus P388/S cells, there was a 38-fold
      decrease in Dox accumulation, but only a 5-fold decrease in H-Dox accumulation,
      indicating over a 7-fold increase in H-Dox buildup in resistant cells. CsA did
      not affect uptake or retention of either drug by sensitive cells. However,
      coincubation with CsA resulted in a 54-fold increase in Dox accumulation and only
      a 5-fold increase in H-Dox uptake in P388/R cells, restoring anthracycline levels
      in P388/R to 100% of that found in P388/S cells. Once internalized by the
      resistant cells, H-Dox was retained better than Dox regardless of presence or
      absence of CsA. Confocal microscopic analysis revealed the presence of H-Dox but
      no Dox in cellular nuclei of P388/R cells. Thus, increased activity of H-Dox
      toward P388/R cells was correlated with its enhanced ability to enter and be
      retained in these cells, and also with redistribution of H-Dox into the nuclei of
      the resistant cells as compared to Dox. Overall, our findings support our initial
      hypothesis and provide evidence that H-Dox, a 14-O-hemiadipate of doxorubicin, is
      affected by Pgp-mediated MDR to a lesser extent than parental Dox due to changes
      iin the cellular pharmacokinetics of the analog.

PMID- 12003194
TI  - Chemotherapy-induced palmar-plantar erythrodysesthesia syndrome--recall following
      different chemotherapy agents.
AB  - Radiation recall is a phenomenon commonly seen in patients receiving chemotherapy
      treatment who have previously been exposed to radiation. A phenomenon not clearly
      described is that of a side effect induced by one chemotherapy agent and later
      recalled when the patient is given a different chemotherapy regimen.
      Troxacitabine is an anti-leukemic agent which can be associated with palmar
      plantar erythrodysesthesia syndrome (PPES). Here, we report six cases of
      troxacitabine-induced PPES that was later recalled by various chemotherapy
      regimens. The recall PPES was mild to moderate and self-limiting in all cases.
      All of these patients recovered from the recall side effects with minimal medical
      intervention. We conclude that a recall phenomenon similar to that described
      after radiotherapy might occur after certain chemotherapy agents. This phenomenon
      should be considered when evaluating toxicity from chemotherapy, particularly
      when using new and investigational agents.

PMID- 12003195
TI  - Phase I clinical trial of 5-fluoro-pyrimidinone (5FP), an oral prodrug of 5
      fluorouracil (5FU).
AB  - PURPOSE: 5-Fluoro-Pyrimidinone (5FP) is an oral pro-drug of 5-Fluorouracil (5FU),
      and is converted to 5FU by hepatic aldehyde oxidase. Preclinically, 5FP
      demonstrated anti-tumor activity against colon 38 and P 388 leukemia models in
      mice. Using an accelerated titration trial design with one patient cohorts and
      initial 100% escalations, a Phase I trial was conducted to determine the maximum
      tolerated dose (MTD) of 5FP and describe its toxicity and pharmacokinetic
      profile. PATIENTS AND METHODS: 5FP was administered orally once daily for 5 days
      every 4 weeks. The initial dose level was 23 mg/m2/d. Using single patient
      cohorts, escalation proceeded according to accelerated titration 4B design,
      initially by 100% and subsequently 30-35% escalations (exact escalation
      determined by pill size) until dose limiting toxicity was observed. A total of 19
      patients were enrolled with a median age of 56 years and median performance
      status of 1. Most patients were heavily pre-treated with chemotherapy, radiation
      therapy, or both, and patient population included a wide variety of tumor types.
      RESULTS: Dose escalation proceeded rapidly to 1715 mg/m2/d with the only
      toxicities observed being nausea and vomiting. The large number of pills
      necessary at that point required a formulation change, which resulted in
      appreciable hematologic toxicity. This led to rapid de-escalation of dose in
      subsequent patients, with the MTD finally being determined to be 625 mg/m2/d. The
      DLTs observed were grade 4 neutropenia for greater than 5 days and grade 3
      anemia. Other toxicities included nausea, vomiting, fatigue, constipation and
      mucositis. Pharmacology studies confirmed that SFP was converted to 5FU in humans
      at all dose levels. However, the extent of conversion decreased over the five
      daily treatments, but returned for the subsequent cycle. The hematologic toxicity
      was not related to 5FU exposure per course. CONCLUSION: 5FP is a tolerable oral
      outpatient therapy. Accelerated titration was an efficient way of conducting this
      phase I trial. The recommended phase 2 dose is 625 mg/m2/d orally for 5 days
      every 28 days.

PMID- 12003196
TI  - Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer.
AB  - BACKGROUND: Because gemcitabine and vinorelbine have demonstrated single-agent
      activity in non-small cell lung cancer (NSCLC), we conducted this phase I/II
      study to determine the maximum tolerated dose (MTD) and activity of these drugs
      combined. PATIENTS AND METHODS: Patients with inoperable or advanced NSCLC and no
      prior chemotherapy were treated with gemcitabine plus vinorelbine on days 1 and 8
      every 21 days. The initial doses of gemcitabine 1,000 mg/m2 and vinorelbine 25
      mg/m2 were escalated by 250 mg/m2 and 5 mg/m2, respectively, in separate patient
      cohorts until the MTD was established. RESULTS: In phase I, 32 patients received
      a total of 115 cycles. Dose-limiting toxicities were neutropenia and
      hepatotoxicity, occurring at the dose level of 1,500 mg/m2 and 30 mg/m2. Thus,
      the MTD used for phase II was 1,250 mg/m2 and 30 mg/m2. Of 41 patients in phase
      II, 16 (39%) achieved objective responses (95% confidence interval [CI] 24% to
      54%), with a median time to progression of 4.2 months. Overall survival was 9
      months (95% CI 5.7 to 12.7 months) and the 1-year survival rate was 31%. World
      Health Organization (WHO) > or = grade 3 neutropenia and reversible
      thrombocytosis occurred in 15% and 65% of patients, respectively. Non-hematologic
      toxicity was mild at all dose levels. Grades 3 and 4 hepatotoxicity were reported
      in one patient each. CONCLUSION: The combination of 1,250 mg/m2 gemcitabine and
      30 mg/m2 vinorelbine on days 1 and 8 every 21 days is well tolerated and active
      in patients with NSCLC. These results should be confirmed in comparative studies.

PMID- 12003197
TI  - Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor
      lurtotecan in phase II studies.
AB  - Population pharmacokinetic-dynamic analysis was prospectively integrated in a
      broad phase II program of lurtotecan (GI147211), a novel camptothecin derived
      topoisomerase I inhibitor, to determine the population pharmacokinetic profile in
      a larger population, to estimate individual pharmacokinetic parameters and to
      investigate relationships with clinical outcome. A sparse sampling method was
      applied during course one, which involved two sampling time-points. A Bayesian
      algorithm was used to estimate individual pharmacokinetic parameters, in
      particular total plasma clearance (CL) and volume of distribution. In total,
      samples were collected of 109 (63%) of 173 patients. Pharmacokinetic-dynamic
      evaluation could be carried out successfully in 85 (78%) of the sampled patients.
      CL of lurtotecan showed substantial variability (mean 87 +/- 28 L/h) and was of
      the same magnitude as in the phase I studies where full pharmacokinetic curves
      were used. Residual variability in the population estimate of CL was 9.9%. No
      significant relationships were observed between exposure parameters and toxicity
      nor likelihood of tumor response, however the latter relationship may well have
      been obscured by the heterogeneity of the studied population. Prospective
      implementation of large scale population pharmacokinetic-dynamic analysis is
      feasible and important to establish whether interpatient variability in drug
      exposure is a major determinant of toxicity or activity.

PMID- 12003198
TI  - Phase II trial of docetaxel chemotherapy in patients with incurable
      adenocarcinoma of the esophagus.
AB  - BACKGROUND: Chemotherapy remains the primary mode of treatment for metastatic
      carcinoma of the esophagus. The efficacy of various chemotherapeutic regimens has
      been studied predominantly in patients with squamous cell carcinoma of the
      esophagus. In light of the increasing incidence of adenocarcinoma of the
      esophagus, studies evaluating newer chemotherapy agents, such as docetaxel, in
      this patient population are necessary. The objective of this trial was to
      determine the complete and partial response rate of docetaxel in patients with
      incurable adenocarcinoma of the esophagus. PATIENTS AND METHODS: Eligible
      patients had histologically confirmed metastatic adenocarcinoma of the esophagus
      or locally extensive disease not curable with surgery or radiation therapy.
      Patients were either chemotherapy naive or previously treated with chemotherapy
      (including paclitaxel). Docetaxel was administered at a dose of 75 mg/m2 every
      three weeks intravenously. Appropriate imaging studies/examinations were obtained
      after every two cycles to evaluate response. RESULTS: A total of 22 patients were
      enrolled in the trial. Chemotherapy-naive patients achieved a response rate of
      18% (95% CI = 2.3 to 51.8) while patients who received prior chemotherapy
      achieved a 0% response rate (95% CI = 0 to 25). There were no complete responses.
      The overall median survival time is 3.4 months and the one-year survival rate is
      21%. The toxicities included febrile neutropenia (32%) as well as grade 3 and 4
      fatigue (14%) and anorexia (9%). CONCLUSIONS: Although chemotherapy naive
      patients achieved an 18% response rate and no responses were seen in previously
      treated patients, the limitations of this trial does not allow for any definitive
      conclusions to be made about the efficacy of single agent docetaxel chemotherapy
      in patients with incurable esophageal cancer.

PMID- 12003199
TI  - Sensing wave-front amplitude and phase with phase diversity.
AB  - We show in benchtop experiments that wave-front phase estimation by phase
      diversity can be significantly improved by simultaneous amplitude estimation.
      Processing speed, which will be important for real-time wave-front control
      applications, can be enhanced by use of small-format detectors with pixels that
      do not fully sample the diffraction limit. Using an object-independent phase
      diversity algorithm, we show that, for both pointlike and extended objects, the
      fidelity of the phase and amplitude estimates degrades gracefully, rather than
      catastrophically, as the sampling becomes coarser. We show in simulation that the
      same algorithm also improves the fidelity of image reconstruction of complex
      targets.

PMID- 12003200
TI  - Reverse phase contrast: an experimental demonstration.
AB  - We present experimental results showing that the reverse phase contrast (RPC)
      technique is a viable method for the generation of a binary phase distribution
      from a spatially varying amplitude pattern using Fourier plane filtering
      techniques. Experimental results are shown for the generation of a binary 0-pi
      phase only distribution using either an amplitude mask or a spatial light
      modulator to provide the input and the results are shown to be in agreement with
      theoretical predictions for the RPC technique.

PMID- 12003201
TI  - Full geometry dependence of index contrast in photorefractive polymer composites.
AB  - Detailed analysis of the relationship between the experimental geometry and the
      holographic contrast in photorefractive polymers is important for applications,
      such as angle multiplexing in holographic data storage. In this paper the field
      dependent photogeneration efficiency is introduced into the complete
      reorientational model to provide a full account of the electric field and
      geometrical dependence of the index contrast. The interaction of a local grating
      and the photorefractive grating is also considered. A simplification for acute
      angles between writing beams is described. Experimental verification by use of
      four-wave mixing and transmission ellipsometry reveals an excellent agreement
      between theory and measurement.

PMID- 12003202
TI  - Holographic generalized first-arriving light approach for resolving images viewed
      through a scattering medium.
AB  - We present a generalized holography-based approach with improved spatial
      resolution for extracting images, viewed through a scattering medium. The various
      angular directions are encoded either with different wavelengths or by capturing
      their corresponding images in different time slots. The various encoded images
      are recorded on a digital hologram with a computer. A digital reconstruction,
      which includes demodulation of the carrier beam and then a proper decoding
      algorithm, yields resolved images. The principle is demonstrated by recording
      image-plane digital holograms. Combining the suggested approach with the first
      arriving light technique may further improve the results.

PMID- 12003203
TI  - Polarization gratings with surface relief in dyed gelatin and their
      postdevelopment diffraction.
AB  - Some characteristics of dyed gelatin films when polarization gratings are
      recorded are reported. Two dyes, Malachite Green and Methylene Blue, are used in
      our experiment. In particular, no dichromate was added to Methylene Blue plates
      before or after exposure. It is shown that, in spite of its having high
      viscosity, a relief grating is formed when orthogonal linearly polarized beams
      are superimposed upon the plates. In contrast with previous observations in
      another photoanisotropic medium, the frequency of the gelatin relief grating does
      not depend on the directions of the electric field of the orthogonal recording
      beams. Besides, when orthogonal circularly polarized beams are used in the
      formation of polarization gratings, no relief grating is produced. Finally, we
      study the phase modulation obtained after dehydration of the gelatin plates in
      which the polarization gratings were formed. Postdevelopment phase gratings do
      not preserve the polarization information of the interference pattern. Also, the
      grating frequency is increased by a factor of 2 for linear polarization, whereas
      for circular polarization there is no phase modulation.

PMID- 12003204
TI  - Least-mean-squares phase unwrapping by use of an incomplete set of residue branch
      cuts.
AB  - A new technique for the least-mean-squares (LMS) phase-unwrapping method is
      developed that incorporates the concept of branch cuts between phase
      singularities (residues), which are usually associated with the path-following
      gradient integration technique. These branch cuts are introduced by decomposition
      of the least-mean-squares unwrapped phase into two separate components. The first
      results from the transverse part of the wrapped phase gradient, which is induced
      by residues of the original phase, and the second component is due to a potential
      component, independent of the residues. This decomposition allows the
      reconstruction of phase patterns with a high level of accuracy and consistency
      with the initial (wrapped) phase, even when only partial knowledge of the
      placement of branch cuts between residues is available. We show how the residue
      induced phase, ignored by conventional LMS phase estimators, is reconstructed for
      a given boundary-value problem. The method is illustrated with interferometric
      quality-control measurements of optical fiber-connector terminations and also
      with synthetic aperture radar interferometry. These experiments demonstrate the
      high accuracy of the method in practical situations in which only a limited
      number of branch cuts are available.

PMID- 12003205
TI  - Distortion tolerant image recognition receiver by use of a multiple-hypothesis
      method.
AB  - A multiple-hypothesis method is used to detect a target or a reference signal in
      the presence of additive noise with unknown statistics. The receiver is designed
      to detect the target and to be tolerant of the variations in rotation and
      illumination of the target. A multiple-hypothesis test with unknown-noise
      parameters is used to locate the target position. The proposed method does not
      use any specific distortion-invariant-filtering technique, but it relies on a
      multiple-hypothesis approach. Maximum-likelihood estimates of the illumination
      constant and the unknown noise parameters are obtained. Computer simulations are
      presented to evaluate the performance of the receiver for various distorted noisy
      true-class targets with varying illumination and false-class objects.

PMID- 12003206
TI  - New approach for enlargement of medical electronic endoscopic images.
AB  - To compensate for the imperfections of the endoscopic mechanical structure and
      the limitations of working space, a new technology based on the recursive
      minimum/maximum method is proposed to enlarge images obtained by the medical
      electronic endoscope. This method can be used repeatedly to obtain image
      enlargement to 2x by optimizing the neighborhood information of the pixels of
      interest in adjustable windows. In order to ensure the best evaluation of the
      pixel, the algorithm criterion is presented to decide whether the new gray value
      is assigned to the pixel. Experimental results from enlarged endoscopic images
      are presented that demonstrate that the recursive minimum/maximum method for
      image enlargement can preserve the fine details with rich edge information and
      with better visualization.

PMID- 12003207
TI  - Recognition of motion-blurred images by use of the method of moments.
AB  - Image motion causes a blur that changes features of objects and therefore
      complicates the task of automatic recognition. In this work we develop two
      recognition methods for motion-blurred images. For the first method we assume
      that the motion function and direction during the exposure are given. We develop
      the relation between the blurred-image moments and the original-image moments
      based on the motion function only. The recognition is carried out by comparing
      the moments of the restored image against the moments of the image database. In
      the second method the motion function is not known. In this case image moments
      that are invariant with respect to the motion blur are identified, and only these
      moments are used for recognition. The advantage of the suggested methods is that
      no time-consuming image restoration is required prior to recognition.

PMID- 12003208
TI  - Optimum nonlinear composite filter for distortion-tolerant pattern recognition.
AB  - We describe a nonlinear distortion-tolerant filter for pattern recognition that
      is optimum in terms of tolerance to input noise and discrimination capability.
      This filter was derived by minimization of the output energy that is due to the
      overlapping additive noise and the input scene, and the output of the filter
      meets the design constraints obtained from the training data set. The performance
      of this filter was tested with an input scene containing one of the training data
      sets, a nontraining true target, and a false object in the presence of
      overlapping additive noise and nonoverlapping background noise. We carried out
      Monte Carlo runs to measure the statistical performance of the filter and
      obtained receiver operating characteristics curves to show the detection
      capabilities of the filter.

PMID- 12003209
TI  - High-speed, high-sensitivity, gated surface profiling with closed-loop optical
      coherence topography.
AB  - We describe and experimentally demonstrate a novel (to our knowledge) surface
      profiling technique, for which we propose the term closed-loop optical coherence
      topography. This technique is a scanning beam, servo-locked variation of low
      coherence interferometry. It allows for the sub-wavelength-resolution tracking of
      a weakly scattering macroscopic-scale surface, with the surface profile being
      directly output by the controlling electronics. The absence of significant real
      time computational overhead makes the technique well suited to high-speed
      tracking. The use of a micrometer-scale coherence gate efficiently suppresses
      signals arising from structures not associated with the surface. These features
      make the technique particularly well suited to real-time surface profiling of in
      vivo, macroscopic biological surfaces.

PMID- 12003210
TI  - Effect of spectral band numbers on the retrieval of water column and bottom
      properties from ocean color data.
AB  - Using an optimization technique, we derived subsurface properties of coastal and
      oceanic waters from measured remote-sensing reflectance spectra. These data
      included both optically deep and shallow environments. The measured reflectance
      covered a spectral range from 400 to 800 nm. The inversions used data from each 5
      , 10-, and 20-nm contiguous bands, including Sea-viewing Wide Field-of-view
      Sensor (SeaWiFS), moderate-resolution imaging spectrometer (MODIS), and a self
      defined medium-resolution imaging spectrometer (MERIS) channels, respectively.
      This study is designed to evaluate the influence of spectral resolution and
      channel placement on the accuracy of remote-sensing retrievals and to provide
      guidance for future sensor design. From the results of this study, we found the
      following: (1) use of 10-nm-wide contiguous channels provides almost identical
      results as found for 5-nm contiguous channels; (2) use of 20-nm contiguous
      channels and MERIS provides comparable results with those with 5-nm contiguous
      channels for deep waters, but use of contiguous 20-nm channels perform better
      than MERIS for optically shallow waters; and (3) SeaWiFS or MODIS channels work
      fine for deep, clearer waters (total absorption coefficient at 440 nm < 0.3 m(
      1)), but introduce more errors in bathymetry retrievals for optically shallow
      waters. The inclusion of the 645-nm MODIS land band in its channel set improves
      inversion returns for both deep and shallow waters.

PMID- 12003211
TI  - Role of oceanic air bubbles in atmospheric correction of ocean color imagery.
AB  - Ocean color is the radiance that emanates from the ocean because of scattering by
      chlorophyll pigments and particles of organic and inorganic origin. Air bubbles
      in the ocean also scatter light and thus contribute to the water-leaving
      radiance. This additional water-leaving radiance that is due to oceanic air
      bubbles could violate the black pixel assumption at near-infrared wavelengths and
      be attributed to chlorophyll in the visible. Hence, the accuracy of the
      atmospheric correction required for the retrieval of ocean color from satellite
      measurements is impaired. A comprehensive radiative transfer code for the coupled
      atmosphere--ocean system is employed to assess the effect of oceanic air bubbles
      on atmospheric correction of ocean color imagery. This effect is found to depend
      on the wavelength-dependent optical properties of oceanic air bubbles as well as
      atmospheric aerosols.

PMID- 12003212
TI  - Convergence rates for iterative vector space projection methods for control of
      two deformable mirrors for compensation of both amplitude and phase fluctuations.
AB  - The control of two deformable mirrors for compensation of time-varying
      fluctuations in the complex field that results from wave propagation through a
      turbulent medium is considered. Iterative vector space projection methods are
      utilized to determine the control commands to be applied to the two deformable
      mirrors. Convergence of the iterative algorithm is accelerated when the algorithm
      is initialized, at each measurement period, with the values for the phase
      commands obtained from the previous measurement period. Furthermore, it is found
      that, if the sample frequency is sufficiently greater than the Greenwood
      frequency, then only a single iterative step at each measurement period is
      required to obtain good compensation of both amplitude and phase fluctuations.

PMID- 12003213
TI  - Wave-front tilt sensor with two quadrant detectors and its application to a laser
      beam pointing system.
AB  - A method that uses two quadrant detectors (QDs) for sensing wave-front tilt is
      described. The detectors are set at the front and back of the focal plane of the
      focusing optics. When the intensity distribution at the aperture of a telescope
      is not uniform because of atmospheric turbulence, the wave-front tilt can be
      measured more accurately with our two-QD method than with a conventional single
      focal-plane QD. We proved this method to be effective by using it for fixed-star
      observation. Application of the method to a ground-to-satellite laser beam
      pointing system showed that it increases the intensity of the laser beam that is
      transmitted to a satellite.

PMID- 12003214
TI  - Irradiance inversion algorithm for absorption and backscattering profiles in
      natural waters: improvement for clear waters.
AB  - Our iterative inversion algorithm for retrieving absorption a(z) and
      backscattering b(b)(z) from profiles of upwelling and downwelling irradiance, on
      the basis of assuming a depth-independent phase function for the medium, was
      found to have unsatisfactory accuracy for b(b)(z) in clear waters. We modified
      the algorithm here by assuming a depth-independent phase function for the
      particles and then performing an additional iteration over the fraction of total
      scattering that is due to the water itself. The modified algorithm's accuracy is
      considerably improved over the original in clear waters and reduces to the
      original in waters for which the particle contribution to b(b)(z) is dominant.

PMID- 12003215
TI  - Low-temperature-GaAs device used simultaneously as a mode-locking device and as a
      photoconductive switch.
AB  - We present a low-temperature-grown GaAs device that combines the features of mode
      locking and photoconductive switching. The mode-locking mechanism is based on
      intensity-dependent defocusing. Additionally, the generated carriers produce an
      electrical signal in the biased switch geometry. This technique allows for
      simultaneous generation of synchronized optical and electrical pulse trains with
      a single device.

PMID- 12003216
TI  - Effectiveness of simultaneous independent realizations at low carrier-to-noise
      ratio to improve heterodyne Doppler lidar performance. I. Theory and numerical
      simulations.
AB  - It is shown that the performance of heterodyne Doppler lidar (HDL) can be
      improved by (i) at least one good realization for every single shot or (ii)
      several simultaneous good realizations for accumulation. Until now, several
      simultaneous independent realizations at high carrier-to-noise ratio (CNR) have
      been considered. At low CNR, noise may have a detrimental effect on the
      accumulation techniques. We determine the chances of getting "heavy" speckles in
      HDL signals from many receiver-detector units on a single-shot basis and several
      good realizations on a single-shot basis, which is required for an effective
      accumulation. The use of multiple receiver-detector units at low CNR is
      worthwhile in contexts such as space lidar, where optimized treatment is at a
      premium. We conclude on the effectiveness of many receiver-detector units in
      parallel in order to achieve simultaneous independent realizations at low CNR to
      improve the performance of HDL on a statistical basis.

PMID- 12003217
TI  - Effect of periodic background loss on grating spectra.
AB  - The effect of periodic loss on the performance of refractive-index gratings has
      been studied in detail. It is shown that the loss periodicity and relative phase
      strongly affects the symmetry of the reflection, transmission, and loss spectra.
      This asymmetry is explained successfully through consideration of the overlap
      between the standing-wave intensity distribution and the periodic loss pattern.

PMID- 12003218
TI  - Space-bandwidth product enhancement of a monostatic, multiaperture infrared image
      upconversion ladar receiver incorporating periodically poled liNbO3.
AB  - We investigate the space-bandwidth product of a ladar system incorporating an
      upconversion receiver. After illuminating a target with an eye-safe beam, we
      direct the return into a piece of periodically poled LiNbO3 where it is
      upconverted into the visible spectrum and detected with a CCD camera. The
      theoretical and experimental transfer functions are then found. We show that the
      angular acceptance of the upconversion process severely limits the receiver field
      of regard for macroscopic coupling optics. This limitation is overcome with a
      pair of microlens arrays, and a 43% increase in the system's measured space
      bandwidth product is demonstrated.

PMID- 12003219
TI  - Optimized differential absorption radiometer for remote sensing of chemical
      effluents.
AB  - A differential absorption radiometer sensor that was optimized for near-perfect
      (to approximately 2%) correction of the absorption by ambient atmospheric species
      (e.g., water) is described. A target gas is detected remotely by its IR signature
      viewed through a bandpass filter centered at one of its strongest lines. A second
      radiometric measurement obtained through a bandpass filter centered at a
      frequency optimized to match the absorption by an atmospheric trace species
      (e.g., water vapor) at the sample filter frequency provides near-perfect
      correction for dominant background absorption effects. The net absorption
      (emission) by the target gas was obtained through subtraction of the reference
      signal of the second measurement from that of the target gas measurement. For
      multiple species detection, additional sample and reference filter pairs can be
      configured. Predictions show that detection of strong absorbers such as dimethyl
      methylphosphonate at an optical density below 100 mg/m2 is possible from
      distances of < 6 km.

PMID- 12003220
TI  - H2O absorption spectroscopy for determination of temperature and H2O mole
      fraction in high-temperature particle synthesis systems.
AB  - Water absorption spectroscopy has been successfully demonstrated as a sensitive
      and accurate means for in situ determination of temperature and H2O mole fraction
      in silica (SiO2) particle-forming flames. Frequency modulation of near-infrared
      emission from a semiconductor diode laser was used to obtain multiple line-shape
      profiles of H2O rovibrational (v1 + v3) transitions in the 7170-7185-cm(-1)
      region. Temperature was determined by the relative peak height ratios, and XH2O
      was determined by use of the line-shape profiles. Measurements were made in the
      multiphase regions of silane/hydrogen/oxygen/ argon flames to verify the
      applicability of the diagnostic approach to combustion synthesis systems with
      high particle loadings. A range of equivalence ratios was studied (phi = 0.47 -
      2.15). The results were compared with flames where no silane was present and with
      adiabatic equilibrium calculations. The spectroscopic results for temperature
      were in good agreement with thermocouple measurements, and the qualitative trends
      as a function of the equivalence ratio were in good agreement with the
      equilibrium predictions. The determinations for water mole fraction were in good
      agreement with theoretical predictions but were sensitive to the spectroscopic
      model parameters used to describe collisional broadening. Water absorption
      spectroscopy has substantial potential as a valuable and practical technology for
      both research and production combustion synthesis facilities.

PMID- 12003221
TI  - Simultaneous measurement of one- and two-photon excited fluorescence from a
      single sample: a detection method for oligonucleotides.
AB  - A new method has been developed that is based on the use of a single-excitation
      wavelength from a cw laser to excite simultaneously one-photon and two-photon
      fluorescence (TPF). Fluorescence bands of a sample containing two
      oligonucleotides, one labeled with a one-photon fluorescence dye and the other
      with a TPF dye, can be measured simultaneously. The two fluorescence bands are
      well separated, because the one-photon excited fluorescence band is redshifted,
      whereas the TPF band is blueshifted from the excitation wavelength. The spectral
      separation was found to be as large as 200 nm when ADS 840NCS was used to label
      one oligonucleotide for one-photon fluorescence and Rhodamine Red-X dye was used
      for TPF. Spectral overlapping problem that plagues current DNA sequencing
      techniques can be eliminated effectively with this method.

PMID- 12003222
TI  - Refractive index of air: 3. The roles of CO2, H2O, and refractivity virials.
AB  - The author's recent studies of the refractive index of air are extended, and
      several assumptions made therein are further examined. It is shown that the
      alternative dispersion equations for CO2, which are due to Edlen [Metrologia 2,
      71 (1966)] and Old et al. [J. Opt. Soc. Am. 61, 89 (1971)] result in differences
      of less than 2 x 10(-9) in the phase refractive index and less than 3 x 10(-9) in
      the group refractive index for current and predicted concentrations of CO2.
      However, because the dispersion equation given by Old et al. is consistent with
      experimental data in the near infrared, it is preferable to the equation used by
      Edlen, which is valid only in the ultraviolet and the visible. The classical
      measurement by Barrell and Sears [Philos. Trans. R. Soc. London Ser. A 238, 1
      (1939)] on the refractivity of moist air is shown to have some procedural errors
      in addition to the one discussed by Birch and Downs [Metrologia 30, 155 (1993)].
      It is shown that for normal atmospheric conditions the higher refractivity virial
      coefficients related to the Lorentz-Lorenz relation are adequately incorporated
      into the empirically determined first refractivity virial. As a guide to users
      the practical limits to the calculation of the refractive index of the atmosphere
      that result from the uncertainties in the measurement of the various atmospheric
      parameters are summarized.

PMID- 12003223
TI  - Temperature and pulse-duration dependence of second-harmonic generation in
      CdGeAs2.
AB  - A detailed investigation of frequency doubling of a transversely excited
      atmospheric CO2 laser operating at 9.55 microm with a CdGeAs2 crystal was carried
      out. The temperature of the crystal was varied between 80 and 295 K to maximize
      the frequency-doubled energy. The temporal shape of the generated beam at 4.775
      microm was monitored to calculate its peak power. High values of midwave infrared
      pulse energy (16.65 mJ) and peak power (92 kW) were obtained, which can be of
      potential use in lidar systems.

PMID- 12003224
TI  - Application of an all-solid-state, frequency-doubled Nd:YAP laser to the
      generation of twin beams at 1080 nm.
AB  - A laser-diode-pumped intracavity frequency-doubled Nd:YAP/KTP laser is presented.
      Over 110 mw of TEM00 single-frequency output power at 540-nm wavelength was
      obtained. The output green laser was employed to pump a semimonolithic
      nondegenerate optical parametric oscillator to produce intensity quantum
      correlated twin beams at 1080 nm, and the maximum quantum noise squeezing of 74%
      (5.9dB) on the intensity difference fluctuation between the twin beams is
      observed. The threshold was reduced and the stability was increased significantly
      when compared with similar lamp-pumped systems.

PMID- 12003225
TI  - Femtosecond snapshot imaging of propagating light itself.
AB  - An ultrafast imaging technique has been developed to visualize directly a light
      pulse that is propagating in a medium. The method, called femtosecond time
      resolved optical polarigraphy (FTOP), senses instantaneous changes in the
      birefringence within the medium that are induced by the propagation of an intense
      light. A snapshot sequence composed of each femtosecond probing the pulse delay
      enables ultrafast propagation dynamics of the intense femtosecond laser pulse in
      the medium, such as gases and liquids, to be visualized directly. Other examples
      include the filamentation dynamics in CS2 liquid and the propagation dynamics in
      air related to the interaction with laser breakdown plasma. FTOP can also be used
      to extract information on the optical Kerr constant and its decay time in media.
      This method is useful in the monitoring of the intensity distribution in the
      nonlinear propagation of intense light pulses, which is a frequently studied
      subject in the field of physics regarding nonlinear optics and laser processing.

PMID- 12003228
TI  - Scattering matrix of infrared radiation by ice finite circular cylinders.
AB  - Scattering matrix characteristics of polydisperse, randomly oriented, small ice
      crystals modeled by finite circular cylinders with various ratios of the length
      to diameter (L/D) ratio are calculated by use of the exact T-matrix approach,
      with emphasis on the thermal infrared spectral region that extends from the
      atmospheric short-wave IR window to the far-IR wavelengths to as large as 30
      microm. The observed ice crystal size distribution and the well-known power-law
      distribution are considered. The results of the extensive calculations show that
      the characteristics of scattering matrix elements of small ice circular cylinders
      depend strongly on wavelengths and refractive indices, particle size
      distributions, and the L/D ratios. The applicability of the power-law
      distribution and particle shapes for light scattering calculations for small ice
      crystals is discussed. The effects of the effective variance of size distribution
      on light scattering characteristics are addressed. It seems from the behavior of
      scattering matrix elements of small ice crystals that the combination of 25 and
      3.979 microm has some advantages and potential applications for remote sensing of
      cirrus and other ice clouds.

PMID- 12003227
TI  - Feasibility of nonlinear Raman lidar based on stimulated Raman gain spectroscopy
      without a tunable laser.
AB  - A novel technique of lidar for atmospheric gas detection by use of stimulated
      Raman gain spectroscopy without any tunable laser is proposed. Detection
      sensitivity and detectable range are estimated on the basis of the lidar equation
      for CO2, CH4, and H2 in the atmosphere. The feasibility study clearly shows that
      the technique has a potential for application to lidar and that, in addition, the
      construction of the system is simpler than those of traditional differential
      absorption lidars.

PMID- 12003226
TI  - Optical trapping near resonance absorption.
AB  - Expressions for radiation-induced forces are presented for the case of a Rayleigh
      particle near the focus of a Gaussian laser beam at near-resonant conditions.
      Classical electromagnetic theory was used to obtain the dependence of the
      scattering and gradient forces on the incident laser frequency, the beam
      convergence angle, and the spatial position of the particle with respect to the
      focus. Approximative numerical analysis performed for particles with a single
      resonant absorption peak demonstrates the occurrence of up to 50-fold enhanced
      trapping forces at near-resonant frequencies. The use of this technique of
      gradient force enhancement may provide optical tweezers with enhanced trapping
      strengths and a degree of specificity.

PMID- 12003229
TI  - Isotope 18O/16O ratio measurements of water vapor by use of the 950-nm wavelength
      region with cavity ring-down and photoacoustic spectroscopic techniques.
AB  - Two optical methods, cavity ring-down spectroscopy and photoacoustic
      spectroscopy, are applied to the measurement of the isotope ratio 18O/16O in
      water-vapor samples with a Nd3+:YAG pumped-dye laser. The combination band of
      (2v1 + v3) in the 960-nm region of water molecules is investigated for two
      standard water samples, the Vienna Standard Mean Ocean Water and the Standard
      Light Antarctic Precipitation. The results demonstrate that the two methods have
      the potential of compact systems for in-situ measurements of H2O isotope ratio in
      the environment.

PMID- 12003230
TI  - Aging of reflective roofs: soot deposition.
AB  - Solar-reflective roofs remain cooler than absorptive roofs and thus conserve
      electricity otherwise needed for air conditioning. A currently controversial
      aspect of solar-reflective cool roofing is the extent to which an initially high
      solar reflectance decreases with time. We present experimental data on the
      spectral absorption of deposits that accumulate on roofs, and we attribute most
      of the absorption to carbon soot originally produced by combustion. The deposits
      absorb more at short wavelengths (e.g., in the blue) than in the red and
      infrared, imparting a slightly yellow tinge to formerly white surfaces. The
      initial rate of reflectance reduction by soot accumulation is consistent with
      known emission rates that are due to combustion. The long-term reflectance change
      appears to be determined by the ability of the soot to adhere to the roof,
      resisting washout by rain.

PMID- 12003231
TI  - Activation of microcomponents with light for micro-electro-mechanical systems and
      micro-optical-electro-mechanical systems applications.
AB  - We examine the light-activation properties of micrometer-sized gear structures
      fabricated with polysilicon surface micromachining techniques. The gears are held
      in place on a substrate through a capped anchor post and are free to rotate about
      the post. The light-activation technique is modeled on photon radiation pressure,
      and the equation of motion of the gear is solved for this activation technique.
      Experimental measurements of torque and damping are found to be consistent with
      expected results for micrometer-scale devices. Design optimization for optically
      actuated microstructures is discussed.

PMID- 12003232
TI  - Development of software in the study of carotid artery in the neck.
AB  - The aim of this work was to develop and employ software for the study of the
      common carotid artery and its branches in the neck. We first constructed
      geometric models of anatomic components, for the building of knowledge bases to
      be used in automatic feature extraction techniques from images. Then, we
      developed a software system characterised by three-dimensional visualisation,
      image processing functions, knowledge base and a programming language to describe
      classification processing by means of fuzzy logic. The software system was used
      to perform automatic reconstruction of three-dimensional models of carotid
      arteries from contiguous CT scans of the neck. These findings suggest that such
      software systems represent a useful help in the study of image based diagnosis of
      carotid arteries.

PMID- 12003233
TI  - Considerations on the ethics of corporeal donation and the handling of dead
      bodies.

PMID- 12003234
TI  - The blood supply of the papillary muscles of the left ventricle in the Hereford
      cattle.
AB  - The blood supply of the Papillary Muscle (PM) of the left ventricle, cranial (PM)
      and caudal (PM), in Hereford cattle was studied. The results obtained from the
      dissection of 50 hearts injected with neoprene latex, indicated that the cranial
      PM is supplied by collateral of the Ramus descendens paraconalis in all cases,
      alone or together with vessels from the Ramus circumflexus of the Arteria
      coronaria sinistra. The caudal PM is supplied from arteries coming mainly from
      the Ramus circumflexus of the A. coronaria sinistra, and also from the Ramus
      descendens subsinuosus and Ramus descendens paraconalis. When present, the A.
      diagonalis supplies the cranial PM and in some cases the caudal PM too. Thus this
      vessel can be termed "artery of the papillary muscle".

PMID- 12003235
TI  - Natural killer lymphocytes: "null cells" no more.
AB  - Natural Killer (NK) lymphocytes were initially described as potent effector cells
      that, unlike T lymphocytes, were able to kill targets in the absence of a priori
      stimulation and without specific recognition mechanisms. Over the past ten years
      however, it has been clearly demonstrated that NK cell function is regulated by a
      number of surface receptors that bind specific ligands expressed by target cells.
      Some of these receptors display inhibitory functions and recognize MHC class I
      molecules expressed by normal autologous cells that, as a consequence, are spared
      from indiscriminate NK-mediated killing. Other receptors are involved in NK cell
      activation against allogeneic cells or cells that, upon viral infection or tumor
      transformation, down-regulate MHC Class I expression. Altogether these data
      provide important advances toward the understanding of the complexity of the
      molecular mechanisms that regulate NK-mediated functions.

PMID- 12003236
TI  - Lipid membrane phase behaviour elucidated in real time by controlled environment
      atomic force microscopy.
AB  - Lipids are integral components of all biological membranes. Understanding the
      physical and chemical properties of these lipids is critical to our understanding
      of membrane functions. We developed a new atomic force microscope (AFM) approach
      to visualize in real time the temperature-induced lipid phase transition and
      domain separation processes in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)
      membranes and estimate the thermodynamics of the phase transition process. The
      gel and liquid crystalline phases of DMPC coexisted over a broad temperature
      range (approximately 10 degrees C). Equal partitioning into two phases occurred
      at a transition temperature (Tm) of 28.5 degrees C. We developed a mathematical
      model to analyse AFM-derived DMPC membrane height changes as multi-peak Gaussian
      distributions. This approach allowed us to estimate the DMPC domain size, N, as
      18-75 molecules per leaflet corresponding to a -4.2 nm diameter circular
      nanodomain. Lipid nanodomains may organize into microdomains or rafts which, in
      concert with proteins and other lipid components, play an important dynamic role
      in many biomedically important processes.

PMID- 12003237
TI  - A TEM study on melt-crystallized poly(butylene terephthalate).
AB  - A study was made to investigate an optimum condition for ruthenium tetraoxide
      staining of poly(butylene terephthalate) (PBT) with glass transition temperature
      as low as ca. 23 degrees C for TEM observation of melt-grown PBT crystals. The
      morphological study of ultrathin sections prepared based on optimum staining at
      25 degrees C for 8 h revealed formation of fringed-micellar crystal nuclei in the
      early stage and folded-chain fringed-micellar crystals in the later stage of
      isothermal crystallization at 40 degrees C from melt. The fraction of chain
      folded crystals increased with increasing crystallization temperature from the
      quantitative analysis of crystal thickness in comparison with the reported
      morphology using the replica method.

PMID- 12003238
TI  - Electron microscopy of pathogenic yeasts Cryptococcus neoformans and Exophiala
      dermatitidis by high-pressure freezing.
AB  - A high-pressure freezing method was used to observe the ultrastructure of
      pathogenic yeasts, Cryptococcus neoformans and Exophiala dermatitidis, after
      freeze-substitution and ultrathin sectioning. The method well preserved the cell
      structure in its natural state, since the capsule, cell wall, plasma membrane,
      nucleus, outer and inner nuclear membranes, nuclear pores, nucleolus,
      mitochondria, mitochondrial membrane and cristae, vacuoles, endoplasmic
      reticulum, Golgi apparatus, spindle pole body, ribosomes, lipid droplets,
      microtubules, actin filaments, and glycogen granules were clearly visible. The
      method was shown to freeze cells as deep as 0.1 mm by sectioning the sample
      perpendicular to specimen surface. The quality of the cell image was similar to
      that obtained by a rapid freezing method when compared using the same materials.
      Thus, high-pressure freezing would be useful for making serial ultrathin sections
      for three-dimensional analysis of cells, which should give basic information of
      structure and function of pathogenic yeast cells necessary for finding an
      effective therapy for mycoses.

PMID- 12003239
TI  - Energy-filtered electron diffraction and high-resolution electron microscopy on
      short-range ordered structure in GaAs(0.5)Sb(0.5).
AB  - Characteristic intensity distribution of diffuse scattering in III-V alloy
      semiconductor GaAs(0.5)Sb(0.5) epitaxially grown was observed by the energy
      filtered electron diffraction method with [110] incidence. The diffuse scattering
      situates at the one-third positions between the fundamental reflections extending
      parallel to the q002 direction in the reciprocal space. A high-resolution
      electron microscope image shows weak contrast modulation corresponding to the
      diffuse scattering. The image processed with the Fourier transform by selecting
      the diffuse scattering and a fundamental reflection shows small regions
      consisting of bright dots being elongated along the (111) planes and aligning on
      the (002) planes, which are considered to result from the ordering of As and Sb
      during the growth process. The effect of including the fundamental reflection for
      imaging the ordered regions in the image processing method is also discussed.
      Finally, based on the results obtained by energy-filtered electron diffraction
      and high-resolution electron microscopy, a simple structure model for the short
      range ordered structure in GaAs(0.5)Sb0.5 is proposed.

PMID- 12003240
TI  - Characteristic distribution of gap junctions in rat lacrimal gland in vivo and
      reconstruction of a gap junction in an in vitro model.
AB  - We investigated localization of the gap junction in rat lacrimal gland in vivo
      and in vitro using electron microscopy and immunostaining with anti-connexin32
      (Cx32) monoclonal antibody (HAM8). In immunofluorescence study of lacrimal gland
      tissues, Cx32 protein appeared to exist not only at the intercellular borders of
      acinar cells, but also in the basal regions, where there apparently was no
      contact with adjacent acinar cells. Thin sectioning and immunoelectron microscopy
      revealed that lacrimal acinar cells formed autocellular gap junctions (reflexive
      gap junctions) in the basal regions and intercellular gap junctions with adjacent
      acinar cell membranes. In immunofluorescence study of primary culture, Cx32
      protein was found on the free surfaces of isolated acinar cells at the early
      stage of culture. With culturing time, cell aggregates were formed. We observed
      Cx32 immunoreactivity between acinar cells in these aggregates, but not on their
      free surface. Electron microscopic study confirmed that these aggregates
      possessed intercellular gap junctions and morphologically differentiated acinar
      like structures. However, reflexive gap junctions were not observed in these
      aggregates. In conclusion, lacrimal acinar cells form intercellular and reflexive
      gap junctions in vivo. On the other hand, the existence of an acinar-like
      structure and intercellular gap junctions indicates that acinar cells
      differentiated in vitro morphologically. The cells may communicate with each
      other through these junctions, organizing themselves into an acinar cell network
      in an in vitro situation.

PMID- 12003241
TI  - Electrostatic correction of the chromatic and of the spherical aberration of
      charged-particle lenses (part II).
AB  - A doubly symmetric electrostatic corrector which compensates for the axial
      chromatic and the axial third-order aberration of charged-particle lenses is
      outlined. Due to the double symmetry the corrector does not introduce linear off
      axis aberrations and yields in combination with a round objective lens an
      electron-optical aplanat. The principle of the electrostatic correction of the
      axial chromatic aberration is explained in mathematical terms. The geometry of
      the electrodes of a suitable corrector is optimized with respect to the chromatic
      correction, the maximum strength of the electric field, and the residual higher
      order aberrations which limit the resolution. The resulting aplanat achieves a
      resolution limit of about 2 nm for an image field with a diameter of 1500 nm. The
      required stabilities of the electric power supplies are discussed in detail.

PMID- 12003242
TI  - Low voltage FE-STEM for characterization of state-of-the-art silicon SRAM.
AB  - Low voltage (30 kV) field emission scanning transmission electron microscopy (FE
      STEM) has been employed in the characterization of state-of-the-art semiconductor
      static random access memory (SRAM) using specimens prepared at several different
      thicknesses (70-180 nm). A focused ion beam (FIB) system, a FIB-SEM compatible
      specimen holder and an in-lens FE-SEM have been employed for alternating between
      FIB milling and SEM/ STEM imaging. As a result, ion implanted atom damage during
      manufacturing, grains in aluminium interconnects, poly silicon gates, thin metal
      barriers and a thin gate oxide layer were observed by low voltage FE-STEM. STEM,
      in-lens FESEM, FIB

PMID- 12003243
TI  - A SAED and HREM study of structural defects in brownmillerite, LaBa(x)Sr(1
      x)CuGaOy related oxides.
AB  - The synthesis and microstructural characterization, by means of selected area
      electron diffraction (SAED) and high resolution electron microscopy (HREM), of
      the solid solution LaBa(x)Sr(1-x)CuGaO5 (0.1 < or = 5 x < or = 0.9) is reported.
      Although an average brownmillerite Ima2 structure is proposed for the whole
      compositional range, SAED and HREM clearly show that structural defects appear as
      barium content increases.

PMID- 12003244
TI  - Simulations of Kikuchi patterns due to thermal diffuse scattering on MgO
      crystals.
AB  - Inelastic scattering of fast transmission electrons from a perfect crystal is
      investigated using the Bloch wave theory. A comprehensive expression for the
      scattering of electrons is given, which includes both elastic and inelastic
      multiple scatterings. This expression is an extended form of Fujimoto's
      expression for elastic scattering (J. Phys. Soc. Japan 14:1558 (1959)). For the
      approximation of single inelastic scattering, the expression becomes equivalent
      to the formula of Rez et al. (Phil. Mag. 35: 81 (1977)). When thermal diffuse
      scattering (TDS) is considered using the Einstein model or the scattering factor
      for TDS given by Hall and Hirsch (Proc. R. Soc. A 286: 158 (1965)), Rossouw and
      Bursill's expression (Acta Cryst. A 41: 320 (1985)) is derived. This expression
      has been used in computer simulations of TDS intensity distribution (Kikuchi
      pattern). It is shown that the simulations for magnesium oxide (MgO) using 357
      beams agree quite well with the experimental ones.

PMID- 12003245
TI  - Sub-micromorphology of the epicuticle of hornets: AFM studies.
AB  - The upper part of the hornet cuticle in the abdominal region reveals several
      structures. First, situated at intervals of 10 microm or more apart, there are
      depressions housing a peripheral photoreceptor (PP) and between every two of
      these, there are horizontal flats resembling an irregular polygon which are
      mostly elongated and about 100 microm2 in area. Upon each such terrace-like flat
      there are tile-shaped protuberances up to several micrometres in length and
      mostly running parallel to one another, covering the entire surface. Between
      every two such terraces there is a 'step' of up to 1.4 microm in height. Both the
      'tiles' and 'steps' terminate in front of the distal part of each PP, which is a
      recessed and smooth region. Secondly, in other regions of the cuticle one can
      note other surface configurations such as: (a) a paucity of 'tiles'; (b) no
      'tiles' at all but a chessboard-like pattern, the 'squares' of which contain
      rectangles recessed to various depths, interspersed among 'plaques' that are not
      recessed and may even protrude; and (c) anfractuous (characterized by windings
      and turnings) flats that are intermittently criss-crossed by grooves. In addition
      to the above, most of the cuticle also displays numerous setae (i.e. small
      hairs). We suppose that all the described structures and configurations either
      contribute to enlargement of the cuticular surface, or act as an optical grid,
      thereby enhancing the absorption of light. We further speculate that for hornets
      in flight, situations may arise where part of the above mentioned structures
      orientates perpendicular to the sunlight and this entire orientation acts to
      direct the solar energy toward and into the PP so as to enable greater
      utilization of light as an energy source.

PMID- 12003246
TI  - Dementia in developing countries.

PMID- 12003247
TI  - The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic
      and aggressive behavior in Alzheimer disease.
AB  - BACKGROUND: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis,
      AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive
      and functional decline and a liability to aggressive behaviors. We recently found
      that AD subjects homozygous for long alleles (l) of an insertion/deletion
      polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had
      elevated rates of aggressive behavior. OBJECTIVE: To examine whether the 5-HTTPR
      ll genotype confers an increased risk of AD+P, and of the combined
      AD+P/aggressive phenotype. METHODS: The 5-HTTPR genotype was determined in 332
      subjects diagnosed with possible or probable AD. All subjects received structured
      psychiatric assessments and were categorized with regard to their history of
      aggressive behaviors and psychotic symptoms. RESULTS: Consistent with other
      reports, AD+P was associated with a significant increased risk for aggressive
      behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll
      genotype and with an increased l allele frequency. Subjects with the combined
      behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll
      genotype and highest l allele frequency. CONCLUSION: The 5-HTTPR l allele appears
      to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this
      association in a similar behaviorally well-characterized independent sample is
      needed.

PMID- 12003248
TI  - Diagnosis of preclinical Alzheimer's disease in a clinical setting.
AB  - INTRODUCTION: The aim of the study was to investigate whether the preclinical
      stage of Alzheimer's disease (AD) can be diagnosed in a clinical setting. To this
      end we investigated whether subjects with preclinical AD could be differentiated
      from subjects with nonprogressive mild cognitive impairment and from subjects
      with very mild AD-type dementia. METHODS: Twenty-three subjects with preclinical
      AD, 44 subjects with nonprogressive mild cognitive impairment, and 25 subjects
      with very mild AD-type dementia were selected from a memory clinic population.
      Variables that were used to differentiate the groups were demographic variables,
      the Mini-Mental State Examination score, performance on cognitive tests, measures
      of functional impairment, and measures of noncognitive symptomatology. RESULTS:
      Age and the scores for the delayed recall task could best discriminate between
      subjects with preclinical AD and subjects with nonprogressive mild cognitive
      impairment. The overall accuracy was 87%. The score on the Global Deterioration
      Scale and a measure of intelligence could best discriminate between subjects with
      preclinical AD and subjects with very mild AD-type dementia. The overall accuracy
      was 85%. CONCLUSIONS: Subjects with preclinical AD can be distinguished from
      subjects with nonprogressive mild cognitive impairment and from subjects with
      very mild AD-type dementia. This means that preclinical AD is a diagnostic entity
      for which clinical criteria should be developed.

PMID- 12003249
TI  - Healthy aging among inner-city men.
AB  - OBJECTIVE: Until now, prospective studies of aging have begun with 50- to 60-year
      olds, not adolescents. Premature deaths, childhood variables, and alcohol abuse
      have been often ignored. So has positive aging. As people live longer,
      gerontology needs to understand the determinants of health as well as illness in
      the later years. METHOD: The present study follows a cohort of adolescent boys
      (332 inner-city youths) for 60 years or until death. Complete physical exams were
      obtained every 5 years and psychosocial data every 2 years. Predictor variables
      assessed prior to age 50 include six variables reflecting uncontrollable factors-
      parental social class, environmental strengths, number of family problems, major
      depression, ancestral longevity, and premorbid physical health at age 50--and six
      variables reflecting (at least some) personal control: alcohol abuse, smoking,
      marital stability, body mass index, coping mechanisms, and education. The four
      outcome variables chosen to assess healthy aging at 70 reflected both "mind" and
      "body." They included objectively assessed variables (death and/or disability
      prior to 70, and objective mental health) and two subjectively assessed variables
      (perceived instrumental activities of daily living and life enjoyment). RESULTS:
      Multivariate analysis suggested that positive aging at 70 could be predicted by
      variables assessed prior to age 50. More hopeful still, if the six variables
      under some personal control were controlled, depression was the only
      uncontrollable variable that affected the quality of subjective and objective
      aging. CONCLUSIONS: First, we may have greater personal control over our
      biopsychosocial health after retirement than previously recognized. Second, in
      this cohort, psychiatric rather than sociological predictors appeared more
      important.

PMID- 12003250
TI  - Prevalence of dementia in an urban Indian population.
AB  - This article reports the findings of a 3-year epidemiological survey for dementia
      in an urban community-resident population in Mumbai (Bombay), India, wherein the
      prevalence of all types of dementia was determined. METHOD: The study was
      conducted in three stages. Stage 1: From a potential pool of 30,000 subjects aged
      40 years or more, 24,488 (male = 11,875; female = 12,613) persons completed self
      report or interviewer-rated protocols based on the Sandoz Clinical Assessment
      Geriatric Scale, but 5,512 (18.37%) persons refused to participate. Scores on the
      protocol had a possible range from 0 through 34. Stage 2: Persons with a score +2
      SD above the mean were selected in this stage where the persons were screened for
      cognitive functioning using a modified and translated version of the Mini-Mental
      State Examination. Individuals who scored below the 5th percentile were included
      in Stage 3 and underwent a detailed neurological, psychiatric, and
      neuropsychological evaluation as well as hematological, radiological,
      electrocardiographic, and electroencephalographic investigations. Diagnoses were
      made jointly by a neurologist, psychiatrist, and psychologist using the DSM-IV
      diagnostic criteria. Subjects were also rated on the Clinical Dementia Rating
      (CDR) scale and assessed for activities of daily living. RESULTS: One hundred
      five subjects with dementia (CDR > or = 0.5) were identified in this population
      of 24,488 persons. The prevalence rate for dementia in those aged 40 years and
      more was 0.43% and for persons aged 65 and above was 2.44%. Seventy-eight
      individuals had a CDR of > or = 1 yielding an overall prevalence rate of 0.32%,
      and a prevalence rate of 1.81% for those aged 65 years and older. The overall
      prevalence rate for Alzheimer's disease (AD) in the population was 0.25%, and
      1.5% for those aged 65 years and above. AD (n = 62; 65%) was the most common
      cause of dementia followed byvascular dementia (n = 23; 22%). There were more
      women (n = 38) than men (n = 24) in the AD group. Increasing age was associated
      with a higher prevalence of the dementia syndrome in general as well as AD
      specifically. CONCLUSION: In the population surveyed, the prevalence of AD and
      other dementias is less than that reported from developed countries but similar
      to results of other studies in India. Prevalence of the dementia syndrome
      increased with age and was not related to gender. AD was the most common dementia
      and the prevalence was higher in women than in men. Results are discussed with
      respect to shorter life expectancy, relocation of affected persons, and
      differences in the risk factors as compared to developed countries.

PMID- 12003251
TI  - Does apolipoprotein E influence learning and memory in the nondemented oldest
      old?
AB  - The objective of this study was to analyze the relationship of the apolipoprotein
      E (apoE) epsilon4 and epsilon2 alleles to learning and memory performances in the
      nondemented oldest old. Forty-six nondemented persons aged 85 years or over from
      a randomly selected group of 128 subjects in Vantaa, Finland, were studied. ApoE
      genotyping was performed using the minisequencing technique. A structured
      clinical examination and interview were carried out. The test variables studied
      were learning and memory scores (from the Fuld Object-Memory Evaluation), verbal
      fluency, and conceptualization (the Similarities subtest of the WAIS-R). We
      compared apoE-epsilon4 carriers to noncarriers and apoE-epsilon2 carriers to
      noncarriers. No statistically significant differences were found in any of the
      test variables. The results failed to confirm the hypotheses that poor cognitive
      performance is associated with the apoE-epsilon4 allele and good performance with
      the apoE-epsilon2 allele in the oldest old. This suggests that the apoE alleles
      do not have a detectable relationship to learning and memory in nondemented very
      elderly people.

PMID- 12003252
TI  - Butyrylcholinesterase and cognitive function.
AB  - Butyrylcholinesterase (BuChE) is expressed in brain structures involved in
      cognition, but the effect of selective BuChE inhibitors on human cognitive
      function is unknown. We report a patient whose cognitive function deteriorated
      following a reduction and improved following reinstitution of ethopropazine, a
      selective BuChE inhibitor. We suggest that, because neurons expressing BuChE may
      be involved in cognition, there is merit to further evaluation of selective BuChE
      inhibitors in treating cognitive dysfunction.

PMID- 12003253
TI  - Effects of transdermal nicotine on learning, memory, verbal fluency,
      concentration, and general health in a healthy sample at risk for dementia.
AB  - Nicotinic receptor loss has been implicated in the pathogenesis of Alzheimer's
      disease. The present study investigated the effects of chronic low-dose
      transdermal nicotine in a cohort of nondemented, healthy volunteers (mean age 63
      years). The majority of subjects (85%) had a first-degree relation with dementia.
      Subjects were tested using a before, during, and after design on a battery of
      tests known to be sensitive to early cognitive decline. A mixed pattern of
      results was seen, with significant changes occurring with verbal learning, object
      learning, delayed recall, and word retrieval. Nicotine had no effect on measures
      of concentration or psychomotor speed. The effects were most noticeable in
      subjects at the lower end of baseline test performance on the tasks used. The
      results are discussed with reference to the relationship between strategic
      nicotinic receptor loss and measurable psychometric change. The potential
      therapeutic role of nicotinic agonists in preclinical "at risk" individuals is
      supported by the results of this study.

PMID- 12003254
TI  - How to help depressed older people living in residential care: a multifaceted
      shared-care intervention for late-life depression.
AB  - OBJECTIVE: To describe a population-based, multifaceted shared-care intervention
      for late-life depression in residential care as a new model of geriatric
      practice, to outline its development and implementation, and to describe the
      lessons learned during the implementation process. SETTING: A large continuing
      care retirement community in Sydney, Australia, providing three levels of care
      (independent living units, assisted-living complexes, and nursing homes).
      PARTICIPANTS: The intervention was implemented for the entire non-nursing home
      population (residents in independent and assisted living: N = 1,466) of the
      facility and their health care providers. Of the 1,036 residents whowere eligible
      and agreed to be interviewed, 281 (27.1%) were classified as depressed according
      to the Geriatric Depression Scale. INTERVENTION DESCRIPTION: The intervention
      included: (a) multidisciplinary collaboration between primary care physicians,
      facility health care providers, and the local psychogeriatric service; (b)
      training for primary care physicians and other facility health care providers
      about detecting and managing depression; and (c) depression-related health
      education/promotion programs for residents. CONCLUSIONS: The intervention was
      widely accepted by residents and their health care providers, and was sustained
      and enhanced by the facility after the completion of the study. It is possible to
      implement and sustain a multifaceted shared-care intervention for late-life
      depression in a residential care facility where local psychogeriatric services
      are scarce, staff-to-resident ratios are low, and the needs of depressed
      residents are substantial.

PMID- 12003255
TI  - Effects of left ventricular systolic dysfunction on left atrial appendage and
      left atrial functions in patients with chronic nonvalvular atrial fibrillation.
AB  - OBJECTIVE: It has been claimed that left ventricular (LV) systolic dysfunction
      impairs left atrial (LA) and left atrial appendage (LAA) functions. In this
      study, we compared the LA and LAA function parameters in patients with chronic
      nonvalvular atrial fibrillation (AF) with and without LV systolic dysfunction.
      METHODS AND RESULTS: The study population consisted of 28 patients with chronic
      nonvalvularAF. Group I consisted of 12 patients with LV systolic dysfunction
      (mean age: 61 +/- 14 years; LV ejection fraction: 44 +/- 6%), group II of 16
      patients with normal LV systolic function (mean age: 52 +/- 15 years; LV ejection
      fraction: 65 +/- 3%). LV ejection fraction (EF) was measured by echocardiography
      utilizing bi-plane area length method. The following LA and LAA transoesophageal
      echocardiography parameters were obtained: I) LA diameter, 2) LAA ejection
      velocity, 3) LAA filling velocity, 4) LAA ejection fraction, 5) pulmonary venous
      (PV) systolic velocity, 6) PV diastolic velocity, 7) PV systolic
      velocity/diastolic velocity ratio. The left atrium diameter was significantly
      larger in group I than in group 11 (4.7 +/- 0.7 cm vs. 3.8 +/- 0.6 cm, p < 0.05).
      The LAA ejection velocity and LAA ejection fraction were significantly lower in
      group I than in group 11 (22.6 +/- 15.5 cm/s vs 37.5 +/- 11.3 cm/s and 26.9 +/-
      20.8% vs. 41.3 +/- 10.9%, p < 0.05 for both comparisons). The PV systolic
      velocity and PV systolic velocity/diastolic velocity ratio were significantly
      smaller in group I than in group II (26.2 +/- 14.8 cm/s vs. 51.5 +/- 22 cm/s and
      0.7 +/- 0.6 vs. 1.2 +/- 0.5, p < 0.05 for both comparisons). Although decreased
      LAA filling and PV diastolic velocities were determined in group I, no
      significant difference existed between groups I and II. Thrombus and/or
      spontaneous echo contrast (SEC) in the LA and/or LAA were more frequent in group
      I (75% vs. 18%, p < 0.05). CONCLUSION: These results indicate that LV systolic
      dysfunction impairs various LA and LA function parameters and is associated with
      an increased frequency of SEC and/or LA thrombus in patients with chronic
      nonvalvularAF.

PMID- 12003256
TI  - Cannulation of a LIMA graft via the right brachial arterial route using a MANI
      catheter: an alternative approach.
AB  - Some different revascularization methods including coronary artery bypass surgery
      can be performed in the treatment of coronary artery disease. Saphenous vein
      grafts and/or arterial grafts including left internal mammary artery (LIMA) can
      be implanted during coronary bypass surgery. It is necessary to perform
      cannulation of the LIMA, in order to diagnose and treat these patients. In
      addition to conventional internal mammary artery catheters, several types of
      catheters can be used for this purpose. In general, LIMA catheterization via the
      femoral artery has been preferred over other methods. However, the right brachial
      arterial approach can be mandatory in some rare conditions. In this report, we
      describe an alternative method to the conventional techniques of the LIMA graft
      angiography via the right brachial arterial approach using a MANI catheter.
      According to our knowledge, no data are available using the MANI catheter for
      this purpose in the current literature.

PMID- 12003257
TI  - Effects of a plant sterol-enriched spread on serum lipids and lipoproteins in
      mildly hypercholesterolaemic subjects.
AB  - OBJECTIVE: In this randomized double-blind placebo-controlled cross-over study
      the effects of spreads enriched with plant sterols were determined on serum
      lipids, lipoprotein and apolipoprotein concentrations in a Belgian population.
      METHODS: Fourty-two healthy adult volunteers (22 men and 20 women) with an
      average age of 55 (SD 9) years and with serum total cholesterol concentrations
      below 300 mg/dl, consumed during two consecutive periods of 4 weeks two different
      low-fat spreads. Both the plant sterol rich and control spreads contained 35% of
      fat and had an almost equal fat composition. The sterol content of the enriched
      spread was 8.3%. Intake of the spreads was 25 g/day. RESULTS: Serum total and LDL
      cholesterol concentrations lowered by 7% (18 mg/dl) and 10% (16 mg/dl),
      respectively, with the plant sterol-enriched compared to the control spread.
      Serum HDL-cholesterol concentration did not significantly differ between the two
      spreads. Apolipoprotein B concentrations lowered by 8% (0.08 g/l) with the plant
      sterol-enriched spread, while concentrations of apolipoprotein A-I did not
      change. CONCLUSION: These findings indicate that a daily intake of 25 gram low
      fat spread containing 2 gram plant sterol per day is effective in lowering blood
      total and LDL cholesterol, and apolipoprotein B concentrations. This lowering may
      help to reduce the risk of heart disease in the population.

PMID- 12003258
TI  - Awareness, treatment and control of hyperlipidaemia in middle-aged men in France
      and northern ireland in 1991-1993: the PRIME study. Prospective epidemiological
      study of myocardial infarction.
AB  - OBJECTIVE: To assess how well screening and preventive measures are implemented
      in the general population. METHODS AND RESULTS: Sample of 9,609 men aged 50-59
      devoid of history of CHD living in France and Northern Ireland. Hyperlipidaemia
      was defined as total cholesterol > or = 240 mg/dl or triglycerides > or = 200
      mg/dl or HDL cholesterol < 0.35 mg/dl or hypolipidaemic drug treatment. Treated
      subjects were considered as controlled if total cholesterol was < 200 mg/dland
      triglycerides < 200 mg/dl and HDL cholesterol > or = 0.35 mg/dl. The prevalence
      of hyperlipidaemia was higher in Northern Ireland, whereas awareness, treatment
      and control rates were higher in France. Only one third of aware subjects had a
      hypolipidaemic diet, and less than half of treated subjects was adequately
      controlled. Lower educational level, smoking, obesity and a history of
      hypertension were significantly related to higher rates of hyperlipidaemia in
      both countries. In France, history of hypertension or diabetes, and ex- or non
      smoking status were related to higher levels of awareness and treatment. In
      Northern Ireland, awareness of hyperlipidaemia was positively related to
      educational level. CONCLUSIONS: Awareness, treatment and control rates for
      hyperlipidaemia are low in Northern Ireland compared to France, and
      implementation of preventive measures should be performed in both countries.

PMID- 12003259
TI  - Accidental detection of a giant right atrial aneurysm in an asymptomatic infant.
AB  - We present a 4-month old infant boy accidentally detected to have cardiomegaly on
      a chest radiograph, and on further investigation discovered to have a giant right
      atrial aneurysm and a secundum atrial septal defect. Congenital right atrial
      aneurysm or diverticulum is a rare anomaly, usually presenting with atrial or
      supraventricular tachycardia. Previously reported patients did not have any
      associated congenital heart defect. Although asymptomatic our patient needs close
      follow-up, and surgical resettion of the aneurysm and closure of the atrial
      septal defect in view of potential complications.

PMID- 12003260
TI  - Changing frequency of cardiovascular diseases and cancer with age: the USA, 1999.

PMID- 12003261
TI  - Physical exercise and coronary artery disease.

PMID- 12003262
TI  - Syndecan-1 expression in laryngeal cancer.
AB  - Syndecan-1 is a member of the syndecan family of cell surface heparan sulphate
      proteoglycans. The aim of this study was the evaluation of syndecan-1 expression
      in laryngeal cancer. The findings were correlated both with the clinico
      pathological parameters of the tumours and with patient survival. Paraffin
      embedded samples from 48 patients with laryngeal cancer selected from the files
      of the ENT Department of the Medical Academy in Lublin were immunostained with
      anti-syndecan-1 monoclonal antibody. The patients' mean age was 56 years, and 69%
      survived for over 3 years. Syndecan-1 immunoreactivity was observed in 48 (100%)
      of carcinomas. In our study, statistically significant correlations were observed
      both between syndecan-1 expression and patient survival (Chi-square = 4.364;
      P<0.05) and between syndecan-1 expression and clinical stage of disease (Chi
      square = 4.363; P<0.05). Significant differences in syndecan-1 expression were
      also observed with various stages of histological differentiation of the
      carcinomas (Chi-square = 6.588; P<0.05), and also according to the presence or
      absence of metastatic changes in the regional lymph nodes (Chi-square = 6.289;
      P<0.05). Our results indicate that syndecan-1 could be used as a prognostic
      marker in laryngeal cancer.

PMID- 12003263
TI  - Neuromuscular hamartoma of the cochlear nerve: a rare occurrence in the internal
      auditory meatus.
AB  - The authors present a case of neuromuscular hamartoma of the cochlear nerve, an
      unusual occurrence in the internal auditory meatus (IAM). A review of the
      literature shows no previous report of neuromuscular hamartoma of the cochlear
      nerve. This tumour was clinically and radiologically difficult to distinguish
      from acoustic neuroma. It is important to consider the diagnosis of these rare
      small tumours pre-operatively, as it may be appropriate to manage this
      conservatively.

PMID- 12003264
TI  - Avian dark cells.
AB  - Dark cells (DCs) of mammalian and non-mammalian species help to maintain the
      homeostasis of the inner ear fluids in vivo. Although the avian cochlea is
      straight and the mammalian cochlea is coiled, no significant difference in the
      morphology and/or function of mammalian and avian DCs has been reported. The
      mammalian equivalent of avian DCs are marginal cells and are located in the stria
      vascularis along a bony sheet. Avian DCs hang free from the tegmentum vasculosum
      (TV) of the avian lagena between the perilymph and endolymph. Frame averaging was
      used to image the fluorescence emitted by several fluorochromes applied to
      freshly isolated dark cells (iDCs) from chickens (Gallus domesticus) inner ears.
      The viability of iDCs was monitored via trypan blue exclusion at each isolation
      step. Sodium Green, BCECF-AM, Rhodamine 123 and 9-anthroyl ouabain molecules were
      used to test iDC function. These fluorochromes label iDCs ionic transmembrane
      trafficking function, membrane electrogenic potentials and Na+/K+ ATPase pump's
      activity. Na+/K+ ATPase pump sites, were also evaluated by the p-nitrophenyl
      phosphatase reaction. These results suggest that iDCs remain viable for several
      hours after isolation without special culturing requirements and that the number
      and functional activity of Na+/K+ ATPase pumps in the iDCs were indistinguishable
      from in vivo DCs. Primary cultures of freshly iDCs were successfully maintained
      for 28 days in plastic dishes with RPMI 1640 culture medium. The preparation of
      iDCs overcomes the difficulty of DCs accessability in vivo and the unavoidable
      contamination that rupturing the inner ear microenvironments induces.

PMID- 12003265
TI  - First report of parotid gland metastasis in multiple enchondromatosis with
      secondary CHOSA (G-III).
AB  - Chondrosarcomas constitute the second-most-frequent malignant bone tumors,
      representing about 10% of all malignant bone tumors. The most frequent
      localizations comprise the trunk, pelvis and limbs. Metastatic disease usually
      occurs in the lung; metastases to other localizations are seen occasionally.
      Manifestation in the head and neck area, either as primary tumor or metastasis,
      is very rare. A case of parotid gland metastasis in multiple enchondromatosis
      secondary chondrosarcoma (CHOSA) G-III of the left femoral bone is presented. A
      79-year-old male patient reported to our clinic with a rapidly progressing mass
      in the left parotid gland. A superficial parotidectomy was performed and the
      entire tumor resected. Histopathological examination revealed nodular
      infiltration of the parotid by chondrosarcoma consistent with metastatic disease.
      Review of the literature shows that this is the first report of such a case.

PMID- 12003266
TI  - Malignant epithelial salivary gland tumors in northern Finland: incidence and
      clinical characteristics.
AB  - A population-based survey was conducted in Northern Finland to evaluate the
      incidence rate as well as the patient and tumor characteristics of malignant
      epithelial salivary gland tumors diagnosed between 1988 and 1998. A total of 40
      new cases of malignant epithelial salivary gland tumors were diagnosed and
      separately evaluated. The age-standardized incidence rates (per 100,000 years)
      were 0.51 among men and 0.35 among women, giving an overall incidence rate of
      0.43. About half of the patients suffered from pain, which was the most common
      symptom along with palpable resistance, but the duration of symptoms varied
      widely (median: 11 months). Of all the malignant epithelial salivary gland tumors
      analyzed in our study, fine-needle aspiration cytology correctly indicated
      malignancy in only 28% of the cases.

PMID- 12003267
TI  - Genotoxicity studies on permethrin, DEET and diazinon in primary human nasal
      mucosal cells.
AB  - Possible genotoxic effects exerted by three widely used pesticides, permethrin,
      N,N-diethyl-m-toluamide (DEET) and diazinon, in primary human nasal mucosal cells
      were investigated. Primary nasal mucosa cells were prepared from tissue biopsies
      taken from 21 patients who underwent nasal surgery. Cells were exposed to 0.5-1.0
      mM concentrations of permethrin, DEET and diazinon for 60 min. Genotoxic effects
      were detected by the alkaline microgel electrophoresis assay ("comet assay").
      Within the concentration range, no significant cytotoxic effects were observed,
      but all three tested pesticides showed a significant genotoxic response that was
      concentration dependent. More pronounced genotoxic effects were observed in
      mucosal cells from the middle turbinate than in the inferior turbinate. The
      results provide some evidence for the potential carcinogenicity of these agents
      to human nasal mucosal cells. This should be further investigated.

PMID- 12003268
TI  - Diagnostic work-up of socially unacceptable snoring. I. History or sleep
      registration.
AB  - Should all patients with socially unacceptable snoring (SUS) undergo
      polysomnography, or is history-taking sufficient to identify the presence of
      obstructive sleep apnoea syndrome (OSAS)? Three hundred and eighty consecutive
      patients with SUS who underwent sleep registration were evaluated retrospectively
      to determine the predictive value of a history of apnoea or excessive daytime
      somnolence (hypersomnia). Of the patients analysed, 54% had OSAS, defined as an
      apnoea/hypopnoea index (AHI) of >15. This is higher than previously reported in
      the literature (46.7%). (Incidental) apnoea was reported by 337 (89%) of the
      patients, with a sensitivity of 0.92 and a specificity of 0.13. The predictive
      value--as related to the gold standard, i.e. sleep registration, of a negative
      test and of a positive test for OSAS is low (0.56 and 0.59, respectively).
      Hypersomnia was reported by 280 (74%) of the patients, with a sensitivity of 0.29
      and a specificity of 0.72. The predictive value of a negative test and a positive
      test for OSAS is also low, 0.45 and 0.56, respectively. These data confirm that
      apnoea and hypersomnia in the history do not have a reliable predictive value of
      an obstructive sleep apnoea syndrome. We conclude that sleep registration is
      indicated in all patients with SUS, to rule out or confirm the presence of OSAS.

PMID- 12003269
TI  - Diagnostic work-up of socially unacceptable snoring. II. Sleep endoscopy.
AB  - In the diagnostic work-up of socially unacceptable snoring (SUS) with or without
      a history suggestive of obstructive sleep apnoea syndrome (OSAS), information on
      the severity of the pathology as well as on local and general causative factors
      is needed. In part I of this study, we reported on the findings recorded in 380
      patients by means of sleep registration. In this part, our emphasis is on
      analysis of the local contributing factors. In 340 of the 380 patients sleep
      endoscopy was performed to establish the level(s) of obstruction as accurately as
      possible. Sleep endoscopy was performed following artificial induction of sleep
      with midazolam and consisted in endoscopy and flexible nasopharyngoscopy and
      laryngoscopy. Although obstruction at the oropharyngeal level was often present,
      obstructions at lower levels or at multiple levels were also frequently found. In
      many cases sleep endoscopy showed obstruction at different level(s) than had been
      suspected on the grounds of ear nose and throat (ENT) investigation only. An
      obstruction at only one level was recorded in 35% of the patients (119), while
      65% of patients (221) had multiple-level obstruction. The level(s) of obstruction
      could be well established by sleep endoscopy. We conclude that a diagnostic work
      up involving a combination of sleep registration, sleep endoscopy, and analysis
      of general factors is worthwhile. Combining the results of these tests makes it
      possible to give individually tailored advice on treatment.

PMID- 12003270
TI  - Haemorrhagic venous infarction following the posterior petrosal approach for
      acoustic neurinoma surgery: a report of two cases.
AB  - The authors report two surgical cases with acoustic neurinoma in which
      haemorrhagic infarction occurred via a compromise in cerebral deep venous
      outflow. In both cases, surgery was performed via the posterior petrosal
      approach, and the neurinomas were completely removed. In the first case, the
      haemorrhagic infarction was considered to have resulted from transection of the
      tentorial sinus, the presence of which had not been predictable by preoperative
      angiography. In the second case, the haemorrhagic infarction was caused by a
      coagulation of the petrosal vein, which was firmly adherent to a tumour. With the
      posterior petrosal approach, meticulous care is necessary to preserve the deep
      anastomotic veins into and around the cerebellar tentorium. Thereby, catastrophic
      morbidity related to compromised deep cerebral venous outflow can be avoided.

PMID- 12003271
TI  - The effect of basic fibroblast growth factor on the regeneration of guinea pig
      olfactory epithelium.
AB  - Olfactory receptor cells are widely thought to regenerate after degeneration and
      also thought to show turnover in normal circumstances in animal olfactory
      epithelium. The identity of the factor that controls proliferation and
      differentiation of olfactory receptor cells is a very important problem that has
      yet to be resolved. In this study, the mitogenic effects of epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF) on olfactory receptor
      cells in guinea pig olfactory epithelium was examined. The intraperitoneal
      injection of 1,000 ng bFGF/day for 14 days increased the cells in proliferation
      detected by immunostaining with proliferating cell nuclear antigen (PCNA), while
      neither EGF nor low-dose bFGF had any effect. These results support the idea that
      an adequate dose of bFGF plays an important role in the neurogenesis in the
      olfactory epithelium. Further study is needed to clarify the efficacy of bFGF in
      the damaged olfactory epithelium, but bFGF may provide a therapeutic option for
      olfactory disturbances caused by complete or partial loss of olfactory receptor
      cells.

PMID- 12003272
TI  - Remarkable restoration of speech discrimination after removal of jugular foramen
      schwannoma: a case report.

PMID- 12003273
TI  - Sport performance: variable or construct?

PMID- 12003274
TI  - Biomechanical differences in soccer kicking with the preferred and the non
      preferred leg.
AB  - The aims of this study were to examine the release speed of the ball in maximal
      instep kicking with the preferred and the non-preferred leg and to relate ball
      speed to biomechanical differences observed during the kicking action. Seven
      skilled soccer players performed maximal speed place kicks with the preferred and
      the non-preferred leg; their movements were filmed at 400 Hz. The inter-segmental
      kinematics and kinetics were derived. A coefficient of restitution between the
      foot and the ball was calculated and rate of force development in the hip flexors
      and the knee extensors was measured using a Kin-Com dynamometer. Higher ball
      speeds were achieved with the preferred leg as a result of the higher foot speed
      and coefficient of restitution at the time of impact compared with the non
      preferred leg. These higher foot speeds were caused by a greater amount of work
      on the shank originating from the angular velocity of the thigh. No differences
      were found in muscle moments or rate of force development. We conclude that the
      difference in maximal ball speed between the preferred and the non-preferred leg
      is caused by a better inter-segmental motion pattern and a transfer of velocity
      from the foot to the ball when kicking with the preferred leg.

PMID- 12003275
TI  - Sequential muscle activity and its functional role in the upper extremity and
      trunk during overarm throwing.
AB  - The proximal-to-distal segmental sequence has been identified in many sports
      activities, including baseball pitching and ball kicking. However, proximal-to
      distal sequential muscle activity has not been identified. The aims of this study
      were to establish whether sequential muscle activity does occur and, if it does,
      to determine its functional role. We recorded surface electromyograms (EMGs) for
      17 muscles from the upper extremity and abdomen during overarm throwing and
      detected the onset and peak times as indices of muscle activity. The following
      electromyographic properties were commonly identified in the participants. First,
      sequential muscle activity was observed from the scapular protractors to the
      shoulder horizontal flexors and from the shoulder horizontal flexors to the elbow
      extensor, but not from the elbow extensor to the wrist flexor or forearm
      pronator. Secondly, the external oblique contralateral to the throwing arm became
      activated before the ipsilateral external oblique. This sequence is considered to
      be very effective for the generation of high force and energy in the trunk.
      Thirdly, the ipsilateral external oblique began its activity almost at foot
      strike. Finally, the main activity of the rectus abdominis appeared just before
      the point of release.

PMID- 12003276
TI  - Fatigue decreases skilled tennis performance.
AB  - The aim of this study was to examine the effect of fatigue from maximal tennis
      hitting on skilled tennis performance. Eighteen senior county tennis players (9
      males, 9 females) volunteered to participate in the study. Their mean (+/-
      s(mean)) age and body mass were as follows: males 20.7 +/- 0.9 years and 60.6 +/-
      2.7 kg respectively, females 21.7 +/- 0.6 years and 71.5 +/- 1.8 kg respectively.
      The players undertook two performance tests, both against a tennis ball serving
      machine, on an indoor tennis surface: (1) a pre- and post-skill test of
      groundstrokes and service; (2) the Loughborough Intermittent Tennis Test (4 min
      work plus 40 s recovery) to volitional fatigue. Body mass decreased by 1.5% (P <
      0.0001). Mean heart rates differed between rest, post-warm-up and all
      intermittent test values (P < 0.01), between the pre- and post-skill tests (P <
      0.0001) and between bouts and recoveries (P < 0.01). Peak blood glucose and
      lactate concentrations were 5.9 mmol l(-1) (50% into the intermittent tennis
      test) and 9.6 +/- 0.9 mmol x l(-1) (25% into the test) respectively. Mean time to
      volitional fatigue was 35.4 +/- 4.6 min. Groundstroke hitting accuracy decreased
      by 69% from start to volitional fatigue in the intermittent test (P < 0.01).
      Service accuracy to the right court declined by 30% after the intermittent tennis
      test. The results of this study suggest that fatigue was accompanied by a decline
      in some but not all tennis skills.

PMID- 12003277
TI  - Oxygen uptake kinetics in children and adults after the onset of moderate
      intensity exercise.
AB  - The literature suggests that the oxygen uptake (VO2) response to the onset of
      moderate-intensity exercise may be both mature from childhood and independent of
      sex. Yet the cardiorespiratory response to exercise and the metabolic profile of
      the muscle appear to change with growth and development and to differ between the
      sexes. The aim of this study was to investigate further changes in the VO2
      kinetic response with age and sex. Participants completed a series of no less
      than four step change transitions, from unloaded pedalling to a constant work
      rate corresponding to 80% of their previously determined ventilatory threshold.
      Each participant's breath-by-breath responses were interpolated to 1 s intervals,
      time aligned and then averaged. A single exponential model that included a time
      delay was used to analyse the averaged response following phase 1 (15 s).
      Participants with parameter confidence intervals more than +/- 5 s were removed
      from the sample; the results for the remaining 13 men and 12 women (age 19-26
      years), 12 boys and 11 girls (age 11-12 years) were used for statistical
      analysis. Children had a significantly shorter time constant than adults, both
      for males (19.0+/-2.0 and 27.9+/-8.6 s respectively; P<0.01) and females (21.0+/
      5.5 and 26.0+/-4.5 s respectively; P<0.05). There were no significant differences
      in the time constant between the sexes for either adults or children (P>0.05). A
      significant relationship between the time constant and peak VO2 was found only in
      adult males (P<0.05). A shorter time constant in children may reflect an enhanced
      potential for oxidative metabolism.

PMID- 12003278
TI  - The use of heuristics during route planning by expert and novice orienteers.
AB  - Expert orienteers have reported using two heuristics when planning routes to
      points in the environment that must be located, known as 'controls'. These
      heuristics constitute attending to the start first and subsequently planning
      forward to a given control, and attending to the control first and planning
      backwards to the start. The aim of this study was to establish which heuristic
      experts use predominantly and whether novices' use of these heuristics differs
      from that of experts. Two methods for tracing attention were used while 20 expert
      and 20 novice orienteers planned routes in the laboratory. The results were used
      to infer the use of heuristics. The orienteers were also interviewed about
      planning. We found that, when planning, experts generally attend to the control
      first and novices to the start first. There was also some evidence that novices
      work forwards from the start to the control and that experts work backwards from
      the control to the start. From the interviews, it would appear that experts
      regard the location of the control as the crux of the problem and prioritize this
      area during planning. These results have implications for an understanding of
      expertise and problem-solving in sport.

PMID- 12003279
TI  - The menstrual cycle and its effect on the immune status of female endurance
      runners.
AB  - Twenty highly trained, eumenorrhoeic female endurance runners were studied over
      three consecutive menstrual cycles. Average training distance per week, total
      years training and mood states were recorded throughout the three cycles.
      Salivary progesterone and menstrual cycle diaries were recorded over the first
      two cycles to identify luteal phase onset and the presence of any menstrual
      irregularities. Saliva samples were collected daily over the third cycle for
      analysis of immunoglobulin A (IgA) concentration and secretion and saliva flow
      rate. Two-way analysis of variance (ANOVA) revealed no significant differences in
      mood states across the phases of the menstrual cycle (P > 0.05). Training logs
      indicated that training did not alter throughout the 3 month study. One-way ANOVA
      revealed no significant differences in IgA concentration (P = 0.92), secretion
      rate (P = 0.84) or saliva flow rate (P = 0.95) across the phases of the menstrual
      cycle. Pearson's product-moment correlation revealed no relationship between IgA
      concentration and progesterone between the phases of the cycle (r = 0.39). We
      conclude that, in ovulatory female endurance runners whose physical and emotional
      stress are stable, IgA concentration is not significantly affected by
      fluctuations in progesterone during the menstrual cycle.

PMID- 12003280
TI  - The effects of frequency of encouragement on performance during maximal exercise
      testing.
AB  - The aim of this study was to determine the effects of frequency of verbal
      encouragement during maximal exercise testing. Twenty-eight participants (12
      males, 16 females) aged 20.9 +/- 1.5 years (mean +/- s) performed a maximal
      exercise test (VO2max) on a treadmill without any verbal encouragement. The
      participants were matched according to their pre-test VO2max and placed into
      either a control group or one of three experimental groups. They performed a
      second exercise test (post-test) 1 week later. During the second test, the
      control group received no verbal encouragement; the 20 s (20E), 60 s (60E) and
      180 s (180E) encouragement groups received verbal encouragement every 20, 60 and
      180 s, respectively, beginning with stage 3 of the exercise test. Relative
      VO2max, exercise time, blood lactate concentration, respiratory exchange ratio
      (RER) and ratings of perceived exertion (RPE) were not significantly different
      from the first test to the second test for the control group without verbal
      encouragement and the 180E group that received infrequent encouragement. Post
      test values were significantly higher than pre-test values for the 20E and 60E
      groups. The post-test values of the 20E group were significantly higher than
      their pre-test values for relative VO2max (P < 0.001), exercise time (P <
      0.0001), blood lactate concentration (P < 0.05), RER (P < 0.01) and RPE (P <
      0.0001); this was also the case for the 60E group for relative VO2max (P < 0.01),
      blood lactate concentration (P < 0.05), RER (P < 0.05) and RPE (P < 0.05). The
      results suggest that frequent verbal encouragement (every 20 s and 60 s in the
      present study) leads to significantly greater maximum effort in a treadmill test
      than when no encouragement is given or when the encouragement is infrequent (i.e.
      every 180 s).

PMID- 12003281
TI  - The type, amount, frequency and timing of dietary supplement use by elite players
      in the First Spanish Basketball League.
AB  - The aims of this study were to determine the type, frequency and amount of
      dietary supplement consumption among a group of professional basketball players.
      The type, amount and specific timing of supplement use were recorded by 55
      professional basketball players from seven different teams of the First Spanish
      Basketball League. Most participants (58%) consumed dietary supplements.
      Multivitamins and vitamins were the most frequently used supplements among the
      athletes (50.9%), followed by sport drinks (21.8%), miscellaneous supplements
      (21.8%), amino acids (14.5%), proteins (12.7%) and carbohydrates (12.7%). The
      average daily dietary supplement was one capsule of multivitamins, one capsule of
      antioxidant vitamins, 0.2-1.0 g vitamin C, 10.3 g protein, 1.9 g amino acids,
      16.2 g carbohydrates and 377 ml of a commercial sport drink. Although the
      proportion of participants who consumed dietary supplements before, during and
      immediately after exercise was 25.4%, 16.3% and 7.3% respectively, only a few
      consumed a potentially ergogenic supplement at these times. It would appear
      unlikely that the type or amount of dietary supplements consumed had a beneficial
      effect on the physical performance of these professional basketball players, with
      the possible exception of antioxidant vitamins and the commercial sport drinks.

PMID- 12003282
TI  - Apology. Development and validation of a mood measure for adolescents.

PMID- 12003283
TI  - The relationship between reading beauty and fashion magazines and the use of
      pathogenic dieting methods among adolescent females.
AB  - This study examined the relationship between reading women's beauty and fashion
      magazines and the use of pathogenic dieting methods (laxatives, appetite
      suppressants/diet pills, skipping two meals a day, intentional vomiting, and
      restricting calories to 1,200 or less each day) among 502 high school females.
      Weak to moderate positive associations were found between reading frequency and
      each of these unhealthful practices except the use of laxatives. When controlling
      for anxiety about weight and frequency of regular exercise, however, the original
      bivariate relations between reading frequency and skipping two meals a day, and
      reading and intentional vomiting, disappeared. Replication and weak specification
      effects were found when examining the relationships between reading and taking
      appetite suppressant/weight control pills, and reading and restricting calories,
      under the control conditions. These findings suggest that two of the most common
      adolescent dieting methods--restricting calories and taking diet pills--appear to
      be influenced by the reading of women's beauty and fashion magazines.

PMID- 12003284
TI  - Talking about the silent fear: adolescents' experiences of violence in an urban
      high-rise community.
AB  - The self-reported violent experiences of adolescents living in a public
      subsidized urban high-rise building were examined. This effort was part of an
      interdisciplinary, community-university collaboration program called the HOME
      (High-rise On-site Multifamily Environments) Family Support Project. A survey of
      violent experiences and a one-on-one structured interview were conducted with 20
      adolescent residents. Results of the quantitative and qualitative analyses
      revealed high degrees of exposure to violence among these adolescents, concerns
      for their personal safety, as well as insights into what they believe adults
      could and should be doing to address increasing levels of community violence. The
      implications of these results for conducting ecologically valid research on
      sensitive issues with adolescents and for family support program planning are
      discussed.

PMID- 12003285
TI  - Adolescents' parent and peer relationships.
AB  - High school seniors (N = 89) from a suburban private high school were
      administered a comprehensive questionnaire to determine differences between
      adolescents who rated the quality of their parent and peer relationships as high
      or low. Adolescents with high parent and high peer relationship scores had more
      friends, greater family togetherness, lower levels of depression and drug use,
      and a higher grade point average.

PMID- 12003286
TI  - Evaluating the success of Caucasian fathers in guiding adolescents.
AB  - The purpose of this study was to identify guidance strengths and learning needs
      of fathers of adolescents. Perceptions of two generations were used to determine
      how well fathers perform as parents and realms of knowledge they have yet to
      acquire. The Parent Success Indicator, a 60-item Likert-type instrument, was
      administered to 126 Caucasian fathers and 185 adolescents. Significant
      differences obtained between generations for the total inventory, some scales,
      and many items. The amount of time spent together had the greatest influence on
      how both generations evaluated father success. Findings are discussed in terms of
      developing a curriculum to enhance the success of fathers.

PMID- 12003287
TI  - Child sexual abuse: offenders, disclosure, and school-based initiatives.
AB  - Children are being sexually abused at an alarming rate. Prevalence estimates
      suggest that one out of four girls and one out of ten boys experience sexual
      abuse. This paper examines the devastating impact of child sexual abuse and
      explores the contributions of school-based interventions to remedy the problem.

PMID- 12003288
TI  - Sources of support and psychological distress among academically successful inner
      city youth.
AB  - Study 1 examined the relationships between parental attachment, academic
      achievement, and psychological distress among a multiethnic sample of
      academically successful inner-city high school students (19 White, 54 Black, 9
      Asian, 18 Hispanic). These students participated in an enrichment program
      designed to prepare high school students for college success. The results suggest
      that the affective quality of maternal attachment is positively associated with
      grade point average, and the affective quality of paternal attachment is
      negatively associated with depressive symptoms. In Study 2, case examples provide
      an examination of sources of support, life stress, and patterns of resilience.
      Implications for prevention and intervention are also discussed.

PMID- 12003289
TI  - Profile of problem children from a rural county in Indiana.
AB  - In order to better identify and understand problems experienced by delinquent
      children and adolescents in a rural county in Indiana, in-the-trenches
      professionals working with these children were interviewed. Comparisons are drawn
      between observations of these professionals and existing research findings
      regarding Disruptive Behavior Disorders (i.e., ADHD, ODD, CD).

PMID- 12003290
TI  - Adolescent psychosocial maturity and alcohol use: quantitative and qualitative
      analysis of longitudinal data.
AB  - Based on a psyschosocial developmental framework, this study used a mixed model
      design, including both quantitative and qualitative methods, to examine the
      relationship between adolescents' psychosocial maturity and their alcohol use. A
      sample of 1,198 10th-grade students (51% female) was surveyed and followed up two
      years later. Both concurrent and longitudinal findings indicated that the more
      psychosocially mature adolescents were less likely to drink heavily than those
      who showed less maturity. At age 15 this relationship was even stronger for those
      whose peers also drank. Further, at age 17, this linear relationship was more
      pronounced for those who drank less heavily at age 15. Of the three psychosocial
      competencies examined, the construct of personal meaning was more strongly
      related to adolescent alcohol use than were the constructs of interpersonal
      understanding and interpersonal skills. To illustrate this construct, two of the
      adolescents were interviewed, a girl and a boy, individually at the end of both
      school years. Thematic and developmental analyses of the interviews revealed
      individual variations in how the adolescents made meaning of their drinking;
      these encourage speculations that go beyond the general pattern found in the
      study.

PMID- 12003291
TI  - Relationship between poverty and health among adolescents.
AB  - Although the effect of low socioeconomic status on the health of adolescents has
      been documented, the mechanism by which this occurs is not well understood.
      Furthermore, improving adolescent health through public health policy typically
      requires the presence of one or more modifiable risk factors which can be
      targeted for intervention. In spite of the well-documented negative associations
      between poverty and health, few modifiable risk factors have been identified.
      This study used the Evans-Stoddart Model of Health and Well-Being as a framework
      to examine data on 1,759 adolescents, aged 12 to 19, collected as part of the
      1994 National Population Health Survey. Results not only confirm the relationship
      between income and health, but suggest how the pathway operates through the
      social environment, lifestyle differences, access to health care, and a reduced
      sense of self-esteem and self-mastery. Bivariate and multivariate analyses found
      positive associations between physical activity levels and self-esteem and
      mastery. We interpret these findings as preliminary evidence that it might be
      possible to buffer the impact of poverty on health through policies which
      increase physical activity levels among those living in poverty. Such policies
      could also include a secondary goal of increasing the activity levels among
      inactive adolescents who are not living in poverty, as they will derive benefits
      from this increase, both psychologically and physiologically.

PMID- 12003292
TI  - Difficulties and coping strategies of Chinese, Japanese, and Korean immigrant
      students.
AB  - An exploratory study was conducted to investigate mental health concerns and
      coping strategies in a sample of 274 Chinese, Japanese, and Korean immigrant
      junior high and high school students. Participants responded to two open-ended
      questions relating to difficulties associated with coming to the United States
      and attendant coping strategies. Data were coded into several categories, and chi
      square and logistic regression analyses were conducted. Results indicated that
      the most common problem across all three Asian immigrant groups was communication
      difficulties. The most frequently reported coping strategy was the use of social
      support networks. In addition, Japanese students were more likely to experience
      interpersonal problems than were their Chinese and Korean counterparts. Korean
      students tended to utilize religious practices as a coping strategy more than did
      Chinese and Japanese students. The implications for research and counseling are
      discussed.

PMID- 12003293
TI  - The relationship between STD locus of control and STD acquisition among
      adolescent girls.
AB  - This longitudinal study examined adolescent girls' perception of control over
      sexually transmitted disease (STD) acquisition. Participants were asked questions
      regarding their perception of their STD locus of control (internal control;
      control by parents, partners, peers, and health care providers; and chance) at
      two waves of data collection. Of the 116 participants (mean age = 17 years), 82%
      were African-American and 18% were Caucasian. Responses to the measure of locus
      of control were significantly correlated across a 6-month interval. The responses
      regarding internal control, control by partner, and chance were not related to
      the acquisition of an STD in the next 6 months. Further, they were not influenced
      by an STD in the preceding 6 months. These results indicate that responses to a
      locus of control measure were stable over a 6-month period, and internal,
      partner, and chance locus of control perceptions seem to be neither determined by
      STD experience nor directly related to future STD acquisition. However,
      understanding an individual's locus of control may be helpful in providing
      appropriate counseling. Future research could examine how adolescent girls form
      their perceptions of control over STD acquisition.

PMID- 12003294
TI  - Differences between students' estimated and attained grades in a first-year
      introductory psychology course as a function of identity development.
AB  - Two hundred sixty-eight first-year university students were surveyed about the
      state of their identity development and their perceptions regarding chances for
      academic success in an introductory psychology course. In general, it was found
      that students who had an adult identity had a more accurate assessment of their
      chances for success in the course and also used more efficient study strategies.
      Students who had not completely formed an adult identity, however, were more
      inaccurate in estimates of their final grades and also seemed to use less
      productive study strategies. It was concluded that those who have formulated an
      adult identity might have also developed a more complete understanding of both
      themselves and their situation. Implications of the findings for further research
      regarding the effects of identity development on university life, as well as the
      implications for academic intervention programs, are discussed.

PMID- 12003295
TI  - Interleukin-8 levels in children with bacterial, tuberculous and aseptic
      meningitis.
AB  - OBJECTIVE: lnterleukin-8 (IL-8) is produced in monocytes and vascular endothelial
      cells in response to stimulation with bacteria or lipopolysaccharides, and is
      released from these cells into blood stream or tissue fluid. METHODS:
      Cerebrospinal fluid (CSF) levels of interleukin-8 in 56 children with
      nonbacterial, bacterial and tuberculous meningitis (TBM), and in 15 control
      subjects were analyzed to evaluate the involvement of this cytokine in the
      pathogenesis acute bacterial meningitis and their discriminative value between
      different etiologies of meningitis. The kinetics of IL-8 concentrations during
      the course of bacterial meningitis was also evaluated in patients. IL-8 levels
      were significantly higher in bacterial and TBM than in aseptic meningitis and in
      control subjects (p < 0.0001). RESULTS: There was no difference in the levels of
      IL-8 between the non-bacterial meningitis and control groups. The analysis of the
      kinetics of production of IL-8 in patients with bacterial meningitis showed that
      the SSF concentrations of this cytokine decreased to undetectable values in
      recovery stage. Conversely in patients with TBM the concentrations of IL-8 were
      elevated in two weeks after beginning the specific treatment. CONCLUSION: The
      results suggest that determining IL-8 levels may be useful in the differential
      diagnosis.

PMID- 12003296
TI  - Myringoplasty for chronic otitis media.
AB  - METHODS: 25 children in the age group of 8-14 years suffering from chronic
      suppurative otitis media were taken up for myringoplasty using onlay technique
      under general anaesthesia. RESULTS: All selected cases had a central type of dry
      perforation, good cochlear reserve and healthy middle ear mucosa. Cases having
      enlarged adenoids, infection in nose or throat, any traumatic perforation or
      previous attempt at closure were excluded from the study. It was found that there
      was 76% take up of graft after two months who also had improvement in hearing.
      CONCLUSION: We conclude that myringoplasty stands a good chance in children.

PMID- 12003297
TI  - Leukemia in infants.
AB  - OBJECTIVE: Acute Leukemia is rare in infants. It is characterized by non-specific
      symptomatology requiring a high index of suspicion on the part of a pediatrician
      for referral and diagnosis. It has peculiar biological features, unresponsiveness
      to treatment and poor prognosis. METHODS: Eighteen infants with acute leukemia
      were seen during 1994 to 2001 and were analyzed on the basis of clinical and
      laboratory data. There were 13 cases of Acute Lymphoblastic Leukemia (ALL), 4
      cases of Acute Myeloid Leukemia (AML) and one case remained unclassifiable, as
      the surface markers could not be done. Morphologically 9/13 cases of ALL were of
      FAB L1 type and remaining of L2 subtype, and 2/4 cases of AML were of FAB M1 type
      and remaining of M2 subtype. RESULT: Clinical data was available completely only
      in 11 cases. Hyperleucocytosis was present in 4 cases, organomegaly in 8 cases
      and lympadenopathy in 5 cases. One patient presented with a chloroma in the
      retrorbital region although there was no parenchymal involvement of the brain.
      Immunophenotyping could be done in 13 cases, where 7 cases were diagnosed as
      CALLA positive-ALL (HLADR+, CD19+, CD10+), 2 cases as Early Pre-B ALL (HLADR+,
      CD19+, CD10 negative), one as T ALL (cCD3+, CD2+, CD7+) and 3 cases as AML
      (CD13+, CD33+, HLADR+). None of our patients received treatment.

PMID- 12003298
TI  - Maximal expiratory pressure in residential and non-residential school children.
AB  - OBJECTIVE: Maximal Expiratory Pressure (MEP) is a powerful indicator for
      respiratory muscle strength, which reflects the ability of a person to cough
      effectively. METHODS: The present study was designed on healthy respiratory
      symptom free children of a Residential - Sainik (50) and Non-Residential (44)
      school children (aged 12-14 yrs) of Bijapur, to evaluate MEP in relation to their
      physical anthropometry. MEP (mm Hg) was determined by using a modified Black's
      apparatus, which is significantly higher in Residential-Sainik school children in
      comparison to Non-Residential school children (p < 0.01). RESULTS: In both
      groups, MEP showed positive correlation with height (Residential, r = 0.72, p <
      0.001; Non-Residential, r = 0.73, p < 0.001); weight (Residential, r = 0.73, p <
      0.001; Non-Residential, r = 0.69, p < 0.001), BSA (Residential, r = 0.79, p <
      0.001; Non-Residential, r = 0.72, p < 0.001) and BMI (Residential, r = 0.48, p <
      0.01; Non-Residential, r = 0.34, p < 0.05), and also revealed a higher MEP in
      children with greater chest expansion. CONCLUSION: Possibly, routine physical
      exercise in residential Sainik school children attribute to their better
      respiratory muscle strength.

PMID- 12003299
TI  - Allergy [editorial].

PMID- 12003300
TI  - Respiratory allergy.
AB  - Allergic rhinitis (AR) and asthma are common respiratory allergic disorders which
      are increasing globally more in developed countries. Although much has been
      written about childhood asthma and guidelines published by various international
      and national fora, not much information is available on AR. This is most common
      in children, is a significant risk factor for developing asthma, is a common
      comorbidity with asthma and affects quality of life. This paper highlights the
      risk factors for developing respiratory allergy asthma and AR, linkages between
      them and the management issues, particularly in relation to the allergic or
      allergological aspects as they have important bearing on management of children
      suffering from respiratory allergy. Specific immunotherapy (SIT) is re-emerging
      as useful therapy which alone has the potential to modify the natural history of
      disease and prevent the 'allergic march'. Timely diagnosis, correct management
      including timely referrals can ensure good quality life for those suffering from
      respiratory allergies.

PMID- 12003301
TI  - Common environmental allergens causing respiratory allergy in India.
AB  - Respiratory allergy affects all age groups but the children are the worst
      affected by the respiratory allergy. Bioparticles from different biological
      sources are the main cause of allergy. Pollen grains, fungal spores, insect and
      other materials of biological origin form the most important allergen load in the
      air. For the efficient diagnosis of the allergy and its effective treatment it is
      very important to know about the prevalence, seasonal and annual variations of
      aeroallergens of the area. India being the climatically diversed country, there
      is diversity in the flora and fauna of different parts of the country.
      Atmospheric surveys carried out in different parts of India reveal that, Alanus
      nitida, Amarantus spinosus, Argemone mexicana Cocos nucifera, Betula utilis,
      Borasus flabellifer, Caraica papaya, Cedrus deodara, Cassia fistula, Parthenium,
      Chenopodium album, Dodonaea viscosa, Malotus phillipensis, Plantago ovata,
      Prosopis juliflora, Ricinus communis, Holoptelea intergifolia are the
      allergenically important pollens of the country. Among the fungal aeroallergens,
      Alternaria, Candida aibieans, Aspergillus versicolor, Aspergillus terreus,
      Aspergillus japonicus, Cladosporium cladosporoides, Fusarium roseum, Ganoderma
      lucidum,Neurospora sitophila Helminthosporium, Ustilago trtici, Uromyses are
      important allergens. Dust mites D. farinae, D.pteronyssinus are also important
      source of inhalant allergens particularly in the coastal areas of the country.
      Cockroaches, beetles, weevils, mosquitoes, house flies also contribute towards
      the aeroallergen load and are allergenically implicated. Avoidance of the indoor
      and outdoor aeroallergens is recommended for better management of respiratory
      allergy.

PMID- 12003302
TI  - Food allergy.
AB  - Allergic disease is a major contributor to illnesses and mortality worldwide.
      Food hypersensitivity is often the first phenomenon in the allergic march that
      includes gastroenteropathy, eczema, asthma and hay fever. Recent evidence
      indicates that prevention of food hypersensitivity in early life is associated
      with reduction in the incidence of eczema and asthma in later childhood.
      Strategies for prevention include exclusive breast feeding, restriction of
      mother's diet during lactation, hydrolyzed formula, delayed introduction of
      allergenic solid foods and reduced exposure to house dust mites and tobacco
      smoke. This is a highly cost-beneficial and cost-effective approach.

PMID- 12003303
TI  - Prevention of atopic disorders.
AB  - Prevention of sensitization, onset of disease and disease exacerbations is a very
      important aspect of holistic approach towards allergic disorders. The prevalence
      of allergic or atopic disorders has increased significantly in children over the
      last three decades. There are significant variations in prevalence between
      countries and also within many countries. Environmental factors obviously play a
      major role. Environmental allergens are responsible for sensitisation, disease
      and exacerbations of disease symptoms. Preventive strategies at each level are
      important: Primary prevention is to stop the process of sensitisation and
      secondary prevention to prevent re-exposures or prolonged exposure in those who
      have become sensitized while tertiary prevention is to reduce or minimise
      morbidity. Various allergen avoidance measures are discussed, with reference to
      India so that physicians can incorporate these in the management not only of
      atopic patients but also as preventive strategy in high risk families.

PMID- 12003304
TI  - Localised gastric ileus in Klebsiella sepsis.

PMID- 12003305
TI  - Idiopathic arterial calcification in infancy, pathology, diagnosis and treatment
      modalities.

PMID- 12003306
TI  - Congenital ganglioglioma.
AB  - Congenital neoplasms of brain presenting at birth are extremely uncommon. We
      report a case of congenital ganglioglioma presenting at birth with hydrocephalus.
      Ventriculoperitoneal shunt and surgical debulking of the tumour along with
      histopathological confirmation were done at 6 months of age. On follow-up at 18
      months, the child's hydrocephalus is static and his assessed developmental age is
      10-12 months.

PMID- 12003307
TI  - Persistent hyperinsulinemic hypoglycemia of infancy--successful therapy with
      nifedipine.
AB  - Recent studies have demonstrated a role for calcium channel blocking agents in
      the treatment of persistent hyperinsulinemic hypoglycemia of infancy. We report a
      30 day old infant with PHHI whom we successfully treated with oral nifedipine
      alone.

PMID- 12003308
TI  - Unusual foreign bodies in nasopharynx and bronchus.

PMID- 12003309
TI  - Use of wastewater as a nutrient solution in a closed gravel hydroponic culture of
      giant reed (Arundo donax).
AB  - The objective of this experimental work was to examine the efficiency of giant
      reed (Arundo donax L.), as a source of biomass production and as a biofiltering
      device for sewage effluents. Two giant reed populations were cultivated in a
      closed gravel hydroponic system, where pig's waste was used as a nutrient
      solution. The results showed that stem biomass production varied from 12 to 23 kg
      DM m(-2) yr(-1), more than the ordinary production in the soil. According to stem
      analysis, for the first two years, there was an average infiltration rate of 31 g
      m(-2) yr(-1) total N, 7.5 g m(-2) yr(-1) total P, 18.8 g m(-2) yr(-1) K, 2.1 g m(
      2) yr(-1) Ca, 2.1 g m(-2) yr(-1) Mg, 0.27 g m(-2) yr(-1) Fe, 0.02 g m(-2) yr(-1)
      Mn, 0.14 g m(-2) yr(-1) Zn and 0.08 g m(-2) yr(-1) Cu. During the third year,
      when a nutrient solution with added P was used, the average infiltration rate for
      most elements increased by 46% and for P by 169%.

PMID- 12003310
TI  - Improving laccase production by employing different lignocellulosic wastes in
      submerged cultures of Trametes versicolor.
AB  - Laccase production by the white-rot fungus Trametes versicolor (CBS100.29) grown
      in submerged cultures was studied. Addition of different insoluble
      lignocellulosic materials into the culture medium in order to enhance laccase
      production was investigated. The lignocellulosic materials were grape seeds,
      grape stalks and barley bran, selected because of their availability and low
      cost, since they are agro-industrial wastes abundant in most countries. Barley
      bran gave the highest activities, a maximum value of 639U/l, which was 10 times
      the value attained in the cultures without lignocellulosics addition. The
      decolourisation of a model dye, Phenol Red, by the ligninolytic fluids obtained
      in the above-mentioned cultures was investigated. Grape stalk and barley bran
      cultures showed the highest ability to decolourise the dye, attaining a
      percentage of decolourisation of around 60% in 72 h.

PMID- 12003311
TI  - Anaerobic digestion of alcohol sulfate (anionic surfactant) rich wastewater-
      batch experiments. Part I: influence of the surfactant concentration.
AB  - Textile wet processing wastewater (e.g., from cotton desizing) contains high
      concentrations of surfactants as well as readily biodegradable compounds like
      starch and other carbohydrates. Decyl sulfate (DS, surfactant) and soluble starch
      were used as model pollutants for biodegradation batch experiments. Very high
      loadings of the biomass were applied (DS: 21.7-217 g/kg cell dry weight (CDW);
      starch: 910 g/kg cell dry weight) to study inhibitory effects of the surfactant
      on the degradation cascade of the biopolymer. The starch hydrolysis was inhibited
      above sludge loadings of 65 g DS/kg CDW. Acidogenesis was the degradation step
      with the highest resistance towards inhibitory effects of the surfactant, whereas
      methanogenesis proved to be the most sensitive. The effects of the surfactant
      were described by the change of the methane evolution, which was reduced by 50%
      in 87 days with an addition of 58 g DS/kg CDW. The surfactant caused a high
      temporary accumulation of intermediates like volatile fatty acids. At the highest
      loading (217 g DS/kg CDW) the conversion of the substrate to methane was only
      minor.

PMID- 12003312
TI  - Anaerobic digestion of alcohol sulfate (anionic surfactant) rich wastewater-
      batch experiments. Part II: influence of the hydrophobic chain length.
AB  - High-strength wastewater of some industries contains high concentrations of
      surfactants and readily biodegradable compounds like starch and other
      carbohydrates. Wastewater of this type is found in the textile wet-processing
      industry (e.g., cotton desizing). The anaerobic degradation process in such
      wastewater is inhibited due to the high surfactant content. Alcohol sulfate (AS)
      of increasing hydrophobic chain length (C8 to C18, surfactant) and soluble starch
      (size) were used as model compounds in a series of batch experiments with high
      loadings of the biomass (65 g AS/kg cell dry weight; 910 g starch/kg cell dry
      weight). The strongest inhibition of the hydrolysis, acidogenesis and
      acetogenesis was found in reactors containing medium chain ASs like dodecyl
      sulfate. Starch hydrolyzation rates decreased by nearly 90% in the presence of
      dodecyl sulfate. Decyl sulfate caused the strongest inhibition of the
      methanogenesis and a decrease of the methane evolution by 75% within 87 days
      experimental time. It was found that short as well as long chain ASs caused only
      minor inhibition phenomena. The presented data can be used as a basis for the
      selection of suitable surfactants that do not (or not seriously) inhibit the
      anaerobic digestion of industrial effluents.

PMID- 12003313
TI  - Bio-degradation of lignin in olive pomace by freshly-isolated species of
      Basidiomycete.
AB  - The solid waste (pomace) from olive oil processing cannot be used directly as an
      animal feed, but it was thought that an appropriate series of fermentations might
      improve its nutritional value. As a first step, typical samples of pomace were
      subjected, after an alkaline pre-treatment, to delignification by Phanerochaete
      chrysosporium (ATCC 19343), Oxysporus sp., Schizophyllum commune, Hyphoderma sp.
      or Ganoderma sp.; the last four species being freshly isolated from decaying wood
      collected in a woodland in Jordan. The relative activity of the species was
      judged by the levels of ligninase or laccase secreted and the extent of lignin
      degradation under a range of experimental conditions. Oxysporus sp. (ca. 69%) and
      S. commune (ca. 53%) gave significantly higher levels of breakdown of the
      lignified material than the other recent isolates. P. chrysosporium (ca. 60%) was
      not as active as in previously reported studies, and it may be that culturing the
      fungus on a standard laboratory medium had reduced its ability to generate
      ligninase. Further work is needed to establish whether the delignified pomace
      could be further processed into a feed for poultry.

PMID- 12003314
TI  - Dye biosorption sites in Aspergillus niger.
AB  - Aspergillus niger is capable of removing dyes from an aqueous solution. In the
      study, the roles played by three major functional groups: carboxyl, amino and
      phosphate, and the lipid fraction in the biomass of A. niger in biosorption of
      four dyes, Basic Blue 9, Acid Blue 29, Congo Red and Disperse Red 1, were
      investigated. These functional groups in A. niger were chemically modified
      individually to determine their contribution to the biosorption of dyes. It was
      found that biosorption of dyes was influenced by the functional groups in the
      fungal biomass and the chemical structure of the dyes.

PMID- 12003315
TI  - Capacity of various experimental diets to support biomass and reproduction of
      Perionyx excavatus.
AB  - Biomass production and reproduction of a group of four adult Perionyx excaratus
      were studied in limited supplies of four experimental diets; cowdung alone and
      its mixtures with straw, bamboo leaf litter or kitchen waste, in order to select
      a suitable diet medium for vermiculture. P. excavatus showed maximum rate of
      biomass increase and reproduction in the mixtures with straw and bamboo leaf
      litter. In spite of achieving the highest final biomass value. P. excavatus
      showed the lowest rate of biomass increase and reproduction in the mixture with
      kitchen waste. Cowdung, a natural food of P. excavatus, was marginally better
      than the mixture with kitchen waste with regard to the rate of biomass increase
      and reproduction.

PMID- 12003316
TI  - Anaerobic removal of linear alcohol ethoxylates.
AB  - The present paper deals with a laboratory-scale study of anaerobic treatment of
      two commercial mixtures (LS2, LT7) of alcohol ethoxylates with 8-14 carbon atoms
      and 2 and 7 ethoxy groups. Tests were carried out in batch, with a 2 g l(-1)
      single dose, and in semibatch, with daily 0.2 g l(-1) doses. The behaviour of the
      tested mixtures was different: anaerobic sludge adsorption was the main removal
      process for LS2, while adsorption was less significant and biodegradation was
      more important for LT7. These differences appeared to be mainly related to the
      ethoxy portion length determining the extent of biodegradability and adsorption.

PMID- 12003317
TI  - Enhancement of proteolytic enzyme activity excreted from Bacillus
      stearothermophilus for a thermophilic aerobic digestion process.
AB  - Proteolysis is one of the main enzymatic reactions involved in waste activated
      sludge (WAS) digestion. In this study, proteases excreted from Bacillus
      stearothermophilus (ATCC 31197) were classified, and an enhancement of protease
      activity was achieved using economical chemical additives for WAS digestion.
      Proteases excreted from B. stearothermophilus were classified into two families:
      serine and metallo-proteases. Various metal ions were investigated as additives
      which could potentially enhance protease activity. It was observed that Ca2+ and
      Fe2+ could markedly activate these enzymes. These results were applied to
      thermophilic aerobic digestion (TAD) of industrial WAS using B.
      stearothermophilus. The addition of these divalent ions enhanced the degradation
      performance of the TAD process in terms of reducing the total suspended solids
      (TSSs), the dissolved organic carbon (DOC) content, and the intracellular and
      extracellular protein concentrations. The best result, with respect to protein
      reduction in a digestion experiment, was obtained by the addition of 2 mM Ca2+.
      Therefore, a proposed TAD process activated by calcium addition can be
      successfully used for industrial and municipal WAS digestion to the upgrading of
      TAD process performance.

PMID- 12003318
TI  - Vermicomposting of different forms of water hyacinth by the earthworm Eudrilus
      eugeniae, Kinberg.
AB  - Six-month long trials were conducted on different vermireactors fed with one of
      the following forms of water hyacinth: (a) fresh whole plants, (b) dried whole
      plants, (c) chopped pieces of fresh plants, (d) 'spent' weed taken from reactors
      after extracting volatile fatty acids (VFAs), (e) precomposted fresh weed and (f)
      precomposted spent weed. The first four forms were studied with and without
      cowdung. The experiments revealed three clear trends (i) of the various forms of
      the weed assessed, the precomposted forms were the most favoured as feed by
      Eudrilus eugeniae, Kinberg, while the fresh whole form was the least favoured,
      (ii) the different forms of spent weed were favoured over the corresponding forms
      of fresh weed, and (iii) blending of cowdung (approximately 14% of the feed mass)
      with different forms of water hyacinth had a significant positive impact on
      vermicast output, growth in worm zoomass, and production of offspring relative to
      the corresponding unblended feed. In all reactors, the 'parent' earthworms
      steadily grew in size over the six-month span, and produced offspring. There was
      no mortality. The experiments thus confirm that water hyacinth can be sustainably
      vermicomposted in any of the forms with E. eugeniae.

PMID- 12003319
TI  - Effect of temperature, anaerobiosis, stirring and salt addition on natural
      fermentation silage of sardine and sardine wastes in sugarcane molasses.
AB  - Conditions for a natural fermentation during ensilage of sardines or their waste
      in sugarcane molasses (60:40 w/w) were evaluated regarding the effect of
      temperature (15, 25 and 35 degrees C), anaerobiosis (closed vs. open jars), daily
      stirring of the mixture, and salt addition to the initial mix at 5% (w/w) level.
      Successful natural fermentation took place in sardine silages incubated at 25 or
      35 degrees C in open jars to reach a pH of 4.4 in about 2 and 1 weeks,
      respectively. For samples kept at 15 degrees C, the pH decline was very slow and
      pH did not decrease below 5.5 after one month of incubation. At 25 degrees C, the
      most favorable conditions for silage of sardine waste in cane molasses, as
      evidenced by the fastest decline in pH to a stable value of about 4.4, were
      achieved in closed jars and with daily stirring of the mix. The pH 4.4 was
      reached in one week with an advance of at least 3 days compared to the other
      conditions (open jars and closed jars without daily stirring). Addition of salt
      at 5% (w/w) in the mix before incubation inhibited the fermentation process.

PMID- 12003320
TI  - High-temperature alcoholic fermentation of whey using Kluyveromyces marxianus
      IMB3 yeast immobilized on delignified cellulosic material.
AB  - A novel system for high-temperature alcoholic fermentation of whey is described.
      This system consists of Kluyveromyces marxianus yeast immobilized on delignified
      cellulosic material (DCM). The effect of pH, initial lactose concentration and
      temperature on the fermentation of a synthetic medium containing lactose was
      studied. Batch fermentations of whey were also carried out and the formation of
      volatile by-products was examined. The concentrations of higher alcohols were
      found to be in very low levels leading to a product of improved quality. The
      fermented whey had an improved characteristic aroma compared to unfermented whey.
      The possibility to use fermented whey as raw material for the production of a
      novel, low alcohol content drink was also investigated.

PMID- 12003321
TI  - The evaluation of enhanced nitrification by immobilized biofilm on a
      clinoptilolite carrier.
AB  - This study was conducted to evaluate the effect of clinoptilolite on
      nitrification in activated sludge (AS), and was focused on a relationship between
      ammonium exchange capacity of this mineral and improvement of nitrification. In
      batch experiments, the adsorption property of biofilm-attached clinoptilolite did
      not show substantial difference from that of natural clinoptilolite, indicating
      that bioregeneration became completely achieved without any regenerant in the AS.
      The AS with added clinoptilolite (ZR) was compared to the control AS (CR) when
      the ratio of chemical oxygen demand (COD) to total kjeldahl nitrogen (TKN) of
      influent, i.e. C/N ratio, was varied from 3.25 to 7.5 at a hydraulic retention
      time (HRT) of 3 h. Enhanced nitrification was comparatively observed for the ZR
      as C/N ratio gradually increased. The results indicated that the clinoptilolite
      provided a relatively low C/N ratio for nitrifiers, due to ammonium adsorption of
      this mineral, and consequently nitrification was accelerated.

PMID- 12003322
TI  - Preparation and characterisation of gelatine from the skin of harp seal (Phoca
      groendlandica).
AB  - This paper describes a method for extraction of gelatine from the skin of harp
      seal at mild acid conditions and gives a chemical and physical comparison of this
      gelatine with other mammalian and cod-skin gelatines. As compared to the wet
      weight of unhaired skin, a recovery of 11% dry gelatine was achieved after acid
      treatment and a two step water extraction at 60 and 75 degrees C. The chemical
      and physical properties of the gelatine were similar to the properties of
      commercial gelatines made from bovine and porcine skin, but significantly
      different from the properties of Atlantic cod-skin gelatine. The results
      indicated that seal skin gelatine can be used as a substitute for standard
      commercial gelatines for food technology applications.

PMID- 12003323
TI  - Rose hip (Rosa canina L.) oil obtained from waste hip seeds by different
      extraction methods.
AB  - From the rose hip seed, which is generally a waste material, valuable oil can be
      obtained for medicinal use. Various extraction methods have been compared:
      traditional solvent extraction with ultrasound-, microwave-, sub- and
      supercritical fluid extraction (SFE). Unsaturated fatty acid (UFA: oleic-,
      linoleic- and linolenic acid; 16.25-22.11%, 35.94-54.75%, 20.29-26.48%) and
      polyunsaturated fatty acid (PUFA:linoleic- and linolenic acid) content were over
      90% and 60% in the recovered oils. The oils contained different amounts of
      metals. The concentration of some metals, particularly iron in microwave oil
      (27.11 microg g(-1)) is undesirable from the aspect of stability. By traditional
      solvent extraction, oil was obtained in 4.85 wt/wt%. Subcritical FE appeared to
      be the best method for the recovery of rose hip oil with highest oil yield (6.68
      wt/wt%), carotene- (145.3 microg g(-1)) and linoleic acid content (54.75%).
      Supercritical FE without organic solvent is suitable for mild recovery of oil.
      The oil was rich in UFA and PUFA (92.7% and 76.25%) and contained the lowest
      amount of carotene and pheophytin (36.3 and 45.8 microg g(-1)). Oil yield in most
      new extraction methods (microwave extraction, super- and subcritical FE) was
      higher than in the case of traditional Soxhlet extraction. The main benefit of
      supercritical FE with CO2 is the solvent free oil while in the case of other
      extractions evaporation of the solvent is needed. Although the content of
      bioactive compounds in oils was different, all oils may be appropriate for
      medicinal use.

PMID- 12003324
TI  - Larvicidal efficacy of Pavonia zeylanica L. and Acacia ferruginea D.C. against
      Culex quinquefasciatus Say.
AB  - Larvicidal efficacy of leaf extracts of Pavonia zeylanica and Acacia ferruginea
      were tested against the late third instar larvae of Culex quinquefasciatus. The
      larval mortality was observed after 24 h of treatment. The LC50 values of P.
      zeylanica and A. ferruginea were 2214.7 and 5362.6 ppm, respectively.

PMID- 12003325
TI  - The effects of certain antibiotics on biogas production in the anaerobic
      digestion of pig waste slurry.
AB  - Antibiotics commonly used in the treatment of pigs - amoxicillin trihydrate,
      oxytetracycline hydrochloride and thiamphenicol were added at different
      concentrations to aliquots of pig waste slurry plus anaerobic sludge in serum
      bottles. The biogas production and methane concentration in the headspace were
      monitored to determine the effect of the antibiotics on the anaerobic process.
      With thiamphenicol significant differences in methane production were found for
      concentrations of 80 and 160 mg l(-1) slurry. Compared to the control, only minor
      differences in methane production were noted in the bottles to which amoxicillin
      (60 and 120 mg l(-1)) had been added. Methane production was about the same for
      the bottles with different oxytetracycline concentrations (125 and 250 mg l(-1))
      and for the control.

PMID- 12003326
TI  - Role of carbon dioxide and ion transport in the formation of sub-embryonic fluid
      by the blastoderm of the Japanese quail.
AB  - 1. The explanted blastoderm of the Japanese quail was used to explore the role of
      ions and carbon dioxide in determining the rate of sub-embryonic fluid (SEF)
      production between 54 and 72 h of incubation. 2. Amiloride, an inhibitor of
      Na+/H+ exchange, at concentrations of 10(-3) to 10(-6) M substantially decreased
      the rate of SEF production when added to the albumen culture medium. N
      ethylmaleimide, an inhibitor of V type H+ ATPase, also decreased this rate but
      only to a small extent at the highest dose applied, 10(-3) M. Both inhibitors had
      no effect on SEF production when added to the SEF. 3. The inhibitors of cellular
      bicarbonate and chloride exchange, 4-acetamido-4'-isothiocyano-2,2'-disulphonic
      acid (SITS) and 4,4' diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), had no
      effect upon SEF production. 4. Ouabain, an inhibitor of Na+/K+ ATPase, decreased
      SEF production substantially at all concentrations added to the SEF (10(-3) to
      10(-6) M). Three sulphonamide inhibitors of carbonic anhydrase, acetazolamide,
      ethoxzolamide and benzolamide, decreased SEF production when added to the SEF at
      concentrations of 10(-3) to 10(-6) M. Benzolamide was by far the most potent.
      Neither ouabain nor the sulphonamides altered SEF production when added to the
      albumen culture medium. 5. Using a cobalt precipitation method, carbonic
      anhydrase activity was localised to the endodermal cells of the area vasculosa.
      The carbonic anhydrase activity was primarily associated with the lateral plasma
      membranes, which together with the potent inhibitory effect of benzolamide,
      suggests the carbonic anhydrase of these cells is the membrane-associated form,
      CA IV. 6. The changes in SEF composition produced by inhibitors were consistent
      with the production of SEF by local osmotic gradients. 7. It is concluded that a
      Na+/K+ ATPase is located on the basolateral membranes of the endodermal cells of
      the area vasculosa, and that a sodium ion/hydrogen ion exchanger is located on
      their apical surfaces. Protons for this exchanger would be provided by the
      hydration of CO2 catalysed by the membrane-associated carbonic anhydrase.
      Furthermore, it is proposed that the prime function of the endodermal cells of
      the area vasculosa is the production of SEF.

PMID- 12003327
TI  - Dietary L-carnitine increases plasma insulin-like growth factor-I concentration
      in chicks fed a diet with adequate dietary protein level.
AB  - 1. The effect of L-carnitine supplemented into experimental diets with varying
      dietary protein concentrations (50, 200 and 400 g/kg) on body weight gain and
      plasma insulin-like growth factor-I (IGF-I) concentration in chicks was examined.
      2. Dietary L-carnitine supplementation provided 0, 200, 500 and 1000 mg/kg.
      Chicks were given the diet ad libitum for 10 d. 3. When L-carnitine was provided
      as 500 or 1000 mg/kg, body weight gain was significantly improved in birds
      receiving the 200 and 400 g protein/kg diets. 4. There was an interaction between
      dietary L-carnitine and protein content on plasma IGF-I concentration. L
      carnitine supplementation had little influence on plasma IGF-I concentrations in
      birds receiving the low protein (50 g/kg) diet. When dietary L-carnitine
      concentrations were increased from 0 to 1000 mg/kg in the adequate protein (200
      g/kg) diet, plasma IGF-I concentrations were also increased. However, when
      dietary L-carnitine content was more than 500 mg/kg in the 400 g/kg protein
      group, plasma IGF-I concentration decreased with increasing dietary L-carnitine
      content. 5. Body weight change correlated significantly with the alteration in
      plasma IGF-I concentrations in chicks given diets with adequate dietary protein.
      6. In conclusion, the improvement in body weight gain caused by dietary L
      carnitine supplementation was achieved when chicks were given their dietary
      protein requirement, which may be partially explained by an increase in plasma
      IGF-I concentration.

PMID- 12003328
TI  - Intracerebroventricular injection of glucagon-like peptide-1 decreases monoamine
      concentrations in the hypothalamus of chicks.
AB  - 1. We measured the concentrations of dopamine (DA), norepinephrine (NE),
      epinephrine (E) and 5-hydroxytryptamine (5-HT) in the hypothalamus of 21-d-old
      male brown-egg layer-type chicks after intracerebroventricular injection of
      glucagon-like peptide-1 (GLP-1). 2. The monoamine concentrations of the whole
      hypothalamus, paraventricular nucleus and lateral hypothalamic area were not
      significantly affected by GLP-1. 3. However, concentrations of DA, NE and E, but
      not 5-HT, in the ventromedial hypothalamic nucleus (VMH) were significantly
      decreased by GLP-1. 4. These observations suggest that the anorexigenic effect of
      GLP-1 involves catecholaminergic systems in the VMH in the chick.

PMID- 12003329
TI  - Differences in composition of avian bone collagen following genetic selection for
      resistance to osteoporosis.
AB  - 1. Collagen characteristics were compared in the tibiotarsus and humerus from 103
      females and 38 males aged 68 to 72 weeks from the G6 generation of lines of
      laying hen selected for resistance or susceptibility to osteoporosis (high and
      low bone index (BI) lines). 2. Selection over the latest generation resulted in
      further divergence in the breaking strengths of humerus (from 12.3 to 21.8%) and
      tibia (from 22.3 to 37.3%) in hens. Males also showed line differences in bone
      strengths. 3. Plasma pyridinoline concentration was higher in hens in the low BI
      line, suggesting a greater rate of bone resorption in this line. 4. There were
      few differences between the lines in collagen and calcium concentrations in
      humerus and tibiotarsus cortical bone. 5. There were no differences between the
      lines in either sex in reduced immature collagen cross-link content of humerus or
      tibiotarsus. 6. Mature collagen cross-link content was higher in the high BI line
      in the male humerus but this effect was not apparent in the male tibiotarsus nor
      in either bone in the females. 7. Pyrrolic cross-link contents were higher in the
      high BI line in the female humerus and tibiotarsus and in the male tibiotarsus.
      8. Over both lines combined, there were positive correlations between humeral and
      tibiotarsal pyrrole contents and strengths in females and between tibiotarsal
      pyrrole content and strength in males. 9. It is concluded that an increase in
      cross-linking, particularly pyrrolic cross-linking, in the collagen matrix
      contributes in part to the improvement in bone strength in the high BI line.

PMID- 12003330
TI  - Eggshell conductance, embryonic growth, hatchability and embryonic mortality of
      broiler breeder eggs dipped into ascorbic acid solution.
AB  - 1. Eggs from a broiler breeder flock between 25 and 29 weeks of age were dipped
      into solutions of various concentrations of ascorbic acid (AA) for up to 2 min,
      in order to evaluate its effects on eggshell conductance (EC), amniotic fluid pH,
      albumen height and pH, embryonic weight and hatchability. 2. Three experiments
      were conducted and the following treatments were used: control, non-dipped (CND);
      control, water-dipped (CWD); 10 g AA/l (AA1); 20 g AA/l (AA2) and 30 g AA/l
      (AA3). Measurements of EC before and after dipping were made in experiments 1 and
      2 in eggs from hens at 25 and 27 weeks of age, respectively. Albumen height and
      pH were measured after dipping the eggs in experiment 2. In experiment 3, egg
      weight loss, embryonic weight and amniotic fluid pH at 14 d of age, hatchability
      percentage (HP), and embryonic mortality were measured in eggs from hens at 29
      weeks of age. 3. AA treatment of eggs and dipping period of time (1, 1.5 and 2
      min) increased EC of eggs from hens at 25 and 27 weeks of age. 4. AA3 treatment
      for 2 min reduced albumen height and increased albumen pH of eggs when compared
      with the CND treatment in eggs from hens at 27 weeks of age. 5. HP of AA1-treated
      eggs from hens at 29 weeks of age was higher than that of the CND treatment. AA2
      and AA3 treatments of eggs reduced HP and increased the percentage of non-pips
      when compared with any of the other treatments. 6. AA2 and AA3 treatments of eggs
      increased egg weight loss when compared with the control treatments (CND and
      CWD). Dipping treatment did not influence amniotic fluid pH or embryo weight
      expressed as a percentage of initial egg weight. 7. It is concluded that dipping
      hatching eggs into AA solution increased EC of eggs. Dipping eggs into 10 g AA/l
      for a period of 2 min increased HP in eggs from hens at 29 weeks of age, although
      this was not associated with a significant increase in egg weight loss.

PMID- 12003331
TI  - The effect of early-age food restriction on heat shock protein 70 response in
      heat-stressed female broiler chickens.
AB  - 1. This study was conducted to determine the effect of early-age food restriction
      on heat shock protein (hsp) 70 synthesis in the brains of female broiler chickens
      exposed to high ambient temperatures. 2. Chicks were brooded for 3 weeks and then
      maintained at 24+/-1 degrees C. 3. On d 0, chicks were assigned to one of 4
      feeding regimens; each regimen was applied to 4 cages of chicks. The regimens
      were: (1) ad libitum feeding (AL); (2) 80% food restriction at 4, 5 and 6 d of
      age (F80); (3) 60% food restriction at 4, 5, and 6 d of age (F60); and (4) 40%
      food restriction at 4, 5 and 6 d of age (F40). From d 35 to d 41, all chicks were
      subjected to 38+/-1 degrees C for 2 h/d. 4. One day following food restriction (d
      7), hsp 70 expression in the brain samples of F60 and F40 chicks was augmented
      but not those fed AL and F80. 5. Prior to the heat challenge (d 35), all chicks
      had similar hsp 70 response. Irrespective of feeding regimen, there was a marked
      increase in hsp 70 expression after 4 d of heat treatment (d 38). Following 7 d
      of heat exposure (d 41), except for the F60 chicks, the augmented hsp 70
      expression in the brains of AL, F80 and F40 birds was not maintained. 6.
      Enhancement of hsp 70 expression was noted in birds subjected to F60, but not AL,
      F80 or F40, throughout the period of heat exposure.

PMID- 12003332
TI  - Influence of mating sex ratio in commercial pheasant flocks on bird health and
      the production, fertility, and hatchability of eggs.
AB  - 1. The effects of two mating ratios (8:1 and 12:1 females:males) on bird health,
      egg production and quality, fertility (employing macroscopic and microscopic
      techniques) and hatchability were examined for pheasants (Phasianus colchinus) on
      a commercial game farm, to provide a baseline data set for production of
      pheasants under specific conditions. 2. Mating ratio did not significantly affect
      mortality or pathology of breeding birds. 3. Egg production was significantly
      higher for the 8:1 mating ratio over the first 5 weeks of the trial but this
      difference disappeared during the second half of the trial. 4. Incidence of
      rejected eggs increased as the season progressed, mainly due to poor shell
      quality, but it was not significantly affected by mating ratio. 5. Fertility of
      eggs produced from birds under an 8:1 mating ratio was consistently and
      significantly 4% higher than fertility of eggs from the 12:1 mating ratio. The
      incidence of eggs showing no sign of mating (no sperm) was twice as high for the
      12:1 pens (13.7% of the sample). There was good agreement between macroscopic and
      microscopic examination of fertility in eggs. Higher fertility in the 8:1 pens
      appeared to be related to a higher proportion of the females being recruited and
      mated. 6. Hatchability was significantly improved by adopting an 8:1 mating
      ratio, presumably due to the higher fertility of the eggs. Candling of the eggs
      improved hatchability but only for the 12:1 pens probably because more clear eggs
      were removed from the tray.

PMID- 12003333
TI  - Heart growth in broilers.
AB  - 1. Morphological development of the heart in fast-growing, meat-type fowl of both
      sexes was studied. 2. In 4 experiments, fowl were weighed, killed and hearts were
      dissected at 0, 20, 34, and 48th d of age. Heart weight (HW), length (HL),
      diameter (HD), and thickness of the right ventricular wall (RVW) and left
      ventricular wall (LVW) were determined. 3. This is the first description of
      sexual dimorphic differences in the heart of fowl. 4. Results indicate that males
      have greater HW, HL, and LVW thickness than females. However, thickness of the
      RVW during the embryonic period, as indicated by thickness of the RVW at hatching
      in females, exceeds that of males.

PMID- 12003334
TI  - Effect of naked neck gene (NA) and frizzle gene (F) on immunocompetence in
      chickens.
AB  - 1. A total of 98 birds belonging to 4 genetic groups from two specialised
      populations--heterozygous naked neck (NA*NA/NA*N) and normally feathered
      (NA*N/NA*N) from one specialised population and heterozygous frizzle (F*F/F*N)
      and normally feathered (F*N/F*N) from another specialised population--were
      evaluated for general immunocompetence by assessing antibody response to SRBC,
      haemolytic complement level in the serum, in-vivo cell mediated immune (CMI)
      response to Concanavalin-A (Con-A) and a phagocytic index at 10-12 weeks of age.
      2. The naked neck gene did not seem to influence the antibody response to SRBC,
      CMI to Con-A or the phagocytic index. However, significantly higher haemolytic
      complement level in serum was observed in birds carrying a copy of the NA
      mutation as compared to the normally feathered birds. 3. Similar trends were
      observed for the frizzle gene.

PMID- 12003335
TI  - Within- and between-strain genetic variability in White Leghorn population
      detected through RAPD markers.
AB  - 1. Five White Leghorn (WLH) strains, namely G, H, I, J and C, differing in
      selection history, were screened for randomly amplified polymorphic DNA (RAPD)
      polymorphism using 50 random decamer primers. 2. Only 12 primers detected
      polymorphism between the strains. Out of 96 bands scored using these primers,
      only 21 (21.9%) were found to be polymorphic. 3. Strains differed considerably
      for within-population genetic similarity, estimated either by band sharing
      (WS=0.836 to 0.968) or band frequency (WF=0.820 to 0.969). 4. Between-strain
      genetic similarity estimates, based on band sharing (BS) as well as on band
      frequency (BF) ranged from 0.756 to 0.958 and from 0.830 to 0.996, respectively.
      Strains C and H were most closely related to each other, while J appeared to be
      more distant from other strains. 5. The between-strain genetic distance estimates
      also revealed similar trends. 6. A phylogenetic tree, derived using Nei's
      coefficient of similarity revealed similar relationships between the WLH strains.

PMID- 12003336
TI  - Use of molecular fingerprinting to assist the understanding of the epidemiology
      of Salmonella contamination within broiler production.
AB  - 1. We analysed Salmonella isolates by conventional sero- and phage-typing, as
      well as by molecular techniques within the broiler production chain in two
      integrated companies. The most prevalent serovars were selected for genetic
      fingerprinting. 2. Isolates were first screened by plasmid profiling;
      subsequently, the most common plasmid types within the prevalent zoonotic
      serovars (enteritidis and typhimurium) and S. agama were further characterised by
      PstI-SphI ribotyping, and XbaI pulsed field gel electrophoresis (PFGE). 3.
      Salmonella binza, S. kedougou, and S. 4,12:d:- were endemic in the feed mills
      over long periods of time, and a variety of plasmid types for each of the
      serovars were found in the premises. 4. A similar situation was found with S.
      binza and S. senftenberg within the hatchery in company B. The Salmonella
      serovars which were resident in those locations were also the ones most widely
      distributed throughout the broiler flocks. 5. Plasmid profiling was useful to
      subdivide clusters of isolates within serovars, but for each serovar a high
      percentage (36 to 79%) of the isolates tested fall within a prevalent plasmid
      type. 6. A more detailed genetic analysis of the isolates by a multiple typing
      approach allowed for further strain differentiation, and allowed some
      epidemiological conclusions to be drawn.

PMID- 12003337
TI  - Influence of dietary conjugated linoleic acid isomers on early inflammatory
      responses in male broiler chickens.
AB  - 1. The influence of dietary conjugated linoleic acid isomer (CLA, 0 and 10 g/kg)
      on the metabolic and physiological responses to immune stimulation induced by a
      single injection of Salmonella enteritidis lipopolysaccharide (LPS) or repeated
      injections of LPS and Sephadex G-50 was determined in male broiler chicks. 2. In
      experiment 1, 10-d-old chicks were fed on experimental diets for 14 d and half of
      the birds fed on each diet were injected intraperitoneally with LPS (1.5 mg/kg
      body weight). In experiment 2,7-d-old chicks were fed on experimental diets for
      18 d. Immune stimulation was started at 19 d old and continued for 5 d. Half of
      the birds fed on each diet were injected intraperitoneally with 0.25 mg/kg body
      weight of LPS at 19, 21 and 23 d of age, and with 250 mg/kg body weight of
      Sephadex at 20 and 22 d of age to stimulate the immune system. 3. In experiment
      1, giving CLA prevented an increase in blood heterophil to lymphocyte ratio 7 h
      after a single injection of LPS, and increases in plasma ceruloplasmin and alpha
      1 acid glycoprotein (AGP) 24 h after the injection, but not 7 h after the
      injection. CLA also prevented a decrease in food intake for 24 h after LPS
      injection. 4. In experiment 2, the CLA diet partially prevented reductions in
      body weight gain and weight gain to feed intake ratio caused by repeated
      injections of LPS and Sephadex. Feeding CLA prevented increases in plasma
      ceruloplasmin and AGP at 24 d of age caused by repeated injections of LPS and
      Sephadex, but not at 20 d of age. 5. These results suggest that feeding CLA
      alleviates some undesirable metabolic and physiological changes induced by
      immunological stimulation in male broiler chicks.

PMID- 12003338
TI  - Welfare assessment of broiler breeders that are food restricted after peak rate
      of lay.
AB  - 1. Broiler breeder females were reared on one of three growth curves (ad libitum,
      conventional or modified restriction) and given rations containing a high or low
      concentration of crude protein. After the peak rate of lay they were fed ad
      libitum or a decreasing quantity of food in response to declining egg production.
      The welfare of the birds was assessed by determining the changes in indices of
      welfare at 36, 48 and 60 weeks of age. 2. Body weight increased rapidly in
      restricted birds fed ad libitum post-peak and water intake declined. 3. Post-peak
      food restriction was associated with a decrease in resting and increased drinking
      and spot-pecking activities. Birds that were food restricted during rearing spent
      more time foraging and spot-pecking at 36 and 48 but not 60 weeks of age. 4.
      Immune function increased with age but was not affected by the experimental
      treatments. The heterophil-lymphocyte ratio in birds fed ad libitum during
      rearing was numerically lower at 36 and higher at 48 and 60 weeks of age compared
      with restricted birds. 5. There was no effect of treatment on plasma
      corticosterone concentration. Creatine kinase activity was high at 60 weeks in
      treatments that were characterised by poor reproductive status and the activities
      of other enzymes reflected differences in reproductive status and mortality. 6.
      There was no long-term welfare or production advantage from feeding low protein
      rations or more generous feeding during the rearing period compared with
      conventional food restriction programmes.

PMID- 12003339
TI  - Effects of feed enzymes on nutritive value of soyabean meal fed to broilers.
AB  - 1. The effects of two enzyme products on the nutritive value of soyabean meal
      (SBM) were investigated with the emphasis on changes in composition of non-starch
      polysaccharides (NSP) along the digestive tract. Enzyme A was a commercially
      available product containing mainly hemicellulase, pectinase, beta-glucanase and
      some protease activities and Enzyme B was an experimental product with mainly
      beta-galactanase activity. 2. Enzymes were added at the recommended dosage
      (normal) and at 5 times the recommended dosage (high) to a semi-purified diet
      based on maize with SBM as the sole protein source. 3. The enzymes had no effect
      on digesta viscosity in the jejunum or ileum. 4. Enzyme A at the high dosage
      significantly (P<0.05) improved AMEN, reduced excreta moisture content and
      improved ileal protein digestibility. The addition of the same enzyme at the
      recommended dosage had no effect on any of the above parameters. 5. Analysis of
      the monosaccharide composition revealed that Enzyme A tended to reduce the
      amounts of rhamnose and galactose in the soluble and insoluble NSP fractions in
      thejejunal and ileal digesta. The reduction was significant (P<0.05) when the
      same enzyme was added at the high dosage. 6. Enzyme B significantly (P<0.05)
      improved AMEN of the diet but not the growth or the feed conversion ratio (FCR)
      of the birds. Enzyme B at the high dosage significantly reduced (P<0.05) ileal
      protein digestibility. 7. Enzyme B significantly (P<0.05) increased the amount of
      free sugars in thejejunum and reduced (P<0.05) the concentration of soluble NSP
      in the ileum. 8. Analysis of the monosaccharide composition in the jejunal and
      ileal digesta showed that this enzyme was highly effective in releasing galactose
      from both the soluble and insoluble NSP fractions. 9. It is concluded that
      glycanases with galactanase and pectinase activities supplemented at appropriate
      dosages can improve the digestibility of the NSP in SBM and increase the
      metabolisable energy content of the diet containing high levels of SBM. 10.
      Furthermore, the addition of Enzyme B at the high dosage significantly (P<0.05)
      reduced protein digestibility without any measurable reduction in growth
      performance.

PMID- 12003340
TI  - Nutrient status of crop contents of rural scavenging local chickens in Tanzania.
AB  - 1. A total of 144 chickens purchased from peasants in Morogoro, Tanzania were
      slaughtered, their crops dissected and the contents analysed. The birds consisted
      of 48 chickens from each of three climatic zones (warm and wet, warm and dry,
      cool and wet). Seventy-two chickens were slaughtered in each season, that is
      short rainy and long rainy season. 2. Cereal grains, bran, green forages,
      insects/worms and kitchen food wastes were the main crop contents and their
      composition varied significantly with season and climate. 3. The overall mean
      chemical compositions (g/kg) of the crop contents were: 430.8 +/- 107.78 dry
      matter (DM), 104.4 +/- 43.47 crude protein (CP), 61.2 +/- 36.48 ether extract
      (EE), 58.2 +/- 26.29 crude fibre (CF), 125.4 +/- 58-27 ash, 6.3 +/- 5.19 calcium
      (Ca) and 3.6 +/- 2.41 phosphorus (P). 4. CP, EE, ash and P contents varied
      significantly (P<0.05) with season but contents of DM, CF and Ca were not
      significantly different. 5. CP content was significantly higher (P<0.05) in
      growers than in adults while the reverse was true for Ca content. Other variables
      did not differ significantly. 6. Significant differences (P<0.05) in chemical
      composition were observed among the zones in all parameters except for CP
      content. 7. The study showed that the chemical composition of feeds eaten by
      rural scavenging chickens was below the nutritional requirements and varied with
      season, climate and age of birds.

PMID- 12003341
TI  - The potential for the improvement of the nutritive value of soya-bean meal by
      different proteases in broiler chicks and broiler cockerels.
AB  - 1. The potential for improving the nutritive value of commercial solvent
      extracted, heat-treated soya-bean meal (SBM) by protease treatment was measured
      using growing broiler chicks and tube-fed broiler cockerels. 2. SBM was pre
      treated (50 degrees C for 2 h) with water alone; at alkaline pH (initial pH 8.25)
      with and without protease P1 (isolated from a Bacillus species) or at acid pH
      (initial pH 4.5) with and without protease P2 (isolated from an Aspergillus
      species) and incorporated into diets (290 g SBM/kg diet) for broiler chicks (20
      chicks/treatment). Only protease P2 treatment improved chick performance; from 7
      to 28 d of age, chicks fed on treated SBM had greater feed intakes and gained
      more weight than chicks fed on untreated SBM. Both proteases P1 and P2
      significantly reduced chick serum anti-soya antibodies while protease P2
      treatment increased apparent ileal nitrogen (N) digestibility and apparent N
      retention across the whole digestive tract. 3. Two tube-feeding experiments
      established that, of the treated SBMs used in experiment 1, only protease P2
      treatment improved apparent N digestibility and true metabolisable energy. Also
      it was shown that increasing the temperature at which treated SBM was dried to 60
      degrees C, compared with freeze-drying or drying at 50 degrees C reduced apparent
      N digestibility and true metabolisable energy of SBM with no significant
      interactions between enzyme treatment and drying temperature for both apparent N
      digestibility and TME. 4. It is concluded that, overall, the nutritional value of
      SBM assayed in a growth trial and by tube feeding was improved by treatment with
      protease P2 and not by treatment with protease P1.

PMID- 12003342
TI  - Analyses of degradation products from lipid and protein hydrolyses in the small
      intestine of broiler chickens fed on maize-based diets containing guar gum, or
      wheat-based diets.
AB  - 1. Three maize diets containing graded levels (0, 0.1, 0.3%) of guar gum and two
      wheat diets differing in their in vitro viscosities were fed to male broiler
      chickens (7 to 23 d) for measurements of growth performance and analyses of
      degradation products from lipid and protein hydrolyses in the small intestine of
      broiler chickens. Analyses of degradation products were conducted to define which
      step (hydrolysis or absorption) was most involved in the negative effects of the
      digesta viscosity on lipid and protein digestibilities. The experiment was also
      carried out to examine whether effects of wheats could be explained in terms of
      intestinal viscosity alone. 2. The intestinal viscosities with wheat diets were
      within the range of those observed with the three maize diets. The correlations
      between in vivo and in vitro viscosities were higher with real than with
      potential applied viscosity of diets, both in jejunum and ileum. 3. The mean
      gain:food ratio observed with wheat diets was lower (P<0.05) than with maize
      diets despite lower (P<0.05) mean intestinal viscosities in birds given the wheat
      than given the maize diets. This shows that factors different from intestinal
      viscosity were also involved in the negative effects of wheats. 4. Distributions
      of nitrogen compounds in digesta were characterised by low proportions of
      compounds with high molecular weight (>12,000). For all classes of nitrogen
      compounds, the contents measured in digesta dry matter did not differ between
      chickens fed with or without guar gum. 5. Distributions of lipid classes in both
      jejunum and ileum were characterised by a large proportion of free fatty acids
      (FFA) and very few triglycerides (TG). In the ileum, FFA and TG contents were
      both positively correlated with supernatant viscosity, but the slope for FFA
      content was 35 times higher than for TG. In these relationships, there was no
      difference between maize and wheat diets. 6. It is concluded that absorption was
      the main step involved in the lipid digestibility reduction due to intestinal
      viscosity. For proteins, the most important step (hydrolysis or absorption)
      involved in decreased digestibility due to intestinal viscosity was not clearly
      identified.

PMID- 12003343
TI  - Gizzerosine-induced histopathological lesions in broiler chicks.
AB  - 1. The aim of this study was to investigate pathomorphological changes in broiler
      chicks fed with different doses of gizzerosine, a substance produced during the
      heat treatments of fish meal. 2. The experiment was carried out in Ross broiler
      chicks which were divided into three groups: group A received 100% of non
      medicated commercial mash for broiler chicks. During an experimental 5-d period,
      50% of commercial mash was replaced with unheated fish meal (0.65 ppm
      gizzerosine) in group B and in group C with heated fish meal (1.15 ppm
      gizzerosine). Fourteen chicks from each group were killed every day. Samples of
      gastrointestinal and lymphoid organs, lung, pancreas, liver, brain and kidney
      tissue were sampled for histopathological analysis. Organs were embedded in
      paraffin and stained with hematoxylin-eosin stain and using periodic acid-Schiff
      reagent (PAS) and Sudan III (frozen sections). 3. Necropsy did not reveal notable
      differences between treated groups. There were no significant histopathological
      changes in immunocompetent organs nor in the lungs, the pancreas, the kidney or
      the brain. Sharply demarcated multiple vacuoles were observed in the myocardium
      in group C toward the end of the experiment. In group C, the prevalent changes in
      the gizzard and the proventriculus were slight to severe cuticle erosions and
      oedema of the lamina propria with or without multiple vacuoles, respectively,
      towards the end of the experiment. The most prominent changes toward the end of
      the experiment were dispersed cell vacuolisation in duodenal, jejunual, ileal and
      caecal lamina propria in group C. 4. In conclusion, it should be emphasised that
      extra-gizzard gizzerosine-induced lesions are probably not mediated by H2
      receptor stimulation, but could be a consequence of cellular hypoxia.

PMID- 12003344
TI  - Effects of low dietary protein and different allocations of food during rearing
      and restricted feeding after peak rate of lay on egg production, fertility and
      hatchability in female broiler breeders.
AB  - 1. A 3x2x2 factorial experiment was conducted with boiler breeder females to
      determine the effects of body weight gain (three levels) and conventional or
      lower crude protein concentrations in the rations during rearing, and restricted
      or ad libitum feeding after the peak rate of lay on egg production, fertility,
      hatchability, mortality and food consumption. 2. Compared with ad libitum
      feeding, conventional food restriction resulted in a decrease in average daily
      food consumption of 0.6 during rearing, 0.2 during early lay and an increase of
      0.4 after the peak rate of egg production. Mortality was decreased by more than
      half. 3. Restricted birds had higher total and settable egg production, fewer
      defective or damaged eggshells and higher fertility and hatchability than those
      fed ad libitum. The modified (more generous) rearing programme resulted in lower
      rates of egg production and higher rates of mortality compared with the
      conventional food restriction programme. 4. Low-protein rearing rations were
      associated with higher rates of food intake, higher mortalities and lower rates
      of egg production than the conventional protein rations. There were no
      differences in the fertility or hatchability of eggs between birds fed on the two
      concentrations of dietary crude protein. 5. Ad libitum feeding post-peak was
      associated with higher rates of mortality to 60 weeks of age. Post-peak feeding
      had little effect on the rate of lay or egg weight in conventionally restricted
      birds fed high protein rations or in birds fed ad libitum. Restricted feeding
      post-peak decreased the rate of lay and egg weight in birds on the modified
      restriction programme and in conventionally restricted birds fed on the low
      protein rations. There was no effect of post-peak feeding on fertility or
      hatchability of eggs. 6. The total numbers of saleable chicks per kg food
      consumed were 1.83, 1.72 and 0.52 for conventional, modified and ad libitum
      feeding during rearing; 1.56 and 1.15 for restricted and ad libitum feeding post
      peak: there were no differences associated with protein concentrations of rations
      fed during rearing.

PMID- 12003345
TI  - Biopterin analogues: novel nitric oxide synthase inhibitors with
      immunosuppressive action.
AB  - Tetrahydrobiopterin plays an essential role in nitric oxide synthase catalysis,
      not only as an allosteric modulator but also as a cofactor involved in electron
      flow through the enzyme. In absence of tetrahydrobiopterin, all isoforms of
      nitric oxide synthases are virtually inactive. The present review focuses on
      attempts to inhibit nitric oxide synthase by biopterin analogues, and what is
      known about the pharmacological effects of these compounds. While several
      biopterin analogues are capable of inhibiting nitric oxide synthases, the 4-amino
      analogue of tetrahydrobiopterin (4-amino tetrahydrobiopterin) is the compound of
      which pharmacological actions in animals have been described. 4-Amino
      tetrahydrobiopterin inhibits all three isoforms of nitric oxide synthases in
      micromolar concentrations. In cultured cells and in aortic strips, a surprising
      selectivity of inhibition of the inducible isoform of nitric oxide synthases has
      been observed. When applied intramuscularly, 4-amino tetrahydrobiopterin spreads
      throughout the body within minutes, and is cleared with a half life of about an
      hour. A single bolus dose applied intravenously in a rat model of septic shock,
      saved the animals from the lethal effects of endotoxin. When applied three times
      a day intramuscularly in a murine model of cardiac allograft rejection, 4-amino
      tetrahydrobiopterin prolongs allograft survival as efficiently as high-dose
      cyclosporin A treatment does. Thus, 4-amino tetrahydrobiopterin is an effective
      immunosuppressant. The mechanism of its action is currently under investigation.

PMID- 12003346
TI  - Disorders of tetrahydrobiopterin metabolism and their treatment.
AB  - Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine
      metabolism in liver and neurotransmitters biosynthesis in brain. BH4 is the
      essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids
      (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine
      triphosphate (GTP) catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl
      tetrahydropterin synthase, and sepiapterin reductase (SPR), and in aromatic amino
      acids hydoxylating system is regenerated by pterin-4a-carbinolamine dehydratase
      (PCD) and dihydropteridine reductase (DHPR). To date, 4 enzyme deficiencies
      (GTPCH, PTPS, DHPR, PCD) have been reported and they all follow an autosomal
      recessive mode of inheritance. The incidence of BH4 deficiency is at 1 in
      1,000,000, except that in Taiwanese (much higher than in Japanese and
      Caucasians). BH4 deficiency has been diagnosed in patients with
      hyperphenylalaninemia (HPA) by neonatal mass-screening based on BH4 oral loading
      tests, analysis of urinary or serum pteridines, and measurement of
      dihydropterindine reductase (DHPR) activity in blood from a Guthrie card. BH4
      deficiency without treatment causes combined symptoms of HPA and neurotransmitter
      (dopamine, norepinephrine, epinephrine, and serotonin) deficiency, such as red
      hair, psychomotor retardation, and progressive neurological deterioration.
      Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per
      day) or diet to control blood phenylalanine concentration and replacement therapy
      with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan), and
      supplements of folinic acid in DHPR deficiency.

PMID- 12003347
TI  - Tetrahydrobiopterin in nitric oxide synthesis: a novel biological role for
      pteridines.
AB  - Ever since the discovery that (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) is a
      cofactor of NOS, its function has been the object of intense research and
      occasional controversy. Only in the last couple of years a consensus has been
      reached on what constitutes the main role of BH4 in NO synthesis. In this review
      we aim to provide an outline of the various ways in which BH4 affects NOS
      catalysis. First we give a brief general description of the structure and
      catalytic mechanism of NOS, with special emphasis on those aspects of catalysis
      that are actively debated, and that directly or indirectly involve BH4. Foremost
      among those issues is uncoupled catalysis, i.e. the NOS-catalyzed oxidation of
      NADPH in the absence of substrate or pterin that does not result in NO
      production. We also shortly discuss the ongoing debate on whether NO is the
      actual reaction product of NOS catalysis, as well as the phenomenon of NO
      mediated autoinhibition. We describe the function of BH4 in aromatic amino acid
      hydroxylation, and discuss the allosteric and structural effects that BH4 exerts
      on NOS. Next we turn our attention to what is now becoming accepted as the
      central function of BH4: its capacity to act as a 1-electron donor during
      reductive activation of the oxyferrous complex of the heme. Finally, we
      illustrate how BH4 might transform the NOS dimer into an efficient S
      nitrosoglutathione synthase,and briefly touch on some more speculative aspects of
      the role of BH4 in NO synthesis.

PMID- 12003348
TI  - Tetrahydrobiopterin biosynthesis, utilization and pharmacological effects.
AB  - Tetrahydrobiopterin (H4-biopterin) is an essential cofactor of a set of enzymes
      that are of central metabolic importance, i.e. the hydroxylases of the three
      aromatic amino acids phenylalanine, tyrosine, and tryptophan, of ether lipid
      oxidase, and of the three nitric oxide synthase (NOS) isoenzymes. As a
      consequence, H4-biopterin plays a key role in a vast number of biological
      processes and pathological states associated with neurotransmitter formation,
      vasorelaxation, and immune response. In mammals, its biosynthesis is controlled
      by hormones, cytokines and certain immune stimuli. This review aims to summarize
      recent developments concerning regulation of H4-biopterin biosynthetic and
      regulatory enzymes and pharmacological effects of H4-biopterin in various
      conditions, e.g. endothelial dysfunction or apoptosis of neuronal cells. Also,
      approaches towards gene therapy of diseases like the different forms of
      phenylketonuria or of Parkinson's disease are reviewed. Additional emphasis is
      given to H4-biopterin biosynthesis and function in non-mammalian species such as
      fruit fly, zebra fish, fungi, slime molds, the bacterium Nocardia as well as to
      the parasitic protozoan genus of Leishmania that is not capable of pteridine
      biosynthesis but has evolved a sophisticated salvage network for scavenging
      various pteridine compounds, notably folate and biopterin.

PMID- 12003349
TI  - Neopterin as a marker for immune system activation.
AB  - Increased amounts of neopterin are produced by human monocytes/macrophages upon
      stimulation with the cytokine interferon-y. Therefore, measurement of neopterin
      concentrations in body fluids like serum, cerebrospinal fluid or urine provides
      information about activation of T helper cell 1 derived cellular immune
      activation. Increased neopterin production is found in infections by viruses
      including human immunodeficiency virus (HIV), infections by intracellular living
      bacteria and parasites, autoimmune diseases, malignant tumor diseases and in
      allograft rejection episodes. But also in neurological and in cardiovascular
      diseases cellular immune activation indicated by increased neopterin production,
      is found. Major diagnostic applications of neopterin measurements are, e.g.
      monitoring of allograft recipients to recognize immunological complications
      early. Neopterin production provides prognostic information in patients with
      malignant tumor diseases and in HIV-infected individuals, high levels being
      associated with poorer survival expectations. Neopterin measurements are also
      useful to monitor therapy in patients with autoimmune disorders and in
      individuals with HIV infection. Screening of neopterin concentrations in blood
      donations allows to detect acute infections in a non-specific way and improves
      safety of blood transfusions. As high neopterin production is associated with
      increased production of reactive oxygen species and with low serum concentrations
      of antioxidants like alpha-tocopherol, neopterin can also be regarded as a marker
      of reactive oxygen species formed by the activated cellular immune system.
      Therefore, by neopterin measurements not only the extent of cellular immune
      activation but also the extent of oxidative stress can be estimated.

PMID- 12003350
TI  - Immune monitoring in organ transplantation using neopterin.
AB  - Transplantation has become an established and successful therapy. Rejections and
      infections are the principal immune-related complications in the post-transplant
      course. A reliable and early diagnosis is necessary to prevent graft failure and
      patient morbidity. Despite the immunologic nature of these complications the
      diagnostic procedures still rely on functional tests and organ biopsies. Non
      invasive monitoring remains to be one of the major goals in transplant medicine.
      Neopterin is a sensitive marker of the cellular immune response. It reflects the
      activation of macrophages and can be easily measured in serum, plasma, urine or
      other body fluids. This review summarises studies on the diagnostic value of
      neopterin in transplant medicine. Based on these results key factors for immune
      monitoring in regard to neopterin are evaluated. In particular the unspecificity
      of diagnostic immune markers, the kinetics of the immune response, the importance
      of adjustment of neopterin to kidney function, and quantitative differences in
      immune pathways against viruses and allografts are discussed. Reflecting these
      points a concept to use neopterin for non-invasive immune monitoring in the
      clinical routine is presented. This approach calculates probabilities for
      specific post-transplant complications based on daily measurements of neopterin,
      a combination with the acute phase reactant amyloid A, and a modification of the
      likelihood ratio concept.

PMID- 12003351
TI  - Pteridine derivatives as modulators of oxidative stress.
AB  - Pteridine derivatives which have a widespread occurrence in nature have been
      investigated upon their interactions with free radicals and free radical mediated
      reactions utilizing a number of different experimental systems. Searching for
      biological functions, which are still unknown for the majority of pteridine
      compounds, the effect of pteridines in systems like luminol-induced
      chemiluminescence, enzyme activity, DNA photodamage, EPR experiments or radical
      induced injury--just to name a few--have been investigated. The general view
      during the initial phase of investigations on this special field was, that
      reduced pterins, i. e., tetra- as well as dihydropterins, generally act as
      radical scavengers, while aromatic pterins, if not inactive, exert radical
      promoting activity. Meanwhile the data available provide a more complex view:
      pteridines of all oxidation states have been shown to act anti- or
      prooxidatively, depending on the special conditions of the experiment. The reason
      is that reduced pterins, besides of being scavengers of free radicals, also are
      strongly reducing agents and therefore, in the presence of transition metal ions
      promote Fenton chemistry. Aromatic pterins have been described as inhibitors or
      substrates of enzymes involved--in vitro and in vivo--in free radical generation.
      Together with the unknown local concentrations of, e.g., neopterin and
      dihydroneopterin occurring in vivo, these reasons make it impossible to
      unequivocally predict a physiological net effect of pterins of different
      oxidation states concerning free radical mediated reactions in real biological
      systems.

PMID- 12003352
TI  - Physiology of folic acid in health and disease.
AB  - Folates are important cofactors in the transfer and utilization of one-carbon
      groups and play a key role in the remethylation of methionine thus providing
      essential methyl groups for numerous biological reactions. Furthermore, folates
      donate one-carbon units in the process of DNA-biosynthesis with implications for
      the regulation of gene expression, transcription, chromatine structure, genomic
      repair and genomic stability. As the role of folate deficiency in atherosclerotic
      cardiovascular disease, neurological and neuropsychiatric disorders, in
      congenital defects and carcinogenesis has become better understood, folate has
      been recognized as having great potential to prevent these many disorders through
      folate supplementation for the general population. Folate acts directly to
      produce antioxidant effects, interactions with enzyme endothelial NO synthase
      (eNOS) and effects on cofactor bioavailability of NO. Folate acts indirectly to
      lower homocysteine levels and insure optimal functioning of the methylation
      cycle. Folate metabolism provides an interesting example of gene-environmental
      interaction. A great part of the population, especially subgroups with higher
      demand, appears to have suboptimal folate intake, as determined through more
      sensitive parameters now widely determined. The available data strongly suggest
      that criteria for "folate deficiency" may have to be redefined.

PMID- 12003353
TI  - Hyperhomocysteinemia, pteridines and oxidative stress.
AB  - Tetrahydrofolate is an essential cofactor for the conversion of homocysteine to
      methionine, and hyperhomocysteinemia is considered as a risk factor for
      cardiovascular and cerebrovascular diseases. In subjects with
      hyperhomocysteinemia usually an inverse relationship exists to folic acid levels,
      and supplementation with folic acid is able to lower homocysteine concentrations.
      The pathogenesis of most if not all diseases which are accompanied with moderate
      hyperhomocysteinemia involves cellular immune activation and therefore in
      patients very often exists also a positive correlation between homocysteine
      concentrations and the degree of immune activation which is indicated, e.g. by
      increased neopterin concentrations. Since neopterin concentrations also serves as
      an estimate of oxidative stress merging from immune system activation, this
      association suggests that cellular immune activation and oxidative stress could
      be involved in the development of hyperhomocysteinemia. Because tetrahydrofolate
      is very susceptible to oxidation, an increased oxidative degradation of
      tetrahydrofolates may become relevant under oxidative stress conditions. In this
      way folate deficiency may develop despite normal dietary intake of the vitamin.
      In our patients, hyperhomocysteinemia is considered as an indirect consequence of
      hyperconsumption of antioxidant vitamins during prolonged states of immune
      activation.

PMID- 12003354
TI  - An interesting course after osteomyelitis of the proximal metaphysis of the femur
      in an infant: a case report.

PMID- 12003355
TI  - Traumatic spondylolisthesis of the axis: 42 cases.
AB  - Fourty-two patients (34 males and 8 female) with traumatic spondylolisthesis of
      the axis were studied in a retrospective review There were 20 stable and 22
      unstable fractures. The 22 unstable fractures were treated surgically: 16
      anterior interbody fusion (10 non-plated and 6 plated), 4 pedicle screw fixation
      for osteosynthesis of the fractured pedicles, and 2 posterior wire fixation for
      flexion and axial load injury. For all non-surgical cases, head halter tractions
      for 1 to 8 weeks was prescribed and a cervical orthosis was worn for an
      additional 6 to 18 weeks. The surgical cases underwent 5 to 7 days of
      preoperative and 1 to 4 weeks of post-operative head halter traction. In all
      cases pedicle fractures united after 13 weeks on average in group treated
      conservatively, 12 weeks (11 to 13 weeks) in the posterior wiring group, 8 weeks
      (7 to 9 weeks) in the group in which pedicle screws were used, and 11 weeks (9 to
      15 weeks) in the anterior fusion group (13 weeks in non-plated, and 8 weeks in
      plated). There were no differences in patterns of anterior fusion between those
      in the non-plated and plated groups. There were no non-unions of fractured
      pedicles and there was no late instability of the C2-C3 or neurological
      complications. In 2 cases in the posterior surgery group, there was mild nuchal
      discomfort and some rigidity for a short while postoperatively. Final outcomes
      were good in all cases.

PMID- 12003356
TI  - Effect of piriformis versus trochanteric starting point on fixation stability of
      short intramedullary reconstruction nails.
AB  - Recently, a new, shorter IM nail using two 6 mm reconstruction screws for
      proximal fixation was introduced in two versions for femoral insertion:
      piriformis fossa (FAN) and greater trochanter (TAN). These nails were compared
      experimentally for their fixation stability, proximal load transmission, and
      failure strength in an unstable intertrochanteric fracture model in cadaveric
      femurs. Vertical and axial loads were first applied to the intact femurs.
      Fractures were created, subsequent fixation applied, and the femurs underwent a
      series of both vertical and axial loading tests. There was no significant
      difference in strain readings between the nails for either axial loading or
      cyclical loading. There was no statistically significant difference between the
      loads to failure for the trochanteric nails and the standard antegrade nails. The
      average ultimate loadfor the FAN and TAN nails were 3010 N and 2830 N
      respectively. These two nails performed very similarly throughout our testing.

PMID- 12003357
TI  - The effect of screw type on the fixation of depressed fragments in tibial plateau
      fractures.
AB  - The ability of various screw types to stabilize depressed tibial plateau
      fractures was determined in a biomechanical study using a Sawbones model. Two
      sizes of both cancellous and cortical screws were evaluated for both supportfrom
      below and through the depressed fragment. As a general trend, cancellous bone
      screws provided a greater resistance to fragment displacement than cortical bone
      screws, and screws with a smaller thread diameter provided greater resistance to
      displacement than screws of the same thread type with a larger diameter. These
      results agree with the accepted standard that cancellous screws provide better
      fixation for tibial plateau fractures, but also are counterintuitive in that
      smaller screws provided greater fixation than larger screws of the same type.

PMID- 12003358
TI  - Patients' recollection of day case knee arthroscopy procedure.
AB  - A prospective study of 103 consecutive patients who underwent day case knee
      arthroscopy was performed. The purpose was to evaluate the information delivery
      system, patient comprehension, and issues of informed consent pertaining to day
      case arthroscopy procedures. There were 34 females and 69 males in the study
      group and their mean age was 38.6 years (range: 14.4 to 74.9 years). The
      diagnosis, procedure, and aftercare were explained to the patients in the
      outpatients clinic by a trained nurse and by the operating surgeon just prior to
      the operation. The nurse before the operation gave the patients an information
      booklet. Postoperatively the patients were informed about the findings and
      diagnosis prior to their discharge from the day care facility. Patients were
      requested to complete a questionnaire. Three weeks later they were given the same
      questionnaire, prior to consultation, in the outpatient clinic. These two forms
      were compared with the operative findings and diagnosis documented in the copy,
      of the questionnaire completed by the surgeon as well as the case notes. Most
      patients (38.8%; 40 patients) had no recollection; 3.9% (4 patients) had partial
      recollection at their consultation three weeks later; 19.4% (20 patients) found
      that the arthroscopic photograph was not helpful in making them understand the
      procedure; and 9.7% (10 patients) found the information booklet to be unhelpful.
      Further, 23.3% (24 patients) said that it would not help if the booklet were sent
      to them prior to the operation. The recollection rate was also correlated to
      their position on the operating list, to ascertain the effect of the anesthetic.
      There was a 65.9% (58 patients) recollection rate in those patients who were on
      the first half of the list and there was only a 33.33% recollection rate in those
      patients who were last or second to the last [p = 0.0225]. We recommend regular
      evaluation and improvement in the communication and information delivery system
      provided to patients.

PMID- 12003359
TI  - The effect of distal screw orientation on the intrinsic stability of a tibial
      intramedullary nail.
AB  - To compare the intrinsic stability of two distal interlocking screw orientations
      for tibial nailing of distal third tibial diaphyseal fractures without isthmal
      support, six Depuy (Warsaw, Indiana) tibial intramedullary nails were implanted
      in simulated distal tibiae. The constructs received both two parallel (medial to
      lateral) and two perpendicular (one medial to lateral, one anterior to posterior)
      distal interlocking screws in a random order Angular, translational, and
      torsional displacements of the nails were measured in response to 70 N proximal
      applications of anterior, posterior, medial, and lateral loads, and a 7.7 Newton
      meter torsional load. There were no differences in medial or lateral angulations
      between the screw orientations (average: 2.5 degrees, p > 0.8). Angulation in the
      sagittal plane (anterior and posterior) was slightly less for parallel screw
      fixation (1.6 degrees versus 2.4 degrees), but this was not statistically
      significant (p > 0.1). Rotational angulation was higher in the parallel (average:
      9.9 degrees) versus the perpendicular (average: 8.1 degrees) screw orientation,
      but these results were not statistically significant (p > 0.1). Pure translation
      did not occur in either the parallel or perpendicular screw orientations. These
      results indicate that fixation stability of these tibial intramedullary nails is
      not significantly influenced by distal interlocking screw orientation in response
      to sagittal, coronal, or rotational forces.

PMID- 12003360
TI  - Prevention of hip lag screw cut-out in osteoporotic patients: rationale and
      review of the literature.

PMID- 12003361
TI  - Hydatid disease of the left femur: a case report.
AB  - Osseous hydatid disease is a rare but serious condition. Treatment is difficult
      because of the progressive course of the bone involvement and generally admitted
      algorithm about osseous hydatid disease. We report a six-year follow-up of a case
      with involvement of the left femur, treated with an unconnected surgical method
      and albendazole. In this patient a 1 cm segment of the cortex between the
      trochanteric region to supracondylar area of the left femur was removed. The
      medullary cavity of the left femur was irrigated for 5 minutes with 20%
      hypersaline solution, and removed without causing any damage. The medullary
      cavity was curettaged meticulously and irrigated for 6 minutes with 0.9% saline
      solution. The bone defect was filled with bone cement. Albendazole was
      administered during the postoperative period. At the sixth year postoperatively,
      the patient was pain free. All serological tests were normal. Radiologic
      evaluation showed no evidence of disease recurrence. Meticulous preoperative
      planning, excision of all the cysts, and an effective regimen of chemotherapy
      will reduce recurrence. Bone scintigraphy is an important diagnostic method
      during the follow-up period.

PMID- 12003362
TI  - Bilateral carpal tunnel syndrome in a child on growth hormone replacement
      therapy: a case report.

PMID- 12003363
TI  - Tethered cord in a patient with multiple vertebral segmentation defects: a case
      report.
AB  - Short trunk dwarfism with multiple vertebral segmentation defects (MVSD)
      represents a heterogeneous group of disorders characterized by the presence of
      multiple vertebral and rib abnormalities. A two and one-half year-old female with
      the spondylothoracic dysostosisform of MVSD is presented. In addition to skeletal
      anomalies, a lumbar hemangioma, bilateral foot deformities, distal leg atrophy
      and weakness, and areflexia at the ankles were present. An underlying neuropathic
      process was suspected. Results of urodynamic studies were suggestive of a
      neurogenic bladder. Magnetic resonance imaging of the spine demonstrated a
      tethered spinal cord. Although various brain and spinal cord anomalies have been
      described in MVSD, this is the first reported case, to our knowledge, of a
      tethered spinal cord in a patient with MVSD. We recommend that the management of
      patients with MVSD include comprehensive neurological evaluation and monitoring
      with appropriate electrodiagnostic, urodynamic, and neuroimaging studies.

PMID- 12003364
TI  - Examining Type A behavior pattern to explain the relationship between job
      stressors and psychosocial outcomes.
AB  - Despite cautions against using a global measure of Type A behavior pattern
      (TABP), few studies have examined the TABP components of Achievement Striving
      (AS) and Impatience/Irritability (II). The authors examined these 2 components to
      assess whether they moderated the relationships between job stressors and
      psychosocial outcomes. Results based on 106 employees from a large Canadian
      organization supported the independence of the 2 TABP components. After
      controlling for the job stressors (i.e., overload, ambiguity, intrarole conflict,
      and lack of job control), II and AS accounted for additional variance in job
      satisfaction, perceived stress, and life satisfaction, although these components
      were uniquely related to different outcomes. Finally, AS and II moderated several
      of the stressor-psychosocial outcome relationships.

PMID- 12003365
TI  - Supportive colleague, unsupportive supervisor: the role of provider-specific
      constellations of social support at work in the development of low back pain.
AB  - In a 5-year longitudinal study, social support was investigated as a predictor of
      low back pain (LBP) in 46 initially asymptomatic individuals. Distinguishing
      between colleagues in general and the colleague one feels closest to, the authors
      analyzed constellations of support from supervisor (which had positive effects)
      and closest colleague (which had detrimental effects). Configural frequency
      analysis yielded a type characterized by high support from one's closest
      colleague and low support from one's supervisor at Time 1 and more LBP and
      disability at Time 2. Controlling for negative affectivity did not change
      findings. Results are interpreted in terms of being dependent on that one source
      of support in an unsupportive environment, which creates feelings of dependence,
      incompetence, and reciprocity obligations.

PMID- 12003366
TI  - Workplace harassment, services utilization, and drinking outcomes.
AB  - Given the negative outcomes associated with sexual harassment (SH) and
      generalized nonsexual workplace harassment (GWH), this study examines the
      relationship between SH and GWH and help-seeking behavior in a sample of 2,038
      university employees. Employees who experienced SH or GWH were more likely to
      report having sought mental health or health services to deal with workplace
      issues, compared with those who did not experience SH or GWH, controlling for job
      stress and prior services use. Women experiencing GWH were more likely to use
      services than men, but the same was not true for SH. Men experiencing SH who
      sought services exhibited higher levels of some alcohol outcomes, contrary to
      expectations. Implications for workplace interventions and for service providers
      are discussed.

PMID- 12003367
TI  - Age, smoking, and negative affectivity as predictors of sleep patterns among
      shiftworkers in two environments.
AB  - Although adaptation to shiftwork has been widely studied, little is known about
      how individual and environmental factors combine to influence sleep among
      shiftworkers. This study examined age, smoking, and negative affectivity (NA) as
      predictors of sleep duration and quality for 3 work phases (day shifts, DS; night
      shifts, NS; and leave periods, LP). Data were collected from personnel working 12
      hr shifts, onshore (n = 330) or offshore (n = 456). Individual factors predicted
      patterns of sleep measures across the DS, NS, and LP phases onshore, but not
      offshore; onshore, work phase interacted with smoking and with age to predict
      sleep duration and with NA to predict sleep quality. The role of the offshore
      environment in shiftwork adaptation is discussed.

PMID- 12003368
TI  - Sexual assault and other types of sexual harassment by workplace personnel: a
      comparison of antecedents and consequences.
AB  - Although sexual assault by workplace personnel is widely viewed as a type of
      sexual harassment, little is known about whether these overlapping constructs may
      possess some unique characteristics. This article compares the theoretical
      antecedents and consequences of sexual assault by workplace personnel and other
      types of sexual harassment among 22,372 women employed in the U.S. military. Path
      analysis revealed that low sociocultural and organizational power are associated
      with an increased likelihood of both types of victimization. Organizational
      climate and job gender context are directly associated with sexual harassment but
      are only indirectly associated with sexual assault by workplace personnel. Both
      types of victimization are associated with a variety of negative outcomes, but
      the pattern of negative consequences differs.

PMID- 12003369
TI  - Work-family conflict, perceived organizational support, and organizational
      commitment among employed mothers.
AB  - This study investigated the impact of work interfering with family (WIF) and
      family interfering with work (FIW) on women's organizational commitment and
      examined both the direct and moderating effects of their perceived organizational
      support. Participants were 143 professional employed mothers with at least 1
      preschool-age child. The study found that WIF was positively related to
      continuance organizational commitment but unrelated to affective commitment, and
      FIW was not related to either form of organizational commitment. Results also
      indicated that perceived organizational support exhibited a main effect on both
      types of commitment.

PMID- 12003370
TI  - A new century of antirheumatic therapy.

PMID- 12003371
TI  - The pathogenesis of rheumatoid arthritis: a guide to therapy.
AB  - The cause of rheumatoid arthritis (RA) is unknown; however, extensive research
      has yielded great insight into its pathogenesis. Lymphocytes play a significant
      role, but a lesser role in the perpetuation of late disease. The rheumatoid
      synovium is composed primarily of fibroblasts and monocytes that produce
      inflammatory cytokines, of which interleukin-1 and tumor necrosis factor are of
      key importance. Potential regulatory mechanisms balancing the effects of these
      cytokines are inadequate to prevent joint damage and subsequent disability. These
      cytokines seem responsible for stimulating destructive processes in the joint via
      induction of prostaglandins, angiogenesis, chemokines, adhesion molecules,
      osteoclastogenesis, and matrix metalloproteinases. This review discusses recent
      research findings in the immunopathogenesis of RA with respect to potential
      targets for therapy.

PMID- 12003372
TI  - Cox-2 inhibitors: today and tomorrow.
AB  - The elucidation of inducible cyclooxygenase (Cox-2) dependent inflammatory
      pathways led to the development of specific Cox-2 inhibitors, the coxibs. These
      agents include the currently available celecoxib and rofecoxib and such second
      generation agents as parecoxib, valdecoxib, and etoricoxib. The therapeutic
      advantage of coxibs is founded primarily in their lack of significant
      gastrointestinal (GI) side effects. Clinical trials have demonstrated the
      efficacy of coxibs to be completely comparable with traditional nonsteroidal anti
      inflammatory drugs (NSAIDs), and pharmacoeconomics suggest favorable cost/benefit
      ratios with these agents compared with traditional NSAIDs, related to their
      reduced GI complication profiles and lower indirect costs associated with
      disability. Although several clinical questions remain (eg, use with low-dose
      aspirin, risk of thrombosis, myocardial infarction, edema, and hypertension), the
      emergence and clinical utility of coxibs is likely to continue on the basis of
      their efficacy and relative GI safety advantage. Although newer, more specific
      Cox-2 inhibitors may alter the choice, it is likely that this class of anti
      inflammatories will become (if they have not already) the drugs of first choice
      in the treatment of acute pain, chronic pain, and most rheumatic conditions in
      the 21st century. In addition to the treatment of rheumatic conditions, it is
      possible that coxibs will also be of clinical utility in protection against
      malignant transformation and Alzheimer disease.

PMID- 12003373
TI  - Leflunomide for the treatment of rheumatoid arthritis and autoimmunity.
AB  - Leflunomide, a new oral immunomodulatory agent, is effective for the treatment of
      rheumatoid arthritis. Its mechanism of action in suppressing inflammation is
      based in its inhibition of dihydroorotate dehydrogenase, an enzyme responsible
      for de novo synthesis of pyrimidine containing ribonucleotides. It is the first
      disease-modifying antirheumatic drug approved for treatment of rheumatoid
      arthritis with an indication for retardation of joint damage by radiography. Side
      effects are generally mild and include diarrhea, rashes, reversible alopecia, and
      elevation of hepatic transaminases. Despite the concern about hepatotoxicity,
      combination use with methotrexate in treating patients with rheumatoid arthritis
      has been shown to be safe. Other autoimmune diseases in which leflunomide has
      been used successfully include Felty syndrome, vasculitis, Sjogren syndrome,
      Wegener granulomatosis, and bullous pemphigoid.

PMID- 12003374
TI  - Mycophenolate mofetil: selective T cell inhibition.
AB  - Mycphenolate mofetil is a suppressor of T cell proliferation and adhesion. Its
      primary mode of action is inhibition of inosine monophosphate dehydrogenase, a
      purine salvage pathway required by T lymphocytes. Although the role of T cells in
      rheumatoid arthritis (RA) has been controversial, a preliminary report of
      mycophenolate mofetil's successful use in RA patients clearly suggests that its
      efficacious properties need further investigation. Its favorable risk/benefit
      ratio, a broad clinical experience in kidney transplantation, and its recent
      extension to other rheumatic diseases suggests that this new antirheumatic agent
      has significant therapeutic potential for suppression of synovial inflammation.

PMID- 12003375
TI  - Biological modifier therapy for the treatment of rheumatoid arthritis.
AB  - The recent elucidation of pathogenic processes involving tumor necrosis factor
      alpha and interleukin-1beta in the pathogenesis and persistence of rheumatoid
      arthritis led to the development of biological modifier agents that have had
      significant impact on disease severity and progression. These agents--etanercept,
      infliximab, and anakinra--produce a dramatic reduction in RA disease activity
      with relatively low toxicity compared with currently available disease-modifying
      antirheumatic drugs. The main prohibition to their broader utilization is cost.
      The success of these agents underscores the investigative approaches to the
      pathogenesis of RA and the appropriate design of pharmaceutical agents to target
      specific proinflammatory molecules.

PMID- 12003376
TI  - Higher serum leptin level in women than in men with type 1 diabetes.
AB  - Leptin is the protein product of the obese (ob) gene, a lipostatic hormone that
      contributes to body weight regulation through suppressing appetite and/or
      stimulating energy expenditure in humans and/or rodents. In humans, serum leptin
      concentrations are increased in relation to increased body fat content. Studies
      have shown a higher leptin level in women compared with men. However, the gender
      influence on serum leptin concentrations has never been evaluated in patients
      with type 1 diabetes. In this study, serum leptin levels and percentage body fat
      mass were measured in men and women with type 1 diabetes. Fasting serum leptin
      levels were higher in women (16.7 + 11.6 ng/mL) than in men (3.0 +/- 1.5 ng/mL; P
      < 0.05) and were independent of exogenous insulin intake and of glucose control.
      Percentage body fat and fat mass were significant determinants of leptin
      concentration, whereas age and duration of diabetes were not related to leptin
      concentration. Subgroups of men (n = 12) and women (n = 11) with total body fat
      between 20 and 30% were compared. Leptin levels were also higher in women
      compared with men (13.5 +/- 8.3 ng/mL versus 3.2 +/- 1.7 ng/mL; P < 0.05,
      respectively). In conclusion, our findings indicate that gender is an important
      determinant of serum leptin concentration in type 1 diabetics, this gender
      difference is partly explained by body fat distribution and that type 1 diabetic
      women may be more resistant than type 1 diabetic men to leptin's alleged
      lipostatic actions.

PMID- 12003377
TI  - Parathyroid hormone suppression by intravenous calcitriol: role of phosphate,
      calcium, race and diabetes.
AB  - BACKGROUND: Parathyroid hormone (PTH) suppression in patients with end-stage
      renal disease (ESRD) undergoing maintenance hemodialysis is achieved largely by
      the use of intravenous calcitriol. Aspects of the utility and efficacy of this
      therapy remain controversial. It is debated whether oral versus intravenous
      therapy is more effective. Most existing studies examine the effect of calcitriol
      in isolation, without adjusting for other factors that might influence PTH
      levels. Thus, the simultaneous role of factors such as dosing, control of serum
      calcium and phosphorus, and demographic variables such as age, sex, race, and
      duration of ESRD is not well understood. METHODS: We examined the relationship
      between the administration of calcitriol and PTH suppression in a cohort of
      hemodialysis patients at a large urban dialysis facility over a period of 30
      months. Hemodialysis patients (n = 155) who received at least 3 months of
      treatment in this facility were included. RESULTS: Using a time sensitive
      multiple linear regression modeling technique, we found that second and
      subsequent PTH levels were positively correlated with black race (P < 0.0001) and
      serum phosphate (P < 0.03) and strongly negatively correlated with serum calcium
      (P< 0.0001) and diabetes (P< 0.0039). Drug dose (in micrograms per kilogram per
      month) was weakly negatively correlated (P < 0.04). Unlike previous studies, we
      adjusted for the simultaneous confounding influence of demographic and laboratory
      variables, as well as for drug dose normalized for body weight. CONCLUSIONS: This
      analysis suggests that calcitriol therapy in hemodialysis patients is adversely
      affected by higher phosphate levels and needs to account for such patient
      characteristics as race and diabetes and such laboratory variables as calcium and
      phosphate control. Finally, as has been recently suggested by others, the
      patient's race may require us to aim for different PTH target levels with
      therapy.

PMID- 12003378
TI  - Smallpox and the Native American.
AB  - With the arrival of Europeans in the Western Hemisphere, Native American
      populations were exposed to new infectious diseases, diseases for which they
      lacked immunity. These communicable diseases, including smallpox and measles,
      devastated entire native populations. In this article, we focus on the effect of
      smallpox on the Native Americans from the 15th through the 19th centuries. Among
      the "new" infectious diseases brought by the Europeans, smallpox was one of the
      most feared because of the high mortality rates in infected Native Americans.
      This fear may have been well-founded, because the Native Americans were victims
      of what was probably one of the earliest episodes of biological warfare.
      Fortunately, they were also major beneficiaries of early vaccination programs.
      Thus, the arrival of smallpox and the decline of the Native American populations
      are inexorably linked, as the history summarized here illustrates.

PMID- 12003379
TI  - Anomalous left coronary artery arising from the right sinus of valsalva in a man
      with unstable angina pectoris and right coronary artery stenosis.
AB  - A 54-year-old man developed unstable angina pectoris and was found to have both
      an anomalous left coronary artery, which arose from the right sinus of Valsalva
      and followed an intramyocardial (septal) course, and severe atherosclerotic
      stenosis of the mid-right coronary artery. Stress perfusion imaging showed
      ischemia in the distribution of the right coronary artery, leading to successful
      percutaneous transluminal balloon angioplasty of the right coronary artery rather
      than surgical correction of the congenital anomaly.

PMID- 12003380
TI  - Changes in serum albumin during treatment of chronic hepatitis B with lamivudine:
      effects of response and emergence of drug resistance.
AB  - OBJECTIVES: In chronic hepatitis B patients treated with lamivudine, the
      incidence of drug resistance increases with the duration of therapy. The effect
      of drug resistance on hepatic synthetic function is not well defined. The aim of
      the present study was to assess the effect of lamivudine therapy on hepatic
      synthetic function in patients with moderately severe chronic hepatitis B and,
      particularly, to determine the effect of drug resistance. METHODS: Hepatic
      synthetic function was assessed using serial measurements of serum albumin in 38
      patients (26 with cirrhosis) in an open-label treatment program. RESULTS: An
      initial antiviral response (hepatitis B virus [HBV] DNA undetectable by
      hybridization assay) occurred in all patients, and nine of 22 (41%) hepatitis B e
      antigen-positive cases underwent hepatitis B e antigen seroconversion. Among 29
      patients with undetectable serum HBV DNA at the end of observation, the mean
      serum albumin concentration rose from 39.9 +/- 0.7 to 43.2 +/- 0.6 g/L,
      corresponding to a yearly increase of 1.85 g/L (p < 0.001). This was largely
      attributable to an increase among cirrhotic patients. Nine patients (24%)
      developed resistance to lamivudine, all after 12 months of treatment. Among them,
      the mean serum albumin concentration had increased from 39.6 +/- 1.2 to 42.9 +/-
      0.8 g/L before resistance emerged, but then decreased to 39.3 +/- 1.7 g/L (p =
      0.01) at the time of reappearance of HBV DNA. CONCLUSION: Suppression of viral
      replication by lamivudine improves hepatic synthetic function in chronic
      hepatitis B patients, but emergence of drug resistance is associated with a rapid
      decline in serum albumin, at least to pretreatment levels.

PMID- 12003381
TI  - A randomized controlled trial of cyanoacrylate versus alcohol injection in
      patients with isolated fundic varices.
AB  - OBJECTIVE: Treatment of bleeding gastric varices (GVs) is still controversial,
      mainly because of anecdotal studies or inclusion of patients with GVs located at
      different sites that have variable incidences of bleeding. A prospective study
      was undertaken to compare the efficacy and safety of GV sclerotherapy using
      alcohol and GV obturation using cyanoacrylate glue. METHODS: Thirty-seven
      consecutive patients with portal hypertension and endoscopic evidence of isolated
      GVs, 17 presenting with histories of active bleeding, were randomized to receive
      endoscopic intervention either with alcohol (n = 17) or with cyanoacrylate glue
      (n = 20) injection. Variceal obliteration, rebleeding, or death was the endpoint.
      RESULTS: The glue was significantly more effective in achieving variceal
      obliteration than alcohol (100% vs 44%, p < 0.05). Furthermore, this could be
      achieved in a significantly shorter period (2.0 +/- 1.6 vs 4.7 +/- 3.2 wk, p <
      0.05) and with a smaller volume of the agent. Cyanoacrylate glue injection could
      achieve arrest of acute GV bleeding more often than alcohol (89% vs 62%), and the
      need for rescue surgery was less; the difference was, however, not significant.
      Six patients died from uncontrolled GV bleeding, four being in the alcohol group.
      During a mean follow-up of 15.4 +/- 3.7 months there was no recurrence of GVs in
      either group. CONCLUSIONS: Our results show that cyanoacrylate is more effective
      and achieves GV obliteration faster than injection sclerotherapy with alcohol. It
      also appears to be more useful in controlling acute GV bleeding, with less of a
      need for rescue surgery.

PMID- 12003382
TI  - HFE gene mutations in alcoholic and virus-related cirrhotic patients with
      hepatocellular carcinoma.
AB  - OBJECTIVE: The increased risk of developing hepatocellular carcinoma in
      hereditary hemochromatosis has been associated with cirrhosis and hepatic iron
      overload. The aim of this study was to investigate the association between HFE
      gene mutations (C282Y, H63D) and hepatocellular carcinoma in patients with
      alcoholic and virus-related cirrhosis. METHODS: Serum markers of iron status and
      HFE mutations were determined in 179 patients with alcoholic cirrhosis and 98
      patients with hepatitis B and/or hepatitis C virus-related cirrhosis. A total of
      43 patients with alcoholic cirrhosis and 34 patients with virus-related cirrhosis
      had hepatocellular carcinoma. The control group consisted of 159 healthy bone
      marrow donors. RESULTS: No differences were found in the frequencies of mutations
      among patients with alcoholic cirrhosis, those with virus-related cirrhosis, and
      the control subjects. However, nine (20.9%) of the 43 patients with alcoholic
      cirrhosis and hepatocellular carcinoma were heterozygous for the C282Y mutation,
      compared with six (4.4%) of the 136 patients without tumor (p = 0.002). This
      difference was not found in patients with virus-related cirrhosis, with or
      without hepatocellular carcinoma, or the H63D mutation. The transferrin
      saturation was the only serum iron marker the value of which was significantly
      higher among C282Y heterozygotes with alcoholic cirrhosis compared to those
      without mutation. CONCLUSIONS: The high frequency of heterozygosity for the C282Y
      mutation in patients with alcoholic cirrhosis plus hepatocellular carcinoma
      suggests that the presence of this mutation could be associated with an increased
      risk of developing hepatocellular carcinoma in these patients.

PMID- 12003383
TI  - Telomerase activity in pancreatic endocrine tumors.
AB  - OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and
      predictors of survival are lacking. PETs can be difficult to distinguish
      histologically from aggressive pancreatic neoplasms such as acinar cell
      carcinoma. Telomerase is a ribonuclear protein that maintains the length of the
      telomere and induces cell immortality. Telomerase is present in 95% of pancreatic
      adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to
      determine telomerase activity in PETs and investigate its potential role as a
      prognostic indicator. METHODS: Telomerase detection using the telomeric repeat
      amplification protocol was performed on frozen surgical archived pancreatic
      endocrine tissue from 30 patients with PETs identified by light microscopy
      (hematoxylin-eosin stain). All results were confirmed with internal controls. A
      patient's survival was measured from the time of surgery. Acinar cell
      differentiation (presence of zymogen granules) was determined by electron
      microscopy. Follow-up data were acquired via telephone interview, medical record
      review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light
      microscopy were telomerase positive: three were considered nonfunctional, and two
      of these three patients had extrapancreatic disease. All three telomerase
      positive cases were reclassified as either acinar cell carcinoma (two cases) or
      mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age =
      63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr +/- 0.5
      SD). The remaining PETs were telomerase negative: 13 insulinomas, four
      nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one
      carcinoidlike PET, and five PETs from three patients with multiple endocrine
      neoplasm syndrome type I and two patients with von Hippel-Lindau syndrome.
      Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had
      extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these
      12 patients were significantly longer than for patients with telomerase-positive
      acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival
      of all telomerase-negative PETs (n = 27) was significantly longer than that of
      the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p
      = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell
      carcinomas that histologically resemble PETs, which accounts for the poor
      prognosis demonstrated in these patients. The absence of telomerase activity in
      most PETs may be responsible for their indolent clinical course. Telomerase may
      identify potentially progressive tumors, such as acinar cell carcinoma, and may
      be useful in selecting patients for more aggressive treatment.

PMID- 12003385
TI  - Inhaler.

PMID- 12003384
TI  - Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal
      cancer.
AB  - OBJECTIVE: We aimed to investigate the associations of cyclooxygenase-2 (COX-2)
      with pathological features and survival in patients with colorectal cancer.
      METHODS: The expression of COX-2 was examined by immunohistochemistry in 112
      primary colorectal cancers, with 64 samples from the corresponding normal mucosa
      and 16 metastases in the regional lymph nodes of patients with colorectal cancer.
      The associations of COX-2 expression with clinicopathological features, including
      survival, were analyzed. RESULTS: The frequency and intensity of COX-2 staining
      were remarkably increased from the normal samples (17%) to the primary tumors
      (72%) and to the metastases (100%). Expressions of COX-2 were 25%, 74%, 78%, and
      67% in Dukes' A, B, C, and D tumors, respectively (p = 0.005), and positively
      related to proliferative activity (p = 0.003). COX-2 expressions were 80% in
      colonic tumors and 60% in rectal tumors (p = 0.03). The expression of COX-2 was
      positively related to the better differentiated tumors in the colon (p = 0.04).
      We were unable to find any relationship of COX-2 with patient age, sex, tumor
      growth pattern, apoptosis, and patient survival (p > 0.05). CONCLUSION: We found
      that the expression of COX-2 was upregulated from normal cells to primary tumors
      and to metastases, and related to proliferative activity, tumor location, Dukes'
      stage, and differentiation. These results further support the evidence that COX-2
      may be involved in tumorigenesis and development of colorectal cancer.

PMID- 12003386
TI  - Ureteropelvic junction obstruction: an overlooked cause of cyclic vomiting.
AB  - Cyclic vomiting syndrome is an unusual cause of recurrent episodes of repetitive
      vomiting, particularly in children. Although in only a minority of cases can an
      underlying cause be found, each patient deserves a thorough evaluation for
      treatable conditions. We present four cases of cyclic vomiting syndrome caused by
      ureteropelvic obstruction. Surgical correction was followed by resolution of
      symptoms in all four patients.

PMID- 12003387
TI  - Heterotopic pancreas presenting as dysphagia.
AB  - Heterotopic pancreatic tissue, also known as a pancreatic rest, is an uncommon
      congenital anomaly defined as extrapancreatic tissue located far from the
      pancreas and without connection via vascular or anatomical means to it. Such
      tissue may occur throughout the GI tract but has a propensity to affect the
      stomach and the proximal small intestine. The majority of patients with
      pancreatic heterotopia are asymptomatic, but when symptoms occur, they can
      present in a variety of ways. We report a case of a patient whose pancreatic rest
      presented primarily as dysphagia for solid food and in whom endoscopic ultrasound
      was used to further define the lesion. There have been only two cases reported of
      a pancreatic rest causing symptoms of dysphagia. A review of the literature on
      pancreatic heterotopia as well as the use of endoscopic ultrasound as an aid in
      evaluation is included.

PMID- 12003388
TI  - A patient with autoimmune hepatitis type I, Addison's disease, atrophic
      thyroiditis, atrophic gastritis, exocrine pancreatic insufficiency, and
      heterozygous alpha1-antitrypsin deficiency.
AB  - This report describes a 60-yr-old white male presenting with decompensated liver
      cirrhosis. He had a history of Addison's disease for 36 yr, primary
      hypothyroidism for 5 yr, and moderate alcohol consumption. His laboratory studies
      and a liver biopsy supported the diagnosis of autoimmune hepatitis. Furthermore,
      he was found to be heterozygous for the piZ allele of the alpha1-antitrypsin gene
      with normal serum alpha1-antitrypsin levels and absence of pulmonary affection.
      Mucosal biopsies revealed moderately severe atrophic gastritis; however, signs of
      pernicious anemia were missing. An association of autoimmune hepatitis with
      endocrine disorders and atrophic gastritis has been described. Long term
      hydrocortisone therapy for his adrenal insufficiency may have prevented a faster
      course of the liver disease, whereas the heterozygous alpha1-antitrypsin
      deficiency and moderate alcohol consumption constituted additional risk factors
      ultimately leading to the development of cirrhosis.

PMID- 12003389
TI  - MARS dialysis in the state of chronic rejection in a liver transplant recipient.

PMID- 12003390
TI  - GI metastases from melanoma: a case report.

PMID- 12003391
TI  - Rofecoxib and cytomegalovirus in acute flare-up of ulcerative colitis:
      coprecipitants or coincidence?

PMID- 12003392
TI  - A resected case of adenoneurofibroma of the colon: is it a new entity of the
      colonic tumor?

PMID- 12003393
TI  - Intravenous access during routine conscious sedated endoscopy.

PMID- 12003394
TI  - H. pylori-infected gastroesophageal reflux disease patients harbor less virulent
      strains.

PMID- 12003395
TI  - Comment on the comment of Dr. Daniel Present.

PMID- 12003396
TI  - Suicide as an outcome in patients with inflammatory bowel disease.

PMID- 12003397
TI  - Macroamylasemia in celiac disease: a novel observation, but what does it mean?

PMID- 12003398
TI  - Hemothorax after percutaneous liver biopsy: an unusual complication.

PMID- 12003399
TI  - High-resolution magnification chromoendoscopy: common problems encountered in
      "pit pattern" interpretation and correct classification of flat colorectal
      lesions.

PMID- 12003400
TI  - Growth hormone plasma levels in nonalcoholic fatty liver disease.

PMID- 12003401
TI  - Ticlopidine-induced cholestatic hepatitis successfully treated with
      corticosteroids.

PMID- 12003402
TI  - Oral administration of ketotifen in a patient with eosinophilic colitis and
      severe osteoporosis.

PMID- 12003403
TI  - Acute severe steatohepatitis related to prednisolone therapy.

PMID- 12003404
TI  - Is bezafibrate histologically effective for primary biliary cirrhosis?

PMID- 12003405
TI  - Acute pancreatitis associated with rofecoxib.

PMID- 12003406
TI  - Physician compliance with colon cancer screening.

PMID- 12003407
TI  - Gallbladder carcinoma secondary to repetitive hepatic arterial chemoembolization.

PMID- 12003408
TI  - Using COX-2 inhibitors in IBD: anti-inflammatories inflame a controversy.

PMID- 12003409
TI  - Treatment of Crohn's disease with budesonide: this rose still has thorns!

PMID- 12003410
TI  - Vitamin K replacement in osteoporosis associated with cirrhosis: another reason
      to "eat your vegetables"?

PMID- 12003411
TI  - Iron and the response to treatment of hepatitis C.

PMID- 12003412
TI  - Microscopic colitis: a review.
AB  - Microscopic colitis is a relatively common cause of chronic watery diarrhea,
      often accompanied by abdominal pain and weight loss. The colonic mucosa appears
      normal grossly, and the diagnosis is made when there is an intraepithelial
      lymphocytosis and a mixed inflammatory infiltrate in the lamina propria. The two
      main subtypes, collagenous and lymphocytic colitis, are similar clinically and
      histologically, distinguished by the presence or absence of a thickened
      subepithelial collagen band. Many potential pathophysiological mechanisms have
      been described, although none have been conclusively proved. There is a paucity
      of randomized treatment trials in these patients, although a rational approach to
      therapy often leads to satisfactory control of symptoms.

PMID- 12003413
TI  - Corticosteroids in Crohn's disease.
AB  - Crohn's disease is a lifelong illness characterized by chronic recurrent flares.
      The precise etiology of Crohn's disease is unknown. However, it appears to
      involve an enhanced systemic immune response and intensified local intestinal
      mucosal inflammatory activity, mediated through various inflammatory cells and an
      array of proinflammatory cytokines. Corticosteroids have been the mainstay of
      treatment of Crohn's disease. The controlled trials of the National Cooperative
      Crohn's Disease Study and the European Cooperative Crohn's Disease Study
      established that corticosteroids were effective for the induction of remission in
      Crohn's disease for the duration of the studies (6-17 wk). However,
      corticosteroids have not been shown to have an impact on the maintenance of long
      term remission in patients with Crohn's disease. In addition, they are associated
      with a high potential for dependence and serious toxic side effects. Alternative
      classes of medical therapy for Crohn's disease, including modified
      corticosteroids and a group of new biological therapies, have proven to be
      efficacious in the management of active and/or quiescent Crohn's disease.

PMID- 12003414
TI  - Chronic abdominal wall pain: a frequently overlooked problem. Practical approach
      to diagnosis and management.
AB  - Chronic abdominal wall pain is frequently misdiagnosed as arising from a visceral
      source, often resulting in inappropriate diagnostic testing, unsatisfactory
      treatment, and considerable cost. Its prevalence in general medical practice is
      unknown, although it may account for about 10% of patients with chronic
      idiopathic abdominal pain seen in gastroenterological practices. The most common
      cause appears to be entrapment of an anterior cutaneous branch of one or more
      thoracic intercostal nerves; myofascial pain and radiculopathy are less frequent.
      Sharply localized pain and superficial tenderness are suggestive of abdominal
      wall origin. Carnett's test (accentuated localized tenderness with abdominal wall
      tensing) is a helpful diagnostic sign, especially when incorporated with other
      findings. Early exclusion of a parietal source should increase diagnostic
      accuracy when evaluating patients with chronic abdominal pain. Reassurance of
      patients by the correct diagnosis and avoidance of precipitating causes is often
      sufficient treatment. However, accurately placed anesthetic/corticosteroid
      injections give substantial pain relief to more than 75% of patients, often for
      prolonged periods, and may be confirmatory for the source of the complaint. The
      probability of missing visceral disease is small (probably less than 7%) with
      strict adherence to diagnostic criteria and diligent observation of patients.

PMID- 12003415
TI  - Treatment of gallstones by extracorporeal shock wave lithotripsy.

PMID- 12003416
TI  - Endoluminal delivery of radiofrequency energy to the gastroesophageal junction in
      uncomplicated GERD: efficacy and potential mechanism of action.
AB  - OBJECTIVES: The endoluminal delivery of radiofrequency energy to the
      gastroesophageal junction has been shown to decrease symptoms of gastroesophageal
      reflux disease in a multicenter study. In this single-center trial, we sought to
      further examine its efficacy and physiological effects in patients with
      uncomplicated gastroesophageal reflux disease. METHODS: Patients with chronic
      heartburn requiring maintenance antisecretory therapy but without a hiatal hernia
      >2 cm, severe esophagitis, or complications of gastroesophageal reflux disease
      were prospectively studied. Radiofrequency energy was delivered to the
      gastroesophageal junction using a transorally delivered, flexible bougie-tipped
      catheter and a thermocouple-controlled generator, under sedation and analgesia.
      The primary outcome measure was effect on reflux symptoms, assessed at baseline
      and at 1, 3, and 6 months, after treatment. Other outcome measures included
      effects on antireflux medication use, quality of life, overall patient
      satisfaction, esophageal motility, esophageal acid exposure, esophageal wall
      thickness, appearance of the cardioesophageal flap valve, and vagal efferent
      function. RESULTS: A total of 18 patients underwent successful outpatient
      treatment without a serious adverse event. A significant improvement in symptom
      scores (Gastroesophageal Reflux Disease [GERD] Activity Index: 112.5 [range 76.2
      140.6] vs 81.0 (74.2-97.6); p < 0.0001) and antacid use (17/wk [range 0-81] vs 0
      (0-10); p < 0.0001) was noted at 6-month follow-up. No adverse effect on
      abdominal vagal function was identified and no significant change in any
      esophageal motility parameter was seen; however, a trend was noted toward a
      reduction in the number of transient lower esophageal sphincter relaxations
      induced by gastric air distension (3.5/h vs 1.0/h, p = 0.13). No detrimental
      effects on peristalsis or swallow-induced lower esophageal sphincter relaxation
      pressure were seen. Nonsignificant trends (p = 0.06) were noted regarding a
      decrease in the Hill score and an increase in esophageal wall thickness after
      treatment. Finally, although a decrease in all pH parameters in both the upper
      and lower esophagus was seen, none reached statistical significance. CONCLUSIONS:
      Radiofrequency energy delivery to the region of the gastroesophageal junction
      provides effective symptom relief over the short term in patients with
      uncomplicated gastroesophageal reflux disease. It may achieve its therapeutic
      effect by reducing the frequency of transient lower esophageal sphincter
      relaxations triggered by gastric distension.

PMID- 12003417
TI  - Role of GERD in chronic resistant sinusitis: a prospective, open label, pilot
      trial.
AB  - OBJECTIVE: The objective of this study was to determine whether aggressive
      medical therapy of gastroesophageal reflux disease (GERD) could improve both
      subjective and objective features of chronic resistant sinusitis (CRS). METHODS:
      Consecutive patients with CRS underwent assessment of GERD and sinus symptoms,
      esophageal motility testing, dual-channel esophageal pH testing, and laryngoscopy
      and nasal endoscopy at baseline. The results were compared to those of a group of
      GERD patients without sinus problems. The CRS patients alone then received
      omeprazole 20 mg b.i.d. for 3 months with symptom follow-up at monthly intervals.
      Laryngoscopy and nasal endoscopy were repeated at 3 months. RESULTS: Eleven
      patients with CRS and 19 GERD patients participated. Eight CRS patients
      experienced heartburn at least once weekly. Esophageal manometry and pH test
      results were similar between the two groups. Nine CRS patients had an abnormal pH
      test. All 11 CRS patients completed the 3-month course of omeprazole. Individual
      sinus symptoms (nasal congestion, nasal drainage, sinus pressure, facial
      headache, malaise) and global satisfaction were modestly improved in 25-89% and
      91%, respectively, at 12 wk. Resolution of symptoms occurred infrequently. We
      identified no baseline variable that could predict symptom improvement. Although
      laryngoscopy and nasal endoscopy were abnormal in most CRS patients at baseline
      and improved in some after treatment, these changes did not parallel symptom
      improvement. CONCLUSION: In this small, prospective, open label study, we
      demonstrated a high prevalence of GERD in patients with CRS, many of whom
      experienced modest sinus symptom improvement after using omeprazole b.i.d. for 3
      months. These findings warrant further randomized, controlled study in a larger
      patient population.

PMID- 12003418
TI  - Relationship between rate of change in acid exposure along the esophagus and
      length of Barrett's epithelium.
AB  - OBJECTIVE: Gastroesophageal reflux disease (GERD) plays a major role in the
      development of Barrett's esophagus. Recently, we demonstrated that duration of
      esophageal acid exposure in the distal esophagus correlates with the length of
      Barrett's mucosa. The aim of this study was to determine whether there is a
      relationship between the rate of the change in acid exposure along the esophagus
      and the length of Barrett's esophagus. METHODS: A total of 17 patients (16 men
      and one woman; mean age 66 +/- 15 yr, range 41-83 yr) with varying lengths of
      biopsy-proven Barrett's esophagus were recruited prospectively into the study.
      Ambulatory 24-h esophageal pH monitoring was performed using a commercially
      available pH probe with four sensors located 5 cm apart. For each patient, a
      least squares regression line of the fraction of the study that the pH was <4
      against the height of the sensor above the lower esophageal sphincter was fit.
      The slope of the regression line was used to represent the rate of change in acid
      exposure. Linear regression analysis was conducted to analyze the relationship
      between the rate of change in acid exposure and the length of Barrett's mucosa.
      RESULTS: The mean Barrett's length was 5 +/- 3 cm (range 1-11 cm). Linear
      regression demonstrated a statistically significant relationship between the rate
      of change in acid exposure and the length of Barrett's esophagus for the 24-h
      duration of the study, as well as for the fraction of the study that patients
      were in the upright position (p = 0.0096 and 0.0076, respectively). For the
      supine position, the relationship did not reach statistical significance (p =
      0.095). CONCLUSIONS: We demonstrated a significant relationship between the rate
      of change in acid exposure and the length of Barrett's mucosa. Thus, as the rate
      at which recorded acid exposure values increases from the proximal to distal
      esophagus, the length of Barrett's esophagus significantly increases (for percent
      total time and upright position).

PMID- 12003419
TI  - Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or
      salvage therapy for Helicobacter pylori infection.
AB  - OBJECTIVE: Helicobacter pylori (H. pylori) eradication rates in northern Sardinia
      using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two
      antibiotics) are typically <60%, primarily because of antibiotic resistance. The
      aim of this study was to test b.i.d. quadruple therapy as primary and as salvage
      therapy in this population. METHODS: This was a prospective, single center study
      of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of
      omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth
      subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14
      days. H. pylori status was evaluated by 13C-urea breath test and histology before
      and 4-6 wk after therapy. Eradication was defined as no positive test. RESULTS:
      We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including
      15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior
      therapy: twice in 21 cases, three times in 12, and four or more times in nine.
      The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90-98%) overall,
      and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or
      smoking status. Moderate or severe side effects were experienced by only 5% of
      patients. CONCLUSIONS: Bismuth subcitrate-based b.i.d. quadruple therapy was an
      excellent primary and salvage therapy and should be considered as first line
      therapy.

PMID- 12003420
TI  - Relation of Helicobacter pylori infection to plasma vitamin B12, folic acid, and
      homocysteine levels in patients who underwent diagnostic coronary arteriography.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that chronic atrophic
      gastritis induced by Helicobacter pylori (H. pylori) causes malabsorption of
      vitamin B12 and folate in food, leading ultimately to an increase in circulating
      homocysteine levels. METHODS: We performed endoscopy with stomach biopsy and
      measured fasting plasma homocysteine, vitamin B12, and folate levels in 93
      patients who underwent diagnostic coronary arteriography. The patients were
      divided into two groups according to the presence (n = 57) or absence (n = 36) of
      H. pylori infection. Positive H. pylori infection was defined as positive H.
      pylori histology of biopsy specimens from the stomach. The extent of atrophic
      gastritis was endoscopically graded from 0 to 6. RESULTS: There were no
      differences in age, sex, or traditional coronary risk factors between the two
      groups. Atrophy scores of the stomach were greater in patients with H. pylori
      infection than in patients without (3.9 +/- 1.4 vs 2.2 +/- 1.8, p < 0.0001).
      Patients with H. pylori infection had lower levels of vitamin B12 (630 +/- 222 vs
      747 +/- 259 pg/ml, p = 0.02) and folate (6.2 +/- 2.1 vs 7.4 +/- 2.8, p = 0.046),
      as well as higher levels of homocysteine (11 +/- 4.9 vs 8.3 +/- 2.1 nmol/ml, p =
      0.01), than did patients without H. pylori infection. Plasma homocysteine levels
      correlated inversely with plasma vitamin B12 and folate levels and positively
      with atrophic scores. CONCLUSIONS: This study suggests that H. pylori-induced
      chronic atrophic gastritis decreases plasma vitamin B12 and folic acid levels,
      thereby increasing homocysteine levels. However, this effect does not seem to be
      strong.

PMID- 12003421
TI  - Duodenal erosions, a common and distinctive feature of portal hypertensive
      duodenopathy.
AB  - OBJECTIVE: The aim of the present study was to assess the presence of duodenal
      erosion and its clinical characteristics on endoscopy in patients with portal
      hypertension who had undergone endoscopic injection sclerotherapy and/or
      endoscopic variceal ligation for esophagogastric varices. METHODS: The subjects
      were 440 patients with portal hypertension, 450 with chronic hepatitis as a
      related control group, and 450 who underwent upper endoscopic examination as part
      of their routine physical examination as the controls. The underlying hepatic
      disease, hepatic function, and endoscopic findings of duodenal erosion among the
      patients with portal hypertension were studied. RESULTS: Duodenal erosion was
      found in 68 patients with portal hypertension (68 of 440, 15.5%), four patients
      with chronic hepatitis (four of 450, 0.9%), and two controls (two of 450, 0.4%).
      The incidence of duodenal erosion among the patients with portal hypertension was
      significantly higher than that in the other two groups (p < 0.01, p < 0.01,
      respectively). The lesions commonly observed in duodenitis are speckle erosions
      mainly located in the duodenal bulb. However, the most frequently seen form of
      duodenal erosion among the patients with portal hypertension extended from the
      superior portion to the descending portion, and tended to show a circular
      alignment along the Kerckring's folds. The patients with portal hypertension with
      reduced hepatic reserve capacity had more severe duodenal erosion. Endoscopic
      ultrasonography revealed thickening of the duodenal wall and proliferation of
      vascular structures within and around the wall. The histological findings of the
      duodenal erosion included edema and vascular dilation in the mucosal and
      submucosal layers. CONCLUSIONS: The location of duodenal erosion in patients with
      portal hypertension differs from that in patients with ordinary duodenitis.
      Duodenal erosion in patients with portal hypertension is considered to be one of
      the lesions of portal hypertensive duodenopathy.

PMID- 12003422
TI  - Cost-effectiveness of endoscopic ultrasonography in the evaluation of proximal
      rectal cancer.
AB  - OBJECTIVE: Clinical trials demonstrate the superiority of preoperative over
      postoperative radiotherapy (XRT) in diminishing rates of local recurrence of
      transmurally infiltrating (T3/4) rectal tumors. The dosage and cost of
      preoperative XRT are less than postoperative XRT. The economic and health impact
      of transrectal endoscopic ultrasound (EUS) on rectal cancer management has not
      been described. The aim of this study was to apply a decision analysis model to
      compare the cost-effectiveness of three staging strategies in the evaluation of
      nonmetastatic proximal rectal cancer: abdominal and pelvic CT versus abdominal CT
      plus EUS versus abdominal CT plus pelvic magnetic resonance imaging. METHODS: A
      decision model was designed using DATA Version 3.5 (TreeAge Software,
      Williamstown, MA), taking as entry criteria nonmetastatic proximal rectal cancer
      as determined by abdominal CT. In each arm, detection of transmural invasion
      prompted preoperative XRT. Baseline probabilities were varied through plausible
      ranges using sensitivity analysis. Cost inputs were based on Medicare
      professional plus facility fees. Endpoints were cost of treatment per patient and
      tumor recurrence-free rates. Cost-effectiveness (cost per prevention of local
      recurrence) and incremental cost-effectiveness ratios were calculated. RESULTS:
      For proximal rectal tumors, evaluation with abdominal CT plus EUS is the most
      cost-effective approach ($24,468/yr) compared with abdominal CT plus pelvic
      magnetic resonance imaging ($24,870) and CT alone ($26,076). Both the magnetic
      resonance imaging- and CT-only approaches were dominated (i.e., more costly and
      less effective). CONCLUSIONS: Abdominal CT plus EUS is the most cost-effective
      staging strategy for nonmetastatic proximal rectal cancer. Staging strategies
      incorporating EUS improve treatment allocation by achieving more accurate T
      staging, thereby optimizing the benefit of preoperative XRT to more advanced
      tumors.

PMID- 12003423
TI  - Acute pancreatitis in Soweto, South Africa: relationship between trypsinogen
      load, trypsinogen activation, and fibrinolysis.
AB  - OBJECTIVE: It is not known why acute pancreatitis in Soweto, South Africa,
      pursues an aggressive course. We sought clues from circulating trypsinogen load
      at admission as marker of initial acinar injury, trypsinogen activation using the
      carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the
      coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress
      markers, and antioxidant status. This article reports on the first four aspects.
      METHODS: The study involved 24 consecutive patients with a first attack. All of
      them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for
      anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was
      tested for anionic and cationic trypsinogen, alpha1 proteinase inhibitor and
      alpha2 macroglobulin. Plasma from a subset was assayed for soluble fibrin, cross
      linked fibrin degradation products (surrogates for thrombin and plasmin activity,
      respectively), and tissue-type plasminogen activator and inhibitor. RESULTS:
      Soweto controls had higher serum anionic trypsinogen (p = 0.004) and plasminogen
      activator:inhibitor ratio (p = 0.047) than U.K. controls. The outcome of acute
      pancreatitis was mild in 17 but severe in seven with three deaths, two on day 2.
      In mild pancreatitis, intense plasmin activity (p < 0.001) accompanied the surge
      in trypsinogen, especially anionic (p < 0.001), but without increased thrombin
      activity and in five patients without trypsinogen activation. In severe
      pancreatitis, further significant increments in plasmin activity and trypsinogens
      were accompanied by increased thrombin activity (p = 0.013) and trypsinogen
      activation (p = 0.046). There was no correlation between surrogates of plasmin
      and thrombin activity, or between either and the carboxypeptidase B activation
      peptide, which showed a curvilinear relationship to total serum trypsinogen.
      CONCLUSIONS: The aggressive nature of alcoholic acute pancreatitis in Soweto
      seems to reflect early profound fibrinolysis, which precedes coagulation and is
      initially independent of trypsin. Subclinical acinar-cell injury and a
      profibrinolytic diathesis in outwardly healthy Sowetans may predispose to this
      problem.

PMID- 12003424
TI  - Phantom study to determine radiation exposure to medical personnel involved in
      ERCP fluoroscopy and its reduction through equipment and behavior modifications.
AB  - OBJECTIVE: The aim of this work is to evaluate the potential radiation exposure
      to medical personnel by comparing results from phantom studies of two different
      fluoroscopic units used for ERCP, and to determine which equipment or behavior
      modification can reduce radiation exposure. METHODS: Radiation exposures using an
      opaque tissue equivalent chest phantom with an abdominal insert were performed on
      a stationary dedicated fluoroscopy unit and a mobile C-arm unit, comparing
      varying equipment manipulations. Scatter radiation was recorded at 1) the
      patients' head, 2) where the endoscopist stands, and 3) where the equipment
      personnel stands. RESULTS: Radiation exposures were significantly higher for the
      mobile C-arm unit, revealing a 4160-times greater dosage increase for head and
      neck and a 8660-times increase for body than the fixed unit. Tower position and
      vertically stationed lead shields facilitated exposure reduction by means of
      equipment manipulation. The positioning of the endoscopist away from the right
      corner of the units also decreased exposure. CONCLUSIONS: Dedicated stationary
      fluoroscopy units provide significantly less radiation exposure. Equipment and
      behavior modification including tower positioning down and vertical shielding are
      essential for reduction in radiation exposure to medical personnel.

PMID- 12003425
TI  - Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a
      cost-effectiveness analysis.
AB  - OBJECTIVES: Obstructive jaundice frequently complicates pancreatic carcinoma and
      is associated with complications such as malabsorption, coagulopathy, progressive
      hepatocellular dysfunction, and cholangitis in addition to disabling pruritus,
      which greatly interferes with terminal patients' quality of life. Endoscopic
      placement of biliary stents decreases the risk of these complications and is
      considered the procedure of choice for palliation for patients with unresectable
      tumors. We used decision analysis with Markov modeling to compare the cost
      effectivenesses of plastic stents and metal stents in patients with unresectable
      pancreatic carcinoma. METHODS: A model of the natural history of unresectable
      pancreatic carcinoma was constructed using probabilities derived from the
      literature. Cost estimates were obtained from Medicare reimbursement rates and
      supplemented by the literature. Two strategies were evaluated: 1) initial
      endoscopic plastic stent placement and 2) initial endoscopic metal stent
      placement. We compared total costs and performed cost-effectiveness analysis in
      these strategies. The outcome measures were quality-adjusted life months.
      Sensitivity analyses were performed on selected variables. RESULTS: Our baseline
      analysis showed that initial plastic stent placement was associated with a total
      cost of $13,879/patient and 1.799 quality-adjusted life months. Initial placement
      of a metal stent cost $13,466/patient and conferred 1.832 quality-adjusted life
      months. Among the variables examined, expected patient survival was demonstrated
      by sensitivity analyses to have the most influence on the results of the model.
      CONCLUSION: Initial endoscopic placement of a metal stent is a cost-saving
      strategy compared to initial plastic stent placement, particularly in patients
      expected to survive longer than 6 months.

PMID- 12003426
TI  - Factors influencing the prevalence of gallstones in liver disease: the beneficial
      and harmful influences of alcohol.
AB  - OBJECTIVE: The Patient Treatment File of the Department of Veterans Affairs
      comprises the computerized records of all inpatients treated in all Veterans
      Affairs hospitals distributed throughout the United States. This database was
      used to study the association between liver disease and clinically manifest
      cholelithiasis. METHODS: The computerized medical records of 38,459 patients with
      various forms of liver disease and 69,336 controls without the diagnosis were
      extracted from the annual files between 1990 and 1993. In a multiple logistic
      regression analysis, the occurrence of cholelithiasis served as the outcome
      variable, whereas different forms of liver disease and demographic
      characteristics, such as age, gender, and ethnicity, served as predictor
      variables. RESULTS: Among the control population, cholelithiasis was reported in
      5.2% (3,571 of 69,336) of subjects. Cholelithiasis occurred in 7.5% (2,898 of
      38,459) of patients with all liver disease, 9.5% (1,642 of 17,287) of patients
      with alcoholic liver cirrhosis, 13.7% (981 of 7,149) of patients with
      nonalcoholic liver cirrhosis, and 9.1% (66 of 728) of patients with alcoholic
      fatty liver (chi2 = 1059, df = 4, p < 0.001). In the logistic regression, the
      odds ratios (ORs) for cholelithiasis associated with various forms of liver
      disease were: in all liver diseases combined (OR = 1.31, 95% CI = 1.25-1.38), in
      alcoholic liver cirrhosis (OR = 1.62, 95% CI = 1.54-1.72), in nonalcoholic liver
      cirrhosis (OR = 2.07, 95% CI = 1.94-2.21), and in alcoholic fatty liver (OR =
      1.40, 95% CI = 1.11-1.75). Other risk factors for cholelithiasis besides liver
      disease were: female gender (OR = 1.43, 95% CI = 1.25-1.63), older age (OR = 1.28
      per age decade, 95% CI = 1.26-1.30), Native American (OR = 1.38, 95% CI = 1.12
      1.72) or Hispanic ethnicity (OR = 1.25, 95% CI = 1.15-1.35), and presence of
      diabetes mellitus (OR = 1.43, 95% CI = 1.35-1.52). A history of alcoholism
      exerted a protective influence (OR = 0.92, 95% CI = 0.87-0.97). CONCLUSION:
      Gallstone disease occurs frequently in hospitalized patients with chronic liver
      disease or liver cirrhosis and contributes to the burden of the disease.

PMID- 12003427
TI  - Bone mineral density in Crohn's disease: a longitudinal study of budesonide,
      prednisone, and nonsteroid therapy.
AB  - OBJECTIVE: Corticosteroids may contribute to the bone loss associated with
      Crohn's disease (CD). We investigated the effect on bone mineral density (BMD) of
      treatment with budesonide, a steroid with low systemic activity, and compared the
      outcome with prednisone and nonsteroid therapy in patients with CD. METHODS:
      Prospective annual BMDs of the lumbar spine (LS) and femoral neck (FN) were
      measured for 2 yr in 138 patients with quiescent CD treated with mean daily doses
      of 8.5 mg of budesonide (n = 48), 10.5 mg of prednisone (n = 45), or nonsteroid
      drugs (n = 45). RESULTS: Between baseline and 1 yr, the mean LS BMD decreased
      2.36% in the budesonide group (p < 0.001), 0.61% in the prednisone group (ns),
      and 0.09% in the nonsteroid group (ns). The difference between budesonide and
      nonsteroid groups was significant (p = 0.003). In the 2nd yr, LS BMD did not
      change in the three groups. After 2 yr, FN BMD decreased 2.94% in the budesonide
      group (p < 0.01), 0.36% in the prednisone group (ns), and 1.05% in the nonsteroid
      group (ns); the differences among groups were not significant. The proportion of
      patients with bone loss of >2% per annum at the LS and FN was higher in the
      budesonide group than in the nonsteroid group (p < 0.001) and prednisone group (p
      < 0.05). CONCLUSIONS: Patients with CD receiving maintenance treatment for 2 yr
      with prednisone show little change in BMD, whereas treatment with budesonide may
      be associated with LS and FN bone loss. Budesonide does not confer an advantage
      over low-dose prednisone for the preservation of BMD.

PMID- 12003428
TI  - Immunomodulatory therapy for pediatric inflammatory bowel disease: changing
      patterns of use, 1990-2000.
AB  - OBJECTIVE: To identify changes over the past decade in physicians' attitudes
      regarding the use of immunomodulatory agents for the treatment of children with
      inflammatory bowel disease (IBD), we surveyed the membership of the North
      American Society for Pediatric Gastroenterology and Nutrition and compared the
      responses to those from an identical survey performed in 1990. METHODS: Surveys
      were mailed to 718 physicians in January, 2000. All surveys returned by mid
      February were analyzed, and results compared to those obtained in the 1990
      survey. RESULTS: Thirty-nine percent (278/718) of surveys were returned, compared
      to 27% (105/385) in 1990. Overall, 93% of the current survey's respondents agreed
      with the statement "immunomodulatory agents are effective in the treatment of
      children and adolescents with IBD." Compared to 1990, significant increases (p <
      0.0001) were noted in the percentage of respondents who prescribe
      immunomodulatory agents to children with all forms of IBD. Indications for
      immunomodulation that showed significant increases (p < 0.001) since 1990
      included treatment of perianal and non-perianal fistulae; growth failure; use as
      initial, primary therapy; and use as prophylaxis against postoperative
      recurrence. 6-Mercaptopurine and azathioprine continue to be the agents
      prescribed by the greatest percentage of respondents. More physicians are willing
      to use immunomodulatory agents in children younger than 5 yr, and duration of use
      is longer than in 1990. Currently, physicians seem to favor the use of
      immunomodulatory agents over colectomy for children with either intractable
      ulcerative or Crohn's colitis. Most respondents remain concerned about potential
      bone marrow and immune suppression, but concerns regarding malignancy,
      teratogenicity, and infertility have lessened. CONCLUSION: These survey findings
      document that pediatric gastroenterologists have widely accepted the use of
      immunomodulators in the treatment of children and adolescents with IBD.

PMID- 12003429
TI  - The insensitivity of endoscopic markers in celiac disease.
AB  - OBJECTIVES: Celiac disease (CD) is characterized by small intestinal inflammation
      and mucosal atrophy. Endoscopic markers of villous atrophy are reported to be
      present in 88-100% of untreated celiac patients. In patients being evaluated for
      iron deficiency anemia (IDA), we examined whether endoscopic markers could
      predict histological results consistent with CD. METHODS: One hundred thirteen
      patients without histories of CD had small bowel biopsies to evaluate IDA using
      videoendoscopy. Markers suggesting villous atrophy were noted at endoscopy.
      Biopsy specimens were reviewed for consistency with CD. Endoscopic and
      histological findings were compared. RESULTS: Seventeen patients were diagnosed
      with CD, both clinically and histologically. Loss of folds was the most sensitive
      marker of villous atrophy, present in 47% with CD, with 97% specificity. The
      mosaic pattern was much less sensitive (12%), with 100% specificity. Nodularity
      and scalloping had low sensitivities (6%), but specificities of 95% and 100%,
      respectively. A finding of any endoscopic marker yielded a sensitivity of 59% and
      specificity of 92% for CD. CONCLUSIONS: Although endoscopic markers have been
      guides for directing small bowel biopsies in patients suspected of having CD, we
      found sensitivities of these markers to be low and conclude that they should not
      be relied upon for detecting CD in patients presenting with IDA.

PMID- 12003430
TI  - Changes in the bacterial flora of the neoterminal ileum after ileocolonic
      resection for Crohn's disease.
AB  - OBJECTIVE: Bacterial agents have been implicated in the early recurrence of
      Crohn's disease after ileocolectomy. The aim of our study was to identify and
      quantify bacteria associated with the ileal mucosa in patients and controls and
      to correlate specific bacteria with recurrence. METHODS: The predominant
      bacterial microflora of the ileum were enumerated and identified, aerobically and
      anaerobically, in biopsies obtained at the time of surgery or by endoscopy from
      61 patients with Crohn's disease and 10 ileocolectomy controls. The 61 specimens
      were comprised of 13 ileal biopsies taken from resection specimens, seven taken
      after ileostomy, and 41 taken after ileocolectomy. RESULTS: Ileocolectomy induced
      a significant increase in bacterial counts and variety in the neoterminal ileum
      in both patients and controls that was not observed in ileostomy biopsies.
      Comparison between patients and controls revealed greater numbers of Escherichia
      coli and enterococci in Crohn's disease and of bifidobacteria and ruminococci in
      controls. Early recurrence was associated with high counts of E. coli and
      bacteroides and the frequent isolation of fusobacteria. CONCLUSION: After
      ileocolectomy, colonization of the neoterminal ileum is increased. Our data
      suggest that increases in the populations of specific bacteria such as E. coli,
      enterococci, bacteroides, and fusobacteria may be important in postoperative
      recurrence of Crohn's disease.

PMID- 12003431
TI  - Long term outcome of patients with active Crohn's disease exhibiting extensive
      and deep ulcerations at colonoscopy.
AB  - OBJECTIVE: Prediction of the clinical course of Crohn's disease (CD) is difficult
      in the long term. Our aim was to determine whether the presence of severe
      endoscopic lesions (SELs) may predict a higher risk of colectomy and penetrating
      complications. METHODS: All patients at our institution with active ileocoIonic
      CD who had colonoscopies between 1990 and 1996 were included in the study. SELs
      were defined as extensive and deep ulcerations covering more than 10% of the
      mucosal area of at least one segment of the colon. RESULTS: Among the 102
      patients included, 53 had SELs at index colonoscopy. During the follow-up (median
      = 52 months), 37 patients underwent colonic resection. Probabilities of colectomy
      at 1, 3, and 8 yr were 20%, 26%, and 42%. Risk of colectomy was independently
      affected by the presence of SELs at index colonoscopy (relative risk [RR] = 5.43,
      95% CI = 2.64-11.18), a Crohn's Disease Activity Index level greater than 288 (RR
      = 2.21, 95% CI = 1.09-4.47), and the absence of immunosuppressive therapy during
      the follow-up (RR = 2.44, 95% CI = 1.20-5.00). Probabilities of colectomy were,
      respectively, 31% and 6% at 1 yr, 42% and 8% at 3 yr, and 62% and 18% at 8 yr in
      patients with and without SELs. We performed a second analysis excluding the 14
      patients operated on within the 3 months after the index colonoscopy: presence of
      SELs remained the only significant factor predictive of colectomy (RR = 6.72, 95%
      CI = 2.26-20.03). All six patients with penetrating complications during the
      follow-up had SELs at index colonoscopy. CONCLUSIONS: Patients with CD exhibiting
      deep and extensive ulcerations at colonoscopy have a more aggressive clinical
      course with an increased rate of penetrating complications and surgery.

PMID- 12003432
TI  - Hypnotherapy in irritable bowel syndrome: a large-scale audit of a clinical
      service with examination of factors influencing responsiveness.
AB  - OBJECTIVES: Hypnotherapy has been shown to be effective in the treatment of
      irritable bowel syndrome in a number of previous research studies. This has led
      to the establishment of the first unit in the United Kingdom staffed by six
      therapists that provides this treatment as a clinical service. This study
      presents an audit on the first 250 unselected patients treated, and these large
      numbers have also allowed analysis of data in terms of a variety of other
      factors, such as gender and bowel habit type, that might affect outcome. METHODS:
      Patients underwent 12 sessions of hypnotherapy over a 3-month period and were
      required to practice techniques in between sessions. At the beginning and end of
      the course of treatment, patients completed questionnaires to score bowel and
      extracolonic symptoms, quality of life, and anxiety and depression, allowing
      comparisons to be made. RESULTS: Marked improvement was seen in all symptom
      measures, quality of life, and anxiety and depression (all ps < 0.001), in
      keeping with previous studies. All subgroups of patients appeared to do equally
      well, with the notable exception of males with diarrhea, who improved far less
      than other patients (p < 0.001). No factors, such as anxiety and depression or
      other prehypnotherapy variables, could explain this lack of improvement.
      CONCLUSIONS: This study clearly demonstrates that hypnotherapy remains an
      extremely effective treatment for irritable bowel syndrome and should prove more
      cost-effective as new, more expensive drugs come on to the market. It may be less
      useful in males with diarrhea-predominant bowel habit, a finding that may have
      pathophysiological implications.

PMID- 12003433
TI  - The IBS-36: a new quality of life measure for irritable bowel syndrome.
AB  - OBJECTIVE: We aimed to develop and validate a quality of life instrument for
      patients with irritable bowel syndrome (IBS). METHODS: Using focus groups,
      existing questionnaires, and literature reviews, five IBS patients and nine
      gastroenterologists compiled and pilot tested for content validity a 70-item
      questionnaire. The questionnaire was then administered to 107 IBS patients, and
      using these data, the 70-item questionnaire was reduced to 36 questions through
      statistical and consensus methodology. The IBS-36 questionnaire was tested for
      construct validity, reliability, reproducibility, and responsiveness using a gold
      standard of structured interviews by three gastroenterologists, the Medical
      Outcomes Study Short Form Quality of Life Questionnaire, and the Coping Resource
      Inventory. RESULTS: The IBS-36 consists of 36 questions scored on a 7-point
      Likert scale. It has a very high internal consistency (Cronbach's alpha = 0.95)
      and a high test-retest reliability (Spearman's r = 0.92) and correlates as
      hypothesized with the Medical Outcomes Study Short Form Quality of Life
      Questionnaire (p < 0.001), McGill pain scores (p < 0.001), and IBS patient
      reported sleep, symptom, and pain scores (ps = 0.030, <0.001, and <0.001,
      respectively). CONCLUSIONS: The IBS-36 addresses all areas of quality of life
      affected by IBS and is easy to administer and score. The IBS-36 is a well
      validated, condition-specific quality of life measure for IBS patients that is
      sensitive to clinical intervention and highly correlated with established quality
      of life measures and patient-reported symptom scores.

PMID- 12003434
TI  - Irritable pouch syndrome: a new category of diagnosis for symptomatic patients
      with ileal pouch-anal anastomosis.
AB  - OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone. However,
      increased stool frequency, urgency, and abdominal pain could be due to a
      condition resembling irritable bowel syndrome. This study was designed to assess
      the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI).
      METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive
      symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis.
      Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as
      endoscopic and histological inflammation of the rectal cuff and no inflammation
      of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a
      PDAI of <7 and the absence of cuffitis. RESULTS: Thirty-one patients (50.8%) had
      pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were
      similar in the three groups. Increased stool frequency, urgency, and abdominal
      cramps were the most common symptoms in the three groups. Rectal bleeding was
      seen only in cuffitis (p < 0.001). No patient in the three groups had fever.
      Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of
      ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All
      four patients with cuffitis responded to topical hydrocortisone or mesalamine
      with a reduction in the PDAI symptom component score of > or = 1. Twelve patients
      with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or
      antidepressant therapies with a reduction in the PDAI symptom component score of
      > or = 1, whereas the remaining patients had persistent symptoms despite therapy.
      CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch-anal
      anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis
      and have been classified as having IPS. There is an overlap of symptoms among
      patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can
      differentiate among these groups. Distinction between these three groups has
      therapeutic implications.

PMID- 12003435
TI  - Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver.
AB  - OBJECTIVE: Bone loss frequently appears in the natural history of liver disease.
      The effects of therapy for osteoporosis associated with cirrhosis of the liver
      are still controversial. We evaluated the effects of vitamin K2 on osteopenia in
      women with cirrhosis. METHODS: The subjects were 50 women with cirrhosis who had
      underlying hepatitis viral infections. Half of the patients were randomly
      assigned to receive vitamin K2 (menatetrenone). The bone mineral density (BMD) of
      the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at entry
      and at 1-yr intervals for 2 yr. RESULTS: The percentages of change from the
      initial BMD at 1 and 2 yr after initiation of the study were, respectively, +0.1
      +/- 2.6% and -0.5 +/- 3.5% for the vitamin K2-treated group and -2.2 +/- 2.4% and
      -4.6 +/- 3.9% for the control group. The changes in BMD at each timepoint
      differed significantly between the control and treated groups (p = 0.008 for 1 yr
      and p = 0.002 for 2 yr). In the vitamin K2-treated group, the ratio of
      osteocalcin to undercarboxylated osteocalcin in those patients with increases in
      BMD after 1 yr of treatment was significantly lower than that in patients showing
      decreases in BMD (p = 0.017). No adverse effects of vitamin K2 were noted.
      CONCLUSIONS: Vitamin K2 can prevent bone loss and may therefore be useful in the
      management of bone disease in women with cirrhosis of the liver.

PMID- 12003436
TI  - Hepatic iron overload does not prevent a sustained virological response to
      interferon-alpha therapy: a long term follow-up study in hepatitis C-infected
      patients with beta thalassemia major.
AB  - OBJECTIVES: Transfusion-acquired chronic hepatitis C infection and systemic iron
      overload are common in patients with beta thalassemia major. The magnitude of
      hepatic iron overload has been associated with a poor response to interferon
      based antiviral therapy for hepatitis C. The aim of this study was to evaluate
      the effect of hepatic iron concentration (HIC) on response to interferon
      monotherapy in patients with massive hepatic iron overload. METHODS: Twenty-eight
      patients with beta thalassemia major, transfusion-acquired iron overload, and
      chronic hepatitis C infection were prospectively treated with interferon for 6
      months. HIC was measured by atomic absorption spectroscopy before treatment.
      Serum iron, ferritin, hepatitis C virus genotype, viral load, and liver histology
      were analyzed. RESULTS: Eight patients (28%) achieved a sustained virological
      response that has been durable after a mean of 66 months of follow-up. The median
      HIC was 2583 microg/g dry weight. There was no difference in HIC between
      responders and nonresponders to therapy. Serum hepatitis C virus RNA was lower in
      responders than in nonresponders. Genotype 1 was more frequent in nonresponders,
      and non-1 genotypes were more frequent in responders, although this did not reach
      statistical significance because of patient numbers. CONCLUSIONS: A long term
      response to interferon is unrelated to HIC in this patient group, and a durable
      response can occur despite massive iron overload. HIC may be a factor in liver
      cell injury, but it does not reliably predict a response to interferon therapy.

PMID- 12003437
TI  - Amino acid substitutions in the nonstructural region 5A of hepatitis C virus
      genotypes 2a and 2b and its relation to viral load and response to interferon.
AB  - OBJECTIVES: The interferon sensitivity-determining region (ISDR) in nonstructural
      region 5A (NS5A) of hepatitis C virus genotype 1b has been reported to correlate
      with response to interferon therapy and viral load. Recently the correlation
      between NS5A and response to interferon in genotype 2a was also reported. We
      examined the region of genotypes 2a and 2b corresponding to the ISDR of genotype
      lb to elucidate its correlation with response to interferon and viral load.
      METHODS: The sequences of amino acid positions 2213-2248 in NS5A were determined
      in 39 patients with genotype 2a and 12 patients with genotype 2b. RESULTS: In the
      patients infected with genotype 2a, the number of amino acid substitutions in the
      ISDR-corresponding region compared with the consensus sequence of genotype 2a was
      significantly correlated with viral load (p = -0.541, p < 0.001) and with
      response to interferon therapy (p < 0.05); 83% of the patients with three or more
      substitutions obtained sustained responses, whereas only 44% of those with less
      than three substitutions obtained sustained responses. Multivariate analysis
      confirmed that the number of substitutions in the ISDR-corresponding region of
      genotype 2a was one of the independent predictors of response to interferon
      therapy (discriminant coefficient = 1.35, p < 0.001). CONCLUSIONS: Substitutions
      in the ISDR-corresponding region in NS5A of hepatitis C virus genotype 2a was
      confirmed to correlate to viral load and response to interferon therapy. In
      genotype 2b, further work must be considered because of the small number of
      patients studied.

PMID- 12003438
TI  - Antimitochondrial antibody profiles: are they valid prognostic indicators in
      primary biliary cirrhosis?
AB  - OBJECTIVE: Retrospective studies have reported that subtypes of antimitochondrial
      antibodies (AMAs) discriminate between a benign and a progressive course in
      patients with primary biliary cirrhosis (PBC). Four AMA profiles (A-D) were
      defined: profiles A and B associated with a benign course and C and D with a
      progressive course. We aimed to confirm whether AMA profiles predict prognosis in
      a large sample of North American patients with PBC. METHODS: Stored pretreatment
      sera from patients with PBC from two centers were tested for AMA profiles using
      standard techniques. Proportions of patients in each profile group reaching the
      endpoints of liver transplantation or death from liver disease were compared.
      Kaplan-Meier curves were constructed comparing AMA profiles. RESULTS: All 472
      patients studied had AMA positive, biopsy-confirmed PBC. Mean age at diagnosis
      was 53 yr, 90% were female, mean follow-up was 7.6 yr (range = 0.5-23), and 51%
      received ursodeoxycholic acid for >6 months. Profile A was not detected; 16.7%
      had profile B; 51.1%, profile C; and 32.2%, profile D. Duration of follow-up was
      comparable among the different profile groups. The proportions of patients
      reaching endpoints of death from liver disease or transplantation did not differ
      among the AMA profiles. No difference in the Kaplan-Meier curves between the
      different profile groups was observed (p > 0.05). CONCLUSION: AMA profiles do not
      predict prognosis in patients with PBC.

PMID- 12003439
TI  - Elk velvet antler in rheumatoid arthritis: phase II trial.
AB  - The purpose of this phase II clinical trial was to examine safety of elk velvet
      antler taken concurrently with rheumatoid arthritis medications and to determine
      efficacy by dose to enable sample size estimation and dose standardization for a
      larger study. Forty patients with stage II rheumatoid arthritis were randomly
      assigned to 1 of 4 arms of 10 patients each. One group received placebo and the
      other 3 groups received 2, 4, or 6 capsules (215 mg) of elk velvet antler with
      appropriate placebos to total 6 capsules daily. All subjects continued to take
      their arthritis medications. Outcome variables were reported adverse events and
      health status. At 1 month, there were no significant differences between groups
      in number of adverse events or health status. The greatest improvement was in the
      6 elk velvet antler group, the least was in the placebo group. Differences were
      not statistically significant. It was concluded that elk velvet antler can be
      taken safely in conjunction with a number of rheumatoid arthritis medications and
      should be studied further to assess efficacy.

PMID- 12003440
TI  - Effects of separation and separation with supplemental stroking in BALb/c infant
      mice.
AB  - The purpose of this pilot study was to investigate selected stress, immune, and
      growth consequences of maternal separation and separation with supplemental
      stroking in neonatal BALB/c infant mice and their dams. Three groups of 5 litters
      each (7 pups per litter) were studied. Control litters were undisturbed.
      Separated litters experienced 3 h of daily maternal deprivation on postnatal days
      6 to 10. Separated/stroked litters were separated also, but for 2 h, which was
      then followed by 1 h of stroking with a wet paintbrush to simulate maternal
      tactile stimulation. After the experimental period, all animals were returned to
      the nest and left undisturbed for 5 additional days. One pup from each litter was
      sacrificed on postnatal days 6, 8, 10, and 15. Spleens and thymuses were removed,
      weighed, and homogenized for cell sorting, cytokine analysis, and proliferation
      studies. Blood was drawn for corticosterone levels and hematocrit. Hematocrits
      and thymus weights were lower in separated mice, suggesting decreased growth and
      protein synthesis. Separated/stroked pups had increased splenic proliferation
      responses to conconavalin A and phytohemagglutinin at day 15. Separated dams'
      proliferative response to ConA was lower than control dams at day 15. Day 15
      decreases in thymic CD8 cells occurred in pups, with an increased thymic H:S
      ratio in separated pups. CD90 cells were higher at day 15 in separated/stroked
      pups as were CD25s at day 10 in spleen and thymus. However, gene expression of
      cytokines was not measurable in spleen and thymic cells, with the exception of
      gamma-IFN in separated/stroked animals. Pooled organ homogenates were used in
      this preliminary work, and further studies are needed to more precisely analyze
      the stress, immune, and growth effects of these interventions.

PMID- 12003441
TI  - Physiologic factors contributing to a transition in oral immunity among
      mechanically ventilated adults.
AB  - Ventilator-associated pneumonia (VAP), a specific type of nosocomial pneumonia,
      occurs in approximately 21% of patients in intensive care, and the mortality can
      be as high as 71%. VAP causes considerable mortality and morbidity, and it
      exponentially increases health care costs. The incidence of VAP is associated
      with oropharyngeal colonization of gram-negative bacteria. Within 48 h of
      hospital admission, the composition of the oropharyngeal flora of critically ill
      patients undergoes a change from the usual gram-positive streptococci and dental
      pathogens to a predominant gram-negative flora that includes more virulent
      organisms, which predispose patients to VAP. Identification and understanding of
      this oral transition from gram-positive to predominantly gram-negative flora may
      assist health care professionals in differentiating among oral immune markers
      that suggest compromised immunity. The purpose of this article is to provide a
      review of the literature that promotes an understanding of current knowledge
      about the transition of oral immunity in mechanically ventilated patients.

PMID- 12003442
TI  - Treatment and prevention of diaphragm fatigue using low-dose dopamine.
AB  - There is increasing evidence that diaphragm fatigue is a major cause of failure
      in weaning patients from mechanical ventilation. Patients in intensive care units
      are often administered dopamine to improve renal blood flow without regard to its
      effect on diaphragm blood flow. The aim of this study was to investigate if
      intravenous low-dose dopamine, equivalent to the dose used in intensive care
      units, can treat and prevent diaphragm fatigue. Diaphragm fatigue was produced in
      anesthetized rats by inspiratory resistance loading (IRL). The effect on
      diaphragm shortening, diaphragm blood flow, and aortic blood flow was determined.
      When diaphragm fatigue was attained, group I was given saline for 30 min while
      maintaining IRL. At the time of diaphragm fatigue, group II was given low-dose
      dopamine (2 microg/kg/min) for 30 min while maintaining IRL. In group III,
      dopamine administration was started before and continued throughout the period of
      IRL. Administering dopamine after the development of diaphragm fatigue (group II)
      increased diaphragm performance as measured by increased diaphragm shortening and
      was accompanied by an increased diaphragm blood flow. Administering dopamine
      prior to and throughout IRL (group III) prevented diaphragm fatigue. Low-dose
      dopamine can prevent and/or reverse diaphragm fatigue in rats without a
      significant change in aortic blood flow. This effect of dopamine may be due to
      increased oxygen delivery associated with the increased diaphragm blood flow,
      resulting in less free radical formation and thus less muscle damage.

PMID- 12003443
TI  - Preterm infant temperature circadian rhythm: possible effect of parental
      cosleeping.
AB  - The purpose of this study was to describe the circadian rhythm of abdominal skin
      temperature and explore factors related to the timing of circadian rhythm
      acrophase. Thirty-four preterm infants (gestational age 26 to 33 weeks) were
      studied in the home environment at 44 to 46 weeks postconceptional age. Insulated
      abdominal skin was monitored continuously, and parents recorded sleep/wake
      activity over a 24-h period. Circadian rhythm was analyzed using cosinor
      analysis. Using MANCOVA, the effects of cosleeping, feeding method, night
      feeding, hospital stay, time home, and illness on acrophase were determined.
      Infants demonstrated evidence of developing circadian rhythm of temperature.
      Cosleeping and length of hospital stay were significantly related to acrophase.
      The mean acrophase for cosleeping infants was 07:44 (95% confidence interval =
      05:12, 11:08), whereas that for non-cosleeping infants was 22.05 (95% confidence
      interval = 17:31, 01:42). Proximity with parents during nighttime hours may serve
      to entrain preterm infant circadian rhythm.

PMID- 12003444
TI  - Cognitive impairments associated with formal thought disorder in people with
      schizophrenia.
AB  - Formal thought disorder (FTD), or disorganized speech, is one of the central
      signs of schizophrenia. Despite extensive research, the cognitive processes
      associated with FTD are still unclear. However, the authors' review of FTD
      theories and research indicates that considerable progress has been made in
      identifying possible cognitive impairments associated with FTD. Specifically, FTD
      is strongly associated with impaired executive functioning and with impaired
      processing of semantic information. Their review indicates that previous research
      has not yet supported an association between FTD and either an increase in
      spreading activation or an impairment within the language production system.

PMID- 12003445
TI  - Anxiety-related attentional biases and their regulation by attentional control.
AB  - This study examined the role of self-reported attentional control in regulating
      attentional biases related to trait anxiety. Simple detection targets were
      preceded by cues labeling potential target locations as threatening (likely to
      result in negative feedback) or safe (likely to result in positive feedback).
      Trait anxious participants showed an early attentional bias favoring the
      threatening location 250 ms after the cue and a late bias favoring the safe
      location 500 ms after the cue. The anxiety-related threat bias was moderated by
      attentional control at the 500-ms delay: Anxious participants with poor
      attentional control still showed the threat bias, whereas those with good control
      were better able to shift from the threatening location. Thus, skilled control of
      voluntary attention may allow anxious persons to limit the impact of threatening
      information.

PMID- 12003446
TI  - The course of anhedonia during 10 years of schizophrenic illness.
AB  - Although anhedonia has been proposed to be a trait-like characteristic in
      schizophrenia patients, its persistence and stability have not been tested using
      multiple assessments over a multiyear period. Specific definitions of anhedonia
      vary across studies, and relationships between different types of anhedonia as
      well as their relationship to schizophrenic symptoms over the course of illness
      have not been addressed. The current research, using prospectively collected
      longitudinal data covering a 10-year span for 127 individuals with schizophrenic
      illness, found that (a) physical, but not depressive, anhedonia is a stable
      characteristic over a 10-year period; (b) physical anhedonia does not show strong
      and consistent relationships with psychotic, negative, or depressive symptoms;
      and (c) the relationship between some premorbid characteristics and physical
      anhedonia are significant even 10 years into the course of illness.

PMID- 12003447
TI  - A direct assessment of the role of state and trait negative emotion in aggressive
      behavior.
AB  - Affective priming of aggression was examined in groups low and high in trait
      negative emotionality (NEM) using a Buss aggression paradigm. Negative affect was
      induced by exposure to aversive air blasts during some intervals (threat) and not
      others (safe). Phasic negative affect was assessed using startle reflex
      potentiation, and tonic distress was indexed by startle sensitization.
      Participants delivered shocks faster during threat versus safe intervals,
      indicating that phasic distress primed aggression. Following initial exposure to
      air blasts, high NEM participants showed enhanced tonic distress and delivered
      persistently more intense shocks than low NEM participants. These findings
      indicate that sustained negative affect biases high stress-reactive individuals
      toward more intense acts of aggression, with phasic distress affecting the
      rapidity of aggressive response.

PMID- 12003448
TI  - Neurophysiological markers of vulnerability to schizophrenia: sensitivity and
      specificity of specific quantitative eye movement measures.
AB  - Eye-tracking deficits in schizophrenic patients and relatives have generated
      interest in using eye movements to mark schizophrenia liability. Efforts to
      develop specific quantitative measures have provided insight into the nature of
      the deficit and suggested what underlying neurophysiological mechanisms are
      involved. This study used receiver operating characteristic curve analyses to
      evaluate and compare the sensitivity, specificity, and overall accuracy of
      predicting disease liability using single and combined specific and global
      quantitative measures. Results indicate that measures of predictive pursuit and
      leading saccades significantly increased predictive accuracy compared with
      traditional global measures. Combining specific measures provided greater
      predictive accuracy compared with single measures. Implications for the use of
      specific eye movement measures to define schizophrenia-related phenotypes in
      genetic studies are discussed.

PMID- 12003449
TI  - The persistence of attention-deficit/hyperactivity disorder into young adulthood
      as a function of reporting source and definition of disorder.
AB  - This study examined the persistence of attention-deficit/hyperactivity disorder
      (ADHD) into young adulthood using hyperactive (N = 147) and community control (N
      = 71) children evaluated at ages 19-25 years. ADHD was rare in both groups (5%
      vs. 0%) based on self-report but was substantially higher using parent reports
      (46% vs. 1.4%). Using a developmentally referenced criterion (+2 SD), prevalence
      remained low for self-reports (12% vs. 10%) but rose further for parent reports
      (66% vs. 8%). Parent reports were more strongly associated with major life
      activities than were self-reports. Recollections of childhood ADHD showed
      moderate correlations with actual parent ratings collected in childd hood, which
      suggests some validity for such recollections. The authors conclude that previous
      follow-up studies that relied on self-reports might have substantially
      underestimated the persistence of ADHD into adulthood.

PMID- 12003450
TI  - The latent structure of posttraumatic stress disorder: a taxometric investigation
      of reactions to extreme stress.
AB  - Mental health professionals have debated whether posttraumatic stress disorder
      (PTSD) can be qualitatively distinguished from normal reactions to traumatic
      events. This debate has been fueled by indications that many trauma-exposed
      individuals evidence partial presentations of PTSD that are associated with
      significant impairment and help-seeking behavior. The authors examined the latent
      structure of PTSD in a large sample of male combat veterans. Three taxometric
      procedures-MAMBAC, MAXEIG, and L-Mode-were performed with 3 indicator sets drawn
      from a clinical interview and a self-report measure of PTSD. Results across
      procedures, consistency tests, and analysis of simulated comparison data all
      converged on a dimensional solution, suggesting that PTSD reflects the upper end
      of a stress-response continuum rather than a discrete clinical syndrome.

PMID- 12003451
TI  - Crying threshold and intensity in major depressive disorder.
AB  - Clinical lore suggests that depression is associated with frequent and intense
      crying. To test these postulations empirically, a standardized cry-evoking
      stimulus was presented to depressed and nondepressed participants, and their
      likelihood of crying and the magnitude of crying-related changes in their emotion
      experience, behavior, and autonomic physiology were compared. Unexpectedly,
      crying was no more likely in depressed than in nondepressed participants. Within
      the nondepressed group, participants who cried exhibited increases in the report
      and display of sadness and had greater cardiac and electrodermal activation than
      did participants who did not cry. There was less evidence of this crying-related
      emotional activation within the depressed group. The lack of emotional activation
      among clinically depressed participants who cried provides a tantalizing clue
      concerning how emotions are dysregulated in this disorder.

PMID- 12003452
TI  - Idiom processing in schizophrenia: literal implausibility saves the day for idiom
      priming.
AB  - Schizophrenia patients have difficulty processing nonliteral forms of discourse
      such as idiomatic expressions. We hypothesized that schizophrenia patients would
      show impaired idiom processing for literally plausible idioms (e.g., kick the
      bucket) but not for literally implausible idioms (e.g., be on cloud nine). Thirty
      two patients and 36 controls listened to sentences containing literally plausible
      and implausible idioms and made lexical decisions about idiom-related or literal
      related targets. Schizophrenia patients showed reduced priming for literally
      plausible idioms but intact priming for literally implausible idioms compared
      with controls. Both groups showed evidence of literal word priming. These results
      are consistent with the notion that schizophrenia patients make normal use of
      context under conditions that minimize the need for controlled processing.

PMID- 12003453
TI  - Interpretation revealed in the blink of an eye: depressive bias in the resolution
      of ambiguity.
AB  - Self-report measures of interpretation have been criticized on methodological
      grounds. An approach is introduced in this article that enables the assessment of
      interpretive bias with a greater degree of methodological rigor than previously
      has been the case. Psychophysiological researchers have established that the
      magnitude of the human blink reflex is augmented when elicited during negative
      rather than neutral imagery. The 1st experiment demonstrates that the blink
      reflex is sensitive to the emotional valence of imagery evoked by interpretations
      imposed on ambiguous stimuli. In the 2nd experiment, this measure is used to
      assess interpretations imposed on ambiguous stimuli by individuals who differ in
      depression levels. The findings are consistent with the hypothesis that
      depression is associated with a negative interpretive bias.

PMID- 12003454
TI  - Men who molest their sexually immature daughters: is a special explanation
      required?
AB  - Child molesters who target their own children have been described as low risk and
      not pedophilic. Men who had molested a daughter or stepdaughter (n = 82) were
      compared to 102 molesters whose only female victims were extrafamilial. Men who
      offended against their own daughters had less deviant sexual age preferences and
      were less likely to commit new violent and sexual offenses. However, the father
      daughter molesters exhibited an average absolute phallometric preference for
      prepubertal children and had a violent recidivism rate of 22% in a follow-up of
      less than 5 years. Actuarial risk assessment instruments (the Violence Risk
      Appraisal Guide and the Sex Offender Risk Appraisal Guide; V. L. Quinsey, G. T.
      Harris, M. E. Rice, and C. A. Cormier, 1998) worked as well for intrafamilial
      child molesters as for other sex offenders.

PMID- 12003455
TI  - Expressed emotion and attributions in the carers of patients with Alzheimer's
      disease: the effect on carer burden.
AB  - Burden of care, expressed emotion (EE), causal attributions, and salivary
      cortisol were assessed in 100 carers of patients with Alzheimer's disease. Forty
      one carers were rated high EE, which was associated with higher scores of carer
      distress and strain, and greater reports of noncognitive features in the patient,
      but not with cortisol levels. High EE carers made more attributions personal to,
      and controllable by, the patient for negative events. Critical carers made more
      attributions of the patient's behavior that was idiosyncratic. Warmth toward the
      patient was associated with the opposite of this pattern. Overinvolved carers
      made attributions of the patient's behavior to causes external to the patient and
      internal to themselves. Cortisol levels were associated with self-reports of
      strain and distress.

PMID- 12003456
TI  - Response styles among patients with minor depression and dysthymia in primary
      care.
AB  - Ruminative responses to depression have predicted duration and severity of
      depressive symptoms. The authors examined how response styles change over the
      course of treatment for depression and as a function of type of treatment. They
      also examined the ability of response styles to predict treatment outcome and
      status at follow-up. Primary care patients (n = 96) with dysthymia or minor
      depression were randomly assigned to problem-solving therapy, paroxetine, or
      placebo. Patients' depressive symptoms and rumination, but not distraction,
      decreased over time. Pretreatment rumination and distraction were associated with
      more depressive symptoms at the conclusion of treatment; the latter finding was
      not consistent with the response style theory of depression. Results are
      discussed in terms of their implications for this theory.

PMID- 12003457
TI  - Electrophysiological evidence reveals affective evaluation deficits early in
      stimulus processing in patients with panic disorder.
AB  - Cognitive and neurobiological accounts of clinical anxiety and depression were
      examined via event-related brain potentials (ERPs) recorded from patients with
      panic disorder and healthy controls as they performed an old/new recognition
      memory task with emotionally negative and neutral words. The emotive connotation
      of words systematically influenced control subjects' - but not patients' - ERP
      effects at prefrontal sites in a latency range (to approximately 300-500 ms)
      generally assumed to reflect greater contribution of automatic than controlled
      memory processes. This provides evidence for dysfunctional inhibitory modulation
      of affective information processing in panic disorder. The ERP effects after 700
      ms, however, suggest that some patients may adopt conscious strategies to
      minimize the impact of these early processing abnormalities on overt behaviors.

PMID- 12003458
TI  - Dual-task attention deficits in dysphoric mood.
AB  - The attentional functioning of nondysphoric, mildly dysphoric, and moderately to
      severely dysphoric college students was tested using the attentional blink (AB)
      paradigm. These groups performed equally well at reporting a single target
      appearing in a rapidly presented stream of stimuli. All groups showed an AB, with
      report sensitivity for a 2nd target being reduced when the 2 targets were
      presented less than 0.5 s apart. Nondysphoric and mildly dysphoric participants
      showed the same size ABs, but the ABs for moderately to severely dysphoric
      participants were larger and longer. As predicted, the results showed that
      moderately to severely dysphoric individuals have attentional impairments. These
      impairments, however, were evident only in the more demanding dual-task
      condition.

PMID- 12003459
TI  - Genetic relationships between personality and eating attitudes and behaviors.
AB  - Genetic and environmental factors underlying relationships between personality
      traits and disordered eating were examined in 256 female adolescent twin pairs
      (166 monozygotic, 90 dizygotic). Eating behaviors were assessed with the Total
      Score, Body Dissatisfaction, Weight Preoccupation, Binge Eating, and Compensatory
      Behavior subscales from the Minnesota Eating Disorders Inventory (M-EDI; K. L.
      Klump, M. McGue, & W. G. Iacono, 2000). Personality characteristics were assessed
      with the Negative Emotionality, Positive Emotionality, and Constraint scales from
      the Multidimensional Personality Questionnaire (MPQ; A. Tellegen, 1982). Model
      fitting analyses indicated that although genetic factors were more likely to
      contribute to MPQ and M-EDI phenotypic associations than environmental factors,
      shared genetic variance between the 2 phenotypes was limited. MPQ personality
      characteristics may represent only some of several genetic risk factors for
      eating pathology.

PMID- 12003460
TI  - Hypnotic susceptibility in patients with conversion disorder.
AB  - Conversion disorder has been associated with hypnotic susceptibility for over a
      century and is currently still believed to be a form of autohypnosis. There is,
      however, little empirical evidence for the relation between hypnotic
      susceptibility and conversion symptoms. The authors compared 50 patients with
      conversion disorder with 50 matched control patients with an affective disorder
      on measures of hypnotic susceptibility, cognitive dissociation, and somatoform
      dissociation. Conversion patients were significantly more responsive to hypnotic
      suggestions than control patients. In addition, conversion patients showed a
      significant correlation between hypnotic susceptibility and the number of
      conversion complaints. These results provide the first evidence of a relationship
      between hypnotic susceptibility and the presence and number of conversion
      symptoms.

PMID- 12003461
TI  - Eat, drink, and be merry, for tomorrow we diet: effects of anticipated
      deprivation on food intake in restrained and unrestrained eaters.
AB  - This study examined the effect of anticipated food deprivation on intake in
      restrained and unrestrained eaters. Participants were randomly assigned to a diet
      condition, in which they expected to diet for a week, or to a control (no-diet)
      condition. Immediately after being assigned to a condition, participants
      completed a taste-rating task in which food consumption was measured. Restrained
      eaters in the diet condition consumed significantly more food than did restrained
      eaters in the no-diet condition or unrestrained eaters in either condition.
      Unrestrained eaters consumed the same amount regardless of condition. These
      results confirm that merely planning to go on a diet can trigger overeating in
      restrained eaters, reflecting the dynamic connection between dieting and
      overeating.

PMID- 12003462
TI  - Follow-up on "Symptoms associated with anthrax exposure: suspected 'aborted'
      anthrax".

PMID- 12003463
TI  - Unity between osteopathic and allopathic medicine only answer to preserving
      osteopathic uniqueness.

PMID- 12003464
TI  - Herbal medications should undergo rigorous evaluation.

PMID- 12003465
TI  - To kill, or not to kill...

PMID- 12003466
TI  - Defining the three-column spine.

PMID- 12003467
TI  - Potential barriers to control of blood pressure.
AB  - Numerous studies, including the National Health and Nutrition Examination Survey,
      have suggested inadequate control in patients with hypertension. Few studies have
      investigated the factors that may contribute to inadequate blood pressure
      control. This study assesses adequacy of blood pressure control in patients
      treated at two osteopathic resident-training family practice centers and
      investigates potential barriers to adequate blood pressure control in this
      setting. The care of 127 hypertensive patients was studied for 9 months. The
      charts of these patients were examined for blood pressure readings, gender,
      number of missed visits, comorbid conditions, and changes in medications. The
      adequacy of blood pressure control was assessed by the standards promulgated by
      the sixth report of the Joint National Committee guidelines. Barriers to adequate
      control, including missed visits and changes in medications, were assessed. With
      the standard of control as a mean blood pressure of less than or equal to 140/80
      mm Hg, 51.2% of the sample had controlled blood pressure. Factors that were
      associated with a significant reduction in the control of blood pressure were (1)
      patients new to the practice, (2) patients who missed follow-up visits for
      treatment of hypertension, and (3) patients who were undergoing changes in their
      medication profiles. Although rates of blood pressure control in this population
      are higher than those previously reported in the general population, they
      demonstrate room for improvement. Factors that are less under the control of
      physicians may be responsible for a large percentage of patients with
      uncontrolled hypertension. An understanding of the factors associated with poor
      blood pressure control is important in developing interventions to improve
      adequacy of blood pressure control.

PMID- 12003468
TI  - Health status and satisfaction of patients receiving ambulatory care at
      osteopathic training clinics.
AB  - Little is known about the health status and level of satisfaction of patients
      receiving care at osteopathic training clinics. Previous studies report favorable
      responses to medical student participation in ambulatory clinics. The health
      status and level of satisfaction for 2700 patients attending six family medicine
      training clinics at a college of osteopathic medicine were measured from 1996
      through 1998. Clinic response rates ranged from 74% to 98%. Data from the Medical
      Outcomes Study 36-Item Short Form (SF-36) were used to compute standardized
      scores in the following eight health scales for English- and Spanish-speaking
      patients: physical functioning, role limitations because of physical problems,
      bodily pain, general health perceptions, vitality, social functioning, role
      limitations because of emotional problems, and mental health. Patients at these
      osteopathic training clinics reported poorer health than the general population
      on all eight scales (P < .001). Patients who were English speakers reported
      significantly better health than their Spanish-speaking counterparts on four of
      the eight health scales, although the Spanish-speaking patients reported greater
      vitality. There were significant differences in patient health across clinics.
      More than 92% of patients at these six osteopathic training clinics reported that
      they were satisfied or very satisfied with their healthcare. This study suggests
      that osteopathic medical students are well accepted in ambulatory clinic
      encounters and that these students may encounter differing levels of patient
      health depending on where they receive their training.

PMID- 12003469
TI  - Impact of a tornado on a community hospital.
AB  - A significant tornado passed through the Oklahoma City metropolitan area on May
      3,1999. This study was undertaken at St Michael Hospital (Oklahoma City, Okla) to
      describe the impact on a community hospital's emergency department close to the
      tornado strike zone. Cases were defined as patients receiving diagnostic
      procedures, care, and interventions at the study hospital's emergency department
      for injuries related to the tornado. Medical records were abstracted and entered
      into a custom database; descriptive analysis was done using Microsoft Excel 97. A
      total of 147 patients met the study criteria, with an admission rate of 31 (21%)
      [corrected] of 147 patients (6 [19.4%] of 31 to the operating room, 4 [12.9%] of
      31 to the intensive care unit, and 21 [67.7%] [corrected] of 31 to ward beds). In
      addition, 4 (2.7%) of the 147 patients were transferred to tertiary-care
      facilities (3 pediatric patients with head injuries and 1 adult patient with
      spinal cord injury). Complex soft tissue wounds, head injuries, and fractures
      were the most common diagnoses. The number of head-injured patients arriving
      alive to the emergency department was higher than expected. Most soft tissue
      wounds were closed primarily in the emergency department. The authors recommend
      that preexisting referral patterns for trauma and specialty care should be a part
      of the overall disaster plans for community hospitals.

PMID- 12003470
TI  - Adnexal torsion presenting as an acute abdomen in a patient with bilateral cystic
      teratoma of the ovary.
AB  - Benign cystic teratomas are the most common ovarian neoplasms in women. Teratomas
      are usually benign, unilateral, and most often found in young and premenopausal
      women. Most are 5 cm to 10 cm in diameter when diagnosed, and on sectioning, they
      usually contain thick sebaceous material, tangled hair, and various dermal
      structures. One of the major complications seen in cystic teratoma is torsion, a
      partial or complete twisting of the ovarian suspensary pedicle causing severe
      pain, nausea, and tissue necrosis. The patient described had bilateral cystic
      teratomas, one uncommonly large and torsed, causing an acute abdomen. Discussion
      includes the diagnosis, operative management, and postoperative findings.

PMID- 12003471
TI  - Attributional biases about the origins of attitudes: externality, emotionality,
      and rationality.
AB  - Pilot work and 3 studies investigated the ways people explain the origins of
      attitudes. Study I examined the use of 3 dimensions (externality, rationality,
      emotionality) to explain the origin of people's own, in-group, and out-group
      attitudes. Attributions for own attitudes were the least externally and
      emotionally based and the most rationally based. By comparison with the out
      group, less externality, less emotionality, and more rationality also were
      attributed to in-group attitudes. Studies 2 and 3 examined the effects of
      intergroup threat on attributions for in- and out-group attitude positions. Under
      high threat, more externality and emotionality but less rationality were
      attributed to out-group attitudes than under low threat. Intergroup
      differentiation mediated the difference between out-group attributions under high
      and low threat.

PMID- 12003472
TI  - Effects of power on perceived and objective group variability: evidence that more
      powerful groups are more variable.
AB  - The perception of group variability is affected by social power and status. Three
      different mechanisms may be responsible for these effects: (a) the power of the
      perceiver affects perceived group variability; (b) the power of the perceived
      group affects its perceived variability; and (c) the power of the group affects
      its actual variability. Two studies are reported to tease apart these three
      mechanisms and provide support for the third. In the first study, high- and low
      power groups interacted and subsequently judged each other. In the second study,
      participants observed and rated the Study 1 groups, either knowing their power
      relationship or not. Results suggest that members of high-power groups manifest
      greater interpersonal variability than members of low-power groups.

PMID- 12003473
TI  - Thought confidence as a determinant of persuasion: the self-validation
      hypothesis.
AB  - Previous research in the domain of attitude change has described 2 primary
      dimensions of thinking that impact persuasion processes and outcomes: the extent
      (amount) of thinking and the direction (valence) of issue-relevant thought. The
      authors examined the possibility that another, more meta-cognitive aspect of
      thinking is also important-the degree of confidence people have in their own
      thoughts. Four studies test the notion that thought confidence affects the extent
      of persuasion. When positive thoughts dominate in response to a message,
      increasing confidence in those thoughts increases persuasion, but when negative
      thoughts dominate, increasing confidence decreases persuasion. In addition, using
      self-reported and manipulated thought confidence in separate studies, the authors
      provide evidence that the magnitude of the attitude-thought relationship depends
      on the confidence people have in their thoughts. Finally, the authors also show
      that these self-validation effects are most likely in situations that foster high
      amounts of information processing activity.

PMID- 12003474
TI  - Context and the interpretation of likelihood information: the role of intergroup
      comparisons on perceived vulnerability.
AB  - Four experiments investigated how people's perceptions about a group's (e.g.,
      women's) vulnerability to a disease are influenced by information about the
      prevalence of the disease in a comparable group (e.g., men). Participants read
      symptom and prevalence infomation about fictitious diseases before answering
      questions regarding target group vulnerability. Participants used the prevalence
      rate for a nontarget group as an immediate comparison standard for intuitively
      interpreting the degree of vulnerability of a target group, resulting in robust
      contrast effects. Experiments 3 and 4 illustrated that these contrast effects can
      cause a person's intuitive perceptions about a group's vulnerability to selected
      diseases to conflict with his or her knowledge of the prevalence rates for the
      diseases. The results support a distinction between 2 components of psychological
      uncertainty-beliefs in objective probability and more intuitive perceptions of
      certainty.

PMID- 12003475
TI  - The functional domain specificity of self-esteem and the differential prediction
      of aggression.
AB  - On the basis of an evolutionary theory of self-esteem (SE), it was hypothesized
      that the SE-aggression relationship differs across functionally distinct domains
      of SE and across contexts. In 2 experiments, participants had the opportunity to
      aggress against the evaluator of an essay they had written. In Study 1, self
      perceived superiority was positively related to aggression, whereas social
      inclusion was inversely related to aggression. In Study 2, in which the context
      was altered to simulate a mating competition, only a measure of self-perceived
      mate value emerged as a (positive) predictor of aggression. Global SE failed to
      contribute to the prediction of aggression in either experiment. Statistically
      controlling for narcissism did not eliminate either set of findings. Implications
      for the conceptualization and measurement of SE and narcissism are discussed.

PMID- 12003476
TI  - How to overcome the detrimental effects of noise in social interaction: the
      benefits of generosity.
AB  - Interpersonal misunderstanding is often rooted in noise, or discrepancies between
      intended and actual outcomes for an interaction partner due to unintended errors
      (e.g., not being able to respond to an E-mail because of a local network
      breakdown). How can one effectively cope with noise in social dilemmas,
      situations in which self-interest and collective interests are conflicting?
      Consistent with hypotheses, the present research revealed that incidents of noise
      exert a detrimental effect on level of cooperation when a partner follows strict
      reciprocity (i.e., tit for tat) but that this effect can be overcome if a partner
      behaves somewhat more cooperatively than the actor did in the previous
      interaction (i.e., tit for tat plus 1). Also, when noise was present, tit for tat
      plus 1 elicited greater levels of cooperation than did tit for tat, thereby
      underscoring the benefits of adding generosity to reciprocity in coping with
      noise in social dilemmas. The Discussion outlines implications of the present
      work for theories focusing on self-presentation and attribution, communication,
      and trust and prorelationship behavior.

PMID- 12003477
TI  - Ability evaluation by proxy: role of maximal performance and related attributes
      in social comparison.
AB  - Four experiments tested the effects of information about a proxy's related
      attributes and maximal effort in social comparisons of ability. In Study 1, a
      proxy's prior performance at maximal effort exerted systematic effects on
      participants' personal performance predictions for a novel task. When information
      about the proxy's effort was ambiguous (Study 2). information about related
      attribute similarity was used in the formulation of performance predictions. In
      Studies 3 and 4, 2-way interaction terms revealed that participants used related
      attribute information in generating performance predictions when the proxy's
      maximum effort was unknown. However, related attribute information was
      disregarded when proxy's maximum effort was unambiguous. Results were consistent
      with the proxy comparison model of ability self-evaluation (L. Wheeler, R.
      Martin, & J. Suls, 1997).

PMID- 12003478
TI  - It feels like yesterday: self-esteem, valence of personal past experiences, and
      judgments of subjective distance.
AB  - Supporting predictions from temporal self-appraisal theory, participants in 3
      studies reported feeling farther from former selves and experiences with
      unfavorable implications for their current self-view than from equally distant
      selves and experiences with flattering implications. This distancing bias
      occurred when assignment to negative and positive pasts was random, for both
      achievement and social outcomes and for single episodes as well as longer term
      experiences. Consistent with a motivational interpretation, the distancing bias
      was stronger among high than low self-esteem participants and occurred for
      personal but not for acquaintances' past events. Frequency of rehearsal and ease
      of recall of past episodes also predicted feelings of distance, but these
      variables did not account for the Self-Esteem x Valence interaction on subjective
      distancing of personal events.

PMID- 12003479
TI  - Approach-avoidance motivation in personality: approach and avoidance temperaments
      and goals.
AB  - The present research examined the role of approach and avoidance motivation in
      models of personality. Specifically, it examined the hypothesis that approach and
      avoidance temperaments represent the foundation of several basic dimensions
      espoused in the trait adjective, affective disposition, and motivational system
      approaches to personality. Factor analytic support for the hypothesis was
      obtained in Studies 1, 2, and 6; measures of extraversion, positive emotionality,
      and behavioral activation system loaded together on 1 factor (Approach
      Temperament) and measures of neuroticism, negative emotionality, and behavioral
      inhibition system loaded on another factor (Avoidance Temperament). This 2-factor
      structure was shown to be independent of response biases. In Studies 3-7,
      approach and avoidance temperaments were shown to be systematically linked to
      achievement goals (both nomothetic and idiographic). The findings are discussed
      in terms of an integrative approach to personality.

PMID- 12003480
TI  - The performance of narcissists rises and falls with perceived opportunity for
      glory.
AB  - Narcissists consider themselves to be exceptional performers, but past research
      has found no consistent relationship between narcissism and performance. The
      present research tested the hypothesis that the relationship between subclinical
      narcissism and performance is moderated by a motivational factor: perceived self
      enhancement opportunity. Four experiments were conducted, each using different
      manipulations of self-enhancement opportunity and different performance tasks. In
      each study, narcissists performed better when self-enhancement opportunity was
      high rather than low. In contrast, the performance of participants with low
      narcissism was relatively unaffected by self-enhancement opportunity. Other
      findings suggested that narcissists' self-enhancement motivation stems more from
      a desire to garner admiration than from a desire to self-evaluate. Implications
      and directions for future research are discussed.

PMID- 12003481
TI  - The regulation of explicit and implicit race bias: the role of motivations to
      respond without prejudice.
AB  - Three studies examined the moderating role of motivations to respond without
      prejudice (e.g., internal and external) in expressions of explicit and implicit
      race bias. In all studies, participants reported their explicit attitudes toward
      Blacks. Implicit measures consisted of a sequential priming task (Study 1) and
      the Implicit Association Test (Studies 2 and 3). Study 3 used a cognitive
      busyness manipulation to preclude effects of controlled processing on implicit
      responses. In each study, explicit race bias was moderated by internal motivation
      to respond without prejudice, whereas implicit race bias was moderated by the
      interaction of internal and external motivation to respond without prejudice.
      Specifically, high internal, low external participants exhibited lower levels of
      implicit race bias than did all other participants. Implications for the
      development of effective self-regulation of race bias are discussed.

PMID- 12003482
TI  - A 3-month clinical comparison of the safety and efficacy of two battery-operated
      toothbrushes: the Braun Oral-B Battery toothbrush and the Colgate Actibrush.
AB  - PURPOSE: To compare the safety and efficacy of two battery-operated, non
      rechargeable power toothbrushes, the Braun Oral-B Battery toothbrush (D4) and the
      Colgate Actibrush. MATERIALS AND METHODS: This was a randomized, single-blind,
      parallel-group study carried out over a 3-month period. A total of 114 subjects
      from a general population, who met the inclusion criteria of the study and who
      had whole mouth plaque scores of > or = 1.5 and gingivitis scores of > or = 1.2,
      participated in the study. Subjects were given either the D4 or the Colgate
      Actibrush with the manufacturers' instructions, and were asked to brush their
      teeth at home twice each day. At baseline and after 1 and 3 months, subjects were
      examined for oral hard and soft tissue health, after which they were assessed for
      gingivitis (Modified Gingival Index), bleeding (Gingival Bleeding Index), and
      plaque (Modified Quigley-Hein Plaque Index). Prior to each assessment, subjects
      refrained from all oral hygiene procedures for a period of 12-18 hours. RESULTS:
      No evidence was found of significant oral soft or hard tissue trauma, and both
      brushes were considered to be safe when used according to the manufacturers'
      instructions. In the D4 group, whole mouth, marginal and approximal plaque scores
      were significantly reduced from baseline (P < 0.05) after both 1 and 3 months by
      7-12%, whereas, in the Actibrush group, plaque scores remained relatively
      unchanged from baseline throughout the study. Furthermore, comparisons between
      the toothbrush groups showed that whole mouth, marginal and approximal plaque
      scores for the D4 were significantly lower than those for the Actibrush at both
      the 1- and 3-month assessments. Modified Gingival Index scores after 3 months
      were significantly reduced from baseline in both groups by 7-8%. Similarly,
      percentages of bleeding sites were significantly lower by 12-15%. There were no
      significant differences between the groups with respect to gingivitis scores.

PMID- 12003483
TI  - A single-use and 3-month clinical investigation of the comparative efficacy of a
      battery-operated power toothbrush and a manual toothbrush.
AB  - PURPOSE: To compare the safety and efficacy of a manual toothbrush and a battery
      operated power toothbrush in two separate studies, one utilizing a single-use
      design and the other a 3-month parallel-group design. MATERIALS AND METHODS: The
      toothbrushes compared in the two studies were the Oral-B CrossAction manual
      toothbrush and the Colgate Actibrush battery-operated power toothbrush. The
      single-use study, which used a single-blind, cross-over design, involved 71
      healthy subjects, who were instructed to abstain from oral hygiene for 23-25
      hours prior to brushing with each of the two toothbrushes. Plaque was measured
      using the Proximal Marginal Index (PMI) pre- and post-brushing. The 3-month
      parallel-group study involved a total of 113 subjects who had plaque (PMI),
      gingivitis and bleeding (Loe and Silness) scored at baseline and after 1 and 3
      months of product use. RESULTS: In both studies, the two toothbrushes were found
      to be safe. In the single-use study, significantly greater amounts of plaque were
      removed by the CrossAction manual toothbrush than by the Actibrush for the whole
      mouth as well as for marginal and approximal sites (P < 0.001). In the 3-month
      study, significantly greater plaque reduction was achieved with the CrossAction
      brush, the advantage being significant at 1 month for all sites except lingual
      sites (P < 0.05). At 3 months, there were consistent numerical advantages in
      favor of the CrossAction at all sites except lingual sites. Reductions in
      gingivitis were found to be similar with both toothbrushes.

PMID- 12003484
TI  - Comparison of the safety and efficacy of an oscillating/rotating battery-powered
      toothbrush and a standard manual toothbrush.
AB  - PURPOSE: To compare the cleaning efficacy of a battery-powered toothbrush with an
      oscillating/rotating action (Dr. Best Powerclean) and a standard flat-trimmed
      manual toothbrush (Elmex super 39) in a single-blind, cross-over clinical study.
      MATERIALS AND METHODS: 78 healthy subjects took part in the study. Subjects were
      asked to abstain from all oral hygiene procedures for 48 hours, after which hard
      and soft oral tissues were examined. Plaque was then scored using the Turesky
      modification of the Quigley-Hein Index, and subjects were instructed to brush
      their teeth for a total time of 1 minute with either one or the other brush,
      according to a predetermined randomization schedule. Immediately after brushing,
      plaque was scored again and hard and soft tissues were re-examined. All plaque
      scoring was carried out by the same investigator who was blind with respect to
      the brushes used. Subjects were instructed to continue with their usual oral care
      routine throughout the study period. They were scheduled to return after 12-14
      days, having again abstained from all oral hygiene for 48 hours prior to the
      visit, in order to repeat the evaluation sequence but brushing with the
      alternative brush. Prior to analysis of the results, data from the two phases of
      the study were combined. RESULTS: Both toothbrushes were found to be safe as used
      in the study. Using the non-parametric Wilcoxon test for paired samples, whole
      mouth plaque scores were found to be reduced significantly from 2.04 +/- 0.60 to
      1.57 +/- 0.51 by the Powerclean toothbrush (P < 0.001), and from 1.99 +/- 0.65 to
      1.27 +/- 0.52 by the manual toothbrush (P < 0.001). At approximal surfaces, the
      plaque scores were also significantly reduced from 2.14 +/- 0.0.59 to 1.69 +/-
      0.50 for the Powerclean (P < 0.001), and from 2.08 +/- 0.64 to 1.40 +/- 0.57 for
      the manual toothbrush (P < 0.001). A comparison of the two brushes revealed that
      the manual toothbrush removed significantly more plaque than the Powerclean, both
      for the whole mouth and approximal surfaces (P < 0.001). The Powerclean reduced
      whole mouth plaque by 23.2 +/- 11.5% compared to 37.8 +/- 14.0% for the manual
      toothbrush and approximal plaque by 20.9 +/- 10.6% and 34.9 +/- 14.0%,
      respectively. It is concluded that the Dr. Best Powerclean toothbrush is not as
      effective as a standard flat-trimmed manual toothbrush.

PMID- 12003485
TI  - A laboratory comparison of the efficacy of battery-operated, non-rechargeable
      power toothbrushes.
AB  - PURPOSE: To evaluate the cleaning efficacy of three battery-operated, non
      rechargeable, oscillating/rotating power toothbrushes, using a robot system to
      simulate normal clinical toothbrush use. MATERIALS AND METHODS: The study
      compared the cleaning efficacy of the new Braun Oral-B D4/EB4 with the Actibrush
      and the Dr. Best Powerclean in two independent experiments. Plaque substitute was
      applied to the artificial teeth of typodonts, which were cleaned by the robot
      system for a total of 2 minutes at a brushing force of 1.95 N. The remaining
      plaque substitute on buccal + lingual/palatal and occlusal surfaces, as well as
      gingival margin and interproximal sites, was measured using a computerized vision
      system. RESULTS: The new D4/EB4 was found to remove more plaque substitute than
      the Actibrush at all sites, and for all surfaces, lingual surfaces and occlusal
      surfaces the difference in favor of the D4/EB4 was statistically significant (P <
      0.05). In comparison with the Powerclean toothbrush, the D4/EB4 was significantly
      more effective at all sites (P < 0.001). These results indicate that not all
      battery-operated oscillating/rotating power toothbrushes have equal efficacy with
      respect to plaque removal and that, in this series of laboratory experiments, the
      Braun Oral-B D4/EB4 was more effective than the Actibrush and the Dr. Best
      Powerclean.

PMID- 12003486
TI  - Safety and plaque removal efficacy of a battery-operated power toothbrush and a
      manual toothbrush.
AB  - PURPOSE: To compare the safety and plaque removal efficacy of a battery-operated
      power toothbrush and a reference adult manual toothbrush. MATERIALS AND METHODS:
      This was a single-blind, randomized, split-mouth study. The power toothbrush
      studied was the Braun Oral-B Battery toothbrush (D4) and this was compared with a
      standard reference ADA manual toothbrush. The D4 toothbrush is derived from the
      Plaque Remover range of toothbrushes and has an oscillating/rotating action. At
      an initial visit, subjects (n = 48) were given a baseline examination of the oral
      hard and soft tissues and were instructed in the use of the D4. After one week
      during which subjects used the D4 at home, they returned to the test facility
      having abstained from oral hygiene for 23-25 hours. Two contralateral quadrants
      of the mouth were then randomly assigned to be cleaned with each toothbrush.
      Plaque assessments and hard and soft tissue examinations were made before and
      after brushing each quadrant for 15 seconds. Plaque was evaluated using the
      Rustogi modification of the Navy Plaque Index. RESULTS: Plaque levels were
      significantly reduced for all sites, marginal sites and approximal sites by both
      toothbrushes (P < 0.0001), but the efficacy of the D4 was significantly greater
      than that of the ADA manual brush for all comparisons (P < 0.0001). The greatest
      difference between the two toothbrushes was at approximal sites where the D4
      removed 19% more plaque than the manual toothbrush. For all sites, the D4 was 14%
      more effective, while at marginal sites the difference in favor of the D4 was
      12%.

PMID- 12003487
TI  - The poly(C)-binding proteins: a multiplicity of functions and a search for
      mechanisms.
AB  - The poly(C) binding proteins (PCBPs) are encoded at five dispersed loci in the
      mouse and human genomes. These proteins, which can be divided into two groups,
      hnRNPs K/J and the alphaCPs (alphaCP1-4), are linked by a common evolutionary
      history, a shared triple KH domain configuration, and by their poly(C) binding
      specificity. Given these conserved characteristics it is remarkable to find a
      substantial diversity in PCBP functions. The roles of these proteins in mRNA
      stabilization, translational activation, and translational silencing suggest a
      complex and diverse set of post-transcriptional control pathways. Their
      additional putative functions in transcriptional control and as structural
      components of important DNA-protein complexes further support their remarkable
      structural and functional versatility. Clearly the identification of additional
      binding targets and delineation of corresponding control mechanisms and effector
      pathways will establish highly informative models for further exploration.

PMID- 12003488
TI  - Mining biochemical information: lessons taught by the ribosome.
AB  - The publication of the crystal structures of the ribosome offers an opportunity
      to retrospectively evaluate the information content of hundreds of qualitative
      biochemical and biophysical studies of these structures. We assessed the
      correspondence between more than 2,500 experimental proximity measurements and
      the distances observed in the ribosomal crystals. Although detailed experimental
      procedures and protocols are unique in almost each analyzed paper, the data can
      be grouped into subsets with similar patterns and analyzed in an integrative
      fashion. We found that, for crosslinking, footprinting, and cleavage data, the
      corresponding distances observed in crystal structures generally did not exceed
      the maximum values expected (from the estimated length of the agent and maximal
      anticipated deviations from the conformations found in crystals). However, the
      distribution of distances had heavier tails than those typically assumed when
      building three-dimensional models, and the fraction of incompatible distances was
      greater than expected. Some of these incompatibilities can be attributed to the
      experimental methods used. In addition, the accuracy of these procedures appears
      to be sensitive to the different reactivities, flexibilities, and interactions
      among the components. These findings demonstrate the necessity of a very careful
      analysis of data used for structural modeling and consideration of all possible
      parameters that could potentially influence the quality of measurements. We
      conclude that experimental proximity measurements can provide useful distance
      information for structural modeling, but with a broad distribution of inferred
      distance ranges. We also conclude that development of automated modeling
      approaches would benefit from better annotations of experimental data for
      detection and interpretation of their significance.

PMID- 12003489
TI  - Purification and characterization of Rpp25, an RNA-binding protein subunit of
      human ribonuclease P.
AB  - In HeLa cells, ribonuclease P (RNase P), the tRNA processing enzyme consists of
      an RNA subunit (H1 RNA) associated with at least nine protein subunits, Rpp14,
      Rpp20, Rpp21, Rpp29 (hPop4), Rpp30, Rpp38, Rpp40, hPop1, and hPop5 (18.8 kDa). We
      report here the cloning and immuno-biochemical analysis of Rpp25, another protein
      subunit of RNase P. Polyclonal rabbit antibodies raised against recombinant Rpp25
      recognize their corresponding antigens in RNase P-containing fractions purified
      from HeLa cells, and they also precipitate active holoenzyme. Furthermore, this
      protein has general RNA binding properties.

PMID- 12003490
TI  - Archaeal RNase P has multiple protein subunits homologous to eukaryotic nuclear
      RNase P proteins.
AB  - Although archaeal RNase P RNAs are similar in both sequence and structure to
      those of Bacteria rather than eukaryotes, and heterologous reconstitution between
      the Bacillus subtilis RNase P protein and some archaeal RNase P RNAs has been
      demonstrated, no archaeal protein sequences with similarity to any known
      bacterial RNase P protein subunit have been identified, and the density of
      Methanothermobacter thermoautotrophicus RNase P in Cs2SO4 (1.42 g/mL) is
      inconsistent with a single small bacterial-like protein subunit. Four
      hypothetical open reading frames (MTH11, MTH687, MTH688, and MTH1618) were
      identified in the genome of M. thermoautotrophicus that have sequence similarity
      to four of the nine Saccharomyces cerevisiae RNase P protein subunits: Pop4p,
      Pop5p, Rpp1p, and Rpr2p, respectively. Polyclonal antisera generated to
      recombinant Mth11p, Mth687p, Mth688p, and Mth1618p each recognized a protein of
      the predicted molecular weight in western blots of partially purified M.
      thermoautotrophicus RNase P, and immunoprecipitated RNase P activity from the
      same partially purified preparation. RNase P in Archaea is therefore composed of
      an RNA subunit similar to bacterial RNase P RNA and multiple protein subunits
      similar to those in the eukaryotic nucleus.

PMID- 12003491
TI  - Effects of magnesium ions on the stabilization of RNA oligomers of defined
      structures.
AB  - Optical melting was used to determine the stabilities of 11 small RNA oligomers
      of defined secondary structure as a function of magnesium ion concentration. The
      oligomers included helices composed of Watson-Crick base pairs, GA tandem base
      pairs, GU tandem base pairs, and loop E motifs (both eubacterial and eukaryotic).
      The effect of magnesium ion concentration on stability was interpreted in terms
      of two simple models. The first assumes an uptake of metal ion upon duplex
      formation. The second assumes nonspecific electrostatic attraction of metal ions
      to the RNA oligomer. For all oligomers, except the eubacterial loop E, the data
      could best be interpreted as nonspecific binding of metal ions to the RNAs. The
      effect of magnesium ions on the stability of the eubacterial loop E was distinct
      from that seen with the other oligomers in two ways. First, the extent of
      stabilization by magnesium ions (as measured by either change in melting
      temperature or free energy) was three times greater than that observed for the
      other helical oligomers. Second, the presence of magnesium ions produces a
      doubling of the enthalpy for the melting transition. These results indicate that
      magnesium ion stabilizes the eubacterial loop E sequence by chelating the RNA
      specifically. Further, these results on a rather small system shed light on the
      large enthalpy changes observed upon thermal unfolding of large RNAs like group I
      introns. It is suggested that parts of those large enthalpy changes observed in
      the folding of RNAs may be assigned to variations in the hydration states and
      types of coordinating atoms in some specifically bound magnesium ions and to an
      increase in the observed cooperativity of the folding transition due to the
      binding of those magnesium ions coupling the two stems together. Brownian dynamic
      simulations, carried out to visualize the metal ion binding sites, reveal rather
      delocalized ionic densities in all oligomers, except for the eubacterial loop E,
      in which precisely located ion densities were previously calculated.

PMID- 12003492
TI  - Dual function of the tRNA(m(5)U54)methyltransferase in tRNA maturation.
AB  - A 5-methyluridine (m(5)U) residue at position 54 is a conserved feature of
      bacterial and eukaryotic tRNAs. The methylation of U54 is catalyzed by the
      tRNA(m5U54)methyltransferase, which in Saccharomyces cerevisiae is encoded by the
      nonessential TRM2 gene. In this study, we identified four different strains with
      mutant forms of tRNA(Ser)CGA. The absence of the TRM2 gene in these strains
      decreased the stability of tRNA(Ser)CGA and induced lethality. Two alleles of
      TRM2 encoding catalytically inactive tRNA(m5U54)methyltransferases were able to
      stabilize tRNA(Ser)CGA in one of the mutants, revealing a role for the Trm2
      protein per se in tRNA maturation. Other tRNA modification enzymes interacting
      with tRNA(Ser)CGA in the maturation process, such as Pus4p, Trm1 p, and Trm3p
      were essential or important for growth of the tRNA(Ser)CGA mutants. Moreover,
      Lhp1p, a protein binding RNA polymerase III transcripts, was required to
      stabilize the mutant tRNAs. Based on our results, we suggest that tRNA
      modification enzymes might have a role in tRNA maturation not necessarily linked
      to their known catalytic activity.

PMID- 12003493
TI  - Replacement of the yeast TRP4 3' untranslated region by a hammerhead ribozyme
      results in a stable and efficiently exported mRNA that lacks a poly(A) tail.
AB  - The mRNA poly(A) tail serves different purposes, including the facilitation of
      nuclear export, mRNA stabilization, efficient translation, and, finally, specific
      degradation. The posttranscriptional addition of a poly(A) tail depends on
      sequence motifs in the 3' untranslated region (3' UTR) of the mRNA and a complex
      trans-acting protein machinery. In this study, we have replaced the 3' UTR of the
      yeast TRP4 gene with sequences encoding a hammerhead ribozyme that efficiently
      cleaves itself in vivo. Expression of the TRP4-ribozyme allele resulted in the
      accumulation of a nonpolyadenylated mRNA. Cells expressing the TRP4-ribozyme mRNA
      showed a reduced growth rate due to a reduction in Trp4p enzyme activity. The
      reduction in enzyme activity was not caused by inefficient mRNA export from the
      nucleus or mRNA destabilization. Rather, analyses of mRNA association with
      polyribosomes indicate that translation of the ribozyme-containing mRNA is
      impaired. This translational defect allows sufficient synthesis of Trp4p to
      support growth of trp4 cells, but is, nevertheless, of such magnitude as to
      activate the general control network of amino acid biosynthesis.

PMID- 12003494
TI  - An element in the 3' untranslated region of human LINE-1 retrotransposon mRNA
      binds NXF1(TAP) and can function as a nuclear export element.
AB  - Export of unspliced mRNA to the cytoplasm is required for the replication of all
      retroviruses. In simian type D retroviruses, the RNA export is mediated by the
      constitutive transport element (CTE) that binds the cellular nuclear export
      factor 1, NXF1(TAP). To search for potential cellular RNA substrates for NXF1, we
      have set up an in vitro selection procedure, using an RNA library expressed from
      total human genomic DNA. A sequence that was isolated most frequently as
      independent clones exhibits extensive homology to the 3' untranslated region of
      expressed LINE1 (L1) retrotransposons. This region, termed L1-NXF1 binding
      element (L1-NBE) bears no structural resemblance to the viral CTE, but binds NXF1
      as strongly as CTE, based on gel mobility shift competition assays. A deletion
      analysis of the NXF1 protein reveals that CTE and L1-NBE have different, but
      overlapping, binding domains on NXF1. Placed in an intron, L1-NBE is capable of
      mediating nuclear export of lariat RNA species in Xenopus laevis oocytes and of
      an unspliced HIV-1 derived RNA in human 293 cells, suggesting that it may
      function as a nuclear export element for the intronless L1 mRNA.

PMID- 12003495
TI  - Switching the in vitro tRNA usage of HIV-1 by simultaneous adaptation of the PBS
      and PAS.
AB  - Reverse transcription of the HIV-1 RNA genome is primed by the cellular
      tRNA(lys3) molecule that anneals to a complementary sequence in the viral genome,
      the primer-binding site (PBS). Additional interactions between the tRNA primer
      and the viral RNA were proposed to play a role in reverse transcription. We
      recently identified an 8-nt element in the U5 region upstream of the PBS that is
      critical for initiation and processive elongation of reverse transcription. This
      motif was termed the primer activation signal (PAS), and is proposed to interact
      with the "antiPAS sequence" in the TphiC arm of tRNA(lys3). In this study, we
      demonstrate that the efficiency of initiation of reverse transcription can be
      modulated by PAS mutations that strengthen or weaken the interaction with
      antiPAS. These results provide further evidence for a direct base-pairing
      interaction between the PAS in the viral RNA and the antiPAS in the tRNA(lys3)
      molecule. A broad phylogenetic survey indicated that a PAS element is present in
      all retroviral RNA genomes, suggesting that the process of reverse transcription
      is regulated by a common mechanism in all retroviridae. It has proven very
      difficult to change the identity of the tRNA primer for HIV-1 reverse
      transcription by changing the PBS sequence. Using in vitro reverse transcription
      assays, we demonstrate that the identity of the priming tRNA species can be
      switched by simultaneous alteration of the PBS and PAS motifs to accommodate a
      new tRNA primer. These results indicate that the PAS-antiPAS interaction is
      important for both primer selection and efficient reverse transcription.

PMID- 12003496
TI  - A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine
      modification of tRNA.
AB  - Dihydrouridine modification of tRNA is widely observed in prokaryotes and
      eukaryotes, as well as in some archaea. In Saccharomyces cerevisiae every
      sequenced tRNA has at least one such modification, and all but one have two or
      more. We have used a biochemical genomics approach to identify the gene encoding
      dihydrouridine synthase 1 (Dus1, ORF YML080w), using yeast pre-tRNA(Phe) as a
      substrate. Dus1 is a member of a widespread family of conserved proteins, three
      other members of which are found in yeast: YNR015w, YLR405w, and YLR401c. We show
      that one of these proteins, Dus2, encoded by ORF YNR015w, has activity with two
      other substrates: yeast pre-tRNA(Tyr) and pre-tRNA(Leu). Both Dus1 and Dus2 are
      active as a single subunit protein expressed and purified from Escherichia coli,
      and the activity of both is stimulated in the presence of flavin adenine
      dinucleotide. Dus1 modifies yeast pre-tRNA(Phe) in vitro at U17, one of the two
      positions that are known to bear this modification in vivo. Yeast extract from a
      dus1-A strain is completely defective in modification of yeast pre-tRNAPhe, and
      RNA isolated from dus1-delta and dus2-delta strains is significantly depleted in
      dihydrouridine content.

PMID- 12003497
TI  - Successful aging among the young-old, old-old, and oldest-old Chinese.
AB  - In this study, successful aging was defined by four dimensions including
      functional status, affective status, cognitive status, and productive involvement
      status. This study examined successful aging among Hong Kong Chinese old people
      in three different age cohorts: young-old, old-old, and oldest-old. The
      respondents were 1106 people aged 60 years or older from a cross-sectional study
      of a representative community sample of the elderly population in Hong Kong. We
      found modest associations between four dimensions of successful aging, indicating
      the relative independence of these four criteria for successful aging. Using
      multiple regression models, we found that age, gender, years of education, number
      of close relatives, frequency of contact with friends, financial strain, number
      of chronic illnesses, self-rated health, hearing impairment, and life
      satisfaction were associated with the successful aging indicator.

PMID- 12003498
TI  - Trends in financial satisfaction: does poverty make a difference?
AB  - Gerontological studies on financial satisfaction have been limited by the dearth
      of longitudinal research and the lack of research that includes the concept of
      poverty. In order to bridge these gaps, this longitudinal study examines and
      compares the intracohort and intercohort effects on financial satisfaction trends
      by poverty status among Americans age 45 and above, using data from the General
      Social Surveys. The results suggest that for both the poor and the non-poor,
      changes in financial satisfaction trends are mostly due to strong negative
      intercohort effects, indicating that younger cohorts are less satisfied
      financially than the older ones. There appears to be a significant difference in
      the intercohort effects of financial satisfaction trends between the poor and the
      non-poor. However, such difference can be accounted for by the differences in the
      effects of education and social comparison (or relative deprivation) on financial
      satisfaction between the poor and the non-poor.

PMID- 12003499
TI  - Older women's development: a comparison of women in their 60s and 80s on a
      measure of Erikson's developmental tasks.
AB  - This study compared older women from two age groups in order to refine and extend
      our understanding of women's development across the life span. Forty-one women
      from two cohorts aged 60 to 70 and 80 to 90 completed the Measures of
      Psychosocial Development (MPD), a quantitative measure of Erikson's developmental
      stages. Age group differences in the resolution of Erikson's identity and trust
      developmental tasks were found. In addition, these two groups differed on the
      three summary scales: totals across the positive subscales, negative subscales,
      and resolution subscales respectively. Implications for women's late life
      development and possible interventions are discussed.

PMID- 12003500
TI  - Grandparents in law: investigating the institutionalization of extended family
      roles.
AB  - Previous research on grandparents has focused on the individual and familial
      level and has characterized grandparent roles as ambiguous and contingent.
      Emphasizing instead structural phenomena, this theoretical paper argues that
      grandmother and grandfather roles are being institutionalized through state and
      federal legislation. This phenomenon provides an opportunity to investigate the
      process of institutionalization as it happens. Grandparenthood is evaluated as a
      potential site for institutionalization and law as a source of
      institutionalization is discussed. Preliminary evidence of the legal
      institutionalization of grandparenthood is presented and implications and
      directions for further research are suggested.

PMID- 12003501
TI  - "There's no place like home": an analysis of young adults' mature coresidency in
      Canada.
AB  - This article investigates the propensity for young adults to live in the parental
      home between the ages of 25 to 34--termed "mature coresidency." Drawing upon a
      synthesis of life course theory and the concept of social capital, a rationale is
      developed for examination of emotional closeness to parents during childhood and
      a number of socio-demographic and structural factors deemed to be important.
      Using a subset of young adults aged 25 to 34 (N = 1,760) from the 1995 Canadian
      General Social Survey, it is found that emotional closeness to mothers and
      fathers are major determinants of mature coresidency. Other important predictors
      include child's age, gender, marital status, and several family background
      factors. The implications of the findings are discussed for transitions to
      adulthood and family development against a changing social and economic
      landscape.

PMID- 12003502
TI  - Girls' identity dilemmas: spaces defined by definitions of worth.
AB  - Many of the models and metaphors that underlie research on eating disorders
      reflect a modernist version of the self and, quite often, one that was developed
      in the early 1900s. Psychoanalytic theories persist despite new "postmodern"
      theories of the self that challenge these older theories by paying close
      attention to the processes of self-creation in relation to culture or discourse.
      I suggest using newer theories of the self in research and practice so that
      health care professionals may increase their understanding of how identities are
      formed in postmodern societies. In particular, I discuss how health professionals
      can work with adolescent girls to address the phenomenon of eating disorders and
      related health concerns. Whether one-to-one, in groups, in schools, or other
      settings, the strategies suggested can be used by nurses, educators, counselors,
      child and youth care workers, and psychologists.

PMID- 12003503
TI  - "They don't trust us; we're just kids:" views about community from predominantly
      female inner city youth.
AB  - The cornerstones of health promotion are the concepts of empowerment and
      community participation. There has been little research, however, on how these
      concepts are actualized within a youth population and even less from a gender
      perspective. Girls are socialized to be more compliant and cooperative; thus they
      feel less assertive to express themselves. The benefits of community
      participation, such as the development of personal identity and increased self
      determination, may therefore be more important for girls' development. In this
      qualitative study I explored youth's perceptions about community, their ability
      to be heard, and their power to effect community change. Responses to focus
      groups and an on-line sentence completion exercise by 23 well-functioning,
      predominantly female (83%) youth, at an inner-city school in Canada, revealed
      that youth perceived that they were not heard and felt disempowered in the larger
      community. Three subthemes explain these threats to empowerment: "grown-ups run
      everything" (they had no actual decision-making power), "we're just kids" (they
      were low in the social hierarchy), and "they don't trust us" (they felt mutual
      mistrust of and by adults). Boys showed some evidence of feeling more empowered
      than girls. Boys and girls identified that they perceived they could make a
      difference, particularly in their school. Five themes of empowerment help to
      explain this perception, including, "adults who know us, trust us" (they were
      trusted by some adults), in school "they ask us what should we do" (they had some
      participation in decision making), "we can make a difference" (they felt self
      efficacy), "we can do it as a group" (they had a belief in group action), and
      they could "get someone big so they would listen" (they demonstrated political
      efficacy). Implications for community health practitioners are discussed.

PMID- 12003504
TI  - Data collection strategies for accessing adolescent women's worlds.
AB  - A two-year study was initiated in 1999 to investigate adolescent women's health
      concerns pertaining to their relationships. Data were obtained from four groups
      of girls (ages 14-19; N = 31) that met for approximately 18 weeks each. To help
      equalize power in the groups and facilitate a respectful and caring environment,
      we encouraged each group to use a variety of strategies, including those based on
      feminist principles. Data collection procedures based on feminist values can
      enable researchers to gain rich descriptions on the lived experience of
      adolescent women. Such procedures can help create an environment in which
      individuals can articulate their concerns and collectively co-construct the
      meanings of life events in health-promoting and consciousness-raising ways.

PMID- 12003505
TI  - Cigarette smoking and the disenfranchisement of adolescent girls: a discourse of
      resistance?
AB  - The consequences of smoking for women are of particular concern in light of
      recent observations that more adolescent females than males are taking up
      smoking. To date, few studies have explored gender differences in depth, but we
      do know that males and females smoke for different reasons and that current
      smoking prevention programs may be differentially effective depending on gender.
      Recent evidence suggests that the school environment may have an important
      influence on smoking. The purpose of this study, therefore, was to explore gender
      differences in the relationships between cigarette smoking and adolescents'
      experiences of school climate and their relationships with the school and
      significant adults in their lives. A secondary data analysis was done using a
      data set derived from a student survey conducted in 20 secondary schools in
      British Columbia (BC), Canada, which included 8,179 students in grades 8 to 12.
      Analyses were primarily descriptive. The results demonstrated that adolescent
      girls who smoke are more likely than either males or nonsmoking females to
      experience powerlessness in their school environment and to feel considerably
      less attachment to the school. Female smokers are more likely than males or
      female nonsmokers to be engaged in oppositional, distanced, and unsatisfactory
      relationships with important adults in their lives, particularly those who are in
      positions of relative power and authority. These findings are discussed in
      relation to critical and feminist perspectives that suggest smoking is part of a
      larger discourse of resistance within schools. The implications for health
      practitioners are discussed.

PMID- 12003506
TI  - Adolescent behavior and sexually transmitted diseases: the dilemma of human
      papillomavirus.
AB  - Adolescence is a period of physical, cognitive, psychosocial, and moral
      development that often results in risk-taking behavior. As a consequence,
      adolescents are at high risk for sexually transmitted disease (STD). Two of the
      most common STDs in the United States, chlamydia and human papillomavirus (HPV),
      affect millions of adolescent women. HPV, contrasted with chlamydia, poses a
      unique challenge to health care providers. In addition to causing genital warts,
      HPV has been shown to be the causative agent in the development of cervical
      cancer. Interventions that are effective in decreasing the transmission of
      chlamydia, such as increasing condom use, are less effective in prevention of
      HPV. Efforts to increase adolescent awareness of HPV, to increase age of first
      coitus, and to decrease numbers of sexual partners are more effective for HPV
      prevention. Early screening for HPV, smoking cessation, and health promotion may
      be effective in decreasing the incidence of cervical cancer in young women. Nurse
      practitioners and other primary health care providers need a more holistic
      approach to the prevention of HPV in adolescent women.

PMID- 12003507
TI  - Final consonant discrimination in children: effects of phonological disorder,
      vocabulary size, and articulatory accuracy.
AB  - Preschool-age children with phonological disorders were compared to their
      typically developing age peers on their ability to discriminate CVC words that
      differed only in the identity of the final consonant in whole-word and gated
      conditions. The performance of three age groups of typically developing children
      and adults was also assessed on the same task. Children with phonological
      disorders performed more poorly than age-matched peers, and younger typically
      developing children performed more poorly than older children and adults, even
      when the entire CVC word was presented. Performance in the whole-word condition
      was correlated with receptive vocabulary size and a measure of articulatory
      accuracy across all children. These results suggest that there is a complex
      relationship among word learning skills, the ability to attend to fine phonetic
      detail, and the acquisition of articulatory-acoustic and acoustic-auditory
      representations.

PMID- 12003508
TI  - Statistical power in stuttering research: a tutorial.
AB  - The capacity to make reliable inductive statements about populations is critical
      for the advancement of scientific knowledge. An important contribution to that
      advancement of knowledge is determining that effects are either present or not
      present in populations. Statistical power is an important methodological
      qualification for any research that presents statistical results, and
      particularly so for research that presents null results. In this paper we
      describe the statistical concept of power, outline parameters of research that
      influence it, and demonstrate how it is calculated. With reference to selected
      published research, attention is drawn to the problems associated with a body of
      underpowered research, one being that population effects may go undetected. One
      way to prevent this problem is to calculate power a priori in planning research
      and include confidence intervals when presenting the results of research.
      However, it is difficult, if not impossible in many cases, to obtain high
      participant numbers for communication disorders of low prevalence such as
      stuttering. With this in mind, the paper concludes with an attempt to open
      discussion about ways to redress the problems associated with statistical power.

PMID- 12003509
TI  - Phonological progress during the first 2 years of stuttering.
AB  - This report is the third in a series on phonological impairment in children who
      stutter, comparing its extent in those whose stuttering will be persistent with
      those in whom that disorder will disappear spontaneously. The first (E. P. Paden
      & E. Yairi, 1996) compared small groups of these children with normally fluent
      children of the same ages and sex. The second (E. P. Paden, E. Yairi, & N. G.
      Ambrose, 1999) compared the phonological abilities evidenced soon after onset of
      stuttering for 84 young children. In that study, the mean level of phonological
      skills of the 22 participants whose stuttering eventually persisted for at least
      4 years was found to be significantly poorer than that of 62 others whose
      stuttering would disappear without fluency intervention before that time. In the
      present study, recorded performances of the same 84 children, made 1 and 2 years
      later, were similarly evaluated to determine how their phonological development
      progressed after the initial visit. Results of assessment at the 1-year visit
      showed that the mean difference between the two groups of children was no longer
      significant. The children whose stuttering would persist had improved more
      phonologically than had those who would recover from stuttering. At the 2-year
      visit, the mean percentage of phonological error for the two groups was
      identical. Furthermore, at this assessment, only 3 of the children in the
      Persistent group and 11 of those in the Recovered group had not essentially
      mastered all of the 10 basic patterns of phonology that were the focus of our
      evaluation. The findings concerning the longitudinal covariance of stuttering and
      phonological skills provide information that should be considered in any attempt
      to explain the relation between the two.

PMID- 12003510
TI  - Biological mechanisms underlying voice changes due to dehydration.
AB  - Four vocally untrained healthy adults, 2 men and 2 women, completed the study. A
      double-blind placebo-controlled approach was used to administer three treatments
      to each participant on separate days. Drugs treatments involved a single 60-mg
      dose of a diuretic, Lasix (LA), on one day, and a single 50-mg dose of an oral
      antihistamine, diphenhydramine hydrochloride (DH), on another day. A third day
      involved the administration of a placebo, sugar pills (SP). Critical
      posttreatment measures were weight (kg), which estimated systemic dehydration,
      saliva viscosity (centipoise), which estimated secretion dehydration, and
      phonation threshold pressure (PTP, in cm H2O), at high pitches, which indicated
      pulmonary drive for phonation. The central experimental question was: Does
      systemic dehydration, or secretory dehydration, or both, mediate increases in PTP
      that are known to occur following dehydration treatments? The results showed that
      LA induced systemic dehydration, as shown by a decrease in total body mass of
      about 1%. Weight losses were seen during a 1- to 4-hour block following drug
      administration and persisted for at least 8 hours thereafter. PTPs also increased
      in that condition, about 23% relative to baseline, but only several hours after
      whole-body dehydration was initially seen (5-12 hours after drug administration).
      In contrast, no evidence was seen that DH accomplished either secretory
      dehydration or PTP shifts. The results indicate that systemic dehydration can
      mediate PTP increases. The influence of secretory dehydration on PTP is unclear.

PMID- 12003511
TI  - Acoustic cues to the voicing feature in tracheoesophageal speech.
AB  - Tracheoesophageal (TE) speakers often have difficulty producing the
      voiced/voiceless distinction. This limitation has been attributed to use of the
      pharyngoesophageal segment as the phonatory source. The nature of this tissue may
      preclude precise control of voicing onset, a contributing cue to a phoneme's
      voicing feature, at least in laryngeal speech. The purpose of this study was to
      determine whether voiced and voiceless consonants produced by TE speakers could
      be differentiated from those produced by laryngeal speakers using four acoustic
      measures associated with the voicing characteristic of consonants in laryngeal
      speech. Sixteen TE and ten laryngeal speakers produced five stop and fricative
      cognate pairs embedded in a carrier phrase. Three of the four acoustic measures
      contributed significantly to the discriminant models that differentiated
      accurately perceived TE and laryngeal samples. The three variables were consonant
      sound pressure level, consonant duration, and preceding vowel duration. In
      general, values for each measure were higher/longer for the TE group. The
      discriminant functions were interpreted as a reflection of TE speaker attempts at
      overarticulation.

PMID- 12003512
TI  - Sensorimotor adaptation of speech I: Compensation and adaptation.
AB  - When motor actions (e.g., reaching with your hand) adapt to altered sensory
      feedback (e.g., viewing a shifted image of your hand through a prism), the
      phenomenon is called sensorimotor adaptation (SA). In the study reported here, SA
      was observed in speech. In two 2-hour experiments (adaptation and control),
      participants whispered a variety of CVC words. For those words containing the
      vowel /E/, participants heard auditory feedback of their whispering. A DSP-based
      vocoder processed the participants' auditory feedback in real time, allowing the
      formant frequencies of participants' auditory speech feedback to be shifted. In
      the adaptation experiment, formants were shifted along one edge of the vowel
      triangle. For half the participants, formants were shifted so participants heard
      /a/ when they produced /E/; for the other half, the shift made participants hear
      /i/ when they produced /E/. During the adaptation experiment, participants
      altered their production of /E/ to compensate for the altered feedback, and these
      production changes were retained when participants whispered with auditory
      feedback blocked by masking noise. In a control experiment, in which the formants
      were not shifted, participants' production changes were small and inconsistent.
      Participants exhibited a range of adaptations in response to the altered
      feedback, with some participants adapting almost completely, and other
      participants showing very little or no adaptation.

PMID- 12003513
TI  - Acoustic patterns of infant vocalizations expressing emotions and communicative
      functions.
AB  - The present study aimed at identifying the acoustic pattern of vocalizations,
      produced by 7- to 11-month-old infants, that were interpreted by their mothers as
      expressing emotions or communicative functions. Participants were 6 healthy,
      first-born English infants, 3 boys and 3 girls, and their mothers. The acoustic
      analysis of the vocalizations was performed using a pattern recognition (PR)
      software system. A PR system not only calculates signal features, it also
      automatically detects patterns in the arrangement of such features. The following
      results were obtained: (a) the PR system distinguished vocalizations interpreted
      as emotions from vocalizations interpreted as communicative functions with an
      overall accuracy of 87.34%; (b) the classification accuracy of the PR system for
      vocalizations that convey emotions was 85.4% and for vocalizations that convey
      communicative functions was 89.5%; and (c) compared to vocalizations that express
      emotions, vocalizations that express communicative functions were shorter,
      displayed lower fundamental frequency values, and had greater overall intensity.
      These findings suggest that in the second half of the first year, infants possess
      a vocal repertoire that contributes to regulating cooperative interaction with
      their mothers, which is considered one of the major prerequisites for language
      acquisition.

PMID- 12003514
TI  - Narrative discourse in young children with histories of early corrective heart
      surgery.
AB  - Narrative attainment was assessed in a group of 76 four-year-old children at risk
      for brain injury because of histories of early corrective heart surgery. Elicited
      personal experience narratives were coded for narrative components, evaluative
      devices, and information adequacy and were contrasted with narratives produced by
      a comparison group of typically developing 4-year-olds. The production of
      autonomous narrative discourse was identified as an area of special vulnerability
      for children with this medical history. Despite considerable heterogeneity in
      narrative performance, children with early corrective heart surgery produced
      fewer narrative components than typically developing children. Results suggest
      that the elaboration of events and contextual information, the expression of
      subjective evaluation and causality, and clarity and explicitness of information
      reporting may constitute special challenges for this population of children.
      Implications of these findings for clinical assessment and possible risks for
      socioemotional relationships and academic achievement are discussed.

PMID- 12003515
TI  - Semantic representation and naming in young children.
AB  - Children's semantic representations and semantic naming errors were the focus of
      this study. In Experiment 1, 25 normally developing children (mean age = 5 years
      4 months) named, drew, and defined 20 age-appropriate objects. The results
      suggested that functional and physical properties are core aspects of object
      representations in the semantic lexicon and that these representations are often
      organized and accessed according to a taxonomic hierarchy. Results of a new
      procedure, comparative picture naming/picture drawing, suggested that the degree
      of knowledge in the semantic lexicon makes words more or less vulnerable to
      retrieval failure. Most semantic naming errors were associated with limited
      semantic knowledge, manifested as either lexical gaps or fragile representations.
      Comparison of definitions for correctly named and semantically misnamed objects
      provided converging evidence for this conclusion. In Experiment 2, involving 16
      normally developing children (mean age = 5 years 5 months), the comparative
      picture naming/picture drawing results were replicated with a stimulus set that
      allowed a priori matching of the visual complexity of items drawn from correct
      and semantic error pools. Discussion focuses on the dynamic nature of semantic
      representations and the relation between semantic representation and naming
      during a period of slow mapping. The value of comparative picture naming/picture
      drawing as a new method for exploring children's semantic representations is
      emphasized.

PMID- 12003516
TI  - Balancing bilinguals II: lexical comprehension and cognitive processing in
      children learning Spanish and English.
AB  - The present study investigated developmental changes in lexical comprehension
      skills in early sequential bilinguals, in both Spanish (L1) and English (L2),
      exploring the effects of age, years of experience, and basic-level cognitive
      processing (specifically the ability to maintain performance during mixed vs.
      single-language processing) within a timed picture-word verification task.
      Participants were 100 individuals, 20 at each of five different age levels (ages
      in years, 5-7, 8-10, 11-13, 14-16, and adults). All had learned Spanish as a
      first language in the home, with formal English experience beginning at 5 years.
      Gains (as indexed by increased response speed) were made in both languages across
      age, although these gains were greater in English than in Spanish. The youngest
      participants were relatively "balanced" in their crosslinguistic performance. By
      middle childhood, performance was better in English. There were no response
      decrements at any age between the mixed and single-language processing
      conditions. These results are compared to those from a previous study that
      investigated basic-level lexical production in developing Spanish-English
      bilinguals. Both studies show a move toward English dominance in middle
      childhood, but the transition occurs earlier in comprehension. The production
      study showed differences between mixed and single-language processing (reflecting
      potential interlanguage interference) that are not evident in comprehension.

PMID- 12003517
TI  - Language and reading outcomes to age 9 in late-talking toddlers.
AB  - Language and reading outcomes at 6 to 9 years of age were examined in a sample of
      34 children who were late talkers as toddlers. The late talkers, who all had
      normal nonverbal ability and age-adequate receptive language at intake, were
      compared to a group of 25 typically developing children matched at intake (24 to
      31 months) on age, socioeconomic status, and nonverbal ability. Late talkers
      performed in the average range on most language tasks by age 5. However, they had
      significantly poorer scores on most language measures through age 9. The groups
      did not differ in reading skills at age 6 or 7, but the late talkers were
      slightly less skilled in reading at ages 8 and 9. Findings suggest that slow
      early language development reflects a predisposition for slower acquisition and
      lower asymptotic performance in a wide range of language-related skills into
      middle childhood.

PMID- 12003518
TI  - Adults' judgments of fictional story quality.
AB  - Narratives are commonly used for research and clinical purposes, but the
      ecological validity of our analyses needs verification. Do our macrostructural
      and microstructural narrative analysis methods give us an accurate picture of
      what would generally be considered "story quality"? We addressed this question by
      using 39 untrained adult judges who were presented with sets of brief stories,
      each set constructed to vary on a single story aspect (story grammar elements,
      story grammar structural pattern, referring expressions, or connectives). Judges
      ranked the stories in each set from best to worst. Results indicate that judges
      were generally sensitive to story features commonly used in narrative analyses,
      including characters' thoughts and feelings, goal-directedness, adequacy of
      referent introductions, and connectedness of clauses. However, they failed to
      make distinctions between stories that differed in types of connectives or
      referring expressions and had mixed reactions to description in stories.

PMID- 12003519
TI  - Judgments of idiom familiarity and transparency: a comparison of children and
      adolescents.
AB  - Idioms (e.g., go by the book, keep a straight face) are figurative expressions
      that frequently occur in the English language. Given the pervasiveness of these
      expressions, it is important that young people can understand their meanings.
      Developmental studies have shown that idioms that are higher in familiarity and
      transparency (e.g., blow off some steam) are generally easier for children and
      adolescents to understand than those that are less familiar and more opaque
      (e.g., pull up one's socks). In those studies, judgments of idiom familiarity and
      transparency were based on the perceptions of individuals who were older than the
      study participants. In the present study, 11-year-old children (n = 50) and 16
      year-old adolescents (n = 50) were asked to judge the familiarity and
      transparency of a set of 20 idioms. Their comprehension of the same expressions
      was also examined. The results indicated that the children were less familiar
      with the idioms and had greater difficulty comprehending them than did the
      adolescents. However, the children's transparency judgments did not differ from
      those of the adolescents. For the children, the easiest idioms were also more
      familiar and transparent than the most difficult expressions. For the
      adolescents, the easiest idioms were more transparent than the most difficult
      ones, but the two types did not differ in familiarity. Suggestions are offered
      for conducting future studies of the development of idiom understanding in youth.

PMID- 12003520
TI  - Modulation detection interference in listeners with normal and impaired hearing.
AB  - Listeners were asked to detect amplitude modulation (AM) of a target (or signal)
      carrier that was presented in isolation or in the presence of an additional
      (masker) carrier. The signal was modulated at a rate of 10 Hz, and the masker was
      unmodulated or was modulated at a rate of 2, 10, or 40 Hz. Nine listeners had
      normal hearing, 4 had a bilateral hearing loss, and 4 had a unilateral hearing
      loss; those with a unilateral loss were tested in both ears. The listeners with a
      hearing loss had normal hearing at 1 kHz and a 30- to 40-dB loss at 4 kHz. The
      carrier frequencies were 984 and 3952 Hz. In one set of conditions, the lower
      frequency carrier was the signal and the higher frequency carrier was the masker.
      In the other set, the reverse was true. For the impaired ears, the carriers were
      presented at 70 dB SPL. For the normal ears, either the carriers were both
      presented at 70 dB SPL or the higher frequency carrier was reduced to 40 dB SPL
      to simulate the lower sensation level experienced by the impaired ears. There was
      considerable individual variability in the results, and there was no clear effect
      of hearing loss. These results suggest that a mild, presumably cochlear hearing
      loss does not affect the ability to process AM in one frequency region in the
      presence of competing AM from another region.

PMID- 12003521
TI  - Visual attention in children with normal hearing, children with hearing aids, and
      children with cochlear implants.
AB  - Previous studies have reported both positive and negative effects of deafness on
      visual attention. The purpose of this study was to replicate and expand findings
      of previous studies by examining visual attention abilities in children with
      deafness and children with normal hearing. Twenty-eight children, ages 8-14
      years, were evaluated. There were two groups of children with prelingual deafness
      and one group with normal hearing. The children with deafness were divided
      further into two groups: those with cochlear implants and those with conventional
      hearing aids. Unlike previous studies, the current study found no substantial
      differences in performance among these three groups of children on a continuous
      performance visual attention task or on a letter cancellation task. Children in
      all three groups performed very well on the visual attention tasks. Furthermore,
      there was little association between performance on the visual attention tasks
      and parent or teacher ratings of behavior and attention. Age and nonverbal
      intelligence were significantly correlated with performance on visual attention
      tasks. The theoretical implications of these findings are discussed, along with
      directions for future research.

PMID- 12003522
TI  - Synthesis and evaluation of keto-glutamine analogues as inhibitors of hepatitis A
      virus 3C proteinase.
AB  - Hepatitis A virus (HAV) 3C enzyme is a picornaviral cysteine proteinase involved
      in the processing of the initially synthesized viral polyprotein and is therefore
      important for viral maturation and infectivity. Although it is a cysteine
      proteinase, this enzyme has a topology similar to those of the chymotrypsin-like
      serine proteinases. Since the enzyme recognizes peptide substrates with a
      glutamine residue at the P(1) site, a number of ketone-containing glutamine
      compounds analogous to nanomolar inhibitors of cathepsin K were synthesized and
      tested for inhibition against HAV 3C proteinase. In addition, a 3-azetidinone
      scaffold was incorporated into the glutamine fragment but gave only modest
      inhibition. However, introduction of a phthalhydrazido group alpha to the ketone
      moiety gave significantly better inhibitors with IC(50) values ranging from 13 to
      164 microM, presumably due to the effect of intramolecular hydrogen bonding to
      the ketone. In addition, the tetrapeptide phthalhydrazide 24 was found to be a
      competitive reversible inhibitor (K(i) = 9 x 10(-6) M) and also showed no loss of
      inhibitory potency in the presence of dithiothreitol.

PMID- 12003523
TI  - Intramolecular general base catalyzed ester hydrolysis. The hydrolysis of 2
      aminobenzoate esters.
AB  - Rate constants have been obtained for the hydrolysis of the trifluoroethyl,
      phenyl, and p-nitrophenyl esters of 2-aminobenzoic acid at 50 degrees C in H(2)O.
      The pseudo-first-order rate constants, k(obsd), are pH independent from pH 8 to
      pH 4 (the pK(a) of the amine group conjugate acid). The 2-aminobenzoate esters
      hydrolyze with similar rate constants in the pH-independent reactions, and these
      water reactions are approximately 2-fold slower in D(2)O than in H(2)O. The most
      likely mechanism involves intramolecular general base catalysis by the
      neighboring amine group. The rate enhancements in the pH-independent reaction in
      comparison with the pH-independent hydrolysis of the corresponding para
      substituted esters or the benzoate esters are 50-100-fold. In comparison with the
      hydroxide ion catalyzed reaction, the enhancement in k(obsd) at pH 4 with the
      phenyl ester is 10(5)-fold. Intramolecular general base catalyzed reactions are
      assessed in respect to their relative advantages and disadvantages in enzyme
      catalysis. A general base catalyzed reaction can be more rapid at low pH than a
      nucleophilic reaction that has a marked dependence on pH and the leaving group.

PMID- 12003524
TI  - New strategy for the synthesis of iminoglycitols from amino acids.
AB  - A novel strategy for the enantioselective synthesis of polyhydroxypiperidines,
      which can be considered as iminoglycitols or 2,6-dideoxyazasugars, was developed.
      alpha-Benzolsulfonylamino esters served as a C(2)N building block while 2-bromo-3
      (bromomethyl)oxazoles and -thiazoles contributed a C3-unit to the final
      piperidine ring. At first a dihydropyridine ring was established via alkylation
      and bromine-lithium exchange. The keto group of the resulting 5,6
      dihydro[1,3]oxazolo- and 5,6-dihydro[1,3]thiazolo[4,5-c]pyridin-7(4H)-ones was
      reduced and, after alkylation reactions, the azole ring was cleaved, thus
      providing heteroatom substituents for the target piperdines. Protected 5-amino
      3,4-dihydroxy and 5-amino-3-hydroxy-4-thiohydroxypiperdines were obtained in the
      talose series while Mitsunobu reaction of the intermiediates provided access to
      the altrose series.

PMID- 12003525
TI  - Total synthesis of dysiherbaine.
AB  - A convergent total synthesis of the marine natural product dysiherbaine was
      accomplished. The key steps of the synthesis are an alkylation at the gamma
      carbon of a protected glutamate with a highly substituted pyran derived from
      mannose, which was followed by a ring-contraction cascade reaction, which
      simultaneously gave the tetrasubstituted carbon and the hexahydrofuro[3,2-b]pyran
      ring system of the natural product.

PMID- 12003526
TI  - Hydration with mercuric acetate and the reduction with 9-BBN-H of 2-(1-alkenyl)
      4,6-dimethyl-s-triazines.
AB  - Oxymercuration-demercuration of a double bond in conjugation with the 4,6
      dimethyl-s-triazin-2-yl substituent as in alkenes 1a,b gave anti-Markovnikov
      regioselectivity, which is explained by the electron-withdrawing nature of the
      triazinyl substituent. However, hydroboration of the conjugated alkenes with 9
      BBN-H gave the corresponding alkanes 5a-c under normal workup conditions with or
      without oxidation. With time and without workup the hydroboration of 1b gave
      spectral evidence for the formation of intermediates 9-13 resulting from the
      migration of the 9-BBN moiety from the alpha-carbon to a ring nitrogen with
      concurrent formation of an exocyclic double bond to an alpha-carbon of the ring.
      Hydrolysis of the intermediates gave 5a-c. A possible mechanism involving
      successive allylic rearrangements is presented.

PMID- 12003527
TI  - A study of aryl radical cyclization in enaminone esters.
AB  - Aryl radical cyclization in N-phenyl, N-benzyl, and N-phenethyl enaminone esters
      1a-f was studied. N-Benzyl and N-phenethyl enaminones afforded 5-exo and 6-exo
      cyclization products, respectively, but radical cyclization did not occur in N
      phenyl enaminones. The rate constants for the 5-exo and 6-exo cyclization
      processes in secondary enaminones were estimated as being on the order of 10(7)
      s(-1) at 353 K; since DNMR experiments showed the rate constant for rotation
      around the enaminone C3-N bond to be on the order of 10(4) s(-1) at this
      temperature, the initial enaminone configuration is maintained throughout the
      cyclization process. PM3 calculations suggested that the nonoccurrence of endo
      and 4-exo cyclizations is due to the corresponding transition structures
      involving significant distortion of the conjugated enaminone system.

PMID- 12003528
TI  - Crystal engineering of hydroxy group hydrogen bonding: design and synthesis of
      new diol lattice inclusion hosts.
AB  - The diols 7-11 have been synthesized, and their X-ray crystal structures
      determined, to learn how to influence and control lattice hydroxy group hydrogen
      bonding using crystal engineering ideas. To obtain new lattice inclusion hosts
      precise structural rules can be defined which enable the necessary supramolecular
      interactions to be duplicated. In this manner the helical tubuland 10 and
      ellipsoidal clathrate 11 hosts were obtained for the first time and their
      chloroform inclusion compounds characterized. New synthetic routes were utilized
      to obtain the bicyclo[3.3.2]decane and 9-thiatricyclo[4.3.1.1(3,8)]undecane
      frameworks present in these compounds. The solid-state conformations of
      bicyclo[3.3.2]decane derivatives 9 and 10 are compared with prior predictions and
      studies made on this uncommon ring system.

PMID- 12003529
TI  - Ethyl alpha-fluoro silyl enol ether: stereoselective synthesis and its aldol
      reaction with aldehydes and ketones.
AB  - Ethyl alpha-fluoro silyl enol ether is stereoselectively synthesized in high
      yield from inexpensive chlorofluoroacetate and Mg (or Zn) in DMF (or HMPA). Lewis
      acid promoted aldol reaction of this enol ether with aldehydes and ketones gives
      alpha-fluoro-beta-hydroxy esters in good to excellent yields.

PMID- 12003530
TI  - Syntheses of C12,N13 heterocyclic bridged fused indenopyrrolocarbazoles.
AB  - Tandem alkylation/cyclization of indenopyrrolocarbazole 4a, a C12 carbon analogue
      of indolocarbazole K252c, was carried out by general solid-phase and solution
      phase methods. Alkylation of fused pyrroloindenylcarbazole 4a derivatives with
      appropriate monoacetals of diketones afforded the corresponding C12-substituted
      acetal alcohols. Acid-catalyzed cyclization of these adducts yielded C12,N13
      bridged tetrahydrofuran, pyran, and dioxane compounds 10-13.

PMID- 12003531
TI  - Short and stereoselective total synthesis of furano lignans (+/-)-dihydrosesamin,
      (+/-)-lariciresinol dimethyl ether, (+/-)-acuminatin methyl ether, (+/-)
      sanshodiol methyl ether, (+/-)-lariciresinol, (+/-)-acuminatin, and (+/-)
      lariciresinol monomethyl ether and furofuran lignans (+/-)-sesamin, (+/-)
      eudesmin, (+/-)-piperitol methyl ether, (+/-)-pinoresinol, (+/-)-piperitol, and
      (+/-)-pinoresinol monomethyl ether by radical cyclization of epoxides using a
      transition-metal radical source.
AB  - Intramolecular radical cyclization of suitably substituted epoxy ethers 4a-g
      using bis(cyclopentadienyl)titanium(III) chloride as the radical source resulted
      in trisubstituted tetrahydrofurano lignans and 2,6-diaryl-3,7
      dioxabicyclo[3.3.0]octane lignans depending on the reaction conditions. The
      titanium(III) species was prepared in situ from commercially available titanocene
      dichloride and activated zinc dust in THF. Upon radical cyclization followed by
      acidic workup, epoxy olefinic ethers 4a-g afforded furano lignans dihydrosesamin
      1a, lariciresinol dimethyl ether 1b, acuminatin methyl ether 1e, and sanshodiol
      methyl ether 1g directly and lariciresinol 1h, acuminatin 1i, and lariciresinol
      monomethyl ether 1j after removal of the benzyl protecting group by controlled
      hydrogenolysis of the corresponding cyclized products. The furofuran lignans
      sesamin 2a, eudesmin 2b, and piperitol methyl ether 2e were also prepared
      directly by using the same precursors 4a-f on radical cyclization followed by
      treatment with iodine and pinoresinol 2h, piperitol 2i, and pinoresinol
      monomethyl ether 2j after controlled hydrogenolysis of the benzyl protecting
      group of the corresponding cyclized products. Two naturally occurring acyclic
      lignans, secoisolariciresinol 5h and secoisolariciresinol dimethyl ether 5b, have
      also been prepared by exhaustive hydrogenolysis of 2h and 2b, respectively.

PMID- 12003532
TI  - Kinetics of thermal gas-phase isomerizations and fragmentations of cis- and trans
      1-(E)-propenyl-2-methylcyclobutanes at 275 degrees C.
AB  - Kinetic studies of the thermal isomerization and fragmentation reactions
      exhibited by cis- and trans-1-(E)-propenyl-2-methylcyclobutanes at 275 degrees C
      in the gas phase have provided first-order rate constants for cis,trans
      interconversions of the cyclobutanes, 1,3-carbon migrations leading to 3,4- and
      3,6-dimethylcyclohexenes, isomerizations providing directly and indirectly four
      acyclic dienes, and fragmentations to ethylene, propene, and mixtures of
      pentadienes and hexadienes. Both cis and trans isomers of 1-(E)-propenyl-2
      methylcyclobutane form trans-3,4-dimethylcyclohexene faster than they are
      converted to cis-3,4-dimethylcyclohexene; the trans reactant gives rise to cis
      3,6-dimethylcyclohexene in preference to its trans isomer, while the cis starting
      material gives neither at measurable rates; both form the relatively minor
      product 1,6-(Z)-octadiene. The rate constants derived from 35 kinetic runs
      starting with four distinct 1-(E)-propenyl-2-methylcyclobutane samples are
      consistent to within narrow error limits. The stereomutations, isomerizations,
      and fragmentations of the 1-(E)-propenyl-2-methylcyclobutanes are interpreted in
      terms of competitive processes involving conformationally flexible short-lived 2
      (E)-octene-4,7-diyl and 3-methyl-5-(E)-heptene-1,4-diyl diradicals.

PMID- 12003533
TI  - Rearrangement pathways of 2-hydroxy-2-methylpropylidene: an experimental and
      computational study.
AB  - Photolysis of exo-2-(1a,9b-dihydro-1H-cyclopropa[l]phenanthren-1-yl)propan-2-ol
      in benzene-d(6) afforded phenanthrene and the beta-hydroxycarbene intermediate 2
      hydroxy-2-methylpropylidene. The carbene showed an overwhelming preference for
      1,2-methyl migration as evident from the formation of 2-butanone as the major
      product via the enol 2-hydroxy-2-butene. Also produced, albeit in smaller
      amounts, were 1-methylcyclopropanol and 2,2-dimethyloxirane from intramolecular
      insertion into the C-H and O-H bonds, respectively. These results stand in sharp
      contrast to the intramolecular reactions of simple alkylcarbenes which usually
      prefer insertion into C-H bonds over 1,2-alkyl migrations. Calculations at the
      B3LYP/6-311+G//B3LYP/6-31G level of theory give a lower activation barrier for
      1,2-methyl migration leading to the eventual formation of 2-butanone than for the
      other two pathways. The lower activation energy for methyl migration, relative to
      C-H and O-H insertions, strongly supports the observed experimental product
      distribution of the carbene. The parent carbene exists in three distinct
      conformations, each with stabilizing interactions between the adjacent bonds and
      the empty p orbital and the filled sp(2) orbital of the carbene center. The most
      stable conformer is perfectly poised for a 1,2-methyl migration as the C-CH(3)
      group is involved in a hyperconjugative interaction with the empty p orbital and
      the O-H bond is simultaneously interacting with the sp(2) lone pair of the
      carbene.

PMID- 12003534
TI  - A cis amide bond surrogate incorporating 1,2,4-triazole.
AB  - A novel cis amide bond surrogate incorporating 1,2,4-triazole was designed and
      synthesized by the reaction of a thionotripeptide, formic hydrazide, and
      mercury(II) acetate. This method of surrogate formation was also applicable to a
      cyclic thionopeptide.

PMID- 12003535
TI  - First synthesis of caerulomycin B. A new synthesis of caerulomycin C.
AB  - Caerulomycins produced by Streptomyces caeruleus are bipyridinic molecules
      endowed with antibiotic properties. The first synthesis of caerulomycin B (1) as
      well as a new synthesis of caerulomycin C (2) are reported. Starting from 3
      hydroxypyridine, the same methodology was used to prepare both compounds 1 and 2.
      Efficiently controlled reactions such as metalation to allow the synthesis of 2,6
      diiodo-3,4-dialkoxypyridines, which are key intermediates, and further halogen
      lithium exchange and cross-coupling to reach the targets molecules 1 and 2 have
      been developed.

PMID- 12003536
TI  - Dynamic NMR study of the rotation around "biphenyl-type" bonds in polycyclic
      sulfoxides.
AB  - In a recent paper, we reported on the base-catalyzed rearrangement of bis
      propargylic sulfoxides that eventually leads to polycyclic products featuring an
      unsaturated, cyclic substituent such as cyclohexenyl or phenyl. Due to steric
      constraints, the latter is positioned roughly perpendicularly to the tricyclic
      core, and in most cases, two rotamers can be observed in the ground state. In the
      present work, we report on the synthesis and the products of both symmetrical and
      asymmetrical starting materials. We also measure, by NMR techniques, the rotation
      rate of the side chain for several such polycyclic sulfoxides. The barriers for
      this process, which is similar to a biphenyl rotation, are very strongly
      dependent on the nature of the substrate, ranging between <7 and 21.0 kcal.mol(
      1) for sulfoxides with two five-membered rings and two seven-membered rings,
      respectively. These barriers can be successfully simulated by molecular-mechanics
      calculations, and the geometries of the transition states are discussed.

PMID- 12003537
TI  - Stereochemistry of the [4 + 2] cycloadditions of trans,trans- and cis,trans-2,4
      hexadiene to C(60).
AB  - The [4 + 2] cycloaddition of trans,trans-2,4-hexadiene with C(60) proceeds via a
      concerted mechanism with retention of stereochemistry in the cycloadduct 1a.
      However, when cis,trans-2,4-hexadiene reacts with C(60), isomerization of the
      cis,trans to the thermodynamically more stable trans,trans isomer occurs.
      Subsequently, the cis,trans diene isomerized to the trans,trans isomer and
      cycloadds to C(60), to form adduct 1a. When the reaction is carried out at higher
      temperatures, the formation of cycloadduct 1b is also obtained. This result is
      consistent with a concerted cycloaddition of cis,trans-2,4-hexadiene with C(60),
      which is more reactive at elevated temperatures and leads to the formation of the
      Diels-Alder adduct 1b.

PMID- 12003538
TI  - First synthesis and anticancer activity of phosmidosine and its related
      compounds.
AB  - This paper describes the first synthesis of phosmidosine and phosmidosine B,
      i.e., nucleotide antibiotics composed of 8-oxoadenosine and L-proline which are
      connected via a unique N-acyl phosphoramidate linkage. Phosmidosine has a yet
      undetermined chiral center at the phosphorus atom of the N-acyl phosphoramidate
      linkage. Phosmidosine B is a demethylated phosmidosine derivative with no
      chirality on the phosphorus. Phosmidosine B was successfully synthesized by the
      reaction of an N-acetyl-8-oxoadenosine 5'-O-phosphoramidite derivative with an N
      protected prolinamide in the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole. The
      successful synthesis of phosmidosine was achieved by use of a tert-butoxycarbonyl
      (Boc) group, which was found to be selectively introduced into the 7-NH function
      of 8-oxoadenosine and to serve as a pseudo-protecting group due to its steric
      effect in such manner that the unmasked 6-amino group was not phosphitylated.
      Final coupling reaction of the 8-oxoadenosine 5'-phosphoramidite derivative with
      N-tritylprolinamide followed by full deprotection gave a mixture of phosmidosine
      and its diastereoisomer. The (13)C NMR spectra of the diastereomers suggest that
      the slow-eluted diastereomer 1b is the naturally occurring phosmidosine. The
      growth inhibitory activity of phosmidosine 1b, its diastereomer 1a, and
      phosmidosine B in various tumor cell lines was evaluated by the MTT assay. As the
      result, phosmidosine B showed high anticancer activities and both the
      diastereomers 1a and 1b of phosmidosine isolated were found to have similar but
      approximately 10 times higher anticancer activities than phosmidosine B.
      Moreover, it turned out that these phosmidosine derivatives showed characteristic
      inhibitory activities against cancer cells independent of their p53 phenotypes.
      These results suggest that phosmidosine and its related compounds would be
      promising as a new type of anticancer agents having a wide range of inhibitory
      activities against tumor cells.

PMID- 12003539
TI  - Intramolecular radical cyclization-ring-closing metathesis approach to fused
      polycyclic ethers. Convergent synthesis and conformational analysis of the (E)FGH
      ring system of ciguatoxin.
AB  - A convergent synthetic route to the (E)FGH ring system 4 of ciguatoxins, the
      causative toxins for ciguatera fish poisoning, has been developed. The synthesis
      features convergent coupling to form dioxane acetal, regioselective acetal
      cleavage by diethylaluminum phenylthiolate or diisobutylaluminum phenylselenolate
      followed by intramolecular radical cyclization to construct the oxepane ring G,
      and a ring-closing metathesis reaction to form the hexahydrooxonine ring F. The
      hexahydrooxonine ring F of tetracyclic model system 4 existed as a 5:1
      equilibrium mixture of two conformers (UP and DOWN conformers), with the UP one
      predominating. This is the first illustration that reproduces the preference for
      the UP conformer over the DOWN one, which preference was observed for natural
      ciguatoxins.

PMID- 12003540
TI  - Sequential photostimulated reactions of trimethylstannyl anions with aromatic
      compounds followed by palladium-catalyzed cross-coupling processes.
AB  - The photostimulated reactions of several mono-, di-, and trichloroarenes and
      aryltrimethylammonium salts with Me(3)Sn(-) ions in liquid ammonia gave good
      yields of stannanes by the S(RN)1 mechanism. If the chloroarenes are not soluble
      in liquid ammonia, diglyme is another solvent to perform these reactions. The
      stannanes thus obtained can be arylated by further reaction with haloarenes
      through palladium-catalyzed reactions. If the palladium-catalyzed reaction is
      performed with a chloroiodoarene as substrate, the stannane reacts faster by the
      C-I bond via chemoselective cross-coupling reaction to give a chloroarene as
      product, which can be further arylated by a consecutive S(RN)1-Stille reaction or
      react with other substrates by another palladium-catalyzed reaction. These
      sequential reactions can also be performed with substrates with two leaving
      groups to give products in high yields.

PMID- 12003541
TI  - A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition for the
      synthesis of substituted chromanes.
AB  - A stereoselective intramolecular 1,3-dipolar nitrone cycloaddition useful in the
      synthesis of chromanes is described. The reaction relies on the use of a chiral
      auxiliary on the nitrone partner. Key to the success of the reaction is the
      choice of auxiliary and the choice of Lewis acid catalyst. Utilizing an auxiliary
      with a pendant coordinating group, and Zn(OTf)(2) as the Lewis acid,
      diastereoselectivities up to 22:1 could be achieved.

PMID- 12003542
TI  - Racemization of (S)-profen thioesters by strong neutral bases in nonpolar organic
      solvents: implication for ion-pair kinetic basicity.
AB  - The racemization of (S)-profen 2,2,2-trifluoroethyl thioesters in isooctane with
      trioctylamine as base was carried out, in which the Hammett equation log(k(int))
      = 3.584sigma - 3.745 was successfully applied to describe the electron
      withdrawing effect of the substituents to the alpha-phenyl moiety of the
      thioesters. A combination of neutral strong organic bases with different nonpolar
      solvents was employed to determine the second-order interconversion constants for
      the racemization of (S)-naproxen 2,2,2-trifluoroethyl thioester, in which solvent
      hydrophobicity was found to have less effect on the racemization. Implication for
      ion-pair kinetic basicity scale for the neutral strong bases in isooctane was
      further discussed.

PMID- 12003543
TI  - Facile syntheses of all possible diastereomers of conduritol and various
      derivatives of inositol stereoisomers in high enantiopurity from myo-inositol.
AB  - Phosphoinositide-based signaling processes are crucially important in
      intracellular signal transduction events. Inositol phosphate analogues have been
      useful in probing the structure-activity relationships between inositol
      phosphates and biomacromolecules, and in studying biological functions of newly
      found inositol phosphates. Thus, a systematic and ready access to inositol
      stereoisomers is highly desirable. And practical and convenient syntheses of
      conduritols and related compounds are also important because of their biological
      activities and their synthetic utilities in the preparation of other bioactive
      molecules. We herein report the first syntheses of all possible diastereomers of
      conduritol and various derivatives of eight inositol stereoisomers in high
      enantiopurity from myo-inositol, which involve efficient enzymatic resolution of
      the intermediates conduritol B and C derivatives, followed by oxidation-reduction
      or the Mitsunobu reaction, and cis-dihydroxylation in stereo- and regioselective
      manners.

PMID- 12003544
TI  - (1Z,3Z)-1,4-Di(pyridin-2-yl)buta-1,3-diene-2,3-diol: the planar highly conjugated
      symmetrical enediol with multiple intramolecular hydrogen bonds.
AB  - 1H, (13)C, and (15)N NMR spectral data show that in chloroform solution (1Z,3Z)
      1,4-di(pyridin-2-yl)buta-1,3-diene-2,3-diol, OO, is in ca. 9:1 equilibrium with
      (3Z)-3-hydroxy-1,4-di(pyridin-2-yl)but-3-en-2-one, OK, while no 1,4-di(pyridin-2
      yl)-2,3-butanedione, KK, was detected. The species present in the tautomeric
      mixture were identified by comparing their experimental chemical shifts with
      those known for similar compounds as well as with the theoretically calculated
      (GIAO-HF/DFT) values. Ab initio calculations show that OK and especially the
      highly conjugated OO forms are preferred in the tautomeric mixtures both in vacuo
      and in chloroform solution. Comparison of experimental (Arrhenius) and calculated
      (ab initio) energies of OK shows that the MP2/6-31G//RHF/6-31G method gives the
      most precise results. There are one and two strong O-H.N hydrogen bonds present
      in the molecules of the former and latter compound, respectively. Other
      tautomeric forms, e.g., dienaminedione [(1Z,4Z)-1,4-di[pyridin-2(1H)
      ylidene]butane-2,3-dione], and their rotamers were found to have higher energies.
      The single-crystal X-ray diffraction studies show that dienediol OO is the only
      tautomeric form present in the crystal at 173 K. Its almost perfectly planar
      molecule is stabilized by two strong intramolecular O-H.N hydrogen bonds.

PMID- 12003545
TI  - Synthesis of a potent antagonist of E-selectin.
AB  - A synthesis of an antagonist of E-selectin previously reported by a group at
      Novartis Pharma in Basel is described. An important feature involves the
      formation of an ether linkage based on a Rh(II)-catalyzed reaction.
      Stereocontrolled glycosylations rely on the anomeric activation of 2-pyridylthio
      carbonate as leaving group for the attachment of beta-D-galactopyranosyl and
      alpha-L-fucopyranosyl units on a common 1,5-anhydro D-glucitol scaffold.

PMID- 12003546
TI  - Asymmetric synthesis of metallocenes through enantioselective addition of
      organolithium reagents to 6-(dimethylamino)fulvene.
AB  - Enantioselective addition of aryllithiums 2a-d (Ar = Ph (a), 2-MeC(6)H(4) (b), 2
      MeOC(6)H(4) (c), 1-naphthyl (d)) to 6-(dimethylamino)fulvene (1) in the presence
      of (-)-sparteine in toluene at -78 degrees C generated chiral
      cyclopentadienyllithiums (4) substituted with an N,N-dimethylamino(aryl)methyl
      group, where the enantioselectivities are 51, 91, 90, and 83% for 4a, 4b, 4c, and
      4d, respectively. Treatment of the chiral cyclopentadienides 4 with FeCl(2) or
      Fe(acac)(2) gave ferrocenes, which contain an N,N-dimethylamino(aryl)methyl side
      chain on both of the cyclopentadienyl rings. The enantiomeric purity of the
      chiral ferrocenes 7 thus obtained is 99% ee or higher for those containing a 2
      MeC(6)H(4) (7b) or a 2-MeOC(6)H(4) (7c) group.

PMID- 12003547
TI  - Radical contraction of 1,3,2-dioxaphosphepanes to 1,3,2-dioxaphosphorinanes: a
      kinetic and (17)O NMR spectroscopic study.
AB  - Two diastereomeric 5-bromo-4-phenyl-2-phenoxy-2-oxo-1,3,2-dioxophosphepanes have
      been synthesized and used to study the contraction of 4-phenyl-2-phenoxy-2-oxo
      1,3,2-dioxophosphorinan-5-yl radicals. Kinetics were determined by competition
      methods and demonstrate Arrhenius parameters typical of rearrangements of this
      kind. Isotopic labeling reveals that all rearrangements are formally of the 1,2
      type with retention of configuration at phosphorus. Analysis of the
      stereochemistry of the rearrangements, however, reveals the two diastereomers to
      take different paths with respect to the geometry of the presumed alkene radical
      cation intermediate.

PMID- 12003548
TI  - "Fleximers". Design and synthesis of a new class of novel shape-modified
      nucleosides(1).
AB  - A new class of shape-modified nucleosides is introduced. These novel "fleximers"
      feature the purine ring systems of adenosine, inosine, and guanosine split into
      their individual imidazole and pyrimidine components (as in 1-3). This structural
      modification serves to introduce flexibility into the nucleoside while still
      retaining the elements essential for recognition. As a consequence, these novel
      fleximers should find use as bioprobes for investigating enzyme-coenzyme binding
      sites as well as nucleic acid and protein interactions. Their design and
      synthesis are described.

PMID- 12003549
TI  - Some aspects of palladium-catalyzed cycloalkenylation: developments of
      environmentally benign catalytic conditions and demonstration of tandem
      cycloalkenylation.
AB  - The influences of catalysts, substituent groups, and solvents on the palladium
      catalyzed cycloalkenylation of cross-conjugated silyl enol ethers of 2-tert
      butyldimethylsiloxy-5-(2-propenyl)-1,3-cyclohexadiene derivatives have been
      investigated. The catalytic reaction proceeded smoothly, even in aqueous media.
      The product ratios were influenced by the structure of substrates as well as
      solvents. In addition, it was found that the reaction is applicable to a tandem
      cyclization for the construction of cedrane skeleton.

PMID- 12003550
TI  - Design and synthesis of a novel class of constrained tricyclic pyrrolizidinone
      carboxylic acids as carbapenem mimics.
AB  - A series of tricyclic pyrrolizidinone carboxylic acids harboring an angular
      methano group were synthesized as mimics of carbapenems and carbapenams. A key
      reaction involved a novel intramolecular cyclopropanation mediated by a
      trimethylstannylmethyl group and an adjacent iminium ion. Enolate chemistry on a
      tricyclic lactam ring unit allowed the introduction of various substituents.
      Further elaboration afforded tricyclic pyrrolidinone carboxylic acids, which were
      found to be inactive as inhibitors against a panel of bacterial strains. However,
      the antibacterial activity of ceftazidine was enhanced in the presence of the
      tricyclic analogues.

PMID- 12003551
TI  - Cobalt-phosphite-catalyzed asymmetric Pauson-Khand reaction.
AB  - A complex formed from dicobalt octacarbonyl and a chiral aryl bisphosphite served
      as a catalyst for the intramolecular asymmetric Pauson-Khand reaction. Bicyclic
      cyclopentenones were obtained in up to 75% enantiomeric excess. For a terminal
      1,6-enyne, the incremental enantiomeric excess was found to increase from 4 to
      26% over the course of the reaction. The scope of this process was examined for a
      variety of 1,6- and 1,7-enynes, and a moderate degree of enantioselectivity was
      maintained only in the case of aryl-substituted 1,6-enynes.

PMID- 12003553
TI  - Facile preparation of benzo[4,5]thieno[2,3-b]pyridines and naphtho[b
      4,5]thieno[2,3-b]pyridines via the reaction of Barton esters and benzynes.
AB  - Titled compounds were prepared in a one-pot synthesis by generating symmetrically
      substituted benzyne intermediates by the diazotization of anthranilic acids in
      the presence of Barton esters. Unsymmetrically substituted aryne either gave
      mixtures of regioisomers or failed. However, nitro and methyl derivatives of
      titled compounds could be obtained as single products using appropriately
      substituted Barton esters.

PMID- 12003552
TI  - Mimicry of annonaceous acetogenins: enantioselective synthesis of a (4R)-hydroxy
      analogue having potent antitumor activity.
AB  - The (4R)-hydroxylated analogues of annonaceous acetogenin mimicking compound 2
      were designed and synthesized structurally on the basis of the naturally
      occurring annonaceous acetogenin bullatacin, which was discovered as a typical
      member of the novel family of polyketides with potent cytotoxicity, antitumoral,
      and other biological activities. The preliminary screenings show that the IC(50)
      values of 2 were 1.6 x 10(-3) and 8 x 10(-2) microg/mL against HT-29 and HCT-8,
      respectively. A remarkable enhancement effect was observed by the activity
      comparison of 1c and its (4R)-hydroxylated analogue 2.

PMID- 12003554
TI  - Synthesis of azapolycyclic systems via the intramolecular [4 + 2] cycloaddition
      chemistry of 2-(alkylthio)-5-amidofurans.
AB  - A series of 2-(methylthio)-5-amidofurans containing tethered unsaturation were
      prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate
      (DMTSF) with beta-alkoxy-gamma-dithiane amides 13-16 and 27-32 in 40-70% yield.
      Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction
      (IMDAF). With the exception of 45 and 46, the oxa-bridged cycloadducts could not
      be isolated but immediately underwent a 1,2-methylthio shift to form bicyclic
      lactams in 60-100% yield. It was determined that incorporation of the amido
      carbonyl in the tether allowed the IMDAF reaction to proceed at a lower
      temperature. A dramatic example of this is seen in the IMDAF reaction of furan
      35, in which the presence of an amido carbonyl as part of the dienophile tether,
      as opposed to the annealed ring (66) or the lack of a carbonyl (67), was
      necessary for the cycloaddition to occur. Furan 37, annealed to an azepine ring,
      underwent the IMDAF reaction at or below room temperature. To identify structural
      features that promote the IMDAF reaction, a computational study was undertaken.
      Ground-state and transition-state energies were calculated for furans 17, 33, 37,
      and 64 using the Becke 3LYP/6-31G model. The theoretical results were in good
      agreement with those observed. The results indicate that the incorporation of an
      amide carbonyl as part of the tether system works to place the dienophile in
      closer proximity to the furan ring, thereby lowering the activation energy needed
      to reach the transition state.

PMID- 12003555
TI  - Iodine(III)-mediated generation of nitrogen-tethered orthoquinol acetates for the
      construction of oxygenated indole, quinoline, and phenanthridine alkaloid motifs.
AB  - Functionalized indole and quinoline derivatives are conveniently prepared from
      nitrogen-tethered 2-methoxyphenols via phenyliodine(III) diacetate mediated
      oxidative acetoxylation, followed by a fluoride- or base-induced intramolecular
      nucleophilic addition reaction. This regioselective Michael-type addition step is
      further discussed in view of the rearrangement of orthoquinol acetate
      intermediates into paraquinol acetates that is sometimes observed in situ.
      Application of this methodology to the synthesis of a functionalized
      phenanthridine, and its potential for the construction of polyoxygenated lycorine
      type alkaloid skeleta are here described.

PMID- 12003556
TI  - Synthesis of substituted isoquinolines by electrophilic cyclization of
      iminoalkynes.
AB  - The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous
      pyridinecarbaldehydes have been cyclized under very mild reaction conditions in
      the presence of I(2), ICl, PhSeCl, PhSCl, and p-O(2)NC(6)H(4)SCl to give the
      corresponding halogen-, selenium-, and sulfur-containing disubstituted
      isoquinolines and naphthyridines, respectively. This methodology accommodates a
      variety of iminoalkynes and affords the anticipated heterocycles in moderate to
      excellent yields. Monosubstituted isoquinolines and naphthyridines have been
      synthesized by the metal-catalyzed ring closure of these same iminoalkynes. The
      silver-catalyzed ring closure is highly effective in cyclizing aryl-, alkenyl-,
      and alkyl-substituted iminoalkynes at 50 degrees C.

PMID- 12003557
TI  - Addition of heteroaromatics to alkylidenecyclopropanes catalyzed by palladium.
AB  - The reaction of heteroaromatics, such as furans, thiophenes, thiazoles, and
      pyrroles, with alkylidenecyclopropanes proceeded smoothly in the presence of
      palladium catalysts, producing the corresponding alpha-allylated products in good
      to high yields. For example, the reaction of 3-butylpentylidenecyclopropane (1a)
      with 2-methylfuran (2a), ethyl 2-thiophenecarboxylate (4a), 2-isobutylthiazole
      (6a), and 1-methylpyrrole (11b) gave the alpha-allylated products in 70%, 66%,
      77%, and 30% yield, respectively. The reaction proceeded predominantly through
      distal bond cleavage. The order of reactivity of heteroaromatics toward 1a is as
      follows: furan > thiophene approximately thiazole (5-position) > thiazole (2
      position) approximately pyrrole. This methodology provides a means for
      introducing an allylic group to various kinds of heteroaromatics under mild
      conditions.

PMID- 12003558
TI  - Enantioselective aziridination using copper complexes of biaryl Schiff bases.
AB  - Racemic 2,2'-diamino-6,6'-dimethylbiphenyl is resolved using simulated moving bed
      chromatography, and the absolute configuration of the enantiomers is confirmed
      via the X-ray crystal structure of a derivative. The diamine is condensed with a
      range of aldehydes to give bidentate aldimine proligands L. Molecular structures
      of the complexes formed between L and Cu(I) fall into two classes; bimetallic
      double helices ([Cu(2)L(2)](2+)) and monometallic ([CuL](+)). The latter are
      strikingly more efficient in the aziridination of alkenes than are the former in
      terms of rate, turnover, and enantioselection. In particular, the imine ligand
      formed from the diamine and 2,6-dichlorobenzaldehyde gives, in combination with
      Cu(I) or Cu(II), up to 99% ee in the aziridination of 6-acyl-2,2-dimethylchromene
      and 88-98% ee for a range of cinnamate esters. Styrenic and other alkenes are
      converted with lower selectivities (5-54%). The catalytic system shows a linear
      response in product ee to catalyst ee, and the product ee does not vary
      significantly during the reaction. UV spectrophotometric investigations indicate
      that conversion of Cu(I) to Cu(II) is not essential for catalysis but that Cu(II)
      is probably also a competent system.

PMID- 12003560
TI  - Use of gas-phase (1)H NMR to determine the kinetics of unimolecular rearrangement
      of 2,2-dichloro-1-methylenecyclopropane and the bimolecular dimerization of
      (dichloromethylene)cyclopropane.
AB  - Gas-phase (1)H NMR analysis has been applied to investigate the kinetics of the
      unimolecular rearrangement of 2,2-dichloro-1-methylenecyclopropane (1) to
      (dichloromethylene)cyclopropane (2) [k(1) = 7.9 x 10(12) exp(-34.4 +/- 0.6 kcal
      mol(-1)/RT)], as well as for the subsequent second-order dimerization of 2 [k(2)
      = 2.4 x 10(6) exp(-18.5 +/- 1.1 kcal mol(-1)/RT)] to form 7,7,8,8
      tetrachlorodispiro[2.0.2.2]octane (3)

PMID- 12003559
TI  - Sequenced reactions with samarium(II) iodide. Sequential intramolecular
      Reformatsky/nucleophilic acyl substitution reactions for the synthesis of medium
      sized carbocycles.
AB  - Samarium(II) iodide was used to access eight- and nine-membered carbocycles via a
      domino reaction comprised of a Reformatsky reaction followed by a nucleophilic
      acyl substitution reaction. This method represents a general and efficient
      approach to a variety of highly functionalized, stereodefined carbocycles.

PMID- 12003561
TI  - New building blocks for fluorinated bioimidazole derivatives II: preparation of
      beta-fluorourocanic acids.
AB  - Replacement of vinyl hydrogen with fluorine is based on addition of an FBr
      equivalent to a double bond followed by HBr elimination. This sequence has been
      adapted to prepare 3-fluoro-3-imidazolyl-propenoic acids (beta-fluorourocanic
      acids), and the related fluorinated imidazolyl propenals and prop-2-en-1-ols,
      from urocanic acid. Tritylation of the imidazole nitrogen was necessary for
      successful addition of "FBr" to the double bond, and prior reduction of the
      carboxyl group to the alcohol was required to provide the desired
      chemoselectivity in the elimination of HX. Reoxidation and deprotection produced
      the fluorinated urocanic acids.

PMID- 12003562
TI  - Photolabile precursors of cyclic nucleotides with high aqueous solubility and
      stability.
AB  - Photolabile phosphotriester derivatives of cyclic AMP and cyclic GMP are
      described, where the additional group on the phosphate is a 2-nitrobenzyl that
      bears an electron-withdrawing and dianionic substituent. This confers high
      aqueous solubility and excellent resistance to hydrolysis of the phosphotriester
      (t(1/2) for hydrolysis at pH 7, 22 degrees C, is >3 months for the axial isomers
      3a and 4a and >1 month for the equatorial isomers 3b and 4b). The photolysis
      quantum yields are in the range 0.15-0.24, and the product release rate upon
      flash photolysis is 1.7 s(-1) at pH 7.0, 20 degrees C.

PMID- 12003563
TI  - Chiral fluoro ketones for catalytic asymmetric epoxidation of alkenes with oxone.
AB  - Two structurally dissimilar, chiral fluoro ketones have been prepared and their
      potential as enantioselective catalysts for asymmetric epoxidation with Oxone has
      been evaluated. The tropinone-based ketone (-)-5 was easily prepared and showed
      excellent reactivity but only modest enantioselectivity. The biphenyl-based
      ketone (-)-6 was prepared in a somewhat lengthy synthesis (along with its
      monofluoro and geminal fluoro analogues). This ketone exhibited only modest
      reactivity; 30 mol % of (-)-6 was needed to bring about complete conversion in a
      reasonable time. The enantioselectivity of this catalyst was generally much
      higher, but again very substrate dependent.

PMID- 12003564
TI  - Photocycloaddition of four-carbon-tethered pyridones. Intramolecular hydrogen
      bonding and facilitated amide hydrolysis by a proximal secondary alcohol.
AB  - Four-carbon-tethered pyridones undergo photocycloaddition to give exclusively
      trans-[4 + 4] products. The presence of a tether alcohol engenders a solvent
      dependent diastereoselectivity for the cycloaddition by intramolecular hydrogen
      bonding to the adjacent pyridone. Following cycloaddition, the alcohol can
      deliver a carbonyl group to the proximal, hindered amide nitrogen, leading to a
      very facile amide hydrolysis.

PMID- 12003565
TI  - Concise synthesis of cyclic ethers via the palladium-catalyzed coupling of ketene
      acetal triflates and organozinc reagents. Application to the iterative synthesis
      of polycyclic ethers.
AB  - The reaction of the ketene acetal triflates 9a-e and a zinc homoenolate 10 in the
      presence of a catalytic amount of Pd(PPh(3))(4) gave the enol ethers 11a-e in
      good yields. The products were converted to the corresponding cyclic ethers 14a
      and 14b by hydroboration and lactonization. The present methodology allowed us to
      synthesize the DE and GH ring segment of gambierol in a concise manner. Iterative
      syntheses of the polycyclic ethers 26 and 32 are also described.

PMID- 12003566
TI  - A novel water-soluble Hantzsch 1,4-dihydropyridine compound that functions in
      biological processes through NADH regeneration.
AB  - A novel Hantzsch 1,4-dihydropyridine derivative could function in an organic
      solvent-free solution, and thus it could function in biological systems. These
      functions can be accomplished through regeneration of the reduced form of
      nicotinamine adenine dinucleotide (NADH), an essential compound for living
      organisms. The results obtained here demonstrate the usefulness of a water
      soluble Hantzsch 1,4-dihydropyridine derivative and its wide applicability as a
      chemical energy source, which drives various biological processes efficiently.

PMID- 12003567
TI  - An efficient synthesis of the new benzo[c]pyrido[2,3,4-kl]acridine skeleton.
AB  - A series of molecules of therapeutic interest, possessing the new skeleton of 1H
      benzo[c]pyrido[2,3,4-kl]acridine with acyl or aminoacyl and methoxy or
      aminoalkoxy substituents on the aromatic homocycles were synthesized by means of
      a Friedlander-type reaction. The requisite 5-aminodihydroquinoline-4-ones 1,
      whose preparation is described, were reacted with the appropriate alpha
      tetralones 2 using an acidic catalyst (PPTS) under azeotropic conditions.
      Optimized reaction time and yield depend on temperature, which must not be below
      90 degrees C.

PMID- 12003568
TI  - Synthesis of enantiopure 3-azabicyclo[3.3.0]octen-7-one derivatives via
      intramolecular Pauson-Khand cycloaddition reaction using tri-O-acetyl-D-glucal as
      starting material.
AB  - Some N-substituted-3-azabicyclo[3.3.0]octen-7-one derivatives have been
      synthesized in an enantiomerically pure form starting from tri-O-acetyl-D-glucal
      via intramolecular Pauson-Khand (IPK) cycloaddition.

PMID- 12003569
TI  - Halogen-halogen interactions in halomethanes.
AB  - We report the study of the electronic structure of CHFI(2), CHBrI(2), CHBr(2)I,
      CHClI(2), and CHCl(2)I using VUV photoelectron spectroscopy (UPS). The lone pair
      orbital interactions are discussed on the basis of experimental results and
      comparisons with other halomethanes.

PMID- 12003570
TI  - A general asymmetric synthesis of syn- and anti-beta-substituted cysteine and
      serine derivatives.
AB  - A stereodivergent synthetic route has been developed to make the optically pure
      anti- and syn-beta-substituted cysteine and serine derivatives. In this approach,
      the key intermediates, > 94% enantiomerically pure cyclic sulfates 3 and
      aziridines 7, were prepared from alpha,beta-unsaturated esters 1, employing the
      Sharpless asymmetric dihydroxylation. The high regio- and stereoselective ring
      opening reactions of cyclic sulfates and aziridines provided enantiomerically
      pure beta-substituted cysteine and serine derivatives.

PMID- 12003571
TI  - Thallium trinitrate mediated oxidation of 3-alkenols: ring contraction vs
      cyclization.
AB  - The reaction of a series of six-membered ring 3-alkenols with thallium trinitrate
      (TTN) in three different experimental conditions was studied. Either cyclization
      products or ring contraction products were obtained, depending on the structure
      of the substrate as well as the nature of the solvent. The reaction of a seven
      membered ring 3-alkenol with TTN led to the ring contraction product exclusively.

PMID- 12003572
TI  - Enantioselective desymmetrization of meso bicyclic hydrazines: a novel approach
      to the asymmetric synthesis of polysubstituted amino cyclopentanic cores.
AB  - Catalytic asymmetric hydroboration can be successfully applied to meso bicyclic
      hydrazines. The resulting alcohols are of great synthetic interest and can lead
      in a straightforward manner to cyclopentanic diamino alcohols with good
      enantiomeric purity.

PMID- 12003573
TI  - A novel approach to the synthesis of amino-sugars. Routes to selectively
      protected 3-amino-3-deoxy-aldopentoses based on pyridinium salt photochemistry.
AB  - A new approach for the synthesis of selectively blocked 3-amino-3
      deoxyaldopentoses is presented. The strategy is based on employment of a
      pyridinium salt photocyclization-aziridine ring-opening sequence to prepare
      stereochemically defined, enantiomerically enriched aminocyclopentendiol
      derivatives. Ring-opening reactions transform these substances into terminally
      differentiated aminopolyols, which serve as precursors to the target amino
      aldopentoses. The utility of this strategy is demonstrated by its application to
      the syntheses of protected derivatives of D- and L-3-amino-3-deoxyxylose, L-3
      amino-3-deoxyarabinose, and a late-stage intermediate in a potential route to N
      acetylneuraminic acid.

PMID- 12003574
TI  - Synthesis of 1,1'-binaphthyl-based enantiopure C(60) dimers.
AB  - The first enantiomerically pure and soluble C(60) dimers have been synthesized
      from suitably functionalized 1,1'-binaphthyl derivatives by 1,3-dipolar
      cycloaddition of the respective in situ generated diazo compounds to C(60). These
      systems exhibit optical and electrochemical activity.

PMID- 12003575
TI  - Substitution effect, absorption, and fluorescence behaviors of 11,12-benzo
      1,7,10,13-tetraoxa-4-aza- cyclopentadec-11-ene (benzoaza-15-crown-5) derivatives
      upon cation complexation in solvent extraction.
AB  - Substitution effect, absorption, and fluorescence behaviors of some benzoaza-15
      crown-5 derivatives upon cation complexation in solvent extraction were studied.
      The introduction of a substituent on the nitrogen atom in benzoaza-15-crown-5
      enhanced extractabilities in the solvent extraction of aqueous alkali metal
      picrates. The nondonating substituents raised the cation selectivity for Na(+)
      over K(+), but the donating substituents reduced the cation selectivity. The
      absorption and fluorescence spectral behavior was different with the alkali metal
      cations.

PMID- 12003576
TI  - Synthesis of a new C(32)H(12) bowl-shaped aromatic hydrocarbon:
      acenaphtho[3,2,1,8-ijklm]diindeno[4,3,2,1-cdef:1',2',3',4'-pqra]triphenylene.
AB  - The flash vacuum pyrolysis (FVP) of 1,2-bis(2-bromophenyl)-4,9-dibromocorannulene
      leads to a new C(32)H(12) buckybowl.

PMID- 12003578
TI  - Impact of adenotonsillectomy on quality of life in children with obstructive
      sleep disorders.
AB  - OBJECTIVES: To determine the impact of adenotonsillectomy on quality of life
      (QOL) in children with obstructive sleep disorders (OSDs) before and after
      surgery. DESIGN: Prospective, observational, before-and-after trial. SETTING:
      Seven tertiary pediatric otolaryngology practices. PATIENTS: Convenience sample
      of 101 children (mean age, 6.2 years) with adenotonsillar hypertrophy and OSD
      scheduled for adenotonsillectomy. INTERVENTION: Adenotonsillectomy was performed
      in children for OSDs. Quality of life was assessed using the Obstructive Sleep
      Disorders-6 survey, a validated instrument for detecting QOL change in children
      with OSDs. Surveys were completed at the initial office visit (visit 1), the day
      of surgery (visit 2), and at the postoperative office visit (visit 3). Physical
      characteristics were assessed using tonsillar and orocraniofacial scales (visit
      1). Satisfaction with health care decisions was assessed using the Satisfaction
      With Decision and Satisfaction With Office Visit scales (visit 1). MAIN OUTCOME
      MEASURES: Short-term changes in QOL before (visits 1 and 2) and after (visits 2
      and 3) surgery. RESULTS: Changes in QOL before surgery were trivial or small, and
      smaller than changes after surgery (mean change score, 0.18 vs 2.3; P<.001).
      Large, moderate, and small improvements in QOL were seen in 74.5%, 6.1%, and 7.1%
      of children, respectively. Sleep disturbance, caregiver concern, and physical
      suffering were the most improved domains, although significant changes also
      occurred for speech and swallowing problems, emotional disturbance, and activity
      limitations. Five percent of children had poorer QOL after surgery, but no
      predictive factors were identified. CONCLUSION: Adenotonsillectomy produces large
      improvements in at least short-term QOL in most children with OSDs.

PMID- 12003579
TI  - Multivariate analyses to assess treatment effectiveness in advanced head and neck
      cancer.
AB  - OBJECTIVE: To assess relative benefit of combined radiotherapy and surgery over
      single-modality treatment for advanced-stage squamous cell carcinoma of the
      aerodigestive tract by means of several multivariable analyses to control for
      patient variables. DESIGN: Medical chart review. SETTING: University medical
      center. PATIENTS AND METHODS: The study included 532 patients receiving initial
      therapy between January 1, 1980, and December 31, 1989. Three multivariate
      techniques (multiple logistic regression, propensity score stratification, and
      conjunctive consolidation) were used to compare outcomes for treatment groups.
      MAIN OUTCOME MEASURE: Five-year survival. RESULTS: Survival for radiation,
      surgery, and combined treatment groups were 24%, 40%, and 46%, respectively. With
      the use of multiple logistic regression to control patient variables, the
      radiation group had a significantly lower survival than the combined therapy
      group (risk ratio, 2.24; 95% confidence interval, 1.32-3.80), while there was no
      statistical difference for the surgery group compared with the combined therapy
      group (risk ratio, 1.26; 95% confidence interval, 0.78-2.03). When analyzed by
      propensity score, 5-year survival was higher in each quintile for the combined
      therapy group than for the group who received radiation alone (P =.002). There
      was no significant difference in survival between the surgery and combined
      treatment groups (P =.25). Conjunctive consolidation was used to create a
      clinical staging system to compare outcomes across treatment groups. In each
      clinical severity stage, radiation alone had a lower survival than combined
      therapy (P =.001), while no statistical difference was noted between surgery and
      combined therapy (P =.50). CONCLUSIONS: All 3 statistical techniques showed a
      significantly lower survival for patients treated with radiation alone vs
      combined therapy. No significant difference was noted between surgery and
      combined therapy. Propensity score analysis and conjunctive consolidation are
      useful techniques to control prognostic variables in cancer database studies and
      should be used in future outcome studies that address more current treatment
      dilemmas in head and neck oncology.

PMID- 12003580
TI  - Predictors of perioperative complications in head and neck patients.
AB  - BACKGROUND: Patients with significant medical problems requiring major
      otolaryngology procedures are at high risk for both medical and surgical
      complications. OBJECTIVE: To identify risk factors associated with perioperative
      complications in medically compromised patients undergoing major otolaryngology
      procedures. METHODS: Ninety-three consecutive patients with significant comorbid
      medical illnesses (eg, diabetes, hypertension) undergoing major head and neck
      surgical procedures were referred to a medical consultation center for
      preoperative assessment and medical management. Patient and surgical
      characteristics as well as perioperative complications were identified and
      recorded. Univariate and multivariate analyses were performed to determine which
      characteristics were associated with complications. RESULTS: Thirty-two patients
      (34%) had postoperative complications. Twenty-six patients (28%) had serious
      medical complications, and 18 (19%) had surgical complications. No deaths
      occurred in the study population. On univariate analysis, the factors associated
      with all complications included history of hepatitis, flap reconstruction,
      oncologic surgery, preoperative radiation therapy, preoperative gastrostomy
      placement, intraoperative transfusion, anesthesia time (> or =8 hours), and those
      with greater intraoperative fluid replacement and estimated blood losses. Only
      anesthesia time (> or =8 hours) remained independently significant on
      multivariate analysis. A history of hepatitis and prolonged anesthesia time were
      the only independent predictors of medical complications. The only independent
      predictor of surgical complications was the volume of intraoperative fluid
      administered. CONCLUSIONS: Prolonged anesthesia times of 8 hours or more, a
      history of hepatitis, and large-volume intraoperative fluid resuscitations
      predicted adverse outcomes. Special care must be taken in counseling these
      patients preoperatively and in caring for them during their operative and
      postoperative course.

PMID- 12003581
TI  - Markers for nodal metastasis in head and neck squamous cell cancer.
AB  - OBJECTIVE: To identify markers that are relevant as predictors of lymph node
      metastasis in head and neck squamous cell cancer. DESIGN: Expression of p53, Rb,
      cyclin D1, E-cadherin, and epithelial cell adhesion molecule was examined using
      immunohistochemical analysis and traditional histological parameters, and the
      correlation of these markers with the histologically verified presence of
      regional metastases was determined. SUBJECTS: The study sample comprised 121
      patients with head and neck squamous cell cancer from whom paraffin-embedded
      material of primary tumors was used. RESULTS: Lymph node metastasis was
      correlated with the loss of expression of Rb (P =.04) and marginally correlated
      with the loss of expression of E-cadherin (P =.06). If the results are broken
      down to subsites, loss of E-cadherin expression in oral cancer (P =.04) and
      absence of eosinophilic infiltration in laryngeal cancer (P =.003) correlated
      with nodal metastasis. None of the other markers correlated. A combination of
      relevant parameters did not result in a much stronger correlation. CONCLUSIONS:
      The expression of the investigated genetic markers and histopathological features
      of primary tumors can supply limited information on the metastatic behavior of
      tumors. Although the use of markers for regional metastasis would be a welcome
      additional tool, these results do not warrant the use of these parameters for
      clinical decision making concerning the treatment of the neck in patients with
      head and neck squamous cell cancer.

PMID- 12003582
TI  - Parotidectomy in the treatment of aggressive cutaneous malignancies.
AB  - BACKGROUND: Aggressive nonmelanoma skin cancer (ANMSC) of the head and neck may
      require parotidectomy because of neurotropic spread, direct invasion of the
      parotid gland, or parotid metastasis. OBJECTIVE: To review our experience with
      parotidectomy in the treatment of these tumors to examine the indications for
      this procedure and to analyze treatment outcomes. We emphasize the importance of
      early identification of an ANMSC and a systematic approach to treatment. DESIGN:
      Review of 23 patients with an ANMSC who required parotidectomy with or without
      facial (VII) nerve sacrifice between January 5, 1996, and December 27, 1999.
      Median follow-up for all patients was 24 months. SETTING: Academic tertiary care
      referral center. PATIENTS: This study focused on 23 (median age, 71 years) of 54
      patients treated for an ANMSC. Most tumors were in the periauricular (n = 9) and
      the frontozygomatic (n = 6) areas. Seven patients presented with facial weakness
      or paralysis. Three patients had clinically evident parotid metastasis, while 14
      patients had tumors directly invading the parotid gland. Eighteen patients had
      recurrent disease that had been treated previously with Mohs micrographic
      surgery. INTERVENTIONS: Following wide local excision of the ANMSC, 12 patients
      had resection of the lateral parotid lobe with preservation of the nerve, while
      11 required radical parotidectomy with sacrifice of 1 or more branches. Nineteen
      patients received cervical lymphadenectomy. Postoperative radiotherapy was
      administered in 19 patients. MAIN OUTCOME MEASURES: Tumor pathologic findings
      (specifically, perineural invasion of the facial nerve), locoregional control or
      recurrence, disease-free survival, disease-specific survival, and overall
      survival. RESULTS: Neurotropic spread to the facial nerve was present in 6
      patients and was more likely to occur in younger patients (51 vs 75 years, P
      =.006). Locoregional failures occurred in 9 patients following treatment.
      Patients who required parotidectomy in their surgical treatment for an ANMSC were
      more likely to have recurrent disease (P =.0002). Disease-specific and overall
      survival was 79% and 69%, respectively, at 42 months. CONCLUSIONS: Patients with
      ANMSC may require parotidectomy in the context of neurotropic spread, regional
      metastasis, or direct invasion into the parotid gland. Surgery combined with
      postoperative radiotherapy is necessary in most patients because of adverse
      clinical and pathologic findings. A systematic approach to the management of the
      parotid and facial nerve in the presence of these aggressive tumors is required.
      Despite comprehensive treatment, local recurrence of ANMSC and mortality remain
      high.

PMID- 12003583
TI  - Combined intraoral and lateral temporal approach for palatal malignancies with
      temporalis muscle reconstruction.
AB  - OBJECTIVE: To evaluate the use of a combined lateral temporal fossa and intraoral
      approach to resect palatal carcinomas and the use of a temporalis myofascial flap
      for reconstruction. DESIGN: Retrospective chart review of a case series. SETTING:
      Tertiary university referral hospital. PATIENTS: Sixteen patients underwent a
      combined approach for resection of palatal carcinoma; 5 of the 16 were
      edentulous. Six types of tumors were treated: adenoid cystic carcinoma (3
      patients), low-grade mucoepidermoid carcinoma (5 patients), squamous cell
      carcinoma (3 patients), polymorphous low-grade adenocarcinoma (2 patients),
      osteosarcoma (1 patient), ameloblastoma (1 patient), and hyalinizing clear cell
      carcinoma (1 patient). MAIN OUTCOME MEASURES: The postoperative diet, velum
      competence, flap viability, complications, and survival. RESULTS: Fifteen (94%)
      of 16 patients were able to resume their preoperative diets. No velopharyngeal
      insufficiency was encountered. All flaps survived and none required repeated
      surgical intervention. Five patients developed serous otitis media and 2 patients
      required flap revision secondary to posterior choanal obstruction. One patient
      died of complications unrelated to the procedure. CONCLUSIONS: A combined
      intraoral and lateral temporal fossa approach allows for (1) en bloc resection of
      palatal malignancies along with resection of involved pterygoid muscles, (2)
      isolation and resection of descending palatine nerves and the proximal second
      division of the trigeminal nerve, and (3) primary reconstruction of the palatal
      defect by means of the temporalis muscle rotated into the operative defect. This
      method is especially useful in treating patients with perineural spread of
      palatal carcinoma, and in those who are edentulous.

PMID- 12003584
TI  - Treatment of patients with spinal metastases from head and neck neoplasms.
AB  - BACKGROUND: Spinal metastases are uncommon in patients with advanced head and
      neck cancer. Treatment strategies in this patient group have not been defined.
      Although it has been established that neurologic dysfunction in patients with
      spinal metastases and cord compression constitutes an oncologic emergency, the
      role of surgical treatment remains controversial. OBJECTIVE: To clarify the
      treatment options in patients with head and neck cancer who develop spinal
      metastases. METHODS: The clinical course of patients seen at our institution with
      head and neck neoplasms and spinal metastases from January 1992 to January 2000
      was reviewed. RESULTS: Eleven patients were identified. Nine developed spinal
      metastases more than 3 months after the diagnosis of advanced head and neck
      cancer. The other 2 presented with synchronous spinal involvement and skull base
      neoplasms. Patients without neurologic symptoms were offered intravenous steroids
      and palliative radiation. Patients with neurologic symptoms were treated with
      either intravenous steroids and radiation or surgical decompression and spinal
      fusion. In 1 patient, no improvement occurred within the first 2 days of
      radiotherapy, and the patient underwent surgical decompression. Patients with an
      unstable spine underwent surgical decompression and spinal fusion. Patients with
      a life expectancy of more than 6 months and neurologic symptoms were offered
      surgical therapy. In the 9 patients with advanced cancer, the average survival
      time was 3 months. Two of these patients have survived longer than 6 months.
      CONCLUSIONS: We propose that surgical decompression is a viable, justifiable
      option for selected patients with advanced head and neck cancer and spinal cord
      compression. Furthermore, we recommend surgical decompression as a first option
      in patients with an unstable bony spine and/or in whom survival is expected to be
      longer than 6 months. Finally, we propose a patient management algorithm in these
      cases.

PMID- 12003585
TI  - The effect of noise exposure in the presence of canal fenestration on the
      amplitude of short-latency vestibular evoked potentials.
AB  - BACKGROUND: Exposure to high-intensity noise causes little, if any, reduction in
      vestibular function in normal animals as shown by short-latency vestibular evoked
      potentials (VsEPs). OBJECTIVE: To investigate the effect of noise exposure on
      VsEPs following fenestration of the horizontal semicircular canal. DESIGN AND
      METHODS: Psammomys obesus (fat sand rat) underwent labyrinthectomy in 1 ear,
      while the lateral semicircular canal in the other ear was fenestrated. Control
      VsEPs to linear acceleration (approximately 3g; rise time, approximately 1-2
      milliseconds) were recorded immediately after the operation. The experimental
      group animals were then subjected to loud white noise (113-dB sound pressure
      level) for 1 hour. Immediately after the noise exposure in the experimental group
      animals, VsEPs were once more recorded. RESULTS: The VsEPs in the experimental
      group animals were significantly reduced immediately following the noise
      exposure, while there was no change in the recordings from the control group
      animals (fenestrated but not noise exposed; noise exposed but not fenestrated),
      even though the noise exposure induced a mean 47-dB threshold elevation of the
      auditory brainstem response. CONCLUSIONS: The presence of the fenestration caused
      the vestibular end organs to become vulnerable to noise exposure. The
      fenestration may create a pathway enabling pressure release through the
      vestibular end organs during noise exposure, thus increasing the possibility of
      damage to the vestibular end organs. This did not occur in the intact,
      nonfenestrated animals.

PMID- 12003586
TI  - Three-dimensional imaging of the inner ear by volume-rendered reconstructions of
      magnetic resonance data.
AB  - OBJECTIVE: To evaluate 3-dimensional inner ear visualization by volume rendering
      of high-resolution magnetic resonance data in patients with clinically suspected
      inner ear abnormality. DESIGN: Prospective comparative study of different
      postprocessing techniques, based on blinded film readings. SETTING: Tertiary
      referral hospital. SUBJECTS: Fifty patients (17 females and 33 males) aged 1 to
      77 years (average age, 42 years) with sensorineural hearing loss, vertigo, and/or
      tinnitus. INTERVENTION: Postprocessing of magnetic resonance data to inner ear
      reconstructions by the use of volume rendering as well as maximum-intensity
      projection; caloric testing by electronystagmography. MAIN OUTCOME MEASURES: Film
      was read blindly by 4 radiologists using a 5-point parameter scale for image
      quality and diagnostic value. The assessibility of inner ear subsegments was
      evaluated. The specificity of volume-rendered reconstructions for detecting
      semicircular canal obliterations was assessed in a subgroup of 9 patients by
      caloric testing. The time required for data postprocessing as well as film
      reading was recorded by means of a stopwatch. RESULTS: Volume-rendered inner ear
      reconstructions were superior in image quality (P<.001), diagnostic value
      (P<.001), subsegment inner ear assessment (P<.01 to P<.001), and film reading
      time (P<.001) compared with maximum-intensity projections. The data
      postprocessing time was comparable for both techniques. Caloric weakness was
      noted in all patients assessed by electronystagmography. CONCLUSION: Volume
      rendering is the postprocessing technique of choice for 3-dimensional inner ear
      visualization, performing better than maximum-intensity projections with respect
      to various parameters.

PMID- 12003587
TI  - Serotonin reuptake inhibitors for dizziness with psychiatric symptoms.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of selective serotonin
      reuptake inhibitors (SSRIs) for the treatment of patients with dizziness and
      major or minor psychiatric symptoms, with or without neurotologic illnesses.
      DESIGN: Review of 60 consecutive cases of patients with dizziness who were
      treated with an SSRI for at least 20 weeks during the 30-month period from July
      1998 to December 2000. SETTING: Tertiary care, multidisciplinary referral center.
      PATIENTS: Sixty men and women, aged 13 to 81 years, with (1) psychogenic
      dizziness, (2) dizziness due to a neurotologic condition, as well as significant
      psychiatric symptoms, or (3) idiopathic dizziness. INTERVENTIONS: Open-label
      treatment with an SSRI titrated to 1 of 3 end points: optimal clinical benefit,
      intolerable adverse effects, or no therapeutic response. MAIN OUTCOME MEASURE:
      Change in dizziness and psychiatric symptoms measured by the 7-point, clinician
      rated, Clinical Global Impressions-Improvement Scale. RESULTS: Thirty-eight (63%)
      of 60 patients in the intent-to-treat sample and 32 (84%) of 38 patients who
      completed treatment improved substantially. The response rates did not differ
      between patients with major psychiatric disorders and those with lesser
      psychiatric symptoms. Patients whose only diagnosis was a psychiatric disorder
      and those with coexisting peripheral vestibular conditions or migraine headaches
      fared better than patients with central nervous system deficits. Before being
      treated with an SSRI, two thirds of the study patients took meclizine
      hydrochloride and/or benzodiazepines, with minimal benefit. CONCLUSIONS:
      Treatment with SSRIs relieved dizziness in patients with major or minor
      psychiatric symptoms, including those with peripheral vestibular conditions and
      migraine headaches. Patients fared far better with SSRI treatment than with
      treatment with vestibular suppressants or benzodiazepines.

PMID- 12003588
TI  - The impact of atopy on neutrophil activity in middle ear effusion from children
      and adults with chronic otitis media.
AB  - OBJECTIVE: To identify the relationship of neutrophil activity to allergy as
      reflected by the level of myeloperoxidase (MPO) in ears of atopic patients with
      chronic otitis media with effusion (OME) by objective testing. DESIGN: Evidence
      of neutrophils was measured in the effusion of atopic patients with chronic OME.
      Atopy was determined by intradermal and/or in vitro testing of allergic reaction
      to 10 inhalants, 2 molds, and 5 foods. SUBJECTS: Effusion MPO was measured
      prospectively in 138 ears from 106 consecutive patients with chronic OME.
      RESULTS: A total of 86 (81%) of 106 patients with OME tested atopic by in vitro
      or in vivo testing. Excluding 36 ears with purulence, the mean MPO level was 3132
      microg/L in 84 atopic vs 142 microg/L in 18 nonatopic ears (P<.001). A total of
      78 (90%) of 87 patients with OME were atopic. CONCLUSIONS: The surprising finding
      of marked elevation of effusion MPO in atopic patients but very low levels in
      nonatopic patients (P < .001) suggests that atopy may contribute to elevated
      levels of neutrophil activity in OME. An atopic patient may respond differently
      from a nonatopic one to the microbial or viral products of acute inflammation
      owing to the presence of primed inflammatory cells. This study provides
      confirmation on a cellular level that neutrophils are an integral part of the
      inflammatory process in OME to a disproportionate degree among atopic patients.

PMID- 12003589
TI  - Congenital high airway obstruction syndrome and airway reconstruction: an
      evolving paradigm.
AB  - OBJECTIVES: To refine the classic definition of, and provide a working definition
      for, congenital high airway obstruction syndrome (CHAOS) and to discuss the
      various aspects of long-term airway reconstruction, including the range of
      laryngeal anomalies and the various techniques for reconstruction. DESIGN:
      Retrospective chart review. PATIENTS: Four children (age range, 2-8 years) with
      CHAOS who presented to a single tertiary care children's hospital for pediatric
      airway reconstruction between 1995 and 2000. CONCLUSIONS: To date, CHAOS remains
      poorly described in the otolaryngologic literature. We propose the following
      working definition for pediatric cases of CHAOS: any neonate who needs a surgical
      airway within 1 hour of birth owing to high upper airway (ie, glottic,
      subglottic, or upper tracheal) obstruction and who cannot be tracheally intubated
      other than through a persistent tracheoesophageal fistula. Therefore, CHAOS has 3
      possible presentations: (1) complete laryngeal atresia without an esophageal
      fistula, (2) complete laryngeal atresia with a tracheoesophageal fistula, and (3)
      near-complete high upper airway obstruction. Management of the airway,
      particularly in regard to long-term reconstruction, in children with CHAOS is
      complex and challenging.

PMID- 12003590
TI  - Prevalence and risk factors for voice problems among telemarketers.
AB  - OBJECTIVES: To investigate whether there is an increased prevalence of voice
      problems among telemarketers compared with the general population and if these
      voice problems affect productivity and are associated with the presence of known
      risk factors for voice problems. DESIGN: Cross-sectional survey study. SETTINGS:
      One outbound telemarketing firm, 3 reservations firms, 1 messaging firm, 1 survey
      research firm, and 1 community college. PARTICIPANTS: Random and cluster sampling
      identified 373 employees of the 6 firms; 304 employees completed the survey. A
      convenience sample of 187 community college students similar in age, sex,
      education level, and smoking prevalence served as a control group. MAIN OUTCOME
      MEASURES: Demographic, vocational, personality, and biological risk factors for
      voice problems; symptoms of vocal attrition; and effects of symptoms on work.
      RESULTS: Telemarketers were twice as likely to report 1 or more symptoms of vocal
      attrition compared with controls after adjusting for age, sex, and smoking status
      (P<.001). Of those surveyed, 31% reported that their work was affected by an
      average of 5.0 symptoms These respondents tended to be women (P<.001) and were
      more likely to smoke (P =.02); take drying medications (P<.001); have sinus
      problems (P =.04), frequent colds (P<.001), and dry mouth (P<.001); and be
      sedentary (P<.001). CONCLUSIONS: Telemarketers have a higher prevalence of voice
      problems than the control group. These problems affect productivity and are
      associated with modifiable risk factors. Evaluation of occupational voice
      disorders must encompass all of the determinants of health status, and treatment
      must focus on modifiable risk factors, not just the reduction of occupational
      vocal load.

PMID- 12003591
TI  - The effect of growth factors on the proliferation and differentiation of human
      nasal gland cells.
AB  - OBJECTIVE: To elucidate a mechanism of proliferation and differentiation of nasal
      gland cells, we established a serum-free 3-dimensional culture system for human
      nasal gland (HNG) cells and examined the effects of epidermal growth factor,
      keratinocyte growth factor, and retinoic acid on proliferation and
      differentiation of cultured HNG cells. MATERIALS AND METHODS: Nasal polyps were
      obtained from patients undergoing endoscopic endonasal sinus surgery. The HNG
      cells were cultured under a monolayer culture and transferred to a collagen
      embedded culture using RPMI 1640 medium containing transferrin, insulin,
      hydrocortisone, retinoic acid, epidermal growth factor, and keratinocyte growth
      factor. Cell growth was measured by bromodeoxyuridine incorporation assays. To
      measure cell differentiation, the percentage of cells containing secretory
      granules, which were stained with Alcian blue in cytoplasm, was determined.
      RESULTS: In the serum-free 3-dimensional culture, the HNG cells showed ductal
      structures containing secretory products in a lumen. The addition of epidermal
      growth factor promoted the proliferation of HNG cells in its optimal
      concentrations, and keratinocyte growth factor also enhanced the proliferation of
      HNG cells. Conversely, the differentiation of HNG cells was not dependent on
      epidermal growth factor and keratinocyte growth factor. Retinoic acid suppressed
      the proliferation, but promoted the differentiation of HNG cells. CONCLUSION: Our
      culture system could be useful for studying the effects of various growth factors
      and cytokines on HNG proliferation and differentiation to better understand the
      mechanisms of growth and morphogenesis of nasal glands.

PMID- 12003592
TI  - Bacteriology of acute and chronic frontal sinusitis.
AB  - Aspirates of 15 acutely and 13 chronically infected frontal sinuses were
      processed for aerobic and anaerobic bacteria. A total of 20 isolates (1.3 per
      specimen) were recovered from the 15 cases of acute frontal sinusitis, 16 aerobic
      and facultative isolates (1.1 per specimen) and 4 anaerobic isolates (0.3 per
      specimen). Aerobic and facultative organisms alone were recovered in 13 specimens
      (87%), and mixed aerobic and anaerobic bacteria were recovered in 2 (13%). The
      predominant aerobic and facultative organisms were Haemophilus influenzae (6),
      Streptococcus pneumoniae (5), and Moraxella catarrhalis (3). A total of 32
      isolates were recovered from the 13 cases (2.5 per patient) of chronic frontal
      sinusitis, 12 aerobic and facultative isolates (0.9 per specimen) and 20
      anaerobic isolates (1.5 per specimen). Aerobic and facultative organisms only
      were recovered in 3 instances (23%), anaerobes only in 7 instances (54%), and
      mixed aerobic and anaerobic bacteria in 3 instances (23%). The predominant
      aerobic bacteria were gram-negative bacilli (H influenzae, Klebsiella pneumoniae,
      and Pseudomonas aeruginosa). The predominant anaerobes included Prevotella
      species (8), Peptostreptococcus species (6), and Fusobacterium species (4). These
      findings illustrate the microbiologic features of acute and chronic frontal
      sinusitis.

PMID- 12003593
TI  - Recurrent inner ear decompression sickness associated with a patent foramen
      ovale.
AB  - Isolated inner ear injuries occurring during shallow scuba dives are an uncommon
      manifestation of decompression sickness in recreational divers. We describe a
      patient who presented with the typical symptoms of inner ear involvement after 2
      independent dives within the decompression limits. The diver reported symptoms of
      unilateral (right-sided) hearing loss, tinnitus, and vertigo after dives to 35
      and 50 m. After treatment with hyperbaric oxygen, his symptoms completely
      resolved. To confirm the hypothesis of inner ear decompression sickness (IEDCS),
      we examined the patient for a right-to-left shunt by cranial Doppler ultrasound
      and found a patent foramen ovale. The existence of a patent foramen ovale is
      suspected to be a risk factor for developing neurological symptoms of
      decompression sickness. There was no evidence of any other risk factors, so we
      suggest that the relevant right-to-left shunt in our patient may have been the
      predisposing factor that caused the inner ear symptoms during his scuba dive.

PMID- 12003594
TI  - Headset-related sensory and motor neuropathies in image-guided sinus surgery.
AB  - Complications related to the use of image-guided systems in sinus surgery are
      fortunately rare. We report a case series of 6 patients who experienced facial
      neuropathies (both sensory and motor) related to the use of a headset for
      electromagnetic-based image-guided surgery. The auriculotemporal nerve was the
      most common sensory nerve involved, and the buccal branch of the facial nerve was
      implicated in a case of motor weakness. The cause of the complication appears to
      be a pressure neuropathy caused by a tight-fitting headset against the external
      auditory meatus and temporomandibular joint. Additional risk factors for headset
      related neuropathy may relate to body habitus, length of surgical procedure, and
      patient positioning. All patients' neuropathies resolved completely without
      intervention. Headset-related complications appear to be uncommon but may be an
      important consideration in counseling patients who are candidates for image
      guided sinus surgery.

PMID- 12003595
TI  - Clinical problem solving: pathology. Pathology quiz case 1: benign parathyroid
      cyst.

PMID- 12003596
TI  - Clinical problem solving: pathology. Pathology quiz case 2: granular cell tumor
      of the trachea.

PMID- 12003597
TI  - Clinical problem solving: radiology. Radiology quiz case 1: opacified Onodi cell.

PMID- 12003598
TI  - Clinical problem solving: radiology. Radiology quiz case 2: Lemierre syndrome.

PMID- 12003599
TI  - Marginal mandibulectomy vs segmental mandibulectomy: indications and
      controversies.

PMID- 12003600
TI  - The role of marginal mandibulectomy in the surgical management of oral cancer.

PMID- 12003601
TI  - Clinical commentary on marginal vs segmental resection of the mandible.

PMID- 12003602
TI  - Enzymatic sclerostomy: pilot human study.
AB  - OBJECTIVE: To evaluate the feasibility and safety of enzymatic sclerostomy as a
      new modality to lower intraocular pressure in patients with open-angle glaucoma.
      METHODS: This single-center, prospective, noncomparative, interventional case
      series included 15 blind symptomatic eyes of 15 patients with primary open-angle
      glaucoma. Enzymatic sclerostomy was performed with the patient under topical or
      peribulbar anesthesia. A specially designed polymethylmethacrylate enzyme
      applicator filled with a mean +/- SD of 123 +/- 13 microg of collagenase was
      introduced through a 5-mm peritomy, and affixed to the limbus by means of
      cyanoacrylate tissue glue. After 22 to 24 hours, the applicators were removed and
      the patients were followed up for 1 year. Intraocular pressure changes from
      baseline and complications related to the procedure were the main outcome
      measures. RESULTS: Controlled thinning of the treated sclera associated with
      aqueous percolation and shallow filtration bleb was seen in all eyes in the
      immediate postoperative period. The mean +/- SD intraocular pressure decreased
      from 43.5 +/- 9.8 mm Hg (while the patients were receiving a mean +/- SD of 1.75
      +/- 0.75 antiglaucoma medications) preoperatively to 24.8 +/- 10.6 mm Hg (a 43.0%
      decrease from baseline with no antiglaucoma medication) on the first
      postoperative day and to 34.8 +/- 10.5 mm Hg (a 20.0% decrease from baseline with
      no antiglaucoma medication) at the end of 1 year. Ophthalmic adverse effects were
      limited to the treated area and included immediate postoperative transient
      conjunctival reaction ranging from mild chemosis to conjunctival maceration.
      Immediate full-thickness perforation developed in 1 eye; the patient was treated
      and excluded from data analysis. Two eyes developed symptoms related to increase
      in intraocular pressure after 9 months; the patients were treated and excluded
      from further data analysis. No systemic complications were noted. CONCLUSIONS:
      Enzymatic sclerostomy demonstrated immediate and sustained intraocular pressure
      reduction and provided symptomatic relief in blind eyes with primary open-angle
      glaucoma. The procedure, however, needs further technical refinement.

PMID- 12003603
TI  - Human immunodeficiency virus infection, Bcl-2, p53 protein, and Ki-67 analysis in
      ocular surface squamous neoplasia.
AB  - OBJECTIVES: To determine the age and human immunodeficiency virus (HIV) status of
      patients with ocular surface squamous neoplasia (OSSN), and to analyze tumor
      proliferation, Bcl-2, and p53 oncoprotein expression in OSSN. METHODS: Only
      patients with histologically proved neoplasia were included in this study. The
      HIV status was obtained only with informed consent. Monoclonal antibodies to p53
      and Bcl-2 protein were used after microwave antigen retrieval to enhance
      immunohistochemical staining of the sections. Proliferation was assessed by means
      of Ki-67 antigen expression. Positive staining in each specimen was expressed as
      a percentage and graded accordingly. RESULTS: Forty-one eyes in 40 black patients
      with a mean age of 37 years were found to have OSSN. Of the 41 lesions, 35
      represented in situ or invasive carcinoma. The remaining 6 had mild or moderately
      dysplastic lesions. Seventeen patients agreed to an HIV test and, of these, 12
      (70.6%) were HIV positive. All 12 were younger than 50 years, and 11 had either
      carcinoma in situ or invasive lesions. Twenty-two of 40 lesions expressed
      significant (greater than 50% of neoplastic cells) p53 positivity, while Bcl-2
      expression was detected in 10. Ki-67 expression was low, even in the HIV-positive
      lesions. CONCLUSIONS: At our institution, OSSN occurs in young patients, many of
      whom are HIV positive. Expression of p53 is a common finding, whereas Bcl-2
      immunoexpression occurs in the minority of cases. Ki-67 analysis showed that OSSN
      is a slow-growing tumor, even in the presence of HIV infection.

PMID- 12003604
TI  - Management of vitreoretinal complications in eyes with permanent
      keratoprosthesis.
AB  - OBJECTIVES: To evaluate the spectrum and treatment of posterior segment
      complications in eyes that had undergone successful keratoprosthesis (KPro)
      placement and to determine whether transeyelid vitrectomy techniques could be
      effectively used in eyes otherwise vulnerable to surface exposure. DESIGN: In the
      last 10 years, 110 patients received a Dohlman-Doane KPro at the Massachusetts
      Eye and Ear Infirmary, Boston. We evaluated 22 eyes in 18 patients that required
      subsequent vitreoretinal surgery to treat posterior segment complications. One
      surgeon using modified vitreoretinal techniques, as described below, performed
      all vitreoretinal procedures. RESULTS: The posterior segment complications
      included 6 cases of retro-KPro membranes, 13 cases of retinal detachments, and 5
      cases of isolated vitreous opacity. All 6 retro-KPro membranes were effectively
      removed by vitrectomy without significant complication and 3 of these patients
      enjoyed improvement of visual acuity of at least 5 Snellen lines. Of 13 cases of
      retinal detachment, 6 patients had some improvement in visual acuity, 5 showed no
      appreciable change, and 2 had some decline in the final visual acuity. In all 5
      cases of isolated vitreous opacity, the media was effectively cleared with pars
      plana vitrectomy. Three patients enjoyed improvement of visual acuity of at least
      3 Snellen lines. Four cases of transeyelid vitrectomy were attempted and
      anatomical success was achieved in all 4 and vision improved in 3 of these
      patients. No special surgical complications were encountered in any of the 22
      eyes as a result of these modified surgical techniques. MAIN OUTCOME MEASURES:
      Best preoperative and postoperative visual acuity and anatomical success were
      evaluated in relation to the preoperative posterior segment complication.
      CONCLUSIONS: Modified vitreoretinal surgical techniques can be effectively and
      safely used to treat posterior segment complications in patients with KPro
      devices. Retro-KPro membranes and other vitreous opacities were the most amenable
      to treatment. Retinal complications posed a special challenge. However, all of
      these cases highlight that modified vitrectomy techniques can be used in eyes
      with permanent KPro devices. These techniques can be performed without additional
      risk to the eye. Additionally, we demonstrated that transeyelid vitrectomy
      techniques could be used effectively to manage complications in eyes with severe
      ocular surface disease without undue exposure of vulnerable tissues.

PMID- 12003605
TI  - Clinical variations in assessment of bull's-eye maculopathy.
AB  - OBJECTIVES: To evaluate the phenotypic variation in bull's-eye maculopathy and
      seek possible correlations between functional loss and clinical appearance.
      METHODS: From January 1, 1999, to September 30, 2000, we prospectively examined
      patients with bull's-eye lesions. Age of onset, duration of symptoms, visual
      acuity, clinical appearance, and autofluorescence images were recorded, the area
      of atrophy measured, and electrophysiologic investigations performed. RESULTS:
      Forty-seven patients, including 6 sibling pairs, met the study entry criteria. On
      the basis of autofluorescence imaging, 3 distinct groups were identified. Group 1
      showed a distinct ring of increased autofluorescence surrounding an area of
      decreased autofluorescence. In group 2, the ring of increased autofluorescence
      was not present. Group 3 displayed a speckled appearance within the affected
      area. All patients had evidence of central sparing in an area of centrally
      increased autofluorescence. There was significant correlation with the age of
      onset, visual acuity, and duration of disease. Electrophysiologic tests revealed
      that 28 patients had macular dysfunction only, 14 had cone-rod dystrophy, 3 had
      rod-cone dystrophy, and only 2 (monozygotic twins) had cone dystrophy. The
      correlation between electrophysiologic and autofluorescence data was poor. The
      sibling pairs had concordant autofluorescence appearance, but electrophysiologic
      grouping differed in 2 pairs. CONCLUSIONS: Bull's-eye maculopathy represents a
      heterogeneous group of disorders. The clinical appearance was not helpful in
      assessing the degree of retinal dysfunction. The difference in qualitative
      characteristics of functional loss between siblings implies that these attributes
      do not necessarily reflect the influence of the primary mutation.

PMID- 12003606
TI  - Symmetry of bilateral lesions in geographic atrophy in patients with age-related
      macular degeneration.
AB  - BACKGROUND: As a cause for severe visual loss, geographic atrophy of the retinal
      pigment epithelium is about half as common as choroidal neovascularization in
      patients with advanced age-related macular degeneration. To assess symmetry, we
      determined intraindividual variations of various features of bilateral geographic
      atrophy in patients with atrophic age-related macular degeneration in a cross
      sectional study. METHODS: Patients were examined with the use of a confocal
      scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg
      Engineering, Heidelberg, Germany). Digital infrared reflection images
      (excitation, 830 nm) and fundus autofluorescence images (excitation, 488 nm) were
      recorded. The eyes of each patient were compared regarding number, size, and
      convex hull of the atrophic areas with the use of image analysis software and
      with respect to fundus autofluorescence changes in the junctional zone. RESULTS:
      Seventy-two patients (mean +/- SD age, 76.3 +/- 7.9 years) were examined. The
      number of atrophic areas ranged from 1 to 23 (mean +/- SD, 4.9 +/- 4.6); the size
      of geographic atrophy, from 0.18 to 30.20 (mean +/- SD, 7.0 +/- 6.6) mm(2); and
      the size of the convex hull, from 0.18 to 39.20 (mean +/- SD, 11.7 +/- 8.4)
      mm(2). No statistically significant difference was found when comparing these
      variables between each left and right eye: number, P =.62; size, P =.81; and
      convex hull, P =.78. Identical patterns of fundus autofluorescence were observed
      in 43 (80%) of 54 patients. CONCLUSIONS: There is intraindividual symmetry in
      eyes with bilateral geographic atrophy in the presence of a wide range of
      interindividual variability. The findings are in accordance with the view that
      age-related macular degeneration is not merely the result of a nonspecific aging
      process. Symmetric manifestations, rather, reflect specific individual
      determinants in the pathogenesis and manifestation of the disease.

PMID- 12003607
TI  - Limited macular translocation for atrophic maculopathy.
AB  - OBJECTIVES: To report visual improvement following bilateral limited macular
      translocation for a patient with atrophic macular disease, and to discuss issues
      related to the selection of potential candidates for this technique. DESIGN: Case
      report. RESULTS: A 78-year-old woman with bilateral atrophic maculopathy and no
      choroidal neovascularization had slowly progressive loss of visual acuity for at
      least 17 months in the right eye and 25 months in the left eye. She underwent
      bilateral limited macular translocation, using scleral infolding in the right eye
      and scleral outpouching in the left eye. Following translocation of her maculae,
      her best-corrected visual acuity improved from 20/200 to 20/30 OD and from 20/180
      to 20/100 OS. She remained stable during 30 months of follow-up for the right eye
      and 22 months of follow-up for the left eye. CONCLUSION: Macular translocation
      may allow visual recovery in selected patients with atrophic maculopathy, even
      after a prolonged period of poor vision.

PMID- 12003608
TI  - Multicenter trial of cryotherapy for retinopathy of prematurity: natural history
      ROP: ocular outcome at 5(1/2) years in premature infants with birth weights less
      than 1251 g.
AB  - OBJECTIVE: To present ophthalmological outcome data at 5(1/2) years after full
      term from a natural history cohort of infants who had a birth weight less than
      1251 g and were enrolled at 5 centers of the Multicenter Trial of Cryotherapy for
      Retinopathy of Prematurity (ROP), including eyes without ROP and with a full
      range of ROP severity. DESIGN: Of the 1199 surviving children in the cohort, 1068
      (89.1%) were examined. Study-certified ophthalmologists assessed ROP residua and
      conducted cycloplegic refractions. Visual acuity was measured by study-trained
      testers using the Early Treatment for Diabetic Retinopathy Study charts. Eyes
      that had developed ROP were categorized by the lowest (most posterior) zone and
      highest (most severe) stage reached during the acute phase of the disease. No
      eyes that received cryotherapy are included; data analysis included one untreated
      eye per patient. Fundus outcomes were classified as "unfavorable" if there was
      macular compromise by retinal folding (more severe than ectopia) or stage 4B or 5
      retinal detachment. Visual acuity outcomes of 20/200 or worse were classified as
      unfavorable. RESULTS: Unfavorable fundus structural outcome occurred in 33 (3.1%)
      of the 1068 eyes; all 33 eyes had a history of severe ROP. Specifically,
      unfavorable fundus structure occurred in 62.5% (10/16) of eyes with zone I ROP
      and in 44.2% (23/52) of eyes with zone II ROP, stage 3+ disease involving more
      than six 30 degrees -sectors. There were no unfavorable fundus outcomes among
      eyes that had fewer than 7 clock-hours of stage 3+ ROP in zone II in this cohort.
      Snellen visual acuity was tested in 1059 eyes, and 5.1% were unfavorable at
      20/200 or worse; these unfavorable outcomes were correlated with more severe ROP.
      In eyes that had zone I ROP, 68.8% (11/16) had unfavorable acuity, and for eyes
      that had zone II ROP, 7.5% (36/481) had unfavorable acuity results. For eyes with
      ROP observed only in zone III, 1.8% (2/110) had unfavorable acuity of 20/200 or
      worse. CONCLUSIONS: Premature infants with birth weights less than 1251 g seldom
      have poor structural and functional outcomes (3.1% and 5.1%, respectively). All
      unfavorable fundus structural outcomes and nearly all unfavorable acuity outcomes
      occurred in eyes with zone I ROP or zone II ROP involving more than 6 sectors of
      stage 3+ disease.

PMID- 12003609
TI  - Association between sleep apnea syndrome and nonarteritic anterior ischemic optic
      neuropathy.
AB  - OBJECTIVE: To determine if patients with nonarteritic ischemic optic neuropathy
      (NAION) have sleep apnea syndrome (SAS), an entity characterized by repetitive
      upper airway obstructions during sleep, inducing hypoxia and sleep disruption.
      METHODS: We recruited 17 patients with NAION and 17 age- and sex-matched controls
      from patients referred for treatment because of suspected restless legs syndrome.
      We performed overnight polysomnography and determined the respiratory disturbance
      index during night sleep, a value used to diagnose and grade SAS. We compared the
      proportions of patients with SAS among patients with NAION and matched controls
      using the chi(2) test. Additionally, we compared the proportions of patients with
      SAS among patients with NAION and a large SAS prevalence study using the binomial
      test. RESULTS: Twelve (71%) of 17 patients with NAION had SAS. According to the
      respiratory disturbance index, 4 patients (24%) had mild, 4 patients (24%) had
      moderate, and 4 patients (24%) had severe SAS. Only 3 (18%) of 17 controls had
      SAS (P =.005). In the 45- to 64-year age group, 4 (50%) of 8 patients with NAION
      had SAS; 51 (11.9%) of 430 of the random sample in the prevalence study had SAS
      (P =.005). In the group older than 64 years, 8 (89%) of 9 patients with NAION had
      SAS; 18 (24%) of 75 of the random sample in the prevalence study had SAS
      (P<.001). CONCLUSIONS: We found a high prevalence of SAS in patients with NAION,
      which supports previous case reports suggesting that such an association exists.
      This association may explain why approximately 75% of all patients with NAION
      discover visual loss on first awakening or when they first use vision critically
      after sleeping. Our findings indicate that SAS may play an important role in the
      pathogenesis of NAION.

PMID- 12003610
TI  - Toxicity and dose-response studies of 1alpha-hydroxyvitamin D2 in a
      retinoblastoma xenograft model.
AB  - BACKGROUND: Although calcitriol (1,25-dihydroxycholecalciferol) and vitamin D(2)
      inhibit retinoblastoma growth in the athymic (nude) mouse xenograft (Y-79 cell
      line) model of retinoblastoma, they can cause severe toxicity. OBJECTIVE: To
      examine the toxicity of and dose-dependent response for the inhibition of tumor
      growth for 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)), an analogue with reduced
      systemic toxicity, in the athymic Y-79 mouse model. METHODS: Mice were randomized
      into treatment and control groups for 5-week toxicity and dose-response studies.
      Treatment was via oral gavage 5 times per week. Dose-response studies measured
      tumor inhibition and drug serum levels. Tumor size and body weight were measured
      weekly together with various criteria for toxicity. Animals were euthanized at
      the end of the treatment period. Tumors and kidneys were harvested, and serum was
      analyzed for calcium and drug levels. RESULTS: Doses of 0.1 to 1.2 microg/d were
      selected on the basis of toxicity studies for the dose-response trial. Tumor
      weight and volume in the 0.2-microg and 0.3-microg doses were significantly lower
      than in controls. Mortality rates and kidney calcification in mice treated with
      doses of 0.1 to 0.3 microg were lower than those observed in studies of
      calcitriol and vitamin D(2). CONCLUSION: A vitamin D analogue, 1alpha-OH-D(2),
      inhibits tumor growth in this xenograft model of retinoblastoma with less
      toxicity than calcitriol and vitamin D(2).

PMID- 12003611
TI  - Causes of incident visual impairment: the Blue Mountains Eye Study.
AB  - OBJECTIVE: To describe the causes of 5-year incident visual impairment and
      doubling of the visual angle in a population-based cohort. METHODS: Of the 3654
      participants aged older than 50 years who participated in the Blue Mountains Eye
      Study (BMES I, 1992-1994), 543 died and 2335 were reexamined between 1997 and
      1999 (BMES II). Visual acuity was measured using a logMAR chart before and after
      refraction. Pupils were dilated, and a detailed eye examination was performed.
      For participants with incident visual impairment or doubling of the visual angle,
      an ophthalmologist attributed and proportioned causes. Primary causes were
      defined as those responsible for 50% or more of the impairment. RESULTS: After
      refractive correction, the proportion of incident bilateral impairment worse than
      20/40, worse than 20/70, and worse than 20/200 that were caused primarily by
      cataract decreased from 51.4% (n = 19) to 40.0% (n = 6) to 0%; while the
      proportion of cases caused primarily by age-related maculopathy increased from
      24.3% (n = 9) to 33.3% (n = 5) to 100.0% (n = 2). Similarly, the corresponding
      proportions of incident unilateral impairment caused primarily by cataract
      decreased from 53.7% (n = 72) to 36.9% (n = 31) to 13.6% (n = 6); meanwhile, the
      proportion of cases caused primarily by age-related maculopathy increased from
      19.4% (n = 26) to 32.1% (n = 27) to 54.5% (n = 24). The proportions of persons
      with incident bilateral impairment worse than 20/40, worse than 20/70, and worse
      than 20/200 that could be improved with refraction were 79.4% (n = 143), 73.6% (n
      = 42), and 0%, respectively. The corresponding proportions of incident unilateral
      impairment improved by refraction were 66.7% (n = 269), 59.0% (n = 121), and
      21.4% (n = 12). CONCLUSION: This study has documented the 5-year incidence and
      causes of visual impairment in an older Australian population.

PMID- 12003612
TI  - Near-work activity, night-lights, and myopia in the Singapore-China study.
AB  - OBJECTIVE: To investigate the relationship among near-work activity, night
      lights, and myopia in schoolchildren in Singapore and Xiamen, China. METHODS: The
      refractive error and ocular dimensions of 957 Chinese schoolchildren aged 7 to 9
      years in Singapore and Xiamen, China, were determined using cycloplegic
      autorefraction and A-scan ultrasound biometry. Information on near-work activity
      (number of books read per week, reading in hours per day) and night-light use
      before age 2 years was obtained. RESULTS: The prevalence rate of myopia was 36.7%
      (95% confidence interval [CI], 33.0%-40.3%) in Singapore and 18.5% (95% CI, 14.0%
      23.1%) in Xiamen, China. The crude odds ratio (OR) of higher myopia (at least 
      3.0 diopters) for children who read more than 2 books per week was 3.50 (95% CI,
      2.15-5.70). In a multivariate logistic regression model, the OR of higher myopia
      for children who read more was 2.81 (95% CI, 1.69-4.69), adjusted for age, night
      light use, parental myopia, and country, whereas there was no association between
      night-light use before age 2 years and higher myopia (OR, 1.54; 95% CI, 0.92
      2.58), after controlling for age, books read per week, parental myopia, and
      country. MAIN OUTCOME MEASURES: The ORs of higher myopia for children who read
      more and children who are exposed to night-lights before age 2 years.
      CONCLUSIONS: Reading (number of books per week) may be associated with higher
      myopia in Chinese schoolchildren. However, night-light use does not seem to be
      related to higher myopia.

PMID- 12003613
TI  - James Thurber and the problems of sympathetic ophthalmia.

PMID- 12003614
TI  - A need for innovation in glaucoma surgery.

PMID- 12003615
TI  - A worm can be monkey business.

PMID- 12003616
TI  - Effects of the pulsed electron avalanche knife on retinal tissue.
AB  - OBJECTIVES: To evaluate the precision of retinal tissue dissection by the pulsed
      electron avalanche knife (PEAK) and to assess possible toxic effects from this
      device. METHODS: To demonstrate precision of cutting, bovine retina (in vitro)
      and rabbit retina (in vivo) were incised with the PEAK. Samples were examined by
      scanning electron microscopy and histologic examination (light microscopy). To
      evaluate possible toxic effects in rabbit eyes, 30 000 pulses were delivered into
      the vitreous 1 cm above the retina. Histologic examinations and
      electroretinography were performed at intervals up to 1 month after exposure.
      RESULTS: Cuts in postmortem bovine retina showed extremely sharp edges with no
      signs of thermal damage. Full-thickness cuts in living attached rabbit retina
      were similarly sharp and were typically less than 100 microm wide. No signs of
      retinal toxic effects were detected by histologic examination or
      electroretinography. CONCLUSIONS: The PEAK is capable of precise cutting through
      retinal tissue, and there are no demonstrable retinal toxic effects from its use.
      The precision and tractionless nature of PEAK cutting offers advantages over
      mechanical tools and laser-based instrumentation. We believe this new device will
      prove useful in a variety of vitreoretinal surgical applications.

PMID- 12003617
TI  - Human subconjunctival infection of Macacanema formosana: the first case of human
      infection reported worldwide.

PMID- 12003618
TI  - Merkel cell carcinoma of the eyelid with a positive sentinel node.

PMID- 12003619
TI  - The effect of transpupillary thermotherapy on the human macula.

PMID- 12003620
TI  - Malignant peripheral nerve sheath tumor in the orbit of a child with acute
      proptosis.

PMID- 12003621
TI  - Ocular findings in spinocerebellar ataxia 7.

PMID- 12003622
TI  - Acquired retinal myelination in neurofibromatosis 1.

PMID- 12003623
TI  - Bilateral giant macular holes with excellent visual function.

PMID- 12003624
TI  - Primary aberrant oculomotor nerve regeneration from a posterior communicating
      artery aneurysm.

PMID- 12003625
TI  - Unilateral mydriasis associated with exposure to flea spray.

PMID- 12003626
TI  - Acute psychosis following the use of topical ciprofloxacin.

PMID- 12003627
TI  - Here's egg in your eye: an unusual penetrating eye injury.

PMID- 12003628
TI  - Primary conjunctival rhabdomyosarcoma.

PMID- 12003629
TI  - Vitreomacular traction syndrome with extensively myelinated nerve fibers.

PMID- 12003630
TI  - The COMS: why was it not stopped sooner?

PMID- 12003632
TI  - Subretinal fluid in optic disc edema.

PMID- 12003634
TI  - A false use of "true color".

PMID- 12003636
TI  - Imaging to detect metastases from malignant uveal melanoma.

PMID- 12003637
TI  - Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy
      in cancer.
AB  - Human 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a
      highly glycosylated protein expressed by trophoblast and a few specialized adult
      epithelia. Up-regulation of 5T4 expression in some cancers is associated with
      poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can
      alter their morphology and motility, supporting a role for such functions in
      cancer and development. A murine model to study 5T4 biology and tumour immunology
      would be useful. The production of m5T4-specific antibodies, their use in
      establishing transfected cells and documenting their biological properties in
      vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules
      by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was
      isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen
      is a 72 kDa glycoprotein (immunoprecipitation and Western blot analysis) and
      exhibits punctate cell surface expression, dependent upon the integrity of the
      actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10
      melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is
      characterized by a spindle-like morphology, increased motility, and reduced
      adhesion and proliferation rate. Immunohistochemical analysis of adult mouse
      tissues shows a restricted pattern of expression similar to that of human 5T4
      antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are
      now being used to explore novel immunotherapies in pre-clinical models and the
      biology of 5T4 in development.

PMID- 12003638
TI  - Catalytic reaction profile for NADH-dependent reduction of aromatic aldehydes by
      xylose reductase from Candida tenuis.
AB  - Kinetic substituent effects have been used to examine the catalytic reaction
      profile of xylose reductase from the yeast Candida tenuis, a representative
      aldo/keto reductase of primary carbohydrate metabolism. Michaelis-Menten
      parameters (k(cat) and K(m)) for NADH-dependent enzymic aldehyde reductions have
      been determined using a homologous series of benzaldehyde derivatives in which
      substituents in meta and para positions were employed to systematically perturb
      the properties of the reactive carbonyl group. Kinetic isotope effects (KIEs) on
      k(cat) and k(cat)/K(m) for enzymic reactions with meta-substituted benzaldehydes
      have been obtained by using NADH (2)H-labelled in the pro-R C4-H position, and
      equilibrium constants for the conversion of these aldehydes into the
      corresponding alcohols (K(eq)) have been measured in the presence of NAD(H) and
      enzyme. Aldehyde dissociation constants (K(d)) and the hydride transfer rate
      constant (k(7)) have been calculated from steady-state rate and KIE data.
      Quantitative structure-activity relationship analysis was used to factor the
      observed substituent dependence of k(cat)/K(m) into a major electronic effect and
      a productive positional effect of the para substituent. k(cat)/K(m) (after
      correction for substituent position) and K(eq) obeyed log-linear correlations
      over the substituent parameter, Hammett sigma, giving identical slope values
      (rho) of +1.4 to +1.7, whereas the same Hammett plot for logK(d) yielded rho=
      1.5. This leads to the conclusion that electron-withdrawing substituents
      facilitate the reaction and increase binding to about the same extent. KIE values
      for k(cat) (1.8) and k(cat)/K(m) (2.7), and likewise k(7), showed no substituent
      dependence. Therefore, irrespective of the observed changes in reactivity over
      the substrate series studied no shift in the character of the rate-limiting
      transition state of hydride transfer occurred. The signs and magnitudes of rho
      values suggest this transition state to be product-like in terms of charge
      development at the reactive carbon. Structure-reactivity correlations reveal
      active-site homologies among NADPH-specific and dual NADPH/NADH-specific yeast
      xylose reductases and across two aldo/keto reductase families in spite of the
      phylogenetic separation of the host organisms producing xylose reductase (family
      2B) and aldehyde reductase (family 1A).

PMID- 12003639
TI  - Interactive decision support in hepatic surgery.
AB  - BACKGROUND: Hepatic surgery is characterized by complicated operations with a
      significant peri- and postoperative risk for the patient. We developed a web
      based, high-granular research database for comprehensive documentation of all
      relevant variables to evaluate new surgical techniques. METHODS: To integrate
      this research system into the clinical setting, we designed an interactive
      decision support component. The objective is to provide relevant information for
      the surgeon and the patient to assess preoperatively the risk of a specific
      surgical procedure. Based on five established predictors of patient outcomes, the
      risk assessment tool searches for similar cases in the database and aggregates
      the information to estimate the risk for an individual patient. RESULTS: The
      physician can verify the analysis and exclude manually non-matching cases
      according to his expertise. The analysis is visualized by means of a Kaplan-Meier
      plot. To evaluate the decision support component we analyzed data on 165 patients
      diagnosed with hepatocellular carcinoma (period 1996-2000). The similarity search
      provides a two-peak distribution indicating there are groups of similar patients
      and singular cases which are quite different to the average. The results of the
      risk estimation are consistent with the observed survival data, but must be
      interpreted with caution because of the limited number of matching reference
      cases. CONCLUSION: Critical issues for the decision support system are clinical
      integration, a transparent and reliable knowledge base and user feedback.

PMID- 12003640
TI  - An innovative approach to developing the reflective skills of medical students.
AB  - BACKGROUND: Development of the reflective skills of medical students is an
      acknowledged objective of medical education. DESCRIPTION: Description of an
      educational exercise which uses an email-based process for developing the
      reflective skills of undergraduate medical students. Student quotations
      illustrate learning outcomes qualitatively. DISCUSSION: The process described is
      immediate, direct, linked to learning objectives, enables rapid responses to be
      given to the students individually, and is followed by group sharing of learning.
      It provides a rigorous and robust feedback loop for students. It is relatively
      economic for teachers and incidentally benefits curriculum design and evolution.
      The approach supports development of a reflective approach to learning.

PMID- 12003641
TI  - Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1)
      in human type 2 diabetes.
AB  - BACKGROUND: It has become increasingly clear that beta-cell failure plays a
      critical role in the pathogenesis of type 2 diabetes. Free-radical mediated beta
      cell damage has been intensively studied in type 1 diabetes, but not in human
      type 2 diabetes. Therefore, we studied the protein expression of the DNA repair
      enzyme Ogg1 in pancreases from type 2 diabetics. Ogg1 was studied because it is
      the major enzyme involved in repairing 7,8-dihydro-8-oxoguanosine DNA adducts, a
      lesion previously observed in a rat model of type 2 diabetes. Moreover, in a gene
      expression screen, Ogg1 was over-expressed in islets from a human type 2
      diabetic. METHODS: Immunofluorescent staining of Ogg1 was performed on pancreatic
      specimens from healthy controls and patients with diabetes for 2-23 years. The
      intensity and islet area stained for Ogg1 was evaluated by semi-quantitative
      scoring. RESULTS: Both the intensity and the area of islet Ogg1 staining were
      significantly increased in islets from the type 2 diabetic subjects compared to
      the healthy controls. A correlation between increased Ogg1 fluorescent staining
      intensity and duration of diabetes was also found. Most of the staining observed
      was cytoplasmic, suggesting that mitochondrial Ogg1 accounts primarily for the
      increased Ogg1 expression. CONCLUSION: We conclude that oxidative stress related
      DNA damage may be a novel important factor in the pathogenesis of human type 2
      diabetes. An increase of Ogg1 in islet cell mitochondria is consistent with a
      model in which hyperglycemia and consequent increased beta-cell oxidative
      metabolism lead to DNA damage and the induction of Ogg1 expression.

PMID- 12003642
TI  - Protein encapsulation in liposomes: efficiency depends on interactions between
      protein and phospholipid bilayer.
AB  - BACKGROUND: We investigated the encapsulation mechanism of enzymes into
      liposomes. The existing protocols to achieve high encapsulation efficiencies are
      basically optimized for chemically stable molecules. Enzymes, however, are
      fragile and encapsulation requires in addition the preservation of their
      functionality. Using acetylcholinesterase as a model, we found that most
      protocols lead to a rapid denaturation of the enzyme with loss in the
      functionality and therefore inappropriate for such an application. The most
      appropriate method is based on lipid film hydration but had a very low
      efficiency. RESULTS: To improve it and to propose a standard procedure for enzyme
      encapsulation, we separate each step and we studied the effect of each parameter
      on encapsulation: lipid and buffer composition and effect of the different
      physical treatment as freeze-thaw cycle or liposomes extrusion. We found that by
      increasing the lipid concentration, increasing the number of freeze-thaw cycles
      and enhancing the interactions of the enzyme with the liposome lipid surface more
      than 40% of the initial total activity can be encapsulated. CONCLUSION: We
      propose here an optimized procedure to encapsulate fragile enzymes into
      liposomes. Optimal encapsulation is achieved by induction of a specific
      interaction between the enzyme and the lipid surface.

PMID- 12003643
TI  - Jejunum free flap in hypopharynx reconstruction: case series.
AB  - BACKGROUND: Surgical treatment of hypopharyngeal cancers with extension to the
      retrocricoid region generally requires a circumferential pharyngolaryngectomy
      followed by a reconstruction of the removed segment of the upper digestive tract.
      Historically, many techniques have been used in order to achieve a safe and
      functional reconstruction. Jejunum interposition is generally considered the best
      reconstructive technique. METHODS: This study examines the details of the
      surgical technique, the complications, the oncological and the functional results
      in a series of 29 consecutive patients submitted to circumferential
      pharyngoesophageal resection for advanced hypopharyngeal cancer followed by
      reconstruction with a free flap of jejunum. RESULTS: Three of the transplants
      failed because of venous thrombosis. The overall success rate was 90%. There were
      no general complications. A good swallowing has been preserved in all our
      patients. All our patients where a phonatory prosthesis was positioned (20/29)
      were able to achieve speech following speech therapy and all were satisfied with
      their own capacity to communicate. CONCLUSIONS: The prognosis of hypopharyngeal
      tumours (18-40% at 5 years) remains poor, but jejunum autografts are being shown
      to be an excellent choice for the reconstruction of the cervical hypopharyngo
      oesophagus offering the patient fast rehabilitation and a reasonable quality of
      survival. Our experience confirm that this kind of reconstruction is safe with a
      good results in improving oncologic controls and restoring a good quality of
      life.

PMID- 12003644
TI  - Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF
      kappaB.
AB  - BACKGROUND: Endothelial MAdCAM-1 (mucosal addressin cell adhesion molecule-1)
      expression is associated with the oxidant-dependent induction and progress of
      inflammatory bowel disease (IBD). Melatonin, a relatively safe, potent
      antioxidant, has shown efficacy in several chronic injury models may limit MAdCAM
      1 expression and therefore have a therapeutic use in IBD. METHODS: We examined
      how different doses of melatonin reduced endothelial MAdCAM-1 induced by TNF-a in
      an in vitro model of lymphatic endothelium. Endothelial monolayers were
      pretreated with melatonin prior to, and during an exposure, to TNF-a (1 ng/ml, 24
      h), and MAdCAM-1 expression measured by immunoblotting. RESULTS: MAdCAM-1 was
      induced by TNF-a. Melatonin at concentrations over 100 microm (10(-4) M)
      significantly attenuated MAdCAM-1 expression and was maximal at 1 mM.
      CONCLUSIONS: Our data indicate that melatonin may exert therapeutic activity in
      IBD through its ability to inhibit NF-kappaB dependent induction of MAdCAM-1.

PMID- 12003646
TI  - Infant feeding indicators for use in emergencies: an analysis of current
      recommendations and practice.
AB  - OBJECTIVE: To assess the applicability and use of infant nutrition and health
      indicators during emergencies. DESIGN: Indicators recommended by international
      health and nutrition organisations for assessing infant feeding practice were
      compiled and analysed to evaluate their consistency and applicability for use in
      surveys of emergency-affected populations. These indicators included measures of
      breast-feeding status, use of artificial feeding, anthropometric status and
      morbidity. Health and nutrition surveys performed on the resident or refugee
      population of Kosovo during the years 1996-1999 were then reviewed and the use of
      infant feeding and morbidity indicators were compared. RESULTS: A number of
      recommended indicators exist for assessing infant and child feeding practice
      which have been generated by different international organisations. A comparison
      of these indicators revealed a number of inconsistencies, both in target
      population and measurement method. Their use during the Kosovo crisis was
      likewise inconsistent and prevented conclusions being drawn about the
      effectiveness of the international response in protecting infant health and
      nutrition. CONCLUSIONS: Standard indicators need to be agreed and promoted for
      use during surveys of emergency-affected populations. Failure to do so will lead
      to a continued inability to monitor the health and nutrition of infants at a
      population level during international relief operations.

PMID- 12003647
TI  - Food security and nutrition -- the Ethiopian case for action.
AB  - OBJECTIVE: To assess the 1999-2000 food security situation and the food relief
      programmes in Ethiopia, and evaluate the need for a national food and nutrition
      policy. DESIGN: A systematic search of data sources from the Ethiopian Disaster
      Prevention and Preparedness Commission (DPPC), the Ethiopian Central Statistical
      Authority, the World Food Programme (WFP) and United Nations Children's Fund
      (UNICEF), the bibliographic database Medline and direct contacts with
      associations, institutions and people concerned with food security in Ethiopia.
      SETTING: Consultations to WFP Ethiopia. RESULTS: Food availability was severely
      restricted due to recurrent disasters such as drought, flood, war and a lack of
      diversity of food items. Food accessibility was limited due to a weak subsistence
      agriculture-based economy, depletion of assets, absence of income diversity and a
      lack of alternative coping mechanisms. Food intake adequacy was rarely achieved
      due to food shortages, improper diet and poor sanitary conditions. There was a
      lack of early warning data to monitor food security indicators. Food aid
      programmes did not meet the requirements for food quantities and composition, and
      faced major obstacles in logistics and targeting of the vulnerable population.
      CONCLUSIONS: Improvements in food security and the eradication of famine will
      require investment in sustainable projects. There is an immediate need for better
      planning and targeting of food aid and a national food security monitoring
      system. A national food and nutrition policy is recommended, focusing both on
      relief efforts and on underlying factors contributing to the famine.

PMID- 12003648
TI  - Prevalence of household food poverty in South Africa: results from a large,
      nationally representative survey.
AB  - OBJECTIVES: Household food insecurity is a major determinant of undernutrition,
      yet there is little information on its prevalence in the South African
      population. This paper assesses household food insecurity in South Africa using a
      quantitative and objective measure, known as food poverty, and provides
      prevalence estimates by geographic area and socio-economic condition. DESIGN:
      Secondary data analysis combining two sources: Statistics South Africa's
      household-based 1995 Income and Expenditure Survey; and the University of Port
      Elizabeth's Household Subsistence Level series, a nationally-conducted, market
      based survey. SETTING: South Africa. SUBJECTS: A nationally representative sample
      of the entire country - stratified by race, province, and urban and non-urban
      areas - consisting of 28 704 households. RESULTS: A household is defined to be in
      food poverty when monthly food spending is less than the cost of a nutritionally
      adequate very low-cost diet. The prevalence of food poverty in South Africa in
      1995 was 43%. Food poverty rates were highest among households headed by
      Africans, followed by coloureds, Indians and whites. Higher food poverty rates
      were found with decreasing income, increasing household size, and among
      households in rural areas or those headed by females. CONCLUSIONS: The widespread
      nature of household food insecurity in South Africa is documented here.
      Prevalence rates by geographic and socio-economic breakdown provide the means for
      targeting of nutritional interventions and for monitoring progress in this field.
      The corroboration of these findings with both internal validation measures and
      external sources suggests that food poverty is a useful, objective measure of
      household food insecurity.

PMID- 12003649
TI  - The effects of birth weight and postnatal linear growth retardation on body mass
      index, fatness and fat distribution in mid and late childhood.
AB  - OBJECTIVE: To determine the effects of birth weight and early childhood stunting
      on body mass index (BMI), body fat and fat distribution at ages 7 and 11 years,
      and the change from 7 to 11 years. DESIGN: Prospective cohort study SETTING:
      Kingston, Jamaica. SUBJECTS: One hundred and sixteen stunted children (height-for
      age below two standard deviations (<-2SD) of the National Center for Health
      Statistics (NCHS) references) and 190 non-stunted children (height-for-age > 
      1SD), identified at age 9-24 months. The stunted group was divided into a
      previously stunted group (height-for-age at 11 years >or= -1SD) and a chronically
      stunted group (height-for-age < -1SD). RESULTS: Birth weight was positively
      related to the children's BMI but not to measures of body fat. Birth weight was
      negatively associated with the subscapular/triceps skinfold (SSF/TSF) ratio at
      age 11 years, and to the change between 7 and 11 years. Controlling for birth
      weight, the chronically stunted group remained significantly smaller than the non
      stunted children at both ages and increased less from 7 to 11 years in all
      measures except the SSF/TSF ratio, which was significantly greater at age 7
      years. The previously stunted group had significantly lower BMI and percentage
      body fat at age 7 years than the non-stunted group. Change from 7 to 11 years was
      not significantly different from that of the non-stunted group except for a
      smaller increase in TSF. At age 11 years they had significantly lower TSF and
      percentage body fat. CONCLUSIONS: Children stunted in early childhood had less
      fat and lower BMI than non-stunted children but had a more central fat
      distribution that was partially explained by their lower birth weights. The
      association between birth weight and central fat distribution developed between 7
      and 11 years.

PMID- 12003650
TI  - Food security in the Baltic Republics.
AB  - OBJECTIVES: Food insecurity has become an important issue in many countries of
      the former Soviet Union following the transition to a market economy. This study
      examined three aspects of food security in the Baltic Republics: reasons for
      choosing foods; level of dependence on home-grown or raised foods; and use of
      home-grown vegetables. DESIGN: Cross-sectional surveys. SETTING: Data from
      surveys conducted in Estonia, Latvia and Lithuania in the summer of 1997 were
      used to describe the three aspects of food security and their socio-economic
      correlates (using descriptive statistics and logistic regression). SUBJECTS:
      Representative samples of adults were selected in each country (Estonia, Latvia,
      Lithuania, ). RESULTS: Cost was the most commonly reported reason for choosing
      foods, particularly in Lithuania (67%) and Latvia (60%) (Estonia 41%), and
      especially among people with lower income levels. In each country, large
      proportions of respondents depended partially or entirely on home-grown or raised
      foods (Latvia 47%, Lithuania 42%, Estonia 32%) or used home-grown vegetables
      frequently (Lithuania 66%, Latvia 53%, Estonia 29%); this was particularly the
      case in rural areas. CONCLUSIONS: The issue of food security needs to be examined
      further in the Baltic Republics and other transitional economies as increased
      access to safe, healthy foods for all could help improve dietary intake and
      reduce the high mortality from non-communicable diseases. Access to affordable,
      high-quality fresh foods by different social groups should be monitored and the
      potential contribution of home-grown and raised foods to reduce food poverty
      should be explored further.

PMID- 12003651
TI  - Longitudinal study of energy and nutrient intakes for infants from low-income,
      urban families.
AB  - OBJECTIVE: To assess the energy and nutrient intakes of healthy infants from low
      income families and to compare intakes with current recommendations. DESIGN: We
      interviewed mother-infant pairs longitudinally when the infants were 3, 6, 9, 12,
      18 and 24 months old. Food intake data were obtained by 24-hour dietary recalls.
      Selected nutrient intakes were calculated and compared with the Recommended
      Dietary Allowances (RDAs). SUBJECTS/SETTING: Infants were the offspring of low
      income, pregnant women recruited at the Albany County Department of Health, New
      York for the Albany Pregnancy and Infancy Lead Study, a prospective investigation
      of factors related to blood lead levels, including nutrition. Interviews were
      conducted during paediatric clinic visits. STATISTICAL ANALYSES PERFORMED: Means
      and standard deviations were used to describe energy and micronutrient intakes
      for age groups. The probability approach was utilised to examine the prevalence
      of inadequate intakes. RESULTS: Mean energy and nutrient intakes generally met or
      exceeded the RDA. The exceptions were vitamin D and zinc for which observed means
      were below the RDA at several data points. Protein consumption was exceptionally
      high in this sample. The highest estimated prevalences of inadequate intakes were
      observed for iron, zinc and vitamin D at the older ages. CONCLUSIONS: This study
      identified several potential concerns about the diets of infants during the
      transition from infant food and formula to table foods. Low intakes of vitamin D,
      zinc and iron, especially at 12 and 18 months, were observed. High protein
      intakes were noted at all ages.

PMID- 12003652
TI  - A randomised trial in Mali of the effectiveness of weekly iron supplements given
      by teachers on the haemoglobin concentrations of schoolchildren.
AB  - OBJECTIVE: To assess the effect on the haemoglobin concentrations of
      schoolchildren of weekly iron tablets administered by teachers. DESIGN: Sixty
      schools were randomly assigned to two groups: in 30 schools children were given
      weekly for 10 weeks a tablet providing 65 mg of iron and 0.25 mg of folic acid;
      in the other 30 schools no iron tablets were given. All children were dewormed
      and given vitamin A before the study began. The haemoglobin concentration of up
      to 20 randomly selected children in each school was estimated before and 2 weeks
      after the end of treatment. SETTING: Rural community schools in Kolondieba
      district of Mali. SUBJECTS: Some 1113 schoolchildren aged 6-19 years with a mean
      of 11.4 years. RESULTS: The haemoglobin concentration of treated children rose on
      average by 1.8 g l(-1) and the prevalence of anaemia fell by 8.2%; in untreated
      children the haemoglobin concentration fell by an average of -2.7 g l(-1) and the
      prevalence of anaemia rose by 9.4%. The fall in haemoglobin concentration among
      untreated girls of -4.0 g l(-1) was greater than in untreated boys (-0.3 g l(-1)
      ). CONCLUSIONS: Weekly iron tablets given by teachers prevented a general fall in
      the haemoglobin concentrations of untreated children, and led to a small but
      statistically significant rise among treated children. Young children benefited
      more than children aged >or=12 years, and girls benefited more than boys.

PMID- 12003653
TI  - Tea consumption and the reduced risk of colon cancer -- results from a national
      prospective cohort study.
AB  - OBJECTIVE: This study examines the relationship between tea consumption and colon
      cancer risk in the US population. DESIGN: Data from the NHANES I Epidemiologic
      Follow-up study (NHEFS) were used to examine the hypothesis. Cox proportional
      hazard models were used to examine the hypothesis of a protective effect of
      frequent tea consumption on colon cancer occurrence. SETTING: Due to differences
      in the precision of the exposure data, we analysed two cohort periods based on
      the NHEFS. Cohort I was based on the survey conducted at the NHEFS baseline and
      Cohort II began at the first follow-up. SUBJECTS: After excluding non-incidence
      cases and cases lost to follow-ups, there were 2359 tea users and 6498 non-tea
      users at baseline and 7656 tea users and 4514 non-tea users at the first follow
      up. RESULTS: : After adjusting for confounders, the relative risks of colon
      cancer are 0.57 (95% confidence interval (CI) 0.42, 0.78) and 0.59 (95% 1.00) for
      subjects who consumed <or=1.5 cups and >1.5 cups per day, respectively, compared
      with non-tea users in Cohort II. Although more women consumed tea and the mean
      intake was higher, the preventive effect of tea consumption on colon cancer was
      found predominantly in men. The relative risks of colon cancer are 0.41 (95%
      0.66) for men who consumed <or=1.5 cups day-1 and 0.30 (95% 0.98) for >1.5 cups
      day-1 of tea consumption (P-value for trend <0.01). No significant results were
      found in Cohort I. CONCLUSIONS: This study suggests an inverse association
      between colon cancer risk and habitual tea consumption.

PMID- 12003654
TI  - Fish consumption and self-reported physical and mental health status.
AB  - OBJECTIVE: The aim of this study was to assess whether self-reported mental
      health status, measured using the SF-36 questionnaire, was associated with fish
      consumption, assessed using a food-frequency questionnaire. DESIGN: The cross
      national data were collected in the 1996/97 New Zealand Health Survey and 1997
      Nutrition Survey, which were conducted using the same sampling frame. Survey
      respondents were categorised into those who consumed no fish of any kind and
      those who consumed some kind of fish, at any frequency. Data were adjusted for
      age, household income, eating patterns, alcohol use and smoking. Other
      demographic variables and potential confounding nutrients were included in the
      preliminary analyses but were not found to have a significant relationship with
      fish consumption. SUBJECTS: Data from a nationally representative sample of 4644
      New Zealand adults aged 15 years and over were used in this analysis. RESULTS:
      Fish consumption was significantly associated with higher self-reported mental
      health status, even after adjustment for possible confounders. Differences
      between the mean scores for fish eaters and those who never eat fish were 8.2 for
      the Mental Health scale and 7.5 for the Mental Component score. Conversely, the
      association between fish consumption and physical functioning was in the opposite
      direction. CONCLUSIONS: This is the first cross-sectional survey to demonstrate a
      significant relationship between fish intake and higher self-reported mental
      health status, therefore offering indirect support for the hypothesis that omega
      3 polyunsaturated fatty acids may act as mood stabilisers.

PMID- 12003655
TI  - Longitudinal changes in nutrient intakes in the Melbourne Chinese Cohort Study.
AB  - OBJECTIVE: To assess longitudinal changes in the consumption of nutrients and the
      impact of socio-economic factors on diet transition in the Melbourne Chinese
      Health Study (MCHS) cohort. DESIGN: Longitudinal study including two phases:
      baseline (1989/90) and follow-up (1995/97). SETTINGS: Melbourne metropolitan
      areas in Victoria, Australia. STUDY SUBJECTS AND METHOD: Two hundred and sixty
      two Chinese men and women aged 25 years and over, recruited at baseline, who had
      completed the both baseline and follow-up food-frequency questionnaires. RESULTS:
      Women increased their daily intakes of energy (+549 kJ), protein (+7.8 g), fat
      (+7.3 g) and dietary fibre (+5.6 g) whereas men decreased their daily consumption
      of carbohydrate (-38.5 g) over an average period of 8 years. Energy contributions
      from protein and fat rose while that from carbohydrate dropped for all cohort
      subjects. Increased intakes of riboflavin, beta-carotene and iron were observed
      in men, while an increased consumption of thiamine, riboflavin, niacin and
      minerals (except sodium) was observed in women. Socio-economic factors such as
      education, family income levels and occupational categories appeared to have a
      far more powerful influence on changes in individual daily nutrient intakes than
      age or length of stay in Australia. Changes in nutrient intake in women were less
      affected by sociodemographic variables. CONCLUSION: The observed changes in
      nutrient intakes indicated a progressive approach towards the Australian
      Recommended Dietary Intakes within this Chinese cohort population.

PMID- 12003656
TI  - Foods prepared outside the home: association with selected nutrients and body
      mass index in adult Australians.
AB  - OBJECTIVE: To determine the proportion of energy from foods prepared outside the
      home (FPOH) and the relationships with energy and nutrient intakes and body mass
      index (BMI). DESIGN: A nutrition survey of a representative sample of the
      Australian population aged 18 years and over Measure used was a 24-hour dietary
      recall. Underreporters (energy intake/estimated basal metabolic rate (EI/BMR)
      <0.9) were excluded from analysis. Daily energy and selected nutrient intakes
      were calculated using a 1996 nutrient composition database for all
      foods/beverages during the 24-hour period. RESULTS: On average FPOH contributed a
      significant 13% to total energy intake. About a third of the sample had consumed
      FPOH in the last 24 hours and on average this group consumed a third of their
      total energy as FPOH. The relative contributions of fat (for men and women) and
      alcohol (for women) were significantly higher for those in the top tertile of
      FPOH consumers. The intakes of fibre and selected micronutrients (calcium, iron,
      zinc, folate and vitamin C) were significantly lower in this group. After
      adjustment for age and income no relationship between FPOH and BMI was observed.
      CONCLUSIONS: FPOH make a significant contribution to the energy intake of a third
      of the Australian population. FPOH contribute to poor nutritional intakes.
      Altering the supply of FPOH may be an effective means of improving diets at a
      population level.

PMID- 12003657
TI  - Dietary intake of 9-10-year-old and 11-12-year-old children in Liverpool.
AB  - OBJECTIVE: To describe the eating habits of children in Liverpool and compare two
      age groups that bridge the transition from primary to secondary school. DESIGN:
      Two cross-sectional studies carried out one year apart using a food intake
      questionnaire that records whether or not each child claims to have eaten
      specific marker foods on the previous day. SETTING: Primary and secondary schools
      in Liverpool. SUBJECTS: Six hundred and forty-nine children aged 11 or 12 years
      and 3556 children aged 9 or 10 years. RESULTS: Fewer older children ate breakfast
      (68-82%), especially the girls, and not eating breakfast was associated with
      eating on the way to school in the younger children. More of the older girls ate
      nothing at breakfast or on the way to school. Overall, the less desirable foods
      were reported to have been eaten by more children, of both ages, than the more
      desirable foods. Fruit, however, was mentioned by most children (69-77%) but the
      next 10 foods mentioned by most children were all less desirable ones. Only 31%
      of primary and 21% of secondary children ate both fruit and vegetables but 23% of
      primary and 26% of secondary children ate neither fruit nor vegetables. Overall,
      more of the girls of both age groups claimed to have eaten foods that would
      normally be encouraged. CONCLUSIONS: Food choice changes appreciably between
      primary and secondary school and, in some key respects, for the worse. In
      particular, far more children of both age groups need to be eating fruit and
      vegetables every day.

PMID- 12003658
TI  - Dieting patterns and related lifestyles of school-aged children in the Republic
      of Ireland.
AB  - OBJECTIVE: The aim of this study was to identify differences in food habits and
      lifestyle behaviours by dieting status among young people in Ireland. DESIGN:
      Cross-sectional survey. Participants responded to a self-completion questionnaire
      designed by researchers on the World Health Organization's collaborative study -
      Health Behaviour in School Aged Children. Pupils were selected by school and
      classroom and the sample was stratified to be representative of the geographical
      distribution of school students in Ireland. SETTING: Data were collected by
      teachers from school pupils in their classrooms. SUBJECTS: Data were collected
      from 187 schools which included 8497 pupils (51% girls) aged 9-17 years. RESULTS:
      While a minority of pupils (12% of girls, 4% of boys) reported that they were on
      a diet to lose weight, a substantial proportion (28% of girls, 18% of boys) said
      that they should be on a diet. Dieters reported consuming unhealthy foods less
      frequently than non-dieters, but did not report an increased consumption of fruit
      and vegetables. Rather, some categories of dieters reported higher levels of
      coffee and tobacco use and lower exercise levels than non-dieters. CONCLUSIONS:
      The results could indicate substitution of unhealthy foods by other unhealthy
      behaviours as opposed to an increased consumption of healthier foodstuffs, and
      suggest that both smoking and exercise need to be addressed alongside nutrition
      in youth health promotion.

PMID- 12003659
TI  - Use of dietary supplements in Denmark is associated with health and former
      smoking.
AB  - OBJECTIVES: To describe the use of dietary supplements in a group of Danish
      adults and to investigate the differences between users and non-users with
      respect to age, gender, health and lifestyle factors. DESIGN: Cross-sectional
      study in two Danish cities. SETTING: The Danish Investigation on Iodine Intake
      and Thyroid Diseases, 1997-1998. SUBJECTS: Participants were 3707 women (selected
      age groups between 18 and 65 years) and 942 men (60-65 years). Participation rate
      was 50%. Supplement data were collected in a personal interview. Data on
      education, smoking, alcohol intake, physical activity, use of medication and self
      perceived health were derived from a self-administered questionnaire. Multiple
      logistic regression was used for the statistical analysis. RESULTS: Participants
      were asked about all kinds of supplements, ranging from products containing
      vitamins and minerals, to fish oils and products of herbal origin. On average 59%
      reported use of some kind of dietary supplement. Most common were combined
      multivitamin/mineral products (48%) followed by single vitamin C products (10%).
      Twelve per cent used three or more different supplements. Supplement use was
      strongly associated with age and gender, being highest among elderly women (78%).
      Ex-smokers were more likely to use supplements than subjects who had never smoked
      (odds ratio (OR) 1.36, 95% confidence interval (CI) 1.09-1.76). Supplement use
      was more likely among subjects who had many days of illness 95% CI 1.12-1.66) and
      among users of medication 95% CI 1.04-1.42). Subjects who perceived their health
      as poor were more likely to use supplements other than just a
      multivitamin/mineral tablet 95% CI 1.31-3.77). CONCLUSIONS: Use of dietary
      supplements was related to age, gender and smoking, but also to poor self
      perceived health status and absence from work. This indicates that a group of
      people use supplements as a form of self-medication.

PMID- 12003660
TI  - Stakeholder interactions and the development of functional foods.
AB  - OBJECTIVE: This paper investigates the roles of the individual stakeholders
      involved in the development of functional foods and the implications of their
      actions for public perception of this new food concept. RESULTS: At a time when
      consumer awareness of the link between diet and health is strong, a new food
      concept incorporating of a wide spectrum of foods has captured the imagination of
      the food industry and consumers alike. Functional foods provide a new category of
      foods that appear to be offering the public the opportunity to achieve a healthy
      lifestyle with minimal effort. Public perception may determine whether this new
      food concept is to become the next successful breakthrough in nutritional science
      or just another marketing gimmick devised by food manufacturers. The paper also
      addresses issues that arise directly as a result of the emergence of functional
      foods, such as appropriate legislation in connection to health claims in order to
      ensure consumer protection and also the lack of clarity in relation to
      definitions of what constitutes a functional food. CONCLUSION: The paper
      concludes that functional foods can only reach their maximum potential if the
      food industry, government and health professionals work together to improve
      communication between themselves and consumers and also to educate consumers,
      thereby allowing them to make informed decisions about dietary choices.

PMID- 12003661
TI  - Motivations for fruit and vegetable consumption in the UK Women's Cohort Study.
AB  - BACKGROUND: Despite recommendations to increase fruit and vegetable consumption
      within the UK population, intakes are still too low. In order to stimulate
      dietary behaviour change the determinants of food choice need to be explored.
      OBJECTIVES: To investigate how the priorities of high consumers of fruit and
      vegetables differ from those of low consumers, with respect to food choice
      motivations, and to identify what value high and low consumers place on different
      aspects of food choice behaviour. DESIGN: A 4-day food diary and a questionnaire,
      including The Food Choice Questionnaire (FCQ) and a measure of Stage of Change
      (SOC) for fruit and vegetable consumption, were administered to subjects.
      Motivation scores from the FCQ were compared with fruit and vegetable intake and
      SOC data. SUBJECTS: Nine hundred and ninety-eight females, aged 35-69 years,
      participating in the UK Women's Cohort Study. RESULTS: In a multiple linear
      regression model, including age, education level and all FCQ motivations, the
      strongest motivations specifically affecting fruit and vegetable intake were
      health and natural content. It was found that, for a one point increase (measured
      on a scale of 0-4) in health and natural content scores, fruit and vegetable
      consumption increased by 1.11 portions (95% confidence interval (CI) 0.5-1.7) and
      0.84 portions (95% CI 0.4-1.3), respectively The SOC evaluation showed
      significant associations with portions of fruit and vegetables consumed Women
      whose SOC was classed as maintenance phase were found to score higher on health,
      natural content, weight control and ethical concern factors These women also
      scored lower on convenience questions CONCLUSION: In this particular group of
      women the most important motivating factors for food choice, within the high
      fruit and vegetable consumers, were health and natural content of the food.

PMID- 12003662
TI  - Validation and calibration of food-frequency questionnaire measurements in the
      Northern Sweden Health and Disease cohort.
AB  - OBJECTIVES: To evaluate the reproducibility of, and to compare and calibrate,
      diet measures by the Northern Sweden 84-item food-frequency questionnaire (FFQ)
      with measures from 24-hour diet recalls (24-HDR). DESIGN: Randomly selected
      respondents from the EPIC (diet-cancer) and MONICA (diet-cardiovascular disease)
      study cohort in Northern Sweden were invited to answer the FFQ twice over a one
      year interval (FFQ1 and FFQ2), and to complete ten 24-hour recalls (reference
      method) in the months between. Plasma beta-carotene concentrations were
      determined from a subset of 47 participants. SETTING: Vasterbotten and
      Norrbotten, Northern Sweden. PARTICIPANTS: Ninety-six men and 99 women, who
      completed the study. RESULTS: The reproducibility of the FFQ was high in terms of
      both mean energy and nutrient intakes and relative ranking of participants by
      intake levels (median Pearson correlation of 0.68). Moderately higher food intake
      frequencies were recorded by FFQ1 compared with 24-hour recalls for dairy
      products, bread/cereals, vegetables, fruits and potato/rice/pasta, whereas meat,
      fish, sweet snacks and alcoholic beverage intakes were lower. The median Spearman
      coefficient of correlation between FFQ1 and the average of ten 24-HDR
      measurements was 0.50. Daily energy and nutrient intakes were similar for FFQ1
      and 24-HDR measurements, except for fibre, vitamin C, beta-carotene and retinol
      (FFQ1>24-HDR) and sucrose and cholesterol Pearson coefficients of correlation
      between FFQ1 and 24-HDR corrected for attenuation due to residual day-to-day
      variation in the 24-HDR measurements ranged from 0.36 to 0.79 (median 0.54).
      Adjustment for energy had only very moderate effects on the correlation
      estimates. Calibration coefficients estimated by linear regression of the 24-HDR
      on the FFQ1 measurements varied between 0.30 and 0.59 for all nutrients except
      alcohol, which had calibration coefficients close to 1.0. These low calibration
      coefficients indicate that relative risk estimates corresponding to an absolute
      difference in dietary intake levels measured by the FFQ will generally be biased
      towards 1.0. Plasma beta-carotene levels had a Pearson coefficient of correlation
      of 0.47 with the 24-HDR measurements, and of 0.23 with FFQ1 measurements.
      CONCLUSIONS: The Northern Sweden FFQ measurements have good reproducibility and
      an estimated level of validity similar to that of FFQ measurements in other
      prospective cohort studies. The results from this study will form the basis for
      the correction of attenuation and regression dilution biases in relative risk
      estimates, in future studies relating FFQ measurements to disease outcomes.

PMID- 12003663
TI  - A questionnaire assessment of nutrition knowledge--validity and reliability
      issues.
AB  - OBJECTIVE: This study describes an evaluation of validity and reliability
      measures in a questionnaire designed to assess knowledge of applied nutrition in
      children participating in an after-school care dietary intervention programme
      being undertaken in an area of high social disadvantage. DESIGN: Three domains
      were assessed: Knowledge of Applied Nutrition (KN), Knowledge of Food Preparation
      (KP) and Perceived Confidence in Cooking Skills (PC). Four pilot studies were
      undertaken to determine item reliability, test-retest reliability, discrimination
      and difficulty indices, and content, cognitive and face validity. SETTING:
      Primary schools in Dundee, Scotland and Newcastle upon Tyne, England. SUBJECTS:
      Ninety-eight children aged 11 years. RESULTS: The final instrument comprised 36
      questions (18 KN items, 9 KP items and 9 PC items) presented on four sides of
      paper, which could be self-completed in less than 15 minutes. Question formatting
      included open and closed structures (KP) and multiple choice (KN and PC) items.
      All knowledge questions could be answered correctly by 5 to 95% of the target
      population, with discrimination scores ranging from 0.06 to 0.83. Retest
      reliability scores were significant (KN 0.458, KP 0.577, PC 0.381, ) and internal
      reliability (Cronbach's alpha) of each component was also significant.
      CONCLUSION: The test meets basic psychometric criteria for reliability and
      validity and forms a suitable instrument for measuring changes associated with
      intervention work aimed at improving food and dietary knowledge.

PMID- 12003664
TI  - Reference values for serum levels of vitamin B12 and folic acid in a population
      based sample of adults between 35 and 80 years of age.
AB  - OBJECTIVES: To examine folic acid and vitamin B12 status in a group of 1000
      persons sampled from the community of Umea, Sweden, and aged 35, 40, 45, 50, 55,
      60, 65, 70, 75 or 80 years. Reference data for folate and age-stratified
      reference data for vitamin B12 are presented, together with an examination of
      potential confounders. MEASUREMENTS: All subjects participated in extensive
      health examinations and interviews, and laboratory blood testing was performed.
      RESULTS: A series of exclusion criteria were applied, and data from 961 subjects
      were analysed. Vitamin B12 levels were found to decrease with increasing age,
      whereas folate levels remained constant across the age span studied. None of the
      vitamins was found to vary with sex, education, smoking or alcohol consumption,
      body mass index, prescription-free vitamin supplements, level of haemoglobin, or
      mean cell volume of erythrocytes. Further, none of these factors was associated
      with the age-related decrease of vitamin B12 level. CONCLUSIONS: The offered
      reference ranges should be used only in order to rule out deficiency. For B12
      levels, the age of the subject should be considered such that, for elderly people
      in particular, values above the medians should be considered as indicative of
      normal vitamin status.

PMID- 12003665
TI  - Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth.
AB  - Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that influences cellular
      phenotype and the structure of the extracellular matrix. These effects are
      important components of the tissue remodeling that is associated with
      angiogenesis and neoplasia. The genetic mutations in oncogenes and tumor
      suppressor genes that occur within tumor cells are frequently associated with
      decreased expression of TSP-1. However, the TSP-1 that is produced by stromal
      fibroblasts, endothelial cells and immune cells suppresses tumor progression. TSP
      1 inhibits angiogenesis through direct effects on endothelial cell migration and
      survival and through indirect effects on growth factor mobilization. TSP-1 that
      is present in the tumor microenvironment also acts to suppress tumor cell growth
      through activation of transforming growth factor beta in those tumor cells that
      are responsive to TGF beta. In this review, the molecular basis for the role of
      TSP-1 in the inhibition of tumor growth and angiogenesis is summarized.

PMID- 12003666
TI  - Potentiation of angiogenic response by ischemic and hypoxic preconditioning of
      the heart.
AB  - This review is intended to discuss the newly discovered role of preconditioning
      which should make it an attractive therapeutic stimulus for repairing the injured
      myocardium. We recently found that apart from rendering the myocardium tolerant
      to ischemic reperfusion injury, preconditioning also potentiates angiogenesis.
      Our study demonstrated for the first time that both ischemic and hypoxic
      preconditioning triggered myocardial angiogenesis at the capillary and arteriolar
      levels which nicely corroborated with the improved myocardial contractile
      function. Hypoxic preconditioning resulted in the stimulation of VEGF, the most
      potent angiogenic factor known to date. In concert, endothelial cell specific
      tyrosine kinase receptors, Tie 1, Tie 2 and Flt-1 and Flk-1 were also
      significantly enhanced in the preconditioned myocardium. The redox-regulated
      transcription factor NF kappa B was found to play an essential role in the
      preconditioning regulation of angiogenesis.

PMID- 12003667
TI  - Regulation of apoptosis by the ubiquitin and proteasome pathway.
AB  - Regulated proteolysis plays important roles in cell physiology as well as in
      pathological conditions. In most of the cases, regulated proteolysis is carried
      out by the ubiquitin- and proteasome-dependent proteolytic system, which is also
      in charge of the bulk of cytoplasmic proteolysis. However, apoptosis or the
      process of programmed cell death is regulated by a different proteolytic system,
      i.e. by caspases, a family of specialized cysteine proteases. Nevertheless, there
      is plenty of evidence of a crosstalk between the apoptotic pathways and the
      ubiquitin and proteasome system, whose function in apoptosis appears to be very
      complex. Proteasome inhibitors induce apoptosis in multiple cell types, while in
      other they are relatively harmless or even prevent apoptosis induced by other
      stimuli. Proteasomes degrade specific proteins during apoptosis, but on the other
      hand some components of the proteasome system are degraded by caspases. The
      knowledge about the involvement of the ubiquitin- and proteasome-dependent system
      in apoptosis is already clinically exploited, since proteasome inhibitors are
      being tested as experimental drugs in the treatment of cancer and other
      pathological conditions, where manipulation of apoptosis is desirable.

PMID- 12003668
TI  - Myocardial changes after spironolactone in spontaneous hypertensive rats. A laser
      scanning confocal microscopy study.
AB  - The present study aims to objectivate by laser scanning confocal microscopy, the
      cardiac structure of the spontaneously hypertensive rats (SHR) treated with
      different doses of spironolactone, either alone or in combination with an
      angiotensin converting enzyme inhibitor or with a calcium channel blocker. Thirty
      SHRs were divided into six groups and treated during 13 weeks as follows:
      control, spironolactone (5, 10 and 30 mg/kg/day), spironolactone + enalapril and
      spironolactone + verapamil. Spironolactone action on the SHR blood pressure (BP)
      was dose-dependent. The cardiac hypertrophy was affected by the treatment with
      spironolactone (high dose) or a combination of spironolactone and Enalapril. The
      myocardial structure was less affected by the spironolactone monotherapy (at all
      doses) showing hypertrophied cardiac myocytes, focal areas of the reactive
      fibrosis, inflammatory infiltrate. The treatment with spironolactone in
      combination with enalapril or verapamil prevented these alterations. In
      conclusion, the monotherapy with spironolactone had only a limited effect in the
      preservation of the myocardial structure and in the attenuation of the
      interstitial fibrosis in SHRs, even after high dose. This action on the
      myocardium is more efficient when the spironolactone (even in medium dose) was
      associated with enalapril or verapamil.

PMID- 12003669
TI  - Neoductular progenitor cells regenerate hepatocytes in severely damaged liver: a
      comparative ultrastructural study.
AB  - In severely injured liver, stem cells give rise to progeny that tend to replace
      lost hepatocytes. Neoductular reaction appears as an inherent stage of liver
      reconstruction following severe damage caused by different pathological
      mechanisms. Few ultrastructural types of progenitor cells have been described,
      and some molecular phenotypes of progenitor stages have been characterized, but
      the details of the differentiation process are largely unknown. We prepared for
      light and electron microscopy examination human liver from biopsies of patients
      with chronic active hepatitis, and rat liver with allyl alcohol-induced
      periportal necrosis. We found that progenitor neoductular cells acquire the
      hepatocytic polarity pattern during a multi-step process apparently involving
      cell migration and dissolution of neoductular basement membrane. An intermediate
      stage with "mixed" ductular and hepatocytic polarity was described.

PMID- 12003670
TI  - The study of CTLA-4 and vitamin D receptor polymorphisms in the Romanian type 1
      diabetes population.
AB  - Several studies suggested that part of the genetic susceptibility for Type 1
      diabetes (T1DM) is encoded by some polymorphisms of CTLA-4 gene (2q33) and of
      Vitamin D Receptor gene (VDR; 12q12-14). Our aim was to assess their contribution
      to T1DM genetic susceptibility in the Romanian population. We typed CTLA-4 49 A/G
      and VDR FokI (F/f), ApaI (A/a) and TaqI (T/t) polymorphisms by Sequence Specific
      Primer PCR (SSP-PCR) in 204 Romanian diabetic families (756 individuals: 212 T1DM
      probands and 544 unaffected parents and siblings). We studied alleles
      transmission using the Transmission Disequilibrium Test (TDT). We found an
      increased transmission of CTLA-4 49G allele to diabetics (54.8%, p=0.11). The
      transmission of F (56.1%, p=0.063), a (55.7%, p=0.061) and T (51.8%, p=0.37)
      alleles of VDR gene to diabetics was increased but did not reach statistical
      significance. In conclusion we found the same increased transmission of CTLA-4 49
      G allele to diabetics as previously reported. VDR FoqI F allele seems to be
      predisposing while TaqI T allele seems to be protective.

PMID- 12003671
TI  - Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells.
AB  - We investigated the time-dependence of apoptotic events in EL4 cells by
      monitoring plasma membrane changes in correlation to DNA fragmentation and cell
      shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X
      rays) and we looked at various markers to follow the early-to-late apoptotic
      events: phospholipid translocation (identified through annexin V-fluorescein
      assay and propidium iodide), lipid package (via merocyanine assay), membrane
      fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the
      fluorescence-labeling test and cell size measurements. The different apoptotic
      inducers caused different reactions of the cells: staurosporine induced apoptosis
      most rapidly in a high number of cells, tubercidine triggered apoptosis only in
      the S phase cells, while X-rays caused a G2/M arrest and subsequently apoptosis.
      Loss of lipid asymmetry is promptly detectable after one hour of incubation time.
      The phosphatidylserine translocation, decrease of lipid package and anisotropy,
      and the increase of membrane fluidity appeared to be based on the same process of
      lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage
      appear to be parallel and independent processes running on different time scales
      but which are kinetically inter-related. The results indicate different signal
      steps to apoptosis dependent on inducer characteristics but the kinetics of
      "early-to-late" apoptosis appears to be a fixed program.

PMID- 12003672
TI  - Image processing, diagnostic information extraction and quantitative assessment
      in pathology.
AB  - As we enter the information age we hold strong beliefs in the benefits of digital
      technology applied to pathology: numerical representation offers objectivity.
      Digital knowledge may indeed lead to significant information discovery, and,
      processing systems might be designed to allow a true evolution of capabilities.
      Questions arise whether the methodology underlying quantitative analysis provides
      the information that we need and whether it is appropriate for some of the
      problems encountered in diagnostic and prognostic histopathology. While one
      certainly would not dispute the value of statistical procedures, the clinical
      needs call for individual patient targeted prognosis.

PMID- 12003673
TI  - Structural determinants of atrial and ventricular conduction.

PMID- 12003674
TI  - Modified lipoproteins accumulate in human coronary atheroma.

PMID- 12003675
TI  - Molecular, immunological and clinical properties of mutated hepatitis B viruses.
AB  - Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic
      active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some
      groups of patients with high risk of generation of HBV mutants: infected infants,
      immunosuppressed individuals (including hemodialysis patients), patients treated
      with interferon and lamivudine for chronic HBV infection. These groups are the
      target for molecular investigations reviewed in this paper. The emergence of
      lamivudine- or other antiviral-resistant variants, rises concern regarding long
      term use of these drugs. Infection or immunization with one HBV subtype confers
      immunity to all subtypes. However, reinfection or reactivation of latent HBV
      infection with HBV mutants have been reported in patients undergoing transplant
      and those infected with HIV. Mutations of the viral genome which are not
      replicative incompetent can be selected in further course of infection or under
      prolonged antiviral treatment and might maintain the liver disease. Four open
      reading frames (ORF) which are called S-gene, C-gene, X-gene and P-gene were
      identified within the HBV genome. Mutations may affect each of the ORFs. Mutated
      S-genes were described to be responsible for HBV-infections in successfully
      vaccinated persons, mutated C-genes were found to provoke severe chronic liver
      diseases, mutated X-genes could cause serious medical problems in blood donors by
      escaping the conventional test systems and mutated P-genes were considered to be
      the reason for chemotherapeutic drug resistance. This paper reviews molecular,
      immunological and clinical aspects of the HBV mutants.

PMID- 12003677
TI  - The stress-vulnerability hypothesis in psychotic disorders: focus on the stress
      response systems.
AB  - The vulnerabilty stress model is an intriguing concept to look into the etiology
      of psychotic disorders and, in particular, into the "nature nurture" principle.
      That stress affects a vulnerable nature may be obvious, but its mechanism is not
      well understood, and many questions remain to be answered, let alone how to
      define "vulnerability". The present review tries to focus on the core issues of
      the vulnerability stress concept--identifying vulnerability, the way stress
      interferes with it, and the possiblilities of modulating their interaction.
      Attention is drawn to the biologic stress response systems, the autonomic nervous
      system (ANS), the hypothalamic pituitary adrenal (HPA) system, and the immune
      system, and highlights the plasticity of the HPA system as the mediator of
      adaptation.

PMID- 12003678
TI  - Corticosteroids, immune suppression, and psychosis.
AB  - The role of the immune system in psychiatric symptoms has been an area of much
      interest for many years. This review discusses medications and medical illnesses
      associated with immune system dysfunction, and their relationship to psychiatric
      symptoms, particularly psychosis. Medical illnesses including HIV infection,
      systemic lupus erythematosus (SLE), and Cushing's disease are all associated with
      psychiatric symptoms. In addition, high dosages of prescription corticosteroids
      (eg, prednisone and dexamethasone) are associated with mood changes, cognitive
      deficits, and even psychosis. However, the role of the immune system in mediating
      the psychiatric disturbances with each of these conditions is not clear.
      Directions for further research and treatment considerations are discussed.

PMID- 12003679
TI  - Stimulant-induced psychosis and schizophrenia: the role of sensitization.
AB  - Three different conditions, psychostimulant-induced behavioral sensitization in
      rodents, psychostimulant-induced psychoses in human, and chronic schizophrenia
      show similar longitudinal alternations, progressively enhanced susceptibility to
      abnormal behaviors, psychotic state, and relapse. Sensitization phenomena to the
      drugs or endogenous dopamine should be involved in the mechanisms underlying the
      development of such susceptibility. Recently, an enhanced dopamine release in
      vivo by amphetamine administration in the striatum has been shown in
      schizophrenics, which is a replication of that previously proven in the
      behavioral sensitization in rats. Accordingly, common molecular mechanisms of
      sensitization phenomena must develop in these three conditions, and are
      overviewed in this review

PMID- 12003680
TI  - Postpartum psychoses: prognosis, risk factors, and treatment.
AB  - Puerperal psychoses do not represent a nosological entity, but rather a selection
      of puerperally triggered "ordinary" functional psychoses with cycloid psychoses
      predominating and schizophrenias occurring very rarely. The prognosis is
      basically favorable concerning symptom remission and social and occupational
      functioning. However, there is a considerable frequency of relapses and an
      increased suicide rate. The most important risk factors for an episode of a
      puerperal psychosis are being primiparous and having suffered a previous episode
      of a psychosis, particularly a cycloid psychosis. Controlled treatment studies up
      to now are absent. Case studies suggest in acute episodes the efficacy of a
      symptom-oriented pharmacologic treatment where ablactation is recommended. With
      respect to prophylactic treatment some authors propose to apply lithium in late
      pregnancy or immediately after delivery. Because of its possible teratogenic
      effects and the altogether rather sparse data, the authors however cannot
      recommend the use of lithium during pregnancy. Applying estradiol after delivery
      may be beneficial and safe, but further studies are necessary to clarify these
      issues.

PMID- 12003681
TI  - Cannabis and psychosis.
AB  - There has been considerable debate about the reasons for the association observed
      between cannabis use and psychosis in both clinical and general population
      samples. Among the hypotheses proposed to explain the association are the
      following: 1) common factors explain the co-occurrence; 2 cannabis causes
      psychosis that would not have occurred in the absence of cannabis use; 3)
      cannabis precipitates psychosis among persons who were vulnerable to developing
      the disorders; 4) cannabis use worsens or prolongs psychosis among those who have
      already developed the disorder; and 5) that persons with psychosis are more
      likely to become regular or problematic cannabis users than persons without
      psychosis. This article evaluates the evidence on each of these hypotheses,
      including recent research on the role of the cannabinoid receptor system in
      schizophrenia. The evidence suggests that common factors do not explain the
      comorbidity between cannabis use and psychosis, and it is unlikely that cannabis
      use causes psychosis among persons who would otherwise not have developed the
      disorder. The evidence is more consistent with the hypotheses that cannabis use
      may precipitate psychosis among vulnerable individuals, increase the risk of
      relapse among those who have already developed the disorder, and may be more
      likely to lead to dependence in persons with schizophrenia.

PMID- 12003684
TI  - The role of antipsychotics in treating delirium.
AB  - The mainstay of the pharmacologic management of delirium remains typical
      antipsychotics, primarily haloperidol. Typical antipsychotics are associated with
      significant side effects, particularly in the elderly. This article reviews the
      literature on the use of both typical and atypical antipsychotics in the
      management of acute delirium, with a focus on the elderly. In this population,
      typical antipsychotics are associated with substantially more drug induce side
      effects--either extrapyramidal side effects or anticholinergic effects from the
      antipsychotics alone or in combination with benztropine or trihexyphenidyl.
      Anticholinergic toxicity is especially problematic in delirious, demented
      patients, because most dementias are associated with pre-existing deficiencies in
      cholinergic neurotransmission. These issues will be reviewed for typical
      antipsychotics as well as the emerging literature on the use of atypical
      antipsychotics-- risperidone, olanzapine, and quetiapine--for pharmacologic
      management of acute delirium. Data from two studies conducted at the Wesley Woods
      Center at Emory University will be briefly reviewed as they constitute the
      largest series to date investigating the pharmacologic management of delirious
      demented patients.

PMID- 12003683
TI  - Delirium: an important (but often unrecognized) clinical syndrome.
AB  - Delirium is a clinical syndrome characterized by the acute onset of a disturbance
      in consciousness accompanied by a reduced ability to focus, sustain, or shift
      attention. It may foreshadow impending death in as many as 25% of hospitalized
      inpatients and may be a source of significant morbidity in those who present with
      this syndrome. The disorder may go unrecognized by hospital staff as well as
      those close to an affected individual, and this oversight may lead to poorer
      outcomes including longer lengths of stay in acute care hospitals, the need for
      nursing home placement, prolonged cognitive disturbances, and protracted
      disability. This paper will address this complex condition, focusing on its
      history, definition, epidemiology, pathophysiology, recognition, risk factors,
      and clinical quantification. Its prevention and treatment will be covered
      elsewhere in this journal.

PMID- 12003685
TI  - Mood disorders and chronic obstructive pulmonary disease: current research and
      future needs.
AB  - The following review examines the interrelationships between chronic obstructive
      pulmonary disease (COPD), psychiatric illness, and tobacco use. The influence
      that these three entities have is very unclear, and this article attempts to
      address the current knowledge of how each contributes to the other and postulates
      future directions to explore regarding diagnosis, treatment, and predictive
      values. Other issues discussed include the pharmacologic treatment of patients
      with COPD and depression, and an overview of the clinical trial data regarding
      several different classes of antidepressants. Also reviewed is the impact of
      pulmonary rehabilitation on psychologic status and quality of life issues in the
      daily functioning of the COPD patient.

PMID- 12003687
TI  - Neuropsychiatric aspects of human immunodeficiency virus (HIV) infection.
AB  - Human immunodeficiency virus (HIV) infection with central nervous system (CNS)
      involvement causes a variety of psychiatric complications among a significant
      proportion of infected individuals. A cure for the fully developed AIDS related
      to HIV infection remains elusive, and HIV/AIDS is a leading cause of death among
      adults between the ages of 25 and 44. Life expectancy, however, has gradually
      increased over the years, resulting in a concern for a potential increase in the
      incidence of secondary psychiatric manifestations. Knowledge of the
      neuropathology of HIV-CNS dysfunction and familiarity with its clinical
      presentation can aid clinicians in a determination of the appropriate therapy
      inclusive of psychiatric care that may be useful for a specific individual in
      their treatment.

PMID- 12003686
TI  - Pharmacologic treatment of mood disorders in acquired immune deficiency syndrome
      (AIDS).
AB  - Mood disorders in HIV are common and can impact on the course of the illness.
      With the increasing use of newer psychopharmacologic and antiviral medications,
      clinicians need to take precautions while prescribing them. This paper gives an
      overview of the most recent literature describing the pharmacologic treatment of
      mood disorders in HIVpositive patients. The authors of this paper focus on
      antidepressants, mood stabilizers, neuroleptics, and psychostimulants, as well as
      on areas of controversy. The authors' own clinical experiences are also included.

PMID- 12003688
TI  - Substance abuse issues in cancer pain.
AB  - It is estimated that 40% to 50% of patients with metastatic disease and 90% of
      patients with terminal cancer experience unrelieved pain. Furthermore, inadequate
      treatment of cancer pain is a greater possibility if the patient is a substance
      abuser. In this paper, we will explore pertinent conceptual and clinical aspects
      of addiction that can assist in improving the identification and treatment of
      patients with substance use disorders.

PMID- 12003689
TI  - The role of a pharmacist in ambulatory cancer pain management.
AB  - Cancer pain is progressive and complex. The multidimensional character of cancer
      pain requires comprehensive management by a multidisciplinary team of health care
      professionals. Pharmacotherapy is a cornerstone of cancer pain management.
      Pharmacists who are engaged in ambulatory cancer pain management can play a
      pivotal role in the pharmacotherapy of cancer pain by optimizing medication
      therapy, monitoring outcomes, enhancing adherence through patient education
      regarding drug use, pain and symptom control, educating other health
      professionals and students, and conducting research. To fully meet the
      therapeutic challenges of cancer pain, pharmacists need to improve their
      knowledge and attitudes about cancer pain and pain medications.

PMID- 12003690
TI  - Sedation for comfort at end of life.
AB  - Treatment for patients who are dying from cancer and are suffering with
      physiologic and existential symptoms is an important and valuable skill for
      health care providers. However, the treatment for suffering at the end of life
      and the use of sedation for comfort often are misunderstood. The following is a
      discussion of the clinical skills and ethical considerations that health care
      providers should have when treating terminal patients with cancer.

PMID- 12003691
TI  - Interventional approach to cancer pain.
AB  - Cancer pain is a significant problem despite the advent of the World Health
      Organization's cancer pain guidelines, the US government's cancer pain
      guidelines, and the Joint Commission's mandate for hospital pain evaluation and
      treatment. Ninety percent of patients with cancer pain can be effectively treated
      with oral conservative medications. The remaining 10% need more invasive
      treatments to control their pain. This article reviews current methods of
      controlling cancer pain using intrathecal catheters, nerve blocks, and
      neurosurgical procedures.

PMID- 12003692
TI  - Headaches in cervical artery dissections.
AB  - Internal carotid artery (ICA) and vertebral artery (VA) dissections are among the
      common causes of stroke in middle-aged and young adults. The spectrum of clinical
      presentations of these dissections is broad. Many patients, especially those with
      ICA dissections, may never develop a stroke.

PMID- 12003693
TI  - Idiopathic intracranial hypertension headache.
AB  - Idiopathic intracranial hypertension (IIH) is a disorder of increased
      intracranial pressure that may have papilledema with normal imaging study
      results. Headache is the most frequent symptom. Although the headache
      characteristics are indistinguishable from the symptoms of migraine headache,
      accompanying symptoms of increased intracranial pressure, such as pulsatile
      tinnitus, transient visual obscurations, and radicular neck pain, may aid in the
      diagnosis. Magnetic resonance imaging, including venography, is essential for the
      diagnosis of the primary idiopathic intracranial hypertension. Medical treatment
      for the headache includes weight loss for obese patients, diuretic therapy, and
      migraine preventive medications. If medical therapy does not abolish the
      headache, surgical options should be considered. Because patients with IIH have a
      poor quality of life, patient education and supportive materials are important.

PMID- 12003695
TI  - Complicated migraine and migraine variants.
AB  - This article reviews the less frequently encountered varieties of migraine. It is
      suggested that these disorders be approached by evaluating possible underlying
      etiologies before positively diagnosing migraine. This decreases the likelihood
      of "missing" structural or metabolic disorders. The classification, diagnostic
      evaluation, differential diagnosis, and treatment options of these disorders is
      reviewed and a selection of references appended for additional information.

PMID- 12003694
TI  - Thunderclap headache.
AB  - Thunderclap headache refers to an excruciating headache of instantaneous onset.
      It occurs as suddenly and unexpectedly as a "clap of thunder." Patients with
      thunderclap headache may have normal neurologic examination results and normal
      computed tomographic brain scans, even if they have serious underlying pathology.
      This has created confusion regarding nosology and the nature and extent of the
      diagnostic evaluation, which this article discusses.

PMID- 12003696
TI  - Drug overuse and rebound headache.
AB  - The overuse of acute medications in patients who are headache-prone poses a great
      challenge to headache management. Medication overuse-induced headache represents
      one of the most common iatrogenic disorders. It is the reason that most patients
      visit headache subspecialty clinics worldwide and often is the cause of an
      intractable or worsening headache in primary headache sufferers. The recent
      development of acute headache medications, especially the triptans, has provided
      increased migraine relief; however, the incidence of triptan-overuse headache has
      also increased. Awareness of medication overuse-induced headache and familiarity
      with the diagnosis and the treatment of this disorder are important to physicians
      who treat patients with headache.

PMID- 12003697
TI  - Ambulatory and self-monitoring of blood pressure: coming of age.

PMID- 12003698
TI  - Effect of ramipril versus amlodipine on renal outcomes in hypertensive
      nephrosclerosis.

PMID- 12003699
TI  - Angiotensin converting enzyme inhibitors or angiotensin receptor blockers in
      nephropathy from type 2 diabetes.
AB  - Type 2 diabetes is the most common cause of end-stage renal disease in the United
      States, and type 2 diabetes has been shown to be a myocardial infarction
      equivalent in regard to risk of death from a cardiovascular event. Proteinuria is
      a surrogate marker for renal disease progression, and although data favor both
      the angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor
      blockers (ARBs) in reducing proteinuria, data for renal outcomes, such as time to
      dialysis, only exist for the ARBs, which clearly increase the duration to
      dialysis. Conversely, ACE inhibitors have overwhelming data that show substantial
      risk reduction from cardiovascular events and death in people with type 2
      diabetes. Similar data on cardiovascular risk reduction are not yet available
      with ARBs, although two trials of renal disease progression did have
      cardiovascular endpoints as secondary outcomes. There were no significant
      differences between the ARB and control group except for first hospitalization
      with heart failure, where losartan reduced the risk by 32%, but there was a
      trend, albeit not significant, toward reduction of myocardial infarction. The
      first information regarding ARB effects on cardiovascular events as primary
      outcomes will come from the Losartan Intervention for Endpoint (LIFE) Reduction
      in Hypertension study. Therefore, as of this writing, all patients with type 2
      diabetes and no evidence of nephropathy, ie, proteinuria and an elevated
      creatinine > 1.5 mg/dL, should be placed on an ACE inhibitor for cardiovascular
      risk reduction. If nephropathy is present, the evidence would support an ARB for
      therapy in concert with a b-blocker for cardiovascular risk reduction and
      renoprotection.

PMID- 12003700
TI  - The use of calcium antagonists in the treatment of hypertensive persons with
      kidney disease.
AB  - The treatment of hypertension is proven to reduce cardiovascular and renal risk.
      Combination drug therapy is becoming recognized as a necessity in most patients
      with hypertension and kidney disease. Allegations about the safe use of calcium
      antagonists in patients with kidney disease have led to questions and confusion
      about their use in this common condition. This article reviews the cardiovascular
      and renal safety of the long-acting calcium antagonists from studies comparing
      calcium antagonists with placebo and with angiotensin converting enzyme
      inhibitors or angiotensin receptor blockers in patients with kidney disease and
      hypertension. Patients with proteinuria and kidney disease should have their
      blood pressure brought as close to target (< 130/80 mm Hg) as possible for
      cardiovascular and renal protection. Lowering blood pressure in this setting will
      require an average of three antihypertensive agents. In patients with
      hypertension and proteinuria, angiotensin converting enzyme inhibitors or
      angiotensin receptor blockers must be part of the regimen, and calcium
      antagonists are safe and effective in this condition when used with them in
      combination.

PMID- 12003702
TI  - Effects of antihypertensive therapy on sexual activity in hypertensive men.
AB  - Sexual dysfunction has a high prevalence among hypertensive men, and hypertension
      per se, regardless of drugs, has been suggested to affect sexual function. The
      available studies have not clarified which factors play a major role in the
      pathogenesis of sexual dysfunction in hypertensive men. Neurovascular factors,
      however, seem to be especially important, (in particular defective nitric oxide
      activity), although hormonal and psychogenic factors cannot be excluded. Further
      studies are needed to answer the important question of whether erectile
      dysfunction seen in hypertension may be one expression of vascular disease and
      target organ damage. The incidence of sexual dysfunction is exacerbated by
      antihypertensive drug treatment. There is evidence that some classes of drugs,
      such as diuretics, centrally acting sympatholytic drugs, and b-blockers have a
      greater impact on sexual function than other classes, such as calcium antagonists
      and angiotensin converting enzyme inhibitors. Present evidence on the effects of
      angiotensin II antagonists is limited, but some data suggest that sexual function
      in men receiving these drugs not only is not altered, but even improves. Since
      sexual function is an important aspect of quality of life for the individual, it
      is important in treating hypertension to ensure that the drugs used have the
      lowest possible potential for causing sexual problems. This ensures the best
      balance between therapeutic efficacy and quality of life, which is essential for
      compliance.

PMID- 12003701
TI  - Carcinogenicity of antihypertensive therapy.
AB  - Several studies have suggested that antihypertensive treatment may promote cancer
      through unknown mechanisms. Early retrospective studies implicated reserpine in
      breast cancer, but data from prospective studies and meta-analysis of several
      case-controlled studies showed only a weak association between reserpine and
      breast cancer which, although statistically significant, is of little clinical
      concern. Data from case-controlled studies and several cohort studies suggested
      an association between the use of a diuretic and the occurrence of renal cell
      cancer, particularly in women. A recent study showed an association between the
      use of a diuretic and the occurrence of colon cancer. Several prospective studies
      showed that treatment with atenolol may increase mortality from malignancy.
      However, other studies that analyzed data from several thousand patients could
      not confirm this association. In three prospective and a few case-controlled
      studies, angiotensin converting enzyme inhibitors were not associated with
      increased mortality from malignancy. In addition, a recent retrospective study
      showed that long-term use of angiotensin converting enzyme inhibitors had a
      protective effect against malignancy. Data from three large case-controlled
      studies and the combined data from eight randomized controlled studies and seven
      longitudinal studies showed a similar risk for malignancy among users and
      nonusers of calcium antagonists. Until further data from prospective clinical
      trials are available, we advise caution about long-term diuretic therapy in
      women. With regard to other antihypertensive drug classes, we suggest continuing
      the management of hypertension according to current treatment guidelines with
      little fear of any substantial cancer risk.

PMID- 12003703
TI  - Antihypertensive drugs and cognitive function.
AB  - The increase in life expectancy is associated with a sharp rise in cognitive
      disorders, particularly after the age of 80 years. The identification and
      management of risk factors for these invalidating and distressing conditions must
      be considered a priority. Hypertension has been shown to carry an increased risk
      not only for cerebrovascular morbidity and mortality, but also for cognitive
      impairment and dementia. The fact that antihypertensive treatment has been
      demonstrated to decrease those risks offers a new opportunity to reduce the
      prevalence of such related disorders and to promote healthy aging.

PMID- 12003704
TI  - Do angiotensin receptor antagonists have benefits beyond blood pressure lowering?

PMID- 12003705
TI  - Resistant hypertension.
AB  - Recent clinical trials suggest that resistant hypertension is increasingly
      common. In the majority of patients, uncontrolled hypertension is due to
      persistent elevation of the systolic blood pressure. Older age and obesity are
      associated with poor blood pressure control. Other contributing factors include
      severity of the underlying hypertension and renal insufficiency. Poor patient
      adherence is thought be a common cause of medication resistance. Exogenous
      substances such as nonsteroidal anti-inflammatory drugs, oral contraceptives, and
      sympathomimetic agents can interfere with treatment. The prevalence of secondary
      causes of hypertension increases with age, especially atherosclerotic renal
      artery stenosis. Recent reports suggest that primary aldosteronism may be the
      most common secondary cause of hypertension. It should be considered in all
      patients with resistant hypertension. Effective treatment of resistant
      hypertension requires identification and reversal of contributing factors and/or
      secondary causes of hypertension. Pharmacologic therapy should utilize
      combination therapy, including a long-acting diuretic.

PMID- 12003706
TI  - Sympathetic nervous system function in renal hypertension.
AB  - Hypertension is a common complication of chronic renal failure, accelerating the
      deterioration in renal function and constituting an important risk factor for the
      excessive cardiovascular morbidity and mortality. However, there are large gaps
      in our understanding of the pathogenesis and treatment of renal hypertension.
      Although this hypertension traditionally is thought to be largely volume
      dependent, an increasing body of literature suggests that there is an important
      sympathetic neural component. Microneurographic studies have demonstrated
      sympathetic overactivity without baroreflex impairment in both hypertensive
      chronic hemodialysis patients as well as in those with less advanced renal
      insufficiency. In a small group of patients with moderate chronic renal
      insufficiency and renin-dependent hypertension, sympathetic overactivity was
      normalized during antihypertensive monotherapy with the angiotensin converting
      enzyme inhibitor enalapril, but exacerbated by antihypertensive therapy with the
      dihydropyridine calcium channel blocker amlodipine. These results implicate a
      potentially important role for the sympathetic nervous system in explaining
      recent trial data suggesting an added renoprotective effect of antihypertensive
      agents that block the renin-angiotensin system. Future clinical trials are needed
      to determine whether normalization of sympathetic activity should constitute an
      important therapeutic goal to improve renal and cardiovascular outcomes in
      patients with chronic renal failure.

PMID- 12003708
TI  - Functional tests for primary aldosteronism: value of captopril suppression.
AB  - With the introduction of more simple screening tests such as the
      aldosterone/renin ratio, the detection rate of primary aldosteronism has
      increased considerably. Until now, no reference values have been available for
      reporting the aldosterone/renin ratio using plasma aldosterone values expressed
      in SI units (pmol/L) and plasma active renin (ng/L) measured by immunoradiometric
      assay. We studied 153 subjects who had either normal blood pressure, essential
      hypertension, or primary aldosteronism. Essential hypertensive patients usually
      have aldosterone/renin (pmol/L/ng/L) ratios below 100, whereas ratios for
      patients with primary aldosteronism are above 140. Results that fall between 100
      and 140 suggest a need for repeat testing. Patients with elevated
      aldosterone/renin ratios require confirmatory testing to demonstrate
      nonsuppressive autonomous aldosterone production. To this end, salt loading is
      widely used, but this approach may be contraindicated in patients with severe
      hypertension. The captopril suppression test appears as effective as salt loading
      in confirming a diagnosis of primary aldosteronism. In addition, the captopril
      test is safe, well tolerated, and cost-effective.

PMID- 12003707
TI  - Dopamine receptor-coupling defect in hypertension.
AB  - Dopamine synthesized in non-neural tissues, eg, renal proximal tubule, functions
      in an autocrine or paracrine manner. The effects of dopamine are transduced by
      two classes of receptors (D1- and D2-like) that belong to the superfamily of G
      protein-coupled receptors. In genetic hypertension, the D1 receptor, a member of
      the D1-like receptor family, is uncoupled from its G protein complex, resulting
      in a decreased ability to regulate renal sodium transport. The impaired D1
      receptor/G protein coupling in renal proximal tubules in genetic hypertension is
      secondary to abnormal phosphorylation and desensitization of the D1 receptor
      caused by activating single nucleotide polymorphisms of a G protein-coupled
      receptor kinase, GRK type 4.

PMID- 12003709
TI  - Choice of biochemical test for diagnosis of pheochromocytoma: validation of
      plasma metanephrines.
AB  - Pheochromocytomas, although a rare cause of hypertension, are dangerous tumors
      that require consideration among large numbers of patients. The subsequent low
      prevalence of the tumor among those tested and inadequacies of commonly used
      biochemical tests make excluding or confirming the tumor an often difficult and
      time consuming task. Recognition that catecholamines are metabolized to free
      metanephrines within pheochromocytoma tumor cells, and that this process is
      independent of catecholamine release, provides a rationale for use of these
      metabolites in the biochemical diagnosis of pheochromocytoma. Measurements of
      plasma concentrations of free metanephrines thereby promise more reliable and
      efficient diagnosis of pheochromocytoma than offered by conventional biochemical
      tests.

PMID- 12003710
TI  - Neurogenic factors in renal hypertension.
AB  - Hypertension is very common in patients with chronic renal failure and
      contributes to cardiovascular morbidity and mortality. Several mechanisms may
      contribute to hypertension in these patients, but recently a large body of
      evidence supports the notion that activation of the sympathetic nervous system
      (SNS) may play a very important role. In rats with 5/6 nephrectomy, the turnover
      rate of norepinephrine was increased in brain nuclei involved in the
      noradrenergic control of blood pressure, and dorsal rhizotomy prevented
      hypertension. Studies in human subjects with chronic renal failure and
      hypertension have also shown increased peripheral SNS activity measured my
      microneurography in the peroneal nerve and normalization with nephrectomy. In
      all, these studies indicate that renal injuries may activate renal afferent
      pathways that connect with integrative brain structures in SNS activity and blood
      pressure. We have also shown that central SNS activity is modulated by local
      expression of nitric oxide, which, in turn, is regulated by interleukin-1b.

PMID- 12003711
TI  - Cancer in Inflammatory Bowel Disease.
AB  - Colorectal cancer (CRC) is a complication in both patients with longstanding
      ulcerative colitis and those with Crohn's disease. As with sporadic CRC, surgical
      therapy (with adjuvant chemotherapy in advanced disease) is the only effective
      treatment. Identifying risk factors for CRC in inflammatory bowel disease (IBD)
      should allow patients to receive appropriate medical, endoscopic, and surgical
      care to minimize CRC morbidity and mortality. Total proctocolectomy remains the
      most effective form of cancer prophylaxis in IBD patients, but because of the
      impact of this approach and the low absolute risk of cancer, clinicians seldom
      recommend it. Colonoscopic surveillance with systematic biopsies is used to
      detect mucosal dysplasia and thus identify those patients at greatest risk for
      developing CRC. Patients with dysplasia other than that in readily excised polyps
      should be referred for surgery. Although fraught with limitations, surveillance
      is the best method currently available for reducing CRC mortality and morbidity
      short of prophylactic colectomy. It will have to remain the standard of practice
      until better diagnostic tests are available. Surveillance should be offered and
      performed in the same manner for patients with Crohn's disease and ulcerative
      colitis. Chemoprevention may prove effective in the future, but currently used
      agents have only a modest benefit, if any. Adenocarcinoma of the small intestine
      occurs at an increased rate in patients with Crohn's disease of the bowel with
      longstanding small bowel involvement, but there are no current methods of early
      detection. Treatment is based on disease identified from evaluation of symptoms
      or incidental finding. Some extraintestinal cancers have been noted to occur at
      increased rates in series from referral centers but not in population-based
      studies.

PMID- 12003712
TI  - Metabolic Bone Disease in Inflammatory Bowel Disease.
AB  - An oral calcium supplement (1000 mg/day) is recommended. Regular exercise should
      be performed. Ethanol intake should be moderate. Protein intake should be
      moderate. The patient's vitamin D status should be determined and corrected with
      an oral supplement when deficiency is present. Baseline and yearly bone density
      measurement should be taken. Alendronate, 10 mg/d orally, or risedronate, 5 mg/d
      orally, should be given to patients with osteopenia. Use of corticosteroids,
      cyclosporin, tacrolimus, and methotrexate should be limited to the short term
      when possible. Estrogen replacement therapy is recommended in postmenopausal
      women unless contraindications exist.

PMID- 12003713
TI  - Inflammatory Bowel Disease in Children.
AB  - Crohn's disease and ulcerative colitis remain medically incurable conditions with
      potentially significant morbidity. The treatment of children with these
      conditions therefore should seek to reduce or eliminate symptoms, optimize
      nutritional status, promote normal growth and development, prevent complications,
      and minimize the potential psychologic effects of chronic illness. Treatment
      strategies must seek to both induce and maintain clinical remission. For all but
      the most mildly affected children with Crohn's disease, a combination of
      nutritional and pharmacologic approaches is optimal. For those with ulcerative
      colitis, anti-inflammatory medication is necessary. Moderate to severe Crohn's
      disease acutely responds best to potent immunomodulatory therapy, eg,
      corticosteroids and infliximab. Either agent must be coupled with 6
      mercaptopurine or azathioprine to maintain long-term remission and to minimize
      toxicity. Particular attention must be paid to limit the growth suppression and
      other toxic effects of corticosteroids. Elemental or semielemental enteral
      nutrition also can induce remission effectively, but relapse is common after
      primary nutritional therapy is discontinued, mandating concomitant pharmacologic
      therapy with either 6-mercaptopurine or azathioprine. The availability of 6
      mercaptopurine/azathioprine metabolite testing allows optimization of
      immunomodulatory therapy, detection of noncompliance, and avoidance of
      potentially dangerous toxicity. Mild ulcerative colitis acutely responds to
      treatment with a 5-aminosalicylate medication. Long-term remission frequently can
      be maintained with the same medication. Moderate to severe disease activity
      requires potent immunomodulatory therapy if colectomy is to be avoided. Surgery
      is a potential cure for patients with ulcerative colitis, although the
      development of pouchitis after ileal pouch anal anastomosis is common and
      frequently requires long-term medical management. Surgery provides only
      palliative relief of complications in those with Crohn's disease. Emerging
      therapies, especially evolving biologic and probiotic agents, offer hope for
      better treatments in the years ahead.

PMID- 12003714
TI  - Perianal Crohn's Disease.
AB  - Perianal Crohn's disease usually is associated with involvement of another
      primary site of Crohn's disease. However, there is conflicting evidence on the
      relationship between proximal disease activity and perianal symptoms. Therefore,
      although it is reasonable to treat active proximal disease, symptomatic perianal
      disease may have to be treated on its own right. Hemorrhoids and anal fissures
      are best treated medically. Fistulae and abscesses are treated with control of
      sepsis and resolution of inflammation while preserving continence and quality of
      life. Abscesses require surgical drainage, which needs to be prolonged for
      healing to be complete. Fistulae may be treated with medications first,
      especially if the rectum is diseased. Refractory fistulae respond better to
      surgical treatment and sometimes require fecal diversion. The medical management
      of patients with perianal Crohn's disease consists of rectal mesalamine, systemic
      antibi-otics, immunosuppressive agents, and infliximab. The role of infliximab is
      evolving and it may reduce the need for surgical intervention in some cases.
      Perianal hygiene and skin protection help to reduce local discomfort.

PMID- 12003715
TI  - Inflammatory Bowel Disease: Future Therapies.
AB  - Current medical therapies for people with inflammatory bowel disease are not
      satisfactory, and it is unlikely that improvement of traditional drugs will have
      a major clinical impact. The immunopathogensis of Crohn's disease and ulcerative
      colitis are rapidly being deciphered, which is providing oppurtunities for
      radically innovative therapeutic approaches.

PMID- 12003717
TI  - Bleeding Angiodysplasia of the Colon.
AB  - Angiodysplasia should be considered in the differential diagnosis of
      hematochezia, gastrointestinal bleeding of obscure origin, and chronic iron
      deficiency anemia. Although the current medical literature lacks well-designed
      studies of the various therapeutic modalities, several conclusions appear
      warranted. Diagnosis of the bleeding site during colonoscopy and the use of
      endoscopic hemostasis techniques (electrocautery or laser) controls bleeding and
      may prevent rebleeding. When rebleeding occurs, it may be from the previously
      treated site or a different location. Estrogen-progestin therapy has not been
      shown effective in controlled trials but is used when other options fail. Surgery
      should be considered only when endoscopic therapy fails and the site of bleeding
      is localized. With all therapies, patients should be cautioned regarding the risk
      of recurrent bleeding.

PMID- 12003716
TI  - Nonsurgical Therapy for Solitary Rectal Ulcer Syndrome.
AB  - The treatment of solitary rectal ulcer syndrome (SRUS) remains problematic and is
      less than ideal. Prospective, well-designed studies assessing the efficacy of
      treatment for SRUS are few; most of the knowledge imparted for treating SRUS is
      experiential. As such, firm treatment recommendations can not be made. Rather, a
      conservative, stepwise, individualized approach must be employed. Diagnostic
      modalities should be incorporated in the management scheme to direct treatment
      when indicated. Management must include patient reassurance that the underlying
      lesion is benign, because complete "cures" are uncommon in those with SRUS. The
      goals of therapy should be discussed with the patient prior to initiating
      treatment. Although the ultimate goal is macroscopic and microscopic healing, a
      realistic goal is cessation or minimization of symptoms. We outline a reasonable
      approach to the management of SRUS. Histologic confirmation of SRUS should prompt
      a discussion of the presumed pathogenic mechanisms with the patient. Conservative
      therapy with dietary fiber, bowel retraining, and bulk laxatives should be
      employed. If symptoms persist, the patient should receive a trial of sucralfate
      enemas for 6 weeks. Individuals who respond should continue conservative therapy.
      However, if symptoms persist, defecography can be done to assess for
      inappropriate puborectalis contraction and occult rectal mucosal prolapse.
      Patients with inappropriate contraction of the puborectalis can be offered
      biofeedback. Patients with occult rectal mucosal prolapse can be considered for
      surgery. However, the risks, benefits, and success rates of surgery should be
      discussed at length, prior to any procedure being performed. Rectopexy or
      Delorme's procedure offer the best success rates to date; however, the choice of
      surgical procedure must take into account the experience of the surgeon and
      wishes of the patient.

PMID- 12003718
TI  - Surgical Therapy for Colitis Cystica Profunda and Solitary Rectal Ulcer Syndrome.
AB  - The initial treatment for patients with colitis cystica profunda is aimed at re
      education of bowel habits to avoid straining. Patients are instructed to spend
      the minimum time on the commode. A high-fiber diet with bulk laxatives is
      recommended. If fiber does not work, polyethylene glycol solutions and surface
      active stool softeners such as docusate sodium are tried. Conservative therapy
      resolves most symptoms. Biofeedback is offered to patients who fail dietary
      therapy. For patients with associated rectal prolapse, an operation designed to
      correct the intussusception is considered. For full-thickness prolapse
      (procidentia) a mucosal resection (Delorme) or perineal proctectomy (Altemeier)
      is recommended. Surgical treatment of internal (occult) prolapse is problematic.
      If attempted, a resection and suture rectopexy has the most support. In the
      absence of procidentia, transanal excision may be used in selected patients. If
      other measures fail, a mucosal sleeve resection with coloanal pull-through or a
      diverting colostomy may be considered.

PMID- 12003719
TI  - Vascular Thoracic Outlet Syndrome.
AB  - Vascular thoracic outlet syndrome generally affects young, active, otherwise
      healthy patients. The diagnosis is suspected by clinical presentation, and can be
      confirmed with angiography or venography. Conservative management has been
      associated with significant morbidity and long-term residual disability. We have
      used a multimodal treatment protocol that includes thrombolysis, anticoagulation,
      surgical decompression, and interventional procedures. Catheter-directed
      recombinant tissue-type plasminogen activator and intravenous heparin infusion
      are instituted at the time of diagnosis to promote recanalization and prevent
      propagation of thrombus. Surgical decompression of the thoracic outlet can be
      readily achieved by first rib resection during the same hospitalization.
      Postoperative venograms are obtained in all patients. Residual stenoses can be
      managed with angioplasty alone in some patients but more commonly require stent
      placement. We believe thrombolysis, anticoagulation, surgical decompression, and
      percutaneous interventions act synergistically to improve results of therapy in
      patients with vascular thoracic outlet syndrome.

PMID- 12003720
TI  - Erythromelalgia.
AB  - No treatment is consistently effective in the management of patients with
      erythromelalgia. There is a dearth of adequate studies examining the response of
      erythromelalgia to therapy. Most recommendations are suggested based on case
      reports, small case series, and anecdotal reports. The management of
      erythromelalgia is difficult and frequently involves a multidisciplinary
      approach. An approach to management of individuals with erythromelalgia includes
      patient education, learning to avoid episodes relieving discomfort of the
      episodes, controlling secondary and underlying factors, and use of drugs used to
      control erythromelalgia.

PMID- 12003721
TI  - Deep Venous Thrombosis and Pulmonary Embolism.
AB  - Venous thromboembolic disease, including deep venous thrombosis (DVT) and
      pulmonary embolism (PE), is an under-diagnosed and under-appreciated medical
      problem that results in significant patient morbidity and mortality. Inadequate
      venous thromboprophylaxis in surgical as well as medically ill patients results
      in DVT and PE that negatively impact patient outcomes and increase health-care
      costs. A high index of clinical suspicion combined with an evidence-based use of
      diagnostic tests helps identify patients with acute thrombosis. Failure to
      accurately and promptly diagnose and treat DVT and PE can result in excess
      morbidity and mortality due to postthrombotic syndrome, pulmonary hypertension,
      and recurrent thrombosis. Conversely, unnecessary anticoagulation provides risk
      in the absence of any tangible benefit. The immediate commencement of parenteral
      anticoagulant therapy with intravenous unfractionated heparin or a subcutaneous
      low molecular weight heparin (LMWH) upon presentation with DVT or PE (often even
      before objective diagnosis confirmation) is necessary to minimize propagation,
      embolization, and recurrence rates. We favor weight-based LMWH therapy in most of
      our patients with DVT because of the ability to treat exclusively or primarily in
      the outpatient setting. We still admit patients with PE for a minimum duration of
      2 days for close observation. Subsequent conversion to oral anticoagulation with
      warfarin (target INR of 2.0 to 3.0 in most patients) should include an overlap
      with parenteral therapy of at least 4 to 5 days and until a stable target INR has
      been achieved. A minimum of 3 to 6 months of anticoagulation is recommended
      following a first episode of idiopathic DVT and any PE. A shorter course of
      therapy may be sufficient following a situational (eg, after surgery and
      postpartum) or calf DVT. Long-term, and at times lifelong, therapy should be
      considered in patients with thrombosis in the setting of a persistent acquired or
      inherited hypercoagulable state. Thrombolytic therapy probably should be reserved
      for young patients with iliofemoral DVT, any patient with a threatened limb due
      to impending venous limb gangrene, and those with PE who have objective evidence
      of cardiopulmonary compromise. Unfavorable risk-to-benefit and cost-to-benefit
      ratios make more extensive use of thrombolytics undesirable. The prevention of
      the postthrombotic syndrome with fitted, graduated compression garments and age-
      and gender-appropriate cancer screening are indicated in all patients with DVT in
      an attempt to minimize morbidity and mortality. Hypercoagulable state testing is
      indicated when the results of individual tests will significantly impact the
      choice of anticoagulant, intensity of therapy, therapeutic monitoring, family
      screening, family planning, prognosis determination, and most of all, duration of
      therapy.

PMID- 12003722
TI  - Pseudoaneurysms.
AB  - Vascular complications that are the result of invasive diagnostic or therapeutic
      procedures requiring arterial access occur frequently. A common complication,
      pseudoaneurysm, has significant risk of expansion, extrinsic compression on
      native arteries, rupture, embolization, and infection. A pseudoaneurysm
      represents a persistent defect in the walls of the artery, resulting in
      extravasation of blood outside of the artery. This extravascular blood is
      confined to the surrounding soft tissues. Clinical suspicion and duplex
      ultrasonography are the primary diagnostic modalities. There are several options
      for treatment of pseudoaneurysms, including surgical repair and ultrasound-guided
      compression. However, a new therapeutic option, ultrasound-guided thrombin
      injection, has become the treatment of choice for pseudoaneurysms. This procedure
      is highly effective, rapid, and very safe. Using direct, real-time visualization
      of the pseudoaneurysm, a needle is inserted percutaneously into the
      pseudoaneurysm sac, and a small amount of dilute bovine thrombin is injected.
      Thrombosis of the sac is rapidly evident. Rare complications include
      thromboembolism into the native artery and hypersensitivity reaction to bovine
      thrombin.

PMID- 12003723
TI  - Aortitis.
AB  - Aortitis is defined as an inflammatory process that involves one or more layers
      of the aortic wall (internal elastic lamina, tunica media, and adventitia) and
      can be caused by multiple mechanisms. Clinical features are usually nonspecific
      and a high index of suspicion is required for making the diagnosis. Although
      noninvasive imaging studies are being increasingly used in evaluating patients
      for diagnosis, angiography remains the gold standard for confirming aortic
      involvement. When tissue is available, pathologic examination can aid in
      clarifying the diagnosis. Aortitis, irrespective of the underlying cause,
      frequently displays similar clinical, pathologic, and arteriographic features and
      therefore understandably presents a therapeutic and diagnostic dilemma. Whatever
      the cause, early identification and aggressive treatment is required in order to
      avert the potentially life-threatening sequelae. The treatment of aortitis is
      determined by the underlying cause. If diagnosed early, infectious aortitis
      responds to appropriate antimicrobial therapy, whereas noninfectious, immune
      mediated aortitis requires immunosuppressive therapy. However, in many instances,
      primarily because of the delay in diagnosis, surgical intervention is necessary
      to treat the associated anatomic and physiologic sequelae. Less definitive and
      more controversial is the role of inflammation in both primary and secondary
      accelerated atherosclerosis of the aorta and its modality of treatment.

PMID- 12003724
TI  - Atheroembolism.
AB  - The many manifestations of atheroembolism are apparent in all specialties.
      However, with increasing intervention in older patients with atherosclerotic
      disease, it has become an important renal clinical problem. Atheroembolic disease
      is widely recognized as a cause of acute catastrophic renal dysfunction and
      recent important data have suggested that effective management protocols can
      improve outcome. It is probable that the clinical course is insidious in the
      majority of patients with severe atherosclerotic aortic disease. The management
      of these patients is less clear and at present rests on small anecdotal reports.

PMID- 12003725
TI  - Hepatopulmonary Syndrome and Portopulmonary Hypertension.
AB  - In patients with hepatopulmonary syndrome, supplemental oxygen and liver
      transplantation are the usual treatments of choice. Pharmacologic approaches have
      limited success in improving hypoxemia. Interventional radiology procedures may
      improve arterial hypoxemia in highly selected patients. In patients with
      portopulmonary hypertension, continuous infusion with intravenous epoprostenol
      (prostaglandin I(2)) can significantly improve pulmonary hemodynamics. Outcome
      following liver transplantation is variable; increased cardiopulmonary mortality
      occurs in patients with moderate to severe pulmonary hypertension.

PMID- 12003726
TI  - [Surgical treatment of chronic pancreatitis].

PMID- 12003727
TI  - [A new model for medical care to multi-admitted patients].
AB  - BACKGROUND AND OBJECTIVE: Patients with chronic conditions are often readmitted
      to hospital. A study was designed to improve health care to these patients.
      PATIENTS AND METHODS: Patients attended at the Internal Medicine Department of a
      hospital area who were admitted to hospital at least three times in a year were
      included in the study. Within a prospective study, patients were attended by
      means of specific consultation with care upon request and telephone care, with
      the possibility of programmed admission. RESULTS: Patients were followed for 32
      months, with a 45% decrease in the admission rate, 50% in visits to the Emergency
      Department, and 26% in hospital stay days. CONCLUSIONS: The proposed care model
      decrease the attending needs for these patients.

PMID- 12003728
TI  - [Results of cephalic pancreaticoduodenectomy in patients with chronic
      pancreatitis].
AB  - OBJECTIVE: To analyse the results obtained after cephalic pancreatoduodenectomy
      in patients with severe chronic pancreatitis. DESIGN: Retrospective study of
      indications and results of the intervention.Patients. The inclusion criteria were
      severe anatomic alteration of the head of the pancreas associated with refractory
      pain. Pancreatoduodenectomy was performed in 19 patients. RESULTS: Four patients
      had postoperative morbidity, and the mean hospital stay was 15 days. One patient
      died in the postoperative period. The pain evolution after surgery was: total
      control in 72% and satisfactory control in the remaining patients. During follow
      up, de novo diabetes was detected in two patients, difficulty in maintaining
      weight in one patient, and de novo steatorrhea in four patients. CONCLUSIONS:
      Cephalic pancreatoduodenectomy is a good therapeutic alternative for the
      treatment of patients with chronic pancreatitis, refractory pain, and severe
      involvement of the pancreas head. Pain control is excellent and sequelae, such as
      diabetes or steatorrhea, are easily amenable to medical treatment.

PMID- 12003729
TI  - [Guidelines for action and diagnosis in atherothrombosis in Spain: ADA Study
      (Action and Diagnosis in Atherothrombosis)].
AB  - OBJECTIVE: The ADA Study was designed to know the usual action guidelines in
      Spain for the diagnosis and treatment in a cohort of patients who had a recent
      atherothrombotic event. PATIENTS AND METHODS: Cross-sectional, observational,
      multicenter epidemiologic study (294 hospitals) with a total of 3,512 patients
      enrolled. Patients had had an atherothrombotic event in the coronary or cerebral
      vascular territory in the previous month or were diagnosed of symptomatic
      peripheral arterial disease within the last 3 months. A total of 237
      investigators (155 cardiologists, 113 neurologists, and 79 vascular surgeons)
      participated in the study. RESULTS: 54.9% of patients in the study had a previous
      atherothrombotic event. Of these, 63.1% were on antithrombotic therapy; after the
      second episode, 2.6% of patients were on no preventive therapy. A great disparity
      and an excessive number of diagnostic tests was found to confirm the diagnosis of
      the current atherothrombotic event, which is in contrast with a small percentage
      of patients who had exams performed to confirm or rule out the atherothrombotic
      involvement in other vascular territories. CONCLUSIONS: An appropriate protocol
      should be established for the diagnosis and therapy of patients with the
      likelihood of having clinical manifestations due to an ahterothrombotic event.

PMID- 12003730
TI  - [Serotonin syndrome: report of a fatal case and review of the literature].
AB  - We report here the case of a patient with fluoxetine and selegiline induced
      serotonin syndrome, which presented as encephalopathy, generalized myoclonias,
      fever, stiffness and sweating, complicated with acute renal failure,
      rhabdomyolysis and disseminated intravascular coagulation findings. The patient
      died 6 days after admission. This syndrome is discussed, with an analysis of its
      causes, pathophysiology and therapy. A special emphasis is placed on the clinical
      issues and differential diagnosis with the malignant neuroleptic syndrome and
      other clinical entities with which it could be mistaken. General recommendations
      are provided to avoid this poorly characterized syndrome that, as in our patient,
      may have a fatal outcome.

PMID- 12003731
TI  - [Value of serum tumor markers for the early diagnosis of neoplasm and in health
      exams for asymptomatic persons].

PMID- 12003732
TI  - [Clinical application of fatty acids as modulating agents in immune functions].

PMID- 12003733
TI  - [Diagnostic attitudes in the pulmonary hemorrhage syndrome with renal
      involvement].

PMID- 12003734
TI  - [Clinical manifestations and immunology associated with chronic infection with
      hepatitis C virus].

PMID- 12003735
TI  - [Fever, headache, and lumbar pain].

PMID- 12003736
TI  - [Dermatitis in a patient with chronic myeloid leukemia].

PMID- 12003737
TI  - [Pleural effusion in a 16-year old patient].

PMID- 12003738
TI  - [Prolonged fever and cutaneous lesions in a 59-year old woman].

PMID- 12003739
TI  - [Renal polycystosis: a systemic disease?].

PMID- 12003740
TI  - [Cervicofacial subcutaneous emphysema as initial and single presenting form of
      complicated diverticulitis].

PMID- 12003741
TI  - [Hospital admissions and stays. Results: lost or absent patients?].

PMID- 12003742
TI  - [Hospital admissions and stays. Results: lost or absent patients?].

PMID- 12003743
TI  - [Nephrogenic diabetes insipidus secondary to chronic interstitial nephritis
      associated with mesalazine therapy].

PMID- 12003744
TI  - [Severe hyponatremia associated with the use of fluoxetine in the elderly].

PMID- 12003745
TI  - [Lipodystrophy syndrome associated with human immunodeficiency virus infection
      (II). Clinical and therapeutic issues].

PMID- 12003746
TI  - Social responsibility and research ethics in community-driven studies of
      industrialized hog production.
AB  - Environmental health research can document exposures and health effects that
      result from inequitable relationships between communities of low income or people
      of color and the institutions that derive benefits (profits, federal and state
      funding or services, avoidance of wastes) from activities and policies that
      burden these communities. Researchers, most of whom work in relatively privileged
      institutions, are placed in situations of conflicting loyalties if they conduct
      research in collaboration with, or on behalf of, communities burdened by
      environmental injustices. These conflicts can threaten the self-interest of
      researchers and may raise social and ethical issues that do not typically arise
      in research projects that respond to the agendas of institutions. This article
      describes how we addressed issues of research ethics and social responsibility in
      environmental health research on industrialized hog production in North Carolina.
      Researchers and institutional review boards are not well prepared to address
      ethical issues when interests of entire communities, as well as individual
      research participants, are involved. Community-driven research partnerships can
      help address problems in research ethics and can enhance the social
      responsibility of researchers and their institutions.

PMID- 12003747
TI  - How sustainable agriculture can address the environmental and human health harms
      of industrial agriculture.
AB  - The industrial agriculture system consumes fossil fuel, water, and topsoil at
      unsustainable rates. It contributes to numerous forms of environmental
      degradation, including air and water pollution, soil depletion, diminishing
      biodiversity, and fish die-offs. Meat production contributes disproportionately
      to these problems, in part because feeding grain to livestock to produce meat-
      instead of feeding it directly to humans--involves a large energy loss, making
      animal agriculture more resource intensive than other forms of food production.
      The proliferation of factory-style animal agriculture creates environmental and
      public health concerns, including pollution from the high concentration of animal
      wastes and the extensive use of antibiotics, which may compromise their
      effectiveness in medical use. At the consumption end, animal fat is implicated in
      many of the chronic degenerative diseases that afflict industrial and newly
      industrializing societies, particularly cardiovascular disease and some cancers.
      In terms of human health, both affluent and poor countries could benefit from
      policies that more equitably distribute high-protein foods. The pesticides used
      heavily in industrial agriculture are associated with elevated cancer risks for
      workers and consumers and are coming under greater scrutiny for their links to
      endocrine disruption and reproductive dysfunction. In this article we outline the
      environmental and human health problems associated with current food production
      practices and discuss how these systems could be made more sustainable.

PMID- 12003748
TI  - The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary
      review of scientific knowledge.
AB  - In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused
      an outbreak of a previously unrecorded condition, later known as toxic oil
      syndrome (TOS), clinically characterized by intense incapacitating myalgias,
      marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons
      affected, approximately 300 died shortly after the onset of the disease and a
      larger number developed chronic disease. For more than 15 years, a scientific
      committee supported by the World Health Organization's Regional Office for Europe
      and by the Institute of Health Carlos III in Madrid has guided investigation
      intended to identify the causal agent(s), to assess toxicity and mode of action,
      to establish the pathogenesis of the disease, and to detect late consequences.
      This report summarizes advances in research on this front. No late mortality
      excess has been detected. Among survivors, the prevalence of some chronic
      conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to
      reproduce the condition in laboratory animals have been unsuccessful, and no
      condition similar to TOS has been reported in the scientific literature.
      Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels
      of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with
      chemical analyses of case-related oils have shown that the disease is strongly
      associated with the consumption of oils containing fatty acid esters of 3-(N
      phenylamino)-1,2-propanediol (PAP). These chemicals have also been found in oils
      synthesized under conditions simulating those hypothesized to have occurred when
      the toxic oil was produced in 1981. Whether PAP esters are simply markers of
      toxicity of oils or have the capability to induce the disease remains to be
      elucidated.

PMID- 12003749
TI  - New fish-killing alga in coastal Delaware produces neurotoxins.
AB  - Ten fish mortality events, involving primarily Atlantic menhaden, occurred from
      early July through September 2000 in several bays and creeks in Delaware, USA.
      Two events involved large mortalities estimated at 1-2.5 million fish in Bald
      Eagle Creek, Rehoboth Bay. Samples from Indian Inlet (Bethany Beach), open to the
      Atlantic, as well as from an enclosed area of massive fish kills at nearby Bald
      Eagle Creek and Torque Canal were collected and sent to our laboratory for
      analysis. Microscopic examination of samples from the fish kill site revealed the
      presence of a single-cell Raphidophyte alga Chattonella cf. verruculosa at a
      maximum density of 1.04 x 10(7) cells/L. Naturally occurring brevetoxins were
      also detected in the bloom samples. Besides the Chattonella species, no other
      known brevetoxin-producing phytoplankton were present. Chromatographic,
      immunochemical, and spectroscopic analyses confirmed the presence of brevetoxin
      PbTx-2, and PbTx-3 and -9 were confirmed by chromatographic and immunochemical
      analyses. This is the first confirmed report in the United States of brevetoxins
      associated with an indigenous bloom in temperate Atlantic estuarine waters and of
      C. cf. verruculosa as a resident toxic organism implicated in fish kills in this
      area. The bloom of Chattonella continued throughout September and eventually
      declined in October. By the end of October C. cf. verruculosa was no longer seen,
      nor was toxin measurable in the surface waters. The results affirm that to avoid
      deleterious impacts on human and ecosystem health, increased monitoring is needed
      for brevetoxins and organism(s) producing them, even in areas previously thought
      to be unaffected.

PMID- 12003750
TI  - Exploring associations between residential location and breast cancer incidence
      in a case-control study.
AB  - Locating geographic hot spots of cancer may lead to new causal hypotheses and
      ultimately to new knowledge of cancer-causing factors. The Cape Cod region of
      Massachusetts has experienced elevated incidence of breast cancer compared with
      statewide averages. The origins of the excess remain largely unexplained, even
      after the Upper Cape Cod Cancer Incidence Study investigated numerous potential
      environmental exposures. Using case-control data from this study (258 cases and
      686 controls), we developed an exploratory approach for measuring associations
      between residential location and breast cancer incidence, adjusting for
      individual-level risk factors. We measured crude and adjusted odds ratios over
      the study region using fixed-scale grids and a smoothing algorithm of overlapping
      circular units. Polycircular hot spot regions, derived from the peak values of
      the smoothed odds ratios, delineated geographic areas wherein residence was
      associated with 60% [odds ratio (OR), 1.6; 95% confidence interval (CI), 0.8-3.2]
      to 210% (OR, 3.1; 95% CI, 1.3-7.2) increased incidence relative to the remainder
      of the study population. The findings suggest several directions for further
      research, including the identification of potential environmental exposures that
      may be assessed in forthcoming case-control studies.

PMID- 12003751
TI  - Assessment of lifestyle effects on the overall antioxidant capacity of healthy
      subjects.
AB  - Oxidative damage is increasingly recognized as playing an important role in the
      pathogenesis of several diseases such as cancer and cardiovascular diseases.
      Using a biologic test based on whole blood resistance to free-radical aggression,
      we sought to evaluate lifestyle factors that may contribute to the normal
      variability of the overall antioxidant status. We assessed this global
      antiradical defense capacity in 88 men and 96 women in relation to information on
      lifestyle obtained by questionnaire. In our relatively young, healthy population,
      we found a weak negative relation between male sex or aging and the resistance to
      oxidant stress. Among the factors studied, nonsmoking, vitamin and/or mineral
      supplementation, and regular physical activity were closely associated with an
      increased overall antioxidant capacity. Conversely, the antioxidant potential was
      negatively related to tobacco smoking; psychologic stress; alcohol consumption;
      moderate vegetable, low fruit, and low fish consumption; and, to a lesser extent,
      high natural ultraviolet light exposure. Thus, we were able to determine
      "unhealthy" and "healthy" lifestyle patterns that truly contributed to the
      variation of individual antioxidant capacity. We conclude that lifestyle
      determinants of cancer and cardiovascular risks were associated with a decreased
      overall antioxidant status as dynamically measured by means of a biologic test.
      Thus, the evaluation of the total human resistance against free-radical
      aggression, taking into account nutritional habits, lifestyle, and environmental
      factors, may be useful in preventive medicine as a precocious diagnosis to
      identify healthy subjects who are at risk for free-radical-mediated diseases.

PMID- 12003752
TI  - Personal exposure and long-term health effects in survivors of the union carbide
      disaster at bhopal.
AB  - Nine years after the Bhopal methyl isocyanate disaster, we examined the effects
      of exposures among a cross-section of current residents and a subset of those
      with persistent symptoms. We estimated individual exposures by developing
      exposure indices based on activity, exposure duration, and distance of residence
      from the plant. Most people left home after the gas leak by walking and running.
      About 60% used some form of protection (wet cloth on face, splashing water). Mean
      and median values of the exposure indices showed a declining trend with
      increasing distance from the plant. For those subjects reporting any versus no
      exposure, prevalence ratios were elevated for most respiratory and nonrespiratory
      symptoms. We examined exposure-response relationships using exposure indices to
      determine which were associated with health outcomes. The index total exposure
      weighted for distance was associated with most respiratory symptoms, one measure
      of pulmonary function in the cross-sectional sample [mid-expiratory flow (FEF)(25
      75), p = 0.02], and two measures of pulmonary function in the hospitalized subset
      [forced expiratory volume (FEV)(1), p = 0.02; FEF(25-75), p = 0.08). Indices that
      correlated with FEV(1) and forced vital capacity in the hospitalized subset did
      not correlate with the cross-sectional sample, and most indices (except total
      exposure) that correlated with the hospitalized subset did not correlate with the
      cross-sectional sample. Incorporation of distance into every index increased the
      number of symptoms associated; an improvement was also noted in the strength of
      the association for respiratory symptoms, but not for pulmonary function. The sum
      of duration (p = 0.02) and total exposure (p = 0.03) indices independently
      demonstrated stronger associations with percent predicted FEF(25-75) than the
      distance variable (p = 0.04). The results show that total exposure weighted for
      distance has met the criteria for a successful index by being associated with
      most respiratory symptoms as well as FEF(25-75), features of obstructive airways
      disease.

PMID- 12003753
TI  - ApoE genotype, past adult lead exposure, and neurobehavioral function.
AB  - Our objective in this study was to determine if the known relation between tibia
      bone lead levels and neurobehavioral test scores are influenced by the
      apolipoprotein E (ApoE) genotype. We collected data on 20 neurobehavioral tests
      in 529 former organolead workers who had an average of 16 years since last
      occupational exposure to lead. We used linear regression to model the relations
      between each of 20 neurobehavioral test scores and tibia lead, a binary variable
      for ApoE genotype (i.e., at least one Epsilon4 allele vs. none), and an
      interaction term between tibia lead and the binary term for ApoE genotype. At the
      time of testing, former lead workers were an average of 57.6 years of age; 82%
      were younger than 65 years. In regression analysis, we observed one statistically
      significant and one borderline significant coefficient for ApoE genotype alone.
      Coefficients for the ApoE and tibia lead interaction term were negative in 19 of
      the 20 regression models. This indicates that the slope for the relation between
      tibia lead and each neurobehavioral test was more negative for individuals with
      at least one Epsilon4 allele than for those who did not have an Epsilon4 allele.
      Four of 19 negative coefficients for the interaction term were statistically
      significant (digit symbol, Purdue pegboard assembly, Purdue pegboard-dominant
      hand, complex reaction time); another three of the remaining 16 coefficients
      (symbol digit, trail-making A, Stroop) were borderline significant (i.e., p <
      0.10). This study suggests that individuals may vary in susceptibility to the
      long-term effects of lead on the central nervous system (CNS). In particular, the
      persistent CNS effect of lead may be more toxic in individuals who have at least
      one ApoE-Epsilon4 allele.

PMID- 12003754
TI  - Residential pesticide use during pregnancy among a cohort of urban minority
      women.
AB  - Residential pesticide use is widespread in the United States. However, data are
      limited specific to use among minority populations. Nor are data available on the
      extent of pesticide exposure resulting from residential use during pregnancy. We
      have gathered questionnaire data on pesticide use in the home during pregnancy
      from 316 African-American and Dominican women residing in northern Manhattan and
      the South Bronx. Additionally, 72 women underwent personal air monitoring for 48
      hr during their third trimester of pregnancy to determine exposure levels to 21
      pesticides (19 insecticides and 2 fungicides). Of the women questioned, 266 of
      314 (85%) reported that pest control measures were used in the home during
      pregnancy; 111 of 314 (35%) reported that their homes were sprayed by an
      exterminator, and of those, 45% said the spraying was done more than once per
      month. Most (>or= 90%) of the pesticide was used for cockroach control. Use of
      pest control measures increased significantly with the level of housing disrepair
      reported. Of the women monitored, all (100%) had detectable levels of three
      insecticides: the organophosphates diazinon (range, 2.0-6,010 ng/m3) and
      chlorpyrifos (range, 0.7-193 ng/m3) and the carbamate propoxur (range, 3.8-1,380
      ng/m3), as well as the fungicide o-phenylphenol (range, 5.7-743 ng/m3). We also
      frequently detected the following four insecticides (47-83% of samples) but at
      lower concentrations: the pyrethroid trans-permethrin, piperonyl butoxide (an
      indicator of exposure to pyrethrins), and the organochlorines 1,1,1-trichloro-2,2
      bis(p-chlorophenyl)ethane and chlordane. Thirty percent of the women had
      detectable levels of all eight pesticides. Exposures were generally higher among
      African Americans than among Dominicans. We detected other pesticides in <or= 10%
      of samples. Results show widespread prenatal pesticide use among minority women
      in this cohort. Diazinon exposures for some women may have exceeded health-based
      levels, and our findings support recent federal action to phase out residential
      use of this insecticide.

PMID- 12003755
TI  - Reproducibility of urinary phthalate metabolites in first morning urine samples.
AB  - Phthalates are ubiquitous in our modern environment because of their use in
      plastics and cosmetic products. Phthalate monoesters--primarily monoethylhexyl
      phthalate and monobutyl phthalate--are reproductive and developmental toxicants
      in animals. Accurate measures of phthalate exposure are needed to assess their
      human health effects. Phthalate monoesters have a biologic half-life of
      approximately 12 hr, and little is known about the temporal variability and daily
      reproducibility of urinary measures in humans. To explore these aspects, we
      measured seven phthalate monoesters and creatinine concentration in two
      consecutive first-morning urine specimens from 46 African-American women, ages 35
      49 years, residing in the Washington, DC, area in 1996-1997. We measured
      phthalate monoesters using high-pressure liquid chromatography followed by tandem
      mass spectrometry on a triple quadrupole instrument using atmospheric pressure
      chemical ionization. We detected four phthalate monoesters in all subjects, with
      median levels of 31 ng/mL for monobenzyl phthalate (mBzP), 53 ng/mL for monobutyl
      phthalate (mBP), 211 ng/mL for monoethyl phthalate (mEP), and 7.3 ng/mL for
      monoethylhexyl phthalate (mEHP). These were similar to concentrations reported
      for other populations using spot urine specimens. Phthalate levels did not differ
      between the two sampling days. The Pearson correlation coefficient between the
      concentrations on the 2 days was 0.8 for mBP, 0.7 for mEHP, 0.6 for mEP, and 0.5
      for mBzP. These results suggest that even with the short half-lives of
      phthalates, women's patterns of exposure may be sufficiently stable to assign an
      exposure level based on a single first morning void urine measurement.

PMID- 12003756
TI  - An epidemiologic study to screen for chronic myelocytic leukemia in war victims
      exposed to mustard gas.
AB  - Chemical agents such as mustard gas (or sulfur mustard), which has alkylating
      characteristics, were used against Iranian combatants in the Iraq-Iran war.
      Previous studies have not shown a strong link between these chemical agents and
      the development of chronic myelocytic leukemia (CML). The purpose of this study
      was to evaluate the increased risk of CML development in Iranian soldiers exposed
      to mustard gas during the war. Based on a descriptive study of 2,500 cases with
      documented exposure to various chemical warfare agents, 665 patients had
      documented exposure to mustard gas. We screened the latter using the leukocyte
      alkaline phosphatase (LAP) test and performed further cytochemical studies on
      cases with positive results. From among the 665 cases with documented exposure to
      mustard gas, 9 cases had LAP scores < 20; 2 of these 9 cases had CML and a score
      of zero (0.3%). We detected cytogenetic abnormalities in 7 patients with low LAP
      scores and atypical lymphocytes of 5-11% in 40 patients. The risk ratio of CML
      developing in victims exposed to mustard gas (cutaneous or respiratory) may be
      higher in comparison with the normal population, although confounding factors
      (e.g., the possibility of exposure to combined chemical agents, excluding
      patients who did not manifest blisters) limited our results. Because the
      increased development of CML in young patients with a documented history of
      exposure to mustard gas cannot be disregarded, further studies are needed.

PMID- 12003757
TI  - Inorganic mercury and methylmercury in placentas of Swedish women.
AB  - We determined levels of inorganic mercury (I-Hg) and methylmercury in placentas
      from 119 Swedish women, not selected with respect to high exposure of mercury.
      Our objective was to relate placental Hg species with maternal and fetal blood
      concentrations and to evaluate possible associations with selenium. We performed
      the analyses using automated alkaline solubilization/reduction and cold-vapor
      atomic fluorescence spectrophotometry. I-Hg levels in placenta increased with an
      increasing number of maternal dental amalgam fillings (p < 0.001). Despite
      placental accumulation (median, 1.3 microg/kg; range, 0.18-6.7 microg/kg wet
      weight), a substantial fraction of maternal blood I-Hg, probably as Hg(0),
      reached the fetus. Although MeHg transferred easily to the fetus, it also
      accumulated in the placenta. On average, 60% of placental Hg was in the form of
      MeHg. The median concentration was 1.8 microg/kg (range, 0-6.2 microg/kg wet
      weight), more than twice the maternal blood concentration. We found significant
      associations between MeHg and selenium in both maternal and umbilical cord blood
      but not in the placenta. The associations were particularly obvious in freshwater
      fish consumers, probably reflecting that fish is a source of both MeHg and
      selenium. We found no correlations between I-Hg and selenium. This study
      increases the understanding of Hg, in its different forms, in human placenta and
      how they are related to maternal and fetal exposure.

PMID- 12003758
TI  - First National Survey of Lead and Allergens in Housing: survey design and methods
      for the allergen and endotoxin components.
AB  - From July 1998 to August 1999, the U.S. Department of Housing and Urban
      Development and the National Institute of Environmental Health Sciences conducted
      the first National Survey of Lead and Allergens in Housing. The purpose of the
      survey was to assess children's potential household exposure to lead, allergens,
      and bacterial endotoxins. We surveyed a sample of 831 homes, representing 96
      million permanently occupied, noninstitutional housing units that permit resident
      children. We administered questionnaires to household members, made home
      observations, and took environmental samples. This article provides general
      background information on the survey, an overview of the survey design, and a
      description of the data collection and laboratory methods pertaining to the
      allergen and endotoxin components. We collected dust samples from a bed, the
      bedroom floor, a sofa or chair, the living room floor, the kitchen floor, and a
      basement floor and analyzed them for cockroach allergen Bla g 1, the dust mite
      allergens Der f 1 and Der p 1, the cat allergen Fel d 1, the dog allergen Can f
      1, the rodent allergens Rat n 1 and mouse urinary protein, allergens of the
      fungus Alternaria alternata, and endotoxin. This article provides the essential
      context for subsequent reports that will describe the prevalence of allergens and
      endotoxin in U.S. households, their distribution by various housing
      characteristics, and their associations with allergic diseases such as asthma and
      rhinitis.

PMID- 12003759
TI  - Confirmation of uterotrophic activity of 3-(4-methylbenzylidine)camphor in the
      immature rat.
AB  - In this study we found that the ultraviolet sunscreen component 3-(4
      methylbenzylidine)camphor (4MBC) is uterotrophic in immature rats when
      administered by either subcutaneous injection or oral gavage. These data confirm
      earlier reports of uterotrophic activity for this agent when administered to
      immature rats in the diet or by whole-body immersion; however, they are in
      contrast to negative unpublished immature rat uterotrophic assay results. Data
      also indicate that 4MBC binds to isolated rat uterine estrogen receptors and
      shows activity in a human estrogen receptor yeast transactivation assay; however,
      we considered both of these effects equivocal. In this study, we confirmed the
      original observation that 4MBC was active as a mitogen to MCF-7 breast cancer
      cells. We evaluated and discounted the possibility that the estrogenic activity
      of 4MBC is related to its bulky camphor group, which is of similar molecular
      dimensions to that of the weak estrogen kepone. Uncertainty remains regarding the
      mechanism of the uterotrophic activity of 4MBC.

PMID- 12003760
TI  - Estimating the burden of disease from water, sanitation, and hygiene at a global
      level.
AB  - We estimated the disease burden from water, sanitation, and hygiene at the global
      level taking into account various disease outcomes, principally diarrheal
      diseases. The disability-adjusted life year (DALY) combines the burden from death
      and disability in a single index and permits the comparison of the burden from
      water, sanitation, and hygiene with the burden from other risk factors or
      diseases. We divided the world's population into typical exposure scenarios for
      14 geographical regions. We then matched these scenarios with relative risk
      information obtained mainly from intervention studies. We estimated the disease
      burden from water, sanitation, and hygiene to be 4.0% of all deaths and 5.7% of
      the total disease burden (in DALYs) occurring worldwide, taking into account
      diarrheal diseases, schistosomiasis, trachoma, ascariasis, trichuriasis, and
      hookworm disease. Because we based these estimates mainly on intervention
      studies, this burden is largely preventable. Other water- and sanitation-related
      diseases remain to be evaluated. This preliminary estimation of the global
      disease burden caused by water, sanitation, and hygiene provides a basic model
      that could be further refined for national or regional assessments. This
      significant and avoidable burden suggests that it should be a priority for public
      health policy.

PMID- 12003761
TI  - Indoor dampness and molds and development of adult-onset asthma: a population
      based incident case-control study.
AB  - Previous cross-sectional and prevalent case-control studies have suggested
      increased risk of asthma in adults related to dampness problems and molds in
      homes. We conducted a population-based incident case-control study to assess the
      effects of indoor dampness problems and molds at work and at home on development
      of asthma in adults. We recruited systematically all new cases of asthma during a
      2.5-year study period (1997-2000) and randomly selected controls from a source
      population consisting of adults 21-63 years old living in the Pirkanmaa Hospital
      district, South Finland. The clinically diagnosed case series consisted of 521
      adults with newly diagnosed asthma and the control series of 932 controls, after
      we excluded 76 (7.5%) controls with a history of asthma. In logistic regression
      analysis adjusting for confounders, the risk of asthma was related to the
      presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95%
      confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We
      estimated the fraction of asthma attributable to workplace mold exposure to be
      35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results
      provide new evidence of the relation between workplace exposure to indoor molds
      and adult-onset asthma.

PMID- 12003762
TI  - Children's exposure to chlorpyrifos and parathion in an agricultural community in
      central Washington State.
AB  - We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and
      parathion--in residences, and their metabolic by-products, in the urine of
      children 6 years old or younger in a central Washington State agricultural
      community. Exposures to two dimethyl OP pesticides (azinphos-methyl and phosmet)
      in this same population have been reported previously. We categorized children by
      parental occupation and by household proximity to pesticide-treated farmland.
      Median chlorpyrifos house dust concentrations were highest for the 49 applicator
      homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the
      14 nonagricultural reference homes (0.1 microg/g), and were statistically
      different (p < 0.001); we observed a similar pattern for parathion in house dust.
      Chlorpyrifos was measurable in the house dust of all homes, whereas we found
      parathion in only 41% of the homes. Twenty-four percent of the urine samples from
      study children had measurable 3,5,6-trichloro-2-pyridinol (TCPy) concentrations
      [limits of quantitation (LOQ) = 8 microg/L], and 7% had measurable 4-nitrophenol
      concentrations (LOQ = 9 microg/L). Child urinary metabolite concentrations did
      not differ across parental occupational classifications. Homes in close proximity
      (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01)
      and parathion (p = 0.014) house dust concentrations than did homes farther away,
      but this effect was not reflected in the urinary metabolite data. Use of OP
      pesticides in the garden was associated with an increase in TCPy concentrations
      in children's urine. Parathion concentrations in house dust decreased 10-fold
      from 1992 to 1995, consistent with the discontinued use of this product in the
      region in the early 1990s.

PMID- 12003763
TI  - Incorporating health and ecologic costs into agricultural production.

PMID- 12003764
TI  - Psychologic stress and asthma: neuropeptide involvement.

PMID- 12003765
TI  - Underground fires surface.

PMID- 12003766
TI  - High-resolution revolution.

PMID- 12003767
TI  - Would a rose not smell as sweet?

PMID- 12003768
TI  - Assessing assays.

PMID- 12003769
TI  - A cleaner way to color cotton.

PMID- 12003770
TI  - Ionic mechanisms and Ca(2+) regulation in airway smooth muscle contraction: do
      the data contradict dogma?
AB  - In general, excitation-contraction coupling in muscle is dependent on membrane
      depolarization and hyperpolarization to regulate the opening of voltage-dependent
      Ca(2+) channels and, thereby, influence intracellular Ca(2+) concentration
      ([Ca(2+)](i)). Thus Ca(2+) channel blockers and K(+) channel openers are
      important tools in the arsenals against hypertension, stroke, and myocardial
      infarction, etc. Airway smooth muscle (ASM) also exhibits robust Ca(2+), K(+),
      and Cl(-) currents, and there are elaborate signaling pathways that regulate
      them. It is easy, then, to presume that these also play a central role in
      contraction/relaxation of ASM. However, several lines of evidence speak to the
      contrary. Also, too many researchers in the ASM field view the sarcoplasmic
      reticulum as being centrally located and displacing its contents uniformly
      throughout the cell, and they have focused almost exclusively on the initial
      single [Ca(2+)] spike evoked by excitatory agonists. Several recent studies have
      revealed complex spatial and temporal heterogeneity in [Ca(2+)](i), the
      significance of which is only just beginning to be appreciated. In this review,
      we will compare what is known about ion channels in ASM with what is believed to
      be their roles in ASM physiology. Also, we will examine some novel ionic
      mechanisms in the context of Ca(2+) handling and excitation-contraction coupling
      in ASM.

PMID- 12003771
TI  - Proliferation of regulatory mechanisms for eNOS: an emerging role for the
      cytoskeleton.

PMID- 12003772
TI  - Microtubule-active agents modify nitric oxide production in pulmonary artery
      endothelial cells.
AB  - The effects of specific microtubule-active agents on nitric oxide (NO) production
      were examined in pulmonary artery endothelial cells (PAEC). PAEC were incubated
      with taxol, which stabilizes microtubules, or nocodazole, which disrupts
      microtubules, or both for 2-4 h. We then examined NO production, endothelial NO
      synthase (eNOS) activity, and eNOS association with heat shock protein (HSP) 90.
      Incubation of PAEC with taxol (15 microM) for 2-4 h resulted in an increase in NO
      production, eNOS activity, and the amount of HSP90 binding to eNOS. Incubation of
      PAEC with nocodazole (50 microM) for 2-4 h induced a decrease in NO production,
      eNOS activity, and the amount of HSP90 binding to eNOS. The presence of taxol in
      the culture medium prevented the effects of nocodazole on NO production and eNOS
      activity in PAEC. Geldanamycin, a HSP90 inhibitor, prevented the taxol-induced
      increase in eNOS activity. Taxol and nocodazole did not affect eNOS, HSP90, and
      tubulin protein contents in PAEC, as detected using Western blot analysis. These
      results indicate that the polymerization state of the microtubule cytoskeleton
      regulates NO production and eNOS activity in PAEC. The changes in eNOS activity
      induced by modification of microtubules are due, at least in part, to the altered
      binding of HSP90 to eNOS protein.

PMID- 12003773
TI  - System N in eNdothelium.

PMID- 12003774
TI  - Stereoselective transport of histidine in rat lung microvascular endothelial
      cells.
AB  - The transport characteristics of L- and D-histidine through the blood-lung
      barrier were studied in cultured rat lung microvascular endothelial cells
      (LMECs). L-Histidine uptake was a saturable process. The addition of metabolic
      inhibitors [2,4-dinitrophenol (DNP) and rotenone] reduced the uptake rate of L
      histidine. Ouabain, an inhibitor of Na(+)-K(+)-ATPase, also reduced uptake of L
      histidine. Moreover, the initial L-histidine uptake rate was reduced by the
      substitution of Na(+) with choline chloride and choline bicarbonate in the
      incubation buffer. The system N substrate, L-glutamic acid gamma-monohydroxamate,
      also inhibited uptake of L-histidine. However, system N-mediated transport was
      not pH sensitive. These results demonstrated that L-histidine is actively taken
      up by a system N transport mechanism into rat LMECs, with energy supplied by
      Na(+). Moreover, the Na(+)-independent system L substrate, 2-amino-2
      norbornanecarboxylic acid (BCH), had an inhibitory effect on L-histidine uptake
      in Na(+) removal, indicating facilitated diffusion by a Na(+)-independent system
      L transport into the rat LMECs. These results provide evidence for there being at
      least two pathways for L-histidine uptake into rat LMECs, a Na(+)-dependent
      system N and Na(+)-independent system L process. On the other hand, the uptake of
      D-histidine into rat LMECs was not reduced by the addition of DNP, rotenone, or
      ouabain, or by Na(+) replacement. Although the uptake of D-histidine was reduced
      in the presence of BCH, the addition of L-glutamic acid gamma-monohydroxamate did
      not significantly decrease uptake of D-histidine. These results suggest that the
      uptake of D-histidine by rat LMECs has different characteristics compared with
      its isomer, L-histidine, indicating that system N transport did not involve D
      histidine uptake.

PMID- 12003775
TI  - Parathyroid hormone-related protein response to hyperoxic lung injury.
AB  - Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar
      type II cells. Type II cell proliferation after lung injury from 85% oxygen is
      regulated, in part, by a fall in lung PTHrP. In this study, we investigated lung
      PTHrP after injury induced by >95% oxygen in rats and rabbits. In adult rats,
      lung PTHrP rose 10-fold over controls to 6,356 +/- 710 pg/ml (mean +/- SE) at 48
      h of hyperoxia. Levels fell to 299 +/- 78 pg/ml, and staining for PTHrP mRNA was
      greatly reduced at 60 h (P < 0.05), the point of most severe injury and greatest
      pneumocyte proliferation. In adult rabbits, lung PTHrP peaked at 3,289 +/- 230
      pg/ml after 64 h of hyperoxia with 24 h of normoxic recovery and then dropped to
      1,629 +/- 153 pg/ml at 48 h of recovery (P < 0.05). Type II cell proliferation
      peaked shortly after the fall in PTHrP. In newborn rabbits, lavage PTHrP
      increased by 50% during the first 8 days of hyperoxia, whereas type II cell
      growth decreased. PTHrP declined at the LD(50), concurrent with increased type II
      cell division. In summary, lung PTHrP initially rises after injury with >95%
      hyperoxia and then falls near the peak of injury. Changes in PTHrP are temporally
      related to type II cell proliferation and may regulate repair of lung injury.

PMID- 12003777
TI  - Cytokines and oxygen radicals after hyperoxia in preterm and term alveolar
      macrophages.
AB  - To determine if the alveolar macrophage inflammatory cytokine response to oxygen
      differs in premature cells, macrophages were obtained from litters of premature
      (27 days) and term (31 days) rabbits. The majority of these cells were
      nonspecific esterase positive and actively phagocytosed latex particles. The
      cells that expressed cytokines also reacted with a monoclonal antibody against
      rabbit macrophages. After incubation overnight in 5 or 95% oxygen, the amount of
      interleukin (IL)-1beta and IL-8 mRNA was assessed by RT-PCR and the amount of
      cytokine protein by quantitative immunofluorescence microscopy. The preterm
      macrophage showed a significant increase in cytokine mRNA and protein after
      overnight incubation in 95% oxygen. This response was not seen in the term cells.
      Only premature macrophages had a significant increase in intracellular oxygen
      radical content, measured by 2',7'-dichlorofluorescin analysis, after incubation
      in 95% oxygen. This enhanced inflammatory cytokine response to oxygen may be one
      mechanism involved in the early development of chronic lung disease in premature
      infants.

PMID- 12003776
TI  - Enalapril protects mice from pulmonary hypertension by inhibiting TNF-mediated
      activation of NF-kappaB and AP-1.
AB  - The present study was undertaken to investigate the effects of treatment with the
      angiotensin-converting enzyme (ACE) inhibitor enalapril in a mouse model of
      pulmonary hypertension induced by bleomycin. Bleomycin-induced lung injury in
      mice is mediated by enhanced tumor necrosis factor-alpha (TNF) expression in the
      lung, which determines the murine strain sensitivity to bleomycin, and murine
      strains are sensitive (C57BL/6) or resistant (BALB/c). Bleomycin induced
      significant pulmonary hypertension in C57BL/6, but not in BALB/c, mice; average
      pulmonary arterial pressure (PAP) was 26.4 +/- 2.5 mmHg (P < 0.05) vs. 15.2 +/- 3
      mmHg, respectively. Bleomycin treatment induced activation of nuclear factor (NF)
      kappaB and activator protein (AP)-1 and enhanced collagen and TNF mRNA expression
      in the lung of C57BL/6 but not in BALB/c mice. Double TNF receptor-deficient mice
      (in a C57BL/6 background) that do not activate NF-kappaB or AP-1 in response to
      bleomycin did not develop bleomycin-induced pulmonary hypertension (PAP 14 +/- 3
      mmHg). Treatment of C57BL/6 mice with enalapril significantly (P < 0.05)
      inhibited the development of pulmonary hypertension after bleomycin exposure.
      Enalapril treatment inhibited NF-kappaB and AP-1 activation, the enhanced TNF and
      collagen mRNA expression, and the deposition of collagen in bleomycin-exposed
      C57BL/6 mice. These results suggest that ACE inhibitor treatment decreases lung
      injury and the development of pulmonary hypertension in bleomycin-treated mice.

PMID- 12003778
TI  - Adhesion-dependent interactions between eosinophils and cholinergic nerves.
AB  - Eosinophils adhere to airway cholinergic nerves and influence nerve cell function
      by releasing granule proteins onto inhibitory neuronal M(2) muscarinic receptors.
      This study investigated the mechanism of eosinophil degranulation by cholinergic
      nerves. Eosinophils were cocultured with IMR32 cholinergic nerve cells, and
      eosinophil peroxidase (EPO) or leukotriene C(4) (LTC(4)) release was measured.
      Coculture of eosinophils with nerves significantly increased EPO and LTC(4)
      release compared with eosinophils alone. IMR32 cells, like parasympathetic
      nerves, express the adhesion molecules vascular cell adhesion molecule-1 and
      intercellular adhesion molecule-1 (ICAM-1). Inhibition of these adhesion
      molecules alone or in combination significantly inhibited eosinophil
      degranulation. IMR32 cells also significantly augmented the eosinophil
      degranulation produced by formyl-Met-Leu-Phe. Eosinophil adhesion to IMR32 cells
      resulted in an ICAM-1-mediated production of reactive oxygen species via a
      neuronal NADPH oxidase, inhibition of which significantly inhibited eosinophil
      degranulation. Additionally, eosinophil adhesion increased the release of ACh
      from IMR32 cells. These neuroinflammatory cell interactions may be relevant in a
      variety of inflammatory and neurological conditions.

PMID- 12003779
TI  - Pro-EMAP II is not primarily cleaved by caspase-3 and -7.
AB  - Endothelial monocyte-activating polypeptide (EMAP) II is a unique cytokine, also
      known as p43, the active mature form of which exhibits antiangiogenic properties
      in vivo and in vitro. The proteolytic enzymes associated with the cleavage and
      release of the active mature form, however, remain unclear. Here we show that, in
      contrast to prior observations, purified pro-EMAP II is not cleaved by either
      caspase-3 or -7 in vivo or in vitro. Thus other proteolytic processes, which
      allow it to induce apoptosis via caspase-3 activation in migrating and dividing
      endothelium, may be involved in the release of the active mature EMAP II.

PMID- 12003780
TI  - Role of resident alveolar macrophages in leukocyte traffic into the alveolar air
      space of intact mice.
AB  - Intratracheal instillation of the monocyte chemoattractant JE/monocyte
      chemoattractant protein (MCP)-1 in mice was recently shown to cause increased
      alveolar monocyte accumulation in the absence of lung inflammation, whereas
      combined JE/MCP-1/lipopolysaccharide (LPS) challenge provoked acute lung
      inflammation with early alveolar neutrophil and delayed alveolar monocyte influx.
      We evaluated the role of resident alveolar macrophages (rAM) in these leukocyte
      recruitment events and related phenomena of lung inflammation. Depletion of rAM
      by pretreatment of mice with liposomal clodronate did not affect the JE/MCP-1
      driven alveolar monocyte accumulation, despite the observation that rAM
      constitutively expressed the JE/MCP-1 receptor CCR2, as analyzed by flow
      cytometry and immunohistochemistry. In contrast, depletion of rAM largely
      suppressed alveolar cytokine release as well as neutrophil and monocyte
      recruitment profiles upon combined JE/MCP-1/LPS treatment. Despite this strongly
      attenuated alveolar inflammatory response, increased lung permeability was still
      observed in rAM-depleted mice undergoing JE/MCP-1/LPS challenge. Lung leakage was
      abrogated by codepletion of circulating neutrophils or administration of anti
      CD18. Collectively, rAM are not involved in JE/MCP-1-driven alveolar monocyte
      recruitment in noninflamed lungs but largely contribute to the alveolar cytokine
      response and enhanced early neutrophil and delayed monocyte influx under
      inflammatory conditions (JE/MCP-1/LPS deposition). Loss of lung barrier function
      observed under these conditions is rAM independent but involves circulating
      neutrophils via beta(2)-integrin engagement.

PMID- 12003781
TI  - Wild-type levels of the mouse Forkhead Box f1 gene are essential for lung repair.
AB  - The Forkhead Box (Fox) family of transcription factors plays important roles in
      regulating expression of genes involved in cellular proliferation and
      differentiation. In a previous study, we showed that newborn foxf1(+/-) mice with
      diminished Foxf1 levels exhibited abnormal formation of pulmonary alveoli and
      capillaries and died postnatally. Interestingly, surviving newborn foxf1(+/-)
      mice exhibited increased pulmonary Foxf1 levels and normal adult lung morphology,
      suggesting that wild-type Foxf1 levels are required for lung development and
      function. The present study was conducted to determine whether adult foxf1(+/-)
      mice were able to undergo lung repair similar to that observed in wild-type mice.
      We demonstrated that adult foxf1(+/-) mice died from severe lung hemorrhage after
      butylated hydroxytoluene (BHT) lung injury and that this phenotype was associated
      with a 10-fold decrease in pulmonary Foxf1 expression and increased alveolar
      endothelial cell apoptosis that disrupted capillary integrity. Furthermore, BHT
      induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic
      reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant
      protein B, platelet endothelial cell adhesion molecule, and vascular endothelial
      cadherin genes, whereas the expression of these genes was either transiently
      diminished or increased in wild-type lungs after BHT injury. Because these
      proteins are critical for lung morphogenesis and endothelial homeostasis, their
      decreased mRNA levels are likely contributing to BHT-induced lung hemorrhage in
      foxf1(+/-) mice. Collectively, our data suggest that sustained expression of
      Foxf1 is essential for normal lung repair and endothelial cell survival in
      response to pulmonary cell injury.

PMID- 12003782
TI  - Transgenic expression of protein phosphatase 2A regulatory subunit B56gamma
      disrupts distal lung differentiation.
AB  - The distal epithelium of the developing lung exhibits high-level expression of
      protein phosphatase 2A (PP2A), a vital signaling enzyme. Here we report the
      discovery that in the lung, the PP2A regulatory subunit B56gamma is expressed in
      a discrete developmental period, with the highest protein levels at embryonic day
      (e) 17, but no detectable protein in the newborn or adult. By in situ
      hybridization, B56gamma was highly expressed in the distal epithelium of newly
      forming airways and in mesenchymal cells. In contrast, expression of B56gamma was
      quite low in the bronchial epithelium and vascular smooth muscle. Transgenic
      expression of B56gamma using the lung-specific promoter for surfactant protein C
      (SP-C) resulted in neonatal death. Examination of lungs from SP-C-B56gamma
      transgenic e18 fetuses revealed proximal airways and normal blood vessels, but
      the tissue was densely populated with epithelial-type cells and was devoid of
      normal peripheral lung structure. A component of the Wnt signaling pathway, beta
      catenin, was developmentally regulated in the normal lung and was absent in lung
      tissue from B-56gamma transgenic fetuses. We propose that B56gamma is expressed
      at a particular stage of lung development to modulate PP2A action on the Wnt/beta
      catenin signaling pathway during lung airway morphogenesis.

PMID- 12003783
TI  - Inhibition of compensatory lung growth in endothelial nitric oxide synthase
      deficient mice.
AB  - Pneumonectomy results in rapid compensatory growth of the remaining lung and also
      leads to increased flow and shear stress, which are known to stimulate
      endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator
      of vascular endothelial growth factor-induced angiogenesis, which should
      necessarily occur during compensatory lung growth. Thus our hypothesis is that
      eNOS is critical for compensatory lung growth. To test this, left pneumonectomy
      was performed in eNOS-deficient mice (eNOS-/-), and compensatory growth of the
      right lung was characterized throughout 14 days postpneumonectomy and compared
      with wild-type pneumonectomy and sham controls. Compensatory lung growth was
      severely impaired in eNOS-/- mice, as demonstrated by significant reductions in
      lung weight index, lung volume index, and volume of respiratory region. Also,
      pneumonectomy-induced increases in alveolar surface density and cell
      proliferation were prevented in eNOS-/- mice, indicating that eNOS plays a role
      in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type
      mice treated with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine
      methyl ester. Together, these results indicate that eNOS is critical for
      compensatory lung growth.

PMID- 12003784
TI  - Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated
      eosinophil degranulation.
AB  - In vivo, eosinophils localize to airway cholinergic nerves in antigen-challenged
      animals, and inhibition of this localization prevents antigen-induced
      hyperreactivity. In this study, the mechanism of eosinophil localization to
      nerves was investigated by examining adhesion molecule expression by cholinergic
      nerves. Immunohistochemical and functional studies demonstrated that primary
      cultures of parasympathetic nerves express vascular cell adhesion molecule-1
      (VCAM-1) and after cytokine pretreatment with tumor necrosis factor-alpha and
      interferon-gamma intercellular adhesion molecule-1 (ICAM-1). Eosinophils adhere
      to these parasympathetic neurones after cytokine pretreatment via a CD11/18
      dependent pathway. Immunohistochemistry and Western blotting showed that a human
      cholinergic nerve cell line (IMR-32) expressed VCAM-1 and ICAM-1. Inhibitory
      experiments using monoclonal blocking antibodies to ICAM-1, VCAM-1, or CD11/18
      and with the very late antigen-4 peptide inhibitor ZD-7349 showed that
      eosinophils adhered to IMR-32 cells via these adhesion molecules. The protein
      kinase C signaling pathway is involved in this process as a specific inhibitor
      attenuated adhesion. Eosinophil adhesion to IMR-32 cells was associated with the
      release of eosinophil peroxidase and leukotriene C(4). Thus eosinophils adhere to
      cholinergic nerves via specific adhesion molecules, and this leads to eosinophil
      activation and degranulation; this may be part of the mechanism of eosinophil
      induced vagal hyperreactivity.

PMID- 12003785
TI  - Effects of diazepam and stress on lung inflammatory response in OVA-sensitized
      rats.
AB  - The influence of stress and diazepam treatment on airway inflammation was
      investigated in ovalbumin (OVA)-sensitized rats. Animals were injected with OVA
      plus aluminum hydroxide intraperitoneally (day 0) and boosted with OVA
      subcutaneously (day 7). From the first to 13th day after sensitization, rats were
      treated with diazepam, and 1 h later they were placed in a shuttle box where they
      received 50 mild escapable foot shocks/day preceded by a sound signal (S).
      Response during the warning (S) canceled shock delivery and terminated the S. On
      day 14, rats were submitted to a single session of 50 inescapable foot shocks
      preceded by S and then were challenged with OVA. High levels of stress were
      detected in shocked animals, manifested as ultrasonic vocalizations. Morphometric
      analysis of stressed animals revealed a significant increase in both edema and
      lymphomononucleated cells in airways compared with controls. Diazepam treatment
      reduced edema in stressed and nonstressed rats. No differences were found in
      polymorphonucleated cell infiltration. Diazepam treatment reduced
      lymphomononucleated cell infiltration in stressed animals. These data suggest
      that stress and diazepam treatment play relevant roles in edema and
      lymphomononucleated airway inflammation in OVA-sensitized rats.

PMID- 12003786
TI  - Role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway
      smooth muscle cells.
AB  - Airway remodeling, as manifested by an increase in airway smooth muscle mass,
      mucous gland hyperplasia, and subepithelial fibrosis, contributes to the airway
      hyperresponsiveness and fixed obstruction seen in some asthmatic patients. Here
      we investigated whether the Janus kinase-signal transducer and activator of
      transcription (JAK-STAT) pathway contributes to platelet-derived growth factor
      (PDGF)-stimulated mitogenesis of human airway smooth muscle cells (HASMC). PDGF
      treatment of quiescent HASMC resulted in the rapid tyrosine phosphorylation and
      DNA binding of STAT1 and STAT3. This phosphorylation was blocked by inhibition of
      Src and JAK2 kinases. In addition, STAT activation by PDGF was found to be redox
      dependent. Moreover, PDGF-induced thymidine uptake was completely blocked by
      pretreatment of HASMC with the STAT kinase inhibitors AG-490, SU-6656, and PP2.
      Interestingly, the JAK pathway was required for HASMC mitogenesis independently
      of mitogen-activated protein kinase activation. Inhibition of the Src and JAK
      kinases blocked PDGF-stimulated gene expression of the STAT target genes cyclin
      D1 and c-myc. These results indicate that the JAK-STAT pathway contributes to
      PDGF-induced mitogenesis, and thus this pathway may be important in the airway
      remodeling seen in some asthmatic patients.

PMID- 12003787
TI  - Src modulates serotonin-induced calcium signaling by regulating
      phosphatidylinositol 4,5-bisphosphate.
AB  - We tested the hypothesis that, in airway smooth muscle cells, stimulation of G
      protein-coupled receptors by contractile agonists activates Src kinase and that
      this kinase modulates cell contractility and Ca(2+) signaling by affecting the
      levels of the phospholipase C substrate phosphatidylinositol 4,5-bisphosphate
      (PIP(2)). Stimulation of cultured rat tracheal smooth muscle cells with serotonin
      (5-HT) induced an increase in Src activity, Ca(2+) mobilization, and contraction
      (decrease in cell area). 5-HT-evoked cell contraction was reduced by a specific
      inhibitor of Src family kinases, 4-amino-5(4-methylphenyl)-7-(t
      butyl)pyrazolo[3,4-d]pyrimidine (PP1). Peak Ca(2+) responses to 5-HT were
      attenuated by PP1 and an anti-Src-blocking antibody and augmented by expression
      of constitutively activated Y529F Src. Sustained phases of Ca(2+) responses to 5
      HT and Ca(2+) influx resulting from emptying of Ca(2+) stores in the endoplasmic
      reticulum by thapsigargin were also decreased after PP1 treatment. PP1
      significantly reduced the turnover of inositol phosphates produced on 5-HT
      stimulation and the amount of PIP(2) in the Triton X-100-insoluble lipid
      fraction. Overall, these data demonstrate that, in rat tracheal smooth muscle
      cells, Src kinase modulates 5-HT-evoked cell contractility and Ca(2+) signaling
      by regulating PIP(2) levels and Ca(2+) influx.

PMID- 12003788
TI  - Role of endothelin and endothelin A-type receptor in adaptation of the carotid
      body to chronic hypoxia.
AB  - Chronic exposure in a low-PO(2) environment (i.e., chronic hypoxia, CH) elicits
      an elevated hypoxic ventilatory response and increased hypoxic chemosensitivity
      in arterial chemoreceptors in the carotid body. In the present study, we examine
      the hypothesis that changes in chemosensitivity are mediated by endothelin (ET),
      a 21-amino-acid peptide, and ET(A) receptors, both of which are normally
      expressed by O(2)-sensitive type I cells. Immunocytochemical staining showed
      incremental increases in ET and ET(A) expression in type I cells after 3, 7, and
      14 days of CH (380 Torr). Peptide and receptor upregulation was confirmed in
      quantitative RT-PCR assays conducted after 14 days of CH. In vitro recordings of
      carotid sinus nerve activity after in vivo exposure to CH for 1-16 days
      demonstrated a time-dependent increase in chemoreceptor activity evoked by acute
      hypoxia. In normal carotid body, the specific ET(A) antagonist BQ-123 (5 microM)
      inhibited 11% of the nerve discharge elicited by hypoxia, and after 3 days of CH
      the drug diminished the hypoxia-evoked discharge by 20% (P < 0.01). This
      inhibitory effect progressed to 45% at day 9 of CH and to nearly 50% after 12,
      14, and 16 days of CH. Furthermore, in the presence of BQ-123, the magnitude of
      the activity evoked by hypoxia did not differ in normal vs. CH preparations,
      indicating that the increased activity was the result of endogenous ET acting on
      an increasing number of ET(A). Collectively, our data suggest that ET and ET(A)
      autoreceptors on O(2)-sensitive type I cells play a critical role in CH-induced
      increased chemosensitivity in the rat carotid body.

PMID- 12003789
TI  - Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in
      cardiomyocytes.
AB  - The p38 mitogen-activated protein kinase (MAPK) is phosphorylated in response to
      oxidative stress. Mitochondria in cardiomyocytes increase their generation of
      reactive oxygen species (ROS) during hypoxia (1-5% O(2)). These ROS participate
      in signal transduction pathways involved in adaptive responses, including
      ischemic preconditioning and gene transcription. The present study therefore
      tested the hypothesis that hypoxia induces p38 MAPK phosphorylation by augmenting
      mitochondrial ROS generation. In cardiomyocytes, phosphorylation of p38 was
      observed in a PO(2)-dependent manner during hypoxia. This response was inhibited
      by rotenone, thenoyltrifluoroacetone, and myxothiazol, inhibitors of
      mitochondrial complexes I, II, and III, respectively. A similar inhibition was
      observed in the cells pretreated with anion channel inhibitor DIDS, which may
      block ROS release from mitochondria. During normoxia, increases in mitochondrial
      ROS elicited by azide (1-2 mM) or by the mitochondrial inhibitor antimycin A
      caused increased phosphorylation of p38. Brief treatment with exogenous H(2)O(2)
      during normoxia also induced phosphorylation of p38 as hypoxia, but this effect
      was not abolished by myxothiazol or DIDS. The antioxidant N-acetyl-cysteine
      abolished the p38 response to hypoxia, presumably by scavenging H(2)O(2), but the
      mitogen extracellular receptor kinase inhibitor PD-98059 did not inhibit p38
      phosphorylation during hypoxia. Thus physiological hypoxia leads to p38
      phosphorylation through a mechanism that requires electron flux in the proximal
      region of the mitochondrial electron transport chain, which suggests that either
      H(2)O(2) or superoxide participates in activating that process.

PMID- 12003790
TI  - Histamine stimulates phosphorylation of adherens junction proteins and alters
      their link to vimentin.
AB  - Histamine increases microvascular permeability by creating small transitory (100
      400 nm) gaps between adjacent endothelial cells at sites of vascular endothelial
      (VE)-cadherin-based adhesion. We examined the effects of histamine on the
      proteins within the VE-cadherin-based adherens junction in primary human
      umbilical vein endothelial cells. VE-cadherin is linked not only by beta- and
      alpha-catenin to cortical actin but also by gamma-catenin to the intermediate
      filament vimentin. In mature human umbilical vein cultures, the VE-cadherin
      immunoprecipitate contained equivalent amounts of alpha- and beta-catenin, 130%
      as much beta- as gamma-catenin, and 50% as much actin as vimentin. Within 60 s,
      histamine decreased the fraction of VE-cadherin in the insoluble portion of the
      cell lysate by 35 +/- 1.5%. At the same time, histamine decreased the amount of
      vimentin that immunoprecipitated with VE-cadherin by 50 +/- 6%. Histamine did not
      affect the amount of actin or the amount of alpha-, beta-, or gamma-catenin that
      immunoprecipitated with VE-cadherin. Within 60 s, histamine simulated a doubling
      in the phosphorylation of VE-cadherin and beta- and gamma-catenin. The VE
      cadherin immunoprecipitate contained kinase activity that phosphorylated VE
      cadherin and gamma-catenin in vitro.

PMID- 12003791
TI  - Human bronchial epithelial cells express PAR-2 with different sensitivity to
      thermolysin.
AB  - Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in
      airway physiology. Proteases cleaving the extracellular NH(2) terminus of
      receptors activate or inactivate PAR, thus possessing a therapeutic potential.
      Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial
      cell lines human bronchial epithelial (HBE) and A549. Functional expression of
      PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease
      trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by
      the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2
      elicited Ca(2+) response in HBE and A549 cells depend on concentration and time
      of agonist superfusion. The response is partially pertussis toxin (PTX)
      insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished
      by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl
      borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited
      Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a
      dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines,
      thermolysin abolished the response to a subsequent trypsin challenge but not to
      SLIGKV. Thus different epithelial cell types express different PAR-2 with
      identical responses to physiological stimuli (trypsin, SLIGKV) but different
      sensitivity to modifying proteases, such as thermolysin.

PMID- 12003792
TI  - Bleomycin upregulates expression of gamma-glutamylcysteine synthetase in
      pulmonary artery endothelial cells.
AB  - The chemotherapeutic agent bleomycin induces pulmonary fibrosis through the
      generation of reactive oxygen species (ROS), which are thought to contribute to
      cellular damage and pulmonary injury. We hypothesized that bleomycin activates
      oxidative stress response pathways and regulates cellular glutathione (GSH).
      Bovine pulmonary artery endothelial cells exposed to bleomycin exhibit growth
      arrest and increased cellular GSH content. gamma-Glutamylcysteine synthetase
      (gamma-GCS) controls the key regulatory step in GSH synthesis, and Northern blots
      indicate that the gamma-GCS catalytic subunit [gamma-GCS heavy chain (gamma
      GCS(h))] is upregulated by bleomycin within 3 h. The promoter for human gamma
      GCS(h) contains consensus sites for nuclear factor-kappaB (NF-kappaB) and the
      antioxidant response element (ARE), both of which are activated in response to
      oxidative stress. Electrophoretic mobility shift assays show that bleomycin
      activates the transcription factor NF-kappaB as well as the ARE-binding factors
      Nrf-1 and -2. Nrf-1 and -2 activation by bleomycin is inhibited by the ROS
      quenching agent N-acetylcysteine (NAC), but not by U-0126, a MEK1/2 inhibitor
      that blocks bleomycin-induced MAPK activation. In contrast, NF-kappaB activation
      by bleomycin is inhibited by U-0126, but not by NAC. NAC and U-0126 both inhibit
      bleomycin-induced upregulation of gamma-GCS expression. These data suggest that
      bleomycin can activate oxidative stress response pathways and upregulate cellular
      GSH.

PMID- 12003793
TI  - Membrane currents in canine bronchial artery and their regulation by excitatory
      agonists.
AB  - The bronchial vasculature plays an important role in airway physiology and
      pathophysiology. We investigated the ion currents in canine bronchial smooth
      muscle cells using patch-clamp techniques. Sustained outward K(+) current evoked
      by step depolarizations was significantly inhibited by tetraethylamonium (1 and
      10 mM) or by charybdotoxin (10(-6) M) but was not significantly affected by 4
      aminopyridine (1 or 5 mM), suggesting that it was primarily a Ca(2+)-activated
      K(+) current. Consistent with this, the K(+) current was markedly increased by
      raising external Ca(2+) to 4 mM but was decreased by nifedipine (10(-6) M) or by
      removing external Ca(2+). When K(+) currents were blocked (by Cs(+) in the
      pipette), step depolarizations evoked transient inward currents with
      characteristics of L-type Ca(2+) current as follows: 1) activation that was
      voltage dependent (threshold and maximal at -50 and -10 mV, respectively); 2)
      inactivation that was time dependent and voltage dependent (voltage causing 50%
      maximal inactivation of -26 +/- 22 mV); and 3) blockade by nifedipine (10(-6) M).
      The thromboxane mimetic U-46619 (10(-6) M) caused a marked augmentation of
      outward K(+) current (as did 10 mM caffeine) lasting only 10-20 s; this was
      followed by significant suppression of the K(+) current lasting several minutes.
      Phenylephrine (10(-4) M) also suppressed the K(+) current to a similar degree but
      did not cause the initial transient augmentation. None of these three agonists
      elicited inward current of any kind. We conclude that bronchial arterial smooth
      muscle expresses Ca(2+)-dependent K(+) channels and voltage-dependent Ca(2+)
      channels and that its excitation does not involve activation of Cl(-) channels.

PMID- 12003794
TI  - Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation.
AB  - Chronic hypoxia (CH) augments endothelium-derived nitric oxide (NO)-dependent
      pulmonary vasodilation; however, responses to exogenous NO are reduced following
      CH in female rats. We hypothesized that CH-induced attenuation of NO-dependent
      pulmonary vasodilation is mediated by downregulation of vascular smooth muscle
      (VSM) soluble guanylyl cyclase (sGC) expression and/or activity, increased cGMP
      degradation by phosphodiesterase type 5 (PDE5), or decreased VSM sensitivity to
      cGMP. Experiments demonstrated attenuated vasodilatory responsiveness to the NO
      donors S-nitroso-N-acetylpenicillamine and spermine NONOate and to arterial
      boluses of dissolved NO solutions in isolated, saline-perfused lungs from CH vs.
      normoxic female rats. In additional experiments, the sGC inhibitor, 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, blocked vasodilation to NO donors in
      lungs from each group. However, CH was not associated with decreased pulmonary
      sGC expression or activity as assessed by Western blotting and cGMP
      radioimmunoassay, respectively. Consistent with our hypothesis, the selective
      PDE5 inhibitors dipyridamole and T-1032 augmented NO-dependent reactivity in
      lungs from CH rats, while having little effect in lungs from normoxic rats.
      However, the attenuated vasodilatory response to NO in CH lungs persisted after
      PDE5 inhibition. Furthermore, CH similarly inhibited vasodilatory responses to 8
      bromoguanosine 3'5'-cyclic monophosphate. We conclude that attenuated NO
      dependent pulmonary vasodilation after CH is not likely mediated by decreased sGC
      expression, but rather by increased cGMP degradation by PDE5 and decreased
      pulmonary VSM reactivity to cGMP.

PMID- 12003795
TI  - Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear
      leukocytes in the lung.
AB  - Phosphodiesterase (PDE) type 4 is the predominant PDE isozyme in
      polymorphonuclear leukocytes (PMN) and plays a key role in the regulation of PMN
      activation. The aim of this study was to examine the effect of a PDE type 4
      inhibitor, rolipram, on the functional changes and the retention of PMN in the
      lung. In vitro, F-actin content and L-selectin and CD11b expression of PMN
      stimulated by N-formyl-Met-Leu-Phe were measured by flow cytometry. PMN
      deformability was evaluated using silicon microchannels. Rolipram reduced the
      increase of F-actin and CD11b but did not change the decrease of L-selectin.
      Rolipram inhibited the increase of the transit time of PMN through the
      microchannel. We evaluated the retention of PMN in the lung in vivo by infusing
      labeled blood into the vena cava and examining the recovery into aortic root
      samples in rabbits. Rolipram inhibited the retention of stimulated PMN in the
      lung. In conclusion, a PDE type 4 inhibitor, rolipram, reduces the retention of
      PMN in the lung by reducing deformability change and CD11b upregulation of PMN.

PMID- 12003796
TI  - Composition, biophysical properties, and morphometry of plasma membranes in
      pulmonary interstitial edema.
AB  - We evaluated the changes in plasma membrane composition, biophysical properties,
      and morphology of pulmonary endothelial cells in anesthetized rabbits receiving
      0.5 ml. kg(-1). min(-1) saline infusion for 180 min, causing mild interstitial
      edema. Plasma membrane fractions were obtained from lung homogenates with
      gradient centrifugation, allowing a sixfold enrichment in caveolin-1. In
      edematous lungs, cholesterol content and phospholipidic phosphorus increased by
      15 and 40%, respectively. These data correlated with morphometric analysis of
      lungs fixed in situ by vascular perfusion with 2.5% glutaraldehyde, suggesting a
      relative increase in surface of luminal to interstitial front of the capillary
      endothelial cells, due to a convoluted luminal profile. In edematous lungs, the
      fraction of double-bound fatty acids increased in membrane lipids; moreover, the
      phosphatidylcholine/phosphatidylethanolamine and the cholesterol/phospholipid
      ratios decreased. These changes were consistent with the increase in fluorescence
      anisotropy of plasma membrane, indicating an increase in its fluidity. Data
      suggest that mechanical stimuli elicited by a modest (approximately 4%) increase
      in extravascular water cause marked changes in plasma membranes that may be of
      relevance in signal transduction and endothelial cell activation.

PMID- 12003797
TI  - Prologue: nonclassical modalities of myocardial preconditioning.

PMID- 12003798
TI  - Role of delta-opioid receptor agonists on infarct size reduction in swine.
AB  - Opioids are involved in cardiac ischemic preconditioning. Important species
      differences in cellular signaling mechanisms, antiarrhythmic, and antistunning
      effects have been described. The role of the delta-opioid receptor activation in
      swine remains unknown. Forty minutes before a 45-min occlusion and 180-min
      reperfusion of the left anterior descending coronary artery, open-chest,
      pentobarbital-anesthetized swine received either 1) saline (controls); 2) [D
      Ala(2),D-Leu(5)]enkephalin (DADLE); 3) [D-Pen(2,5)]enkephalin (DPDPE); 4)
      deltorphin-D, a novel delta(2)-opioid agonist; or 5) ischemic preconditioning
      (IP). Assessed were 1) infarct size to area at risk (IS, triphenyltetrazolium
      staining), 2) regional and global myocardial function (sonomicrometry,
      ventricular pressure catheters), and 3) arrhythmias (electrocardiogram analyses).
      It was found that DPDPE and deltorphin-D pretreatment reduced IS from 64.7 +/- 5
      to 36.5 +/- 6% and 27.4 +/- 11% (P < 0.01), respectively, whereas DADLE had no
      effect (66.8 +/- 3%). Both IP and DADLE had a proarrhythmic effect (P < 0.01).
      However, no differences in global or regional myocardial function or arrhythmia
      scores were observed between groups. This suggests that delta-receptor-specific
      opioids provide cardioprotection in swine.

PMID- 12003799
TI  - Cardiac preconditioning with 4-h, 17 degrees C ischemia reduces [Ca(2+)](i) load
      and damage in part via K(ATP) channel opening.
AB  - Brief ischemia before normothermic ischemia protects hearts against reperfusion
      injury (ischemic preconditioning, IPC), but it is unclear whether it protects
      against long-term moderate hypothermic ischemia. We explored in isolated guinea
      pig hearts 1) the influence of two 2-min periods of normothermic ischemia before
      4 h, 17 degrees C hypothermic ischemia on cardiac cytosolic [Ca(2+)], mechanical
      and metabolic function, and infarct size, and 2) the potential role of K(ATP)
      channels in eliciting cardioprotection. We found that IPC before 4 h moderate
      hypothermia improved myocardial perfusion, contractility, and relaxation during
      normothermic reperfusion. Protection was associated with markedly reduced
      diastolic [Ca(2+)] loading throughout both hypothermic storage and reperfusion.
      Global infarct size was markedly reduced from 36 +/- 2 (SE)% to 15 +/- 1% with
      IPC. Bracketing ischemic pulses with 200 microM 5-hydroxydecanoic acid or 10
      microM glibenclamide increased infarct size to 28 +/- 3% and 26 +/- 4%,
      respectively. These results suggest that brief ischemia before long-term
      hypothermic storage adds to the cardioprotective effects of hypothermia and that
      this is associated with decreased cytosolic [Ca(2+)] loading and enhanced ATP
      sensitive K channel opening.

PMID- 12003800
TI  - Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild
      type and PKC epsilon knockout mouse hearts.
AB  - Sphingosine-1-phosphate (S1P) protects neonatal rat cardiac myocytes from hypoxic
      damage through unknown signaling pathways. We tested the hypothesis that S1P
      induced cardioprotection requires activation by the epsilon-isoform of protein
      kinase C (PKC epsilon) by subjecting hearts isolated from PKC epsilon knockout
      mice and wild-type mice to 20 min of global ischemia and 30 min of reperfusion.
      Pretreatment with a 2-min infusion of 10 nM S1P improved recovery of left
      ventricular developed pressure (LVDP) in both wild-type and PKC epsilon knockout
      hearts and reduced the rise in LV end-diastolic pressure (LVEDP) and creatine
      kinase (CK) release. Pretreatment for 2 min with 10 nM of the ganglioside GM-1
      also improved recovery of LVDP and suppressed CK release in wild-type hearts but
      not in PKC epsilon knockout hearts. Importantly, GM-1 but not S1P, increased the
      proportion of PKC epsilon localized to particulate fractions. Our results suggest
      that GM-1, which enhances endogenous S1P production, reduces cardiac injury
      through PKC epsilon-dependent intracellular pathways. In contrast, extracellular
      S1P induces equivalent cardioprotection through PKC epsilon-independent signaling
      pathways.

PMID- 12003801
TI  - Cardioprotective effect of ischemic preconditioning is preserved in food
      restricted senescent rats.
AB  - Ischemic preconditioning (PC) has been proposed as an endogenous form of
      protection against-ischemia reperfusion injury. We have shown that PC does not
      prevent postischemic dysfunction in the aging heart. This phenomenon could be due
      to the reduction of cardiac norepinephrine release, and it has also been
      previously demonstrated that age-related decrease of norepinephrine release from
      cardiac adrenergic nerves may be restored by caloric restriction. We investigated
      the effects on mechanical parameters of PC against 20 min of global ischemia
      followed by 40 min of reperfusion in isolated hearts from adult (6 mo) and "ad
      libitum"-fed and food-restricted senescent (24 mo) rats. Norepinephrine release
      in coronary effluent was determined by high-performance liquid chromatography.
      Final recovery of percent developed pressure was significantly improved after PC
      in adult hearts versus unconditioned controls (85.2 +/- 19% vs. 51.5 +/- 10%, P <
      0.01). The effect of PC on developed pressure recovery was absent in ad libitum
      fed rats, but it was restored in food-restricted senescent hearts (66.6 +/- 13%
      vs. 38.3 +/- 11%, P < 0.05). Accordingly, norepinephrine release significantly
      increased after PC in both adult and in food-restricted senescent hearts, and
      depletion of myocardial norepinephrine stores by reserpine abolished the PC
      effect in both adult and in food-restricted senescent hearts. We conclude that PC
      reduces postischemic dysfunction in the hearts from adult and food-restricted but
      not in ad libitum-fed senescent rats. Despite the possibility of multiple age
      related mechanisms, the protection afforded by PC was correlated with increased
      norepinephrine release, and it was blocked by reserpine in both adult and food
      restricted senescent hearts. Thus caloric restriction may restore PC in the aging
      heart probably via increased norepinephrine release.

PMID- 12003802
TI  - Pharmacological preconditioning with resveratrol: role of nitric oxide.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene), a recently described grape-derived
      polyphenolic antioxidant, has been found to protect the heart from ischemic
      reperfusion injury. The present study sought to determine the mechanism of
      cardioprotection by investigating the ability of resveratrol to precondition the
      heart. Isolated perfused rat hearts were randomly divided into six groups: group
      I was perfused for 15 min with Kreb-Henseleit buffer (KHB) only; group II was
      perfused with 10 microM resveratrol; group III was perfused with 10 microM
      resveratrol plus 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME), a
      nonselective nitric oxide (NO) synthase (NOS) inhibitor; group IV was perfused
      with 10 microM resveratrol plus 100 microM aminoguanidine (AG), an inducible NOS
      (iNOS) blocker; and groups V and VI consisted of hearts perfused with L-NAME and
      AG, respectively. The perfusion was then switched to working mode, and all hearts
      were made globally ischemic for 30 min followed by 2 h of reperfusion.
      Preconditioning of the hearts with resveratrol provided cardioprotection as
      evidenced by improved postischemic ventricular functional recovery (developed
      pressure and aortic flow) and reduced myocardial infarct size and cardiomyocyte
      apoptosis. Resveratrol-mediated cardioprotection was completely abolished by both
      L-NAME and AG. In a separate study, hearts were examined for iNOS mRNA induction.
      Resveratrol caused an induction of the expression of iNOS mRNA beginning at 30
      min after reperfusion, increasing steadily up to 60 min of reperfusion, and then
      decreasing progressively up to 2 h after reperfusion. Preperfusion of the hearts
      with AG almost completely blocked the induction of iNOS. The results of our study
      demonstrate that resveratrol can pharmacologically precondition the heart in a NO
      dependent manner.

PMID- 12003803
TI  - Pharmacological preconditioning with resveratrol: an insight with iNOS knockout
      mice.
AB  - Resveratrol, a natural antioxidant and polyphenol found in grapes and wine, has
      been found to pharmacologically precondition the heart through the upregulation
      of nitric oxide (NO). To gain further insight of the role of NO in resveratrol
      preconditioning, mouse hearts devoid of any copies of inhibitory NO synthase
      (iNOS) (iNOS knockout) and corresponding wild-type hearts were perfused with 10
      microM resveratrol for 15 min followed by 25 min of ischemia and 2 h of
      reperfusion. Control experiments were performed with wild-type and iNOS knockout
      hearts that were not treated with resveratrol. Resveratrol-treated wild-type
      mouse hearts displayed significant improvement in postischemic ventricular
      functional recovery compared with those of nontreated hearts. Both resveratrol
      treated and nontreated iNOS knockout mouse hearts resulted in relatively poor
      recovery in ventricular function compared with wild-type resveratrol-treated
      hearts. Myocardial infarct size was lower in the resveratrol-treated wild-type
      mouse hearts compared with other group of hearts. In concert, a number of
      apoptotic cardiomyocytes was lower in the wild-type mouse hearts treated with
      resveratrol. Cardioprotective effects of resveratrol was abolished when the wild
      type mouse hearts were simultaneously perfused with aminoguanidine, an iNOS
      inhibitor. Resveratrol induced the expression of iNOS in the wild-type mouse
      hearts, but not in the iNOS knockout hearts, after only 30 min of reperfusion.
      Expression of iNOS remained high even after 2 h of reperfusion. Resveratrol
      treated wild-type mouse hearts were subjected to a lower amount of oxidative
      stress as evidenced by reduced amount of malonaldehyde content in these hearts
      compared with iNOS knockout and untreated hearts. The results of this study
      demonstrated that resveratrol was unable to precondition iNOS knockout mouse
      hearts, whereas it could successfully precondition the wild-type mouse hearts,
      indicating an essential role of iNOS in resveratrol preconditioning of the heart.

PMID- 12003804
TI  - Protease-activated receptor-2 activation improves efficiency of experimental
      ischemic preconditioning.
AB  - Protease-activated receptor-2 (PAR-2) is a member of seven transmembrane domain G
      protein-coupled receptors activated by proteolytic cleavage. PAR-2 is involved in
      inflammatory events and cardiac ischemic reperfusion injury. The objective of
      this study was to investigate the effects of PAR-2 in experimental myocardial
      ischemic preconditioning. To monitor the effects of PAR-2, Langendorff-perfused
      rat hearts were used. These hearts were treated with PAR-2-activating peptide
      (PAR-2AP) in various protocols. Hemodynamic parameters (left ventricular
      developed pressure, left ventricular diastolic pressure, coronary flow rate, and
      heart rate), several indexes of oxidative injury, and neutrophil accumulation
      were evaluated. We show for the first time that enhanced PAR-2 activation
      improves efficiency of ischemic preconditioning and reduces cardiac inflammation
      in the rat heart. Indeed, after PAR-2AP infusion we found that hemodynamic
      parameters, oxidative injury, infarct size, and neutrophil accumulation were
      involved. These data support the concept that PAR-2-dependent cell trafficking
      may regulate signaling responses to cardiac ischemia and inflammation.

PMID- 12003805
TI  - Attenuation of heat shock-induced cardioprotection by treatment with the opiate
      receptor antagonist naloxone.
AB  - Whole body hyperthermia induces heat shock proteins (HSPs), which confer
      cardioprotection. Several opioid receptor subtypes are expressed in the heart and
      are linked to cardioprotection; however, no one has attempted to link the
      protection elicited by heat stress (HS) to opioids. Therefore, we investigated
      the effect of an opiate receptor antagonist, naloxone, on HS-induced
      cardioprotection. Anesthetized Sprague-Dawley rats were subjected to HS (42
      degrees C for 20 min) with and without naloxone pretreatment and were allowed to
      recover for 48 h. They then underwent 30 min of ischemia followed by 2 h of
      reperfusion. An acute HS group was given an intravenous bolus of naloxone (3
      mg/kg) 10 min before index ischemia. Infarct size (IS), expressed as a percentage
      of the area at risk (IS/AAR), was determined. The right heart was excised for
      analysis of HSP content by Western blot. Heat-shocked rats showed significant
      reductions in IS/AAR versus control (16 +/- 3 vs. 58 +/- 4%, P < 0.001).
      Pretreatment with naloxone before HS attenuated the protective effects in a dose
      dependent fashion, with significant attenuation of protection occurring at 15
      mg/kg naloxone versus heat shock (42 +/- 6 vs. 16 +/- 3%, P < 0.001). Acute
      treatment with naloxone (3 mg/kg) 48 h after recovery from HS also significantly
      attenuated the delayed protective effect (47 +/- 4 vs. 16 +/- 3%, P < 0.001). No
      difference was seen in the level of HSP70 induced in the different groups. We
      conclude that heat shock-induced cardioprotection can be attenuated by naloxone,
      an opiate receptor antagonist, without reducing the levels of certain HSPs. These
      results suggest there may be a link between the endogenous release of opioids and
      HS that mediates cardioprotection.

PMID- 12003806
TI  - Isoflurane-induced preconditioning is attenuated by diabetes.
AB  - Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of
      mitochondrial ATP-regulated K(+) channels. We tested the hypothesis that diabetes
      mellitus interferes with isoflurane-induced preconditioning. Acutely
      instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0,
      0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence
      of diabetes (3 wk after administration of alloxan and streptozotocin) in six
      experimental groups. All dogs were subjected to a 60-min left anterior descending
      coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size
      (triphenyltetrazolium staining) was 29 +/- 3% (n = 8) of the left ventricular
      area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2
      and 13 +/- 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs,
      respectively). Diabetes alone did not alter infarct size (30 +/- 3%; n = 8) but
      blocked the protective effects of 0.32% (27 +/- 2%; n = 7) and not 0.64%
      isoflurane (18 +/- 3%; n = 7). Infarct size was directly related to blood glucose
      concentrations in diabetic dogs, but this relationship was abolished by higher
      concentrations of isoflurane. The results indicate that blood glucose and end
      tidal isoflurane concentrations are important determinants of infarct size during
      anesthetic-induced preconditioning.

PMID- 12003807
TI  - Block of the background K(+) channel TASK-1 contributes to arrhythmogenic effects
      of platelet-activating factor.
AB  - Platelet-activating factor (PAF), an inflammatory phospholipid, induces
      ventricular arrhythmia via an unknown ionic mechanism. We can now link PAF
      mediated cardiac electrophysiological effects to inhibition of a two-pore domain
      K(+) channel [TWIK-related acid-sensitive K(+) background channel (TASK-1)].
      Superfusion of carbamyl-PAF (C-PAF), a stable analog of PAF, over murine
      ventricular myocytes causes abnormal automaticity, plateau phase arrest of the
      action potential, and early afterdepolarizations in paced and quiescent cells
      from wild-type but not PAF receptor knockout mice. C-PAF-dependent currents are
      insensitive to Cs(+) and are outwardly rectifying with biophysical properties
      consistent with a K(+)-selective channel. The current is blocked by TASK-1
      inhibitors, including protons, Ba(2+), Zn(2+), and methanandamide, a stable
      analog of the endogenous lipid ligand of cannabinoid receptors. In addition, when
      TASK-1 is expressed in CHO cells that express an endogenous PAF receptor,
      superfusion of C-PAF decreases the expressed current. Like C-PAF, methanandamide
      evoked spontaneous activity in quiescent myocytes. C-PAF- and methanandamide
      sensitive currents are blocked by a specific protein kinase C (PKC) inhibitor,
      implying overlapping signaling pathways. In conclusion, C-PAF blocks TASK-1 or a
      closely related channel, the effect is PKC dependent, and the inhibition alters
      the electrical activity of myocytes in ways that would be arrhythmogenic in the
      intact heart.

PMID- 12003808
TI  - A 4-AP-sensitive current is enhanced by chronic carbon monoxide exposure in
      coronary artery myocytes.
AB  - A physiological role of carbon monoxide has been suggested for coronary myocytes;
      however, direct evidence is lacking. The objective of this study was to test the
      effect of chronic carbon monoxide exposure on the K(+) currents of the coronary
      myocytes. The effect of 3-wk chronic exposure to carbon monoxide was assessed on
      K(+) currents in isolated rat left coronary myocytes by the use of the patch
      clamp technique in the whole cell configuration. Moreover, membrane potential
      studies were performed on coronary artery rings using intracellular
      microelectrodes, and coronary blood flow in isolated heart preparation was
      recorded. Carbon monoxide did not change the amplitude of global whole cell K(+)
      current, but it did increase the component sensitive to 1 mM 4-aminopyridine.
      Carbon monoxide exposure hyperpolarized coronary artery segments by approximately
      10 mV and, therefore, increased their sensitivity to 4-aminopyridine. This effect
      was associated with an enhancement of coronary blood flow. We conclude that
      chronic carbon monoxide increases a 4-aminopyridine-sensitive current in isolated
      coronary myocytes. This mechanism could, in part, contribute to hyperpolarization
      and to increased coronary blood flow observed with carbon monoxide.

PMID- 12003809
TI  - Microinjection of ANG II into paraventricular nucleus enhances cardiac
      sympathetic afferent reflex in rats.
AB  - The aims of present study were to determine whether angiotensin II (ANG II) in
      the paraventricular nucleus (PVN) is involved in the central integration of the
      cardiac sympathetic afferent reflex and whether this effect is mediated by the
      ANG type 1 (AT(1)) receptor. While the animals were under alpha-chloralose and
      urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic
      nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical
      vagotomized rats. A cannula was inserted into the left PVN for microinjection of
      ANG II. The cardiac sympathetic afferent reflex was tested by electrical
      stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac
      sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4
      microg in 2 microl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the
      PVN resulted in dose-related increases in the RSNA responses to electrical
      stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation
      increased significantly at the highest dose of ANG II (3 nmol). The effects of
      ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN.
      Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA
      responses to epicardial application of BK, which was abolished by pretreatment
      with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II
      in the PVN augments the cardiac sympathetic afferent reflex evoked by both
      electrical stimulation of cardiac sympathetic afferent nerves and epicardial
      application of BK. These central effects of ANG II are mediated by AT(1)
      receptors.

PMID- 12003810
TI  - Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G
      protein dependent and independent.
AB  - The endogenous cannabinoid anandamide (arachidonylethanolamide) produces
      vasorelaxation in different vascular beds. In the present study, we found that
      anandamide and a metabolically stable analog, methanandamide, produced dose
      dependent (10 nM-10 microM) vasorelaxation of approximately 80% in a rabbit
      aortic ring preparation in an endothelium-dependent manner. Non-endothelium
      dependent vasorelaxation was observed to be a maximum of 20-22% at >10 microM
      methanandamide. The efficacious CB(1) receptor analogs desacetyllevonantradol (10
      microM) and WIN55212-2 (10 microM) failed to produce vasorelaxation; however, the
      endothelium-dependent vasorelaxation evoked by methanandamide was partially (75%)
      blocked by the CB(1) receptor antagonist SR141716A. The VR(1) vanilloid receptor
      antagonist capsazepine or the calcitonin gene-related peptide (CGRP) antagonist
      CGRP-(8-37) partially attenuated (25%) the vasorelaxation in endothelium-intact
      preparations and greatly reduced the response in endothelium-denuded
      preparations. Pretreatment of aortic rings with N(G)-nitro-L-arginine methyl
      ester completely blocked the methanandamide-, capsaicin-, and CGRP-induced
      vasorelaxation. Pretreatment of aortic rings with pertussis toxin attenuated the
      methanandamide-induced vasorelaxation in endothelium-intact aortic rings,
      indicating the involvement of G(i/o) proteins in the vasorelaxation; however,
      pertussis toxin treatment failed to block the endothelium-independent response.
      Thus, in the rabbit aorta, methanandamide-induced vasorelaxation exhibits two
      components: 1) in endothelium-intact rings, an SR141716A-sensitive, non-CB(1)
      receptor component that requires pertussis toxin-sensitive G proteins and nitric
      oxide (NO) production; and 2) in endothelium-denuded rings, a component that is
      mediated by VR(1) vanilloid receptors and possibly by the subsequent release of
      CGRP that requires NO production but is independent of pertussis toxin-sensitive
      G proteins.

PMID- 12003811
TI  - Heme oxygenase activity in placenta: direct dependence on oxygen availability.
AB  - Carbon monoxide (CO), which is formed endogenously from heme catalyzed by heme
      oxygenase (HO), is proposed to play a role in vascular control. The mRNA and
      protein expression of the inducible isoform of HO (HO-1) increases in response to
      hypoxia, and it has been assumed that HO activity also increases. This assumption
      requires evaluation because the catalytic activity of HO requires three molecules
      of O(2) for each molecule of CO formed from heme, and HO activity may be limited
      by O(2) availability. To test the hypothesis that low physiological O(2)
      concentrations limit HO activity, heme-derived CO formation by microsomal
      fractions of homogenates of chorionic villi of human placentas was determined
      after exposure to 0, 1, 5, or 21% O(2). Results revealed that HO activity was
      directly dependent on O(2) concentration. Thus, although hypoxia may increase HO
      protein and mRNA expression, there is a progressive decrease in HO activity with
      decreasing O(2) concentration and the dependence of HO activity on O(2)
      concentration is similar in chorionic villi from noninfarcted areas of
      preeclamptic and normotensive placenta.

PMID- 12003812
TI  - Impaired endothelium-mediated relaxation in isolated cerebral arteries from
      insulin-resistant rats.
AB  - Insulin resistance (IR) impairs vascular responses in peripheral arteries.
      However, the effects of IR on cerebrovascular control mechanisms are completely
      unexplored. We examined the vascular function of isolated middle cerebral
      arteries (MCAs) from fructose-fed IR and control rats. Endothelium-dependent
      vasodilation elicited by bradykinin (BK) was reduced in IR compared with control
      MCAs. Maximal dilation to BK (10(-6) M) was 38 +/- 3% (n = 13) in control and 19
      +/- 3% (n = 10) in IR arteries (P < 0.01). N(omega)-nitro-L-arginine methyl ester
      (L-NAME; 10 microM) decreased responses to BK in control arteries by
      approximately 65% and inhibited the already reduced responses completely in IR
      MCAs. Indomethacin (10 microM) reduced relaxation to BK in control MCAs by
      approximately 40% but was largely ineffective in IR arteries. Combined L-NAME and
      indomethacin treatments eliminated the BK-induced dilation in both groups.
      Similarly to BK, endothelium-mediated and mainly cyclooxygenase (COX)-dependent
      dilation to calcium ionophore A23187 was reduced in IR arteries compared with
      controls. In contrast, vascular relaxation to sodium nitroprusside was similar
      between the IR and control groups. These findings demonstrate that endothelium
      dependent dilation in cerebral arteries is impaired in IR primarily because of a
      defect of the COX-mediated pathways. In contrast, nitric oxide-mediated dilation
      remains intact in IR arteries.

PMID- 12003813
TI  - Endothelial nitric oxide production during in vitro simulation of external limb
      compression.
AB  - External pneumatic compression (EPC) is effective in preventing deep vein
      thrombosis (DVT) and is thought to alter endothelial thromboresistant properties.
      We investigated the effect of EPC on changes in nitric oxide (NO), a critical
      mediator in the regulation of vasomotor and platelet function. An in vitro cell
      culture system was developed to simulate flow and vessel collapse conditions
      under EPC. Human umbilical vein endothelial cells were cultured and subjected to
      tube compression (C), pulsatile flow (F), or a combination of the two (FC). NO
      production and endothelial nitric oxide synthase (eNOS) mRNA expression were
      measured. The data demonstrate that in the F and FC groups, there is a rapid
      release of NO followed by a sustained increase. NO production levels in the F and
      FC groups were almost identical, whereas the C group produced the same low amount
      of NO as the control group. Conditions F and FC also upregulate eNOS mRNA
      expression by a factor of 2.08 +/- 0.25 and 2.11 +/- 0.21, respectively, at 6 h.
      Experiments with different modes of EPC show that NO production and eNOS mRNA
      expression respond to different time cycles of compression. These results
      implicate enhanced NO release as a potentially important factor in the prevention
      of DVT.

PMID- 12003814
TI  - Strain-specific patterns of autonomic nervous system activity and heart failure
      susceptibility in mice.
AB  - Transgenic mice are widely used to study cardiac function, but strain-dependent
      differences in autonomic nervous system activity (ANSA) have not been explored.
      We compared 1) short-term pharmacological responses of cardiac rhythm in FVB vs.
      C57Black6/SV129 wild-type mice and 2) long-term physiological dynamics of cardiac
      rhythm and survival in tumor necrosis factor (TNF)-alpha transgenic mice with
      heart failure (TNF-alpha mice) on defined backgrounds. Ambulatory telemetry
      electrocardiographic recordings and response to saline, adrenergic, and
      cholinergic agents were examined in FVB and C57Black6/SV129 mice. In FVB mice,
      baseline heart rate (HR) was higher and did not change after injection of
      isoproterenol or atropine but decreased with propranolol. In C57Black6/SV129
      mice, HR did not change with propranolol but increased with isoproterenol or
      atropine. Mean HR, but not indexes of HR variability, was an excellent predictor
      of response to autonomic agents. The proportion of surviving animals was higher
      in TNF-alpha mice on an FVB background than on a mixed FVB/C57Black6 background.
      The homeostatic states of ANSA are strain specific, which can explain the
      interstrain differences in mean HR, pharmacological responses, and survival of
      animals with congestive heart failure. Strain-specific differences should be
      considered in selecting the strains of mice used for transgenic and gene
      targeting experiments.

PMID- 12003815
TI  - Phosphorylation of eNOS initiates excessive NO production in early phases of
      portal hypertension.
AB  - Akt, also known as protein kinase B, is a serine/threonine kinase. Akt becomes
      active when phosphorylated by the activation of receptor tyrosine kinases, G
      protein-coupled receptors, and mechanical forces such as shear stress. Studies in
      vitro have shown that Akt can directly phosphorylate endothelial nitric oxide
      (NO) synthase (eNOS) and activate the enzyme, leading to NO production. The aim
      of this study was to test the hypothesis that the phosphorylation of eNOS plays a
      role in the enhanced NO production observed in early portal hypertension. Male
      Sprague-Dawley rats were subjected to either sham or portal vein ligation (PVL),
      and mesenteric arterial beds were used for ex vivo perfusion studies. Mesenteric
      arterial beds from PVL rats had an approximately 60-70% decrease in response to
      methoxamine (an alpha(1)-agonist and vasoconstrictor) compared with the sham
      group (P < 0.01). When N(G)-monomethyl-L-arginine (a NOS inhibitor) was added to
      the perfusion, the difference in perfusion pressure between the two groups was
      abolished, suggesting that enhanced NO production in the PVL group blunted the
      response to the vasoconstrictor. The reduced responsiveness in PVL was not due to
      changes in eNOS expression but was due to an increase in enzyme-specific
      activity, suggesting posttranslational modification of eNOS. The phosphorylation
      of eNOS at Ser(1176) was significantly increased by twofold (P < 0.05) in the PVL
      group. Furthermore, PVL significantly increased Akt phosphorylation (an active
      form of Akt) by threefold (P < 0.05). When vessels were treated with wortmannin
      (10 nM) to block the phosphatidylinositol-3-OH-kinase/Akt pathway, NO-induced
      vasodilatation was significantly reduced. These results suggest that the
      phosphorylation of eNOS by Akt activates the enzyme and may be the first step
      leading to an initial increase in NO production in portal hypertension.

PMID- 12003816
TI  - Parasympathetic effects on cardiac electrophysiology during exercise and
      recovery.
AB  - Depressed parasympathetic tone is associated with an increased risk of sudden
      cardiac death. Exercise and the postexercise recovery period, which are
      associated with parasympathetic withdrawal, are high risk periods for sudden
      death. However, parasympathetic effects on cardiac electrophysiology during
      exercise and recovery have not been described. Electrophysiology studies were
      performed using noninvasive programmed stimulation (NIPS) in nine subjects (age
      59 +/- 18 yr) with implanted dual-chamber devices and normal left ventricular
      function during multiple bicycle exercise sessions. NIPS was performed at rest,
      during exercise, and in the early recovery period both before and after
      parasympathetic blockade with atropine. Parasympathetic effect was defined as the
      value of the parameter of interest in the absence of atropine minus the value of
      the parameter in the presence of atropine. During exercise, sinus cycle length,
      atrioventricular (AV) block cycle length, AV interval, and ventricular effective
      refractory period shortened; in recovery, the values were intermediate between
      the rest and exercise values (P < 0.0001 by ANOVA). Parasympathetic effects on
      sinus cycle length, AV block cycle length, AV interval, and ventricular effective
      refractory period were 247 +/- 140, 58 +/- 20, 76 +/- 20, and 8.6 +/- 7.5 ms at
      rest, 106 +/- 20, 37 +/- 14, 24 +/- 13, and 2.6 +/- 7.8 ms during exercise, and
      209 +/- 114, 50 +/- 23, 35 +/- 21, and 9.5 +/- 11.8 ms during recovery,
      respectively. There was poor correlation among the parasympathetic effects noted
      at the sinus node, AV node, and ventricle. Further work evaluating
      parasympathetic effects on cardiac electrophysiology during exercise and recovery
      in patients with heart disease is required to elucidate its role in modulating
      the risk of sudden cardiac death noted at these times.

PMID- 12003817
TI  - Hemodynamics of anesthetized ventilated mouse models: aspects of anesthetics,
      fluid support, and strain.
AB  - This study evaluates the effects of anesthesia and fluid support on hemodynamic
      parameters of the mechanically ventilated mouse of four different strains. All
      experiments were performed at a similar surgical level of anesthesia, as
      indicated by the probing of the pedal withdrawal reflex. Three anesthetic
      regimens [fentanyl-fluanisone-midazolam (FFM), ketamine-medetomidine-atropine
      (KMA), and isoflurane (ISO)], four commonly used mouse strains (Swiss, CD-1,
      BalbC, and C57Bl6), and three different fluid support strategies (no fluid, 0.2
      ml x h(-1) x 10 g(-1) of 6% polystarch solution, and 0.5 ml x h(-1) x 10 g(-1)
      saline) were studied. Mean arterial pressure (MAP) or heart rate (HR) was similar
      among the four strains of mice except a trend toward lower HR for the BalbC mice.
      In terms of MAP, KMA is the preferred anesthetic for the Swiss and CD-1 mice,
      whereas KMA or ISO are recommended for BalbC or C57Bl6 mice. In terms of HR, ISO
      is the preferred anesthetic for the Swiss, CD-1, and C57Bl6 strains. No
      differences in HR for the three anesthetics were observed for the BalbC strain.
      Compared with administration of no fluid, both saline and polystarch
      administration similarly increased MAP by 7 +/- 2, 10 +/- 2, and 11 +/- 2 mmHg at
      t = 1, 2, and 3 h, respectively, whereas fluid administration was without effect
      on HR. Saline supplementation resulted in an increased dry-to-wet ratio of the
      heart and both fluid regimens decreased total hemoglobin in the blood from 12.6
      +/- 0.5 to 10.4 +/- 0.5 g/100 ml. Saline administration was associated with blood
      acidosis (pH 7.20 +/- 0.03) compared with the Haes (pH 7.29 +/- 0.02) or no-fluid
      group (pH 7.34 +/- 0.03), whereas PCO(2) was approximately 30 mmHg for all
      groups. We conclude that at similar surgical levels of anesthesia, the preferable
      type of anesthesia (ISO or KMA, but never FFM) depends on the strain used and
      whether MAP or HR is the focus of study. Additional fluid support is beneficial
      in terms of raising arterial blood pressure, although this is at the cost of
      changes in organ water content and increased anemia.

PMID- 12003818
TI  - P2X purinergic receptor channel expression and function in bovine aortic
      endothelium.
AB  - We examined bovine aortic endothelial cells (BAECs) for the functional expression
      of P2X receptors, the ATP-gated cation channels. We identified the P2X subtypes
      present in BAECs using RT-PCR. mRNA was present for only three of seven family
      members: P2X4, P2X5, and P2X7. We then characterized agonist-activated currents
      in whole cell and outside-out patch recordings using 2-methyl-thio-ATP (MeSATP)
      as a P2X4 and P2X5 receptor agonist and 2',3'-O-(4-benzoylbenzoyl)ATP (BzATP) as
      a P2X7 receptor agonist. MeSATP (10-20 microM) produced current with
      characteristics of P2X4 receptors. The current was an inwardly rectifying
      current, reversed near 0 mV, slowly desensitized, was not blocked by suramin (300
      microM) or reactive blue (60 microM), and had a single channel conductance of 36
      pS. BzATP (10-100 microM), on the other hand, activated a 9-pS channel with
      sustained activity in the continued presence of the agonist. BzATP-activated
      current was blocked by reactive blue (60 microM) and by suramin (approximately
      50% block at 300 microM). We confirmed, by immunocytochemistry, the presence of
      P2X4 and P2X7 protein. The agonists failed, however, to induce significant uptake
      of the large molecule YO-PRO, indicating the lack of pore development that has
      been demonstrated for P2X7 and P2X4 in response to agonist in some cell types.

PMID- 12003819
TI  - Natriuretic peptide receptor-B in adult rat ventricle is predominantly confined
      to the nonmyocyte population.
AB  - We assessed the cellular localization and relative concentration of the C-type
      natriuretic peptide (CNP) guanylate cyclase-B (GC-B) receptor in the adult rat
      heart ventricle by several techniques. In frozen sections of the ventricle, anti
      receptor antibody stained the vasculature and cells interstitial to myocytes, but
      not the myocytes themselves. The same antibody detected GC-B in immunoblots of
      protein extracts of nonmyocytes, but not myocytes and recognized an equivalent
      protein in extracts of cultured cardiac fibroblasts, but not A7r5 rat smooth
      muscle cells. In functional assays, CNP-induced cGMP accumulation per milligram
      cell protein was an order of magnitude greater in cultured cardiac fibroblasts
      than in A7r5 smooth muscle cells and two orders of magnitude greater than in
      freshly isolated cardiac myocytes. Modulation of cGMP accumulation by
      phosphodiesterases (PDEs) was cell specific as determined by antagonist
      pharmacological profiles, PDE1 in fibroblasts, PDE2 in A7r5 cells, and PDE3 in
      myocytes, suggesting that significant but low-level cGMP response to CNP measured
      in heart myocytes is not due to nonmyocyte contamination. Fibroblasts of cardiac
      origin do not show an interactive relationship between receptor responsiveness to
      CNP, cGMP levels, and proliferation-related mitogen-activated signal transduction
      pathways. Whereas previous reports suggest CNP exerts significant effects in
      neonatal rat cardiomyocytes, our results suggest that fibroblasts are likely the
      most responsive cell type (cGMP production) in the adult rat heart.

PMID- 12003820
TI  - Paradoxical overexpression and translocation of connexin43 in homocysteine
      treated endothelial cells.
AB  - Hyperhomocysteinemia is an established cause of defective vasorelaxation. Gene
      expression screening of human umbilical vein endothelial cells (HUVEC) treated
      with homocysteine (Hcy) revealed that connexin43 (Cx43) was upregulated.
      Expression of Cx43 was increased more than twofold in Hcy-treated HUVEC. Gap
      junctional communication (Lucifer yellow and whole cell patch clamp) was not
      enhanced in Hcy-treated HUVEC. HUVEC expressing chimeric Cx43-green fluorescent
      protein exhibited it at cell-cell contacts in control but showed redistribution
      to the intracellular compartment(s) in Hcy-treated cells. Confocal microscopy of
      HUVEC stained with anti-Cx43, mitochondrial, and endoplasmic reticulum
      fluorescent markers showed the localization of Cx43 to the plasma membrane of
      control cells and its colocalization with the mitochondrial marker in Hcy-treated
      HUVEC. Studies of isolated mitochondria confirmed overexpression of Cx43 in the
      mitochondria of Hcy-treated HUVEC. Microdissected renal interlobar arteries,
      which normally exhibit endothelium-derived hyperpolarizing factor-induced
      vasorelaxation, showed reduced nitric oxide synthase- and cyclooxygenase
      independent vasorelaxation to acetylcholine after pretreatment with Hcy. In
      summary, Hcy-induced upregulation of Cx43 transcript and protein expression are
      associated with unaltered intercellular communication, redistribution of Cx43 in
      HUVEC, and reduced nitric oxide- and prostanoid-independent vascular responses to
      acetylcholine in Hcy-treated arteries.

PMID- 12003821
TI  - Impact of anesthesia on cardiac function during echocardiography in mice.
AB  - Anesthetics provide sedation and immobility facilitating echocardiography in
      mice, but influence cardiac function. We studied the effects of intraperitoneal
      and inhaled anesthetic agents on echocardiographic measurements. Mice were
      anesthetized with intraperitoneal tribromoethanol (TBE), ketamine-midazolam
      (K/M), ketamine-xylazine (K/X), or inhaled isoflurane (Isf), and
      echocardiographic parameters were assessed at 5, 10, 15, and 20 min. In C57BL/6N
      mice, Isf produced high initial heart rates (HR) that decreased to levels
      comparable to TBE at 15-20 min (approximately 450 beats/min) and the most stable
      percent fractional shortening (%FS) and end-diastolic dimension (EDD). With TBE,
      %FS initially was low, but increased comparable to Isf (approximately 45%) at 15
      min. K/M produced similar time trends but lower absolute values compared with TBE
      for all parameters. K/X produced cardiac depression evidenced by low HR and %FS,
      and increased EDD. Isf was the most reproducible in repeat studies at 12 days. In
      C57BL/6J compared with C57BL/6N mice, K/M produced higher HR, and %FS and TBE
      produced smaller EDD. In conclusion, anesthetic agent, timing of
      echocardiographic measurements, and genetic background are all critical variables
      during echocardiography in mice.

PMID- 12003822
TI  - Mechanisms of shock-induced arrhythmogenesis during acute global ischemia.
AB  - Little is known about the mechanisms of vulnerability and defibrillation under
      ischemic conditions. We investigated these mechanisms in 18 Langendorff-perfused
      rabbit hearts during 75% reduced-flow ischemia. Electrical activity was optically
      mapped from the anterior epicardium during right ventricular shocks applied at
      various phases of the cardiac cycle while the excitation-contraction decoupler
      2,3-butanedione monoxime (BDM; 15 mM) was used to suppress motion artifacts
      caused by contraction of the heart. During ischemia, vulnerable window width
      increased [from 30-90% of the action potential duration (APD) in the control to 
      10 to 100% of the APD in ischemia]. Moreover, arrhythmia severity increased along
      with the reduction of APD (176 +/- 9 ms in control and 129 +/- 26 ms in ischemia,
      P < 0.01) and increased dispersion of repolarization (45 +/- 17 ms in control and
      73 +/- 28 ms in ischemia, P < 0.01). Shock-induced virtual electrode polarization
      was preserved. Depolarizing (contrary to hyperpolarizing) response time constants
      increased. Virtual electrode-induced wavefronts of excitation had much more
      tortuous pathways leading to wavefront fractionation. Defibrillation failure at
      all shock strengths was observed in four hearts. Optical mapping revealed that
      the shock extinguished the arrhythmia; however, the arrhythmia self-originated
      after an isoelectric window of 339 +/- 189 ms. In conclusion, in most cases,
      virtual electrode-induced phase singularity (VEIPS) was responsible for shock
      induced arrhythmogenesis during acute global ischemia. Enhancement of
      arrhythmogenesis was associated with an increased dispersion of repolarization
      and altered deexcitation. In four hearts, arrhythmogenesis could not be explained
      by VEIPS.

PMID- 12003823
TI  - Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular
      diastolic function.
AB  - Mast cells contain proteases capable of activating matrix metalloproteinases
      (MMPs). However, given the relatively low density of mast cells in the myocardium
      (i.e., 1.5-5.3 cells/mm(2)), it is unknown whether these enzymes are present in
      sufficient quantities in the normal heart to mediate MMP activation. Accordingly,
      this study sought to determine whether chemically induced degranulation of
      cardiac mast cells (with compound 48/80) would have an effect in isolated, blood
      perfused, functioning rat hearts. Mast cell degranulation produced a 15% increase
      in histamine levels present in the coronary efflux, a significant increase in
      myocardial water (i.e., edema) relative to normal values (80.1 +/- 3.4% vs. 77.4
      +/- 1.08%, P < or = 0.03), a substantial activation of MMP-2 (126% increase
      relative to controls, P < or = 0.02), and a marked decrease in myocardial
      collagen volume fraction (0.46 +/- 0.10% vs. 0.97 +/- 0.33%, P < or = 0.001).
      Furthermore, although an increase in ventricular stiffness was expected due to
      the extent of edema resulting from mast cell degranulation, modest ventricular
      dilatation was observed. These findings clearly demonstrate that the number of
      mast cells present in normal hearts is sufficient to mediate activation of MMPs
      and produce extracellular matrix degradation, thereby potentially causing
      subsequent ventricular dilatation.

PMID- 12003824
TI  - Involvement of inducible nitric oxide synthase in cardiac dysfunction with tumor
      necrosis factor-alpha.
AB  - Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis
      factor (TNF)-alpha develop dilated cardiomyopathy with myocardial inflammation.
      The purpose of this study was to investigate the role of nitric oxide (NO) in
      this mouse model of cardiomyopathy. Female TG and wild-type mice at the age of 10
      wk were studied. The expression and activity of inducible NO synthase (iNOS) were
      significantly increased in the TG myocardium, whereas those of endothelial NOS
      were not altered. The majority of the iNOS protein was isolated in the
      interstitial cells. The selective iNOS inhibitor (1S,5S,6R,7R)- 7-chloro-3-imino
      5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride (ONO-1714) was used to examine
      the effects of iNOS induction on myocardial contractility. Echocardiography and
      left ventricular pressure measurements were performed. Both fractional shortening
      and the maximum rate of rise of left ventricular pressure were significantly
      suppressed in TG mice. Although ONO-1714 did not change hemodynamic parameters or
      contractility at baseline, it significantly improved beta-adrenergic inotropic
      responsiveness in TG mice. These results indicate that induction of iNOS may play
      an important role in the pathogenesis of cardiac dysfunction in this mouse model
      of cytokine-induced cardiomyopathy.

PMID- 12003825
TI  - Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial
      function.
AB  - The present study was designed to investigate the interaction between 5
      methyltetrahydrofolate and tetrahydrobiopterin in modulating endothelial
      function. Tetrahydrobiopterin is a critical cofactor for nitric oxide synthase
      and maintains this enzyme as a nitric oxide- versus superoxide-producing enzyme.
      The structure of 5-methyltetrahydrofolate is similar to tetrahydrobiopterin and
      both agents have been shown to improve endothelium-dependent vasodilatation. We
      hypothesized that 5-methyltetrahydrofolate interacts with nitric oxide synthase
      in a fashion analogous, yet independent, of tetrahydrobiopterin to improve
      endothelial function. We demonstrate that 5-methyltetrahydrofolate binds the
      active site of nitric oxide synthase and mimics the orientation of
      tetrahydrobiopterin. Furthermore, 5-methyltetrahydrofolate attenuates superoxide
      production (induced by inhibition of tetrahydrobiopterin synthesis) and improves
      endothelial function in aortae isolated from tetrahydrobiopterin-deficient rats.
      We suggest that 5-methyltetrahydrofolate directly interacts with nitric oxide
      synthase to promote nitric oxide (vs. superoxide) production and improve
      endothelial function. 5-Methyltetrahydrofolate may represent an important
      strategy for intervention aimed at improving tetrahydrobiopterin bioavailability.

PMID- 12003826
TI  - Constitutive properties of hypertrophied myocardium: cellular contribution to
      changes in myocardial stiffness.
AB  - Recent studies have suggested that pressure overload hypertrophy (POH) alters the
      viscoelastic properties of individual cardiocytes when studied in isolation.
      However, whether these changes in cardiocyte properties contribute causally to
      changes in the material properties of the cardiac muscle as a whole is unknown.
      Accordingly, a selective, isolated, acute change in cardiocyte constitutive
      properties was imposed in an in vitro system capable of measuring the resultant
      effect on the material properties of the composite cardiac muscle. POH caused an
      increase in both myocardial elastic stiffness, from 20.5 +/- 1.3 to 28.4 +/- 1.8,
      and viscous damping, from 15.2 +/- 1.1 to 19.8 +/- 1.5 s (normal vs. POH, P <
      0.05), respectively. Recent studies have shown that cardiocyte constitutive
      properties could be acutely altered by depolymerizing the microtubules with
      colchicine. Colchicine caused a significant decrease in the viscous damping in
      POH muscles (19.8 +/- 1.5 s at baseline vs. 14.7 +/- 1.3 s after colchicine, P <
      0.05). Therefore, myocardial material properties can be altered by selectively
      changing the constitutive properties of one element within this muscle tissue,
      the cardiocyte. Changes in the constitutive properties of the cardiocytes
      themselves contribute to the abnormalities in myocardial stiffness and viscosity
      that develop during POH.

PMID- 12003827
TI  - Targeted deletion of adenosine A(3) receptors augments adenosine-induced coronary
      flow in isolated mouse heart.
AB  - To determine whether adenosine A(3) receptors participate in adenosine-induced
      changes in coronary flow, isolated hearts from wild-type (WT) and A(3) receptor
      knockout (A(3)KO) mice were perfused under constant pressure and effects of
      nonselective and selective agonists were examined. Adenosine and the selective
      A(2A) agonist 2-[p-(2-carboxyethyl)]phenylethylamino-5'-N
      ethylcarboxamidoadenosine (CGS-21680) produced augmented maximal coronary
      vasodilation in A(3)KO hearts compared with WT hearts. Selective activation of
      A(3) receptors with 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide
      (Cl-IB-MECA) at nanomolar concentrations did not effect coronary flow, but at
      higher concentrations it produced coronary vasodilation both in WT and A(3)KO
      hearts. Cl-IB-MECA-induced increases in coronary flow were susceptible to both
      pharmacological blockade and genetic deletion of A(2A) receptors. Because
      deletion or blockade of adenosine A(3) receptors augmented coronary flow induced
      by nonselective adenosine and the selective A(2A) receptor agonist CGS-21680, we
      speculate that this is due to removal of an inhibitory influence associated with
      the A(3) receptor subtype. These data indicate that the presence of adenosine
      A(3) receptors may either inhibit or negatively modulate coronary flow mediated
      by other adenosine receptor subtypes.

PMID- 12003828
TI  - Heart size-independent analysis of myocardial function in murine pressure
      overload hypertrophy.
AB  - Pressure overload cardiac hypertrophy may be a compensatory mechanism to
      normalize systolic wall stress and preserve left ventricular (LV) function. To
      test this concept, we developed a novel in vivo method to measure myocardial
      stress (sigma)-strain (epsilon) relations in normal and hypertrophied mice. LV
      volume was measured using two pairs of miniature omnidirectional piezoelectric
      crystals implanted orthogonally in the endocardium and one crystal placed on the
      anterior free wall to measure instantaneous wall thickness. Highly linear sigma
      epsilon relations were obtained in control (n = 7) and hypertrophied mice
      produced by 7 days of transverse aortic constriction (TAC; n = 13).
      Administration of dobutamine in control mice significantly increased the load
      independent measure of LV contractility, systolic myocardial stiffness. In TAC
      mice, systolic myocardial stiffness was significantly greater than in control
      mice (3,156 +/- 1,433 vs. 1,435 +/- 467 g/cm(2), P < 0.01), indicating enhanced
      myocardial contractility with pressure overload. However, despite the increased
      systolic performance, both active (time constant of LV pressure decay) and
      passive (diastolic myocardial stiffness constant) diastolic properties were
      markedly abnormal in TAC mice compared with control mice. These data suggest that
      the development of cardiac hypertrophy is associated with a heightened
      contractile state, perhaps as an early compensatory response to pressure
      overload.

PMID- 12003829
TI  - Nitric oxide production is maintained in exercising swine with chronic left
      ventricular dysfunction.
AB  - Left ventricular (LV) dysfunction caused by myocardial infarction (MI) is
      accompanied by endothelial dysfunction, most notably a loss of nitric oxide (NO)
      availability. We tested the hypothesis that endothelial dysfunction contributes
      to impaired tissue perfusion during increased metabolic demands as produced by
      exercise, and we determined the contribution of NO to regulation of regional
      systemic, pulmonary, and coronary vasomotor tone in exercising swine with LV
      dysfunction produced by a 2- to 3-wk-old MI. LV dysfunction resulted in blunted
      systemic and coronary vasodilator responses to ATP, whereas the responses to
      nitroprusside were maintained. Exercise resulted in blunted systemic and
      pulmonary vasodilator responses in MI that resembled the vasodilator responses in
      normal (N) swine following blockade of NO synthase with N(omega)-nitro-L-arginine
      (L-NNA, 20 mg/kg iv). However, L-NNA resulted in similar decreases in systemic
      (43 +/- 3% in N swine and 49 +/- 4% in MI swine), pulmonary (45 +/- 5% in N swine
      and 49 +/- 4% in MI swine), and coronary (28 +/- 4% in N and 35 +/- 3% in MI)
      vascular conductances in N and MI swine under resting conditions; similar effects
      were observed during treadmill exercise. Selective inhibition of inducible NO
      synthase with aminoguanidine (20 mg/kg iv) had no effect on vascular tone in MI.
      These findings indicate that while agonist-induced vasodilation is already
      blunted early after myocardial infarction, the contribution of endothelial NO
      synthase-derived NO to regulation of vascular tone under basal conditions and
      during exercise is maintained.

PMID- 12003830
TI  - Attenuated sympathetic nerve responses after 24 hours of bed rest.
AB  - Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of
      this phenomenon remains unclear. In this report we examined hemodynamic and
      sympathetic nerve responses to graded lower body negative pressure (LBNP) before
      and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a
      graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume
      obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a
      progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg
      every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP
      tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002),
      cardiac output was unchanged, and the ability to augment MSNA at high levels of
      LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073
      bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P
      < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve
      responses to LBNP.

PMID- 12003831
TI  - Effect of endurance training on coronary artery size and function in healthy men:
      an invasive followup study.
AB  - In eight healthy male volunteers (cardiologists; age 36 +/- 5 yr), bicycle
      spiroergometry, Doppler echocardiography, and quantitative coronary angiography
      with intracoronary Doppler measurements before and after completion of a physical
      endurance exercise program of >5 mo duration were performed. Maximum oxygen
      uptake increased from 46 +/- 6 to 54 +/- 5 ml x kg(-1) x min(-1) (P = 0.04),
      maximum ergometric workload changed from 3.8 +/- 0.3 to 4.4 +/- 0.3 W/kg (P =
      0.001), and left ventricular mass index increased from 82 +/- 18 to 108 +/- 29
      g/m(2) (P = 0.001). The right, left main, and left anterior descending coronary
      artery cross-sectional area increased significantly in response to exercise.
      Before versus at the end of the exercise program, flow-induced left anterior
      descending coronary artery cross-sectional area was 10.1 +/- 3.5 and 11.0 +/- 3.9
      mm(2), respectively (P = 0.03), nitroglycerin-induced left coronary calibers
      increased significantly, and coronary flow velocity reserve changed from 3.8 +/-
      0.8 to 4.5 +/- 0.7 (P = 0.001). Left coronary artery correlated significantly
      with ventricular mass and maximum oxygen uptake, and coronary flow velocity
      reserve was significantly associated with maximum workload.

PMID- 12003832
TI  - Balance between myogenic, flow-dependent, and metabolic flow control in coronary
      arterial tree: a model study.
AB  - Myogenic response, flow-dependent dilation, and direct metabolic control are
      important mechanisms controlling coronary flow. A model was developed to study
      how these control mechanisms interact at different locations in the arteriolar
      tree and to evaluate their contribution to autoregulatory and metabolic flow
      control. The model consists of 10 resistance compartments in series, each
      representing parallel vessel units, with their diameters determined by tone
      depending on either flow and pressure [flow-dependent tone reduction factor
      (TRF(flow)) x Tone(myo)] or directly on metabolic factors (Tone(meta)). The
      pressure-Tone(myo) and flow-TRF(flow) relations depend on the vessel size
      obtained from interpolation of data on isolated vessels. Flow-dependent dilation
      diminishes autoregulatory properties compared with pressure-flow lines obtained
      from vessels solely influenced by Tone(myo). By applying Tone(meta) to the four
      distal compartments, the autoregulatory properties are restored and tone is
      equally distributed over the compartments. Also, metabolic control and blockage
      of nitric oxide are simulated. We conclude that a balance is required between the
      flow-dependent properties upstream and the constrictive metabolic properties
      downstream. Myogenic response contributes significantly to flow regulation.

PMID- 12003833
TI  - Left ventricular resynchronization therapy in a canine model of left bundle
      branch block.
AB  - Positive responses to left (LV) and biventricular (BV) stimulation observed in
      heart failure patients with left bundle branch block (LBBB) suggest a possible
      mechanism of LV resynchronization. An anesthetized canine LBBB model was
      developed using radio frequency ablation. Before and after ablation, LV pressure
      derivative over time (dP/dt) and aortic pulse pressure (PP) were assessed during
      normal sinus rhythm with right ventricle (RV), LV, or BV stimulation combined
      with four atrioventricular delays in six dogs. In three more dogs, M-mode
      echocardiograms of septal and LV posterior wall motion were obtained before and
      after LBBB and during LV stimulation. LBBB caused QRS widening and hemodynamics
      deterioration. Before ablation, stimulation alone worsened LV dP/dt and PP. After
      ablation, LV and BV stimulation maximally increased LV dP/dt by 16% and PP by 7%
      (P < 0.001), whereas little improvement was observed during RV stimulation. M
      mode echocardiogram showed that LBBB resulted in a paradoxical septal wall motion
      that was corrected by LV stimulation. In conclusion, LV and BV stimulation
      improved cardiac function in a canine LBBB model via resynchronization of LV
      excitation and contraction.

PMID- 12003834
TI  - Model of nitric oxide diffusion in an arteriole: impact of hemoglobin-based blood
      substitutes.
AB  - Administration of hemoglobin-based oxygen carriers (HBOCs) frequently results in
      vasoconstriction that is primarily attributed to the scavenging of endothelium
      derived nitric oxide (NO) by cell-free hemoglobin. The ensuing pressor response
      could be caused by the high NO reactivity of HBOC in the vascular lumen and/or
      the extravasation of hemoglobin molecules. There is a need for quantitative
      understanding of the NO interaction with HBOC in the blood vessels. We developed
      a detailed mathematical model of NO diffusion and reaction in the presence of an
      HBOC for an arteriolar-size vessel. The HBOC reactivity with NO and degree of
      extravasation was studied in the range of 2-58 x 10(6) M(-1) x s(-1) and 0-100%,
      respectively. The model predictions showed that the addition of HBOC reduced the
      smooth muscle (SM) NO concentration in the activation range (12-28 nM) for
      soluble guanylate cyclase, a major determinant of SM contraction. The SM NO
      concentration was significantly reduced when the extravasation of HBOC molecules
      was considered. The myoglobin present in the parenchymal cells scavenges NO,
      which reduces the SM NO concentration.

PMID- 12003835
TI  - Differential ANG II generation in plasma and tissue of mice with decreased
      expression of the ACE gene.
AB  - We utilized mice with homozygous disruption of angiotensin-converting enzyme
      (ACE) (-/-), mice with heterozygous deletion of ACE (+/-), and wild-type mice
      (+/+) to test the hypothesis that genetic variation in ACE modulates tissue and
      plasma angiotensin (ANG) II concentrations. With the use of ANG I as substrate,
      kidney, heart, and lung ACE activity was reduced 80% in -/- mice compared with
      +/+ mice. However, ANG II concentrations and ANG II-to-ANG I ratios in the
      kidney, heart, and lung did not differ among genotypes. In contrast, plasma ANG
      II concentrations in -/- mice were <2 fmol/ml, whereas plasma ANG I
      concentrations were extremely high (765 fmol/ml). Chymase activity was increased
      14-fold in the kidney (P < 0.05) and 1.5-fold in the heart (P < 0.05) of -/-
      versus +/+ mice but did not differ among genotypes in the lung. ANG II formation
      from enzymes other than ACE and chymase contributed <2% of total ANG II formation
      in all genotypes. These data suggest that ACE is essential to ANG II formation in
      the vascular space, whereas chymase may provide an important mechanism in
      maintaining steady-state ANG II levels in tissue.

PMID- 12003836
TI  - Activation time of myocardial oxidative phosphorylation in creatine kinase and
      adenylate kinase knockout mice.
AB  - Our goal was to determine whether mice genetically altered to lack either
      creatine kinase (M/MtCK(-/-)) or adenylate kinase (AK(-/-)) show altered
      properties in the dynamic regulation of myocardial oxygen consumption (MVO(2)).
      We measured contractile function, oxygen consumption, and the mean response time
      of oxygen consumption to a step increase in heart rate [i.e., mitochondrial
      response time (t(mito))] in isolated Langendorff-perfused hearts from wild-type
      (n = 6), M/MtCK(-/-) (n = 6), and AK(-/-) (n = 4) mice. Left ventricular
      developed pressure was higher in M/MtCK(-/-) hearts (88.2 +/- 6.8 mmHg) and lower
      in AK(-/-) hearts (46.7 +/- 9.4 mmHg) compared with wild-type hearts (60.7 +/-
      10.1 mmHg) at the basal pacing rate. Developed pressure fell slightly when heart
      rate was increased in all three groups. Basal MVO(2) at 300 beats/min was 19.1 +/
      2.4, 19.4 +/- 1.5, and 16.3 +/- 1.9 micromol x min(-1) x g dry wt(-1) for
      M/MtCK(-/-), AK(-/-), and wild type, respectively, which increased to 25.5 +/-
      3.7, 25.4 +/- 2.6, and 22.0 +/- 2.6 micromol. min(-1) x g(-1), when heart rate
      was increased to 400 beats/min. The t(mito) was significantly faster in M/MtCK(-/
      ) hearts: 3.0 +/- 0.3 versus 7.3 +/- 0.6 and 8.0 +/- 0.4 s for M/MtCK(-/-), AK(-/
      ), and wild-type hearts, respectively. Our results demonstrate that MVO(2) of
      M/MtCK(-/-) hearts adapts more quickly to an increase in heart rate and thereby
      support the hypothesis that creatine kinase acts as an energy buffer in the
      cytosol, which delays the energy-related signal between sites of ATP hydrolysis
      and mitochondria.

PMID- 12003837
TI  - Erythrocyte consumption of nitric oxide in presence and absence of plasma-based
      hemoglobin.
AB  - Experimental measurements have suggested a consumption rate of nitric oxide (NO)
      by red blood cells (RBCs) that is orders of magnitude smaller than that of an
      equivalent concentration of free hemoglobin in solution. This difference has been
      attributed to external diffusion limitations in the transport of NO from the
      plasma to the surface of the RBC or to resistance in the transport through the
      erythrocytic membrane. A detailed mathematical model is developed to quantify the
      resistance to NO transport around a single RBC and to predict the consumption
      rate in the presence and absence of extracellular hemoglobin. We provide a
      description for the NO consumption rate as a function of hematocrit, RBC radius,
      membrane permeability, and extracellular hemoglobin concentration. We predict a
      first-order rate constant for NO consumption in blood between 7.5 x 10(2) and 6.5
      x 10(3) s(-1) at a hematocrit of 45% for membrane permeability values between 0.1
      and 40 cm/s. Our results suggest that the difference in NO uptake by RBCs and
      free hemoglobin is smaller than previously reported and it is hematocrit
      dependent.

PMID- 12003838
TI  - Inhibition of NO production increases myocardial blood flow and oxygen
      consumption in congestive heart failure.
AB  - Coronary blood flow (CBF) and myocardial oxygen consumption (MVO(2)) are reduced
      in dogs with pacing-induced congestive heart failure (CHF), which suggests that
      energy metabolism is downregulated. Because nitric oxide (NO) can inhibit
      mitochondrial respiration, we examined the effects of NO inhibition on CBF and
      MVO(2) in dogs with CHF. CBF and MVO(2) were measured at rest and during
      treadmill exercise in 10 dogs with CHF produced by rapid ventricular pacing
      before and after inhibition of NO production with N(G)-nitro-L-arginine (L-NNA,
      10 mg/kg iv). The development of CHF was accompanied by decreases in aortic and
      left ventricular (LV) systolic pressure and an increase in LV end-diastolic
      pressure (25 +/- 2 mmHg). L-NNA increased MVO(2) at rest (from 3.07 +/- 0.61 to
      4.15 +/- 0.80 ml/min) and during exercise; this was accompanied by an increase in
      CBF at rest (from 31 +/- 2 to 40 +/- 4 ml/min) and during exercise (both P <
      0.05). Although L-NNA significantly increased LV systolic pressure, similar
      increases in pressure produced by phenylephrine did not increase MVO(2). The
      findings suggest that NO exerts tonic inhibition on respiration in the failing
      heart.

PMID- 12003839
TI  - Ischemia alters the electrical activity of pacemaker cells isolated from the
      rabbit sinoatrial node.
AB  - The purpose of this study was to investigate the mechanisms responsible for
      ischemia-induced changes in spontaneous electrical activity. An ischemic-like
      Tyrode solution (pH 6.6) reversibly depolarized the maximum diastolic potential
      (MDP) and reduced the action potential (AP) overshoot (OS). We used SNARF-1,
      which is an indicator of intracellular pH (pH(i)), and perforated-patch
      techniques to test the hypothesis that acidosis caused these effects. Acidic but
      otherwise normal Tyrode solution (pH 6.8) produced similar effects. Basic Tyrode
      solution (pH 8.5) hyperpolarized the MDP, shortened the AP, and slowed the firing
      rate. In the presence of "ischemic" Tyrode solution, hyperpolarizing current
      restored the MDP and OS to control values. HOE-642, an inhibitor of Na/H
      exchange, did not alter pH(i) or electrical activity and did not prevent the
      effects of ischemic Tyrode solution or recovery after washout. Time-independent
      net inward current but not hyperpolarization-activated inward current was
      enhanced by ischemic Tyrode solution or by 30 microM BaCl(2), a selective blocker
      of inward-rectifying K currents at this concentration. The results suggest that
      1) acidosis was responsible for the ischemia-induced effects but Na/H exchange
      was not involved, 2) the OS was reduced because of depolarization-induced
      inactivation of inward currents that generate the AP upstroke, and 3) reduction
      of an inward-rectifying outward K current contributed to the depolarization.

PMID- 12003840
TI  - A computationally efficient electrophysiological model of human ventricular
      cells.
AB  - Recent experimental and theoretical results have stressed the importance of
      modeling studies of reentrant arrhythmias in cardiac tissue and at the whole
      heart level. We introduce a six-variable model obtained by a reformulation of the
      Priebe-Beuckelmann model of a single human ventricular cell. The reformulated
      model is 4.9 times faster for numerical computations and it is more stable than
      the original model. It retains the action potential shape at various frequencies,
      restitution of action potential duration, and restitution of conduction velocity.
      We were able to reproduce the main properties of epicardial, endocardial, and M
      cells by modifying selected ionic currents. We performed a simulation study of
      spiral wave behavior in a two-dimensional sheet of human ventricular tissue and
      showed that spiral waves have a frequency of 3.3 Hz and a linear core of
      approximately 50-mm diameter that rotates with an average frequency of 0.62
      rad/s. Simulation results agreed with experimental data. In conclusion, the
      proposed model is suitable for efficient and accurate studies of reentrant
      phenomena in human ventricular tissue.

PMID- 12003841
TI  - Estrogen modulation of eNOS activity and its association with caveolin-3 and
      calmodulin in rat hearts.
AB  - Previous studies have shown that estrogen modulation of endothelial nitric oxide
      (NO) synthase (eNOS) may confer protection against heart disease. Here, we
      demonstrate an association between reductions in baroreflex-mediated bradycardia
      and in cardiac NOS activity in ovariectomized (Ovx) rats compared with controls.
      The latter resulted, at least in part, from a reduction in cardiac eNOS protein.
      eNOS-derived NO and its biological effects are determined by the levels of eNOS
      protein and by eNOS catalytic activity; the latter is regulated partly through
      the dynamic interaction with an inhibitory protein (caveolin) and a stimulatory
      protein (calmodulin). The association of eNOS immunoprecipitated with caveolin-3
      and calmodulin was examined. Caveolin-3 and calmodulin binding with eNOS was
      increased and decreased, respectively, in Ovx rats. 17 beta-Estradiol replacement
      restored, to within normal levels, the baroreflex-mediated bradycardic responses
      along with eNOS activity, eNOS expression, and the association of eNOS with
      caveolin-3 and calmodulin. Our findings may help to elucidate the molecular
      mechanism underlying the favorable effects of estrogen on cardiac responses to
      baroreflex activation.

PMID- 12003842
TI  - Escherichia coli LPS-induced LV dysfunction: role of toll-like receptor-4 in the
      adult heart.
AB  - The precise molecular mechanisms responsible for sepsis-induced myocardial
      dysfunction remain undefined. Toll-like receptor-4 (TLR-4) engages
      lipopolysaccharide (LPS) and activates signaling pathways leading to the
      expression of proinflammatory cytokines implicated in myocardial dysfunction. We
      determined whether TLR-4 was necessary for LPS-induced myocardial dysfunction in
      vivo. The effects of LPS on left ventricular (LV) function were studied in mice
      with defective TLR-4 signaling (C3H/HeJ, TLR-4 deficient) and wild-type mice
      (C3HeB/FeJ). Mice (n = 5/group) were injected with LPS or diluent, and LV
      function was examined by using two-dimensional echocardiography and conductance
      catheters. LPS significantly decreased all indexes of LV function in wild-type
      mice when compared with controls; LV function was not depressed in the LPS
      treated TLR-4-deficient mice relative to controls. LPS increased myocardial
      nitric oxide synthase-2 expression and cGMP only in wild-type mice. This study
      suggests that TLR-4 mediates the LV dysfunction that occurs in LPS-induced shock.
      Therefore, TLR-4 might be a therapeutic target for attenuating the effects of LPS
      on the heart.

PMID- 12003843
TI  - Viscoelastic properties of pressure overload hypertrophied myocardium: effect of
      serine protease treatment.
AB  - To determine whether and to what extent one component of the extracellular
      matrix, fibrillar collagen, contributes causally to abnormalities in
      viscoelasticity, collagen was acutely degraded by activation of endogenous matrix
      metalloproteinases (MMPs) with the serine protease plasmin. Papillary muscles
      were isolated from normal cats and cats with right ventricular pressure overload
      hypertrophy (POH) induced by pulmonary artery banding. Plasmin treatment caused
      MMP activation, collagen degradation, decreased the elastic stiffness constant,
      and decreased the viscosity constant in both normal and POH muscles. Thus,
      whereas many mechanisms may contribute to the abnormalities in myocardial
      viscoelasticity in the POH myocardium, changes in fibrillar collagen appear to
      play a predominant role.

PMID- 12003844
TI  - alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult
      spontaneously hypertensive rats.
AB  - We examined the effect of alpha(2)-adrenoreceptor blockade in the nucleus of the
      solitary tract (NTS) on baroreflex responses elicited by electrical stimulation
      of the left aortic depressor nerve (ADN) in urethane-anesthetized spontaneously
      hypertensive rats (SHR, n = 11) and normotensive Wistar-Kyoto rats (WKY, n = 11).
      ADN stimulation produced a frequency-dependent decrease in mean arterial pressure
      (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). In SHR,
      unilateral microinjection of idazoxan into the NTS markedly reduced baroreflex
      control of MAP, RSNA, and HR and had a disproportionately greater influence on
      baroreflex control of MAP than of RSNA. In WKY, idazoxan microinjections did not
      significantly alter baroreflex function relative to control vehicle injections.
      These results suggest that baroreflex regulation of arterial pressure in SHR is
      highly dependent on NTS adrenergic mechanisms. The reflex regulation of
      sympathetic outflow to the kidney is less influenced by the altered alpha(2)
      adrenoreceptor mechanisms in SHR.

PMID- 12003845
TI  - Glutathione and K(+) channel remodeling in postinfarction rat heart.
AB  - Electrical remodeling of the diseased ventricle is characterized by
      downregulation of K(+) channels that control action potential repolarization.
      Recent studies suggest that this shift in electrophysiological phenotype involves
      oxidative stress and changes in intracellular glutathione (GSH), a key regulator
      of redox-sensitive cell functions. This study examined the role of GSH in
      regulating K(+) currents in ventricular myocytes from rat hearts 8 wk after
      myocardial infarction (MI). Colorimetric analysis of tissue extracts showed that
      endogenous GSH levels were significantly less in post-MI hearts compared with
      controls, which is indicative of oxidative stress. This change in GSH status
      correlated with significant decreases in activities of glutathione reductase and
      gamma-glutamylcysteine synthetase. Voltage-clamp studies of isolated myocytes
      from post-MI hearts demonstrated that downregulation of the transient outward
      K(+) current (I(to)) could be reversed by pretreatment with exogenous GSH or N
      acetylcysteine, a precursor of GSH. Upregulation of I(to) was also elicited by
      dichloroacetate, which increases glycolytic flux through the GSH-related pentose
      pathway. This metabolic effect was blocked by inhibitors of glutathione reductase
      and the pentose pathway. These data indicate that oxidative stress-induced
      alteration in the GSH redox state plays an important role in I(to) channel
      remodeling and that GSH homeostasis is influenced by pathways of glucose
      metabolism.

PMID- 12003846
TI  - QT-RR relationship in healthy subjects exhibits substantial intersubject
      variability and high intrasubject stability.
AB  - Recently, it was demonstrated that the QT-RR relationship pattern varies
      significantly among healthy individuals. We compared the intra- and
      interindividual variations of the QT-RR relationship. Twenty-four-hour 12-lead
      digital electrocardiograms (ECGs; SEER MC, GE Marquette; 10-s ECG recorded every
      30 s) were obtained at baseline and after 24 h, 1 wk, and 1 mo in 75 healthy
      subjects (42 women, 33 men, age 27.9 +/- 9.6 vs. 26.8 +/- 7.5 yr, P = not
      significant). QT interval was measured automatically in each ECG by six different
      algorithms, and the mean of the six measurements was analyzed. In each recording
      of each individual, QT-RR relationship was assessed by 10 different regression
      models including linear (QT = beta + alpha x RR) and parabolic (QT = beta x
      RR(alpha)) models. Standard deviations (SDs) of regression parameters alpha and
      beta of consecutive recordings of each individual were compared with SD of the
      individual means. Intrasubject stability and interindividual variability were
      further tested by ANOVA. With all models, intraindividual SDs of the regression
      parameters were highly significantly smaller than SD of individual means (P < 10(
      5)-10(-9)). The intrasubject stability was further confirmed by ANOVA (P < 10(
      19)-10(-30)). The QT-RR relationship exhibits substantial intersubject
      variability as well as a high intrasubject stability. This has practical
      implications for a precise estimation of the heart rate-corrected QT interval in
      which optimized subject-specific rate correction formulas should be used.

PMID- 12003847
TI  - Different alpha-adrenoceptors mediate migration of vascular smooth muscle cells
      and adventitial fibroblasts in vitro.
AB  - Norepinephrine directly induces growth of the vascular wall, which may involve
      not only proliferation of smooth muscle cells (SMCs) and adventitial fibroblasts
      (AFBs) but also augmentation of their migration. To test this hypothesis, growth
      arrested SMCs and AFBs from rat aorta were exposed to norepinephrine.
      Norepinephrine caused dose-dependent migration of both cell types that was
      dependent on chemotaxis. In contrast, platelet-derived growth factor (PDGF)-BB,
      used as a positive control, stimulated both chemotaxis and chemokinesis. Only
      alpha(1D)-adrenoceptors (AR) and alpha(2)-AR antagonists inhibited norepinephrine
      migration of SMCs, whereas norepinephrine migration of AFBs was only inhibited by
      alpha(1A)-AR and alpha(1B)-AR antagonists; beta-AR blockade was without effect.
      Norepinephrine and PDGF-BB were additive for AFB, but not SMC, migration.
      Stimulation of migration was reversed at high norepinephrine concentrations (10
      microM); this inhibition was mediated by alpha(2)- and beta-ARs in AFBs but not
      in SMCs. Thus norepinephrine induces migration of SMCs and AFBs via different
      alpha-ARs. This action may participate in wall remodeling and norepinephrine
      potentiation of injury-induced intimal lesion growth.

PMID- 12003848
TI  - Role of carbon monoxide in glutamate receptor-induced dilation of newborn pig
      pial arterioles.
AB  - The hypothesis that glutamate dilates pial arterioles of newborn pigs through the
      production of carbon monoxide (CO) was addressed. Anesthesized newborn pigs were
      equipped with cranial windows to measure pial arteriolar responses to stimuli.
      Heme oxygenase (HO) inhibitors added topically inhibited dilation to glutamate
      and to specific glutamate receptor agonists. The initial dilation to glutamate
      (10(-5) M) was 22% from baseline without an inhibitor and decreased to 9% with
      the HO inhibitor chromium mesoporphyrin (CrMP). Inhibition of dilation upon HO
      inhibition was similar when specific glutamate receptor agonists were employed.
      RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid caused 24% dilation
      from the baseline without an inhibitor, and the dilation was decreased to 1% with
      tin protoporphyrin (SnPP). (RS)-2-amino-3-(3-hydroxy-5-t-butylisoxazol-4
      yl)propionic acid (kainate receptors) caused dilation of 18% from baseline
      without an inhibitor, but only 2% when tin mesoporphyrin was applied. 1
      Aminocyclopropanecarboxylic acid (N-methyl-D-aspartate receptors) dilated pial
      arterioles 33% from baseline in control, but only to 2% in the presence of SnPP.
      Neither copper mesoporphyrin, which does not inhibit HO, nor light-inactivated
      CrMP affected the dilations. Furthermore, cerebral microvessels removed from the
      brain produced CO (stable isotope dilution gas chromatography-mass spectrometry),
      and this production was dose dependently increased by glutamate and inhibited by
      metal porphyrin HO inhibitors. These data suggest that dilation of newborn pig
      pial arterioles to glutamate and specific glutamate receptor agonists involves
      vascular production of CO. Additional cerebral sources of CO also could be
      stimulated by glutamate and contribute to the dilation.

PMID- 12003849
TI  - Diminished arteriolar responses in nitrate tolerance involve ROS and angiotensin
      II.
AB  - Our purpose was to evaluate hyporesponsivity to nitric oxide (NO)-induced
      dilation in small arterioles during nitrate tolerance. An Alza osmotic pump was
      implanted in the left flank of adult rats (n = 56) for continuous administration
      of nitroglycerin (140 microg/h) or vehicle (propylene glycol). On postoperative
      day 3, arcade (approximately 50-microm diameter) and terminal (approximately 20
      microm) arterioles were observed in the cremaster preparation with in vivo video
      microscopy. Local vascular responses were obtained with micropipette-applied NO
      donors, with and without superoxide dismutase (SOD), Mn(III) tetrakis(4-benzoic
      acid) porphyrin chloride (MnTBAP), or losartan. On day 3, NO-mediated dilation
      was significantly attenuated in nitroglycerin-treated rats. Attenuation was
      greater in the terminal arterioles compared with the arcades. Control responses
      were restored by SOD, MnTBAP, or losartan, suggesting a role for elevated
      angiotensin II and reactive oxygen species (ROS) as mediators of the attenuated
      NO dilation (nitrate tolerance). Addition of losartan to the drinking water
      likewise prevented nitrate tolerance. In summary, terminal arterioles are
      affected by nitrates to a greater extent than the arcade arterioles that feed
      them, in a process dependent on angiotensin II and ROS.

PMID- 12003850
TI  - Regional passive ventricular stress-strain relations during development of
      altered loads in chick embryo.
AB  - Mechanical load influences embryonic ventricular growth, morphogenesis, and
      function. However, little is known about changes in regional passive ventricular
      properties during the development of altered mechanical loading conditions in the
      embryo. We tested the hypothesis that regional mechanical loads are a critical
      determinant of embryonic ventricular passive properties. We measured biaxial
      passive right and left ventricular (RV and LV, respectively) stress-strain
      relations in chick embryos at Hamburger-Hamilton stages 21 and 27 after
      conotruncal banding (CTB) to increase biventricular pressure load or left atrial
      ligation (LAL) to reduce LV volume load and increase RV volume load. In the RV,
      wall strains at end-diastolic (ED) pressure normalized whereas ED stresses
      increased after either CTB or LAL during development. In the left ventricle, both
      ED strain and stress normalized after CTB, whereas both remained reduced with
      significantly increased myocardial stiffness after LAL. These results suggest
      that the embryonic ventricle adapts to chronically altered mechanical loading
      conditions by changing specific RV and LV passive properties. Thus regional
      mechanical load has a critical role during cardiogenesis.

PMID- 12003851
TI  - alpha-Adrenergic response and myofilament activity in mouse hearts lacking PKC
      phosphorylation sites on cardiac TnI.
AB  - Protein kinase C (PKC)-mediated phosphorylation of cardiac myofilament (MF)
      proteins has been shown to depress the actomyosin interaction and may be
      important during heart failure. Biochemical studies indicate that phosphorylation
      of Ser(43) and Ser(45) of cardiac troponin I (cTnI) plays a substantial role in
      the PKC-mediated depression. We studied intact and detergent-extracted papillary
      muscles from nontransgenic (NTG) and transgenic (TG) mouse hearts that express a
      mutant cTnI (Ser43Ala, Ser45Ala) that lacks specific PKC-dependent
      phosphorylation sites. Treatment of NTG papillary muscles with phenylephrine (PE)
      resulted in a transient increase and a subsequent 62% reduction in peak twitch
      force. TG muscles showed no transient increase and only a 45% reduction in force.
      There was a similar difference in maximum tension between NTG and TG fiber
      bundles that had been treated with a phorbol ester and had received subsequent
      detergent extraction. Although levels of cTnI phosphorylation correlated with
      these differences, the TG fibers also demonstrated a decrease in phosphorylation
      of cardiac troponin T. The PKC-specific inhibitor chelerythrine inhibited these
      responses. Our data provide evidence that specific PKC-mediated phosphorylation
      of Ser(43) and Ser(45) of cTnI plays an important role in regulating force
      development in the intact myocardium.

PMID- 12003852
TI  - Contribution of Ca(2+) transporters to relaxation in intact ventricular myocytes
      from developing rats.
AB  - The relative contributions of Ca(2+) transporters to intracellular Ca(2+)
      concentration ([Ca(2+)](i)) decline associated with twitch relaxation were
      analyzed in intact ventricular myocytes from developing and adult rats. This was
      accomplished by estimation of individual integrated Ca(2+) fluxes with the use of
      kinetic parameters calculated from [Ca(2+)](i) measurements during twitches and
      caffeine-evoked contractures, and from myocardial passive Ca(2+) buffering data.
      Our main findings were the following: 1) twitch relaxation and [Ca(2+)](i)
      decline were significantly slower during the first postnatal week than in adults,
      2) inhibition of sarcoplasmic reticulum (SR) Ca(2+) accumulation resulted in
      faster [Ca(2+)](i) decline in young cells than in adult cells, 3) the
      contributions of the SR Ca(2+) uptake and Na(+)/Ca(2+) exchange (NCX) to twitch
      relaxation increased from ~75 to 92%, and decreased from 24 to 5%, respectively,
      from birth to adulthood, and 4) Ca(2+) transport by the sarcolemmal Ca(2+)-ATPase
      was apparently increased in neonates. Our data indicate that despite a marked
      increase in NCX contribution to cell relaxation in immature rats, the SR Ca(2+)
      ATPase appears to be the predominant transporter responsible for relaxation
      associated [Ca(2+)](i) decline from birth to adulthood.

PMID- 12003853
TI  - Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of
      endothelium-dependent vasodilation.
AB  - High arterial blood oxygen tension increases vascular resistance, possibly
      related to an interaction between reactive oxygen species and endothelium-derived
      vasoactive factors. Vitamin C is a potent antioxidant capable of reversing
      endothelial dysfunction due to increased oxidant stress. We tested the hypotheses
      that hyperoxic vasoconstriction would be prevented by vitamin C, and that
      acetylcholine-mediated vasodilation would be blunted by hyperoxia and restored by
      vitamin C. Venous occlusion strain gauge plethysmography was used to measure
      forearm blood flow (FBF) in 11 healthy subjects and 15 congestive heart failure
      (CHF) patients, a population characterized by endothelial dysfunction and
      oxidative stress. The effect of hyperoxia on FBF and derived forearm vascular
      resistance (FVR) at rest and in response to intra-arterial acetylcholine was
      recorded. In both healthy subjects and CHF patients, hyperoxia-mediated increases
      in basal FVR were prevented by the coinfusion of vitamin C. In healthy subjects,
      hyperoxia impaired the acetylcholine-mediated increase in FBF, an effect also
      prevented by vitamin C. In contrast, hyperoxia had no effect on verapamil
      mediated increases in FBF. In CHF patients, hyperoxia did not affect FBF
      responses to acetylcholine or verapamil. The addition of vitamin C during
      hyperoxia augmented FBF responses to acetylcholine. These results suggest that
      hyperoxic vasoconstriction is mediated by oxidative stress. Moreover, hyperoxia
      impairs acetylcholine-mediated vasodilation in the setting of intact endothelial
      function. These effects of hyperoxia are prevented by vitamin C, providing
      evidence that hyperoxia-derived free radicals impair the activity of endothelium
      derived vasoactive factors.

PMID- 12003854
TI  - Differential response to myocardial reperfusion injury in eNOS-deficient mice.
AB  - Two strains of endothelial nitric oxide synthase (eNOS)-deficient (-/-) mice have
      been developed that respond differently to myocardial ischemia-reperfusion
      (MI/R). We evaluated both strains of eNOS(-/-) mice in an in vivo model of MI/R.
      Harvard (Har) eNOS(-/-) mice (n = 12) experienced an 84% increase in myocardial
      necrosis compared with wild-type controls (P < 0.05). University of North
      Carolina (UNC) eNOS(-/-) (n = 10) exhibited a 52% reduction in myocardial injury
      versus wild-type controls (P < 0.05). PCR analysis of myocardial inducible NO
      synthase (iNOS) mRNA levels revealed a significant (P < 0.05) increase in the UNC
      eNOS(-/-) mice compared with wild-type mice, and there was no significant
      difference between the Har eNOS(-/-) and wild-type mice. UNC eNOS(-/-) mice
      treated with an iNOS inhibitor (1400W) exacerbated the extent of myocardial
      necrosis. When treated with 1400W, Har eNOS(-/-) did not exhibit a significant
      increase in myocardial necrosis. These data demonstrate that two distinct strains
      of eNOS(-/-) mice display opposite responses to MI/R. Although the protection
      seen in the UNC eNOS(-/-) mouse may result from compensatory increases in iNOS,
      other genes may be involved.

PMID- 12003855
TI  - Mechanics of the human femoral adventitia including the high-pressure response.
AB  - Adventitial mechanics were studied on the basis of adventitial tube tests and
      associated stress analyses utilizing a thin-walled model. Inflation tests of 11
      nonstenotic human femoral arteries (79.3 +/- 8.2 yr, means +/- SD) were performed
      during autopsy. Adventitial tubes were separated anatomically and underwent
      cyclic, quasistatic extension-inflation tests using physiological pressures and
      high pressures up to 100 kPa. Associated circumferential and axial stretches were
      typically <20%, indicating "adventitiosclerosis." Adventitias behaved nearly
      elastically for both loading domains, demonstrating high tensile strengths (>1
      MPa). The anisotropic and strongly nonlinear mechanical responses were
      represented appropriately by two-dimensional Fung-type stored-energy functions.
      At physiological pressure (13.3 kPa), adventitias carry ~25% of the pressure load
      in situ, whereas their circumferential and axial stresses were similar to the
      total wall stresses (~50 kPa in both directions), supporting a "uniform stress
      hypothesis." At higher pressures, they became the mechanically predominant layer,
      carrying >50% of the pressure load. These significant load-carrying capabilities
      depended strongly on circumferential and axial in-vessel prestretches (mean
      values: 0.95 and 1.08). On the basis of these results, the mechanical role of the
      adventitia at physiological and hypertensive states and during balloon
      angioplasty was characterized.

PMID- 12003856
TI  - Aware or unaware: assessment of cortical blindness in four men and a monkey.
AB  - In four patients and one monkey with unilateral visual field defects caused by
      retro-geniculate lesions we measured forced-choice localization of square-wave
      gratings as a function of contrast, and compared results from the patients'
      absolutely and relatively blind fields. In addition, the patients indicated
      verbally whether they were aware of the stimuli. We then switched to a signal
      detection task in which the subjects had to signal a stimulus as in the
      localization task, by touching it, no matter whether it appeared in the good or
      bad hemifield, and in addition to signal a blank trial by touching an outlined
      square now constantly present on the monitor, and designated the no-stimulus
      response area. In this way, we could compare a non-verbal procedure that we had
      previously used in hemianopic monkeys with a verbal one commonly used to assess
      visual awareness. The results showed a close correspondence between the two
      measures of awareness in the human subjects who signalled 'stimulus' only for
      targets that also evoked verbal aware responses, validating the non-verbal
      approach. The hemianopic monkey behaved more like a patient with an absolute
      rather than a relative defect, and perfectly localized high-contrast stimuli
      which she nevertheless treated as blanks in the vast majority of presentations in
      the signal detection task.

PMID- 12003857
TI  - Inhibitory and excitatory responses of single neurons in the human medial
      temporal lobe during recognition of faces and objects.
AB  - The medial temporal lobe (MTL) plays a critical role in transforming complex
      stimuli into permanent memory traces, yet little is known on how the activity of
      neurons in the human brain mediates this process. Recording from single neurons
      in the human MTL during visual encoding and retrieval of faces and objects, we
      found that in the hippocampus faces evoked predominantly suppression of neuronal
      firing below prestimulus baseline ('inhibitory responses'). These responses were
      also prevalent in the entorhinal cortex but were absent in the amygdala during
      the first second of stimulus encoding when all responses to faces were
      'excitatory' (neuronal firing increased above the prestimulus baseline).
      Inhibitory responses were more prevalent during recognition than encoding and
      were also present during processing of objects, albeit less frequently than
      during processing of faces. Despite the prevalence in the hippocampus of cells
      with inhibitory responses and their relative specificity to faces, it was mainly
      the activity of the cells with excitatory responses that was selective for
      stimulus features such as gender and emotional expression of faces. These
      findings suggest that a large population of cells with inhibitory responses is
      engaged in the hippocampal memory network, but primarily cells with excitatory
      responses process feature-specific information.

PMID- 12003858
TI  - A simple and effective method for obtaining stable in vivo whole-cell recordings
      from visual cortical neurons.
AB  - We describe a simple and effective method for obtaining stable in vivo whole-cell
      recordings in cat visual cortex. The core of the new approach is to prevent brain
      pulsation by retaining the dura mater. After being treated with an enzyme
      (collagenase), the dura became soft enough to allow easy penetration by a patch
      clamp electrode with negligible damage to the tip. The procedure is as simple as
      those used for extracellular recordings, and all the intricate steps required for
      conventional techniques are no longer necessary. The reliability of this approach
      is demonstrated by stable and sustained intracellular recordings and high-quality
      intracellular staining. The method is especially effective for studying small
      neurons in the superficial layers immediately below the dura.

PMID- 12003859
TI  - Reactivation of networks involved in preparatory states.
AB  - We report an endogenous signal that has a widespread cortical distribution and is
      time-locked to the termination of a sustained state of task-readiness. In three
      event-related functional magnetic resonance imaging (fMRI) experiments, subjects
      saw an arrow cue that predicted either the direction of motion or the location of
      a subsequent test stimulus. A reactivation of the BOLD (blood oxygenation level
      dependent) signal occurred at the termination of the state of readiness in
      occipital regions that were transiently activated by the cue and in frontal
      parietal regions that maintained an attentional set over the trial. Moreover, a
      delayed activation occurred in prefrontal and temporo-parietal regions that did
      not initially respond to the cue and that have been implicated in re-orienting
      attention to novel sensory events. These latter regions may have generated
      control signals that ended the state of readiness in regions active during the
      cue period. These results indicate that terminating a state of readiness produces
      a widely distributed cortical signal and suggest that areas involved in a
      preparatory state may be maintained as a network which can be modulated as a
      whole.

PMID- 12003860
TI  - Spatial receptive field organization of macaque V4 neurons.
AB  - Subfield analysis of the receptive fields (RFs) of parafoveal V4 complex cells
      demonstrates directly that most RFs are tiled by overlapping second-order
      excitatory inputs that for any given V4 cell are predominantly selective to the
      same preferred values of spatial frequency and orientation. These results extend
      hierarchical principles of RF organization in the spatial, orientation and
      spatial frequency domains, first recognized in V1, to an intermediate
      extrastriate cortex. Spatial interaction studies across subfields demonstrate
      that the responses of V4 neurons to paired stimuli may either decrease or
      increase as a function of inter-stimulus distance across the width axis. These
      intra-RF suppressions and facilitations vary independently in magnitude and
      spatial extent from cell to cell. These results taken together with the
      relatively large RF sizes of V4 neurons - as compared with RF sizes of their
      afferent inputs - lead us to hypothesize a novel property, namely that classes of
      stimulus configurations that enhance areal summation while reducing suppressive
      interactions between excitatory inputs will evoke especially robust responses. We
      tested, and found support for, this hypothesis by presenting stimuli consisting
      of optimally tuned sine-wave gratings visible only within an annular region and
      found that such stimuli vigorously activate V4 neurons at firing rates far higher
      than those evoked by comparable stimuli to either the full-field or central core.
      On the basis of these results we propose a framework for a new class of neural
      network models for the spatial RF organizations of prototypic V4 neurons.

PMID- 12003861
TI  - PSA-NCAM immunoreactivity in chandelier cell axon terminals of the human temporal
      cortex.
AB  - In the adult central nervous system, the expression of polysialylated forms of
      the cell-surface glycoprotein NCAM (PSA-NCAM) is thought to be confined to areas
      particularly susceptible to plastic changes. In the present study, PSA-NCAM was
      found to be expressed in the somata, dendrites and axonal processes of some
      neurons, including cartridge-like elements, which according to our criteria, were
      identified as chandelier cell axon terminals (chandelier terminals), in the adult
      human entorhinal cortex and neocortex. These chandelier terminals were very
      numerous in layers II and III, whereas in deeper layers they were found only
      occasionally. Double immunocytochemical staining for PSA-NCAM with parvalbumin
      (PV), with GABA transporter (GAT-1) or with the 5-HT(1A) serotonin receptor
      allowed us to verify them as true chandelier terminals. Nearly all (92-95%) PV
      immunoreactive (-ir) and GAT-1-ir chandelier terminals in layers II and III
      coexpressed PSA-NCAM. Most of the PSA-NCAM-ir chandelier terminals (89-98%) were
      also labeled for PV and GAT-1. The results suggest that chandelier terminals in
      layers II and III of the human entorhinal cortex and temporal neocortex might be
      particularly susceptible to plastic changes.

PMID- 12003862
TI  - Differential distribution of group I metabotropic glutamate receptors during rat
      cortical development.
AB  - Neurons in the rat cerebral cortex are enriched in group I metabotropic glutamate
      receptor (mGluR) subtypes and respond to their activation during development. To
      understand better the mechanisms by which mGluR1 and mGluR5 mediate these
      effects, the goal of this study was to elucidate the expression pattern and to
      determine the cellular and the precise subcellular localization of these two
      receptor subtypes in the rat neocortex and hippocampus during late prenatal and
      postnatal development. At the light microscopic level, mGluR1alpha and mGluR5
      were first detected in the cerebral cortex with different expression levels at
      embryonic day E18. Thus, mGluR5 had a moderate expression, whereas mGluR1alpha
      was detected as a diffuse and weak labeling. mGluR5 was localized in some Cajal-
      Retzius cells as well as in other cell types, such as pioneer neurons of the
      marginal zone. During postnatal development, the distribution of the receptors
      dramatically changed. From P0 to around P10, mGluR1alpha was localized in
      identified, transient Cajal-Retzius cells of neocortex and hippocampus, until
      these cells disappear. In addition, a population of interneurons localized the
      receptor from the second/third postnatal week. In contrast, mGluR5 was localized
      mainly in pyramidal cells and in some interneurons, with a neuropilar staining
      throughout the cerebral cortex. At the electron microscopic level, the
      immunoreactivity for both group I mGluR subtypes was expressed postsynaptically.
      Using immunogold methods, mGluR1alpha and mGluR5 immunoreactivities were found
      throughout postnatal development at the edge of postsynaptic specialization of
      asymmetrical synapses. These results show that the two group I mGluRs have a
      differential expression pattern in neocortex and hippocampus that may suggest
      roles for the receptors in the early processing of cortical information and in
      the control of cortical developmental events.

PMID- 12003863
TI  - Neuronal responses to optic flow in the monkey parietal area PEc.
AB  - Area PEc, a high order association area, is located in the dorsocaudal portion of
      the superior parietal cortex. PEc neurons encode visual motion signals,
      especially the direction of stimulus motion. The present study tested if PEc
      neurons also process visual correlates of self-motion. The extracellular activity
      of single neurons in response to optic flow stimuli was recorded in two monkeys
      (Macaca fascicularis) trained in a fixation task. The stimuli were produced by
      random dots simulating planar motion, radial expansion and radial contraction. A
      substantial number of PEc neurons were specifically activated by radial optic
      flow and were selective for the position of the focus of expansion with respect
      to the fovea. Eccentric positions of the focus of expansion were preferred.
      Almost all neurons showed opponent excitatory-inhibitory activity to expanding
      contracting visual fields. Planar motion elicited very weak responses. Optic flow
      responsiveness is not entirely explained by classical bar sensitivity in PEc
      neurons, suggesting that optic flow and classical bar responses could serve
      different mechanisms in the integration of visuo-motor signals to prepare body
      movements.

PMID- 12003864
TI  - The organization of orientation selectivity throughout macaque visual cortex.
AB  - A double-label deoxyglucose technique was used to study orientation columns
      throughout visual cortex in awake behaving macaques. Four macaques were trained
      to fixate while contrastreversing, stationary gratings or one-dimensional noise
      of a single orientation or an orthogonal orientation were presented, during
      uptake of [14C]deoxyglucose ([14C]DG) or [3H]DG, respectively. The two orthogonal
      stimulus orientations produced DG-labeled columns that were maximally separated
      in the two isotope maps (inter-digitated) in four areas: V1, V2, V3 and VP. The
      topographic change from interdigitated to overlapping columns occurred abruptly
      rather than gradually, at corresponding cortical area borders (e.g. VP and V4v,
      respectively). In addition, the data suggest that orientation column topography
      systematically changes with retinotopic eccentricity. In V1, the orientation
      columns systematically avoided the cytochrome oxidase blobs in the parafoveal
      representation, but converged closer to the blobs in the foveal representation. A
      control experiment indicated that this was unlikely to reflect eccentricity
      dependent differences in cortical spatial frequency sensitivity. A similar
      eccentricity-dependent change in the topography of orientation columns occurred
      in V2. In parafoveal but not foveal visual field representations of V2, the
      orientation columns were centered on the thick cytochrome oxidase stripes,
      extended into the adjacent interstripe region, but were virtually absent in the
      thin stripes.

PMID- 12003865
TI  - Priming of motion direction and area V5/MT: a test of perceptual memory.
AB  - Presentation of supraliminal or subliminal visual stimuli that can (or cannot) be
      detected or identified can improve the probability of the same stimulus being
      detected over a subsequent period of seconds, hours or longer. The locus and
      nature of this perceptual priming effect was examined, using suprathreshold
      stimuli, in subjects who received repetitive pulse transcranial magnetic
      stimulation over the posterior occipital cortex, the extrastriate motion area
      V5/MT or the right posterior parietal cortex during the intertrial interval of a
      visual motion direction discrimination task. Perceptual priming observed in a
      control condition was abolished when area V5/MT was stimulated but was not
      affected by magnetic stimulation over striate or parietal sites. The effect of
      transcranial magnetic stimulation (TMS) on priming was specific to site (V5/MT)
      and to task - colour priming was unaffected by TMS over V5/MT. The results
      parallel, in the motion domain, recent demonstrations of the importance of
      macaque areas V4 and TEO for priming in the colour and form domains.

PMID- 12003866
TI  - War on the roads.

PMID- 12003867
TI  - Ensuring the safety of school age passengers.

PMID- 12003868
TI  - Protecting pedestrians.

PMID- 12003869
TI  - A new deal for road crash victims.

PMID- 12003870
TI  - Flexible training under the new deal.

PMID- 12003871
TI  - Discrimination in medicine.

PMID- 12003872
TI  - Drug misuse causes major problems for women in India.

PMID- 12003873
TI  - Doctors accept $50 a time to listen to drug representatives.

PMID- 12003874
TI  - Car makers press Europe for voluntary agreement on safety.

PMID- 12003875
TI  - WMA protests at claim that it planned to expel Israeli doctors. World Medical
      Association.

PMID- 12003876
TI  - Tired surgical trainees. Sleep deprivation affects psychomotor function.

PMID- 12003877
TI  - Pill claimants accuse defendants' witness of "cavalier" attitude.

PMID- 12003878
TI  - How can road safety be improved? More people die on the roads than from malaria,
      says WHO chief.

PMID- 12003879
TI  - Poor quality data are major obstacle to improving road safety, says World Bank.

PMID- 12003880
TI  - Cyclists and pedestrians are sacrificed for the greater safety of motorists, says
      campaigner.

PMID- 12003881
TI  - Motor industry should introduce soft impact car bodies, says MP.

PMID- 12003882
TI  - Association of driver air bags with driver fatality: a matched cohort study.
AB  - OBJECTIVE: To estimate the association of driver air bag presence with driver
      fatality in road traffic crashes. DESIGN: Matched pair cohort study. SETTING: All
      passenger vehicle crashes in the United States during 1990-2000 inclusive.
      SUBJECTS: 51 031 driver-passenger pairs in the same vehicle. MAIN OUTCOME
      MEASURES: Relative risk of death within 30 days of a crash. RESULTS: Drivers with
      an air bag were less likely to die than drivers without an air bag (adjusted
      relative risk 0.92 (95% confidence interval 0.88 to 0.96)). This estimate was
      nearly the same whether drivers wore a seat belt (adjusted relative risk 0.93) or
      not (0.91). Air bags were associated with more protection for women (0.88 (0.82
      to 0.93)), than for men (0.94 (0.90 to 0.99)). Drivers wearing a seat belt were
      less likely to die than unbelted drivers (0.35 (0.33 to 0.36)). Belted drivers
      with an air bag were less likely to die than unbelted drivers without an air bag
      (0.32 (0.30 to 0.34)). CONCLUSIONS: If the associations are causal the average
      risk of driver death was reduced 8% (95% confidence interval 4% to 12%) by an air
      bag. Benefit was similar for belted and unbelted drivers and was slightly greater
      for women. However, seat belts offered much more protection than air bags.

PMID- 12003883
TI  - Are seat belt restraints as effective in school age children as in adults? A
      prospective crash study.
AB  - OBJECTIVE: To study effectiveness of seat belts for protecting school age
      children in road vehicle crashes. DESIGN: Crash examinations by trained
      investigators. SETTING: Ten Canadian university based crash investigation
      centres. SUBJECTS: 470 children aged 4-14 years, with 168 selected for detailed
      analysis, and 1301 adults. MAIN OUTCOME MEASURES: Use of seat belts by vehicle
      occupants; severity of injury adjusted for age and crash severity. RESULTS:
      Overall, 40% (189/470) of children were unbelted. Of the 335 children in cars
      driven by belted adults, 73 (22%) were unbelted. The odds of sustaining fatal or
      moderately severe injury (injury severity score > or =4) for children in the
      front passenger seat was more than nine times higher for unbelted children than
      for belted ones (odds ratio 9.8 (95% confidence interval 2.4 to 39.4)) and for
      those in the rear left seat was more than two times higher for unbelted than for
      belted children (2.6 (1.1 to 5.9)). The protection afforded by seat belts
      compared favourably with the results for adults in the same seat positions (odds
      ratios for unbelted v belted adults of 2.4 and 2.7 for front and rear seat
      passengers respectively). CONCLUSIONS: Seat belts helped to protect school age
      children from injury in road vehicle crashes. However, 40% of children were
      unbelted. Despite standard seat belts being designed for adults, school age
      children were at least as well protected as adults.

PMID- 12003884
TI  - Driver sleepiness and risk of serious injury to car occupants: population based
      case control study.
AB  - OBJECTIVES: To estimate the contribution of driver sleepiness to the causes of
      car crash injuries. DESIGN: Population based case control study. SETTING:
      Auckland region of New Zealand, April 1998 to July 1999. PARTICIPANTS: 571 car
      drivers involved in crashes where at least one occupant was admitted to hospital
      or killed ("injury crash"); 588 car drivers recruited while driving on public
      roads (controls), representative of all time spent driving in the study region
      during the study period. MAIN OUTCOME MEASURES: Relative risk for injury crash
      associated with driver characteristics related to sleep, and the population
      attributable risk for driver sleepiness. RESULTS: There was a strong association
      between measures of acute sleepiness and the risk of an injury crash. After
      adjustment for major confounders significantly increased risk was associated with
      drivers who identified themselves as sleepy (Stanford sleepiness score 4-7 v 1-3;
      odds ratio 8.2, 95% confidence interval 3.4 to 19.7); with drivers who reported
      five hours or less of sleep in the previous 24 hours compared with more than five
      hours (2.7, 1.4 to 5.4); and with driving between 2 am and 5 am compared with
      other times of day (5.6, 1.4 to 22.7). No increase in risk was associated with
      measures of chronic sleepiness. The population attributable risk for driving with
      one or more of the acute sleepiness risk factors was 19% (15% to 25%).
      CONCLUSIONS: Acute sleepiness in car drivers significantly increases the risk of
      a crash in which a car occupant is injured or killed. Reductions in road traffic
      injuries may be achieved if fewer people drive when they are sleepy or have been
      deprived of sleep or drive between 2 am and 5 am.

PMID- 12003885
TI  - Safety education of pedestrians for injury prevention: a systematic review of
      randomised controlled trials.
AB  - OBJECTIVES: To quantify the effectiveness of safety education of pedestrians.
      DESIGN: Systematic review of randomised controlled trials of safety education
      programmes for pedestrians of all ages. MAIN OUTCOME MEASURES: Effect of safety
      education on pedestrians' injuries, behaviour, attitude, and knowledge and on
      pedestrian-motor vehicle collisions. Quality of trials: methods of randomisation;
      and numbers lost to follow up. RESULTS: We identified 15 randomised controlled
      trials of safety education programmes for pedestrians. Fourteen trials targeted
      children, and one targeted institutionalised adults. None assessed the effect of
      safety education on the occurrence of pedestrian injury, but six trials assessed
      its effect on behaviour. The effect of pedestrian education on behaviour varied
      considerably across studies and outcomes. CONCLUSIONS: Pedestrian safety
      education can change observed road crossing behaviour, but whether this reduces
      the risk of pedestrian injury in road traffic crashes is unknown. There is a lack
      of good evidence of effectiveness of safety education for adult pedestrians,
      specially elderly people. None of the trials was conducted in low or middle
      income countries.

PMID- 12003886
TI  - Cross sectional survey of socioeconomic variations in severity and mechanism of
      childhood injuries in Trent 1992-7.
AB  - OBJECTIVE: To determine the relation between morbidity from injury and
      deprivation for different levels of injury severity and for different injury
      mechanisms for children aged 0-14 years. DESIGN: Cross sectional survey of
      routinely collected hospital admission data for injury 1992-7. SETTING: 862
      electoral wards in Trent Region. SUBJECTS: 21 587 injury related hospital
      admissions for children aged 0-4 years and 35 042 admissions for children aged 5
      14. MAIN OUTCOME MEASURES: Rate ratios for hospital admission for all injuries,
      all injuries involving long bone fracture, and all injuries involving long bone
      fracture requiring an operation; rate ratios for hospital admission for six types
      of injury mechanism divided by quintiles of the electoral wards' Townsend scores
      for deprivation. Rate ratios calculated by Poisson regression, with adjustment
      for distance from nearest hospital admitting patients with injuries, rurality,
      ethnicity, and percentage of males in each electoral ward. RESULTS: Both total
      number of admissions for injury and admissions for injuries of higher severity
      increased with increasing socioeconomic deprivation. These gradients were more
      marked for 0-4 year old children than 5-14 year olds. In terms of injury
      mechanisms, the steepest socioeconomic gradients (where the rate for the fifth of
      electoral wards with the highest deprivation scores was > or =3 times that of the
      fifth with the lowest scores) were for pedestrian injuries (adjusted rate ratio
      3.65 (95% confidence interval 2.94 to 4.54)), burns and scalds (adjusted rate
      ratio 3.49 (2.81 to 4.34)), and poisoning (adjusted rate ratio 2.98 (2.65 to
      3.34)). CONCLUSION: There are steep socioeconomic gradients for injury morbidity
      including the most common mechanisms of injury. This has implications for
      targeting injury prevention interventions and resources.

PMID- 12003887
TI  - Prehospital care for road traffic casualties.

PMID- 12003888
TI  - The neglected epidemic: road traffic injuries in developing countries.

PMID- 12003889
TI  - Reducing motor vehicle crash deaths and injuries in newly motorising countries.

PMID- 12003890
TI  - Designing road vehicles for pedestrian protection.

PMID- 12003891
TI  - Does risk homoeostasis theory have implications for road safety. For.

PMID- 12003892
TI  - Road traffic injuries are a global public health problem.

PMID- 12003893
TI  - Increasing visibility of speed cameras might increase deaths and injuries on
      roads.

PMID- 12003894
TI  - System of renewal of driving licences for elderly people needs overhauling.

PMID- 12003895
TI  - Tired surgical trainees. Junior doctors are not alone in getting tired:
      consultants do too.

PMID- 12003896
TI  - Controlled studies on reducing alcohol-impaired driving are being registered.

PMID- 12003897
TI  - Breast screening guidelines should be adapted in Down's syndrome.

PMID- 12003898
TI  - Researching outcomes of educational interventions. Theory based evaluation is
      interim measure of implementation.

PMID- 12003899
TI  - Standards are needed for quality of life clinical trials.

PMID- 12003900
TI  - Adherence to peak flow monitoring. Information provided by meters should be part
      of self management plan.

PMID- 12003901
TI  - Immunity conferred by smallpox vaccine. How long does immunity last?

PMID- 12003902
TI  - Over the counter cough medicines for acute cough. The fact that people keep
      buying the medicines is itself evidence.

PMID- 12003903
TI  - Playing video games seems to have few serious acute adverse effects on health.

PMID- 12003904
TI  - Compliance is limited by opposing recommendations.

PMID- 12003905
TI  - Making many small changes can result in quality improvement.

PMID- 12003906
TI  - Multicentre validation study of instrument applications for %CDT, an immunoassay
      for quantification of carbohydrate-deficient transferrin in serum.
AB  - This multicentre trial assessed the inter-laboratory transferability and
      agreement of results for five instrument applications (Immage, BN A, BN II, Cobas
      Mira and Microtiter) of the Axis-Shield %CDT kit, a new version immunoassay for
      quantification of the alcohol marker carbohydrate-deficient transferrin (CDT) in
      serum. Two %CDT kit controls and three authentic serum samples were compared by
      14 laboratories in six European countries, and each application was evaluated at
      three study sites. The %CDT results showed an overall good agreement both within
      and between sites, although it was also demonstrated that the analysis might be
      biased due to site performance. The data indicate that transferability of the
      %CDT assay is high, and that the instrument applications may be used
      interchangeably in routine quantification of %CDT.

PMID- 12003907
TI  - Cadmium turnover and changes of zinc and copper body status of rats continuously
      exposed to cadmium and ethanol.
AB  - The effects of continuous exposure to cadmium (Cd) and ethanol on Cd turnover and
      zinc (Zn) and copper (Cu) body status of male Wistar rats were studied. The
      animals received an aqueous solution of 10% (w/v) ethanol and/or 50 mg Cd/l as
      the only drinking fluid for 12 weeks. The concentrations of Zn, Cu and Cd in the
      serum (or blood), liver, kidneys, spleen, brain, heart, femoral muscle and femur
      as well as in 24-h urine and faeces specimens were assessed by atomic absorption
      spectrometry (AAS). Ethanol alone had no effect on Cd accumulation or excretion.
      By contrast, co-administration of ethanol with Cd influenced the turnover of this
      toxic metal. Long-term consumption of ethanol alone caused a decrease in femur Zn
      and liver Cu concentrations. Moreover, the urinary loss of both bioelements
      decreased, whereas their faecal excretion was increased. Exposure to Cd resulted
      in an increase in liver and kidney and in a decrease in femur and 24-h urine Zn
      concentrations. An increase in Cu concentration in the kidney and a decrease in
      the brain were also noted. Moreover, Cd increased the total pool of Zn in organs
      (kidneys, liver, spleen, heart and brain), but did not influence that of Cu. Zn
      concentration in the liver, kidney and spleen of rats co-exposed to Cd and
      ethanol were increased, but were decreased in the brain and femur, compared to
      controls. The concentrations of Cu in livers and brains of these rats were
      decreased, whereas those in kidney, spleen and heart were increased. The urinary
      excretion of the elements was decreased, whereas their faecal excretion was
      increased. Moreover, the total amount of Cu in organs decreased below the control
      value and that of Zn was in the normal range. These changes in Zn and Cu levels
      could be explained by different effects of both toxic substances, differences in
      bioelement intakes (due to reduced consumption of drinking solutions and food),
      and the modifying effect of ethanol on Cd turnover. Our results suggest that
      alcoholics may be more susceptible to Cd accumulation and its effects on body Zn
      and Cu.

PMID- 12003908
TI  - Combined calcium carbimide and ethanol treatment induces high blood acetaldehyde
      levels, myocardial apoptosis and altered expression of apoptosis-regulating genes
      in rat.
AB  - The effects of ethanol and ethanol-derived acetaldehyde on rat myocardial
      apoptosis and expression of genes involved in the regulation of apoptosis and
      cell cycle arrest were studied. Combined ethanol and calcium carbimide treatment
      for 2, 5 or 8 days (E + CC) markedly increased blood acetaldehyde levels.
      Cytosolic DNA fragmentation was quantified in the 5-day treatment group.
      Increased amount of DNA-fragmentation, reflecting increased apoptosis, was
      evident in the E + CC group (23% increase compared to controls). mRNA levels of
      genes regulating apoptosis were measured by using quantitative PCR in the 2- and
      8-day treatment groups. In the 2-day treatment group, p21 gene expression was
      increased by 25% and bax/bcl-2 mRNA ratio by 57% in E + CC, compared to the
      control, group. In the 8-day treatment group, p21 mRNA level was 24% lower, p53
      mRNA level was 15% higher (P < 0.005), and bcl-2 mRNA level 36% higher in E + CC
      treated, compared to the control, group. Interestingly, both ethanol and calcium
      carbimide treatments alone increased bax mRNA levels, as compared to the control
      group at 2 and 8 days. These results indicate that acetaldehyde might regulate
      the expression of apoptosis-linked genes and that apoptosis of myocardial cells
      may be involved in the development of alcoholic heart disease.

PMID- 12003909
TI  - Effect of chronic alcohol consumption on the ethanol- and acetaldehyde
      metabolizing systems in the rat gastrointestinal tract.
AB  - The activities of alcohol dehydrogenase (ADH), catalase, microsomal ethanol
      oxidizing system (MEOS) and aldehyde dehydrogenase (ALDH) were measured in
      gastric, small intestinal, colonic and rectal mucosal samples of rats fed on a
      liquid alcohol diet for 1 month. In the rectum and large intestine of control
      animals, the activities of ADH, MEOS and catalase were maximal, whereas the
      activity of ALDH was minimal. After chronic alcohol intoxication, MEOS activity
      increased significantly in the stomach. An activation of catalase and MEOS and a
      decrease of the low-K(M) ALDH activity were observed in the rectum of
      experimental animals. In rats consuming the alcohol diet, hypertrophy of crypts
      and an increased number of mitoses were noticed in colonic and rectal mucosa.
      Acute alcohol intoxication (2 g/kg, intragastrically) produced significantly
      higher acetaldehyde concentrations in the contents of the large intestine and
      rectum of rats receiving alcohol chronically compared to controls. Thus, after
      chronic alcohol intoxication, the large intestine regions showed a greater
      imbalance between the activities of acetaldehyde-producing and -oxidizing
      enzymes, which resulted in accumulation of acetaldehyde. This mechanism can
      account for the local toxicity of ethanol after its chronic consumption, and
      relates the development of mucosal damage and compensatory hyper-regenerative
      processes, and possibly carcinogenesis, in the colonic and rectal mucosae of
      alcoholics to the effects of acetaldehyde.

PMID- 12003910
TI  - The effects of alcohol on head injury in the motor vehicle crash victim.
AB  - The objective of this study was to determine if alcohol potentiates the severity
      of traumatic brain injury (TBI) in motor vehicle crash (MVC) victims, controlling
      for crash severity characteristics. Prior studies evaluating effects of alcohol
      on TBI have not accounted for severity of crash. We evaluated severity of head
      injury by Marshall score [a classification scale of intracranial pathology on
      head computed axial tomogram (CT)], and blood-alcohol concentration (BAC), while
      controlling for crash characteristics [traffic accident deformity score (TAD) and
      belt use]. Marshall scores were determined from initial CT or autopsy reports, by
      a neurosurgeon, and were categorized into less severe injury (<3) and more severe
      (> or =3). Logistic regression using this variable as the outcome parameter and
      crash characteristics, age and BAC as predictors was done, and the odds ratio
      (OR) and 0.95 confidence interval (0.95 CI) calculated. Fifty-eight patients were
      analysed: 41% were BAC positive, 30% had a modified Marshall score of > or =3.
      Patients with positive BAC were 2.1-fold more likely to have a more severe head
      injury as measured on CT scan by the Marshall scores. We suggest that alcohol
      potentiates severity of TBI as determined from head CT among MVC victims. Further
      research will be needed to substantiate this finding as well as to determine its
      long-term effect on clinical outcome.

PMID- 12003911
TI  - Changes in psychological symptoms during ambulant detoxification.
AB  - Reports suggest a high prevalence of psychological symptoms in alcohol-dependent
      patients, but there are difficulties in evaluating their significance. To
      elucidate these relationships, the effect of withdrawal from alcohol on
      psychological symptoms in men and women detoxifying on an ambulant basis was
      examined. A prospective study of 65 patients was carried out using a standardized
      interview which included sociodemographic indices, measures of alcohol dependence
      and problems. Psychological symptoms were measured using the General Health
      Questionnaire at three different time points. The majority of alcohol-dependent
      patients presented for treatment with co-existing psychological symptoms, but,
      for both men and women, these decreased rapidly after a 10-day detoxification
      period. For patients who remained abstinent over the next 6 weeks there was a
      further decline in psychological symptoms to almost asymptomatic levels. For
      those who resumed drinking, no such improvement was apparent. The clinical
      implication is that treatment for what may at first appear to be an independent
      co-morbid disorder may not be necessary once the patient has been withdrawn from
      alcohol and has achieved a period of abstinence.

PMID- 12003912
TI  - Alcohol use among Swedes and a psychometric evaluation of the alcohol use
      disorders identification test.
AB  - The Alcohol Use Disorders Identification Test (AUDIT) was completed by 997
      persons randomly selected from the general Swedish population (80% response
      rate). Eighteen per cent of the men and 5% of the women had hazardous or harmful
      alcohol use according to the > or =8 score criterion. AUDIT scores decreased with
      increasing age in both genders. Women are more sensitive to alcohol than men and
      when the cut-off score was set to > or =6, the female prevalence of hazardous or
      harmful alcohol use increased to nearly 11%. The 'binge drinking' question
      explained half of the total AUDIT variance and is thus the best item indicator of
      hazardous or harmful alcohol use in the test. Confirmatory and exploratory factor
      analyses revealed two AUDIT basic factors, the first three items defining a
      'hazardous consumption' factor and the other seven items an 'alcohol-related
      problems' factor. Both the internal and test- retest reliability of the Swedish
      version of AUDIT were satisfactory. A table for converting raw scores to non
      normalized T-scores for each combination of gender and three age intervals is
      presented.

PMID- 12003913
TI  - Effects of alcohol consumption on eight circulating markers of liver fibrosis.
AB  - A number of circulating breakdown products of collagen or other components of
      extracellular matrix, matrix degrading metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs) have been proposed as markers of hepatic fibrosis. However,
      the published results lack consistency. Since many of the patients with fibrosis
      studied were alcoholics, the question was raised whether recent alcohol
      consumption may affect the results obtained. Using sandwich-type assays of
      radioimmunoassay technology with corresponding antibodies, we studied eight
      markers of liver fibrosis: laminin, tenascin, undulin, TIMP-1, collagen VI,
      procollagen type III (PIIINP), hyaluronic acid (HA) and MMP-2. A group of 10
      alcoholics was studied after significant alcohol consumption and following 2
      weeks of abstinence, verified with repeated breath alcohol measurement. Laminin
      was significantly reduced at 1 week (22%) and at 2 weeks (30%). Similarly,
      tenascin and undulin were also significantly decreased. By contrast, TIMP-1,
      collagen VI, PIIINP, HA and MMP-2 did not significantly change. The mode of
      action of alcohol on these tests is unknown. These differences must be considered
      when using those measurements to assess liver fibrosis.

PMID- 12003914
TI  - Non-response bias in a sample survey on alcohol consumption.
AB  - In a non-response follow-up study, non-respondents of the original mailed
      questionnaire were approached again by house visits in order to compare their
      alcohol consumption with that of the respondents of the same mailed
      questionnaire. Differences in alcohol consumption between respondents and non
      respondents were found. There is strong evidence for overrepresentation of non
      response among abstainers, but weak evidence among frequent excessive drinkers.

PMID- 12003915
TI  - Screening for alcohol use disorders and at-risk drinking in the general
      population: psychometric performance of three questionnaires.
AB  - Most screening questionnaires are developed in clinical settings and there are
      few data on their performance in the general population. This study provides data
      on the area under the receiver-operating characteristic (ROC) curve, sensitivity,
      specificity, and internal consistency of the Alcohol Use Disorders Identification
      Test (AUDIT), the consumption questions of the AUDIT (AUDIT-C) and the Lubeck
      Alcohol Dependence and Abuse Screening Test (LAST) among current drinkers (n =
      3551) of a general population sample in northern Germany. Alcohol dependence and
      misuse according to DSM-IV and at-risk drinking served as gold standards to
      assess sensitivity and specificity and were assessed with the Munich-Composite
      Diagnostic Interview (M-CIDI). AUDIT and LAST showed insufficient sensitivity for
      at-risk drinking and alcohol misuse using standard cut-off scores, but
      satisfactory detection rates for alcohol dependence. The AUDIT-C showed low
      specificity in all criterion groups with standard cut-off. Adjusted cut-points
      are recommended. Among a subsample of individuals with previous general hospital
      admission in the last year, all questionnaires showed higher internal consistency
      suggesting lower reliability in non-clinical samples. In logistic regression
      analyses, having had a hospital admission increased the sensitivity in detecting
      any criterion group of the LAST, and the number of recent general practice visits
      increased the sensitivity of the AUDIT in detecting alcohol misuse. Women showed
      lower scores and larger areas under the ROC curves. It is concluded that setting
      specific instruments (e.g. primary care or general population) or adjusted cut
      offs should be used.

PMID- 12003916
TI  - Subjective ratings of prospective memory deficits in chronic heavy alcohol users.
AB  - Chronic alcohol abuse has a detrimental effect on retrospective memory. Less is
      known about its putative effects on everyday memory. This study looked at self
      ratings of prospective memory (PM) (memory for future events). After controlling
      for other drug and strategy use, chronic heavy alcohol users showed global
      impairments in PM, when compared to matched controls. The underlying mechanisms
      are discussed.

PMID- 12003917
TI  - Monoamine oxidase-B activity in alcohol withdrawal of smokers: is there any
      relationship with aggressiveness?
AB  - There is a considerable inconsistency in terms of the association between
      alcoholism and alterations in monoamine oxidase (MAO) activity. The main
      objectives of this study were to investigate the changes in platelet MAO-B
      activity throughout the alcohol withdrawal period and whether or not MAO-B
      activity differed between patients with high- and low-aggression tendency. We
      assayed platelet MAO-B levels spectrophotometrically in 22 male inpatients with
      alcohol dependence in their first and fourth weeks of withdrawal and in 20
      healthy controls. Patients were divided into two high- and low-aggression
      subgroups according to scores obtained in a Brown-Goodwin Assessment for Life
      History of Aggression. Our data revealed that the significantly lower platelet
      MAO-B activity observed during the first week of alcohol withdrawal in patients,
      compared to controls, did not continue in the fourth week, and that there was no
      relationship between aggressiveness and MAO activity. These results suggest that
      low platelet MAO activity may be a state marker of alcohol withdrawal period or a
      result of high alcohol consumption rather than a trait marker of alcoholism.

PMID- 12003918
TI  - Unplanned versus planned discharges from in-patient alcohol detoxification:
      retrospective analysis of 470 first-episode admissions.
AB  - Failure to complete treatment during alcohol detoxification is a major
      complication of effective clinical management. We determined the socio
      demographic characteristics, the pattern of alcohol and drug use, the hepatitis C
      status and the psychiatric state of these patients, using retrospective data on
      470 first admissions to a specialist alcohol in-patient unit. The 316 patients
      (67.2%) who had a planned discharge (PD group) were compared with the 154
      patients (32.8%) who had unplanned discharges (UPD group). Patients in the UPD
      group were younger on admission, had higher Alcohol Problems Questionnaire
      scores, had started to drink heavily at a younger age, were more likely to have
      previously used cocaine, amphetamines and heroin, and to have smoked cannabis in
      the 30 days prior to admission. They were more likely to be positive for markers
      of hepatitis C infection, to have a borderline personality disorder, antisocial
      personality disorder, or to have concurrent opiate or benzodiazepine dependence.
      PD was associated with depressive disorder. Early identification can be made of
      alcohol-dependent individuals at risk of premature drop-out during in-patient
      treatment. Interventions to retain patients at risk of premature UPD should be
      developed.

PMID- 12003919
TI  - Self-reported alcohol consumption and association to carbohydrate-deficient
      transferrin and gamma-glutamyltransferase in a random sample of the general
      population in the Republic of Karelia, Russia and in North Karelia, Finland.
AB  - In the present study, alcohol consumption was estimated in a population survey in
      Pitkaranta in the Republic of Karelia, Russia (RUS) and in the neighbouring
      province of North Karelia in Finland (FIN) in the spring of 1997 in connection
      with the National FINRISK Study. Alcohol consumption was evaluated by self-report
      and by the biological markers carbohydrate-deficient transferrin (CDT) and gamma
      glutamyltransferase (GGT). In RUS, elevated CDT values were observed in 36.6% of
      the men and 17.6% of the women. In FIN, the respective rates were 9.6% and 9.4%,
      which are similar to average European rates. The prevalence of elevated CDT
      values seen in RUS is the highest prevalence ever reported in general population
      surveys. However, the self-reported alcohol consumption was similar in the two
      regions. These results suggest that alcohol consumption especially in Russia may
      not be reliably estimated by self-reporting, and that alcohol consumption is
      relatively high, especially among men, in RUS.

PMID- 12003920
TI  - At-risk drinking among patients in an occupational medicine clinic.
AB  - This study described the prevalence and characteristics of at-risk drinkers among
      adults receiving care at an urban occupational medicine clinic. Comparisons were
      also made between occupational medicine and primary care patients. Among
      occupational medicine patients, prevalences were: 11% at-risk drinking; 51% light
      moderate drinking; 38% abstinence. Abstainers differed from alcohol users with
      regard to race (fewer Caucasian) and marijuana use (lower rates). Compared to
      light-moderate drinkers, at-risk drinkers were more likely to be smokers.
      Compared to a primary care sample, non-at-risk drinkers in occupational medicine
      reported poorer health, more activity limitations, higher rates of smoking and
      more stress and depressive symptoms. In contrast, at-risk drinkers in
      occupational medicine were quite similar to those in primary care. Occupational
      medicine clinics are viable settings in which to screen for at-risk drinking
      patterns and to implement primary and secondary prevention strategies.

PMID- 12003921
TI  - Wernicke's encephalopathy presenting with severe dysphagia: a case report.
AB  - A 62-year-old man developed dysphagia 4 weeks before the classic symptoms and
      signs of Wernicke's encephalopathy appeared. Adequate treatment with parenteral
      thiamine resulted in complete recovery of all symptoms, including his dysphagia.
      This extraordinary presentation with dysphagia, and the unusual course of the
      disease, encouraged us to present this case history.

PMID- 12003922
TI  - Alcohol use in adolescents from northern Russia: the role of the social context.
AB  - Drinking alcohol is an essential and commonplace part of life in Russia. Alcohol
      related problems in the general population and among adolescents in particular
      has become a major public health concern. The problem cannot be solely explained
      by the frequency and quantity of alcohol consumption. The social determinants of
      drinking alcohol also need to be considered. These are the focus of the present
      investigation. The social determinants of drinking behaviour were assessed by
      self-reports (Social Context of Drinking Scale, Adolescent Alcohol Involvement
      Scale and Rutgers Alcohol Problem Index) in 387 secondary school students in
      Arkhangelsk, Russia. The factor structure for the Social Context of Drinking
      Scale was similar to that noted in respect of the original study [Thombs and Beck
      (1994) Health Education and Research 9, 13-22]. Significant gender differences in
      problem drinking and the social contexts of drinking were found. High intensity
      girl drinkers were likely to drink in most social contexts, whereas high
      intensity drinking boys were more likely to drink in the context of Stress
      Control. Furthermore, boy problem drinkers were more likely to drink in the
      context of School Defiance and Peer Acceptance, whereas girl problem drinkers
      tended to drink in the contexts of School Defiance and Stress Control. In
      general, the Social Context of Drinking Scale demonstrated a good ability to
      discriminate high from low intensity drinkers, and high from low problem
      drinkers. These results may provide useful information for targeted prevention
      programmes for adolescents.

PMID- 12003923
TI  - Evolving insights: symbiosis islands and horizontal gene transfer.

PMID- 12003924
TI  - Nucleotide and amino acid sequences of oriT-traM-traJ-traY-traA-traL regions and
      mobilization of virulence plasmids of Salmonella enterica serovars enteritidis,
      gallinarum-pullorum, and typhimurium.
AB  - The virulence plasmid of Salmonella enterica serovar Gallinarum-Pullorum (pSPV)
      but not those of Salmonella enterica serovars Enteritidis (pSEV) and Typhimurium
      (pSTV) can be readily mobilized by an F or F-like conjugative plasmid. To
      investigate the reason for the difference, the oriT-traM-traJ-traY-traA-traL
      regions of the three salmonella virulence plasmids (pSVs) were cloned and their
      nucleotide and deduced amino acid sequences were examined. The cloned fragments
      were generally mobilized more readily than the corresponding full-length pSVs,
      but the recombinant plasmid containing the oriT of pSPV was, as expected, more
      readily mobilized, with up to 100-fold higher frequency than the recombinant
      plasmids containing the oriT of the other two pSVs. The nucleotide sequences of
      the oriT-traM-traJ-traY-traA-traL region of pSEV and pSTV were almost identical
      (only 4 bp differences), but differed from that of pSPV. Major nucleotide
      sequence variations were found in traJ, traY, and the Tra protein binding sites
      sby and sbm. sby of pSPV showed higher similarity than that of pSEV or pSTV to
      that of the F plasmid. The reverse was true for sbm: similarity was higher with
      pSEV and pSTV than with pSPV. In the deduced amino acid sequences of the five Tra
      proteins, major differences were found in TraY: pSEV's TraY was 75 amino acids,
      pSTV's was 106 amino acids, and pSPV's was 133 amino acids; and there were
      duplicate consensus betaalphaalpha fragments in the TraY of pSPV and F plasmid,
      whereas there was only a single betaalphaalpha fragment in that of pSEV and pSTV.

PMID- 12003925
TI  - The PtlE protein of Bordetella pertussis has peptidoglycanase activity required
      for Ptl-mediated pertussis toxin secretion.
AB  - Pertussis toxin of Bordetella pertussis is secreted by a type IV secretion system
      comprised of the products of the nine ptl (pertussis toxin liberation) genes.
      These proteins are believed to form a complex spanning both the inner and outer
      membranes and passing through the peptidoglycan layer. Peptidoglycan acts as a
      barrier for transport through the periplasm of large folded molecules. Assembled
      pertussis toxin and the secretion component proteins PtlC through PtlH are too
      large to diffuse through intact peptidoglycan. Therefore, we hypothesized that
      the Ptl system contains a peptidoglycanase activity. The PtlE protein was found
      to exhibit a sequence match to the active site of glycohydrolase enzymes. An N
      terminally polyhistidine-tagged PtlE fusion protein, constructed and expressed in
      Escherichia coli and in B. pertussis, exhibited peptidoglycanase activity on
      activity gels. A fusion protein with alanine substitutions at the putative active
      site residues (aspartic acid at position 53 and glutamic acid at position 62)
      lacked peptidoglycanase activity. B. pertussis strains with the amino acid
      substitutions were deficient for pertussis toxin secretion. Based on these
      results, we concluded that PtlE is a peptidoglycanase responsible for the local
      removal or rearrangement of the peptidoglycan layer during Ptl secretion complex
      assembly.

PMID- 12003926
TI  - Salt-dependent expression of glucosylglycerol-phosphate synthase, involved in
      osmolyte synthesis in the cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - The cyanobacterium Synechocystis sp. strain PCC 6803 is able to acclimate to
      levels of salinity ranging from freshwater to twice the seawater concentrations
      of salt by accumulating the compatible solute glucosylglycerol (GG). Expression
      of the ggpS gene coding for the key enzyme (glucosylglycerol-phosphate synthase)
      in GG synthesis was examined in detail. Under control conditions, the GgpS
      protein is stable, so that weak constitutive transcription of the ggpS gene
      resulted in a significant protein content. However, the enzyme activity was
      biochemically switched off, and no GG was detectable. After a salt shock, an
      immediate increase in mRNA content proportional to the salt content occurred,
      while the GgpS protein and GG contents rose in a linear manner. Furthermore, the
      stability of the ggpS mRNA increased transiently. In salt-acclimated cells
      expression of the ggpS gene, the GgpS protein content, and the amount of
      accumulated GG depended linearly on the external salt concentration. Mapping of
      the 5' end of the ggpS transcript revealed a long nontranslated 5' sequence and a
      putative typical cyanobacterial promoter, which did not show any obvious salt
      regulatory element. The alternative sigma factor sigma(F) was found to be
      involved in salt-dependent regulation of ggpS, since in a sigma(F) mutant
      induction of this gene was strongly reduced. The present study demonstrated that
      in addition to biochemical regulation of GgpS activity, alterations of ggpS
      expression are involved in regulation of GG synthesis in Synechocystis sp. strain
      PCC 6803. A model showing the interaction of the two regulatory levels is
      presented.

PMID- 12003927
TI  - Intramolecular regulation of the opposing (p)ppGpp catalytic activities of
      Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis.
AB  - Catalytic and regulatory domains of the Rel/Spo homolog of Streptococcus
      equisimilis affecting (p)ppGpp synthesis and degradation activities have been
      defined, and opposing activities of the purified protein and its fragments have
      been compared. Two major domains of the 739-residue Rel(Seq) protein are defined
      by limited proteolytic digestion. In vitro assays of the purified N-terminal half
      protein reveal synthesis of (p)ppGpp by an ATP-GTP 3'-pyrophosphotransferase as
      well as an ability to degrade (p)ppGpp by a Mn(2+)-dependent 3'
      pyrophosphohydrolase. Removal of the C-terminal half-protein has reciprocal
      regulatory effects on the activities of the N-terminal half-protein. Compared to
      the full-length protein, deletion activates (p)ppGpp synthesis specific activity
      about 12-fold and simultaneously inhibits (p)ppGpp degradation specific activity
      about 150-fold to shift the balance of the two activities in favor of synthesis.
      Cellular (p)ppGpp accumulation behavior is consistent with these changes. The
      bifunctional N-terminal half-protein can be further dissected into overlapping
      monofunctional subdomains, since purified peptides display either degradation
      activity (residues 1 to 224) or synthetic activity (residues 79 to 385) in vitro.
      These assignments can also apply to RelA and SpoT. The ability of Rel(Seq) to
      mediate (p)ppGpp accumulation during amino acid starvation in S. equisimilis is
      absent when the protein is expressed ectopically in Escherichia coli. Fusing the
      N-terminal half of Rel(Seq) with the C-terminal domain of RelA creates a chimeric
      protein that restores the stringent response in E. coli by inhibiting unregulated
      degradation and restoring regulated synthetic activity. Reciprocal intramolecular
      regulation of the dual activities may be a general intrinsic feature of Rel/Spo
      homolog proteins.

PMID- 12003928
TI  - Identification of a lycopene beta-cyclase required for bacteriorhodopsin
      biogenesis in the archaeon Halobacterium salinarum.
AB  - Biogenesis of the light-driven proton pump bacteriorhodopsin in the archaeon
      Halobacterium salinarum requires coordinate synthesis of the bacterioopsin
      apoprotein and carotenoid precursors of retinal, which serves as a covalently
      bound cofactor. As a step towards elucidating the mechanism and regulation of
      carotenoid metabolism during bacteriorhodopsin biogenesis, we have identified an
      H. salinarum gene required for conversion of lycopene to beta-carotene, a retinal
      precursor. The gene, designated crtY, is predicted to encode an integral membrane
      protein homologous to lycopene beta-cyclases identified in bacteria and fungi. To
      test crtY function, we constructed H. salinarum strains with in-frame deletions
      in the gene. In the deletion strains, bacteriorhodopsin, retinal, and beta
      carotene were undetectable, whereas lycopene accumulated to high levels (
      approximately 1.3 nmol/mg of total cell protein). Heterologous expression of H.
      salinarum crtY in a lycopene-producing Escherichia coli strain resulted in beta
      carotene production. These results indicate that H. salinarum crtY encodes a
      functional lycopene beta-cyclase required for bacteriorhodopsin biogenesis.
      Comparative sequence analysis yields a topological model of the protein and
      provides a plausible evolutionary connection between heterodimeric lycopene
      cyclases in bacteria and bifunctional lycopene cyclase-phytoene synthases in
      fungi.

PMID- 12003929
TI  - Alcohol-induced delay of viability loss in stationary-phase cultures of
      Escherichia coli.
AB  - During prolonged incubation in stationary phase Escherichia coli undergoes
      starvation-induced differentiation, resulting in highly resistant cells. In rich
      medium with high amino acid content further incubation of cultures at high cell
      density leads to the generation of a population of cells no longer able to form
      colonies. The viability loss is due to some component of spent medium, active at
      high pH and high cell density, and can be prevented either by keeping the pH
      close to neutrality, by washing off the nonsalt components of the medium, or by
      keeping the saturating cell density low. Exposure to short-chain n-alcohols
      within a specific time window in stationary phase also prevents viability loss,
      in an rpoS-dependent fashion. The development of stress resistance, a hallmark of
      stationary-phase cells, is affected following alcohol treatment, as is the
      response to extracellular factors in spent medium. Alcohols seem to block cells
      in an early phase of starvation-induced differentiation, most likely by
      interfering with processes important for regulation of sigma(s) such as cell
      density signals and sensing the nutrient content of the medium.

PMID- 12003930
TI  - Plasmid-encoded asp operon confers a proton motive metabolic cycle catalyzed by
      an aspartate-alanine exchange reaction.
AB  - Tetragenococcus halophila D10 catalyzes the decarboxylation of L-aspartate with
      nearly stoichiometric release of L-alanine and CO(2). This trait is encoded on a
      25-kb plasmid, pD1. We found in this plasmid a putative asp operon consisting of
      two genes, which we designated aspD and aspT, encoding an L-aspartate-beta
      decarboxylase (AspD) and an aspartate-alanine antiporter (AspT), respectively,
      and determined the nucleotide sequences. The sequence analysis revealed that the
      genes of the asp operon in pD1 were in the following order: promoter --> aspD -->
      aspT. The deduced amino acid sequence of AspD showed similarity to the sequences
      of two known L-aspartate-beta-decarboxylases from Pseudomonas dacunhae and
      Alcaligenes faecalis. Hydropathy analyses suggested that the aspT gene product
      encodes a hydrophobic protein with multiple membrane-spanning regions. The operon
      was subcloned into the Escherichia coli expression vector pTrc99A, and the two
      genes were cotranscribed in the resulting plasmid, pTrcAsp. Expression of the asp
      operon in E. coli coincided with appearance of the capacity to catalyze the
      decarboxylation of aspartate to alanine. Histidine-tagged AspD (AspDHis) was also
      expressed in E. coli and purified from cell extracts. The purified AspDHis
      clearly exhibited activity of L-aspartate-beta-decarboxylase. Recombinant AspT
      was solubilized from E. coli membranes and reconstituted in proteoliposomes. The
      reconstituted AspT catalyzed self-exchange of aspartate and electrogenic
      heterologous exchange of aspartate with alanine. Thus, the asp operon confers a
      proton motive metabolic cycle consisting of the electrogenic aspartate-alanine
      antiporter and the aspartate decarboxylase, which keeps intracellular levels of
      alanine, the countersubstrate for aspartate, high.

PMID- 12003931
TI  - Identification and physical characterization of the HbpR binding sites of the
      hbpC and hbpD promoters.
AB  - Pseudomonas azelaica HBP1 can use 2-hydroxybiphenyl (2-HBP) and 2,2'
      dihydroxybiphenyl as sole carbon and energy sources by means of the hbp regulon.
      This regulon is composed of three genes, hbpCA and hbpD, coding for enzymes of a
      meta-cleavage pathway and the hbpR gene, which codes for a XylR/DmpR-type
      transcription regulator. It was previously shown that HbpR activates
      transcription from two sigma(54)-dependent promoters, P(hbpC) and P(hbpD), in the
      presence of 2-HBP. In this study, by using gel mobility shift assays with a
      purified fusion protein containing calmodulin binding protein (CBP) and HbpR, we
      detected two binding regions for HbpR in P(hbpC) and one binding region in
      P(hbpD). DNase I footprints of the proximal binding region of P(hbpC) and of the
      binding region in P(hbpD) showed that CBP-HbpR protected a region composed of two
      inverted repeat sequences which were homologous to the binding sites identified
      for XylR. Unlike the situation in the XylR/P(u) system, we observed simultaneous
      binding of CBP-HbpR on the two upstream activating sequences (UASs). Fragments
      with only one UAS did not show an interaction with HbpR, indicating that both
      pairs of UASs are needed for HbpR binding. The addition of both ATP and 2-HBP
      increased the DNA binding affinity of HbpR. These results showed for the first
      time that, for regulators of the XylR/DmpR type, the effector positively affects
      the recruitment of the regulatory protein on the enhancer DNA.

PMID- 12003932
TI  - Characterization of the HspR-mediated stress response in Helicobacter pylori.
AB  - The major heat shock genes of Helicobacter pylori are regulated by the HspR
      repressor. In the present study we characterize the transcriptional response of
      the three known HspR-dependent promoters P(cbp), P(gro), and P(hrc) to different
      environmental stresses. A temperature shift from 37 to 42 degrees C causes a
      typical heat shock response at all three promoters characterized by an immediate
      and strong induction phase of transcription and a subsequent adaptation phase,
      which is specific for each promoter and whose onset is determined partially by
      the half-lives of the respective mRNAs. Exposure to high osmolarity induces a
      similar response on the P(gro) and P(cbp) promoters while no such response is
      detectable at the P(hrc) promoter. Puromycin treatment induces transcription from
      all three HspR-dependent promoters, indicating that different environmental
      stresses are intracellularly sensed by the regulatory machinery through the
      accumulation of nonnative proteins. The implications of these data for the
      regulatory network controlling the heat shock response in H. pylori are
      discussed.

PMID- 12003933
TI  - An iron-binding protein, Dpr, from Streptococcus mutans prevents iron-dependent
      hydroxyl radical formation in vitro.
AB  - The dpr gene is an antioxidant gene which was isolated from the Streptococcus
      mutans chromosome by its ability to complement an alkyl hydroperoxide reductase
      deficient mutant of Escherichia coli, and it was proven to play an indispensable
      role in oxygen tolerance in S. mutans. Here, we purified the 20-kDa dpr gene
      product, Dpr, from a crude extract of S. mutans as an iron-binding protein and
      found that Dpr formed a spherical oligomer about 9 nm in diameter. Molecular
      weight determinations of Dpr in solution by analytical ultracentrifugation and
      light-scattering analyses gave values of 223,000 to 292,000, consistent with a
      subunit composition of 11.5 to 15 subunits per molecule. The purified Dpr
      contained iron and zinc atoms and had an ability to incorporate up to 480 iron
      and 11.2 zinc atoms per molecule. Unlike E. coli Dps and two other members of the
      Dps family, Dpr was unable to bind DNA. One hundred nanomolar Dpr prevented by
      more than 90% the formation of hydroxyl radical generated by 10 microM iron(II)
      salt in vitro. The data shown in this study indicate that Dpr may act as a
      ferritin-like iron-binding protein in S. mutans and may allow this catalase- and
      heme-peroxidase-deficient bacterium to grow under air by limiting the iron
      catalyzed Fenton reaction.

PMID- 12003934
TI  - ArgR-independent induction and ArgR-dependent superinduction of the astCADBE
      operon in Escherichia coli.
AB  - For Escherichia coli, growth in the absence of ammonia is termed nitrogen limited
      and results in the induction of genes that assimilate other nitrogen sources, a
      response mediated by sigma(54) and nitrogen regulator I (NR(I), also called
      NtrC). The astCADBE operon, which is required for growth with arginine as the
      sole nitrogen source, is moderately expressed during general nitrogen limitation
      and maximally expressed in the presence of arginine. The operon is also induced
      in stationary phase. Primer extension analysis of E. coli revealed the presence
      of a sigma(54)-dependent promoter utilized in exponential phase during nitrogen
      limitation and a sigma(S)-dependent promoter active during stationary phase. We
      used an ast-lacZ fusion to show that arginine stimulates expression, that ArgR,
      the arginine repressor, enhances expression from both promoters but is not
      essential, and that transcription by the two forms of the RNA polymerase is
      competitive and mutually exclusive. We demonstrated the binding of RNA polymerase
      holoenzymes, NR(I), and ArgR to the promoter region in vitro. We also
      reconstituted transcription from both promoters with purified components, which
      confirmed the accessory role of ArgR for the sigma(54)-dependent promoter. Thus,
      the ast operon exhibits nitrogen source-specific induction that is unique for an
      NR(I)-dependent gene. The transcriptional regulation of the ast operon in E. coli
      differs from that in Salmonella enterica serovar Typhimurium, in which ArgR is
      required for ast operon expression.

PMID- 12003935
TI  - Targeting of (D)MinC/MinD and (D)MinC/DicB complexes to septal rings in
      Escherichia coli suggests a multistep mechanism for MinC-mediated destruction of
      nascent FtsZ rings.
AB  - The MinC protein is an important determinant of septal ring positioning in
      Escherichia coli. The N-terminal domain ((Z)MinC) suppresses septal ring
      formation by interfering with FtsZ polymerization, whereas the C-terminal domain
      ((D)MinC) is required for dimerization as well as for interaction with the MinD
      protein. MinD oscillates between the membrane of both cell halves in a MinE
      dependent fashion. MinC oscillates along with MinD such that the time-integrated
      concentration of (Z)MinC at the membrane is minimal, and hence the stability of
      FtsZ polymers is maximal, at the cell center. MinC is cytoplasmic and fails to
      block FtsZ assembly in the absence of MinD, indicating that recruitment of MinC
      by MinD to the membrane enhances (Z)MinC function. Here, we present evidence that
      the binding of (D)MinC to MinD endows the MinC/MinD complex with a more specific
      affinity for a septal ring-associated target in vivo. Thus, MinD does not merely
      attract MinC to the membrane but also aids MinC in specifically binding to, or in
      close proximity to, the substrate of its (Z)MinC domain. MinC-mediated division
      inhibition can also be activated in a MinD-independent fashion by the DicB
      protein of cryptic prophage Kim. DicB shows little homology to MinD, and how it
      stimulates MinC function has been unclear. Similar to the results obtained with
      MinD, we find that DicB interacts directly with (D)MinC, that the (D)MinC/DicB
      complex has a high affinity for some septal ring target(s), and that MinC/DicB
      interferes with the assembly and/or integrity of FtsZ rings in vivo. The results
      suggest a multistep mechanism for the activation of MinC-mediated division
      inhibition by either MinD or DicB and further expand the number of properties
      that can be ascribed to the Min proteins.

PMID- 12003936
TI  - Codenitrification and denitrification are dual metabolic pathways through which
      dinitrogen evolves from nitrate in Streptomyces antibioticus.
AB  - We screened actinomycete strains for dinitrogen (N(2))-producing activity and
      discovered that Streptomyces antibioticus B-546 evolves N(2) and some nitrous
      oxide (N(2)O) from nitrate (NO(3)(-)). Most of the N(2) that evolved from the
      heavy isotope ([(15)N]NO(3)(-)) was (15)N(14)N, indicating that this nitrogen
      species consists of two atoms, one arising from NO(3)(-) and the other from
      different sources. This phenomenon is similar to codenitrification in fungi. The
      strain also evolved less, but significant, amounts of (15)N(15)N from
      [(15)N]NO(3)(-) in addition to (15)N(15)NO with concomitant cell growth. Prior to
      the production of N(2) and N(2)O, NO(3)(-) was rapidly reduced to nitrite (NO(2)(
      )) accompanied by distinct cell growth, showing that the actinomycete strain is a
      facultative anaerobe that depends on denitrification and nitrate respiration for
      anoxic growth. The cell-free activities of denitrifying enzymes could be
      reconstituted, supporting the notion that the (15)N(15)N and (15)N(15)NO species
      are produced by denitrification from NO(3)(-) via NO(2)(-). We therefore
      demonstrated a unique system in an actinomycete that produces gaseous nitrogen
      (N(2) and N(2)O) through both denitrification and codenitrification. The
      predominance of codenitrification over denitrification along with oxygen
      tolerance is the key feature of nitrate metabolism in this actinomycete.

PMID- 12003937
TI  - Biochemical, molecular, and genetic analyses of the acetone carboxylases from
      Xanthobacter autotrophicus strain Py2 and Rhodobacter capsulatus strain B10.
AB  - Acetone carboxylase is the key enzyme of bacterial acetone metabolism, catalyzing
      the condensation of acetone and CO(2) to form acetoacetate. In this study, the
      acetone carboxylase of the purple nonsulfur photosynthetic bacterium Rhodobacter
      capsulatus was purified to homogeneity and compared to that of Xanthobacter
      autotrophicus strain Py2, the only other organism from which an acetone
      carboxylase has been purified. The biochemical properties of the enzymes were
      virtually indistinguishable, with identical subunit compositions
      (alpha(2)beta(2)gamma(2) multimers of 85-, 78-, and 20-kDa subunits), reaction
      stoichiometries (CH(3)COCH(3) + CO(2) + ATP-->CH(3)COCH(2)COO(-) + H(+) + AMP +
      2P(i)), and kinetic properties (K(m) for acetone, 8 microM; k(cat) = 45 min(-1)).
      Both enzymes were expressed to high levels (17 to 25% of soluble protein) in
      cells grown with acetone as the carbon source but were not present at detectable
      levels in cells grown with other carbon sources. The genes encoding the acetone
      carboxylase subunits were identified by transposon mutagenesis of X.
      autotrophicus and sequence analysis of the R. capsulatus genome and were found to
      be clustered in similar operons consisting of the genes acxA (beta subunit), acxB
      (alpha subunit), and acxC (gamma subunit). Transposon mutagenesis of X.
      autotrophicus revealed a requirement of sigma(54) and a sigma(54)-dependent
      transcriptional activator (AcxR) for acetone-dependent growth and acetone
      carboxylase gene expression. A potential sigma(54)-dependent promoter 122 bp
      upstream of X. autotrophicus acxABC was identified. An AcxR gene homolog was
      identified 127 bp upstream of acxA in R. capsulatus, but this activator lacked
      key features of sigma(54)-dependent activators, and the associated acxABC lacked
      an apparent sigma(54)-dependent promoter, suggesting that sigma(54) is not
      required for expression of acxABC in R. capsulatus. These studies reveal a
      conserved strategy of ATP-dependent acetone carboxylation and the involvement of
      transcriptional enhancers in acetone carboxylase gene expression in gram-negative
      acetone-utilizing bacteria.

PMID- 12003938
TI  - Redundancy in periplasmic binding protein-dependent transport systems for
      trehalose, sucrose, and maltose in Sinorhizobium meliloti.
AB  - We have identified a cluster of six genes involved in trehalose transport and
      utilization (thu) in Sinorhizobium meliloti. Four of these genes, thuE, -F, -G,
      and -K, were found to encode components of a binding protein-dependent
      trehalose/maltose/sucrose ABC transporter. Their deduced gene products comprise a
      trehalose/maltose-binding protein (ThuE), two integral membrane proteins (ThuF
      and ThuG), and an ATP-binding protein (ThuK). In addition, a putative regulatory
      protein (ThuR) was found divergently transcribed from the thuEFGK operon. When
      the thuE locus was inactivated by gene replacement, the resulting S. meliloti
      strain was impaired in its ability to grow on trehalose, and a significant
      retardation in growth was seen on maltose as well. The wild type and the thuE
      mutant were indistinguishable for growth on glucose and sucrose. This suggested a
      possible overlap in function of the thuEFGK operon with the aglEFGAK operon,
      which was identified as a binding protein-dependent ATP-binding transport system
      for sucrose, maltose, and trehalose. The K(m)s for trehalose transport were 8 +/-
      1 nM and 55 +/- 5 nM in the uninduced and induced cultures, respectively.
      Transport and growth experiments using mutants impaired in either or both of
      these transport systems show that these systems form the major transport systems
      for trehalose, maltose, and sucrose. By using a thuE'-lacZ fusion, we show that
      thuE is induced only by trehalose and not by cellobiose, glucose, maltopentaose,
      maltose, mannitol, or sucrose, suggesting that the thuEFGK system is primarily
      targeted toward trehalose. The aglEFGAK operon, on the other hand, is induced
      primarily by sucrose and to a lesser extent by trehalose. Tests for root
      colonization, nodulation, and nitrogen fixation suggest that uptake of
      disaccharides can be critical for colonization of alfalfa roots but is not
      important for nodulation and nitrogen fixation per se.

PMID- 12003939
TI  - Nitric oxide metabolism in Neisseria meningitidis.
AB  - Neisseria meningitidis, the causative agent of meningococcal disease in humans,
      is likely to be exposed to nitrosative stress during natural colonization and
      disease. The genome of N. meningitidis includes the genes aniA and norB,
      predicted to encode nitrite reductase and nitric oxide (NO) reductase,
      respectively. These gene products should allow the bacterium to denitrify nitrite
      to nitrous oxide. We show that N. meningitidis can support growth
      microaerobically by the denitrification of nitrite via NO and that norB is
      required for anaerobic growth with nitrite. NorB and, to a lesser extent, the
      cycP gene product cytochrome c' are able to counteract toxicity due to
      exogenously added NO. Expression of these genes by N. meningitidis during
      colonization and disease may confer protection against exogenous or endogenous
      nitrosative stress.

PMID- 12003940
TI  - Sugar transport through maltoporin of Escherichia coli: role of the greasy slide.
AB  - The lining of the maltodextrin-specific maltoporin (LamB) channel exhibits a
      string of aromatic residues, the greasy slide, part of which has been shown
      previously by crystallography to be involved in substrate binding. To probe the
      functional role of the greasy slide, alanine scanning mutagenesis has been
      performed on the six greasy slide residues and Y118 at the channel constriction.
      The mutants were characterized by an in vivo uptake assay and sugar-induced
      current-noise analysis. Crystallographic analysis of the W74A mutant showed no
      perturbation of the structure. All mutants showed considerably decreased maltose
      uptake rates in vivo (<10% of the wild-type value), indicating the functional
      importance of the investigated residues. Substitutions at the channel center
      revealed appreciably increased (up to 100-fold) in vitro half-saturation
      concentrations for maltotriose and maltohexaose binding to the channel. Sugar
      association rates, however, were significantly affected also by the mutations at
      either end of the slide (W74A, W358A, and F227A), an effect which became most
      apparent upon nonsymmetrical sugar addition. The kinetic data are discussed on
      the basis of an asymmetric one-site two-barrier model, which suggests that, at
      low substrate concentrations, as are found under physiological conditions, only
      the heights of the extracellular and periplasmic barriers, which are reduced by
      the presence of the greasy slide, determine the efficiency of this facilitated
      diffusion channel.

PMID- 12003941
TI  - Mutant analysis and cellular localization of the AlgI, AlgJ, and AlgF proteins
      required for O acetylation of alginate in Pseudomonas aeruginosa.
AB  - Alginate is an extracellular polysaccharide produced by mucoid strains of
      Pseudomonas aeruginosa that are typically isolated from the pulmonary tracts of
      chronically infected cystic fibrosis patients. Alginate is a linear polymer of D
      mannuronate and L-guluronate with O-acetyl ester linkages on the O-2 and/or O-3
      position of the mannuronate residues. The presence of O-acetyl groups plays an
      important role in the ability of the polymer to act as a virulence factor, and
      the algF, algJ, and algI genes are known to be essential for the addition of O
      acetyl groups to alginate. To better understand the mechanism of O acetylation of
      alginate, the cellular locations of the AlgI, AlgJ, and AlgF proteins were
      determined. For these studies, defined nonpolar algI, algJ, and algF deletion
      mutants of P. aeruginosa strain FRD1 were constructed, and each mutant produced
      alginate lacking O-acetyl groups. Expression of algI, algJ, or algF in trans in
      the corresponding mutant complemented each O acetylation defect. Random phoA
      (alkaline phosphatase [AP] gene) fusions to algF, algJ, and algI were
      constructed. All in-frame fusions to algF and algJ had AP activity, indicating
      that both AlgF and AlgJ were exported to the periplasm. Immunoblot analysis of
      spheroplasts and periplasmic fractions showed that AlgF was released with the
      periplasmic contents but that AlgJ remained with the spheroplast fraction. An N
      terminal sequence analysis of AlgJ showed that its putative AlgJ signal peptide
      was not cleaved, suggesting that AlgJ is anchored to the cytoplasmic membrane by
      its uncleaved signal peptide. AP gene fusions were also used to map the membrane
      topology of AlgI, and the results suggest that it is an integral membrane protein
      with seven transmembrane domains. These results suggest that AlgI-AlgJ-AlgF may
      form a complex in the membrane that is the reaction center for O acetylation of
      alginate.

PMID- 12003942
TI  - Characterization of interactions between the transcriptional repressor PhlF and
      its binding site at the phlA promoter in Pseudomonas fluorescens F113.
AB  - The phlACBD genes responsible for the biosynthesis of the antifungal metabolite
      2,4-diacetylphloroglucinol (PHL) by the biocontrol strain Pseudomonas fluorescens
      F113 are regulated at the transcriptional level by the pathway-specific repressor
      PhlF. Strong evidence suggests that this regulation occurs mainly in the early
      logarithmic phase of growth. First, the expression of the phlF gene is relatively
      high between 3 and 13 h of growth and relatively low thereafter, with the phlACBD
      operon following an opposite expression profile. Second, the kinetics of PHL
      biosynthesis are specifically altered in the logarithmic phase in a P.
      fluorescens F113 phlF mutant. The phlA-phlF intergenic region presents a complex
      organization in that phlACBD is transcribed from a sigma(70) RNA polymerase
      dependent promoter that is likely to overlap the promoter of the divergently
      transcribed phlF gene. The repression by PhlF is due to its interaction with an
      inverted repeated sequence, phO, located downstream of the phlA transcriptional
      start site. Cross-linking experiments indicate that PhlF can dimerize in
      solution, and thus PhlF may bind phO as a dimer or higher-order complex.
      Furthermore, it is now demonstrated that certain regulators of PHL synthesis act
      by modulating PhlF binding to phO. PHL, which has previously been shown to be an
      autoinducer of PHL biosynthesis, interacts with PhlF to destabilize the PhlF-phO
      complex. Conversely, the PhlF-phO complex is stabilized by the presence of
      salicylate, which has been shown to be an inhibitor of phlA expression.

PMID- 12003943
TI  - Characterization of the class 3 integron and the site-specific recombination
      system it determines.
AB  - Integrons capture gene cassettes by using a site-specific recombination
      mechanism. As only one class of integron and integron-determined site-specific
      recombination system has been studied in detail, the properties of a second
      class, the only known class 3 integron, were examined. The configuration of the
      three potentially definitive features of integrons, the intI3 gene, the adjacent
      attI3 recombination site, and the P(c) promoter that directs transcription of the
      cassettes, was similar to that found in the corresponding region (5' conserved
      segment) of class 1 integrons. The integron features are flanked by a copy of the
      terminal inverted repeat, IRi, from class 1 integrons on one side and a resolvase
      encoding tniR gene on the other, suggesting that they are part of a transposable
      element related to Tn402 but with the integron module in the opposite
      orientation. The IntI3 integrase was active and able to recognize and recombine
      both known types of IntI-specific recombination sites, the attI3 site in the
      integron, and different cassette-associated 59-be (59-base element) sites. Both
      integration of circularized cassettes into the attI3 site and excision of
      integrated cassettes were also catalyzed by IntI3. The attI3 site was localized
      to a short region adjacent to the intI3 gene. Recombination between a 59-be and
      secondary sites was also catalyzed by IntI3, but at frequencies significantly
      lower than observed with IntI1, the class 1 integron integrase.

PMID- 12003944
TI  - Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host
      system.
AB  - Pseudomonas aeruginosa is an important opportunistic pathogen that produces a
      variety of cell-associated and secreted virulence factors. P. aeruginosa
      infections are difficult to treat effectively because of the rapid emergence of
      antibiotic-resistant strains. In this study, we analyzed whether the amoeba
      Dictyostelium discoideum can be used as a simple model system to analyze the
      virulence of P. aeruginosa strains. The virulent wild-type strain PAO1 was shown
      to inhibit growth of D. discoideum. Isogenic mutants deficient in the las quorum
      sensing system were almost as inhibitory as the wild type, while rhl quorum
      sensing mutants permitted growth of Dictyostelium cells. Therefore, in this model
      system, factors controlled by the rhl quorum-sensing system were found to play a
      central role. Among these, rhamnolipids secreted by the wild-type strain PAO1
      could induce fast lysis of D. discoideum cells. By using this simple model
      system, we predicted that certain antibiotic-resistant mutants of P. aeruginosa
      should show reduced virulence. This result was confirmed in a rat model of acute
      pneumonia. Thus, D. discoideum could be used as a simple nonmammalian host system
      to assess pathogenicity of P. aeruginosa.

PMID- 12003945
TI  - Expression of Mycobacteriophage Ms6 lysis genes is driven by two sigma(70)-like
      promoters and is dependent on a transcription termination signal present in the
      leader RNA.
AB  - A mycobacteriophage Ms6 strong promoter region (P(lys)) was isolated by using
      transcriptional fusions with the lacZ reporter gene. Two tandem sigma(70)-like
      promoter sequences (P1 and P2) were found in this region. DNA sequencing of the
      promoter downstream region revealed a 214-bp leader sequence followed by five
      adjacent coding regions of 231 bp (ORF1), 1,152 bp (ORF2), 996 bp (ORF3), 231 bp
      (ORF4), and 372 (ORF5). ORF1 has the potential to encode a 77-amino-acid protein
      which revealed similarity to mycobacteriophage TM4 gp90, a predicted protein with
      unknown function. ORF2 encodes a 384-amino-acid protein which is related to
      several bacteriophage amidases. This protein induced cell lysis upon addition of
      chloroform, confirming its mureinolytic activity. ORF3 encodes a 332-amino-acid
      protein which is related to TM4 gp30, a protein with sequence similarity to
      amidases. ORF4 encodes a 77-amino-acid holin-like protein with significant
      similarity to the holin of Lactococcus lactis r1t bacteriophage. ORF5 encodes a
      124-amino-acid protein which is related to mycobacteriophage L5 gp30, a protein
      with unknown function. These data indicate that the promoter region P(lys) drives
      the transcription of the Ms6 lysis genes. An intrinsic transcription termination
      signal was identified in the leader sequence. Experiments using lacZ fusions
      showed that beta-galactosidase synthesis is inhibited when this transcription
      termination signal is present in the leader sequence. In conclusion,
      mycobacteriophage Ms6 cell lysis genes are expressed by their own promoter
      region, independently of virion structure and assembly protein genes. Moreover,
      an antitermination mechanism might be involved in their transcription regulation.

PMID- 12003946
TI  - Glycerol-3-phosphate-induced catabolite repression in Escherichia coli.
AB  - The formation of glycerol-3-phosphate (G3P) in cells growing on TB causes
      catabolite repression, as shown by the reduction in malT expression. For this
      repression to occur, the general proteins of the phosphoenolpyruvate-dependent
      phosphotransferase system (PTS), in particular EIIA(Glc), as well as the
      adenylate cyclase and the cyclic AMP-catabolite activator protein system, have to
      be present. We followed the level of EIIA(Glc) phosphorylation after the addition
      of glycerol or G3P. In contrast to glucose, which causes a dramatic shift to the
      dephosphorylated form, glycerol or G3P only slightly increased the amount of
      dephosphorylated EIIA(Glc). Isopropyl-beta-D-thiogalactopyranoside-induced
      overexpression of EIIA(Glc) did not prevent repression by G3P, excluding the
      possibility that G3P-mediated catabolite repression is due to the formation of
      unphosphorylated EIIA(Glc). A mutant carrying a C-terminally truncated adenylate
      cyclase was no longer subject to G3P-mediated repression. We conclude that the
      stimulation of adenylate cyclase by phosphorylated EIIA(Glc) is controlled by G3P
      and other phosphorylated sugars such as D-glucose-6-phosphate and is the basis
      for catabolite repression by non-PTS compounds. Further metabolism of these
      compounds is not necessary for repression. Two-dimensional polyacrylamide gel
      electrophoresis was used to obtain an overview of proteins that are subject to
      catabolite repression by glycerol. Some of the prominently repressed proteins
      were identified by peptide mass fingerprinting. Among these were periplasmic
      binding proteins (glutamine and oligopeptide binding protein, for example),
      enzymes of the tricarboxylic acid cycle, aldehyde dehydrogenase, Dps (a stress
      induced DNA binding protein), and D-tagatose-1,6-bisphosphate aldolase.

PMID- 12003947
TI  - Energetics of Helicobacter pylori and its implications for the mechanism of
      urease-dependent acid tolerance at pH 1.
AB  - In the presence of urea the neutrophilic human pathogen Helicobacter pylori
      survives for several hours at pH 1 with concomitant cytoplasmic pH homeostasis.
      To study this effect in detail, the transmembrane proton motive force and
      cytoplasmic urease activity of H. pylori were determined at various pH values. In
      the absence of urea, the organism maintained a close-to-neutral cytoplasm and an
      internally negative membrane potential at external pH values greater than 4 to 5.
      In the presence of urea, H. pylori accomplished cytoplasmic pH homeostasis down
      to an external pH of 1.2. At this external pH, the cytoplasmic pH was 4.9 and the
      membrane potential was slightly negative inside. The latter finding is in
      contrast to the situation in acidophiles, which develop inside-positive membrane
      potentials under similar conditions. Measurements of the time course of the
      membrane potential confirmed that addition of urea to the cells led to
      hyperpolarization. Most likely, this effect was due to electrogenic export of
      ammonium cations from the cytoplasm. The urease activity of intact cells
      increased nearly exponentially with decreasing external pH. This activation was
      not due to enhanced gene expression at low external pH values. In cell extracts
      the pH optimum of urease activity was dependent on the buffer system and was
      about pH 5 in sodium citrate buffer. Since this is the cytoplasmic pH of the
      cells at pH 1 to 2, we propose that cytoplasmic pH is a factor in the in vivo
      activation of the urease at low external pH values. The mechanism by which urease
      activity leads to cytoplasmic pH homeostasis in H. pylori is discussed.

PMID- 12003948
TI  - Characterization of a Mycoplasma pneumoniae hmw3 mutant: implications for
      attachment organelle assembly.
AB  - The proteins required for adherence of the pathogen Mycoplasma pneumoniae to host
      respiratory epithelial cells are localized to a polar structure, the attachment
      organelle. A number of these proteins have been characterized functionally by
      analysis of noncytadhering mutants, and many are components of the mycoplasma
      cytoskeleton. Mutations in some cytadherence-associated proteins have pleiotropic
      effects, including decreased stability of other proteins, loss of adherence and
      motility, and abnormal morphology. The function of protein HMW3, a component of
      the attachment organelle, has been difficult to discern due to lack of an
      appropriate mutant. In this paper, we report that loss of HMW3 resulted in
      decreased levels and more diffuse localization of cytoskeletal protein P65,
      subtle changes in morphology, inability to cluster the adhesin P1 consistently at
      the terminal organelle, reduced cytadherence, and, in some cells, an atypical
      electron-dense core in the attachment organelle. This phenotype suggests a role
      for HMW3 in the architecture and stability of the attachment organelle.

PMID- 12003949
TI  - The N terminus of the Escherichia coli transcription activator MalT is the domain
      of interaction with MalY.
AB  - The maltose system of Escherichia coli consists of a number of genes encoding
      proteins involved in the uptake and metabolism of maltose and maltodextrins. The
      system is positively regulated by MalT, its transcriptional activator. MalT
      activity is controlled by two regulatory circuits: a positive one with
      maltotriose as effector and a negative one involving several proteins. MalK, the
      ATP-hydrolyzing subunit of the cognate ABC transporter, MalY, an enzyme with the
      activity of a cystathionase, and Aes, an acetyl esterase, phenotypically act as
      repressors of MalT activity. By in vivo titration assays, we have shown that the
      N-terminal 250 amino acids of MalT contain the interaction site for MalY but not
      for MalK. This was confirmed by gel filtration analysis, where MalY was shown to
      coelute with the N-terminal MalT structural domain. Mutants in MalT causing
      elevated mal gene expression in the absence of exogenous maltodextrins were
      tested in their response to the three repressors. The different MalT mutations
      exhibited a various degree of sensitivity towards these repressors, but none was
      resistant to all of them. Some of them became nearly completely resistant to Aes
      while still being sensitive to MalY. These mutations are located at positions 38,
      220, 243, and 359, most likely defining the interaction patch with Aes on the
      three-dimensional structure of MalT.

PMID- 12003950
TI  - New type of osmoregulated solute transporter identified in halophilic members of
      the bacteria domain: TRAP transporter TeaABC mediates uptake of ectoine and
      hydroxyectoine in Halomonas elongata DSM 2581(T).
AB  - The halophilic bacterium Halomonas elongata synthesizes as its main compatible
      solute the aspartate derivative ectoine. We constructed a deletion mutant of H.
      elongata, KB1, defective in ectoine synthesis and tolerating elevated salt
      concentrations only in the presence of external compatible solutes. The
      dependency of KB1 on solute uptake for growth in high-salt medium was exploited
      to select insertion mutants unable to accumulate external solutes via
      osmoregulated transporters. One insertion mutant out of 7,200 failed to
      accumulate the osmoprotectants ectoine and hydroxyectoine. Genetic analysis of
      the insertion site proved that the mutation affected an open reading frame (ORF)
      of 1,281 bp (teaC). The nucleotide sequence upstream of teaC was determined, and
      two further ORFs of 603 bp (teaB) and 1,023 bp (teaA) were identified. Deletion
      of teaA and teaB proved that all three genes are mandatory for ectoine uptake.
      Sequence comparison showed significant identity of TeaA, TeaB, and TeaC to the
      transport proteins of the recently identified tripartite ATP-independent
      periplasmic transporter family (TRAP-T). The affinity of the cells for ectoines
      was determined (K(s) = 21.7 microM), suggesting that the transporter TeaABC
      exhibits high affinity for ectoines. An elevation of the external osmolarity
      resulted in a strong increase in ectoine uptake via TeaABC, demonstrating that
      this transporter is osmoregulated. Deletion of teaC and teaBC in the wild-type
      strain led to mutants which excreted significant amounts of ectoine into the
      medium when cultivated at high salt concentrations. Therefore, the physiological
      role of TeaABC may be primarily to recover ectoine leaking through the
      cytoplasmic membrane.

PMID- 12003951
TI  - Comparative sequence analysis of the symbiosis island of Mesorhizobium loti
      strain R7A.
AB  - The Mesorhizobium loti strain R7A symbiosis island is a 502-kb chromosomally
      integrated element which transfers to nonsymbiotic mesorhizobia in the
      environment, converting them to Lotus symbionts. It integrates into a
      phenylalanine tRNA gene in a process mediated by a P4-type integrase encoded at
      the left end of the element. We have determined the nucleotide sequence of the
      island and compared its deduced genetic complement with that reported for the 611
      kb putative symbiosis island of M. loti strain MAFF303099. The two islands share
      248 kb of DNA, with multiple deletions and insertions of up to 168 kb
      interrupting highly conserved colinear DNA regions in the two strains. The shared
      DNA regions contain all the genes likely to be required for Nod factor synthesis,
      nitrogen fixation, and island transfer. Transfer genes include a trb operon and a
      cluster of potential tra genes which are also present on the strain MAFF303099
      plasmid pMLb. The island lacks plasmid replication genes, suggesting that it is a
      site-specific conjugative transposon. The R7A island encodes a type IV secretion
      system with strong similarity to the vir pilus from Agrobacterium tumefaciens
      that is deleted from MAFF303099, which in turn encodes a type III secretion
      system not found on the R7A island. The 414 genes on the R7A island also include
      putative regulatory genes, transport genes, and an array of metabolic genes. Most
      of the unique hypothetical genes on the R7A island are strain-specific and
      clustered, suggesting that they may represent other acquired genetic elements
      rather than symbiotically relevant DNA.

PMID- 12003952
TI  - The ner gene of Photorhabdus: effects on primary-form-specific phenotypes and
      outer membrane protein composition.
AB  - The nematode-bacterium complex of Heterorhabditis-Photorhabdus is pathogenic to
      insect larvae. The bacteria undergo a form of phenotypic switching whereby the
      primary form, at the stationary phase of the growth cycle, makes a range of
      products and has the capacity to support nematode growth, whereas the secondary
      form does not express these phenotypes. The work described here investigated the
      mechanism regulating phenotypic variation by transforming the primary cells with
      secondary-form DNA on a low-copy-number vector and screening for colonies which
      did not produce the yellow pigment characteristic of primaries. Four
      transformants all carrying the same gene were found to loose primary-form
      specific characteristics, and the gene was sequenced and identified as ner, a
      regulatory gene in gram-negative bacteria and their phages. Unexpectedly,
      inactivation of the endogenous gene in the secondaries did not cause them to
      revert to the primary phenotype, and the gene was expressed in the primary form
      as well as the secondary form during exponential but not stationary phase and
      deregulated in the plasmid-bearing primary form. These and other pieces of
      evidence indicate that the endogenous ner gene is not responsible for the
      secondary phenotype, but that ner, when overexpressed, can repress expression of
      primary phenotypes at stationary phase. Inactivation of the endogenous ner gene
      in the primary form affected the outer membrane protein profile. A number of
      outer membrane proteins displayed differential accumulation in the primary and
      secondary forms at stationary phase, and two of the primary-form-specific
      proteins were absent from the ner primary strain.

PMID- 12003953
TI  - CcaR is an autoregulatory protein that binds to the ccaR and cefD-cmcI promoters
      of the cephamycin C-clavulanic acid cluster in Streptomyces clavuligerus.
AB  - The putative regulatory CcaR protein, which is encoded in the beta-lactam
      supercluster of Streptomyces clavuligerus, has been partially purified by
      ammonium sulfate precipitation and heparin affinity chromatography. In addition,
      it was expressed in Escherichia coli, purified as a His-tagged recombinant
      protein (rCcaR), and used to raise anti-rCcaR antibodies. The partially purified
      CcaR protein from S. clavuligerus was able to bind DNA fragments containing the
      promoter regions of the ccaR gene itself and the bidirectional cefD-cmcI promoter
      region. In contrast, CcaR did not bind to DNA fragments with the promoter regions
      of other genes of the cephamycin-clavulanic acid supercluster including lat, blp,
      claR, car-cyp, and the unlinked argR gene. The DNA shifts obtained with CcaR were
      prevented by anti-rCcaR immunoglobulin G (IgG) antibodies but not by anti-rabbit
      IgG antibodies. ccaR and the bidirectional cefD-cmcI promoter region were fused
      to the xylE reporter gene and expressed in Streptomyces lividans and S.
      clavuligerus. These constructs produced low catechol dioxygenase activity in the
      absence of CcaR; activity was increased 1.7- to 4.6-fold in cultures expressing
      CcaR. Amplification of the ccaR promoter region lacking its coding sequence in a
      high-copy-number plasmid in S. clavuligerus ATCC 27064 resulted in a reduced
      production of cephamycin C and clavulanic acid, by 12 to 20% and 40 to 60%,
      respectively, due to titration of the CcaR regulator. These findings confirm that
      CcaR is a positively acting autoregulatory protein able to bind to its own
      promoter as well as to the cefD-cmcI bidirectional promoter region.

PMID- 12003954
TI  - Functional role for a 2-oxo acid dehydrogenase in the halophilic archaeon
      Haloferax volcanii.
AB  - The archaeon Haloferax volcanii was previously shown to contain and transcribe
      the genes for a 2-oxo acid dehydrogenase (OADH) complex, but their presence
      remained a mystery because no enzymatic activity with any of the known OADH
      substrates could be found, and an inactivation of one of the genes did not lead
      to any phenotype. Here we report the identification of an additional oadh gene
      cluster in the genome of H. volcanii. In contrast to previously known oadh loci,
      it contains three genes, oadh2A1, oadh2A2, and oadh2ld, with coding capacity for
      the E1alpha and E1beta subunits and an unattached lipoyl domain, but it is devoid
      of the genes for a complete E2 and an E3. The genes were isolated by
      complementation of a nitrate respiration-deficient mutant of H. volcanii and
      therefore were shown to be functional in vivo. Phylogenetic analyses revealed
      that the deduced E1alpha and E1beta subunits of OADH2 group with bacterial
      acetoin dehydrogenases but not with the OADH1 subunits, and thus, H. volcanii has
      obtained the two gene groups independently. Comparison of the wild type and the
      mutant allowed us to exclude a function of OADH2 in the aerobic or anaerobic
      degradation of acetoin or glucose. Instead, it could be shown that OADH2 is
      important during nitrate-respirative growth on Casamino Acids. Many physiological
      and biochemical experiments failed to indicate that OADH2 uses any of the
      previously known OADH substrates. Growth potentials of the mutant were markedly
      different in media with a single carbon source versus media with mixed carbon
      sources.

PMID- 12003955
TI  - Examination of the Borrelia burgdorferi transcriptome in Ixodes scapularis during
      feeding.
AB  - Borrelia burgdorferi gene expression within the guts of engorging Ixodes
      scapularis ticks was examined by use of differential immunoscreening and
      differential expression with a customized amplified library. Fourteen chromosomal
      genes involved in energy metabolism, substrate transport, and signal transduction
      and 10 (4 chromosomal and 6 plasmid) genes encoding putative lipoproteins and
      periplasmic proteins were preferentially expressed in engorging ticks. These data
      demonstrate a new approach to the global analysis of B. burgdorferi genes that
      are preferentially expressed within the vector during feeding.

PMID- 12003956
TI  - Roles of internal cysteines in the function, localization, and reactivity of the
      TraV outer membrane lipoprotein encoded by the F plasmid.
AB  - We have examined the functional role of two internal cysteine residues of the F
      plasmid TraV outer membrane lipoprotein. Each was mutated to a serine separately
      and together to yield three mutant traV genes: traV(C10S), traV(C18S), and
      traV(C10S/C18S). All three cysteine mutations complemented a traV mutant for DNA
      donor activity and for sensitivity to donor-specific bacteriophage; however, when
      measured by a transduction assay, the donor-specific DNA bacteriophage
      sensitivities of the traV(C18S) and, especially, traV(C10S/C18S) mutant strains
      were significantly less than those of the traV(+) and traV(C10S) strains. Thus,
      unlike the Agrobacterium tumefaciens T-plasmid-encoded VirB7 outer membrane
      lipoprotein, TraV does not require either internal cysteine to retain significant
      biological activity. By Western blot analysis, all three mutant TraV proteins
      were shown to accumulate in the outer membrane. However, by nonreducing gel
      electrophoresis, wild-type TraV and especially the TraV(C18S) mutant were shown
      to form mixed disulfides with numerous cell envelope proteins. This was not
      observed with the TraV(C10S) or TraV(C10S/C18S) proteins. Thus, it appears that
      TraV C10 is unusually reactive and that this reactivity is reduced by C18,
      perhaps by intramolecular oxidation. Finally, whereas the TraV(C10S) and
      TraV(C18S) proteins fractionated primarily with the outer membrane, as did the
      wild-type protein, the TraV(C10S/C18S) protein was found in osmotic shock fluid
      and inner membrane fractions as well as outer membrane fractions. Hence, at least
      one cysteine is required for the efficient localization of TraV to the outer
      membrane.

PMID- 12003957
TI  - Construction and characterization of a cheA mutant of Treponema denticola.
AB  - The Treponema denticola cheA gene, encoding the central kinase of the general
      chemotaxis pathway, was analyzed for its role in chemotaxis and tissue
      penetration. The cheA gene was interrupted by insertion of an ermF-ermAM gene
      cassette. Reverse transcription-PCR confirmed that the other downstream
      chemotaxis genes within the same operon (cheW, cheX, and cheY) were still
      expressed in the cheA mutant strain. Lack of cheA resulted in decreased swarming
      on soft-agar swarm plates and failure to respond chemotactically to a mixture of
      nutrients. Behavioral analyses using video microscopy revealed that the cheA
      mutant exhibited coordinated cell movement. The cellular reversal frequency,
      however, was severely reduced, indicating that CheA in T. denticola mainly
      controls cellular reversal and that active chemotaxis signaling input is not
      required for coordination of flagellar rotation at both cell poles.

PMID- 12003958
TI  - Functional analysis of the Erwinia herbicola tutB gene and its product.
AB  - The tutB gene, which lies just downstream of tpl, has been cloned from Erwinia
      herbicola, and its product was analyzed. Despite its high sequence similarity to
      tryptophan transporters, TutB was found to be a tyrosine-specific transporter.
      Tryptophan acted as a competitive inhibitor of tyrosine transport. Unlike the
      tryptophanase operon, the tpl and tutB genes do not constitute an operon.

PMID- 12003959
TI  - Behavior of sister copies of mini-F plasmid after synchronized plasmid
      replication in Escherichia coli cells.
AB  - To clarify whether sister copies of mini-F plasmid are immediately separated from
      each other after replication, we analyzed the behavior of sister mini-F copies
      after synchronized replication of mini-F. Sister copies of mini-F were separated
      immediately or shortly after replication, in contrast to sister oriC copies of
      the Escherichia coli chromosome.

PMID- 12003960
TI  - Methylation of inorganic and organic selenium by the bacterial thiopurine
      methyltransferase.
AB  - Escherichia coli cells expressing the tpm gene encoding the bacterial thiopurine
      methyltransferase (bTPMT) are shown to methylate selenite and
      (methyl)selenocysteine into dimethylselenide (DMSe) and dimethyldiselenide
      (DMDSe). E. coli cells expressing tpm from a gene library cosmid clone (harboring
      a Pseudomonas syringae insert of about 20 kb) also methylated selenate into DMSe
      and DMDSe. bTPMT is the first methyltransferase shown to be involved in the
      methylation of these selenium derivatives.

PMID- 12003962
TI  - Role of newer fluoroquinolones in lower respiratory tract infections.

PMID- 12003963
TI  - Viral genome quantification as a tool for improving patient management: the
      example of HIV, HBV, HCV and CMV.
AB  - In recent years, new therapeutic options have led to enormous improvements in the
      management of certain chronic viral infections. Nevertheless, it has also become
      clear that such treatments require careful consideration and follow up. At the
      same time, a number of new technologies have been developed to measure
      quantitatively the concentration of viral genome in the patient's body fluids.
      Initially, these tests yielded important insights into the pathogenesis of viral
      infections and, in the case of human immunodeficiency virus (HIV), in fact
      revolutionized our understanding of its natural history. In addition, however,
      such 'viral load' tests have become vital tools in patient management; formerly
      pure research tools, they are now widely used in routine virological diagnosis,
      and a number of commercial assays have become available. In clinical virology,
      viral load testing serves four purposes: for diagnosis; to assess the patient's
      prognosis; as therapeutic markers to monitor the effect of antiviral treatment;
      and to estimate the patient's infectivity, i.e. the risk of transmission. In this
      review paper, we summarize the current role of viral genome quantification in the
      clinical management of patients infected with HIV, hepatitis B virus, hepatitis C
      virus and those at risk of developing human cytomegalovirus-related diseases.

PMID- 12003964
TI  - A prospective comparison of the two main indications of efavirenz in 2001 highly
      active antiretroviral therapy (HAART) regimens: first-line versus salvage use.
AB  - OBJECTIVE: To determine the efficacy of efavirenz introduction in first-line
      HAART compared with salvage multidrug regimens. PATIENTS AND METHODS: Prospective
      15 month comparison of 107 consecutive HIV-infected patients starting efavirenz,
      according to laboratory and clinical outcome of first-line versus rescue drug
      use, therapeutic history and association of selected antimicrobial agents: naive
      patients were compared with nucleoside reverse transcriptase inhibitor (NRTI)
      experienced patients in the first group, and patients in the second group who had
      one or more NRTI changed when starting a rescue treatment containing one or more
      novel protease inhibitors (PIs) were compared with those who did not. RESULTS:
      Efavirenz was administered with one or more novel NRTIs to 55 patients (27
      antiretroviral-naive and 28 patients experienced with NRTIs only), compared with
      52 patients who needed a multidrug salvage regimen after two or more failures of
      a 15-40 month PI-containing regimen. In an intention-to-treat analysis, con
      sidering early interruption or an unsatisfactory virological course as a failure,
      only one patient on salvage therapy completed a favourable 15 month follow-up,
      compared with 31 patients experiencing first-line efavirenz-based HAART (P <
      0.0001). The immunological response was less affected in both intensity and
      duration in patients undergoing rescue therapy. While no significant outcome
      difference was detected in the first group between naive and NRTI-experienced
      patients, among the salvage subjects the change of one or more NRTIs seemed to
      significantly improve virological and immunological outcome. Viral genotyping
      detected at least the K103N mutation in 41% of the 78 evaluable patients, despite
      lack of exposure to efavirenz and related compounds. Salvage patients had a
      significantly greater frequency of non-nucleoside RTI (NNRTI) resistance compared
      with the first-line group (P < 0.0001), in proportion to the extent of mutations
      affecting other drug classes (P < 0.0001). CONCLUSION: An efavirenz-based initial
      triple drug HAART proved significantly more effective than efavirenz adjunct to a
      rescue treatment performed after repeated failures of PI-based regimens. The
      unsatisfactory response of the salvage group was probably due to diffuse cross
      resistance descending from previous therapy, even when NNRTIs were never
      administered.

PMID- 12003965
TI  - A sub-inhibitory concentration of amphotericin B enhances candidastatic activity
      of interferon-gamma- and interleukin-13-treated murine peritoneal macrophages.
AB  - We studied the effects of interferon-gamma (IFN-gamma), a Th1 cytokine, and
      interleukin-13 (IL-13) or interleukin-4 (IL-4), Th2 cytokines, on the antifungal
      activity of resident murine peritoneal macrophages against Candida albicans 'in
      vitro'. IFN-gamma, IL-13 and IL-4 treatment enhanced the candidastatic functions
      of the macrophages. Reactive oxygen intermediates (ROIs) seem to be directly
      involved in the increase of anti-Candida activity in macrophages treated with Th1
      or Th2 cytokines. Study of unopsonized C. albicans phagocytosis showed that IFN
      gamma reduces the uptake process whereas the Th2 cytokines increase it. This
      difference is correlated to mannose receptor expression, which is decreased by
      IFN-gamma but increased by the Th2 cytokines. So, the effects on phagocytosis and
      candidastatic activity of IFN-gamma-treated macrophages are dissociated. In
      contrast, the phagocytic ability of macrophages pretreated 'in vitro' with IL-4
      or IL-13 played a complementary role to the ROIs, in reduction of yeast
      proliferation by macrophages. In consequence, the macrophages treated with IL-13
      and IL-4 develop a higher fungistatic activity than macrophages activated by IFN
      gamma. Amphotericin B associated with IL-13 or IFN-gamma, but not with IL-4,
      enhanced the yeast growth inhibition activity of macrophages. The ROIs were
      involved in the additive effect of IFN-gamma with amphotericin B, whereas another
      mechanism was implicated in the increase of candidastatic activity of macrophages
      treated with IL-13 in association with amphotericin B.

PMID- 12003966
TI  - In vitro susceptibilities of Zygomycota to polyenes.
AB  - The in vitro activity of polyenes was determined for 36 isolates of Zygomycota
      including Rhizopus spp. (15), Absidia corymbifera (10), Mucor spp. (6),
      Rhizomucor spp. (3), Cunninghamella bertholletiae (1) and Apophysomyces elegans
      (1). All isolates were tested with amphotericin B, heated amphotericin B and
      nystatin by a broth microdilution test. There were no significant differences
      between heated and unheated solutions of amphotericin B in terms of their
      antifungal activities. The MICs of amphotericin B for most of the strains were <2
      mg/L. For all isolates, nystatin was significantly less active than amphotericin
      B (P < 0.001). The one C. bertholletiae and one A. elegans isolates were less
      susceptible to amphotericin B (MICs 2 mg/L) and were also less susceptible to
      nystatin.

PMID- 12003967
TI  - Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by
      human monocytes through AP-1 and NF-kappa B transcription factors.
AB  - Erythromycin and other macrolides are effective for the treatment of chronic
      inflammatory airway diseases such as diffuse panbronchiolitis (DPB) and chronic
      sinusitis. The effect of macrolides in DPB is suggested to be anti-inflammatory
      rather than antibacterial. We investigated the effects of clarithromycin on
      interleukin-8 (IL-8) production using human peripheral monocytes and the human
      monocytic leukaemia cell line, THP-1. Bacterial extracts from Escherichia coli,
      Pseudomonas aeruginosa and Helicobacter pylori, as well as E. coli-derived
      lipopolysaccharide (LPS), induced IL-8 production. Clarithromycin suppressed this
      production in a dose-dependent manner in both monocytes and THP-1 cells (49.3
      75.0% inhibition at 10 mg/L). A luciferase reporter gene assay with plasmids
      containing a serially deleted IL-8 promoter fragment showed that both the
      activator protein-1 (AP-1) and/or the nuclear factor-kappa B (NF-kapp aB) binding
      sequences were responsible for the LPS and clarithromycin responsiveness of the
      IL-8 promoter. Consistently, in an electromobility shift assay, LPS increased the
      specific binding of both AP-1 and NF-kappaB, whereas clarithromycin suppressed
      it. Moreover, LPS and clarithromycin regulated three other promoters that have
      either the NF-kappa B or the AP-1 binding sequences: two synthetic (pAP-1-Luc and
      pNF-kappa B-Luc) and one naturally occurring (ELAM-Luc). Our results indicate
      that clarithromycin modified inflammation by sup-pressing IL-8 production and
      that clarithromycin may affect the expression of other genes through AP-1 and NF
      kappa B. In addition to treatment of airway diseases, the anti-inflammatory
      effect of macrolides may be beneficial for the treatment of other inflammatory
      diseases such as chronic gastritis caused by H. pylori.

PMID- 12003968
TI  - Serial passage of Chlamydia spp. in sub-inhibitory fluoroquinolone
      concentrations.
AB  - We investigated the in vitro development of fluoroquinolone resistance in
      Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae grown in McCoy
      cell monolayers in supplemented Eagle's minimum essential medium. With C.
      trachomatis, initial passages at sub-inhibitory fluoroquinolone concentrations
      did not affect fluoroquinolone susceptibility. However, after an initial lag of
      10-24 passages (depending upon the fluoroquinolone used), fluoroquinolone
      resistance developed rapidly. The final fluoroquinolone MIC after a total of 30
      passages was >256 times the MIC of the original wild-type strain with ofloxacin
      or ciprofloxacin passage. Analysis of the quinolone-resistance determining
      regions of two quinolone-resistant C. trachomatis mutants obtained after 30
      passages showed that both isolates had a single serine to isoleucine substitution
      at amino acid position 83 in GyrA. In stark contrast, with C. pneumoniae no
      reduced fluoroquinolone susceptibility could be sustained, even after 30 passages
      with moxifloxacin or ofloxacin. With sparfloxacin passage, some indication of
      resistance was observed but no viable organisms could be isolated for further
      investigation. It is possible that fluoroquinolone-resistant C. pneumoniae are
      less able to survive than wild type, which may explain why resistance does not
      develop readily.

PMID- 12003969
TI  - Effect of gemifloxacin on viability of Chlamydia pneumoniae (Chlamydophila
      pneumoniae) in an in vitro continuous infection model.
AB  - Persistent infection with Chlamydia pneumoniae (Chlamydophila pneumoniae) has
      been implicated in the development of atherosclerosis, asthma and other chronic
      diseases. However, data on treatment of C. pneumoniae infections are limited.
      Microbiological failure of antimicrobial therapy has been described, even after
      prolonged courses of treatment with azithromycin, doxycycline and erythromycin.
      Gemifloxacin is an enhanced-affinity fluoroquinolone with excellent activity
      against most common respiratory pathogens, including C. pneumoniae. The effect of
      prolonged treatment with gemifloxacin, compared with azithromycin, on viability
      of C. pneumoniae was investigated in a continuous infection model. Gemifloxacin
      at final con-centrations of 0.25 and 2.5 mg/L reduced the viability of C.
      pneumoniae by 5 log(10), which was similar to the effect of azithromycin.
      However, both antimicrobials failed to completely eliminate C. pneumoniae from
      continuously infected cells, even after 30 days of treatment. Both antibiotics
      decreased levels of interleukin-6 and interleukin-8 in this model, but this
      effect appeared to be secondary to the antichlamydial activity, as the cytokine
      levels correlated with the concentrations of microorganisms.

PMID- 12003970
TI  - Composition and antibiotic resistance profile of microcosm dental plaques before
      and after exposure to tetracycline.
AB  - The aim of this study was to investigate the effects of tetracycline
      administration on the viability and antibiotic resistance profiles of microcosm
      dental plaques. A constant depth film fermenter was used to generate multi
      species biofilms, which were grown for 216 h before tetracycline was added. The
      composition of the microcosm plaques was determined by viable counting on
      selective and non-selective media. The prevalence of antibiotic-resistant
      organisms was determined on antibiotic-containing media. Before administration of
      tetracycline, the biofilms had a total viable anaerobic count of 7 x 10(7) cfu
      per biofilm. They contained 7% lactobacilli, 19% streptococci and 2% Actinomyces
      spp. Immediately after pulsing with tetracycline, the composition of the biofilms
      changed and they consisted of 30% lactobacilli, 1.5% streptococci and 3%
      Actinomyces spp., with a total anaerobic count of 1 x 10(7) cfu per biofilm. The
      pre-valence and composition of the antibiotic-resistant microflora changed
      dramatically after the addition of tetracycline, with the proportion of the
      microflora displaying resistance to tetracycline increasing from 6% to 45%.
      Corresponding changes in the proportions of the microflora displaying resistance
      to other antibiotics were as follows: 5-28% for erythromycin, 1-5% for vancomycin
      and 0.4-3% for ampicillin. The results of this study have shown that the addition
      of tetracycline to microcosm dental plaques alters their composition and enriches
      for bacteria resistant to tetracycline and other unrelated agents.

PMID- 12003971
TI  - Prevalence and antibiotic resistance profile of mercury-resistant oral bacteria
      from children with and without mercury amalgam fillings.
AB  - Genes encoding resistance to mercury and to antibiotics are often carried on the
      same mobile genetic element and so it is possible that mercury-containing dental
      materials may select for bacteria resistant to mercury and to antibiotics. The
      main aim of this study was to determine whether the prevalence of Hg-resistant
      oral bacteria was greater in children with mercury amalgam fillings than in those
      without. A secondary aim was to determine whether the Hg-resistant isolates were
      also antibiotic resistant. Bacteria in dental plaque and saliva from 41 children
      with amalgam fillings and 42 children without such fillings were screened for
      mercury resistance by cultivation on a HgCl(2)-containing medium. Surviving
      organisms were identified and their susceptibility to mercury and to several
      antibiotics was determined. Seventy-eight per cent and 74% of children in the
      amalgam group and amalgam-free group, respectively, harboured Hg-resistant
      bacteria; this difference was not statistically significant. Nor was there any
      significant difference between the groups in terms of the proportions of Hg
      resistant bacteria in the oral microflora of the children. Of Hg-resistant
      bacteria, 88% and 92% from the amalgam group and the amalgam-free group,
      respectively, were streptococci; 41% and 33% were resistant to at least one
      antibiotic, most frequently tetracycline. The results of this study show that
      there was no significant difference between children with amalgam fillings and
      those without such fillings with regard to the prevalence, or the proportion, of
      Hg-resistant bacteria in their oral microflora. The study also found that Hg
      resistant bacteria were common in children regardless of whether or not they had
      amalgam fillings and that many of these organisms were also resistant to
      antibiotics.

PMID- 12003972
TI  - Rapid increase in macrolide resistance among penicillin non-susceptible
      pneumococci in Finland, 1996-2000.
AB  - The aims of this study were to evaluate the resistance patterns and
      serotypes/groups of penicillin non-susceptible pneumococci (PNSP) in Finland, and
      to determine phenotypes and resistance mechanisms of the erythromycin-resistant
      isolates. A total of 1190 PNSP were collected during 1996-2000 in Finland. The
      MICs of 18 antimicrobials were determined by the agar plate dilution method, and
      PCR was used to study the resistance mechanisms of the macrolide-resistant
      isolates. For serotyping, counterimmunoelectrophoresis and latex agglutination
      were used. Erythromycin resistance increased from 32% in 1996 to 62% in 2000
      among PNSP in Finland. Multiresistance (co-resistance to erythromycin,
      tetracycline and co-trimoxazole) was present in 22% of the isolates in 1996 and
      in 40% in 2000. The most common macrolide resistance phenotype was the MLS(B)
      phenotype (72%), 25% had the M phenotype and 3% the MS phenotype. The MLS(B) and
      M phenotypes increased in the same proportion during the study period. All the
      MLS(B) isolates had the erm(B) gene, the M isolates the mef(A) gene, and in 11 MS
      isolates, ribosomal mutations were the cause of resistance. The most common
      serotypes/groups were 14, 19 and 6. We found a significant increase in
      multiresistance among PNSP within a short period of time in Finland. Although
      pneumococcal resistance to erythromycin was 11% in 2000, the same figure was 50%
      among the PNSP. The rise in erythromycin resistance is worrying, as macrolides
      are commonly used as first- and second-line drugs in pneumococcal infections.

PMID- 12003973
TI  - Detection and expression of methicillin/oxacillin resistance in multidrug
      resistant and non-multidrug-resistant Staphylococcus aureus in Central Sydney,
      Australia.
AB  - Ninety clinical Staphylococcus aureus isolates from separate patients were
      examined phenotypically and genotypically for susceptibility to
      methicillin/oxacillin. Thirty were methicillin/oxacillin susceptible and 60 were
      methicillin and oxacillin resistant (MRSA). The 60 MRSA isolates examined were
      subdivided into two groups according to their antibiotic profiles and comprised
      30 non-multidrug-resistant (NMDR) isolates, resistant to less than two non-beta
      lactam antibiotics, and 30 multidrug-resistant (MDR) isolates, resistant to three
      or more non-beta-lactam antibiotics. Phenotypic and genotypic analysis of
      methicillin/oxacillin showed that despite use of the guidelines published by the
      NCCLS for the testing of S. aureus susceptibility to methicillin/oxacillin, MIC
      values of some NMDR MRSA isolates fell below the NCCLS-recommended breakpoints.
      Etest strips failed to detect two NMDR MRSA isolates tested with oxacillin and
      four tested with methicillin. Lowering the NCCLS-recommended oxacillin screen
      agar concentration from 6 to 2 mg/L and temperature of incubation to 30 degrees
      C, improved the specificity and sensitivity of NMDR MRSA detection from 87% to
      100%. On PFGE analysis these NMDR MRSA strains were genotypically different.
      Genotypic tests, such as multiplex PCR for the mecA/nuc genes and DNA
      hybridization for the mecA gene, or phenotypic monoclonal antibody-based tests to
      detect penicillin-binding protein 2a (PBP2a) offer advantages for problematic
      isolates in detecting or confirming low-level phenotypic heterogeneous mecA
      expression of oxacillin and methicillin resistance in NMDR MRSA.

PMID- 12003974
TI  - Antimicrobial susceptibility patterns of Campylobacter jejuni strains isolated
      from hospitalized children in Athens, Greece.
AB  - The antimicrobial susceptibility of 129 Campylobacter jejuni strains, isolated
      from hospitalized children with gastroenteritis, to five antimicrobials,
      including nalidixic acid, ciprofloxacin, erythromycin, ampicillin and co
      amoxiclav, was determined. Isolates belonged to two time periods: group A
      contained strains isolated in 1987-1988; and group B 1998-2000. Antimicrobial
      susceptibility patterns differed significantly between the two groups with
      respect to quinolones, with an increase in the percentage of resistant strains in
      group B (30.6% versus 0% in group A), whereas erythromycin, ampicillin and co
      amoxiclav were effective drugs in both groups.

PMID- 12003975
TI  - Pharmacodynamic activity of fluoroquinolones against ciprofloxacin-resistant
      Streptococcus pneumoniae.
AB  - The susceptibility and pharmacodynamic activity of ciprofloxacin and new
      fluoroquinolones were studied against low-level (MIC 4 mg/L) and high-level (MIC
      16 mg/L) ciprofloxacin-resistant Streptococcus pneumoniae. An in vitro
      pharmacodynamic model simulating free fluoroquinolone (protein unbound) serum
      concentrations, using Cp(max) and AUC(0-24) achieved (in healthy volunteers)
      after standard oral doses that are used for community-acquired respiratory
      infections, was used to compare bacterial killing by five fluoroquinolones
      against six ciprofloxacin-resistant S. pneumoniae isolates (four different
      resistance mutant phenotypes: ParC, efflux, ParC with efflux, and ParC and GyrA)
      obtained from an ongoing Canadian respiratory organism surveillance study. The
      potency (MIC only) of fluoroquinolones was gemifloxacin > moxifloxacin >
      gatifloxacin > levofloxacin > ciprofloxacin. Ciprofloxacin (free AUC(0-24)/MIC
      0.9-3.5) produced no reduction of growth at 6, 24 or 48 h compared with the
      initial inoculum in all six strains. Levofloxacin (free AUC(0-24)/MIC 18-35) was
      bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h for the ParC as well as
      the efflux mutants, but only bactericidal at 24 h for the ParC with efflux
      strain. Levofloxacin (free AUC(0-24)/MIC 4.4) demonstrated no reduction of growth
      relative to the initial inoculum against the ParC and GyrA mutants. Gatifloxacin
      and moxifloxacin (free AUC(0-24)/MIC 48 and 60, respectively) were bactericidal
      at 6, 24 and 48 h against the ParC, efflux, and ParC with efflux mutants, but
      demonstrated little to no growth reduction (free AUC(0-24)/MIC 6 and 7.5,
      respectively) in ParC and GyrA mutants. Gemifloxacin (free AUC(0-24)/MIC 67-133)
      was bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h in all low-level
      ciprofloxacin-resistant S. pneumoniae mutants. Against two of the ParC and GyrA
      mutants, gemifloxacin (free AUC(0-24)/MIC 32) was bactericidal at 6, 24 and 48 h
      but against one ParC and GyrA mutant (free AUC(0-24)/MIC 16) gemifloxacin
      demonstrated reduced activity with initial killing at 24 h but with subsequent
      regrowth. These data indicate that ciprofloxacin produces no inhibition of growth
      of low- or high-level ciprofloxacin-resistant S. pneumoniae, whereas
      gatifloxacin, levofloxacin and moxifloxacin
      (moxifloxacin>gatifloxacin>levofloxacin) were bactericidal for low-level
      resistant strains but produced little or no inhibition of high-level resistant
      strains. Gemifloxacin at simulated free AUC(0-24)/MIC > or = 32, was bactericidal
      against low- and high-level resistant strains. When simulated free AUC(0-24)/ MIC
      was <16, gemifloxacin allowed regrowth of high-level ciprofloxacin-resistant
      strains.

PMID- 12003976
TI  - Enhanced antifungal efficacy in experimental invasive pulmonary aspergillosis by
      combination of AmBisome with Fungizone as assessed by several parameters of
      antifungal response.
AB  - In common with a proportion of patients with invasive pulmonary aspergillosis
      (IPA), the efficacy of AmBisome treatment regimens in our rat model remains
      suboptimal. To investigate whether this might be the result of initially low
      antifungal activity of amphotericin B at the site of infection when administered
      in the liposomal form, Fungizone was added to AmBisome at the start of treatment.
      Groups of granulocytopenic rats with left-sided IPA received 10 day treatment
      regimens with either AmBisome 10 mg/kg/day (n = 25) or AmBisome 10 mg/kg/day
      combined with a single dose of Fungizone 1 mg/kg at day 1 (n = 27). Parameters of
      treatment response included survival, serum galactomannan (GM), size and quality
      of pulmonary macroscopic lesions, lung weight, viable fungal counts (cfu) and
      chitin content of the infected lung, and extra-pulmonary disseminated fungal
      infection. In a separate experiment the significance of early start of treatment
      to obtain therapeutic efficacy was investigated. Compared with untreated
      controls, both treatment regimens showed a significant increase in survival and
      change in parameters of fungal infection except left lung cfu. The combination
      treatment showed a significant increase in survival compared with AmBisome
      monotherapy (P = 0.02) and a significant decrease in left lung chitin content (P
      = 0.03). Differences in circulating GM concentrations between the two treatment
      regimes approached significance (P = 0.06). Delay in the start of treatment from
      16 to 24 h after fungal inoculation resulted in a significant decrease in
      therapeutic efficacy (P = 0.02). It is concluded that the efficacy of AmBisome
      therapy can be enhanced by the addition of Fungizone at the start of treatment.
      This is probably a result of active amphotericin B being immediately available in
      the lung at the start of treatment.

PMID- 12003977
TI  - A prospective, multicentre study of moxifloxacin concentrations in the sinus
      mucosa tissue of patients undergoing elective surgery of the sinus.
AB  - A pharmacokinetic study was carried out to determine moxifloxacin concentrations
      in sinus tissue, after oral moxifloxacin 400 mg once daily for 5 days to patients
      with chronic sinusitis, undergoing elective sinus surgery. Patients were randomly
      allocated to one of seven treatment groups, in which tissues were sampled 2, 3,
      4, 6, 12, 24 or 36 h post-dose. A control group with non-infected nasal polyps
      was also included. Forty-eight patients (13 female, 35 male, mean age 47.1 years)
      were allocated to one of each active treatment group (n = 42) or to the control
      group (n = 6). Tissue and plasma samples were taken simultaneously and stored
      frozen until assayed by HPLC. Thirty-nine patients were fully valid for
      pharmacokinetic analysis. The geometric mean moxifloxacin plasma concentration
      increased from 2.32 mg/L at 2 h to a maximum of 3.37 mg/L at 4 h post-dose,
      decreasing to 0.37 mg/L at 36 h post-dose. The moxifloxacin concentration in
      sinus mucosa was consistently greater than that in plasma being 4.56-5.73 mg/kg
      from 2 to 6 h and 2.81-1.25 mg/kg from 12 to 36 h post-dose. The elimination
      rates in plasma and sinus tissues were similar. The tissue/plasma ratio was c.
      200% between 2 and 6 h, and up to 328.9% at 36 h. Results were similar whatever
      the site of tissue sampling (maxillary sinus, anterior ethmoid sinus or nasal
      polyps). Tissue levels exceeded the MIC(90) of all pathogens commonly causing
      acute sinusitis (e.g. 5-30 x MIC for Streptococcus pneumoniae: 0.25 mg/L). These
      results sup-port the use of moxifloxacin 400 mg once daily as a regimen for the
      treatment of sinus infections.

PMID- 12003978
TI  - The successful introduction of a programme to reduce the use of i.v.
      ciprofloxacin in hospital.
AB  - The effectiveness of a programme to reduce the use of i.v. ciprofloxacin was
      assessed. i.v. ciprofloxacin was removed from ward stock and discussion occurred
      regarding appropriate use of the drug. Six months later, a factsheet containing
      recommendations was distributed to all medical staff and a requirement for
      justification before prescription was introduced. The programme reduced
      expenditure on i.v. ciprofloxacin to 34% of original levels. Savings of > 36,000
      pounds sterling were made for two consecutive years. A sustained reduction in the
      use of i.v. ciprofloxacin was obtained by a combination of education and
      restriction.

PMID- 12003979
TI  - Comparison of selection for mutants with reduced susceptibility to ABT-773,
      erythromycin and rifampicin in respiratory tract pathogens.
AB  - Attempts were made to select mutants on agar media containing the new ketolide
      ABT-773, erythromycin or rifampicin, at concentrations above the MICs, from
      Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and
      Haemophilus influenzae, including erythromycin-resistant strains. ABT-773 did not
      select for mutants in four strains, whereas in eight strains the frequencies at
      72 h were < or = 10(-9). ABT-773 MICs were 0.015-4 mg/L for mutants, except those
      selected from inducible Erm(A) S. aureus. Mutants selected on ABT-773 or
      erythromycin were cross-resistant to ABT-773, erythromycin and, sometimes,
      clindamycin. The susceptibility profiles indicate that different mutations were
      selected and that ABT-773 and erythromycin may interact with the ribosome
      differently.

PMID- 12003980
TI  - Molecular characterization of metallo-beta-lactamase-producing Acinetobacter
      baumannii and Acinetobacter genomospecies 3 from Korea: identification of two new
      integrons carrying the bla(VIM-2) gene cassettes.
AB  - Carbapenem-resistant Acinetobacter spp. used to be rare, but are increasingly
      isolated in Korea. Among 28 isolates of imipenem-resistant Acinetobacter spp.
      found in a Korean hospital in 1998 and 1999, 14 produced metallo-beta-lactamases.
      The bla(VIM-2) gene was detected, by PCR, in 11 and two isolates of Acinetobacter
      baumannii and Acinetobacter genomospecies 3, respectively, and bla(IMP-1) in one
      isolate of A. baumannii. The MICs of imipenem for the isolates were 8-32 mg/L.
      PFGE analysis of SmaI-digested genomic DNA gave identical patterns in eight of 11
      bla(VIM-2)-positive A. baumannii isolates from respiratory specimens of ICU
      patients. The bla(VIM-2) gene cassettes in the isolates are identical to those
      from Pseudomonas aeruginosa isolates in Europe, but are inserted into new class I
      integrons In105 and In106. The attC site of the last cassette of the array in
      In106 is interrupted by the insertion of a putative class II intron. This is the
      first report of VIM-2 beta-lactamase-producing A. baumannii and Acinetobacter
      genomospecies 3. Production of the VIM-2 enzyme presents an emerging threat of
      carbapenem resistance among Acinetobacter spp. in Korea.

PMID- 12003981
TI  - Molecular analysis of vancomycin-resistant Enterococcus faecalis from Michigan
      hospitals during a 10 year period.
AB  - We evaluated the molecular relatedness of 47 clinical isolates of vancomycin
      resistant Enterococcus faecalis collected from 15 Michigan hospitals from 1991 to
      2000. There were 17 PFGE strain types for the 47 isolates. Ten of 15 hospitals
      demonstrated interhospital, and three of 15 intrahospital, dissemination of some
      isolates. Forty-two isolates (89.4%) demonstrated vanB resistance. All vanA
      isolates comprised unique PFGE groups, suggesting transposon dissemination or the
      presence of a similar plasmid. The results of this study suggest inter- and
      intrahospital dissemination of strains of vancomycin-resistant E. faecalis during
      a 10 year period in Michigan.

PMID- 12003982
TI  - In vitro activity of a new cephalosporin, RWJ-54428, against streptococci,
      enterococci and staphylococci, including glycopeptide-intermediate Staphylococcus
      aureus.
AB  - The need for new antimicrobial agents with activity against Gram-positive
      organisms has become increasingly important because of emerging resistance. We
      compared the activity of a new b-lactam antimicrobial agent, RWJ-54428 (MC-02
      479), with representatives of other classes of antimicrobial agents against 76
      Staphylococcus aureus (including four glycopeptide- intermediate strains), 50
      coagulase-negative staphylococci, 20 Enterococcus faecalis, 20 Enterococcus
      faecium, 10 Enterococcus gallinarum/Enterococcus casseliflavus, 54 Streptococcus
      pneumoniae and 22 viridans streptococcal isolates. The MIC(90) of RWJ-54,428 was
      < or = 2 mg/L for all groups of bacteria tested except E. faecium. The activity
      against four strains of glycopeptide-intermediate S. aureus was similar to that
      for other methicillin-resistant S. aureus isolates (range 0.5-2.0 mg/L).

PMID- 12003983
TI  - BMS284756 (formerly T-3811, a des-fluoroquinolone) potency and spectrum tested
      against over 10,000 bacterial bloodstream infection isolates from the SENTRY
      antimicrobial surveillance programme (2000).
AB  - BMS284756 is a novel des-F (6)-quinolone, which has a wide range of activity
      against many species of Gram-positive and -negative organisms. The potency of
      BMS284756 was compared with that of other quinolones, including ciprofloxacin,
      gatifloxacin and levofloxacin, and was tested against >10,000 bloodstream
      isolates from the year 2000 SENTRY antimicrobial surveillance programme. Twelve
      pathogens accounted for nearly all of the referred isolates and included
      Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli,
      Klebsiella pneumoniae, Enterobacter spp., Serratia spp., Pseudomonas aeruginosa,
      Acinetobacter spp., Enterococcus spp., Streptococcus pneumoniae and beta
      haemolytic or viridans group streptococci. Of the four quinolones tested,
      BMS284756 was the most active overall against Staphylococcus spp. (MIC(50) < or =
      0.03 mg/L) and Streptococcus spp. (MIC(50) 0.06 mg/L). In contrast, BMS284756 was
      less potent than the other quinolones against the enteric Gram-negative bacilli
      (MIC(50) < or = 0.03-1 mg/L). With a proposed breakpoint of < or =4 mg/L,
      BMS284756 may be a therapeutic alternative pending the results of clinical
      trials.

PMID- 12003984
TI  - Intracellular activity of ABT-773 and other antimicrobial agents against
      Legionella pneumophila.
AB  - The intracellular activity of ABT-773 against Legionella pneumophila was compared
      with azithromycin and ciprofloxacin using HL-60 cells. Against L. pneumophila
      ATCC 33152 and three clinical isolates the MICs (mg/L) were ABT-773 0.015,
      ciprofloxacin 0.03 and azithromycin 0.03. At 48 h, the mean percentage inhibition
      was as follows: 28.5 +/- 5.9% and 32.6 +/- 4.6% at 8 x and 16 x MIC of ABT-773;
      38.1 +/- 8.6% and 48.2 +/- 7.0% at 8 x and 16 x MIC of ciprofloxacin; and 26.3 +/
      9.9% and 28.5 +/- 9.9% at 8 x and 16 x MIC of azithromycin. In this study, all
      three agents were highly active, with ABT-773 demonstrating similar activity to
      azithromycin against L. pneumophila.

PMID- 12003985
TI  - Antibiotic tolerance of peritoneal bacterial isolates in dialysis fluids.
AB  - The objective was to test antibiotic activity against Staphylococcus epidermidis
      and Pseudomonas aeruginosa in fresh dianeal fluid and spent dialysate from
      patients undergoing chronic ambulatory peritoneal dialysis. MICs and MBCs were
      measured and compared with those in standard broth. For S. epidermidis, there was
      some reduction in cefazolin and vancomycin activity in dialysis fluids. For P.
      aeruginosa, ciprofloxacin and tobramycin MICs increased significantly, and all
      isolates were tolerant to ceftazidime and piperacillin in dialysis fluids.
      Dialysis fluids can significantly impair antibiotic activity. The clinical
      implications warrant further study of antibiotic pharmacodynamics in the
      treatment of peritonitis.

PMID- 12003986
TI  - Effect of clarithromycin on chronic respiratory infection caused by Pseudomonas
      aeruginosa with biofilm formation in an experimental murine model.
AB  - Fourteen-membered macrolides (e.g. clarithromycin and erythromycin), but not 16
      membered macrolides (e.g. josamycin), are effective in diffuse panbronchiolitis.
      However, there are no studies that have compared the effects of 14- and 16
      membered macrolide antibiotics on biofilm formation. Treatment with high-dose
      clarithromycin (100 mg/kg) resulted in a significant decrease in the number of
      viable bacteria in an experimental murine model. Josamycin at a dose of up to 100
      mg/kg had no effect on the number of viable bacteria in the lung. Our results may
      explain, at least in part, the clinical efficacy of 14-membered macrolide
      antibiotics in patients with chronic pneumonia caused by Pseudomonas aeruginosa.

PMID- 12003987
TI  - Evaluation of two inhibitors of invasion: LY311727 [3-(3-acetamide-1-benzyl-2
      ethyl-indolyl-5-oxy)propane phosphonic acid] and AEBSF [4-(2-aminoethyl)
      benzenesulphonyl fluoride] in acute murine toxoplasmosis.
AB  - We examined the effect of an inhibitor of secretory phospholipase A2 type II
      (LY311727) and of a specific inhibitor of serine proteases (AEBSF) in a murine
      model of acute toxoplasmosis. LY311727 did not afford any significant protection
      and produced earlier mortality compared with untreated mice at a dose of 100
      mg/kg. In contrast, AEBSF demonstrated a significant increase in length of
      survival, and this effect was enhanced when AEBSF was administered with non
      protective doses of pyrimethamine.

PMID- 12003988
TI  - A randomized controlled trial of azithromycin versus doxycycline/ciprofloxacin
      for the syndromic management of sexually transmitted infections in a resource
      poor setting.
AB  - A randomized controlled trial was carried out to assess the effectiveness of
      azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the
      treatment of sexually transmitted infections in a resource-poor environment.
      Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the
      azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting
      in three treatment failures. Gonorrhoea was cured in 55/56 (98.2%) women, with
      one treatment failure in a patient with concomitant C. trachomatis infection.
      These results indicate that a single oral dose of azithromycin may prove to be a
      more effective and convenient treatment for sexually transmitted infections in
      women in a resource-poor environment

PMID- 12003989
TI  - In vitro bactericidal activity and post-antibiotic effect of ABT-773 versus co
      amoxiclav against anaerobes.

PMID- 12003990
TI  - Urinary tract-derived Escherichia coli resistant to co-trimoxazole in Japan,
      where the drug is seldom used for treating acute urinary tract infections.

PMID- 12003992
TI  - Leukocyte-endothelial cell interactions in the inflammatory response.

PMID- 12003993
TI  - Molecular phenotype distinguishes two subsets of gastric low-grade mucosa
      associated lymphoid tissue lymphomas.
AB  - Isotype switch recombination together with somatic mutation of immunoglobulin
      variable genes is indicative of B-cell maturation stage. Because aberrant isotype
      switch events occur in a proportion of gastric mucosa-associated lymphoid tissue
      (MALT) lymphomas, we tested whether gastric MALT lymphomas with or without
      aberrant rearrangements in the switch regions differ in B-cell maturation stage.
      Southern blot analysis of DNA from six gastric MALT lymphoma cases revealed the
      presence of aberrant isotype switch events in three cases. Somatic common
      mutations were present in all immunoglobulin variable heavy chain genes of the
      six cases, and homology with the closest germline ranged from 89.5% to 98.8%.
      Replacement versus silent mutation ratio analysis of complementarity-determining
      regions and frameworks indicated the positive selective pressure of an antigen in
      four cases. In the remaining two cases, protein translated from the third
      complementarity-determining region suggested the selective pressure of an
      autoantigen. The three cases with aberrant isotype switch events showed no
      uncommon mutations, whereas two of three cases without evidence of aberrant
      isotype switch showed high levels of such mutations. Moreover the three cases
      with aberrant isotype switch, compared with the three cases without, showed an
      increased number of common mutations and of N segment additions. These data raise
      the possibility of two distinct subsets of gastric low-grade MALT lymphomas, one
      with aberrant isotype switch and no intraclonal diversification, and one with no
      aberrant isotype switch but with intraclonal diversification. The first subset
      may originate from a post-germinal center environment and the second from a
      germinal center. Alternatively, the first subset may derive from the second after
      maturation or after a transformation event that blocks the mutational process.

PMID- 12003994
TI  - Polymorphism of the uteroglobin gene in systemic lupus erythematosus and IgA
      nephropathy.
AB  - Uteroglobin (UG) is a multifunctional protein with anti
      inflammatory/immunomodulatory properties. The UG gene is located on the long arm
      of chromosome 11 (11q12.3-q13.1) in a region linked to some immune disorders. A
      guanine-adenine substitution at position 38 (A38G) has been found in the
      noncoding region of exon 1 that is significantly correlated with an increased
      risk of developing immune-mediated diseases. Recently an experimental model of UG
      knockout mice showed that in mice, UG deficiency causes severe glomerulopathy
      with mesangial deposition of IgA-fibronectin complexes. To detect the presence of
      polymorphisms in the UG coding sequence, the DNA of 109 patients with IgA
      nephropathy (IgAN), and 32 patients with systemic lupus erythematosus (SLE) were
      tested for the nucleotide sequence of all three UG exons by heteroduplex
      analysis. We detected heterozygous DNA only for exon 1 due to the A38G
      substitution, as confirmed by sequencing. We tested for A38G polymorphism, by
      restriction endonuclease digestion (Sau96I), both in SLE patients and in IgAN
      patients. Twenty patients with either membranous nephropathy (12) or focal and
      segmental glomerular sclerosis and 120 healthy subjects served as controls.
      Compared with both healthy controls and non-IgA control patients, the frequency
      of the 38A allele was significantly higher in SLE patients (38 of 64 alleles
      versus 89 of 240 alleles, p = 0.002, and versus 7 of 40 alleles, p < 0.001). IgAN
      patients showed an allelic distribution similar to both control groups. A
      subgroup of 18 IgAN patients undergoing renal replacement therapy because of end
      stage renal disease showed a significant increase in 38A allele frequency (5 of
      36 38G alleles versus 31 of 36 38A alleles, p < 0.001). UG is an immunomodulatory
      agent that is able to (a) inhibit the activity of several phospholipase A2
      (PLA2s), (b) interfere with the function of both neutrophils and monocytes, and
      (c) prevent immune recognition, perhaps by masking surface antigens. This could
      account for the role this molecule plays in SLE. The A38G polymorphism is located
      within a region corresponding to the rat minimal promoter that proved to be
      important in the transcriptional regulation of UG. Although the significance of
      any alterations in the UG exon 1 noncoding region in humans has yet to be
      clarified, initial evidence suggests that it may alter the control of immune
      response and of inflammation.

PMID- 12003995
TI  - Chromosomal alterations in hepatocellular nodules by comparative genomic
      hybridization: high-grade dysplastic nodules represent early stages of
      hepatocellular carcinoma.
AB  - Data from experimental hepatocarcinogenesis and recent studies in humans have
      suggested that the emergence of hepatocellular carcinoma (HCC) is a stepwise
      process. However, despite abundant experimental data, the precise molecular
      mechanisms and genetic alterations involved in human liver carcinogenesis are
      still unclear. Comparative genomic hybridization was used to analyze 26
      hepatocellular nodules obtained from patients undergoing liver transplantation or
      surgical resection for HCC. According to the criteria proposed by the
      International Working Party, 16 nodules were classified as multiacinar
      regenerative nodules (MRN), 4 as low-grade dysplastic nodules (LG-DN), and 6 as
      high-grade dysplastic nodules (HG-DN). Our aim was to investigate the possible
      genetic differences between MRN, LG-DN, and HG-DN. The whole group of nodules
      showed only a few aberrations (mean 1.1/case), without any significant pattern.
      This finding is comparable to what happens in non-neoplastic tissue. On the
      contrary, in three of six HG-DN, we found deletions of 8p and gains of 1q. LG-DN
      and MRN did not show these chromosomal imbalances. These results confirm the
      important role of allelic losses on 8p as well as of gains of 1q in HCC. We
      conclude that the genes that are important in early stages of
      hepatocarcinogenesis are probably located on these chromosomal arms.

PMID- 12003996
TI  - Microvessel morphology and vascular endothelial growth factor expression in human
      colonic carcinoma with or without metastasis.
AB  - We quantified microvessel morphology and vascular endothelial growth factor
      (VEGF) expression in human colonic carcinoma with or without metastasis. The
      cancerous growth and the noncancerous section of surgical specimens from 36
      patients with colorectal carcinoma (14 without metastasis and 22 with metastasis)
      were studied. Tissue slices immunostained with CD34 were processed for
      microvessel counts (per mm(2)), the mean diameter of microvessels (microm), and
      the mean spatial direction of microvessels (degree), defined by the angle between
      the longitudinal axis of microvessels and the direction perpendicular to the
      surface of the mucosa. Tissue slices immunostained with anti-VEGF antibody were
      processed for total epithelial cell counts (per mm(2)), VEGF-positive cell counts
      (per mm(2)), and VEGF-positive ratio (%). Carcinoma without metastasis had
      significantly larger microvessel counts (213 +/- 77, p < 0.01), larger
      microvessel diameter (7.99 +/- 1.77, p < 0.05), and larger spatial direction
      (47.2 +/- 8.3, p < 0.01) than normal tissue (144 +/- 49 for microvessel counts;
      7.03 +/- 0.90 for microvessel diameter; 39.5 +/- 6.6 for spatial direction).
      Compared with carcinoma without metastasis, carcinoma with metastasis had a
      significantly larger microvessel diameter (9.75 +/- 2.65, p < 0.03) and lower
      microvessel counts (180 +/- 92, p = 0.51). Carcinoma without metastasis had a
      significantly larger VEGF-positive cell count (1276 +/- 805, p < 0.05) and larger
      VEGF-positive ratio (53.6 +/- 39.3, p < 0.05) than normal tissue (571 +/- 553 for
      VEGF-positive cell counts; 24.6 +/- 23.2 for VEGF-positive ratio). Carcinoma with
      metastasis had a significantly lower total cell count (1443 +/- 237, p < 0.001)
      and lower VEGF-positive cell count (716 +/- 463, p < 0.05) than carcinoma without
      metastasis. With tumor progression, microvessel diameter significantly increased
      and microvessel counts decreased, which can be in part explained by VEGF
      expression. The microvessel diameter seems to be the dominant parameter
      responsible for cancer cell intravasation as the first step of metastasis.

PMID- 12003997
TI  - Decay-accelerating factor confers protection against complement-mediated podocyte
      injury in acute nephrotoxic nephritis.
AB  - SUMMARY: Decay-accelerating factor (DAF or CD55) is one of a set of regulators
      that function to protect self cells from deposition of autologous C3b on their
      surfaces. Its relative importance in vivo, however, is incompletely understood.
      As one approach to address this issue, we induced nephrotoxic serum (NTS)
      nephritis in wild-type mice and Daf1 gene-floxed mice devoid of renal DAF
      expression. For these experiments NTS IgG was administered at a dose (0.5 mg iv)
      that requires complement for glomerular injury. After 18 hours, renal injury was
      assessed by proteinuria and by histologic, immunohistochemical, and electron
      microscopic analyses of kidneys. Fifteen normal and 15 DAF-deficient mice were
      studied. Baseline albuminuria in the Daf1(-/-) mice was 115.9 +/- 41.4 microg/mg
      creatinine as compared with 85.7 +/- 32.3 microg/mg creatinine in their Daf1(+/+)
      littermates (p = 0.075). After administration of NTS IgG, albuminuria increased
      to 2001.7 +/- 688.7 microg/mg creatinine as compared with 799.7 +/- 340.5
      microg/mg creatinine in the controls (p = 0.0003). Glomerular histology was
      similar in Daf1(-/-) and Daf1(+/+) mice, with essentially no infiltrating
      leukocytes. In contrast, electron microscopy revealed severe podocyte fusion in
      the Daf1(-/-) mice but only mild focal changes in the controls.
      Immunohistochemical staining showed equivalent deposition of the administered
      (sheep) NTS IgG in the Daf1(-/-) and Daf1(+/+) animals. This contrasted with
      marked deposition of autologous murine C3 in the former and minimal deposition in
      the latter. The results show that DAF is essential physiologically for protecting
      glomeruli against autologous complement attack initiated by the classical
      pathway.

PMID- 12003998
TI  - Pathogenic roles of tumor necrosis factor receptor p55-mediated signals in
      dimethylnitrosamine-induced murine liver fibrosis.
AB  - TNF-alpha has pleiotropic functions, but its role in liver fibrosis has not yet
      been clarified. To understand the pathophysiologic role of the TNF-alpha/TNF
      receptor (TNFR) p55 signals in liver fibrosis, 10 mg/kg of dimethylnitrosamine, a
      specific hepatotoxicant, was administered twice a week into the peritoneal cavity
      of both TNFRp55 knock-out (KO) and wild-type mice, and the severity of fibrosis
      was monitored histologically and biochemically. In wild-type mice, histologic
      analysis demonstrated evident fibrotic changes 1 week after the initiation of
      dimethylnitrosamine administration, consistent with increased liver collagen
      contents. Concomitantly, the numbers of Kupffer cells and activated hepatic
      stellate cells (HSCs) were increased in liver tissue. On the contrary, fibrotic
      changes were attenuated and the numbers of Kupffer cells and HSCs were decreased
      in TNFRp55-KO mice. Moreover, gene expression of TNF-alpha and monocyte
      chemoattractant protein-1, which are involved in Kupffer cell activation or
      migration, was decreased in the liver of TNFRp55-KO mice. Collectively, TNFRp55
      mediated signals may regulate activation of Kupffer cells and HSCs and eventually
      enhance fibrotic process.

PMID- 12003999
TI  - Salicylate protects hearing and kidney function from cisplatin toxicity without
      compromising its oncolytic action.
AB  - Salicylate has recently been demonstrated to protect against the auditory and
      vestibular side effects of aminoglycoside antibiotics. Similarities in the toxic
      mechanisms suggest salicylate as a treatment strategy to prevent the ototoxic
      side effects of cisplatin (CDDP). We first tested protection of the inner ear in
      Wistar rats receiving a single infusion of 16 mg CDDP/kg body weight with or
      without treatment with 100 mg/kg salicylate (bid) for 5 days beginning one day
      before the CDDP infusion. Cisplatin induced a threshold shift of more than 30 dB
      (at 14 kHz; measured by auditory evoked brain stem response) that was
      significantly reduced by salicylate. We then examined the protective potential of
      salicylate on the cochlea, peripheral nerves, and kidney in a rat model of breast
      cancer--Fisher344 rats implanted with highly metastatic MTLn3 breast cancer
      cells. Animals received 3 x 5 mg CDDP/kg (given every third day), and salicylate
      was administered at 100 mg/kg (bid) from 2 days before to 3 days after CDDP
      treatment. Salicylate significantly attenuated the CDDP-induced threshold shift
      from approximately 20 dB (at 16 and 24 kHz) to approximately 5 dB, and
      drastically reduced the loss of cochlear outer hair cells. Likewise, salicylate
      protected kidney function (measured as plasma blood urea nitrogen and creatinine
      levels) from CDDP toxicity. Protection of nerve conduction velocities of both
      sensory and motor nerves was minimal. The chemotherapeutic efficacy of CDDP on
      suppression of tumor mass and cancer cell metastasis remained unaffected by
      salicylate. The results suggest that administration of salicylate may become the
      basis of an effective therapeutic intervention against the ototoxic and
      nephrotoxic side effects associated with CDDP chemotherapy.

PMID- 12004000
TI  - Nitric oxide supplementation ameliorates dextran sulfate sodium-induced colitis
      in mice.
AB  - Nitric oxide (NO) synthesis is up-regulated in inflammatory bowel disease.
      However, its role in the pathophysiology of this condition is controversial. The
      aims of this study were to assess whether nitric oxide administration ameliorates
      experimental colitis and to determine the possible mechanisms underlying its
      effects on intestinal inflammation. For this purpose, the NO donor diethylamine
      NONOate (DETA/NO; 0.01, 0.1, 1, 5, or 10 mg/kg/day), or the DETA moiety, was
      administered daily to mice with dextran sulfate sodium-induced colitis. Daily
      body weight and colonic pathologic alterations at Day 10 were determined.
      Leukocyte endothelial cell interactions in colonic venules were assessed with
      intravital microscopy, and expression of endothelial cell adhesion molecules was
      determined using radiolabeled antibodies. IL-12 and IFN-gamma production were
      measured in intestinal tissue. Colitis induced a significant loss of body weight,
      reduction of colon length, and increase in colon weight and myeloperoxidase
      activity. Administration of 1 mg/kg/day DETA/NO significantly attenuated these
      pathologic changes. The marked increase in leukocyte rolling and adhesion in
      colonic venules of colitic mice were significantly reduced by administration of 1
      mg/kg/day DETA/NO. Development of colitis was associated with a marked increase
      in endothelial expression of intercellular adhesion molecule-1, vascular cell
      adhesion molecule-1, and P-selectin. Supplementation with NO significantly
      attenuated the up-regulation of endothelial intercellular adhesion molecule-1 and
      P-selectin, but not vascular cell adhesion molecule-1, in colonic tissue. NO
      abrogated the increase in IL-12 and IFN-gamma mRNA expression in the colon of
      colitic mice. The DETA moiety alone did not have any effect on any of the
      parameters studied. In conclusion, exogenous NO supplementation significantly
      ameliorates dextran sulfate sodium-induced colitis. This effect is related to a
      reduction in leukocyte recruitment and proinflammatory cytokine production.

PMID- 12004001
TI  - Lack of SYT-SSX fusion transcripts in malignant peripheral nerve sheath tumors on
      RT-PCR analysis of 34 archival cases.
AB  - The translocation t(X;18) is currently regarded as a specific molecular marker of
      synovial sarcoma (SS). Recently, however, it has been reported that malignant
      peripheral nerve sheath tumors expressed this marker in 75% of the cases. To test
      independently this iconoclastic claim, a molecular analysis for the detection of
      the SYT-SSX fusion genes was carried out using archival material of 34
      consecutive cases diagnosed as malignant peripheral nerve sheath tumors and
      treated in our Institute from 1998 to 2000. In four of these cases, the molecular
      analysis on fixed tissues was supplemented with an analysis on fresh frozen
      tissue. RNA extracted from formalin-fixed paraffin-embedded tissue blocks was
      evaluated for the presence of SYT-SSX1 and SYT-SSX2 fusion transcripts by RT-PCR.
      This analysis was extended to a wide variety of normal tissues simultaneously
      extracted and equally processed. Only two of the cases studied harbored SYT-SSX1
      and SYT-SSX2 fusion transcripts, respectively. The diagnostic reevaluation of
      these two cases in light of the molecular data disclosed that one had the
      features of a monophasic SS and the other was compatible with that entity. Both
      of these tumors were strongly immunoreactive for bcl-2, confirming the diagnostic
      utility of this marker in this instance. Our results reaffirm the specificity of
      SYT-SSX for SS and suggest that an opposite claim made in a recent study may have
      been due to a faulty interpretation of the molecular results caused by a
      contamination of the samples.

PMID- 12004002
TI  - Cellular retinol-binding protein-1 expression and modulation during in vivo and
      in vitro myofibroblastic differentiation of rat hepatic stellate cells and portal
      fibroblasts.
AB  - Cellular retinol-binding protein-1 (CRBP-1) is involved in vitamin A metabolism
      because it mediates both retinol esterification to retinyl esters and retinol
      oxidation to retinal and retinoic acid. CRBP-1 is highly expressed in the liver,
      particularly in hepatic stellate cells (HSC). In this study, we investigated the
      liver expression of CRBP-1 during experimental fibrogenesis. We also studied the
      regulation of CRBP-1 expression in cultured HSC and portal fibroblasts, two
      fibroblastic cell types involved in liver fibrogenesis. Fibrosis was induced in
      rats by carbon tetrachloride (CCl(4)) or bile duct ligation. Immunohistochemical
      staining was performed for CRBP-1 and alpha-smooth muscle (SM) actin, an
      activation marker of fibrogenic cells. CRBP-1 and alpha-SM actin expression was
      studied by Western blotting and/or Northern blot in primary cultures of HSC
      isolated by conventional methods and in portal fibroblasts that were obtained by
      outgrowth from the biliary tree after enzymatic digestion. In normal liver,
      contrary to HSC, portal fibroblasts did not express CRBP-1. After CCl(4) injury,
      CRBP-1 expression was maintained in myofibroblastic alpha-SM actin-positive HSC.
      After bile duct ligation, portal fibroblasts (which proliferated around ductular
      structures) acquired expression of both CRBP-1 and alpha-SM actin. During HSC
      activation in culture, CRBP-1 expression gradually increased until Day 5 when
      alpha-SM actin expression was obvious. Cultured portal fibroblasts developed both
      CRBP-1 and alpha-SM actin expression. In both cell populations, transforming
      growth factor-beta 1 treatment increased CRBP-1 expression. Thus, in normal
      liver, CRBP-1 expression was different among fibroblastic cells, a finding that
      adds to the concept of heterogeneity of liver fibrogenic cells. Furthermore,
      during myofibroblastic differentiation, HSC that lost their stores of retinol
      maintained a high level of CRBP-1 expression, whereas portal fibroblasts acquired
      CRBP1 expression. Together, these data suggest a correlation between CRBP-1
      expression and myofibroblastic differentiation.

PMID- 12004003
TI  - Amplification and overexpression of Elongin C gene discovered in prostate cancer
      by cDNA microarrays.
AB  - Functional significance of several oncogenes is mediated by overexpression. To
      identify overexpressed genes in prostate cancer, we analyzed expression of 1081
      transcripts in three prostate cancer cell lines (PC-3, DU145, and LNCaP) using
      cDNA microarray hybridization. The cDNA microarray analyses were validated by
      quantitative real-time RT-PCR. On average, 64% of the genes were expressed at
      detectable levels in the cell lines. Next, the expression profiles were combined
      with the data on DNA sequence copy number alterations in the cell lines obtained
      by comparative genomic hybridization. The genes for Elongin C and urokinase type
      plasminogen-activator, both located in the regions of amplification in the PC-3
      cell line (8q21 and 10q22, respectively), were found to be overexpressed in the
      PC-3. Amplification and overexpression of urokinase type plasminogen-activator in
      prostate cancer has previously been reported. Here, fluorescence in situ
      hybridization on tissue microarray showed high-level amplification of the Elongin
      C gene in 8 (23%) of 35 hormone-refractory carcinomas but in none of the
      untreated prostate carcinomas (n = 35). Finally, it was shown that the Elongin C
      gene was overexpressed and amplified also in breast cancer cell line SK-Br-3. The
      results indicate that Elongin C is a putative target gene for 8q amplification.

PMID- 12004004
TI  - Alteration of the LRP1B gene region is associated with high grade of urothelial
      cancer.
AB  - We have delineated regions of interest at chromosome 2q21.2, 2q36.3, and 2q37.1
      by deletion mapping of 114 urothelial cancers (UC). Altogether, 17%, 18%, and 63%
      of the G1, G2, and G3 tumors displayed loss of heterozygosity at chromosome 2q,
      respectively, The region at 2q21.2 was narrowed down to the LRP1B gene
      (NT_005129.6). Hemi- and homozygous deletion at the LRP1B gene region was seen in
      31 of 114 UCs. Only 8% of the UCs with G1 and none with G2 tumors showed loss of
      heterozygosity at the LRP1B gene, whereas 49% of the G3 UCs had allelic loss at
      this region. RT-PCR analysis of the LRP1B gene showed the lack of expression of
      several exons in 2 of 9 cases analyzed. Our analysis suggests that the LRP1B gene
      is a candidate tumor suppressor gene in UCs.

PMID- 12004005
TI  - Arpp, a new homolog of carp, is preferentially expressed in type 1 skeletal
      muscle fibers and is markedly induced by denervation.
AB  - In this study, we isolated and characterized a murine counterpart of the human
      Arpp (hArpp) gene. Sequence analysis revealed that the murine Arpp (mArpp) gene
      is almost identical to the Ankrd2 gene, which has recently been isolated as a
      mouse gene induced in stretched skeletal muscle. The mArpp gene encodes a protein
      of 332 amino acids that contains four well-conserved ankyrin-repeat domains in
      the central portion of the protein. The amino acid sequence of mArpp protein
      (mArpp) is highly homologous to that of mouse cardiac-restricted ankyrin-repeat
      protein (Carp), which is proposed to be a putative genetic marker for cardiac
      hypertrophy. Immunohistochemical analysis revealed that mArpp is preferentially
      expressed in type 1 skeletal muscle fibers, and that mArpp is localized in both
      the nucleus and the sarcomeric I-band of muscle fibers, suggesting that Arpp may
      function as a nuclear and sarcomeric protein. Furthermore, mArpp was also
      expressed in neurons of the cerebellum and cerebrum, the islets of Langerhans in
      the pancreas, and the esophageal epithelium, suggesting that mArpp may play a
      functional physiologic role in brain, pancreas, and esophagus as well as in type
      1 muscle fibers. Interestingly, although mArpp was localized in both nucleus and
      cytoplasm in neurons, its localization was restricted to nucleus in pancreas and
      esophagus, suggesting that intracellular localization of mArpp is regulated in a
      tissue-specific manner. Furthermore, we found that mArpp- and Carp-expression in
      skeletal muscle were markedly up-regulated after denervation. Although the
      elevated expression level of Carp was kept only for two weeks after denervation,
      that of Arpp was kept at least for 4 weeks, suggesting that mArpp and Carp may
      play distinct functional roles in denervated skeletal muscle.

PMID- 12004006
TI  - Nanotechnology in early detection of cancer.

PMID- 12004007
TI  - Conventional and molecular cytogenetic characterization of a new human cell line,
      GIST-T1, established from gastrointestinal stromal tumor.

PMID- 12004008
TI  - A Sample-saving preparation to extract DNA-binding proteins from cardiac and
      vascular tissues.

PMID- 12004009
TI  - The need to account for patient activity when evaluating the results of total hip
      arthroplasty with survivorship analysis.

PMID- 12004010
TI  - Surgical treatment of traumatic anterior shoulder instability in american
      football players.
AB  - BACKGROUND: American football players have been reported to be at high risk for
      postoperative instability after arthroscopic stabilization of anterior shoulder
      instability. While some authors have recommended open methods of stabilization in
      athletes who play contact sports, there are few data in the literature showing
      more favorable results with use of an open technique. We reviewed the results of
      an open technique of anterior shoulder stabilization in fifty-eight American
      football players after a minimum of two years of follow-up. METHODS: Fifty-eight
      American football players underwent open stabilization with use of a standardized
      technique for the treatment of recurrent anterior shoulder instability. Forty
      seven patients had recurrent dislocations, and the remaining eleven had recurrent
      subluxations. The average age of the patients was 18.2 years, and the average
      duration of follow-up was thirty-seven months. Patients were evaluated according
      to the shoulder scoring system of the American Shoulder and Elbow Surgeons and
      with use of the shoulder instability score described by Rowe and Zarins. RESULTS:
      There were no postoperative dislocations. Postoperative subluxation occurred in
      two patients, neither of whom had had a dislocation prior to the operation.
      Forward flexion and external rotation returned to within 5  of those of the
      contralateral shoulder in forty-nine patients. The average score according to the
      system of the American Shoulder and Elbow Surgeons was 97.0 points, and the
      average Rowe and Zarins score was 93.6 points. Fifty-five patients had a good or
      excellent result, and fifty-two of the fifty-eight returned to playing football
      for at least one year. One patient was forced to stop playing because of
      recurrent instability. CONCLUSIONS: Open stabilization is a predictable method of
      restoring shoulder stability in American football players while maintaining a
      range of motion approximating that found after arthroscopic stabilization.
      Postoperative stability appears to be superior to that reported after
      arthroscopic techniques in this population of patients.

PMID- 12004011
TI  - Comparison of anterior and posterior iliac crest bone grafts in terms of harvest
      site morbidity and functional outcomes.
AB  - BACKGROUND: Previous studies have demonstrated high complication rates after
      harvest of iliac crest bone grafts. This study was undertaken to compare the
      morbidity related to the harvest of anterior iliac crest bone graft with that
      related to the harvest of posterior iliac crest bone graft and to determine
      differences in functional outcome. METHODS: The medical records of eighty-eight
      consecutive patients who had undergone a total of 108 iliac crest bone-grafting
      procedures for the treatment of chronic osteomyelitis from 1991 to 1998 were
      retrospectively reviewed. Demographic characteristics, the location of the
      harvest, the volume of bone graft that was harvested, the estimated blood loss,
      and postoperative complications were recorded. Fifty-eight patients completed a
      questionnaire pertaining to postoperative and residual pain, sensory
      disturbances, functional limitations, cosmetic appearance, and overall
      satisfaction with the bone-graft harvesting procedure. RESULTS: Sixty-six
      anterior and forty-two posterior bone-graft harvest sites were evaluated at a
      minimum of two years after the operation. A major complication was associated
      with 8% (five) of the sixty-six anterior sites and 2% (one) of the forty-two
      posterior sites. The rates of minor complications were 15% (ten) and 0%,
      respectively. In the series as a whole, there were ten minor complications (9%)
      and six major complications (6%). The rates of both minor complications (p =
      0.006) and all complications (p = 0.004) were significantly higher after the
      anterior harvest procedures than they were after the posterior procedures. The
      postoperative pain at the donor site was significantly more severe (p = 0.0016)
      and of significantly greater duration (p = 0.0017) after the anterior harvests.
      No patient reported functional limitations at the latest follow-up evaluation.
      CONCLUSIONS: In this series, the complication rate was lower than those
      previously reported by other investigators. Harvest of a posterior iliac crest
      bone graft was associated with a significantly lower risk of postoperative
      complications. On the basis of the results of this study, we recommend that iliac
      crest bone graft be harvested posteriorly whenever possible.

PMID- 12004012
TI  - In situ fixation of pelvic nonunions following pathologic and insufficiency
      fractures.
AB  - BACKGROUND: A nonunion of the pelvic ring after a pathologic or insufficiency
      fracture of osteopenic bone is rare. The purpose of the present study was to
      evaluate the radiographic and clinical results of in situ fixation of these
      nonunions. METHODS: The records of forty-four patients who had been managed with
      in situ fixation of pelvic fracture nonunions were reviewed retrospectively.
      Twenty-seven patients had sustained pathologic fractures after a simple fall, and
      seventeen had sustained insufficiency fractures. Forty-two of the forty-four
      nonunions were unstable and were located unilaterally or bilaterally in the
      posterior pelvic arch, and thirty-six involved the lateral aspect of the sacrum.
      Two of the forty-four non-unions involved only the pubic rami. The average age of
      the patients was sixty-six years (range, thirty-five to eighty-seven years), and
      the average duration of postoperative follow-up was four years (range, two to
      eleven years). All patients were assessed with regard to fracture union, residual
      pelvic pain, pelvic instability, and functional status. In addition, all patients
      were asked to rate the surgical result as highly satisfactory, satisfactory, or
      unsatisfactory. RESULTS: Thirty-six (82%) of the forty-four nonunions healed
      after in situ fixation, and seven of the eight persistent nonunions healed after
      additional surgery. Thirteen patients (30%), including five patients who had
      radiographic evidence of union, had persistent pain at the one-year follow-up
      assessment. None of the forty-three patients in whom the fractures eventually
      healed complained of persistent pelvic instability. At the time of the final
      follow-up examination, twenty-four patients (55%) were highly satisfied, twelve
      (27%) were satisfied, and eight (18%) were unsatisfied with the surgical result.
      CONCLUSIONS: In situ fixation of a nonunion of the pelvic ring following a
      pathologic or insufficiency fracture can result in a decrease in pelvic pain and
      instability along with an improvement in walking ability. A high percentage of
      patients complain of persistent pain, even if there is radiographic evidence of
      union of the pelvic ring.

PMID- 12004013
TI  - Survival and polyethylene wear of porous-coated acetabular components in patients
      less than fifty years old: results at nine to fourteen years.
AB  - BACKGROUND: Younger patients (those who are less than fifty years old) have been
      shown to have a high rate of failure of cemented acetabular components following
      total hip arthroplasty. In this report, we present the results associated with
      the use of an uncemented acetabular component in young patients who were
      evaluated at a minimum of nine years postoperatively. METHODS: Between December
      1984 and December 1989, the senior author performed 174 primary total hip
      arthroplasties with use of a single design of porous-coated acetabular component.
      Seventy-one of these procedures were performed in fifty-six patients who were
      younger than fifty years old. Fifty-six of the seventy-one hips were available
      for radiographic and clinical analysis after a mean duration of follow-up of
      eleven years. All hips had been treated with a Harris-Galante-I porous-coated
      acetabular component that had been placed with a line-to-line fit and fixed with
      a mean of four screws. Clinical analysis was performed with use of the Harris hip
      score. Standardized anteroposterior radiographs were analyzed with regard to
      migration, radiolucent lines, pelvic osteolysis, and two-dimensional linear wear
      of the polyethylene. RESULTS: No metal shell was revised because of aseptic
      loosening, and no shell was loose at the time of the latest follow-up. A
      nonprogressive radiolucent line was seen in one zone in ten hips (18%) and in two
      zones in six hips (11%). No hip had a radiolucent line in all three zones. Pelvic
      osteolysis was noted in thirteen hips (23%); the osteolysis was observed in the
      ischium in eleven hips and around the screws in two. Survivorship analysis
      revealed that the probability of survival of the metal shell was 98% (95%
      confidence interval, 96.9% to 99.9%) at ten years. The mean rate of linear
      polyethylene wear (and standard deviation) was 0.15 +/- 0.10 mm/yr (range, 0.02
      to 0.59 mm/yr). The wear rate was significantly increased in patients with an
      excellent Harris hip score (p = 0.004) and a younger age (less than thirty-eight
      years) (p = 0.026). With the numbers available, no relationship could be detected
      between the wear rate and the gender or weight of the patient, the polyethylene
      thickness, the abduction angle, or the femoral neck length. CONCLUSIONS: The
      fixation and survival of porous-coated acetabular metal shells in patients less
      than fifty years old was excellent after a mean duration of follow-up of eleven
      years. The high rate of linear polyethylene wear and the high prevalence of
      pelvic osteolysis are of serious concern in this patient population. Continued
      follow-up will be necessary to evaluate the influence of these findings on the
      longevity of the fixation of this prosthesis.

PMID- 12004014
TI  - Ankle and knee coupling in patients with spastic diplegia: effects of
      gastrocnemius-soleus lengthening.
AB  - BACKGROUND: Empirical observations of subjects with an equinus gait have
      suggested that there is coupled motion between the ankle and knee such that,
      during single-limb stance, the ankle moves into equinus as the knee extends.
      Since the gastrocnemius-soleus muscle-tendon unit spans both joints, we
      hypothesized that this muscle-tendon unit may be responsible for the coupling and
      that lengthening of the gastrocnemius-soleus muscle alone would result in greater
      ankle dorsiflexion as well as greater knee extension in single-limb stance,
      effectively uncoupling these joints. The concept that gastrocnemius-soleus
      lengthening may promote knee extension is counter to the popular notion that
      crouch gait may result if the hamstrings are not lengthened concomitantly.
      METHODS: A retrospective review identified thirty-four subjects with specific
      kinematic characteristics of equinus gait, and their gait was compared with that
      of normal children. Of the thirty-four subjects, eleven (twenty-two limbs)
      subsequently underwent isolated midcalf lengthening of the gastrocnemius and
      soleus muscles with use of a recession technique. Gait analysis including joint
      kinematics and joint kinetics, electromyography, and physical examination were
      performed to test the hypothesis. RESULTS: We found that, unlike the normal
      subjects, the patients with an equinus gait pattern had a positive correlation (r
      = 0.7) between ankle and knee motion during single-limb stance. As hypothesized,
      ankle plantar flexion occurred while the knee moved into extension during single
      limb stance. Calculations of the lengths of the gastrocnemius-soleus muscle
      tendon units showed them to be short throughout the gait cycle (p < 0.0001).
      After gastrocnemius-soleus recession, peak ankle dorsiflexion (p < 0.001) and
      peak ankle power (p < 0.001) shifted to occur later in stance than they did in
      the preoperative gait cycle. Furthermore, the magnitude of peak power increased
      (p < 0.001) in late stance despite the added length of the gastrocnemius-soleus
      muscle-tendon unit. The electromyographic amplitude of the gastrocnemius-soleus
      was reduced during loading (p < 0.02), and this finding, together with the
      kinetic changes, suggested that muscle tension was reduced. Changes at the knee
      were less pronounced but included greater knee extension at foot contact (p <
      0.01). No increase in the knee flexion angle or extension moment occurred in
      midstance after the surgery. CONCLUSIONS: Patients with an equinus gait pattern
      function with a shortened gastrocnemius-soleus muscle-tendon unit, and this
      results in coupled motion between the ankle and knee during single-limb stance.
      Lengthening, with use of a recession technique, shifted ankle power generation
      and dorsiflexion to a later time in stance with no tendency to increase midstance
      knee flexion. Knee extension did increase at foot contact, but excessive
      midstance knee flexion persisted and was likely due to concomitant contracture of
      the hamstrings.

PMID- 12004015
TI  - Proximal radial resection for posttraumatic radioulnar synostosis: a new
      technique to improve forearm rotation.
AB  - BACKGROUND: Heterotopic ossification about the elbow joint can lead to
      considerable functional disability, including the loss of forearm rotation. Many
      procedures have been described for the treatment of proximal radioulnar
      synostosis. Varying degrees of success have been achieved with regard to the
      improvement of the flexion arc, but less success has been reported in terms of
      the restoration of forearm rotation. The success of treatment is associated with
      the extent of heterotopic ossification, soft-tissue scarring, and anatomical
      distortion. A new and simple technique to address the unresectable proximal
      radioulnar synostosis is described. METHODS: Seven patients were managed with a
      partial proximal radial resection distal to the synostosis and were followed for
      an average of eighty months (range, twenty-four to 144 months). RESULTS: Forearm
      rotation improved from an average fixed pronation of 5 degrees to an average arc
      of 98 degrees (range, 40 degrees to 175 degrees ). The average functional score
      improved from 57 points preoperatively to 81 points at the time of the final
      review. Complications included reankylosis at the site of the resection and ulnar
      nerve sensory neurapraxia in one patient each. CONCLUSIONS: Resection of a 1-cm
      thick section of the proximal part of the radial shaft provides a safe and
      reliable method of improving forearm rotation in patients with heterotopic
      ossification of the elbow. A single technical factor that seems to positively
      influence the result is the application of bone wax at the resection site. This
      simple procedure is ideally suited for patients who have a proximal radioulnar
      synostosis that (1) is too extensive to allow a safe and discrete resection, (2)
      involves the articular surface, and (3) is associated with an anatomical
      deformity.

PMID- 12004016
TI  - Results of operative treatment of fractures of the posterior wall of the
      acetabulum.
AB  - BACKGROUND: The purpose of this study was to determine the clinical outcome in
      patients in whom a displaced fracture of the posterior wall of the acetabulum had
      been treated by open reduction and internal fixation. METHODS: One hundred
      patients who had had open reduction and internal fixation of an unstable
      unilateral fracture of the posterior wall of the acetabulum were studied. Ninety
      four patients were assessed at a mean of five years (range, two to fourteen
      years) after the injury. Six patients with a poor result were followed for less
      than two years. The functional outcome was evaluated with use of the clinical
      grading system adopted by Letournel and Judet with incorporation of modifications
      by Matta. Patient, fracture, and radiographic variables were analyzed to identify
      possible associations with functional outcome. RESULTS: The reduction of the
      fracture, as determined with plain radiography, was graded as anatomic in ninety
      seven patients and as imperfect in three. The clinical outcome at the time of
      final follow-up was graded as excellent in fifty-five patients, very good in
      twenty-five, good in nine, fair in one, and poor in ten. The radiographic result
      was excellent in eighty-one patients, good in five, fair in four, and poor in
      ten. There was a strong association between the clinical outcome and the final
      radiographic grade. Variables identified as risk factors for an unsatisfactory
      clinical result included a delay of greater than twelve hours before reduction of
      an associated hip dislocation, an age of fifty-five years or older at the time of
      injury, intra-articular comminution, and osteonecrosis. CONCLUSIONS: The
      uncomplicated radiographic appearance and relatively simple operative approach
      for fractures of the posterior acetabular wall belie the risk of poor results.
      Prompt reduction of an associated hip dislocation is imperative. Fractures in
      elderly patients and those with extensive comminution are more likely to have a
      poor clinical result. However, a high likelihood of a long-term good-to-excellent
      result can be expected following anatomic reduction and internal fixation of
      these fractures.

PMID- 12004017
TI  - Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective,
      randomized study of three hundred and forty knees.
AB  - BACKGROUND: A prospective, randomized study was conducted to evaluate the
      efficacy of cefuroxime-impregnated cement in the prevention of deep infection
      after primary total knee arthroplasties performed without so-called clean-air
      measures, such as laminar flow and body-exhaust suits. METHODS: Three hundred and
      forty primary total knee arthroplasties were performed with cementless fixation
      of the femoral component and cement fixation of the patellar and tibial
      components. The knees were randomly divided into two groups. In Group 1 (178
      knees), cefuroxime-impregnated cement was used for fixation, whereas in Group 2
      (162 knees), the cement did not contain cefuroxime. There was no significant
      difference between the two groups regarding demographic variables, the
      preoperative or postoperative knee score, the duration of the operation or of the
      use of the tourniquet, or the amount of blood transfused perioperatively. The
      average duration of follow-up was forty-nine months (range, twenty-six to eighty
      months). RESULTS: No deep infection developed in the 178 knees in Group 1,
      whereas a deep infection developed in five (3.1%) of the 162 knees in Group 2 (p
      = 0.0238). Two superficial wound infections developed in each group. CONCLUSIONS:
      Cefuroxime-impregnated cement was shown to be effective in the prevention of
      early to intermediate deep infection after primary total knee arthroplasty
      performed with use of perioperative systemic antibiotic prophylaxis but no so
      called clean-air measures.

PMID- 12004018
TI  - Posterior ankle arthroscopy: an anatomic study.
AB  - BACKGROUND: Ankle arthroscopy has generally been performed with use of anterior
      portals with the patient in the supine position. Little has been published on
      ankle arthroscopy performed with use of posterior portals, particularly with the
      patient in the prone position. The purpose of the present study was to evaluate
      the relative safety and efficacy of ankle arthroscopy with use of posterior
      portals with the limb in the prone position. METHODS: Thirteen fresh-frozen
      cadaver specimens were used. Posterolateral and posteromedial portals were
      established. Arthroscopy was performed, and the extent of the talar dome that
      could be visualized was marked. Four-millimeter plastic cannulae were filled with
      oil and were placed in the portals for use as reference landmarks on magnetic
      resonance imaging studies. The proximity of the portal cannulae to the adjacent
      structures was measured on standard magnetic resonance images and then during
      careful dissection. The distances measured by dissection were compared with the
      measurements made on magnetic resonance images. RESULTS: An average of 54%
      (range, 42% to 73%) of the talar dome could be visualized. The average distance
      between a cannula and adjacent anatomic structures after dissection was 3.2 mm
      (range, 0 to 8.9 mm) to the sural nerve, 4.8 mm (range, 0 to 11.0 mm) to the
      small saphenous vein, 6.4 mm (range, 0 to 16.2 mm) to the tibial nerve, 9.6 mm
      (range, 2.4 to 20.1 mm) to the posterior tibial artery, 17 mm (range, 19 to 31
      mm) to the medial calcaneal nerve, and 2.7 mm (range, 0 to 11.2 mm) to the flexor
      hallucis longus tendon. The magnetic resonance images demonstrated very similar
      distances except in the case of the distance between the posteromedial cannula
      and the tibial nerve, which often was difficult to specifically identify on
      magnetic resonance imaging studies. CONCLUSIONS: The findings of the present
      cadaveric study suggest that, with the patient in the prone position,
      arthroscopic equipment may be introduced into the posterior aspect of the ankle
      without gross injury to the posterior neurovascular structures. Limited clinical
      trials should be carried out to confirm this finding.

PMID- 12004019
TI  - Total hip replacement with a cementless acetabular component and a cemented
      femoral component in patients younger than fifty years of age.
AB  - BACKGROUND: We have been using hybrid total hip arthroplasty (a cementless
      acetabular component and a cemented stem) in young patients. The purpose of this
      study was to determine the prevalence of aseptic loosening, polyethylene wear,
      and osteolysis after the use of this technique. METHODS: We studied a prospective
      consecutive series of sixty-four primary hybrid total hip replacements in fifty
      five patients younger than fifty years old. There were forty-three men and twelve
      women; the average age at the time of the index operation was 43.4 years. The
      average duration of follow-up was 9.4 years. We used a cementless acetabular
      component without screw-holes and a cemented femoral component with a 22-mm head
      in all hips. Clinical follow-up with use of Harris hip ratings and radiographic
      follow-up were performed at six weeks; at three, six, and twelve months; and
      yearly thereafter. The sequential annual linear and volumetric wear rates were
      measured, and bone-remodeling and osteolysis were assessed. RESULTS: The mean
      preoperative Harris hip score was 44 points, which increased to 95 points at the
      time of final follow-up. No hip had aseptic loosening. One hip (2%) was revised
      because of late infection. The average linear wear (and standard deviation) was
      0.96 +/- 0.066 mm, with an average annual rate of 0.096 +/- 0.013 mm. The average
      volumetric wear was 364.7 +/- 25.2 mm (3), with an average annual rate of 43.4 +/
      3.5 mm (3). Six hips (9%) had an osteolytic lesion of <1 cm in diameter in the
      calcar femorale (zone 7). CONCLUSIONS: Our results show that a hybrid
      arthroplasty with a cementless acetabular component and a smooth cemented femoral
      component (Ra, 0.6 mm) is effective for primary total hip replacement in young
      patients. Although there was no aseptic loosening and a low prevalence of
      osteolysis at the latest follow-up evaluation, the high rates of linear and
      volumetric wear of the polyethylene liner in these young patients remain a
      concern.

PMID- 12004020
TI  - Scalene regional anesthesia for shoulder surgery in a community setting: an
      assessment of risk.
AB  - BACKGROUND: A retrospective review of shoulder procedures using scalene block
      anesthesia was performed. METHODS: The records of all 218 patients who had
      undergone scalene block anesthesia over a three-year period at two facilities
      were retrospectively reviewed. All blocks were performed with use of a standard
      blunt-needle technique with the patient awake and with use of preoperative nerve
      stimulation to localize the brachial plexus. RESULTS: Adjunctive general
      anesthesia was used for 179 (82%) of the 218 patients. Seventy-two patients (33%)
      required intravenous pain medication immediately on arrival in the recovery room,
      and twenty-eight blocks (13%) failed. One grand mal seizure, one episode of
      cardiovascular collapse, and four episodes of severe respiratory distress were
      noted. Two patients had temporary neurologic injuries that persisted at six
      weeks. The mean duration of the block was 9 +/- 4.6 hours. Two hundred (92%) of
      the 218 patients required parenteral narcotics despite the use of scalene block
      anesthesia. CONCLUSION: Informed consent discussions regarding scalene block
      anesthesia should include information on the prevalence of complications and the
      efficacy of the technique.

PMID- 12004021
TI  - Biomechanical comparison of effects of supraspinatus tendon detachments, tendon
      defects, and muscle retractions.
AB  - BACKGROUND: Rotator cuff ruptures are frequently associated with loss of strength
      of the shoulder. However, the characteristics of the rotator cuff tear that are
      responsible for the loss of force generation and transmission have not yet been
      identified. The purpose of this study was to compare the effects of supraspinatus
      tendon detachments, tendon defects, and muscle retractions on in vitro force
      transmission by the rotator cuff to the humerus. METHODS: The rotator cuff
      tendons from ten cadaver shoulders were loaded proportionally to the respective
      cross-sectional areas of their muscles. A fiberglass rod was cemented into the
      medullary canal of the humerus and connected to a three-component load cell for
      the measurement of the forces transmitted by the rotator cuff to the humerus.
      This study was performed with the humerus in a hanging arm position and with
      various sizes of supraspinatus tendon detachments, tendon defects, and muscle
      retractions. RESULTS: Detachment or creation of a defect involving one-third or
      two-thirds of the supraspinatus tendon resulted in a minor reduction in the force
      transmitted by the rotator cuff (< or =5%), while detachment or creation of a
      defect involving the whole tendon resulted in a moderate reduction (11% and 17%,
      respectively). Simulated muscle retraction involving one-third, two-thirds, and
      the whole tendon resulted in losses of torque measuring 19%, 36%, and 58%,
      respectively. Side-to-side repair of the one-third and two-thirds defects nearly
      restored the force transmission capability, whereas a deficit remained after side
      to-side repair following complete resection. CONCLUSIONS: Our results support the
      rotator cable concept and correspond to the clinical observation that patients
      with a small rupture of the rotator cuff may present without a loss of shoulder
      strength. Muscle retraction is potentially an important factor responsible for
      loss of shoulder strength following large rotator cuff ruptures. CLINICAL
      RELEVANCE: Supraspinatus muscle retraction diminishes glenohumeral abduction
      torque significantly more than either a defect in the tendon or a simple
      detachment of the tendon from the tuberosity. In cases of irreparable defects,
      side-to-side repair may be worthwhile to restore muscle tension and the integrity
      of the rotator cable.

PMID- 12004022
TI  - Early failure of precoated femoral components in primary total hip arthroplasty.
AB  - BACKGROUND: In an effort to decrease the rate of aseptic loosening, certain
      cemented femoral components were designed to have a roughened or textured surface
      with a methylmethacrylate precoating. Reports differ as to whether this step has
      increased or decreased the rate of failure. This study was designed to evaluate
      this issue. METHODS: Five hundred and fourteen hips treated with a cemented
      Harris Precoat stem (Zimmer, Warsaw, Indiana) were evaluated clinically and
      radiographically and compared with 254 hips treated with an uncoated Harris
      Design-2 stem (Howmedica, East Rutherford, New Jersey). Prostheses that had been
      removed at revision were examined. The cementing and surgical techniques were
      identical and the population demographics were similar for these two groups.
      RESULTS: The mean durations of follow-up were 8.4 and 13.5 years for the Precoat
      and uncoated Design-2 stems, respectively. At those times, at least forty-nine
      (9.5%) of the 514 Precoat components and at least ten (3.9%) of the 254 uncoated
      Design-2 stems had failed (p = 0.006). Five Precoat stems fractured, and no
      uncoated Design-2 stems fractured. Component failure was associated with use in
      young, active, heavy men with a diagnosis of avascular necrosis and generally
      with the use of smaller components. The cementing technique was satisfactory in
      the majority of the patients, and there were no qualitative differences in
      cementing technique between the hips that failed and those that did not. The
      mechanisms of failure of the Precoat prostheses included bone-cement loosening,
      focal osteolysis, stem fracture, and prosthesis-cement debonding. Fractures of
      smaller components occurred as a result of fatigue failure and were associated
      with good distal fixation but proximal stem loosening. CONCLUSIONS: The rate of
      failure of roughened, precoated, cemented femoral components was considerably
      higher and occurred earlier than that of femoral components that were neither
      textured nor precoated with methylmethacrylate. Younger patients with avascular
      necrosis had a higher risk of failure; however, this factor alone did not
      completely explain the differences in outcome between these two components. The
      causes of aseptic loosening are multifactorial and may be related to component
      design and size as well as to precoating and surface finish.

PMID- 12004023
TI  - Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal
      chondrogenesis in vitro: a preliminary report.
AB  - BACKGROUND: Articular cartilage has limited potential for repair. There have been
      various attempts aimed at improving the repair process in articular cartilage.
      Transforming growth factor-beta1 (TGF-beta1) has a stimulatory effect on
      chondrogenesis in periosteal explants. The purpose of the present study was to
      determine the effect of brief exposures (i.e., thirty and sixty minutes) of high
      concentrations of TGF-beta1 on periosteal chondrogenesis. METHODS: Five hundred
      and seventy-three periosteal explants were harvested from forty-six two-month-old
      male New Zealand White rabbits. Explants were exposed to 50 or 100 ng/mL of TGF
      beta1 for thirty or sixty minutes. The amount of cartilage formed was then
      determined with use of a standardized six-week agarose culture assay. RESULTS:
      There was a significant increase in the amount of cartilage formation (p < 0.01),
      Type-II collagen content (p < 0.05), and sulfate incorporation (p < 0.0001) in
      explants treated with TGF-beta1. Maximal stimulation occurred following exposure
      to 100 ng/mL of TGF-beta1 for thirty minutes. There was also an increase in
      chondrocyte proliferation as measured by [ (3) H-] thymidine incorporation on day
      5 of culture (p < 0.049). CONCLUSIONS: The findings of this study indicate that
      exposure to TGF-beta1 has a stimulatory effect on periosteal chondrogenesis. This
      stimulatory effect is observed even with a very brief exposure time of thirty
      minutes. CLINICAL RELEVANCE: A possible clinical application of these findings is
      exposure of periosteal grafts that are currently utilized clinically to resurface
      articular defects to TGF-beta1 during the short time between graft procurement
      and implantation into the joint. This may obviate the need for intra-articular
      administration of TGF-beta1 and may enhance the ultimate graft incorporation and
      quality of cartilage repair.

PMID- 12004024
TI  - Heavy metal injection granulomas: a source of diagnostic confusion : a composite
      case report.

PMID- 12004025
TI  - A modification of the McLaughlin procedure as salvage for missed locked posterior
      fracture-dislocation of the humeral head: a case report.

PMID- 12004026
TI  - Congenital hypoplasia of the ulnar nerve: a case report.

PMID- 12004027
TI  - Primary rhabdomyosarcoma of the humerus: a case report and review of the
      literature.

PMID- 12004028
TI  - Elbow stiffness following malunion of a fracture of the lateral epicondyle of the
      humerus in a child: a case report.

PMID- 12004029
TI  - Muscle injuries and repair: current trends in research.

PMID- 12004031
TI  - AOA 2001 John J. Fahey, MD, Memorial North American Traveling Fellowship:
      fellows' travel diary.

PMID- 12004032
TI  - Prevention of childhood pedestrian trauma: a study of interventions over six
      years.

PMID- 12004034
TI  - Treatment of reverse obliquity fractures of the intertrochanteric region of the
      femur.

PMID- 12004035
TI  - Classifying spinal arthrodesis in adolescent idiopathic scoliosis.

PMID- 12004036
TI  - The feasibility of a national joint replacement registry in the United States.

PMID- 12004037
TI  - Questions regarding the Swanson silicone trapezium implant.

PMID- 12004038
TI  - Immobilization of anterior and posterior glenohumeral dislocation.

PMID- 12004039
TI  - Pseudarthrosis after shoulder arthrodesis.

PMID- 12004040
TI  - Thromboprophylaxis in hip arthroplasty.

PMID- 12004041
TI  - Obtaining correct rotational alignment of the femur.

PMID- 12004042
TI  - Encouraging the development of the orthopaedic clinician-scientist.

PMID- 12004043
TI  - Risks and benefits of chemoprophylaxis.

PMID- 12004044
TI  - Intraoperative migration of the trial femoral head into the pelvis during total
      hip arthroplasty: prevention and retrieval.

PMID- 12004052
TI  - What's new in pediatric orthopaedics.

PMID- 12004053
TI  - Coupling of DNA helicase and endonuclease activities of yeast Dna2 facilitates
      Okazaki fragment processing.
AB  - Saccharomyces cerevisiae Dna2 possesses both helicase and endonuclease
      activities. Its endonuclease activity is essential and well suited to remove RNA
      DNA primers of Okazaki fragments. In contrast, its helicase activity, although
      required for optimal growth, is not essential when the rate of cell growth is
      reduced. These findings suggest that DNA unwinding activity of Dna2 plays an
      auxiliary role in Okazaki fragment processing. To address this issue, we examined
      whether the Dna2 helicase activity influenced its intrinsic endonuclease activity
      using two mutant proteins, Dna2D657A and Dna2K1080E, which contain only helicase
      or endonuclease activity, respectively. Experiments performed with a mixture of
      Dna2D657A and Dna2K1080E enzymes revealed that cleavage of a single-stranded DNA
      by endonuclease activity of Dna2 occurs while the enzyme translocates along the
      substrate. In addition, DNA unwinding activity efficiently removed the secondary
      structure formed in the flap structure, which was further aided by replication
      protein A. Our results suggest that the Dna2 unwinding activity plays a role in
      facilitating the removal of the flap DNA by its intrinsic endonuclease activity.

PMID- 12004054
TI  - Cooperation of protein kinase A and Ras/ERK signaling pathways is required for AP
      1-mediated activation of fibroblast growth factor-inducible response element
      (FiRE).
AB  - Recent studies suggest a crucial role for protein kinase A (PKA) in the
      regulation of growth factor signaling. However, the effect of PKA on the
      transcription of growth factor-responsive genes has drawn far less attention.
      Here we have investigated the signaling mechanisms involved in the activation of
      an activator protein-1 (AP-1)-driven, growth factor-specific enhancer element,
      fibroblast growth factor-inducible response element (FiRE). The activation was
      found to be mediated by three phorbol 12-O-tetradecanoate-13-acetate-response
      element-related DNA elements of FiRE, including motif 4 and two distinct elements
      of motif 5 (referred to as M5-1 and M5-2). All three elements were required for
      full FiRE activity. Stimulation of cells with fibroblast growth factor-2 (FGF-2)
      induced the binding of AP-1 to motif 4 and M5-2, whereas M5-1 did not show
      detectable binding. The FGF-2-induced FiRE activation appeared to require
      cooperational function of the Ras/ERK and PKA pathways. Inhibition of either of
      the pathways abolished the binding of AP-1 complexes to motif 4 and motif 5 and
      the subsequent FiRE activation. By contrast, costimulation of cells with FGF-2
      and the PKA activator 8-bromo-cyclic AMP increased the binding of AP-1 to FiRE
      and potentiated the level of transcriptional activity. The cooperational function
      of these two pathways was confirmed by experiments with cell lines stably
      expressing 4-hydroxytamoxifen-inducible oncogenic Raf-1 (DeltaRaf-1:ER[DD]).
      Noticeably, the induction systems showed variations with respect to regulation of
      AP-1-driven activation of FiRE. These differences were likely to originate from
      the ability of these two systems to induce the differential activation pattern of
      the Ras/ERK pathway.

PMID- 12004055
TI  - Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor
      (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid
      receptor by enhancing its recycling rate.
AB  - We have investigated whether Ezrin-radixin-moesin (ERM)-binding phosphoprotein
      50/Na(+)/H(+) exchanger regulatory factor (EBP50/NHERF), a PDZ domain-containing
      phosphoprotein, is associated with the human kappa opioid receptor (hkor) and
      whether it regulates the trafficking and signaling of the hkor. When expressed in
      CHO cells stably transfected with the FLAG-tagged hkor (FLAG-hkor), EBP50/NHERF
      co-immunoprecipitated with FLAG-hkor, and the PDZ domain I, but not the PDZ
      domain II, of EBP50/NHERF was involved in the interaction. Treatment with the
      agonist (-)-(trans)-3,4- dichloro-N-methyl-N-[2-(1
      pyrrolidiny)cyclohexyl]benzeneacetamide (U50,488H) enhanced the association of
      EBP50/NHERF with FLAG-hkor. Expression of EBP50/NHERF, but not a truncated form
      lacking the ERM-binding domain, abolished U50,488H-induced down-regulation of
      FLAG-hkor, which was apparently due to an increase in the recycling rate of
      internalized receptors. However, expression of EBP50/NHERF did not affect
      U50,488H binding affinity and U50,488H-stimulated [(35)S]guanosine 5'-3-O
      (thio)triphosphate binding and p42/p44 MAP kinase activation, nor did it affect
      U50,488H-induced desensitization and internalization of FLAG-hkor. To determine
      the motif of FLAG-hkor involved in EBP50/NHERF binding, we generated two mutants,
      FLAG-hkor-A and FLAG-hkor-EE, in which one Ala or two Glu residues were added to
      the C terminus, respectively. Neither FLAG-hkor-A nor FLAG-hkor-EE co
      immunoprecipitated with EBP50/NHERF, and U50,488H-induced down-regulation of FLAG
      hkor-A and FLAG-hkor-EE were not affected by expression of EBP50/NHERF. Thus,
      EBP50/NHERF binds to the C terminus of FLAG-hkor and blocks the down-regulation
      of FLAG-hkor. The C-terminal sequence of the hkor, NKPV, is distinctly different
      from the sequence D(S/T)XL, the optimal C-terminal motif in the beta(2)
      adrenergic receptor for EBP50/NHERF binding. EBP50/NHERF may have a broader
      binding specificity and may interact with a subset of G protein-coupled receptors
      to serve as a recycling signal for these receptors.

PMID- 12004056
TI  - Increased basal cAMP-dependent protein kinase activity inhibits the formation of
      mesoderm-derived structures in the developing mouse embryo.
AB  - A targeted disruption of the RIalpha isoform of protein kinase A (PKA) was
      created by using homologous recombination in embryonic stem cells. Unlike the
      other regulatory and catalytic subunits of PKA, RIalpha is the only isoform that
      is essential for early embryonic development. RIalpha homozygous mutant embryos
      fail to develop a functional heart tube at E8.5 and are resorbed at approximately
      E10.5. Mutant embryos show significant growth retardation and developmental delay
      compared with wild type littermates from E7.5 to E10.5. The anterior-posterior
      axis of RIalpha mutants is well developed, with a prominent head structure but a
      reduced trunk. PKA activity measurements reveal an increased basal PKA activity
      in these embryos. Brachyury mRNA expression in the primitive streak of RIalpha
      mutants is significantly reduced, consistent with later deficits in axial,
      paraxial, and lateral plate mesodermal derivatives. This defect in the production
      and migration of mesoderm can be completely rescued by crossing RIalpha mutants
      to mice carrying a targeted disruption in the Calpha catalytic subunit,
      demonstrating that unregulated PKA activity rather than a specific loss of
      RIalpha is responsible for the phenotype. Primary embryonic fibroblasts from
      RIalpha mutant embryos display an abnormal cytoskeleton and an altered ability to
      migrate in cell culture. Our results demonstrate that unregulated PKA activity
      negatively affects growth factor-mediated mesoderm formation during early mouse
      development.

PMID- 12004057
TI  - Complex pattern of membrane type 1 matrix metalloproteinase shedding. Regulation
      by autocatalytic cells surface inactivation of active enzyme.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane MMP
      shown to play a critical role in normal development and in malignant processes.
      Emerging evidence indicates that MT1-MMP is regulated by a process of ectodomain
      shedding. Active MT1-MMP undergoes autocatalytic processing on the cell surface,
      leading to the formation of an inactive 44-kDa fragment and release of the entire
      catalytic domain. Analysis of the released MT1-MMP forms in various cell types
      revealed a complex pattern of shedding involving two major fragments of 50 and 18
      kDa and two minor species of 56 and 31-35 kDa. Protease inhibitor studies and a
      catalytically inactive MT1-MMP mutant revealed both autocatalytic (18 kDa) and
      non-autocatalytic (56, 50, and 31-35 kDa) shedding mechanisms. Purification and
      sequencing of the 18-kDa fragment indicated that it extends from Tyr(112) to
      Ala(255). Structural and sequencing data indicate that shedding of the 18-kDa
      fragment is initiated at the Gly(284)-Gly(285) site, followed by cleavage between
      the conserved Ala(255) and Ile(256) residues near the conserved methionine turn,
      a structural feature of the catalytic domain of all MMPs. Consistently, a
      recombinant 18-kDa fragment had no catalytic activity and did not bind TIMP-2.
      Thus, autocatalytic shedding evolved as a specific mechanism to terminate MT1-MMP
      activity on the cell surface by disrupting enzyme integrity at a vital structural
      site. In contrast, functional data suggest that the non-autocatalytic shedding
      generates soluble active MT1-MMP species capable of binding TIMP-2. These studies
      suggest that ectodomain shedding regulates the pericellular and extracellular
      activities of MT1-MMP through a delicate balance of active and inactive enzyme
      soluble fragments.

PMID- 12004058
TI  - The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X
      receptor confer the receptor with high sensitivity to chenodeoxycholate.
AB  - The critical steps in bile acid metabolism have remarkable differences between
      humans and mice. It is known that human cholesterol 7 alpha-hydroxylase, the
      enzyme catalyzing the rate-limiting step of bile acid synthesis, is more
      sensitive to bile acid suppression. In addition, hepatic bile acid export in
      humans is more dependent on the bile salt export pump (BSEP). To explore the
      molecular basis for these species differences, we analyzed the function of the
      ligand-binding domain (LBD) of human and murine farnesoid X receptor (FXR), a
      nuclear receptor for bile acids. We observed a strong interspecies difference in
      bile acid-mediated FXR function; in the coactivator association assay,
      chenodeoxycholate (CDCA) activated human FXR-LBD with 10-fold higher affinity and
      3-fold higher maximum response than murine FXR-LBD. Consistently, in HepG2 cells
      human FXR-LBD increased reporter expression more robustly in the presence of
      CDCA. The basis for these differences was investigated by preparing chimeric
      receptors and by site-directed mutagenesis. Remarkably, the double replacements
      of Lys(366) and Val(384) in murine FXR (corresponding to Asn(354) and Ile(372) in
      human FXR) with Asn(366) and Ile(384) explained the difference in both potency
      and maximum activation; compared with the wild-type murine FXR-LBD, the double
      mutant gained 8-fold affinity and more than 250% maximum response to CDCA in
      vitro. This mutant also increased reporter expression to an extent comparable
      with that of human FXR-LBD in HepG2 cells. These results demonstrate that
      Asn(354) and Ile(372) are critically important for FXR function and that murine
      FXR can be "humanized" by substituting with the two corresponding residues of
      human FXR. Consistent with the difference in FXR-LBD transactivation, CDCA
      induced endogenous expression of human BSEP by 10-12-fold and murine BSEP by 2-3
      fold in primary hepatocytes. This study not only provides the identification of
      critical residues for FXR function but may also explain the species difference in
      bile acids/cholesterol metabolism.

PMID- 12004059
TI  - POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by
      interacting with the zinc finger and interfering with DNA binding activity of
      Sp1.
AB  - The POZ domain is a protein-protein interaction motif that is found in many
      transcription factors, which are important for development, oncogenesis,
      apoptosis, and transcription repression. We cloned the POZ domain transcription
      factor, FBI-1, that recognizes the cis-element (bp -38 to -22) located just
      upstream of the core Sp1 binding sites (bp -22 to +22) of the ADH5/FDH minimal
      promoter (bp -38 to +61) in vitro and in vivo, as revealed by electrophoretic
      mobility shift assay and chromatin immunoprecipitation assay. The ADH5/FDH
      minimal promoter is potently repressed by the FBI-1. Glutathione S-transferase
      fusion protein pull-down showed that the POZ domains of FBI-1, Plzf, and Bcl-6
      directly interact with the zinc finger DNA binding domain of Sp1. DNase I
      footprinting assays showed that the interaction prevents binding of Sp1 to the GC
      boxes of the ADH5/FDH promoter. Gal4-POZ domain fusions targeted proximal to the
      GC boxes repress transcription of the Gal4 upstream activator sequence-Sp1
      adenovirus major late promoter. Our data suggest that POZ domain represses
      transcription by interacting with Sp1 zinc fingers and by interfering with the
      DNA binding activity of Sp1.

PMID- 12004060
TI  - The origin recognition complex marks a replication origin in the human TOP1 gene
      promoter.
AB  - The locations of the origin recognition complex (ORC) in mammalian genomes have
      been elusive. We have therefore analyzed the DNA sequences associated with human
      ORC via in vivo cross-linking and chromatin immunoprecipitation. Antibodies
      specific for hOrc2 protein precipitate chromatin fragments that also contain
      other ORC proteins, suggesting that the proteins form multisubunit complexes on
      chromatin in vivo. A binding region for ORC was identified at the CpG island
      upstream of the human TOP1 gene. Nascent strand abundance assays show that the
      ORC binding region coincides with an origin of bidirectional replication. The
      TOP1 gene includes two well characterized matrix attachment regions. The matrix
      attachment region elements analyzed contain no ORC and constitute no sites for
      replication initiation. In initial attempts to use the chromatin
      immunoprecipitation technique for the identification of additional ORC sites in
      the human genome, we isolated a sequence close to another actively transcribed
      gene (TOM1) and an alphoid satellite sequence that underlies centromeric
      heterochromatin. Nascent strand abundance assays gave no indication that the
      heterochromatin sequence serves as a replication initiation site, suggesting that
      an ORC on this site may perform functions other than replication initiation.

PMID- 12004061
TI  - Different substrate recognition motifs of human and trypanosome nucleobase
      transporters. Selective uptake of purine antimetabolites.
AB  - The therapeutic index of antimetabolites such as purine analogues is in large
      part determined by the extent to which it is selectively accumulated by the
      target cell. In the current study we have compared the transport of purine
      nucleobase analogues by the H2 transporter of bloodstream form Trypanosoma brucei
      brucei and the equilibrative nucleobase transporter of human erythrocytes. The H2
      transporter forms hydrogen bonds with hypoxanthine at positions N3, N7, N(1)H,
      and N(9)H of the purine ring, with apparent Delta G(0) of 7.7-12.6 kJ/mol. The
      transporter also appears to H-bond with the amine group of adenine. The human
      transporter forms hydrogen bonds that form to (6)NH(2) and N1 of adenine. An H
      bond is also formed with N3 and the 6-keto and amine groups of guanine but not
      with the protonated N1, thus explaining the low affinity for hypoxanthine. N7 and
      N9 do not directly interact with the human transporter in the form of H-bonds,
      and it is proposed that pi-pi stacking interactions contribute significantly to
      permeant binding. The potential for selective uptake of antimetabolites by the
      parasite transporter was demonstrated.

PMID- 12004063
TI  - Structure-function studies of two novel UDP-GlcNAc C6 dehydratases/C4 reductases.
      Variation from the SYK dogma.
AB  - Two subfamilies of UDP-GlcNAc C6 dehydratases were recently identified. FlaA1, a
      short soluble protein that exhibits a typical SYK catalytic triad, characterizes
      one of these subfamilies, and WbpM, a large membrane protein that harbors an
      altered SMK triad that was not predicted to sustain activity, represents the
      other subfamily. This study focuses on investigating the structure and function
      of these C6 dehydratases and the role of the altered triad as well as additional
      amino acid residues involved in catalysis. The significant activity retained by
      the FlaA1 Y141M triad mutant and the low activity of the WbpM M438Y mutant
      indicated that the methionine residue was involved in catalysis. A Glu(589)
      residue, which is conserved only within the large homologues, was shown to be
      essential for activity in WbpM. Introduction of this residue in FlaA1 enhanced
      the activity of the corresponding V266E mutant. Hence, this glutamate residue
      might be responsible for the retention of catalytic efficiency in the large
      homologues despite alteration of their catalytic triad. Mutations of residues
      specific for the short homologues (Asp(70), Asp(149)-Lys(150), Cys(103))
      abolished the activity of FlaA1. Among them, C103M prevented dimerization but did
      not significantly affect the secondary structure. The fact that we could identify
      subfamily-specific residues that are essential for catalysis suggested an
      independent evolution for each subfamily of C6 dehydratases. Finally, the loss of
      activity of the FlaA1 G20A mutant provided evidence that a cofactor is involved
      in catalysis, and kinetic study of the FlaA1 H86A mutant revealed that this
      conserved histidine is involved in substrate binding. None of the mutations
      investigated altered the substrate, product, and function specificity of these
      enzymes.

PMID- 12004062
TI  - Tumor necrosis factor-alpha-induced proteolytic activation of pro-matrix
      metalloproteinase-9 by human skin is controlled by down-regulating tissue
      inhibitor of metalloproteinase-1 and mediated by tissue-associated chymotrypsin
      like proteinase.
AB  - The proteolytic activation of pro-matrix metalloproteinase (MMP)-9 by conversion
      of the 92-kDa precursor into an 82-kDa active form has been observed in chronic
      wounds, tumor metastasis, and many inflammation-associated diseases, yet the
      mechanistic pathway to control this process has not been identified. In this
      report, we show that the massive expression and activation of MMP-9 in skin
      tissue from patients with chronically unhealed wounds could be reconstituted in
      vitro with cultured normal human skin by stimulation with transforming growth
      factor-beta and tumor necrosis factor (TNF)-alpha. We dissected the mechanistic
      pathway for TNF-alpha induced activation of pro-MMP-9 in human skin. We found
      that proteolytic activation of pro-MMP-9 was mediated by a tissue-associated
      chymotrypsin-like proteinase, designated here as pro-MMP-9 activator (pM9A). This
      unidentified activator specifically converted pro-MMP-9 but not pro-MMP-2,
      another member of the gelatinase family. The tissue-bound pM9A was steadily
      expressed and not regulated by TNF-alpha, which indicated that the cytokine
      mediated activation of pro-MMP-9 might be regulated at the inhibitor level.
      Indeed, the skin constantly secreted tissue inhibitor of metalloproteinase-1 at
      the basal state. TNF-alpha, but not transforming growth factor-beta, down
      regulated this inhibitor. The TNF-alpha-mediated activation of pro-MMP-9 was
      tightly associated with down-regulation of tissue inhibitor of metalloproteinase
      1 in a dose-dependent manner. To establish this linkage, we demonstrate that the
      recombinant tissue inhibitor of metalloproteinase-1 could block the activation of
      pro-MMP-9 by either the intact skin or skin fractions. Thus, these studies
      suggest a novel regulation for the proteolytic activation of MMP-9 in human
      tissue, which is mediated by tissue-bound activator and controlled by down
      regulation of a specific inhibitor.

PMID- 12004064
TI  - Reconstitution of a disulfide isomerization system.
AB  - Isomerization of disulfide bonds is vital for the proper folding of proteins that
      possess multiple disulfides. In prokaryotes, the catalytic pathway responsible
      for disulfide isomerization involves thioredoxin, thioredoxin reductase, and the
      DsbC, DsbG, and DsbD proteins. To be active as isomerases, DsbC and DsbG must be
      kept reduced. This task is performed by the cytoplasmic membrane protein DsbD.
      DsbD in turn is reduced by the cytoplasmic thioredoxin and is composed of three
      domains. The beta domain is membrane-embedded, whereas the alpha and gamma
      domains are localized to the periplasm. It had been proposed that electrons are
      transferred within DsbD by a succession of disulfide exchange reactions between
      the three domains. To test this model using biochemical methods, we purified to
      homogeneity different polypeptides corresponding to the alpha, beta, gamma, and
      betagamma domains. Using these domains, we could reconstitute a DsbD activity
      and, for the first time, reconstitute in vitro the electron transport pathway
      from NADPH and thioredoxin to DsbC and DsbG. We showed that electrons are
      transferred from thioredoxin to the beta domain then successively to the gamma
      domain, the alpha domain, and finally on to DsbC or DsbG. We also determined the
      redox potential of the gamma domain to be -241 mV, and that of the alpha domain
      was found to be -229 mV. This shows that the direction of electron flow within
      DsbD is thermodynamically driven.

PMID- 12004065
TI  - The N-terminal domain of the reticulocyte-type 15-lipoxygenase is not essential
      for enzymatic activity but contains determinants for membrane binding.
AB  - The rabbit reticulocyte-type 15-lipoxygenase is capable of oxygenating
      biomembranes and lipoproteins without the preceding action of ester lipid
      cleaving enzymes. This reaction requires an efficient membrane binding, and the N
      terminal beta-barrel domain of the enzyme has been implicated in this process. To
      obtain detailed information on the structural requirements for membrane
      oxygenation, we expressed the rabbit wild-type 15-lipoxygenase, its beta-barrel
      deletion mutant (catalytic domain), and several lipoxygenase point mutations as
      His-tagged fusion proteins in Escherichia coli and tested their membrane binding
      characteristics. We found that: (i) the beta-barrel deletion mutant was
      catalytically active and its enzymatic properties (K(M), V(max), pH optimum,
      substrate specificity) were similar to those of the wild-type enzyme; (ii) when
      compared with the wild-type lipoxygenase, the membrane binding properties of the
      N-terminal truncation mutant were impaired but not abolished, suggesting a role
      of the catalytic domain in membrane binding; and (iii) Phe-70 and Leu-71
      (constituents of the beta-barrel domain) but also Trp-181, which is located in
      the catalytic domain, were identified as sequence determinants for membrane
      binding. Mutation of these amino acids to more polar residues (F70H, L71K, W181E)
      impaired the membrane binding capacity of the recombinant enzyme. These data
      indicate that the C-terminal catalytic domain of the rabbit 15-lipoxygenase is
      enzymatically active and that the membrane binding properties of the enzyme are
      determined by a concerted action of the N-terminal beta-barrel and the C-terminal
      catalytic domain.

PMID- 12004066
TI  - The phase property of membrane phospholipids is affected by the functionality of
      signal peptides from the Escherichia coli ribose-binding protein.
AB  - We examined the effects of synthetic signal peptides from the wild-type, export
      defective mutant and its revertant species of ribose-binding protein on the phase
      properties of lipid bilayers. The lateral segregation of phosphatidylglycerol
      (PG) in the lipid bilayer was detected through quenching between NBD-PGs upon the
      reconstitution of signal peptide into the liposome made with the Escherichia coli
      inner membrane composition. The tendency of lipid segregation was highly
      dependent on the export competency of signal peptides in vivo, with a decreasing
      order of wild-type, revertant, and mutant species. The colocalizations of pyrene
      PG with BODIPY-PG were also induced by the signal peptides, confirming the phase
      separation of the acidic phospholipid. The wild-type and revertant signal
      peptides predominantly formed alpha-helical conformations with the presence of
      acidic phospholipid as determined by circular dichroism spectroscopy. In
      addition, they restricted the motion of lipid acyl chains as monitored by
      fluorescence anisotropy of DPH, suggesting a deep penetration of signal peptide
      into the lipid bilayer. However, the alpha-helical content of mutant signal
      peptide was only about half that of the wild-type or revertant peptide with a
      significantly smaller degree of penetration into the bilayer. An association of
      the defective signal peptides into the membrane was affected by salt extraction,
      whereas the functional ones were not. The aforementioned results indicate that
      the functionality of signal peptide is accomplished through its topologies in the
      membrane and also by its ability to induce lateral segregation of acidic
      phospholipid. We propose that the clustering of acidic phospholipid by the
      functional signal peptide is responsible for the formation of non-bilayer
      membrane structure, thereby promoting an efficient translocation of secretory
      proteins.

PMID- 12004067
TI  - X-ray structure of a neuronal complexin-SNARE complex from squid.
AB  - Nerve terminals release neurotransmitters from vesicles into the synaptic cleft
      upon transient increases in intracellular Ca(2+). This exocytotic process
      requires the formation of trans SNARE complexes and is regulated by accessory
      proteins including the complexins. Here we report the crystal structure of a
      squid core complexin-SNARE complex at 2.95-A resolution. A helical segment of
      complexin binds in anti-parallel fashion to the four-helix bundle of the core
      SNARE complex and interacts at its C terminus with syntaxin and synaptobrevin
      around the ionic zero layer of the SNARE complex. We propose that this structure
      is part of a multiprotein fusion machinery that regulates vesicle fusion at a
      late pre-fusion stage. Accordingly, Ca(2+) may initiate membrane fusion by acting
      directly or indirectly on complexin, thus allowing the conformational transitions
      of the trans SNARE complex that are thought to drive membrane fusion.

PMID- 12004068
TI  - The membrane-peripheral subunits of transhydrogenase from Entamoeba histolytica
      are functional only when dimerized.
AB  - Unlike their bacterial and mammalian counterparts, the NADP(H)- and NAD(H)
      binding components of proton-translocating transhydrogenase from the protozoan
      parasite Entamoeba histolytica (denoted ehdIII and ehdI, respectively) are
      tethered by a polypeptide linker. The recombinant tethered fragment, ehdIII-ehdI,
      was prepared without its membrane-spanning dII component. Dimers of ehdIII-ehdI
      catalyzed transhydrogenation, but monomers were inactive. The addition of ehdIII
      to ehdIII-ehdI monomers did not lead to an increase in the rate of
      transhydrogenation, showing that this inactivity is not the result of an
      unfavorable topology introduced by the linker. The addition of a bacterial dI to
      ehdIII-ehdI led to an increase in the rate of transhydrogenation, showing that
      the linker is flexible. A hybrid protein in which ehdIII is tethered to the
      bacterial dI (denoted ehdIII-rrdI) more readily formed active dimers. Data from
      small angle x-ray scattering by the hybrid dimers were fitted to models derived
      from the high-resolution crystal structure of the bacterial dI(2)dIII(1) complex
      (Cotton, N. P. J., White, S. A., Peake, S. J., McSweeney, S., and Jackson, J. B.
      (2001) Structure 9, 165-T176). The results show that the ehdIII-rrdI dimer is
      asymmetric; one dIII associates with dI, as in the bacterial complex, but the
      other is displaced. The results provide evidence for the alternating site,
      binding change model for proton translocation by intact transhydrogenase.

PMID- 12004069
TI  - Thioredoxin reductase is essential for the survival of Plasmodium falciparum
      erythrocytic stages.
AB  - The human malaria parasite Plasmodium falciparum poses an increasing threat to
      human health in the tropical regions of the world, and the validation and
      assessment of possible drug targets is required for the development of new
      antimalarials. It has been shown that the erythrocytic stages of the parasites,
      which are responsible for the pathology of the disease in humans, are under
      enhanced oxidative stress and are particularly vulnerable to exogenous challenges
      by reactive oxygen species. Therefore it is postulated that the disruption of the
      antioxidant and/or redox systems of the parasite is a feasible way to interfere
      with their development during erythrocytic schizogony. In order to test this
      suggestion thioredoxin reductase (TrxR), an enzyme heavily involved in
      maintenance of redox homeostasis and antioxidant defense, was knocked out in P.
      falciparum. It was impossible to generate parasites with a disrupted trxR gene
      suggesting that TrxR is essential for P. falciparum erythrocytic stages.
      Technical problems were excluded by transfecting a 3' replacement construct,
      which recombined correctly and transfectants did not show any phenotypic
      alterations. In order to prove that the trxR knockout was responsible for the
      lethal phenotype of the null mutants, a co-transfection with both the knockout
      construct and a construct containing the trxR coding region under the control of
      the calmodulin promoter was conducted. Despite the disruption of the trxR gene,
      parasites were viable. In a Southern blot analysis a complicated restriction
      pattern was obtained, but it was shown by pulse field gel electrophoresis and
      field inverse gel electrophoreses that only the trxR gene locus on chromosome 9
      was targeted by the constructs. It was found that the co-transfected constructs
      form concatemeric structures prior to integration into the trxR gene locus, which
      is further supported by plasmid rescue followed by restriction analyses of the
      plasmids. Northern and Western blot analyses proved that the co-transfectants
      highly overexpress TrxR from the introduced gene. Our results demonstrate that
      TrxR is essential for the survival of the erythrocytic stages of P. falciparum.

PMID- 12004070
TI  - Rad52 protein has a second stimulatory role in DNA strand exchange that
      complements replication protein-A function.
AB  - Rad52 protein plays a central role in double strand break repair and homologous
      recombination in Saccharomyces cerevisiae. We have identified a new mechanism by
      which Rad52 protein stimulates Rad51 protein-promoted DNA strand exchange. This
      function of Rad52 protein is revealed when subsaturating amounts (relative to the
      single-stranded DNA concentration) of replication protein-A (RPA) are used. Under
      these conditions, Rad52 protein is needed for extensive DNA strand exchange.
      Interestingly, in this new role, Rad52 protein neither acts simply as a single
      strand DNA-binding protein per se nor, in contrast to its previously identified
      stimulatory roles, does it require physical interaction with RPA because it can
      be substituted by the Escherichia coli single strand DNA-binding protein. We
      propose that Rad52 protein acts by stabilizing the Rad51 presynaptic filament.

PMID- 12004071
TI  - IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle
      adenylosuccinate synthetase.
AB  - Prokaryotes have a single form of adenylosuccinate synthetase that controls the
      committed step of AMP biosynthesis, but vertebrates have two isozymes of the
      synthetase. The basic isozyme, which predominates in muscle, participates in the
      purine nucleotide cycle, has an active site conformation different from that of
      the Escherichia coli enzyme, and exhibits significant differences in ligand
      recognition. Crystalline complexes presented here of the recombinant basic
      isozyme from mouse show the following. GTP alone binds to the active site without
      inducing a conformational change. IMP in combination with an acetate anion
      induces major conformational changes and organizes the active site for catalysis.
      IMP, in the absence of GTP, binds to the GTP pocket of the synthetase. The
      combination of GTP and IMP results in the formation of a stable complex of 6
      phosphoryl-IMP and GDP in the presence or absence of hadacidin. The response of
      the basic isozyme to GTP alone differs from that of synthetases from plants, and
      yet the conformation of the mouse basic and E. coli synthetases in their
      complexes with GDP, 6-phosphoryl-IMP, and hadacidin are nearly identical. Hence,
      reported differences in ligand recognition among synthetases probably arise from
      conformational variations observed in partially ligated enzymes.

PMID- 12004072
TI  - Polypyrimidine tract-binding proteins are cleaved by caspase-3 during apoptosis.
AB  - The polypyrimidine tract-binding protein (PTB), an RNA-binding protein, is
      required for efficient translation of some mRNAs containing internal ribosomal
      entry sites (IRESs). Here we provide evidence that the addition of apoptosis
      inducing agents to cells results in the cleavage of PTB isoforms 1, 2, and 4 by
      caspase-3. This cleavage of PTB separated the N-terminal region, containing NLS
      RRM1, from the C-terminal region, containing RRM2-3-4. Our data indicate that
      there are three noncanonical caspase-3 target sites in PTBs, namely Ile-Val-Pro
      Asp(7)Ile, Leu-Tyr-Thr-Asp(139)Ser, and Ala-Ala-Val-Asp(172)Ala. The C-terminal
      PTB fragments localized to the cytoplasm, as opposed to the nucleus where most
      intact PTBs are found. Moreover, these C-terminal PTB fragments inhibited
      translation of polioviral mRNA, which contains an IRES element requiring PTB for
      its activation. This suggests that translation of some IRES-containing mRNAs is
      regulated by proteolytic cleavage of PTB during apoptosis.

PMID- 12004073
TI  - Comparative genome sequencing for discovery of novel polymorphisms in Bacillus
      anthracis.
AB  - Comparison of the whole-genome sequence of Bacillus anthracis isolated from a
      victim of a recent bioterrorist anthrax attack with a reference reveals 60 new
      markers that include single nucleotide polymorphisms (SNPs), inserted or deleted
      sequences, and tandem repeats. Genome comparison detected four high-quality SNPs
      between the two sequenced B. anthracis chromosomes and seven differences among
      different preparations of the reference genome. These markers have been tested on
      a collection of anthrax isolates and were found to divide these samples into
      distinct families. These results demonstrate that genome-based analysis of
      microbial pathogens will provide a powerful new tool for investigation of
      infectious disease outbreaks.

PMID- 12004074
TI  - Storage of methane and freon by interstitial van der Waals confinement.
AB  - A known host-guest assembly, organized only by means of relatively weak
      dispersive forces, exhibits hitherto unappreciated thermal stability. The
      hexagonal close-packed arrangement of calix[4]arene contains lattice voids that
      can occlude small, highly volatile molecules. This host-guest system can be
      exploited to retain a range of freons, as well as methane, not only well above
      their normal boiling points, but also at relatively high temperatures and low
      pressures. The usually overlooked van der Waals interactions in organic crystals
      can indeed be used in a highly stable supramolecular system for gas storage.

PMID- 12004075
TI  - Genomics and microbiology. Microbial forensics--"cross-examining pathogens".

PMID- 12004076
TI  - Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in
      signaling.
AB  - The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau
      tumor suppressor (pVHL) plays a central role in the cellular response to changes
      in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is
      hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom
      structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows
      that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The
      hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is
      a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by
      buried serine and histidine residues. Although the beta sheet-like interactions
      contribute to the stability of the complex, the hydroxyproline contacts are
      central to the strict specificity characteristic of signaling.

PMID- 12004077
TI  - Somatic stem cell plasticity: to be or not to be.

PMID- 12004078
TI  - Telomeres, X-inactivation ratios, and hematopoietic stem cell transplantation in
      humans: a review.
AB  - The marrow repopulating hematopoietic stem cells (HSCs) in an auto- or allograft
      represent a small fraction of the normal complement of HSCs, yet are required to
      reconstitute hematopoiesis and sustain it for the lifetime of the recipient. Such
      a burden imposes a "replicative stress" upon hematopoietic stem/progenitor cells.
      The finding of accelerated telomere shortening in hematopoietic stem cell
      transplant (HSCT) recipients raised the specter of accelerated hematopoietic
      aging. Here, we review the HSCT telomere literature and other studies of
      surrogate markers of HSC behavior conducted in human HSCT recipients. We present
      a paradigm for posttransplant hematopoietic reconstitution and speculate on the
      fate of HSCs in the human transplant setting.

PMID- 12004079
TI  - Origin and differentiation of human and murine stroma.
AB  - Stromal cells generated in long-term cultures appear to follow a vascular smooth
      muscle differentiation pathway. Such a pathway, comprising several steps
      hallmarked by the expression of cytoskeletal and extracellular matrix markers, is
      found not only for bone marrow stromal cells, but also for stromal cells
      generated from the different developmental sites of hematopoiesis (yolk sac,
      aorta-gonad-mesonephros region, fetal liver, and spleen). Factors responsible for
      this differentiation pathway and its functional significance are discussed. The
      mesenchymal founder cell might be, at least for bone marrow, a mesenchymal stem
      cell (MSC), giving rise to stromal cells, endothelial cells, adipocytes,
      osteoblasts, and chondrocytes. A feature that distinguishes the MSC lineage from
      that of the hematopoietic stem cell lineage is that differentiation pathways are
      not strictly delineated, since even apparently fully differentiated cells from a
      given lineage have the potential to convert into another lineage (phenotype
      "plasticity") and intermediate cell phenotypes are observed. A stochastic
      Repression/Induction model that would account for this plasticity is proposed.

PMID- 12004080
TI  - Cell surface antigen and molecular targeting in the treatment of hematologic
      malignancies.
AB  - Conventional cytotoxic therapy of hematologic malignancies is often associated
      with significant morbidity. This morbidity is often due to the lack of
      specificity for hematopoietic cells. Therefore, the concept of targeted therapy
      for patients with hematologic malignancies has received attention for many years.
      The goal of monoclonal antibody therapy is to target specific cell surface
      antigens on malignant hematopoietic cells, while sparing normal cells and
      tissues. Currently, monoclonal antibodies are being evaluated for their cytotoxic
      effects as well as their ability to deliver toxic agents or radiation. Rituximab,
      a chimeric anti-CD20 antibody, has shown response rates of approximately 50% with
      minimal toxicity in patients with refractory indolent lymphoma. Campath-1H (anti
      CD52) has shown encouraging results in patients previously treated for chronic
      lymphocytic leukemia, with response rates up to 33%, although with significant
      toxicity. Anti-CD33 antibodies are being used to deliver cytotoxic agents, such
      as calicheamicin to patients with acute myeloid leukemia with response rates up
      to 30%. In addition, anti-CD33 and anti-CD45 antibodies have been used to deliver
      radiation directly to leukemic cells. (131)I-labeled anti-CD45 antibodies are
      being studied in combination with conventional preparative regimens in patients
      receiving bone marrow transplantation. Lastly, the therapeutic agent STI571
      (signal transduction inhibitor 571) has demonstrated the capability of targeting
      specific molecular abnormalities seen in hematologic malignancies. STI571 targets
      the tyrosine kinase activity of the bcr-abl fusion protein seen in chronic
      myeloid leukemia. STI571 has induced complete hematologic responses in up to 98%
      of patients evaluated in clinical trials.

PMID- 12004081
TI  - Modeling stem cell development by retrospective analysis of gene expression
      profiles in single progenitor-derived colonies.
AB  - The process of development of various cell types is often based on a linear or
      deterministic paradigm. This is true, for example, for osteoblast development, a
      process that occurs through the differentiation of a subset of primitive
      fibroblast progenitors called colony-forming unit-osteoblasts (CFU-Os). CFU-O
      differentiation has been subdivided into three stages: proliferation,
      extracellular matrix development and maturation, and mineralization, with
      characteristic changes in gene expression at each stage. Few analyses have asked
      whether CFU-O differentiation, or indeed stem cell differentiation in general,
      may follow more complex and nondeterministic paths, a possibility that may
      underlie the substantial number of discrepancies in published reports of
      progenitor cell developmental sequences. We analyzed 99 single colonies of
      osteoblast stem/primitive progenitor cells cultured under identical conditions.
      The colonies were analyzed by global amplification poly(A) polymerase chain
      reaction to determine which of nine genes had been expressed. We used the
      expression profiles to develop a statistically rigorous map of the cell fate
      decisions that occur during osteoprogenitor differentiation and show that
      different developmental routes can be taken to achieve the same end point
      phenotype. These routes appear to involve both developmental "dead ends" (leading
      to the expression of genes not correlated with osteoblast-associated genes or the
      mature osteoblast phenotype) and developmental flexibility (the existence of
      multiple gene expression routes to the same developmental end point). Our results
      provide new insight into the biology of primitive progenitor cell differentiation
      and introduce a powerful new quantitative method for stem cell lineage analysis
      that should be applicable to a wide variety of stem cell systems.

PMID- 12004082
TI  - A new assay method for late CFU-S formation and long-term reconstituting activity
      using a small number of pluripotent hemopoietic stem cells.
AB  - We have previously reported that Lin-/CD71-/MHC class Ihigh/c-kit<low bone marrow
      cells (c-kit<low cells) are pluripotent hemopoietic stem cells (P-HSCs), since
      they have the capacity to self-renew for at least 2 years in mice and
      differentiate into all hemopoietic lineage cells over the long term when serial
      bone marrow transplantation is carried out using 500 c-kit<low cells. In
      addition, we have found that the c-kit<low cells do not form colony-forming units
      spleen (CFU-S) on days 8 to 14 but form late CFU-S (after 16 days). In the
      present study, to confirm that c-kit<low cells are truly P-HSCs, we examine
      whether a few (< or = 50) c-kit<low cells can form late CFU-S and reconstitute
      lethally irradiated recipients. We have established a new method to rescue
      lethally irradiated mice by transplantation of a few cells so that they survive
      for more than 16 days: 0.2 ml of 20 Gy-irradiated peripheral blood (PB) was
      injected into the recipients every 3 days. All the mice that had been
      transplanted with 25 or 50 c-kit<low cells alone died within 12 days, and no CFU
      S were detected in their spleens. However, when 25 or 50 c-kit<low cells were
      injected and 0.2 ml of 20 Gy-irradiated PB was injected every 3 days, the
      recipients survived, and a small number of CFU-S were detected after 16 days.
      About 40% of the recipients injected with 50 c-kit<low cells and about 15% of
      those injected with 25 c-kit<low cells survived for more than 6 months. Moreover,
      donor-derived multilineage cells were detected in all the hematolymphoid organs
      of the recipient mice. This new assay method using a small number of cells would
      be of great advantage for clarifying which cells are truly P-HSCs.

PMID- 12004083
TI  - Isolation and characterization of size-sieved stem cells from human bone marrow.
AB  - Bone marrow mesenchymal stem cells (MSCs) have the capacity for renewal and the
      potential to differentiate into multiple lineages of mesenchymal tissues. In the
      laboratory, MSCs have the tendency to adhere to culture dish plastic and are
      characterized by fibroblastic morphology, but possess no specific markers to
      select them. To isolate and purify MSCs from bone marrow, we use a culture device
      a plastic culture dish comprising a plate with 3-microm pores-to sieve out a
      homogeneous population of cells (termed size-sieved [SS] cells) from bone marrow
      aspirates. SS cells that adhered to the upper porous plate surface were a
      relatively homogeneous population as indicated by morphology and other criteria,
      such as surface markers. They had the capacity for self-renewal and the
      multilineage potential to form bone, fat, and cartilage, and satisfy the
      characteristics of MSCs. In addition, if all the cells from each passage had been
      plated and cultured in our defined conditions, over 10(14) SS cells would have
      been obtained from each 10-ml aspirate in 15 additional weeks of culture. This
      technically simple method leads to an efficient isolation and purification of
      cells with the characteristics of MSCs.

PMID- 12004084
TI  - Immature leukemic CD34+CXCR4+ cells from CML patients have lower integrin
      dependent migration and adhesion in response to the chemokine SDF-1.
AB  - Chronic myelogenous leukemia (CML), a malignant myeloproliferative disorder
      originating from a pluripotent stem cell expressing the bcr-abl oncogene, is
      characterized by abnormal release of the expanded, malignant stem cell clone from
      the bone marrow (BM) into the circulation. Moreover, immature CD34+ CML cells
      have lower adhesion to stromal cells and fibronectin as well as lower engraftment
      potential in severe combined immunedeficient (SCID) and nonobese diabetic
      (NOD)/SCID mice than normal CD34+ cells. We report in this study that leukemic
      Philadelphia chromosome-positive (Ph+)CD34+ cells from newly diagnosed CML
      patients that express the chemokine receptor CXCR4 migrate in response to stromal
      derived factor-1 (SDF-1). However, normal Ph-CD34+CXCR4+ cells derived from the
      same patient have significantly higher migration levels toward SDF-1. In contrast
      to their transwell migration potential, the SDF-1-mediated integrin-dependent
      polarization and migration of the Ph+CD34+CXCR4+ cells through extracellular
      matrix-like gels were significantly lower than for normal cells. Concomitantly,
      binding of these cells to vascular cell adhesion molecule-1 or fibronectin, in
      the presence of SDF-1, was also substantially lower. These findings suggest a
      major role for SDF-1-mediated, integrin-dependent BM retention of Ph+CD34+ cells.

PMID- 12004085
TI  - The molecular perspective: tamoxifen and the estrogen receptor.

PMID- 12004086
TI  - Angiotensin II that reduces the colony-forming ability of hematopoietic
      progenitors in serum free medium has an inverse effect in serum-supplemented
      medium.

PMID- 12004087
TI  - Islands, equilibria, and speciation.

PMID- 12004088
TI  - Science in the U.S. government: interim report.

PMID- 12004089
TI  - Antiterrorism. USDA closes lab doors to foreign scientists.

PMID- 12004090
TI  - U.S. appointment. Zerhouni confirmed as NIH director.

PMID- 12004091
TI  - U.S. cloning debate. Hatch signs on to pro-research bill.

PMID- 12004092
TI  - Evolutionary biology. Timing is everything for Wolbachia hosts.

PMID- 12004093
TI  - Fisheries research. No more surprises from evanescent squid.

PMID- 12004094
TI  - Microbiology. New method for culturing bacteria.

PMID- 12004095
TI  - Scientific community. U.S. science academy elects new members.

PMID- 12004096
TI  - Anthrax sequence. Useful data but no smoking gun.

PMID- 12004097
TI  - Arctic research. A man and his dog, adrift but equipped.

PMID- 12004098
TI  - Genome sequencing. Public group completes draft of the mouse.

PMID- 12004099
TI  - Environmental policy. EPA gives science a bigger voice.

PMID- 12004100
TI  - Planetary science. Safety versus science on next trips to Mars.

PMID- 12004101
TI  - Physics. The ultimate bright idea.

PMID- 12004102
TI  - Evolution of developmental diversity. Evo-devo devotees eye ocular origins and
      more.

PMID- 12004103
TI  - Virology. Monkey virus link to cancer grows stronger.

PMID- 12004104
TI  - Demography. Broken limits to life expectancy.

PMID- 12004105
TI  - Transcription. Chromatin control--a place for E2F and Myc to meet.

PMID- 12004106
TI  - Ecology. From Elton to mathematics and back again.

PMID- 12004107
TI  - Asteroids. Traces of an unusual impact.

PMID- 12004109
TI  - Radio galaxies. Bubbles, flows, and fields.

PMID- 12004108
TI  - Structural biology. Not just another ABC transporter.

PMID- 12004110
TI  - X-ray emission from comets.
AB  - The discovery of x-ray emission from comet Hyakutake was surprising given that
      comets are known to be cold. Observations by x-ray satellites such as the Rontgen
      Satellite (ROSAT) indicate that x-rays are produced by almost all comets.
      Theoretical and observational work has demonstrated that charge-exchange
      collisions of highly charged solar wind ions with cometary neutral species can
      explain this emission. X-ray observations of comets and other solar system
      objects may be used to determine the structure and dynamics of the solar wind.

PMID- 12004113
TI  - Deep life in the slow, slow lane.

PMID- 12004111
TI  - Stromal effects on mammary gland development and breast cancer.
AB  - Breast cancer manifests itself in the mammary epithelium, yet there is a growing
      recognition that mammary stromal cells also play an important role in
      tumorigenesis. During its developmental cycle, the mammary gland displays many of
      the properties associated with breast cancer, and many of the stromal factors
      necessary for mammary development also promote or protect against breast cancer.
      Here we review our present knowledge of the specific factors and cell types that
      contribute to epithelial-stromal crosstalk during mammary development. To find
      cures for diseases like breast cancer that rely on epithelial-stromal crosstalk,
      we must understand how these different cell types communicate with each other.

PMID- 12004114
TI  - Geobiologists: as diverse as the bugs they study.

PMID- 12004115
TI  - Global dispersal of free-living microbial eukaryote species.
AB  - The abundance of individuals in microbial species is so large that dispersal is
      rarely (if ever) restricted by geographical barriers. This "ubiquitous" dispersal
      requires an alternative view of the scale and dynamics of biodiversity at the
      microbial level, wherein global species number is relatively low and local
      species richness is always sufficient to drive ecosystem functions.

PMID- 12004116
TI  - Prokaryotic diversity--magnitude, dynamics, and controlling factors.
AB  - There are probably millions of species in the microorganismal domains Bacteria
      and Archaea (the prokaryotes), and we are only just beginning to work out the
      basic principles governing their distribution and abundance in natural
      environments. One characteristic that has become clear is that prokaryote
      diversity in aquatic environments is orders of magnitude less than in sediments
      and soils. Hypotheses and models explaining such differences are under
      development and are beginning to offer promising insights into the mechanisms
      governing prokaryote diversity and ecosystem function.

PMID- 12004117
TI  - Life and the evolution of Earth's atmosphere.
AB  - Harvesting light to produce energy and oxygen (photosynthesis) is the signature
      of all land plants. This ability was co-opted from a precocious and ancient form
      of life known as cyanobacteria. Today these bacteria, as well as microscopic
      algae, supply oxygen to the atmosphere and churn out fixed nitrogen in Earth's
      vast oceans. Microorganisms may also have played a major role in atmosphere
      evolution before the rise of oxygen. Under the more dim light of a young sun
      cooler than today's, certain groups of anaerobic bacteria may have been pumping
      out large amounts of methane, thereby keeping the early climate warm and
      inviting. The evolution of Earth's atmosphere is linked tightly to the evolution
      of its biota.

PMID- 12004118
TI  - Microbial behavior in a heterogeneous world.
AB  - Most microorganisms are motile during at least part of their life cycle, because
      they need to find optimal conditions in a patchy world. The sheer volume of
      microorganisms in the biosphere means that their motile sensory behavior also
      contributes to the global transformation and cycling of matter. How
      microorganisms move and how they orient themselves using environmental cues are
      integral to understanding the complex structure and function of microbial
      communities, but although motility in response to external stimuli was first
      described more than 120 years ago, understanding of the cellular and molecular
      mechanisms involved has only been achieved more recently.

PMID- 12004119
TI  - Geomicrobiology: how molecular-scale interactions underpin biogeochemical
      systems.
AB  - Microorganisms populate every habitable environment on Earth and, through their
      metabolic activity, affect the chemistry and physical properties of their
      surroundings. They have done this for billions of years. Over the past decade,
      genetic, biochemical, and genomic approaches have allowed us to document the
      diversity of microbial life in geologic systems without cultivation, as well as
      to begin to elucidate their function. With expansion of culture-independent
      analyses of microbial communities, it will be possible to quantify gene activity
      at the species level. Genome-enabled biogeochemical modeling may provide an
      opportunity to determine how communities function, and how they shape and are
      shaped by their environments.

PMID- 12004120
TI  - Merging genomes with geochemistry in hydrothermal ecosystems.
AB  - Thermophilic microbial inhabitants of active seafloor and continental hot springs
      populate the deepest branches of the universal phylogenetic tree, making
      hydrothermal ecosystems the most ancient continuously inhabited ecosystems on
      Earth. Geochemical consequences of hot water-rock interactions render these
      environments habitable and supply a diverse array of energy sources. Clues to the
      strategies for how life thrives in these dynamic ecosystems are beginning to be
      elucidated through a confluence of biogeochemistry, microbiology, ecology,
      molecular biology, and genomics. These efforts have the potential to reveal how
      ecosystems originate, the extent of the subsurface biosphere, and the driving
      forces of evolution.

PMID- 12004121
TI  - Sons reduced maternal longevity in preindustrial humans.

PMID- 12004122
TI  - The E. coli BtuCD structure: a framework for ABC transporter architecture and
      mechanism.
AB  - The ABC transporters are ubiquitous membrane proteins that couple adenosine
      triphosphate (ATP) hydrolysis to the translocation of diverse substrates across
      cell membranes. Clinically relevant examples are associated with cystic fibrosis
      and with multidrug resistance of pathogenic bacteria and cancer cells. Here, we
      report the crystal structure at 3.2 angstrom resolution of the Escherichia coli
      BtuCD protein, an ABC transporter mediating vitamin B12 uptake. The two ATP
      binding cassettes (BtuD) are in close contact with each other, as are the two
      membrane-spanning subunits (BtuC); this arrangement is distinct from that
      observed for the E. coli lipid flippase MsbA. The BtuC subunits provide 20
      transmembrane helices grouped around a translocation pathway that is closed to
      the cytoplasm by a gate region whereas the dimer arrangement of the BtuD subunits
      resembles the ATP-bound form of the Rad50 DNA repair enzyme. A prominent
      cytoplasmic loop of BtuC forms the contact region with the ATP-binding cassette
      and appears to represent a conserved motif among the ABC transporters.

PMID- 12004123
TI  - Scanned probe imaging of single-electron charge states in nanotube quantum dots.
AB  - An atomic force microscope was used to study single-electron motion in nanotube
      quantum dots. By applying a voltage to the microscope tip, the number of
      electrons occupying the quantum dot could be changed, causing Coulomb
      oscillations in the nanotube conductance. Spatial maps of these oscillations were
      used to locate individual dots and to study the electrostatic coupling between
      the dot and the tip. The electrostatic forces associated with single electrons
      hopping on and off the quantum dot were also measured. These forces changed the
      amplitude, frequency, and quality factor of the cantilever oscillation,
      demonstrating how single-electron motion can interact with a mechanical
      oscillator.

PMID- 12004124
TI  - Creation and manipulation of three-dimensional optically trapped structures.
AB  - An interferometric pattern between two annular laser beams is used to construct
      three-dimensional (3D) trapped structures within an optical tweezers setup. In
      addition to being fully translatable in three dimensions, the trapped structure
      can be rotated controllably and continuously by introducing a frequency
      difference between the two laser beams. These interference patterns could play an
      important role in the creation of extended 3D crystalline structures.

PMID- 12004125
TI  - Single-molecule optomechanical cycle.
AB  - Light-powered molecular machines are conjectured to be essential constituents of
      future nanoscale devices. As a model for such systems, we have synthesized a
      polymer of bistable photosensitive azobenzenes. Individual polymers were
      investigated by single-molecule force spectroscopy in combination with optical
      excitation in total internal reflection. We were able to optically lengthen and
      contract individual polymers by switching the azo groups between their trans and
      cis configurations. The polymer was found to contract against an external force
      acting along the polymer backbone, thus delivering mechanical work. As a proof of
      principle, the polymer was operated in a periodic mode, demonstrating for the
      first time optomechanical energy conversion in a single-molecule device.

PMID- 12004126
TI  - An efficient two-photon-generated photoacid applied to positive-tone 3D
      microfabrication.
AB  - A two-photon-activatable photoacid generator, based on a bis[(diarylamino)
      styryl]benzene core with covalently attached sulfonium moieties, has been
      synthesized. The photoacid generator has both a large two-photon absorption cross
      section (delta = 690 x 10(-50) centimeter(4) second per photon) and a high
      quantum yield for the photochemical generation of acid (phiH+ = 0.5). Under near
      infrared laser irradiation, the molecule produces acid after two-photon
      excitation and initiates the polymerization of epoxides at an incident intensity
      that is one to two orders of magnitude lower than that needed for conventional
      ultraviolet-sensitive initiators. This photoacid generator was used in
      conjunction with a positive-tone chemically amplified resist for the fabrication
      of a three-dimensional (3D) microchannel structure.

PMID- 12004127
TI  - A possible tektite strewn field in the Argentinian Pampa.
AB  - Impact glass associated with 11 elongate depressions in the Pampean Plain of
      Argentina, north of the city of Rio Cuarto, was suggested to be proximal ejecta
      related to a highly oblique impact event. We have identified about 400 additional
      elongate features in the area that indicate an aeolian, rather than an impact,
      origin. We have also dated fragments of glass found at the Rio Cuarto
      depressions; the age is similar to that of glass recovered 800 kilometers to the
      southeast. This material may be tektite glass from an impact event around 0.48
      million years ago, representing a new tektite strewn field.

PMID- 12004128
TI  - Discoidal impressions and trace-like fossils more than 1200 million years old.
AB  - The Stirling Range Formation of southwestern Australia contains discoidal
      impressions and trace-like fossils in tidal sandstones. The various disks have
      previously been linked to the Ediacaran biota, younger than 600 million years
      old. From this unit, we report U-Th-Pb geochronology of detrital zircon and
      monazite, as well as low-grade metamorphic monazite, constraining the
      depositional age to between 2016 +/- 6 and 1215 +/- 20 million years old.
      Although nonbiological origins for the discoidal impressions cannot be completely
      discounted, the structures resembling trace fossils clearly have a biological
      origin and suggest the presence of vermiform, mucus-producing, motile organisms.

PMID- 12004129
TI  - Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific
      protein SCP3.
AB  - Aneuploidy (trisomy or monosomy) is the leading genetic cause of pregnancy loss
      in humans and results from errors in meiotic chromosome segregation. Here, we
      show that the absence of synaptonemal complex protein 3 (SCP3) promotes
      aneuploidy in murine oocytes by inducing defective meiotic chromosome
      segregation. The abnormal oocyte karyotype is inherited by embryos, which die in
      utero at an early stage of development. In addition, embryo death in SCP3
      deficient females increases with advancing maternal age. We found that SCP3 is
      required for chiasmata formation and for the structural integrity of meiotic
      chromosomes, suggesting that altered chromosomal structure triggers
      nondisjunction. SCP3 is thus linked to inherited aneuploidy in female germ cells
      and provides a model system for studying age-dependent degeneration in oocytes.

PMID- 12004130
TI  - Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes.
AB  - In the fruit fly Drosophila, four insulin genes are coexpressed in small clusters
      of cells [insulin-producing cells (IPCs)] in the brain. Here, we show that
      ablation of these IPCs causes developmental delay, growth retardation, and
      elevated carbohydrate levels in larval hemolymph. All of the defects were
      reversed by ectopic expression of a Drosophila insulin transgene. On the basis of
      these functional data and the observation that IPCs release insulin into the
      circulatory system, we conclude that brain IPCs are the main systemic supply of
      insulin during larval growth. We propose that IPCs and pancreatic islet beta
      cells are functionally analogous and may have evolved from a common ancestral
      insulin-producing neuron. Interestingly, the phenotype of flies lacking IPCs
      includes certain features of diabetes mellitus.

PMID- 12004131
TI  - Stability in real food webs: weak links in long loops.
AB  - Increasing evidence that the strengths of interactions among populations in
      biological communities form patterns that are crucial for system stability
      requires clarification of the precise form of these patterns, how they come
      about, and why they influence stability. We show that in real food webs,
      interaction strengths are organized in trophic loops in such a way that long
      loops contain relatively many weak links. We show and explain mathematically that
      this patterning enhances stability, because it reduces maximum "loop weight" and
      thus reduces the amount of intraspecific interaction needed for matrix stability.
      The patterns are brought about by biomass pyramids, a feature common to most
      ecosystems. Incorporation of biomass pyramids in 104 food-web descriptions
      reveals that the low weight of the long loops stabilizes complex food webs. Loop
      weight analysis could be a useful tool for exploring the structure and
      organization of complex communities.

PMID- 12004132
TI  - Role of delayed nuclear envelope breakdown and mitosis in Wolbachia-induced
      cytoplasmic incompatibility.
AB  - The bacterium Wolbachia manipulates reproduction in millions of insects
      worldwide; the most common effect is cytoplasmic incompatibility (CI). We found
      that CI resulted from delayed nuclear envelope breakdown of the male pronucleus
      in Nasonia vitripennis. This caused asynchrony between the male and female
      pronuclei and, ultimately, loss of paternal chromosomes at the first mitosis.
      When Wolbachia were present in the egg, synchrony was restored, which explains
      suppression of CI in these crosses. These results suggest that Wolbachia target
      cell cycle regulatory proteins. A striking consequence of CI is that it alters
      the normal pattern of reciprocal centrosome inheritance in Nasonia.

PMID- 12004133
TI  - Isolating "uncultivable" microorganisms in pure culture in a simulated natural
      environment.
AB  - The majority (>99%) of microorganisms from the environment resist cultivation in
      the laboratory. Ribosomal RNA analysis suggests that uncultivated organisms are
      found in nearly every prokaryotic group, and several divisions have no known
      cultivable representatives. We designed a diffusion chamber that allowed the
      growth of previously uncultivated microorganisms in a simulated natural
      environment. Colonies of representative marine organisms were isolated in pure
      culture. These isolates did not grow on artificial media alone but formed
      colonies in the presence of other microorganisms. This observation may help
      explain the nature of microbial uncultivability.

PMID- 12004134
TI  - Volunteering as Red Queen mechanism for cooperation in public goods games.
AB  - The evolution of cooperation among nonrelated individuals is one of the
      fundamental problems in biology and social sciences. Reciprocal altruism fails to
      provide a solution if interactions are not repeated often enough or groups are
      too large. Punishment and reward can be very effective but require that defectors
      can be traced and identified. Here we present a simple but effective mechanism
      operating under full anonymity. Optional participation can foil exploiters and
      overcome the social dilemma. In voluntary public goods interactions, cooperators
      and defectors will coexist. We show that this result holds under very diverse
      assumptions on population structure and adaptation mechanisms, leading usually
      not to an equilibrium but to an unending cycle of adjustments (a Red Queen type
      of evolution). Thus, voluntary participation offers an escape hatch out of some
      social traps. Cooperation can subsist in sizable groups even if interactions are
      not repeated, defectors remain anonymous, players have no memory, and assortment
      is purely random.

PMID- 12004135
TI  - A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in
      G0 cells.
AB  - E2F-6 contributes to gene silencing in a manner independent of retinoblastoma
      protein family members. To better elucidate the molecular mechanism of repression
      by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a
      multimeric protein complex that contains Mga and Max, and thus the complex can
      bind not only to the E2F-binding site but also to Myc- and Brachyury-binding
      sites. Moreover, the complex contains chromatin modifiers such as a novel histone
      methyltransferase that modifies lysine 9 of histone H3, HP1gamma, and Polycomb
      group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters
      in G0 cells rather than in G1 cells. These data suggest that these chromatin
      modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent
      cells.

PMID- 12004136
TI  - Autosomal dominant mutations affecting X inactivation choice in the mouse.
AB  - X chromosome inactivation is the silencing mechanism eutherian mammals use to
      equalize the expression of X-linked genes between males and females early in
      embryonic development. In the mouse, genetic control of inactivation requires
      elements within the X inactivation center (Xic) on the X chromosome that
      influence the choice of which X chromosome is to be inactivated in individual
      cells. It has long been posited that unidentified autosomal factors are essential
      to the process. We have used chemical mutagenesis in the mouse to identify
      specific factors involved in X inactivation and report two genetically distinct
      autosomal mutations with dominant effects on X chromosome choice early in
      embryogenesis.

PMID- 12004137
TI  - [Inhaled nitric oxide in the therapy of acute hypoxemic respiratory failure of
      newborn].
AB  - AIM: To determine the efficiency of inhaled nitric oxide(INO) in term and preterm
      newborns with acute hypoxemic respiratory failure(AHRF), influence of this
      therapy on the systemic circulation and efficiency of the therapy in relation to
      the applied ventilation (conventional or oscillatory (HFOV)). METHODS: Term and
      preterm ventilated newborns with acute hypoxemic respiratory failure with
      oxygenation index(OI) >/= 15 were included. The mode of ventilation was not
      changed before initiation and was continued during INO therapy. Starting dose of
      INO was 20 parts per million (ppm) and during the last two years it was 1 Oppm.
      Heart rate, arterial blood pressure, methaemoglobin level, diuresis (in urinary
      catheterized newborns) were monitored. The efficiency of INO was determined on
      the ground of 20% decrease of 01. RESULTS: Investigations were performed in 43
      term and premature newborns. After initiation of INO there was a statistically
      significant fall of 01. Therapy was effective in 72.1 % patients. There was no
      influence of the therapy on the systemic circulation heart rate and medial artery
      pressure were statistically unchanged. In 16 catheterized newborns statistically
      essential increase of diuresis was observed. This effect was more distinct in
      patients in whom INO therapy was effective. INO therapy was more effective in
      newborns with respiratory distress syndrome, congenital infection and adult
      respiratory distress syndrome and less effective in newborns with respiratory
      distress syndrome with congenital infection and meconium aspiration syndrome.
      There were no essential differences in efficiency of INO between patients
      ventilated conventionally and oscillatory. CONCLUSIONS: INO improves oxygenation
      in term and preterm newborns with AHRF. INO does not cause depression of the
      systemic circulation. The increase of diuresis after initiation of INO seems to
      be associated with improving of oxygenation of the patients. This observation
      needs to be confirmed by subsequent investigations. The efficacy of INO therapy
      depends on the cause of hypoxemic respiratory failure. The synergistic effect of
      INO and HFOV was not confirmed.

PMID- 12004138
TI  - [Serum leptin level in prepubertal children with simple obesity. Part one].
AB  - The aim of the study was to determine the serum leptin level and anthropometric
      indices (body mass index - BMI) in a group of prepubertal children with simple
      obesity. These parameters were compared with the values characteristic for the
      group of slim children. The study showed that serum leptin levels were
      significantly higher in obese children compared with the group of slim children
      (p<0.0001). There was a positive correlation (r=0.48; p<0.05) between leptin
      levels and nutritional status indices expressed by BMI. Results of this study
      suggest that leptin level in the group of children with simple obesity does not
      have an effect on satiety, on reduction of appetite or on the increment of
      adipose tissue. The study showed also that hyperleptinemia might be an effect of
      leptin resistance.

PMID- 12004139
TI  - [Influence of hiatal hernia of the diaphragm of the intensity of gastroesophageal
      reflux in children].
AB  - The aim of the study was to evaluate how the hiatal hernia acts on the
      gastroesophageal reflux (GER). We observed 52 children (31 boys, and 21 girls)
      aged from 2 months to 12 years (mean age 14,3 months), who were diagnosed as
      having GER by clinical symptoms and 24-hr oesophageal pH monitoring. All patients
      underwent barium radiological examination. According to the absence or presence
      of hiatal hernia diagnosed by barium radiology, subjects were divided into two
      groups: I- without hernia, II-with hernia. In both groups 24-hr oesophageal pH
      monitoring was analyzed. We found that patients with sliding hiatal hernia had
      significantly higher median percent total time when oesophageal pH was below 4,
      significantly higher median total number of reflux episodes and higher median
      time of duration of oesophageal episodes. Median number of episodes greater than
      five minutes did not significantly differ in both groups. We conclude that hiatal
      hernia increases the GER.

PMID- 12004140
TI  - [The impact of iodine prophylaxis programme on thyroid gland morphology and
      function in children and adolescents from the Mazowieckie Voivodship].
AB  - The project was realised within the multicentre research programme no PBZ038-08.
      In all, 2967 children aged 11-18 years were examined, including 1712 girls and
      1255 boys. The tested children came from the Mazowieckie Voivodship. Each child
      was assessed by thyroid ultrasound examination and the level of TSH, FT4
      hormones, antithyroid antibodies ATM and ATGL in the blood serum. The level ofFT3
      hormone in blood serum was assessed in every fourth child. The aim of this work
      was to determine the influence of obligatory iodine preventive treatment
      programme on the morphological and functional status of the thyroid gland in
      children and teenagers from the Mazowieckie Voivodship. The tested children were
      divided into three groups: 525 children examined in 1997, living in an area of
      moderate iodine deficiency, 1477 children tested in 1998 after a few months of
      iodine supplementation and 965 children examined in 1999 who were well
      supplemented by iodine longer than one year. The average thyroid volume and the
      incidence of focal changes in the thyroid gland were determined by
      ultrasonography, the mean of the TSH, FT4, FT3, hormone level was defined in
      blood serum in girls and in boys examined in consecutive years. In children
      tested in 1999 a reduction of the average thyroid volume and a statistically
      significant decrease of the percentage of children with goitre and with focal
      changes in the thyroid gland were observed in comparison to children tested in
      1997. The results depended on iodine prophylaxis. A statistically significant
      lower level of FT3 hormone in blood serum was recorded in children tested in 1999
      than in 1997. The largest number of children with high levels of ATM and ATGL
      antibodies in blood serum, exceeding 100 IIJ7ml, were found in 1997 (ATM in 8.6%
      of cases, ATGL in 17.3% of cases). The high level of ATGL antibodies was observed
      more frequently in children tested in 1999 than in 1998.

PMID- 12004141
TI  - [Changes in spontaneous blast transformation of children's lymphocytes which have
      been observed in vitro in the last years].
AB  - In the Immunology Department of the Institute of Mother and Child in Warsaw we
      have used lymphocyte blastic transformation test (LETT) over 30 years to study
      lymphocyte function. During the last 10 years we have noticed progressive
      elevation of lymphocyte percentage undergoing spontaneous blast transformation
      (autotransformation) in culture of these cells. The percentage rose from mean
      value of 2.5% to 14.7% in year 2000 with statistically significant difference
      already between 1985 and 1990 (2.5% versus 9.3%). The reason for this phenomenon
      is unknown and needs more investigations.

PMID- 12004142
TI  - [Efficacy of specific immunotherapy in children with seasonal allergic rhinitis
      and conjunctivitis, sensitized to grass pollen].
AB  - The aim of this study was the evaluation of efficacy of the specific
      immunotherapy using Pollinex for 3 years before the period of pollen dust in
      children with seasonal allergic rhinitis and conjunctivitis induced by grass
      pollen. The study was carried out in a group of 40 children aged 5-18 years, from
      the Outpatient Department of Immunology at the National Research Institute of
      Mother and Child. The children demonstrated clinical symptoms of seasonal
      allergic rhinitis with conjunctivitis and had a medical history typical for this
      disease. Diagnostic procedures including skin prick tests and estimation of
      specific IgE to grass pollen by Pharmacia - CAP system, gave positive results.
      The efficacy of therapy was monitored by a clinical score with 4-0 points,
      recording symptoms relating to intensity of rhinoedema, rhinorrhea, sneezing,
      itching, oedema, conjunctival congestion, pain and lacrimation. In the study
      group, 39 children (97%) with seasonal rhinitis and conjunctivitis treated by
      specific immunotherapy (Pollinex) improved. This was confirmed by a statistically
      significant difference. The results indicate that the specific immunotherapy is
      an effective treatment of seasonal allergic rhinitis with conjunctivitis in
      children sensitized to grass pollen.

PMID- 12004143
TI  - [Relation between specific IgE antibodies to grass pollens and to wheat, rye,
      soya in children with allergic disease].
AB  - The aim of this study was to investigate the relationship between the
      hypersensitivity to grass pollens (gxl) and to wheat (f4), rye ff5) and soya (fl
      4) in children with allergic disease. Specific IgE was determined by the FEIA CAP
      System. Hypersensitivity was expressed in classes from 1 to 6. Specific IgE
      antibodies against grass (gxl) in 944 children with allergic disease, aged from 6
      months to 18 years were detected. At the same time in 532 of these children -
      specific IgE to wheat and rye and in 122 children   specific IgE to soya were
      also estimated. We detected very high correlation between the hypersensitivity to
      grass and the presence of specific IgE to wheat, rye (r=0.96, p<0.01) and soya
      (r=0.90, p<0.05).

PMID- 12004144
TI  - [Parents' perception of girls with Turner's Syndrome].
AB  - Turner's syndrome is a chronic disease determined by a chromosomal aberration.
      Representation (mental image of a child) contains knowledge, fantasies,
      expectations and imaginations of a child. The purpose of the work was to try to
      give the answer to the question: what sort of representation of a girl with
      Turner's syndrome is she to her parents? The child representation has been
      described referring to three dimensions: 1. somatic; 2. cognitive; 3. social
      affective. Ten families with Turner's syndrome girls were examined.

PMID- 12004145
TI  - [Natural coagulation inhibitors; antithrombin III, protein C, protein S in
      children with hypercoagulation due to nephrotic syndrome].
AB  - Activity of AT HI, protein C and protein S was evaluated in 58 children with
      nephrotic syndrome aged between 2-17 years and in 50 healthy children aged
      between 2-16 years serving as a control group. In children with nephrotic
      syndrome measurements were conducted at three different stages of disease: onset,
      improvement and remission. The aim was to assess the effect of steroid therapy on
      activity of the above inhibitors. RESULTS: At the onset of the disease, activity
      of AT III and protein S were found to be significantly decreased whereas activity
      of protein C was significantly increased as compared with the control group.
      Activity of AT III lowered at the onset of the disease, was significantly higher
      during both the improvement and the remission stage. Activity of protein C,
      increased at the onset of the nephrotic syndrome, decreased progressively and
      significantly during the improvement stage and then again increased markedly
      during the remission. Activity of protein S, lowered at the onset and during the
      improvement stage of the nephrotic syndrome, significantly rose during the
      remission, but never reached levels observed in the control group. Activity of AT
      III and protein C within 72 hours after introduction of steroids increased
      without any marked alterations in the clinical and biochemical course of the
      nephrotic syndrome. Activity of protein S was not changed. CONCLUSIONS: There are
      marked changes in AT III and protein C activity in children with nephrotic
      syndrome. It is expected that these proteins are involved in inhibition of the
      inflammatory process and of the local and systemic coagulopathy. Raised activity
      of protein C is not accompanied by increased activity of protein. This arouses
      doubts as to whether protein C-protein S complex is effective in inhibition of
      inflammation and limitation of coagulopathy. That role may be played AT III,
      which with its sufficient rise at the early stage of treatment may limit the risk
      of thromboembolic complications in children with nephrotic syndrome.

PMID- 12004146
TI  - [Haemostasis in nephrotic syndrome].
AB  - Disturbances in haemostasis and rheology in the nephrotic syndrome frequently
      lead to coagulopathy. In spite of numerous studies the pathogenesis of that
      phenomenon remains not convincingly explained. A cause of more frequent incidence
      of evident thromboembolic events in adults (about 30%) as compared with children
      (about 3%) is not clear either. The type of glomeluropathy and the presence of
      atherosclerosis seem to be essential. Present opinions concerning the role of
      individual haemostasis components and other factors effecting the raise of
      thrombotic dispositions are shown in our study. Real effect of these disturbances
      on the incidence of thromboembolic complications in the course of glomeluropathy
      evokes many controversies. Majority of them present as a microthrombosis, with
      little or no symptoms, and markedly outnumbers evident events. They can be
      diagnosed by means of invasive and costly methods. Simple to perform and cheaper
      diagnostic methods are looked for. Global tests assessing the haemostasis are
      useless in these conditions. The number of so called "intravascular haemostasis
      activation markers" is high, but none of them are objective.

PMID- 12004147
TI  - [Application of Ethyol during chemotherapy in patients with impaired kidney
      function. Description of three cases].
AB  - Nephrotoxicity is observed in 30% of patient's treated with chemotherapy
      schedules based on cisplatin analogues. Ethyol (amiphostin) was used as a
      protectant of kidney in 3 paediatric patients with neoplastic disease. Two
      patients suffered from Wilms tumour. One of them, a 5 month old boy presented
      with agenesis of the right kidney and stage II tumour in the left kidney.
      Bilateral Wilms tumour was recognised in a 6 year old girl. In both cases
      glomerular filtration was diminished. The third patient was a girl aged 5 who had
      isolated relapse of neuroblastoma in the central nervous system. Primary
      treatment caused nephrotoxic complications such as Fanconi syndrome and
      diminished glomerular filtration (66 ml/min). In these 3 cases Ethyol was used
      every lime before analogues of cisplatin were given. Tolerance and the effect of
      this protectant were good.

PMID- 12004148
TI  - [Results of combined chemotherapy and local ophtalmic therapy of children with
      intraocular retinoblastoma].
AB  - Until recently chemotherapy in retinoblastoma was used as adjuvant therapy after
      enucleation in cases with extraretinal spread of the disease (weal extension,
      orbital extension, neoplastic infiltrates of the optic nerve at resection line,
      intracranial metastasis and generalized disease). Recent experience has proved
      that use of chemotherapy for intraocular retinoblastoma before local treatment
      (so called "chemoreduction") has allowed not only to decrease the number of
      enucleations and indications for external beam irradiation or limit the extension
      of local therapy; but also to increase the chances for vision preservation and to
      decrease the risk of severe complications. Twenty children aged 0,5-96 months
      (with lesions in 29 eyes) in whom intraocular retinoblastoma was diagnosed
      between January 1996 and June 2000, were the subject of this study. Among 29
      children, in 15 (52%) stage V according to Reese-Ellsworth was established.
      Enucleation before chemotherapy was necessary in 9 cases, and in two more
      children the eye had to be removed after 1-2 courses of chemotherapy. In 11
      remaining children (with 18 involved eyes) VEC chemotherapy combined with delayed
      local therapy (cryotherapy, photocoagulation, brachytherapy) was employed. Out of
      18 treated cases enucleation could be avoided in 13 (72%), including 12 qualified
      as Reese-Ellsworth stage II or I. No eye with stage V could be saved. First-line
      chemotherapy combined with local treatment should be standard treatment for
      intraocular retinoblastoma groups I and II. More effective therapy is required
      for advanced cases particularly for Reese-Ellsworth eye group V.

PMID- 12004149
TI  - [Treatment regimen for children and adolescents with Hodgkin's disease designed
      to decrease late complications of radiotherapy].
AB  - Between 1997 to 1999 in 9 centres of the Polish Paediatlic Leukemia/Lymphoma
      Study Group, 167 children and adolescents (aged 2-19 years) with stage 1 to IV
      Hodgkin's disease (HD) were treated according to a regimen with a limited use of
      radiotherapy (RT). All patients received B-DOPA and MVPP chemotherapy. The number
      of cycles of chemotherapy was adjusted in respective risk groups. In 13 children
      with stage IA and IIA disease with favourable prognostic factors chemotherapy
      alone was used. In other patients the dose of RT applied to lymphatic regions was
      15-46,4 Gy. In case of a small tumour at presentation and good response to
      initial chemotherapy the RT dose was 15-16 Gy. In other cases doses of 25-30 Gy
      were planned. The use of higher doses, particularly exceeding 35 Gy, in eleven
      patients, was not justified. Among all the 167 patients, three oftliem (1.2%)
      with advanced disease (Stage III-1V) did not achieve first remission. The 4-year
      overall survival (OS), relapse free survival (RFS) and event free survival (EPS)
      were 99%. 93% and 90%, respectively. Relapses occurred in 8 children (first
      remission lasted for 4-29 (median = 9 months). All 13 children in whom
      chemotherapy alone was used remain in first remission. In the group of children
      who received RT in the dose of 15-16 Gy relapse occurred in one child. Our
      preliminary analysis indicates that limited use of RT in selected cases of HD in
      children and adolescents did not show worse results of treatment. However, the
      assessment of possible influence of this regimen on the decreased rate of late
      complications requires longer follow-up.

PMID- 12004150
TI  - [Extramedullary (bone) relapse 16 months after allo bmt in a 7-year-old girl
      treated for acute lymphoblastic leukaemia from the second year of life].
AB  - 7-year-old girl treated for acute lymphoblastic leukaemia since June 1995 after
      marrow relapse (June 1997) presented with painful oedema of the upper part of
      left hip and limping, 16 months after allogeneic bone marrow transplantation
      (BMT). Bone marrow examination excluded medullary relapse. Histopathological
      investigation of periosteum and bone scrapings revealed massive leukemic
      infiltration. Radiotherapy resulted in local arrest of the malignant process.
      However, bone marrow relapse was diagnosed in the child two months later with
      subsequent death after one month.

PMID- 12004151
TI  - [Renal function in children after treatment of acute lymphoblastic leukaemia
      (ALL)].
AB  - The aim of the study was to evaluate the renal function (on the basis of serum:
      cystatin C, creatinine, beta2-microglobulin(B2M) levels, creatinine and cystatin
      C clearance, and urine osmolality) in 37 children with ALL (acute lymphoblastic
      leukaemia) after completing intensive treatment (9 in course of maintenance
      therapy), depending on nephrotoxic antibiotics use (</=3 times vs > 3 times) and
      methotrexate dose (1.0 g/m2 vs 5g/m2). The control group was formed by 15 healthy
      children. RESULTS: 1) Serum cystatin C, creatinine, beta2-microglobulin levels
      creatinine and cystatin C clearance, and urine osmolality were similar in the
      analysed and control groups. 2) We did not find any differences between the
      analyzed parameters in the groups of children: a) in maintenance therapy and
      after the end of the therapy, b) received methotrexate in the dose of 5.0 g/m2 vs
      1.0 g/m2, c) not treated children and treated </= 3 times and gt; 3 times with
      nephrotoxic antibiotics. CONCLUSION: The renal function is normal after
      completion of antileukaemic therapy in spite of previous use of nephrotoxic
      drugs.

PMID- 12004152
TI  - [Use of three-dimensional conformal radiation system in radiotherapy of solid
      tumours in children].
AB  - Three - dimensional treatment planning system using CT is the most modern tool in
      the radiotherapy of children. It is most useful in treatment of solid tumours
      when the neoplasm is very close to the vital organs. In our work we have
      presented three cases of small children in whom owing to conformal radiotherapy
      it was possible to give the treatment dose to the planning target volume (PTV)
      and spare adjacent critical organs.

PMID- 12004153
TI  - [Are the cytostatic drugs and their metabolites, excreted by patients during
      chemotherapy, hazardous for the family environment?].
AB  - In recent years the problem concerning adverse effects of excreted drugs and
      their active metabolites on other people and the environment has been found to be
      an important aspect of clinical pharmacology and environmental health. It is
      commonly known that antineoplastic drugs are hazardous to medical personnel who
      handle them, but cytostatics administered during ambulatory care are always
      transferred via the patient's organism to his home and hypothetically generate
      potential risk to other family members. The patient s home is a sub-set of the
      family environment where genetically determined predisposition to neoplastic
      disease could additionally appear. This could intensify the effect of exogenous
      factors responsible for carcinogenesis (e.g. cytostatics), and increase late
      consequences (e.g. mutations). To assess the risk the authors elaborated an
      algorithm for hazard identification and assessment of consequences of the hazard.
      Preliminary results indicated passage a/significant amounts of excreted
      cytostatics and their metabolites to the natural, hospital and also family
      environment. After excretion, mutagenic properties of these drugs were still
      observed. Chemical inactivation of the excreta of patients on chemotherapy
      completely eliminates or strongly reduces their mutagenicity. At the present time
      it is difficult to assess the total risk level of cytostalic drugs and their
      metabolites excreted by patients on chemotherapy, for their home environment.
      Risk identification based on dose-response and exposure assessment, will allow to
      determine the health, social and economic hazards and to establish standards of
      procedures with regard to the risk factor.

PMID- 12004154
TI  - [Diagnostic procedure and surgical treatment of lipoblastoma in children. Own
      experience].
AB  - Three cases of surgical treatment of the right supraclavicular fossa lipoblastoma
      in a 9-year-old boy, the mesentery lipoblastoma in a 13-month-old boy and
      retroperitoneal space lipoblastoma in a 6-month-old boy are presented. Deformity
      of supraclavicular fossa in the first patient, abdomen circumference enlargement
      in the second and right abdomen deformity in the third patient were the only
      symptoms. The above mentioned symptoms lasted respectively 5, 3 months and 7
      days. X-rays and sonography examinations showed the presence of solid capsuled
      mass of tabular structure each time. CT scans in patient with mesentery
      lipoblastoma revealed additionally a fat-like tissue of the tumour (CT
      examination in the third patient gave suspicion of lipopblastoma). All tumours
      were surgically removed - they had tabular structure and were capsuled. The
      diameters were respectively: 6.5 x 6x 4 cm, 20 x 16 x 9 cm and 13x16x6 cm. This
      is to emphasize that the results of preoperative examinations as far as size,
      borders and tabular character of both tumours were very accurate when compared
      with intraoperative picture. No postoperative complications were noted. The
      follow-up recheck period is 2 years in the first, 9 months in the second and I
      day in the third case. All boys are well.

PMID- 12004155
TI  - [Biomedical science in the era of complete sequence of human genome].
AB  - Human Genome Project has already produced a draft sequence of the human genome.
      The article discusses scientific and some social aspects of the Human Genome
      Project, especially its influence on practice and the future of molecular
      medicine.

PMID- 12004156
TI  - [An analysis of chromosomal telometric regions in diagnosis of genetic
      disorders].
AB  - In the past decade, telomeres have been reported to be involved in several
      important biological functions. It has made the study of these chromosome regions
      relevant to many areas of medical and biological sciences. (Variety of basic
      biological functions of telomeric regions and their essential role in chromosome
      function have made the study of these regions relevant to many areas of medical
      and biological sciences). Molecular structure, an essential role in homologue
      pairing and recombination as well as high frequency of recombination in telomeric
      regions are predisposing factors to the rearrangements in these regions.
      Telomeres are the most gene-rich regions in the genome. That is why any
      abnormality at the region may be clinically manifest. These features of telomeric
      regions have made them of particular interest for the studies of molecular basis
      and aetiology of genetic disorders. In this review article the structure and
      methods of analysis of telomeric regions as well as the incidence, mechanisms and
      clinical significance of their aberrations with special emphasis put on their
      role in the aetiology of mental retardation, are presented.

PMID- 12004157
TI  - [RSV infections in children including managed cases in premature babies].
AB  - The authors assessed RSV infection issues within the Department of Neonatology
      during the year 2000/2001. The epidemiology, pathology, pathogenesis and the
      clinical course were discussed. The treatment and prevention patterns have been
      also presented. There were 5 cases of RSV infection of premature neonates within
      the Department of Neonatology. One of the mothers was probably the source of
      infection. The course of infection was described as severe in two infants
      (diagnosed respiratory insufficiency) and moderate in two other cases
      (respiratory disorders improved with n-CPAP). The symptoms of disease have been
      mild only in one case. Prematurity, age between 2-6 months, lung, and heart
      pathology and immunodeficiency must be considered as negative prognostic factors.
      Development of vaccination against RSV infection seems to be crucial solution for
      preterm neonates.

PMID- 12004158
TI  - [Long-term evaluation of effectiveness for selected chest physiotherapy methods
      used in the treatment of cystic fibrosis].
AB  - The aim of this study was a long-term analysis of efficiency of selected chest
      physiotherapy methods used in the treatment of children with CF. We studied 80 CF
      children (39 male, 41 female), mean age ll.44yrs (range 6-18 yrs), with varying
      degree of severity. The study was carried out during 7 months. The subjects were
      assigned into four groups. Group had conventional postural drainage with clapping
      (33 patients, age x-11.12), group II- conventional postural drainage with
      clapping and vibration (16 patients, age x-11.25), group III - active cycle of
      breathing technique (18 patients, age x-10.5), group IV Flutter (13 patients, age
      x- 13.77). All patients had three physiotherapy sessions a day. We measured: FEV1
      FVC, FEV1/FVC, MEF 25-7 %, PEF, before and after the study. In the group with
      postural drainage with clapping we observed statistically significant decrease of
      all studied parameters. The use of additional vibration improved FVC and FEV1/FVC
      values but the improvement was not statistically significant. FEV1, PEF and MEF
      25 %, were significantly lower. Statistically significant increase of all studied
      parameters was observed in patients using ACBT. In the Flutter group we observed
      increase of FEV1 and FVC values. The other parameters were decreased without
      statistical significance. Analysis of variance of pulmonary function parameters
      between groups demonstrated significant differences in FEV1, PEF and MEF 50%
      between postural drainage with vibration and active cycle of breathing technique.
      Significant differences have also been shown in PEF between postural drainage
      with clapping and active cycle of breathing technique. We conclude that: 1)
      postural drainage with clapping is less effective compared with the other studied
      techniques.2) The use of additional vibration did not bring about improvement of
      drainage efficiency. Vibration increased airways resistance. 3) Flatter device
      may be less effective in peripheral airways clearance.

PMID- 12004159
TI  - [Congenital jejunoileal and colonic atresia].
AB  - Jejunoileal and colonic atresias are a common cause of neonatal intestinal
      obstruction. Authors present the aetiology, types of atresias, clinical symptoms,
      diagnostics, surgical treatment, problems of postoperative management and
      prognosis in the newborns with congenital intestinal atresia. In the years 1992
      2000, in the Department of Paediatric Surgery and in the Department of Pathology
      and Intensive Care of Newborn at the National Research Institute of Mother and
      Child in Warsaw, 539 newborns were surgically treated (congenital anomalies of
      gastrointestinal tract, genito-urinary system, central nervous system, defects of
      abdominal wall and diaphragm). In 21 patients jejunoileal or colonic atresia were
      confirmed. On the base of the course of treatment the authors analyse prognostic
      factors: prematurity, certain types of atresia, additional pathology accompanying
      intestinal defect, necessesity of re-section of the long part of the bowel or
      multiple anastomosis. Diagnostic and treatment problems in three patients with
      short bowel syndrome needed additional discussion.

PMID- 12004160
TI  - [Clinical characteristics of osteosarcomas and cell aneuploidy in children and
      adolescents -- retrospective studies].
AB  - The relationship between the clinical status skeletal involvement, frequency of
      metastases and histopathological grading of osteosarcomas 18 children and
      adolescents and abnormal DNA content (aneuploidy) was analysed. Our findings
      demonstrate a correlation between Index DNA (DI), percentage of aneuploidy
      population to histopathological grading and prognosis. No significant correlation
      was found between aneuploidy and the site of skeletal involvement.

PMID- 12004161
TI  - [Flow cytometry estimate of s phase cell cycle and prognosis of osteosarcoma in
      children and adolescents].
AB  - Flow cytometry analysis has been used to measure the S phase in paraffin embedded
      osteosarcoma tissues of 22 children and adolescents who were surgically treated.
      The aim of this study was the assessment of S phase cell cycle in relation to
      survival, localization of tumour and histopathological grading. Our findings
      demonstrate the usefulness of flow cytometry determination of S phase cell cycle
      as a prognostic factor. Higher percentage of S phase cells predict worse
      prognosis.

PMID- 12004162
TI  - How far are we from the most accurate classification system for chronic
      pancreatitis ?

PMID- 12004163
TI  - Localization and expression of CCR3 and CCR5 by interleukin-1 beta in the RIN-5AH
      insulin-producing model system: a protective mechanism involving down-regulation
      of chemokine receptors.
AB  - CONTEXT AND OBJECTIVE: The inflammatory cytokine interleukin-1beta has been
      considered to be an immune effector molecule in insulin dependent diabetes
      mellitus. As such, we examined its role on chemokine receptors which, when
      expressed in the pancreas, have also been associated with the development of type
      I autoimmune diabetes. DESIGN AND MAIN OUTCOME MEASURES: The presence of membrane
      and cytoplasmic levels of CCR3 and CCR5 expression is assessed by
      immunofluorescence in control and interleukin-1beta-treated RIN-5AH cells. The
      cytoplasmic expression is also shown by confocal microscopy as assessed by the
      brightness of the cells whereas enzyme-linked immunosorbent assay detects
      secreted CCR3 and CCR5 molecules by comparing optical density values as these
      derive from the control and the treated cells. Cell-fractionation experiments
      show the exact location of the intracellular pools of the chemokine receptors by
      using the rab7 monoclonal antibody as a guiding molecule. RESULTS: Interleukin
      1beta down-regulates constitutively expressed surface CCR3 and CCR5 levels
      implying receptor internalization for re-utilization or destruction, secretion or
      both. Cytoplasmic immunofluorescence and confocal microscopy demonstrate cellular
      retention of chemokine receptors by interleukin-1beta which may be released in
      the absence of interleukin-1beta as assessed by enzyme-linked immunosorbent
      assay. Finally, cell-fractionation shows the presence of both receptors in
      endosomes exhibiting an increasing density after interleukin-1beta treatment.
      CONCLUSIONS: Given the association of chemokine receptors with progression to
      diabetes, it appears that interleukin-1beta-induced down-regulation of CCR3 and
      CCR5 promotes a protective mechanism against cellular destruction. The major role
      of interleukin-1beta is to maintain these molecules within the endosomes. Thus,
      interleukin-1beta modulates the movement and the expression of constitutively
      expressed chemokine receptors and does not accentuate the total destructive
      effect suffered by the cells.

PMID- 12004164
TI  - A single treatment with IL-4 via retrovirally transduced lymphocytes partially
      protects against diabetes in BioBreeding (BB) rats.
AB  - CONTEXT: Type 1 diabetes mellitus is a T cell mediated autoimmune disease with no
      known methods of prevention. The BioBreeding rat is used as an animal model for
      the study of human Type 1 diabetes. In spite of a severe lymphopenia, these
      animals develop spontaneous diabetes at the age of 10-12 weeks. OBJECTIVE: To
      examine whether anti-inflammatory gene therapy could be used to prevent
      autoimmune diabetes in the BioBreeding rat. DESIGN: A retroviral DNA vector,
      MSCVneo.IL-4, carrying the DNA sequence encoding the rat interleukin-4, was
      designed to transfer interleukin-4 to BioBreeding rats. Spleen cells of
      prediabetic animals were activated and transduced in vitro with replication
      defective retroviruses expressing the MSCVneo.IL-4 vector. These lymphocytes were
      subsequently administered intraperitoneally to 3-4 week old prediabetic
      BioBreeding rats. Control animals were reconstituted with spleen cells transduced
      with MSCVneo vector. RESULTS: The neo gene marker was detectable by RT-PCR in rat
      spleen cells of up to 6 to 12 months after treatment. Fifty percent (6 out of 12)
      of the animals treated were protected from autoimmune disease development.
      CONCLUSION: Our results suggest that the BioBreeding rat can be used as a useful
      model to develop gene therapy regimens for diabetes. These studies provide
      further support for the hypothesis that interleukin-4 based gene therapy may have
      potential clinical value for preventing autoimmune diabetes in humans.

PMID- 12004166
TI  - Continuous low-level heat wrap therapy provides more efficacy than Ibuprofen and
      acetaminophen for acute low back pain.
AB  - STUDY DESIGN: A prospective, randomized, single (investigator) blind, comparative
      efficacy trial was conducted. OBJECTIVE: To compare the efficacy of continuous
      low-level heat wrap therapy (40 C, 8 hours/day) with that of ibuprofen (1200
      mg/day) and acetaminophen (4000 mg/day) in subjects with acute nonspecific low
      back pain. SUMMARY OF BACKGROUND DATA: The efficacy of topical heat methods, as
      compared with oral analgesic treatment of low back pain, has not been
      established. METHODS: Subjects (n = 371) were randomly assigned to heat wrap (n =
      113), acetaminophen (n = 113), or ibuprofen (n = 106) for efficacy evaluation, or
      to oral placebo (n = 20) or unheated back wrap (n = 19) for blinding. Outcome
      measures included pain relief, muscle stiffness, lateral trunk flexibility, and
      disability. Efficacy was measured over two treatment days and two follow-up days.
      RESULTS: Day 1 pain relief for the heat wrap (mean, 2) was higher than for
      ibuprofen (mean, 1.51; P = 0.0007) or acetaminophen (mean, 1.32; P = 0.0001).
      Extended mean pain relief (Days 3 to 4) for the heat wrap (mean, 2.61) also was
      higher than for ibuprofen (mean, 1.68; P = 0.0001) or acetaminophen (mean, 1.95;
      P = 0.0009). Lateral trunk flexibility was improved with the heat wrap (mean
      change, 4.28 cm) during treatment (P </= 0.009 vs acetaminophen [mean change,
      2.93 cm], P </= 0.001 vs ibuprofen [mean change, 2.51 cm]). The results were
      similar on Day 4. Day 1 reduction in muscle stiffness with the heat wrap (mean,
      16.3) was greater than with acetaminophen (mean, 10.5; P = 0.001). Disability was
      reduced with the heat wrap (mean, 4.9), as compared with ibuprofen (mean, 2.7; P
      = 0.01) and acetaminophen (mean, 2.9; P = 0.0007), on Day 4. None of the adverse
      events were serious. The highest rate (10.4%) was reported in the ibuprofen
      group. CONCLUSION: Continuous low-level heat wrap therapy was superior to both
      acetaminophen and ibuprofen for treating low back pain.

PMID- 12004167
TI  - Cells from different regions of the intervertebral disc: effect of culture system
      on matrix expression and cell phenotype.
AB  - STUDY DESIGN: This study examined how the culture system and region of cellular
      origin affect disc cell morphology and extracellular matrix production.
      OBJECTIVE: To determine the role of the cell populations in the different regions
      of the adult intervertebral disc in maintaining gradients in composition across
      the disc. SUMMARY OF BACKGROUND DATA: It is not known whether the steep profiles
      in composition across the intervertebral disc are maintained by distinct cell
      populations or whether differences in cell metabolism are determined by changes
      in the physical environment across the disc. Very little information exists on
      the matrix produced by cells from the mature, non-notochordal nucleus pulposus.
      METHODS: Cells were extracted from articular cartilage, nucleus pulposus, and the
      inner and outer anulus fibrosus of caudal discs from 18- to 24-month-old steers
      cultured in alginate or collagen gels or in monolayer. The effect of culture
      system and cell origin on cell morphology and matrix synthesis was measured using
      35S-sulphate labeling and indirect immunolocalization. RESULTS: Distinct
      morphologic differences between cells from different regions cultured in
      monolayer were retained through two passages. The rate of sulfate incorporation
      varied with cell type. Immediately after isolation, it was two- to threefold
      greater for nucleus cells than for cells from the disc inner anulus or articular
      cartilage. The rate was lowest for outer anulus cells. It also varied with
      culture system. For all cell types, the incorporation rate was highest in
      alginate and lowest in monolayer. Immunolocalization showed that nucleus cells
      stained strongly for all proteoglycan epitopes, whereas outer anulus cells
      stained least and in monolayer produced little proteoglycan. CONCLUSIONS: The
      disc has at least three distinct cell populations, which differ in morphology and
      in amount and type of matrix they produce. Cells from mature nucleus pulposus
      produced sulfated glycosaminoglycans at a high rate in contrast to reported
      results for notochordal nucleus cells. Alginate, although an appropriate culture
      system for inner anulus and nucleus cells, may not be a suitable medium for outer
      anulus cells.

PMID- 12004168
TI  - Pullout test with three lumbar interbody fusion cages.
AB  - STUDY DESIGN: In vitro biomechanical testing was performed on 12 cadaveric human
      lumbar spines. OBJECTIVE: To determine the initial dislocation resistance, as
      quantified by the pullout force of three different cage designs. SUMMARY OF
      BACKGROUND DATA: Interbody cage devices frequently are used as stand-alone cages
      in the surgical treatment of degenerative conditions in the lumbar spine. In
      contrast to the wide clinical acceptance of interbody fusion cages, there are
      only a few biomechanical studies of posterior pullout trials. METHODS:
      Cylindrical threaded cages (Ray TFC Surgical Dynamics), bullet-shaped cages
      (Stryker), and newly designed rectangular titanium cages with an endplate
      anchorage device (Marquardt) were used for posterior interbody implants. For each
      device, the pullout test was performed in four specimens on both sides (L3-L4).
      RESULTS: In the pullout test, the Stryker cages required a median pullout force
      of 130 N (minimum, 100 N; maximum, 220 N), as compared with the higher pullout
      force of the Marquardt cages (median, 605 N; minimum, 450 N; maximum, 680 N), and
      the Ray cages (median, 945 N; minimum, 125 N; maximum, 2230 N). CONCLUSIONS:
      Differences in pullout resistance were noted depending on the cage design. A cage
      design with threads or a hook device provides superior stability, as compared
      with ridges. The initial pullout resistance was highest for the Ray cages and
      lowest for the Stryker cages.

PMID- 12004170
TI  - A composite bone graft substitute for anterior cervical fusion: assessment of
      osseointegration by quantitative computed tomography.
AB  - STUDY DESIGN: An ongoing prospective nonrandomized trial was conducted with 146
      patients who underwent anterior cervical fusion with a bone graft substitute. The
      results for 78 patients followed up a minimum of 2 years are reported by an
      independent observer. OBJECTIVE: To investigate the clinical efficacy and
      osseointegration of the implant. SUMMARY OF BACKGROUND DATA: Most of the cervical
      cages provide an immediate load-bearing capacity, but not necessarily a solid
      fusion. The bony ingrowth can hardly be evaluated by flexion-extension plain
      radiographs, especially if a part of the implant is made of titanium. METHODS:
      The composite bone graft substitute consists of a rectangular fenestrated
      titanium cage filled with a highly porous hydroxyapatite cylinder soaked with
      bone marrow aspirated from a vertebra. Altogether, 102 implants were inserted for
      anterior cervical fusion. The bone ingrowth was measured in 50 patients by
      quantitative computed tomography of the implant and the adjacent vertebrae after
      1 week, then 6 and 12 months after surgery. The investigation was repeated in 24
      randomly selected patients 24 months after surgery. RESULTS: The surgery
      benefited 42 of 48 patients with myelopathy, 27 of 28 patients with
      radiculopathy, and both patients with anterior horn cell syndrome. No graft
      substitute-related complications were observed, and no revision surgery was
      performed. Six months after surgery, quantitative computed tomography showed up
      to a 14% increase in the hydroxyapatite mass in the core of the implant, which
      was statistically significant (P < 0.001). At 1 year, the newly formed
      hydroxyapatite mass increased to 23%, and in 2 years reached 24%. CONCLUSIONS:
      The composite implant is effective as a bone graft substitute, providing
      immediate load-bearing capacity, an osteoconductive scaffold, and osteoinductive
      potency. After surgery, the increase in hydroxyapatite radiodensity was apparent
      in plain computed tomography scans and confirmed to be significant by
      quantitative computed tomography.

PMID- 12004171
TI  - An electromyographic study of low-velocity rear-end impacts.
AB  - STUDY DESIGN: Experimental analysis was performed to determine the effects of low
      velocity rear-end impacts on phasic and magnitudinal activity of the cervical
      muscles in expected and unexpected conditions. OBJECTIVES: To determine the
      phasic response of the cervical muscles to increasing low-velocity rear-end
      impacts, and to compare the quantitative effects of awareness and unawareness of
      impending impact. SUMMARY OF BACKGROUND DATA: The literature contains little
      information on the etiology of whiplash injuries. Animal and cadaver studies have
      yielded some insight into the phenomenon. However, in vivo studies of the
      cervical muscular response and head-neck kinematics to low-velocity impacts are
      rare. METHODS: Seven healthy volunteers were subjected to rear-end impacts of
      4.9, 8.8, 10.8, and 13.7 m/s2 acceleration at two levels of expectation: expected
      and unexpected. 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/s2, the sternocleidomastoids
      generated up to 179% of their maximal voluntary contraction electromyogram,
      whereas the splenii and trapezii did not exceed 35% of their maximal voluntary
      contraction in most of the experimental conditions. Electromyographic variables
      were significantly affected by the levels of acceleration and expectation (P <
      0.001). The onset time and peak electromyogram time for the sternocleidomastoid
      progressively decreased with increasing levels of acceleration. The kinetic
      variables and the electromyographic variables regressed significantly on the
      acceleration (P < 0.01), explaining from 96% to 100% of the variability.
      CONCLUSIONS: Muscle responses were greater with higher levels of acceleration.
      Because the muscular component of the head-neck complex plays a central role in
      the abatement of higher acceleration levels, it may be a primary site of injury
      in the whiplash phenomenon.

PMID- 12004172
TI  - Cervical muscle dysfunction in chronic whiplash-associated disorder grade 2: the
      relevance of the trauma.
AB  - STUDY DESIGN: Surface electromyography measurements of the upper trapezius
      muscles were performed in patients with a chronic whiplash-associated disorder
      Grade 2 and those with nonspecific neck pain. OBJECTIVE: To determine the
      etiologic relation between acceleration-deceleration trauma and the presence of
      cervical muscle dysfunction in the chronic stage of whiplash-associated disorder.
      SUMMARY OF BACKGROUND INFORMATION: From a biopsychosocial perspective, the
      acceleration-deceleration trauma in patients with whiplash-associated disorder is
      not regarded as a cause of chronicity of neck pain, but rather as a risk factor
      triggering response systems that contribute to the maintenance of neck pain. One
      of the contributing factors is dysfunction of the cervical muscles. Considering
      the limited etiologic significance of the trauma, it is hypothesized that in
      patients with neck pain, there are no differences in muscle activation patterns
      between those with and those without a history of an acceleration-deceleration
      trauma. METHODS: Muscle activation patterns, expressed in normalized smooth
      rectified electromyography levels of the upper trapezius muscles, in patients
      with whiplash-associated disorder Grade 2 were compared with those of patients
      with nonspecific neck pain. The outcome parameters were the mean level of muscle
      activity before and after a physical exercise, the muscle reactivity in response
      to the exercise, and the time-dependent behavior of muscle activity after the
      exercise. RESULTS: There were no statistical significant differences in any of
      the outcome parameters between patients with whiplash-associated disorder Grade 2
      and those with nonspecific neck pain. There was only a tendency of higher muscle
      reactivity in patients with whiplash-associated disorder Grade 2. CONCLUSIONS: It
      appears that the cervical muscle dysfunction in patients with chronic whiplash
      associated disorder Grade 2 is not related to the specific trauma mechanism.
      Rather, cervical muscle dysfunction appears to be a general sign in diverse
      chronic neck pain syndromes.

PMID- 12004173
TI  - Diagnosis and management of a metastatic tumor in the atlantoaxial spine.
AB  - STUDY DESIGN: A retrospective review of a prospectively maintained spine database
      was conducted. OBJECTIVES: To review the experience of a large multidisciplinary
      tertiary referral oncology center in diagnosing and managing metastatic disease
      of the atlantoaxial spine in the era of magnetic resonance imaging, and to
      establish treatment parameters. SUMMARY OF BACKGROUND DATA: Published literature
      on the topic is limited, with conflicting opinions. Although external beam
      radiation therapy has proven value, some clinicians support aggressive surgical
      management. METHODS: This study included all the patients who presented over a 6
      year period to Memorial Sloan-Kettering Cancer Center with metastatic disease to
      the atlantoaxial spine. Demographics and diagnoses were obtained. Magnetic
      resonance images, computed tomography scans, and plain radiographs were reviewed.
      At presentation, patients with normal alignment or minimal subluxation were
      considered for nonoperative therapy, either external beam radiation therapy or
      chemotherapy. Surgery was reserved for patients with significant fracture
      subluxations, including atlantoaxial displacement more than 5 mm or angulation
      exceeding 11 degrees with displacement more than 3.5 mm. Additional operative
      indications were prior external beam radiation therapy administered to
      overlapping spinal ports, unknown primary pain, and persistent pain after
      nonoperative therapy. Patient outcome was evaluated for pain relief, neurologic
      outcomes, degree of spine involvement, and survival. RESULTS: Symptomatic
      metastatic tumor involving the atlantoaxial spine was diagnosed in 33 patients.
      The mean age at presentation was 57 years. Histologic diagnoses varied widely.
      All the patients presented with severe mechanical neck pain, but no patient had
      myelopathy related to epidural tumor or fracture subluxation. Of these 33
      patients, 25 patients initially were treated nonoperatively with either external
      beam radiation therapy (n = 23) or chemotherapy (n = 2), and 8 patients underwent
      initial operation. In this nonoperatively treated group, 23 of the 25 patients
      had significant pain resolution until death or last follow-up assessment. Five
      patients required subsequent operation: three for significant fracture
      subluxations and two after neoadjuvant chemotherapy. Of the fracture
      subluxations, two were present before external beam radiation therapy, and one
      was delayed from rapid tumor progression. Posterior instrumentation was performed
      in the 13 patients who underwent surgery. No patient required anterior
      decompression and stabilization. Significant pain resolution was achieved in all
      the surgically treated patients. CONCLUSIONS: External beam radiation therapy was
      used successfully to treat patients with normal alignment or minimal subluxation.
      Selected patients warrant immediate stabilization. Patients with persistent pain
      and inability to wean from a hard collar after nonoperative therapy also should
      be considered for surgery. Posterior stabilization provides pain relief and
      neurologic preservation or recovery without the need for anterior decompression.

PMID- 12004174
TI  - Anterior decompression for myelopathy resulting from thoracic ossification of the
      posterior longitudinal ligament.
AB  - STUDY DESIGN: A retrospective study was conducted to investigate the anterior
      decompression and fusion of 12 patients with thoracic ossification of the
      posterior longitudinal ligament. OBJECTIVE: To evaluate the effect of myelopathy
      management in which the thoracic ossification of the posterior longitudinal
      ligament is removed. SUMMARY AND BACKGROUND DATA: Very few reports have described
      operative treatments for thoracic ossification of the posterior longitudinal
      ligament. The condition is extremely rare, even in Japan. Consequently, operative
      procedures for myelopathy resulting this disorder have not been established.
      METHODS: This study involved 12 patients with thoracic ossification of the
      posterior longitudinal ligament. All the patients underwent direct removal of the
      ossification and spinal fusion using an anterior approach. A scapula-releasing
      technique was used in five patients who had major ossification of the posterior
      longitudinal ligament at Th4. The follow-up period ranged from 2.5 to 10 years
      (mean, 6.5 years). The clinical effect of the decompression was evaluated with a
      Japanese Orthopedic Association score for cervical myelopathy. The efficacy of
      the decompression was determined by postoperative computed tomography scan.
      RESULTS: Complete removal of the ossification was achieved in eight patients. In
      four patients, however, residual ossification was noted. The Japanese Orthopedic
      Association score before the operation ranged from 4 to 7 points (mean, 5.3 +/-
      0.4 points). It showed a change 3 months after the operation, ranging from 1 to 8
      points (mean, 6.9 +/- 0.5 points). At 1 year after the operation, it had changed
      to a range of 1 to 10 points (mean, 7.2 +/- 0.6 points). At the final
      consultation, it had changed further to a range of 1 to 10 points (mean, 6.9 +/-
      0.5 points). Patients whose ossification was not completely removed showed severe
      or minor postoperative deterioration. CONCLUSIONS: Total removal of the
      ossification might be required to manage severe myelopathy in patients with
      thoracic ossification of the posterior longitudinal ligament. Complete removal of
      the ossification gave good results in eight patients. Patients whose ossification
      of the posterior longitudinal ligament had not been completely removed, however,
      had a poor outcome.

PMID- 12004175
TI  - Calpain inhibition by cerebrospinal fluid and effects of calpain on intrathecal
      nerve tissue.
AB  - STUDY DESIGN: The effects of calpain on intrathecal nerve tissue in the rabbit
      were investigated. OBJECTIVE: To evaluate the chemonucleolytic side effect of
      calpain on nerve tissue in the event of accidental intrathecal calpain injection.
      SUMMARY OF BACKGROUND DATA: Calpain has a degradative effect on proteoglycans,
      and as previously shown, it is associated with chemonucleolytic action in the
      rabbit. However, its effect on nerve tissue in the event of accidental
      intrathecal injection is not clear. METHODS: The inhibitory activity of
      cerebrospinal fluid against calpain was measured in human cerebrospinal fluid
      using mu-calpain, and in different cerebrospinal fluid fractions separated by
      molecular filtration. The presence of the endogenous calpain inhibitor,
      calpastatin, in human cerebrospinal fluid was examined by Western blotting with
      anticalpastatin antibody. After intrathecal application of calpain in rabbits,
      the spinal cord nerve tissue was examined by light microscopy. RESULTS:
      Cerebrospinal fluid inhibited the enzyme reaction of calpain at its normal
      concentration. Immunoblotting with anticalpastatin antibody did not yield
      positive staining. After the intrathecal application of calpain, there was no
      evidence of degeneration in the nerve tissue of the spinal cord. CONCLUSIONS:
      This study suggests that in the event of accidental intrathecal injection of
      calpain for chemonucleolysis, the enzyme activity of calpain will be neutralized
      by cerebrospinal fluid, and the calpain should not cause unwanted side effects in
      chemonucleolysis.

PMID- 12004176
TI  - Observer variability in assessing lumbar spinal stenosis severity on magnetic
      resonance imaging and its relation to cross-sectional spinal canal area.
AB  - STUDY DESIGN: Magnetic resonance image grading of lumbar spinal stenosis severity
      was analyzed retrospectively using a common clinical format. OBJECTIVE: To assess
      the interobserver and intraobserver reliability of magnetic resonance image used
      to grade patients with lumbar spinal stenosis, as compared with cross-sectional
      spinal canal area. SUMMARY OF BACKGROUND DATA: Physicians currently classify the
      degree of lumbar spinal stenosis on magnetic resonance imaging as mild, moderate,
      or severe. Unfortunately, there is no consensus on criteria for these
      definitions. METHODS: The magnetic resonance image scans of 15 patients with
      lumbar stenosis were blindly rated by seven observers for the degree of central,
      lateral recess, and foraminal stenosis between L1-L2 and L5-S1. Weighted kappa
      statistics were performed to analyze the inter- and intraobserver agreement.
      Digitized spinal canal area measurements were calculated. Linear regression
      models were used to assess the reliability of the grading system in predicting
      the cross-sectional area. RESULTS: The average interobserver kappa score was
      0.26. Within different specialties, the interobserver reliability was higher
      among radiologists (0.40), followed by neurosurgeons (0.21) and orthopedic
      surgeons (0.15). The average intraobserver kappa score was 0.11, rising to 0.43
      after categories were combined (P = 0.001). The classification of central
      stenosis highly predicted spinal canal area (P < 0.001). CONCLUSIONS: The
      findings indicate only a fair level of agreement among all observers. However,
      the ability of the various readers to predict the degree of central stenosis was
      high. Further studies should evaluate a consensus-based, standardized magnetic
      resonance image classification aimed at improved agreement among observers.

PMID- 12004177
TI  - Pulsatile cerebrospinal fluid flow measurement using phase-contrast magnetic
      resonance imaging in patients with cervical myelopathy.
AB  - STUDY DESIGN: A technical report is presented. OBJECTIVE: To investigate the
      relation between the severity of myelopathy and the degree of cerebrospinal fluid
      flow disturbance by using magnetic resonance imaging to measure the velocity of
      the cerebrospinal fluid flow in patients with cervical spondylotic myelopathy.
      SUMMARY OF BACKGROUND DATA: Analyses of pulsatile cerebrospinal fluid flow
      measured by phase-contrast magnetic resonance imaging in healthy subjects and
      patients with Arnold-Chiari syndrome have been reported. Few studies have
      evaluated the change of pulsatile cerebrospinal fluid flow velocity and the
      waveform of the plotted velocity in patients with cervical spondylotic
      myelopathy. METHODS: Study 1: Pulsatile cerebrospinal fluid flow was measured at
      C7, positioned with cervical spine flexion and extension, to investigate the
      influence of cervical alignment on the pulsatile cerebrospinal fluid flow in five
      patients with cervical spondylotic myelopathy. Study 2: In 31 patients with
      cervical spondylotic myelopathy, pulsatile cerebrospinal fluid flow was measured
      at C3 and C7, with the neck set centrally. The relevance of cerebrospinal fluid
      flow disturbance and the severity of myelopathy evaluated by the Japanese
      Orthopedic Association scoring system also were studied. RESULTS: Study 1: The
      waveform of plotted pulsatile cerebrospinal fluid flow velocity showed no change
      resulting from the position of the cervical spine. Study 2: A high correlation
      between the Japanese Orthopedic Association score and the cerebrospinal fluid
      pulsatile flow amplitude at C7 was demonstrated (r = 0.75; P < 0.0001). The
      average Japanese Orthopedic Association score of 14 patients whose cerebrospinal
      fluid flow velocity waveforms were absent was significantly lower (P < 0.0001)
      than that of 17 patients whose waveforms were present. CONCLUSIONS: The
      disturbance of pulsatile cerebrospinal fluid flow demonstrated high correlation
      with the severity of myelopathy. Measurement of cerebrospinal fluid flow
      disturbance can quantify the degree of dural sac and spinal cord compression.

PMID- 12004178
TI  - Prenatal rotation of the lumbar spine and its relevance for the development of
      the zygapophyseal joints.
AB  - STUDY DESIGN: The intrauterine axial rotational characteristics of the lumbar
      spine were analyzed and quantified sonographically. OBJECTIVES: To determine
      whether axial rotational movements of the lumbar spine occur prenatally, which
      may influence the morphogenesis of the zygapophysial joints. SUMMARY OF
      BACKGROUND DATA: Previously, the development of lumbar zygapophysial sagittal
      joint orientation was linked to the increase in torque of the torso as upright
      posture and locomotion are adopted. However, the potential influence of prenatal
      axial rotational movement of the lumbar spine on the development of the
      zygapophysial joints has not been examined. METHODS: For this study, 52 healthy
      fetuses, gestation age 9 to 36 weeks, were monitored sonographically for
      rotational movements of the lumbar spine. By multiplanar reconstruction of the
      sonography images, exemplary segmental rotational values were acquired. This
      method was validated by directly measuring the manually induced rotation of the
      formalin-fixated fetus in addition to multiplanar reconstruction. RESULTS: Axial
      rotations of the lumbar spine were seen in most of the examined fetuses ages 9 to
      36 gestation weeks. Rotations are best assessable with multiplanar reconstruction
      in the second trimenon, when segmental rotation of the lower lumbar spine reaches
      a mean of 8 degrees (range, 4-10 degrees ). CONCLUSIONS: Fetal axial rotation of
      the lower lumbar spine reaches a degree that may functionally influence the
      morphologic development of the articular processes of the zygapophysial joints.
      In contrast to the prevalent hypothesis, lumbar spine development is already
      functionally influenced prenatally by axial rotation.

PMID- 12004179
TI  - Individual factors, occupational loading, and physical exercise as predictors of
      sciatic pain.
AB  - STUDY DESIGN: In this prospective study, a cohort of 2077 workers free of sciatic
      pain and another cohort of 327 workers with severe sciatic pain were followed up
      for 1 year. OBJECTIVE: To evaluate the effects of different risk factors on the
      incidence and persistence of sciatic pain. SUMMARY OF BACKGROUND DATA: Sciatic
      pain seems to differ from other types of low back pain in terms of etiology,
      occurrence, and prognosis. Yet only a few studies of sciatic pain exist. The role
      of individual characteristics, occupational loading, and participation in
      different sports has rarely been assessed in a study with a prospective design
      among a working population. METHODS: The subjects of this study, Finnish forest
      industry workers, replied to a modified version of the Nordic Questionnaire at
      the baseline of this study and after 1 year. The effects of the predictors on the
      1-year incidence and persistence of sciatic pain were studied with multivariable
      logistic regression modeling. RESULTS: Greater age, mental stress, smoking of
      long duration, and work-related twisting of the trunk increased the risk of
      incidental sciatic pain. Joggers had a lower risk for incidental sciatic pain,
      but a higher risk for persistent symptoms. Walking was positively associated with
      the risk of incidental pain. Greater age, mental stress, former smoking, jogging,
      and poor job satisfaction increased the risk for persistent severe sciatic pain.
      CONCLUSIONS: The findings from this study suggest that mental stress and smoking
      are independent risk factors for incidental sciatic pain. Overall physical
      exercise and most of the sports activities, except jogging and walking, had no
      effect on sciatic pain. Physical workload factors seemed to be more involved in
      the onset of sciatic pain, whereas psychosocial factors were related to the
      persistence of symptoms.

PMID- 12004181
TI  - Responsiveness of outcome measurements in rehabilitation of patients with
      posterior pelvic pain since pregnancy.
AB  - STUDY DESIGN: A cohort study was conducted. OBJECTIVE: To develop a test battery
      for evaluating the course of posterior pelvic pain since pregnancy. SUMMARY OF
      BACKGROUND DATA: Properly validated scales to evaluate the course of posterior
      pelvic pain since pregnancy are scarce. Moreover, the use of many tests would be
      too strenuous for the patient and has an unfavorable cost-benefit ratio. METHODS:
      The ability of 48 effect measures to detect clinically relevant changes over time
      (responsiveness) was tested in patients with posterior pelvic pain since
      pregnancy. In this test, 35 measures were evaluated in a group of 44 patients,
      and 16 measures in a group of 56 patients (three measures were evaluated in both
      groups). All the tests were performed at baseline and after 8 weeks treatment. A
      global impression of improvement (improved or not improved) scored by the patient
      was used as the standard for assessing the course of the disease. Responsiveness
      was examined by calculating the standardized response mean of the improved
      patients and by using a two-tailed Mann-Whitney nonparametric test to compare the
      patients who had improved and those who had not improved. RESULTS: Of the 48
      effect measures, 26 measures of five categories (activities of daily living,
      pain, hip muscle strength, spine mobility, and spine muscle strength) showed good
      correlation with the patient's global impression of improvement. The measures in
      the "mobility of the pelvic joints" category were insufficient for assessing
      clinical change in posterior pelvic pain since pregnancy. The measures in the
      "fatigue" and "pain provocation tests" categories correlated only moderately with
      clinical change. CONCLUSIONS: It seems possible to gain appropriate information
      about the course of posterior pelvic pain since pregnancy with a small test
      battery. The usefulness of the Quebec Back Pain Disability Scale, the hip
      adduction strength assessment, and the active straight-leg-raise test was proved
      by the current study. The value of 23 other instruments was substantiated, but
      further studies are needed to confirm their usefulness. The correlation of 22
      evaluated measures with the patient's global improvement was too weak for them to
      be recommended as measures of clinical changes over time in posterior pelvic pain
      since pregnancy. It is recommended that clinicians and investigators compile a
      small test battery by selecting the best representatives of the five measurement
      categories that have good correlation with the patient's global impression of
      improvement.

PMID- 12004182
TI  - Hemivertebra resection by a posterior approach: innovative operative technique
      and first results.
AB  - STUDY DESIGN: A retrospective study was conducted, with clinical evaluation of
      hemivertebra resection using transpedicular instrumentation by a posterior
      approach in young children. OBJECTIVE: To assess a new method of early
      intervention in congenital scoliosis by a posterior approach. SUMMARY OF
      BACKGROUND DATA: Previously described surgical procedures are fusion in situ,
      hemiepiphyseodesis and arthrodesis, "growing" instrumentations, and hemivertebra
      resections performed by a combined anterior and posterior approach. METHODS: For
      this study, 21 consecutive cases of congenital scoliosis managed by hemivertebra
      resection using a posterior approach only with transpedicular instrumentation
      were investigated retrospectively, with at least a 2-year follow-up period.
      Surgery was performed in patients who had congenital scoliosis with proven or
      expected deterioration, or pain resulting from the malformation. RESULTS: The
      mean Cobb angle of the main curve was 41 degrees before surgery, 14 degrees after
      surgery, and 15 degrees at the latest follow-up assessment. The angle of kyphosis
      was 24 degrees before surgery, but improved to 11 degrees after surgery. There
      was one infection, one pedicle fracture, and two failures of the initially used
      wire instrumentation. CONCLUSIONS: Posterior resection of hemivertebrae with
      transpedicular instrumentation is a safe and promising procedure that offers
      significant advantages for controlling congenital deformity: excellent correction
      in both the frontal and sagittal planes, short segment of fusion, high stability,
      no need for an anterior approach, and low neurologic risk. Surgery should be
      performed as early as possible to avert severe local deformities, to prevent
      secondary structural changes, and to avert extensive fusions.

PMID- 12004183
TI  - Surgical strategy for spinal metastases.

PMID- 12004184
TI  - The effect of nucleotomy on lumbar spine mechanics in compression and shear
      loading.

PMID- 12004185
TI  - Nocardia farcinica spinal osteomyelitis.
AB  - STUDY DESIGN: A case of disseminated Nocardia farcinica infection with spine
      involvement is reported. OBJECTIVE: To describe the first case of Nocardia
      farcinica spinal osteomyelitis, and to propose spine instrumentation with
      debridement and multiple antibiotics for treatment of nocardia spinal
      osteomyelitis. SUMMARY OF BACKGROUND DATA: Only 11 cases involving Nocardia
      asteroides spinal osteomyelitis have been reported over the past 40 years. These
      case reports describe various presentations and treatments of nocardia spinal
      osteomyelitis. METHODS: A 54-year-old nonambulant, paraparetic man was admitted
      to the authors' hospital with acutely increased low back pain, fever, and signs
      of dementia. A disseminated Nocardia farcinica infection including spinal
      osteomyelitis at T11, T12, L1, L2, and L4; epidural abscess T10-L4, L5-S1
      discitis, empyemas, cerebral abscess, and bilateral psoas abscess was noted.
      RESULTS: Antibiotic therapy, multiple debridements, and posterior instrumentation
      were performed to palliate the Nocardia farcinica infection. At a recent 3-year
      follow-up assessment, the patient was independent and ambulant. He had been off
      antibiotics for 5 months. CONCLUSIONS: Previous case reports of nocardia spinal
      osteomyelitis describe treatment with antibiotics, debridements, and arthrodesis
      with autologous bone graft. Prolonged recumbency ensued. In the reported case, a
      combination of antibiotics, debridements, arthrodesis, and posterior
      instrumentation for immediate stabilization of the spine resulted in a favorable
      outcome at 3 years.

PMID- 12004186
TI  - The benefit of neurogenic mixed evoked potentials for intraoperative spinal cord
      monitoring during correction of severe scoliosis: a case study.
AB  - STUDY DESIGN: A case report is presented. OBJECTIVE: To present a case in which
      surgical correction of a severe scoliotic curve caused unilateral loss of
      neurogenic mixed evoked potential data despite unchanged somatosensory data.
      SUMMARY OF BACKGROUND DATA: Surgical correction of large scoliotic curves
      presents a risk to the function of the spinal cord. Multimodality intraoperative
      neurophysiologic monitoring of the spinal cord is recommended during such
      procedures. METHODS: A 13-year-old girl with severe double major scoliosis
      underwent a staged operative procedure for correction of her spine deformity.
      Intraoperative neurophysiologic monitoring using somatosensory-evoked potentials
      and neurogenic mixed evoked potentials was performed for each stage. RESULTS:
      During the final stage (a T4-L5 posterior instrumentation and fusion) left
      neurogenic mixed evoked potential data were lost approximately 45 minutes after
      placement of the left-side, correcting rod. The surgeon was warned of the data
      change. Set bolts were loosened at all fixation points, and the data quickly
      returned to within normal limits of baseline. Somatosensory data never approached
      warning criteria at any point during surgery. The patient awakened with no
      neurologic deficit. CONCLUSIONS: Neurophysiologic monitoring using both
      somatosensory-evoked potentials and neurogenic mixed evoked potentials is
      recommended when surgery is performed to correct spine deformity. The Stagnara
      wake-up test, somatosensory-evoked potentials, and neurogenic mixed evoked
      potentials are important components of spinal cord monitoring during surgery, and
      should be used together for optimal protection of neurologic function.

PMID- 12004188
TI  - Retro-odontoid pseudotumor in diffuse idiopathic skeletal hyperostosis.
AB  - STUDY DESIGN: A rare case of retro-odontoid pseudotumor combined with diffuse
      idiopathic skeletal hyperostosis is presented. OBJECTIVE: To discuss the
      pathomechanism of retro-odontoid pseudotumor in diffuse idiopathic skeletal
      hyperostosis. SUMMARY OF BACKGROUND DATA: Reports describing craniovertebral
      manifestations of diffuse idiopathic skeletal hyperostosis are quite rare. Only
      two cases of an atlantoaxial subluxation and one case of an odontoid fracture
      have been reported. Myelopathy resulting from retro-odontoid pseudotumor combined
      with diffuse idiopathic skeletal hyperostosis has not been reported previously.
      METHODS: A 74-year-old man presented with spastic tetraparesis caused by a retro
      odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis.
      Transoral removal of the extradural mass combined with a dorsal atlantoaxial
      fusion was performed using a titanium frame with sublaminar cable wiring.
      RESULTS: Yellowish amorphous material extruded from between the odontoid process
      and the arch of C1 when the anterior capsule had been incised. The retro-odontoid
      mass was very firmly attached to the hypertrophied ligaments. The mass therefore
      had to be sharply dissected away to expose the dura. The histologic appearance of
      the mass consisted of poorly cell-degenerated ligament, fibrocartilage, and
      fibrin. There was a focal proliferation of small vessels, but no significant
      inflammatory component and no evidence of neoplasia. The ligaments appeared
      fibrillated, disintegrated, and fragmented. After surgery, the patient's
      neurologic function improved. CONCLUSIONS: This is the first reported case of a
      retro-odontoid pseudotumor combined with diffuse idiopathic skeletal
      hyperostosis. The secondary transfer of mechanical stress to the atlantoaxial
      segment was presented as a pathomechanism underlying the formation of this retro
      odontoid pseudotumor.

PMID- 12004189
TI  - Primary non-Hodgkin's lymphoma in multiple vertebrae presenting as a lumbar
      radicular syndrome: A case report.
AB  - STUDY DESIGN: A case report is presented. OBJECTIVE: To report and discuss a case
      of primary non-Hodgkin's lymphoma in 10 different vertebrae in the spine of a 25
      year-old woman. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, a case of
      primary bone lymphoma in several vertebrae has not been reported previously.
      METHODS: Primary bone lymphoma was diagnosed using magnetic resonance images and
      biopsy of one spine lesion. There was no other localization of the lymphoma.
      RESULTS: With chemotherapeutic treatment, the lymphoma was in remission for 16
      months. The patient then died of complications associated with acute lymphatic B
      cell leukemia. CONCLUSIONS: The incidence of primary bone lymphoma in a
      population with non-Hodgkin's lymphoma is less than 1%. A case with multiple
      localizations of lymphoma in the spine has never been reported before.

PMID- 12004190
TI  - Intramedullary injection of contrast into the cervical spinal cord during
      cervical myelography: a case report.
AB  - STUDY DESIGN: A case of iatrogenic intramedullary contrast injection during a C1
      C2 cervical myelography is reported. OBJECTIVE: To investigate the occurrence of
      iatrogenic intramedullary contrast injection during a current C1-C2 cervical
      myelography. SUMMARY OF BACKGROUND DATA: Intramedullary injection of contrast is
      a rare but serious complication of C1-C2 cervical myelography that has not been
      reported since the widespread use of magnetic resonance imaging and the NASCIS
      III study protocol. METHODS: A 39-year-old woman received an iatrogenic
      intramedullary contrast injection during a C1-C2 cervical myelography. RESULTS:
      During the procedure the patient reported right-side face, neck, and arm pain and
      parethesias. After the procedure, right arm weakness and diffuse hyperreflexia
      developed. Postmyelography imaging demonstrated intramedullary contrast and cord
      swelling. High-dose methylprednisolone was administered intravenously and the
      patient's symptoms improved. The literature and management of this rare
      complication are reviewed. CONCLUSIONS: Intramedullary cord injection is a rare
      complication of cervical myelography. The mechanism of spinal cord injury appears
      to involve a combination of physical compression from the injected liquid and
      neurotoxicity of the contrast material. Iohexol rather than metrizamide should be
      used when C1-C2 myelography is indicated in patients who are unable to undergo
      magnetic resonance imaging, or those whose pathology is inadequately demonstrated
      magnetic resonance imaging alone. In the event of contrast injection into the
      spinal cord, administration of high-dose methylprednisolone is recommended.

PMID- 12004191
TI  - Ageing and CNS remyelination.
AB  - Remyelination of demyelinated axons in the CNS is a regenerative process that,
      like many others, becomes less efficient with age. This article reviews a series
      of studies in which toxin models of demyelination have been used to characterize
      this phenomenon. The delayed rate of remyelination in older animals is associated
      with a decrease in the rate of oligodendrocyte progenitor recruitment and in the
      rate at which the recruited cells differentiate into remyelinating
      oligodendrocytes. The differences in the behaviour of oligodendrocyte lineage
      cells during remyelination in young and old animals are related to the age
      related changes that occur in the expression of growth factors that affect the
      proliferation, migration and differentiation of oligodendrocyte progenitors, and
      in the inflammatory process associated with toxin-induced demyelination. Based on
      these differences, a conceptual framework is proposed to explain the age
      associated effects on remyelination, which we have called the dysregulation
      hypothesis, and the feasibility of reversing these effects is discussed.

PMID- 12004193
TI  - Serotonin and vasopressin interact in the hypothalamus to control communicative
      behavior.
AB  - The present study investigated whether serotonin (5-HT) agonists could inhibit
      the ability of arginine-vasopressin (AVP) to induce a form of scent marking
      called flank marking by their actions in the medial preoptic-anterior
      hypothalamus (MPOA-AH). DOI, a 5-HT2A,2B,2C receptor agonist, did not inhibit AVP
      induced flank marking, but mCPP a 5-HT2A antagonist and 5-HT2B,2C agonist
      inhibited AVP-induced flank marking. In addition, the finding that 8-OH-DPAT, CGS
      12066A and SC53116 also inhibited AVP-induced flank marking suggests that 5-HT
      could also inhibit flank marking by acting through 5-HT1A, 5-HT7, 5-HT1B and/or 5
      HT4 receptor subtypes. These data support the hypothesis that 5-HT acts within
      the MPOA-AH to inhibit the ability of AVP to induce flank marking.

PMID- 12004194
TI  - Natural and manufactured objects activate the fusiform face area.
AB  - Recent fMRI studies indicate that the anterior fusiform gyrus (the fusiform face
      area, FFA) is specialized for face recognition. However, the analyses used to
      determine face selectivity have not ruled out the possibility that other object
      categories produce significant activation in the FFA, relative to baseline. In
      the current fMRI study, we use a conservative hypothesis testing approach to show
      that FFA activation is not selective for faces. Rather, the FFA response is
      almost completely explained by a graded response in which faces produce more
      activation than either manufactured or natural objects, but those categories
      produce a statistically greater response than the baseline task. These findings
      question whether the FFA can be interpreted as a specialized module for face
      recognition.

PMID- 12004195
TI  - Human hippocampal activation during transitive inference.
AB  - The medial temporal lobe contains multiple structures whose mnemonic operations
      need further delineation. One model posits the function of the hippocampus as a
      relational binder, collaborating with overlying cortices that perform encoding
      and retrieval operations. For instance, lesions of the hippocampus leave intact
      the learning of paired-associates while impairing the ability to synthesize
      information across pairs. We test this relational model with two PET studies of
      normal humans during a transitive inference task using faces that either have or
      lack relationships across the stimulus pairs. Both studies converge to support a
      relational processing model of hippocampal function.

PMID- 12004196
TI  - 5-HT1A receptor immunoreactivity in hypothalamic neurons involved in body weight
      control.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) is a regulator of feeding behavior. The
      effect of serotonin on food intake is believed to be primarily mediated via 5
      HT(1A) and 5-HT(2C) receptors, which both are expressed in hypothalamic regions
      implicated in regulation of feeding behavior. Using an antiserum to the 5-HT(1A)
      receptor, immunoreactive neurons were observed in the rat supraoptic,
      paraventricular, arcuate and ventromedial nuclei and lateral hypothalamic area. 5
      HT(1A) receptor immunoreactivity was demonstrated in neuropeptide Y-, agouti
      related peptide-, proopiomelanocortin- and cocaine- and amphetamine-regulated
      transcript-containing neurons of the arcuate nucleus. In the lateral
      hypothalamus, 5-HT(1A) receptor immunoreactivity was observed in melanin
      concentrating hormone- and orexin-containing neurons. The results suggest that
      serotonin via postsynaptic 5-HT(1A) receptors affects the release of peptides
      regulating food intake.

PMID- 12004197
TI  - Use-related gene expression patterns of rat motor cortex.
AB  - Current evidence indicates reorganization of motor cortex in association with
      motor behavior. To investigate the molecular basis for these changes rats were
      fitted with limb-restricting vests which forced the use of one forelimb for 10
      days. Using cDNA macroarrays, expression profiles of the corresponding motor
      cortices connected to the overused and immobilized limbs were analyzed. In the
      overused motor cortex up-regulations were observed exclusively, including genes
      coding for voltage-gated ion channels, trafficking and targeting proteins, and
      intracellular kinase network members (10 genes). In the contralateral immobilized
      cortex changes were restricted to down-regulation, mainly involving genes
      pertaining to DNA-binding, translation, neuronal signaling and metabolic pathways
      (9 genes). At least some of these changes are likely to represent the molecular
      substrate of use-dependent plasticity.

PMID- 12004198
TI  - Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human
      neuroblastoma cells.
AB  - We have studied the pharmacological regulation of mitochondrial activity in a
      human neuroblastoma cell line. Cyclosporin A was found to directly alter
      mitochondrial membrane potential and to decrease mitochondrial permeability as
      measured using calcein. The estrogen receptor ligands tamoxifen, nafoxidine and
      clomiphene were identified as agents which affect mitochondrial membrane
      potential in a cyclosporin A-like manner. Also when mitochondrial permeability
      was measured using calcein, tamoxifen, nafoxidine and clomiphene were effective
      in inhibiting dye loss from mitochondria. Nafoxidine and cyclosporin A inhibit
      effects of mastoparan on SH-SY5Y mitochondria. These studies indicate that
      estrogen receptor ligands appear to affect mitochondria in a cyclosporin A-like
      manner in human neuroblastoma cells.

PMID- 12004199
TI  - Nicotinic receptor expression following nicotine exposure via maternal milk.
AB  - Studies have shown nicotine is excreted into maternal milk, so that suckling
      offspring would be a target of the drug during the pre-weaning period. Since
      nicotine exposure leads to an upregulation of neuronal nicotinic receptors, this
      study examines the hypothesis that nicotine delivered via maternal milk is
      capable of altering neuronal nicotinic receptor regulation in the drug-exposed
      rat pups. The present study showed that postnatal nicotine exposure via maternal
      milk was sufficient to induce an upregulation in brain nicotinic receptors
      similar to that seen in adults that smoke. Such exposure may result in altered
      neuronal development and synaptic activity and structure, potentially leading to
      long-term behavioral, learning, and memory deficits.

PMID- 12004200
TI  - Neural processing of illusory and real contours revealed by high-density ERP
      mapping.
AB  - Event-related potential (ERP) studies have shown that responses to illusory (IC),
      as compared to no contours (NC), may differ within 200 ms following stimulus
      presentation. However, whether these responses reflect the modulation of similar,
      or the activation of distinct brain regions has never been assessed. Using ERP
      map series and source localisation analyses, we compared early responses (0-200
      ms) to IC and NC, as well as to real contours (RC). Although IC displayed higher
      field strength during the N1 component, topo-graphical analyses showed a similar
      sequence of stable field configurations in all conditions. Source localisation
      applied to the N1 map revealed bilateral activation of lateral-occipital regions.
      These results suggest that both IC and RC processing modulate a common network
      associated with filling-in processes and figure-ground segregation.

PMID- 12004201
TI  - Age-related changes in the preattentional detection of visual change.
AB  - The ability to detect changes in the environment which occur outside the focus of
      current awareness is essential if the individual is to be able to divert
      attention to biologically salient stimuli. The preattentional mechanism
      underlying the automatic detection of stimulus change in the auditory modality
      has been extensively studied by recording an event-related potential known as the
      mismatch negativity. Recently a homologous response from the visual cortex has
      also been described. Ageing has been shown to affect the efficiency of
      preattentional processing in the auditory modality, a factor which may contribute
      to cognitive changes in the elderly. It is unclear whether a similar effect
      occurs in the visual system. To investigate this issue the visual mismatch
      negativity was recorded from 12 older adults and 24 younger adults. Whereas the
      younger adults displayed a robust visual MMN, that evoked in the older adults was
      significantly reduced in amplitude. The results are indicative of age-related
      deficits in automatic visual processing.

PMID- 12004202
TI  - Septal grafts and evoked acetylcholine release in the rat hippocampus after 192
      IgG-saporin lesions.
AB  - Adult rats received intraseptal injections of 192 IgG-saporin and
      intrahippocampal grafts of septal cells. Between 6 and 10 months later, we
      assessed baseline and electrically-evoked release of tritium in hippocampal
      slices preloaded with [(3)H]choline, and the uptake of [(3)H]choline,
      [(3)H]noradrenaline and [(3)H]serotonin by hippocampal synaptosomes. The lesions
      reduced the accumulation of [(3)H]choline by approximately 40%, the evoked
      release of [(3)H]acetylcholine by approximately 90%, and the uptake of
      [(3)H]choline by synaptosomes by 90% in the dorsal hippocampus, but increased the
      relative baseline release of [(3)H]choline by +43%, and the synaptosomal uptake
      of [(3)H]noradrenaline (66%) and [(3)H]serotonin (58%) in the ventral
      hippocampus. The increased noradrenaline uptake may account for sympathetic
      ingrowth. Although the grafts of fetal septal neurons produced modest cholinergic
      effects, these effects were positive and significant.

PMID- 12004203
TI  - Co-release and interaction of two inhibitory co-transmitters in rat sacral dorsal
      commissural neurons.
AB  - Conventional whole-cell recording configuration was used to characterize the
      interaction between two inhibitory neurotransmitters, GABA and glycine, in
      synaptic bouton preparation obtained from rat sacral dorsal commissural nucleus
      (SDCN). The co-release of GABA and glycine as well as the interaction between
      their corresponding receptors was demonstrated. Furthermore, taking advantage of
      pure glycinergic terminal preparation, the possible interaction between GABA and
      glycine at synaptic level was studied. The results revealed a novel cross
      modulation between the two inhibitory cotransmitters systems. This interaction
      may contribute to sensory processing such as nociception in the mammalian deep
      dorsal horn under physiological and/or pathological conditions.

PMID- 12004204
TI  - Interaction between FK 506 and isoproterenol in the modulation of glutamate
      release from cerebrocortical nerve terminals.
AB  - We have examined the interaction between FK 506 and isoproterenol in their
      modulation of glutamate release from cerebrocortical nerve terminals
      (synaptosomes). Application of FK 506, an inhibitor of protein phosphatase 2B
      (calcineurin), resulted in a concentration-dependent potentiation of 4AP-evoked
      glutamate release. The beta-adrenergic receptor agonist isoproterenol and the
      membrane-permeable activator of protein kinase A Sp-cAMP also caused a
      significant increase in evoked glutamate release, which was occluded by FK 506
      pretreatment. By studying the voltage-dependent Ca2+ influx with fura-2, we show
      that, while FK 506 and isoproterenol alone produced a potentiation of the 4AP
      evoked increase in intracellular Ca2+, the addition of FK 506 abolished the
      isoproterenol-mediated potentiation of Ca2+ influx. Based on these results, we
      suggest that the interaction between the two substances in their potentiating
      effect occurs, at least in part, at the level of the voltage-dependent Ca2+ entry
      that affects cell excitability and glutamate release.

PMID- 12004205
TI  - Predictors of survival in recurrent rectal cancer after resection and
      intraoperative radiotherapy.
AB  - PURPOSE: This study was designed to determine predictors of survival after
      surgery and intraoperative radiotherapy for recurrent rectal cancer. METHODS:
      From a prospective database, 634 patients undergoing resection for recurrent
      rectal cancer between January 1990 and June 2000 were identified. Of these, 111
      received intraoperative radiotherapy with curative intent, and 100 were available
      for follow-up. Clinicopathologic variables from both the primary and recurrent
      operations were evaluated as predictors of disease-free and disease-specific
      survival by multivariate Cox regression and log-rank test. RESULTS: There were 54
      males and 46 females, with a median age of 57 (range, 37-83) years. With a median
      follow-up of 23.2 months, 60 patients (60 percent) recurred: 20 (33 percent)
      locally, 27 (45 percent) distantly, and 13 (22 percent) at both sites. Of all
      variables analyzed, only complete resection with microscopically negative margins
      and the absence of vascular invasion in the recurrent specimen predicted improved
      disease-free and disease-specific survival (P < 0.01 for all). Median disease
      free survival and median disease-specific survival were 31.2 and 66.1 months,
      respectively, for complete resection compared with 7.9 and 22.8 months for
      resection with microscopic or grossly positive margins (P < 0.01 for both).
      Median disease-free survival and median disease-specific survival were 6.4 and
      16.1 months, respectively, in the presence of vascular invasion in the recurrent
      specimen compared with 23.3 and 57.3 months in the absence of vascular invasion
      (P < 0.01 and P < 0.05, respectively). Complete resection and the absence of
      vascular invasion were the only predictors of improved local control as well (P <
      0.05 and P < 0.01, respectively). CONCLUSION: Resection with negative microscopic
      margins and absence of vascular invasion are independent predictors of local
      control and improved survival after resection and intraoperative radiotherapy for
      recurrent rectal cancer.

PMID- 12004206
TI  - Role of nitric oxide in the colon of patients with slow-transit constipation.
AB  - PURPOSE: The cause of dysmotility in patients with slow-transit constipation is
      unknown. Nitric oxide has recently been shown to be a neurotransmitter in the
      nonadrenergic, noncholinergic inhibitory nerves of the human gut. To clarify the
      physiologic significance of nitric oxide in the colon of patients with slow
      transit constipation, we investigated the enteric nerve responses in lesional and
      normal bowel segments derived from patients with slow-transit constipation and
      patients who underwent colon resection for colonic cancers. METHODS: Twenty-six
      preparations were taken from colonic lesions in eight patients with slow-transit
      constipation (2 men; age, 23 to 69 (mean, 44.8) years). Forty-two preparations
      were taken from the normal colons of 14 patients with colonic cancer (8 men; age,
      40 to 66 (mean, 52.4) years). A mechanographic technique was used to evaluate in
      vitro muscle responses to electric field stimulation before and after treatment
      with various autonomic nerve blockers, NG-nitro-L-arginine, and L-arginine.
      RESULTS: The colons of patients with slow-transit constipation were more strongly
      innervated by nonadrenergic, noncholinergic inhibitory nerves than were normal
      colons (P <0.05). Nitric oxide was found to act on both normal and slow-transit
      constipation colons. The colons of patients with slow-transit constipation were
      more strongly innervated by nitric oxide nerves than were normal colons (P <
      0.01). Responses to electric field stimulation were the same in each case among
      the normal colons and were also the same in each case among the slow-transit
      constipation colons. CONCLUSION: These findings suggest that an increase of
      nitric oxide mediates nonadrenergic, noncholinergic inhibitory nerves and plays
      an important role in the dysmotility observed in the colons of patients with slow
      transit constipation.

PMID- 12004207
TI  - Transanal endoscopic microsurgery excision: is anorectal function compromised?
AB  - PURPOSE: Transanal endoscopic microsurgery is a new technique that has not yet
      found its place in routine practice. The procedure results in dilation of the
      anal sphincter with a large-diameter operating sigmoidoscope, sometimes for a
      prolonged period. The purpose of the present study was to assess the effect of
      transanal endoscopic microsurgery on anorectal function. METHODS: Eighteen
      consecutive patients undergoing transanal endoscopic microsurgery excision of
      rectal tumors, of whom 13 were available for evaluation, were included.
      Continence was scored by a numeric scale before surgery and at three and six
      weeks after surgery. Anorectal physiology studies were performed preoperatively
      and six weeks postoperatively with manometry, pudendal nerve motor terminal
      latency, anal mucosal electrosensitivity, rectal balloon volume studies, and
      endoanal ultrasound. RESULTS: There was a significant reduction in mean anal
      resting pressure (104 +/- 32 cm H2O before surgery, 73 +/- 30 cm H2O after
      surgery; P = 0.0009). There was no significant change in squeeze or cough
      pressure, pudendal nerve terminal motor latency, anal mucosal electrosensitivity,
      or rectal balloon study volumes. Fall in resting pressure was significantly
      correlated with length of operating time (r2 =0.39, P = 0.047). There was no
      significant change in mean continence score after surgery. CONCLUSION: Transanal
      endoscopic microsurgery results in a reduction in internal sphincter tone. This
      did not affect continence in a short-term study.

PMID- 12004208
TI  - Advantages of laparoscopic resection for ileocecal Crohn's disease.
AB  - PURPOSE: Elective laparoscopic-assisted resection of terminal ileal Crohn's
      disease is slowly gaining acceptance as an alternative to conventional surgery,
      based on the advantages of earlier return of bowel function, reductions in length
      of stay, and smaller wounds in a population likely to require reoperation. There
      is limited documentation of the cost-effectiveness of this approach, particularly
      with the reported longer operating times. The purpose of this study was to
      compare laparoscopic and open resections for terminal ileal Crohn's disease.
      METHODS: We compared contemporaneous cohorts of patients undergoing initial
      elective laparoscopic or open resection for ileocecal Crohn's disease between
      June 1, 1999 and October 31, 2000 at a single institution. Operative approach was
      at the discretion of the surgeon. Data collected included age, gender, body mass
      index, American Society of Anesthesiologists score, indication for surgery,
      morbidity, mortality, conversion (laparoscopic-resection group only), operating
      room time, length of hospital stay, direct cost per case, 30-day readmission, and
      return to work. All data are presented as medians and interquartile ranges. Data
      analysis was performed with the Mann-Whitney U test, Fisher's exact test, and
      Student's t-test where appropriate. Significance was set at P < 0.05. RESULTS:
      There were 45 evaluable patients (laparoscopic-resection group, 21; open
      resection group, 24). One procedure was considered a conversion because of the 13
      cm incision required to exteriorize the phlegmon (conversion rate, 4.8 percent).
      The median age (laparoscopic-resection group, 31 years; open-resection group, 39
      years) and gender distributions (male/female: laparoscopic-resection group, 129;
      open-resection group, 915) were significantly different between the two groups.
      Resumption of oral intake (operating-room day vs. second postoperative day; P <
      0.05) and resumption of intestinal function (2 vs. 4 days; P < 0.05) were
      significantly faster in the laparoscopic-resection patients. The median length of
      hospital stay was significantly shorter for the laparoscopic-resection patients
      (3 (2-3) vs. 5 (4-6) days; P < 0.05). The 30-day readmission rate in the
      laparoscopic-resection group was 9.6 percent (221), whereas none of the open
      resection patients required rehospitalization. The overall complication rates
      were comparable for the laparoscopic-resection and open-resection patients (14.3
      vs. 16.7 percent; P not significant), although there was one anastomotic leak and
      one intra-abdominal abscess in the laparoscopic-resection group, requiring
      readmission and reintervention (9.6 percent; P not significant). The direct cost
      per case was significantly lower for the laparoscopic-resection group ($2,547 vs.
      $2,985; P < 0.05, Student's t-test). CONCLUSION: The laparoscopic-assisted
      approach to ileocecal Crohn's disease results in a shortened length of stay and
      seems economically advantageous to open surgery.

PMID- 12004209
TI  - On-table cecoscopy : a novel diagnostic method in acute diverticulitis of the
      right colon.
AB  - PURPOSE: Controversies abound regarding the optimal surgical management in
      noncomplicated diverticulitis of the right colon, ranging from a conservative
      approach to diverticulectomy to right hemicolectomy. One of the arguments for
      resection is to exclude carcinoma. However, there is significant morbidity
      associated with resection. We aim to introduce on-table cecoscopy as a tool to
      improve the diagnosis of acute diverticulitis of the right colon, exclude
      carcinoma, and reduce the rate of resection. METHODS: From October 1999 to June
      2000, five patients presented to our unit with suspected acute appendicitis.
      Intraoperatively, we found a colonic inflammatory mass at either the cecum or the
      ascending colon. The cecum and ascending colon were mobilized, and bowel clamps
      were applied to the ascending colon and ileum. A bronchoscope (Olympus(R) BF
      P200) was introduced through the appendix stump. To achieve a good endoscopic
      view, a limited volume of air was introduced through the working channel.
      RESULTS: After on-table cecoscopy, all the patients were diagnosed as having
      acute nonperforated diverticulitis of the right colon. They received
      appendicectomy, and the diverticulitis was managed conservatively. They were
      treated with a course of cephalosporin and metronidazole. We performed
      colonoscopy four weeks later and confirmed that none of them had carcinoma of the
      colon. CONCLUSIONS: On-table cecoscopy is a new, safe, and effective means of
      diagnosing acute diverticulitis of the right colon. We can confidently exclude
      carcinoma and reduce the amount of colonic resection in patients with
      noncomplicated diverticulitis of the right colon.

PMID- 12004210
TI  - Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a
      follow-up study.
AB  - PURPOSE: Extensive, long-standing inflammatory bowel disease is associated with
      an increased risk of developing colorectal carcinoma. Low-grade dysplasia has
      been used as a marker for malignant transformation and by some as an indication
      for prophylactic colectomy. The aim of the present study was to follow up all
      inflammatory bowel disease patients with extensive, long-standing colitis who had
      low-grade dysplasia in flat colonic mucosa. METHODS: All patients with low-grade
      dysplasia in flat mucosa found at screening or at surveillance colonoscopy with
      at least one follow-up colonoscopy or with colectomy were included. RESULTS:
      Sixty patients (40 males; mean age at diagnosis, 24 +/- 12 (range, 3-59) years)
      were found and followed up for a mean of 10 +/- 6 (range, 1-22) years. Mean time
      from onset of disease to discovery of low-grade dysplasia was 17 +/- 11 (range, 1
      55) years. Low-grade dysplasia was present in more than 1 biopsy in 37 (62
      percent) of 60 patients at the index colonoscopy. Low-grade dysplasia was again
      detected in 1.8 (1-6) subsequent colonoscopies in 44 (73 percent) of 60 patients.
      High-grade dysplasia was found in 2 of 11 patients with dysplasia-associated
      lesion or mass at follow-up. Thirteen patients were subjected to colectomy (7 for
      dysplasia, 6 for therapy failure). Dysplasia was confirmed in five of these
      patients. CONCLUSION: Although low-grade dysplasia occurred at several colonic
      levels and at repeated colonoscopies in 73 percent of the patients, no
      progression to high-grade dysplasia was found during 10 years of follow-up,
      except in 2 cases with dysplasia-associated lesion or mass. Colectomy in cases
      with single or repeated low-grade dysplasia in flat mucosa does not appear to be
      justified.

PMID- 12004211
TI  - Effect of dietary inulin supplementation on inflammation of pouch mucosa in
      patients with an ileal pouch-anal anastomosis.
AB  - PURPOSE: Inflammation is a constant finding in the ileal reservoir of patients
      with an ileal pouch-anal anastomosis and is associated with decreased fecal
      concentrations of the short chain fatty acid butyrate, increased fecal pH,
      changes in fecal flora, and increased concentrations of secondary bile acids. In
      healthy subjects, inulin, a dietary fiber, is fermented to short chain fatty
      acids and leads to a lower pH and potentially beneficial changes in fecal flora.
      The aim of the present study was to investigate the effect of enteral
      supplementation of inulin on inflammation of the ileal reservoir. METHODS: Twenty
      patients received 24 g of inulin or placebo daily during three weeks in a
      randomized, double-blind, crossover design. Stools were analyzed after each test
      period for pH, short chain fatty acids, microflora, and bile acids. Inflammation
      was assessed endoscopically, histologically, and clinically. RESULTS: Compared
      with placebo, three weeks of dietary supplementation with 24 g of inulin
      increased butyrate concentrations, lowered pH, decreased numbers of Bacteroides
      fragilis, and diminished concentrations of secondary bile acids in feces. This
      was endoscopically and histologically accompanied by a reduction of inflammation
      of the mucosa of the ileal reservoir. CONCLUSION: Enteral inulin supplementation
      leads to a decrease of inflammation-associated factors and to a reduction of
      inflammation of pouch mucosa.

PMID- 12004212
TI  - Budding as a risk factor for lymph node metastasis in pT1 or pT2 well
      differentiated colorectal adenocarcinoma.
AB  - PURPOSE: Lymph node metastasis is an important indicator of tumor stage and
      prognosis in pT1 and pT2 colorectal adenocarcinomas. Lymphovascular invasion is
      an established risk factor of lymph node metastasis, whereas budding at the
      invasive front of tumors is also reported to correlate with lymph node
      metastasis. We examined whether the coexistence of lymphovascular invasion and
      budding provides any better information than lymphovascular invasion alone in the
      prediction of lymph node metastasis of pT1 or pT2 well-differentiated colorectal
      adenocarcinomas. METHODS: Surgically resected specimens of 101 pT1 or pT2 well
      differentiated colorectal adenocarcinomas were studied. Using sections stained
      with hematoxylin-eosin, we examined lymphovascular invasion and budding according
      to Morodomi's definition. RESULTS: Lymphovascular invasion was present in 39
      lesions (38 percent), whereas budding was found in 42 lesions (41 percent).
      Budding was more frequently detected in pT2 tumors than in pT1 tumors. The
      presence of budding significantly correlated with lymphovascular invasion.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value of lymphovascular invasion alone for lymph node metastasis were 79, 76, 34,
      and 96 percent, respectively, whereas those of the combination of lymphovascular
      invasion and budding (either lymphovascular invasion or budding) were 93, 52, 24,
      and 98 percent, respectively. CONCLUSION: Because the risk of lymph node
      metastasis in pT1 or pT2 well-differentiated colorectal adenocarcinomas having
      neither lymph node metastasis nor budding is very low, budding in combination
      with lymphovascular invasion seems to be a simple and inexpensive pathologic
      marker in predicting lymph node metastasis. Therefore, the presence or absence of
      budding should be examined in the routine pathologic diagnosis of pT1 or pT2 well
      differentiated colorectal adenocarcinomas.

PMID- 12004213
TI  - Previous sphincter repair does not affect the outcome of repeat repair.
AB  - PURPOSE: As many as 60 percent of patients present with recurrent symptoms of
      fecal incontinence after anterior overlapping anal sphincter repair. The aim of
      this study was to assess the outcome of repeat overlapping anal sphincter repair.
      METHODS: All female patients with obstetric sphincter damage who underwent
      anterior overlapping sphincter repair between November 1988 and June 2000 were
      reviewed. All patients were preoperatively assessed by anorectal manometry,
      electromyography, and pudendal nerve terminal motor latency; manometry was
      repeated during follow-up. Preoperative endoanal ultrasonography was available
      only after 1990. Clinical outcome was assessed according to the Cleveland Clinic
      Florida Incontinence Score. RESULTS: One hundred fifty-one patients were
      available for analysis, 115 without previous surgery and 36 after at least one
      previous sphincter repair. The median follow-up was 13 (range, 1-64) months and
      20 (range, 2-96) months, respectively. The median incontinence score improved
      from 18 to 5 (P < 0.0001) in patients without previous repair and from 17.5 to 7
      (P < 0.0001) in patients after previous repair. In the former group, the outcome
      was good in 67 (58 percent) patients, adequate in 19 (16.5 percent), and poor in
      29 (25.5 percent). In the group with previous sphincter repair, the outcome was
      good in 18 patients (50 percent), adequate in 4 (11 percent), and poor in 14 (39
      percent; P = 0.2646). The mean resting pressure increased from 20 (range, 3-43)
      mmHg to 24 (range, 10-44) mmHg and from 27 (range, 4-56) mmHg to 32 (range, 16
      45) mmHg, respectively. The mean squeeze pressure increased from 60 (range, 23
      63) mmHg to 67 (range, 33-114) mmHg and from 54 (range, 25-90) mmHg to 70 (range,
      34-95) mmHg, respectively. CONCLUSION: Previous sphincter repair does not affect
      clinical outcome. Repeat anterior overlapping sphincter repair yields a
      significant improvement in the continence score and should be considered as the
      treatment of choice in patients with fecal incontinence who have had previous
      sphincter repair and residual anterior sphincter damage.

PMID- 12004214
TI  - Rectal wall properties in patients with acute and chronic spinal cord lesions.
AB  - PURPOSE: Most patients with spinal cord injuries suffer from constipation or
      fecal incontinence. This study was designed to observe rectal wall properties and
      the rectoanal inhibitory reflex in patients with acute and chronic spinal cord
      injury. METHODS: Rectal wall properties were studied by rectal impedance
      planimetry, a method for simultaneous registration of pressure and rectal cross
      sectional area during distention. Twenty-five patients with spinal cord injury
      (14 with supraconal lesions and 11 with conal/cauda equina lesions) were studied
      one to four weeks after injury, and 17 were available for follow-up after 6 to 14
      months. Results were compared with 15 healthy volunteers. RESULTS: Rectal tone
      was significantly higher (P < 0.05) than normal in patients with acute and
      chronic supraconal lesions but significantly lower (P < 0.05) in patients with
      acute and chronic conal/cauda equina lesions. The proportion of subjects with
      single giant rectal contractions was significantly higher than normal (33
      percent) after acute supraconal spinal cord injury (77 percent; P = 0.02) but not
      after acute conal/cauda equina lesions (45 percent; P = 0.69). Phasic giant
      contractions only occurred in patients with spinal cord injury (once or more in 8
      of 25 patients), but they were not correlated with the level of the lesion.
      Rectal tone and the number of giant rectal contractions did not change
      significantly from the acute to the chronic phase of spinal cord injury. The
      amplitude of the rectoanal inhibitory reflex at distention pressures of 5 and 10
      cm H2O was significantly lower than normal in patients with acute and chronic
      conal/cauda equina lesions (acute, -5 and 44 percent vs. 37 and 82 percent (P <
      0.05); chronic, 6 percent (P < 0.05) and 66 percent (P = NS)) but not in patients
      with supraconal spinal cord injury (acute, 32 and 83 percent; chronic, 61 and 85
      percent (all P = NS)). CONCLUSION: Rectal tone is stimulated by the sacral spinal
      cord but inhibited by supraspinal centers within the central nervous system.
      Likewise, rectal contractility is inhibited by supraspinal centers, and the
      rectoanal inhibitory reflex is stimulated by the sacral spinal cord. Alterations
      caused by either type of spinal cord lesion are present after one to four weeks
      and do not change significantly within the first year.

PMID- 12004215
TI  - Anal fissure and thrombosed external hemorrhoids before and after delivery.
AB  - PURPOSE: Thrombosed external hemorrhoids and anal fissures are common and are
      responsible for severe discomfort during childbirth. However, the real incidence
      of these lesions is unknown. The aim of our study was to evaluate their incidence
      and the risk factors for these lesions during childbirth. METHODS: A prospective
      study with proctologic examination during the last 3 months of pregnancy and
      after delivery (within 2 months) was performed in 165 consecutive pregnant
      females. RESULTS: Fifteen females (9.1 percent) with anal lesions (13 thrombosed
      external hemorrhoids and 2 anal fissures) were observed during pregnancy. Fifty
      eight females (35.2 percent) with anal lesions (33 thrombosed external
      hemorrhoids and 25 anal fissures) were observed during the postpartum period.
      Ninety-one percent of thrombosed external hemorrhoids were observed during the
      first day after delivery, whereas anal fissures were distributed, with no peak,
      over the two months after delivery. The 2 independent risk factors for anal
      lesions (among obstetric, baby's, and mother's information) were dyschezia, with
      a 5.7 odds ratio (95 percent confidence interval, 2.7-12), and late delivery,
      with a 1.4 odds ratio (95 percent confidence interval, 1.05-1.9). Furthermore,
      many thrombosed external hemorrhoids were observed after superficial perineal
      tears and heavier babies (P < 0.05). Only 1 of the 33 patients with thrombosed
      external hemorrhoids who were observed underwent a cesarean section. CONCLUSION:
      One third of females have thrombosed external hemorrhoids or anal fissures in the
      postpartum period. The most important risk factor is dyschezia. Traumatic
      delivery appears to be associated with thrombosed external hemorrhoids.

PMID- 12004216
TI  - Rhomboid excision and Limberg flap for managing pilonidal sinus: results of 102
      cases.
AB  - PURPOSE: Although many methods of surgical and nonsurgical approaches for
      treatment of pilonidal sinus have been proposed, an optimal treatment modality
      has not been achieved yet. The aim of this study was to determine advantages,
      disadvantages, and long-term results of rhomboid excision and Limberg flap
      procedure. METHOD: One hundred ten patients who had been treated with rhomboid
      excision and Limberg flap procedure for primary or recurrent pilonidal sinus were
      invited to the hospital. One hundred two patients responded and were asked about
      their complaints and satisfaction with treatment. Physical examination was
      performed on each patient, and their hospital records were reviewed. RESULTS:
      Three patients developed seroma with negative bacterial cultures, two patients
      had partial wound dehiscence, and one patient had purulent discharge. Mean length
      of hospital stay was 3.7 days, and mean time to return to normal activity was
      seven days. Five patients developed recurrence (4.9 percent) and except for these
      patients, all of the patients were satisfied with the final result. CONCLUSION:
      Rhomboid excision and Limberg flap procedure can be performed for managing
      primary or recurrent pilonidal sinus with a low complication rate, short hospital
      stay, short time to return to normal activity, and good long-term results.

PMID- 12004217
TI  - Neorectal reservoir is not the functional principle of the colonic J-pouch: the
      volume of a short colonic J-pouch does not differ from a straight coloanal
      anastomosis.
AB  - BACKGROUND: Low anterior resection with coloanal anastomosis prevents a
      definitive stoma in patients with distal rectal cancer. However, imperative stool
      urge, stool fragmentation, prolonged stooling sessions, and minor problems of
      incontinence are frequently observed in the postoperative situation and
      negatively affect quality of life. Therefore, the colonic J-pouch was originally
      constructed to create a stool reservoir. In a randomized, prospective study, the
      short (5 cm) colonic J-pouch was tested for function and continence vs. straight
      coloanal anastomosis. METHODS: Over a period of 30 months, 74 consecutive
      patients (55 males) with rectal cancer in the lower and middle third of the
      rectum were included and randomized into two groups. Anastomosis was performed
      either as a coloanal or a colon-pouch-anal anastomosis. The standardized surgical
      procedure included mobilization of the left hemicolon, central ligation of the
      inferior mesenteric artery and vein, preaortal lymph node dissection, autonomic
      nerve preservation, and total mesorectal excision. The anastomosis was performed
      at the upper anal canal or at the intersphincteric level. All patients were
      evaluated preoperatively and six months postoperatively for fecal continence,
      including sphincter manometry and defecation habits. In addition, quality of life
      was determined by use of a standardized questionnaire (European Organization for
      Research and Treatment of Cancer, EORTC-QLQ-C30). RESULTS: Thirty-seven patients
      were randomized into each group. In general, problems with continence for liquids
      or gas occurred less frequently in the colonic J-pouch group 6 months after
      surgery. The frequency of bowel movements was lower in the J-pouch group (2.5 per
      day) than in the coloanal group (4.7 per day). Importantly, in a manometric study
      at the same postoperative point, neorectal capacity was decreased to a similar
      degree in both groups compared with the preoperative rectal volume. Thus, the
      expected and postulated reservoir effect could not be achieved by forming a 5-cm
      colonic J-pouch. CONCLUSION: The colonic J-pouch was superior with regard to
      continence for gas and liquids compared with a straight coloanal anastomosis.
      Furthermore, stool frequency was significantly lower in the J-pouch group than in
      the coloanal reconstruction group. However, because neorectal capacity decreased
      equally in both groups, we speculate that the advantage of the colonic J-pouch is
      not in the creation of a larger neorectal reservoir but rather may be related to
      decreased motility.

PMID- 12004218
TI  - Role of resting pressure gradient in the investigation of idiopathic fecal
      incontinence.
AB  - PURPOSE: One-third of patients who suffer from idiopathic fecal incontinence are
      found to have maximum mean resting pressures within the normal range. The
      objective of this study was to determine whether measuring the gradient of
      pressure at rest throughout the anal canal is a more sensitive predictor of
      incontinence in these patients. METHODS: Anorectal physiology measurements were
      retrospectively reviewed in patients referred over an 18-month period. Two
      patient groups were selected for the study: Group 1, continent patients (n = 80);
      and Group 2, patients with idiopathic fecal incontinence (n = 47). Maximum
      resting pressures, vector volumes, and resting pressure gradients were all
      contrasted, sensitivities and specificities were calculated, and receiver
      operating characteristic curve analyses were performed. Reproducibility studies
      were also performed for the calculation of the pressure gradient. RESULTS:
      Patient demographics were similar in the two groups. The resting pressure
      gradient, maximum mean resting pressure, and vector volumes were significantly
      lower in incontinent patients compared with the normal patients (P < 0.0001, all
      comparisons). The sensitivity (and specificity) of resting pressure gradient,
      maximum mean resting pressure, and vector volumes were 89 percent (96 percent),
      55 percent (98 percent), and 53 percent (88 percent), respectively. CONCLUSION:
      The resting pressure gradient is the most accurate in detecting fecal
      incontinence. The authors conclude that this test is simple, reproducible, and
      identifies an abnormality in the majority of patients with idiopathic fecal
      incontinence.

PMID- 12004219
TI  - The role of hMLH1 methylation in the development of synchronous sporadic
      colorectal carcinomas.
AB  - PURPOSE: AB. B. subset of sporadic colorectal carcinomas show microsatellite
      instability, usually as a result of biallelic hMLH1 gene promoter methylation.
      Synchronous tumors occur in up to 5 percent of patients with colorectal cancer,
      but their cause is poorly understood. We hypothesized that in the setting of
      sporadic microsatellite instability cancers, synchronicity may reflect a global
      predisposition of colorectal epithelium toward tumor development because of gene
      hypermethylation. METHODS: We identified 14 individuals with 33 synchronous
      cancers from a series of 362 patients with 381 sporadic colorectal cancers. We
      then analyzed the synchronous lesions for microsatellite status, hMLH1 protein
      expression, and hMLH1 promoter methylation. RESULTS: Seven of 33 synchronous
      tumors (21 percent) showed microsatellite instability, compared with 36 of 348
      solitary tumors (10.3 percent, P = 0.06). The 14 patients with synchronous tumors
      were significantly older than those with solitary tumors (mean age 79.4 vs. 68.2
      years, P = 0.01), and 5 of these patients had at least one microsatellite
      instability tumor. However, only one patient harbored synchronous tumors that
      were all of the microsatellite instability type. Methylation of the hMLH1
      promoter was seen in 9 synchronous cancers from 27 assessable lesions in 7
      patients and was associated with microsatellite instability (P = 0.01), right
      sidedness (P = 0.01), and loss of expression of hMLH1 (P = 0.03). Only one case
      showed methylation in all synchronous tumors, whereas in five cases synchronous
      tumors showed different methylation status within the one individual. CONCLUSION:
      Our data suggest that synchronous tumors arise as independent events and that the
      slightly greater frequency of synchronous tumors in individuals with
      microsatellite instability cancers is likely to be a chance event reflecting the
      older age of these individuals rather than arising from a predisposition toward
      cancer as a result of global hypermethylation of colorectal epithelium.

PMID- 12004220
TI  - Colorectal cancer mortality in first-degree relatives of early-onset colorectal
      cancer cases.
AB  - PURPOSE: Estimates of familial colorectal cancer risks are useful in genetic
      counseling and as a guide to determining entry into screening programs and trials
      of chemoprevention. Furthermore, they provide an insight into the contribution of
      the known colorectal cancer genes to the familial risk of the disease. There is a
      paucity of data about the familial colorectal cancer risk associated with early
      onset disease outside the recognized cancer predisposition syndromes. METHODS:
      This was a retrospective cohort study. The parents and siblings of 205 patients
      with colorectal cancer aged less than 55 years at diagnosis were studied for
      mortality and cancer incidence. RESULTS: The overall standardized mortality ratio
      of colorectal cancer compared with the Northern Irish population was 3.54 (95
      percent confidence interval, 2.59-4.79). There was some evidence that a family
      history of colorectal cancer is associated with a greater risk of colon (4.16; 95
      percent confidence interval, 2.83-5.91) rather than rectal cancer (2.62; 95
      percent confidence interval, 1.43-4.40). Risks in parents (2.54; 95 percent
      confidence interval, 1.45-3.72) were lower than in siblings (6.15; 95 percent
      confidence interval, 3.90-9.23). CONCLUSION: First-degree relatives of patients
      with early-onset disease are at a marked increase in risk. There is evidence that
      risks vary depending on the type of affected relative and by the site of
      colorectal cancer. This information should be considered in formulating screening
      strategies.

PMID- 12004221
TI  - Adenocarcinoma in the anal canal after ileal pouch-anal anastomosis for
      ulcerative colitis using a double stapling technique: report of a case.
AB  - A case of adenocarcinoma, developed in the anal canal after ileal pouch-anal
      anastomosis for ulcerative colitis using a double stapling technique, is
      reported. In this case a T3N0 cecal cancer was found unexpectedly in the
      colectomy specimen. Two years later, this patient presented with an outlet
      obstruction of the pouch because of development of an adenocarcinoma of the anal
      canal. This was treated with an abdominoperineal excision of the pouch and
      anorectum.

PMID- 12004223
TI  - Depressed-type submucosal colon cancer: report of a case.
AB  - PURPOSE: The article presents one of very few Korean reports on the detection of
      depressed early colorectal cancers, which have been cited by some Japanese
      doctors as another pathway for the development of colon cancers. Depressed-type
      early colorectal cancers have mainly been reported in Japan, and recently a few
      have also been reported in Western countries. Depressed early colorectal cancers
      are still rarely detected in Korea, where most colorectal surgeons, endoscopists,
      and radiologists refer to Western guidelines. METHODS: Recently, the authors
      experienced a typical 12-mm depressed-type early colon cancer in the ascending
      colon of a 55-year-old Korean male patient. It was detected by a colonoscopic
      examination. RESULTS: The lesion was flexible on insufflation and deflation with
      air and was considered an early colon cancer. Because of the large size, a
      surgical resection was performed. The final pathologic result was a minimally
      invasive submucosal cancer without lymph node metastasis. CONCLUSION: This Korean
      case is one of very few reported abroad, so we think that it might make an
      important contribution to research on depressed-type early colorectal cancer.

PMID- 12004225
TI  - Spontaneous transvaginal small-bowel evisceration after perineal proctectomy:
      report of a case and review of the literature.

PMID- 12004226
TI  - The application of percutaneous endoscopic colostomy to the management of
      obstructed defecation.
AB  - PURPOSE: We describe the case of a 52-year woman with a 17-year history of
      obstructed defecation in whom all other standard treatments had failed and the
      patient had refused a colostomy. Her symptoms were controlled by percutaneous
      endoscopic colostomy with antegrade colonic irrigation. METHOD: A percutaneous
      endoscopic colostomy tube was placed in the sigmoid colon endoscopically using a
      colonoscope and the patient irrigated two liters of water through the
      percutaneous endoscopic colostomy twice each day and was able to successfully
      evacuate her rectum without excess straining or discomfort. CONCLUSION:
      Percutaneous endoscopic colostomy is an alternative option to colostomy in the
      management of obstructed defecation.

PMID- 12004227
TI  - Modified perianal incisions in graciloplasty for fecal incontinence.

PMID- 12004228
TI  - Laparoscopy-assisted loop ileostomy: an acceptable option for temporary fecal
      diversion after anorectal surgery.
AB  - PURPOSE: Temporary fecal diversion may be desired after many anorectal
      procedures. The aim of this study was to describe a technique for laparoscopy
      assisted creation of a loop ileostomy in patients undergoing anorectal and
      perineal surgery and to relate short-term outcomes. METHODS: A retrospective
      review of the medical records of 53 consecutive patients who underwent
      laparoscopy-assisted creation of a loop ileostomy as an adjunct to anorectal or
      perineal surgery between 1993 and 1999 was performed. Data were obtained for age
      of the patient, previous abdominal surgical procedures, anorectal or perineal
      surgical procedure performed, American Society of Anesthesiology scores,
      operative times for both creation and takedown of the ileostomy, and
      postoperative return of bowel function. RESULTS: The average duration of
      operation for laparoscopy-assisted creation of the loop ileostomy was 47 (range,
      28-75) minutes, with no conversions to laparotomy. All patients were able to
      tolerate a regular diet on the first postoperative day. Closure was accomplished
      69 (range, 63-96) days later with an average operative time of 52 (range, 35-90)
      minutes. One patient developed ileus after takedown of his stoma. The other 52
      patients were able to tolerate a regular diet by the second postoperative day.
      CONCLUSION: Laparoscopy-assisted creation of a loop ileostomy is an effective
      method for temporary fecal diversion in patients undergoing anorectal surgery.

PMID- 12004229
TI  - Side-to-side isoperistaltic strictureplasty in the treatment of diffuse Crohn's
      disease.

PMID- 12004230
TI  - Electrophysiologic testing of pelvic floor: some remarks.

PMID- 12004231
TI  - Endoanal ultrasound in perianal abscesses.

PMID- 12004232
TI  - Proceedings of the Third Margaux Conference on Critical Illness: the Endothelium-
      an Underrecognized Organ in Critical Illness? Sedona, Arizona, USA. November 14
      18, 2001.

PMID- 12004233
TI  - Endothelial cell dynamics and complexity theory.
AB  - OBJECTIVE: To apply complexity theory to understanding endothelial cell function
      in health and disease. DATA SOURCES AND STUDY SELECTION: Published research and
      review articles in the English language related to complexity theory and
      endothelial cell biology. DATA EXTRACTION AND SYNTHESIS: The results of published
      studies have been used to generate a hypothesis of nonlinear dynamics in
      endothelial cell biology. CONCLUSIONS: The endothelium displays nonlinear
      complexity. I propose a model in which healthy endothelium retains a broad range
      of responses and is therefore highly active, whereas dysfunctional endothelium
      becomes locked into a narrow range of responses, approaching a single steady
      state and eventual quiescence. These concepts lay a foundation for understanding
      the pathophysiology of endothelial cell dysfunction in the multiple organ
      dysfunction syndrome.

PMID- 12004234
TI  - Oxidative stress and endothelial activation.
AB  - The vascular endothelial surface is a major target of oxidative stress, but we
      are only now beginning to understand the molecular sources and physiologic
      consequences of such oxidative activity. Along with exogenous oxidants, provided
      by professional phagocytes or circulating enzymes, vascular cells generate
      oxidants in response to cytokine and growth factor stimulation, and these
      endogenous oxidants participate in vascular cell signal transduction. Endothelial
      cells express at least four of the five principal subunits of an NADPH oxidase,
      and we review evidence that such an oxidase is tightly regulated in both activity
      and in subcellular targeting. Both of these features are likely to contribute to
      the signal specificity of unstable oxidants.

PMID- 12004235
TI  - Shear stress and endothelial cell activation.
AB  - We have shown previously that ischemia in an isolated rat lung that is normally
      oxygenated by continued ventilation results in lipid and protein oxidation,
      indicating the generation of reactive oxygen species. By using a variety of
      biochemical and imaging techniques, we determined that the initial response,
      which occurs within the first second of ischemia, is partial depolarization of
      the endothelial cell plasma membrane. This event is followed within several
      seconds by activation of endothelial NADPH oxidase and generation of superoxide
      anion at the extracellular surface of the cell membrane where it is dismutated to
      freely diffusible H2O2. Approximately 15 secs after the onset of ischemia, we
      detected an elevation of intracellular Ca2+ caused by its release from
      intracellular stores, followed by Ca2+ influx, possibly through T-type voltage
      dependent Ca2+ channels. Increased nitric oxide generation through activation of
      endothelial nitric oxide synthase is detected after about 45 secs of ischemia.
      These changes (endothelial membrane depolarization, reactive oxygen species
      production, elevation of intracellular Ca2+ levels, and nitric oxide generation)
      were confirmed in isolated endothelial cells that had been adapted to shear
      stress in vitro. The in vitro model also demonstrates reactive oxygen species
      dependent activation of nuclear factor-kappaB and activator protein-1 and that 24
      hrs of ischemia results in increased cell division. These results indicate a
      novel cell-signaling pathway in response to loss of shear stress. The basis for
      these changes in endothelial function is related to mechanotransduction, i.e.,
      altered shear stress rather than a metabolic response to ischemia. The biological
      function for the response may be an attempt to restore blood flow through
      vasodilatation and new capillary formation.

PMID- 12004236
TI  - Endothelial responses to mechanical stress: where is the mechanosensor?
AB  - OBJECTIVE: The endothelium is normally subjected to mechanical deformation
      resulting from shear stress and from strain associated with stretch of the vessel
      wall. These stimuli are detected by a mechanosensor that initiates a variety of
      signaling systems responsible for triggering the functional responses. The
      identity of the mechanosensor has not been established. This article discusses
      the different mechanisms of mechanosensing that have been proposed and reviews
      the literature with respect to signaling systems that are activated in response
      to stress and strain in endothelium. DATA SOURCES: Published literature related
      to mechanotransduction, signal transduction pathways initiated by strain in
      endothelium, and pathophysiologic effects of abnormal shear forces in diseases.
      DATA EXTRACTION AND SYNTHESIS: Proposed mechanisms of mechanosensing include
      stretch-sensitive ion channels, protein kinases associated with the cytoskeleton,
      integrin-cytoskeletal interactions, cytoskeletal-nuclear interactions, and
      oxidase systems capable of generating reactive oxygen species. However, the
      molecular identity of the mechanosensor is not known, nor is it clear whether
      multiple sensing mechanisms exist. CONCLUSIONS: Many responses are initiated in
      cells subjected to mechanical deformation, including alterations in ion channel
      conductance, activation of signal transduction pathways, and altered expression
      of specific genes. Future progress in this field will require a critical
      distinction between cell systems that become activated during mechanical strain
      and the identity of the cellular mechanosensor that triggers subsequent
      responses.

PMID- 12004237
TI  - Innate immune recognition of lipopolysaccharide by endothelial cells.
AB  - OBJECTIVE: The endothelium is an active component of the innate immune response
      to bacterial invasion. Endothelial cells comprise mechanisms to recognize
      structural patterns expressed by pathogens and subsequently initiate the
      transcription of inflammatory genes. The purpose of this article is to summarize
      the molecular processes that underlie the endothelial innate immune response to
      microbial components, with a particular focus on responses to Gram-negative
      bacterial lipopolysaccharide. DATA SOURCES: Personal observations and review of
      the literature as revealed by the National Library of Medicine. DATA SUMMARY AND
      CONCLUSION: Endothelial cells recognize the presence of microbial components such
      as lipopolysaccharide via a receptor complex that contains at least three
      important cell surface components: CD14, Toll-like receptor-4, and MD-2. CD14 and
      MD-2 exist as soluble receptor components and are thought to bind to both
      lipopolysaccharide and Toll-like receptor-4, whereas Toll-like receptor-4 itself
      is the transmembrane signal transducer. Single-point mutations in MD-2 or the
      cytoplasmic portion of Toll-like receptor-4 abrogate the response to
      lipopolysaccharide. The composition of this receptor and the recruitment and
      activation of various cytoplasmic proteins afford at least five levels of ligand
      specificity and suggest that there are at least as many potential therapeutic
      targets for Toll-like receptor-mediated inflammatory states, including sepsis.

PMID- 12004238
TI  - Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy.
AB  - OBJECTIVE: This review describes efforts to develop therapies directed at
      leukocyte and endothelial adhesion molecules for the treatment of acute and
      chronic inflammatory diseases, including hemorrhagic shock. DATA SOURCES AND
      STUDY SELECTION: Published research and review articles and Web sites relating to
      the clinical use of drugs directed to leukocyte or endothelial cell adhesion
      molecules. DATA EXTRACTION AND SYNTHESIS: The results of relevant studies of
      adhesion blockade are reviewed. Trials in putative clinical ischemia-reperfusion
      disorders, particularly traumatic shock, are emphasized. Trials are designated as
      positive or negative, depending on whether the primary end points established by
      the trial investigators were met. CONCLUSIONS: Blockade of leukocyte adhesion to
      endothelium by monoclonal antibodies or other antagonists has been demonstrated
      to reduce vascular and tissue injury in a wide variety of animal models of
      inflammatory and immune disease. Anti-adhesion therapy directed at lymphocyte
      trafficking has shown efficacy in several phase 2 and 3 clinical trials in
      inflammatory bowel disease, multiple sclerosis, and psoriasis. Despite strong
      preclinical data, results of phase 2 and 3 trials of neutrophil adhesion blockade
      in putative ischemia-reperfusion disorders-stroke, myocardial infarction, and
      hemorrhagic shock-have been disappointing.

PMID- 12004239
TI  - Endothelium: interface between coagulation and inflammation.
AB  - OBJECTIVE: To review the involvement of endothelial cells in the pathogenesis of
      coagulation abnormalities during severe infection, the differential role of
      proinflammatory cytokines in these mechanisms, and the cross talk between
      coagulation and inflammation. DATA SOURCES: Published articles on experimental
      studies of coagulation activation during inflammation and clinical studies of
      patients with sepsis and associated hemostatic abnormalities. DATA SYNTHESIS AND
      CONCLUSION: The endothelium plays a central role in all major pathways involved
      in the pathogenesis of the hemostatic derangement observed during severe
      inflammation (i.e., initiation and regulation of thrombin generation and
      inhibition of fibrinolysis). Rather than being a unidirectional relationship, the
      interaction between inflammation and coagulation involves significant cross talk
      in which the endothelium seems to play a pivotal role.

PMID- 12004240
TI  - Endothelial cell apoptosis in sepsis.
AB  - OBJECTIVE: To discuss a potential role for endothelial cell apoptosis in the
      pathogenesis of sepsis. DATA SOURCES: Studies published in biomedical journals
      and studies from the authors' laboratory. STUDY SELECTION: In vitro and in vivo
      studies of endothelial cell apoptosis in endotoxin and sepsis models. DATA
      EXTRACTION AND SYNTHESIS: Relevant studies that investigate the role of apoptosis
      in endotoxemia and sepsis are presented. The divergent results of the different
      studies and the potential reasons for the discrepant findings are presented. The
      importance of apoptosis in sepsis and the potential impact on endothelial cells
      and organ function are highlighted. CONCLUSIONS: Apoptosis is an important
      mechanism of lymphocyte and gastrointestinal epithelial cell death in sepsis.
      Although abundant in vitro studies indicate that endothelial cell apoptosis can
      occur in response to certain pathogenic organisms (e.g., Rickettsia rickettsii),
      data documenting endothelial cell apoptosis in in vivo models of sepsis are
      lacking. Because endothelial cells that undergo apoptosis detach from the vessel
      basement membrane, enter the circulation, and are rapidly cleared, it may be
      difficult to detect endothelial cell apoptosis in in vivo models of sepsis. The
      impact of endothelial cell apoptosis in sepsis may either be detrimental or
      beneficial to host survival, depending on the particular pathogen.

PMID- 12004241
TI  - Endothelial cell dysfunction and abnormal tissue perfusion.
AB  - OBJECTIVE: To determine the precise role of the myoendothelial regulatory unit in
      improved tissue perfusion and metabolic regulation. DATA SOURCES AND STUDY
      SELECTION: A review of the published literature (MEDLINE and other original
      articles and reviews) on endothelial cells, vascular reactivity, and tissue
      perfusion. DATA EXTRACTION AND SYNTHESIS: According to the concept of intrinsic
      metabolic regulation, vasodilation in tissues with relatively high metabolic
      rates competes with sympathetic vasoconstrictor tone, thereby adjusting the
      balance between local tissue oxygen supply and demand. Although the nature of the
      oxygen-sensitive structures acting at the local tissue level is not completely
      understood, endothelial cells in direct contact with blood have a number of
      properties that confer the potential to act as effective oxygen sensors. The
      endothelium and smooth muscle of arteries and arterioles seem to be coupled both
      structurally and functionally. Sensing involves local depolarization and
      hyperpolarization of the capillary endothelial cell, and communication is
      achieved by an electronic spread via endothelium-smooth muscle cell-to-cell gap
      junctions. Therefore, during hypoxic challenge, the ability of a tissue to
      extract oxygen-and to minimize shunting through areas with a high rate of
      perfusion relative to their oxygen uptake-may be considered an integrative test
      of endothelium function and microcirculatory coordination. CONCLUSION:
      Endothelial cells seem to play a central role in coordinating the
      microcirculatory system and promoting tissue perfusion and oxygen supply. In a
      pathologic situation such as sepsis, abnormal interendothelial cell coupling and
      an abnormal arteriolar conducted response may account for impaired tissue
      perfusion and abnormal oxygen extraction.

PMID- 12004242
TI  - Endothelial injury and dysfunction in ischemic acute renal failure.
AB  - Ischemic acute renal failure is the most common cause of acute renal failure in
      hospitalized patients and has an average mortality rate of 50%. Although
      epithelial and vascular smooth muscle cell abnormalities have been clearly
      delineated in association with this condition, the extent of endothelial injury
      and dysfunction has been difficult to document, primarily for anatomic reasons.
      However, endothelial tight junction separation and endothelial cell detachment,
      blebbing, and necrosis have been observed after ischemia in other organs. In
      addition, adenosine triphosphate depletion studies in cultured endothelial cells
      have demonstrated that multiple actin-based alterations occur in a reversible and
      duration-dependent fashion. After an ischemic insult, total renal blood flow
      returns toward normal, but marked, regional alterations occur. Most affected is
      the outer medullary or corticomedullary junction region where blood flow remains
      approximately 10% of normal. In this area, the microvasculature becomes
      congested. Interstitial edema, red blood cell trapping, leukocyte adherence, and
      extravasation all contribute to this congestion. Increased expression of both P
      selectin and E selectin has been documented in renal endothelial cells after
      ischemic injury, and treatment with antibodies to either intercellular adhesion
      molecule-1, P selectins, or E selectins has been shown to minimize renal injury.
      During ischemia in vivo and adenosine triphosphate depletion in cell culture
      studies, F-actin destruction occurs, with polymerization leading to accumulation
      of intracellular actin aggregates. By using multiphoton microscopy, Voxx
      software, and the Tie-2 mouse with selective endothelial cell green fluorescent
      protein expression driven by the Tie-2 promoter, we have been able to identify
      macrovascular and microvascular endothelial cells in four dimensions (three
      dimensions plus time) intravitally. By using Texas red-labeled large molecular
      weight dextrans, we can document blood flow and vascular dysfunction. Intravital
      studies using multiphoton imaging techniques can now be conducted to identify and
      quantify endothelial cell injury and dysfunction in functioning organs.

PMID- 12004243
TI  - Evolving role of tissue factor and its pathway inhibitor.
AB  - OBJECTIVE: To review the experimental and clinical evidence of the emerging role
      of tissue factor in intravascular thrombosis and to examine evidence supporting
      the potential use of tissue factor pathway inhibitor as an antithrombotic
      therapeutic agent. DATA SOURCES AND STUDY SELECTION: A PubMed search was
      conducted encompassing articles in the English language relating to tissue factor
      and tissue factor pathway inhibitor in intravascular coagulation. CONCLUSIONS:
      Tissue factor, a membrane-bound procoagulant glycoprotein, is the initiator of
      the extrinsic clotting cascade, which is the predominant coagulation pathway in
      vivo. The traditional view localizes tissue factor to extravascular sites, where
      it remains sequestered from circulating factor VII until vascular integrity is
      disrupted or until tissue factor expression is induced in endothelial cells or
      monocytes. This perspective has been challenged since the discovery of tissue
      factor antigen in plasma, on circulating microparticles, and on leukocytes in
      whole blood. Recently, the apparent role of tissue factor has expanded with the
      demonstration that this molecule also functions as a signaling receptor.
      Recombinant tissue factor pathway inhibitor, an analogue of the physiologic
      inhibitor of tissue factor, is a potent inhibitor of thrombus formation in
      experimental models. In summary, the tissue factor pathway initiates thrombosis
      in vivo. In addition to its classic tissue-bound distribution, recently
      discovered blood-borne tissue factor may have an important procoagulant function.
      Despite showing promise in early human studies, a recently completed phase 3
      trial of recombinant tissue factor pathway inhibitor in severe sepsis failed to
      show a reduction in the primary end point of 28-day all-cause mortality. Tissue
      factor pathway inhibitor, however, remains a plausible therapeutic agent in other
      conditions of increased thrombogenicity, such as acute coronary syndromes, and
      further studies to examine this potential are warranted.

PMID- 12004244
TI  - Janus face of vascular endothelial growth factor: the obligatory survival factor
      for lung vascular endothelium controls precapillary artery remodeling in severe
      pulmonary hypertension.
AB  - Vascular endothelial growth factor (VEGF) plays a central role in the life and
      death of pulmonary vascular endothelial cells. Treatment of neonatal or adult
      rats with a VEGF receptor blocker destroys lung capillaries by inducing
      endothelial cell apoptosis and causes emphysema. Human lung tissue samples from
      patients with endstage emphysema have decreased levels of VEGF messenger RNA and
      protein and have decreased expression of kinase insert domain-containing receptor
      (VEGF receptor II). These decreases are associated with a high rate of alveolar
      septal cell apoptosis, indicating perhaps that decreased VEGF and kinase insert
      domain-containing receptor expression impairs endothelial cell survival in
      emphysematous lungs. Combination of VEGF receptor blockade with chronic hypoxia
      (3-wk exposure) results in obliteration of small precapillary pulmonary arteries
      by proliferating endothelial cells, severe pulmonary hypertension, and death
      caused by right-side heart failure. We propose that 1) VEGF receptor blockade
      causes endothelial cell apoptosis, 2) hypoxic vasoconstriction (shear stress)
      selects apoptosis-resistant endothelial cells that proliferate and obliterate the
      lumen, and 3) the vascular remodeling observed is relevant to the structural
      alterations that characterize severe pulmonary hypertension (including primary
      pulmonary hypertension) in humans. The endovascular cell growth in human disease
      and in our model exhibits some similarities with neoplastic cell growth.
      Chemotherapy strategies can now be employed in the animal model in an attempt to
      treat established vascular-obliterative lung disease.

PMID- 12004245
TI  - Multiple organ dysfunction syndrome in hematopoietic stem cell transplantation.
AB  - OBJECTIVE: To review the data demonstrating that central nervous system,
      pulmonary, and hepatic dysfunctions during hematopoietic stem cell
      transplantation have similar laboratory correlates and clinical outcomes,
      suggesting that they are individual organ manifestations of a systemic disorder
      at presentation, a disorder similar to the multiple organ dysfunction syndrome
      seen in other populations of critically ill patients. DATA SOURCES AND STUDY
      SELECTION: Reports of clinical research studies on the natural history and
      laboratory correlates of central nervous system, pulmonary, and hepatic
      dysfunction (generally manifesting as the syndrome of hepatic veno-occlusive
      disease) during hematopoietic stem cell transplantation. DATA EXTRACTION AND
      SYNTHESIS: During hematopoietic stem cell transplantation, pulmonary dysfunction
      (manifesting as hypoxia), central nervous system dysfunction (detected by
      alteration of the Mini-Mental Status Exam), and hepatic dysfunction (presenting
      as the syndrome of hepatic veno-occlusive disease) are all associated with
      significant decreases in the levels of antithrombin III and protein C and an
      increase in the platelet transfusion requirement. Each of these three organ
      dysfunctions is associated with a high likelihood of being followed by the other
      two and, eventually, death. Patients with these organ dysfunctions have higher
      levels of interleukin-6, interleukin-10, and tumor necrosis factor-alpha than
      patients who never develop these complications. Mortality rates for patients with
      these organ dysfunctions vary from 15% in patients with only one organ
      dysfunction to 100% in patients who have progressed to all three. Patients who
      develop none of these organ dysfunctions have a mortality rate that approaches
      zero. CONCLUSIONS: Central nervous system, pulmonary, and hepatic dysfunctions
      are intimately involved in the mortal complications of hematopoietic stem cell
      transplantation. Because these organ dysfunctions have similar correlates and
      similar outcomes, the hypothesis that they are individual parts of a systemic
      disorder is proposed. The additional observation that these organ dysfunctions
      are associated with abnormally high levels of inflammation-related cytokines
      raises the possibility that their pathogenesis is similar to that of multiple
      organ dysfunction syndrome in other populations of critically ill patients.

PMID- 12004246
TI  - Migration inhibitory factor in the cerebral and systemic endothelium in sepsis
      and malaria.
AB  - OBJECTIVE: We have included migration inhibitory factor (MIF) in an ongoing
      immunohistochemical study comparing the site and intensity of the generation of
      inflammatory mediators in falciparum malaria, sepsis, and other causes of
      pediatric death in Africa. We wanted to determine whether it could account for
      our observation that inducible nitric oxide synthase is less strongly induced in
      the cerebral, compared with the systemic, vasculature. DATA SOURCES: Comparisons
      of tissue samples taken from blood vessel walls from the brain and the axillary
      space in a series of sepsis and falciparum malaria autopsies of African children.
      DATA SUMMARY: Intense staining for MIF has been detected in endothelial cells of
      axillary region vessels of all sepsis cases and most of the malaria cases
      examined. This parallels our findings with inducible nitric oxide synthase
      staining. African and Western control tissues from noninfectious causes of death
      stained lightly or not at all. In contrast, MIF could not be detected in vascular
      endothelial cells within the brain, where inducible nitric oxide synthase
      staining was much less intense. Detection of both MIF and inducible nitric oxide
      synthase in ependymal and glial cells in the same brains served as an internal
      positive staining control. CONCLUSION: These outcomes add weight to the proposal
      that endothelial cells are a site of intense inflammatory mediator activity in
      sepsis and malaria. They also suggest that suppression of anti-inflammatory
      glucocorticoids by MIF may be lower in the brain than elsewhere in the body. The
      lack of MIF in cerebral vasculature endothelial cells may be linked to the
      absence of thrombomodulin in these cells. The systemic cellular distribution and
      intensity of MIF in human systemic inflammatory states has not been described.

PMID- 12004247
TI  - Role of the endothelium in viral hemorrhagic fevers.
AB  - OBJECTIVE: To describe endothelial participation in the pathogenesis of viral
      hemorrhagic fevers and certain other acute infectious diseases. DATA EXTRACTION
      AND SYNTHESIS: Survey of published literature on viral hemorrhagic fevers
      interpreted in light of observations in patients and research on those diseases.
      CONCLUSIONS: Endothelial involvement is an extremely important factor in the
      clinical syndrome termed viral hemorrhagic fever. Endothelial dysfunction is
      important in the genesis of bleeding, which is not universal and is commonly seen
      only in the presence of thrombocytopenia or severe platelet dysfunction. The
      pathogenesis of endothelial dysfunction varies in the different diseases. In some
      situations, direct endothelial infection is important in increased vascular
      permeability, changes in the procoagulant vs. anticoagulant balance, or cytokine
      production. In all the viral hemorrhagic fevers studied to date, cytokine
      induction is an important factor and also acts on the endothelium. Poor
      myocardial contractility is a very important issue in viral hemorrhagic fever and
      is not caused by direct viral infection of the heart; it is increasingly being
      recognized that these patients present with low cardiac output and high
      peripheral resistance and that they respond poorly to fluid infusion. The
      clinical findings in viral hemorrhagic fever differ from those in the sepsis
      syndrome and should be studied and interpreted separately; this approach will
      sharpen therapeutic approaches and could shed light on the problems of sepsis in
      general.

PMID- 12004248
TI  - Endothelium and disordered fibrin turnover in the injured lung: newly recognized
      pathways.
AB  - OBJECTIVES: To review derangements of pathways of fibrin turnover that promote
      pathologic fibrin deposition in the acute respiratory distress syndrome and to
      review the contribution of the endothelium and parenchymal lung cells to the
      derangements. In addition, to review how these pathways can be exploited in
      specific clinical circumstances, including sepsis and acute lung injury. Lastly,
      to review newly recognized posttranscriptional and urokinase-dependent pathways
      by which the fibrinolytic system is regulated in the lung. DATA SOURCES: Medical
      literature published in English from 1966 to present. DATA SUMMARY: Local
      abnormalities of fibrin turnover in the injured lung recapitulate the systemic
      changes observed in sepsis. In both circumstances, the procoagulant response is
      increased, whereas fibrinolytic activity is concurrently depressed. The increased
      procoagulant activity is related to tissue factor associated with factor
      VII/VIIa. Fibrinolytic activity in the vasculature is mainly attributable to
      tissue plasminogen activator, whereas extravascular fibrinolytic activity in the
      lung is mainly attributable to urokinase plasminogen activator (uPA). Depressed
      fibrinolytic activity is in large part attributable to plasminogen activator
      inhibitor-1. In sepsis, activated protein C is also deficient, potentiating the
      inflammatory response, coagulopathy, and depressed fibrinolysis. Recombinant
      human activated protein C (drotrecogin alfa [activated]) was successful as an
      intervention for sepsis in a recent phase 3 clinical trial (PROWESS). Recently,
      novel posttranscriptional pathways that regulate expression of uPA, its receptor
      (uPAR), and plasminogen activator inhibitor-1 have been identified. The
      responsible mechanisms involve cis-trans interactions between newly recognized
      messenger RNA (mRNA) binding sequences and mRNA binding proteins. A 51 nucleotide
      mRNA binding sequence within the coding region of uPAR mRNA interacts with a
      novel 50-kDa mRNA binding protein to destabilize the message. Sequences within
      the 3' untranslated region of uPA or plasminogen activator inhibitor-1 mRNA
      interact with 30- and 60-kDa proteins, respectively, to regulate message
      stability. All of these pathways operate in lung epithelial cells, and
      endothelial cells regulate uPA expression through a similar pathway. In addition,
      uPA itself is capable of inducing expression of other components of the
      fibrinolytic system, including uPAR. This observation defines another feedback
      loop that could amplify local fibrinolysis and other uPA- or uPAR-mediated
      cellular responses, including cellular proteolysis, proliferation, and directed
      cellular migration. CONCLUSIONS: Novel posttranscriptional pathways regulate
      expression of uPA, uPAR, and plasminogen activator inhibitor-1. uPA itself is
      capable of inducing other components of the fibrinolytic system. Some or all of
      these newly recognized pathways are operative in endothelial and parenchymal lung
      cells and may influence disordered fibrin turnover in the injured lung.

PMID- 12004249
TI  - Neutrophil elastase and acute lung injury: prospects for sivelestat and other
      neutrophil elastase inhibitors as therapeutics.
AB  - OBJECTIVES: To review the evidence and rationale that suggest that neutrophil
      elastase (NE) may contribute to the development of acute lung injury (ALI) and
      the acute respiratory distress syndrome. To review selected preliminary data
      regarding the effectiveness of NE inhibition in animals, in in vitro models, and
      in patients with ALI. DATA SOURCES: The published literature and observations
      provided by Ono Pharmaceutical and Eli Lilly investigators and their colleagues.
      DATA SUMMARY: Taken en toto, the data suggest that NE could contribute to ALI and
      endothelial cell injury that is relevant to ALI. Moreover, the toxic effects of
      NE are greatly enhanced by increased oxidative stress, which commonly occurs in
      patients with ALI. In addition to neutrophils, xanthine oxidase, a constituent of
      endothelial cells, is a potential source of oxidative stress in ALI; xanthine
      oxidase-derived oxidants enhance NE toxicity in in vivo, isolated lung, and in
      vitro endothelial cell test systems. Not surprisingly, endogenous nonoxidatively
      sensitive NE inhibitors (e.g., eglin C) are more effective in combating the
      detrimental effects of NE than oxidatively sensitive NE inhibitors (e.g., alpha-1
      proteinase inhibitor). In addition, a synthetic NE inhibitor, sivelestat (ONO
      5046 and LY544349), is effective in reducing measures of inflammation and injury
      in multiple animal models of ALI. In a trial of ALI patients with systemic
      inflammatory response syndrome, conducted in Japan by Ono Pharmaceutical
      scientists, sivelestat treatment improved the investigator assessment of global
      improvement and the percentages of patients who were removed from ventilators and
      transferred out of the intensive care unit. CONCLUSIONS: Further study of the
      role of NE inhibition as a treatment for ALI is warranted. Additional clinical
      and preclinical studies with sivelestat and various other NE inhibitors should
      not only clarify the clinical potential of this intervention strategy, but also
      better define the activities of NE in inflammatory disorders such as ALI and
      multiple organ failure.

PMID- 12004250
TI  - Recombinant human activated protein C attenuates the inflammatory response in
      endothelium and monocytes by modulating nuclear factor-kappaB.
AB  - OBJECTIVE: To review the anti-inflammatory and anti-apoptotic properties of
      drotrecogin alfa (activated) (recombinant human activated protein C), emphasizing
      its modulatory effects on endothelial nuclear factor-kappaB. We propose a broad
      anti-inflammatory effect of drotrecogin alfa (activated), acting on both
      endothelium and monocytes. DATA SOURCES: A selected review of the published
      literature on nuclear factor-kappaB, severe sepsis, and the use of drotrecogin
      alfa (activated) in clinical and preclinical models, together with data derived
      from preclinical gene profiling of model systems. DATA EXTRACTION AND SYNTHESIS:
      Data from the PROWESS trial support the preclinical evidence of an antithrombotic
      effect of drotrecogin alfa (activated). Anti-inflammatory effects through
      reduction of thrombin generation and through thrombin-independent mechanisms in
      mononuclear and endothelial cells are reviewed. Inhibition of apoptosis is used
      as an example of the protective effect of drotrecogin alfa (activated) on
      endothelial and mononuclear cell dysfunction. CONCLUSIONS: Drotrecogin alfa
      (activated) acts as a modulator of nuclear factor-kappaB to aid in the host
      immune response in endothelium and monocytes. Extrapolation of gene array
      findings to explain apoptosis in endothelium and monocytes, coupled with emerging
      preclinical reports, provides evidence to support the role of drotrecogin alfa
      (activated) in modulating nuclear factor-kappaB.

PMID- 12004251
TI  - The platelet-activating factor signaling system and its regulators in syndromes
      of inflammation and thrombosis.
AB  - OBJECTIVES: To review the platelet-activating factor (PAF) signaling system, its
      regulation, and its dysregulation in acute inflammation and thrombosis and in
      syndromes that involve these cascades, including sepsis. DATA SOURCES: A summary
      of published literature from MEDLINE search files and published reviews. DATA
      EXTRACTION, SYNTHESIS, AND SUMMARY: PAF, a phospholipid signaling molecule,
      transmits outside-in signals to intracellular transduction systems and effector
      mechanisms in a variety of cell types, including key cells of the innate immune
      and hemostatic systems: neutrophils, monocytes, and platelets. Thus, the PAF
      signaling system is a point of convergence at which injurious stimuli can trigger
      and amplify both acute inflammatory and thrombotic cascades. The biological
      activities of PAF are regulated by several precise mechanisms that, together,
      constrain and control its action in physiologic inflammation. Unregulated
      synthesis of PAF or defects in the mechanisms that limit its biological
      activities have the potential to cause pathologic inflammation and thrombosis. In
      addition, nonenzymatic generation of oxidized phospholipids that are recognized
      by the PAF receptor can trigger inflammatory and thrombotic events. There is
      evidence that the PAF signaling system is dysregulated in sepsis, shock, and
      traumatic injury and that interruption or termination of its effector responses
      leads to beneficial outcomes. Plasma PAF acetylhydrolase, an enzyme that
      hydrolyzes PAF and structurally related oxidized phospholipids, yielding products
      that are no longer recognized by the PAF receptor, may be a particularly
      important signal terminator. CONCLUSION: The PAF signaling system can trigger
      inflammatory and thrombotic cascades, amplify these cascades when acting with
      other mediators, and mediate molecular and cellular interactions (cross talk)
      between inflammation and thrombosis. Evidence from in vitro experiments, studies
      of experimental animals, and clinical observations in humans indicates that the
      PAF signaling system is important in sepsis and other syndromes of inflammatory
      injury and that therapeutic strategies to interrupt or terminate signaling via
      the PAF signaling system may be useful in these conditions.

PMID- 12004252
TI  - Markers of endothelial damage in organ dysfunction and sepsis.
AB  - OBJECTIVES: To review the literature on direct and indirect markers of
      endothelial activation and damage in patients with sepsis and systemic
      inflammation and to assess their clinical usefulness for diagnosis and outcome.
      Various markers derived from or activated by endothelial cells are described,
      such as adhesion molecules, thrombomodulin, von Willebrand factor, parameters of
      the coagulation system, and interleukin-6. Furthermore, the association of these
      markers with the severity of sepsis, systemic inflammation, and outcome is
      evaluated. DATA EXTRACTION AND SYNTHESIS: Published research and review articles
      related to these parameters, with special emphasis on clinical studies.
      CONCLUSIONS: Endothelial activation and damage occur early during sepsis and play
      a major role in the pathophysiology of systemic inflammation. Various markers of
      endothelial activation are increased during sepsis and systemic inflammation, and
      in most studies, the level of markers such as soluble intercellular adhesion
      molecule, vascular cell adhesion molecule, and E selectin correlate well with the
      severity of inflammation and the course of the disease. However, to date, it
      remains unclear whether adhesion molecules and coagulation parameters are
      superior in this respect to interleukin-6 and procalcitonin, as direct
      comparisons are lacking. In addition, it is evident that markers of endothelial
      activation and coagulation parameters lack specificity for infection-induced
      endothelial damage and organ dysfunction.

PMID- 12004253
TI  - Platelet function in sepsis.
AB  - OBJECTIVE: To evaluate platelet function in sepsis. DATA SOURCES: The MEDLINE
      database and bibliographies of selected articles. DATA SYNTHESIS: The common
      occurrence of thrombocytopenia in critically ill patients has been recognized for
      many years and is known to be associated with an increased mortality rate.
      Platelet function can be divided into four areas: activation, adhesion,
      aggregation, and secretion. Studies have found that activated platelets secrete
      key components of the coagulation and inflammatory cascades and are involved in
      the regulation of vascular tone. However, studies on platelet function in sepsis
      have been scarce, and their data are often conflicting. In sepsis, aggregation of
      circulating platelets seems to be reduced, yet platelet receptors are present in
      normal amounts. CONCLUSIONS: Platelets play a complex role in sepsis; they are
      able to modulate not only their own function but also that of cells around them.
      Further study is needed to better define the precise mechanisms and effects of
      platelet activation in sepsis and to determine the benefits and risks of
      inhibiting platelet function.

PMID- 12004254
TI  - Soluble thrombomodulin, plasma-derived unactivated protein C, and recombinant
      human activated protein C in sepsis.
AB  - OBJECTIVE: To review the physiologic and biochemical mechanisms and the rationale
      for the use of soluble thrombomodulin, plasma-derived protein C, and recombinant
      human activated protein C in sepsis. DATA SOURCES AND STUDY SELECTION: Research
      and review articles related to the protein C pathway published in English from
      1960 to present. DATA EXTRACTION AND SYNTHESIS: The protein C anticoagulant
      pathway plays a major role in controlling microvascular coagulation and
      inflammation. Protein C is the zymogen of the vitamin K-dependent serine protease
      activated protein C. Protein C is converted to activated protein C when thrombin
      complexes with thrombomodulin, an endothelial surface transmembrane glycoprotein.
      Activated protein C inactivates factors Va and VIIIa and effectively limits
      further thrombin generation. This protein also enhances endogenous fibrinolytic
      activity and modulates the inflammatory response. A rapid depletion of protein C
      occurs in sepsis, which contributes to sepsis-induced coagulopathy and correlates
      with a poor prognosis. The decrease in tissue levels of thrombomodulin in
      patients with meningococcemia suggests that the ability to convert protein C to
      activated protein C may also be compromised. The ability of soluble
      thrombomodulin to block fibrinogen clotting and cell activation, to activate
      protein C, and to promote thrombin inhibition in different animal models suggests
      that soluble thrombomodulin could be a useful therapeutic agent in sepsis.
      However, soluble thrombomodulin is less effective in blocking fibrinogen and
      platelet activation and in promoting thrombin inhibition than endothelial surface
      membrane-bound thrombomodulin. Only activated protein C, and not protein C, has
      clearly shown a reduction in mortality in experimental animal models of sepsis
      and in humans. CONCLUSIONS: The multipotent pharmacodynamic effects
      (antithrombotic, profibrinolytic, and anti-inflammatory) of activated protein C
      may explain why recombinantly derived human activated protein C is the first
      experimental agent to demonstrate a significant survival benefit in patients with
      severe sepsis.

PMID- 12004255
TI  - Antithrombin, heparin, and heparan sulfate.
AB  - OBJECTIVES: To review the experimental and clinical evidence that antithrombin
      has multiple mechanisms for both its anticoagulant and anti-inflammatory
      properties. The interaction between antithrombin and specific polysulfated,
      acidic oligosaccharide moieties found on heparin and related proteoglycan
      molecules within the circulation and on endothelial surfaces will also be
      examined. DATA SOURCES: Review of the literature relating to antithrombin
      published during the past 25 yrs. DATA SUMMARY: Antithrombin is the most abundant
      endogenous anticoagulant circulating in human plasma. This serine protease
      inhibitor participates in the regulation of clotting in both physiologic and
      pathologic states. Reduced antithrombin activity in the early phases of sepsis
      contributes to a procoagulant state with excess activation of the innate immune
      response. Antithrombin binds to specific pentasaccharides expressed on heparin,
      glycosaminoglycans, and related proteoglycans within the circulation and along
      endothelial surfaces. The functions of neutrophils, monocytes, and endothelial
      cells are altered as a result of their interaction with antithrombin. These
      effects are mediated by the enzyme inhibitory action of antithrombin and its
      ability to function as a ligand for antithrombin receptors on cell surfaces. In
      addition, antithrombin exerts anti-inflammatory properties by both prostacyclin
      dependent and prostacyclin-independent actions; heparin interferes with these
      anti-inflammatory properties. The role of antithrombin in sepsis, its therapeutic
      utility in severe sepsis, and its combination with heparin remain the subject of
      considerable debate. The results of a recent phase 3 clinical trials with high
      dose antithrombin in sepsis suggested a beneficial effect in patients who did not
      concomitantly receive heparin, thereby generating new challenges in the
      understanding of interactions between antithrombin and heparin or heparin-like
      proteoglycans. CONCLUSIONS: Antithrombin has complex interactions with host
      coagulopathic and systemic inflammatory responses under physiologic conditions
      and in sepsis. The impact of these interactions in critically ill patients and
      the therapeutic implications of administration of antithrombin, and various doses
      and types of heparin in such patients, need further clarification.

PMID- 12004256
TI  - Platelet glycoprotein IIb/IIIa antagonists: lessons learned from clinical trials
      and future directions.
AB  - Platelets play an important role in the pathophysiology of acute myocardial
      infarction, unstable angina, and ischemic stroke. The expression of the
      glycoprotein IIb/IIIa (alphaIIb/beta3 integrin) receptor on the surface of
      activated platelets constitutes the common pathway for platelet aggregation.
      Glycoprotein IIb/IIIa has low affinity for its soluble ligands (fibrinogen and
      von Willebrand factor) in resting platelets. In the setting of vascular injury,
      platelet activation occurs after binding of the glycoprotein Ib-IX-V receptor to
      von Willebrand factor in the extracellular matrix (at high shear rate) and
      binding of soluble agonists to specific platelet membrane receptors. The ensuing
      inside-out signaling increases several-fold the affinity and avidity of
      alphaIIb/beta3 for its ligands. High affinity ligand binding to alphaIIb/beta3
      triggers outside-in signaling, causing microskeletal contraction and platelet
      retraction. The signaling pathways for inside-out and outside-in signaling are
      incompletely understood. Glycoprotein IIb/IIIa antagonists were developed under
      the premise that these agents would abrogate platelet aggregation while
      preserving platelet monolayer deposition at sites of injury. A number of
      parenteral and oral agents have been developed and evaluated in clinical trials.
      Three of them are approved in the United States and other countries: abciximab
      (ReoPro; the Fab fragment of a chimeric human-mouse antibody), eptifibatide
      (Integrelin; a cyclic heptapeptide), and tirofiban (Aggrastat; a tyrosine-derived
      nonpeptide molecule). The greatest clinical impact of these parenteral agents
      (used in conjunction with aspirin and heparin) has been in the prevention of
      ischemic complications after percutaneous coronary intervention. In contrast,
      oral agents have yielded disappointing results in the secondary prevention of
      acute coronary syndromes, and none of them are approved at present. Eptifibatide
      and tirofiban are specific for alphaIIb/beta3, whereas abciximab also exhibits
      cross-reactivity with the alphavbeta3 and alphaMbeta2 integrins. Although
      alphaIIb/beta3 is unique to platelets and megakaryocytes, alphavbeta3 is more
      widely distributed and mediates several functions, including endothelial cell
      migration, monocyte adhesion, angiogenesis, and inhibition of apoptosis.
      alphaMbeta2 mediates leukocyte-platelet interactions. In the percutaneous
      coronary intervention trials, abciximab has been more efficacious than the other
      parenteral agents, perhaps because of cross-reactivity with these other
      integrins, the pharmacodynamic profile of abciximab, or other effects. Other
      documented effects of abciximab include acute dethrombosis, reduction of thrombin
      generation, and improved flow in the coronary microcirculation after percutaneous
      coronary intervention. Abciximab is presently under evaluation in the treatment
      of acute ischemic stroke. Promising data have been obtained in experimental
      models of tumor angiogenesis and sickle cell anemia.

PMID- 12004257
TI  - The era of genomics: impact on sepsis clinical trial design.
AB  - OBJECTIVE: This article aims to address the predictable impact of genetics on the
      design of clinical trials in the field of critical care medicine, with emphasis
      on the pathophysiology of sepsis and its treatment. DATA SOURCES: Published
      articles reporting studies on sepsis and septic shock or assessing the influence
      of genetics and pharmacogenomics in the treatment of critical illnesses. DATA
      ANALYSIS: Because most common diseases including sepsis have been shown to be
      influenced by inherited differences in our genes, completion of the Human Genome
      Project and the concomitant publication of the human single nucleotide
      polymorphism map both contribute to change our approach to medicine. Advances in
      genotyping techniques and bioinformatics enabling detection of single nucleotide
      polymorphisms have caused an explosion in pharmacogenomics-the research dealing
      with the interactions of an individual's genotype and the outcome of a drug
      therapy. Pharmacogenomics will undoubtedly be used to improve future health care
      and clinical research in different ways. Whereas treatment allocation has been
      based mainly on phenotype, genetic characterization will help researchers to
      identify suitable subjects for clinical trials, to facilitate interpretation of
      the results of clinical trials, and to identify novel targets for future drugs or
      new markets for current products. As interindividual variability in drug response
      is a substantial clinical problem, the second major objective of pharmacogenomic
      research is to decrease adverse responses to therapy through determination of
      adequate therapeutic targets and genetic polymorphisms that alter drug
      specificity and toxicity. Ultimately, genetic information will be used to select
      the most effective therapeutic agent and the optimal dosage to elicit the
      expected drug response for a given individual. Implementation of genetic criteria
      for stratification of patient populations and individual assessment of treatment
      risks and benefits emerges as a major challenge to the pharmaceutical industry.
      CONCLUSIONS: In the future, technologies such as gene chip array will enhance
      genetic medicine and provide novel insights into a patient's susceptibility to
      disease, enabling a better assessment of prognostic risk factors, quicker
      diagnosis, and accurate prediction of individual responsiveness to drugs. The
      predictable consequences of such an approach on the prevention and treatment of
      diseases could revolutionize medicine.

PMID- 12004259
TI  - Ascending aortic aneurysm and aortic root disease.

PMID- 12004260
TI  - Aortic arch aneurysms.

PMID- 12004261
TI  - Descending thoracic and thoracoabdominal aortic aneurysms.

PMID- 12004262
TI  - Thoracic aortic stent-grafts.

PMID- 12004263
TI  - Combined coronary and mitral annulus calcium detection in the non-invasive
      diagnosis of coronary artery disease in patients with systemic hypertension.
AB  - BACKGROUND: Although the presence of coronary calcium (CC) on fast spiral
      computed tomography (FSCT) is a powerful predictor of coronary artery disease
      (CAD), both the specificity and positive predictive value (PPV) of CC in CAD
      diagnosis are modest. Since previous studies have shown an association between
      mitral annular calcification (MAC) and coronary atherosclerosis, we aimed to
      investigate whether combined coronary and MAC detection could improve the non
      invasive diagnosis of CAD. DESIGN AND METHODS: Our study comprised 522 patients
      (284 men and 238 women, age ranged from 52-80 years, mean 65 +/- 6 years) who
      underwent FSCT of the coronaries as well as echo-Doppler examination. Among them,
      97 patients had prior diagnosis of prevalent proven CAD (CAD group) while 425
      patients were without clinically manifested CAD (the No CAD group). RESULTS: The
      prevalence of CC in the CAD group was 95 versus 68% in the No CAD group (P =
      0.001). The prevalence of MAC in CAD group was 63 versus 51% in No CAD group (P =
      0.03). Sensitivity and negative predictive value (NPV) of CC as a predictor of
      CAD were 95 and 96% respectively, but specificity and PPV were low: 32 and 24%
      respectively. Sensitivity and NPV of MAC as predictors of CAD were 63 and 85%
      respectively; specificity and PPV, 49 and 22% respectively. Using of combined CC
      and MAC evaluation in the prediction led to some specificity improvement at the
      expense of a similar sensitivity reduction, without a considerable gain in the
      total accuracy of the method. CONCLUSIONS: Coronary calcium detection on FSCT in
      hypertensive patients yields excellent sensitivity and NPV but relatively low
      specificity and PPV for clinically manifested CAD. Mitral annular calcification
      assessment yields a low sensitivity and specificity and its addition to CC
      evaluation does not improve non-invasive diagnosis of CAD.

PMID- 12004264
TI  - Relationship between late potentials and myocardial viability assessed by
      dobutamine echocardiography in the early postinfarction period.
AB  - BACKGROUND: In the postmyocardial infarction period, late potentials (LPs) are a
      sensitive marker for the occurrence of sustained ventricular tachycardia and
      ventricular fibrillation. The relationship between positive signal-averaged
      electrocardiogram (SAECG) and myocardial viability remains controversial. The aim
      of the present study was to assess prospectively the possible relationship
      between LPs and myocardial viability detected by dobutamine stress
      echocardiography (DSE) in the early period after myocardial infarction (AMI),
      before hospital discharge. DESIGN: Ninety-nine patients with AMI were included
      prospectively in the study. The mean age was 58 +/- 11 years, 17 were women and
      82 were men. All patients had SAEG and DSE, and 94 had coronary angiography
      before hospital discharge. RESULTS: In the overall population, presence of
      viability was demonstrated in fewer patients with LPs [37 of 70 (52%)] than
      absence of viability [18 of 29 (62%)] but the difference did not reach
      statistical significance. In the subgroup of patients with left ventricular
      ejection fraction (LVEF) lower than 40%, at higher risk of arrhythmias, the
      presence of viability was associated with the absence of LPs: 80% of the patients
      without LPs had viability by DSE (P < 0.01) and only 35% of patients with LPs had
      viability by DSE (not significant). CONCLUSIONS: In patients with an acute
      myocardial infarction and with low ejection fraction (<40%), the absence of LPs
      is related to the presence of viable myocardium as assessed by DSE early after
      the acute event. These data also suggest that myocardial viability is not the
      substrate for LPs in this population.

PMID- 12004265
TI  - Can thrombolytic therapy provide beneficial effects additional to epicardial
      coronary artery recanalization? A study based on coronary pressure measurement.
AB  - BACKGROUND: Collaterals provide significant blood supply to the myocardium at
      risk and the presence of a preserved and adequate collateral network may limit
      microvascular damage during the occlusion of an epicardial coronary artery. The
      aim of this study was to evaluate whether thrombolytic therapy (TT) may produce
      beneficial effects at the level of microvascular circulation in addition to
      epicardial coronary artery recanalization by using quantitative intracoronary
      pressure measurement techniques in patients with recent acute myocardial
      infarction (AMI). MATERIALS AND METHODS: Thirty-six patients who presented with
      AMI and had preinfarction angina pectoris, more than 60% stenosis and
      thrombolysis in myocardial infarction (TIMI) grade II flow in the infarct-related
      artery and who underwent a stent implantation procedure within 10 days of AMI
      were included in this study. Seventeen of 36 patients had received TT (group 1)
      and 19 had not received TT due to presence of contraindications or late admission
      (group 2). Quantitative coronary angiography, TIMI frame count (TFC) assessment
      and intracoronary pressure measurements were performed before and after stent
      implantation for all patients. Myocardial fractional flow reserve (FFRmyo) was
      calculated as the ratio of mean distal coronary pressure to mean aortic pressure.
      During total occlusion with balloon inflation, distal pressure was recorded as
      coronary wedge pressure (CWP). Collateral flow index (CFI) was determined by the
      ratio of simultaneously measured CWP to mean aortic pressure. RESULTS: There were
      no differences between the two groups with respect to mean per cent stenosis and
      mean FFRmyo both before and after stent implantation. The mean CWP (25.1 +/- 8.6
      mmHg compared with 17.2 +/- 6.2 mmHg, P < 0.01) and CFI (0.24 +/- 0.10 compared
      with 0.16 +/- 0.11, P < 0.01) were significantly higher and mean post-stent
      corrected TFC (18.8 +/- 3.7 compared with 22.4 +/- 3.1, P < 0.01) was
      significantly faster in the group of patients who had received TT compared to
      those who had not. CONCLUSIONS: We concluded that destruction degree of
      collateral circulation and distal microvasculature is lower in patients who had
      received TT, compared to patients who could not be treated with TT. Besides
      protective effect on collateral vessels, TT provides even more reperfusion and
      less destruction of the microvasculature.

PMID- 12004267
TI  - Involvement of Bcl-2 and IL-2R in HIV-positive patients whose CD4 cell counts
      fail to increase rapidly with highly active antiretroviral therapy.
AB  - OBJECTIVE: Combination antiretroviral therapy in a subset of HIV-infected
      patients, here called CD4-low responders (CD4-LR), fails to produce a rapid rise
      in CD4 cell counts despite effective control of plasma viral load (< 50
      copies/ml). The mechanism responsible for this failure was investigated. DESIGN
      AND METHODS: CD4-LR patients (n = 13) included in the study had been receiving
      stable antiretroviral therapy for > 9 months, resulting in undetectable viral
      load, but nontheless showed a CD4 cell count of < 200 x 106 cells/l. Samples from
      these patients were analysed for intracellular expression of the anti-apoptotic
      molecule Bcl-2 and the in vitro apoptosis of their CD4 lymphocytes. Since
      interleukin-2 (IL-2) induces Bcl-2 and participates in the control of lymphocyte
      apoptosis, we also investigated the IL-2/IL-2 receptor (IL-2R) system in these
      CD4-LR patients. All these investigations were performed before and after the CD4
      LR patients received IL-2 therapy. RESULTS: CD4 T lymphocytes from these patients
      underexpressed the anti-apoptotic molecule Bcl-2 and were more susceptible to
      spontaneous apoptosis. Peripheral CD4 T lymphocytes from the CD4-LR patients
      showed a regulatory dysfunction in the IL-2R system that resulted in a lack of
      reactivity to IL-2. Overall, the results obtained with CD4-LR patients differed
      radically from those in patients undergoing successful antiretroviral therapy.
      Finally, an increase in Bcl-2 expression and IL-2 reactivity was observed in the
      CD4 T lymphocytes of CD4-LR patients receiving IL-2 immunotherapy. This
      correlated with a reduction in their apoptosis. CONCLUSION: Our study
      characterizes the defective maintenance of peripheral CD4 T lymphocytes in CD4-LR
      patients, probably resulting from Bcl-2 underexpression and dysregulation of the
      IL-2R system.

PMID- 12004268
TI  - Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults
      treated with growth hormone.
AB  - OBJECTIVE: To determine whether treatment with growth hormone (GH) enhances
      thymopoiesis in individuals infected with HIV-1. METHODS: Five HIV-1-infected
      adults were treated with GH for 6-12 months in a prospective open-label study.
      Immunological analyses were performed before GH treatment and repeated at 3 month
      intervals after GH initiation. Thymic mass was analysed using computed tomography
      with quantitative density and volume analysis. Analysis of circulating
      lymphocytes, including naive and memory T cell subsets, was performed using
      multiparameter flow cytometry. RESULTS: GH treatment was associated with a marked
      increase in thymic mass in all GH recipients. Circulating naive CD4 T cells also
      increased significantly in all patients during GH therapy, suggesting an
      enhancement of thymopoiesis. CONCLUSION: GH has significant effects on the human
      immune system, including the reversal of thymic atrophy in HIV-1-infected adults.
      De-novo T cell production may thus be inducible in immunodeficient adults.

PMID- 12004269
TI  - HIV long-term non-progressors maintain brisk CD8 T cell responses to other viral
      antigens.
AB  - OBJECTIVE: To examine the specificity of heightened CD8 cell responses in HIV-1
      infected long-term non-progressors. DESIGN: Cross-sectional study examining CD8
      cell responses to hepatitis C virus (HCV) peptides in HCV-HIV LTNP (n = 6), HCV
      HIV progressors (n = 11), HCV singly infected patients (n = 32), HCV singly
      infected patients with self-limited disease (n = 10), HIV singly infected
      progressors (n = 7) and HCV-negative, HIV-negative controls (n = 10). METHODS:
      The frequency of HCV-reactive interferon gamma-producing cells in peripheral
      blood was assayed by enzyme linked immunospot assay using a panel of 61 HCV-1
      derived peptides. RESULTS: Five of six HCV-HIV LTNP had HCV-specific CD8
      responses. In contrast, responses were observed in 2 of 32 HCV singly infected
      patients, 2 of the 10 HCV singly infected patients with self-limited disease, and
      0 of 11 HCV-HIV progressors (P < 0.001). Both frequency of HCV-specific CD8 cells
      and number of HCV peptides recognized were greater in HCV-HIV LTNP than in other
      groups. CONCLUSIONS: HIV-infected LTNP maintain heightened CD8 cell responses to
      HCV in addition to heightened HIV specific responses. Common mechanisms may
      underlie preservation of CD8 immune responses in these individuals. An improved
      understanding of these mechanisms will help to gain insight into protective
      antiviral immunity as well as to the means whereby these viruses impair host
      defenses.

PMID- 12004270
TI  - Use of laboratory tests and clinical symptoms for identification of primary HIV
      infection.
AB  - OBJECTIVE: To determine the sensitivity and specificity of symptoms, three HIV-1
      RNA assays, a p24 antigen EIA and a third-generation enzyme immunoassay (EIA)
      antibody test for diagnosis of primary HIV infection (PHI). DESIGN: Prospective
      cohort in a university research program. PARTICIPANTS: Of 258 eligible persons
      screened for PHI, 40 had primary/early infection (22 preseroconversion, 18 within
      6 months of seroconversion) and 218 did not. Seven participants with
      preseroconversion HIV-1 from a second center were added for evaluating laboratory
      tests. MAIN OUTCOME MEASURE: PHI, defined as a negative or indeterminate antibody
      test with subsequent conversion. Symptom analysis also included persons with
      antibody conversion of less than 6 months' duration. RESULTS: The symptoms most
      strongly associated with PHI in multivariate analysis were fever [odds ratio (OR)
      5.2; 95% confidence interval (CI) 2.3-11.7] and rash (OR 4.8; 95% CI 2.4-9.8).
      The sensitivity and specificity, respectively, for detecting preseroconversion
      HIV infection were: p24 antigen, 79% and 99%; third-generation EIA, 79% and 97%;
      HIV-1 RNA by branched chain DNA 100% and 95%; HIV-1 RNA by polymerase chain
      reaction 100% and 97%; HIV-1 RNA by transcription-mediated amplification testing,
      100% and 98%. False-positive HIV-1 RNA tests were not reproducible and had values
      < 3000 copies/ml, while only one person with confirmed PHI was in this range.
      CONCLUSIONS: Rash and fever indicated the highest risk of PHI. HIV-1 RNA tests
      are very sensitive for PHI but false-positive results occur. False-positive
      results can be reduced through duplicate testing and considering tests < 5000
      copies/ml as indeterminate results requiring additional testing. p24 antigen was
      more specific than HIV-1 RNA testing but less sensitive.

PMID- 12004271
TI  - Both baseline HIV-1 drug resistance and antiretroviral drug levels are associated
      with short-term virologic responses to salvage therapy.
AB  - BACKGROUND: To determine the impact of HIV-1 drug resistance at baseline and
      antiretroviral drug levels (DL) during follow-up on virologic response to the
      next antiretroviral regimen. METHODS: Baseline genotypic and phenotypic
      susceptibility was obtained for plasma virus from patients failing a protease
      inhibitor-containing regimen. Untimed plasma antiretroviral DL were performed and
      the distribution of DL after 12 weeks of follow-up was classified as above
      (DLHigh) or below (DLLow) the median. Inhibitory quotients [IQ = (DL at week
      12)/(fold change in IC50 to wild-type)] were determined for each drug in the
      regimen. Primary outcome was change in log10 plasma HIV-1 RNA viral load
      (DeltaVL) from baseline to 12 weeks. RESULTS: There were 137 patients who had
      baseline resistance data available for the antiretroviral drugs used in the
      salvage regimen, and DL at week 12. Each drug with DLHigh was associated with
      DeltaVL = -0.40 (P = 0.0002) while each drug with DLLow had DeltaVL = -0.16 (P =
      0.11). In multivariate models DeltaVL associated with each active drug (defined
      by genotype) with DLHigh was -0.48 log10 (P < 0.0001), and with each active drug
      with DLLow was -0.22 (P = 0.03). The DeltaVL was -0.18 if no drugs in the regimen
      had an IQ > median, compared to -0.58 for one drug, -1.06 for two drugs, -0.86
      for three drugs, and -1.44 for four or five drugs with IQ > median (P < 0.0001
      for trend). CONCLUSIONS: In salvage therapy, both the number of active drugs and
      the DL for each drug in the new regimen determine the antiviral response.

PMID- 12004272
TI  - Comparative response of African HIV-1-infected individuals to highly active
      antiretroviral therapy.
AB  - OBJECTIVE: Few data exist on the virological response to antiretroviral therapy
      of individuals infected with African HIV-1 subtypes. Our objective was to compare
      the response, in our clinic, of African HIV-1-infected patients with their
      British and European contemporaries treated with the same regimes. DESIGN: The St
      Mary's Hospital HIV database was used to identify drug-naive African and European
      patients starting a highly active antiretroviral therapy (HAART) regimen.
      METHODS: HIV-1 subtype was determined by phylogenetic analysis of pol sequences.
      Kaplan-Meier survival analysis was used to estimate the proportion of patients
      achieving undetectable viral loads (< 500 copies/ml). The longer-term response to
      therapy was assessed by changes in CD4 cell counts and viral loads from baseline.
      RESULTS: A total of 265 patients were classified as 'European' and 97 as
      'African', confirmed by sequence. The time to first undetectable viral load was
      similar for the two groups (P = 0.9). Although there were no statistically
      significant differences in the CD4 cell count responses (P = 0.11), there was
      evidence of an increase in viral load after 9 months for the African group,
      resulting in a widening viral load gap between the two cohorts; the effect of
      ethnic group was statistically significant (P < 0.001). CONCLUSION: The initial
      virological and immunological responses of the African and European cohorts to
      HAART were similar; although the longer-term virological response was poorer in
      the African cohort, which may be related to adherence. On the basis of these
      findings, there is no justification for withholding HAART from Africa on
      virological grounds.

PMID- 12004273
TI  - A Phase I, placebo-controlled trial of multi-dose recombinant human interleukin
      12 in patients with HIV infection.
AB  - OBJECTIVES: Interleukin (IL)-12 is a cytokine that stimulates T lymphocytes and
      natural killer cells to generate a Type 1 T-helper lymphocyte immune response.
      The primary objective of this study was to determine the safety and immunologic
      activity of repeated recombinant human IL-12 (rhIL-12) dosing in HIV-infected
      patients over a broad range of the HIV disease spectrum. DESIGN: A randomized,
      placebo-controlled, Phase 1 trial design was chosen to control for the effects of
      HIV disease alone on safety and immunologic measurements. METHODS: HIV-infected
      patients on antiretroviral therapy received rhIL-12 or placebo twice weekly for 4
      weeks. Subjects were monitored for safety and changes in absolute lymphocyte
      subset number, serum interferon (IFN)gamma and neopterin levels, plasma HIV RNA
      level, peripheral blood mononuclear cell (PBMC)-inducible IFNgamma responses to
      mitogen, and PBMC proliferative responses to phytohemagglutinin, tetanus,
      Candida, Mycobacterium avium complex, streptokinase, and HIV p24 and gp160
      antigens. RESULTS: rhIL-12 was well tolerated at doses up to 100 ng/kg in
      subjects enrolled with CD4 cell counts < 50 x 10(6) cells/l and at all doses in
      subjects with CD4 cell counts of 300 x 10(6)-500 x 10(6) cells/l. rhIL-12
      resulted in dose-related increases in serum neopterin (particularly in subjects
      with baseline CD4 cell counts of 300-500 x 10(6) cells/l) but in no significant
      changes in other immunologic measurements or plasma HIV RNA levels. CONCLUSIONS:
      rhIL-12 dosed twice weekly at < or = 100 ng/kg was well tolerated in HIV-infected
      patients and resulted in dose-related increases in serum neopterin (possibly
      reflecting the effect of some degree of IFNgamma induction). However, there was
      no evidence of improvement in antigen-specific immune response.

PMID- 12004274
TI  - Rates of non-AIDS-defining cancers in people with HIV infection before and after
      AIDS diagnosis.
AB  - OBJECTIVE: To describe the incidence of non-AIDS-defining cancers in people with
      HIV infection before and after the occurrence of AIDS, and to examine the
      association of cancer risk with immune deficiency. DESIGN: Cohort study involving
      nation-wide linkage of HIV, AIDS and cancer registry data. METHODS: Association
      of cancer risk with immune deficiency was examined by analysing cancer risks in
      four periods between HIV diagnosis, AIDS and death. RESULTS: Linkage identified
      196 cases of non-AIDS-defining cancer in 8351 people notified with HIV infection
      and 8118 registered with AIDS (total of 13 067 individuals). Overall, we found
      significantly increased rates of cancer of the lip, anus, Hodgkin's disease,
      myeloma and leukaemia. Of these cancers, in people with HIV infection who did not
      develop AIDS, or were more than 5 years prior to development of AIDS, only cancer
      of the anus occurred at increased rates. A significant trend of increasing
      relative risk of cancer with increasing time since HIV diagnosis was found for
      Hodgkin's disease and multiple myeloma. CONCLUSIONS: People with HIV with mild
      immune deficiency prior to AIDS were at increased risk of anal cancer, but this
      may reflect other risk factors. Other cancers occurred only later in the course
      of HIV infection. This is reassuring evidence that people with HIV who are only
      mildly immune deficient may not be at increased risk of non-AIDS-defining
      cancers, but larger studies with longer periods of follow-up are needed to
      confirm this.

PMID- 12004275
TI  - High prevalence of HIV-1 subtype G and natural polymorphisms at the protease gene
      among HIV-infected immigrants in Madrid.
AB  - OBJECTIVES: Genetic characterization of HIV-1 subtypes among immigrants and
      natives infected overseas. METHODS: Phylogenetic analysis of HIV-1 protease
      sequences obtained from 109 foreigners (mainly Africans) and 32 native
      individuals infected overseas attending a reference HIV/AIDS centre located in
      Madrid, Spain. RESULTS: The overall rate of infection with HIV-1 non-B subtypes
      was 50.3% (71/141). Whereas 94.3% (67/71) belonged to immigrants (mostly
      Africans, 60/67), only 5.6% (4/71) were from native individuals (P < 0.05). The
      distribution of non-B subtypes was: 49 G, eight C, six A, four D, two F and two
      H. The high prevalence of subtype G was mainly related to individuals from west
      central Africa. Interestingly, substitutions at three or more positions
      associated with protease inhibitor (PI) resistance were recognized in 52.6% of
      naive subjects carrying non-B subtypes, but only in 8% of those infected with B
      viruses (P < 0.05). The genotypes most frequently recognized among non-B and B
      subtypes occurred, respectively, at positions 36 (100 versus 12%), 20 (77.2
      versus 0%), 63 (40.3 versus 64%), 82 (17.5 versus 0%), 10 (14 versus 12%), 77
      (3.5 versus 34%), and 71 (0 versus 2%). Accordingly, changes I-36 and I-20 may be
      considered specific genetic markers for non-B, group M variants and subtype G
      infections, respectively. CONCLUSION: Nearly two-thirds of foreigners with HIV-1
      infection in Madrid carry non-B subtypes, subtype G (protease) being the most
      common among west-central African immigrants. The high rate of natural
      polymorphisms at the protease gene in non-B viruses may compromise the response
      to PI. Therefore, HIV subtyping should be considered in treatment guidelines.

PMID- 12004276
TI  - Spare non-occupational HIV post-exposure prophylaxis by active contacting and
      testing of the source person.
AB  - OBJECTIVE: HIV-1 post-exposure prophylaxis (PEP) is frequently prescribed after
      exposure to source persons with an undetermined HIV serostatus. To reduce
      unnecessary use of PEP, we implemented a policy including active contacting of
      source persons and the availability of free, anonymous HIV testing ('PEP
      policy'). METHODS: All consultations for potential non-occupational HIV exposures
      i.e. outside the medical environment) were prospectively recorded. The impact of
      the PEP policy on PEP prescription and costs was analysed and modelled. RESULTS:
      Among 146 putative exposures, 47 involved a source person already known to be HIV
      positive and 23 had no indication for PEP. The remaining 76 exposures involved a
      source person of unknown HIV serostatus. Of 33 (43.4%) exposures for which the
      source person could be contacted and tested, PEP was avoided in 24 (72.7%),
      initiated and discontinued in seven (21.2%), and prescribed and completed in two
      (6.1%). In contrast, of 43 (56.6%) exposures for which the source person could
      not be tested, PEP was prescribed in 35 (81.4%), P < 0.001. Upon modelling, the
      PEP policy allowed a 31% reduction of cost for management of exposures to source
      persons of unknown HIV serostatus. The policy was cost-saving for HIV prevalence
      of up to 70% in the source population. The availability of all the source persons
      for testing would have reduced cost by 64%. CONCLUSION: In the management of non
      occupational HIV exposures, active contacting and free, anonymous testing of
      source persons proved feasible. This policy resulted in a decrease in
      prescription of PEP, proved to be cost-saving, and presumably helped to avoid
      unnecessary toxicity and psychological stress.

PMID- 12004277
TI  - HIV post-exposure prophylaxis: enhancing its pharmaco-economic profile by
      discriminate prescribing.

PMID- 12004278
TI  - Effects of highly active antiretroviral therapy on thymical reconstitution of CD4
      T lymphocytes in vertically HIV-infected children.
AB  - CD4 T-cell percentages, viral load and thymic function measured as T-cell
      receptor rearrangement excision circle (TREC) levels were determined every 2-3
      months in six treated HIV-infected children for 4 years. All children experienced
      a marked increase in CD4 cell count after therapy, accompanied by a concomitantly
      marked increase in TREC levels. In children, the decrease in viral load caused by
      antiviral therapy leads to an increase in CD4 T cells, mainly because of a
      recovery in the thymic production of new T cells.

PMID- 12004279
TI  - No increase in HIV incidence observed in a cohort of men who have sex with other
      men in Montreal.
AB  - To monitor HIV incidence we tested a cohort of men who have sex with men in
      Montreal for HIV every 6 months. Between 1996 and 2001, 17 out of 1244
      participants seroconverted, for an HIV incidence of 0.56 per 100 person-years
      (py) (95% CL 0.29, 0.83). The incidence decreased over the study period, from
      0.75 to 0.34 per 100 py; which was not statistically significant. An in-depth
      evaluation of the situation in Montreal could identify useful lessons for
      prevention efforts elsewhere.

PMID- 12004280
TI  - Routine HIV screening of sexually transmitted disease clinic attenders has
      favourable cost-effectiveness ratio in low HIV prevalence settings.
AB  - HIV screening for attenders of clinics for sexually transmitted disease (STD) may
      identify individuals with high-risk sexual behaviour and avert HIV infections in
      partners. Extending our previous analysis in AIDS, we performed an economic
      evaluation of HIV screening of STD-clinic attenders in Rotterdam, the
      Netherlands. The results, at euro 2987 per life-year gained, display a favourable
      economic profile. Routine HIV screening in STD clinics should be considered as a
      highly cost-effective prevention measure even in countries with a low HIV
      prevalence.

PMID- 12004281
TI  - Rapid progression of CD4 cell decline and subsequent response to salvage therapy
      in HIV-2 infection.

PMID- 12004282
TI  - Budesonide-induced acute hepatitis in an HIV-positive patient with ritonavir as a
      co-medication.

PMID- 12004283
TI  - Normalization of liver enzymes in an HIV-hepatitis C virus-co-infected patient
      after potent antiretroviral therapy.

PMID- 12004284
TI  - Gynaecomastia in HIV-infected men: association with effects of antiretroviral
      therapy.

PMID- 12004285
TI  - Survival of AIDS patients with primary central nervous system lymphoma may be
      improved by the radiosensitizing effects of highly active antiretroviral therapy.

PMID- 12004286
TI  - Intracellular carbovir triphosphate levels in patients taking abacavir once a
      day.

PMID- 12004287
TI  - Stevens-Johnson syndrome in HIV patients treated with nevirapine: two case
      reports.

PMID- 12004288
TI  - Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's
      sarcoma cells.
AB  - OBJECTIVE: To analyse if human herpesvirus 8 (HHV8)-derived viral interleukin-6
      (vIL-6) has the capacity to activate Kaposi's sarcoma (KS) cells to elicit a
      local acute-phase response. DESIGN: Proinflammatory activation of KS cells was
      compared using vIL-6, human IL-6, as well as the complex of human IL-6 with the
      soluble IL-6 receptor, and expression of the novel acute-phase protein pentraxin
      3 (PTX3) was analysed. METHODS: We established primary KS cell cultures from
      patients with AIDS-associated and classical KS and expressed recombinant HHV8
      derived vIL-6 in COS-7 cells. Expression of PTX3 by vIL-6-stimulated KS cell
      cultures was analysed by quantitative real-time reverse transcriptase-polymerase
      chain reaction. Mitogenic effects of vIL-6 on the KS cells of distinct aetiology
      were compared by [3H]thymidine incorporation. RESULTS: We show that vIL-6 induced
      a marked and sustained expression of the novel acute-phase protein PTX3 in human
      primary KS cell cultures. vIL-6 directly activated KS cells, which uniquely
      expressed gp130, the signal-transducing subunit of the IL-6 receptor, but were
      negative for the IL-6-binding unit (IL-6R). In contrast, human IL-6 did not
      stimulate KS cells in the absence of the full IL-6R. Expression of PTX3 messenger
      RNA increased by more than 25-fold in vIL-6-stimulated KS cells after 24 h.
      Particularly after extended incubation with the virokine, vIL-6 mediated a
      pronounced mitogenic effect on KS cells. CONCLUSION: The induction of an
      extrahepatic acute-phase response by vIL-6-activated KS cells may contribute to
      local tissue damage and the attraction of inflammatory cells, and add to a more
      aggressive phenotype.

PMID- 12004289
TI  - Hair follicle nevus in a distribution following Blaskho's lines.
AB  - We present a case of a rare follicular hamartoma, a hair follicle nevus. Although
      most previous reports have been solitary lesions, the case we are reporting had
      multiple papules and nodules following Blaskho's lines. There have been no
      reports of malignancies arising in these hamartomas.

PMID- 12004290
TI  - Cicatricial pemphigoid-induced phimosis.
AB  - Cicatricial pemphigoid is an autoimmune bullous disease that has a predilection
      for mucous membranes and often results in scarring. We describe a case of
      cicatricial pemphigoid with severe involvement of the glans penis, which, despite
      systemic therapy, led to phimosis.

PMID- 12004291
TI  - Multifocal disseminated lipoatrophy secondary to intravenous corticosteroid
      administration in a patient with adrenal insufficiency.
AB  - Multifocal disseminated lesions of circumscribed lipoatrophy have not been
      described as an adverse reaction of intravenously applied drugs. A unique patient
      with adrenal insufficiency is reported who received corticosteroids intravenously
      and then had multiple lesions develop that were similar to focal lipoatrophy as
      known to occur secondary to faulty intradermal injections of corticosteroids.

PMID- 12004292
TI  - Necrotic cutaneous lesions induced by hypereosinophilic syndrome secondary to a T
      cell lymphoma.
AB  - Cutaneous lesions of hypereosinophilic syndrome (HES) may display various
      presentations. These are important to recognize to allow early diagnosis. We
      report an unusual case of a young man with HES secondary to a splenic T-cell
      lymphoma, revealed by diffuse necrotic cutaneous lesions. Later on, brain and
      heart infarctions developed, leading to the patient's death. Analysis of skin
      biopsy specimens showed occluded dermal vessels surrounded by activated
      eosinophils. Because a complete analysis of hemostasis was unremarkable, these
      findings suggest that dermal vessel thrombosis was the direct consequence of the
      migration of activated eosinophils. Cutaneous lesions of HES are protean and
      probably reflect the differences between the lesional events induced in situ by
      activated eosinophils.

PMID- 12004293
TI  - Bullous adult T-cell lymphoma/leukemia and human T-cell lymphotropic virus-1
      associated myelopathy in a 60-year-old man.
AB  - Here we report a case of vesiculobullous adult T-cell lymphoma/leukemia (ATLL);
      to our knowledge the first such report of this presentation. We emphasize the
      difficulty in clinically distinguishing ATLL from cutaneous t-cell lymphoma. The
      case is further distinguished by the simultaneous presentation of human T-cell
      lymphotropic virus-1-related myelopathy in this patient, an unusual occurrence.

PMID- 12004294
TI  - Adult onset of eruptive widespread Spitz's nevi.
AB  - Cases of multiple Spitz's nevi are rare, usually occurring in the agminate form
      or even less commonly as widespread eruptive Spitz's nevi. Previously reported
      cases of widespread eruptive Spitz's nevi arose in persons age 23 or younger. We
      describe a Hispanic male patient with eruptive Spitz's nevi that presented at the
      age of 35 years.

PMID- 12004295
TI  - Vibrio vulnificus septicemia and leg ulcer.
AB  - Vibrio vulnificus is a gram-negative bacteria that can cause septicemia, wound
      infection, or a self-limiting diarrhea. This infection typically presents as an
      extremely virulent infection in patients with underlying liver disease 1 to 2
      days after exposure. We report a case of V vulnificus septicemia, cellulitis, and
      leg ulceration in a patient who had symptoms develop after exposure to brackish
      water (19 days before admission) or after ingestion of raw oysters (10 days
      before admission). The longest incubation period previously reported is 6 days.
      The diagnosis was made from identification of the bacteria from blood cultures.
      No organisms were seen or grown in culture from the skin biopsy specimen, which
      showed epidermal necrosis and dermal and subcutaneous neutrophilic abscess. We
      review 13 cases of V vulnificus septicemia and leg ulcers and their approximate
      incubation time.

PMID- 12004296
TI  - Zabon phytophotodermatitis: first case reports due to Citrus maxima.
AB  - Zabon (Citrus maxima) is a large citrus fruit belonging to the Rutaceae family
      and containing a variety of psoralens including 5-methoxypsoralen. We describe
      the first case reports of a phytophotodermatitis caused by zabon.

PMID- 12004297
TI  - Panniculitis: a cutaneous manifestation of dermatomyositis.
AB  - Specific and nonspecific panniculitis sometimes occurs during the course of
      connective tissue diseases. However, the association of panniculitis and
      dermatomyositis (DM) has only rarely been described. Previous reports have
      suggested that panniculitis may be an inherent part of DM but, because the cases
      reported are few, it is difficult to know the significance of this unusual
      association. We describe 2 patients with DM in whom panniculitis developed during
      the course of the disease, and discuss its clinical and diagnostic significance.

PMID- 12004298
TI  - Pasteurella canis osteomyelitis and cutaneous abscess after a domestic dog bite.
AB  - The genus Pasteurella is part of the normal oral flora of many animals, including
      domestic cats and dogs. In humans, Pasteurella may cause complications ranging
      from cellulitis to septicemia but rarely causes osteomyelitis or septic arthritis
      after bites and/or scratches by cats and dogs. Although Pasteurella multocida is
      a common cause of infection, other Pasteurella species have also been cultured
      from wounds in humans. We describe here, a case of a cutaneous abscess and acute
      osteomyelitis associated with P canis after a domestic dog bite. To our
      knowledge, no previous case of P canis has been reported as the cause of acute
      osteomyelitis in humans.

PMID- 12004299
TI  - HIV seronegative eosinophilic pustular folliculitis successfully treated with
      metronidazole.
AB  - We describe a patient with eosinophilic pustular folliculitis (EPF) who initially
      responded to oral indomethacin, the most often-used therapy for EPF, but
      eventually became refractory to continuous administrations. Treatment with
      metronidazole resulted in complete clearance of the lesion.

PMID- 12004300
TI  - Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome in two
      unrelated female patients.
AB  - The IFAP syndrome is characterized by the congenital onset of ichthyosis
      follicularis, absence of hair, and photophobia. A limited number of patients with
      the disorder have been described, and X-linked recessive inheritance has been
      proposed. Two unrelated female patients with a complete IFAP syndrome are
      reported. Both patients show a diffuse distribution of the disorder without
      linear arrangement. Because the suggested X-linked recessive pattern of
      inheritance is unlikely in these patients, a different way of transmission or,
      alternatively, genetic heterogeneity of the disorder has to be considered.

PMID- 12004301
TI  - Painless erythema of the hands associated with non-Hodgkin's lymphoma in a lung
      transplant recipient.
AB  - Acral erythema limited to the fingers or the hands has been described in systemic
      disease. We report the case of a 17-year-old patient who had undergone lung
      transplantation for cystic fibrosis. Six weeks after transplantation, rapidly
      growing large-cell immunoblastic non-Hodgkin's lymphoma of the lungs and
      mediastinum was diagnosed. Sharply demarcated, painless, glovelike erythema was
      found on both hands. Therapy was reduction of immunosuppression and 12 cycles of
      extracorporeal photophoresis. After 4 months, lymphoma was in clinical and
      radiologic remission. Bilateral erythema of the hands also had disappeared. Acral
      erythema has been reported in association with chemotherapy, collagen vascular
      disease, infections as with HIV, hepatitis C virus, parvovirus B19, or
      cytomegalovirus. None of the described associations were detected in this case.

PMID- 12004302
TI  - Drug-induced epidermolysis bullosa acquisita with antibodies to type VII
      collagen.
AB  - We describe a 73-year-old patient who had a subepidermal bullous eruption develop
      after a course of antibiotics, including vancomycin. The patient had deposits of
      IgA and IgG in the cutaneous basement membrane zone that were located on the
      dermal side of 1 M NaCl-treated autologous skin. By an enzyme-linked
      immunosorbent assay, the patient was found to have circulating IgG antibodies
      directed against type VII collagen, the target antigen of epidermolysis bullosa
      acquisita. Our observation expands the spectrum of immune-mediated subepidermal
      bullous skin eruptions precipitated by drugs and lends support to the idea that a
      subset of these cases represents an unusual variant of drug-triggered
      epidermolysis bullosa acquisita.

PMID- 12004303
TI  - Chronic urticaria.
AB  - Chronic urticaria has a spectrum of clinical presentations and causes. About 50%
      of patients with "idiopathic" disease have histamine-releasing autoantibodies in
      their blood. The term autoimmune urticaria is increasingly being accepted for
      this subgroup of patients, in whom immunosuppressive therapies may be appropriate
      if conventional approaches to management are unsuccessful. This article reviews
      the classification, causes, and management of chronic urticaria in light of
      recent advances in the understanding of its etiology. LEARNING OBJECTIVE: At the
      conclusion of this learning activity, participants should have up-to-date
      knowledge of the classification, assessment, and management of chronic urticaria
      and understand where the concept of autoimmune urticaria fits into existing
      frameworks.

PMID- 12004304
TI  - Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel
      cell carcinoma in sentinel lymph nodes.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNBx) can identify Merkel cell carcinoma
      (MCC) micrometastasis. OBJECTIVE: We attempted to examine the effectiveness of
      immunostaining and identify antibodies most appropriate for evaluation of SLNBxs
      for MCC. METHODS: Histopathologic material from 10 patients with MCC who had
      SLNBx was reviewed. RESULTS: Twenty-three SLNBxs from 10 patients appeared tumor
      free in routine hematoxylin-eosin (H&E)-stained sections. However, tumor cells
      were detected in immunostained sections from 5 (22%) of 23 SLNBxs in 4 (40%) of
      10 patients. Immunostains with pancytokeratin (panCK), cytokeratin-20 (CK-20),
      neurofilament protein, and chromogranin A were used for all primary and SLNBx
      specimens. All 5 (100%) micrometastatic foci stained strongly for CK-20 and
      panCK. Background normal lymph node tissue also stained for panCK but not for CK
      20. CONCLUSION: Examination of H&E sections alone is insufficient for excluding
      micrometastatic MCC in sentinel lymph nodes. We observed the greatest sensitivity
      and specificity with anti-CK-20 antibody in identifying micrometastatic MCC in
      sentinel lymph nodes.

PMID- 12004305
TI  - Laypersons' perceptual discrimination of pigmented skin lesions.
AB  - BACKGROUND: Most cutaneous malignant melanomas of the skin are visible and
      should, at least in theory, be possible to detect with the naked eye. OBJECTIVE:
      This study was conducted to learn more about laypersons' ability to discriminate
      between benign pigmented lesions and malignant ones. METHODS: Four groups of
      laypersons (n = 120) were asked to evaluate pictures of different types of
      pigmented skin lesions, before and after they received information about the ABCD
      (asymmetry, border irregularity, color variegation, and diameter greater than 6
      mm) criteria, with respect to the necessity of action. RESULTS: The respondents
      made adequate assessments of melanomas but overestimated the danger of benign
      pigmented skin lesions. Information about the ABCD criteria enhanced their
      ability to make adequate assessments. CONCLUSION: People seem to make adequate
      decisions concerning how to act if they have a melanoma. On the other hand,
      common moles and dysplastic nevi were harder to discriminate. Providing
      information to the public about the features of melanomas, in accordance with the
      ABCD criteria, might help laypersons in their perceptual discrimination of skin
      lesions.

PMID- 12004306
TI  - Management of dysplastic nevi: a survey of fellows of the American Academy of
      Dermatology.
AB  - BACKGROUND: Opinions concerning the significance of dysplastic nevi and their
      management vary among dermatologists. OBJECTIVE: The purpose of this study was to
      assess how fellows of the American Academy of Dermatology (AAD) perceive and
      manage dysplastic nevi. METHODS: Questionnaires were sent to 1216 fellows of the
      AAD; 456 questionnaires were returned. RESULTS: Almost all respondents (98%)
      accept the dysplastic nevus, or atypical mole, as an entity. Seventy-five percent
      of respondents perform follow-up total cutaneous examinations on all their
      patients with dysplastic nevi, and another 22% on some of them; 86% usually
      intend to do total removals when they perform biopsies of dysplastic nevi; 75%
      use margins of 2 mm or less when removing dysplastic nevi; 49% order baseline
      total-cutaneous photographs of some or all of their patients with multiple
      dysplastic nevi, although only 12% do so routinely; 67% prefer to re-excise
      dysplastic nevi when margins are positive, some using histologic atypia as a
      criterion; 60% recommend an ophthalmologic examination for at least some of their
      patients with many dysplastic nevi, although only 3% do so routinely; 12% always
      recommend cutaneous examinations of blood relatives of their patients with
      dysplastic nevi and another 81% recommend such examinations for at least some of
      their patients with dysplastic nevi; 23% use dermoscopy; 99% recommend self
      examination; almost 100% recommend sunscreen use and 93%, sun avoidance.
      CONCLUSION: Most respondents, in agreement with the literature, accept the
      concept that patients with dysplastic nevi are at increased risk for melanoma and
      that methods for prevention and early detection of melanomas are appropriate for
      these patients.

PMID- 12004307
TI  - The Environmental Protection Agency's National SunWise School Program: sun
      protection education in US schools (1999-2000).
AB  - BACKGROUND: Melanoma, the most fatal form of skin cancer, is rising at a rate
      faster than that of all preventable cancers except lung cancer in the United
      States. Childhood exposure to ultraviolet (UV) light increases the risk for skin
      cancer as an adult; thus starting positive sun protection habits early may be key
      to reducing incidence. METHODS: We evaluated the US Environmental Protection
      Agency's SunWise School Program, a national, environmental education program for
      sun safety of children in primary and secondary schools (kindergarten through
      eighth grade). The program was evaluated with surveys administered to
      participating students. An identical 18-question, self-administered survey was
      completed by students (median age, 10 years) in the classroom before and
      immediately after the SunWise educational program. RESULTS: Surveys were
      completed by students in 40 schools before (pretests; n = 1894) and after the
      program was presented (post-tests; n = 1815). Significant improvement was noted
      for the 3 knowledge variables: appropriate type of sunscreen to be used for
      outdoor play, highest UV Index number, and need for hats and shirts outside.
      Intentions to play in the shade increased from 73% to 78% (P <.001), with more
      modest changes in intentions to use sunscreen. Attitudes regarding healthiness of
      a tan also decreased significantly. CONCLUSIONS: Brief, standardized sun
      protection education can be efficiently interwoven into school health education
      and result in improvements in knowledge and positive intentions for sun
      protection.

PMID- 12004308
TI  - Incisional biopsy and melanoma prognosis.
AB  - BACKGROUND: There are many circumstances in clinical practice in which it is
      helpful to have a definitive diagnosis of melanoma before subjecting a patient to
      mutilating surgery. Previous studies on the effect of incisional biopsy on
      melanoma prognosis were conflicting and lacked a matched control group to account
      for the other prognostic indicators. OBJECTIVE: We set up this study to
      investigate the effect of incisional biopsy on melanoma prognosis. METHODS: The
      design was of a retrospective case control. Data were obtained from the database
      of the Scottish Melanoma Group; the database was set up in 1979 to collect
      detailed clinical, pathologic, and follow-up data on all patients diagnosed with
      melanoma in Scotland. Each incisional case was matched against 2 excision cases
      controlling for age, sex, sites, and Breslow thickness. The main outcome measures
      were time from initial biopsy to recurrence and to melanoma-related death.
      RESULTS: Two hundred sixty-five patients who had incisional biopsy before
      definitive excision of melanoma were included in the study; these were matched
      with 496 cases of excisional biopsy specimens. Cox's proportional hazard model
      for survival analysis showed that biopsy type had no significant effect on
      recurrence (P =.30) or melanoma-related death (P =.34). CONCLUSIONS: This study
      is the largest series on the effect of incisional biopsy on melanoma prognosis to
      date and the first to include matched controls. Melanoma prognosis is not
      influenced by incisional biopsy,. before definitive excision.

PMID- 12004309
TI  - Occupational allergic contact dermatitis is more prevalent than irritant contact
      dermatitis: a 5-year study.
AB  - BACKGROUND: Irritant contact dermatitis is thought to be the leading cause of
      occupational skin disease in the United States. Recent reports suggest otherwise.
      OBJECTIVES: The purposes of this study were to determine the prevalence of
      allergic and irritant forms of occupational contact dermatitis in the population
      seen at a Midwestern dermatologic referral clinic, report professions commonly
      affected by occupational skin disease, and indicate which substances are frequent
      allergens. METHODS: A retrospective analysis of patch test data collected at the
      University of Kansas between 1994 and 1999 was performed. RESULTS: Of 537
      patients who underwent patch testing, 135 (25%) had occupational skin disease.
      Allergic contact dermatitis affected 81 (60%) patients, and irritant contact
      dermatitis was found in 46 (34%). Health care professionals, machinists, and
      construction workers accounted for nearly half of all patients with occupational
      skin disease. Nickel sulfate, glutaraldehyde, and thiuram mix were the most
      common allergens. CONCLUSION: Patch tests with a wider array of allergens than
      those currently available in the United States are needed to prevent misdiagnosis
      of occupational contact dermatitis.

PMID- 12004310
TI  - Promotion of frequent tanning sessions by indoor tanning facilities: two studies.
AB  - BACKGROUND: Indoor tanning may increase the risk of melanoma and other health
      problems. Frequent users of indoor tanning facilities may be at particularly high
      risk. OBJECTIVE: In study 1 our purpose was to assess the prevalence and nature
      of indoor tanning advertisements; in study 2 we aimed to assess tanning facility
      compliance to recommended exposure schedules. METHODS: In study 1, tanning
      facility advertisements over a 4-month period from 24 San Diego County newspapers
      were monitored. In study 2, we assessed compliance with recommended exposure
      schedules via a telephone interview of 60 San Diego County tanning facilities.
      RESULTS: Approximately 75% of the indoor tanning advertisements promoted
      unlimited tanning. Only 5% of facilities were in compliance with recommended
      tanning schedules, and 100% offered "unlimited" tanning packages. CONCLUSIONS:
      These findings suggest that the indoor tanning industry, through pricing
      incentives that allow frequent sessions, may be promoting overexposure to UVR.
      Stronger legislation is needed to address this issue.

PMID- 12004311
TI  - Basal cell carcinoma in young women: an evaluation of the association of tanning
      bed use and smoking.
AB  - Basal cell carcinomas (BCCs) typically occur in middle-aged to elderly patients
      but less commonly in younger ones. In our experience, most BCCs seen in patients
      younger than 40 years are found in women. We evaluated 30 women with biopsy
      proven BCC and 30 control patients matched for sex, age, and skin type to
      determine potential risk factors for this population. Tanning bed visits, pack
      years of cigarette smoking, recreational sun exposure, number of blistering
      sunburns, and use of sunscreens were determined for both groups. Among patients
      with a BCC, the histologic type of tumor, site of involvement, method of
      treatment, follow-up period, incidence of recurrence, and presence of actinic
      keratoses were also evaluated. Patients with a BCC had a statistically greater
      number of pack years of smoking (P =.045), and a greater percentage of these
      women had experienced blistering sunburns (P =.028). Although women with a BCC
      had, on average, almost twice as many tanning salon visits (152.2 vs 83.1), this
      was not statistically significant. Sunscreen use and amount of recreational
      ultraviolet light exposure were essentially equal between the two groups. Young
      women with a BCC are more likely to have a past or current history of cigarette
      smoking and blistering sunburns. Repeated exposure to tanning beds may also be a
      contributory factor.

PMID- 12004312
TI  - Skin cancer screening by dermatologists: prevalence and barriers.
AB  - BACKGROUND: The incidence of skin cancers is increasing at an alarming rate, and
      there is currently no consensus by major health policy organizations regarding
      skin cancer screening. It has previously been shown that primary care physicians
      do not screen a majority of patients for skin cancer. OBJECTIVE: This study was
      undertaken to determine the prevalence of skin cancer screening among
      dermatologists and to detect barriers to screening. As a secondary objective, we
      set out to determine the prevalence of dermatoscopy use. METHODS: With the use of
      membership data from the 1999-2000 directory of the American Academy of
      Dermatology, a random sample of 464 American dermatologists was surveyed to
      assess their skin cancer screening practices and perceived obstacles to this
      practice. We then determined whether differences in knowledge of skin cancer
      screening recommendations, emphasis of skin cancer screening in training, or
      physician age affected the prevalence of screening. RESULTS: A total of 190
      dermatologists responded (41%). Fifty-seven respondents (30%) reported performing
      full-body skin cancer screening on all of their adult patients and 93 more (49%)
      reported screening only patients perceived to be at increased risk. Eighty
      respondents (42%) reported lack of time as an impediment to screening. Only 18
      (9%) did not screen patients because of potential patient embarrassment, whereas
      17 (9%) did not perform screening because of lack of financial reimbursement.
      Sixty-two dermatologists (33%) reported being aware of official skin cancer
      screening recommendations, but they were not more likely to screen all patients
      (P =.64) or partake in screening of all patients or only those at increased risk
      (P =.84). One hundred nineteen respondents (63%) reported that skin cancer
      screening was emphasized during their medical training and they were more likely
      to screen all patients (P =.04) or either all or high-risk patients (P =.02).
      Younger age groups of dermatologists were significantly more likely to screen all
      patients for skin cancer (P =.03). Twenty-two percent of respondents reported
      using dermatoscopy for suspicious lesions. CONCLUSION: Dermatologists report a
      high rate of screening for skin cancer despite not having knowledge of skin
      cancer screening recommendations. Inadequate time to perform full-body skin
      examinations and lack of emphasis during training were identified as possible
      barriers to this practice.

PMID- 12004313
TI  - Longitudinal study of melanocytic nevi in adolescents.
AB  - BACKGROUND: Although melanocytic nevi are the strongest known risk factors for
      melanoma, their etiology is not well understood. OBJECTIVES: This study was
      performed to assess the roles of constitutional pigmentary factors and sun
      exposure in the development of new nevi in adolescents. METHODS: A cohort of 111
      school children, aged 12 and 13 years at baseline, were followed up for 5 years.
      Whole-body counts of nevi of all sizes and detailed sun exposure histories were
      updated each year. Analyses of full-body nevus counts and of nevus counts on the
      face and neck region and on the shoulder and back region were undertaken by means
      of log-linear regression, allowing for repeated measures. RESULTS: Mean whole
      body nevus counts were 130.1 (SD = 69.9) in 1990 and 215.5 (SD = 127.1) in 1994.
      Shoulder and back counts were consistently higher than face and neck counts.
      Subjects with heavy shoulder freckling had increased nevus counts on all sites
      investigated, with a means ratio for whole-body counts of 1.11 (95% CI, 1.03
      1.19), compared with those with no freckling. Those who spent all of their school
      lunch times in the midday sun had a means ratio of 1.62 (95% CI, 1.15-2.29)
      compared with those who spent very little time in the sun during the lunch
      period. Summer holiday sun exposure was not significantly associated with
      development of nevi in this adolescent cohort. CONCLUSION: The degree of
      freckling, especially on the shoulders, and habitual midday sun exposure, rather
      than holiday sun exposure, are significant determinants of melanocytic nevi in
      Queensland adolescents.

PMID- 12004314
TI  - Elephantiasic pretibial myxedema: a novel treatment for an uncommon disorder.
AB  - Pretibial myxedema is a known manifestation of Graves' disease. Much less common
      is the elephantiasis nostras variant, which is often refractory to treatment. We
      therefore elected to try a new therapy, often used for the management of chronic
      lymphedema, called complete decongestive physiotherapy. After 6 weeks of
      intensive treatment, our patient lost 37 pounds and had reduced her edema volume
      by 47%. Her skin softened with decreased lymph seepage and she became mobile for
      the first time in years. At a 2-year follow-up visit, she exhibited sustained
      improvement. This case demonstrates that complete decongestive physiotherapy can
      provide effective, long-term control of this disease process. We suggest that
      complete decongestive physiotherapy be considered in patients with severe forms
      of pretibial myxedema, as well as those with refractory lymphedema.

PMID- 12004315
TI  - Treatment of vitiligo with the 308-nm excimer laser: a pilot study.
AB  - BACKGROUND: Present vitiligo therapies require many months of treatment and often
      result in disappointing outcomes. Common therapeutic options include phototherapy
      with psoralens plus ultraviolet A (UVA) radiation and broadband or narrowband UVB
      radiation phototherapy. Some of these modalities require regular phototherapy
      sessions several times a week for up to a year to achieve a therapeutic response.
      Targeted phototherapy with single-wavelength laser light is a treatment
      alternative that may prove to be a time-efficient and effective therapeutic
      option for the management of vitiligo. METHODS: This intervention study was
      designed as a before and after trial with a single arm. Twenty-nine patches of
      vitiligo from 18 patients (6 males and 12 females) were treated at the start of
      the study. Vitiligo patches were treated by using a 308-nm xenon-chloride excimer
      laser. Lesions were treated 3 times a week for a maximum of 12 treatments.
      Treatment was withheld if sunburn was observed and held until resolution. All
      patients had untreated vitiligo patches that served as control sites. RESULTS:
      Twenty-three vitiligo patches from 12 patients received at least 6 treatments and
      resulted in some repigmentation in 57% of the treated patches. Eleven vitiligo
      patches from 6 patients received all 12 treatments and resulted in some
      repigmentation in 82% of the treated patches. Untreated control patches remained
      unchanged. CONCLUSION: This degree of repigmentation in a period of 2 to 4 weeks
      is much higher than that achieved with any other present vitiligo therapy. The
      xenon-chloride excimer laser may represent a new treatment modality for the
      management of stable vitiligo.

PMID- 12004316
TI  - High-dose 308-nm excimer laser for the treatment of psoriasis.
AB  - BACKGROUND: The excimer laser can deliver high-intensity ultraviolet B (UVB)
      energy at 308 nm, a wavelength similar to that used in narrow-band UVB
      phototherapy. OBJECTIVE: The goal of this investigation was to evaluate the role
      of high-dose single treatments with the excimer 308-nm laser in stable plaque
      type psoriasis. METHODS: Eighteen volunteers were enrolled in the study. Two
      plaques were selected and half of each plaque was held as a control while the
      other half was treated with a single dose of either 8 or 16 times the minimal
      erythema dose. RESULTS: Sixteen subjects completed the study. Two patients signed
      up but never actually participated because of scheduling problems. Eleven showed
      significant improvement within 1 month, and 5 still demonstrated persistent areas
      of clearing at 4 months. CONCLUSION: As little as one high-dose excimer laser
      treatment can be effective for localized plaque-type psoriasis. Multiple
      treatments or other irradiation schedules with this innovative device may prove
      even more efficacious.

PMID- 12004317
TI  - The Z-plasty transposition flap for reconstruction of the middle cheek.
AB  - BACKGROUND: Large defects of the middle cheek may prove difficult to repair. Too
      wide for primary closure, such defects pose challenging reconstructive options
      because there are no cosmetic unit boundaries in which to camouflage incision
      lines without resorting to widely undermined flaps. OBJECTIVE: This article
      summarizes our experience with the Z-plasty and double Z-plasty transposition
      flaps for reconstruction of the cheek. METHODS: The Z-plasty transposition flap
      was used immediately after Mohs micrographic surgery to repair 14 defects of the
      middle cheek caused by basal cell carcinoma (n = 12) or squamous cell carcinoma
      (n = 2). In all cases, primary closure of the defect would have resulted in
      excessively long scars, scars oriented perpendicular to relaxed skin tension
      lines, and/or free-margin distortion. In 4 of these cases, a double Z-plasty was
      used. RESULTS: The cosmetic and functional outcomes were judged from good to
      excellent by patient and surgeon. No cases of infection occurred. In one patient,
      minor superficial tip necrosis healed without incident. A "spit" subcutaneous
      suture at one flap tip of another patient left a small nodular scar, which was
      primarily excised and healed well. CONCLUSIONS: The Z-plasty and double Z-plasty
      transposition flaps offer excellent primary reconstructive modalities for the
      repair of geographically isolated defects of the cheek that are large or
      misoriented for primary side-to-side closure. The theoretical and practical
      geometric characteristics of the Z-plasty transposition require preparation and
      practice to achieve consistently satisfying results.

PMID- 12004318
TI  - Coccidioidomycosis: case report and update on diagnosis and management.
AB  - Coccidioidomycosis is a disease known for its endemicity to the Southwest United
      States. However, given the current trends of more frequent tourist and business
      travel, an increasing number of coccidioidomycosis infections are being seen in
      patients in other areas of the United States. Because the majority of patients
      with disseminated disease experience cutaneous manifestations, dermatologists can
      be of primary importance in the diagnosis of this disease. We report a case of
      coccidioidomycosis manifesting as granulomatous cutaneous nodules on the face of
      an otherwise healthy white man. We attempt to provide an update on the diagnosis,
      management, and treatment of patients who present with cutaneous lesions caused
      by coccidioidomycosis infection.

PMID- 12004319
TI  - Tropical dermatology. Part II.

PMID- 12004320
TI  - Surgical pearl: removing skin-colored cosmetic tattoos with carbon dioxide
      resurfacing lasers.

PMID- 12004321
TI  - A variant of acrokeratoelastoidosis in systemic scleroderma: report of 7 cases.
AB  - We describe acrokeratoelastoidosis-like lesions on the palms of the patients with
      systemic scleroderma. Histology showed a focal hyperkeratosis with or without
      epidermal concavity, regular acanthosis, and hyalinization of collagen fibers
      and, in some cases, fragmentation and diminution of elastic fibers in the deep
      dermis. A slight degree of fibrotic change of collagen in the uninvolved
      neighboring skin was found in one case. The lesions were found in 7 of 26
      patients with systemic scleroderma who were analyzed here, and were not found in
      the unrelated connective tissue disorders (n = 32) and normal controls (n = 27).
      The cause of the unique skin lesions may be related to the altered connective
      tissue metabolism similar to that of systemic scleroderma.

PMID- 12004322
TI  - Visceral zoster as the presenting feature of disseminated herpes zoster.
AB  - Visceral dissemination of herpes zoster may follow cutaneous dissemination in
      immunocompromised patients. The skin is not necessarily the only organ affected
      and may not even be the presenting organ. Immunohistochemical stains available
      for routine paraffin-embedded tissue biopsy specimens allow for rapid diagnosis
      of varicella zoster virus. We describe a patient in whom gastric dissemination of
      herpes zoster was proven by immunohistochemistry. Unexplained hepatitis,
      pancreatitis, gastritis, or complaints of abdominal pain in immunocompromised
      patients with herpes zoster should prompt a high degree of suspicion for visceral
      zoster and immediate treatment with intravenous acyclovir.

PMID- 12004323
TI  - Cutaneous sinus histiocytosis (Rosai-Dorfman disease) presenting clinically as
      vasculitis.
AB  - The cutaneous variant of Rosai-Dorfman disease is a rare benign
      lymphoproliferative disorder that occurs without lymphadenopathy or internal
      organ involvement. We present a 55-year-old woman with a diffuse exanthematous
      eruption that evolved into pruritic papulopetechial and purpuric lesions on the
      back and lower extremities, diagnosed clinically as a vasculitis. The patient's
      lesions cleared spontaneously with no recurrence. Histopathologic examination
      showed a dense dermal nodular lymphohistiocytic infiltrate with occasional
      eosinophils, plasma cells, and neutrophils and with numerous extravasated red
      blood cells. The large, foamy histiocytes exhibited abundant pale cytoplasm,
      feathery cytoplasmic borders, and emperipolesis. A few histiocytes had
      longitudinal nuclear grooves resembling Langerhans cells; however, these cells
      were positive for S-100 protein and negative for CD1a. The clinical presentation
      of the cutaneous variant of Rosai-Dorfman disease is generally nonspecific. We
      present this case because of the unusual clinical presentation mimicking a
      vasculitis.

PMID- 12004324
TI  - Idiopathic CD4+T-cell lymphocytopenia associated with vitiligo.
AB  - The syndrome of idiopathic CD4+ T lymphocytopenia (ICTL) is defined as the
      persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells/mm(3)
      or less than 20% of the total lymphocytes in the absence of either HIV infection
      or other known causes of immunodeficiency. To date no known viral origin has been
      identified. ICTL has a variable clinical course ranging from patients with
      minimal symptoms to those who have died from opportunistic infections. We report
      a case of a 32-year-old white man with a long history of vitiligo that is
      associated with ICTL. He also had incidental psoriasis. The correlation between
      ICTL and autoimmune vitiligo suggests an aberration in the immune surveillance
      that leads to an abnormal response of CD4+ T lymphocytes in the host.

PMID- 12004325
TI  - Immediate noninvasive diagnosis of herpesvirus by confocal scanning laser
      microscopy.
AB  - In an immunocompromised host, cutaneous herpesvirus infections may be atypical
      and severe. Bedside microscopic imaging allows rapid diagnosis and prompt
      therapy. We report the case of an immunocompromised woman whose clinical
      differential diagnosis included herpesvirus infection. We used confocal scanning
      laser microscopy (CSLM) for immediate noninvasive bedside detection of histologic
      patterns diagnostic of cutaneous herpesvirus infection. We found that CLSM
      revealed the presence of pleomorphic ballooned keratinocytes and multinucleated
      giant cells in a loose aggregate of keratinocytes, inflammatory cells, and
      debris. Findings on CSLM were identical to those of conventional histologic
      examination. Prompt treatment of the immunocompromised patient produced clearing
      of cutaneous lesions. We conclude that CLSM may be a useful tool in the diagnosis
      of cutaneous herpesvirus infections.

PMID- 12004326
TI  - Anti-p200 pemphigoid: diagnosis and treatment of a case presenting as an
      inflammatory subepidermal blistering disease.
AB  - Anti-p200 pemphigoid is a recently defined subepidermal immunobullous disease. It
      is characterized by the binding of circulating IgG autoantibodies to the dermal
      side of 1 M NaCl split skin and by reactivity of these autoantibodies to a unique
      200-kd antigen on immunoblot of dermal extract. On immunoelectron microscopic
      examination, these autoantibodies deposit at the lamina lucida-lamina densa
      interface. We describe the clinical, histologic, and immunopathologic features in
      a patient with anti-p200 pemphigoid, as well as his favorable response to
      treatment with systemic glucocorticosteroids and dapsone.

PMID- 12004327
TI  - Prions in dermatology.
AB  - Prion diseases are uncommon fatal neurodegenerative disorders that have gained
      scientific importance as a result of the emergence of new forms of these diseases
      in both animals and humans. Prions appear to be composed principally or entirely
      of abnormal isoforms of a host-encoded glycoprotein. There is substantial
      scientific evidence to support the notion that bovine spongiform encephalopathy
      ("mad cow disease") has affected humans. Recent studies have demonstrated that
      prions can adhere easily to metal surfaces, and normal sterilization procedures
      are not likely to completely inactivate them. Iatrogenic transmission of prion
      diseases, such as Creutzfeldt-Jakob disease, was recognized after corneal
      transplantations, dura mater grafts, neurosurgical procedures, and the use of
      human hormones (growth hormone and gonadotropin). Although bovine collagen has
      long been recognized as a safe and biocompatible material, dermatologists should
      be aware of the theoretical potential for prion transmission when materials from
      bovine origin and products obtained from cultured cells fed with fetal or newborn
      calf serum are used.

PMID- 12004328
TI  - Controversies concerning the treatment of lice and scabies.

PMID- 12004329
TI  - Chemotherapy recall reactions.

PMID- 12004330
TI  - Herpes simplex virus-induced psoriatic flares in a patient previously treated
      with tamoxifen: a follow-up.

PMID- 12004331
TI  - CADASIL: blood test versus skin biopsy?

PMID- 12004332
TI  - UVA1 therapy for sclerodermic graft-versus-host disease of the skin.

PMID- 12004335
TI  - Bone mass in obese diabetic Zucker rats: influence of treadmill running.
AB  - Some controversy exists in the literature concerning bone mineral densitry (BMD)
      in obese, diabetic, leptin-resistant Zucker rats. To investigate this question
      further, we measured body composition and femoral bone mineral density (BMD) (by
      dual energy X-ray absorptiometry) in 10 male and 10 female 6 month-old Zucker
      rats and their homozygous lean controls. Fat mass (percent from body weight) was
      about 3 times higher in fatty rats than in lean controls. Total, diaphyseal, and
      distal metaphyseal BMD, total femoral Ca content, and femoral failure load were
      lower in Zucker rats than in controls. Moderate treadmill running (35% - 40% VO2
      max, 20-50 minutes day, 6 days/ week, for 89 days) increased BMD in these
      animals, possibly by inhibiting bone resorption, as evidenced by no change in
      plasma osteocalcin concentration but decreased urinary deoxypyridinoline
      excretion in fatty runners.

PMID- 12004336
TI  - The blood supply of the growth plate and the epiphysis: a comparative scanning
      electron microscopy and histological experimental study in growing sheep.
AB  - The blood supply of the growth plate has been described in the late 50s and early
      60s, and there was controversial discussion about the existence of transphyseal
      vessels. The vascular supply of growth plate and epiphysis of the proximal tibia
      was reinvestigated using a modern technique, the Mercox-perfusion method, in six
      sheep aged 6-24 weeks. A comparison was made among pure perfusion specimens, the
      corrosion casts, and histological sections. The metaphyseal, epiphyseal, and
      perichondral blood supply systems were confirmed. However, there was evidence of
      regular transphyseal anastomoses between the metaphyseal and epiphyseal system.
      Based on the histological arrangement of the blood vessels, the arterial blood
      flow would appear to be from the metaphysis to the epiphysis. The existence of
      transphyseal arterial vessels originating metaphyseally and seen both in cast
      preparations and histological sections was added to the present description of
      the blood supply of the growth plate. Age-related differences in the
      vascularization of the growth plate were not found in this study.

PMID- 12004337
TI  - Suppression of prostaglandin synthesis with NS-398 has different effects on
      endocortical and periosteal bone formation induced by mechanical loading.
AB  - Prostaglandins mediate adaptive bone formation induced by mechanical loading.
      Inhibition of cyclooxygenase-2 (COX-2) with NS-398 effectively blocks loading
      induced osteogenesis on the endocortical bone surface of the tibia. In this
      study, we compared the effects of selective inhibition of COX-2 with NS-398 on
      mechanically induced osteogenesis at the endocortical surface (tibia) with that
      on the periosteal surface (ulna). We further tested the effect of NS-398
      administered at different times before (3 hrs or 30 min) or after (30 min)
      mechanical loading. Mechanical loading induced lamellar bone formation on the
      endocortical surface of the tibia and the periosteal surface of the ulna. Oral
      administration of either indomethacin or NS-398 3 hrs before loading
      significantly decreased loading-induced bone formation rate (BFR) and
      mineralizing surface (MS/BS), but not mineral apposition rate (MAR), at the
      endocortical surface of the tibia and the periosteal surface of the ulna. NS-398
      reduced loading-induced MS/BS by 96% on the endocortical surface of the tibia,
      but only by 37% on the periosteal surface of the ulna (significantly different
      from endocortical, P <0.05). Indomethacin reduced MS/BS and BFR to a lesser
      extent than NS-398 and did not have different effects on the periosteal and
      endocortical surfaces. These data suggest that the endocortical bone adaptive
      response to mechanical loading is more dependent upon COX-2 activity than is the
      periosteal bone response. Intraperitoneal injection of NS-398 3 hrs before
      loading suppressed load-induced bone formation rate at the endocortical surface
      of the tibia significantly more (27%) than when administered 30 min before
      loading. When NS-398 was given 30 min after loading, bone formation was not
      significantly suppressed. These data suggest that a primary cellular mechanism of
      bone formation following brief bouts of mechanical loading involves release of
      prostaglandins from cells at the time mechanical loading is applied, rather than
      new prostaglandin synthesis associated with a mechanically induced COX-2
      expression.

PMID- 12004338
TI  - Activin A increases the bone mass of grafted bone in C3H/HeJ mice.
AB  - Activin A, a member of the TGF-b superfamily, is abundant in bone matrix, but
      little is known about its physiological role in bone metabolism. The present
      study was undertaken to determine whether topical activin A can increase the bone
      mass of isografted bone. The tibiae were bilaterally dissected from a donor
      C3H/HeJ mouse and transplanted subcutaneously in the dorsal region of a recipient
      mouse. One isografted tibia was topically infused for either 1, 2, 3, or 4 weeks
      with activin A, using an osmotic minipump at a dose of 0.02, 0.2, or 2 ng/hr. The
      other tibia was infused with 0.9% NaCl (control). The following results were
      obtained: (1) Topical activin A (2 ng/hr) stimulated periosteal bone formation
      after 2 or 3 weeks. The bone area in a standardized transverse section averaged
      1.3 fold that in the control. (2) Numerous cuboidal or conical osteoblasts
      appeared on the surface of newly formed bone after the infusion of activin A for
      2 or 3 weeks. Autoradiographic studies using 3H-proline revealed that the surface
      area of newly formed bone labelled with autoradiographic silver grains was
      greater in activin A-treated bone than in the control, suggesting an increased
      synthesis and secretion of collagen by osteoblasts. (3) Topical activin A
      increased the number of osteoclasts after 2 to 4 weeks. Furthermore, enhanced or
      increased bone resorption was observed in the projected anterior site of activin
      A-treated bone after 4 weeks. These results suggest that topical activin A
      increases the bone mass of isografted bone by increasing bone turnover.

PMID- 12004339
TI  - A role for cell-surface CSF-1 in osteoblast-mediated osteoclastogenesis.
AB  - CSF-1 is required for osteoblast-mediated osteoclast formation. Osteoblasts
      produce soluble (sCSF-1) and cell-surface forms of CSF-1 (also known as membrane
      bound CSF-1, mCSF-1) but their individual contributions to osteoclastogenesis
      remain unclear. Using glutaraldehyde-fixed primary murine osteoblasts as a source
      of mCSF-1, osteoblasts from op/op mice as a source for other osteoblast-derived
      osteoclastogenic factors and murine bone marrow as a source of osteoclast
      progenitors, osteoclast-like cells (OCL) formation was observed after 7-9 days of
      co-culture. In contrast, no OCL formation occurred when mCSF-1 expressed by
      primary murine osteoblasts was blocked by CSF-1 antibody pretreatment or when
      op/op osteoblasts were substituted for primary murine osteoblasts in the co
      culture system. Osteoclast formation was also significantly inhibited when murine
      primary osteoblasts were pretreated with an antisense phosphorothioate
      oligonucleotide against mCSF-1. Finally, mCSF-1 and sCSF-1 were synergistic in
      stimulating OCL formation. These data support the conclusion that mCSF-1 plays an
      important role in osteoblast-mediated osteoclastogenesis within the bone
      microenvironment.

PMID- 12004340
TI  - Hepatic steatosis and its relationship to transplantation.
AB  - Fatty infiltration of the liver is common in the brain-dead donor population and
      has a strong correlation with primary nonfunction after cold preservation, a
      condition that is catastrophic to liver transplant recipients. This literature
      review examines factors associated with the development, diagnosis,
      quantification, and clinical management of this difficult condition.

PMID- 12004341
TI  - Metabolic changes in the liver graft monitored continuously with microdialysis
      during liver transplantation in a pig model.
AB  - Microdialysis provides the opportunity to continuously monitor metabolic changes
      in tissue. The aim of the study is to monitor metabolic changes in the liver
      graft over time during transplantation in a pig model. Fourteen littermate female
      pigs with a body weight of 30 to 34 kg were used for seven orthotopic liver
      transplantations. Intrahepatic implantation of a microdialysis catheter into the
      liver graft was performed in the donor. Microdialysis samples were collected at
      20-minute intervals during the donor operation, cold preservation, and for 7
      hours after reperfusion in the recipient. Glucose, lactate, pyruvate, and
      glycerol concentrations were measured. After cold perfusion, glucose, lactate,
      and glycerol levels increased, whereas pyruvate levels decreased rapidly. During
      cold storage, glucose and glycerol levels increased, whereas lactate levels
      remained stable and pyruvate levels were undetectable. During implantation of the
      liver graft, glucose, lactate, and glycerol levels showed an accelerated
      increase. After portal reperfusion, glucose, lactate, and glycerol levels
      continued to increase for another 40 to 60 minutes, after which they decreased
      and finally settled at normal levels. At this time, pyruvate levels increased,
      with a peak within 2 hours after reperfusion, and then decreased to normal
      levels. Calculated lactate-pyruvate ratio increased after cold perfusion and
      remained stable during cold storage. During rewarming, it showed an accelerated
      increase, but after reperfusion, it decreased rapidly. Rewarming and reperfusion
      are most harmful to the liver, reflected by an accelerated increase in glucose
      and glycerol levels and lactate-pyruvate ratio. High intrahepatic glucose levels
      during ischemia appear to be a liver-specific event, which may represent glycogen
      degradation in injured hepatocytes.

PMID- 12004342
TI  - Effect of lamivudine treatment on survival of 309 North American patients
      awaiting liver transplantation for chronic hepatitis B.
AB  - The primary aim of this study is to determine whether treatment with lamivudine
      improved pre-liver transplantation (pre-LT) and LT-free survival of patients
      awaiting LT for hepatitis B virus (HBV)-related cirrhosis. Data from 162
      lamivudine-treated and 147 untreated transplant candidates managed at 20 North
      American transplant centers between 1996 and 1998 were collected and compared.
      Lamivudine-treated patients were more likely to be men, hepatitis B e antigen
      positive, HBV DNA positive, and have lower serum albumin levels at listing (P
      <.05). Actuarial pre-LT and LT-free survival were similar in lamivudine-treated
      and untreated patients. Using Cox regression analysis, the only significant
      predictor of pre-LT patient survival was the modified Child-Turcotte-Pugh (mCTP)
      score, whereas significant predictors of LT-free survival included ethnic
      background, lamivudine treatment, indication for LT, baseline serum alanine
      aminotransferase level, and baseline mCTP score. Lamivudine had no apparent
      effect on liver disease severity in patients undergoing LT, but appeared to
      improve disease severity in patients still awaiting LT. Breakthrough infection
      was noted in 11% of lamivudine-treated patients. We conclude that lamivudine
      therapy is not associated with improved pre-LT or LT-free survival in LT
      candidates with chronic hepatitis B. However, a subset of patients with less
      advanced liver failure may derive clinical benefit from lamivudine therapy, thus
      delaying the need for LT. In the absence of prospective, randomized, controlled
      trials of lamivudine in patients with decompensated cirrhosis, careful selection
      of patients and optimal timing of treatment are needed to balance the risk versus
      benefit of lamivudine therapy in LT candidates.

PMID- 12004343
TI  - Beneficial effect of lamivudine for hepatitis B transplant recipients.

PMID- 12004344
TI  - Pretransplantation pre-S2 and S protein heterogeneity predisposes to hepatitis B
      virus recurrence after liver transplantation.
AB  - Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection
      often is complicated by recurrence of infection despite immunoglobulin treatment.
      To evaluate whether variability in HBV genomic sequences and the target of
      antibody to hepatitis B surface antigen action in pre-LT samples may be
      associated with a high recurrence rate, HBV pre-S/S regions of 14 HBV-positive
      candidates for LT (in 9 of these patients, HBV infection subsequently recurred)
      were amplified and sequenced. Two hundred ninety-one mutations in 1,167 sequenced
      nucleotides (24.9%) were found. Of these, 120 mutations (10.2%) led to an amino
      acid change. The only significant difference between patients with and without
      recurrent disease was in the number of mutations in the pre-S2 region (total
      mutations, P =.042; missense mutations, P =.012) of pre-LT HBV DNA. In addition,
      a difference in amino-acid level was present in the pre-S2 region (P =.030). The
      delay in HBV infection recurrence was proportional to the number of pre-LT HBV
      mutations in the pre-S2 and S genes: the higher the number, the longer the
      interval between LT and recurrence of infection (pre-S2, P =.0124; S, P =.0060;
      total number of mutations in S protein, P =.0421). In conclusion, pre-LT
      determination of pre-S/S gene sequence variability showed that heterogeneity of
      the pre-S2 and, to a lesser extent, S genes was associated with a greater chance
      for HBV recurrence. Modification of B-cell epitopes of S, but especially of pre
      S2, protein leading to conformational changes and alterations in the viral
      encapsidation and secretion process may facilitate HBV recurrence and contribute
      to the failure of immune globulin therapy.

PMID- 12004345
TI  - Is it cost-effective to treat recurrent hepatitis C infection in orthotopic liver
      transplantation patients?
AB  - Hepatitis C virus (HCV) recurs in the allograft almost universally after
      orthotopic liver transplantation (OLT), with a variable course ranging from mild
      hepatitis to frank cirrhosis. The uncertain prognosis after OLT has lead to
      widely increased use of antiviral therapy in the post-OLT setting. We compared
      two scenarios (antiviral therapy versus no antiviral therapy) using a Markov
      based decision analytic model to simulate costs and health outcomes for recurrent
      HCV in three age and sex cohorts of post-OLT patients. Efficacy outcomes included
      total costs, cases of cirrhosis prevented, cases of death prevented, life-years
      gained, and cost per life-year saved. One-way sensitivity analyses were performed
      for sustained viral response; annual drug cost, discount rate, compliance,
      cirrhosis rate, decompensation rate, and cost of dying. Two-way sensitivity
      analyses were performed to compare effects of (1) changing sustained viral
      response and antiviral therapy costs, and (2) changing the sustained viral
      response and cirrhosis rate. The incremental cost-effectiveness ratio for the
      reference patient cohort of 1,000 men aged 55 years was $29,100 per life-year
      saved. The model was sensitive to drug costs, cirrhosis rate, and sustained viral
      response. The two-way sensitivity analysis showed that antiviral therapy remained
      cost-effective even if drug costs increased, as long as these increases were
      associated with higher sustained viral responses. The cost-effectiveness ratio
      also was sensitive to age and sex of cohort. The decision to treat HCV after OLT
      with antiviral therapy usually is based on many considerations. Such treatment
      can be cost-effective if baseline assumptions are met. Our model was sensitive to
      antiviral drug costs, cirrhosis rate, and sustained viral response. Patients with
      a progressive course of recurrent HCV are likely to have the greatest gain from
      antiviral therapy.

PMID- 12004346
TI  - Costimulatory blockade prevents early rejection, promotes lymphocyte apoptosis,
      and inhibits the upregulation of intragraft interleukin-6 in an orthotopic liver
      transplant model in the rat.
AB  - Costimulatory pathways have a pivotal role in the T-cell response to alloantigen.
      The role of costimulatory blockade with anti-CD154 in orthotopic liver
      transplantation (OLT) has not been examined previously. This study aims to
      investigate effects of anti-CD154 and CTLA4-immunoglobulin (Ig) in the early post
      OLT period using a major histocompatibility complex-disparate fully arterialized
      OLT model in the rat. Lewis rats underwent OLT with Dark Agouti liver allografts.
      Recipients were randomized to receive (1) isotype control, (2) anti-CD154, (3)
      CTLA4-Ig, or (4) cyclosporine A (CyA). Rats were killed day 8, and specimens were
      obtained for histological examination, terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labeling, immunohistochemistry, and
      quantitative reverse-transcriptase polymerase chain reaction. An additional five
      transplant recipients were treated with anti-CD154 for 14 days postoperatively to
      assess long-term allograft survival. All isotype control animals died on or
      before day 6 of acute rejection. Apart from four deaths caused by nonimmunologic
      causes, all treated recipients survived to day 8. The median survival of rats
      treated for 14 days with anti-CD154 was greater than 150 days. Serum aspartate
      aminotransferase and bilirubin levels normalized by day 3 in the CyA group and
      day 5 in transplant recipients treated with costimulatory blockade.
      Histologically, there was no difference between isotype controls and CTLA4-Ig
      treated animals, whereas anti-CD154-treated transplant recipients had a lower
      Banff score. CD4+ and CD8+ T-cell infiltrates were prominent in transplant
      recipients treated with costimulatory blockade. Intragraft analysis showed an
      increase in lymphocyte apoptosis, Fas ligand messenger RNA expression, and
      reduction in interleukin-6 gene expression in transplant recipients treated with
      costimulatory blockade. Costimulatory blockade did not alter intragraft gene
      expression of other mediators of T-cell priming, differentiation, and effector
      function compared with isotype control animals. In conclusion, costimulatory
      blockade prevented acute rejection, enabled long-term survival, and increased
      intragraft lymphocyte apoptosis in a high-responding rat OLT model.

PMID- 12004347
TI  - Markers of oxidative stress in cyclosporine-treated and tacrolimus-treated
      children after liver transplantation.
AB  - Oxidative stress is presumed to have a major role in cyclosporine A (CsA)- and
      tacrolimus-induced tissue toxicity. The present study was performed to elucidate
      the degree of oxidative stress after liver transplantation in CsA- and tacrolimus
      treated patients. Twenty-three patients (14 patients, CsA; 9 patients,
      tacrolimus) aged 2.5 to 18 years (mean, 9.8 years) who had undergone liver
      transplantation 1.5 to 12 years (mean, 5.4 years) before were studied. Eighteen
      healthy children aged 2 to 16.5 years (mean, 9.4 years) served as a control
      group. The following parameters were assessed: plasma lipoprotein levels; plasma
      carbonyl levels, as markers of oxidative damage to proteins; total plasma
      oxidizability, which evaluates plasma antioxidant capacity (lag phase) and
      lipoprotein susceptibility to oxidation; and plasma antioxidant capacity by
      cyclic voltammetry (CV), which measures antioxidant capacity stemming from
      hydrophilic low-molecular-weight antioxidant components. Carbonyl levels and
      rates of plasma oxidation did not differ between groups. The lag phase of plasma
      oxidation was significantly longer in CsA-treated children compared with
      tacrolimus-treated children or controls (mean, 54.4 +/- 4.8 [SE] v 40.2 +/- 2.2 v
      46.5 +/- 2.8 minutes, respectively; P < 0.05). Antioxidant capacity, assessed by
      CV, did not differ among CsA-treated patients, tacrolimus-treated patients, and
      healthy controls. Plasma alpha-tocopherol and beta-carotene levels did not differ
      between CsA-treated and tacrolimus-treated patients. In children post-liver
      transplantation, oxidative damage assessed by markers of lipid and protein
      oxidation is not increased, and plasma antioxidant capacity is not diminished.

PMID- 12004348
TI  - Evaluation of the splanchnic circulation with indocyanine green pharmacokinetics
      in liver transplant patients.
AB  - Although indocyanine green (ICG) can be used to estimate cardiac output (CO) and
      blood volume independently, a recirculatory multicompartmental ICG model enables
      description of these and additional intravascular factors. This model was used to
      describe the effect of end-stage liver disease (ESLD) on systemic and splanchnic
      hemodynamics in patients undergoing orthotopic liver transplantation. ICG
      disposition was determined during the dissection phase in six patients with ESLD
      undergoing orthotopic liver transplantation and six healthy adult living liver
      donors. After injecting ICG, plasma concentrations were obtained for
      approximately 10 to 12 minutes by noninvasive pulse dye densitometry. The
      recirculatory model characterizes three distinct intravascular circuits: lumped
      parallel fast (presumably nonsplanchnic circulation) and slow peripheral
      (splanchnic) circuits and a central circuit (central blood volume). Mean transit
      time (MTT) in the fast peripheral circuit was not different in patients with ESLD
      and controls. However, ESLD resulted in a significant decrease in MTT in the
      central (0.11 +/- 0.028 [SD] v 0.24 +/- 0.094 minutes in controls; P <.001) and
      slow peripheral circuit (0.67 +/- 0.41 v 1.37 +/- 0.37 minutes in controls; P
      <.001) because of increased flows to the central and slow peripheral circuits.
      These findings are consistent with the described hyperdynamic systemic and
      splanchnic circulations in patients with ESLD. In conclusion, the ICG model is
      able to derive estimates of not only blood volume and CO, but also splanchnic
      hemodynamics under different physiological conditions. This model can be a useful
      tool to evaluate the effect of pharmacological manipulation of splanchnic
      hemodynamics.

PMID- 12004349
TI  - Evidence of differential risk for posttransplantation malignancy based on
      pretransplantation cause in patients undergoing liver transplantation.
AB  - Organ transplant recipients are considered to be at greater risk for developing
      malignancy because of the prolonged immunosuppression associated with organ
      grafting. The purpose of this study is to determine risk factors, clinical
      characteristics, and outcomes of de novo nonlymphoid malignancies after liver
      transplantation from a large single-center series. All patients undergoing liver
      transplantation at the King's College Hospital (London, UK) between January 1988
      and December 1999 were analyzed retrospectively for the development of de novo
      malignancy in the posttransplantation period. Records were evaluated for age at
      diagnosis of malignancy, cause of liver disease, interval from transplantation to
      diagnosis of malignancy, predisposing factors for the development of cancer,
      immunosuppression regimen, treatment of malignancy, rejection episodes, and
      patient survival. Of 1,140 patients undergoing 1,271 liver transplantations, 30
      patients (2.6%) developed de novo nonlymphoid malignancy after transplantation.
      Skin cancers were the most common (n = 13), followed by oropharyngeal carcinoma
      (n = 2), bladder carcinoma (n = 2), acute leukemia (n = 2), breast carcinoma (n =
      2), and various other malignancies (n = 9). The mean time of presentation of the
      malignancy after transplantation was 45.1 +/- 32 months (range, 6 to 133 months),
      and mean age at diagnosis of malignancy was 55 years (range, 34 to 71 years). The
      incidence of de novo malignancy was significantly greater in patients who
      underwent transplantation for alcoholic liver disease compared with other groups
      (P <.001). Although the incidence of de novo nonlymphoid malignancy after liver
      transplantation is low, patients who underwent transplantation for alcoholic
      cirrhosis appear to have an increased risk for developing posttransplantation
      malignancy.

PMID- 12004350
TI  - Posttransplantation malignancies: a problem, a challenge, and an opportunity.

PMID- 12004351
TI  - Routine endoscopic retrograde cholangiography in the detection of early biliary
      complications after liver transplantation.
AB  - The value of routinely performing endoscopic retrograde cholangiography (ERC) to
      detect biliary complications in patients undergoing orthotopic liver
      transplantation (OLT) with duct-to-duct anastomosis without a T-tube is not
      known. Eighty-nine of 171 liver transplant recipients (61 men; mean age, 49.9
      years) underwent ERC 14.5 +/- 4.5 (SD) days after surgery between January 1997
      and August 1999. Findings of ERC and need for intervention for biliary
      complications were noted. ERC was successful in 71of 89 patients (80%). Nineteen
      patients (21%) required intervention for biliary complications (stricture, 13
      patients; bile leak, 6 patients). Protocol ERC detected eight of these
      complications (42%). In 4 patients, ERC failed, and 7 patients with a normal ERC
      result subsequently required intervention (2 patients in the same admission, and
      5 patients after discharge). Sensitivity, specificity, and positive and negative
      predictive values for successful ERC in detecting early biliary complications
      were 80%, 98%, 89%, and 97%, whereas those for predicting the overall rate of
      biliary complications were 53%, 98%, 89%, and 89%, respectively. Although highly
      specific and moderately sensitive in detecting early biliary complications, ERC
      performed routinely has low sensitivity in predicting the overall risk for
      biliary complications in patients undergoing OLT with unsplinted duct-to-duct
      anastomosis.

PMID- 12004352
TI  - Hepatic artery reconstruction and biliary stricture formation after living donor
      adult liver transplantation using the left lobe.
AB  - Biliary complications, including bile leak, biliary stricture, and cholangitis,
      are seen in 15% to 29% of all cases after living related liver transplantation.
      We investigate risk factors and discuss the management of biliary complications
      after living related liver transplantation in adults using left-lobe grafts. We
      studied 37 adult patients who underwent living related liver transplantation
      using left-lobe grafts. Perioperative variables were evaluated as risk factors
      for biliary strictures. The overall incidence of biliary complications was 43.2%
      (16 of 37 patients). Anastomotic strictures occurred in 8 patients, whereas bile
      leaks and cholangitis occurred in 9 and 8 patients, respectively. Anastomotic
      stricture was strongly related to a partial artery reconstruction (P <.02) and
      cholangitis (P <.01). Anastomotic biliary stricture was not associated with bile
      leak, acute cellular rejection, or infection. Our results suggest that an
      important risk factor for biliary anastomotic biliary strictures is a partial
      artery reconstruction. To minimize the risk for biliary anastomotic strictures,
      we will reconstruct both the middle and left hepatic artery.

PMID- 12004353
TI  - Tyrosinemia.

PMID- 12004355
TI  - Liposarcomas/atypical lipomatous tumors of the oral cavity: a clinicopathologic
      study of 23 cases.
AB  - Liposarcomas in the oral cavity have rarely been described, with less than 50
      reported cases to date and a purported predominance of the myxoid type. We
      reviewed our experience with 23 atypical lipomatous tumors/liposarcomas of the
      oral cavity. Twelve patients were men, 10 were women, and gender was not stated
      in one case. Age at presentation ranged from 28 to 83 years (median, 49.5 years).
      The most commonly affected site was the tongue and most cases presented as a
      slowly growing, painless mass. The clinical impression was lipoma or fibroma in
      the majority of cases. Tumor size ranged from 0.6 to 8.0 cm (median, 1.5 cm).
      Five cases were well circumscribed, 5 cases were focally infiltrative, and 13
      cases had markedly infiltrative margins. Twenty-one cases were classified as
      atypical lipomatous tumors (of which 10 showed spindle cell features), one as
      dedifferentiated liposarcoma, and one as myxoid liposarcoma. Follow-up data was
      available in 13 of the 23 cases. Five others were lost to follow-up after a short
      period. Eleven patients remained free of disease without local recurrence or
      metastasis during the period of follow-up that ranged from 10 months to 9 years
      (median, 24 months). Two patients had multiple local recurrences. Our study shows
      that atypical lipomatous tumor is the most common type of malignant fatty tumor
      to arise in the oral cavity with an apparently low risk of recurrence if widely
      excised, although follow-up is relatively limited thus far.

PMID- 12004356
TI  - Vimentin, smooth muscle actin, desmin, S-100 protein, p53, and estrogen receptor
      expression in elastofibroma and nodular fasciitis.
AB  - Elastofibroma and nodular fasciitis are two rare, benign soft tissue tumors.
      Elastofibroma is suggested to develop as a result of abnormal degeneration of
      elastic fibers after local trauma. Similarly, fibroblastic proliferation, which
      is triggered by local trauma or nonspecific inflammatory event, is suggested to
      play an important role in the origin of nodular fasciitis. In this
      immunohistochemical study, vimentin, smooth muscle actin (SMA), desmin, S-100
      protein, p53, and estrogen receptors were applied to paraffin sections of 10
      elastofibroma and four nodular fasciitis specimens to learn more about their
      histogenesis and biological behavior. All cases with nodular fibrosis were
      strongly SMA and vimentin positive, while only three weakly stained with estrogen
      receptor antibody. There was no immunreactivity for S-100, desmin, and p53 in
      nodular fasciitis. However, all elastofibroma cases were stained positively with
      vimentin. No staining was observed with SMA, S-100, desmin, and p53 in
      elastofibroma. The staining pattern of nodular fasciitis supported a
      myofibroblastic origin, whereas the SMA negativity in elastofibroma was
      correlated with fibroblastic origin.

PMID- 12004357
TI  - Primary mediastinal giant cell tumors: a clinicopathologic and
      immunohistochemical study of two cases.
AB  - Two cases of posterior mediastinal giant cell tumors are presented. The patients
      are a woman and a man, 31 and 18 years old, respectively. One of the patients had
      symptoms of paresthesias while the other was completely asymptomatic. Complete
      physical examination did not disclose evidence of tumor elsewhere. Neither
      patient had a previous history of malignancy. Surgical resection was performed.
      Histologically, both tumors were composed of a proliferation of osteoclast-like
      giant cells associated with a mononuclear cell population composed of oval and
      spindle cells. Mitotic activity and mild cellular atypia were present in the
      mononuclear cell component. No evidence of necrosis or hemorrhage could be
      demonstrated in either case. Immunohistochemically, both tumors showed strong
      positive reaction in the mononuclear component for antibodies against vimentin
      and CD68, while keratin, epithelial membrane antigen, CD45, S-100 protein, and
      desmin were negative. On clinical follow-up, both patients are alive and well
      without evidence of recurrence or metastasis 6 and 108 months after surgery. The
      present cases highlight the ubiquitous distribution of soft tissue giant cell
      tumors and the importance of considering these tumors in the differential
      diagnosis of posterior mediastinal neoplasms.

PMID- 12004358
TI  - Fine needle aspiration biopsy of the islet cell tumor of pancreas: a comparison
      between computerized axial tomography and endoscopic ultrasound-guided fine
      needle aspiration biopsy.
AB  - The objective of the present study is to compare the cytologic features of islet
      cell tumor (ICT) of pancreas obtained by endoscopic ultrasound guided fine needle
      aspiration (EUS-FNA) and computed tomography guided FNA (CT-FNA). We also
      describe the cytologic features associated with malignant ICT. Eleven cytology
      samples from 121 CT- FNA and 30 EUS- FNA of the pancreas were obtained from nine
      patients with ICT. Diff-Quik, Papanicolaou, and immunohistochemical stains to
      determine neuroendocrine differentiation and the hormonal status were evaluated.
      Cytologic features and specimen adequacy were compared between the two
      techniques. Cytologic features noted in both benign and malignant ICT were also
      compared. Nine patients (5 men, 4 women) ranging in age from 29 to 84 years (mean
      age, 53.8 years). Diagnoses consisted of benign (4) and malignant (5) ICT. EUS
      FNA was superior to CT-FNA in obtaining adequate cells (2/2 v 7/9) for the
      diagnosis and increased cellularity to perform additional immunohistochemical
      stains (2/2 v 4/7). Single, plasmacytoid cells with finely granular chromatin
      distribution characterized ICT on cytology. Mitoses (3/5) and necrosis (1/5) were
      noted in malignant ICT but not in benign ICT. EUS-FNA is superior to CT- FNA for
      obtaining cells for the diagnosis of ICT. Detection of mitoses and or necrosis
      from patients with ICT should initiate a search for metastasis.

PMID- 12004359
TI  - Acinar cystadenoma of the pancreas: a previously undescribed tumor.
AB  - A 58-year-old diabetic woman died as a result of an acute myocardial infarction
      caused by coronary atherosclerosis and thrombosis. A 9 cm multiloculated cystic
      lesion was found incidentally in the body and tail of the pancreas. The
      microcysts and locules were lined by one or two layers of normal-appearing acinar
      cells. In some locules there were clusters of acinar structures containing
      eosinophilic material. The cuboidal cells lining the locules had morphologic and
      immunohistochemical features of acinar cells. The lesion was interpreted as an
      acinar cystadenoma, the benign counterpart of the well-established acinar
      cystadenocarcinoma of the pancreas. Acinar cystadenoma should be included in the
      differential diagnosis of cystic tumors of the pancreas.

PMID- 12004360
TI  - Inflammatory pseudotumor (myofibroblastic tumor) of the heart.
AB  - Inflammatory pseudotumor (IPT) (also known as inflammatory myofibroblastic tumor)
      is an uncommon spindle cell lesion that was initially recognized in the lung and
      is now known to occur in virtually every major organ of the body. Its precise
      biological nature and clinical characteristics are still relatively uncertain. We
      report the case of a 7-month-old girl who was found to have an IPT of the right
      atrium. The rarity of IPT in the heart poses a diagnostic difficulty for both
      pediatricians and pathologists because of the clinical and morphologic overlap
      with other intracardiac masses in children. The differential diagnostic aspects
      of IPT of the heart are discussed and the literature on that lesion is reviewed.

PMID- 12004361
TI  - T-cell/periodic acid-Schiff stain: a useful tool in the evaluation of
      tubulointerstitial infiltrates as a component of renal allograft rejection.
AB  - Distinguishing between tubulitis and tubulointerstitial mononuclear cell
      infiltrates and determining the severity of tubulitis are critical components of
      diagnosing and grading renal allograft rejection using the 1993 Banff schema, the
      revised 1997 Banff schema, or the Cooperative Clinical Trials in Transplantation
      grading system. We describe a novel staining method, the T-PAS stain (CD3 and
      periodic acid-Schiff), which removes some of the subjectivity in the evaluation
      of tubulointerstitial infiltrates in renal allograft biopsies. The method simply
      combines two routine stains, immunoperoxidase staining for T cells (CD3) and
      periodic acid-Schiff (PAS) staining for tubular basement membrane, on the same
      section.

PMID- 12004362
TI  - Precursor T-cell acute lymphoblastic leukemia/lymphoma involving the uterine
      cervix, myometrium, endometrium, and appendix.
AB  - This report presents a case of precursor T-cell acute lymphoblastic
      leukemia/lymphoma (ALL) involving the uterine cervix, myometrium, endometrium,
      and appendix. The patient was a 38-year-old woman with a history of ALL who had
      been in remission for 4 years following chemotherapy. The malignant lymphoid
      infiltrate was characterized by blasts, showing scant cytoplasm, irregular
      hyperchromatic nuclei, and occasional prominent nucleoli. They were
      immunoreactive for CD45RB, CD3, CD43, CD34, and focally for TdT. Curiously, the
      blasts replaced the endometrial stroma and spared the associated epithelium. The
      patient was again treated with chemotherapy but her disease did not respond. She
      succumbed to her disease approximately 10 months after her initial evaluation for
      symptoms related to ALL relapse. Precursor T-cell ALL most commonly presents as a
      mediastinal mass in adolescent males. Although any organ may be affected,
      involvement of the female reproductive organs is rare. This case shows some of
      the varied manifestations of precursor T-cell ALL and highlights the necessity of
      considering the female reproductive tract as a possible location of relapsing
      disease.

PMID- 12004363
TI  - Plasma cell dyscrasias and the head and neck.
AB  - Structures in the head and neck (bones, soft tissues, lymph nodes, mucosa) are
      variably affected by plasma cell dyscrasias. Involvement can be manifested by
      localized lesions (extramedullary plasmacytoma or solitary plasmacytoma of bone)
      or by more diffuse disease (multiple myeloma). We present a contemporary review
      of these disorders with emphasis on patient outcomes.

PMID- 12004364
TI  - Developing the wheel.

PMID- 12004365
TI  - Quality matters.

PMID- 12004366
TI  - Employment services. Interview by Tom Keighley.

PMID- 12004367
TI  - Managing value conflicts.

PMID- 12004368
TI  - Clinical supervision. Its place within the quality agenda.

PMID- 12004369
TI  - Degrees of difficulty.

PMID- 12004370
TI  - Character. A Nightingale criterion for nursing leadership.

PMID- 12004371
TI  - Power points.

PMID- 12004372
TI  - Developing forensic nursing.

PMID- 12004373
TI  - Who's next in the queue?

PMID- 12004374
TI  - Lindsay Bates. Interview by Tom Keighley.

PMID- 12004375
TI  - Consulting the nurse.

PMID- 12004376
TI  - The wisdom of caring practice.

PMID- 12004379
TI  - Palliative care.

PMID- 12004380
TI  - The evolution of occupational health.

PMID- 12004381
TI  - Managing and leading psychiatric nursing. Part 1.

PMID- 12004382
TI  - Managing innovation.

PMID- 12004383
TI  - On the right track.

PMID- 12004384
TI  - Skills for the future. The humanity of caring.

PMID- 12004385
TI  - Motivational theories for clinical managers.

PMID- 12004387
TI  - Workplace culture determines quality of care.

PMID- 12004386
TI  - The NHS plan.

PMID- 12004388
TI  - The centre cannot hold.

PMID- 12004390
TI  - Wanted. A few good administrators.

PMID- 12004389
TI  - Disabled people as health service employees. How to break down the barriers.

PMID- 12004391
TI  - Holistic care. Is it feasible in today's health care environment? Point.

PMID- 12004392
TI  - Holistic care. Is it feasible in today's health care environment? Counterpoint.

PMID- 12004393
TI  - Succession planning. A strategy for taking charge.
AB  - This article on succession planning includes a definition of succession planning,
      the reasons for and components of succession planning, and why succession
      planning is important to the leadership of an organization, unit, division or
      department. Each component of succession planning, that is, vision, networking,
      and mentorship, is described, with examples that are intended to guide the reader
      to initiate and evaluate succession planning.

PMID- 12004394
TI  - A new direction for cognitive development in nursing to prepare the practitioners
      of the future.
AB  - The quest to improve metacognitive control of critical thinking abilities has
      gained increasing importance throughout the world during the past thirty years.
      Self-regulated learning, a concept within the construct of critical thinking, is
      currently receiving much attention from educational theorists. A self-regulated
      individual requires a dependable experiential knowledge base, uses cognitive
      critical thinking strategies in a reflective manner, and is affected by social
      and cultural influences. One purpose of this article is to review the significant
      legacy of cognitive research in nursing. The research is categorized according to
      the concepts of the self-regulation learning model; metacognitive self-regulation
      (critical thinking, information processing), behavioral self-regulation
      (reflective practice) and environmental self-regulation (social interaction,
      clinical context). Another purpose of the article is to explore some self
      regulated learning techniques that could be used to improve metacognitive control
      of critical thinking abilities in practice situations. Nursing leaders in service
      and education should consider a new approach for cognitive development in
      practice, since the result could be outcomes that are more closely aligned with
      mandates of governing bodies, growth of the discipline and patient welfare.

PMID- 12004395
TI  - Development of a nursing center using a collaborative model.

PMID- 12004396
TI  - The shift of acute care from the hospital to the home: is it a good trend? Point.

PMID- 12004397
TI  - The shift of acute care from the hospital to the home: is it a good trend? No,
      unless.... Counterpoint.

PMID- 12004398
TI  - Developing leadership and excellence with vulnerable populations in research,
      education, and practice.
AB  - The development of leadership and excellence in an area of nursing scholarship
      depends on the interactions among practice, research, theory, and education. This
      article describes the development of leadership at the UCLA School of Nursing
      through scholarship in the health-related problems of vulnerable populations.
      Leadership in scholarship began and continues in practice, influences education,
      generates theory, is tested in research, and returns to influence all of these
      areas. The vitality and creativity of scholarship and science with vulnerable
      populations depends on an ongoing infusion of knowledge from practice, research,
      theory, and education. While focusing on one school, there are many that have
      followed a similar course in developing scholarship and others that may wish to
      develop their scholarship based on this model.

PMID- 12004399
TI  - Maintaining the balance ... and thriving as a leader.
AB  - The challenges of leadership have never been greater, as health care continually
      faces unprecedented change. Today's nursing managers are confronted with demands
      from a variety of organizational stakeholders whose needs may sometimes seem
      dramatically opposite. Successful leaders of the next century will be those who
      understand these various needs and the importance of balancing them. These are
      the value-added managers who will make choices that lead to long-term success for
      their organizations, customers, employees, and leaders. They can only accomplish
      this by leading with a genuine concern for the well-being of all, defined in this
      article as love.

PMID- 12004400
TI  - Interview with Imogene King. Interview by Sandra B. Lewenson.

PMID- 12004401
TI  - Genetics counseling. A basic competency for nurses?

PMID- 12004402
TI  - Genetics counseling. Good intentions do not absolve misinformation.

PMID- 12004403
TI  - The impact of organizational climate on nurse satisfaction. Management
      implications.
AB  - The stresses and demands on nurses currently in practice and those who manage
      nursing environments are far greater than they were just a few years ago and will
      only escalate in the future. The purpose of this study was to examine the
      relationship of organizational climate dimensions on registered nurse job
      satisfaction. The sample consisted of 232 pediatric registered nurses who worked
      in all pediatric specialties. There was a statistically significant relationship
      between five climate dimensions and job satisfaction (p < .01-.001). Emphasis is
      placed on implications for nurse administrators and managers who can greatly
      impact the climate of the nursing unit and department. It is essential for nurse
      administrators and managers to plan and implement approaches that will meet the
      unique needs of their staff and institution in these particularly challenging
      times.

PMID- 12004404
TI  - Consensus and community. Achievable in American health care?

PMID- 12004405
TI  - Development of the South-East Forum on Nursing Science (SEAFONS).
AB  - The development of regional cooperation in doctoral programs in Asia is described
      along with the names of the program in each of the following countries: South
      Korea, Thailand, Japan, Hong Kong, Philippines, and Taiwan. The need for doctoral
      education in nursing is also described.

PMID- 12004406
TI  - Interview with Marilyn Jaffe-Ruiz. Interview by Sandra B. Lewenson.

PMID- 12004407
TI  - Chasing the dollars.

PMID- 12004408
TI  - New management culture in the new NHS.

PMID- 12004409
TI  - Stella Burnside. Interview by Tom Keighley.

PMID- 12004410
TI  - Effective team leadership.

PMID- 12004411
TI  - 75 per cent of GPs surveyed did not believe that they would receive good care
      when they were elderly gives pause for thought.

PMID- 12004412
TI  - Mentorship in nursing.

PMID- 12004413
TI  - Self efficacy.

PMID- 12004414
TI  - US survey finds link between patient recovery and nurse numbers.

PMID- 12004415
TI  - Why creativity lies at the heart of nursing care.

PMID- 12004416
TI  - The 5Ps of nursing management.

PMID- 12004417
TI  - Clinical governance: in acute children's services.

PMID- 12004418
TI  - Telehealth. Can nursing values be preserved.

PMID- 12004419
TI  - Telehealth. A challenge to preserve nursing values.

PMID- 12004420
TI  - Spirituality for nurses and their practice.
AB  - This descriptive study compared the inclusion of spirituality in the practice of
      two groups of nurses: nurses prepared in parish nursing (PN) and nurses not
      specifically prepared in spiritual care (NonPN). The Spirituality in Nursing Care
      tool was used to determine sources of spiritual strength and spiritual
      experiences of the respondents, the application of spirituality in their
      practice, and the interventions and indicators they used in determining the need
      for spiritual assistance. Random sampling using U.S. postal codes selected 600
      members from a national mailing list of nurses prepared in parish nursing and 600
      similarly selected nurses not prepared in parish nursing. A total of 645
      questionnaires were returned with complete data. The following question was
      asked: How do nurses prepared in providing spiritual care (PN) compare to nurses
      not similarly prepared (NonPN) in terms of: (a) personal sources of spiritual
      strength, (b) spiritual experiences, (c) application of spirituality in their
      practice, (d) identification of indicators of spiritual needs in their clients,
      and (e) interventions used to meet the spiritual needs of their clients? The
      findings indicate there are differences in how PN and NonPN groups of nurses
      respond to spirituality of self and their use of spirituality in clinical
      practice. It is suggested that parish nurses take the lead to further study
      spirituality and the indicators and appropriate interventions, and identify
      patient outcomes when spiritual needs are addressed by nurses in providing
      "holistic nursing practice."

PMID- 12004421
TI  - The 1999 Helene Fuld Health Trust Fellowship. Promoting leadership development in
      undergraduate nursing students.
AB  - In 1999, based on the recommendation of The Conservation Company. The Helene Fuld
      Health Trust selected New York University's Robert F. Wagner Graduate School of
      Public Service, in partnership with the Division of Nursing in the School of
      Education, to restructure its fellowship program for undergraduate nursing
      students. Bringing together an interdisciplinary team with experience in
      leadership development, nursing and health policy, and health care
      administration, NYU designed and delivered an innovative and state-of-the-art
      leadership development program for the 1999 Fuld Fellowship program. The new
      program started in June 1999 with 21 nursing students from all over the country.
      This article describes the goals and methods of the program; it also discusses
      early observations of the program's success that could be relevant to nursing
      education.

PMID- 12004422
TI  - Nurse managers' use of a computer decision support system. Differences in nursing
      labor costs per patient day.
AB  - To control nursing labor cost, nurse managers (NMs) need access to productivity
      indicators and financial performance information on a daily basis. Labor cost and
      hour reports after the fact are no longer acceptable for making crucial
      management/labor decisions. The purpose of this study was to determine if there
      was a mean difference in nursing labor cost per patient day (PPD) when a nurse
      manager used a labor computer decision support system (CDSS) compared to an NM
      who did not use this system. This descriptive study was implemented on a study
      and comparison unit in both a psychiatric and a medical hospital. The CDSS
      provided the NMs with daily labor cost information on which to base labor
      decisions. Study findings indicate that with the use of the labor CDSS, nurse
      managers achieved better cost performance per patient day compared to the nurse
      managers who did not use the labor CDSS.

PMID- 12004423
TI  - Creating and crossing bridges.

PMID- 12004424
TI  - Developing nursing knowledge for the 21st century.

PMID- 12004425
TI  - Developing knowledge for policy and practice for the 21st century.

PMID- 12004426
TI  - The role of the American Academy of Nursing in providing nursing leadership.

PMID- 12004427
TI  - Meeting the challenge. The role of the fellows of the Royal College of Nursing.

PMID- 12004428
TI  - Shaping health policy through nursing research and scholarship.

PMID- 12004429
TI  - Shaping health policy. The United Kingdom perspective.

PMID- 12004430
TI  - Issues of practice for the 21st century.

PMID- 12004431
TI  - Shaping nursing practice. The United Kingdom perspective.
AB  - In summary, I present these suggestions for timescale, definition, focus and key
      issues. TIMESCALE: I propose that we concentrate on the first decade of the 21st
      century, and certainly don't look beyond 2020, at least when discussing
      specifics. DEFINITION: I suggest that we agree on a working definition of our
      field of discussion--nursing practice--whether in terms of the notion of The
      Nursing Constant or an alternative construct. FOCUS: My suggestion is that we
      focus on substantive areas in need of knowledge rather than the paradigms and
      processes of knowledge building, that is, what? rather than how? KEY ISSUES: The
      key issues for 21st century nurse education and the drivers of change (Warner et
      al., 1998) are proposed (from the UK perspective) as a helpful basis from which
      to select issues for the proposed RCN/AAN collaboration on developing nursing
      knowledge for the 21st century.

PMID- 12004432
TI  - Followership in the elder care home sector.

PMID- 12004433
TI  - How to conduct an internal evaluative consultancy.

PMID- 12004434
TI  - Virtual learning.

PMID- 12004435
TI  - Planning to keep nurses in Northern Ireland.

PMID- 12004436
TI  - Helping your staff to be creative.

PMID- 12004437
TI  - Support for students.

PMID- 12004439
TI  - Good investments.

PMID- 12004438
TI  - 'Stop driving health errors underground' says healthcare managers' leader.

PMID- 12004440
TI  - [Dangerous compression dressings? Only with English dressings].

PMID- 12004441
TI  - [Quincke edema as a general practice emergency. Absolutely no tracheotomy!].

PMID- 12004442
TI  - [New therapy for painful vertebral fractures. Filling with cement instead of
      analgesics? (interview by Dr. Judith Neumaier)].

PMID- 12004443
TI  - [Threatened diabetic nephropathy. Early administration of ACE inhibitors and AT1
      blockers].

PMID- 12004444
TI  - [Every fourth first grade student is overweight. Help today your patients of
      tomorrow].

PMID- 12004445
TI  - [Therapy of chronic pancreatitis. Better results with strengthening than starving
      the patient].

PMID- 12004446
TI  - [Spirometry, pulse oximetry, brochospasmolytic test. The pillars of COPD
      diagnosis].
AB  - In addition to case history and clinical examination, the basic diagnostic work
      up of chronic obstructive pulmonary disease comprises in particular lung function
      testing by means of spirometry. In the event of an uncertain diagnosis, or in a
      search for underlying causes, an additional EKG, chest X-ray and
      bronchospasmolytic testing to determine the reversibility of the airways
      obstruction are employed. In COPD patients younger than 50, as well as in those
      with pulmonary edema largely confined to the basal fields, determination of the
      alpha-1-antitrypsin should be carried out. In the case of an exacerbation of the
      clinical presentation, the sputum should be cultured to determine the possible
      presence of pathogenic bacteria. Recurrent exacerbations or a rapid worsening of
      dyspnea necessitate hospitalization.

PMID- 12004447
TI  - [Bronchodilators--effective also in negative broncholysis test. Decreased dyspnea
      decreased in any case].
AB  - According to GOLD (Global Initiative for Chronic Obstructive Lung Disease),
      bronchodilator drugs are indicated for all degrees of severity of COPD. In stage
      1, short-acting substances are administered as required; in stage 2, permanent
      treatment with short- or long-acting bronchodilators is applied. Patients who
      fail to respond to broncholysis testing can also benefit from such treatment over
      the long term. Combination treatment with beta 2 sympathomimetics and
      anticholinergic drugs makes good sense, since additive effects can develop. Since
      COPD patients often have CAD in addition, consideration must be given to cardiac
      side effects--in particular in the case of theophylline. The sole life-prolonging
      treatment for COPD continues to be the long-term administration of oxygen; the
      only measure capable of stopping progressive deterioration of lung function is
      cessation of smoking.

PMID- 12004448
TI  - [Inhaled steroids in COPD. Do they modify the disease?].
AB  - The use of inhaled steroids in the treatment of chronic obstructive lung disease
      is controversial. It is becoming ever more clear that a differentiated approach
      to treatment determined by the clinical presentation and the specific cell
      profile is needed. More inflammation, poorer lung function and more frequent
      exacerbation benefit from steroids, while early stages of the disease with few
      symptoms, and patients with predominance of emphysema but little bronchitis are
      unlikely to benefit from this form of treatment. Particular attention must be
      paid to mixed types with an asthma-like component. While the combination of long
      acting beta-mimetic drugs and inhalative steroids might appear to be of benefit,
      the outcome of currently ongoing studies must be awaited.

PMID- 12004449
TI  - [Sleep medicine know-how for general practice. So that your patients will sleep
      well again].

PMID- 12004450
TI  - [Paroxysmal tachycardic cardiac arrhythmia. When is it life threatening?].

PMID- 12004451
TI  - [Microalbuminuria. Test for this risk factor!].

PMID- 12004452
TI  - [Hormone substitution carries risks. Painful desire for children]].

PMID- 12004453
TI  - [Current in vivo study. Comparison of the effectiveness of proton pump
      inhibitors].

PMID- 12004454
TI  - [Cost aspects. Proving possible savings first, then implementation].

PMID- 12004455
TI  - Medicare compensation would open pharmacist-managed service to more patients.

PMID- 12004456
TI  - Pharmacists work to regain public's trust after Kansas City scandal.

PMID- 12004457
TI  - Status of nation's smallpox vaccine reserve improves.

PMID- 12004458
TI  - CDC campaigns to prevent antimicrobial resistance in hospitalized adults.

PMID- 12004459
TI  - Finding more pharmacists.

PMID- 12004460
TI  - Pharmacy and Generation X.

PMID- 12004461
TI  - Protein binding of valproic acid in Japanese pediatric and adult patients with
      epilepsy.
AB  - The binding of valproic acid to serum proteins in pediatric and adult patients
      was studied. Serum samples were obtained from 48 Japanese pediatric patients with
      epilepsy (group A) and 48 Japanese adult patients with epilepsy (group B)
      receiving valproic acid monotherapy. The patients' age ranged from 1 to 15 years
      for the pediatric patients and from 18 to 44 years (group B--younger) and 45 to
      63 years (group B--older) for the adult patients. The serum concentrations of
      total and unbound valproic acid were measured by fluorescence polarization
      immunoassay, and the unbound serum fraction of valproic acid was analyzed by
      ultrafiltration. The mean association constant, K, and total concentration of
      binding sites, n(P), were as follows: group A, K = 0.016 L/mumol, n(P) = 1077
      microM; group B, K = 0.011 L/mumol, n(P) = 1365 microM; group B--younger, K =
      0.013 L/mumol, n(P) = 1291 microM; and group B--older, K = 0.006 L/mumol, n(P) =
      1827 microM. Significant differences between groups A and B were observed in the
      serum free fatty acid concentration and the serum concentration ratio of free
      fatty acids to albumin. However, no significant differences between the two
      groups were observed in the binding of valproic acid to serum proteins. Group A's
      serum concentration ratio of free fatty acids to albumin was significantly lower
      than in group B--older and was lower than in group B--younger. However, there
      were no significant differences in binding between group A and groups B--younger
      and B--older. The serum concentration of albumin was significantly higher in
      group B--younger than in group B--older. Consequently, there was a significant
      difference in binding between groups B--younger and B--older. The serum protein
      binding of valproic acid was similar in pediatric and adult patients with
      epilepsy, but binding characteristics differed between younger and older adults.

PMID- 12004462
TI  - Improving adverse-drug-reaction reporting in ambulatory care clinics at a
      Veterans Affairs hospital.
AB  - The detection of adverse drug reactions (ADRs) by a traditional passive reporting
      system and by a method involving patient and provider interviews was studied. The
      study sample consisted of randomly selected outpatients seen by their primary
      care provider during scheduled appointments in January and February 2001 at a
      Veterans Affairs medical center. After ambulatory care clinic sessions, patients
      and providers were asked (by telephone and in person, respectively) to identify
      potential ADRs. Also obtained were demographic data, information about drug
      regimens, and the severity and management of each ADR. A standardized ADR
      assessment tool was used to determine the severity of each reported reaction and
      its causal relationship with the medication. A total of 198 patients were
      included. Of these, 51 (26%) had one or more ADRs. The patient and provider
      interviews identified a total of 83 ADRs, compared with 1 ADR identified by the
      passive reporting system. When providers were made aware of the ADRs they had not
      identified, changes were made to the patient's medication regimen in 34% of
      cases. The risk of an ADR was not associated with age, number of medications, or
      provider type. Direct patient and provider interviews yielded a significantly
      higher rate of ADR detection in an ambulatory care setting than did a passive ADR
      reporting system.

PMID- 12004463
TI  - Stability of fenoldopam mesylate in two infusion solutions.
AB  - The physical and chemical stability of fenoldopam as the mesylate salt were
      studied. Test samples of fenoldopam mesylate, with fenoldopam concentrations
      ranging from 4 to 300 micrograms/mL, were prepared in polyvinyl chloride (PVC)
      bags of 5% dextrose injection and 0.9% sodium chloride injection and were stored
      at 4 degrees C in the dark and 23 degrees C in ambient fluorescent light.
      Physical and chemical stability were evaluated at 0, 24, 48, and 72 hours.
      Physical stability was assessed by visual observation in fluorescent light and
      using a high-intensity monodirectional light beam. Turbidity and particle content
      were measured electronically. Chemical stability of fenoldopam mesylate was
      evaluated by using a stability-indicating high-performance liquid chromatographic
      analytical technique. All samples were physically stable throughout the study.
      Little or no change in particulate burden and haze level was found. Little or no
      loss of fenoldopam occurred in concentrations of 40 micrograms/mL or greater at
      either temperature throughout the study period. At the lowest concentrations,
      minor losses of 3-5% were found. Fenoldopam mesylate, prepared in fenoldopam
      concentrations ranging from 4 to 300 micrograms/mL, was physically and chemically
      stable in PVC bags of 5% dextrose and 0.9% sodium chloride injections for 72
      hours when stored at 4 degrees C in the dark and 23 degrees C when exposed to
      ambient fluorescent light.

PMID- 12004464
TI  - Diabetes self-care knowledge among outpatients at a Veterans Affairs medical
      center.

PMID- 12004465
TI  - Visual compatibility of azithromycin with 24 commonly used drugs during simulated
      Y-site delivery.

PMID- 12004466
TI  - Assessing unit dose system discrepancies.

PMID- 12004467
TI  - Development and evaluation of a medication education videotape for hospitalized
      patients.

PMID- 12004468
TI  - Clinical training program based on a practice change model.

PMID- 12004469
TI  - Justifying a multidisciplinary high-intensity hepatitis C clinic by using
      decision analysis.

PMID- 12004470
TI  - Implementation of the first pharmacist-managed ambulatory care anticoagulation
      clinic in South Korea.

PMID- 12004472
TI  - Hepatitis C pharmacotherapy clinic.

PMID- 12004471
TI  - International Normalized Ratio fluctuation with warfarin-fluorouracil therapy.

PMID- 12004473
TI  - Medication naming, labeling, and packaging.

PMID- 12004474
TI  - Medication naming, labeling, and packaging.

PMID- 12004475
TI  - Medication naming, labeling, and packaging.

PMID- 12004476
TI  - Medication naming, labeling, and packaging.

PMID- 12004477
TI  - Medication naming, labeling, and packaging.

PMID- 12004478
TI  - Predicting in-home time of community care professionals.
AB  - The aim of this study was to test whether the client homebound score (CHS), the
      case management intensity score (CMIS) and the client priority visit score (CPVS)
      could be used to predict in-home time of professional caregivers in the Aspen
      community care program. A random sample of 34 community care clients from the
      different geographical areas of the Aspen Regional Health Authority was selected
      and the home visits for each client were tracked for three months. Information
      such as client demographics, the client diagnostic category, number and in-home
      time of visits was collected. In addition, the CHS, the CMIS and the CPVS were
      measured for each client. Data were analyzed, using a robust variance estimator
      regression model. CMIS was found to be the best predictor of in-home time
      (coefficient 9.521, p > 0.001), followed by the CHS and the CPVS.

PMID- 12004479
TI  - A mens' meeting place: quality and service effectiveness.
AB  - An audit on quality and service effectiveness at a community mens' meeting place
      located in Kwinana, Western Australia, was undertaken using the tools for
      reviewing mental health services, in accordance with the 1997 National Standards
      for Mental Health Services. A psychologist collected data, throughout a six-week
      period, using client and chart assessment. A total of 36 consumers, four
      counsellors and the coordinator were interviewed, both formally and informally.
      The questions asked reflected the specific criteria related to each standard.
      Following a review of the results a detailed follow-up and feedback plan was
      developed, with the suggestion to implement and review organisation specific
      policies and practices using the 360-degree cycle of monitoring, assessing,
      taking action, follow-up and feedback.

PMID- 12004480
TI  - Marketing issues for the hospital industry.
AB  - The controls on payments by insurance companies and governmental agencies
      (Medicare, Medicaid, Title 19) to hospitals have led to restricted hospital
      services for patients. This situation has caused over-capacity in hospitals.
      Also, there is a surplus of both hospital capacity and doctors. However, there
      are frequent shortages of nurses and many other trained technical personnel. This
      situation has behavioral implications which are discussed in this paper.

PMID- 12004481
TI  - The Connecticut Mental Health Center Patient Profile Project: application of a
      service needs index.
AB  - This article describes a quality assurance effort aimed at defining the
      characteristics of the patient population of the Connecticut Mental Health
      Center, a statefunded agency that provides comprehensive clinical and
      rehabilitative services to persons with mental illness. Also described is how
      this information guided management decisions in both caseload distribution and
      clinical service development. This "Patient Profile Project" was informed by
      research principles which view evaluation as continual, rather than terminal
      activity that involves key stakeholders from all levels within the mental health
      system of care and makes maximum use of data in ongoing performance improvement
      initiatives. The service-need index that the project produced represents our
      first efforts to accurately capture service need and use it in clinical decision
      making. This review of the Connecticut Mental Health Center Patient Profile
      Project illustrates the utility of a continuous evaluation system in promoting
      improvements in a large mental health treatment system.

PMID- 12004482
TI  - The nature and value of accreditation in the UK.

PMID- 12004483
TI  - The "doctor-customer" relationship: Hippocrates in the modern marketplace.
AB  - We performed a consecutive survey of 100 people presenting to a hospital injury
      clinic to ascertain their attitude to terminology currently used to describe them
      in our own institution and in the international literature. The results of this
      demonstrated that the subjects significantly preferred the traditional
      assignation "patient" rather than terms such as client or customer. This finding
      reflects the need to remember peoples' attitudes and expectations from their
      consultation with their doctor. Although business models undoubtedly help in the
      provision of an efficient health care service, remaining at the centre of this
      encounter is a doctor-patient relationship that involves a more complex
      interaction than simply a market transaction.

PMID- 12004484
TI  - Clinical Practice Guidelines for borderline personality disorder.

PMID- 12004485
TI  - Development of the American Psychiatric Association Practice Guideline for the
      Treatment of Borderline Personality Disorder.

PMID- 12004486
TI  - Practice guideline for the treatment of borderline personality disorder: a bridge
      too far.

PMID- 12004487
TI  - The borderline personality disorder practice guidelines: the good, the bad, and
      the realistic.

PMID- 12004488
TI  - A critique of the American psychiatric practice guideline for the treatment of
      patients with borderline personality disorder.

PMID- 12004489
TI  - Commentary on the American Psychiatric Association guidelines for the treatment
      of borderline personality disorder: evidence-based psychiatry and the quality of
      evidence.

PMID- 12004490
TI  - Dimensional personality profiles of borderline personality disorder in comparison
      with other personality disorders and healthy controls.
AB  - The present study examined the sensitivity and clinical specificity of
      dimensional personality profiles associated with borderline personality disorder
      (BPD) by comparing three groups of patients: (a) patients with BPD according to
      DSM-IV criteria (n = 31); (b) patients with other DSM-IV PD (n = 31); and (c)
      general population controls (n = 31). All three samples were matched for age and
      gender and the two patient samples were matched for chronicity and depressive
      symptoms. All patients were given the Six-Factor Test measuring the five-factor
      model of personality (FFM), the Temperament and Character Inventory (TCI), and
      the Dimensional Assessment of Personality Pathology (DAPP). Nonparametric
      statistics were applied to analyze the data (Mann-Whitney-U-tests for group
      comparisons; Spearman's coefficients for correlational analyses). Neuroticism
      (FFM), Self-Directedness (TCI), and Emotional Dysregulation (DAPP) were
      identified as general markers of personality pathology, which were significantly
      interrelated in all three samples. BPD patients also showed a specific profile
      compared with other PD patients with lower scores on Agreeableness (FFM), higher
      scores on Novelty Seeking and Self-Transcendence (TCI), and higher scores on the
      DAPP higher-order dimensions of Emotional Dysregulation, Dissocial Behavior, and
      Inhibitedness. Results support the assumption that BPD can be characterized by
      dimensional approaches with sufficient sensitivity in comparison with healthy
      controls and specificity in comparison with other PD patients.

PMID- 12004491
TI  - Attachment, parental bonding and borderline personality disorder features in
      young adults.
AB  - The relations between parental bonding and attachment constructs and borderline
      personality disorder features were examined in a sample of 393 18-year-old
      participants. Hierarchical regression analyses revealed that parental bonding and
      attachment scores (especially insecure attachment, anxious or ambivalent
      attachment, and a perception of a relative lack of caring from one's mother) were
      uniquely associated with borderline features beyond what could be accounted for
      by gender, childhood adversity experiences, Axis I disorder, and nonborderline
      Axis II symptoms. Although relatively modest, these relations suggest that
      bonding and attachment constructs might be considered in comprehensive
      etiological models of borderline personality disorder.

PMID- 12004492
TI  - Health service use costs by personality disorder following specialist and
      nonspecialist treatment: a comparative study.
AB  - The impact of specialist psychosocial treatment on health service use costs by
      patients with personality disorder is not yet sufficiently documented. In this
      prospective study we compare patterns of health service costs by three groups of
      people with personality disorder treated in a hospital-based program (IPP), a
      step down program (SDP), and a general psychiatric program (GPP). Total service
      use costs at follow up, compared with intake costs, showed that significantly
      higher savings were achieved by SDP and IIP compared with GPP. Cost reductions in
      SDP were significantly greater than in IPP. Significant cost reductions were
      found between treatment programs in social worker and community psychiatric
      nursing and psychotherapy. The cost-effectiveness of the two specialist treatment
      programs was indicated by the significant association between total cost
      reduction and clinical outcome in GPP and IPP, but not in GPP. The effect of
      Major Depression and Borderline Personality Disorder on health service use alone
      and in combination was also investigated. The finding that Major Depression was
      found to be more significantly associated with higher health service use costs
      than Borderline Personality Disorder is discussed.

PMID- 12004493
TI  - Personality and mood correlates of avoidant personality disorder.
AB  - Avoidant personality disorder (APD) has been recognized as prevalent and
      clinically important; however, it is not clear how APD maps onto established
      personality and mood dimensions. In this cross-sectional survey study, 365
      college students completed questionnaires assessing APD features and
      theoretically relevant personality and mood dimensions. Based on these self
      report data, 6.6% may meet DSM-IV criteria for APD. Hierarchical regression
      analyses showed that APD features were associated with introversion, neuroticism,
      low self-esteem, and pessimistic expectancies. Additionally, APD features were
      linked with self-reports of elevated emotional responsiveness to threats and
      reduced emotional responsiveness to incentives (the behavioral inhibition system
      and behavioral activation system scales). After controlling for the effects of
      other personality, temperament, and cognitive measures, affective distress (i.e.,
      anger, anxiety, and depression) was no longer related to APD. Results are
      consistent with APD models that emphasize the joint influences of emotional
      vulnerability and social-cognitive triggering and sustaining factors.

PMID- 12004494
TI  - Borderline personality disorder and age of onset in major depression.
AB  - In the present report from the Rhode Island Methods to Improve Diagnostic
      Assessment and Services (MIDAS) project, we tested the hypothesis that borderline
      personality disorder (BPD) accounts for the observed differences between early
      and late onset major depressive disorder (MDD). A total of 440 depressed
      outpatients were evaluated with semistructured interviews. Patients were
      subdivided by age of onset and the presence or absence of comorbid BPD. The
      overall pattern of clinical and demographic variables differed and two separate,
      multiple, logistic regression analyses addressed the association between age of
      onset and BPD in MDD patients. Comorbid BPD was not significant in the
      multivariable age of onset equation and the results of the multivariable analyses
      support the idea of difference between subtypes. It is concluded that although
      early age of onset is predictive of BPD, BPD is not a universal feature of early
      onset MDD.

PMID- 12004495
TI  - NHS activity. Running out of juice.
AB  - Productivity, as traditionally measured in the NHS, may have levelled off. The
      Department of Health has acknowledged productivity problems. Current measurement
      indicators do not take account of quality, so improvement to services may show up
      as decreases in efficiency. Quality improvements should be included in
      productivity measurement.

PMID- 12004496
TI  - Ward staffing. Safety in numbers.
AB  - A model for reviewing ward staffing and quality of care in a district general
      hospital has led to extra nurses being appointed. The review found correlation
      between low staffing and a high number of clinical incidents. The results have
      led to changes in practice and action to tackle sickness absence.

PMID- 12004497
TI  - US healthcare. Battle fatigue.

PMID- 12004498
TI  - First person. Bright sparks.

PMID- 12004499
TI  - Data briefing. Information for patients.

PMID- 12004500
TI  - On the budget overview. Riches beyond compare.

PMID- 12004501
TI  - On the budget analysis. Start counting.

PMID- 12004502
TI  - On the budget analysis. Realism needed on timescales.

PMID- 12004503
TI  - On the budget analysis. Bridging the divide.

PMID- 12004504
TI  - A question of style?

PMID- 12004505
TI  - Performance appraisal.

PMID- 12004506
TI  - How to conduct a feasibility consultancy.

PMID- 12004508
TI  - Prison health care.

PMID- 12004507
TI  - Stress detector.

PMID- 12004509
TI  - The rise of the specialist nurse.

PMID- 12004510
TI  - Modernisation: nursing's opportunity?

PMID- 12004511
TI  - A new broom. The Care Standards Act.

PMID- 12004512
TI  - One year on.

PMID- 12004513
TI  - Transfer deals.

PMID- 12004514
TI  - Shared benefits of funding research.

PMID- 12004515
TI  - Social support.

PMID- 12004516
TI  - Cost benefit analysis.

PMID- 12004517
TI  - Mapping the service environment.

PMID- 12004518
TI  - Nurses and teachers top the stress tables.

PMID- 12004519
TI  - Health service joins agriculture and construction as high risk work environment.

PMID- 12004520
TI  - Changing culture and deprofessionalisation.

PMID- 12004521
TI  - Evaluating on-line continuing education for nurses.
AB  - The rapid increase in web sites for nursing continuing education demands critical
      appraisal by the user. The level of anonymity of the web site authors and
      sponsors may lead to a laxity of accountability found in no other media. This
      article discusses criteria for web site evaluation and provides a rating
      instrument to assist learners in determining the quality and usability of an on
      line nursing continuing education offering. Using the rating instrument, two web
      sites are reviewed. A list of selected nursing continuing education web sites is
      included.

PMID- 12004522
TI  - Reflections on achieving professional leadership.
AB  - This inspirational message was prepared as the capstone speech for the 1999
      Helene Fuld Health Trust Fellowship Program for Emerging Nurse Leaders. At the
      time Dr. Fitzpatrick was President of the American Academy of Nursing. Key to her
      message is that future leaders should be encouraged to focus on the development
      of a career perspective as they develop transformational leadership skills.

PMID- 12004523
TI  - Interview with Joan Lynaugh [interview by Sandra B. Lewenson].

PMID- 12004524
TI  - Primary and secondary prevention. Are nurses making a substantial contribution?

PMID- 12004525
TI  - Primary and secondary prevention. Isn't primary health care synonymous with
      nursing practice?

PMID- 12004526
TI  - Where will I go? Displaced nurses relate their experiences.
AB  - Registered nurses have been experiencing displacement, the nonvoluntary transfer
      or reassignment of the registered nurse to another unit or position, or layoff,
      termination, and severing of nursing personnel as a result of the closure of
      hospitals and other agencies and the physical relocation of departments or units.
      The purpose of this qualitative study is to describe the human experience of
      change from the perspective of displaced nurses. Thirteen registered nurses
      employed at eight metropolitan New York agencies described their experiences of
      displacement. Their interviews were analyzed using grounded theory methodology.
      Five themes emerged in the displacement experience: finding out, weighing
      options, coping with negative emotions and loss, support, and giving advice.
      Implications for education, practice, and research are discussed.

PMID- 12004527
TI  - Developing a fair use of resources.

PMID- 12004528
TI  - Speak out loud for nursing.

PMID- 12004529
TI  - Demystifying supervision.

PMID- 12004530
TI  - Innovate and prosper.

PMID- 12004531
TI  - Clinical leadership that works.

PMID- 12004532
TI  - Conducting a process consultancy.

PMID- 12004533
TI  - Mapping the environment--Part 2.

PMID- 12004534
TI  - Massive increase in reported violence against NHS staff.

PMID- 12004535
TI  - Scottish solutions.

PMID- 12004536
TI  - NHS Plan Wales.

PMID- 12004537
TI  - Lymphatic filariasis.

PMID- 12004538
TI  - Take another look: proposed changes to privacy rule.

PMID- 12004539
TI  - 10 ways to keep implementation costs under control.

PMID- 12004540
TI  - Is the FCA effectively fighting healthcare fraud?

PMID- 12004542
TI  - Too much information: fighting against genetic discrimination.

PMID- 12004543
TI  - E-health: what's outside the privacy rule's jurisdiction?

PMID- 12004544
TI  - A chief privacy officer's day: the passion and pressure to succeed.

PMID- 12004545
TI  - A patient-friendly approach to the record amendment process.

PMID- 12004547
TI  - H&P requirements become more uniform.

PMID- 12004548
TI  - Six Sigma makes sense as quality initiative.

PMID- 12004549
TI  - Get serious about paper record destruction.

PMID- 12004550
TI  - ICD-9 raises concerns for home health information managers.

PMID- 12004551
TI  - Coding worldwide: gain a global perspective with IFHRO (International Federation
      of Health Records Organizations).

PMID- 12004552
TI  - Infection-control basics. A common sense review for EMS personnel.
AB  - Infection-control principles and practices based on science and common sense have
      been around for thousands of years. They've proven effective. If you know how a
      disease is transmitted, then you'll know what PPE to use to block transmission.
      Viruses don't multiply or survive for long outside a living host, so they may be
      present on a given surface, but in low numbers--and most often not numbers large
      enough to cause infection. However, hepatitis B virus can survive up to seven
      days in the presence of dried blood; that's why contaminated equipment must be
      cleaned as soon as possible after use. If it's not possible to use PPE in a given
      situation or it fails, then post-exposure medical follow-up and treatment can
      protect you. Ensuring there's an effective communication network in place for
      reporting an exposure to your DO is essential. Your agency should verify that
      hospitals are aware of their responsibilities under the Ryan White Law to share
      patient testing information if an exposure event occurs. The DO's role includes
      working with hospitals to provide proper medical follow-up, rapid patient testing
      and counseling for the exposed provider. Your DO is your advocate. Each and every
      component of your department's exposure control plan assists in reducing the risk
      for acquiring an infection on the job. Risk reduction and risk management are
      both vital. Ultimately, the responsibility lies with you--the provider--to know
      infection-control principles and practice good habits.

PMID- 12004553
TI  - Diffuse axonal injury. The mysterious & delicate nature of our fragile brain.

PMID- 12004554
TI  - Adios, Rampart: give medical control the boot.

PMID- 12004555
TI  - If patients came with instructions.

PMID- 12004556
TI  - After the smoke clears. Understanding GSW forensics & the importance of evidence
      preservation.

PMID- 12004557
TI  - Triangle of death. How hypothermia acidosis & coagulopathy can adversely impact
      trauma patients.

PMID- 12004558
TI  - Prehospital incident profiles. Gone fishin.

PMID- 12004559
TI  - Prehospital incident profiles. ATV vs. tree. More than blunt trauma.

PMID- 12004560
TI  - Young recruits. Innovative EMT program brings high school students into local EMS
      system.

PMID- 12004562
TI  - Women and cardiac rehabilitation after heart surgery: patterns of referral and
      adherence.
AB  - This cross-sectional, descriptive study examined patterns of referral of women to
      cardiac rehabilitation programs after heart surgery, their adherence to those
      programs, and whether their participation differed according to their age ranges.
      A Cardiac Rehabilitation Participation questionnaire was mailed to 157 women who
      were selected from the records of 4 hospitals and 7 physician groups. Of the 157
      women, 122 had been referred to a cardiac rehabilitation program. Ten (8.3%) of
      122 did not attend the program at all, and 25 (29%) did not attend as often as
      had been recommended. Women who had bypass surgery were more likely to have been
      referred than were those who had valvular surgery. Patterns of referral and
      adherence were similar in older women (66 years or older) to the patterns for
      women in midlife (32 to 65 years). Study participants indicated that health,
      convenience, work or time constraints, or personal preferences were factors that
      most interfered with their attending the programs. Age was not a factor.

PMID- 12004563
TI  - Catastrophizing and health-related quality of life: a 6-year follow-up of
      patients with chronic low back pain.
AB  - A pain rehabilitation model that focused on emotions was implemented to influence
      catastrophizing by, and health-related quality of life (HRQL) for, persons with
      chronic low back pain. Twelve individuals, 7 men and 5 women (aged 33 to 57
      years), all with long-term pain despite treatment, were included in the study and
      a single case research experimental design (SCRED) was used to follow the
      patterns of coping with pain for 6 years. The HRQL was measured before and 6
      years after the intervention. Coping strategies and HRQL were evaluated with the
      Coping Strategy Questionnaire (CSQ) and the SF-36, respectively. The evaluation
      of pain coping strategies after 3 years found decreased catastrophizing, a
      decrease that had continued 3 years later. HRQL showed significantly improved
      mental health and impaired physical capacity at the 6-year follow-up. Changes in
      catastrophizing or in HRQL did not appear to influence self-scored bodily pain.
      Altered catastrophizing appeared to be a long-term process. This research
      indicates the need for rehabilitation programs to assess and evaluate patients'
      pain and their need for improved quality of life, rather than focusing only on
      the elimination of pain.

PMID- 12004564
TI  - National Consensus Conference on Improving the Continuum of Care for Patients
      with Hip Fracture. May 3-4, 2001, Washington, DC.

PMID- 12004565
TI  - A most difficult journey.

PMID- 12004566
TI  - Fatigue and stroke.
AB  - Under disabling conditions such as stroke, fatigue may worsen other symptoms and
      impede full participation in a rehabilitation program. The functional improvement
      needed to regain mobility and independence may be impacted significantly by
      fatigue. This article explores the symptom of fatigue and its relation to stroke
      from a rehabilitation perspective. It examines theoretical models, operational
      definitions, fatigue as a response to stroke, assessment and measurement
      instruments, symptom management strategies, and future research directions.

PMID- 12004567
TI  - Recovery trajectory of unpartnered elders after myocardial infarction: an
      analysis of daily diaries.
AB  - The study reported here analyzed daily diary entries of unpartnered elders after
      myocardial infarction (MI) to gain perspective into their recovery. A total of 33
      diaries were included as part of the qualitative analysis of the larger study
      referred to above. Diary content was evaluated through qualitative descriptive
      analysis. Six categories--activities of daily living, exercise practices, social
      support, symptom reporting, healthcare activities, and health-related expenses-
      were identified from the diaries. Results suggest that recovering, unpartnered MI
      elders have a need to return to a familiar lifestyle. Moreover, a few differences
      and similarities based on gender were found. In the rehabilitation setting,
      nurses should recognize the need for elders to return to normal activities, the
      importance of social support, the acknowledgement of gender differences, and the
      potential cost burden for these patients. Diaries were a valuable tool with which
      to uncover information about the recovery trajectory of unpartnered elders after
      MI.

PMID- 12004568
TI  - Proteolysis of endomorphin-1 by brain synaptic membrane-associated peptidases.
AB  - The biotransformation of endomorphin-1 (EM-1) by brain synaptic membranes has
      been studied. Peptide fragments of EM-1 that were formed during incubation with
      membrane preparations in vitro were isolated by High-performance liquid
      chromatography (HPLC) and characterized using determination of amino acid
      composition. At pH 7.4, two degradation products, EM-1(1-3) and EM-1(1-2), were
      identified. EM-1 was degraded 77.5% at 30 min incubation with synaptic membranes.
      The time course of the experiments and the effect of carboxypeptidase inhibitor
      (CPI) demonstrated that the proteolysis reaction involves the participation of
      carboxypeptidase activity.

PMID- 12004569
TI  - Superior laryngeal nerve section abolishes capsaicin evoked chemoreflex in
      anaesthetized rats.
AB  - Respiratory effects of an intravenous injection of capsaicin were investigated in
      nine vagotomized and subsequently laryngeally deafferentated, urethane- and
      chloralose-anaesthetized and spontaneously breathing rats. Bolus injection of
      capsaicin (5 micrograms/kg) into the right femoral vein induced an expiratory
      apnoea of 4.23 +/- 0.63 s duration (mean +/- SEM). In post-apnoeic breathing,
      tidal volume increased by 14% from the control level (P < 0.05) in all nine rats
      treated by vagotomy. Section of the superior laryngeal nerves (SLNs) precluded
      the occurrence of apnoea. Results of this study indicate that in vagotomized rats
      sensory input from the larynx constitutes an important pathway to the nodose
      ganglia endowed with capsaicin receptors.

PMID- 12004570
TI  - Effects of social rearing conditions on conditioned suppression in rats.
AB  - Twenty-two rats were reared in standard conditions during the first two months of
      their life. Then the animals were divided into two groups exposed to different
      rearing conditions. Twelve animals (Group SO) were housed socially, six animals
      per cage, and for three weeks they were subjected to sensory stimulation in an
      enriched environment. The other ten subjects were kept individually (Group IN);
      one rat per mesh cage, in conditions of relatively impoverished sensory
      stimulation. In both groups the training of the conditioned emotional response
      (CER) was performed when animals were three months old. In contrast to IN
      subjects, the rats subjected to permanent social contacts and reared in the
      enriched environment (Group SO) revealed almost equally low instrumental response
      rates in trials with the conditioned stimulus (CS) paired with nociceptive foot
      shock (US), and in periods when no CS and/or US were applied. The results
      suggested that early exposure to an enriched environment caused a later decrease
      of the animals' capability to differentiate between the aversive CS and cues of
      the experimental context. This cognitive impairment was probably a secondary
      effect of fear generalized to the entire experimental situation.

PMID- 12004571
TI  - Perception of facial affect in chronic schizophrenia and right brain damage.
AB  - This study was designed to compare the performance of 50 chronic schizophrenics
      (CS) to that of 30 right brain-damaged patients (R), and 50 healthy controls (N)
      on several facial perception measures: Emotion Labelling and Recognition, and the
      Benton Facial Recognition Test. CSs were diagnosed according to DSM-IV criteria
      and their psychiatric state was assessed using the PANSS scale. All subjects were
      right handed. Their cognitive state was assessed using the MMSE. Subjects rated
      their current mood on a visual analogue scale. The results showed that the CSs
      and Rs were significantly impaired compared to Ns for the emotional tasks but did
      not differ from each other. Moreover, the patient groups were significantly less
      accurate in recognising emotionally neutral facial stimuli. Each subject group
      had more difficulty processing negative relative to positive affect. The deficit
      in schizophrenia was found to be stable, which may reflect a trait-like, rather
      than a state-dependent, characteristic. Moreover, some support is provided for
      the notion that facial affect perception in chronic schizophrenia is associated
      with right hemisphere dysfunction.

PMID- 12004572
TI  - Hypoxic damage of the cerebellum in 7-day-old rats. Ultrastructural and
      histochemical study.
AB  - The damaging influence of hypoxia on the cerebellum in immature rats, which is
      still discussed, was investigated. Using material obtained in a modified Levine
      model for combined hypoxic-ischemic damage in 7-day-old rats, we examined changes
      in cerebellum submitted to hypoxia only. The results demonstrated classic
      features of hypoxic nervous tissue damage and calcium accumulation in
      mitochondria and endoplasmic reticulum. This was investigated using electron
      microscopy combined with the oxalate-pyroantimonate method. We propose that Ca2+
      increases in endoplasmic reticulum and mitochondrial Ca2+ pools may be involved
      in damage-mediated mechanisms. These results support a role of calcium as a
      mechanism of cerebellar cell loss after this form of injury.

PMID- 12004573
TI  - The time course of the last contractions during incompletely fused tetani of
      motor units in rat skeletal muscle.
AB  - The time course of the contraction and the relaxation of individual contractions
      during incompletely fused tetani of motor units were analyzed. Investigations
      were performed on fast fatigable (FF), fast resistant (FR) and slow (S) motor
      units of the rat medial gastrocnemius muscle. Stimulation of a motor unit with a
      series of nine trains of stimuli at a frequency from 10 to 150 Hz was used and
      tetani fused to a variable degree were recorded. For fast motor units the
      procedure was repeated twice and observations were made on potentiated tetani in
      the second series of stimulation. For each tetanus, the amplitude of the tension
      increase, the peak amplitude of the contraction, the contraction time and the
      half-relaxation time were measured in the last contraction of the tension
      recording. It was observed in all three types of motor units that the last
      contraction was prolonged in parallel with the increase of fusion of a tetanus.
      In this contraction, the contraction time slightly decreased whereas the half
      relaxation time strongly prolonged. The prolongation of the half-relaxation time
      was the strongest in tetani of slow units. Moreover, for the last contraction in
      a tetanus, the rate of changes in tension were studied. The rate of increase in
      tension during the contraction decreased in parallel with the increase of fusion
      of a tetanus, whereas the maximal rate of the tension decrease during the
      relaxation was found in tetani with fusion indices of 0.79, 0.98 and 0.95 for FF,
      FR and S motor units, respectively. Changes in the time course of contractions in
      tetani fused to a variable degree can shed light on processes of summation of
      contractions in unfused tetani at the level of individual motor units.

PMID- 12004574
TI  - [Brown fat tissue in humans].
AB  - Brown adipose tissue (BAT) is universally present in mammals. Thermal production
      in such tissue is physiologically important for maintaining temperature
      homeostasis and regulation of body mass in small-size homoiotherms. At present it
      is clearly established that unlike other large mammals, brown adipose in man and
      primates is retained throughout the whole postnatal othogenesis. Therefore, BAT
      appears as a possible effector of pharmacogenetic protection from human excessive
      adiposis. Systematic reserach of various functioning aspects of this unique organ
      of mammals were started abroad as early as 1960-es, and are actively developing
      at present. Domestic research of energy circulation physiology and of
      thermoregulation developed mostly outside the brown adipose tissue. Therefore,
      the principal objective of this publication is to draw attention of experimental
      and clinical researches to an intriguing aspect of the issue of energy
      circulation in humans--the issue of brown adipose functioning.

PMID- 12004575
TI  - [Neuroimmunoendocrinology of the fat tissue].
AB  - Recent information concerning the white fat tissue allows considering it as
      endocrine system involved in the neuro-immune-endocrine interactions in
      regulating various aspects of homeostasis. The contribution presented sums up the
      latest evidence of adipocyte secreting hormones (leptine and resistine), cytokine
      (TNF alpha), as well as shedlight on mechanisms, involved in control of energy
      metabolism, immune reactions and food intake monitoring.

PMID- 12004576
TI  - [Subtype-specific clinically important effects of alpha 2-adrenergic receptors].
AB  - A- B- and C-subtypes of alpha 2-adrenoreceptors present in all mammals are
      involved in responses to currently existing subtype-nonselective ligands of these
      receptors widely used in medicine. Each of the subtypes has its own specific
      distribution in tissue and cells, onthogenetic pattern, specific regulation of
      activity and expression, and, as result, specific physiological functions. The
      latter suggests opportunities of using the subtype-specific for correction of the
      functions depending on this receptor. The article reviews the role of individual
      subtypes of alpha 2-adrenoreceptors in regulation of neurochemical transmission
      of cardiovascular system, psychoemotional state and development of psychic
      disorders, and also male sexual behaviour.

PMID- 12004577
TI  - [NO-Ergic transmission and NO as a volume transmitter. Effect of NO on mechanisms
      of synaptic plasticity and epileptogenesis].
AB  - Nitric oxide (NO) is a universal intercellular messenger and the only molecule
      known so far, which satisfies all requirements of the volume (extrasynaptic)
      neurotransmitter. The effect of NO on target cells is so read in the four
      dimensional coordinate system by combining both the spatial and the temporal
      components of the nervous activity. In this review, the authors, based on
      literature data and own studies, present a detailed analysis of properties of NO
      as a volume neurotransmitter at formation of phenomena of synaptic plasticity in
      norm and pathology. An evaluation is given of cytotoxic and neuroprotective
      effects of NO under conditions of the brain tissue ischemia and phenomena of
      hyperexcitability in foci of epileptiform activity. It is emphasized that the
      long-term potentiation and long-term depression, phenomena of physiological
      plasticity, can be transformed into pathological plasticity at disturbances of
      equilibrium between neuroprotective and neurotoxic effects of NO.

PMID- 12004578
TI  - [Prenatal hypoxic stress: physiological and biochemical consequences, correction
      by regulator peptides].
AB  - The review is devoted to the problem of prenatal hypoxia influence on central and
      vegetative nervous system, cardio-vascular and respiratory systems, cell
      metabolism. It is shown that perinatal hypoxia is often resulted in severe non
      reversal functional disorders of postnatal development based on significant
      morphological changes. Regulatory peptide pretreatment is discussed as one of the
      methods for correction of pre- and postnatal hypoxic consequences.

PMID- 12004579
TI  - [Electrophysiological study of the choice motivation in man].
AB  - In 70 Ss EEG coherence, amplitude and frequency characteristics as well as formal
      dynamic (temperamental) properties were compared with the two dimensions of
      motivation involved in the choice of profession--its subjective "value" and the
      probability of its achievement ("accessability"). It was shown that the persons
      orienting themselves to the subjective value of the future profession tend to
      possess those features of temperament that testify to the stronger, more mobile
      and more labile nervous system as distinct from the subjects orienting themselves
      to the higher level of accessability. It was also shown that the persons with a
      higher level of the subjective value had a much higher level of EEG cortical
      activation in both hemispheres of the brain. The subjects with higher magnitudes
      of "accessability" were characterized by a lower level of brain activation.

PMID- 12004580
TI  - [Isoflavones and calcified tissues].
AB  - The data about osteotropic action of isoflavones are presented in this review.
      Isoflavones are the compounds of phytoestrogenes group--hormone-like
      bioregulators of plant origin. Animal experiments as well as bone tissue and bone
      cells cultures investigations demonstrate anabolic effect of isoflavones on bone
      metabolism. Isoflavones prevent bone loss in ovariectomized animals. They inhibit
      bone resorbition and enhance bone formation. Because of this natural and
      synthetic isoflavones hold great promise in the prevention and treatment of
      osteoporosis. These compounds may also be effective in preventing bone loss
      associated with hypodynamia or immobility, ovariectomy or postmenopausal
      hypoestrogenia, chronic corticosteroid use, renal osteodystrophy,
      hyperparathyroidism and other metabolic disorders affecting the calcified
      tissues, including alveolar bone loss in periodontal disease as well as dental
      hard tissues destruction.

PMID- 12004581
TI  - The effect of the Senior Citizens' Freedom to Work Act of 2000 on employer
      provided pension and medical plans.
AB  - On April 7, 2000 President Clinton signed the Senior Citizens' Freedom to Work
      Act. The act reduces the Social Security retirement benefit penalties previously
      imposed on 65- through 69-year-old workers who earned more than nominal incomes
      after enrolling in the program. This article analyzes the impact that the act
      will have on retirement decisions of the affected cohorts of older workers and
      closes with an analysis of how the act may affect employer-provided pension,
      medical and paid leave plans.

PMID- 12004582
TI  - Long-term care financing: options for the future.
AB  - The aging of the baby boomers will have an enormous impact on the future of long
      term care costs. This article projects the magnitude of that impact, discusses
      sources of financing, and considers the cost and feasibility of three options for
      financing future long-term care services. The authors investigate the
      alternatives of increasing personal savings, raising payroll taxes and expanding
      employer-sponsored private long-term care insurance coverage, respectively.

PMID- 12004583
TI  - The mental health paradox.
AB  - The authors review the evidence that mental health coverage pays for itself by
      reducing overall health care costs, satisfies and helps patients who receive it,
      reduces employee absenteeism and improves employee functioning. They then explain
      the factors contributing to the decline in mental health services valuations and
      what employers can do to minimize them.

PMID- 12004585
TI  - The launch of NEHA Training LLC.

PMID- 12004584
TI  - A Norwalk-like virus outbreak on the Appalachian Trail.
AB  - In May and June 1999, an outbreak of acute gastrointestinal illness occurred
      among long-distance hikers on the Appalachian Trail between Catawba and
      Troutville, Virginia. An investigation found that 45 out of 70 hikers had become
      ill within two days of arriving in Catawba, Virginia. Water samples were
      collected from a general store frequented by the hikers and from several nearby
      buildings and a popular all-you-can-eat restaurant. Symptoms were consistent with
      those caused by Norwalk-like viruses, and laboratory diagnosis detected Norwalk
      like viruses in stool and serum specimens. People who consumed food items
      prepared at the general store were almost twice as likely to become ill as
      persons who did not consume those foods. Environmental sampling of water from the
      taps inside and outside the general store and from several surrounding
      establishments in Catawba found contamination by fecal coliform bacteria but not
      by Norwalk-like virus. Since several hikers reported illness prior to arriving at
      Catawba, person-to-person transmission of a highly contagious agent such as
      Norwalk-like virus could not be ruled out. Poor sanitation, scarce water
      supplies, and crowding can increase the risk of gastrointestinal illness among
      long-distance hikers.

PMID- 12004586
TI  - Model for success in on-site wastewater management.

PMID- 12004587
TI  - Water, water, everywhere.

PMID- 12004588
TI  - What we know and what we do: the gap in food safety.

PMID- 12004589
TI  - A primer on sampling for biological contaminants--Part One: Science and theory.

PMID- 12004590
TI  - How the immune system eliminates mosquito-borne viruses--new insights.

PMID- 12004591
TI  - A new phage may help control pathogens on fresh-cut produce.

PMID- 12004592
TI  - Water demand triggers crisis in China.

PMID- 12004593
TI  - The use of antimicrobials outside human medicine: information from the World
      Health Organization on the health consequences.

PMID- 12004594
TI  - Post September 11: some reflections on the role of environmental health in
      terrorism response.

PMID- 12004595
TI  - Salmonella and other Enterobacteriaceae in dairy-cow feed ingredients:
      antimicrobial resistance in western Oregon.
AB  - Several studies have suggested an association between the use of antimicrobial
      agents in animal feeds and an increased risk that humans will contract resistant
      strains of bacteria such as Salmonella species, Escherichia coli, and other
      enteric isolates. The authors of this study evaluated whether animal feeds might
      serve as sources of antimicrobial-resistant bacteria, especially bacteria that
      are pathogenic to humans. From July through August 1998, samples of feed
      ingredients were collected from a total of 50 feed piles located on 12 dairy
      farms in western Oregon. From a subset of 10 piles, repeated samples were
      collected over time until each pile was depleted. Analysis of the samples
      indicated that 42.0 percent of all 50 piles and 60.0 percent of the piles from
      which there was repeated sampling were presumptive positive for Salmonella. Sixty
      two percent of 50 Enterobacteriaceae isolates showed ampicillin resistance, and
      10.0 percent displayed tetracycline resistance. Other bacteria displayed varying
      degrees of resistance to ampicillin, streptomycin, tetracycline, or a combination
      of these antimicrobials. The extent of antimicrobial-resistant Enterobacteriaceae
      in feed ingredients observed in this study raises significant concerns about the
      potential for human health risks from food-producing animals such as dairy cows.

PMID- 12004596
TI  - Of costs and caregivers. Analyzing the impact of staffing recommendations.

PMID- 12004597
TI  - Home care comes of age. A place of its own in the continuum of long-term care.

PMID- 12004598
TI  - Non-invasive method overcomes incontinence. Program retrains residents to
      recognize the urge to void.

PMID- 12004599
TI  - He said, she said: executive roundtable. Interview by Susanne Bilyeu and Joyce
      Pagan.

PMID- 12004600
TI  - Let the healing begin.

PMID- 12004601
TI  - Tame runaway cost creep. Eroding margins are a serious problem.

PMID- 12004602
TI  - It could happen to you. Interview by Mark Zacharia.

PMID- 12004603
TI  - [Comparison of cytogenetic response of human lymphocytes to in vivo and in vitro
      exposure to low-dose gamma rays. Translocations and dicentrics detected by the
      FISH technique].
AB  - On peripheral lymphocytes of 5 cancer patients undergone wholebody therapeutic
      irradiation (at daily dose of 10 cGy up to total dose 50 cGy of 60Co gamma-rays)
      the dose response of unstable and stable chromosomal exchanges detected by FISH
      was compared with the dose response of the some aberrations in lymphocytes
      irradiated in vitro. The dose response fitted well to linear function. For
      dicentrics the lower slope of dose-response curve was found for in vivo
      irradiated lymphocytes as compared to the dose-response curve obtained for in
      vitro irradiated lymphocytes of the same patients. No difference between in vivo
      and in vitro irradiation of lymphocytes was found for translocations. The
      frequency of translocations increased faster with the dose than the frequency of
      dicentrics only in lymphocytes irradiated in vivo.

PMID- 12004604
TI  - [Study on genetic radioresistance of natural Drosophila Melanogaster population
      from radionuclide contaminated regions of Byelarus].
AB  - Over the period from 1998 to 2000 adaptation to unfavorable ecological factors
      was revealed to be formed in natural Drosophila melanogaster populations from
      various regions of Belarus with increased radiation background due to the
      Chernobyl accident. This adaptation was shown to be of non-specific character,
      since the populations from radiation regions were more resistant to the effect of
      not only factors of physical nature (irradiation), but also to that of chemical
      mutagen ethylmethanesulphonate. Assessment of population resistance was carried
      out by means of tests of dominant lethal mutations and recessive sex-linked
      lethal mutations.

PMID- 12004605
TI  - [Radioadaptive response in vitro of unstimulated rat lymphocytes according to
      metallothionein test].
AB  - It was shown that 24 h after acute action of gamma-radiation in vitro on
      unstimulated rat lymphocytes the metallothionein (MT) level did not change for
      doses of 0.01; 0.5 and 1.0 Gy, while dosed of 1.75 and 2.5 Gy increased this
      parameter 2 and 2.6 times on the average. After exposure to 0.01 Gy of adaptive
      radiation 2 h before exposure to 1.75 Gy of the damaging dose reliably lower (1.5
      times on the average) increase in MT content was found. The heterogeneity in
      display of the radioadaptive response by MT test for various lymphocyte
      preparations was found. Two possible mechanisms of the obtained changes were
      discussed. One of them is connected with the selection irradiation death of cells
      with the initially low MT level, and the other is caused by postradiation MT
      synthesis as a result of accumulation of the DNA damages and MT genes
      amplification.

PMID- 12004606
TI  - [Morphofunctional state of the rat male reproductive system after chronic low
      intensity irradiation at a dose of 1.0 Gy].
AB  - It was studied the morphofunctional state of rat male reproductive system after
      chronically exposure to low intensive gamma-irradiation in early ontogenesis.
      After radiation with a total dose of 1.0 Gy it was revealed the decrease of the
      testes and epididymis weight, dysbalance in the ratio of different spermatogenic
      cells, changes in nucleic acid content and discoordination of bioenergetic
      metabolism in testes. Disturbance in rat male reproductive system retained in
      remote period (180 days after irradiation).

PMID- 12004607
TI  - [Seasonal changes in tumor necrosis factor production in hibernating animals in
      normal conditions and under the effects of electromagnetic and ionizing
      radiation].
AB  - Production of tumor necrosis factor (TNF) has been investigated in peritoneal
      macrophages and splenic T cells of Arctic Yakutian ground squirrel (Citellus
      Undulatus Pallas) upon in vitro action of electromagnetic and ionizing radiation
      during annual cycle. The significant activation of TNF production in the cells of
      awaken ground squirrels in winter and increasing level of the lymphokine
      production at spring-summer period has been indicated. The level of TNF
      production in splenic T cells was not changed during whole year. The
      electromagnetic radiation (EMR) of low intensity (8.15-18 GHz, 1 microW/cm2)
      induced an augmentation of both secretory and proliferative activity in TNF
      producing cells. Ionizing radiation suppressed T cell proliferation, but the
      doses 2 and 5 Gy resulted in a significant stimulation of TNF production in T
      cells and macrophages.

PMID- 12004608
TI  - [Damage to macrophage membranes by exposure to middle-wave ultraviolet
      radiation].
AB  - An influence of middle-wave ultraviolet radiation (lambda max = 306 nm) on plasma
      membranes of mice peritoneal macrophages was studied by microfluorimetry
      analysis. It was found that a percentage of cells with damaged plasma membranes
      in the irradiated macrophage population reliably increased with the UVB dose
      starting with 6 J/cm2. Irradiation of cells with 4.2 J/cm2 UVR dose which does
      not cause evident damage to plasma membranes led to the latent damage which was
      detected by treatment with detergent digitonin (4.5 micrograms/ml).

PMID- 12004609
TI  - [Modification of damaging effect of ultraviolet radiation on peritoneal
      macrophage membranes in mice].
AB  - Different factors modificating damaging effect of middle-wave ultraviolet
      radiation (lambda max = 306 nm) on mice peritoneal macrophage plasma membranes
      were studied. It was shown that damaging effect of ultraviolet declined when the
      cells were simultaneously treated by red light (lambda max = 713 nm). This
      protective effect increased when a red component of light became greater and
      achieved almost 100% when it consisted 28.6%. It was also found that the decrease
      in intra- and extracellular pH led to the decrease in damaging effect of UVR. The
      increase of pH bring to an elevation of UVR destructive effect.

PMID- 12004610
TI  - [Effects of chronic irradiation on the adaptive potential of plants].
AB  - The content of anthocianins was determined in Oenothera biennis plants, grown
      from seeds, picked on the plots with different levels of radionuclide
      contamination in the 30-km Chernobyl zone. It was shown that the content of
      anthocianins was higher in plants from Yanov area (20-40 mR/h) than in plants
      from Chernobyl area (0.04 mR/h). An acute gamma-irradiation of seeds with a dose
      of 5-100 Gy or UV-irradiation of plants resulted in increasing of anthocianin
      content which was higher in plants grown from the seeds picked on plots with a
      low level of radionuclide contamination. The data obtained suggest that chronic
      irradiation of O. biennis populations induces accumulation of anthocianins.
      Apparently the adaptivity potential has been more completely realised in plants
      on the plots with a higher level of radionuclide contamination. The populations
      which were formed in the absence or at the low level of radionuclide
      contamination, on the contrary, have a significant adaptivity potential and,
      accordingly, higher radioresistance.

PMID- 12004611
TI  - [Influence of ionizing radiation of low intensity on the processes of
      reproduction, aging and dying off of Escherichia coli bacteria].
AB  - The influence of 60Co gamma-ray irradiation of low intensity (0.1-0.4, 0.76 x
      10(3) microGy/h) on the processes of reproduction, aging and dying off of E. coli
      B/r and E. coli BS-1 bacteria have been investigated. It was shown that the
      reproduction of this bacteria strains was not dependent on the dose rate in the
      range 0.1-0.4 microGy/h. It was shown in comparison with the irradiated E. coli
      B/r cells dynamics of the aging and dying off of the irradiated E. coli BS-1 is
      decreased in the process of prolonged (about 190 days) irradiation with a dose
      rate of 0.76 x 10(3) microGy/h. It is proposed the relationship between the
      revealed phenomenon of the decrease in the intensity of the irradiated E. coli BS
      1 cell aging and dying and the Vavilov-Cerenkov emission.

PMID- 12004612
TI  - [Synthetic peptides -- analogs of biologically active fragment of the
      differentiation factor from HL-60 cells show radioprotective and adaptogenic
      activities].
AB  - It was shown that the addition of synthetic six-membered peptide (HLDF-6) and its
      Tyr-analog (HLDF-Y) to cultural medium significantly increased the survival of
      cells HL-60, treated by cold shock. The prophylactic administration of HDLF-Y (1
      mg/kg, 4 hours prior to applied actions) decreased the response of
      hypothalamushypophysis-adrenal glands system and sympathicoadrenal system of rat
      males on supercooling and also increased the resistance of mouse males to
      supercooling and X-irradiation. In the experiences with females HDLF-Y did not
      show the similar biological activity.

PMID- 12004613
TI  - [Effects of para-aminobenzoic acid on radiosensitivity of mice of different
      strains].
AB  - The aim of the work was to study the possible protective effect of para
      aminobenzoic acid (PABA) on the radiation lethality in mice of three inbred lines
      (BALB/cLacY, C3H/HeY, 101/Hy), stock YT1 and hybrids (C3H/He x 101/H)F1. The PABA
      solution was given to the mice intraperitoneally in single doses of 10, 50 and
      100 mg/kg 40-50 min prior to irradiation with doses of 6 to 8 Gy depending on the
      line and sex of mice. The used doses of gamma-radiation were roughly LD75/30. The
      radioprotective effect of PABA was observed in all variants of the experiment but
      it was relatively low. The protection coefficient varied from 0 to 0.45. The
      protective effect depended on the line and sex of mice and on the dose of the
      injected substance.

PMID- 12004614
TI  - [Effects of low intensity laser (632.8 nm) and ultraviolet radiation on spectral
      properties and functional activity of human ceruloplasmin].
AB  - Photoinduced changes of human ceruloplasmin (hCp) under laser and ultraviolet
      (UV) radiation have been studied. A complex character of hCp spectral
      modifications points to a different degree of the protein molecule folding. After
      the influence of UV radiation (240-390 nm) in a dose range 906-4530 J/m2 the
      decrease of oxidase hCp activity was registered. These changes are thought to be
      connected with modification of the conformation of hCp active centre or copper
      reduction that was confirmed by the decrease of optical density at 610 nm. An
      inactivation constant (kf = 3.8 x 10(-4) 1/s) and a photoinactivation quantum
      yield (1.4 x 10(-4)) were calculated. Kinetic dependencies of o-phenilen-diamine
      oxidation by intact and UV-modified glycoprotein do not correspond to Michaelis
      Menten equation. UV radiation in a dose range 151-4530 J/m2 induced increasing of
      ceruloplasmin superoxiddismutase activity. The influence of He-Ne laser radiation
      (1.3 mW; lambda = 632.8 nm, exposure time from 1 up to 30 min) leads to the raise
      of the hCp functional activity; superoxiddismutase activity changes more
      significantly. Possible photophysical and photochemical processes in hCp
      molecule, leading to photomodification and changes of protein functional activity
      have been represented on the scheme.

PMID- 12004615
TI  - [Study of the effects of laser irradiation (540 nm) on some components of blood
      enzyme antioxidant system].
AB  - The influence of blood laser irradiation (lambda = 540 nm) in doses range 0.3-1.2
      J/cm2 on the neutrophyles superoxide-dismutase and katalase activity has been
      studied. Correcting effect of laser light (0.6; 1.2 J/cm2) on the functional
      activity of studied enzymes has been found. The high degree of correlation (r =
      0.6) between neutrophil superoxide dismutase and neutrophil catalase activity of
      the irradiated blood has been discovered. The close correlation between
      components of the antioxidant system and processes of active oxygen metabolite
      generation has been revealed. The scheme of free radical mechanisms of the laser
      irradiation influence on the several parts of the enzyme antioxidant system has
      been suggested.

PMID- 12004616
TI  - [Dependence of microwave effect on the secondary structure of DNA on molecular
      weight of polynucleotide].
AB  - The effect of ultralow power pulse-modulated electromagnetic radiation (average
      power density 60 microW/cm2, carrying frequency 1.05; 2.12; or 2.39 GHz;
      modulating pulses with frequency 4 Hz) on the secondary structure of DNA was
      investigated. It was established that the exposure of beta-alanine and
      formaldehyde containing aqueous DNA solution to electromagnetic radiation had
      activated the process of DNA despiralization under the action of beta-alanine-
      formaldehyde reaction product. The effect of electromagnetic radiation on the
      secondary structure of DNA can be removed by lowering of molecular weight of DNA
      to 0.46 x 10(6) (at carrying frequency 1.05 GHz), or to 0.25 x 10(3) (at carrying
      frequency 2.39 GHz).

PMID- 12004617
TI  - [Effects of 460 MHz microwave radiation on Drosophila embryos under raised
      temperature].
AB  - Combined effect of 460-MHz microwave irradiation and increased (up to 40 degrees
      C) temperature on Drosophila embryos of definite age was studied. It was
      demonstrated that the effect of 5-min exposures to non-modulated microwaves with
      6 W/kg SAR accompanied with heating is only a little stronger than at normal
      temperature (24.5 degrees C). Irradiation with pulse-modulated microwaves with
      pulse repetition rates of 6, 10, 16, and 22 p.p.s. with average SAR of 0.12 W/kg
      (pulsed SAR 3 W/kg) combined with increased temperature caused some changes in
      PID dependent on the pulse rate. At 6 and 22 p.p.s, the increase in PID was close
      to that observed at normal temperature while at 10 and 16 p.p.s. the microwave
      irradiation did not produce any noticeable effect on development of the
      Drosophilas.

PMID- 12004618
TI  - [Accumulation of industrial radionuclides by the Yenisei River aquatic plants in
      the area affected by the activity of the mining and chemical plant].
AB  - The aim of the paper is to investigate accumulation of artificial radionuclides
      by the Yenisei River aquatic plants collected in the area affected by the
      activity of the Mining-and-Chemical Combine (Zheleznogorsk) from 1997 to 2000.
      The samples of aquatic plants were of four species: Potamogeton lucens,
      Fontinalis antipyretica, Elodea canadensis, and Ceratophyllum demersum. The gamma
      spectrometric analysis of the samples of aquatic plants for artificial
      radionuclides revealed a wide spectrum of long-half-life and short-half-life
      radionuclides. Radionuclides of activation origin were found in the aquatic
      plants taken both near the Combine and 200 km down of it. The data obtained
      suggest that the cooling water of the operating reactor is still being released
      into the Yenisei. The radiochemical analysis of aquatic plants revealed strontium
      and plutonium isotopes. Among the aquatic plants, the highest concentration
      factors for the principal radionuclides were recorded in Fontinalis antipyretica
      (water moss).

PMID- 12004619
TI  - [Experimental investigations of 211Am accumulation by macrophytes of the Yenisei
      River].
AB  - Experiments were carried out in which 241Am was added to water samples containing
      macrophytes of the Yenisei River, and the radionuclide absorption rates and
      concentration factors were determined for the plants. It has been shown that the
      water moss (Fontinalis antipyretica) has a higher capacity to accumulate 241Am
      than the Canadian pondweed (Elodea canadensis) does. The laboratory experiments
      revealed that the capacity of dead biomass of the Canadian pondweed to accumulate
      241Am is twice higher than that of living biomass. In contrast, no significant
      increase in 241Am accumulation by dead biomass of the water moss has been
      recorded. The transuranic element 241Am was firmly fixed by the plant biomass and
      was not released into water in the course of long-duration experiments.

PMID- 12004620
TI  - [Method of assessment of 137Cs biological availability in forest soil].
AB  - A method for quantitative assessment of 137Cs availability to plants in forest
      ecosystems on the basis of soil properties has been developed. It is shown that
      the experimental dependencies of 137Cs soil-to-plant transfer factor (TFag) for
      fern and bilberry on the bioavailability factor calculated on the basis of soil
      characteristics of root layer: 137Cs exchangeability, exchangeable Ca, effective
      selectivity coefficient, were satisfactory described by linear function. The
      advantage of the proposed method is that the necessary soil characteristics can
      be taken from the reference literature, evaluated using empirical correlations or
      determined with standard agrochemical procedures.

PMID- 12004621
TI  - [Evaluation of the effectiveness of protective measures for reduction of the
      rural population exposure related to contamination of forest ecosystems].
AB  - The contribution of different forest pathways to the irradiation of inhabitants
      of the forest settlements after the ChNPP accident is estimated. It has been
      shown that the long-term negative impact of forest ecosystems contaminated to the
      rural population requires application of special protective measures for a long
      time after the ChNPP accident.

PMID- 12004622
TI  - [Method to increase efficiency of irradiation of biological objects by electron
      beams].
AB  - The method has been proposed for active control of distribution of the dose
      caused by an electron beam passed through the medium. The method is based on the
      influence of magnetic field on charged particles and it allows concentrating of
      the absorbed dose in the prescribed area. To investigate this method the Monte
      Carlo simulations were carried out for 20-70 MeV electrons in 0.5-3 T magnetic
      field using GEANT program. From the obtained results it follows that in the
      uniform magnetic field the maximum in distribution of the electron beam dose
      appears and its shape is similar to Bregg's peak for heavy charged particles. The
      location of the maximum may be changed by varying beam energy and magnetic fields
      configuration. For 60-70 MeV beam the maximum may be obtained at the depth of 10
      15 cm that is convenient for radiotherapeutic usage.

PMID- 12004623
TI  - [Mathematical description of synergistic interactions of environment temperature
      and microwaves for animal warming].
AB  - For mathematical description of synergetic interaction of high environmental
      temperature and microwaves for animal heating, a simple semi-empirical model was
      used. In the model, it is suggested that the mechanism of synergistic interaction
      is caused by the additional effective damages resulting in more higher body
      temperature increment comparing with that expected for the independent action of
      each agents. These additional damages are supposed to be produced by the
      interaction of sublesions induces by each agent and which are ineffective for
      their separate action. Utilizing the results published for rabbits [15], it was
      demonstrated that the model describes experimental data, predicts the highest
      synergistic effect and the condition under which it can be achieved. The data
      obtained may be useful for the assessment of microwave exposure safe levels.

PMID- 12004624
TI  - [15 years after the accident at the Chernobyl Nuclear Power Plant].
AB  - Health effects as a result of the accident at the Chernobyl nuclear power plant
      occurred in 1986 are considered in the paper. Wrong prognosis of the health
      effects with respect to mortality and morbidity among the population exposed to
      low radiation doses is shown. Proven increase in thyroid cancer cases among
      people who were children aged from 0 to 18 at the time of the accident is shown.
      Linear relationship between thyroid cancer cases and dose to thyroid ranged from
      0.2 to 4.0 Gy is considered. An additional absolute risk of thyroid cancer in
      children varies in the range 1.9-2.6 cases per 10(4) person-year Gy. During the
      fifteen years following the accident no cases of acute and chronic radiation
      sickness have been revealed because the population living in contaminated areas
      received low radiation doses. Also, exposures to low radiation doses did not
      result in excess of malignant tumors among population. In some cases the outcomes
      of acute radiation sickness were as follows: radiation damages to the skin,
      cancer cataracts, development of oncopathology.

PMID- 12004625
TI  - Expanding systemic links.

PMID- 12004626
TI  - Imagine the truth.

PMID- 12004627
TI  - Direct restoration of anterior teeth: review of the clinical technique and case
      presentation.
AB  - Direct composite resin bonding procedures are growing in popularity as
      conservative and predictable restorative treatment alternatives. An understanding
      of the fundamental layering, contouring, and polishing principles is paramount to
      the success of any direct composite restoration; this awareness can be
      subsequently applied to indirect restorations and significantly enhance
      laboratory/clinician communication. This article presents a clinical technique
      that describes the incremental placement of direct resin veneers on a typodont
      and demonstrates the application of these procedures on an actual clinical case.

PMID- 12004628
TI  - Indirect resin restoration using the "composite flask" system.

PMID- 12004629
TI  - Using pressable ceramics to achieve orthodontic correction.

PMID- 12004630
TI  - Applied techniques for predictable suture placement: Part 1.

PMID- 12004631
TI  - Salvaging fractured porcelain crowns with a direct composite repair technique.
AB  - Fractures of porcelain crowns, particularly on anterior teeth, require a rapid
      resolution. While repair can be achieved with relative ease using a composite
      resin material, detailed investigation of the cause of the fracture is mandatory
      to avoid repetition, and to safeguard longevity of both the affected restoration
      and abutment tooth. Treatment of fractured prostheses should not be implemented
      unless thorough evaluation is performed to determine potential damage to abutment
      and surrounding teeth. The ensuing discussion highlights etiology, clinical
      presentations, and guidelines for repairing fractured restorations.

PMID- 12004632
TI  - Image-guided navigational implantology.

PMID- 12004633
TI  - Predictable patient communication using trial porcelain veneers.

PMID- 12004634
TI  - The injection-molded technique for anterior maxillary provisional restorations: a
      clinical case.
AB  - Provisional restorations provide valuable clinical information for the definitive
      restorations. In the provisionalization phase, they guide the healing of the
      gingival tissues and allow the clinician to determine any necessary phonetic or
      aesthetic adjustments; provisional restorations also assuage patients'
      psychological concerns regarding their appearance. This article highlights the
      development of provisionalization procedures and describes disadvantages that
      have furthered the quest for improvements. An alternative technique for
      fabricating provisional restorations through an injection-molding process is
      demonstrated for the anterior maxilla.

PMID- 12004635
TI  - Assessing salivary gland hypofunction--Part two.

PMID- 12004636
TI  - Can we alter physician behavior by educational methods? Lessons learned from
      studies of the management and follow-up of hypertension.
AB  - INTRODUCTION: As expectations for effective continuing medical education (CME)
      grow, so, too, does the need to identify relationships among educational methods,
      physician performance, and patient outcomes associated with specific disease
      entities. Thus, we set out to review the literature on the effectiveness of
      physician educational interventions in the management and follow-up of
      hypertension. METHOD: We searched PubMed and the Research and Development
      Resource Base in Continuing Medical Education for randomized controlled trials of
      physician educational interventions. We included only those studies that (a) used
      replicable educational interventions with > 50% physician involvement and that
      employed objective methods to measure physician behavior change or patient
      outcomes, (b) indicated a physician or patient dropout rate of < 30%, and (c)
      followed outcome measurement for > 30 days. Studies were designated "positive" if
      one or more of the primary outcome measures demonstrated a statistically
      significant change in physician performance or health care outcome. RESULTS: We
      found 12 studies in which 7 different physician educational interventions were
      employed, alone or in combination, including reminders (computer or chart),
      formal CME, computerized decision support systems/risk stratification, printed
      educational materials, academic detailing, continuous quality improvement
      projects, and disease management aids in patient charts. Of the 12, 7 were
      positive and 4 were negative. One had mixed results. DISCUSSION: Although
      physician educational interventions, especially reminders, improved the follow-up
      of hypertension, they were ineffective in changing blood pressure levels.
      However, they may have some utility in improving compliance with guideline
      recommendations.

PMID- 12004637
TI  - Improving blood pressure control in diabetes: limitations of a clinical reminder
      in influencing physician behavior.
AB  - INTRODUCTION: Hypertension should be aggressively treated, especially in diabetic
      patients. But studies of physician prescribing habits reveal that physicians
      often delay making medication changes or initiating antihypertensive therapy. A
      chart-based reminder was designed to improve physician medication prescribing in
      this clinical situation. METHODS: A randomized controlled trial was conducted at
      the Veterans Affairs Medical Center in Richmond, Virginia. Patients with diabetes
      and hypertension were selected. A highly visible chart reminder was applied to
      the front of outpatient charts in the intervention group practice. A chart review
      was conducted to assess physician-directed medication changes. A successful
      outcome was defined as any antihypertensive medication increase or addition at
      that same visit. RESULTS: Physicians were more likely to intensify
      antihypertensive medication as the blood pressure increased regardless of the
      reminder. Overall, only 33% of visits resulted in a medication change, even
      though 93% of patients had elevations over target blood pressure at the follow-up
      visit. Physicians in the intervention and control groups made changes to
      medication at similar rates (chi 2 = 0.621, p = .511). DISCUSSION: In this study,
      a chart reminder failed to improve physician compliance with the clinical
      guideline for hypertension management in diabetics, Sixth Report of the Joint
      National Committee on the Detection, Evaluation, Prevention and Treatment of High
      Blood Pressure. To inform the design of effective intervention strategies,
      further research should explore specific barriers to guideline adherence in this
      clinical situation.

PMID- 12004638
TI  - Developing professional judgment.
AB  - The concept of professional judgment is considered, including its theoretical
      foundations, how it is developed, and how it may be assessed. Professionals are
      asked to engage in complex and unpredictable tasks on society's behalf, and in
      doing so must exercise their discretion, making judgments--decide what is "best"
      in the particular situation rather than what is "right" in some absolute sense.
      Inevitably, some of these judgments lead to "error," which is endemic to
      professional practice. This challenges some current ideologies in health care
      regarding the primacy of evidence-based practice and the application of
      protocols. At the foundation of professional judgment is a form of knowledge-
      called practical wisdom--which is not formally taught and learnt but is acquired
      largely through experience and informal conversations with respected peers.
      Wisdom develops through "the critical reconstruction of practice," including
      deliberation, which is distinguished from mere reflection. Professionals need to
      engage in the appreciation of their practice--not just to understand what informs
      their own practice but to consider critically the contestable issues endemic to
      practicing as a professional.

PMID- 12004639
TI  - Physician Internet medical information seeking and on-line continuing education
      use patterns.
AB  - INTRODUCTION: Although physician Internet use patterns have been studied, little
      attention has been paid to how current physician learning and change theories
      relate to physician Internet information seeking and on-line learning behaviors.
      The purpose of this study was to examine physician medical information-seeking
      behaviors and their relevance to continuing education (CE) providers who design
      and develop on-line CE activities. METHODS: A survey concerning Internet use and
      learning was administered by facsimile transmission to a random sample of 2,200
      U.S. office-based physicians of all specialties. RESULTS: Nearly all physicians
      have access to the Internet, know how to use it, and access it for medical
      information; the Internet's professional importance to physicians currently is in
      the area of professional development and information seeking to provide better
      care rather than for patient-physician communication. A particular patient
      problem was the most common reason for seeking information. The credibility of
      the source, quick and 24-hour access to information, and ease of searching were
      most important to physicians. Barriers to use included too much information to
      scan and too little specific information to respond to a defined question.
      DISCUSSION: The importance of the Internet to physician professional development
      is growing rapidly. Access to on-line continuing medical education must be
      immediate, relevant, credible, and easy to use. A sense of high utility demands
      content that is focused and well indexed. The roles of the CE provider must be
      reshaped to include helping physicians seek and construct the kind of knowledge
      they need to improve patient care.

PMID- 12004640
TI  - Academia-industry collaboration in continuing medical education: description of
      two approaches.
AB  - INTRODUCTION: Although concerns have been raised about industry support of
      continuing medical education (CME), there are few published reports of academia
      industry collaboration in the field. We describe and evaluate Pri-Med, a CME
      experience for primary care clinicians developed jointly by the Harvard Medical
      School (HMS) and M/C Communications. METHODS: Since 1995, 19 Pri-Med conferences
      have been held in four cities, drawing more than 100,000 primary care clinicians.
      The educational core of each Pri-Med conference is a 3-day Harvard course,
      "Current Clinical Issues in Primary Care." Course content is determined by a
      faculty committee independent of any commercial influence. Revenues from multiple
      industry sources flow through M/C Communications to the medical school as an
      educational grant to support primary care education. Pri-Med also offers separate
      pharmaceutical company-funded symposia. RESULTS: Comparing the two educational
      approaches during four conferences, 221 HMS talks and 103 symposia were
      presented. The HMS course covered a wide range with 133 topics; the symposia
      focused on 30 topics, most of which were linked to recently approved new
      therapeutic products manufactured by the funders. Both the course and the
      symposia were highly rated by attendees. DISCUSSION: When CME presentations for
      primary care physicians receive direct support from industry, the range of
      offered topics is narrower than when programs are developed independently of such
      support. There appear to be no differences in the perceived quality of
      presentations delivered with and without such support. Our experience suggests
      that a firewall between program planners and providers of financial support will
      result in a broader array of educational subjects relevant to the field of
      primary care.

PMID- 12004641
TI  - Medical education and communication companies: an updated in-depth profile.
AB  - INTRODUCTION: The integrity of medical education and communication companies
      (MECCs) and their role in continuing medical education (CME) are frequently
      challenged, perhaps because of a lack of published information characterizing
      these providers. Published in 1998, a survey of MECCs began the identification
      and description of these organizations so that meaningful conclusions could be
      drawn about their role in CME. The present study enhances the profile created by
      that original survey. METHODS: A 21-item questionnaire was mailed to 182
      companies identified from 3 commercially available lists. RESULTS: Forty-six
      (25.2%) companies responded. Surveys revealed that 25 (54%) of the respondent
      companies have 1 to 25 employees, 66.6% have separate CME divisions, 64.4% are
      accredited to provide CME, 77.7% have at least 1 licensed health care
      professional on staff, and 33.2% of their leaders hold a doctoral degree and
      28.8% hold professional licensure, whereas 88.6% have advisory boards, 93.1% of
      which review each CME activity. DISCUSSION: MECCs comprise a diverse group
      differing in size and accreditation status. They contribute to the CME community
      by providing a variety of services, with highly trained staff. Future studies of
      CME providers should continue to expand the base of knowledge regarding these
      organizations, resulting in better understanding among all types of providers,
      opportunities for collaboration, and, ultimately, education that improves patient
      care.

PMID- 12004642
TI  - Immunocytochemical and RT-PCR analysis of connexin36 in cultures of mammalian
      glial cells.
AB  - The expression of connexin36 (Cx36) was studied in primary cultures of rat brain
      glial cells: mature astrocytes, ameboid and ramified microglia and immature
      oligodendrocytes (at middle period of myelinogenesis). The data from these cells
      were compared with those obtained from cultures of neocortical and hypothalamic
      neurons. mRNA encoding Cx36 was investigated by RT-PCR, the Cx36 protein by
      immunocytochemistry using a polyclonal antibody against Cx36 in cells
      characterized by antibodies specific for the single cell types. The Cx36 was
      found in oligodendrocytes, both ameboid and ramified microglial cells and in
      neurons. Astrocytes showed no detectable expression of the Cx36. The expression
      of Cx36 in oligodendrocytes and microglial cells suggests an involvement of the
      direct cell-cell communication channels formed by Cx36 in myelin formation and in
      brain development, damage and repair processes.

PMID- 12004643
TI  - Dream contents and failing memories.
AB  - Mentation during sleep states is thought to originate in an activation of brain
      circuits that encode inherited and experiential memories. Spontaneous degradation
      of the strengths of synapses occurs in all brain circuits because of "turnover"
      of molecules essential for synaptic function. In circuits employed frequently
      during waking, synaptic strengths are refreshed and maintained in their dedicated
      or functional ranges largely through use, by virtue of activity-dependent
      synaptic plasticity. In circuits employed infrequently during waking, synaptic
      strengths are refreshed largely during sleep, by circuit activations induced by
      spontaneous, self-generated, largely low-frequency brain waves, also by virtue of
      activity-dependent synaptic plasticity. The outputs of circuits activated during
      sleep do not necessarily rise to the level of 'unconscious' awareness. Such an
      absence of awareness of the outputs of individual circuits, that is, an absence
      of dreaming, is proposed to be the primitive condition in animals that sleep. On
      the other hand, temporal binding of these outputs is accompanied by the thoughts
      and perceptions of dreams, which is proposed to be the advanced condition.
      Linking or serial ordering of otherwise 'static' thoughts and perceptions gives
      rise to continuous, often narrative and veridical, dreams. In all cases, dream
      contents are derived from the memories--not necessarily veridical--encoded in the
      reinforced circuitry. In the absence of synaptic strength refreshments during
      sleep, synaptic strengths in infrequently used circuits would weaken and the
      circuits would become incompetent, with their encoded memories degraded or lost.
      Maintenance of synaptic strengths in infrequently used circuitry during sleep
      apparently does not always achieve perfection. Weakened synapses begin to occur
      in circuits in appreciable numbers in children after the age of about 5 years.
      When these 'incompetent' circuits (with weakened synapses) are activated during
      sleep, there are minimal influences on dream contents, namely, distortions that
      make some objects, such as animals, faces, and scenes, unrecognizable. As
      weakened synapses increase in numbers with age, the numbers of distorted objects
      in dreams also increase. In adults, people in as many as 80% of dreams may be
      unrecognizable. Besides the normal weakening of synaptic strengths, some synapses
      become defective, in consequence of deleterious, adventitious, exogenous
      influences, for example, radiation. As these faulty synapses accumulate in old
      memories, activation of circuits incorporating them during sleep leads to dreams
      with incoherent, bizarre, or impossible contents. The infrequent activation of
      such old, incompetent circuits in some waking conditions leads to false memories,
      delusions, or hallucinations.

PMID- 12004644
TI  - Pineal gland hormone and idiopathic scoliosis: possible effect of melatonin on
      sleep-related postural mechanisms.
AB  - Experimental and clinical evidences indicate that endocrine mechanisms,
      particularly involving the pineal gland, exert a role in the development of
      postural deficits leading to the occurrence of idiopatic scoliosis (IS). In
      particular, experiments performed in bipedal animals have shown that removal of
      the pineal gland, which secretes melatonin (M), induced a scoliosis, and that in
      such preparations, administration of this hormone prevented the development of
      this deformity (cf. 131). It appears also that adolescents with IS showed a
      reduced level of serum M with respect to age-related control subjects. The
      possible mechanisms involved in the M regulation of the tonic contraction of the
      axial musculature have been discussed. It is known that the pineal gland is
      implicated in the control of circadian rhythms, including the sleep-waking cycle,
      and that during this cycle there are prominent changes in postural activity,
      which affect not only the limbs, but also the axial musculature. These changes
      are characterized by a decrease followed by a suppression of postural activity,
      which occur particularly during transition from wakefulness to synchronized sleep
      and, more prominently, to rapid eye movement (REM) sleep. Episodes of postural
      atonia may also occur during the cataplectic episodes, which are typical of
      narcolepsy. Cholinergic and/or cholinoceptive neurons located in the dorsal
      pontine reticular formation (pRF) and the related medullary inhibitory
      reticulospinal (RS) system, intervene in the suppression of posture during REM
      sleep, as well as during the cataplectic episodes which occur in narcolepsy.
      These structures are under the modulatory (inhibitory) influence of the
      dorsomedial and the dorsolateral pontine tegmentum, where serotoninergic raphe
      nuclei (RN) neurons and noradrenergic locus coeruleus (LC) neurons are located.
      We postulated that M may act not only on the circadian pacemaker, but also
      directly on the pontine tegmental structures involved in the regulation of
      posture during the animal states indicated above. This hypothesis is supported by
      the facts that: 1) the dorsal pRF may contain specific binding sites for M; 2)
      this structure is particularly sensitive to M in adolescents, as well as in adult
      subjects affected by narcoleptic disturbances leading to cataplexy; 3) M
      increases the release of serotonin (5-HT), a neurotransmitter which enhances the
      postural tone by acting on the dorsal pRF: on the other hand, deficits in M
      levels may lower the activity of the serotoninergic raphe system, thus leading to
      a decrease or suppression of postural activity similar to that occurring either
      during REM sleep or during the cataplectic episodes typical of narcoleptic
      patients; 4) IS patients may show episodes of sleep apnea, a phenomenon which has
      been attibuted to a reduced tonic contraction of primary and accessory
      respiratory muscles during REM, resulting from a reduced release of 5-HT at
      dorsal pontine level. It has been postulated that, if the reduced M and 5-HT
      levels are subliminal to produce a complete suppression of posture under the
      conditions reported above, the reduced postural tone, which results from this
      condition may lead to the development of IS, due to hypotonia which affects the
      axial musculature. M secretion could be regulated not only by the activity of the
      serotoninergic raphe neurons projecting to the pineal gland, but probably also by
      the activity of noradrenergic LC neurons. It is likely that the development of
      IS, which results from a reduced level of M and 5-HT, may occur provided that the
      noradrenergic LC inhibition of the pontine structures is impaired. Such
      impairment could depend upon genetic factors, similar to those postulated to play
      a role in narcolepsy. In conclusion, the possibility exists that an impaired
      activity of brain monoaminergic systems may lead to disfunction in the production
      of M, which is apparently an important factor in the etiopathogenesis of IS.

PMID- 12004645
TI  - Developmental expression of nerve growth factor in the eye of rats affected by
      inherited retinopathy: correlative aspects with retinal structural degeneration.
AB  - We have previously reported that exogenous administration of nerve growth factor
      (NGF) in C3H/HeJ mouse strain affected by retinitis pigmentosa (RP) delayed
      retinal degeneration, suggesting that NGF may be implicated in retinal
      development. Whether NGF is present in the developing eye was not investigated.
      To address this question we have used Royal College of Surgeons (RCS) rats,
      characterised by photoreceptor loss during postnatal life. The results of these
      studies showed that while the thickness of the outer nuclear layer (ONL) of RCS
      is comparable to controls, while the amount of NGF expressed in the eye of this
      mutant rat is significant lower, as compared to control eye. This observation
      suggests that the lower presence of NGF in the eye of RCS rats during early
      postnatal life might be one critical key factor implicated in RP. The results of
      these studies will be presented and discussed.

PMID- 12004646
TI  - Effect of K, MG aspartate on some biological parameters of aging rats.
AB  - The effect of K and Mg salts of aspartic acid (Cardilan) on the serum
      concentration of selected proteins and phagocytic activity in aging male Wistar
      rats was investigated. Cardilan was administered in tap water for 7 days a month
      for 3 months before the last observed interval (12, 18 and 24 month). In a part
      of animals, the aging process was accelerated by sublethally gamma-irradiation.
      The administration of Cardilan slowed down the changes in the concentration of
      prealbumin, albumin, haptoglobin, haemopexin, C3 complement in non-irradiated
      rats (DC). This effect was extended to the changes in transferrin level in
      irradiated rats (IDC). The phagocytic activity in both DC, IDC rats was lower
      compared with controls drinking water (DW, IDW), but not significantly. The
      effect of Cardilan administration appears to be the greatest in 24-month-old
      rats, when the treated animals survived better by 25% in IDC group and by 26%
      better in DC rats, compared with those of the same age controls. Potassium and
      magnesium salts of aspartates are suitable compounds for life prolongation in the
      experimental conditions.

PMID- 12004647
TI  - Is there a future for middle managers in nursing in the changing health care
      system?

PMID- 12004648
TI  - Reinventing middle managers in nursing for a future in the changing health care
      system.

PMID- 12004649
TI  - Carrying on the legacy of Lillian Wald. Partnership with the Henry Street
      Settlement and the Lienhard School of Nursing at Pace University.
AB  - The Lienhard School of Nursing (LSN) at Pace University and the Henry Street
      Settlement (HSS) developed a partnership to bring nursing back to the HSS founded
      by nursing leader, Lillian Wald. Through this partnership HSS and LSN faculty and
      students explored how they could accomplish the goal of providing nursing care to
      a diverse urban population. Struggles to understand the community and the role of
      nursing in this kind of setting provided students with unique and complex
      community and leadership experiences. Students learned not only from the nursing
      care they provided but also from the behaviors of the stakeholders in the
      partnership. The partnership has provided an ongoing opportunity for continuing
      the legacy of Lillian Wald.

PMID- 12004650
TI  - Creating an education and research consortium. Framework and development.
AB  - Today's schools of nursing and clinical organizations providing nursing care need
      to synchronize their efforts to maximize one another's achievements. This article
      describes how complementary goals of two or more organizations can be achieved
      through mutual efforts, and briefly details the process of consortium development
      and the role of leaders in this process. Interorganizational collaboration
      examples are discussed at two institutions in two different regions of the
      country, and the authors offer a number of ways that nursing education and
      practice can work together to meet their overlapping needs, attack the nursing
      shortage, and move nursing education and practice toward evidence-based care.

PMID- 12004651
TI  - Heroism. A core value of the Army Nurse Corps.
AB  - Celebrating the 100th Anniversary of the Army Nurse Corps, this article describes
      the heroic acts of a number of Army nurses. Beginning with the Civil War and
      concluding with the Vietnam War, examples are given of nurses who were not afraid
      to take risks to serve the United States of America and its soldiers. Examples
      portray the steadfast, bold, ethical, caring, and brave behaviors of these nurses
      as they took the lead on behalf of their patients and other nurses and soldiers.

PMID- 12004652
TI  - Providing care to all.

PMID- 12004653
TI  - Pathways to saving lives.

PMID- 12004654
TI  - Artificial saliva products and drugs to treat xerostomia.

PMID- 12004655
TI  - Treatment recommendations: "doctor knows best".
AB  - Patients often develop an abiding trust in their health care providers and may
      agree with any recommendations that a dentist offers. This level of trust is a
      compliment to the dentist and the profession. However, patients who request that
      a doctor perform the treatment that he or she feels is best and who prefer to
      avoid an informed consent process must be educated as to the role of informed
      consent and their part in the process. Even when a patient is adamant in refusing
      information about his or her condition or states a clear reason as to why he or
      she does not desire to know a diagnosis or treatment plan (for example, dental
      phobia or fear of cancer), the dentist has an ethical and legal obligation to
      work with an appropriate surrogate of the patient's choice and make reasonable
      attempts at including the patient in the discussion. These patients should be
      offered the option of discussing the diagnosis and treatment alternatives with a
      family member or friend present and may include such a surrogate in the informed
      consent process. When patients clearly lack capacity to consent, the process of
      informed consent will revert automatically to appropriate surrogates. Finally,
      patients from different cultures may bring a new set of considerations to the
      process of informed consent and may require that a modification of the Western
      tradition be considered, allowing a significant role for the family of the
      patient in making treatment decisions.

PMID- 12004656
TI  - Issues in handling impression materials.
AB  - Implant restorations require extreme accuracy since the implants are rigidly
      fixed. Although impression materials can be highly accurate, small inaccuracies
      are acceptable because the periodontal ligament allows for tooth movement. This
      luxury is not available with implants. A problem is the rotation of direct
      impression copings and distortion of interabutment positions in the master cast.
      Wee investigated the amount of torque required to displace a coping in eight
      impression material groups and the positional accuracy of the materials. The
      initial examination of torque narrowed the acceptable materials to a medium
      viscosity polyether, a high viscosity addition silicone, and a medium viscosity
      polysulfide-condensation silicones were eliminated. The results showed that the
      polyether and addition silicone produced casts with minimal distortion. Finally,
      it always is prudent to read the manufacturer's recommendations for use of
      impression materials. Catalyst-to-base ratios vary, as do working and setting
      times, depending on exact compositions. Impression materials also have various
      degrees of compatibility with stone, particularly the hydrocolloids, and it is
      advisable to use the recommended stone. Adhesives should be applied at least 15
      minutes prior to loading the impression material. If at all possible, use of a
      rigid tray is recommended and impressions should be poured in the dental office;
      this minimizes the error produced at the beginning of the fabrication process.
      Elimination of errors early in fabrication of a prosthesis help prevent their
      magnification and result in a better-fitting restoration, requiring minimal
      adjustment in the end.

PMID- 12004657
TI  - Erosions of oral and conjunctival mucosa. Mucous membrane pemphigoid.

PMID- 12004658
TI  - Failure of eruption. Adenomatoid odontogenic tumor.

PMID- 12004659
TI  - Preventing and treating the oral complications of cancer therapy.
AB  - Approximately 1.25 million Americans are diagnosed with cancer for the first time
      each year. Forty percent (500,000) of these individuals develop oral
      complications to their cancer therapy. The three modalities of cancer therapy
      (surgical, pharmacologic, or radiotherapy), employed individually or, more often,
      in combination, may result in a variety of general and/or treatment-specific oral
      complications. In many cases, these oral complications lead to dose reductions,
      delays, or termination of cancer treatment, which reduce the chances of remission
      or cure. This paper reviews the basic concepts of pretreatment oral care,
      treatment of oral complications during cancer therapy, and the need for
      continuing posttreatment oral care.

PMID- 12004660
TI  - Screening for oral cancer and precancer--a valuable new technique.
AB  - Many precancerous or cancerous oral lesions may resemble benign lesions and a
      definitive diagnosis on clinical grounds alone may be difficult, if not
      impossible, to make. The introduction of OralCDx, an oral brush biopsy procedure,
      permits the dental practitioner to determine which lesions contain atypical or
      dysplastic epithelial cells and require that a conventional scalpel biopsy be
      performed. This article reviews the features of the test, explains the clinical
      situations for which its use is recommended, and discusses the interpretation and
      significance of the biopsy reports.

PMID- 12004661
TI  - Accessory innervation of the mandible: identification and anesthesia options.
AB  - The nerves commonly associated with accessory innervation of the mandible are
      identified and alternative techniques to gain their anesthesia are recommended,
      based on sound anesthetic principles and the current understanding of nerve
      anatomy.

PMID- 12004662
TI  - Recent advances in the treatment of viral hepatitis.
AB  - The viral hepatitis viruses and the diseases they cause are presented in terms of
      their importance to the practice of dentistry. Each virus will be discussed in
      terms of its epidemiology, risk of transmission in dentistry, and steps that can
      be taken to avoid transmission. The scope of this review emphasizes publications
      from 1996-1999.

PMID- 12004663
TI  - A practical approach to improving the quality of water used for routine dental
      treatments.
AB  - The water delivered through dental units connected to municipal water supplies
      often is contaminated with bacteria and other organisms as a result of biofilm
      formation in waterlines. Water and other solutions used for dental treatment
      should meet generally recognized standards for drinking water quality. Public
      concern over the safety of drinking water and media attention paid to dental
      water quality will continue to increase. The number of immunocompromised patients
      who are at risk of developing infectious diseases from exposure to contaminated
      water aerosolized from dental units also will continue to increase. Improving the
      quality of water used in routine dental treatment is a worthwhile goal and
      reasonable measures to improve water quality now are available.

PMID- 12004664
TI  - Understanding and evaluating the endodontic file.
AB  - One of the most significant advancements in the field of endodontics has been the
      change in the endodontic file. The new files have different metallurgy, taper,
      cutting efficiency, and rotary capabilities. This article reviews and updates the
      advancements in endodontic instrumentation.

PMID- 12004665
TI  - In vitro efficacy of a one-bottle adhesive system with three restorative
      materials.
AB  - The shear bond strength to dentin of a new single-bottle adhesive with three
      restorative materials (composite resin, compomer, and amalgam) was evaluated. The
      results were statistically different (ANOVA, p < 0.05). Groups 1 and 2 were not
      significantly different from each other, but both were statistically higher than
      Group 3. The fracture mode was not related to the shear bond strength values.

PMID- 12004666
TI  - Restoration and reinforcement of endodontically treated teeth with a polyethylene
      ribbon and prefabricated fiberglass post.
AB  - In the past it was considered appropriate to place a cast post and core in every
      pulpless tooth without regard to the remaining supportive tooth structure
      present. Recent research and the advent of adhesive bonding techniques have
      caused clinicians to reevaluate their restorative protocol. This article reviews
      the current literature with regard to restoration of the endodontically treated
      tooth and presents a method for restoration and reinforcement utilizing a
      combination of polyethylene ribbon and a prefabricated fiberglass post.

PMID- 12004667
TI  - Proliferative verrucous leukoplakia: a case report.
AB  - Proliferative verrucous leukoplakia (PVL) is a particularly aggressive form of
      oral leukoplakia that is resistant to treatment and presents a high risk of
      recurrence and malignant transformation. This article describes the microscopic
      and clinical characteristics of one case of PVL, which initially presented as
      hyperkeratosis with mild dysplasia and posteriorly developed multifocal areas and
      verrucous carcinoma despite treatment.

PMID- 12004668
TI  - In vitro microleakage study of a condensable and flowable composite resin.
AB  - The aim of this study was to evaluate the in vitro microleakage of a condensable
      composite resin recommended for Class II restorations with and without a flowable
      composite resin as a liner. There were statistically significant differences
      between all groups and between individual groups (p < 0.05). The results showed
      significantly less microleakage in teeth restored with flowable composite resin
      underneath a condensable composite resin.

PMID- 12004669
TI  - Peripheral giant cell granuloma: a case report.
AB  - The peripheral giant cell granuloma is a reactive lesion of the soft tissue of
      the oral cavity. Clinical appearance ranges from normal tissue coloration to dark
      red or purplish. These are elevated lesions generally 5-15 mm in diameter.
      Etiology is considered to be chronic irritation. To decrease the risk of clinical
      recurrence, treatment is complete excision to include the underlying periosteum.
      Histologic features of the peripheral giant cell granuloma include multinucleated
      giant cells with a stroma that may contain osteoblasts, myofibroblasts,
      macrophages, and Langerhans cells. A case report is presented.

PMID- 12004670
TI  - Drugs and dry mouth.

PMID- 12004671
TI  - Cosmetic treatment, autonomy, and risks: "if you don't do it, I'll go to a
      dentist who will".
AB  - Patient requests and treatment goals may exceed the limits of professional
      practice and may have an adverse effect on health. When doctors encounter these
      types of requests, they first must decide whether the patient has the capacity to
      consent to such care. In the case of child patients, no such capacity exists and
      surrogate consent to care must be, in the opinion of the doctor, in the child's
      best interests. Parents who request potentially harmful procedures for a child
      with no hope for any health care benefit should be refused politely. Adult
      patients who request harmful elective procedures for themselves also should be
      educated and helped to fully understand why the request represents substandard
      treatment. The long-term consequences of these requests must be detailed clearly
      for these patients. Elective cosmetic treatment that will lead to long-term
      adverse effects on function and health raises serious ethical concerns in which
      the principle of nonmaleficence likely will trump the patient's autonomy.

PMID- 12004672
TI  - Surgical templates for function and esthetics in dental implants.
AB  - The functional and esthetic importance of surgical templates associated with
      dental implants has been discussed. The design of the stent and proposed location
      of the fixtures basically determine the dentist's "wish list." Although ideal
      placement of an implant fixture often is achieved, it can be aided through use of
      a surgical template. Particularly useful in larger partially edentulous cases as
      described above, the ideal template is made of hard acrylic with holes slightly
      larger than the 3.0 mm drill often used during surgery. Construction of a
      template requires the dentist and surgeon to think about the case, create a wax
      up, and decide on location before constructing the appliance. This process will
      benefit all, particularly the patient, and provide a foundation for a long
      lasting prosthetic result.

PMID- 12004673
TI  - Mucosal pigmentation. Nevus.

PMID- 12004674
TI  - Yellow nodule of floor of mouth. Lymphoepithelial cyst.

PMID- 12004675
TI  - The importance of dental implants.
AB  - Implant dentistry has evolved into the mainstream of restorative practices all
      over the world. Maintenance of bone after tooth loss to improve or maintain
      facial esthetics and improved retention, function, and performance of removable
      restorations are only some of the advantages for the edentulous patient. No
      longer are implants considered only when traditional restorations cannot be
      fabricated. Evidence-based reports indicate implant restorations last longer than
      those on teeth and the abutment teeth are at less risk of loss or complication.

PMID- 12004676
TI  - Using transitional implants during the healing phase of implant reconstruction.
AB  - The use of dental implants to reconstruct the fully and partially edentulous jaw
      has been well-documented in the literature. Simplification of the healing phase
      with transitional implants is becoming a routine step in the management of the
      integration period for the patient undergoing implant reconstruction. Restoration
      and maintenance of vertical dimension with transitional implants in conjunction
      with implant surgical therapy is an effective method to provide the patient with
      an immediate and comfortable transitional appliance. This approach facilitates
      the uneventful reconstruction with the definitive prosthesis.

PMID- 12004677
TI  - Predictable maxillary central incisor reconstruction: surgical and prosthetic
      case report.
AB  - Replacing a maxillary incisor is a challenge from both a functional and esthetic
      standpoint. Techniques that strive to return the site to be reconstructed to its
      optimal state, thereby mimicking the natural dentition, must be employed. This
      case report serves to outline the steps necessary to reconstruct a commonly
      encountered maxillary prosthetic challenge. With a combination of surgical and
      prosthetic steps, an optimal prosthetic result can be achieved. This cooperation
      between general dentist, surgeon, and laboratory technician will serve to provide
      predictable and long-lasting return to a near-normal anatomic state, thereby
      offering our patients the highest level of care for prosthetic replacement.

PMID- 12004678
TI  - Accessing restoration margins--a multidisciplinary approach.
AB  - The problem of paresthesia after dental procedures has existed for years. The
      literature presents several simple precautions dentists can take to avoid
      paresthesia caused by injection in nonsurgical cases. Although the risks of
      complications are still extremely small (1:785,000), there has been an increase
      recently in the number of cases reported. Though not all instances cause total
      paresthesia, these incidents do involve prolonged numbness, which is of concern
      to both the patient and practitioner.

PMID- 12004679
TI  - Submerged permanent teeth: literature review and case report.
AB  - Submerged permanent teeth pose a diagnostic as well as a treatment planning
      dilemma. Teeth with delayed eruption, arrested eruption, and paradoxical movement
      all can appear to be submerged teeth. While orthodontics may seem like the
      simplest solution, it often has the most frustrating results. A multidisciplinary
      approach often is required, utilizing surgical, orthodontic, and prosthetic
      components.

PMID- 12004680
TI  - A comprehensive review of oral cancer.
AB  - Oral squamous cell carcinomas comprise 2-3% of all new malignancies diagnosed in
      the United States, making it the 10th most common malignancy. However, for the
      last few decades, the average five-year survival rate of 50% has not changed
      significantly. This article reviews the risk factors associated with the
      development of oral cancer and how premalignant (leukoplakia and erythroplakia)
      and actual cancerous lesions may appear. Diagnostic tools and aids to diagnosis
      are discussed, as are treatment modalities. It is imperative that all dental
      professionals perform a simple head and neck examination in addition to an oral
      examination during each new patient visit and each six-month recall appointment.
      Early detection saves lives.

PMID- 12004681
TI  - Sharing responsibility.

PMID- 12004682
TI  - Site-specific chlorhexidine: a periodontal alternative.
AB  - Three case reports demonstrate the clinical use of an adjunctive chlorhexidine
      chip capable of sustaining local antimicrobial activity for 7-10 days. The chip
      is easy to place, requires no additional chair time for removal, is self
      adherent, and can be provided to periodontal maintenance patients on a recurring
      basis. This is another adjunct that can be part of the clinician's armamentarium
      when presented with a clinically challenging localized periodontal defect.

PMID- 12004683
TI  - Effects of sonic toothbrush use on permanent dental luting cements.
AB  - The aim of this project was to assess the effects of sonic toothbrushes on
      commonly used permanent luting cements. While results showed differences between
      the tensile bond strengths of the three cements, the differences were similar
      between the two groups: sonic and nonsonic toohbrush exposure. These findings
      suggest that the sonic toothbrush had no significant effect on the tensile bond
      strengths of any of the three tested cements.

PMID- 12004684
TI  - Treatment of gingival recession with collagen membranes.
AB  - Periodontal plastic surgical techniques to obtain root coverage traditionally
      have utilized autogenous soft tissue grafts. Guided tissue regeneration (GTR)
      increasingly is being used as an alternative to soft tissue grafting in
      attempting root coverage. Resorbable membranes in GTR therapy prevent the need
      for a second surgery to harvest donor tissue. GTR membranes composed of collagen
      are effective barriers that add to the thickness of the overlying gingiva and
      possess platelet-aggregating properties that may help in early wound healing. The
      cases presented here demonstrate the treatment of gingival recession with a
      resorbable collagen membrane.

PMID- 12004685
TI  - The Americans with Disabilities Act--a new perspective.

PMID- 12004686
TI  - Esthetic dentistry.

PMID- 12004687
TI  - Treatment planning.

PMID- 12004688
TI  - Narcotic analgesics for dental pain: available products, strengths, and
      formulations.

PMID- 12004689
TI  - Virtue versus ethical obligations: working for system-wide change.
AB  - Clinical ethics issues most often focus on the individual encounter or
      relationship between a specific doctor and patient. This is an appropriate focus,
      since this dynamic defines the normal course of health care delivery and it is
      within this relationship that most ethical dilemmas arise. Once a provider has
      discharged his or her ethical duties to a particular patient, further efforts
      toward assisting that patient or toward social policy affecting health care in
      general are virtuous but are not ethical mandates. Issues of distributive justice
      in health care allocation and reimbursement are examples of policy issues that
      impact persons who may not be patients in one's practice but who may benefit from
      the actions of the dental profession. Many times, as in the case presented, the
      dentist's awareness of such issues of distributive injustice may arise from an
      individual patient encounter. In the process of attempting to secure justice for
      a particular patient, the dentist may become aware of the broader social context
      of the problem. This awareness calls upon dentists, just as it calls upon other
      health care providers, to become involved via their professional organization and
      to work for distributive justice. While individual values may mediate the duty to
      advocate for many social issues, professional values that are oriented toward
      improving the health and well-being of all in a society require organized health
      care professions to advance these causes.

PMID- 12004690
TI  - Preparation of teeth for esthetic restorations.
AB  - Preparation details have been described for a porcelain veneer restoration on the
      most commonly used teeth. With operator knowledge of the preparation, sharp
      instrumentation, and, most of all, patience, it is possible to place a
      restoration that may last as long as any others outside of those made of cast or
      direct gold. It is imperative to remember that this type of conservative
      "esthetic" dentistry should be performed only on canine-guided occlusions after
      equilibration (if necessary) (Fig. 13). Even then, it still is possible to
      fracture a veneer accidentally (Fig. 14). Prior to beginning treatment, it is
      prudent to inform the patient of the pros and cons of using porcelain veneers,
      including a warning of possible failure.

PMID- 12004691
TI  - Palatal ulcer. Major aphthous ulcer.

PMID- 12004692
TI  - Oral and cutaneous lesions. Erythema multiforme.

PMID- 12004693
TI  - Differential diagnosis of two disorders that produce common orofacial pain
      symptoms.
AB  - Severe orofacial pain often is diagnosed as trigeminal neuralgia, with little
      distinction made as to which type--typical or atypical. In addition,
      osteonecrosis of the jaws quite often produces symptoms which mimic trigeminal
      neuralgia. Unless diagnosed correctly, a patient suffering from a condition of
      "dead bone" may be referred for unnecessary neurosurgery. The general dentist
      often is the one doctor who can make the proper diagnosis and guide the patient
      toward the proper treatment.

PMID- 12004694
TI  - Pseudo-dental pain and sensitivity to percussion.
AB  - Two case reports examine a little-known cause of dental pain and sensitivity to
      percussion. Contrary to the traditional assumption that pain and sensitivity to
      percussion almost always are diagnostic of pulpal inflammation and/or necrosis,
      these symptoms actually may be referred to the sensitive tooth from trigger
      points in the masticatory muscles. Therefore, myofascial pain syndrome must be
      ruled out in patients who have dental pain and display sensitivity to percussion.

PMID- 12004695
TI  - Musculoskeletal pain: prevalence, prevention, and differences among dental office
      personnel.
AB  - Data regarding the presence and specific region of musculoskeletal pain were
      collected as part of a study that surveyed more than 5,000 dental personnel,
      dentists, and dental auxiliaries. The magnitude of the overall study, which
      included all types of dental professionals, made possible identification of the
      prevalence of musculoskeletal pain and comparison of regions of pain among the
      different dental professionals.

PMID- 12004696
TI  - Pain perception and utility: a comparison of the syringe and computerized local
      injection techniques.
AB  - Thirty patients received maxillary infiltration and mandibular inferior alveolar
      nerve block injections with both a traditional syringe and a computerized system,
      the Wand. Patients noted their preference for either system and rated their
      injection pain and postoperative discomfort on a ten-point scale for each type of
      injection. Mean injection discomfort ratings with the Wand were lower than with
      the syringe but were not statistically significant. Reduced postoperative
      discomfort using the Wand for the inferior alveolar nerve block was significant.
      Both of the dentists in the study and those patients who stated a preference
      favored the Wand system.

PMID- 12004697
TI  - Painless pediatric local anesthesia.
AB  - This clinical report presents a technique for painless palatal/lingual
      infiltrations for pediatric patients. When treating a young child, pain control
      is very important in order to gain the patient's cooperation. Procedures such as
      clamp placement, operative techniques, pulp therapy, and extractions cause
      discomfort, some more than others, requiring profound anesthesia. However,
      achieving profound anesthesia painlessly in the palatal and lingual aspects is
      difficult.

PMID- 12004698
TI  - Neuritic toothache.
AB  - Diagnosing and managing neuropathic pain with associated sensory aberrations can
      be aggravating and frustrating for both the dentist and the patient. The teeth
      and intraoral and extraoral tissues can be affected if neuritis is located in the
      maxillary or mandibular nerve branches. Dentists should be aware of a neuritic
      etiology for tooth pain because an incorrect diagnosis can lead to ineffective
      and unnecessary dental work.

PMID- 12004699
TI  - Enigmatic pain referred to the teeth and jaws.
AB  - A number of obscure syndromes can mimic dental or jaw pain in the absence of
      pathosis within these structures. This enigmatic dental pain includes conditions
      such as pretrigeminal neuralgia, complex regional pain syndrome, temporal
      tendinitis, and carotodynia. Each of these syndromes is described through a
      pertinent case report to illustrate appropriate diagnosis and treatment.

PMID- 12004700
TI  - Diagnostic utility of thermal printed panographs compared with corresponding
      computer monitor images.
AB  - Digital panoramic radiographs may be viewed with computer monitors or archived as
      thermal or laser prints. To compare the available diagnostic information from
      thermal print images to that of corresponding computer monitor images, four
      calibrated evaluators performed a qualitative analysis of 13 specified anatomic
      features in 60 pairs of digital panoramic images presented in random order on a
      computer monitor and as thermal printed images. Each anatomic site was rated both
      for subjective diagnostic quality and diagnostic utility using a nominal scale.
      Computer monitor images more often were subjectively judged to have better
      quality. Within the parameters of this study, both formats had acceptable
      diagnostic utility for the majority of the anatomic features evaluated.

PMID- 12004701
TI  - Comparison of the cutting efficiencies of electric motor and air turbine dental
      handpieces.
AB  - As part of a larger comprehensive performance evaluation to determine whether
      electric motor handpieces are a suitable substitute for air turbine handpieces in
      a portable field dental treatment and operating system, the cutting efficiencies
      of electric motor and air turbine handpieces were compared. A device was made
      that applies an identical cutting force to a glass ceramic material for each
      handpiece tested. The laboratory results show that with equal amounts of applied
      force, the electric motor handpiece cuts a glass ceramic material significantly
      more efficiently (volume of material removed per second) than does the air
      turbine. In clinical trials, after minimal experience utilizing the electric
      motor, the majority of dentists felt that the electric motor cut tooth and
      amalgam more efficiently than did the air turbine.

PMID- 12004702
TI  - Diascopy: a clinical technique for the diagnosis of vascular lesions.
AB  - Dentists can quickly determine the vascular nature of many intraoral lesions by
      applying a clinical test for blanchability. Such a clinical test is called a
      diascopy. Described here are the circumstances in which diascopy can be used in a
      dental practice and what useful information is provided by performing diascopy on
      oral mucosal lesions.

PMID- 12004703
TI  - Bar overdentures utilizing the Locator attachment.
AB  - Implant-retained overdentures are a restorative option for both the fully and
      partially edentulous arches. A new attachment, the Locator, which features a
      reduced interarch requirement and the advantage of built-in guide planes
      providing precise insertion, is described. The Locator is an advancement in
      attachment technology, with an improved design combined from the best features of
      a ball attachment, an ERA attachment, and a cap attachment.

PMID- 12004704
TI  - Single-appointment crown lengthening and restorative procedure under the rubber
      dam.
AB  - A one-stage approach to performing crown lengthening and restorative procedures
      under a rubber dam is described with case reports.

PMID- 12004705
TI  - Fluoride: after 50 years, a clearer picture of its mechanism.

PMID- 12004706
TI  - The dentist as Robin Hood?

PMID- 12004707
TI  - Alveolar distraction osteogenesis: a case report involving ankylosed maxillary
      central incisors.
AB  - Restorative dentistry, for the optimal esthetic and functional result, at times
      requires innovation, exacting techniques, and employment of various treatment
      modalities. A case has been presented here involving a large esthetic defect in
      the maxillary anterior. Traditional methods of restoration may have been
      successful but alveolar distraction osteogenesis was determined to be the
      treatment of choice due to time, predictability, lack of invasiveness, and cost.
      It is a relatively new surgical procedure that has many applications to restore
      esthetic defects, ridge augmentation, and large craniofacial abnormalities.
      Movement of osseous sections can be made in a vertical, labial, or lingual
      direction. When treatment planning restorative dentistry with vertical hard and
      soft tissue deficiencies, alveolar distraction osteogenesis can be considered to
      achieve optimal esthetics and a more ideal crown-to-root ratio. Further
      information can be obtained from any oral surgeon, orthodontist, or from the
      Internet. Dr. Martin Chin, a maxillofacial surgeon from San Francisco, has done
      much of the clinical work regarding distraction procedures on humans and
      continues to be an innovator in craniofacial distraction osteogenesis. His work
      can be found on the Internet at www.distraction.net; other interesting Web sites
      include www.klsmartin.com/distract.dir/indexdistract.html and www.seattle
      implants.com/articles/distost.htm.

PMID- 12004708
TI  - Chemoprevention of oral cancer by green tea.
AB  - Green tea has been a popular beverage for many centuries. Only recently, however,
      has the anti-cancer power of green tea constituents been unveiled. Green tea
      polyphenols are found to induce apoptosis (programmed cell death) in many types
      of tumor cells, including oral cancer cells. However, mechanisms that enable
      normal cells to evade the apoptotic effect still are not understood. In this
      study, cell growth and invasion assays combined with apoptosis assays were used
      to examine the effects of green tea extracts, green tea polyphenols, and the most
      potent green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on normal
      human keratinocytes and oral carcinoma cells. The results showed that green tea
      and its constituents selectively induce apoptosis only in oral carcinoma cells,
      while EGCG was able to inhibit the growth and invasion of oral carcinoma cells.
      These differential responses to green tea and its constituents between normal and
      malignant cells were correlated with the induction of p57, a cell cycle
      regulator. These data suggest that the chemopreventive effects of green tea
      polyphenols may involve a p57 mediated survival pathway in normal epithelial
      cells, while oral carcinoma cells undergo an apoptotic pathway. Therefore,
      regular consumption of green tea could be beneficial in the prevention of oral
      cancer.

PMID- 12004709
TI  - The first dental visit.
AB  - The recommended age for the first dental visit seems to vary among and within the
      professions. Unfortunately, the first visit often is prompted by clinical caries
      or dental trauma. The purpose of this paper is to provide guidelines for
      examining the toddler and information to be offered to parents during the
      consultation. Early identification and intervention for children with high caries
      risk, education of other health professionals and parents with preventive
      strategies, and the establishment of a relationship with a dentist prior to a
      traumatic injury should be mutual goals.

PMID- 12004710
TI  - Recurrent aphthous stomatitis: etiology, diagnosis, and treatment.
AB  - Recurrent aphthous stomatitis is a very common condition seen frequently by
      dentists in practice. Although the majority of cases are benign and resolve in
      less than two weeks, these ulcerations may be indicative of underlying systemic
      diseases ranging from vitamin deficiency to autoimmunity. Awareness of these
      correlations can help the dentist make or aid the diagnosis of potentially
      serious conditions. There are treatments of which the practitioner should be
      aware that may ameliorate the pain of the ulcerations or shorten their duration.
      The diagnosis and management of this important condition is reviewed in this
      article.

PMID- 12004711
TI  - Oral piercing in athletes: implications for general dentists.
AB  - General dentists need to be aware of the growing number of athletes who display
      various forms of body art. Intraoral piercing and tongue jewelry place athletes
      at greater risk for serious medical and dental consequences that are confounded
      when the athlete attempts to compete while wearing a mouthguard with the tongue
      jewelry in place. All body jewelry should be removed during sporting events.
      General dentists have a professional responsibility to: become more aware of the
      extent and implications associated with tongue piercing in athletes to discourage
      athletes from having the tongue pierced; be prepared to manage postpiercing
      intraoral and dental complications; provide proper advice for the care and use of
      a mouthguard in the presence of tongue jewelry; and develop educational
      strategies that address the medical and dental complications of intraoral
      piercing.

PMID- 12004712
TI  - Use of natural teeth in an interim partial denture.
AB  - A clinical case is presented in which the patient's natural teeth were used in an
      interim partial denture. The patient accepted this treatment despite his
      reluctance to have the periodontally hopeless anterior teeth extracted. This
      technique may be used when the patient is emotionally unprepared for tooth loss,
      when the teeth to be replaced are highly characterized, or when no suitable
      denture tooth is available.

PMID- 12004713
TI  - Multidisciplinary diagnosis and management of orofacial pain.
AB  - Dentistry has enjoyed a remarkable period of technological and scientific growth
      over the past several decades. With the increase in life expectancy, the number
      of individuals seeking dental care also has escalated. One of the most common
      reasons for seeking care is because of pain and/or dysfunction, usually involving
      the teeth or periodontal tissues. However, musculoskeletal, vascular, and
      neuropathic causes of orofacial pain occur frequently. The need to understand
      pain and all of its ramifications is of utmost importance in diagnosis and case
      specific, evidence-based management of conditions afflicting the masticatory
      system. This article reviews current concepts with regard to the multiple
      etiologic and/or perpetuating factors now thought to be associated with myogenous
      and arthrogenous orofacial pain. Important distinctions between acute and chronic
      pain are discussed. The rationale for consideration of multidisciplinary
      evaluation and management is highlighted.

PMID- 12004714
TI  - Waterline biofilm and the dental treatment facility: a review.
AB  - Biofilms are well-organized communities of cooperating microorganisms that can
      include bacteria, protozoa, diatoms, and fungi. Surveys of dental unit waterlines
      (DUWLs) indicate that biofilm formation is a universal problem and that
      environmental and human-derived opportunistic pathogens can be cultured
      consistently from biofilms retrieved from DUWLs and other dental devices.
      Although the health risks presented by waterline bacterial colonization have yet
      to be adequately addressed, professional and ethical considerations indicate that
      steps should be taken to improve the quality of DUWLs. To address these concerns,
      the Council on Scientific Affairs of the ADA recently published a list of
      products cleared by the FDA to control dental waterline contamination. The goal
      of this article is to increase the awareness of potential health risks posed by
      biofilm formation and provide information on techniques and devices designed to
      control the microbial contamination of DUWLs.

PMID- 12004715
TI  - Mandibular radiopacity. Cementoblastoma.

PMID- 12004716
TI  - Mandibular radiolucency. Ameloblastic fibro-odontoma.

PMID- 12004717
TI  - The past and future of dentistry.

PMID- 12004718
TI  - Whatever happened to Hippocrates?

PMID- 12004719
TI  - Technology for dental education: new models, new paradigms, and new
      opportunities.

PMID- 12004721
TI  - We have met The Ethicists and they are us.

PMID- 12004720
TI  - Antibiotics in treating oral-facial infections of odontogenic origin: an update.

PMID- 12004722
TI  - Important factors for accurate impressions.
AB  - A great preparation is only as good as the impression and die made of it.
      Attention to every detail is necessary for a successful clinical result. By
      observing the clinical results, each individual dentist's experience will show
      the observant operator which technique works best. By combining experience,
      attention to detail, and patience, it is possible to achieve great fitting,
      adjustment-free esthetic dentistry.

PMID- 12004723
TI  - Upper lip swelling. Benign salivary gland tumor.

PMID- 12004724
TI  - White mucosa. Chemical burn.

PMID- 12004725
TI  - Cleaning and shaping the apical third of a root canal system.
AB  - The apical third of a root canal system is the most difficult section to clean
      and shape because of its ramifications and tortuosities. This article discusses
      the clinical anatomy of the root and lists the "10 commandments" of cleaning and
      shaping to achieve predictably successful endodontics.

PMID- 12004726
TI  - Endodontic irrigation.
AB  - This review of current research and literature investigates trends in endodontic
      irrigation, focusing on the goals of irrigation and the ability of different
      irrigants to meet these goals.

PMID- 12004727
TI  - Treatment protocol for the management of a sodium hypochlorite accident during
      endodontic therapy.
AB  - During routine endodontic therapy, sodium hypochlorite inadvertently was forced
      out the apex of tooth No. 12. The patient experienced immediate severe pain,
      swelling, and hemorrhage from the canal access. Treatment was palliative,
      including patient education and reassurance, narcotic analgesics, cold and hot
      compresses, and multiple follow-up visits.

PMID- 12004728
TI  - Management of median diastema.
AB  - In mixed and early permanent dentitions, median diastema can be a major esthetic
      concern for patients and/or their parents. The space can be transient or created
      by developmental, pathological, or iatrogenic factors. Different treatment
      techniques have been proposed to manage the situation. This paper reviews the
      common causes of median diastema and presents four cases to illustrate a range of
      restorative and orthodontic options.

PMID- 12004729
TI  - Traumatic bone cyst: report of two cases and review of the literature.
AB  - Traumatic bone cysts usually are found in young individuals and most frequently
      have the radiographic appearance of well-circumscribed radiolucent lesions with a
      tendency to scallop between the roots of the teeth. Two well-documented cases of
      traumatic bone cysts are presented in which some differences related to their
      radiographic features were observed. The possible explanations for these
      differences are discussed and a brief review of the literature regarding the main
      characteristics of traumatic bone cyst lesions also is provided.

PMID- 12004730
TI  - Soft tissue root coverage as treatment for cervical abrasion and caries.
AB  - Root exposure caused by gingival recession may result in cervical abrasion, root
      caries, root sensitivity, and compromised esthetics. Although cervical root
      lesions can be treated with Class V restorations, there may be advantages in
      treating them with soft tissue grafts for root coverage since they restore the
      dento-gingival unit to its prerecession condition. The rationale for root
      coverage with soft tissue grafts is reviewed and two cases are presented of
      successful root coverage procedures in which gingival recession associated with
      cervical abrasion and caries was present.

PMID- 12004731
TI  - Implant reconstruction of a surgical defect.
AB  - This article describes grafting of the surgical defect created from the treatment
      of a mandibular ameloblastoma. Current prosthetic techniques are used and
      demonstrated during the implant-supported reconstruction of the deformity.

PMID- 12004732
TI  - Ridge augmentation with dense hydroxylapatite/resorbable suture matrix.
AB  - The atrophic edentulous ridge represents one of the greatest challenges faced in
      general practice. An estimated 20 million adults in the U.S. are edentulous in at
      least one arch and a significant number of these patients experience problems
      with their prostheses from alveolar bone loss. Many of these patients, for
      various reasons, are not candidates for endosseous dental implants. Alveolar
      ridge augmentation is a viable option in many of these cases; however, this
      procedure has been unpredictable because of particle migration. Presented here is
      a method of ridge augmentation with dense hydroxylapatite beads linked in a
      resorbable suture matrix to prevent particle migration during healing. This
      technique may be performed with minimally invasive surgery, providing long-term
      prosthetic support.

PMID- 12004733
TI  - Rewarding high performers--the pay-for-performance system at Heritage Dental
      Center.
AB  - As it has in many businesses in the U.S., a system rewarding exceptional
      performance has proven to be successful in the dental industry. The effective
      staff incentive program in place at Heritage Dental Center provides benefits for
      all members of the dental team.

PMID- 12004734
TI  - Focus on drug usage to enhance contract performance.

PMID- 12004735
TI  - Programs take the edge off pharmacy cost increases.
AB  - With prescription drug spending going up more than 17% last year and showing no
      signs of easing, health plans and at-risk providers continue to search for ways
      to staunch the bleeding. Here are two proven programs that take the edge off
      pharmacy cost increases.

PMID- 12004736
TI  - Blockbuster drugs coming off patent: will cap contracts benefit?
AB  - Health care organizations and PBMs continue to struggle to find ways to contain
      prescription drug expenditures, but upcoming patent expirations on blockbuster
      drugs may help the bottom line.

PMID- 12004737
TI  - Can e-prescribing reduce drug costs under capitation?
AB  - E-prescribing may offer capitated provider groups new options for improving
      quality of care and patient safety while reducing costs to delivery systems.

PMID- 12004738
TI  - Hospitalists prove their worth for capitated providers, plans.
AB  - For capitated provider organizations, the hospitalist concept is rapidly gaining
      favor as the evidence of cost-effectiveness continues to mount. In the strongest
      evidence published to date, a review of five years of evidence-based hospitalist
      studies reports an average 13.4% cost reduction and 16.6% LOS reduction.

PMID- 12004739
TI  - Manual-based psychotherapies in clinical practice Part 1: assets, liabilities,
      and obstacles to dissemination.

PMID- 12004741
TI  - Evidence-Based Nursing now online at a screen near you:
      www.evidencebasednursing.com.

PMID- 12004740
TI  - Intention to treat analysis in clinical trials when there are missing data.

PMID- 12004742
TI  - Evaluation of studies of treatment or prevention interventions. Part 2: applying
      the results of studies to your patients.

PMID- 12004743
TI  - [The editorial].

PMID- 12004744
TI  - [Study of pesticide poisoning during a nursing course: report of the experience].
AB  - The aim of this paper is to describe the experience of nursing students
      experience in the development of a research project. It began through the
      identification of a public health problem in a farm, when 1,200 people camped
      near a storehouse containing organocloride pesticides. The group decided for a
      descriptive study. The students describe their participation in the project, with
      specialists consultation, bibliographic review, development of a research tool,
      capacitate people to collect data and analysis with statistical help. As a
      conclusion, they point out the limitations encountered, as well as the benefits
      obtained in this experience during undergraduate course.

PMID- 12004746
TI  - [Rural nursing].
AB  - This paper describes the experience of a teacher and four students of the Federal
      University of Rio Grande do Sul within a sitting of members of a rural social
      movement that claims for land in Brazil. The work began with an activity of
      familiarization and ended up being an extension project. The aim of this project
      was the development of a Nursing assistencial model for the population of the
      rural area, considering the specificities of this movement, wishing to adapt
      Nursing teaching to this reality. The author sought for theoretical references in
      Breilh (1999) and Freire (1981). The activities were developed in 1996 and
      consisted of home care and group education.

PMID- 12004748
TI  - [Nursing care of propedeutic and therapeutic nature and its interface with other
      professional actions].
AB  - This paper is based on a qualitative research, with an approach based on
      phenomenological hermeneutics. Its aim is to understand the singularities of
      nursing therapeutic and propedeutic care actions and their interfaces with the
      actions of other professionals. The participants are five nurses from the Trauma
      Intensive Care Unit of an university hospital. The data has been collected
      through semi-structured interviews and has been analyzed according to Ricoeur's
      hermeneutics. The understanding of what has been shown by the participants,
      concerning the meaning of care actions, presented five distinct categories:
      organization of the caring environment; expressiveness of being; development of
      educative actions; systematization of care and interfaces of care.

PMID- 12004749
TI  - Educational mobility: important for the future of the nursing workforce. Kentucky
      Nursing Education Mobility Task Force Secretary.

PMID- 12004750
TI  - Hospice design reflects holistic care.

PMID- 12004751
TI  - Examining BMS (building management systems) issues.

PMID- 12004752
TI  - Spirituality and treatment of people living with HIV disease.

PMID- 12004753
TI  - Herbal therapies and treatment for people living with HIV disease.

PMID- 12004754
TI  - Supreme Court hears arguments in Echazabal 'direct threat' case.

PMID- 12004755
TI  - Global Fund reviews grant applications.

PMID- 12004756
TI  - Health report calls for improved services to minority men.

PMID- 12004758
TI  - Despite national decline, syphilis increases in some cities.

PMID- 12004757
TI  - Physicians say generic AIDS drugs don't threaten R&D.

PMID- 12004759
TI  - Report: Calif. needle-exchange law beneficial, but imperfect.

PMID- 12004760
TI  - Agency says HIV should not bar access to infertility treatments.

PMID- 12004761
TI  - Sen. Helms clarifies AIDS remarks about being 'ashamed'.

PMID- 12004763
TI  - Washington court upholds medical marijuana conviction.

PMID- 12004762
TI  - Johns Hopkins vice dean expected to be named head of NIH.

PMID- 12004764
TI  - Disposal of inmate's blood didn't violate rights.

PMID- 12004765
TI  - HIV-positive individual disabled, District Court affirms.

PMID- 12004766
TI  - New HRSA administrator an enigma to HIV/AIDS activists.

PMID- 12004767
TI  - AIDS vaccines: flickers of progress, but a long way to go.

PMID- 12004768
TI  - Women and the AIDS epidemic: an update.

PMID- 12004769
TI  - Early psychomotor slowing predicts the development of HIV dementia and autopsy
      verified HIV encephalitis.
AB  - OBJECTIVES- To ask if slowed motor speed predicts later human immunodeficiency
      virus (HIV) dementia and HIV encephalitis. METHODS- In 100 deceased acquired
      immunodeficiency syndrome (AIDS) patients prior results from repeated testing of
      the movement reaction time test were correlated with later clinical signs of HIV
      dementia and with neuropathological signs of HIV encephalitis. Autopsy was
      performed in 72 patients. RESULTS- Movement reaction time 1-2 years prior to
      death, or at the time of clinical AIDS diagnosis predicted both development of
      HIV dementia (P<0.05) and HIV encephalitis at autopsy (P<0.01). CONCLUSION-
      Testing for early psychomotor slowing may be used to identify patients at risk of
      HIV dementia and HIV encephalitis.

PMID- 12004770
TI  - WHO lists 40 AIDS drugs.

PMID- 12004771
TI  - Bush plans foreign aids increase.

PMID- 12004772
TI  - Institute of Medicine says minorities get lower-quality care.

PMID- 12004773
TI  - Politics. Republicans plan legislation to increase AIDS funding.

PMID- 12004774
TI  - Microbicides could be on market before HIV vaccines.

PMID- 12004775
TI  - Lawsuits. Court rejects fear of AIDS claim from 'condom' in coke bottle.

PMID- 12004777
TI  - Crime. HIV-positive defendant declared competent to stand trial.

PMID- 12004776
TI  - Maryland schools delay condom education.

PMID- 12004778
TI  - Clinton appointees hold sway over HIV/AIDS advisory council.

PMID- 12004779
TI  - FDA application withdrawn to market Viramune for new use.

PMID- 12004780
TI  - Bush names surprise Surgeon General nominee, NIH head.

PMID- 12004781
TI  - Politics. Bush administration given varied grades by HIV/AIDS coalition.

PMID- 12004782
TI  - San Francisco asks FDA to place STD warning on Viagra.

PMID- 12004783
TI  - [Allergies].
AB  - Prevention is crucial in order to counteract the rising trend of allergies.
      General recommendations, as promoted also in Germany, include the avoidance of
      tobacco smoke. High risk children may benefit from exclusive breast feeding
      (alternatively hydrolyzed formulas), delayed introduction of solid food and a
      reduction of exposure to house dust mite. The meaning of pets is discussed
      controversially at the moment and new promising candidates for prevention emerge
      (e.g., probiotics). There is a need for a systematic development of evidence
      based recommendations.

PMID- 12004784
TI  - [New methods for liver lobe transplantation. Augmentation of liver transplants].

PMID- 12004786
TI  - Schools of medicine. Top schools--primary care.

PMID- 12004785
TI  - [The lactate-ischemia test: expedient diagnosis of myopathy].

PMID- 12004787
TI  - Equilibrium partitioning of chlorinated solvents in the vadose zone: low f(oc)
      geomedia.
AB  - A series of gas (vapor)-advecting water-unsaturated column experiments using a
      low organic content (f(oc)) silica sand was conducted to determine mass
      distributions of chlorinated-volatile hydrophobic organic compounds (C-VHOCs) in
      a natural sorbent system. C-VHOCs used were trichloroethene (TCE),
      tetrachloroethene (PCE), chlorobenzene (CB), and 1,3-dichlorobenzene (DCB). Four
      volumetric water contents (theta(w) = 0.07, 0.12, 0.17, 0.20) and several
      influent gas-phase C-VHOC (solute) concentrations were considered. The method of
      temporal first moments was applied to complete breakthrough curve data to
      determine total C-VHOC gas-phase retardation and associated gas-phase C-VHOC mass
      fraction. Results were compared to an equilibrium partitioning advective
      dispersive formulation of total gas-phase retardation. Literature-derived values
      of Henry's law constants and independent measurements of gas/water interface
      areal extent and interface phase adsorption allowed quantification of C-VHOC mass
      fractions in the aqueous and gas/water interface phases. Unaccounted C-VHOC mass,
      derived from comparison of measured C-VHOC retardation to independent phase
      prediction, was attributed to solid-phase sorption. Results indicate that for all
      conditions tested, gas/water interfacial adsorption exhibited only a small effect
      on C-VHOC vapor retardation (accounting for < or = 10% of the total C-VHOC
      distributions). Solid-phase association was the dominant uptake mechanism,
      accounting for 46-91% of the total C-VHOC mass in the porous system. Evaluation
      of the solid-phase C-VHOC uptake results in terms of a modified form of the
      Dubinin-Radushkevich (DR) isotherm equation provided strong evidence supporting
      the mechanism of pore-filling in this natural, low f(oc) sorbent.

PMID- 12004788
TI  - Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus
      nephritis after diagnosis.
AB  - The purpose of this study was to determine the cumulative incidence of lupus
      nephritis (LN) and the factors predictive of its occurrence in a multiethnic
      systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined
      by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African
      Americans and 91 Caucasians). First, we determined the cumulative incidence of LN
      in all patients. Next, we determined the predictors for LN in those with
      nephritis occurring after diagnosis. The dependent variable, LN, was defined by:
      (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V
      histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria
      attributable to SLE; and/or (3) one of the following features also attributable
      to SLE and present on two or more visits, which were performed at least 6 months
      apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine
      clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or
      > or = 3 granular or cellular casts per hpf. Independent variables assessed at
      diagnosis, and if absent, at baseline, were from four domains: sociodemographic,
      clinical, immunologic and immunogenetic (including the complete antibody profile
      and MHC class II alleles), and health habits. Variables with P < 0.05 by chi
      square analyses were entered into domain-specific stepwise logistic regression
      analyses controlling for disease duration, with LN as the dependent variable.
      Significant domain-specific regression variables (P < or = 0.1) were then entered
      into an overall model. The cumulative incidence of LN was 54.3% in all patients,
      and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in
      43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians,
      P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/
      2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71,
      95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American
      ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living
      together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR =
      1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57,
      P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were
      shown to be significant predictors of the occurrence of LN. Repeated analyses
      excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201
      was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13
      5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics
      and African-Americans with SLE. Sociodemographic, clinical and
      immunologic/immunogenetic factors seem to be predictive of LN occurring after the
      diagnosis of SLE has been made.

PMID- 12004789
TI  - Photo quiz. Sunken cheeks.

PMID- 12004790
TI  - Apoptosis and oncosis in the early progression of left ventricular dysfunction in
      the cardiomyopathic hamster.
AB  - The genetic defect in the cardiomyopathic (CM) hamster is a mutation in the
      glycoprotein-sarcoglycan (a component of the dystrophin-glycoprotein complex).
      Apoptosis has been identified in skeletal muscle of dystrophin-deficient mice,
      and therefore the role of myocardial apoptosis in relation to oncosis in causing
      myocardial necrosis was assessed at the onset of left ventricular (LV)
      dysfunction in CM hamsters. LV size and function were evaluated in normal and CM
      hamsters (CHF147 line) by echocardiography at 1, 2, 3, and 5 months (mo) of age.
      The decrease of LV fractional shortening was found to be most marked (45%)
      between 1 and 2 mo of age. Apop totic nuclei were identified at each time point
      using in situ end-labeling of DNA strand breaks (TUNEL), together with
      immunolabeling of myocytes; DNA fragmentation (laddering) and nuclear morphology
      were also assessed. Myocyte oncotic necrosis was assessed at 2 mo by Evans blue
      dye (EBD), wheat germ agglutinin, hematoxylin/eosin staining, and electron
      microscopy. Apoptotic nuclei were not detected in age-matched normal hamsters. In
      the CM hamsters apoptotic myocyte nuclei comprised an average of 0.041% of
      myocyte nuclei between 1 and 5 mo, an increase at 2 mo (to 0.076%) was not
      significant, and DNA laddering was not detected. The number of myocyte nuclei per
      unit area decreased by 32% between 1 and 2 mo, and in 2 mo old CM hamsters
      myocardial staining with EBD was positive in 9.82% of the myocardial cross
      sectional areas examined, most of which was consistent with sarcolemmal rupture
      and oncosis with inflammatory cell infiltration. It is concluded that myocyte
      oncosis provides the major mechanism for the decreased number of myocyte nuclei
      and the early decrease of cardiac function between 1 and 2 mo of age in the CM
      hamster, with only a small contribution of myocyte apoptosis.

PMID- 12004791
TI  - Harvey Lecture. Oral and pharyngeal cancer education: a long and troublesome
      journey.

PMID- 12004792
TI  - Three classes of pyramidal neurons in layer V of rat perirhinal cortex.
AB  - Whole-cell recordings from 140 pyramidal neurons in layer V of rat perirhinal
      cortex (PR) revealed three distinct firing patterns: regular spiking (RS, 76%),
      burst spiking (BS, 9%), and late spiking (LS, 14%). LS neurons have not
      previously been reported in layer V of any cortical region. LS cells in layer V
      of PR exhibited delays of up to 12 s from onset of a depolarizing current step to
      spike threshold, followed by sustained firing. In contrast, pyramidal cells in
      layer V of other cortical regions contain only RS and BS cells. Within PR, the
      percentage of LS neurons in layer V differs markedly from what we previously
      observed in layers II/III (50% LS) and VI (90% LS). Morphologically, BS neurons
      in layer V of PR had thick primary apical dendrites that terminated in a tuft
      within layer I, whereas RS and LS cells had relatively thin primary apicals that
      terminated either diffusely or in a layer I tuft. At holding potentials near
      rest, PR neurons exhibited small (approximately 15 pA), inward, spontaneous
      postsynaptic currents (PSCs) that were indistinguishable among the three cell
      types. Currents evoked by minimal stimulation of layer I were about 2.8 times
      larger than the spontaneous PSCs. Evoked currents had unusually long onset
      latencies with little variation in latency, consistent with monosynaptic
      responses evoked by stimulation of unmyelinated fibers. The prevalence of LS
      cells in combination with the long-latency monosynaptically evoked PSCs suggested
      that PR is not a region of rapid throughput. This is consistent with anatomical
      data suggesting that PR is a higher-level association cortex. These data further
      advance an emerging picture of PR as a cortical region with a unique distribution
      of cell types different from other cortical regions.

PMID- 12004793
TI  - Applying the resource-based relative value scale to the Emory angioplasty versus
      surgery trial.
AB  - The resource-based relative value scale developed for use in the Medicare fee
      schedule can also be very useful in profiling and comparing physicians'
      cardiovascular utilization across different medical activities. This article
      applies relative value units (RVUs) to data from the Emory Angioplasty versus
      Surgery Trial. The Emory Angioplasty versus Surgery Trial was a randomized
      clinical trial to determine the efficacy of percutaneous transluminal coronary
      angioplasty (PTCA) versus coronary artery bypass surgery (CABG). All physician
      services in the clinical trial provided to 2 groups of patients--those undergoing
      CABG and those receiving PTCA-over the course of 4 years were assigned physician
      work RVUs (representing the intensity of physician work required) and total RVUs
      (representing both the intensity and practice costs). Physician charges were also
      compiled. These data were used to profile and compare physician services to the 2
      groups of patients by type of service, distribution over time, and clinical
      department. Comparisons based on RVUs contrast sharply with differences based on
      charges. Mean physician charges, in 1996 dollars, were $27,158 for CABG patients
      and $21,491 for PTCA patients, a 26% difference (p <0.001). Physician work RVUs
      generated an 18.3% difference (p = <0.001). Using total RVUs, the difference
      between the 2 groups was 3.3% (p = 0.249). Resource-based relative value weights
      are a valuable tool for analyzing and comparing physicians' use of cardiovascular
      resource. The results suggest that conclusions about physician resource
      utilization based on physician charges should be carefully evaluated. When
      possible, physician work RVUs should be compiled and evaluated along with
      physician charges.

PMID- 12004794
TI  - A decrease in cell size accompanies a loss of docosahexaenoate in the rat
      hippocampus.
AB  - Rats raised on n-3 essential fatty acid deficient diets demonstrate spatial
      memory deficits. To investigate neuroanatomical correlates of these deficits,
      morphological analysis of the hippocampus were carried out. Adult, female rats
      were raised for three generations on n-3 deficient or n-3 supplemented diets. Two
      n-3 deficient diets contained adequate linoleic acid (LA), or high linoleic acid
      (high LA), and two supplemented diets contained LA supplemented with alpha
      linolenic acid (+LNA), or linoleic supplementation with alpha-linolenic and
      docosahexaenoic acids (+LNA/DHA). The total fatty acid composition of the
      hippocampus revealed a profound loss (90%) in docosahexaenoic acid (DHA) in the
      hippocampi of LA and high LA animals compared to those on +LNA and +LNA/DHA diets
      with a reciprocal increase in docosapentaenoic acid (DPAn-6) in all phospholipid
      species. The volume, density, total number, and cell body size of neurons in CA1
      3, granular and hilar layers of the hippocampus were measured at septal and
      temporal locations using unbiased stereology. No differences were detected in any
      of these measures except for in cell body size; CA1 pyramidal neurons in the LA
      group were significantly (p < 0.04) smaller than neurons in the +LNA/DHA group at
      the septal location.

PMID- 12004795
TI  - HAART version 2.0.

PMID- 12004796
TI  - Let nevirapine do what it does best.

PMID- 12004797
TI  - Canarypox in the coal mine.

PMID- 12004798
TI  - New targets bring new challenges.

PMID- 12004799
TI  - A T-20 diary.

PMID- 12004800
TI  - The impact of reproductive events on the course of bipolar disorder in women.
AB  - BACKGROUND: Little is known about the impact of female reproductive hormones on
      the course of bipolar disorder. This study was designed to assess the influence
      of reproductive events and hormonal therapies on the course of bipolar disorder
      in women. METHOD: Fifty women with DSM-IV bipolar disorder completed a structured
      clinical interview to assess the impact of reproductive events on the course of
      their illness. RESULTS: The onset of bipolar disorder occurred before menarche in
      32% (N = 16) of women; 18% (N = 9) experienced the onset within 1 year of
      menarche. Most women did not receive an accurate diagnosis of nor treatment for
      bipolar disorder until after they had children, and therefore the majority were
      not treated with mood stabilizers during or immediately after pregnancies. Of
      women with children, 20 (67%) of 30 experienced a postpartum mood episode. Of the
      women who had postpartum episodes after delivery of a first child, all had
      episodes after subsequent pregnancies. Having a postpartum mood episode after a
      first pregnancy significantly increased the risk of a postpartum episode after
      subsequent deliveries (p = .02). Postpartum episodes were almost exclusively
      depressive. Increased depressive symptoms during pregnancy were significantly
      associated with postpartum mood episodes (p = .01). Women who were not using
      hormone replacement therapy (HRT) were significantly more likely than those who
      were using HRT to report worsening of symptoms during perimenopause/menopause (p
      = .02). CONCLUSION: These data suggest that hormonal fluctuations are associated
      with increased risk of affective dysregulation and mood episodes in women with
      bipolar disorder.

PMID- 12004801
TI  - Report of the Texas Consensus Conference Panel on medication treatment of bipolar
      disorder 2000.
AB  - BACKGROUND: The process and outcome of a consensus conference to develop revised
      algorithms for treatment of bipolar disorder to be implemented in the public
      mental health system of Texas are described. These medication algorithms for
      bipolar disorder are an update of those developed for the Texas Medication
      Algorithm Project, a research study that tested the clinical and economic impact
      of treatment guidelines for major psychiatric illnesses treated in the Texas
      public mental health system (Texas Department of Mental Health and Mental
      Retardation [TDMHMR]). METHOD: Academic clinicians and researchers, practicing
      clinicians in the TDMHMR system, administrators, advocates, and consumers
      participated in a consensus conference in August 2000. Participants attended
      presentations reviewing new evidence in the pharmacologic treatment of bipolar
      disorder and discussed the needs of consumers in the TDMHMR system. Principles
      were enumerated, including balancing of evidence for efficacy, tolerability, and
      safety in medication choices. A set of 7 distinct algorithms was drafted. In the
      following months, a subcommittee condensed this product into 2 primary
      algorithms. RESULTS: The panel agreed to 2 primary algorithms: treatment of
      mania/hypomania, including 3 pathways for treatment of euphoric symptoms, mixed
      or dysphoric symptoms, and psychotic symptoms; and treatment of depressive
      symptoms. General principles to guide algorithm implementation were discussed and
      drafted. CONCLUSION: The revised algorithms are currently being disseminated and
      implemented within the Texas public mental health system. The goals of the Texas
      initiative include increasing the consistency of appropriate treatment of bipolar
      disorder, encouraging systematic and optimal use of available pharmacotherapies,
      and improving the outcomes of patients with bipolar disorder.

PMID- 12004802
TI  - Intensity-modulated radiotherapy.
AB  - Intensity-modulated radiotherapy represents a recent advancement in conformal
      radiotherapy. It employs specialized computer-driven technology to generate dose
      distributions that conform to tumor targets with extremely high precision.
      Treatment planning is based on inverse planning algorithms and iterative computer
      driven optimization to generate treatment fields with varying intensities across
      the beam section. Combinations of intensity-modulated fields produce custom
      tailored conformal dose distributions around the tumor, with steep dose gradients
      at the transition to adjacent normal tissues. Thus far, data have demonstrated
      improved precision of tumor targeting in carcinomas of the prostate, head and
      neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal
      tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated
      radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose
      escalation to previously unattainable levels. This experience indicates that
      intensity-modulated radiotherapy represents a significant advancement in the
      ability to deliver the high radiation doses that appear to be required to improve
      the local cure of several types of tumors. The integration of new methods of
      biologically based imaging into treatment planning is being explored to identify
      tumor foci with phenotypic expressions of radiation resistance, which would
      likely require high-dose treatments. Intensity-modulated radiotherapy provides an
      approach for differential dose painting to selectively increase the dose to
      specific tumor-bearing regions. The implementation of biologic evaluation of
      tumor sensitivity, in addition to methods that improve target delineation and
      dose delivery, represents a new dimension in intensity-modulated radiotherapy
      research.

PMID- 12004803
TI  - Isolation perfusion of the liver.
AB  - Thousands of patients die annually from unresectable metastatic or primary
      hepatic cancers confined to liver. Isolated hepatic perfusion (IHP) is a regional
      treatment strategy in which the vascular supply to the liver is isolated and
      perfused with a therapeutic regimen using an extracorporeal circuit consisting of
      a reservoir, heat exchanger, and oxygenator. Drug doses that would cause severe
      toxicities if delivered systemically can be confined to the liver by isolated
      hepatic perfusion, resulting in the ability to intensify treatment to the cancer
      burdened region of the body. Agents and mechanisms commonly used in IHP include
      melphaIan, hyperthermia, and tumor necrosis factor. IHP appears to be efficacious
      for patients with advanced disease, as reflected by large tumor size, high number
      of lesions, or significant overall tumor burden in the liver. In addition,
      responses are observed for patients whose cancer is refractory to systemic and
      hepatic arterial infusion chemotherapy. Recent clinical trials have demonstrated
      that IHP has anti-tumor efficacy against primary hepatic neoplasms and metastases
      from various primary tumors, such as colorectal carcinoma, ocular melanoma, and
      neuroendocrine tumors. Current studies demonstrate that combining hepatic
      arterial infusion with floxuridine after IHP for patients with colorectal cancer
      metastases is associated with significant and durable response rates. Continued
      clinical evaluation is warranted for the use of IHP in the treatment of
      unresectable liver metastases.

PMID- 12004804
TI  - Human chromatid ultrastructure: new observations with scanning and transmission
      electron microscopy.
AB  - Two new observations have been made on human chromatid/chromosome ultrastructure
      using both scanning and transmission electron microscopy (SEM, TEM). A bipartite,
      apparently half-chromatid-like structure was observed in whole human chromosomes
      studied with SEM and in longitudinally sectioned chromosomes analyzed with TEM.
      In addition, we also observed a zipper-like configuration as the parallel sister
      chromatids separated likely due to the supercoiled structure of the chromosome
      and chromatid. It is possible that either or both of these new observations
      resulted from our (improved) method of preparing the chromosomes for SEM and TEM.

PMID- 12004805
TI  - Microlaparoscopic conscious pain mapping in the evaluation of chronic pelvic
      pain: a case report.
AB  - Chronic pelvic pain is a debilitating, life-altering syndrome that negatively
      affects a woman's quality of life and personal relationships. Many women continue
      to suffer with pelvic pain despite having undergone multiple medical and surgical
      treatments. Unfortunately, some women are incorrectly labeled as having
      psychological illness when organic disease may be present. I report a case of a
      woman who underwent multiple pelvic and abdominal surgeries before the cause of
      her pain was identified through microlaparoscopic conscious pain mapping.

PMID- 12004806
TI  - Tumor prevention by 9-cis-retinoic acid in the N-nitroso-N-methylurea model of
      mammary carcinogenesis is potentiated by the pineal hormone melatonin.
AB  - Our laboratory has demonstrated that treatment of MCF-7 breast cancer cells with
      melatonin (Mlt) followed 24h later with physiological concentrations of all-trans
      retinoic acid (atRA) results in apoptosis. These studies were extended into
      trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model.
      Initial studies conducted by feeding the animals 9-cis-retinoic acid (9cRA in the
      chow) and administering melatonin by subcutaneous injection in the late afternoon
      demonstrated that the combination of Mlt and 9cRA was able to significantly
      prevent tumor development, and that the combination was more efficacious that
      either Mlt or 9cRA alone. In this report, we conducted studies to determine if
      lower doses of 9cRA could be used in combination with Mlt while still maintaining
      anti-tumor activity and if the route of administration of 9cRA (bolus (gavage)
      v.s. chronic (chow) routes) affected its interaction with Mlt. The studies
      presented here demonstrate that significantly reduced doses of 9cRA can be used
      in combination with Mlt while maintaining anti-tumor efficacy. Furthermore, our
      studies demonstrate that 9cRA is equally effective when it is administered
      chronically (chow) or as a bolus (gavage). These data demonstrate that the
      combined use of Mlt and 9cRA produces additive or synergistic effects, which are
      more efficacious than 9cRA alone. This combination of Mlt and 9cRA could be a
      potentially useful clinical treatment regimen for breast cancer since it allows
      the use of lower doses of retinoic acid, thus, avoiding the toxic side effects
      associated with the use of high dose retinoids.

PMID- 12004807
TI  - Functional mutations of estrogen receptor protein: assay for detection.
AB  - Antiestrogens block the function of estrogen receptor (ER) by binding and
      misfolding the AF-2 transcriptional activation region in the ligand-binding
      domain, inhibiting or altering its association with coactivator proteins. We
      describe a novel assay uniquely configured to identify aberrations in this
      function that may lead to antiestrogen resistance. The identification of
      mutations of ER that affect its function is important to current breast cancer
      therapies. Standard methods to detect these mutations are cumbersome and the
      number of described mutations is limited, reflecting this difficulty.
      Conventional ER analysis in the clinic demonstrates the presence of antigenic
      determinants of the receptor protein or estrogenic ligand binding without
      reflection on the critical ability of the liganded receptor to interact with
      transcription cofactors. Here, we describe the use of estrogenic regulation of a
      site-specific recombinase activity, measuring deletion of a color marker gene via
      FLP-ER fusion proteins, to detect functional changes in ER protein folding that
      affects the site where cofactors interact. The assay provides a method to readily
      detect single amino acid changes in ER, some with biologically important
      consequences. Without such a functional assay as described, phenotypic changes
      are likely to remain undetected and under-evaluated. It is probable that some
      human tumors have antihormone resistance resulting from ER mutations that either
      block antihormone binding or transmit antihormone binding as a positive
      transcriptional signal via cofactor interaction. An assay to evaluate functional
      ER will lead to better predictive tests of treatment modalities.

PMID- 12004808
TI  - Effect of the addition of ketamine to morphine in patient-controlled analgesia.
AB  - This randomised, double-blind, prospective study compared morphine (1 mg x m(-1))
      with the combination of morphine (1 mg x m(-1)) and ketamine (0.75 mg x m(-1))
      via a patient-controlled analgesia system (PCAS) for postoperative pain control.
      A total of 42 female patients, ASA grade I and II, undergoing elective total
      abdominal hysterectomy was studied. During a standardised anaesthetic, a loading
      dose from the PCA syringe of 10 ml x m(-2) of body surface area was given. A PCAS
      with a background infusion was commenced postoperatively. Pain and side-effects
      were assessed using numerical scoring systems and cardiovascular and respiratory
      parameters were recorded. There was no statistically significant difference
      between the groups in total morphine consumption or pain scoring. Side-effect
      profiles and time to mobilisation were similar. This study concludes that the
      addition of ketamine to morphine, in this dosage regimen, administered via PCAS
      for postoperative pain control, does not confer benefit following total abdominal
      hysterectomy.

PMID- 12004809
TI  - Quality of handover to the postanaesthesia care unit nurse.
AB  - I surveyed 276 patients admitted to the postanaesthetic care unit (PACU). The
      quality of handover to the PACU nurse was assessed by scoring four indicators:
      the quality of verbal information about the patient, the condition of the patient
      on admission, the professional behaviour of the anaesthetist and the nurse's
      satisfaction with the handover. Maximum scores were attained by 32.6% of
      anaesthetists for the quality of condition of the patient. Professional behaviour
      was judged satisfactory or good in 87% of anaesthetists and almost half of the
      anaesthetists (48%) scored full marks for the nurse's satisfaction with the
      handover. The scores of all four indicators were aggregated to give an overall
      impression of quality of handover; this was good in fewer than half the number of
      patients brought to the PACU.

PMID- 12004810
TI  - Obstetric anaesthetists' workload.
AB  - The current recommendation of one consultant session per 500 deliveries with full
      sessional cover for units over 3000 deliveries is arbitrary and is not based on
      workload. The Audit Commission has questioned the wide variability of anaesthetic
      staffing on labour wards. The aim of this study was to investigate whether there
      is a relationship between current workload and obstetric anaesthetic staffing in
      five maternity units. In 1998, a 2-week diary of workload in the participating
      obstetric units was assessed in terms of staffing and clinical and nonclinical
      activities. The busiest time was 08:00 to 12:30. The working patterns between
      consultants and trainees varied considerably. Time spent on nonclinical activity
      by consultants averaged 51%. Any calculation of consultant sessions will need to
      take into account nonclinical activities. Other factors requiring consideration
      are the number of high-risk cases, as well as the number and experience of
      trainees.

PMID- 12004811
TI  - Protective effects of acidosis?

PMID- 12004812
TI  - Activated protein C in the treatment of sepsis.

PMID- 12004813
TI  - Hallucinations related to artificial ventilation in the prone position.

PMID- 12004814
TI  - Breathing system obstruction from intravenous giving set caps.

PMID- 12004815
TI  - Blood contamination of the laryngeal mask airways and laryngoscopes--what do we
      tell our patients?

PMID- 12004816
TI  - The effect of nitrous oxide on the cuff pressure of the laryngeal tube.

PMID- 12004817
TI  - Take off of the pilot tube of the laryngeal mask.

PMID- 12004818
TI  - Glycopyrronium and hypotension following combined spinal-epidural anaesthesia.

PMID- 12004819
TI  - Epidural fixation.

PMID- 12004820
TI  - The influence of abdominoplasty surgery on assessment of level of subarachnoid
      block.

PMID- 12004821
TI  - Target-controlled infusions of propofol and remifentanil with closed-loop
      anaesthesia for hepatic resection.

PMID- 12004822
TI  - Chronic pain funding.

PMID- 12004823
TI  - Patient controlled analgesia (PCA), nurse controlled analgesia (NCA), or epidural
      controlled analgesia (ECA).

PMID- 12004824
TI  - Analysis of Internet usage by anaesthesia trainees in the UK and the USA.

PMID- 12004825
TI  - Not so rare Internet sites.

PMID- 12004826
TI  - Propofol infusion for ICU sedation in children.

PMID- 12004827
TI  - Petrographic and spectroscopic characterization of phosphate-stabilized mine
      tailings from Leadville, Colorado.
AB  - The use of soluble PO4(3-) and lime as a heavy metal chemical stabilization agent
      was evaluated for mine tailings from Leadville, Colorado. The tailings are from
      piles associated with the Wolftone and Maid of Erin mines; ore material that was
      originally mined around 1900, reprocessed in the 1940s, and now requires
      stabilization. The dominant minerals in the tailings are galena (PbS), cerrusite
      (PbCO3), pyromorphite (Pb5(PO4)3Cl), plumbojarosite (Pb0.5Fe3(SO4)2(OH)6), and
      chalcophanites ((Pb,Fe,Zn,Mn)Mn2O5 x 2H2O). The tailings were treated with
      soluble PO4(3-) and lime to convert soluble heavy metals (principally Pb, Zn, Cu,
      Cd) into insoluble metal phosphate precipitates. The treatment process caused
      bulk mineralogical transformations as well as the formation of a reaction rind
      around the particles dominated by Ca and P. Within the mineral grains, Fe-Pb
      phosphosulfates, Fe-Pb sulfates (plumbojarosite), and galena convert to Fe-Ca-Pb
      hydroxides. The Mn-Pb hydroxides and Mn-(+/-Fe)-Pb hydroxides (chalcophanites)
      undergo chemical alteration throughout the grains during treatment. Bulk and
      surface spectroscopies showed that the insoluble reaction products in the rind
      are tertiary metal phosphate (e.g. (Cu,Ca2)(PO4)2) and apatite (e.g. Pb5(PO4)3Cl)
      family minerals. pH-dependent leaching (pH 4,6,8) showed that the treatment was
      able to reduce equilibrium concentrations by factors of 3 to 150 for many metals;
      particularly Pb2+, Zn2+, Cd2+, and Cu2+. Geochemical thermodynamic equilibrium
      modeling showed that apatite family and tertiary metal phosphate phases act as
      controlling solids for the equilibrium concentrations of Ca2+, PO4(3-) Pb2+,
      Zn2+, Cd2+, and Cu2+ in the leachates during pH-dependent leaching. Both end
      members and ideal solid solutions were seen to be controlling solids.

PMID- 12004828
TI  - Hypertension in an adolescent boy.
AB  - We report the case of an adolescent boy who presented with hypertension and
      hypokalemia. A systematic work-up revealed hyperreninemic hyperaldosteronism.
      Further study revealed Page kidney caused by trauma-associated renal hematoma.
      The evaluation and management of hyperaldosteronism and Page kidney are
      discussed.

PMID- 12004829
TI  - HCV/HIV co-infection therapy.

PMID- 12004830
TI  - Radical red.

PMID- 12004831
TI  - Sex, drugs and HIV.

PMID- 12004832
TI  - Structured treatment interruption and immune reconstitution.

PMID- 12004833
TI  - Do boys with attention-deficit/hyperactivity disorder have positive illusory self
      concepts?
AB  - One hundred ninety-five boys with attention-deficit/hyperactivity disorder (ADHD)
      were compared with 73 comparison boys (M = 9.83 years, SD = 1.30) on self
      perceptions relative to a teacher-rated criterion. Emphasis was placed on ADHD
      subgroup comparisons according to level of aggression, academic achievement, and
      depression compared with control boys. Consistent with the authors' prediction,
      ADHD boys overestimated relative to teacher report, more than did controls, in
      the scholastic competence, social acceptance, and behavioral conduct domains.
      Examination of discrepancy scores (child rating - teacher rating) by comorbidity
      subgroups suggested that aggressive and low-achieving ADHD boys tended to
      overestimate their competence the most in the domains in which they were the most
      impaired. Results are discussed in terms of prior literature on "positive
      illusions" in ADHD children.

PMID- 12004834
TI  - Revised anti-kidney stone recipe.

PMID- 12004835
TI  - A better medication for treating breast cancer?

PMID- 12004836
TI  - New solutions for easing chronic nerve pain.

PMID- 12004837
TI  - Vaccines: how, why, and when?

PMID- 12004838
TI  - House calls. Why do you recommend avoiding grapefruit juice when taking certain
      drugs?

PMID- 12004839
TI  - House calls. Why is my doctor recommending that I be treated for polycythemia
      vera even though I feel fine?

PMID- 12004840
TI  - Corrections for range restriction in structured interview ethnic group
      differences: the values may be larger than researchers thought.
AB  - Previous studies of standardized ethnic group differences in the employment
      interview have shown differences to be relatively small. Unfortunately, many
      researchers conducting interview studies have not considered the issue of range
      restriction in research design. This omission is likely to lead to underestimates
      of standardized ethnic group differences (d) when the interview is considered as
      an initial screening device or used in combination with other initial screening
      devices. The authors found that 2 forms of a behavioral interview were associated
      with standardized ethnic group differences of .36 and .56 when corrected for
      range restriction. These differences are substantially larger than previously
      thought and demonstrate the importance of considering a variety of study design
      characteristics in obtaining the appropriate parameter estimates.

PMID- 12004841
TI  - Non-asbestos related diffuse malignant mesothelioma.
AB  - AIMS: The association between asbestos exposure and the development of malignant
      mesothelioma is well known. Nonetheless, a proportion of patients suffering from
      this disease do not appear to have documented exposure to asbestos fibers from
      any known source. Available information suggests that a true "background"
      incidence of this disease exits raising the possibility that other factors
      contribute to its etiology. This paper will review existing data related to non
      asbestos related mesothelioma and suggest avenues for further research. METHODS
      AND STUDY DESIGN: A comprehensive electronic MEDLARS search of the literature
      pertinent to non-asbestos related malignant mesothelioma was performed including
      the years 1996-2001. Hand searches were also carried out to supplement
      electronically derived information and literature pre-dating 1996. The resulting
      references were stratified into the following categories and reviewed; (1)
      radiation associated mesothelioma, (2) familial mesothelioma, (3) dietary
      factors, (4) childhood mesothelioma and (5) the role or SV40. RESULT: Available
      information suggests that genetic factors may play a larger role in the etiology
      of this disease than currently appreciated. The interplay of genes and
      environment require further elucidation in the pathogenesis of mesothelioma. The
      role of diet is poorly understood with few studies directly addressing this
      issue. Whether other environmental or infectious agents are involved in
      mesothelioma development remains speculative. CONCLUSION: The biology of
      mesothelioma is an enigma. Although this disease appears to occur in the absence
      of asbestos exposure, the genetic and biological differences between asbestos
      related and non-asbestos related tumors is unclear. Additional epidemiological
      and laboratory studies are needed to provide a better understanding of the
      relationship between environmental and non-environmental causes of mesothelioma.

PMID- 12004842
TI  - Smoking in Italian women and men, 2001.
AB  - AIMS AND BACKGROUND: To analyze and update smoking prevalence and trends in Italy
      to 2001. METHODS AND STUDY DESIGN: Population-based household survey conducted by
      the DOXA (The Italian Branch of the Gallup International Association) in 2001 on
      a total of 3,296 individuals aged 15 or over, representative of the whole Italian
      population. RESULTS: Overall, 28.9% of the Italian population (34.8% of males,
      23.6% of females) were current cigarette smokers, and a further 0.2% (0.4% of
      males) were cigar or pipe smokers; 14.6% (19.9% of males, 8.7% of females) smoked
      15 or more cigarettes per day. Ex-smokers were 16.6% (25.5% of males, 8.4% of
      females). In males the smoking prevalence steadily declined, from 65.0% in 1957
      to 34.8% in 2001, but the fall was comparatively limited during the last decade.
      In females, the smoking prevalence was below 10% in the 1950s and 1960s, peaked
      at 25.9% in 1990, and declined to 23.6% in 2001. The mean number of cigarettes
      smoked per day, however, tended to increase, reaching 16.4 in 2001 (18.8 for
      males, 12.2 for females). Moreover, compared with legal sales data these figures
      appear underestimated by 25% to 35%. The difference in smoking prevalence between
      males and females tended to increase with age. Among males the smoking prevalence
      was lower in the North, while it was similar among females in various areas of
      the country. CONCLUSION: For the first time since the 1950s the overall smoking
      prevalence in Italian adults fell below 30%, but the figure is now higher than in
      most Western countries. Also for females the smoking prevalence in Italy is now
      higher than in the USA. This reflects the absence of any comprehensive policy and
      legislation against smoking in Italy.

PMID- 12004843
TI  - What gender differences in cancer incidence changed during the last 10 years in
      central Italy?
AB  - AIMS AND BACKGROUND: We have investigated whether gender differences in cancer
      incidence have changed during the mid 1980s to late 1990s, and whether certain
      changes could be clues for gender-specific modifications in carcinogenic
      exposures. METHODS: We used the incidence data from the Tuscany Cancer Registry
      and computed the standardized (on the European standard population) male-to
      female incidence rate ratios (IRR) for two periods, 1986-87 and 1996-97, with
      corresponding 95% confidence intervals. Such statistics were calculated for two
      age groups, 0-59 years and 60 years and over. RESULTS: Among younger subjects
      there was a remarkable reduction in the IRR for smoking-related cancer sites such
      as oral cavity (IRR from 4.3 to 2.2), esophagus (IRR from 6.2 to 4.2), larynx
      (IRR from 13.3 to 5.7), and lung (IRR from 6.5 to 3.3). Less evident changes were
      observed among subjects aged 60 and over, eg for lung the IRR fell from 8.1 to
      6.2. CONCLUSIONS: Most of the differences examined were probably due to changes
      in tobacco smoking which were different between genders during the last decade,
      with a decreasing prevalence of smokers among males and an increasing trend among
      females.

PMID- 12004844
TI  - Amsterdam criteria II and endometrial cancer index cases for an accurate
      selection of HNPCC families.
AB  - Endometrial carcinoma (EC) is the second most common tumor in hereditary
      nonpolyposis colorectal cancer (HNPCC), with an incidence rate of 60% by the age
      of 70 in mutation carriers. The International Collaborative Group on HNPCC
      revised the Amsterdam criteria and proposed a new, wider definition including
      extracolonic cancers. The aim of our study was to evaluate the accuracy of a new
      definition called Amsterdam criteria II. We updated, reclassified and compared
      the pedigrees of 29 women, already reported as being affected by EC and having a
      colorectal cancer familial background, according to the two clinical diagnostic
      criteria for HNPCC (Amsterdam criteria I, ACI, and Amsterdam criteria II, ACII)
      after two periods of observation (1990-1995 and 1995-2000). According to ACII the
      frequency of HNPCC in the population under study increased from 0.9% to 3.7% in
      the period 1990-1995 and from 3.2% to 3.7% in the period 1995-2000. ACII allowed
      early detection of HNPCC families and thus made it possible to provide them with
      a suitable surveillance program and genetic testing.

PMID- 12004845
TI  - Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and
      a comparison with previous meta-analyses.
AB  - AIMS AND BACKGROUND: Up to now adjuvant chemotherapy after curative resection for
      gastric cancer (GC) has been considered an experimental approach. The results of
      existing phase III randomized trials comparing chemotherapy with control after
      surgery are controversial. Three meta-analyses have been published in recent
      years. It is likely that each of them presents a theoretical bias, mainly as
      regards the inclusion criteria of the trials. In this article we re-examine this
      potential bias, highlighting the differences between the present and past meta
      analyses on adjuvant chemotherapy for GC. METHODS: Only randomized controlled
      clinical trials comparing systemic adjuvant chemotherapy with control after
      radical resection of GC were eligible. Total mortality was assessed as outcome
      measure of the treatment effect and a pooled odds ratio was calculated using the
      Peto-Mantel-Haenszel method. RESULTS: After the selection process 17 papers (18
      comparisons) proved eligible for inclusion in the meta-analysis with a total of
      3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the
      control arms; 762 and 871 deaths occurred in the treatment and control arms,
      respectively. Statistical analysis suggests an absence of significant
      heterogeneity between the trials and a significant advantage in survival for
      adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). CONCLUSIONS:
      Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a
      significant survival advantage in patients with GC. However, this observation
      undoubtedly requires confirmation in large randomized controlled trials including
      cisplatin before adjuvant chemotherapy after curative resection for GC can be
      proposed for use in clinical practice.

PMID- 12004846
TI  - Combined radiotherapy and temozolomide in patients with recurrent high grade
      glioma.
AB  - AIMS AND BACKGROUND: There is only little preliminary information about combined
      modality treatment with radiotherapy and temozolamide. The purpose of this
      analysis was to document the feasibility of such combined-modality treatment.
      METHODS: We treated 25 patients with recurrent high grade gliomas after standard
      therapy (surgery and radiation) with the following schedule: 400 mg temozolomide
      orally for five days repeated every 28 days, and radiotherapy at a dose of 20-30
      Gy (2 x 1.2 Gy per day). Four of these patients underwent a second operation
      without complete tumor resection. RESULTS: After 125 courses of temozolomide,
      grade 1 (NCI-CTC) thrombocytopenia was found in four patients and grade 2 in two
      patients. Two patients developed grade 1 leukocytopenia and two others grade 2.
      CTC grade 1-2 nausea was observed in eight patients. For one patient we reduced
      the dose of temozolomide to 300 mg/day because of thrombocytopenia. One patient
      discontinued therapy after the first course because of leukocytopenia and nausea.
      CTC grade 3-4 side effects did not occur. Combined-modality treatment showed no
      more side effects than treatment with temozolomide alone. The median duration of
      response was seven months. CONCLUSION: The observed side effects were tolerable.
      Combined treatment with radiotherapy and temozolomide is feasible. Further
      investigation of this agent is necessary.

PMID- 12004847
TI  - Adjuvant systemic therapy protocol for Dukes' B2 and C resectable colon
      carcinoma.
AB  - AIMS AND BACKGROUND: Trials of adjuvant systemic therapy in high risk patients
      with Dukes' B2 and C colon cancer utilizing 5-fluorouracil-based regimens have
      been ongoing since the 1960s. The aim of this study was to compare the
      combination of 5-FU and leucovorin with the combination of 5-FU and alfa-2b
      interferon (IFN) in patients who had undergone "curative" resection
      foronocarcinoma. STUDY DESIGN: A total of 322 patients with histologically proven
      adenocarcinoma of the colon, Dukes' stage B2 and C, were entered in the study.
      They were randomized to A) leucovorin 20 mg/m2 rapid intravenous injection and 5
      FU 425 mg/m2 IV days 1-5 every 28 days for six cycles or B) 5-FU 600 mg/m2 24
      hour infusion for five days, then 600 mg/m2 IV once a week and IFN 5 MU
      subcutaneously three times a week for six months. RESULTS: There was no
      statistically significant difference in either disease-free survival or overall
      survival. Toxicity was the same in the two groups with the exception of flu-like
      syndrome, which was universal in IFN-treated patients. CONCLUSIONS: There was no
      difference in disease-free survival or overall survival between the two
      combinations in any patient subset. Toxicity was greater with the 5-FU+IFN
      combination because of the flu-like syndrome. These data do not support the use
      of IFN in combination with 5-FU as systemic adjuvant therapy for patients with
      locally advanced colon carcinoma.

PMID- 12004848
TI  - Sentinel lymph node mapping in colorectal cancer: a feasibility study.
AB  - AIMS AND BACKGROUND: Sentinel lymph node (SLN) biopsy is currently used and
      investigated in melanoma and in breast cancer. Its utility in gastrointestinal
      malignancies is still under debate. The prognosis of colorectal cancer patients
      is strongly related to the lymphatic involvement. The aim of this study was to
      evaluate the feasibility of SLN mapping in colorectal cancer and to assess its
      impact on pathological staging and treatment. METHODS AND STUDY DESIGN: We
      injected blue dye in 11 colorectal cancer patients during surgery. After
      resection the tumor specimen was examined to identify blue-stained lymph nodes
      and these lymph nodes were sent separately to the pathologist. Routine
      hematoxylin-eosin examination was performed on all nodes (including blue ones).
      No other techniques (eg immunohistochemistry or PCR) were performed. RESULTS:
      Sentinel lymph nodes were successfully identified in 10 of the 11 patients. We
      observed only one false negative result (10%) and the agreement between SLN and
      other lymph node status was 80% (8/10). One patient was upstaged: SLN was
      positive for metastases while the other lymph nodes were negative. CONCLUSIONS:
      Lymphatic mapping using patent blue dye is feasible in colorectal cancer. The
      identification of lymph nodal metastases by this technique led to upstaging of
      one patient, who may benefit from adjuvant therapy. These initial results prompt
      further investigation of this procedure as an accurate, minimally invasive
      staging approach in early colorectal cancer. We proceed with our study to
      evaluate the role of SLN mapping in colorectal cancer management.

PMID- 12004849
TI  - One hundred and eleven cases of breast conservation treatment with simultaneous
      reconstruction at the European Institute of Oncology (Milan).
AB  - AIMS AND BACKGROUND: Breast conserving treatment (BCT) should provide similar
      quality of local control as mastectomy and avoid psychological distress due to
      mutilation. Randomized trials have demonstrated the value of conservative surgery
      for small tumors. Several publications have indicated the possibility of
      improving the cosmetic result when quadrantectomy is combined with plastic
      surgery. These papers focused on two techniques involving reduction mammaplasty
      and latissimus dorsi flap procedures. At the European Institute of Oncology (EIO)
      we use various plastic procedures to reshape the breast and to improve symmetry.
      The choice of these techniques depends on tumor size and location, as well as on
      breast volume. METHODS AND STUDY DESIGN: In two years (1995 and 1996) 111
      patients were treated at the EIO with quadrantectomy and concomitant plastic
      surgery. Preoperative tumor staging was as follows: T1 57.5%, T2 29%, T3 4.5%,
      Tis 8%, and sarcoma 1%. The tumor locations were upper quadrant 50%, lower
      quadrant 40%, and central quadrant 10%. The plastic surgery techniques used
      included local glandular flaps, areola transposition, mastopexy or classical
      reduction mastoplasty procedures, the round block technique, prosthesis
      insertion, and distal musculocutaneous flaps. Cosmetic evaluation on the basis of
      predefined cosmetic criteria was carried out on photographs after a mean follow
      up of 21 months. In 48 cases the patients' own rating of breast cosmesis was
      asked. RESULTS: The global results were good in 77.5%, fair in 17%, and poor in
      5.5% of the patients. No statistical difference was observed between different
      tumor locations, although the percentage of good cosmetic results, which was
      similar in the upper and lower quadrantectomy groups, was slightly lower for
      centrally located tumors. With regard to the different techniques, we obtained
      100% good results with the round block technique and the Grisotti flap, 87% good
      results with the inferior pedicle, 74% good results with the Lejour and superior
      pedicle techniques, 67% good results with the latissimus dorsi flap, and 58% good
      results with prosthetic implants. The outcome was less satisfactory when no
      contralateral mastoplasty was performed (14 of the 111 cases): 72% good, 14%
      fair, and 14% poor results. These differences were not statistically significant.
      The median weight of the specimens was 157 g, which is almost three-fold the
      usual weight in regular tumorectomies. Six carcinomas were found in contralateral
      breasts (4 DCIS and 2 infiltrating). CONCLUSIONS: The double-team approach
      (plastic surgeons and oncologists) to BCT may improve the final cosmetic result
      following large tumor excisions. It can also extend the indications for breast
      preserving surgery. Moreover, it allows surgical and histological exploration of
      the contralateral breast when a surgical procedure for symmetry is required.

PMID- 12004850
TI  - What is the current role of radiation therapy in the treatment of skin
      carcinomas?
AB  - AIMS AND BACKGROUND: In recent years several radiation therapy units have
      recorded a decline in the number of referrals for the treatment of skin
      carcinomas. This study aims to ascertain whether this decline has also affected
      the radiation therapy unit of Trieste and, if so, to consider the possible
      reasons. METHODS: We retrospectively reviewed all cases of non-melanoma skin
      cancer treated in our unit from January 1986 to December 1999. A database was
      created that would allow rapid and controlled data entry and a sufficiently
      simple query system. RESULTS: The total number of irradiated skin cancers was
      2,219:1,863 basal cell carcinomas, 276 squamous cell carcinomas, and 80
      basosquamous carcinomas. The distribution curves for the number of cases treated
      every year were similar: each of the three types showed a slow and gradual
      reduction in the number of patients referred for radiotherapy. CONCLUSIONS: For
      most authors surgery remains the treatment of choice for skin carcinomas.
      However, radiation therapy can also yield excellent results in terms of local
      control, cosmesis and functionality. In our view the indications for radiation
      therapy are poor general health, elderly age, the presence of diseases that are a
      contraindication for surgery, location of the tumor in the head region, and tumor
      size between 1 and 5 cm.

PMID- 12004851
TI  - Dosimetric evaluation of two radiotherapy treatment planning systems using report
      55 by the AAPM task group 23.
AB  - The AAPM Report 55 of Task Group 23 (TG23) is used to verify the accuracy of the
      calculation algorithm of two radiotherapic treatment planning systems (TPS),
      which use two pencil beam models (one of the last generation) and a collapsed
      cone convolution model. The basic feature of TG23 is that it compares dose values
      computed by TPS and experimental dose measures in situations that reproduce those
      of simple radiotherapeutic treatments. A threshold of 2% was considered for
      discrepancies between computed and measured values. The results gave a good
      accuracy of considered algorithms, except for those points in high dose gradient
      regions, for which the evaluation as a percentage difference, rather than in
      millimeters, may overestimate the discrepancies. It was seen that the TG23
      package is not only an algorithm verification method, but also a useful
      instrument for training with dosimetry, configuration and application of a TPS.

PMID- 12004852
TI  - Clozapine and full-dose concomitant chemoradiation therapy in a schizophrenic
      patient with nasopharyngeal cancer.
AB  - Clozapine is a neuroleptic drug used in selected schizophrenic patients. Its use
      is limited because of unpredictable myelotoxicity. The potentially dangerous
      interaction between cancer treatment and clozapine is virtually unknown. A 37
      year-old schizophrenic patient under treatment with clozapine, diagnosed with
      undifferentiated nasopharyngeal carcinoma, was treated with full-dose cisplatin
      and concomitant radiotherapy without reporting significant neutropenia. Clozapine
      may be cautiously administered when full-dose concomitant chemoradiation therapy
      is required.

PMID- 12004853
TI  - Prostate cancer presenting as a solitary cerebellar metastasis. A case report and
      review of the literature.
AB  - We describe a case of a 70-year-old patient with sudden onset of gait ataxia,
      headache, dizziness and dysarthria. Magnetic resonance imaging revealed a
      solitary lesion in the left cerebellar hemisphere with strong and irregular
      enhancement of the contrast medium, surrounded by extensive edema. Rectal
      examination revealed an abnormally enlarged and stiff left prostate lobe, and
      ultrasound-guided transrectal biopsies showed prostate adenocarcinoma of mild
      differentiation. Neurosurgical intervention and histopathologic examination
      revealed metastatic prostate adenocarcinoma. The patient underwent orchiectomy
      and was given antiandrogens. He is still alive and closely followed. According to
      the literature, prostate cancer presenting as a solitary cerebellar metastasis is
      an extremely rare clinical problem.

PMID- 12004854
TI  - Paraneoplastic Cushing's syndrome associated to locally advanced thymic carcinoid
      tumor.
AB  - BACKGROUND: Thymic carcinoid is a frequent cause of Cushing's syndrome due to
      ectopic adrenocorticotropin secretion. Histology and immunohistochemistry allow
      differential diagnosis from other epithelial thymic tumors, such as thymomas and
      thymic carcinomas. The term used to name this tumor is confusing, since it is a
      malignant neuroendocrine neoplasm, and therapeutic approaches need to bear that
      in mind. CASE REPORT: Unlike most cases of thymic carcinoid associated to
      Cushing's syndrome that had distant metastases at diagnosis, we report a 50-year
      old male who presented with Cushing's syndrome and was diagnosed with thymic
      carcinoid without distant metastases. Multimodal treatment with surgery,
      radiotherapy and chemotherapy (cisplatin plus etoposide) induced a complete
      clinical and biochemical remission lasting for 46 months.

PMID- 12004855
TI  - Small bowel metastases of lung cancer as unique metastatic lesions: CT, MRI and
      small bowel enema findings. a case report.
AB  - Small bowel metastases of lung cancer as unique secondary lesions are a very rare
      occurrence and may be clinically missed due to the aspecificity of the symptoms.
      Diagnosis is usually made at acute abdominal symptomatology that requires
      emergency surgical treatment. We report a case of 69-year-old woman, previously
      treated for epidermoid lung carcinoma, complaining only of aspecific asthenia;
      blood cell count and chemistry showed a moderate but progressive anemia; no signs
      of small bowel occlusion were present. The follow-up CT scan showed two large
      masses at the small bowel level, without any evidence of hepatic, lung, adrenal
      or brain metastases. MRI and small bowel enema confirmed the presence of the
      masses, and the diagnosis of small bowel metastases was hypothesized. Surgical
      specimens of the masses confirmed the radiological suspicion.

PMID- 12004856
TI  - Juvenile granulosa cell tumor of the testis: case report and review of
      literature.
AB  - Juvenile granulosa cell tumor of the testis is an infrequent tumor of the gonadal
      stroma characteristic of the pediatric age. It usually appears as a scrotal mass
      and less frequently as an abdominal or inguinal mass. It may be associated with
      ambiguous genitalia and/or abnormal sex chromosomes. The recommended treatment is
      orchiectomy alone because local recurrence or metastasis have never been
      observed. We describe a patient with a juvenile granulosa cell tumor of the
      testis and review the literature.

PMID- 12004857
TI  - Leydig cell tumor: a case report and review of the literature.
AB  - We report a case of Leydig cell tumor, which is a rare testicular neoplasm. Most
      of them are benign. Malignant Leydig cell tumor is associated with a poor
      prognosis. The clinical features and treatment of Leydig cell tumor are discussed
      in this case report.

PMID- 12004858
TI  - 28th meeting of the Italian Cancer Society (SIC). New challenges of molecular
      oncology.

PMID- 12004859
TI  - Development and evaluation of an ICD-10 telepsychiatry training programme in
      Western Australia.

PMID- 12004860
TI  - The Italian national telemedicine programme.
AB  - The Italian national telemedicine programme included a broad range of research
      projects, but they all served the common purpose of bringing about improvements
      in health-care management and performance. The programme consisted of seven
      projects, each of which had specific research and training objectives, and a
      three-year duration. The systems developed in the course of the programme were
      not experimental prototypes:they were intended to be pre-commercial systems. The
      functional and clinical merits of the products and systems developed were
      evaluated, and their costs and benefits measured with reference to those already
      in use. The seven projects were completed in 1999. The Italian Ministry of
      Universities, Research and Technology granted research funds totalling 50,000,000
      Euros for the whole programme. While the results of the research were promising,
      successful projects alone are not sufficient to reduce costs in health-care.
      Indeed, far more money can be saved simply by encouraging the uptake on a larger
      scale of many technologies and practices that already exist.

PMID- 12004861
TI  - A neighbor's perspective on Josef E. Fischer.

PMID- 12004862
TI  - CDC's campaign to prevent antimicrobial resistance in health-care settings.

PMID- 12004864
TI  - 2 vaccines reach 2nd stage of clinical trials.

PMID- 12004863
TI  - Diagnostic value of succinate ubiquinone reductase activity in the identification
      of patients with mitochondrial DNA depletion.
AB  - Mitochondrial DNA (mtDNA) depletion syndrome (McKusick 251880) is characterized
      by a progressive quantitative loss of mtDNA resulting in severe mitochondrial
      dysfunction. A diagnosis of mtDNA depletion can only be confirmed after Southern
      blot analysis of affected tissue. Only a limited number of centres have the
      facilities to offer this service, and this is frequently on an irregular basis.
      There is therefore a need for a test that can refine sample selection as well as
      complementing the molecular analysis. In this study we compared the activities of
      the nuclear-encoded succinate ubiquinone reductase (complex II) to the activities
      of the combined mitochondrial and nuclear-encoded mitochondrial electron
      transport chain (ETC) complexes; NADH:ubiquinone reductase (complex I), ubiquinol
      cytochrome-c reductase (complex III), and cytochrome-c oxidase (complex IV), in
      skeletal muscle biopsies from 7 patients with confirmed mtDNA depletion. In one
      patient there was no evidence of an ETC defect. However, the remaining 6 patients
      exhibited reduced complex I and IV activities. Five of these patients also
      displayed reduced complex II-III (succinate:cytochrome-c reductase) activity.
      Individual measurement of complex II and complex III activities demonstrated
      normal levels of complex II activity compared to complex III, which was reduced
      in the 5 biopsies assayed. These findings suggest a possible diagnostic value for
      the detection of normal levels of complex II activity in conjunction with reduced
      complex I, III and IV activity in the identification of likely candidates for
      mtDNA depletion syndrome

PMID- 12004865
TI  - AIDS activists converge on Capitol to rally for Global Fund increase.

PMID- 12004866
TI  - $1 million CDC partnership to fight AIDS in South Africa.

PMID- 12004867
TI  - Prisoner's constitutional rights not violated over late meds.

PMID- 12004868
TI  - Criminal charges. Woman in landmark AIDS case could return to prison.

PMID- 12004869
TI  - Former employer not required to pay legal fees, court rules.

PMID- 12004870
TI  - Confidentiality. Doctors protected from N.Y. employment-at-will policies.

PMID- 12004871
TI  - Tax law. HIV-positive man not disabled under IRS statute, court finds.

PMID- 12004872
TI  - STDs. Officials say CDC notification delay helped spread of herpes.

PMID- 12004873
TI  - Management team to fill leadership void at CDC.

PMID- 12004874
TI  - HHS awards $923 million in HIV/AIDS grants.

PMID- 12004875
TI  - Thailand markets low-cost, 3-in-1 antiretroviral medication.

PMID- 12004876
TI  - Diagnosis and management of the HCV/HIV-coinfected patient.

PMID- 12004877
TI  - Is high-grade dysplasia on anal Pap a high-grade problem?

PMID- 12004878
TI  - The value of resistance testing.

PMID- 12004879
TI  - Resistance in intermittent TB therapy.

PMID- 12004880
TI  - Are short interruptions safe?

PMID- 12004881
TI  - A test for mitochondrial toxicity.

PMID- 12004883
TI  - [Reflections on the Perruche judgment].
AB  - The Perruche case has been widely talked about. By conceding the responsibility
      of a doctor who did not detect that a pregnant woman had rubella, the plenary
      meeting of France's highest court of appeal acknowledged a causal link between a
      doctor's mistake (diagnostic error) and a child's disability. Not only is this
      outcome open to criticism from a legal point of view, as the doctor is not
      responsible for a disability linked to the mother's rubella, but it is also
      questionable on an ethical basis. The doctor's error did not cause the disability
      of the child but only the birth of this disabled child (if the mother had been
      aware of her state, she probably would have terminated her pregnancy). This
      judicial decision therefore implies that the birth of a disabled child can
      constitute a prejudice. Even if the judges' intention was to compensate the
      disabled child and this was reaffirmed in recent decisions, such judicial
      precedents deserve to be contested.

PMID- 12004884
TI  - Current awareness in pharmacoepidemiology and drug safety.

PMID- 12004885
TI  - Specific characteristics of food passage through the digestive tract in meadow
      voles.

PMID- 12004886
TI  - Species composition of winter bacterioplankton in two Siberian ponds determined
      by the 16s rRNA sequence analysis.

PMID- 12004887
TI  - Intraspecies interactions in the bank vole: field observation data.

PMID- 12004888
TI  - Plasmid DNA modulates chronic graft-versus-host reaction.

PMID- 12004889
TI  - Update on the Complementary and Alternative Medicine (CAM) Task Force. Kentucky
      Nurses Association for the Legislative Task Force on Complementary and
      Alternative Medicine.

PMID- 12004891
TI  - JAMA patient page. Papillomavirus.

PMID- 12004892
TI  - Development and mapping of SSR markers for maize.
AB  - Microsatellite or simple sequence repeat (SSR) markers have wide applicability
      for genetic analysis in crop plant improvement strategies. The objectives of this
      project were to isolate, characterize, and map a comprehensive set of SSR markers
      for maize (Zea mays L.). We developed 1051 novel SSR markers for maize from
      microsatellite-enriched libraries and by identification of microsatellite
      containing sequences in public and private databases. Three mapping populations
      were used to derive map positions for 978 of these markers. The main mapping
      population was the intermated B73 x Mo17 (IBM) population. In mapping this
      intermated recombinant inbred line population, we have contributed to development
      of a new high-resolution map resource for maize. The primer sequences, original
      sequence sources, data on polymorphisms across 11 inbred lines, and map positions
      have been integrated with information on other public SSR markers and released
      through MaizeDB at URL:www.agron.missouri.edu. The maize research community now
      has the most detailed and comprehensive SSR marker set of any plant species.

PMID- 12004894
TI  - Bibliography of journal articles (January to June 2001).

PMID- 12004895
TI  - The R. A. Fisher Collection at Adelaide University.

PMID- 12004893
TI  - Insertion-deletion polymorphisms in 3' regions of maize genes occur frequently
      and can be used as highly informative genetic markers.
AB  - Single-nucleotide polymorphisms (SNPs) are the most frequent variations in the
      genome of any organism. SNP discovery approaches such as resequencing or data
      mining enable the identification of insertion deletion (indel) polymorphisms.
      These indels can be treated as biallelic markers and can be utilized for genetic
      mapping and diagnostics. In this study 655 indels have been identified by
      resequencing 502 maize (Zea mays) loci across 8 maize inbreds (selected for their
      high allelic variation). Of these 502 loci, 433 were polymorphic, with indels
      identified in 215 loci. Of the 655 indels identified, single-nucleotide indels
      accounted for more than half (54.8%) followed by two- and three-nucleotide
      indels. A high frequency of 6-base (3.4%) and 8-base (2.3%) indels were also
      observed. When analysis is restricted to the B73 and Mol7 genotypes, 53% of the
      loci analyzed contained indels, with 42% having an amplicon size difference.
      Three novel miniature inverted-repeat transposable element (MITE)-like sequences
      were identified as insertions near genes. The utility of indels as genetic
      markers was demonstrated by using indel polymorphisms to map 22 loci in a B73 x
      Mo17 recombinant inbred population. This paper clearly demonstrates that the
      resequencing of 3' EST sequence and the discovery and mapping of indel markers
      will position corresponding expressed genes on the genetic map.

PMID- 12004896
TI  - History of medicine's hidden treasures.

PMID- 12004897
TI  - [The scourge of smallpox].

PMID- 12004898
TI  - [The humanity of Pedro Lain Entralgo].

PMID- 12004899
TI  - Poor, ill, and sometimes abandoned: tubercular children in Buenos Aires, 1880
      1920.
AB  - Ill children with chronic diseases, such as tuberculosis, have faced difficult
      lives. Poverty proved a factor in their susceptibility to disease, their
      abandonment, and their treatment. When public health policies in Buenos Aires
      shifted from ignoring children to viewing them as victims who needed protection,
      government agencies, charitable organizations, public schools, and hospitals
      developed special programs that emphasized both prevention and cure of childhood
      tuberculosis. Argentine physicians and hygienists supported programs that were
      similar to those in Europe and the United States. Despite efforts, from 1880 to
      1920, diagnosis of tuberculosis remained problematic, health professionals failed
      to prevent tuberculosis in children, and physicians were unable to cure the
      disease.

PMID- 12004900
TI  - A company of women and men: men's recollections of childbirth in medieval
      England.
AB  - The events that took place in medieval English birthing chambers were witnessed
      and assisted by a company of women. Although these events may have been isolated,
      they did not exist in isolation. Rather, they interacted in complex ways with the
      lives and activities of the men in the manor hall. This article examines those
      interactions as they are evidenced in proof-of-age inquests, legal documents that
      record the recollections of husbands, fathers, and male relatives and neighbors
      regarding the events surrounding the birth of an heir to crown land. It concludes
      that even though men rarely entered the birthing chamber, their dynastic
      interests and social politics routinely penetrated its walls, blurring the
      boundary between private and public spheres, female and male space.

PMID- 12004901
TI  - Retraction.

PMID- 12004902
TI  - Looking at child labor.

PMID- 12004903
TI  - Coral reef biodiversity and conservation.

PMID- 12004904
TI  - Coral reef biodiversity and conservation.

PMID- 12004905
TI  - Teaching pharmacy history: the Antipodean experience.

PMID- 12004906
TI  - Apothecary to Mr Harriot.

PMID- 12004907
TI  - Apothecaries and hospital assistants in Colonial India.

PMID- 12004908
TI  - Pharmacy in Malta under the French (12 June to 1 September 1798).

PMID- 12004909
TI  - The changing role of the community pharmacist in health promotion in Great
      Britain 1930 to 1995.

PMID- 12004910
TI  - Teaching pharmacy history: the antipodean experience.
AB  - This paper, co-authored by Dr. Rosemary Beresford, the Associate Dean of
      Undergraduate Programmes in the School of Pharmacy at the University of Otago, in
      New Zealand was presented by Mr Geoffrey Miller to the 75th Anniversary Congress
      of the International Society for the History of Pharmacy, held in Lucern
      Switzerland in September 2001.

PMID- 12004911
TI  - Tasmania: green pastures for the Browne family of pharmacists.
AB  - This is the story of another Pharmacy dynasty, the Brownes of Tasmania, who can
      trace three generations of pharmacists from the one family, going back to 1882.

PMID- 12004912
TI  - Quacks: fakers and charlatans in medicine.
AB  - Quackery abounded in Britain in the 16th to the 19th centuries. Some of these
      practitioners were colourful characters who successfully promoted their medical
      and surgical abilities and their remedies to a gullible public. Although many may
      have been harmless, a number of them may have been considered to be rather
      dubious and dangerous, but altogether they played a large part in influencing the
      history of medical practice between 1750 and 1850. The methods of practice
      employed by these people have been reviewed and examples given of such quacks as
      Sir William Read and Joshua Ward both of whom were very successful. Alternative
      medicine has always had an attraction for some members of the community, and this
      has extended into the twentieth century. Examples are given of therapies, such as
      that for the treatment of cancer and arterial disease, in recent years that can
      only be described as modern-day quackery.

PMID- 12004913
TI  - [Keeping an eye on Brazil: medical geography and Alphonse Rendu's journey].
AB  - This article emphasizes the important role Natural History has played in the
      production of medical knowledge from the end of the eighteenth century on. It
      also tries to clarify the strategic position Brazilian empire came to have in the
      nineteenth century in relation with etiologically and environmentally oriented
      research programs under the patronage of Medical Geography. The analysis of the
      French physician Alphonse Rendu's travel reports, from 1844 to 1845, leads to the
      recognition of a very specific period of that branch of European medical schools.
      Besides, the article provides the recognition of a second period of Medical
      Geography, that starts with the creation of th Archives de Medecine Navale in the
      1860's.

PMID- 12004914
TI  - [The divine bottle: voyages, alcohols, and remedies in the two hemispheres, 16th 
      20th centuries].

PMID- 12004915
TI  - Control of haemodynamic response to tracheal intubation in cigarette smokers
      compared with non-smokers.
AB  - Some authors have demonstrated that a bolus dose of 1 microg/kg followed by an
      infusion rate of 0.5 microg/kg/min is adequate to attenuate the haemodynamic
      response to laringoscopy and tracheal intubation. In this study we have evaluated
      the efficacy of Remifentanil in controlling haemodynamic and some neuroendocrine
      responses to tracheal intubation in smokers compared with non-smokers. We studied
      126 patients, ASA I-II, aged 20-49 yr, submitted laparoscopic cholecystectomy (66
      male, 60 female); sixty-three patients were non-smokers and 63 patients smoked 10
      or more cigarettes per day. Anaesthesia was induced with thiopental 3-5 mg/kg and
      remifentanil 1 microg/kg. Vecuronium 0.1 mg/kg was administrated to facilitate
      tracheal intubation. Immediately after intubation heart rate of smokers (mean
      101.2 +/- 17 beat/min) was significantly higher (p < 0.001) than non-smokers
      (mean 90.2 +/- 14 beat/min) and also the neuroendocrine responses of smokers
      (epinephrine value 155 +/- 173 pcg/ml; norepinephrine value 276 +/- 164 pcg/ml)
      was significantly higher (p < 0.01) than non-smokers (epinephrine 95 +/- 75,
      norepinephrine 154 +/- 76). These findings may be clinically important to
      evaluate the risk of ischaemic heart diseases.

PMID- 12004916
TI  - Insulin formulations--a review.
AB  - Although the improvement on insulin therapy since it was first conceived, it is
      still far from mimicking physiological secretion of pancreatic b-cells and
      research to find new insulin formulations and new routes of administration
      continues. Human biosynthetic insulin (rapid-acting, intermediate-acting and long
      acting), produced by recombinant DNA technique, is currently available. The
      pharmacokinetic profile of rapid-acting insulin (regular) does not adequately
      reproduce the physiological post-prandial insulin response. This has led to the
      development of molecular analogues with slight modifications that prevent the
      spontaneous polymerisation underlying delayed absorption. Fast-acting analogues
      such as Lyspro and Aspart can be injected immediately before the meal, inducing a
      very fast and substantial peak of insulin, similar to that produced by b-cells,
      but have the disadvantage of short duration of action. For this reason, and
      because of the difficulty of obtaining sufficient basal insulin concentrations to
      control preprandial blood glucose levels with current long-acting insulins,
      analogues known as Glargine and Detemir have been synthesized. They have
      virtually no plasma peak and acts for about 24 h. These characteristics make it
      ideal to cover basal insulin requirement. With insulin analogues, it also seems
      possible to overcome the problem of intra- and inter-individual variability in
      absorption after subcutaneous injection. This variability is directly
      proportional to the duration of insulin action. Research into new routes of
      administration has led to production of inhaled insulin powder, soon to become
      commercially available. Insulin is absorbed through the lung alveoli. Trials to
      evaluate efficacy and toleration have shown that inhaled insulin has a similar
      kinetic profile to the fast-acting injected analogue and can therefore be used
      for mealtime requirement, combined with a single daily injection of long-acting
      insulin. Oral insulin is currently being studied in type 1 diabetes prevention
      with promising results.

PMID- 12004917
TI  - Surgical treatment of differentiated microcarcinomas of the thyroid.
AB  - Thyroid microcarcinomas (TMC) are histologically malignant diseases, despite
      their limited dimensions and non-aggressive behaviour; frequent multifocality of
      the disease and local recurrence is really possible after conservative resection.
      Modern therapeutic approaches to thyroid microcarcinoma include both radical
      surgical treatment, influenced by the frequent locoregional diffusion of TMC,
      consisting of a total thyroidectomy with an eventual central and/or functional
      unilateral lymphadenectomy, depending on the clinical evidence of lymh node
      metastases and conservative treatment based on more limited resections which take
      into account the slow clinical progression of this type of tumour. The aim of our
      work is to examine the therapeutic guidelines for surgical treatment of TMC
      which, in our experience, are closely dependent on clinical presentation type.
      From 1991 to 2000, more than 400 patients with thyroid disease were referred to
      the Department of Surgical Science and Applied Medical Technologies "F. Durante".
      Threehundred-seventythree patients received surgical treatment: in 311 patients a
      benign disease was diagnosed, while in 62 neoplasia was present. In total we
      observed 30 TMC, consisting of 28 papillary and 2 follicular microcarcinomas. On
      the basis of clinical presentation we divided patients in three groups: A-
      patients with a clinically suspicious neoplastic lesion before surgical
      treatment; B--patients in whom histological diagnosis of cancer was "incidental"
      after an operation performed for benign disease; C--patients in whom a neck lymph
      node metastases were clinically found before diagnosis of an "occult" papillary
      carcinoma in the thyroid gland. 27 total thyroidectomies and 3 conservative
      resections, that required successive total exeresis, were performed. In 5 cases a
      central neck lymph node dissection was carried out and in 5 + 1 cases functional
      modified lateral neck dissections was deemed necessary. Our data suggest that an
      evaluation of tumor's malignancy cannot be carried out on the basis of its
      dimensions alone. Indeed, biological aggressivity, whether local or at a
      distance, is a prerogative of both large and small tumours. Therefore a
      microcarcinoma must be considered a full-blown form of thyroid cancer and as such
      must be treated. Total thyroidectomy may be followed by identification of
      possible local metastases. "Whole body" scintigraphy allows to identify and treat
      with radioiodine therapy, possible recurrent lesions. Therefore in conclusion,
      total resection is not only a useful, but also a necessary treatment for the
      correct diagnostic and therapeutic follow-up of these patients.

PMID- 12004918
TI  - Direct detection of diarrheagenic Aeromonas from faeces by polymerase chain
      reaction (PCR) targeting aerolysin toxin gene.
AB  - Detection of diarrheagenic Aeromonas specific aerolysin toxin (Aer) gene by PCR
      based assay and isolation, identification of diarrhea causing Aeromonas from
      faeces by culture methods were carried out in the Division of Active
      Surveillance, National Institute of Cholera and Enteric Diseases (NICED),
      Kolkata, India for a period of 12 months. Out of 602 faecal samples collected
      from patients with acute diarrhea admitted in Infectious Diseases (ID) Hospital,
      Kolkata, 68 (11.29%) samples were found to be possessing Aer gene by PCR
      technique. The conventional culture methods using selective media yielded only 64
      (10.6%) Aeromonas strains from the same faecal samples. The different Aeromonas
      species possessing Aer gene identified by PCR based technique include A.
      hydrophila (55.8%), A. caviae (17.6%), A. veronii (10.2%), A. schubertii (4.4%),
      A. jandaei (2.9%) and A. trota (8.8%). The isolation and identification of
      Aeromonas by routine culture did not detect enterotoxigenic A. trota present in
      four diarrheal faecal samples. The failure of the growth of enterotoxigenic A.
      trota on selective media may be attributed to the ampicillin susceptibility of
      those strains. The quality control studies revealed that PCR method for the
      direct detection of Aer gene from the faeces has the sensitivity of 100% and
      specificity of 98%.

PMID- 12004919
TI  - Pathogenesis of atopic dermatitis (AD) and the role of allergic factors.
AB  - OBJECTIVE: In this paper we will demonstrate that the exact pathogenesis of
      atopic dermatitis (AD) remains enigmatic, however the central defect is
      genetically determined, and the several dysfunctions we will highlight all point
      to a vicious cycle of allergen exposure, allergen-specific IgE production, and
      chronic Th2 cell stimulation. An important role is played by the late phase of
      IgE-mediated hypersensitivity, and evidence is accumulating that eosinophils
      actively participate in late phase-allergic reactions also in the skin.
      OBSERVATIONS: AD is the first atopic disease to appear in the absolute sense:
      dendritic cells (DC) develop firstly in the skin and then in lung, in addition to
      homing receptors for T lymphocytes that are selective for skin localizations and
      not for lung. Among the DC, a primary role is reserved to Langerhans cells (LC)
      that express E-cadherin, a homophilic adhesion molecule that is prominently
      represented in epithelia. In addition keratinocytes and the interleukins (IL)
      they express are capable of activating a host of IgE-bearing cells. CONCLUSION:
      Although much new information regarding the pathogenesis of AD has evolved over
      the past several years, the basic underlying etiology of this disorder remains
      elusive. Preventive measures are the only treatment for AD. We hope that the
      coming years will witness the development of new strategies for the treatment of
      AD, aimed at specific targets based on a thorough understanding of its
      pathogenesis.

PMID- 12004920
TI  - An assessment of asbestos body formation in extrapulmonary sites: liver and
      spleen.
AB  - STUDY OBJECTIVES: Asbestos bodies (ABs) form as asbestos fibers become coated by
      a cellular iron- and protein-rich matrix. ABs have been reported in lymph nodes
      and a few extrapulmonary sites, but no data exist as to their formation outside
      of the lung. It is not clear whether the AB found in these extrapulmonary areas
      have been transported as mature structures from the lung or formed at the
      extrapulmonary site. This study was designed to determine if ABs are produced in
      extrapulmonary sites. The guinea pig efficiently forms ferruginous bodies in the
      lung and so it was chosen as a model to test the coating efficiency of amosite
      asbestos fibers in lung, liver and spleen. DESIGN: Sized amosite asbestos (5 mg)
      was administered either endotracheally into lung (n = 2) or directly into liver
      (n = 4) and spleen (n = 4) of healthy 10-week-old male guinea pigs. The lung,
      liver and splenic tissues were removed at 40 and 180 days post inoculation and
      were examined histologically for the presence of AB via light microscopy.
      Uncoated fibers isolated from the tissues were characterized by electron
      microscopy. The coating efficiency was calculated as a ratio of uncoated/coated
      fibers per organ. RESULTS: The coating efficiency ratios of fibers that were
      collected at 40 days post-injection from the individual sites were: lung - 350:1,
      liver - 4200:1, and spleen - 220,000:1. At 6 months post-injection the ratios for
      the individual sites consisted of: lung - 176:1, liver - 11,000:1, and spleen -
      1000:1. CONCLUSION: This study indicates that AB can be formed in extrapulmonary
      sites and that the coating efficiency in the lung is much greater than that
      within the liver or spleen.

PMID- 12004921
TI  - Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro
      percutaneous penetration from coal dust.
AB  - To understand the dermal uptake of chemicals bound to soil and dust, information
      on the neat substance is helpful but does not seem sufficient. Because of its
      content of polycyclic aromatic hydrocarbons (PAHs) coal is suspected to be
      carcinogenic. However, experimental carcinogenity studies on coal dust never
      succeeded in demonstrating a higher incidence of cancer in treated animals. The
      aim of the study was to assess dermal penetration through human skin of PAHs from
      coal dust. A sample of coal dust was grinded and sieved, using the particle size
      of < 30 microm. An in vitro static diffusion cell system validated by in vitrolin
      vivo comparison has been used to study dermal penetration through human skin of
      PAHs from coal dust compared with their percutaneous absorption as pure
      compounds. No percutaneous penetration of PAHs was observed in the cells where
      coal dust was applied, while dermal penetration was demonstrated for PAHs applied
      in an acetone solution. Results agree with the literature that PAHs are poorly
      absorbed through the skin from solids. Dermal risk assessment of PAHs should take
      into account not only the degree and the extent of skin contamination, but also
      their bioavailability, which is heavily influenced by the physico-chemical
      characteristics of the matrix.

PMID- 12004922
TI  - Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel
      aerosol inhalation.
AB  - Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation
      induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced
      inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months;
      adult, 12 months; half in each age group) were randomly assigned to the exposure
      or control groups. Mice were nose-only exposed to room air or atmospheres of 1000
      mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary
      mechanics, respiratory permeability, lavaged cell profile, and chemical mediators
      in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8
      jet fuel had similar values with regards to increased lung dynamic compliance,
      lung permeability, BALF cell count, and decreased PGE2. However, there were
      several different responses between the young-versus-adult mice with respect to
      BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8
      jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory
      mechanisms leading to lung injury and dysfunction in the younger-versus-adult
      mice.

PMID- 12004923
TI  - Effects of butylparaben on the male reproductive system in rats.
AB  - Parabens are a group of compounds widely used as preservatives in foodstuffs,
      cosmetics, toiletries and pharmaceuticals. These compounds are known to exert a
      weak estrogenic activity, with butylparaben showing the most potent activity
      among methyl-, ethyl- and propyl esters in in vitro recombinant yeast assay and
      in in vivo uterotrophic assay. To account for potential reproductive effects in
      male animals, butylparaben was administered to 3-week-old Wistar rats divided in
      groups of eight subjects, at doses of 0.00%, 0.01%, 0.10% and 1.00% with the
      animal's diet. After 8 weeks, the rats were killed by decapitation and the
      weights of the testes, epididymides, prostates, seminal vesicles and preputial
      glands were recorded. The absolute and relative weights of epididymides were
      decreased in a dose-dependent manner and the decrease was statistically
      significant at 0.10% and above. The cauda epididymal sperm reserve of all treated
      groups was significantly decreased. The sperm count of the group receiving the
      highest dose was 58.2% of control values. The daily sperm production (DSP) in the
      testis was also significantly lower in all treated groups when compared to
      controls. Serum testosterone concentration was lowered dose-dependently and was
      significant at 0.1% or more. The daily intake of butylparaben that caused these
      disruptions is similar to the lower level of acceptable daily intake (ADI) for
      parabens in the European Community (EC) and in Japan. The results of the present
      experiments show for the first time that exposure of a postweaning mammal to
      butylparaben had an adverse effect on the secretion of testosterone and in the
      functions of the male reproductive system.

PMID- 12004924
TI  - Age distribution of cancer in mice: the incidence turnover at old age.
AB  - We have studied cancer incidence in mice as a function of age in those cohorts
      where the rodents are allowed to live very close to their full natural lifetime.
      We find that the incidence rises as a function of age, but then flattens and
      turns over at an age of about 800 days. This behaviour is similar to that which
      we observed (Pompei and Wilson, 2001) in the Surveillance, Epidemiology, and End
      Results (SEER) data where the age distribution of human cancer incidence turns
      over at about age 80. Although other fits are possible, the three-parameter beta
      function model fits both the mouse data and the human data well. The beta model
      implies, and the data do not deny, the interpretation that cancer is not a
      certainty and mice may also outlive their cancers, although high-dose cohort
      results suggest cancer might be certain if dose is sufficiently high. Limited
      data suggest that the cancer age distribution, including the turnover, may be
      time shifted by dietary restriction.

PMID- 12004925
TI  - Non-viral mediated gene transfer of porphobilinogen deaminase into mammalian
      cells.
AB  - Acute intermittent porphyria (AIP) is an inborn error of heme synthesis in which
      the third enzyme, porphobilinogen deaminase (PBGD), is deficient. The disease is
      characterized by recurrent attacks of acute abdominal pain often accompanied by
      neuropsychiatric symptoms. Current therapeutic treatment with heme is only
      palliative and no curative alternative exists. The present report describes the
      first step towards a gene therapy treatment for AIP. Mouse cDNA encoding the PBGD
      enzyme was cloned and four vectors containing the full-length mouse and human
      cDNA of the housekeeping and erythroid PBGD isoforms under the control of a
      cytomegalovirus promoter were constructed. The vectors, condensed to
      polyethylenimine, were successfully transfected to NIH 3T3 and HeLa cells as
      determined by enzymatic activity measurements. Thus, the PBGD activity was
      increased 3-10 times in NIH 3T3 cells and 95-240 times in HeLa cells. The
      expression was shown to be dose and time dependent, with the highest level of
      activity observed in HeLa cells after 72 h posttransfection. Non-viral gene
      transfer was also undertaken in PBGD-deficient fibroblasts established from an
      AIP patient. Complete normalization of the PBGD activity was accomplished after
      the addition of 2.5 microg DNA per well. Further addition of DNA increased the
      PBGD activity up to threefold the normal value. The study documents a successful
      gene transfer and a high degree of PBGD expression in different cell-lines,
      indicating a potential for future gene therapy in AIP.

PMID- 12004926
TI  - Different effects of immobilization stress on the mRNA expression of antioxidant
      enzymes in rat peripheral organs.
AB  - To understand the role of antioxidant enzymatic defenses in reactive oxygen
      species (ROS) injury following immobilization stress, we examined the effect on
      mRNA expression of four antioxidant enzymes, manganese superoxide dismutase (Mn
      SOD), copper and zinc containing SOD (Cu/Zn-SOD), glutathione peroxidase (GPx)
      and catalase (CAT), in peripheral rat organs. Immediately after 6h of
      immobilization, the mRNA levels of all antioxidants examined were markedly
      decreased in the liver, while 24 h after the cessation of immobilization, the
      mRNA expressions recovered to baseline levels. In contrast, the adrenal mRNA
      levels of Mn-SOD and CAT were increased by stress, and the increased levels of
      these mRNAs were maintained 24h after cessation of stress. The stress did not
      affect the mRNA levels of antioxidants in the heart, lung and kidney. Our results
      suggest that the antioxidant defense status in peripheral tissues is influenced
      by immobilization stress and that tissue-specific regulation mechanisms of
      antioxidant enzymes exist in rats.

PMID- 12004927
TI  - Source of group II phospholipase A2 in gastric juice.
AB  - Gastric juice contains both pancreatic group I phospholipase A2 (PLA2-I) and
      synovial-type group II phospholipase A2 (PLA2-II), which may play a crucial role
      in Helicobacter pylori infection and gastric mucosal injury. PLA2-I present in
      gastric juice is derived from pancreatic acinar cells. The cellular source of
      PLA2-II found in gastric juice is unknown. A specific cell type of the intestinal
      mucosa, the Paneth cell, is known to secrete PLA2-II. The purpose of the present
      study was to define the source of PLA2-II present in gastric juice. For this
      purpose, gastric juice was collected from 29 individuals during gastroscopy, and
      mucosal biopsies were taken from the antrum and body of the stomach and from the
      duodenum as well as from the jejunum of individuals with resected stomach, for
      immunohistochemical detection of PLA2-II. The concentration of bilirubin in the
      gastric juice samples was determined to identify duodenogastric regurgitation.
      The PLA2-II content was significantly higher in bilirubin-positive than in
      bilirubin-negative gastric juice samples. PLA2-II was localized by
      immunohistochemistry in Paneth cells in three patients with areas of intestinal
      metaplasia of the gastric mucosa and in Paneth cells of duodenal and jejunal
      mucosa in all patients, but not in any other epithelial cell type of the mucosa
      of the stomach or the small intestine. Inflammatory cells did not contain PLA2
      II. The current results suggest that PLA2-II found in gastric juice is derived
      from the Paneth cells of the small intestinal mucosa.

PMID- 12004928
TI  - Plasma cystatin C as a marker of renal function in patients with liver cirrhosis.
AB  - Cystatin C is a low molecular weight protein and the plasma level of cystatin C
      is mainly determined by glomerular filtration, making cystatin C an endogenous
      marker of glomerular filtration rate. The aim of the study was to elucidate the
      applicability of plasma cystatin C as a marker of renal function in patients with
      liver cirrhosis. Serum cystatin C and creatinine concentrations were compared
      with creatinine clearance. Thirty-six patients (14 females and 22 males aged
      between 33 and 81 years) with liver cirrhosis with normal to severely impaired
      kidney function were included. Plasma cystatin C was measured by an automated
      particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma
      creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine
      were found to increase with decreasing values of creatinine clearance. The
      reciprocal values of cystatin C and creatinine were compared with those for
      creatinine clearance revealing an r2 of 0.37 and 0.18, respectively. Comparison
      of the areas under the curves (AUC) of the non-parametric receiver-operating
      characteristic plots for plasma cystatin C (AUC=0.7364; SE=0.0929) and plasma
      creatinine (AUC=0.6309: SF=0.1028) revealed a significant difference between
      plasma cystatin C and plasma levels of creatinine (p-value=0.03). The results
      demonstrate that the diagnostic accuracy of plasma cystatin C was better than
      plasma creatinine in identifying liver cirrhotic patients with reduced glomerular
      filtration rate.

PMID- 12004929
TI  - Measurement of blood and plasma coagulation time using free oscillating
      rheometry.
AB  - An assay based on free oscillating rheometry to measure the activity of
      coagulation factors is described. The method can be used in blood and plasma and
      is particularly suitable for screening and monitoring coagulation disturbances in
      point-of-care testing (POCT) in environments where quick analysis with minimal
      preanalytical work is needed. In this study the endpoint as clotting onset time
      (COT) is determined by a deviation from initial viscoelastic properties of an
      oscillating sample. The model system entails the clotting of citrated blood or
      plasma clotting by repletion of Ca2+. COT was shown to give a dose-dependent
      response to added thrombin and to be resistant to high concentrations of corn
      trypsin inhibitor, indicating measurement of the tissue-factor-dependent pathway
      of coagulation activation. COT in recalcified blood and plasma covariated with
      prothrombin time (PT) according to Owren, and activated partial thromboplastin
      time (aPTT). The technique and instrument used proved to be quick and easy to
      handle, and suitable for POCT as well as for examinations in the laboratory.

PMID- 12004930
TI  - Serum cystatin C for assessment of glomerular filtration rate in pregnant and non
      pregnant women. Indications of altered filtration process in pregnancy.
AB  - Serum cystatin C is believed to reflect the glomerular filtration rate (GFR) more
      closely than serum creatinine in many contexts and a reference interval for serum
      cystatin C in term pregnancy has been defined to enable its use also in pregnant
      women. However, serum cystatin C levels were not found to be decreased in term
      pregnancy, though GFR of low molecular mass substances is known to increase by at
      least 40% by the third trimester. The aim of this study was therefore to
      determine whether serum cystatin C is a reliable GFR marker also in pregnant
      women. GFR was determined by measurement of plasma clearance of iohexol in 48
      previously healthy women in their third trimester and in 12 healthy nonpregnant
      women, and was compared with their serum levels of cystatin C and creatinine.
      Both serum cystatin C and creatinine levels were significantly related to GFR for
      both pregnant and non-pregnant women. However, the correlation between cystatin C
      and GFR was set at different levels for pregnant and nonpregnant women. Our
      results indicate a physiological difference between the filtration processes in
      kidneys of pregnant and non-pregnant women, whether it is size-dependent,
      configuration-dependent or charge-dependent. Nevertheless, serum cystatin C seems
      to reflect GFR reliably in both non-pregnant and pregnant, healthy and
      hypertensive women.

PMID- 12004931
TI  - Effect of a common reference plasma on the inter-laboratory variation of the
      measurement of total and free protein S: a collaborative study of the Dutch
      Working Group on Haemostasis Laboratory Diagnosis.
AB  - The comparability of test results for protein S between laboratories is hampered
      by a high inter-laboratory variability. The effect of the use and type of common
      reference plasma on the inter-laboratory variability of the total and free
      protein S measurement was evaluated. The results of 10 plasma samples measured
      against a centrally distributed frozen plasma and a centrally distributed
      lyophilized plasma were compared with those of various local reference plasmas
      regularly used by the 11 participating laboratories. The mean intra-assay
      coefficient of variation for total protein S in each laboratory varied from 3.8
      to 12.8% (mean intra-assay CV of all laboratories: 7.4+/-2.3%); for free protein
      S this range was 3.1 to 13.3% (mean intra-assay CV of all laboratories: 6.6+/
      2.7%). We confirmed the high inter-laboratory coefficient of variation (mean+/
      SD) with the several local reference plasmas for both total protein S (13.4+/
      5.6%; n = 10) and free protein S (17.1+/-7.5%: n = 11). For total protein S, the
      inter-laboratory CV was reduced to 11.5+/-4.8%, (p=0.05) by using a common frozen
      reference plasma, while it was increased to 16.8+/-3.4%, (p=0.022) using a common
      lyophilized reference plasma. For free protein S, these values decreased only
      statistically significantly for the common lyophilized reference plasma, to
      15.1+/-6.0%, (p = 0.008). For free protein S, the dilution factor used was
      identified as a factor influencing the inter-laboratory variability. This study
      shows that, for both types of protein S measurements, using one frozen reference
      plasma shows a slight decrease in inter-laboratory variability, while a common
      lyophilized plasma shows inconsistent results. It is concluded that further
      investigation is necessary to examine other sources of variability to increase
      the comparability of laboratory results for both total and free protein S.

PMID- 12004932
TI  - Can capillary whole blood glucose and venous plasma glucose measurements be used
      interchangeably in diagnosis of diabetes mellitus?
AB  - According to new proposals from the American Diabetes Association (ADA) and WHO,
      venous peripheral plasma is the preferred system for measuring glucose for
      diagnosing diabetes mellitus. Owing to the instability of glucose in plasma after
      blood sampling, strict well-defined and standardized preanalytical conditions are
      essential to ensure that glucose concentration measured in plasma reflects real
      blood glucose in the patient. This is in contrast to the capillary whole blood
      measurements, which are easy to perform and well established. We investigated
      whether it is possible to perform analysis on capillary whole blood but express
      the results as plasma glucose values and hence obtain comparable results and the
      same predictive values for diagnosis in the individual patient? The conclusion of
      our investigations is that these two systems are not interchangeable and that
      conversion should not be done for diagnostic purposes where plasma determinations
      are recommended.

PMID- 12004933
TI  - Elevated levels of trypsinogen-2 and trypsin-2-alpha1-antitrypsin in sera of
      infants and children after cardiac surgery.
AB  - Acute pancreatitis is a known complication of cardiac surgery with
      cardiopulmonary bypass but amylase is not a reliable marker in infants. We
      evaluated whether the serum concentrations of trypsinogen-2 and trypsin-2-alpha1
      antitrypsin (AAT) can be used to study disturbances in pancreatic function in
      children and infants undergoing cardiac surgery. The study comprised 21 infants <
      1 year and 25 children aged 1-16 years undergoing cardiopulmonary bypass at the
      Children's Hospital, Helsinki University Central Hospital. Consecutive serum
      samples were taken before surgery, at 12 h, 1, 2 and 3 days after surgery, and
      before discharge from the hospital. A moderate increase in trypsinogen-2 and
      trypsin-2-AAT in serum was found in more than two-thirds of the patients. On day
      3, there was a 4.3-fold mean increase (CI 95% 2.8-6.5) in trypsinogen-2 and a 2.4
      fold mean increase (CI 95% 1.8-3.1) in trypsin-2-AAT. In 4 patients trypsinogen-2
      was elevated by more than 20-fold. One patient had clinical pancreatitis, but
      there were no clinical signs of pancreatitis in the other three patients. The
      changes in trypsinogen-2 and trypsin-2-AAT were similar in infants and children.
      The moderate increase in the serum concentrations of trypsinogen-2 and trypsin-2
      AAT after cardiac surgery in the absence of signs of pancreatitis may be due to a
      subclinical pancreatic disturbance, but it could also be caused by an
      inflammatory response and expression of extrapancreatic trypsin. Contrary to
      amylase, trypsinogen-2 is expressed in the pancreas of infants.

PMID- 12004934
TI  - Renal and cardiac function during alpha1-beta-blockade in congestive heart
      failure.
AB  - The kidney and the neurohormonal systems are essential in the pathogenesis of
      congestive heart failure (CHF) and the physiologic response. Routine treatment of
      moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE)
      inhibition and beta-blockade. The need for control of renal function during
      initiation of ACE-inhibition in patients with CHF is well known. The aim of this
      study was to investigate whether supplementation by a combined alpha1-beta
      blockade to diuretics and ACE-inhibition might improve cardiac function without
      reducing renal function. METHODS: Fourteen patients treated for moderate to
      severe CHF with diuretics and ACE inhibitors were investigated at baseline, after
      4 months of maximum carvedilol treatment and after withdrawal of carvedilol.
      RESULTS: Carvedilol lowered blood pressure and heart rate but increased left and
      right ventricular ejection fractions without changing cardiac output or pulmonary
      blood volume. At the same time, a minor fall was seen in glomerular filtration
      rate (GFR). but renal blood flow was unchanged and effective renal plasma flow
      slightly increased. Carvedilol also lowered the plasma levels of angiotensin II
      and aldosterone. All changes were reversed after withdrawal of carvedilol.
      CONCLUSIONS: Carvedilol augments ACE-inhibitor-induced vasodilation by lowering
      blood pressure, and angiotensin II beside reducing heart rate. The heart adapts
      to the haemodynamic alterations without changes in cardiac output and pulmonary
      blood volume. GFR is slightly lowered despite no changes in renal blood flow and
      a slight increase in effective renal plasma flow. The study emphasizes the need
      for control of renal function during treatment with carvedilol in patients with
      CHF.

PMID- 12004935
TI  - Polymer-additive extraction via pressurized fluids and organic solvents of
      variously cross-linked poly(methylmethacrylates).
AB  - Variously cross-linked poly(methylmethacrylates) (PMMAs) are synthesized with
      three additives incorporated at theoretically 1000 microg of the additive per
      gram of prepared polymer. The additives are Irganox 1010, Irganox 1076, and
      Irgafos 168. The in-house" synthesized polyacrylates are then subjected to
      supercritical fluid extraction (SFE) to determine if additive recovery is a
      function of percent cross-linking. Although considerable work in this regard has
      been performed with non-cross-linked polyolefins, the literature is lacking
      regarding polyacrylates. Some additive degradation apparently occurs during the
      synthesis, as judged by the increased complexity of the extract high-performance
      liquid chromatographic trace and the low percent recoveries observed especially
      for the Irganoxes. For low polymer cross-linking (1%), it appears that both PMMA
      synthetic reproducibility and readily observed polymer swelling during SFE are
      serious issues that adversely affect additive percent recovery and precision of
      results. Higher percent cross-linking yields more consistent analytical data than
      low percent cross-linking, even though the amount of additive extracted in all
      PMMA samples (regardless of cross-linking percentage) is essentially the same
      whether the extraction is via SFE or liquid-solid extraction with methylene
      chloride. Results for comparably cross-linked poly(ethylmethacrylate) and
      poly(butylmethacrylate) are similar to PMMA.

PMID- 12004936
TI  - The surface properties of tetradecyltrimethylammonium bromide observed by
      capillary electrophoresis.
AB  - The electroosmotic flow (EOF) is measured as a function of
      tetradecyltrimethylammonium bromide (TTAB) concentration and is shown to have
      distinct zones that are pH dependent. The data is correlated with previously
      proposed surface structures ranging from unimolecular adsorption to hemimicelles
      and micelles of TTAB adsorbed on the hydrated fused silica. A plot of the TTAB
      concentration at zero EOF versus pH shows that the zero point of charge (zpc) is
      pH dependent and that a linear extrapolation of the data intercepts close to the
      pH value for the zpc of a fused-silica surface. This shows that different surface
      properties at different pH values at any given TTAB concentration are generally
      dealt with. Therefore, these pH-dependent structures of the fused-silica surface
      have to be taken into account while studying these phenomena.

PMID- 12004937
TI  - Characterization of paint samples used in drinking water reservoirs:
      identification of endocrine disruptor compounds.
AB  - Several migration tests are performed from various epoxy paint samples that,
      according to the regulation, can be used in food reservoirs such as drinking
      water reservoirs. The level of the organic compounds capable of producing
      migrations to water with special attention to endocrine disruptor compounds
      (EDCs) are identified and estimated by closed loop-stripping analysis (CLSA) and
      liquid-liquid extraction (LLE) methods coupled with gas chromatography (GC)-mass
      spectrometry (MS). Bisphenol A, a strong endocrine disruptor, is found in all
      migration experiments. Its concentration level reaches between 0.02 and 0.03
      mg/cm2. The higher concentration corresponds with benzylic alcohol, which is used
      as a solvent and curing agent in epoxy paint. Other EDCs identified in the
      migration tests are phthalates, 4-nonylphenol, and t-butylphenol. The main non
      EDCs identified are solvents, antioxidants, and rubber-like compounds. No great
      differences are found in the use of metallic plates or concrete slabs for
      migration experiments; only additional compounds related with the pretreatment of
      the concrete wall have been identified, too. In the study of a drinking water
      sample the same organic compounds identified in the migration test is not seen.
      This is probably because of the dynamic situation in a drinking water reservoir.
      Finally, a GC profile of a direct epoxy paint analysis is shown. The main peak
      identified is bisphenol A diglycidyl ether, monomer, and an active principle of
      the polymerization of epoxy resins based on bisphenol A. In addition, we report
      the recoveries of a selected group of EDCs using CLSA and LLE methods coupled
      with GC-MS.

PMID- 12004938
TI  - An HPLC method for the determination and pharmacokinetic study of cinnamic acid
      in the plasma of rats having taken the traditional Chinese medicinal preparation
      Ling-Gui-Zhu-Gan decoction.
AB  - A high-performance liquid chromatographic method for the determination and
      pharmacokinetic study of cinnamic acid in the plasma of rats after having been
      administrated orally with the traditional Chinese medicinal (TCM) preparation
      Ling-Gui-Zhu-Gan decoction is established. Plasma samples taken from rats are
      acidified with hydrochloric acid and extracted with ethyl acetate. Separation of
      the main effective constituent cinnamic acid is accomplished on a C18 stationary
      phase and a mobile phase of methanol-acetonitrile-2% glacial acetic acid
      (10:22:70, v/v) with a UV detector setting at 254 nm. After validation, the
      method is used to take a limited view of pharmacokinetic profiles of the TCM
      preparation of the Ling-Gui-Zhu-Gan decoction.

PMID- 12004939
TI  - Analysis of CL-20 in environmental matrices: water and soil.
AB  - Analytical techniques for the detection of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12
      hexaazatetracyclo(5.5.0.05,9.03,11)dodecane (CL-20) in water and soil are
      developed by adapting methods traditionally used for the analysis of
      nitroaromatics. CL-20 (a new explosives compound) is thermally labile, exhibits
      high polarity, and has low solubility in water. These constraints make the use of
      specialized sample handling, preparation, extraction, and analysis necessary. The
      ability to determine the concentrations of this new explosive compound in
      environmental matrices is helpful in understanding the environmental fate and
      effects of CL-20; understanding the physical, chemical, and biological fate of CL
      20; and can be used in developing remediation technologies and determining their
      efficiency. The toxicity and mobility of new explosives in soil and groundwater
      are also of interest, and analytical techniques for quantitating CL-20 and its
      degradation products in soil and natural waters make these investigations
      possible.

PMID- 12004940
TI  - Determination of aromatic acids and nitrophenols in atmospheric aerosols by
      capillary electrophoresis.
AB  - A capillary zone electrophoresis method is developed for the determination of
      aromatic organic acids and nitrophenols in atmospheric aerosols. The procedure is
      based on sampling atmospheric particulate matter on quartz fiber filters and the
      extraction and analysis of the extracts by capillary electrophoresis. Separation
      conditions are optimized by varying the pH and acetonitrile content of the
      electrolyte buffer. Separations in a 20% acetonitrile-20 mM borate mixture (pH
      9.9) are able to resolve all of the geometric isomers of hydroxybenzoic acid,
      phthalic acid, benzenetricarboxylic acid, and nitrophenol as well as 1,2,4,5
      benzenetricarboxylic acid, m-toluic acid, and sulfosalicylic acid. A buffer
      consisting of 11% acetonitrile-20 mM borate (pH 9.9) is found to be most suitable
      for the analysis of atmospheric aerosol samples. Detection limits are in the
      order of 40 to 130 ng/mL. Intersample migration time reproducibility is generally
      better than 1.5%, with day-to-day variations under 3%. A general extraction
      scheme using diethyl ether-HCl in combination with a preconcentration step is
      developed. Recoveries of spiked standards range from 59% to 102%, with relative
      standard deviations ranging from 2% to 17% for five determinations. The method is
      applied towards the analysis of ambient aerosol samples as well as vehicle
      emission studies with promising results, thus showing it to be a potential
      complement to already existing methodology for the analysis of organic acids and
      nitrophenols in atmospheric aerosols.

PMID- 12004941
TI  - Assay of TNP-470 and its two major metabolites in human plasma by high
      performance liquid chromatography-mass spectrometry.
AB  - In this study, a sensitive, specific assay for the determination of TNP-470 and
      its two major metabolites M-IV (also know as AGM-1883) and M-II in human plasma
      is reported. The assay involves liquid-liquid extraction of acidified plasma
      followed by reversed-phase high-performance liquid chromatography-atmospheric
      pressure chemical ionization-tandem mass spectrometry. A liquid-liquid extraction
      using an organic solvent mixture (methyl-tert-butyl-ether-hexane, 1:1, v/v) is
      used in place of solid-phase extraction because it provides consistent recoveries
      for all analytes, including the internal standard. Retention times for the
      analytes and internal standard are less than 7 min. Within- and between-day
      precision is < or = 6.5% and < or = 13.3% relative standard deviation,
      respectively, for the three analytes. The lower limits of quantitation are 0.25,
      0.5, and 1.0 ng/mL for TNP-470, M-IV, and M-II, respectively.

PMID- 12004942
TI  - Determination of lamotrigine simultaneously with carbamazepine, carbamazepine
      epoxide, phenytoin, phenobarbital, and primidone in human plasma by SPME-GC-TSD.
AB  - A simple and rapid analytical method is presented for the determination of
      lamotrigine simultaneously with primidone, carbamazepine, carbamazepine epoxide,
      phenobarbital, and phenytoin in human plasma using solid-phase microextraction
      (SPME) and gas chromatography with thermionic specific detection. The best
      conditions for the SPME procedure is established as following: direct extraction
      on a 65-microm Carbowax-divinylbenzene fiber; 1.0 mL of a sample plasma matrix
      modified with 15% NaCl and 3 mL of a potassium phosphate buffer (pH 7.0);
      extraction temperature at 30 degrees C; and stirring at a rate of 2500 rpm for 15
      min. The method shows good linearity between 0.05 and 40.0 microg/mL with
      regression coefficients ranging between 0.9965 and 0.9995 and a coefficient of
      variation of the points of the calibration curve lower than 10%. The lowest limit
      of quantitation for the plasma-investigated drugs varies from 0.05 to 0.20
      microg/mL, according to the drug. The proposed method is sensitive enough to work
      into subtherapeutic and therapeutic concentrations, being that it is applied in
      pharmacokinetic studies and patient routine therapeutic drug monitoring.

PMID- 12004943
TI  - Liquid chromatography in the analysis of neurotransmitters and alkaloids.
AB  - Several thin-layer chromatographic (TLC) and high-performance liquid
      chromatographic (HPLC) systems for the determination of biogenic amine
      neurotransmitters, alkaloids, and the metabolites of these two groups of
      compounds are developed. The possibility of the interference of these compounds
      is investigated. In all the systems developed for neurotransmitters, the
      retention of alkaloids is examined and vice versa. In TLC because of different
      visualization procedures (a dyeing reagent for alkaloids and visible light for
      neurotransmitters), compounds of both the groups may be determined simultaneously
      without the risk of interference. In HPLC, similarly, the possibility of false
      diagnosis through simultaneously employing the fluorimetric and diode-array
      detectors can be excluded.

PMID- 12004944
TI  - Retention times are dependent on the person setting up the GC and installing the
      column. What is causing this?

PMID- 12004945
TI  - How to adjust eluents to optimize HPLC separations.

PMID- 12004946
TI  - Subjective health complaints.
AB  - A variety of subjective illnesses with few or no objective findings have appeared
      at regular intervals as epidemics in our society under different labels. There
      are few or no objective findings that might explain the "disease" or the
      complaints go beyond what is regarded as "reasonable" by the physician. Muscle
      pain and other types of subjective health complaints are among the most frequent
      reason for encounters with general practitioners, and one of the major causes for
      sickness absence. The prevalence of subjective health complaints is very high,
      with at least 75% of the population reporting one or more subjective health
      complaints the past 30 days. From a statistical point of view, it is "normal" to
      have complaints. It is when they become intolerable that assistance is required.
      The difficult thing is that this threshold is individual and subjective. The
      psychiatric definitions of these complaints, therefore, refer only to the tip of
      an iceberg.

PMID- 12004947
TI  - Sensitization, conditioning, and learning: can they help us understand
      somatization and disability?
AB  - This paper reviews those features of non-associative and associative forms of
      learning, as elaborated in the experimental literature, that might contribute to
      experienced and reported discomfort in the workplace. Emphasis is given to
      sensitization, while noting that some models of habituation (e.g. the opponent
      process model) also produce sensitization-like effects as a by-product that could
      contribute to persistent complaints. Also noted are ways in which these non
      associative processes may enhance associative learning of workplace-avoidance
      behaviors that are exceptionally persistent - even in the absence of further
      somatic discomfort.

PMID- 12004948
TI  - Cognitive-emotional sensitization and somatic health complaints.
AB  - Sensitization is conceptually related to cognitive bias in experimental
      psychopathology, and they share the basic mechanism of neuronal sensitization.
      Every strongly relevant individual concern, like fears, can yield cognitive bias
      or "cognitive-emotional sensitization". It might also be present for bodily and
      environmental information related to illness, and could be an etiological factor
      in medically unexplained complaints. Physiological and cognitive sensitization
      are theoretically compared. There is evidence for cognitive-emotional
      sensitization in some medically unexplained somatic complaints, and negative
      affect is suggested as a catalyst. Prolonged cognitive-emotional sensitization
      ("perseverative negative cognition" or worry, rumination) might even have
      demonstrable somatic pathological effects. It is concluded that sensitization may
      be organized at different levels, both in the organism and in the larger living
      system within which the organism is subsumed. This view might not only help to
      clarify medically unexplained pain syndromes, but virtually every subjective
      complaint, both with and without recognized physiopathology.

PMID- 12004949
TI  - Stop that! Inhibition, sensitization, and their neurovisceral concomitants.
AB  - There is increasing evidence that the behavior of living systems can be
      conceptualized as a self-organizing dynamical system. Moreover, evidence suggests
      that inhibitory processes give these systems the flexibility that is necessary
      for efficient functioning in the face of changing environmental demands. The
      process of sensitization can be conceived as a breakdown of inhibitory neural
      processes that can lead to maladaptive, perseverative behavior. In this paper we
      describe a model of inhibition and sensitization from a dynamical systems
      perspective. We show that inhibition is important for adaptive behavior across a
      number of levels of system functioning. Using our work on attention, emotion, and
      anxiety disorders we show the importance of both central - for example gamma
      aminobutyric acid (GABA)-ergic - and peripheral - for example heart rate
      variability (HRV) - inhibitory processes and how they may be linked by a network
      of neural structures that guide the organism from one state of relative stability
      to another.

PMID- 12004950
TI  - Negative affect and sensitization to pain.
AB  - Pain usually has a strong negative affective component, which is believed to
      modulate pain perception. After reviewing theories on the link between negative
      affect and pain, mechanisms are discussed by which negative affect may either
      increase or inhibit pain. Possible pain-inhibiting mechanisms are endogenous
      opioid release, blood pressure reactivity, and distraction of attention; possible
      pain-increasing mechanisms are autonomic and muscular reactivity, misattribution
      of arousal, hypervigilance to pain, worrying, and avoidance behavior. It is
      emphasized that each of these mechanisms can be very adaptive in acute pain
      situations to prevent injury and promote recovery. In chronic pain, however,
      ongoing physiological arousal and hypervigilance to pain, induced or magnified by
      negative affect, may cause sensitization to pain. Furthermore, worrying about
      pain and avoidance of pain-inducing activities may increase negative affect,
      ypervigilance, and functional disability. It is argued that, in the long run,
      pain-related negative affect has sensitizing and disabling effects.

PMID- 12004951
TI  - Childhood experience of illness as a risk factor for medically unexplained
      symptoms.
AB  - Clinical experience suggests that a high proportion of patients with medically
      unexplained symptoms or somatoform disorders give histories of adverse childhood
      experiences. Previous work has reported that both personal and family experience
      of illness may be associated with later unexplained symptoms in the individual.
      Most of this research is subject to recall bias. This review explores data from
      the UK Medical Research Council National Survey of Health and Development, a
      population-based birth cohort study. The main finding of this work is that
      childhood experience of illness in parents is an independent risk factor for
      later unexplained symptoms. Personal experience of illness has a more complicated
      relationship. There is no evidence that severe physical disease in childhood is
      associated with later unexplained symptoms, but common childhood unexplained
      symptoms are predictors of symptoms in adulthood.

PMID- 12004952
TI  - Learning subjective health complaints.
AB  - Symptom episodes often show a spatio-temporal structure, that is, they occur in a
      specific context for a certain duration. Repeated experiences may therefore be
      construed as associative learning trials, in which context elements are turned
      into predictive cues, triggering anticipatory processes conducive to subjective
      health complaints. A series of experiments, using inhalations of air enriched
      with CO2 and external (odors) or internal (mental images) stimuli as cues, is
      discussed to show that subjective health complaints may occur upon presenting the
      cue alone. Learned symptoms may be unrelated to bodily responses and easily
      generalize to new related cues. Better learning occurs to cues with a negative
      affective valence and in participants scoring high for negative affectivity. Our
      findings are relevant to the understanding of medically unexplained
      ("functional") syndromes and the poor relationship between objective and
      subjective health indicators in general.

PMID- 12004953
TI  - Cellular memory in spinal nociceptive circuitry.
AB  - Besides transmitting and processing, neurons may also store information for
      prolonged periods of time (e.g. by use-dependent change in synaptic strength). In
      1966 long-term potentiation (LTP) of synaptic transmission was discovered in the
      hippocampus, an area implicated in learning and memory. Recent studies show that
      similar mechanisms apply to pain pathways, at least in the spinal cord, and may
      account for some forms of clinical problems like hyperalgesia, allodynia, and
      deafferentation pain states, such as phantom pain. In this review, we briefly
      summarize key aspects of synaptic plasticity known from the brain and in the
      spinal cord. Then we describe and discuss related changes in spinal nociceptive
      neurons based on results from our own laboratory.

PMID- 12004954
TI  - Sensitization as a mechanism for multiple chemical sensitivity: relationship to
      evolutionary theory.
AB  - Multiple chemical sensitivity (MCS) is a disorder in humans attributed to prior
      chemical exposure. Sensitization is an amplification of neuronal responsiveness
      that elicits increased behavioral responding to stimuli, and occurs in a recently
      developed rat model of MCS. Rats were exposed to repeated formaldehyde (Form) and
      their response in three behavioral tests, including locomotor activity after a
      cocaine challenge, conditioned fear, and behavioral avoidance of Form, was
      assessed. In all three tests, rats demonstrated sensitized behaviors, implicating
      amplified responding within specific limbic brain regions. Evolutionary theory in
      the context of MCS specifies how the behavioral strategies of those with MCS are
      consistent with the notion that their self-perceived sense of survival and
      reproductive fitness may be threatened by chemical exposures. This behavior may
      be mediated by the same limbic brain regions that become sensitized after
      repeated chemical exposure in animals.

PMID- 12004955
TI  - Personality, mental distress, and risk perception in subjects with multiple
      chemical sensitivity and toxic encephalopathy.
AB  - Personality, mental distress, and risk perception were assessed in (a) cases of
      multiple chemical sensitivity (MCS; n = 17), (b) chemically intolerant toxic
      encephalopathy cases (TE), type 2A (n = 31) and 2B (n = 26), and (c) healthy
      referents (n = 200). MCS cases showed elevated mental distress scores on the
      Depression, Interpersonal Sensitivity, Global Severity Index, and Somatization
      scales in the Symptom Checklist 90 (SCL-90). In the Karolinska Scales of
      Personality (KSP) the MCS group showed an elevation only on the Psychasthenia
      scale. Both TE groups showed elevations across the KSP anxiety scales Muscular
      Tension, Psychasthenia, and Somatic Anxiety. TE type 2B subjects also showed
      elevations on the Irritability and Indirect Aggression scales. However, neither
      MCS nor TE groups showed deviating personality characteristics in the Meta
      Contrast Technique test. Similarly, none of the groups deviated from referents in
      a risk perception inventory.

PMID- 12004956
TI  - Somatization, sensitization, and functional dyspepsia.
AB  - Functional dysepsia (FD) is defined as persistent or recurrent pain or discomfort
      centered in the upper abdomen without evidence of organic disease likely to
      explain the symptoms. Visceral hypersensitivity, motor dysfunction, and impaired
      gastric accommodation are found in some patients with FD, and psychological
      factors like chronic stress, attention and perception bias are also likely to
      play a part in the symptom formation. There is considerable overlap of non
      specific symptoms like fatigue, headache, abdominal discomfort, muscle pain, and
      sleep disturbance in patients with different functional disorders, in this
      article exemplified by FD, fibromyalgia, and chronic fatigue syndrome. This
      overlap of symptoms indicates a common underlying sensitization process, leading
      to somatization.

PMID- 12004957
TI  - The effect of sensitization and coping style on post-traumatic stress symptoms
      and quality of life: two longitudinal studies.
AB  - The present study investigated the effects of multiple trauma exposure and coping
      style on post-traumatic stress symptoms and quality of life. It was hypothesized
      that sensitization would occur in subjects repeatedly exposed to life-threatening
      situations (study 1), and different coping styles would act as a resilience or
      facilitating factor in symptom development (study 2). The results showed that the
      single-exposure group revealed a decrease in trauma specific stress reactions
      from three weeks to four months, with a persistent reduction at 12-month follow
      up, while the repeated-exposure group showed an increase in symptom reporting
      over the 12-month period. The same pattern emerged for perceived quality of life
      measured by the General Health Questionnaire (GHQ-30). The second study revealed
      a correlation between scores on avoidant-focused coping style and the Impact of
      Event Scale-avoidance dimension, Post-traumatic Symptom Scale and GHQ-30.
      Furthermore, only subjects with a dominant coping style of emotion-focused or
      task-focused coping showed a reduction in trauma-specific symptom scores over
      time.

PMID- 12004958
TI  - Sensitization and subjective health complaints.
AB  - Why is it that some of us have more pain, more fatigue, and more gastrointestinal
      trouble than others? Is it possible that there are brain mechanisms and
      psychological mechanisms that make some people sensitized to specific complaints?
      In this concluding paper we review the historical and theoretical background,
      discuss the evidence and theoretical positions in the contributions, and draw
      some conclusions. Traditional psychosomatic models had less predictive value and
      less therapeutic importance than what was hoped for. The main problem with these
      models was the lack of a pathophysiological explanation for why psychological
      problems could be related to somatic disease. Sustained arousal or "allostatic
      load" offers more plausible and acceptable mechanisms for pathology, and, to some
      extent, for sensitization and illness. The combination of cognitive psychology
      and neurophysiology offers a model for somatic pathology, and, perhaps more
      important, also for the understanding of subjective complaints and illness.

PMID- 12004959
TI  - Gene expression and larval evolution: changing roles of distal-less and
      orthodenticle in echinoderm larvae.
AB  - We describe the expression of the homeobox genes orthodenticle (Otx) and distal
      less (Dlx) during the larval development of seven species representing three
      classes of echinoderms: Holothuroidea, Asteroidea, and Echinoidea. Several
      expression domains are conserved between species within a single class, including
      Dlx expression within the brachiolar arms of asteroid larvae and Otx expression
      within the ciliated bands of holothuroid larvae. Some expression domains are
      apparently conserved between classes, such as the expression of Dlx within the
      hydrocoel (left mesocoel) in all three classes. However, several substantial
      differences in expression domains among taxa were also evident for both genes.
      Some autapomorphic (unique derived) features of gene expression are
      phylogenetically associated with autapomorphic structures, such as Dlx expression
      within the invaginating rudiment of euechinoids. Other autapomorphic gene
      expression domains are associated with evolutionary shifts in life history from
      feeding to nonfeeding larval development, such as Otx expression within the
      ciliated bands of a nonfeeding holothuroid larva. Similar associations between
      evolutionary changes in morphology and life history mode with changes in
      regulatory gene expression have also been observed in arthropods, urochordates,
      and chordates. We predict that recruitment of regulatory genes to a new
      developmental role is commonly associated with evolutionary changes in morphology
      and may be particularly common in clades with complex life cycles and diversity
      of life history modes. Caution should be used when making generalizations about
      gene expression and function based on a single species, which may not accurately
      reflect developmental processes and life histories of the phyla to which it
      belongs.

PMID- 12004960
TI  - Starting from fins: parallelism in the evolution of limbs and genitalia: the fin
      to-genitalia transition.
AB  - Organizers of the symposium Starting from Fins: Parallelism in the Evolution of
      Limbs and Genitalia intended it 1) to begin debates and discussions about
      parallelism, serial homology and transitions in development, as well as evolution
      of gene function and theories of origins and 2) to examine closely the potential
      significance of serial homology in understanding the evolution of morphology.
      This issue of Evolution and Development focuses on unpaired fin to genitalia
      transitions; the July-August issue will focus on paired fins to limbs, revisit
      the issues raised in the symposium, and point to future directions. Minelli's
      opening presentation introduced the central theme of the symposium by suggesting
      that body appendages such as arthropod and vertebrate limbs, chordate tails and
      external genitalia are evolutionarily divergent duplicates (paramorphs) of the
      main body axis. Suzuki's and Podlasek's presentations focused on the development
      of mammalian genitalia. Suzuki presented Suzuki et al investigations of the role
      of fibroblast growth factor (Fgf) and Sonic hedgehog (Shh) as signaling molecules
      during murine external genitalia formation, and Podlasek presented Podlasek et al
      investigations to elucidate a rudimentary pathway of essential developmental
      genes and transcriptional regulators such as Hox genes, Sonic hedgehog (Shh), and
      Bone morphogenetic proteins 2 and 4 (BMP-2; BMP-4), found in the limb.
      Discussions and questions emerging from the symposium point to the need to
      recognize that claims of phylogenetic cause must be based on something more than
      similarities; research must focus on the extent to which comparisons can be taken
      as well as on the evolutionary significance of similarities.

PMID- 12004961
TI  - Homology, limbs, and genitalia.
AB  - Similarities in genetic control between the main body axis and its appendages
      have been generally explained in terms of genetic co-option. In particular,
      arthropod and vertebrate appendages have been explained to invoke a common
      ancestor already provided with patterned body outgrowths or independent
      recruitment in limb patterning of genes or genetic cassettes originally used for
      purposes other than axis patterning. An alternative explanation is that body
      appendages, including genitalia, are evolutionarily divergent duplicates
      (paramorphs) of the main body axis. However, are all metazoan limbs and genitalia
      homologous? The concept of body appendages as paramorphs of the main body axis
      eliminates the requirement for the last common ancestor of limb-bearing animals
      to have been provided with limbs. Moreover, the possibility for an animal to
      express complex organs ectopically demonstrates that positional and special
      homology may be ontogenetically and evolutionarily uncoupled. To assess the
      homology of animal genitalia, we need to take into account three different sets
      of mechanisms, all contributing to their positional and/or special homology and
      respectively involved (1) in the patterning of themain body axis, (2) in axis
      duplication, followed by limb patterning mechanisms diverging away from those
      still patterning the main body axis (axis paramorphism), and (3) in controlling
      the specification of sexual/genital features, which often, but not necessarily,
      come into play by modifying already developed and patterned body appendages. This
      analysis demonstrates that a combinatorial approach to homology helps
      disentangling phylogenetic and ontogenetic layers of homology.

PMID- 12004962
TI  - Embryonic development of mouse external genitalia: insights into a unique mode of
      organogenesis.
AB  - The mammalian external genitalia are specialized appendages for efficient
      copulation, internal fertilization and display marked morphological variation
      among species. In this paper, we described the embryonic development of mouse
      genital tubercle (GT), an anlage of the external genitalia utilizing the scanning
      electron microscope (SEM) analysis. It has been shown that the Distal Urethral
      Epithelium (DUE) may fulfill an essential role in the outgrowth control of the
      GT. Our present SEM analysis revealed a small distal protrusion at the tip of the
      GT of normal embryos as well as some morphological differences between male and
      female embryonic external genitalia. Previous analysis shows that the teratogenic
      dose of Retinoic Acid (RA) induces a drastic marformation of the urethral plate,
      but not gross abnormalities for GT outgrowth. Interestingly, a small distal
      protrusion at the tip of GT was clearly observed also after RA treatement.
      Furthermore, we showed that treatment with anti-androgen flutamide resulted in
      the demasculinization of the GT in males. The unique character of GT development
      and the sexual dimorphism are discussed.

PMID- 12004963
TI  - Posterior Hox gene expression in developing genitalia.

PMID- 12004964
TI  - The g-value paradox.

PMID- 12004965
TI  - Expression of a homologue of the fushi tarazu (ftz) gene in a cirripede
      crustacean.
AB  - In Metazoa, Hox genes control the identity of the body parts along the
      anteroposterior axis. In addition to this homeotic function, these genes are
      characterized by two conserved features: They are clustered in the genome, and
      they contain a particular sequence, the homeobox, encoding a DNA-binding domain.
      Analysis of Hox homeobox sequences suggests that the Hox cluster emerged early in
      Metazoa and then underwent gene duplication events. In arthropods, the Hox
      cluster contains eight genes with a homeotic function and two other Hox-like
      genes, zerknullt (zen)/Hox3 and fushi tarazu (ftz). In insects, these two genes
      have lost their homeotic function but have acquired new functions in
      embryogenesis. In contrast, in chelicerates, these genes are expressed in a Hox
      like pattern, which suggests that they have conserved their ancestral homeotic
      function. We describe here the characterization of Diva, the homologue of ftz in
      the cirripede crustacean Sacculina carcini. Diva is located in the Hox cluster,
      in the same position as the ftz genes of insects, and is not expressed in a Hox
      like pattern. Instead, it is expressed exclusively in the central nervous system.
      Such a neurogenic expression of ftz has been also described in insects. This
      study, which provides the first information about the Hoxcluster in Crustacea,
      reveals that it may not be much smaller than the insect cluster. Study of the
      Diva expression pattern suggests that the arthropod ftz gene has lost its
      ancestral homeotic function after the divergence of the Crustacea/Hexapoda clade
      from other arthropod clades. In contrast, the function of ftz during neurogenesis
      is well conserved in insects and crustaceans.

PMID- 12004966
TI  - Ancient ontogenies: larval development of the Lower Cretaceous anuran Shomronella
      jordanica (Amphibia: Pipoidea).
AB  - The Lower Cretaceous anuran Shomronella jordanica (Pipoidea) is represented by an
      assemblage of nearly 300 tadpoles of different ages. The size of the assemblage
      allows a reconstruction of the larval ontogeny of this species. We describe the
      ossification sequence and growth rates of S. jordanica and present
      reconstructions of tadpoles at different stages. The ontogeny of the species
      seems to be similar to that of extant pipids in many aspects. Larvae are similar
      in shape and size to those of Xenopus laevis but lack the anterior barbels that
      are typical for all extant pipids. The ossification sequence is closer to that of
      pipids than to that of other anurans. We present evidence that suggests that this
      species was terrestrial as an adult, and we discuss the implications of these
      data for the evolution of anuran development.

PMID- 12004967
TI  - The development and evolution of insect mouthparts as revealed by the expression
      patterns of gnathocephalic genes.
AB  - To understand better both the development and evolution of insect mouthparts, we
      have compared the expression pattern of several developmentally important genes
      in insects with either mandibulate or stylate-haustellate mouthparts.
      Specifically, we examined the expression of the proboscipedia (pb) and Distal
      less (Dll) gene products as well as three regulators of pb, Sex combs reduced
      (Scr), Deformed (Dfd), and cap 'n' collar (cnc). These genes are known to control
      the identity of cells in the gnathal segments of Drosophila melanogaster and
      would appear to have similar conserved functions in other insects. Together we
      have made an atlas of gene expression in the heads of three insects: Thermobia
      domestica and Acheta domestica, which likely exemplify the mandibulate mouthparts
      present in the common insect ancestor, and Oncopeltus fasciatus, which has
      piercing-sucking mouth parts that are typical of the Hemiptera. At the earliest
      stages of embryogenesis, only the expression of pb was found to differ
      dramatically between Oncopeltus and the other insects examined, although
      significant differences were observed later in development. This difference in pb
      expression reflects an apparent divergence in the specification of gnathal
      identity between mandibulate and stylate-haustellate mouthparts, which may result
      from a "phylogenetic homeosis" that occurred during the evolution of the
      Hemiptera.

PMID- 12004968
TI  - Theoretical understanding and methodological challenges in accessibility
      assessments, focusing the environmental component: an example from travel chains
      in urban public bus transport.
AB  - PURPOSE: In order to increase the theoretical understanding of the concept of
      accessibility, this paper reports the results from an exploration of
      methodological difficulties inherent in systematic accessibility assessments of
      single persons' travel chains in urban public bus transport. In addition, Special
      Transport Service (STS) travellers' perception of environmental demands in public
      transport are reported. METHODS: This study was designed to explore the
      environmental component in accessibility problems systematically. Twenty persons
      entitled to STS were recruited in order to travel by low-floor bus, Service Route
      Traffic (SRT) or STS. Two different methods were chosen. Critical incidents were
      collected during participant observation, and by means of a pilot instrument
      based on the Enabler Concept independent environmental assessments were
      performed. RESULTS: Not all environmental details registered during the
      participant observations were in agreement with the independent environmental
      assessment, and different reasons for the disagreements were reported. In
      addition, participants travelling by STS gave information about what hindered
      them from using conventional public transport. CONCLUSIONS: The theoretical
      understanding behind accessibility assessments has benefited from the
      methodological challenges mapped out in this study. In order to interpret
      accessibility, the individual perspective as well as the population perspective
      are necessary, which means that complementary methods are needed.

PMID- 12004969
TI  - Repeatability of standardized tests of functional impairment and well-being in
      older people in a rehabilitation setting.
AB  - PURPOSE: The aim of this study was to establish the repeatability of standardized
      tests of vision (Snellen chart testing), hearing (whispered voice test),
      communication (Frenchay aphasia screening test), loneliness (UCLA loneliness
      scale), morale (Philadelphia geriatric centre morale scale), and a
      multidimensional instrument (EASY-care) when used in a rehabilitation setting.
      METHOD: The tests were administered by a research nurse to 50 older subjects
      attending a day rehabilitation unit, with repeat administration one or two weeks
      later by a nurse on the unit. Kappa statistics were used for level of agreement
      for categorized data and interclass correlation coefficient were used for data
      based on scores. RESULTS: Moderate repeatability for Snellen chart testing.
      whispered voice test; good to excellent for the FAST, UCLA loneliness scale and
      Philadelphia geriatric centre morale scale. Moderate to very good repeatability
      for all EASY-care items except communication, feeding, use of telephone and
      cognitive impairment, which had poor spread of data. CONCLUSIONS: Poor
      repeatability for commonly used tests of vision and hearing is worrying, whereas
      the positive results for the other tests will increase confidence in using them
      more in routine practice.

PMID- 12004970
TI  - Dutch adaptation and content validity of the 'Pediatric Evaluation Of Disability
      Inventory (PEDI)'.
AB  - PURPOSE: To adapt the American PEDI into a Dutch version, and to establish the
      content validity of this pediatric functional status instrument. METHODS: The
      adaptation process was based on current scientific guidelines in the field of
      cross-cultural research. Thirty-one allied health professionals completed a
      validity questionnaire for the content validity study. RESULTS: The topic
      'bicycling' was added to the questionnaire, and adaptations of the text were made
      without losing the content of the original PEDI. At least 81% of the respondents
      rated that the most important facets in examining functional status in childhood
      were represented in the Dutch PEDI. Eighty-seven per cent and 71% of the
      respondents rated that the PEDI is feasible for discriminative purposes and
      evaluative purposes, respectively. CONCLUSION: The expert panel confirmed the
      functional content and feasibility of the Dutch PEDI for pediatric rehabilitation
      outcome measurement.

PMID- 12004971
TI  - Predictors of quality of life following stroke.
AB  - PURPOSE: To determine the factors predicting quality of life during the course of
      rehabilitation following stroke. METHOD: Two hundred and fifteen stroke patients
      aged 41 93 were studied over a period of three months. Measurement of quality of
      life, functional ability, social support. demographic and treatment data were
      taken on admission to the rehabilitation hospital, at two weeks and three months.
      The instruments used were the Sickness Impact Profile (SIP), the Modified Barthel
      Index (MBI) and The Social Support Questionnaire, short form (SSQ6). RESULTS:
      Length of stay, previous stroke, functional ability and social support were found
      to be significantly correlated with quality of life. Stepwise multiple regression
      analysis indicated that functional ability, psychological and physical SIP
      dimensions, social support satisfaction at two weeks and previous stroke
      explained 47% of the variance in sickness impact at three months following
      stroke. The factors predicting 53% of the variance in sickness impact at two
      weeks were baseline functional ability, psychological and physical SIP.
      CONCLUSIONS: The findings indicate that both psychosocial and physical factors
      are important in predicting quality of life in stroke rehabilitation. Determining
      such predictors at an early stage will help to guide clinical decisions
      throughout rehabilitation.

PMID- 12004972
TI  - Reliability of the Home Falls and Accidents Screening Tool (HOME FAST) for
      identifying older people at increased risk of falls.
AB  - PURPOSE: The Home Falls and Accidents Screening Tool (HOME FAST) was designed as
      part of a comprehensive health assessment instrument to measure falls risk for
      older people within their home environment. This paper describes the evaluation
      of the inter-rater reliability of the HOME FAST. METHOD: Forty home visits were
      undertaken, in urban and rural settings of the UK, by pairs of raters, one of
      whom was an expert rater. Occupational therapists, occupational therapy
      assistants and a social worker rated each home using the HOME FAST concurrently
      with an expert rater. The kappa statistic was used to determine the degree of
      agreement between pairs of raters. RESULTS: The overall kappa value for the
      checklist was 0.62, indicating a fair to good level of agreement between raters.
      'Hazardous outside paths' was the only item that demonstrated poor agreement
      (kappa = 0.30). The expert rater consistently identified more hazards than the
      other raters, and the level of agreement was stable between raters irrespective
      of the number of hazards present in the homes visited. CONCLUSIONS: Definitions
      of non-applicable household features and improving the objectivity of the
      operational definitions for recognizing hazards that demand more qualitative
      judgements will enhance the reliability of the HOME FAST.

PMID- 12004973
TI  - A study of the gait characteristics of patients with chronic osteoarthritis of
      the knee.
AB  - PURPOSE: There is scant information at present on the effects of severe
      osteoarthritis (OA) of the knee joint on gait. In the present study the kinematic
      and kinetic parameters of gait and the pattern of activation of four lower limb
      muscles were examined during walking at a self-selected pace on level ground. The
      spatiotemporal parameters of gait were also computed. METHODS: Measurements were
      made using a three-dimensional optico-electronic motion analysis system
      integrated with a force plate and telemetered electromyography. RESULTS: Fifty
      eight patients with severe OA of the knee and 25 age-matched healthy control
      subjects were examined. Patients demonstrated a significantly reduced walking
      speed, shorter stride length and a more prolonged stance phase of the gait cycle
      compared with the control subjects. They also had less range of motion at the
      hip, knee and ankle, joints and generated less moments and powers at the ankle
      and more moments at the knee than the control group. The differences were
      statistically significant for all parameters except the degree of ankle plantar
      flexion in stance. Activation of the rectus femoris muscle was prolonged in the
      patients group. CONCLUSIONS: It is concluded that the observed gait abnormalities
      were due to instability of the knee joint in stance. This may have important
      clinical implications for the rehabilitation of patients with severe OA of the
      knee.

PMID- 12004974
TI  - Application of the International Classification of Functioning, Disability and
      Health (ICF) in clinical practice.

PMID- 12004975
TI  - Simeonsson et al. on the participation of students with disabilities in school
      activities.

PMID- 12004976
TI  - Large-scale mercury variations in Lake Vanern (Sweden) 1974-98.
AB  - Lake Vanern, the largest lake in Sweden, has been seriously contaminated with
      mercury during the 20th century. In the 1970's and 80's the direct load, mainly
      from a chlor-alkali industry in the area, of mercury was drastically reduced as a
      response to new legislation, from three to five tons down to between five and ten
      kg yr(-1). Large amounts of the disposed pollutant have accumulated in the
      sediments. The question posed in this work is now, is the effect of the drastic
      load reduction after more than two decades visible in the sediments? The question
      is relevant as large areas still are blacklisted for fishing, but also as a
      follow-up of a major remedy action. The lake also serves as a freshwater
      reservoir for even Sweden's second largest city. This work synthesises and
      compares data of mercury in the sediments from three major field programs, in
      1974, 1984 and 1998. The interest is focused on both spatial heterogeneity and
      temporal trends. In 1974, the surface concentrations are significantly higher
      than in subsequent surveys. Significant differences are also found between 1984
      and 1998. Significant spatial differences within the lake are found for
      respective year. The most contaminated area is located in the north, close to the
      major point source (a former chlor-alkali industry). This is also the area with
      the largest improvement, as a direct response to the reduction in load. Further
      from the outlet, the recovery is more affected by burial and transport processes
      out into the deeper basins.

PMID- 12004977
TI  - Vitellogenin induction in Cyprinus carpio treated with 17beta-estradiol and 4
      nonylphenol.
AB  - The aim of the present study was to demonstrate induction of vitellogenin in the
      common carp (Cyprinus carpio) as a biomarker for monitoring freshwater
      ecosystems. Sexually undifferentiated specimens of common carp were treated
      experimentally with 17beta-estradiol and increasing doses of 4-nonylphenol and
      levels of plasma Vtg were measured in order to: 1) validate an ELISA assay for
      plasma Vtg in the common carp using the polyclonal rabbit anti-salmon Vtg
      antibody AA1 (Biosense, Norway); 2) check the sensitivity of carp juveniles in
      producing Vtg in response to estrogen stimulation. The group treated with 17beta
      estradiol showed high induction (156%) with respect to controls, also groups
      treated with 4-nonylphenol showed induction of Vtg. The group treated with 100 mg
      kg(-1) b.wt showed an induction of 61%. A statistically significant correlation
      was found between dose and response. This preliminary study demonstrate a
      response to the ELISA assay for Vtg in the common carp using rabbit anti-salmon
      antibody AA1. With further evidence the tested biomarker might be proposed for
      large scale monitoring of estrogenic effects caused by pollution in urban and
      industrial effluents.

PMID- 12004978
TI  - Occurrence of Cryptosporidium oocysts in sewage effluents and correlation with
      microbial, chemical and physical water variables.
AB  - Contaminated water are recognized as a potential source of Cryptosporidium
      oocysts. In Italy studies on the environmental spread of the parasite are still
      scarce even if a high frequency of serological responses could suggest high rates
      of endemic Cryptosporidium infections. In this investigation the occurrence of
      the parasite in water samples from a municipal wastewater treatment plant was
      monitored with the aim to evaluate possible correlation between oocysts and
      bacterial indicators, pathogens and physico-chemical parameters using a
      multivariate analysis. Data collected showed high numbers of oocysts, with a high
      percentage of positive samples and a significant correlation with pH, redox
      potential and total organic carbon. No correlation was found between
      Cryptosporidium concentration and that of the other microrganisms. The results,
      through a probing statistical analysis, show that none of the selected
      microrganisms was a reliable predictor of the presence of the parasite.

PMID- 12004979
TI  - The ecological condition of south Florida estuaries.
AB  - An assessment of the ecological condition of south Florida estuaries based on
      regional probabilistic monitoring was conducted during the summer of 1995.
      Samples and data were collected on water and sediment quality, benthos, and fish
      tissue contaminants. Elevated concentrations of metals and pesticides were
      measured in both sediments and fish tissue with some exceedances of guidance
      values. Bottom dissolved oxygen levels over 23-37% of the area were below state
      criteria. Eighty-eight percent of surface waters had greater than 10% penetration
      of ambient light to a depth of 1.0 m. Nine percent of the area studied in South
      Florida exhibited degraded biology and impaired use based on a calculated index
      of ecological condition. Using the probability-based monitoring design, useful
      information of this type can be provided to resource managers regarding estuarine
      condition on a regional scale.

PMID- 12004980
TI  - Evaluation of data quality in lichen biomonitoring studies: the Italian
      experience.
AB  - A total of 65 operators involved in lichen mapping studies in central and
      northwestern Italy underwent quality control tests during five lichen
      biomonitoring workshops organized between 1999 and 2000. The results showed that
      75% quantitative accuracy and 90% quantitative precision can be regarded as
      satisfactory levels for lichen biodiversity data; 65% proved to be sufficient for
      accuracy of taxonomic identification in the field. Average correct assignment of
      the interpretative naturality/alteration class was only 48.7%. The results
      indicated the need for taxonomic training.

PMID- 12004981
TI  - A new voltammetric method for the simultaneous monitoring of heavy metals in sea
      water, sediments, algae and clams: application to the Goro Bay ecosystem.
AB  - Arsenic(III), selenium(IV), copper(II), lead(II), cadmium(II), zinc(II) have been
      determined in sea water, sediments, algae and clams by differential pulse
      cathodic (DPCSV) and anodic (DPASV) stripping voltammetry. The voltammetric
      measurements are carried out using a conventional three-electrode cell and the
      ammonia-ammonium chloride buffer pH 9.2 as supporting electrolyte. The analytical
      procedure has been verified by the analysis of the standard reference materials
      (Estuarine Sediment BCR- CRM 277, Ulva Lactuca BCR-CRM 279 and Mussel Tissue BCR
      CRM 278). The precision and the accuracy are less than 5%. This procedure is
      utilized for the monitoring of heavy metals in the Po river mouth area (Italy).

PMID- 12004982
TI  - Characterisation of airborne particles collected within and proximal to an
      opencast coalmine: South Wales, U.K.
AB  - Airborne particulate matter has been collected from within, and proximal to, an
      opencast coal mine in south Wales. This work forms the first part of a three year
      project to collect and characterise, then determine the possible toxicology of
      airborne particles in the south Wales region. High-resolution Field Emission SEM
      has shown that the coal mine dusts consist largely of an assemblage of mineral
      grains and vehicle exhaust particles. SEM-EDX has shown that the mineralogical
      make-up of the PM10 is complex, heterogeneous, and constantly changing. These
      findings are supported by analytical TEM-EPXMA. However, patterns can be
      determined relating the mineralogical composition of the airborne particles to
      collection locations and mining activities within the opencast. At our study
      opencast, Park Slip West, quartz, which has known health effects, never exceeded
      30% of the total collection mass, and average levels were much less. Vehicle
      exhaust emissions was the largest source in terms of particle numbers. The mass
      of airborne particulate matter within the pit averaged approximately twice that
      of outside the pit: importantly however, this higher mass was due to relatively
      large, and non-respirable, mineral grains. This study demonstrates that the
      physicochemical and mineralogical characterisation of airborne particles from
      mining and quarrying is essential to quantify the respirable fraction, and to
      identify potentially hazardous components within the PM10.

PMID- 12004983
TI  - Prevalence of selected maternal behaviors and experiences, Pregnancy Risk
      Assessment Monitoring System (PRAMS), 1999.
AB  - PROBLEM/CONDITION: Various maternal behaviors and experiences before, during, and
      after pregnancy (e.g., unintended pregnancy, late entry into prenatal care,
      cigarette smoking, not breast-feeding) are associated with adverse health
      outcomes for both the mother and the infant. Information regarding maternal
      behaviors and experiences is needed to monitor trends, to enhance the
      understanding of the relations between behaviors and health outcomes, to plan and
      evaluate programs, to direct policy decisions, and to monitor progress toward
      Healthy People 2000 and 2010 objectives. REPORTING PERIOD COVERED: This report
      covers data from 1993 through 1999. DESCRIPTION OF SYSTEM: The Pregnancy Risk
      Assessment Monitoring System (PRAMS) is an ongoing, state- and population-based
      surveillance system designed to monitor selected self-reported maternal behaviors
      and experiences that occur before, during, and after pregnancy among women who
      deliver a live-born infant. PRAMS employs a mixed-mode data collection
      methodology; up to three self-administered surveys are mailed to a sample of
      mothers, and nonresponders are followed up with a telephone interview. Self
      reported survey data are linked to selected birth certificate data and weighted
      for sample design, nonresponse, and noncoverage to create annual PRAMS analysis
      data sets. PRAMS generates statewide estimates of various perinatal health topics
      among women delivering a live infant. Data for 1999 from 17 states are examined.
      In addition, trend data are examined for 12 states that had at least 3 years of
      data during 1993-1999. RESULTS: In 1999, the prevalence of unintended pregnancy
      resulting in a live birth ranged from 33.7% to 52% across the 17 states. During
      1993-1999, only one state reported a decreasing trend in the prevalence of
      unintended pregnancy. Women aged <20 years, black women, women with less than or
      equal to a high school education, and women receiving Medicaid were more likely
      to report unintended pregnancy. The prevalence of late or no entry into prenatal
      care ranged from 16.1% to 29.9%. The prevalence of late or no entry into prenatal
      care significantly decreased over time in seven of the 12 states with trend data.
      In general, women aged <20 years, black women, women with less than a high school
      education, and women receiving Medicaid were more likely to report late or no
      entry into prenatal care. The prevalence of smoking during the last 3 months of
      pregnancy ranged from 6.2% to 27.2%, and the prevalence decreased in five states
      from 1993 to 1999. Overall, smoking during the last 3 months of pregnancy was
      associated with younger age (<25 years), non-Hispanic ethnicity, having less than
      or equal to a high school education, receiving Medicaid, and delivering a low
      birthweight infant. The prevalence of physical abuse by a husband or partner
      during pregnancy ranged from 2.1% to 6.3%. No trends were observed for physical
      abuse from 1996 to 1999, the only years for which these data were available.
      Across the 17 states, only Medicaid status was consistently associated with
      experiencing physical abuse during pregnancy. The prevalence of breast-feeding
      initiation ranged from 48% to 89%. Ten of 12 states with trend data reported
      increases in the prevalence of breast-feeding initiation. Overall, women aged <20
      years, women with less than or equal to a high school education, and women
      receiving Medicaid were less likely to breast-feed. The prevalence of breast
      feeding duration for at least 4 weeks ranged from 34.9% to 78.1%. From 1993 to
      1999, increases in levels of breast-feeding for at least 4 weeks were observed in
      eight states. Women aged <25 years, black women, women with less than or equal to
      a high school education, and women receiving Medicaid were generally less likely
      to breast-feed for at least 4 weeks. The prevalence of back sleep position for
      infants ranged from 35.1% to 74.6%. Increases in the use of the back sleep
      position were observed in all 12 states with trend data from 1996 to 1999. Black
      race and having less than or equal to a high school education were consistently
      associated with not using the back sleep position. INTERPRETATION: For
      surveillance during 1993-1999, the majority or all states observed increases in
      breast-feeding initiation, breast-feeding for at least 4 weeks, and back sleep
      position. Approximately one half of the states observed decreases for late or no
      entry into prenatal care and smoking during the last 3 months of pregnancy.
      Little or no progress was observed in the prevalence of unintended pregnancy or
      physical abuse during pregnancy. With few exceptions, the 17 states failed to
      meet the Healthy People 2000 objectives for the seven reported behaviors in 1999.
      Certain de

PMID- 12004984
TI  - Fixed obstructive lung disease in workers at a microwave popcorn factory-
      Missouri, 2000-2002.
AB  - In May 2000, an occupational medicine physician contacted the Missouri Department
      of Health and Senior Services (MoDHSS) to report eight cases of fixed obstructive
      lung disease in former workers of a microwave popcorn factory. Four of the
      patients were on lung transplant lists. All eight had a respiratory illness
      resembling bronchiolitis obliterans with symptoms of cough and dyspnea on
      exertion, had worked at the same popcorn factory (factory A) at some time during
      1992-2000, and had spirometric test results that were lower than normal for both
      FEV1 (forced expiratory volume in 1 second) and FEV1/FVC (forced vital capacity)
      ratio. Employment durations ranged from 8 months to 9 years. MoDHSS requested
      assistance from CDC's National Institute for Occupational Safety and Health in
      evaluating factory A for respiratory hazards to workers. This report summarizes
      the epidemiologic findings motivating the technical assistance request and
      preliminary results. The findings of this investigation indicate that workers
      exposed to flavorings at microwave popcorn factories are at risk for developing
      fixed obstructive lung disease. Public health authorities, employers, and health
      care providers are collaborating to prevent obstructive lung disease in popcorn
      factory workers.

PMID- 12004985
TI  - Factors associated with pilot fatalities in work-related aircraft crashes-
      Alaska, 1990-1999.
AB  - Despite its large geographic area, Alaska has only 12,200 miles of public roads,
      and 90% of the state's communities are not connected to a highway system.
      Commuter and air-taxi flights are essential for transportation of passengers and
      delivery of goods, services, and mail to outlying communities (Figure 1). Because
      of the substantial progress in decreasing fatalities in the fishing and logging
      industries, aviation crashes are the leading cause of occupational death in
      Alaska. During 1990-1999, aircraft crashes in Alaska caused 107 deaths among
      workers classified as civilian pilots. This is equivalent to 410 fatalities per
      100,000 pilots each year, approximately five times the death rate for all U.S.
      pilots and approximately 100 times the death rate for all U.S. workers. As part
      of a collaborative aviation safety initiative that CDC's National Institute for
      Occupational Safety and Health (NIOSH) is implementing with the Federal Aviation
      Administration (FAA), the National Transportation Safety Board (NTSB), and the
      National Weather Service, CDC analyzed data from NTSB crash reports to determine
      factors associated with pilot fatalities in work-related aviation crashes in
      Alaska. This report summarizes the result of this analysis, which found that the
      following factors were associated with pilot fatalities: crashes involving a post
      crash fire, flights in darkness or weather conditions requiring instrument use,
      crashes occurring away from an airport, and crashes in which the pilot was not
      using a shoulder restraint. Additional pilot training, improved fuel systems that
      are less likely to ignite in crashes, and company policies that discourage flying
      in poor weather conditions might help decrease pilot fatalities. More detailed
      analyses of crash data, collaborations with aircraft operators to improve safety,
      and evaluation of new technologies are needed.

PMID- 12004986
TI  - Respiratory illness in workers exposed to metalworking fluid contaminated with
      nontuberculous mycobacteria--Ohio, 2001.
AB  - In January 2001, three machinists at an automobile brake manufacturing facility
      in Ohio (plant A) were hospitalized with respiratory illness characterized by
      dyspnea, cough, fatigue, weight loss, hypoxia, and pulmonary infiltrates.
      Hypersensitivity pneumonitis (HP) was diagnosed in all three workers. In March
      2001, additional employees began seeking medical attention for respiratory and
      systemic symptoms. In May 2001, union and management representatives requested
      assistance from CDC's National Institute for Occupational Safety and Health
      (NIOSH) in determining the cause of the illnesses and preventing further illness
      in employees. This report describes two case reports and the preliminary results
      of the ongoing investigation, which found that exposure to aerosolized
      nontuberculous mycobacteria (NTM) might be contributing to the observed
      respiratory illnesses in this manufacturing facility. Clinicians and public
      health professionals should be alert to the variable presentation of occupational
      respiratory disease that might occur in workers in the machining industry.

PMID- 12004987
TI  - Dorothy Hodgkin--1964 Nobel laureate for work on vitamin B12.

PMID- 12004988
TI  - Inferring long QT1 genotype based on a simple epinephrine infusion protocol: from
      the bedside to the bench and back.

PMID- 12004989
TI  - Past, present, and future of endoscopic retrograde cholangiopancreatography:
      perspectives on the National Institutes of Health consensus conference.

PMID- 12004990
TI  - Epinephrine-induced QT interval prolongation: a gene-specific paradoxical
      response in congenital long QT syndrome.
AB  - OBJECTIVE: To determine the effect of epinephrine on the QT interval in patients
      with genotyped long QT syndrome (LQTS). PATIENTS AND METHODS: Between May 1999
      and April 2001, 37 patients (24 females) with genotyped LQTS (19 LQT1, 15 LQT2, 3
      LQT3, mean age, 27 years; range, 10-53 years) from 21 different kindreds and 27
      (16 females) controls (mean age, 31 years; range, 13-45 years) were studied at
      baseline and during gradually increasing doses of intravenous epinephrine
      infusion (0.05, 0.1, 0.2, and 0.3 microg x k(-1) x min(-1)). The 12-lead
      electrocardiogram was monitored continuously, and heart rate, QT, and corrected
      QT interval (QTc) were measured during each study stage. RESULTS: There was no
      significant difference in resting heart rate or chronotropic response to
      epinephrine between LQTS patients and controls. The mean +/- SD baseline QTc was
      greater in LQTS patients (500+/-68 ms) than in controls (436+/-19 ms, P<.001).
      However, 9 (47%) of 19 KVLQT1-genotyped LQT1 patients had a nondiagnostic resting
      QTc (<460 milliseconds), whereas 11 (41%) of 27 controls had a resting QTc higher
      than 440 milliseconds. During epinephrine infusion, every LQT1 patient manifested
      prolongation of the QT interval (paradoxical response), whereas healthy controls
      and patients with either LQT2 or LQT3 tended to have shortened QT intervals
      (P<.001). The maximum mean +/- SD change in QT (AQT [epinephrine QT minus
      baseline QT]) was -5+/-47 ms (controls), +94+/-31 ms (LQT1), and -87+/-67 ms
      (LQT2 and LQT3 patients). Of 27 controls, 6 had lengthening of their QT intervals
      (AQT >30 milliseconds) during high-dose epinephrine. Low-dose epinephrine (0.05
      microg x kg(-1) x min(-1)) completely discriminated LQT1 patients (AQT, +82+/-34
      ms) from controls (AQT, -7+/-13 ms; P<.001). Epinephrine-triggered nonsustained
      ventricular tachycardia occurred in 2 patients with LQTS and in 1 control.
      CONCLUSIONS: Epinephrine-induced prolongation of the QT interval appears
      pathognomonic for LQT1. Low-dose epinephrine infusion distinguishes controls from
      patients with concealed LQT1 manifesting an equivocal QTc at rest. Thus,
      epinephrine provocation may help unmask some patients with concealed LQTS and
      strategically direct molecular genetic testing.

PMID- 12004991
TI  - Role of magnetic resonance cholangiopancreatography in patients with suspected
      choledocholithiasis.
AB  - OBJECTIVES: To investigate the diagnostic efficacy of magnetic resonance
      cholangiopancreatography (MRCP) in choledocholithiasis and to determine whether
      use of MRCP may eliminate the need for purely diagnostic endoscopic retrograde
      cholangiopancreatography (ERCP). PATIENTS AND METHODS: A total of 116 patients
      with suspected biliopancreatic pathology were studied prospectively between
      November 1996 and February 1998. Choledocholithiasis was initially suspected in
      61 patients and rated before ERCP and MRCP as being of low, intermediate, or high
      probability based on clinical, laboratory, and/or imaging findings (Cotton
      criteria). RESULTS: The sensitivity of choledocholithiasis diagnosis was 91%,
      with a global efficacy of 90%. The level of duct stone obstruction was visualized
      in all patients. Suprastenotic dilatation also showed a good correlation to ERCP.
      Choledocholithiasis was found in 32 patients (65%) and 3 patients (33%) in the
      high- and intermediate-probability groups, respectively. None of the low
      probability patients had choledocholithiasis. Endoscopic retrograde
      cholangiopancreatography was performed for only a diagnostic (not therapeutic)
      purpose in 3 patients (6%) and 2 patients (22%) of the high- and intermediate
      probability cases, respectively. CONCLUSIONS: Magnetic resonance
      cholangiopancreatography seems to be effective in diagnosing choledocholithiasis.
      It plays a fundamental role in patients with a low or intermediate risk of
      choledocholithiasis, contributing to the avoidance of purely diagnostic ERCP.

PMID- 12004992
TI  - Consecutive 1127 therapeutic echocardiographically guided pericardiocenteses:
      clinical profile, practice patterns, and outcomes spanning 21 years.
AB  - OBJECTIVES: To evaluate consecutive therapeutic echocardiographically (echo)
      guided pericardiocenteses performed at Mayo Clinic, Rochester, Minn, from 1979 to
      2000 and to determine whether patient profiles, practice patterns, and outcomes
      have changed over time. PATIENTS AND METHODS: Consecutive echo-guided
      pericardiocenteses performed between February 1, 1979, and January 31, 2000, for
      treatment of clinically significant pericardial effusions were identified in the
      Mayo Clinic Echocardiographic-guided Pericardiocentesis Registry. The medical
      records of these patients were examined, and a follow-up survey was conducted.
      Clinical profiles, echocardiographic findings, procedural details, and outcomes
      were determined for 3 periods: February 1, 1979, through January 31, 1986;
      February 1, 1986, through January 31, 1993; and February 1, 1993, through January
      31, 2000. RESULTS: During the 21-year study period, 1127 therapeutic echo-guided
      pericardiocenteses were performed in 977 patients. The mean +/- SD age at
      pericardiocentesis increased from 49+/-14 years in period 1 to 57+/-14 years in
      period 3. In recent years, cardiothoracic surgery replaced malignancy as the
      leading cause of an effusion requiring pericardiocentesis and together with
      malignancy and perforation from catheter-based procedures accounted for nearly
      70% of all pericardiocenteses performed. The procedural success rate was 97%
      overall, with a total complication rate of 4.7% (major, 1.2%; minor, 3.5%). These
      rates did not change significantly over time. The use of a pericardial catheter
      for extended drainage increased from 23% in period 1 to 75% in period 3 (P<.001),
      whereas rates of effusion recurrence and pericardial surgery decreased
      significantly (P<.001). CONCLUSIONS: The profile of patients presenting with
      clinically significant pericardial effusion has changed over time. Increasing
      numbers of older patients and those who have undergone cardiothoracic surgery or
      catheter-based procedures develop effusions that can be rapidly, safely, and
      effectively managed with echo-guided pericardiocentesis. Extended drainage with
      use of a pericardial catheter has become standard practice, and concomitantly,
      recurrence rates and need for surgical management have decreased considerably.

PMID- 12004993
TI  - Efficacy and safety of low-dose fluticasone propionate compared with montelukast
      for maintenance treatment of persistent asthma.
AB  - OBJECTIVE: To compare the long-term effects of an inhaled corticosteroid with
      those of a leukotriene modifier on measures of clinical efficacy, subject
      preference, and safety in patients with persistent asthma. PATIENTS AND METHODS:
      Between November 17, 1998, and May 26, 2000, we conducted a multicenter,
      randomized, double-blind, double-dummy, parallel-group study of patients aged 15
      years or older with persistent asthma. The patients were symptomatic while taking
      short-acting beta2-agonists alone and were treated with fluticasone propionate
      (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg/d) for 24
      weeks. Measures of pulmonary function, asthma symptoms, albuterol use, nighttime
      awakenings, physician assessments of efficacy, patient satisfaction, asthma
      related quality of life, and safety were evaluated. RESULTS: A total of 522
      patients were randomized to receive fluticasone or montelukast, and 395 patients
      completed the study. At end point, treatment with fluticasone significantly
      improved pulmonary function, asthma symptom scores, the percentage of symptom
      free days, rescue albuterol use, and the number of nighttime awakenings due to
      asthma when compared with montelukast (P< or = .002, each comparison).
      Significantly more patients were satisfied with fluticasone therapy (83%)
      compared with montelukast therapy (66%) (P<.001), and fluticasone therapy was
      rated as effective by a significantly greater portion of physicians (67%) than
      was montelukast therapy (54%) (P<.001). Treatment with fluticasone significantly
      improved asthma-related quality-of-life measures compared with montelukast (P< or
      =.01). The incidence of asthma exacerbations was similar in the fluticasone (19
      patients, 7%) and montelukast (21 patients, 8%) treatment groups, although
      slightly more patients in the montelukast group were withdrawn from the study
      because of asthma exacerbations (6% vs 4%, respectively). CONCLUSION: Long-term
      treatment with a low dose of inhaled fluticasone is more effective than oral
      montelukast as first-line maintenance therapy for the treatment of persistent
      asthma.

PMID- 12004994
TI  - Effect of differing immunization policies on circulating measles antibody levels
      in US and Canadian children.
AB  - OBJECTIVE: To examine the effect of differing age-at-immunization policies on
      measles antibody levels in US children immunized at the age of 15 months compared
      with Canadian children immunized at the age of 12 months. SUBJECTS AND METHODS:
      Healthy, volunteer US and Canadian children aged 6 to 11 years who had been
      immunized with a single dose of the measles vaccine were enrolled from 1991 to
      1993. Measles antibody was measured with a whole-virus, measles-specific IgG
      enzyme-linked immunoassay. Age, race, sex, country of residence, general health
      status, age at time of measles immunization, and time from immunization to
      sampling were recorded. RESULTS: Of the 1052 children enrolled in the study, US
      children (n=719) had a significantly higher measles seroprevalence (87%) compared
      with Canadian children (n=333) (76%; P<.001). After adjustment for time from
      immunization and age at immunization, the differences in seropositive rates were
      no longer significant (odds ratio [OR], 1.53; 95% confidence interval, 0.87-2.69;
      P=.15). We found a significant dose-response relationship between age at the time
      of immunization and the odds of being seropositive after immunization, with ORs
      varying from 1 with immunization at 13 months or younger to 2.30 with
      immunization at 16 months of age (P=.01). CONCLUSIONS: The current US policy of
      immunizing with the first dose of measles at the age of 12 months may be less
      effective than a policy of immunizing at 12 to 15 months of age. These findings
      may be highly significant as we move toward an era in which measles exposure may
      be rare and policies are developed to eradicate measles.

PMID- 12004995
TI  - Secondary causes of osteoporosis.
AB  - Secondary causes of bone loss are not often considered in patients who are
      diagnosed as having osteoporosis. In some studies, 20% to 30% of postmenopausal
      women and more than 50% of men with osteoporosis have a secondary cause. There
      are numerous causes of secondary bone loss, including adverse effects of drug
      therapy, endocrine disorders, eating disorders, immobilization, marrow-related
      disorders, disorders of the gastrointestinal or biliary tract, renal disease, and
      cancer. Patients who have undergone organ transplantation are also at increased
      risk for osteoporosis. In many cases, the adverse effects of osteoporosis are
      reversible with appropriate intervention. Because of the many treatment options
      that are now available for patients with osteoporosis and the tremendous advances
      that have been made in understanding the pathogenesis and diagnosis of the
      condition, it is important that medical disorders are recognized and appropriate
      interventions are undertaken. This article provides the framework for
      understanding causes of bone loss and approaches to their management.

PMID- 12004996
TI  - Preconception care by the nonobstetrical provider.
AB  - Clinicians who provide health care to women during their childbearing years have
      the opportunity to affect pregnancy outcomes positively through preconception
      care. The goal of preconception care is to identify medical and social conditions
      that may put the mother or fetus at risk. Key elements include screening for
      certain infectious diseases, obtaining genetic history, updating immunizations,
      providing specific nutritional advice, and optimizing health status. Some women,
      and their partners, may require additional care, including a prepregnancy
      consultation with an obstetrician or maternal-fetal medicine specialist. The
      clinician can also offer advice that may enhance conception and encourage either
      early prenatal care when a pregnancy is achieved or early evaluation for
      infertility.

PMID- 12004997
TI  - 16-year-Old boy with gross hematuria.

PMID- 12004998
TI  - Assessing the clinical significance of single items relative to summated scores.
AB  - How many items are needed to measure an individual's quality of life (QOL)? This
      article describes the strengths and weaknesses of single items and summated
      scores (from multiple items) as QOL measures. We also address the use of single
      global measures vs multiple subindices as measures of QOL. The primary themes
      that recur throughout this article are the relationships between well-defined
      research objectives, the research setting, and the choice single item vs summated
      scores to measure QOL. The conceptual framework of the study, the conceptual fit
      with the measure, and the purpose of the assessment should all be considered when
      choosing a measure of QOL. No "gold standard" QOL measure can be recommended
      because no "one size fits all." Single items have the advantage of simplicity at
      the cost of detail. Multiple-item indices have the advantage of providing a
      complete profile of QOL component constructs at the cost of increased burden and
      of asking potentially irrelevant questions. The 2 types of indices are not
      mutually exclusive and can be used together in a single research study or in the
      clinical setting.

PMID- 12004999
TI  - Patient, clinician, and population perspectives on determining the clinical
      significance of quality-of-life scores.
AB  - Despite the success of screening and treatment of major cancers in the United
      States, cancer remains a chronic condition dominated by symptoms and treatment
      related adverse effects. Because of these often taxing symptoms and adverse
      effects, numerous studies have been conducted to document the effects of cancer
      diagnosis and treatment on the quality of life (QOL) of patients. But there has
      been limited investigation of the clinical significance of QOL scores. This
      article examines the clinical significance of QOL scores from 3 key perspectives:
      patients, clinicians, and the general population. The patient's perspective
      includes an evaluation of the size of difference in scores that individual
      patients can detect and regard as important. The clinician perspective relies on
      whether the clinician believes the patient's condition has stayed the same vs
      whether changes have occurred (decline or improvement). The population
      perspective represents a democratic process in which the input or votes of a
      community of people are used to determine if health state A is clinically
      significantly different from health state B. While many clinicians and
      researchers advocate for QOL to be defined from the patient's perspective, the
      reality is that QOL is often defined by clinicians in terms of observable events.
      Even when measures are used in which the patient identifies how his or her life
      has been affected, it is often the clinician who interprets the clinical
      importance of this information. The clinician's perspective has value in framing
      an experience within the context of what is usual for a group of individuals, and
      the population perspective provides inputs as to how society may use limited
      resources. However, we conclude that a more prominent role for the patient's QOL
      perspective is needed.

PMID- 12005000
TI  - Thymic hyperplasia presenting as anterior mediastinal mass in 2 patients with
      Graves disease.
AB  - Graves disease is an autoimmune thyroid condition characterized by the production
      of autoantibodies against the thyrotropin receptor. The autoantibodies mimic the
      effect of the hormone on thyroid cells, which stimulates autonomous production of
      thyroxine and triiodothyronine. It has been hypothesized that cross-reactivity of
      autoantibodies may result in Graves ophthalmopathy and dermopathy. A seldom
      recognized feature of Graves disease is thymic hyperplasia. We report 2 patients
      with Graves disease and incidentally discovered anterior mediastinal masses
      presumed to be thymic hyperplasia. In both cases, these masses regressed
      spontaneously after treatment of hyperthyroidism.

PMID- 12005001
TI  - Peripartum cardiomyopathy presenting as an acute myocardial infarction.

PMID- 12005002
TI  - The thyroid gland: a brief historical perspective.

PMID- 12005003
TI  - The diagnosis and management of hypothyroidism.

PMID- 12005004
TI  - Interpretation of laboratory thyroid function tests for the primary care
      physician.

PMID- 12005005
TI  - Pitfalls to avoid while interpreting thyroid function tests: five illustrative
      cases.

PMID- 12005006
TI  - Management of thyrotoxicosis.

PMID- 12005007
TI  - Euthyroid sick syndrome.

PMID- 12005008
TI  - Cost-effective management of thyroid nodules and nodular thyroid goiters.

PMID- 12005009
TI  - Medication update. Thyroid supplements. Antithyroid medications.

PMID- 12005010
TI  - Coverage of thyroid function studies.

PMID- 12005011
TI  - Awareness and use of over-the-counter pain medications: a survey of emergency
      department patients.
AB  - BACKGROUND: A survey study was done to determine basic knowledge about and use of
      over-the-counter (OTC) pain medications among patients seen in our emergency
      department (ED). The hypothesis was that knowledge about OTC pain medications
      would be correlated with demographic characteristics. METHODS: The study was a
      prospective 21-question survey during randomized 4-hour shifts over a 6-week
      study period. RESULTS: Of the 213 subjects who participated, 143 (67%) reported
      having used some form of nonsteroidal anti-inflammatory drug (NSAID), and 127
      (60%) had used acetaminophen products recently. Women were more aware of toxic
      interactions and gastrointestinal (GI) irritation related to these medications.
      Ibuprofen use correlated with age (younger individuals used more) and having no
      primary physician (those without a physician used less). Knowledge about GI
      effects correlated with age, sex, and education. Knowledge about renal and
      hepatic problems correlated with age and education. CONCLUSION: Many patients use
      OTC pain medications. Many are ill informed about their use and side effects.
      More education is needed.

PMID- 12005012
TI  - Heterotaxy syndrome with severe pulmonary hypertension in an adult.
AB  - Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs
      ambiguus, congenital heart defects, and splenic malformations. We report the case
      of an adult with heterotaxy syndrome (including situs ambiguus, bilateral
      superior vena cava, hypoplastic right-sided spleen and portosystemic shunts)
      presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory
      therapy was initiated, leading to marked reduction of clinical symptoms. This
      case exhibits 2 particular and partially novel features: primary diagnosis of
      heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may
      be associated with pulmonary hypertension, possibly on the basis of longstanding
      portosystemic shunts.

PMID- 12005013
TI  - Can elbow extension be used as a test of clinically significant injury?
AB  - BACKGROUND: The objective of this study was to evaluate whether a simple test of
      full elbow extension was a reliable indicator of bone/joint injury at the elbow
      joint. METHODS: In this prospective study, patients with acute elbow injuries
      were asked to fully extend the injured elbow. Radiologists blinded to the results
      of the extension test interpreted the radiographs. RESULTS: Of 114 patients with
      acute elbow injury entered into the study, 110 underwent adiographic evaluation.
      Inability to extend the elbow was found in 37 of 38 patients with bone injury.
      Only 1 of 54 patients who were able to fully extend the elbow was found to have
      bone/joint injury. The sensitivity and specificity of the elbow-extension test
      for identification of bone/joint injury was 97% and 69%, respectively.
      CONCLUSIONS: The elbow-extension test can be used as a sensitive clinical
      screening test for patients with acute elbow injuries.

PMID- 12005014
TI  - Rhabdomyolysis of infectious and noninfectious causes.
AB  - BACKGROUND: This study was done to determine variables associated with infectious
      rhabdomyolysis (IRM). METHODS: In this retrospective case-control study,
      rhabdomyolysis (RM) was defined as a fivefold or greater elevation in creatine
      kinase (CK) levels with a muscle/brain (MB) fraction <5%. Patients with
      myocardial infarction or cerebrovascular accident or a recent history of surgery,
      trauma, or immobilization were excluded. RESULTS: We analyzed 52 cases of RM seen
      at our institution between 1992 and 2000; IRM was the most frequent cause (31%),
      most commonly respiratory tract infections (38%). When a microorganism could be
      identified (50%), it was more often gram-negative (63%). Patients with IRM were
      elderly and had fever and lower CK levels. Infectious rhabdomyolysis was
      associated with a higher morbidity but not with a higher risk of death.
      CONCLUSIONS: Infectious rhabdomyolysis is the main cause of RM and must be
      suspected in elderly patients with fever and low levels of CK.

PMID- 12005015
TI  - Medical malpractice and respondeat superior.
AB  - The legal concept of vicarious liability and the Doctrine of Respondeat Superior
      occurs when the servant (employee) commits a tort or civil wrong within the scope
      of employment and the master (employer) is held liable although the master may
      have done nothing wrong. In this article, legal cases are presented to emphasize
      the importance of these issues, which frequently involve physician extenders and
      physicians as employers in our current health care climate. Physicians need to be
      aware of this doctrine in the supervision of their staff and their day-to-day
      medical practice.

PMID- 12005016
TI  - A rare form of hypothyroidism.
AB  - Secondary hypothyroidism is extremely rare. In the majority of cases, there is a
      genetic (gene mutations) or structural (mass effect or infiltration) basis for
      central hypothyroidism, and there is simultaneous deficiency of other
      adenohypophysial hormones. Isolated deficiency of thyrotropin is even rarer. This
      report features the case of a woman who had isolated thyrotropin deficiency, with
      the remainder of the anterior pituitary hormones being normal. The various causes
      of central hypothyroidism and the role of the thyrotropin-releasing hormone test
      are briefly described.

PMID- 12005017
TI  - Coma and thyroid storm in apathetic thyrotoxicosis.
AB  - We report the case of an 87-year-old woman with coma who was found to be in
      thyrotoxic crisis. The patient had a recent history of decreased mentation and
      apathy, and laboratory findings were found to be consistent with hyperthyroidism.
      After a stormy course, the clinical condition recovered to baseline, with return
      of laboratory values to normal following antithyroid therapy. We provide the
      details of this rarely documented presentation of apathetic hyperthyroidism with
      thyroid storm and coma and review the characteristics of similar cases in the
      literature.

PMID- 12005018
TI  - Spontaneous pneumothorax during pregnancy.
AB  - Spontaneous pneumothorax complicating pregnancy is rare. Only 41 cases have been
      previously published. We describe a case of spontaneous pneumothorax successfully
      treated with tube thoracostomy during the 38th week of pregnancy. Under epidural
      anesthesia, the patient had vaginal delivery of a healthy male infant 36 hours
      after tube thoracostomy.

PMID- 12005019
TI  - Proinflammatory and hematopoietic cytokines in reactive and clonal
      thrombycytosis.

PMID- 12005020
TI  - Diabetic foot: evaluation and management.

PMID- 12005021
TI  - Conditioned medium from MCF-7 cell line induces myofibroblast differentiation,
      decreased cell proliferation, and increased apoptosis in cultured normal
      fibroblasts but not in fibroblasts from malignant breast tissue.
AB  - We studied the effect of conditioned medium (CM) obtained from cultures of
      oestrogen-receptor positive breast cancer MCF7 cell line on the differentiation,
      proliferation and apoptosis patterns of cultured breast fibroblasts from normal
      interstitial and malignant stromal tissue. Fibroblasts were grown in the presence
      or absence of CM and examined for the differentiation pattern by
      immunofluorescence and Western blotting procedures, for proliferation profile by
      Ki67 expression, and for apoptosis by the terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labelling technique. Monoclonal antibodies specific for
      non-muscle (NM), smooth muscle (SM) lineage and differentiation markers were
      applied to these cultures. CM is able to induce a SM-like differentiation in
      interstitial fibroblasts, i.e., essentially myofibroblast formation. Fibroblasts
      from tumour stroma showed the presence of a small number of smooth muscle cells
      (SMC) along with a large number of myofibroblasts. Treatment of these cultures
      with CM was unable to change this pattern. Only normal fibroblasts were
      responsive to the proliferation/apoptotic-inhibitory effect of the CM. These data
      suggest that structural and functional differences exist between stromal
      fibroblasts from normal breast and breast cancer with respect to the
      responsiveness to soluble factors present in the CM. We hypothesize that the lack
      of in vitro sensitivity to CM shown by 'tumour' fibroblasts is the result of an
      in vivo inherent and stable phenotypic change on the fibroblasts surrounding
      breast tumour cells occurring via a paracrine mechanism.

PMID- 12005022
TI  - Peptidases play an important role in cataractogenesis: an immunohistochemical
      study on lenses derived from Shumiya cataract rats.
AB  - The role of proteolytic enzymes in Shumiya cataract rats in alterations to lens
      proteins during cataract formation was studied immunohistochemically using
      antibodies against exopeptidases, such as lysosomal dipeptidyl peptidase II (DPP
      II), cytosolic dipeptidyl peptidase III, and soluble and membrane-bound alanyl
      aminopeptidases, and against cytosolic endopeptidases such as mu- and m-calpains,
      and 20S proteasome. AlphaB-crystallin was detected as a proteolytic marker in the
      lenses. A constant immunoreactivity against all the antibodies employed was
      observed in the lens epithelium independent of the strain and age of the rats. A
      weak immunoreactivity against exo- and endopeptidases and an intense reactivity
      against alphaB-crystallin were observed in the lens fibres of control rats at all
      ages. The immunoreactivity of these peptidases in lens fibres increased with age
      in cataract rats, but that of alphaB-crystallin decreased. No reactivity against
      exo- and endopeptidases was seen in the perinuclear region of lenses of control
      rats at all ages or in Shumiya cataract rats at 8 and 10 weeks of age, but an
      intense reactivity against these peptidases was observed in the lens perinuclear
      region of lenses in cataract rats at 12 and 14 weeks of age. AlphaB-crystallin
      immunoreactivity was observed with ordered striations in the lens perinuclear
      region of all control rats whereas the striations in this area of cataract rat
      lens were disorganized. Membrane-bound alanyl aminopeptidase was detected feebly
      in the lens epithelium and fibres of both types of rat at all weeks of age. These
      findings indicate that exo- and endopeptidases, except for membrane-bound alanyl
      aminopeptidase, are expressed intensively and are age-dependent. Conversely, the
      amount of alphaB-crystallin decreased with age in lens fibres of cataract rats.
      Calpains (mu- and m-), 20S proteasome, dipeptidyl peptidases II and III and
      soluble alanyl aminopeptidase are thought to induce lens opacification
      kinetically during cataract formation in Shumiya cataract rats through the
      intracellular turnover of lens proteins.

PMID- 12005023
TI  - Nidogen-1 and nidogen-2 are found in basement membranes during human embryonic
      development.
AB  - The recently identified nidogen-2 is a matrix protein showing homology to the
      well-known basement membrane molecule nidogen-1. Nidogen-1 might well serve as a
      link between laminin-1 and collagen type IV and thus stabilise certain basement
      membranes in vivo and play a major role in embryogenesis. However, the exact
      tissue distribution of nidogen-1 and nidogen-2 during human embryogenesis is
      still unclear. As a first step towards the elucidation of their possible cell
      biological functions during human development, we compared the distribution of
      both nidogens during human organogenesis at the light microscope level. Nidogen-2
      and nidogen-1 were found to be ubiquitous components of basement membrane zones
      underneath developing epithelia of most of the major organ systems. However, in
      the developing intestine and the pancreas anlage, only nidogen-1 was present in
      the epithelial basement membrane zones of all developmental stages investigated.
      Our data suggest that nidogen-2 and nidogen-1, as is known for mouse development,
      could well participate in cell biological functions during human development.
      These two proteins might well be able to fulfil identical functions during human
      organogenesis.

PMID- 12005024
TI  - DNase I is present in the chief cells of human and rat stomachs.
AB  - The distribution of deoxyribonuclease I (DNase I) in human and rat stomachs was
      examined by biochemical, molecular biological and immunohistochemical techniques.
      By the use of monoclonal anti-human DNase I and polyclonal anti-rat DNase I
      antibodies, we determined that strong immunoreactivity was present in the
      cytoplasm of chief cells of the human fundus and the rat pars glandularis,
      respectively. High DNase I enzyme activity was detected in tissue homogenates of
      both human fundus and rat pars glandularis. The presence of DNase I-specific mRNA
      was verified by reverse transcriptase-polymerase chain reaction analysis of the
      total RNAs extracted from human and rat stomachs. Immunoelectron microscopy
      revealed gold particles localized in the chief cells, with most labelling in
      exocrine secretory granules. These results show that the chief cells of human and
      rat stomach produce DNase I. This is the first report to demonstrate that
      secretion of DNase I is controlled by the chief cells in human and rat stomachs.

PMID- 12005025
TI  - GABA immunoreactivity in the human cerebellar cortex: a light and electron
      microscopical study.
AB  - The distribution of gamma-aminobutyric acid (GABA) in surgical samples of human
      cerebellar cortex was studied by light and electron microscope
      immunocytochemistry using a polyclonal antibody generated in rabbit against GABA
      coupled to bovine serum albumin with glutaraldehyde. Observations by light
      microscopy revealed immunostained neuronal bodies and processes as well as axon
      terminals in all layers of the cerebellar cortex. Perikarya of stellate, basket
      and Golgi neurons showed evident GABA immunoreactivity. In contrast, perikarya of
      Purkinje neurons appeared to be negative or weakly positive. Immunoreactive
      tracts of longitudinally- or obliquely-sectioned neuronal processes and punctate
      elements, corresponding to axon terminals or cross-sectioned neuronal processes,
      showed a layer-specific pattern of distribution and were seen on the surface of
      neuronal bodies, in the neuropil and at microvessel walls. Electron microscope
      observations mainly focussed on the analysis of GABA-labelled axon terminals and
      of their relationships with neurons and microvessels. GABA-labelled terminals
      contained gold particles associated with pleomorphic vesicles and mitochondria
      and established symmetric synapses with neuronal bodies and dendrites in all
      cortex layers. GABA-labelled terminals associated with capillaries were seen to
      contact the perivascular glial processes, basal lamina and endothelial cells and
      to establish synapses with subendothelial unlabelled axons.

PMID- 12005026
TI  - Differential expression of dentin matrix protein 1, type I collagen and
      osteocalcin genes in rat developing mandibular bone.
AB  - The expression of dentin matrix protein 1 (Dmp1) mRNA has been compared with that
      of type I collagen and osteocalcin mRNAs during bone formation in the rat
      mandible, using in situ hybridization. At embryonic day 15 (E15), type I collagen
      and osteocalcin mRNAs were expressed by the majority of newly-differentiated
      osteoblasts attached to unmineralized bone matrices, whereas Dmp1 mRNA expression
      was confined to only a few osteoblasts. Expression of these genes increased as
      the number of osteoblasts increased in specimens from E16 to E18. At E20,
      expression of Dmp1, type I collagen and osteocalcin was also observed in
      osteocytes. Dmp1 expression continued in osteocytes as they matured up to the 90
      day-old specimens, whereas type I collagen and osteocalcin expression in
      osteocytes almost disappeared at 30 days of postnatal life. In contrast,
      osteoblasts continued to express type I collagen and osteocalcin in 90-day-old
      rats, but transiently expressed Dmp1 mRNA, which was seen in the minority of
      osteoblasts at 14 days of postnatal life. These data show that the developmental
      expression patterns of Dmp1 in osteogenic differentiation differ from those of
      type I collagen and osteocalcin, and Dmp1 appears to be expressed by osteocytes
      throughout ossification in the skeleton. These observations indicate that Dmp1
      may serve unique biological functions in osteocyte and bone metabolism.

PMID- 12005027
TI  - Hyaluronan digestion and synthesis in an experimental model of metastatic tumour.
AB  - To approach the question of hyaluronan catabolism in tumours, we have selected
      the cancer cell line H460M, a highly metastatic cell line in the nude mouse.
      H460M cells release hyaluronidase in culture media at a high rate of 57
      pU/cell/h, without producing hyaluronan. Hyaluronidase was measured in the H460M
      cell culture medium at the optimum pH 3.8, and was not found above pH 4.5, with
      the enzyme-linked sorbent assay technique and zymography. Tritiated hyaluronan
      was digested at pH 3.8 by cells or cell membranes as shown by gel permeation
      chromatography, but no activity was recorded at pH 7 with this technique.
      Hyaluronan was digested in culture medium by tumour slices, prepared from tumours
      developed in nude mice grafted with H460M cells, showing that hyaluronan could be
      digested in complex tissue at physiological pH. Culture of tumour slices with
      tritiated acetate resulted in the accumulation within 2 days of radioactive
      macromolecules in the culture medium. The radioactive macromolecular material was
      mostly digested by Streptomyces hyaluronidase, showing that hyaluronan was its
      main component and that hyaluronan synthesis occurred together with its
      digestion. These results demonstrate that the membrane-associated hyaluronidase
      of H460M cells can act in vivo, and that hyaluronan, which is synthesised by the
      tumour stroma, can be made soluble and reduced to a smaller size by tumour cells
      before being internalised and further digested.

PMID- 12005028
TI  - Intracellular localization of serotonin in mast cells of the colon in normal and
      colitis rats.
AB  - Intracellular localization of serotonin (5-HT) in the mast cells of two
      phenotypes in normal rat colon and dextran sodium sulphate-induced colitis was
      studied by immunoelectron microscopy with a quantitative analysis of the
      distribution of immunogold labelling. Mucosal mast cells in normal rats contained
      round shape secretory granules with varying electron density. Immunogold
      labelling for 5-HT was concentrated over the secretory granules. In mucosal mast
      cells from colitis rats, vacuolated granules without 5-HT labelling were
      frequently observed and immunogold labelling over the secretory granules was
      significantly increased compared to controls. On the other hand, connective
      tissue mast cells in normal rats contained oval shape secretory granules with
      homogeneous electron density. Their immunogold labelling was diffusely scattered
      over the secretory granules as well as over the cytoplasm. In connective tissue
      mast cells from colitis rats, secretory granules with high electron density were
      increased and the immunogold labelling over the secretory granules was much
      higher than that in controls. The present results suggest that intracellular
      localization of 5-HT is different in two phenotypes of mast cells and they may
      release 5-HT in a different manner. Mucosal mast cells may release 5-HT by a
      degranulation or exocytosis, while connective tissue mast cells may release 5-HT
      by a diacrine manner of secretion.

PMID- 12005029
TI  - The hypothalamo-hypophyseal system of the white seabream Diplodus sargus:
      immunocytochemical identification of arginine-vasotocin, isotocin, melanin
      concentrating hormone and corticotropin-releasing factor.
AB  - The distribution of the neurosecretory hormones vasotocin, isotocin and melanin
      concentrating hormone and the hypophysiotropic hormone corticotropin-releasing
      factor was studied in the hypothalamo-hypophyseal system of the white seabream
      (Diplodus sargus) using immunocytochemical techniques. Magnocellular and
      parvocellular perikarya immunoreactive for arginine-vasotocin and isotocin were
      present in the nucleus preopticus. Perikarya immunoreactive for arginine
      vasotocin extended more caudally with respect to isotocin-immunoreactive
      perikarya. Parvocellular perikarya were located at rostroventral levels and
      magnocellular perikarya in the dorsocaudal portion of the nucleus. Arginine
      vasotocin and isotocin did not coexist in the same neuron. Fibres immunoreactive
      for arginine-vasotocin and isotocin innervated all areas of neurohypophysis and
      terminate close to corticotropic and melanotropic cells. Perikarya immunoreactive
      for melanin-concentrating hormone and corticotropin-releasing factor were
      observed in the nucleus lateralis tuberis, with a few neurons in the nucleus
      periventricularis posterior. In addition, melanin-concentrating hormone
      immunoreactive perikarya were detected in the nucleus recessus lateralis. The
      preoptic nucleus did not show immunoreactivity for these antisera. Fibres showing
      melanin-concentrating hormone and corticotropin-releasing factor immunoreactivity
      ended close to the melanotropic and somatolactotrophic cells of the pars
      intermedia, and close to the corticotrophic cells of the rostral pars distalis.

PMID- 12005030
TI  - Immunogold confirmation that utrophin is localized to the normal position of
      dystrophin in dystrophin-negative transgenic mouse muscle.
AB  - It has been shown previously that when utrophin is highly expressed in mice which
      lack dystrophin, the muscle pathology is prevented. Immunohistochemical evidence
      strongly suggests that utrophin in these transgenic mice occupies the position
      normally filled by dystrophin, although it is not possible to establish this
      firmly at the level of the light microscope. Using the higher resolution provided
      by the electron microscope, we demonstrate here by immunogold labelling with both
      monoclonal and polyclonal antibodies that utrophin, in both its truncated and
      full-length forms, is indeed specifically located in the subcellular position
      usually occupied by dystrophin in normal muscle. Moreover, when double-labelling
      of utrophin and beta-dystroglycan was carried out, colocalisation of the two
      labels was often seen, indicating an association of the two proteins.
      Furthermore, when both utrophin and dystrophin were labelled in a transgenic line
      in which both were simultaneously expressed, the sites of both proteins were in
      the same zone in relation to the plasma membrane. When both proteins were
      present, the density of labelling of each was reduced compared with when they are
      expressed individually, suggesting that there is a finite number of binding
      sites. These results constitute further support for the view that utrophin might
      be therapeutically substituted for dystrophin in dystrophic muscle.

PMID- 12005031
TI  - Ontogenesis of oxidative reaction of 17beta-hydroxysteroid dehydrogenase and
      11beta-hydroxysteroid dehydrogenase in rat Leydig cells, a histochemical study.
AB  - The enzyme 17beta-hydroxysteroid dehydrogenase is required for the synthesis and
      11beta-hydroxysteroid dehydrogenase for the regulation of androgens in rat Leydig
      cells. This histochemical study describes ontogenetic changes in distribution and
      intensity of these enzymes in Leydig cells from postnatal day (pnd) 1-90. Using
      NAD or NADP as the cofactor, 17beta-hydroxysteroid dehydrogenase (substrate: 5
      androstene-3beta,17beta-diol) peaks were observed on pnd 16 for fetal Leydig
      cells and on pnd 19 and 37 for adult Leydig cells. Between pnd 13 and 25 the
      fetal cells showed a higher intensity for the 17beta-enzyme than the adult cells;
      more fetal Leydig cells were stained with NADP, whereas more adult cells were
      positive with NAD on pnd 13 and 16. A nearly identical distribution of 11beta
      hydroxysteroid dehydrogenase (substrate: corticosterone) was observed with NAD or
      NADP as the cofactor; the reaction was present from pnd 31 onwards, first in a
      few adult Leydig cells and later in almost all these cells homogeneously. The
      ontogenetic curves of the two enzymes show an inverse relationship. To conclude:
      (1) Generally, a stronger reaction for 17beta-hydroxysteroid dehydrogenase is
      shown with NAD as cofactor than with NADP; using NADP, fetal Leydig cells show a
      stronger staining than adult Leydig cells. (2) The data possibly support the
      notion of a new isoform of 11beta-hydroxysteroid dehydrogenase in addition to
      types 1 and 2.

PMID- 12005032
TI  - Comparison of two methods for radioiodination on the oxidizability properties of
      low density lipoprotein.
AB  - Radiolabeling of low density lipoprotein (LDL) apoB100 with 125I, an oxidative
      process, is commonly used in lipoprotein investigation. Since 1) LDL is unstable
      and oxidation-prone, 2) the modification of apoB100 by oxidation increases the
      negative charge of particles and leads to the uptake of modified LDL through the
      scavenger receptor pathway, and 3) oxidized LDL is cytotoxic, it is relevant to
      investigate whether the oxidative stability of LDL is influenced by its labeling
      with 125I. The aim of this study was to investigate and compare lipid and protein
      oxidation markers in human LDL after labeling with 125I by two widely adopted
      methods that use ICl or the chloramide 1,3,4,6-tetrachloro-3alpha,6alpha
      diphenylglycoluril as the oxidizing agent. Native LDL served as a common control
      and sham-iodinated LDL as a handling control for each procedure. The resistance
      against copper-induced oxidation of 125I-LDL labeled with ICl was similar to that
      of controls with regard to the lag time and maximal amount of conjugated diene
      formed, as there were levels of initial conjugated diene, alpha-tocopherol, and
      tryptophan. However, radioiodination with the chloramide accelerated the onset of
      the rapid phase of LDL oxidation due to a drastic depletion of alpha-tocopherol
      and increased conjugated diene content. Measurements of copper-induced LDL
      oxidizability showed enhanced indices of lipid oxidation. The lag time and the
      time to maximal diene production were 65% and 30% shorter than controls. This was
      accompanied by a 50% reduced tryptophan fluorescence. The anionic surface charge
      of the LDL particle increased moderately with both labeling procedures. The
      results indicate that labeling of LDL with 125I may oxidize lipids and apoB100 to
      a variable extent, depending on the nature of the iodinating agent. This is why
      assessment of the oxidizability properties of 125I-labeled LDL is recommended for
      reliable biological studies.

PMID- 12005033
TI  - Increased blood ammonia in hypoxia during exercise in humans.
AB  - The effect of acute hypoxia on blood concentration of ammonia ([NH3]b) and
      lactate (la-]b) was studied during incremental exercise(IE), and two-step
      constant workload exercises (CE). Fourteen endurance-trained subjects performed
      incremental exercise on a cycle ergometer under normoxic (21% O2) and hypoxic
      (10.4% O2) conditions. Eight endurance-trained subjects performed two-step
      constant workload exercise at sea level and at a simulated altitude of 5000 m
      (hypobaric chamber, P(B)=405 Torr; P(O2)=85 Torr) in random order. In normoxia,
      the first step lasted 25 minutes at an intensity of 85 % of the individual
      ventilatory anaerobic threshold (AT(vent), ind) at sea level. This reduced
      workload was followed by a second step of 5 minutes at 115% of their AT(vent),
      ind. This test was repeated into a hypobaric chamber, at a simulated altitude of
      5,000 m. The first step in hypoxia was at an intensity of 65 % of AT(vent), ind.,
      whereas workload for the second step at simulated altitude was the same as that
      of the first workload in normoxia (85 % of AT(vent), ind). During IE, [NH3]b and
      [la-]b were significantly higher in hypoxia than in normoxia. Increases in these
      metabolites were highly correlated in each condition. The onset of [NH3]b and [la
      ]b accumulation occurred at different exercise intensity in normoxia (181W for
      lactate and 222W for ammonia) and hypoxia (100W for lactate and 140W for
      ammonia). In both conditions, during CE, [NH3]b showed a significant increase
      during each of the two steps, whereas [la-]b increased to a steady-state in the
      initial step, followed by a sharp increase above 4 mM x L(-1) during the second.
      Although exercise intensity was much lower in hypoxia than in normoxia, [NH3]b
      was always higher at simulated altitude. Thus, for the same workload, [NH3]b in
      hypoxia was significantly higher (p<0.05) than in normoxia. Our data suggest that
      there is a close relationship between [NH3]b and [la-]b in normoxia and hypoxia
      during graded intensity exercises. The accumulation of ammonia in blood is
      independent of that of lactate during constant intense exercise. Hypoxia
      increases the concentration of ammonia in blood during exercise.

PMID- 12005034
TI  - Influence of fitness on the integrated neuroendocrine response to aerobic
      exercise until exhaustion.
AB  - A group of trained and sedentary men performed an incremental graded exercise
      test to exhaustion in order to assess the organic response of the two main stress
      activated systems: the sympathetic nervous system with its endocrine component
      (the adrenal medulla), and the hypothalamic-pituitary-adrenal (HPA) axis. Maximal
      plasma concentrations of ACTH, cortisol and endogenous opioids (beta-endorphins)
      were obtained at the end of the exercise-test in the trained group. Thus ACTH
      increased from basal value of 21.25 +/- 2.5 pg/ml to 88.78 +/- 11.8 pg/ml at the
      end of the exercise (p<0.01); cortisol, from 16.56 microg/dl +/- 4.94 microg/dl
      to 23.80 +/- 4.57 microg/dl in min 15 of the recovery period (p<0.001); and beta
      endorphin from 21.80 +/- 8.33 pmol/ml to 64.36 +/- 9.8 pmol/ml in min 3 of the
      recovery period (p<0.05). Catecholamine levels were increased from initial values
      at the end of the effort test in both control and trained groups. Control
      subjects exhibited a higher responsiveness compared to trained and showed
      superior intrinsic stimulation of the sympathetic nervous system. These results
      reveal a different response according to fitness in a physical stress situation.

PMID- 12005035
TI  - Influence of dietary protein type and iron source on the absorption of amino
      acids and minerals.
AB  - The apparent digestibility coefficient (ADC) of amino acids and the balance of
      minerals (calcium, phosphorus, magnesium and iron) has been determined in rats
      fed four diets differing in the protein type (casein or soy protein) and iron
      source (ferrous sulphate or lactate) in order to study the possible interactions
      of these nutrients. The availability of amino acids, especially essential amino
      acids, was greater in the diet made with animal protein (casein). The iron source
      also affected the absorption of most amino acids in all the diets assayed with
      ferrous sulphate being greater. The balance of iron, magnesium and phosphorus was
      higher in the diets containing animal protein. The retention of calcium and
      magnesium was significantly greater when ferrous sulphate was used as iron
      source. These results demonstrate the important interaction between amino acids
      and minerals and between the minerals themselves, which must be carefully studied
      when selecting different types of protein or mineral sources in human or animal
      nutrition.

PMID- 12005036
TI  - Participation of mitochondria in calcium signalling in the exocrine pancreas.
AB  - This minireview is an attempt to put together some of the recent advances
      regarding the implications of mitochondria in Ca2+ homeostasis. Although the main
      role of this cytoplasmic organelle is ATP supply to the cell, during the past
      years strong evidence has been accumulated supporting an active role of these
      organelles in Ca2+ handling by the cell. The discovery of mitochondrial specific
      fluorescent dyes has permitted the study of these organelles within living cells.
      Due to its ubiquitous localisation within the cytosol, mitochondria would play an
      important role in the modulation of the subcellular patterns of Ca2+ signalling,
      and therefore would act as modulators of Ca2+-dependent cellular processes.

PMID- 12005037
TI  - Verapamil sensitisation to alkaloids on colchicine-selected human colon
      adenocarcinoma cells.

PMID- 12005038
TI  - Leptin effect on galactose absorption in mice jejunum.

PMID- 12005039
TI  - Modification of RXRalpha expression according to the duration of a cafeteria
      diet.

PMID- 12005040
TI  - Cloning, sequencing, and expression of a gene encoding the monomeric isocitrate
      dehydrogenase of the nitrogen-fixing bacterium, Azotobacter vinelandii.
AB  - Isocitrate dehydrogenase (IDH: EC 1.1.1.42) of Azotobacter vinelandii was
      purified to an electrophoretically homogeneous state, and a gene (icd) encoding
      this enzyme was cloned and sequenced. The N-terminal amino acid sequence of the
      purified enzyme was consistent with that deduced from the nucleotide sequence of
      the icd gene. The deduced amino acid sequence of this gene showed high identity
      (62-66%) to those of the other bacterial monomeric IDHs. Expression of the icd
      gene in Escherichia coli was examined by measuring the enzyme activity and mRNA
      level. Primer extension analyses revealed that two species of mRNAs with
      different lengths of 5'-untranslated regions (TS-1 and TS-2) were present, of
      which the 5'-terminals (TS-1 and TS-2 sites) were cytosines located at 244 bp and
      101 bp upstream of translational initiation codon, respectively. Conserved
      promoter elements were present at -35 and -10 regions from the TS-1 site, whereas
      no such a common motif was found in the upstream region of the TS-2 site.
      Deletion of the promoter elements upstream of the TS-1 site resulted in complete
      loss of IDH activity in the E. coli transformant. When the promoter elements
      upstream of the TS-1 site were intact, the levels of TS-1 and TS-2 were varied
      greatly by altering exogenous nutrients for growth. The cells grown in a nutrient
      rich medium produced large amounts of TS-1 and had a low level of IDH activity.
      In a nutrient-poor medium, the cells contained large amounts of TS-2 and high
      levels of IDH activity.

PMID- 12005041
TI  - Inhibition of lymphocyte kinase Lck and phosphatidylinositol 3-kinase by a novel
      immunosuppressant, lymphostin.
AB  - Lck is a Src-family tyrosine kinase that is expressed predominantly in T cells,
      where it plays important roles in T-cell activation. Lymphostin was isolated from
      Streptomyces sp. as an inhibitor of Lck. As previously reported, lymphostin
      inhibited Lck (IC50 0.05 microM) and the mixed lymphocyte reaction (IC50 0.009
      microM). We have now examined the mechanism of inhibition by lymphostin.
      Lymphostin inhibited protein-tyrosine kinase activity in Jurkat T cells,
      demonstrating the effectiveness of the compound at the cellular level.
      Furthermore, lymphostin suppressed delayed-type hypersensitivity in mice.
      However, the inhibitory activity against Lck at the cellular level was weaker
      than that against the mixed lymphocyte reaction. Thus, we examined the effects of
      lymphostin on other kinases. Interestingly, lymphostin also inhibited
      phosphatidylinositol 3-kinase (IC50 0.001 microM). Consequently, we conclude that
      lymphostin inhibits the mixed lymphocyte reaction and delayed-type
      hypersensitivity not only through the blockade of Lck, but through the blockade
      of phosphatidylinositol 3-kinase as well.

PMID- 12005042
TI  - Purification and characterization of an endo-1,4-beta-glucanase from Neisseria
      sicca SB that hydrolyzes beta-1,4 linkages in cellulose acetate.
AB  - An enzyme catalyzing hydrolysis of beta-1,4 bonds in cellulose acetate was
      purified 18.3-fold to electrophoretic homogeneity from a culture supernatant of
      Neisseria sicca SB, which can assimilate cellulose acetate as the sole carbon and
      energy source. The molecular mass of the enzyme was 41 kDa and the isoelectric
      point was 4.8. The pH and temperature optima of the enzyme were 6.0-7.0 and 60
      degrees C. The enzyme catalyzed hydrolysis of water-soluble cellulose acetate
      (degree of substitution, 0.88) and carboxymethyl cellulose. The Km and Vmax for
      water-soluble cellulose acetate and carboxymethyl cellulose were 0.242% and 2.24
      micromol/min/mg, and 2.28% and 12.8 micromol/min/mg, respectively. It is
      estimated that the enzyme is a kind of endo-1,4-beta-glucanase (EC 3.2.1.4) from
      the substrate specificity and hydrolysis products of cellooligosaccharides. The
      enzyme and cellulose acetate esterase from Neisseria sicca SB degraded water
      insoluble cellulose acetate by synergistic action.

PMID- 12005043
TI  - Active form of dipteran-specific insecticidal protein cryllA produced by Bacillus
      thuringiensis subsp. israelensis.
AB  - The nucleotide sequence of the cry11A gene from Bacillus thuringiensis subsp.
      israelensis strain HD522 was analyzed and the molecular characterization of
      CryllA toxin was done. The 70-kDa CryllA protoxin was processed in vitro into 36-
      and 32-kDa fragments by trypsin and into 34- and 32-kDa fragments by gut
      proteases from C. pipiens. These two processed fragments are associated together
      to form the heterodimer. The results of the binding assay with BBMV and the
      bioassay toward C. pipiens larvae suggested that the heterodimer was biologically
      as active as the non-digested CryllA toxin and the intramolecular cleavage did
      not promote the insecticidal activity. These results suggested that a probable
      complex of the 36- or 34-kDa and 32-kDa fragments was also one of the possible
      active forms of Cry11A, and that the biological functions of CryllA was not
      essentially affected by the intramolecular cleavage of the 70-kDa protein.

PMID- 12005044
TI  - A novel synthesis of branched high-molecular-weight (C40+) long-chain alkanes.
AB  - Many biological and geochemical questions remain concerning the structures,
      functions, and properties of naturally occurring high-molecular-weight (C40+)
      alkanes with various mid-chain alkylation patterns. Above C40, these alkanes are
      exceedingly difficult to separate and purify, and syntheses can be blocked by the
      low solubility of intermediates. To overcome these problems, a facile three-step
      synthesis employing the alkylation of 1,3-dithiane with a suitable alpha,omega
      dibromoalkane was developed. Bisalkylation of the bis(dithianyl)alkane
      intermediate with the appropriate 1-bromoalkane and subsequent desulfurization
      with Raney nickel furnished the desired long-chain alkane. Long-chain alkanes
      modified at mid-chain and/or symmetrically near the chain termini (or unmodified,
      i.e., long-chain n-paraffins) are accessible by the selection of appropriate
      bromoalkanes. Nine mid-chain methylated (C38H78 to C53H108), one symmetrical
      terminal-chain dimethylated (C40H82), and four linear (C44H90 to C58H118) long
      chain alkanes were synthesized by using this approach. High-temperature gas
      chromatography (HTGC) was found to have important advantages for evaluating the
      purity of the synthetic high-molecular-weight alkanes.

PMID- 12005045
TI  - Studies on the antimicrobial mechanisms of capsaicin using yeast DNA microarray.
AB  - Capsaicin is a pungent element in a variety of red peppers that are widely used
      as food additives and considered to be an antimicrobial factor. For our tests, we
      used yeast DNA micro-array methods to understand the mechanisms of inhibitory
      effects of capsaicin. The capsaicin treatment significantly induced 39 genes from
      approximately 6,000 genes. These induced genes were classified as multi-drug
      resistance transporter genes, membrane biosynthesis genes, genes encoding stress
      proteins, and uncharacterized genes. The growth abilities of the strains with the
      deletion of the induced genes suggest that capsaicin is pumped out of the yeast
      cells by the PDR5 transporter.

PMID- 12005046
TI  - Polyoxygenated cyclohexenes from the Chinese tree, Uvaria purpurea.
AB  - Four new polyoxygenated cyclohexenes, 2-O-acetyl-6-O-methylzeylenol (2), 2-O
      benzoyl-3-O-debenzoylzeylenone (5), 3-O-debenzoylzeylenone (6) and 3-O
      debenzoylgrandiflorone (8), were isolated from the leaves of Uvaria purpurea. 2-O
      acetyl-6-O-benzoylzeylenol (3) was also isolated for the first time as a natural
      product. Compounds 5-7 each showed inhibitory activity against the root growth of
      Lactuca sativa. Their structures were established by spectroscopic and chemical
      methods.

PMID- 12005047
TI  - Purification and characterization of pyridoxal 4-dehydrogenase from
      Aureobacterium luteolum.
AB  - A pyridoxal dehydrogenase was purified to homogeneity from Aureobacterium
      luteolum, which can use pyridoxine as a carbon and nitrogen source, and
      characterized. The enzyme was a dimeric protein with a subunit molecular weight
      of 38,000. It had several properties distinct from those of the partially
      purified enzyme from Pseudomonas MA-1. The optimum pH (8.0-8.5) was 0.8-1.3 lower
      than that of the Pseudomonas enzyme. The Aureobacterium enzyme showed much higher
      and lower affinities for NAD+ (Km, 0.140 +/- 0.008 mM) and pyridoxal (0.473 +/-
      0.109 mM), respectively, than those of the Pseudomonas enzyme. The Aureobacterium
      enzyme could use NADP+ as a substrate: the reactivity was 6.5% of NAD+. The
      enzyme was much more tolerant to metal-chelating agents. Irreversibility of the
      enzymatic reaction was shared by the two enzymes. No aldehyde dehydrogenase
      showed similarity to the amino-terminal amino acid sequence of the enzyme.

PMID- 12005048
TI  - Cysteine synthase of an extremely thermophilic bacterium, Thermus thermophilus
      HB8.
AB  - O-Acetyl-L-serine sulfhydrylase (EC 4.2.99.8) was first purified from an
      extremely thermophilic bacterium, Thermus thermophilus HB8, in order to ascertain
      that it is responsible for the cysteine synthesis in this organism cultured with
      either sulfate or methionine given as a sole sulfur source. Polyacrylamide gel
      electrophoreses both with and without SDS found high purity of the enzyme
      preparations finally obtained, through ammonium sulfate fractionation, ion
      exchange chromatography, gel filtration, and hydrophobic chromatography (or
      affinity chromatography). The enzyme activity formed only one elution curve in
      each of the four different chromatographies, strongly suggesting the presence of
      only one enzyme species in this organism. Molecular masses of 34,000 and 68,000
      were estimated for dissociated subunit and the native enzyme, respectively,
      suggesting a homodimeric structure. The enzyme was stable at 70 degrees C at pH
      7.8 for 60 min, and more than 90% of the activity was retained after incubation
      of its solution at 80 degrees C with 10 mm dithiothreitol. The enzyme was also
      quite stable at pH 8-12 (50 degrees C, 30 min). It had an apparent Km of 4.8 mM
      for O-acetyl-L-serine (with 1 mM sulfide) and a Vmax of 435 micromol/min/mg of
      protein. The apparent Km for sulfide was approximately 50 microM (with 20 mM
      acetylserine), suggesting that the enzyme can react with sulfide liberated very
      slowly from methionine. The absorption spectrum of the holo-enzyme and inhibition
      of the activity by carbonyl reagents suggested the presence of pyridoxal 5'
      phosphate as a cofactor. The apo-enzyme showed an apparent Km of 29 microM for
      the cofactor at pH 8. Monoiodoacetic acid (1 mM) almost completely inactivated
      the enzyme. The meaning of a very high enzyme content in the cell is discussed.

PMID- 12005049
TI  - Cloning and expression of Bombyx mori silk gland elongation factor 1gamma in
      Escherichia coli.
AB  - Elongation factor 1 (EF-1) from the silk gland of Bombyx mori consists of alpha-,
      beta-, gamma-, and delta-subunits. EF-1alpha GTP catalyzes the binding of
      aminoacyl-tRNA to ribosomes concomitant with the hydrolysis of GTP. EF
      1betagammadelta catalyzes the exchange of EF-1alpha-bound GDP for exogenous GTP
      and stimulates the EF-1alpha-dependent binding of aminoacyl-tRNA to ribosomes. EF
      1gamma cDNA, which contains an open reading frame (ORF) encoding a polypeptide of
      423 amino acid residues, was amplified and cloned by PCR from a silk gland cDNA
      library. The calculated molecular mass and predicted pI of the product were
      48,388 Da and 5.84, respectively. The silk gland EF-1gamma shares 67.3% amino
      acid identity with Artemia salina EF-lgamma. The N-terminal domain (amino acid
      residues 1-211) of silk gland EF-lgamma is 29.3% identical to maize glutathione S
      transferase. We demonstrated that silk gland EF-lgamma bound to glutathione
      Sepharose, suggesting that the N-terminal domain of EF-1gamma may have the
      capacity to bind to glutathione.

PMID- 12005050
TI  - Biosynthesis of rice phytoalexin: enzymatic conversion of 3beta-hydroxy-9beta
      pimara-7,15-dien-19,6beta-olide to momilactone A.
AB  - Momilactone A, a major rice diterpene phytoalexin, could be synthesized by
      dehydrogenation at the 3-position of 3beta-hydroxy-9beta-pimara-7,15-dien
      19,6beta-olide in rice leaves. The presence of 3beta-hydroxy-9beta-pimara-7,15
      dien-19,6beta-olide in UV-irradiated rice leaves was confirmed by comparing the
      mass spectra and retention times after a GC/MS analysis of the natural and
      synthetic compounds. The soluble protein fraction from UV-irradiated rice leaves
      showed dehydrogenase activity to convert 3beta-hydroxy-9beta-pimara-7,15-dien
      19,6beta-olide into momilactone A. The enzyme required NAD+ or NADP+ as a
      hydrogen acceptor. The optimum pH for the reaction was 8. The Km value to 3beta
      hydroxy-9beta-pimara-7,15-dien-19,6beta-olide was 36 microM when NAD+ was
      supplied as a cofactor at a concentration of 1 mM. 3fl-Hydroxy-9beta-pimara-7,15
      dien-19,6beta-olide and its dehydrogenase activity were induced in a time
      dependent manner by UV irradiation.

PMID- 12005051
TI  - Erinacine Q, a new erinacine from Hericium erinaceum, and its biosynthetic route
      to erinacine C in the basidiomycete.
AB  - Erinacines as cyathane-xylosides are known to have potent stimulating activity
      for nerve-growth-factor synthesis. Our search for new cyathane metabolites from a
      liquid culture of Hericium erinaceum YB4-6237 resulted in the isolation of a new
      erinacine named erinacine Q (1). NMR spectrometry and a chemical derivation from
      erinacine P (2) determined the compound to be a derivative in which the formyl
      group of erinacine P had been reduced to the hydroxymethyl group. To clarify the
      biosynthetic relationship between erinacine Q and the others, [1'-13C]erinacine Q
      ([1'-13C]-1) was chemically derived from [1'-13C]erinacine P ([1'-13C]-2) which
      had been prepared by feeding [1-13C]-D-glucose to the basidiomycete. The
      biotransformation of labeled erinacine Q into [1'-13C]erinacine C ([1'-13C]-5)
      via [1'-13C]erinacine P in this basidiomycete was demonstrated by NMR
      spectrometry.

PMID- 12005052
TI  - Purification and characterization of malate synthase from the glucose-grown wood
      rotting basidiomycete Fomitopsis palustris.
AB  - Malate synthase (EC 4.1.3.2), the key enzyme of the glyoxylate cycle, was
      purified to a homogeneous protein from the wood-rotting basidiomycete Fomitopsis
      palustris grown on glucose. The purified enzyme, with a molecular mass of 520
      kDa, was found to consist of eight 65-kDa subunits, and to have Km of 45 and 2.2
      microM for glyoxylate and acetyl-CoA, respectively. The enzyme activity was
      competitively inhibited by oxalate (K1, 8.5 microM) and glycolate (Ki, 17
      microM), and uncompetitively by coenzyme A (Ki, 100 microM). The potent
      inhibition of the activity by p-chloromercuribenzoate suggests that the enzyme
      has a sulfhydryl group at the active center. However, the enzyme was inhibited
      moderately by adenine nucleotides and weakly by some of the metabolic
      intermediates of glycolysis and tricarboxylic acid cycle. The enzyme was
      completely inactive in the absence of metal ions and was maximally activated by
      Mg2+ (Km, 0.4 microM), which also served to significantly prevent enzyme
      inactivation during storage.

PMID- 12005053
TI  - Syntheses of racemic and diastereomeric mixtures of 3,7,11,15
      tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane, the cuticular
      tetramethylalkanes of the tsetse fly, Glossina brevipalpis.
AB  - Cuticular hydrocarbons of the tsetse fly, Glossina brevipalpis, contain 3,7,11,15
      tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane as possible
      candidates for its contact sex pheromone. These were synthesized as racemic and
      diastereomeric mixtures starting from racemic citronellol and employing phenyl
      sulfone-mediated chain-elongation as the key reaction.

PMID- 12005054
TI  - Purification and characterization of two alpha-keto ester reductases from
      Streptomyces thermocyaneoviolaceus IFO 14271.
AB  - Two NADPH-dependent alpha-keto ester reductases (Streptomyces
      thermocyaneoviolaceus keto ester reductase, STKER-II and -III) were purified from
      S. thermocyaneoviolaceus IFO 14271, one of thermophilic actinomycetes. The
      molecular masses of native STKER-II and -III were estimated to be 60 kDa and 70
      kDa by gel filtration chromatography, respectively. These enzymes were both
      homodimers, with 29-kDa and 30-kDa subunit molecular masses based on SDS
      polyacrylamide gel electrophoresis. STKER-II and -III were stable from pH 7.0 to
      10.0 and pH 5.5 to 9.0, respectively. Ethyl 3-methyl-2-oxobutanoate was reduced
      by both enzymes isolated to the corresponding (R)-hydroxy ester with excellent
      enantiomeric excess. STKER-III showed high stereoselectivity for the reduction of
      bulky substrates, while the selectivity of the STKER-II-catalyzed reduction was
      low except for ethyl 3-methyl-2-hydrox-ybutanoate. Both enzymes had small Km
      values toward aliphatic keto esters having a long alkyl chain.

PMID- 12005055
TI  - Cloning and expression in Escherichia coli of a gene, hup, encoding the histone
      like protein HU of Bifidobacterium longum.
AB  - A genomic DNA library of Bifidobacterium longum ATCC15707 was transfected into an
      Escherichia coli strain deficient in both HU and IHF, the growth of which is cold
      sensitive because of the deficiency in these proteins. Cold-resistant colonies
      were selected and the DNA was cloned and sequenced. A polypeptide consisted of 93
      amino acids, a predicted molecular mass of 9983 Da with an isoelectric point of
      10.35, was deduced from an orf in the middle of the DNA fragment. The amino acid
      sequence was highly similar to HU family proteins, and 26 aas of N terminal was
      identical to a histone-like protein, HBI, a HU family protein of B. longum.
      Incapabilities of Mu phage propagation in an E. coli mutant deficient in HU or
      IHF could be suppressed by DNA bearing this orf. These results showed that the
      orf is a gene hup encoding HBI, a histone-like protein HU of B. longum.

PMID- 12005056
TI  - Rhamnose-binding lectins from steelhead trout (Oncorhynchus mykiss) eggs
      recognize bacterial lipopolysaccharides and lipoteichoic acid.
AB  - The interaction between bacteria and three L-rham-nose-binding lectins, named
      STL1, STL2, and STL3, from steelhead trout (Oncorhynchus mykiss) eggs was
      investigated. Although STLs bound to most Gram-negative and Gram-positive
      bacteria, they agglutinated only Escherichia coli K-12 and Bacillus subtilis
      among the bacteria tested. The binding was inhibited by L-rhamnose. STLs bound to
      distinct serotypes of lipopolysaccharides (LPSs), and showed much higher binding
      activities to smooth-type LPSs of Escherichia coli K-12 and Shigella flexneri 1A
      than to their corresponding rough-type LPSs. STLs also bound to lipoteichoic acid
      (LTA) of Bacillus subtilis. These results indicate that STLs bound to bacteria by
      recognizing LPSs or LTA on the cell surfaces.

PMID- 12005057
TI  - Identification and expression of a rat fatty acid elongase involved in the
      biosynthesis of C18 fatty acids.
AB  - A major part of the palmitic acid (C16:0) generated by fatty acid synthase is
      converted into stearic acid (C18:0) via carbon chain elongation. Here, we
      describe the cloning and expression of a rat hepatic enzyme, rELO2, responsible
      for the elongation of C16:0, presumably at the condensing reaction. Heterologous
      expression experiments in a yeast, Saccharomyces cerevisiae, demonstrated the
      elongation activity of rELO2 on C16:0 and to a lesser extent, C18:0 and fatty
      acids with low desaturation degree. This was distinct from that rELO1, a rat
      homolog of HELO1, which preferably catalyzed the elongation of mono- and
      polyunsaturated fatty acids of C16-C20. The Northern analysis showed that the
      expression of rELO2, but not rELO1, in hepatocytes was activated by the cycles of
      fasting and refeeding rats on a fat-free diet. Under these conditions, the rELO1
      was expressed constitutively in various tissues but the rELO2 transcripts were
      detected predominantly in liver.

PMID- 12005058
TI  - Biotransformation of L-lysine to L-pipecolic acid catalyzed by L-lysine 6
      aminotransferase and pyrroline-5-carboxylate reductase.
AB  - The enzyme involved in the reduction of delta1-piperideine-6-carboxylate (P6C) to
      L-pipecolic acid (L-PA) has never been identified. We found that Escherichia coli
      JM109 transformed with the lat gene encoding L-lysine 6-aminotransferase (LAT)
      converted L-lysine (L-Lys) to L-PA. This suggested that there is a gene encoding
      "P6C reductase" that catalyzes the reduction of P6C to L-PA in the genome of E.
      coli. The complementation experiment of proC32 in E. coli RK4904 for L-PA
      production clearly shows that the expression of both lat and proC is essential
      for the biotransformation of L-Lys to L-PA. Further, We showed that both LAT and
      pyrroline-5-carboxylate (P5C) reductase, the product of proC, were needed to
      convert L-Lys to L-PA in vitro. These results demonstrate that P5C reductase
      catalyzes the reduction of P6C to L-PA. Biotransformation of L-Lys to L-PA using
      lat-expressing E. coli BL21 was done and L-PA was accumulated in the medium to
      reach at an amount of 3.9 g/l after 159 h of cultivation. It is noteworthy that
      the ee-value of the produced pipecolic acid was 100%.

PMID- 12005059
TI  - Construction of protease-deficient Candida boidinii strains useful for
      recombinant protein production: cloning and disruption of proteinase A gene
      (PEP4) and proteinase B gene (PRBI).
AB  - The yeast Candida boidinii PEP4 and PRB1 genes, encoding proteinase A (PrA) and
      proteinase B (PrB), respectively, have been cloned and their primary structures
      were analyzed. The open reading frames of the PEP4 gene (1263 bp encoding a
      protein of 420 amino acids) and the PRBI gene (1683 bp encoding a protein of 560
      amino acids) were found. The deduced amino acid sequences of PrA and PrB are very
      similar to Saccharomyces cerevisiae PrA and PrB (64% and 61% identities,
      respectively). Both PEP4 and PRBI genes were disrupted in the C. boidinii genome
      by one-step gene disruption. The resultant pep4delta and the pep4delta prb1delta
      strains lost protease activity when compared with the wild-type original strain.
      The constructed C. boidinii strains are expected to be useful hosts for
      heterologous protein production.

PMID- 12005060
TI  - Isolation and characterization of cbbL and cbbS genes encoding form I ribulose
      1,5-bisphosphate carboxylase/oxygenase large and small subunits in Nitrosomonas
      sp. strain ENI-11.
AB  - The cbbL and cbbS genes encoding form I ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RubisCO) large and small subunits in the ammonia-oxidizing
      bacterium Nitrosomonas sp. strain ENI-11 were cloned and sequenced. The deduced
      gene products, CbbL and CbbS, had 93 and 87% identity with Thiobacillus
      intermedius CbbL and Nitrobacter winogradskyi CbbS, respectively. Expression of
      cbbL and cbbS in Escherichia coli led to the detection of RubisCO activity in the
      presence of 0.1 mM isopropyl-beta-D-thiogalactopyranoside (IPTG). To our
      knowledge, this is the first paper to report the genes involved in the carbon
      fixation reaction in chemolithotrophic ammonia-oxidizing bacteria.

PMID- 12005061
TI  - Enzymatic synthesis of oligosaccharide containing Le(x) unit by using partially
      purified chicken serum.
AB  - Animal sera were screened for an alternative enzyme source of alpha1,3
      fucosyltransferase, and the highest activity was observed in chicken serum. A
      partially purified enzyme fraction almost devoid of coexisting glycosidases was
      prepared from the chicken serum, and used for the fucosylation of LacNAc
      compounds. The enzyme reaction was efficient enough to allow the one-pot
      preparation of designed Le(x) compounds such as LNFP III.

PMID- 12005062
TI  - Radical scavenging activities of niacin-related compounds.
AB  - We investigated whether niacin-related compounds had radical-scavenging activity
      by electron spin resonance methods. Many compounds, but not trigonelline, had
      radical-scavenging activity against hydroxyl radicals. However, for the nitric
      oxide radical and 1,1-diphenyl-2-picrylhydrazyl radical, only nicotinic acid
      hydrazide and isonicotinic acid hydrazide had scavenging activities. These
      results suggest that the moiety of hydrazide might have an important role in
      scavenging abilities of various radicals.

PMID- 12005063
TI  - Spectroscopic evidence that salicylic acid converts a temporally inactivated form
      of horseradish peroxidase (compound III) to the irreversibly inactivated
      verdohemoprotein (P-670).
AB  - We obtained spectroscopic evidence in support of salicylate-dependent
      inactivation of horseradish peroxidase-C. Addition of salicylate to the enzyme
      arrested at a temporal inactive state (Compound III) in the presence of H2O2,
      resulted in rapid and irreversible inactivation of the enzyme yielding
      verdohemoproteins (P-670). Multiple roles for salicylate in peroxidase-catalyzed
      reactions are discussed.

PMID- 12005064
TI  - Spectroscopic evidence in support of horseradish peroxidase compound II-catalyzed
      oxidation of salicylic acid but not of phenylethylamine.
AB  - Salicylic acid and phenylethylamine are putative substrates for naturally
      occurring reactions for generation of reactive oxygen species, which are
      catalyzed by plant peroxidases. Here, we used commercially available highly
      purified horseradish peroxidase-C (HRP-C) as a model enzyme for spectroscopic
      analysis, and obtained data suggesting that the Compound II form of HRP-C does
      not utilize phenylethylamine as substrate. In contrast, addition of salicylic
      acid to Compound II resulted in rapid conversion of Compound II to the native
      form.

PMID- 12005065
TI  - Myrsinoic acids B, C and F, anti-inflammatory compounds from Myrsine seguinii.
AB  - The methanolic extract of Myrsine seguinii yielded three anti-inflammatory
      compounds, myrsinoic acids B, C and F, and their structures were elucidated from
      the spectroscopic data. These compounds suppressed the TPA-induced edema of mouse
      ear, myrsinoic acid F being the most active (IE 77% at a dose of 0.56 micromol).

PMID- 12005066
TI  - Enantioselective synthesis of both enantiomers of dimethyl cis-(4
      acetoxycyclopent-2-enyl)malonate, key intermediates for epijasmonate.
AB  - Both enantiomers (3 and 4) of dimethyl cis-(4-acetoxycyclopent-2-enyl)malonate
      (3), known intermediates for the synthesis of epijasmonate, were prepared in an
      enantio-enriched form from common starting material 2 based on desymmetrization
      of the meso-character by palladium-catalyzed asymmetric allylic alkylation.

PMID- 12005067
TI  - Identification of a putative vacuolar serine protease gene in the rice blast
      fungus, Magnaporthe grisea.
AB  - We identified and cloned a gene designated SPM1, encoding a serine protease from
      the rice blast fungus Magnaporthe grisea. SPM1 is a single-copy gene, encoding a
      subtilisin-like serine protease with 536 amino acids. Analyses of the deduced
      amino acid sequence of SPM1 suggested that SPM1 would be localized in a vacuole,
      an important organelle in pathogenicity.

PMID- 12005068
TI  - Statistical analysis of the relationship between translation initiation AUG
      context and gene expression level in humans.
AB  - The preference for the optimal nucleotide of the mammalian translation initiation
      AUG context [GCCGCC(A/G)CCaugG] is generally more pronounced in the highly
      expressed genes than in the transcription factor genes at the -9 through -1
      positions in humans. The influence of amino acid preference on the nucleotide
      choice at the +4 position was also examined.

PMID- 12005069
TI  - Preparation of the addition products of alpha-tocopherol with cholesteryl
      linoleate-peroxyl radicals.
AB  - a-Tocopherol was reacted with cholesteryl linoleate hydroperoxides (Ch18:2-OOH)
      in the presence of an iron-chelate, Fe(III) acetylacetonate, at 37 degrees C in
      benzene. The reaction products were isolated and identified as four positional
      isomers of cholesteryl (8a-dioxy-alpha-tocopherone)-epoxyoctadecenoates and two
      positional isomers of cholesteryl (8a-dioxy-alpha-tocopherone)-octadecadienoates.
      The result indicates that the peroxyl radicals from Ch18:2-OOH react with the 8a
      carbon radical of alpha-tocopherol to form the addition products.

PMID- 12005070
TI  - Functional expression in Aspergillus oryzae of p15, a protein with potent neurite
      inducing activity in PC12 cells.
AB  - We previously reported that a fungal protein, p15, induces neurite outgrowth and
      differentiation of rat pheochromocytoma PC12 cells through the activation of the
      Ca2+ signaling pathway. We report here the secretory production of p15 in
      Aspergillus oryzae. Analysis of culture supernatant of A. oryzae transformed with
      the gene encoding the p15 precursor tagged with a hemagglutinin (HA) epitope
      demonstrated that the transformant secreted a protein with an apparent molecular
      mass of 17.5 kDa, which is a little larger than the expected size of mature p15
      HA. By heat denaturation and ion exchange chromatography, p15-HA was easily
      purified from the culture supernatant with sufficient abundance. Although
      purified p15-HA was less active than the native p15 obtained from the culture
      broth of a producing fungal strain, it had neurite-inducing activity in PC12
      cells in a dose-dependent manner, providing a system to study the action
      mechanism of p15.

PMID- 12005071
TI  - Isolation and identification of a new bifidogenic growth stimulator produced by
      Propionibacterium freudenreichii ET-3.
AB  - We have found a new growth stimulator for bifidobacteria in the culture broth of
      Propionibacterium freudenreichii ET-3. The bifidogenic growth stimulator (BGS)
      was purified by Diaion HP-20 column chromatography and preparative HPLC.
      Spectroscopic methods including 1H-NMR, UV, and LC-ESI-MS experiments indicated
      that the chemical structure of the bifidogenic growth stimulator was 1,4
      dihydroxy-2-naphthoic acid (DHNA). Approximately 10 mg/L of DHNA was found to be
      produced in the culture broth of P. freudenreichii ET-3.

PMID- 12005072
TI  - Requirement for C-terminal extension to the RNA binding domain for efficient RNA
      binding by ribosomal protein L2.
AB  - Ribosomal protein L2 is a primary 23S rRNA binding protein in the large ribosomal
      subunit. We examined the contribution of the N- and C-terminal regions of
      Bacillus stearothermophilus L2 (BstL2) to the 23S rRNA binding activity. The
      mutant desN, in which the N-terminal 59 residues of BstL2 were deleted, bound to
      the 23S rRNA fragment to the same extent as wild type BstL2, but the mutation
      desC, in which the C-terminal 74 amino acid residues were deleted, abolished the
      binding activity. These observations indicated that the C-terminal region is
      involved in 23S rRNA binding. Subsequent deletion analysis of the C-terminal
      region found that the C-terminal 70 amino acids are required for efficient 23S
      rRNA binding by BstL2. Furthermore, the surface plasmon resonance analysis
      indicated that successive truncations of the C-terminal residues increased the
      dissociation rate constants, while they had little influence on association rate
      constants. The result indicated that reduced affinities of the C-terminal
      deletion mutants were due only to higher dissociation rate constants, suggesting
      that the C-terminal region primarily functions by stabilizing the protein L2-23S
      rRNA complex.

PMID- 12005073
TI  - Phytotoxic sesterterpene, 11-epiterpestacin, from Bipolaris sorokiniana NSDR-011.
AB  - The structure of siccanol, a phytotoxic sesterterpene of fungal origin, was
      analyzed after chemical conversion by NMR spectroscopy. Siccanol was found to be
      an epimer of terpestacin that has been isolated from Arthrinium sp., and was thus
      renamed 11-epiterpestacin. Its stereochemistry was also identical with that of
      fusaproliferin, a structurally related mycotoxin from Fusarium proliferatum.
      Therefore, this sesterterpene may also be referred to as 24-deacetyl
      fusaproliferin. The phytotoxicity of 11-epiterpestacin was almost equal to that
      of terpestacin, but significantly higher than that of fusaproliferin.

PMID- 12005074
TI  - Luteolin, a flavone, does not suppress postprandial glucose absorption through an
      inhibition of alpha-glucosidase action.
AB  - In order to clarify the postprandial glucose suppression via alpha-glucosidase
      (AGH) inhibitory action by natural compounds, flavonoids were examined in this
      study. Among the flavonoids (luteolin, kaempferol, chrysin, and galangin),
      luteolin showed the potent maltase inhibitory activity with the IC50 of 2.3 mM,
      while less inhibitions were observed against sucrase. In addition, the effects of
      maltase inhibition by flavonoids were observed in the descending order of potency
      of luteolin > kaempferol > chrysin > galangin. Apparently, the AGH inhibition
      power greatly increased with the replacement of hydroxyl groups at 3' and 4'
      position of the B-ring. However, the inhibitory power of luteolin was poorer than
      a therapeutic drug (acarbose: IC50; 430 nM). As a result of a single oral
      administration of maltose or sucrose (2 g/kg) in SD rats, no significant change
      in blood glucose level with the doses of 100 and 200 mg/kg of luteolin was
      observed. These findings strongly suggested that luteolin given at less than 200
      mg/kg did not possess the ability to suppress the glucose production from
      carbohydrates through the inhibition of AGH action in the gut.

PMID- 12005075
TI  - A simple method for enrichment of uninucleate conidia of Aspergillus oryzae.
AB  - Aspergillus oryzae produces multinucleate conidia, which makes the obtaining of
      homokaryons labor-intensive. Analysis of conidia by flow cytometry clarified the
      relationship that conidia of lower nuclear number were smaller in size. Based on
      this, we have developed a simple way to enrich uninucleate conidia with a
      membrane filter. Our results also suggest that the method is useful for
      elimination of heterokaryons.

PMID- 12005076
TI  - Synthesis of (1R,2S)-1-(3'-chloro-4' -methoxyphenyl)-1,2-propanediol (trametol)
      and (1R,2S)-1-(3',5'-dichloro-4'-methoxyphenyl)-1,2-propanediol, chlorinated
      fungal metabolites in the natural environment.
AB  - (1R,2S)-1-(3'-Chloro-4'-methoxyphenyl)-1,2propanediol (Trametol, 3), a metabolite
      of the fungus Trametes sp. IVP-F640 and Bjerkandera sp. BOS55, was synthesized by
      employing Sharpless asymmetric dihydroxylation as the key step. Similarly, the
      (1R,2S)-isomer of 1-(3',5'-dichloro-4'-methoxyphenyl)-1,2-propanediol (4),
      another metabolite of Bjerkandera sp. BOS55, was synthesized by asymmetric
      dihydroxylation.

PMID- 12005077
TI  - Milk basic protein (MBP) increases radial bone mineral density in healthy adult
      women.
AB  - We studied the effects of daily intake of milk basic protein (MBP) on radial bone
      mineral density (BMD) in healthy adult women. Thirty-three healthy women were
      randomly assigned to a 6-month trial with either placebo or MBP (40 mg per day).
      The radial BMD of each volunteer was measured at the beginning of and at six
      months after the trial. The mean BMD value at the 6th month in the MBP group
      increased significantly at both 1/6 and 1/10 portion from the distal end of the
      radius, whereas that in the control group did not. The BMD gain of each volunteer
      in the MBP group was significantly higher than that in the placebo group. Thus a
      daily MBP supplementation of 40 mg in healthy adult women can significantly
      increase radial BMD.

PMID- 12005078
TI  - Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine
      in low birth weight and preterm infants.
AB  - OBJECTIVE: To determine the efficacy, immunogenicity and safety of the
      heptavalent CRM197 pneumococcal conjugate vaccine (PCV) in low birth weight (LBW)
      and preterm (PT) infants against invasive pneumococcal disease caused by vaccine
      types. METHODS: In a randomized double blind trial of 37,868 infants given either
      PCV or meningococcal type C conjugate vaccine (MCV), 1756 infants <750 g <2500 g
      (LBW) and 4340 infants from 32 to <38 weeks old (PT) were identified. Risk of
      invasive pneumococcal disease in LBW and PT infants was compared with risk in
      normal birth weight (NBW) and full term (FT) infants. Local and systemic events
      observed within 48 h of recent vaccine were assessed by telephone interviews and
      similar comparisons made. Premature infant Emergency Department visits and
      hospitalization were also identified and compared with FT and NBW infants.
      RESULTS: Initiation of immunization and intervals between doses were similar for
      all groups. The risk ratio for invasive pneumococcal diseases for LBW infants
      compared with NBW infants was 2.6 (P = 0.03), and for PT compared with FT infants
      the risk ratio was 1.6 (P = 0.06). Vaccine efficacy for both groups was 100%. PCV
      was as immunogenic in LBW and PT as in NBW and FT infants. Fever and local events
      after PCV vaccination were similar when adjusted for clustering among multiple
      doses per child. When stratified for individual doses there was more redness and
      swelling for LBW infants and more swelling for PT infants after Dose 3. Isolated
      local and systemic reactions were more commonly seen with PCV than with MCV, a
      pattern similar to that in NBW and FT infants. Hospitalization rates were similar
      for PCV and MCV recipients. CONCLUSION: These data support the use of PCV in LBW
      infants and PT infants.

PMID- 12005079
TI  - Antibody response to pneumococcal capsular polysaccharides in children with acute
      otitis media.
AB  - BACKGROUND: To describe the antibody response to pneumococcal capsular
      polysaccharides in children <2 years of age with pneumococcal acute otitis media
      (AOM) caused by serotypes 6A, 6B, 11A, 14, 19F or 23F. These serotypes were
      commonly found in both nasopharyngeal carriage and AOM in children of the study
      population in Finland. METHODS: Serum antibody concentrations to pneumococcal
      capsular polysaccharides of types 6B, 11A, 14, 19F and 23F were measured by
      enzyme immunoassay in acute and convalescent sera from children with AOM.
      RESULTS: Responses (at least 2-fold increase of antibody concentration) were
      relatively infrequent and varied with both the age of the child and the serotype
      of the Streptococcus pneumoniae isolated from the middle ear fluid. Children
      older than 12 months were more likely to have antibody responses than were
      younger children. Responses were seen only infrequently to types 6A, 6B or 19F (1
      of 14, 1 of 9 and 2 of 25, respectively), more often to types 11A and 14 (2 of 8
      and 3 of 8) and relatively frequently to type 23F (8 of 18). However, the
      convalescent antibody concentrations to type 23F were low and usually declined
      after the infection, whereas responders to 14 AOM had antibodies that persisted
      at a high concentration through the follow-up. CONCLUSIONS: The results emphasize
      the differences between Streptococcus pneumoniae serotypes in their
      immunogenicity and quantitative and qualitative differences of antibodies
      produced after infection.

PMID- 12005080
TI  - Evaluation of diagnostic tests for influenza in a pediatric practice.
AB  - INTRODUCTION: Recent advances in the diagnosis and treatment of influenza virus
      infections include: (1) rapid bedside diagnosis methods with simple commercially
      available tests; and (2) Food and Drug Administration approval of treatment for
      children 1 year of age and older with neuraminidase inhibitor drugs. For proven
      benefit antivirals should be used within 2 days of onset of symptoms. OBJECTIVES:
      We conducted a performance improvement exercise comparing the sensitivity and
      specificity of four rapid tests for influenza viruses: (1) Flu OIA (Biostar); (2)
      Quickvue Influenza Test (Quidel); (3) Z Stat Flu (ZymeTx); and (4) Directigen Flu
      A (Becton Dickinson). METHODS: During the 1999 to 2000 epidemic, symptomatic
      patients seen at the private practice of one of the authors provided specimens
      collected and processed according to the manufacturer's directions. Throat swabs
      only were used to collect the specimens for the Z Stat Flu Kit. Directigen was
      performed immediately, and the others were run in parallel within 12 to 24 h.
      Specimens were frozen first at -20 degrees C for up to 3 days and shipped in
      transport medium to the Virology Research Laboratory of the Virginia State Health
      Department for culture where they were stored at -60 degrees C until cultured.
      Some of the samples were processed by a commercial laboratory. RESULTS: Specimens
      from 116 patients were available for influenza culture; for 88 of these culture
      was performed at the State Health Department Laboratory, and for 28 culture was
      performed at a local commercial medical laboratory. Influenza virus (A) was
      detected in 58 of 116 (50%) specimens, 10 (17%) of these only by direct
      fluorescent antigen samples. Viral culture-direct fluorescent antigen results
      were used as the standard. Of the 4 tests Biostar and Z Stat Flu required more
      technician time (by an average of 2-fold). The 4 tests had sensitivities ranging
      from 72 to 95%. Z Stat differed significantly in sensitivity from the other three
      (P = 0.001). The specificities of Directigen, Quickvue, Flu OIA and Z Stat Flu
      were similar (76 to 86%). The positive predictive value of Directigen, Quickvue
      and FluOIA and Z Stat ranged from 80 to 86%. The negative predictive value of all
      4 tests ranged from 75 to 94%. Z Stat Flu had a lower negative predictive value
      than the other 3 tests (75%; P = 0.001. CONCLUSION: In this first head-to-head
      comparison of four rapid diagnostic tests for influenza, Directigen Flu A,
      Quickvue and Flu OIA appear equivalent in sensitivity, specificity, positive
      predictive value and negative predictive value. Z Stat Flu was not as sensitive
      or as efficient as the other three tests.

PMID- 12005081
TI  - Outbreaks of influenza A virus infection in neonatal intensive care units.
AB  - BACKGROUND: Outbreaks of nosocomial influenza virus infections have been
      described rarely during childhood and even less so in the neonatal period.
      METHODS: We report 30 neonates admitted to 2 neonatal intensive care units with
      nosocomial influenza A virus infection, which occurred in 2 outbreaks during
      1999. Risk factors for infection were evaluated, and control measures were
      adopted. Virus was detected by indirect immunofluorescence antibody screen. Any
      infant with nasopharyngeal aspirate positive for influenza A virus was considered
      infected. RESULTS: Of 95 infants screened 30 were positive for influenza A virus
      (31.5%). Mean birth weight was 1622 g, and mean gestational age was 31 weeks in
      the infected group. In the noninfected group mean birth weight was 2594 g and
      mean gestational age was 36.4 weeks. Low birth weight, short gestational age,
      twin pregnancy and mechanical ventilation were identified as risk factors for
      infection. Clinical symptoms were seen in 22, and 8 were asymptomatic. Clinical
      features were predominantly respiratory and digestive. The outcome was favorable
      in all cases. CONCLUSIONS: Infection by influenza virus has to be considered as a
      possible cause of nosocomial infection in the neonatal period. Control measures
      and prevention are important.

PMID- 12005082
TI  - Interpretation of the tuberculin skin test reaction by pediatric providers.
AB  - BACKGROUND: The tuberculin (TB) skin test is widely used, but it is not easy to
      read. There are few data on how well pediatric care providers interpret the TB
      skin test or on the success of various methods used to read the skin test
      reaction. OBJECTIVE: To determine the ability of pediatric care providers to
      correctly read a positive TB skin test reaction and to identify the most
      successful method of measuring a TB skin test reaction. METHODS: Twenty nurses,
      16 staff pediatricians, 13 residents and 8 medical students who were working in a
      large pediatrics clinic were asked to read a 15-mm TB skin test reaction of a
      known converter. The study participants read the skin test using any technique
      they wished. The primary outcome measure was the percentage of providers who read
      the TB skin test as > or = 10 mm (considered a correct reading). RESULTS: Seventy
      seven percent (44 of 57) of the participants interpreted the TB skin test as > or
      = 10 mm, but 18% (10 of 57) of them read the skin test as negative (< or = 5 mm).
      The participants used a variety of interpretation techniques with 18 using the
      ballpoint pen technique. Participants who used the pen technique were
      significantly more likely to read the skin test as > or = 10 mm compared with
      those who used other methods (94% vs. 69%; P = 0.04). Pen technique users were
      also significantly less likely to measure the reaction as < or = 5 mm (0% vs.
      26%; P = 0.02). CONCLUSIONS: Many providers, regardless of professional training
      and experience, read a 15-mm TB skin test reaction as > or = 10 mm, but a
      significant minority interpreted it as negative. Use of the pen technique may
      decrease the number of false negative readings. Specific instruction on use of
      the pen technique to read TB skin tests should be incorporated into medical
      training curriculums.

PMID- 12005083
TI  - Cefepime versus ceftazidime as empiric monotherapy for fever and neutropenia in
      children with cancer.
AB  - BACKGROUND: Monotherapy with cefepime or ceftazidime is an effective alternative
      to combination therapy for the treatment of febrile neutropenic adult cancer
      patients. We compared the efficacy and safety of cefepime and ceftazidime as
      empiric monotherapy of febrile neutropenia in children with cancer. MATERIALS AND
      METHODS: A prospective, open label, randomized, comparative study in pediatric
      cancer patients was conducted at Chang Gung Children's Hospital from January 1,
      2000, to April 15, 2001. Patients with fever and neutropenia (absolute neutrophil
      count of < or = 500/mm3) were randomized to receive either intravenous cefepime
      or ceftazidime (50 mg/kg/dose as two or three doses daily). Febrile episodes were
      classified as microbiologically documented infection, clinically documented
      infection or unexplained fever. Clinical response to therapy was classified as
      success and failure. RESULTS: Ninety-five pediatric cancer patients with 120
      febrile neutropenic episodes were randomized to receive empiric treatment with
      cefepime or ceftazidime. After 72 h of treatment, 82.8% (48 of 58) of the
      eligible patients in the cefepime group continued with unmodified therapy,
      compared with 87.9% (51 of 58) in the ceftazidime group. The neutrophil count was
      <100/mm3 at randomization for 76% of the patients in the cefepime group and 83%
      of those in the ceftazidime group; the median durations of neutropenia (<500/mm3)
      were 8.5 and 6.5 days, respectively. Of the 96 evaluable episodes the overall
      success rate with unmodified empiric therapy until the end of the treatment
      course in the cefepime group was comparable with that in the ceftazidime group
      (69% vs. 71%, P = 0.95). The response rate after glycopeptides were added to the
      regimens was 79.2% for the cefepime group and 77.1% for the ceftazidime group.
      The bacterial eradication rate was 33% for the cefepime group and 20% for the
      ceftazidime group (P = 0.85), and the rates of new infections were 10.4% vs. 4.2%
      (P = 0.67), respectively. Both study drugs were well-tolerated. Three (6.4%)
      patients in the cefepime group and 2 (4.3%) patients in the ceftazidime group
      died. CONCLUSION: Cefepime appeared to be as effective and safe as ceftazidime
      for empiric treatment of febrile episodes in neutropenic pediatric cancer
      patients.

PMID- 12005084
TI  - Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in
      infants.
AB  - BACKGROUND: Serogroup C meningococcal conjugate polysaccharide vaccines have been
      reported to induce significant serum IgG antibodies and immunologic memory in
      infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx,
      local mucosal immune responses may play an important role in host defense against
      infection and carriage. We have investigated the mucosal IgA and IgG antibody
      responses to two meningococcal C conjugate vaccines in the saliva of healthy
      infants. METHODS: Specific salivary IgA and IgG antibodies to two meningococcal C
      polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and
      Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in
      infants after parenteral vaccinations at the ages of 2, 3 and 4 months.
      Unstimulated saliva samples were collected immediately before the first
      immunization and 1 month after the third immunizations. Forty healthy infants
      receiving the same routine vaccines but no meningococcal C vaccine were recruited
      as controls. RESULTS: There were significant increases in meningococcal C
      polysaccharide-specific IgG antibody concentrations postvaccination compared with
      prevaccination concentrations in both vaccinated groups (both P < 0.001), but no
      change in the control group. There were no significant increases in specific IgA
      postvaccination geometric mean concentrations in either the vaccine or the
      control groups. The number of IgA positives postvaccination increased slightly in
      the Wyeth vaccine group vs. controls (P < 0.05). CONCLUSIONS: Significant
      salivary IgG antibodies to meningococcal C polysaccharide were observed after
      parenteral immunization with two meningococcal C conjugate vaccines, whereas
      there was no significant increase in specific IgA antibody levels for these two
      vaccines.

PMID- 12005085
TI  - Resistance testing in children changing human immunodeficiency virus type 1
      protease inhibitor.
AB  - OBJECTIVE: To assess genotypic and phenotypic resistance testing in HIV-1
      infected children failing a first protease inhibitor (PI) therapy. METHODS: In a
      multicenter observational study 21 children, ages 3 to 16 years, were given two
      reverse transcriptase inhibitors and one PI (mainly ritonavir, n = 18). They were
      subsequently treated with single or dual PI-based therapy (predominantly
      nelfinavir, n = 10, or ritonavir-saquinavir, n = 7). Resistance testing was
      performed at the time of therapy switch via direct sequencing and a recombinant
      virus susceptibility assay. RESULTS: A total of 21 genotypic and 15 phenotypic
      resistance profiles were obtained. Most viruses displayed several reverse
      transcriptase mutations; however, 7 isolates maintained a wild-type protease.
      Ritonavir targeted the well-known pathway containing 82, 54, 46 and other
      secondary (nonactive site) mutations including T74A. No in vitro cross
      resistance, i.e. > or = 8-fold resistance to saquinavir or amprenavir, was
      encountered. Secondary mutations enhanced the prediction of ritonavir resistance
      (i.e. L10I) and in vitro nelfinavir cross-resistance (i.e. K20R/I) conferred by
      primary (active site) resistance mutations. Either the 82, 54, 46 mutational
      genotype or the phenotype showing > or = 8-fold nelfinavir cross-resistance
      predicted a poorer virologic response to nelfinavir salvage therapy. CONCLUSION:
      In a small cohort of heavily pretreated pediatric patients, resistance testing
      appears to predict the response to nelfinavir as salvage for a ritonavir-based
      therapy. This is further supported by the correlation between ritonavir-selected
      mutations and in vitro nelfinavir cross-resistance. Prospective studies should
      assess clinical outcome in children undergoing regimen changes based on
      resistance testing.

PMID- 12005086
TI  - Clinical presentations of rotavirus infection among hospitalized children.
AB  - BACKGROUND: Although rotaviruses (RVs) are the most common cause of severe
      gastroenteritis in children, there is a lack of information detailing the
      spectrum of clinical manifestations of RV disease resulting in hospitalization.
      OBJECTIVE: To characterize the clinical spectrum of RV-associated
      hospitalizations, including short stay visits in children. METHODS: Active RV
      disease surveillance was conducted at three children's hospitals Sundays through
      Thursdays in children 15 days through 4 years of age admitted with diarrhea (D),
      vomiting (V) and/or unexplained fever (F) between November, 1997, and June, 1998.
      Stool specimens were collected and tested for RV by enzyme immunoassay. RESULTS:
      Of the 862 children enrolled, 763 (88%) had a stool specimen tested for RV.
      Overall 31% of children excreted RV. RV excretion was highest when all 3 symptoms
      (D, V and F) occurred in the same child (56%), lower when 2 symptoms occurred
      together (38% DV; 19% DF; 13% VF) and lowest when each symptom occurred alone (3%
      D; 11% V; 6% F). Nine percent of the children without diarrhea excreted RV.
      Children admitted without diarrhea were more likely to have rotavirus if they
      developed diarrhea during their hospitalization. CONCLUSIONS: RV detection was
      greatest when diarrhea, vomiting and fever occurred together and lowest when each
      symptom occurred alone. The spectrum of symptoms of rotavirus disease in children
      at the time of admission to the hospital or short stay unit may be broader than
      previously recognized.

PMID- 12005087
TI  - Infections diagnosed in the first year after pediatric stem cell transplantation.
AB  - BACKGROUND: Cumulative incidence of infections in the first year
      posttransplantation in adult patients has been well-described. Such description
      is less than complete for pediatric stem cell transplantation (SCT) patients.
      Further among those patients who have been infected, analysis of risk factors for
      infection has not been well-described for a large cohort of pediatric SCT
      patients. METHODS: We conducted a retrospective cohort study of infections in the
      first year after SCT at Duke University Medical Center. We recorded all
      infections in the first year after transplantation. We determined incidences for
      6 categories of infection: gram-negative rods; gram-positive cocci; yeast
      species; Aspergillus sp.; adenovirus; and cytomegalovirus. We determined
      incidences based on type of transplant and days post transplantation. We also
      completed bivariable and multivariable analysis of risk factors [neutropenia,
      graft vs. host disease (GVHD) and GVHD treatment] for infection type among those
      children who were infected. RESULTS: We evaluated 510 transplants in 485
      children. There were 584 infections in the first year after transplantation.
      During the first 30 days posttransplantation, type of transplantation did not
      predict incidence of infection or type of infection. After 30 days children who
      received unrelated cord blood transplant and matched unrelated donor transplant
      were at much higher risk of infection than were patients who received autologous,
      matched sibling or haploidentical transplant (P < 0.001). Patients who received
      unrelated cord blood or matched unrelated donor transplantation were at higher
      risk of aspergillosis (P = 0.002), candidiasis (P = 0.005) and adenovirus (P <
      0.0001) but not cytomegalovirus (P = 0.18). In analysis of risk factors among
      those infected, patients with aspergillosis were more likely to have severe GVHD:
      multivariable 1 year risk ratio, 7.5; 95% confidence interval, 3.0, 18.4.
      Neutropenia was more strongly associated with gram-negative rod infection than
      any other type of infection. CONCLUSIONS: The incidence of infection immediately
      after transplantation did not differ significantly by type of transplant in this
      pediatric population. Type of transplant predicted increased incidence of
      infection 30 days posttransplantation and increased incidence of infection with
      several organisms traditionally associated with a high mortality rate in the
      transplant population.

PMID- 12005088
TI  - Comparison of two gentamicin dosing schedules in very low birth weight infants.
AB  - BACKGROUND: Several dosing schedules for gentamicin have been recommended for
      very low birth weight infants during the early neonatal period. We conducted a
      prospective, randomized, controlled trial to compare efficacy and
      pharmacokinetics of two dosing schedules in preterm neonates. METHODS: Fifty
      eight very low birth weight infants (600 to 1500 g), prescribed gentamicin for
      treatment of suspected sepsis during the first week after birth, were randomized
      to receive either the new dosing schedule [every 48 h (q48h)] or the existing
      dosing schedule [every 24 h (q24h)]. Infants in the "q48h" group received
      gentamicin at 5.0 or 4.5 mg/kg/dose q48h depending on weight group and infants in
      the "q24h" group received 2.5 or 3.0 mg/kg/dose q24h. Peak and trough serum
      gentamicin concentrations were monitored. RESULTS: Peak serum gentamicin
      concentrations after the first dose were significantly higher in the q48h infants
      than in q24h infants (8.19 +/- 1.3 vs. 6.04 +/- 2.2, P = 0.00001). Ninety percent
      of all peak serum gentamicin concentrations in the q48h group were in a higher
      therapeutic range of 6 to 12 microg/ml as compared with 55% of q24h (P = 0.0005).
      None of the q48h infants had subtherapeutic serum gentamicin concentrations
      immediately after administration of the first dose as compared with 36% of q24h
      infants (P < 0.005). Eighteen percent of q24h infants continued to have peak
      serum gentamicin concentrations in subtherapeutic range even after the third dose
      at 48 h. Trough serum gentamicin concentrations were significantly lower in q48h
      infants than in q24h infants. However, 9 of 30 (30%) q48h infants had trough
      serum gentamicin concentrations of < or = 0.5 microg/ml before the dose at 48 h
      and 4 of the 9 had serum gentamicin concentrations of <1 microg/ml at 24 h after
      the first dose. CONCLUSIONS: The q48h dosing schedule of gentamicin given to very
      low birth weight infants during the first week after birth achieved therapeutic
      serum gentamicin concentrations and potentially higher peak to MIC ratios for
      microorganisms in all infants. However, nearly one-third of the infants had
      extremely low serum gentamicin concentrations before the next dose. A dosing
      interval of 36 h might be optimal for bactericidal activity and avoid bacterial
      growth during prolonged periods of extremely low serum gentamicin concentrations;
      this dosing interval warrants study.

PMID- 12005089
TI  - Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive
      fungal infections in children.
AB  - OBJECTIVE: To describe the safety and efficacy of voriconazole in children
      treated within the compassionate release program. METHODS: Children received
      voriconazole on a compassionate basis for treatment of an invasive fungal
      infection if they were refractory to or intolerant of conventional antifungal
      therapy. Voriconazole was administered as a loading dose of 6 mg/kg every 12 h
      i.v. on Day 1 followed by 4 mg/kg every 12 h i.v. thereafter. When feasible the
      route of administration of voriconazole was changed from i.v. to oral (100 or 200
      mg twice a day for patients weighing < 40 or > or = 40 kg, respectively). Outcome
      was assessed by investigators at the end of therapy or at the last visit as
      success (complete or partial response), stable infection, or failure, based on
      protocol-defined criteria. RESULTS: Sixty-nine children (ages 9 months to 15
      years; median, 7 years) received voriconazole; 58 had a proven or probable fungal
      infection. Among these 58 patients 27 had hematologic malignancies and 13 had
      chronic granulomatous disease as the most frequent underlying conditions. Forty
      two patients had aspergillosis, 8 had scedosporiosis, 4 had invasive candidiasis
      and 4 had other invasive fungal infections. The median duration of voriconazole
      therapy was 93 days. At the end of therapy 26 patients (45%) had a complete or
      partial response. Four patients (7%) had a stable response, 25 (43%) failed
      therapy and 4 (7%) were discontinued from voriconazole because of intolerance.
      Success rates were highest in patients with chronic granulomatous disease (62%)
      and lowest in patients with hematologic malignancies (33%). Two patients
      experienced treatment-related serious adverse events (ulcerated lips with rash,
      elevated hepatic transaminases or bilirubin). A total of 23 patients had
      voriconazole-related adverse events, 3 (13%) of which caused discontinuation of
      voriconazole therapy. The most commonly reported adverse events included
      elevation in hepatic transaminases or bilirubin (n = 8), skin rash (n = 8),
      abnormal vision (n = 3) and a photosensitivity reaction (n = 3). CONCLUSION:
      These data support the use of voriconazole for treatment of invasive fungal
      infections in pediatric patients who are intolerant of or refractory to
      conventional antifungal therapy.

PMID- 12005090
TI  - Malaria infection does not appear to modify the risk of bronchiolitis early in
      life.
AB  - BACKGROUND: The observation of an increased prevalence of allergic disorders
      coinciding with a decreasing frequency of infectious diseases in early childhood
      has led to the speculation that infections may prevent allergic sensitization.
      Information on the role of parasites in this context is limited. Bronchiolitis in
      infancy has been linked with asthmatic symptoms later in childhood, although the
      underlying cause of this association is unknown. METHODS: To test the hypothesis
      that early parasitic infections in infancy might prevent the development of
      allergic manifestations later in life, the effect of malaria infections during
      the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian
      children at 18 months of age. The study was conducted as part of an intervention
      trial of malaria chemoprophylaxis and/or iron supplementation for the prevention
      of malaria and anemia in infants. RESULTS: The incidence of bronchiolitis up to
      18 months of age in the 675 children was 0.58 episode per child per year. The
      risk factors analysis was based on 470 children with complete data. There was no
      difference in the incidence of bronchiolitis between those who had received
      malaria chemoprophylaxis during the first year of life and those who had not.
      However, the proportion of children who had bronchiolitis was lower among those
      who had had malaria episodes than among those who had not (48% vs. 55%, P =
      0.05). CONCLUSIONS: This study does not support the hypothesis that reduced
      exposure to parasites may modulate the development of bronchiolitis early in
      life.

PMID- 12005091
TI  - Starry, starry night.

PMID- 12005092
TI  - Combination vaccines.

PMID- 12005093
TI  - Infectious disease issues in internationally adopted children.

PMID- 12005094
TI  - Failure to thrive and history of pneumocystis carinii pneumonia in a six-year-old
      Hispanic boy.

PMID- 12005095
TI  - Xanthomas and hyperlipidemia in a human immunodeficiency virus-infected child
      receivng highly active antiretroviral therapy.
AB  - An 8-year-old perinatally HIV-infected boy developed xanthomas secondary to
      highly active antiretroviral therapy-induced hyperlipidemia. This is a phenomenon
      previously not reported in HIV-infected children. The case illustrates the
      difficulty in managing an emerging complication, extreme hyperlipidemia, in
      children receiving highly active antiretroviral therapy because of limited
      pediatric experience with lipid-lowering agents and the likely need for lifelong
      treatment.

PMID- 12005096
TI  - Characterization of Klebsiella pneumoniae and Escherichia coli strains that
      produce CTX-M-2-type broad spectrum beta-lactamase isolated from a child with
      leukemia.
AB  - An 8-year-old girl with acute leukemia had bacteremia caused by Klebsiella
      pneumoniae producing CTX-M-2-type broad spectrum beta-lactamase. K. pneumoniae
      and Escherichia coli strains producing the same enzyme and harboring identical
      conjugative plasmids were recovered from stoor culture. Patients with frequent
      episodes of neutropenia and prophylactic administration of beta-lactams are at
      risk of harboring colonizing strains that produce broad spectrum beta-lactamases.

PMID- 12005097
TI  - Fatal disseminated Candida lusitaniae infection in an infant with chronic
      granulomatous disease.
AB  - A 3-month-old boy born to a mother carrying an X-linked form of chronic
      granulomatous disease presented with persistent fever and hepatosplenomegaly. The
      diagnosis was confirmed as a gp91phox defect by genetic analysis, and the patient
      was managed with broad spectrum antibacterial agents, gamma-interferon and later
      amphotericin B. A liver biopsy revealed granulomata with budding yeast forms, and
      cultures of blood and urine grew Candida lusitaniae. The patient died 26 days
      after admission.

PMID- 12005098
TI  - Tularemia of the middle ear.
AB  - We report the case of a 10-year-old boy with prolonged fever who was found to
      have tularemia of the middle ear. Otolaryngologic cases including oropharyngeal
      and glandular or ulceroglandular forms of the head and neck region are estimated
      to account for 12% of all tularemia cases, but to date we have not seen a report
      of tularemia in the middle ear. The possibility of tularemia may not occur to a
      physician because of the wide variation of clinical manifestations.

PMID- 12005099
TI  - Endocarditis caused by Staphylococcus lugdunensis.
AB  - We describe a case of native valve endocarditis caused by Staphylococcus
      lugdunensis, a perineal skin commensal, and review 28 other cases from the
      medical literature. Correctly identifying this coagulase-negative organism is
      critical because endocarditis is usually associated with left sided valvular
      disruption and life-threatening embolic complications, reminiscent of disease
      caused by Staphylococcus aureus. Urgent surgical intervention is necessary in
      most cases.

PMID- 12005100
TI  - Neonatal porcine pancreatic cell clusters as a potential source for
      transplantation in humans: characterization of proliferation, apoptosis,
      xenoantigen expression and gene delivery with recombinant AAV.
AB  - Neonatal porcine islets are characterized by reproducible isolation success and
      high yields, sizable advantages over adult islets. In this work we have analyzed
      selected phenotypic and functional characteristics of porcine neonatal islets
      relevant to their possible use for transplant in humans. We show that porcine
      islet cells proliferate in culture, and synthesize and store islet-specific
      hormones. Proliferating beta cells can be easily identified. Implant of cultured
      neonatal islets in immunodeficient rodents results in the reversal of diabetes,
      albeit with delay. We also show that measurable apoptosis occurs in cultured
      neonatal porcine islets. Further, antigens recognized by human natural antibodies
      are expressed in a dynamic fashion over the culture period analyzed and are not
      limited to the alpha-Gal epitope. Lastly, we demonstrate that a recombinant Adeno
      Associated virus can be used to efficiently deliver a reporter gene in porcine
      islets. This characterization might be helpful in the definition of the potential
      use of neonatal porcine islets for human transplantation.

PMID- 12005101
TI  - Rapid failure of pig islet transplantation in non human primates.
AB  - We have previously demonstrated that adult pig islets of Langerhans are not
      destroyed in vitro by primate sera. Whether these islets can function when placed
      into the liver of non-human primates is not known. We now report on the outcome
      of pig islet xenotransplantation into five non diabetic primates (four baboons
      and one macacus fascicularis) receiving intraportally purified adult pig islets.
      The average number of islet-equivalent per graft was 110,000 (60-180,000). All
      animals received associations of ATG, cyclosporine or LF 195 (a deoxyspergualin
      analog), mycophenolate mofetil and corticosteroids. A specific porcine C-peptide
      (C-pep) RIA test was used to monitor insulin secretion. Two hours after grafting,
      porcine C-peptide was positive (from 0.37 to 4.25 ng/ml) in all monkeys except
      one. Primate C-pep was normal in all cases. Only two monkeys had detectable
      levels of porcine C-pep on day 1 or 2 with undetectable levels thereafter, even
      after glucagon challenge between days 6 and 10. Several normal islets with
      moderate inflammatory infiltration were observed in one animal liver on day 2
      (the time of necropsy) as well as islets with IgM and complement deposition.
      Among animals sacrificed on days 14, 16 and 38, some residual islet cells could
      be identified only in livers collected on day 14. Partial glycaemic control was
      achieved in some rats receiving islets from the same preparations. In conclusion,
      adult pig islets are not able to maintain insulin secretion for more than 24 h
      when injected intraportally into non diabetic immunosuppressed monkeys.
      suggesting immediate islet xenograft destruction.

PMID- 12005102
TI  - Adult porcine islet transplantation in baboons treated with conventional
      immunosuppression or a non-myeloablative regimen and CD154 blockade.
AB  - The aim of the present study was to assess the survival of adult porcine islets
      transplanted into baboons receiving either (I) conventional triple drug
      immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154
      monoclonal antibody (mAb) aimed at tolerance-induction. Group 1 baboons (n = 3)
      were pancreatectomized prior to intraportal injection of 10,000 porcine islet
      equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG),
      cyclosporine and azathioprine. In Group 2 (n = 2), non-pancreatectomized baboons
      underwent induction therapy with whole body and thymic irradiation, and ATG.
      Extracorporeal immunoadsorption (EIA) of anti-Galalpha1,3Gal (Gal) antibody was
      carried out. Maintenance therapy was with cobra venom factor, cyclosporine.
      mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were
      injected intraportally (14,000 and 32,000 IE/kg, respectively) and high-dose pig
      mobilized peripheral blood progenitor cells (3 x 10(10) cells/kg) were infused
      into a systemic vein. Porcine islets were also implanted in the sternomastoid
      muscle to facilitate subsequent biopsies. In both groups. porcine C-peptide was
      measured, and histological examination of liver or sternomastoid muscle biopsies
      was performed at regular intervals. In Group 1, total pancreatectomy reduccd
      human C-peptide to < 0.1 ng/ml and induced insulin-requiring diabetes. The
      transplantation of porcine islets was followed by normalization of glycemia for
      15-24 h. Porcine C-peptide was detected only transiently immediately after
      porcine islet injection (maximum 0.12 ng/ml). Histological examination of liver
      biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic
      cell structures with mononuclear cell infiltrates were identified in portal
      venules. In Group 2, injection of porcine islets into non-pancreatectomized
      recipients induced a transient hypoglycemia (2-4 h) requiring concentrated
      intravenous dextrose administration. Porcine C-peptide was detectable for 5 and 3
      days (maximum 2.8 and 1.0 ng/ml), respectively. Baboon #4 died on day 12 from
      small bowel intussusception. Liver and sternomastoid muscle biopsies showed well
      preserved porcine islets, staining positive for insulin and glucacon, without
      signs of rejection. In baboon #5, viable islets were detected in the
      sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A
      progressive mononuclear cell and macrophage infiltration was seen in the
      biopsies. In conclusion, conventional immunosuppression allowed survival of
      porcine islets in baboons for < 24 h. The non-myeloablative regimen prolonged
      survival of porcine islets for > 14 days. However, despite depletion of T cells,
      anti-Gal antibody and complement, and CD154-hlockade, porcine islets were
      rejected by day 28. These results suggest that powerful innate immune responses
      are involved in rejection of discordant xenogencic islets.

PMID- 12005103
TI  - HDAF transgenic pig livers are protected from hyperacute rejection during ex vivo
      perfusion with human blood.
AB  - The aim of this study was to determine if human decay-accelerating factor (hDAF)
      protects against hyperacute rejection in an ex vivo liver perfusion system using
      human blood. Pig livers were perfused ex vivo via the portal vein for an average
      of 5-6 h using a membrane oxygenator. Three groups were studied. Group I: Wild
      type pig livers were alloperfused with fresh pig blood (n = 5). Group II: Wild
      type pig livers were xenoperfused with fresh human blood (n = 5). Group III: hDAF
      transgenic pig livers were xenoperfused with fresh human blood (n = 5). The graft
      ischemic time, ratio of perfusate volume to liver weight, flow rate, and
      perfusate hematocrit were similar in each group. The hDAF livers perfused with
      human blood (Group III) had a lower ALT level, less protein and albumin losses,
      lower bilirubin levels in the perfusate, less weight gain, and greater bile
      production than the wild-type livers perfused with human blood. Histology showed
      classic features of hyperacute rejection in Group II, including massive
      hemorrhage, severe vasculitits, fibrin and C5b-9 deposition, and endothelial
      damage within 1 h of perfusion, whereas liver histology studies in Groups I and
      III were near normal. IgG and IgM deposits were seen in the xenoperfused livers.
      Electron microscopy (EM) and immuno-EM showed loss of endothelial cells, trapping
      of white blood cells and platelets, and diffuse fibrin deposits in Group II only.
      hDAF pig livers perfused with human blood showed superior function and histology
      when compared with wild-type pig livers. These data suggest that (1) hyperacute
      rejection may contribute to the inconsistent results using wild-type pig livers
      for extracorporeal liver support and (2) genetically modified pigs that express
      hDAF may provide a better donor source than wild-type pigs for extracorporeal
      liver support.

PMID- 12005104
TI  - Transgenic pigs designed to express human CD59 and H-transferase to avoid humoral
      xenograft rejection.
AB  - Research in pig-to-primate xenotransplantation aims to solve the increasing
      shortage of organs for human allotransplantation and develop new cell- and tissue
      based therapies. Progress towards its clinical application has been hampered by
      the presence of xenoreactive natural antibodies that bind to the foreign cell
      surface and activate complement, causing humoral graft rejection. Genetic
      engineering of donor cells and animals to express human complement inhibitors
      such as hCD59 significantly prolonged graft survival. Strategies to decrease the
      deposition of natural antibodies were also developed. Expression of human
      alpha1,2-fucosyltransferase (H transferase, HT) in pigs modifies the cell-surface
      carbohydrate phenotype resulting in reduced Galalpha1,3-Gal expression and
      decreased antibody binding. We have developed transgenic pigs that coexpress
      hCD59 and HT in various cells and tissues to address both natural antibody
      binding and complement activation. Functional studies with peripheral blood
      mononuclear cells and aortic endothelial cells isolated from the double
      transgenic pigs showed that coexpression of hCD59 and HT markedly increased their
      resistance to human serum-mediated lysis. This resistance was greater than with
      cells transgenic for either hCD59 or HT alone. Moreover, transgene expression was
      enhanced and protection maintained in pig endothelial cells that were exposed for
      24 h to pro-inflammatory cytokines. These studies suggest that engineering donor
      pigs to express multiple molecules that address different humoral components of
      xenograft rejection represents an important step toward enhancing xenograft
      survival and improving the prospect of clinical xenotransplantation.

PMID- 12005105
TI  - Human adrenocortical cell xenotransplantation: model of cotransplantation of
      human adrenocortical cells and 3T3 cells in scid mice to form vascularized
      functional tissue and prevent adrenal insufficiency.
AB  - To establish an experimental model for replacement of endocrine organ function by
      xenotransplantation, human adrenocortical cells from postnatal donors were
      transplanted beneath the kidney capsule of adrenalectomized scidmice together
      with mitomycin C-treated 3T3 cells that secrete FGF. Adrenocortical cells from
      seven donors, male and female, ranging from 6-50 years of age, were used. 12 of
      13 animals survived > 16 days following surgery. After 50 days they were
      sacrified to allow assessment of the histology and ultrastructure of tissue
      formed from the transplanted cells. Only 1 of 23 adrenalectomized sham-operated
      animals survived > 16 days. In all surviving animals, vascularized adrenocortical
      tissue formed at the site of transplantation. Cortisol, the normal human
      glucocorticoid, was present in the plasma of these animals, replacing
      corticosterone, the mouse glucocorticoid. Some animals, but not most, had
      measurable aldosterone. The tissue formed from the transplanted cells showed
      histological and ultrastructural features of normal adrenal cortex. Mitochondria
      had tubulo-vesicular cristae and there were prominent microvilli between cells.
      Tissues had a well-developed vasculature, sometimes with large sinusoidal
      vessels. Proliferation in the transplant tissues was very low. These results show
      that tissue formed from transplanted human adrenocortical cells is able to
      replace the essential functions of the adrenal gland in scid mice. This
      demonstrates that transplanted human endocrine cells can functionally replace a
      surgically removed endocrine organ in a host animal.

PMID- 12005106
TI  - Simultaneous inhibition of B7 and LFA-1 signaling prevents rejection of
      discordant neural xenografts in mice lacking CD40L.
AB  - Transplantation of embryonic human neural tissue can restore dopamine
      neurotransmission and improve neurological function in patients with Parkinson's
      disease. Logistical and ethical factors limit the availability of human embryonic
      allogeneic tissue. Embryonic xenogeneic neural tissue from porcine donors is an
      alternative form of donor tissue, but effective immunomodulatory techniques are
      warranted for neural xenotransplantation to become clinically feasible. We
      transplanted embryonic porcine ventral mesencephalic tissue into the brains of
      adult untreated C57BL/6 mice, untreated CD40L-/-mice and CD40L-/-mice that
      received injections of anti-LFA-1, CTLA41g or both compounds. Double-treated
      CD40L-/-mice had large grafts with high numbers of dopaminergic neurons 4 wk
      after transplantation. The grafts were completely devoid of lymphocytes,
      macrophages and activated microglia. Untreated C57BL/6 mice had rejected their
      grafts. Untreated CD40L-/-mice and CD40L-/-mice treated with monotherapy of anti
      LFA-1 or CTLA41g had smaller grafts and more microglial and lymphocytic
      infiltration than double-treated CD40L-/-mice. We conclude that immunomodulation
      with concomitant inhibition of LFA-1 and B7 signaling in the perioperative period
      in CD40L-/-mice prevented the rejection of discordant neural xenografts. The
      treatment most likely reduced antigen presenting capacity and interfered with the
      costimulatory signaling needed for T cell activation to occur.

PMID- 12005107
TI  - Counteraction of the rapid tolerance to 8-hydroxy-2-(di-n-propylamino)tetralin
      induced hypothermia in rats by activation of the GABAA receptor-chloride channel
      complex.
AB  - The effects of compounds that open the GABAA receptor-chloride channel complex on
      the rapidly developed tolerance to the 8-hydroxy-2-(di-n-propylamino)tetralin
      hydrobromide(8-OH-DPAT)-induced hypothermia in rats were examined. The test
      compound was injected 15 min. before 1 mg/kg subcutaneous 8-OH-DPAT or saline and
      24 hr later a challenge dose of 0.1 mg/kg subcutaneous 8-OH-DPAT was given. The
      rectal temperature was measured before the challenge dose and 30, 60, 90 and 120
      min. thereafter. The hypothermic effect was calculated as the area under the
      curve. It was found that all the GABAergic compounds examined significantly
      counteracted the 8-OH-DPAT-induced tolerance to the hypothermic response:
      muscimol at 3 mg/kg subcutaneous, diazepam at 1 - 3 mg/kg subcutaneous,
      pentobarbitone sodium at 20 mg/kg subcutaneous, and chlormethiazole at 40 mg/kg
      subcutaneous. Combined treatment of the rats with the GABAA receptor antagonist,
      bicucculine, or the GABAA receptor-chloride channel blocker, picrotoxin and
      diazepam, pentoparbitone sodium or chlormethiazole significantly antagonised this
      counteraction of the 8-OH-DPAT-induced tolerance. Depletion of 5-HT by
      pretreatment of the rats with the tryptophan hydroxylase inhibitor p
      chlorophenylalanine did not counteract the 8-OH-DPAT-induced tolerance to the
      hypothermic response. Pretreatment of the rats with dexamethazone did not change
      the development of the tolerance to 8-OH-DPAT-induced hypothermic effect which
      seems to exclude the involvement of the hypothalamo-pituitary-adrenocortical axis
      in the tolerance development. It is concluded that the results support the
      hypothesis that GABA neurones beyond the 5-HT neurones are involved in the
      mechanism causing tolerance to the 5-HT1A receptor-mediated hypothermia in rats.

PMID- 12005108
TI  - Prenatal phencyclidine induces heightened neurodegeneration in rats in some brain
      regions, especially during 2nd trimester, but possible anti-apoptotic effects in
      others.
AB  - Phencyclidine administered to the developing rat brain at high doses for a few
      hours during late foetal life induces apoptotic neurodegeneration in several
      brain regions. We sought to investigate whether prolonged, low level foetal
      exposure to phencyclidine during different gestational periods (2nd trimester
      versus 3rd trimester) would have different effects on several brain regions
      showing neurodegeneration as assessed using silver stains. Pregnant rats were
      treated with phencyclidine (5.45 mg/day) continuously for 5 days via minipumps,
      and the pups were either perfused immediately after birth and silver-stained for
      degeneration, or allowed to mature and then tested for behavioural deficits. In
      the newborn pups, there was a substantial increase in the number of agrophilic
      cells in entorhinal cortex and subiculum; this effect was greater when the drug
      was given during 2nd trimester. However, in the ventromedial nucleus of the
      hypothalamus, both the 2nd and 3rd trimester phencyclidine pups had significantly
      fewer degenerating cells than the controls. Behavioural tests of rotorod and open
      field performance in the pups allowed to mature indicated decreased motor
      coordination and hyperactivity in the 3rd trimester phencyclidine pups, but
      minimal alterations in the 2nd trimester pups. Thus, prenatal exposure to
      phencyclidine can have either neurodegenerative or antiapototic effects depending
      upon brain region, and there is a discrepancy between persisting behavioural
      deficits and amount of cell loss for time of maximal prenatal effect of the drug.

PMID- 12005109
TI  - Changes in markers of oxidative stress and membrane properties in synaptosomes
      from rats exposed prenatally to toluene.
AB  - The present study was undertaken in order to investigate if toluene induced
      oxidative stress in brains from rats exposed prenatally to 1800 ppm toluene 6
      hr/day at days 7-20 during the pregnancy. 35-42 days after birth the rats were
      killed and synaptosomal fractions were prepared for the experiments. Synaptosomes
      from rats exposed prenatally to toluene exhibited an increased level of oxidative
      stress when incubated with toluene in vitro compared to synaptosomes from
      unexposed offspring. Also the cell membrane was affected, as the calcium leakage
      was more increased from exposed synaptosomes than from unexposed. The membrane
      fluidity increased significantly when synaptosomes were incubated with toluene
      for 10 min. in vitro but the change in fluidity was identical in both groups of
      offspring. The results indicate that prenatal exposure to toluene induces long
      lasting changes in oxidative status and membrane function.

PMID- 12005110
TI  - The preclinical observation that escitalopram possesses a faster time to onset of
      efficacy than citalopram.

PMID- 12005111
TI  - Inhibitory effect of melatonin on homocysteine-induced lipid peroxidation in rat
      brain homogenates.
AB  - Oxidative damage is implicated in several pathologies including cardiovascular
      disease. As a model system to study the response of cells to oxidative insults,
      homocysteine toxicity was examined since it is an independent risk factor for
      atherosclerotic disease. The levels of malondialdehyde and 4-hydroxyalkenals were
      assayed as an index of oxidatively damaged lipid. In in vitro experiments, the
      increase of lipid peroxidation products induced by homocysteine were
      concentration- and time-dependent. To study the protective effect of melatonin on
      homocystine induced lipid peroxidation, brain homogenates were treated with
      different concentrations of melatonin. The accumulation of malondialdehyde and 4
      hydroxyalkenals induced by homocysteine was significantly reduced by melatonin in
      a concentration-dependent manner. Additionally, a melatonin concentration of 1.5
      mM reduced the levels of oxidatively damaged lipid products below those measured
      in control homogenates (no homocysteine, no melatonin). These data suggest that
      melatonin, an endogenous antioxidant may have a role in protecting cells from
      oxidative damage due to homocysteine and they support the idea that
      pharmacological concentrations could be used as a therapeutic agent in reducing
      cardiovascular disease where homocysteine may be a causative or contributing
      agent.

PMID- 12005112
TI  - Acetaminophen induces a caspase-dependent and Bcl-XL sensitive apoptosis in human
      hepatoma cells and lymphocytes.
AB  - Acetaminophen is a widely used analgesic and antipyretic drug that exhibits
      toxicity at high doses to the liver and kidneys. This toxicity has been
      attributed to cytochrome P-450-generated metabolites which covalently modify
      target proteins. Recently, acetaminophen, in its unmetabolized form, has been
      shown to affect a variety of cells and tissues, for instance, testicular and
      lymphoid tissues and lymphocyte cell lines. The effects on cell viability of
      acetaminophen at a concentration comparable to that achieved in plasma during
      acetaminophen toxicity have now been examined with a hepatoma cell line SK-Hep1,
      primary human peripheral blood lymphocytes and human Jurkat T cells.
      Acetaminophen reduced cell viability in a time-dependent manner. Staining of
      cells with annexin-V also revealed that acetaminophen induced, after 8 hr of
      treatment, a loss of the asymmetry of membrane phospholipids, which is an early
      event associated with apoptosis. Acetaminophen triggered the release of
      cytochrome c from mitochondria into the cytosol, activation of caspase-3, 8, and
      9, cleavage of poly(ADP-ribose) polymerase, and degradation of lamin B1 and DNA.
      Whereas cleavage of DNA into internucleosomal fragments was apparent in
      acetaminophen treated SK-Hep1 and primary lymphocytes, DNA was only degraded to
      50-kb fragments in treated Jurkat cells. Overexpression of the antiapoptotic
      protein Bcl-XL prevented these various apoptotic events induced by acetaminophen
      in Jurkat cells. Caspase-8 activation was a postmictochondrial event and occurred
      in a Fas-independent manner. These results demonstrate that acetaminophen induces
      caspases-dependent apoptosis with mitochondria as a primary target. These results
      also reiterate the potential role of apoptosis in acetaminophen hepatic and
      extrahepatic toxicity.

PMID- 12005113
TI  - Relevance of multidrug resistance proteins for intestinal drug absorption in
      vitro and in vivo.
AB  - Multidrug resistance proteins (p-glycoprotein and mrps) are becoming increasingly
      important to explain the pharmacokinetics and action of drugs. Located in
      epithelial and endothelial cells of the gastrointestinal tract, liver, kidney,
      blood brain barrier, choroid plexus and other organs, they are critical
      determinants for the movement of a large number of commonly prescribed drugs
      across cellular barriers. Here we provide a brief overview of the role of
      multidrug resistance proteins in drug absorption from the gastrointestinal tract.
      We address the different types of multidrug resistance proteins involved,
      describe experimental models to study the influence of these proteins on
      transcellular transport and discuss the impact of multidrug resistance proteins
      on overall drug bioavailability in vivo.

PMID- 12005114
TI  - Occlusion vs. skin barrier function.
AB  - BACKGROUND/AIMS: Skin occlusion may increase percutaneous absorption of applied
      chemicals, with some exceptions. It also obstructs the normal ventilation of the
      skin surface and increases stratum corneum hydration and hence compromises skin
      barrier function. METHODS/RESULTS: This review focuses the effects of occlusion
      on skin barrier function, in particularly, as defined with objective skin
      bioengineering technology. CONCLUSIONS: The effects of occlusion on skin barrier
      function have been defined with various techniques. Optimal hydrocolloid
      materials can absorb excess water and reduce the unfavourable effects of
      occlusion.

PMID- 12005115
TI  - Hydration vs. skin permeability to nicotinates in man.
AB  - BACKGROUND/AIMS: Prolonged skin occlusion increases stratum corneum water content
      and often increases skin permeability and irritant dermatitis. As skin wetness
      from wearing diapers is considered an important factor favouring the onset of
      diaper dermatitis, optimal diapering might decrease skin hyperhydration and
      dermatitis. Our aim is to define the quantitative relationship between nicotinate
      ester (a model penetrant) skin permeability and hydration, as measured by water
      evaporation rate (WER), decay curves (at individual time points) and WER-area
      under the curve (WER-AUC); and also to determine the level of skin hydration and
      skin permeability to nicotinates following a diapering simulation.
      METHODS/RESULTS: Nine healthy Caucasian adult women were enrolled after a
      prescreening procedure (time to peak redness response to nicotinate); each
      received three wet occlusive patches for different exposure times (10 min, 30
      min, and 3h) and two wet model diapers (3 and 8 h). Prior to patching or
      diapering of forearms, basal values of WER, skin blood flow volume (BFV),
      capacitance (Cap) and redness (a*) were measured on premarked sites (a, b, c and
      d). Immediately, following occlusive patch or diaper removal, 20 microL of each
      nicotinate (methyl and hexyl nicotinate) was applied to its respective site (a or
      b). The WER and Cap readings were recorded at designated sites (c and d) with the
      following intervals after nicotinate applications: 0, 5,10,15 and 20 min. The a*
      and BFV measurements were made on each nicotinate challenged site (a and b) with
      the following intervals after nicotinate applications: 5, 10, 15, 20, 30, 40, and
      60 min. RESULTS: WER-AUC and thus, skin hyperhydration, increased with occlusive
      patch and diaper exposure time, but there was no statistical difference between 3
      and 8h diaper sites. All patched sites had significantly (P<0.05) increased
      hydration in comparison to control sites (undiapered or unpatched skin). Cap
      increased with occlusion time with patches, but not with diapers. The degree and
      time-course of redness from nicotinates did not vary with extent of skin
      hydration, but was significantly increased compared to non-hydrated skin. BFV-AUC
      did not show a significant increase between diapers at 3 and 8h sites; the BFV
      AUC values varied on the patched sites, but some were significantly (P<0.05)
      higher than control site. CONCLUSION: Wet patches and diapers increased skin
      hyperhydration proportional to exposure time. Permeation of nicotinates was
      increased for hydrated skin vs. control, even after only 10 min of patch
      exposure. For these model permeants, we found no evidence of increased permeation
      rates with increased hyperhydration, once a relatively low threshold of
      hyperhydration was achieved (e.g. that reached after a 10 min wet patch). The
      data showed no meaningful differences in permeation following either diapering
      simulation and also suggested that the WER-AUC method was superior to capacitance
      for measuring the absolute extent of hyperhydration. We believe this is a
      suitable model for evaluating the quality of diaper product performance, as well
      as in pharmacologic assays of occlusive therapy.

PMID- 12005116
TI  - The influence of body mass index on skin susceptibility to sodium lauryl
      sulphate.
AB  - BACKGROUND: The influence of nutrition on the physiological functions of man is
      well studied. Numerous diseases can be exacerbated by obesity. However, it has
      not yet been determined whether body weight and body mass index (BMI), as an
      indicator of a high body fat store, can influence skin sensitivity. OBJECTIVE:
      This study investigates the correlation between body mass index and the epidermal
      functions, evaluated by bioengineering methods, before and after an irritant
      patch test with sodium lauryl sulphate (SLS). METHODS: Epidermal functions were
      evaluated using an evaporimeter, chromameter and laser-Doppler-flowmeter. Patch
      testing was conducted for 48 h with two different concentrations of SLS (0.25%
      and 0.5%) on the forearms of healthy volunteers. Measurements were performed 24h
      after patch removal. RESULTS: Obese individuals showed significantly increased
      transepidermal water loss (TEWL), skin blood flow and skin colour (red) as
      compared to a control group. However, the degree of skin sensitivity to SLS was
      not correlated with BMI. CONCLUSION: Basal biophysical parameters of the skin are
      primarily correlated with the BMI. This may be caused by obesity-induced
      physiological changes, e.g. increased sweat gland activity, high blood pressure
      and physiological temperature-regulating system. The epidermal barrier function,
      as evaluated after SLS patch testing is, however, not correlated with a high BMI,
      indicating a normal skin barrier.

PMID- 12005117
TI  - Skin irritation typing and grading based on laser Doppler perfusion imaging.
AB  - BACKGROUND/AIMS: Vasodilation with increased cutaneous perfusion is an essential
      part of an irritant inflammatory response. The aim of the present study was to
      investigate the usefulness of the high-resolution laser Doppler perfusion imaging
      (HR-LDPI) technique for investigating irritant skin reactions. Irritants may
      elicit clinically different reactions due to different skin penetration profiles
      and different modes of irritant action on the exposed METHODS: Twelve subjects
      were tested on the forearms using 24 h occlusive application of three
      concentrations of the irritants sodium lauryl sulphate (SLS) and nonanoic acid
      (NON) and with the topical acne drug all-trans retinoic acid (RA). Cutaneous
      blood flow at baseline, the increase in cutaneous blood flow and the skin area
      having increased perfusion were measured on day 2, day 3 and day 5. RESULTS:
      Based both on measurement of mean perfusion and area with increased perfusion, it
      was possible to differentiate between different clinical irritation grades on any
      study day. The area with increased perfusion exceeded the area with clinically
      visible skin reactions for irritant reactions of grade 1/2 and above. Irritant
      reactions for individual irritants could furthermore be typed using HR-LDPI. It
      was possible to differentiate between vehicle treatment and the different dose
      levels of the irritant compounds. A correlation was found between clinical scores
      for the individual irritants and the mean flow and the area with increased flow.
      The individual irritants could be differentiated due to different time courses of
      their skin irritation. CONCLUSION: Laser Doppler imaging was found to be an
      important new method for characterization and grading of the inflammatory
      response of single exposure irritant reactions. However, standardised study
      procedures cannot be emphasised enough in order to obtain reliable and useful
      data.

PMID- 12005118
TI  - Studies of cutaneous blood flow of normal forearm skin and irritated forearm skin
      based on high-resolution laser Doppler perfusion imaging (HR-LDPI).
AB  - BACKGROUND/AIMS: High resolution laser Doppler perfusion imaging (HR-LDPI) is a
      non-touch method used for mapping cutaneous microcirculation. The aim of the
      present study was to investigate the usefulness of this technique for studies of
      cutaneous blood flow of normal untreated forearm skin and for the assessment of
      weak irritant reactions induced by exposure to sodium lauryl sulphate (SLS).
      METHODS: 12 healthy volunteers participated in the study. Initially, basal flow
      was measured for 6 selected test areas on the right forearm. 24h occlusive
      application of 0%; 0.125%; 0.25%; 0.50% and 1.0% SLS was performed. An untreated
      skin area was also included. Test sites were clinically evaluated and the
      cutaneous blood flow was measured using HR-LDPI on days 2, 3 and 5. RESULTS AND
      CONCLUSIONS: The results of the present study show that HR-LDPI is a useful
      technique for assessing the mean cutaneous blood flow of both normal and
      irritated forearm skin. The rectangular region of interest (R-ROI) method was
      found to be superior to the threshold region of interest (T-ROI) method in image
      analysis of the mean blood flow of individual scans. The results showed that even
      though spatial variation within a skin region may be considerable, no
      intraregional differences or daily variations in mean basal flow of selected skin
      areas on the forearm could be found. Due to the low variability, it should not
      generally be necessary to include an untreated control site as each site should
      act as its own control. The temporal variation in skin perfusion was minor
      compared with the spatial variation. This was found both for normal and irritated
      skin. Therefore, one scan of each area of interest should normally be sufficient.
      Clinical irritation scores on day 3 were more evenly distributed than those on
      days 2 and 5. An increase in mean perfusion, as a function of the clinical
      irritation score, was found. However, no statistical differences could be found
      in mean perfusion for the selected dose levels of SLS.

PMID- 12005119
TI  - The evaluation of skin friction using a frictional feel analyzer.
AB  - BACKGROUND/AIMS: Sensory evaluation is an important factor for cosmetic products.
      Several devices for the measurement of sensory properties have been developed in
      recent years. The objective here is to measure skin surface friction using these
      devices and examine the correlation with other physiological parameters in order
      to evaluate the potential of physical measurement of tactile sensation. METHODS:
      A KES-SE Frictional Analyzer, a commercial device for measurement of surface
      frictional characteristics, was used in this study. An arm holder was added to
      this device for measurement on the human forearm. The frictional coefficient
      (MIU) and its mean deviation (MMD) were used as the parameter to indicate surface
      friction. The moisture content in the stratum corneum was measured with a
      Corneometer CM825, the transepidermal water loss with a Tewameter TM210, the
      viscoelastic properties of the skin with a Cutometer SEM575 and the skin surface
      pattern by observing the negative replica using silicon rubber. RESULTS: The MIU
      was not influenced by load; however, it was increased due to water application on
      the skin. The relationship between MIU and the moisture content in the stratum
      comeum, between MMD and skin surface pattern and between MMD and viscosity of
      both normal human forearm skin and SDS (sodium dodecyl sulfate)-induced dry skin
      were confirmed by statistical analysis in a test on human subjects. There was
      also a correlation between either MIU or MMD and sensory evaluation in the
      morning after the application of moisturizing products. CONCLUSION: Human skin
      surface friction was measured by using a KES-SE Frictional Analyzer. Judging from
      the correlation between either MIU or MMD and sensory evaluation, we considered
      this instrumental analysis to be useful for evaluating the tactile impression of
      human skin.

PMID- 12005120
TI  - Age related changes of human skin investigated with histometric measurements by
      confocal laser scanning microscopy in vivo.
AB  - BACKGROUND/AIMS: The confocal laser scanning microscope Vivascope (Lucid,
      Henrietta) allows skin to be studied in real-time with a resolution of 0.5 microm
      horizontal and 1.3 microm vertical in vivo. In this study, we present the results
      of a comparison between the skin of an older and a younger group of volunteers by
      in vivo histometric measurements. METHODS: To investigate changes caused by age,
      13 young (18-25years) and 13 older (>65years) volunteers were examined. The
      following parameters were measured using the Vivascope at the volar forearm:
      minimal thickness of the epidermis (E(min)), size of cells in the granular layer
      (A(gran)), thickness of the horny layer (DSC), thickness of the basal layer (DSB)
      and number of dermal papillae per area (Papl). The image analysis program image
      tool was used to measure the size of the cells and the thickness of the basal
      layer. RESULTS: The older group of volunteers showed a significant increase in
      E(min), no significant change in DSC, a significant decrease in dermal papillae
      and in the thickness of the basal layer, and an increase in A(gran) compared to
      the younger group. CONCLUSIONS: Histometric measurements by in vivo confocal
      laser scanning microscopy are a sensitive and non-invasive tool for
      characterizing and quantifying histological changes of the epidermis and
      papillary dermis due to ageing.

PMID- 12005121
TI  - Bioengineering methods employed in the study of wound healing of sulphur mustard
      burns.
AB  - BACKGROUND/PURPOSE: Sulphur mustard (SM) is a potent incapacitating chemical
      warfare agent that remains a threat to war fighters and civilians worldwide. SM
      lesions may require weeks or months to heal, depending upon their severity. This
      study was undertaken to find a treatment regimen that promotes speedier healing
      of deep cutaneous SM burns in a weanling pig model. The principal objective of
      the study was to compare four treatment regimens and establish which achieved the
      shortest healing time. METHODS: Twelve Yorkshire Cross weanling pigs were exposed
      to SM liquid for 2h, generating six large deep dermal/full thickness burns on the
      ventrum of each animal. Three additional animals served as sham-exposed controls.
      Surgical intervention occurred at 48 h postexposure. Treatments included: (i)
      full-thickness debridement of the burns with a computer controlled, raster
      scanned continuous wave CO2 laser followed by autologous split-thickness skin
      grafting; (ii) full-thickness sharp surgical tangential excision followed by skin
      grafting, the 'Gold Standard' used in human deep dermal/full-thickness thermal
      burns management; (iii) partial-thickness laser ablation with no grafting; and
      (iv) partial-thickness sharp surgical excision with no grafting. Several non
      invasive bioengineering methods were used to monitor the progress of wound
      healing throughout a 36-day healing period: reflectance colourimetry,
      evaporimetry, laser Doppler perfusion imaging and ballistometry. RESULTS:
      Bioengineering methods indicated that laser debridement followed by autologous
      split-thickness skin grafting was as efficacious in improving the wound healing
      of deep SM burns in weanling swine as the 'Gold Standard.' Regardless of the
      method of debridement, barrier function, skin colour and mechanical properties
      returned to near-normal levels within 15 days of treatment in the grafted sites.
      Regardless of surgical approach, blood flux levels remained approximately 50-60%
      of normal tissue throughout the 36-day postsurgical observation period. Mid
      dermal debridement by sharp surgical tangential excision or laser ablation
      without the use of skin grafts did not produce as good a result as those attained
      through the use of grafts, but was better than no surgical treatment of the
      wounds. CONCLUSION: Bioengineering methods were useful in evaluating multiple
      characteristics during wound healing: (i) reflectance colourimetry for skin
      colour, (ii) evaporimetry to measure transepidermal water loss as an indicator of
      barrier function, (iii) laser Doppler perfusion imaging to assess cutaneous blood
      flow, and (iv) ballistometry to measure the mechanical properties of skin
      hardness and elasticity. Perhaps the most useful method was evaporimetry, as a
      restored barrier function was the best indicator of healed wounds. The use of
      reflectance colourimetry and ballistometry will continue in future wound healing
      studies for their contributions in judging cosmetic and functional outcomes.
      While useful, laser Doppler perfusion imaging was found to be rather time
      consuming. This methodology will be limited in the future to burn depth
      estimation prior to treatment, and for evaluation of pharmaceuticals specifically
      designed to improve or sustain blood flow into damaged areas.

PMID- 12005122
TI  - A portable device using a closed chamber system for measuring transepidermal
      water loss: comparison with the conventional method.
AB  - BACKGROUND/AIM: The measurement of transepidermal water loss (TEWL) is frequently
      used to evaluate the barrier function of the stratum corneum (SC) of diseased
      skin in vivo, as well as normal skin damaged by external injurious agents. For
      this purpose, most people use biophysical instruments, based on an open chamber
      system, measuring the water vapor pressure gradient produced above the skin
      surface by vapor passing through the SC barrier. Recently, we tested a new
      portable device (Model H4300 NIKKISO-YSI CO., LTD., Tokyo, Japan) based on a
      closed chamber system. Its measuring principle is based on a computed TEWL
      estimation, from the progressive increase in relative humidity inside a closed
      chamber, due to continuous water evaporation from the skin surface on which the
      chamber is placed. METHODS: We conducted an in vivo comparative study between the
      new portable device and a conventional method, using the DermaLab (Cortex
      Technology, Hadsund, Denmark), on both healthy and diseased skin surfaces, under
      well-controlled, standardized, experimental conditions (21 degrees C and 50%
      relative humidity). RESULTS: We found that the sensitivity of the new device was
      similar to that of the DermaLab. For example, the poor SC barrier function of
      normal facial skin was clearly demonstrated by significantly higher TEWL values
      than those of the extremities (P<0.0001). The compromised barrier function of the
      lesional skin of atopic dermatitis and psoriasis was also demonstrated in a
      severity-dependent fashion. However, the TEWL values measured with the new device
      were much lower than those obtained with the DermaLab, probably reflecting
      differences in the methodological principles. Nevertheless, they correlated well
      with those of the latter method (P<0.001). For the instruments compared in the
      present study, we found the following equation useful for conversion:
      [corresponding value obtained with the DermaLab]= 1.42 x [the recorded value with
      Nikkiso-YSI Model H4300] + 1.892. CONCLUSIONS: We consider this closed chamber
      system practical because it can be carried easily and its portability enables
      TEWL measurements to be taken in any location, without ensuring a special
      environment against air turbulence. Moreover, it is far less expensive than other
      devices currently available.

PMID- 12005123
TI  - A field evaluation of the impact of transfer efficiency on worker exposure during
      spray painting.
AB  - This paper presents a mathematical model to predict breathing-zone overspray
      concentrations produced during spray painting as a function of the overspray
      generation rate, ventilation and work practices. The overspray generation rate
      required an estimate of the spray gun transfer efficiency, which was provided by
      a previously developed mathematical model. These models were evaluated in the
      field under two different scenarios: first in a controlled environment that
      approximated the assumptions of models, and then under actual spray painting
      conditions. Results from the first test showed the model overestimated transfer
      efficiency, but the measured exposures and predicted exposures were not
      significantly different. During actual spray painting operations, all task
      exposures were within a factor of three of the model predictions, and there was
      no statistical difference between the measured and predicted values. The
      predicted average exposure of each worker was within the 95% confidence interval.
      The overall mean exposure was within one standard error of the model prediction.
      The current study expands on the original exposure model by including a transfer
      efficiency model to provide a better estimate of the overspray generation rate.
      The theoretical foundation between exposure and its primary determinants is
      established, and this knowledge can be applied to design and can evaluate optimal
      control interventions. Also, the general methodology presented here for
      developing an exposure model is applicable to operations other than spray
      painting.

PMID- 12005124
TI  - Effect of sampling time on the culturability of airborne fungi and bacteria
      sampled by filtration.
AB  - Air sampling of bioaerosols by filtration may be preferable for many
      epidemiological studies because the methods can be used to collect personal
      samples for a full work-shift. There is some concern, however, that the viability
      of fungal spores and bacterial cells might be compromised by sampling for as long
      as a full shift. This study was designed to determine the effect of sampling up
      to 6 h on the viability (measured by culture) of airborne fungi and bacteria at
      composting facilities. Six side-by-side samples were collected in two locations
      at each of three composting facilities for 1 h at 2 l/m on polycarbonate filters.
      Two samples in each set were then capped while clean, HEPA-filtered air was drawn
      across two others for an additional 2 h and across the last two for an additional
      5 h. Filters were washed and the samples were analyzed for culturable bacteria
      and fungi, and for total bacteria and fungi by microscopic counting.
      Concentrations ranged from 1.7 x 10(3) to 6.2 x 10(7) c.f.u./m3 of culturable
      fungi and 1.17 x 10(4) to 1.0 x 10(6) c.f.u./m3 of culturable bacteria. In linear
      models that included duration of sampling, location, and the interaction of
      location and sample duration, neither sample duration nor the interaction term
      were significant predictors of the logs of the concentrations of culturable fungi
      or bacteria or of the ratio of the logs of the culturable concentrations to total
      concentrations for fungi or bacteria. This suggests that increased sampling time
      does not affect the viability of the organisms commonly found in the air at
      composting facilities.

PMID- 12005125
TI  - The development of process-specific risk assessment and control in Germany.
AB  - After reading the series of articles on a new approach to controlling chemicals,
      an initiative targeted especially on small and medium-sized businesses, in the
      Annals of Occupational Hygiene (1998; 42: 355-411), German specialists for health
      and safety at work realized that problems in this area are very similar in the UK
      and Germany. Also, in Germany different institutions have developed an array of
      solutions to help small and medium-sized enterprises during recent years. In this
      paper, we present these activities and hope to promote an international
      discussion about practical support for work with chemical substances.

PMID- 12005126
TI  - The quantitative risks of mesothelioma and lung cancer in relation to asbestos
      exposure: the Wittenoom data.

PMID- 12005127
TI  - Seasonal variations in injury rates during US Army Basic Combat Training.
AB  - OBJECTIVES: Previous literature suggests that injury rates during physical
      activity may be higher in the summer than in the fall or winter, possibly due to
      the greater amount or intensity of physical activity in the summer. This study
      examined seasonal differences in injury incidence during US Army Basic Combat
      Training, where physical activity was similar at all times of the year. METHODS:
      Four independent groups of subjects (total n = 1543 men and 1025 women) were
      investigated, two training in the summer and two training in the fall. Injury
      data were obtained from a retrospective review of the subjects' medical records
      at the conclusion of the 8 week training program. RESULTS: For men, the corrected
      relative risk of suffering an injury or a time loss injury in the summer was,
      respectively, 2.0 [95% confidence interval (CI) = 1.7-2.4] and 2.5 (95% CI = 1.9
      3.0) times higher than in the fall. For women, the corrected relative risk of
      suffering an injury or time-loss injury in the summer was, respectively, 1.4 (95%
      CI = 1.3-1.6) and 1.7 (95% CI = 1.5-2.0) times higher than in the fall. These
      risks were essentially unchanged after adjustment for subject physical
      characteristics (age, stature, body mass, body mass index) and physical fitness
      (push-ups, sit-ups and 2 mile run), indicating that the summer season was an
      injury risk factor independent of these variables. Linear correlations (r-values)
      between maximal daily temperature and injury incidence ranged from 0.92 to 0.97,
      indicating a strong relationship between these two variables. CONCLUSIONS: These
      data suggest that injury incidence among physically active individuals is higher
      in the summer than in the fall and that environmental temperature may provide a
      partial explanation for this finding.

PMID- 12005128
TI  - From quartz hazard to quartz risk: the coal mines revisited.
AB  - Following the classification of quartz as a human carcinogen by the IARC, many
      standard-setting committees are currently trying to convert this hazard into
      their national or EU standards. Since human data to set a safe exposure limit for
      quartz are limited, we hypothesized that lung burden data on quartz in coal
      miners' lungs after lifetime exposure could be used to set a non-carcinogenic
      lung burden of quartz, and that this might be valid for other groups
      occupationally exposed to quartz. A review of data shows that lungs of coal
      miners with simple coal workers' pneumoconiosis (sCWP) typically contain up to 30
      g of dust, and in one specific study lung burdens between 0.7 and 1.7 g of quartz
      were associated with macules only, and no sCWP. Assuming independent actions of
      coal and quartz and no clearance of quartz, and sCWP as a prerequisite for lung
      cancer due to quartz exposure in coal mine dust, a simple kinetic approach was
      applied. A no observed adverse effect level (NOAEL) for quartz of between 0.03
      and 0.13 mg/m3 (40 yr exposure) is derived, but it is concluded that more refined
      physiologically based pharmacokinetic modelling is needed for a better estimate,
      also including interindividual differences in lung clearance. Considering the
      independent effects of, and the well-known interaction between coal and quartz,
      these data could be important to other workplaces with usual mixed-dust exposure.

PMID- 12005129
TI  - Seeing is believing.

PMID- 12005130
TI  - Control of occupational exposure to hexavalent chromium and ozone in tubular wire
      arc-welding processes by replacement of potassium by lithium or by addition of
      zinc.
AB  - Hexavalent chromium [Cr(VI)] and ozone are produced in many arc-welding
      processes. Cr(VI) is formed when welding with chromium-containing alloys and is a
      suspected carcinogen. Ozone is formed by the action of ultraviolet light from the
      arc on oxygen and can cause severe irritation to the eyes and mucous membranes.
      Previous work has demonstrated that reduction of sodium and potassium in manual
      metal arc-welding electrodes leads to substantial reductions in Cr(VI)
      concentrations in the fume as well as a reduction in the fume formation rate. In
      this paper replacement of potassium by lithium in a tubular wire welding
      electrode (self-shielding flux-cored) is shown to give reductions in Cr(VI)
      concentrations and fume formation rates. Previous work has also demonstrated that
      use of a tubular wire (metal cored) containing 1% zinc can, under certain
      conditions, result in a reduction in Cr(VI) formation rate and in ozone
      concentration near the arc but with a rise in the total fume formation rate. The
      effects of different shield gases and different levels of zinc are examined. An
      experimental chromium-containing tubular wire with 1% zinc was used with the
      following shield gases: argon, Argoshield 5, Argoshield 20, Helishield 101, Ar +
      2% CO2, Ar + 5% CO2, Ar + 1% O2 and Ar + 2% O2. The wire gave > 98% reduction in
      Cr(VI) formation rate compared to the control wire provided the shield gas
      contained no oxygen. When the shield gas did contain oxygen, 1% zinc enhanced
      Cr(VI) formation rate, resulting in more than double the rates measured when
      welding with the control wire. Experiments with zinc concentrations, from 0.018
      to 0.9% using Helishield 101, gave results indicating that there is an optimum
      zinc concentration from the point of view of Cr(VI) reduction. Implications of
      the use of lithium or zinc on the overall exposure risk are discussed.

PMID- 12005131
TI  - Control of exposure to hexavalent chromium and ozone in gas metal arc welding of
      stainless steels by use of a secondary shield gas.
AB  - Previous work has demonstrated that the shield gas composition in gas metal arc
      welding can have a considerable effect on hexavalent chromium [Cr(VI)]
      concentration in the fume and on ozone concentrations near the arc. Normally a
      single shield gas is used. This paper describes a double shroud torch that allows
      used of concentric shield gases of different compositions. A solid stainless
      steel wire was used for welding. The double shroud torch used secondary shield
      gases containing small amounts of the reducing agents NO and C2H4. The Cr(VI)
      concentration in the fume and ozone concentration at a fixed point relative to
      the arc were measured and compared with results when using a single shield gas.
      Use of the reducing agents in secondary shielding using the double shroud torch
      was found to offer advantages for ozone concentration reduction compared with use
      in a conventional torch, but this was not found to be an advantage for reducing
      Cr(VI) concentrations.

PMID- 12005132
TI  - Performance of power assisted respirators during simulated asbestos removal.
AB  - Protection factors were measured on full face mask power assisted respirators
      when worn by experienced asbestos removal operatives under simulated asbestos
      removal work conditions. The sulfur hexafluoride test method as defined in
      European Standards was employed to determine the leakage into the respirators.
      Protection factors were measured on a total of 21 test volunteers. The test
      method allowed protection factors to be related to wearer activities and
      practices. Poor fitting techniques and simulated reduction in the respirator's
      performance resulted in a reduction in the protection factor. Visual inspection
      of the RPE usually worn by the volunteers identified inadequate maintenance. This
      study re-emphasises that careful selection, facepiece fit testing and correct use
      and maintenance of RPE are essential to ensure optimum protection to the wearer.

PMID- 12005133
TI  - The combination of effects on lung cancer of cigarette smoking and exposure in
      quebec chrysotile miners and millers.
AB  - Although it is well known that both cigarette smoke and microscopic airborne
      asbestos fibres can cause lung cancer, evidence as to how these two agents
      combine is nebulous. Many workers have believed in the multiplicative theory,
      whereby asbestos increases the risk in proportion to the risk from other causes.
      However, evidence against this theory is mounting: a recent review concluded that
      the multiplicative hypothesis was untenable, and that the relative risk of lung
      cancer from asbestos exposure was about twice as high in non-smokers as in
      smokers, a finding largely independent of type of asbestos fibre. The criteria
      for entry to the current study were met by 7279 men in the 1891-1920 birth cohort
      of Quebec chrysotile miners and millers. The data consisted of date of birth,
      place of employment, smoking habit, asbestos exposure accumulated to age 55 and,
      for those 5527 who died between 1950 and June 1992, date and cause of death; 533
      of the deaths were from lung cancer. For the principal analyses, ex-smokers were
      excluded from the study cohort, which comprised 5888 men, of whom 473 died of
      lung cancer. The conventional form of analysis is simply of the double dichotomy:
      non-smokers of cigarettes, 'unexposed' and exposed; all others, 'unexposed' and
      exposed. The respective standardized lung cancer mortality ratios (SMRs) were
      0.29 and 0.62; and 1.37 and 1.72. Thus, the differences in relative risk, due to
      exposure, were closely similar, 0.33 and 0.35. On the other hand, the effects of
      asbestos measured by the corresponding ratios, 2.12 and 1.25, did differ, being
      1.7 times as high in non-smokers as in others. The principal analysis was much
      more penetrating: the method was to fit models to a 'disaggregated' 6 x 10 array,
      by smoking habit (excluding ex-smokers) and asbestos exposure, of lung cancer
      SMRs. Both linear and log-linear models were fitted: the former included the
      additive and linear-multiplicative; the latter embraced the more conventional
      multiplicative form. The additive model fitted much the best. The fit of each
      multiplicative model was improved by the introduction of an interaction term that
      implied a less than multiplicative relationship. Thus smoking and exposure to
      chrysotile appear to have acted independently in causing lung cancer, with 10
      cigarettes a day having an effect roughly equivalent to exposure amounting to 700
      million particles per cubic foot x years. The refutation of the multiplicative
      hypothesis in these data reinforces its inapplicability in general; but the
      additive hypothesis is not generally applicable either. Indeed, there seems to be
      no good reason to believe that interactions conform to any simple theory. The
      implications are important.

PMID- 12005134
TI  - Reduction of exposure to laboratory animal allergens in a research laboratory.
AB  - OBJECTIVES: The purpose of this study was to determine exposure levels in the
      laboratory during different tasks and evaluate the effectiveness of safety
      equipment used to reduce personal exposure. METHODS: Personal and stationary air
      samples were collected during different tasks in a laboratory animal facility in
      which several allergen reduction strategies had been implemented. Mouse urinary
      allergen concentrations were measured using a polyclonal sandwich enzyme-linked
      immunosorbent assay. Sera from the personnel (n = 29) were analysed every 6
      months for the presence of specific antibodies against mouse and rat urinary
      allergens, and the staff answered questionnaires on work-related symptoms,
      exposure and use of respiratory protection. RESULTS: The highest airborne mouse
      allergen levels were measured during manual emptying of cages, during changing of
      cages on an unventilated table and during handling of male animals on an
      unventilated table. Automatic emptying and cleaning of cages resulted in low
      airborne allergen levels in the working room. Using a ventilated cage-changing
      wagon reduced the allergen exposure level from 77 to 17 ng/m3. The housing of
      animals in ventilated cabinets, with air exhausted through the cabinet,
      effectively prevented the release of allergens into the ambient air. The handling
      of animals on ventilated benches and the use of a centralized vacuum cleaner
      resulted in a low exposure level. Only two subjects developed specific
      immunoglobulin E of > 0.35 kU/l, of whom one was reduced to negative after
      increased use of respiratory protection. CONCLUSIONS: Effective reduction of
      exposure to allergens can be achieved by several strategies, which together
      appear to minimize sensitization to rodents.

PMID- 12005135
TI  - Application of mixed-effects models for exposure assessment.
AB  - The benefits of using linear mixed-effects models for occupational exposure
      assessment were studied by re-analysing three data sets from two published
      surveys with repeated exposure measurements. The relative contributions of
      particular characteristics affecting exposure levels were assessed as in a
      multiple regression model, while controlling for the correlation between repeated
      measurements. While one-way ANOVA allows one only to estimate unconditioned
      variance components, a mixed model enables estimation of between- and within
      worker variance components of exposure levels while accounting for the fixed
      effects of work characteristics. Consequently, we can identify the work
      characteristics affecting each variance component. Mixed models were applied to
      the data sets with repeated measurements and auxil iary information on work
      characteristics. The between-worker variance components were reduced by 35, 66
      and 80%, respectively, in the three data sets when work characteristics were
      taken into account. The within-worker (day-to-day) variability was reduced only
      in the pig farmer data set, by 25%, when accounting for work activities. In
      addition, coefficients of work characteristics from the mixed model were compared
      with coefficients resulting from originally published multiple linear regression
      models. In the rubber manufacturing data, the coefficients of the mixed model
      showed similar relative importance, but were generally smaller than the
      coefficients from regression models. However, in the pig farm data, only the
      coefficients of work activities were somewhat reduced. The mixed model is a
      helpful tool for estimating factors affecting exposure and suitable variance
      components. Identifying the factors in the working environment that affect the
      between-worker variability facilitates a posteriori grouping of workers into more
      uniformly exposed groups. Identifying the factors that affect the within-worker
      variance is helpful for hazard control and in designing efficient sampling
      schemes with reference to time schedule.

PMID- 12005136
TI  - Bitumen, polycyclic aromatic hydrocarbons and vehicle exhaust: exposure levels
      and controls among Norwegian asphalt workers.
AB  - OBJECTIVES: To characterize exposures of asphalt workers in Norway and to
      evaluate exposure control measures. METHODS: Representative asphalt paving and
      mixing operations were monitored in Norway in 1991-92 for exposures to bitumen
      fume, organic vapor, polycyclic aromatic hydrocarbons (PAHs) and vehicle exhaust
      (NO2, CO). Linear regression was used to evaluate introduced control measures.
      RESULTS: A total of 320 samples of airborne organic matter were gathered (279
      from paving). Median personal bitumen fume measurements ranged from 0.03 to 0.15
      mg/m3 and were similar in paving and asphalt mixing. According to principal
      component analysis, there were three independent sets of PAHs: (i) PAHs lighter
      than 228 g/mol; (ii) 4- to 6-ring PAHs non-detectable in 80-90% of samples; and
      (iii) naphthalene. Some NO2 (1/49) and CO (12/58) concentrations near paving
      equipment exceeded 15 min exposure limits, 2 and 25 p.p.m., respectively.
      Changing sampling methods midway through the study had a significant impact on
      the measured bitumen fume and organic vapor levels. For pavers, lower application
      temperatures reduced organic vapor, but not bitumen fume, exposures. Retrofitting
      a paving machine produced at least a 5-fold reduction in exposure to airborne
      organic matter. Work in tunnels increased PAH exposures, but general ventilation
      partially counteracted this effect. CONCLUSIONS: The observed exposure levels
      indicate that some potentially hazardous exposures may have occurred during
      paving in Norway. Bitumen fume, organic vapor and PAH exposures can be reduced
      using appropriate engineering control measures.

PMID- 12005137
TI  - Generation of controlled atmospheres for the determination of the irritant
      potency of peroxyacetic acid.
AB  - Given the physical properties of peroxyacetic acid, which decomposes into acetic
      acid and hydrogen peroxide, the generation and analysis of controlled atmospheres
      used to test the irritant potency of this peracid in mice require specific
      developments. The sampling and analytical method was based on the simultaneous
      sampling on a titanyl sulphate-impregnated silica gel tube (allowing the
      determination of total peroxides, peroxyacetic acid and hydrogen peroxide) and in
      an impinger containing a methyl-p-tolyl sulphide solution (of which the analysis
      yields the concentration of total acids, peroxyacetic acid and acetic acid, and
      peroxyacetic alone). From these results the concentrations of the different
      products can be inferred without interference. A special device composed of inert
      materials was designed for the generation of the controlled atmosphere. Buffering
      the peroxyacetic solution at pH 7 with a phosphate buffer allowed the generation
      of peroxyacetic acid atmospheres with negligible concentrations of acetic acid
      and hydrogen peroxide.

PMID- 12005138
TI  - Sensory irritation of acetic acid, hydrogen peroxide, peroxyacetic acid and their
      mixture in mice.
AB  - The expiratory bradypnoea indicative of upper airway irritation in mice was
      evaluated during a period of 60 min of oronasal exposure to acetic acid, hydrogen
      peroxide and peroxyacetic acid vapours. The airborne concentration resulting in a
      50% decrease in the respiratory rate of mice (RD50) was calculated for each
      chemical. The concentration-response curves of acetic acid, hydrogen peroxide and
      peroxyacetic acid had similar slopes. The results did however show that the three
      chemicals had different irritant potencies. The RD50 values of acetic acid,
      hydrogen peroxide and peroxyacetic acid were 227, 113 and 5.4 p.p.m.
      respectively. Moreover, a mixture containing 53% acetic acid, 11% hydrogen
      peroxide and 36% peroxyacetic acid had an RD50 of 10.6 ppm, 3.8 ppm being
      peroxyacetic acid, which is 1.4 times lower than the theoretical value estimated
      from the fractional concentrations and the respective RD50s of the individual
      components. On the basis of a TLV-STEL (threshold limit value for short-term
      exposure limit) equal to 0.1 RD50, the TLV-STELs for acetic acid, hydrogen
      peroxide and peroxyacetic acid should not exceed 20, 10 and 0.5 p.p.m.
      respectively. On the basis of a TLV-TWA (time-weighted average) equal to 0.03
      RD50, the TLV-TWAs for these same chemicals should not exceed 5, 3 and 0.2 p.p.m.
      respectively. Finally, these values and existing TLVs in Europe and the USA are
      compared.

PMID- 12005139
TI  - Infectious risks for oral implants: a review of the literature.
AB  - The use of oral implants in the rehabilitation of partially and fully edentulous
      patients is widely accepted even though failures do occur. The chance for
      implants to integrate can for example be jeopardised by the intra-oral presence
      of bacteria and concomitant inflammatory reactions. The longevity of
      osseointegrated implants can be compromised by occlusal overload and/or plaque
      induced peri-implantitis, depending on the implant geometry and surface
      characteristics. Animal studies, cross-sectional and longitudinal observations in
      man, as well as association studies indicate that peri-implantitis is
      characterised by a microbiota comparable to that of periodontitis (high
      proportion of anaerobic Gram-negative rods, motile organisms and spirochetes),
      but this does not necessarily prove a causal relationship. However, in order to
      prevent such a bacterial shift, the following measures can be considered:
      periodontal health in the remaining dentition (to prevent bacterial
      translocation), the avoidance of deepened peri-implant pockets, and the use of a
      relatively smooth abutment and implant surface. Finally, periodontitis enhancing
      factors such as smoking and poor oral hygiene also increase the risk for peri
      implantitis. Whether the susceptibility for periodontitis is related to that for
      peri-implantitis may vary according to the implant type and especially its
      surface topography.

PMID- 12005140
TI  - Clinical results of alveolar ridge augmentation with mandibular block bone grafts
      in partially edentulous patients prior to implant placement.
AB  - A group of 15 partially edentulous patients who needed alveolar ridge
      augmentation for implant placement, were consecutively treated using a two-stage
      technique in an outpatient environment. A total of 18 alveolar segments were
      grafted. During the first operation bone blocks harvested from the mandibular
      ramus or symphysis were placed as lateral or vertical onlay grafts and fixed with
      titanium osteosynthesis screws after exposure of the deficient alveolar ridge.
      After 6 months of healing the flap was re-opened, the screws were removed and the
      implants placed. Twelve months after the first operation implant-supported fixed
      bridges could be provided to the patients. Mean lateral augmentation obtained at
      the time of bone grafting was 6.5 +/- 0.33 mm, that reduced during healing
      because of graft resorption to a mean of 5.0 +/- 0.23 mm. Mean vertical
      augmentation obtained in the 9 sites where it was needed was 3.4 +/- 0.66 mm at
      bone grafting and 2.2 +/- 0.66 mm at implant placement. Mean lateral and vertical
      augmentation decreased by 23.5% and 42%, respectively, during bone graft healing
      (before implant insertion). Mandibular sites showed a larger amount of bone graft
      resorption than maxillary sites. All the 40 implants placed were integrated at
      the abutment connection and after prosthetic loading (mean follow-up was 12
      months). No major complications were recorded at donor or recipient sites. Soft
      tissue healing was uneventful, and pain and swelling were comparable to usual
      dentoalveolar procedures. A visible ecchymosis was present for 4 to 7 days when
      the bone was harvested from the mandibular symphysis. From a clinical point of
      view this procedure appears to be simple, safe and effective for treating
      localised alveolar ridge defects in partially edentulous patients.

PMID- 12005141
TI  - The effects of an immediately pre-surgical chlorhexidine oral rinse on the
      bacterial contaminants of bone debris collected during dental implant surgery.
AB  - Dental implant surgery produces bone debris that can be used in the "simultaneous
      augmentation" technique. Although this debris is contaminated with oral bacteria,
      a stringent aspiration protocol has been shown to reduce the levels of
      contamination. Chlorhexidine mouthrinse is a well-proven antibacterial rinse that
      has been shown to reduce infectious complications associated with dental
      implants. This study examined the effect of pre-operative rinsing with a 0.1%
      chlorhexidine digluconate mouthrinse on the bacterial contaminants present in
      collected bone debris bone (CBD). Twenty partially edentate patients were
      randomly allocated into equal groups and underwent bone collection using the
      Frios Bone Collector (FBC) during the insertion of two dental implants. In group
      T a pre-operative chlorhexidine rinse was used, whilst in group C sterile water
      was used. For both groups, a stringent bone collection protocol was used. Bone
      samples were immediately transported for microbial analysis. Colonial and
      microscopic morphology, gaseous requirements and identification kits were
      utilised for identification of the isolated microbes. Thirty-nine species were
      identified including a number associated with disease, in particular Actinomyces
      odontolyticus, Clostridium bifermentans, Prevotella intermedia, and
      Propionibacterium propionicum. Samples from group T (chlorhexidine mouthrinse)
      yielded significantly fewer organisms (P < 0.001) than in group C (sterile water
      mouthrinse). Gram-positive cocci dominated the isolates from both groups. It is
      concluded that if bone debris is to be used for the purpose of immediate
      simultaneous augmentation, a preoperative chlorhexidine mouthrinse should be
      utilised in conjunction with a stringent aspiration protocol to reduce further
      the bacterial contamination of CBD.

PMID- 12005142
TI  - Marginal bone reaction to oral implants: a prospective comparative study of Astra
      Tech and Branemark System implants.
AB  - In earlier studies of Astra Tech and Branemark System implants, high survival
      rates and small marginal bone changes have been demonstrated. The aim of this
      study was to compare the two systems, primarily with regard to marginal bone
      changes, but also with regard to other clinical variables of interest. The
      present paper describes the results after three years. Sixty-six patients were
      included in the study and randomly assigned to treatment with Astra Tech implants
      (n = 184) or Branemark System implants (n=187). The marginal bone level was
      radiographically examined at fixture insertion, at abutment connection, at
      baseline (delivery of the prosthetic construction) and at 1- and 3-year follow-up
      examinations. Between fixture insertion and the baseline examination, the pattern
      of marginal bone resorption differed between the two systems. However, there was
      no significant marginal bone change between baseline and the 1-year examination
      or between the 1- and 3-year examinations. Nor were there any differences between
      the systems. The mean bone loss in the upper jaw between BL (baseline) and 3
      years was 0.2 +/- 0.3 mm for Astra Tech implants and 0.2 +/- 0.1 mm for Branemark
      System implants. The corresponding figures for the lower jaw were 0.3 +/- 0.2 mm
      and 0.2 +/- 0.1 mm. The survival rate of Astra Tech implants was significantly
      higher (98.9%) than for Branemark System implants (95.2%). However, five of the
      nine implant losses in the Branemark group occurred in one patient. For that
      reason, this result must be interpreted with caution. The number of patients with
      implant losses did not differ significantly between the systems. Few
      complications were recorded up to 3 years.

PMID- 12005143
TI  - A long-term follow-up of 76 Branemark single-tooth implants.
AB  - In a previous study (Haas et al. 1995), we reported on preliminary results of 76
      Branemark implants placed in 71 patients with single-tooth gaps. The present
      study examines the results of the same group over a longer period of time: 55
      implants were followed for more than 5 years, 12 for a period between 4 and 5
      years and 1 implant for 46 months. One patient died 3 years after implant
      placement. Five patients lost their implant within 24 months after insertion. The
      drop-out rate was 2 implants in 2 patients. The recall rate was thus 97%. Of the
      5 implant failures, 2 were located in the maxilla and 3 in the mandible. The
      Kaplan-Meier survival probability was 93% after 120 months. 74% of the sites
      showed healthy peri-implant soft tissue conditions. At 15 implants (22%) a bone
      resorption of more than 2 mm was observed on intraoral radiographs. The mean bone
      resorption was 1.8 mm in the maxilla and 1.3 mm in the mandible and did not
      increase with time (Pearson correlation coefficient: r = -0.06, P = 0.59).
      Abutment loosening occurred in 7 implants (10%), however all abutments that were
      fixed with a defined torque subsequently remained stable. Thus the favourable
      preliminary results could be maintained over an average 66 months, indicating
      that if implant loss happens it seems to occur during the first 2 years after
      insertion.

PMID- 12005144
TI  - Treatment of severe atrophy of the maxilla with the prefabricated free
      vascularized fibula flap.
AB  - Treatment of severe maxillary atrophy despite complex major surgery often ends up
      with an unsatisfactory result. This paper presents the augmentation of the
      maxilla with a prefabricated free vascularized fibula flap in combination with
      ITI implants (Straumann AG, Waldenburg, Switzerland) in 4 patients. The technique
      of prefabrication for the reconstruction of maxillofacial defects is described
      based on the experience with 17 patients. The key points of this treatment are i)
      preoperative planning and fabrication of the drilling template; ii)
      prefabrication of the fibula with ITI implants and performing of a
      'vestibuloplasty" using a skin graft; iii) technical construction and fabrication
      of the suprastructure and the denture; iv) reconstruction of the maxilla using
      the prefabricated fibula as free vascularized flap. The reconstructions with the
      fibula flaps were successful and the 18 ITI implants that have been inserted
      showed good osseointegration without loss of attachment in all 4 patients after a
      mean observation period of 12 months.

PMID- 12005145
TI  - Particulate Bioglass reduces the viability of bacterial biofilms formed on its
      surface in an in vitro model.
AB  - 45S5 Bioglass is a bioactive implant material which, in its particulate form, is
      used in the repair of periodontal defects. The surface reactions undergone by
      this material in an aqueous environment may exert an antibacterial effect that
      would be beneficial to periodontal surgical treatment. Biofilms of Streptococcus
      sanguis, an early plaque former, and mixed species biofilms from a salivary
      inoculum grown under conditions similar to those associated with periodontal
      implants, were grown on particulate Bioglass in a constant depth film fermenter
      (CDFF). Control biofilms were grown on inert glass particulates. At sample times
      of 3, 24 and 48 hours the viability of biofilms of S. sanguis grown on Bioglass
      was significantly lower than for those grown on inert glass. In the experiments
      with subgingivally-modelled mixed species biofilms, the total anaerobic counts
      were significantly lower on Bioglass after 24 and 48 hours, but not 96 or 168
      hours, compared to inert glass. Thus, particulate Bioglass has the potential to
      reduce bacterial colonisation of its surface in vivo, a feature relevant to post
      surgical periodontal wound healing.

PMID- 12005146
TI  - Evaluation of accuracy of computer-aided intraoperative positioning of endosseous
      oral implants in the edentulous mandible.
AB  - The overall accuracy of a novel surgical computer-aided navigation system for
      placement of endosseous implants was evaluated. Five dry cadaver mandibles were
      scanned using high resolution computed tomography (HRCT). The position of four
      interforaminal dental implants was planned on the computer screen and transferred
      to the cadaver mandibles using VISIT, a surgical navigation software developed at
      the Vienna General Hospital. The specimens were HRCT-scanned again to compare the
      position of the implants with the preoperative plan on reformatted slices after
      matching of the pre- and postoperative data sets using the mutual information
      technique. The overall accuracy was 0.96 +/- 0.72 mm (range 0.0-3.5 mm). No
      perforation of the mandibular cortex or damage to the mandibular canal occurred.
      We conclude that computer-aided implant surgery can reach a level of accuracy
      where further clinical developments are feasible.

PMID- 12005147
TI  - Resonance frequency assessment of dental implant stability with various bone
      qualities: a numerical approach.
AB  - Resonance frequency analysis (RFA) has been used by several investigators to
      assess the boundary conditions of dental implants. The goal of the current study
      was to determine the vibrating behavior of a dental implant under various
      surrounding bone conditions. A 3D finite element (FE) model of a cylinder-type
      titanium implant was developed. In this model, the implant was embedded into a
      cubic section of bone. The model was first validated using a series of modal
      testing experiments. The effects of bony conditions on the resonance frequencies
      of the implant were computed with different bone types and bone densities. Our
      results show that the resonance frequency of the implant with type III
      surrounding bone decreased linearly (r = -0.996, P < 0.01) from 17.9 kHz (without
      loss in bone density) to 0.6 kHz (90% loss in bone density) when the bone
      densities were decreased. On the other hand, without bone loss, the highest
      resonance frequency value (36.1 kHz) was found when the implant was placed into
      type I surrounding bone. In contrast, the resonance frequency of the implant with
      type IV bone quality was found to be 9.9 kHz, which is almost four-fold less than
      that found in the type I model. These results suggest that RFA could serve as a
      non-invasive diagnostic tool for detecting the stability of dental implants
      during the healing stages and in subsequent routine follow-up care after
      treatment.

PMID- 12005148
TI  - Evaluation of stability of titanium and hydroxyapatite-coated osseointegrated
      dental implants: a pilot study.
AB  - An endosseous implant is described as osseointegrated when it is immobile in
      function. Objective measures of stability testing have been described. The
      Periotest is a commercially available device that is used for this purpose. This
      study was designed to measure stability of endosseous implants placed in the
      mandible. Implants were placed in the mandibular canine or first premolar area to
      support an overdenture prosthesis. Stability was evaluated through the use of a
      Periotest device at the time of implant placement and following one year of
      functional loading. Implant designs were either a screw-shaped titanium alloy or
      a hydroxyapatite-coated cylinder. A total of 54 implants were placed, 37 were
      titanium screw-shaped implants, while the remaining 17 were hydroxyapatite
      cylinders. Initial measurements of stability showed no difference due to implant
      type. Following one year of functional loading, titanium screw-shaped implants
      were more stable than hydroxyapatite implants (P < 0.05). The difference in
      implant rigidity following a period of functional loading may be an indication of
      a difference in osseointegration between the two implants used in this study.

PMID- 12005149
TI  - Expression of bone morphogenetic protein in the course of osteoinduction by
      recombinant human bone morphogenetic protein-2.
AB  - To clarify the mechanism of osteoinduction by recombinant human bone
      morphogenetic protein-2 (rhBMP-2), we examined the time-course localization of
      bone morphogenetic proteins (BMPs) immunostained by an anti-BMP-2 monoclonal
      antibody after implantation of pellets consisting of rhBMP-2 and collagen in rat
      calf muscle pouch. On day 3 after implantation, BMP was detected in the entire
      lump, and the intensity of staining for BMP around the implant on day 7 was
      weaker than that on day 3. The staining for BMP decreased with time and the
      region of staining for BMP remained more centralized in the implant. On day 10
      after implantation, BMP was observed in part of the newly induced cartilage,
      especially around chondrocytes. On day 14 after implantation, BMP was localized
      in the newly induced woven bone. On day 21, BMP staining was found in osteoblasts
      at the surface of the newly induced bone. Especially, the staining for BMP
      decreased from day 10 to day 21. These results indicate that the woven bone was
      replaced with mature lamellar bone from day 14 to day 21. The present findings
      suggest that rhBMP-2 plays an important role in osteoinduction, especially at the
      early stage.

PMID- 12005150
TI  - The effect of titanium surface roughness on the adhesion of monocytes and their
      secretion of TNF-alpha and PGE2.
AB  - Dental implant surfaces are important in determining the tissue/surface
      interaction. One of the first cells to adhere to the implant surface is the
      monocyte. This study examines the effect of surface roughness on monocyte
      adhesion and cytokine secretion. Monocyte adherence to titanium discs of 4
      different degrees of surface roughness and plastic surfaces was assayed. Blood
      mononuclear cells were incubated for 1.5 h in 16 mm culture wells into which
      titanium discs had been placed. Non-adherent cells were washed off and the
      numbers of remaining adherent monocyte determined by DNA quantification. TNF
      alpha and PGE2 secretion in media from overnight cultures of attached monocytes
      stimulated with lipopolysaccharide (LPS) was quantified using ELISA and RIA,
      respectively. Monocyte adherence to rough titanium surfaces was greater than to
      turned titanium surfaces, while the lowest adherence was to the plastic surface.
      No significant differences in adherence to 250, 75 or 25 microm blasted surfaces
      could be detected. The number of adherent monocytes increased with time, with
      maximum adhesion after 2 h of incubation. Incubation of monocytes adherent to
      titanium surfaces resulted in a decrease of less than 30% in their numbers over 7
      days, whereas cells attached to plastic surfaces decreased to non-detectable
      numbers after 48 h. Porphyromonas gingivalis LPS stimulation upregulated TNF
      alpha and PGE2 secretion into the media. The LPS-induced TNF-alpha and PGE2
      secretion was independent of the titanium surface roughness, however the lowest
      amounts of TNF-alpha and PGE2 were secreted from cells attached to plastic
      surfaces. The results of this study indicate that the number of monocytes
      attached to blasted titanium surfaces is significantly greater than to machined
      titanium surfaces. PGE2 and TNF-alpha secretion is less influenced by titanium
      surface roughness.

PMID- 12005151
TI  - Bone formation in transforming growth factor beta-I-loaded titanium fiber mesh
      implants.
AB  - The osteoconductive properties of porous titanium (Ti) fiber mesh with or without
      a calcium phosphate (Ca-P) coating and osteoinductive properties of noncoated Ti
      fiber mesh loaded with recombinant human Transforming Growth Factor beta-1 (rhTGF
      beta1) were investigated in a rabbit non-critical size cranial defect model. Nine
      Ca-P-coated and 18 non-coated porous titanium implants, half of them loaded with
      rhTGF-beta1, were bilaterally placed in the cranium of 18 New Zealand White
      rabbits. At 8 weeks postoperative, the rabbits were sacrificed and the skulls
      with the implants were retrieved. Histological analysis demonstrated that in the
      TGF-beta1-loaded implants, bone had been formed throughout the implant, up to its
      center, whereas in the non-loaded implants only partial ingrowth of bone was
      observed. Bone formation had a trabecular appearance together with bone marrow
      like tissue. No difference in ingrowth could be observed between the non-TGF
      beta1-loaded non-coated implants and the Ca-P-coated ones. All histological
      findings were confirmed by image analysis: 97% ingrowth was seen in the rhTGF
      beta1-loaded implants, while only 57% and 54% ingrowth was observed in the non
      loaded Ca-P-coated and non-coated implants, respectively. Bone surface area and
      bone fill were significantly higher in the rhTGF-beta1-loaded implants (1.37 mm2
      and 36%, respectively) than in the non-loaded implants (0.57 mm2 and 26%). No
      statistical difference was found for any parameter between the Ca-P-coated and
      noncoated implants. Quadruple fluorochrome labeling showed that in the Ti and Ti
      CaP implants mainly bone guidance had occurred from the former defect edge, while
      in the Ti-TGF-beta1 implants bone formation had mainly started in the center of a
      pore and proceeded in a centrifugal manner. Our results show that: (1) the
      combination of Timesh with TGF-beta1 can induce orthotopic bone formation; (2) Ti
      fiber mesh has good osteoconductive properties; (3) a thin Ca-P coating, as
      applied in this study, does not seem to further enhance the bone-conducting
      properties of a titanium scaffold material.

PMID- 12005152
TI  - Changes in kinetics of cerebral auto-regulation with head-down bed rest.
AB  - Thoraco-cephalic fluid shift induced by weightlessness may influence cerebral
      autoregulation. Our objective was to assess effects of simulated weightlessness
      by a 7-day head-down bed rest (HDBR) on the kinetics of cerebral blood flow (CBF)
      autoregulation in eight healthy women (27.9 +/- 0.9 years). This was studied by
      transcranial Doppler (TCD) of the middle cerebral artery (MCA) during the sudden
      decrease in blood pressure (BP) induced by quickly deflating thigh cuff aftera 4
      min arterial occlusion before (D - 3), during (D2, D5) and after the HDBR (D +
      1). BP (Finapres) and MCA maximal blood flow velocity were continuously recorded.
      Cerebrovascular resistance (CR) was expressed as the ratio of mean BP to mean MCA
      velocity. The CR slope was defined as changes in CR per second during the BP
      decrease. The magnitude of the relative decrease in mean BP and MCA velocity as
      well as the CR slope did not differ significantly before, during and after the
      HDBR, showing no major impairment of cerebral autoregulation during short-term
      HDBR. The time to maximum decrease in CR (T1 in s), corresponding to the maximum
      vasodilation was reduced on D2 (7-2 +/- 0.6) versus D - 3 (9.9 +/- 1-3), D5 (9-6
      +/- 0.8) and R + 1 (11.7 +/- 11) probably as a result of the fluid shift. We also
      looked if the responses during the thigh cuff release differed in women according
      to their tolerance to the 10 min stand test performed after the HDBR: T1 was
      larger in the five women who presented orthostatic intolerance suggesting that
      some differences in cerebral autoregulatory responses may be related to
      orthostatic intolerance.

PMID- 12005153
TI  - Effects of exercise training on aerobic and functional capacity of end-stage
      renal disease patients.
AB  - The aim was to assess the effects of exercise training on aerobic and fuctional
      capacity of patients with end-stage renal disease (ESRD). Patients completed an
      incremental exercise test on a cycle ergometer to determine VO2 peak and VO2 at
      ventilatory threshold (VT; V-slope). On a separate day they performed two
      constant load exercise tests on a cycle ergometer at 90% of VT and at a workload
      of 33 W, to determine VO2 kinetics. Functional capacity was assessed using
      measurements of sit-to-stands (STS-5, STS-60) and a walk test. Dialysis patients
      were randomly allocated to an exercise (ET: n = 18, age = 57.3 years) or control
      (C: n = 15, age = 50.5 - 5 years) group. The ET group participated in an exercise
      training programme involving cycling for 3 months. Repeated measures ANOVA
      revealed significant time by group interactions (P < 0.05) following training for
      VO2 peak (ET: 17 +/- 6.1 versus 19.9 +/- 6-3, C: 19.5 +/- 4.7 versus 188 +/- 4.9
      ml kg min(-1)) and VO2-VT (ET: 10.7 +/- 3.5 versus 11.8 +/- 3.3, C:12.9 +/- 3.2
      versus 119 +/- 3.5 ml kg min(-10). VO2 kinetics remained unchanged in both groups
      at 90% -VT, but a trend (P = 0.059) towards faster kinetics at the 33 W was
      observed (ET: 49.6 +/- 19.5 versus 37.8 +/- 12.7, C: 42.8 +/- 13 versus 49.4 +/-
      20.2 s). Significant time by group interactions (P < 0.05) were also observed for
      STS-5 (ET: 14.7 +/- 6.2 versus 11.0 +/- 3.3, C: 12.8 +/- 4.4 versus 12.7 +/- 4.8
      s) and STS-60 measurements (ET: 21.2 + 7.2 versus 26.9 +/- 6.2, C: 23.7 +/- 6.8
      versus 24.1 +/- 7.2). Three months of exercise rehabilitation significantly
      improves peak exercise capacity of patients with ESRD. Measurements of VO2
      kinetics and functional capacity suggest that longer time might be needed to
      induce peripheral adaptations.

PMID- 12005154
TI  - Can blood pressure responses to tests unmask future blood pressure trends and the
      need for antihypertensive medication? Ten years of follow-up.
AB  - An exaggerated blood pressure (BP) response to test may unmask the subjects who
      have a high risk of developing hypertension. In this prospective 10 years of
      follow-up, we examined whether the predictive value of casual BP measurements on
      future BP level and need for antihypertensive medication could be improved by
      using BP responses to different physical tests. At baseline, BP was recorded by
      casual measurements and intra-arterial monitoring. During the intra-arterial BP
      recording, standardized postural and exercise tests were performed on 97 healthy,
      untreated men (34 normotensive, 29 borderline hypertensive, and 34 mild
      hypertensive). After 10 years of follow-up, 87 of them (90%) returned for casual
      and non-invasive 24-h BP measurements. At follow-up, 20 (23%) of the men had
      antihypertensive medication. The prediction of casual systolic blood pressure
      (SBP) was best improved by SBP at 10 min after the dynamic exercise test (adj. R2
      = 0.448; adj. R2 = 0.356 for casual SBP alone). The prediction of casual
      diastolic blood pressure (DBP) was most improved by DBP at 10 min after the
      dynamic exercise test (adj. R2 = 0.282; adj. R = 0.259 for casual BP alone). SBP
      in the supine test best improved the prediction of 24-h SBP (adj. R2 = 0 448;
      adj. R2 = 0.275 for casual SBP alone). DBP in the standing test best improved the
      prediction of 24-h DBP (adj. R2 = 0.252; adj. R2 = 0.214 for casual DBP alone).
      Pre-exercise DBP and casual SBP were the best predictors of the need for
      antihypertensive medication (Cox-Snell R2 = 0.256; Cox-Snell R2 = 0.164 for
      casual SBP alone). In conclusion the prediction of future BP and need for
      antihypertensive medication can be improved by using BP measurements during
      postural and exercise tests. Future SBP is more predictable than DBP.

PMID- 12005155
TI  - Effect of flow and vascular heterogeneity on glucose metabolism in isolated dog
      hearts.
AB  - In non-ischaemic myocardium glucose uptake is assumed to be proportional to blood
      flow. We investigated the effect of regional vascular heterogeneity on glucose
      metabolism at various flow rates in the isolated blood-perfused dog hearts.
      Aortic bolus injections contained an intravascular reference tracer (albumin) and
      two of three glucoses: L-glucose (an extracellular tracer), D-glucose and 2-deoxy
      D-glucose. Flow ranged from 0.5 to 2 4 ml min(-1) g(-1). Vascular heterogeneity
      was calculated from the albumin outflow dilution curve. A three-region convection
      diffusion from the abumin outflow dilution curve. A three-region, convection
      diffusion model was fitted to outflow dilution curves to estimate glucose
      metabolic rate (consumption). The results of 2-deoxy-D-glucose experiments showed
      that the lumped constant was dependent on flow, glucose metabolic rate was
      proportional to flow and dependent on the heterogeneity of the myocardial
      vasculature. The results support the views that without accounting the regional
      flow heterogeneity, glucose metabolic rate will be underestimated.

PMID- 12005156
TI  - Effects of dexamethasone on the metabolic responses to mental stress in humans.
AB  - The haemodynamic effects of the sympathetic nervous system (SNS) activations
      elicited by hypoglycaemia, acute alcohol administration, or insulin can be
      prevented by a pretreatment with dexamethasone in humans. This suggests a
      possible role of central corticotropin releasing hormone (GRIT) release. Mental
      stress activates the SNS, and decreases systemic vascular resistances though a
      beta-adrenergic-mediated vasodilation thought to involve vascular nitric oxide
      release. It also increases insulin-mediated glucose disposal, an effect
      presumably related to vasodilation. In order to evaluate whether activation of
      SNS by mental stress is glucocorticoid-sensitive, we monitored the haemodynamic
      and metabolic effects of mental stress during hyperinsulinaemia in healthy humans
      with and without a 2-day treatment with 8 mg day(-1) dexamethasone. Mental stress
      decreased systemic vascular resistances by 21.9% and increased insulin-mediated
      glucose disposal by 2 8.4% without dexamethasone pretreatment. After 2 days of
      dexamethasone treatment, whole body insulin-mediated glucose disposal was
      decreased by 40.8%. The haemodynainic effects of mental stress were however, not
      affected. Mental stress acutely increased insulin-mediated glucose disposal by
      28.0%. This indicates that mental stress elicits a stimulation of SNS through
      dexamethasone-insensitive pathway, distinct of those activated by insulin,
      alcohol, or hyperglycaemia.

PMID- 12005157
TI  - Effect of a vibration exposure on muscular performance and body balance.
      Randomized cross-over study.
AB  - This randomized cross-over study was designed to investigate the effects of a 4
      min vibration bout on muscle performance and body balance in young, healthy
      subjects. Sixteen volunteers (eight men, eight women, age 24-33 years) underwent
      both the 4-min vibration- and sham-interventions in a randomized order on
      different days. Six performance tests (stability platform, grip strength,
      isometric extension strength of lower extremities, tandem-walk, vertical jump and
      shuttle run) were performed 10 min before (baseline), and 2 and 60 min after the
      intervention. The effect of vibration on the surface electromyography (EMG) of
      soleus, gastrocnemius and vastus lateralis muscles was also investigated. The
      vibration-loading, based on a tilting platform, induced a transient (significant
      at the 2-min test) 2.5% net benefit in the jump height (P = 0.019), 3.2% benefit
      in the isometric extension strength of lower extremities (P=0.020) and 15.7%
      improvement in the body balance (P = 0.049). In the other 2-min or in the 60-min
      tests, there were no statistically significant differences between the vibration-
      and sham-interventions. Decreased mean power frequency in EMG of all muscles
      during the vibration indicated evolving muscle fatigue, while the root mean
      square voltage of EMG signal increased in calf muscles. We have shown in this
      study that a single bout of whole body vibration transiently improves muscle
      performance of lower extremities and body balance in young healthy adults.

PMID- 12005158
TI  - Effects of in vitro exposure of alcohol on surface receptor expression of human
      platelets.
AB  - Platelet inhibition after moderate alcohol consumption in patients with ischaemic
      heart disease may contribute to reducing the risk for developing acute coronary
      syndromes. However, the mechanism by which ethanol affects platelets is not
      clarified. We sought to determine the in vitro effects of alcohol on the surface
      expression of human platelet receptors using whole blood flow cytometry. Blood
      samples from 10 healthy volunteers were incubated for 30 min with 25 and 50 mmol
      l(-1) of phosphate buffered saline diluted grain ethanol, concentrations often
      used in in vitro studies. The surface expression of platelet receptors was
      determined by flow cytometry after fixation with 2% paraformaldehyde using the
      following monoclonal antibodies: CD 41 (GP IIb/IIIa), CD 42b (GP Ib), CD 62p (P
      selectin), CD 51/CD 61 (vitronectin receptor), CD 31 (PECAM-1), CD 107a (LAMP-1),
      CD 107b (LAMP-2), CD 63 (LIMP, LAMP-3) and CD 151 (PETA-3). Dose-dependent
      inhibition of GP IIb/IIIa, P-selectin, CD 63 and CD 107a receptor expression was
      observed in the ethanol-treated whole blood samples. This study for the first
      time establishes a direct effect of ethanol on selective major platelet
      receptors. Beneficial cardiovascular properties of moderate alcohol consumption
      may be explained by ethanol's antiplatelet action.

PMID- 12005159
TI  - Surface diaphragmatic electromyogram changes after laparotomy.
AB  - The aim of this human study was to objective cliaphragmatic electromyogram (EMG)
      changes after supraombilical laparotomy. The surface diapbragmatic FMG was
      recorded in patients (before and after laparotomy), and in healthy volunteers,
      during standardized inspiratory efforts sustained at -30 cmH2O (Muller
      manoeuvres). The quantitative EMG analysis showed significant postoperative
      modifications: the root mean square (RMS) increased and the median frequency (ME)
      decreased. These modifications are compatible with an altered diaphragmatic
      excitability and/or a reduced central drive to the diaphragm.

PMID- 12005160
TI  - Haemodynamic limitations and exercise performance in peripheral arterial disease.
AB  - It has been frequently argued that haemodynamic limitations are poor predictors
      of exercise performance in people with peripheral arterial disease (PAD) and
      intermittent claudication. This review has tried to address this argument through
      a review of published data that appears to support or counterbalance it, brief
      consideration of some of the methodological limitations associated with these
      data, as well as some other considerations. The main argument rests primarily
      upon data about the resting ankle-brachial index (ABI) and/or blood flow after
      calf exercise or an ischaemic challenge; whereas the counter argument rests
      mainly on data about blood flow during walking or cyding exercise. Consideration
      of the limitations of all methods suggests that the measurement of blood flow
      during exercise has the greatest value in explaining differences in exercise
      performance amongst claudicants; whereas the other methods are relatively limited
      in their explanatory value. This strengthens the counter argument and undermines
      the main argument proposed by others. Consequently, asserting that haemodynamic
      limitations are poor predictors of exercise performance in claudicants is not
      justified in light of available evidence.

PMID- 12005161
TI  - Cardiovascular responses during submaximal electrical stimulation-induced leg
      cycling in individuals with paraplegia.
AB  - This study investigated the cardiovascular responses during electrical
      stimulation-induced leg cycling (ES-LCE) in people with paraplegia (PARA)
      compared with voluntary leg cycling (VOL) at similar levels of oxygen uptake in
      able-bodied (AB) individuals. Six PARA with sensory and motor complete spinal
      cord lesions (TS-T9) and six AB participated in this study. Oxygen uptake (VO2),
      stroke volume (SV), heart rate (HR) and cardiac output (Q) were measured at rest
      and during submaximal, steady-state leg cycling. At the highest power output
      achieved (9.2 +/- 2.4 W for PARA versus 42.8 +/- 1.0 W for AB), VO2 was augmented
      above resting levels to 0.75 +/- 0.11 min(-1) in PARA and to 0.74 +/- 0.071 min(
      1) in AB. HR and SV were also increased during ES-LCE in PARA (92.1 +/- 8-6 beats
      min(-1) and 93.9 +/- 11.3 ml bea(-1), respectively) and during VOL in AB (83.9 +/
      9.2 beats min(-1) and 89.7 +/- 9.0 ml beat(-1), respectively). At an equivalent
      submaximal VO2, HR and SV were not different between the two groups, however, Q
      was higher in PARA (6.6 +/- 0.7 versus 4.1 +/- 0.9 1 min l(-1) deltaVO2). These
      data suggest that ES-LCE at relatively low power outputs elicits increases in
      several cardiovascular variables in PARA. Furthermore, it is possible that ES-LCE
      leads to a 'hyperkinetic circulation' (a greater Q for a given VO2).

PMID- 12005162
TI  - Lopromide one-sample clearance as a measure of glomerular filtration rate.
AB  - OBJECTIVE: The pharmacokinetics of iopromide were analysed using a two
      compartment model. The optimal point of time for blood withdrawal for calculation
      of a one-sample clearance was determined. METHODS: Plasma concentration of iodine
      was measured up to 8 h postinjection (p.i.) in 62 adult patients who received 120
      ml iopromide for computed tomography (CT). A two exponential function was fitted
      by a weighted least error square method. As reference method, clearance was
      calculated from this function and the injected amount of iodine. Empirical
      parameters for calculation of one-sample clearance were determined. This one
      sample clearance was compared with one-sample clearance calculated according to
      formulas developed for Tc99m-DTPA by Jacobsson as well as a two sample method.
      RESULTS: Total distribution volume of iopromide was calculated as 0.242 Lkg(-1)+/
      5.9%. A high correlation of all one-sample method and the two-sample method with
      reference to clearance was found. Best estimation of iopromide plasma clearance
      was achieved by determining one-sample clearance 270 or 285 min p. i. with
      SD(y.x) of 5.8 ml min(-1). CONCLUSIONS: After administration of 120 ml iopromide,
      one-sample plasma clearance can be calculated with low estimation error taking
      one blood sample at an appropriate time point. Late phase pharmacokinetics of
      iopromide found in the present study showed to be virtually identical to results
      published for iohexol and Tc99m-DTPA.

PMID- 12005163
TI  - Investigation of the charge on threading edge dislocations in GaN by electron
      holography.
AB  - We present direct evidence for the charging around end-on threading edge
      dislocations in n-type GaN doped with silicon by off-axis electron holography in
      a transmission electron microscope. It is shown that the inner potential is
      reduced by up to 2.5 V within 10 nm of the dislocation, consistent with a
      negatively charged core. The results, which can be fitted with an unscreened
      potential, are consistent with a line charge of about 2 electrons/c, where c =
      0.52 nm is the unit cell parameter of GaN. The origin of this line charge is
      discussed. The application of the method to other types of dislocation is also
      considered.

PMID- 12005164
TI  - Computer-assisted simulation of high-voltage electron microscopy using serial
      images recorded by conventional transmission electron microscopy.
AB  - Here we describe a computer-assisted method which, based on conventional
      transmission electron microscopy, renders simulated high-voltage electron
      micrographs. We perform arithmetic minimum filtering on stacks of aligned serial
      transmission electron microscopic images. In this way, the structural information
      of the separate images is fused into one compound image that highlights
      organization patterns otherwise easily overlooked or impossible to comprehend.
      Our method, like high-voltage electron microscopy, offers the possibility to
      build stereo-pairs for high-resolution three-dimensional analysis of tissue
      layers 1-2 microm thick. The use of background elimination and the development of
      a depth enhancement routine improved the three-dimensional effect and facilitated
      the analysis of the interior of objects. As an example, we use the method to
      display the distribution of axonal organelles at nodes of Ranvier and the shape
      and contents of a highly branched hippocampal dendritic spine.

PMID- 12005165
TI  - Role of matrix metalloproteinase-7 in angiogenesis associated with age-related
      macular degeneration.
AB  - To investigate the possible role of matrix metalloproteinase-7 in choroidal
      neovascularization associated with age-related macular degeneration,
      immunoelectron microscopy using ultrathin frozen sections and conventional
      transmission electron microscopy were performed in subfoveal fibrovascular
      membranes from patients with age-related macular degeneration. immunoelectron
      microscopy revealed that matrix metalloproteinase-7 was expressed within basal
      laminar deposits and amorphous materials around the retinal pigment epithelial
      cells. The results support a role for matrix metalloproteinase-7 in the
      development of choroidal neovascularization in age-related macular degeneration.

PMID- 12005166
TI  - Scanning electron microscopic observation of immunohistochemically specified
      stromal cells following the NaOH maceration method.
AB  - The present study introduces a method combining immunohistochemistry and a
      chemical digestion technique applied to scanning electron microscopy (SEM)
      observation of chemically characterized stromal cells in the myenteric layer of
      the monkey small intestine. The whole-mount preparation containing the myenteric
      layer was treated immunohistochemically using small colloidal gold and silver
      enhancements for detecting a certain type of stromal cell, followed by an alkali
      maceration method to remove extracellular matrices covering the
      immunohistochemically stained cells. This method permitted direct SEM observation
      of the stained stromal cells. Secondary and backscatter electron images clearly
      visualized the ultrastructure of the immunohistochemically-stained cells and the
      spatial distribution of the reaction products, respectively. It is suggested that
      the present method is useful for demonstrating the three-dimensional organization
      of the chemically specified stromal cells.

PMID- 12005167
TI  - Study of NADPH oxidase-activated sites in human neutrophils.
AB  - Neutrophils represent the first line of defence against invading microorganisms.
      An important part of this defence mechanism is the generation of superoxide (O2*
      ) and its reactive derivatives after stimulation by a variety of agents. This
      oxidant production is linked to the activation of NADPH oxidase, which is
      composed of cytosolic components (p47-phox and p67-phox) and membrane components
      (p22-phox and gp91-phox). Previous studies have shown that NADPH oxidase resides
      in the plasma membrane and the traditional view holds that cytoplasmic components
      of NADPH oxidase are brought into the neighbourhood of the plasma membrane and
      then conjugated with its membrane components upon stimulation. This review
      focuses on the evaluation of NADPH oxidase-activated sites in human neutrophils.
      Based on electron microscopic analysis, O2*- is first generated upon stimulation
      with certain stimulants, such as phorbol myristate acetate, within a specialized
      intracellular compartment containing alkaline phosphatase, and not on the plasma
      membrane, as previously thought. In addition, the cytosolic component of NADPH
      oxidase, p47-phox, accumulates at the juxtaposition of intracellular compartments
      but not of the plasma membrane. These results demonstrate that initial O2*-
      production occurs in an intracellular pool in human neutrophils. The oxidant
      producing granules then bind directly to the plasma membrane or fuse to form
      larger structures that eventually become to be associated with the plasma
      membrane, and O2*- is released extracellularly from the neutrophils.

PMID- 12005168
TI  - Recrystallization by annealing in SiC amorphized with Ne irradiation.
AB  - Alpha-silicon carbide was irradiated with Ne+ ions at room temperature to various
      fluences up to 7.5 x 10(20) Ne+ m(-2) and then isochronally annealed under
      observation with a transmission electron microscope. In all cases, thin regions
      were completely amorphized by irradiation and epitaxial growth occurred from the
      residual crystalline region by subsequent annealing. Crystal nucleation occurred
      with annealing at 1000 degrees C in the cases of 3.8 x 10(20) and 7.5 x 10(20)
      Ne+ m(-2) irradiation, and at 1100 degrees C in the cases of 1.3 x 10(20) and 2.3
      x 10(20) Ne+ m(-2) irradiation. Growth or formation of bubbles was observed with
      annealing at 1000 degrees C after 1.3 x 10(20), 2.3 x 10(20), and 3.8 x 10(20)
      Ne+ m(-2) irradiation.

PMID- 12005169
TI  - Resonance effect in ELNES from perovskite-type manganites BiMnO3 and LaMnO3.
AB  - Fine structures in electron energy-loss spectra, observed 30-40 eV beyond the
      threshold of oxygen K-edges in perovskite-type manganites BiMnO3 and LaMnO3, are
      discussed. LaMnO3 with orthorhombic symmetry (space group Pbnm) shows a clear
      peak in this region. However, BiMnO3 with a heavily distorted perovskite-type
      structure (monoclinic, space group C2) does not show an appreciable peak. It is
      demonstrated that peaks in this energy region arise from the resonance effect of
      ejected core electrons and that the shape is sensitive to the environment of
      neighbouring oxygen atoms in the perovskite-type structures.

PMID- 12005170
TI  - Repair of wounded monolayers of cultured bovine aortic endothelial cells is
      inhibited by calcium spirulan, a novel sulfated polysaccharide isolated from
      Spirulina platensis.
AB  - Calcium spirulan (Ca-SP) is a novel sulfated polysaccharide isolated from a blue
      green alga Spirulina platensis. Ca-SP inhibits thrombin by activation of heparin
      cofactor II. Therefore, it could serve as an origin of anti-atherogenic
      medicines. Since maintenance of vascular endothelial cell monolayers is important
      for prevention of vascular lesions such as atherosclerosis, the effect of Ca-SP
      at 20 microg/ml or less on the repair of wounded bovine aortic endothelial cell
      monolayers in culture was investigated in the present study. When the monolayers
      were wounded and cultured in the presence of Ca-SP, the polysaccharide inhibited
      the appearance of the cells in the wounded area. The inhibition was also observed
      even when the repair was promoted by excess basic fibroblast growth factor, which
      is one of the autocrine growth factors that are involved in the endothelial cell
      monolayer maintenance. On the other hand, Ca-SP inhibited the cell growth and the
      incorporation of [3H]thymidine into the acid-insoluble fraction of proliferating
      endothelial cells, suggesting that Ca-SP inhibits endothelial cell proliferation.
      From these results, it is concluded that Ca-SP may retard the repair process of
      damaged vascular endothelium through inhibition of vascular endothelial cell
      proliferation by induction of a lower ability to respond to stimulation by
      endogenous basic fibroblast growth factor.

PMID- 12005171
TI  - Absorption of intestinal free cholesterol is lowered by supplementation of Areca
      catechu L. extract in rats.
AB  - Areca extracts exhibiting a strong inhibitory activity against pancreatic
      cholesterol esterase (pCEase) in vitro were previously found to lower the
      absorption of dietary cholesteryl ester. Therefore, to determine whether a
      combined Areca extract also affects the absorption of intestinal free
      cholesterol, male rats were fed a diet containing free cholesterol (1%, w/w)
      either with or without an Areca nut extract supplement (0.5%, w/w). The Areca
      extract supplement significantly lowered the plasma cholesterol concentration by
      25% without any change in the plasma triglyceride concentration, when compared to
      the control group. The supplement also significantly lowered the small intestinal
      pCEase activity by 39.1% compared to that of the control group. As regards the
      hepatic and intestinal ACAT activities, only the intestinal enzyme activity was
      significantly lowered by the supplement, when compared to the control group. The
      absorbed cholesterol that appeared in the blood after an oral dose of [1,2(n)-3H]
      free cholesterol was significantly lower in the rats supplemented with the Areca
      nut extract, compared with the control group. These results suggest that the
      inhibition of intestinal ACAT and possibly pCEase may facilitate the metabolic
      efficiency of the Areca nut extract as regards the absorption of intestinal free
      cholesterol. The structure and chemical properties of the active compound in the
      water-soluble Areca extract remain to be elucidated.

PMID- 12005172
TI  - Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced
      nephrotoxicity: in comparison with rOAT1.
AB  - This study was performed to elucidate the possible involvement of organic anion
      transporter 3 (OAT3) in cephaloridine (CER)-induced nephrotoxicity and compare
      the substrate specificity between rOAT3 and rat OAT1 (rOAT1) for various
      cephalosporin antibiotics, using proximal tubule cells stably expressing rOAT3
      (S2 rOAT3) and rOAT1 (S2 rOAT1). S2 rOAT3 exhibited a CER uptake and a higher
      susceptibility to CER cytotoxicity than did mock, which was recovered by
      probenecid. Various cephalosporin antibiotics significantly inhibited both
      estrone sulfate uptake in S2 rOAT3 and para-aminohippuric acid uptake in S2
      rOAT1. The Ki values of CER, cefoperazone, cephalothin and cefazolin for rOAT3-
      and rOAT1-mediated organic anion transport ranged from 0.048 to 1.14 mM and from
      0.48 to 1.32 mM, respectively. These results suggest that rOAT3, at least in
      part, mediates CER uptake and CER-induced nephrotoxicity as rOAT1. There was some
      difference of affinity between rOAT3 and rOAT1 for cephalosporin antibiotics.

PMID- 12005173
TI  - Role of skeletal muscle Na+-K+ ATPase activity in increased lactate production in
      sub-acute sepsis.
AB  - Bacterial sepsis is frequently accompanied by increased blood concentration of
      lactic acid, which traditionally is attributed to poor tissue perfusion, hypoxia
      and anaerobic glycolysis. Therapy aimed at improving oxygen delivery to tissues
      often does not correct the hyperlactatemia, suggesting that high blood lactate in
      sepsis is not due to hypoxia. Various tissues, including skeletal muscle,
      demonstrate increased lactate production under well-oxygenated conditions when
      the activity of the Na+-K+ ATPase is stimulated. Although both muscle Na+-K+
      ATPase activity and muscle plasma membrane content of Na+, K+-ATPase subunits are
      increased in sepsis, no studies in vivo have demonstrated correlation between
      lactate production and changes in intracellular Na+ and K+ resulting from
      increased Na+-K+ pump activity in sepsis. Plasma concentrations of lactate and
      epinephrine, a known stimulator of the Na+-K+ pump, were increased in rats made
      septic by E. coli injection. Muscle lactate content was significantly increased
      in septic rats, although muscle ATP and phosphocreatine remained normal,
      suggesting oxygen delivery remained adequate for mitochondrial energy metabolism.
      In septic rats, muscle intracellular ratio of Na+:K+ was significantly reduced,
      indicating increased Na+-K+ pump activity. These data thus demonstrate that
      increased muscle lactate during sepsis correlates with evidence of elevated
      muscle Na+-K+ ATPase activity, but not with evidence of impaired oxidative
      metabolism. This study also further supports a role for epinephrine in this
      process.

PMID- 12005174
TI  - Scavenging of reactive oxygen species and prevention of oxidative neuronal cell
      damage by a novel gallotannin, pistafolia A.
AB  - Pistafolia A is a novel gallotannin isolated from the leaf extract of Pistacia
      weinmannifolia. In the present investigation, the ability of Pistafolia A to
      scavenge reactive oxygen species including hydroxyl radicals and superoxide anion
      was measured by ESR spin trapping technique. The inhibition effect on iron
      induced lipid peroxidaiton in liposomes was studied. The protective effects of
      Pistafolia A against oxidative neuronal cell damage and apoptosis induced by
      peroxynitrite were also assessed. The results showed that Pistafolia A could
      scavenge both hydroxyl radicals and superoxide anion dose-dependently and inhibit
      lipid peroxidation effectively. In cerebellar granule cells pretreated with
      Pistafolia A, peroxynitrite-induced oxidative neuronal damage and apoptosis were
      prevented markedly. The antioxidant capacity of Pistafolia A was much more potent
      then that of the water-soluble analog of vitamin E, Trolox. The results suggested
      that Pistafolia A might be used as an effective natural antioxidant for the
      prevention and cure of neuronal diseases associated with the production of
      peroxynitrite and related reactive oxygen species.

PMID- 12005175
TI  - Role of MAPK in chronic cerebral vasospasm.
AB  - This study was undertaken to investigate the role of p44/42 MAPK in a dog double
      hemorrhage model of subarachnoid hemorrhage (SAH), and whether MEK inhibitors can
      alter the degree of SAH-induced vasoconstriction. The diameter of the basilar
      artery, which was compared with day 0 angiogram, decreased gradually in a time
      dependent manner from day 3 (80%), day 5 (68%) through day 7 (53.5%). The level
      of MAPK (p44/42) immunoprecipitation peaked on day 3 and remained enhanced
      through day 7 (P < 0.05). MEK inhibitor PD98059 significantly reduced p44/42 MAPK
      immunoprecipitation and significantly reversed vasospasm and increased residual
      diameter to 79.0% on day 7. These results demonstrated that p44/42 MAPK kinase is
      involved in the pathogenesis of cerebral vasospasm. The MEK inhibitor PD98059
      might be useful in the treatment of vasospasm.

PMID- 12005176
TI  - Development of the corpus callosum in childhood, adolescence and early adulthood.
AB  - The corpus callosum (CC) is the major commissure connecting the cerebral
      hemispheres and there is evidence of its continuing development into young
      adulthood [Ann. Neurol. 34 (1993) 71]. Yet, little is known about changes in the
      size and tissue characteristics of its sub-regions. The sub-regions of the CC
      (genu, body, isthmus and splenium) are topographically organized to carry
      interhemispheric fibres representing heteromodal and unimodal cortical brain
      regions. Studies of the development of each of these sub-regions can therefore
      provide insights into the time course of brain development. We assessed age
      related changes in the size and the signal intensities (SI) of the subregions of
      the corpus callosum in the Magnetic Resonance Imaging (MRI) scans of a cross
      sectional sample of 109 healthy young individuals aged 7-32 years. Age was
      significantly positively correlated with the size of the callosal sub-regions
      (with the exception of the isthmus). On the other hand, there was an age-related
      decrease in SI across all the CC sub-regions. The rates of CC regional size
      increases appeared to be most pronounced in childhood. By contrast, SI decreases
      occurred during childhood and adolescence but reached an asymptote during young
      adulthood. Finally, the observed size and SI changes were similar across CC sub
      regions. The observed increases in CC size in conjunction with the decreases in
      signal intensity reflect continued maturation of the structure from childhood
      through young adulthood. An increase in axonal size may underlie growth in the
      size of the CC during childhood. The continued decrease in the CC signal
      intensity during adolescence may in addition be related to ongoing maturation of
      the axonal cytoskeleton. CC maturational changes appeared synchronous across sub
      regions suggesting parallel maturation of diverse brain regions during childhood
      and adolescence.

PMID- 12005177
TI  - Cytotoxic mechanism of Vibrio vulnificus cytolysin in CPAE cells.
AB  - Vibrio vulnificus is an estuarian bacterium that causes septicemia and serious
      wound infection. The cytolysin, one of the important virulence determinants in V.
      vulnificus infection, has been reported to have lethal activity primarily by
      increasing pulmonary vascular permeability. In the present study, we investigated
      the cytotoxic mechanism of V. vulnificus cytolysin in cultured pulmonary artery
      endothelial (CPAE) cells, which are possible target cells of cytolysin in vivo.
      V. vulnificus cytolysin caused the CPAE cell damages with elevation of the
      cytosolic free Ca2+, DNA fragmentation, and decrease of the cellular NAD+ and ATP
      level. These cytotoxic effects of V. vulnificus cytolysin were prevented by EGTA
      and aminobenzamide, but were not affected by verapamil or catalase. These results
      indicate that the elevation of cytosolic free Ca2+ induced by V. vulnificus
      cytolysin causes the increase of DNA fragmentation and the damaged DNA activates
      nuclear poly(ADP-ribose) synthetase, which depletes the cellular NAD+ and ATP,
      resulting in cell death.

PMID- 12005178
TI  - Trachea enhances neurite regeneration from adult rat nodose ganglia in vitro.
AB  - Trachea is intensely innervated with vagal afferent nerve fibers, and may play an
      important role in vagus nerve regeneration after axonal injury caused by trauma
      and surgical operation. We investigated the effects of tracheal tissue on
      neuronal cell survival and neurite regeneration in adult rat nodose ganglia (NG)
      in vitro. Co-culture with trachea significantly increased the average number of
      neurites regenerated from transected nerve terminals of NG explants, from 73.7 to
      154.2 after 3 days, from 68 to 186.7 after 5 days, and from 31 to 101.5 after 7
      days in culture. Dissociated NG neurons could continue to survive and extend
      neurites only in the co-existence with satellite cells in collagen gel. Co
      cultured trachea improved the ratios of survival and neurite-bearing cells of NG
      neurons, from 56.7% and 11.1% to 72.3% and 37.6% after 4 days, and from 41.1% and
      20.3% to 56.4% and 47.2% after 7 days in culture, respectively. These results
      imply that tracheal tissue secretes a factor, which could enhance neuronal cell
      survival and neurite regeneration in NG in the presence of satellite cells in
      vitro.

PMID- 12005179
TI  - Effect of intravenous bisphosphonates on release of basic fibroblast growth
      factor in serum of patients with cancer-associated hypercalcemia.
AB  - Basic fibroblast growth factor (bFGF) is a potent tumor angiogenesis factor and
      normal constituent of bone extracellular matrix which does not normally circulate
      in serum of nonpregnant adult humans. We examined the effects of acute
      administration of intravenous bisphosphonates on release of bFGF in human serum.
      Twenty seven men and women (mean age, 64 yr) with cancer-associated
      hypercalcemia, the majority of whom had osseous metastases, were treated once
      with an intravenous bisphosphonate. Nearly all twelve patients with elevated
      baseline serum bFGF ranging from 5-27 pg/mL showed significant decreases in serum
      bFGF (2-7 days) after iv bisphosphonate treatment. The mathematical product of
      the patients' initial serum bFGF and intial serum calcium concentration, the 'Ca
      x bFGF product', was significantly negatively (r = -0.91, P < 0.001) correlated
      with the acute change in serum bFGF level. No consistent relationship was
      observed between serum bFGF and serum parathyroid hormone related peptide (PTHrP)
      levels in the hypercalcemic cancer patients. In a subset of patients with non
      hematological malignancies and low baseline serum bFGF, acute changes in serum
      bFGF were significantly negatively (r = -0.66, P < 0.01) correlated with acute
      change in serum calcium concentration. These results indicate that release of
      bFGF in serum of patients with cancer-associated hypercalcemia likely depends
      predominantly on increased bone resorption. Acute change in low serum levels of
      bFGF in patients with cancer-associated hypercalcemia treated with intravenous
      bisphosphonates may be physiologically inversely regulated by acute change in the
      serum calcium concentration.

PMID- 12005180
TI  - The endocrine disruptor nonylphenol preferentially blocks cyclooxygenase-1.
AB  - The anthropogenic chemicals nonylphenol, bisphenol A, phthalic acid benzyl n
      butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl)
      ester have been shown to possess sex hormone-like activity. To explore the
      possible actions of these chemicals on the autacoid synthesis in the body, we
      investigated the effects of nonylphenol, bisphenol A, phthalic acid benzyl n
      butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl)
      ester on the activities of cyclooxygenase-1 and -2. Bisphenol A and all three
      phthalic acid derivatives had no significant effect on the cyclooxygenase-1 and 
      2 activities up to 100 microM. On the other hand, nonylphenol exhibited a marked
      inhibition on the cyclooxygenase-1 activity (10-100 microM nonylphenol, 7-95%
      inhibition), with no detectable change in the activity of cyclooxygenase-2. The
      inhibition patterns for the substrate, arachidonic acid, and a cofactor, phenol,
      were competitive and uncompetitive, respectively. These results suggest that
      nonylphenol can be a selective inhibitor of cyclooxygenase-1 activity.

PMID- 12005181
TI  - Effects of long-chain fatty alcohol on peripheral nerve conduction and bladder
      function in diabetic rats.
AB  - Diabetic cystopathy as manifested by an enlarged bladder is mainly caused by
      peripheral neuropathy. Long-chain fatty alcohol, which has been isolated from the
      Far-Eastern traditional medicinal plant, Hygrophilia erecta, Hochr., has been
      found to possess some neurotrophic activities on the central neuron.
      Cyclohexenonic long-chain fatty alcohol (FA) used in this study were synthesized
      in order to improve the efficiency of the molecules. The effects of this compound
      on peripheral nerves, however, have not yet been studied. To get more
      information, we evaluated the effects of this compound on peripheral nerves in
      streptozotocin-induced diabetic rats in terms of nerve conduction velocity and
      bladder function. Three experiments were performed 8 weeks after the
      administration of streptozotocin to 8-week-old rats: (i) motor sciatic nerve
      conduction (MNCV), (ii) monitoring micturition behavior in the metabolic cage,
      and (iii) cystometrogram under urethane anesthesia (CMG). Half of the diabetic
      rats were treated with FA (8 mg/kg/day, i.p.). The difference in MNCV between
      control rats (49.0 +/- 2.2 m/s) and untreated diabetic rats (42.4 +/- 0.5 m/s)
      after 8 weeks reached significance (p = 0.0183). FA-administrated diabetic rats
      showed an improved MNCV (45.8 +/- 1.2 m/s). We also identified a significant
      improvement of bladder function in these animals. The diabetic rats had a much
      higher maximal micturition volume per 24 hours (4.9 +/- 0.4 ml) than control
      animals (1.5 +/- 0.1 ml). However, the diabetic rats treated with FA had a
      maximal micturition volume of only 3.7 +/- 0.3 ml. Likewise, the diabetic rats
      had a CMG bladder capacity of 0.90 +/- 0.14 ml while the diabetic rats treated
      with FA had a capacity of 0.54 +/- 0.07 ml. These results indicate that
      cyclohexenonic long-chain fatty alcohol has a beneficial effect on peripheral
      neuropathy and cystopathy in streptozotocin-induced diabetic rats.

PMID- 12005182
TI  - Sulfite induces adherence of polymorphonuclear neutrophils to immobilized
      fibrinogen through activation of Mac-1 beta2-integrin (CD11b/CD18).
AB  - Sulfite is a major air pollutant which can cause respiratory tract inflammation
      characterized by an influx of polymorphonuclear neutrophils (PMN). We have
      previously shown that human PMN can produce sulfite either spontaneously or in
      response to stimulation with lipopolysaccharide. We now demonstrate that sulfite
      activates PMN to adhere to immobilized fibrinogen via the beta2-integrin Mac-1
      (CD11b/CD18). Mac-1 expression is not altered by treatment with this agent.
      Although unaffected by pertussis toxin, sulfite-triggered PMN adhesion was
      abrogated by pretreating cells with the membrane-impermeant sulfhydryl reagent
      5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), a modifier of thiol groups on the
      cell surface. These results suggest that sulfite-induced PMN adhesion is
      dependent on a modification of thiols at the cell surface. Given its potent
      antioxidant and antimicrobial activities, sulfite may act as an endogenous
      mediator in host defense and/or inflammation.

PMID- 12005183
TI  - Effects of Cl- channel blockers on endothelin-1-induced proliferation of rat
      vascular smooth muscle cells.
AB  - The effects of Cl- channel blockers on endothelin-1 (ET-1)-induced proliferation
      of rat aortic vascular smooth muscle cells (VSMC) were examined. We found ET-1
      concentration-dependently increased cell count and [3H]-thymidine incorporation
      into VSMC, with EC50 values of 24.8 and 11.4 nM, respectively. Both nifedipine
      and SK&F96365 inhibited 10 nM ET-1-induced [3H]-thymidine incorporation into VSMC
      with the maximal inhibitory concentrations of 1 and 10 microM, respectively. DIDS
      inhibited 10 nM ET-1-induced increase in cell count and [3H]-thymidine
      incorporation into VSMC in a concentration-dependent manner, whereas other Cl-
      channel blockers including IAA-94, NPPB, DPC, SITS and furosemide did not produce
      these effects. 3 microM DIDS reduced 10 nM ET-1-induced sustained increase in
      cytoplasmic Ca2+ concentration ([Ca2+]) by 52%. Pretreatment of VSMC with 1
      microM nifedipine completely inhibited the DIDS effect on 10 nM ET-1-induced [3H]
      thymidine incorporation into VSMC and sustained increase in [Ca2+]i, whereas
      pretreatment with 10 microM SK&F96365 did not completely block these effects of
      DIDS. DIDS did not affect ET-1-induced Ca2+ release and 30 mM KCl-induced
      increase in [Ca2+]i. Our data suggest that DIDS-sensitive Cl- channels mediate
      VSMC proliferation induced by ET-1 by mechanisms related to membrane
      depolarization and Ca2+ influx through voltage-dependent Ca2+ channels.

PMID- 12005184
TI  - Different diets and amino acid supplementation do not affect the voluntary
      consumption of ethanol by rats.
AB  - The effects of four different diets (control diet: 19.5% protein, 60.5%
      carbohydrate, 10% fat; diet I: 65% protein, 10% carbohydrate, 10% fat; diet II:
      5% protein, 76% carbohydrate, 10% fat; diet III: 20% protein, 69% carbohydrate,
      1% fat; diet IV: 69% protein, 15% carbohydrate, 1% fat) and supplementation with
      3 amino acids (tryptophan: 150 mg/kg/d; arginine: 400 mg/kg/d; taurine: 380
      mg/kg/d) on the voluntary consumption of ethanol were investigated in rats using
      the 2 bottle method. First, rats received the control diet and diets I, II, III
      and IV for 20 days with a choice of ethanol for the last 6 days only. Ethanol
      consumption was similar in all dietary groups. Second, rats received the control
      diet for 8 days followed by diets I, II and IV for another 8 days. Ethanol was
      offered throughout both periods. The switch to the special diets did not affect
      ethanol consumption. Third, rats received a control diet with arginine,
      tryptophan or taurine added to the drinking fluids for 16 days with a choice of
      ethanol for the last 5 days; thereafter supplementation stopped but the ethanol
      choice remained. No difference in the voluntary intake of ethanol was noted but
      ethanol consumption fell after cessation of arginine supplementation. In
      conclusion, diets differing greatly in their composition or supplementation with
      these 3 amino acids did not affect the voluntary choice of ethanol by rats in a
      significant manner.

PMID- 12005185
TI  - Arsenic trioxide-induced apoptosis through oxidative stress in cells of colon
      cancer cell lines.
AB  - Exposure of three colon cancer cell lines, SW480, DLD-1, and COLO201, to arsenic
      trioxide in the medium induced a marked concentration-dependent suppression of
      cell growth. The intracellular contents of reduced glutathione (GSH) in these
      cell lines tended to be inversely correlated with the sensitivity of the cells to
      arsenic trioxide. Among the cell lines, SW480 cells underwent apoptosis at the
      low arsenic trioxide concentration of 2 microM, which was prevented by
      pretreatment of the cells with N-acetylcysteine and was enhanced by buthionine
      sulfoximine. The production of reactive oxygen intermediates which were examined
      by 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time
      after treatment with arsenic trioxide. The apoptosis was executed by the
      activation of caspase 3, which was shown by Western blot, enzymatic activity, and
      apoptosis inhibition assay. The mitochondrial membrane potential of adherent
      apoptotic SW480 cells and the cells from intermediate layer separated by density
      gradient centrifugation, both of which showed the active form of caspase 3 by
      Western blot analysis, was not lost. The overexpression of Bcl-2 protein in SW480
      cells could not prevent the apoptosis induced by the treatment with arsenic
      trioxide. All these findings indicate that arsenic trioxide-induced apoptosis in
      SW480 cells is executed by the activation of caspase 3 without mediating by
      mitochondria under the overproduction of reactive oxygen species.

PMID- 12005186
TI  - Disruption of sensitization to methylphenidate by a single administration of MK
      801.
AB  - Blockade of sensitization to methylphenidate by a single injection of MK-801 was
      investigated using a computerized activity monitoring system. Male Sprague-Dawley
      rats were housed in test cages and motor activity was recorded continuously for
      16 days. After 2 days of baseline recording and a saline injection on day 3, the
      rats were randomly divided into four experimental groups. All received 2.5 mg/kg
      of methylphenidate (s.c.) once a day from days 4 to 9, then after five days of no
      treatment, they were re-challenged with 2.5 mg/kg of methylphenidate on day 15.
      One group received only methylphenidate, while the other three groups also
      received a single i.p. injection of MK-801 (0.30 mg/kg) either 24 h (day 3) or 1
      h prior to the first of the six methylphenidate injections (day 4), or 1 h prior
      to the second methylphenidate injection (day 5). A single injection of MK-801 on
      day 4 (1 h prior to methylphenidate) blocked the development of sensitization to
      methylphenidate, since a sensitized response could not be elicited six days after
      cessation of repeated methylphenidate administration (day 15). However,
      sensitization to methylphenidate still occurred in the groups receiving MK-801
      (0.30 mg/kg) on day 5, indicating that the mechanism by which a single injection
      of MK-801 disrupts sensitization to methylphenidate is sensitive to timing and is
      not a direct long-term effect. In conclusion, a single injection of MK-801
      persistently blocks the development of sensitization to methylphenidate only if
      it is given with methylphenidate on the first day of the repetitive treatment
      phase.

PMID- 12005187
TI  - Antioxidant effects of phyto-and synthetic-estrogens on cupric ion-induced
      oxidation of human low-density lipoproteins in vitro.
AB  - Oxidation of low-density lipoproteins (LDL) promotes the formation of
      atherosclerotic plaques. Estrogenic compounds (EC) from foods and other natural
      products, and synthetic estrogenic compounds (SECs) may prevent heart disease by
      inhibiting LDL oxidation. In the present study, we tested the antioxidant
      capacities of two phytoestrogens, daidzein (DAI) and genistein (GEN), and four
      SECs, (+)- and (-)-Z-bisdehydrodoisynolic acid (ZBDDA), and (+)- and (-)-hydroxy
      allenoic acid (HAA), on isolated human LDL subjected to oxidation by cupric
      sulfate. The effects of these estrogenic compounds on the kinetics of conjugated
      diene formation in LDL undergoing oxidation were evaluated with a lag-time assay
      with continuous monitoring of absorbance at 234 nm. Lag-time data revealed that
      (+)-HAA, (-)-HAA, (+)-ZBDDA, and (-)-ZBDDA had similarly stronger antioxidant
      activities than either GEN or DAI. We also found that (+)-HAA, (-)-HAA, (+)
      ZBDDA, and (-)-ZBDDA strongly inhibited the formation of Cu+-induced
      thiobarbituric acid reactive substances (TBARS) in LDL, and that GEN and DAI were
      less effective for inhibiting LDL lipid peroxidation. Finally, electrophoretic
      evaluation suggested that (+)-HAA, (-)-HAA, (+)-ZBDDA, and (-)-ZBDDA protected
      the apolipoprotein B-100 of LDL against oxidation better than did GEN or DAI. In
      summary, the four SECs, (+)-HAA, (-)-HAA, (+)-ZBDDA, and (-)-ZBDDA, were more
      potent antioxidants than the phytoestrogens, DAI and GEN.

PMID- 12005188
TI  - Influence of 4-week and 8-week exercise training on the pharmacokinetics and
      pharmacodynamics of intravenous and oral azosemide in rats.
AB  - Cytochrome P450 expression was determined in the livers of control, 4-week
      exercised (4WE) and 8-week exercised (8WE) rats. Even though the 4-week and 8
      week exercise training caused 53 and 25% increases, respectively, in total
      cytochrome P450 contents in the liver, exercise training did not cause any
      changes in the levels of P450 1A2 (which primarily metabolizes azosemide), 2E1
      and 3A23 in the liver, as assessed by both Western and Northern blot analyses.
      Also, exercise training failed to alter the activity of NADPH-dependent
      cytochrome P450 reductase. The plasma concentrations of norepinephrine and
      epinephrine were significantly (2 to 3 folds) higher in 4WE rats than in
      controls, presumably due to physical stress, but the catecholamine levels in 8 WE
      rats returned to control levels. After intravenous administration (10 mg/kg of
      azosemide), the amount of unchanged azosemide excreted in 8-h urine (Ae(Azo, 0-8
      h)) was significantly greater (46% increase) in 4WE rats than that in control
      rats. This resulted in a significantly faster (82% increase) renal clearance of
      azosemide. However, the nonrenal clearances were not significantly different
      between control and 4WE rats. The significantly greater Ae(Azo, 0-8 h) in 4WE
      rats was mainly due to a significant increase in intrinsic active secretion of
      azosemide in renal tubules and not due to a decrease in the metabolism of
      azosemide. After oral administration (20 mg/kg), Ae(Azo, 0-8 h) was also
      significantly greater (264%) in 4WE rats and this again was due to a significant
      increase in intrinsic active renal secretion of azosemide and not due to an
      increase in gastrointestinal absorption. After both intravenous and oral
      administration, the 8-h urine output was not significantly different between
      control and 4WE rats although Ae(Azo, 0-8 h) increased significantly in 4WE rats.
      This could be due to the fact that the urine output reached a plateau at 10 mg/kg
      after intravenous administration and 20 mg/kg after oral administration of
      azosemide to rats and possibly due to increase in plasma antidiuretic hormone
      levels and aldosterone production in 4WE rats.

PMID- 12005189
TI  - Characterization of hypoxia-induced [Ca2+]i rise in rabbit pulmonary arterial
      smooth muscle cells.
AB  - We have investigated the effects of hypoxia on the intracellular Ca2+
      concentration ([Ca2+]i) in rabbit pulmonary (PASMCs) and coronary arterial smooth
      muscle cells with fura-2. Perfusion of a glucose-free and hypoxic (PO2<50 mmHg)
      external solution increased [Ca2+]i in cultured as well as freshly isolated
      PASMCs. However it had no effect on [Ca2+]i in freshly isolated coronary arterial
      myocytes. In the absence of extracellular Ca2+, hypoxic stimulation elicited a
      transient [Ca2+]i increase in cultured PASMCs which was abolished by the
      simultaneous application of cyclopiazonic acid and ryanodine, suggesting the
      involvement of sarcoplasmic reticulum (SR) Ca2+ store. Pretreatment with the
      mitochondrial protonophore, carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)
      enhanced the [Ca2+]i rise in response to hypoxia. A short application of caffeine
      gave a transient [Ca2+]i rise which was prolonged by CCCP. Decay of the caffeine
      induced [Ca2+]i transients was significantly slowed by treatment of CCCP or
      rotenone. After full development of the hypoxia-induced [Ca2+]i rise, nifedipine
      did not decrease [Ca2+]i. These data suggest that the [Ca2+]i increase in
      response to hypoxia may be ascribed to both Ca2+ release from the SR and the
      subsequent activation of nifedipine-insensitive capacitative Ca2+ entry.
      Mitochondria appear to modulate hypoxia induced Ca2+ release from the SR.

PMID- 12005190
TI  - Zero loss peak deconvolution for bandgap EEL spectra.
AB  - This paper shows how bandgap EEL spectra are commonly processed either by
      deconvolution or subtraction methods in an attempt to remove effects arising from
      the finite width and long tail of the zero loss peak. This paper will compare the
      two main methods, and show that the deconvolution method is significantly more
      reliable and free of user-interpretation or artefacts. We first consider how the
      zero loss peak is produced and what effects experimental conditions have upon it,
      and then show that only by the deconvolution method can accurate bandgap energies
      and bandgap densities of states be determined.

PMID- 12005191
TI  - Application of spline wavelet transformation to the analysis of extended energy
      loss fine structure.
AB  - We propose a new analysis method of the extended energy-loss fine structure
      (EXELFS), applying the multi-resolution analysis (MRA) in the wavelet
      transformation. We select the cardinal spline wavelet where the rank-4 cardinal
      spline function is used as a scaling function to construct the mother wavelet. In
      contrast with the conventional analysis method, the present method is efficient
      in filtering out the high-frequency noise and low-frequency components introduced
      by the numerical analysis process without distorting the original signal
      components, which promises quantitative analyses with less uncertainties.

PMID- 12005192
TI  - Morphological effects of an anabolic steroid on muscle fibres of the diaphragm in
      mice.
AB  - Until recently, rats have been used for studies on the effects of anabolic
      steroids (AS) for improving physical performance. However, no consistent results
      on the changes in muscle fibre volume have ever been obtained. In this study we
      investigated the morphological effects of nandrolone phenylpropionate, an AS, on
      the muscle fibres of the diaphragm in adult male mice. AS (5 mg kg(-1) week(-1))
      was injected intramuscularly in the experimental group (AS-administration group),
      and peanut oil (0.08 ml week(-1)) was injected in the control group. The cross
      sectional areas of Type I (red) and Type II (white and intermediate) muscle
      fibres after 4 weeks of AS administration were 135% and 139% larger than those in
      the control group, respectively. The mean cross-sectional areas of mitochondria
      in the subsarcolemmal (SS) region and interfibrillar (IF) region in Type I fibres
      and the SS region of the Type II muscle fibres in the AS-administration group
      were 139%, 135% and 124% larger than those in the control group, respectively. No
      significant differences in the cross-sectional area of mitochondria were noted
      between the group of mice administered with AS for 8 weeks and the control group,
      showing that the effect of the AS administration attained a peak at 4 weeks, but
      that the effect of the 8 weeks of AS administration declined. We concluded from
      these results that the response of Type I muscle fibres to AS is stronger than
      that of Type II muscle fibres, as is the response of SS mitochondria compared to
      IF mitochondria. We also suggested that the two types of mitochondria may have
      different roles and that administration of AS may cause a different response in
      the two types of mitochondria.

PMID- 12005193
TI  - Improved ultrastructure of the desmosome-intermediate filament complex in MCF-7
      breast cancer cells.
AB  - We report on the application of variations to the traditional TEM processing
      methods, which provide improved clarity of the desmosome-cytoskeleton complex of
      MCF-7 human breast cancer cells. A more comprehensive understanding of the
      ultrastructure is presented, which in the past has been demonstrated in
      diagrammatic form based on numerous electron micrographs. Ultrastructural
      analysis shows that intermediate filament bundles do not terminate at the
      desmosome structure, but instead are continuous into the cytoplasm. Furthermore
      only a minor proportion of individual filaments are in actual contact with the
      desmosome plaque. Intermediate filaments were also observed throughout the
      cytoplasm and to the surface of the nuclear membrane. Extraction protocols
      allowed clear identification of other cellular features such as nuclear pores,
      which are approximately 80-85 nm in diameter, and were best viewed in sections
      cut tangentially to the nuclear surface.

PMID- 12005194
TI  - The use of nonparametric statistics in quantitative electron microscopy.
AB  - Parametric statistical methods assume samples that have a normal distribution and
      representative sample sizes (i.e. n >20). Quantitative electron microscopy is
      inherently restricted to small sample sizes and a priori there is no way to know
      if the expression of the ligand being studied has a normal distribution. Thus to
      make statistical inferences based on data generated by quantitative electron
      microscopy using parametric methods may not be justified. Nonparametric
      statistical methods offer a tool for the evaluation of data that do not meet the
      criteria for analysis by parametric methods. In this report I show the utility of
      using nonparametric statistical methods for the analysis of data generated by
      quantitative electron microscopy.

PMID- 12005195
TI  - A new method for detecting and localizing cell markers endocytosed by fibroblasts
      in epoxy resin semi-thin sections using scanning electron microscopy combined
      with energy dispersive X-ray microanalysis after ion-etching.
AB  - Cell marking is widely used to examine cell development and differentiation in
      developmental biology. We developed a new method for localizing cell markers in a
      semi-thin epoxy section with scanning electron microscopy. Cultured fibroblasts
      ingesting carbon particles were autologously transplanted into a rabbit
      transparent ear chamber, 6 mm in diameter and 100 microm in depth. Eight days
      after the transplantation, tissues in the chamber were fixed and embedded in
      epoxy resin. Semi-thin sections were cut and stained with toluidine blue.
      Fibroblasts in connective tissues which contained black spots were observed with
      a light microscope. These sections were subsequently ion-etched with an ion
      coater and coated with platinum. The same fibroblasts were then visualized by
      secondary electron imaging using a scanning electron microscope. A nucleus with
      nuclear envelope, nuclear pores, a nucleolus and heterochromatin, mitochondria
      with cristae and rough endoplasmic reticulum were observed in the fibroblasts.
      The black spots in the fibroblasts were identified as bright bodies with the
      scanning electron microscope. The bright bodies were found to be a lump of tiny
      particles less than 100 nm in diameter. In order to analyse such particles with
      energy dispersive X-ray microanalysis, ion-etched sections were coated with
      carbon. X-ray energy spectrometry clearly demonstrated that these were carbon
      particles, which had been endocytosed by the fibroblast. This suggests that
      scanning electron microscopy combined with energy dispersive X-ray microanalysis
      is useful for detecting carbon particles in the cytoplasm at an ultrastructural
      level in semi-thin epoxy sections subsequent to ion etching and that this method
      may be applicable to other cell markers, such as gold particles to track cells in
      the field of cell development and cell differentiation.

PMID- 12005196
TI  - The solar cell in hornet cuticle: nanometer to micrometer scale.
AB  - This paper focuses on structures observed by scanning and transmission electron
      microscopy and atomic force microscopy upon and within the abdominal cuticle of
      the Oriental hornet, Vespa orientalis. Taken together, these structures form an
      'organ' whose function is the absorption ef sunlight and storage of the resultant
      electrical energy. In principle, this organ resembles a solar cell. The gaster of
      the hornet is cone-shaped and comprised of the following components: (i)
      structures protruding from the epicuticular surface, which are arranged
      lengthwise and generally parallel to one another like furrows; (ii) these furrows
      overlie straight, terrace-like flat surfaces, which are shaped like imperfect
      polygons, each about 100 microm2 in area; (iii) each terrace abuts an area that
      is positioned lower than it, the juncture between the two is comprised of a
      stripe, which is vertical to the topmost polygonal flat and perpendicular to the
      furrows; (iv) between the juncture stripes, at distances of 10-100 microm apart,
      there are smooth flat surfaces reminiscent of a parabolic mirror of about 20
      microm2, each possessing a rounded, eccentric area recessed to a depth of about
      7.5 microm (i.e. a heat sinking housing), underneath which can be seen the upper
      part of the peripheral photoreceptor (PP); (v) cuticular lamellae, about 30 in
      number, create a pore between them in the PP region, fold in vertical fashion and
      enwrap the entire PP down to its broad base which is immersed in a yellow
      bacterial layer and where the cuticular layers are very thin. Presumably the
      light energy impinges vertically upon the individual terraced flat surfaces while
      the hornet is in flight, creating such situations for a fraction of a second at a
      time. The insolation is absorbed more intensively in the furrows, owing to their
      shape. The picked up solar energy is now transmitted as electric charges from the
      furrows to the conduction stripes between abutting terraces, and thence to: (a)
      the rhodopsin pigment in the PP (the smaller moiety), or (b) the numerous
      cuticular layers, depending on the energy level of the picked up photons (the
      larger moiety), and (c) finally to the bacterial layer for storage in its walls.
      The latter region will be a p-type as compared to the energy stored in the layers
      of brown cuticle. The cuticle thus was found to contain many PPs but within the
      cuticle they are dispersed in contrast to the situation in the compound eye,
      where the many photoreceptors are concentrated.

PMID- 12005197
TI  - Abnormal formation of the glucan network from regenerating protoplasts in
      Schizosaccharomyces pombe cps8 actin point mutant.
AB  - To study the close relationship between the actin cytoskeleton and cell wall
      formation, the process of cell wall formation in reverting protoplasts of the
      fission yeast, Schizosaccharomyces pombe, cps8 actin point mutant was
      investigated by ultra-high-resolution low-voltage scanning electron microscopy
      (UHR-LVSEM) and transmission electron microscopy (TEM). The protoplast of the
      cps8 mutant began to form a glucan network in a unipolar manner and to secrete
      alpha-galactomannan. The site of cell wall formation grew in a cylindrical shape
      in the wild-type protoplast. The alpha-galactomannan did not fill in the
      intrafibrillar spaces completely, however, and the fibrils were exposed on the
      cell surface. UHR-LVSEM images indicated that the glucan fibrils were thin and
      rope-shaped, forming a looser network than the wild-type. TEM images indicated
      the finest fibrils were approximately 1.5 nm in diameter, the same diameter as
      the wild-type. These results suggest that the cps8 mutant was insufficient in
      developing cross-linkage with the glucan fibrils up to the wide ribbon shape as
      found in the wild-type [Osumi M et al. (1989) J. Electron Microsc. 38: 457-468;
      Osumi M (1998) Micron 29: 207-233]. These findings appear to indicate that the
      actin cytoskeleton controls formation of the glucan network and secretion of beta
      1,6-glucan, and confirm the close relationship of the actin cytoskeleton and
      glucan formation.

PMID- 12005198
TI  - High-resolution ultrastructure of amyloid fibrils in familial amyloid
      polyneuropathy.
AB  - The ultrastructure of amyloid fibrils in familial amyloid polyneuropathy (FAP)
      was clearly demonstrated. Amyloid of three patients with FAP caused by the point
      mutation of the 30th amino acid of transthyretin (ATTR Val30Met) and one patient
      with FAP caused by two point mutations of the 30th and 104th amino acid of
      transthyretin (ATTR Val30Met/Arg104Cys) were partially isolated, stained
      negatively and examined with an electron microscope. Amyloid fibrils of both
      types were composed of two protofilaments and twisted at 180 degrees to the right
      and left alternately with a periodicity of 125-135 nm. This is the first report
      demonstrating such unique alternating twist structure of amyloid fibrils. There
      were no ultrastructural differences between the fibrils caused by the ATTR
      Val30Met and ATTR Val30Met/ Arg104His; therefore, it is suggested that the point
      mutation of the 30th amino acid of transthyretin might play an important role in
      the formation of amyloid fibrils. Further biochemical study on the mechanism of
      this alternating twist formation should be undertaken.

PMID- 12005199
TI  - The 11 A resolution projection map of Na+/K+-ATPase calculated by application of
      single particle analysis to two-dimensional crystal images.
AB  - Two-dimensional (2D) crystals of Na+/K+-ATPase were vitrified and observed with
      an electron cryo-microscope that allowed specimen observation at liquid helium
      temperature. Images showing 19 A spots on the optical diffraction patterns were
      digitized and processed by a crystallographic method. After optimization of
      parameters for the image processing, the locally averaged images revealed that
      each 2D crystal contained heterogeneous molecules. Single particle analysis was
      therefore applied to the 2D crystal images to select homogeneous molecule images,
      and averaging the selected images significantly improved map quality. Five major
      peak densities were clearly resolved in the new projection map, while two were
      found previously.

PMID- 12005200
TI  - Hyaluronan molecular weight and polydispersity in some commercial intra-articular
      injectable preparations and in synovial fluid.

PMID- 12005201
TI  - Acarbose related diarrhea: increased butyrate upregulates prostaglandin E.
AB  - The alpha-glucosidase inhibitor acarbose is a drug used to treat type II diabetes
      mellitus. It occasionally causes diarrhea. Acarbose related colitis has been
      reported. This note explains how such side effects may occur. Because of small
      intestine alpha-glucosidase inhibition, increased starch reaches the colon.
      Increased colonic starch allows the flora to generate increased butyrate.
      Absorbed butyrate causes up-regulation of prostaglandin E series production and
      the latter generates water and electrolyte loss. A colitis results when this
      acarbose driven process is extreme. Acarbose should be avoided in pregnancy until
      above can be disproved due to teratogenic and labor inducing potential of
      prostaglandin E. A theoretical reason for avoiding acarbose in Crohn's disease is
      presented. Despite these considerations, acarbose remains a safe medicine and may
      even have salutary intestinal consequences stemming from the same physiology as
      outlined here.

PMID- 12005202
TI  - Molecular aspects of anti-inflammatory action of G-CSF.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a cytokine which stimulates the
      production of neutrophils in the bone marrow and modulates cellular functions of
      mature neutrophils. Besides neutrophils and their precursors, monocytes are
      direct target cells of G-CSF action. G-CSF influences monocyte functions in an
      anti-inflammatory way: The stimulation of monocytes with G-CSF results in an
      attenuation of LPS-induced release of IL-1beta, TNF-alpha, IL-12 and IL-18. G-CSF
      exerts its biological functions on neutrophils and monocytes via membrane-bound
      receptors. Seven different human G-CSF receptor isoforms have been described
      which are generated by alternative splicing. The physiologic roles of these
      isoforms and the expression pattern on various cell types are still unknown. The
      signal transduction pathway of G-CSF receptors involves the activation of JAK
      tyrosine kinases and STAT transcription factors and the ras/mitogen-activated
      protein kinase pathway.

PMID- 12005203
TI  - Antithrombotic and platelet function inhibiting effects of ML3000, a new
      antiinflammatory drug with Cox/5-LOX inhibitory activity.
AB  - DESIGN: The studies reported were designed to evaluate the effects of ML3000 on
      platelet aggregation and platelet-induced thrombin generation in human platelet
      rich plasma and its antithrombotic effect in a rat thrombosis model. ML3000 is a
      potent inhibitor of both COX-1/2 and 5-LOX with demonstrated antiinflammatory
      activity and a low incidence of GI mucosal injury in animal and human studies.
      METHODS AND RESULTS: The antithrombotic activity of ML3000 (10, 30 and 100 mg/kg)
      and aspirin (30 and 100 mg/kg) was measured in the mesenteric venules of rats
      using the laser-induced thrombus model. Both ML3000 and aspirin, at all doses
      tested, showed significant antithrombotic activity. The mean number of laser
      injuries necessary to induce a thrombus that blocked the vessel was 1.93 +/- 0.28
      in the control group, 3.3 +/- 0.53, 3.6 +/- 0.14 or 4.07 +/- 0.37 in the groups
      treated with ML3000 at 10, 30 or 100 mg/kg p.o. and 3.4 +/- 0.55 or 3.9 +/- 0.3
      in the groups treated with Aspirin at 30 or 100 mg/kg p.o. The antithrombotic
      activity in this model was significant up to 12 h post-administration of 100
      mg/kg ML3000 or Aspirin. The aggregation inhibiting activity of ML3000 (1-100
      microg/ml) and indomethacin (1 microg/ml) was studied using the following
      inducing agents: ADP (1 and 2 microM), epinephrine (25 and 50 microM), collagen
      (0.5 and 1 microg/ml), and the thromboxane mimetic U46619 (0.8 and 1.6 microM).
      Aggregation inhibitory activity was observed with ML3000 in all assays except
      with the higher concentration of U46619 at 1.6 microM. Indomethacin (1 microg/ml)
      inhibited aggregation in all assays. CONCLUSIONS: ML3000 has significant
      antithrombotic activity and a marked platelet aggregation inhibiting effect.
      Given its demonstrated antiinflammatory activity, platelet function inhibition,
      and antithrombotic effects along with a lack of effect on the GI mucosa, ML3000
      may offer an alternative to the combination of a COX-2 inhibitor and aspirin in
      arthritis patients at risk for cardiovascular disease.

PMID- 12005204
TI  - The mechanism of action of the new antiinflammatory compound ML3000: inhibition
      of 5-LOX and COX-1/2.
AB  - OBJECTIVE: We examined the effects of ML3000 and several non-steroidal
      antiinflammatory drugs (NSAIDs) on the synthesis of products of 5-LOX (LTB4,
      LTC4) and COX-1/2 (TXB2, PGE2) in vitro and ex vivo in order to further elucidate
      the mechanism of action of ML3000. METHODS AND RESULTS: Using a human whole blood
      assay the effect of ML3000 on the shunt of arachidonic acid to the lipoxygenase
      pathway when COX is blocked was studied. ML3000 (0.3, 1, 3, 10, 30 microg/ml) and
      indomethacin (0.3, 1, 3, 10, 30 microg/ml) concentration-dependently inhibited
      the synthesis of PGE2 (IC50 = 3.9 and 4.5 microM). In contrast to ML3000,
      indomethacin produced an increase of LTC4 of up to 155.5% of control. 5
      lipoxygenase inhibition was further tested in a basophilic leukemia cell assay
      using RBL-1 cells. ML3000 (1-10 microM) inhibited the synthesis of LTB4 in a
      concentration related manner (IC50: 3.6 microM). In carrageenan induced rat paw
      edema, ML3000 and indomethacin completely blocked the formation of PGE2 in the
      inflamed tissue. The LTB4 production in the inflamed paw was reduced to basal
      levels by ML3000 (10 +/- 1.4 pg/paw saline control and 7.5 +/- 1.3-5.9 +/- 3.2
      pg/paw ML3000), whereas LTB4 levels remained markedly elevated as compared to
      saline control by indomethacin (30.7 pg/paw). 5-LOX inhibition in the inflamed
      rat colon was investigated by measuring LTB4 synthesis. MK-886 and ML3000 at 10
      mg/kg p.o. reduced LTB4 production to 29.8 +/- 4.9 and 30.1 +/- 2.8 pg/mg tissue
      as compared to control (54.2 +/- 7.4 mg/kg tissue). LTB4 levels in the rat
      stomach were comparable to control (2.5 +/- 0.4 pg/mg protein) after oral
      administration of ML3000 (10, 30, 100 mg/kg), whereas oral treatment with
      indomethacin (0.3, 1, 3 mg/kg) or diclofenac (1, 3 mg/kg) increased LTB4 up to
      9.2 +/- 2.3 or 8.9 +/- 1.6 pg/mg protein. This effect was significant at 1 mg/kg
      diclofenac and 0.3 mg/kg indomethacin. CONCLUSIONS: These results provide further
      evidence, that ML3000 inhibits 5-LOX as well as COX-1 and COX-2 in vitro and in
      animal experiments. The favourable gastrointestinal (GI) tolerability of the
      compound is believed to be linked to the mechanism of combined 5-LOX and COX-1/2
      inhibition of ML3000.

PMID- 12005205
TI  - Sephadex induces eosinophil migration to the rat and mouse peritoneal cavity:
      involvement of mast cells, LTB4, TNF-alpha, IL-8 and PAF.
AB  - OBJECTIVE AND DESIGN: In this study we investigated the chemotactic mediators
      involved in the Sephadex-induced eosinophil migration into the peritoneal
      cavities of rats and mice, and which resident peritoneal cells release these
      mediators. MATERIALS AND METHODS: Sephadex suspension was injected into the
      peritoneal cavities of rats or mice which were pretreated, or not, with specific
      drugs that inhibit synthesis or production of the inflammatory mediators and
      eosinophil chemotactic activities were observed. To investigate the role of
      resident peritoneal cells as a source of these chemotactic factors, the
      macrophage population was enhanced or the mast cell population was depleted. The
      resident cells were also stimulated, in vitro, with Sephadex and the chemotactic
      activity of the supernatants was determined. RESULTS: Sephadex induced dose and
      time dependent eosinophil migration in rats and mouse, which were inhibited by
      dexamethasone and MK 886. BN 52021 only affected the eosinophil migration into
      the mouse peritoneal cavity. An increase in the macrophage population did not
      alter the eosinophil migration induced by Sephadex in rat or mouse. However, mast
      cell population depletion reduced eosinophil migration in rats, but did not alter
      the migration in mice. Sephadex-stimulated rat mast cells released an eosinophil
      chemotactic factor whose release was inhibited by dexamethasone and MK 886. Anti
      TNF-alpha and anti-IL-8 Abs inhibited the chemotactic activity of the mast cell
      supernatant. CONCLUSION: Sephadex-induced eosinophil migration into the rat
      peritoneal cavity is dependent on mast cells, which release LTB4, TNF-alpha and
      CINC-1. Conversely, Sephadex-induced eosinophil migration into the mouse
      peritoneal cavity is mediated by PAF and LTB4, which are not released from
      resident macrophages or mast cells.

PMID- 12005206
TI  - Effect of rofecoxib on nociception and the serotonin system in the rat brain.
AB  - OBJECTIVE AND DESIGN: The purpose of the present study was to determine whether
      the antinociceptive activity of rofecoxib is mediated, at least in part, through
      changes in the brain serotonergic system. MATERIALS AND SUBJECTS: Male Wistar
      rats weighing 180-200 g (groups of eight) were subjected to the hot-plate and
      formalin tests after rofecoxib treatment. Cortical areas were removed for
      serotonin (5-HT) level, 5-HT2 and mu-receptor evaluation. TREATMENT: Rofecoxib
      was administered orally at doses of 5, 10, 20 and 50 mg/kg for the time course
      evaluation in the hot-plate test (30, 60 and 120 min), and at the dose of 10
      mg/kg for the formalin test and biochemical determinations. METHODS: The tests
      performed were the hot-plate and the formalin assays. HPLC was used to determine
      5-HT levels and radioligand-binding assays were utilized to evaluate the
      characteristics of 5-HT2 and mu-receptors. The data were analysed by ANOVA or
      Student's t test. RESULTS: The lowest active dose of rofecoxib in the hot-plate
      test was 10 mg/kg. The percentage of the maximum possible effect (%MPE) values
      were: control = 1.7+/-3.4; treated 23.4+/-6.5 (p<0.05). The same dose had a
      significant effect on both phases of the formalin test. Pretreatment with p
      chlorophenylalanine (PCPA) significantly decreased the activity of rofecoxib in
      the hot-plate test. Rofecoxib treatment increased serotonin levels and decreased
      the maximum number of 5-HT2 receptors. 5-HT levels (ng/g) were: control = 240.1
      +/- 28.5, rofecoxib = 326.1 +/- 19.9 in the frontal cortex. The characteristics
      of mu-receptors did not change. CONCLUSIONS: These results suggest that rofecoxib
      may exert its therapeutic effect, at least in part, through the central
      serotonergic system. The opioidergic system, on the other hand, seems to be
      unaffected.

PMID- 12005207
TI  - Prophylactic effect of JTE-607 on LPS-induced acute lung injury in rats with CINC
      1 inhibition.
AB  - OBJECTIVE AND DESIGN: JTE-607, a multiple cytokine inhibitor, was evaluated in
      lipopolysaccharide (LPS)-induced acute lung injury in rats in vivo and in vitro.
      MATERIALS AND METHODS: LPS instillation into airways of rats was performed. JTE
      607 at 3-30 mg/kg and dexamethasone at 3 mg/kg were administered intravenously at
      10 min and 0 min for JTE-607, and 60 min for dexamethasone prior to the LPS
      instillation (n = 8). Cytokine-induced neutrophil chemoattractant (CINC)-1 level
      and myeloperoxidase (MPO) activity in lung were measured at 4 h after LPS
      instillation, and at 24 h for lung wet weight measurement and histological study.
      LPS-induced CINC-1 production by rat alveolar macrophages were also measured in
      vitro. RESULTS: JTE-607 and dexamethasone showed a significant reduction of
      increased CINC-1 level and MPO activity in lung after LPS treatment in vivo.
      Increased wet weight was also significantly inhibited. Histological studies
      revealed that JTE-607 and dexamethasone significantly inhibited LPS-induced
      accumulation of peribronchial neutrophils and eosinophils, and perivascular
      edema. JTE-607 and dexamethasone suppressed CfNC-1 synthesis by rat alveolar
      macrophages in vitro with IC50 values of 12.4 microM and 2.3 nM, respectively.
      CONCLUSIONS: These results indicate that JTE-607 has an inhibitory effect on LPS
      induced rat lung inflammation in parallel with CINC-1 reduction. The effect of
      JTE-607 was suggested to be through direct inhibition of CINC-1 production from
      rat alveolar macrophages. JTE-607 may thus be efficacious in cytokine-mediated
      lung inflammation such as acute respiratory distress syndrome.

PMID- 12005208
TI  - New developments in clinical chemistry and laboratory medicine as documented by
      EUROMEDLAB 2001--the 14th IFCC-FESCC European Congress of Clinical Chemistry and
      Laboratory Medicine, Prague, May 26-31, 2001.

PMID- 12005209
TI  - Haptoglobin polymorphism and body iron stores.
AB  - In humans the iron status is influenced by environmental and genetic factors.
      Among them, the genetic polymorphism of the hemoglobin (Hb)-binding plasma
      protein haptoglobin (Hp) has been shown to affect iron turnover. The best known
      biological function of Hp is capture of free Hb in plasma to allow hepatic
      recycling of heme iron and to prevent kidney damage during hemolysis. In healthy
      males, but not in females, the Hp 2-2 phenotype is associated with higher serum
      iron, higher transferrin saturation, and higher ferritin than Hp 1-1 and 2-1.
      Moreover, serum ferritin correlates with monocyte L-ferritin content, which is
      also highest in Hp 2-2 subjects due to endocytosis of multimeric Hb-Hp 2-2
      complexes by the recently identified Hb scavenger receptor CD163 in macrophages.
      This iron delocalization pathway, occurring selectively in Hp 2-2 subjects, has
      important biological and clinical consequences. The Hp polymorphism is related to
      the prevalence and the outcome of various pathological conditions with altered
      iron metabolism such as hemochromatosis, infections, and atherosclerotic vascular
      disease.

PMID- 12005210
TI  - Immunohistochemistry in the evaluation of spermatogenesis and Sertoli cell's
      maturation status.
AB  - An increasing incidence of male infertility has been noted over the past few
      decades. This adds urgency to the need to develop immunohistochemical markers for
      better evaluation of testicular biopsies. We provide evidence that a
      histopathological evaluation performed according to morphological criteria and
      assisted by immunohistochemical staining on consecutive sections enhances the
      sensitivity and accuracy of the diagnosis based on testicular biopsies from
      infertile men.

PMID- 12005211
TI  - Study of therapy resistance in cancer cells with functional proteome analysis.
AB  - Different types of cancer are naturally resistant to many anticancer drugs.
      Additionally, these tumours develop acquired drug resistance, which includes the
      classical multidrug resistance (MDR) accompanied by the synthesis of P
      glycoprotein, a member of the superfamily of ATP-binding cassette (ABC)
      transporters. Furthermore, atypical MDR is mediated by several different, some
      unknown, mechanisms. To overcome chemoresistance problems, antineoplastic drugs
      are often combined with other modes of therapy, e.g. hyperthermia, where good
      response has been reported in several experimental tumour models and in advanced
      cancer patients. The success of this combined anticancer treatment may be limited
      by an increase in chemoresistance and thermoresistance. A model system to study
      resistance phenomena is the use of chemoresistant and thermoresistant cancer cell
      lines. We have established chemoresistant cancer cell lines (gastric and
      pancreatic carcinoma, fibrosarcoma, melanoma) and now thermoresistant cell lines
      derived from gastric and pancreatic carcinoma cells and their counterparts that
      were resistant towards daunorubicin (classical MDR) and mitoxantrone (atypical
      MDR). Using proteomics, in this paper we evaluate the drug resistance of
      chemoresistant melanoma cells (parental cell line MeWo and sublines exhibiting
      drug resistance towards etoposide, cisplatin, fotemustine and vindesine) as a
      paradigm for analysis of drug resistance phenomena. Additionally, we investigate
      heat resistance and the interaction of chemoresistance and thermoresistance to
      identify common pathways using the parental and drug resistant stomach cancer
      cell lines EPG85-257, EPG85-257RNOV, EPG85-257RDB and their thermoresistant
      counterparts. Possible implications of differential protein expression will be
      discussed.

PMID- 12005212
TI  - Proposition of an aging indicator from general health examination in France.
AB  - We present an indicator of aging based on eight quantitative variables, measured
      during the periodical health examination offered by French social security to the
      general population in France. The used sample derived from the population
      examined each year. We selected a reference group of 24,510 adults older than 25
      years (non-smokers, drinking less than 44 g alcohol per day, with body mass index
      less than 35, and not using medication). A multiple regression analysis by gender
      was used to select significant variables to predict age from all quantitative
      variables measured during the health examination. The resulting biological age
      could be calculated from the measured variables and the aging indicator was
      defined as the difference between the calculated age and the chronological age.
      By definition, this indicator is independent of age in the reference population
      and gives an indication of the difference between an individual's status in the
      process of aging and the mean status of people of the same chronological age.
      Associations between this indicator and life style habits such as tobacco and
      alcohol use, and occupational status were observed. A geographical analysis also
      exhibited significant variation over France. Such an indicator can be used at the
      individual level as a pedagogical tool to explain the observed individual health
      status. It is also of interest for the epidemiological studies, where it could
      contribute to a better understanding of the aging process and associated factors.

PMID- 12005213
TI  - Comparison of plasma cardiac troponins T and I in chronically hemodialyzed
      patients in relation to cardiac status and age.
AB  - Cardiac troponins (cTnT and cTnI) are useful tools for risk stratification in
      patients with unstable angina. However, their value in patients with renal
      failure has been questioned. In this study, we determined cTnT and cTnI at 3
      month intervals during 9 months in 97 chronic renal failure (CRF) patients
      treated with hemodialysis. cTnT was measured using a third generation immunoassay
      and cTnI by fluorimetric immunoassay with a detection limit similar to that of
      cTnT (0.01 microg/l). In the renal patients without coronary heart disease (CHD(
      ) group), cTnT was more frequently elevated above cut-off for acute myocardial
      infarction (AMI) (up to 21.6%) than cTnI (no patient). In the absence of CHD,
      cTnT levels were positively correlated to age, and more than half of the CHD(-)
      patients aged over 60 years had cTnT levels above the upper reference limit (URL)
      of 0.04 microg/l (0.059+/-0.042 microg/l). cTnI increased with age in parallel to
      cTnT but mean levels did not exceed the URL of 0.08 microg/l in the CHD(-)
      patients aged over 60 years (0.036+/-0.031 microg/l). In the patients with
      documented cardiac events (CHD(+)) we found higher troponin levels than in the
      CHD(-) patients of the corresponding age, but for cTnl the differences between
      CHD(+) and CHD(-) patients were significant in the patients aged < or =60 years
      only (0.049+/-0.054 vs. 0.019+/-0.018 microg/l, p<0.05). For cTnT, the
      differences between patients with and without coronary events also tended to be
      less important in the eldest patients. There was a significant correlation
      between cTnI and cTnT levels in the CHD(-) and in the CHD(+) groups. Changes in
      the plasma levels of cardiac troponins are common in hemodialysis patients in the
      absence of CHD, and advanced age appears to amplify these changes. The reason
      could be that most hemodialysis patients with advanced age have subclinical
      lesions and demonstrate release characteristics of troponins that compare to
      those in patients with symptomatic coronary events. Therefore, it will be
      important to analyze troponin elevations above the URL or above the cut-off
      concentration for AMI in asymptomatic renal patients in relation to prognosis.

PMID- 12005214
TI  - Medical and economic outcomes of point-of-care testing.
AB  - Point-of-care testing is concerned with the immediacy of response, primarily
      because of the need to act in a life-threatening crisis or to provide counsel in
      the ongoing management of a chronic disease. There are both clinical, operational
      and economic benefits that can accrue from this testing modality which may be
      observed from several perspectives--the patient, the clinician, the healthcare
      provider, the healthcare purchaser and society. Thus point-of-care testing can
      improve the management of chronic diseases such as diabetes, compromised
      coagulation status and epilepsy--both in terms of optimisation of, and compliance
      with, therapy. There are also life-threatening crises that can be averted by
      rapid provision of test results. Each of these scenarios can lead to more
      efficient use of healthcare resources.

PMID- 12005215
TI  - Are laboratory investigations recommended in current medical practice guidelines
      supported by available evidence?
AB  - It has been suggested that evidence-based laboratory medicine (EBLM) could help
      to improve the pertinence and accuracy of medical guidelines. In order to
      demonstrate this, we have used an EBLM approach (i.e. a systematic review) to
      examine three recently published guidelines that gave quite conflicting
      recommendations regarding the use of laboratory variables in the management of
      primary non-small cell lung cancer patients. In recommending the routine
      measurement of serum albumin, and, to a lesser extent, that of serum calcium in
      the pre-therapeutic prognostic evaluation of the advanced disease, the American
      Thoracic Society and the European Respiratory Society were probably correct with
      regard to calcium but perhaps mistaken regarding albumin. Some of the
      recommendations of the European Group on Tumour Markers regarding the usefulness
      of routine measurements of tumour markers (carcinoembryonic antigen (CEA), cancer
      antigen 125 (CA 125), tissue-polypeptide antigen (TPA)) in the pre- and/or post
      therapeutic prognostic evaluation can also be criticised. In addition, the latter
      society as well as the Societe de Pneumologie de Langue Francaise did not even
      try to list laboratory variables, others than tumour markers, that would be
      useful to stratify patients participating in clinical trials (i.e. lactate
      dehydrogenase (LDH), albumin, calcium, blood cell count, etc.), and the
      laboratory variables listed by the two former societies were probably not the
      right ones in this context: in particular LDH and tumour markers (fragments of
      cytokeratin 19 (Cyfra 21-1), tissue-polypeptide-specific antigen (TPS), neuron
      specific enolase (NSE)) were not mentioned. Most, if not all of these
      discrepancies in the current medical practice guidelines might have been avoided
      had an EBLM approach been used by the authors.

PMID- 12005216
TI  - New aspects on angiotensin-converting enzyme: from gene to disease.
AB  - Angiotensin-converting enzyme (ACE) is a well known zinc-metallopeptidase that
      converts angiotensin I to the potent vasoconstrictor angiotensin II and that
      degrades bradykinin, a powerful vasodilator, both for regulation of vascular tone
      and cardiac functions. Other natural substrates of ACE were identified broadening
      the functions of this enzyme within different physiological contexts such as
      neuronal metabolism, hematopoiesis, digestion and reproduction. Synthetic
      substrates were developed for the determination of ACE activity in various
      biological fluids, mostly human plasma, for the diagnosis of sarcoidosis and
      other granulomatous diseases. After the successful use of captopril, the first
      ACE inhibitor in the treatment of hypertension, a number of molecules were
      synthesized and used in the treatment of congestive heart failure and for
      preventing cardiac impairment after myocardial infarction. This class of
      antihypertensive drugs benefited from structural data on carboxypeptidases active
      site, as ACE molecule has not yet been crystallized. In the last two decades ACE
      gene has been cloned that allowed the identification (i) of two isoenzymes, one
      called somatic ACE resulting from gene duplication and primarily expressed in
      endothelial cells, and the other, called germinative or testicular ACE, resulting
      from the transcription in the male reproductive system of a more simple gene,
      (ii) of an hydrophobic C-terminal peptide for membrane-anchoring and specifically
      cleaved by a metalloprotease to release soluble forms of both isoenzymes, and
      (iii) of several allelic polymorphisms, one of them consisting of an
      insertion/deletion (I/D) polymorphism in a short intronic Alu sequence that could
      account for half the variance in plasma ACE level and resulting in a large inter
      individual variability; moreover this I/D polymorphism was proposed as a genetic
      marker for identifying individuals at high risk of ischemic heart disease and of
      anticipating in one individual the efficacy of the antihypertensive therapy,
      although conflicting data arose from the past decade literature. Moreover, ACE
      gene cloning has confirmed the expression of the enzyme in endothelial cell, in
      particular as an ecto-enzyme facing the vascular lumen, but not to the same
      extent with regard to the vascular origin of the cells. Plasma ACE in healthy
      subjects arises essentially from the endothelium. On the other hand, in
      granulomatous diseases where a local stimulation of macrophages leads to an
      abnormal ACE secretion, it can also be found in other biological fluids such as
      cerebrospinal and broncho-alveolar fluids. Low plasma ACE levels result from
      endothelium impairment such as in deep vein thrombosis or in endothelio-toxic
      anticancer therapies. Another cause of low, sometimes undetectable, plasma ACE
      levels is the use of an ACE inhibitor, but this is without any significance with
      regard to its clinical benefits. Albeit molecular cloning has provided a number
      of new details on ACE structure and function, many questions still remain, in
      particular about its tertiary structure including glycosylations, about its
      tissue-specific expression and regulation, and also about the exact significance
      of the I/D polymorphism in cardiovascular pathology including the pharmacogenomic
      field.

PMID- 12005217
TI  - Oxypurines, protein, glucose and the functional state of blood vasculature are
      markers of renal calcium stone-forming processes? Observations in men with
      idiopathic recurrent calcium urolithiasis.
AB  - In idiopathic calcium urolithiasis the relationships between oxypurines,
      accompanying proteins and glucose in urine and plasma, and the associated
      metabolic activity (MA) are unknown. To establish whether MA is related to these
      parameters and to calcium oxalate crystallization, or whether it reflects a
      reaction of metabolism to systemic insults was the major goal of the work. One
      hundred fifty one males were studied in three trials: trial 1 (n=130 patients)
      and trial 2 (n=24 patients) were cross-sectional; trial 3 included 11 patients
      and 14 controls). Mean age was 46 years (trials 1 and 2) and 29 years (trial 3).
      In trial 1 the stratification was based on the median urinary oxypurine
      excretion, in trial 2 on the median plasma oxypurine concentration (below or
      above: Low and High subgroups). No dietary restrictions were imposed, but
      standardized ambulatory laboratory testing was carried out. MA was quantitated by
      a score. Established analytical methods were used, except for oxypurine
      measurement which was done by high performance liquid chromatography. Patients
      with kidney stones tended to be overweight (body mass index >25 kg/(m)2) and to
      have fasting hyperglycemia. In trial 1 severe oxypurinuria, and especially severe
      xanthinuria, was associated with an increase in urinary pH, creatinine clearance,
      proteins, uric acid, malonedialdehyde (indicator of lipid peroxidation), systolic
      blood pressure, and with a decrease in plasma uric acid (synonymous with a
      decrease of antioxidant capacity). Tubular reabsorption of proteins and stone
      forming substances was diminished but MA remained unchanged despite slightly
      increased calcium oxalate crystal growth. In trial 2 high adenosine and xanthine
      coincided with elevated systolic and diastolic blood pressure, high uric acid
      with high urinary malonedialdehyde, high summed oxypurines minus uric acid with
      an increase of diastolic blood pressure, glycemia and MA; urinary nitrate
      (indicator of systemic vasodilation) was unchanged. In trial 3 patients'
      oxypurinemia and proteinuria were normal, but body mass index, glycemia and
      insulinemia were increased. Urinary total protein, albumin and non-albumin
      proteins were positively predicted (multivariate regression analysis) by urinary
      xanthine, glucose and pH (trial 1); MA was positively (trial 3) or negatively
      (trial 2) predicted by urinary total protein. In calcium urolithiasis, a disorder
      of affluence, 1) oxypurinuria and proteinuria and oxypurinemia and MA appear
      causally linked, presumably via oxidant/antioxidant imbalance-induced renal
      tissue damage; 2) urinary proteins may act as inhibitors or promoters of stone
      forming processes; 3) a stone-initiating role of impaired vasodilatation is
      conjectural; 4) overweight, obesity, mild glucosuria and hyperdynamic blood
      circulation are regular signs.

PMID- 12005218
TI  - Long-chain polyunsaturated fatty acids in rat maternal milk, offspring brain and
      peripheral tissues in essential fatty acid deficiency.
AB  - Fatty acid status in humans is usually related to plasma or red blood cell fatty
      acid profiles. The aim of the study was to explore whether a maternal deficiency
      in dietary essential fatty acids would differentially affect lipid fractions in
      several tissues of the offspring, including brain. Female Wistar rats were fed an
      essential fatty acid-deficient diet during 3 months before mating. The fatty acid
      composition of different lipid fractions was examined in maternal milk, and in
      plasma, red blood cells, liver, adipose tissue, cerebral cortex and hippocampus
      of the offspring using thin layer and capillary column gas chromatography. Lipid
      fractions from most tissues of deprived offspring showed a common fatty acid
      profile characterized by elevated 20:3 omega9/20:4 omega6 ratio, and decreased
      docosahexaenoic acid and arachidonic acid. However, arachidonic acid was not
      affected in brain, even though 22:5 omega6 was increased in phospholipids of
      cerebral cortex and hippocampus. The present results demonstrate different
      degrees of resistance to essential fatty acid deficiency in lipid fractions and
      tissues. This suggests a priority distribution of arachidonic acid to
      preferential areas and shows that blood phospholipid fatty acids do not exactly
      reflect brain phospholipid status.

PMID- 12005219
TI  - Simultaneous quantification of sirolimus, everolimus, tacrolimus and cyclosporine
      by liquid chromatography-mass spectrometry (LC-MS).
AB  - We developed a universal liquid chromatography-mass spectrometry (LC-MS) assay
      with automated online extraction to quantify simultaneously the
      immunosuppressants sirolimus, everolimus, tacrolimus, and cyclosporine. Whole
      blood (300 microl) plus 6 microl 32-desmethoxyrapamycin (1 ng/microl) as internal
      standard was treated with 600 microl methanol/0.2 M ZnSO4 (80/20 v/v). After
      vortexing (30 s) and centrifugation (20000 g, 5 min) 50 microl of the supernatant
      were loaded on an extraction column, were washed by 0.35 ml/min water for 3 min
      and, after activation of a column-switching valve, were back-flushed by 0.25
      ml/min methanol/ water (90/10 v/v) onto a C18 analytical column. After 22 min the
      extraction column was washed for 2 min with methanol and for 3 min with water
      before starting the next run. Column temperatures were kept at 33 degrees C.
      Sodium adduct ions [M+Na]+ ions were detected in the selected ion mode. For
      sirolimus, everolimus and tacrolimus the assay was linear from 0.3 to 200
      microg/l and for cyclosporine from 5 to 1000 microg/l (all r2>0.999). Recovery of
      all immunosuppressants and the internal standard was >90% and in general, inter
      day and intraday precision was <10%. The simultaneous quantification of blood
      levels by LC-MS seems to be the method of choice in transplanted patients
      receiving multiple immunosuppressants.

PMID- 12005220
TI  - Pancreatic phospholipase A2 activity in acute pancreatitis: a prognostic marker
      for early identification of patients at risk.
AB  - Remarkably elevated levels of phospholipase A2 (PLA2) are measurable in human
      blood samples in cases of acute pancreatitis. The source of the enzyme was first
      thought to be exclusively the pancreas, but now it is generally accepted that two
      isoenzymes--the pancreatic PLA2, group I, and the extrapancreatic PLA2, group II-
      contribute to the raised activity. In contrast to the group II-PLA2, the
      pancreatic PLA2 is heat-resistant for 1 hour at 60 degrees C. The catalytically
      inactive proenzyme of the pancreatic PLA2 can be activated by trypsin. The aim of
      our study was to evaluate the diagnostic value of PLA2 isoenzyme activity
      measurements to identify patients with severe complications in acute
      pancreatitis. Blood samples from patients suffering from acute pancreatitis were
      analyzed for catalytically active pancreatic PLA2 on day 1 and 2 of
      hospitalization with a modified radiometric Escherichia coli-based PLA2 assay. In
      10 of 41 patients clearly elevated values of catalytically active, heat-resistant
      pancreatic PLA2 (7.2 to 81.2 U/l) were observed. This group of patients was
      characterized by severe complications (necrotizing pancreatitis, shock, sepsis,
      respiratory problems) of which two patients subsequently died. Patients with low
      or undetectable activity (<7 U/l) of pancreatic PLA2 recovered rapidly. According
      to these results the presence of catalytically active pancreatic PLA2 in serum is
      associated with severe complications of acute pancreatitis. In contrast to total
      serum-PLA2, the catalytic concentration of pancreatic PLA2 can serve as a
      prognostic marker in acute pancreatitis.

PMID- 12005221
TI  - Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer:
      comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen
      (CEA).
AB  - Serum carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA) are
      currently employed in clinical practice as markers for breast cancer,
      particularly in the follow-up and therapy monitoring. However, the American
      Society for Clinical Oncology (ASCO) stated in its clinical practice guidelines
      for the use of tumour markers in breast carcinoma that neither CA 15.3 nor CEA
      are recommended for routine use in screening, diagnosis and surveillance after
      primary treatment, or in monitoring response to treatment, because current
      literature data are insufficient. Cytokeratin fragment 21.1 (CYFRA 21.1) assay
      detects a serum fragment of cytokeratin 19 (CK19) and is employed in the
      diagnosis and management of lung cancer, particularly of squamous cell histotype.
      Breast carcinoma has been demonstrated to express CK19 fragments in the primary
      and metastatic lesions and CK19 mRNA is detectable in peripheral blood from
      patients affected by breast cancer. We measured serum markers CYFRA 21.1, CEA and
      CA 15.3 in the sera from 212 females affected by histologically proven breast
      carcinoma. Patients comprised 96 individuals with untreated primary disease (54
      stage I-II, 18 stage III and 24 stage IV), 30 regional (chest-wall and/or lymph
      nodes) relapsing disease and 68 metastatic (haematogenous metastases) relapsing
      disease. Forty-eight patients previously treated by surgery and without any
      evidence of disease were enrolled to evaluate the role of serum markers in the
      monitoring for recurrence of the disease. One hundred healthy age-matched females
      and 65 patients affected by benign mammary gland disease (including 38 patients
      with mastopathy and 27 with fibroadenoma) were enrolled as controls. Serum levels
      of all markers increased from controls to patients affected by breast cancer,
      from stage I-II to stage IV of the breast cancer and from local to advanced
      recurrence. The comparison of diagnostic accuracy in the detection of primary and
      relapsing breast cancer showed no significant differences between markers.
      Univariate and multivariate survival analysis showed a significant statistically
      prognostic value for CA 15.3 and CYFRA 21.1 but not for CEA. However, the factors
      N and M were confirmed to be very strong predictors of the patients' survival.
      Finally, CEA and CYFRA 21.1 detected less recurrences than CA 15.3. In
      conclusion, our data show no significant improvement in the diagnosis, prognostic
      evaluationand follow-up of breast cancer by CYFRA 21.1 and CEA assays compared to
      CA 15.3 assay. Considering the ASCO statement on tumour markers in breast cancer,
      the CYFRA 21.1 assay should not be employed in clinical practice.

PMID- 12005222
TI  - Serum cholesterol levels in neutropenic patients with fever.
AB  - Hypocholesterolemia, which often accompanies infectious diseases has been
      suggested to serve as a prognostic marker in hospitalized patients. Even though
      patients with chemotherapy-induced leukopenia are at high risk of infection and
      mortality, only limited information is available on serum cholesterol levels in
      these patients. We therefore measured serum cholesterol levels in 17 patients
      with hematological malignancies during chemotherapy-induced neutropenia and
      correlated it with clinical outcome. Patients with fever (>38.5 degrees C) showed
      a significant decrease in serum cholesterol levels within 24 hours. Eight days
      after onset of the fever non-survivors had significantly lower serum cholesterol
      levels (median 2.09 mmol/l, range 0.49-2.79, n=6) compared to survivors (median
      3.23 mmol/l, range 1.68-4.86, n=11). Cholesterol levels in survivors returned to
      baseline levels at the time of discharge from the hospital. At the onset of
      fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis
      factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients,
      but only TNF and TNF receptor p75 levels were significantly different in
      survivors and non-survivors. Our data suggest that a decrease in serum
      cholesterol levels is a prognostic marker in neutropenic patients with fever.
      Release of inflammatory cytokines may in part be responsible for
      hypocholesterolemia in these patients.

PMID- 12005223
TI  - Evaluation of two Mg2+-selective electrodes by means of a flow-through device.
AB  - Monitoring the ionized magnesium (Mg2+) concentration in critically ill patients
      can prevent development of serious and potentially fatal complications. The
      analyzers KONE Microlyte 6 (KONE Instruments, Espoo, Finland) and NOVA CRT (NOVA
      Biomedical, Waltham, MA, USA) provide the discontinuous measurement of Mg2+ and
      were evaluated in several studies. It was our objective to integrate the Mg2+
      selective electrodes into a device for continuous on-line measurements. This
      device is suitable not only for research but also for a specific evaluation of
      electrode characteristics. It allowed us to compare the genuine electrodes and
      reference systems independently of their specific analyzers. Precision, accuracy,
      response time, limit of detection, drift and interferences were assessed by
      continuous flow-through measurements and discussed in comparison to the results
      of previous studies. The NOVA electrode proved to be superior regarding accuracy,
      sensitivity and selectivity, especially with respect to calcium. It was
      demonstrated that current commercial serum-like control materials were not
      appropriate for quality control of the assessed Mg2+-electrodes. However, despite
      the fact that the electrodes are commercially used for discontinuous
      measurements, both sensor types can be used for continuous on-line measurements
      in an extracorporeal circulation in a rat model. The NOVA electrode showed
      superior characteristics with this application as well. This study should also be
      understood as a contribution to the development of devices for online analyzers
      used in point-of-care-testing.

PMID- 12005224
TI  - The management of clinical laboratories in Europe: a FESCC survey. Forum of the
      European Societies of Clinical Chemistry and Laboratory Medicine.
AB  - The professional duties of the specialists in clinical chemistry differ from
      country to country in Europe. One of the main goals of the Strategic Plan of the
      Forum of the European Societies of Clinical Chemistry and Laboratory Medicine
      (FESCC; IFCC-Europe) is to promote a high scientific and professional standard in
      the field of clinical chemistry and laboratory medicine in Europe. This can be
      stimulated by the knowledge of the local conditions in each country and by
      striving towards a strong and harmonised position in all the European countries.
      In order to enhance the knowledge of the managerial situation of the specialists
      in clinical chemistry in Europe, FESCC launched a survey in September 2000. This
      survey provides information about the position of the specialists in clinical
      chemistry in the various disciplines in the medical laboratories and in
      hospitals, and about the advisory tasks and the managerial education during the
      post-graduate training in clinical chemistry. Of the 35 FESCC member countries 33
      have participated in the survey (94%). The results show a rather heterogeneous
      situation in Europe caused by the local historical developments, the differences
      in academic background and the relative numbers of private and physicians' office
      laboratories. Large differences exist between the European countries in the
      disciplines of laboratory medicine that are headed by a specialist in clinical
      chemistry. In the different countries the clinical chemistry laboratories are
      headed by specialists in clinical chemistry in between 20% and 100% of the
      laboratories. The haematology, immunology, microbiology, therapeutic drug
      monitoring, molecular biology and haemostasis laboratories and departments of
      blood banking are headed by specialists in clinical chemistry in between 0% and
      100% of the laboratories. The responsibilities for the various managerial tasks
      of the specialists in clinical chemistry show no uniformity in Europe. In the
      majority of the countries the general management, the purchase of equipment and
      reagents and the education of technicians are in >90% the responsibility of the
      specialists in clinical chemistry. In most countries the majority of the
      specialists in clinical chemistry are members of the medical staff of the
      hospitals and have a position equivalent to the position of specialists in other
      medical disciplines. In some countries, however, it only holds true for the
      specialists with a medical background. In 79% of the countries the law regulates
      the profession of the specialists in clinical chemistry and in 60% of the
      countries the law regulates their position in the medical staff of the hospital.
      The advisory tasks to physicians, general practitioners and other users of
      laboratory tests are practised by >90% of the laboratories in 64% of the
      countries. Information is given directly to the patients by >90% of the
      laboratories in 30% of the countries. Only in a few countries laboratories give
      information to the public. The post-graduate training in clinical chemistry
      includes a managerial training in 58% of the countries, the study of information
      technology in 61% of the countries and an economy and/or a business
      administration study in 15% of the countries. In 27% of the countries no
      managerial education forms part of the post-graduate study in clinical chemistry.
      Harmonisation of the managerial aspects of the profession is one of the
      challenges for the European specialists in clinical chemistry. A European
      syllabus for post-graduate training could be helpful.

PMID- 12005225
TI  - Duration processing in children as determined by time reproduction: implications
      for a few seconds temporal window.
AB  - From research carried out over recent years using different experimental
      paradigms, it has become apparent that central information processing is
      temporally segmented into sequential units of a few seconds. This segmentation
      presumably reflects a neuronal process of temporal integration (TI) which
      automatically binds successive events into temporal units. Support for such TI
      comes, for example, from studies on temporal reproduction where standards up to
      approximately 2-3 s are reproduced veridically. Using this paradigm of temporal
      reproduction, we investigated the effect of normal cognitive development of
      sensory modality and of the range of presented standards on TI. Sixty children
      aged 6-7, 9-10 and 13-14 years reproduced visual or auditory standard durations
      ranged from 1 to 5.5 s or from 1 to 3 s. The results showed that durations of
      approximately 2 s were reproduced correctly, whereas those longer than 2.5 s were
      under-reproduced in the three age groups. For standards shorter than 2 s
      substantial age-related differences were revealed: the youngest group displayed
      significant over-reproduction comparing to older subjects. These observations
      indicate that the upper limit for TI is a stable feature across the different age
      groups. Furthermore an age-related modulation within the temporal window of the
      operating TI seems to be linked to cognitive development.

PMID- 12005226
TI  - Does the proportion of associatively related pairs modulate the associative
      priming effect at very brief stimulus-onset asynchronies?
AB  - A number of experiments have shown that the magnitude of the associative priming
      effect increases substantially when there is a high proportion of associatively
      related pairs in the list when the stimulus-onset asynchrony (SOA) between prime
      and target is long (more than 400 ms). In the present series of experiments we
      manipulated the proportion of associatively related pairs when the SOA was very
      brief (less than 200 ms). If processing of a target word is facilitated
      automatically by the prior presentation of a related prime, the occurrence of
      priming should be unaffected by the proportion of related pairs in the list.
      Experiment 1 showed a robust relatedness proportion effect obtained in a double
      lexical decision task. Experiments 2-4 used the masked priming technique at
      several very short SOAs (66, 116, and 166 ms) in lexical decision and naming. The
      results showed a reliable associative priming effect in the two tasks, which did
      not differ as a function of the proportion of related pairs. Finally, Experiment
      5 used unmasked primes at an 83-ms SOA in which the primes remained in view after
      the target presentation. As in Experiments 2-4, the associative effect was not
      modulated by the proportion of associatively related pairs. The implications of
      these results are discussed.

PMID- 12005227
TI  - Motor initiation and execution in patients with conversion paralysis.
AB  - Motor initiation and motor execution in four patients with conversion paralysis
      were investigated in a non-affected motor modality (speech). In line with the
      hypothesis of dissociated control in conversion disorder [Cognit. Neuropsychiatry
      8 (1) (2001) 21] motor initiation, but not response duration, was expected to be
      impaired. The motor initiation times (reaction time: RT) and motor execution
      times (response duration: RD) were compared on four RT-tasks that required the
      production of a verbal response: a simple choice RT-task, a mental letter
      rotation task, and an implicit and an explicit mental hand rotation task. Because
      conversion disorder is expected to primarily involve an impairment in the
      initiation of movement, we expected the following task characteristics to
      uniquely affect RT and not RD: type of instruction (implicit versus explicit
      instructed imagery), angle of rotation, and target arm (affected versus non
      affected arm). The results indeed showed the task characteristics to
      significantly affect the participants' RT and not their RD. It was concluded that
      conversion paralysis is associated with a specific impairment in the explicit
      initiation of processes with a spatial and motor component.

PMID- 12005228
TI  - The perception of closed flat knots and completion by folding.
AB  - The aim of the present research was to study a well-defined set of line drawings
      that have never been analyzed before, and that are perceived as closed flat knots
      (CFKs). These knots are obtained by folding two-dimensional laminae. From this
      study it emerged that the perception of CFKs is always accompanied by a type of
      amodal completion, which had not previously been studied, and which we have
      called "completion by folding". It occurs when three quadrilaterals are so
      arranged that they look like a sheet of paper folded around one of them, partly
      occluded and partly occluding. Two experiments were carried out on this
      phenomenon revealing that a three-level stratification is produced in the
      completion by folding that facilitates unification between occluded figures, even
      when current models do not foresee such a perceptual solution, either because the
      distance between the two figures that become a unit is too big (experiment ) or
      because the slope between the two figures is not favorable (experiment 2). A
      third experiment, which took up the problem of the perception of CFKs, revealed
      the following: (1) Besides the prototype CFK, obtained by the interlacing of a
      rectangular lamina, there is a theoretically infinite class of CFKs. (2) The
      drawing of all the possible closed flat knots involves geometrically precise
      rules. (3) Not all feasible knots with these rules are seen as such. (4) Only the
      knots with characteristics of alignment and regularity are recognized as knots.
      (5) The closed flat knots are seen as the result of a transformation which the
      figure undergoes. This evidence constitutes a remarkable perceptual problem,
      discussed with reference to the recent theories of amodal completion.

PMID- 12005229
TI  - Scale invariance in near space: pointing under influence of context.
AB  - This paper describes the results of a pointing task close to the observer. Unlike
      most research reported in literature, the stimuli were composed of real solid
      objects in an unambiguous context, free of any cue conflict. Moreover, the
      stimuli were either within arm-reach or just beyond arm-reach, thus having strong
      binocular depth cues. Surprisingly, systematic errors up to four times the
      standard deviation were found. These errors depended mainly on the variations in
      context and hardly on egocentric distance. In good first approximation, the
      results were scale invariant. These results are in direct conflict with classic
      theories about visual space. The stimuli were unambiguous real 3-D equivalents of
      the computer-generated stimuli we used in a previous experiment. A comparison of
      the results did not reveal a clear effect of a depth cue conflict between
      accommodation and disparity.

PMID- 12005230
TI  - Endogenous saccades are preceded by shifts of visual attention: evidence from
      cross-saccadic priming effects.
AB  - The present study examines whether endogenous saccades are preceded by shifts of
      attention. Three experiments are reported in which participants were required to
      execute a saccadic eye movement to a certain location and to subsequently
      identify the orientation of a target triangle. Prior to the execution of the
      saccade a prime was presented, which was compatible or incompatible with the
      target. A priming effect (faster responses in the compatible condition than in
      the incompatible condition) occurred only when the prime was presented at the
      saccade destination, and this effect was larger when the prime was presented
      during oculomotor programming than when it was presented prior to oculomotor
      programming. The results indicate that an endogenous shift of attention precedes
      endogenous saccades, providing further support for theories of visual selection
      that assume a tight coupling between attention and saccades.

PMID- 12005231
TI  - Initial characteristics of koi herpesvirus and development of a polymerase chain
      reaction assay to detect the virus in koi, Cyprinus carpio koi.
AB  - Since 1998, episodes of mass mortality have occurred in populations of common
      carp Cyprinus carpio carpio in Israel and in populations of koi Cyprinus carpio
      koi in Israel and the USA. A herpesvirus isolated from infected fish has been
      shown in experimental studies to induce disease and mortality similar to those
      observed in outbreaks at infected farms. Initial characteristics of the virus
      show that it is clearly different from Herpesvirus cyprini (CHV), the most
      commonly known herpesvirus from cyprinid fish. The koi herpesvirus (KHV) has 31
      virion polypeptides. Twelve of the virion polypeptides of KHV have similar
      molecular weights to those of CHV and 10 are similar to those of channel catfish
      virus (CCV). Both virion polypeptide and restriction fragment length polymorphism
      analyses of genomic DNA showed that the first KHV isolates from Israel and the
      USA were identical. In contrast, the genomic DNA restriction fragments clearly
      distinguish KHV from CHV and CCV. A polymerase chain reaction (PCR) assay to
      detect the virus in koi tissues was developed with sequences obtained from 1
      restriction fragment of KHV DNA. The PCR assay effectively detected a 484 base
      pair sequence from KHV but did not amplify genomic DNA from either CHV or CCV.
      The PCR assay detected as little as 1 pg of KHV DNA mixed with 100 ng of host
      DNA. Viral sequences were amplified from koi obtained from field collections and
      from koi that were experimentally exposed to 10(2) TCID50 ml(-1) of KHV via the
      waterborne route. All KHV exposed fish dying of infection between 8 and 10 d post
      exposure or surviving to 14 d post exposure were found to be positive by PCR,
      while unexposed control koi were all negative. The assay also showed the presence
      of KHV DNA in tissues of koi obtained from farms in Israel. The PCR assay should
      assist virus isolation procedures and histologic and electron microscopic
      analyses now commonly used to detect KHV infection. Current studies are examining
      the possibility of using the PCR to detect KHV DNA in live fish and the relative
      sensitivity and specificity of the KHV PCR assay compared with other diagnostic
      tests.

PMID- 12005232
TI  - Binding of haemin by the fish pathogen Photobacterium damselae subsp. piscicida.
AB  - Whole cells of virulent (DI 21 and B 51) and avirulent (ATCC 29690 and EPOY 8803
      II) strains of Photobacterium damselae subsp. piscicida, grown under iron
      supplemented or iron-restricted conditions, were able to bind haemin. Iron
      limitation resulted in an increased binding of haemin by DI 21, B 51 and ATCC
      29690 cells but did not affect the haemin-binding ability of the EPOY 8803-II
      cells. Proteinase K treatment of whole cells markedly reduced the binding of
      haemin, indicating that protein receptors located at the cell surface are
      involved in the binding. This was confirmed by the observation that isolated
      total as well as outer membrane proteins from all the strains, regardless of the
      iron levels of the media, were able to bind haemin, with the outer membranes
      showing the strongest binding. Haemin binding by membrane protein extracts was
      not affected by heat treatment but was almost completely abolished by Proteinase
      K treatment, suggesting the presence of thermostable protein receptors for
      haemin. The capsular polysaccharide also appears to play a minor role in binding
      of haemin. It was concluded that constitutive as well as inducible mechanisms of
      haemin binding occur in P. damselae subsp. piscicida. These mechanisms would rely
      mainly upon the direct interaction between the haemin molecules and surface
      exposed outer membrane protein receptors.

PMID- 12005233
TI  - Development of Myxobolus macrocapsularis (Myxosporea: Myxobolidae) in an
      oligochaete alternate host, Tubifex tubifex.
AB  - The development of Myxobolus macrocapsularis Reuss, 1906, a myxosporean parasite
      of the gills of common bream Abramis brama L., was studied in experimentally
      infected oligochaetes. In 3 experiments uninfected Tubifex tubifex Muller and
      Limnodrilus hoffmeisteri (Claparede) were exposed to mature myxospores of M.
      macrocapsularis. In all experiments, typical triactinospores developed in T.
      tubifex specimens but no infection was found in L. hoffmeisteri. Triactinospores
      were released from oligochaetes 66 to 99 d after initial exposure. At that time
      pansporocysts containing 8 triactinospores were located in the gut epithelium of
      experimental oligochaetes, but free actinosporean stages were also found in the
      gut lumen of the oligochaetes. Each triactinospore had 3 pyriform polar capsules
      and a barrel-shaped sporoplasm with 32 secondary cells. The spore body joined the
      3 caudal projections with a stout style.

PMID- 12005234
TI  - Xenoma formation during microsporidial gill disease of salmonids caused by Loma
      salmonae is affected by host species (Oncorhynchus tshawytscha, O. kisutch, O.
      mykiss) but not by salinity.
AB  - Host species and salinity often affect the development of disease in aquatic
      species. Eighty chinook salmon Oncorhynchus tshawytscha, 80 coho salmon O.
      kisutch and 80 rainbow trout O. mykiss were infected with Loma salmonae. Forty of
      each species were reared in seawater and 40 in freshwater. The mean number of
      xenomas per gill filament was 8 to 33 times greater in chinook salmon than in
      rainbow trout (RBT). Coho salmon had a mean xenoma intensity intermediate to that
      of chinook salmon and RBT. In contrast to the differences between species,
      salinity had no significant effect on xenoma intensity in any of these host
      species. The onset of xenoma formation occurred at Week 5 postexposure (PE) for
      chinook salmon and RBT, and at Week 6 PE for coho salmon. RBT had cleared all
      visible branchial xenomas by Week 9 PE, whereas xenomas persisted in coho and
      chinook salmon at Week 9 PE. Histologically, xenomas were visible in the filament
      arteries of the branchial arch in chinook and coho salmon gills but were absent
      from RBT gills. Fewer xenomas were seen in the central venous sinusoids of RBT
      than in chinook and coho salmon. The lower xenoma intensity, shorter duration of
      infection and pathological characteristics, common to microsporidial gill disease
      in RBT, suggest a degree of resistance to clinical disease that is not seen in
      coho and chinook salmon.

PMID- 12005235
TI  - Ovipleistophora gen. n., a new genus for Pleistophora mirandellae-like
      microsporidia.
AB  - Based on ultrastructural study and molecular analysis, a new genus,
      Ovipleistophora, is established for Pleistophora mirandellae-like microsporidia
      from roach and ruff oocytes. Unlike Pleistophora, Ovipleistophora has a thick
      additional envelope around the meront. This envelope breaks open to release the
      cells into the host cell cytoplasm. The cells, becoming multinuclear sporogonic
      plasmodia, already have a surface coat that transforms into the sporont wall and
      eventually into the sporophorous vesicle wall. The surface coat and its
      transformation differ from those of Pleistophora, but bear some resemblance to
      those of Trachipleistophora. In Trachipleistophora the sporonts, however, do not
      form plasmodia, as they do in Ovipleistophora and Pleistophora. Small subunit
      ribosomal DNA analysis supports the establishment of the new genus and assignment
      of P. mirandellae from 2 different fish hosts to the same species. The same small
      subunit ribosomal DNA analysis lends support for transferring P. ovariae into the
      genus Ovipleistophora.

PMID- 12005236
TI  - Genetic relatedness among Japanese, American and European isolates of viral
      hemorrhagic septicemia virus (VHSV) based on partial G and P genes.
AB  - Molecular virological analyses of 8 Japanese VHSV (viral hemorrhagic septicemia
      virus) isolates from wild and farmed Japanese flounder Paralichthys olivaceus
      were performed to investigate their genetic relatedness to American and European
      isolates of VHSV. Phylogenetic analyses based on the partial nucleotide sequences
      of G and P genes revealed that there are 2 genogroups of VHSV in Japan. The first
      one represented by the Obama25 isolate is closely related to the American
      isolates (Genogroup I) while the other, the KRRV9601 isolate, is closely related
      to the traditional European isolates (Genogroup III). The 2 types of Japanese
      VHSV showed differences in the relative mobility of the G protein and intensity
      of the antibody reaction on the P and M proteins. The Obama25 type of VHSV is
      widely distributed as a native virus in the coastal areas of western Japan and
      has been responsible for the occurrence of VHSV infection in farmed Japanese
      flounder while the KRRV9601 isolate is considered to have been introduced from a
      foreign country.

PMID- 12005237
TI  - Rickettsia-like organism associated with tremor disease and mortality of the
      Chinese mitten crab Eriocheir sinensis.
AB  - We report the discovery of a rickettsia-like organism (RLO) in cultured
      freshwater Chinese mitten crab Eriocheir sinensis. The RLO caused tremor disease
      and was apparently responsible for a mass mortality (30 to 90%) in 2 provinces in
      southeast China. Moribund crabs were investigated from different districts during
      outbreaks in 1999 and 2000. With electron microscopy, 3 different pathogens were
      detected in moribund crabs: a rickettsia-like organism (RLO), virus-like
      particles (VLP) and a microsporidian-like protozoan (MLP). Based on the high
      prevalence, infection intensity and cytopathological signs, the RLO was
      considered to be the probable cause of the high mortality. Both VLP and MLP
      occurred at low prevalences and were considered secondary infections. The RLO was
      0.22 to 0.35 microm in diameter, granular or clavate, bounded by a cell wall and
      membrane, and possessed no nucleus but a nucleoid was present. When dividing,
      RLOs occurred in irregular shapes, such as dumbbells, awls, and crescents. The
      RLOs exhibited a predilection for muscle and connective tissues and were probably
      transported to various tissues and organs by hemocytes.

PMID- 12005238
TI  - Uterine adenocarcinoma with generalised metastasis in a bottlenose dolphin
      Tursiops truncatus from northern Patagonia, Argentina.
AB  - An endometrial adenocarcinoma with areas of squamous differentiation and
      generalised metastasis was observed in a bottlenose dolphin Tursiops truncatus
      stranded in northern Patagonia in July 1997. This is the second report of a
      uterine adenocarcinoma in a free-living cetacean and the first in a Delphinidae.
      This neoplasm likely compromised reproduction for several years. In addition, the
      dolphin presented tattoo-like skin lesions and its digestive tract was infested
      by Anisakis simplex, Pseudoterranova sp., Braunina cordiformis and Corynosoma
      australe.

PMID- 12005239
TI  - Evidence for apoptosis correlated with mortality in the giant black tiger shrimp
      Penaeus monodon infected with yellow head virus.
AB  - Histological, cytochemical and ultrastructural changes in giant black tiger
      shrimp Penaeus monodon were investigated at various time intervals after
      injection with yellow head virus (YHV). Hemocytes, lymphoid organs (LO) and gills
      were the main focus of the study. After injection with YHV, onset of mortality
      varied from 36 h onward. By normal hematoxylin and eosin staining, the 3 tissues
      showed clear and increasing prevalence of nuclear condensation, pyknosis and
      karyorrhexis from approximately 36 h post-injection (p.i.) until death, although
      pathology was evident in the LO as early as 12 h p.i. in some shrimp. By nuclear
      DNA staining with 4',6-diamidino-2-phenylindole (DAPI) and by specific labeling
      of 3'-OH ends of nuclear DNA using a technique called terminal deoxynucleotidyl
      transferase-mediated deoxy-UTP nick-end labeling (TUNEL), cells of the 3 tissues
      showed evidence of chromatin condensation and DNA fragmentation, respectively.
      Both are generally considered to be characteristic of apoptosis. In addition to
      TUNEL labeling, evidence for DNA fragmentation was supported by the appearance of
      approximately 200 base pair DNA ladders at approximately 48 h p.i. in hemocytes
      of YHV-infected but not uninfected shrimp. Transmission electron microscopy (TEM)
      of LO tissue revealed features of apoptosis in tissues of YHV-infected shrimp
      only. These included marginated, condensed and fragmented chromatin without
      concurrent cytoplasmic damage. Histological, cytochemical, ultrastructural and
      biochemical data were consistent with the hypothesis that widespread and
      progressive apoptosis occurred in susceptible shrimp infected with YHV. Although
      no specific tests were carried out to determine whether this purported apoptosis
      was the cause of mortality, moribund shrimp had extensive deterioration of vital
      tissues such as the hemolymph, gills, heart and LO, suggesting that many
      essential bodily functions had been severely compromised. This probably resulted
      in the gross signs of lethargy and weakness seen, and it is reasonable to suggest
      that further, progressive deterioration could have led to the collapse of vital
      functions followed by death.

PMID- 12005240
TI  - Clearing mechanisms of Vibrio vulnificus biotype I in the black tiger shrimp
      Penaeus monodon.
AB  - Vibrio species' infections are a common sequelae to environmental stress or other
      disease processes in shrimp, but the mechanism by which the shrimp eliminate the
      bacteria is poorly understood. In this study, the penetration, fate and the
      clearing of V. vulnificus were investigated in Penaeus monodon. A bacterial
      disease isolate from a shrimp farm was identified as V. vulnificus biotype I.
      Polyclonal antiserum was raised in rabbits against the bacterium and the
      specificity was verified by ELISA and immunoblot against a range of Vibrio spp.
      and other gram-negative bacteria. The bacteria were then administered to P.
      monodon juveniles by injection, immersion and oral intubation. An indirect
      immunoperoxidase technique was employed in a time course study to follow the
      bacteria and bacterial antigens in the tissue of the shrimp. Bacteria were
      cleared by a common route, regardless of the method of administration.
      Observations in immersion challenge were similar to a combination of those for
      oral and injection challenges. With immersion, bacteria entered the shrimp
      through damaged cuticle or via insertion points of cuticular setae. Shortly after
      entry, whole bacterial cells were observed in the haemolymph and connective
      tissue. They were either phagocytosed by haemocytes, or broken down outside host
      cells. Haemocytes containing bacterial cells or antigens (HCB) were observed in
      the connective tissue and haemolymph. HCB accumulated around the hepatopancreas,
      midgut, midgut-caecum, gills, heart and lymphoid organ. Free bacterial antigens
      also accumulated in the heart and lymphoid organ. Bacteria entering through the
      mouth by oral intubation or immersion were broken down so that only soluble or
      very fine particles entered the hepatopancreas. Bacterial antigens passed through
      the hepatopancreas into the haemolymph. Antigens were initially observed in the
      haemolymph sinuses and subsequently accumulated in the heart and lymphoid organ.
      Bacterial antigens were released from the shrimp, initially through the gills and
      subsequently through hepatopancreatic B-cells, branchial podocytes and sub
      cuticular podocytes.

PMID- 12005241
TI  - Analysis of three genetic markers in IgA nephropathy patients from a single
      region.
AB  - BACKGROUND: IgA nephropathy (IgA-N) is the most common glomerular disease.
      Various genetic factors have been suspected to influence the disease, but they
      never have been studied in the same cohort of patients. METHODS: In 125 IgA-N
      biopsy-proven cases, we studied by DNA techniques the allele distribution of 3
      polymorphic loci: the angiotensin-converting enzyme (ACE) gene, the specific HLA
      DQB1 gene and the hs1,2 enhancer of the alpha1 gene of the IgH locus. Patients
      were classified as progressive and non-progressive based on a creatininemia above
      150 microl/ml or/and a deterioration of the clearance greater than 3 ml/min/year.
      We analyzed the influence of the polymorphism on the development and the
      progression of the disease. The control group consisted of 83 heathly subjects.
      RESULTS: The frequency of HLA-DQB1*0602 was decreased in IgA-N patients (3.6% vs
      10.2%, Pc = 0.04, RR = 0.36), suggesting a protective effect of this allele for
      IgA-N. Kaplan-Meyer analysis with the Cox-proportional hazard model revealed a
      shorter time between diagnosis and renal failure in patients with the B allele
      for the al gene hs1,2 enhancer (p = 0.04). ACE polymorphism did not influence the
      development or the progression of the disease. CONCLUSION: Genes controlling the
      immune response, such as HLA DQB1 and the alpha1 transcriptional enhancer gene,
      may influence the development and/or the progression of IgA-N nephropathy.
      Patients who develop an IgA-N nephropathy have a higher risk of severe evolution
      if they have a profile of high IgA humoral responder.

PMID- 12005242
TI  - Plasma bone-specific alkaline phosphatase changes in hemodialysis patients
      treated by alfacalcidol.
AB  - Vitamin D derivatives correct high bone remodeling by decreasing plasma iPTH
      concentration in uremic patients with secondary hyperparathyroidism. However,
      without bone biopsy, plasma iPTH alone might not provide sufficient information
      regarding vitamin D-induced bone changes. Plasma bone-specific alkaline
      phosphatase (bAP) seems more sensitive than iPTH in assessing the degree of bone
      remodeling. We prospectively studied the evolution of iPTH and bAP in 14 adult
      hemodialysis patients treated for 1 year by i.v. alfacalcidol pulses. The mean
      total alfacalcidol dose was 0.08 +/- 0.02 g/kg/week. Ten patients completed the
      study, 2 patients had to be parathyroidectomized before week 24 because of
      hypercalcemia and uncontrolled hyperphosphatemia, and 2 other patients died
      before week 36. Mean iPTH levels diminished from 826 +/- 300 pg/ml (range 507 -
      1,500 pg/ml) at baseline to 436 +/- 371 pg/ml (range 18 - 1,095 pg/ml) after 52
      weeks of treatment (48% of decrease). Only 2 patients normalized plasma iPTH
      levels while 8/10 normalized bAP. Five patients remained with plasma iPTH
      concentrations higher than 5-fold the normal value. In contrast, plasma bAP
      levels declined from 47.6 +/- 32.2 ng/ml (range 15.4 - 130.0 ng/ml) at baseline
      to 17.8 +/- 9.9 ng/ml (range 8.0 +/- 38.0 ng/ml) at week 52 (63% of decrease).
      Bone histomorphometry was available in 6 patients after 15.8 +/- 5.1 months of
      alfacalcidol treatment. None of them met the criteria of adynamic bone disease as
      they had increased bone resorption and marrow bone fibrosis. Bone formation rate
      was normal in 2 patients and unmeasurable in the other 4. Two patients showed
      signs of osteomalacia. In conclusion, alfacalcidol preferentially reduced bone
      formation rate rather than the other histological parameters of secondary
      hyperparathyroidism. It reduced plasma bAP more efficiently than iPTH.

PMID- 12005243
TI  - Effect of biocompatibility of hemodialysis membranes on mortality in acute renal
      failure: a meta-analysis.
AB  - BACKGROUND: The effect of biocompatibility of hemodialysis membranes on mortality
      in acute renal failure (ARF) has been a subject of intense debate, with some, but
      not all studies reporting a lower risk of death among patients with ARF dialyzed
      with biocompatible membranes (BCM) compared to bioincompatible membranes (BICM).
      OBJECTIVES: We performed a meta-analysis of group data extracted from previously
      published studies of controlled clinical trials to assess the impact of BCM on
      the mortality among patients with ARF who required intermittent hemodialysis
      (IHD). METHODS: BCM and BICM were defined as synthetic and cellulose-derived
      membranes (cuprophan and cellulose acetate), respectively. All controlled
      clinical trials comparing the effect of BCM to BICM on clinical outcomes in the
      setting of ARF were included. Original articles as well as abstracts were
      included. Data in Tables, Figures, and text were independently extracted by 2 of
      the authors. Risk ratios (RR) for mortality were combined using the random
      effects model. RESULTS: Seven studies with a total of 722 patients met the
      inclusion criteria. One hundred seventy-two (45%) of 384 patients died in the BCM
      group, compared with 156 (46%) of 338 patients in the BICM group. The RRs for
      mortality ranged from 0.56-1.28. Overall, the pooled RR for mortality was 0.92
      (95% CI = 0.76-1.13) in favor of the BCM group. However, the test for
      heterogeneity in RR among studies was significant (chi2 = 8.6, p < 0.05). One
      study accounted for this significance, and once removed from the model, the RR
      for mortality was 0.94 (95% CI = 0.79-1.12), and the test for heterogeneity among
      studies lost its significance. Subgroup analyses comparing BCM to cuprophan
      membranes revealed that the RR for mortality was 0.82 (95% CI = 0.62 - 1.08) in
      favor of the BCM group, whereas in the subgroup of studies comparing BCM to
      cellulose acetate, the RR for mortality was 1.11 (95% CI = 0.87-1.44) in favor of
      the BCM group. CONCLUSION: This metaanalysis demonstrates that the use of BCM
      does not significantly affect mortality among patients with ARF who require IHD.
      However, subgroup analyses suggest that cellulose acetate membranes may offer a
      survival advantage when compared with synthetic membranes, which, in turn, may be
      more beneficial than cuprophan membranes. Available evidence does not permit a
      recommendation for or against the use of BCM in ARF. Large trials and pooled
      analyses of individual patient-level data will be required to assess sources of
      variability among studies and non-fatal outcomes of ARF.

PMID- 12005244
TI  - Comparison between oscillometric and auscultatory methods of ambulatory blood
      pressure measurement in hemodialysis patients.
AB  - INTRODUCTION: 24-hour ambulatory blood pressure monitoring (ABPM) is commonly
      used in clinical and research practice. Different methods have been used in BP
      recording, cuff-oscillometric or Korotkoff sound, and validation studies during
      ABPM have been performed on general as well as hypertensive populations.
      Hemodialysis (HD) patients have a high percentage of complications, such as
      vascular diseases, and they are subject to hyperkinetic blood flows and abrupt
      body weight changes secondary to HD, which can invalidate BP recording.
      Therefore, we wanted to compare the 2 methods on an HD population. PATIENTS AND
      METHODS: We performed 86 ABPMs on 44 patients (aged 60.8 +/- 17.2 years) by using
      a device capable of the simultaneous recording of oscillometric and auscultatory
      BP (A&D Takeda TM2421). The data obtained with the 2 different ABPM methods have
      been compared, and the differences between auscultatory and oscillometric
      determinations have been analyzed, as presented by Bland and Altman [1986].
      RESULTS: The percentage of valid recordings was significantly higher with the
      oscillometric method than with the auscultatory method (93.6 +/- 11.3% vs. 71.7
      +/- 17.04%, p < 0.001). 24-hour diastolic BP and night-time systolic BP were
      higher when recorded with the oscillometric method (DBP = 75.4 +/- 9.6 mmHg vs.
      71.8 +/- 9.6 mmHg, p < 0.001, asleep SBP = 119.7+/-23.3 mmHg vs. 116.2 +/- 25.0
      mmHg, p < 0.001), and the systolic night/day BP ratio was also higher(0.92 +/-
      0.10vs.0.90 +/- 0.10, p < 0.001). Finally, the BP coefficient of variation
      ((SD/mean BP) x 100) was higher when auscultatory determinations were used (16.1
      +/- 4.6 vs. 14.6 +/- 4.9). The limits of agreement between auscultatory and
      oscillometric BP determinations were for SBP = -6.44; 7.84 and for DBP = -3.66;
      10.86. CONCLUSIONS: Differences between 24-hour oscillometric and auscultatory
      ABPM were reported in HD patients: the diastolic 24-hour and asleep systolic BP
      values and the systolic night/day ratio obtained with the oscillometric method
      were significantly higher. The higher coefficient of variation reported with the
      auscultatory method and the wider limits of agreement suggest that the 2 methods
      do not fully coincide and, in our opinion, the oscillometric method is
      preferable, due to the higher number of 24-hour valid measurements.

PMID- 12005245
TI  - Leukopenia and thrombocytopenia in hemodialysis patients with hepatitis B or C
      virus infection and non-hemodialysis patients with hepatitis cirrhosis.
AB  - AIMS: To investigate the relation of leukopenia and thrombocytopenia in
      hemodialysis (HD) patients with hepatitis C virus (HCV) infection. MATERIALS AND
      METHODS: The study included 86 HD patients with hepatitis B surface antigen
      negative and hepatitis C antibody-negative, 28 HD patients with hepatitis C
      antibody-positive, 22 HD patients with hepatitis B surface antigen-positive, 78
      non-HD patients with hepatitis B-induced liver cirrhosis and 38 non-hemodialysis
      patients with hepatitis C-induced liver cirrhosis. The following parameters were
      checked: anti-HCV, hepatitis B surface antigen, hemoglobin, hematocrit, white
      blood cells, platelets, calcium, phosphate, iron, ferritin, albumin, globulin,
      aspartate transaminase (AST), alanine transaminase (ALT) and C-reactive protein.
      The history of blood transfusions, medications, erythropoietin doses and adequate
      dialysis (KTNV) for 6 consecutive months was also recorded from charts. RESULTS:
      The HD patients with positive serum anti-HCV and non-HD patients with hepatitis B
      or C-induced liver cirrhosis had higher prevalences of leukopenia (39.3%, 43.6%
      and 50% vs. 15.1%; p < 0.001) and thrombocytopenia (67.9%, 89.7% and 81.6% vs.
      34.9%: p < 0.001) than HD patients with serum anti-HCV(-)HbsAg(-). The WBC (4,432
      +/- 1,394, 4,792 +/- 2,263 and 4,624 2,446 vs. 5,590 +/- 1,500/mm3; p < 0.001)
      and platelet counts (140 +/- 45, 80 +/- 50 and 89 +/- 65 vs. 186 +/- 62 x
      10(3)/mm3; p < 0.001) of HD patients with positive serum anti-HCV and non-HD
      patients with hepatitis B- or C-induced cirrhosis were also lower than HD
      patients without anti-HCV antibody. The liver cirrhosis patients had more
      thrombocytopenia than the HD patients with anti-HCV(+). The WBC and platelet
      counts did not vary between HD patients with HbsAg(+) and HD patients with anti
      HCV(-)HBsAg(-). The durations of HD, hepatitis and liver cirrhosis were not
      related to the leukopenia or thrombocytopenia (p > 0.05). CONCLUSIONS: HCV
      infection associated with leukopenia and/or thrombocytopenia in HD patients is as
      common as in non-HD patients with liver cirrhosis. This may be due to the direct
      effect of hemopoiesis rather than the hyperspleenism of liver cirrhosis patients.
      There is a need for further prospective investigation to ascertain the clinical
      significance of leukopenia and thrombocytopenia in HD patients with anti-HCV(+).
      The prevalence of leukopenia and thrombocytopenia was higher in HD patients with
      hepatitis C than in HD patients with hepatitis B and HD patient without
      hepatitis.

PMID- 12005246
TI  - Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels
      and excretion of prostaglandins in stable renal allograft recipients.
AB  - AIMS: Although on account of their nephroprotective effects, ACE inhibitors and
      angiotensin receptor antagonists appear to be advantageous for patients after
      renal transplantation, their use in these patients has been limited up to now.
      This is in part due to the risk of inducing a decrease in the glomerular
      filtration pressure gradient with subsequent impairment of allograft function.
      The aim of the present study was to investigate the effects of ACE inhibitors and
      angiotensin receptor antagonists on renal function, excretion of prostaglandins
      as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8
      week withdrawal phase in pretreated patients. PATIENTS AND METHODS: Sixteen
      patients with stable long-term allograft function undergoing therapy with
      candesartan (group 1) and 16 patients with stable long-term allograft function
      undergoing therapy with perindopril (group 2) were included in the study. Any
      signs of chronic allograft dysfunction were defined as exclusion criteria. Renal
      function, albuminuria, TGF-beta1 plasma levels as well as the excretion of
      thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week
      withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor,
      respectively. Normotension was maintained throughout the study period through
      adjustment of other anti-hypertensive drugs. RESULTS: Creatinine clearance as
      well as TGF-beta1 plasma levels and the excretion of prostaglandins remained
      unchanged after discontinuation of candesartan or perindopril. However, after
      withdrawal of the substances a significant increase in albuminuria was noted in
      both patient groups throughout the observation period. After 8 weeks, median
      albuminuria had increased by 63% in group 1 and by 163% in group 2. CONCLUSIONS:
      We were able to demonstrate that the use of ACE inhibitors and angiotensin
      receptor antagonists in patients after renal transplantation is safe. Favorable
      effects of both substances on albuminuria were detectable in patients who showed
      no signs of chronic allograft dysfunction according to the usual criteria.
      Therefore, a nephroprotective effect of candesartan as well as of perindopril, is
      highly probable in patients after renal transplantation. Further investigations
      regarding routine use in these patients are therefore mandatory.

PMID- 12005247
TI  - Membranoproliferative glomerulonephritis associated with low-grade B cell
      lymphoma presenting in the kidney.
AB  - Low-grade B cell lymphoma of mucosa-associated tissue type (MALToma) rarely may
      involve the kidney. Membranoproliferative glomerulonephritis (MPGN) is an
      uncommon complication of B cell lymphoma and may be related to cryoglobulin
      and/or immunoglobulin synthesis by a secretory B cell clone. We report 2 patients
      with the novel renal biopsy findings of coexistent MALToma and MPGN. Both
      subjects presented with nephrotic proteinuria and renal insufficiency. One
      patient had a serum M protein (IgG K) but neither individual had any other
      clinical or serologic evidence of systemic disease, including hematolymphoid
      malignancy, autoimmune disease, cryoglobulinemia, or hepatitis C viral infection.
      Both renal biopsies demonstrated MPGN type I with immunoglobulin deposits that in
      1 case showed light chain restriction (IgM K). Electron microscopy disclosed
      corresponding glomerular electron dense deposits in subendothelial locations.
      Both biopsies also contained atypical interstitial lymphoid infiltrates
      comprising marginal zone (centro-cyte-like) cells that infiltrated tubules and
      showed extra-capsular extension. Immunostains demonstrated a predominantly B cell
      population that lacked expression of CD5 and cycline D1, and gene rearrangement
      studies confirmed the presence of a monoclonal B cell population in both cases.
      These findings indicate that low-grade B cell lymphoma in the kidney may be an
      unexpected finding in patients with nephrotic syndrome related to MPGN.
      Immunophenotypic and gene rearrangement studies are important ancillary tools for
      the evaluation of atypical lymphoid infiltrates in kidney biopsies.

PMID- 12005248
TI  - Carbamazepine-induced acute granulomatous interstitial nephritis.
AB  - A 79-year-old man, newly started on carbamazepine, presented with rash,
      eosinophilia and liver dysfunction progressing to acute renal failure despite
      discontinuation of the anti-epileptic agent. Percutaneous renal biopsy revealed
      acute granulomatous interstitial nephritis, which responded successfully to high
      dose oral steroid therapy.

PMID- 12005249
TI  - Retroperitoneal fibrosis: a case report of spontaneous resolution.
AB  - AIM: The purpose of this case report is to document an occurrence of spontaneous
      resolution of idiopathic retroperitoneal fibrosis and to review the investigation
      and management of this unusual condition. MATERIALS AND METHODS: A detailed case
      summary of a patient with retroperitoneal fibrosis is presented. Current
      citations in Index medicus from the English-speaking literature of relevance to
      the topic were reviewed. CONCLUSIONS: In this patient who refused open surgical
      intervention, bilateral stent placement allowed stabilization of renal function.
      CT-guided biopsy did not reveal malignancy. Serial CT imaging demonstrated
      gradual disappearance of the retroperitoneal mass. From the literature review,
      spontaneous resolution of this condition appears to be a rare phenomenon.
      Although often utilized, CT-guided biopsy may fail to exclude the presence of
      malignancy. Open surgical biopsy of the retroperitoneal mass and ureterolysis
      remain the standard of care for operative candidates. Establishing renal drainage
      and considering a trial of steroids or surveillance may be an option in carefully
      selected individuals.

PMID- 12005250
TI  - Unilateral renal cystic disease--report of one case and review of literature.
AB  - Clinical presentation of unilateral renal cystic disease (URCD) is characterized
      by multiple simple cysts in only 1 kidney. Involvement of other intra-abdominal
      organs is not found. Renal function is usually preserved despite the existence of
      multiple cysts. No genetic background can be delineated up to the present. We
      present 1 patient with URCD, who was evaluated for his right flank pain.
      Urinalysis and biochemical tests showed normal renal function (BUN 5.03 mmol/l,
      creatinine 110.5 micromol/l). Ultrasonographic examination was done and it
      revealed 2 right renal stones. Furthermore, multiple renal cysts over the juxta
      medullary area were noted. His left kidney was intact. Computed tomography (CT)
      of both kidneys confirmed this finding. 99mTc-DTPA renal scan showed that the
      glomerular filtration rate of both kidneys was not significantly different. There
      was no family history of renal diseases. His parents, grandparents and siblings
      were examined for possible kidney lesions, but none of them had any renal cystic
      lesion. This patient was followed for only a relatively short period of time (3
      years) and his renal function did not deteriorate. Follow-up image studies with
      sonography and CT were not different from the previous ones.

PMID- 12005251
TI  - Relationship between urea reduction ratio (URR) and KtN in hemodialysis.

PMID- 12005252
TI  - Intracranial neurothekeoma--a rare parenchymal nerve sheath myxoma of the middle
      cranial fossa.
AB  - Neurothekeomas are rare, benign nerve sheath tumors, usually arising from
      cutaneous nerves in the head and neck region. So far, only 4 cases of the
      intracranial counterpart have been reported and these were located in the
      posterior fossa, sellar and parasellar region. We report here the first case of
      neurothekeoma located deep inside the brain parenchyma. Histologically, the tumor
      had lobular appearance with bland morphology in spite of cellular pleomorphism,
      myxoid background and variable S-100 positivity, characteristics of
      neurothekeomas. The schwannian origin was further confirmed ultrastructurally by
      demonstrating basal lamina and Luse bodies. Because of its benign nature, the
      lesion does not need postoperative radiotherapy. Histogenesis of neurothekeoma
      arising in the parenchyma remains enigmatic. The probable cell of origin could be
      the Schwann cell or perineurial cell of the nerve twigs around the blood vessels
      or by extreme differentiation of the precursor cell resting in a suitable
      microenvironment to the schwannian phenotype.

PMID- 12005253
TI  - The expression of cell cycle regulatory proteins in oligodendroglial tumors.
AB  - Oligodendroglial tumors are mainly classified histologically into 2 types of
      tumors--oligodendrogliomas and oligoastrocytomas--whether the tumor includes
      astrocytic component or not, and these are, respectively, divided histologically
      into 2 different malignant groups, low-grade (WHO grade II) and high-grade or
      anaplastic (WHO grade III). In this study, we investigated the expression of the
      cell cycle-related proteins and analyzed the relationship between the labeling
      index (LI: the percentage of positive nuclei) of these proteins and 2
      histopathological phenotypes, grade and prognosis. Forty-four specimens were
      examined, including 11 oligodendorogliomas (0), 5 oligoastrocytomas (OA), 18
      anaplastic oligodendrogliomas (aO) and 10 anaplastic oligoastrocytomas (aOA),
      according to the WHO classification. Of these, 19 specimens were obtained from
      recurrent tumors of 8 cases. The mean LI of all the investigated proteins between
      O and OA, and aO and aOA showed no significant differences. The mean MIB-1 LI,
      pRb LI, p53 LI and p14 LI of GIII were significantly higher than GII, while the
      mean p27 LI of GIII was significantly lower than GII. In the recurrent cases, we
      noted correlations between the disease-free period and MIB-1 LI (inverse), p27 LI
      and p14 (inverse). Significant correlations were noted between MIB-1 LI and pRb
      LI, MIB-1 LI and cycD1 LI, MIB-1 LI and p27 LI (inverse), pRb LI and cycD1 LI,
      cycD1 LI and cdk4 LI and pRb LI and p27 LI (inverse) in the pRb/cycD1-cdk4/p27
      pathway, and between MIB-1 LI and p53 LI, MIB-1 LI and p14 LI, p53 LI and p14 LI,
      p53 LI and MDM2 LI and MDM2 LI and p14 LI in the p53/MDM2/p14 pathway. In
      conclusion, both pRb/cycD1-cdk4/p27 and p53/N4DM2/p14 pathways correlate with
      malignant progression, and MIB-1 LI, pRb LI, p27 LI, p53 LI and p14 LI reflect
      the histopathological malignancy of oligodendroglial tumors. MIB-1 LI, pRb LI and
      p27 LI are especially useful as indicators of malignancy of oligodendroglial
      tumors.

PMID- 12005254
TI  - Nasal glioma or nasal glial heterotopia? Morphological, immunohistochemical and
      ultrastructural study of two cases.
AB  - The term nasal glioma has been used to describe a congenital benign tumor of the
      nasal region containing neural tissue. The nature of these lesions remains open
      to controversy, because of the different locations of the heterotopic neural
      tissue involved, the deficient development of the bony structures and the
      persistence or not of the structural relations with the central nervous system.
      More recent terms define these lesions as ectopic nervous tissue. A clinical,
      morphological, ultrastructural and immunohistochemical study is made of two cases
      of nasal glioma, one associated with agenesis of the corpus callosum. In this
      case, the mother had been treated with clomiphene. In such cases, morphological
      and immunohistochemical findings support that "nasal glioma" remain valid as a
      descriptive term defining a congenital benign tumor composed of heterotopic
      neural tissue within the nasal region and covered by skin, that may recur
      following incomplete surgical resection.

PMID- 12005255
TI  - MERRF/MELAS overlap syndrome in a family with A3243G mtDNA mutation.
AB  - Four members of a family were found to carry the A3243G mtDNA mutation. Clinical
      features varied from typical MELAS to myoclonic epilepsy to simple deafness
      without neurological signs. Several other members of the family had symptoms
      consistent with a mitochondrial disease. Muscle biopsy in 3 of the 4 patients
      showed the most prominent mitochondrial alterations with partial deficiency of
      cytochrome c oxidase in the case with the mildest phenotype. Mitochondrial DNA
      analysis detected a variable percentage of A3243G mutation, roughly correlating
      with the phenotype. The interesting feature of the family lies in the great
      intrafamilial variability of the severity of clinical expression, encompassing
      MELAS and MERRF features, associated with the A3243G mtDNA mutation. A search for
      the most common mtDNA mutations is recommended in all patients featuring
      incomplete MELAS or MERRF syndromes and in all familial cases presenting minimal
      clinical signs.

PMID- 12005256
TI  - Chorea-acanthocytosis: neuropathology of brain and peripheral nerve.
AB  - We report the neuropathological data from a familial case of chorea
      acanthocytosis with central and peripheral nervous system involvement. At the age
      of 34, the patient underwent a peripheral nerve biopsy which was analyzed by
      light- and electron microscopy. These studies showed a selective reduction in the
      large diameter myelinated fibre population, with several clusters of
      regeneration. Remyelinating fibers surrounded by flattened Schwann cell processes
      were also present. The patient died at the age of 44, and post-mortem macroscopic
      examination of the brain showed marked atrophy of the caudate. Histological
      examination of paraffin sections showed almost complete depletion of neurons in
      the caudate, with severe astrocytic gliosis. The putamen and pallidum were
      slightly less severely depleted of neurons, but with marked astrocytic gliosis.
      Diffuse mild gliosis was also evidenced, by immunohistochemistry with anti-GFAP,
      in the thalamus and subcortical white matter.

PMID- 12005257
TI  - Clinicopathological study of Rathke's cleft cysts.
AB  - The clinical, radiological and pathological characteristics of Rathke's cleft
      cyst are analyzed and compared with those of ciliated and goblet cell
      craniopharyngioma (a subset of papillary craniopharyngioma) to clarify the
      clinicopathological differences between these conditions. We analyzed 42 patients
      with Rathke's cleft cyst and 3 patients with ciliated and goblet cell
      craniopharyngioma. Cyst contents and MRI findings of the cyst generally reflected
      changing pathology of Rathke's cleft cyst. Turbid and less viscous cyst content
      and heterogeneous T1 and/or T2 signals on MRI sometimes represented predominance
      of squamous epithelium in the cyst wall. Pathological study disclosed smooth
      transition from ciliated columnar epithelium typical for Rathke's cleft cyst, via
      ciliated squamous epithelium, to squamous epithelium typical for
      craniopharyngioma in the same patients. Ki-67 immunostaining disclosed that the
      proliferative index of squamous epithelium of Rathke's cleft cyst is
      significantly higher than that of simple or pseudostratified epithelium of
      Rathke's cleft cyst (p < 0.05). In conclusion, our extensive study on Rathke's
      cleft cyst revealed that the high possibility of progression from Rathke's cleft
      cyst, in which either the cyst content or cyst wall are atypical or squamous
      epithelium is predominant, compared to ciliated and goblet cell craniopharyngioma
      and again to papillary craniopharyngioma.

PMID- 12005258
TI  - Role of hypothalamic neuropeptide Y (NPY) in the change of feeding behavior
      induced by repeated treatment of amphetamine.
AB  - Neuropeptide Y (NPY), an orexigenic peptide, is involved in the control of food
      intake. Repeated administration of amphetamine (AMPH), an anorectic agent,
      results in an anorectic effect on day 1 and a tolerant anorectic effect on the
      followings. In an attempt to know the role of hypothalamic NPY in these effects
      of AMPH, contents of hypothalamic NPY were determined by radioimmunoassay at
      first. In AMPH-treated groups, the contents of hypothalamic NPY decreased rapidly
      on day 1 but restored gradually to the normal level on the following days as
      observed in repeated AMPH. An involvement of hypothalamic NPY in the feeding
      change of repeated AMPH can thus be considered. Moreover, daily injection of NPY
      antisense oligonucleotide into brain (10 microg/10 microl/day, i.c.v.) to inhibit
      the gene expression of hypothalamic NPY were performed at 1 hour before daily 2
      mg/kg AMPH. The reversion of food intake from the anorectic level to the normal
      level (tolerant anorexia) was abolished by this antisense pretreatment. It is
      suggested that hypothalamic NPY may play a role in the change of feeding behavior
      induced by repeated AMPH administration.

PMID- 12005259
TI  - Regulation of pro-inflammatory cytokine expression by curcumin in hyaline
      membrane disease (HMD).
AB  - Persistent expression of pro-inflammatory cytokines is believed to play a major
      role in the pathogenesis of chronic lung disease (CLD) in premature infants.
      Inhibition of pro-inflammatory cytokine production in the lungs of preterm
      newborns may result in the attenuation of CLD. Curcumin is a naturally occurring
      phenolic compound derived from the food spice tumeric with broad based in vitro
      anti-inflammatory properties. In this study lung inflammatory cells from preterm
      newborns at risk for the development of CLD were derived via modified broncho
      alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml).
      Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro
      inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the
      culture supernatants 12 hours post culture. For control, adult peripheral blood
      mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal
      lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory
      cytokines in response to LPS. Curcumin produced significant inhibition of IL
      1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung
      inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was
      significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin
      inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by
      lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of
      these cytokines are developmentally intact and functional in premature infants.
      Curcumin may be effective as a therapeutic agent in the attenuation of CLD.

PMID- 12005260
TI  - Effects of six diterpenes on macrophage eicosanoid biosynthesis.
AB  - Six diterpenes (three clerodanes, two abietanes and one rosane) were tested for
      interactions with the cyclooxygenase and 5-lipoxygenase pathways of arachidonate
      metabolism and for effects of nitric oxide production. Two abietane diterpenes,
      aethiopinone and 11,12-dihydroxy-6-oxo-8,11,13-abietatriene and the rosane
      lagascatriol showed a remarkable effect on COX-1 pathway of PGE2 release in
      calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter
      diterpenes showed inhibition on COX-2 pathway of PGE2 release in E. coli LPS
      stimulated peritoneal macrophages. In addition, all compounds assayed were
      inhibitors of LTC4 release with IC50 < or = 10 microM. Clerodane diterpenes were
      inactive in COX assay. None of the diterpenes assayed, except 11,12-dihydroxy-6
      oxo-8,11,13-abietatriene, affected NO production. The results obtained suggest
      that the cellular mechanisms of action of some of these substances may involve
      inhibition of cyclooxygenase/lipoxygenase pathways and nitric oxide production.

PMID- 12005261
TI  - Evidence for the expression of cyclooxygenase-2 enzyme in periodontitis.
AB  - We investigated the role of the inducible isoform of cyclooxygenase (COX-2) in a
      rat model of periodontitis using a selective COX-2 inhibitor NS-398.
      Periodontitis was produced by a silk ligature placed around the lower left 1st
      molar. Animals were treated with NS-398 (3 mg kg(-1) i.p., 2 times per day for 7
      days) or vehicle. At Day 8, the gingivomucosal tissues encircling the mandibular
      1st molars were removed on both sides for COX-2 immunohistochemistry, measurement
      of plasma extravasation by the Evans blue technique, and alveolar bone loss by
      videomicroscopy. Immunohistochemical analysis revealed numerous strongly COX-2
      positive cells in the subepithelial tissues in the ligated side and only a few
      COX-2-reactive cells in the contralateral (control) side. Ligation significantly
      increased Evans blue extravasation in the gingivomucosal tissue and alveolar bone
      destruction compared to the control side. NS-398 treatment significantly reduced
      the plasma extravasation and alveolar bone resorption of the ligated side
      compared to vehicle administration. The present results suggest that COX-2 is
      induced by periodontitis, and plays an important role in gingival inflammation
      and alveolar bone destruction. In a previous study (Br J Pharmacol 1998;123:353
      60) we found the expression of the inducible isoform of nitric oxide synthase in
      this model. Therefore, based on our own data and the literature, we propose that
      selective inhibition of these inducible enzymes might be a basis for adjunctive
      therapy, or new therapeutic approaches in periodontitis.

PMID- 12005262
TI  - Phagocytosis in vitro of polyethylene glycol-modified liposome-encapsulated
      hemoglobin by human peripheral blood monocytes plus macrophages through scavenger
      receptors.
AB  - Liposome-encapsulated hemoglobin (LEH), a candidate for red blood cell
      substitute, is cleared from circulation primarily by the phagocytic system, most
      likely after opsonization of the vesicles by immunoproteins, particularly
      complement components. Although modification of LEH by polyethylene glycol (PEG)
      derivatives prolongs its half-life by blocking the opsonization, the half-life is
      still short as compared with that of red blood cell components. Therefore, this
      study was performed to elucidate the opsonin-independent mechanisms that regulate
      phagocytosis of Neo Red Cell (NRC), a PEG-modified LEH, in culture. PKH67 was
      used as a fluorescence marker, allowing the quantitation of the phagocytosis of
      NRC by peripheral blood monocytes plus macrophages. The phagocytosis of PKH67
      labeled NRC was inhibited by the addition of an excess of unlabeled NRC,
      indicating that the phagocytosis of PKH67-labeled NRC is specific to NRC, but not
      to PKH67. The phagocytosis of NRC was blocked about 70% by anti-CD14, 60% by anti
      CD36 and 30% by anti-CD51/61 (vitronectin receptor, alpha(v)beta3). These results
      provided evidence of an opsonin-independent pathway for the phagocytosis of PEG
      modified LEH.

PMID- 12005263
TI  - Sympathetic and parasympathetic regulation of cystatin S gene expression.
AB  - The autonomic nervous system plays a regulatory role in the differentiation and
      growth of salivary glands, and in the expression of salivary specific genes.
      Cystatin S, a member of the evolutionarily conserved family 2 of the cysteine
      proteinase inhibitor superfamily, expressed in submandibular and parotid glands
      of rats during development, can be induced in adults by the beta-adrenergic
      agonist isopreterenol (IPR). It was shown previously that unilateral
      sympathectomy or bilateral parasympathectomy reduces IPR-induced cystatin S
      expression. The present experiments demonstrate that IPR-induced cystatin S gene
      expression in submandibular glands is reduced as early as 3 days post bilateral
      denervation of both branches of the autonomic nervous system. The reduction is
      nearly equal to that of either sympathectomy or parasympathectomy alone,
      suggesting that factor(s) in both sympathetic and parasympathetic fibers are
      simultaneously required for IPR-induced cystatin S gene expression.

PMID- 12005264
TI  - Brefeldin A inhibits osteoclastic bone resorption through induction of apoptosis.
AB  - Brefeldin A (BFA), a fungal metabolite with a macrocyclic lactone structure, has
      been developed for the treatment of cancer, and its major biological activity is
      the inhibition of intracellular protein transport from the endoplasmic reticulum
      to the cis-Golgi apparatus. In this study, we investigated the effect of BFA on
      osteoclastic pit formation in vitro. BFA reduced pit formation in a concentration
      dependent manner, and the IC50 values on the pit number and the pit volume were
      11.3 +/- 2.2 and 13.3 +/- 2.0 nM, respectively. In parallel with the inhibitory
      effect on pit formation, BFA also reduced the cell viability of osteoclasts
      enriched bone cells with an IC50 value of 13.9 +/- 2.2 nM. These results suggest
      that the inhibition of bone resorption by BFA is caused by the induction of
      osteoclast cell death. BFA at a concentration of 100 nM induced DNA fragmentation
      in purified osteoclasts, assessed by the terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling and DNA ladder formation, demonstrating that BFA
      induces cell death of osteoclasts in an apoptotic manner. In addition, the
      accumulation of p53 proteins to the nuclei was observed in the osteoclasts
      treated with 100 nM BFA. These results, taken together, suggest that BFA inhibits
      osteoclastic bone resorption by inducing apoptosis in osteoclasts through a p53
      dependent mechanism.

PMID- 12005265
TI  - The time course study of osteoinduction by bone morphogenetic protein-2 via
      adenoviral vector.
AB  - We evaluated the time course of osteoinduction by an adenoviral vector, AxCAOBMP
      2, in normal rats (Group I) and 2 immunosuppressed groups (Groups II and III).
      Immunosuppression was induced by 125 mg/kg of cyclophosphamide injected
      intraperitoneally the day before vector injection. Groups I and III received a
      high dose of AxCAOBMP-2 (25 microl; 8.75 x 10(8) pfu) and Group II a low dose (5
      microl; 1.75 x 10(8) pfu). Each dose of AxCAOBMP-2 was injected into the right
      calf muscle of rats. On days 7, 14 and 21 postinjection, the osteoinducive
      activity in each group was investigated radiologically, histologically,
      immunohistochemically and biochemically. Osteoinduction was observed only in
      Groups II and III on days 14 and 21. The activity of osteoinduction in Group III
      was higher than that in Group II. There was little difference in the expression
      of LacZ between Groups I and III on day 3. However, there was a marked difference
      in BMP-2 protein expression between Groups I and III on day 7 postinjection. We
      speculated that the reason for this was that most of the infected cells were
      eliminated by the immune system of the host from days 3 to 7. These results
      suggest that gene therapy with AxCAOBMP-2 under transient immunosuppression may
      be useful for bone reconstruction.

PMID- 12005266
TI  - Effects of arachidonic acid and cyclo (his-pro) on zinc transport across small
      intestine and muscle tissues.
AB  - Previously we have shown that arachidonic acid (AA) plus zinc or cyclo (his-pro)
      (CHP) plus zinc improve clinical signs of diabetes in streptozotocin-induced
      diabetic rats. Since streptozotocin destroys pancreatic beta-cells, we
      hypothesize that the effect of either AA or CHP, plus zinc on glucose metabolism
      is via mobilization of intracellular zinc which in turn stimulates glucose uptake
      by peripheral tissues. We now report the relationship between zinc and AA and
      between zinc and CHP in controlling zinc influx and efflux across hindlimb muscle
      cells isolated from three-month old rats. Although CHP increased muscle zinc
      influx in a dose-dependent manner, AA was not effective. However, AA was more
      effective in stimulating zinc efflux than CHP. We have previously demonstrated
      that AA stimulates intestinal zinc uptake and absorption, and now present
      evidence that CHP also influences intestinal zinc transport. These results
      suggest that both AA and CHP affect glucose uptake in muscle cells via
      stimulating intestinal zinc absorption and muscle cell zinc flux.

PMID- 12005267
TI  - GABA(B) receptor agonist baclofen attenuates the development and expression of d
      methamphetamine-induced place preference in rats.
AB  - The present study investigated the effect of systemic administration of the
      GABA(B) receptor agonist, baclofen, on the development and expression of d
      methamphetamine (d-MA)-induced place preference in male Wistar rats. Using a
      biased and 8-day schedule of conditioning, it was found that administration of d
      MA (0.5 mg/kg, i.p.) produced significant place preference. The administration of
      baclofen (2.5 and 5.0 mg/kg, i.p.) 30 min prior to the exposure to d-MA
      attenuated the development of d-MA-induced place preference (p<0.05). In
      addition, when it was acutely administered 30 min prior to the testing session of
      an already established d-MA place preference, baclofen (1.25-5.0 mg/kg, i.p.)
      attenuated the expression of this conditioned response in a dose-dependent
      manner. These results showed that baclofen suppressed the rewarding effect
      produced by d-MA and may be potentially effective in the treatment of
      methamphetamine dependence and craving.

PMID- 12005268
TI  - Purification of allivin, a novel antifungal protein from bulbs of the round
      cloved garlic.
AB  - A novel antifungal protein, designated allivin, was isolated from bulbs of the
      round-cloved garlic Allium sativum var. round clove with a procedure involving
      ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi
      gel blue gel, ion exchange chromatography on CM-Sepharose and FPLC-gel filtration
      on Superdex 75. Allivin possessed an N-terminal sequence demonstrating very
      little similarity to sequences of Allium sativum chitinases and ribosome
      inactivating proteins. Allivin exhibited a molecular weight of 13 kDa in gel
      filtration and SDS-polyacrylamide gel electrophoresis. It displayed antifungal
      activity against Botrytis cinerea, Mycosphaerella arachidicola and Physalospora
      piricola. It inhibited translation in a cell-free rabbit reticulocyte system with
      an IC50 of 1.6 microM.

PMID- 12005269
TI  - Is there a preferred triptan?

PMID- 12005270
TI  - Treatment of migraine with rizatriptan: when to take the medication.
AB  - OBJECTIVE: To assess, in the setting of routine clinical practice, rizatriptan's
      effectiveness in treating acute migraine at its onset versus in a later phase of
      the attack. BACKGROUND: Although the efficacy and tolerability of rizatriptan
      have been well documented in clinical trials, no information is available about
      the impact of the timing of medication use on clinical outcome. METHODS:
      Migraineurs were enrolled in a prospective study and treated with rizatriptan 10
      mg for two migraine attacks. Patients reported how they used the medication and
      treatment outcomes via an interactive voice response system. Outcome variables
      assessed included: time to onset of headache relief, headache severity 2 hours
      postdose and whether or not patients became largely symptoms-free (including
      associated symptoms), and when they were able to resume normal activities.
      Episodes in which patients took rizatriptan immediately after experiencing
      headache were designated "early use" and those in which patients delayed
      treatment until their headaches evolved to become moderate or severe were
      designated as "delayed use." Generalized estimating equations were used to assess
      the impact of early drug use and to control for age, gender, drug formulation,
      use of other migraine prescription medications before taking rizatriptan, attack
      sequence, migraine attack frequency, and recent migraine severity. RESULTS: A
      total of 1919 migraineurs with 3450 migraine attack episodes were evaluated, of
      which 1369 episodes were early use and 2081 delayed use. Compared to delayed-use
      episodes, episodes wherein patients took rizatriptan early were 1.33 times more
      likely to be characterized by onset of headache relief within 30 minutes
      posttreatment (95% confidence interval [CI], 1.11 to 1.60), 1.32 times more
      likely to result in a largely symptom-free state (95% CI, 1.12 to 1.57), and 1.34
      times more likely to be associated with a return to normal activities (95% CI,
      1.13 to 1.58) within 1 hour posttreatment. No significant difference between
      early-use and delayed-use episodes was observed with respect to the likelihood of
      there being no or mild headache 2 hours posttreatment (odds ratio, 1.05; 95% CI,
      0.90 to 1.24). CONCLUSIONS: Whether taken at headache onset or later in the
      attack, rizatriptan was equally effective in relieving acute migraine headache by
      2 hours postdose. Taking rizatriptan at the onset of headache was associated with
      more rapid relief of headache and reversal of functional disability.

PMID- 12005271
TI  - Almotriptan increases sustained pain-free outcomes in acute migraine: results
      from three controlled clinical trials.
AB  - OBJECTIVE: Evaluate the effect of almotriptan on sustained pain-free outcome in
      patients with acute migraine. METHODS: Three randomized, double-blind, placebo
      controlled trials of almotriptan for the treatment of acute migraine were
      examined. Two trials evaluated almotriptan 6.25 mg and 12.5 mg, and the third
      evaluated almotriptan 12.5 mg and sumatriptan 100 mg. Patients aged 18 to 65
      years were instructed to take 1 dose of study medication at the onset of a
      moderate-to-severe migraine headache. A second dose was allowed for relapse.
      Sustained pain-free was defined as a decrease in pain severity from moderate or
      severe at baseline to no pain at 2 hours postdose and without relapse or the use
      of escape medication between 2 and 24 hours. RESULTS: A total of 1791 adult
      migraine sufferers were studied. The proportion of patients achieving a sustained
      pain-free state was significantly (P<.05) higher in the almotriptan 6.25-mg
      (21.7% to 22.5%) and 12.5-mg (24.6% to 27.6%) groups than in the placebo group
      (7.5% to 12.1%). The proportion of patients achieving a sustained pain-free state
      was comparable between almotriptan 12.5 mg (24.6%) and sumatriptan 100 mg (28.5%)
      and significantly (P<.05) greater than with placebo (12.1%). Among patients with
      severe baseline pain, a sustained pain-free state was achieved in significantly
      more patients (P<.05) with almotriptan 12.5 mg (17.3% to 20.9%) than with placebo
      (3.1% to 3.2%). Among those with moderate baseline pain, a sustained pain-free
      state was achieved in significantly more patients (P<.01) with almotriptan 12.5
      mg (31.3% to 32.0%) than with placebo (10.2% to 16.1%). CONCLUSIONS: Almotriptan
      12.5 mg is significantly better than placebo and comparable to sumatriptan 100 mg
      for achieving a sustained pain-free state.

PMID- 12005272
TI  - Within-patient early versus delayed treatment of migraine attacks with
      almotriptan: the sooner the better.
AB  - BACKGROUND: Migraine sufferers typically have been instructed to delay triptan
      therapy until headache intensity is at least moderate. Recent data suggest that
      earlier use of triptans may be more beneficial. OBJECTIVE: To address the
      potential "within-patient" benefit of intervention with almotriptan 12.5 mg for
      migraine headache of mild intensity. METHODS: We performed a post hoc analysis of
      a subgroup of patients from a large, open-label, long-term clinical trial wherein
      762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity.
      Specifically, we evaluated the efficacy and safety of treatment in those patients
      who had treated at least 3 "mild" attacks and 3 "moderate/severe" attacks,
      examining rates of pain-free status, use of rescue medication, early recurrence,
      and adverse events for the first 3 mild and the first 3 moderate/severe attacks
      treated. RESULTS: There were 118 migraineurs and 708 attacks available for
      analysis. At 1 hour following treatment, pain-free status was achieved in 47% of
      mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2
      hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The
      chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks
      was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the
      percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue
      medication was required in 8% of mild attacks and in 13% of moderate/severe
      attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and
      33% for moderate/severe attacks (P<.01). There was no difference in the incidence
      of adverse events for mild versus moderate/severe attacks (6% versus 7%).
      CONCLUSION: These results support early intervention with oral triptan therapy.
      When used for mild intensity head pain, almotriptan 12.5 mg produced a
      significantly higher incidence of pain-free status at 1 and 2 hours and lower
      incidences of early headache recurrence or need for rescue medication.

PMID- 12005273
TI  - A long-term open-label study of oral almotriptan 12.5 mg for the treatment of
      acute migraine.
AB  - OBJECTIVE: Evaluate the long-term tolerability of almotriptan 12.5 mg for the
      treatment of acute migraine attacks occurring over a 6-month period. BACKGROUND:
      Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular
      selectivity for meningeal arteries and has demonstrated efficacy for the
      treatment of acute migraine in short-term controlled trials. METHODS: This was a
      6-month open-label study. Adults (18 years of age or older) were required to have
      a diagnosis of acute migraine with or without aura (according to the diagnostic
      criteria of the International Headache Society), a history of at least 1 year of
      moderate-to-severe migraine pain with at least two and a maximum of six migraines
      per month, and at least 24 hours of freedom from head pain between attacks.
      Patients were instructed to take a single 12.5-mg dose of almotriptan at the
      onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape
      medication could be taken; if relapse occurred in less than 24 hours, a second
      12.5-mg dose could be taken. Tolerability was assessed from the nature and
      incidence of all adverse events, and efficacy was assessed according to the end
      point of pain relief 2 hours following almotriptan administration. RESULTS: Of
      585 patients treated, 582 were included in the intent-to-treat population. The
      most frequent drug-related adverse events were nausea (3.1%) and dizziness
      (2.4%). No serious drug-related adverse events were reported, and no deaths
      occurred. Adverse events led to discontinuation of treatment in 36 patients
      (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six
      percent of patients achieved pain relief at 2 hours for all attacks treated, and
      49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain
      relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and
      pain-free rates were higher among those with moderate baseline pain. CONCLUSIONS:
      When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and
      effective for the long-term treatment of acute migraine.

PMID- 12005274
TI  - Frovatriptan for the acute treatment of migraine: a dose-finding study.
AB  - OBJECTIVE: To determine the optimal dose and tolerability of frovatriptan in the
      acute treatment of migraine. BACKGROUND: Frovatriptan has a distinctive
      pharmacological and pharmacokinetic profile compared with sumatriptan. A previous
      study has shown that frovatriptan doses of 2.5, 5, 10, 20, and 40 mg are equally
      effective in relieving headache with no evidence of a dose-response relationship.
      The incidence of adverse events tended to increase with doses of 10 mg and above.
      METHODS: This study was a randomized, double-blind, placebo-controlled, parallel
      group multicenter trial. Patients (n=635) took a single oral dose of placebo or
      frovatriptan, 0.5, 1, 2.5, or 5 mg, at the onset of a moderate or severe migraine
      headache and recorded headache intensity, functional impairment, and migraine
      associated symptoms over 24 hours. RESULTS: Frovatriptan 2.5 mg produced
      clinically and statistically significant headache relief 2 hours post-dose,
      whereas the effect of lower doses was not significantly different from that of
      placebo at that time point. The 2.5-mg dose also produced significant symptom
      relief and improvement in functional impairment. All doses of frovatriptan were
      well tolerated, and the majority of adverse events were of mild or moderate
      severity. CONCLUSION: It is concluded that the 2.5-mg dose of frovatriptan offers
      optimal efficacy and tolerability in the treatment of acute migraine. Higher
      doses do not appear to confer greater efficacy and are associated with an
      increased incidence of adverse effects.

PMID- 12005275
TI  - Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To investigate the tolerability and efficacy of rizatriptan 5 mg in
      adolescent migraineurs. METHODS: Randomized, double-blind, placebo-controlled
      study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or
      placebo (n = 147) for a moderate or severe headache and for up to two
      recurrences. Headache severity, presence or absence of associated symptoms, and
      functional disability were assessed over a 4-hour postdose period, and any
      adverse events were recorded. The primary efficacy measure was pain-free status
      at 2 hours postdose. RESULTS: Rizatriptan 5 mg was well tolerated. The most
      commonly reported adverse events (all with incidence of 5% or less) among
      patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue,
      nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32%
      for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients
      with pain relief (reduction of predose pain intensity to mild or none) at 2 hours
      was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates
      were higher than those typically observed in previous studies of rizatriptan in
      adults. Compared with placebo, rizatriptan significantly improved functional
      disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis
      showed a significant benefit of rizatriptan versus placebo in the percentage of
      patients who had pain relief when their migraine attacks were treated on weekends
      (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the
      weekend placebo response rate was similar to that seen in adults. CONCLUSIONS:
      Rizatriptan 5 mg was well tolerated and effective on some measures when used in
      adolescents for the treatment of a migraine attack.

PMID- 12005276
TI  - Naratriptan in the prophylaxis of cluster headache.
AB  - A 36-year-old man with cluster headache refractory to trials of standard
      prophylactic treatment and only partially responsive to parenteral sumatriptan
      and inhaled oxygen was admitted to an inpatient pain unit. The diagnosis of
      cluster headache was confirmed by direct observation of a typical attack. Despite
      efforts at prophylaxis, the patient continued to experience three to four severe
      headaches per day. Attempts to control his headaches with scheduled parenteral
      dihydroergotamine were successful, but headaches recurred when the medication was
      tapered, and continuous or intermittent use of parenteral dihydroergotamine was
      not felt to be a practical option for the patient. Naratriptan 2.5 mg twice daily
      completely abolished his headaches, which recurred when the medication was
      discontinued. No electrocardiographic or laboratory abnormalities were observed
      during treatment, and the patient reported no side effects.

PMID- 12005277
TI  - New paradigms in the recognition and acute treatment of migraine.
AB  - It would be ideal if clinical decisions regarding acute migraine treatment could
      be made on the basis of three parameters: a critical appraisal of available
      scientific evidence, clinical experience (including knowledge of the individual
      patient and his/her attack characteristics), and, of course, patient preferences.
      Patients are likely to prefer agents that offer rapid relief, pain-free status
      within 2 hours, no recurrence or need for rescue medication, extended time to
      recurrence (if present), consistency of therapeutic effect over multiple attacks,
      oral administration. good tolerability, safety, and minimal drug interactions.
      Fortunately, a number of specific therapies now are available which place these
      objectives within the patient's reach. Ongoing barriers to optimal migraine care
      include underrecognition, underconsultation, undertreatment, restrictions imposed
      by insurance companies, and exaggerated concerns regarding the safety of the
      triptans. Overcoming these barriers is likely to prove a more important
      contribution to patient care than endeavoring to establish the relative merits of
      one triptan over another. We have described in detail a number of strategies for
      improving recognition and treatment of migraine. Many headache specialists now
      believe that recurrent episodes of disabling headache, with a stable pattern over
      years, should be viewed as migraine until proven otherwise. In the end, this may
      represent the most useful paradigm in the primary care setting, where time is of
      the essence. Studies to validate this approach are needed. Acute treatment
      intervention that is based on scientific evidence, clinical experience, and
      patients' needs and desires will provide better outcomes than those presently
      obtained. Preliminary evidence favors early intervention with oral triptans, and
      randomized, prospective, double-blind, placebo-controlled studies, ideally
      employing a crossover design, are required to confirm this. The US Consortium's
      evidence-based guidelines, the National Headache Foundation's standards of care,
      and the Canadian guidelines have applied the standards of scientific inquiry to
      the field of headache management and "translation" of these guidelines into
      practical instruments for clinicians through vehicles such as the Primary Care
      Network's Patient-Centered Strategies for Effective Management of Migraine should
      raise the general standard of care for patients with migraine. Last, but far from
      least, initiatives undertaken by the World Health Organization (WHO) will add
      credibility to the many layfolk and professionals who have struggled to present
      headache as a disabling disorder worthy of scientific investigation and
      aggressive medical management. The WHO states: "These common complaints impose a
      significant health burden ... Despite this, both the public and the majority of
      healthcare professionals tend to perceive headache as a minor or trivial
      complaint. As a result, the physical, emotional, social and economic burdens of
      headache are poorly acknowledged in comparison with those of other, less
      prevalent, neurologic disorders." Migraine is finally out of the closet.

PMID- 12005278
TI  - Headache recurrence as a criterion for assessing efficacy of triptans: a
      perspective.

PMID- 12005279
TI  - Evidence-based assessment of pregnancy outcome after sumatriptan exposure.
AB  - OBJECTIVE: Assessment of best available evidence for tolerability of sumatriptan
      after inadvertent exposure during pregnancy. BACKGROUND: Migraine's demography
      suggests that inadvertent exposure to acute therapies is likely during the
      earliest undiagnosed stages of pregnancy. The tolerability of such therapies
      under these conditions is not amenable to clinical trial for ethical reasons. In
      the United States, sumatriptan is currently labeled pregnancy category C (ie, not
      recommended for use during pregnancy unless the potential benefit justifies the
      potential risk to the fetus). METHODS: Three types of adverse events were
      studied: spontaneous abortion, fetal abnormality, and obstetric complications.
      Traditional evidence-based criteria were used to assess a search-protocol product
      of four clinical studies and two case reports. RESULTS: The single positive
      finding ("preterm delivery" without low birth weight) was in the smallest study;
      this study was retrospective and the finding was externally inconsistent with the
      other three larger studies, all of which were prospective. No study followed
      children for more than 4 years, which is the period needed to identify the
      maximum number of congenital anomalies. Rigorous teratological technique was
      generally not employed. Post hoc power calculations were used to provide
      parameters of the hazard detectable by these studies in aggregate. CONCLUSIONS:
      Pregnancy categories B and C both seem feasible for sumatriptan. Within the
      limits of the examined studies, there is no evidence for any specific effect of
      sumatriptan on pregnancy outcome. Patients inadvertently exposed to sumatriptan
      during an early stage of pregnancy should be reassured by these data.

PMID- 12005280
TI  - The patient's perspective.

PMID- 12005281
TI  - Aneurysmal "thunderclap" headache without subarachnoid hemorrhage.

PMID- 12005282
TI  - Triptans for migraine prodrome.

PMID- 12005283
TI  - Control of topiramate-induced paresthesias with supplemental potassium.

PMID- 12005284
TI  - Topiramate-induced myopia.

PMID- 12005285
TI  - Oral magnesium load test in patients with migraine.
AB  - OBJECTIVE: To determine whether migraineurs may have a systemic deficiency of
      magnesium. BACKGROUND: Magnesium deficiency has been shown to play a potential
      role in the pathogenesis of migraine, but there are no data on total body
      magnesium status in migraineurs. METHODS: An oral magnesium load test was
      performed by giving 3000 mg of magnesium lactate during a 24-hour interictal
      period to 20 patients with migraine (15 women and 5 men; mean age, 37.9 years)
      and 20 healthy volunteers (16 women and 4 men; mean age, 39.6 years). Baseline
      and postload magnesium concentrations were determined from serum and 24-hour
      urine specimens. RESULTS: There was no significant difference between the groups
      in the baseline serum and urine magnesium concentrations, although the latter
      tended to be lower (P = .064) in the migraine group. The postload magnesium
      concentrations were significantly higher within both the migraine (P < .0001 and
      P < .0001) and the control (P = .0009 and P < .0001) groups compared to the
      baseline values. After loading, the 24-hour urinary magnesium excretions were
      significantly lower (P = .0007) in the patients with migraine than in the
      controls, but serum values did not differ. CONCLUSIONS: Magnesium retention
      occurs in patients with migraine after oral loading, suggesting a systemic
      magnesium deficiency.

PMID- 12005286
TI  - Endothelin-1 plasma levels in cluster headache.
AB  - BACKGROUND AND OBJECTIVE: A role for endothelin-1, a potent vasoconstrictor
      peptide, in some cerebrovascular diseases has been proposed. To obtain
      preliminary data about peripheral concentrations of endothelin-1 in acute cluster
      headache, we measured the plasma endothelin-1 secretory pattern in 10 men with
      cluster during and independent of a headache attack. METHODS: We collected blood
      samples for plasma endothelin-1 determinations at 0, 15, 30, 45, 60, 90, and 120
      minutes during a cluster attack and closely monitored blood pressures. We
      repeated the same sampling during an asymptomatic period. RESULTS: The mean
      values of plasma endothelin-1 (before a cluster headache, 3.3 +/- 0.3 pg/mL)
      significantly increased (F = 2.578, P < .05) during an attack, reaching their
      peak at 30 minutes (5.0 +/- 0.5 pg/mL, P < .05). We found no significant
      variations in mean arterial pressure. CONCLUSION: Endothelin-1 may play a role in
      the pathophysiology of cluster attacks. The increase in plasma observed during
      cluster attacks may be linked to alterations in systemic hemodynamics and
      vascular tone.

PMID- 12005287
TI  - Impaired circadian rhythmicity of nociceptive reflex threshold in cluster
      headache.
AB  - BACKGROUND: Alteration of circadian rhythmicity involving several endocrinologic
      and autonomic parameters has been observed in cluster headache. OBJECTIVES: To
      explore whether circadian failure of the pain control system may exist in cluster
      headache. METHODS: The nociceptive flexion reflex threshold was studied in 25
      patients with episodic cluster headache (14 active, 11 in remission) and 6
      patients with chronic cluster headache, along with 10 normal volunteers
      throughout a 24-hour period. The reflex response was evoked at the level of the
      biceps femoris by stimulating the sural nerve at the ankle. Single and population
      mean cosinor methods were used to detect the circadian rhythmicity. RESULTS: In
      the patients with episodic cluster headache, a significant reduction in the
      nociceptive flexion reflex threshold was observed in both the active subgroup and
      the subgroup in remission (P < .05). In these patients, persistence of a
      significant 24-hour rhythm during both the active period and remission was
      observed, but a shift of the phase was observed during clinical activity when
      compared with the remission period. A lack of circadian nociceptive flexion
      reflex threshold rhythmicity was found in the patients with chronic cluster
      headache. CONCLUSIONS: Our findings suggest that in cluster headache there may be
      impairment of the pain control system that is associated with periodic failure of
      the mechanisms involved in the organization of biological rhythms.

PMID- 12005288
TI  - Ophthalmoplegic migraine with reversible thalamic ischemia shown by brain SPECT.
AB  - Two patients who presented with ophthalmoplegic migraine underwent
      electroencephalography, brain magnetic resonance imaging, cerebral angiography,
      and technetium Tc 99m ethyl cysteinate dimer single photon emission computed
      tomography (SPECT) during an attack. Follow-up SPECT was performed after
      neurologic symptoms resolved. In both patients, SPECT during an attack of
      ophthalmoplegia and headache demonstrated significantly decreased regional
      cerebral blood flow (rCBF) in the thalamus on the side of the ophthalmoplegia;
      rCBF reverted to normal on a follow-up SPECT during the symptom-free period.
      These findings suggest reversible ischemia in the territories of perforating
      branches of the posterior cerebral artery may accompany ophthalmoplegic migraine
      and possibly bear some relationship to the clinical features.

PMID- 12005289
TI  - Hemiplegic cluster.
AB  - We report four cases of a new variant of cluster headache associated with
      hemiparesis. Clinical similarities with hemiplegic migraine suggest that
      hemiplegic cluster, too, may be a channelopathy. One of our patients had a family
      history suggestive of an autosomal dominant inheritance.

PMID- 12005290
TI  - Ophthalmoplegic migraine with reversible enhancement of intraparenchymal abducens
      nerve on MRI.
AB  - We describe a patient with ophthalmoplegic migraine and right abducens nerve
      palsy, in whom serial magnetic resonance imaging showed a transient, gadolinium
      enhancing lesion in the right lower pons, during both headache and the headache
      free period. The enhancing linear lesion was felt to represent intraparenchymal
      fibers of the affected abducens nerve. The possible pathophysiology of this
      unique finding is discussed.

PMID- 12005291
TI  - Occipital condyle syndrome.
AB  - OBJECTIVE: Review the clinical features of occipital condyle syndrome.
      BACKGROUND: Occipital condyle syndrome consists of unilateral occipital region
      pain associated with ipsilateral 12th cranial nerve paresis. It is typically due
      to metastasis to the skull base and is underdiagnosed. DESIGN: We report a
      retrospective case series of 11 patients (8 men, 3 women), aged 32 to 72 years.
      RESULTS: Eleven cases of occipital condyle syndrome were identified. All patients
      complained of severe occipital region pain. In addition, 2 patients complained of
      ipsilateral ear or mastoid pain, 2 noted associated vertex pain, and 2 had
      frontal region pain. Six of the 11 cases involved the right side. In all
      patients, the occipital pain was ipsilateral to the 12th nerve paresis. All
      patients were mildly dysarthric, and 3 had dysphagia. In 7 of the 11 patients,
      occipital region pain preceded the hypoglossal paresis by several days to 10
      weeks. On examination, tenderness to palpation of the occipital region was noted
      in all patients. All 11 patients had unilateral hypoglossal paresis. Skull films
      were abnormal in 2 of 5 patients for whom they were obtained, and tomograms were
      abnormal in 1 of 2 patients. High-quality computed tomography, bone scanning, and
      magnetic resonance imaging were abnormal in all cases in which they were
      performed. Nine patients had a known primary malignancy. The most common
      malignancies were breast cancer in women (2 of 3) and prostate cancer in men (4
      of 8). In 2 patients, occipital condyle syndrome was the initial manifestation of
      a metastatic lesion. Radiation therapy was the treatment of choice for the
      occipital region pain. CONCLUSION: Occipital condyle syndrome is a rare, but
      stereotypic syndrome. Early detection has important therapeutic implications.
      Evaluation of the craniovertebral junction with special attention to the
      occipital condyles should be a routine part of all brain and cervical spine
      radiologic examinations, and the possibility of occipital condyle syndrome,
      particularly when patients have persistent occipital pain and a history of
      cancer, should be considered.

PMID- 12005292
TI  - Red ear syndrome and migraine: report of eight cases.
AB  - We describe eight idiopathic cases of red ear syndrome in seven children and one
      adult. All were migraineurs with a history of paroxysmally painful and red ear,
      unilateral or alternating, in isolation or associated with migraine attacks. The
      reported duration of these episodes varied from 30 minutes to 1 hour. Neurologic
      examination, brain MRI and CT scans, and x-rays of the cervical spine were
      normal. The close temporal relationship between the "red ear episodes" and
      migraine attacks suggests an association between the two conditions.

PMID- 12005293
TI  - Migraine prevention and errors in living: Dr. Graham's lessons for patients and
      physicians.
AB  - John R. Graham, MD (1909-1990), the "father of headache management," left us and
      our patients with migraine with valuable advice ... advice based on extensive
      experience in headache management which, at the time of his retirement, spanned
      more than half a century.

PMID- 12005294
TI  - Cognitive and social correlates of highly prevalent endemic diseases: the Rodney
      Dangerfield effect.

PMID- 12005295
TI  - The patient's perspective: a friend like no other.

PMID- 12005296
TI  - The migraine with aura that wasn't.

PMID- 12005297
TI  - Spontaneous intracranial hypotension resulting in coma.

PMID- 12005298
TI  - Re: Cluster headache is not associated with signs of a systemic inflammation.

PMID- 12005299
TI  - Characteristics of chronic posttraumatic headache.

PMID- 12005300
TI  - The poster exhibition at the 2001 IHC meeting: a time for new ideas, obsessions,
      and agendas.

PMID- 12005301
TI  - Comparison of triptan tablet consumption per attack: a prospective study of
      migraineurs in Spain.
AB  - OBJECTIVES: To compare patient self-reported tablet consumption of rizatriptan 10
      mg per attack (24 hours) with that of sumatriptan 50 mg, zolmitriptan 2.5 mg, and
      naratriptan 2.5 mg on an unselected, prescription-based, Spanish migraine
      population. METHODS: One hundred twenty community pharmacies recruited patients
      with migraine, who used their pharmacies, to fill a triptan prescription. In
      diaries, patients recorded baseline pain intensity and the number of triptan
      tablets and additional medication taken per attack. Patients treated a maximum of
      three attacks. Analysis of variance or the Student t test and chi-square or
      Fisher exact tests were used for univariate comparisons. Hochberg corrections
      were used for multiple-group comparisons. A generalized estimating equation
      method was used to correct for within-subject correlation. Adjusted odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Two hundred
      thirty-one patients (84% women) treated 589 evaluable migraine attacks
      (sumatriptan, n = 135; naratriptan, n = 90; zolmitriptan, n = 149; rizatriptan, n
      = 149). Triptan tablet consumption per attack (mean +/- SD) for rizatriptan (1.24
      +/- 0.56) was significantly lower than that of sumatriptan (1.75 +/- 1.2; P<
      .05), zolmitriptan (1.61 +/- 0.86; P < .05), or naratriptan (1.46 +/- 0.62; P=
      .05). The average number of triptan tablets taken and additional medication use
      increased according to baseline pain severity. More attacks were treated with one
      tablet of rizatriptan (81.2%) than with one tablet of sumatriptan (51.9%),
      zolmitriptan (55.7%), or naratriptan (60%). The probability of using more than
      one triptan tablet per attack (24 hours) was more than three times greater for
      sumatriptan (adjusted OR = 3.71; CI, 2.05 to 6.7; P = .001) and zolmitriptan
      (adjusted OR = 3.32; CI, 1.82 to 6.17; P = .001), and more than two times greater
      for naratriptan (adjusted OR = 2.66; CI, 1.36 to 5.21; P =.004) than for
      rizatriptan. CONCLUSIONS: Rizatriptan was associated with significantly lower
      triptan tablet use and additional medication use per attack than the other
      triptans. Additional randomized studies are needed to confirm the conclusions of
      this study.

PMID- 12005302
TI  - How does almotriptan compare with other triptans? A review of data from placebo
      controlled clinical trials.
AB  - Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral
      bioavailability than any other triptan, with more than two thirds of the
      administered dose absorbed within the first hour both inside and outside of a
      migraine attack. Gender or the presence of food in the stomach does not affect
      its pharmacokinetic profile, and the compound has no clinically relevant
      interactions with other drugs. Among the available triptans, response rates at 2
      hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan
      12.5 mg provides similar efficacy, with significant advantage over placebo at 30
      minutes and a reliable consistency (75% in two of three attacks). Headache
      typically recurs in 25% to 45% of patients with most triptans. The recurrence
      rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The
      tolerability of almotriptan 12.5 mg is close to that of placebo with a low
      incidence of central nervous system side effects and chest symptoms. In
      conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in
      combination with excellent tolerability, make it an attractive choice in the
      acute treatment of migraine attacks.

PMID- 12005303
TI  - Clinical significance of transvaginal color Doppler ultrasonography of the
      ovarian artery as a predictor of ovarian response in controlled ovarian
      hyperstimulation for in vitro fertilization and embryo transfer.
AB  - PURPOSE: Our purpose was to verify whether the blood flow impedance of the
      ovarian stromal artery in transvaginal color Doppler ultrasonography can predict
      the in vitro fertilization and embryo transfer (IVF-ET) outcomes. METHODS:
      Transvaginal color Doppler ultrasonographic examinations were performed in 99
      patients undergoing controlled ovarian hyperstimulation (COH) for IVF-ET. The
      pulsatility index (PI) was evaluated in the bilateral ovarian stromal arteries on
      the starting day of COH (PI1) and the day of hCG administration (PI2). The
      patients were classified into three groups by the mean PI1, PI2, and API (PI1 -
      PI2), respectively, and the IVF-ET outcomes were analyzed and compared. RESULTS:
      There were no significant differences in the duration of COH, the total dosage of
      gonadotropins used for COH, the serum E2 concentration on day of hCG
      administration, the number of follicles on the day of hCG administration, the
      number of oocytes retrieved or fertilized in vitro, and the number of embryos
      transferred between their respective PI1, PI2, and API values. However, the
      pregnancy rate was significantly lower in the higher PI1 and PI2 groups than in
      the lower groups (p < 0.05, p < 0.05). Significant positive correlations were
      also found between PI1 and PI2 and the total dosage of gonadotropins for COH (Y=
      0.483X + 27.1, r = 0.052, p < 0.05; Y = 0.877X + 26.6, r = 0.075, p < 0.05).
      CONCLUSIONS: Our results showed that the lower PI in the ovarian stromal artery
      during COH is associated with the higher the pregnancy rate and the smaller
      amount of gonadotropins used for effective COH. This study suggests that the
      color Doppler ultrasonographic index (PI) of the ovarian stromal artery during
      COH may be useful for predicting the success of IVF-ET in infertile patients.

PMID- 12005304
TI  - Donor oocyte cytoplasmic transfer did not enhance implantation of embryos of
      women with poor ovarian reserve.
AB  - PURPOSE: To determine whether donor oocyte cytoplasm transferred into the oocytes
      of women < or = 40 years or with diminished ovarian reserve would enhance embryo
      quality, implantation, or pregnancy rates. METHODS: Study subjects included women
      > or = 40 years (15) or with abnormal FSH levels (3). Healthy volunteers (18)
      produced oocytes for cryopreservation. Donor oocytes were thawed and cytoplasm
      from surviving oocytes was injected with a single sperm into the cytoplasm of
      recipient oocytes. Outcome measures included embryo quality scores, implantation,
      and pregnancy rates. RESULTS: Eighteen donors produced 213 oocytes for
      cryopreservation and 39/171 (22.8%) survived thawing. Eighteen recipients
      initiated 25 IVF cycles with embryo transfer in 20 cycles after cytoplasmic
      transfer (CT). Four cycles resulted in three biochemical losses and one aneuploid
      clinical loss. Embryo quality did not improve with CT compared to pre-CT IVF
      cycles in six recipients. CONCLUSIONS: CT with cryopreserved donor oocyte
      cytoplasm did not enhance success in women with advanced reproductive age or low
      ovarian reserve.

PMID- 12005305
TI  - Improving eggs: more questions than answers.

PMID- 12005306
TI  - Expression of insulin-like growth factor (IGF), IGF receptor, and IGF-binding
      protein messenger ribonucleic acids in luteinized granulosa cells from different
      size follicles after controlled ovarian hyperstimulation.
AB  - PURPOSE: This study was conducted to determine the gene expression of insulin
      like growth factors (IGFs), their receptors, and binding proteins (IGFBPs) in
      human luteinized granulosa cells collected during ovum retrieval. METHODS: cDNA
      probes were used to analyze the gene expression of IGF-I, IGF-II, IGF type 1
      receptor (IGFR-1), IGF type 2 receptor (IGFR-2), and IGFBP-1 to -6 in luteinized
      granulosa cells. RESULTS: The levels of IGFBP-5 transcripts of the luteinized
      granulosa cells increased with increasing follicular fluid (FF) volume when
      follicles were grouped into 3 volume catagories of < or = 1.5 mL: > 1.5 mL but <
      or = 4.5 mL; and > 4.5 mL (0.28 +/- 0.64 vs. 0.41 +/- 0.76 vs. 0.46 +/- 0.92, p =
      0.037). CONCLUSIONS: The increased levels of IGFBP-5 transcripts in luteinized
      granulosa cells found with increased follicular fluid volume after COH may favor
      a shift toward diminished action of IGFs in larger follicles immediately prior to
      ovulation.

PMID- 12005307
TI  - Results of intracytoplasmic sperm injection of single oocyte in 362 unstimulated
      cycles.
AB  - PURPOSE: The purpose was to test the adequacy of unstimulated cycles for
      intracytoplasmic sperm injection (ICSI) and to evaluate implantation and
      pregnancy rates in three different age groups. METHODS: ICSI was performed in 362
      unstimulated cycles in women up to 45 years old. All cycles were monitored by
      serum estradiol, urinary LH, and ultrasound. RESULTS: The delivery rate per
      started cycle was higher in patients younger than 36 (9.4%) than in cycles with
      patient's age between 36 and 39 years (4.8%) or older than 40 (4.6%) but the
      difference was not statistically significant. In all groups, the fertilization
      rate was similar (70.4, 77.6, and 84.8%, respectively). The pregnancy rate per
      cycle and the pregnancy rate per puncture was similar in the group of patients in
      age between 36 and 39 years (8.3 and 9.7%) and those older than 40 (7.7 and
      9.3%). CONCLUSIONS: Unstimulated cycles monitored by serum estradiol, urinary LH,
      and ultrasound can produce an acceptable pregnancy rate after ICSI procedure only
      in patients younger than 36.

PMID- 12005308
TI  - Human papillomavirus and blastocyst apoptosis.
AB  - PURPOSE: The effect of human papillomavirus (HPV) DNA from the E6-E7 region on
      the integrity of DNA in blastocyst stage embryonic cells was studied. The study
      design paralleled the event whereby HPV DNA from the infecting virus would target
      host cell DNA. The objectives were (a) to determine if the DNA of blastocysts
      were disrupted by the presence of HPV DNA and (b) to determine if the intensity
      of DNA damage was associated with the type of HPV. METHODS: This study involved
      superovulating female mice, mating, collecting one-cell embryos, and culturing to
      the expanded blastocyst stage. The blastocysts were infected with PCR-synthesized
      DNA fragments from either HPV type 16, 18, 31, or 33. The blastocyst DNA were
      analyzed by comet assay after 24 h of incubation. The fluorescent images were
      digitized and the pixel intensity of each blastocyst was measured. RESULTS: Only
      the DNA of HPV type 16 was associated with significant DNA fragmentation in
      comparison with the other HPV types. There was no relationship between HPV DNA
      fragment size and the intensity of DNA fragmentation. CONCLUSIONS: The data
      suggested that one mode of action of HPV type 16 was to initiate apoptosis of
      embryonic cells through DNA fragmentation. The effect of HPV 16 occurred rapidly
      within 24 h. The intensity of DNA damage was not linked to the specific type of
      HPV. However, the results do not rule out the other HPV types affecting embryos
      under conditions different from this study.

PMID- 12005309
TI  - Protein supplementation of human IVF culture media.
AB  - This review travels the road of protein supplementation in embryo culture
      development-from whole crude plasma in the mid Twentieth century moving through
      to the completely genetically engineered human albumin with successful births at
      the beginning of the Twenty-first.

PMID- 12005310
TI  - A case of twin pregnancy with complete hydatidiform mole and coexisting fetus
      following IVF-ET.
AB  - Twin pregnancy consisting of complete hydatidiform mole (H-mole) and a coexisting
      fetus occurs with an estimated incidence of 1 per 22,000-100,000 pregnancies. The
      incidence of this unusual twin pregnancy with complete H-mole and a coexisting
      fetus after in vitro fertilization and embryo transfer (IVF-ET) is not thought to
      be greater than that of general population. We present an unusual twin pregnancy
      with complete H-mole and a coexisting fetus that occurred following IVF-ET, which
      was terminated at 21 weeks of gestation and developed into nonmetastatic
      gestational trophoblastic tumor.

PMID- 12005311
TI  - Birth of a healthy male after frozen thawed blastocyst transfer following
      intracytoplasmic injection of frozen thawed testicular spermatozoa from a man
      with nonmosaic Klinefelter's syndrome.
AB  - We here report on a birth of a male, with normal karyotype, after frozen thawed
      blastocyst transfer following intracytoplasmic injection of frozen thawed
      testicular spermatozoa from an azoospermic 27-year-old man with nonmosaic
      Klinerfelter's syndrome. Testicular sperm were retrieved by percutaneous needle
      biopsy.

PMID- 12005312
TI  - Pronuclear abnormalities and cytoskeletal organization during assisted
      fertilization in a patient with multifollicular ovarian response.
AB  - PURPOSE: To analyze the distribution of a tubulins and acetylated alpha tubulins
      and the chromatin configuration in abnormally fertilized zygotes from a patient
      with a multifollicular ovarian response after in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). METHODS: Immunofluorescence and phase
      contrast microscopy was performed in abnormally fertilized zygotes. RESULTS:
      After phase contrast microscopy analysis, immunofluorescence staining was
      performed in 20 oocytes that developed > or = 3 pronuclei (PN) and karyomeres
      after IVF-ICSI. Around 80% of the abnormal zygotes from IVF were the consequence
      of monospermic fertilizations. Retention of the second polar body (PB) and the
      presumptive split of > or =1 PN within the cytoplasm were the main events present
      in most oocytes after IVF-ICSI. CONCLUSIONS: Fluorescence labeling of selected
      sperm and oocyte components affords a unique view of abnormal fertilized zygotes.
      Surprisingly, anomalies detected after IVF-ICSI showed similar etiologies in this
      special group of zygotes.

PMID- 12005313
TI  - A uterine ultrasonographic scoring system as a method for the prognosis of embryo
      implantation.
AB  - PURPOSE: The objective of the present study was to evaluate an ultrasonographic
      uterine scoring system as a method for the prognosis of embryo implantation in
      patients submitted to ICSI. METHODS: A total of 562 patients submitted to an ICSI
      program were prospectively evaluated on the day of hCG administration in terms of
      the following ultrasonographic uterine parameters: A. Endometrial thickness (<
      7.0 mm = 0; 7 a 14 mm = 3; > 14 mm = ); B. Endometrial layering (three lines = 2;
      absence of three lines = 0); C. Myometrial contractions in 2 min (< 3 = 0; > or =
      3 = 3); D. Uterine artery Doppler flow (> 3 = 0; 2.2 a 3 = 22; > or = 2 .19 = 3);
      E. Endometrial power Doppler (The endometrium was divided into four equal
      quadrants and classified as grade I = 1; II = 2; III = 3; IV = 4, according to
      the visualization of the power Doppler in the quadrants). The colour Doppler
      signal was considered to be positive when it reached at least the basal layer of
      the endometrium; F. Myometrial power Doppler (absent = 0 weakly present 2;
      strongly present = 3); G. Myometrial echogenicity (homogeneous = 2; inhomogeneous
      = 0). The patients were divided into 4 groups according to total score: Group I,
      score < 10: Group II, score 10-14, Group III, score 15-17 and Group IV, score 18
      20. RESULTS: The uterine parameters using an ultrasonographic scoring system are
      inversely correlated with patient age (p < 0.0001). The number of days of
      stimulation with FSH did not differ (p = 0.10) between groups. The number of
      follicles measuring >16 mm was different (p = 0.01) between groups. The number of
      metaphase II oocytes also did not differ significantly between groups (p = 0.45).
      The fertilization rate was also similar (p = 0.10) for all groups. The number of
      transferred embryos was different between groups (p = 0.02). The rate of embryo
      implantation did not differ (p = 0.60) between groups. Finally, the pregnancy
      rates did not differ significantly (p = 0.93) between groups. CONCLUSIONS: The
      ultrasonographic evaluation of uterine parameters on the day of hCG
      administration using a scoring system is inversely correlated with patient age.
      In the present study, the use of this ultrasonographic score method could not
      identify a population with greater uterine receptivity.

PMID- 12005314
TI  - Clinical assessment still matters.

PMID- 12005315
TI  - Relation between spasticity and strength in individuals with spastic diplegic
      cerebral palsy.
AB  - The relation between spasticity and strength in individuals with cerebral palsy
      (CP) has not been extensively researched. Knee and ankle spasticity and strength
      were quantified in a retrospective analysis of 60 individuals with spastic
      diplegic CP (mean age 12 years, range 3 to 38) and a group of 50 individuals
      without disabilities (WD group; mean age 12 years, range 4 to 36). Spasticity was
      measured using a KinCom dynamometer that stretched the passive knee flexors or
      ankle plantarflexors at different speeds and recorded the amount of resistive
      torques. For the strength tests, the participant performed a maximum contraction
      of the knee flexors/extensors and ankle plantarflexors/dorsiflexors throughout
      their range of motion at a speed of 10 degrees/s on the dynamometer. Pearson's
      correlation coefficient was used to determine if a relation existed between
      spasticity and strength within the same muscle group and in opposing muscle
      groups at the knee and ankle joints. A t-test was performed to determine if
      greater spasticity and less strength existed at the ankles compared with the
      knees in those with CP. Results show that there was no relation between
      spasticity and strength either within the same muscle group or at opposing muscle
      groups at the knee and ankle joints in persons with CP. Individuals with spastic
      diplegic CP were more involved (greater spasticity, less strength) distally at
      the ankles compared with the knees. The findings conflict with the literature,
      which contains several assumptions, one of which is that a spastic muscle is a
      strong muscle and that spasticity causes weakness in the opposing muscle group.
      We found no relation between spasticity and strength in individuals with CP. Our
      findings support the literature, which states that individuals with spastic
      diplegic CP are more involved distally compared with proximally in the lower
      extremities.

PMID- 12005316
TI  - Architecture of the medial gastrocnemius in children with spastic diplegia.
AB  - Ultrasound images were obtained of the medial gastrocnemius at different ankle
      joint positions with the knee extended. Fascicle length and deep fascicle angle
      were measured in five normally developing adults (mean age 33 years, age range 24
      to 36 years) and in five normally developing children (mean age 7.8 years, age
      range 7 to 11 years), and in seven children with spastic diplegia (mean age 10
      years, age range 6 to 13 years). These architectural variables were similar in
      the groups of normally developing adults and children. Importantly, no
      statistical difference could be found between the normally developing children
      and those with diplegia for fascicle length. Deep fascicle angles were reduced
      significantly in the clinical group at a particular ankle joint angle but not at
      the resting angles. The difference in deep fascicle angles is explained as a
      function of resting muscle length and is not attributed any clinical importance.
      Our results do not explain the structural origin of muscle contracture
      explicitly. However, they do indicate that most of the fixed shortness in the
      medial gastrocnemii of ambulant children with spastic diplegia is not due to
      reduced muscle fibre length. We suggest that muscle contracture may be better
      explained in terms of shortness of the aponeuroses of pennate muscles, such as
      the medial gastrocnemius, through reduced muscle fibre diameter.

PMID- 12005317
TI  - Treatment of ADHD in neurofibromatosis type 1.
AB  - Forty-six of 93 children with neurofibromatosis type 1 (NF1) were found to
      satisfy the diagnostic criteria for attention-deficit-hyperactivity disorder
      (ADHD). Detailed comparisons were made among 20 children with NF1 and ADHD (12
      males, 8 females; mean age 10.7 years, SD 2.2), 26 control children with NF1 (15
      males, 11 females; mean age 11.3 years, SD 2.3), 14 control children with ADHD (7
      males; mean age 9.9 years, SD 1.9), and 14 normally developing control children
      (7 males; mean age 11.2 years, SD 2.8). Children with NF1 and ADHD had the lowest
      IQ scores among the four groups. Test of Variables of Attention (TOVA) scores
      were poorer in the NF1-ADHD and ADHD control groups than in the two non-ADHD
      groups. Those with NF1 and ADHD were rated significantly poorer on the Child
      Behavior Checklist (CBCL) than were the NF1 control group. By administrating low
      doses (5 to 15 mg) of methylphenidate to the NF1-ADHD group, significantly
      improved TOVA scores were obtained. One-year follow-up yielded significantly
      improved CBCL scores. Our results show a high incidence of ADHD in NF1 and
      support an association between ADHD and learning and social problems in children
      with NF1. It was demonstrated that stimulant medication can lead to improvement
      in cognitive, academic, and social problems of children with NF1 and ADHD.

PMID- 12005318
TI  - Visual function and EEG reactivity in infants with perinatal brain lesions at 1
      year.
AB  - The aim of this study was to examine the correlation between EEG, visual, and
      brain MRI findings in 19 term infants with perinatal brain lesions. All 19 had
      their visual acuity and visual fields assessed and had an EEG and a brain MRI
      performed at 1 year of age. Four of the five infants with normal optic radiations
      and occipital cortices on MRI had normal vision. Involvement of optic radiations
      and occipital cortices was only associated with visual abnormalities in eight of
      14 infants. The correlation between visual abnormalities and EEG findings was
      stronger. All infants with a completely normal EEG from the posterior regions had
      normal vision and all those with an EEG non-reactive to eye closure had visual
      abnormalities, irrespective of MRI data. A reactive EEG with other abnormal
      features (such as spikes, rapid or slow activities) was accompanied by abnormal
      vision in five of eight participants. Results suggest that there is a better
      correlation between visual function and EEG activity than between visual function
      and involvement of the classical visual areas of the occipital cortex and optic
      radiations on brain MRI at 1 year of age.

PMID- 12005319
TI  - Use of a lying hip abduction system in children with bilateral cerebral palsy: a
      pilot study.
AB  - Fourteen children aged 4 to 14 years with hip subluxation due to cerebral palsy
      (CP) were considered for a trial in a lying hip abduction system (Jenx Dreama,
      Jenx Limited, Sheffield, UK). Baseline data were recorded for 6 months, then
      assessments of the system were made for one year at 6 and 12 months. Assessments
      consisted of hip radiographs in the standard position, a parental questionnaire,
      and a sleep chart, which was completed by parents every Friday night during the
      trial. Three children could not enter the trial because of general sleep
      problems, and three could not complete it because they were unable to sleep with
      the system. One further child withdrew from the study just before the end because
      of unacceptable deterioration for which surgery was needed. The remaining seven
      children completed the trial and there was an overall improvement in rate of hip
      migration percentage on the right from 7% per annum in the baseline period to 4%
      with the system (p<0.05). On the left, changes were -3% and 0% respectively (ns).
      Average sleep at night changed from 9 to 9.4 hours (ns) and wakenings/night from
      1 to 1.3 (ns). On the parental questionnaire, there were significant improvements
      noted with the system in position for seating and sleeping, ease of hip abduction
      for washing, and with pain reduction. This pilot study supports the use of this
      type of lying system but further studies are needed to establish the
      acceptability and efficacy of these systems, particularly in children aged 2 to 5
      years when irreversible bony deformities of the hip tend to occur.

PMID- 12005320
TI  - Maturation of finger-synchronization skills.
AB  - The ability to move two fingers at the same time was measured in young and older
      adults. This study measured the accuracy with which 45 normally developing
      children (23 boys, 22 girls; mean ages 8.4 and 8.3 years respectively) and 49
      young adults (25 males, 24 females; mean ages 19.8 and 20.5 years respectively)
      could synchronize movements of two fingers when making or breaking contact with
      circular metal discs. A portable electronic instrument displayed the timings. To
      measure 'in-phase' skills, attempts were made to contact both discs
      simultaneously with the two index fingers or to break both contacts; asynchrony
      was only a few milliseconds and differences between children and adults were
      insignificant. To measure 'antiphase' skills, attempts were made with the index
      and middle fingers to make contact simultaneously with one disc while breaking
      contact with the other; asynchrony was larger. Usually one contact was made and
      later the other was broken; for a while both fingers touched (overlap). Rarely
      one contact was broken before the other was made; for a while neither finger
      touched (gap). Boys' periods of overlap were longer than those of men and women;
      on both sides these differences were highly significant statistically (p<0.0001).
      Boys' errors on the right side were also significantly greater than those of
      girls. On both sides, mean errors of girls were higher than those of men and
      women: three of the four sets of data reached statistical significance. While
      boys' performance improved with age, that of girls was static. Children achieved
      an essentially adult level of control for in-phase skills but with antiphase
      skills the children, and especially the boys, had clearly poorer performances.

PMID- 12005321
TI  - Correlation between physical functioning and gait measures in children with
      cerebral palsy.
AB  - The primary aim of this investigation was to assess the correlation between the
      POSNA Musculoskeletal Functional Health Questionnaire (POSNA) and gait analysis
      in children with cerebral palsy (CP). POSNA and computerized gait analysis were
      used to evaluate individuals with CP. Correlations were investigated between
      POSNA scales, gait parameters, and the Gillette Functional Assessment
      Questionnaire (FAQ) in 63 children (31 males, 32 females; mean age 9.17 years [SD
      3.06], age range 3.75 to 16.44 years) with spastic CP. Twelve participants had
      hemiplegia, 29 diplegia, 12 quadriplegia, and 10 triplegia. The result of
      backwards stepwise multiple regression analysis indicated that the Log normalcy
      index (NI) was a significant predictor of the POSNA Global Function and Comfort
      scale. Energy expenditure (EE) did not add significantly to the prediction. The
      POSNA scales differentiated between the different topographical types of CP. The
      POSNA scale is a valid and useful clinical measure. Used in conjunction with the
      NI, EE, and FAQ, the POSNA scale provides a more complete appraisal of change in
      functioning.

PMID- 12005322
TI  - Worster-drought and congenital bilateral perisylvian syndromes.

PMID- 12005323
TI  - A review of the efficacy of lower-limb orthoses used for cerebral palsy.

PMID- 12005324
TI  - Comments on a recent study of therapeutic electrical stimulation in cerebral
      palsy.

PMID- 12005325
TI  - Urinary problems following acute transverse myelitis in children.

PMID- 12005326
TI  - Intervening factors in caregivers' assessments of pain in non-communicating
      children.

PMID- 12005327
TI  - Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am
      Main area, Germany.
AB  - Herpes simplex virus (HSV) types 1 and 2 are widespread human infectious agents
      that are responsible for persistent and latent infections. HSV type 2 (HSV-2)
      infection is usually transmitted sexually, while HSV type I (HSV-1) is commonly
      acquired by saliva contact during childhood. In a retrospective study, sera from
      more than 4,800 patients were analyzed for HSV type-specific IgG antibodies. In
      people older than 15 years, the seroprevalence of HSV-1 showed no statistically
      significant discrepancy between the control group (76.3% in females and 75.2% in
      males), HIV-infected patients (82.8% in females and 84.3% in males), and organ
      transplant (OTX) recipients (90.3% in females and 86.3% in males) (P>0.05). Age
      related analysis of the control group showed that there is an age-dependent
      increase of HSV-1 seroprevalence in both sexes, reaching its peak in those aged
      40 years and older (women 85.4%, men 82.8%). The only age group in which there is
      a significantly higher seropositivity rate in women than in men is in those aged
      between 15 and 39 years, with 70.8% versus 63.7% (P<0.05). As with HSV-1, there
      is an age-related increase of the HSV-2 seroprevalence; however, this increase
      starts later in life, with the onset of sexual activity. The HSV-2 prevalence
      across all age groups was highest in female prostitutes (78.0%) and among HIV
      infected patients (women 64.1%, men 54.3%); this contrasts with the control group
      (overall women 17%, men 12.5%; those above 15 years of age, women 18%, men 13.8%)
      and the OTX patients (women 22.6%, men 9.8%). In the control group the rate of
      positivity increases with age and peaks in the group older than 40 years (24.2%
      in women and 16.2% in men). In females the seroprevalence is always elevated
      compared with males. The data presented show that female sex and older age are
      independent predictors of HSV-2 seropositivity, while immunosuppression is not.
      Our additional data show no evidence of a statistically significant humoral HSV
      1/HSV-2 cross-immunity. People with HSV-1 serum antibodies have no lower risk of
      HSV-2 seropositivity than those lacking antibodies to HSV-1. The same is true
      when investigating HSV-1 seroprevalence rates in HSV-2-seropositive or -negative
      individuals, retrospectively.

PMID- 12005328
TI  - Quantitation of the spliced late gene of human cytomegalovirus and its kinetics
      during experimental infection.
AB  - Human cytomegalovirus (hCMV) infection is still a cause of morbidity and
      mortality after solid organ and bone marrow transplantation and in other
      immunocompromised states. 'Preemptive therapy' strategies necessitate sensitive
      and specific methods for rapid diagnosis of symptomatic hCMV infection and
      monitoring of antiviral treatment. For analysis of the lytic stage of viral
      replication, the molecular determination of late transcripts is a useful approach
      for diagnosis of hCMV disease. In the present study we established an absolute
      quantitation of hCMV spliced late gene (SLG) RNA transcripts by real-time reverse
      transcription-polymerase chain reaction. Intron spanning primers were used for
      amplification to discriminate between viral DNA and cDNA. For standardization of
      the varying amounts of cDNA analyzed, cytoplasmic beta2-microglobulin (beta2-MG)
      cDNA was quantitated in parallel. cDNA copy numbers of both target sequences
      could be quantitated in a wide linear range from 10 to 10(7) copies. To
      investigate the applicability of the developed assay, diploid lung fibroblasts
      were infected with the virus strain AD169. SLG expression was measured during a
      48-h period after inoculation. After an only low expression during the first 10 h
      (approximately 5 x 10(2) copies/sample or SLG/beta2-MG ratio <0.001), SLG
      transcription increased dramatically after 24 h, peaking at 5x104 copies/sample
      or SLG/beta2-MG ratio of 0.035 after 48 h. Intra- and interassay variability was
      less than 5% for calibrators and less than 10% samples. We conclude that
      quantitation of SLG transcripts by the presented method might be a powerful tool
      for differentiating between hCMV latency and active replication in vitro end in
      vivo, and thus may be a promising tool for diagnosis of symptomatic hCMV
      infection and monitoring of antiviral treatment.

PMID- 12005329
TI  - Antibodies against vaccine-preventable diseases in pregnant women and their
      offspring in the eastern part of Germany.
AB  - Maternal and cord blood samples of 290 pregnant women in the eastern part of
      Germany with a mean age of 28 years (16-41 years) were analyzed for antibodies to
      vaccine-preventable diseases. Both mothers and infants had detectable levels of
      antibodies to mumps in 96% and to tetanus in 93% of cases. Detectable levels to
      poliomyelitis, diphtheria, measles and rubella varied from 55% to 91%. Cord blood
      samples had a significantly higher prevalence of antibodies to pertussis (61%)
      and diphtheria (81%) in comparison to maternal samples (pertussis 37%, diphtheria
      70%) as well as significantly enhanced antibody concentrations to diphtheria. In
      conclusion, the prevalence of antibodies to pertussis (61%), diphtheria (81 %),
      poliomyelitis (55-59%) and measles (85%) is suggested to be insufficient in
      newborn infants to protect them against these infectious diseases.

PMID- 12005330
TI  - Enhancement of pentylenetetrazole-induced seizures by Shigella dysenteriae in LPS
      resistant C3H/HeJ mice: role of the host response.
AB  - Convulsions and encephalopathy are common complications of Shiga toxin (Stx)
      producing Shigella and enterohemorrhagic Escherichia coli infections. In previous
      studies, we demonstrated that Stx and lipopolysaccharide (LPS) act in concert to
      enhance mice sensitivity to pentylenetetrazole (PTZ)-induced seizures via
      mechanisms involving tumor necrosis factor alpha (TNFalpha), interleukinl beta
      and nitric oxide. To further elucidate the role of the host response in Shigella
      related seizures, we studied the ability of Shigella dysenteriae and its products
      to modulate seizures in C3H/HeJ (lps(d/d)) and in C3H/HeN (lps(n/n) mice.
      Injection of S. dysenteriae 60R sonicate elevated plasma TNFalpha and enhanced
      the convulsive response to PTZ in both mouse strains. Induced TNFalpha levels
      were markedly lower in LPS-hyporesponsive C3H/HeJ mice than in LPS- responsive
      C3H/HeN mice: 7.4 ng/ml vs 44 ng/ml (induced by 4LD50). Accordingly, a higher
      dose of S. dysenteriae sonicate was needed to sensitize the C3H/HeJ mice to
      seizures. Stx or LPS alone did not enhance seizures in either strain. Stx
      together with LPS enhanced seizures in LPS-responsive mice, but not in LPS
      hyporesponsive mice in which they induced only a minor elevation in TNFalpha
      levels (1.5 ng/ml). As compared to LPS-responsive mice, the LPS-hyporesponsive
      mice were less susceptible to the lethal effects of Shigella sonicate and were
      resistant to the lethal effect of purified Stx with LPS. These results
      demonstrate the crucial role of the host response with regard to the sensitivity
      to to LPS, and specifically TNFalpha production, in Shigella lethality and
      Shigella-related seizures.

PMID- 12005331
TI  - The immunogenicity of Mycobacterium paratuberculosis 85B antigen.
AB  - Mycobacterium paratuberculosis (MPT) is the etiological agent of
      paratuberculosis. The disease is prevalent throughout the world, and exacts a
      heavy financial toll. At present, the only means of controlling this disease are
      culling or vaccination. The existing vaccines are not very efficient and produce
      a long-lasting local reaction at the point of injection and induce anti
      bodies/delayed-type hypersensitivity (DTH) reaction that cannot be differentiated
      from those of naturally infected animals. New potent acellular vaccines that
      allow discrimination between infected and vaccinated animals are necessary to
      improve the control of this disease. We have isolated, overexpressed and purified
      the 85B antigen of MPT, and characterized the immune response induced by this
      antigen in mice. Our results showed that the recombinant MPT 85B (rMPT 85B)
      antigen induced a high production of interferon (IFN)gamma, interleukin (IL)-6,
      IL-10 and nitric oxide (NO). Spleen cells from mice immunized with rMPT 85B in
      Ribi adjuvant produced a higher level of IL-10 and NO than spleen cells of mice
      immunized with rMPT 85B only. In contrast, the addition of Ribi to the
      immunization protocol resulted in a lower amount of IFNgamma released by spleen
      cells. The levels of spleen cells proliferation in mice vaccinated with the rMPT
      85B protein alone or with rMPT 85B with Ribi adjuvant were, respectively, four
      times or five times greater than in the control mice. The Ribi adjuvant induced
      significantly higher anti-85B antibody production of all classes tested and
      increased the IgG1/IgG2a ratio. DTH responses in mice footpads were observed only
      in mice immunized with rMPT 85B emulsified in Ribi. rMPT 85B induced both a Th1
      and Th2 type of immune response with the later slightly more pronounced when the
      vaccination protocol comprised Ribi as an adjuvant. The rMPT 85B antigen elicited
      a strong immune response and can be considered as a potential candidate for a
      future acellular vaccine.

PMID- 12005332
TI  - Molecular approaches to validate disinfectants against human hepatitis B virus.
AB  - Disinfection is an important measure to prevent hepatitis B virus (HBV)
      transmission by instruments. However, virucidal testing of disinfectants against
      HBV is difficult, because no simple quantitative infectivity assay exists. Since
      molecular changes of viral epitopes and the genome may indicate virus
      inactivation, we measured the alteration of these constituents with 0.065%
      peracetic acid (PAA) for exposure times up to 1 h. Plasma of a chronic HBV
      carrier with 10(9) HBV genomes/ml served as viral source in the form of a 10%
      dilution or of a purified HB-antigen preparation. Alterations of HBV epitopes
      were analyzed with four monoclonal antibodies in an enzyme-linked immunosorbent
      assay. Changes of the HBV genomes were determined by the inability to amplify the
      target sequence with a quantitative real-time polymerase chain reaction, either
      of a short fragment (189 bp) or of the full-length (3,200 bp). The determination
      of the epitope and genome alteration was quantified as log10 reduction factor
      (RF) with the parallel line bioassay. Under a high protein load of 10% human
      plasma, PAA induced a HBV genome alteration of RF = 1.5 after an exposure time of
      60 min. Similar RFs were seen with the four HB epitopes. Without protein load,
      the alteration of these epitopes amounted to a RF of more than 3.5 within 30 min.
      Such inhibition of PAA activity by protein load was also seen in the virucidal
      tests with parvovirus. Although the RF were higher in the virucidal tests, the
      time-dependent dose-response curves for the epitope and genome alteration and for
      the infectivity inactivation followed the same inactivation kinetics. The
      molecular alteration and disintegration epitope and genome test may therefore be
      suitable to measure antiviral activity of disinfectants against HBV.

PMID- 12005333
TI  - Cross-reactivity in flavivirus serology: new implications of an old finding?
AB  - To investigate the influence of pre-existing antibodies against tick-borne
      encephalitis (TBE) or yellow fever (YF) viruses on dengue virus antibody test
      results, we examined sera from vaccinees and from individuals with previous TBE
      virus infection. Distinct IgG antibody cross-reactivity was found in about 15.1%
      in the YF-vaccinated group and in about 9.5% in the TBE-vaccinated group.
      Altogether 15 out of a total of 80 samples tested (18.8%) had detectable dengue
      virus IgG antibody titres. The serum samples from patients with acute TBE virus
      infection not only had the highest anti-TBE virus antibodies but were also highly
      cross-reactive against dengue virus antigens. The high cross-reactivity rate of
      YF and TBE antibody-positive sera in dengue virus antibody assays should be taken
      into account in the interpretation of laboratory tests for the diagnosis of
      flavivirus infections and when undertaking seroepidemiological surveys.

PMID- 12005334
TI  - Neuroimaging in acute stroke.

PMID- 12005335
TI  - Galen (130-201 A.D.): history's most enduring medic.

PMID- 12005336
TI  - Diffusion weighted MR imaging in acute stroke: the SGH experience.
AB  - Cerebrovascular accident (CVA) is a leading cause of death and disability in many
      countries. Diffusion-weighted (DW) magnetic resonance (MR) imaging has been
      reported to be useful in the detection of acute strokes and as an investigative
      tool evaluating the therapeutic effects of neuroprotective and thrombolytic
      agents. The objectives of this study are to share our experience using the
      commercially available isotropic DW scan in imaging of acute stroke, assess its
      usefulness over conventional T2-weighted (T2W) scans in a busy clinical radiology
      unit and highlight it pitfalls. We found the rapid sub-minute DW technique well
      suited for ill and restless stroke patients and superior to T2W scans in many
      ways. It was highly sensitive to acute ischaemic lesions, made lesions easily
      identifiable and readily differentiated the acute lesion from a background of
      multiple chronic infarcts. However, there are potential pitfalls in the
      evaluation of small hyperacute posterior fossa strokes and venous infarcts. The
      major strength of this MR technique lies in its ability to diagnose hyperacute
      strokes and thence the potential for therapeutic thrombolysis, but unfortunately
      patients qualifying for the "therapeutic window" were a minority. More efforts
      need to be focused on public education in order for this powerful imaging
      modality to find its true value and contribute to viability of an effective
      thrombolytic programme.

PMID- 12005337
TI  - Risk factors associated with severe viral croup in hospitalised Malaysian
      children.
AB  - OBJECTIVE: To determine the risk factors associated with severe viral croup in
      hospitalised Malaysian children. METHODOLOGY: The medical records of children
      aged less than five years admitted with a diagnosis of viral croup between 1994
      and 1999 were reviewed. Severe viral croup was diagnosed in children who had
      stridor at rest with marked recession associated with central cyanosis or altered
      level of consciousness. Multivariate logistic regression analysis was performed
      to identify risk factors associated with severe viral croup. RESULTS: Eighteen
      (14.7%) of 122 children with viral croup were severe. These children were older
      (mean age 16.8 +/- 7.2 vs 12.6 +/- 6.6 months, p = 0.01) and had a shorter
      duration of illness prior to admission (1.7 +/- 0.7 days vs 2.3 +/- 1.4 days, p =
      0.03). Age between 12 and 24 months (OR 3.8 95% Cl 1.3, 12.7, p = 0.02) and fever
      (OR 5.7 95% Cl 2.9, 15.6, p = 0.02) were the only risk factors associated with
      severe viral croup after multivariate logistic regression analysis. Only three
      children or 2.5 per 100 children admitted with viral croup required ventilation.
      CONCLUSION: Only a small number of children admitted particularly those between
      12 to 24 months with fever developed severe viral croup. Recognition of these
      risk factors provides a guide in selecting children who will most likely benefit
      from steroid therapy. The overall outcome was nonetheless favourable.

PMID- 12005338
TI  - Public awareness of diabetes mellitus in Singapore.
AB  - INTRODUCTION: Much effort has been devoted to educating the public about
      diabetes. However, the impact of such efforts has yet to be formally evaluated.
      OBJECTIVES: To identify areas of knowledge that might require additional
      educational efforts. METHODOLOGY: A cross-sectional survey was conducted to
      evaluate the general public's knowledge of diabetes. The respondents were
      required to answer 45 questions from a pre-tested questionnaire divided into five
      main sections, namely, general knowledge, risk factors, symptoms and
      complications, treatment and management, monitoring and other miscellaneous
      questions. A point was awarded for each correct response and zero for wrong or
      unsure responses. The maximum total score was 41. The miscellaneous questions
      were not scored. RESULTS: A total of 1337 subjects were interviewed. The mean
      score obtained by the respondents was 66.1% of the maximum possible total score
      (i.e. 27.1 points out of 41). The "correct answer" percentages for the individual
      questions from each section ranges from 22 to 83% (General knowledge), 31 to 91%
      (Risk factors), 48 to 81% (Symptoms and complications), 35 to 87% (Treatment and
      management), and 58 to 93% (Monitoring of condition).With respect to the source
      of medical information, health care professionals did not feature prominently
      (20.7%). CONCLUSION: The public as represented by the samples in this survey is
      generally well informed about diabetes except for a few areas. Analysis of these
      areas would have a significant implication for future public education programme.
      Health care professionals should be more proactive in disseminating health
      information about diabetes to the public.

PMID- 12005339
TI  - Results of Sauve-kapandji procedure.
AB  - INTRODUCTION: Sauve-Kapandji procedure is used to treat distal radioulnar joint
      disorder. MATERIALS AND METHOD: Sixteen patients with distal radioulnar joint
      (DRUJ) disease treated with Sauve-Kapandji procedure between 1996 and 1998 were
      available for review at an average follow up period of 32.8 months,ranging from
      24 to 48 months. The patients were young and the average age at the time of
      procedure was 33.6 years. There were eight cases of post-traumatic DRUJ
      arthritis, two cases of dislocation of DRUJ with malunion of radial fractures and
      six cases of rheumatoid patients with destruction of DRUJ. The distal end of
      ulnar shaft was stabilised with a sling created using radial 1/2 slip of extensor
      carpi ulnaris (ECU) tendon. Functional results were evaluated with Mayo wrist
      score. RESULTS: Fusion of DRUJ was achieved in all cases by two months. Excellent
      results were achieved in eight cases, good in six, fair in one and poor in one.
      All except one case gained increase range of forearm rotation. Complications
      included one case of closure of pseudoarthrosis and required excision of the ulna
      head to restore forearm rotation. CONCLUSION: Sauve-Kapandji procedure is
      recommended in young patients with distal radioulnar joint disorder.

PMID- 12005340
TI  - Laparoscopically-assisted vaginal hysterectomy (LAVH)--an alternative to
      abdominal hysterectomy.
AB  - AIM: To study the outcomes of 42 consecutive patients who were scheduled for a
      laparoscopically-assisted vaginal hysterectomy (LAVH) between I January 1994 to
      31 December 1999. METHOD: Retrospective study RESULTS: Two patients required
      conversion to an abdominal hysterectomy. The range of uteri removed was from six
      to 16 weeks' size. Menorrhagia was the commonest presenting complaint and uterine
      fibroids was the commonest diagnosis. The mean duration of surgery (+/- SD) was
      131.0 +/- 31.7 minutes. Mean blood loss (+/- SD) was estimated at 417 +/- 169
      mls. Six percent of patients required a perioperative blood transfusion. Fifty
      five percent of patients did not require any injectable analgesics and 45% were
      able to ambulate on the day of surgery. The mean duration of hospital stay (+/-
      SD) was 4.2 +/- 2.3 days;The commonest complication was post-operative fever.
      CONCLUSIONS: LAVH patients have a quick postoperative recovery with less pain at
      the expense of a long duration of surgery. LAVH is a feasible option in a
      selected group of patients who would otherwise require an abdominal hysterectomy.

PMID- 12005341
TI  - Medical paternalism serves the patient best.
AB  - It seems obvious that in a post-modern, constructivist world where meaning and
      value systems are often subjective and relative, any absolutist view is likely to
      be questionable. This is more so if it relates to ethics, the foundations,
      interpretation and application of which have been and continue to be much
      debated. So, in addressing the proposition, my efforts were directed at
      identifying a position that would mediate polarity. I examined the contention
      that the doctor, because he is better informed, may claim greater acuity and
      powers of judgment, and its defences against the charge of interfering with
      individual liberty and autonomy through various arguments such as the harm
      principle, the welfare, the principle of legal moralism and the appeal to
      uncertainty. While there is some validity to the arguments proposed, absolute
      paternalism would seem incompatible with respect for individual rights. How
      satisfactory, then, is the paradigm shift from paternalism to the independent
      choice model where the doctor presents neutral statistics as little biased as
      possible by his own views and judgments and leaves the decision making entirely
      to the patient or his/her relatives. This clearly had its limitations too. As
      with much of human experience, the answer would seem to rest in mediating the
      happy mean. Recognising a distinction between autonomy (self-determination) and
      independence (total freedom of choice without any interference) allows for a
      model of qualified independence or "enhanced autonomy" (Quill & Brody, 1996).
      This is predicated on doctor-patient dialogue, exchange of ideas/views,
      negotiation of differences, and sharing power and influence for the common
      purpose of serving the patient's best interest. This model would seem to be a
      responsible and effective approach to management of clinical dilemmas, as well as
      one that in its pluralistic approach is consistent with fundamental moral and
      philosophic propositions. It is by no means flawless, but in an imperfect world,
      there can be no perfect solution; constant negotiation with the realities-
      however uncomfortable--is an inescapable fact of life. Actions are right in
      proportion as they tend to promote happiness: wrong as they tend to produce the
      reverse of happiness. (J S Mil, Utilitarianism) On that supposition, I submit
      that guided paternalism is arguably what serves the patient best.

PMID- 12005342
TI  - Deconstructing paternalism--what serves the patient best?
AB  - On the motion that "medical paternalism serves the patient best", this essay
      reviews current arguments on medical paternalism vs. patient autonomy. Citing
      medico-ethical texts and journals and selected real-life applications like
      electroconvulsive therapy (ECT) and the advanced medical directive (AMD), the
      essay argues that medical paternalism cannot serve the patient best insofar as
      current debates limit themselves to "who" wields the decision-making power. Such
      debates side-step "what" the patient's best interests are. The essay further
      argues through the case of Traditional Chinese Medicine (TCM), and acupuncture in
      particular, that the current dominant Western school of thought excludes other
      forms of "alternative" treatment through medical paternalism.

PMID- 12005343
TI  - Doctor-patient relationship: from medical paternalism to enhanced autonomy.
AB  - For centuries, physicians have been allowed to interfere and overrule patient's
      preferences with the aim of securing patient benefit or preventing harm. With the
      radical rise in emphasis on individual control and freedom, medical paternalism
      no longer receives unquestioned acceptance by society as the dominant mode for
      decision-making in health care. But neither is a decision-making approach based
      on absolute patient autonomy a satisfactory one. A more ethical and effective
      approach is to enhance a patient's autonomy by advocating a medical beneficence
      that incorporates patients' values and perspectives. This can be achieved through
      a model for shared decision making, acknowledging that though the final choices
      reside ultimately in patients, only through physician beneficence can the patient
      be empowered to make meaningful decisions that serve them best. For such a model
      to function effectively, the restoration of trust in doctor-patient relationship
      and the adoption of patient-centred communication are both crucial.

PMID- 12005344
TI  - Lacrimal sac tumour presenting with blood-stained ocular discharge.
AB  - Malignant epithelial tumours of the lacrimal sac are uncommon. They can mimic
      chronic dacryocystitis or dacryostenosis to cause a delay in diagnosis. The
      presence of a medial canthal lump with blood-stained ocular discharge should
      arouse the suspicion of this diagnosis. The prognosis of lacrimal sac tumour is
      often guarded especially following tumour recurrence after incomplete resection.
      We report a patient with squamous cell carcinoma of the lacrimal sac to highlight
      its presentation and clinical course.

PMID- 12005345
TI  - Self-enucleation in a young schizophrenic patient--a case report.
AB  - Self-enucleation represents an extreme but fortunately rare form of deliberate
      self-harm. Case reports of patients who self-enucleate reveal some common
      features. A case of auto-enucleation in a young schizophrenic patient and a short
      discussion on deliberate self-harm are presented.

PMID- 12005346
TI  - Clinics in diagnostic imaging (71). Left iliopsoas abscess secondary to vertebral
      osteomyelitis.
AB  - A 26-year-old woman presented with a progressively painful lump at her left groin
      and upper thigh for five months. She also had intermittent back pain for three
      years. Radiographs and CT showed osteolytic destruction of the several contiguous
      thoracolumbar vertebrae with a large left iliopsoas abscess that extended to
      involve the left gluteus maximus and adductor magnus muscles. She responded well
      to a course of antibiotics. The role of imaging and imaging features of iliopsoas
      abscesses are discussed, together

PMID- 12005347
TI  - Biphasic effects of exogenous phospholipase D on vessel tone.
AB  - There exists functional significance for agonists stimulated phospholipase D
      (PLD) and exogenous PLD in different systems, but the functional importance of
      PLD on vessel tone is not clear. We studied the functional importance of PLD in
      whole animals and in isolated vessel preparation. In in vivo study, we
      demonstrated that intravenous injection of PLD at 10, 30, and 100 units to male
      Sprague-Dawley rats did not significantly alter the mean arterial blood pressure
      and heart rate in 30 minutes. However, in a denuded vessel preparation, PLD from
      10(-3) units/ml to 10 units/ml induced vasoconstriction from 2.8 +/- 1.7 % to
      30.5 +/- 1.7 % of maximal KCI contraction in calcium enriched physiological salt
      solution (PSS). This vasoconstrictive effects of PLD were significantly inhibited
      by omission of extracellular calcium from PSS or by pretreatment the vessels with
      nifedipine (10(-6) M). Pretreated the denuded vessels with a protein kinase C
      inhibitor, chelerythrine (10(-6) M), did not significantly alter the
      vasoconstrictive effects of PLD. These results indicate that calcium channel
      rather than protein kinase C activation is involved in PLD-induced
      vasoconstriction. In endothelium-intact vessels, application of PLD from 10(-4)
      units/ml to 10 units/ml induced endothelium dependent relaxation in vessels
      precontracted with phenylephrine (10(-6) M). This relaxation effects of PLD were
      inhibited by pretreatment of vessels with indomethacin (10(-5) M) or with N-nitro
      L-arginine (L-NAME, 10(-4) M), suggesting prostaglandin and nitric oxide released
      by PLD stimulation. The biphasic effects of PLD on vessel tone are mediated by
      extracellular calcium and by endothelium-derived nitric oxide and prostaglandin.

PMID- 12005348
TI  - Anatomical and functional study of localization of originating neurons of the
      parasympathetic nerve to gallbladder in rabbit brain stem.
AB  - The present study was to investigate the localization of preganglionic
      parasympathetic neurons of gallbladder in brain stem by anatomical and functional
      approaches. Male or female rabbits (n = 11) were anesthetized with sodium
      pentobarbital (30 mg/kg, i.v.). Cholera toxin B conjugated to horseradish
      peroxidase (CB-HRP) was injected into the gallbladder wall. Four days later,
      animals were re-anesthetized and perfused transcardially with paraformaldehyde
      solution in a 0.1 M phosphate buffer. The rabbit brain was then frozenly
      sectioned. The sections were processed for HRP label and stained with neutral
      red. Another group of rabbits (n = 54) were anesthetized by urethane (1 g/kg)
      after fasting for 18-24 hours, Gallbladder pressure (GP) was measured by
      inserting a frog bladder filled with normal saline into the gallbladder.
      Myoelectrical activity of the sphincter of Oddi (SO) was induced by a pair of
      copper electrodes. A glass tube (30 microm tip diameter) connected with a
      microsyringe was directed to the dorsal vagal complex (DVC) for microinjection.
      Majority of retrogradely labeled cells was found bilaterally in dorsal motor
      nucleus of the vagus nerve (DMV) throughout the length, except the rostral and
      caudal part. These cells were distributed in subnuclei parvicellularis or
      mediocellularis of DMV. Some labeled perikarya located in the medial subnucleus
      of the solitary tract (mNTS). Thyrotropin-releasing hormone (TRH, 1.3 mmol/L, 0.2
      microl) microinjected into the rostral portion of the DVC (including DMV and NTS)
      enhanced the motility of gallbladder and SO. Microinjection of TRH at the middle
      part of DVC seldom induces excitatory effects on the gallbladder or SO. TRH
      microinjected into the caudal portion of the DVC elicited weaker response of
      gallbladder and SO than rostral portion. Our results indicated that DMV is one of
      the most important original nuclei of gallbladder's vagus nerves and mNTS may be
      also involved in the control of gallbladder's parasympathetic activity. Neurons
      that innervate the gallbladder distribute at most part of DVC, and are relatively
      dense at rostral and caudal position of DMV.

PMID- 12005349
TI  - Endothelin-1 in citric acid aerosol inhalation-induced airway constriction of
      guinea pigs.
AB  - Endotheline-1 (ET-1) has been shown to enhance tachykinin-induced airway
      constriction. This study was designed to test whether ET-1 is involved in citric
      acid-induced bronchoconstriction. Forty-eight anesthetized-paralyzed guinea pigs
      were divided into six groups of 8 animals each: saline control; citric acid; ET
      1; ET-1 + citric acid; BQ123 + ET-1 + citric acid; and BQ788 + ET-1 + citric
      acid. BQ123 and BQ788 are specific ETA and ETB receptor antagonists,
      respectively. Each animal in the saline control group received 50 breaths of 4 ml
      saline aerosol and in all citric acid-treated groups was given 50 breaths of 4 ml
      aerosol generated from 0.6 M citric acid. In all ET-1-treated groups, each animal
      was exposed to aerosol generated from 10(-8) M ET-1. The animal in the ET-1 +
      citric acid group was exposed to ET-1 5 min prior to the citric acid. For the
      last two groups, each animal was first exposed to aerosol generated from either
      10(-5) M BQ123 or 10(-5) M BQ788. Five min later, the animal was exposed to ET-1;
      and then 5 min later was followed by citric acid. Dynamic respiratory compliance
      (Crs), forced expiratory volume in 0.1 sec (FEV(0.1)), and maximal expiratory
      flow at 30% total lung capacity (Vmax 30) were obtained before and 3-15 min after
      citric acid. Either citric acid or ET-1 inhalation caused significant decreases
      in Crs, FEV(0.1), and Vmax 30, indicating airway constriction. Citric acid
      induced airway constriction, for most cases, was not significantly augmented by
      ET-1. However, either BQ123 or BQ 788 significantly attenuated the airway
      constriction induced by the combination of ET-1 and citric acid. Also, in an
      additional study, either BQ123 or BQ788 significantly attenuated citric acid
      induced airway constriction. These data suggest that endogenous ET-1 plays an
      important role in citric acid aerosol-induced airway constriction in guinea pigs.

PMID- 12005350
TI  - Novel effect of CP55,940, a CB1/CB2 cannabinoid receptor agonist, on
      intracellular free Ca2+ levels in bladder cancer cells.
AB  - The study was undertaken to explore the effect of CP55,940 ((-)-cis-3-[2-Hydroxy4
      (1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol), a drug
      commonly used as a CB1/CB2 cannabinoid receptor agonist, on intracellular free
      Ca2+ levels ([Ca2+]i) in several cell types [Ca2+]i was measured in suspended
      cells by using the fluorescent dye fura-2 as an indicator. At concentrations
      between 1-50 microM, CP55,940 increased [Ca2+]i in a concentration-dependent
      manner with an EC50 of 8 microM. The [Ca2+]i signal comprised an initial rise, a
      slow decay, and a sustained phase. CP55940 (10 microM)-induced (Ca2+]i signal was
      not altered by 5 microM of two cannabinoid receptor antagonists (AM-251, N
      (Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide; AM-281, 1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-m3thyl-N-4
      morpholinyl-1H-pyrazole-3-carboxamide). Extracellular Ca2+ removal decreased the
      maximum value of the Ca2+ signals by 50%. CPS5,940 (10 microM)-induced [Ca2+]i
      increase in Ca2+-free medium was inhibited by 80% by pretreatment with 1 microM
      thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor. Conversely,
      pretreatment with 10 microM CP55,940 in Ca2+-free medium for 6 min abolished
      thapsigargin-induced [Ca2+]i increase. Nifedipine (10 microM) and verapamil (10
      microM) did not alter CP55,940 (10 microM)-induced [Ca2+]i increase. CP55, 940
      (10 microM)-induced Ca2+ release was not affected when phospholipase C was
      inhibited by 2 microM U73122 (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17
      yl)amino)hexyl)-1H-pyrrole-2,5-dione). CP55,940 (5 microM) also increased [Ca22+]
      in Madin-Darby canine kidney cells, MG63 human osteosarcoma cells, and IMR-32
      neuroblastoma cells. Collectively, CP,55940 induced significant [Ca2+]i increases
      in several cell types by releasing store Ca2+ from thapsigargin-sensitive pools
      and by causing Ca2+ entry. The CP55,940's action appears to be dissociated from
      stimulation of cannabinoid receptors

PMID- 12005351
TI  - Coexistence of neurons integrating urinary bladder activity and pelvic nerve
      activity in the same cardiovascular areas of the pontomedulla in cats.
AB  - The present study examines the coexistence of neurons in the same cardiovascular
      point of the pontomedulla that integrates urinary bladder (UB) motility, and
      pelvic nerve activity (PNA). Microinjection of monosodium L-glutamate (Glu) into
      the locus coeruleus (LC), the gigantocellular tegmental field (FTG), the rostral
      ventrolateral medulla (RVLM), and the dorsomedial medulla (DM) produced pressor
      responses, whereas injection into the lateral tegmental field (FTL), the nucleus
      of tractus solitarii (NTS), and the caudal ventrolateral medulla (CVLM) produced
      depressor responses. However, microinjection of Glu into the dorsomotor nucleus
      of the vagus (DMV) and the ambiguus nucleus (AN), where the vagus nerve
      originates, produced marked bradycardia. Many of these cardiovascular responses
      were accompanied by increased, or decreased parasympathetic PNA. In six animals,
      sympathetic renal nerve activity (RNA) and PNA also increased simultaneously
      during the pressor response. The present study also examines the connection
      between the DMV-AN and the sacral intermediolateral column (IML), where
      parasympathetic preganglionic neurons (PGNs) of the pelvic nerve located.
      Biotinylated dextran amine (BDA), an anterograde tracer, was iontophoretically
      injected into the DMV or AN. No labelled terminal or neuron was detected in the
      sacral IML, but labelled terminals were observed in the bilateral LC, and also in
      the bilateral sides of the FTG, FTL, RVLM, DM, and CVLM. These results suggest
      that neurons of the DMV and/or AN may indirectly regulate the sacral
      parasympathetic PGNs through the LC for supraspinal control of the pelvic nerve.
      Furthermore, these results also suggest the coexistence of multiple autonomic
      integrating mechanisms of different kinds within various cardiovascular areas of
      the pontomedulla.

PMID- 12005352
TI  - Absent effect of zinc deficiency on the oxidative stress of erythrocytes in
      chronic uremic rats.
AB  - Both anemia and zinc deficiency are commonly observed in patients with chronic
      uremia. Oxidative stress of red blood cells (RBC) has been suggested to
      participate in the development of anemia in these patients with chronic uremia
      due to reduced life span of RBC. Whether zinc deficiency aggravates the effect of
      oxidative stress on RBC of chronic uremia is still not understood. We thus
      performed the study to determine the influence of zinc deficiency on the
      oxidative stress of RBC in uremic rats. Zinc deficiency was induced by long-term
      dietary zinc deficiency. Five-sixth nephrectomy (5/6 Nx) was used to produce
      chronic uremia. Experiment was carried out in the following five groups: normal
      control (NL), chronic uremia (Nx), chronic uremia + dietary zinc deficiency (Nx
      D), Nx-D + zinc supplement (Nx-DZ) and Chronic uremia + pair-fed (Nx-PF). Osmotic
      fragility and lipid peroxidation of RBC were used to evaluate the oxidative
      stress of RBC. Five weeks after 5/6 nephrectomy (Nx), 5/6 Nx rats present a
      syndrome of uremia to elevate the levels of plasma creatinine and urea, and
      reduce the level of plasma zinc (1.12 +/- 0.08 vs 1.35 +/- 0.05 ug/ml). But they
      does not find to produce anemia and to increase osmotic fragility and lipid
      peroxidation in RBC. Dietary zinc deficiency in Nx-D group produced severe
      anorexia and reduced plasma zinc and selenium levels and the activity of RBC-GPX.
      Yet in Nx-D rats, osmotic fragility and susceptibility of lipid peroxidation in
      red cells did not increase, because of the increase of plasma copper level (1.85
      +/- 0.3 vs 1.41 +/- 0.05 microg/ml) and RBC-SOD activity (1.95 +/- 0.27 vs 0.78
      +/- 0.05 unit/g Hb). Zinc supplement in Nx-D rats (Nx-DZ group) recovered the
      appetite and normalized the levels of plasma zinc, copper and selenium. Food
      restriction in 5/6 Nx rats (Nx-PF group) decreased plasma copper level and
      increased osmotic fragility of RBC and elevated the susceptibility of lipid
      peroxidation after stressing RBC with H2O2 Because Nx-PF rats presented a lower
      RBC-SOD activity (0.44 +/- 0.11 vs 0.78 +/- 0.05 unit/g Hb) and a lower plasma
      copper level. We further found a positive relationship (r=0. 802,p<0.01) between
      plasma copper level and RBC-SOD activity in normal and uremic rats. This study
      suggests that RBC-SOD activity may play an important role in preventing RBC
      oxidative stress. Plasma copper level may be a marker of RBC-SOD activity. We
      conclude, in chronic uremia, zinc deficiency doses not result in RBC oxidative
      stress as plasma copper level is normal, but may affect the absorption of
      intestinal nutrition.

PMID- 12005353
TI  - Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in-vivo.
AB  - Cationic liposomes bind with nucleic acids such as plasmids and
      oligodeoxynucleotides to form complexes known as lipoplexes. Although these
      lipoplexes have several advantages over other forms of nucleic acid transfer
      methods in cell culture and in-vivo, toxicity remains a problem, especially in
      vivo. Nevertheless, these carriers have been used in clinical trials against
      cystic fibrosis and cancer and their usage is attributed mainly to their
      versatility, especially when it comes to the range of routes available for
      administration of nucleic-acid-based drugs in-vivo.

PMID- 12005354
TI  - Evaluation of the inhibition effect of thiolated poly(acrylates) on vaginal
      membrane bound aminopeptidase N and release of the model drug LH-RH.
AB  - The purpose of this study was to evaluate the inhibitory effect of thiolated
      carbopol 974P (carb-cys) on the enzymatic activity of vaginal aminopeptidase N in
      vitro. Mediated by a carbodiimide, L-cysteine was covalently linked to carbopol
      974P. Depending on the weight ratio of polymer to cysteine during the coupling
      reaction, resulting conjugates displayed 31.3-54.4 micromol thiol groups per g
      polymer. The inhibitory effect of carb-cys conjugates was evaluated towards
      isolated aminopeptidase N and aminopeptidase-N-like activity of excised vaginal
      mucosa covered with native mucus, respectively. Enzymatic activity was assayed
      spectrophotometrically using L-leucine-p-nitroanilide (L-leu-pNA) as a synthetic
      substrate. Carb-cys thereby showed a significantly higher inhibitory effect than
      unmodified polymer towards both isolated enzyme and vaginal mucosa. Moreover,
      enzyme inhibition was strongly dependent on the amount of thiol groups being
      immobilised. The more thiol groups available the higher was the inhibitory
      effect. Due to its additional high cohesive properties and the possibility of a
      sustained drug release, which could be shown for the model drug LH-RH, carb-cys
      appears interesting for the development of vaginal peptide drug-delivery systems.

PMID- 12005355
TI  - Enteric-coating capsulation of insulinomimetic vanadyl sulfate enhances
      bioavailability of vanadyl species in rats.
AB  - In recent years, there have been improvements in the treatment of type 2 diabetes
      by oral administration of vanadyl sulfate (VOSO4, VS). The maintenance of vanadyl
      levels in the blood of subjects with type 2 diabetes was found to be important
      for the insulinomimetic activity of VS. However, owing to low bioavailability of
      VS and the development of mild gastrointestinal symptoms and side-effects in some
      subjects, it is necessary to design more effective and safer dosages of VS. After
      discovering that VS is absorbed more thoroughly at the ileum than at other
      gastrointestinal sites, we investigated the absorption processes following oral
      administration of VS by preparing enteric-coated capsules (ECC). Although Cmax
      values were unchanged by the dosage forms, Tmax and MRT values associated with
      the enteric-coating capsulation were prolonged when compared with those observed
      with use of gelatin capsules (GC). An important finding was that the
      bioavailability of VS from ECC (9.8%) was almost double that of VS from either GC
      (4.0%) or the solution (4.8%). Administration of VS-containing ECC to diabetic
      patients is proposed to improve vanadyl absorption over that achieved by the
      administration of either GC or the solution.

PMID- 12005356
TI  - Estimation of cyclodextrin affinity to steroids.
AB  - A nonlinear spectrometric method for determination of the stability constant (Ks)
      for cyclodextrin complex with steroid was developed. The method is based on
      calculation of the parameters of competitive cyclodextrin complexation by
      simultaneous fitting of two types of curves. Those of the first type are the
      dependencies of absorbance of methyl orange solution on the cyclodextrin
      concentration, the second type being the absorption curves of displacement of the
      dye, by steroid, from the cyclodextrin complex. With the method proposed, Ks
      values were calculated with standard deviation less than 10%. This method is
      validated by determination of Ks values using the phase-solubility technique. For
      neutral steroid molecules, the effect of pH on Ks was found to be insignificant.
      Ks values for the cyclodextrin-dye complex were determined for randomly
      methylated beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, carboxymethyl
      beta-cyclodextrin and sulfobutylether-beta-cyclodextrin. More hydrophobic
      steroids were characterised by higher Ks values. Anionic beta-cyclodextrins
      showed high affinity for the steroids studied. Simple equipment and sufficient
      computing allowed recommendation of the method for express estimation of
      cyclodextrin's affinity for hydrophobic substrates.

PMID- 12005357
TI  - Isobolographic analysis of the analgesic interactions between ketamine and
      tramadol.
AB  - Owing to different mechanisms of analgesia, we hypothesized that the combination
      of ketamine and tramadol could produce synergistic or additive antinociceptive
      effects. Swiss albino mice were administered intraperitoneally with ketamine,
      tramadol, a combination of ketamine and tramadol, or saline, and the resulting
      antinociceptive effects were tested in the mouse tail-flick and formalin tests.
      The potencies of the two drugs alone or in combination were obtained by fitting
      data to the Sigmoid Emax equation. Isobolographic analysis was performed to
      evaluate the interaction. CNS depression was also monitored. Results showed that
      tramadol exhibited apparent dose-dependent effects in the tail-flick test, and in
      phase 1 and phase 2 of the formalin test. Ketamine dose-dependently inhibited the
      phase 2 responses, but failed to modify the phase 1 and tail-flick responses.
      Combination of tramadol and ketamine produced significant synergistic
      interactions only in phase 2 of the formalin test (P < 0.05). The synergistic
      combinations also displayed less CNS depression than when an equianalgesic dose
      of ketamine was administered alone. We conclude that in the acute thermal or
      chemical pain model, ketamine is not effective and the net effect of ketamine and
      tramadol in combination was simply additive after systemic administration.
      However, the coadministration produced synergistic antinociception in the
      chemical-induced persistent pain model.

PMID- 12005358
TI  - Concentration-dependent disposition of glucuronide metabolite of valproate.
AB  - The glucuronide conjugation metabolism of valproate (VPA) has been assessed to be
      non-linear within the therapeutic concentration range. However, disposition of
      its metabolite, valproic acid glucuronide (VPAG), in relation to VPA doses is
      unclear. The purpose of this study was to elucidate the characteristics of dose
      related disposition of VPAG. Guinea-pigs were treated with an intravenous bolus
      dose of sodium valproate at 20, 100, 500 or 600 mg kg(-1). Plasma was sampled on
      a pre-selected time schedule, and bile and urine were collected. Concentrations
      of VPA and VPAG in plasma, bile and urine were determined by gas chromatography.
      The pharmacokinetics of VPA and VPAG both were dose-dependent. However, the
      plasma concentration-time profiles of VPAG and VPA were not parallel. At a usual
      dose of VPA (20 mg kg(-1)), plasma VPAG declined with plasma VPA, whereas at a
      high dose of VPA (>500mg kg(-1)), plasma VPAG was elevated against the decline of
      plasma VPA, which suggested accumulation of plasma VPAG possibly owing to
      saturated elimination. The biliary and urinary clearances of VPA (vCLb and vCLu)
      were independent of dose. However, the clearances of plasma VPA (vCLp), plasma
      VPAG (gCLp), biliary and urinary VPAG (gCLb and gCLu) all were decreased against
      the increase in VPA doses. The dose-dependent decrease of gCLu (from 3.19 to 1.12
      mL min(-1)) was less pronounced than that of gCLp (from 6.72 to 0.86 mL min(-1))
      and the gCLu turned to exceed the gCLp at high doses of VPA (> 500 mg kg(-1)).
      These results suggest that the excess urinary VPAG might be produced in kidney.
      In conclusion, at a high dose of VPA, plasma VPAG is accumulated. The
      concentration-dependent biliary and urinary recovery of VPAG might be governed by
      a saturable elimination process rather than by saturable hepatic
      biotransformation rate. Glucuronide conjugation metabolism of VPA in kidney is
      speculated, which might be minor at low levels of plasma VPA, but more obvious
      after saturation of hepatic glucuronidation.

PMID- 12005359
TI  - Multiple dose pharmacokinetics of fiduxosin under fasting conditions in healthy
      elderly male subjects.
AB  - Selective alpha1a-adrenoceptor antagonists are effective agents for treatment of
      benign prostatic hyperplasia, a disorder occurring in middle-aged and elderly
      males. The objective of this study was to determine the pharmacokinetics of
      fiduxosin, a novel alpha1a-adrenoceptor antagonist, following multiple dose
      administration. This was carried out in a Phase I, randomized, double-blind,
      placebo-controlled, parallel group, multiple oral dose study of fiduxosin. Single
      once-daily oral doses of 30, 60, 90 or 120 mg of fiduxosin or placebo were
      administered to healthy elderly male subjects (n = 48; 8 active and 4 placebo per
      dosing group) for 14 consecutive days. Fiduxosin plasma concentration-versus-time
      profiles for days 1, 7 and 14 were used to assess fiduxosin pharmacokinetics.
      Steady state was achieved by day 7. At steady-state mean Tmax (time to maximum
      plasma concentration), CL/F (apparent oral clearance) and Vbeta/F (apparent
      volume of distribution) ranges were 1.8-7.8 h, 27.3-47.2 L h(-1) and 846-1399 L,
      respectively. Tmax and VbetaF were independent of dose. Cmax (maximum plasma
      concentration), Cmin (minimum plasma concentration) and AUC24 (area under plasma
      concentration vs time curve from 0 to 24 h) for days 7 and 14 were linearly
      proportional with dose overthe 30-120 mg/day dose range and were unchanged from
      day 7 to day 14. It was concluded that fiduxosin multiple-dose pharmacokinetics
      were dose-independent and time-invariant over the 30-120 mg/day dose range under
      fasting conditions.

PMID- 12005360
TI  - Spirotetrahydronaphthalene analogues of sympathomimetic catecholamines. Synthesis
      and adrenergic activity of 5,6- and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1
      (2H)-3'-piperidines].
AB  - The 5,6- (5a) and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1 (2H)-3'-piperidine]
      (6a) and their N-isopropyl derivatives (5b and 6b), DDSNPs, were synthesized.
      These compounds can be viewed as the result of the combination of the structure
      of the 3-(3,4-dihydroxyphenyl)-piperidine 2a or 2b, with the structure of the
      corresponding 1-(aminomethyl)-5,6-dihydroxy-(3a or 3b) or 1-(aminomethyl)-6,7
      dihydroxy-1,2,3,4-tetrahydronaphthalene (4a or 4b), 1-AMDTNs. The new compounds
      (5a, b and 6a, b) were assayed for their alpha and beta adrenergic properties by
      means of binding experiments and functional tests and the results were compared
      with those obtained for catecholamines 1a, b and the previously described 3-(3,4
      dihydroxyphenyl)piperidine (3-DPP; 2) and 1-AMDTNs (3, 4). Comparison of the
      affinity and activity data of novel derivatives with those of reference compounds
      2, 3 and 4 shows a general low ability of DDSNPs 5 and 6 to interact with both
      alpha and beta- adrenoceptors.

PMID- 12005361
TI  - Pharmaceutical quality of different Ginkgo biloba brands.
AB  - Ginkgo biloba-containing brands are one of the top sellers within the growing
      market for herbal remedies in many European countries as well as in the USA. In
      the consumers' interest, these brands should feature a certain quality and should
      be transparent in quality claims. In this investigation, a variety of products on
      the USA market was studied with respect to pharmaceutical quality, such as
      quantity of constituents and in-vitro dissolution. In terms of the content of
      active substances, flavone glycosides ranged from 24% to 36% and terpene lactones
      from 4% to 11%. With ginkgolic acids, there was a very large range, from < 500
      ppm to about 90000 ppm. Comparing the dissolution rates of terpene lactones and
      flavone glycosides within the single products, most were approximately the same.
      Thus, terpene lactones and flavone glycosides were released from these products
      and dissolved at the same rate in most cases. Furthermore, most of the products
      investigated released more than the required 75% of the content of both
      components within 30 min. However, several products showed clear and relevant
      differences in dissolution rates to the rest (e.g. < 75% within 30 min or even
      less than 25% after 60 min in one case, indicating much poorer pharmaceutical
      quality). Beside the comparability respectively standardisation of the extracts
      used, the in-vitro dissolution of the relevant constituents should be similar to
      other drugs to guarantee comparable in-vivo performance of herbal products. An
      important step in standardising pharmaceutical quality is the pharmacopoeial
      monograph for Ginkgo biloba extract in Germany, standardising the content of
      pharmacologically relevant substances (flavone glycosides 22-27% and
      terpenlactones 5-7%, 2.8-3.4% ginkgolides A, B, C and 2.6-3.2% bilobalide
      thereof). Many of the investigated products, which refer to the German Commission
      E (of the Federal Institute for Drugs and Medicinal Devices) monograph, are not
      in accordance with this specification. Thus, they can not be considered to be
      pharmaceutically equivalent.

PMID- 12005362
TI  - Receptor regulatory properties evident in the molecular similarity of dopamine
      receptor ligands and purine nucleotides.
AB  - Computational studies have revealed similarities in the relative configurations
      of purine nucleotides and ligands for histamine, acetylcholine and adrenergic
      receptors. In common with other G-protein-regulated receptors, dopamine receptors
      are associated with specific changes in nucleotide levels during signal
      transduction processes. The purpose of this study was to investigate molecular
      similarity in dopamine receptor ligands and purine nucleotides. Molecular
      superimposition and fitting data for D1-like receptor ligands identified a
      pharmacophore in the adenine and ribose rings of ATP. D2-like agonists and
      antagonists related to a pharmacophore in the guanine and ribose rings of GTP.
      The results are consistent with the hypothesis that the dopamine receptor family
      may have evolved from receptors for the ATP and GTP nucleotides.

PMID- 12005363
TI  - Stimulatory effect of paeoniflorin on the release of noradrenaline from ileal
      synaptosomes of guinea-pig in-vitro.
AB  - The effect of paeoniflorin (an active principle of Paeoniae Radix, commonly used
      in traditional Chinese medicine) on the release of noradrenaline (norepineprhine)
      from nerve terminals was investigated using guinea-pig isolated ileal
      synaptosomes. Release was determined as the amount of noradrenaline, quantified
      by high-performance liquid chromatography-electrochemical detection, from samples
      incubated with paeoniflorin or vehicle. Paeoniflorin stimulated the release of
      noradrenaline in a concentration-dependent manner without an effect on the level
      of lactate dehydrogenase in the bathing medium. Tetrodotoxin abolished the action
      of paeoniflorin at concentrations sufficient to block sodium channels. The
      depolarizing effect of paeoniflorin on the membrane potential was also
      illustrated by a concentration-dependent increase in the fluorescence of
      bisoxonol. Moreover, the effect of paeoniflorin on bisoxonol fluorescence in
      ileal synaptosomes seems more potent than that of 4-aminopyridine. That
      paeoniflorin causes influx of calcium ions via the depolarization of nerve
      terminals could be considered. The noradrenaline-releasing action of paeoniflorin
      was abolished by removal of calcium chloride from the bathing medium. This action
      of paeoniflorin was also attenuated by Rp-cAMP atconcentrations sufficientto
      inhibitthe action of cyclicAMP. Therefore, paeoniflorin could induce a calcium
      dependent and cyclic-AMP-related release of noradrenaline from sympathetic nerve
      terminals of guinea-pig ileum. Guanethidine inhibited the noradrenaline-releasing
      action of paeoniflorin in a concentration-dependent manner. The effect of
      paeoniflorin on the increase of bisoxonol fluorescence was not modified by
      atropine. Release of noradrenaline by paeoniflorin from noradrenergic nerve
      terminals was characterized. These findings suggest that paeoniflorin can
      stimulate tetrodotoxin-sensitive depolarization of membranes to result in a
      calcium-dependent and cyclic-AMP-related release of noradrenaline from
      noradrenergic nerve terminals.

PMID- 12005364
TI  - Pharmacological properties and SAR of new 1,4-disubstituted piperazine
      derivatives with hypnotic-sedative activity.
AB  - Preparation, pharmacological properties and structure-activity relationships of
      new pyrimidyl-piperazine derivatives, exhibiting sedative and hypnotic activity
      in mice, are reported. The hypnotic activity of the compounds was comparable with
      that of zopiclone (the known hypnotic-sedative agent), their interaction with
      ethanol, however, being much lower. The obtained results suggested that zopiclone
      and pyrimidylpiperazines 2, 4 and 5 exerted their pharmacological activity
      through a different mechanism - zopiclone through the interaction with
      benzodiazepine receptors and compounds 2, 4 and 5 through an unidentified
      molecular target. The pharmacological properties of compound 3 could be the
      result of a mixed mechanism of action, combining the properties of zopiclone and
      those of compounds 2, 4 and 5. A common feature of zopiclone and compounds 2 and
      3 was that, after their systemic administration, independently of mechanism of
      action, together with the hypnotic effect a reduction of the 5-HT turnover in the
      mouse brain was observed. Minimum structural requirements for the hypnotic
      activity were formulated. Structural considerations have shown that removing the
      alpha-carbonyl group did not influence the drug's ability to inhibit the
      locomotor activity. However, it did influence its ability to disturb motor
      coordination or abolish the righting reflex within non-lethal doses.

PMID- 12005365
TI  - Effect of heparinoid on the production of tissue inhibitor of metalloproteinases
      (TIMP)-3 in rheumatoid synovial fibroblasts.
AB  - Heparinoid is one of the major contents of Mobilat widely used as an
      antirheumatic drug. To clarify the precise mechanisms of the antirheumatic effect
      of heparinoid, we investigated its effects on the production of matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)
      from rheumatoid synovial fibroblasts stimulated (or not) with interleukin-1 alpha
      (IL-1alpha) at 100 units mL(-1). The expression of TIMP-3 mRNA was also
      investigated in a similar manner. The production of both MMPs and TIMPs and the
      expression of TIMP-3 mRNA were investigated by western-blot analysis and northern
      blot hybridization, respectively. Under the stimulation of IL-1alpha, heparinoid
      increased the production of TIMP-3 in a concentration-dependent manner, but not
      TIMP-1, TIMP-2, MMP-1 or MMP-3. Heparinoid did not affect the expression of TIMP
      3 mRNA that was increased by the stimulation of IL-1alpha. These findings suggest
      that the anti-rheumatoid effect of heparinoid may be due to increased production
      of TIMP-3. This increase in TIMP-3 may help redress the imbalance between the
      amounts of MMPs and TIMPs as observed in the joint tissues of rheumatoid
      arthritis and osteoarthritis patients.

PMID- 12005366
TI  - Effects of dofetilide on cardiovascular tissues from normo- and hypertensive
      rats.
AB  - The aim was to test whether dofetilide has some potential for use in the
      treatment of heart failure. Dofetilide at < or = 3 x 10(-5) M had no effect on
      the quiescent Wistar Kyoto (WKY) rat aorta, mesenteric and intralobar arteries,
      or the spontaneous contractions of the WKY rat portal vein. Dofetilide at 10(-6)
      to 3 x 10(-5) M relaxed the KCl-contracted aorta. Dofetilide at 10(-9)-10(-7) M
      augmented the force of contraction of leftventricle strips from 12- and 18-month
      old WKY rats at 2 Hz. Spontaneously hypertensive rats (SHRs) at 12 and 17-21
      months of age are models of cardiac hypertrophy and failure, respectively. The
      augmentation of force at 2 Hz with dofetilide was similar on 12- and 18-month-old
      WKY rats and 12-month-old SHRs but reduced on the 18-month-old SHR left
      ventricle. At a higher more physiological frequency, 4 Hz, the threshold
      concentration of dofetilide required to augment the force responses of 21-month
      old SHR left ventricles was markedly increased and the maximum augmenting effect
      was decreased. Dofetilide at 10(-7)-10(-5) M reduced the rate of the 17-month-old
      WKY rat right atrium, and had a similar effect on age-matched SHR right atrium.
      In summary, dofetilide is a positive inotrope and negative chronotrope in the
      rat. However, as the positive inotropic effect is not observed with clinically
      relevant concentrations at a physiological rate in heart failure, dofetilide is
      unlikely to be useful as a positive inotrope in the treatment of heart failure.

PMID- 12005367
TI  - Synthesis and spasmolytic action of 2-substituted thienopyrimidin-4-one
      derivatives.
AB  - In the search for novel compounds to treat disorders of smooth muscle function,
      efforts have focused on some 2-substituted thieno[2,3-d]pyrimidin-4-one
      derivatives that show interesting spasmolytic action. Our laboratories have
      developed a new series of quaternary salts of 2-substituted thieno[2,3
      d]pyrimidin-4-one and thieno[3,2-d]pyrimidin-4-one isomers with therapeutic
      potential. Thesesubstances were prepared starting from simple derivatives of
      thiophene. Their spasmolytic activity was evaluated on transmurally stimulated
      guinea-pig ileum. The most active compounds (IC50 1.12-2.71 microM) 7f-7h, 12d
      and 12f had the terminal piperidino nucleus in the thioalkyl chain and lacked two
      methyl groups in the thiophene ring. Their relaxant activity on the isolated
      ileum was potentiated (approx. 20-25%) by phosphodiesterase inhibitors. Compounds
      7f-h, 12d and 12f were less effective in inhibiting contractions of the guinea
      pig ileum induced by acetylcholine (IC50 26.7-41.4 microM) or histamine (IC50
      41.5-63.4 microM) and had a moderate binding activity to muscarinic receptors in
      membrane homogenates from the rat heart (M2 sites; pKi values between 5.55+/-0.08
      and 5.14+/-0.12; n = 3) and submaxillary gland (M3 sites; pKi values between
      6.15+/-0.07 and 5.76+/-0.08; n = 3). Action involving soluble guanylyl cyclase or
      any potential binding to guinea-pig ventricular L-type calcium channels was not
      considered likely. It is concluded that at least two different mechanisms of
      action contribute to their spasmolytic activity.

PMID- 12005368
TI  - Distribution of domperidone into the rat brain is increased by brain ischaemia or
      treatment with the P-glycoprotein inhibitor verapamil.
AB  - Domperidone (DOM), a peripheral dopamine D2 receptor antagonist, is a substrate
      of P-glycoprotein (P-gp). Therefore, the transport of DOM into the brain may be
      restricted by P-gp function at the blood-brain barrier, and when the function of
      P-gp is impaired by ATP depletion under conditions of brain ischaemia (e.g.
      cerebral thrombosis), side-effects may be induced as a result of increased
      distribution of DOM into the brain. In this study, we investigated the effects of
      brain ischaemia and verapamil, a P-gp inhibitor, on the permeability coefficient
      surface area product (PS values) of DOM across the blood-brain barrier by using
      an in-situ rat brain perfusion technique. The PS values of DOM were increased 3.4
      and 3.6-fold after brain ischaemia for 10 and 20 min, respectively. Furthermore,
      co-administration of verapamil significantly increased the PS values of DOM by
      42.6- and 43.3-fold in the normal and ischaemia groups, respectively. Brain
      vascular volume was not affected by ischaemia or verapamil. These results show
      that the transport of DOM into the brain is restricted by P-gp and that the brain
      distribution of DOM can be increased by cerebral ischaemia or co-administration
      of a P-gp inhibitor.

PMID- 12005370
TI  - Top challenges for the new dentist.

PMID- 12005369
TI  - California's oral health grade remains mediocre.

PMID- 12005371
TI  - Orderly practice transfer and ethical obligation.

PMID- 12005372
TI  - Patients, pockets, pathogens: new approaches to periodontal management.

PMID- 12005373
TI  - Host modulation: conceptualization to clinical trials and integration into
      clinical practice.
AB  - A better understanding of the pathogenesis of periodontitis has resulted in
      pharmacotherapeutic advancements, addressing both the microbes and the host
      response, leading to improved management of this chronic progressive disease by
      the dental practitioner. The adjunctive use of host-modulatory agents can enhance
      therapeutic responses, slow the progression of the disease, and allow for more
      predictable management of patients. This article will review the pathogenesis and
      risk factors associated with periodontitis and address in detail the concept and
      clinical utility of host modulation as a therapeutic strategy.

PMID- 12005374
TI  - The ins and outs of periodontal antimicrobial therapy.
AB  - A multifaceted antimicrobial approach is necessary for the successful management
      of destructive periodontal disease. Effective antimicrobial periodontal therapy
      aims to overwhelm periodontal pathogens with aggressive initial therapy and
      prevent previously suppressed pathogens from rising up anew through daily oral
      hygiene measures and frequent professional cleaning. Current antimicrobial
      periodontal therapy employs mechanical debridement performed with and without
      surgery, antibiotics, and antiseptics. Subgingival irrigation with povidone
      iodine at the dentist's office and subgingival irrigation with dilute sodium
      hypochlorite for home-care constitute effective, safe, and affordable periodontal
      antimicrobial therapy. This article describes theoretical and practical
      guidelines for implementing rational and cost-effective antimicrobial principles
      in the management of periodontal disease.

PMID- 12005375
TI  - Periodontal disease and systemic health--what you and your patients need to know.
AB  - For many years, dentists have recognized the importance of dental health to
      general health. Recent research findings point to possible associations between
      chronic oral infections such as periodontitis and systemic health problems. This
      article will review the evidence for some of these associations and explore
      factors that may underlie oral-systemic disease connections.

PMID- 12005376
TI  - Periodontal disease and systemic health--diabetes.
AB  - This article discusses the biologic basis of periodontal disease and diabetes
      mellitus. Following is a consideration of the possibility of a link between
      diabetes and periodontal disease. Mounting evidence suggests that there is,
      indeed, a connection between periodontal disease and diabetes.

PMID- 12005377
TI  - As good as it gets.

PMID- 12005378
TI  - Committed compliance, moral self, and internalization: a mediational model.
AB  - Previous research has established that children's committed, eager, willing
      compliance with maternal control promotes moral internalization, whereas their
      opposition interferes with internalization; but the causal mechanism responsible
      for those links is unknown. A mediational model is tested in which committed
      compliance and opposition are seen as influencing the child's emerging view of
      self on moral dimensions, and this "moral self," in turn, regulates moral
      conduct. Committed compliance and opposition were observed in naturalistic mother
      child discipline contexts involving "do" and "don't" demands at 14, 22, 33, and
      45 months. An interactive interview and observations were used to measure the
      moral self and internalization at 56 months (N = 74). The mediational model,
      involving committed compliance and opposition in the "don't" demand context, was
      supported, but only for boys.

PMID- 12005379
TI  - Conditions under which young children can hold two rules in mind and inhibit a
      prepotent response.
AB  - The day-night task requires saying "night" to a picture of the sun and "day" to a
      picture of the moon. In this investigation of why young children fail at this
      task, systematic variations of the task were administered to 96 children, half 4
      years old and half 4 1/2 years old. Training children on the strategy of chunking
      the 2 rules into I ("say the opposite"), thus reducing memory load, did not help
      their performance. What helped was reducing the inhibitory demand by instructing
      them to say "dog" and "pig" (not "night" and "day") even though memory of 2 rules
      and inhibiting saying what the pictures represented were still required. Here the
      response to be activated and the response to be inhibited were unrelated. When
      the correct response was semantically related to, and the direct opposite of, the
      to-be-inhibited response, children performed poorly. Inserting a delay between
      stimulus and response helped even though that delay was filled with distraction.
      Young children apparently need several seconds to compute the answer on this
      task. Often they do not take the needed time; when forced to do so, they do well.

PMID- 12005380
TI  - Development of selective attention: perceptual load influences early versus late
      attentional selection in children and adults.
AB  - The moderating effect of perceptual load on visual selective attention was
      examined in 2 studies. In Study 1, children and young adults searched displays of
      varying set size flanked by irrelevant distractors. Children's performance was as
      efficient as adults' under conditions of high but not low loads, suggesting that
      early selection engages rapidly maturing neural systems and late selection
      engages later-maturing systems. In Study 2, 4 age groups were tested, and place
      markers were set at empty locations to examine perceptual grouping effects. Study
      1's pattem was replicated in all age groups, with onset of early selection
      occurring at lower loads for younger children. Overall, children initiated early
      selection at lower loads to compensate for immature anterior-system interference
      control processes.

PMID- 12005381
TI  - How do preschool children feel about themselves? Unraveling measurement and
      multidimensional self-concept structure.
AB  - Theoretical models suggest that 4- and 5-year-old children should be able to
      differentiate between multiple dimensions of self-concept, but empirical support
      is limited. A new 38-item Self Description Questionnaire for Preschoolers (SDQP)
      that measures 6 self-concept factors (Physical, Appearance, Peers, Parents,
      Verbal, and Math) was developed and tested. Through an individual-interview
      procedure, young children (4.0-5.6 years) completed the SDQP and achievement
      tests. The self-concept scales were reliable (.75-.89), first-order and higher
      order confirmatory factor analysis models fit the data, and factor correlations
      were mostly moderate (-.03-.73; Mdn = .29). Achievement test scores correlated
      modestly with academic self-concept factors (rs = .15-40) but were
      nonsignificantly or significantly negatively related to nonacademic self
      concepts. The results contribute to the critical debate about the validity of
      self-reports for preschool children, who distinguished between multiple
      dimensions of self-concept at an even younger age than suggested by previous self
      concept research.

PMID- 12005382
TI  - Heterosexual risk behaviors in at-risk young men from early adolescence to young
      adulthood: prevalence, prediction, and association with STD contraction.
AB  - Health-compromising lifestyles involve stable patterns of behavior and are
      associated with high-risk social environments and accelerated developmental
      trajectories. Developmentally, antisocial behavior is associated with such
      lifestyles. Mediational models predicting a measure of lifetime average sexual
      risk behavior assessed over a 10-year period (from ages 13-14 to 22-23 years)
      were examined for a sample of at-risk young men. The measure included years of
      abstinence from intercourse as well as levels of 3 key heterosexual indicators of
      risk: frequency of intercourse, number of intercourse partners, and condom use.
      Predictors included lifetime average measures of contextual, family, and peer
      process variables and individual behaviors. In addition, similar models for
      prediction of STD contraction were assessed. A younger age of onset of
      intercourse was associated with higher numbers of intercourse partners after
      onset. As hypothesized, findings indicated mediational associations of
      socioeconomic status, parental monitoring, deviant-peer association, antisocial
      behavior, and substance use in the prediction of sexual risk behavior. Lower
      condom use also predicted STD contraction.

PMID- 12005383
TI  - The Spanish ser/estar distinction in bilingual children's reasoning about human
      psychological characteristics.
AB  - Children's reasoning about the stability of human psychological characteristics
      was investigated in relation to the obligatory distinction between the Spanish
      verb forms ser and estar (which convey different information about the stability
      of characteristics) and the corresponding English form to be. Participants (85
      bilingual children, ages 6 to 10 years) were interviewed to determine (a) whether
      the ser/estar distinction is relevant to reasoning about the stability of human
      characteristics and (b) whether beliefs about the stability of psychological
      characteristics relate to differences in the use of ser and estar to describe and
      explain social events. Children treated ser and to be as more likely than estar
      to convey the stability of psychological characteristics. Children who tended to
      endorse stable views of psychological characteristics were especially likely to
      use the ser form in their descriptions and explanations.

PMID- 12005384
TI  - The relation between hiding skill and judgment of eye direction in preschool
      children.
AB  - This study examines J. H. Flavell, S. G. Shipstead, and K. Croft's (1978) finding
      that 2 1/2-year-old children can hide an object behind a screen but cannot
      achieve the same result by placing the screen in front of the object. Experiment
      1 replicated this finding alongside a task in which children judged what a person
      in a picture was looking at. Performance on the move-object task approached
      ceiling; performances on the move-screen and looking-where tasks were highly
      correlated even after age and control task performance were partialed out (r =
      .54, p < .01). Experiment 2 examined whether the finding resulted because the
      object was more interesting to manipulate than the screen. The move-object task
      remained easier than the move-screen task with an interesting screen and a dull
      object. The move-screen task again correlated specifically with the looking-where
      task. Results are explained in terms of engagement, a precursor to a mature
      understanding of attention.

PMID- 12005385
TI  - Source-monitoring training facilitates preschoolers' eyewitness memory
      performance.
AB  - Preschool children are more susceptible to misleading postevent information than
      are older children and adults. One reason for young children's suggestibility is
      their failure to monitor the source of their memories, as in, for example,
      discriminating whether an event was seen live versus on television. The authors
      investigated whether source-monitoring training would decrease preschoolers'
      suggestibility. Thirty-six 3-4-year-olds observed target live and video events
      and were then given source-monitoring or recognition (control) training on
      nontarget events. Following training, all children answered 24 misleading and
      nonmisleading target-event questions. Children given source-monitoring training
      were more accurate than control group children in response to misleading and
      nonmisleading yes-no questions and in response to nonmisleading, open-ended
      questions. Implications for strategy development, dual representation, and child
      witness interviewing are discussed.

PMID- 12005386
TI  - Development of gaze aversion as disengagement from visual information.
AB  - Older children, but not younger children, were found to look away more from the
      face of an interlocutor when answering difficult as opposed to easy questions.
      Similar results were found in earlier work with adults, who often avert their
      gaze during cognitively difficult tasks (A. M. Glenberg, J. L. Schroeder, & D. A.
      Robertson, 1998). Twenty-five 8-year-olds and 26 5-year-olds answered verbal
      reasoning and arithmetic questions of varying difficulty. The older children
      increased gaze aversion from the face of the adult questioner in response to both
      difficult verbal reasoning questions and difficult arithmetic questions. In
      contrast, younger children (5-year-olds) responded less consistently to cognitive
      difficulty. It is concluded that adultlike patterns of gaze aversion in response
      to cognitive difficulty are certainly acquired by 8 years of age. The
      implications of appropriate gaze aversion for children's management of cognitive
      processing resources are considered.

PMID- 12005387
TI  - Heterogeneity among peer-rejected boys across middle childhood: developmental
      pathways of social behavior.
AB  - The purpose of this longitudinal study was to identify subgroups of rejected boys
      with different developmental pathways of aggression and prosocial behavior across
      the elementary school years. Peer, teacher, and parent reports and behavior
      observations yielded composite scores for aggression and prosocial behavior at 3
      measurement waves. A cluster analysis with these composites on 87 initially
      rejected boys identified 4 subgroups with different developmental pathways of
      prosocial behavior and aggression that were associated with different patterns of
      sociometric acceptance and rejection over time and with social emotional
      adjustment in the last measurement wave. Changes in acceptance and rejection tend
      to precede changes in aggression and prosocial behavior. Cluster differences on
      social emotional adjustment indicators converged into I moderately discriminating
      factor, Social Maladaptation in Peer-Oriented Behavior.

PMID- 12005388
TI  - Analysis of homozygous deletion of the p16 gene and correlation with survival in
      patients with glioblastoma multiforme.
AB  - OBJECT: One of the most frequent genetic abnormalities found in patients with
      glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor
      gene. The authors investigated whether this deletion is associated with prognosis
      in patients with GBM. METHODS: In 46 adult patients with supratentorial GBM,
      homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex
      polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46
      patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional
      hazard regression analysis, adjusted for age at surgery, the Karnofsky
      Performance Scale score, extent of resection, and the MIB-1 labeling index.
      revealed that homozygous deletion of the p16 gene was significantly associated
      with overall survival and progression-free survival in men, but not in women.
      CONCLUSIONS: The results of this study suggest that p16 homozygous deletion is a
      significant unfavorable prognostic factor in male patients with GBM.

PMID- 12005389
TI  - Stereotactic radiosurgery for the treatment of dural arteriovenous fistulas
      involving the transverse-sigmoid sinus.
AB  - OBJECT: The aim of this study was to assess the efficacy and safety of
      radiosurgery for the treatment of dural arteriovenous fistulas (DAVFs) located in
      the region of the transverse-sigmoid sinus. METHODS: A series of 20 patients with
      DAVFs located in the transverse-sigmoid sinus, who were treated with gamma knife
      surgery between June 1995 and June 2000, was evaluated. According to the Cognard
      classification, the DAVF was Type I in four patients. Type IIa in seven, Type IIb
      in two, and combined Type IIa+b in seven. Nine patients had previously been
      treated with surgery and/or embolization, whereas 11 patients underwent
      radiosurgery alone. Radiosurgery was performed using multiple-isocenter
      irradiation of the delineated DAVF nidus. The target volume ranged from 1.7 to
      40.7 cm3. The margin dose delivered to the nidus ranged from 16.5 to 19 Gy at a
      50 to 70% isodose level. Nineteen patients were available for follow-up review,
      the duration of which ranged from 6 to 58 months (median 19 months). Of the 19
      patients, 14 (74%) were cured of their symptoms. At follow up, magnetic resonance
      imaging and/or angiography demonstrated complete obliteration of the DAVF in 11
      patients (58%), subtotal obliteration (95% reduction of the nidus) in three
      (16%), and partial obliteration in another five (26%). There was no neurological
      complication related to the treatment. One patient experienced a recurrence of
      the DAVF 18 months after angiographic confirmation of total obliteration, and
      underwent a second course of radiosurgery. CONCLUSIONS: Stereotactic radiosurgery
      provides a safe and effective option for the treatment of DAVFs involving the
      transverse and sigmoid sinuses. For some aggressive DAVFs with extensive
      retrograde cortical venous drainage, however, a combination of endovascular
      embolization and surgery may be necessary.

PMID- 12005390
TI  - Multicenter study of the feasibility and safety of using the memotherm carotid
      arterial stent for extracranial carotid artery stenosis.
AB  - OBJECT: Carotid artery (CA) angioplasty with stent placement has been proposed as
      an alternative technique for revascularization in cases of CA stenosis. In this
      report the authors review the results of a multicenter Phase I study in which
      they evaluated the safety and feasibility of using a new self-expanding nitinol
      stent, the Bard Memotherm, to treat CA stenosis. METHODS: Enrollment was limited
      to patients in whom there was either 50% or greater symptomatic or 70% or greater
      asymptomatic stenosis of the internal CA. The primary endpoint was a technically
      successful implantation procedure (delivery of the stent to the target site and
      retrieval of the delivery device), resulting in less than 30% residual stenosis
      demonstrated on immediate postprocedure (control) angiograms, and no incidence of
      mortality, ipsilateral stroke, Q-wave myocardial infarction, or other major
      cardiovascular events immediately after or within 30 days following the
      procedure. Stent placement was attempted for 73 lesions in 71 patients (mean age
      71.3 +/- 8.5 years), 43 (61%) of whom were men. The mean degree of stenosis was
      82.6 +/- 9%. The stenosis was symptomatic in 27 (37%) and asymptomatic in 46
      (63%) of 73 lesions. In four procedures the stent could not be delivered or
      released. The mean residual stenosis observed on angiograms was 3.8 +/- 6.9% in
      the 69 lesions treated with the Bard Memotherm stent; residual stenosis was
      greater than 30% in one of the 69 procedures. The primary endpoint was achieved
      in 65 (89%) of the 73 procedures. One patient experienced a major ischemic stroke
      and another patient died of intracerebral hemorrhage. The overall 1-month stroke
      rate was 2.7% for 73 attempted procedures. One patient died of pneumonia and
      acute respiratory distress syndrome, which occurred 3 weeks after the stent
      procedure and was unrelated to the procedure. CONCLUSIONS: The Memotherm stent
      can be used to treat patients with CA stenosis and is associated with a low peri
      procedure complication rate. Long-term follow-up studies are underway to
      determine the impact of stent placement on the risk of ipsilateral ischemic
      events.

PMID- 12005391
TI  - Long-term pallidal deep brain stimulation in patients with advanced Parkinson
      disease: 1-year follow-up study.
AB  - OBJECT: The goal of this study was to investigate the efficacy of long-term deep
      brain stimulation (DBS) of the posteroventral lateral globus pallidus internus
      (GPi) accomplished using a single-contact monopolar electrode in patients with
      advanced Parkinson disease (PD). METHODS: Sixteen patients suffering from severe
      PD and levodopa-induced side effects such as dyskinesias and on-off fluctuations
      were enrolled in a prospective study protocol. There were six women and 10 men
      and their mean age at surgery was 65 years. All patients underwent implantation
      of a monopolar electrode in the posteroventral lateral GPi. Initially, nine
      patients received unilateral stimulation. Three of these patients underwent
      contralateral surgery at a later time. Ten patients received bilateral
      stimulation (contemporaneous bilateral surgery was performed in seven patients
      and staged bilateral surgery in the three patients who had received unilateral
      stimulation initially). Formal assessments were performed during both off
      medication and on-medication (levodopa) periods preoperatively, and at 3 and 12
      months postoperatively. There were no serious complications related to surgery or
      to DBS. Two transient adverse events occurred: in one patient a small pallidal
      hematoma developed, resulting in a prolonged micropallidotomy effect, and in
      another patient a subcutaneous hemorrhage occurred at the site of the pacemaker.
      In patients who received unilateral DBS, the Unified Parkinson's Disease Rating
      Scale activities of daily living (ADL) score during the off-levodopa period
      decreased from 30.8 at baseline to 20.4 at 3 months (34% improvement) and 20.6 at
      12 months (33% improvement) postoperatively. The motor score during the off
      period improved from 57.2 at baseline to 35.2 at 3 months (38% improvement) and
      35.3 at 12 months (38% improvement) postoperatively. Bilateral DBS resulted in a
      reduction in the ADL score during the off period from 34.9 at baseline to 22.3 at
      3 months (36% improvement) and 22.9 at 12 months (34% improvement). The motor
      score for the off period changed from 63.4 at baseline to 40.3 at 3 months (36%
      improvement) and 37.5 at 12 months (41% improvement). In addition, there were
      significant improvements in patients' symptoms during the on period and in on-off
      motor fluctuations. CONCLUSIONS: Pallidal DBS accomplished using a monopolar
      electrode is a safe and effective procedure for treatment of advanced PD.
      Compared with pallidotomy, the advantages of pallidal DBS lie in its
      reversibility and the option to perform bilateral surgery in one session.
      Comparative studies in which DBS is applied to other targets are needed.

PMID- 12005392
TI  - Optimal location of thalamotomy lesions for tremor associated with Parkinson
      disease: a probabilistic analysis based on postoperative magnetic resonance
      imaging and an integrated digital atlas.
AB  - OBJECT: Renewed interest in stereotactic neurosurgery for movement disorders has
      led to numerous reports of clinical outcomes associated with different treatment
      strategies. Nevertheless, there is a paucity of autopsy and imaging data that can
      be used to describe the optimal size and location of lesions or the location of
      implantable stimulators. In this study the authors correlated the clinical
      efficacy of stereotactic thalamotomy for tremor with precise anatomical
      localization by using postoperative magnetic resonance (MR) imaging and an
      integrated deformable digital atlas of subcortical structures. METHODS: Thirty
      one lesions were created by stereotactic thalamotomy in 25 patients with tremor
      dominant Parkinson disease. Lesion volume and configuration were evaluated by
      reviewing early postoperative MR images and were correlated with excellent, good,
      or fair tremor outcome categories. To allow valid comparisons of configurations
      of lesions with respect to cytoarchitectonic thalamic boundaries, the MR image
      obtained in each patient was nonlinearly deformed into a standardized MR imaging
      space, which included an integrated atlas of the basal ganglia and thalamus. The
      volume and precise location of lesions associated with different clinical
      outcomes were compared using nonparametric statistical methods. Probabilistic
      maps of lesions in each tremor outcome category were generated and compared.
      Statistically significant differences in lesion location between excellent and
      good. and excellent and fair outcome categories were demonstrated. On average,
      lesions associated with excellent outcomes involved thalamic areas located more
      posteriorly than sites affected by lesions in the other two outcome groups.
      Subtraction analysis revealed that lesions correlated with excellent outcomes
      necessarily involved the interface of the nucleus ventralis intermedius (Vim;
      also known as the ventral lateral posterior nucleus [VLp]) and the nucleus
      ventrocaudalis (Vc; also known as the ventral posterior [VP] nucleus).
      Differences in lesion volume among outcome groups did not achieve statistical
      significance. CONCLUSIONS: Anatomical evaluation of lesions within a standardized
      MR image-atlas integrated reference space is a useful method for determining
      optimal lesion localization. The results of an analysis of probabilistic maps
      indicates that optimal relief of tremor is associated with lesions involving the
      Vim (VLp) and the anterior Vc (VP).

PMID- 12005393
TI  - Vertebral artery-posterior inferior cerebellar artery bypass with a superficial
      temporal artery graft to treat aneurysms involving the posterior inferior
      cerebellar artery.
AB  - OBJECT: In patients with aneurysms that require occlusion of the posterior
      inferior cerebellar artery (PICA), revascularization of this artery should be
      performed. A novel surgical method for revascularization of the PICA is
      presented. METHODS: After a segment of the superficial temporal artery (STA) was
      harvested, the aneurysm was treated by trapping, followed by placement of a
      vertebral artery (VA)-PICA bypass in which the STA segment was used as a graft.
      When the length of the proximal PICA was inadequate, the distal end of the STA
      was anastomosed to the proximal PICA in an end-to-side fashion. When the length
      of the proximal PICA was adequate, the STA was anastomosed to the proximal PICA
      in an end-to-end fashion. In either case, the proximal end of the STA was
      anastomosed to the VA in an end-to-side fashion. This procedure was used in nine
      patients whose aneurysms involved the PICA. Although partial lateral medullary
      syndrome developed in one of them, follow-up evaluation revealed graft patency in
      all patients. There were no instances of recurrent hemorrhage or ischemia.
      CONCLUSIONS: Although this procedure requires harvesting of an STA graft and two
      anastomoses, it facilitates anterograde flow to the PICA territory. It also
      involves minimal mobilization of brainstem perforating vessels and the proximal
      PICA.

PMID- 12005394
TI  - Correlation between auditory function and internal auditory canal pressure in
      patients with vestibular schwannomas.
AB  - OBJECT: Hearing loss is the most common presenting symptom in patients who harbor
      a vestibular schwannoma (VS). Although mechanical injury to the cochlear nerve
      and vascular compromise of the auditory apparatus have been proposed, the exact
      mechanism of this hearing loss remains unclear. To test whether pressure on the
      cochlear nerve from tumor growth in the internal auditory canal (IAC) is
      responsible for this clinical finding, the authors prospectively evaluated
      intracanalicular pressure (ICaP) in patients with VS and correlated this with
      preoperative brainstem response. METHODS: In 40 consecutive patients undergoing a
      retrosigmoid-transmeatal approach for tumor excision, ICaP was measured by
      inserting a pressure microsensor into the IAC before any tumor manipulation.
      Pressure recordings were correlated with tumor size and preoperative auditory
      evoked potential (AEP) recordings. The ICaP, which varied widely among patients
      (range 0-45 mm Hg), was significantly elevated in most patients (median 16 mm
      Hg). Although these pressure measurements directly correlated to the extension of
      tumor into the IAC (p = 0.001), they did not correlate to total tumor size (p =
      0.2). In 20 patients in whom baseline AEP recordings were available, the ICaP
      directly correlated to wave V latency (p = 0.0001), suggesting that pressure from
      tumor growth in the IAC may be responsible for hearing loss in these patients.
      CONCLUSIONS: Tumor growth into the IAC results in elevation of ICaP and may play
      a role in hearing loss in patients with VS. The relevance of these findings to
      the surgical treatment of these tumors is discussed.

PMID- 12005395
TI  - Why do chronic subdural hematomas continue to grow slowly and not coagulate? Role
      of thrombomodulin in the mechanism.
AB  - OBJECT: Thrombomodulin is a thrombin receptor on vascular endothelial cells that
      is highly expressed when these cells are injured, and it has anticoagulating
      activity. The authors investigated thrombomodulin expression to clarify why
      chronic subdural hematomas (CSDHs) continue to grow slowly, like a tumor, and are
      liquefied. METHODS: Burr hole craniotomy and drainage were performed in all 35
      patients with CSDH who were included in the study. The plasma-soluble
      thrombomodulin and blood clotting factor values were determined in the hematoma
      and in peripheral blood. In the seven most recent cases, the plasma-soluble
      thrombomodulin values were determined in the residual hematoma collected from the
      drainage tube the day after surgery. The outer membranes of the CSDH that were
      obtained as specimens at operation were stained with monoclonal antibody against
      thrombomodulin for immunohistochemical studies. The plasma-soluble thrombomodulin
      values were higher (p < 0.0001), and conversely the values for factors V and VIII
      were lower in the hematoma than in peripheral blood (p < 0.0001). The plasma
      soluble thrombomodulin values were lower in the residual hematomas than in the
      same lesions at operation (p = 0.018). The endothelial cells on the sinusoidal
      vessels exhibited immunoreactivity with thrombomodulin antibody in 28 (93%) of 30
      cases. CONCLUSIONS: The thrombomodulin is expressed on the sinusoidal vessels,
      and the blood coagulation system is inhibited in the hematoma. These findings
      indicate that these vessels are continuously injured and fail to heal. As a
      result, the bleeding from the sinusoidal vessels may persist, and the hematoma
      may grow slowly and fail to coagulate. It is suspected that transmitted pulsation
      variations in the hematoma cavity generate sinusoidal vessel injury.

PMID- 12005396
TI  - Convection-enhanced delivery into the rat brainstem.
AB  - OBJECT: Convection-enhanced delivery (CED) can be used safely to achieve high
      local infusate concentrations within the brain and spinal cord. The use of CED in
      the brainstem has not been previously reported and may offer an alternative
      method for treating diffuse pontine gliomas. In the present study the authors
      tested CED within the rat brainstem to assess its safety and establish
      distribution parameters. METHODS: Eighteen rats underwent stereotactic cannula
      placement into the pontine nucleus oralis without subsequent infusions. Twenty
      rats underwent stereotactic cannula placement followed by infusion of fluorescein
      isothiocyanate (FITC)-dextran at a constant rate (0.1 microl/minute) until
      various total volumes of infusion (V(i)s) were reached: 0.5, 1, 2, and 4 microl.
      Additional rats underwent FITC-dextran infusion (V, 4 microl) and were observed
      for 48 hours (five animals) or 14 days (five animals). Serial (20-microm thick)
      brain sections were imaged using confocal microscopy with ultraviolet
      illumination, and the volume of distribution (Vd) was calculated using computer
      image analysis. Histological analysis was performed on adjacent sections. No
      animal exhibited a postoperative neurological deficit, and there was no
      histological evidence of tissue disruption. The Vd increased linearly (range 15.4
      55.8 mm3) along with increasing Vi, with statistically significant correlations
      for all groups that were compared (p < 0.022). The Va/Vi ratio ranged from 14 to
      30.9. The maximum cross-sectional area of fluorescence (range 9.8-20.9 mm2) and
      the craniocaudal extent of fluorescence (range 2.8-5.1 mm) increased with
      increasing Vi. CONCLUSIONS: Convection-enhanced delivery can be safely applied to
      the rat brainstem with substantial and predictable V(d)s. This study provides the
      basis for investigating delivery of various candidate agents for the treatment of
      diffuse pontine gliomas.

PMID- 12005397
TI  - Persistent accumulation of cyclooxygenase-1-expressing microglial cells and
      macrophages and transient upregulation by endothelium in human brain injury.
AB  - OBJECT: Secondary damage after central nervous system (CNS) injury is driven in
      part by oxidative stress and CNS inflammation and is substantially mediated by
      cyclooxygenases (COXs). To date, the rapidly inducible COX-2 isoform has been
      primarily linked to inflammatory processes, whereas expression of COX-1 is
      confined to physiological functions. The authors report the differential
      localization of COX-1 in human traumatic brain injury (TBI). METHODS:
      Differential cellular COX-1 protein expression profiles were analyzed following
      TBI in 31 patients and compared with neuropathologically unaltered control brains
      by using immunohistochemistry. In these patients with TBI, a significant increase
      of COX-1 protein expression by vessel endothelial and smooth-muscle cells and
      CD68+ microglia/macrophages was observed to be strictly confined to the lesion.
      Accumulation of COX-1+ microglia/macrophages in the lesion was already evident 6
      hours postinjury, reaching maximal levels after several weeks and remaining
      elevated at submaximal levels for several months after injury. Furthermore, COX
      1+ cell clusters were located in the Virchow-Robin space during the leukocyte
      infiltration period from Days 4 to 8 after TBI. Double-labeling experiments
      confirmed coexpression of COX-1 by CD68+ microglia/macrophages. The numbers of
      COX-1+ vessel endothelial and smooth-muscle cells increased from Day 1, remaining
      at submaximal levels for months after injury. CONCLUSIONS: The prolonged
      accumulation of COX- 1+ microglia/macrophages that were restricted to
      perilesional areas affected by the acute inflammatory response points to a role
      of COX-1 in secondary injury. The authors have identified localized, accumulated
      COX- I expression as a potential pharmacological target following TBI. Their
      results challenge the current paradigms of a selective COX-2 role in the
      postinjury inflammatory response.

PMID- 12005398
TI  - Experimental validation of deuterium oxide-mediated antitumoral activity as it
      relates to apoptosis in murine malignant astrocytoma cells.
AB  - OBJECT: Deuterium oxide (D2O), or heavy water, affects a variety of biological
      activities different from those of water. The authors examined the antitumoral
      effect of D2O on brain neoplasms and demonstrated D2O-mediated cytotoxicity by
      using a Rous sarcoma virus-induced murine malignant astrocytoma cell line, RSVM.
      The mechanism of the observed cytotoxicity may involve D2O-induced apoptosis and
      cell-cycle modulation. METHODS: The authors performed an assay with methylthiazol
      tetrazolium bromide and a trypan blue dye exclusion test to confirm in vitro D2O
      mediated cytotoxicity for RSVM cells. At D2O concentrations of 10 to 50%, the
      cytotoxic effect was dose and time dependent. Flow cytometry analysis revealed
      programmed cell death (apoptosis) and the accumulation of RSVM cells during the
      G2/M phase. By applying the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling method, fluorescein isothiocyanate
      annexin V and propidium iodide double staining, and caspase-family protease
      activity analysis, the authors demonstrated both DNA fragmentation and
      enhancement of caspase activity after a 48-hour treatment with D2O, thus
      indicating that D2O induces apoptosis in RSVM cells. Apoptotic DNA fragmentation
      was completely abolished by the caspase inhibitor Z-VAD-FMK (benzyloxycarbonil
      Val-Ala-Aps-fluoromethylketone). The findings indicate that the caspase
      activation pathway may be involved in D2Oinduced apoptosis. CONCLUSIONS: The
      authors found that D2O is cytotoxic to malignant astrocytoma cells. The mechanism
      of D2O-mediated cytotoxicity involved the induction of apoptosis and cell
      accumulation during the G2/M phase. This D2O-induced apoptosis is modulated
      through the caspase activation pathway.

PMID- 12005399
TI  - Aberrant nuclear factor-kappaB activity and its participation in the growth of
      human malignant astrocytoma.
AB  - OBJECT: It has been suggested that nuclear factor (NF)-kappaB, a pleiotropic
      transcription factor, controls cell proliferation. The authors examined NF-kappaB
      activity and its participation in the growth of human malignant astrocytoma.
      METHODS: The authors examined NF-kappaB activity in human malignant astrocytoma
      cell lines and high-grade astrocytoma tissues by using electrophoretic mobility
      shift assays and immunohistochemical studies, respectively. In addition,
      messenger (m)RNA expression of p50 and RelA, which are representative subunits of
      NF-kappaB, and IkappaBalpha, which is a representative inhibitory protein of NF
      KB, were analyzed using Northern blot hybridization in the astrocytoma cell
      lines. Furthermore, alterations in DNA synthesis and cell growth in the
      astrocytoma cell lines were examined after inhibition of NF-kappaB activity by
      RelA antisense oligodeoxynucleotide. The authors found NF-kappaB activity in all
      astrocytoma cell lines and high-grade astrocytoma tissues that were examined, but
      not in the fetal astrocyte strain or in normal cerebral tissue. Expression of
      p50, RelA, and IkappaBalpha mRNA was found in the fetal astrocyte strain and
      normal adult brain tissue, in addition to the astrocytoma cell lines. The
      relative levels of expression of these mRNAs were similar among these cell lines,
      the cell strain, and normal tissue. The RelA antisense oligodeoxynucleotide
      specifically reduced the levels of RelA mRNA expression and NF-kappaB activity in
      the astrocytoma cell lines, thus significantly inhibiting their DNA synthesis and
      cell growth. CONCLUSIONS: Human malignant astrocytoma cells have aberrant NF-KB
      activity, which promotes their growth. This activity is not associated with
      aberrant expression of p50 and RelA.

PMID- 12005400
TI  - Real-time detection of vascular occlusion and reperfusion of the brain during
      surgery by using infrared imaging.
AB  - OBJECT: Application of sensitive infrared imaging is ideally suited to observe
      blood vessels and blood flow in exposed organs, including the brain. Temporary
      vascular occlusion is an important part of neurosurgery, but the capacity to
      monitor the effects of these occlusions in real time is limited. In surgical
      procedures that require vascular manipulation, such as those involving aneurysms,
      arteriovenous malformations (AVMs), or tumors, the ability to visualize blood
      flow in vessels and their distribution beds would be beneficial. The authors
      recount their experience in the use of a sensitive (0.02 degrees C), high
      resolution (up to 50 microm/pixel) infrared camera with a rapid shutter speed (up
      to 2 msec/frame) for localizing cortical function intraoperatively. They observed
      high-resolution images of cerebral arteries and veins. The authors hypothesized
      that infrared imaging of cerebral arteries, performed using a sensitive, high
      resolution camera during surgery, would permit changes in arterial flow to be be
      seen immediately, thus providing real-time assessment of brain perfusion in the
      involved vascular territory. METHODS: Cynomolgus monkeys underwent extensive
      craniectomies, exposing the frontal, parietal, and temporal lobes. Temporary
      occlusions of the internal carotid artery and middle cerebral artery branches (30
      events) were performed serially and were visualized with the aid of an infrared
      camera. Arteries and veins of the monkey brain were clearly visualized due to
      cooling of the exposed brain, which contrasted with blood within the vessels that
      remained at core temperature. Blood flow changes in vessels were seen immediately
      (< 1 second) in real time during occlusion and reopening of the vessels,
      regardless of the duration of the occlusion. Areas of decreased cortical blood
      flow rapidly cooled (-0.3 to 1.3 degrees C) and reheated in response to
      reperfusion. Rewarming occurred faster in arteries than in the cortex (for a 20
      minute occlusion, the change in temperature per second was 2 x 10(-2) degrees C
      in the artery and 7 x 10(-3) degrees C in the brain). Collateral flow could be
      evaluated by intraoperative observations and data processing. CONCLUSIONS: Use of
      high-resolution, digital infrared imaging permits real-time visualization of
      arterial flow. It has the potential to provide the surgeon with a means to assess
      collateral flow during temporary vessel occlusion and to visualize directly the
      flow in parent arteries or persistent filling of an aneurysm after clipping.
      During surgery for AVMs, the technique may provide a new way to assess arterial
      inflow, venous outflow, results of embolization, collateral flow, steal, and
      normal perfusion pressure breakthrough.

PMID- 12005401
TI  - Axonal regeneration after cold preservation of nerve allografts and
      immunosuppression with tacrolimus in mice.
AB  - OBJECT: The purpose of this study was to combine the immunosuppressive and
      neuroregenerative effects of tacrolimus (FK506) with cold preservation of
      peripheral nerve allografts to maximize axonal regeneration across short
      peripheral nerve gaps. METHODS: Ninety-six male C3H mice were randomized to six
      groups, which were composed of animals with isografts (Group 1, positive
      control), allografts (Group 2, negative control), allografts treated with
      subtherapeutic doses of FK506 without and with cold preservation (Groups 3 and
      4), and allografts treated with therapeutic doses of FK506 without and with cold
      preservation (Groups 5 and 6). Results were determined using walking-track data
      and histomorphometric measurements. Three weeks postoperatively, animals treated
      with therapeutic doses of FK506 after receiving cold-preserved allografts
      demonstrated accelerated functional recovery relative to all other groups. In
      addition, histomorphometric parameters in these animals (1,257 +/- 847 total
      axons, 6.7 +/- 3.3% nerve tissue, 11.8 +/- 6.5% neural debris, 8,844 +/- 4,325
      fibers/mm2 nerve density, and 2.53 +/- 0.25 microm fiber width) were the same as
      or better than in all other groups. The parameters of percent nerve tissue (p <
      0.016), nerve density (p < 0.038), and percent neural debris (p < 0.01) were
      statistically significantly better than those in all other groups, including
      Group 1 (isograft, positive control). CONCLUSIONS: The combination of FK506
      treatment with cold preservation of nerve allografts resulted in functional and
      histomorphometric recovery superior to that with either modality alone.

PMID- 12005402
TI  - Perfusion- and diffusion-weighted magnetic resonance imaging for monitoring
      decompressive craniectomy in animals with experimental hemispheric stroke.
AB  - OBJECT: The aim of this study was to use two types of serial magnetic resonance
      (MR) imaging-perfusion-weighted (PW) and diffusion-weighted (DW)-to monitor
      craniectomy in rats with hemispheric stroke. METHODS: Focal cerebral ischemia was
      induced in 36 rats by using an endovascular method of occlusion of the middle
      cerebral artery (MCAO). Craniectomy was performed 4 or 24 hours later in 12
      animals each. Twelve control animals underwent occlusion but did not receive
      treatment. Perfusion-weighted, DW, and T2-weighted MR images were obtained at 4,
      24, 48, 72, and 168 hours postocclusion in all animals. Relative regional
      cerebral blood volumes and apparent diffusion coefficients (ADCs) were calculated
      for the cortex and basal ganglia. Hemispheric lesion volumes (expressed as
      percentages of total brain volumes; %HLV) as they appeared on DW and T2-weighted
      MR images and on histological slices stained with 2,3,5-triphenyltetrazolium
      chloride were compared. Neurological performances and infarct volumes measured 7
      days postocclusion were used as study end points. Both PW and DW images
      demonstrated ischemic tissue 4 hours after MCAO in all animals. Early treatment
      by performing craniectomy significantly improved cortical perfusion (p < 0.01),
      whereas the same procedure conveyed no benefit to the basal ganglia. Compared
      with findings in control animals, the DW image-derived %HLV was significantly
      reduced (p < 0.01) and the cortical ADCs at 4 and 24 hours postocclusion were
      significantly higher in animals treated early (p < 0.05). Late treatment with
      craniectomy did not significantly affect cerebral perfusion. The correlation
      between the DW imaging-derived %HLV and the histologically derived %HLV at 4 to
      72 hours postocclusion was good (r = 0.74), whereas at Day 7 postocclusion the
      %HLV was underestimated up to 41% on DW imaging. At 4 hours postocclusion T
      weighted imaging failed to demonstrate the ischemic lesion, whereas from 24 to 72
      hours postocclusion the correlation between the T2-weighted imaging-derived %HLV
      and the histologically derived %HLV was good (r > 0.81). Neurological performance
      was significantly improved in animals treated using craniectomy. CONCLUSIONS:
      Early craniectomy significantly improves cortical perfusion through
      leptomeningeal collateral vessels, significantly reduces infarct size, and
      improves neurological performance in animals with experimental acute hemispheric
      infarction. Both PW and DW imaging are suitable for noninvasive monitoring of the
      effects of decompressive craniectomy.

PMID- 12005403
TI  - Management of tumor bed cysts after chemotherapeutic wafer implantation. Report
      of four cases.
AB  - Adjuvant use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers with surgical
      resection is becoming common for the treatment of malignant gliomas. Cyst
      formation in the tumor resection cavity is a recently described complication
      associated with the use of BCNU wafers. There is currently no report in which
      successful management of this complication without additional surgical
      intervention is described. The authors describe four patients in whom
      postoperative cysts developed in the tumor resection cavity after placement of
      BCNU wafers. These include a 38-year-old man with a left frontoparietal tumor, a
      48-year-old man with a right frontal lobe tumor, a 78-year-old man with a left
      parietooccipital tumor, and a 61-year-old woman with a left frontotemporal tumor.
      Histopathological studies of biopsy samples revealed malignant glioma in each
      patient. All four patients had unremarkable perioperative courses, were
      discharged within 3 to 8 days of surgery, and subsequently returned with acute
      neurological deterioration. Follow-up magnetic resonance (MR) imaging
      demonstrated cyst formation with significant mass effect at the previous
      resection site. Three patients were treated with high-dose dexamethasone and
      returned to their neurological baseline over an 8-day period. The fourth patient
      improved after surgical drainage and biopsy sampling of the cyst, which revealed
      no evidence of infection or recurrent tumor, but again sought medical care 2
      weeks later with cyst recurrence necessitating high-dose steroid therapy. On MR
      images at least a 30% reduction in cyst size was demonstrated in all four
      patients, each of whom remained clinically stable at 2, 6, 6, and 4 months of
      follow-up review. Neurosurgeons should be aware of the potential for
      postoperative cyst formation accompanied by clinically significant mass effect
      after BCNU wafer implantation, as well as the potential for successful
      nonsurgical management leading to clinical and radiological improvement.

PMID- 12005404
TI  - Application of recombinant activated factor VII during surgery for a giant skull
      base hemangiopericytoma to achieve safe hemostasis. Case report.
AB  - The authors report on a 64-year-old woman with a huge recurrent skull base
      hemangiopericytoma, in whom they encountered severe difficulty in attaining
      intraoperative hemostasis. Standard surgical hemostatic methods and the
      administration of fresh-frozen plasma and prothrombin complex concentrates failed
      to stop diffuse bleeding from an inoperable tumor remnant. At a critical point
      during the operation, the intravenous administration of recombinant activated
      factor VII, combined with mechanical compression, finally led to satisfactory
      hemostasis. The rationale for using recombinant activated factor VII in
      situations of uncontrolled bleeding during neurosurgical procedures is discussed,
      along with the literature in which the use of recombinant activated factor VII as
      a maneuver of last resort is reported for hemostasis in other surgical fields.

PMID- 12005405
TI  - Self-inflicted vocal cord paralysis in patients with vagus nerve stimulators.
      Report of two cases.
AB  - Vagus nerve stimulation for treatment of epilepsy is considered safe; reports of
      severe complications are rare. The authors report on two developmentally disabled
      patients who experienced vocal cord paralysis weeks after placement of a vagus
      nerve stimulator. In both cases, traction injury to the vagus nerve resulting in
      vocal cord paralysis was caused by rotation of the pulse generator at the
      subclavicular pocket by the patient. Traumatic vagus nerve injury caused by
      patients tampering with their device has never been reported and may be analogous
      to a similar phenomenon reported for cardiac pacemakers in the literature. As the
      use of vagus nerve stimulation becomes widespread it is important to consider the
      potential for this adverse event.

PMID- 12005406
TI  - Intraosseous dural arteriovenous fistula of the skull base associated with
      hearing loss. Case report.
AB  - The most common clinical presentations of dural arteriovenous fistulas (DAVFs)
      are bruit, headache, increased intracranial pressure, and intracranial
      hemorrhage. In particular locations, such as the cavernous sinus or middle
      cranial fossa, cranial nerve involvement due to dural arterial steal or venous
      occlusion may develop. A case in which a DAVF is associated with hearing loss,
      however, has not previously been reported. The authors report a case in which an
      intraosseous DAVF and associated hearing loss probably resulted from cochlear
      nerve or vascular compression caused by the draining vein or nidus of the DAVF.

PMID- 12005407
TI  - Bilateral subdural effusion and cerebral displacement associated with spontaneous
      intracranial hypotension: diagnostic and management strategies. Report of two
      cases.
AB  - The authors describe two patients with bilateral subdural effusion and cerebral
      displacement associated with spontaneous intracranial hypotension (SIH) and
      discuss the possible pathophysiological origins of these abnormalities. The signs
      seen on magnetic resonance imaging in both cases, such as tonsillar descent,
      subdural effusion, meningeal enhancement, downward displacement of the optic
      chiasm, and crowding of this structure and the hypothalamus between the pituitary
      gland and brain, can help to establish the diagnosis of SIH. Therapy with a
      lumbar epidural blood patch resulted in the rapid resolution of all symptoms and
      most morphological abnormalities. The authors propose diagnostic and management
      strategies based on their own experiences and the reported cases of SIH in the
      medical literature.

PMID- 12005408
TI  - Osteosarcoma and fibrosarcoma caused by postoperative radiotherapy for a
      pituitary adenoma. Case report.
AB  - Sarcomatous change is a rare complication of postoperative radiotherapy for
      pituitary adenomas. The authors report on what they believe to be the first case
      in which fibrosarcoma and, later, osteosarcoma developed during a 14-year period
      following surgery and radiotherapy for a nonsecreting pituitary macroadenoma.

PMID- 12005409
TI  - Cherry angiomas associated with familial cerebral cavernous malformations. Case
      illustration.

PMID- 12005410
TI  - Accessory foramen opticum, ovale, and spinosum. Case illustration.

PMID- 12005411
TI  - Internal intracranial encephalocele reduced by a subdural-peritoneal shunt. Case
      illustration.

PMID- 12005412
TI  - Eyebrow incision.

PMID- 12005413
TI  - Papaverine and vasospasm.

PMID- 12005414
TI  - Subarachnoid hemorrhage and atmospheric pressure.

PMID- 12005415
TI  - Clavaspirin, an antibacterial and haemolytic peptide from Styela clava.
AB  - We cloned the precursor of a novel peptide from a cDNA library prepared from
      pharyngeal tissues of the tunicate, Styela clava. Its sequence predicted a
      histidine-rich, amidated 23-residue peptide (FLRF(IG)SVIHGIGHLVHHIGVAL-NH2) that
      we named clavaspirin. A synthetic clavaspirin was prepared and it was found that
      it killed Gram-positive and Gram-negative bacteria, permeabilized the outer and
      inner membranes of Escherichia coli, lysed phosphatidylglycerol (POPG) liposomes,
      and was potently haemolytic towards human and bovine erythrocytes. Each of these
      activities was performed more effectively at an acidic pH. Circular dichroism
      measurements of synthetic clavaspirin revealed a largely alpha-helical structure
      and polarized and residue-specific FTIR spectrometry showed that its association
      with phospholipid membranes was influenced by pH. Peptides such as clavaspirin
      may equip tunicate haemocytes to mediate cytotoxicity and participate in
      antimicrobial defence.

PMID- 12005416
TI  - Effects of Na2SO4 on hydrophobic and electrostatic interactions between
      amphipathic alpha-helices.
AB  - The effects of 2 molal Na2SO4 at neutral pH on hydrophobic and electrostatic
      interactions between amphipathic alpha-helices were investigated by circular
      dichroism spectroscopy. The amphipathic peptides that were studied included LEK
      (acetyl-LEELKKKLEELKKKLEEL-NH2) and LEE (acetyl-LEELEEELEELEEELEEL-NH2). In
      phosphate buffer at neutral pH, only LEK adopted a predominantly alpha-helical
      conformation, attributable to glu-lys+ interactions where a major contribution is
      evidently a hydrogen bond (Biochemistry 32: 9668-9676). Despite the presence of
      lys+ in the e and g' positions of the abcdefg heptad repeat, LEK exhibited mean
      residue ellipticities at 222 nm ([theta]222) which were dependent on peptide
      concentration, indicating the presence of a coiled coil. In the presence of 2
      molal Na2SO4 at 25-75 degrees C, the helical content of LEK increased, with the
      greatest increase observed at 75 degrees C. The value of the ellipticity ratio R
      ([theta]222/[theta]208) of LEK in 2 molal Na2SO4 also increased, indicating a
      stronger interhelical association. At 50 degrees C and 75 degrees C, LEK remained
      predominantly alpha-helical. In phosphate buffer at neutral pH, LEE was mainly
      random coil. In the presence of 2 molal Na2SO4, however, the peptide formed alpha
      helices that associated to form a coiled coil. At 50 degrees C and 75 degrees C,
      LEE became predominantly random coil but the remaining alpha-helices were still
      associating. These results are consistent with the strengthening of interhelical
      hydrophobic interactions and the absence of screening of helix-stabilizing and
      helix-destabilizing electrostatic interactions in amphipathic alpha-helices by
      Na2SO4.

PMID- 12005417
TI  - Measurement of the affinity of melittin for zwitterionic and anionic membranes
      using immobilized lipid biosensors.
AB  - The binding of melittin to zwitterionic dimyristyphosphatidylcholine (DMPC) and
      anionic dimyristylphosphatidylglycerol (DMPG) was analysed using two different
      immobilized model membrane systems. The first system used surface plasmon
      resonance (SPR), which monitors the real-time binding of peptides to an
      immobilized hybrid bilayer. SPR experiments reflected a stronger binding of
      melittin for DMPG than for DMPC, while kinetic analysis suggested the existence
      of at least two distinct binding steps. The second lipid biosensor system
      involved an immobilized phospholipid monolayer covalently attached to a
      microporous silica surface. The binding of melittin to the immobilized monolayer
      was then monitored using dynamic elution chromatography with varied methanol
      concentrations to analyse the binding of melittin to DMPC and DMPG. The nonlinear
      binding behaviour observed for melittin with the phosphatidylcholine (PC) and
      phosphatidylglycerol (PG) monolayers compared with the linear retention plots and
      Gaussian peak shapes observed for the control molecule demonstrated that melittin
      undergoes significant conformational and orientational changes upon binding to
      the immobilized PC and PG ligands. The dependence of log k' on per cent methanol
      also demonstrated a bimodal interaction whereby hydrophobic forces predominated
      at higher temperatures and methanol concentrations, while other forces,
      presumably electrostatic in nature, also made a contribution to the affinity of
      the peptides for the lipid monolayer, particularly at lower temperatures. The
      complementary use of these two lipid biosensors thus allows the role of
      hydrophobic and electrostatic forces in peptide-membrane interactions to be
      studied.

PMID- 12005418
TI  - Designing heterodimeric two-stranded alpha-helical coiled-coils: the effect of
      chain length on protein folding, stability and specificity.
AB  - The E/K coil, a heterodimeric coiled-coil, has been designed as a universal
      peptide capture and delivery system for use in applications such as biosensors
      and affinity chromatography. In this design, heterodimer formation is specified
      through the placement of charged residues at the e and g positions of the heptad
      repeat. The affinity and stability of the E/K coil has been modified in order to
      allow a greater range of conditions for association and dissociation by varying
      the chain length to obtain three, four and five heptad coiled-coils (21, 28 and
      35 residues per polypeptide chain). The effect of chain length on stability and
      folding was examined by circular dichroism spectroscopy, guanidine hydrochloride
      denaturation, and redox equilibrium experiments. It was found that increases in
      chain length produced increases in the stability of heterodimeric coiled-coils,
      but in a nonlinear fashion. The resulting disulfide-bridged heterostranded
      molecules and reduced heterodimers span a wide range of stabilities (deltaG=3.3
      11.9 kcal/mol), greatly expanding their scope for use in protein engineering and
      biomedical applications.

PMID- 12005419
TI  - The use of coiled-coil interactions for the analysis and micropreparative
      isolation of adenomatous polyposis coli protein complexes.
AB  - The coiled coil is a common structural motif found both as the dominant structure
      in fibrous proteins and as an oligomerization domain in a variety of cytoskeletal
      and extracellular matrix proteins. Coiled-coils typically consist of two to four
      helices that are supercoiled around one another in either parallel or
      antiparallel orientations. In the past few years our knowledge of the structure
      and specificity of coiled coil interactions has increased, allowing the de novo
      design and preparation of coiled-coils with well-defined structure and
      specificity. Indeed, the design and synthesis of a peptide that binds
      specifically to a single coiled-coil-containing protein, adenomatous polyposis
      coli (APC) has been reported. We have optimized solid-phase synthesis techniques
      to produce a modified form of the anti-APC peptide that contains a biotin moiety
      specifically placed so as to allow selective orientation onto the surface of a
      biosensor or affinity support. These peptide surfaces have been used to both
      monitor and purify APC and APC complexes from cellular extracts.

PMID- 12005420
TI  - Antibacterial, antitumor and hemolytic activities of alpha-helical antibiotic
      peptide, P18 and its analogs.
AB  - The alpha-helical antibiotic peptide (P18: KWKLFKKIPKFLHLAKKF-NH2) designed from
      the cecropin A(1-8)-magainin 2 (1-12) hybrid displayed strong bactericidal and
      tumoricidal activity without inducing hemolysis. The effect of the Pro9 residue
      at central position of P18 on cell selectivity was investigated by Pro9 --> Leu
      or Pro9 --> Ser substitution. Either substitution markedly reduced the
      antibacterial activity of P18 and increased hemolysis, although it did not
      significantly affect cytotoxicity against human transformed tumor and normal
      fibroblast cells. These results suggest that a proline kink in alpha-helical
      antibiotic peptide P18 serves as a hinge region to facilitate ion channel
      formation on bacterial cell membranes and thus plays an important role in
      providing high selectivity against bacterial cells. Furthermore, to investigate
      the structure-antibiotic activity relationships of P18, a series of N- or C
      terminal deletion and substitution analogs of P18 were synthesized. The C
      terminal region of P18 was related to its antibiotic activity and alpha-helical
      conformation on lipid membranes rather than N-terminal one. Higher alpha-helicity
      of the peptides was involved in the hemolytic and antitumor activity rather than
      antibacterial activity. Except for [L9]-P18 and [S9]-P18, all the designed
      peptides containing a Pro residue showed potent antibacterial activity, although
      they did not induce a cytolytic effect against human erythrocyte and normal
      fibroblast cells at the concentration required to kill bacteria. In particular,
      P18 and some analogs (N-1, N-2, N-3, N-3L and N-4L) with potent bactericidal and
      tumoricidal activity and little or no normal cell toxicity may serve as an
      attractive candidate for the development of novel anti-infective or antitumor
      agents.

PMID- 12005421
TI  - Synthetic peptides from the N-domains of CEACAMs activate neutrophils.
AB  - Four members of the carcinoembryonic antigen family, CEACAM1, CEACAM8, CEACAM6
      and CEACAM3, recognized by CD66a, CD66b, CD66c and CD66d monoclonal antibodies
      (mAb), respectively, are expressed on human neutrophils. CD66a, CD66b, CD66c and
      CD66d mAb binding to neutrophils triggers an activation signal that regulates the
      adhesive activity of CD11/CD18, resulting in an increase in neutrophil adhesion
      to human umbilical vein endothelial cells. Molecular modeling of CEACAM1 using
      IgG and CD4 as models has been performed, and three peptides from the N-terminal
      domain were found to increase neutrophil adhesion to human umbilical vein
      endothelial cell monolayers. The peptides were 14 amino acids in length and were
      predicted to be present at loops and turns between beta-sheets. To better
      understand the amino acid sequences critical for this biological activity, in the
      present study we examined the other neutrophil CEACAMs and the highly homologous
      CEACAM, CEA. Molecular modeling of the N-terminal domains of human CEACAM8, -6, 
      3 and CEA was performed. Twenty peptides, each 14 amino acids in length, that
      were homologous to the previously reported peptides from the N-domains of
      CEACAM1, were synthesized and tested for their ability to alter neutrophil
      adhesion. Only one new peptide, from the N-domain of CEA, was found to increase
      neutrophil adhesion, and this peptide differed from the corresponding CEACAM1
      peptide by only a single conservative amino acid substitution. Importantly, minor
      amino acid differences between active and inactive homologous peptides suggest
      regions of these peptides that are critical for biological activity. The data
      suggest that the regions SMPF of peptide CD66a-1, QLFG of peptide CD66a-2 and
      NRQIV of peptide CD66a-3 are critical for the activities of these peptides, and
      for the native CEACAMs.

PMID- 12005422
TI  - Synthesis of novel protected Nalpha(omega-thioalkyl) amino acid building units
      and their incorporation in backbone cyclic disulfide and thioetheric bridged
      peptides.
AB  - General methods for the preparation of protected Nalpha(omega-thioalkyl) amino
      acids building units for backbone cyclization using reductive alkylation and on
      resin preparation are described. The synthesis of non-Gly Fmoc-protected S
      functionalized N-alkylated amino acids is based on the reaction of readily
      prepared protected omega-thio aldehyde with the appropriate amino acid.
      Preparation of Fmoc-protected S-functionalized N-alkylated Gly building units was
      carried out using two methods: reaction of glyoxylic acid with Acm-thioalkylamine
      and an on-resin reaction of bromoacetyl resin with Trt-thioalkylamines. Three
      model peptides were prepared using these building units. The GlyS2 building unit
      was incorporated into a backbone cyclic analog of somatostatin that contains a
      disulfide bridge. Formation of the disulfide bridge was performed by on-resin
      oxidation using 12 or Tl(CF3COO-)3. Both methods resulted in the desired product
      in a high degree of purity in the crude. The AspS3 building unit was also
      successfully incorporated into a model peptide. In addition, the in situ
      generation of sulfur containing Gly building units was demonstrated on a
      Substance P backbone cyclic analog containing a thioether bridge.

PMID- 12005423
TI  - Disulfide pairing and secondary structure of ASP1, an olfactory-binding protein
      from honeybee (Apis mellifera L).
AB  - In insects, the transport of airborne, hydrophobic odorants and pheromones
      through the sensillum lymph is accomplished by olfactory-binding proteins (CBPs).
      We report the structural characterization of a honeybee OBP called ASP1 found in
      workers and drones, previously observed to bind queen pheromone components. A
      novel method based on ion-spray mass spectrometry analysis of cyanylation-induced
      cleavage products of partially reduced protein with Tris(2-carboxyethyl)phosphine
      was needed to determine the recombinant ASP1 disulfide bond pairing. It was
      observed to be Cys(I)-Cys(III), Cys(II)-Cys(V), Cys(IV)-Cys(VI), similar to those
      already described for other OBPs from honeybee and Bombyx mori suggesting that
      this pattern occurs commonly throughout the diverse family of insect OBPs.
      Circular dichroism revealed that ASP1 is an all-alpha protein in accordance with
      NMR preliminary data, but unlike lipocalin-like vertebrate OBPs.

PMID- 12005424
TI  - Evaluation of the conformational propensities of peptide isosteres as a basis for
      selecting bioactive pseudopeptides.
AB  - Our aim was to compare the repertoires of conformers formed by the model
      zwitterionic peptides AA and AAA in aqueous solution with the conformational
      profiles of a range of their peptide isosteres, so as to facilitate selection of
      isosteres for synthesis and testing as biologically stable surrogates of
      bioactive di- and tripeptides. Comparisons were based upon the results of
      conformational analysis using a random search approach implemented within the
      SYBYL molecular modelling package, using zwitterionic molecules, simulated
      aqueous solvation using a dielectric constant of 80 and allowing all torsions to
      vary. For each compound, individual conformers were grouped on the basis of
      specific combinations of psi, phi and omega torsions and, using their energies,
      the aggregated percentage for each group was calculated using a Boltzmann
      distribution and displayed using a 3D pseudo Ramachandran plot relating
      percentage conformer to psi and phi torsions. Retroamide, N-methylamide and
      thioamide isosteres showed the best match to natural peptides and to the
      molecular recognition parameters defined for substrates of peptide transporters.
      The results should aid rational design of therapeutic agents in various areas,
      e.g. oral delivery of drugs by peptide transporters and of peptidase inhibitors.
      This approach may usefully be applied to various biochemical and pharmaceutical
      topics.

PMID- 12005425
TI  - SUMO wrestling with specificity.
AB  - A new structure reveals how substrates are recognized for conjugation to the
      ubiquitin-like protein SUMO, a posttranslational modification that functions in
      activation of transcription factors, nuclear import, and cell division.

PMID- 12005426
TI  - Chloride channel function: partial charges and dipolar rods.
AB  - The regulated flow of ions across biological membranes is a process fundamental
      to all living organisms. The crystal structures of representative chloride
      channels recently published in Nature, together with the previously determined
      structures of a potassium channel, provide a solid basis for understanding the
      chemical principles that govern selective ion flow.

PMID- 12005427
TI  - Apoptosome: the cellular engine for the activation of caspase-9.
AB  - Characterization of the apoptosome by cryo-EM reveals a wheel-shaped heptameric
      assembly involving Apaf-1 and cytochrome c. This structure provides a framework
      for understanding the activation mechanisms of caspase-9, an important initiator
      caspase in apoptosis.

PMID- 12005428
TI  - The significance of performance ranking in CASP--response to Marti-Renom et al.

PMID- 12005429
TI  - Structural basis for the cyclization of the lipopeptide antibiotic surfactin by
      the thioesterase domain SrfTE.
AB  - Many biologically active natural peptides are synthesized by nonribosomal peptide
      synthetases (NRPS). Product release is accomplished by dedicated thioesterase
      (TE) domains, some of which catalyze an intramolecular cyclization to form
      macrolactone or macrolactam cyclic peptides. The excised 28 kDa SrfTE domain, a
      member of the alpha/beta hydrolase enzyme family, exhibits a distinctive bowl
      shaped hydrophobic cavity that hosts the acylpeptide substrate and tolerates its
      folding to form a cyclic structure. A substrate analog confirms the substrate
      binding site and suggests a mechanism for substrate acylation/deacylation.
      Docking of the peptidyl carrier protein domain immediately preceding SrfTE
      positions the 4'-phosphopantheinyl prosthetic group that transfers the nascent
      acyl-peptide chain to SrfTE. The structure provides a basis for understanding the
      mechanism of acyl-PCP substrate recognition and for the cyclization reaction that
      results in release of the macrolactone cyclic heptapeptide.

PMID- 12005430
TI  - Structure and dynamics of the anticodon arm binding domain of Bacillus
      stearothermophilus Tyrosyl-tRNA synthetase.
AB  - The structure of a recombinant protein, TyrRS(delta4), corresponding to the
      anticodon arm binding domain of Bacillus stearothermophilus tyrosyl-tRNA
      synthetase, has been solved, and its dynamics have been studied by nuclear
      magnetic resonance (NMR). It is the first structure described for such a domain
      of a tyrosyl-tRNA synthetase. It consists of a five-stranded beta sheet, packed
      against two alpha helices on one side and one alpha helix on the other side. A
      large part of the domain is structurally similar to other functionally unrelated
      RNA binding proteins. The basic residues known to be essential for tRNA binding
      and charging are exposed to the solvent on the same face of the molecule. The
      structure of TyrRS(delta4), together with previous mutagenesis data, allows one
      to delineate the region of interaction with tRNATyr.

PMID- 12005431
TI  - The structural basis of localization and signaling by the focal adhesion
      targeting domain.
AB  - The localization of focal adhesion kinase (FAK) to sites of integrin clustering
      initiates downstream signaling. The C-terminal focal adhesion targeting (FAT)
      domain causes this localization by interacting with talin and paxillin. FAT also
      mediates signaling through Grb2 via phosphorylated Y925. We report two crystal
      structures of the FAT domain. Large rearrangements of the structure are indicated
      to allow phosphorylation of Y925 and subsequent interaction with Grb2. Sequence
      homology and structural compatibility suggest a FAT-like fold for the C-terminal
      domains of CAS, Efs/Sin, and HEF1. A structure-based alignment including these
      proteins and the vinculin tail domain reveals a conserved region that could play
      a role in focal adhesion targeting. Previously postulated "paxillin binding
      subdomains" may contribute to structural integrity rather than directly to
      paxillin binding.

PMID- 12005432
TI  - Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a
      prototype for the amino acid kinase enzyme family, during catalysis.
AB  - N-Acetyl-L-glutamate kinase (NAGK), a member of the amino acid kinase family,
      catalyzes the second and frequently controlling step of arginine synthesis. The
      Escherichia coli NAGK crystal structure to 1.5 A resolution reveals a 258-residue
      subunit homodimer nucleated by a central 16-stranded molecular open beta sheet
      sandwiched between alpha helices. In each subunit, AMPPNP, as an alphabetagamma
      phosphate-Mg2+ complex, binds along the sheet C edge, and N-acetyl-L-glutamate
      binds near the dyadic axis with its gamma-COO- aligned at short distance from the
      gamma-phosphoryl, indicating associative phosphoryl transfer assisted by: (1)
      Mg2+ complexation; (2) the positive charges on Lys8, Lys217, and on two helix
      dipoles; and (3) by hydrogen bonding with the y-phosphate. The structural
      resemblance with carbamate kinase and the alignment of the sequences suggest that
      NAGK is a structural and functional prototype for the amino acid kinase family,
      which differs from other acylphosphate-making devices represented by
      phosphoglycerate kinase, acetate kinase, and biotin carboxylase.

PMID- 12005433
TI  - Structure of the DNA-bound T-box domain of human TBX3, a transcription factor
      responsible for ulnar-mammary syndrome.
AB  - T-box genes encode transcription factors involved in morphogenesis and
      organogenesis of vertebrates and invertebrates. Mutations in human T-box genes
      TBX3, TBX5, and TBX1 cause severe genetic disorders known as Ulnar-Mammary
      syndrome (UMS), Holt-Oram syndrome (HOS), and DiGeorge syndrome, respectively.
      The crystal structure of the T-box domain of the first human T-box transcription
      factor, TBX3, in complex with DNA at 1.7 A resolution explains structural
      consequences of T-box domain point mutations observed in UMS and HOS patients.
      Comparison with the structure of the T-box domain from Xenopus laevis (Xbra)
      bound to DNA shows differences in several secondary structure elements and in the
      quaternary structure of the two complexes. TBX3 independently recognizes the two
      binding sites present in the palindromic DNA duplex, whereas in Xbra, binding to
      the palindrome is stabilized through interactions between the two monomers. The
      different quaternary structures suggest different DNA binding modes for T-box
      transcription factors.

PMID- 12005434
TI  - Crystals of peptide deformylase from Plasmodium falciparum reveal critical
      characteristics of the active site for drug design.
AB  - Peptide deformylase catalyzes the deformylation reaction of the amino terminal
      fMet residue of newly synthesized proteins in bacteria, and most likely in
      Plasmodium falciparum, and has therefore been identified as a potential
      antibacterial and antimalarial drug target. The structure of P. falciparum
      peptide deformylase, determined at 2.8 A resolution with ten subunits per
      asymmetric unit, is similar to the bacterial enzyme with the residues involved in
      catalysis, the position of the bound metal ion, and a catalytically important
      water structurally conserved between the two enzymes. However, critical
      differences in the substrate binding region explain the poor affinity of E. coli
      deformylase inhibitors and substrates toward the Plasmodium enzyme. The
      Plasmodium structure serves as a guide for designing novel antimalarials.

PMID- 12005435
TI  - Substrate shape determines specificity of recognition for HIV-1 protease:
      analysis of crystal structures of six substrate complexes.
AB  - The homodimeric HIV-1 protease is the target of some of the most effective
      antiviral AIDS therapy, as it facilitates viral maturation by cleaving ten
      asymmetric and nonhomologous sequences in the Gag and Pol polyproteins. Since the
      specificity of this enzyme is not easily determined from the sequences of these
      cleavage sites alone, we solved the crystal structures of complexes of an
      inactive variant (D25N) of HIV-1 protease with six peptides that correspond to
      the natural substrate cleavage sites. When the protease binds to its substrate
      and buries nearly 1000 A2 of surface area, the symmetry of the protease is
      broken, yet most internal hydrogen bonds and waters are conserved. However, no
      substrate side chain hydrogen bond is conserved. Specificity of HIV-1 protease
      appears to be determined by an asymmetric shape rather than a particular amino
      acid sequence.

PMID- 12005436
TI  - Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from
      the interferon-beta promoter.
AB  - Upon viral infection, NF-kappaB translocates to the nucleus and activates the IFN
      beta gene by binding to the PRDII element. Strikingly, NF-kappaB loses its
      ability to activate the IFN-beta gene when the PRDII element is substituted by
      closely related sites. We report here the crystal structure of NF-kappaB p50/p65
      heterodimer bound to the PRDII element from the IFN-beta promoter. The structure
      reveals an unexpected alteration in configuration, in which the p50 specificity
      domain moves by as much as approximately 9 A when compared to NF-kappaB
      heterodimer bound to the immunoglobulin kappaB site (Ig-kappaB) while maintaining
      the same base-specific contacts with the DNA. Taken together, the structure
      offers new insights into the allosteric effects of closely related DNA sites on
      the configuration of NF-kappaB and its transcriptional selectivity.

PMID- 12005437
TI  - Crystal structure of inositol 1-phosphate synthase from Mycobacterium
      tuberculosis, a key enzyme in phosphatidylinositol synthesis.
AB  - Phosphatidylinositol (PI) is essential for Mycobacterium tuberculosis viability
      and the enzymes involved in the PI biosynthetic pathway are potential
      antimycobacterial agents for which little structural information is available.
      The rate-limiting step in the pathway is the production of (L)-myo-inositol 1
      phosphate from (D)-glucose 6-phosphate, a complex reaction catalyzed by the
      enzyme inositol 1-phosphate synthase. We have determined the crystal structure of
      this enzyme from Mycobacterium tuberculosis (tbINO) at 1.95 A resolution, bound
      to the cofactor NAD+. The active site is located within a deep cleft at the
      junction between two domains. The unexpected presence of a zinc ion here suggests
      a mechanistic difference from the eukaryotic inositol synthases, which are
      stimulated by monovalent cations, that may be exploitable in developing selective
      inhibitors of tbINO.

PMID- 12005438
TI  - Downstream regulator TANK binds to the CD40 recognition site on TRAF3.
AB  - TRAFs (tumor necrosis factor receptor [TNFR]-associated factors) bind to the
      cytoplasmic portion of liganded TNFRs and stimulate activation of NF-kappaB or
      JNK pathways. A modulator of TRAF signaling, TANK, serves as either an enhancer
      or an inhibitor of TRAF-mediated signaling pathways. The crystal structure of a
      region of TANK bound to TRAF3 has been determined and compared to a similar
      CD40/TRAF3 complex. TANK and CD40 bind to the same crevice on TRAF3. The
      recognition motif PxQxT is presented in a boomerang-like structure in TANK that
      is markedly different from the hairpin loop that forms in CD40 upon binding to
      TRAF3. Critical TANK contact residues were confirmed by mutagenesis to be
      required for binding to TRAF3 or TRAF2. Binding affinity, measured by isothermal
      titration calorimetry and competition assays, demonstrated that TANK competes
      with CD40 for the TRAF binding site.

PMID- 12005439
TI  - Structural milestones in the reaction pathway of an amide hydrolase: substrate,
      acyl, and product complexes of cephalothin with AmpC beta-lactamase.
AB  - Beta-lactamases hydrolyze beta-lactam antibiotics and are the leading cause of
      bacterial resistance to these drugs. Although beta-lactamases have been
      extensively studied, structures of the substrate-enzyme and product-enzyme
      complexes have proven elusive. Here, the structure of a mutant AmpC in complex
      with the beta-lactam cephalothin in its substrate and product forms was
      determined by X-ray crystallography to 1.53 A resolution. The acyl-enzyme
      intermediate between AmpC and cephalothin was determined to 2.06 A resolution.
      The ligand undergoes a dramatic conformational change as the reaction progresses,
      with the characteristic six-membered dihydrothiazine ring of cephalothin rotating
      by 109 degrees. These structures correspond to all three intermediates along the
      reaction path and provide insight into substrate recognition, catalysis, and
      product expulsion.

PMID- 12005440
TI  - The 1.9 A structure of alpha-N-acetylgalactosaminidase: molecular basis of
      glycosidase deficiency diseases.
AB  - In the lysosome, glycosidases degrade glycolipids, glycoproteins, and
      oligosaccharides. Mutations in glycosidases cause disorders characterized by the
      deposition of undegraded carbohydrates. Schindler and Fabry diseases are caused
      by the incomplete degradation of carbohydrates with terminal alpha-N
      acetylgalactosamine and alpha-galactose, respectively. Here we present the X-ray
      structure of alpha-N-acetylgalactosaminidase (alpha-NAGAL), the glycosidase that
      removes alpha-N-acetylgalactosamine, and the structure with bound ligand. The
      active site residues of alpha-NAGAL are conserved in the closely related enzyme a
      galactosidase A (alpha-GAL). The structure demonstrates the catalytic mechanisms
      of both enzymes and reveals the structural basis of mutations causing Schindler
      and Fabry diseases. As alpha-NAGAL and alpha-GAL produce type O "universal donor"
      blood from type A and type B blood, the alpha-NAGAL structure will aid in the
      engineering of improved enzymes for blood conversion.

PMID- 12005441
TI  - Reliability of assessment of protein structure prediction methods.
AB  - The reliability of ranking of protein structure modeling methods is assessed. The
      assessment is based on the parametric Student's t test and the nonparametric
      Wilcox signed rank test of statistical significance of the difference between
      paired samples. The approach is applied to the ranking of the comparative
      modeling methods tested at the fourth meeting on Critical Assessment of
      Techniques for Protein Structure Prediction (CASP). It is shown that the 14 CASP4
      test sequences may not be sufficient to reliably distinguish between the top
      eight methods, given the model quality differences and their standard deviations.
      We suggest that CASP needs to be supplemented by an assessment of protein
      structure prediction methods that is automated, continuous in time, based on
      several criteria applied to a large number of models, and with quantitative
      statistical reliability assigned to each characterization.

PMID- 12005442
TI  - Comparative studies of the Acinetobacter genus and the species identification
      method based on the recA sequences.
AB  - The recA gene is indispensable for a maintaining and diversification of the
      bacterial genetic material. Given its important role in ensuring cell viability,
      it is not surprising that the RecA protein is both ubiquitous and well conserved
      among a range of prokaryotes. Previously, we reported Acinetobacter genomic
      species identification method based on PCR amplification of an internal fragment
      of the recA gene with subsequent restriction analysis (RFLP) with HinfI and MboI
      enzymes. In present study, the PCR products containing the internal fragment of
      the recA gene, for 25 Acinetobacter strains belonging to all genomic species,
      were sequenced. Based on the nucleotide sequences the restriction maps and
      phylogenetic tree were prepared. The restriction maps revealed that Tsp509I
      restriction enzyme is the most discriminating for RFLP. To verify the computer
      analysis, the amplified DNAs from all reference genomic species available (43
      strains) and 34 clinical strains were digested with each of the three restriction
      endonucleases mentioned. The results of digestion confirmed the computer
      analysis. The reconstructed phylogenetic tree showed linkages between genomic
      species 1 (Acinetobacter calcoaceticus), 2 (Acinetobacter baumannii), 3, 'between
      1 and 3', TU13 and 'close to TU13'; genomic species 4, 6, BJ13, BJ14, BJ15, BJ16
      and BJ17; genomic species 7 (Acinetobacter johnsonii) and TU14; genomic species
      10 and 11; genomic species 8 (Acinetobacter Iwoffii), 9, 12 (Acinetobacter
      radioresistens) and TU15; and genomic species 5 (Acinetobacter junii). It is
      interesting that one branch in the phylogenetic tree contains haemolytic species
      genomic species 4 (A. haemolyticus), BJ13, BJ14, BJ15, BJ16 and BJ17. The
      proposed genotypic method clearly revealed that the RFLP profiles obtained with
      Tsp509I enzyme might be useful for species identification of Acinetobacter
      strains. In this context, recA/RFLP genotypic method should be seen as an ideal
      preliminary screening method for large numbers of isolates, with the ultimate
      confirmatory role reserved for DNA hybridization analysis.

PMID- 12005443
TI  - Quantification of PCR amplification products of Brugia HhaI repeat DNA using a
      semiautomated Q-PCR system.
AB  - The sensitive, rapid and species-specific diagnosis of Brugia infections in
      humans or animal models is important in determining the level of parasitemia and
      the efficacy of chemotherapy or vaccinations. The HhaI family of highly repeated
      DNA sequences from Brugia have been useful in polymerase chain reaction (PCR)
      based diagnosis of brugian filarial infections in blood samples and in
      mosquitoes. A PCR assay was developed using a biotinylated primer, a non
      biotinylated primer and a species-specific chemiluminescent probe
      [tris[2,2'bipyridine] ruthenium (II) chelate, TBR] to detect PCR amplified Hhal
      family repeats. Individual blood samples from jirds infected with Brugia malayi
      or B. pahangi and with different levels of microfilaremia were tested in this
      assay. Known concentrations of Brugia DNA and DNA from the blood of uninfected
      control jirds were used as positive and negative controls, respectively. The PCR
      products generated by this method were analyzed using a semi-automated
      quantitative (Q)-PCR system. The levels of parasite DNA can be calculated from
      the luminosity units generated. Significant amounts of parasite DNA were detected
      in blood samples from infected jirds, and these values were correlated with the
      levels of microfilaremia. In contrast, reductions in circulating microfilaria
      following treatment with ivermectin correlated with low levels of measurable DNA.
      Using this system, we were also able to detect HhaI repeat DNA in the spleens of
      B. pahangi- infected jirds at 56 days post-infection when circulating
      microfilariae were not readily detectable. The results indicate that the species
      specific Hhal Q-PCR detection and quantification method is rapid and sensitive,
      is useful in the detection of Brugia DNA in blood and other tissues and is suited
      for use in clinical settings because it does not require radioactive isotopes and
      gel-based protocols.

PMID- 12005444
TI  - Quantitative analysis of beta-actin, beta-2-microglobulin and porphobilinogen
      deaminase mRNA and their comparison as control transcripts for RT-PCR.
AB  - Quantitation of target mRNAs using the reverse-transcription polymerase chain
      reaction found a widespread field of application in diverse biomedical diagnostic
      assays. However, the problem of varying sample quality has to be solved by
      correcting target molecule amounts through detection of an endogenous control
      template. The choice of an appropriate reference gene is still object of debate
      as pseudogene co-amplification and expression level variations may limit the
      usefulness of some currently used reference reactions. We compared quantitative
      expression levels of the commonly used endogenous reference genes beta-actin
      (beta-actin), beta-2-microglobulin (beta2-MG) and porphobilinogen deaminase
      (PBDG) using the TaqMan chemistry. With these assays we investigated the
      respective expression patterns in K562 cells and leucocytes of normal individuals
      as well as of malignoma patients. In K562 cells 1544+246 beta-actin, 65+30 beta2
      MG and 22+/-8 PBDG copies/cell were detected. In normal leucocytes 491+/-97 beta
      actin, 40+/-17 beta2-MG and <1 PBDG copies/cell were quantified. Leucocytes of
      various malignancies exhibited 84+/-51 beta-actin, 106+/-8 beta2-MG and <1 PBDG
      copies/cell. We conclude that beta2-MG is the most suitable reference gene tested
      as its variation between different sample origins and within distinct cell types
      was acceptable low.

PMID- 12005445
TI  - Efficacy of a novel reverse transcriptase-polymerase chain reaction (RT-PCR) for
      detecting Toxoplasma gondii bradyzoite gene expression in human clinical
      specimens.
AB  - A reverse transcriptase-polymerase chain reaction (RT-PCR) assay, was performed
      to evaluate the transcription degree of bradyzoite- or tachyzoite-specific genes
      of Toxoplasma gondii on cerebrospinal fluid (CSF) specimens from AIDS patients
      with toxoplasmic encephalitis (TE), and to distinguish an asymptomatic latent
      infection from a reactivated disease. This method was compared with nested DNA
      amplification (n)-PCR. The mRNA expression of the representative T. gondii cystic
      matrix (MAG1) or bradyzoite-specific (SAG4) genes was investigated on CSF
      obtained from AIDS patients with first episode (no. 11) or relapse (no. 8) of TE.
      The mRNA expression of tachyzoite-specific (SAG1) gene was also studied. New
      designed oligonucleotide primers and probes, which identify a 212 bp fragment
      inside to the open reading MAG1 sequence, were employed in both RT-PCR and n-PCR
      assays. Oligo-dT primed cDNA synthesis appeared a suitable method for subsequent
      analysis by n-PCR. RT-PCR has been shown to be more sensitive and specific than n
      PCR. MAG1 and SAG4 gene expression was detected in 8 (100%) and 6 (75%) patients
      with TE relapses, respectively, while SAG1 detected 7 (63%) patients with TE
      first episode. These findings suggest that RT-PCR method is able to identify the
      bradyzoite stage of T. gondii especially in patients who are at risk for TE
      relapse.

PMID- 12005446
TI  - In situ identification of mycobacteria in Crohn's disease patient tissue using
      confocal scanning laser microscopy.
AB  - The diversity in the methodology employed to investigate Crohn's disease (CD)
      etiology has added significantly to the controversy of the mycobacterial role in
      this chronic inflammatory bowel disease. Mycobacterium avium subsp
      paratuberculosis (MAP), a proposed and suspected agent in many CD patients, is a
      fastidious and very slow grower bacillus, which causes Johne's disease (JD) in
      cattle. The methodology that has been widely and successfully used for isolation
      and identification of MAP from and in JD animals is not reliable and has proven
      to be unsuccessful in achieving the same objectives for CD diagnosis. In this
      study, a Confocal Scanning Laser Microscopy (CSLM) system has been employed in an
      attempt to detect MAP in CD patient. In situ hybridization was performed on full
      thickness tissue using rabbit anti-MAP polyclonal antibody that was adsorbed with
      E. coli protein extracts. Consequently, MAP was detected in the microvilli region
      in tissue specimens from CD patient and not in the controls. In the same CD
      tissue specimen, MAP was not detected when isotype normal rabbit sera was
      employed. The polyclonal antibody marker may be replaced with monoclonal
      antibodies, if available, or with MAP-specific-DNA or RNA probes. This technique
      adds an additional approach to investigate MAP role in CD etiology especially
      when the culture approach is long and inconsistent.

PMID- 12005447
TI  - In situ detection of Bartonella henselae cells.
AB  - A new in situ hybridization technique was developed for identification of
      Bartonella henselae cells in cell suspension or in tissue sections. Use of highly
      specific probes labeled with either fluorescein or digoxigenin allows
      discrimination between B. henselae and closely related B. quintana cells. No
      cross-hybridization with other Bartonella or non-Bartonella species was observed.
      Besides its specificity it showed higher sensitivity as compared to PCR based
      detection methods. Moreover, its application allows direct observation of B.
      henselae in infected tissues.

PMID- 12005448
TI  - Novel PCR-EIA method for the detection of Chlamydia pneumoniae in respiratory
      specimens.
AB  - We report the development of a microtitre plate-based PCR-EIA assay (ELAHA;
      Enzyme Linked Amplification and Hybridization Assay) for the sensitive and
      specific detection of Chlamydia pneumoniae in sputum samples from patients with
      chronic obstructive airways disease (COAD). Following PCR amplification of a
      segment of the chlamydial heat shock 60 protein gene, the 587 bp sized amplicon
      is captured onto the streptavidin coated surface of a microtitre plate using a C.
      pneumoniae specific biotinylated probe and the level of captured product is
      subsequently determined via a colorimetric reaction using an automated plate
      reader. The ELAHA is a simple, rapid and inexpensive method for detection of low
      levels of infectious agents and is readily adaptable to current clinical
      laboratory equipment. The assay was evaluated with a cohort of hospital
      respiratory patients: (i) COAD patients with acute exacerbation, (ii) COAD
      patients without exacerbation (stable) and (iii) a non-respiratory control group.
      The ELAHA produced 6/12 (50%) C. pneumoniae positives in the COAD with
      exacerbation group, 3/13 (23%) positives in the COAD without exacerbation group
      and only 1/6 (17%) positives in the control non-respiratory group. This sensitive
      and robust PCR-EIA method can provide clinically relevant diagnostic evidence of
      current C. pneumoniae infection contributing to serious respiratory tract
      diseases such as COAD.

PMID- 12005449
TI  - A newly identified single nucleotide polymorphism in the promoter of the matrix
      metalloproteinase-1 gene.
AB  - Matrix metalloproteinase-1 (MMP-1) is a member of the matrix metalloproteinase
      enzyme family that degrades components of the extracellular matrix. Recent
      studies have demonstrated several polymorphic sites in the promoter of the MMP-1
      gene. A newly identified single nucleotide polymorphism (SNP) at position -519 in
      the promoter region of the MMP-1 gene is reported. This polymorphism consists in
      a guanine to adenine substitution. A linkage between polymorphisms -519A/G and 
      1607 1G/2G was also studied.

PMID- 12005450
TI  - FISSR-PCR: a simple and sensitive assay for highthroughput genotyping and genetic
      mapping.
AB  - The recently developed Inter-Simple Sequence Repeat PCR (ISSR-PCR) or
      microsatellite primed PCR or Simple Sequence Repeat (SSR)-Anchored PCR technique
      detects polymorphic markers in a wide variety of genomes. Usually the ISSR
      primers are either 5' end-labeled with gamma[32P]ATP or one of the alpha[32P]
      labeled dNTPs is added to the PCR reaction and the PCR products are resolved on
      PAGE and autoradiographed. Alternatively, cold PCR products are resolved on
      agarose gel electrophoresis. In the present study, we show that informativity,
      sensitivity and speed of the ISSR-PCR can be substantially enhanced by adding
      fluorescent nucleotide in the PCR reaction followed by resolution of PCR products
      on an ABI 377 automated sequencer. The informativeness, measured as a number of
      detectable amplified fragments, was two-fold higher and the quantity of required
      template DNA is two-fold lower than the regular ISSR-PCR. We have termed this
      method as FISSR-PCR and show its usefulness in generating large number of species
      and varietal specific markers in plants, insects, parasites of insects and human
      and various infectious organisms. Further, we show that the FISSR markers are
      inherited and segregated in Mendelian fashion as demonstrated on a panel of 99 F2
      offspring derived from a cross of two divergent silkworm strains. The FISSR-PCR
      marker assay could be a method of choice for large scale screening of
      varieties/cultivars and highthroughput genotyping in mapping of genomes where
      microsatellite information is scanty or absent.

PMID- 12005451
TI  - Rapid and efficient genotype analysis of the COL1a1 Sp1 binding site dimorphism,
      a genetic marker for bone mineral density.
AB  - A biallelic G/T polymorphism within the first intron of COL1A1 gene at a
      recognition site for the transcription factor Sp1 has been shown to be
      significantly related to bone mass and osteoporotic fracture. To date this
      polymorphism has been detected by conventional genomic DNA amplification followed
      by restriction enzyme digestion and polyacrylamide gel electrophoresis. We have
      designed a rapid and efficient genotyping method based on allele-specific
      polymerase chain reaction

PMID- 12005452
TI  - Detection and genetic characterization of canine distemper virus (CDV) from free
      ranging red foxes in Italy.
AB  - Fragments of the genes encoding the haemoagglutinin (H) and the nucleocapsid
      protein (N) of a canine distemper (CDV)-like virus affecting a red fox (Vulpes
      vulpes) were sequenced and analysed. The CDV-like virus detected in the fox was
      found to be not dissimilar, in both the H and N gene, from other CDVs spreading
      in Italy, as well as all over the world, and phylogenetic analysis on the H
      protein-encoding gene allowed to include all the Italian CDVs in the H European
      genotype.

PMID- 12005453
TI  - Short-chain fatty acids and total parenteral nutrition affect intestinal gene
      expression.
AB  - BACKGROUND: The supplementation of total parenteral nutrition (TPN) formulas with
      short-chain fatty acids (SCFAs) increases glucose uptake and the expression of
      glucose transporters in parenterally fed animals. Several signals may be involved
      in intestinal adaptation; however, increased messenger RNA (mRNA) levels for
      proglucagon and several early-response genes, including c-myc and c-fos, are seen
      in animals receiving SCFA-supplemented TPN. Although the effects of a mixture of
      SCFAs are well documented, the relative contribution of individual SCFAs is
      unknown. Butyrate is a preferred fuel of colonocytes, with documented effects on
      cellular proliferation and gene expression. Accordingly, this study was
      undertaken to determine the relative role of butyrate in initiating an adaptive
      response in nonresected rats receiving TPN. METHODS: Animals received standard
      TPN for 66 hours, followed by 6 hours of either standard TPN, TPN supplemented
      with a mixture of SCFAs (acetate, propionate, and butyrate, 60 mmol/L total), or
      TPN supplemented with butyrate alone (9 mmol/L). An oral control group was fed an
      elemental diet, similar in macronutrient content to the TPN, so that all animals
      received the same amount of energy daily. RESULTS: SCFAs increased ileal glucose
      transporter 2 (GLUT2) mRNA expression compared with the orally fed group. SCFAs
      also increased proglucagon mRNA expression compared with the TPN group. No
      changes in Na+K(+)-adenosine triphosphatase or early-response gene expression
      were found in this study. CONCLUSIONS: In a rat model of TPN, the use of 9 mmol/L
      butyrate did not have the same effect on GLUT2 and proglucagon expression as a 60
      mmol/L mixture of SCFAs. This suggests that the effect of a mixture of SCFAs on
      intestinal gene expression is not butyrate specific.

PMID- 12005454
TI  - A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid
      based lipid infusion in atopic dermatitis.
AB  - BACKGROUND: In the involved epidermis of patients with atopic dermatitis, changes
      in the metabolism of eicosanoids with increased quantities of the arachidonic
      acid (AA)-derived lipoxygenase products have been observed. Free eicosapentaenoic
      acid (EPA), a fish oil-derived alternative (n-3) fatty acid, may compete with AA,
      resulting in an anti-inflammatory effect. METHODS: In a 10-day double-blind,
      randomized, placebo-controlled trial, 22 patients hospitalized for moderate-to
      severe atopic dermatitis were randomly assigned to receive daily infusions of
      either a n-3 fatty acid-based lipid emulsion (fish oil, 10%; 200 mL/d) or a
      conventional n-6-lipid emulsion (soybean oil, 10%; 200 mL/d). Topical treatment
      was restricted to emollients. The severity of disease was evaluated daily with
      scoring of erythema, infiltration, and desquamation and by subjective patient
      scoring of clinical manifestations. In addition, plasma-free and total-bound
      fatty acids and the composition of membrane fatty acids in blood cells
      (thrombocytes, granulocytes, and erythrocytes), lipid mediators from isolated
      neutrophils and platelets, and lymphocyte-activation parameters were determined.
      RESULTS: Twenty patients completed the trial. Marked improvement from baseline
      was seen in both groups. On days 6, 7, 8, and 10, disease severity score-defined
      as the sum of all scores-was more pronounced (p < .05) in the n-3 group compared
      with the n-6 group. Free arachidonic acid in plasma did not change substantially
      in both groups, whereas plasma-free EPA, total-bound EPA, and the membrane EPA/AA
      ratio markedly increased in response to n-3-lipid infusion. In parallel, EPA
      derived lipid mediators appeared, whereas lymphocyte functions were unaffected.
      In the post-treatment period (2/4 weeks), relapse was observed in some patients
      after n-3 psoralene-ultraviolet A (PUVA) infusion, whereas there was a marked
      long-term improvement in the n-6 group. CONCLUSIONS: IV n-3-fatty acid
      administration is effective in acutely improving the severity of atopic
      dermatitis, paralleled by changes in plasma and membrane fatty acid composition
      and lipid mediator synthesis. The long-term beneficial effects of IV n-6 fatty
      acids should be evaluated further.

PMID- 12005455
TI  - Home parenteral nutrition: does affiliation with a national support and
      educational organization improve patient outcomes?
AB  - BACKGROUND: For patients receiving home parenteral nutrition (HPN), catheter
      related bloodstream infection (CRBSI) and reactive depression may significantly
      impact quality-of-life. This study evaluated the influence of patient affiliation
      with a national organization promoting HPN education and peer support on these
      outcome variables. METHODS: Using a case-control design, we compared 2 groups of
      affiliated patients with nonaffiliated controls, who were matched for diagnosis,
      HPN duration, sex, and age. Group 1 data were obtained from patients in large HPN
      medical practice programs. Group 2 data were obtained from patients in small
      medical practices with a small number of HPN patients. All participants were
      evaluated by structured interviews every 6 months over 18 months. RESULTS: In
      both data collection groups, affiliated patients (A) had significantly higher
      (mean +/- SD) quality-of-life scores compared with nonaffiliated patients (NA):
      (Gr 1: A, 19.8 +/- 4.7 versus NA, 17.6 +/- 5.6, p = .05; Gr 2: A, 20.4 +/- 5.2
      versus NA, 17.3 +/- 4.8, p = .05). Affiliated patients also had lower depression
      scores (Gr 1: A, 10.9 +/- 10.4 versus NA, 20.4 +/- 13.6, p = .01; Gr 2: A, 12.5
      +/- 9.6 versus NA, 18.5 +/- 10.8, p = .03) and a lower incidence of catheter
      related infections (Gr 1: A, 0.10 +/- 0.3 versus NA, 0.60 +/- 0.55, p = .01; Gr
      2: A, 0.27 +/- 0.55 versus NA, 0.71 +/- 0.64, p = .02) than nonaffiliated
      patients. CONCLUSIONS: Affiliation with an organization that provides ongoing HPN
      education and peer support was associated with significantly better HPN outcomes.
      Alternative explanations are discussed in relation to limitations of the case
      control design.

PMID- 12005456
TI  - Longitudinal assessment of outcome, health status, and changes in lifestyle
      associated with long-term home parenteral and enteral nutrition.
AB  - BACKGROUND: The purpose of this study was to assess the health status, frequency
      of therapy-related symptoms, and impact of home parenteral and enteral nutrition
      (HPEN) on lifestyle in patients who were stable and had nonmalignant diagnoses.
      Assessments were made at 2 time points, 3 years apart. METHODS: Institutional
      review board approval was obtained. Adult HPEN patients self-completed a general
      health status questionnaire (SF-36) and a lifestyle-symptom questionnaire in 1993
      and 1996. Demographic data relating to underlying disease state and infusion
      regimen were also collected. RESULTS: Seventeen patients (7 men, 10 women; 13
      receiving home parenteral nutrition [HPN] and 4 receiving home enteral nutrition
      [HEN]) participated in the study. The mean (SEM) duration of HPEN therapy at the
      start of the study was 7.1 (1.6) years. Although health status as assessed by SF
      36 scores was lower in all categories when compared with age- and gender-matched
      control data from the general US population (p < .05), there was no significant
      difference in SF-36 scores between the 2 time periods (p > .05). Sleep, travel,
      and social activities were the most affected aspects of the patient's lifestyle.
      CONCLUSIONS: These data suggest that patients with nonmalignant underlying
      disease receiving HPEN maintain a stable health status over a prolonged period.

PMID- 12005457
TI  - Total parenteral nutrition supplementation with glutamine improves survival after
      gut ischemia/reperfusion.
AB  - BACKGROUND: Total parenteral nutrition (TPN) alters gut cytokines and mucosal
      immunity and increases intercellular adhesion molecule-1 (ICAM-1) expression, gut
      neutrophil levels, and mortality after gut ischemia. Supplementation of TPN with
      glutamine partially supports mucosal immunity by preserving respiratory and
      intestinal IgA levels, maintaining the proper IgA-stimulating cytokine milieu
      within the intestine, and reducing intestinal ICAM-1 expression and neutrophil
      accumulation. This work investigates whether glutamine supplementation of TPN
      affects mortality in mice after gut ischemic insult. METHODS: Thirty-eight mice
      were randomized to receive chow, TPN, or 2% glutamine-supplemented TPN (GLN-TPN)
      for 5 days. After feeding their respective diets, gut ischemia/reperfusion (I/R)
      was induced with superior mesenteric artery occlusion for 30 minutes followed by
      resuscitation with 1 mL saline. Survival was recorded until 72 hours after
      reperfusion. RESULTS: Survival time was significantly reduced in the TPN-fed mice
      compared with both chow-fed and GLN-TPN-fed mice (p < .05). Survival at 72 hours
      after reperfusion was also significantly lower in the TPN-fed mice than in the
      chow-fed and GLN-TPN-fed mice (p < .05) CONCLUSIONS: Glutamine supplementation of
      TPN significantly improves survival after gut I/R, suggesting modulation of the
      inflammatory response or improved gut tolerance to low-flow states.

PMID- 12005458
TI  - Early versus late enteral feeding of mechanically ventilated patients: results of
      a clinical trial.
AB  - BACKGROUND: This study sought to compare 2 strategies for the administration of
      enteral feeding to mechanically ventilated medical patients. METHODS: The
      prospective, controlled, clinical trial was carried out in a medical intensive
      care unit (19 beds) in a university-affiliated, urban teaching hospital. Between
      May 1999 and December 2000, 150 patients were enrolled. Patients were scheduled
      to receive their estimated total daily enteral nutritional requirements on either
      day 1 (early-feeding group) or day 5 (late-feeding group) of mechanical
      ventilation. Patients in the late-feeding group were also scheduled to receive
      20% of their estimated daily enteral nutritional requirements during the first 4
      days of mechanical ventilation. RESULTS: Seventy-five (50%) consecutive eligible
      patients were entered into the early-feeding group and 75 (50%) patients were
      enrolled in the late-feeding group. During the 5 five days of mechanical
      ventilation, the total intake of calories (2370 +/- 2000 kcal versus 629 +/- 575
      kcal; p < .001) and protein (93.6 +/- 77.2 g versus 26.7 +/- 26.6 g; p < .001)
      were statistically greater for patients in the early-feeding group. Patients in
      the early-feeding group had statistically greater incidences of ventilator
      associated pneumonia (49.3% versus 30.7%; p = .020) and diarrhea associated with
      Clostridium difficile infection (13.3% versus 4.0%; p = .042). The early-feeding
      group also had statistically longer intensive care unit (13.6 +/- 14.2 days
      versus 9.8 +/- 7.4 days; p = .043) and hospital lengths of stay (22.9 +/- 19.7
      days versus 16.7 +/- 12.5 days; p = .023) compared with patients in the late
      feeding group. No statistical difference in hospital mortality was observed
      between patients in the early-feeding and late-feeding groups (20.0% versus
      26.7%; p = .334). CONCLUSIONS: The administration of more aggressive early
      enteral nutrition to mechanically ventilated medical patients is associated with
      greater infectious complications and prolonged lengths of stay in the hospital.
      Clinicians must balance the potential for complications resulting from early
      enteral feeding with the expected benefits of such therapy.

PMID- 12005459
TI  - The calorie conundrum.

PMID- 12005460
TI  - Nutritional assessment of serum and hepatic vitamin A levels in patients with
      cirrhosis.
AB  - BACKGROUND: Serum vitamin A (retinol) levels may not correlate with hepatic
      vitamin A stores in patients with cirrhosis; thus, supplementation of vitamin A
      based on serum levels may have a detrimental effect. Our aim was to determine
      whether serum levels correlate with hepatic stores in cirrhotic patients.
      METHODS: A prospective study of patients with cirrhosis undergoing orthotopic
      liver transplantation was completed. Serum and hepatic levels of vitamin A were
      measured by high-performance liquid chromatography. Statistical analysis was
      performed using rank sum tests and Spearman rank correlation coefficients.
      RESULTS: Fifty cirrhotic patients (33 men and 17 women, mean age 53 years) were
      compared with a control group (25 men and 25 women, mean age 47 years) of liver
      donors. Median serum levels of retinol were 259 microg/L in controls and 166
      microg/L in cirrhotic patients (p < .001). Median hepatic levels of retinol were
      25 microg/g in controls and 27.5 +/- g/g in cirrhotic patients (p not
      significant). Total hepatic vitamin A levels (retinol plus retinyl esters) were
      471 microg/g in controls and 244 microg/g in cirrhotic patients (p = .028). Serum
      retinol did not correlate with total hepatic vitamin A stores in cirrhotic
      patients (rs = .10, p = .332). CONCLUSIONS: Serum retinol and total hepatic
      vitamin A stores are lower in cirrhotic patients than in controls. However,
      because levels of serum retinol do not correlate with hepatic vitamin A levels,
      the decision to prescribe vitamin A replacement for patients with cirrhosis
      should not be made solely on the basis of serum retinol levels.

PMID- 12005461
TI  - A longitudinal evaluation of oxidative stress in trauma patients.
AB  - BACKGROUND: The purpose of this study was to determine the course of oxidative
      stress in trauma patients as measured by antioxidant disappearance and modulation
      of DNA damage. The study also explored the role of injury severity and the effect
      of changes in plasma lipoprotein concentration as the result of hemodilution on
      lipid-soluble plasma antioxidant concentrations. METHODS: The study population
      included 17 adult male trauma patients in an urban level-1 trauma hospital and 12
      healthy adult male controls. Blood was collected immediately after admission in
      the emergency room, and on days 2, 3, 4, 6, and 8 of admission. Plasma
      antioxidant concentrations and total cholesterol concentrations were evaluated.
      DNA damage was evaluated using the ratio of 8-hydroxydeoxyguanosine to
      deoxyguanosine (8OhdG to dG). Admission data were compared with data from
      controls. RESULTS: Plasma antioxidant concentrations (except alpha-tocopherol)
      significantly decreased by 9.9% to 34.3% in the 24 hours after trauma and
      remained depressed throughout day 8. Repeated measures regression analysis for
      trend showed a significant increase in unadjusted alpha-tocopherol from day 1 to
      day 8 (p < .008). No other unadjusted antioxidant or plasma cholesterol showed a
      significant change. After individually adjusting antioxidant concentrations by
      total cholesterol, only gamma-tocopherol (22.2%) and lycopene (22.6%) were
      decreased (p < .04) in the 24 hours after trauma. Repeated measures regression
      analysis for trend for the cholesterol-adjusted antioxidants showed a significant
      decrease from day 1 to day 8 for cholesterol-adjusted alpha-carotene (p < .007)
      and beta-carotene (p < .007). Trauma patients were divided into more and less
      severely injured groups based on Injury Severity Score (ISS). Decreases in
      antioxidant concentration from day 1 to day 2 were found for the patients in the
      more injured group, with no significant differences from day 1 to day 2 in the
      less severely injured group. Cholesterol-adjusted gamma-to copherol (29.7%, p <
      .003) and lycopene (32.7%, p < .05) decreased from day 1 to day 2 in the more
      severely injured group. Using repeated measures regression analysis for trend,
      the only antioxidant that was significantly different in the high versus low ISS
      groups from day 1 through day 6 was cholesterol-adjusted lutein-zeaxanthin (p <
      .02). Compared with controls, trauma patients had significantly lower (27.3% to
      64.9%) concentrations of all cholesterol-adjusted antioxidants at day 1 except
      for lycopene. Trauma patients had higher leukocyte 8OhdG to dG ratios at
      admission (42.6%, p < .05), but 8OhdG to dG ratios tended to decrease over the 24
      hours after trauma (p < .07). This decrease was greater in the 3 trauma patients
      with an admission 8OhdG to dG ratio greater than 6 x 10(-5) (59.3% versus 0.05%,
      p < .03). CONCLUSIONS: The difference in antioxidant concentrations between
      trauma patients and controls may have been associated with oxidative stress or
      with a poorer diet. The difference between antioxidant concentrations and
      cholesterol-adjusted antioxidant concentrations is likely caused by hemodilution
      or by changes in plasma lipid levels as a result of trauma. Therefore,
      individually adjusting lipid-soluble antioxidant concentrations by total
      cholesterol concentrations is important in trauma patients. Leukocyte 8OhdG to dG
      ratios were already elevated in trauma patients on admission but returned nearly
      to control levels 24 hours later, indicating short-term responsiveness to DNA
      oxidation in trauma patients and an extensive capacity for DNA repair within 24
      hours.

PMID- 12005462
TI  - Motility of the gastrointestinal tract and gallbladder during long-term total
      parenteral nutrition in dogs.
AB  - BACKGROUND: The motility of the gastrointestinal tract during total parenteral
      nutrition (TPN) remains poorly understood. The objective of this study was to
      determine the motility pattern not only in the gastrointestinal tract but also in
      the gallbladders of dogs maintained by TPN. METHODS: Central venous catheters
      were inserted through the external jugular vein of 5 dogs and 6 strain gauge
      force transducers were sewn to the stomach, small intestine, and gallbladder. Two
      weeks later, oral food was discontinued and motility was recorded for 24 hours
      after the first migrating motor complex (MMC) was confirmed in the stomach as pre
      TPN. TPN was started and continued for 4 weeks, and patterns of motor activity
      during TPN were recorded for 24 hours at the end of each week. RESULTS: The
      durations of MMC in the stomach, duodenum, and gallbladder in pre-TPN were 118 +/
      3 minutes, 118 +/- 2 minutes, and 118 +/- 2 minutes, respectively, but in the
      first week of TPN they were 432 +/- 56 minutes, 431 +/- 56 minutes, and 386 +/-
      29 minutes, respectively. TPN times were significantly longer than those of pre
      TPN (corrected p < .005). The durations of MMC in jejunoileum did not alter
      between pre-TPN and TPN. The occurrences of phase III in the stomach, duodenum,
      and gallbladder in pre-TPN were 12/d, but during TPN they were reduced
      significantly (corrected p < .005). CONCLUSIONS: TPN did not affect the motility
      of the jejunoileum but did inhibit the motor activities of the stomach, duodenum,
      and gallbladder. The inhibition of gallbladder contraction observed during TPN
      may be one of the factors inducing gallbladder disease.

PMID- 12005463
TI  - A comparison of the effect of elemental and immune-enhancing polymeric jejunal
      feeding on exocrine pancreatic function.
AB  - BACKGROUND: There are few studies examining the effect of jejunal feeding on
      pancreatic exocrine output. The purpose of this study was to compare the effects
      of jejunal feeding with an elemental formula (EF) and with a polymeric immune
      enhancing formula (PIEF) on pancreatic exocrine function. METHODS: Patients
      undergoing a partial pancreatectomy had a jejunal feeding tube inserted and a
      pancreatic stent exteriorized, facilitating collection of pancreatic secretions.
      Postoperatively, patients underwent a secretin-stimulation test to document
      adequate pancreatic reserve. Patients were then randomized to receive jejunal
      feeding with EF or with PIEF for a 24-hour period, followed by a washout period
      of feeding with dextrose, and subsequent jejunal feeding with EF or PIEF.
      RESULTS: The secretin-stimulation test demonstrated significant pancreatic
      reserve in all patients. There was a mild increase in pancreatic exocrine
      secretion with jejunal feeding with EF and PIEF compared with baseline and with
      dextrose. There was increased bicarbonate secretion with EF compared with PIEF,
      but there were no other significant differences in pancreatic exocrine function.
      CONCLUSIONS: In this model of partial pancreatectomy, there was no significant
      difference in pancreatic exocrine output when use of an EF was compared with use
      of a PIEF for jejunal feeding. Further clinical studies are needed to determine
      the potential role of PIEF in pancreatic disease.

PMID- 12005464
TI  - Continuation of transpyloric feeding during weaning of mechanical ventilation and
      tracheal extubation in children: a randomized controlled trial.
AB  - BACKGROUND: Nutrition support is essential in the management of critically ill
      children. There is no current literature to support the common practice of
      discontinuing enteral nutrition delivered through a transpyloric feeding tube
      during the tracheal extubation process. We conducted a prospective, randomized
      controlled trial in mechanically ventilated children to examine the safety and
      efficacy of continuous transpyloric feeding compared with interrupted
      transpyloric feeding at the time of tracheal extubation. METHODS: Subjects were
      randomly assigned to receive transpyloric feeding throughout the tracheal
      extubation process (Continuous Group) or to have transpyloric feeding
      discontinued 4 hours before tracheal extubation and restarted 4 hours after
      tracheal extubation (Interrupted Group). Data consisting of patient demographics,
      admission pediatric risk of mortality (PRISM) score, diagnoses, adverse events
      (feeding intolerance, gastroesophageal reflux, and pulmonary aspiration), daily
      feeding volume, and caloric intake were recorded for the 3 days surrounding
      tracheal extubation. RESULTS: Fifty-nine patients completed the study (29 in
      Continuous Group, 30 in Interrupted Group). There was no episode of pulmonary
      aspiration in either group. The Continuous Group experienced 4 adverse events,
      whereas the Interrupted Group experienced 3 adverse events (p = not significant).
      The Continuous Group received 92 +/- 2.5% of their caloric goal on the day of
      weaning from the ventilator (day 1) and 93 +/- 3.2% on the day of tracheal
      extubation (day 2) compared with 76 +/- 4.2% and 43 +/- 4.3%, respectively, in
      the Interrupted Group (p < .004 and p < .0001, respectively). CONCLUSIONS:
      Continuous transpyloric feeding during weaning from the ventilator and tracheal
      extubation is safe and results in the delivery of more optimal nutrition.

PMID- 12005465
TI  - Sleep patterns of cyclic parenteral nutrition, a pilot study: are there sleepless
      nights?
AB  - BACKGROUND: Cyclic home parenteral nutrition (HPN) is 1 of the few medical
      therapies given during normal nocturnal sleep hours, and it is possible that
      infusion may alter normal sleep patterns. The aim of this pilot study was to
      evaluate the sleep patterns of 5 patients receiving HPN. METHODS: An Epworth
      sleep questionnaire was completed and wrist Actigraph data were collected before
      admission to the sleep laboratory. Formal overnight polysomnography was then
      preformed for 3 consecutive nights. The first night served as the acclimatization
      period. On the second and third nights, patients were randomized to receive
      either no infusion or infusion of their standard parenteral nutrition. Results
      were reported as the median and range and were compared with historical aged
      matched controls. RESULTS: Five patients (3 women and 2 men) with a mean age of
      61 years (40 to 73 years) were studied. Patients had been HPN-dependent for a
      median of 23 months (4 to 60 months). Patients were receiving HPN because of
      short bowel syndrome (2), chronic pancreatitis (2), and intestinal
      pseudoobstruction (1). A 1.5-liter HPN formula, infused over 10 hours, included
      approximately 25 kcal/kg/d with 30% lipid and 1.0 to 1.5 g/kg/d of protein. All
      solutions included multiple trace elements and standard multivitamins. During
      total parenteral nutrition (TPN) infusion, the percent of sleep efficiency was
      higher than without infusion, 81% versus 72%. Sleep efficiency in age-matched
      controls was approximately 88%. Sleep latency was longer in patients compared
      with controls, and longer in patients during infusion than without infusion, 35
      versus 28 minutes. During TPN infusion, the percent of stage-1 (2%), stage-2
      (52%), slow-wave (24%) and random eye movement (REM) sleep (21%) was similar to
      values during the night without infusion. Controls had lower slow-wave and REM
      times. The median Epworth sleep score was 3, which is the normal reported range.
      CONCLUSIONS: Although sleep quality is reduced in patients receiving HPN compared
      with aged-matched controls, sleep quality does not seem to be negatively effected
      by cyclic HPN infusion.

PMID- 12005466
TI  - The suffering stranger: medical anthropology and international morality.
AB  - Addressing global inequities has come to define a domain of activist medical
      anthropology called social justice studies. In a recent flagship volume, Dying
      for Growth: Global Inequality and the Health of the Poor, contributors describe
      the effect of global economic trends and neoliberal policies on the destitute and
      disadvantaged. In their advocacy, they use the voices and stories of the poor to
      explain the impact of structural adjustments. This paper uses Dying for Growth as
      an example through which to comment on the wider scholarly trend of using the
      local to validate global claims. The term "suffering stranger" describes those
      iconic figures whose experiences are presented in truncated first-hand accounts
      of suffering in order to validate broader theoretical aims. I argue that the
      suffering stranger masks the real absence of the voices of the poor and their
      suffering on the world stage. There is no international public sphere within
      which these voices might be heard; rather, there is a set of claims about justice
      and human rights. These claims, however, are themselves rooted in cultural values
      and are inextricably woven into global capital. I argue that, in using the voices
      of suffering to further a theoretical agenda, social justice activists assume the
      existence of a public, international domain within which those voices might be
      heard and that, in so doing, they further integrate the poor into destructive
      economic systems. Alongside the work of documenting health inequities, a truly
      effective activism may require assessing and critiquing existing claims of
      international morality.

PMID- 12005467
TI  - Therapeutic itineraries in a global world: Yemenis and their search for
      biomedical treatment abroad.
AB  - Focusing upon how Yemenis travel to Jordan and other countries for medical
      reasons, this article explores a variety of issues and experiences pertaining to
      care-seeking abroad. Topics include state support for treatment outside the
      country, links between countries that facilitate movements, therapeutic
      reputations leading to destination selection, medical travelers' funding and
      logistical decisions, and notions of "good" patient care. The study is set within
      a context of increasing globalization, where advances in communication,
      transportation, and medical devices and procedures all contribute to people's
      ideas about where to go for medical care. As such, it extends care-seeking
      research beyond local services and national boundaries.

PMID- 12005468
TI  - "Looking for children": the search for fertility among the Sara of southern Chad.
AB  - Despite the long history of infertility and childlessness in Central Africa, and
      the ongoing demand for treatment of fertility-related problems, the
      interpretations and experiences of the men and women living in the region vis-a
      vis the inability to have children remain largely unrecorded. In this paper I
      examine what the Sara, one of Chad's largest ethnic groups, have to say about
      fertility problems, and how these views are linked to changes in the social,
      cultural, and economic landscape of southern Chad in the 20th century. I describe
      the iterative and inductive process, commonly referred to by the Sara as "doing
      research," that the Sara use to explore the reasons for the inability to conceive
      or bear children in the face of multiple reproductive threats. The Sara's causal
      constructions convey a holistic and multifaceted perspective on this demographic
      anomaly--a perspective that is missing from most demo graphic and epidemiologic
      accounts and that has important implications for public health policy and
      practice.

PMID- 12005469
TI  - Combined spinal-epidural analgesia for labor: breakthrough or unjustified
      invasion?
AB  - The combined spina-epidural (CSE) technique has become increasingly popular for
      labor analgesia. The advantages of the CSE include more rapid onset of analgesia,
      reduced total drug dosage, minimal or no motor blockade, and increased patient
      satisfaction. CSE has also been associated with more rapid cervical dilation when
      compared to epidural analgesia in nulliparous women in early labor. Despite these
      potential advantages, the indications for CSE versus epidural analgesia remain
      unclear and controversial. This review should allow better understanding of the
      benefits and risks of this technique, and bearing in mind that no ultimate
      neuraxial analgesic exists, it would seem that CSE should be considered a major
      breakthrough in the management of labor analgesia.

PMID- 12005470
TI  - Epidural analgesia: effects on labor progress and maternal and neonatal outcome.
AB  - The intended and unintended effects of epidural labor analgesia are reviewed.
      Mothers randomized to epidural rather than parenteral opioid analgesia have
      better pain relief. Fetal oxygenation is not affected by analgesic method;
      however, neonates whose mothers received intravenous or intramuscular opioids
      rather than epidural analgesia require more naloxone and have lower Apgar scores.
      Epidural analgesia does not affect the rates of cesarean delivery, obstetrically
      indicated instrumented vaginal delivery, neonatal sepsis, or new-onset back pain.
      Epidural analgesia is associated with longer second labor stages, more frequent
      oxytocin augmentation, and maternal fever (particularly among women who shiver
      and women receiving epidural analgesia for > 5 hours) but not with longer first
      labor stages. Epidural analgesia has no affect but intrapartum opioids decrease
      lactation success. Epidural use and urinary incontinence are weakly, but probably
      not causally, associated. Epidural labor analgesia would improve if the
      mechanisms of these unintended effects could be determined.

PMID- 12005471
TI  - Anesthesia for nonobstetric surgery in the pregnant patient.
AB  - Each year over 75,000 pregnant women in the United States undergo nonobstetric
      surgery. The operations include those directly related to pregnancy, such as
      cerclage, those indirectly related to pregnancy, such as ovarian cystectomy, and
      those unrelated to gestation, such as appendectomy. When a pregnant woman
      presents for surgery, it is a stressful event for everyone involved. Issues about
      the surgical problem itself often seem secondary to maternal (and physician)
      concerns about the effect of surgery and anesthesia on the developing fetus, or
      the potential to trigger preterm labor. This article reviews the physiologic and
      anatomic changes that affect anesthetic care during pregnancy. The author also
      reviews the effects of anesthetic drugs and perioperative events on the fetus and
      on the pregnancy outcome. The relatively small number of published series are
      reviewed as well as the controversial recommendations regarding fetal and
      maternal monitoring during surgery.

PMID- 12005472
TI  - Postdural puncture headache in obstetrics.
AB  - Postdural puncture headache (PDPH; or "spinal headache) is the most common
      significant complication from regional anesthesia or analgesia in obstetrics.
      Recent advances in spinal needle design have dramatically decreased the incidence
      of headache after spinal anesthesia, and now the most common cause of PDPH is
      inadvertent puncture of the dura with an epidural needle. The diagnosis and
      treatment of a PDPH should usually be the responsibility of the anesthesiologist,
      but it is important for the obstetrician to be familiar with the clinical course
      and options for therapy, and the usual treatment strategies. This article
      discusses the differential diagnosis of postdelivery headache, the current
      understanding of the pathophysiology of PDPH, options for medical treatment, and
      the controversial issue of whether and when to treat the headache with an
      epidural blood patch.

PMID- 12005473
TI  - Complications associated with regional anesthesia in the obstetric patient.
AB  - The majority of obstetric patients are concerned about labor pains but also have
      fears regarding regional anesthesia and its potential effects on themselves and
      their babies. Anesthesiologists and obstetricians alike must be familiar with
      potential complications of obstetric regional anesthesia and analgesia, and also
      be able to provide the information and reassurance each patient needs. If a
      problem occurs during labor and delivery, it must be dealt with expertly and
      immediately. This article discusses the diagnostic clues, laboratory tests, and
      management of neurologic complications related to obstetric delivery and regional
      anesthesia, as well as the topics of infections, obstetric- and anesthetic
      related neurologic deficits, and special tips on neurologic examination. The most
      common neurologic complication of spinal and epidural anesthesia, postdural
      puncture headache, will not be discussed in detail here.

PMID- 12005474
TI  - New techniques and drugs for epidural labor analgesia.
AB  - Several new techniques and medications are available for epidural labor
      analgesia. Two significant additions are ropivacaine and levobupivacaine. This
      article reviews the current applications of these drugs on the labor ward. The
      clinical implications of patient controlled epidural analgesia and ambulatory
      epidural techniques are discussed. The controversies surrounding epidural test
      dose and fluid preloading are examined.

PMID- 12005475
TI  - Efficient methods of converting hydroxyl groups into amino groups in
      poly(ethylene glycol)-grafted polystyrene resin.

PMID- 12005476
TI  - Palladium-catalyzed synthesis of indole 3-carboxylates on a solid polymer
      support.

PMID- 12005477
TI  - Automated high-throughput synthesis of artificial glycopeptides. Small-molecule
      probes for chemical glycobiology.
AB  - A fully automated method for the synthesis of artificial glycopeptides having two
      (similar or different) carbon-linked glycosyl moieties on a dipeptide scaffold
      has been developed. By use of this approach that combines the diversity of
      peptide/pseudopeptide and glycosides, different glycoside moieties can be
      incorporated onto the peptide/pseudopeptide backbone in a highly controlled
      manner. The approach utilizes a stepwise reductive amination with glycoside
      aldehyde derivatives (model 1) or (ii) glycoside reductive amination followed by
      glycoside amide bond formation (model 2). Further, an automated method has been
      utilized in the high-throughput library synthesis of 4 x 96 artificial
      glycopeptides. These libraries were tested as chemical probes/inhibitors of
      enzyme systems that convert a glucose moiety into rhamnose prior to incorporation
      of the rhamnose unit and the conversion of UDP-galactopyranose to UDP
      galactofuranose via UDP-galactopyranose mutase enzyme during the biosynthesis of
      the mycobacterium cell wall.

PMID- 12005478
TI  - Optimization of reaction conditions for REM resin-bound quaternization reactions.
AB  - A study into the effect of reaction variables on the quaternization of REM resin
      bound tertiary amines was undertaken. The influence of resin matrix, solvent,
      reaction time, temperature, and amount of quaternization agent on the outcome of
      reaction was evaluated by reaction monitoring using (19)F NMR. The highest yields
      of tertiary amine products were seen when DMSO was used as reaction solvent in
      conjunction with a reaction time of 18 h at room temperature. The use of heating
      for extended reaction times tended to depress yields, indicating product cleavage
      during quaternization. Quaternization on PS-DVB resin was found to be more robust
      than reaction on PS-PEG matrices where yields were generally considerably lower
      than the observed conversions. DMSO was the most efficient reaction solvent for
      both resins despite poor swelling of the quaternization starting material.

PMID- 12005479
TI  - Comparative resin kinetics using in situ fluorescence measurements.
AB  - The aminolysis of a novel activated ester resin was utilized for kinetic study
      via continuous in situ fluorescence measurements. A variety of resin compositions
      (polystyrene, JandaJel, ArgoPore, TentaGel, NovaGel, and PEGA) and solvents
      (dimethylformamide, acetonitrile, tetrahydrofuran, 1,2-dichlorethane, and
      toluene) were tested to compare their effects on the reaction rate. A linear
      relationship between the reaction rate and (solvent polarity x swelling of resin)
      was elucidated for the aminolysis reaction.

PMID- 12005480
TI  - Solid-phase synthesis of 1,2,5-trisubstituted 4-imidazolidinones.
AB  - An efficient method for the preparation of 1,2,5-trisubstituted 4
      imidazolidinones is presented. The synthetic approach is based on the formation
      of an N-[1-(benzotriazol-1-yl)alkyl] moiety on the amino group of a MBHA resin
      bound amino acid. The nucleophilic substitution of the benzotriazole group with
      an amidic nitrogen results in the formation of a five-membered imidazolidinone
      ring. The reaction is nonstereospecific and produces diastereomers in ratios that
      vary depending on the substituents on the ring. A variety of N-alpha-alkylated
      amino acids were cyclized with aromatic, aliphatic, and heterocyclic aldehydes to
      determine optimal reaction conditions and to select building blocks for the
      future preparation of a large, diverse range of individual trisubstituted
      imidazolidinones as well as a mixture-based combinatorial library.

PMID- 12005481
TI  - Novel approaches for the solid-phase synthesis of biheterocyclic dihydroimidazole
      analogues.
AB  - The solid-phase syntheses of dihydroimidazolyl 2-alkylthiobenzimidazoles,
      dihydroimidazolyl 2-alkylsulfonylbenzimidazoles, dihydroimidazolyl
      dihydroquinoxalin-2,3-diones, and dihydroimidazolyl dihydrobenzimidazol-2-imines
      are described. Following reduction of a resin-bound amino acid amide, the primary
      amine of the resulting resin-bound diamine was N-acylated with 4-fluoro-3
      nitrobenzoic acid. Treatment with POCl3 led to formation of a dihydroimidazole
      derivative via dehydrative cyclization. The resin-bound dihydroimidazole
      derivative was then used as the key starting material for the synthesis of the
      aforementioned biheterocycles. Following cleavage, the resulting compounds,
      obtained in moderate yield and good purity, were characterized by LC-MS and 1H
      NMR and 13C NMR spectroscopy.

PMID- 12005482
TI  - The ortho backbone amide linker (o-BAL) is an easily prepared and highly acid
      labile handle for solid-phase synthesis.
AB  - The tris(alkoxy)benzyl backbone amide linker (BAL) has found widespread
      application in solid-phase synthesis. The key intermediate for preparation of
      para BAL (p-BAL) is 2,6-dimethoxy-4-hydroxybenzaldehyde; several reports on its
      synthesis have appeared. However, the ortho analogue of the handle (o-BAL) has
      successfully been used by us for the synthesis of C-terminal-modified peptides,
      oligosaccharides, and substituted anilines. Here, we present a new and convenient
      synthesis of the key intermediate for o-BAL, 4,6-dimethoxy-2-hydroxybenzaldehyde,
      by a highly regioselective demethylation with BBr3, followed by purification
      through steam distillation. Cleavage studies of Leu-enkephalin anchored to either
      o-BAL or p-BAL handles revealed that both handles were surprisingly acid-labile
      and released the peptide with dilute TFA (5% and even 1% TFA in CH2Cl2). This
      useful property allowed the synthesis of fully protected Leu-enkephalin. The very
      convenient synthesis of 4,6-dimethoxy-2-hydroxybenzaldehyde combined with the
      benign properties of the o-BAL handle may make it the preferred regioisomer.

PMID- 12005483
TI  - Solution-phase library synthesis of furanoses.
AB  - The solution-phase synthesis of amido-, urea-, and aminofuranoses was achieved.
      Alkylated furanose aldehydes were treated with primary amines in the presence of
      sodium triacetoxyborohydride to give secondary amines. Subsequent acylation with
      acid chlorides and isocyanates afforded amidofuranoses and ureafuranoses,
      respectively. Second, reductive amination of furanose aldehydes with secondary
      amines yielded tertiary amines. The resulting acetonides were treated with
      alcohols in the presence of acid to yield mixed acetals. In the library
      syntheses, functionalized scavenger resins were used in the purification of
      intermediates and products.

PMID- 12005484
TI  - Palladium(0)-catalyzed coupling-cyclization reaction of polymer-supported aryl
      iodides with 1,2-allenyl carboxylic acids. Solid-phase parallel synthesis of
      butenolides.
AB  - In this contribution, we constructed a library of butenolides with 77 members by
      parallel synthesis strategy on Merrifield resin. Sixteen 2,3-allenoic acids and
      12 polymer-bound aryl iodides were combined to react with each other, and then
      the polymer-supported products were cleaved to release butenolide derivatives.
      The reactions with alkyl-substituted 2,3-allenoic acids in acetonitrile afforded
      the corresponding products in high yields and high purities, whereas those with
      aryl-substituted acids in acetonitrile failed. After some reaction conditions
      were screened, the solid-phase reactions with aryl-substituted 2,3-allenoic acids
      were realized in toluene, and the products are of good purities albeit in
      slightly low yields. In the benzyl ether linkage, a new cleavage model was found.
      By adding 6 equiv of acetyl bromide, we can get single (5-oxo-2,5-dihydrofuran-3
      yl)benzyl bromide other than the corresponding benzyl acetate. To further
      increase the diversities, a dihydropyran (DHP) linker was introduced into our
      combinatorial synthesis of butenolides. By reversing the addition sequence of 2,3
      allenoic acids and organic base, we realized the solid-phase cyclization reaction
      of polymer-bound aryl iodides with the THP linkage in moderate yields and good
      purities. Now the library of butenolides includes (5-oxo-2,5-dihydrofuran-3
      yl)benzoic acids, -aryl acetates, -benzyl bromides, -benzyl alcohols, and 
      phenols, which are difficult to synthesize with conventional solution methods.

PMID- 12005485
TI  - Design and spectroscopic characterization of peptide models for the plastocyanin
      copper-binding loop.
AB  - The Cu(II)- and Co(II)-binding properties of two peptides, designed on the basis
      of the active site sequence and structure of the blue copper protein
      plastocyanin, are explored. Peptide BCP-A, Ac-Trp-(Gly)(3)-Ser-Tyr-Cys-Ser-Pro
      His-Gln-Gly-Ala-Gly-Met-(Gly )(3)-His-(Gly)(2)-Lys-CONH(2), conserves the Cu
      binding loop of plastocyanin containing three of the four copper ligands and has
      a flexible (Gly)(3) linker to the second His ligand. Peptide BCP-B, Ac-Trp
      (Gly)(3)-Cys-Gly-His-Gly-Val-Pro-Ser-His-Gly-Met-Gly-CONH(2), contains all four
      blue copper ligands, with two on either side of a beta-turn. Both peptides form
      1:1 complexes with Cu(II) through His and Cys ligands. BCP-A, the ligand loop,
      binds to Cu(II) in a tetrahedrally distorted square plane with axial solvent
      ligation, while BCP-B-Cu(II) has no tetrahedral distortion in aqueous solution.
      In methanolic solution, distortion of the square plane is evident for both BCP
      Cu(II) complexes. Tetrahedral Co(II) complexes are observed for both peptides in
      aqueous solution but with 4:2 peptide:Co(II) stoichiometries as estimated by
      ultracentrifugation. Cu(II) reduction potentials for the aqueous peptide-Cu(II)
      complexes were measured to be +75 +/- 30 mV vs NHE for BCP-A-Cu(II) and -10 +/-
      20 mV vs NHE for BCP-B-Cu(II). The results indicate that the plastocyanin ligand
      loop can act as a metal-binding site with His and Cys ligands in the absence of
      the remainder of the folded protein but, by itself, cannot stabilize a type 1
      copper site, emphasizing the role of the protein matrix in protecting the Cu
      binding site from solvent exposure and the Cys from oxidation.

PMID- 12005486
TI  - Cyclometalated products of [(COE)(2)RhCl](2) and 1,3-(RSCH(2))(2)C(6)H(4) (R =
      (t)Bu, (i)Pr) Are Dimeric. Synthesis, molecular structures, and solution dynamics
      of [mu-ClRh(H)(RSCH(2))(2)C(6)H(3)-2,6](2).
AB  - Two tridentate thioether pincer ligands, 1,3-(RSCH(2))(2)C(6)H(4) (R = (t)()Bu,
      1a; R = (i)()Pr, 1b) underwent cyclometalation using [(COE)(2)RhCl](2) in
      air/moisture-free benzene at room temperature. The resultant complexes, [mu
      ClRh(H)(RSCH(2))(2)C(6)H(3)-2,6](2) (R = (t)Bu, 2a; R = (i)Pr, 2b) are dimeric
      both in the solid state and in solution. A battery of variable-temperature one-
      and two-dimensional (1)H NMR experiments showed conclusively that both complexes
      undergo dynamic exchange in solution. Exchange between two dimeric diastereomers
      of 2a in solution occurred via rotation about the Rh-C(ipso) bond. The dynamic
      exchange of 2b was significantly more complex as an additional exchange
      mechanism, sulfur inversion, occurred, which resulted in the exchange between
      several diastereomers in solution.

PMID- 12005487
TI  - Electrochemistry and photoelectron spectroscopy of oxomolybdenum(V) complexes
      with phenoxide ligands: effect of para substituents on redox potentials,
      heterogeneous electron transfer rates, and ionization energies.
AB  - Complexes of the form (Tp*)MoOCl(p-OC(6)H(4)X) and (Tp*)MoO(p-OC(6)H(4)X)(2) (Tp*
      = hydrotris(3,5-dimethyl-1-pyrazolyl)borate and X = OEt, OMe, Et, Me, H, F, Cl,
      Br, I, and CN) were examined by electrochemical techniques and gas-phase
      photoelectron spectroscopy to probe the effect of the remote substituent (X) on
      electron-transfer reactions at the oxomolybdenum core. Cyclic voltammetry
      revealed that all of these neutral Mo(V) compounds undergo a quasireversible one
      electron oxidation (Mo(VI)/Mo(V)) and a quasireversible one-electron reduction
      (Mo(V)/Mo(IV)) at potentials that linearly depend on the electronic influence
      (Hammett sigma(p) parameter) of X. The first ionization energies for (Tp*)MoO(p
      OC(6)H(4)X)(2) (X = OEt, OMe, H, F, and CN) were determined by photoelectron
      spectroscopy. A nearly linear correlation was found for the Mo(VI)/Mo(V)
      oxidation potentials in solution and the gas-phase ionization energies.
      Calculated heterogeneous electron-transfer rate constants show a slight
      systematic dependence on the substituent.

PMID- 12005488
TI  - Comparative study of structure-properties relationship for novel beta-halogenated
      lanthanide porphyrins and their nickel and free bases precursors, as a function
      of number and nature of halogens atoms.
AB  - The synthetic route of partially beta-halogenated via a "metal-assisted" reaction
      and perhalogenated terbium complexes is described. This protocol allows the
      facile insertion of the halogens (bromines or chlorides) to the porphyrin
      peripheral positions. The electronic absorption spectra and the redox potentials
      of the free porphyrins as well as the terbium complexes are dramatically affected
      as the number of halogen atoms increase. In fact, two antagonistic effects are
      responsible for that, the inductive and the distortion effects on the porphyrin
      ring. They result in a red shift for the Soret band and a
      stabilization/destabilization of the HOMOs/LUMOs which in turn is manifested by
      variations on the redox potentials. The novel crystal structure of the
      Ni(Cl(8)TPP) is discussed in great detail and compared with the previously
      reported structures of Tb(Cl(8)TPP) (OAc)(DMSO)(2) x 3PhCH(3) x MeOH and
      H(2)(Br(8)TPP), as well as with other perhalogenated nickel porphyrins available
      in the literature.

PMID- 12005489
TI  - Statistical and molecular mechanics analysis of the effects of changing donor
      type on bond length in the two series [Co(III)N(n)O(6-n)] and [Ni(II)N(n)O(6-n)]
      (n = 0-6): a new route to bond-stretch Parameters.
AB  - Changes in bond lengths across the series of complexes [Co(III)N(n)O(6-n)] and
      [Ni(II)N(n)O(6-n)], (n = 0-6) have been examined by a statistical analysis of the
      bond lengths in 256 Co(III) and 205 Ni(II) complexes. In both cases a systematic
      reduction in both metal-N and metal-O bond lengths is observed as oxygen donors
      replace nitrogen in the coordination sphere. In the case of Co(III), the
      reduction in bond lengths is linear across the series, whereas, in the case of
      Ni(II), it is more asymptotic in nature. It was found that this systematic change
      to the inner coordination sphere produced a much larger range of bond lengths
      than had previously been observed by changes to the outer sphere. The trends
      across the two series were reproduced using molecular mechanics; however, the
      magnitude of the change was not initially predicted correctly in either case.
      Alterations to molecular mechanics parameters that reproduced the trends in the
      [Co(III)N(n)O(6-n)] series also resulted in a significant overall improvement in
      the predictions of Co(III)-N bond lengths in a series of Co(III) hexaamines, with
      all being reproduced within 0.006 A. This improvement was taken as an indication
      that the bond-length reduction across the series is largely steric in origin.

PMID- 12005490
TI  - Synthesis, characterization, and structure of [[PtMe(3)(9-MeA)](3)] (9-MeAH = 9
      Methyladenine): a cyclic trimeric platinum(IV) complex with a nucleobase.
AB  - Reaction of [[PtMe(3)I](4)] with AgOAc in acetone results in formation of
      trimethylplatinum(IV) acetate (1) that reacts with 9-methyladenine (9-MeAH) in
      ratio 1:1 with its deprotonation yielding a trimethyl(9
      methyladeninato)platinum(IV) complex (2) that was obtained from acetone/diethyl
      ether as [[PtMe(3)(9-MeA)](3)] x Me(2)CO (2a) and from chloroform/diethyl ether
      as [[PtMe(3)(9-MeA)](3)] x 1.5Et(2)O x 2H(2)O (2b). Single-crystal X-ray
      investigations revealed that 2a and 2b in the solid state form cyclic trimeric
      molecules in which three PtMe(3) moieties are bridged by deprotonated 9
      methyladenine ligands in mu-kappa N(1):kappa(2)N(6),N(7) coordination mode. The
      methyladeninato ligands include angles with the plane defined by the Pt(3) unit
      between 55.9(3) degrees and 66.6(3) degrees. Thus, the structures of the cyclic
      trimers resemble hollow truncated cones. Crystals of the acetone solvate 2a
      consist of stacks of unidirectional trimeric molecules; the solvate acetone
      molecules lie between the trimers. In the crystals of complex 2b, the trimeric
      molecules are arranged head-to-head, and the cavity between is filled with four
      water molecules. Complex 2 was also fully characterized by (1)H, (13)C, and
      (195)Pt NMR spectroscopies. The existence of the cyclic trimeric structure of
      complex 2 in acetone solution was confirmed by ESI mass spectrometry exhibiting
      the protonated trimeric complex [[tMe(3)(9-MeA)]3)H](+) [2 + H](+) (m/z 1165) as
      base peak. CID experiments of that parent ion showed as main fragmentation
      processes loss of two methyl ligands (probably as ethane) and cleavage of a
      methyladenine ligand.

PMID- 12005491
TI  - Mechanism of silver-promoted ligand metathesis in square-planar complexes of d(8)
      Ions. Kinetics of formation and molecular structures of a trinuclear intermediate
      [(Me)(N-N)Pt(mu-Cl)Ag(mu-Cl)Pt(N-N)(Me)](+) and its dinuclear evolution product
      [(Me)(N-N)Pt(mu-Cl)Pt(N-N)(Me)](+) (N-N = ArN=C(Me)C(Me)=NAr, Ar = 2,6-(i
      Pr)(2)C(6)H(3)).
AB  - The silver-assisted ligand metathesis reaction involving a platinum(II) complex
      of formula [PtClMe(N,N-chelate)] with acetonitrile has been investigated. By
      using a suitably hindered N,N-chelate, an otherwise hardly detectable trinuclear
      species has been isolated and characterized through X-ray diffractometry. The
      trinuclear cation consists of two nearly orthogonal [PtCl(Me)(N,N-chelate)]
      square-planar units entrapping an Ag(+) cation through the chloride ligands that,
      acting as bidentate, form a linear AgCl(2) unit with two nonequivalent Ag-Cl
      bonds. The residual acidity of the silver cation is satisfied by one secondary Ag
      Pt interaction [Ag-Pt(1) = 2.82 A] in which the platinum atom acts as a donor.
      Kinetic studies have demonstrated that the silver assistance operates both
      through a simple associative step and through a pathway in which the above
      trinuclear complex is an active intermediate. In a noncoordinating solvent the
      latter species evolves with AgCl loss and formation of a dinuclear Pt,Pt complex
      showing a rare single chloride bridge.

PMID- 12005492
TI  - Photolytic reactions of subvalent aluminum(I) halides in the presence of
      dioxygen: generation and characterization of the peroxo species XAlO(2) and
      XAl(mu-O)(2)AlX (X = F, Cl, Br).
AB  - The photolytic reactions of AlX (X = F, Cl, and Br) with O(2) in solid argon
      matrixes are shown to yield the peroxo species XAlO(2), all exhibiting C(2)(v)()
      symmetry. The species were identified and characterized by means of IR
      spectroscopy allied with quantum mechanical calculations. In addition to singlet
      XAlO(2) as the main product of the reaction of AlX, the experiments give clear
      evidence for the formation of XAl(mu-O)(2)AlX, by the reaction of the dimer
      (AlX)(2), which is also known to be present in the matrixes upon deposition.
      Finally, weak IR absorptions were tentatively assigned to XAlO(2) in its triplet
      electronic state. According to our calculations, the singlet-triplet gap amounts
      to about 40 kJ mol(-1) for all species. The properties of the peroxide species
      invite comparison with previously investigated dioxygen complexes, as well as the
      superoxide species XAlOO and various possible products of the reaction of
      (AlX)(2) dimers.

PMID- 12005493
TI  - Mossbauer study of the three-coordinate planar Fe(II) thiolate complex
      [Fe(SR)(3)](-) (R = C(6)H(2)-2,4,6-tBu(3)): model for the trigonal iron sites of
      the MoFe(7)S(9):homocitrate cofactor of nitrogenase.
AB  - The cofactor (M-center) of the MoFe protein of nitrogenase, a
      MoFe(7)S(9):homocitrate cluster, contains six Fe sites with a (distorted)
      trigonal sulfido coordination. These sites exhibit unusually small quadrupole
      splittings, Delta E(Q) approximately 0.7 mm/s, and isomer shifts, delta
      approximately 0.41 mm/s. Mossbauer and ENDOR studies have provided the magnetic
      hyperfine tensors of all iron sites in the S = 3/2 state M(N). To assess the
      intrinsic zero-field splittings and hyperfine parameters of the cofactor sites,
      we have studied with Mossbauer spectroscopy two salts of the three-coordinated
      Fe(II) thiolate complex [Fe(SR)(3)](-) (R = C(6)H(2)-2,4,6-tBu(3)). One of the
      salts, [Ph(4)P][Fe(SR)(3)] x 2MeCN x C(7)H(8), 1, has a planar geometry with
      idealized C(3h) symmetry. This S = 2 complex has an axial zero-field splitting
      with D = +10.2 cm(-1). The magnetic hyperfine tensor components A(x) = A(y) = 
      7.5 MHz and A(z) = -29.5 MHz reflect an orbital ground state with d(z(2))
      symmetry. A(iso) = (A(x) +A(y) +A(z))/3 = -14.9 MHz, which includes the contact
      interaction (kappa P = -21.9 MHz) and an orbital contribution (+7 MHz), which is
      substantially smaller than A(iso) approximately -22 MHz of the tetrahedral
      Fe(II)(S-R)(4) sites of both rubredoxin and [PPh(4)](2)[Fe(II)(SPh)(4)]. The
      largest component of the electric field gradient (EFG) tensor is negative, as
      expected for a d(z(2)) orbital. However, Delta E(Q) = -0.83 mm/s, which is
      smaller than expected for a high-spin ferrous site. This reduction can be
      attributed to a ligand contribution, which in planar complexes provides a large
      positive EFG component perpendicular to the ligand plane. The isomer shift of 1,
      delta = 0.56 mm/s, approaches the delta-values reported for the six trigonal
      cofactor sites. The parameters of 1 and their importance for the cofactor cluster
      of nitrogenase are discussed.

PMID- 12005494
TI  - Further evidence for the tetraoxoiodate(V) anion, IO(4)(3-): hydrothermal
      syntheses and structures of Ba[(MoO(2))(6)(IO(4))(2)O(4)] x H(2)O and
      Ba(3)[(MoO(2))(2)(IO(6))(2)] x 2H(2)O.
AB  - The hydrothermal reaction of MoO(3) with BaH(3)IO(6) at 180 degrees C for 3 days
      results in the formation of Ba[(MoO(2))(6)(IO(4))(2)O(4)] x H(2)O (1). Under
      similar conditions, the reaction of Ba(OH)(2) x 8H(2)O with MoO(3) and
      Ba(IO(4))(2) x 6H(2)O yields Ba(3)[(MoO(2))(2)(IO(6))(2)] x 2H(2)O (2). The
      structure of 1, determined by single-crystal X-ray diffraction, consists of
      corner- and edge-sharing distorted MoO(6) octahedra that create two-dimensional
      slabs. Contained within this molybdenum oxide framework are approximately C(2v)
      tetraoxoiodate(V) anions, IO(4)(3-), that are involved in bonding with five
      Mo(VI) centers. The two equatorial oxygen atoms of the IO(4)(3-) anion chelate a
      single Mo(VI) center, whereas the axial atoms are mu(3)-oxo groups and complete
      the octahedra of four MoO(6) units. The coordination of the tetraoxoiodate(V)
      anion to these five highly electropositive centers is probably responsible for
      stabilizing the substantial anionic charge of this anion. The Ba(2+) cations
      separate the layers from one another and form long ionic contacts with
      neighboring oxygen atoms and a water molecule. Compound 2 also contains distorted
      MoO(6) octahedra. However, these solely edge-share with octahedral
      hexaoxoiodate(VII), IO(6)(5-), anions to form zigzagging one-dimensional,
      (1)(infinity)[(MoO(2))(IO(6))](3-), chains that are polar. These chains are
      separated from one another by Ba(2+) cations that are coordinated by additional
      water molecules. Bond valence sums for the iodine atoms in 1 and 2 are 5.01 and
      7.03, respectively. Crystallographic data: 1, monoclinic, space group C2/c, a =
      13.584(1) A, b = 7.3977(7) A, c = 20.736(2) A, beta = 108.244(2) degrees, Z = 4;
      2, orthorhombic, space group Fdd2, a = 13.356(7) A, b = 45.54(2) A, c = 4.867(3)
      A, Z = 8.

PMID- 12005495
TI  - Modeling dioxygen-activating centers in non-heme diiron enzymes: carboxylate
      shifts in diiron(II) complexes supported by sterically hindered carboxylate
      ligands.
AB  - General synthetic routes are described for a series of diiron(II) complexes
      supported by sterically demanding carboxylate ligands 2,6-di(p-tolyl)benzoate
      (Ar(Tol)CO(2)(-)) and 2,6-di(4-fluorophenyl)benzoate (Ar(4-FPh)CO(2)(-)). The
      interlocking nature of the m-terphenyl units in self-assembled [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)L(2)] (L = C(5)H(5)N (4); 1-MeIm (5)) promotes
      the formation of coordination geometries analogous to those of the non-heme
      diiron cores in the enzymes RNR-R2 and Delta 9D. Magnetic susceptibility and
      Mossbauer studies of 4 and 5 revealed properties consistent with weak
      antiferromagnetic coupling between the high-spin iron(II) centers. Structural
      studies of several derivatives obtained by ligand substitution reactions
      demonstrated that the [Fe(2)(O(2)CAr')(4)L(2)] (Ar' = Ar(Tol); Ar(4-FPh)) module
      is geometrically flexible. Details of ligand migration within the
      tetracarboxylate diiron core, facilitated by carboxylate shifts, were probed by
      solution variable-temperature (19)F NMR spectroscopic studies of [Fe(2)(mu
      O(2)CAr(4-FPh))(2)-(O(2)CAr(4-FPh))(2)(THF)(2)] (8) and [Fe(2)(mu-O(2)CAr(4
      FPh))(4)(4-(t)BuC(5)H(4)N)(2)] (12). Dynamic motion in the primary coordination
      sphere controls the positioning of open sites and regulates the access of
      exogenous ligands, processes that also occur in non-heme diiron enzymes during
      catalysis.

PMID- 12005496
TI  - The lacunary polyoxoanion synthon alpha-P(2)W(15)O(56)(12-): an investigation of
      the key variables in its synthesis plus multiple control reactions leading to a
      reliable synthesis.
AB  - A reliable way to determine the purity of the kinetically precipitated,
      noncrystalline lacunary polyoxoanion alpha-P(2)W(15)O(56)(12-) has been
      developed, namely, the conversion of alpha-P(2)W(15)O(56)(12-) into the tri
      Nb(5+)- and V(5+)-containing polyoxoanions P(2)W(15)Nb(3)O(62)(9-) and
      P(2)W(15)V(3)O(62)(9-), respectively, followed by quantitative analysis of their
      purity by (31)P-NMR prior to recrystallization. With this previously
      unappreciated, straightforward alpha-P(2)W(15)O(56)(12-) purity-assessment
      methodology in hand, the five reported literature syntheses of alpha
      P(2)W(15)O(56)(12-) are investigated with an emphasis on understanding the
      effects of the five differing variables within these syntheses (the amount of
      Na(2)CO(3) base, the rate of addition of the base, the reaction temperature, the
      reaction scale, and the product drying method). Two methods of Nb(5+) addition
      (Nb(6)O(19)(8-) and NbCl(5)) to yield P(2)W(15)Nb(3)O(62)(9-) are also evaluated,
      as is the issue of whether any purification is provided by the normally optimum
      strategy of first preparing a water-soluble salt and its crystallization from
      water (here the (CH(3))(4)N(+) salt of the Nb-O-Nb bridged anhydride,
      P(4)W(30)Nb(6)O(123)(16-)), followed by its conversion to the organic-solvent
      soluble, but noncrystalline, (n-C(4)H(9))(4)N(+) salt, [(n
      C(4)H(9))(4)N](9)[P(2)W(15)Nb(3)O(62)]. The results yield five previously
      unavailable and unequivocal insights: (1) Only the amount of added Na(2)CO(3)
      base affects the purity or yield of the desired alpha-P(2)W(15)O(56)(12-); the
      amount of added base is key, however. (2) Contant's 1990 Inorganic Syntheses
      procedure provides the highest-purity alpha-P(2)W(15)O(56)(12-) presently
      available. (3) All prior syntheses calling for the addition of base to
      P(2)W(18)O(62)(6-) until pH 9 must be abandoned. (4) The purity of even Contant's
      alpha-P(2)W(15)O(56)(12-) is only 90%. (5) An identifiable impurity is the 16
      tungsten polyoxoanion, alpha-P(2)W(16)()O(59)(12-). Also identified and
      summarized are multiple compounding errors in the observation of, reporting on,
      and thinking about the synthesis of alpha-P(2)W(15)O(56)(12-) historically,
      errors which delayed the most reliable synthesis of alpha-P(2)W(15)O(56)(12-)
      from being identified for 18 years (from the 1983 discovery of alpha
      P(2)W(15)O(56)(12-)). However, these errors yield valuable take-home lessons for
      anyone interested in working in this demanding area of inorganic synthetic
      chemistry, where direct structural methods for identifying the products and their
      purity, such as the lacunary polyoxoanion synthon alpha-P(2)W(15)O(56)(12-),
      sometimes simply do not exist.

PMID- 12005497
TI  - Synthesis, NMR, and X-ray crystallographic analysis of C-hydrazino-C
      carboxycarboranes: versatile ligands for the preparation of BNCT and BNCS agents
      and (99m)Tc radiopharmaceuticals.
AB  - Protected hydrazine derivatives of ortho-, meta-, and para-carboranes were
      synthesized in good to excellent yields by reacting the mono-lithio salts of the
      respective carboranes with di-tert-butyl azodicarboxylate (DBAD). Subsequent
      deprotonation of the remaining carborane CH group, followed by the addition of
      CO(2)(g), resulted in the formation of bifunctional C-hydrazino-C
      carboxycarboranes in good to excellent overall yields. Crystal structures of the
      monosubstituted ortho-carborane, 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,2
      dicarba-closo-dodecaborane (8) [a = 21.213(6) A, b = 10.498(3) A, c = 9.866(2) A,
      alpha = gamma = 90 degrees, beta = 90.529(4) degrees ] and the bifunctional para
      carborane 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,12-dicarba-closo
      dodecaborane-12-carboxylic acid (3) [a = 12.744(10) A, b = 12.875(9) A, c =
      14.767(9) A, alpha = beta = gamma = 90 degrees ] were obtained. Intermolecular
      hydrogen bonding was a dominant packing feature in both structures. The reported
      compounds represent a unique class of bifunctional carboranes that can be used in
      peptidomimetic research and as synthons to prepare novel radiopharmaceuticals and
      boron neutron capture therapy/boron neutron capture synovectomy (BNCT/BNCS)
      agents.

PMID- 12005498
TI  - Synthesis and structure of singly bridged and doubly bridged [MoFe(3)S(4)] double
      cubanes with bidentate phosphine ligands.
AB  - The reactions of the (Et(4)N)(2)[(Cl(4)-cat)(MeCN)MoFe(3)S(4)Cl(3)] (I) cluster
      with Fe(pp)(2)Cl(2) (pp = depe (bis(1,2-diethylphosphino)ethane) or dmpe (bis(1,2
      dimethylphosphino)ethane)) produced the [(Cl(4)-cat)MoFe(3)S(4)(pp)(2)Cl](2)(mu
      pp) (pp = depe (III) or dmpe (V)) singly bridged double cubanes. The reactions of
      I with the same bidentate phosphine ligands in the presence of NaBPh(4) also
      produced III and the [(Cl(4)-cat)MoFe(3)S(4)(dmpe)(2)](2)(mu-S)(mu-dmpe) (VI)
      doubly bridged double cubane, respectively. The byproduct
      (BPh(4))[Fe(dmpe)(2)(MeCN)Cl] (VII) has been isolated from the reaction mixture
      and crystallographically characterized. The depe analogue of VI, [(Cl(4)
      cat)MoFe(3)S(4)(depe)(2)](2)(mu-S)(mu-depe) (IV), has been successfully prepared
      from III in the presence of excess Li(2)S. Similar reactions with
      (Et(4)N)(2)[Fe(4)S(4)(SPh)(4)] (VIII) have resulted in the formation of the
      neutral Fe(4)S(4)(depe)(2)(SPh)(2) (IX) cluster. The chloride analogue of IX,
      Fe(4)S(4)(depe)(2)Cl(2) (XI), has been obtained by a reaction of IX with benzoyl
      chloride. The crystal and molecular structures of III, VI, VII, and XI have been
      determined by single-crystal X-ray crystallography. The electrochemical and
      spectroscopic properties, including the Mossbauer spectra of the new clusters,
      have been determined and analyzed.

PMID- 12005499
TI  - Formation and structure of 1:1 complexes between aryl hydroxamic acids and
      vanadate at neutral pH.
AB  - Although aryl hydroxamic acids are well-known to form coordination complexes with
      vanadate (V(V)), the nature of these complexes at neutral pH and submillimolar
      concentrations, the conditions under which such complexes inhibit various serine
      amidohydrolases, is not well established. A series of qualitative and
      quantitative experiments, involving UV/vis, (1)H NMR, and (51)V NMR
      spectroscopies, established that both 1:1 and 1:2 vanadate/hydroxamate complexes
      form at pH 7.5, with the former dominating at submillimolar concentrations.
      Formation constants for the complexes of several aryl and alkyl hydroxamic acids
      were determined; for example, for benzohydroxamic acid, the stepwise formation
      constants of the 1:1 and 1:2 complexes were 3000 and 400 M(-1), respectively. The
      (51)V chemical shift of the 1:1 4-nitrobenzohydroxamic acid complex was -497 ppm,
      and that of its unsubstituted analogue was -498 ppm. A (1)H-(15)N HSQC spectrum
      of the 4-nitrobenzo-(15)N-hydroxamic acid/vanadate complex indicated the presence
      of an N-H group with (15)N and (1)H chemical shifts of 115 and 5.83 ppm,
      respectively. A (13)C NMR spectrum of the complex of 4-nitrobenzo-(13)C
      hydroxamic acid with vanadate displayed a resonance at 170.1 ppm and thus a
      coordination-induced shift (CIS) of +3.8 ppm. In contrast, the CIS value of an
      established 1:2 complex, thought to contain chelated hydroxamic acid ligands, was
      +11.9 ppm. These spectral data led to the following structural picture of 1:1
      complexes of vanadate and aryl hydroxamic acids. They contain penta- or hexa
      coordinated vanadium. The ligand is in the hydroxamate rather than hydroximate
      form. The ligand is presumably bound to vanadium through the hydroxamic hydroxyl
      oxygen, but the hydroxamic acid carbonyl oxygen interacts weakly with vanadium.
      These species are the most likely candidates for the inhibitors of serine
      amidohydrolases found in vanadate/hydroxamic acid mixtures.

PMID- 12005500
TI  - Unusual reactivity of methylene group adjacent to pyridine-2-carboxamido moiety
      in iron(III) and cobalt(III) complexes.
AB  - The Fe(III) and Co(III) complexes of the ligand N-(2-picolyl)picolinamide (pmpH;
      H represents the dissociable amide hydrogen), namely, [Fe(pmp)(2)]BF(4) (1) and
      [Co(pmp)(2)]ClO(4) (2), have been synthesized and structurally characterized. The
      [bond]CH(2)[bond] moiety of pmp(-) in [M(pmp)(2)](+) (M = Fe, Co) is very
      reactive and is readily converted to carbonyl (C[double bond]O) group upon
      exposure to dioxygen. Such conversion results in [M(bpca)(2)]ClO(4) complexes (M
      = Fe (3), Co (5); bpcaH = bis(2-pyridylcarbonyl)amine) which have been
      characterized by spectroscopy and X-ray diffraction. The structure of 5 is
      reported here for the first time. The reactivity of the [bond]CH(2)[bond] moiety
      of pmp(-) has so far precluded the isolation of 1 although other metal complexes
      of pmp(-) have been reported years ago. The CH(2) --> C[double bond]O
      transformation arises from the tendency of the coordinated pmp(-) ligand to
      achieve further conjugation in the ligand framework and provides a better way to
      synthesize the metal complexes of bpcaH ligand. Reaction of 3 with NaH affords
      Fe(II) complex [Fe(bpca)(2)] (4) without any reduction of the ligand frame.

PMID- 12005501
TI  - Effects of solvents on the electron configurations of the low-spin dicyano[meso
      tetrakis(2,4,6-triethylphenyl)porphyrinato]iron(III) complex: importance of the C
      H...N weak hydrogen bonding.
AB  - There are two types of electron configurations, (d(xy))(2)(d(xz), d(yz))(3) and
      (d(xz), d(yz))(4)(d(xy))(1), in low-spin iron(III) porphyrin complexes. To reveal
      the solvent effects on the ground-state electron configurations, we have examined
      the (13)C- and (1)H-NMR spectra of low-spin dicyano[meso-tetrakis(2,4,6
      triethylphenyl)porphyrinato]ferrate(III) in a variety of solvents, including
      protic, dipolar aprotic, and nonpolar solvents. On the basis of the NMR study, we
      have reached the following conclusions: (i) the complex adopts the ground state
      with the (d(xz), d(yz))(4)(d(xy))(1) electron configuration, the (d(xz),
      d(yz))(4)(d(xy)())(1) ground state, in methanol, because the d(pi) orbitals are
      stabilized due to the O-H...N hydrogen bonding between the coordinated cyanide
      and methanol; (ii) the complex also exhibits the (d(xz), d(yz))(4)(d(xy))(1)
      ground state in nonpolar solvents, such as chloroform and dichloromethane, which
      is ascribed to the stabilization of the d(pi) orbitals due to the C-H...N weak
      hydrogen bonding between the coordinated cyanide and the solvent molecules; (iii)
      the complex favors the (d(xz), d(yz))(4)(d(xy))(1) ground state in dipolar
      aprotic solvents, such as DMF, DMSO, and acetone, though the (d(xz),
      d(yz))(4)(d(xy))(1) character is less than that in chloroform and
      dichloromethane; (iv) the complex adopts the (d(xy))(2)(d(xz), d(yz))(3) ground
      state in nonpolar solvents, such as toluene, benzene, and tetrachloromethane,
      because of the lack of hydrogen bonding in these solvents; (v) acetonitrile
      behaves like nonpolar solvents, such as toluene, benzene, and tetrachloromethane,
      though it is classified as a dipolar aprotic solvent. Although the NMR results
      have been interpreted in terms of the solvent effects on the ordering of the
      d(xy) and d(pi) orbitals, they could also be interpreted in terms of the solvent
      effects on the population ratios of two isomers with different electron
      configurations. In fact, we have observed the unprecedented EPR spectra at 4.2 K
      which contain both the axial- and large g(max)-type signals in some solvents such
      as benzene, toluene, and acetonitrile. The observation of the two types of
      signals has been ascribed to the slow interconversion on the EPR time scale at
      4.2 K between the ruffled complex with the (d(xz), d(yz))(4)(d(xy))(1) ground
      state and, possibly, the planar (or nearly planar) complex with the
      (d(xy))(2)(d(xz), d(yz))(3) ground state.

PMID- 12005503
TI  - Highly luminescent Eu(3+) and Tb(3+) macrocyclic complexes bearing an appended
      phenanthroline chromophore.
AB  - A two-component ligand system (1) containing 1,4,7,10-tetraazacyclododecane-1,4,7
      triacetic acid (DO3A) as the hosting unit for the lanthanide cations and an
      appended asymmetrically functionalized 1,10-phenanthroline (phen) as the
      chromophore was synthesized. The 1:1 complexes with Eu(3+), Gd(3+), Tb(3+), and
      Yb(3+) have been prepared and studied in aqueous solution. For Gd.1, a relaxivity
      value of 2.4 mM(-1) s(-1) has been measured at 20 MHz and 25 degrees C, which
      indicates that there are no water molecules in the first coordination sphere of
      the metal ion. The analysis of high resolution (1)H NMR spectra of Yb.1 supports
      this view and suggests the direct involvement of the phen moiety in the
      coordination of the metal ion. For Eu.1 and Tb.1, the absorption and luminescence
      spectra, the overall luminescence efficiencies, and the metal-centered (MC)
      lifetimes were obtained; coordination features were also determined by comparing
      luminescence properties in water and deuterated water. For Eu.1 and Tb.1, the
      overall emission sensitization (se) process in air-equilibrated water was found
      to be notably effective with phi(se) = 0.21 and 0.11, respectively. A detailed
      study of the steps originating from light absorption at the phen unit and leading
      to MC sensitized emission was performed.

PMID- 12005502
TI  - Oxidations of hydrocarbons by manganese(III) tris(hexafluoroacetylacetonate).
AB  - Mn(hfacac)(3) is an easily prepared and reactive oxidant (hfacac =
      hexafluoroacetylacetonate). It forms stable solutions in benzene and methylene
      chloride but is rapidly reduced in acetonitrile, DMSO, acetone, and ethers. It is
      reduced by ferrocene to give the Mn(II) complex [Cp(2)Fe][Mn(hfacac)(3)], which
      has been structurally characterized. Mn(hfacac)(3) also rapidly oxidizes 1
      acetylferrocene, 1,1'-diacetylferrocene, and tris(4-bromophenyl)amine. Based on
      an equilibrium established with tris(2,4-dibromophenyl)amine, a redox potential
      of 0.9 +/- 0.1 V vs Cp(2)Fe(+/0) is calculated. Mn(hfacac)(3) oxidizes 9,10
      dihydroanthracene (DHA) cleanly to anthracene, with a bimolecular rate constant
      of 6.8 x 10(-4) M(-1) s(-1) at 25 degrees C in benzene solution. In the presence
      of small amounts of water, the manganese(II) product is isolated as cis
      Mn(hfacac)(2)(H(2)O)(2), which has also been structurally characterized.
      Mn(hfacac)(3) also oxidizes xanthene to 9,9'-bixanthene, 1,4-cyclohexadiene to
      benzene, and 2,4-di-tert-butylphenol to the phenol dimer. Toluene and substituted
      toluenes are oxidized to tolylphenylmethanes. Product analyses and relative rates
      -for instance that p-methoxytoluene reacts much faster than toluene--indicate
      that the more electron rich substrates react by initial electron transfer to
      manganese. For the less electron rich substrates, such as 1,4-cyclohexadiene, a
      mechanism of initial hydrogen atom transfer to Mn(hfacac)(3) is suggested. The
      ability of Mn(hfacac)(3) to abstract H* is reasonable given its high redox
      potential and the basicity of [Mn(hfacac)(3)](-). In CH(2)Cl(2) solution,
      oxidation of DHA is catalyzed by chloride ion.

PMID- 12005504
TI  - Coordination chemistry and reactivity of monomeric alkoxides and amides of
      magnesium and zinc supported by the diiminato ligand CH(CMeNC(6)H(3)-2,6
      (i)Pr(2))(2). A comparative study.
AB  - The preparation and characterization of a series of closely related magnesium and
      zinc compounds are reported: LMg(N(i)Pr(2))(THF), 1; LZn(N(i)Pr(2)), 2;
      LMg(O(t)Bu)(THF), 3; LZn(O(t)Bu), 4; and LZn(OSiPh(3))(THF), 6; where L =
      CH(CMeNC(6)H(3)-2,6-(i)Pr(2))(2). Their dynamic solution behavior has been
      examined by variable-temperature NMR studies and reveals that THF reversibly
      dissociates in toluene-d(8) or CD(2)Cl(2) and that exchange with free THF occurs
      by a dissociative process. Compounds 1-4 and 6 all initiate and subsequently
      sustain ring-opening polymerization (ROP) of lactides. For a related series of
      compounds LMX(THF)(n)(), where n = 1 or 0, the rate of initial ring-opening
      follows the order M = Mg > Zn and X = O(t)Bu > N(i)Pr(2) > NSi(2)Me(6) >
      OSiPh(3). In THF at 25 degrees C, compounds 3 and 4 polymerize 100 equiv of rac
      lactide to >95% conversion in 5 and 80 min for M = Mg and Zn, respectively, and
      yield ca. 90% heterotactic PLA, (isi + sis tetrads). The reactions proceed faster
      in methylene chloride, but for M = Mg, a Bernoulian distribution of tetrads is
      formed from rac-lactide (3iii:2isi:sii:sis:iis) prior to trans-esterification.
      Polymerization of L-LA in toluene-d(8) and THF-d(8) by 3 and 4 have been studied
      by VT (1)H NMR spectroscopy: the resting state for zinc is proposed to be a
      monomeric species akin to LZn(eta(2)-OCHMeC(O)OMe), whereas the magnesium complex
      appears to be dimeric LMg(mu-OP)(2)MgL. None of the compounds is capable of
      initiating homopolymerization of propylene oxide (PO) or cyclohexene oxide (CHO),
      although the magnesium amide 1 effects ring-opening by allylic proton abstraction
      and the dimeric compound [LMg(mu-OC(6)H(9))](2), 7, is formed. Reactions with
      carbon dioxide are also described, along with the characterization of
      LZnO(2)CN(i)Pr(2), 8, which is shown to be inert with respect to CHO and PO at
      room temperature. All the compounds are hydrolytically sensitive, and LZn(mu
      OH)(2)ZnL, 5, has been isolated from hydrolysis of compound 4. The crystal and
      molecular structures are reported for compounds 1-5, 7, and 8. These results are
      compared with those recently reported by Coates et al.

PMID- 12005505
TI  - Ab initio structure of the (Na(2)[CAl(4)])(2) dimer. Next step toward solid
      materials containing tetracoordinate planar carbon.
AB  - We performed ab initio calculations on the (Na(2)[CAl(4)])(2) dimer in order to
      test if the two CAl(4)(2-) groups react to form the more stable dimeric
      structure, or if the two CAl(4)(2-) groups remain separated in a true dimeric
      structure. Working at the B3LYP/6-311+G* level of theory (previously found to be
      satisfactory in our earlier calculations with CAl(4)(-) and Na[CAl(4)](-)), we
      established that structures with the C-C bond are higher in energy than the
      structures with two isolated structural CAl(4)(-) units separated by more than 5
      A with their structural and electronic integrity preserved. However, alternative
      structures involving reaction between two CAl(4)(2-) groups forming a C(2)Al(8)(4
      ) cluster without the C-C bond are higher in energy, but they are still
      competitive with the true dimeric structure. While we found alternative
      structures of Na(4)C(2)Al(8) with the energy comparable to that of the true
      dimeric structure, we hope that the solid ionic salt with the pentaatomic
      tetracoordinate planar carbon [CAl(4)](2)(-) building block can be synthesized.

PMID- 12005506
TI  - Synthesis and characterization of uranyl compounds with iminodiacetate and
      oxydiacetate displaying variable denticity.
AB  - Eight uranyl compounds containing the dicarboxylate ligands iminodiacetate (IDA)
      or oxydiacetate (ODA) have been characterized in the solid state. The published
      polymeric structures for [UO(2)(C(4)H(6)NO(4))(2)] and [UO(2)(C(4)H(4)O(5))](n)
      have been confirmed, while Ba[UO(2)(C(4)H(5)NO(4))(2)] x 3H(2)O,
      [(CH(3))(2)NH(CH(2))(2)NH(CH(3))(2)][UO(2)(C(4)H(4)O(5))(2)] [orthorhombic space
      group Pnma, a = 10.996(5) A, b = 21.42(1) A, c = 8.700(3) A, Z = 4], and
      [C(2)H(5)NH(2)(CH(2))(2)NH(2)C(2)H(5)][UO(2)(C(4)H(4)O(5))(2)] [monoclinic space
      group P2(1)/n, a = 6.857(3) A, b = 9.209(5) A, c = 16.410(7) A, beta = 91.69(3),
      Z = 2] contain monomeric anions. The distance from the uranium atom to the
      central heteroatom (O or N) in the ligand varies. Crystallographic study shows
      that U-heteroatom (O/N) distances fall into two groups, one 2.6-2.7 A in length
      and one 3.1-3.2 A, the latter implying no bonding interaction. By contrast, EXAFS
      analysis of bulk samples suggests that either a long U-heteroatom (O/N) distance
      (2.9 A) or a range of distances may be present. Three possible structural types,
      two symmetric and one asymmetric, are identified on the basis of these results
      and on solid-state (13)C NMR spectroscopy. The two ligands in the complex can be
      1,4,7-tridentate, giving five-membered rings, or 1,7-bidentate, to form an eight
      membered ring. (C(4)H(12)N(2))[(UO(2))(2)(C(4)H(5)NO(4))(2)(OH)(2)] x 8H(2)O
      [monoclinic space group P2(1)/a, a = 7.955(9) A, b = 24.050(8) A, c = 8.223(6) A,
      beta = 112.24(6), Z = 2], (C(2)H(10)N(2))[(UO(2))(2)(C(4)H(5)NO(4))(2)(OH)(2)] x
      4H(2)O, and (C(6)H(13)N(4))(2)[(UO(2))(2)(C(4)H(4)O(5))(2)(OH)(2)] x 2H(2)O
      [monoclinic space group C2/m, a = 19.024(9) A, b = 7.462(4) A, c = 2.467(6) A,
      beta = 107.75(4), Z = 4] have a dimeric structure with two capping tridentate
      ligands and two mu(2)-hydroxo bridges, giving edge-sharing pentagonal bipyramids.

PMID- 12005507
TI  - Thermally reversible hydration of beta-chitin.
AB  - Thermally induced transition between anhydrous and hydrated forms of highly
      crystalline beta-chitin was studied by differential thermal calorimetry (DSC) and
      X-ray diffraction. DSC of wet beta-chitin in a sealed pan gave two well-defined
      endothermic peaks at 85.2 and 104.7 degrees C on heating and one broad exothermic
      peak at between 60 and 0 degrees C on cooling. These peaks were highly
      reproducible and became more distinct after repeated heating-cooling cycles. The
      X-ray diffraction pattern of wet beta-chitin at elevated temperature showed
      corresponding changes in d-spacing between the sheets formed by stacking of
      chitin molecules. These phenomena clearly show that water is reversibly
      incorporated into the beta-chitin crystal and that the temperature change induces
      transitions between anhydrous, monohydrate, and dihydrate forms. The DSC behavior
      in heating-cooling cycles, including reversion between the two endothermic peaks,
      indicated that the transition between monohydrate and dihydrate was a fast and
      narrow-temperature process, whereas the one between the anhydrous and the
      monohydrate form was a slow and wide-temperature process.

PMID- 12005508
TI  - A quartz crystal microbalance method for rapid detection and differentiation of
      shiga toxins by applying a monoalkyl globobioside as the toxin ligand.
AB  - A simple globobiosyl (Gb2) ceramide mimic carrying a monoalkyl chain (C18) was
      applied for a monolayer Langmuir-Blodgett (L-B) technique to detect Shiga toxins
      (Stxs) by a quartz crystal microbalance (QCM) method. The artificial glycolipid,
      synthesized from penta-O-acetyl-D-galactopyranose via a conventional
      glycosidation pathway, was developed at the air-water surface for the formation
      of the monolayer film. Then, the film was transferred onto a QCM cell surface
      modified with alkanethiols. Upon the addition of each of Stx-1 and Stx-2, the
      decrease of frequency reached saturation within 45 min at a few nanogram order
      per quartz cell. Binding constants (Ka) estimated for each of Stx-1 and Stx-2
      showed little difference between the two toxins. On the other hand, in the
      presence of an artificial acrylamido Gb2 copolymer as a competitive inhibitor,
      the two toxins showed a large difference in the binding behavior to the L-B
      monolayer.

PMID- 12005509
TI  - Microcalorimetric study of iodized and noniodized cells and C-phycocyanin of
      Spirulina platensis.
AB  - It was shown that eight stages of transition are observed in the heating process
      of Spirulina platensis cells in temperature range 5-140 degrees C. The first
      stage covers the temperature range 5-53 degrees C with maximum approximately 45
      degrees C. The heat evolved in this temperature range is equal to 380 +/- 20 J/g
      of dry biomass, it does not change at scanning rate lower than 0.083 degrees
      C/min and belongs, mainly, to cell respiration in a stationary regime, in the
      dark. It was shown that endotherm approximately 66 degrees C belongs to
      denaturation of C-phycocyanin which denaturates in solutions with Td = 64.2
      degrees C, deltaHd = 34.7 +/- 2.1 J/g and for it deltaHd(cal)/deltaH(V.H) is
      equal to 10.8 +/- 1.2. The endotherms with Td equal to 58 and 88 degrees C are
      connected with denaturation of phycobilisome proteins and endotherm with Td = 48
      degrees C and deltaHd = 4.2J/g of dry biomass-with denaturation of protein which,
      apparently, is connected with cell respiration.

PMID- 12005510
TI  - Presentation of epitopes on genetically engineered peptides and selection of
      lymphoma-targeting moieties based on epitope biorecognition.
AB  - A His-tagged coiled coil stem loop peptide with stable secondary structure was
      designed and biosynthesized. A series of oligopeptides related to the EBV
      envelope glycoprotein 350/220 N-terminal nonapeptide as potential CD21 receptor
      binding epitopes were engineered into the loop region of the peptide scaffold. It
      was shown that these peptides had a stable alpha-helical coiled coil structure
      and assumed a monomeric form in PBS. Biorecognition of the epitopes was studied
      by immobilizing the epitope-containing peptides on complexed Ni2+-containing
      surfaces through His-Ni2+ chelation and incubating with purified soluble CD21
      receptor or CD21+ cells. The results showed that the potential epitopes bound to
      CD21 and CD21+ cells at different affinities depending on oligopeptide
      structures. This approach allows for the evaluation of epitope
      biorecognizabilities and the selection of optimal oligopeptides among sequences
      for use as targeting moieties in the design of new lymphoma-targeting polymeric
      drug carriers.

PMID- 12005511
TI  - Immobilization of adenosine deaminase onto agarose and casein.
AB  - In the present study adenosine deaminase (ADA) was immobilized onto two different
      polymeric materials, agarose and casein. The factors affecting the amount of
      enzyme attachment onto the polymeric supports such as incubation time were
      investigated. The maximum amount of enzyme immobilized onto different polymeric
      supports occurred at incubation pH value 7.5 and ADA concentration 42 units/g and
      the incubation time needed for the maximum amount of enzyme attachment to the
      polymeric supports was found to be 8 h. Some phsicochemical properties of the
      free and immobilized ADA such as operational stability, optimum temperature and
      thermal stability, pH optimum and stability, storage stability, and the effect of
      gamma-radiation were studied. The operational stability of the free and
      immobilized enzyme showed that the enzyme immobilized by a cross-linking
      technique using gultaric dialdehyde showed poor durability and the relative
      activity decreased sharply due to the leakage after repeated washing, while the
      enzymes immobilized by covalent bonds to the carriers showed a slight decrease in
      most cases in the relative activity (around 20%) after being used 10 times.
      Storage for 4-6 months, showed that the free enzyme lost its activity, while the
      immobilized enzyme showed the opposite behavior. Subjecting the immobilized
      enzyme to a dose of gamma radiation of 0.5-10 Mrad showed complete loss in the
      activity of the free enzyme at a dose of 5 Mrad, while the immobilized enzymes
      showed relatively high resistance to gamma radiation up to a dose of 5 Mrad.

PMID- 12005512
TI  - Complex formation of cytochrome C with a calixarene carboxylic acid derivative: a
      novel solubilization method for biomolecules in organic media.
AB  - A calixarene carboxylic acid derivative has been found to form a complex with the
      cationic protein cytochrome c. The solubilized cytochrome c was stable and showed
      peroxidase activity in chloroform. The calix[6]arene and the calix[8]arene
      achieved quantitative extraction of the protein. The calix[6]arene, whose cavity
      is well-fitted to a protonated amino group, exhibited a selectivity to lysine
      rich proteins due to the recognition of the epsilon-amino groups in lysine
      residues on the surface of the protein. This is the first report showing protein
      extraction by calixarenes. The solubilized cytochrome c could catalyze an
      oxidative reaction in organic solvents. This host compound functions as a novel
      solubilization tool for biomolecules and a separation tool for lysine-rich
      proteins.

PMID- 12005514
TI  - Characterization and intermolecular interactions of hydroxypropyl guar solutions.
AB  - Aqueous solutions of guar galactomannan and hydroxypropyl guars (HPG) with
      different molar substitution (MS) levels were studied using dilute solution
      viscometry and gel permeation chromatography. When guar is modified to HPG, the
      added hydroxypropyl groups sterically block the hydrogen bonding sites on the
      guar backbone and reduce the hydrogen bonding attractions between guar molecules.
      The effects of molar substitution on the intermolecular interactions are inferred
      from measurements of the Huggins coefficients, which measure intermolecular
      interactions in dilute solution, and molecular volumes, which reflect intrachain
      associations. The behavior can be divided into three regimes: (1) at low MS
      levels (0 < MS < approximately 0.4), there is a sharp decrease in intermolecular
      interactions as a function of MS; (2) in the intermediate range ( approximately
      0.4 < MS < approximately 1.0), interactions become independent of MS; (3) at high
      substitution levels (MS > approximately 1.0), the temperature dependence of inter
      and intramolecular hydrophobic interactions produces a temperature dependence in
      the Huggins coefficient and molecular volumes that is not seen at lower
      substitutions. By acid hydrolysis, HPG samples with a range of molecular weights
      and consistent polydispersities were obtained. On the basis of these samples, the
      Mark-Houwink-Sakurada parameters and "characteristic ratio" C(infinity) were
      evaluated for HPG (MS approximately 0.6) and compared to the values for guar. The
      HPG chain stiffens as the degree of substitution increases.

PMID- 12005513
TI  - Biodegradation of lactic acid based polymers under controlled composting
      conditions and evaluation of the ecotoxicological impact.
AB  - The biodegradability of lactic acid based polymers was studied under controlled
      composting conditions (CEN prEN 14046), and the quality of the compost was
      evaluated. Poly(lactic acids), poly(ester-urethanes), and poly(ester-amide) were
      synthesized and the effects of different structure units were investigated. The
      ecotoxicological impact of compost samples was evaluated by biotests, i.e., by
      the Flash test, measuring the inhibition of light production of Vibrio fischeri,
      and by plant growth tests with cress, radish, and barley. All the polymers
      biodegraded to over 90% of the positive control in 6 months, which is the limit
      set by the CEN standard. Toxicity was detected in poly(ester-urethane) samples
      where chain linking of lactic acid oligomers had been carried out with 1,6
      hexamethylene diisocyanate (HMDI). Both the Flash test and the plant growth tests
      indicated equal response to initial HMDI concentration in the polymer. All other
      polymers, including poly(ester-urethane) chain linked with 1,4-butane
      diisocyanate, showed no toxicological effect.

PMID- 12005515
TI  - Heavy metal removal by novel CBD-EC20 sorbents immobilized on cellulose.
AB  - Heavy metals are major contributors to pollution of the biosphere, and their
      efficient removal from contaminated water is required. Biosorption is an emerging
      technology that has been shown to be effective in removing very low levels of
      heavy metal from wastewater. Although peptides such as metallothioneins or
      phytotchelatins are known to immobilize heavy metals, peptide-based biosorbents
      have not been extensively investigated. In this paper, we describe the
      construction and expression of bifunctional fusion proteins consisting of
      synthetic phytochelatin (EC20) linked to a Clostridium-derived cellulose-binding
      domain (CBD(clos)), enabling purification and immobilization of the fusions onto
      different cellulose materials in essentially a single step. The immobilized
      sorbents were shown to be highly effective in removing cadmium at parts per
      million levels. Repeated removal of cadmium was demonstrated in an immobilized
      column. The ability to genetically engineer biosorbents with precisely defined
      properties could provide an attractive strategy for developing high-affinity
      bioadsorbents suitable for heavy metal removal.

PMID- 12005516
TI  - Interpenetrating network formation in agarose--kappa-carrageenan gel composites.
AB  - Thermal, mechanical, turbidity, and microscope evidence is provided which
      strongly suggests molecular interpenetrating network (IPN) formation by mixtures
      of the seaweed polysaccharides agarose and kappa-carrageenan. Over a range of
      ionic strength, and potassium content, there is no evidence for synergistic
      coupling of the networks, and simple phase separation (demixing) can definitely
      be ruled out. At low ionic strength, where the agarose gels first, differential
      scanning calorimetry evidence shows some influence of the carrageenan on the
      agarose ordering enthalpy, particularly at higher polymer concentrations. As the
      potassium level is increased, however, and the order of gelling is reversed, this
      effect disappears. Cure behavior for the systems at high ionic strength can be
      described as a simple summation of the pure component contributions. At low ionic
      strength, on the other hand, the modulus behavior is more complex, suggesting
      either a modification, in the mixture, of the kappa-carrageenan gelling
      parameters or a more complex modulus additivity rule.

PMID- 12005517
TI  - Synthesis of chitosan-stabilized polymer dispersions, capsules, and chitosan
      grafting products via miniemulsion.
AB  - The potential of chitosan as an emulsion stabilizer is combined with the
      miniemulsion technique to generate oil droplets, hollow capsules, and latex
      particles in the diameter range of 100-300 nm carrying a functional biopolymer
      surface. It turned out that chitosan alone, independent of its molecular weight,
      is just moderately efficient, which is speculatively attributed to its stiff
      polysaccharide structure. The addition of biocompatible costabilizers with higher
      flexibility either to the oil phase or to the water phase, such as Jeffamine or
      Gluadin (a peptide), eliminates these deficiencies, and very small nanocapsules
      made of biopolymer hybrids can be obtained. NMR analysis shows that the
      costabilizer is effectively grafted/cross-linked to the chitosan which makes the
      miniemulsion route also effective for the modification of hard-to-handle,
      amphiphilic biopolymers either from the water or from the oil phase.

PMID- 12005518
TI  - Dynamic light scattering and circular dichroism studies on heat-induced gelation
      of hard-keratin protein aqueous solutions.
AB  - Animal hairs consist of aggregates of dead cells filled with keratin protein gel.
      We succeeded in preparing water-soluble hard-keratin proteins and reconstructing
      the keratin gels by heat-induced disulfide linkages in vitro. Here, the roles of
      intermolecular hydrophobic interaction and disulfide bonding between the proteins
      in the gel were discussed. Water-soluble keratin proteins consisting of mixtures
      of type I ( approximately 48 kDa) and type II ( approximately 61 kDa) were
      prepared from wool fibers as S-carboxymethyl alanyl disulfide keratin (CMADK).
      The gelation was achieved by heating an aqueous solution containing at least 0.8
      wt % CMADK at 100 degrees C. CMADK solutions with different urea or N
      ethylmaleimide concentrations or pH were exposed to dynamic light scattering
      (DLS) and circular dichroism (CD). DLS clarified the gelation point of CMADK
      solutions and provided information on the changes in keratin cluster size. DLS
      suggested two types of gelation mechanism. One was the regenerated chemical
      disulfide bonding between keratins from CMAD parts of chains. After the gel
      formed, this bond became important to maintain the gel structure. The other was
      the physical assembly due to hydrophobic interaction between alpha-helix parts of
      keratin chains. This hydrophobic assembly also played an important role during
      gelation. CD confirmed a conformational change in the keratin protein, resulting
      heat-induced gelation. CD clarified the relationship between keratin protein
      conformation and gelation, i.e., a rodlike conformation with many alpha-helix
      structures was necessary to associate keratin chains and form a gel network.

PMID- 12005519
TI  - Mechanism of heat and shear mediated aggregation of wheat gluten protein upon
      mixing.
AB  - Changes in wheat gluten network structure upon mixing were studied from the
      biochemical analyses of gluten/glycerol blends mixed at 100 rpm with increasing
      times (up to 30 min) and temperatures of regulation (40, 60, and 80 degrees C).
      Whereas mixing induced protein solubility loss, the reduction of disulfide bonds
      restored protein extractability. But disulfide bond reduction became less
      efficient in promoting gluten extractability as mixing severity increased. This
      feature is consistent with the formation of a three-dimensional protein network
      stabilized by the formation of an increasing number of interchain disulfide
      bonds. Mixing induced a transient increase in free thiol groups while total thiol
      equivalent groups dropped continuously. The changes were attributed to a shear
      mediated scission of gluten disulfide bonds followed by oxidation of the thiyl
      radical moieties. Upon mixing, gluten solubility loss showed an Arrhenius-type
      temperature dependence with activation energy of 33.7 kJ.mol-1 instead of the
      more than 100 kJ.mol-1 reported for heat-induced gluten protein solubility loss.
      To explain this discrepancy, we postulated that during mixing, the disulfide
      interchange reactions are mediated by thiyl radicals in place of free thiol
      groups. A general model accounting for shear and temperature effects on gluten
      network structure is proposed.

PMID- 12005520
TI  - Xanthan and glucomannan mixtures: synergistic interactions and gelation.
AB  - The synergistic interaction between xanthan and glucomannan in solution and in
      the gel phase has been studied by circular dichroism spectroscopy and
      differential scanning calorimetry. The study in solution of the polysaccharidic
      mixture indicates a preferred stoichiometry of the interaction corresponding to a
      weight fraction of xanthan around 0.55. This finding is in reasonable agreement
      with the differential scanning calorimetry measurements carried out on the gel
      phase. Models from conformational analysis based on these results were formulated
      in terms of 1:1 and 2:1 Konjac glucomannan/xanthan molecular assemblies. The
      experimental and calculation results clearly indicate the involvement of the side
      chains of xanthan and suggest that the ordered portions of the macromolecular
      complex in solution act in the gel phase as junction zones.

PMID- 12005521
TI  - Argon microwave plasma treatment and subsequent hydrosilylation grafting as a way
      to obtain silicone biomaterials with well-defined surface structures.
AB  - A method of grafting well-defined and hydrolytically stable surface structures
      onto cross-linked poly(dimethylsiloxane) (PDMS) has been developed. In the first
      step, argon microwave plasma was used to introduce Si-H groups onto the surface.
      In the second step, allyltetrafluoroethyl ether was grafted to these Si-H groups
      using a platinum-catalyzed hydrosilylation reaction. The influences of the plasma
      parameters of power, pressure, and treatment time on the surface composition,
      both before and after the hydrosilylation step, were investigated by X-ray
      photoelectron spectroscopy and contact angle measurements. It was found that the
      pressure had little influence on the results, whereas the power and treatment
      time determined the rate of change in surface composition during the plasma
      treatment. The graft yield reached a plateau value corresponding to about 5%
      grafted molecules in the analyzed surface region. Hydrosilylation grafting of
      PDMS is a promising method to obtain biomaterials with hydrolytically stable
      structures covalently bound to the surface.

PMID- 12005522
TI  - Sol-gel transition temperature of PLGA-g-PEG aqueous solutions.
AB  - Aqueous solutions of poly(DL-lactic acid-co-glycolic acid)-g-poly(ethylene
      glycol) copolymers exhibited sol-to-gel transition with increasing temperature.
      Further increase in temperature makes the system flow and form a sol phase again.
      Subcutaneous injection of a copolymer aqueous solution (0.5 mL) resulted in a
      formation of a hydrogel depot by temperature-sensitive sol-to-gel transition in a
      rat model. The reliable determination and control of sol-to-gel transition
      temperatures are the most important issues for this kind of sol-gel reversible
      hydrogel. The sol-to-gel transition temperature determined by the test tube
      inverting method, falling ball method, and dynamic mechanical analysis coincided
      within 1-2 degrees C. Fine tuning of the sol-to-gel transition temperature was
      achieved by varying the ionic strength of the polymer solutions and by mixing two
      polymer aqueous solutions with different sol-to-gel transition temperatures. The
      sol-to-gel transition temperature of polymer mixture aqueous solutions was well
      described by an empirical equation of miscible blends, indicating miscibility of
      the two polymer systems in water on the molecular level.

PMID- 12005523
TI  - Permeation of macromolecules into polyelectrolyte microcapsules.
AB  - Polyelectrolyte microcapsules (PEMCs) have been prepared by coating red blood
      cells with the polyelectrolytes poly(styrenesulfonate), poly(allylamine
      hydrochloride), and dextran sulfate applying the layer-by-layer technique with
      subsequent dissolution of the core. The capsule permeability for human serum
      albumin (HSA) was studied as a function of the ionic strength and pH by means of
      confocal microscopy. PEMCs produced with dextran sulfate and poly(allylamine
      hydrochloride) show a significant increase in permeability for HSA at salt
      concentrations over 1 mM. For PEMCs prepared with poly(styrenesulfonate) and
      poly(allylamine hydrochloride) the limiting salt concentration is 5 mM. No pH
      dependence for permeation was observed. A correlation between the permeation and
      adsorption of HSA on the PEMC walls was investigated. Finally, a mechanism for
      the permeability, combining electrostatic interactions, and the presence of pores
      in the polymer layers is presented confirmed by the considerable increase of
      permeation of charged molecules in the presence of salt and the permeation of
      neutral molecules regardless of the ionic strength.

PMID- 12005524
TI  - Enzymatic degradation of block copolymers prepared from epsilon-caprolactone and
      poly(ethylene glycol).
AB  - Block copolymers were prepared by ring-opening polymerization of epsilon
      caprolactone in the presence of monohydroxyl or dihydroxyl poly(ethylene glycol)
      (PEG), using Zn powder as catalyst. The resulting poly(epsilon-caprolactone)
      (PCL)-PEG diblock and PCL-PEG-PCL triblock copolymers were characterized by
      various analytical techniques such as NMR, size-exclusion chromatography,
      differential scanning calorimetry, and X-ray diffraction. Both copolymers were
      semicrystalline polymers, the crystalline structure being of the PCL type. Films
      were prepared by casting dichloromethane solutions of the polymers on a glass
      plate. Square samples with dimensions of 10 x 10 mm were allowed to degrade in a
      pH = 7.0 phosphate buffer solution containing Pseudomonas lipase. Data showed
      that the introduction of PEG blocks did not decrease the degradation rate of
      poly(epsilon-caprolactone).

PMID- 12005525
TI  - Molecular mobility of elastin: effect of molecular architecture.
AB  - The thermal and dielectric properties of elastin and two soluble derivatives
      (kappa-elastin and derived elastin peptides from enzymatic elastolysis) were
      investigated in the freeze-dried state in a wide temperature range (from -180 to
      +220 degrees C). The glass transition of these amorphous proteins was studied by
      differential scanning calorimetry (DSC). The dielectric relaxations of both
      proteins were followed by thermally stimulated currents (TSC), an isochronal
      dielectric spectrometry running at variable temperature, analogous to a low
      frequency spectroscopy (10(-3)-10(-2) Hz) and by dynamic dielectric spectroscopy
      (DDS), performed isothermally with the frequency varying from 10(-2) to 3 x 10(6)
      Hz. The combination of TSC and DDS experiments and the determination of the
      activation parameters of the relaxation times inform about the molecular mobility
      of the proteins, both in the glassy state and in the liquid state. Major
      differences between the relaxation behavior of elastin and its soluble
      derivatives have been discussed and correlated with the molecular architecture of
      the proteins.

PMID- 12005526
TI  - The utility of a 3-O-allyl group as a protective group for ring-opening
      polymerization of alpha-D-glucopyranose 1,2,4-orthopivalate derivatives.
AB  - To clarify the utility as a protective group of 3-O-allyl group on ring-opening
      polymerization of alpha-D-glucopyranose 1,2,4-orthopivalate derivatives, four
      orthopivalate derivatives, 3-O-allyl-6-O-pivaloyl- (1), 3-O-allyl-6-O-benzyl-
      (2), 3,6-di-O-allyl- (3), and 3-O-allyl-6-O-methyl-alpha-D-glucopyranose 1,2,4
      orthopivalates (4), were selected as starting monomers and were polymerized under
      -30 degrees C in CH2Cl2 using BF3.Et2O as a catalyst. All the orthopivalate
      derivatives 1-4 were found to give stereoregular polysaccharides, (1-->4)-beta-D
      glucopyranans. Thus, it was concluded that the allyl group as a protective group
      at 3-O position of glucose othropivalate is acceptable to yield stereoregular (1-
      >4)-beta-D-glucopyranans, cellulose derivatives.

PMID- 12005527
TI  - Biological properties of hyaluronan in aqueous solution are controlled and
      sequestered by reversible tertiary structures, defined by NMR spectroscopy.
AB  - Hyaluronan (HA) is a ubiquitous polysaccharide of (predominantly) animal origin
      that has important medical applications in joint, skin, and eye conditions.
      Biological activities shown by HA fragments in angiogenesis, inflammation, etc.
      are absent from highly polymerized HA. We propose that HA physiological
      properties are controlled by molecular mass dependent transitions between
      tertiary structures (e.g., beta sheets) and 2-fold helices, - reversible
      "denaturation", which is central to HA solution behavior. We demonstrate this
      phenomenon by 13C NMR. Four different acetamido C=O resonances, assigned to
      secondary, tertiary, and disordered HA structures, monitored "denaturation" by
      (a) warming, (b) alkalinizing to pH >12.0, (c) hyaluronidase digestion, and (d)
      methylation of carboxylates. (a) and (b) acted reversibly but (c) and (d) are
      irreversible. 1H NMR implicated H-bonded acetamido NH in (b). Temperature
      dependencies of other 13C chemical shifts were small and unspecific. Arrhenius
      plots indicate that hyaluronan tertiary structures are on the edge of instability
      under physiological conditions. The results help to explain the appearance of
      biological activities on "denaturation" or degradation of HA.

PMID- 12005528
TI  - PFG-NMR measurements of the self-diffusion coefficients of water in equilibrium
      poly(HEMA-co-THFMA) hydrogels.
AB  - The self-diffusion coefficients for water in a series of copolymers of 2
      hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA,
      swollen with water to their equilibrium states have been studied at 310 K using
      PFG-NMR. The self-diffusion coefficients calculated from the Stejskal-Tanner
      equation, D(obs), for all of the hydrated polymers were found to be dependent on
      the NMR storage time, as a result of spin exchange between the proton reservoirs
      of the water and the polymers, reaching an equilibrium plateau value at long
      storage times. The true values of the diffusion coefficients were calculated from
      the values of D(obs) in the plateau regions by applying a correction for the
      fraction of water protons present, obtained from the equilibrium water contents
      of the gels. The true self-diffusion coefficient for water in polyHEMA obtained
      at 310 K by this method was 5.5 x 10(-10) m(2)s-1. For the copolymers containing
      20% HEMA or more a single value of the self-diffusion coefficient was found,
      which was somewhat larger than the corresponding values obtained for the
      macroscopic diffusion coefficient from sorption measurements. For polyTHFMA and
      copolymers containing less than 20% HEMA, the PFG-NMR stimulated echo attenuation
      decay curves and the log-attenuation plots were characteristic of the presence of
      two diffusing water species. The self-diffusion coefficients of water in the
      equilibrium-hydrated copolymers were found to be dependent on the copolymer
      composition, decreasing with increasing THFMA content.

PMID- 12005529
TI  - Electrostatic layer-by-layer nanoassembly on biological microtemplates:
      platelets.
AB  - Platelets were coated with 78-nm silica nanoparticles, 45-nm fluorescent
      nanospheres, or bovine immunoglobulin G (IgG) through layer-by-layer assembly by
      alternate adsorption with oppositely charged linear polyions. Sequential
      deposition on platelet surfaces of cationic poly(dimethyldiallylammonium
      chloride) and anionic poly(styrene sulfonate) was followed by adsorption of
      nanoparticles or immunoglobulins. Nano-organized shells of platelets were
      demonstrated by transmission electron microscopy and fluorescence microscope
      images. Bovine IgG was assembled on platelets, as verified with anti-bovine IgG
      FITC labeling. Localized targeting of anti-IgG shelled platelets was also
      demonstrated. An ability to coat blood cells with nano-organized shells can have
      applications in cardiovascular research and targeted drug delivery.

PMID- 12005530
TI  - Structure of artificial cytoskeleton containing liposomes in aqueous solution
      studied by static and dynamic light scattering.
AB  - The structure of three types of liposomes (egg yolk phosphatidylcholine (EPC)
      without modification and EPC vesicles containing cross-linked N
      isopropylacrylamide (NIPAM) networks of low and a high concentration inside the
      vesicles) were analyzed by static and dynamic light scattering. Upon
      polymerization the network was assumed to become attached to the membrane by
      reactive anchoring monomers. For the sample of high poly(NIPAM) content the
      polymer network was assumed to fill the whole space in the vesicles. The issue of
      the present study was to examine hard and hollow sphere behavior of the liposomes
      with networks of high and low poly(NIPAM) content. The theoretical scattering
      curves differ markedly for uniform hard and uniform hollow spheres by the
      presence of specific peaks. However, polydispersity washed out the peaks and led
      to smoothed asymptotes with fractal dimensions of df = 2 for hollow and df = 4
      for hard spheres. The experimental data could efficiently be fitted with weakly
      polydisperse hollow spheres. No clear conclusion could be drawn from the angular
      dependence alone for the liposome of high poly(NIPAM) content. The two
      wavelengths from the HeNe and Ar lasers proved to be too long for the studied
      liposomes of about 100 nm in radius. However, evidence for hollow sphere behavior
      was found for fractionated liposomes from the ratio rho = Rg/Rh = 1.04 +/- 0.02
      (theory rho = 1.00 for hollow spheres). Finally, from the molar mass and the
      sphere radius, an apparent density was determined. The analysis gave the expected
      density for the pure EPC lecithin vesicles and a poly(NIPAM) network density of
      0.244 g/mL. For the liposome of low poly(NIPAM) content the network appeared to
      be attached to the inner surface of the lecithin shell to form a layer of about
      18 nm thickness.

PMID- 12005531
TI  - Polyelectrolyte complexes and layer-by-layer capsules from chitosan/chitosan
      sulfate.
AB  - Polyelectrolyte complex formation of chitosans of varying average molecular
      weight and degree of acetylation with chitosan sulfate or poly(styrene sulfonate)
      was studied by static light scattering in dilute solution at various ionic
      strengths. Unlike the molecular weight, the degree of acetylation was found to
      have a significant effect on the resultant structural densities of the complexes.
      The same system was applied to the preparation of micrometer-sized hollow shells
      by means of a layer-by-layer technique (in total eight layers). Their behavior
      toward fluorescent probes such as fluorescein and rhodamin 6G or fluorescein
      isothiocyanate labeled dextrans at various ionic strengths and pH (observed by
      confocal laser light scanning microscopy) could be understood through a
      discussion of electrostatic forces between the highly charged shells and the
      probes to be dominant. At an ionic strength of 0.1 M and above, charge effects
      are largely suppressed (screening effect) and a size-dependent "cutoff" for the
      permeation of the macromolecular fluorophore was observed.

PMID- 12005532
TI  - Poly(N-isopropylacrylamide)-based semi-interpenetrating polymer networks for
      tissue engineering applications. 1. Effects of linear poly(acrylic acid) chains
      on phase behavior.
AB  - Poly(N-isopropylacrylamide)-based [P(NIPAAm)-based] semi-interpenetrating polymer
      networks (semi-IPNs), consisting of P(NIPAAm)-based hydrogels and linear
      poly(acrylic acid) [P(AAc)] chains, were synthesized, and the effects of the
      P(AAc) chains on semi-IPN injectability and phase behavior were analyzed. In
      P(NIPAAm)- and P(NIPAAm-co-AAc)-based semi-IPN studies, numerous reaction
      conditions were varied, and the effects of these factors on semi-IPN
      injectability, transparency, phase transition, lower critical solution
      temperature (LCST), and volume change were examined. The P(AAc) chains did not
      significantly affect the LCST or volume change of the semi-IPNs, compared to
      control hydrogels. However, the P(AAc) chains affected the injectability,
      transparency, and phase transition of the matrices, and these effects were
      dependent on chain amount and molecular weight (MW) and on interactions between
      the P(AAc) chains and the solvent and/or copolymer chains in P(NIPAAm-co-AAc)
      hydrogels. These results can be used to design "tailored" P(NIPAAm)-based semi
      IPNs that have the potential to serve as functional scaffolds in tissue
      engineering applications.

PMID- 12005533
TI  - Resorbable and highly elastic block copolymers from 1,5-dioxepan-2-one and L
      lactide with controlled tensile properties and hydrophilicity.
AB  - New resorbable and elastomeric ABA tri- and multiblock copolymers have been
      successfully synthesized by combining ring-opening polymerization with ring
      opening polycondensation. Five different poly(L-lactide-b-1,5-dioxepan-2-one-b-L
      lactide) triblock copolymers and one new poly(L-lactide-b-1,5-dioxepan-2-one)
      multiblock copolymer have been synthesized. The triblock copolymers were obtained
      by ring-opening polymerization of 1,5-dioxepan-2-one (DXO) and L-lactide (LLA)
      with a cyclic tin initiator. The new multiblock copolymer was prepared by ring
      opening polycondensation of a low molecular weight triblock copolymer with
      succinyl chloride. The molecular weight and the composition of the final
      copolymers were easily controlled by adjusting the monomer feed ratio, and all of
      the polymers obtained had a narrow molecular weight distribution. It was possible
      to tailor the hydrophilicity of the materials by changing the DXO content.
      Copolymers with a high DXO content had a more hydrophilic surface than those with
      a low DXO content. The receding contact angle varied from 27 to 44 degrees. The
      tensile properties of the copolymers were controlled by altering the PDXO block
      length. The tensile testing showed that all the polymers were very elastic and
      had very high elongations-at-break (epsilon(b)). The copolymers retained very
      good mechanical properties (epsilon(b) approximately 600-800% and sigma(b)
      approximately 8-20 MPa) throughout the in vitro degradation study (59 days).

PMID- 12005534
TI  - Morphological investigation of nanocomposites from sorbitol plasticized starch
      and tunicin whiskers.
AB  - Nanocomposites were prepared from waxy maize starch plasticized with sorbitol as
      the matrix and a stable aqueous suspension of tunicin whiskers-an animal
      cellulose-as the reinforcing phase. The composites were conditioned at different
      relative humidity levels. The conditioned films were characterized using scanning
      electron microscopy, differential scanning calorimetry, water uptake experiments,
      and wide-angle X-ray scattering studies. Contrarily to our previous report
      concerning tunicin whisker filled glycerol plasticized starch nanocomposites
      (Macromolecules 2000, 33, 8344), the present system exhibited a single glass
      rubber transition, and no evidence of transcrystallization of amylopectin on
      cellulose whisker surfaces and resultant antiplasticizing effects were observed.
      It was found that the glass-rubber transition temperature of the plasticized
      amylopectin matrix first increases up a whiskers content around 10-15 wt % and
      then decreases. A significant increase in crystallinity was observed in the
      composites by increasing either moisture content or whiskers content.

PMID- 12005535
TI  - Engineering of Ralstonia eutropha for production of poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) from fructose and solid-state properties of the copolymer.
AB  - Recombinant Ralstonia eutropha capable of producing poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) copolymer [P(3HB-co-3HHx)] from fructose was engineered by
      introduction of genes for crotonyl-CoA reductase (CCR) from Streptomyces
      cinnamonensis (ccrSc) and for PHA synthase and (R)-specific enoyl-CoA hydratase
      from Aeromonas caviae (phaC-JAc). In this recombinant strain, C6-acyl-CoA
      intermediates were provided via beta-ketothiolase-mediated elongation of butyryl
      CoA, which was generated from crotonyl-CoA by the function of CCR. The
      recombinant strain could accumulate the copolyester up to 48 wt % of dry cell
      weight with 1.5 mol % of 3HHx fraction from fructose, when the expression of
      ccrSc under the control of the PBAD promoter was induced with 0.01% L-arabinose.
      The absence of L-arabinose or the deletion of ccrSc from the plasmid resulted in
      accumulation of poly(3-hydroxybutyrate) homopolymer, indicating the critical role
      of CCR in the formation of the 3-hydroxyhexanoate unit. Higher CCR activity
      obtained by the addition of a larger amount of L-arabinose did not affect the
      composition but reduced the intracellular content of the copolyester. The P(3HB
      co-1.5 mol % 3HHx) copolyester produced from fructose by the recombinant R.
      eutropha showed relatively lower melting temperatures (150 degrees C and 161
      degrees C) and lower crystallinity (48 +/- 5%) compared to those (175 degrees C
      and 60 +/- 5%) of P(3HB) homopolymer. It has been found that the incorporation of
      a small amount (1.5 mol %) of 3HHx units into P(3HB) sequences leads to a
      remarkable change in the solid-state properties of P(3HB) crystals. The present
      study demonstrates the potential of the engineered pathway for the production of
      copolyesters having favorable characteristics from inexpensive carbon resources.

PMID- 12005536
TI  - Coimmobilization of gluconolactonase with glucose oxidase for improvement in
      kinetic property of enzymatically induced volume collapse in ionic gels.
AB  - The object of this paper is to provide an enzymatic means to attain faster
      swelling or shrinking kinetics of polyelectrolyte gels that undergo volume phase
      transition as an immobilized enzyme reaction sets in. For this, we studied the
      coimmobilization of gluconolactonase (GL) with glucose oxidase (GOD). A gel used
      was in the shape of a small cylinder (several hundred micrometers in diameter)
      and composed of a lightly cross-linked copolymer of N-isopropylacrylamide and
      acrylic acid. GL was isolated from Aspergillus niger and purified about 100-fold.
      It was found that in a substrate solution containing glucose, the gel with the
      coimmobilized GL and GOD shrinks very rapidly. The shrinking rate was identical
      to that of the enzyme-free gel that undergoes a shrinking transition in response
      to a sudden pH change of the outer medium from 7 to 5. This indicates the rate
      limiting step in the shrinking process to be diffusion of the networks, but not
      the enzyme reaction. In the gel with singly immobilized GOD, a very slow
      shrinking was observed because the process is governed by the enzyme reaction.
      These results were discussed in full in connection with an enzymatically induced
      decrease in pH within and in the vicinity of the gel phase. As a result, it has
      become apparent that the faster shrinking kinetics in the coimmobilized enzyme
      system is attained by the GL-catalyzed hydrolysis of D-glucono-delta-lactone
      resulting from the oxidation of glucose with GOD.

PMID- 12005537
TI  - Electrosorption of pectin onto casein micelles.
AB  - Pectin, a polysaccharide derived from plant cells of fruit, is commonly used as
      stabilizer in acidified milk drinks. To gain a better understanding of the way
      that pectin stabilizes these drinks, we studied the adsorption and layer
      thickness of pectin on casein micelles in skim milk dispersions. Dynamic light
      scattering was used to measure the layer thickness of adsorbed pectin onto casein
      micelles in situ during acidification. The results indicate that the adsorption
      of pectin onto casein micelles is multilayered and takes place at and below pH
      5.0. Renneting, i.e., cleaving-off kappa-casein from the casein micelles, did not
      alter the adsorption pH. It did, however, show that pectin arrests the rennet
      induced flocculation of casein micelles below pH 5.0. From the findings we
      concluded the attachment of pectin onto casein micelles is driven by
      electrosorption. Adsorption measurements confirmed the multilayered nature of the
      adsorption of pectin onto casein micelles. Both the adsorbed amount and the layer
      thickness increased with decreasing pH in the relevant range 3.5-5.0. The phase
      behavior of a casein micelles/pectin mixture was determined and could be
      explained in terms of thermodynamic incompatibility being relevant above pH 5.0
      and adsorption, leading to either stabilization and bridging, being relevant
      below pH 5.0. The results confirm that electrosorption is the driving force for
      the adsorption of pectin onto casein micelles.

PMID- 12005538
TI  - Clustered DNA damages induced by x rays in human cells.
AB  - Although DNA DSBs are known to be important in producing the damaging effects of
      ionizing radiation in cells, bistranded clustered DNA damages-two or more
      oxidized bases, abasic sites or strand breaks on opposing DNA strands within a
      few helical turns-are postulated to be difficult to repair and thus to be
      critical radiation-induced lesions. Gamma rays can induce clustered damages in
      DNA in solution, and high-energy iron ions produce DSBs and oxidized pyrimidine
      clusters in human cells, but it was not known whether sparsely ionizing radiation
      can produce clustered damages in mammalian cells. We show here that X rays induce
      abasic clusters, oxidized pyrimidine clusters, and oxidized purine clusters in
      DNA in human cells. Non-DSB clustered damages comprise about 70% of the complex
      lesions produced in cells. The relative levels of specific cluster classes depend
      on the environment of the DNA.

PMID- 12005539
TI  - Dose-response curves and tolerance doses for late functional changes in the
      normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance
      imaging: influence of end points and follow-up time.
AB  - Late reaction of normal tissue is still a limiting factor in radiotherapy and
      radiosurgery of patients with brain tumors. Few quantitative data in terms of
      dose-response curves are available. In the present study, 99 animals were
      irradiated stereotactically at the right frontal lobe using a linear accelerator
      and single doses between 26 and 50 Gy. The diameter of the spherical dose
      distribution was 4.7 mm (80% isodose). Dose-response curves for late changes in
      the normal brain at 20 months were measured using T1- and T2-weighted magnetic
      resonance imaging (MRI). The dependence of the dose-response curves on the follow
      up time and the definition of the biological end point were determined. Tolerance
      doses were calculated at several effect probability levels and times after
      irradiation. The MRI changes were found to be dependent on dose and progressive
      in time. At 20 months, the tolerance doses at a 50% effect probability level were
      39.6 +/- 1.0 Gy and 42.4 +/- 1.4 Gy for changes in T1- and T2-weighted images,
      respectively. These dose-response curves can be used for further quantitative
      investigations on the influence of various treatment parameters, such as the
      application of charged particles, radiopharmaceuticals or the variation of tissue
      oxygenation.

PMID- 12005540
TI  - Quantitative analysis of varying profiles of hypoxia in relation to functional
      vessels in different human glioma xenograft lines.
AB  - Tissue oxygenation influences the radiation response of tumors. To further
      investigate the underlying mechanisms of tumor hypoxia, the spatial distribution
      of hypoxic cells in relation to the vasculature was studied. In a panel of three
      human glioma xenograft lines (E2, E102, E106) with different growth
      characteristics, tumor line-specific patterns of hypoxia (pimonidazole) and
      (functional) vasculature (Hoechst 33342) were observed. Two of the three glioma
      lines showed a more homogeneous distribution of perfused vessels (E102 and E106)
      than the third glioma line (E2). Although all tumors showed hypoxia, the distance
      at which the steepest part of the gradient of the hypoxia marker was found varied
      significantly among the different glioma lines. The faster-growing E102 tumors
      had the longest distance (>300 microm). These results indicate that tumor line
      specific factors, rather than vascular geometry alone, may determine the
      oxygenation status of a tumor. As a consequence, vascular density cannot be used
      as a surrogate parameter for tumor hypoxia when comparing different tumors.
      Additional hypoxia and perfusion markers will further improve our understanding
      of changes in tumor physiology at the microregional level explaining the
      relationship between the low oxygen levels and the response of tumors to
      treatment.

PMID- 12005541
TI  - Vascular-targeted radioimmunotherapy with the alpha-particle emitter 211At.
AB  - Astatine-211, an alpha-particle emitter, was employed in a model system for
      vascular-targeted radioimmunotherapy of small tumors in mouse lung to compare its
      performance relative to other radioisotopes in the same system. Astatine-211 was
      coupled to the lung blood vessel-targeting monoclonal antibody 201B with N
      succinimidyl N-(4-[211At]astatophenethyl) succinamate linker. Biodistribution
      data showed that the conjugate delivered 211At to the lung (260-418% ID/g), where
      it remained with a biological half-time of about 30 h. BALB/c mice bearing about
      100 lung tumor colonies of EMT-6 cells, each about 2000 cells in size, were
      treated with 211At-labeled monoclonal antibody 201B. The administered activity of
      185 kBq per animal extended the life span of treated mice over untreated
      controls. Injections of 370 kBq, corresponding to an absorbed dose of 25-40 Gy,
      were necessary to eradicate all of the lung tumors. Mice receiving 740 kBq of
      211At-labeled monoclonal antibody 201B developed pulmonary fibrosis 3-4 months
      after treatment, as did mice treated with 3700 kBq of the alpha-particle emitter
      213Bi-labeled monoclonal antibody 201B in previous work. Animals that were
      injected with 211At bound to untargeted IgG or to glycine, as control agents,
      also demonstrated therapeutic effects relative to untreated controls. Control
      groups that received untargeted 211At required about twice as much administered
      activity for effective therapy as did groups with lung-targeted radioisotope.
      These results were not consistent with radioisotope biodistribution and dosimetry
      calculations that indicated that lung-targeted 211At should be at least 10-fold
      more efficient for lung colony therapy than 211At bound to nontargeting controls.
      The data showed that 211At is useful for vascular-targeted radioimmunotherapy
      because lung tumor colonies were eradicated in the mice. Work in this model
      system demonstrates that vascular targeting of alpha-particle emitters is an
      efficient therapy for small perivascular tumors and may be applicable to human
      disease when specific targeting agents are identified.

PMID- 12005542
TI  - Administration of recombinant human IL11 after supralethal radiation exposure
      promotes survival in mice: interactive effect with thrombopoietin.
AB  - In the present study, we evaluated the therapeutic potential of recombinant human
      IL11 in lethally irradiated C57BL6/J mice exposed to gamma rays. IL11
      administered for 5 consecutive days beginning 2 h after total-body irradiation
      with 8 or 9 Gy 60Co gamma rays resulted in a significant increase in 30-day
      survival. When IL11 was administered, only a slight improvement in the
      hematopoietic status (both blood cell counts and progenitor cells) was observed
      after an 8-Gy exposure, and no improvement in hematopoietic reconstitution was
      observed after 9 Gy total-body irradiation. The enhancement of fibrinogen in the
      plasma of irradiated animals suggested the importance of infections in the death
      of animals. IL11 was able to limit the increase in fibrinogen levels. However,
      prevention of bacterial infections by antibiotic treatment, although it delayed
      death, was ineffective in promoting survival either in placebo-treated and IL11
      treated mice. IL11 was administered along with thrombopoietin (TPO) or bone
      marrow transplantation to limit the hematopoietic syndrome, in addition to
      antibiotic treatment. When IL11 was combined with TPO, a potent stimulator of
      hematopoiesis, the survival of animals which had been irradiated with 10 Gy 137Cs
      gamma rays was increased significantly compared to those treated with IL11 or TPO
      alone. Furthermore, an interactive effect of TPO and IL11 on hematopoietic
      reconstitution was observed. Similarly, IL11 in combination with bone marrow
      transplantation enhanced survival after 15 Gy 137Cs gamma rays. These data
      suggest that the effect of IL11 on the hematopoietic system is only moderate when
      it is used alone in supralethally irradiated mice but that the effect is improved
      in the presence of a hematopoietic growth factor or bone marrow transplantation.

PMID- 12005543
TI  - Hspa4 (HSP70) is involved in the radioadaptive response: results from mouse
      splenocytes.
AB  - In a continuation of our earlier study on the involvement of HSP25 (now known as
      Hspb1) and HSP70 (now known as Hspa4) in the induction of an adaptive response,
      we examined the involvement of these proteins in the induction of the adaptive
      response using an animal model system. C57BL6 mice were irradiated with 5 cGy of
      gamma radiation three times in 1 week (for a total of 15 cGy), and a high
      challenge dose (6 Gy) was given on the day after the last low-dose irradiation.
      The survival time of the low-dose preirradiated mice was increased to 30%. The
      induction of apoptosis induced by 6 Gy was also reduced by this low-dose
      preirradiation regimen. To elucidate any link existing between the HSPs and the
      induction of the adaptive response, reverse transcriptase (RT)-polymerase chain
      reaction (PCR) analysis was performed using splenocytes. High-dose radiation up
      regulated the expression of Hspb1 and especially Hspa4, while expression of other
      HSPs such as HSC70 (now know as Hspa8), Hsp90, and alphaB-crystalline (now known
      as Cryab) did not change. When splenocytes from Hspa4 transgenic mice were
      preirradiated with a low dose of radiation, a reduction in cell death after high
      dose irradiation was observed. These results suggest that Hspa4 is a key molecule
      in the induction of the adaptive response.

PMID- 12005544
TI  - Radioprotection of lungs by amifostine is associated with reduction in
      profibrogenic cytokine activity.
AB  - Radiation-induced pulmonary toxicity causes significant morbidity and mortality
      in patients irradiated for lung cancer, breast cancer, lymphoma or thymoma.
      Amifostine is an important drug in the emerging field of cytoprotection. Recent
      advances in our understanding of the mechanism of radiation-induced injury at the
      molecular and cellular levels have stimulated interest in the development of
      effective radioprotective strategies. Accumulation of macrophages with associated
      production of reactive oxygen species (ROS) and production and activation of
      cytokines is a key process involved in the pathophysiology of radiation injury in
      the lung. The purpose of this study was to determine whether the mechanism of
      radioprotection by amifostine includes reduction in both macrophage activity and
      the expression and activation of profibrogenic cytokines. Our results
      demonstrated a reduction in both functional and histological radiation-induced
      lung injury by amifostine. In addition, this study is the first to demonstrate
      that amifostine given prior to irradiation reduced both the accumulation of
      macrophages and the expression/activation of lung tissue Tgfb1 which was followed
      by the reduction of plasma Tgfb1 levels during the development of radiation
      induced lung injury. Future studies are needed to determine whether
      administration of amifostine both during and after radiotherapy may further
      increase its radioprotective effect.

PMID- 12005545
TI  - Persistent induction of somatic reversions of the pink-eyed unstable mutation in
      F1 mice born to fathers irradiated at the spermatozoa stage.
AB  - Untargeted mutation and delayed mutation are features of radiation-induced
      genomic instability and have been studied extensively in tissue culture cells.
      The mouse pink-eyed unstable (p(un)) mutation is due to an intragenic duplication
      of the pink-eyed dilution locus and frequently reverts back to the wild type in
      germ cells as well as in somatic cells. The reversion event can be detected in
      the retinal pigment epithelium as a cluster of pigmented cells (eye spot). We
      have investigated the reversion p(um) in F1 mice born to irradiated males.
      Spermatogonia-stage irradiation did not affect the frequency of the reversion in
      F1 mice. However, 6 Gy irradiation at the spermatozoa stage resulted in an
      approximately twofold increase in the number of eye spots in the retinal pigment
      epithelium of F1 mice. Somatic reversion occurred for the paternally derived
      p(un) alleles. In addition, the reversion also occurred for the maternally
      derived, unirradiated p(un) alleles at a frequency equal to that for the
      paternally derived allele. Detailed analyses of the number of pigmented cells per
      eye spot indicated that the frequency of reversion was persistently elevated
      during the proliferation cycle of the cells in the retinal pigment epithelium
      when the male parents were irradiated at the spermatozoa stage. The present study
      demonstrates the presence of a long-lasting memory of DNA damage and the
      persistent up-regulation of recombinogenic activity in the retinal pigment
      epithelium of the developing fetus.

PMID- 12005546
TI  - Malignant neoplasms after radiation therapy for peptic ulcer.
AB  - Most information on radiation-related cancer risk comes from the Life Span Study
      (LSS) of the Japanese atomic bomb survivors. Stomach cancer mortality rates are
      much higher in Japan than in the U.S., making the applicability of LSS findings
      to the U.S. population uncertain. A unique cohort of U.S. patients who were
      irradiated for peptic ulcer to control gastric secretion provides a different
      perspective on risk. Cancer mortality data were analyzed and relative risks
      estimated for 3719 subjects treated by radiotherapy (mean stomach dose 14.8 Gy)
      and/or by surgery and medication during the period 1936-1965 and followed through
      1997 (average 25 years). Compared to the U.S. rates, stomach cancer mortality was
      significantly increased for irradiated and nonirradiated patients
      (observed/expected = 3.20 and 1.52, respectively). We observed strong evidence of
      exposure-related excess mortality from cancer of the stomach (RR 2.6, 95% CI 1.3,
      5.1), pancreas (RR 2.7, 95% CI 1.5, 5.1), and lung (RR 1.5, 95% CI 1.1, 2.1),
      with commensurate radiation dose responses in analyses that included nonexposed
      patients. However, the dose responses for these cancers were not significant when
      restricted to exposed patients. Our excess relative risk per gray estimate of
      0.20 at doses <or=10 Gy (95% CI 0, 0.73) is consistent with the estimate of 0.24
      (95% CI 0.10, 0.40) obtained from the LSS study with the linear model.

PMID- 12005547
TI  - Persistence of micronuclei in lymphocytes of cancer patients after radiotherapy.
AB  - To verify the applicability of the micronucleus (MN) yield in peripheral blood
      lymphocytes (PBLs) as a quantitative biodosimeter for monitoring in vivo ionizing
      radiation damage, we applied the cytokinesis-blocked micronucleus assay in PBLs
      of cancer patients treated with partial-body radiotherapy. Dosimetric information
      on these 13 patients represented a wide range in the number of fractions,
      cumulative tumor dose, total integral dose, and equivalent total-body absorbed
      dose. We found in PBLs of these patients that (1) the MN yield increased linearly
      with the equivalent total-body absorbed dose (r = 0.8, P = 0.002), (2) the
      distributions of the MN yields deviated significantly from Poisson, and (3) there
      was a general decline in MN yields with increasing length of follow-up, but with
      considerable variation between individuals. The average rate of decline was found
      to be linear and was correlated with the equivalent total-body absorbed dose (r =
      0.7, P = 0.007). Further, at 19-75 months of follow-up time, seven patients
      showed higher MN yields than their respective levels before radiotherapy,
      indicating the persistence of radiation-induced residual cytogenetic damage. Our
      findings suggest that the MN yield in human PBLs offers a reliable acute and
      perhaps chronic biodosimeter for in vivo radiation dose estimation. After the
      completion of radiotherapy, the persistence of elevated MN yield in PBLs is a
      reflection of the surviving population of radiation-induced genetically aberrant
      cells.

PMID- 12005548
TI  - Radiation-induced changes in permeability in unilamellar phospholipid liposomes.
AB  - Gamma-radiation-induced oxidative damage in unilamellar
      dipalmitoylphosphatidylcholine liposomes was investigated using a fluorescence
      technique. Liposomal changes in permeability induced by gamma radiation were
      monitored by measuring the leakage of pre-encapsulated 6-carboxyfluorescein, and
      alterations in lipid bilayer fluidity were determined by 1,6-diphenyl-1,3,5
      hexatriene fluorescence polarization. The changes in permeability and fluidity in
      the bilayer were found to be dependent on the radiation dose in a biphasic
      fashion. The results are interpreted in terms of lipid bilayer fluidization after
      exposure to doses up to 1 kGy, but rigidization of the bilayer at higher doses.
      These results indicate a relationship between alterations in permeability and
      fluidity in the lipid bilayer after irradiation. The vesicles were protected
      significantly against radiation-induced oxidative damage in the presence of alpha
      tocopherol and ascorbic acid. Radiation-induced changes in the permeability of
      the liposomes after exposure to gamma radiation and their modification by
      antioxidants indicate the involvement of a free radical mechanism in the
      production of damage, which may offer new insights in to the modification of
      cellular radiosensitivity by modulation of membrane damage.

PMID- 12005549
TI  - A new method specifically designed to expose cells isolated in vitro to radon and
      its decay products.
AB  - A system was set up to provide direct exposure of cells cultured in vitro to
      radon and its decay products. Radon gas emanating from a uranium source was
      introduced at a measured concentration in a closed 10-m(3) exposure chamber.
      Cells were cultured on the microporous membrane of an insert that was floating
      over the culture medium in a six-well cluster plate. Plates with cells were
      placed in an open thermoregulated bath within the chamber. Under these
      conditions, cells were irradiated by direct deposition of radon and radon decay
      products. During exposure, all parameters, including radon gas concentrations,
      decay product activities, and potential alpha-particle energy concentrations,
      were determined by periodic air-grab samplings inside the chamber. The energy
      spectrum of deposited decay products was characterized. An estimation of alpha
      particle flux density on the area containing cells was performed using CR-39
      detector films that were exposed in cell-free wells during the cell exposure. The
      number of alpha-particle traversals per cell was deduced both from the mean
      number of CR-39 tracks per surface unit and from measurements of entire cells or
      nuclear surfaces. This paper describes the design of experiment, the dosimetry of
      radon and radon decay product, and the procedures for aerosol measurements. Our
      preliminary data show the usefulness of the in vitro cell culture approach to the
      study of the early cellular effects of radon and its decay products.

PMID- 12005550
TI  - Quantitative subcellular secondary ion mass spectrometry (SIMS) imaging of boron
      10 and boron-11 isotopes in the same cell delivered by two combined BNCT drugs:
      in vitro studies on human glioblastoma T98G cells.
AB  - Ion microscopy was used for subcellular quantitative imaging of the isotopes 10B
      and 11B in the same cell to evaluate boron delivery using a mixture of two
      neutron capture therapy drugs, p-boronophenylalanine-fructose (BPA-F) and sodium
      borocaptate (BSH). The application of 10B-labeled BPA-F and 11B-labeled BSH
      allowed independent imaging of both 10B and 11B in the same cell using a CAMECA
      IMS-3f ion microscope. Mixed-drug treatments were compared to single-drug
      exposures given under identical conditions. 10BPA-F delivered 10B heterogeneously
      to T98G human glioblastoma cells, with a significantly reduced concentration in
      an organelle-rich perinuclear region. The intracellular distribution of 11B from
      11BSH contrasted with that of the 10B from 10BPA-F, with 11B distributed nearly
      homogeneously throughout cells. The subcellular distributions of 10B and 11B were
      sustained in mixed-drug treatments and resembled their localizations after the
      single-drug treatments. In both single- and mixed-drug treatments, cellular
      levels of 10B from 10BPA-F nearly doubled between 1 h and 6 h, with a 3:1
      intracellular to nutrient medium partitioning, while cellular levels of 11BSH
      remained essentially unchanged. The net effect of the combined treatment with
      10BPA-F and 11BSH was an additive delivery of boron to cells. This study
      introduces a novel approach for checking potential synergistic, antagonistic or
      simple additive delivery of two mixed boronated compounds in cellular/subcellular
      compartments.

PMID- 12005551
TI  - Radiation-induced DNA breaks in different human satellite DNA sequence areas,
      analyzed by DNA breakage detection-fluorescence in situ hybridization.
AB  - Human blood leukocytes were exposed to X rays to analyze the initial level of DNA
      breakage induced within different satellite DNA sequence areas and telomeres,
      using the DNA breakage detection-FISH procedure. The satellite DNA families
      analyzed comprised alphoid sequences, satellite 1, and 5-bp classical satellite
      DNA sequences from chromosome 1 (D1Z1 locus), from chromosome 9 (D9Z3 locus), and
      from the Y chromosome (DYZ1 locus). Since the control hybridization signal was
      quite different in each of the DNA targets, the relative increase in whole
      fluorescence intensity with respect to unirradiated controls was the parameter
      used for comparison. Irradiation of nucleoids obtained after protein removal
      demonstrated that the alkaline unwinding solution generates around half the
      amount of signal when breaks are present in the 5-bp classical DNA satellites as
      when the same numbers of breaks are present the genome overall, whereas the
      signal is slightly stronger when the breaks are within the alphoids or satellite
      1 sequences. After correction for differences in sensitivity to the alkaline
      unwinding-renaturation, DNA housed in chromatin corresponding to 5-bp classical
      satellites proved to be more sensitive to breakage than the overall genome,
      whereas DNA in the chromatin corresponding to alphoids or satellite 1 showed a
      sensitivity similar to that of the whole genome. The minimum detectable dose was
      0.1 Gy for the whole genome, 0.2 Gy for alphoids and satellite 1, and 0.4 Gy for
      the 5-bp classical satellites. Telomeric DNA sequences appeared to be maximally
      labeled in unirradiated cells. Thus telomeric ends behave like DNA breaks,
      constituting a source of background in alkaline unwinding assays.

PMID- 12005552
TI  - Rejoining of radiation-induced DNA double-strand breaks: pulsed-field
      electrophoresis analysis of fragment size distributions after incubation for
      repair.
AB  - The repair of radiation-induced DNA double-strand breaks (DSBs) is frequently
      investigated by measuring the time-dependent decrease in the fraction of
      fragmented DNA that is able to enter electrophoresis gels. When transformed into
      equivalent doses without repair, such measurements are thought to reflect the
      removal of DSBs, and they typically exhibit a fast initial component and a
      decreasing rate at longer repair intervals. This formalism, however, assumes that
      the spatial distribution of unrejoined breakage resembles the pattern of
      induction of DSBs. While the size distributions for initial fragmentation, such
      as that resolved by conventional pulsed-field gel electrophoresis (PFGE) (between
      about 10(5) and 10(7) bp), are well known to agree with the prediction of random
      breakage, no data are available from studies explicitly testing this relationship
      for residual breakage. Therefore, Chinese hamster V79 cells and MeWo (human
      melanoma) cells were irradiated with different doses (10-100 Gy) or were
      incubated for repair for up to 4 h after a single dose of 100 Gy (V79) or 90 Gy
      (MeWo) before being subjected to PFGE. Fragment size distributions were
      calculated by convolution of the PFGE profiles with an appropriately generated
      size calibration function. The results clearly demonstrate an over-representation
      of smaller fragments (below about 2-3 Mbp) compared to the prediction of
      randomness for residual breakage. In consequence, the time-dependent decrease of
      dose-equivalent values calculated from data on the fraction released may not
      directly reflect DSB rejoining rates. The present findings are compatible with an
      earlier suggestion of slow rejoining of breaks which have been induced as
      multiple breaks (two or more) in large chromosomal loops, thus also predicting an
      increase of the slowly rejoining DSB fraction with increasing dose.

PMID- 12005553
TI  - Rapid fluorescence ratio assay for detecting changes in radiosensitivity.
AB  - To test modifications in sensitization to radiation or drugs in preclinical
      studies of cancer therapy, the colony-forming assay is regarded as the gold
      standard. Because this assay is time consuming, somewhat laborious, and
      unsuitable for rapid screening, development of other assays is desirable. We
      describe here an assay based on the detection of enhanced green fluorescence
      protein (EGFP) with flow cytometry that is particularly suitable for genetic
      manipulation studies in which the gene of interest is introduced together with
      EGFP as reporter. It is easily adaptable to other reporters, however, whether
      naturally fluorescent or requiring immunochemical staining. Cells are irradiated
      as mixed populations of a known standard cell line (nonfluorescent) together with
      the genetically manipulated cell line expressing EGFP. Ratios of fluorescent and
      nonfluorescent cells are measured before treatment and several days after
      treatment. If the cell populations have equal radiosensitivities, the ratio
      remains unchanged. Changes in the ratio indicate changes in radiosensitivity. The
      assay was validated for two situations in which dominant negative peptides
      inhibiting DNA repair were expressed in A549 human lung cells and affected
      radiosensitivity.

PMID- 12005554
TI  - Naturalness bounds on dipole moments from new physics.
AB  - Assuming naturalness that the quantum corrections to the mass should not exceed
      the order of the observed mass, we derive and apply model-independent bounds on
      the anomalous magnetic moments and electric dipole moments of leptons and quarks
      due to new physics.

PMID- 12005555
TI  - Next-to-next-to-leading order Higgs production at Hadron Colliders.
AB  - The Higgs-boson production cross section at pp and pp colliders is calculated in
      QCD at next-to-next-to-leading order (NNLO). We find that the perturbative
      expansion of the production cross section is well behaved and that scale
      dependence is reduced relative to the NLO result. These findings give us
      confidence in the reliability of the prediction. We also report an error in the
      NNLO correction to Drell-Yan production.

PMID- 12005557
TI  - Pion propagation near the QCD chiral phase transition.
AB  - We point out that, in analogy with spin waves in antiferromagnets, all parameters
      describing the real-time propagation of soft pions at temperatures below the QCD
      chiral phase transition can be expressed in terms of static correlators. This
      allows, in principle, the determination of the soft pion dispersion relation on
      the lattice. Using scaling and universality arguments, we determine the critical
      behavior of the parameters of pion propagation. We predict that, when the
      critical temperature is approached from below, the pole mass of the pion drops
      despite the growth of the pion screening mass. This fact is attributed to the
      decrease of the pion velocity near the phase transition.

PMID- 12005556
TI  - Pseudorapidity distributions of charged particles from Au + Au collisions at the
      maximum RHIC energy, square root[s(NN)] = 200 GeV.
AB  - We present charged-particle multiplicities as a function of pseudorapidity and
      collision centrality for the 197Au+197Au reaction at square root[s(NN)] = 200
      GeV. For the 5% most central events we obtain dN(ch)/deta/(eta = 0) = 625+/-55
      and N(ch)/(-4.7< or =eta < or =4.7) = 4630 +/- 370, i.e., 14% and 21% increases,
      respectively, relative to square root[s(NN)] = 130 GeV collisions. Charged
      particle production per pair of participant nucleons is found to increase from
      peripheral to central collisions around midrapidity. These results constrain
      current models of particle production at the highest RHIC energy.

PMID- 12005558
TI  - Absence of thermophoretic flow in relativistic heavy-ion collisions as an
      indicator for the absence of a mixed phase.
AB  - If a quark-gluon plasma is formed in relativistic heavy-ion collisions, there may
      or may not be a mixed phase of quarks, gluons, and hadronic clusters when the
      critical temperature is reached in the expansion of the fireball. If there is a
      temperature gradient in the fireball, the hadronic clusters, embedded in the heat
      bath of quarks and gluons, would be subjected to a thermophoretic force. It is
      shown that, even for small temperature gradients and short lifetimes of the mixed
      phase, thermophoresis would lead to a flow essentially stronger than the observed
      one. The absence of this strong flow provides support for a rapid or sudden
      hadronization mechanism without a mixed phase.

PMID- 12005559
TI  - Deuteron breakup in the 2H(e,e' p) reaction at low momentum transfer and close to
      threshold.
AB  - Deuteron breakup has been studied in a 2H(e,e' p) coincidence experiment at low
      momentum transfer and for energies close to threshold. The longitudinal-plus
      transverse ( L+T) and longitudinal-transverse ( LT) interference cross sections
      are deduced. Nonrelativistic calculations based on the Bonn potential and
      including leading order relativistic contributions, meson exchange currents, and
      isobar configurations describe the ( L+T) data well. Surprisingly, large
      deviations of 30% to 45% are observed for the LT contribution.

PMID- 12005560
TI  - Overpopulation of Omega; in pp collisions: a way to distinguish statistical
      hadronization from string dynamics.
AB  - The Omega/Omega ratio originating from string decays is predicted to be larger
      than unity in proton-proton interactions at SPS energies ( E(lab) = 160 GeV). The
      antiomega dominance increases with decreasing beam energy. This surprising
      behavior is caused by the combinatorics of quark-antiquark production in small
      and low-mass strings. Since this behavior is not found in a statistical
      description of hadron production in proton-proton collisions, it may serve as a
      key observable to probe the hadronization mechanism in such collisions.

PMID- 12005561
TI  - Phase control of nonadiabaticity-induced quantum chaos in an optical lattice.
AB  - The qualitative nature (i.e., integrable vs chaotic) of the translational
      dynamics of a three-level atom in an optical lattice is shown to be controllable
      by varying the relative laser phase of two standing-wave lasers. Control is
      explained in terms of the nonadiabatic transition between optical potentials and
      the corresponding regular-to-chaotic transition in mixed classical-quantum
      dynamics. The results are of interest to both areas of coherent control and
      quantum chaos.

PMID- 12005562
TI  - Photoexcitation of a dipole-forbidden resonance in helium.
AB  - We have observed photoexcitation of the dipole-forbidden 1s(2) 1S0-->2p(2) 1D2
      resonance in helium by measuring the nondipolar forward-backward asymmetry of
      photoelectron angular distributions in the 2l2l(') autoionizing region. By
      exploiting the electric dipole-quadrupole interference in the excitation of both
      the 2s2p 1P1 and 2p(2) 1D2 levels, we have observed the quadrupole resonance in
      photoabsorption and extracted its Fano line shape parameters and the relative
      phase of the 1sEp and 1sEd continua. We find the quadrupole line profile index
      q(2) to be markedly different from theoretical expectations.

PMID- 12005563
TI  - Surpassing the standard quantum limit for optical imaging using nonclassical
      multimode light.
AB  - Using continuous wave superposition of spatial modes, we demonstrate
      experimentally displacement measurement of a light beam below the standard
      quantum limit. Multimode squeezed light is obtained by mixing a vacuum squeezed
      beam and a coherent beam that are spatially orthogonal. Although the resultant
      beam is not squeezed, it is shown to have strong internal spatial correlations.
      We show that the position of such a light beam can be measured using a split
      detector with an increased precision compared to a classical beam. This method
      can be used to improve the sensitivity of small displacement measurements.

PMID- 12005564
TI  - Generation of single intense short optical pulses by ultrafast molecular phase
      modulation.
AB  - Pulses with durations below 4 fs have been generated using the method of
      ultrafast molecular phase modulation. A laser pulse shorter than the molecular
      vibrational or rotational period obtains spectral broadening during propagation
      along a hollow waveguide filled with previously impulsively excited Raman active
      gases. The induced time dependent phase, frequency, and frequency chirp are
      controllable by changing the delay between excitation and probe pulse within the
      molecular vibrational period.

PMID- 12005565
TI  - Coherent light transport in a cold strontium cloud.
AB  - We study light coherent transport in the weak localization regime using magneto
      optically cooled strontium atoms. The coherent backscattering cone is measured in
      the four polarization channels using light resonant with a J(g) = 0-->J(e) = 1
      transition of the strontium atom. We find an enhancement factor close to 2 in the
      helicity preserving channel, in agreement with theoretical predictions. This
      observation confirms the effect of internal structure as the key mechanism for
      the contrast reduction observed with a rubidium cold cloud [G. Labeyrie et al.,
      Phys. Rev. Lett. 83, 5266 (1999)]. Experimental results are in good agreement
      with Monte Carlo simulations taking into account geometry effects.

PMID- 12005566
TI  - Phase separation and coarsening in electrostatically driven granular media.
AB  - A continuum model for the phase separation and coarsening in electrostatically
      driven granular media is formulated in terms of a Ginzburg-Landau equation
      subject to conservation of the total number of grains. In the regime of well
      developed clusters, the continuum model is used to derive "sharp-interface"
      equations that govern the dynamics of the interphase boundary. The model captures
      the essential physics of this system.

PMID- 12005567
TI  - Two-phase densification of cohesive granular aggregates.
AB  - When poured into a container, cohesive granular materials form low-density, open
      granular aggregates. If pressure is applied to these aggregates, they densify by
      particle rearrangement. Here we introduce experimental and computational results
      suggesting that densification by particle rearrangement occurs in the form of a
      phase transition between two configurational phases of the aggregate. Then we
      show that the energy landscape associated with particle rearrangement is
      nonconvex and therefore consistent with our interpretation of the experimental
      and computational results. Our conclusions are relevant to many technological
      processes and natural phenomena.

PMID- 12005568
TI  - Coarsening dynamics of striped patterns in thin granular layers under vertical
      vibration.
AB  - The process of pattern formation in granular layers was experimentally studied.
      Ten layers of granular materials inside a vacuum container were placed under a
      vertical vibration of A sin2pi f t. Control parameters were the dimensionless
      acceleration Gamma = A(2pi f)(2)/g and vibration frequency f. When the system was
      quenched from a flat pattern state to a striped pattern state by instantly
      increasing Gamma, there were more than 10(4) periods before a full steady striped
      pattern appeared. This nonequilibrium and nonsteady process showed dynamic
      scaling behavior. The growth exponent of the characteristic length scale of the
      ordered domain was 0.25, which agrees with that of the Swift-Hohenberg system.

PMID- 12005569
TI  - Transition in the dynamics of a diffusive running sandpile.
AB  - A running sandpile is shown to undergo a dynamical transition as diffusion is
      increased from zero. The transition takes place after the local diffusion has
      become so large as to erase the local inhomogeneities, caused by the intermittent
      rain of sand, before they can trigger avalanche activity. The system then
      undergoes an abrupt change with the self-similar structure of the dynamics being
      replaced with quasiperiodic, near system-size transport events. These results may
      have significant implications for many of the driven physical systems for which
      self-organized criticality based dynamical models have been proposed.

PMID- 12005570
TI  - Experimental characterization of nonlinear harmonic radiation from a visible self
      amplified spontaneous emission free-electron laser at saturation.
AB  - Nonlinear harmonic radiation was observed using the VISA self-amplified,
      spontaneous emission (SASE) free-electron laser (FEL) at saturation. The gain
      lengths, spectra, and energies of the three lowest SASE FEL modes were
      experimentally characterized. The measured nonlinear harmonic gain lengths and
      center spectral wavelengths decrease with harmonic number, n, which is consistent
      with nonlinear harmonic theory. Both the second and third nonlinear harmonics
      energies are about 1% of the fundamental energy. These experimental results
      demonstrate for the first time the feasibility of using nonlinear harmonic SASE
      FEL radiation to produce coherent, femtosecond x rays.

PMID- 12005571
TI  - Radial transport and electron-cyclotron-current drive in the TCV and DIII-D
      tokamaks.
AB  - Calculation of electron-cyclotron-current drive (ECCD) with the comprehensive
      CQL3D Fokker-Planck code for a TCV tokamak shot gives 550 kA of driven toroidal
      current, in marked disagreement with the 100-kA experimental value. Published
      ECCD efficiencies calculated with CQL3D in the much larger, higher-confinement
      DIII-D tokamak are in excellent agreement with experiment. The disagreement is
      resolved by including in the calculations electrostatic-type radial transport at
      levels given by global energy confinement in tokamaks. The radial transport of
      energy and toroidal current are in agreement.

PMID- 12005572
TI  - Confinement of nonneutral plasmas on magnetic surfaces.
AB  - The confinement of a nonneutral plasma in a magnetic-surface, or stellarator,
      configuration is explored. The fluid equilibrium equations are derived and are
      found to be fundamentally different from previous results. Diocotron modes are
      predicted to be stable. The collisional confinement time can be very long.
      Possible applications include positron trapping and confinement of positron
      electron plasmas. The basic physics can be addressed experimentally in the simple
      tabletop stellarator planned for construction at Columbia University.

PMID- 12005573
TI  - Melting of crystalline confined plasmas.
AB  - The melting of cold, ordered arrays of up to 10 000 charges, confined in external
      fields, has been studied in simulations. The latent heat associated with melting
      and the behavior of the specific heat were obtained, along with the spatial
      correlation function g(r) with respect to neighbors and the diffusion rates, both
      as a function of temperature. The melting temperatures of finite arrays of ions
      are found to be lower than that for infinite Coulombic matter, by an amount that
      depends on the number of charges and on the fraction of ions in the surface
      layer, in particular.

PMID- 12005574
TI  - Entropy-driven triple point wetting in hard-rod mixtures.
AB  - We theoretically study binary mixtures of thin and thick hard rods with diameter
      ratio more extreme than 1:4. The bulk phase diagram of these systems exhibits a
      triple point, where an isotropic (I) phase coexists with two nematic phases ( N1
      and N2) of different composition. Using density functional theory, we predict
      that the I-N2 interface is completely wet by N1 upon approach of the the I-N1-N2
      triple point. This entropic triple point wetting should be experimentally
      observable in colloidal suspensions of rodlike particles.

PMID- 12005575
TI  - Metastability of amorphous silicon from silicon network rebonding.
AB  - We propose a network rebonding model for light-induced metastability in amorphous
      silicon, involving bonding rearrangements of silicon and hydrogen atoms.
      Nonradiative recombination breaks weak silicon bonds and generates dangling bond
      floating bond pairs, with very low activation energies. The transient floating
      bonds annihilate, generating local hydrogen motion. Charged defects are also
      found. Support for these processes is found with tight-binding molecular dynamics
      simulations. The model accounts for major experimental features of the Staebler
      Wronski effect including electron-spin resonance data, the t(1/3) kinetics of
      defect formation, two types of metastable dangling bonds, and hysteretic
      annealing.

PMID- 12005576
TI  - Low-energy linear structures in dense oxygen: implications for the epsilon phase.
AB  - Using density functional theory implemented within the generalized gradient
      approximation, a new nonmagnetic insulating ground state of solid oxygen is
      proposed and found to be energetically favored at pressures corresponding to the
      epsilon phase. The newly predicted static ground state is composed of linear
      herringbone-type chains of O2 molecules and has Cmcm symmetry (with an
      alternative monoclinic cell). Importantly, this phase supports IR-active zone
      center phonons, and their computed frequencies are found to be in broad agreement
      with recent infrared absorption experiments.

PMID- 12005577
TI  - Hole formation in thin polymer films: a two-stage process.
AB  - Thin, supported liquid films are known to rupture, creating holes throughout the
      film, due to defects or to van der Waals interactions. We show that the hole
      formation process before rupturing occurs in two stages, each characterized by
      distinct dynamical and morphological features. The time scale for the formation
      process is orders of magnitude slower than the translational (reptation)
      relaxation time of the individual chains. This has implications regarding the
      transition from the formation regime to subsequent hole growth regime on the
      underlying substrate.

PMID- 12005578
TI  - Compression of carbon nanotubes filled with C60, CH4, or Ne: predictions from
      molecular dynamics simulations.
AB  - The effect of filling nanotubes with C60, CH4, or Ne on the mechanical properties
      of the nanotubes is examined. The approach is classical molecular dynamics using
      the reactive empirical bond order (REBO) and the adaptive intermolecular REBO
      potentials. The simulations predict that the buckling force of filled nanotubes
      can be larger than that of empty nanotubes, and the magnitude of the increase
      depends on the density of the filling material. In addition, these simulations
      demonstrate that the buckling force of empty nanotubes depends on temperature.
      Filling the nanotube disrupts this temperature effect so that it is no longer
      present in some cases.

PMID- 12005579
TI  - Microscopic model for thin film spreading.
AB  - A microscopic, driven lattice gas model is proposed for the dynamics and
      spatiotemporal fluctuations of the precursor film observed in spreading
      experiments. Matter is transported both by holes and particles, and the
      distribution of each can be described by driven diffusion with a moving boundary.
      This picture leads to a stochastic partial differential equation for the shape of
      the boundary. Explicit analytic results are obtained which agree with the
      simulations of the lattice gas.

PMID- 12005580
TI  - Low-temperature epitaxial growth of the quaternary wide band gap semiconductor
      SiCAlN.
AB  - Two compounds SiC and AlN, normally insoluble in each other below approximately
      2000 degrees C, are synthesized as a single-phase solid-solution thin film by
      molecular beam epitaxy at 750 degrees C. The growth of epitaxial SiCAlN films
      with hexagonal structure takes place on 6H-SiC(0001) substrates. Two structural
      models for the hexagonal SiCAlN films are constructed based on first-principles
      total-energy density functional theory calculations, each showing agreement with
      the experimental microstructures observed in cross-sectional transmission
      electron microscopy images. The predicted fundamental band gap is 3.2 eV for the
      stoichiometric SiCAlN film.

PMID- 12005581
TI  - Scaling and universality of self-organized patterns on unstable vicinal surfaces.
AB  - We propose a unified treatment of the step bunching instability during epitaxial
      growth. The scaling properties of the self-organized surface pattern are shown to
      depend on a single parameter, the leading power in the expansion of the biased
      diffusion current in powers of the local surface slope. We demonstrate the
      existence of universality classes for the self-organized patterning appearing in
      models and experiments.

PMID- 12005582
TI  - Interface stress in polycrystalline materials: the case of nanocrystalline Pd.
AB  - Based on a generalization of a capillary equation for solids, we develop a method
      for measuring the absolute value of grain-boundary stress in polycrystalline
      samples having a large interface-to-volume ratio. The grain-boundary stress in
      nanocrystalline Pd is calculated from x-ray diffraction measurements of the
      average grain size and the residual-strain-free lattice spacings, yielding a
      value of 1.2+/-0.1 N/m. The random distribution of crystallite orientations in
      the sample suggests that this value is characteristic of high-angle grain
      boundaries in Pd.

PMID- 12005583
TI  - Nucleation and bulk crystallization in binary phase field theory.
AB  - We present a phase field theory for binary crystal nucleation. In the one
      component limit, quantitative agreement is achieved with computer simulations
      (Lennard-Jones system) and experiments (ice-water system) using model parameters
      evaluated from the free energy and thickness of the interface. The critical
      undercoolings predicted for Cu-Ni alloys accord with the measurements, and
      indicate homogeneous nucleation. The Kolmogorov exponents deduced for dendritic
      solidification and for "soft impingement" of particles via diffusion fields are
      consistent with experiment.

PMID- 12005584
TI  - Atomic-scale structure of dislocations revealed by scanning tunneling microscopy
      and molecular dynamics.
AB  - The intersection between dislocations and a Ag(111) surface has been studied
      using an interplay of scanning tunneling microscopy (STM) and molecular dynamics.
      Whereas the STM provides atomically resolved information about the surface
      structure and Burgers vectors of the dislocations, the simulations can be used to
      determine dislocation structure and orientation in the near-surface region. In a
      similar way, the subsurface structure of other extended defects can be studied.
      The simulations show dislocations to reorient the partials in the surface region
      leading to an increased splitting width at the surface, in agreement with the STM
      observations. Implications for surface-induced cross slip are discussed.

PMID- 12005585
TI  - Excitonic condensation in a symmetric electron-hole bilayer.
AB  - Using diffusion Monte Carlo simulations we have investigated the ground state of
      a symmetric electron-hole bilayer and determined its phase diagram at T = 0. We
      find clear evidence of an excitonic condensate, whose stability however is
      affected by an in-layer electronic correlation. This stabilizes the electron-hole
      plasma at large values of the density or interlayer distance, and the Wigner
      crystal at low density and large distance. We have also estimated pair
      correlation functions and low-order density matrices to give a microscopic
      characterization of correlations as well as to try and estimate the condensate
      fraction.

PMID- 12005586
TI  - Spin-orbit coupling and electron spin resonance theory for carbon nanotubes.
AB  - A theoretical description of electron spin resonance (ESR) in 1D interacting
      metals is given, with primary emphasis on carbon nanotubes. The spin-orbit
      coupling is derived, and the resulting ESR spectrum is analyzed using a low
      energy field theory. Drastic differences in the ESR spectra of single-wall and
      multiwall nanotubes are found. For single-wall tubes, the predicted double peak
      spectrum is linked to spin-charge separation. For multiwall tubes, a single
      narrow asymmetric peak is expected.

PMID- 12005587
TI  - Solid state effects on exciton states and optical properties of PPV.
AB  - We perform ab initio calculations of optical properties for a typical
      semiconductor conjugated polymer, poly-para-phenylenevinylene, in both isolated
      chain and crystalline packing. In order to obtain results for excitonic energies
      and real-space wave functions we explicitly include electron-hole interaction
      within the density-matrix formalism. We find that the details of crystalline
      arrangement crucially affect the optical properties, leading to a richer exciton
      structure and opening nonradiative decay channels. This has implications for the
      optical activity and optoelectronic applications of polymer films.

PMID- 12005588
TI  - Imaging subsurface reflection phase with quantized electrons.
AB  - Lead quantum wells (QW) epitaxially grown on annealed Pb/Si(111) interface form a
      model system for the study of interactions between quantized electrons and
      adiabatically modulated boundaries. Tunnel spectra of this system reveal a
      previously unknown adiabatic shift of QW resonances due to lateral variations of
      the electronic reflection phase at the buried interface. With this effect,
      lateral distribution of the subsurface reflection phase can be probed, using
      scanning tunneling microscopy.

PMID- 12005589
TI  - Field-Tuned Superconductor-Insulator Transition with and without Current Bias.
AB  - The magnetic-field-tuned superconductor-insulator transition has been studied in
      ultrathin beryllium films quench condensed near 20 K. In the zero-current limit,
      a finite-size scaling analysis yields the scaling exponent product nuz = 1.35+/
      0.10 and a critical sheet resistance, R(c), of about 1.2R(Q), with R(Q) =
      h/4e(2). However, in the presence of dc bias currents that are smaller than the
      zero-field critical currents, nuz becomes 0.75+/-0.10. This new set of exponents
      suggests that the field-tuned transitions with and without a dc bias current
      belong to different universality classes.

PMID- 12005590
TI  - Model for superconductivity in ferromagnetic ZrZn2.
AB  - We propose that superconductivity in the ferromagnetic state of ZrZn2 is
      stabilized by an exchange-type interaction between the magnetic moments of
      triplet-state Cooper pairs and the ferromagnetic magnetization density. This
      explains why superconductivity occurs in the ferromagnetic state only, and why it
      persists deep into the ferromagnetic state. The model of this article also yields
      a particular order parameter symmetry, which is a prediction that can be checked
      experimentally.

PMID- 12005591
TI  - Critical field enhancement near a superconductor-insulator transition.
AB  - We have discovered a phenomenon where the orbital pair breaking effect is
      reduced, if not eliminated. It appears as a striking enhancement in the upper
      critical field H(c2) for (TMTSF)2PF6 and a strong upward curvature in the
      critical field versus temperature in the region of pressure-temperature phase
      space near the superconductor-spin density wave insulator boundary. A simple
      model based on self-consistently dividing the superconductor into layers explains
      the observations remarkably well and provides a unique way around orbital
      frustration and toward higher critical fields.

PMID- 12005592
TI  - Evidence for a nodeless gap from the superfluid density of optimally doped
      Pr(1.855)Ce(0.145)CuO(4-y) films.
AB  - We present measurements of the ab-plane magnetic penetration depth, lambda(T), in
      five optimally doped Pr(1.855)Ce(0.145)CuO(4-y) films for 1.6 K< or =T < or =T(c)
      approximately 24 K. Low resistivities, high superfluid densities n(s)(T)
      proportional, variant lambda(-2)(T), high T(c)'s, and small transition widths are
      reproducible and indicative of excellent film quality. For all five films,
      lambda(-2)(T)/lambda(-2)(0) at low T is well fitted by an exponential temperature
      dependence with a gap, Delta(min), of 0.85k(B)T(c). This behavior is consistent
      with a nodeless gap and is incompatible with d-wave superconductivity.

PMID- 12005593
TI  - Evidence of a d- to s-wave pairing symmetry transition in the electron-doped
      cuprate superconductor Pr(2-x)CexCuO4.
AB  - We present point contact spectroscopy (PCS) data for junctions between a normal
      metal and the electron-doped cuprate superconductor Pr(2-x)CexCuO4 (PCCO). For
      the underdoped compositions of this cuprate ( x approximately 0.13) we observe a
      peak in the conductance-voltage characteristics of the point contact junctions.
      The shape and magnitude of this peak suggest the presence of Andreev bound states
      at the surface of underdoped PCCO which is evidence for a d-wave pairing
      symmetry. For overdoped PCCO ( x approximately 0.17) the PCS data do not show any
      evidence of Andreev bound states at the surface suggesting an s-wave pairing
      symmetry.

PMID- 12005594
TI  - Evidence for a transition in the pairing symmetry of the electron-doped cuprates
      La(2-x)Ce(x)CuO(4-y) and Pr(2-x)Ce(x)CuO(4-y).
AB  - We present measurements of the magnetic penetration depth, lambda(-2)(T), in Pr(2
      x)Ce(x)CuO(4-y) and La(2-x)Ce(x)CuO(4-y) films at three Ce doping levels, x, near
      optimal. Optimal and overdoped films are qualitatively and quantitatively
      different from underdoped films. For example, lambda(-2)(0) decreases rapidly
      with underdoping but is roughly constant above optimal doping. Also, lambda(
      2)(T) at low T is exponential at optimal and overdoping but is quadratic at
      underdoping. In light of other studies that suggest both d- and s-wave pairing
      symmetry in nominal optimally doped samples, our results are evidence for a
      transition from d- to s-wave pairing near optimal doping.

PMID- 12005595
TI  - Direct observation of the modulation of the 4f-electron orbital state by strong p
      f mixing in CeSb.
AB  - Low-temperature x-ray diffraction experiment has been carried out to investigate
      the 4 f-electron state of the low carrier density system CeSb which shows
      complicated magnetic phase diagrams at low temperatures. The scattering pattern
      of the satellite peaks observed in the magnetically ordered state AFP3 is
      explained well by the model which takes into account both the lattice and charge
      modulations corresponding to the complex magnetic structure. The present result
      gives direct evidence for the strong modulation of the 4 f-electron orbital state
      in CeSb due to the combined effect of the strong p-f mixing and carrier
      localization.

PMID- 12005596
TI  - Large orbital moments and internal magnetic fields in lithium nitridoferrate(I).
AB  - The iron nitridometalates Li2[(Li(1-x)Fe(I)(x))N] display ferromagnetic ordering
      and spin freezing. Large magnetic moments up to 5.0mu(B)/Fe are found in the
      magnetization. In Mossbauer effect studies huge hyperfine magnetic fields up to
      696 kOe are observed at specific Fe sites. These extraordinary fields and moments
      originate in an unusual ligand field splitting for those Fe species leading
      [within local spin density approximation (LSDA)] to a localized orbitally
      degenerate doublet. Including spin-orbit interaction and strong intra-atomic
      electron correlation (LDA+SO+U) gives rise to a large orbital momentum.

PMID- 12005597
TI  - Strong anisotropy of projected 3d moments in epitaxial CrO2 films.
AB  - Soft x-ray magnetic circular dichroism (XMCD) spectra have been investigated for
      different crystallographic projections of CrO2. Strong anisotropic orbital Cr 3d
      contributions and a change of sign of the XMCD signal is observed and attributed
      to t(2g) majority states near the Fermi level. Additionally, moment analysis
      exhibits anisotropic behavior in the projected spin contributions of CrO2
      assigned to a strong magnetic dipole term T(z), consistent with an intrinsic
      magnetic easy axis behavior along the CrO2 [001] axis. A reduced projected
      isotropic Cr 3d spin moment has been interpreted in terms of hybridization with
      oxygen.

PMID- 12005598
TI  - Light and electric field control of ferromagnetism in magnetic quantum
      structures.
AB  - A strong influence of illumination and electric bias on the Curie temperature and
      saturation value of the magnetization is demonstrated for semiconductor
      structures containing a modulation-doped p-type Cd(0.96)Mn(0.04)Te quantum well
      placed in various built-in electric fields. It is shown that both light beam and
      bias voltage generate an isothermal and reversible crossover between the
      paramagnetic and ferromagnetic phases, in the way that is predetermined by the
      structure design. The observed behavior is in quantitative agreement with the
      expectations for systems, in which ferromagnetic interactions are mediated by the
      weakly disordered two-dimensional hole liquid.

PMID- 12005599
TI  - Indications of intrinsic chemical and structural inhomogeneity in lightly doped
      La1-xSrxMnO3.
AB  - X-ray absorption fine structure measurements of the Sr and La K edges of the
      solid solution La(1-x)SrxMnO3 reveal a consistent deviation from a random
      distribution of Sr at the La/Sr sites for x less than or similar to 0.3. Local
      structural disorder on the cation sublattice in the low-x samples is also
      observed to differ in the vicinity of the La-rich and Sr-rich clusters. The local
      clustering and structural disorder establish an intrinsic chemical as well as
      structural inhomogeneity on the nanometer scale, which may provide a mechanism
      for the nucleation of magnetoelectronic phase separation.

PMID- 12005600
TI  - Ordering in Heisenberg spin glasses.
AB  - For five different Heisenberg spin glass systems, torque experiments were
      performed in applied magnetic fields up to 4 T. The Dzyaloshinski-Moriya random
      anisotropy strengths, the in-field torque onset temperatures, and the torque
      relaxation were measured. Critical exponents were estimated independently using a
      standard protocol. The data are strong evidence for a true spin glass ordered
      state which survives under high applied magnetic fields; they can be interpreted
      consistently in terms of a chiral ordering model with replica symmetry breaking
      as proposed by Kawamura and co-workers.

PMID- 12005601
TI  - Anomalous spin excitation spectrum of the Heisenberg model in a magnetic field.
AB  - Making the assumption that high-energy fermions exist in the two dimensional spin
      1/2 Heisenberg antiferromagnet, we present predictions based on the pi-flux
      ansatz for the dynamic structure factor when the antiferromagnet is subject to a
      uniform magnetic field. The main result is the presence of gapped excitations in
      a momentum region near (pi,pi) with energy lower than that at (pi,pi). This is
      qualitatively different from spin-wave theory predictions and may be tested by
      experiments or by quantum Monte Carlo.

PMID- 12005602
TI  - Anomalous Hall effect in ferromagnetic semiconductors.
AB  - We present a theory of the anomalous Hall effect in ferromagnetic (III, Mn)V
      semiconductors. Our theory relates the anomalous Hall conductance of a
      homogeneous ferromagnet to the Berry phase acquired by a quasiparticle wave
      function upon traversing closed paths on the spin-split Fermi surface. The
      quantitative agreement between our theory and experimental data in both (In,
      Mn)As and (Ga, Mn)As systems suggests that this disorder independent contribution
      to the anomalous Hall conductivity dominates in diluted magnetic semiconductors.
      The success of this model for (III, Mn)V materials is unprecedented in the
      longstanding effort to understand origins of the anomalous Hall effect in
      itinerant ferromagnets.

PMID- 12005603
TI  - Off-resonant fifth-order response function for two-dimensional Raman spectroscopy
      of liquids CS2 and H2O.
AB  - The off-resonant fifth-order response functions for two-dimensional (2D) Raman
      spectroscopy of molecular liquids CS2 and H2O are investigated by using molecular
      dynamics calculation. This spectroscopy, able to deal with a phase space
      dynamics, shows the existence of nodal lines in several polarization tensor
      elements [see L. Kaufman et al., Phys. Rev. Lett. 88, 207402 (2002) for
      experimental results]. The nodal property is found to arise from the dynamical
      couplings among rotational modes, not accounted for in a normal mode picture. The
      effects of anharmonicities and "mode coupling through polarizability" are also
      investigated by comparing the 2D Raman signal with a constant temperature
      velocity reassignment echo method.

PMID- 12005604
TI  - Heterodyne-detected fifth-order nonresonant Raman scattering from room
      temperature CS2.
AB  - Actively phase-locked heterodyne-detected fifth-order nonresonant Raman
      scattering from room temperature CS2 has been measured. The experimental signals
      have similar magnitudes, shapes, and sign changes as calculated responses
      obtained via molecular dynamics simulations [S. Saito and I. Ohmine, Phys. Rev.
      Lett. 88, 207401 (2002)]. The measured signals contain sign changes that appear
      to be associated with the coupling of rotational motions both to each other and
      to translational motions.

PMID- 12005605
TI  - Left-handed materials do not make a perfect lens.
AB  - By means of an analysis on evanescent waves in left-handed materials (LHM), we
      show that within a slab of such a medium, sandwiched between two positive
      refraction media, there is amplification of evanescent waves in ideal lossless,
      dispersiveless media; however, contrary to previous claims, this is limited to a
      finite width of the slab so that it prevents their restoration and perfect
      focusing. We illustrate this by considering their coupling to propagating waves
      through a tunnel barrier containing a slab of LHM. Further, we show that the
      effect of absorption, necessarily present in such materials, may drastically
      change any evanescent amplifying wave into a decaying one.

PMID- 12005606
TI  - Quantum nondemolition measurements of a qubit.
AB  - The concept of quantum nondemolition (QND) measurement is extended to coherent
      oscillations in an individual two-state system. Such a measurement enables direct
      observation of an intrinsic spectrum of these oscillations avoiding the detector
      induced dephasing that affects the standard (non-QND) measurements. The suggested
      scheme can be realized in Josephson-junction qubits which combine flux and charge
      dynamics.

PMID- 12005607
TI  - Creating decoherence-free subspaces using strong and fast pulses.
AB  - A decoherence-free subspace (DFS) isolates quantum information from deleterious
      environmental interactions. We give explicit sequences of strong and fast ["bang
      bang" (BB)] pulses that create the conditions allowing for the existence of DFSs
      that support scalable, universal quantum computation. One such example is the
      creation of the conditions for collective decoherence, wherein all system
      particles are coupled in an identical manner to their environment. The BB pulses
      needed for this are generated using only the Heisenberg exchange interaction. In
      conjunction with previous results, this shows that Heisenberg exchange is by
      itself an enabler of universal fault-tolerant quantum computation on DFSs.

PMID- 12005608
TI  - Instability and spatiotemporal dynamics of alternans in paced cardiac tissue.
AB  - We derive an equation that governs the spatiotemporal dynamics of small amplitude
      alternans in paced cardiac tissue. We show that a pattern-forming linear
      instability leads to the spontaneous formation of stationary or traveling waves
      whose nodes divide the tissue into regions with opposite phase of oscillation of
      action potential duration. This instability is important because it creates
      dynamically a heterogeneous electrical substrate for the formation of conduction
      blocks and the induction of fibrillation if the tissue size exceeds a fraction of
      the pattern wavelength. We derive an analytical expression for this wavelength as
      a function of three basic length scales related to dispersion and intercellular
      electrical coupling.

PMID- 12005609
TI  - High-resolution small-angle x-ray diffraction study of long-range order in hard
      sphere colloidal crystals.
AB  - The long-range order parameters in single crystals of hard colloidal spheres
      grown in sediments of colloid-polymer mixtures are determined using synchrotron
      small-angle x-ray diffraction with a resolution of 10(-6) of the wave vector. The
      interplanar positional order derived from the width of lattice reflections
      extends over at least 500 lattice planes. The lattice planes are orientationally
      correlated within approximately 0.1 degrees throughout the crystals, whereas the
      stacking of hexagonal planes remains random.

PMID- 12005610
TI  - Soret effect in interacting micellar solutions.
AB  - We show that electrostatic effects have a dramatic influence on thermal diffusion
      of charged micelles. In the dilute regime, the Soret coefficient strongly
      decreases with the solution ionic strength, and scales as the square of the Debye
      Huckel length. Yet, collective effects yield a reversed scenario even at fairly
      low surfactant concentration. We find that single-particle behavior can be
      explained using an interfacial tension mechanism proposed by Ruckenstein, which
      also fairly accounts for collective effects and opens the way to a general
      picture of thermal diffusion in disperse systems.

PMID- 12005611
TI  - Spatial resonances and superposition patterns in a reaction-diffusion model with
      interacting Turing modes.
AB  - Spatial resonances leading to superlattice hexagonal patterns, known as "black
      eyes," and superposition patterns combining stripes and/or spots are studied in a
      reaction-diffusion model of two interacting Turing modes with different
      wavelengths. A three-phase oscillatory interlacing hexagonal lattice pattern is
      also found, and its appearance is attributed to resonance between a Turing mode
      and its subharmonic.

PMID- 12005612
TI  - Comment on "Nucleation and interfacial coupling between pure and dirty superfluid
      phases of 3He".

PMID- 12005616
TI  - Comment on "Prediction of electronic excited states of adsorbates on metal
      surfaces from first principles".

PMID- 12005614
TI  - Comment on "Strain-induced nonanalytic short-range order in the spin glass
      Cu83Mn17".

PMID- 12005618
TI  - Shell structure and pairing for interacting fermions in a trap.
AB  - The shell structures for weakly interacting fermions in harmonic oscillator traps
      at zero temperature undergo several transitions depending on the number of
      particles in the trap and their interaction strength. Calculations of the one and
      two-particle spectra give the pairing gaps, and the many particle state is
      constructed by the seniority scheme. For sufficiently few particles, N less than
      or similar to 10(4), the pairing field exceeds the mean-field splitting of single
      particle levels at the Fermi surface and the greater number of almost degenerate
      states due to the SU(3) symmetry in the harmonic oscillator shell lead to
      supergaps. Deformation and rotation are also discussed.

PMID- 12005619
TI  - Size of two-body weakly bound objects: short versus long range potentials.
AB  - The variation of the size of two-body objects is investigated, as the separation
      energy approaches zero, with both long range potentials and short range
      potentials having a repulsive core. It is shown that long range potentials can
      also give rise to very extended systems. Except for the l = 0 state, the
      asymptotic laws differ according to the range of the potential. For short range
      potentials defined by two and three parameters, their sensitivity to the shape
      and length is studied. These ideas as well as the transition from the short to
      the long range regime for the l = 0 case are illustrated using the Kratzer
      potential.

PMID- 12005620
TI  - Lorentz invariance with an invariant energy scale.
AB  - We propose a modification of special relativity in which a physical energy, which
      may be the Planck energy, joins the speed of light as an invariant, in spite of a
      complete relativity of inertial frames and agreement with Einstein's theory at
      low energies. This is accomplished by a nonlinear modification of the action of
      the Lorentz group on momentum space, generated by adding a dilatation to each
      boost in such a way that the Planck energy remains invariant. The associated
      algebra has unmodified structure constants. We also discuss the resulting
      modifications of field theory and suggest a modification of the equivalence
      principle which determines how the new theory is embedded in general relativity.

PMID- 12005621
TI  - Brownian motion exhibiting absolute negative mobility.
AB  - We consider a single Brownian particle in a spatially symmetric, periodic system
      far from thermal equilibrium. This setup can be readily realized experimentally.
      Upon application of an external static force F, the average particle velocity is
      negative for F>0 and positive for F<0 (absolute negative mobility).

PMID- 12005622
TI  - Conformal invariance of the Ising model in three dimensions.
AB  - We investigate a critical Ising-like model in the curved geometry S2 x R1
      obtained by a conformal mapping of the infinite 3D space R3. The incompatibility
      of regular lattices with this geometry is avoided by use of the anisotropic limit
      of the lattice Ising model, which renders one of the space coordinates
      continuous. We determine magnetic and energylike correlation lengths of this
      model by means of a cluster Monte Carlo algorithm. From these data, and the
      assumption of conformal invariance, we obtain the magnetic and temperature
      scaling dimensions as X(h) = 0.5178(12) and X(t) = 1.423(19), respectively. These
      numbers are in a good agreement with the existing results for the 3D Ising
      universality class.

PMID- 12005623
TI  - Dark matter spikes and annihilation radiation from the galactic center.
AB  - The annihilation rate of weakly interacting cold dark matter particles at the
      galactic center could be greatly enhanced by the growth of a density spike around
      the central supermassive black hole (SBH). Here we discuss the effects of
      hierarchical mergers on the central spike. Mergers between halos containing SBHs
      lead to the formation of SBH binaries which transfer energy to the dark matter
      particles, lowering their density. The predicted flux of annihilation photons
      from the galactic center is several orders of magnitude smaller than in models
      that ignore the effects of SBHs and mergers. Measurement of the annihilation
      radiation could in principle be used to constrain the merger history of the
      galaxy.

PMID- 12005625
TI  - Exclusive measurement of the pp --> pppi(+)pi(-) reaction near threshold.
AB  - The pp-->pp pi(+) pi(-) reaction has been measured exclusively near threshold at
      CELSIUS. The total cross sections are nearly an order of magnitude lower than
      expected from previous inclusive measurements. The differential cross sections
      reveal pp-->pp(*)(1440)-->pp sigma = pp(pi(+)pi(-))(I = l = 0) as the dominant
      process as well as significant contributions from p(*)-->Delta(++)pi(-)-->psigma.
      The observed anisotropy in the proton angular dependence is consistent with heavy
      meson exchange. In the invariant mass spectra, no narrow structures of
      statistical relevance (3sigma) are found.

PMID- 12005628
TI  - Probing the high density behavior of the nuclear symmetry energy with high energy
      heavy-ion collisions.
AB  - High energy heavy-ion collisions are proposed as a novel means to constrain
      stringently the high density (HD) behavior of nuclear symmetry energy. Within an
      isospin-dependent hadronic transport model, it is shown for the first time that
      the isospin asymmetry of the HD nuclear matter formed in high energy heavy-ion
      collisions is uniquely determined by the HD behavior of the nuclear symmetry
      energy. Experimental signatures in two sensitive probes, i.e., pi(-) to pi(+)
      ratio and neutron-proton differential collective flow, are also investigated.

PMID- 12005629
TI  - Threshold-related enhancement of the high-energy plateau in above-threshold
      detachment.
AB  - We present nonperturbative theoretical results showing a resonant-like
      enhancement of above-threshold detachment spectra in the region of the high
      energy plateau as the laser intensity sweeps across channel thresholds. This
      enhancement has a pure quantum origin stemming from well-known threshold
      phenomena in multichannel problems whose features are clearly demonstrated in our
      numerical results. Similar well-known anomalies at neutral atom thresholds are
      expected to explain experimentally observed resonant-like enhancements of above
      threshold ionization spectra.

PMID- 12005624
TI  - Search for leptoquark pairs decaying into nunu+jets in pp collisions at square
      root[s] = 1.8 TeV.
AB  - We present the results of a search for leptoquark (LQ) pairs in (85.2+/-3.7) pb(
      1) of pp* collider data collected by the D0 experiment at the Fermilab Tevatron.
      We observe no evidence for leptoquark production and set a limit on sigma(pp*-
      >LQLQ-->nunu+jets) as a function of the mass of the leptoquark (m(LQ)). Assuming
      the decay LQ-->nuq, we exclude scalar leptoquarks for m(LQ) < 98 GeV/c(2), and
      vector leptoquarks for m(LQ) < 200 GeV/c(2) and coupling which produces the
      minimum cross section, at a 95% confidence level.

PMID- 12005630
TI  - 4sigma(-1) inner valence photoionization dynamics of NO derived from
      photoelectron-photoion angular correlations.
AB  - A complete description of the 4sigma photoionization dynamics of NO has been
      derived from angle resolved photoelectron-photoion-coincidence experiments. The
      combination of measurements performed with linearly and circularly polarized
      light has made it possible to obtain a unique set of complex dipole matrix
      elements. A comparison with multichannel-Schwinger-configuration-interaction
      calculations shows good agreement in the general shapes of the angular
      distributions due to the correct description of the main components and phase
      differences. Still, many transition moments agree only qualitatively.

PMID- 12005631
TI  - Antiproton stopping at low energies: confirmation of velocity-proportional
      stopping power.
AB  - The stopping power for antiprotons in various solid targets has been measured in
      the low-energy range of 1-100 keV. In agreement with most models, in particular
      free-electron gas models, the stopping power is found to be proportional to the
      projectile velocity below the stopping-power maximum. Although a stopping power
      proportional to velocity has also been observed for protons, the interpretation
      of such measurements is difficult due to the presence of charge exchange
      processes. Hence, the present measurements constitute the first unambiguous
      support for a velocity-proportional stopping power due to target excitations by a
      pointlike projectile.

PMID- 12005632
TI  - Time-frequency characterization of femtosecond extreme ultraviolet pulses.
AB  - We present energy-resolved cross-correlation measurements of an extreme
      ultraviolet (XUV) pulse, generated as the fifth harmonic (15.5 eV) of an intense
      80 fs laser pulse centered at 400 nm. Spectrally resolving the cross-correlation
      signal allows us to characterize the time-dependent frequency of the XUV pulse.
      We find that the fifth harmonic has a small negative chirp in excess of that
      predicted by perturbation theory. In addition, by manipulating the chirp of the
      driving laser we can induce and measure a positive or a negative chirp on the XUV
      pulse.

PMID- 12005626
TI  - Transverse-mass dependence of two-pion correlations in Au+Au collisions at square
      root[s(NN)] = 130 GeV.
AB  - Two-pion correlations in square root[s(NN)] = 130 GeV Au+Au collisions at RHIC
      have been measured over a broad range of pair transverse momentum k(T) by the
      PHENIX experiment at RHIC. The k(T) dependent transverse radii are similar to
      results from heavy-ion collisions at square root[s(NN)] = 4.1, 4.9, and 17.3 GeV,
      whereas the longitudinal radius increases monotonically with beam energy. The
      ratio of the outwards to sidewards transverse radii (R(out)/R(side)) is
      consistent with unity and independent of k(T).

PMID- 12005633
TI  - Measurement of the intensity-dependent atomic dipole phase of a high harmonic by
      frequency-resolved optical gating.
AB  - The temporal profile and phase of the fifth harmonic of a Ti:sapphire laser were
      fully characterized by two-photon ionization frequency-resolved optical gating
      technique for the first time. The fifth harmonic was found to have negative chirp
      and the pulse compression was demonstrated. The negative chirp is well explained
      by using a zero-range potential model. This technique is scalable to extreme
      ultraviolet (XUV) and soft x-ray regions by using currently available light
      sources, making it possible to measure the pulse duration and phase of vacuum
      ultraviolet, XUV, and soft x-ray pulses.

PMID- 12005627
TI  - Measurement of single electrons and implications for charm production in Au+Au
      collisions at square root[s(NN)] = 130 GeV.
AB  - Transverse momentum spectra of electrons from Au+Au collisions at square
      root[s(NN)] = 130 GeV have been measured at midrapidity by the PHENIX experiment
      at the Relativistic Heavy Ion Collider. The spectra show an excess above the
      background from photon conversions and light hadron decays. The electron signal
      is consistent with that expected from semileptonic decays of charm. The yield of
      the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025+/-0.004(stat)+/
      0.010(syst) in central collisions, and the corresponding charm cross section is
      380+/-60(stat)+/-200(syst) microb per binary nucleon-nucleon collision.

PMID- 12005634
TI  - Thickness fluctuations in turbulent soap films.
AB  - Rapidly flowing soap films provide a simple and attractive system to study two
      dimensional hydrodynamics and turbulence. By measuring the rapid fluctuations of
      the thickness of the film in the turbulent regime, we find that the statistics of
      these fluctuations closely resemble those of a passive scalar field in a
      turbulent flow. The scalar spectra are well described by Kolmogorov-like scaling
      while the high-order moments show clear deviations from regular scaling just like
      dye or temperature fluctuations in 3D turbulent flows.

PMID- 12005635
TI  - Segregation in binary mixtures under gravity.
AB  - We employ kinetic theory for a binary mixture to study segregation by size and/or
      mass in a gravitational field. Simple segregation criteria are obtained for
      spheres and disks that are supported by numerical simulations.

PMID- 12005636
TI  - Reaction and concentration dependent diffusion model.
AB  - We study the formation of patterns in the genuinely nonlinear reaction diffusion
      model equation u(t)+2a(u(2))(x) = (u(2))(xx)+F(x,u), where u may be viewed as an
      amplitude of a thermal wave in plasma or density of a biological species and F =
      u(1-u) or F = q(x)u(l), l = 0,2. We provide a transformation which maps the model
      into a purely diffusive process free of its interacting part and its intrinsic
      temporal and spatial scales. The well known attractors of the diffusive process
      enable us to completely characterize the emerging patterns which, depending on F
      and initialization, may be a semicompact, or a compact, traveling wave or a
      nontrivial equilibrium.

PMID- 12005638
TI  - Particle interaction measurements in a Coulomb crystal using caged-particle
      motion.
AB  - A technique for characterizing the particle interaction potential of a Coulomb
      crystal is developed. The mean-square displacement (MSD) is measured, showing
      both caged- and superdiffusive-particle motions. By subtracting the center of
      mass of neighboring particles in computing MSD, only short-wavelength particle
      motions are retained. This yields the lattice Einstein frequency, which contains
      information about the interparticle forces and potentials. Video measurements of
      particle motions in a complex (dusty) plasma are used to demonstrate the
      technique.

PMID- 12005637
TI  - Extremely low vertical-emittance beam in the accelerator test facility at KEK.
AB  - Electron beams with the lowest, normalized transverse emittance recorded so far
      were produced and confirmed in single-bunch-mode operation of the Accelerator
      Test Facility at KEK. We established a tuning method of the damping ring which
      achieves a small vertical dispersion and small x-y orbit coupling. The vertical
      emittance was less than 1% of the horizontal emittance. At the zero-intensity
      limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam
      energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were
      observed, which had been expected in view of the extremely high particle density
      due to the small transverse emittance.

PMID- 12005639
TI  - RF absorption and ion heating in helicon sources.
AB  - Experimental data are presented that are consistent with the hypothesis that
      anomalous rf absorption in helicon sources is due to electron scattering arising
      from parametrically driven ion-acoustic waves downstream from the antenna. Also
      presented are ion temperature measurements demonstrating anisotropic heating (T(
      perpendicular)>T(parallel)) at the edge of the discharge. The most likely
      explanation is ion-Landau damping of electrostatic slow waves at a local lower
      hybrid-frequency resonance.

PMID- 12005640
TI  - Reduction of the coherence time of an intense laser pulse propagating through a
      plasma.
AB  - We present direct measurements of the coherence time of a laser beam after
      propagation through an underdense plasma. At an intensity of 10(14) W/cm(2), a
      large decrease of the coherence time is observed, from 300 ps to a few
      picoseconds. This decrease is larger as the plasma density is increased or as the
      light is scattered at larger angles. The amount of temporal decorrelation as well
      as the effect of the plasma density, laser intensity, and scattering angle all
      coincide with trends observed in recent numerical simulations.

PMID- 12005641
TI  - Size scaling of turbulent transport in magnetically confined plasmas.
AB  - Transport scaling with respect to device size in magnetically confined plasmas is
      critically examined for electrostatic ion-temperature-gradient turbulence using
      global gyrokinetic particle simulations. It is found, by varying device size
      normalized by ion gyroradius while keeping other dimensionless plasma parameters
      fixed, that fluctuation scale length is microscopic in the presence of zonal
      flows. The local transport coefficient exhibits a gradual transition from a Bohm
      like scaling for device sizes corresponding to present-day experiments to a gyro
      Bohm scaling for future larger devices.

PMID- 12005642
TI  - Fractal properties of trivelpiece-gould waves in periodic plasma-filled
      waveguides.
AB  - It is shown that dispersion curves describing a spectrum of Trivelpiece-Gould
      (TG) waves in periodic plasma-filled waveguides have a fractal nature. They are
      not solid lines as for other types of waves in periodic waveguides but suffer
      from discontinuities of the first kind at any k(z) = (P/Q) (2m+1)pi/d, where P
      and Q are integers, d is the period of the corrugation, and m is the transverse
      index of a mode. The gaps correspond to forbidden bands. The evaluation of the
      Hausdorf dimension of the dispersion curves is presented. Finally, qualitative
      consequences of the fractal nature of TG waves for plasma microwave electronics
      are discussed.

PMID- 12005643
TI  - Observation of a new excitation in bcc 4He by inelastic neutron scattering.
AB  - We report neutron-scattering measurements of the phonons in bcc solid 4He. In
      general, only three acoustic phonon branches should exist in a monatomic cubic
      crystal. In addition to these phonon branches, we found a new "opticlike" mode
      along the [110] direction. One possible interpretation of this new mode is in
      terms of localized excitations unique to a quantum solid.

PMID- 12005644
TI  - Slater ice rules and H-bond dynamics in KDP-type systems.
AB  - We report on the first observation of the dynamics of correlated hydrogen
      switching among the six Slater D2PO4 configurations, induced by unpaired D3PO4
      and DPO4 Takagi group diffusion in a deuteron glass Rb0.5(ND4)0.5D2PO4. The
      results obtained by two-dimensional (2D) 31P exchange NMR prove the validity of
      the Slater-Takagi ice rules and allow for the direct determination of the
      correlation time for the unpaired Takagi group visits to a given D2PO4 group.

PMID- 12005645
TI  - Interplay between time-temperature transformation and the liquid-liquid phase
      transition in water.
AB  - We study the new water model proposed by Mahoney and Jorgensen [J. Chem. Phys.
      112, 8910 (2000)], which is closer to real water than previously proposed
      classical pairwise additive potentials. We simulate the model in a wide range of
      deeply supercooled states and find (i) the existence of a nonmonotonic "nose
      shaped" temperature of maximum density line and a nonreentrant spinodal, (ii) the
      presence of a low-temperature phase transition, (iii) the free evolution of bulk
      water to ice, and (iv) the time-temperature-transformation curves at different
      densities.

PMID- 12005646
TI  - Dewetting of thin polymer films near the glass transition.
AB  - Dewetting of ultrathin polymer films near the glass transition exhibits
      unexpected front morphologies [G. Reiter, Phys. Rev. Lett. 87, 186101 (2001)].
      Here, we present the first theoretical attempt to understand these features,
      focusing on the shear-thinning behavior of these films. We analyze the profile of
      the dewetting film, and characterize the time evolution of the dry region radius,
      R(d)(t), and of the rim height, h(m)(t). After a transient time, depending on the
      initial thickness, h(m)(t) grows like square root[t] while R(d)(t) increases like
      exp(square root[t]). Different regimes of growth are expected, depending on the
      initial film thickness and experimental time range.

PMID- 12005647
TI  - Core level photoemission evidence of frustrated surface molecules: a germ of
      disorder at the (111) surface of C60 before the order-disorder surface phase
      transition.
AB  - Using high resolution core level photoemission, we investigated the disordering
      transition of the fullerene molecules at the (111) surface of C (60) films. The
      experimental evidence of a two-step mechanism for the rotational disordering of
      surface fullerene molecules is provided. The data are consistent with a recent
      model in which the rotational degrees of freedom of one molecule, out of the four
      inequivalent C (60) molecules of the low temperature (2x2) surface unit cell,
      melt about 100 K before the bulk phase transition.

PMID- 12005648
TI  - Instability driven fragmentation of nanoscale fractal islands.
AB  - Formation and evolution of fragmentation instabilities in fractal islands,
      obtained by deposition of silver clusters on graphite, are studied. The
      fragmentation dynamics and subsequent relaxation to the equilibrium shapes are
      controlled by the deposition conditions and cluster composition. Sharing common
      features with other materials' breakup phenomena, the fragmentation instability
      is governed by the length-to-width ratio of the fractal arms.

PMID- 12005649
TI  - Reversible structural transition in epitaxial manganite film.
AB  - A reversible structural transition of an epitaxial La(2/3)Sr(1/3)MnO3 film
      deposited on a LaAlO3 substrate has been investigated by means of in situ high
      resolution transmission electron microscopy and electron diffraction, combined
      with image and diffraction calculations. We observe that the crystallographic
      symmetry of the film can be lowered via electron beam irradiation, leading to a
      rhombohedral-monoclinic transition. This transition can be attributed to the
      cooperating effect of the mismatch stress and the irradiation-induced thermal
      stress.

PMID- 12005650
TI  - Surface stress anisotropy of Ge(001).
AB  - By analyzing the equilibrium shape of vacancy islands on the Ge(001) surface we
      have determined the surface stress anisotropy, i.e., the difference between the
      compressive stress component along the substrate dimer rows and the tensile
      stress component perpendicular to the substrate dimer rows. In order to extract
      the surface stress anisotropy we have used a model recently put forward by Li et
      al. [Phys. Rev. Lett. 85, 1922 (2000)]. The surface stress anisotropy of the
      clean Ge(001) surface is found to be 80+/-30 meV/A(2). This value is comparable
      to the surface stress anisotropy of the closely related Si(001) surface.

PMID- 12005651
TI  - Adsorbate-induced pinning of a charge-density wave in a quasi-1D metallic chains:
      Na on the In/Si(111)-(4x1) surface.
AB  - We find that foreign adsorbates acting as local impurities can induce a metal
      insulator transition by pinning a charge-density wave (CDW) on the quasi-1D
      metallic In/Si(111)-(4x1) chain system. Our scanning tunneling microscopy image
      clearly reveals the presence of a new local 4x2 structure nucleated by Na adatoms
      at room temperature, which turns out to be insulating with a doubled periodicity
      along the chains. We directly determine a CDW gap energy Delta = 105+/-8 meV by
      identifying a characteristic loss peak in our high-resolution electron-energy
      loss spectra. We thus report the first observation of a local impurity-derived
      Peierls-like reconstruction of a quasi-1D system.

PMID- 12005652
TI  - Local simulation algorithms for Coulomb interactions.
AB  - Long ranged electrostatic interactions are time consuming to calculate in
      molecular dynamics and Monte Carlo simulations. We introduce an algorithmic
      framework for simulating charged particles which modifies the dynamics so as to
      allow equilibration using a local Hamiltonian. The method introduces an auxiliary
      field with constrained dynamics so that the equilibrium distribution is
      determined by the Coulomb interaction. We demonstrate the efficiency of the
      method by simulating a simple, charged lattice gas.

PMID- 12005653
TI  - New spectroscopy solves an old puzzle: the Kondo scale in heavy fermions.
AB  - Resonant inelastic x-ray scattering (RIXS) yields clear evidence of spectroscopic
      Kondo scales in heavy fermions. In YbInCu4 and YbAgCu4 RIXS probes the Yb2+
      component of the hybrid ground state and the temperature dependence of the Yb 4f
      occupation. We report a sudden valence change at a phase transition in YbInCu4,
      but a continuous temperature dependence in YbAgCu4, consistent with the
      predictions of the Anderson impurity model, for a Kondo temperature T(K) = 70 K.
      These results solve a long-standing controversy and establish RIXS as a
      quantitative probe of the electronic structure of strongly correlated electron
      systems.

PMID- 12005654
TI  - Low-density spin susceptibility and effective mass of mobile electrons in Si
      inversion layers.
AB  - We studied the Shubnikov-de Haas (SdH) oscillations in high-mobility Si-MOS
      samples over a wide range of carrier densities n approximately (1-50)x10(11) cm(
      2), which includes the vicinity of the apparent metal-insulator transition in two
      dimensions (2D MIT). Using a novel technique of measuring the SdH oscillations in
      superimposed and independently controlled parallel and perpendicular magnetic
      fields, we determined the spin susceptibility chi(*), the effective mass m(*),
      and the g(*) factor for mobile electrons. These quantities increase gradually
      with decreasing density; near the 2D MIT, we observed enhancement of chi(*) by a
      factor of approximately 4.7.

PMID- 12005655
TI  - Spatial decay of the single-particle density matrix in insulators: analytic
      results in two and three dimensions.
AB  - Analytic results for the asymptotic decay of the electron density matrix in
      insulators have been obtained in all three dimensions (D = 1,2,3) for a tight
      binding model defined on a simple cubic lattice. The anisotropic decay length is
      shown to be dependent on the energy parameters of the model. The existence of the
      power-law prefactor, proportional, variant r(-D/2), is demonstrated.

PMID- 12005656
TI  - Spin polarization of CrO2 at and across an artificial barrier.
AB  - We report a systematic study of the spin polarization of epitaxial CrO2 films at
      and across an interface using planar junctions with a superconducting
      counterelectrode. By chemical modification of the CrO2 surface before the
      deposition of the superconductor, junctions with a wide range of barrier strength
      were obtained. Analysis of the conductance data on these junctions, especially
      under Zeeman splitting of the superconducting density of states, yields
      consistent, close to full spin polarization for CrO2 regardless of the barrier
      strength.

PMID- 12005657
TI  - Circuit theory for full counting statistics in multiterminal circuits.
AB  - We propose a theory that treats the current, noise, and, generally, the full
      current statistics of electron transfer in a mesoscopic system in a unified,
      simple, and efficient way. The theory appears to be a circuit theory of 2 x 2
      matrices associated with Keldysh Green functions. We illustrate the theory by
      considering the big fluctuations of currents in various three-terminal circuits.

PMID- 12005658
TI  - Full counting statistics of a superconducting beam splitter.
AB  - We study the statistics of charge transport in a mesoscopic three-terminal device
      with one superconducting terminal and two normal-metal terminals. We calculate
      the full distribution of transmitted charges into the two symmetrically biased
      normal terminals. In a wide parameter range, we find large positive cross
      correlations between the currents in the two normal arms. We also determine the
      third cumulant that provides additional information on the statistics not
      contained in the current noise.

PMID- 12005659
TI  - Incommensurate magnetic ordering in Sr2Ru(1-x)TixO4.
AB  - In Sr2RuO4 the spin excitation spectrum is dominated by incommensurate
      fluctuations at q = (0.3 0.3q(z)), which arise from Fermi-surface nesting. We
      show that upon Ti substitution, known to suppress superconductivity, a short
      range magnetic order develops with a propagation vector (0.307 0.307 1). In
      Sr2Ru0.91Ti0.09O4, the ordered moment points along the c direction. This finding
      shows that superconducting Sr2RuO4 is extremely close to an incommensurate spin
      density wave instability.

PMID- 12005660
TI  - Origin of charge-orbital order in the half-doped manganites.
AB  - The microscopic origin of the charge and orbital order in the half-doped
      manganites is examined from ab initio density-functional calculations and exact
      diagonalization studies. It is shown that the dominant mechanism responsible for
      the charge order is the Jahn-Teller coupling, with a lesser but significant
      contribution from the on-site Coulomb interaction. The band structure shows a
      sizable interchain coupling between the zigzag chains, leading to a considerable
      band dispersion normal to the chains, in sharp contrast with the zigzag chain
      physics.

PMID- 12005661
TI  - Hysteresis in the random-field Ising model and bootstrap percolation.
AB  - We study hysteresis in the random-field Ising model with an asymmetric
      distribution of quenched fields, in the limit of low disorder in two and three
      dimensions. We relate the spin flip process to bootstrap percolation, and show
      that the characteristic length for self-averaging L small star, filled increases
      as exp[exp(J/Delta)] in 2D, and as exp(exp[exp(J/Delta)]) in 3D, for disorder
      strength Delta much less than the exchange coupling J. For system size 1<<L<L
      small star, filled, the coercive field h(coer) varies as 2J-DeltalnlnL for the
      square lattice, and as 2J-DeltalnlnlnL on the cubic lattice. Its limiting value
      is 0 for L-->infinity for both square and cubic lattices. For lattices with
      coordination number 3, the limiting magnetization shows no jump, and h(coer)
      tends to J.

PMID- 12005662
TI  - Colossal magnetoresistance is a Griffiths singularity.
AB  - It is now widely accepted that the magnetic transition in doped manganites that
      show large magnetoresistance is a type of percolation effect. This paper
      demonstrates that the transition should be viewed in the context of the Griffiths
      phase that arises when disorder suppresses a magnetic transition. This approach
      explains unusual aspects of susceptibility and heat capacity data from a single
      crystal of La0.7Ca0.3MnO3.

PMID- 12005663
TI  - Conjugation-length dependence of spin-dependent exciton formation rates in pi
      conjugated oligomers and polymers.
AB  - We have measured the ratio, r = sigma(S)/sigma(T) of the formation cross section,
      sigma of singlet and triplet excitons from polarons in pi-conjugated oligomer and
      polymer films, using a spectroscopic technique we developed recently. We
      discovered a universal relation between r and the conjugation length (CL): r(-1)
      depends linearly on CL-1, irrespective of the chain structure. Since r is
      directly related to the maximum possible electroluminescence quantum efficiency
      in organic light emitting diodes (OLED), our results indicate that polymers have
      an advantage over small molecules in OLED applications.

PMID- 12005664
TI  - Blackbody spectra for sonoluminescing hydrogen bubbles.
AB  - The dynamical motion of sonoluminescing bubbles formed from a mixture of water
      and hydrogen gas indicates that these bubbles contain hydrogen. Their spectrum is
      well matched by an ideal 6000 K blackbody radiating from a surface with a radius
      less than 1/4 microm. According to this model, the state of matter inside the
      collapsed bubble is so stressed that the photon mean free path is much smaller
      than 1 microm. Implications for various theories of the light-emitting mechanism
      and the role of chemical reactions are discussed.

PMID- 12005665
TI  - Entangled light from white noise.
AB  - An atom that couples to two distinct leaky optical cavities is driven by an
      external optical white noise field. We describe how entanglement between the
      light fields sustained by two optical cavities arises in such a situation. The
      entanglement is maximized for intermediate values of the cavity damping rates and
      the intensity of the white noise field, vanishing both for small and for large
      values of these parameters and thus exhibiting a stochastic-resonancelike
      behavior. This example illustrates the possibility of generating entanglement by
      exclusively incoherent means and sheds new light on the constructive role noise
      may play in certain tasks of interest for quantum information processing.

PMID- 12005666
TI  - Roles of stiffness and excluded volume in DNA denaturation.
AB  - The nature and the universal properties of DNA thermal denaturation are
      investigated by Monte Carlo simulations. For suitable lattice models we determine
      the exponent c describing the decay of the probability distribution of
      denaturated loops of length l, P approximately l(-c). If excluded volume effects
      are fully taken into account, c = 2.10(4) is consistent with a first order
      transition. The stiffness of the double stranded chain has the effect of
      sharpening the transition, if it is continuous, but not of changing its order and
      the value of the exponent c, which is also robust with respect to inclusion of
      specific base-pair sequence heterogeneities.

PMID- 12005667
TI  - Experimental control of cardiac muscle alternans.
AB  - We demonstrate that alternans in small pieces of in vitro paced bullfrog (Rana
      Catesbeiana) myocardium can be suppressed by making minute adjustments to the
      pacing period in response to real time measurements of the action potential
      duration. Control is possible over a large range of physiological conditions over
      many animals and the self-referencing control protocol can automatically adjust
      to changes in the pacing interval. Our results suggest the feasibility of
      developing low-energy methods for maintaining normal cardiac function.

PMID- 12005668
TI  - Breakdown of energy equipartition in a 2D binary vibrated granular gas.
AB  - We report experiments on the equipartition of kinetic energy in a mixture of
      pairs of different types of grains vibrated in two dimensions. In general, the
      two types of grains do not attain the same granular temperature, T(g) =
      1/2m<v(2)>. However, the temperature ratio is constant in the bulk of the system
      and independent of the vibration velocity. The ratio depends strongly on the
      ratio of mass densities of the grains, but not on their inelasticity. Also, the
      temperature ratio is insensitive to compositional variables such as the number
      fraction of each component and the total number density. We conclude that a
      single granular temperature, as traditionally defined, does not characterize a
      multicomponent mixture.

PMID- 12005669
TI  - Particle number fractionalization of an atomic Fermi-Dirac gas in an optical
      lattice.
AB  - We show that a dilute two-species gas of Fermi-Dirac alkali-metal atoms in a
      periodic optical lattice may exhibit fractionalization of the particle number
      when the two components are coupled via a coherent electromagnetic field with a
      topologically nontrivial phase profile. This results in fractional eigenvalues of
      the spin operator with vanishing fluctuations. The fractional part can be
      accurately controlled by modifying the effective detuning of the electromagnetic
      field.

PMID- 12005670
TI  - Quadrupole collective modes in trapped finite-temperature Bose-Einstein
      condensates.
AB  - Finite-temperature simulations are used to study quadrupole excitations of a
      trapped Bose-Einstein condensate. We focus specifically on the m = 0 mode, where
      a long-standing theoretical problem is to account for an anomalous variation of
      the mode frequency with temperature. We explain this behavior in terms of the
      excitation of two separate modes, corresponding to the coupled motion of the
      condensate and the thermal cloud. The relative amplitude of the modes depends
      sensitively on the temperature and on the frequency of the harmonic drive used to
      excite them. Good agreement with experiment is found for appropriate drive
      frequencies.

PMID- 12005671
TI  - Two-component Bose-Einstein condensates with a large number of vortices.
AB  - We consider the condensate wave function of a rapidly rotating two-component Bose
      gas with an equal number of particles in each component. If the interactions
      between like and unlike species are very similar (as occurs for two hyperfine
      states of (87)Rb or (23)Na) we find that the two components contain identical
      rectangular vortex lattices, where the unit cell has an aspect ratio of sqrt[3],
      and one lattice is displaced to the center of the unit cell of the other. Our
      results are based on an exact evaluation of the vortex lattice energy in the
      large angular momentum (or quantum Hall) regime.

PMID- 12005672
TI  - Macroscopic dynamics of a trapped Bose-Einstein condensate in the presence of 1D
      and 2D optical lattices.
AB  - The hydrodynamic equations of superfluids for a weakly interacting Bose gas are
      generalized to include the effects of periodic optical potentials produced by
      stationary laser beams. The new equations are characterized by a renormalized
      interaction coupling constant and by an effective mass accounting for the inertia
      of the system along the laser direction. For large laser intensities the
      effective mass is directly related to the tunneling rate between two consecutive
      wells. The predictions for the frequencies of the collective modes of a
      condensate confined by a magnetic harmonic trap are discussed for both 1D and 2D
      optical lattices and compared with recent experimental data.

PMID- 12005673
TI  - Conservation laws for collisions of branes and shells in general relativity.
AB  - We consider the collision of self-gravitating n-branes in a (n+2)-dimensional
      spacetime. We show that there is a geometrical constraint which can be expressed
      as a simple sum rule for angles characterizing Lorentz boosts between branes and
      the intervening spacetime regions. This constraint can then be reinterpreted as
      either energy or momentum conservation at the collision.

PMID- 12005675
TI  - Ghost fields in classical gauge theories.
AB  - It is shown that ghost fields, characterized as unphysical entities, are a
      valuable tool in finding numerical solutions of the Euler-Lagrange equations of
      gauge field theories.

PMID- 12005674
TI  - Measurement of the K(L) charge asymmetry.
AB  - We present a measurement of the charge asymmetry delta(L) in the mode K(L)-
      >pi(+/-)e(-/+)nu based on 298 x 10(6) analyzed decays. We measure a value of
      delta(L) = [3322+/-58(stat)+/-47(syst)]x10(-6), in good agreement with previous
      measurements and 2.4 times more precise than the current best published result.
      The result is used to place more stringent limits on CPT and DeltaS = DeltaQ
      violation in the neutral kaon system.

PMID- 12005676
TI  - Vector-meson-dominance model for radiative decays involving light scalar mesons.
AB  - We study a vector-dominance model which predicts quite a large number of
      currently interesting decay amplitudes of the types S-->gammagamma, V-->Sgamma,
      and S-->Vgamma, where S and V denote scalar and vector mesons, in terms of three
      parameters. As an application, the model makes it easy to study in detail a
      recent proposal to boost the ratio Gamma(phi-->f(0)gamma)/Gamma(phi-
      >a(0)(0)gamma) by including the isospin violating a(0)(0)-f(0) mixing. However,
      we find that this effect is actually small in our model.

PMID- 12005677
TI  - Discovering new physics in the decays of black holes.
AB  - If the scale of quantum gravity is near a TeV, the CERN Large Hadron Collider
      (LHC) will be producing one black hole (BH) about every second, thus qualifying
      as a BH factory. With the Hawking temperature of a few hundred GeV, these rapidly
      evaporating BHs may produce new, undiscovered particles with masses approximately
      100 GeV. The probability of producing a heavy particle in the decay depends on
      its mass only weakly, in contrast with the exponentially suppressed direct
      production. Furthermore, backgrounds in the BH sample can be made small. Using
      the Higgs boson as an example, we show that it may be found at the LHC on the
      first day of its operation, even with incomplete detectors.

PMID- 12005678
TI  - Invisible charginos and neutralinos from gauge boson fusion: a way to explore
      anomaly mediation.
AB  - We point out that vector boson fusion at the Large Hadron Collider (LHC) can lead
      to useful signals for charginos and neutralinos in supersymmetric scenarios where
      these particles are almost invisible. The proposed signals are just two forward
      jets with missing transverse energy. It is shown that, in this way, one can put
      by far the strongest constraint on the parameter space of a theory with anomaly
      mediated supersymmetry breaking at the LHC. In addition, scenarios where the
      lightest neutralinos and charginos are Higgsino-like can give signals of the
      above type.

PMID- 12005680
TI  - Resonance transition energies and oscillator strengths in lutetium and
      lawrencium.
AB  - The transition energies and oscillator strengths for nd (2)D(3/2)-(n+1)p
      (2)P(o)(1/2,3/2) transitions in Lu ( n = 5, Z = 71) and Lr ( n = 6, Z = 103) were
      calculated with the multiconfiguration Dirac-Hartree-Fock method. The present
      study confirmed that the ground state of atomic Lr is [Rn]5f(14)7s(2)7p
      (2)P(o)(1/2). The calculation for Lr required wave function expansions of more
      than 330 000 configuration states. In Lu, the transition energies, with Breit and
      QED corrections included, agree with experiment to within 126 cm(-1). In lighter
      elements, core correlation is usually neglected but was found to be of extreme
      importance for these heavy elements, affecting the oscillator strengths by a
      factor of 3 and 2 in Lu and Lr, respectively.

PMID- 12005681
TI  - Entangled two-photon wave packet in a dispersive medium.
AB  - We report an experimental study of group-velocity dispersion effect on an
      entangled two-photon wave packet, generated via spontaneous parametric down
      conversion and propagating through a dispersive medium. Even in the case of using
      cw laser beam for pump, the biphoton wave packet and the second-order correlation
      function spread significantly. The study and understanding of this phenomenon is
      of great importance for quantum information applications, such as quantum
      communication and distant clock synchronization.

PMID- 12005682
TI  - Generating entangled two-photon states with coincident frequencies.
AB  - It is shown that parametric down-conversion, with a short-duration pump pulse and
      a long nonlinear crystal that is appropriately phase matched, can produce a
      frequency-entangled biphoton state whose individual photons are coincident in
      frequency. Quantum interference experiments which distinguish this state from the
      familiar time-coincident biphoton state are described.

PMID- 12005679
TI  - Observation of B(+/-) --> p(-)pK(+/-).
AB  - We report the observation of the decay mode B(+/-) --> p(-)pK(+/-)based on an
      analysis of 29.4 fb(-1) of data collected by the Belle detector at KEKB. This is
      the first example of a b-->s transition with baryons in the final state. The p(
      )p mass spectrum in this decay is inconsistent with phase space and is peaked at
      low mass. The branching fraction for this decay is measured to be B(B+/--->p(
      )pK+/-) = [4.3(+1.1)(-0.9)(stat)+/-0.5(syst)]x 10(-6). We also report upper
      limits for the decays B(0)-->p(-)pK(S) and B(+/-)-->p(-)p pi(+/-).

PMID- 12005683
TI  - Electromagnetic-field distribution measurements in the soft x-ray range: full
      characterization of a soft x-ray laser beam.
AB  - We report direct measurement of the electromagnetic-field spatial distribution in
      a neonlike Ar capillary discharge-driven soft x-ray laser beam. The wave front
      was fully characterized in a single shot using a Shack-Hartmann diffractive
      optics sensor. The wave front was observed to be dependent on the discharge
      pressure and capillary length, as a result of beam refraction variations in the
      capillary plasma. The results predict approximately 70% of the laser beam energy
      can be focused into an area 4 times the size of the diffraction-limited spot,
      reaching intensities of approximately 4 x 10(13) W/cm(2).

PMID- 12005684
TI  - Spectral anomalies at wave-front dislocations.
AB  - In a recent Letter, Gbur, Visser, and Wolf [Phys. Rev. Lett. 88, 013901 (2002)]
      predict that remarkable spectral changes can take place in the neighborhood of
      phase singularities of a diffracted focused wave. We report here the experimental
      observation of this anomalous spectral behavior and show that this is a general
      characteristic of optical vortices. Using a high-resolution interferometric
      technique, we are able to measure directly both the spectral intensity
      distribution and the spectral phase at the singular points of optical waves.

PMID- 12005685
TI  - Role of the intramolecular phase in high-harmonic generation.
AB  - We study numerically the generation of high-order harmonics by two-center
      molecules for arbitrary angles between the molecular axis and the laser
      polarization axis. For fixed angle, the harmonic spectrum exhibits a minimum at a
      frequency which is independent of the laser parameters. The amplitude of each
      harmonic is strongly angle dependent, and a pronounced minimum is found at the
      same angle where a sudden jump in the harmonic phase occurs. By calculating the
      spatial dependence of the harmonic amplitudes and phases, we are able to explain
      these effects in terms of interfering contributions from various regions within
      the molecule.

PMID- 12005686
TI  - Broken symmetries and directed collective energy transport in spatially extended
      systems.
AB  - We study the appearance of directed energy current in homogeneous spatially
      extended systems coupled to a heat bath in the presence of an external ac field
      E(t). The systems are described by nonlinear field equations. By making use of a
      symmetry analysis, we predict the right choice of E(t) and obtain directed energy
      transport for systems with a nonzero topological charge Q. We demonstrate that
      the symmetry properties of motion of topological solitons (kinks and antikinks)
      are equivalent to the ones for the energy current. Numerical simulations confirm
      the predictions of the symmetry analysis and, moreover, show that the directed
      energy current drastically increases as the dissipation parameter alpha reduces.

PMID- 12005687
TI  - Linear theory of ionization cooling in 6D phase space.
AB  - A linear theory is developed for ionization cooling of muon beams in periodic
      channels that can provide cooling of the transverse emittances and also of the
      longitudinal emittance via emittance exchange. The channels incorporate solenoids
      and quadrupoles for transverse focusing, dipoles to generate dispersion, wedged
      absorbers for ionization, and rf cavities for acceleration. The beam evolution
      near equilibrium is described by coupled first-order differential equations for
      five generalized emittances with two excitation sources. The results should be
      useful for understanding the cooling process and for designing cooling channels
      of future muon colliders and neutrino factories.

PMID- 12005688
TI  - Role of parallel flow in the improved mode on the STOR-M tokamak.
AB  - A novel feature of the H-mode induced by compact torus injection on the STOR-M
      tokamak is observed. There is almost no change in the radial electric field
      profiles during and after the L-H transition. The usual hypothesis of the E x B
      shear stabilization mechanism is therefore unlikely to play a role in this
      transition. A new mechanism of the stabilization of microinstabilities by
      parallel flow is suggested as the plausible cause for the transition to this
      improved regime.

PMID- 12005689
TI  - Radiation damping effects on the interaction of ultraintense laser pulses with an
      overdense plasma.
AB  - A strong effect of radiation damping on the interaction of an ultraintense laser
      pulse with an overdense plasma slab is found and studied via a relativistic
      particle-in-cell simulation including ionization. Hot electrons generated by the
      irradiation of a laser pulse with a radiance of I lambda(2)>10(22) W
      microm(2)/cm(2) and duration of 20 fs can convert more than 35% of the laser
      energy to radiation. This incoherent x-ray emission lasts for only the pulse
      duration and can be intense. The radiation efficiency is shown to increase
      nonlinearly with laser intensity. Similar to cyclotron radiation, the radiation
      damping may restrain the maximal energy of relativistic electrons in ultraintense
      laser-produced plasmas.

PMID- 12005690
TI  - Experimental verification of the shear-modified ion-acoustic instability.
AB  - The predicted shear-induced shift of the wave phase velocity, the essence of the
      shear-modified ion-acoustic (SMIA) instability mechanism that reduces ion Landau
      damping for otherwise damped ion-acoustic waves [V. Gavrishchaka et al., 80, 728
      (1998)], is verified with direct measurements in a strongly magnetized laboratory
      plasma. The SMIA growth rate is shown to increase with increasing shear, as
      predicted. SMIA wave propagation is shown to be possible at both small and large
      angles to the magnetic field, consistent with space observations of ion-acoustic
      like waves.

PMID- 12005691
TI  - Precession of an electron-magnetohydrodynamic field-reversed configuration.
AB  - A field-reversed configuration is generated in a large laboratory plasma in the
      parameter regime of electron magnetohydrodynamics. During its free relaxation,
      the magnetic moment is observed to precess when tilted from its original axis.
      The precession velocity is the electron drift velocity in the toroidal current
      layer. The precession is a manifestation of frozen-in field lines in a moving
      electron fluid.

PMID- 12005692
TI  - Measurement of the current-density profile and plasma dynamics in the reversed
      field pinch.
AB  - First measurements of the current-density profile in the core of a high
      temperature reversed-field pinch are presented. The current-density profile is
      observed to peak during the sawtooth cycle and broaden promptly at the crash.
      This change in profile can be linked to magnetic relaxation and the dynamo which
      is predicted to drive antiparallel current in the plasma core. For high
      confinement discharges, the dynamo is suppressed and the current-density profile
      is observed to strongly peak.

PMID- 12005693
TI  - Dynamic topology of fullerene coalescence.
AB  - Atomic rearrangements leading to the coalescence of fullerene cages are revealed
      by topological analysis. Paths found for nanotubes and C(60) consist exclusively
      of Stone-Wales bond rotations. Computed intermediate states show gradual
      evolution from separate clusters to completely fused coherent units. Molecular
      dynamics simulations follow the predicted routes, overcome the nucleation
      barrier, and reach a final annealed state. While the overall behavior resembles
      macroscopic sintering, the nanoscale neck undergoes quantized changes in diameter
      and crystalline order.

PMID- 12005694
TI  - Microscopic formation mechanism of nanotube peapods.
AB  - Using molecular dynamics calculations, we investigate the absorption of a C(60)
      molecule in a (10,10) nanotube either through the open end or a large defect in
      the tube wall as possible scenarios for the hierarchical self-assembly of
      (C(60))(n)@(10,10) "nano-peapods." We find the absorption through a defect to be
      significantly more efficient than the end-on absorption. This process occurs most
      likely within a narrow launch velocity range for the fullerene that agrees well
      with the observed optimum temperature window for peapod formation.

PMID- 12005695
TI  - X-ray absorption holography.
AB  - The transmission of monochromatic x rays through a CoO single crystal was
      measured for different orientations of the sample. The small variations in the
      linear absorption coefficient were considered as a hologram and the real-space
      image of the local atomic environment was successfully reconstructed. The
      holographic signal constituted about 1% of the detected intensity. Besides other
      benefits, the use of the absorption holography can increase the signal-to
      background ratio by more than 1 order compared with the fluorescence holography.

PMID- 12005696
TI  - Watching ripples on crystals.
AB  - We present a new method for imaging surface phonon focusing and dispersion at
      frequencies up to 1 GHz that makes use of ultrafast optical excitation and
      detection. Animations of coherent surface phonon wave packets emanating from a
      point source on isotropic and anisotropic solids are obtained with micron lateral
      resolution. We resolve rounded-square shaped wave fronts on the (100) plane of
      LiF and discover isolated pockets of pseudosurface wave propagation with
      exceptionally high group velocity in the (001) plane of TeO(2). Surface phonon
      refraction and concentration in a minute gold pyramid is also revealed.

PMID- 12005697
TI  - Kinetics of capillary condensation in nanoscopic sliding friction.
AB  - The velocity and humidity dependence of nanoscopic sliding friction has been
      studied on CrN and diamondlike carbon surfaces with an atomic force microscope.
      The surface wettability is found to be decisive. Partially hydrophilic surfaces
      show a logarithmic decrease of friction with increasing velocity, the slope of
      which varies drastically with humidity, whereas on partially hydrophobic surfaces
      we confirm the formerly reported logarithmic increase. A model for the thermally
      activated nucleation of water bridges between tip and sample asperities fully
      reproduces the experimental data.

PMID- 12005698
TI  - Universality class of criticality in the restricted primitive model electrolyte.
AB  - The 1:1 equisized hard-sphere electrolyte or restricted primitive model has been
      simulated via grand-canonical fine-discretization Monte Carlo. Newly devised
      unbiased finite-size extrapolation methods using loci in the temperature-density
      or (T,rho) plane of isothermal rho(2-k) vs pressure inflections, of Q identical
      with<m(2)>(2)/<m(4)> maxima, and of canonical and C(V) criticality, yield
      estimates of (T(c),rho(c)) to +/-(0.04,3)%. Extrapolated exponents and Q ratio
      are (gamma,nu,Q(c)) = [1.24(3), 0.63(3); 0.624(2)], which support Ising (n = 1)
      behavior with (1.23(9), 0.630(3); 0.623(6)), but exclude classical, XY (n = 2),
      self-avoiding walk (n = 0), and n = 1 criticality with potentials
      varphi(r)>Phi/r(4.9) when r-->infinity.

PMID- 12005699
TI  - Mode-coupling theory for structural and conformational dynamics of polymer melts.
AB  - A mode-coupling theory for dense polymeric systems is developed which unifyingly
      incorporates the segmental cage effect relevant for structural slowing down and
      polymer chain conformational degrees of freedom. An ideal glass transition of
      polymer melts is predicted which becomes molecular-weight independent for large
      molecules. The theory provides a microscopic justification for the use of the
      Rouse theory in polymer melts, and the results for Rouse-mode correlators and
      mean-squared displacements are in good agreement with computer simulation
      results.

PMID- 12005700
TI  - Diffusion and thermal diffusion of semidilute to concentrated solutions of
      polystyrene in toluene in the vicinity of the glass transition.
AB  - The approaching glass transition in polystyrene/toluene solutions leads to a
      sharp decay of both the collective diffusion coefficient D and the thermal
      diffusion coefficient D(T) at concentrations above 0.2 g/cm(3). The Soret
      coefficient S(T) = D(T)/D follows power-law scaling from semidilute to
      concentrated and is not influenced by the slowing down of the dynamics associated
      with the glass transition. Both D and D(T) are governed by the same friction
      coefficient. The scaling behavior of S(T) with concentration on approach of the
      glass transition is compared to the divergence of S(T) near a consolute critical
      point.

PMID- 12005701
TI  - "Devil's staircases" in bulk-immiscible ultrathin alloy films.
AB  - Ground-state phase diagrams of ultrathin epitaxial alloy films are studied within
      the framework of a discrete lattice-model Hamiltonian incorporating competing
      elastic and chemical interactions. For bulk-immiscible alloy systems an infinite
      number of commensurate, long-period stripe-superstructure ground states are
      obtained as a function of chemical potential. The average periodicity of these
      stripe superstructures is found to be a nonmonotonic function of alloy
      composition, in contrast to the predictions of continuum theories for two
      dimensional systems with competing interactions.

PMID- 12005702
TI  - Elastic interaction of surface steps: effect of atomic-scale roughness.
AB  - Elastic interactions of atomic steps can greatly impact surface morphology.
      Recent atomistic calculations and experimental observations find the standard
      dipole model of steps is valid only for very large step separations. In this
      Letter, a new model is presented that displays remarkable agreement with
      atomistic predictions for step separations larger than just a few step heights.
      It is shown that the interaction energy of steps exhibits a novel intermediate
      ranged behavior and that, for particular systems, step interactions switch from
      repulsive to attractive as separation distance decreases.

PMID- 12005703
TI  - Ultranonlocality in time-dependent current-density-functional theory: application
      to conjugated polymers.
AB  - We solve the long-standing problem of the large overestimation of the static
      polarizability of conjugated polymers obtained using the local density
      approximation within density-functional theory. The local approximation is unable
      to describe the highly nonlocal exchange and correlation (xc) effects found in
      these quasi-one-dimensional systems. Time-dependent current-density-functional
      theory enables a local current description of ultranonlocal xc effects using the
      Vignale-Kohn functional [G. Vignale and W. Kohn, Phys. Rev. Lett. 77, 2037
      (1996)]. Except for the model hydrogen chain, our results are in excellent
      agreement with the best available correlated methods.

PMID- 12005704
TI  - Low frequency dynamics of disordered XY spin chains and pinned density waves:
      from localized spin waves to soliton tunneling.
AB  - A long-standing problem of the low-energy dynamics of a disordered XY spin chain
      is reexamined. The case of a rigid chain is studied, where the quantum effects
      can be treated quasiclassically. It is shown that, as the frequency decreases,
      the relevant excitations change from localized spin waves to two-level systems to
      soliton-antisoliton pairs. The linear-response correlation functions are
      calculated. The results apply to other periodic glassy systems such as pinned
      density waves, planar vortex lattices, stripes, and disordered Luttinger liquids.

PMID- 12005705
TI  - Inverse proximity effect in a strongly correlated electron system.
AB  - An anomalous superconducting proximity effect between a strongly correlated
      electron system and a normal metal is demonstrated. The model system is a 2D
      ultrathin superconducting quench-condensed Pb film. Such a highly disordered film
      has a reduced transition temperature (T(c) = 1.7 K) due to the strong e(-)-e(-)
      interaction. Instead of weakening the superconductivity, an overlayer of Ag on Pb
      induces an increase of both the T(c) and the gap. The restoration of the electron
      screening brought about by the quasiparticles from the normal metal can explain
      this striking inverse proximity effect.

PMID- 12005706
TI  - Nature of heavy quasiparticles in magnetically ordered heavy fermions UPd(2)Al(3)
      and UPt(3).
AB  - The optical conductivity of the heavy fermions UPd(2)Al(3) and UPt(3) has been
      measured in the energy range from 0.04 to 5 meV. In both compounds a well
      pronounced pseudogap of less than 1 meV develops in the optical response at low
      temperatures; we relate this to the antiferromagnetic ordering. From the energy
      dependence of the effective mass and scattering rate we conclude that the
      enhancement of the mass mainly occurs below the energy which is related to
      magnetic correlations between the local magnetic moments and the itinerant
      electrons. This implies that the magnetic order in these compounds is the
      prerequisite to the formation of the heavy quasiparticles and eventually to
      superconductivity.

PMID- 12005707
TI  - Realization of a large J(2) quasi-2D spin-half Heisenberg system: Li(2)VOSiO(4).
AB  - Exchange couplings are calculated for Li(2)VOSiO(4) using the local-density
      approximation (LDA). While the sum of in-plane couplings J(1)+J(2) = 9.5+/-1.5 K
      and the interplane coupling J( perpendicular) approximately 0.2- 0.3 K agree with
      recent experimental data, the ratio J(2)/J(1) approximately 12 exceeds the
      reported value by an order of magnitude. Using geometrical considerations, high
      temperature expansions and perturbative mean field theory, we show that the LDA
      derived exchange constants lead to a remarkably accurate description of the
      properties of these materials including specific heat, susceptibility, Neel
      temperature, and NMR spectra.

PMID- 12005708
TI  - Coherent electron transport in a Si quantum dot dimer.
AB  - We show that the coherence of charge transfer through a weakly coupled double-dot
      dimer can be determined by analyzing the statistics of the conductance pattern,
      and does not require a large phase coherence length in the host material. We
      present an experimental study of the charge transport through a small Si
      nanostructure, which contains two quantum dots. The transport through the dimer
      is shown to be coherent. At the same time, one of the dots is strongly coupled to
      the leads, and the overall transport is dominated by inelastic cotunneling
      processes.

PMID- 12005709
TI  - Electron spin decoherence in quantum dots due to interaction with nuclei.
AB  - We study the decoherence of a single electron spin in an isolated quantum dot
      induced by hyperfine interaction with nuclei. The decay is caused by the spatial
      variation of the electron wave function within the dot, leading to a nonuniform
      hyperfine coupling A. We evaluate the spin correlation function and find that the
      decay is not exponential but rather power (inverse logarithm) lawlike. For
      polarized nuclei we find an exact solution and show that the precession amplitude
      and the decay behavior can be tuned by the magnetic field. The decay time is
      given by (planck)N/A, where N is the number of nuclei inside the dot, and the
      amplitude of precession decays to a finite value. We show that there is a
      striking difference between the decoherence time for a single dot and the
      dephasing time for an ensemble of dots.

PMID- 12005710
TI  - Pauli paramagnetism and Landau level crossing in a modulation doped CdMnTe/CdMgTe
      quantum well.
AB  - Electrical transport measurements are reported on a 2DEG in a CdMnTe quantum well
      structure. The amplitude of the Shubnikov-de Haas oscillations show a distinct
      beating pattern with nodes corresponding to coincidences between the spin
      splitting and a half integer multiple of the cyclotron energy. The observed
      pattern of nodes is a direct consequence of the large Pauli paramagnetism induced
      by the s-d exchange interaction between the spins of electronic states and the
      localized magnetic moments.

PMID- 12005711
TI  - Robust D-wave pairing correlations in a hole-doped spin-fermion model.
AB  - Pairing correlations are studied numerically in a hole-doped spin-fermion model.
      Simulations performed on up to 12 x 12 clusters provide indications of D-wave
      superconductivity away from half-filling comparable to those of the 2D t-J model.
      The pairing correlations are the strongest in the direction perpendicular to the
      dynamic stripes that appear in the ground state at some densities. An optimal
      doping, where correlations are maximized, was observed at approximately 25%
      doping with an estimated T(c) approximately 100-200 K, in qualitative agreement
      with high-T(c) cuprates' phenomenology, while pairing correlations are suppressed
      by static stripe inhomogeneities.

PMID- 12005712
TI  - Response to tilted magnetic fields in Bi(2)Sr(2)CaCu(2)O(8) with columnar
      defects: evidence for transverse Meissner effect.
AB  - The transverse Meissner effect (TME) in the highly layered superconductor
      Bi(2)Sr(2)CaCu(2)O(8+y) with columnar defects is investigated by transport
      measurements. We present evidence for the persistence of the Bose glass phase for
      H(perpendicular)<H(perpendicular c): (i) the variable-range vortex hopping
      process crosses over to the half-loop regime; (ii) near H(perpendicular c) the
      energy barriers vanish linearly with H(perpendicular); (iii) the transition
      temperature is governed by T(BG)(H(parallel),0)
      T(BG)(H(parallel),H(perpendicular)) approximately /H(
      perpendicular)/(1/nu(perpendicular)) with nu(perpendicular) = 1.0 +/- 0.1.
      Furthermore, above the transition as H(perpendicular)-->H(+)(perpendicular c),
      moving kink chains consistent with a commensurate-incommensurate transition
      scenario are observed. These results show the existence of the TME for
      H(perpendicular)<H(perpendicular c).

PMID- 12005713
TI  - Optical and thermal-transport properties of an inhomogeneous d-wave
      superconductor.
AB  - We calculate transport properties of disordered 2D d-wave superconductors from
      solutions of the Bogoliubov-de Gennes equations, and show that weak localization
      effects give rise to a finite-frequency peak in the optical conductivity similar
      to that observed in experiments on disordered cuprates. At low energies, order
      parameter inhomogeneities induce linear and quadratic temperature dependencies in
      microwave and thermal conductivities respectively, and appear to drive the system
      towards a quasiparticle insulating phase.

PMID- 12005714
TI  - Competition of spin fluctuations and phonons in superconductivity of ZrZn(2).
AB  - It has long been suspected that spin fluctuations in ZrZn2 may lead to a triplet
      superconductivity. We point out another possibility, an inhomogeneous singlet
      (Fulde-Ferrell) state. We calculated the electronic structure, as well as the
      zone center phonons and their coupling with electrons. We find that the exchange
      splitting is nonuniform and the Fermi surface exhibits substantial nesting. Both
      factors favor a Fulde-Ferrell state at parts of the Fermi surface. We find a
      substantial coupling of Zr rattling modes with electrons, which can provide the
      necessary pairing in the s-channel.

PMID- 12005715
TI  - Low frequency magnetic response in antiferromagnetically coupled Fe/Cr
      multilayers.
AB  - The magnetic field and temperature dependence of the low frequency magnetic
      response of antiferromagnetically coupled Fe/Cr(100) multilayers has been studied
      between +/-500 Oe, from 2 to 300 K. At T = 2 K the losses exhibit an unusually
      strong frequency dependence which can be described within a single relaxation
      time scheme. This relaxation time proves to be strongly field dependent. These
      phenomena are specific for epitaxial multilayers with large magnetoresistance.
      The behavior of the relaxation time at low temperatures might be related to some
      quantum tunneling processes.

PMID- 12005716
TI  - Defect-induced magnetic structure in (Ga(1)-(x)Mn(x))As.
AB  - We show that magnetic structures involving partial disorder of local magnetic
      moments on the Mn atoms in (Ga(1)-(x)Mn(x))As lower the total energy, compared to
      the case of perfect ferromagnetic ordering, when As defects on the Ga sublattice
      are present. Such magnetic structures are found to be stable for a range of
      concentrations of As antisites, and this result accounts for the observed
      magnetic moments and critical temperatures in (Ga(1)-(x)Mn(x))As. We propose an
      explanation for the stabilization of the partially disordered magnetic structures
      and conclude that the magnetization and critical temperatures should increase
      substantially by reducing the number of As antisite defects.

PMID- 12005717
TI  - Segmented band mechanism for itinerant ferromagnetism.
AB  - We introduce a novel mechanism for itinerant ferromagnetism, which is based on a
      simple two-band model, and, by using numerical and analytical methods, we show
      that the periodic Anderson model contains this mechanism. We propose that the
      mechanism, which does not assume an intra-atomic Hund's coupling, is present in
      both the iron group and some f electron compounds.

PMID- 12005718
TI  - Wave refraction in negative-index media: always positive and very inhomogeneous.
AB  - We present the first treatment of the refraction of physical electromagnetic
      waves in newly developed negative index media (NIM), also known as left-handed
      media (LHM). The NIM dispersion relation implies that group fronts refract
      positively even when phase fronts refract negatively. This difference results in
      rapidly dispersing, very inhomogeneous waves. In fact, causality and finite
      signal speed always prevent negative wave signal (not phase) refraction. Earlier
      interpretations of phase refraction as "negative light refraction" and "light
      focusing by plane slabs" are therefore incorrect, and published NIM experiments
      can be explained without invoking negative signal refraction.

PMID- 12005719
TI  - Single-photon tunneling via localized surface plasmons.
AB  - Strong evidence of a single-photon tunneling effect, a direct analog of single
      electron tunneling, has been obtained in the measurements of light tunneling
      through individual subwavelength pinholes in a gold film covered with a layer of
      polydiacetylene. The transmission of some pinholes reached saturation because of
      the optical nonlinearity of polydiacetylene at a very low light intensity of a
      few thousand photons per second. This result is explained theoretically in terms
      of a "photon blockade," similar to the Coulomb blockade phenomenon observed in
      single-electron tunneling experiments. Single-photon tunneling may find
      applications in the fields of quantum communication and information processing.

PMID- 12005720
TI  - Systematic (63)Cu NQR and (89)Y NMR study of spin dynamics in Y(1
      z)Ca(z)Ba(2)Cu(3)O(y) across the superconductor-insulator boundary.
AB  - We demonstrate that the spin dynamics in underdoped Y(1-z)Ca(z)Ba(2)Cu(3)O(y) for
      y approximately equal to 6.0 exhibit qualitatively the same behavior to
      underdoped La(2-x)Sr(x)CuO(4) for an equal amount of hole concentration p = z/2 =
      x< or =0.11. However, a spin gap appears as more holes are doped into the CuO(2)
      plane by increasing the oxygen concentration to y approximately equal to 6.5 for
      a fixed value of Ca concentration z. Our results also suggest that Ca doping
      causes disorder effects that enhance the low frequency spin fluctuations.

PMID- 12005721
TI  - Narrow photoemission peak at the Fermi level in Fe/Cu(111).
AB  - We have studied electronic states of Fe adatoms deposited on Cu(111) by
      photoemission spectroscopy and have found a narrow peak at the Fermi level in the
      Fe 3d spectral function. The Fe 3d spectral function would be consistent with the
      Anderson impurity model, which has been widely used for the interpretation of
      bulk Ce and Yb compounds. This result indicates a strong reduction of
      hybridization between the Fe 3d state and the conduction-band states and an
      enhancement of effective Coulomb interaction for the Fe 3d electrons in an Fe
      adatom on Cu(111).

PMID- 12005722
TI  - Approximate quantum cloning with nuclear magnetic resonance.
AB  - Here we describe a nuclear magnetic resonance (NMR) experiment that uses a three
      qubit NMR device to implement the one-to-two approximate quantum cloning network
      of Buzek et al. [Phys. Rev. A 56, 3446 (1997)]. As expected the experimental
      results indicate that the network clones all input states with similar
      fidelities, but as a result of decoherence and incoherent evolution arising from
      B(1) inhomogeneity the total fidelity achieved does not exceed the measurement
      bound.

PMID- 12005723
TI  - Multiphoton entanglement concentration and quantum cryptography.
AB  - Multiphoton states from parametric down-conversion can be entangled both in
      polarization and photon number. Maximal high-dimensional entanglement can be
      concentrated postselectively from these states via photon counting. This makes
      them natural candidates for quantum key distribution, where the presence of more
      than one photon per detection interval has up to now been considered undesirable.
      We propose a simple multiphoton cryptography protocol for the case of low losses.

PMID- 12005724
TI  - Entanglement concentration using quantum statistics.
AB  - We propose an entanglement concentration scheme which uses only the effects of
      quantum statistics of indistinguishable particles. This establishes the fact that
      useful quantum information processing can be accomplished by quantum statistics
      alone. Because of the basis independence of statistical effects, our protocol
      requires less knowledge of the initial state than most entanglement concentration
      schemes. Moreover, no explicit controlled operation is required at any stage.

PMID- 12005725
TI  - Distinguishing separable and entangled states.
AB  - We show how to design families of operational criteria that distinguish entangled
      from separable quantum states. The simplest of these tests corresponds to the
      well-known Peres-Horodecki positive partial transpose (PPT) criterion, and the
      more complicated tests are strictly stronger. The new criteria are tractable due
      to powerful computational and theoretical methods for the class of convex
      optimization problems known as semidefinite programs. We successfully applied the
      results to many low-dimensional states from the literature where the PPT test
      fails. As a by-product of the criteria, we provide an explicit construction of
      the corresponding entanglement witnesses.

PMID- 12005726
TI  - Equilibrium shapes of flat knots.
AB  - We study the equilibrium shapes of prime and composite knots confined to two
      dimensions. Using scaling arguments we show that, due to self-avoiding effects,
      the topological details of prime knots are localized on a small portion of the
      larger ring polymer. Within this region, the original knot configuration can
      assume a hierarchy of contracted shapes, the dominating one given by just one
      small loop. This hierarchy is investigated in detail for the flat trefoil knot,
      and corroborated by Monte Carlo simulations.

PMID- 12005727
TI  - Pattern formation in flowing electrorheological fluids.
AB  - A two-fluid continuum model is developed to describe mass transport in electro-
      and magnetorheological suspensions. The particle flux is related to the field
      induced stresses. Solutions of the resulting mass balance show column formation
      in the absence of flow, and stripe formation when a suspension is subjected
      simultaneously to an applied electric field and shear flow.

PMID- 12005728
TI  - Hiding solutions in random satisfiability problems: a statistical mechanics
      approach.
AB  - A major problem in evaluating stochastic local search algorithms for NP-complete
      problems is the need for a systematic generation of hard test instances having
      previously known properties of the optimal solutions. On the basis of statistical
      mechanics results, we propose random generators of hard and satisfiable instances
      for the 3-satisfiability problem. The design of the hardest problem instances is
      based on the existence of a first order ferromagnetic phase transition and the
      glassy nature of excited states. The analytical predictions are corroborated by
      numerical results obtained from complete as well as stochastic local algorithms.

PMID- 12005729
TI  - Comment on "Orthorhombic Intermediate State in the Zinc Blende to Rocksalt
      Transformation Path of SiC at High Pressure".

PMID- 12005731
TI  - Comment on " Sn/Ge(111) Surface Charge-Density-Wave Phase Transition".

PMID- 12005733
TI  - Generalized nonadditive entropies and quantum entanglement.
AB  - We examine the inference of quantum density operators from incomplete information
      by means of the maximization of general nonadditive entropic forms. Extended
      thermodynamic relations are given. When applied to a bipartite spin 1 / 2 system,
      the formalism allows one to avoid fake entanglement for data based on the Bell
      Clauser-Horne-Shimony-Holt observable, and, in general, on any set of Bell
      constraints. Particular results obtained with the Tsallis entropy and with an
      introduced exponential entropic form are also discussed.

PMID- 12005734
TI  - Entangling many atomic ensembles through laser manipulation.
AB  - We propose an experimentally feasible scheme to generate the Greenberger-Horne
      Zeilinger-type of maximal entanglement between many atomic ensembles based on
      laser manipulation and single-photon detection. The scheme, with inherent fault
      tolerance to the dominant noise and efficient scaling of the efficiency with the
      number of ensembles, allows one to maximally entangle many atomic ensembles
      within the reach of current technology. Such a maximum entanglement of many
      ensembles has wide applications in the demonstration of quantum nonlocality, high
      precision spectroscopy, and quantum information processing.

PMID- 12005735
TI  - Stability of continuously pumped atom lasers.
AB  - A multimode model of a continuously pumped atom laser is shown to be unstable
      below a critical value of the scattering length. Above the critical scattering
      length, the atom laser reaches a steady state, the stability of which increases
      with pumping. Below this limit the laser does not reach a steady state. This
      instability results from the competition between gain and loss for the excited
      states of the lasing mode. It will determine a fundamental limit for the
      linewidth of an atom laser beam.

PMID- 12005736
TI  - Divergence-free WKB method.
AB  - A new semiclassical approach to the linear and nonlinear one-dimensional
      Schrodinger equation is presented. For both equations our zeroth-order solutions
      include nonperturbative quantum corrections to the WKB solution and the Thomas
      Fermi solution, thereby allowing us to make uniformly converging perturbative
      expansions of the wave functions. Our method leads to a new quantization
      condition that yields exact eigenenergies for the harmonic-oscillator and Morse
      potentials.

PMID- 12005737
TI  - Bell-type inequalities to detect true n-body nonseparability.
AB  - We analyze the structure of correlations among more than two quantum systems. We
      introduce a classification of correlations based on the concept of
      nonseparability, which is different a priori from the concept of entanglement.
      Generalizing a result of Svetlichny [Phys. Rev. D 35, 3066 (1987)] on three
      particle correlations, we find an inequality for n-particle correlations that
      holds under the most general separability condition and that is violated by some
      quantum-mechanical states.

PMID- 12005738
TI  - Quantum phases of dipolar bosons in optical lattices.
AB  - The ground state of dipolar bosons placed in an optical lattice is analyzed. We
      show that the modification of experimentally accessible parameters can lead to
      the realization and control of different quantum phases, including superfluid,
      supersolid, Mott insulator, checkerboard, and collapse phases.

PMID- 12005739
TI  - Exact c-number representation of non-Markovian quantum dissipation.
AB  - The reduced dynamics of a quantum system interacting with a linear heat bath
      finds an exact representation in terms of a stochastic Schrodinger equation. All
      memory effects of the reservoir are transformed into noise correlations and mean
      field friction. The classical limit of the resulting stochastic dynamics is shown
      to be a generalized Langevin equation, and conventional quantum state diffusion
      is recovered in the Born-Markov approximation. The non-Markovian exact dynamics,
      valid at arbitrary temperature and damping strength, is exemplified by an
      application to the dissipative two-state system.

PMID- 12005740
TI  - Quantum tunneling of Bose-Einstein condensates in optical lattices under gravity.
AB  - We investigate the quantum tunneling of Bose-Einstein condensates in optical
      lattices under gravity in the "Wannier-Stark localization" regime and "Landau
      Zener tunneling" regime. Our results agree with experimental data [B. P. Anderson
      et al., Science 282, 1686 (1998); F. S. Cataliotti et al., Science 293, 843
      (2001)]. We obtain the total decay rate which is valid over the entire range of
      temperatures, and show how it reduces to the appropriate results for the
      classical thermal activation at high temperatures, the thermally assisted
      tunneling at intermediate temperatures, and the pure quantum tunneling at low
      temperatures. We design an experimental protocol to observe this new phenomenon
      in further experiments.

PMID- 12005741
TI  - Proof of Bose-Einstein condensation for dilute trapped gases.
AB  - The ground state of bosonic atoms in a trap has been shown experimentally to
      display Bose-Einstein condensation (BEC). We prove this fact theoretically for
      bosons with two-body repulsive interaction potentials in the dilute limit,
      starting from the basic Schrodinger equation; the condensation is 100% into the
      state that minimizes the Gross-Pitaevskii energy functional. This is the first
      rigorous proof of BEC in a physically realistic, continuum model.

PMID- 12005742
TI  - Determination of absolute neutrino masses from bursts of Z bosons in cosmic rays.
AB  - Ultrahigh energy neutrinos (UHEnu) scatter on relic neutrinos (Rnu) producing Z
      bosons, which can decay hadronically producing protons (Z burst). We compare the
      predicted proton spectrum with the observed ultrahigh energy cosmic ray (UHECR)
      spectrum and determine the mass of the heaviest Rnu via a maximum likelihood
      analysis. Our prediction depends on the origin of the powerlike part of the UHECR
      spectrum: m(nu) = 2.75(+1.28)(-0.97) eV for Galactic halo and 0.26(+0.20)(-0.14)
      eV for extragalactic origin. The necessary UHEnu flux should be detected in the
      near future.

PMID- 12005743
TI  - n-n* oscillations in models with large extra dimensions.
AB  - We analyze n-n* oscillations in generic models with large extra dimensions in
      which standard-model fields propagate and fermion wave functions have strong
      localization. We find that in these models n-n* oscillations might occur at
      levels not too far below the current limit.

PMID- 12005746
TI  - The hypernuclei (4)(lambda)He and (4)(lambda)H: challenges for modern hyperon
      nucleon forces.
AB  - The hypernuclei (4)(Lambda)He and (4)(Lambda)H provide important information on
      the hyperon-nucleon interaction. We present accurate Faddeev-Yakubovsky
      calculations for the Lambda separation energies of the 0(+) ground and the 1(+)
      excited states based on the Nijmegen SC YN interactions. We explicitly take the
      Sigma admixture into account. Mass differences of the baryons and the charge
      dependence of the interaction are considered. The results show that the Nijmegen
      models cannot predict all separation energies simultaneously hinting to failures
      of the current interaction models. It is pointed out that the differences of the
      Lambda separation energies of (4)(Lambda)He and (4)(Lambda)H are interesting
      observables to probe the YN interaction models.

PMID- 12005747
TI  - 0(+)(gs) --> 2(+)(1) excitations in the mirror nuclei 32Ar and 32Si.
AB  - We measured the strength of the 0(+)(gs)-->2(+)(1) excitations in the radioactive
      mirror nuclei 32Ar and 32Si using the techniques of intermediate-energy Coulomb
      excitation for 32Ar and inelastic proton scattering in inverse kinematics for
      32Si. The 32Ar measurement, taken together with previously existing Coulomb
      excitation data for 32Si, yields the isoscalar and isovector multipole matrix
      elements for the 0(+)(1)-->2(+)(1) transition between T = 2 states in the A = 32
      system. The proton scattering measurement for 32Si, when combined with the
      Coulomb excitation data for this nucleus, yields a ratio of neutron and proton
      matrix elements, M(n)/M(p), for 32Si.

PMID- 12005748
TI  - Angular momentum and cross sections for fusion with weakly bound nuclei: breakup,
      a coherent effect.
AB  - Results for the cross section and average angular momentum for complete fusion at
      energies around the Coulomb barrier are presented for 7Li with 165Ho. Comparison
      of the cross sections with a one-dimensional barrier penetration model, using a
      potential consistent with the measured elastic scattering, showed a reduction
      above the barrier and an enhancement below it. An increase in the measured
      average angular momentum, <l>, above the barrier and its consistency with that
      obtained from the fusion excitation function for weakly bound nuclei, is
      reported. These results together with a reanalysis of existing data conclusively
      demonstrate that the effect of breakup on fusion is coherent, like coupling to
      any nonelastic channel.

PMID- 12005744
TI  - Precise measurement of B meson lifetimes with hadronic decay final states.
AB  - The lifetimes of the B(0) and B- mesons are extracted from 29.1 fb(-1) of data
      collected with the Belle detector at the KEK B factory. A fit to the decay length
      differences of neutral and charged B meson pairs, measured in events where one of
      the B mesons is fully reconstructed in several hadronic modes, yields tau(B(0)) =
      1.554+/-0.030(stat)+/-0.019(syst) ps, tau(B-) = 1.695+/-0.026(stat)+/-0.015(syst)
      ps, and tau(B-)/tau(B(0)) = 1.091+/-0.023(stat)+/-0.014(syst).

PMID- 12005749
TI  - Tunneling resonances and coherence in an optical lattice.
AB  - The center-of-mass quantization of atoms trapped in a gray optical lattice is
      observed to manifest itself in the steady-state properties of the atoms.
      Modulations in the lifetime and macroscopic magnetization as a function of an
      applied B field are attributed to quantum mechanical tunneling resonances and are
      shown to exist only under conditions which afford spatial coherence of the
      trapped atoms over several lattice wells and coherence times that exceed the
      tunneling period.

PMID- 12005750
TI  - Core-excited resonance enhancement in the two-photon complete fragmentation of
      helium.
AB  - A time-dependent close-coupling method is used to calculate, for the first time,
      fully differential cross sections for the complete fragmentation of helium by two
      photons. Surprising differences in the magnitude of the total-integral cross
      sections are found in comparisons with other calculations. These differences are
      found to be due to a core-excited resonance enhancement of the two-photon process
      for both single and double ionization. These calculations provide theoretical
      support for ground-breaking measurements expected to be obtained from free
      electron laser experiments in the near future.

PMID- 12005751
TI  - Measurement of transition dipole moments in lithium dimers using
      electromagnetically induced transparency.
AB  - We have observed electromagnetically induced transparency in a Doppler broadened
      molecular cascade system using fluorescence detection. We demonstrate that the
      power-dependent splitting of lines in the upper-level fluorescence excitation
      spectrum can be used as a new spectroscopic tool for the measurement of molecular
      transition dipole moment functions.

PMID- 12005752
TI  - Time-dependent close-coupling calculations of dielectronic capture in He.
AB  - We report on the first time-dependent close-coupling calculation of dielectronic
      capture into a doubly excited state of a two-electron atom. An incoming electron
      is represented by a Gaussian wave packet which collides with singly ionized
      helium in its ground state. The close-coupling equations describe the propagation
      of the total compound wave function on a two-dimensional radial lattice. By
      projecting this wave function onto a doubly excited state of neutral helium, we
      can determine the probability amplitude for dielectronic capture into one of
      these states and the subsequent autoionization from it.

PMID- 12005745
TI  - Search for the scalar top quark in pp collisions at square root[s] = 1.8 TeV.
AB  - We have performed a search for scalar top quark (stop) pair production in the
      inclusive electron-muon-missing transverse energy final state, using a sample of
      pp events corresponding to 108.3 pb(-1) of data collected with the D0 detector at
      Fermilab. The search is done in the framework of the minimal supersymmetric
      standard model assuming that the sneutrino is the lightest supersymmetric
      particle. For the dominant decays of the lightest stop, t-->b chi+1 and t-->blnu,
      no evidence for signal is found. We derive cross-section limits as a function of
      stop ( t ), chargino ( chi+1), and sneutrino ( nu) masses.

PMID- 12005753
TI  - Resonant control of elastic collisions in an optically trapped fermi gas of
      atoms.
AB  - We have loaded an ultracold gas of fermionic atoms into a far-off resonance
      optical dipole trap and precisely controlled the spin composition of the trapped
      gas. We have measured a magnetic-field Feshbach resonance between atoms in the
      two lowest energy spin states, /9/2,-9/2> and /9/2,-7/2>. The resonance peaks at
      a magnetic field of 201.5+/-1.4 G and has a width of 8.0+/-1.1 G. Using this
      resonance, we have changed the elastic collision cross section in the gas by
      nearly 3 orders of magnitude.

PMID- 12005754
TI  - Experimental evidence for supercontinuum generation by fission of higher-order
      solitons in photonic fibers.
AB  - We report on an experimental study of supercontinuum generation in photonic
      crystal fibers with low-intensity femtosecond pulses, which provides evidence for
      a novel spectral broadening mechanism. The observed results agree with our
      theoretical calculations carried out without making the slowly varying envelope
      approximation. Peculiarities of the measured spectra and their theoretical
      explanation demonstrate that the reason for the white-light generation in
      photonic crystal fibers is fission of higher-order solitons into redshifted
      fundamental solitons and blueshifted nonsolitonic radiation.

PMID- 12005755
TI  - Superfluidity versus disorder in the discrete nonlinear Schrodinger equation.
AB  - We study the discrete nonlinear Schrodinger equation (DNLS) in an annular
      geometry with on-site defects. The dynamics of a traveling plane-wave maps onto
      an effective nonrigid pendulum Hamiltonian. The different regimes include the
      complete reflection and refocusing of the initial wave, solitonic structures, and
      a superfluid state. In the superfluid regime, which occurs above a critical value
      of nonlinearity, a plane wave travels coherently through the randomly distributed
      defects. This superfluidity criterion for the DNLS is analogous to (yet very
      different from) the Landau superfluidity criteria in translationally invariant
      systems. Experimental implications for the physics of Bose-Einstein condensate
      gases trapped in optical potentials and of arrays of optical fibers are
      discussed.

PMID- 12005756
TI  - Attosecond streak camera.
AB  - An electron generated by x-ray photoionization can be deflected by a strong laser
      field. Its energy and angular distribution depends on the phase of the laser
      field at the time of ionization. This phase dependence can be used to measure the
      duration and chirp of single sub100-attosecond x-ray pulses.

PMID- 12005757
TI  - Quantum theory of attosecond XUV pulse measurement by laser dressed
      photoionization.
AB  - The first reported measurements of single attosecond pulses use laser dressed
      single-photon extreme ultraviolet (XUV) ionization of gas atoms. The
      determination of XUV pulse duration from the electron spectrum is based on a
      classical theory. Although classical models are known to give a qualitatively
      correct description of strong laser atom interaction, the validity must be
      scrutinized by a quantum-mechanical analysis. We establish a theoretical
      framework for the accurate temporal characterization of attosecond XUV pulses.
      Our analysis reveals an improved scheme that allows for direct experimental
      discrimination between single and multiple attosecond pulses.

PMID- 12005758
TI  - Synchronization of chaotic semiconductor laser systems: a vectorial coupling
      dependent scenario.
AB  - We demonstrate the influence of vectorial coupling on the synchronization
      behavior of complex systems. We study two semiconductor lasers subject to delayed
      optical feedback which are unidirectionally coherently coupled via their optical
      fields. Our experimental and numerical results demonstrate a characteristic
      synchronization scenario in dependence on the relative feedback phase leading
      cyclically from chaos synchronization to almost uncorrelated states, and back to
      chaos synchronization. Finally, we reveal the influence of the feedback phase on
      the dynamics of the solitary delay system.

PMID- 12005759
TI  - Permutation entropy: a natural complexity measure for time series.
AB  - We introduce complexity parameters for time series based on comparison of
      neighboring values. The definition directly applies to arbitrary real-world data.
      For some well-known chaotic dynamical systems it is shown that our complexity
      behaves similar to Lyapunov exponents, and is particularly useful in the presence
      of dynamical or observational noise. The advantages of our method are its
      simplicity, extremely fast calculation, robustness, and invariance with respect
      to nonlinear monotonous transformations.

PMID- 12005760
TI  - Collisional granular flow as a micropolar fluid.
AB  - We show that a micropolar fluid model successfully describes collisional granular
      flows on a slope. A micropolar fluid is the fluid with internal structures in
      which coupling between the spin of each particle and the macroscopic velocity
      field is taken into account. It is a hydrodynamical framework suitable for
      granular systems which consists of particles with macroscopic size. We
      demonstrate that the model equations can quantitatively reproduce the velocity
      and the angular velocity profiles obtained from the numerical simulation of the
      collisional granular flow on a slope using a simple estimate for the parameters
      in the theory.

PMID- 12005761
TI  - Sudden collapse of a granular cluster.
AB  - Single clusters in a vibro-fluidized granular gas in N connected compartments
      become unstable at strong shaking. They are experimentally shown to collapse very
      abruptly. The observed cluster lifetime (as a function of the driving intensity)
      is analytically calculated within a flux model, making use of the self-similarity
      of the process. After collapse, the cluster diffuses out into the uniform
      distribution in a self-similar way, with an anomalous diffusion exponent 1/3.

PMID- 12005762
TI  - Computational and experimental analysis of pinch-off and scaling.
AB  - Pinch-off and scaling during drop formation are studied using high-accuracy
      computation and ultrafast, high-resolution imaging. The interface of a water drop
      (viscosity mu is approximately 1 cP) is shown to overturn prior to breakup for
      the first time in experiments, well before the dynamics transitions from the
      potential flow (PF) to the inertial-viscous (IV) regime. A drop of 83% glycerol
      water solution (mu is approximately 85 cP) is shown to exhibit a transition from
      the PF to the IV regime both computationally and experimentally. The computed
      value of the minimum neck radius in the latter case follows Eggers's universal
      solution until it becomes unstable.

PMID- 12005763
TI  - Spontaneous branching of anode-directed streamers between planar electrodes.
AB  - Nonionized media subject to strong fields can become locally ionized by
      penetration of finger-shaped streamers. We study negative streamers between
      planar electrodes in a simple deterministic continuum approximation. We observe
      that, for sufficiently large fields, the streamer tip can split. This happens
      close to the limit of "ideal conductivity." Qualitatively, the tip splitting is
      due to a Laplacian instability quite like that in viscous fingering. For future
      quantitative analytical progress, our stability analysis of planar fronts
      identifies the screening length as a regularization mechanism.

PMID- 12005764
TI  - Model and observations of Schottky-noise suppression in a cold heavy-ion beam.
AB  - Some years ago it was found at GSI in Darmstadt that the momentum spread of
      electron-cooled beams of highly charged ions dropped abruptly to very low values
      when the particle number decreased to 10 000 or less. This has been interpreted
      as an ordering of the ions, such that they line up after one another in the ring.
      We report observations of similar transitions at CRYRING, including an
      accompanying drop in Schottky-noise power. We also introduce a model of the
      ordered beam from which the Schottky-noise power can be calculated numerically.
      The good agreement between the model calculation and the experimental data is
      seen as evidence for a spatial ordering of the ions.

PMID- 12005765
TI  - Experimental observations of transverse shear waves in strongly coupled dusty
      plasmas.
AB  - We report experimental observations of transverse shear waves in a three
      dimensional dusty plasma that is in the strongly coupled fluid regime. These
      spontaneous oscillations occur when the ambient neutral pressure is reduced below
      a threshold value and the measured dispersion characteristics of these waves are
      found to be in good agreement with predictions of a viscoelastic theory of dusty
      plasmas.

PMID- 12005766
TI  - Avalanche behavior in yield stress fluids.
AB  - We show that, above a critical stress, typical yield stress fluids (gels and clay
      suspensions) and soft glassy materials (colloidal glasses) start flowing abruptly
      and subsequently accelerate, leading to avalanches that are remarkably similar to
      those of granular materials. Rheometrical tests reveal that this is associated
      with a bifurcation in rheological behavior: for small stresses, the viscosity
      increases in time; the material eventually stops flowing. For slightly larger
      stresses the viscosity decreases continuously in time; the flow accelerates. Thus
      the viscosity jumps discontinuously to infinity at the critical stress. We
      propose a simple physical model capable of reproducing these effects.

PMID- 12005767
TI  - Quantum antidot formation and correlation to optical shift of gold nanoparticles
      embedded in MgO.
AB  - Quantum antidots are subnanometer scale vacancy clusters, the localized
      electronic structure of which can significantly alter the properties of a
      nanomaterial. We use positron spectroscopy to study vacancy clusters generated
      during the formation of gold nanoparticles via ion implantation in an MgO matrix.
      We observed that quantum antidots are associated with the nanoparticle surfaces
      after annealing in an O2 atmosphere, but not after annealing in a H2 atmosphere.
      In the former case, the presence of quantum antidots bound to the gold
      nanoparticles correlates with the redshift of the gold surface plasmon resonance,
      thus allowing an explanation for the redshift based on the transfer of electrons
      away from the metal particles.

PMID- 12005768
TI  - Origin of the stability of Ge(105) on si: a new structure model and surface
      strain relaxation.
AB  - The structure of Ge(105)-(1 x 2) grown on Si(105) is examined by scanning
      tunneling microscopy (STM) and first-principles calculations. The morphology
      evolution with an increasing amount of Ge deposited documents the existence of a
      tensile surface strain in Si(105) and its relaxation with increasing coverage of
      Ge. A detailed analysis of high-resolution STM images and first-principles
      calculations produce a new stable model for the Ge(105)-(1 x 2) structure formed
      on the Si(105) surface that includes the existence of surface strain. It corrects
      the model developed from early observations of the facets of "hut" clusters grown
      on Si(001).

PMID- 12005769
TI  - Anharmonic Raman spectra in high-pressure ice from ab initio simulations.
AB  - We calculate from ab initio molecular dynamics the Raman scattering of high
      pressure ice. To this effect we apply a new method based on the Berry phase
      theory of polarization. Our results are in agreement with recent and difficult
      experiments and are compatible with a picture in which ice VII is a proton
      disordered system and in ice X the hydrogen bond is symmetric.

PMID- 12005770
TI  - Electrically controlled nuclear spin polarization and relaxation by quantum-Hall
      states.
AB  - We study interactions between electrons and nuclear spins by using the resistance
      ( Rxx) peak which develops near the Landau-level filling factor nu = 2/3 as a
      probe. Temporarily tuning nu to a different value, nu(temp), with a gate
      demonstrates that the Rxx peak regenerates even after complete depletion (
      nu(temp) = 0), while it rapidly relaxes on either side of nu(temp) = 1. This
      indicates that the nu = 2/3 domain morphology is memorized by the nuclear spins
      which can be rapidly depolarized by Skyrmions. An additional enhancement in the
      nuclear spin relaxation around nu = 1/2 and 3/2 suggests a Fermi sea of partially
      polarized composite fermions.

PMID- 12005771
TI  - Variable range hopping in two-dimensional systems of interacting electrons.
AB  - Computer modeling of the variable-range-hopping (VRH) conductivity in two
      dimensional systems has been done by a kinetic Monte Carlo method, which includes
      some new elements. Study of the temperature dependence of the conductivity,
      testing of the different scaling relations, and study of the size effect show the
      detailed validity of the Efros-Shklovskii theory of the VRH in the system of
      interacting electrons. It has also been shown that simultaneous transitions of
      many electrons are not important. The reasons for disagreement with previous
      computational works are thoroughly analyzed.

PMID- 12005772
TI  - Localization of optically excited states by self-trapping.
AB  - We discuss the localization of the surface exciton at the Si(111)- (2x1) surface
      due to self-trapping, which leads to a characteristic temperature-dependent
      linewidth of the optical response and to a significant Stokes shift of the
      luminescence. Self-trapping results in this case from a structural relaxation in
      the excited state, caused by the interplay between electronic and geometric
      degrees of freedom. The most significant contribution to this effect comes from
      one single geometric deformation mode which is driven by the internal electronic
      charge transfer in the self-trapped exciton.

PMID- 12005773
TI  - Transition from an electron solid to the sequence of fractional quantum Hall
      states at very low Landau level filling factor.
AB  - At low Landau level filling of a two-dimensional electron system, typically
      associated with the formation of an electron crystal, we observe local minima in
      Rxx at filling factors nu = 2/11, 3/17, 3/19, 2/13, 1/7, 2/15, 2/17, and 1/9.
      Each of these developing fractional quantum Hall (FQHE) states appears only above
      a filling-factor-specific temperature. This can be interpreted as the melting of
      an electron crystal and subsequent FQHE liquid formation. The observed sequence
      of FQHE states follows the series of composite fermion states emanating from nu =
      1/6 and nu = 1/8.

PMID- 12005774
TI  - Nonequilibrium quasiparticle distribution induced by Kondo defects.
AB  - It is shown that in resistive nanowires out of equilibrium containing either
      single- or two-channel Kondo impurities the distribution function f(E,U) obeys
      scaling behavior in terms of the quasiparticle energy E and the bias voltage U.
      The numerically calculated f(E,U) curves explain quantitatively recent
      experiments on Cu and Au nanowires. The systematics of the impurity concentration
      c(imp) extracted from the comparison between theory and results on various Cu and
      Au samples strongly suggests that in these systems the scaling arises from
      magnetic Kondo impurities.

PMID- 12005775
TI  - Driving current through single organic molecules.
AB  - We investigate electronic transport through two types of conjugated molecules.
      Mechanically controlled break junctions are used to couple thiol end groups of
      single molecules to two gold electrodes. Current-voltage characteristics ( IVs)
      of the metal-molecule-metal system are observed. These IVs reproduce the spatial
      symmetry of the molecules with respect to the direction of current flow. We
      hereby unambiguously detect an intrinsic property of the molecule and are able to
      distinguish the influence of both the molecule and the contact to the metal
      electrodes on the transport properties of the compound system.

PMID- 12005776
TI  - Charge distribution in a Kondo-correlated quantum dot.
AB  - We report on direct measurement of charge and its distribution in a Kondo
      correlated quantum dot (QD). A noninvasive potential-sensitive detector, in
      proximity with a QD, reveals that, although the conductance of the QD is
      significantly enhanced as it enters the Kondo regime, the average charge remains
      unaffected. This demonstrates the separation between spin and charge degrees of
      freedom. We find, however, under certain conditions, an abrupt redistribution of
      charge in the QD, taking place with an onset of Kondo correlation. This suggests
      a correlation between the spin and charge degrees of freedom.

PMID- 12005777
TI  - Field-induced spin-sensity-wave phases in quasi-one-dimensional conductors:
      theory versus experiments.
AB  - We show that the "quantized nesting" model misses important features of the
      magnetic-field-induced spin-density-wave (FISDW) phase diagram. Among them are
      the following: (1) the FISDW wave vector is not strictly quantized; (2) in some
      compounds, the FISDW diagram consists of two regions: (a) At low temperatures,
      there are jumps of the wave vector (i.e., the first order transitions between
      FISDW phases); (b) at high temperatures the jumps and the first order transitions
      disappear, but the wave vector is still a nontrivial function of a magnetic
      field. These are in agreement with the experiments on (TMTSF)2PF6.

PMID- 12005778
TI  - Dual neutral variables and knot solitons in triplet superconductors.
AB  - We derive a dual presentation of a free energy functional for spin-triplet
      superconductors in terms of gauge-invariant variables. The resulting equivalent
      model in ferromagnetic phase has a form of a version of the Faddeev model. This
      allows one, in particular, to conclude that spin-triplet superconductors allow
      formation of stable finite-length closed vortices (knotted solitons).

PMID- 12005779
TI  - d-wave induced zero-field resonances in dc pi-superconducting quantum
      interference devices.
AB  - A dc pi SQUID consists of a superconducting ring interrupted by two Josephson
      junctions, one of which carries in equilibrium a pi phase difference, caused, for
      example, by the d-wave pairing symmetry of the high- T(c) cuprates. If this phase
      shift is maintained in the voltage state, anomalous resonance currents are
      expected in the SQUIDs transport characteristics. Here we report the observation
      of such resonances for high- T(c) dc pi SQUIDs, providing evidence for the
      influence of the d-wave symmetry on the voltage state of a Josephson junction for
      frequencies of several tens of GHz.

PMID- 12005780
TI  - Anomalous magnetic field dependence of the thermodynamic transition line in the
      isotropic superconductor (K,Ba)BiO3.
AB  - Thermodynamic (specific heat, reversible magnetization, tunneling spectroscopy)
      and transport measurements have been performed on high quality (K,Ba)BiO3 single
      crystals. The temperature dependence of the magnetic field H(C(p)) corresponding
      to the onset of the specific heat anomaly presents a clear positive curvature.
      H(C(p)) is significantly smaller than the field H(Delta) for which the
      superconducting gap vanishes but is closely related to the irreversibility line
      deduced from transport data. Moreover, the temperature dependence of the
      reversible magnetization presents a strong deviation from the Ginzburg-Landau
      theory emphasizing the peculiar nature of the superconducting transition in this
      material.

PMID- 12005781
TI  - Critical exponents of the random-field O(N) model.
AB  - The critical behavior of the random-field Ising model has long been a puzzle.
      Different methods predict that its critical exponents in D dimensions are the
      same as in the pure (D-2)-dimensional ferromagnet with the same number of the
      magnetization components contrary to the experiments and simulations. We
      calculate the exponents of the random-field O(N) model with the (4+epsilon)
      expansion and obtain values different from the exponents of the pure ferromagnet
      in 2+epsilon dimensions. An infinite set of relevant operators missed in previous
      studies leads to a breakdown of the (6-epsilon)-expansion.

PMID- 12005782
TI  - Evidence for two distinct energy scales in the Raman spectra of YBa2(Cu1
      xNix)3O6.95.
AB  - We report electronic Raman scattering from Ni-substituted YBa2Cu3O6.95 single
      crystals with T(c) ranging from 92.5 to 78 K. The fully symmetrical A(1g) channel
      and the B(1g) channel which is sensitive to the d(x(2)-y(2)) gap maximum have
      been explored. The energy of the B(1g) pair-breaking peak remains constant under
      Ni doping while the energy of the A(1g) peak scales with T(c) ( E(A(1g))/k(B)T(c)
      = 5). Our data show that the A(1g) peak tracks the magnetic resonance peak
      observed in inelastic neutron scattering yielding a key explanation to the long
      standing problem of the origin of the A(1g) peak.

PMID- 12005783
TI  - Long polaron lifetime in InAs/GaAs self-assembled quantum dots.
AB  - We have investigated the polaron dynamics in n-doped InAs/GaAs self-assembled
      quantum dots by pump-probe midinfrared spectroscopy. A long T1 polaron decay time
      is measured at both low temperature and room temperature, with values around 70
      and 37 ps, respectively. The decay time decreases for energies closer to the
      optical phonon energy. The relaxation is explained by the strong coupling for the
      electron-phonon interaction and by the finite lifetime of the optical phonons. We
      show that, even for a large detuning of 19 meV from the LO photon energy in GaAs,
      the carrier relaxation remains phonon assisted.

PMID- 12005784
TI  - Momentum-resolved charge excitations in a prototype one-dimensional mott
      insulator.
AB  - We report momentum-resolved charge excitations in a one-dimensional (1D) Mott
      insulator studied using high resolution inelastic x-ray scattering over the
      entire Brillouin zone for the first time. Excitations at the insulating gap edge
      are found to be highly dispersive (momentum dependent) compared to excitations
      observed in two-dimensional Mott insulators. The observed dispersion in 1D
      cuprates ( SrCuO2 and Sr2CuO3) is consistent with charge excitations involving
      holons which is unique to spin-1/2 quantum chain systems. These results point to
      the potential utility of momentum-resolved inelastic x-ray scattering in
      providing valuable information about electronic structure of strongly correlated
      insulators.

PMID- 12005785
TI  - Laser phase modulation approaches towards ensemble quantum computing.
AB  - Selective control of decoherence is demonstrated for a multilevel system by
      generalizing the instantaneous phase of any chirped pulse as individual terms of
      a Taylor series expansion. In the case of a simple two-level system, all odd
      terms in the series lead to population inversion, while the even terms lead to
      self-induced transparency. These results also hold for multiphoton transitions
      that do not have any lower-order photon resonance or any intermediate virtual
      state dynamics within the laser pulse width. Such results form the basis of a
      robustly implementable CNOT gate.

PMID- 12005786
TI  - Tracer diffusion in a dislocated lamellar system.
AB  - Many lamellar systems exhibit strongly anisotropic diffusion. When the diffusion
      across the lamellae is slow, an alternative mechanism for transverse transport
      becomes important. A tracer particle can propagate across the lamellae by
      encircling a screw dislocation. We calculate the statistical properties of this
      mode of transverse transport. When either positive or negative dislocations are
      in excess, transport across the lamellae is ballistic. When the average
      dislocation charge is zero, the mean square of the normal displacement grows like
      TlogT for large times. To obtain this result, the trajectory of the tracer must
      be smoothed over distances of order of the dislocation core size.

PMID- 12005787
TI  - Unified scaling law for earthquakes.
AB  - We show that the distribution of waiting times between earthquakes occurring in
      California obeys a simple unified scaling law valid from tens of seconds to tens
      of years. The short time clustering, commonly referred to as aftershocks, is
      nothing but the short time limit of the general hierarchical properties of
      earthquakes. There is no unique operational way of distinguishing between main
      shocks and aftershocks. In the unified law, the Gutenberg-Richter b value, the
      exponent -1 of the Omori law for aftershocks, and the fractal dimension d(f) of
      earthquakes appear as critical indices.

PMID- 12005788
TI  - Optimizing searches via rare events.
AB  - Randomized search algorithms for hard combinatorial problems exhibit a large
      variability of performances. We study the different types of rare events which
      occur in such out-of-equilibrium stochastic processes and we show how they
      cooperate in determining the final distribution of running times. As a by-product
      of our analysis we show how search algorithms are optimized by random restarts.

PMID- 12005789
TI  - Comment on "Feynman effective classical potential in the Schrodinger
      formulation".

PMID- 12005791
TI  - Comment on "Intrinsic ferroelectric coercive field".

PMID- 12005793
TI  - Spatiotemporal coherence resonance of phase synchronization in weakly coupled
      chaotic oscillators.
AB  - We study phase synchronization (PS) of coupled chaotic oscillators as a result of
      an interplay between local coupling and global noise. In the weak coupling
      region, noise first significantly enhances spatiotemporal PS, but it spoils the
      phase coherence of chaotic oscillation and reduces the degree of synchronization
      at large intensities. The spatiotemporal behavior exhibits coherence resonance.
      Noise enhanced phase synchronization is of great relevance to ecology.

PMID- 12005794
TI  - Driven inelastic Maxwell models with high energy tails.
AB  - The solutions of the homogeneous nonlinear Boltzmann equation for inelastic
      Maxwell models, when driven by different types of thermostats, show, in general,
      overpopulated high energy tails of the form approximately exp(-ac), with power
      law tails and Gaussian tails as border line cases. The results are compared with
      those for inelastic hard spheres, and a comprehensive picture of the long time
      behavior in freely cooling and driven inelastic systems is presented.

PMID- 12005795
TI  - Rotational dynamics of hydration water in dicalcium silicate by quasielastic
      neutron scattering.
AB  - Quasielastic neutron scattering (QENS) has been used to investigate the single
      particle dynamics of interfacial water in dicalcium silicate (C2S)/water paste.
      Our previous neutron-scattering studies on interfacial water have focused
      attention on the translational dynamics of the center of mass of water molecules.
      In this paper, we have collected QENS data on a wider range of wave-vector
      transfer so that both translational and rotational motions of water molecules are
      detected. The data have been analyzed by models for translation and rotation we
      recently proposed for supercooled water. The evolution of the parameters
      describing the relaxational dynamics of water embedded in the C2S matrix is given
      at temperature T=303 K as a function of the curing time.

PMID- 12005796
TI  - Observation of the soft-mode condensation in the Sm-A-Sm-C(*)(alpha) phase
      transition by nonlinear dielectric spectroscopy.
AB  - We have theoretically and experimentally studied the nonlinear dielectric
      response under large orientational fluctuations near the Sm-A-Sm-C(*)(alpha)
      phase transition point in a chiral smectic liquid crystal. The third-order
      nonlinear dielectric response due to the fluctuations was observed in the
      vicinity of the transition point. By using it, we have successfully observed the
      soft-mode condensation inducing the Sm-A-Sm-C(*)(alpha) phase transition.

PMID- 12005797
TI  - Statistics of selectively neutral genetic variation.
AB  - Random models of evolution are instrumental in extracting rates of microscopic
      evolutionary mechanisms from empirical observations on genetic variation in
      genome sequences. In this context it is necessary to know the statistical
      properties of empirical observables (such as the local homozygosity, for
      instance). Previous work relies on numerical results or assumes Gaussian
      approximations for the corresponding distributions. In this paper we give an
      analytical derivation of the statistical properties of the local homozygosity and
      other empirical observables assuming selective neutrality. We find that such
      distributions can be very non-Gaussian.

PMID- 12005798
TI  - DNA hybridization to mismatched templates: a chip study.
AB  - High-density oligonucleotide arrays are among the most rapidly expanding
      technologies in biology today. In the GeneChip system, the reconstruction of the
      sample mRNA concentrations depends upon the differential signal generated by
      hybridizing the RNA to two nearly identical templates: a perfect match probe (PM)
      containing the exact biological sequence; and a single mismatch (MM) differing
      from the PM by a single base substitution. It has been observed that a large
      fraction of MMs repetitively bind targets better than the PMs, against the
      obvious expectation of sequence specificity. We examine this problem via
      statistical analysis of a large set of microarray experiments. We classify the
      probes according to their signal to noise (S/N) ratio, defined as the
      eccentricity of a (PM,MM) pair's "trajectory" across many experiments. Of those
      probes having large S/N (>3) only a fraction behave consistently with the
      commonly assumed hybridization model. Our results imply that the physics of DNA
      hybridization in microarrays is more complex than expected, and suggest
      estimators for the target RNA concentration.

PMID- 12005799
TI  - Role of body rotation in bacterial flagellar bundling.
AB  - In bacterial chemotaxis, E. coli cells drift up chemical gradients by a series of
      runs and tumbles. Runs are periods of directed swimming, and tumbles are abrupt
      changes in swimming direction. Near the beginning of each run, the rotating
      helical flagellar filaments that propel the cell form a bundle. Using resistive
      force theory, we show that the counterrotation of the cell body necessary for
      torque balance is sufficient to wrap the filaments into a bundle, even in the
      absence of the swirling flows produced by each individual filament.

PMID- 12005800
TI  - Random walk with memory enhancement and decay.
AB  - A model of random walk with memory enhancement and decay was presented on the
      basis of the characteristics of the biological intelligent walks. In this model,
      the movement of the walker is determined by the difference between the remaining
      information at the jumping-out site and jumping-in site. The amount of the memory
      information s(i)(t) at a site i is enhanced with the increment of visiting times
      to that site, and decays with time t by the rate e(-beta(t)), where beta is the
      memory decay exponent. When beta=0, there exists a transition from Brownian
      motion (BM) to the compact growth of walking trajectory with the density of
      information energy u increasing. But for beta>0, this transition does not appear
      and the walk with memory enhancement and decay can be considered as the BM of the
      mass center of the cluster composed of remembered sites in the late stage.

PMID- 12005801
TI  - Persistence of a continuous stochastic process with discrete-time sampling: non
      Markov processes.
AB  - We consider the problem of "discrete-time persistence," which deals with the zero
      crossings of a continuous stochastic process X(T) measured at discrete times
      T=nDeltaT. For a Gaussian stationary process the persistence (no crossing)
      probability decays as exp(-theta(D)T)=[rho(a)](n) for large n, where a=exp(
      DeltaT/2) and the discrete persistence exponent theta(D) is given by theta(D)=(ln
      rho)/(2 ln a). Using the "independent interval approximation," we show how
      theta(D) varies with DeltaT for small DeltaT and conclude that experimental
      measurements of persistence for smooth processes, such as diffusion, are less
      sensitive to the effects of discrete sampling than measurements of a randomly
      accelerated particle or random walker. We extend the matrix method developed by
      us previously [Phys. Rev. E 64, 015101(R) (2001)] to determine rho(a) for a two
      dimensional random walk and the one-dimensional random-acceleration problem. We
      also consider "alternating persistence," which corresponds to a<0, and calculate
      rho(a) for this case.

PMID- 12005802
TI  - Stochastic solution of space-time fractional diffusion equations.
AB  - Classical and anomalous diffusion equations employ integer derivatives,
      fractional derivatives, and other pseudodifferential operators in space. In this
      paper we show that replacing the integer time derivative by a fractional
      derivative subordinates the original stochastic solution to an inverse stable
      subordinator process whose probability distributions are Mittag-Leffler type.
      This leads to explicit solutions for space-time fractional diffusion equations
      with multiscaling space-fractional derivatives, and additional insight into the
      meaning of these equations.

PMID- 12005803
TI  - Diffusion of a nearly spherical deformable body in a randomly stirred host fluid.
AB  - The motion of a deformable body is investigated for cases in which the body is
      immersed in an incompressible fluid that is randomly stirred. Sticking to
      physical situations in which the body departs only slightly from its spherical
      shape, we show that the motion of its center is decoupled from its deformation
      degrees of freedom. We study the general case in which the velocity field,
      imposed on the system, is correlated both in space and time. We derive the mean
      squared displacement of the body for the general random velocity field, and
      consider several useful cases including: white-noise flow, turbulence-like flow,
      and thermal agitation.

PMID- 12005804
TI  - Coherence resonance versus synchronization in a periodically forced self
      sustained system.
AB  - A fundamental relationship between coherence resonance (CR) and phase
      synchronization in a self-sustained system in the presence of noise is addressed.
      A Van der Pol system synchronized by external forcing is taken as an example. It
      is shown that, in breaking down synchronization, applied noise creates a new
      ordered motion whose coherence depends resonantly on its intensity, i.e., CR
      occurs. The same is true for both types of synchronization, via phase locking and
      via suppression: only the mechanisms of CR differ. The result is valid for any
      order n:m of synchronization.

PMID- 12005805
TI  - Potential energy landscape and mechanisms of diffusion in liquids.
AB  - The mechanism of diffusion in supercooled liquids is investigated from the
      potential energy landscape point of view, with emphasis on the crossover from
      high- to low-T dynamics over the range T(A) > or =T > or =T(c). Molecular
      dynamics simulations with a time dependent mapping to the associated local
      minimum or inherent structure (IS) are performed on unit-density Lennard-Jones.
      Dynamical quantities introduced include r2(is)(t), the mean-square displacement
      (MSD) within a basin of attraction of an IS, R2(t), the MSD of the IS itself, and
      g(t), the distribution of IS waiting times. The configuration space is treated as
      a composite of the contributions of cooperative local regions, and a method is
      given to obtain the physically meaningful g(loc)(t) and mean waiting time
      tau(loc) from g(t). An understanding of the crossover is obtained in terms of
      r2(is)(t) and tau(loc). At intermediate T, r2(is)(t) possesses an interval of
      linear t dependence allowing calculation of an intrabasin diffusion constant
      D(is). Near T(c), where intrabasin diffusion is well established for t<tau(loc),
      diffusion is intrabasin dominated with D=D(is); D may be calculated within a
      basin. Below T(c), tau(loc) exceeds the time tau(pl) needed for the system to
      explore the basin, indicating the action of barriers at the border;
      tau(loc)=tau(pl) is a criterion for transition to activated hopping. Intrabasin
      diffusion provides a means of confinement not involving barriers and plays a key
      role in the dynamics above T(c). The distinction is discussed between motion
      among the IS (IS dynamics) below T(c) and saddle or border dynamics above T(c),
      where the system is always close to one of the saddle barriers connecting the
      basins and IS boundaries are closely spaced and easily crossed. A border index is
      introduced based upon the relation of R2(t) to the conventional MSD, and shown to
      vanish at T approximately T(c). It is proposed that intrabasin diffusion is a
      manifestation of saddle dynamics.

PMID- 12005806
TI  - Effect of nonstationarities on detrended fluctuation analysis.
AB  - Detrended fluctuation analysis (DFA) is a scaling analysis method used to
      quantify long-range power-law correlations in signals. Many physical and
      biological signals are "noisy," heterogeneous, and exhibit different types of
      nonstationarities, which can affect the correlation properties of these signals.
      We systematically study the effects of three types of nonstationarities often
      encountered in real data. Specifically, we consider nonstationary sequences
      formed in three ways: (i) stitching together segments of data obtained from
      discontinuous experimental recordings, or removing some noisy and unreliable
      parts from continuous recordings and stitching together the remaining parts-a
      "cutting" procedure commonly used in preparing data prior to signal analysis;
      (ii) adding to a signal with known correlations a tunable concentration of random
      outliers or spikes with different amplitudes; and (iii) generating a signal
      comprised of segments with different properties-e.g., different standard
      deviations or different correlation exponents. We compare the difference between
      the scaling results obtained for stationary correlated signals and correlated
      signals with these three types of nonstationarities. We find that introducing
      nonstationarities to stationary correlated signals leads to the appearance of
      crossovers in the scaling behavior and we study how the characteristics of these
      crossovers depend on (a) the fraction and size of the parts cut out from the
      signal, (b) the concentration of spikes and their amplitudes (c) the proportion
      between segments with different standard deviations or different correlations and
      (d) the correlation properties of the stationary signal. We show how to develop
      strategies for preprocessing "raw" data prior to analysis, which will minimize
      the effects of nonstationarities on the scaling properties of the data, and how
      to interpret the results of DFA for complex signals with different local
      characteristics.

PMID- 12005807
TI  - Nonlinear anomalous diffusion equation and fractal dimension: exact generalized
      Gaussian solution.
AB  - In this work we incorporate, in a unified way, two anomalous behaviors, the power
      law and stretched exponential ones, by considering the radial dependence of the N
      dimensional nonlinear diffusion equation partial differential rho/ partial
      differential t=nabla.(Knablarho(nu))-nabla.(muFrho)-alpharho, where K=Dr(-theta),
      nu, theta, mu, and D are real parameters, F is the external force, and alpha is a
      time-dependent source. This equation unifies the O'Shaughnessy-Procaccia
      anomalous diffusion equation on fractals (nu=1) and the spherical anomalous
      diffusion for porous media (theta=0). An exact spherical symmetric solution of
      this nonlinear Fokker-Planck equation is obtained, leading to a large class of
      anomalous behaviors. Stationary solutions for this Fokker-Planck-like equation
      are also discussed by introducing an effective potential.

PMID- 12005808
TI  - Dispersal probability distributions and the wave-front speed problem.
AB  - The speed and width of front solutions to reaction-dispersal models are analyzed
      both analytically and numerically. We perform our analysis for Laplace and
      Gaussian distribution kernels, both for delayed and nondelayed models. The
      results are discussed in terms of the characteristic parameters of the models.

PMID- 12005809
TI  - Deterministic ratchets: route to diffusive transport.
AB  - The rectification efficiency of an underdamped ratchet operated in the adiabatic
      regime increases according to a scaling current-amplitude curve as the damping
      constant approaches a critical threshold; below threshold the rectified signal
      becomes extremely irregular and eventually its time average drops to zero.
      Periodic (locked) and diffusive (fully chaotic) trajectories coexist on fine
      tuning the amplitude of the input signal. The transition from regular to chaotic
      transport in noiseless ratchets has been studied numerically.

PMID- 12005810
TI  - Effects of ionization in single-bubble sonoluminescence.
AB  - We studied the effects of ionization in a sonoluminescing (SL) bubble within the
      hydrodynamic framework. The thermodynamic variables and the degrees of ionization
      inside the bubble throughout an oscillation cycle are obtained by solving the
      hydrodynamic equations assuming spherical symmetry. Several models are used to
      compute the emitted radiation, which are then compared with experimental data.
      Numerical results show that shock waves are absent in the stable SL regime, and
      compressional waves are already strong enough to produce moderate temperature and
      ionization. The degrees of ionization at the bubble center are found to be within
      7% to 30%, and Ar+ is the only dominant ion. Moreover, an opacity-corrected
      blackbody radiation model gives the peak power, pulse widths, and spectra that
      agree very well with the experimental data.

PMID- 12005811
TI  - Evaluation of effective ion-ion potentials in aqueous electrolytes.
AB  - We present high-accuracy simulation data for ion-ion radial distribution
      functions in NaCl aqueous electrolyte. From the data we evaluate ion-ion
      effective potentials via inverse Monte Carlo simulation procedure. Alternatively,
      we first evaluate effective direct correlation functions and then obtain
      effective potentials using the hypernetted-chain (HNC) approximation. Both
      methods are in excellent agreement, indicating that HNC approximation performs
      well with effective ion-ion potentials in aqueous solutions.

PMID- 12005812
TI  - Force evaluation in the lattice Boltzmann method involving curved geometry.
AB  - The present work investigates two approaches for force evaluation in the lattice
      Boltzmann equation: the momentum-exchange method and the stress-integration
      method on the surface of a body. The boundary condition for the particle
      distribution functions on curved geometries is handled with second-order accuracy
      based on our recent works [Mei et al., J. Comput. Phys. 155, 307 (1999); ibid.
      161, 680 (2000)]. The stress-integration method is computationally laborious for
      two-dimensional flows and in general difficult to implement for three-dimensional
      flows, while the momentum-exchange method is reliable, accurate, and easy to
      implement for both two-dimensional and three-dimensional flows. Several test
      cases are selected to evaluate the present methods, including: (i) two
      dimensional pressure-driven channel flow; (ii) two-dimensional uniform flow past
      a column of cylinders; (iii) two-dimensional flow past a cylinder asymmetrically
      placed in a channel (with vortex shedding); (iv) three-dimensional pressure
      driven flow in a circular pipe; and (v) three-dimensional flow past a sphere. The
      drag evaluated by using the momentum-exchange method agrees well with the exact
      or other published results.

PMID- 12005813
TI  - Heat transfer in the transition regime: solution of boundary value problems for
      Grad's moment equations via kinetic schemes.
AB  - This paper presents a systematic approach to the calculation of heat transfer in
      rarefied gases (Knudsen numbers between 0.01 and 1) by means of Grad's moment
      method with high moment numbers, based on the Boltzmann equation with linearized
      collision term. The problem of describing boundary conditions for the moments is
      solved by the use of the so-called kinetic schemes that allow the implementation
      of the boundary condition for the Boltzmann equation. The results, obtained with
      up to 48 one-dimensional moment equations, exhibit temperature jumps at the walls
      with adjacent Knudsen boundary layers. For given wall temperatures and Knudsen
      number, the results change with the number of moments, and converge if the number
      of moments is increased.

PMID- 12005814
TI  - Dynamics and configurational entropy in the Lewis-Wahnstrom model for supercooled
      orthoterphenyl.
AB  - We study thermodynamic and dynamic properties of a rigid model of the fragile
      glass-forming liquid orthoterphenyl. This model, introduced by Lewis and
      Wahnstrom in 1993, collapses each phenyl ring to a single interaction site; the
      intermolecular site-site interactions are described by the Lennard-Jones
      potential whose parameters have been selected to reproduce some bulk properties
      of the orthoterphenyl molecule. A system of N=343 molecules is considered in a
      wide range of densities and temperatures, reaching simulation times up to 1
      micros. Such long trajectories allow us to equilibrate the system at temperatures
      below the mode coupling temperature T(c) at which the diffusion constant reaches
      values of order 10(-10) cm(2)/s and thereby to sample in a significant way the
      potential energy landscape in the entire temperature range. Working within the
      inherent structures thermodynamic formalism, we present results for the
      temperature and density dependence of the number, depth and shape of the basins
      of the potential energy surface. We evaluate the total entropy of the system by
      thermodynamic integration from the ideal-noninteracting-gas state and the
      vibrational entropy approximating the basin free energy with the free energy of
      6N-3 harmonic oscillators. We evaluate the configurational part of the entropy as
      a difference between these two contributions. We study the connection between
      thermodynamical and dynamical properties of the system. We confirm that the
      temperature dependence of the configurational entropy and of the diffusion
      constant, as well as the inverse of the characteristic structural relaxation
      time, are strongly connected in supercooled states; we demonstrate that this
      connection is well represented by the Adam-Gibbs relation, stating a linear
      relation between logD and the quantity 1/TS(c). This relation is found to hold
      both above and below the critical temperature T(c)-as previously found in the
      case of silica-supporting the hypothesis that a connection exists between the
      number of basins and the connectivity properties of the potential energy surface.

PMID- 12005815
TI  - Frictional properties of bidisperse granular matter: effect of mixing ratio.
AB  - The frictional response of granular binary mixtures to an applied shear stress is
      studied experimentally by sliding a rough plate across a granular surface. The
      static friction force is found to be up to 25% larger than a linear interpolation
      between the frictional properties of each component. The dynamical friction
      coefficient can exhibit a maximum, a minimum, or an oscillatory behavior as a
      function of mixing ratio, depending on the size ratio or shape of the two
      components. In addition, visualization of the granular flow makes it possible to
      show that the shear layer thickness and the characteristic shear displacement,
      over which a steady state dilation is reached, change linearly with the mass
      concentration.

PMID- 12005816
TI  - Voronoi tessellation of the packing of fine uniform spheres.
AB  - The packing of uniform fine spherical particles ranging from 1 to 1000 microm has
      been simulated by means of discrete particle simulation. The packing structure is
      analyzed, facilitated by the well established Voronoi tessellation. The
      topological and metric properties of Voronoi polyhedra are quantified as a
      function of particle size and packing density. The results show that as particle
      size or packing density decreases, (i) the average face number of Voronoi
      polyhedra decreases, and the distributions of face number and edge number become
      broader and more asymmetric; (ii) the average perimeter and area of polyhedra
      increase, and the distributions of polyhedron surface area and volume become more
      flat and can be described by the log-normal distribution. The topological and
      metric properties depicted for the packing of fine particles differ either
      quantitatively or qualitatively from those reported in the literature although
      they all can be related to packing density. In particular, our results show that
      the average sphericity coefficient of Voronoi polyhedra varies with packing
      density, and although Aboav-Weaire's law is generally applicable, Lewis's law is
      not valid when packing density is low, which are contrary to the previous
      findings for other packing systems.

PMID- 12005817
TI  - Thermodynamic limit in the elastic triangle: Pade approximants.
AB  - The equilibrium properties of a triangular pile of N rows of particles,
      interconnected by linear springs and subjected to gravity are explored. A
      preliminary algebraic investigation of the small N value case suggests that the
      particle displacement field can be represented by low order Pade approximants.
      [1,1] Pade approximant representations are introduced for the horizontal and
      vertical displacement field components. Each representation contains three
      polynomials in the particle position coordinates. In the vertical displacement
      case the polynomials are successfully fitted to numerical solutions of the
      equilibrium equations. The resulting expression exhibits a thermodynamic limit
      with 1/N corrections. This procedure fails in the horizontal case. It is
      suspected that a higher order Pade approximant is required.

PMID- 12005818
TI  - Time evolution of dynamic shear moduli in a physical gelation process of 1,3:2,4
      bis-O-(p-methylbenzylidene)-D-sorbitol in polystyrene melt: critical exponent and
      gel strength.
AB  - We investigated time evolution of shear moduli in the physical gelation process
      of 1,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol (PDTS) in the polystyrene melt
      system containing 2.5 wt % of PDTS. At the gel point, storage and loss shear
      moduli, G' and G", were described by the power law of frequency omega, G'
      approximately G" approximately omega(n), with the critical exponent n equal to 2
      / 3, in agreement with the value predicted by the percolation theory. The
      exponent n and the gel strength S at the gel point measured as a function of
      quench depth DeltaT indicated that the fractal network structure of PDTS does not
      change with DeltaT but that the mechanical strength of the network increases with
      DeltaT. Before reaching the gel point, G'(omega) and G"(omega) obtained at
      various times can be well superposed onto the master curves, indicating that the
      mechanical as well as structural self-similarity hold in this gelation process.

PMID- 12005819
TI  - Transport of solutes undergoing a Freundlich type nonlinear and nonequilibrium
      adsorption process.
AB  - We investigate the behavior of solutes undergoing nonequilibrium adsorption
      processes that lead to a Freundlich isotherm in equilibrium. In contrast to a
      frequently used model we do not assume that the adsorption rate is proportional
      to the difference between adsorbed and equilibrium concentrations, but inspect
      two nonlinear laws governing the path to equilibrium. With some asymptotic
      considerations and numerical simulations we find that depending on the model
      parameters, the concentration in solution and the mass adsorbed by the matrix do
      not necessarily reach quasiequilibrium.

PMID- 12005820
TI  - Dangling bond deflection model: growth of gel network with loop structure.
AB  - It has been shown that the closed-loop structure in the model gel networks is
      responsible for their stiffness. However, the creation of loops has been
      underestimated in most of the existing kinetic aggregation models [e.g., DLCA
      (diffusion-limited cluster-cluster aggregation) and derivatives]. A dangling bond
      deflection (DEF) mechanism is proposed to model the fluctuation of dangling
      branches or dead ends under thermal excitation. The random deflections of the
      dangling branches can create loops in the network by forming intracluster bonds,
      and proceed during both the gelling and aging processes. The resulting DLCADEF
      networks have extensive loop structure with a negligible number of dangling
      branches. Its growth kinetics and fractal behavior resemble those of real gels,
      including volume-invariant gel time and fractal dimension of about 2. The DLCADEF
      model is the first attempt to model the gel growth with loop formation by the
      physically realistic fluctuation mechanism. The mechanical properties of the
      resulting networks will be studied and verified by comparison with real gels.

PMID- 12005821
TI  - Dynamic light scattering from colloidal fractal monolayers.
AB  - We address experimentally the problem of how the structure of a surface monolayer
      determines the viscoelasticity of the interface. Optical microscopy and surface
      quasielastic light scattering have been used to characterize aggregation of CaCO3
      particles at the air-water interface. The structures formed by cluster-cluster
      aggregation are two-dimensional fractals that grow to eventually form a
      percolating network. This process is measured through image analysis. On the same
      system we measure the dynamics of interfacial thermal fluctuations (surface
      ripplons), and we discuss how the relaxation process is affected by the growing
      clusters. We show that the structures start damping the ripplons strongly when
      the two length scales are comparable. No macroscopic surface pressure is measured
      and this is in contrast to lipid, surfactant, or polymer monolayers at
      concentrations corresponding to surface coverage. This observation and the
      difficulty in fitting the ripplon spectrum with traditional models suggest that a
      different physical mechanism might be responsible for the observed damping of
      ripplons in this system.

PMID- 12005822
TI  - Nature of the divergence in low shear viscosity of colloidal hard-sphere
      dispersions.
AB  - Measurements of the low-shear viscosity eta(o) with a Zimm-Crothers viscometer
      for dispersions of colloidal hard spheres are reported as a function of volume
      fraction phi up to 0.56. Nonequilibrium theories based on solutions to the two
      particle Smoluchoski equation or ideal mode coupling approximations do not
      capture the divergence. However, the nonhydrodynamic contribution to the relative
      viscosity Deltaeta(o) is correlated over a wide range of volume fractions by the
      Doolittle and Adam-Gibbs equations, indicating an exponential divergence at
      phi(m)=0.625+/-0.015. The data extend the previously proposed master curve,
      providing a test for improved theories for the many-body thermodynamic and
      hydrodynamic interactions that determine the viscosity of hard-sphere
      dispersions.

PMID- 12005823
TI  - Self-assembling morphology induced by nanoscale rods in a phase-separating
      mixture.
AB  - A symmetric binary mixture containing mobile nanoscale rods is quenched from a
      one-phase state into an unstable phase-separating region. Incorporating the
      motion of rods, the system undergoes spinodal decomposition to form a dropletlike
      structure. The rod-rod interaction and the preferential adsorption of one of the
      two immiscible phases onto the mobile rods play an important role in driving the
      system to self-assemble into this special structure. Within each cluster of the
      wetting phase, the rods align parallel to each other as in a nematic liquid
      crystal, while the rod orientations between these clusters are randomly
      distributed. However, an interconnected structure is recovered in the presence of
      hydrodynamic interaction. In the present phase-separating mixture with rods, the
      growth dynamics is examined in detail, and our simulations reveal a crossover
      from a rod-mobility-dependent to an independent regime. The system always
      exhibits slowing-down growth behavior where the well-known diffusive Lifshitz
      Slyozov mechanism and hydrodynamic effects are both suppressed.

PMID- 12005824
TI  - Transitions between inherent structures in water.
AB  - The energy landscape approach has been useful to help understand the dynamic
      properties of supercooled liquids and the connection between these properties and
      thermodynamics. The analysis in numerical models of the inherent structure (IS)
      trajectories-the set of local minima visited by the liquid-offers the possibility
      of filtering out the vibrational component of the motion of the system on the
      potential energy surface and thereby resolving the slow structural component more
      efficiently. Here we report an analysis of an IS trajectory for a widely studied
      water model, focusing on the changes in hydrogen bond connectivity that give rise
      to many IS's separated by relatively small energy barriers. We find that while
      the system travels through these IS's, the structure of the bond network is
      continuously modified, exchanging linear bonds for bifurcated bonds and usually
      reversing the exchange to return to nearly the same initial configuration. For
      the 216-molecule system we investigate, the time scale of these transitions is as
      small as the simulation time scale ( approximately 1 fs). Hence, for water, the
      transition between each of these IS's is relatively small and eventual relaxation
      of the system occurs only by many of these transitions. We find that during IS
      changes the molecules with the greatest displacements move in small "clusters" of
      1-10 molecules with displacements of approximately 0.02-0.2 nm, not unlike
      simpler liquids. However, for water these clusters appear to be somewhat more
      branched than the linear "stringlike" clusters formed in a supercooled Lennard
      Jones system found by Glotzer and her collaborators.

PMID- 12005825
TI  - Idealized glass transitions for a system of dumbbell molecules.
AB  - The mode-coupling theory for ideal glass transitions in simple systems is
      generalized to a theory for the glassy dynamics of molecular liquids using the
      density fluctuations of the sites of the molecule's constituent atoms as the
      basic structure variables. The theory is applied to calculate the liquid-glass
      phase diagram and the form factors for the arrested structure of a system of
      symmetric dumbbells of fused hard spheres. The static structure factors, which
      enter the equations of motion as input, are calculated as function of the packing
      fraction phi and the molecule's elongation zeta within the reference-interaction
      site-model and Percus-Yevick theories. The critical packing fraction phi(c) for
      the glass transition is obtained as nonmonotone function of zeta with a maximum
      near zeta=0.43. A transition line is calculated separating a small-zeta-glass
      phase with ergodic dipole motion from a large-zeta-glass phase where also the
      reorientational motion is arrested. The Debye-Waller factors at the transition
      are found to be somewhat larger for sufficiently elongated systems than those for
      the simple hard-sphere system, but the wave-number dependence of the glass-form
      factors is quite similar. The dipole reorientations for zeta> or =0.6 are
      arrested as strongly as density fluctuations with wave vectors at the position of
      the first sharp diffraction peak.

PMID- 12005826
TI  - Spatially resolved microrheology using localized coherence volumes.
AB  - We propose an optical technique, based on dynamic light scattering, for
      investigating the local rheological response of a complex fluid over a frequency
      range larger than that provided by standard mechanical instrumentation. The low
      coherence radiation used in a fiber optics configuration allows the measurements
      to be confined to a small volume around a tenth of a picoliter. The ability of
      the method to accurately measure both loss and storage moduli has been tested
      using both simple Newtonian liquids and viscoelastic, complex fluids. The
      possibility to monitor liquid-gel transitions in polymer solutions has also been
      demonstrated. The unique capability of the technique to localize the measurement
      volume suggests that this novel approach can be used for three-dimensional
      mapping of rheological properties in heterogeneous systems.

PMID- 12005827
TI  - Normal stresses at the gelation transition.
AB  - A simple Rouse-type model, generalized to incorporate the effects of chemical
      cross-links, is used to obtain a theoretical prediction for the critical behavior
      of the normal-stress coefficients Psi(1) and Psi(2) in polymeric liquids when
      approaching the gelation transition from the sol side. While the exact
      calculation shows Psi(2) identical with 0, a typical result for these types of
      models, an additional scaling ansatz is used to demonstrate that Psi(1) diverges
      with a critical exponent l=k+z. Here, k denotes the critical exponent of the
      shear viscosity and z the exponent governing the divergence of the time scale in
      the Kohlrausch decay of the shear-stress relaxation function. For cross-links
      distributed according to mean-field percolation, this scaling relation yields
      l=3, in accordance with an exact expression for the first normal-stress
      coefficient based on a replica calculation. Alternatively, using three
      dimensional percolation for the cross-link ensemble we find the value l
      approximately 4.9. Results on time-dependent normal-stress response are also
      presented.

PMID- 12005828
TI  - Model for the rotational contribution to quasielastic neutron scattering spectra
      from supercooled water.
AB  - A model is proposed for the first-, second-, and third-order rotational
      correlation functions that are required for the computation of the rotational
      intermediate scattering function for the calculation of incoherent quasielastic
      neutron scattering (QENS) spectra from supercooled water. The model is tested
      against molecular-dynamics data generated from an extended-simple-point-charge
      model of water and is found to be satisfactory. The model can be used as a
      practical method for extracting rotational relaxation parameters from QENS
      spectra measured at large Q from supercooled bulk water or interfacial water in
      porous materials.

PMID- 12005829
TI  - Ion-exchange funneling in thin-film coating modification of heterogeneous
      electrodialysis membranes.
AB  - Inexpensive highly permselective heterogeneous ion-exchange membranes are
      prohibitively highly polarizable by a dc current for being used in
      electrodialysis. According to recent experiments, polarizability of these
      membranes may be considerably reduced by casting on their surface a thin layer of
      crosslinked polyelectrolyte, slightly charged with the same sign as the
      membrane's charge. The present paper is concerned with this effect. Concentration
      polarization of a permselective heterogeneous ion-exchange membrane by a dc
      current is determined by geometric factors, such as, the typical size of the ion
      permeable "gates" at the membrane surface relative to the separation distance
      between them and the diffusion layer thickness. The main quantitative
      characteristic of polarizability of a heterogeneous membrane is its
      voltage/current curve with its typical saturation at the limiting current, which
      is lower than that for a homogeneous membrane. In the present study we modify the
      previously developed two-dimensional model of ionic transport in a diffusion
      layer at a heterogeneous ion-exchange membrane by including into consideration a
      homogeneous ion-exchange layer adjacent to the membrane surface. A numerical
      solution of the respective boundary value problem shows that, indeed, adding even
      a very thin and weakly charged layer of this kind increases the value of the
      limiting current, to that of a homogeneous membrane. What differs, for different
      values of coating parameters, is the form of the voltage/current curves but not
      the value of the limiting current, namely: the thinner is the coating and the
      lower the fixed charge density in it, the "slower" is the approach of the
      limiting current. In order to explain this feature, a simple limiting model of
      modified membrane is derived from the original two-layer model. In this limiting
      model, asymptotically valid for a thin coating, solution of the ionic transport
      equations in it is replaced, via a suitable averaging procedure, by a single
      nonlinear boundary condition for the membrane/solution interface. Rigorous
      analysis shows that the aforementioned property of the limiting current is an
      exact mathematical feature of this limiting model, when the underlying physical
      phenomenon is the funneling of counterions by the charged layer from the
      impermeable parts of the membrane towards the "entrance gates." An approximate
      analytical solution, developed for this model, compares well with the exact
      numerical one.

PMID- 12005830
TI  - Anisotropic ordering in sheared binary fluids with viscous asymmetry: experiment
      and computer simulation.
AB  - Optical measurements of the structure and morphology of phase-separating polymer
      blend under simple shear flow have been performed and the results are compared
      with computer simulations of sheared phase-separating binary mixtures with
      viscous asymmetry in the fluid components. Information about the structure is
      obtained from the two-point composition correlation function. Both experiment and
      simulation suggest subtle differences in the shear response depending on whether
      the more viscous phase is dispersed or continuous. Measurements of the string
      width along the neutral direction suggest power-law decay in the shear rate with
      an exponent of 1/3 when the more viscous phase is dispersed. The simulations
      suggest that the mean string width, measured along the velocity-gradient
      direction in the two-dimensional model calculation, exhibits power-law decay in
      the shear rate with an exponent of 1/3 independent of which phase is dispersed.

PMID- 12005831
TI  - Statistical substantiation of the van der Waals theory of inhomogeneous fluids.
AB  - Computer experiments on simulation of thermodynamic properties and structural
      characteristics of a Lennard-Jones fluid in one- and two-phase models have been
      performed for the purpose of checking the base concepts of the van der Waals
      theory. Calculations have been performed by the method of molecular dynamics at
      cutoff radii of the intermolecular potential r(c,1)=2.6sigma and
      r(c,2)=6.78sigma. The phase equilibrium parameters, surface tension, and density
      distribution have been determined in a two-phase model with a flat liquid-vapor
      interface. The strong dependence of these properties on the value of r(c) is
      shown. The p,rho,T properties and correlation functions have been calculated in a
      homogeneous model for a stable and a metastable fluid. An equation of state for a
      Lennard-Jones fluid describing stable, metastable, and labile regions has been
      built. It is shown that at T > or =1.1 the properties of a flat interface within
      the computer experimental error can be described by the van der Waals square
      gradient theory with an influence parameter kappa independent of the density.
      Taking into account the density dependence of kappa through the second moment of
      the direct correlation function will deteriorate the agreement of the theory with
      data of computer simulation. The contribution of terms of a higher order than
      (nablarho)(2) to the Helmholtz free energy of an inhomogeneous system has been
      considered. It is shown that taking into account terms proportional to
      (nablarho)(4) leaves no way of obtaining agreement between the theory and
      simulation data, while taking into consideration of terms proportional to
      (nablarho)(6) makes it possible to describe with adequate accuracy all the
      properties of a flat interface in the temperature range from the triple to the
      critical point.

PMID- 12005832
TI  - Decoration lattices of colloids adsorbed on stripe-patterned substrates.
AB  - The equilibrium structure of decoration lattices composed of colloidal particles
      adsorbed on periodic stripe-patterned substrates is calculated as a function of
      the stripe width and separation and for different interparticle interactions. Due
      to a competition of length scales, a wealth of different stable decoration
      lattices occurs such as triangular, quadratic, rhombic, kitelike, and sheared
      honeycomb lattices, triangular slices as well as triangle superlattices. This is
      of relevance for constructing templates that enforce crystal growth of unusual
      solid structures.

PMID- 12005833
TI  - Cavitation of Langmuir monolayers.
AB  - Cavitation in liquid expanded and liquid condensed Langmuir monolayers induced by
      laser heating or microbubble coalescence is studied experimentally using
      fluorescence and Brewster angle microscopy. The kinetics of hole closure of two
      dimensional (2D) gaseous cavitation bubbles exhibits a decelerated dynamics for
      cavities surrounded by a liquid expanded phase and an accelerated dynamics for
      cavities in a liquid condensed phase. Most of the cavities in liquid condensed
      phases possess a nonconvex shape and do not close. The results are compared with
      theoretical predictions derived for 2D cavitation of liquid monolayers of
      different surface shear viscosities, and for solid monolayers with diffusive flux
      of vacancies and interstitials. While part of the theory is in qualitative
      agreement with the experiment, the experimentally observed hole persistence
      within the liquid condensed phases and the hole closure within liquid expanded
      phases remains to be explained. The technique of microbubble coalescence might be
      particularly useful for the study of the rheological properties of hexatic
      phases.

PMID- 12005834
TI  - Singular self-preserving regimes of coagulation processes.
AB  - The late stages of the time evolution of disperse systems when either coagulation
      alone governs the temporal changes of particle mass spectra or simultaneous
      condensation complicates the evolution process are studied under the assumption
      that the condensation efficiencies and coagulation kernels are homogeneous
      functions of the particle masses, with gamma and lambda being their homogeneity
      exponents, respectively. In considering the asymptotic behavior of the particle
      mass distributions the renormalization-group approach is applied to three types
      of coagulating systems: free coagulating systems in which coagulation alone is
      responsible for disperse particle growth; source-enhanced coagulating systems,
      where an external spacially uniform source permanently adds fresh small
      particles, with the particle production being a power function of time; and
      coagulating-condensing systems in which a condensation process accompanies the
      coagulation growth of disperse particles. The particle mass distributions of the
      form N(A)(g,t)=A(t)psi(gB(t)) are shown to describe the asymptotic regimes of
      particle growth in all the three types of coagulating systems (g is the particle
      mass). The functions A(t) and B(t) are normally power functions of time whose
      power exponents are found for all possible regimes of coagulation and
      condensation as the functions of lambda and gamma. The equations for the
      universality function psi(x) are formulated. It is shown that in many cases
      psi(x) proportional, variant x(-sigma) (sigma > 1) at small x, i.e., the particle
      mass distributions are singular. The power exponent sigma is expressed in terms
      of lambda and gamma. Two exactly soluble models illustrate the general
      theoretical consideration.

PMID- 12005835
TI  - Measuring kinetic coefficients by molecular dynamics simulation of zone melting.
AB  - Molecular dynamics simulations are performed to measure the kinetic coefficient
      at the solid-liquid interface in pure gold. Results are obtained for the (111),
      (100), and (110) orientations. Both Au(100) and Au(110) are in reasonable
      agreement with the law proposed for collision-limited growth. For Au(111),
      stacking fault domains form, as first reported by Burke, Broughton, and Gilmer
      [J. Chem. Phys. 89, 1030 (1988)]. The consequence on the kinetics of this
      interface is dramatic: the measured kinetic coefficient is three times smaller
      than that predicted by collision-limited growth. Finally, crystallization and
      melting are found to be always asymmetrical and here again the effect is much
      more pronounced for the (111) orientation.

PMID- 12005836
TI  - Interface relaxation in electrophoretic deposition of polymer chains: effects of
      segmental dynamics, molecular weight, and field.
AB  - Using different segmental dynamics and relaxation, characteristics of the
      interface growth is examined in an electrophoretic deposition of polymer chains
      on a three (2+1)-dimensional discrete lattice with a Monte Carlo simulation.
      Incorporation of faster modes such as crankshaft and reptation movements along
      with the relatively slow kink-jump dynamics seems crucial in relaxing the
      interface width. As the continuously released polymer chains are driven (via
      segmental movements) and deposited, the interface width W grows with the number
      of time steps t, W proportional, variant t(beta), (beta approximately 0.4-0.8),
      which is followed by its saturation to a steady-state value W(s). Stopping the
      release of additional chains after saturation while continuing the segmental
      movements relaxes the saturated width to an equilibrium value (W(s)-->W(r)).
      Scaling of the relaxed interface width W(r) with the driving field E, W(r)
      proportional, variant E(-1/2) remains similar to that of the steady-state W(s)
      width. In contrast to monotonic increase of the steady-state width W(s), the
      relaxed interface width W(r) is found to decay (possibly as a stretched
      exponential) with the molecular weight.

PMID- 12005837
TI  - Experimental investigation of the initial regime in fingering electrodeposition:
      dispersion relation and velocity measurements.
AB  - Recently a fingering morphology, resembling the hydrodynamic Saffman-Taylor
      instability, was identified in the quasi-two-dimensional electrodeposition of
      copper. We present here measurements of the dispersion relation of the growing
      front. The instability is accompanied by gravity-driven convection rolls at the
      electrodes, which are examined using particle image velocimetry. While at the
      anode the theory presented by Chazalviel et al. [J. Electroanal. Chem. 407, 61
      (1996)] describes the convection roll, the flow field at the cathode is more
      complicated because of the growing deposit. In particular, the analysis of the
      orientation of the velocity vectors reveals some lag of the development of the
      convection roll compared to the finger envelope.

PMID- 12005838
TI  - Stability analysis of branched silver electrodeposits: solid phase growth under a
      marginally stable regime.
AB  - The mass-transport controlled growth of silver deposits at the early stage of
      multiple bump formation, and when a silver single needle growth regime is
      attained, are investigated. Linear stability analysis as proposed by Barkey,
      Muller, and Tobias [J. Electrochem. Soc. 136, 2199 (1989)] is applied to kinetic
      mesoscale data. A reasonable correlation between the current density and the
      average amplitude of unstable perturbation is established.

PMID- 12005839
TI  - Relaxation of particles in the sloped region in a conserved growth model.
AB  - The dynamical scaling properties of conserved growth models, in which the
      downward (upward) movement of a particle dropped only on the sloped region occurs
      with a probability p (1-p), are investigated by simulations in the substrate
      dimension d=1. By direct analysis of the surface fluctuation W, the models with
      p>1/2 are clearly and cleanly shown to have crossover behavior from Mullins
      Herring (MH) universality to Edwards-Wilkinson (EW) universality. In contrast,
      the models with p<1/2 are shown to have an instability eventually, even though
      they initially follow the MH equation. The model with p=1/2 is shown to belong to
      the MH universality class and to be the critical model that splits the models
      with EW behavior from those with the instability. From these results we explain
      the physical reason for the very slow crossover in models like the Wolf-Villain
      model.

PMID- 12005840
TI  - Complex dynamics of isotropic 4-cyano-4-n-pentylbiphenyl (5CB) in linear and
      nonlinear dielectric relaxation studies.
AB  - A comprehensive presentation of the temperature evolution of "linear" and
      "nonlinear" dielectric relaxation in the isotropic phase of nematic liquid
      crystalline compound 5CB (4-cyano-4-n-pentylbiphenyl) is given. The "nonlinear"
      relaxation is related to the strong pretransitional rise in the lifetime of
      prenematic fluctuations. The "linear" relaxation has a clear non-Debye and non
      Arrhenius form. In the immediate vicinity of the nematic clearing point it shows
      a weak pretransitional anomaly. Results obtained coincide with the complex liquid
      relaxation pattern found in transient grating optical Kerr effect studies [A.
      Sengupta and M. D. Fayer, J. Chem. Phys. 102, 4193 (1995); R. Torre et al.,
      Philos. Mag. A 77, 645 (1997)]. The striking similarity to the behavior found in
      critical, binary mixtures suggests the extension of the "fluidlike" hypothesis
      for the isotropic-nematic transition to dynamic phenomena in the isotropic phase
      [P. K. Mukherjee. J. Phys.: Condens. Matter 10, 9191 (1998)]. The presence of
      both glassy and fluidlike features in isotropic 5CB coincides with the recent
      results of simulation analysis for the system of hard ellipsoids by Latz et al.
      [Phys. Rev. E 62, 5173 (2000)] and with the novel general picture for liquid
      liquid transitions proposed by Tanaka [Phys. Rev. E 62, 6968 (2000)].

PMID- 12005841
TI  - Defect structures and torque on an elongated colloidal particle immersed in a
      liquid crystal host.
AB  - Combining molecular dynamics and Monte Carlo simulation, we study defect
      structures around an elongated colloidal particle embedded in a nematic liquid
      crystal host. By studying nematic ordering near the particle and the disclination
      core region, we are able to examine the defect core structure and the difference
      between two simulation techniques. In addition, we also study the torque on a
      particle tilted with respect to the director, and modification of this torque
      when the particle is close to the cell wall.

PMID- 12005842
TI  - Behavior of mesogenic molecules deposited at the alumina-air interface: a
      deuteron NMR study.
AB  - Thin molecular depositions of 4(')-pentyl-4-cyonobiphenyl (5CB) mesogenic
      molecules are investigated via quadrupole-perturbed deuteron nuclear magnetic
      resonance (DNMR) spectroscopy. Uniform and controlled thickness molecular surface
      depositions are prepared on the inner cylindrical surfaces of Anopore membranes
      by the solvent-evaporation technique. As a result, 5CB molecules are found in two
      different configurations: a bulklike one with parallel axial arrangement, and a
      surface one with planar radial arrangement. If the 5CB surface coverage exceeds c
      approximately 0.35, only the bulk state is present. In the coverage range between
      0.015 and 0.35, the bulklike state and the surface layer coexist, conforming to a
      typical dewetting scenario. Below c approximately 0.015, only the surface layer
      is present. The dilution of the surface deposition with decreasing coverage is
      manifested as an increase in the DNMR doublet frequency splitting. The surface
      orientational order parameter Q, the surface biaxiality eta, and the diffusion
      coefficient D(S) are determined from the DNMR spectral patterns obtained at
      different sample orientations in the external magnetic field. These angular
      patterns prove that in highly diluted surface depositions the molecules lie flat
      on the surface. However, they are not frozen and their molecular axes rapidly
      reorient on the DNMR measurement time scale, typically 10(-4) s, while remaining
      confined to the surface. Simultaneously, molecules diffuse over the surface with
      a surface diffusion constant on the order of 10(-11) m(2) s(-1). Such molecular
      diffusion is responsible for an effective biaxiality on the DNMR time scale.
      However, an inherent biaxiality cannot be completely ruled out and thus may play
      a minor role. The surface phase has a two-dimensional (2D) gas character with
      some (possible) indicators of 2D-liquid properties.

PMID- 12005843
TI  - Nonlinear dielectric spectroscopy in the smectic-A-smectic-C(*)(alpha) phase
      transition.
AB  - We performed nonlinear dielectric spectroscopy to study the dynamic properties
      near the smectic-A-smectic-C(*)(alpha) phase transition point of an
      antiferroelectric liquid crystal 4-(1-methyl-heptyloxycar- bonyl)phenyl 4
      octylcarbonyloxybiphenyl-4-carboxylate (MHPOCBC). A Landau-type theory was
      developed in order to analyze the experimentally obtained frequency dispersions.
      From the experimental and theoretical results we successfully obtained the
      temperature dependence of the relaxation frequency of the soft mode in both the
      smectic-A and smectic-C(*)(alpha) phases, which gave direct evidence that the
      transition is brought about by soft mode condensation. Significant features of
      this transition are also discussed.

PMID- 12005844
TI  - Interlayer structures of the chiral smectic liquid crystal phases revealed by
      resonant X-ray scattering.
AB  - The structures of the liquid crystalline chiral subphases exhibited by several
      materials containing either a selenium or sulphur atom have been investigated
      using a resonant x-ray scattering technique. This technique provides a unique
      structural probe for the ferroelectric, ferrielectric, antiferroelectric, and
      SmC(*)(alpha) phases. An analysis of the scattering features allows the
      structural models of the different subphases to be distinguished, in addition to
      providing a measurement of the helical pitch. This paper reports resonant
      scattering features in the antiferroelectric hexatic phase, the three- and four
      layer intermediate phases, the antiferroelectric and ferroelectric phases and the
      SmC(*)(alpha) phase. The helicoidal pitch has been measured from the scattering
      peaks in the four-layer intermediate phase as well as in the antiferroelectric
      and ferroelectric phases. In the SmC(*)(alpha) phase, an investigation into the
      helical structure has revealed a pitch ranging from 5 to 54 layers in different
      materials. Further, a strong resonant scattering signal has been observed in
      mixtures of a selenium containing material with as much as 90% nonresonant
      material.

PMID- 12005845
TI  - Phase behavior and free interfaces of a lattice-gas nematic-liquid-crystal model.
AB  - The phase behavior of a mesogenic lattice-gas model consisting of molecules
      located at the sites of a three-dimensional cubic lattice has been studied using
      grand canonical Monte Carlo simulations. When two neighboring sites are occupied,
      the molecules interact via a potential composed of an isotropic lattice-gas (LG)
      term and an anisotropic Humphries-Luckhurst-Romano (HLR) term [Mol. Phys. 42,
      1205 (1981)]. The LGHLR model is shown to exhibit either nematic-isotropic,
      nematic-vapor (NV), and isotropic-vapor (IV) coexistence or just nematic
      isotropic fluid coexistence, depending on the strength of the isotropic term. The
      liquid-vapor (i.e., NV and IV) interfaces were studied using canonical Monte
      Carlo simulations. By controlling the strength of the term that governs the
      anisotropy in the attractive forces, either planar or homeotropic anchoring is
      observed at the NV interface. The temperature dependencies of the density and
      order parameter profiles across the interfaces are determined for these two
      anchoring geometries.

PMID- 12005846
TI  - Structure and elastic properties of smectic liquid crystalline elastomer films.
AB  - Mechanical measurements, x-ray investigations, and optical microscopy are
      employed to characterize the interplay of chemical composition, network topology,
      and elastic response of smectic liquid crystalline elastomers (LCEs) in various
      mesophases. Macroscopically ordered elastomer films of submicrometer thicknesses
      were prepared by cross linking freely suspended smectic polymer films. The cross
      linked material preserves the mesomorphism and phase transitions of the precursor
      polymer. The elastic response of the smectic LCE is entropic, and the
      corresponding elastic moduli are of the order of MPa. In the tilted ferroelectric
      smectic-C* phase, the network structure plays an important role. Due to the
      coupling of elastic network deformations to the orientation of the mesogenic
      groups in interlayer cross-linked materials (mesogenic cross-linker units), the
      stress-strain characteristics is found to differ qualitatively from that in the
      other phases.

PMID- 12005847
TI  - Coil-globule transition for regular, random, and specially designed copolymers:
      Monte Carlo simulation and self-consistent field theory.
AB  - The coil-globule transition has been studied for A-B copolymer chains both by
      means of lattice Monte Carlo (MC) simulations using bond fluctuation algorithm
      and by a numerical self-consistent-field (SCF) method. Copolymer chains of fixed
      length with A and B monomeric units with regular, random, and specially designed
      (proteinlike) primary sequences have been investigated. The dependence of the
      transition temperature on the AB sequence has been analyzed. A proteinlike
      copolymer is more stable than a copolymer with statistically random sequence. The
      transition is more sharp for random copolymers. It is found that there exists a
      temperature below which the chain appears to be in the lowest energy state
      (ground state). Both for random and proteinlike sequences and for regular
      copolymers with a relatively long repeating block, a molten globule regime is
      found between the ground state temperature and the transition temperature. For
      regular block copolymers the transition temperature increases with block size.
      Qualitatively, the results from both methods are in agreement. Differences
      between the methods result from approximations in the SCF theory and
      equilibration problems in MC simulations. The two methods are thus complementary.

PMID- 12005848
TI  - Defect structure of a nematic liquid crystal around a spherical particle:
      adaptive mesh refinement approach.
AB  - We investigate numerically the structure of topological defects close to a
      spherical particle immersed in a uniformly aligned nematic liquid crystal. To
      this end we have implemented an adaptive mesh refinement scheme in an axi
      symmetric three-dimensional system, which makes it feasible to take into account
      properly the large length scale difference between the particle and the
      topological defects. The adaptive mesh refinement scheme proves to be quite
      efficient and useful in the investigation of not only the macroscopic properties
      such as the defect position but also the fine structure of defects. It can be
      shown that a hyperbolic hedgehog that accompanies a particle with strong
      homeotropic anchoring takes the structure of a ring.

PMID- 12005849
TI  - Statistical theory of the compensating effect when anchoring with two orthogonal
      photoaligned polymers.
AB  - In this paper we extend a statistical microscopic analysis to the anchoring
      properties of polymer films obtained by two concomitant or subsequent
      polymerization processes along two different directions. We can thus explain the
      recently observed compensating effect of two orthogonal polymerization processes.
      An expression for the anchoring energy has been evaluated from the extra
      Helmholtz free energy within an interface layer where the interactions shift from
      polymer-nematic interactions to nematic-nematic interactions, as in bulk. The
      result includes the angular dependence on the two photoaligning directions. A
      procedure of getting controlled anchoring strength in situ is suggested.

PMID- 12005850
TI  - Annihilation of point defects on a line.
AB  - We discuss the evolution of the distribution function of distances between point
      defects of opposite signs distributed on a line of finite length interacting via
      a potential attractive at short distances and repulsive at large distances. The
      standard deviation of the distribution grows quickly at short times, attains
      maximum, and decreases logarithmicaly at longer times. The distance between the
      defects increases monotonically and at equilibrium is about two times larger than
      the distance at which the repulsive force attains maximum. The distance dependent
      viscosity does not change qualitatively these conclusions, but only increases the
      time scale of evolution by one order of magnitude.

PMID- 12005851
TI  - Dynamic light scattering measurements of azimuthal and zenithal anchoring of
      nematic liquid crystals.
AB  - Dynamic light scattering is used to obtain the anchoring energy coefficients of
      nematic liquid crystal (4-n-pentyl-4(')-cyanobiphenyl) on rubbed nylon and
      photoactive poly-(vinyl-cinnamate). The anchoring coefficients are determined by
      measuring the relaxation time of the fundamental director fluctuation mode in a
      homogeneously aligned wedge cell as a function of cell thickness. The method is
      nonperturbative as no external torque is applied to the liquid crystal during the
      measurement. We show that by using two different scattering geometries, both
      azimuthal and zenithal anchoring energy coefficients can be measured on the same
      sample. The obtained zenithal anchoring coefficient is found to be, in contrast
      to previously reported results, approximately only two times larger than the
      azimuthal one. The effect of higher order fluctuation modes on the detected
      autocorrelation function is in good agreement with numerical calculations.

PMID- 12005852
TI  - Nature of the liquid crystalline phase transitions in the cesium
      pentadecafluorooctanoate-water system: the nematic-to-smectic-A transition.
AB  - Measurements of the diamagnetic susceptibility chi(a), the rotational viscosity
      coefficient gamma(1), and the micellar orientational order parameter S have been
      made as a function of temperature across the entire nematic phases of cesium
      pentadecafluorooctanoate (CsPFO)-D2O samples over the concentration range weight
      fraction CsPFO w from 0.350 to 0.500. This has been chosen so as to embrace the
      pseudo-nematic phase-lamellar tricritical point that has been purported to occur
      at w=0.43 (volume fraction phi=0.26). The values of gamma(1) vary from about 0.1
      kg m(-1) s(-1) to 1000 kg m(-1) s(-1) as the temperature decreases across the
      nematic phase, covering a much larger range than those reported for thermotropic
      liquid crystals. Measurements of gamma(1) have been made much closer to the
      critical temperature T(LN) than have previously been reported [(T-T(LN))/T(LN)=2
      x 10(-5) for the w=0.350 sample]. The rotational viscosity critical exponents x
      calculated from the divergence of gamma(1) on approaching the nematic-phase-to
      lamellar transition are found to be constant at 2/3 independent of the
      concentration. These values differ from those of 1/3 and 1/2, respectively,
      predicted by the He-like three-dimensional XY and mean-field models, in
      combination with mean-field dynamical relaxation. However, the former would be
      supported if complete Fisher renormalization (at alpha=1/2) was appropriate over
      an extended concentration range. Alternatively, this could be an indication of
      the importance of coupling between the micellar rotational dynamics and critical
      fluctuations since the latter are seen to be predominant across the entire
      temperature range of the nematic phase as revealed in the temperature dependence
      of gamma(1).

PMID- 12005853
TI  - Orientational distributions in smectic liquid crystals showing V-shaped switching
      investigated by polarized Raman scattering.
AB  - Molecular orientational order parameters have been obtained by Raman scattering
      in two types of liquid crystal materials showing the V-shaped switching in thin
      homogeneous cells. One is the Mitsui mixture and the other is one component of
      the Inui mixture. The antiferroelectric phase exists in the bulk of both
      materials but, in thin homogeneous cells, the stability is distinct from each
      other. The obtained distribution of the local in-plane directors at the tip of
      the V is considerably broad in the former, while it is narrow in the latter.
      These differences have been explained by the barrier between the ferroelectric
      and antiferroelectric orderings, the chiral twisting power, and the interface
      induced destruction of the antiferroelectric ordering.

PMID- 12005854
TI  - Electronic transport in smectic liquid crystals.
AB  - Time-of-flight measurements of transient photoconductivity have revealed bipolar
      electronic transport in phenylnaphthalene and biphenyl liquid crystals (LC),
      which exhibit several smectic mesophases. In the phenylnaphthalene LC, the hole
      mobility is significantly higher than the electron mobility and exhibits
      different temperature and phase behavior. Electron mobility in the range
      approximately 10(-5) cm(2)/V s is temperature activated and remains continuous at
      the phase transitions. However, hole mobility is nearly temperature independent
      within the smectic phases, but is very sensitive to smectic order, 10(-3) cm(2)/V
      s in the smectic-B (Sm-B) and 10(-4) cm(2)/V s in the smectic-A (Sm-A)
      mesophases. The different behavior for holes and electron transport is due to
      differing transport mechanisms. The electron mobility is apparently controlled by
      rate-limiting multiple shallow trapping by impurities, but hole mobility is not.
      To explain the lack of temperature dependence for hole mobility within the
      smectic phases we consider two possible polaron transport mechanisms. The first
      mechanism is based on the hopping of Holstein small polarons in the nonadiabatic
      limit. The polaron binding energy and transfer integral values, obtained from the
      model fit, turned out to be sensitive to the molecular order in smectic
      mesophases. A second possible scenario for temperature-independent hole mobility
      involves the competion between two different polaron mechanisms involving so
      called nearly small molecular polarons and small lattice polarons. Although the
      extracted transfer integrals and binding energies are reasonable and consistent
      with the model assumptions, the limited temperature range of the various phases
      makes it difficult to distinguish between any of the models. In the biphenyl LCs
      both electron and hole mobilities exhibit temperature activated behavior in the
      range of 10(-5) cm(2)/V s without sensitivity to the molecular order. The
      dominating transport mechanism is considered as multiple trapping in the impurity
      sites. Temperature-activated mobility was treated within the disorder formalism,
      and activation energy and width of density of states have been calculated.

PMID- 12005855
TI  - Deuterium NMR relaxation in the smectic-A phase of a chiral smectogen.
AB  - Correlated internal rotations are studied for a deuterated decyloxy chain in the
      chiral liquid crystal, 1-methylheptyl 4(')-(4-n-decyloxy-benzoyloxy)biphenyl-4
      carboxyate (10B1M7) using deuteron spin-lattice relaxation and quadrupolar
      splitting measurements. The present study is limited to the uniaxial smectic-A
      phase of 10B1M7, in which the observed deuterium nuclear magnetic resonance
      spectra show well-resolved peaks. The deuteron Zeeman (T(1Z)) and quadrupolar
      (T(1Q)) spin-lattice relaxation times are simultaneously determined for the
      methylene deuterons using the Wimperis broadband pulse sequence at two different
      Larmor frequencies. The quadrupolar splittings at each temperature are modeled by
      the additive potential method to obtain the orienting potential of mean torque. A
      decoupled model using 683 conformations for the decyloxy chain is used to explain
      the observed relaxation rates. In this model, the overall reorientation is
      described by a small step rotational diffusion model, while both gauche migration
      and gauche pair production as well as the so called one- and two-bond motions are
      allowed to occur in the chain. Transition rates for the chain dynamics and the
      overall rotational diffusion constants are obtained using a global target
      analysis of the relaxation data of 10B1M7.

PMID- 12005856
TI  - Shear-induced structural changes of a smectic-A phase: a computer simulation
      study.
AB  - We have carried out a Monte Carlo simulation of a thin sample of the smectic-A
      phase of the Gay-Berne mesogen GB(4.4,20.0,1,1) sandwiched between two plates and
      subject to shear. The smectic layers are perpendicular to the confining plates
      and are pinned at the boundaries. The thickness of the samples studied ranges
      from about three to twenty molecules. The layers tilt progressively with
      increasing shear, but rearrange themselves at a critical shear. At this critical
      shear the layers melt near the center of the sample and reform with a reduced
      tilt consistent with the layer pinning at the walls. The pseudodynamics of this
      process as the smectic layers melt and are reformed have been followed during the
      simulation. The critical layer tilt at which slippage takes place tends to a
      constant value for thick samples, but for very thin samples the critical shear
      tends toward half a smectic layer, with a significantly reduced translational
      order near the sample center just before the critical shear. The simulation
      results are consistent with the predictions of the mean field theory of this
      phenomenon developed by Mottram et al.

PMID- 12005857
TI  - Disruption of surface-induced smectic order by periodic surface corrugations.
AB  - A Freedericksz transition measurement is reported for a liquid crystal cell
      composed of surfactant-coated substrates. One substrate was locally scribed with
      the stylus of an atomic force microscope to create a nanoscopic grooved
      structure. The Freedericksz threshold voltage was found to be smaller in the
      scribed region than in the unscribed region, indicating that the corrugated
      surface disrupts surface-induced smectic order, and that the effect grows toward
      the nematic-smectic-A transition temperature T(NA) in conjunction with the
      smectic correlation length.

PMID- 12005858
TI  - Photomanipulation of the anchoring strength of a photochromic nematic liquid
      crystal.
AB  - The behavior of the Freedericksz threshold voltage of a planarly oriented sample
      filled with liquid crystalline azobenzene material possessing a nematic phase is
      investigated under UV illumination. It is found that the anchoring strength
      strongly decreases with the UV-exposure time due to the photoisomerization
      process that takes place in the sample. The changes in the anchoring strength are
      due to a selective adsorption of cis isomers at the surface. We show that the
      experimental data can be explained by a model that takes into account the changes
      in the molecular shape and in the net molecular dipole moment due to the cis
      trans isomerization. We obtain a good agreement between the predictions of the
      model and the experimental data.

PMID- 12005859
TI  - UV manipulation of order and macroscopic shape in nematic elastomers.
AB  - A range of monodomain nematic liquid-crystal elastomers containing differing
      proportions of photoisomerizable mesogenic moieties, which turn from a rodlike to
      a kinked shape upon ultraviolet (uv) irradiation, was studied. Depending on the
      proportion and positional role of the photosensitive groups in the crosslinked
      polymer network, different types and magnitudes of response were found. The
      principle consequence of such photoisomerization is the destabilization of the
      nematic phase, whose order parameter depends on temperature in a near-critical
      fashion. Accordingly, the effect of uv irradiation is dramatically enhanced near
      the critical temperature, with the associated reduction in the nematic order
      parameter manifesting as a change in the macroscopic shape of the elastomer
      samples, producing a large uniaxial contraction. Theoretical analysis of this
      phenomenon gives a good quantitative agreement with experiment.

PMID- 12005860
TI  - Unwinding globules under tension and polymer collapse.
AB  - Polymer collapse is known to be mediated by the formation of pearls. These
      intermediate structures behave as small globules under tension. The globule size
      is studied by molecular dynamic simulations as a function of the strength of an
      external stretching force applied to its ends, for different values of the chain
      length. A very strong first-order-like transition from a compact globule state to
      a stretched one is observed. A model of this transition in terms of a globule
      chain system is presented. The critical force, above which the globule unwinds,
      is shown to satisfy a power law scaling like N(1/3) in the number of monomers.

PMID- 12005861
TI  - Determination of the structure of the organized phase of the block copolymer PEO
      PPO-PEO in aqueous solutions under flow by small-angle neutron scattering.
AB  - The organization of Tetronic 908 (T908), a star copolymer of poly(ethylene oxide)
      (PEO) and poly(propylene oxide) (PPO) blocks, has been examined. Above critical
      conditions of temperature and concentration, the micelles formed by the
      aggregation of PPO units self-organize into particular structures. While small
      angle neutron scattering (SANS) characterizations performed with static
      conditions demonstrate the organization of the medium, the experimental results
      do not allow us to make a distinction between simple cubic and body-centered
      cubic structures. However, SANS measurements realized under shear produce
      characteristic diffraction diagrams. In this paper, an accurate methodology is
      proposed to identify, without ambiguity, the exact nature of the organized phase.
      Applied to our system, indexing of the diffraction pattern spots reveals that the
      organization of T908 is of bcc type oriented with the [111] direction parallel to
      the direction of flow, but the crystals can present any orientation about this
      direction. The lattice size has been estimated and compared to previous published
      results.

PMID- 12005862
TI  - Elastic critical behavior in a three-dimensional model for polymer gels.
AB  - The elastic response in polymeric gels is studied by means of a percolation
      dynamic model. By numerical simulations the fluctuations in the gyration radius
      and in the center-of-mass motion of the percolating cluster are determined. Their
      scaling behavior at the gelation threshold gives a critical exponent for the
      elastic modulus f approximately 2.5+/-0.1 in agreement with the prediction f=dnu.

PMID- 12005863
TI  - Self-motion and the alpha relaxation in a simulated glass-forming polymer:
      crossover from Gaussian to non-Gaussian dynamic behavior.
AB  - We present fully atomistic molecular dynamics simulations for a realistic model
      of a glass-forming polymer: polyisoprene. The simulations are carried out at 363
      K and extend until 20 ns. We calculate the self-part of the Van Hove correlation
      function G(s)(r,t), the mean-squared displacement <r(2)(t)>, the second-order non
      Gaussian parameter alpha(2)(t), and the incoherent intermediate scattering
      function F(s)(Q,t) for the main chain protons. In addition, we also calculate the
      density-density correlation function F(Q,t)/F(Q,0) and the second-order
      autocorrelation function M2(t) for different C-H bonds of the main chain.
      alpha(2)(t) shows a broad maximum centered at a time t(*) approximately 4 ps,
      which corresponds to the intermediate region of <r(2)(t)> between microscopic
      dynamics and sublinear diffusion. The analysis of F(s)(Q,t), F(Q,t)/F(Q,0), and
      M2(t) focuses on the second slow step which is associated to the alpha
      relaxation. Following the usual experimental procedure this decay is described in
      terms of a Kohlrausch-Williams-Watts (KWW) function: A exp[-(t/tau)(beta)]. In
      the Q range below Q(max), where Q(max) is the value at which the static structure
      factor shows its first maximum, the Q dependence of the KWW relaxation time of
      F(s)(Q,t) follows a law tau approximately Q(-2/beta). This kind of Q dependence
      corresponds to a Gaussian behavior of G(s)(r,t) and F(s)(Q,t). This law has been
      experimentally found in this Q range for different polymers. In the higher Q
      range-not easily accessible experimentally-strong deviations from the Gaussian
      behavior manifest. This crossover from Gaussian to non-Gaussian behavior can be
      understood in the framework of the mode coupling theory as well as in terms of a
      crossover from homogeneous to heterogeneous dynamics. This last interpretation
      opens a possible way of rationalizing the apparent contradiction between the
      neutron scattering and relaxation techniques results concerning dynamical
      heterogeneity of the alpha relaxation.

PMID- 12005864
TI  - Conformation of a polyelectrolyte complexed to a like-charged colloid.
AB  - We report results from a molecular dynamics simulation on the conformations of a
      long flexible polyelectrolyte complexed to a charged sphere, both negatively
      charged, in the presence of neutralizing counterions in the strong Coulomb
      coupling regime. The structure of this complex is very sensitive to the charge
      density of the polyelectrolyte. For a fully charged polyelectrolyte the polymer
      forms a dense two-dimensional "disk," whereas for a partially charged
      polyelectrolyte the monomers are spread over the colloidal surface. A mechanism
      involving the overcharging of the polyelectrolyte by counterions is proposed to
      explain the observed conformations.

PMID- 12005865
TI  - Efficient computation of the structural phase behavior of block copolymers.
AB  - A numerical implementation of self-consistent mean-field theory for the
      structural phase behavior of block copolymers is proposed. Our scheme does not
      require a priori assumptions of the underlying mesoscopic symmetries. The method
      potentially enables us to characterize, with high accuracy, the structural phase
      diagram of block copolymers with significant architectural complexity. We
      illustrate the method by applying it to a triblock copolymer system.

PMID- 12005866
TI  - Computer simulation study on the swelling of a model polymer network by a
      chainlike solvent.
AB  - A molecular-dynamics-particle-transfer method was used to study the swelling of a
      model polymer network by a short chain solvent. The solvent chains were
      transferred depending on the difference between the solvent chemical potentials
      in the coupled simulation boxes, containing pure solvent and gel, respectively.
      The chemical potentials were computed via the Rosenbluth sampling method. The
      simulated swelling ratio of the network under subcritical and supercritical
      conditions is compared with the prediction of a modified Flory-Huggins theory. In
      addition, the chains exhibit markedly different structural and dynamic properties
      in the corresponding phases due to the constraint imposed by the network, which
      are discussed in detail.

PMID- 12005867
TI  - Fluid-membrane tethers: minimal surfaces and elastic boundary layers.
AB  - Thin cylindrical tethers are common lipid bilayer membrane structures, arising in
      situations ranging from micromanipulation experiments on artificial vesicles to
      the dynamic structure of the Golgi apparatus. We study the shape and formation of
      a tether in terms of the classical soap-film problem, which is applied to the
      case of a membrane disk under tension subject to a point force. A tether forms
      from the elastic boundary layer near the point of application of the force, for
      sufficiently large displacement. Analytic results for various aspects of the
      membrane shape are given.

PMID- 12005868
TI  - Dynamical properties of discrete breathers in curved chains with first and second
      neighbor interactions.
AB  - We present the study of discrete breather dynamics in curved polymerlike chains
      consisting of masses connected via nonlinear springs. The polymer chains are one
      dimensional but not rectilinear and their motion takes place on a plane. After
      constructing breathers following numerically accurate procedures, we launch them
      in the chains and investigate properties of their propagation dynamics. We find
      that breather motion is strongly affected by the presence of curved regions of
      polymers, while the breathers themselves show a very strong resilience and
      remarkable stability in the presence of geometrical changes. For chains with
      strong angular rigidity we find that breathers either pass through bent regions
      or get reflected while retaining their frequency. Their motion is practically
      lossless and seems to be determined through local energy conservation. For less
      rigid chains modeled via second neighbor interactions, we find similarly that
      chain geometry typically does not destroy the localized breather states but,
      contrary to the angularly rigid chains, it induces some small but constant energy
      loss. Furthermore, we find that a curved segment acts as an active gate
      reflecting or refracting the incident breather and transforming its velocity to a
      value that depends on the discrete breathers frequency. We analyze the physical
      reasoning behind these seemingly general breather properties.

PMID- 12005869
TI  - Performance of different synchronization measures in real data: a case study on
      electroencephalographic signals.
AB  - We study the synchronization between left and right hemisphere rat
      electroencephalographic (EEG) channels by using various synchronization measures,
      namely nonlinear interdependences, phase synchronizations, mutual information,
      cross correlation, and the coherence function. In passing we show a close
      relation between two recently proposed phase synchronization measures and we
      extend the definition of one of them. In three typical examples we observe that
      except mutual information, all these measures give a useful quantification that
      is hard to be guessed beforehand from the raw data. Despite their differences,
      results are qualitatively the same. Therefore, we claim that the applied measures
      are valuable for the study of synchronization in real data. Moreover, in the
      particular case of EEG signals their use as complementary variables could be of
      clinical relevance.

PMID- 12005870
TI  - Statistical properties of contact vectors.
AB  - We study the statistical properties of contact vectors, a construct to
      characterize a protein's structure. The contact vector of an N-residue protein is
      a list of N integers n(i), representing the number of residues in contact with
      residue i. We study analytically (at mean-field level) and numerically the amount
      of structural information contained in a contact vector. Analytical calculations
      reveal that a large variance in the contact numbers reduces the degeneracy of the
      mapping between contact vectors and structures. Exact enumeration for lengths up
      to N=16 on the three-dimensional cubic lattice indicates that the growth rate of
      number of contact vectors as a function of N is only 3% less than that for
      contact maps. In particular, for compact structures we present numerical evidence
      that, practically, each contact vector corresponds to only a handful of
      structures. We discuss how this information can be used for better structure
      prediction.

PMID- 12005871
TI  - Analysis of symbolic sequences using the Jensen-Shannon divergence.
AB  - We study statistical properties of the Jensen-Shannon divergence D, which
      quantifies the difference between probability distributions, and which has been
      widely applied to analyses of symbolic sequences. We present three
      interpretations of D in the framework of statistical physics, information theory,
      and mathematical statistics, and obtain approximations of the mean, the variance,
      and the probability distribution of D in random, uncorrelated sequences. We
      present a segmentation method based on D that is able to segment a nonstationary
      symbolic sequence into stationary subsequences, and apply this method to DNA
      sequences, which are known to be nonstationary on a wide range of different
      length scales.

PMID- 12005872
TI  - Plasticity and learning in a network of coupled phase oscillators.
AB  - A generalized Kuramoto model of coupled phase oscillators with a slow varying
      coupling matrix is studied. The dynamics of the coupling coefficients is driven
      by the phase difference of pairs of oscillators in such a way that the coupling
      strengthens for synchronized oscillators and weakens for nonsynchronized pairs.
      The system possesses a family of stable solutions corresponding to synchronized
      clusters of different sizes. A particular cluster can be formed by applying
      external driving at a given frequency to a group of oscillators. Once
      established, the synchronized state is robust against noise and small variations
      in natural frequencies. The phase differences between oscillators within the
      synchronized cluster can be used for information storage and retrieval.

PMID- 12005873
TI  - Force and kinetic barriers to initiation of DNA unzipping.
AB  - A semimicroscopic model of the binding of the two nucleotide strands in a double
      stranded DNA is used to describe the effects of applied tension on strand
      unpairing. We show that the model describes strand separation by elevated
      temperature, applied torque, and applied force. In particular, we show how the
      interactions responsible for stabilizing the double helix against thermal
      denaturation determine the approximately 12 pN force threshold for DNA strand
      separation. The larger rigidity of the strands when formed into double-stranded
      DNA, relative to that of isolated strands, gives rise to a potential barrier to
      unzipping. We show that this barrier results in a approximately 250 pN force
      barrier opposing the beginning of strand separation. The thermal-fluctuation
      assisted "tunnelling" through the barrier is then analyzed using instanton
      calculations. The resulting kinetics of unzipping initiation is shown to be
      consistent with solution-phase strand dissociation experiments, and can explain
      results of two recent unzipping experiments done using atomic-force microscopy.

PMID- 12005874
TI  - Dynamics of rumor propagation on small-world networks.
AB  - We study the dynamics of an epidemiclike model for the spread of a rumor on a
      small-world network. It has been shown that this model exhibits a transition
      between regimes of localization and propagation at a finite value of the network
      randomness. Here, by numerical means, we perform a quantitative characterization
      of the evolution in the two regimes. The variant of dynamic small worlds, where
      the quenched disorder of small-world networks is replaced by randomly changing
      connections between individuals, is also analyzed in detail and compared with a
      mean-field approximation.

PMID- 12005875
TI  - Identification of coupling direction: application to cardiorespiratory
      interaction.
AB  - We consider the problem of experimental detection of directionality of weak
      coupling between two self-sustained oscillators from bivariate data. We further
      develop the method introduced by Rosenblum and Pikovsky [Phys. Rev. E 64, 045202
      (2001)], suggesting an alternative approach. Next, we consider another framework
      for identification of directionality, based on the idea of mutual predictability.
      Our algorithms provide directionality index that shows whether the coupling
      between the oscillators is unidirectional or bidirectional, and quantifies the
      asymmetry of bidirectional coupling. We demonstrate the efficiency of three
      different algorithms in determination of directionality index from short and
      noisy data. These techniques are then applied to analysis of cardiorespiratory
      interaction in healthy infants. The results reveal that the direction of coupling
      between cardiovascular and respiratory systems varies with the age within the
      first 6 months of life. We find a tendency to change from nearly symmetric
      bidirectional interaction to nearly unidirectional one (from respiration to the
      cardiovascular system).

PMID- 12005876
TI  - Atomic force microscopy of height fluctuations of fibroblast cells.
AB  - We investigated the nanometer scale height fluctuations of 3T3 fibroblast cells
      with the atomic force microscope under physiological conditions. A correlation
      between these fluctuations and lateral cellular motility can be observed.
      Fluctuations measured on leading edges appear to be predominantly related to
      actin polymerization-depolymerization processes. We found fast (5 Hz) pulsatory
      behavior with 1-2 nm amplitude on a cell with low motility showing emphasized
      structure of stress fibers. Myosin driven contractions of stress fibers are
      thought to induce this pulsation.

PMID- 12005877
TI  - Grouping of residues based on their contact interactions.
AB  - Based on the concept of energy landscape a grouping method of residues for
      reducing the sequence complexity in proteins is presented. For the Miyazawa and
      Jernigan matrix, rational groupings of 20 kinds of residues with minimal
      mismatches, under the consideration of local minima and statistics on correlation
      between the residues, are studied. A hierarchical tree of groupings relating to
      different numbers of groups N is obtained, and a plateau around N=8-10 is found,
      which may represent the basic degree of freedom of the sequence complexity in
      proteins.

PMID- 12005878
TI  - Analytical characterization of adhering vesicles.
AB  - We characterize vesicle adhesion onto homogeneous substrates by means of a
      perturbative expansion around the infinite adhesion limit, where curvature
      elasticity effects are absent. At first order in curvature elasticity, we
      determine analytically various global physical quantities associated with
      adhering vesicles: height, adhesion radius, etc. Our results are valid for
      adhesion energies above a certain threshold, that we determine numerically. We
      discuss the haptotactic force acting on a vesicle in the limit of weak adhesion
      gradients. We also propose a few methods for measuring adhesion energies and we
      suggest a possible way of determining the size of suboptical vesicles using
      controlled adhesion gradients.

PMID- 12005879
TI  - Precision and reliability of periodically and quasiperiodically driven integrate
      and-fire neurons.
AB  - Neurons in the brain communicate via trains of all-or-none electric events known
      as spikes. How the brain encodes information using spikes-the neural code-remains
      elusive. Here the robustness against noise of stimulus-induced neural spike
      trains is studied in terms of attractors and bifurcations. The dynamics of model
      neurons converges after a transient onto an attractor yielding a reproducible
      sequence of spike times. At a bifurcation point the spike times on the attractor
      change discontinuously when a parameter is varied. Reliability, the stability of
      the attractor against noise, is reduced when the neuron operates close to a
      bifurcation point. We determined using analytical spike-time maps the attractor
      and bifurcation structure of an integrate-and-fire model neuron driven by a
      periodic or a quasiperiodic piecewise constant current and investigated the
      stability of attractors against noise. The integrate-and-fire model neuron became
      mode locked to the periodic current with a rational winding number p/q and
      produced p spikes per q cycles. There were q attractors. p:q mode-locking regions
      formed Arnold tongues. In the model, reliability was the highest during 1:1 mode
      locking when there was only one attractor, as was also observed in recent
      experiments. The quasiperiodically driven neuron mode locked to either one of the
      two drive periods, or to a linear combination of both of them. Mode-locking
      regions were organized in Arnold tongues and reliability was again highest when
      there was only one attractor. These results show that neuronal reliability in
      response to the rhythmic drive generated by synchronized networks of neurons is
      profoundly influenced by the location of the Arnold tongues in parameter space.

PMID- 12005880
TI  - Morphological ordering in biopolymers: informational statistical thermodynamic
      approach.
AB  - We consider the question of the emergence of morphological ordering in an open
      far-from-equilibrium model of a biopolymer. We apply informational statistical
      thermodynamics, which was shown to be appropriate to deal with dissipative
      systems displaying complex behavior. The formation of nonlinear spatial ordering
      consisting in the emergence of static charge-density waves, producing a
      bioelectret-type state, is evidenced. This kind of behavior may arise in
      biopolymers under the influence of biochemical processes.

PMID- 12005881
TI  - Noise-induced resonances in the Hindmarsh-Rose neuronal model.
AB  - The behavior of neurons under stimulation is often described by means of
      dynamical systems having bifurcations from fixed points to limit cycles. In these
      models, the presence of noise can induce irregular crossings of the bifurcation
      threshold leading to intrinsic oscillations of the system variables that describe
      the detection of the otherwise subthreshold signals by the neuron. In this paper,
      the response of the Hindmarsh-Rose neuronal model to noisy signals is
      investigated and a variety of noise-induced resonances are described.

PMID- 12005882
TI  - Coupling parameter in synchronization of diluted neural networks.
AB  - We study the critical features of a coupling parameter in the synchronization of
      neural networks with diluted synapses. Based on simulations, an exponential decay
      form is observed in the extreme case of global coupling among subsystems and full
      connection in each network: there exists a maximum and a minimum of the critical
      coupling intensity for synchronization in this spatially extended system. For
      partial coupling, we present the primary result about the critical coupling
      fraction for various linking degrees of the networks.

PMID- 12005883
TI  - Measurements of brain activity complexity for varying mental loads.
AB  - Using functional magnetic resonance imaging, we investigate the variation in
      dynamical complexity of human brain activity for different mental loads. Our
      experiments measured the activity of ten subjects under three experimental
      conditions: a rest condition, a periodic task of finger opposition, and a task of
      finger opposition alternated with mathematical serial calculation. We used the
      correlation dimension to gauge the spatiotemporal complexity of brain activity.
      The experiments show a direct relationship between this complexity and the
      difficulty of the task. A natural interpretation is that higher levels of mental
      load recruit a larger number of independent neural processes that contribute to
      complex brain dynamics. These results suggest the possibility that the relative
      change in correlation dimension can be a useful global measure of brain dynamics,
      e.g., in determining the levels of mental activity, even if little is known about
      the underlying neurological processes.

PMID- 12005884
TI  - Replica symmetric evaluation of the information transfer in a two-layer network
      in the presence of continuous and discrete stimuli.
AB  - In a previous paper we have evaluated analytically the mutual information between
      the firing rates of N independent units and a set of multidimensional continuous
      and discrete stimuli, for a finite population size and in the limit of large
      noise. Here, we extend the analysis to the case of two interconnected
      populations, where input units activate output ones via Gaussian weights and a
      threshold linear transfer function. We evaluate the information carried by a
      population of M output units, again about continuous and discrete correlates. The
      mutual information is evaluated solving saddle-point equations under the
      assumption of replica symmetry, a method that, by taking into account only the
      term linear in N of the input information, is equivalent to assuming the noise to
      be large. Within this limitation, we analyze the dependence of the information on
      the ratio M/N, on the selectivity of the input units and on the level of the
      output noise. We show analytically, and confirm numerically, that in the limit of
      a linear transfer function and of a small ratio between output and input noise,
      the output information approaches asymptotically the information carried in
      input. Finally, we show that the information loss in output does not depend much
      on the structure of the stimulus, whether purely continuous, purely discrete or
      mixed, but only on the position of the threshold nonlinearity, and on the ratio
      between input and output noise.

PMID- 12005885
TI  - Zero-temperature properties of RNA secondary structures.
AB  - We analyze different microscopic RNA models at zero temperature. We discuss both
      the most simple model, which suffers a large degeneracy of the ground state, and
      models in which the degeneracy has been removed in a more or less severe manner.
      We calculate low-energy density of states using a coupling perturbing method,
      where the ground state of a modified Hamiltonian, that repels the original ground
      state, is determined. We evaluate scaling exponents starting from measurements of
      overlaps and energy differences. In the case of models without accidental
      degeneracy of the ground state we are able to clearly establish the existence of
      a glassy phase with theta approximately 1/3. 87.15.Aa, 64.60.Fr

PMID- 12005886
TI  - Improved energy model for membrane electroporation in biological cells subjected
      to electrical pulses.
AB  - A self-consistent model analysis of electroporation in biological cells has been
      carried out based on an improved energy model. The simple energy model used in
      the literature is somewhat incorrect and unphysical for a variety of reasons. Our
      model for the pore formation energy E(r) includes a dependence on pore population
      and density. It also allows for variable surface tension, incorporates the
      effects of finite conductivity on the electrostatic correction term, and is
      dynamic in nature. Self-consistent calculations, based on a coupled scheme
      involving the Smoluchowski equation and the improved energy model, are presented.
      It is shown that E(r) becomes self-adjusting with variations in its magnitude and
      profile, in response to pore population, and inhibits uncontrolled pore growth
      and expansion. This theory can be augmented to include pore-pore interactions to
      move beyond the independent pore picture.

PMID- 12005887
TI  - Dynamic light scattering from an optically trapped microsphere.
AB  - Using a single microscope objective lens to optically trap, illuminate, and
      collect backscattered light of a dielectric microsphere, we measure the temporal
      intensity-autocorrelation functions (ACFs), and intensity profiles to obtain the
      trap stiffness and friction coefficient of the bead. This is an interesting study
      of an harmonically bound Brownian particle, with nanometer resolution. We extend
      the work of Bar-Ziv et al. [Phys. Rev. Lett. 78, 154 (1997)] to more general
      situations allowing for the use of our simpler geometry in other applications. As
      examples, we present measurements of the parallel Stokes friction coefficient on
      the trapped bead as a function of its distance from a surface and the entropic
      force of a single lambda-DNA molecule.

PMID- 12005888
TI  - Modeling of spiking-bursting neural behavior using two-dimensional map.
AB  - A simple model that replicates the dynamics of spiking and spiking-bursting
      activity of real biological neurons is proposed. The model is a two-dimensional
      map that contains one fast and one slow variable. The mechanisms behind
      generation of spikes, bursts of spikes, and restructuring of the map behavior are
      explained using phase portrait analysis. The dynamics of two coupled maps that
      model the behavior of two electrically coupled neurons is discussed.
      Synchronization regimes for spiking and bursting activities of these maps are
      studied as a function of coupling strength. It is demonstrated that the results
      of this model are in agreement with the synchronization of chaotic spiking
      bursting behavior experimentally found in real biological neurons.

PMID- 12005889
TI  - Geometric and statistical properties of the mean-field hydrophobic-polar model,
      the large-small model, and real protein sequences.
AB  - Lattice models, for their coarse-grained nature, are best suited for the study of
      the "designability problem," the phenomenon in which most of the about 16 000
      proteins of known structure have their native conformations concentrated in a
      relatively small number of about 500 topological classes of conformations. Here
      it is shown that on a lattice the most highly designable simulated protein
      structures are those that have the largest number of surface-core switchbacks. A
      combination of physical, mathematical, and biological reasons that causes the
      phenomenon is given. By comparing the most foldable model peptides with protein
      sequences in the Protein Data Bank, it is shown that whereas different models may
      yield similar designabilities, predicted foldable peptides will simulate natural
      proteins only when the model incorporates the correct physics and biology, in
      this case if the main folding force arises from the differing hydrophobicity of
      the residues, but does not originate, say, from the steric hindrance effect
      caused by the differing sizes of the residues.

PMID- 12005890
TI  - Dynamics of large-scale brain activity in normal arousal states and epileptic
      seizures.
AB  - Links between electroencephalograms (EEGs) and underlying aspects of
      neurophysiology and anatomy are poorly understood. Here a nonlinear continuum
      model of large-scale brain electrical activity is used to analyze arousal states
      and their stability and nonlinear dynamics for physiologically realistic
      parameters. A simple ordered arousal sequence in a reduced parameter space is
      inferred and found to be consistent with experimentally determined parameters of
      waking states. Instabilities arise at spectral peaks of the major clinically
      observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle
      with each instability zone lying near its most common experimental precursor
      arousal states in the reduced space. Theta, alpha, and spindle instabilities
      evolve toward low-dimensional nonlinear limit cycles that correspond closely to
      EEGs of petit mal seizures for theta instability, and grand mal seizures for the
      other types. Nonlinear stimulus-induced entrainment and seizures are also seen,
      EEG spectra and potentials evoked by stimuli are reproduced, and numerous other
      points of experimental agreement are found. Inverse modeling enables
      physiological parameters underlying observed EEGs to be determined by a new,
      noninvasive route. This model thus provides a single, powerful framework for
      quantitative understanding of a wide variety of brain phenomena.

PMID- 12005891
TI  - Kinetic transition in model proteins with a denatured native spinodal.
AB  - The relaxation kinetics of three-dimensional lattice model proteins with Go
      potential is studied. A kinetic transition from an exponential behavior to a
      nonexponential one with a denatured native spinodal is characterized. The
      transition temperatures T(k), obtained from simulations and a semiquantitative
      estimation, are found to be the same. The change in free energy landscape during
      the transition is discussed microscopically by studying the detailed folding
      processes of various paths. The connection of T(k) with the foldability is also
      studied by a Z-score-like quantity T(f)/T(k).

PMID- 12005892
TI  - Memory beyond memory in heart beating, a sign of a healthy physiological
      condition.
AB  - We describe two types of memory and illustrate each using artificial and actual
      heartbeat data sets. The first type of memory, yielding anomalous diffusion,
      implies the inverse power-law nature of the waiting time distribution and the
      second the correlation among distinct times, and consequently also the occurrence
      of many pseudoevents, namely, not genuinely random events. Using the method of
      diffusion entropy analysis, we establish the scaling that would be determined by
      the real events alone. We prove that the heart beating of healthy patients
      reveals the existence of many more pseudoevents than in the patients with
      congestive heart failure.

PMID- 12005893
TI  - Separation quality of a geometric ratchet.
AB  - We consider an experimentally relevant model of a geometric ratchet in which
      particles undergo drift and diffusive motion in a two-dimensional periodic array
      of obstacles, and which is used for the continuous separation of particles
      subject to different forces. The macroscopic drift velocity and diffusion tensor
      are calculated by a Monte Carlo simulation and by a master-equation approach,
      using the corresponding microscopic quantities and the shape of the obstacles as
      input. We define a measure of separation quality and investigate its dependence
      on the applied force and the shape of the obstacles.

PMID- 12005894
TI  - Finding transition paths and rate coefficients through accelerated Langevin
      dynamics.
AB  - We present a technique to resolve the rare event problem for a Langevin equation
      describing a system with thermally activated transitions. A transition event
      within a given time interval (0,t(f)) can be described by a transition path that
      has an activation part during (0,t(M)) and a deactivation part during
      (t(M),t(f))(0<t(M)<t(f)). The activation path is governed by a Langevin equation
      with negative friction while the deactivation path by the standard Langevin
      equation with positive friction. Each transition path carries a given statistical
      weight from which rate constants and related physical quantities can be obtained
      as averages over all possible paths. We demonstrate how this technique can be
      used to calculate activation rates of a particle in a two dimensional potential
      for a wide range of temperatures where standard molecular dynamics techniques are
      inefficient.

PMID- 12005895
TI  - Adhesion between weakly rough beads.
AB  - Cohesion effects are of prime importance in powders and granular media, and they
      are strongly affected by the roughness of the grain surface. We report
      measurements of the adhesion force between surfaces of Pyrex having a nanometric
      roughness, with a surface force apparatus. The two surfaces are immersed in
      liquid n-dodecane. The adhesion force measured is much smaller than expected in
      the case of smooth surfaces. We find that the adhesion force depends on the
      maximal load that has been applied on the surfaces, but does not depend on the
      time during which they have been in contact. We propose a model of plastic
      deformation of the small asperities in a macroscopic Hertz contact which is in
      good agreement with the experimental data.

PMID- 12005896
TI  - Critical behavior in broad-band dielectric relaxation on approaching the critical
      consolute point in ethanol-dodecane mixture.
AB  - We present a quantitative experimental evidence for the influence of critical
      fluctuations on the high frequency dielectric relaxation in a binary critical
      mixture. The analysis clearly shows the presence of critical anomaly both for the
      maxima (epsilon(")(p)) and frequencies (f(p)) of loss curves peaks. For the
      temperature evolution of epsilon(")(p) similar relation as for the static
      dielectric permittivity was obtained. The temperature dependence of relaxation
      times can be portrayed by using the Eyring-type equation remote from the critical
      consolute point and shows the unusual precritical speeding up. The obtained
      behavior resembles that found recently in the isotropic phase of nematic liquid
      crystals [A. Drozd-Rzoska and S. J. Rzoska, Phys. Rev. E 65, 041701 (2002)].
      Results presented agree also with the recent theoretical suggestion [S. Goodyear
      and S. C. Tucker, J. Chem. Phys. 111, 9673 (1999)] that relaxation in
      supercritical fluids may exhibit glasslike features.

PMID- 12005897
TI  - Cluster persistence of two-dimensional soap froth.
AB  - We report on the persistence decay of cell clusters in dynamical simulation of
      two-dimensional soap-froth as a function of the cluster volume fraction. Both
      slow gas diffusion and fast dynamical topological processes between cells are
      incorporated in the simulation. While the simulation yields decay rate in good
      agreement with two-dimensional soap-froth experiment, it shows a faster decay in
      comparison to measurements and calculations of persistence in other curvature
      driven systems. The fraction of individual cells that contain persistent area
      also decays due to significant cell movements, confirming that the neighbor
      swapping T1 topological transition is important in froth coarsening.

PMID- 12005898
TI  - Two-dimensional copolymers and multifractality: comparing perturbative
      expansions, Monte Carlo simulations, and exact results.
AB  - We analyze the scaling laws for a set of two different species of long flexible
      polymer chains joined together at one of their extremities (copolymer stars) in
      space dimension D=2. We use a formerly constructed field-theoretic description
      and compare our perturbative results for the scaling exponents with recent
      conjectures for exact conformal scaling dimensions derived by a conformal
      invariance technique in the context of D=2 quantum gravity. A simple Monte Carlo
      simulation brings about reasonable agreement with both approaches. We analyze the
      remarkable multifractal properties of the spectrum of scaling exponents.

PMID- 12005899
TI  - Nonequilibrium pattern formation in the crystallization of polymer blend films.
AB  - We show that the morphology of polyethylene oxide crystallization in thin films
      can be tuned to obtain circular spherulites, seaweed and symmetric dendrites, and
      fractal aggregation forms through the addition of clay particles and the
      amorphous polymer, polymethyl methacrylate. The thin-film polymer crystallization
      patterns are compared to a two-dimensional phase field model of dendritic growth
      in Ni/Cu alloys with a variable surface tension anisotropy epsilon. Some aspects
      of polymer crystallization patterns can be understood from the phase field
      calculations, but a more general model is required to describe the full range of
      observed patterns.

PMID- 12005900
TI  - Analysis of diffusion in a solid polymer electrolyte in the context of a phase
      separated system.
AB  - The salt and ionic diffusion coefficients of the salt LiN(CF3SO2)(2) (LiTFSI)
      dissolved in high-molecular-weight poly(ethylene oxide) [PEO] have been measured
      over a broad concentration range, and the interrelationship of the measured
      values is demonstrated to be in good agreement with basic electrochemical theory.
      In the light of recently published structural findings, we propose a biphasic
      model for the conducting amorphous state, consisting of a stoichiometric
      P(EO)6LiTFSI phase dispersed into a salt-containing disordered phase, and analyze
      the ionic diffusion data within the framework of the Bruggeman-Landauer theory.
      The agreement between experimental and fitted data is shown to be excellent. We
      conclude by pointing out and discussing potential weaknesses of our analysis.

PMID- 12005901
TI  - Quasistatic fractures in brittle media and iterated conformal maps.
AB  - We study the geometrical characteristic of quasistatic fractures in brittle
      media, using iterated conformal maps to determine the evolution of the fracture
      pattern. This method allows an efficient and accurate solution of the Lame
      equations without resorting to lattice models. Typical fracture patterns exhibit
      increased ramification due to the increase of the stress at the tips. We find the
      roughness exponent of the experimentally relevant backbone of the fracture
      pattern, it crosses over from about 0.5 for small scales to about 0.75 for large
      scales. We propose that this crossover reflects the increased ramification of the
      fracture pattern.

PMID- 12005902
TI  - Functional form of the Parisi overlap distribution for the three-dimensional
      Edwards-Anderson Ising spin glass.
AB  - Recently, it has been conjectured that the statistics of extremes is of relevance
      for a large class of correlated systems. For certain probability densities this
      predicts the characteristic large x falloff behavior f(x) approximately exp(
      ae(x)), a>0. Using a multicanonical Monte Carlo technique, we have measured the
      Parisi overlap distribution P(q) for the three-dimensional Edward-Anderson Ising
      spin glass at and below the critical temperature We find that a probability
      distribution related to extreme-order statistics gives an excellent description
      of P(q) over about 80 orders of magnitude.

PMID- 12005903
TI  - Jamming coverage in competitive random sequential adsorption of a binary mixture.
AB  - We propose a generalized car parking problem where cars of two different sizes
      are sequentially parked on a line with a given probability q. The free parameter
      q interpolates between the classical car parking problem of only one car size and
      the competitive random sequential adsorption (CRSA) of a binary mixture. We give
      an exact solution to the CRSA rate equations and find that the final coverage,
      the jamming limit of the line, is always larger for a binary mixture than for the
      unisized case. The analytical results are in good agreement with our direct
      numerical simulations of the problem.

PMID- 12005904
TI  - Multifractal current distribution in random-diode networks.
AB  - Recently it has been shown analytically that electric currents in a random-diode
      network are distributed in a multifractal manner [O. Stenull and H. K. Janssen,
      Europhys. Lett. 55, 691 (2001)]. In the present paper we investigate the
      multifractal properties of a random diode network at the critical point by
      numerical simulations. We analyze the currents running on a directed percolation
      cluster and confirm the field-theoretic predictions for the scaling behavior of
      moments of the current distribution. It is pointed out that a random diode
      network is a particularly good candidate for a possible experimental realization
      of directed percolation.

PMID- 12005905
TI  - Coupled map networks as communication schemes.
AB  - Networks of chaotic coupled maps are considered as string and language
      generators. It is shown that such networks can be used as encrypting systems
      where the cipher text contains information about the evolution of the network and
      also about the way to select the plain text symbols from the string associated
      with the network evolution. The secret key provides the network parameters, such
      as the coupling strengths.

PMID- 12005906
TI  - Rhythmic bursting in a cluster of microbeads driven by a continuous-wave laser
      beam.
AB  - Rhythmic bursting on the order of seconds in a cluster of plastic beads under
      continuous irradiation of a focused neodymium-doped yttrium aluminum garnet
      (Nd:YAG) laser beam (1064 nm) is reported. The oscillatory instability is induced
      as a result of competition between trapping and scattering forces, where both
      forces are induced by the focused laser beam. Above a critical power of the laser
      beam, mode bifurcation from the stationary state into periodic bursting is
      observed. Our model employing ordinary differential equations reproduces the
      essential aspects of the experimental results.

PMID- 12005907
TI  - Bailout embeddings, targeting of invariant tori, and the control of Hamiltonian
      chaos.
AB  - We introduce a technique, which we term bailout embedding, that can be used to
      target orbits having particular properties out of all orbits in a flow or map. We
      explicitly construct a bailout embedding for Hamiltonian systems so as to target
      invariant tori. We show how the bailout dynamics are able to lock onto extremely
      small regular islands in a chaotic sea.

PMID- 12005908
TI  - Information transfer and nontrivial collective behavior in chaotic coupled map
      networks.
AB  - The emergence of nontrivial collective behavior in networks of coupled chaotic
      maps is investigated by means of a nonlinear mutual prediction method. The
      resulting prediction error is used to measure the amount of information that a
      local unit possesses about the collective dynamics. Applications to locally and
      globally coupled map systems are considered. The prediction error exhibits phase
      transitions at critical values of the coupling for the onset of ordered
      collective behavior in these networks. This information measure may be used as an
      order parameter for the characterization of complex behavior in extended chaotic
      systems.

PMID- 12005909
TI  - Non-Hermiticity in a kicked model: decoherence and the semiclassical limit.
AB  - We study the effects of non-Hermitian perturbations on a quantum kicked model
      exhibiting a localization transition. Using an exact renormalization scheme, we
      show that the critical line separating the extended and localized phases
      approaches its semiclassical limit as the imaginary part of the kicking parameter
      is steadily increased. Further, the metastability of the quantum states appears
      to be directly correlated with the deviation between the semiclassical and
      quantum results. This direct evidence of quantum-classical correspondence
      suggests that decoherence may be usefully modeled by non-Hermitian perturbations.

PMID- 12005910
TI  - Decoherence as decay of the Loschmidt echo in a Lorentz gas.
AB  - Classical chaotic dynamics is characterized by exponential sensitivity to initial
      conditions. Quantum mechanics, however, does not show this feature. We consider
      instead the sensitivity of quantum evolution to perturbations in the Hamiltonian.
      This is observed as an attenuation of the Loschmidt echo M(t), i.e., the amount
      of the original state (wave packet of width sigma) which is recovered after a
      time reversed evolution, in the presence of a classically weak perturbation. By
      considering a Lorentz gas of size L, which for large L is a model for an
      unbounded classically chaotic system, we find numerical evidence that, if the
      perturbation is within a certain range, M(t) decays exponentially with a rate
      1/tau(phi) determined by the Lyapunov exponent lambda of the corresponding
      classical dynamics. This exponential decay extends much beyond the Eherenfest
      time t(E) and saturates at a time t(s) approximately equal to lambda(-1)ln[N],
      where N approximately (L/sigma)(2) is the effective dimensionality of the Hilbert
      space. Since tau(phi) quantifies the increasing uncontrollability of the quantum
      phase (decoherence) its characterization and control has fundamental interest.

PMID- 12005911
TI  - Global quantitative predictions of complex laser dynamics.
AB  - We demonstrate unprecedented agreement between a theoretical two-dimensional
      bifurcation diagram and the corresponding experimental stability map of an
      optically injected semiconductor laser over a large range of relevant injection
      parameter values. The bifurcation diagram encompasses both local and global
      bifurcations mapping out regions of regular, chaotic, and multistable behavior in
      considerable detail. This demonstrates the power of dynamical systems modeling
      for the quantitative prediction of nonlinear dynamics and chaos of semiconductor
      lasers.

PMID- 12005912
TI  - Flow of thin films on patterned surfaces: controlling the instability.
AB  - We present fully nonlinear time-dependent simulations of the gravity-driven flow
      of thin wetting liquid films. The computations of the flow on a homogeneous
      substrate show that the contact line, becomes unstable and develops a finger-like
      or sawtooth structure [Phys. Rev. Lett. 86, 632 (2001)]. These computations are
      extended to patterned surfaces, where surface heterogeneities are introduced in a
      controllable manner. We discuss the conditions that need to be satisfied so that
      surface properties lead to predictable pattern formation and controllable wetting
      of the substrate. These conditions are sensitive to the presence of noise which
      is introduced by random perturbations of the contact line. We analyze this
      sensitivity and suggest how the effects of noise can be minimized. Applications
      of these results to technologically relevant flows are discussed.

PMID- 12005913
TI  - Perturbation transfer from the front to rear surface of laser-irradiated targets.
AB  - We present experimental results on the perturbation transfer of laser irradiated
      planar foils. Perturbed polystyrene foils were irradiated directly by laser at
      intensity of 6 x 10(13) W/cm(2). We measured perturbations on the foils by side
      on x-ray backlighting technique. Perturbations on the rear surface due to the
      rippled shock front were observed just after the shock breakout. We also observed
      feed-through of perturbations on the laser-irradiated surface that grows due to
      the Rayleigh-Taylor instability.

PMID- 12005914
TI  - Polarization effects and anisotropy in three-dimensional relativistic self
      focusing.
AB  - The relativistic self-focusing of high-intensity laser pulses in underdense
      plasmas is investigated with three-dimensional particle in cell simulations. The
      different behavior of a linearly polarized pulse in the two transverse directions
      is interpreted as a combination of two two-dimensional responses with different
      polarizations. In the polarization plane a high density sheet is formed, which
      separates the two regions of oppositely directed quasistatic magnetic field.

PMID- 12005915
TI  - Dynamic Mach cone as a diagnostic method in reactive dusty plasma experiments.
AB  - We demonstrate how the observation of dynamic Mach cones in dusty plasma
      experiments allows one to follow the evolution of the dust acoustic wave velocity
      as charges on dust particles change, or as their mass changes. In experiments in
      which only the charge is changing due to, e.g., the application of a thin coating
      on UV-illuminated dust particles, the coating rate may be inferred through the
      analysis of the Mach cone pattern. In other experiments where the dust sizes are
      changing, also leading to some change in charge, the growth rate can be followed.

PMID- 12005916
TI  - Generalized emissivity inverse problem.
AB  - Inverse problems have recently drawn considerable attention from the physics
      community due to of potential widespread applications [K. Chadan and P. C.
      Sabatier, Inverse Problems in Quantum Scattering Theory, 2nd ed. (Springer
      Verlag, Berlin, 1989)]. An inverse emissivity problem that determines the
      emissivity g(nu) from measurements of only the total radiated power J(T) has
      recently been studied [Tao Wen, DengMing Ming, Xianxi Dai, Jixin Dai, and William
      E. Evenson, Phys. Rev. E 63, 045601(R) (2001)]. In this paper, a new type of
      generalized emissivity and transmissivity inverse (GETI) problem is proposed. The
      present problem differs from our previous work on inverse problems by allowing
      the unknown (emissivity) function g(nu) to be temperature dependent as well as
      frequency dependent. Based on published experimental information, we have
      developed an exact solution formula for this GETI problem. A universal function
      set suggested for numerical calculation is shown to be robust, making this
      inversion method practical and convenient for realistic calculations.

PMID- 12005917
TI  - Experimental observation of superluminal pulse reflection in a double-Lorentzian
      photonic band gap.
AB  - We report on the experimental observation of superluminal reflection of
      picosecond optical pulses at 1.5 microm using a specially designed 30-cm-long
      fiber Bragg grating (FBG) that realizes a spectral reflectivity profile given by
      the superposition of two closely spaced Lorentzian lines. Probing pulses of 380
      ps duration tuned midway between the two Lorentzian lines are reflected without
      appreciable distortion with a measured peak pulse advancement of approximately 60
      ps. The achievement of the negative group delay is due to the interference of the
      two resonance modes of the FBG structure and has a close connection to the
      phenomenon of negative group velocity for pulse propagation in an inverted medium
      possessing a doublet line.

PMID- 12005918
TI  - Fresnel laws at curved dielectric interfaces of microresonators.
AB  - We discuss curvature corrections to Fresnel's laws for the reflection and
      transmission of light at a nonplanar refractive-index boundary. The reflection
      coefficients are obtained from the resonances of a dielectric disk within a
      sequential-reflection model. The Goos-Hanchen effect for curved light fronts at a
      planar interface can be adapted to provide a qualitative and quantitative
      extension of the ray model which explains the observed deviations from Fresnel's
      laws.

PMID- 12005919
TI  - Amplitude coda of classical waves in disordered media.
AB  - The propagation of classical waves in the presence of a disordered medium is
      studied. We consider wave pulses containing a broad range of frequencies in terms
      of the configurationally averaged Green function of the system. Damped
      oscillations in the time-dependent response trailing behind the direct arrival of
      the pulse (coda) are predicted, the periods of which are governed by the density
      of scatterers.

PMID- 12005920
TI  - Probabilistic approach to the Bak-Sneppen model.
AB  - We study here the Bak-Sneppen model, a prototype model for the study of self
      organized criticality. In this model several species interact and undergo
      extinction with a power-law distribution of activity bursts. Species are defined
      through their "fitness" whose distribution in the system is uniform above a
      certain threshold. Run time statistics is introduced for the analysis of the
      dynamics in order to explain the peculiar properties of the model. This approach
      based on conditional probability theory, takes into account the correlations due
      to memory effects. In this way, we may compute analytically the value of the
      fitness threshold with the desired precision. This represents a substantial
      improvement with respect to the traditional mean field approach.

PMID- 12005921
TI  - Quantum decoherence, Zeno process, and time symmetry breaking.
AB  - The complex spectral representation of the Liouville-von Neumann operator outside
      Hilbert space is applied to the decoherence problem in quantum Brownian motion.
      In contrast to the path-integral method, often used in the context of quantum
      decoherence for the case where the environment surrounding the Brownian particle
      (subsystem) is in thermal equilibrium, our spectral representation is applicable
      to systems far from equilibrium, including a pure state for the surrounding bath.
      Starting with this pure initial condition, the subsystem evolves in time obeying
      a diffusion-type kinetic equation. Hence, the collapse of wave functions is a
      dynamical phenomenon occurring outside Hilbert space, and is not simply a
      contamination of the subsystem, a popular view accepted in the so-called
      "environmental" approach, by the mixed nature of the thermal bath. The essential
      element in the understanding of quantum decoherence is the "extensivity" of
      quantities characterizing the thermodynamic limit. Quantum Zeno time is shown to
      be a lower bound of the decoherence time.

PMID- 12005922
TI  - Highway on-ramp control.
AB  - We study the phase transition on a highway induced by the fluctuations of on-ramp
      flow. The highway traffic is provided by a hydrodynamical model. We analyze the
      characteristics of perturbations to induce congestion near on ramp. The phase
      boundary is obtained. A scaling relation is revealed. We also analyze the time
      evolution of the local density profile. Conventional control mechanisms to
      regulate the on-ramp flow are examined. A control scheme is proposed to suppress
      the congestion.

PMID- 12005923
TI  - Simple absorbing-state transition.
AB  - We study a simple reaction-diffusion process that exhibits a phase transition to
      an absorbing phase in its steady state. We characterize the universal properties
      of the transition by computing the associated critical exponents. We suggest that
      the exclusion constraint between particles may change the universality class of
      the transition even though the density is asymptotically low at the transition.
      This is surprising as no segregation or jamming phenomena are in play since we
      are dealing with a single species diffusing without drift.

PMID- 12005924
TI  - Trapped interacting Bose gas in nonextensive statistical mechanics.
AB  - We study the Bose-Einstein condensation (BEC) phenomenon in an interacting
      trapped Bose gas using the semiclassical two-fluid model and nonextensive
      statistical mechanics. The effects of nonextensivity characterized by a parameter
      are explored by calculating the temperature dependent thermodynamic properties,
      fraction of condensed particles, and density distributions of condensed and
      thermal components of the system. It is found that nonextensivity in the
      underlying statistical mechanics may have large effects on the BEC transition
      temperature.

PMID- 12005925
TI  - Ensemble-based control of evolutionary optimization algorithms.
AB  - This paper presents a study on how the intrinsic search parameters of an
      evolutionary optimization algorithm can be automatically controlled. It will be
      shown that only a small search parameter window ensures good optimization
      results. This evolutionary window, enclosing effective values for the mutation
      rate and temperature, can be adapted to by carefully steering the ensemble's
      fitness dispersion. A control sensor based on an entropy measure is introduced to
      achieve this goal. The efficiency of the proposed control method will be tested
      by optimizing artificial sequences such as the well-known low autocorrelated
      binary strings and natural sequences including RNA.

PMID- 12005926
TI  - Quantification of heart rate variability by discrete nonstationary non-Markov
      stochastic processes.
AB  - We develop the statistical theory of discrete nonstationary non-Markov random
      processes in complex systems. The objective of this paper is to find the chain of
      finite-difference non-Markov kinetic equations for time correlation functions
      (TCF) in terms of nonstationary effects. The developed theory starts from careful
      analysis of time correlation through nonstationary dynamics of vectors of initial
      and final states and nonstationary normalized TCF. Using the projection operators
      technique we find the chain of finite-difference non-Markov kinetic equations for
      discrete nonstationary TCF and for the set of nonstationary discrete memory
      functions (MF's). The last one contains supplementary information about
      nonstationary properties of the complex system on the whole. Another relevant
      result of our theory is the construction of the set of dynamic parameters of
      nonstationarity, which contains some information of the nonstationarity effects.
      The full set of dynamic, spectral and kinetic parameters, and kinetic functions
      (TCF, short MF's statistical spectra of non-Markovity parameter, and statistical
      spectra of nonstationarity parameter) has made it possible to acquire the in
      depth information about discreteness, non-Markov effects, long-range memory, and
      nonstationarity of the underlying processes. The developed theory is applied to
      analyze the long-time (Holter) series of RR intervals of human ECG's. We had two
      groups of patients: the healthy ones and the patients after myocardial
      infarction. In both groups we observed effects of fractality, standard and
      restricted self-organized criticality, and also a certain specific arrangement of
      spectral lines. The received results demonstrate that the power spectra of all
      orders (n=1,2, ...) MF m(n)(t) exhibit the neatly expressed fractal features. We
      have found out that the full sets of non-Markov, discrete and nonstationary
      parameters can serve as reliable and powerful means of diagnosis of the
      cardiovascular system states and can be used to distinguish healthy data from
      pathologic data.

PMID- 12005927
TI  - Monte Carlo simulation of the transmission of measles: beyond the mass action
      principle.
AB  - We present a Monte Carlo simulation of the transmission of measles within a
      population sample during its growing and equilibrium states by introducing two
      different vaccination schedules of one and two doses. We study the effects of the
      contact rate per unit time xi as well as the initial conditions on the
      persistence of the disease. We found a weak effect of the initial conditions
      while the disease persists when xi lies in the range 1/L-10/L (L being the latent
      period). Further comparison with existing data, prediction of future epidemics
      and other estimations of the vaccination efficiency are provided. Finally, we
      compare our approach to the models using the mass action principle in the first
      and another epidemic region and found the incidence independent of the number of
      susceptibles after the epidemic peak while it strongly fluctuates in its growing
      region. This method can be easily applied to other human, animal, and plant
      diseases and includes more complicated parameters.

PMID- 12005928
TI  - Multifractal structure of the harmonic measure of diffusion-limited aggregates.
AB  - The method of iterated conformal maps allows one to study the harmonic measure of
      diffusion-limited aggregates with unprecedented accuracy. We employ this method
      to explore the multifractal properties of the measure, including the scaling of
      the measure in the deepest fjords that were hitherto screened away from any
      numerical probing. We resolve probabilities as small as 10(-35), and present an
      accurate determination of the generalized dimensions and the spectrum of
      singularities. We show that the generalized dimensions D(q) are infinite for
      q<q*, where q* is of the order of -0.2. In the language of f(alpha) this means
      that alpha(max) is finite. The f(alpha) curve loses analyticity (the phenomenon
      of "phase transition") at alpha(max) and a finite value of f(alpha(max)). We
      consider the geometric structure of the regions that support the lowest parts of
      the harmonic measure, and thus offer an explanation for the phase transition,
      rationalizing the value of q* and f(alpha(max)). We thus offer a satisfactory
      physical picture of the scaling properties of this multifractal measure.

PMID- 12005929
TI  - Critical behavior of nonequilibrium phase transitions to magnetically ordered
      states.
AB  - We describe nonequilibrium phase transitions in arrays of dynamical systems with
      cubic nonlinearity driven by multiplicative Gaussian white noise. Depending on
      the sign of the spatial coupling we observe transitions to ferromagnetic or
      antiferromagnetic ordered states. We discuss the phase diagram, the order of the
      transitions, and the critical behavior. For global coupling we show analytically
      that the critical exponent of the magnetization exhibits a transition from the
      value 1/2 to a nonuniversal behavior depending on the ratio of noise strength to
      the magnitude of the spatial coupling.

PMID- 12005930
TI  - Finite-size scaling in the steady state of the fully asymmetric exclusion
      process.
AB  - Finite-size scaling expressions for the current near the continuous phase
      transition and for the local density near the first-order transition are found in
      the steady state of the one-dimensional fully asymmetric simple-exclusion process
      with open boundaries and discrete-time dynamics. The corresponding finite-size
      scaling variables are identified as the ratio of the chain length to the
      localization length of the relevant domain wall.

PMID- 12005931
TI  - Dynamical response of an excitatory-inhibitory neural network to external
      stimulation: an application to image segmentation.
AB  - Neural network models comprising elements that have exclusively excitatory or
      inhibitory synapses are capable of a wide range of dynamical behavior, including
      chaos. In this paper, a simple excitatory-inhibitory neural pair, which forms the
      building block of larger networks, is subjected to external stimulation. The
      response shows transition between various types of dynamics, depending upon the
      magnitude of the stimulus. The corresponding network model, obtained by coupling
      such pairs over a local neighborhood in a two-dimensional plane, can achieve a
      satisfactory segmentation of an image into "object" and "background." Results for
      synthetic and "real-life" images are given.

PMID- 12005932
TI  - Multiscale dynamics and robust critical scaling in a continuum current sheet
      model.
AB  - We analyze the self-organized critical behavior of a continuum running avalanche
      model. We demonstrate that over local interaction scales, the model behavior is
      affected by low-dimensional chaotic dynamics that plays the role of the primary
      noise source. With the help of scale-free avalanches, the uncertainty associated
      with chaos is distributed over a variety of intermediate scales and thus gives
      rise to spatiotemporal fluctuations that are characterized by power-law
      distribution functions. We show that globally, the continuum model displays
      structurally stable critical scaling that can be observed in a finite region in
      the control parameter space. In this region, the system exhibits a power-law
      critical divergence of the integrated response function over a broad range of
      dissipation rates. The observed behavior involves a remarkably stable spatial
      configuration. We explain the robust features of the model by the adjustable
      dynamics of its global loading-unloading cycle, which allows maintaining the long
      term stationary state without affecting the intrinsic avalanche dynamics.

PMID- 12005933
TI  - Off-equilibrium response function in the one-dimensional random-field Ising
      model.
AB  - A thorough numerical investigation of the slow dynamics in the d=1 random-field
      Ising model in the limit of an infinite ferromagnetic coupling is presented in
      this paper. Crossovers from the preasymptotic pure regime to the asymptotic Sinai
      regime are investigated for the average domain size, the autocorrelation
      function, and staggered magnetization. By switching on an additional small random
      field at the time t(w) the linear off-equilibrium response function is obtained,
      which displays as well the crossover from the nontrivial behavior of the d=1 pure
      Ising model to the asymptotic behavior where it vanishes identically.

PMID- 12005934
TI  - Critical structure factors of bilinear fields in O(N) vector models.
AB  - We compute the two-point correlation functions of general quadratic operators in
      the high-temperature phase of the three-dimensional O(N) vector model by using
      field-theoretical methods. In particular, we study the small- and large-momentum
      behavior of the corresponding scaling functions, and give general interpolation
      formulas based on a dispersive approach. Moreover, we determine the crossover
      exponent phi(T) associated with the traceless tensorial quadratic field, by
      computing and analyzing its six-loop perturbative expansion in fixed dimension.
      We find phi(T)=1.184(12), phi(T)=1.271(21), and phi(T)=1.40(4) for N=2,3,5,
      respectively.

PMID- 12005935
TI  - Classical kinetical Bose gas.
AB  - An autocatalytic reaction combined with spontaneous creation and annihilation
      processes of particles are studied in a quantum formalism of the master equation
      in a lattice gas representation with unrestricted occupancy. In case the system
      is activated by a linear coupling to a heat bath the problem can be solved
      exactly and the stationary particle density follows the Bose distribution. The
      relation to spin-flip processes with a restricted occupancy is discussed.
      Different from those processes the relaxation time and the density fluctuation
      increase in the high-temperature limit. On a small scale the mutual interaction
      between the particles is relevant. While in case of a repulsive interaction the
      stationary solution becomes unstable against short wavelength fluctuations, an
      attractive interaction leads to an instability for long wavelength fluctuations.
      The system decays in domains, the size of which can be estimated as a function of
      temperature and interaction strength. The model is also appropriate to study the
      growth of open bacterial colonies under the influence of a competitive
      interaction between the species.

PMID- 12005936
TI  - Phase ordering with a global conservation law: Ostwald ripening and coalescence.
AB  - Globally conserved phase ordering dynamics is investigated in systems with short
      range correlations at t=0. A Ginzburg-Landau equation with a global conservation
      law is employed as the phase field model. The conditions are found under which
      the sharp-interface limit of this equation is reducible to the area-preserving
      motion by curvature. Numerical simulations show that, for both critical and off
      critical quench, the equal-time pair correlation function exhibits dynamic
      scaling, and the characteristic coarsening length obeys l(t) approximately
      t(1/2). For the critical quench, our results are in excellent agreement with
      earlier results. For off-critical quench (Ostwald ripening) we investigate the
      dynamics of the size distribution function of the minority phase domains. The
      simulations show that, at large times, this distribution function has a self
      similar form with growth exponent 1/2. The scaled distribution, however, strongly
      differs from the classical Wagner distribution. We attribute this difference to
      coalescence of domains. A theory of Ostwald ripening is developed that takes into
      account binary coalescence events. The theoretical scaled distribution function
      agrees well with that obtained in the simulations.

PMID- 12005937
TI  - Upper bound for the time derivative of entropy for nonequilibrium stochastic
      processes.
AB  - We have shown how the intrinsic properties of a noise process can set an upper
      bound for the time derivative of entropy in a nonequilibrium system. The
      interplay of dissipation and the properties of noise processes driving the
      dynamical systems in presence and absence of external forces, reveals some
      interesting extremal nature of the upper bound.

PMID- 12005938
TI  - Grain boundary pinning and glassy dynamics in stripe phases.
AB  - We study numerically and analytically the coarsening of stripe phases in two
      spatial dimensions, and show that transient configurations do not achieve long
      ranged orientational order but rather evolve into glassy configurations with very
      slow dynamics. In the absence of thermal fluctuations, defects such as grain
      boundaries become pinned in an effective periodic potential that is induced by
      the underlying periodicity of the stripe pattern itself. Pinning arises without
      quenched disorder from the nonadiabatic coupling between the slowly varying
      envelope of the order parameter around a defect, and its fast variation over the
      stripe wavelength. The characteristic size of ordered domains asymptotes to a
      finite value R(g) approximately lambda(0)epsilon(-1/2)exp(absolute value of
      a/square root of epsilon), where epsilon<<1 is the dimensionless distance away
      from threshold, lambda(0) the stripe wavelength, and a a constant of order unity.
      Random fluctuations allow defect motion to resume until a new characteristic
      scale is reached, function of the intensity of the fluctuations. We finally
      discuss the relationship between defect pinning and the coarsening laws obtained
      in the intermediate time regime.

PMID- 12005939
TI  - Correlated disordered interactions on Potts models.
AB  - Using a weak-disorder scheme and real-space renormalization-group techniques, we
      obtain analytical results for the critical behavior of various q-state Potts
      models with correlated disordered exchange interactions along d(1) of d spatial
      dimensions on hierarchical (Migdal-Kadanoff) lattices. Our results indicate
      qualitative differences between the cases d-d(1)=1 (for which we find non
      physical random fixed points, suggesting the existence of non-perturbative fixed
      distributions) and d-d(1)>1 (for which we do find acceptable perturbative random
      fixed points), in agreement with previous numerical calculations by Andelman and
      Aharony [Phys. Rev. B 31, 4305 (1985)]. We also rederive a criterion for
      relevance of correlated disorder, which generalizes the usual Harris criterion.

PMID- 12005940
TI  - Correlation functions near modulated and rough surfaces.
AB  - In a system with long-ranged correlations, the behavior of correlation functions
      is sensitive to the presence of a boundary. We show that surface deformations
      strongly modify this behavior as compared to a flat surface. The modified near
      surface correlations can be measured by scattering probes. To determine these
      correlations, we develop a perturbative calculation in the deformations in height
      from a flat surface. Detailed results are given for a regularly patterned
      surface, as well as for a self-affinely rough surface with roughness exponent
      zeta. By combining this perturbative calculation in height deformations with the
      field-theoretic renormalization-group approach, we also estimate the values of
      critical exponents governing the behavior of the decay of correlation functions
      near a self-affinely rough surface. We find that for the interacting theory, a
      large enough zeta can lead to a different surface critical behavior. We also
      provide scaling relations between roughness induced critical exponents for
      thermodynamic surface quantities.

PMID- 12005941
TI  - Targeted free energy perturbation.
AB  - In this paper generalization of the free energy perturbation identity is derived,
      and a computational strategy based on this result is presented. A simple example
      illustrates the efficiency gains that can be achieved with this method.

PMID- 12005942
TI  - Nonequilibrium dynamics of the complex Ginzburg-Landau equation: numerical
      results in two and three dimensions.
AB  - This paper is the second of a two-stage exposition, in which we study the
      nonequilibrium dynamics of the complex Ginzburg-Landau (CGL) equation. We use
      spiral defects to characterize the system evolution and morphologies. In the
      first paper of this exposition [S.K. Das, S. Puri, and M.C. Cross, Phys. Rev E
      64, 046206 (2001)], we presented analytical results for the correlation function
      of a single spiral defect, and its short-distance singular behavior. We had also
      examined the utility of the Gaussian auxiliary field ansatz for characterizing
      multispiral morphologies. In this paper, we present results from an extensive
      numerical study of nonequilibrium dynamics in the CGL equation with
      dimensionality d=2,3. We discuss the behavior of domain growth laws; real-space
      correlation functions; and momentum-space structure factors. We also compare
      numerical results for the correlation functions and structure factors with
      analytical results presented in our first paper.

PMID- 12005943
TI  - Estimating probabilities from experimental frequencies.
AB  - Estimating the probability distribution q governing the behavior of a certain
      variable by sampling its value a finite number of times most typically involves
      an error. Successive measurements allow the construction of a histogram, or
      frequency count f, of each of the possible outcomes. In this work, the
      probability that the true distribution be q, given that the frequency count f was
      sampled, is studied. Such a probability may be written as a Gibbs distribution. A
      thermodynamic potential, which allows an easy evaluation of the mean Kullback
      Leibler divergence between the true and measured distribution, is defined. For a
      large number of samples, the expectation value of any function of q is expanded
      in powers of the inverse number of samples. As an example, the moments, the
      entropy, and the mutual information are analyzed.

PMID- 12005944
TI  - Geometrical properties of avalanches in self-organized critical models of solar
      flares.
AB  - We investigate the geometrical properties of avalanches in self-organized
      critical models of solar flares. Traditionally, such models differ from the
      classical sandpile model in their formulation of stability criteria in terms of
      the curvature of the nodal field, and belong to a distinct universality class.
      With a view toward comparing these properties to those inferred from spatially
      and temporally resolved flare observations, we consider the properties of
      avalanche peak snapshots, time-integrated avalanches in two and three dimensions,
      and the two-dimensional projections of the latter. The nature of the relationship
      between the avalanching volume and its projected area is an issue of particular
      interest in the solar flare context. Using our simulation results we investigate
      this relationship, and demonstrate that proper accounting of the fractal nature
      of avalanches can bring into agreement hitherto discrepant results of
      observational analyses based on simple, nonfractal geometries for the flaring
      volume.

PMID- 12005945
TI  - Flow properties of driven-diffusive lattice gases: theory and computer
      simulation.
AB  - We develop n-cluster mean-field theories (1 < or = n < or = 4) for calculating
      the flux and the gap distribution in the nonequilibrium steady states of the Katz
      Lebowitz-Spohn model of the driven diffusive lattice gas, with attractive and
      repulsive interparticle interactions, in both one and two dimensions for
      arbitrary particle densities, temperature as well as the driving field. We
      compare our theoretical results with the corresponding numerical data we have
      obtained from the computer simulations to demonstrate the level of accuracy of
      our theoretical predictions. We also compare our results with those for some
      other prototype models, notably particle-hopping models of vehicular traffic, to
      demonstrate the qualitative features we have observed in the Katz-Lebowitz-Spohn
      model, emphasizing, in particular, the consequences of repulsive interparticle
      interactions.

PMID- 12005946
TI  - Exact multipoint and multitime correlation functions of a one-dimensional model
      of adsorption and evaporation of dimers.
AB  - In this work, we provide a method that allows us to compute exactly the
      multipoint and multitime correlation functions of a one-dimensional stochastic
      model of dimer adsorption evaporation with random (uncorrelated) initial states.
      In particular, explicit expressions of the two-point non
      instantaneous/instantaneous correlation functions are obtained. The long-time
      behavior of these expressions is discussed in detail and in various physical
      regimes.

PMID- 12005947
TI  - Adaptation and survivors in a random Boolean network.
AB  - We introduce the competitive agent with imitation strategy in a random Boolean
      network, in which the agent plays a competitive game that rewards those in
      minority. After a long time interval, the worst performer changes its strategy to
      the one of the best and the process is repeated. The network, initially in a
      chaotic state, evolves to an intermittent state and finally reaches a frozen
      state. Time series of survived species (whose strategies are imitated by other
      agents) in the system depend on the connectivity of each agent. In a system with
      various connectivity groups, the low connectivity groups win the minority game
      over the high connectivity groups. We also compared the result with mutation
      strategy system.

PMID- 12005948
TI  - Statistics of level spacing of geometric resonances in random binary composites.
AB  - We study the statistics of level spacing of geometric resonances in the
      disordered binary networks. For a definite concentration p within the interval
      [0.2,0.7], numerical calculations indicate that the unfolded level spacing
      distribution P(t) and level number variance Sigma(2)(L) have general features. It
      is also shown that the short-range fluctuation P(t) and long-range spectral
      correlation Sigma(2)(L) lie between the profiles of the Poisson ensemble and
      Gaussion orthogonal ensemble. At the percolation threshold p(c), crossover
      behavior of functions P(t) and Sigma(2)(L) is obtained, giving the finite size
      scaling of mean level spacing delta and mean level number n, which obey the
      scaling laws, delta=1.032L(-1.952) and n=0.911L(1.970).

PMID- 12005949
TI  - Finite-size effect in the Eguiluz and Zimmermann model of herd formation and
      information transmission.
AB  - The Eguiluz and Zimmermann model of information transmission and herd formation
      in a financial market is studied analytically. Starting from a formal description
      on the rate of change of the system from one partition of agents in the system to
      another, a mean-field theory is systematically developed. The validity of the
      mean-field theory is carefully studied against fluctuations. When the number of
      agents N is sufficiently large and the probability of making a transaction a<<1/N
      ln N, finite-size effect is found to be significant. In this case, the system has
      a large probability of becoming a single cluster containing all the agents. For
      small clusters of agents, the cluster size distribution still obeys a power law
      but with a much reduced magnitude. The exponent is found to be modified to the
      value of -3 by the fluctuation effects from the value of -5/2 in the mean-field
      theory.

PMID- 12005950
TI  - Average entropy of a subsystem from its average Tsallis entropy.
AB  - In the non-extensive Tsallis scenario, Page's conjecture for the average entropy
      of a subsystem [Phys. Rev. Lett. 71, 1291 (1993)] as well as its demonstration
      are generalized, i.e., when a pure quantum system, whose Hilbert space dimension
      is mn, is considered, the average Tsallis entropy of an m-dimensional subsystem
      is obtained. This demonstration is expected to be useful to study systems where
      the usual entropy does not give satisfactory results.

PMID- 12005951
TI  - Variational theory for thermodynamics of thermal waves.
AB  - We discuss description of macroscopic representations of thermal fields with
      finite signal speed by composite variational principles involving suitably
      constructed potentials along with original physical variables. A variational
      formulation for a given vector field treats all field equations as constraints
      that are linked by Lagrange multipliers to the given kinetic potential. We focus
      on the example of simple hyperbolic heat transfer, but also stress that the
      approach can be easily extended to the coupled transfer of heat, mass, and
      electric charge. With our approach, various representations may be obtained for
      physical fields in terms of potentials (gradient or non-gradient
      representations). Corresponding Lagrangian and Hamiltonian formalism can be
      developed. Symmetry principles yield components of the energy-momentum tensor for
      the given kinetic potential. The limiting reversible case appears as a special
      yet suitable reference frame to describe irreversible phenomena. With the
      conservation laws resulting from the least action principle and the Gibbs
      equation, the variational scheme of nonequilibrium thermodynamics follows. Its
      main property is abandoning the assumption of local thermal equilibrium.

PMID- 12005952
TI  - Kink production in the presence of random distributed impurities.
AB  - Production of kinks during a quench in an overdamped regime of phi(4) model is
      investigated. An influence of random distributed impurities on defect production
      is studied.

PMID- 12005953
TI  - Remarks about the Tsallis formalism.
AB  - In the present paper the conditions for the validity of the Tsallis statistics
      are analyzed. The same has been done following the analogy with the traditional
      case: starting from the microcanonical description of the systems and taking into
      account their self-similarity scaling properties in the thermodynamic limit, it
      is analyzed the necessary conditions for the equivalence of microcanonical
      ensemble with the Tsallis generalization of the canonical ensemble. It is shown
      that the Tsallis statistics is appropriate for the macroscopic description of
      systems with potential scaling laws of the asymptotic accessible states density
      of the microcanonical ensemble. Our analysis shows many details of the Tsallis's
      formalism: the q-expectation values, the generalized Legendre transformations
      between the thermodynamic potentials, as well as the conditions for its validity,
      having a priori the possibility to estimate the value of the entropic index
      without the necessity of appealing to the computational simulations or the
      experiment. On the other hand, the definition of physical temperature received a
      modification that differs from the Toral result. For the case of finite systems,
      we have generalized the microcanonical thermostatistics of Gross with the
      generalization of the curvature tensor for this kind of description.

PMID- 12005954
TI  - Relaxation of nonspherical sessile drops towards equilibrium.
AB  - We present a theoretical study related to a recent experiment on the coalescence
      of sessile drops. The study deals with the kinetics of relaxation towards
      equilibrium, under the action of surface tension, of a spheroidal drop on a flat
      surface. For such a nonspherical drop under partial wetting conditions, the
      dynamic contact angle varies along the contact line. We propose a new nonlocal
      approach to the wetting dynamics, where the contact line velocity depends on the
      geometry of the whole drop. We compare our results to those of the conventional
      approach in which the contact line velocity depends only on the local value of
      the dynamic contact angle. The influence on drop dynamics of the pinning of the
      contact line by surface defects is also discussed.

PMID- 12005955
TI  - Slow relaxation in the large-N model for phase ordering.
AB  - The basic features of the slow relaxation phenomenology arising in phase ordering
      processes are obtained analytically in the large-N model through the exact
      separation of the order parameter into the sum of thermal and condensation
      components. The aging contribution in the response function chi(ag)(t,t(w)) is
      found to obey a pattern of behavior, under variation of dimensionality,
      qualitatively similar to the one observed in Ising systems. There exists a
      critical dimensionality (d=4) above which chi(ag)(t,t(w)) is proportional to the
      defect density rho(D)(t), while for d<4 it vanishes more slowly than rho(D)(t)
      and at d=2 does not vanish. As in the Ising case, this behavior can be understood
      in terms of the dependence on dimensionality of the interplay between the defect
      density and the effective response associated to a single defect.

PMID- 12005956
TI  - Analysis of the infinity-replica symmetry breaking solution of the Sherrington
      Kirkpatrick model.
AB  - In this work we analyze the Parisi infinity-replica symmetry breaking solution of
      the Sherrington-Kirkpatrick model without external field using high order
      perturbative expansions. The predictions are compared with those obtained from
      the numerical solution of the infinity-replica symmetry breaking equations, which
      are solved using a pseudospectral code that allows for very accurate results.
      With these methods we are able to get more insight into the analytical properties
      of the solutions. We are also able to determine numerically the end point x(max)
      of the plateau of q(x) and find that lim(T-->0)x(max)(T)>0.5.

PMID- 12005957
TI  - Empirical macroscopic features of spatial-temporal traffic patterns at highway
      bottlenecks.
AB  - Results of an empirical study of congested patterns measured during 1995-2001 at
      German highways are presented. Based on this study, various types of congested
      patterns at on and off ramps have been identified, their macroscopic spatial
      temporal features have been derived, and an evolution of those patterns and
      transformations between different types of the patterns over time has been found
      out. It has been found that at an isolated bottleneck (a bottleneck that is far
      enough from other effective bottlenecks) either the general pattern (GP) or the
      synchronized flow pattern (SP) can be formed. In GP, synchronized flow occurs and
      wide moving jams spontaneously emerge in that synchronized flow. In SP, no wide
      moving jams emerge, i.e., SP consists of synchronized flow only. An evolution of
      GP into SP when the flow rate to the on ramp decreases has been found and
      investigated. Spatial-temporal features of complex patterns that occur if two or
      more effective bottlenecks exist on a highway have been found out. In particular,
      the expanded pattern where synchronized flow covers two or more effective
      bottlenecks can be formed. It has been found that the spatial-temporal structure
      of congested patterns possesses predictable, i.e., characteristic, unique, and
      reproducible features, for example, the most probable types of patterns that are
      formed at a given bottleneck. According to the empirical investigations the cases
      of the weak and the strong congestion should be distinguished. In contrast to the
      weak congestion, the strong congestion possesses the following characteristic
      features: (i) the flow rate in synchronized flow is self-maintaining near a limit
      flow rate; (ii) the mean width of the region of synchronized flow in GP does not
      depend on traffic demand; (iii) there is a correlation between the parameters of
      synchronized flow and wide moving jams: the higher the flow rate out from a wide
      moving jam is, the higher is the limit flow rate in the synchronized flow. The
      strong congestion often occurs in GP whereas the weak congestion is usual for SP.
      The weak congestion is often observed at off ramps whereas the strong congestion
      much more often occurs at on ramps. Under the weak congestion diverse
      transformations between different congested patterns can occur.

PMID- 12005958
TI  - Universal pulse shape scaling function and exponents: critical test for avalanche
      models applied to Barkhausen noise.
AB  - In order to test if the universal aspects of Barkhausen noise in magnetic
      materials can be predicted from recent variants of the nonequilibrium zero
      temperature Random Field Ising Model, we perform a quantitative study of the
      universal scaling function derived from the Barkhausen pulse shape in simulations
      and experiment. Through data collapses and scaling relations we determine the
      critical exponents tau and 1/sigma nu z in both simulation and experiment.
      Although we find agreement in the critical exponents, we find differences between
      theoretical and experimental pulse shape scaling functions as well as between
      different experiments.

PMID- 12005959
TI  - Roughness distributions for 1/f alpha signals.
AB  - The probability density function (PDF) of the roughness, i.e., of the temporal
      variance, of 1/f(alpha) noise signals is studied. Our starting point is the
      generalization of the model of Gaussian, time periodic, 1/f noise, discussed in
      our recent Letter [Phys. Rev. Lett. 87, 240601 (2001)], to arbitrary power law.
      We investigate three main scaling regions (alpha < or = 1/2, 1/2 < alpha < or =
      1, and 1< alpha), distinguished by the scaling of the cumulants in terms of the
      microscopic scale and the total length of the period. Various analytical
      representations of the PDF allow for a precise numerical evaluation of the
      scaling function of the PDF for any alpha. A simulation of the periodic process
      makes it possible to study also nonperiodic, thus experimentally more relevant,
      signals on relatively short intervals embedded in the full period. We find that
      for alpha < or = 1/2 the scaled PDFs in both the periodic and the nonperiodic
      cases are Gaussian, but for alpha > 1/2 they differ from the Gaussian and from
      each other. Both deviations increase with growing alpha. That conclusion, based
      on numerics, is reinforced by analytic results for alpha = 2 and alpha-
      >infinity, in the latter limit the scaling function of the PDF being finite for
      periodic signals, but developing a singularity for the aperiodic ones. Finally,
      an overview is given for the scaling of cumulants of the roughness and the
      various scaling regions in arbitrary dimensions. We suggest that our theoretical
      and numerical results open a different perspective on the data analysis of
      1/f(alpha) processes.

PMID- 12005960
TI  - Self-organized criticality: robustness of scaling exponents.
AB  - We investigate a deterministic, conservative, undirected, critical height
      sandpile model with dissipation of an energy at boundaries that can simulate
      avalanche dynamics. It was derived from the Bak-Tang-Wiesenfeld model [P. Bak, C.
      Tang, and K. Wiesenfeld, Phys. Rev. Lett. 59, 381 (1987)] introducing an
      additional second-higher threshold so the model has two distinct thresholds. Our
      computer simulations for a two-dimensional lattice show that scaling properties
      of the model depend on the higher-threshold values and site concentrations. These
      results are not therefore consistent with the present self-organized criticality
      hypothesis where the scaling properties are independent of the model parameters.

PMID- 12005961
TI  - Solvable Markov random field model in color image restoration.
AB  - We propose a scheme for image restoration of full color images by means of a
      solvable probabilistic model in the red-green-blue space. A special case of our
      solvable probabilistic model is equivalent to a multicomponent Gaussian model in
      the statistical mechanics. Exact closed expressions of the evidence and the
      expectation value of intensity at each pixel in our solvable probabilistic model
      can be obtained by using multidimensional Gaussian integral formulas and a
      discrete Fourier transform. In the present paper, the degradation process is
      assumed to be an additive white Gaussian noise. Hyperparameters are determined so
      as to maximize the evidence that is expressed in terms of the partition function
      in our solvable probabilistic model. This work is a pioneering work for the
      Bayesian approach to the color image restoration by means of the statistical
      mechanical technique.

PMID- 12005962
TI  - Effect of angular momentum on equilibrium properties of a self-gravitating
      system.
AB  - The microcanonical properties of a two-dimensional system of N classical
      particles interacting via a smoothed Newtonian potential, as a function of the
      total energy E and the total angular momentum L, are discussed. The two first
      moments of the distribution of the linear momentum of a given particle at a fixed
      position show that (a) on average the system rotates like a solid body and (b)
      the velocity dispersion is a function of the distance from the center. In order
      to estimate suitable observables, a numerical method based on an importance
      sampling algorithm is presented. The entropy surface S shows a negative specific
      heat capacity region at fixed L for all L. Observables probing the average mass
      distribution are used to understand the link between thermostatistical properties
      and the spatial distribution of particles. In order to define a phase in a
      nonextensive system, we introduce a more general observable than that proposed by
      Gross and Votyakov [Eur. Phys. J. B 15, 115 (2000)]. This observable is the sign
      of the largest eigenvalue of the Hessian matrix of the entropy surface. If it is
      negative then the system is in a pure (single) phase; if it is positive then the
      system undergoes a first order phase transition. At large E the gravitational
      system is in a homogeneous gas phase. At low E there are several collapse phases.
      At L=0 there is a single-cluster phase and for L not equal 0 there are several
      phases with two clusters. The relative size of the clusters depends on L. All
      these pure phases are separated by a first order phase transition region. Signals
      of critical behavior emerge at several points of the parameter space (E,L). We
      also show that a huge loss of information appears if we treat the system as a
      function of the intensive parameters. Besides the known nonequivalence at first
      order phase transitions, the pure phases with two clusters of different sizes are
      not accessible to the canonical ensemble. Moreover, for a particular choice of
      intensive parameters introduced in this paper, there exist in the microcanonical
      ensemble some values of those intensive parameters for which the corresponding
      canonical ensemble does not exist, i.e., the partition sum diverges.

PMID- 12005963
TI  - Iterated conformal dynamics and Laplacian growth.
AB  - The method of iterated conformal maps for the study of diffusion limited
      aggregates (DLA) is generalized to the study of Laplacian growth patterns and
      related processes. We emphasize the fundamental difference between these
      processes: DLA is grown serially with constant size particles, while Laplacian
      patterns are grown by advancing each boundary point in parallel, proportional to
      the gradient of the Laplacian field. We introduce a two-parameter family of
      growth patterns that interpolates between DLA and a discrete version of Laplacian
      growth. The ultraviolet putative finite-time singularities are regularized here
      by a minimal tip size, equivalently for all the models in this family. With this
      we stress that the difference between DLA and Laplacian growth is not in the
      manner of ultraviolet regularization, but rather in their deeply different growth
      rules. The fractal dimensions of the asymptotic patterns depend continuously on
      the two parameters of the family, giving rise to a "phase diagram" in which DLA
      and discretized Laplacian growth are at the extreme ends. In particular, we show
      that the fractal dimension of Laplacian growth patterns is higher than the
      fractal dimension of DLA, with the possibility of dimension 2 for the former not
      excluded.

PMID- 12005964
TI  - Out-of-equilibrium thermodynamic relations in systems with aging and slow
      relaxation.
AB  - The experimental time scale dependence of thermodynamic relations in out-of
      equilibrium systems with aging phenomena is investigated theoretically by using
      only aging properties of the two-time correlation functions and the generalized
      fluctuation-dissipation theorem. We show that there are two experimental time
      regimes characterized by different thermal properties. In the first regime where
      the waiting time is much longer than the measurement time, the principle of
      minimum work holds even though a system is out of equilibrium. In the second
      regime where both the measurement time and the waiting time are long, the thermal
      properties are completely different from properties in equilibrium. For the
      single-correlation-scale systems such as p-spin spherical spin glasses, contrary
      to a fundamental assumption of thermodynamics, the work done in an infinitely
      slow operation depends on the path of change of the external field even when the
      waiting time is infinite. On the other hand, for the multi-correlation-scale
      systems such as Sherrington-Kirkpatrick model, the work done in an infinitely
      slow operation is independent of the path. Our results imply that in order to
      describe thermodynamic properties of systems with aging it is essential to
      consider the experimental time scales and history of a system as a state variable
      is necessary.

PMID- 12005965
TI  - Critical behavior of a strain percolation model for metals.
AB  - Extensive simulations of a strain percolation model for a deforming metal have
      been performed to examine its strain behavior. We find that the total strain
      exhibits critical power-law behavior that is well explained by two-dimensional
      percolation theory. Near the critical point, most of the strained cells organize
      themselves around a state having the minimum or at least marginally stable strain
      regardless of the initial conditions. A strain much greater than the minimum
      stable strain generally decays to a lower value when transmitted to an unstrained
      cell. The universal behavior of the total strain in the system is a consequence
      of the self-organizing character of the strain in the critical cluster. Although
      the probability distributions for the total strain and cluster size appear to
      exhibit nonuniversal behavior, this may merely represent a transient response
      before crossover to a true asymptotic, universal behavior occurs. Other critical
      aspects of the model are also discussed.

PMID- 12005966
TI  - Stable propagation of an ordered array of cracks during directional drying.
AB  - We study the appearance and evolution of an array of parallel cracks in a thin
      slab of material that is directionally dried, and show that the cracks penetrate
      the material uniformly if the drying front is sufficiently sharp. We also show
      that cracks have a tendency to become evenly spaced during the penetration. The
      typical distance between cracks is mainly governed by the typical distance of the
      pattern at the surface, and it is not modified during the penetration. Our
      results agree with recent experimental work, and can be extended to three
      dimensions to describe the properties of columnar polygonal patterns observed in
      some geological formations.

PMID- 12005967
TI  - Fracture model with variable range of interaction.
AB  - We introduce a fiber bundle model where the interaction among fibers is modeled
      by an adjustable stress-transfer function that can interpolate between the two
      limiting cases of load redistribution, i.e., the global and the local load
      sharing schemes. By varying the range of interaction, several features of the
      model are numerically studied and a crossover from mean-field to short-range
      behavior is obtained. The properties of the two regimes and the emergence of the
      crossover in between are explored by numerically studying the dependence of the
      ultimate strength of the material on the system size, the distribution of
      avalanches of breakings, and of the cluster sizes of broken fibers. Finally, we
      analyze the moments of the cluster size distributions to accurately determine the
      value at which the crossover is observed.

PMID- 12005968
TI  - Autoregressive processes with exponentially decaying probability distribution
      functions: applications to daily variations of a stock market index.
AB  - We consider autoregressive conditional heteroskedasticity (ARCH) processes in
      which the variance sigma(2)(y) depends linearly on the absolute value of the
      random variable y as sigma(2)(y) = a+b absolute value of y. While for the
      standard model, where sigma(2)(y) = a + b y(2), the corresponding probability
      distribution function (PDF) P(y) decays as a power law for absolute value of y-
      >infinity, in the linear case it decays exponentially as P(y) approximately exp(
      alpha absolute value of y), with alpha = 2/b. We extend these results to the more
      general case sigma(2)(y) = a+b absolute value of y(q), with 0 < q < 2. We find
      stretched exponential decay for 1 < q < 2 and stretched Gaussian behavior for 0 <
      q < 1. As an application, we consider the case q=1 as our starting scheme for
      modeling the PDF of daily (logarithmic) variations in the Dow Jones stock market
      index. When the history of the ARCH process is taken into account, the resulting
      PDF becomes a stretched exponential even for q = 1, with a stretched exponent
      beta = 2/3, in a much better agreement with the empirical data.

PMID- 12005969
TI  - Scaling behavior of the order parameter and its conjugated field in an absorbing
      phase transition around the upper critical dimension.
AB  - We analyze numerically the critical behavior of an absorbing phase transition in
      a conserved lattice gas in an external field. The external field is realized as a
      spontaneous creation of active particles that drives the system away from
      criticality. Nevertheless, the order parameter obeys certain scaling laws for
      sufficiently small external fields. These scaling laws are investigated and the
      corresponding exponents are determined in various dimensions (D=2,3,4,5). At the
      so-called upper critical dimension D(c)=4 one has to modify the usual scaling
      laws by logarithmic corrections.

PMID- 12005970
TI  - Collective motions in globally coupled tent maps with stochastic updating.
AB  - We study a generalization of globally coupled maps, where the elements are
      updated with probability p. When p is below a threshold p(c), the collective
      motion vanishes and the system is the stationary state in the large size limit.
      We present the linear stability analysis.

PMID- 12005971
TI  - Stabilization of stationary excitation pulses in an open flow without long-range
      inhibition.
AB  - We study numerically and experimentally the stabilization of stationary
      excitation pulses in an open flow system. Since all the species have equal flow
      and diffusion coefficients, stabilization of stationary pulses by long-range
      inhibition is excluded. Upstream propagating pulses slow down as they approach
      the inflow boundary, where a constant forcing establishes a downstream extending
      subexcitable boundary layer. When the flow velocity is low, successive pulses
      vanish as they reach the subexcitable region. When the flow velocity is
      increased, the incoming pulses pile up near the inflow one after the other to
      form a stationary and space-periodic structure. This occurs in such a manner that
      the system remembers and stores the number of incoming pulses. We show that flow
      induced stabilization of stationary pulses involves a mechanism by which the
      upstream subexcitable region and the flow cause the arrest of the pulse front and
      the pulse back, respectively. We discuss how the flow-stabilized structures
      compare to, and are different from those stabilized by a long-ranged, diffusive
      inhibition and from those observed in boundary-forced open flows of media showing
      relaxation-type oscillations.

PMID- 12005972
TI  - Diffusion entropy and waiting time statistics of hard-x-ray solar flares.
AB  - We show at work a technique of scaling detection based on evaluating the Shannon
      entropy of the diffusion process obtained by converting the time series under
      study into trajectories. This method, called diffusion entropy, affords
      information that cannot be derived from the direct evaluation of waiting times.
      We apply this method to the analysis of the distribution of time distance tau
      between two nearest-neighbor solar flares. This traditional part of the analysis
      is based on the direct evaluation of the distribution function psi(tau), or of
      the probability Psi(tau), that no time distance smaller than a given tau is
      found. We adopt the paradigm of the inverse power-law behavior, and we focus on
      the determination of the inverse power index mu, without ruling out different
      asymptotic properties that might be revealed, at larger scales, with the help of
      richer statistics. We then use the DE method, with three different walking rules,
      and we focus on the regime of transition to scaling. This regime of transition
      and the value of the scaling parameter itself, delta, depends on the walking rule
      adopted, a property of interest to shed light on the slow process of transition
      from dynamics to thermodynamics often occurring under anomalous statistical
      conditions. With the first two rules the transition regime occurs throughout a
      large time interval, and the information contained in the time series is
      transmitted, to a great extent, to it, as well as to the scaling regime. By using
      the third rule, on the contrary, the same information is essentially conveyed to
      the scaling regime, which, in fact, emerges very quickly after a fast transition
      process. We show that the DE method not only causes to emerge the long-range
      correlation with a given mu < 3, and so a basin of attraction different from the
      ordinary Gaussian one, but it also reveals the presence of memory effects induced
      by the time dependence of the solar flare rate. When this memory is annihilated
      by shuffling, the scaling parameter delta is shown to fit the theoretically
      expected function of mu. All this leads us to the compelling conclusion that mu =
      2.138+/-0.01.

PMID- 12005973
TI  - Chaotic scattering in deformed optical microlasing cavities.
AB  - We consider a common class of dielectric optical microlasing cavities with
      quadrupolar deformations and address the question of the maximally allowed amount
      of deformation for both high-Q operation and a high degree of directionality of
      light emission. Our approach is to compute the probability for light rays to be
      trapped in the cavity by examining chaotic scattering dynamics in the classical
      phase space. We develop a dynamical criterion for high-Q operation and introduce
      a measure to quantify the directionality of the light emission. Our results
      suggest that high-Q and directionality can be achieved simultaneously in a wide
      range of the deformation parameter.

PMID- 12005974
TI  - Lorenz-like systems and classical dynamical equations with memory forcing: an
      alternate point of view for singling out the origin of chaos.
AB  - An alternate view for the emergence of chaos in Lorenz-like systems is presented
      in this paper. For such purpose, the Lorenz problem is reformulated in a
      classical mechanical form and it turns out to be equivalent to the problem of a
      damped and forced one-dimensional motion of a particle in a two-well potential,
      with a forcing term depending on the "memory" of the particle past motion. The
      dynamics of the original Lorenz system in the proposed particle phase space can
      then be rewritten in terms of a one-dimensional first-exit-time problem. The
      emergence of chaos turns out to be due to the discontinuous solutions of the
      transcendental equation ruling the time for the particle to cross the
      intermediate potential wall. The whole problem is tackled analytically deriving a
      piecewise linearized Lorenz-like system that preserves all the essential
      properties of the original model.

PMID- 12005975
TI  - Effect of colored noises on spatiotemporal chaos in the complex Ginzburg-Landau
      equation.
AB  - The effect of colored noises, which are correlated both in space and time, on
      spatiotemporal chaos in the complex Ginzburg-Landau equation has been studied
      numerically. The correlations of spatiotemporal patterns as a function of
      characteristics of noise were calculated. We found that there exists an optimal
      correlation length of noise where the system establishes its maximal spatial
      correlation; a small temporal correlation of noise corresponds to a larger
      correlation length in the system; and that an increase of noise intensity
      enhances the spatial correlation of the spatiotemporal patterns. Besides, the
      frequency of temporal correlation function, which is a complicated oscillation,
      also depends on properties of the noise.

PMID- 12005976
TI  - Unusual spiral wave tip trajectories in a parametrically forced nonequilibrium
      system.
AB  - The effect of parametric modulations on spiral waves that form in a thin layer of
      liquid crystal under rotating magnetic field is studied in laboratory experiments
      and numerical simulations. Parametric forcings that are sinusoidal in time make a
      simply rotating spiral tip to meander, rendering a compound tip trajectory that
      is composed of a main circular orbit and a satellite orbit with an unusual
      crescent shape. No evidence of frequency locking is found. The underlying
      mechanism for the unusual shape of the satellite orbit is elucidated, and the
      dependence of the rotation frequency of the main circular orbit f(o) on the
      perturbation parameters are discussed.

PMID- 12005977
TI  - Harmonic forcing of an extended oscillatory system: homogeneous and periodic
      solutions.
AB  - In this paper we study the effect of external harmonic forcing on a one
      dimensional oscillatory system described by the complex Ginzburg-Landau equation
      (CGLE). For a sufficiently large forcing amplitude, a homogeneous state with no
      spatial structure is observed. The state becomes unstable to a spatially periodic
      "stripe" state via a supercritical bifurcation as the forcing amplitude
      decreases. An approximate phase equation is derived, and an analytic solution for
      the stripe state is obtained, through which the asymmetric behavior of the
      stability border of the state is explained. The phase equation, in particular the
      analytic solution, is found to be very useful in understanding the stability
      borders of the homogeneous and stripe states of the forced CGLE.

PMID- 12005978
TI  - Measuring the Lyapunov exponent using quantum mechanics.
AB  - We study the time evolution of two wave packets prepared at the same initial
      state, but evolving under slightly different Hamiltonians. For chaotic systems,
      we determine the circumstances that lead to an exponential decay with time of the
      wave packet overlap function. We show that for sufficiently weak perturbations,
      the exponential decay follows a Fermi golden rule, while by making the difference
      between the two Hamiltonians larger, the characteristic exponential decay time
      becomes the Lyapunov exponent of the classical system. We illustrate our
      theoretical findings by investigating numerically the overlap decay function of a
      two-dimensional dynamical system.

PMID- 12005979
TI  - Synchronizing chaotic dynamics with uncertainties based on a sliding mode control
      design.
AB  - The synchronization of two chaotic systems with uncertainties is studied in this
      paper. A feedback controller is provided based on a sliding mode control design.
      A kind of extended state observer is used to compensate for the systems'
      uncertainties, such as the structure difference or parameter mismatching, using
      only the available synchronizing error. Then the feedback controller becomes
      physically realizable based on the states of the observer, and can be used to
      synchronize two continuous chaotic systems. Illustrative examples of the
      synchronization of Duffing and Van der Pol oscillators as well as two Lorenz
      systems with parameter mismatching are proposed to show the effectiveness of this
      method.

PMID- 12005980
TI  - Anderson localized state as a predissipative state: irreversible emission of
      thermalized quanta from a dynamically delocalized state.
AB  - It was shown that localization in one-dimensional disordered (quantum) electronic
      system is destroyed against coherent harmonic perturbations and the delocalized
      electron exhibits an unlimited diffusive motion [Yamada and Ikeda, Phys. Rev. E
      59, 5214 (1999)]. The appearance of diffusion implies that the system has
      potential for irreversibility and dissipation. In the present paper, we
      investigate dissipative property of the dynamically delocalized state, and we
      show that an irreversible quasistationary energy flow indeed appears in the form
      of a "heat" flow when we couple the system with another dynamical degree of
      freedom. In the concrete we numerically investigate dissipative properties of a
      one-dimensional tight-binding electronic system perturbed by time-dependent
      harmonic forces, by coupling it with a quantum harmonic oscillator or a quantum
      anharmonic oscillator. It is demonstrated that if the on-site potential is
      spatially irregular an irreversible energy transfer from the scattered electron
      to the test oscillator occurs. Moreover, the test oscillator promptly approaches
      a thermalized state characterized by a well-defined time-dependent temperature.
      On the contrary, such a relaxation process cannot be observed at all for periodic
      potential systems. Our system is one of the minimal quantum systems in which a
      distinct nonequilibrium statistical behavior is self-induced.

PMID- 12005981
TI  - Neural networks for estimating intrinsic dimension.
AB  - We consider the problem of feature extraction and determination of intrinsic
      dimensionality of observation data. One of the common approaches to this problem
      is to use autoassociative neural networks with a "bottleneck" projecting layer.
      We propose a different approach in which a neural network performs a topological
      mapping that creates a nonlinear lower-dimensional projection of the data. The
      mapping preserves relative distances of neighbors. This technique can be
      efficiently implemented with the help of radial basis function networks, and it
      is significantly faster than training an autoassotiative network. We show that
      the proposed technique can be used for estimating the dimension of minimal
      mathematical model from time series data.

PMID- 12005982
TI  - Synchronization of coupled assemblies of relaxation oscillatory electrode pairs.
AB  - Spatiotemporal patterns emerging through coupling of identical relaxation
      oscillatory electrode pairs are studied. Each pair, consisting of an iron anode
      and a copper cathode, oscillates periodically under fixed applied potential
      difference conditions. It is shown that the system synchronizes rapidly (within
      few oscillatory cycles) and differences of natural frequencies as well as
      boundary effects are compensated. The effect of the geometrical configuration on
      the dynamic modes is investigated for relatively large assemblies of such
      oscillatory pairs. When oscillators are coupled through neighboring electrodes,
      the response is synchronized by a simultaneous formation of groups. The formation
      of groups due to enhancement or inhibition of the oscillations depends on the
      relative position of interacting anodes and cathodes. The behavior of the system
      is compared with the response of coupled relaxation cells of neurophysiological
      interest.

PMID- 12005983
TI  - Diffusion in a periodically driven damped and undamped pendulum.
AB  - We study the diffusion process in a periodically driven damped and undamped
      pendulum. The effect of angular frequency omega of the external periodic force on
      the diffusion process is investigated. We show the occurrence of normal and
      anomalous diffusions in the undamped system. In the presence of damping, normal
      chaotic diffusion is found. Near certain bifurcation points, the phase velocity
      is found to be intermittent and the diffusion coefficient is found to exhibit
      power-law divergence. We argue that the divergence of the diffusion coefficient
      near the bifurcation points is similar to that of the average laminar lengths
      near them. The effect of bias on the dynamics is also discussed.

PMID- 12005984
TI  - Lyapunov exponents, noise-induced synchronization, and Parrondo's paradox.
AB  - We show that Lyapunov exponents of a stochastic system, when computed for a
      specific realization of the noise process, are related to conditional Lyapunov
      exponents in deterministic systems. We propose to use the term stochastically
      induced regularity instead of noise-induced synchronization and explain the
      reason why. The nature of stochastically induced regularity is discussed: in some
      instances, it is a dynamical analog of Parrondo's paradox.

PMID- 12005985
TI  - Jets, stickiness, and anomalous transport.
AB  - Dynamical and statistical properties of the vortex and passive particle advection
      in chaotic flows generated by 4- and 16-point vortices are investigated. General
      transport properties of these flows are found to be anomalous and exhibit a
      superdiffusive behavior with typical second moment exponent mu approximately
      1.75. The origin of this anomaly is traced to the presence of coherent structures
      within the flow, the vortex cores, and the region far from where vortices are
      located. In the vicinity of these regions stickiness is observed and the motion
      of tracers is quasiballistic. The chaotic nature of the underlying flow dictates
      the choice for thorough analysis of transport properties. Passive tracer motion
      is analyzed by measuring the mutual relative evolution of two nearby tracers.
      Some tracers travel in each other's vicinity for relatively long times. This is
      related to a hidden order for the tracers, which we call jets. Jets are localized
      and found in sticky regions. Their structure is analyzed and found to be formed
      of a nested set of jets within jets. The analysis of the jet trapping time
      statistics shows a quantitative agreement with the observed transport exponent.

PMID- 12005986
TI  - Spectral properties of quantized barrier billiards.
AB  - The properties of energy levels in a family of classically pseudointegrable
      systems, the barrier billiards, are investigated. An extensive numerical study of
      nearest-neighbor spacing distributions, next-to-nearest spacing distributions,
      number variances, spectral form factors, and the level dynamics is carried out.
      For a special member of the billiard family, the form factor is calculated
      analytically for small arguments in the diagonal approximation. All results
      together are consistent with the so-called semi-Poisson statistics.

PMID- 12005987
TI  - Traveling concentric-roll patterns in Rayleigh-Benard convection with modulated
      rotation.
AB  - We present experimental results for pattern formation in Rayleigh-Benard
      convection with modulated rotation about a vertical axis. The dimensionless
      rotation rate Omega was varied as Omega(m)=Omega[1+delta cos(phi Omega t)] (time
      is scaled by the vertical viscous diffusion time of the cell). We used a
      cylindrical cell of aspect ratio (radius/height) Gamma=11.8 and varied Omega,
      delta, phi, and epsilon identical with R/R(c)(Omega)-1 (R is the Rayleigh
      number). The fluid was water with a Prandtl number of 4.5. Sufficiently far above
      onset even a small delta greater than approximately 0.02 stabilized a concentric
      roll (target) pattern. Multiarmed spirals were observed close to onset. The rolls
      of the target patterns traveled radially inward independent of the sense of
      rotation. The radial speed v was nearly independent of epsilon for fixed Omega,
      delta, and phi. However, v increased with any one of Omega, delta, and phi when
      all the other parameters were held fixed.

PMID- 12005988
TI  - Rotating convection in an anisotropic system.
AB  - We study the stability of patterns arising in rotating convection in weakly
      anisotropic systems using a modified Swift-Hohenberg equation. The anisotropy,
      either an endogenous characteristic of the system or induced by external forcing,
      can stabilize periodic rolls in the Kuppers-Lortz chaotic regime. We apply this
      to the particular case of rotating convection with time-modulated rotation where
      recently, in experiment, spiral and target patterns have been observed in
      otherwise Kuppers-Lortz-unstable regimes. We show how the underlying base flow
      breaks the isotropy, thereby affecting the linear growth rate of convection rolls
      in such a way as to stabilize spirals and targets. Throughout we compare
      analytical results to numerical simulations of the Swift-Hohenberg equation.

PMID- 12005989
TI  - Dynamic separation of chaotic signals in the presence of noise.
AB  - The problem of separation of a noise-contaminated observed sum of chaotic signals
      into the individual components is considered. A noise threshold is found above
      which high-quality separation is impossible. Below the threshold, each signal is
      recovered with any prescribed accuracy with a separation method. The threshold
      effect is shown to be associated with the information content of chaotic signals
      and a theoretical estimate is given for the threshold.

PMID- 12005990
TI  - Skew-orthogonal polynomials and random-matrix ensembles.
AB  - There is considerable interest in understanding the relation between random
      matrix ensembles and quantum chaotic systems in the context of the universality
      of energy-level correlations. In this connection, while Gaussian ensembles of
      random matrices have been studied extensively, not much is known about ensembles
      with non-Gaussian weight functions. Dyson has shown that the n-level correlation
      functions can be expressed in terms of a kernel function involving orthogonal and
      skew-orthogonal polynomials--orthogonal for matrix ensembles with unitary
      invariance and skew orthogonal for ensembles with orthogonal and symplectic
      invariances. We have obtained the following results. (1) Skew-orthogonal
      polynomials of both types are derived for the Jacobi class of weight functions
      including the limiting cases of associated Laguerre and Hermite (or Gaussian).
      (2) Matrix-integral representations are given for the general weight functions.
      (3) Asymptotic forms of the polynomials are obtained rigorously for the Jacobi
      class and in the form of an ansatz for the general case. (4) For the three types
      of ensembles, the (asymptotic) n-level correlation functions with appropriate
      scaling are shown to be universal, being independent of the weight function and
      location in the spectrum, and identical with the well-known Gaussian results.
      This provides a rigorous justification for the universality of the Gaussian
      ensemble results observed in quantum chaotic systems. As expected, the level
      density is not universal.

PMID- 12005991
TI  - Exact, convergent periodic-orbit expansions of individual energy eigenvalues of
      regular quantum graphs.
AB  - We present exact, explicit, convergent periodic-orbit expansions for individual
      energy levels of regular quantum graphs in the paper. One simple application is
      the energy levels of a particle in a piecewise constant potential. Since the
      classical ray trajectories (including ray splitting) in such systems are strongly
      chaotic, this result provides an explicit quantization of a classically chaotic
      system.

PMID- 12005992
TI  - Acceleration effect of coupled oscillator systems.
AB  - We have developed a curved isochron clock (CIC) by modifying the radial isochron
      clock to provide a clean example of the acceleration (deceleration) effect. By
      analyzing a two-body system of coupled CICs, we determined that an unbalanced
      mutual interaction caused by curved isochron sets is the minimum mechanism needed
      for generating the acceleration (deceleration) effect in coupled oscillator
      systems. From this we can see that the Sakaguchi and Kuramoto (SK) model, which
      is a class of nonfrustrated mean field model, has an acceleration (deceleration)
      effect mechanism. To study frustrated coupled oscillator systems, we extended the
      SK model to two oscillator associative memory models, one with symmetric and the
      other with asymmetric dilution of coupling, which also have the minimum mechanism
      of the acceleration (deceleration) effect. We theoretically found that the
      Onsager reaction term (ORT), which is unique to frustrated systems, plays an
      important role in the acceleration (deceleration) effect. These two models are
      ideal for evaluating the effect of the ORT because, with the exception of the
      ORT, they have the same order parameter equations. We found that the two models
      have identical macroscopic properties, except for the acceleration effect caused
      by the ORT. By comparing the results of the two models, we can extract the effect
      of the ORT from only the rotation speeds of the oscillators.

PMID- 12005993
TI  - Shock structures and bunching fronts in excitable reaction-diffusion systems.
AB  - We report experimental results on the dynamics of excitation waves in a modified
      Belousov-Zhabotinsky reaction. The waves in this system obey nonmonotonic
      dispersion relations. This anomaly induces the stacking of excitation fronts into
      patterns with stable interpulse distances. The stacking process creates either a
      traveling shock structure or a cascade of bunching events in which metastable
      wave packets are formed. The direction and the speed of the shock are explained
      in terms of a simple geometrical analysis. We also present experimental evidence
      for the corresponding instabilities in two-dimensional systems. Here, wave
      stacking generates atypical structures in the collision of target patterns and
      wave bunching is accompanied by complex front deformations.

PMID- 12005994
TI  - Limits to the experimental detection of nonlinear synchrony.
AB  - Chaos synchronization is often characterized by the existence of a continuous
      function between the states of the components. However, in coupled systems
      without inherent symmetries, the synchronization set can be extremely
      complicated. We describe and illustrate three typical complications that can
      arise, and we discuss how existing methods for detecting synchronization will be
      hampered by the presence of these features.

PMID- 12005995
TI  - Decoherence for classically chaotic quantum maps.
AB  - We study the behavior of an open quantum system, with an N-dimensional space of
      states, whose density matrix evolves according to a nonunitary map defined in two
      steps: A unitary step, where the system evolves with an evolution operator
      obtained by quantizing a classically chaotic map (baker's map and Harper's map
      are the two examples we consider). A nonunitary step where the evolution operator
      for the density matrix mimics the effect of diffusion in the semiclassical (large
      N) limit. The process of decoherence and the transition from quantum to classical
      behavior are analyzed in detail by means of numerical and analytic tools. The
      existence of a regime where the entropy grows with a rate that is independent of
      the strength of the diffusion coefficient is demonstrated. The nature of the
      processes that determine the production of entropy is analyzed.

PMID- 12005996
TI  - Mode locking of spatiotemporally periodic orbits in coupled sine circle map
      lattices.
AB  - We study the organization of mode-locked intervals corresponding to the stable
      spatiotemporally periodic solutions in a lattice of diffusively coupled sine
      circle maps with periodic boundary conditions. Spatially periodic initial
      conditions settle down to spatiotemporally periodic solutions over large regions
      of the parameter space. In the case of synchronized solutions resulting from
      synchronized initial conditions, the mode-locked intervals have been seen to
      follow strict Farey ordering in the temporal periods. However, the nature of the
      organization of the mode-locked intervals corresponding to higher spatiotemporal
      periods is highly dependent on initial conditions and on system parameters. Farey
      ordering in the temporal periods is seen at low coupling for mode-locked
      intervals of all spatial periods. On the other hand, stable spatial period two
      solutions show an interesting reversal of Farey ordering at high values of
      coupling. Other spatially periodic solutions show a complete departure from Farey
      ordering at high coupling. We also examine the issue of completeness of the mode
      locked intervals via a calculation of the fractal dimension of the complement of
      the mode-locked intervals as a function of the coupling epsilon and the
      nonlinearity parameter K. Our results are consistent with completeness over a
      range of values for these parameters. Spatiotemporally periodic solutions of the
      traveling wave type have their own organization in the parameter space. Novel
      bifurcations to other types of solutions are seen in the mode-locked intervals.
      We discuss various features of these bifurcations. We also define a set of new
      variables using which an analytic treatment of the bifurcations along the Omega=0
      line is carried out.

PMID- 12005997
TI  - Bifurcations of a semiclassical atom in a periodic field.
AB  - The dynamics of an electron moving in the Coulomb field of a nucleus and a strong
      periodic field is studied in a semiclassical model. Hamiltonian equations of
      motion are derived using Gaussian wave functions, a variational principle, and an
      adiabatic approximation for the width of the wave packets. Predictions for the
      ionization probability are found to agree rather well with exact calculations in
      the barrier suppression regime. By introducing dissipation and fluctuation the
      model atom is considered as an open system. For the dissipative system we
      investigate the bifurcations in dependence on strength and frequency of the
      external field. A quite complex bifurcation scenario is obtained. The sensitivity
      with respect to noise is also studied.

PMID- 12005998
TI  - Fundamental scaling laws of on-off intermittency in a stochastically driven
      dissipative pattern-forming system.
AB  - Noise-driven electroconvection in sandwich cells of nematic liquid crystals
      exhibits on-off intermittent behavior at the onset of the instability. We study
      laser scattering of convection rolls to characterize the wavelengths and
      trajectories of the stochastic amplitudes of the intermittent structures. The
      pattern wavelengths and statistics of these trajectories are in quantitative
      agreement with simulations of the linearized electrohydrodynamic equations. The
      fundamental tau(-3/2) distribution law for the durations tau of laminar phases as
      well as the power law of the amplitude distribution of intermittent bursts are
      confirmed in the experiments. Power spectral densities of the experimental and
      numerically simulated trajectories are discussed.

PMID- 12005999
TI  - Spatial control of a classical electron state in a Rydberg atom by adiabatic
      synchronization.
AB  - An adiabatic synchronization approach is used to control orbital eccentricity and
      inclination of a highly excited electron in a hydrogen atom. The approach is
      based on persisting nonlinear phase locking (autoresonance) between spatially
      uniform, chirped frequency oscillating electric field, and the classical
      Keplerian motion of the electron in the atom. Efficient control in three
      dimensions is achieved by slow passage through and capture into different
      resonances. Scenarios guaranteeing the capture and continuing synchronization in
      the system are outlined, all requiring the driving field amplitude to exceed a
      threshold. The threshold scales as A(3/4), where A is the sweep rate of the
      driving frequency at resonance. The adiabatic synchronization allows one to
      accelerate the electron gradually by using dipolar fields, until approaching the
      stochastic ionization limit.

PMID- 12006000
TI  - Generic two-variable model of excitability.
AB  - We present a simple model that displays all classes of two-dimensional excitable
      regimes. One of the variables of the model displays the usual spikes observed in
      excitable systems. Since the model is written in terms of a "standard" vector
      field, it is always possible to fit it to experimental data displaying spikes in
      an algorithmic way. In fact, we use it to fit a series of membrane potential
      recordings obtained in the medicinal leech and time series generated with the
      FitzHugh-Nagumo equations and the excitability model of Eguia et al. [Phys. Rev.
      E 58, 2636 (1998)]. In each case, we determine the excitability class of the
      corresponding system.

PMID- 12006001
TI  - Multirhythmicity generated by slow variable diffusion in a ring of relaxation
      oscillators and noise-induced abnormal interspike variability.
AB  - The deterministic and noise-dependent dynamics of a ring of three Ohmically
      coupled electronic relaxation oscillators are considered by means of numerical
      simulations. Each isolated oscillator is described by a set of two ordinary
      differential equations with very different characteristic times. The emergence of
      the limit cycle via the Hopf bifurcation results from the N-shaped current-versus
      voltage characteristic of the nonlinear resistor. The phase diagram is calculated
      for a ring of three such oscillators in the presence of small detuning. Special
      attention is focused on two parameter areas, one near a transition to the
      homogeneous and the other near the inhomogeneous stable steady state. Along with
      other nontrivial limit cycles, essentially asymmetrical limit cycles termed
      dynamic traps may arise in these two areas. A dynamic trap is a regime in which
      one or two oscillators do not perform full-amplitude oscillations and,
      correspondingly, do not generate spikes. The interspike interval (ISI)
      distribution in the presence of noise is calculated as a function of the coupling
      strength in both areas of the parameter plane. The distributions are extremely
      polymodal near the homogeneous steady state even if the in-phase limit cycle is
      dominating. The origins of this abnormal enhancement of ISI variability are
      discussed in detail. A similar analysis shows that nontrivial periodic attractors
      are observable in the vicinity of the inhomogeneous stable steady states only if
      the level of noise is relatively low. In this case, the dominance of the in-phase
      limit cycle basin results in an almost unimodal distribution of interspike
      intervals.

PMID- 12006002
TI  - Slow time evolution of two-time-scale reaction-diffusion systems: the physical
      origin of nondiffusive transport.
AB  - We study, from a mesoscopic point of view, the slow time-scale dynamics of a
      mixture of chemicals in which there is a chemical reaction that occurs much
      faster than all other processes, including diffusion. For a simple paradigmatic
      model reaction, it is possible to find a reduced set of dynamical equations
      analytically. This procedure, which yields the same mean field equations as the
      macroscopic approach described by Strier and Dawson [J. Chem. Phys, 112, 825
      (2000)], clarifies the physical origin of some of the terms that appear in the
      reduced reaction-diffusion equations, such as "negative density dependent cross
      diffusion terms," whose actual meaning is hard to assess within the macroscopic
      framework. We also present a two-time-scale reactive lattice gas automaton with
      which it is possible to check the validity of the analytical results and the
      conditions under which the reduced description holds. Using this lattice gas we
      also show how the differential interaction with immobile species can give rise to
      the formation of stable Turing patterns in a system where all the other chemicals
      diffuse approximately at the same rate.

PMID- 12006003
TI  - Deriving exact energy solutions to the symmetrized q-difference Harper equation.
AB  - This paper deals with the application of the q calculus to second order q
      difference equations, like the q symmetrized form of the Harper equation. One
      obtains three-term recurrence relations, for which a symmetrized version is
      written down. This opens the way to establish explicit energy results that are
      dependent on the commensurability parameter. The continuous realization of such
      energy results exhibits interesting patterns characterized by hierarchical
      structures.

PMID- 12006004
TI  - Scroll waves in isotropic excitable media: linear instabilities, bifurcations,
      and restabilized states.
AB  - Scroll waves are three-dimensional analogs of spiral waves. The linear stability
      spectrum of untwisted and twisted scroll waves is computed for a two-variable
      reaction-diffusion model of an excitable medium. Different bands of modes are
      seen to be unstable in different regions of parameter space. The corresponding
      bifurcations and bifurcated states are characterized by performing direct
      numerical simulations. In addition, computations of the adjoint linear stability
      operator eigenmodes are also performed and serve to obtain a number of matrix
      elements characterizing the long-wavelength deformations of scroll waves.

PMID- 12006005
TI  - Dynamical localization in quasiperiodic driven systems.
AB  - We investigate how the time dependence of the Hamiltonian determines the
      occurrence of dynamical localization (DL) in driven quantum systems with two
      incommensurate frequencies. If both frequencies are associated to impulsive
      terms, DL is permanently destroyed. In this case, we show that the evolution is
      similar to a decoherent case. On the other hand, if both frequencies are
      associated to smooth driving functions, DL persists although on a time scale
      longer than in the periodic case. When the driving function consists of a series
      of pulses of duration sigma, we show that the localization time increases as
      sigma(-2) as the impulsive limit, sigma-->0, is approached. In the intermediate
      case, in which only one of the frequencies is associated to an impulsive term in
      the Hamiltonian, a transition from a localized to a delocalized dynamics takes
      place at a certain critical value of the strength parameter. We provide an
      estimate for this critical value, based on analytical considerations. We show
      how, in all cases, the frequency spectrum of the dynamical response can be used
      to understand the global features of the motion. All results are numerically
      checked.

PMID- 12006006
TI  - Delayed self-synchronization in homoclinic chaos.
AB  - The chaotic spike train of a homoclinic dynamical system is self-synchronized by
      applying a time-delayed correction proportional to the laser output intensity.
      Due to the sensitive nature of the homoclinic chaos to external perturbations,
      stabilization of very long-periodic orbits is possible. On these orbits, the
      dynamics appears chaotic over a finite time, but then it repeats with a
      recurrence time that is slightly longer than the delay time. The effect, called
      delayed self-synchronization, displays analogies with neurodynamic events that
      occur in the buildup of long-term memories.

PMID- 12006007
TI  - Probabilistic formalism and hierarchy of models for polydispersed turbulent two
      phase flows.
AB  - This paper deals with a probabilistic approach to polydispersed turbulent two
      phase flows following the suggestions of Pozorski and Minier [Phys. Rev. E 59,
      855 (1999)]. A general probabilistic formalism is presented in the form of a two
      point Lagrangian PDF (probability density function). A new feature of the present
      approach is that both phases, the fluid as well as the particles, are included in
      the PDF description. It is demonstrated how the formalism can be used to show
      that there exists a hierarchy between the classical approaches such as the
      Eulerian and Lagrangian methods. It is also shown that the Eulerian and
      Lagrangian models can be obtained in a systematic way from the PDF formalism.
      Connections with previous papers are discussed.

PMID- 12006008
TI  - Oscillation mode conversion and energy confinement of acoustically agitated
      bubbles.
AB  - The acoustically agitated bubble oscillation in liquids that is considered to be
      related to the half-subharmonic acoustic bubble oscillations is discussed in
      terms of parametric decay instability. At the frequency of about 40 kHz, the half
      subharmonic bubble oscillation mode should be a surface bubble oscillation that
      does not easily emit acoustic waves into water and confines acoustic energy from
      longitudinal waves. The half-subharmonic bubble oscillation is the dominant mode
      that leads to parametric decay instability of bubble oscillations.

PMID- 12006009
TI  - River meandering dynamics.
AB  - The Ikeda, Parker, and Sawai river meandering model is reexamined using a
      physical approach employing an explicit equation of motion. For periodic river
      shapes as seen from above, a cross-stream surface elevation gradient creates a
      velocity shear that is responsible for the decay of small-wavelength meander
      bends, whereas secondary currents in the plane perpendicular to the downstream
      direction are responsible for the growth of large-wavelength bends. A decay
      length D=H/2C(f) involving the river depth H and the friction coefficient C(f)
      sets the scale for meandering, giving the downstream distance required for the
      fluid velocity profile to recover from changes in the channel curvature. Using
      this length scale and a time scale T, we explicitly trace the observed length
      scale invariance to the equations of motion, and predict similar time and
      velocity scale invariances. A general time-dependent nonlinear modal analysis for
      periodic rivers reveals that modes higher than the third mode are needed to
      describe upstream migration of bend apexes just before oxbow cutoff, and are
      important to accurate calculations of the time and sinuosity at cutoff.

PMID- 12006010
TI  - Numerical study of comparison of vorticity and passive vectors in turbulence and
      inviscid flows.
AB  - The nonlinear vortex stretching in incompressible Navier-Stokes turbulence is
      compared with a linear stretching process of passive vectors (PVs). In
      particular, we pay special attention to the difference of these processes under
      long and short time evolutions. For finite time evolution, we confirm our
      previous finding that the stretching effect of vorticity is weaker than that of
      general passive vectors for a majority of the initial conditions with the same
      energy spectra. The above difference can be explained qualitatively by examining
      the Biot-Savart formula. In order to see to what extent infinitesimal time
      development explains the above difference, we examine the probability density
      functions (PDFs) of the stretching rates of the passive vectors in the vicinity
      of a solution of Navier-Stokes equations. It is found that the PDFs are found to
      have a Gaussian distribution, suggesting that there are equally many PVs that
      stretched less and more than the vorticity. This suggests the importance of the
      vorticity-strain correlation built up over finite time in turbulence. We also
      discuss the case of Euler equations, where the dynamics of the Jacobian matrix
      relating the physical and material coordinates is examined numerically. A kind of
      alignment problem associated with the Cauchy-Green tensor is proposed and studied
      using the results of numerical simulations. It is found that vorticity tends to
      align itself with the most compressing eigenvector of the Cauchy-Green tensor. A
      two-dimensional counterpart of active-passive comparison is briefly studied.
      There is no essential difference between stretching of vorticity gradients and
      that of passive scalar gradients and a physical interpretation is given to it.

PMID- 12006011
TI  - Lattice-gas model based on field mediators for immiscible fluids.
AB  - A Boolean lattice-gas model based on field mediators is proposed for simulating
      the flow of immiscible fluids. The field mediators introduced here simulate long
      range action, enabling the use of local rules in separation step and, by avoiding
      the optimization step, reduce computer processing time with respect to previous
      models. In addition, field strength and interaction distance is modeled by
      introducing distinct emission P(e) and extinction P(a) probabilities, for field
      mediators, enabling us to control interfacial tension and transition thickness.
      The model's microdynamics is fully described and macroscopic parameters are
      related to model's parameters after a Chapman-Enskog asymptotic expansion for the
      ensemble-average distributions. Simulation results are presented for several
      sample case studies, including the verification of Laplace's law, coalescence
      phenomenon, interaction of a pair of wetting and nonwetting fluids with solid
      surfaces, and droplet formation under the action of gravity. These results are
      compared with available data.

PMID- 12006012
TI  - Energy-conserving low-order models for three-dimensional Rayleigh-Benard
      convection.
AB  - Constructing hydrodynamic low-order models in the form of coupled gyrostats
      eliminates the possibility of certain unphysical behaviors, such as solutions
      diverging to infinity, that often appear in models resulting from ad hoc
      truncations of Galerkin approximations. In this paper, a simple low-order model
      in a gyrostatic form that conserves energy in the dissipationless limit (Model I)
      is constructed for three-dimensional (3D) Rayleigh-Benard convection. It can be
      considered an energy-conserving extension of the model by Das et al. [Phys. Rev.
      E 62, R3051 (2000)] (Model II) that does not conserve energy and possesses
      solutions diverging to infinity. Also studied here is a smaller but energy
      conserving subsystem of Model I that has the form of two coupled gyrostats (Model
      III). This new system is the 3D analog of the celebrated Lorenz model [J. Atmos.
      Sci. 20, 130 (1963)]. Stability diagrams and heat transport behavior are
      calculated and compared for the three models. Model I has improved qualitative
      agreement with experimental observations compared to that of Model II and Model
      III.

PMID- 12006013
TI  - Scaling hypothesis leading to generalized extended self-similarity in turbulence.
AB  - A scaling hypothesis leading to generalized extended self-similarity (GESS) for
      velocity structure functions, valid for intermediate scales in isotropic,
      homogeneous turbulence, is proposed. By introducing an effective scale r,
      monotonically depending on the physical scale r, with the use of the large
      deviation theory, the asymptotic forms of the probability densities for the
      velocity differences u(r) and for the coarse-grained energy-dissipation rate
      fluctuations epsilon(r), compatible with this GESS, are proposed. The probability
      density for epsilon(r) is shown to have the form P(r)(epsilon) approximately
      equal to epsilon(-1)(r/L)(S(r)[z(r)](epsilon))) with
      z(r)(epsilon)=ln(epsilon/epsilon(L))/ln(L/r), where L and epsilon(L) are the
      stirring scale and the coarse-grained energy-dissipation rate over the scale L.
      The concave function S(r)(z), the spectrum, plays the central role of the present
      approach. Comparing the results with numerical and experimental data, we
      explicitly obtain the fluctuation spectra S(r)(z).

PMID- 12006014
TI  - Discrete lattice effects on the forcing term in the lattice Boltzmann method.
AB  - We show that discrete lattice effects must be considered in the introduction of a
      force into the lattice Boltzmann equation. A representation of the forcing term
      is then proposed. With the representation, the Navier-Stokes equation is derived
      from the lattice Boltzmann equation through the Chapman-Enskog expansion. Several
      other existing force treatments are also examined.

PMID- 12006015
TI  - Light emission of sonoluminescent bubbles containing a rare gas and water vapor.
AB  - We present numerical simulations of sonoluminescent rare-gas bubbles in water,
      which account for (i) time variations of the water vapor content, (ii) chemical
      reactions, and (iii) the ionization of the rare gas and the H2O dissociation
      products. Peak temperatures exceed 10 000 K at densities of a few hundred amagat
      ( approximately 10(28) particles per m(3)). The gas mixture in the bubble is
      weakly ionized. Our model accounts for the light emission by electron-atom,
      electron-ion, and ion-atom bremsstrahlung, recombination radiation, and radiative
      attachment of electrons to hydrogen and oxygen atoms, which are all more or less
      important for single bubble sonoluminescence. Spectral shapes, spectral
      intensities, and durations of the light pulses are computed for helium, argon,
      and xenon bubbles. We generally obtain good agreement with the observations for
      photon numbers and pulse durations. Some calculated spectral profiles agree,
      however, less well with observations, especially in the case of the low water
      temperature and for helium bubbles. We try to identify the reasons why computed
      and observed spectral profiles might discernibly differ when all other computed
      features considered here seem to be quite consistent with observations. We show
      that by allowing the bubble to heat somewhat nonisotropically, agreement between
      observed and computed spectral profiles may be obtained, even in the case of
      helium bubbles at freezing water temperatures. In this case, charge exchange
      radiation and related processes involving helium atoms and ions become important.

PMID- 12006016
TI  - Effect of surfactants, polymers, and alcohol on single bubble dynamics and
      sonoluminescence.
AB  - The radial dynamics of an acoustically driven single bubble, levitated in water,
      along with the sonoluminescence (SL) signal, were recorded in the absence and in
      the presence of micromolar quantities of different surfactants and polymers. It
      was observed that these nonvolatile solutes, in the low concentration range used,
      did not significantly affect the radial dynamics nor the SL intensity of a single
      bubble in water. In contrast, the addition of micromolar quantities of a volatile
      solute, pentanol, quenched approximately 90% of the SL without affecting the
      radial dynamics of the bubble.

PMID- 12006017
TI  - Nonlocal electron kinetics and excited state densities in a magnetron discharge
      in argon.
AB  - The densities of argon metastable (3)P(2), and resonance (1)P(1), (3)P(1) states
      were measured along a cylindrical magnetron discharge radius by absorption
      spectroscopy using a narrow bandwidth single mode diode laser. The theoretical
      treatment includes calculations of the rates of numerous excitation and decay
      processes based on nonlocal electron kinetics, and analysis of the transport
      equations for the resonance and metastable atoms. The solution technique of the
      Biberman-Holstein equation of radiation transport is developed in conformity with
      magnetron discharge geometry. The radial profile of the effective lifetime is
      obtained, taking into account radiation escape on the inner and outer electrodes.
      The distinction in formations of the radial profiles of the resonance and
      metastable atoms caused by specifics of radiation transport and diffusion is
      demonstrated. The results of experiments and calculations are compared.

PMID- 12006018
TI  - Non-neutral plasma column in an asymmetric trapping field.
AB  - A non-neutral plasma column in an asymmetric trapping field is considered in this
      paper. It is shown that nonlinearly interacting bulk plasma oscillations and
      quadrupole surface waves allow an exact analytical description. The absence of
      symmetry leads to nonintegrability and other nonlinear phenomena, such as passage
      through different resonances and phase locking. These phenomena should be
      observable in experiments involving elliptical traps and rotating walls and can
      affect the latters' applications.

PMID- 12006019
TI  - Magnetic field generation through angular momentum exchange between circularly
      polarized radiation and charged particles.
AB  - The interaction between circularly polarized radiation and charged particles can
      lead to generation of magnetic field through an inverse Faraday effect. The spin
      of the circularly polarized electromagnetic wave can be converted into the
      angular momentum of the charged particles so long as there is dissipation. We
      demonstrate this by considering two mechanisms of angular momentum absorption
      relevant for laser-plasma interactions: electron-ion collisions and ionization.
      The precise dissipative mechanism, however, plays a role in determining the
      efficiency of the magnetic-field generation.

PMID- 12006020
TI  - Self-consistent kinetic theory of a plasma sheath.
AB  - A fully kinetic theory model of the sheath of a dc glow discharge is presented.
      This model includes a direct numerical solution of Boltzmann equations for the
      spatial and velocity dependence of the electron and Ar+ distribution functions
      with a self-consistent electric field calculated from the Poisson equation. The
      solution is obtained using a collocation method that employs Legendre quadrature
      points for both angular and spatial variables, and nonclassical speed quadrature
      points for velocity. The results of the steady state direct numerical solution
      are compared with a particle-in-cell Monte Carlo simulation. As anticipated, it
      is found that the space- and energy-dependent ion distribution function varies
      strongly with a decrease in the ratio of the Debye length to the ion mean free
      path.

PMID- 12006021
TI  - Spheromak as a relaxed state with minimum dissipation.
AB  - The principle of minimum dissipation of energy is utilized to obtain the
      spheromak configuration as a relaxed state. The Euler-Lagrange equation for the
      minimum dissipative relaxed state is solved in terms of Chandrasekhar-Kendall
      eigenfunctions analytically generalized in the complex domain. This state is non
      force-free and further shows the nonconstancy of the ratio of parallel current to
      the magnetic field.

PMID- 12006022
TI  - Influence of Ar(2)+ in an argon collisional-radiative model.
AB  - A nonlinear time-dependent collisional-radiative model for recombining argon is
      presented. Reactions involving Ar(2)+ are taken into account and their influence
      is discussed. It is shown that Ar(2)+ may increase the time to reach the quasi
      steady-state by a factor of 100. The calculation of the recombination rate
      coefficient at the quasi-steady-state is presented. An analytical expression is
      derived and compared with existing literature values. The importance of the
      increase of the quasi-steady-state time is illustrated by comparisons of excited
      levels population densities distribution measured in a fast moving plasma where
      the mechanical time scale is sufficiently short to provide a time-dependent
      chemistry in a reference frame moving with the flow. The high sensitivity of the
      results towards the electron number density is pointed out. Finally, the
      influence of the processes involving Ar(2)+ on the excitation temperature is
      discussed.

PMID- 12006023
TI  - Electrical conductivity of nonideal carbon and zinc plasmas: experimental and
      theoretical results.
AB  - Electrical conductivities of nonideal carbon and zinc plasmas have been measured
      in this paper. The plasma is produced by vaporizing a wire placed in a glass
      capillary within some hundred nanoseconds. In the case of carbon, vaporization
      occurs with good reproducibility when utilizing a preheating system. The particle
      density is in the range of n=(1-10) x 10(21) cm(-3). The plasma temperature,
      which is obtained by fitting a Planck function to the measured spectrum, is
      between 7-15 kK. Plasma radius and behavior of the plasma expansion were studied
      with a streak, a framing or an intensified charge coupled device camera. We
      compare the measured electrical conductivities with theoretical results, which
      were obtained solving quantum kinetic equations for the nonideal partially
      ionized plasmas. In this approach, the transport cross sections are calculated on
      the level of a T-matrix approximation using effective potentials. The plasma
      composition is determined from a system of coupled mass action laws with
      nonideality corrections.

PMID- 12006024
TI  - Three-dimensional particle-in-cell simulations of energetic electron generation
      and transport with relativistic laser pulses in overdense plasmas.
AB  - The interaction of relativistic laser light with overdense plasmas is studied by
      three-dimensional particle-in-cell simulations. Generation of layered current
      sheets and quasistatic magnetic fields is observed near the target surface owing
      to anisotropic laser filamentation and Weibel instabilities. Later these current
      sheets tear into filaments that partially merge with each other to form isolated
      magnetic channels penetrating into the dense plasmas. It is found that fast
      electron energy flow is not only inside the magnetic channels but also it is
      widely distributed outside the channels. This is possible because of electron
      anomalous diffusion across self-generated magnetic fields. Consequently, the
      total hot electron current exceeds a few hundred kiloamperes and is much larger
      than the Alfven current. Hence a considerable amount of energy flows towards the
      plasma core. Significant heating of the bulk plasma electrons is also observed.

PMID- 12006025
TI  - Plasma instability of a vacuum arc centrifuge.
AB  - Ever since conception of the vacuum arc centrifuge in 1980, periodic fluctuations
      in the ion saturation current and floating potential have been observed in
      Langmuir probe measurements in the rotation region of a vacuum arc centrifuge. In
      this work we develop a linearized theoretical model to describe a range of
      instabilities in the vacuum arc centrifuge plasma column, and then test the
      validity of the description through comparison with experiment. We conclude that
      the observed instability is a "universal" instability, driven by the density
      gradient, in a plasma with finite conductivity.

PMID- 12006026
TI  - Electron cooling of high-energy protons in a multiring trap with a tank circuit
      monitoring the electron-plasma oscillations.
AB  - Electron cooling of energetic protons in a multiring trap was investigated
      experimentally with a tank circuit monitoring electron-plasma oscillations in the
      trap. The energy of protons was determined by time-of-flight measurements. It is
      found that a simple model can explain the qualitative behavior of both electron
      and proton energy when the initial energy of protons is less than 2 keV.
      Monitoring the electron-plasma temperature with a tank circuit can be an
      effective tool when energetic particles are electron cooled in a multiring trap.

PMID- 12006027
TI  - Analysis of Thomson scattered light from an arc plasma jet.
AB  - In this paper we present an analysis of Thomson scattered light from an arc
      plasma jet. Our approach goes beyond the standard random-phase approximation
      (RPA) and provides more consistent data for the electron temperature and density
      in plasmas that are weakly nonideal and collisional. The theory is based on a
      memory function formalism for the spectral density function with the use of the
      three lowest-order frequency-moment sum rules. These moments are then corrected
      for temperature inhomogeneities in the scattering volume. The proposed
      interpretation of scattering data is compared with the RPA result and with the
      standard Bhatnagar-Gross-Krook collisional model for the dynamic structure
      factor. It is shown that the obtained electron temperature values are closer but
      not equal to local thermodynamic equilibrium temperature values extracted from
      spectroscopic measurements.

PMID- 12006028
TI  - Time-resolved ion flux measurements in pulsed, electron-beam-generated plasmas.
AB  - Time-resolved ion flux and energy distributions were measured at an electrode
      located adjacent to pulsed, electron-beam-generated plasmas in argon and oxygen.
      Temporal variations in the incident Ar+, O+, and O(2)+ energy and flux were
      correlated to changes in the electron temperature and plasma density. The decay
      time of the oxygen plasma is found to be shorter than that of the argon plasma,
      which is understood by considering the different loss mechanisms of each ion
      species.

PMID- 12006029
TI  - Rotational kinetics of absorbing dust grains in neutral gas.
AB  - We study the rotational and translational kinetics of massive particulates (dust
      grains) absorbing the ambient gas. Equations for microscopic phase densities are
      deduced resulting in the Fokker-Planck equation for the dust component. It is
      shown that although there is no stationary distribution, the translational and
      rotational temperatures of dust tend to certain values, which differ from the
      temperature of the ambient gas. The influence of the inner structure of grains on
      rotational kinetics is also discussed.

PMID- 12006030
TI  - Possibility of an unequivocal test of different models of the equation of state
      of aluminum in the coupling regime Gamma approximately 1-50.
AB  - The equation of state (EOS) in regimes of density (rho) and temperature (T) which
      are inaccessible to experiment has to be determined using theories which may
      themselves be out of their range of validity. Even for Al, the EOS in the region
      0.1<rho<2 g cm(-3), and 1<T<50 eV, where the ionic coupling parameter Gamma
      ranges from 1- approximately 50, is not unknown. We present results for the EOS
      using the Thomas-Fermi model (TF), the quotidian equation of state, the Sesame
      tabulation, and using the density-functional neutral-pseudoatom (NPA) model which
      is a first-principles theory applicable at strong coupling. It is found that the
      NPA predictions are very different from the other models, and experiments could
      provide an unequivocal test of the validity of the different EOS models. We
      report theoretical results for the Hugoniot, and the electrical conductivity in
      the regime of interest.

PMID- 12006031
TI  - Dynamics of self-trapped singular beams in an underdense plasma.
AB  - Dynamics of an intense short laser pulse with a phase singularity, propagating in
      an underdense cold plasma, is investigated. Such a pulse can propagate as a
      vortex soliton in a self-created channel. It is shown that vortices with the
      topological charge m=1,2 (and a corresponding angular momentum) are unstable
      against symmetry-breaking perturbations; the breakup of the original vortex leads
      to the formation of stable spatial solitons that steadily fly away tangentially
      from the initial ring of vortex distribution.

PMID- 12006032
TI  - Stability of particle arrangements in a complex plasma.
AB  - It is shown that the stability of the vertical and horizontal confinement of
      colloidal "dust" particles levitating in a complex plasma appears as a nontrivial
      interplay of the external confining forces as well as the interparticle
      interactions and plasma collective processes such as the wake formation.

PMID- 12006033
TI  - Statistical effects in the multistream model for quantum plasmas.
AB  - A statistical multistream description of quantum plasmas is formulated, using the
      Wigner-Poisson system as dynamical equations. A linear stability analysis of this
      system is carried out, and it is shown that a Landau-like damping of plane wave
      perturbations occurs due to the broadening of the background Wigner function that
      arises as a consequence of statistical variations of the wave function phase. The
      Landau-like damping is shown to suppress instabilities of the one- and two-stream
      type.

PMID- 12006034
TI  - X-ray emission of a xenon gas jet plasma diagnosed with Thomson scattering.
AB  - We present the results of a benchmark experiment aimed at validating recent
      calculation techniques for the emission properties of medium and high-Z
      multicharged ions in hot plasmas. We use space- and time-resolved M-shell x-ray
      spectroscopy of a laser-produced gas jet xenon plasma as a primary diagnostic of
      the ionization balance dynamics. We perform measurements of the electron
      temperature, electron density, and average charge state by recording simultaneous
      spectra of ion acoustic and electron plasma wave Thomson scattering. A comparison
      of the experimental x-ray spectra with calculations performed ab initio with a
      non-local-thermodynamic-equilibrium collisional-radiative model based on the
      superconfiguration formalism, using the measured plasma parameters, is presented
      and discussed.

PMID- 12006035
TI  - Parameters and equilibrium profiles for large-area surface-wave sustained
      plasmas.
AB  - The equilibrium profiles of the plasma parameters of large-area rf discharges in
      a finite-length metal-shielded dielectric cylinder are computed using a two
      dimensional fluid code. The rf power is coupled to the plasma through edge
      localized surface waves traveling in the azimuthal direction along the plasma
      edge. It is shown that self-consistent accounting for axial plasma diffusion and
      radial nonuniformity of the electron temperature can explain the frequently
      reported deviations of experimentally measured radial density profiles from that
      of the conventional linear diffusion models. The simulation results are in a good
      agreement with existing experimental data obtained from surface-wave sustained
      large-diameter plasmas.

PMID- 12006036
TI  - Nonlinear electrostatic emittance compensation in kA, fs electron bunches.
AB  - Nonlinear space-charge effects play an important role in emittance growth in the
      production of kA electron bunches with a bunch length much smaller than the bunch
      diameter. We propose a scheme employing the radial third-order component of an
      electrostatic acceleration field, to fully compensate the nonlinear space-charge
      effects. This results in minimal transverse root-mean-square emittance. The
      principle is demonstrated using our design simulations of a device for the
      production of high-quality, high-current, subpicosecond electron bunches using
      electrostatic acceleration in a 1 GV/m field. Simulations using the GPT code
      produce a bunch of 100 pC and 73 fs full width at half maximum pulse width,
      resulting in a peak current of about 1.2 kA at an energy of 2 MeV. The
      compensation scheme reduces the root-mean-square emittance by 34% to 0.4pi mm
      mrad.

PMID- 12006037
TI  - Acceleration element for femtosecond electron pulse compression.
AB  - An acceleration element is proposed for compressing the electron pulse duration
      in a femtosecond photoelectron gun. The element is a compact metal cavity with
      curved-shaped walls. An external voltage is applied to the cavity where a special
      electric field forms in such a way that the slow electrons in the electron pulse
      front are accelerated more than the fast electrons, and consequently the electron
      pulse duration will be compressed. The distribution of the electric field inside
      the acceleration cavity is analyzed for the geometry of the cavity. The electron
      dynamics in this acceleration cavity is also investigated numerically. Numerical
      results show that the electron pulse front and pulse duration can be improved by
      compensating for the effects of space charge and the initial energy spread of
      photoelectrons with a Lambertian angular distribution. Depending on the design
      parameters and the shape of the electron pulse, for a femtosecond electron gun
      with an electron energy of 30 keV, 10(3) electrons per pulse, and an electron
      drift length of 40 cm, the electron pulse duration can be reduced from 550 to 200
      fs when using a compensating cavity with an average radius of 1.7 and 5.6 cm in
      length. Electron pulses shorter than 200 fs can be achieved if the length of the
      drift region is reduced.

PMID- 12006038
TI  - Self-amplified coherent spontaneous emission in the planar wiggler free-electron
      laser.
AB  - Coherent spontaneous emission (CSE) is a potentially important self-generated
      source of seed radiation in a free-electron laser (FEL) amplifier. A model is
      derived that describes CSE at the fundamental resonant frequency and its
      harmonics in a planar wiggler FEL. The subsequent self-amplification of the CSE
      is investigated in the nonlinear regime for a FEL amplifier configuration.

PMID- 12006039
TI  - Trapping, compression, and acceleration of an electron bunch in the nonlinear
      laser wakefield.
AB  - A scheme of laser wakefield acceleration, when a relatively rare and long bunch
      of nonrelativistic or weakly relativistic electrons is initially in front of the
      laser pulse, is suggested and considered. The motion of test electrons is studied
      both in the one-dimensional (1D) case (1D wakefield) and in the case of three
      dimensional laser wakefield excited in a plasma channel. It is shown that for
      definite parameters of the problem the bunch can be trapped, effectively
      compressed both in longitudinal and transverse directions, and accelerated to
      ultra-relativistic energies in the region of first accelerating maximum of the
      wakefield. The accelerated bunch has sizes much less than the plasma wavelength
      and relatively small energy spread.

PMID- 12006040
TI  - Nonlinear quantum regime of the x-ray Compton laser.
AB  - In this work a scheme of x-ray coherent radiation generation in the nonlinear
      quantum regime by means of mildly relativistic high density electron beams and a
      strong pump laser field is investigated. The consideration is based on a self
      consistent set of Maxwell and relativistic quantum kinetic equations. The coupled
      equations are solved in the slowly varying envelope approximation.

PMID- 12006041
TI  - Canonical Hamiltonian formulation of the nonlinear Schrodinger equation in a one
      dimensional, periodic Kerr medium.
AB  - A canonical Hamiltonian formulation of the nonlinear Schrodinger equation has
      been derived in this paper. This formulation governs the dynamics of pulse
      propagation in a one-dimensional, periodic Kerr medium when the frequency content
      of the pulse is sufficiently narrow relative to a carrier frequency, and
      sufficiently far removed from a photonic band gap of the medium. Our Hamiltonian
      is numerically equal to the energy, and our fields obey canonical commutation
      relations, so the theory can easily be quantized. We clarify the nature of the
      conserved quantities associated with simple symmetries.

PMID- 12006042
TI  - Transition between ground state and metastable states in classical two
      dimensional atoms.
AB  - Structural and static properties of a classical two-dimensional system consisting
      of a finite number of charged particles that are laterally confined by a
      parabolic potential are investigated by Monte Carlo simulations and the Newton
      optimization technique. This system is the classical analog of the well-known
      quantum dot problem. The energies and configurations of the ground and all
      metastable states are obtained. In order to investigate the barriers and the
      transitions between the ground and all metastable states we first locate the
      saddle points between them, then by walking downhill from the saddle point to the
      different minima, we find the path in configurational space from the ground state
      to the metastable states, from which the geometric properties of the energy
      landscape are obtained. The sensitivity of the ground-state configuration on the
      functional form of the interparticle interaction and on the confinement potential
      is also investigated.

PMID- 12006043
TI  - Speckle experiments in random lasers.
AB  - We present measurements of speckle in a random laser. We analyze its first-order
      statistics and show that, contrary to what might be expected for passive systems,
      analyses of the intensity distribution P(I) and the speckle spot size do provide
      information about light transport inside the system. P(I) is used to determine
      the degree to which an incident probe is amplified by the random laser. The
      shrinking speckle spot size reflects the change in path length distribution
      P(Lambda); we deduce that the average path length <Lambda> in the studied random
      laser is two times longer above threshold than in a passive diffusive system.

PMID- 12006044
TI  - Orientational discrete breathers in hydrogen-bonded chains.
AB  - We consider rotational motion of protons within a hydrogen-bonded zig-zag chain.
      Each proton is subjected to a Coulomb interaction from the three nearest heavy
      ions, as well as from the two neighboring protons. The hydrogen bonding is
      modeled with an additional double-minimum on-site potential. The system admits
      discrete breather solutions in the gap below the phonon band. The numerically
      exact procedure using an anticontinuum limit is exploited to obtain these
      solutions, which appear to be asymmetric due to the asymmetry of the interaction
      potential. Only single-well orbits are considered. A linear stability analysis is
      performed. The discrete breather solutions are shown to be linearly stable
      provided the nonresonance condition is satisfied, and they turn out to be
      unstable in the region of 2:3 parametric resonance. Phonon-breather solutions are
      found in the 1:2 resonance region. Two kinds of two-site breather solutions are
      investigated.

PMID- 12006045
TI  - Classical versus quantum structure of the scattering probability matrix: chaotic
      waveguides.
AB  - The purely classical counterpart of the scattering probability matrix
      (SPM)/S(n,m)/(2) of the quantum scattering matrix S is defined for two
      dimensional quantum waveguides for an arbitrary number of propagating modes M. We
      compare the quantum and classical structures of /S(n,m)/(2) for a waveguide with
      generic Hamiltonian chaos. It is shown that even for a moderate number of
      channels, knowledge of the classical structure of the SPM allows us to predict
      the global structure of the quantum one and, hence, understand important quantum
      transport properties of waveguides in terms of purely classical dynamics. It is
      also shown that the SPM, being an intensity measure, can give additional
      dynamical information to that obtained by the Poincare maps.

PMID- 12006046
TI  - Two-dimensional clusters of solitary structures in driven optical cavities.
AB  - Using analytical and numerical approaches we study clusters of the two
      dimensional localized structures of light excited in the externally driven
      optical cavities. Stability and instability properties of clusters of two, three,
      and four structures are analyzed in detail. We develop a technique for
      calculation of the expression for the interaction potential through modified
      Bessel functions that has applicability going beyond the model under
      consideration. Qualitative differences between stability properties of triangular
      and square structures are found that emphasize the role of diagonal interactions
      in the latter.

PMID- 12006047
TI  - Superluminal pulse propagation through one-dimensional photonic crystals with a
      dispersive defect.
AB  - The propagation of a pulse through one-dimensional photonic crystals that contain
      a dispersive and absorptive defect layer doped with two-level atoms is discussed.
      The dynamical evolution of the pulse inside the photonic crystal is presented.
      Superluminal negative group velocity (the peak appears at the exit end before it
      reaches the input end) is discovered. Although the group velocity is larger than
      c and even negative, the velocity of energy propagation never exceeds the vacuum
      light speed. The appearance of the superluminal advance or subluminal delay of
      the pulse peak inside the photonic crystal or at the exit end is due to the wave
      interference from Bragg reflections.

PMID- 12006048
TI  - Self-interference between forward and backward propagating parts of a single
      acoustic plate mode.
AB  - Near and far fields of a particular (S(1)) Lamb mode, generated on a steel plate
      by means of a wedge transducer, are investigated. These show an oscillating
      behavior of the radial profile of the acoustic field amplitude that can be
      interpreted and modelled as interference phenomenon between forward and backward
      propagating parts of the Lamb mode, simultaneously generated at the interface
      between transducer and plate.

PMID- 12006049
TI  - Exact calculation of the angular momentum loss, recoil force, and radiation
      intensity for an arbitrary source in terms of electric, magnetic, and toroid
      multipoles.
AB  - An exact calculation of the radiation intensity, angular momentum loss, and the
      recoil force for the most general type of source, characterized by electric,
      magnetic, and toroid multipole moments and radii of any multipolarity and an
      arbitrary time dependence, is presented. The results are expressed in terms of
      time derivatives of the multipole moments and mean radii of the corresponding
      distributions. Although quite cumbersome, the formulas found by us represent
      exact results in the correct multipole analysis of configurations of charges and
      currents that contain toroidal sources. So the longstanding problem in classical
      electrodynamics of relating the radiation properties of a system to quantities
      completely describing its internal electromagnetic structure is thereby exactly
      solved. By particularizations to the first multipole contributions, corrections
      to the familiar formulas from books are found, mostly on account of the toroid
      moments and their interference with the usual electric and magnetic ones.

PMID- 12006050
TI  - Measurement of superluminal optical tunneling times in double-barrier photonic
      band gaps.
AB  - Tunneling of optical pulses at 1.5 microm wavelength through double-barrier
      periodic fiber Bragg gratings is experimentally investigated in this paper.
      Tunneling time measurements as a function of the barrier distance show that, far
      from resonances of the structure, the transit time is paradoxically short-
      implying superluminal propagation--and almost independent of the barrier
      distance. This result is in agreement with theoretical predictions based on phase
      time analysis and provides, in the optical context, an experimental evidence of
      the analogous phenomenon in quantum mechanics of nonresonant superluminal
      tunneling of particles across two successive potential barriers.

PMID- 12006051
TI  - Diffraction by a small aperture in conical geometry: application to metal-coated
      tips used in near-field scanning optical microscopy.
AB  - Light diffraction through a subwavelength aperture located at the apex of a
      metallic screen with conical geometry is investigated theoretically. A method
      based on a multipole field expansion is developed to solve Maxwell's equations
      analytically using boundary conditions adapted both for the conical geometry and
      for the finite conductivity of a real metal. The topological properties of the
      diffracted field are discussed in detail and compared to those of the field
      diffracted through a small aperture in a flat screen, i.e., the Bethe problem.
      The model is applied to coated, conically tapered optical fiber tips that are
      used in near-field scanning optical microscopy. It is demonstrated that such tips
      behave over a large portion of space like a simple combination of two effective
      dipoles located in the apex plane (an electric dipole and a magnetic dipole
      parallel to the incident fields at the apex) whose exact expressions are
      determined. However, the large "backward" emission in the P plane--a salient
      experimental fact that has remained unexplained so far--is recovered in our
      analysis, which goes beyond the two-dipole approximation.

PMID- 12006052
TI  - Local optical density of states in finite crystals of plane scatterers.
AB  - Spontaneous emission rates in a dielectric structure are position dependent and
      proportional to the local optical density of states. The latter can be calculated
      when the Green function is known. In our scalar formalism, we model dielectric
      slabs as infinitely thin planes and use the T-matrix formalism of multiple
      scattering theory to find an exact analytical expression for the Green function
      of a dielectric mirror of arbitrary number of unit cells N. All the propagating
      and guided modes of the structure are found. There are at most N guided modes and
      their dispersion relations are studied. The guided modes appear around
      frequencies corresponding to the first stop band in normal direction. Local
      densities of propagating and guided modes are presented, also for frequencies
      where the layered structure acts as an omnidirectional mirror.

PMID- 12006053
TI  - Continuum approach to discreteness.
AB  - We study analytically and numerically continuum models derived on the basis of
      Pade approximations and their effectiveness in modeling spatially discrete
      systems. We not only analyze features of the temporal dynamics that can be
      captured through these continuum approaches (e.g., shape oscillations, radiation
      effects, and trapping) but also point out ones that cannot be captured (such as
      Peierls-Nabarro barriers and Bloch oscillations). We analyze the role of such
      methods in providing an effective "homogenization" of spatially discrete, as well
      as of heterogeneous continuum equations. Finally, we develop numerical methods
      for solving such equations and use them to establish the range of validity of
      these continuum approximations, as well as to compare them with other
      semicontinuum approximations.

PMID- 12006054
TI  - Interaction of N solitons in the massive Thirring model and optical gap system:
      the complex Toda chain model.
AB  - Using the Karpman-Solov'ev quasiparticle approach for soliton-soliton interaction
      we show that the train propagation of N well-separated solitons of the massive
      Thirring model is described by the complex Toda chain with N nodes. For the
      optical gap system a generalized (nonintegrable) complex Toda chain is derived
      for description of the train propagation of well-separated gap solitons. These
      results are in favor of the recently proposed conjecture of universality of the
      complex Toda chain.

PMID- 12006055
TI  - X-ray diffraction study of Anodisc filters.
AB  - X-ray diffraction from Anodisc membrane filters is measured and analyzed. The
      patterns are consistent with pores of constant diameter and a Gaussian
      distribution of pore-pore spacing. The mean distance between pores, measured
      using x rays is 0.37 microm compared to 0.32 microm calculated from the nominal
      density of pores/cm(2). The results may be modeled both in terms of the
      convolution of a structure factor of the pores with the resolution function, and
      by modeling the source as a collection of incoherent sources with an ideal
      monochromator crystal. The incoherent source analysis provides an explanation for
      the common observation that the resolution function in many x-ray spectrometers
      is better fit to a sum of Lorentzians, rather than a single Lorentzian.

PMID- 12006056
TI  - Magnetic-field-induced control of breather dynamics in a single plaquette of
      Josephson junctions.
AB  - We present a theoretical study of inhomogeneous dynamic (resistive) states in a
      single plaquette consisting of three Josephson junctions. Resonant interactions
      of such a breather state with electromagnetic oscillations manifest themselves by
      resonant current steps and voltage jumps in the current-voltage characteristics.
      An externally applied magnetic field leads to a variation of the relative shift
      between the Josephson current oscillations of two resistive junctions. By making
      use of the rotation wave approximation analysis and direct numerical simulations
      we show that this effect allows to effectively control the breather
      instabilities, e.g., to increase (decrease) the height of the resonant steps and
      to suppress the voltage jumps in the current-voltage characteristics.

PMID- 12006057
TI  - Two-frequency mutual coherence function and pulse propagation in random media.
AB  - In this work an analysis of transient wave propagation in forward scattering
      random media is presented. The analysis is based on evaluation of the two
      frequency mutual coherence function, which is an important quantity in itself
      since it provides a measure of the coherence bandwidth. The coherence function is
      calculated by using the path integral technique; specifically, by resorting to a
      cumulant expansion of the path integral. In contrast to the formulas available in
      the literature, the solution obtained is not limited by the strength of disorder
      and applies equally well to both dispersive and nondispersive media, with
      arbitrary spectra of inhomogeneities. For the regime of weak scattering (or
      relatively short propagation distances) the first cumulant gives an excellent
      approximation coinciding with the results obtained earlier in a particular case
      of the Kolmogorov turbulence by solving the corresponding differential equation
      numerically. In the regime of strong scattering (long distances), which to our
      knowledge has not been covered previously, our solution demonstrates a different
      type of scaling dependence. It is shown that, even for power spectra with fractal
      behavior in a wide range of spatial frequencies, the coherence function is very
      sensitive to fine details of the spectrum at both small and large spatial scales.
      Using the cumulant expansion, the temporal moments of the pulsed wave propagating
      in a random medium are also considered. It is found that the temporal moments of
      the pulse are determined exactly by accounting for a corresponding number of the
      cumulants. In particular, the average time delay of the pulse is determined by
      the first cumulant, and the pulse width is obtained by accounting for the first
      two cumulants. Although the consideration of the problem is based on the model of
      a continuous medium, the results are also applicable to wave propagation in media
      containing discrete particles scattering predominantly in the forward direction.

PMID- 12006058
TI  - Self-interaction near dielectrics.
AB  - We compute the force acting on a free, static electric charge outside a uniform
      dielectric sphere. We view this force as a self-interaction force, and compute it
      by applying the Lorentz force directly to the charge's electric field at its
      location. We regularize the divergent bare force using two different methods: A
      direct application of the Quinn-Wald comparison axiom and mode-sum
      regularization.

PMID- 12006059
TI  - Exact discrete compactlike traveling kinks and pulses in phi(4) nonlinear
      lattices.
AB  - We show that by properly choosing the analytical form of a solitary wave solution
      of discrete phi(4) models we can calculate the parameters of the potential which
      allow the propagation of compact (kink and pulses) solutions. Our numerical
      simulations show that narrow kinks and pulses with finite extent can propagate
      freely, and that discrete breathers with finite but long lifetime, can emerge
      from their collisions. Moreover, our numerical simulations reveal that the
      propagation of two successive pulses at a relative distance of two lattice
      spacings propagate freely, i.e., without interaction.

PMID- 12006060
TI  - Patterns arising from the interaction between scalar and vectorial instabilities
      in two-photon resonant Kerr cavities.
AB  - We study pattern formation associated with the polarization degree of freedom of
      the electric field amplitude in a mean field model describing a nonlinear Kerr
      medium close to a two-photon resonance, placed inside a ring cavity with flat
      mirrors and driven by a coherent x-polarized plane-wave field. In the self
      focusing case, for negative detunings the pattern arises naturally from a
      codimension two bifurcation. For a critical value of the field intensity there
      are two wave numbers that become unstable simultaneously, corresponding to two
      Turing-like instabilities. Considered alone, one of the instabilities would
      originate a linearly polarized hexagonal pattern whereas the other instability is
      of pure vectorial origin and would give rise to an elliptically polarized stripe
      pattern. We show that the competition between the two wave numbers can originate
      different structures, the detuning being a natural selection parameter.

PMID- 12006061
TI  - Symmetry broken motion of a periodically driven Brownian particle: nonadiabatic
      regime.
AB  - We report a theoretical study of an overdamped Brownian particle dynamics in the
      presence of both a spatially modulated one-dimensional periodic potential U(x)
      and a periodic alternating force (AF). As the periodic potential U(x) has a low
      symmetry (a ratchet potential) the Brownian particle displays a broken symmetry
      motion with a nonzero time average velocity. By making use of the Green function
      method and a mapping to the theory of Brillouin bands the probability
      distribution P(x,t) of the particle coordinate x is derived and the nonlinear
      dependence of the macroscopic velocity on the frequency omega and the amplitude
      eta of the AF is found. In particular, our theory allows to go beyond the
      adiabatic limit (omega=0) and to explain the peculiar reversal of the velocity
      sign found previously in the numerical analysis.

PMID- 12006062
TI  - Optically realizable localized wave solutions of the homogeneous scalar wave
      equation.
AB  - One of the most frequently discussed problems in construction of localized wave
      (LW) solutions of the homogeneous scalar wave equation has been their energy
      content--the LW's generally have infinite energy content and special methods have
      to be used to obtain physically realizable wave fields. So far the problem has
      mainly been addressed as a pure mathematical one and the proposed LW's can hardly
      be implemented in optics. In this paper we propose an approach for constructing
      physically realizable LW's that have a transparent interpretation in terms of
      optical setups. It will be shown that such LW's can be derived as finite aperture
      approximations of fundamental LW's, the focus wave modes.

PMID- 12006063
TI  - Theory of critical enhancement of photorefractive beam coupling.
AB  - We develop the idea of critical enhancement of the photorefractive response near
      the threshold of parametric excitation of space-charge waves (the spatial
      subharmonics) taking into account the vectorial character of beam coupling and a
      fairly strong broadening of the nonlinear resonance owing to light absorption.
      The results of our calculations are a description of the measurable
      characteristics of critical enhancement and optimization of the experimental
      conditions for detection of anomalously high amplification gain factors in cubic
      Bi(12)SiO(20) crystals.

PMID- 12006064
TI  - Implementation of the hierarchical reference theory for simple one-component
      fluids.
AB  - Combining renormalization group theoretical ideas with the integral equation
      approach to fluid structure and thermodynamics, the hierarchical reference theory
      is known to be successful even in the vicinity of the critical point and for
      subcritical temperatures. We present here a software package independent of
      earlier programs for the application of this theory to simple fluids composed of
      particles interacting via spherically symmetrical pair potentials, restricting
      ourselves to hard-sphere reference systems. Using the hard-core Yukawa potential
      with z=1.8/sigma for illustration, we discuss our implementation and the results
      it yields, paying special attention to the core condition and emphasizing the
      decoupling assumption's role.

PMID- 12006065
TI  - Latent heat calculation of the three-dimensional q=3, 4, and 5 Potts models by
      the tensor product variational approach.
AB  - Three-dimensional (3D) q-state Potts models (q=3, 4, and 5) are studied by the
      tensor product variational approach, which is a recently developed variational
      method for 3D classical lattice models. The variational state is given by a 2D
      product of local factors, and is improved by way of self-consistent calculations
      assisted by the corner transfer matrix renormalization group. It should be noted
      that no a priori condition is imposed for the local factor. Transition
      temperatures and latent heats are calculated from the observations of
      thermodynamic functions in both ordered and disordered phases.

PMID- 12006066
TI  - Three-body bound-state calculations by the Lagrange-mesh method: selection of a
      coordinate system.
AB  - Four coordinate systems adapted to three-body problems, the relative, Jacobi,
      perimetric, and renormalized Hylleraas coordinates, are compared in bound-state
      Lagrange-mesh calculations. The convergence of the energy with respect to the
      Lagrange basis size and the filling rate of the Hamiltonian matrix are analyzed.
      Three kinds of potentials are considered: harmonic, Gaussian, and Coulomb-like
      potentials. When at most one interaction potential presents a singularity at the
      origin, Jacobi coordinates represent the best choice for three-body Lagrange-mesh
      calculations. When all three potentials contain 1/r singularities, Jacobi
      coordinates provide only a limited accuracy, and perimetric coordinates take
      over. In all cases, with a good choice of coordinates, the Lagrange-mesh method
      provides very good accuracies on the three-body ground-state energy with small
      numbers of mesh points.

PMID- 12006067
TI  - Modeling continuous processes from data.
AB  - Experimental and simulated time series are necessarily discretized in time.
      However, many real and artificial systems are more naturally modeled as
      continuous-time systems. This paper reviews the major techniques employed to
      estimate a continuous vector field from a finite discrete time series. We compare
      the performance of various methods on experimental and artificial time series and
      explore the connection between continuous (differential) and discrete (difference
      equation) systems. As part of this process we propose improvements to existing
      techniques. Our results demonstrate that the continuous-time dynamics of many
      noisy data sets can be simulated more accurately by modeling the one-step
      prediction map than by modeling the vector field. We also show that radial basis
      models provide superior results to global polynomial models.

PMID- 12006068
TI  - Bound state properties of the ground states in the DT+ and T(2)+ ions.
AB  - Recently developed multibox approach [A.M. Frolov, Phys. Rev. E 64, 036704
      (2001)] is used to construct highly accurate, bound state wave functions for the
      ground states in the heavy adiabatic ions DT+ and T(2)+. The computed variational
      energies and bound state properties have significantly higher accuracy than
      results known from earlier computations. Nevertheless, the computed and predicted
      nucleus-nucleus cusp and nucleus-nucleus delta function differ significantly even
      for the highly accurate wave functions used in this study.

PMID- 12006069
TI  - Influence of extended dynamics on phase transitions in a driven lattice gas.
AB  - Monte Carlo simulations and dynamical mean-field approximations are performed to
      study the phase transition in a driven lattice gas with nearest-neighbor
      exclusion on a square lattice. A slight extension of the microscopic dynamics
      with allowing the next-nearest-neighbor hops results in dramatic changes. Instead
      of the phase separation into high- and low-density regions in the stationary
      state the system exhibits a continuous transition belonging to the Ising
      universality class for any driving. The relevant features of the phase diagram
      are reproduced by an improved mean-field analysis.

PMID- 12006070
TI  - Noncollapsing solution below r(c) for a randomly forced particle.
AB  - We show that a noncollapsing solution below r(c) can be constructed for the
      dynamics of randomly forced particle interacting with a dissipating boundary. The
      scaling analysis predicts a divergent collision rate at the boundary for the
      noncollapsing solution. This prediction is tested numerically.

PMID- 12006071
TI  - Improved stability bound for steady-state flow in a car-following model of road
      traffic on a circular route.
AB  - This note revisits a car-following model of road traffic on a circular route that
      was studied in recent literature, and improves a stability result for steady
      state flows that was obtained in this literature. It will be shown through a
      counter example that the stability bound obtained in the literature only gives a
      sufficient condition for stability, which only becomes necessary when the number
      of cars on the route tends to infinity. We will further present a result that
      gives a necessary and sufficient condition for stability.

PMID- 12006072
TI  - Phase ordering on small-world networks with nearest-neighbor edges.
AB  - We investigate global phase coherence in a system of coupled oscillators on small
      world networks constructed from a ring with nearest-neighbor edges. The effects
      of both thermal noise and quenched randomness on phase ordering are examined and
      compared with the global coherence in the corresponding XY model without quenched
      randomness. It is found that in the appropriate regime phase ordering emerges at
      finite temperatures, even for a tiny fraction of shortcuts. The nature of the
      phase transition is also discussed.

PMID- 12006073
TI  - Computing with excitable systems in a noisy environment.
AB  - In this work we show that excitable units with biologically inspired couplings
      are capable of performing any logic operation in a noisy environment without
      synchronization.

PMID- 12006074
TI  - Generalized synchronization in directionally coupled systems with identical
      individual dynamics.
AB  - A simple chaotic flow is presented, which when driven by an identical copy of
      itself, for certain initial conditions, is able to display generalized
      synchronization instead of identical synchronization. Being that the drive and
      the response are observed in exactly the same coordinate system, generalized
      synchronization is demonstrated by means of the auxiliary system approach and by
      the conditional Lyapunov spectrum. This is interpreted in terms of changes in the
      structure of the system stationary points, caused by the coupling, which modify
      its global behavior.

PMID- 12006075
TI  - Quantum dispersion and its exponential growth of a wave packet in chaotic
      systems.
AB  - The quantum correspondence of one particular signature of classical chaos--the
      exponential instability of motion--can be characterized by the initial
      exponential growth rate of the spreading of the propagating quantum wave packet.
      The growth rate is approximately twice the classical maximum Lyapunov exponent of
      the system. In the regular case, the dispersion of the wave packet is only due to
      the usual quantum effect that should vanish in the classical limit. In contrast,
      in the chaotic case, the evolution behavior of the wave packet is due to the
      dynamical effect associated with the nonlinearity and persists as long as the
      spatial extension of the initial wave packet is kept finite.

PMID- 12006076
TI  - planck-->0 and classical-quantum correspondence in the kicked Harper model.
AB  - We investigate classical-quantum correspondence for the kicked Harper model for
      extremely small values of the Planck constant (planck). In the asymmetric case a
      pure quantum state shows a clear signature of classical diffusive as well as
      superdiffusive transitions asymptotically independent of planck. However, for the
      symmetric case, the planck independent behavior occurs only for the renormalized
      parameter (-)K=K/(2planck) with intriguing features such as a sharp transition
      from integrable to nonintegrable transport at (-)K=pi/2, a series of transitions
      at multiples of pi, and the periodicity of the transmission probability. We
      suggest that even as planck-->0, the quantum dynamics is influenced by cantori
      and additional features emerge in their absence.

PMID- 12006077
TI  - Time behavior of the secondary flow between time-periodically corotating
      cylinders: a two-frequency forcing case.
AB  - We consider the oscillatory flow between time-periodically corotating cylinders,
      in the case of a two-frequency forcing. The angular velocity Omega(t) of the
      cylinders is the sum of a low-frequency omega(1) oscillation plus a harmonic
      frequency omega(2) oscillation at a lower amplitude, Omega(t)=Omega(1)
      cos(omega(1)t)+Omega(2) cos(omega(2)t). The temporal behavior of the secondary
      flow is characterized by ultrasound Doppler velocimetry. For a single-frequency
      forcing at omega(1), above a critical amplitude Omega(1), within one cycle, the
      secondary flow measurements exhibit a spikelike behavior with several successive
      growths, dampings, and periods of quietness. The effect of the superimposed
      omega(2) frequency is the following, although if alone it would be stable: to
      sharpen the spikes, restabilizing the flow for some intervals that exhibit
      secondary flow for the single forcing at omega(1); and to induce further
      secondary flow spikes during what is a quiescent stage in the single omega(1)
      frequency forcing case. Numerical calculations for the finite-gap quasisteady
      linear stability analysis are presented and provide a good prediction of the
      times of growth and damping of the secondary flow observed experimentally during
      a flow period.

PMID- 12006078
TI  - Wavy stripes and squares in zero-Prandtl-number convection.
AB  - A simple model to explain the numerically observed behavior of chaotically
      varying stripes and square patterns in zero-Prandtl-number convection in
      Boussinesq fluid is presented. The nonlinear interaction of mutually
      perpendicular sets of wavy rolls, via higher-order modes, may lead to a
      competition between the two sets of rolls. The appearance of square patterns is
      due to a secondary forward bifurcation from a set of wavy rolls. The statistics
      of the spatially averaged energy signal shows a power-law behavior.

PMID- 12006079
TI  - Current-sheet formation in incompressible electron magnetohydrodynamics.
AB  - The nonlinear dynamics of axisymmetric, as well as helical, frozen-in vortex
      structures is investigated by the Hamiltonian method in the framework of ideal
      incompressible electron magnetohydrodynamics. For description of current-sheet
      formation from a smooth initial magnetic field, local and nonlocal nonlinear
      approximations are introduced and partially analyzed that are generalizations of
      the previously known exactly solvable local model neglecting electron inertia.

PMID- 12006080
TI  - Self-trapping of strong electromagnetic beams in relativistic plasmas.
AB  - Interaction of an intense electromagnetic (em) beam with a relativistic electron
      positron (e-p) plasma is investigated. It is shown that the thermal pressure
      brings about a fundamental change in the dynamics-localized, high amplitude, em
      field structures, not accessible to a cold (but relativistic) plasma, can now be
      formed under well-defined conditions. The possibilities of trapping em beams in
      self-guiding regimes to form stable two-dimensional solitonic structures in a
      pure e-p plasma are worked out.

PMID- 12006081
TI  - Space- and time-resolved density measurements of a high-intensity laser-produced
      plasma for x-ray laser studies.
AB  - We present a detailed study on the spatiotemporal density evolution of a plasma
      created by optical-field ionization of a high-pressure pulsed gas jet by a 10-TW,
      60-fs Ti:sapphire laser. The plasma dynamics has been studied on a 17-ns time
      scale with a 60-fs time resolution and a 5-microm space resolution using a Mach
      Zehnder interferometer. The density profile and the plasma radial expansion were
      accurately measured for conditions relevant to x-ray laser schemes in H-like
      nitrogen which were recently proposed [S. Hulin et al., Phys. Rev. E 61, 5693
      (2000)]. The results were reproduced well by hydrocode simulations that allowed
      to infer the plasma temperature.

PMID- 12006082
TI  - Beta factor in a random laser.
AB  - We develop a definition for the beta factor, the fraction of spontaneous emission
      that seeds the laser process, for a random laser. With the wavelength-dependence
      of the gain (and potentially scattering) being the only possible criterion in the
      competition between gain and loss, our concept of beta is based on the spectral
      properties of the spontaneous emission and laser light. We find beta
      approximately equal to 0.1. We discuss the apparent similarities and differences
      between the beta for a cavity and a random laser.

PMID- 12006083
TI  - Newton's laws of motion in the form of a Riccati equation.
AB  - We discuss two applications of a Riccati equation to Newton's laws of motion. The
      first one is the motion of a particle under the influence of a power law central
      potential V(r)=kr(epsilon). For zero total energy we show that the equation of
      motion can be cast in the Riccati form. We briefly show here an analogy to
      barotropic Friedmann-Robertson-Lemaitre cosmology where the expansion of the
      universe can be also shown to obey a Riccati equation. A second application in
      classical mechanics, where again the Riccati equation appears naturally, are
      problems involving quadratic friction. We use methods reminiscent to
      nonrelativistic supersymmetry to generalize and solve such problems.

PMID- 12006084
TI  - Numerical analysis of the master equation.
AB  - Applied to the master equation, the usual numerical integration methods, such as
      Runge-Kutta method, become inefficient when the rates associated with various
      transitions differ by several orders of magnitude. We introduce an integration
      scheme that remains stable with much larger time increments than can be used in
      standard methods. When only the stationary distribution is required, a direct
      iteration method is even more rapid; this method may be extended to construct the
      quasistationary distribution of a process with an absorbing state. Applications
      to birth-and-death processes reveal gains in efficiency of two or more orders of
      magnitude.

PMID- 12006085
TI  - Comment on "Scaling behavior in explosive fragmentation".
AB  - We discuss the data analysis and the conclusions based upon the analysis given in
      the paper by Diehl et al. [Phys. Rev. E 62, 4742 (2000)].

PMID- 12006087
TI  - Selenium deficiency increases the expression of inducible nitric oxide synthase
      in RAW 264.7 macrophages: role of nuclear factor-kappaB in up-regulation.
AB  - The inducible isoform of nitric oxide synthase (iNOS) is implicated in
      atherosclerosis, malignancy, rheumatoid arthritis, tissue and reperfusion
      injuries. A key determinant of the pro-oxidant versus protective effects of NO is
      the underlying redox status of the tissue. Selenoproteins, such as glutathione
      peroxidases (GPxs) and thioredoxin reductases, are key components of cellular
      defence and promote optimal antioxidant/oxidant balance. In this study, we have
      investigated the relationship between Se status, iNOS expression and NO
      production in Se-deficient and Se-supplemented RAW 264.7 macrophage cell lines.
      The cellular GPx activity, a measure of Se status, was 17-fold lower in Se
      deficient RAW 264.7 cells and the total cellular oxidative tone, as assessed by
      flow cytometry with 2',7'-dichlorodihydrofluorescein diacetate, was higher in the
      Se-deficient cells than the Se-supplemented cells. Upon lipopolysaccharide (LPS)
      stimulation of these cells in culture, we found significantly higher iNOS
      transcript and protein expression levels with an increase in NO production in Se
      deficient RAW 264.7 cells than the Se-supplemented cells. Electrophoretic
      mobility-shift assays, nuclear factor-kappaB (NF-kappaB)-luciferase reporter
      assays and Western blot analyses indicate that the increased expression of iNOS
      in Se deficiency could be due to an increased activation and consequent nuclear
      localization of the redox-sensitive transcription factor NF-kappaB. These results
      suggest an inverse relationship between cellular Se status and iNOS expression in
      LPS-stimulated RAW 264.7 cells and provide evidence for the beneficial effects of
      dietary Se supplementation in the prevention and/or treatment of oxidative-stress
      mediated inflammatory diseases.

PMID- 12006088
TI  - The family of hepatoma-derived growth factor proteins: characterization of a new
      member HRP-4 and classification of its subfamilies.
AB  - Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a family
      of polypeptides named after HDGF, which was identified by its mitogenic activity
      towards fibroblasts. In the present study, we describe a hitherto unknown HRP,
      termed HRP-4. The cDNA of bovine HRP-4 (bHRP-4) predicts a polypeptide of 235
      amino acids. Northern- and Western-blot analyses of various bovine tissues
      demonstrated that HRP-4 is only expressed in the testis. Recombinantly produced
      bHRP-4 and murine HDGF (mHDGF) histidine-tagged polypeptides display growth
      factor activity for cultured primary human fibroblasts at an optimum
      concentration of 1 ng/ml in serum-free medium. The growth-factor activity
      declines with increasing concentrations to reach background levels at 1
      microg/ml. The expression of the fusion proteins, bHRP-4-green fluorescent
      protein and mHDGF-green fluorescent protein, in HEK-293 cells demonstrates
      nuclear localization of the proteins. bHRP-4 and mHDGF bind to the
      glycosaminoglycans heparin and heparan sulphate, but not to chondroitin sulphate.
      Affinity constants determined for these interactions are between 6 and 42 nM.
      Comparison of the bHRP-4 amino acid sequence with HRP-1-3 and p52/75/lens
      epithelium-derived growth factor (LEDGF) shows that these proteins share a
      conserved N-terminal part of 91 amino acids but have C-termini of different
      lengths and charge. This demonstrates the modular structure of these proteins and
      allows its classification into three groups based on charge, size and sequence
      comparison. HRP-4, HRP-1 and HDGF are small acidic proteins, HRP-3 is a small
      basic protein, and HRP-2 and p52/75/LEDGF are larger basic proteins.

PMID- 12006089
TI  - Gap junctions and ovarian folliculogenesis.
AB  - Gap junctions are collections of intercellular membrane channels that allow
      adjacent cells to share small molecules (< 1 kDa). Gap junction channels are
      composed of connexins, a homologous family of more than 20 proteins. In
      developing follicles, gap junctions couple the growing oocyte and its surrounding
      follicle cells into a functional syncytium. This review summarizes evidence on
      the expression of various connexins in developing follicles and the likely roles
      that some of the connexins play, on the basis of findings from gene targeting
      experiments in mice. Gap junctions between cumulus cells contain predominantly
      connexin43, and this connexin has also been detected using immunoelectron
      microscopy in a small minority of gap junctions at the oocyte surface. The
      importance of connexin43 for granulosa cell function is demonstrated by the fact
      that follicles lacking this connexin arrest in early preantral stages and produce
      incompetent oocytes. Connexin37 appears to be the only connexin contributed by
      oocytes to the gap junctions coupling them with granulosa cells, and loss of this
      connexin interferes with the development of antral follicles. The expression of
      multiple connexins in developing follicles is thus likely to reflect the multiple
      functions served by gap junctional communication in folliculogenesis.

PMID- 12006090
TI  - Matrix metalloproteinases and their specific tissue inhibitors in menstruation.
AB  - The timely breakdown of extracellular matrix is essential for menstruation.
      Matrix metalloproteinases, which are able to degrade virtually all components of
      the extracellular matrix, are spatiotemporally expressed in the cyclic
      endometrium. The expression of most matrix metalloproteinases is regulated
      transcriptionally and their proteolytic activities are precisely controlled. The
      balance between matrix metalloproteinases and their specific tissue inhibitors is
      believed to be crucial for menstruation. This review focuses on the roles of
      matrix metalloproteinases and their tissue inhibitors in the initiation of
      menstruation and on the regulation of matrix metalloproteinase expression and
      activation. For example, the function of matrix metalloproteinases and their
      tissue inhibitors in endometrial re-epithelialization and angiogenesis during
      endometrial regeneration, when cell migration is facilitated to ensure
      endometrial repair, is discussed. This and other processes, although not fully
      resolved, serve to illustrate the involvement of matrix metalloproteinases and
      their tissue inhibitors in the process of menstruation.

PMID- 12006091
TI  - Progesterone stimulation of fluid absorption by the rat uterine gland.
AB  - The purpose of this study was to test the hypothesis that the steroid environment
      affects fluid absorption by the uterine glands. Laser scanning confocal
      microscopy of the distribution of an extracellular marker (fluorescein
      isothiocyanate-labelled dextran) within rat uterine glands showed that the
      endometrial glands change their fluid handling characteristics under different
      hormonal conditions. Under progesterone dominance, the glands showed an amiloride
      sensitive dextran accumulation indicating sodium-dependent fluid absorption;
      however, this was absent in the oestrogen-dominated state. The rate of fluid
      uptake in the progesterone-stimulated gland opening was estimated to be
      approximately 1 x 10(-4) cm s(-1), requiring a suction pressure of between 10 and
      20 mm Hg at the mucosal surface. This study provides the first direct evidence of
      fluid absorption by the uterine glands. Such absorption may provide the mechanism
      for closure of the uterine lumen and immobilization of the blastocyst necessary
      for implantation.

PMID- 12006092
TI  - Morphological evidence for uncontrolled proteolytic activity during the ovulatory
      process in indomethacin-treated rats.
AB  - The ovulatory process in cyclic rats was studied after prostanoid synthesis was
      blocked using indomethacin. Animals were injected at 12:00 h in pro-oestrus with
      1.0 mg indomethacin or vehicle (olive oil) and killed at 18:30 h in pro-oestrus,
      at 02:00, 09:00 and 19:00 h in oestrus and at 09:00 h in metoestrus. Additional
      rats injected with 0.5 or 4.0 mg indomethacin were killed at 09:00 h in oestrus.
      No differences in either morphology or serum LH concentrations were found between
      vehicle or indomethacin-treated rats at 18:30 h in pro-oestrus. However, from
      02:00 h in oestrus onward, the process of follicle rupture was altered
      considerably in indomethacin-treated rats, irrespective of the dose. Early
      vascular changes, observed in control rats at the apex of the follicle, were
      absent in indomethacin-treated rats. In some follicles, disruption of the theca
      layers, invasion of the perifollicular tissue by granulosa cells and follicular
      fluid, and release of the oocyte to the ovarian interstitium were observed at
      02:00 h in oestrus. A small number of follicles ruptured at the ovarian surface.
      Furthermore, invasion of interstitial tissue, rupture of blood vessel walls,
      production of emboli of granulosa cells and follicular fluid, and inflammatory
      reactions were observed in oestrus and metoestrus. The results of the present
      study demonstrate uncontrolled proteolytic activity, and indicate that abnormal
      follicle rupture (but not inhibition of follicle rupture) is responsible for
      ovulation failure in indomethacin-treated rats.

PMID- 12006093
TI  - Regulation of expression of ovarian mRNA encoding steroidogenic enzymes and
      gonadotrophin receptors by FSH and GH in hypogonadotrophic cattle.
AB  - A study was conducted to determine the effects of FSH and bovine somatotrophin on
      the expression of mRNA encoding the gonadotrophin receptors and steroidogenic
      enzymes in ovarian follicles of cattle rendered hypogonadotrophic by treatment
      with a GnRH agonist. Hereford x Friesian heifers were allotted into two
      pretreatment groups: controls (n = 10) and GnRH agonist-treated (n = 20). Ovaries
      of control cows were removed on day 2 of the first follicular wave after
      synchronized oestrus. GnRH agonist-treated heifers were given either FSH or no
      FSH. FSH was infused at 50 microg h(-1) for 48 h. Ovaries in GnRH agonist-treated
      heifers were removed at the end of exogenous hormone treatment. The control, GnRH
      agonist and GnRH agonist plus FSH treatment groups were divided further into
      bovine somatotrophin or no bovine somatotrophin treatments (n = 5 per treatment).
      Bovine somatotrophin (25 mg day(-1) by s.c. injection) was administered for 3
      days. Ovaries were scanned once a day by ultrasonography. Blood samples for
      hormone measurements were collected three times a day from oestrus until the time
      of removal of ovaries. Expression of mRNAs for the FSH and LH receptors and
      cytochrome P450 side-chain cleavage (P450scc), cytochrome P450 17alpha
      hydroxylase (P450c17) and cytochrome P450 aromatase (P450arom) enzymes was
      localized by in situ hybridization and quantified by image analysis. Ovarian
      follicular growth was arrested at < or = 4.5 mm in diameter in GnRH agonist
      treated heifers. There was no effect of bovine somatotrophin on follicular
      dynamics, gonadotrophin secretion or expression of mRNA for either the
      gonadotrophin receptors or steroidogenic enzymes. Infusion of FSH to GnRH agonist
      treated heifers increased FSH concentrations in serum to the physiological
      concentrations observed in controls and stimulated growth of follicles to a size
      similar (5.5-8.0 mm in diameter) to recruited follicles in control cows. FSH
      induced mRNA expression of P450scc and P450arom in granulosa cells of follicles
      at a smaller size (< or = 4.5 mm in diameter) than in controls and increased (P <
      0.001) expression in larger (> 4.5 mm in diameter) follicles. Expression of mRNAs
      for P450scc and P450c17 increased (P < 0.001) with increasing follicle size and
      was higher (P < 0.01) in theca cells of GnRH agonist plus FSH-treated heifers
      than in the other groups. There were no treatment differences in expression of
      FSH receptor in granulosa cells or LH receptor in theca cells, but expression of
      both receptors increased with follicle size. There was no expression of LH
      receptor in the granulosa cells of cows from any treatment group. In conclusion,
      FSH treatment in GnRH agonist-treated heifers induced similar changes in
      follicular growth to those observed during the first follicular wave, but despite
      similar peak concentrations, prolonged exposure to high FSH induced precocious
      expression of mRNAs for P450scc and P450arom in granulosa cells from small
      follicles and markedly upregulated expression of these enzymes in granulosa cells
      from recruited follicles. The results of this study demonstrate the key role that
      FSH plays in the induction of follicular growth and differentiation.

PMID- 12006094
TI  - Regulation of cyclooxygenase activity and progesterone production in the rat
      corpus luteum by inducible nitric oxide synthase.
AB  - This study explores interactions between the nitric oxide synthase (NOS) and the
      cyclooxygenase (COX) pathways in the regulation of progesterone production in
      early corpus luteum cells of rats. Nitric oxide (NO), prostaglandin E (PGE) and
      progesterone production was analysed in luteal cells of the rat corpus luteum
      exposed to inhibitors of non-specific NOS, inhibitors of inducible NOS (iNOS) and
      inhibitors of COX. Equine chorionic gonadotrophin (eCG)/hCG-primed rat corpus
      luteum cells produced NO, PGE and progesterone in a linear manner during 66 h of
      culture. Exposure of the cells to the non-specific NOS inhibitor, N(omega)-nitro
      L-arginine (0.15 mmol l(-1)) for 48 h reduced NO, PGE and progesterone production
      to 21, 32 and 60% of that of the controls, respectively (P < 0.05 to P < 0.01).
      Another non-specific NOS inhibitor, N(omega)-methyl-L-arginine, produced similar
      inhibitions. Exposure of the cultured cells to S-ethylisothiourea (1 mmol l(-1)),
      a selective inhibitor of iNOS, suppressed the production of NO by 63%, PGE by 69%
      and progesterone by 48%. These findings indicate that production of PGE is
      regulated partly by iNOS, and that progesterone is probably regulated indirectly
      by the secondary changes in PGE. The addition of arachidonic acid to N(omega)
      methyl-L-arginine-treated cells resulted in a significant increase in PGE and
      progesterone production (273 and 186%, respectively) without stimulating NO
      production. In contrast to the regulation exerted by the NO system on COX
      activity, the COX system does not modulate NO production in this model. This
      notion stems from the observation that the COX inhibitors acetylsalicylic acid (5
      mmol l(-1)) and indomethacin (5 micromol l(-1)) suppressed PGE by 86 and 89%,
      respectively, and progesterone by 34 and 57%, respectively, but failed to inhibit
      NO production. The results from the present study indicate that iNOS-mediated NO
      production is involved in stimulating PGE synthesis in rat luteal cells, which
      may upregulate progesterone production.

PMID- 12006095
TI  - Variations in modifications of sugar residues in hamster zona pellucida after in
      vivo fertilization and in vitro egg activation.
AB  - Lectins were used as probes in conjunction with quantitative analysis to
      investigate the distribution of different carbohydrate residues in hamster zona
      pellucida and their possible modification patterns after in vivo fertilization
      and in vitro egg activation. Several lectins including HPA, WGA, RCA-I, PNA, DSA,
      BSAIB(4), DBA, AAA and MAA were used to label the zona pellucida of both
      unfertilized and fertilized eggs. With the exception of PNA and BSAIB(4), the
      same lectins were also used to label the zona pellucida of oocytes activated in
      vitro. A multicomparison quantitative analysis of the density of labelling in the
      inner and outer regions of the zona pellucida before and after fertilization in
      vivo, as well as after in vitro egg activation, was performed. Of all the lectins
      studied, preferential localization of labelling by RCA-I and DSA to the inner
      zona pellucida of unfertilized eggs was observed. After in vivo fertilization,
      there was an increase in labelling in the inner region of the zona pellucida when
      thin sections of fertilized oocytes were incubated with HPA, BSAIB(4) and AAA.
      Although increased labelling by RCA-I was observed, a significant decrease in
      labelling intensity was obtained with WGA and the sequence Neu-WGA in both the
      inner and outer zona pellucida of fertilized oocytes. A significant increase in
      the density of labelling with WGA was also observed after digestion with
      neuraminidase. In parallel, when hamster oocytes activated in vitro were compared
      with those fertilized in vivo, a difference in lectin-gold labelling was observed
      in both the inner and outer region of the zona pellucida. Labelling with HPA,
      WGA, DSA and MAA increased significantly in both the inner and outer regions of
      the zona pellucida, whereas labelling by DBA significantly decreased in the inner
      portion of the zona pellucida. After neuraminidase treatment, a significant
      increase in labelling density was observed when thin sections of in vitro
      activated oocytes were incubated with WGA. These results demonstrate: (i) the
      post-fertilization modifications of major saccharidic determinants that may play
      a role in the sperm-egg interaction process of fertilization in vivo; and (ii)
      that the modified properties of zonae pellucidae of fertilized and in vitro
      activated eggs resulting from the action of hydrolytic enzymes, as well as
      glycoproteins released through exocytosis of cortical granules, are not
      identical.

PMID- 12006096
TI  - Role of myometrial activity in sperm transport through the genital tract and in
      fertilization in sows.
AB  - The effects of stimulation and suppression of uterine contractility at about the
      time of insemination on sperm distribution and fertilization in multiparous sows
      are described. For assessment of fertilization, sows were inseminated about 28 h
      before (synchronized) ovulation and killed at day 5 after ovulation (n = 53). For
      assessment of sperm distribution, sows were inseminated about 20 h before
      expected ovulation and were killed 12 h later (n = 26). At 10 min before
      insemination, sows received an intrauterine infusion of one of three solutions:
      (i) saline (control); (ii) 0.60 mg clenbuterol hydrochloride to suppress
      contractility; or (iii) 1 mg cloprostenol to stimulate contractility. Both
      clenbuterol and cloprostenol reduced median fertilization rate (P < 0.05) and
      median number of accessory sperm cells (P < 0.05). Distribution of sperm cells
      was also affected by treatments. Clenbuterol increased, and cloprostenol
      decreased, the number of sperm cells (P < 0.05) in the proximal 20 cm of the
      uterine horn and in the uterotubal junction. In addition, clenbuterol tended to
      increase and cloprostenol tended to decrease the number of sperm cells in the
      isthmus, although these effects were not significant. However, relative to the
      number of sperm cells in the uterus, clenbuterol treatment reduced the number of
      sperm cells in the uterotubal junction and oviduct, in contrast to cloprostenol.
      Cloprostenol increased the reflux of semen during insemination. It is
      hypothesized that suppression of uterine contractility increases transuterine
      transport time, reducing the ability of sperm cells to enter the uterotubal
      junction and the oviduct. Stimulation of uterine contractility above a certain
      level probably increases reflux and impedes transuterine transport of sufficient
      numbers of sperm cells.

PMID- 12006097
TI  - Role of facilitative glucose uptake in the glucose-inorganic phosphate-mediated
      retardation and inhibition of development in different strains of mouse embryos.
AB  - Mouse embryos from different strains develop differently in vitro depending on
      the composition of the culture medium, and in particular on the presence or
      absence of glucose and inorganic phosphate. Glucose is both stimulatory and
      inhibitory in certain conditions. Glucose uptake by cells can be passive, down
      concentration gradients, or active, through sodium driven pumps, or can occur
      through facilitative transport. This study investigated the effects of inhibition
      of facilitative glucose transport on the glucose-inorganic phosphate-mediated
      blocks in development in three different strains of mouse embryo, CF-1, CD-1 and
      an F2 hybrid. Development of CF-1 and CD-1 embryos is blocked in medium
      containing glucose and inorganic phosphate but not in medium containing glucose
      alone, and F2 embryos are not affected. Inhibition of facilitated glucose
      transport to the eight-cell-morula stage in CF-1 and CD-1 embryos resulted in
      development in medium containing both glucose and inorganic phosphate, indicating
      that the prevention of facilitative glucose uptake can overcome the developmental
      block. Removal of inhibition before the eight-cell-morula stage resulted in total
      arrest of CF-1 embryos and minimum development of CD-1 embryos. F2 embryos are
      not affected by inorganic phosphate and glucose and showed no response to the
      transporter inhibitor at any stage. These data support the contention that
      facilitated glucose transport is active in embryos, is phosphate-dependent and
      that its inhibition can overcome the glucose-inorganic phosphate-mediated
      developmental blocks in mouse embryos.

PMID- 12006098
TI  - Dynamics of intracellular calcium induced by lactate and glucose in rat pachytene
      spermatocytes and round spermatids.
AB  - Glycolytic metabolism in meiotic and post-meiotic spermatogenic cells shows
      differentiation-related changes. The developmental and physiological significance
      of these metabolic changes is not known. The aim of the present study was to test
      the hypothesis that glucose and lactate metabolism can modulate intracellular
      calcium [Ca2+](i) in spermatogenic cells in an opposing and dynamic manner.
      Fluorescent probes were used to measure [Ca2+](i) and pH(i), and HPLC was used to
      measure intracellular adenine nucleotides and mitochondrial sensing of ATP
      turnover. [Ca2+](i) in pachytene spermatocytes and round spermatids was modulated
      by changes in lactate and glucose concentrations in the media. The kinetics and
      magnitude of the [Ca2+](i) changes induced by lactate and glucose were different
      in meiotic and post-meiotic spermatogenic cells. The presence of glucose in the
      medium induced a decrease in pH(i) in spermatogenic cells. This glucose-induced
      pH(i) decrease occurred later than the changes in [Ca2+](i), which were also
      observed when the pH(i) decrease was inhibited, indicating that the glucose
      induced [Ca2+](i) increase was not a consequence of pH(i) changes. Hexose
      phosphorylation in glycolysis was part of the mechanism by which glucose
      metabolism induced a [Ca2+](i) increase in spermatogenic cells. The sensitivity
      of [Ca2+](i) to carbohydrate metabolism was higher in round spermatids than in
      pachytene spermatocytes. Thus, differentiation-related changes in carbohydrate
      metabolism in spermatogenic cells determine a dynamic and differential modulation
      of their [Ca2+](i) by glucose and lactate, two substrates secreted by the Sertoli
      cells.

PMID- 12006099
TI  - Gonadotrophin surge-induced upregulation of mRNA for plasminogen activator
      inhibitors 1 and 2 within bovine periovulatory follicular and luteal tissue.
AB  - The serine proteinases, tissue-type (tPA) and urokinase (uPA) plasminogen
      activator, are implicated in the ovulatory processes via their ability to convert
      plasminogen to its active form, plasmin. One mechanism for regulation of plasmin
      directed ovarian extracellular matrix remodelling during follicle rupture and
      corpus luteum formation is through inhibition of plasminogen activation by the
      plasminogen activator inhibitors (PAI-1 and PAI-2). The effect of the
      preovulatory gonadotrophin surge on the temporal and spatial regulation of
      expression of PAI-1 and PAI-2 mRNA and PAI activity in preovulatory bovine
      follicles and new corpora lutea collected at 0, 6, 12, 18, 24 and 48 h after a
      GnRH-induced gonadotrophin surge was examined. Both PAI-1 and PAI-2 mRNAs were
      upregulated markedly after the gonadotrophin surge, with the highest expression
      observed in follicles collected at about the time of ovulation (24 h) and in
      corpora lutea (48 h). PAI-1 mRNA was localized primarily to the thecal layer of
      preovulatory follicles. In contrast, PAI-2 mRNA was localized specifically to the
      granulosa cell layer. Significant PAI activity was detected in follicle extracts,
      but temporal or spatial differences in PAI activity were not detected in response
      to the gonadotrophin surge. These results indicate that PAI-1 and PAI-2 mRNAs are
      upregulated in preovulatory bovine follicles after the gonadotrophin surge in a
      cell-specific way. Regulation of PAI-1 and PAI-2 may help to control plasminogen
      activator activity associated with ovulation and early corpus luteum formation.

PMID- 12006100
TI  - Differentiation of chicken gonad as an endocrine organ: expression of LH
      receptor, FSH receptor, cytochrome P450c17 and aromatase genes.
AB  - The gonad is an endocrine organ secreting sex hormones and also a target of
      pituitary gonadotrophins. The expression of mRNAs encoding LH receptor (LHR), FSH
      receptor (FSHR), P450c17 and P450aromatase in the developing gonads of embryos
      between day 4 and day 6 of incubation was determined using a RT-PCR to elucidate
      the chicken gonad as a target organ of gonadotrophins. Although expression of
      mRNAs encoding LHR, FSHR and P450c17 was detected at day 4 of incubation in both
      sexes, mRNA encoding P450aromatase appeared at day 6 in female embryos only,
      indicating that mRNAs encoding gonadotrophin receptors can be identified before
      sexual differentiation. Quantitative PCR analysis revealed that expression of
      mRNA encoding LHR and FSHR remained low in male gonads from day 4 to day 6 of
      incubation, whereas they increased on day 6 in female gonads. The sexual
      dimorphism in the expression of mRNAs encoding LHR and FSHR was confirmed in the
      sexually differentiated gonads of embryos at day 12 of incubation (LHR in ovary
      ratio LHR in testis = 7 ratio 1; FSHR in ovary ratio FSHR in testis = 9 ratio 1).

PMID- 12006101
TI  - Seasonal changes in testicular size and serum LH, prolactin and testosterone
      concentrations in male polar bears (Ursus maritimus).
AB  - Little is known about the reproductive endocrinology of the male polar bear,
      Ursus maritimus, except that serum testosterone concentrations are high in April
      and May during the mating season and are low from August to November during the
      non-mating season. The objective of this study was to describe the relationship
      between seasonal changes in testicular size and serum concentrations of
      testosterone, LH and prolactin. Blood samples and testicular measurements were
      obtained from free-ranging male polar bears in Canada in April (n = 5) and May (n
      = 15) near Resolute Bay, Northwest Territories and near Churchill, Manitoba in
      July (n = 15) and October (n = 22). Testis size was greater in May (39.4 +/- 3.5
      cm(2)) than in October (27.3 +/- 2.0 cm(2)) (P = 0.002). Serum testosterone
      concentrations were approximately three-fold higher in April (5.8 +/- 0.8 ng ml(
      1)) than in May (1.7 +/- 0.5 ng ml(-1)), July (0.6 +/- 0.2 ng ml(-1)) and October
      (1.1 +/- 0.2 ng ml(-1)). Similarly, serum LH concentrations were high in April
      (0.14 +/- 0.04 ng ml(-1)) and low in May (0.09 +/- 0.01 ng ml(-1)), July (0.10 +/
      0.02 ng ml(-1)) and October (0.08 +/- 0.00 ng ml(-1)). Serum prolactin
      concentrations were high in April (1.9 +/- 0.3 ng ml(-1)), highest in May (2.5 +/
      0.2 ng ml(-1)), lower in July (1.3 +/- 0.1 ng ml(-1)) and lowest in October (0.8
      +/- 0.07 ng ml(-1)). The present study demonstrates a positive relationship
      between testicular size and serum concentrations of LH, prolactin and
      testosterone in the male polar bear and confirms the previously reported seasonal
      changes in serum testosterone concentrations. Data from the present study provide
      important baseline and comparative endocrine information that can be used to aid
      captive breeding programmes in zoos and to further ecological-behavioural studies
      of polar bears.

PMID- 12006102
TI  - Relationship between seasonal changes in spermatogenesis in the juvenile ostrich
      (Stuthio camelus) and the presence of the LH receptor and 3beta-hydroxysteroid
      dehydrogenase.
AB  - The immunohistochemical localization of the LH receptor and 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) was studied in the testis of the juvenile ostrich
      (Stuthio camelus) throughout a 1 year period. Spermatogenic activity of juvenile
      birds changed throughout the year, as has been reported previously for sexually
      mature birds. During the active stage of the testicular cycle, from September to
      January, spermatogenesis progressed up to the stage of formation of spermatozoa,
      although spermatozoa could not be detected in the epididymis. Leydig cells
      stained intensely with antibodies against the LH receptor and 3beta-HSD during
      the quiescent, recrudescent and active phases of the testicular cycle. During the
      regressive phase, there was a slight decrease in immunostaining for 3beta-HSD in
      these cells. These results indicate that Leydig cells in the testis of the
      juvenile ostrich are able to respond to LH and are capable of steroid synthesis.
      Furthermore, in juvenile (prepubertal) ostriches, spermatogeneic activity can be
      observed and, as in mature birds, spermatogenesis undergoes seasonal changes.

PMID- 12006104
TI  - G-protein-coupled receptors for neurotransmitter amino acids: C-terminal tails,
      crowded signalosomes.
AB  - G-protein-coupled receptors (GPCRs) represent a superfamily of highly diverse
      integral membrane proteins that transduce external signals to different
      subcellular compartments, including nuclei, via trimeric G-proteins. By
      differential activation of diffusible G(alpha) and membrane-bound G(beta)gamma
      subunits, GPCRs might act on both cytoplasmic/intracellular and plasma-membrane
      bound effector systems. The coupling efficiency and the plasma membrane
      localization of GPCRs are regulated by a variety of interacting proteins. In this
      review, we discuss recently disclosed protein interactions found with the
      cytoplasmic C-terminal tail regions of two types of presynaptic neurotransmitter
      receptors, the group III metabotropic glutamate receptors and the gamma
      aminobutyric acid type-B receptors (GABA(B)Rs). Calmodulin binding to mGluR7 and
      other group III mGluRs may provide a Ca(2+)-dependent switch for unidirectional
      (G(alpha)) versus bidirectional (G(alpha) and G(beta)gamma) signalling to
      downstream effector proteins. In addition, clustering of mGluR7 by PICK1 (protein
      interacting with C-kinase 1), a polyspecific PDZ (PSD-95/Dlg1/ZO-1) domain
      containing synaptic organizer protein, sheds light on how higher-order receptor
      complexes with regulatory enzymes (or 'signalosomes') could be formed. The
      interaction of GABA(B)Rs with the adaptor protein 14-3-3 and the transcription
      factor ATF4 (activating transcription factor 4) suggests novel regulatory
      pathways for G-protein signalling, cytoskeletal reorganization and nuclear gene
      expression: processes that may all contribute to synaptic plasticity.

PMID- 12006103
TI  - CCAAT/enhancer-binding proteins: structure, function and regulation.
AB  - CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors
      that all contain a highly conserved, basic-leucine zipper domain at the C
      terminus that is involved in dimerization and DNA binding. At least six members
      of the family have been isolated and characterized to date (C/EBP
      alpha[bond]C/EBP zeta), with further diversity produced by the generation of
      different sized polypeptides, predominantly by differential use of translation
      initiation sites, and extensive protein-protein interactions both within the
      family and with other transcription factors. The function of the C/EBPs has
      recently been investigated by a number of approaches, including studies on mice
      that lack specific members, and has identified pivotal roles of the family in the
      control of cellular proliferation and differentiation, metabolism, inflammation
      and numerous other responses, particularly in hepatocytes, adipocytes and
      haematopoietic cells. The expression of the C/EBPs is regulated at multiple
      levels during several physiological and pathophysiological conditions through the
      action of a range of factors, including hormones, mitogens, cytokines, nutrients
      and certain toxins. The mechanisms through which the C/EBP members are regulated
      during such conditions have also been the focus of several recent studies and
      have revealed an immense complexity with the potential existence of cell/tissue-
      and species-specific differences. This review deals with the structure,
      biological function and the regulation of the C/EBP family.

PMID- 12006109
TI  - Considerations for using fluorescence polarization in the screening of G protein
      coupled receptors.
AB  - Fluorescence polarization must be classified as a unique detection method
      relative to other intensity-based methods because both bound and unbound tracer
      is measured. Other fluorescence techniques require either physical removal of
      unbound tracer or a means for distinguishing only bound tracer. The presence of
      unbound tracer in the detection volume has profound consequences on how assay
      performance is gauged. The intent here is to provide tools for accurate assay
      performance assessment and to discuss some of the practical considerations
      necessary for understanding the advantages and limitations of the technology. An
      emphasis is placed on applications using G protein-coupled receptors.

PMID- 12006105
TI  - Management of obstetric anal sphincter injury: a systematic review & national
      practice survey.
AB  - BACKGROUND: We aim to establish the evidence base for the recognition and
      management of obstetric anal sphincter injury (OASI) and to compare this with
      current practice amongst UK obstetricians and coloproctologists. METHODS: A
      systematic review of the literature and a postal questionnaire survey of
      consultant obstetricians, trainee obstetricians and consultant coloproctologists
      was carried out. RESULTS: We found a wide variation in experience of repairing
      acute anal sphincter injury. The group with largest experience were consultant
      obstetricians (46.5% undertaking > or = 5 repairs/year), whilst only 10% of
      responding colorectal surgeons had similar levels of experience (p < 0.001).
      There was extensive misunderstanding in terms of the definition of obstetric anal
      sphincter injuries. Overall, trainees had a greater knowledge of the correct
      classification (p < 0.01). Observational studies suggest that a new 'overlap'
      repair using PDS sutures with antibiotic cover gives better functional results.
      However, our literature search found only one randomised controlled trial (RCT)
      on the technique of repair of OASI, which showed no difference in incidence of
      anal incontinence at three months. Despite this, there was a wide variation in
      practice, with 337(50%) consultants, 82 (55%) trainees and 80 (89%)
      coloproctologists already using the 'overlap' method for repair of a torn EAS (p
      < 0.001). Although over 50% of colorectal surgeons would undertake long-term
      follow-up of their patients, this was the practice of less than 10% of
      obstetricians (p < 0.001). Whilst over 70% of coloproctologists would recommend
      an elective caesarean section in a subsequent pregnancy, only 22% of obstetric
      consultants and 14% of trainees (p < 0.001). CONCLUSION: An agreed classification
      of OASI, development of national guidelines, formalised training,
      multidisciplinary management and further definitive research is strongly
      recommended.

PMID- 12006108
TI  - High throughput screening for cyanovirin-N mimetics binding to HIV-1 gp41.
AB  - The human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp41 is an
      important mediator of viral entry into host cells. Previous studies showed that
      the virucidal protein cyanovirin-N (CV-N) bound to both gp120 and gp41, and that
      this binding was associated with its antiviral activity. We constructed an HTS
      assay based on the interaction of europium-labeled CV-N with recombinant
      glycosylated gp41 ectodomain to support identification of small-molecule mimetics
      of CV-N that might be developed as antiviral drug leads. Primary screening of
      over 107,000 natural product extracts in the assay yielded 347 confirmed hits.
      Secondary assays eliminated extracts that bound directly to labeled CV-N or for
      which the simple sugars mannose and N-acetylglucosamine blocked the interaction
      with gp41 (lectin activity). Extracts were further prioritized based on anti-HIV
      activity and other biological, biochemical, and chemical criteria. The
      distribution of source organism taxonomy of active extracts was analyzed, as was
      the cross-correlation of activity between the CV-N-gp41 binding competition assay
      and the previously reported CV-N-gp120 binding competition assay. A limited set
      of extracts was selected for bioassay-guided fractionation.

PMID- 12006106
TI  - Oral sildenafil (Viagra) in male erectile dysfunction: use, efficacy and safety
      profile in an unselected cohort presenting to a British district general
      hospital.
AB  - INTRODUCTION: Sildenafil (Viagra) is one of the drugs used in the first line
      therapy of male erectile dysfunction (MED). We have recorded outcomes, adverse
      events and acceptability of Sildenafil (Viagra) therapy in an unselected group of
      men presenting with ED to a British district general hospital. METHODS: In this
      prospective observational study, 147 men with ED were seen since Oct 1999. Study
      patients were reviewed at 4, 12 and 52 weeks. All the patients filled the
      International Index of Erectile Function (IIEF) questionnaire and were asked
      about their willingness to pay (WTP) for treatment. RESULTS: All suitable men
      accepted Viagra as first line therapy. 91% of our patients found sildenafil
      treatment successful. 80% of these patients were willing to continue with
      sildenafil therapy. Side effect profile of sildenafil was different in this study
      with much higher incidence of headache, dyspepsia, flushing and abnormal vision.
      92% of men with ED expect to be treated by the NHS. Of those men eligible for
      treatment in the NHS, 30% qualify under the clinical categories and 18% under the
      'distress' category. Only 55% of those with cardiovascular risk factors qualify
      for NHS treatment. CONCLUSIONS: Sildenafil is widely accepted as first line
      therapy among British men with ED and has a success rate of 91%. Nearly half of
      men with ED qualify for NHS treatment. Nearly half of those with vascular risk
      factors do not qualify for NHS treatment. Most men with ED could possibly be
      managed in primary care.

PMID- 12006110
TI  - An Escherichia coli biosensor strain for amplified and high throughput detection
      of antimicrobial agents.
AB  - We report here the construction of a bacterial reporter system for high
      throughput screening of antimicrobial agents. The test organism is the
      Escherichia coli K-12 strain carrying luciferase genes luxC, luxD, luxA, luxB,
      and luxE from the bioluminescent bacterium Photorhabdus luminescens in a runaway
      replication plasmid. The replication of the plasmid can be induced, resulting in
      a change of the plasmid copy number from 1-2/cell to several hundreds per cell
      within tens of minutes. This increase in plasmid copies is independent of the
      replication of the host cells. The system will therefore amplify the effects of
      antibiotics inhibiting bacterial replication machinery, such as fluoroquinolones,
      and the inhibitory effects can be measured in real time by luminometry. The
      biosensor was compared with a strain engineered to emit light constitutively, and
      it was shown to be much more sensitive to various antibiotics than conventional
      overnight cultivation methods. The approach shows great potential for high
      throughput screening of new compounds.

PMID- 12006111
TI  - A luminescent Escherichia coli biosensor for the high throughput detection of
      beta-lactams.
AB  - A group-specific bioluminescent Escherichia coli strain for studying the action
      of beta-lactam antibiotics is described. The strain contains a plasmid, pBlaLux1,
      in which the luciferase genes from Photorhabdus luminescens are inserted under
      the control of the beta-lactam-responsive element ampR/ampC from Citrobacter
      freundii. In the presence of beta-lactams, the bacterial cells are induced to
      express the luciferase enzyme and three additional enzymes generating the
      substrate for the luciferase reaction. This biosensor for beta-lactams does not
      need any substrate or cofactor additions, and the bioluminescence can be measured
      very sensitively in real time by using a luminometer. Basic parameters affecting
      the light production and induction in the gram-negative model organism E. coli
      SNO301/pBlaLux1 by various beta-lactams were studied. The dose-response curves
      were bell shaped, indicating toxic effects for the sensor strain at high
      concentrations of beta-lactams. Various beta-lactams had fairly different assay
      ranges: ampicillin, 0.05-1.0 microg/ml; piperacillin, 0.0025-25 microg/ml;
      imipenem, 0.0025-0.25 microg/ml; cephapirin, 0.025-2.5 microg/ml; cefoxitin,
      0.0025-1.5 microg/ml; and oxacillin, 25-500 microg/ml. Also, the induction
      coefficients (signal over background noninduced control) varied considerably from
      3 to 158 in a 2-hour assay. Different non-beta-lactam antibiotics did not cause
      induction. Because the assay can be automated using microplate technologies, the
      approach may be suitable for higher throughput analysis of beta-lactam action.

PMID- 12006112
TI  - A colorimetric assay to quantify dehydrogenase activity in crude cell lysates.
AB  - Nitroblue tetrazolium (NBT) in the presence of phenazine methosulfate (PMS)
      reacts with the NADPH produced by dehydrogenases to produce an insoluble blue
      purple formazan. Endpoint assays taking advantage of this reaction have been
      successfully used to detect the activity of several dehydrogenases. Here we
      present a version of this assay suitable for determining the kinetics of 6
      phosphogluconate dehydrogenase catalysis in crude lysates of bacterial cells
      prepared in 96-well plates. Using the assay to screen a small library of variant
      6-phosphogluconate dehydrogenases generated by error-prone polymerase chain
      reaction, we were able to identify three variants with improved activity and
      thermostability over the parent enzyme. These enzymes were partially purified and
      shown to be expressed at higher levels than the parent (leading to the increase
      in activity), and all three variants were indeed more thermostable than the
      parent (temperature midpoints 4-7 degrees C higher) after purification. Thus the
      NBT-PMS assay appears suitable for screening libraries of variant dehydrogenases.

PMID- 12006113
TI  - The effect of ICER on screening methods involving CRE-mediated reporter gene
      expression.
AB  - We describe a mechanism whereby increasing levels of cAMP in Chinese hamster
      ovary (CHO) and other cell lines lead to a significant repression in cAMP
      response element (CRE)-mediated luciferase reporter gene expression. This effect
      was shown to be mediated by a modulatory factor located downstream of cyclic AMP
      (cAMP), which displayed the temporal regulation pattern of an immediate early
      gene. The expression of this inducible cAMP early repressor (ICER) was shown to
      be coincident with the time and concentration dependency of the repression of CRE
      mediated luciferase gene expression on the treatment of CHO cells with forskolin.
      Furthermore, this phenomenon was also observed in JEG and GH3 cell lines (both
      previously reported to express ICER), but not in COS-7 cells, which do not
      express ICER. These studies suggest that, in certain cell lines, expression of
      ICER can be induced at pharmacologically elevated cAMP levels, leading to a
      potent inhibition of CRE-mediated gene expression. We therefore conclude that
      screening methodologies employing such CRE-linked reporter genes (particularly in
      high-throughput screening assays) may produce false functional responses in
      certain cell lines. Moreover, such effects are likely to be exacerbated in
      screening assays in which receptors either are overexpressed or high
      concentrations of potent cAMP-elevating compounds are used.

PMID- 12006115
TI  - You are what you eat: stress, survival anxiety, the environment, and chemical
      "obesogens".

PMID- 12006116
TI  - Introducing evidence-based complementary and alternative medicine: answering the
      challenge.

PMID- 12006117
TI  - Japanese herbal medicine in patients with advanced lung cancer: prolongation of
      survival.

PMID- 12006118
TI  - Women students at Kirksville Missouri, Circa 1909.

PMID- 12006119
TI  - Interpreting conflicting findings from clinical trials of auricular acupuncture
      for cocaine addiction: does treatment context influence outcome?
AB  - OBJECTIVE: To compare findings from two consecutive clinical trials of auricular
      acupuncture for cocaine addiction conducted at the same site in order to explore
      consistency of treatment effects. SUBJECTS: One hundred and sixty-five (165)
      cocaine-dependent, methadone-maintained patients (study 1, n = 82; study 2, n =
      83). INTERVENTIONS: Subjects in both studies were randomly assigned to auricular
      acupuncture, a needle insertion control condition, or a no-needle relaxation
      control. Treatment sessions were offered five times weekly for 8 weeks. The two
      studies were equivalent in design, except that unlike study 1, study 2 offered
      subject payments for attendance and did not include weekly group counseling.
      OUTCOME MEASURES: Cocaine use assessed by three times weekly urine screens
      constituted the primary outcome. Secondary measures included retention in
      treatment, treatment attendance, treatment credibility, therapeutic alliance, and
      acute effects of treatments. RESULTS: Intent-to-treat analysis showed that
      patients assigned to acupuncture in study 1, but not in study 2, were
      significantly more likely to provide cocaine-negative urine samples relative to
      the two control conditions. CONCLUSIONS: The positive effect for acupuncture
      found in study 1 was not found in study 2. Even though the two studies were
      similar, reasons for this inconsistency cannot be determined definitively, but
      may be because of differences in psychosocial context and payment contingencies
      between the two studies, or the lack of effectiveness of acupuncture in this
      application. The need to critically consider the influence of treatment context
      and other potential moderating variables on outcome in order to draw conclusions
      regarding treatment effectiveness is discussed.

PMID- 12006120
TI  - Treatment seeking and experience with complementary/alternative medicine: a
      continuum of choice.
AB  - OBJECTIVES: To examine the treatment seeking patterns of conventional medicine
      (CM) and complementary and alternative medicine (CAM) clients across different
      health problems, and to investigate whether CAM clients with different levels of
      experience with CAM use different modes of treatment for their health issues.
      DESIGN: Three-group cross-sectional, self-administered survey study. SETTINGS AND
      SUBJECTS: One hundred and ninety-nine (199) self-selected participants sampled
      from CM and CAM clinics and offices OUTCOME MEASURES: Self-reported physical
      health problems, treatment seeking for health problems, and type of treatment
      used for each health problem (CM, CAM, or both) Results: Treatment rates for non
      life-threatening health issues were significantly associated with client group
      membership after controlling for differences in the number of health problems
      (partial r = 0.35, p < 0.0001), with the more experienced CAM clients reporting
      the highest treatment rates and the CM clients reporting the lowest rates. The
      newer CAM clients also differed significantly from the more experienced CAM
      clients in the modes of treatment used for their health issues (p < 0.0001), with
      the less experienced CAM clients relying more on CM alone (42.0%) or in
      conjunction with CAM (38.3%), whereas the experienced CAM clients used more CAM
      with CM (45.0%), or CAM alone (33.5%) than just CM alone (21.5%), for treating
      their health issues. CONCLUSIONS: CAM users may treat their health issues at
      higher rates than nonusers, independent of their greater number of health
      problems. This treatment rate increase may be associated with greater experience
      with CAM. CAM clients are not homogeneous in their choices of treatment
      modalities. Newer CAM users still rely heavily on CM treatments, whereas more
      experienced CAM users depend less on CM alone and more on CAM for treating their
      non-life-threatening health issues.

PMID- 12006121
TI  - Long-term pharmacokinetics of an extract of isoflavones from red clover
      (Trifolium pratense).
AB  - OBJECTIVES: To study the pharmacokinetics of isoflavones from red clover
      (Trifolium pratense) after long-term administration as a once-daily dietary
      supplementary. DESIGN: Fourteen (14) subjects who had been consuming a low
      isoflavone diet for 2 weeks were given an oral dose of two isoflavone tablets
      (approximately 80 mg of total isoflavones) daily for 2 weeks and appeared for a
      study day at 9:00 AM after an overnight fast on the day that they were to receive
      the last dose. Plasma samples were collected for a 48-hour period after the last
      dose. Plasma isoflavones were assayed by high-performance liquid chromatography
      (HPLC). RESULTS: Trough plasma levels were significantly higher for daidzein and
      genistein after long-term dosing than levels taken prior to the commencement of
      the study and plasma levels of isoflavones after long-term dosing were in the
      range previously reported in populations that consume an isoflavone-rich diet.
      The plasma half-lives observed after long-term administration were, in most
      cases, consistent with once-daily administration. CONCLUSIONS: Isoflavones have
      pharmacokinetic characteristics that suggest that once-daily administration is
      adequate when they are administered long-term as dietary supplements.

PMID- 12006122
TI  - A randomized, double-blind, placebo-controlled trial to determine the
      effectiveness of botanically derived inhibitors of 5-alpha-reductase in the
      treatment of androgenetic alopecia.
AB  - BACKGROUND: Androgenetic alopecia (AGA) is characterized by the structural
      miniaturization of androgen-sensitive hair follicles in susceptible individuals
      and is anatomically defined within a given pattern of the scalp. Biochemically,
      one contributing factor of this disorder is the conversion of testosterone (T) to
      dihydrotestosterone (DHT) via the enzyme 5-alpha reductase (5AR). This metabolism
      is also key to the onset and progression of benign prostatic hyperplasia (BPH).
      Furthermore, AGA has also been shown to be responsive to drugs and agents used to
      treat BPH. Of note, certain botanical compounds have previously demonstrated
      efficacy against BPH. Here, we report the first example of a placebo-controlled,
      double-blind study undertaken in order to examine the benefit of these botanical
      substances in the treatment of AGA. OBJECTIVES: The goal of this study was to
      test botanically derived 5AR inhibitors, specifically the liposterolic extract of
      Serenoa repens (LSESr) and beta-sitosterol, in the treatment of AGA. SUBJECTS:
      Included in this study were males between the ages of 23 and 64 years of age, in
      good health, with mild to moderate AGA. RESULTS: The results of this pilot study
      showed a highly positive response to treatment. The blinded investigative staff
      assessment report showed that 60% of (6/10) study subjects dosed with the active
      study formulation were rated as improved at the final visit. CONCLUSIONS: This
      study establishes the effectiveness of naturally occurring 5AR inhibitors against
      AGA for the first time, and justifies the expansion to larger trials.

PMID- 12006123
TI  - Altered states of consciousness: review of experimental data obtained with a
      multiple techniques approach.
AB  - OBJECTIVES: To investigate the psychophysiologic mechanisms of an altered state
      of consciousness (ASC) produced via systematic mental training by correlating the
      results of multiple computerized bioelectrographic measurements. DESIGN: All
      subjects were tested, using a set of modern computerized techniques comprising
      digital electroencephalography, measurement of the low-frequency bilateral
      activity of the brain, evoked bioelectrographic signals measured by computerized
      Kirlian photography (otherwise called gas discharge visualization [GDV]), self
      reporting by subjects, linguistic testing, and profiling of mood states.
      LOCATION: Sweden and Russia from 1996 to 1999. SUBJECTS: Young volunteers (61)
      who underwent systematic mental training for not less than 7 weeks. Members of
      the control group (56) were not engaged in mental training. RESULTS: All
      participants involved in the systematic mental training showed significant
      positive changes in their psychoemotional status after 7 weeks of mental
      training. All of the techniques showed specific changes that might be associated
      with an ASC in the subjects. The Kirlian (GDV) patterns showed a form of
      "explosive activation," which was stable, reproducible, and correlated with an
      ASC. This led the authors to introduce the concept of short-term activation of
      the induced bioelectrographic processes and enabled the properties of this ACS to
      be determined for the first time. There were practically no changes in the
      control group. CONCLUSIONS: ASC activation took place with harmonization of the
      biopotential field of the brain, the psychic state, and the bioenergy fields.
      This is attributed to changes in both the psychosomatic and psychoenergetic
      autoregulation. This conclusion is of vital importance for understanding what
      happens in systematic mental training and understanding the fundamentals of
      bioenergetic and psychosomatic medicine.

PMID- 12006124
TI  - A multicentered, open-label trial on the safety and efficacy of
      methylsulfonylmethane in the treatment of seasonal allergic rhinitis.
AB  - BACKGROUND: Seasonal allergic rhinitis (SAR) affects more than 23 million
      Americans annually, and current epidemiologic studies indicate that its
      prevalence within the United States is increasing. Numerous clinical observations
      and case studies have led researchers to hypothesize that methylsulfonylmethane
      (MSM) may help ameliorate the symptoms associated with SAR. OBJECTIVE: The
      primary goal of this study was to evaluate the efficacy of MSM in the reduction
      of SAR-associated symptoms. This study also examined possible adverse reactions
      associated with methylsulfonylmethane supplementation. Finally, this study
      attempted to elucidate the method of action by which MSM elicits its effect on
      allergy symptoms. DESIGN: Fifty-five (55) subjects were recruited for the study.
      All met the criteria for participation in the study. 50 subjects completed the
      study. Those subjects completing the study consumed 2,600 mg of MSM orally per
      day for 30 days. Clinical respiratory symptoms and energy levels were evaluated
      by a Seasonal Allergy Symptom Questionnaire (SASQ) at baseline and on days 7, 14,
      21, and 30. Immune and inflammatory reactions were measured by plasma
      immunoglobulin E (IgE) and C-reactive protein at baseline and on day 30. An
      additional inflammatory biomarker, plasma histamine, was measured in a subset of
      subjects (n = 5). RESULTS: Day 7 upper and total respiratory symptoms were
      reduced significantly from baseline (p < 0.01 and p < 0.005, respectively). Lower
      respiratory symptoms were significantly improved from baseline by week 3 (p <
      0.001). All respiratory improvements were maintained through the 30-day visit.
      Energy levels increased significantly by day 14 (p < 0.0001); this increase
      continued through day 30. No significant changes were observed in plasma IgE or
      histamine levels. The results of this study are promising. It would be worthwhile
      to conduct a larger, randomized, double-blind, placebo-controlled study to
      establish further if MSM would be a useful agent in the treatment of symptoms
      associated with SAR. CONCLUSION: The results of this study suggest that MSM
      supplementation of 2,600 mg/day for 30 days may be efficacious in the reduction
      of symptoms associated with SAR. Furthermore, few side effects are associated
      with the use of this compound. Recent acute and subacute chronic toxicologic data
      on the same source of MSM as used in this study, further validate the safety of
      this product.

PMID- 12006125
TI  - Toxicity study of an antidipsotropic Chinese herbal mixture in rats: NPI-028.
AB  - OBJECTIVES: To determine the potential toxicity and safety of the Chinese herbal
      medicine NPI-028 in rats following subchronic (3-month) exposure via daily oral
      consumption. DESIGN: Subchronic toxicity was evaluated in four groups of rats (n
      = 10 per group) receiving NPI-028 orally at a dose of either 0.0 (normal diet
      control), 0.5, 1.0, or 2.0 g/kg, ingested as part of their daily diet for 3
      months. NPI-028 was incorporated into powdered rat chow diet as a specific
      percent of the total diet provided each day. The primary active isoflavone
      content of NPI-028 (puerarin) used in the rat diet was also determined. OUTCOME
      MEASURES: Subchronic toxicity was assessed over a 3-month period by biweekly
      measurement of water and food intake, weight gain, and visual inspection for
      maintenance of grooming and normal behavior. At the end of the study period rats
      were euthanized and blood was obtained for hematologic and chemical analysis.
      Organs were removed for histopathologic examination. RESULTS: Rats in all three
      NPI-028 dose groups were similar to the control group in weight gain, food
      intake, and water intake over the study period. Hematology, blood chemistries,
      and organ histology in rats at all three NPI-028 doses did not significantly
      differ from control rats. Minor exceptions were elevated urea nitrogen values at
      all NPI-028 doses, and increased triglyceride and thyroid-stimulating hormone
      values in the lowest NPI-028 dose-treated group. Puerarin (used as a dietary
      isoflavone marker) content of NPI-028 was 26 mg/g dry weight. CONCLUSIONS: NPI
      028 ingested orally at doses up to 2.0 g/kg per day in the rat diet for up to 3
      months resulted in normal growth with no changes in hematologic or hepatic
      parameters, and only minor alterations in renal and blood chemistry parameters.
      There was no evidence of abnormal histology. These data suggest the long-term
      daily oral consumption of NPI-028 as a part of the daily diet for 3 months, at
      the doses studied, is safe in rats. Thus, NPI-028 may potentially be safe for
      clinical use as an antidipsotropic agent.

PMID- 12006126
TI  - Chemical toxins: a hypothesis to explain the global obesity epidemic.
AB  - The number of obese people worldwide has escalated recently, revealing a complex
      picture of significant variations among nations and different profiles among
      adults and children, regions, and occupations. The commonly held causes of
      obesity-overeating and inactivity-do not explain the current obesity epidemic.
      There is evidence of a general decrease in food consumption by humans and a
      significant decline in their overall levels of physical activity. There is also
      more evidence to indicate that the body's natural weight-control mechanisms are
      not functioning properly in obesity. Because the obesity epidemic occurred
      relatively quickly, it has been suggested that environmental causes instead of
      genetic factors maybe largely responsible. What has, up to now, been overlooked
      is that the earth's environment has changed significantly during the last few
      decades because of the exponential production and usage of synthetic organic and
      inorganic chemicals. Many of these chemicals are better known for causing weight
      loss at high levels of exposure but much lower concentrations of these same
      chemicals have powerful weight-promoting actions. This property has already been
      widely exploited commercially to produce growth hormones that fatten livestock
      and pharmaceuticals that induce weight gain in grossly underweight patients. This
      paper presents a hypothesis that the current level of human exposure to these
      chemicals may have damaged many of the body's natural weight-control mechanisms.
      Furthermore, it is posited here that these effects, together with a wide range of
      additional, possibly synergistic, factors may play a significant role in the
      worldwide obesity epidemic.

PMID- 12006127
TI  - Medical provision in the twenty-first century.

PMID- 12006128
TI  - The Fugelli tactic.

PMID- 12006129
TI  - Teaching evidence-based complementary and alternative medicine: 1. A learning
      structure for clinical decision changes.
AB  - Complementary and alternative medicine (CAM) education is at a crossroads and has
      been an area of increasing debate. Public use of CAM has risen dramatically since
      1997, with initial reports ranging from 30% to a possible 60% in the United
      States. Much attention has been directed to the education of the public regarding
      CAM, with respect to efficacy, potential harm, and integration. Far less
      attention has been paid to the education of CAM practitioners. In the current
      climate of integrative health settings, CAM practitioners should be trained to
      interact with conventional physicians, the public, and policy makers in an
      evidence-based format. In order to create communication effectively, an evidence
      based approach may provide the common ground required for all schools of thought.

PMID- 12006130
TI  - Gougerot-Carteaud still an enigma after all these years.

PMID- 12006131
TI  - An open, randomized, comparative study of oral fluconazole, itraconazole and
      terbinafine therapy in onychomycosis.
AB  - BACKGROUND/AIM: In this open, randomized and comparative study, the safety and
      efficacy of systemic fluconazole, itraconazole and terbinafine was investigated
      in 50 patients with distal subungual toenail onychomycosis diagnosed clinically
      and mycologically. The patients with positive mycology and also the patients with
      positive microscopy and negative culture were investigated. METHODS: The
      treatment duration was 3 months, and the follow-up period was 6 months. Patients
      were randomly assigned: 16 patients received 150 mg fluconazole once weekly, 18
      patients received 200 mg itraconazole twice daily with meals during the first
      week of each month, and 16 patients received 250 mg/day terbinafine during the
      treatment period. RESULTS: In a clinical evaluation, at the endpoint of the
      follow-up period, the clinical cure rates were 81.3% (13/16) in the terbinafine
      group, 77.8% (14/18) in the itraconazole group, and 37.5% (6/16) in the
      fluconazole group. The mycological cure rates were 75% (12/16), 61.1% (11/18) and
      31.2% (5/16), respectively. The overall assessment rates were 62.5% (10/16),
      61.1% (11/18) and 31.2% (5/16), respectively. Statistically significant intra
      group reductions from baseline symptom severity values were seen at the endpoint
      of treatment and at the endpoint of the follow-up period for all three treatment
      groups in onycholysis, subungual hyperkeratosis, affected-area percentage score
      and total score parameters (p < 0.001). At the endpoint of the follow-up period,
      statistically significant differences between the treatment groups were seen in
      clinical, mycological and overall assessment (p < 0.05). However, while no
      statistically significant difference between the terbinafine and itraconazole
      groups was seen, there was a clinical and statistical difference between the
      other groups and the fluconazole group. Treatment was not stopped for side
      effects such as mild gastrointestinal and central nervous system symptoms. These
      effects were noted in four patients in the fluconazole group (25%), five patients
      in the itraconazole group (27.8%), and three patients in the terbinafine group
      (18.75%). The clinical laboratory data on all three drug groups did not show any
      statistically or clinically significant intra-group changes from baseline values
      at the endpoint (p > 0.05). CONCLUSION: This comparative study of systemic
      fluconazole, itraconazole and terbinafine showed that all three drugs were
      effective and safe in the treatment of onychomycosis. However, fluconazole, at
      these doses and treatment durations, was the least effective. With regard to cost
      effectiveness, side effects and the cure rates, terbinafine could be the drug of
      choice in the short-term treatment of toenail onychomycosis.

PMID- 12006132
TI  - Lack of effect of dimethylsulphoxide in cutaneous amyloidosis.
AB  - OBJECTIVE: To evaluate dimethylsulphoxide (DMSO) as a topical therapeutic agent
      for the treatment of two major variants of primary, localized, cutaneous
      amyloidosis -- macular amyloidosis (MA) and papular/lichen amyloidosis (LA) --
      using a monocentric, open, prospective trial. METHODS: A total of 25 patients
      with histopathologically proven cutaneous amyloidosis - MA, LA and BA (biphasic
      amyloidosis) (13 MA, seven LA, five BA) were requested to undertake a once daily
      application of either 50% or 100% DMSO for 12 weeks. Progress was regularly
      assessed with a scoring system for pruritus, pigmentation and papules. RESULTS:
      In 17 (68%) cases, the scores for pruritus decreased but never completely
      disappeared in any of the patients. Lightening of the pigmentation was noted in
      only six (24%) cases and the scores for the papules were decreased in only two
      out of 12 (16.6%) patients. Post-treatment skin biopsies did not reveal a
      reduction/disappearance of the amyloid deposits. In the follow-up period, the
      relapse rate was 100%. CONCLUSION: DMSO does not have an anti-pruritic effect or
      amyloid-dissolving properties. As the results are partial and transient, it is
      concluded that DMSO is not a satisfactory treatment for cutaneous amyloidosis.

PMID- 12006133
TI  - A comparison of the effects of bath additives on the barrier function of skin in
      normal volunteer subjects.
AB  - BACKGROUND: Emollients form an occlusive layer on the skin surface, reducing
      transepidermal water loss (TEWL), thus providing a temporary restoration of
      barrier function in compromised skin. This study evaluated the ability of three
      bath additives to reduce TEWL from compromised skin. METHODS: The stratum corneum
      on areas of forearm skin was removed by the repeated application of D-Squame
      discs. After 1 hour, baseline measurements (t = 0) of TEWL were recorded before
      each arm was immersed for 10 min in a warm waterbath containing one of four
      treatments. The arms were air-dried for 20 min and the TEWL measurements
      repeated. Three further TEWL measurements were made at 30-min intervals.
      Measurements were made using a Tewameter in a controlled atmosphere. RESULTS:
      There was little difference between the products in terms of changes in mean TEWL
      values. However, when expressed relative to t = 0 values, some differences became
      apparent. The mean values for sites treated with Balmandol were lower than the
      other sites at 60, 90 and 120 min. When analysed by using the summary statistic
      AUC (area under the curve), the difference between Balmandol and water and also
      Balmandol and Eucerin was statistically significant (p < 0.05). CONCLUSION: These
      results would suggest that Balmandol has a greater effect on barrier function (as
      assessed by measurement of a reduction in TEWL values) than Eucerin.

PMID- 12006134
TI  - Treatment of vitiligo.
AB  - Vitiligo, particularly in darker skinned individuals, is a psychosocial disaster.
      With patient education, proper therapeutic selection and persistence, favorable
      repigmentation can be achieved in the majority of individuals with vitiligo.
      Attention to the activity state of the disease, the type, location and extent of
      the vitiligo must be carefully balanced against the patient's expectations, time
      commitment and assumption of risks. In this review, Dr Taneja succinctly
      summarizes the wide range of therapeutic options available today for the vitiligo
      patient.

PMID- 12006135
TI  - Confluent and reticulated papillomatosis (Gougerot-Carteaud) successfully treated
      with tacalcitol.
AB  - Confluent and reticulated papillomatosis (CRP) is a rare dermatosis of unknown
      aetiology whose relationship to Malassezia furfur is still debated. Antifungal
      agents, antibiotics, retinoids, and, more recently, calcipotriol have been
      successfully used as treatment. The authors report on a 14-year-old female with
      confluent and reticulated papillomatosis in whom M. furfur was found. Anti-fungal
      therapy eliminated the fungus, but did not achieve the disappearance of the
      lesions. Further treatment with tacalcitol was successful, supporting the theory
      that CRP might be a disorder of keratinization. To the authors' knowledge, this
      is the first patient treated with tacalcitol for this entity.

PMID- 12006136
TI  - Treatment of recalcitrant plantar warts with imiquimod.
AB  - Myrmecia are viral warts that result from the coalescence of plantar or palmar
      warts into large plaques. Treatment of these warts involves physical or chemical
      destruction of the verrucae, potent keratolytics or immunotherapy. Imiquimod 5%
      cream is a novel topical immunomodulator that has been used successfully in the
      treatment of genital and common warts. We report its successful use in a 35-year
      old immunocompetent man who had had resistant plantar warts for 15 years.

PMID- 12006137
TI  - Neutrophilic eccrine hidradenitis secondary to topotecan.
AB  - BACKGROUND: Neutrophilic eccrine hidradenitis (NEH) is a self-restricted
      inflammatory condition, usually secondary to chemotherapeutic agents and less
      frequently to other drugs such as zidovudine or various infections. NEH clinical
      features include erythematous, occasionally painful nodules and plaques.
      Histological examinations reveal neutrophilic infiltrates and degeneration of
      eccrine glands. METHODS: A 45-year-old female was treated with topotecan and
      colony-stimulating factor for ovarian cancer. RESULTS: The erythematous and
      slightly pruritic plaques on the upper and lower limbs and ear lobes appeared
      approximately 1 week after chemotherapy and spontaneously subsided in about 10
      days, only to recur after the next drug dose. A skin biopsy revealed NEH; all
      skin cultures were negative. CONCLUSION: It is believed that this patient
      developed topotecan-induced NEH; this relationship with therapy rather than the
      underlying disease rules out a paraneoplastic reaction, and negative cultures
      excluded infectious causes. In addition, since skin lesions recurred after CSF
      was discontinued, this agent was not involved. Studies relating NEH to topotecan,
      a topoisomerasa I inhibitor, have not reported such an event in the literature.

PMID- 12006138
TI  - One-week terbinafine 1% solution in pityriasis versicolor: twice-daily
      application is more effective than once-daily.

PMID- 12006139
TI  - Golden nail pigmentation.

PMID- 12006140
TI  - Effect of driving pressure and nebulizer model on aerosol output during
      intermittent delivery with a dosimeter.
AB  - Recent guidelines reinforce the need for a standardized technique during
      inhalational bronchoprovocation challenge testing. We investigated the effects of
      nebulizer model and dosimeter driving pressure on nebulizer output using a
      nebulized saline model. Four nebulizers (Hudson 1720, Salter 8900, Baxter
      Airlife, and DeVilbiss 644) were evaluated at two driving pressures (20 and 50
      pounds per square inch [psi]) via a dosimeter (Salter 700) that delivered a 0.6
      sec actuation. Output was determined gravimetrically after 20 actuations of
      saline at constant respiratory flow and volume. Output per actuation at 20 psi
      was 2.83 +/- 0.41 mg (mean +/- SD), 4.58 +/- 0.66, 4.75 +/- 0.42, and 4.75 +/-
      1.37 for the Hudson, Salter, Baxter, and DeVilbiss, respectively, and 6.75 +/-
      0.61 mg, 9.17 +/- 0.88, 9.42 +/- 1.32, and 9.83 +/- 1.75 at 50 psi. The Hudson
      delivered a lower volume than the other nebulizers (p < 0.0005). At 20 psi,
      output from the DeVilbiss had greater variability (coefficient of variation =
      28.8%) compared to the Baxter (CV = 8.8%; p = 0.045). The output was greater at
      50 psi than 20 psi for all models (p < 0.0005). These results demonstrate that,
      when choosing a nebulizer driven by a dosimeter, it is important to base that
      selection on published data describing aerosol output under different driving
      pressures.

PMID- 12006141
TI  - The effect of inlet gas temperatures on heated humidifier performance.
AB  - The aim of the current study was to determine the temperature range of gas at the
      point at which it passes into a heated humidifier within an intensive care unit
      and to experimentally examine the effect of different inlet gas temperatures on
      the performance of a heated humidifier. Various gas and ambient temperatures were
      measured in an intensive care unit and within ventilator circuits. Ventilator
      oxygen and air inlet temperatures, ventilator gas outlet temperatures, and
      humidifier gas inlet temperatures were measured in conjunction with the use of a
      number of ventilators. Ambient temperatures within the ward ranged from 22.8
      degrees C to 28.9 degrees C, while typical ward humidifier gas inlet temperatures
      ranged from 24.3 degrees C to 28.8 degrees C. Humidity output from a heated
      humidifier was then determined in an experimental setup at controlled levels of
      inlet gas temperature using a constant gas flow. A decrease in humidity
      production, from approximately 36 mg/L at a humidifier inlet gas temperature of
      18 degrees C, to 26 mg/L at a humidifier inlet gas temperature of 32 degrees C,
      was observed with increasing gas inlet temperature. We conclude that humidity
      output from a heated humidifier varies with inlet gas temperature, decreasing as
      inlet gas temperature increases. Inlet gas temperatures above 26 degrees C may
      result in inadequate humidification.

PMID- 12006142
TI  - Gamma scintigraphic evaluation of a novel budesonide dry powder inhaler using a
      validated radiolabeling technique.
AB  - A scintigraphic study was carried out to compare the lung deposition of
      budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in healthy
      volunteers. Validation of Technetium-99m ((99m)Tc) radiolabeling of the
      budesonide/lactose blend used in the Clickhaler and excipient-free budesonide
      used in the Turbuhaler was carried out using a multistage liquid impinger, and
      compared with reference unlabeled devices. Budesonide was quantified using high
      performance liquid chromatography and (99m)Tc by scintillation counting. The
      percentages (SD) of fine particles (<5.5 microm diameter) from radiolabeled and
      unlabeled devices were not significantly different (p > 0.05). Mean values for
      drug and radiolabel, respectively, were 34.6% (2.5) and 31.6% (3.8) for the
      Clickhaler, and 29.8% (5.5) and 31.4% (5 6) for the Turbuhaler. Fifteen healthy
      male volunteers received a single dose (2 x 200 microg actuations) from both
      devices in a double-blinded, double dummy, crossover study. During dosing, each
      inhalation maneuver was recorded using a computer-linked pressure transducer. To
      permit accurate determination of radiolabeled drug deposition, the lung margins
      of each volunteer were determined by Krypton-81m ((81m)Kr) gas imaging. Mean [SD]
      lung deposition for the Clickhaler (26.8% [6.8], RSD 25.2) was significantly
      greater (p < 0.001) than for the Turbuhaler (15.8% [6.6], RSD 42.2). Inspiratory
      flow rate parameters were similar for both devices with peak and mean values of
      73 and 51 L/min for the Clickhaler, and 73 and 47 L/min for the Turbuhaler,
      respectively. These results indicate that, in healthy volunteers, budesonide lung
      deposition was higher and more consistent with the Clickhaler than with the
      Turbuhaler.

PMID- 12006143
TI  - Enhanced insulin absorption in the rabbit airways and lung by sodium dioctyl
      sulfosuccinate.
AB  - The objective of this investigation was to study regional absorption of inhaled
      insulin together with an enhancer (sodium di-octyl-sulfosuccinate [DOSS]) in the
      rabbit airways and lung. Insulin was administered with or without DOSS by aerosol
      inhalation, intratracheal infusion, intranasally, sublingually, and without DOSS
      intravenously. Blood glucose and plasma levels of insulin were measured during
      100 min from the start of administration. Inhalation of insulin (3 U) with 0.25%
      or 1% DOSS decreased average blood glucose levels significantly more than
      inhalation of insulin (3 U) without DOSS. Intratracheal administration of 1.5 U
      of insulin with 0.25% DOSS in 0.3 mL of vehicle decreased the average blood
      glucose level significantly compared with intratracheal administration of 1.5 U
      of insulin and no DOSS in 0.3 mL of vehicle and compared with 1.5 U of insulin
      with 0.25% DOSS in 0.15 mL of vehicle. Intravenous insulin (1.5 U) and inhaled
      (1.5 U) insulin in 0.25% DOSS decreased average blood glucose levels
      significantly compared with intratracheal (0.15 mL), intranasal, and sublingual
      administration of 1.5 U of insulin with 0.25% DOSS. The bioavailability of
      inhaled insulin (1.5 U) with 0.25% DOSS was estimated to be 16% in comparison
      with 7% for intratracheally (0.15 mL), 1% intranasally, and 0.8% sublingually
      administered insulin (1.5 U with 0.25% DOSS), respectively. Inhaled insulin
      together with the absorption enhancer DOSS decreased the blood glucose level more
      effectively than insulin given intratracheally, intranasally, or sublingually.
      The effect on blood glucose reflected the difference in plasma insulin
      concentration for the different routes of administration.

PMID- 12006144
TI  - Carbon dioxide accumulation during small animal, whole body plethysmography:
      effects on ventilation, indices of airway function, and aerosol deposition.
AB  - Barometric (whole body) plethysmography is used to examine changes in ventilation
      and breathing pattern in unrestrained animals during exposure to therapeutic or
      toxic aerosols. Whole body plethysmographs (WBP) may be operated with a bias flow
      in order to maintain an adequate supply of oxygen and remove expired CO(2).
      However, some aerosol generation and delivery methods may require operation of
      the WBP without bias flow, which would artificially deplete aerosol
      concentration. Under these conditions, expired CO(2) accumulates in the
      plethysmograph and stimulates ventilation, increasing total aerosol deposition,
      shifting regional deposition, and significantly altering some airway function
      indices. We characterized these effects in guinea pigs using a commercially
      available 4.5-L WBP, with and without a 1 L/min bias flow. CO(2)-induced changes
      in breathing frequency (f), tidal volume (Vt), minute ventilation (Ve), and
      indices of airway function -- including enhanced pause (penh), flow derived
      parameter (FDP), and respiratory duty cycle -- were measured. Without bias flow,
      CO(2) in the plethysmograph increased steadily to 5.4% after 30 min compared to a
      steady state 0.9% with bias flow. This resulted in a moderate suppression of f,
      and significant increases in Vt and Ve by factors of 1.5 and 1.4, respectively.
      Changes in regional deposition were stimulated for 300 mg/m(3) polydisperse
      aerosols with mass median aerodynamic diameters of 0.3, 1, 3, or 7 microm and
      geometric standard deviations of 1.7. Percent increase in aerosol deposition from
      CO(2) inhalation ranged from 24% to 90%, by mass, depending on aerosol size
      distribution and respiratory tract region. In addition, fractional deposition
      shifted toward the pulmonary region. Empirical indices of airway constriction,
      penh and FDP, also were increased significantly to 1.7 and 1.3 times their
      respective baseline values. The study quantifies the effect of inadvertent
      coexposure to CO(2) on ventilation, aerosol deposition, and airway function in
      WBP evaluation of aerosol effects in airway function.

PMID- 12006145
TI  - A randomized double-blinded placebo-controlled crossover trial of nebulized
      taurolidine in adult cystic fibrosis patients infected with Burkholderia cepacia.
AB  - Burkholderia cepacia is an aggressive pathogen that colonizes cystic fibrosis
      (CF) patients, causing greatly increased morbidity and mortality. It is resistant
      to most antibiotics, but sensitive in vitro to a novel agent, taurolidine. This
      has not previously been used against B. cepacia, nor given in nebulized form. We
      assessed the effect of nebulized taurolidine on United Kingdom epidemic (ET12) B.
      cepacia infection in 20 adult CF patients attending our regional adult cystic
      fibrosis outpatient clinic using a prospective, randomized, double-blinded
      placebo-controlled crossover trial. Nebulized taurolidine (4 mL 2% solution) or
      saline (4 mL 0.9% solution) was given twice daily. Each arm lasted 4 weeks, with
      a 2-week intervening washout period. Sputum B. cepacia colony counts (primary
      outcome measure), spirometry, and symptoms (secondary outcome measures) were
      assessed. Eighteen patients completed the study. There was no change in B.
      cepacia colony counts or spirometry, nor symptom scores. We conclude that,
      although taurolidine is well tolerated in nebulized form, in this study it had no
      in vivo anti-B. cepacia activity.

PMID- 12006146
TI  - Patient perception and acceptability of multidose dry powder inhalers: a
      randomized crossover comparison of Diskus/Accuhaler with Turbuhaler.
AB  - This study was designed to provide information on correct use and preference to
      features and device handling of two multidose dry powder inhalers, the
      Diskus/Accuhaler and the Turbuhaler. A total of 169 powder-naive patients (mean
      age 40 years) with asthma or chronic obstructive pulmonary disease (COPD) were
      enrolled in a randomized crossover comparison of both inhalers. An effective use
      of either inhaler was assessed before (leaflet only) and after inhaler education.
      Ease of use especially during an attack and the presence of a dose counter were
      regarded as the most important features for an ideal inhaler. The percentage of
      correct handling maneuvers and the percentage of patients achieving 100% of
      correct maneuvers increased significantly (p < 0.001) after inhaler education in
      both devices, but percentage of correct use after the intervention was
      significantly higher for the Diskus/Accuhaler (92.6%) than for the Turbuhaler
      (89.8%; p = 0.036). Overall 60% of patients thought the Diskus/Accuhaler was
      preferable to the Turbuhaler (p < 0.001). The main reasons given were presence of
      a dose counter, perceived ease of use including ease of learning to use, design,
      and attached cover. Among those who preferred the Turbuhaler device, the main
      reason cited was small size, discreetness, and ease of holding. In the
      multivariate analysis, inhaler education (p = 0.005) and education level (p =
      0.009) were significantly associated with the percentage of correct maneuvers.
      Age, sex, or tested inhaler showed no effect on appropriateness of the inhalation
      technique.

PMID- 12006147
TI  - Mass output and particle size distribution of glucocorticosteroids emitted from
      different inhalation devices depending on various inspiratory parameters.
AB  - Efficient inhalation therapy depends on successful delivery of the drug to the
      lung. The efficacy of drug delivery is not only influenced by the characteristics
      of the inhalation device, but also by the patient's handling of the device and by
      the inspiratory maneuver achieved through the device. We analyzed the output
      characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated
      inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler
      and HFA-BDP Autohaler, respectively). Mass output and particle size distribution
      of drug aerosol delivered by the inhalers were determined depending on different
      inhalation parameters in vitro using an Andersen cascade impactor. We found that,
      beside the peak inspiratory flow (PIF), other factors such as flow acceleration
      and inhalation volume also have significant effects on aerosol generation with
      respect to mass output and particle size distribution. Thus, these parameters
      should be taken into account when a suitable device for an individual patient is
      to be selected. The dependency on inspiratory parameters was most pronounced for
      the dry powder inhalers. The Turbohaler showed by far the highest variance in
      particle output (fine particle fraction ranging from 3.4% to 22.1% of label
      claim), whereas the Diskus was less dependent on variations in inhalation (10.6%
      to 18.5% of label claim). The most constant aerosol output was found for the
      Autohaler, which also released the highest fine particle fraction (43.1% to 56.6%
      of label claim).

PMID- 12006148
TI  - Size analysis of a pressurized metered dose inhaler-delivered solution
      formulation by an Aerosizer-LD time-of-flight aerosol particle size spectrometer.
AB  - In a previous study, an Aerosizer-LD time-of-flight (TOF) aerosol spectrometer
      was shown to underestimate significantly the aerodynamic size of airborne
      particles produced following actuation of a suspension-based formulation
      delivered from a pressurized metered-dose inhaler (pMDI) via a nonelectrostatic
      valved holding chamber (VHC). It was postulated that the nonspecific nature of
      the particle detection system in terms of chemical composition was responsible
      for the inclusion of smaller non-drug-containing excipient particles in the
      measured size distribution data from this analyzer. This limitation may not apply
      to certain solution formulations in which the only particles remaining after the
      evaporation of propellant and volatile excipient (solubilizer) are composed of
      pure drug substance. Such a formulation (QVAR, HFA-formulated beclomethasone di
      propionate [BDP]) has recently become available, and the present investigation
      was therefore designed to test this hypothesis. Aerosizer-LD measured mass
      weighted size distribution data for QVAR had a mass median aerodynamic diameter
      (MMAD) close to 1.1 microm, very similar to published data for this parameter,
      based on measurement of the aerosol by cascade impactor followed by drug-specific
      assay. However, the Aerosizer-LD underestimated the spread of the size
      distribution significantly. The causes are believed to be a combination of two
      separate effects: (1) lack of sensitivity of the particle detection system to
      particles finer than about 0.7 microm aerodynamic diameter and (2) preferential
      removal of particles larger than the MMAD, either by evaporation of residual
      solvent (ethanol) or by inertial/gravitational deposition in the sampling
      arrangement upstream of the measurement zone.

PMID- 12006149
TI  - The Aerosol Society Drug Delivery to the Lungs XII. London, United Kingdom,
      December 13-14,2001. Abstracts.

PMID- 12006151
TI  - Transplantation of an indigenous neural stem cell population leading to
      hyperplasia and atypical integration.
AB  - Astrocytes exhibit neural stem cell characteristics in vitro by generating
      multipotent clones of cells. In order to see if normal cues are present in vivo
      that can direct these astrocytes to generate cells of neuronal lineage, the
      astrocytes were transplanted into the persistently neurogenic mouse subependymal
      zone/rostral migratory stream. Grafted astrocytes assumed migratory profiles,
      joined chains of indigenous neuroblasts, and migrated into the olfactory bulb.
      Additionally, however, some grafted astrocytes "homed" to the lateral ventricle
      where they became hyperplastic, forming spherical structures composed of cells of
      mixed phenotype that attached to the ventricular wall, and eventually penetrated
      and dispersed within surrounding brain parenchyma. It is proposed that, with an
      interest in the use of stem cell transplants for neurological disease, findings
      of hyperplasia and apparent atypical integration of a native population of
      multipotent astrocytic stem cells suggest the need for caution before beginning
      even autologous neural stem cell transplants.

PMID- 12006152
TI  - Production of transgenic chimera rabbit fetuses using somatic cell nuclear
      transfer.
AB  - We produced aggregate chimeric embryos between blastomeres from the somatic cell
      nuclear transfer (SCNT) embryos and blastomeres from normal embryos. The SCNT
      embryos were produced by fusing enucleated oocytes with GFP gene introduced
      fibroblast cells, which were derived from a day 16 fetus. GFP gene-introduced
      fibroblast cells were cultured and passaged four to 12 times over a period of 45
      79 days before SCNT. After transferring them into pseudopregnant recipient
      rabbits, the 15-day postcoitus fetuses were collected. We examined the existence
      of the cells derived from SCNT embryos in the fetus stage of pregnancy to detect
      the GFP gene. Fetuses that were not collected continued to develop into newborn
      rabbits. Two hundred and thirty-six chimeric embryos were produced using 39 SCNT
      morula stage embryos, and these embryos were transferred to 11 recipient rabbits.
      As a result, 27 normally developed and 16 degenerated concepti were obtained. The
      GFP gene-positive signals were detected in one of the fetuses, two of the
      placentae, and two of the degenerated concepti. In this study, we found that the
      rabbit SCNT embryos have the ability to develop and differentiate in vivo. We
      also demonstrated a novel method of producing a transgenic rabbit using SCNT.

PMID- 12006153
TI  - The use of nuclear transfer to produce transgenic pigs.
AB  - Manipulation of the pig genome has the potential to improve pig production and
      offers powerful biomedical applications. Genetic manipulation of mammals has been
      possible for over two decades, but the technology available has proven both
      difficult and inefficient. The development of new techniques to enhance
      efficiency and overcome the complications of random insertion is of importance.
      Nuclear transfer combined with homologous recombination provides a possible
      solution: precise genetic modifications in the pig genome may be induced via
      homologous recombination, and viable offspring can be produced by nuclear
      transfer using cultured transfected cell lines. The technique is still
      ineffective, but it is believed to have immense potential. One area that would
      benefit from the technology is that of xenotransplantation: transgenic pigs are
      expected to be available as organ donors in the foreseeable future.

PMID- 12006154
TI  - Gene expression patterns in bovine in vitro-produced and nuclear transfer-derived
      embryos and their implications for early development.
AB  - Bovine in vitro-produced (IVP) and nuclear transfer (NT)-derived embryos differ
      from their in vivo-developed counterparts in a number of characteristics. A
      preeminent observation is the occurrence of the large offspring syndrome, which
      is correlated with considerable embryonic fetal and postnatal losses. We
      summarize here results from our studies in which we compared gene expression
      patterns from IVP and NT-derived embryos with those from their IVP counterparts.
      Numerous aberrations were found in IVP and NT-derived embryos, including a
      complete lack of expression, an induced expression, or a significant up- or
      downregulation of a specific gene. These alterations may affect a number of
      physiological functions and are considered as a kind of stress response of the
      embryos to deficient environmental conditions. We hypothesize that the
      alterations are caused by epigenetic modifications, primarily by changes in the
      methylation patterns. Unravelling these epigenetic modifications is promising to
      reveal the underlying mechanisms of the large offspring syndrome.

PMID- 12006155
TI  - Gene transfer strategies in animal transgenesis.
AB  - Position effects in animal transgenesis have prevented the reproducible success
      and limited the initial expectations of this technique in many biotechnological
      projects. Historically, several strategies have been devised to overcome such
      position effects, including the progressive addition of regulatory elements
      belonging to the same or to a heterologous expression domain. An expression
      domain is thought to contain all regulatory elements that are needed to
      specifically control the expression of a given gene in time and space. The lack
      of profound knowledge on the chromatin structure of expression domains of
      biotechnological interest, such as mammary gland-specific genes, explains why
      most standard expression vectors have failed to drive high-level, position
      independent, and copy-number-dependent expression of transgenes in a reproducible
      manner. In contrast, the application of artificial chromosome-type constructs to
      animal transgenesis usually ensures optimal expression levels. YACs, BACs, and
      PACs have become crucial tools in animal transgenesis, allowing the inclusion of
      distant key regulatory sequences, previously unknown, that are characteristic for
      each expression domain. These elements contribute to insulating the artificial
      chromosome-type constructs from chromosomal position effects and are fundamental
      in order to guarantee the correct expression of transgenes.

PMID- 12006156
TI  - Novel approaches and hurdles to somatic cloning in cattle.
AB  - The overall efficiency of somatic cloning in cattle is still low. Many factors
      are necessary for successful birth of live offspring. Among them, the source of
      donor cells reveals the importance of the donor genotype but also the influence
      of the cell line itself. The cell cycle stage has been intensively investigated,
      and recent results indicate that, in cattle, the G0 stage of the donor nuclei is
      not a prerequisite for reprogramming, as highly proliferating cultured
      fibroblasts also result in live offspring after nuclear transfer. A technical
      approach using direct microinjection of fibroblast nuclei, instead of fusion of
      the whole cell, has proved to result in high in vitro development rates in
      cattle. However, full-term development of somatic cloned embryos is still limited
      by long-lasting effects and a high incidence of losses at periimplantation time
      (as well as in late gestation and around calving).

PMID- 12006157
TI  - The recent history of somatic cloning in mammals.
AB  - The history of somatic cell nuclear transfer (NT) in mammals is full of exciting
      experiments and findings regarding the technique and outcome of NT, despite only
      covering a period of 6 years. The production of Dolly, for the first time
      demonstrating cloning from an adult somatic cell, had a great impact on
      subsequent studies. However, the more progress we make, the more obvious it
      becomes how little we know about the processes during NT, specifically how
      reprogramming events occur. Therefore, it is certainly challenging to continue
      investigating every step of somatic cell NT more intensively, starting from the
      donor cell, (type, cell cycle, synchronization, population doublings) and
      continuing until the cloned offspring are born and even further, to see how and
      if NT has an influence on health, viability, quantitative traits, and
      reproduction of cloned individuals.

PMID- 12006158
TI  - Genome engineering using site-specific recombinases.
AB  - The targeted modification of the mammalian genome has a variety of applications
      in research, medicine, and biotechnology. Site-specific recombinases have become
      significant tools in all of these areas. Conditional gene targeting using site
      specific recombinases has enabled the functional analysis of genes, which cannot
      be inactivated in the germline. The site-specific integration of adeno-associated
      virus, a major gene therapy vehicle, relies on the recombinase activity of the
      viral rep proteins. Site-specific recombinases also allow the precise integration
      of open reading frames encoding pharmaceutically relevant proteins into highly
      active gene loci in cell lines and transgenic animals. These goals have been
      accomplished by using a variety of genetic strategies but only a few recombinase
      proteins. However, the vast repertoire of recombinases, which has recently become
      available as a result of large-scale sequencing projects, may provide a rich
      source for the development of novel strategies to precisely alter mammalian
      genomes.

PMID- 12006159
TI  - Somatic cell nuclear transfer: recent progress and challenges.
AB  - Somatic cell nuclear transfer (NT) offers new and exciting opportunities in many
      areas of research and biotechnology. However, the field as a whole is still in
      its infancy, with continuing inefficiencies in the process proving many early
      expectations premature. The technical steps of NT are complex, and success is
      highly susceptible to minor variations. Furthermore, the biological process of
      reprogramming is not fully understood, making it difficult to optimize the
      protocols for providing ideal recipient oocytes and donor cells. In this paper,
      we describe recent advances and novel approaches, which resulted in progress
      during the last year, including the birth of cloned piglets and farm animals with
      precise genetic changes. Key problems hindering further progress are addressed.

PMID- 12006160
TI  - Production of human monoclonal and polyclonal antibodies in TransChromo animals.
AB  - We have developed TransChromo (TC) technology, which enables the introduction of
      megabase-sized segments of DNA into cells. We have used this approach to derive
      mice that carry megabases of human DNA by the use of a human chromosome fragment
      (HCF) as a vector. TC technology has been applied to the construction of the TC
      Mouse,trade mark which incorporates entire human immunoglobulin (hIg) loci. TC
      Mouse expresses a fully diverse repertoire of hIgs, including all the subclasses
      of IgGs (IgG1-G4). Immunization of the TC Mouse with various human antigens
      produced antibody responses comprised of human antibodies. Furthermore, it was
      possible to obtain hybridoma clones expressing fully human antibodies specific
      for the target human antigen. However, because of the instability of the Igkappa
      locus-bearing HCF2, the efficiency of hybridoma production was less than one
      tenth of that observed in normal mice. An instant solution to this problem was to
      cross-breed the Kirin TC Mouse carrying the HCF14, which was stable in mouse
      cells, with the Medarex YAC-transgenic mouse carrying about 50% of the hIgVkappa
      gene segments as a region that is stably integrated into the mouse genome. The
      resulting mouse, dubbed the KM Mouse, performed as well as normal mice with
      regard to immune responsiveness and efficiency of hybridoma production. Another
      application of TC technology is the production of polyclonal antibodies in large
      animals such as chickens and cows. To test the efficacy of human polyclonal
      antibodies derived from TC animals, feasibility studies were performed using
      antisera and purified gamma-globulin from TC mice immunized with Pseudomonas
      aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), or Japanese
      encephalitis virus (JEV). The TC mouse-derived antisera and gamma-globulin showed
      a much higher titer and efficacy in terms of the neutralizing activity of the
      pathogens in vitro and in vivo than either human serum or gamma-globulin prepared
      from human blood.

PMID- 12006161
TI  - Stroke at high altitude: Indian experience.
AB  - Stroke is a common medical emergency. There is limited knowledge about stroke at
      high altitude. We present the clinical profile of 30 cases of stroke at high
      altitude seen at our center between November 1998 to July 2000. A detailed
      neurological and systemic examination was carried out. Cases were investigated
      with blood counts, lipid profile, cardiac evaluation, and CT scan/MRI.
      Coagulation parameters were studied in some cases. Strokes formed 13.7/1000 of
      hospital admissions from high altitude area, compared to 1.05/1000 in nonhigh
      altitude area. All our cases from high altitude area were males (serving soldiers
      of armed forces). Their mean high altitude stay was 10.2 months, and they were
      all located at heights greater than 4270 m. Age ranged from 22 to 48 years (mean
      33.4 yr). Except for smoking (in four cases), they had no preexisting risk
      factors. Twenty-two cases were of ischemic stroke, 2 of intracerebral hemorrhage,
      4 of TIA/RIND (transient ischemic attack/reversible ischemic neurological
      deficit), and 2 had cerebral venous thrombosis. Out of 30 cases, 28 were of
      "stroke in young" (<45 yr) and were compared with cases in the same age group
      from nonhigh altitude areas. Polycythemia with Hb ranging from 16.2 to 22 g.dL(
      1) was seen in 21 of these 28 cases (75%). Protein C and S deficiency was found
      in 1 case in each group. CT scan showed massive infarcts involving at least 50%
      of one cerebral hemisphere in 12 cases. Multiple infarcts were seen in one case.
      CONCLUSION: Long-term stay at high altitude is associated with higher risk of
      stroke. Although all types of stroke were seen, ischemic stroke was the
      commonest. Massive infarcts were common. Polycythemia was an important risk
      factor.

PMID- 12006162
TI  - Ginkgo biloba for the prevention of severe acute mountain sickness (AMS) starting
      one day before rapid ascent.
AB  - Previous studies suggest that 5 days of prophylactic ginkgo decreases the
      incidence of acute mountain sickness (AMS) during gradual ascent. This trial was
      designed to determine if ginkgo is an effective prophylactic agent if begun 1 day
      prior to rapid ascent. In this double-blind, randomized, placebo-controlled
      trial, 26 participants residing at sea level received ginkgo (60 mg TID) or
      placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were
      transported from sea level to the summit (4205 m) over 3 hours, including 1 hour
      at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary
      outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as
      a Lake Louise Self-report Score (LLSR) >/= 3 with headache. Subjects who
      developed severe AMS were promptly transported to lower altitude for the
      remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well
      matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21
      53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on
      placebo developed severe AMS and required descent for their safety (p = 0.021);
      all recovered without sequelae. Median LLSR at 4205 m was significantly lower for
      ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did
      not reach statistical significance for lowering incidence of AMS compared with
      placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26
      (81%) subjects developed AMS overall. This is the first study to demonstrate that
      1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity
      of AMS prior to rapid ascent from sea level to 4205 m.

PMID- 12006163
TI  - Analysis of the myoglobin gene in Tibetans living at high altitude.
AB  - Myoglobin, a protein with an important role in muscle oxidative metabolism, is
      increased in high altitude residents. In the closely related hemoglobins,
      mutations cause or contribute to human disease. Furthermore, heme-containing
      proteins may be involved in oxygen sensing. We therefore tested the hypotheses
      that myoglobin allele frequencies differed in Tibetans, a long-resident human
      high-altitude population, compared with sea-level residents, and varied in
      relation to altitude among Tibetans. We obtained the sequence of exon 2 of the
      myoglobin gene in 146 Tibetans with greater than three generations of stable
      residence at altitude in rural Tibet. We compared the frequency of known
      polymorphic sites in this gene among Tibetans living at altitudes of 3000, 3700,
      and 4500 m and to allele frequencies previously obtained in 525 residents of
      Dallas, Texas. We also examined the association between different myoglobin
      genotypes and hemoglobin concentration, used as an index of myoglobin levels. The
      frequency of the myoglobin 79A allele was higher in the high altitude compared
      with the sea-level residents, but unchanged with increasing altitude among
      Tibetans. There was no significant deviation from Hardy-Weinberg equilibrium in
      any of the Tibetan altitude groups, nor was there any association between
      myoglobin genotype and hemoglobin concentration. Screening of exon 2 of the
      myoglobin gene in high altitude Tibetans does not show novel polymorphism or
      selection for specific myoglobin alleles as a function of altitude of residence
      or hypoxic challenge.

PMID- 12006164
TI  - Failure of polycythemia-induced increase in arterial oxygen content to suppress
      the anorexic effect of simulated high altitude in the adult rat.
AB  - The anorexic effect of exposure to high altitude may be related to the reduction
      in the arterial oxygen content (Ca(O2)) induced by hypoxemia and possibly the
      associated decreased convective oxygen transport (COT). This study was then
      performed to evaluate the effects of either transfusion-induced polycythemia or
      previous acclimation to hypobaria with endogenously induced polycythemia on the
      anorexic effect of simulated high altitude (SHA) in adult female rats. Food
      consumption, expressed in g/d/100 g body weight, was reduced by 40% in rats
      exposed to 506 mbar for 4 d, as compared to control rats maintained in room air.
      Transfusion polycythemia, which significantly increased hematocrit, hemoglobin
      concentration, Ca(O2), and COT, did not change the anorexic response to the
      exposure to hypobaric air. Depression of food intake during exposure to SHA also
      occurred in rats fasted during 31 h before exposure and allowed to eat ad libitum
      for 2 h during exposure. Body mass loss was similar in 48-h fasted rats that were
      either hypoxic or normoxic. Body mass loss was similar in normoxic and hypoxic
      rats, the former eating the amount of food freely eaten by the latter. Hypoxia
      acclimated rats with endogenously induced polycythemia taken to SHA again had
      diminished food intake and lost body mass at rates that were very close to those
      found in nonacclimated ones. Exposure to SHA also led to a decrease in food
      consumption, body weight, and plasma leptin in adult female mice. Analysis of
      data suggest that body mass loss that accompanies SHA-induced hypoxia is due to
      hypophagia and that experimental manipulation of the blood oxygen transport
      capacity cannot ameliorate it. Leptin does not appear to be an inducer of the
      anorexic response to hypoxia, at least in mice and rats.

PMID- 12006165
TI  - Potential use of oxygen enrichment of room air in mountain resorts.
AB  - Oxygen enrichment of room air has proved to be valuable for people who need to
      work at altitudes of 4000 m and above. In the present study the feasibility of
      using the same technique in ski and other mountain resorts at the lower altitudes
      of 2500 to 4000 m is considered. Although many people find these altitudes
      invigorating, some are distressed by the hypoxia, especially at night. The
      analysis shows that all resorts up to an altitude of 3250 m (10,600 ft) can have
      the equivalent altitude reduced to 1000 m (3280 ft) by oxygen enrichment without
      incurring a fire hazard. (The equivalent altitude is that which provides the same
      inspired P(O2) during air breathing.) Even resorts or laboratories as high as
      4250 m can have the equivalent altitude safely reduced to 1500 m, that is, lower
      than the altitude of Denver, Colorado. This application of oxygen enrichment is
      likely to be most valuable for improving sleep and assisting in the initial
      acclimatization process.

PMID- 12006166
TI  - Brief report: pressure support ventilation during an ascent and on the summit of
      Mt. Everest? A theoretical approach.
AB  - At extreme altitude, air has an almost identical composition compared to air at
      sea level, while its pressure is altitude-dependently lower. When supplementary
      oxygen is used to achieve an acceptable inspiratory pressure of oxygen (PI(O2))
      during climbing, the barometric pressure difference to lower altitudes is not
      compensated for. In this report, we tried theoretically to apply pressure support
      ventilation (PSV) to partially compensate for low barometric pressures. PSV is
      widely used for respiratory home care and is applicable via a nasal mask. Since
      there are light-weight units with long battery lives on the market, we speculated
      that these units may to some extent replace bottled oxygen. PSV was in theory
      applied at barometric pressures of 400 torr (Everest Base Camp), 284 torr (South
      Col), and 253 torr (summit of Mt. Everest). We found that during PSV at a mean
      airway pressure of 16.5 torr on the summit of Mt. Everest, a fraction of inspired
      oxygen (FI(O2)) of 0.34 sufficed to achieve an alveolar partial pressure (PA(O2))
      of 67 torr. PSV increases PI(O2) by 3.5 torr, which in theory elevates the
      maximum oxygen consumption (V(O2max)) by 218 mL.min(-1) in an acclimatized
      climber in this setting. An additional benefit of PSV at extreme altitude may
      come from the unloading of the respiratory muscles.

PMID- 12006167
TI  - Delirium at high altitude.
AB  - A 35-year-old man on a trek to the Mount Everest region of Nepal presented with a
      sudden, acute confusional state at an altitude of about 5000 m. Although
      described at higher altitudes, delirium presenting alone has not been documented
      at 5000 m or at lower high altitudes. The differential diagnosis which includes
      acute mountain sickness and high altitude cerebral edema is discussed. Finally,
      the importance of travelling with a reliable partner and using proper insurance
      is emphasized in treks to the Himalayas.

PMID- 12006168
TI  - Report on the Fourth International Conference "Hypoxia in Medicine," Geneva,
      Switzerland, September 26-28, 2001.

PMID- 12006169
TI  - Griffith Pugh, pioneer Everest physiologist.
AB  - Lewis Griffith Cresswell Evans Pugh (1909-1994), best known as the physiologist
      on the successful 1953 British Everest Expedition, inspired a generation of
      scientists in the field of altitude medicine and physiology in the decades after
      World War II. This paper details his early life, his introduction to exercise
      physiology during the war, and his crucially important work in preparation for
      the Everest expedition on Cho Oyu in 1952. Pugh's other great contribution to
      altitude physiology was as scientific leader of the 1960-1961 Himalayan
      Scientific and Mountaineering Expedition (the Silver Hut), and the origins and
      results of this important expedition are discussed. He had a major and continuing
      interest in the physiology of cold, especially in real-life situations in
      Antarctica, exposure to cold wet conditions on hills in Britain, and in long
      distance swimming. He also extended his interest to Olympic athletes at moderate
      altitude (Mexico City) and to heat stress in athletes. Pugh's strength as a
      physiologist was his readiness to move from laboratory to fieldwork with ease and
      his rigor in applying the highest standards in both situations. He led by example
      in both his willingness to act as a subject for experiments and in his attention
      to detail. He was not an establishment figure; he was critical of authority and
      well known for his eccentricity, but he inspired great loyalty in those who
      worked with him.

PMID- 12006170
TI  - Leukonychia following high altitude exposure.

PMID- 12006172
TI  - Abstracts of the V World Congress on Mountain Medicine and High Altitude
      Physiology, and the VIII Congress of the Spanish Society of Medicine and Mountain
      Rescue. Barcelona, Spain, April 18-22, 2002.

PMID- 12006173
TI  - Emerging role of carbon monoxide in physiologic and pathophysiologic states.
AB  - The discovery of nitric oxide in the 1980s unraveled the novel concept then that
      an endogenous production of a gaseous substance such as nitric oxide can impart
      critical physiologic functions in a variety of biological and pathological
      processes. Interestingly though, we have known for a longer period of time that
      there exists another gaseous molecule, carbon monoxide (CO), that can be
      generated endogenously. The heme oxygenase enzyme system generates the majority,
      if not, all of the endogenous CO. Accumulating data in recent years have lent an
      intriguing supposition that we need to regard CO beyond the old paradigm that it
      imparts only toxicity and lethality to organisms. Instead, we need to consider
      CO, at low physiologic concentration, to play critical physiologic roles in
      various pathophysiologic states. This forum will review this double-edge sword of
      CO.

PMID- 12006174
TI  - Heme oxygenase activity modulates vascular endothelial growth factor synthesis in
      vascular smooth muscle cells.
AB  - Hypoxia, cytokines, and nitric oxide (NO) stimulate the generation of vascular
      endothelial growth factor (VEGF) and induce heme oxygenase-1 (HO-1) expression in
      vascular tissue. HO-1 degrades heme to carbon monoxide (CO), iron, and
      biliverdin, the latter being reduced to bilirubin by biliverdin reductase. In the
      present study, we investigated the role of HO-1 in the modulation of VEGF
      synthesis in rat vascular smooth muscle cells (VSMC). In VSMC stimulated with
      cytokines, inhibition of NO production significantly, but not completely, reduced
      VEGF release. In contrast, inhibition of HO activity by tin protoporphyrin IX
      (SnPPIX) totally prevented cytokine-induced increase in VEGF, despite an
      augmented synthesis of intracellular NO. Stimulation of HO-1 activity by hemin
      enhanced VEGF production; this effect was abrogated by blockade of the HO
      pathway. Similarly, VEGF synthesis induced by hypoxia was down-regulated by
      SnPPIX, but not by inhibitors of NO synthase. To elucidate further a direct
      involvement of HO-1 in the observed effects, we generated transfected cells that
      overexpressed the HO-1 gene. Notably, these cells synthesized significantly more
      VEGF protein than cells transfected with a control gene. Among the products of HO
      1, biliverdin and bilirubin showed no effect, whereas iron ions inhibited VEGF
      synthesis. Exposure of cells to 1% CO resulted in a marked accumulation of VEGF
      (20-fold increase) over the basal level. Our data indicate that HO-1 activity
      influences the generation of VEGF in VSMC in both normoxic and hypoxic
      conditions. As CO and iron, respectively the inducer and the inhibitor of VEGF
      synthesis, are concomitantly produced during the degradation of heme, these data
      indicate that HO by-products may differentially modulate VEGF production.

PMID- 12006175
TI  - Differential modulation by exogenous carbon monoxide of TNF-alpha stimulated
      mitogen-activated protein kinases in rat pulmonary artery endothelial cells.
AB  - Heme oxygenase-1 (HO-1) is an enzyme that is highly inducible by various cellular
      stressors, especially oxidant injury. Our laboratory and others have demonstrated
      that induction of HO-1 exerts an antiinflammatory effect both in vitro and in
      vivo. We hypothesized that carbon monoxide (CO), a major catalytic byproduct of
      heme catalysis by HO-1, may mediate this antiinflammatory effect by modulating
      signal transduction pathways, in particular the mitogen-activated protein (MAP)
      kinase pathway. Confluent primary cultures of rat pulmonary artery endothelial
      cells (RPAEC) were treated with tumor necrosis factor-alpha (TNF-alpha; 50
      ng/ml), and whole-cell extracts were assayed for phosphorylated ERK1/2, JNK1/2,
      and p38 MAP kinases. These three major MAP kinase pathways were activated by TNF
      alpha in a time-dependent manner. RPAEC treated with TNF-alpha in the presence of
      a low concentration of CO (1%) exhibited marked attenuation of the
      phosphorylation of ERK1/2 MAP kinase when compared with cells treated with TNF
      alpha alone. A similar effect was seen on the upstream MEK 1/2 kinase.
      Interestingly, CO (1%) accentuated TNF-alpha-induced phosphorylated p38 MAP
      kinase. These effects of exogenous CO on the ERK1/2 and p38 systems could be
      replicated by overexpression of HO-1 in RPAEC, using an adenoviral vector. As
      these MAP kinases are implicated in the regulation of various inflammatory
      molecules and adhesion molecules, our data provide a potential mechanism by which
      HO-1, acting via CO, may modulate the inflammatory response by differential
      activation of the MAP kinase pathway.

PMID- 12006176
TI  - Activation of the mouse heme oxygenase-1 gene by 15-deoxy-Delta(12,14)
      prostaglandin J(2) is mediated by the stress response elements and transcription
      factor Nrf2.
AB  - The mechanism of heme oxygenase-1 (ho-1) gene activation by 15-deoxy-Delta(12,14)
      prostaglandin J(2) (15d-PGJ(2)) was examined. 15d-PGJ(2) stimulated expression of
      HO-1 mRNA and protein and of a mouse ho-1 gene promoter/luciferase fusion
      construct (HO15luc) in a dose-dependent manner in mouse hepatoma (Hepa) cells.
      HO15luc expression was not effected by troglitazone, a peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) ligand, but induction by 15d-PGJ(2) was
      abrogated by the antioxidant N-acetylcysteine. The primary 15d-PGJ(2) responsive
      sequences were localized to a 5' distal enhancer (E1) and identified as the
      stress-response element, previously shown to mediate ho-1 activation by several
      agents, including heme and heavy metals. Treatment of Hepa cells with 15d-PGJ(2)
      stimulated stress-response element-binding activity as judged by electrophoretic
      mobility shift assays. Antibody "supershift" experiments identified NF-E2 related
      factor 2 (Nrf2), but not Fos, Jun, or activating transcription factor/cyclic AMP
      response element binding protein transcription factors, within the 15d-PGJ(2)
      induced complexes. Similarly, a dominant-negative mutant of Nrf2, but not of c
      Jun or c-Fos, abrogated 15d-PGJ(2)-stimulated E1 transcription activity. Finally,
      prior induction of HO-1 in RAW264.7 mouse macrophages by 15d-PGJ(2) attenuated
      cell death caused by diesel exhaust particle extracts. These results demonstrate
      that induction of mouse HO-1 expression by 15d-PGJ(2) is independent of PPAR
      gamma but dependent on oxidative stress, is regulated by the oxidative stress
      activated transcription factor Nrf2, and provides cytoprotective activity.

PMID- 12006177
TI  - Biological chemistry of carbon monoxide.
AB  - Carbon monoxide (CO) has many effects in biology due to its complex biochemical
      activities. These actions of CO depend primarily on its ability to bind heme
      proteins (Hp) and to inhibit or alter their biochemical functions. Whether CO is
      derived from exogenous or endogenous sources, its cellular activity is related to
      its concentration and the concentration of molecular O(2), as well as to the
      availability of reduced transition metals such as Fe(II). In this respect, the
      CO/O(2) ratio and O(2)-dependent changes in local oxidation-reduction state
      assume critical importance in determining the physiological effects of CO by
      affecting the functions of specific Hp. By interacting with Hp, CO influences
      electron-transport reactions in a variety of ways, which can produce either
      prooxidant or antioxidant effects. Similarly, Hp relationships also govern how
      changes in CO concentration influence the physiological and pathological effects
      of nitric oxide and the relationships of the two biologically active gases to
      metal-catalyzed oxidations. This article provides a brief update on the
      biochemistry of CO as it relates to Hp binding, chemical oxidative processes, and
      cellular function.

PMID- 12006178
TI  - Measurement of endogenous carbon monoxide formation in biological systems.
AB  - Endogenous carbon monoxide (CO) formation has been measured in different
      biological systems using a variety of analytical procedures. The methods include
      gas chromatography-reduction gas detection, gas chromatography-mass spectroscopic
      detection, laser sensor-infrared absorption, UV-visible spectrophotometric
      measurement of CO-hemoglobin or CO-myoglobin complex, and formation of (14)CO
      from (14)C-heme formed following [2-(14)C]glycine administration. CO formation
      ranged from a low of 0.029 nmol/mg of protein/h in chorionic villi of term human
      placenta to a high of 0.28 nmol/mg of protein/h in rat olfactory receptor neurons
      in culture and rat liver perfusate.

PMID- 12006179
TI  - Cerebrovascular effects of carbon monoxide.
AB  - This review examines the influence of endogenous and exogenous carbon monoxide
      (CO) on the cerebral circulation. Although CO generated from neuronal heme
      oxygenase can modulate neurotransmission, evidence supporting its role in
      cerebral vasodilation is limited. In newborn piglets, heme oxygenase is enriched
      in microvessels and contributes to hypoxic vasodilation. Low CO concentrations
      dilate piglet arterioles by opening calcium-activated potassium channels. With
      inhalation of CO and formation of carboxyhemoglobin, cerebral vasodilation can be
      greater than that occurring with hypoxic hypoxia at equivalent reductions of
      arterial oxygen content. This additional vasodilation is probably attributable to
      additional release of hypoxic vasodilators secondary to increased oxyhemoglobin
      affinity, although direct effects of CO on cerebral arterioles may also occur.
      When CO exposure is prolonged, cerebral endothelium undergoes oxidant stress as
      evident by nitrotyrosine formation. As CO levels increase, modest decreases in
      oxygen consumption are detectable, which may reflect CO or nitric oxide
      interactions with cytochrome oxidase in regions with very low oxygen
      availability. If subsequent CO concentration increases sufficiently to depress
      cardiac function and limit cerebral perfusion, cerebral oxygen consumption
      becomes further reduced, and oxidant stress becomes amplified by leukocyte
      sequestration and xanthine oxidase activity with consequent lipid peroxidation.
      Specific regions of the brain, such as central white matter, globus pallidus, and
      hippocampus, are selectively vulnerable to CO toxicity, but whether the
      mechanisms involved in selective injury differ from other forms of hypoxia
      ischemia needs to be clarified.

PMID- 12006180
TI  - Hypoxia and carbon monoxide in the vasculature.
AB  - Hypoxia is sensed by all mammalian cells and elicits a variety of adaptive and
      pathophysiological responses at the molecular and cellular level. For the
      pulmonary vasculature, hypoxia causes increased vasoconstriction and vessel-wall
      remodeling. These responses are mediated by complex intracellular cascades
      leading to altered gene expression and cell-cell interaction. Hypoxia transiently
      increases the transcriptional rate of the heme oxygenase-1 (HO-1) gene, resulting
      in increased production of carbon monoxide (CO) and bilirubin. CO has
      vasodilatory and antiinflammatory properties in the vasculature, whereas
      bilirubin is an antioxidant. Both enzymatic products could thus modulate the
      hypoxic cellular response. Accumulating data suggest that CO inhibits the hypoxic
      induction of genes encoding vasoconstrictors and smooth muscle cell mitogens in
      the early hypoxic phase. During chronic hypoxia, low CO levels tilt the balance
      toward increased production of growth factors and vasoconstrictors that promote
      vessel-wall remodeling. Mice null in the HO-1 gene manifest decreased tolerance
      to hypoxia with right ventricular dilatation and infarction, whereas targeted
      lung overexpression of HO-1 prevents hypoxia-induced inflammatory responses and
      protects against the development of pulmonary hypertension. Such observations
      point to CO as a critical modulator of the body's adaptive responses to hypoxia.

PMID- 12006181
TI  - Cross talk between carbon monoxide and nitric oxide.
AB  - Carbon monoxide and nitric oxide are two endogenously produced gases that can act
      as second messenger molecules. Heme oxygenase and nitric oxide synthase are the
      enzyme systems responsible for generating carbon monoxide and nitric oxide,
      respectively. Both carbon monoxide and nitric oxide share similar properties,
      such as the ability to activate soluble guanylate cyclase to increase cyclic GMP.
      It is becoming increasingly clear that these two gases do not always work
      independently, but rather can modulate each other's activity. Although much is
      known about the heme oxygenase/carbon monoxide and nitric oxide synthase/nitric
      oxide pathways, how these two important systems interact is less well understood.
      This review attempts to define the current known relationship between carbon
      monoxide and nitric oxide as it relates to their production and physiological
      function.

PMID- 12006182
TI  - Carbon monoxide: innovative anti-inflammatory properties of an age-old gas
      molecule.
AB  - Observations of the effects of carbon monoxide (CO) on mammalian systems have
      been known for thousands of years. To be sure, CO is deadly under certain
      conditions and concentrations, but perhaps as the data presented here will make
      clear, it also possesses other diverse functional and immunomodulatory
      properties. This review, together with the other reviews in this issue, will
      detail that over the past three decades, fundamental functional role(s) for this
      gas molecule are beginning to emerge. This review outlines that at low
      concentrations, exogenously administered CO is a molecule involved in the
      regulation of the inflammatory response in a variety of disease models. CO has
      been shown to modulate such cellular functions as cytokine production, cell
      proliferation and apoptosis, protecting the lungs and hearts of rodents from such
      stressors as endotoxin, ischemia/reperfusion injury, cardiac xenograft rejection,
      and asthma. Although the mechanism by which this simple diatomic gas provides
      this protection remains obscure, the conclusions are the same: CO at low
      concentrations, concentrations that are well below those that would otherwise
      create toxic effects, is proving beneficial in models of acute injury. CO, akin
      to nitric oxide, is proving to be an extraordinary signaling molecule generated
      by the cell that is vital in the regulation of cellular homeostasis.

PMID- 12006183
TI  - Modulation of endothelial cell apoptosis by heme oxygenase-1-derived carbon
      monoxide.
AB  - It is well established that expression of heme oxygenase-1 (HO-1) acts in a
      cytoprotective manner in a variety of cell types, including in endothelial cells
      (EC). We have recently shown that HO-1 expression protects EC from undergoing
      apoptosis. We have also shown that the antiapoptotic effect of HO-1 is mediated
      through heme catabolism into the gas carbon monoxide (CO). In this review, we
      discuss the possible molecular mechanisms by which HO-1-derived CO suppresses EC
      apoptosis. We will review data suggesting that the antiapoptotic effect of CO
      acts through the activation of the p38 mitogen-activated protein kinase signal
      transduction pathway and requires the activation of the transcription factor
      nuclear factor-kappa B (NF-kappa B), as well as the expression of a subset of NF
      kappa B-dependent antiapoptotic genes.

PMID- 12006184
TI  - Carbon monoxide and human disease.
AB  - Carbon monoxide is produced endogenously in humans through the breakdown of
      hemoglobin by heme oxygenase. Although originally thought to be a superfluous by
      product of heme catabolism, carbon monoxide is now known to play a central role
      in many aspects of human health and disease. The functions of carbon monoxide
      that have been described to date are myriad, including blood pressure regulation,
      maintenance of organ-specific vascular tone, neurotransmission, stress response,
      platelet activation, and smooth muscle relaxation. This review outlines what is
      known to date about carbon monoxide as it relates to human disease.

PMID- 12006185
TI  - Selenium and the regulation of cell signaling, growth, and survival: molecular
      and mechanistic aspects.
AB  - In the past 30 years, it has been recognized that dietary selenium (Se) is
      essential for the normal function of many of the systems of the body.
      Furthermore, low Se intake can have deleterious effects on several aspects of
      human and animal health. The importance of Se is characterized in its role as a
      constituent of several key antioxidant and redox enzyme families. Most of the
      effects of Se are probably mediated by selenoproteins, which have the
      micronutrient covalently incorporated into the protein. The purpose of this
      review is to examine basic mechanisms by which Se regulates cell growth, gene
      transcription, cell signaling, and cell death. We start with the historical
      background to Se. The synthesis and function of selenoproteins are described,
      followed by details of the dietary sources of Se and Se status in different parts
      of the world, together with the clinical effects of Se deficiency and toxicity.
      We consider some aspects of the molecular mechanisms by which Se modulates cell
      growth, intracellular signaling, and gene transcription.

PMID- 12006188
TI  - Re-epithelialization of the skin following CO2 laser resurfacing.
AB  - Wound healing following CO(2) laser resurfacing of the face is a complex process
      which must involve a rapid replacement of the ablated epidermis to protect the
      underlying structures in the skin from desiccation and deeper injury. The
      majority of cells that regenerate the epidermis come from the hair follicles, and
      cell movement out of the follicles is monitored using immunofluorescence with
      antibodies to keratin 17, an intermediate filament protein expressed in the
      migrating front of cells. This migration is enhanced with occlusive dressings
      used immediately after the resurfacing procedure. Skin biopsies have been
      examined at multiple time points following resurfacing, and re-epithelialization
      begins by 48 h in skin that has been occluded. Skin that has been left open with
      no treatment forms an eschar and has no keratinocyte migration at 48 h, thus
      displaying delayed wound healing.

PMID- 12006189
TI  - A double-blind, side-by-side comparison study of low fluence long pulse dye laser
      to coolant treatment for wrinkling of the cheeks.
AB  - BACKGROUND: Nonablative laser resurfacing with various lasers and light sources
      can improve skin texture and fine lines. The 595 nm pulsed dye laser has been
      reported to improve rhytides through nonablative mechanisms, minimizing the side
      effects and recovery period associated with traditional ablative resurfacing
      techniques. OBJECTIVE: The purpose of this study was to investigate the efficacy
      of the long pulse flashlamp pumped pulsed dye laser (LPDL) in improving rhytides
      and stimulating collagen synthesis and dermal remodeling. METHODS: The cheeks of
      15 women with moderate to severe photoaging were treated on one side with a
      series of four monthly LPDL treatments, while the contralateral cheek was treated
      with cryogen coolant only. Clinical grading was performed at monthly intervals
      for up to 3 months after the fourth LPDL treatment. Skin biopsy before treatment
      and at 4-6 weeks was also performed for histologic evaluation and staining for
      type I procollagen. RESULTS: Eleven of 15 patients demonstrated improvement of
      the laser-treated cheek while only three of 15 patients the demonstrated
      improvement on the cryogen-treated cheek. A statistically significant (p =
      0.0035) improvement in clinical grading of photodamage was noted in the treated
      side versus the control. In those patients who improved with LPDL treatment, an
      improvement of 18.1% in the mean pre- and post-treatment clinical grading scores
      was observed. Histologic evaluation demonstrated an increase in activated
      fibroblasts with positive procollagen staining on the LPDL-treated cheek.
      CONCLUSION: The 595 nm LPDL may be used in the treatment of moderate to severe
      wrinkles. A mild improvement may be expected with minimal to no side effects.

PMID- 12006190
TI  - A pilot investigation to subjectively measure treatment effect and side-effect
      profile of non-ablative skin remodeling using a 532 nm, 2 ms pulse-duration
      laser.
AB  - BACKGROUND AND OBJECTIVE: Carbon dioxide laser skin resurfacing has become a
      standard treatment for wrinkles and sun-damaged skin. This ablative treatment,
      however, is associated with undesirable complications and long recovery times. A
      growing body of evidence suggests that dermal inflammation and subsequent
      collagen formation can be stimulated without removal of the epidermis, raising
      the possibility of effective non-ablative skin remodeling for mild to moderately
      photodamaged skin. MATERIALS AND METHODS: This preliminary study was performed to
      evaluate the safety and subject satisfaction of non-ablative skin remodeling
      using a 532 nm, 2 ms pulse-duration, frequency-doubled Nd:YAG laser. Subjects
      with mild-to-deep lip wrinkles and mild-moderate acne scarring were treated one
      half of their lip (wrinkles) or cheek (acne scarring), leaving the other side as
      an untreated control. Subjects were treated at 3-6 week intervals for an average
      of three treatments. Subjective assessment of improvement was estimated by
      subject self-evaluation of the percentage improvement over baseline, and a
      blinded observer attempted to identify the treated side on physical examination.
      RESULTS: Subjective assessment revealed an average improvement of 51.4% and 53.6%
      for upper lip wrinkles and facial acne scarring, respectively. Side effects were
      limited to transient erythema that resolved over 0.25-2 hours following
      treatment. CONCLUSIONS: These results demonstrate that non-ablative treatment
      with the 532 nm, 2 ms pulse-duration Nd:YAG laser results in subjective
      improvement of rhytides and acne scarring, with a high safety profile.

PMID- 12006191
TI  - Necrobiosis lipoidica diabeticorum treated with the pulsed dye laser.
AB  - BACKGROUND AND OBJECTIVE: Different treatment modalities have been advocated for
      necrobiosis lipoidica diabeticorum but clinical response is unpredictable. The
      purpose of this study was to evaluate the usefulness of pulsed dye laser (Candela
      SPTL, Irvine, MA, USA) in the treatment of an area of necrobiosis lipoidica of 4
      cm in diameter on the anterior aspect of the leg in a non-diabetic patient.
      MATERIALS AND METHODS: A spot test was made at 6.0, 6.5 and 7.0 J/cm(2) energy
      fluences and the best energy fluence was selected after a 2-month postoperative
      evaluation. The patient received three treatment sessions with a fluence of 6.5
      J/cm(2), 585-nm wavelength, 5-mm spot size, and 450 micro(s) pulse duration at 8
      week intervals. The patient was given routine skin care advice with emollient
      cream and sunscreen (SPF 15) until the following session. RESULTS: Overall
      cosmetic improvement was achieved, with a decrease of erythema and
      telangiectasis, and stabilization in terms of progression (size) in the left half
      of the lesion, with no modification of atrophy or pigmentary changes. The right
      upper quadrant of the lesion showed an erythematous peripheral halo with minimal
      reduction in the erythema and telangiectasia, and discrete size increase.
      CONCLUSION: Pulsed dye laser may be a useful treatment for improving the
      telangiectasia and erythematous component of necrobiosis lipoidica.

PMID- 12006192
TI  - Treatment of leg and face veins with a cryogen spray variable pulse width 1064-nm
      Nd:YAG laser--a prospective study of 47 patients.
AB  - OBJECTIVE: Throughout the 1990s laser treatment of leg veins has been a
      challenge. Newer, longer wavelength lasers capable of delivering high fluences
      with larger spot sizes, with variable pulse width have shown promising
      preliminary results. Experience with these lasers for the treatment of facial
      telangiectasia and periorbital reticular veins is even more scant. To the
      authors' knowledge this is the first prospective study to evaluate a variable
      pulse width, cryogen spray-equipped 1064-nm Nd:YAG laser for the treatment of
      both leg and face veins, including larger periorbital reticular veins. METHODS: A
      total of 47 volunteers aged 32-67 years (30 skin type I-V with leg telangiectasia
      and reticular veins, and 17 skin type I-IV with face telangiectasia and reticular
      periorbital veins) were treated with the Nd:YAG laser. For leg vein patients, two
      to three sets of different leg veins were treated with a maximum of three
      treatments. Patients were examined 1 week after each treatment and at 1, 2, and 3
      months after the last treatment. All face vein patients received one treatment
      and were examined at 1 month post treatment. Treatment parameters for both leg
      and face veins varied with the size of vessels being treated. Pre and post
      treatment 35-mm photographs were taken. Improvement was judged by two experienced
      physicians both visually on patients and by comparison of pre and post treatment
      photos. Results were graded as percentage resolution, in five groups: 0%, 0-25%,
      25-50%, 50-75% and 75-100%. RESULTS: In all, 23 of 30 patients completed the leg
      vein segment of the study. A total of 41 leg vein sites were treated. Greater
      than 75% improvement was observed at 85% of the treated sites; greater than 50%
      improvement was observed at 95% of the treated sites; less than 25% improvement
      was observed at 5% of the treated sites. In all, 17 of 17 patients completed the
      face vein segment of the study. A total of 32 sites were treated (24 on cheeks,
      nose, and chin telangiectasia and eight periorbital reticular veins). Greater
      than 75% improvement was observed at 97% of the treated sites; greater than 50%
      improvement was observed at 100% of the treated sites. Notably, 100% of the
      facial reticular veins treated had essentially 100% resolution. Pain during
      treatment was variably perceived by patients, but occasionally was sufficient for
      patients to decline further treatment. Transient hemosiderin pigmentation, as
      seen with sclerotherapy, was common with larger vessels. CONCLUSION: The cryogen
      spray-equipped 1064-nm Nd:YAG laser was remarkably effective and safe for skin
      type I-V patients. Excellent results for leg veins, approaching sclerotherapy
      outcomes, were obtained for both 0.3-1.5-mm telangiectasia and larger 1.5-3-mm
      reticular veins. Furthermore, this laser is also an outstanding tool for
      treatment of facial telangiectasia with little if any risk of purpura. For the
      first time it appears that there is a safe and effective treatment for 1-2-mm
      periorbital reticular veins. However, the use of topical anesthesia may be needed
      for some patients.

PMID- 12006193
TI  - Locobase repair cream following CO2 laser skin resurfacing reduces interstitial
      fluid oozing.
AB  - BACKGROUND: The cosmetic result after laser resurfacing depends not only on the
      type of laser and the technique used, but also on post-treatment care. The
      efficacy of Locobase Repair((R)) cream, which improves skin barrier function due
      to its content of natural skin analogue fats and cholesterol, was investigated.
      METHODS: A total of 18 Caucasian patients underwent resurfacing for acne scars.
      Laser treatment was performed with a Sharplan 1020 CO(2) laser and a Silk Touch
      scanner. Locobase Repair cream (a water-in-oil cream with 63% lipids including
      natural components of stratum corneum: cholesterol, ceramide and free fatty
      acids) was applied daily to one side of the face and petrolatum was applied to
      the other. In addition, both sides were treated with a 2% fusidic acid cream.
      RESULTS: There was a significant reduction of oozing during the first 2 days
      after CO(2) laser treatment on the sides treated with Locobase Repair cream (p <
      0.05), CO(2) laser while from day 3 to day 7 no differences were demonstrated
      between the Locobase Repair cream and petrolatum. For the other parameters scored
      (scaling, oedema, erythema and pain), no significant differences between Locobase
      Repair cream and petrolatum were found. Furthermore, no significant differences
      were found between the two creams regarding the duration of wound healing and
      final cosmetic outcome. In all, 62% of the patients preferred to use Locobase
      Repair cream during the postoperative period, and 11% preferred petrolatum. The
      remaining 27% expressed no preferences. CONCLUSION: The use of Locobase Repair
      cream as a post laser resurfacing treatment reduces tissue fluid oozing during
      the first 2 postoperative days, indicating a quick restoration of skin barrier
      and hence possibly a reduction in the incidence of wound infections as well as
      enhancing patient compliance due to less fluid oozing.

PMID- 12006194
TI  - Severe phototoxic reaction to laser treatment in a patient taking St John's Wort.
AB  - Potential patients in the developed world are increasingly turning to treatment
      with herbs. One of the most popular herbs taken for depression is St John's Wort,
      which contains the potential photosensitizer hypericin. 'Hypericism' is a term
      used to describe a state of skin sensitivity to visible light in animals
      following ingestion of hypericin-containing plants and feed. A patient who
      developed a severe phototoxic reaction to laser light at 532 nm and also an
      exaggerated and unexpectedly severe response to pulsed dye laser light at 585 nm
      is described. It subsequently transpired that the patient was taking St John's
      Wort at the time of laser treatment.

PMID- 12006196
TI  - Lessons from psychotherapy research for psychological interventions for people
      with schizophrenia.
AB  - This article argues that psychological interventions for people with
      schizophrenia could be developed by being informed by research from the wider
      psychotherapy literature. We specifically argue that research on these
      interventions has ignored two key themes from this wider literature: first, the
      contention that differing models of intervention broadly result in similar
      outcomes, known as the 'equivalent outcomes paradox'; and second, the phenomenon
      of 'investigator allegiance' whereby the conclusions that may safely be drawn
      from comparative research are compromised by researchers' unwitting bias. We
      present evidence indicating that both these themes from the wider literature may
      be applicable to the literature on psychological interventions for schizophrenia
      and that schizophrenia treatment research should incorporate some of the lessons
      already learned in studies of other disorders. We conclude by arguing that
      psychological interventions for people with schizophrenia should be based on
      unbiased evidence and that interpretation of the evidence base should not be
      hindered by dogma or ideology from any quarter.

PMID- 12006197
TI  - Aberrant social relations in the personality disorders.
AB  - Research on the interpersonal aspects of personality disorders (PDs) has
      generally sought to describe them in terms of behavioural dispositions, often
      mapping these dispositions onto the interpersonal circumplex. The present study,
      in contrast, tested a theory that accounts for PDs as systematic disturbances in
      relationships between people. Self-reports of 57 participants experiencing
      significant interpersonal difficulties showed many predicted associations between
      PD symptoms and aberrant enactment of four elementary forms of social
      relationships (Fiske, 1991). Symptoms were associated with aberrant motivations
      for, and cognitive implementations of, these 'relational models', and with
      difficulties conducting them. These associations were comparable in strength to,
      but largely independent of, those obtained with a circumplex measure. Aberrations
      of authority- and equality-based relationships were central to many PDs, but not
      captured well by the circumplex. A relational analysis affords a fruitful and
      largely unexplored perspective on PDs.

PMID- 12006198
TI  - Psychometric validation of the State Scale of Dissociation (SSD).
AB  - Although dissociative phenomena are often transient features of mental states,
      existing measures of dissociation are designed to measure enduring traits. A new
      present-state self-report measure, sensitive to changes in dissociative states,
      was therefore developed and psychometrically validated. Fifty-six items were
      formulated to measure state features, and sorted according to seven subscales:
      derealization, depersonalization, identity confusion, identity alteration,
      conversion, amnesia and hypermnesia. The State Scale of Dissociation (SSD) was
      administered with other psychiatric scales (DES, BDI, BAI, SCI-PANSS) to 130
      participants with DSM-IV major depressive disorder schizophrenia, alcohol
      withdrawal, dissociative disorders and controls. In these sample populations, the
      SSD was demonstrated as a valid and reliable measure of changes in and the
      severity of dissociative states. Discriminant validity, content, concurrent,
      predictive, internal criterion-related, internal construct and convergent
      validities, and internal consistency and split-half reliability were confirmed
      statistically. Clinical observations of dissociative states, and their
      comorbidity with symptoms of depression and psychotic illness, were confirmed
      empirically. The SSD, an acceptable, valid and reliable scale measuring state
      features of dissociation at the time of completion, was obtained. This is a
      prerequisite for further investigation of correlations between changes in
      dissociative states and concurrent physiological parameters.

PMID- 12006199
TI  - Dissociative experiences and their correlates in young non-patients.
AB  - The relationship between dissociation and some of its potential correlates and
      antecedents was explored. Young medical students (N = 276) completed the
      Dissociative Experiences Scale (DES), Parental Bonding Instrument (PBI), 20-item
      Toronto Alexithymia Scale (TAS-20) and Munich Personality Test (MPT). The
      findings indicate that both personality characteristics (such as alexithymia and
      neuroticism) and, to a modest degree, environmental factors in terms of the lack
      of parental care contribute to the dissociation variance.

PMID- 12006200
TI  - Families of homicide victims: psychiatric responses and help-seeking.
AB  - The number of homicides in the UK is increasing: 850 homicides were recorded in
      England and Wales last year, but little is known about their impact on surviving
      family members. This study describes their psychological and social effects.
      Relatives seeking help from Victim Support were surveyed about their experiences,
      responses and help-seeking and asked to complete a number of psychological
      measures. Victim Support workers provided additional information. High levels of
      post-traumatic stress symptomatology and generalized distress were identified, as
      well as an increase in prescribed psychotropic medication. Other effects included
      increases in anger and irritability, cigarette consumption and loss of
      employment. However, few family members had been referred for professional
      treatment.

PMID- 12006201
TI  - Adult attachment: what are the underlying dimensions?
AB  - Using a community sample of 115 young adults, this study applied a range of
      statistical techniques to five measures of adult attachment to gain a better
      understanding of what they assess. First, we determined comparability of
      measures, using both categorical and dimensional approaches to model the
      association. Agreement among classifications was modest. Next, we examined the
      relation of attachment classifications and attachment measure subscale scores to
      criterion variables (i.e. dyadic adjustment, interpersonal sensitivity and
      severity of psychiatric symptoms). Classification predicted severity of
      psychological symptoms better than it predicted other measures of adjustment.
      Finally, using a principal components analysis, we mapped the relationship among
      underlying constructs, the subscales of the five measures and three criterion
      measures of psychological adjustment. We discuss our findings from the
      perspective of underlying constructs of attachment insecurity and strategy for
      coping with insecurity in relationships, noting implications for further
      research.

PMID- 12006202
TI  - Made of stone: a view of Parkinson 'off' periods.
AB  - Parkinson's disease is a neurological condition, managed symptomatically by
      medications aimed at the underlying dopaminergic deficit. After several years of
      treatment, some sufferers experience marked fluctuations in symptom control,
      including akinetic or 'off' periods. A sample of 15 Parkinson disease sufferers
      who experienced off periods participated in a small-scale study examining their
      experience and the coping strategies used. There was a trend for those
      experiencing significant levels of distress to make more frequent use of
      'attempted activity' coping strategies, responses that may inadvertently
      exacerbate distress. Clinical implications for adjuvant psychological techniques
      are discussed.

PMID- 12006203
TI  - Illness understanding, causal attributions and emotional reactions in wives of
      myocardial infarction patients.
AB  - This study addresses lay illness understanding and attributions, including
      attribution of blame, in wives of myocardial infarction (MI) patients concerning
      the causes of MI. The present study also investigates the association between
      illness attributions and emotional adjustment, and the associations of relevant
      third variables with illness attributions. A sample of 37 wives were interviewed
      during the acute phase of the illness, three months and 10 years post-index MI.
      Attributions of the MI to multiple causes were common with an strong emphasis on
      psychosocial risk factors, but attributional content showed a low consistency
      over time. In retrospect, the wives believed they could have done more to prevent
      the MI, but self-blame was not a significant issue. However, they blamed the
      patient for not taking preventive actions. Attributions were not related to
      background and illness characteristics or denial in any strong and consistent
      manner. In a short-term perspective, attributing the MI to stress causes and
      husbands' personality was associated with worse emotional adjustment. Also, the
      use of magical explanations and blame of the patient were related to a poorer
      emotional outcome for the wife. The causal attributions made by the wives during
      the acute phase did not influence the emotional adjustment after 10 years.

PMID- 12006206
TI  - Ex vivo expansion of human UC blood primitive hematopoietic progenitors and
      transplantable stem cells using human primary BM stromal cells and human AB
      serum.
AB  - BACKGROUND: In vitro maintenance and expansion of human hematopoietic stem cells
      is crucial for many clinical applications, and investigators have been using
      xenogeneic, especially murine, stromal cells for stem-cell expansion. In
      addition, many such culture systems utilize FCS-containing medium or serum-free
      medium that contains human- or animal-derived proteins. However, the possible
      transmission of infectious diseases has led to a debate about the safety of the
      delivery of grafts expanded in culture using cells and proteins of allogeneic or
      xenogeneic origin. Using primary human BM stromal cells, we have established an
      AB serum-based co-culture system to expand human primitive progenitors and
      transplantable stem cells. METHODS: Cord blood CD34+ cells were cultured on a
      monolayer of human BM-derived primary stromal cells with thrombopoietin (TPO),
      stem-cell factor (SCF) and flt3/flk2 ligand (FL) in the presence of either FCS or
      AB serum. One to three weeks later, cells were examined for total cells, CD34+
      cells, CD34+ CD38- cells, and clonogenic progenitors. SCID mouse reconstituting
      cell (SRC) activity was also studied. RESULTS: Three weeks of culture with TPO,
      SCF, and FL supported more than a 250-fold expansion of CD34+ cells, CD34+ CD38-
      cells and CFU-C, regardless of the kind of serum used. SRC assay revealed that
      transplantable stem cells were moderately expanded as well. DISCUSSION: This ex
      vivo expansion system should prove valuable in clinical settings in which stromal
      cells and serum are available from recipients or stem-cell donors.

PMID- 12006207
TI  - Selection of autologous CD4+ T-cells for adoptive T-cell substitution in patients
      with CD23+ B-cell CLL.
AB  - BACKGROUND: B-cell CLL (B-CLL) is accompanied by a progressive decrease in
      cellular immune functions, and treatment-related immunosuppression can further
      aggravate T-cell immunodeficiency. To reduce the risks of T-cell depletion, it
      seems feasible to collect autologous CD4+ cells at an early disease stage and
      subsequently reinfuse them during periods of profound T-cell depletion. METHOD:
      We describe a two-step cell-selection method to obtain highly enriched CD4+ T
      cells from leukapheresis compounds of patients with CD23+ B-CLL. The double
      selection procedure was performed using the CellPro Ceperate device, and
      consisted of CD4+ selection followed by CD23 purging to further remove
      contaminating CD23+ B-cells from the CD4+ cell fraction. The results of eight
      runs performed with leukapheresis material obtained from eight patients with
      CD23+ B-CLL at different disease stages are presented. RESULTS: The CD4/CD23
      double cell-selection procedure resulted in the purification of > 90% CD4+ cells.
      Median recovery of CD4+ T lymphocytes after selection was 46%, and was negatively
      affected by the initial tumor cell load. The final T-cell fraction still
      contained lymphocytes of the B-CLL clone, as determined by FACS and PCR. The cell
      processing procedure had no impact on T-cell function, as assessed by the in
      vitro production of the cytokine interferon-gamma. Moreover, the selected CD4+
      cells retained their capacity to co-stimulate mitogen-induced B-cell IgG
      production in vitro. CONCLUSION: The described CD4 selection/CD23 depletion
      strategy is a suitable approach to obtaining high numbers of functional active
      autologous CD4+ T cells for adoptive T-cell transfer in patients with CD23+ BCLL.

PMID- 12006208
TI  - The storage and re-infusion of autologous blood and BM as back-up following
      failed primary hematopoietic stem-cell transplantation: a survey of European
      practice.
AB  - BACKGROUND: Traditionally, autologous BM or PBSC have been stored as a secondary
      source ('back-up') of hematopoietic stem cells (HSC) prior to allogeneic and
      autologous HSC transplantation. METHOD: We conducted an audit of a single
      transplant center practice for providing back-up HSC and compared this practice
      with other European centers. Laboratory records relating to the collection and re
      infusion of consecutive HSC harvests were reviewed for 515 transplants (300
      autologous and 215 allogeneic HSC transplants). RESULTS: In our experience, 2.3%
      (five of 215) of allogeneic HSC transplants required secondary HSC rescue for
      failure to engraft or graft failure (MUD, n = 2; un-manipulated sibling BMT, n =
      1; T-cell depleted sibling BMT, n = 2). For autologous transplants, 4.7% (14 of
      300) required rescue due to failure to engraft or late graft failure (ABMT for
      AML, n = 8; CD34+ cell selection/ex vivo expanded, n = 4; ABMT/PBSCT, n = 2).
      Among the European centers, 69.7% replied to a postal questionnaire,
      demonstrating that 81.4% and 45.6% of centers stored a secondary HSC source for
      manipulated and unmanipulated MUD BMT, respectively; 50% and 11.6% of centers
      stored a secondary source of HSC for manipulated and unmanipulated matched
      sibling BMT, respectively; 36.4% and 12.7% of centers stored HSC for manipulated
      and unmanipulated matched sibling PBSCT, respectively. In the autologous setting,
      15.2% and 62.1% of centers stored back-up for unmanipulated and manipulated BMT,
      respectively and 19.5% and 68.5% stored back-up for unmanipulated and manipulated
      PBSCT, respectively, when myeloablative conditioning regimens were used.
      DISCUSSION: These data suggest that a small minority of patients require a
      secondary source of HSC rescue, most commonly in transplants with higher risk of
      graft failure. This is reflected in the practice across Europe of storing 'back
      up' HSC. Guidelines should accommodate the need for storage of a secondary source
      of HSC only in those transplants associated with a higher risk of graft failure,
      especially in relation to graft engineering.

PMID- 12006209
TI  - Isolex 300i CD34-selected cells to support multiple cycles of high-dose therapy.
AB  - BACKGROUND: We have previously reported that repeated cycles of high-dose therapy
      (HDT), can be supported by unmanipulated autologous PBPC. Here we investigate
      whether purified CD34+ cells, obtained by immunomagnetic separation using the
      Isolex 300i device, can support such therapy. METHODS: Twenty-nine consecutive
      patients with metastatic breast cancer had PBPC mobilized and harvested following
      chemotherapy and G-CSF (10 microg/kg per day). Patients with > 4.0 x 10(6)/kg
      CD34+ cells in the apheresis product underwent CD34-selection using the Isolex
      300i (v2.0) device. All cells collected were equally divided into three aliquots
      and cryopreserved. Patients who did not achieve this threshold had unmanipulated
      cells collected and stored. Patients subsequently received three cycles of HDT
      with paclitaxel (175 mg/m2), thiotepa (300 mg/m2) and either ifosfamide (10 g/m2)
      or cyclophosphamide (4 g/m2). It was intended for patients to receive CD34
      selected cells to support each of the three cycles of HDT (i.e 1/3 for each
      cycle) and to compare hemopoietic recovery between patients receiving CD34
      selected cells or unmanipulated cells. RESULTS: Thirteen of the 29 patients (45%)
      did not mobilize sufficient CD34+ cells to undergo CD34-selection. The remaining
      16 patients underwent CD34-selection with a median purity of 84.3% (range: 16.3
      96.1%) and yield of 34% (range: 1-60%). Fifteen of these patients proceeded to
      HDT and 42 of the planned 45 cycles were administered. Nine patients had all
      three HDT cycles supported by CD34-selected cells. The median number of CD34
      selected cells (x 10(6)/kg) infused per cycle was 1.5 (range: 0.04-3.01). Three
      of the 15 patients required infusion of 'back-up' unmanipulated cells because of
      delayed neutrophil recovery. Of the 13 patients whose PBPCs did not undergo CD34+
      cell selection, 11 proceeded to HDT with a median of 3.2 x 10(6)/kg (range: 2.0
      4.4) unselected cells infused per cycle and 31 of 33 planned cycles were
      delivered. When hemopoietic recovery was compared between cycles of HDT supported
      by CD34-selected (n = 34) and unmanipulated cells (n = 31), there was a modest
      slowing in the patients receiving CD34-selected cells; time to ANC > 1.0 x
      10(9)/L = 11 days versus 10 days (P = 0.0122) and platelets > 20 x 10(9)/L = 14
      days versus 13 days (P = 0.0009). No difference in recovery to 50 x 10(9)/L was
      observed (P = 0.54). CONCLUSION: We have demonstrated that Isolex 300i CD34
      selected cells are capable of supporting multiple cycles of HDT. However, we were
      unable to acquire sufficient CD34+ cells to perform this processing in 45%
      (13/29) of patients and further improvements in yield are required to overcome
      the modest delay in neutrophil and platelet recovery.

PMID- 12006210
TI  - CliniMACS CD34-selected cells to support multiple cycles of high-dose therapy.
AB  - BACKGROUND: Traditionally, following high-dose therapy (HDT), unmanipulated
      autologous PBPC are infused. Alternatively, purified CD34+ cells can now be
      obtained by immunomagnetic separation using the CliniMACS device. Limited data
      currently exist examining hemopoietic recovery with such cells. METHODS: Ten
      patients with advanced breast cancer had PBPC mobilized with docetaxel (100
      mg/m2) and G-CSF (10 microg/kg per day), harvested and processed using the
      CliniMACS CD34-selection device and equally divided into three aliquots for
      cryopreservation. Unmanipulated 'back-up' cells were also collected on a separate
      day of the same mobilization, divided into three and cryopreserved. Patients
      subsequently received three cycles of HDT with cyclophosphamide (4 g/m2),
      thiotepa (300 mg/m2) and paclitaxel (175 mg/m2). The intent was for patients to
      receive CD34-selected cells to support each of the three cycles of HDT (i.e., 1/3
      for each cycle). If, however, hemopoietic recovery was delayed after Cycle 1, 1/3
      of the unmanipulated cells were infused following Cycle 2 and the remaining CD34
      selected cells (2/3) were used to support Cycle 3. RESULTS: PBPC from 10 patients
      underwent CD34-selection with a resulting median purity of 93% (range: 76-98%)
      and yield of 62% (range: 16-93%). Of the 10 patients, only two were able to be
      supported with CD34-selected cells for all three cycles of HDT. The remaining
      eight patients required unmanipulated 'back-up' cells to support Cycle 2. Three
      patients also required infusion of 'back-up' unmanipulated cells because of
      persistent neutropenia (n = 1) or thrombocytopenia (n = 2) following cycles
      initially supported by CD34-selected cells. The median number of CD34-selected
      cells (x 10(6)/kg) infused per cycle was 1.5 (0.7-2.6) (n = 20) and unselected
      cells was 1.7 (1.4-2.8) (n = 10). Comparing hemopoietic recovery between cycles
      of HDT supported by CD34-selected (n = 20) and unmanipulated cells (n = 10) there
      was a significant slowing with the CD34-selected cells; time to ANC > 1.0 = 13
      days versus 10 days, platelets > 20 = 17 days versus 13 days, > 50 = 25 versus 17
      days (all P values < 0.001). There was no correlation between the dose of CD34
      selected cells infused and neutrophil/platelet recovery. DISCUSSION: We have
      demonstrated that, although unmanipulated PBPC achieve rapid hemopoietic recovery
      (at modest CD34 doses of < or = 2.8 x 10(6)/kg), CliniMACS-selected CD34+ cells
      (in the doses utilized in this study of < or = 2.6 x 10(6)/kg) result in
      significantly prolonged recovery.

PMID- 12006211
TI  - Viability of cryopreserved BM progenitor cells stored for more than a decade.
AB  - BACKGROUND: PBPC or BM is increasingly being harvested in remission for possible
      use in the event of relapse. Although the value of this approach has not been
      demonstrated, the long-term storage of progenitor cell components has become
      commonplace in many facilities. METHODS: We used multi-parameter flow cytometry
      to determine the viability of 11 long-term cryopreserved BM components (mean =
      11.8 years) in liquid phase nitrogen. The components, prepared for
      autotransplantation but deaccessioned after confirming patient death, were
      carefully thawed, washed, and assayed immediately. The flow cytometry assay was
      performed according to the ISHAGE protocol, modified by the addition of 7AAD for
      analysis of progenitor viability (CD45+ CD34+ 7AAD-) and total leukocyte
      viability (CD45+ 7AAD-). In addition, total viability was assessed by
      fluorescence microscopy using acridine orange dye exclusion; granulocyte-monocyte
      colony-forming units (CFU-GM) were measured after 14 days culture. RESULTS:
      Leukocyte viability by flow cytometry and fluorescence microscopy agreed well (r2
      = 0.55, slope = 0.83, P < 0.0005 by linear regression). CFU-GM did not correlate
      with CD34% or any of the viability parameters. Compared with short-term stored
      (mean = 33 days) PBPC assayed at infusion, long-term stored BM had a comparable
      percentage of CD34+ cells, comparable CFU-GM activity, increased CD34 viability,
      but decreased total cell viability, the latter most likely due to an increased
      proportion of differentiated myeloid cells. DISCUSSION: The results indicate that
      BM products can be cryopreserved for more than a decade without apparent loss of
      progenitor activity, as measured by these laboratory surrogates. This agrees with
      clinical anecdotes describing successful engraftment with long-term stored BM,
      and argues that expiration dates cannot be set for cryopreserved hematopoietic
      stem-cell components stored in liquid phase nitrogen.

PMID- 12006212
TI  - Immune escape mechanisms of childhood ALL and a potential countering role for DC
      like leukemia cells.
AB  - BACKGROUND: Pre-B ALL cells generally elicit a weak immune host response, due to
      poor expression of co-stimulatory molecules and/or suppression of immune
      function. A possible way to enhance immunogenicity of pre-B ALL cells is to
      convert them to DC-like cells. METHODS: To study the effect of ALL cells on T
      cell function, ALL cells were incubated with T adult cells activated by OKT3 MAb.
      Liquid culture of de novo pre-B ALL cells for 7 days, in a medium containing IL
      1alpha, IL-3, IL-7, Flt 3 ligand (L) and tumor-necrosis factor alpha (TNF-alpha)
      produced DC-like cells. These were evaluated for morphology, viability,
      phenotype, as measured by flow cytometry, and function, including MLR. RESULTS:
      Pre-B ALL cell-lines NALM-6, BALM and de novo pre-B ALL cells failed to stimulate
      T cells, but suppressed stimulated T cells. The DC-like cells displayed
      characteristic features of DCs: filiform cytoplasmic projections, and phenotypic
      expression of co-stimulatory molecules CD80/86, MHC Class I and II molecules,
      CD83 and CD1a. Genetic monoclonality study confirmed their leukemic origin. In a
      5-day MLR culture, the DC-like cells potently activated allogeneic adult and cord
      CD4+ and CD8+ T cells. Furthermore, both CD4+ and CD8+ T cells were primed
      towards a Type I. No such effect was seen with unmanipulated de novo pre-B ALL
      cells. DISCUSSION: DC-like cells can be generated from childhood pre-B ALL cells
      and are potent stimulators of adult and naive cord CD8+ T cells via CD4+ cells.
      These cells may form part of an immunotherapy strategy to overcome tolerance to
      ALL cells.

PMID- 12006213
TI  - Use of selected CD34+ cells in the treatment of relapsed/progressive HD:
      experiences from a single center.
AB  - BACKGROUND: Treatment of HD using positively selected stem cells can achieve a
      durable CR in almost 80% patients, with a median follow-up of 24 months. We have
      found the use of positive selected CD34+ cells in the treatment of
      relapsed/progressive HD after high-dose chemotherapy to be a safe procedure with
      promising results. METHODS: Positively selected (CD34+) stem cells were employed
      for autografting in the patients with HD after high-dose chemotherapy. RESULTS:
      Between April 1996 and February 2001, 28 patients with relapsed/progressive HD
      were autografted with positively selected CD34+ cells at our Institute. All
      patients are alive and we did not observe any deaths as a result of toxicity.
      From this group, 22 (78.6%) patients are in durable CR, with a median follow-up
      of 24 months (range 7-65 months). Six (21.4%) patients relapsed but are now in CR
      after radiotherapy and mini-allogeneic transplantation (one patient) or
      radiotherapy (five patients). DISCUSSION: Autologous transplantation with
      positively selected CD34+ cells in relapsed HD is a safe and effective procedure
      in the treatment of this disease.

PMID- 12006214
TI  - New laboratory tests in acute pancreatitis.
AB  - Acute pancreatitis (AP) is a common disease with wide variation of severity. The
      diagnosis of AP is usually based on high serum amylase or lipase values but the
      accuracy of these methods is considered unsatisfactory. One in five of the
      patients develops a severe disease and carries a considerable risk of development
      of organ failure and high mortality. Early detection of patients with severe AP
      and especially those with increased risk of organ failure is importance since
      such patients seem to benefit from treatment in an intensive care unit started as
      soon as possible after presentation. In addition to enzymological methods,
      increasing interest has been focused on laboratory markers reflecting the level
      of inflammatory response in AP. At present, in routine clinical work the most
      commonly used severity marker is serum C-reactive protein, the concentration of
      which rises too slowly to be used for early prediction of severity. New therapies
      aiming at modifying the course of systemic inflammation in AP are being developed
      and therefore monitoring the patient's immune inflammatory status is needed. In
      this review article we present the current knowledge of laboratory tests, which
      has been evaluated for diagnostic and prognostic purposes in AP.

PMID- 12006215
TI  - Alcohol exposure and paracetamol-induced hepatotoxicity.
AB  - Most instances of hepatotoxicity due to paracetamol in the United Kingdom and
      Australia are the result of large overdoses of the drug taken with suicidal or
      parasuicidal intent. In contrast, serious hepatotoxicity at recommended or near
      recommended doses for therapeutic purposes has been reported, mainly from the
      United States and in association with chronic alcohol use, leading to the widely
      held belief that chronic alcoholics are predisposed to paracetamol-related
      toxicity at relatively low doses. Yet the effects of alcohol on paracetamol
      metabolism are complex. Studies performed in both experimental animals and humans
      indicate that chronic alcohol use leads to a short-term, two- to threefold
      increase in hepatic content of cytochrome P4502E1, the major isoform responsible
      for the generation of the toxic metabolite from paracetamol, although increased
      oxidative metabolism of paracetamol at recommended doses has not been
      demonstrated clinically. A reduced hepatic content of glutathione, required to
      detoxify the reactive metabolite, has been documented in chronic alcoholics, due
      probably to associated fasting and malnutrition, providing a metabolic basis for
      any possible predisposition of this group to hepatotoxicity at relatively low
      paracetamol doses. Simultaneous alcohol and paracetamol ingestion reduces
      oxidative metabolism of paracetamol in both rodents and humans, predominantly as
      a consequence of depletion in cytosol of free NADPH. The possibilities that
      chronic alcohol use may predispose to paracetamol-related hepatotoxicity and that
      alcohol taken with paracetamol may protect against it, based on these metabolic
      observations, are examined in this review.

PMID- 12006216
TI  - Changes in mu opioid receptors and rheological properties of erythrocytes among
      opioid abusers.
AB  - Opioids, reported originally to bind to specific receptors in the brain, now also
      appear to bind to receptors on blood cells. The high prevalence of anemia among
      chronic opioid users leads us to propose that chronic opiate use results in
      elevated mu opioid receptor levels on human erythrocytes and that these receptor
      changes may affect erythrocyte membrane properties. Blood samples from 17 opioid
      dependent subjects (based on the Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition or DSM-IV) and 15 drug-free controls were assayed for mu
      opioid receptors on erythrocytes using a flow cytometry immunoassay.
      Deformability and the hydration status of erythrocytes were studied by
      ektacytometry. Data were analyzed by independent t-tests, tests of correlation,
      chi square and cluster analyses. As expected, the percentage of erythrocytes from
      opioid-dependent subjects with opioid receptors (opioid receptor levels) was
      significantly higher (47.4 +/- 38.3%) than controls (22.8 +/- 30.1%) (t = 2.01,
      df = 30, p < 0.05). Also, the opioid-dependent patients showed a wide variation
      in the percentage of erythrocytes bearing opioid receptors and data analyses of
      these patients showed two strongly defined clusters. One subgroup consisted of
      nine individuals with very high receptor levels (mean = 81.5%) while the other
      had eight patients with low receptor levels (mean = 9.1%) that were not
      significantly different than the receptor levels of controls. Ektacytometry of
      opioid dependent patients with high opioid receptor levels showed changes in
      rheological parameters of erythrocytes, such as deformability index and cellular
      hydration. For example, a positive correlation was observed between opioid
      receptor levels and deformability indices among opioid-dependent patients (r =
      0.74, p < 0.005). Our findings indicate that the mu opioid receptor is present on
      human erythrocytes, although with considerable variation in receptor levels, and
      that the levels of this receptor are significantly elevated with chronic opioid
      exposure. Moreover, erythrocytes with high opioid receptor levels from chronic
      opiate users seem to have high deformability. This study may offer clues to the
      biological properties of peripheral blood cells that may be mediated by mu opioid
      receptors and lead to a better understanding of some of the clinical effects of
      opioid use.

PMID- 12006217
TI  - In vivo and in vitro potency studies of 6beta-naltrexol, the major human
      metabolite of naltrexone.
AB  - Naltrexone, a mu opioid receptor antagonist, is used in the treatment of opioid
      and alcohol dependence. Naltrexone's longer duration of action compared to
      naloxone has been considered to be due partly to its major human metabolite,
      6beta-naltrexol. To date, no studies have examined the in vitro or in vivo
      potency of 6beta-naltrexol compared to naltrexone and naloxone. In the
      electrically-stimulated guinea pig ileum, 6beta-naltrexol was more potent (K(i) =
      94 +/- 25 pM), than naloxone (420 +/- 150 pM), and naltrexone (265 +/- 101 pM).
      In vivo comparative potencies were assessed using the mouse hotplate test and
      morphine (agonist), with doses of the antagonists from 0.001 to 30 mg/kg. The
      order of potency was naltrexone (ID(50) 7 microg/kg), naloxone (ID(50) 16
      microg/kg) and 6beta-naltrexol (ID(50) 1300 microg/kg). Antagonist ID(50) doses
      were then administered at 45, 90, 120, 180 and 1080 minutes prior to morphine
      administration. The duration of antagonist activity to decrease by 50% was 80,
      125 and 340 minutes for naltrexone, naloxone and 6beta-naltrexol, respectively.
      6beta-naltrexol is highly potent in the guinea pig ileum, but much less so in
      vivo after an acute dose. However, the potency of 6beta-naltrexol in vivo is time
      dependent, and it has a longer duration of action than naloxone and naltrexone,
      consistent with a pharmacokinetic longer terminal half-life. Therefore, 6beta
      naltrexol is likely to contribute to the efficacy of naltrexone in humans.

PMID- 12006218
TI  - Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic
      patients.
AB  - Apolipoprotein E epsilon4 and ACE genes have been related to several conditions
      involving cognitive impairment, including Alzheimer's disease, normal ageing and
      cerebrovascular disease. However, it has not been established whether their
      genotypes are associated with alcoholism or its cognitive functioning. Genotypic
      distributions of 140 chronic alcoholic patients were compared with a non
      alcoholic sample, and the cognitive performance of a subsample of the alcoholic
      subjects was assessed with standard neuropsychological tests. No differences in
      allele or genotype distributions of Apo E or ACE genes were found when comparing
      controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06;
      epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4;
      patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72%
      p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36;
      epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%,
      controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I;
      patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance,
      epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual
      memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore,
      ACE D/D patients performed better on a test of abstract reasoning (p < 0.03)
      compared with the ACE I/I homozygous group. The cognitive results suggest that
      Apo E or ACE genotypes may modify the effects of ethanol on cognitive
      deterioration in alcoholic patients. However, the data do not support an
      association between the Apo E epsilon4 allele and reduced cognitive performance
      in alcoholism.

PMID- 12006219
TI  - Tuberculin skin testing in intravenous drug users: differences between HIV
      seropositive and HIV-seronegative subjects.
AB  - The prevalence of tuberculin skin test reactions among intravenous drug abusers
      and differences in tuberculin skin test positivity between HIV-seropositive and
      HIV-seronegative subjects were evaluated in a cross-sectional study of 1131
      subjects. They were recruited from a therapeutic community, from those who
      attended the centre for the treatment of drug addiction and from those who
      visited for any reason an acute tertiary-care hospital in Vitoria-Gasteiz, Basque
      Country (Spain). All subjects underwent skin testing with purified protein
      derivative (PPD) tuberculin and testing for HIV antibodies. CD4(+) T-lymphocyte
      count was determined in HIV-seropositive individuals. Positive PPD tests were
      recorded in 35% of drug users who were HIV-seropositive and in 65% in those who
      were HIV-seronegative. In the HIV-infected group, there was a significant
      association between results of the tuberculin test and CD4(+) T-lymphocyte count.
      When the CD4(+) T-lymphocyte count was > or = 500 cells/mm(3), percentages of
      positive PPD tests were similar in HIV-seropositives and HIV-seronegatives (47%
      versus 65%) but when the CD4(+) count was < 500 cells/mm(3), positive PPD tests
      occurred in only 21% of HIV-seropositives. The PPD test showed a decreased
      sensitivity for detecting tuberculosis infection in HIV-infected intravenous drug
      users with CD4(+) T-lymphocyte counts fewer than 500 cells/mm(3).

PMID- 12006220
TI  - 24-Hour opiate detoxification and antagonist induction at home--the 'Asturian
      method': a report on 1368 procedures.
AB  - The technique of domiciliary rapid opiate detoxification (ROD) developed in
      Asturias since 1994 enables patients dependent on heroin and/or methadone (or
      other opiates) to start antagonist maintenance with a full dose of naltrexone (50
      mg) and largely recover from the acute opiate withdrawal syndrome in a few hours
      at home without direct medical or nursing involvement. Detailed information on
      1368 procedures is presented but in Asturias, over 3000 procedures have been
      completed to date without any deaths or serious medical or psychiatric
      complications. We also describe some recent modifications to the procedure
      involving the use of octreotide as an antidiarrhoeal and the insertion of
      subcutaneous naltrexone implants to prevent early relapse. Rather than
      domiciliary ROD, we think the procedure is more usefully conceptualized as
      domiciliary rapid antagonist induction (RAI), because treatment with well
      supervised naltrexone is known to be effective in reducing relapse rates. Now
      that controlled studies uniformly describe greatly increased rates of transfer to
      naltrexone maintenance treatment following RAI, compared with conventional slower
      withdrawal and naltrexone induction procedures, it is important that the safety,
      acceptability and simplicity of this 'Asturian' RAI/ROD technique become more
      widely known.

PMID- 12006221
TI  - Distinct effects of paradoxical sleep deprivation and cocaine administration on
      sexual behavior in male rats.
AB  - As there are data showing enhanced sexual activity in paradoxical sleep deprived
      (PSD) rats, and cocaine (COC) is a drug of abuse known to also increase the
      sexual drive, the present study aimed to assess sexual behavior in animals
      submitted to PSD and/or COC administration. The data revealed that PSD followed
      by COC administration produced the largest percentage of animals having erection
      and ejaculation (100% and 60%) and differ statistically from the control groups.
      The PSD group that received saline produced 50% erections and 20% ejaculations
      whereas COC administration induced 10% erections and 10% ejaculations. Sexual
      activity was absent in control animals (saline injection). These findings are due
      probably to PSD causing supersensitivity of dopamine (DA) receptors exacerbating
      the cocaine actions on dopaminergic pathways inducing penile erection and
      ejaculation.

PMID- 12006223
TI  - Future End-of-Life Care: Best Ideas, Practices, & Policies. Proceedings of the
      W.K. Kellogg Foundation National Leadership CGA Seminar. Warrenton, VA, USA.
      November 17-20, 2001.

PMID- 12006222
TI  - Effects of cigarette smoking with different tar content on erythrocyte
      oxidant/antioxidant status.
AB  - In this study, the effects of cigarettes with differing tar content on
      erythrocyte oxidant/antioxidant status was investigated. Malondialdehyde (MDA) as
      an indicator of oxidant status and superoxide radical scavenger activity (SSA) as
      an indicator of antioxidant status were measured in erythrocytes from 20 smokers
      and 10 non-smoker controls. Ten of the 20 smoking subjects smoked five cigarettes
      with full flavour low tar (FFLT with 12 mg tar) and the others smoked five
      cigarettes with full flavour high tar (FF with 23 mg tar) over 1 hour. Initial
      blood samples from both groups at fasting, followed by further samples from
      smokers at 1.5 hours and 3 hours after smoking. Initial erythrocyte MDA level and
      SSA activity were found to be higher in the smoking groups compared to non
      smokers. Furthermore, both parameters were significantly higher at the 1.5-hour
      and 3-hour erythrocyte samples when compared to initial values in the FFLT group.
      However, there were no statistically significant differences between SSA values
      established at different times in FF group. Results suggest that smoking causes
      oxidant load in the erythrocytes. Although a compensatory mechanism (i.e.
      increased SSA activities) develops in the FFLT group after smoking, this cannot
      prevent peroxidation reactions (i.e. increased MDA levels) in the erythrocytes.
      As to the types of cigarettes, both seem to have oxidant potential, but oxidation
      degree in the FFLT group is higher than that of FF group. These results suggest
      that antioxidant supplementation to smokers might be beneficial to decrease
      cellular oxidation damages.

PMID- 12006224
TI  - Medical education in end-of-life care: the status of reform.
AB  - Deficiencies in education about end-of-life care are widely recognized, both in
      the "formal" or structured curriculum, and in the "informal" curriculum (the
      culture in which students are immersed as they learn medicine). Numerous
      approaches to addressing these deficiencies have been identified. These
      approaches include developing palliative care leaders; improving curricula;
      creating standards and a process for certification of competence; creating and
      enhancing educational resources for end-of-life education; faculty development;
      growing palliative care clinical programs as venues for education; textbook
      revision; and creating palliative care fellowship training opportunities. Current
      efforts in these areas are reviewed, and barriers to their implementation are
      highlighted.

PMID- 12006225
TI  - The medical futility debate: patient choice, physician obligation, and end-of
      life care.
AB  - Physicians' use of the "medical futility" concept to override the treatment
      demands of patients or their family/surrogates is difficult to justify in
      principle. At the same time, patient demands for obviously futile treatments can
      conflict with physicians' professional obligation to do no harm to their
      patients. There is no clear general principle available to resolve this conflict
      between patient self-determination and physician autonomy; extended negotiation
      between patient or family/surrogates and physicians provides the only prospect
      for satisfactory resolution. Though such negotiation will not invariably succeed
      in reaching agreement, the legal system should ensure that each side has some
      practical measure of independent authority and power to exert against the other
      in order to maximize the likelihood that the negotiating process will be
      seriously engaged.

PMID- 12006226
TI  - Systems of care: future reform.
AB  - Major new ideas and opportunities shape the direction of reform in serving those
      coming to the end of life. Framing the problems as arising from changing
      demographics and evaluation of how we envision categories seems better than past
      ways of framing the issues. Another useful strategy is to build programs around
      three trajectories of the time course of disability while dying: a confined
      period of rapidly progressive disability and symptoms; intermittent exacerbations
      against the background of substantial organ system failure; and extreme
      multifactorial frailty. Finally, reform requires quality improvement,
      restructuring, and changes in Medicare payment.

PMID- 12006227
TI  - Hospice and future of end-of-life care: approaches and funding ideas.
AB  - To increase the number of people using hospice and the length of stay in
      hospices, the hospice movement needs more urgently to refocus its message than to
      make the benefit more attractive.

PMID- 12006228
TI  - Future of end-of-life care: the managed care organization perspective.

PMID- 12006230
TI  - The meaning and value of death.

PMID- 12006229
TI  - The role of hospice care in the nursing home setting.
AB  - The last days of life for a substantial proportion of dying older adults are
      spent in nursing homes. Considering this, the provision of Medicare hospice care
      in nursing homes would appear to be an equitable use of Medicare expenditures as
      well as a valid investment in improving the quality of life for dying nursing
      home residents. However, government concerns regarding possible abuse of the
      hospice benefit in nursing homes, as well as suggestion that the payment for the
      benefit in nursing homes may be excessive, has perhaps slowed the adoption of
      hospice services into the nursing home setting. Currently, access to hospice care
      in nursing homes is inequitable across facilities, and across geographic areas.
      In nursing homes where hospice is available and present, however, recent research
      documents superior outcomes for residents enrolled in hospice, and perhaps for
      nonhospice residents. Still, more research is needed, particularly research
      focusing on the government costs associated with the provision of hospice care in
      nursing homes. If subsequent research continues to support the "added value" of
      hospice care in nursing homes and at the same or less total costs, the issue of
      foremost concern becomes how equitable access to Medicare hospice care in nursing
      homes can be achieved. Access may be increased to some extent by changing
      government policies, and conflicting regulations and interpretive guidelines, so
      they support and encourage the nursing home/hospice collaboration.

PMID- 12006231
TI  - Spirituality and end-of-life care: a time for listening and caring.

PMID- 12006232
TI  - Vicissitudes of the clinician-patient relationship in end-of-life care:
      recognizing the role for teams.

PMID- 12006233
TI  - Redefining symptom management.

PMID- 12006234
TI  - Changing end-of-life planning: the Oregon experience.
AB  - Large state-by-state variations exist in location of dying and level of
      aggressive treatment during the final phase of life. This paper describes
      Oregon's incremental gains toward improving advance planning for end-of-life care
      in a state with the lowest rate of in-hospital deaths. Action strategies have
      required data gathering and reporting, and coalition building with a focus on
      systems change. Also, public education through the news media has proved to be a
      vital component of Oregon's process of change. The impact of media coverage is
      complemented by continuing education for health professionals. Special efforts
      are still needed to improve access to the Physician's Orders for Life-Sustaining
      Treatment program (POLST) for some rural, minority, and pediatric populations and
      for persons living at home with a diagnosis other than cancer. However, with
      enough time, a sustained effort, and a broad coalition of partners, profound
      change is possible.

PMID- 12006235
TI  - Palliative care models: international perspective.
AB  - The delivery of palliative care can vary greatly between countries depending on
      socioeconomic conditions and cultural issues. The evolution and development of
      palliative care varies greatly and influences the development of palliative care
      models. Models of palliative care in three different countries are discussed and
      suggestions are made for the future development of palliative care in developing
      and developed countries.

PMID- 12006236
TI  - Future end-of-life care: partnership and advocacy.

PMID- 12006237
TI  - Introduction--translational research trends: urologic gene therapy.

PMID- 12006238
TI  - Status and prospects of gene therapy for urologic cancer.

PMID- 12006239
TI  - Gene therapy as translational research.

PMID- 12006240
TI  - Ex vivo gene therapy using granulocyte-macrophage colony-stimulating factor
      transduced tumor vaccines.
AB  - There is no standard effective therapy for metastatic renal-cell carcinoma (RCC)
      or prostate cancer. Both of these cancers may be immunogenic, so therapy targeted
      to a tumor-associated antigen may be effective. Transduction of the gene encoding
      granulocyte-macrophage colony-stimulating factor has shown promise in preclinical
      studies, and clinical trials are in their early stages. Both autologous cancer
      cells and partially HLA-matched allogenic cells are being studied. No dose
      limiting side effects have been observed, and a few patients have had transient
      objective tumor regressions. Further trials with more frequent and, probably,
      longer immunization schedules are needed to define efficacy.

PMID- 12006241
TI  - Cytokine gene therapy for cancer with naked DNA.
AB  - Plasmid DNA vectors (naked DNA) can easily be purified and transferred in vivo by
      intramuscular or intradermal injection. Naked DNA is stable in vivo, and long
      term expression of the encoded protein is seen without chromosomal integration.
      Gene gun-mediated delivery of an expression plasmid is slightly more complicated
      but more efficient. These techniques have been applied to DNA vaccination or
      cytokine gene therapy for various diseases, including infections, autoimmune
      disorders, and cancer. We review cytokine gene therapy for cancer with naked DNA
      in animal models and present our preliminary data on gene gun-mediated in vivo
      transfection with the interleukin-12 gene in a murine renal cancer model. Because
      of its safety, simplicity, and low cost, cytokine gene therapy with naked DNA may
      become an important cancer treatment.

PMID- 12006242
TI  - Adenovirus-mediated p53 gene therapy for human cancer.
AB  - Recent advances in molecular biology have fostered remarkable insights into the
      molecular basis of neoplasms. Considerable evidence has accumulated that among
      the mechanisms of human cancer development are overexpression of dominant
      oncogenes, expression of mutant oncogenes, or specific chromosomal deletions or
      mutations that induce inactivation of tumor-suppressor genes. This understanding
      of cancer pathogenesis suggests that restoration of the function of critical gene
      products could halt or reverse these abnormalities, thus having a therapeutic
      effect. The p53 tumor suppressor gene has been implicated in many inherited and
      sporadic forms of malignancies in humans. Preclinical experiments have
      demonstrated that restoration of wildtype p53 function in the cancer cell by gene
      transfer is sufficient to cause antitumor effects such as cell-cycle arrest and
      induction of apoptosis. This approach has entered clinical testing and provided
      intriguing information about the intratumoral administration of an adenovirus
      vector expressing the wildtype p53 gene in non-small-cell lung cancer. The
      clinical study has also provided evidence of the bystander phenomenon, which is
      important for potential clinical efficacy. This article reviews recent highlights
      in this rapidly evolving field: p53 gene therapy for human cancer.

PMID- 12006243
TI  - Application of antisense technology to urologic cancers.
AB  - Antisense oligodeoxynucleotides (ODNs) inhibit target gene expression and are
      applicable to human diseases including malignancies. Although improvements in
      ODNs and cellular delivery systems are needed, antisense ODNs hold great promise
      as a new class of therapeutic agents.

PMID- 12006244
TI  - Hammerhead ribozymes as therapeutic agents for bladder cancer.
AB  - Hammerhead ribozymes have been investigated extensively as therapeutic agents
      against cancer. Aberrant or overexpression of genes related to tumorigenicity or
      cancer growth might be the appropriate targets for ribozyme strategies. Ribozyme
      mediated gene therapy should be applied to those diseases that have no successful
      conventional therapy such as advanced or treatment-resistant bladder cancer. Many
      genetic alterations have been identified in bladder cancer related to both
      tumorigenesis and disease progression. Mutated H-ras, fos, and erb-B2 genes have
      been chosen as targets for ribozymes in previous studies, and antitumor efficacy
      has been demonstrated by reversion of the malignant phenotypes and by inhibition
      of tumor growth both in vitro and in vivo. The efficiency of various delivery
      systems has also been evaluated. An overview of ribozyme strategies, especially
      for therapeutic applications against bladder cancer, is described here.

PMID- 12006245
TI  - Suicide gene therapy for urogenital cancer: current outcome and prospects.
AB  - Viral-mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk)
      gene has been demonstrated by several investigators to confer sensitivity to
      nucleoside analogs such as ganciclovir (GCV) in a variety of tumor cells
      including brain, prostate, bladder, kidney, ovary, head and neck, lung, pancreas,
      and liver cancers. Fourteen suicide gene clinical protocols using adenovirus
      vectors have been conducted, including four in prostate cancer. Two additional
      protocols for prostate cancer are in preparation in Japan and the Netherlands. A
      study conducted at Baylor College of Medicine was the first to demonstrate the
      safety of HSV-tk plus GCV therapy for human prostate cancer and the anticancer
      activity of gene therapy in this disease. However, it is still in the early stage
      of its development, with a number of problems to be overcome. Systemic delivery,
      specific introduction, and specific expression of the target gene are the major
      issues to be managed in order to establish a clinically relevant treatment
      strategy.

PMID- 12006246
TI  - Tissue-specific promoters in gene therapy for the treatment of prostate cancer.
AB  - Delivery of therapeutic toxic genes to and their expression in tumor cells
      through the use of tissue-specific promoters could decrease their toxic effect on
      neighboring normal cells when virus-mediated gene delivery results in their
      infection. We have demonstrated the utility of two prostate cancer-specific
      promoters, long PSA and osteocalcin, for tissue-specific toxic gene therapy for
      prostate cancer. The two promoters were highly active in both androgen-dependent
      and androgen-independent prostate cancer cells. We also introduce the Phase I
      trial of osteocalcin promoter-based toxic gene therapy for bone metastases of
      prostate cancer, which is in progress at the University of Virginia.

PMID- 12006247
TI  - Application of conditionally replicating herpes vector for gene therapy treatment
      of urologic neoplasms.
AB  - Herpes vector has been widely used for experimental gene therapy. We herein
      review the strategies of such therapy for the treatment of urologic neoplasms.
      Most experimental studies of genetically altered viruses have employed
      replication-incompetent vectors. However, such viruses are unable to infect
      additional cells subsequent to the initial infection event. Therefore, this
      strategy has relied heavily on the bystander effect because a large number of
      noninfected tumor cells remain. Conditionally replicating herpes vector G207 has
      been developed in order to overcome potential problems of safety and tumor
      specificity for human use. It has been used to treat malignant brain tumors
      because of its neural tropism. In the last few years, applications of G207 for
      non-neural tumors have been reported. Because G207 may be useful for the
      treatment of urologic malignant tumors, we evaluated the antitumor effect against
      several types of tumor cells both in vitro and in vivo. Our data suggest that
      G207 may be applicable for the treatment of urologic malignant tumors.

PMID- 12006248
TI  - [SEEIUC].

PMID- 12006249
TI  - [Sexuality in acute myocardial infarction patients].
AB  - We as nurses in the Coronary Unit we do not see the sexuality of the patients
      sufficiently addressed neither by us nor by the patients themselves. In this
      article we are trying to analize the reasons and to emphasize the need to include
      this subject in our Nursing Problem List. In it we explaine the fears and the
      wrong ideas that we have identified in our patients. The sexual function is not
      affected by a myocardial infarction but psychological factors, age, drugs and
      other associated diseases might be a reason. A quiet enviroment, a fit training
      plan and looking for personalise proper alternatives may help the patient to
      start a satisfactory sexual life again.

PMID- 12006250
TI  - [Burnout's syndrome in critical care nursing professionals].
AB  - The concept of the "Burnout Syndrome" has come as a result of the chronic work
      stress developed in workers involved in human services during their professional
      activity. The working conditions and the specific characteristics of the job
      developed at the Intensive Care Units by the nursing staff, involve a high risk
      for this group to acquire this syndrome. The main objective of this study is to
      assess the prevalence of the Burnout Syndrome in the nursing staff of the ICUs in
      different hospitals of the Alicante province, Spain, by means of the Malsach
      Burnout Inventory questionnaire. This questionnaire is self-administered and was
      handed to all the nursing staff at the ICUs in the University Hospitals of
      Alicante and Elche and in the Hospital Marina Baixa of Villajoyosa. form the
      total of 107 questionnaires, 83 proved to be valid. The average total of MBI was
      of 55.05, indicating low values of emotional tiredness, low depersonalisation,
      and an adequate level of personal accomplishment.

PMID- 12006251
TI  - [Creation of the World Federation of Critical Care Nursing (WFCCN)].

PMID- 12006252
TI  - [Some thonghts over the visits to the intensive care units].

PMID- 12006254
TI  - [Has a decade of standardizing antifungal sensitivity tests accomplished
      anything?].

PMID- 12006255
TI  - [Incidence of colonization and infection by Acinetobacter baumannii in an endemic
      seting (ICU). Analysis of risk factors by means of a surveillance study].
AB  - BACKGROUND: Our ICU has witnessed a gradual increase in infections due to
      Acinetobacter baumannii complex that has reached a level of stable endemia since
      1995. This situation, aggravated by a high degree of resistance, has led to the
      present prospective study, designed to establish the incidence of Acinetobacter
      colonization and to investigate the role of risk factors and their relation to
      environmental colonization. METHODS: Serial sampling of all patients from the
      time of ICU admission to discharge. Sample collection from the environment and
      from hospital personnel. Monitorization of pre-established risk factors and
      detection of episodes of infection. RESULTS: One-third of patients were colonized
      during their stay, with the trachea (43%), rectum (31%), and skin (35%) being the
      most frequent sites. In 92% of cases, colonization was established within the
      first 9 days after admission. Significant risk factors included mechanical
      ventilation (p < 0.01) and previous use of antibiotics (p < 0.007). Acinetobacter
      was recovered from thermometers (35%), respirator switches (43%), and damp
      surfaces (54%). Infection developed in 8% of patients; all had been previously
      colonized. CONCLUSIONS: In an endemic setting, Acinetobacter colonization can
      occur in a third of ICU patients. This event is relatively early and often
      precedes infection. Duration of mechanical ventilation and previous use of
      antibiotics are the main risk factors. Environmental elements are frequent
      bacterial reservoirs, but the main reservoir is the colonized patient.

PMID- 12006256
TI  - [Prevalence of hepatitis C virus genotypes in the area of El Ferrol (La Coruna,
      Spain)].
AB  - BACKGROUND: To determine the prevalence of hepatitis C virus (HCV) genotypes in
      the area of El Ferrol, as well as their distribution according to risk factors.
      METHODS: A total of 479 patients with hepatitis C were studied, including 254
      with no known risk factors, 161 intravenous drug abusers (IVDA) and 64 with a
      history of blood transfusions. The presence of HCV RNA was studied by RT-PCR, and
      a reverse hybridization method (INNO-LiPA) was used for genotyping. RESULTS:
      Genotype distribution was as follows: 1b, 269 (56.2%); 1a, 79 (16.5%); 3a, 59
      (12.3%); 4c/4d, 35 (7.3%); 1, 19 (4.0%); 2a/2c, 3 (0.6%); 4, 3 (0.6%); 2b, 2
      (0.4%). In 10 patients (2.1%) genotype could not be determined. In patients with
      no known risk factor, the predominant genotype was 1b, detected in 191 of the 254
      patients in this group (75.2%). Distribution of genotypes was more varied in the
      IVDA group, with the most frequent being 1a in 49 (30.4%) and 3a in 43 (26.7%).
      In the 64 patients who had received transfusions, 1b was predominant, detected in
      54 of 64 patients (84.4%). CONCLUSIONS: The predominant HCV genotype in our area
      is 1b. Differences in genotype distribution were observed in the population
      groups studied, according to their underlying risk factors.

PMID- 12006257
TI  - [Prevalence of Chlamydia trachomatis infection, as evaluated by molecular biology
      methods].
AB  - BACKGROUND: To determine the prevalence of Chlamydia trachomatis infection in our
      area by molecular methods. METHODS: We describe the combined results of three
      studies carried out in the city of Barcelona including a total of 408 women
      considered to be at high risk for acquiring a sexually transmitted disease (STD).
      The first study was performed in 94 women attended at a public STD clinic located
      downtown, the second in 112 women attended at the Hospital Clinic and the third
      in 202 women attended at Hospital Vall d'Hebron (both third-level hospitals). In
      the first and third study endocervical exudate was tested with a PCR technique,
      and in the second study LCR was performed in 20-ml urine samples. RESULTS:
      Chlamydia trachomatis was detected in 1 woman in the first study, in no women in
      the second and in 3 women in the third. The prevalence of Chlamydia trachomatis
      infection detected in the three studies using molecular biology techniques was
      1.06%, 0% and 1.48% respectively, giving an overall prevalence of 0.98%.
      CONCLUSION: The prevalence of Chlamydia trachomatis infection in our geographic
      area is surprisingly low.

PMID- 12006258
TI  - [Salmonella spp. serotypes isolated at the Hospital Universitario Reina Sofia in
      Cordoba during an 8-year period, 1993-2000].
AB  - BACKGROUND: As a producer of gastro-enteritis and other symptoms, Salmonella spp.
      Remains an important problem for world public health. Epidemiological knowledge
      at both general and local level by means of serotypification is considered one of
      the fundamental aspects for its control. MATERIAL AND METHOD: We studied 15.181
      stool samples, and the others specimens. Isolation using the usual routine media,
      agar MacConkey, Salmonella-Shigella, selenito F. Identification using the
      automated Microscan and wider I method, serotypification with multi-purpose and
      monospecific serums (Difco), and confirmation of Salmonella and Shigella by the
      National Reference Laboratory, from the LNRSSE. RESULTS: Although 96.6% of
      Salmonella spp. Is detected in cultures of faeces and blood, it is also noted in
      LCR, sputum, rectal biopsy and vaginal secretions among other sites. In total of
      1290 patients, 37 different serotypes were isolated, the most frequent of which
      were Enteritidis and Typhimurium. The presence of Virchow, isolated in both
      faeces and LCR, was notable in the years 94-99, as was as the presence of less
      typical serotypes, such as Blockley, London, Give and Mikawasima, among others.

PMID- 12006259
TI  - [Laboratory diagnosis of pertussis. Role of serology].
AB  - Culture is the reference method for the diagnosis of infection by Bordetella
      pertussis. Nevertheless, delayed sample collection and previous antibiotic
      treatment can limit culture sensitivity. In principle, direct immunofluorescence
      provides immediate diagnosis. It is, however, a subjective procedure that shows
      low sensitivity and specificity. PCR techniques increase culture sensitivity
      while maintaining high specificity, but their performance decreases along the
      evolution of the disease. Serologic methods are the main alternative for cases in
      which diagnosis is delayed. Current recommendations center on ELISA techniques
      that include purified antigens, such as filamentous hemaglutinin, and
      particularly, pertussis toxin. Traditionally, serological diagnosis requires
      confirmation by demonstrated seroconversion, but now the possibility of diagnosis
      based on titration of a single serum sample is being evaluated.

PMID- 12006260
TI  - [Diarrhea in an alcoholic patient].

PMID- 12006261
TI  - [Dermal lesion after a recent trip to Venezuela].

PMID- 12006262
TI  - [Tumoral lesion of the anterior chest wall in a patient with AIDS].

PMID- 12006263
TI  - [Interpretive reading of the antibiogram of enterobacteria].
AB  - Many of the resistance mechanisms of enterobacteria to antimicrobial agents are
      well understood; nevertheless several aspects remain unsolved, particularly with
      regard to prediction of clinical response. The resistance pattern observed in the
      antibiogram of a specific organism should be the sum of the natural resistance
      pattern, characteristic of the species, plus the acquired resistance. In
      enterobacteria the principal mechanism of resistance to beta lactams and
      aminoglycosides is enzyme production, Each enzyme recognizes one or more specific
      beta lactam or aminoglycoside, as a substrate. This translates as a specific
      resistance phenotype that allows one to infer the enzyme(s) implicated. Enzyme
      resistance is not, however, the only mechanism of resistance to these agents;
      often the pattern observed is multifactorial. Resistance to quinolones is due to
      point and sequence mutations which may be selected by initially active
      fluoroquinolones and cause a stepwise increase of resistance.

PMID- 12006264
TI  - [Abscess of the psoas muscle. Primary or secondary?].

PMID- 12006265
TI  - [Atypical presentation of Plesiomonas shigelloides infection].

PMID- 12006266
TI  - [Polyarticular septic arthritis due to Escherichia coli].

PMID- 12006267
TI  - [Use of quinolones in high level sports].

PMID- 12006268
TI  - [Isolation of maltose-negative Neisseria meningitidis from vaginal exudate].

PMID- 12006269
TI  - Leptomeningeal tumor: the "plain vanilla" approach remains the best.

PMID- 12006270
TI  - CT/MR perfusion imaging and alphabet soup: an appeal for standardized
      nomenclature.

PMID- 12006271
TI  - N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations:
      results of a prospective, randomized, multi-center trial.
AB  - BACKGROUND AND PURPOSE: Liquid N-butyl cyanoacrylate (n-BCA) use for the
      treatment of arteriovenous malformations (AVM) in the brain has become part of
      medical practice. However, no study has led to the Food and Drug Administration's
      approval of n-BCA for intravascular use. The purpose of this study was to verify
      the effectiveness and safety of an n-BCA/Tantalum Powder/Ethiodized Oil mixture,
      compared with conventional treatment (Trufill polyvinyl alcohol [PVA]) for
      preoperative embolization of cerebral AVM. METHODS: Between October 15, 1996, and
      March 24, 1999, 104 patients at 13 centers were prospectively randomized to
      undergo embolization using an n-BCA/Tantalum Powder/Ethiodol mixture or Trufill
      PVA. The pre-embolization therapy goals were determined in terms of the number of
      pedicles to be embolized and the percent of nidus reduction expected.
      Embolization results were evaluated by a central laboratory. Subsequent surgical
      resection data were recorded. Safety evaluation data included recording device
      complications, procedure complications, and intracranial events/overall
      neurologic outcomes, which could be either device-related, procedure-related, or
      both. RESULTS: The reduction of AVM dimensions (79.4% in the n-BCA group and
      86.9% in the PVA group) and the mean number of vessels embolized (2.2 in the n
      BCA group and 2.1 in the PVA group) was similar in the two groups. Coils were
      used more commonly with PVA embolization (P<.0001). No differences were detected
      in surgical resection time, number of patients who required transfusion, volume
      and number of transfusion units, or type and volume of fluid replacement. Glasgow
      Outcome Scale scores were not significantly different between the two groups
      before treatment, after embolization, or after resection. Two of 42 patients who
      underwent resection and had been treated with n-BCA experienced post-resection
      hematoma, compared with eight of 45 patients who underwent resection and had been
      treated with PVA (P<.05). CONCLUSION: This prospective, randomized trial showed
      that n-BCA is equivalent to PVA as a preoperative embolic agent for treatment of
      cerebral AVM as determined by percent of nidus reduction and number of feeding
      pedicles embolized.

PMID- 12006272
TI  - Endovascular treatment of unruptured intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Intracranial aneurysms are common, with an overall
      frequency ranging from 0.8% to 10%. Because prognosis after subarachnoid
      hemorrhage is still very poor, treatment of unruptured aneurysms, either
      neurosurgically or endovascularly, has been advocated. However, risk of rupture
      and subsequent subarachnoid hemorrhage needs to be considered against the risks
      of elective treatment. We analyzed the technical feasibility, safety, and
      efficacy of endovascular treatment of a consecutive series of unruptured cerebral
      aneurysms. METHODS: From July 1997 through December 2000, a total of 76 patients
      with 82 unruptured cerebral aneurysms were treated at our institution.
      Endovascular treatment was administered to 39 consecutive patients with a total
      of 42 unruptured cerebral aneurysms. Thirty-six aneurysms were treated with an
      endovascular technique; in six patients, the parent artery was occluded to
      eliminate aneurysmal perfusion. Aneurysms were located either in the anterior (n
      = 31) or posterior (n = 11) circulation. Eight patients had experienced previous
      subarachnoid hemorrhage from other aneurysms and were treated electively after
      complete rehabilitation. Ten patients had neurologic symptoms; in 21 patients,
      the aneurysm was an incidental finding. Eighteen aneurysms were small (0-5 mm),
      11 were medium (6-10 mm), nine were large (11-25 mm), and four were giant (> 25
      mm). Occlusion rate was categorized as complete (100%), subtotal (95-99%), and
      incomplete (< 95%) obliteration. RESULTS: Endovascular treatment was technically
      feasible for 38 of 42 aneurysms. Complete (100%) or nearly complete (95-99%)
      occlusion was achieved in 34 of 38 aneurysms. In four aneurysms of the internal
      carotid artery, only incomplete (< 95%) occlusion was achieved. All patients
      except one with mild neurologic deficits according to the Glasgow Outcome Scale
      and one with mild memory dysfunction but no focal neurologic deficit achieved
      good recovery, resulting in a morbidity rate of 4.8% and a mortality rate of 0%.
      CONCLUSION: Endovascular embolization of unruptured cerebral aneurysms is an
      effective therapeutic alternative to neurosurgical clipping and is associated
      with low morbidity and mortality rates. For the management of unruptured
      aneurysms, endovascular treatment should be considered.

PMID- 12006273
TI  - Evaluation of the stability of aneurysms after embolization using detachable
      coils: correlation between stability of aneurysms and embolized volume of
      aneurysms.
AB  - BACKGROUND AND PURPOSE: The long-term outcome of aneurysmal coil embolization has
      not been determined. We retrospectively analyzed the results of our cases treated
      with detachable coils and evaluated the long-term stability of embolized
      aneurysms. METHODS: This study involved 100 aneurysms in 93 patients who
      underwent follow-up angiography > or = 3 months after initial treatment between
      December 1993 and December 1999. The percentage of the coil volume occupying the
      aneurysm lumen (embolized volume) was used as an index to evaluate the stability
      of embolized aneurysms. The reliability of the embolized volume was also
      evaluated by comparing angiographic percentage occlusion. RESULTS: Follow-up
      angiographic assessment was conducted 12 +/- 8.5 months after initial treatment.
      Angiographic evaluation of percentage occlusion at initial treatment did not
      always predict long-term stability of embolized aneurysms. Of 49 aneurysms judged
      as being totally occluded at initial treatment, 44 remained unchanged and five
      showed recanalization. The embolized volume of unchanged aneurysms was 30.8 +/-
      10.2%, and that of recanalized aneurysms was 19.9 +/- 10.6%. There was a
      significant difference between these two groups (P=.03). Of 29 subtotally
      occluded aneurysms, nine had further thrombosis (embolized volume = 31.8 +/-
      12.7%), nine remained unchanged (embolized volume = 23.2 +/- 10.3%), and 11 had
      recanalization (embolized volume = 14.1 +/- 6.1%). The mean embolized volume of
      11 recanalized aneurysms was significantly lower than in the thrombosed group and
      the unchanged group (P=.002 and P <.001, respectively). Large aneurysms tended to
      have recanalization more frequently (59%) than did small aneurysms (15%).
      CONCLUSION: There is a significant correlation between embolized volume and
      stability of embolized aneurysms. Embolized volume is a more objective index than
      is subjectively angiographic percentage occlusion. In addition to angiographic
      assessment, measurement of embolized volume could be useful to predict
      angiographic changes of aneurysms.

PMID- 12006274
TI  - The learning curve for coil embolization of unruptured intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Several studies have shown that procedural outcomes are
      better at high-volume institutions, possibly due to greater physician experience
      (learning) or practice (repetition). Our purpose was to determine whether
      outcomes for coil embolization improved with the experience of the practitioner,
      after adjusting for the perceived risk of treatment. METHODS: We identified all
      unruptured aneurysms treated with coil embolization at our institution from 1990
      through 1997. A clinical nurse specialist abstracted the characteristics from
      cases that met the entry criteria. Two neurologists independently determined the
      complications by using definitions established a priori. The influence of
      experience of the treating-physician on complications was evaluated with
      univariate and multivariable logistic regression analyses. RESULTS: Sixteen
      complications occurred in 94 patients (17%) treated with coil embolization.
      Complications occurred in 53% of the first five cases that each of three
      physicians treated, and in 10% of later cases (P <.001). After an adjustment for
      all other predictors, including physician assessment of the risk of the
      procedure, the odds of a complication decreased with increasing physician
      experience (odds ratio, 0.69 for every five cases treated; 95% confidence
      interval: 0.50, 0.96; P=.03). CONCLUSION: The risk of complications with coil
      embolization of unruptured aneurysms appears to decrease dramatically with
      physician experience. Because the physicians in this study were highly
      experienced in other endovascular techniques at study onset, the rate of learning
      may not be generalizable to other centers.

PMID- 12006275
TI  - Quantitative assessment of polymerization-binding mechanics of cyanoacrylates:
      model development and validation.
AB  - BACKGROUND AND PURPOSE: Although commonly acknowledged as paramount in
      significance, the mechanics of cyanoacrylate polymerization remain poorly
      characterized and quantified for clinical applications. This prompted development
      of a simplistic model for the systematic study of polymerization and binding
      behaviors of cyanoacrylates. METHODS: A sliding bed apparatus was constructed
      that linked a strain gage with a vessel that could be filled with liquid medium,
      cyanoacrylate, and a microcatheter. As the cyanoacrylate polymerized, the
      microcatheter was mechanically drawn away very slowly from the fixed vessel,
      resulting in the development of forces that were recorded to characterize the
      dynamics of polymerization and binding. Optimization of the model required
      manipulation of several variables that could influence polymerization. Three
      different formulations of cyanoacrylate were also tested to determine whether
      there are significant differences in polymerization dynamics. RESULTS: After
      experimenting with a few basic physical parameters of the test apparatus,
      consistent measurements of binding forces during cyanoacrylate polymerization
      could be recorded and measured. Polymerization produced a multiphasic pattern of
      binding forces, in which three distinct phases were observed. Furthermore, the
      rates of polymerization were significantly influenced by a variety of parameters,
      including the type of fluid within the model vessel, geometry of the model
      vessel, and rate of injection of acrylic into the well. Furthermore, there were
      significant differences in the pattern of dynamic binding forces among the
      various formulations of cyanoacrylate tested. CONCLUSIONS: A standardized bench
      top testing apparatus has been developed, which can consistently show dynamic
      binding related to polymerization of cyanoacrylates. This preliminary study shows
      a clear multiphasic pattern of polymerization binding, which may have important
      clinical implications. The apparatus may be useful for gaining better insight
      into a variety of clinically important phenomena related to cyanoacrylate
      polymerization.

PMID- 12006276
TI  - Percutaneous ethanol sclerotherapy of venous malformations of the tongue.
AB  - BACKGROUND AND PURPOSE: Percutaneous ethanol sclerotherapy has been reported to
      be efficacious for head and neck venous malformations. We sought to evaluate the
      safety and efficacy of percutaneous sclerotherapy by using ethanol for treatment
      of symptomatic venous malformations of the tongue. METHODS: Eleven sclerotherapy
      procedures were performed in seven patients from January 1995 to February 2001.
      Patient age ranged from 19 months to 57 years (mean age, 32 years). Four patients
      were male and three were female. Mean follow-up was 36 months. The volume of
      ethanol used per treatment session ranged from 2 to 32 cc (mean, 16 cc). RESULTS:
      Sclerotherapy provided significant improvement or resolution of symptoms for all
      patients. There were no major complications. One patient had a small (3 x 2 cm)
      area of skin blistering at the injection site. All patients experienced pain and
      swelling to a variable degree. Sclerotherapy resulted in resolution of symptoms
      in six of seven patients. Three patients had resolution of symptoms after one
      procedure. Four patients each underwent two sclerotherapy procedures. One patient
      who remained symptomatic but improved after undergoing two procedures underwent
      an anterior glossectomy and is now asymptomatic. CONCLUSION: Percutaneous ethanol
      sclerotherapy is a safe and effective method of treating symptomatic venous
      malformations of the tongue.

PMID- 12006277
TI  - Intraarterial suction thrombectomy in acute stroke.
AB  - Three patients with internal carotid artery thrombus and thrombolysis in
      myocardial infarction (TIMI) 0-1 flow were treated by using intraarterial (IA)
      suction thrombectomy a mean of 4.2 hours after stroke onset. After
      catheterization with a 7F guide-catheter, thrombus was aspirated by using a 60-mL
      syringe. TIMI flow improved to 3 in all patients. The median National Institutes
      of Health Stroke Scale score decreased from 22 (range, 12-23) to 4 (range, 2-22)
      at 3 months. IA suction thrombectomy may be safe and feasible in patients with
      acute stroke.

PMID- 12006278
TI  - Dural arteriovenous fistulae developing at different locations after resolution
      of previous fistulae: report of three cases and review of the literature.
AB  - We present three cases of unusual dural arteriovenous fistulae developing at
      other dural sinuses after resolution of initial lesions by treatment. In all
      three cases, the second lesions developed at different sinuses ipsilateral to the
      initial lesions, and the intervals between the resolution of the initial lesions
      and the appearance of the second lesions was <12 months. Clinical
      characteristics, including those previously reported, are discussed.

PMID- 12006279
TI  - Multiple supra-aortic stenting for Takayasu arteritis: extensive
      revascularization and two-year follow-up.
AB  - A patient with Takayasu arteritis with multiple supra-aortic lesions underwent
      successful treatment with two-staged stent implantation. Stenotic bilateral
      common carotid, innominate, and left subclavian arteries were dilated, and no
      restenosis was observed during the follow-up period of 2 years despite recurrent
      inflammation. Stenting for supra-aortic vessels in cases of Takayasu arteritis
      has rarely been reported, and to our knowledge, this is the first report of
      multiple stent placement for all the supra-aortic branches involved.

PMID- 12006280
TI  - Diffusion tensor MR imaging in diffuse axonal injury.
AB  - BACKGROUND AND PURPOSE: Disruption of the cytoskeletal network and axonal
      membranes characterizes diffuse axonal injury (DAI) in the first few hours after
      traumatic brain injury. Histologic abnormalities seen in DAI hypothetically
      decrease the diffusion along axons and increase the diffusion in directions
      perpendicular to them. DAI therefore is hypothetically associated in the short
      term with decreased diffusion anisotropy. We tested this hypothesis by measuring
      the diffusion characteristics of traumatized brain tissue with use of diffusion
      tensor MR imaging. METHODS: Five patients with mild traumatic brain injuries and
      10 control subjects were studied with CT, conventional MR imaging, and diffusion
      tensor imaging. All patients were examined within 24 hours of injury. In each
      participant, diffusion tensor indices from homologous normal-appearing white
      matter regions of both hemispheres were compared. These indices were also
      compared between homologous regions of each patient and the control group. In two
      patients, diffusion tensor images from the immediate post-trauma period were
      compared with those at 1 month follow-up. RESULTS: Patients displayed significant
      reduction of diffusion anisotropy in several regions compared with the homologous
      ones in the contralateral hemisphere. Such differences were not observed in the
      control subjects. Significant reduction of diffusion anisotropy was also detected
      when diffusion tensor results from the patients were compared with those of the
      controls. This reduction was often less evident 1 month after injury. CONCLUSION:
      White matter regions with reduced anisotropy are detected in the first 24 hours
      after traumatic brain injury. Therefore, diffusion tensor imaging may be a
      powerful technique for in vivo detection of DAI.

PMID- 12006281
TI  - Diffusion anisotropy in the corpus callosum.
AB  - BACKGROUND AND PURPOSE: The corpus callosum is a heterogeneous white-matter tract
      that connects the cerebral hemispheres. The purpose of this investigation was to
      study its microstructural architecture in normal human adult brains by using
      diffusion tensor imaging (DTI). METHODS: Two hundred consecutive patients
      referred for brain MR imaging underwent additional DTI with a high gradient field
      strength applied in six directions. Forty-two patients met the following
      inclusion criteria: 1) normal brain and 2) age greater than 18 years. Anisotropy
      maps were generated, and regions of interest were drawn around specified regions
      within the corpus callosum. Results were stratified by sex and age. In addition,
      available histologic specimens of the corpus callosum from cadaver brains were
      analyzed with conventional and specialized vascular staining. RESULTS: Anisotropy
      values in the various regions of the corpus callosum differed significantly.
      Average values of the anisotropy index for the genu, body, and splenium of the
      corpus callosum were 0.400, 0.456, and 0.539, respectively. The differences
      between these values are statistically significant (P <.01). Increased anisotropy
      was present in posterior areas in both sexes and in all three age groups
      examined. CONCLUSION: The results of this investigation show a statistically
      significant increase in anisotropy of the corpus callosum in its more posterior
      portions compared with its more anterior portions across sex and age groups.
      Although the microstructural etiology for this apparent increase in anisotropy is
      unclear, a number of possible mechanisms are presented.

PMID- 12006282
TI  - Apparent diffusion coefficient value of the hippocampus in patients with
      hippocampal sclerosis and in healthy volunteers.
AB  - BACKGROUND AND PURPOSE: MR diffusion-weighted (DW) imaging with apparent
      diffusion coefficient (ADC) has had widespread use clinically in a variety of
      intracranial diseases; however, only a few studies report ADC changes in patients
      with hippocampal sclerosis. We sought to determine the ability of ADC to
      lateralize the epileptogenic lesion in patients with hippocampal sclerosis.
      METHODS: Nineteen healthy volunteers and 18 patients with intractable temporal
      lobe epilepsy whose MR imaging diagnosis was unilateral hippocampal sclerosis
      were examined prospectively with DW imaging and ADC mapping. DW images were
      obtained at 1.5 T with a spin-echo echo-planar sequence (6500/103 [TR/TE]) with
      variable diffusion gradients. ADCs were calculated from bilateral hippocampi. The
      ability of DW imaging and ADC to lateralize the lesion was evaluated visually and
      by comparing ADC values between healthy volunteers and patients with hippocampal
      sclerosis. RESULTS: In all patients, visual assessment of DW images failed to
      lateralize the lesion. However, the mean ADC value measured at the hippocampal
      area was significantly higher on the lesion side than on the contralateral side
      (P <.001). The overall correct lateralization rate of ADC was 100% (18 of 18
      patients). Mean ADC in sclerotic hippocampi was also significantly higher than
      that in healthy volunteers. The normal-appearing hippocampus of the contralateral
      side in the patients had higher ADC values compared with those of healthy
      volunteers (P =.045). CONCLUSION: ADC can be used as a complementary tool in
      lateralizing the epileptogenic lesion in patients with hippocampal sclerosis,
      although the practical role of ADC value is yet to be determined in patients with
      inconclusive MR imaging findings.

PMID- 12006283
TI  - Mitochondrial encephalomyopathy: comparison of conventional MR imaging with
      diffusion-weighted and diffusion tensor imaging: case report.
AB  - SUMMARY: Conventional MR imaging, MR spectroscopy, diffusion-weighted imaging,
      and diffusion tensor imaging were performed in a 5-month-old male patient with
      mitochondrial encephalomyopathy. On conventional T2-weighted MR images,
      symmetric, confluent high signal intensity was found in the temporoparietal white
      matter. A large lactate peak and decreased N-acetylaspartate were found in this
      region on proton MR spectroscopic images. Diffusion-weighted imaging showed
      increased apparent diffusion coefficient, representing vasogenic edema. Diffusion
      tensor imaging revealed decreased anisotropy, consistent with injury to the
      oligodendro-axonal unit. A muscle biopsy specimen revealed an isolated complex
      III enzyme respiratory chain deficiency. Diffusion-weighted and diffusion tensor
      imaging are valuable techniques for the characterization of hyperintense lesions
      on T2-weighted MR images in cases of mitochondrial encephalomyopathy.

PMID- 12006284
TI  - MR imaging of leptomeningeal metastases: comparison of three sequences.
AB  - BACKGROUND AND PURPOSE: Recent work has shown that fluid-attenuated inversion
      recovery (FLAIR) imaging with contrast enhancement is highly sensitive for
      detecting subarachnoid space disease. We hypothesized that contrast-enhanced
      FLAIR imaging has superior sensitivity to contrast-enhanced T1-weighted MR
      imaging in detecting leptomeningeal metastases. METHODS: Sixty-eight patients
      referred for suspected leptomeningeal metastases underwent 74 MR imaging studies.
      The patients had either temporally related cytologic proof of leptomeningeal
      metastases or negative results of clinical follow-up confirming absence of
      leptomeningeal metastases. The MR imaging examinations included unenhanced and
      contrast-enhanced FLAIR images and contrast-enhanced T1-weighted MR images that
      were independently reviewed by two neuroradiologists blinded to the results of
      cytology. Each of the three sequences was reviewed individually and separately
      and was assigned a score of positive or negative for leptomeningeal metastases.
      Discrepancies were settled by consensus. RESULTS: Of the 17 studies of patients
      with cytology-proven leptomeningeal metastases, two were positive based on
      unenhanced FLAIR images, seven were positive based on contrast-enhanced FLAIR
      images, and 10 were positive based on contrast-enhanced T1-weighted MR images. Of
      the 57 studies of patients without leptomeningeal metastases, 53 were negative
      based on unenhanced FLAIR images, 50 were negative based on contrast-enhanced
      FLAIR images, and 53 were negative based on contrast-enhanced T1-weighted MR
      images. The sensitivity and specificity of unenhanced FLAIR images for detecting
      leptomeningeal metastases were 12% (two of 17) and 93% (53 of 57), respectively.
      The sensitivity and specificity for contrast-enhanced FLAIR images for detecting
      leptomeningeal metastases were 41% (seven of 17) and 88% (50 of 57),
      respectively. The sensitivity and specificity of contrast-enhanced T1-weighted MR
      images for detecting leptomeningeal metastases were 59% (10 of 17) and 93% (53 of
      57), respectively. CONCLUSION: Contrast-enhanced fast FLAIR sequences are less
      sensitive than standard contrast-enhanced T1-weighted MR sequences in detecting
      intracranial neoplastic leptomeningeal disease.

PMID- 12006285
TI  - Correlation of high signal intensity of the pituitary stalk in macroadenoma and
      postoperative diabetes insipidus.
AB  - BACKGROUND AND PURPOSE: High signal intensity (HSI) at the pituitary stalk is
      reported in pituitary adenomas. Our purpose was to clarify how and when this HSI
      formed, its long-term fate, and its relation to the function of
      infundibuloneurohypophyseal (INH) system. METHODS: Twenty-two patients with
      pituitary adenoma and supradiaphragmatic extension underwent 1.5-T MR imaging.
      Patients were assigned to two groups A (n = 18; those with stalk tip HSI) and B
      (n = 4; those without HSI) on postoperative T1-weighted images. Endocrine status
      was postoperatively evaluated and compared in both groups. RESULTS: Group A
      patients did not have postoperative permanent diabetes insipidus (DI).
      Preoperative images in 17 patients revealed linear or ovoid HSI on the adenoma
      surface immediately above the diaphragma sellae. Of these, two with a poorly
      developed diaphragma sellae had HSI near the median eminence and inside the sella
      turcica. HSI was not apparent in the remaining patient with a giant, irregularly
      shaped adenoma. In group B, three patients had permanent DI. No patient had HSI
      on preoperative images. CONCLUSION: Postoperative pituitary stalk HSI is derived
      from preoperative supradiaphragmatic HSI on the adenoma surface. The suspected
      mechanism is blockage of the hypophyseal-pituitary axis, with an accumulation of
      neurosecretory granules at the diaphragmatic level. Diaphragmatic shape may
      influence the location of HSI. The shape and location of HSI are essentially
      stable for years after surgery. No patients with permanent DI had HSI before or
      after surgery. HIS at the pituitary stalk tip is a useful landmark for predicting
      functional integrity of the INH system in patients with a large pituitary
      adenoma.

PMID- 12006286
TI  - Dynamic, contrast-enhanced CT of human brain tumors: quantitative assessment of
      blood volume, blood flow, and microvascular permeability: report of two cases.
AB  - We present two patients with metastatic brain tumors who underwent dynamic
      contrast-enhanced CT that yielded estimates of blood volume, blood flow, and
      microvascular permeability. For one patient, these CT-based quantifications were
      compared with contrast-enhanced MR-based assessments of fractional blood volume
      and permeability. Regional blood volume heterogeneity patterns were consistent
      between both CT- and MR imaging-based mapping. Permeability variations across the
      tumor, however, were less consistent, perhaps because of differences between
      ionic and non-ionic contrast agents. The advantages of dynamic contrast-enhanced
      CT in comparison with dynamic, contrast-enhanced MR imaging for microvascular
      quantifications are its availability and lower costs, applicability in the
      presence of MR imaging contraindications, and potentially more accurate analyses.
      The disadvantages are its limited anatomic coverage, radiation exposure, and the
      need for injection of a contrast agent.

PMID- 12006287
TI  - Diffuse metabolic abnormalities in reversible posterior leukoencephalopathy
      syndrome.
AB  - Two cases of reversible posterior leukoencephalopathy syndrome were examined with
      proton MR spectroscopic imaging. Widespread metabolic abnormalities, consisting
      of increased choline and creatine levels and mildly decreased N-acetylaspartate,
      occurred in regions with both normal and abnormal MR imaging appearances. In one
      case for which proton MR spectroscopic imaging follow-up was available, all
      metabolite levels had returned to normal by 2 months. Proton MR spectroscopic
      imaging may be helpful for the diagnosis and investigation of the underlying
      pathophysiology of reversible posterior leukoencephalopathy syndrome.

PMID- 12006288
TI  - Mucosa-associated lymphoid tissue lymphoma of the pituitary gland: MR imaging
      features.
AB  - We report the MR features in a previously healthy patient with mucosa-associated
      lymphoid tissue lymphoma of the pituitary gland. The MR images showed a
      homogeneously enhancing solid mass in the sellar region and both parasellar
      regions; this mass extended through the bilateral foramina ovale along the third
      branches of the trigeminal nerves. The mass completely encircled the cavernous
      segments of both internal carotid arteries without narrowing the lumen.
      Gadopentetate dimeglumine-enhanced T1-weighted MR images showed homogeneous,
      strong enhancement of the mass.

PMID- 12006289
TI  - Unusual small choroid plexus cyst obstructing the foramen of monroe: case report.
AB  - This is a case report of unusual case of choroid plexus cyst at the right foramen
      of Monro in the anterior third ventricle that caused unilateral obstructive
      hydrocephalus. The value of small-FOV thin-section MR imaging in the diagnosis of
      small lesions of the foramen of Monroe is demonstrated. The immunohistochemical
      findings in choroid epithelial cysts in comparison with those of other types of
      cysts at this location are discussed.

PMID- 12006290
TI  - Cortical dysplasia localized by [11C]methionine positron emission tomography:
      case report.
AB  - Numerous functional neuroimaging techniques have progressively been added to the
      presurgical evaluation of refractory partial epilepsies. These investigations can
      help confirm the origin of seizure onset previously suggested by MR imaging and
      electro-clinical data, provide independent prognostic information, and provide
      critical diagnostic value when MR imaging results are strictly normal or show
      multifocal abnormalities. Of the various functional neuroimaging modalities,
      [11C]methionine positron emission tomography for methionine uptake into seizure
      foci is still in the preliminary stages of investigation. A single case of
      medically intractable epilepsy with focal cortical dysplasia documented by
      [11C]methionine positron emission tomography and possible hypotheses to explain
      the methionine uptake into the seizure focus are described below.

PMID- 12006291
TI  - Diffusion-weighted imaging for differentiating recurrent cholesteatoma from
      granulation tissue after mastoidectomy: case report.
AB  - Identification of recurrent cholesteatoma and differentiation from postoperative
      granulation tissue is important in a patient who has undergone mastoidectomy for
      cholesteatoma. We describe the diffusion-weighted imaging findings and apparent
      diffusion coefficient values in a case of recurrent cholesteatoma. This case
      suggests possible differentiation of cholesteatoma from granulation tissue on the
      basis of diffusion-weighted imaging findings.

PMID- 12006292
TI  - Granular cell tumor of the palate: a case report.
AB  - Granular cell tumor (GCT) is an infrequent benign neoplasm, which Abrikosoff
      accurately described in 1926. GCT probably has a neural crest cell origin. We
      present the clinical and imaging findings in a 45-year-old woman with a GCT
      involving the palate. CT and MR imaging revealed perineural tumor spread along
      the greater and lesser palatine nerves. We emphasize the peculiarity of the
      palatine location and the perineural spread of GCTs.

PMID- 12006293
TI  - Posttransplantation lymphoproliferative disorder of the paranasal sinuses
      mimicking invasive fungal sinusitis: case report.
AB  - Posttransplantation lymphoproliferative disorder (PTLD) is a challenging
      complication associated with organ transplantation and is usually fatal if
      untreated. We describe the case of a transplant recipient who presented with
      rapidly progressive cranial nerve palsies due to PTLD that originated in the
      sphenoid sinus. In this case, the clinical and radiologic presentation of PTLD
      mimicked invasive fungal disease. Because the management of PTLD and the
      management of invasive fungal infection are vastly different, prompt pathologic
      diagnosis is required.

PMID- 12006294
TI  - Detection of spinal dural arteriovenous fistulae with MR imaging and contrast
      enhanced MR angiography: sensitivity, specificity, and prediction of vertebral
      level.
AB  - BACKGROUND AND PURPOSE: MR imaging and contrast-enhanced MR angiography have been
      used to detect evidence of spinal dural arteriovenous fistulae (AVF); however,
      the sensitivity and specificity of these techniques have not been shown. The
      purpose of this study was to establish the sensitivity, specificity, and accuracy
      of MR imaging alone compared with MR imaging plus MR angiography in determining
      whether dural AVF are present and to establish the accuracy of MR angiography in
      predicting fistula level. METHODS: Twenty patients with surgically proven dural
      AVF (diagnosed with radiographic digital subtraction angiography) and 11 control
      patients who had normal digital subtraction angiography findings underwent
      routine MR imaging plus 3D contrast-enhanced MR angiography of the spine. Images
      were reviewed in two stages (stage I, MR images only; stage II, MR images plus MR
      angiograms) by three neuroradiologists who were blinded to the final diagnoses.
      RESULTS: The sensitivity, specificity, and accuracy of the three reviewers in
      detecting the presence of fistulae ranged from 85% to 90%, from 82% to 100%, and
      from 87% to 90%, respectively, for stage I, compared with values of 80% to 100%,
      82%, and 81% to 94%, respectively, for stage II. For each reviewer, there was no
      significant difference between the values for stages I and II; however, among the
      reviewers, one of the more experienced neuroradiologists had significantly
      greater sensitivity than a less experienced neuroradiologist for stage II. On
      average, the percentage of true positive results for which the correct fistula
      level was predicted increased from 15% for stage I to 50% for stage II, and the
      correct level +/- one level was predicted in 73% for stage II. MR evidence of
      increased intradural vascularity was significantly greater in patients with dural
      AVF. CONCLUSION: The addition of MR angiography to standard MR imaging of the
      spine may improve sensitivity in the detection of spinal dural fistulae. The
      principal benefit of MR angiography is in the improved localization of the
      vertebral level of the fistula, which potentially expedites the subsequent
      digital subtraction angiography study.

PMID- 12006295
TI  - Paradoxical cerebral arterial embolization of cement during intraoperative
      vertebroplasty: case report.
AB  - Paradoxical cerebral embolism of cement occurred in a 78-year-old woman after
      cement-assisted transpedicular spinal fixation surgery. Multiple pulmonary emboli
      of polymethylmethacrylate precipitated pulmonary hypertension and right-to-left
      shunting into the systemic circulation through a patent foramen ovale. This rare
      complication occurred because of failure to recognize venous migration of cement
      during the procedure and the injection of multiple levels in one setting.
      Although this was an open procedure, the technical aspects were the same as for
      vertebroplasty and the precautions should be applied to percutaneous
      vertebroplasty.

PMID- 12006296
TI  - MR imaging assessment of myelination in the very preterm brain.
AB  - BACKGROUND AND PURPOSE: MR imaging was performed in very preterm infants by using
      an MR imager in the neonatal intensive care unit. The aims of this study were to
      assess the development of myelination in the preterm brain based on MR imaging
      findings and to compare the ability of T1-weighted conventional spin-echo,
      inversion recovery fast spin-echo, and T2-weighted fast spin-echo MR imaging to
      show myelination in these infants. METHODS: MR imaging was performed for 26
      preterm infants with a median gestational age of 28 weeks who had normal
      neurodevelopmental outcomes at 2 years corrected age. RESULTS: Myelin was evident
      in the gracile and cuneate nuclei and fasciculi, vestibular nuclei, cerebellar
      vermis, inferior and superior cerebellar peduncles, dentate nucleus, medial
      longitudinal fasciculus, medial geniculate bodies, subthalamic nuclei, inferior
      olivary nuclei, ventrolateral nuclei of the thalamus, decussation of the superior
      cerebellar peduncles, medial lemnisci, lateral lemnisci, and inferior colliculi
      at < or = 28 weeks gestational age. From this gestational age, myelination was
      not visualized at any new site until 36 weeks gestational age, when myelin was
      visualized in the corona radiata, posterior limb of the internal capsule,
      corticospinal tracts of the precentral and postcentral gyri, and lateral
      geniculate bodies. T2-weighted fast spin-echo MR imaging showed myelin in gray
      matter nuclei at an earlier gestational age than did T1-weighted conventional
      spin-echo or inversion recovery fast spin-echo MR imaging. T1-weighted
      conventional spin-echo MR imaging showed myelin earlier in some white matter
      tracts in the preterm brain. CONCLUSION: Myelination was evident in numerous gray
      and white matter structures in the very preterm brain. A knowledge of myelination
      milestones will allow delays to be detected at an early stage.

PMID- 12006297
TI  - Developmental delay in children: assessment with proton MR spectroscopy.
AB  - BACKGROUND AND PURPOSE: The cause of developmental delay frequently is unknown,
      and clinicians and families can be frustrated by the lack of neuroimaging
      correlation especially when considering therapeutic options and long-term
      prognosis. We sought to determine if proton MR spectroscopy can depict
      abnormalities in patients with developmental delay who have structurally normal
      brain MR images. METHODS: Children with developmental delay who were older than 2
      years (mean age, 5.0 years; range, 3.0-10.0 years) and those aged 2 years or
      younger (mean age, 1.5 years; range, 0.5-2.0 years) and age-matched control
      subjects for each patient group underwent brain MR imaging and proton MR
      spectroscopy. A point-resolved spectroscopy sequence (2000/144 [TR/TE]) was used.
      Voxels (8 cm(3)) were placed in the subcortical white matter of the frontal and
      parieto-occipital lobes bilaterally. N-acetylaspartate (NAA)/creatine (Cr) and
      choline (Cho)/Cr ratios were assessed. RESULTS: All patients had normal brain MR
      images. In children with developmental delay who were aged 2 years or younger, no
      statistically significant differences were detected in the NAA/Cr or Cho/Cr
      ratios compared with those of the control subjects. In children with
      developmental delay who were older than 2 years, decreases in the NAA/Cr ratio
      were observed in frontal (P <.001) and parieto-occipital (P <.017) subcortical
      white matter, and elevations in the Cho/Cr ratio were detected in the frontal (P
      <.24) and parieto-occipital (P <.002) subcortical white matter compared with age
      matched control subjects. CONCLUSIONS: In children with developmental delay who
      are older than 2 years, proton MR spectroscopy depicted abnormalities in the
      NAA/Cr and Cho/Cr ratios. Proton MR spectroscopy should be performed as part of
      the neuroimaging evaluation of developmental delay. Further studies will be
      needed to determine if abnormalities detected with proton MR spectroscopy can be
      used as a diagnostic tool and neuroimaging marker to assess long-term functional
      outcome.

PMID- 12006298
TI  - Risk of cerebral angiographic complications, injection volumes, and rates.

PMID- 12006299
TI  - White-matter hyperintensities and subcortical infarcts as predictors of shunt
      surgery outcome.

PMID- 12006300
TI  - Reality orientation: a welcome return?

PMID- 12006301
TI  - The integrated care pathway epidemic--is stroke next?

PMID- 12006302
TI  - Mortality from pulmonary embolism after acute stroke: can we do better?

PMID- 12006303
TI  - Low level social engagement as a precursor of mortality among people in later
      life.
AB  - OBJECTIVE: to examine if a low level of social engagement is a precursor for
      mortality. METHODS: a case-control design, controlling for physical health, age
      and sex examining social engagement and morale. We took measures on 3 occasions,
      4 years apart. RESULTS: a low level of social engagement was an important
      precursor of 8-year mortality. There were intermediate significant differences
      for social engagement, physical health and morale. CONCLUSIONS: levels of social
      engagement either have a direct effect on mortality, or represent hidden health
      problems, acting as a marker for later ill health. Social engagement may also
      have a role in intermediate declines in physical health and morale.

PMID- 12006304
TI  - Agreement between measured and self-reported weight in older women. Results from
      the British Women's Heart and Health Study.
AB  - BACKGROUND: previous studies of the accuracy of self-reported weight have been
      criticised for using inadequate methods and have included only young or middle
      aged adults. Self-report is more likely to be relied upon in both clinical and
      research practice in older age groups. The cultural pressures that may cause the
      tendency among younger women to underestimate their weight, particularly when
      they are overweight, may operate differently in older women. OBJECTIVE: to
      determine the accuracy of self-reported weight among older women. METHODS:
      national cross sectional survey of women aged 60-79 from 9 towns across England,
      Scotland and Wales. Self-reported weight from a participant questionnaire was
      compared to measured weight at examination. RESULTS: of 2729 women who were
      invited, 1636 (60%) returned the questionnaire (of whom 1549 gave a self-reported
      weight) and 1384 (51%) attended for examination (of whom 1381 were weighed). In
      total there were 1310 (48% of the total invited sample) with complete self-report
      and measured weight. Self-reported and measured weight were highly correlated
      (Pearson's correlation coefficient, 0.982 95% confidence interval, 0.979-0.983)
      and self-reported weight differed from measured weight by only 1.0 kg (95%
      confidence interval 0.8 kg, 1.1 kg) on average. However, a difference plot, with
      limits of agreement at -4.0 kg to +6.0 kg (95% confidence intervals: lower limit 
      4.3 kg, -3.8 kg; upper limit +5.7 kg, +6.2 kg) revealed poor agreement between
      methods. Obese individuals, in particular, were more likely to underestimate
      their weight. CONCLUSIONS: though self-report of weight by women in their 60s and
      70s is highly correlated, at an individual level differences between self-report
      and measured weight are frequently large. Obese individuals, in particular, tend
      to underestimate their weight. Self-report of weight should not be relied upon in
      prospective epidemiological studies or clinical practice when accuracy at the
      level of the individual is required.

PMID- 12006305
TI  - Does an integrated care pathway improve processes of care in stroke
      rehabilitation? A randomized controlled trial.
AB  - OBJECTIVE: to evaluate whether integrated care pathways improve the processes of
      care in stroke rehabilitation. DESIGN: comparison of processes of care data
      collected in a randomized controlled trial. PARTICIPANTS: acute stroke patients
      undergoing rehabilitation randomized to receive integrated care pathways
      management (n=76) or conventional multidisciplinary care (n=76). MEASUREMENTS:
      proportion of patients meeting recommended standards for processes of care using
      a validated stroke audit tool. RESULTS: integrated care pathways methodology was
      associated with higher frequency of stroke specific assessments, notably testing
      for inattention (84% versus 60%; P=0.015) and nutritional assessment (74% versus
      22%, P<0.001). Documentation of provision of certain information to
      patients/carers (89% versus 70%; P=0.024) and early discharge notification to
      general practitioners (80% versus 45%; P<0.001) were also more common in this
      group. There were no significant differences in the processes of
      interdisciplinary co-ordination and patient management between the integrated
      care pathways group and the control group. CONCLUSION: integrated care pathways
      may improve assessment and communication, even in specialist stroke settings.

PMID- 12006306
TI  - Blood pressure changes on upright tilting predict falls in older people.
AB  - BACKGROUND: orthostatic hypotension may be an important risk factor for falls,
      though this has not yet been demonstrated in prospective studies. This may be
      because conventional methods of measuring blood pressure changes are too
      imprecise and not optimally timed. OBJECTIVES: to determine whether changes in
      blood pressure induced by upright tilt are associated with falls in older people,
      and whether medication use and symptoms of dizziness are associated with blood
      pressure changes and falls. METHODS: seventy men and women aged 62-92 years
      participated. We measured blood pressure with a plethysmograph monitor
      continuously before and after upright tilt. We recorded medication use and
      symptoms of dizziness in response to the tilt. Subjects were then followed up for
      12 months to determine the incidence of falls. RESULTS: subjects who fell in the
      follow-up period had significantly greater decreases in systolic blood pressure
      when tilted than those who did not fall. Furthermore, those who had unstable
      systolic blood pressure during the 3 minutes after tilting, in addition to large
      blood pressure drops, had a two-fold increased risk of falling compared with
      those with neither of these conditions. Symptoms of dizziness on tilting were
      uncommon and not associated with blood pressure or heart rate changes, medication
      use, or falls incidence. Antidepressant and antihypertensive medication use were
      associated with decreases in diastolic rather than systolic blood pressure, but
      were not associated with falls. CONCLUSIONS: these findings indicate that both
      the decrease in blood pressure and the unstable nature of the blood pressure
      response following upright tilt are useful predictors of falls in older people.

PMID- 12006307
TI  - Are older people willing to give up their place in the queue for cardiac surgery
      to a younger person?
AB  - OBJECTIVES: to measure whether people aged 65 and over living in Britain would be
      willing to give up their place on the cardiac surgery waiting list for someone
      younger than them. METHODS: two British surveys, based on random types of people
      sampled for the Office for National Statistics Omnibus Surveys, identified
      respondents aged 65 and over for a module on waiting lists. They were asked to
      imagine they had a heart condition that required surgery, and that they were on
      an NHS waiting list. They were then asked if they would be prepared to give up
      their place on the cardiac surgery waiting list to a younger person (aged 45).
      The study compared responses to one of two relative waiting list time frames (6
      and 12 months). SETTING: two national random samples of the British public aged
      65 and over. RESULTS: fifty eight per cent and 62% of Omnibus respondents aged 65
      and over responded that it was not right to give up their place on the cardiac
      surgery waiting list for someone younger in relation to a 6 and 12 month wait
      respectively. Thirty seven per cent and 34% of each group of Omnibus respondents
      aged 65+ said it was right to give up their place on the cardiac surgery waiting
      list for someone younger than them, in relation to a 6 and 12 month relative
      waiting period respectively. Thus the length of the wait had little effect on
      response among British respondents. The proportions who were willing to cede
      priority are far less than that reported in a comparable Italian survey.
      Consistent with the Italian survey, willingness to cede priority increased with
      age. CONCLUSIONS: most older people in Britain do not wish to cede priority on
      the waiting list for cardiac surgery to people younger than themselves, although
      willingness to give up one's place increased with age. The specific time frame
      did not have an impact on people's responses. The increase in willingness to cede
      priority with older age could be interpreted as older people valuing themselves
      less, or that they feel that they have had their 'fair innings' and are willing
      to give younger people the chance of reaching their age. It could even reflect a
      cohort effect. It is likely that ageing 'baby boomers' may be even less willing
      to give up their place in the health service queue and will be more assertive
      about their right to equity in health care provision.

PMID- 12006308
TI  - Predictors of cognitive improvement after reality orientation in Alzheimer's
      disease.
AB  - BACKGROUND: there is increasing evidence to support the efficacy of reality
      orientation in cognitive deficits in patients with Alzheimer's disease. The
      clinical characteristics of patients who respond to reality orientation are
      poorly understood; this knowledge could be important, given that the provision of
      reality orientation therapy is labour-intensive and may provoke emotional
      distress. AIM: to evaluate retrospectively which demographic and clinical
      characteristics of Alzheimer's patients predict cognitive outcomes. METHOD: we
      analysed 38 mild-to-moderately demented outpatients who regularly attended a one
      month formal reality orientation programme. The mini mental state examination
      score changes from baseline-and immediately after-reality orientation were
      correlated with demographic and pre-treatment clinical characteristics by a
      linear regression analysis. RESULTS: short-term responsiveness to reality
      orientation was significantly predicted by a lower level of cognitive functioning
      (as measured by the mini mental state examination) at baseline and by the absence
      of euphoria, accounting together for 57.6% of variance. CONCLUSION: a lower mini
      mental state examination and the absence of euphoric behaviour in patients with
      mild-to-moderate Alzheimer's disease may predict a good cognitive outcome of
      reality orientation therapy.

PMID- 12006309
TI  - Standard indicators of deprivation: do they disadvantage older people?
AB  - BACKGROUND: ecological studies using standard generic indicators of material
      deprivation have suggested that there is little social inequality at older ages.
      This may be because the indicators used were designed for studying younger
      populations and may be biased against older people. OBJECTIVE: to examine the
      association, at different ages, between mortality ratios, indicators of
      deprivation and an indicator of poverty, which can be easily tailored to
      different age groups. METHODS: an ecological study comparing mortality ratios and
      indicators of deprivation and poverty. We calculated standardised mortality
      ratios for those under and over 75 years, using all deaths for Northern Ireland
      between 1990 and 1998. We calculated levels of income support uptake (a social
      security benefit) for similar age groups. We derived three commonly used
      indicators of deprivation (Townsend, Carstairs and Jarman) from census data. We
      assessed the strength of association between the mortality ratios and the
      indicators of poverty and deprivation using Pearson correlation coefficients.
      RESULTS: 11.1% of people under 75 and 24.3% of those over 75 were on income
      support. Income support uptake for those over 75 was strongly correlated with
      deprivation indicators. There was a much weaker relationship between disadvantage
      and mortality at older ages, especially in women. Poverty, as measured by income
      support ratios, was more highly correlated with mortality than any other
      deprivation indicator-especially at older ages and in women, where income support
      uptake produced the highest correlations. CONCLUSIONS: many of the commonly used
      indicators of deprivation are poorly suited to studying inequalities in health in
      older people. Uptake of income support offers many advantages over conventional
      indicators.

PMID- 12006310
TI  - Evaluation of a nurse-led falls prevention programme versus usual care: a
      randomized controlled trial.
AB  - OBJECTIVE: to evaluate a nurse-led management plan and care pathway for older
      people discharged from an Accident and Emergency Department after a fall. DESIGN:
      randomized controlled trial. SETTING: a large teaching hospital. SUBJECTS: 348
      consecutive patients aged 65 or over attending the Accident and Emergency
      Department with a fall. INTERVENTIONS: we randomized patients to falls nurse
      intervention or usual care. Within 4 weeks, the intervention group received a
      home assessment to address easily modifiable risk factors for falls. This
      included assessments of medication, ECG, blood pressure, cognition, visual
      acuity, hearing, vestibular dysfunction, balance, mobility, feet and footwear.
      All patients were given advice and education about general safety in the home.
      MAIN OUTCOME MEASURES: Further falls, functional ability, re-attendance at the
      Accident and Emergency Department and admission to hospital. RESULTS: at 6 months
      post-Index fall, 36 patients in the intervention group and 39 patients in the
      control group had had 89 and 145 falls respectively. Although the intervention
      group had less falls, this was not significant (P>0.05). Similarly, the
      intervention group had fewer fall-related admissions and bed days (8 and 69
      respectively) than the control group (10 and 233 respectively). The intervention
      group scored significantly higher in indicators of function (P<0.05) and mobility
      within the community (P<0.02). CONCLUSIONS: although the differences were not
      significant, patients in the intervention group had fewer falls, less hospital
      attendances and spent less time in hospital. Moreover, patients in the
      intervention group were more functionally independent at 6 months post-Index
      fall.

PMID- 12006311
TI  - Evaluation of skills and knowledge on orthostatic blood pressure measurements in
      elderly patients.
AB  - OBJECTIVES: orthostatic hypotension is a common and potentially dangerous
      condition in elderly patients, often accompanied by dizziness and falls. To
      diagnose orthostatic hypotension, many physicians rely on blood pressure
      measurements performed by nurses. DESIGN: observational and descriptive study.
      SETTING: departments of Internal Medicine, Geriatric Medicine, and Surgery in
      eight hospitals throughout the Netherlands. SUBJECTS: 170 nurses working with
      elderly people in a general hospital. We selected a sample of 10 nurses on 17
      participating wards. METHODS: to evaluate nurses' skills and knowledge on blood
      pressure measurements to diagnose orthostatic hypotension, we performed
      standardized observations, based on published guidelines, of supine and standing
      blood pressure determination in patients over 65 years. RESULTS: the most
      important deviations in technique of orthostatic blood pressure measurement from
      the published guidelines were: time between measuring supine and standing blood
      pressure varied from 0-30 minutes; in 28% the arm position was not at heart level
      during standing blood pressure measurements; in 46% the cuff was placed
      incorrectly. CONCLUSIONS: the skills and knowledge of nurses to measure supine
      and standing blood pressure are inaccurate for diagnosing orthostatic hypotension
      in elderly patients. Large differences in measurement technique and timing of
      standing blood pressure could influence the individual detection and treatment of
      orthostatic hypotension and the reported prevalence of orthostatic hypotension.
      The blood pressure measurement procedure to diagnose orthostatic hypotension
      needs more standardization and implementation of guidelines in daily practice.

PMID- 12006312
TI  - Calcium channel blocker use and gastrointestinal tract bleeding among older
      adults.

PMID- 12006313
TI  - Chronic pain, bereavement and overdose in a depressed elderly woman.

PMID- 12006314
TI  - Endocarditis in older people.

PMID- 12006315
TI  - Follow up studies in rheumatoid arthritis.

PMID- 12006316
TI  - Sjogren's syndrome criteria.

PMID- 12006317
TI  - Multicentric reticulohistiocytosis: a rare cause of erosive arthropathy of the
      distal interphalangeal finger joints.
AB  - BACKGROUND: Multicentric reticulohistiocytosis (MRH) is a rare systemic disease,
      presenting with typical skin abnormalities and erosive polyarthritis, which is
      often associated with malignancy. CASE REPORT: A case of MRH arthropathy, in
      which the typical nodular skin manifestation of the disease was absent, is
      described in a patient with a past history of breast cancer and no evidence of
      recurrent or new malignancy. RESULTS: Careful clinical and roentgenological
      evaluation disclosed important clues to differentiate this condition from other
      more common distal interphalangeal arthritides--namely, osteoarthritis and its
      "erosive" variant, rheumatoid arthritis, psoriatic arthritis, tophaceous gout,
      dialysis related hand arthropathy, and from the rarer fibroblastic rheumatism,
      all of which can be mimicked by MRH. Histopathology showed the characteristic
      histiocytic and multinucleated giant cell infiltrate with ground glass cytoplasm,
      and immunohistochemical analysis showed markers evocative of a
      monocyte/macrophage origin of MRH.

PMID- 12006318
TI  - Identification of the advanced glycation end products N(epsilon)
      carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis.
AB  - BACKGROUND: Generation of advanced glycation end products (AGEs) is an inevitable
      process in vivo and can be accelerated under pathological conditions such as
      oxidative stress. In serum and synovial fluid of patients with rheumatoid
      arthritis (RA) raised AGE levels have been found. OBJECTIVE: To determine the
      presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in
      RA synovial tissue by immunohistology. METHODS: Frozen synovial tissue samples
      from 10 patients with RA and eight controls (four patients without joint disease
      and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG
      and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline
      phosphatase (chromogen fuchsin). Cell differentiation was performed with
      antibodies against CD68, CD45RO, and CD20. RESULTS: CML was detected in the
      synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial
      specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive
      immunostaining for CML, whereas B cells were negative. Staining in OA synovial
      sublining was weak compared with RA. CONCLUSIONS: CML was detected for the first
      time in RA and OA synovial tissue. Different patterns of immunostaining in RA and
      OA and the presence of CML on macrophages and T cells, suggest a role for CML in
      the pathogenesis of RA. This might be due to presentation of new epitopes which
      can maintain or even trigger an autoimmune response.

PMID- 12006319
TI  - Colchicum autumnale from Het Cruydtboeck by Rembertus Dodonaeus.

PMID- 12006320
TI  - The value of synovial fluid assays in the diagnosis of joint disease: a
      literature survey.
AB  - OBJECTIVE: To carry out a critical appraisal of the literature in an attempt to
      assess the current value of synovial fluid (SF) analysis in the diagnosis of
      joint disease. METHODS: A literature search was undertaken using the Medline,
      Biomed, Bids, Pubmed, and Embase electronic databases using the keywords:
      synovial fluid (SF) analysis, SF crystals, joint sepsis, acute arthritis, and SF
      cell counts, cytology, biomarkers, and microbiology. RESULTS: Publications fell
      into three main categories. Firstly, reports assessing the value of the three
      traditional assays (microbiology, white blood cell counts, and microscopy for
      pathogenic crystals). For these quality control evidence was found to be sparse,
      and tests for sensitivity, specificity, and reliability showed worrying
      variations. These poor standards in SF analysis may be due to lack of inclusion
      of some tests within routine pathology services. Secondly, claims for the
      usefulness of "new" assays (cytology and biochemical markers). For cytology, the
      supporting evidence was mainly anecdotal and there were no reports on
      specificity, sensitivity, and reliability. Interpretation difficulties are a
      major hindrance to the clinical use of biochemical assays, which remain primarily
      research tools. Finally, work on the diagnostic value of SF analysis in general.
      The appraisal confirmed that SF analysis remains of major diagnostic value in
      acute arthritis, where septic arthritis or crystal arthropathy is suspected, and
      in intercritical gout. CONCLUSIONS: Given the importance of SF tests,
      rationalisation of their use, together with improved quality control, should be
      immediate priorities. Further investigation is recommended into the contribution
      of SF inspection and white cell counts to diagnosis, as well as of the
      specificity and sensitivity of SF microbiological assays, crystal identification,
      and cytology.

PMID- 12006321
TI  - Sarcoid arthritis: clinical characteristics, diagnostic aspects, and risk
      factors.
AB  - OBJECTIVES: (a) To describe the clinical characteristics of acute sarcoid
      arthritis and the diagnostic value of its presenting clinical features; (b) to
      evaluate whether disease onset is seasonal; and (c) to evaluate whether smoking
      behaviour or the presence of HLA class II alleles is a risk factor for the
      disease. METHODS: 579 consecutive patients with recent onset arthritis who had
      been newly referred to a rheumatology outpatient clinic were included in a
      prospective cohort study. The presenting clinical features, the smoking
      behaviour, and the results of HLA-DQ and HLA-DR DNA typing of 55 patients with
      sarcoid arthritis, 524 patients with other arthritides of recent onset, and
      samples of the normal population were compared. RESULTS: In all cases the disease
      showed a self limiting arthritis and overall good prognosis. The diagnostic
      ability of a combination of four clinical features--symmetrical ankle arthritis,
      symptoms of less than two months, age below 40 years, and erythema nodosum--was
      exceptionally high. When test positivity is defined as the presence of at least
      three of four criteria the set rendered a sensitivity of 93%, a specificity of
      99%, a positive predictive value of 75%, and a negative predictive value of
      99.7%. The disease clustered in the months March-July. The disease was negatively
      associated with smoking (odds ratio (OR) 0.09; 95% confidence interval (95% CI)
      0.02 to 0.37) and positively associated with the presence of the DQ2 (DQB1*0201)
      DR3 (DRB1*0301) haplotype (OR 12.33; 95% CI 5.97 to 25.48). CONCLUSION: The
      disease entity acute sarcoid arthritis has highly diagnostic clinical features.
      The seasonal clustering, the protective effect of smoking, and the association
      with specific HLA class II antigens support the hypothesis that it results from
      exposure of susceptible hosts to environmental agents through the lungs.

PMID- 12006322
TI  - Comparative study of different enzyme immunoassays for measurement of IgM and IgA
      rheumatoid factors.
AB  - OBJECTIVE: To compare the value of various IgM and IgA rheumatoid factor (RF)
      tests for the diagnosis of rheumatoid arthritis (RA). METHODS: Firstly, the latex
      test, one global assay (for IgM, IgA, and IgG RF), six IgM, and four IgA RF
      assays were compared in a particularly challenging situation-that is, with 67
      patients with RA, many of whom were latex negative, and 91 non-RA controls, many
      of whom were latex positive. More detailed evaluation followed with three IgM RF
      tests (two commercially available kits and one assay developed in our laboratory)
      and two IgA RF tests (one commercially available and one from our laboratory) in
      two more representative samples of rheumatological patients (146 RA and 75 non-RA
      controls). RESULTS: Diagnostic performance differed considerably between the
      assays. For IgM RF detection the highest sensitivity (88%) was obtained with the
      Diamedix kit (specificity 67%) and for IgA RF with the Inova kit (sensitivity
      65%, specificity 88%). Combining one IgM and one IgA RF test improved diagnostic
      performance when both tests were in agreement, but at the cost of yielding 15-27%
      of discrepant results which did not help in ruling RA in or out. Mean
      concentration values differed significantly among IgM RF tests, and in most cases
      concentrations were not correlated. CONCLUSIONS: Available tests for IgM RF
      isotype vary in accuracy, and none is uniformly better than all the others. For
      IgA RF isotype, the Inova kit appears to be the best. Quantitative results cannot
      be compared across tests. Combination of one IgM and one IgA RF test may improve
      diagnostic accuracy.

PMID- 12006323
TI  - Long term efficacy and safety of cyclosporin versus parenteral gold in early
      rheumatoid arthritis: a three year study of radiographic progression, renal
      function, and arterial hypertension.
AB  - OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and
      parenteral gold in the treatment of early, active, severe rheumatoid arthritis
      (RA), and to study the reversibility of cyclosporin associated renal dysfunction
      in patients who discontinued cyclosporin treatment. METHODS: The patients
      continued to receive cyclosporin or parenteral gold in an 18 month open extension
      to an 18 month randomised, parallel group study. The main efficacy variable was
      blinded evaluation of radiographic progression of joint damage. Safety variables
      included serum creatinine, calculated creatinine clearance, and blood pressure.
      RESULTS: Radiographic progression during follow up was similar in both groups.
      About 60% of the patients in the intention to treat groups (n=272) and about half
      of the patients in the completer groups (n=114) had definite radiographic
      progression in joint damage (increases >6 in the Larsen-Dale score), and about
      one in three also had substantial progression (>18 increase in Larsen-Dale
      score). Both systolic and diastolic blood pressure were significantly increased
      in the cyclosporin group compared with the gold group, and 12/139 (9%) versus
      3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine
      increased by 28% at the treatment end point in the cyclosporin group as compared
      with 7% in the gold group. The mean calculated creatinine clearance was reduced
      by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at
      the end of the study. At the final follow up visit after discontinuation of
      cyclosporin (at least three months after treatment was stopped) the mean serum
      creatinine was increased by 15% and creatinine clearance reduced by 16%.
      Sustained increases in serum creatinine at this post-treatment end point were
      mostly seen in patients with a raised serum creatinine during treatment of at
      least 50%. CONCLUSION: Three year changes in radiographic damage during
      cyclosporin and parenteral gold were similar in patients with early, active RA.
      Abnormal renal function and raised blood pressure were often seen in the
      cyclosporin treated patients.

PMID- 12006324
TI  - Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra
      articular feature of rheumatoid arthritis (RA). Features that predict progression
      of FA in patients with RA have not yet been determined. OBJECTIVE: To identify
      clinical features that predict progressive FA in patients with RA. METHODS: An
      unselected cohort of 29 patients with RA and FA confirmed by high resolution
      computed tomography (HRCT) were studied prospectively for 24 months. Three
      monthly clinical assessment, four monthly pulmonary function tests, and yearly
      HRCT scanning was undertaken on these patients. Progressive FA was defined as
      >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing
      FA on HRCT or death as a result of FA. RESULTS: During 24 months of follow up
      10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute
      ground glass exacerbations or increasing reticular pattern lung involvement.
      Progressive FA was associated with the presence of bibasal crackles (p=0.041),
      TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung
      involvement on HRCT at initial presentation. When multiple logistic regression
      was used, only TLCO remained significant. Receiver operator curve analysis was
      employed to identify presenting TLCO of progressive FA. A TLCO <54% of the
      predicted value demonstrated 80% sensitivity and 93% specificity in predicting
      progressive FA. CONCLUSIONS: A TLCO <54% of the predicted value is a highly
      specific predictor of disease progression.

PMID- 12006325
TI  - Neutrophil CD64 expression: distinguishing acute inflammatory autoimmune disease
      from systemic infections.
AB  - BACKGROUND: Common bacterial and opportunistic infections are a major cause of
      mortality in patients who are immunosuppressed owing to treatment with
      corticosteroids or cytotoxic drugs. Common laboratory tests for infection lack
      sensitivity and specificity. One of the new generation of tests to detect early
      systemic infections measures the up regulation of an Fc receptor (Fcgamma R1, or
      CD64) on neutrophils. The Fc receptors on white blood cells are very important
      for effective phagocytosis of bacteria and are up regulated during an infection.
      OBJECTIVE: To measure the clinical usefulness of quantitative CD64 measurements
      to differentiate between systemic infection and active autoimmune inflammation in
      an ongoing study. METHODS: Patients with systemic infection (n=27), active
      autoimmune inflammatory disease (n=44), vasculitis (n=5), and controls (n=20)
      were studied for neutrophil CD64 expression using monoclonal antibodies and flow
      cytometry. RESULTS: The median (interquartile range (IQR)) CD64 expression in
      patients with active inflammatory disease and systemic infection was 907.5 (586
      1550) and 3647 (2380-6642), respectively (p<0.0001). The median (IQR) CD64
      expression in control patients (osteoarthritis and fibromyalgia) was 505 (359
      599). The sensitivity and specificity of CD64 expression on neutrophils to
      diagnose systemic infection (using a cut off value of 2000) was 85% and 91%,
      respectively. CONCLUSION: These results indicate that quantitative measurement of
      CD64 can distinguish between systemic infection and the flare of autoimmune
      diseases.

PMID- 12006326
TI  - Magnetic resonance imaging in the diagnosis and follow up of Takayasu's arteritis
      in children.
AB  - BACKGROUND: Takayasu's arteritis (TA) has a mortality rate of up to 40% in
      children. Because the clinical presentation of TA is often non-specific, accurate
      and prompt diagnosis depends on a high degree of awareness and appropriate
      laboratory and imaging studies. OBJECTIVE: To examine the use of advanced
      magnetic resonance imaging (MRI) in evaluating, gauging activity, and following
      the complications of TA. METHODS AND RESULTS: T1 weighted, T2 weighted, contrast
      enhanced MR images, and MR angiograms of the chest and abdomen were obtained in
      three children (age range 11-14 years). The MRI studies confirmed the diagnosis
      of active TA and were repeated to evaluate response to treatment. Two patients
      showed complete resolution of lesions found on MRI at six and 12 months' follow
      up, while the third patient showed no significant improvement. CONCLUSION: MRI
      can be used to help establish the initial diagnosis of TA in children, and it can
      also be used to monitor disease activity and to guide treatment.

PMID- 12006327
TI  - Effect of bisphosphonates on cartilage turnover assessed with a newly developed
      assay for collagen type II degradation products.
AB  - BACKGROUND: Animal studies of arthritis have suggested that bisphosphonates may
      have chondroprotective abilities. OBJECTIVE: To evaluate the effect of
      bisphosphonate treatment on cartilage degradation. METHODS: Type II collagen is
      almost exclusively localised in cartilage, where it is the major structural
      component of the tissue. Hence fragments derived from this protein should
      represent a specific index for cartilage degradation. The urinary concentration
      of collagen type II C-telopeptide degradation products (CTX-II) was measured by a
      new immunoassay (enzyme linked immunosorbent assay (ELISA)). The serum
      concentration of collagen type I C-telopeptide degradation products (CTX-I), a
      marker of bone degradation, was also measured by ELISA. PARTICIPANTS: Two groups
      were studied. The alendronate group included 63 healthy postmenopausal women aged
      45-54 randomly allocated to receive three years' treatment with 1 mg, 5 mg, 10
      mg, or 20 mg alendronate daily or placebo. In the third year the women receiving
      20 mg were switched to placebo. The ibandronate group included 119 women at least
      10 years after the menopause aged <75 randomly allocated to receive 12 months'
      treatment with 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg ibandronate daily or
      placebo followed by 12 months without treatment. RESULTS: 20 mg of alendronate
      and 2.5 and 5 mg of ibandronate treatment produced significant decreases in
      urinary CTX-II to about 50% of baseline. The level reached after three months of
      treatment remained practically constant during the following 12-36 treatment
      months. When treatment was withdrawn CTX-II values returned towards baseline.
      Serum CTX-I also decreased rapidly within three months, but to a level of about
      30% of baseline. CONCLUSIONS: The urinary excretion of CTX-II, a new marker of
      cartilage degradation, decreases significantly in response to bisphosphonate.
      This suggests that bisphosphonates may have chondroprotective effects in humans.
      By measurement of CTX-II it should be possible to monitor the effects of drugs
      that potentially inhibit cartilage destruction.

PMID- 12006328
TI  - Histological assessment of the early enthesitis lesion in spondyloarthropathy.
AB  - OBJECTIVES: To describe the histological changes in acute enthesopathy in early
      spondyloarthropathies (SpA). METHODS: Clinically evident acute enthesopathy was
      confirmed by magnetic resonance imaging and ultrasonography in four cases of
      plantar fasciitis and one case of patellar tendon enthesitis. Ultrasound guided
      biopsy of insertional points was carried out with a Jamshedi needle. Control
      tissue was obtained from two subjects undergoing spinal grafting surgery.
      Standard histochemistry and immunohistochemistry analysis using the avidin-biotin
      immunoperoxidase complex method employing markers against CD3, CD8, CD34, and
      CD68 was used to determine cellular infiltrates at the insertion point. RESULTS:
      The enthesis architecture was abnormal in the SpA group, with increased
      vascularity and cellular infiltration compared with normal subjects. The
      predominant infiltrating cell at the enthesis fibrocartilage was the macrophage,
      but there was a paucity of lymphocytes at the insertion point. CONCLUSION: These
      preliminary findings have implications for a better understanding of the
      pathology in early SpA.

PMID- 12006329
TI  - FasL autoantibodies in vasculitis are associated with the presence of anticorneal
      epithelial antibodies.

PMID- 12006330
TI  - Poor accuracy and interobserver reliability of knee arthroscopy measurements are
      improved by the use of variable angle elongated probes.
AB  - OBJECTIVES: (a)To determine the accuracy and reliability of arthroscopic
      measurements of cartilage lesion diameter in an artificial right knee model; (b)
      to determine whether the use of a set of variable angle elongated probes improves
      performance; and (c) to identify other sources of variability. METHODS: Ovoid
      "lesions" were drawn on the five cartilage surfaces of four plastic knees models.
      Two observers assessed these 20 lesions arthroscopically, measuring two diameters
      in orientations parallel and orthogonal to the probe. Observer 1 (orthopaedic
      surgeon) and observer 2 (arthroscopic rheumatologist) made two sets of
      measurements, firstly with the conventional probe and five months later with the
      variable angle elongated (VAE) probes. The knees were disarticulated to determine
      true lesion diameter. RESULTS: Observer 1 had negligible bias and good accuracy
      regardless of orientation or probe type. Observer 2 demonstrated both bias and
      poor accuracy using the conventional probe. Both improved using VAE probes. Poor
      interobserver reliability with conventional probes also improved using VAE
      probes. Major sources of variability could be traced to the probe type, the
      characteristics of the operator, and the orientation of the lesion in relation to
      the probe; the lesion location itself did not cause variability. CONCLUSIONS:
      Variation in accuracy and poor interobserver reliability of measurements with
      conventional methods of cartilage lesion diameter measurement improved when
      specially designed measurement probes were used. Arthroscopic measurements
      performed as well as most clinical and radiographic measures. These findings have
      important implications for the use of arthroscopy as an outcome in multicentre
      trials where arthroscopists have different levels of experience.

PMID- 12006331
TI  - Myositis and swollen knees: disease or treatment complication?
AB  - Interesting and unusual causes of knee pain in three patients with idiopathic
      inflammmatory myositis seen in the clinic over the past 12 months are reported.
      Their clinical features are described and treatment discussed emphasising the
      importance of being able to differentiate between a manifestation of the
      rheumatic disease and a treatment complication. Publications on this topic are
      also reviewed.

PMID- 12006332
TI  - Acute abdominal pain in systemic lupus erythematosus: focus on lupus enteritis
      (gastrointestinal vasculitis).
AB  - OBJECTIVE: To determine the causes of acute abdominal pain in systemic lupus
      erythematosus (SLE) and to compare the clinical and laboratory data, especially
      antiphospholipid antibodies and the SLE Disease Activity Index (SLEDAI), between
      lupus enteritis (gastrointestinal vasculitis) and acute abdominal pain without
      lupus enteritis in patients with SLE. METHODS: A retrospective study was carried
      out for all patients admitted with SLE from 1993 to March 2001. The SLEDAI and
      laboratory data were collected at the time of diagnosis of SLE and at the time of
      acute abdominal pain. Lupus enteritis (gastrointestinal vasculitis) was diagnosed
      by clinical investigation and abdominal computed tomographic findings. RESULTS:
      Chart review identified 175 patients (20 male, 155 female) who had been admitted
      with SLE. Of these patients, 38 (22%) presented with acute abdominal pain. Lupus
      enteritis was the most common cause of acute abdominal pain. Patients were
      divided into three groups: group 1: lupus enteritis (n=17), group 2: acute
      abdominal pain without lupus enteritis (n=21), and group 3: SLE without acute
      abdominal pain (n=137). There was no difference in age and sex among the three
      groups. Antiphospholipid, anti-RNP, anti-Sm, anti-Ro, and anti-La antibodies did
      not differ among the three groups. There was no difference in the SLEDAI at the
      time of diagnosis and at the time of acute abdominal pain between groups 1 and 2.
      Complement, erythrocyte sedimentation rate, C reactive protein, and anti-dsDNA
      measured at the time of acute abdominal pain did not differ between groups 1 and
      2. A drop in the white blood cell count at the time of abdominal pain was more
      prominent in group 1 than group 2. In lupus enteritis, the jejunum and ileum were
      the sites most commonly affected. Rectal involvement was rare. Even though four
      patients relapsed, all the patients with lupus enteritis, including those who
      relapsed, responded well to corticosteroid. CONCLUSION: Lupus enteritis is the
      most common cause of acute abdominal pain in SLE. All patients with lupus
      enteritis responded well to a high dose of a corticosteroid without surgical
      intervention. The SLEDAI and laboratory data, except leucopenia, do not correlate
      with the occurrence of lupus enteritis.

PMID- 12006333
TI  - Prevalence of spondyloarthritis in Terceira, Azores: a population based study.
AB  - OBJECTIVE: To determine the prevalence of spondyloarthritis (SpA) in the
      Caucasian population of Terceira Island, Azores. METHODS: Study subjects were
      recruited from people over the age of 50 years from one half of the island of
      Terceira (n=24 561). Seventy eight men and 78 women from each five year age group
      were selected, giving a total of 468 men and 468 women available for study, of
      whom 490 agreed to take part. These subjects were assessed by dorsal, lumbar, and
      pelvic radiography. Radiological sacroiliitis was identified in eight patients on
      whom sacroiliac computed tomography scans were performed. HLA class I typing by
      polymerase chain reaction with sequence-specific primers was carried out in seven
      cases. RESULTS: SpA was present in eight subjects (1.6%, 95% CI 0.8 to 2.7%),
      including seven men (2.7%) and one woman (0.4%). Three (1.2% ) male patients with
      definite ankylosing spondylitis were HLA-B27 positive. Only one person had a
      previous diagnosis of SpA. CONCLUSION: These data complement previous studies in
      European countries on SpA prevalence and establish an estimate of the overall
      prevalence of SpA in a southern European population.

PMID- 12006334
TI  - Classification criteria for Sjogren's syndrome: a revised version of the European
      criteria proposed by the American-European Consensus Group.
AB  - Classification criteria for Sjogren's syndrome (SS) were developed and validated
      between 1989 and 1996 by the European Study Group on Classification Criteria for
      SS, and broadly accepted. These have been re-examined by consensus group members,
      who have introduced some modifications, more clearly defined the rules for
      classifying patients with primary or secondary SS, and provided more precise
      exclusion criteria.

PMID- 12006335
TI  - Safety and efficacy of TNFalpha blockade in relapsing vasculitis.

PMID- 12006336
TI  - Anti-tumour necrosis factor monoclonal antibody treatment for ocular Behcet's
      disease.

PMID- 12006337
TI  - Is hirudin a potential therapeutic agent for arthritis?

PMID- 12006338
TI  - Steroid induced psychosis in systemic lupus erythematosus: a possible role of
      serum albumin level.

PMID- 12006339
TI  - Autoantibodies against C1q: view on association between systemic lupus
      erythematosus disease manifestation and C1q autoantibodies.

PMID- 12006340
TI  - Silent thyroiditis associated with etanercept in rheumatoid arthritis.

PMID- 12006341
TI  - Synovial T cell proliferation to the Yersinia enterocolitica 19 kDa antigen
      differentiates yersinia triggered reactive arthritis (ReA) from ReA triggered by
      other enterobacteria.

PMID- 12006342
TI  - Leflunomide and hypertension.

PMID- 12006343
TI  - Adhesion molecule expression in the synovial membrane of psoriatic arthritis.

PMID- 12006344
TI  - Headache as the initial presentation of Wegener's granulomatosis.

PMID- 12006345
TI  - Extremely high dose pravastatin may suppress amyloidogenesis in a mouse model.

PMID- 12006346
TI  - Long acting somatostatin analogue for the treatment of refractory RA.

PMID- 12006347
TI  - Muscle fiber type is associated with obesity and weight loss.
AB  - The purpose of this study was to test the hypothesis that muscle fiber type is
      related to obesity. Fiber type was compared 1) in lean and obese women, 2) in
      Caucasian (C) and African-American (AA) women, and 3) in obese individuals who
      lost weight after gastric bypass surgery. When lean (body mass index 24.0 +/- 0.9
      kg/m(2), n = 28) and obese (34.8 +/- 0.9 kg/m(2), n = 25) women were compared,
      there were significant (P < 0.05) differences in muscle fiber type. The obese
      women possessed fewer type I (41.5 +/- 1.8 vs. 54.6 +/- 1.8%) and more type IIb
      (25.1 +/- 1.5 vs. 14.4 +/- 1.5%) fibers than the lean women. When ethnicity was
      accounted for, the percentage of type IIb fibers in obese AA was significantly
      higher than in obese C (31.0 +/- 2.4% vs. 19.2 +/- 1.9%); fewer type I fibers
      were also found in obese AA (34.5 +/- 2.8% vs. 48.6 +/- 2.2%). These data are
      consistent with the higher incidence of obesity and greater weight gain reported
      in AA women. With weight loss intervention, there was a positive relationship (r
      = 0.72, P < 0.005) between the percentage of excess weight loss and the
      percentage of type I fibers in morbidly obese patients. These findings indicate
      that there is a relationship between muscle fiber type and obesity.

PMID- 12006348
TI  - Overexpression of CRIP in transgenic mice alters cytokine patterns and the immune
      response.
AB  - Cysteine-rich intestinal protein (CRIP), which contains a double zinc finger
      motif, is a member of the Group 2 LIM protein family. Our results showed that the
      developmental regulation of CRIP in neonates was not influenced by conventional
      vs. specific pathogen-free housing conditions. Thymic and splenic CRIP expression
      was not developmentally regulated. A line of transgenic (Tg) mice that
      overexpress the rat CRIP gene was created. When challenged with
      lipopolysaccharide, the Tg mice lost more weight, exhibited increased mortality,
      experienced greater diarrhea incidence, and had less serum interferon-gamma (IFN
      gamma) and more interleukin (IL)-6 and IL-10. Similarly, splenocytes from the Tg
      mice produced less IFN-gamma and IL-2 and more IL-10 and IL-6 upon mitogen
      stimulation. Delayed-type hypersensitivity response was less in the Tg mice.
      Influenza virus infection produced greater weight loss in the Tg mice, which also
      showed delayed viral clearance. The observed responses to overexpression of the
      CRIP gene are consistent with a role for this LIM protein in a cellular pathway
      that produces an imbalance in cytokine pattern favoring Th2 cytokines.

PMID- 12006349
TI  - Inhibition of glycogen synthesis by fatty acid in C(2)C(12) muscle cells is
      independent of PKC-alpha, -epsilon, and -theta.
AB  - We have previously shown that glycogen synthesis is reduced in lipid-treated
      C(2)C(12) skeletal muscle myotubes and that this is independent of changes in
      glucose uptake. Here, we tested whether mitochondrial metabolism of these lipids
      is necessary for this inhibition and whether the activation of specific protein
      kinase C (PKC) isoforms is involved. C(2)C(12) myotubes were pretreated with
      fatty acids and subsequently stimulated with insulin for the determination of
      glycogen synthesis. The carnitine palmitoyltransferase-1 inhibitor etomoxir, an
      inhibitor of beta-oxidation of acyl-CoA, did not protect against the inhibition
      of glycogen synthesis caused by the unsaturated fatty acid oleate. In addition,
      although oleate caused translocation, indicating activation, of individual PKC
      isoforms, inhibition of PKC by pharmacological agents or adenovirus-mediated
      overexpression of dominant negative PKC-alpha, -epsilon, or -theta mutants was
      unable to prevent the inhibitory effects of oleate on glycogen synthesis. We
      conclude that neither mitochondrial lipid metabolism nor activation of PKC-alpha,
      -epsilon, or -theta plays a role in the direct inhibition of glycogen synthesis
      by unsaturated fatty acids.

PMID- 12006350
TI  - Glucose transport rate and glycogen synthase activity both limit skeletal muscle
      glycogen accumulation.
AB  - We varied rates of glucose transport and glycogen synthase I (GS-I) activity (%GS
      I) in isolated rat epitrochlearis muscle to examine the role of each process in
      determining the rate of glycogen accumulation. %GS-I was maintained at or above
      the fasting basal range during 3 h of incubation with 36 mM glucose and 60
      microU/ml insulin. Lithium (2 mM LiCl) added to insulin increased glucose
      transport rate and muscle glycogen content compared with insulin alone. The
      glycogen synthase kinase-3beta inhibitor GF-109203 x (GF; 10 microM) maintained
      %GS-I about twofold higher than insulin with or without lithium but did not
      increase glycogen accumulation. When %GS-I was lowered below the fasting range by
      prolonged incubation with 36 mM glucose and 2 mU/ml insulin, raising rates of
      glucose transport with bpV(phen) or of %GS-I with GF produced additive increases
      in glycogen concentration. Phosphorylase activity was unaffected by GF or
      bpV(phen). In muscles of fed animals, %GS-I was approximately 30% lower than in
      those of fasted rats, and insulin-stimulated glycogen accumulation did not occur
      unless %GS-I was raised with GF. We conclude that the rate of glucose transport
      is rate limiting for glycogen accumulation unless %GS-I is below the fasting
      range, in which case both glucose transport rate and GS activity can limit
      glycogen accumulation.

PMID- 12006351
TI  - Isotopomer spectral analysis of intermediates of cholesterol synthesis in human
      subjects and hepatic cells.
AB  - Steroid intermediates of the cholesterol synthesis pathway are characterized by
      rapid turnover rates relative to cholesterol due to their small pool size.
      Because the small pools will label rapidly, these intermediates may provide
      valuable information about the incorporation of isotopes in de novo synthesis of
      cholesterol and related compounds. The labeling of cholesterol synthesis
      intermediates from [1-(13)C]acetate was investigated in human subjects and in
      liver cell models by means of isotopomer spectral analysis (ISA). In human
      subjects, infusing [1-(13)C]acetate into the duodenum for 12 h demonstrated that
      approximately 50% of the plasma lathosterol pool was derived from de novo
      synthesis during this interval. The lipogenic acetyl-CoA precursor pool
      enrichment reached a constant value within 3 h of the start of the infusion. In
      vitro studies indicated that liver cell models decrease de novo lathosterol
      synthesis when cholesterol synthesis is inhibited by statins or cholesterol
      containing serum. We propose a new calculation to increase the accuracy and
      precision of cholesterol synthesis estimates in vivo combining the ISA of
      lathosterol and cholesterol.

PMID- 12006352
TI  - Long-term high-fat feeding leads to severe insulin resistance but not diabetes in
      Wistar rats.
AB  - Although lipid excess can impair beta-cell function in vitro, short-term high-fat
      feeding in normal rats produces insulin resistance but not hyperglycemia. This
      study examines the effect of long-term (10-mo) high polyunsaturated fat feeding
      on glucose tolerance in Wistar rats. The high fat-fed compared with the chow-fed
      group was 30% heavier and 60% fatter, with approximately doubled fasting
      hyperinsulinemia (P < 0.001) but only marginal fasting hyperglycemia (7.5 +/- 0.1
      vs. 7.2 +/- 0.1 mmol/l, P < 0.01). Insulin sensitivity was approximately 67%
      lower in the high-fat group (P < 0.01). The acute insulin response to intravenous
      arginine was approximately double in the insulin-resistant high-fat group (P <
      0.001), but that to intravenous glucose was similar in the two groups. After the
      intravenous glucose bolus, plasma glucose decline was slower in the high fat-fed
      group, confirming mild glucose intolerance. Therefore, despite severe insulin
      resistance, there was only a mildly elevated fasting glucose level and a relative
      deficiency in glucose-stimulated insulin secretion; this suggests that a genetic
      or congenital susceptibility to beta-cell impairment is required for overt
      hyperglycemia to develop in the presence of severe insulin resistance.

PMID- 12006353
TI  - Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal
      muscle but not adipocytes.
AB  - 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) reportedly activates AMP
      activated protein kinase (AMPK) and stimulates glucose uptake by skeletal muscle
      cells. In this study, we investigated the role of AMPK in AICAR-induced glucose
      uptake by 3T3-L1 adipocytes and rat soleus muscle cells by overexpressing wild
      type and dominant negative forms of the AMPKalpha2 subunit by use of adenovirus
      mediated gene transfer. Overexpression of the dominant negative mutant had no
      effect on AICAR-induced glucose transport in adipocytes, although AMPK activation
      was almost completely abolished. This suggests that AICAR-induced glucose uptake
      by 3T3-L1 adipocytes is independent of AMPK activation. By contrast,
      overexpression of the dominant negative AMPKalpha2 mutant in muscle markedly
      suppressed both AICAR-induced glucose uptake and AMPK activation, although
      insulin-induced uptake was unaffected. Overexpression of the wild-type AMPKalpha2
      subunit significantly increased AMPK activity in muscle but did not enhance
      glucose uptake. Thus, although AMPK activation may not, by itself, be sufficient
      to increase glucose transport, it appears essential for AICAR-induced glucose
      uptake in muscle.

PMID- 12006354
TI  - Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17beta
      D-glucuronide in rats.
AB  - The gender difference in the urinary excretion of estradiol-17beta-glucuronide
      (E(2)-17betaG) was examined in rats. The urinary clearance of E(2)-17betaG was
      >250 times lower in male than in female rats. No such major gender difference was
      observed in its biliary excretion or metabolism in kidney homogenate. Both plasma
      protein binding and inulin clearance were comparable in male and female rats,
      suggesting that this gender difference cannot be explained by glomerular
      filtration. The urinary clearance with respect to the plasma unbound E(2)-17betaG
      in male rats was <1% of the glomerular filtration rate, indicating its potential
      reabsorption by the kidney, and this increased to a level comparable with that
      found in female rats when dibromosulfophthalein was coinfused. A marked increase
      in E(2)-17betaG urinary excretion was also observed in male rats that had
      undergone orchidectomy. Testosterone injections given to female rats reduced the
      urinary excretion to a level comparable with that of control male rats. The
      concomitant change in the expression of the gene product for organic anion
      transporting polypeptide Oatp1, of which E(2)-17betaG is a typical substrate, was
      found in the kidney membrane fractions after these treatments. These results
      suggest that urinary E(2)-17betaG excretion is subject to hormonal regulation and
      that the large gender difference can be explained by regulation in Oatp1-mediated
      reabsorption.

PMID- 12006355
TI  - Dual actions of lanthanides on ACTH-inhibited leak K(+) channels.
AB  - Bovine adrenal zona fasciculata cells express background K(+) channels (I(AC)
      channels) whose activity is potently inhibited by ACTH. In whole cell patch clamp
      recordings, it was discovered that the trivalent lanthanides (Ln(3+)s) lanthanum
      and ytterbium interact with two binding sites to modulate K(+) flow through these
      channels. Despite large differences in ionic radii, these Ln(3+)s inhibited I(AC)
      channels half-maximally with IC(50) values near 50 microM. In addition, these
      Ln(3+)s blocked and reversed ACTH-mediated inhibition of I(AC) K(+) channels at
      similar concentrations. The Ln(3+)s did not alter inhibition of I(AC) by
      angiotensin II or cAMP. Ln(3+)-induced uncoupling of ACTH receptor activation
      from I(AC) inhibition was prevented by raising the external Ca(2+) concentration
      from 2 to 10 mM. The divalent cation Ni(2+) (500 microM) also blocked ACTH
      dependent inhibition of I(AC) through a Ca(2+)-sensitive mechanism. The results
      are consistent with a model in which Ln(3+)s produce opposing actions on I(AC)
      K(+) currents through two separate binding sites. In addition to directly
      inhibiting I(AC), Ln(3+)s (and Ni(2+)) bind with high affinity to a Ca(2+)
      selective site associated with the ACTH receptor. By displacing Ca(2+) from this
      site, Ln(3+)s prevent ACTH from binding and accelerate its dissociation. These
      results identify Ln(3+)s as a relatively potent group of noncompetitive ACTH
      receptor antagonists. Allosteric actions of trivalent and divalent metal cations
      on hormone binding, mediated through Ca(2+)-specific sites, may be common to a
      variety of peptide hormone receptors.

PMID- 12006356
TI  - Decreased insulin action in skeletal muscle from patients with McArdle's disease.
AB  - Insulin action is decreased by high muscle glycogen concentrations in skeletal
      muscle. Patients with McArdle's disease have chronic high muscle glycogen levels
      and might therefore be at risk of developing insulin resistance. In this study,
      six patients with McArdle's disease and six matched control subjects were
      subjected to an oral glucose tolerance test and a euglycemic-hyperinsulinemic
      clamp. The muscle glycogen concentration was 103 +/- 45% higher in McArdle
      patients than in controls. Four of six McArdle patients, but none of the
      controls, had impaired glucose tolerance. The insulin-stimulated glucose
      utilization and the insulin-stimulated increase in glycogen synthase activity
      during the clamp were significantly lower in the patients than in controls (51.3
      +/- 6.0 vs. 72.6 +/- 13.1 micromol x min(-1) x kg lean body mass(-1), P < 0.05,
      and 53 +/- 15 vs. 79 +/- 9%, P < 0.05, n = 6, respectively). The difference in
      insulin-stimulated glycogen synthase activity between the pairs was significantly
      correlated (r = 0.96, P < 0.002) with the difference in muscle glycogen level.
      The insulin-stimulated increase in Akt phosphorylation was smaller in the McArdle
      patients than in controls (45 +/- 13 vs. 76 +/- 13%, P < 0.05, respectively),
      whereas basal and insulin-stimulated glycogen synthase kinase 3alpha and protein
      phosphatase-1 activities were similar in the two groups. Furthermore, the ability
      of insulin to decrease and increase fat and carbohydrate oxidation, respectively,
      was blunted in the patients. In conclusion, these data show that patients with
      McArdle's glycogen storage disease are insulin resistant in terms of glucose
      uptake, glycogen synthase activation, and alterations in fuel oxidation. The data
      further suggest that skeletal muscle glycogen levels play an important role in
      the regulation of insulin-stimulated glycogen synthase activity.

PMID- 12006357
TI  - Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to
      endotoxin in humans.
AB  - Type 2 diabetes is associated with biochemical evidence of low-grade
      inflammation, and experimental studies have suggested that both insulin and
      glucose affect inflammatory responses. To determine the effect of in vivo changes
      in glucose availability and plasma insulin concentrations in humans, we
      administered 20 U/kg Escherichia coli lipopolysaccharide (LPS) or saline
      (control) to 14 subjects during a euglycemic hyperinsulinemic clamp (n = 6) or an
      infusion of sterile saline (n = 8). Parallel in vitro studies on human whole
      blood were undertaken to determine whether there was a direct effect of glucose,
      insulin, and leptin on proinflammatory cytokine production. Infusion of glucose
      and insulin significantly amplified and/or prolonged the cardiovascular, plasma
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and
      counterregulatory hormone responses to LPS, whereas the effects on fever, plasma
      norepinephrine concentrations, and oxygen consumption were unaffected. In vitro
      studies showed no modulation of LPS-stimulated IL-6 or TNF-alpha production by
      glucose, insulin, or leptin at physiologically relevant concentrations.
      Hyperinsulinemia indirectly enhances key components of the systemic inflammatory
      and stress responses in this human model of infection.

PMID- 12006358
TI  - Type 2 diabetic patients may have a mild form of an injury response: a clinical
      research center study.
AB  - Patients with type 2 diabetes (DM) demonstrate inadequate insulin release,
      elevated gluconeogenesis, and diminished nonoxidative glucose disposal. Similar
      metabolic changes occur during systemic injury caused by infection, trauma, or
      cancer. Described here are metabolic changes occurring in 16 DM and 11 lung
      cancer patients (CA) and 13 normal volunteers (NV). After a 10-h overnight fast,
      all subjects had fasting hormone and substrate concentrations determined, along
      with rates of glucose production, leucine appearance (LA), and leucine oxidation
      (LO). Fasting insulin (data not shown) and C-peptide concentrations were elevated
      in DM and CA compared with weight-matched NV (0.72 +/- 0.09 and 0.64 +/- 0.08 vs.
      0.51 +/- 0.03 mg/l, P < 0.05). C-reactive protein concentration was elevated in
      CA compared with DM and NV (23.3 +/- 6.0 vs. 4.2 +/- 1.4 and 2.1 +/- 0.5 mg/l, P
      < 0.01). All counterregulatory hormones were normal except for serum cortisol
      (11.4 +/- 1.0 and 12.1 +/- 1.0 vs. 8.9 +/- 0.7 microg/dl, DM and CA vs. NL,
      respectively, P < 0.05). Glucose production was increased in DM and CA compared
      with NV (4.22 +/- 0.6 and 3.53 +/- 0.3 vs. 2.76 +/- 0.2 mg x kg lean body wt(-1)
      x min(-1), P < 0.01). LO and LA were increased in DM and CA compared with NV (LO:
      27.3 +/- 1.5 and 19.7 +/- 1.5 vs. 12.5 +/- 1.1 mmol x kg lean body wt(-1) x min(
      1), P < 0.05; LA: 91.9 +/- 6.6 and 90.7 +/- 7.0 vs. 79.1 +/- 6.0 mmol. kg lean
      body wt(-1) x min(-1), P < 0.01). DM share similar metabolic derangements with
      CA. The increase in LA may be secondary to an increased glucose production where
      amino acids are mobilized to provide the liver with adequate substrate to make
      glucose. The increase in glucose production may also be part of the injury
      response, or it may represent a form of insulin resistance that exists in both
      the DM and (non-DM) CA patients.

PMID- 12006359
TI  - Effect of fiber type and nutritional state on AICAR- and contraction-stimulated
      glucose transport in rat muscle.
AB  - AMP-activated protein kinase (AMPK) may mediate the stimulatory effect of
      contraction and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on glucose
      transport in skeletal muscle. In muscles with different fiber type composition
      from fasted rats, AICAR increased 2-deoxyglucose transport and total AMPK
      activity approximately twofold in epitrochlearis (EPI), less in flexor digitorum
      brevis, and not at all in soleus muscles. Contraction increased both transport
      and AMPK activity more than AICAR did. In EPI muscles, the effects of AICAR and
      contractions on glucose transport were partially additive despite a lower AMPK
      activity with AICAR compared with contraction alone. In EPI from fed rats,
      glucose transport responses were smaller than what was seen in fasted rats, and
      AICAR did not increase transport despite an increase in AMPK activity. AICAR and
      contraction activated both alpha(1)- and alpha(2)-isoforms of AMPK. Expression of
      both isoforms varied with fiber types, and alpha(2) was highly expressed in
      nuclei. In conclusion, AICAR-stimulated glucose transport varies with muscle
      fiber type and nutritional state. AMPK is unlikely to be the sole mediator of
      contraction-stimulated glucose transport.

PMID- 12006360
TI  - Site and mechanism of action of dynorphin A-(1-13) and N-methyl-D-aspartate on
      ACTH release in fetal sheep.
AB  - Dynorphin A (Dyn A) stimulates the release of ACTH in fetal sheep, a response
      that involves N-methyl-D-aspartate (NMDA) receptors but not the secretogogues
      corticotropin-releasing hormone or arginine vasopressin. We now find that neither
      Dyn A-(1-13) (0.5 mg/kg, i.v.) nor NMDA (4 mg/kg, i.v.) elicits ACTH release in
      postnatal lambs. This led us to hypothesize that Dyn A-(1-13) and NMDA might act
      to release placental ACTH. However, the ability of Dyn A-(1-13), NMDA, and the
      kappa-opioid receptor agonist U-50488H (1 mg/kg, i.v.) to release ACTH was lost
      after either fetal hypophysectomy (n = 4) or hypothalamo-pituitary disconnection
      (n = 4). These results indicate that neither the placenta nor the fetal pituitary
      is the site of action for these agonists and suggest a hypothalamic or
      suprahypothalamic site of action. Furthermore, the release of ACTH by Dyn A-(1
      13) and NMDA was abolished after pretreatment with indomethacin, suggesting that
      they might cause the release of a prostanoid, possibly from the placenta, that
      subsequently acts at the hypothalamus or serves as a permissive factor in the
      action of Dyn A-(1-13) and NMDA at the hypothalamus.

PMID- 12006361
TI  - Anabolic action of insulin on skin wound protein is augmented by exogenous amino
      acids.
AB  - To investigate the metabolic basis of skin wound healing, we measured in
      anesthetized rabbits the responses of protein kinetics in scalded skin to insulin
      and amino acids. L-[ring-(13)C(6)]Phe was infused on the 7th day after the ear
      was scalded, and the scalded ear was used as an arteriovenous unit to reflect
      protein kinetics in skin wound. The ipsilateral carotid artery was clamped to
      control the wound blood flow within four- to fivefold the normal skin rate to
      measure the enrichment difference in the scalded ear during hyperaminoacidemia.
      Neither insulin (2.5 mU x kg(-1) x min(-1)) nor amino acid (2.5 mg x kg(-1) x
      min(-1)) infusion alone improved net protein balance in the skin wound. In
      contrast, combined infusion of insulin and amino acids increased the net protein
      balance in skin wound from -6.5 +/- 4.5 to 1.4 +/- 5.2 micromol x 100 g(-1) x h(
      1) (P < 0.01, control vs. insulin plus amino acids). We conclude that there is an
      interactive effect of insulin and sufficient amino acid supply on protein
      metabolism in skin wound, meaning that their combined anabolic effect is greater
      than the sum of their individual effects.

PMID- 12006362
TI  - Analyte flux through chronically implanted subcutaneous polyamide membranes
      differs in humans and rats.
AB  - The rat is commonly used to evaluate physiological responses of subcutaneous
      tissue to implanted devices. In vivo longevity of various devices and the
      biocompatibility of biomaterials depend on how adjacent tissue interacts. How
      closely the rat model predicts the human response has not been well
      characterized. The objective of this study was to compare rat and human
      subcutaneous foreign body responses by monitoring the biochemical environment at
      a polymer-tissue interface over 8 days using microdialysis. Polyamide
      microdialysis probes were implanted subcutaneously in humans and rats (n = 12).
      Daily microdialysis samples were analyzed for glucose, lactate, pyruvate,
      glycerol, and urea. Blood glucose was also monitored. Analyte concentrations
      differed significantly between rats and humans at the implant-tissue interface.
      There were also qualitative differences in the 8-day trends. For example, over 8
      days, microdialysate glucose increased two- to fourfold in humans but decreased
      in rats (P < 0.001). This study reveals profound physiological differences at
      material-tissue interfaces in rats and humans and highlights the need for caution
      when extrapolating subcutaneous rat biocompatibility data to humans.

PMID- 12006363
TI  - Localization and function of group III metabotropic glutamate receptors in rat
      pancreatic islets.
AB  - Pancreatic islets contain ionotropic glutamate receptors that can modulate
      hormone secretion. The purpose of this study was to determine whether islets
      express functional group III metabotropic glutamate (mGlu) receptors. RT-PCR
      analysis showed that rat islets express the mGlu8 receptor subtype. mGlu8
      receptor immunoreactivity was primarily displayed by glucagon-secreting alpha
      cells and intrapancreatic neurons. By demonstrating the immunoreactivities of
      both glutamate and the vesicular glutamate transporter 2 (VGLUT2) in these cells,
      we established that alpha-cells express a glutamatergic phenotype. VGLUT2 was
      concentrated in the secretory granules of islet cells, suggesting that glutamate
      might play a role in the regulation of glucagon processing. The expression of
      mGlu8 by glutamatergic cells also suggests that mGlu8 may function as an
      autoreceptor to regulate glutamate release. Pancreatic group III mGlu receptors
      are functional because mGlu8 receptor agonists inhibited glucagon release and
      forskolin-induced accumulation of cAMP in isolated islets, and (R,S)-cyclopropyl
      4-phosphonophenylglycine, a group III mGlu receptor antagonist, reduced these
      effects. Because excess glucagon secretion causes postprandial hyperglycemia in
      patients with type 2 diabetes, group III mGlu receptor agonists could be of value
      in the treatment of these patients.

PMID- 12006364
TI  - Gene expression profile of rat adipose tissue at the onset of high-fat-diet
      obesity.
AB  - Morbid obesity is the result of massive expansion of white adipose tissue (WAT)
      and requires recruitment of adipocyte precursor cells and their supporting
      infrastructure. To characterize the change in the expression profile of the
      preexisting WAT at the start of obesity, when adipocyte hypertrophy is present
      but hyperplasia is still minimal, we employed a cDNA subtraction screen for genes
      differentially expressed in epididymal fat pads harvested 1 wk after the start of
      a 60% fat diet. Ninety-six genes were upregulated by at least 50% above the WAT
      of control rats receiving a 4% fat diet. Of these genes, 30 had not previously
      been identified. Sixteen of the 96 genes, including leptin, adipocyte complement
      related protein 30 kDa, and resistin, were predicted to encode a signal peptide.
      Ten of the 16 had been previously identified in other tissues and implicated in
      cell growth, proliferation, differentiation, cell cycle control, and
      angiogenesis. One was a novel gene. Twenty-nine novel fragments were identified.
      Thus, at the onset of high-fat-diet-induced obesity in rats, adipose tissue
      increases its expression of factors previously implicated in the expansion of
      nonadipocyte tissues and of several uncharacterized novel factors. The only one
      of these thus far characterized functionally was found to promote lipogenesis.

PMID- 12006365
TI  - Mild streptozotocin diabetes in the Gottingen minipig. A novel model of moderate
      insulin deficiency and diabetes.
AB  - Nonrodent models of diabetes are needed for practical and physiological reasons.
      Induction of mild insulin-deficient diabetes was investigated in male Gottingen
      minipigs by use of streptozotocin (STZ) alone (75, 100, and 125 mg/kg) or 125
      mg/kg combined with pretreatment with nicotinamide (NIA; 0, 20, 67, 100, 150, and
      230 mg/kg). Use of NIA resulted in a less steep slope of the regression line
      between fasting plasma glucose and changing doses compared with STZ [-7.0 +/- 1.4
      vs. 29.7 +/- 7.0 mM. mg(-1). kg(-1), P < 0.0001]. Intermediate NIA doses induced
      moderate changes of glucose tolerance [glucose area under the curve increased
      from 940 +/- 175 to 1,598 +/- 462 mM. min, P < 0.001 (100 mg/kg) and from 890 +/-
      109 to 1,669 +/- 691 mM. min, P = 0.003 (67 mg/kg)] with reduced insulin
      secretion [1,248 +/- 602 pM. min after 16 days and 1,566 +/- 190 pM. min after 60
      days vs. 3,251 +/- 804 pM. min in normal animals (P < 0.001)] and beta-cell mass
      [5.5 +/- 1.4 mg/kg after 27 days and 7.9 +/- 4.1 mg/kg after 60 days vs. 17.7 +/-
      4.7 mg/kg in normal animals (P = 0.009)]. The combination of NIA and STZ provided
      a model characterized by fasting and especially postprandial hyperglycemia and
      reduced, but maintained, insulin secretion and beta-cell mass. This model holds
      promise as an important tool for studying the pathophysiology of diabetes and
      development of new pharmacological agents for treatment of the disease.

PMID- 12006366
TI  - Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor,
      NPY, and AgRP mRNA expression.
AB  - Some, but not all, fats are obesogenic. The aim of the present studies was to
      investigate the effects of changing type and amount of dietary fats on energy
      balance, fat deposition, leptin, and leptin-related neural peptides: leptin
      receptor, neuropeptide Y (NPY), agouti-related peptide (AgRP), and
      proopiomelanocortin (POMC), in C57Bl/6J mice. One week of feeding with a highly
      saturated fat diet resulted in ~50 and 20% reduction in hypothalamic arcuate NPY
      and AgRP mRNA levels, respectively, compared with a low-fat or an n-3 or n-6
      polyunsaturated high-fat (PUFA) diet without change in energy intake, fat mass,
      plasma leptin levels, and leptin receptor or POMC mRNA. Similar neuropeptide
      results were seen at 7 wk, but by then epididymal fat mass and plasma leptin
      levels were significantly elevated in the saturated fat group compared with low
      fat controls. In contrast, fat and leptin levels were reduced in the n-3 PUFA
      group compared with all other groups. At 7 wk, changing the saturated fat group
      to n-3 PUFA for 4 wk completely reversed the hyperleptinemia and increased
      adiposity and neuropeptide changes induced by saturated fat. Changing to a low
      fat diet was much less effective. In summary, a highly saturated fat diet induces
      obesity without hyperphagia. A regulatory reduction in NPY and AgRP mRNA levels
      is unable to effectively counteract this obesogenic drive. Equally high fat diets
      emphasizing PUFAs may even protect against obesity.

PMID- 12006367
TI  - Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic
      subjects.
AB  - The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty
      acid (FFA) and glucose metabolism were compared in eight control and eight type 2
      diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and
      0.5 mU x kg(-1) x min(-1)) clamp and a two-step euglycemic IGF-I (26 and 52 pmol
      x kg(-1) x min(-1)) clamp with [3-(3)H]glucose, [1-(14)C]palmitate, and indirect
      calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose
      disposal (R(d)) to a similar extent in control subjects. In type 2 diabetic
      subjects, stimulation of R(d) (second clamp step) in response to both insulin and
      IGF-I was reduced by approximately 40-50% compared with control subjects. In
      control subjects, insulin was more effective than IGF-I in suppressing endogenous
      glucose production (EGP) during both clamp steps. In type 2 diabetic subjects,
      insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF
      I was similar to that of controls. In both control and diabetic subjects, IGF-I
      mediated suppression of plasma FFA concentration and inhibition of FFA turnover
      were markedly impaired compared with insulin (P < 0.01-0.001). During the second
      IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was
      impaired in diabetic vs. control subjects (P < 0.05-0.01). CONCLUSIONS: 1) IGF-I
      is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin
      resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal
      muscle. However, suppression of EGP by IGF-I is not impaired in diabetic
      individuals, indicating normal hepatic sensitivity to IGF-I.

PMID- 12006368
TI  - Effects of recurrent hyperinsulinemia with and without hypoglycemia on
      counterregulation in diabetic rats.
AB  - To understand the mechanisms whereby recurrent hypoglycemia increases the risk of
      subsequent hypoglycemia, it was necessary to differentiate the effects of
      recurrent hyperinsulinemia from those of hyperinsulinemic hypoglycemia. We
      examined basal and hypoglycemic endocrine function in normal rats, streptozotocin
      diabetic controls, and diabetic rats exposed to 4 days of 2 episodes/day of
      hyperinsulinemic hypoglycemia (DH) or hyperinsulinemic hyperglycemia (DI). DH and
      DI rats differentiated the effects of hyperinsulinemia from those of
      hypoglycemia. In diabetic controls, basal plasma ACTH tended to be increased, and
      plasma corticosterone, plasma somatostatin, and pancreatic prosomatostatin and
      proglucagon mRNA were increased (P < 0.05) vs. normal rats. These parameters were
      normalized in DH and DI rats. In diabetic controls, glucagon, epinephrine,
      norepinephrine, corticosterone, and peak glucose production responses to
      hypoglycemia were reduced (P < 0.05) vs. normal rats. In DI rats, epinephrine
      responses were normalized. Conversely, DH rats displayed marked further
      impairment of epinephrine and glucose production responses and increased
      peripheral insulin sensitivity (P < 0.05 vs. diabetic controls). Both insulin
      regimens partially normalized glucagon and fully normalized norepinephrine and
      corticosterone responses. In summary, recurrent hyperinsulinemia in diabetic rats
      normalized most pituitary-adrenal, sympathoadrenal, and pancreatic parameters.
      However, concurrent hypoglycemia further impaired epinephrine and glucose
      production responses and increased insulin sensitivity. We conclude that 1)
      recurrent hypoglycemia may increase the risk of subsequent hypoglycemia by
      increasing insulin sensitivity, and 2) epinephrine counterregulation is
      particularly sensitive to impairment by recurrent hypoglycemia.

PMID- 12006369
TI  - Calcitonin gene expression induced by lipopolysaccharide in the rat pituitary.
AB  - Procalcitonin (PCT), the precursor protein of calcitonin (CT), has been
      considered recently as a significant indicator of bacterial infection and sepsis.
      However, the major source of PCT in sepsis remains unclear. The hypothalamic
      pituitary-adrenal axis is activated during sepsis. Moreover, immunoreactive CT
      (iCT) can be detected in the pituitary. Therefore, we examined the effects of
      lipopolysaccharide (LPS) administration on CT mRNA expression in the pituitary.
      After administration of LPS, CT mRNA expression in the pituitary was increased
      significantly. The increase of CT mRNA was associated with significant elevations
      of the iCT levels in the serum. These results imply that the pituitary is one of
      the sources of the serum PCT during sepsis.

PMID- 12006370
TI  - Role of PDK1 in insulin-signaling pathway for glucose metabolism in 3T3-L1
      adipocytes.
AB  - To investigate the role of 3-phosphoinositide-dependent protein kinase 1 (PDK1)
      in the insulin-signaling pathway for glucose metabolism, wild-type (wt), the
      kinase-dead (kd), or the plecstrin homology (PH) domain deletion (DeltaPH) mutant
      of PDK1 was expressed using an adenovirus gene transduction system in 3T3-L1
      adipocytes. wt-PDK1 and kd-PDK1 were found in both membrane and cytosol
      fractions, whereas DeltaPH-PDK1, which exhibited PDK1 activity similar to that of
      wt-PDK1, was detected exclusively in the cytosol fraction. Insulin dose
      dependently activated protein kinase B (PKB) but did not change atypical protein
      kinase C (aPKC) activity in control cells. aPKC activity was not affected by
      expression of wt-, kd-, or DeltaPH-PDK1 in either the presence or the absence of
      insulin. Overexpression of wt-PDK1 enhanced insulin-induced activation of PKB as
      well as insulin-induced phosphorylation of glycogen synthase kinase
      (GSK)3alpha/beta, a direct downstream target of PKB, although insulin-induced
      glycogen synthesis was not significantly enhanced by wt-PDK1 expression. Neither
      DeltaPH-PDK1 nor kd-PDK1 expression affected PKB activity, GSK3 phosphorylation,
      or glycogen synthesis. Thus membrane localization of PDK1 via its PH domain is
      essential for insulin signaling through the PDK1-PKB-GSK3alpha/beta pathway.
      Glucose transport activity was unaffected by expression of wt-PDK1, kd-PDK1, or
      DeltaPH-PDK1 in either the presence or the absence of insulin. These findings
      suggest the presence of a signaling pathway for insulin-stimulated glucose
      transport in which PDK1 to PKB or aPKC is not involved.

PMID- 12006371
TI  - Selection of odorants for memory tests on the basis of familiarity, perceived
      complexity, pleasantness, similarity and identification.
AB  - In a procedure for the selection of two equivalent sets of familiar and two
      equivalent sets of unfamiliar odours for use in odour memory studies, 24 naive
      subjects were first asked to rate the familiarity, perceived complexity and
      pleasantness of 54 a priori unfamiliar odours and 57 a priori familiar odours and
      to identify the latter. After selection of the 40 most familiar and the 40 least
      familiar odours, the subjects sorted each of these two sets into groups of
      similar odours. Their results were analysed by multidimensional scaling and
      cluster analysis and each set was divided into two recognition sets that had the
      same degree of similarity between target and distractor odours and that had
      similar values of familiarity, pleasantness, perceived complexity (familiar and
      unfamiliar sets) and identifiability (familiar sets). Finally, recognition tasks
      were performed in order to check the equivalence in memory performance of both
      the two familiar and the two unfamiliar recognition sets.

PMID- 12006372
TI  - Novel odorant-binding proteins expressed in the taste tissue of the fly.
AB  - A taste tissue cDNA library of the fleshfly Boettcherisca peregrina was screened
      with a subtracted cDNA probe enriched with taste-receptor-tissue-specific cDNA.
      Seven genes were identified with sequence similarity to insect odorant-binding
      protein (OBP) genes. The predicted amino acid sequences of the genes contain the
      putative signal peptide sequence at the N-terminal and most of them conserve the
      six cysteines common to known insect OBPs. These genes show a high degree of
      sequence divergence with approximately 20% amino acid identity. The most striking
      feature was that all seven of these genes are expressed mainly in the taste
      tissues, such as the labellum and tarsus, unlike the known insect OBP genes
      expressed in olfactory tissue. The predicted amino acid sequences had the highest
      degree of sequence similarity to the Drosophila melanogaster OBPs named pheromone
      binding protein-related proteins (PBPRPs). These gene products are here referred
      to as gustatory PBP-related proteins (GPBPRPs) 1-7. Homologous GPBPRP genes were
      found also in D. melanogaster by database search and are shown to be expressed in
      Drosophila taste tissues.

PMID- 12006373
TI  - Dietary NaCl influences the organization of chorda tympani neurons projecting to
      the nucleus of the solitary tract in rats.
AB  - Prior research has shown that maintained exposure to either a low or high NaCl
      diet from conception to adulthood is associated with changes in NaCl solution
      intake and neural responses of the chorda tympani (CT) nerve. The present study
      examined the influence of maintained exposure to a low or high NaCl diet on the
      central organization of CT neurons projecting to the nucleus of the solitary
      tract (NST). Three groups of rats were reared and maintained on regular chow
      containing either basal 0.1%, intermediate 1.0% or high 6% NaCl from conception
      to adulthood. The fluorescent marker Dil was applied to the CT for
      characterization of afferent terminations and efferent cell body labeling in the
      brainstem. The total NST area occupied by CT afferent fibers was the same for all
      three dietary groups. However, the pattern of CT innervation differed such that
      there was an enlarged dorsal terminal field in the high group. There were no
      group differences in body and brain weight, or in efferent labeled neurons. Thus,
      Dil has been demonstrated to be an effective transport marker of the gustatory
      system and the parameters of dietary NaCl exposure that influence the pattern of
      the CT fibers projecting to the NST have been further clarified.

PMID- 12006374
TI  - Odor discrimination using insect electroantennogram responses from an insect
      antennal array.
AB  - Insects have a highly developed olfactory sensory system, mainly based in their
      antennae, for the detection and discrimination of volatile compounds in the
      environment. Electroantennogram (EAG) response profiles of five different insect
      species, Drosophila melanogaster, Heliothis virescens, Helicoverpa zea, Ostrinia
      nubilalis and Microplitis croceipes, showed different, species-specific EAG
      response spectra to 20 volatile compounds tested. The EAG response profiles were
      then reconstructed for each compound across the five insect species. Most of the
      compounds could be distinguished by comparing the response spectra. We then used
      a four-antenna array, called a Quadro-probe EAG, to see if we could discriminate
      among odorants based on the relative EAG amplitudes evoked when the probe was
      placed in plumes in a wind tunnel and in a field. Stable EAG responses could be
      simultaneously and independently recorded with four different insect antennae
      mounted on the Quadro-probe, and different volatile compounds could be
      distinguished in real time by comparing relative EAG responses with a combination
      of differently tuned insect antennae. Regardless of insect species or EAG
      amplitudes, antennae on the Quadro-probe maintained their responsiveness with
      higher than 1 peak/s of time resolution.

PMID- 12006375
TI  - Taste suppression following lingual capsaicin pre-treatment in humans.
AB  - The effect of oral capsaicin on taste sensations in humans was reinvestigated
      with attention to methodological issues raised in previous studies, including the
      mode of presentation and temperature of the tastant stimulus, as well as the
      sensitizing and desensitizing properties of capsaicin. One-half of the dorsal
      anterior tongue was pre-treated with capsaicin, followed by bilateral tastant
      application (sucrose, NaCl, quinine, monosodium glutamate and citric acid).
      Subjects indicated on which side the taste intensity was greater in a two
      alternative, forced-choice procedure and also rated taste intensity independently
      on each side of the tongue. Each of the five tastants was tested sequentially,
      with reapplication of capsaicin between trials in order to maintain a constant
      level of burn. Four experiments were conducted: (i) a high concentration (33
      p.p.m.) (109 microM) capsaicin effect on taste intensity elicited by high tastant
      concentrations; (ii) a high concentration capsaicin effect on taste intensity
      elicited by low tastant concentrations; (iii) a low concentration (1.5 p.p.m.)
      (4.9 microM) capsaicin effect on taste intensity elicited by low tastant
      concentrations; and (iv) validation of the method for localizing taste by pre
      treating one side of the tongue with Gymnema sylvestre, followed by bilateral
      application of sucrose. In the first experiment, a significant proportion of the
      subjects chose the non-treated side in the two-alternative, forced-choice
      procedure and assigned significantly higher ratings to that side for sucrose
      induced sweetness, quinine-induced bitterness and glutamate-induced umami
      sensations. Salty and sour sensations were not different between sides. A 15 min
      break was imposed in order to allow the capsaicin burn to disappear and
      desensitization to set in, followed by reapplication of the tastant test
      solutions. There were no bilateral differences in the intensity of the sensations
      elicited by any of the five tastants. Similar results were obtained in
      experiments 2 and 3. In the fourth experiment, all 15 subjects tested chose the
      side not treated with Gymnema sylvestre as having a stronger sweet taste and
      assigned significantly higher ratings to that side, thereby validating the method
      for taste localization. These results indicate that oral capsaicin reduces
      certain but not all taste sensations and are discussed in terms of possible
      physiological and cognitive interactions.

PMID- 12006376
TI  - Slow potentials in taste cells induced by frog glossopharyngeal nerve
      stimulation.
AB  - Intracellular recordings were made from the taste cells of atropinized bullfrogs
      while the glossopharyngeal (GP) nerve fibres were electrically stimulated. Two
      types of slow potential, slow hyperpolarizing potentials (HPs) and slow
      depolarizing potentials (DPs), were induced in the taste cells. The slow HPs
      appeared when the lingual capillary blood flow was kept above 0.7 mm/s, whereas
      the slow DPs appeared when the blood flow was slowed down below 0.7 mm/s. The
      membrane resistance of a taste cell increased during the generation of a slow HP,
      but decreased during the generation of a slow DP. The reversal potentials for the
      slow HPs and the slow DPs were recorded at the same membrane potential (-11 to
      approximately -13 mV). Activation of non-selective cation channels possibly
      induced the slow DP and inactivation of those channels possibly induced the slow
      HP in the taste cell membrane. Electrical stimulation of the GP nerve activated a
      population of C fibres in the nerve and possibly released neurotransmitters from
      the nerve terminals. Released neurotransmitters might cause modulation of the
      membrane conductance in taste cells that leads to generation of the slow
      potentials. The present data suggest that slow HPs and slow DPs evoked in the
      taste cells of atropinized frogs by GP nerve stimulation are induced by putative
      neurotransmitters in the taste disc.

PMID- 12006377
TI  - Discrimination between the tastes of sucrose and monosodium glutamate in rats.
AB  - Conditioned taste aversion studies have demonstrated that rats conditioned to
      avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of
      the sodium component of MSG taste, will generalize an aversion for MSG to sucrose
      and vice versa. This suggests that taste transduction for sodium, sucrose and MSG
      may intersect at some point. Generalization of conditioned taste aversion
      indicates that two substances share similar taste features, but it does not
      reveal the extent of their differences. In this study, we tested how well rats
      can discriminate sucrose and MSG under a variety of conditions. Water-deprived
      rats were trained on a combination of water reinforcement and shock avoidance to
      discriminate between MSG and sucrose, both with and without amiloride, and with
      and without equimolar NaCl in all solutions. In the absence of amiloride, rats
      reliably distinguished between MSG and sucrose down to 10 mM solutions. However,
      they could correctly identify solutions only above 50 mM in the presence of
      amiloride, equimolar sodium chloride, or both. These results suggest that
      gustatory stimulation by MSG and sucrose interact somewhere in taste
      transduction, perhaps within taste receptor cells or gustatory afferent pathways.

PMID- 12006378
TI  - Hypoosmotic stimuli activate a chloride conductance in rat taste cells.
AB  - The oral cavity is subjected to a wide range of osmotic conditions, yet little is
      known about how solution osmolarity affects performance of the gustatory system.
      In order to elucidate the mechanism by which hypoosmotic stimuli affect the
      peripheral taste system, I have attempted to characterize the effects of
      hypoosmotic stimuli on individual rat taste receptor cells (TRCs) using whole
      cell patch clamp recording. Currents elicited in response to voltage ramps (-90
      to +60 mV) were recorded in control saline and in solutions varying only in
      osmolarity (-30, -60 and -90 mOsm). In roughly two-thirds of cells, hypoosmotic
      solutions (230 mOsm) caused a 15% increase in cell capacitance and activated a
      reversible conductance that exhibited marked adaptation in the continued presence
      of the stimulus. Similar responses could be elicited in taste cells from taste
      buds in the foliate and vallate papillae, the soft palate, the nasopharynx and
      the epiglottis. Ion substitution experiments were consistent with the
      interpretation that the predominant ion carried through these apparent volume- or
      stretch-activated channels was Cl(-) under normal conditions. Reversal potentials
      for the hypoosmotic-induced current closely matched those predicted by the
      Goldman-Hodgkin-Katz constant field equation for a Cl(-) conductance. The
      relative permeability sequence of the hypoosmotic-activated current in TRCs was
      thiocyanate(-) > or = l(-) > or = Br(-) > Cl(-) > or = F(-) > or = isethionate(-)
      > gluconate(-). Pharmacological experiments revealed that this Cl(-) conductance
      was inhibited by 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid and 5-nitro
      3-(3-phenyl-propylamino)benzoic acid (EC(50) = 1.3 and 4.6 microM, respectively),
      but not by CdCl(2) (300 microM) nor GdCl(3) (200 microM). I hypothesize that this
      hypoosmotic-activated Cl(-) conductance, which is similar to the well
      characterized swelling-activated Cl(-) current, may contribute to volume
      regulation and could represent the transduction mechanism by which the presence
      of hypoosmotic stimuli, including water, may be signaled in taste receptor cells.

PMID- 12006379
TI  - The alarm reaction in crucian carp is mediated by olfactory neurons with long
      dendrites.
AB  - In the present study, we applied a lipophilic tracer, Dil (1,1-dilinoleyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate), to the synaptic region of the
      medial olfactory bulb in formaldehyde-fixed preparations from the crucian carp.
      We observed staining both in the axons of secondary neurons leading to the brain
      and in the olfactory receptor neurons (ORNs) of the olfactory epithelium. In
      those preparations, where staining of the tract was restricted to axons of the
      medial part of the medial olfactory tract, the majority (86-98%) of the somata of
      the sensory neurons were found in the deep layers of olfactory epithelium. Since
      the medial bundle of the medial olfactory tract mediates alarm behaviour in the
      crucian carp, we conclude that the sensory neurons with long dendrites
      participate in the reception of alarm pheromones.

PMID- 12006380
TI  - Breaking the plaque: evidence for plaque rupture in animal models of
      atherosclerosis.

PMID- 12006381
TI  - PTEN-uating restenosis.

PMID- 12006382
TI  - Pleiotropic actions of peroxisome proliferator-activated receptors in lipid
      metabolism and atherosclerosis.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors
      activated by fatty acids and derivatives. Although PPARalpha mediates the
      hypolipidemic action of fibrates, PPARgamma is the receptor for the antidiabetic
      glitazones. PPARalpha is highly expressed in tissues such as liver, muscle,
      kidney, and heart, where it stimulates the beta-oxidative degradation of fatty
      acids. PPARgamma is predominantly expressed in adipose tissues, where it promotes
      adipocyte differentiation and lipid storage. PPARbeta/delta is expressed in a
      wide range of tissues, and recent findings indicate a role for this receptor in
      the control of adipogenesis. Pharmacological and gene-targeting studies have
      demonstrated a physiological role for PPARs in lipid and lipoprotein metabolism.
      PPARalpha controls plasma lipid transport by acting on triglyceride and fatty
      acid metabolism and by modulating bile acid synthesis and catabolism in the
      liver. All 3 PPARs regulate macrophage cholesterol homeostasis. By enhancing
      cholesterol efflux, they stimulate the critical steps of the reverse cholesterol
      transport pathway. As such, PPARs control plasma levels of cholesterol and
      triglycerides, which constitute major risk factors for coronary heart disease.
      Furthermore, PPARalpha and PPARgamma regulate the expression of key proteins
      involved in all stages of atherogenesis, such as monocyte and lymphocyte
      recruitment to the arterial wall, foam cell formation, vascular inflammation, and
      thrombosis. Thus, by regulating gene transcription, PPARs modulate the onset and
      evolution of metabolic disorders predisposing to atherosclerosis and exert direct
      antiatherogenic actions at the level of the vascular wall.

PMID- 12006383
TI  - Sol Sherry lecture in thrombosis: molecular events in acute inflammation.
AB  - The inflammatory response is characterized by a multistep molecular interaction
      between "signaling" cells, such as endothelial cells, and "responding" cells,
      such as neutrophils and monocytes. In the first step, selectins produced by
      signaling cells mediate the tethering of responding cells at sites of
      inflammation. Subsequently, an additional mediator expressed by signaling cells
      activates the tethered responding cells. Under pathological conditions, the same
      mechanism is invoked in inappropriate ways: (1) by prolonged presentation of
      selectins on the cell surface and (2) by the unregulated production of oxidized
      phospholipids that mimic the normal secondary signaling molecule, platelet
      activating factor (PAF). The enzyme PAF acetylhydrolase (PAF-AH) inactivates PAF
      and oxidized phospholipids and constitutes an "off" switch that suppresses
      inflammation. Inhibition of normal PAF-AH function or inactivating mutations of
      the PAF-AH gene can lead to increased susceptibility to inflammatory disease.
      These studies have relevance to atherosclerosis and thrombosis, because
      inflammation is a central feature of both.

PMID- 12006384
TI  - Oxysterols: friends, foes, or just fellow passengers?
AB  - Oxysterols are oxygenated derivatives of cholesterol that are intermediates or
      even end products in cholesterol excretion pathways. Because of their ability to
      pass cell membranes and the blood-brain barrier at a faster rate than cholesterol
      itself, they are also important as transport forms of cholesterol. In addition,
      oxysterols have been ascribed a number of important roles in connection with
      cholesterol turnover, atherosclerosis, apoptosis, necrosis, inflammation,
      immunosuppression, and the development of gallstones. According to current
      concepts, oxysterols are physiological mediators in connection with a number of
      cholesterol-induced metabolic effects. However, most of the evidence for this is
      still indirect, and there is a discrepancy between the documented potent effects
      of oxysterols under in vitro conditions and the studies demonstrating that they
      are of physiological importance in vivo. Oxysterol-binding proteins, such as
      liver X receptor-alpha (a nuclear receptor), do have a regulatory role in
      cholesterol turnover, but the physiological ligand of the protein has not yet
      been defined with certainty. Recently developed genetically engineered mouse
      models with markedly reduced or increased concentration of some of the oxysterols
      have exhibited surprisingly small changes in cholesterol turnover and
      homeostasis. The present review is a critical evaluation of the literature on
      oxysterols, in particular, the in vivo evidence for a role of oxysterols as
      physiological regulators of cholesterol homeostasis and as atherogenic factors.

PMID- 12006385
TI  - Inhibition of vascular smooth muscle cell proliferation, migration, and survival
      by the tumor suppressor protein PTEN.
AB  - Phosphatidylinositol (PI) 3-kinase signaling regulates numerous cellular
      processes, including proliferation, migration, and survival, which are required
      for neointimal hyperplasia and restenosis. The effectors of PI 3-kinase are
      activated by the phospholipid products of PI 3-kinase. In this report, we
      investigated the hypothesis that overexpression of the tumor suppressor protein
      PTEN, an inositol phosphatase specific for the products of PI 3-kinase, would
      inhibit the vascular smooth muscle cell (VSMC) responses necessary for neointimal
      hyperplasia and restenosis. Effects of PTEN were assessed in primary rabbit VSMCs
      after overexpression with a recombinant adenovirus and compared with uninfected
      or control virus-infected cells. PTEN was expressed endogenously in VSMCs, and
      PTEN overexpression inhibited PDGF-induced phosphorylation of p70(s6k), Akt, and
      glycogen synthase kinase-3-alpha and -beta but not ERK1 or -2. Overexpression of
      PTEN significantly inhibited both basal and PDGF-mediated VSMC proliferation and
      migration, the latter possibly due in part to downregulation of focal adhesion
      kinase. Moreover, PTEN overexpression induced cleavage of caspase-3 and
      significantly increased apoptosis compared with control cells. Taken together,
      these results demonstrate that PTEN overexpression potently inhibits the VSMC
      responses required for neointimal hyperplasia and restenosis. Adenovirus
      expressed PTEN may therefore provide a useful tool for the local treatment of
      these and other vascular proliferative disorders.

PMID- 12006386
TI  - Lysophosphatidylcholine activates extracellular signal-regulated kinases 1/2
      through reactive oxygen species in rat vascular smooth muscle cells.
AB  - Lysophosphatidylcholine (lysoPC) acts on vascular smooth muscle cells (VSMCs) to
      produce a mitogenic response through the activation of extracellular signal
      regulated kinases 1/2 (ERK1/2). In the present study, we examined the importance
      of reactive oxygen species (ROS) in lysoPC-stimulated ERK1/2 activation in
      cultured rat VSMCs. Treatment with lysoPC for 3 minutes caused a 2-fold increase
      in intracellular ROS that was blocked by the NADH/NADPH oxidase inhibitor,
      diphenylene iodonium (DPI). Antioxidants, N-acetyl-L-cysteine, glutathione
      monoester, or alpha -tocopherol, inhibited ERK1/2 activation by lysoPC. Almost
      identical results were obtained in the VSMC line A10. Pretreatment of VSMCs with
      DPI but not allopurinol or potassium cyanide (KCN) abrogated the activation of
      ERK1/2. The Flag-tagged p47phox expressed in A10 cells was translocated from the
      cytosol to the membrane after 2 minutes of stimulation with lysoPC. The
      overexpression of dominant-negative p47phox in A10 cells suppressed lysoPC
      induced ERK activation. The ROS-dependent ERK activation by lysoPC seems to
      involve protein kinase C- and Ras-dependent raf-1 activation. Induction of c-fos
      expression and enhanced AP-1 binding activity by lysoPC were also inhibited by
      DPI and NAC. Taken together, these data suggest that ROS generated by NADH/NADPH
      oxidase contribute to lysoPC-induced activation of ERK1/2 and subsequent growth
      promotion in VSMCs.

PMID- 12006387
TI  - Role of isoprenylcysteine carboxyl methyltransferase in tumor necrosis factor
      alpha stimulation of expression of vascular cell adhesion molecule-1 in
      endothelial cells.
AB  - We have previously shown that cytokine stimulation of the expression of vascular
      cell adhesion molecule-1 (VCAM-1), but not that of intercellular adhesion
      molecule-1 (ICAM-1), is redox sensitive in endothelial cells. Here, we
      investigated the role of isoprenylcysteine carboxyl methyltransferase (ICMTase),
      which methylates isoprenylated CAAX (where C indicates cysteine; A, aliphatic
      amino acids; and X, almost any other amino acid) proteins, including Rac1, a
      component of superoxide-generating NAD(P)H oxidase, in the expression of VCAM-1.
      Pretreatment of endothelial cells with N-acetyl-S-farnesyl-L-cysteine (AFC) or N
      acetyl-S-geranylgeranyl-L-cysteine (AGGC), specific inhibitors of ICMTase,
      inhibited the tumor necrosis factor-alpha (TNF-alpha) stimulation of mRNA
      expression of VCAM-1 but not that of ICAM-1. Endothelial cells expressed
      constitutively active ICMTase, as suggested by the presence of methylated Rac1
      and the methylation of AFC by the cells. TNF-alpha stimulation of the cells
      significantly increased the methylation of AFC and Rac1 in endothelial cells.
      That ICMTase was a component of the redox-sensitive signaling pathway was also
      suggested by the AFC inhibition of the generation of reactive oxygen species by
      TNF-alpha. Interestingly, the dominant-negative isoform of Rac1 was not selective
      but inhibited the TNF-alpha stimulation of the mRNA expression of VCAM-1 and ICAM
      1. Thus, ICMTase is a critical component of the redox-sensitive VCAM-1-selective
      signaling pathway, and it appears to activate a discrete inflammatory signaling
      pathway, at least in part, through the methylation of Rac1.

PMID- 12006388
TI  - Role of nuclear factor-kappa B activation in metalloproteinase-1, -3, and -9
      secretion by human macrophages in vitro and rabbit foam cells produced in vivo.
AB  - Metalloproteinase secretion by macrophages is believed to play a key role in the
      matrix degradation that underlies atherosclerotic plaque instability and aneurysm
      formation. We studied the hypothesis that nuclear factor-kappaB (NF-kappaB), a
      transcription factor, is necessary for metalloproteinase secretion and, hence, is
      a target for pharmacological intervention. Adenovirus-mediated gene transfer of
      the inhibitory NF-kappaB subunit, I-kappa Balpha, was achieved into human
      monocyte-derived macrophages in vitro and into foam cells produced in vivo in
      cholesterol-fed rabbits. Human macrophages and rabbit foam cells secreted matrix
      degrading metalloproteinase (MMP)-9 without further stimulation, and this was not
      inhibited by I-kappaBalpha (11+/-16% and 8+/-10%, respectively; P> 0.05). MMP-1
      secretion from human macrophages increased in response to recombinant human CD40
      ligand and was inhibited 92+/-5% by I-kappaBalpha (n=3, P<0.05). Rabbit foam
      cells secreted MMP-1 and -3 without further stimulation, and this was inhibited
      83+/-12% and 69+/-11%, respectively, by I-kappaBalpha (n=6 or 7, P<0.001). I
      kappaBalpha did not significantly affect the expression or activity of tissue
      inhibitor of metalloproteinases-1 or -2. Overexpression of I-kappaBalpha
      inhibited collagenolytic and beta-caseinolytic activity by 42+/-2% and 41+/-7%,
      respectively (n=3, P<0.05). Secretion of MMP-1 and MMP-3 from macrophages
      stimulated in vitro or in vivo depends on the activation of NF-kappaB. Because
      the inhibition of NF-kappaB reduces proteolytic activity, it appears to be an
      attractive pharmacological target in unstable atheromas.

PMID- 12006389
TI  - Hyperhomocysteinemia evoked by folate depletion: effects on coronary and carotid
      arterial function.
AB  - High circulating concentrations of homocysteine (ie, hyperhomocysteinemia [Hhcy])
      impair the vascular function of peripheral conduit arteries and arterioles
      perfusing splanchnic and skeletal muscle regions. The effects of HHcy on coronary
      resistance vessel function and other indexes of vascular function, ie, arterial
      permeability and stiffening, are unclear. We tested the hypotheses that HHcy
      impairs coronary resistance vessel reactivity; increases carotid arterial
      permeability; and initiates arterial stiffening. Male rats that consumed folate
      replete (CON, n=44) or folate-deplete (HHcy, n=48) chow for 4 to 5 weeks had
      total plasma homocysteine concentrations of 7+/-2 or 58+/-4 micromol/L,
      respectively. Maximal acetylcholine-evoked relaxation (approximately 40% vs
      approximately 60%) and tension development from baseline in response to nitric
      oxide synthase inhibition (approximately 20% vs approximately 40%) were lower
      (both P<0.05) in coronary resistance vessels (approximately 120 microm, internal
      diameter) isolated from HHcy versus CON animals, respectively, whereas sodium
      nitroprusside-evoked relaxation and contractile responses to serotonin and
      potassium chloride were similar between groups. Permeability to 4400 MW and 65
      000 MW fluorescently labeled (TRITC) dextran reference macromolecules
      (quantitative fluorescence microscopy) was approximately 44% and approximately
      24% greater (P<0.05), respectively, in carotid arteries from HHcy versus CON
      rats. Maximal strain, evaluated by using a vessel elastigraph, was less (
      approximately 32% vs 42%, P<0.05) in carotid arterial segments from HHcy versus
      CON animals, respectively. Finally, estimates of oxidative (copper-zinc+manganese
      superoxide dismutase activity) and glycoxidative (pentosidine) stress were
      elevated (P<0.05) in arterial tissue from HHcy versus CON rats. These findings
      suggest that moderately severe HHcy evoked by folate-depletion impairs
      endothelium-dependent relaxation of coronary resistance vessels, increases
      carotid arterial permeability, and initiates arterial stiffening. HHcy may
      produce these effects by a mechanism associated with increased oxidative and
      glycoxidative stress.

PMID- 12006390
TI  - Long pentraxin PTX3 upregulates tissue factor expression in human endothelial
      cells: a novel link between vascular inflammation and clotting activation.
AB  - Inflammation is a major contributing factor to atherosclerotic plaque development
      and ischemic heart disease. PTX3 is a long pentraxin that was recently found to
      be increased in patients with acute myocardial infarction. Because tissue factor
      (TF), the in vivo trigger of blood coagulation, plays a dominant role in thrombus
      formation after plaque rupture, we tested the possibility that PTX3 could
      modulate TF expression. Human umbilical vein endothelial cells, incubated with
      endotoxin (lipopolysaccharide) or the inflammatory cytokines interleukin-1beta
      and tumor necrosis factor-alpha, expressed TF. The presence of PTX3 increased TF
      activity and antigen severalfold in a dose-dependent fashion. PTX3 exerted its
      effect at the transcription level, inasmuch as the increased levels of TF mRNA,
      mediated by the stimuli, were enhanced in its presence. The increase in mRNA
      determined by PTX3 originated from an enhanced nuclear binding activity of the
      transacting factor c-Rel/p65, which was mediated by the agonists and measured by
      electrophoretic mobility shift assay. The mechanism underlying the increased c
      Rel/p65 activity resided in an enhanced degradation of the c-Rel/p65 inhibitory
      protein IkappaBalpha. In the area of vascular injury, during the inflammatory
      response, cell-mediated fibrin deposition takes place. Our results suggest that
      PTX3, by increasing TF expression, potentially plays a role in thrombogenesis and
      ischemic vascular disease.

PMID- 12006391
TI  - Characteristics of intact and ruptured atherosclerotic plaques in brachiocephalic
      arteries of apolipoprotein E knockout mice.
AB  - The brachiocephalic arteries of fat-fed apolipoprotein E knockout mice develop
      plaques that frequently rupture and form luminal thromboses. The morphological
      characteristics of plaques without evidence of instability or with healed
      previous ruptures (intact) and vessels with acutely ruptured plaques (ruptured)
      have now been defined, to understand the process of plaque destabilization in
      more detail. Ninety-eight apolipoprotein E knockout mice were fed a diet
      supplemented with 21% lard and 0.15% cholesterol, for 5 to 59 weeks. Of these 98
      mice, 51 had an acutely ruptured plaque in the brachiocephalic artery. Ruptured
      and intact plaques differed in terms of plaque cross-sectional area (intact,
      0.109+/-0.016 mm2; ruptured, 0.192+/-0.009 mm2; P=0.0005), luminal occlusion
      (intact, 35.3+/-3.3%; ruptured, 57.7+/-1.9%; P<0.0001), the number of buried caps
      within the lesion (intact, 1.06+/-0.12; ruptured, 2.66+/-0.16; P<0.0001), fibrous
      cap thickness (intact, 4.7+/-0.6 microm; ruptured, 2.0+/-0.3 microm; P=0.0004),
      and lipid fractional volume (intact, 35.9+/-3.0%; ruptured, 50.7+/-2.2%;
      P=0.0019). This study confirms that plaque rupture is a frequent occurrence in
      the brachiocephalic arteries of apolipoprotein E knockout mice on a high-fat
      diet. The data also show that ruptured plaques in these mice show many of the
      characteristics of vulnerable plaques in humans. This supports the use of this
      model in studies of the mechanisms and therapy of plaque rupture.

PMID- 12006392
TI  - Enhanced atherogenesis is not an obligatory response to systemic herpesvirus
      infection in the apoE-deficient mouse: comparison of murine gamma-herpesvirus-68
      and herpes simplex virus-1.
AB  - Viral and bacterial infectious agents have been implicated in the etiology of
      atherosclerosis. We have previously shown that a gamma-herpesvirus can accelerate
      atherosclerosis in the apolipoprotein E-deficient (apoE-/-) mouse. To address
      whether a virally induced systemic immune response is sufficient to trigger
      enhanced atheroma formation, we infected apoE-/- mice with murine gamma
      herpesvirus-68 (MHV-68) or herpes simplex virus-1 (HSV-1). In this study, we show
      that both viruses were able to induce a cell-mediated and humoral immune response
      in the apoE-/- mouse, which was sustained over a period of 24 weeks. Although
      intranasal or intraperitoneal infection with MHV-68 induced similar levels of
      virus-specific IgG1 and IgG2a antibodies in the serum of apoE-/- mice, those
      infected with HSV-1 showed higher anti-HSV-1 IgG2a compared with IgG1 antibody
      levels. In addition, viral message was not detected in the aortas of HSV-1
      infected animals, whereas we have shown previously that MHV-68 mRNA can be
      detected in the aortas of infected mice as early as 5 days after infection.
      Compared with control mice, apoE-/- mice infected with MHV-68 showed accelerated
      atherosclerosis, whereas mice infected with HSV-1 did not. These data indicate
      that a systemic immune response to any particular infectious agent is
      insufficient to induce enhanced atherosclerosis in the apoE-/- mouse and point to
      specific infections or immune mechanisms that might be essential for virally
      enhanced atherogenesis.

PMID- 12006393
TI  - Intensive lipid lowering by statin therapy does not improve vasoreactivity in
      patients with type 2 diabetes.
AB  - Cardiovascular disease is the most important cause of morbidity and mortality in
      patients with type 2 diabetes. Endothelial dysfunction predicts cardiovascular
      outcome. Type 2 diabetes is characterized by endothelial dysfunction, which may
      be caused by dyslipidemia. Statin therapy restores endothelial function in
      hyperlipidemic patients. Therefore, we hypothesize a beneficial effect of
      atorvastatin on NO-dependent vasodilation in patients with type 2 diabetes and
      mild dyslipidemia (low density lipoproteins >4.0 mmol/L and/or triglycerides >1.8
      mmol/L). We evaluated the effect of intensive lipid lowering (4 weeks of 80 mg
      atorvastatin once daily) on vasoreactivity in 23 patients with type 2 diabetes by
      using venous occlusion plethysmography. Twenty-one control subjects were matched
      for age, sex, body mass index, blood pressure, and smoking habits. The ratio of
      blood flows in the infused (measurement [M]) and noninfused (control [C]) arm was
      calculated for each recording (M/C ratio), and M/C% indicates the percentage
      change from the baseline M/C ratio. Serotonin-induced NO-dependent vasodilation
      was significantly blunted (52+/-30 versus 102+/-66 M/C%, P<0.005), and
      nitroprusside-induced endothelium-independent vasodilation was modestly reduced
      (275+/-146 versus 391+/-203 M/C%, P<0.05) in patients with type 2 diabetes
      compared with control subjects. Despite significant reduction of total
      cholesterol, low density lipoproteins, and triglycerides (5.8+/-1.0 to 3.2+/-0.6
      [P<0.0001], 4.1+/-1.1 to 1.8+/-0.7 [P<0.0001], and 2.2+/-1.3 to 1.4+/-0.5
      [P<0.05] mmol/L, respectively), no effect on NO-dependent (59+/-44 M/C%) and
      endothelium-independent (292+/-202 M/C%) vasodilation was demonstrated. These
      data suggest that intensive lipid lowering by atorvastatin has no effect on NO
      availability in forearm resistance arteries in type 2 diabetic patients. Other
      factors, such as hyperglycemia, may be a more important contributing factor
      regarding impaired vasoreactivity in this patient group.

PMID- 12006394
TI  - Association between the PPARA L162V polymorphism and plasma lipid levels: the
      Framingham Offspring Study.
AB  - Peroxisome proliferator activated receptor (PPAR) alpha is a member of the
      nuclear receptor superfamily that regulates key proteins involved in fatty acid
      oxidation, extracellular lipid metabolism, hemostasis, and inflammation. A L162V
      polymorphism at the PPARA locus has been associated with alterations in lipid and
      apolipoprotein concentrations. We studied the association among lipids,
      lipoproteins, and apolipoproteins and the presence of the L162V polymorphism in
      2373 participants (1128 men and 1244 women) in the Framingham Offspring Study.
      The frequency of the less common allele (V162) was 0.069. The V162 allele was
      associated with increased serum concentrations of total and LDL cholesterol in
      men (P=0.0012 and P=0.0004, respectively) and apolipoprotein B in men (P=0.009)
      and women (P=0.03 after adjustment for age, body mass index, smoking, and use of
      beta-blockers, diuretics or estrogens). Apolipoprotein (apo) C-III concentrations
      were higher in carriers of the V162 allele. The association of the L162V
      polymorphism on LDL cholesterol concentration was greatest in those who also
      carried the E2 allele at the APOE locus and the G allele at the APOC3 3238C>G
      polymorphism. This suggests that alterations in triglyceride-rich lipoprotein
      metabolism may be involved in the generation of the increase in LDL cholesterol
      observed with the L162V PPARA polymorphism.

PMID- 12006395
TI  - Delayed and exaggerated postprandial complement component 3 response in familial
      combined hyperlipidemia.
AB  - Very low density lipoprotein overproduction is the major metabolic characteristic
      in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty
      acids (FFAs) in vitro may be impaired in FCHL by decreased action of acylation
      stimulating protein (ASP), which is identical to the immunologically inactive
      complement component 3a (C3adesArg). Because decreased FFA uptake by impaired
      complement component 3 (C3) response (as the precursor for ASP) may result in
      enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes
      in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched
      control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP
      levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L,
      respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L,
      respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations
      increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3
      was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients
      occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48
      concentration was reached after 6 hours in FCHL patients and control subjects.
      Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation)
      were significantly higher in FCHL patients than in control subjects, and the
      early postprandial C3 rise was negatively correlated with the postprandial FFA
      and hydroxybutyric acid concentrations. The present data suggest an impaired
      postprandial plasma C3 response in FCHL patients, most likely as a result of a
      delayed response by C3, as the precursor for the biologically active ASP, acting
      on FFA metabolism. Therefore, an impaired postprandial C3 response may be
      associated with impaired peripheral postprandial FFA uptake and, consequently,
      lead to increased hepatic FFA flux and very low density lipoprotein
      overproduction.

PMID- 12006396
TI  - Association of estrogen receptor-alpha gene polymorphisms with coronary artery
      disease in patients with familial hypercholesterolemia.
AB  - To investigate the association of estrogen receptor (ER)-alpha gene polymorphisms
      with coronary artery disease (CAD), we studied 197 men and 98 postmenopausal
      women with heterozygous familial hypercholesterolemia. We examined the known
      polymorphisms, including PvuII, XbaI, TA repeat, and CA repeat, and identified 6
      novel polymorphisms in the ER-alpha gene. The distributions of -1989T/G (a novel
      polymorphism in promoter B) and XbaI in intron 1 were associated with CAD in
      postmenopausal women and in men, with a higher frequency of the G/G genotype
      (P=0.03) or X1/X1 genotype (P=0.02) in the CAD group. The frequency of alleles of
      TA repeats >17 was found to be significantly higher in postmenopausal women with
      CAD than in those without CAD (P=0.04), but not in men. Logistic regression
      analysis with all coronary risk factors as covariates showed that the G/G
      genotype was a higher risk for CAD (odds ratio 4.5, 95% CI 1.0 to 19.5;P=0.04)
      but that X1/X1 was not. We conclude that -1989T/G or its linked polymorphisms in
      the ER-alpha gene may confer risk for CAD and that the G/G genotype may be an
      independent predictor for CAD in patients with familial hypercholesterolemia.

PMID- 12006397
TI  - Impact of alcohol intake on measures of lipid metabolism depends on context
      defined by gender, body mass index, cigarette smoking, and apolipoprotein E
      genotype.
AB  - Hyperlipidemia, smoking, and obesity are well-known risk factors for
      cardiovascular disease. Conversely, moderate alcohol intake is associated with
      lower atherosclerosis risk. However, the influence of taking alcohol on the
      interrelationships of these factors in a particular context has not been
      thoroughly investigated. In this study, we asked whether the association between
      plasma measures of lipid metabolism and alcohol intake is dependent on context
      defined by gender, age, body mass index (BMI), smoking, and apolipoprotein E
      (APOE) genotype. Data were obtained in a sample of 869 women and 824 men who
      participated in the Quebec Heart Health Survey. There was no evidence that
      variation among APOE genotypes influenced the association between LDL cholesterol
      (LDL-C) or HDL cholesterol (HDL)-C and alcohol, after adjustment for age and BMI.
      Further, the positive (LDL-C and BMI) and the negative (HDL-C and BMI)
      associations that were observed in men and women with the epsilon3/2 and
      epsilon3/3 genotypes were not modified by alcohol intake. However, in women with
      the epsilon4/3 genotype only, we found a significant influence of an alcohol by
      BMI interaction on the prediction of total cholesterol, LDL-C, HDL-C, apoA-I, and
      apoB, and this interaction was influenced by the status of smoking. Whereas the
      influence of an alcohol by BMI interaction on total cholesterol and LDL-C was
      significant in smokers, its influence on HDL-C was significant only in non
      smokers. This study emphasizes the context dependency of the influence of alcohol
      on lipid metabolism and demonstrates how biological, environmental, and genetic
      factors interact to determine cardiovascular disease risk.

PMID- 12006398
TI  - Population-based twin study of the effects of migration from Finland to Sweden on
      endothelial function and intima-media thickness.
AB  - Finnish men have higher coronary heart disease (CHD) mortality than Swedish men
      do. To assess the impact of migration to a country with lower CHD mortality on
      subclinical atherosclerosis, we measured early functional and structural
      atherosclerotic vascular changes in twins discordant for migration from Finland
      to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the
      brachial artery, carotid intima-media thickness, and carotid artery compliance
      were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69
      years, in which co-one twin had migrated more than 20 years ago permanently to
      Sweden. There were no significant differences in CHD risk factors except for
      diastolic blood pressure and body fat percentage, which were higher in Sweden. In
      all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs
      4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly
      significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant
      difference in intima-media thickness or carotid artery compliance between Sweden
      and Finland. We conclude that in Finnish monozygous twins the endothelial
      function is better among the twins that have migrated to a country with lower CHD
      prevalence.

PMID- 12006399
TI  - Inflammatory mediators and cell adhesion molecules as indicators of severity of
      atherosclerosis: the Rotterdam Study.
AB  - Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular
      events. It is not clear whether they reflect the severity of underlying
      atherosclerotic disease. Within the Rotterdam Study, we investigated the
      associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble
      intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1
      with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a
      random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion
      molecules were assessed in a subsample of 714 participants. In multivariate
      analyses, logarithmically transformed CRP (regression coefficient [beta]=-0.023,
      95% CI -0.033 to -0.012) and IL-6 (beta=-0.025, 95% CI -0.049 to -0.001) were
      inversely associated with the ankle-arm index. Only CRP was associated with
      carotid intima-media thickness (beta=0.018, 95% CI 0.010 to 0.027). Compared with
      the lowest tertile, the odds ratio for moderate to severe carotid plaques
      associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0).
      Soluble intercellular adhesion molecule-1 levels were strongly associated with
      carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest
      tertile]). Soluble vascular cell adhesion molecule-1 was not significantly
      associated with any of the measures of atherosclerosis. This study indicates that
      CRP is associated with the severity of atherosclerosis measured at various sites.
      Associations of the other markers with atherosclerosis were less consistent.

PMID- 12006400
TI  - Heritability of subclinical atherosclerosis in Latino families ascertained
      through a hypertensive parent.
AB  - Although clinical coronary heart disease and many cardiovascular risk factors are
      well known to aggregate within families, the heritability of carotid artery
      intima-media thickness (IMT) is less well documented. We report IMT heritability
      estimates in Mexican American, Salvadoran American, or Guatemalan American (all
      referred to as Latino) families ascertained through a hypertensive proband. IMT
      and cardiovascular risk factors (age, sex, blood pressure, body mass index,
      lipids, fasting glucose, and insulin sensitivity) were measured in 204 adult
      offspring of 69 hypertensive probands, along with 82 parents (54 probands and 28
      spouses). In the offspring, variance component analysis revealed a heritability
      for IMT of 64% (P< 0.0001) after adjustment for significant cardiovascular risk
      factors. Genetic factors accounted for 50% of the total variation in IMT, whereas
      significant cardiovascular risk factors explained 22% (14% were due to age). For
      offspring and parents combined, adjusted IMT heritability was less, 34%
      (P=0.0005), with genetic factors accounting for 18% of the total IMT variation,
      whereas significant cardiovascular risk factors explained 46% (38% were due to
      age). We conclude that variation in common carotid artery IMT is heritable in
      Latino families with a hypertensive proband. Heritability is particularly evident
      in younger family members, suggesting that acquired factors contribute
      progressively to IMT variability with aging.

PMID- 12006401
TI  - Age and sex distribution of subclinical aortic atherosclerosis: a magnetic
      resonance imaging examination of the Framingham Heart Study.
AB  - Autopsy data demonstrate a correlation between subclinical aortic atherosclerosis
      and cardiovascular disease. Therefore, noninvasive cardiovascular magnetic
      resonance (CMR) of subclinical atherosclerosis may provide a novel measure of
      cardiovascular risk, but it has not been applied to an asymptomatic population
      based cohort to establish age- and sex-specific normative data. Participants in
      the Framingham Heart Study offspring cohort who were free of clinically apparent
      coronary disease were randomly sampled from strata of sex, quartiles of age, and
      quintiles of Framingham Coronary Risk Score. Subjects (n=318, aged 60+/-9 years,
      range 36 to 78 years, 51% women) underwent ECG-gated T2-weighted black-blood
      thoracoabdominal aortic CMR scanning. CMR evidence of aortic atherosclerosis was
      noted in 38% of the women and 41% of the men. Plaque prevalence and all measures
      of plaque burden increased with age group and were greater in the abdomen than in
      the thorax for both sexes and across all age groups. In addition, the Framingham
      Coronary Risk Score was significantly correlated with all plaque prevalence and
      burden measures for women but only for men after age adjustment. These
      noninvasive CMR data extend the prior autopsy-based prevalence estimates of
      subclinical atherosclerosis and may help to lay the foundation for future studies
      of risk stratification and treatment of affected individuals.

PMID- 12006402
TI  - Induction of plasminogen activator inhibitor-1 in endothelial cells by basic
      fibroblast growth factor and its modulation by fibric acid.
AB  - Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis and proteolysis.
      Basic fibroblast growth factor (bFGF) stimulates angiogenesis, which requires
      regional proteolysis. Because modulation of vasculopathy requires tight control
      of proteolysis, effects of bFGF on PAI-1 expression in endothelial cells (ECs)
      were characterized. bFGF increased PAI-1 mRNA and accumulation of PAI-1 protein
      in conditioned media in human umbilical vein ECs. The bFGF-mediated increase in
      PAI-1 mRNA was attenuated by inhibition of extracellular signal-regulated kinase
      kinase in human ECV304 cells. The rate of decrease in PAI-1 mRNA after
      actinomycin D treatment was not affected by bFGF. Transient transfection assays
      of the human PAI-1 promoter-luciferase construct demonstrated that bFGF-induced
      PAI-1 transcription was dependent on the elements within the -313 to -260 bp
      relative to the transcription start site. This region contains an E26
      transformation specific 1 (Ets-1)-like site. Electrophoretic mobility shift assay
      showed that bFGF increased nuclear translocation or DNA binding of the Ets-1-like
      transcription factor to the PAI-1 promoter. Nucleotide substitution to disrupt
      the Ets-1-like site reduced bFGF-stimulated promoter activity. Fenofibric acid,
      an agonist ligand for the peroxisome proliferator-activated receptor-alpha,
      inhibited basal and bFGF-stimulated PAI-1 expression. By inducing PAI-1
      expression from ECs, bFGF may control proteolysis and fibrinolysis in vessel
      walls.

PMID- 12006403
TI  - PAR-4 agonist AYPGKF stimulates thromboxane production by human platelets.
AB  - Previous reports have indicated that thrombin-induced thromboxane production by
      human platelets occurs through two types of interaction between thrombin and the
      platelet surface. One of these interactions is with protease activated
      receptor(PAR)-1, the first identified thrombin receptor. These studies were
      undertaken to determine whether stimulation of PAR-4 also results in thromboxane
      production. The results show that treatment of washed human platelets with the
      PAR-4 agonist AYPGKF stimulates a maximum of 40% to 60% of the thromboxane
      produced by 100 nmol/L thrombin. Maximal thromboxane production requires
      approximately 1.0 mmol/L AYPGKF, despite the observation that maximal aggregation
      is produced by 45 micromol/L AYPGKF. Thromboxane produced by the combined
      stimulation of PAR-1 and PAR-4 is additive. Pretreatment of platelets with 45
      micromol/L AYPGKF partially desensitizes thromboxane production in response to
      higher concentrations of AYPGKF and thrombin but not to stimulation by SFLLRN.
      PAR-4-induced stimulation is also significantly inhibited by 60 micromol/L
      genistein. It is concluded that activation through either PAR-1 or PAR-4 results
      in thromboxane production, but that stimulation of neither receptor alone
      produces thromboxane equivalent to that produced by 100 nmol/L thrombin. Thus,
      these findings demonstrate the presence of two pathways for thrombin-induced
      thromboxane production by platelets as proposed previously.

PMID- 12006404
TI  - Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and
      genotype in relation to myocardial infarction in the north and south of Europe.
AB  - The thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described
      inhibitor of fibrinolysis that decreases plasminogen binding to the fibrin
      surface. The plasma TAFI concentration is almost entirely genetically determined.
      We investigated whether plasma TAFI levels and polymorphisms located in the TAFI
      gene could constitute risk markers of myocardial infarction (MI). Plasma TAFI
      antigen (Ag) levels were assayed by ELISA and 2 TAFI gene polymorphisms
      (Ala147Thr and C+1542G in the 3' untranslated region) were determined in a large
      European case-control study. This study compared 598 men recruited 3 to 6 months
      after MI with 653 age-matched controls from North Europe (Stockholm, Sweden, and
      London, England) and South Europe (Marseilles, France, and San Giovanni Rotondo,
      Italy). A TAFI Ag value above the 90th percentile was associated with a
      significantly lower risk of MI (odds ratio 0.55, P<0.02), indicating that
      elevated TAFI may be protective against MI. As previously shown, the 2 TAFI gene
      polymorphisms were in strong linkage disequilibrium and were associated with the
      TAFI Ag concentration, with carriers of the Thr147 and 1542C alleles having
      higher levels (P<0.0005). These effects were similar in controls and cases and in
      each center. There was a difference in allele frequency between cases and
      controls for the Ala147Thr polymorphism, with Thr147 allele carriers being more
      frequent in controls than in cases in 2 centers, Stockholm (P=0.03) and San
      Giovanni Rotondo (P=0.03); the odds ratio for the entire cohort was 0.78
      (P<0.05). In conclusion, patients with a recent MI presented lower values of TAFI
      Ag and higher frequencies of the "TAFI-decreasing" alleles. The geographical
      differences observed do not contribute to explaining the North-South gradient in
      MI risk in Europe.

PMID- 12006406
TI  - Genome-wide linkage analysis of the acute coronary syndrome suggests a locus on
      chromosome 2.
AB  - A positive family history is a recognized cardiovascular risk factor, and genome
      wide scans may reveal susceptibility loci for coronary artery disease. The acute
      coronary syndrome, consisting of myocardial infarction and unstable angina, is
      the most important manifestation of coronary disease and is characterized by
      atherosclerotic plaque disruption and coronary thrombosis. From approximately
      6000 hospital admissions to cardiology units, we identified affected sibling
      pairs (n=61) who had documented acute coronary syndrome before the age of 70
      years. A 10-cM resolution genetic map and MAPMAKER/SIBS were used for genome-wide
      linkage analysis. One locus on chromosome 2q36-q37.3 showed linkage with a lod
      score of 2.63 (P<0.0001). Separate multipoint fine-mapping of this locus with
      independent markers replicated the linkage results (lod 2.64). Two other regions
      on chromosomes 3q26-q27 and 20q11-q13 showed lod scores in excess of 1.5
      (P<0.005). This genome scan in acute coronary syndrome suggests 1 locus that
      encompasses the gene encoding the insulin receptor substrate-1 gene. Two other
      potential loci were identified. These data imply that a limited number of potent
      susceptibility genes exist for the acute coronary syndrome. Such genes are likely
      to be relevant to the combined processes of atherosclerosis, plaque instability,
      and coronary thrombosis.

PMID- 12006409
TI  - Haplotype-specific effects on endothelial NO synthase promoter efficiency:
      modifiable by cigarette smoking.
AB  - The T-786C promoter and 27-bp repeat intron 4 polymorphisms in the endothelial NO
      synthase (eNOS) gene have been inconsistently associated with various eNOS
      related phenotypic changes. We explored molecular mechanisms underlying the
      inconsistency. We constructed pGL3 luciferase reporter vectors by inserting an
      eNOS promoter fragment containing either T or C nucleotide at -786 bp at the 5'
      end of the luciferase coding region and eNOS intron 4 containing either 5x or
      4x27-bp repeats at the 3' end of the luciferase gene. The transcription
      efficiency in the T promoter was lower than in the C promoter (15.7+/-1.0% vs
      83.3+/-5.8%, P<0.01 when 5x27-bp was an enhancer and 37.6+/-4.7% vs 58.9+/-7.5%,
      P<0.01 when 4x27bp was an enhancer). Although cigarette smoking extracts
      treatment increased the transcription efficiency significantly in the T promoter
      (1.7-fold, P<0.01), it reduced the C promoter efficiency (by 10% to 15%). A
      mobility shift assay revealed positive binding of the 27-bp repeat fragment with
      endothelial cell nuclear protein extracts. Our study demonstrates a cis-acting
      role of the 27-bp repeats in eNOS promoter function and a haplotype-specific
      expression pattern determined by DNA variants at -786 bp and intron 4 of the eNOS
      gene that is also modifiable by cigarette smoking.

PMID- 12006410
TI  - Interferon-gamma-mediated downregulation of cholesterol efflux and ABC1
      expression is by the Stat1 pathway.
AB  - The pathological role of interferon-gamma (IFN-gamma) in atherosclerosis is
      mediated through effects on macrophages, foam cells, and other vascular cells.
      Recently, we reported that ATP-binding cassette transporter 1(ABC1) message and
      protein levels were decreased 3- to 4-fold in foam cells by IFN-gamma. In the
      present study, the pathway by which IFN-gamma inhibited ABC1 expression was
      investigated with signal transducers and activators of transcription (Stat1)
      knockout mice. IFN-gamma-stimulated, wild-type, macrophage-derived foam cells, as
      previously reported, exhibited a decrease in cholesterol efflux and ABC1
      expression as well as an increase in acyl coenzyme A:cholesterol-O
      acyltransferase activity. However, IFN-gamma treatment of foam cells from Stat1
      knockout mice failed to demonstrate reductions in efflux or ABC1 expression at
      the message or protein levels, nor were there any increases in acyl coenzyme
      A:cholesterol-O-acyltransferase activity. However, ABC1 mRNA expression in
      macrophages from Stat1 knockout mice could still be demonstrated to be increased
      by lipid loading with acetylated low density lipoprotein. Finally, Stat1
      independent gene activation by IFN-gamma was intact in the Stat1 KO macrophages,
      inasmuch as IFN-gamma was shown to stimulate increases in interleukin-6
      production in the Stat1 KO macrophages that were comparable to those observed in
      the wild-type macrophages. Therefore, Stat1 signaling is necessary and sufficient
      for the inhibitory effects of IFN-gamma on cholesterol efflux and ABC1
      expression.

PMID- 12006411
TI  - Production of the long pentraxin PTX3 in advanced atherosclerotic plaques.
AB  - Elevated plasma levels of the pentraxin protein family member C-reactive protein
      (CRP) are associated with increased risk of cardiovascular disease in both
      healthy and high-risk subjects. The long pentraxin family member, pentraxin 3
      (PTX3), was recently described. Like CRP, PTX3 is induced by acute inflammatory
      stimuli and is increased in the blood of patients with acute myocardial
      infarction. Unlike CRP, it is expressed in a wide range of cell types, but not in
      hepatocytes. In this study, we have investigated the expression of PTX3 in
      atherosclerosis. Immunohistochemical staining of advanced atherosclerotic lesions
      revealed strong expression of PTX3. In contrast, no PTX3 expression was observed
      in nonatherosclerotic internal mammary arteries. By staining serial sections with
      cell type- and PTX3-specific antibodies, we observed that PTX3 was produced
      principally by macrophages and endothelial cells. Infrequent expression by smooth
      muscle cells was also observed. Our results suggest that PTX3 may contribute to
      the pathogenesis of atherosclerosis.

PMID- 12006412
TI  - Pneumonology or pneumology?: An etymologic approach.

PMID- 12006413
TI  - Acupuncture for asthma: fact or fiction?

PMID- 12006414
TI  - Lung cancer screening: who will pick up the tab?

PMID- 12006415
TI  - Ventilator-associated pneumonia and surgical patients.

PMID- 12006416
TI  - Cytokines, genes, and ARDS.

PMID- 12006417
TI  - Pulmonary Munchausen syndrome.

PMID- 12006418
TI  - Near-fatal asthma: what have we learned?

PMID- 12006419
TI  - Short-term acupuncture therapy is of no benefit in patients with moderate
      persistent asthma.
AB  - STUDY OBJECTIVES: Acupuncture traditionally has been used to treat asthma.
      Nevertheless, only a few controlled studies have been performed to determine the
      efficacy of this treatment. Our study aimed to determine the efficacy of
      acupuncture in patients with moderate persistent asthma. METHODS: Twenty-three
      patients with moderate persistent asthma who had been treated only with inhaled
      beta(2)-agonists were randomly assigned to receive four sessions of real
      acupuncture (RA) or sham acupuncture (SA) in a blinded manner. After a washout
      period of 3 weeks, the patients were crossed over. Monitoring included FEV(1),
      methacholine challenge, daily peak flow (PF) variability, and the keeping of an
      asthma diary. RESULTS: Twenty of 23 patients completed the study. There was no
      significant change in FEV(1) following treatment. The mean (+/- SE) FEV(1) values
      before and after the RA were 73 +/- 4% and 73 +/- 3%, respectively (not
      significant [NS]). FEV(1) values before and after SA were 70 +/- 3% and 70 +/-
      3%, respectively (NS). There was also no change in provocative methacholine
      concentration causing a 20% fall in FEV(1) (PC(20)) before and after treatment.
      The mean PC(20) values before and after RA were 0.92 +/- 0.42 mg/mL and 1.16 +/-
      0.51 mg/mL, respectively (p = 0.71), while the PC(20) values before and after SA
      were 1.47 +/- 0.83 mg/mL and 1.11 +/- 0.79 mg/mL, respectively (p = 0.59). There
      was no change in the mean PF variability before and after the RA (1.6 +/- 3.1%
      and 1.8 +/- 2.3%, respectively [NS]). The PF variability before and after SA were
      3.6 +/- 2.8% and 2.8 +/- 3.4%, respectively (NS). No significant difference was
      demonstrated for symptom scores or for the use of beta(2)-agonist inhalers (RA,
      6.7 +/- 3.4; SA, 8.1 +/- 3.6; p = 0.58). CONCLUSION: In patients with moderate
      persistent asthma, a short course of acupuncture treatment resulted in no change
      in lung functions, bronchial hyperreactivity, or patient symptoms.

PMID- 12006420
TI  - Comparison of the effects of salmeterol and formoterol in patients with severe
      asthma.
AB  - STUDY OBJECTIVE: Several studies have demonstrated the superiority of salmeterol
      and formoterol to either regular treatment with albuterol or placebo. However, to
      date there have been no trials comparing the efficacy of salmeterol and
      formoterol in patients with severe asthma. DESIGN: We undertook a randomized,
      placebo-controlled, crossover study to compare 4 weeks of treatment with inhaled
      formoterol (12 microg twice daily) or salmeterol (50 microg twice daily) in
      patients with severe asthma whose conditions were not being adequately controlled
      by therapy with high doses of inhaled corticosteroids (i.e., > or = 1,500 microg
      daily) or with regular oral corticosteroid treatment. Morning pretreatment peak
      expiratory flow (PEF) during the last 14 days of the treatment period was the
      primary outcome variable. Patients recorded morning and evening pretreatment PEF,
      daytime and nighttime symptom scores, and any use of rescue medication.
      Spirometry and bronchial reversibility were performed after each treatment.
      RESULTS: Forty-two nonsmoking patients (29 women; mean age, 45 +/- 2 years; mean
      [+/- SEM] FEV(1), 61.8 +/- 3.4% of predicted) took part in the trial, and 27
      patients completed the trial. The mean morning PEF was greater in patients
      receiving formoterol (mean increase, 14.4 L/min; 95% confidence interval [CI].
      0.2 to 28.6) or salmeterol (mean increase, 14.8 L/min; 95% CI, 0.5 to 29.1)
      compared with those receiving placebo, but there was no difference between these
      treatments. There were no significant treatment effects for any of the secondary
      outcome variables (i.e., FEV(1,) FVC, mean evening PEF, mean daytime symptom
      score, or nighttime symptom score). CONCLUSION: We conclude that the long-acting
      beta(2)-agonists salmeterol and formoterol improve morning PEF in patients with
      severe asthma, but that there is no difference in efficacy between the two drugs.

PMID- 12006421
TI  - Near-fatal asthma: a population-based study of risk factors.
AB  - BACKGROUND: The study of near-fatal asthma (NFA) may provide a means to further
      our understanding of fatal asthma. Studies of NFA often are derived from a single
      ICU rather than from a defined population. We therefore aimed to identify factors
      distinguishing NFA patients (cases) from those persons treated in an emergency
      department (ED) [ED control subjects] and in the community (community control
      subjects [CCs]). METHODS: This was a population-based case-control study
      conducted over 20 months of 45 NFA patients (age range, 5 to 50 years), 197 ED
      control subjects treated in an ED, and 303 CCs, all of whom were residents of
      Alberta. RESULTS: The age distribution was similar between NFA patients and
      control subjects, with the majority being < 22 years of age (NFA patients, 68.9%;
      ED control subjects, 71.3%; CCs, 60.7%). Those patients with NFA were
      significantly more likely to have received a diagnosis before 5 years of age
      (66.6%), compared to ED control subjects (39.6%) and CCs (28.7%). The NFA group
      was significantly more likely to report moderate-to-severe disease and more
      frequent symptoms than the other groups. Therapy with bronchodilators was used
      most frequently by the NFA group compared to the ED control subjects and CCs (p <
      0.001), as was therapy with inhaled steroids (p < 0.001) and oral steroids (p <
      0.001). NFA patients had higher scores for vulnerability and were most likely to
      admit to stress as an asthma trigger. All groups had high exposure to cigarette
      smoke and pets. CONCLUSION: NFA patients have many modifiable risk factors and
      many similarities to ED control subjects and CCs with asthma. General measures to
      improve asthma control and awareness of risks are required in all groups.

PMID- 12006422
TI  - Alterations in airway inflammation and lung function during corticosteroid
      therapy for atopic asthma.
AB  - INTRODUCTION: Although corticosteroid therapy for asthma improves lung function
      and reduces airway inflammation, the relation between these two events is
      unclear. This article investigates associations between changes in bronchial
      inflammation and lung function during high-dose inhaled corticosteroid therapy
      for asthma. METHODS: Nine subjects with atopic asthma received high-dose inhaled
      fluticasone propionate (FP), 2,000 microg/d for 8 weeks. Fiberoptic bronchoscopy
      with endobronchial biopsies, spirometry, and histamine provocation challenge were
      performed on each subject at baseline, after 2 weeks, and again after 8 weeks of
      therapy. Spearman rank correlation coefficients between changes in parameters of
      bronchial inflammation and lung function were computed. RESULTS: As expected,
      significant down-regulation of airway inflammation and improvements in lung
      function were observed after both short-term and long-term therapy with high-dose
      inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage
      numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+
      eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of
      therapy. Although changes in airway inflammation and changes in lung function
      were not closely associated after 2 weeks of therapy, changes in eosinophils
      (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator
      response (r = 0.77, p = 0.016) after 8 weeks of therapy. CONCLUSION: In patients
      with atopic asthma, changes in bronchial eosinophils and lung function during
      steroid therapy are closely related but do not occur simultaneously.

PMID- 12006423
TI  - Reduced interleukin-18 levels in BAL specimens from patients with asthma compared
      to patients with sarcoidosis and healthy control subjects.
AB  - STUDY OBJECTIVES: To investigate whether differing airway interleukin (IL)-18
      levels may be implicated in the pathogenesis of asthma and sarcoidosis. SETTING:
      University teaching hospital. PATIENTS AND METHODS: IL-18 levels were measured in
      BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar
      macrophages obtained by BAL from 15 patients with sarcoidosis, 11 patients with
      asthma, and 13 healthy subjects. We also examined the relationship between IL-18
      levels and macrophage and lymphocyte concentrations in BAL fluid. IL-18 was
      measured using an in-house enzyme-linked immunosorbent assay. RESULTS: IL-18
      levels were significantly lower in BAL fluid from patients with asthma (median,
      0.0 pg/mL; interquartile range, 0.0 to 0.0 pg/mL) compared to patients with
      sarcoidosis (median, 222.0 pg/10(6); interquartile range, 110 to 340 pg/mL; p =
      0.009, Mann Whitney rank-sum test) and healthy control subjects (median, 162
      pg/mL; interquartile range, 38 to 203 pg/mL; p = 0.025, Mann Whitney rank-sum
      test). Individual analyses comparing IL-18 levels with BAL macrophage counts, and
      IL-18 with lymphocyte counts in the three groups showed no correlation between
      these indexes. The mean levels of IL-18 in unstimulated macrophage supernatants
      were 410 pg/10(6) cells for patients with asthma, 723.4 pg/10(6) cells for
      patients with sarcoidosis, and 734.8 pg/10(6) cells for healthy control subjects
      (p > 0.05). Stimulated macrophages from patients with sarcoidosis responded with
      increasing amounts of IL-18 at lower doses of LPS than macrophages from healthy
      control subjects or patients with asthma. CONCLUSION: Our findings suggest that
      inherently low levels of IL-18 may be associated with the pathogenesis of
      asthmatic airway inflammation.

PMID- 12006424
TI  - Cough and phlegm are important predictors of health status in smokers without
      COPD.
AB  - STUDY OBJECTIVES: The health-related quality of life of smokers without COPD and
      that of ex-smokers has not been defined. If abnormal, the role of small airways
      disease and that of cough and phlegm have never been evaluated. Therefore, the
      aim of the study was to explore whether the differences in quality of life
      between smokers and ex-smokers could be explained by cough and phlegm,
      differences in pulmonary function tests, or exercise capacity. DESIGN:
      Observational, prospective. SETTING: Pulmonary and Critical Care Division, COPD
      Center at St. Elizabeth's Medical Center. POPULATION: In 36 smokers, 21 ex
      smokers (stopped smoking for > 20 years), 19 never-smokers with normal FVC and
      FEV(1) values, and 41 patients with COPD (FEV(1) 38 +/- 11% predicted [mean +/-
      SD]), the St. George's Respiratory Questionnaire (SGRQ), pulmonary function
      tests, and a 6-min walk distance (6MWD) were performed. RESULTS: The total SGRQ
      scores were worse in current smokers (15 +/- 15) than in ex-smokers (6 +/- 4) or
      never-smokers (4 +/- 3) [p < 0.05]. As expected, the worst score was seen in COPD
      (50 +/- 15). After correcting for cough and phlegm, the difference in SGRQ scores
      between smokers and ex-smokers disappeared. In current and ex-smokers, the SGRQ
      score was associated with the exposure to pack-years smoking history (r = 0.45, p
      < 0.01, and r = 0.83, p < 0.0001, respectively) but independent of lung function
      or exercise parameters (6MWD). CONCLUSIONS: In smokers without COPD, the abnormal
      SGRQ score is due to the noxious effect of cigarette smoke, resulting in cough
      and phlegm, independent of its physiologic effects.

PMID- 12006425
TI  - Dyspnea is a better predictor of 5-year survival than airway obstruction in
      patients with COPD.
AB  - BACKGROUND: FEV(1) is regarded as the most significant correlate of survival in
      COPD and is used as a measure of disease severity in the staging of COPD.
      Recently, however, the categorization of patients with COPD on the basis of the
      level of dyspnea has similarly been reported to be useful in the prediction of
      health-related quality of life and improvement in exercise performance after
      pulmonary rehabilitation. STUDY OBJECTIVES: We compared the effects of the level
      of dyspnea and disease severity, as evaluated by airway obstruction, on the 5
      year survival rate of patients with COPD. DESIGN AND METHODS: A total of 227
      patients with COPD were enrolled in a 5-year, prospective, multicenter study in
      the Kansai area of Japan, involving 20 divisions of respiratory medicine from
      various university and city hospitals. RESULTS: After 5 years, 183 patients were
      available for the follow-up examination (follow-up rate, 81%). The 5-year
      cumulative survival rate among patients with COPD was 73%. The effect of disease
      staging, based on the American Thoracic Society (ATS) guideline as evaluated by
      the percentage of predicted FEV(1), on the 5-year survival rate was not
      significant (p = 0.08). However, the level of dyspnea was significantly
      correlated to the 5-year survival rate (p < 0.001). The Cox proportional hazards
      model revealed that the level of dyspnea had a more significant effect on
      survival than disease severity based on FEV(1). CONCLUSIONS: The categorization
      of patients with COPD on the basis of the level of dyspnea was more
      discriminating than staging of disease severity using the ATS guideline with
      respect to 5-year survival. Dyspnea should be included as one of the variables,
      in addition to airway obstruction, for evaluating patients with COPD in terms of
      mortality.

PMID- 12006426
TI  - Mortality after hospitalization for COPD.
AB  - OBJECTIVES: To identify variables associated with mortality in patients admitted
      to the hospital for acute exacerbation of COPD. DESIGN: Prospective cohort study.
      SETTING: Acute-care hospital in Barcelona (Spain). PATIENTS: One hundred thirty
      five consecutive patients hospitalized for acute exacerbation of COPD, between
      October 1996 and May 1997. MEASUREMENTS AND RESULTS: Clinical, spirometric, and
      gasometric variables were evaluated at the time of inclusion in the study.
      Socioeconomic characteristics, comorbidity, dyspnea, functional status,
      depression, and quality of life were analyzed. Mortality at 180 days, 1 year, and
      2 years was 13.4%, 22%, and 35.6%, respectively. Sixty-four patients (47.4%) were
      dead at the end of the study (median follow-up duration, 838 days). Greater
      mortality was observed in the bivariate analysis among the oldest patients (p <
      0.0001), women (p < 0.01), and unmarried patients (p < 0.002). Hospital admission
      during the previous year (p < 0.001), functional dependence (Katz index) [p <
      0.0004], greater comorbidity (Charlson index) [p < 0.0006], depression (Yesavage
      Scale) [p < 0.00001]), quality of life (St. George's Respiratory Questionnaire
      [SGRQ]) [p < 0.01], and PCO(2) at discharge (p < 0.03) were also among the
      significant predictors of mortality. In the multivariate analysis, the activity
      SGRQ subscale (p < 0.001; odds ratio [OR], 2.62; confidence interval [CI], 1.43
      to 4.78), comorbidity (p < 0.005; OR, 2.2; CI, 1.26 to 3.84), depression (p <
      0.004; OR, 3.6; CI, 1.5 to 8.65), hospital readmission (p < 0.03; OR, 1.85; CI,
      1.26 to 3.84), and marital status (p < 0.0002; OR, 3.12; CI, 1.73 to 5.63) were
      independent predictors of mortality. CONCLUSIONS: Quality of life, marital
      status, depressive symptoms, comorbidity, and prior hospital admission provide
      relevant information of prognosis in this group of COPD patients.

PMID- 12006427
TI  - Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and
      COPD.
AB  - BACKGROUND: Although exacerbations are the main cause of medical visits and
      hospitalizations of patients with chronic bronchitis and COPD, little information
      is available on the costs of their management. OBJECTIVE: This study attempted to
      determine the total direct costs derived from the management of exacerbations of
      chronic bronchitis and COPD in an ambulatory setting. METHOD: A total of 2,414
      patients with exacerbated chronic bronchitis and COPD were recruited from 268
      general practices located throughout Spain. Patients were followed up for 1
      month. RESULTS: A total of 507 patients (21%) relapsed; of these, 161 patients
      (31.7%) required attention in emergency departments and 84 patients (16.5%) were
      admitted to the hospital. The total direct mean cost of all exacerbations was
      $159; patients who were hospitalized generated 58% of the total cost. Cost per
      failure was $477.50, and failures were responsible for an added mean cost of
      $100.30/exacerbation. Exacerbations of the 1,130 patients with COPD had a mean
      cost of $141. Sensitivity analysis showed that a 50% reduction in the failure
      rate (from 21 to 10.5%) would result in a total cost of exacerbation of $107 (33%
      reduction). CONCLUSION: Exacerbations of chronic bronchitis and COPD are costly,
      but the greatest part of costs derives from therapeutic failures, particularly
      those that end in hospitalization.

PMID- 12006428
TI  - Dual energy X-ray absorptiometry outcomes in male COPD patients after treatment
      with different glucocorticoid regimens.
AB  - STUDY OBJECTIVES: To compare bone mineral density (BMD) outcomes of patients who
      received continuous oral systemic glucocorticoids (GCs) with BMD outcomes of
      patients who received multiple GC courses, oral or IV. DESIGN: Cross-sectional
      study. PARTICIPANTS: Eighty-six white men with COPD selected from the outpatient
      clinic for pulmonary diseases. INTERVENTION: Data analysis from medical records,
      bone densitometry, and pulmonary function tests of consecutive selected patients.
      Inclusion period into the study was exactly 1 year. MEASUREMENTS AND RESULTS: Ten
      patients received oral prednisolone daily (group 1). Eleven patients were treated
      for several exacerbations with multiple systemic prednisolone courses, up to a
      period of 2 weeks per course, with a cumulative dose of > or = 1,000 mg (group
      2). Likewise, 28 patients were treated with multiple systemic prednisolone
      courses, but with a cumulative dose < 1,000 mg (group 3). Thirty-seven patients
      were never treated with systemic prednisolone, and partly with inhaled
      corticosteroids (ICS) [group 4]. All groups were balanced for age and pack-years
      of smoking. In group 2, body mass index (BMI) and FEV(1) were lowest and
      hyperinflation was highest. The cumulative systemic prednisolone dose was highest
      in group 1, irrespective of the additional ICS treatments. Dual energy x-ray
      absorptiometry scanning of the lumbar spine, total hip, and femoral neck regions
      revealed a T score < or = 2.5 SD in 27 patients (31%), 31 patients (36%), and 34
      patients (40%), respectively. BMD outcomes at any site were lower in patients
      receiving multiple systemic prednisolone courses > 1,000 mg, cumulatively (group
      2), compared to the other groups, and these values were (mean +/- 1 SD) 0.759 +/-
      0.238 g/cm(2), 0.683 +/- 0.115 g/cm(2), and 0.686 +/- 0.125 g/cm(2), respectively
      (p < 0.0001). Multivariate regression analysis revealed a correlation between the
      cumulative dose of prednisolone in group 2 and BMD of the lumbar spine (adjusted
      r = 0.48; p < 0.01). At the total hip and femoral neck regions, only a
      correlation between BMI and BMD was observed (adjusted r = 0.65 and 0.58,
      respectively; p < 0.0001 for both sites). CONCLUSIONS: Despite a far lower
      cumulative GC dose in comparison with patients treated with systemic
      corticosteroids continuously, after adjusting for BMI and lung function,
      osteoporosis of the lumbar spine was most frequent in patients receiving > 1,000
      mg of prednisolone cumulatively, administered in multiple courses for the
      treatment of exacerbations of COPD.

PMID- 12006429
TI  - Focal ground-glass opacity detected by low-dose helical CT.
AB  - OBJECTIVE: Focal ground-glass opacity (GGO) has been detected increasingly by low
      dose helical CT. Although focal GGO suggests in situ neoplastic lesion in the
      peripheral lung, it remains controversial how to manage these lesions. The
      purpose of this study was to evaluate the pathologic and radiologic
      characteristics of focal GGO in order to develop a standard of treatment for
      these lesions. PATIENTS: Forty-three patients with persistent focal GGO < or = 2
      cm in size from January 1998 to September 2000 were studied. Thoracoscopic lung
      biopsy was performed consecutively for persistent focal GGO following a several
      month observation period (mean, 3.7 months). RESULTS: The histologic diagnoses
      were bronchioloalveolar carcinoma (BAC) in 23 patients, adenocarcinoma with mixed
      subtypes in 11 patients, and atypical adenomatous hyperplasia (AAH) in 9
      patients. None of 34 carcinoma patients had lymph node involvement. All of 17
      lesions > or = 1 cm in size were malignant. GGO with solid components on high
      resolution CT were highly associated with adenocarcinoma (malignant rate, 93.3%).
      CONCLUSIONS: Persistent focal GGO after observation for several months was a
      finding of early adenocarcinoma or its precursor. Especially, lesions > or = 1 cm
      in size or GGO with solid component were significant signs of malignancy. We
      concluded lung biopsy should be attempted for persistent focal GGO.

PMID- 12006430
TI  - Aortic calcification on plain chest radiography increases risk for coronary
      artery disease.
AB  - STUDY OBJECTIVES: To determine whether an association exists between aortic
      calcification viewed on plain chest radiography and coronary artery disease.
      METHODS: Retrospective review of all chest radiographs obtained from consecutive
      patients undergoing coronary angiography at a primary cardiac center during 1999.
      Plain chest radiographs were reviewed by blinded radiologists, and interobserver
      consistency was measured. The presence or absence of aortic arch calcification
      was abstracted and compared with the results of coronary angiography. RESULTS: Of
      654 cases, 329 of 360 patients with aortic arch calcification vs. 241 of 294
      patients without aortic arch calcification had coronary artery disease
      demonstrated on angiography. The 9% absolute difference in proportions was
      significant (p = 0.0003). The relative risk (measured by risk ratio) was 1.11
      (95% confidence interval, 1.05 to 1.19). CONCLUSION: Several objective signs
      (e.g., hypertension, hyperlipidemia, and ECG changes) have been associated
      previously with the presence of coronary artery disease. This study further
      suggests an association between coronary disease and aortic arch calcification on
      plain chest radiography. These results may assist primary-care providers
      performing routine health assessments as well as emergency practitioners
      evaluating patients with potential angina.

PMID- 12006431
TI  - Significance of abnormal chest radiograph findings in patients with HIV-1
      infection without respiratory symptoms.
AB  - STUDY OBJECTIVES: Patients with HIV-1 infection or AIDS may present with abnormal
      chest radiograph (CXR) findings in the absence of symptoms specific to the lung.
      The objective was to determine the spectrum of disease and the diagnostic
      modalities employed in these patients. METHODS: From 1996 to 1998, we identified
      patients with HIV-1 infection presenting to the Bellevue Hospital Chest Service
      with abnormal CXR findings, and absence of specific pulmonary symptoms. Charts
      were reviewed for presence of constitutional symptoms, CD4 lymphocyte count, use
      of Pneumocystis carinii pneumonia (PCP) prophylaxis, eventual diagnosis, and all
      diagnostic modalities employed. CXR findings were classified according to their
      predominant abnormalities: nodules, infiltrates, cavity, mass, adenopathy, or
      effusion. RESULTS: Forty-four patients were eligible for inclusion. Eight-six
      percent of patients had a CD4 lymphocyte count < 200 cells/microL, and 57% were
      receiving PCP prophylaxis. Nodular disease was the most common radiographic
      abnormality (57%), followed by adenopathy (17%). A definitive diagnosis was
      obtained in 86% of the patients. The most common diagnosis was tuberculosis
      (26%), followed by nontuberculous mycobacteria (NTM; 23%) and Kaposi sarcoma
      (12%). No patients had PCP or bacterial pneumonia. Sixty-two percent of patients
      required an invasive modality to establish a diagnosis. Only 18% of patients with
      tuberculosis (2 of 11 patients) received diagnoses by sputum analysis.
      CONCLUSIONS: Patients with HIV-1 infection, abnormal CXR findings, and lack of
      pulmonary symptoms have a high incidence of infectious disorders, especially
      pulmonary tuberculosis and infection due to NTM. The high prevalence of treatable
      and potentially communicable disorders warrants an aggressive diagnostic approach
      in these patients.

PMID- 12006432
TI  - The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase
      1 in cryptogenic organizing pneumonia.
AB  - BACKGROUND: The processes observed in interstitial lung disease are associated
      with the production, deposition, and proteolysis of the extracellular matrix
      (ECM), which may lead to irreversible pulmonary structural remodeling or to
      appropriate repair without fibrosis. Matrix metalloproteinases (MMPs) and a
      tissue inhibitor of metalloproteinases (TIMPs) are known to regulate remodeling
      of the ECM and thus to be important in the process of lung fibrosis. Pulmonary
      structures are extensively remodeled in usual interstitial pneumonia (UIP),
      whereas severe architectural remodeling is minimally present in cryptogenic
      organizing pneumonia (COP). However, not much is known about the roles of MMP-9
      and/or TIMP-1 in COP. METHODS: Levels of MMP-9, TIMP-1 and the molar ratio of MMP
      9/TIMP-1 in BAL fluids were investigated in 11 patients with UIP, in 8 patients
      with COP, and in 10 control subjects. We checked the levels of MMP-9 and TIMP-1
      by means of enzyme immunoassay, and the hydrolytic activity of MMP-9 in BAL
      fluids was measured by gelatin zymography. Further, we evaluated the expression
      of MMP-9 and TIMP-1 in lung tissue by immunohistochemistry. RESULTS: The
      concentrations of MMP-9 and TIMP-1 were significantly increased in patients with
      UIP and were even higher in patients with COP compared with control subjects. The
      levels of MMP-9 and TIMP-1 were significantly higher in patients with COP than in
      patients with UIP. The molar ratio of MMP-9/TIMP-1 was significantly higher in
      patients with COP than in control subjects. In patients with COP, the
      concentration of MMP-9 significantly correlated with the number of neutrophils
      and lymphocytes. Zymographic analysis revealed that the activity of the 92-kd pro
      MMP-9 was increased in patients with UIP and was even higher in patients with
      COP, compared with control subjects. CONCLUSIONS: These data suggest that
      overproduction of MMP-9 and TIMP-1, and an imbalance between MMP-9 and TIMP-1,
      may have a role as diagnostic references in COP.

PMID- 12006433
TI  - Applying sputum as a diagnostic tool in pneumonia: limited yield, minimal impact
      on treatment decisions.
AB  - STUDY OBJECTIVES: We evaluated the role of sputum examination in the management
      of patients with community-acquired pneumonia (CAP) in a primary-care hospital
      without microbiologic laboratory facilities. DESIGN AND INTERVENTIONS: A
      diagnostic strategy using regular collection of sputum samples, Gram staining in
      a local laboratory, and mailing of samples to a commercial laboratory for culture
      analysis. SETTING: A 200-bed primary-care hospital without subspeciality
      physicians. PATIENTS: One hundred sixteen consecutive patients with a diagnosis
      of CAP were prospectively evaluated during a 12-month period. RESULTS: Of 116
      patients, 42 patients (36%) were capable of producing a sputum sample. Age > or =
      75 years (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.18 to 0.93) and
      prior ambulatory antimicrobial treatment (OR, 3.2; 95% CI, 1.2 to 8.4) were
      independent predictors of sputum production. A delay in collection and processing
      of sputum samples of > 24 h was present in 31% and 39%, respectively. A delay in
      collection yielded an increased number of Gram-negative enteric bacilli and
      nonfermenters (44% vs. 7%, p = 0.056). A delay in processing was associated with
      an increased number of Candida spp isolates (33% vs. 9%, p = 0.16). The overall
      diagnostic yield was low (10 of 116 patients, 9%) due to a limited number of
      valid samples (n = 23 of 42 patients, 55%) and a limited number of definitely or
      probably positive samples on Gram's stain and culture (n = 10 of 42 patients,
      24%). Prior ambulatory antimicrobial treatment was associated with a reduction in
      diagnostic yield (14% vs. 56%, p = 0.09). The impact of diagnostic results on
      antimicrobial treatment decisions was minimal, with antimicrobial treatment
      directed to diagnostic results in only one patient. CONCLUSIONS: We conclude that
      in this setting representative of primary-care hospitals in Germany, sputum had a
      low diagnostic yield and did not contribute significantly to patient management.

PMID- 12006434
TI  - Role of interleukin-18 and T-helper type 1 cytokines in the development of
      Mycoplasma pneumoniae pneumonia in adults.
AB  - STUDY OBJECTIVE: Interleukin (IL)-18 is a proinflammatory cytokine, originally
      termed interferon (IFN)-gamma-inducing factor, which promotes T-helper type 1
      (Th1) cytokine responses. We recently reported that serum IL-18 levels were
      elevated in children with Mycoplasma pneumoniae pneumonia (MP). In this study, we
      investigated the contribution of IL-18 to the infection and assessed the Th1
      cytokine response to pulmonary involvement in adults. METHODS: We investigated
      the clinical course, pulmonary involvement, and serum levels of IL-18, IFN-gamma,
      IL-12p40, and soluble IL-2 receptor (sIL-2R) in 21 patients with acute-stage MP
      and in 21 age- and sex-matched control subjects. RESULTS: Significantly (p <
      0.001) increased serum IL-18 (median, 248 pg/mL [range, 89 to 441 pg/mL] vs.
      median, 126 pg/mL [range, 47 to 217 pg/mL]) and sIL-2R (median, 617 U/mL [range,
      410 to 1,032 U/mL] vs. median, 425 U/mL [range, 268 to 601 U/mL]) were found in
      patients with MP as compared with healthy control subjects, and there was a
      tendency toward increased serum IFN-gamma and IL-12p40. Circulating IL-18 values
      had a positive correlation with serum sIL-2R levels (r = 0.62, p = 0.028) and the
      number of affected pulmonary lobes (sigma = 0.61, p = 0.024), but not with the
      serum levels of antibodies to M pneumoniae, IFN-gamma, or IL-12p40. Serum IL-18
      and sIL-2R values in severe cases were significantly higher (p < 0.03) than those
      in mild cases. IFN-gamma and sIL-2R levels in four patients with pleural effusion
      were significantly (p < 0.05) higher than those in the other 17 subjects.
      CONCLUSIONS: Serum levels of IL-18 were raised during the acute phase of MP. We
      suggest IL-18 and Th1 cytokines may play a significant role in the
      immunopathologic responses in MP.

PMID- 12006435
TI  - Endobronchial ultrasonography for mediastinal and hilar lymph node metastases of
      lung cancer.
AB  - STUDY OBJECTIVES: Conventional radiologic procedures are frequently unreliable in
      the diagnosis of mediastinal and hilar lymph node metastases of lung cancer. In
      order to improve diagnostic accuracy, we performed endobronchial ultrasonography
      (EBUS) during bronchofiberscopic examinations of patients with lung cancer.
      METHODS AND PATIENTS: To evaluate mediastinal and hilar lymph node metastases,
      EBUS was performed prospectively using a radial scanning probe of 20 MHz through
      a bronchofiberscope. RESULTS: We observed hilar lymph nodes (10R, 11R superior,
      11R inferior, 12R, 10L, 11L, 12L) in 20 of 37 patients who underwent EBUS, and we
      could clearly identify whether direct invasion of the pulmonary artery by a lymph
      node had occurred. Of the 27 patients who showed no hilar lymph nodes on chest CT
      scan, lymph node swellings < 10 mm or > or = 10 mm in diameter were identified by
      EBUS in 9 patients and 2 patients, respectively. Interestingly, EBUS also
      revealed that the pulmonary artery was directly invaded by an interlobar lymph
      node < 10 mm in diameter in one patient. In most patients, lymph node 7 was
      easily identified and was clearly differentiated from the surrounding esophagus,
      vessels, and mediastinal fat tissue by EBUS. However, fused lymph nodes or lymph
      nodes with low central density when visualized by chest CT scan were occasionally
      observed as independent lymph nodes by EBUS. When compared with the pathologic
      diagnosis of lymph node metastasis in 16 patients who underwent surgery, the most
      specific and sensitive method for identifying lymph node metastases were EBUS
      alone (92%) and EBUS in combination with CT scan (100%), respectively. The
      overall accuracy of EBUS was 94% for the diagnosis of direct invasion of the
      pulmonary arteries by a hilar lymph node. CONCLUSIONS: EBUS in combination with
      conventional radiologic tools may contribute to improved staging, especially in
      surgical cases with hilar lymph node metastases.

PMID- 12006436
TI  - Screening for lung cancer with CT: a preliminary cost-effectiveness analysis.
AB  - STUDY OBJECTIVE: To appraise the potential cost-effectiveness of lung cancer
      screening with CT. STUDY DESIGN: Incremental cost-effectiveness ratios are
      estimated for two hypothetical cohorts followed up over time. One cohort was
      screened over the first 5 years of the study period; the other cohort received
      usual care. Cost streams are projected for each cohort under alternative sets of
      parameters/ assumptions and from the perspective of national payer groups. Cohort
      cost differentials arise as a result of screening and variations in stage
      specific treatment. Cohort life expectancies are also projected, and they too
      differ as a consequence of variations in the stage distribution at diagnosis. The
      ratios of these cost and life-expectancy differences are used to judge the
      expected economic value of screening. RESULTS: Results are analyzed for a "worst
      case" scenario, ie, with the highest cost and lowest yield assumptions. Under
      these conditions, screening with CT costs approximately $48,000 per life-year
      gained, if screening results in 50% of lung cancers detected at localized stage.
      Smaller proportions of cancer detected at a localized stage result in higher cost
      effectiveness ratios, and vice versa. CONCLUSION: If screening for lung cancer is
      effective, it is likely to be cost-effective if the screening process can detect
      > 50% of cancers at localized stage.

PMID- 12006437
TI  - Staging in lung cancer: is 3 cm a prognostic threshold in pathologic stage I non
      small cell lung cancer? A multicenter study of 1,020 patients.
AB  - INTRODUCTION: Since 1974, a tumor size of 3 cm in diameter has been regarded as
      the prognostic threshold in the staging of bronchogenic carcinoma. OBJECTIVE: To
      study the prognostic behavior of surgical-pathologic tumor size in non-small cell
      lung cancer (NSCLC) with complete resection. DESIGN: Four-year multi
      institutional prospective study from 1993 to 1997. PATIENTS: Consecutive cases of
      NSCLC in pathologic stages IA-IB (pIA-pIB) treated surgically with complete
      resection in hospitals belonging to the Bronchogenic Carcinoma Co-operative Group
      of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). METHODS: The
      Schoenfeld procedure was used to identify different prognostic groups,
      considering 1 cm as the measurement unit. RESULTS: Based on the 1,020 cases
      evaluated, four prognostic groups were identified: 0 to 2 cm (group A; n = 147),
      2.1 to 4 cm (group B; n = 448), 4.1 to 7 cm (group C; n = 336), and > 7 cm (group
      D; n = 89). At 5 years, survival was 0.63 (95% confidence interval [CI], 0.58 to
      0.68), 0.56 (95% CI, 0.53 to 0.59), 0.49 (95% CI, 0.46 to 0.52), and 0.38 (95%
      CI, 0.32 to 0.44) for groups A, B, C, and D, respectively. Differences between
      paired groups (log-rank) were significant: 0.0074 between groups A and B, 0.0048
      between groups B and C, and 0.0034 between groups C and D. CONCLUSIONS: In
      initial stages (pIA-pIB) of NSCLC, the 3-cm value was not found to behave as a
      prognostic threshold; in this study, four surgical-pathologic tumor size groups
      were identified with strong prognostic differences: from 0 to 2 cm, from 2.1 to 4
      cm, from 4.1 to 7 cm, and > 7 cm.

PMID- 12006438
TI  - The incidence and the risk of pneumothorax and chest tube placement after
      percutaneous CT-guided lung biopsy: the angle of the needle trajectory is a novel
      predictor.
AB  - STUDY OBJECTIVE: Pneumothorax remains the most common complication of
      percutaneous CT-guided lung biopsy, despite improved techniques. The rate of
      pneumothorax reported in the literature ranges from 19 to 60%. The aims of this
      study were to estimate the risk of pneumothorax in patients undergoing CT-guided
      lung biopsy, and to determine which factors affect its occurrence. DESIGN:
      Retrospective study. PATIENTS AND METHODS: This study involved 289 consecutive
      patients who underwent biopsy in our hospital under consistent methods, using
      only one type of needle, the 19-gauge Tokyo Medical College (TMC) Needle (Takei;
      Tokyo, Japan), under CT guidance. RESULT: Seventy-seven patients (26.6%) had
      pneumothorax after percutaneous CT-guided lung biopsy. Forty-one of the 77
      patients (53.2%) who had pneumothorax (14.2% of the entire series) required
      placement of a chest tube. Our present study, using multivariate logistic
      regression analysis, confirmed that greater lesion depth, wider trajectory angle,
      and increasing FVC percent predicted are independent risk factors of
      pneumothorax, and that two former factors are independent risk factors of chest
      tube placement following percutaneous CT-guided lung biopsy. CONCLUSIONS: The
      angle of needle route is a novel predictor of this complication. Our findings
      suggest that low pneumothorax rates are achieved by combining several techniques
      to reduce the risk of pneumothorax.

PMID- 12006439
TI  - Are femoral Broviac catheters effective and safe? A prospective comparison of
      femoral and jugular venous broviac catheters in newborn infants.
AB  - STUDY OBJECTIVES: Patients with femoral venous catheters are commonly believed to
      be at higher risk of infectious complications as compared to patients with
      jugular catheters. Although reports have suggested that femoral venous Broviac
      catheters (Davol; Cranston, RI) are safe, no comparisons with jugular catheters
      were presented. Thus, we compared our efficacy and complications of femoral and
      jugular venous Broviac catheters in newborns. METHODS: We prospectively recorded
      demographic data, cannulation requirements, duration of catheter use, and
      complications. SETTING: Special-care nursery. PATIENTS: Newborns. INTERVENTIONS:
      Insertion of tunneled single-lumen Broviac catheters into vessels of the femoral
      triangle or the internal jugular, external jugular, or facial veins by surgical
      cutdown. MEASUREMENTS AND RESULTS: Sixty infants had 2,503 catheter-days with 111
      catheters. Twenty-six infants had 47 femoral catheters, and 34 infants had 64
      jugular catheters. All insertion attempts were successful. The median durations
      of catheter use were 24.0 days and 17.0 days for femoral and jugular catheters,
      respectively (p = 0.021). Group characteristics, insertion variables, incidences
      of complications, and deaths were not significantly different between groups.
      CONCLUSIONS: We conclude that compared to jugular catheters, femoral venous
      Broviac catheters are an effective means to vascular access, with similar
      incidences of complications in newborn infants.

PMID- 12006440
TI  - Upper airway collapsibility during sleep in upper airway resistance syndrome.
AB  - STUDY OBJECTIVES: To compare upper airway collapsibility during sleep between
      patients with upper airway resistance syndrome (UARS), normal subjects, and
      patients with obstructive sleep apnea/hypopnea syndrome (OSA/H). DESIGN: A
      descriptive study of a series of clinical patients and a cohort of normal control
      subjects. SETTING: Two academic sleep-disorders centers. PATIENTS OR
      PARTICIPANTS: One hundred six adult patients with sleep-disordered breathing
      evaluated at the SUNY Sleep Disorders Center-Medicine and 12 adult subjects
      without habitual snoring or daytime sleepiness and with an apnea/hypopnea index
      (AHI) < 5/h evaluated at the Johns Hopkins Pediatric Sleep Disorders Center.
      INTERVENTIONS: All subjects underwent full-night polysomnography and a
      determination of pharyngeal critical pressure (Pcrit). All patients had a
      determination of therapeutic level of nasal continuous positive airway pressure
      (Ptherapeutic). MEASUREMENTS AND RESULTS: The mean +/- SD Pcrit of the 12 normal
      subjects was - 15.4 +/- 6.1 cm H(2)O; the mean Pcrit of the 22 UARS patients was 
      4.0 +/- 2.1 cm H(2)O; the mean Pcrit of the 37 patients with mild-to-moderate
      OSA/H (AHI > or = 10/h and < 40/h) was - 1.6 +/- 2.6 cm H(2)O; and the mean Pcrit
      of the 47 patients with moderate-to-severe OSA/H (AHI > or = 40/h) was 2.4 +/-
      2.8 cm H(2)O. The Pcrit of each group differed from that of all other groups (p <
      0.01). The mean Ptherapeutic of patients with UARS was 6.9 +/- 1.7 cm H(2)O; the
      mean Ptherapeutic of patients with mild-to moderate OSA/H was 7.9 +/- 1.9 cm
      H(2)O (p = 0.08 compared with the Ptherapeutic of UARS patients); and the mean
      Ptherapeutic of patients with moderate-to severe OSA/H was 10.5 +/- 2.4 cm H(2)O
      (p < 0.0001 compared to each of the other patient groups). CONCLUSION: UARS is a
      syndrome of increased upper airway collapsibility during sleep. The upper airway
      collapsibility during sleep of patients with UARS is intermediate between that of
      normal subjects and that of patients with mild-to moderate OSA/H.

PMID- 12006441
TI  - Adhesion molecules in patients with coronary artery disease and moderate-to
      severe obstructive sleep apnea.
AB  - STUDY OBJECTIVES: It has been suggested that obstructive sleep apnea (OSA)
      induced hypoxic stress might contribute to cardiovascular disorders by promoting
      expression of soluble adhesion molecules. The reported increase of circulating
      adhesion molecules in patients with OSA remains controversial because confounders
      such as cardiovascular risk factors and left ventricular function have not been
      adequately controlled for. We hypothesized that soluble intercellular adhesion
      molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and E
      selectin levels are correlated with OSA independent of coexisting coronary artery
      disease (CAD). SETTINGS: University-affiliated teaching hospitals. DESIGN AND
      PARTICIPANTS: A prospective study of 61 consecutive subjects with
      angiographically proven CAD deemed to have stable angina. INTERVENTIONS: Fifteen
      patients (mean +/- SD) 61.2 +/- 1.9 years old with moderate-to-severe OSA (apnea
      hypopnea index [AHI] > or = 20/h) were matched to a control group (AHI < or =
      5/h) for age, gender, body mass index, and severity of CAD. Venous blood samples
      were collected the morning of the sleep study and assayed for human ICAM-1, VCAM
      1, L-selectin, and E-selectin with commercially available enzyme-linked
      immunosorbent assay kits. RESULTS: All but L-selectin were significantly
      increased in the OSA group compared to the control subjects (ICAM-1, 367.4 +/-
      85.2 ng/mL vs 252.8 +/- 68.4 ng/mL, p = 0.008; VCAM-1, 961.5 +/- 281.7 ng/mL vs
      639.1 +/- 294.4 ng/mL, p = 0.004; E-selectin, 81.0 +/- 30.4 ng/mL vs 58.1 +/-
      23.2 ng/mL, p = 0.03, respectively). The increased levels of adhesion molecules
      correlated with the AHI and the oxygen desaturation index but not with the
      severity of hypoxemia or the frequency of arousals. CONCLUSIONS: These findings
      suggest that OSA modulates the expression of proinflammatory mediators. Further
      studies should evaluate the influence of adhesion molecules on cardiovascular
      outcome in CAD patients with OSA.

PMID- 12006442
TI  - Impact of respiratory complications on length of stay and hospital costs in acute
      cervical spine injury.
AB  - CONTEXT: Respiratory complications are frequent in patients with acute cervical
      spinal injury (CSI); however, the importance of respiratory complications
      experienced during the initial hospitalization following injury is unknown.
      OBJECTIVE: To determine if respiratory complications experienced during the
      initial acute-care hospitalization in patients with acute traumatic cervical
      spinal injury (CSI) are more important determinants of the length of stay (LOS)
      and total hospital costs than level of injury. DESIGN: A retrospective analysis
      of an inception cohort for the 5-year period from 1993 to 1997. SETTING: The
      Midwest Regional Spinal Cord Injury Care System, a model system for CSI, at
      Northwestern Memorial Hospital, a tertiary referral academic medical center.
      PATIENTS: Four hundred thirteen patients admitted with acute CSI and discharged
      alive. Patients with concurrent thoracic injuries were excluded. MAIN OUTCOME
      MEASURES: Initial acute-care LOS and hospital costs. RESULTS: Both mean LOS and
      hospital costs increased monotonically with the number of respiratory
      complications experienced (p < 0.001, between none and one complication, and
      between one and two complications; p = 0.24 between two and three or more
      complications). A hierarchical regression analysis showed that four variables-use
      of mechanical ventilation, occurrence of pneumonia, need for surgery, and use of
      tracheostomy-explain nearly 60% of the variance in both LOS and hospital costs.
      Each of these variables, when considered independently, is a better predictor of
      hospital costs than level of injury. CONCLUSIONS: The number of respiratory
      complications experienced during the initial acute-care hospitalization for CSI
      is a more important determinant of LOS and hospital costs than level of injury.

PMID- 12006443
TI  - The effect of noninvasive intermittent positive-pressure ventilation during
      exercise in severe scoliosis.
AB  - STUDY OBJECTIVES: Noninvasive intermittent positive-pressure ventilation (NIPPV)
      may improve exercise performance in COPD patients. It is not known whether this
      also applies to other patient groups such as those with restrictive respiratory
      diseases. DESIGN: Randomized controlled trial. SETTING: Regional center for
      assisted ventilation. SUBJECTS: Eight patients with severe congenital scoliosis.
      INTERVENTIONS: A submaximal treadmill test was performed with NIPPV applied via a
      mouthpiece. Each subject performed three walks breathing with three different
      ventilators and one walk breathing through the mouthpiece alone in random order.
      In addition, four unencumbered walks breathing normally and without monitoring
      were performed. MEASUREMENTS AND RESULTS: The four unencumbered walks did not
      show a significant learning effect. The mean (SD) distance walked was 204 m
      (134.9 m). Using the mouthpiece alone, the walking distance fell to 140 m (75.8
      m), and with the addition of the ventilators it fell further to 109 m (59.3 m).
      Grouped-effects analysis of variance showed this to be a significant difference
      in walking distance according to the type of walk (p = 0.048). There was no
      difference shown among the three brands of ventilator. At the breakpoint of
      exercise, significant increases were seen in tidal volume and minute volume (Mv)
      in the ventilator-assisted walks (p < 0.05) compared to walks performed breathing
      with the mouthpiece alone. CONCLUSIONS: Breathing via a mouthpiece impaired
      exercise performance, and there was no improvement when breathing with a
      ventilator, despite the observed increase in Mv. NIPPV has no beneficial effect
      on exercise endurance in patients with severe scoliosis.

PMID- 12006444
TI  - Transitioning from i.v. epoprostenol to subcutaneous treprostinil in pulmonary
      arterial hypertension.
AB  - OBJECTIVE: Continuous i.v. epoprostenol (prostacyclin) therapy improves survival
      and quality of life in patients with pulmonary arterial hypertension (PAH). i.v.
      epoprostenol therapy may be limited by serious complications related to the need
      for an implanted central venous catheter, and its chemical instability and short
      half-life. Treprostinil is a longer-acting prostacyclin analog, chemically
      stable, and suitable for continuous subcutaneous administration. We report
      successful transitioning to subcutaneous treprostinil of patients who presented
      with life-threatening complications of i.v. epoprostenol delivery. DESIGN: Open,
      uncontrolled study. SETTING: ICUs and departments of cardiology at academic
      hospitals. PATIENTS: Eight patients with PAH treated with continuous i.v.
      epoprostenol. INTERVENTION: Transition to subcutaneous treprostinil following an
      empiric protocol. RESULTS: Transition to treprostinil was achieved successfully
      in 21 to 96 h, with no major adverse side effects, and no change in the improved
      clinical status achieved with i.v. epoprostenol. Doses of epoprostenol before
      transition ranged from 3.5 to 75 ng/kg/min (mean, 27 ng/kg/min). Doses of
      treprostinil at completion of the transition ranged from 3 to 65 ng/kg/min (mean,
      22 ng/kg/min). Four to 11 months later, the patients remained clinically
      improved. In spite of mild-to-moderate infusion site pain, all patients reported
      an improved sense of comfort and well-being. CONCLUSION: Patients with PAH can be
      safely transitioned from treatment with i.v. epoprostenol to subcutaneous
      treprostinil.

PMID- 12006445
TI  - Hemodynamic effects of aerosolized iloprost in pulmonary hypertension at rest and
      during exercise.
AB  - STUDY OBJECTIVES: Aerosolized iloprost, a stable prostacyclin analog, improves
      functional capacity even in patients with pulmonary hypertension who did not show
      a vigorous hemodynamic response after iloprost inhalation at rest. We therefore
      speculated that aerosolized iloprost elicits more beneficial effects on pulmonary
      hemodynamics during exercise than at rest. DESIGN AND SETTING: A prospective,
      open, uncontrolled study at a university hospital. PATIENTS: Sixteen patients
      with primary or secondary pulmonary hypertension. INTERVENTIONS: Right-heart
      catheterization at rest and during exercise before and after the inhalation
      iloprost, 14 to 28 microg. RESULTS: Before iloprost treatment, exercise increased
      mean (+/- SD) pulmonary artery pressure (PAPm) from 45 +/- 8 to 70 +/- 13 mm Hg,
      cardiac output from 3.7 +/- 1.0 to 5.8 +/- 2.4 L/min, and pulmonary vascular
      resistance (PVR) from 904 +/- 322 to 1,013 +/- 432 dyne.s.cm(-5) (each p < 0.05).
      After recovery, iloprost reduced PAPm from 44 +/- 8 to 41 +/- 6 mm Hg, increased
      cardiac output from 3.7 +/- 1.0 to 4.9 +/- 1.4 L/min, and lowered PVR from 902 +/
      350 to 636 +/- 248 dyne x s x cm(-5) (each p < 0.05). During exercise after
      iloprost, PAPm increased to 57 +/- 8 mm Hg, cardiac output to 7.0 +/- 3.0 L/min,
      and PVR to 673 +/- 279 dyne x s x cm(-5) (each p < 0.05 vs first exercise test).
      Systemic BP was not altered significantly by iloprost treatment during exercise.
      CONCLUSIONS: Aerosolized iloprost treatment exerts more favorable effects on
      pulmonary hemodynamics during exercise than at rest. These findings explain the
      functional improvement observed in patients with pulmonary hypertension who show
      only a moderate pulmonary vasodilatory response during iloprost inhalation at
      rest. Whether these beneficial effects have prognostic significance needs to be
      elucidated by further study.

PMID- 12006446
TI  - Oscillatory ventilation during exercise in patients with chronic heart failure:
      clinical correlates and prognostic implications.
AB  - STUDY OBJECTIVES: Although breathing disorders are often found in patients with
      chronic heart failure, exertional oscillatory ventilation (EOV) has been
      occasionally described. The aim of this study was to determine the prevalence,
      clinical characteristics, and outcome of patients with chronic heart failure and
      EOV. SETTING: Cardiology division at tertiary-care hospital. STUDY POPULATION: We
      studied 323 patients with chronic heart failure and left ventricular ejection
      fraction (LVEF) < or = 40%. MEASUREMENTS AND RESULTS: All patients performed a
      symptom-limited cardiopulmonary exercise test and were followed up for 22 +/- 11
      months (mean +/- SD). EOV was defined as cyclic fluctuations in minute
      ventilation (E) at rest that persist during effort lasting > or = 60% of the
      exercise duration, with an amplitude > or = 15% of the average resting value.
      Patients with EOV (12%), as compared to those without, showed higher New York
      Heart Association (NYHA) class (p < 0.05) and lower LVEF (p < 0.0001) and peak
      oxygen consumption (O(2)) [p < 0.0001]. During the follow-up period, 53 patients
      died or underwent urgent cardiac transplantation; this group showed higher NYHA
      class (p < 0.05) and E/CO(2) slope (p < 0.0001) and lower LVEF (p < 0.0001),
      mitral Doppler early deceleration time (p < 0.01), and peak O(2) (p < 0.0001).
      EOV was more frequent in nonsurvivors than in survivors (28% vs 9%, p < 0.01).
      Multivariate analysis revealed peak O(2) (chi(2), 51.5; p < 0.0001), EOV (chi(2),
      45.4; p < 0.0001), and LVEF (chi(2), 20.6; p < 0.0001) as independent predictors
      of major cardiac events. CONCLUSIONS: EOV is not unusual in patients with chronic
      heart failure, and is associated with worse clinical status, cardiac function,
      and exercise capacity. EOV is a powerful predictor of poor prognosis and,
      consequently, it may be considered a valuable guide in the management of patients
      with chronic heart failure and should suggest a more aggressive medical treatment
      policy when detected.

PMID- 12006447
TI  - Prognostic power of ventilatory responses during submaximal exercise in patients
      with chronic heart disease.
AB  - BACKGROUND: Although parameters obtained during submaximal exercise are known to
      be useful for predicting mortality in cardiac patients, it has been a matter of
      debate whether the submaximal parameters are superior to peak oxygen uptake
      (VO(2)). For this purpose, we aimed to determine the best index among exercise
      variables in predicting long-term mortality in patients with chronic heart
      disease. METHODS: The study population consisted of 385 consecutive patients with
      chronic heart disease who performed a symptom-limited incremental exercise test
      on a cycle ergometer. Breath-by-breath respiratory gas analysis was used to
      estimate the peak VO(2), the ratio of the increase in VO(2) to the increase in
      work rate (WR) [VO(2)/Delta WR], and the ratio of the increase in minute
      ventilation E to the increase in carbon dioxide output (VCO(2)) [Delta VE/Delta
      VCO(2)]. RESULTS: After 1,899 +/- 495 days of follow-up (mean +/- SD), 33
      cardiovascular-related deaths occurred. Nonsurvivors achieved lower peak VO(2),
      lower VO(2)/Delta VWR, and higher Delta VE/Delta VCO(2) compared to the
      survivors. In the univariate Cox proportional hazards analysis, peak VO(2),
      VO(2)/Delta VWR, and Delta VE/Delta VCO(2) were found to be significant
      prognostic indexes of survival. However, multivariate analysis revealed
      O(2)/Delta VWR as an independent predictor of mortality and Delta VE/delta VCO(2)
      as a slightly weaker predictor. In this analysis, the prognostic power of peak
      O(2) was insignificant. CONCLUSION: Submaximal respiratory gas indexes are very
      likely to be more sensitive than peak VO(2) for predicting poor survival in
      ambulatory patients with chronic heart disease.

PMID- 12006448
TI  - Elevated serum lipoprotein(a) level is an independent marker of severity of
      thoracic aortic atherosclerosis.
AB  - STUDY OBJECTIVE: Lipoprotein(a) (Lp[a]) level is a risk factor for ischemic heart
      disease, cerebrovascular disease, and peripheral vascular disease. However, few
      data are available concerning the relationship between Lp(a) level and severity
      of thoracic aortic atherosclerosis. We hypothesized in this transesophageal
      echocardiography (TEE) study that Lp(a) level is a marker of severity of thoracic
      aortic atherosclerosis. DESIGN: Cross-sectional study. SETTING: University
      hospital. PATIENTS: Risk factors, coronary angiographic features, and TEE
      findings were analyzed prospectively in 119 patients with valvular disease.
      MEASUREMENTS AND RESULTS: The following risk factors were recorded: age, gender,
      hypertension, smoking, lipid parameters, diabetes, body mass index, and family
      history of coronary artery disease. Serum levels of Lp(a) were measured for each
      patient. By univariate analysis, age, diabetes, hypertension, smoking, Lp(a),
      total cholesterol, low-density lipoprotein cholesterol, and high-density
      lipoprotein cholesterol levels were significant predictors of thoracic aortic
      atherosclerosis. There was a positive and significant correlation between the
      Lp(a) levels and the score of severity of thoracic aortic atherosclerosis (p =
      0.0001). Multivariate regression analysis revealed that Lp(a) was an independent
      predictor of severity of thoracic aortic atherosclerosis (p = 0.0001).
      CONCLUSION: This prospective study indicates that serum Lp(a) level is an
      independent marker of severity of thoracic aortic atherosclerosis detected by
      multiplane TEE. These findings emphasize the role of Lp(a) as a marker of
      atherosclerotic lesions in the major arterial locations.

PMID- 12006449
TI  - Safety of pressure-volume curve measurement in acute lung injury and ARDS using a
      syringe technique.
AB  - STUDY OBJECTIVES: To assess the safety of frequent pressure-volume (PV) curve
      measurement in patients with acute lung injury (ALI)/ARDS. DESIGN: Prospective
      observational study. SETTING: Academic medical-surgical critical care unit.
      PATIENTS: Consecutive patients with ALI or ARDS. INTERVENTIONS: Static
      inspiratory PV curves of the respiratory system were determined twice on day 1,
      then once daily for up to 6 days using a syringe. At each time point, three
      separate measurements of the PV curve were made. A 100-mL graduated syringe was
      used to inflate patients' lungs with 50- to 100-mL increments up to an airway
      pressure of 45 cm H(2)O or a total volume of 2 L; each volume step was maintained
      for 2 to 3 s until a plateau airway pressure was recorded. Outcome measures were
      mean arterial BP, heart rate (HR), and oxyhemoglobin saturation (SpO(2)) prior to
      and immediately after PV curve measurement. There were a priori criteria for
      procedure discontinuation if poorly tolerated. MEASUREMENTS AND RESULTS: Eleven
      patients were enrolled with a total of 134 PV curves generated. SpO(2) was 93 +/-
      4% (mean +/- SD) before and fell to a nadir of 89 +/- 5% during PV curve
      measurement (p < 0.001), but increased to 97 +/- 4% immediately afterwards (p <
      0.001, before vs after). HR rose from 106 +/- 22 to 108 +/- 22 beats/min
      immediately after the maneuver (p < 0.001). Mean arterial BP was 93 +/- 15 mm Hg
      before and 100 +/- 17 mm Hg immediately afterwards (p < 0.001). During PV curve
      measurement, systolic BP in one patient fell to 64 mm Hg from 113 mm Hg; in
      another patient, SpO(2) dropped to 79% from 89%. Both changes were transient. The
      study was discontinued in one patient because of inability to tolerate zero
      positive end-expiratory pressure; in another patient, the study was discontinued
      because of the development of subcutaneous emphysema. CONCLUSIONS: PV curve
      measurement by syringe technique is well tolerated in most patients. Nonetheless,
      the maneuver may cause significant changes in oxygenation and/or hemodynamics,
      necessitating close monitoring.

PMID- 12006450
TI  - The epidemiology of acute respiratory failure in critically ill patients(*).
AB  - STUDY OBJECTIVES: To describe the risk factors for the development of and
      mortality resulting from acute respiratory failure (ARF) in a large patient
      population. DESIGN: A substudy of a prospective, multicenter, observational
      cohort study, which was designed to validate the sequential organ failure
      assessment score. SETTING: Forty ICUs in 16 countries. PATIENTS: All critically
      ill patients who were admitted to one of the participating ICUs during a 1-month
      period were observed until the end of their hospital course. MEASUREMENTS AND
      RESULTS: Of the 1,449 patients who were enrolled into the study, 458 (32%) were
      admitted to an ICU with ARF, as defined by a PaO(2)/fraction of inspired oxygen
      ratio of < 200 mm Hg and the need for respiratory support. Patients who presented
      with ARF were older than the other patients (63 vs 57 years, respectively; p <
      0.001) and more commonly had an infection (47% vs 20%, respectively; p < 0.001).
      The length of ICU stay was longer (6 vs 4 days, respectively; p < 0.001) and the
      ICU mortality rate was more than double (34% vs 16%, respectively; p < 0.001) in
      ARF patients compared to non-ARF patients. Of the 991 patients who were admitted
      to an ICU without ARF, 352 (35%) developed ARF later during the ICU stay. The
      independent risk factors for the development of ARF were infection developing in
      the ICU (odds ratio [OR], 7.59; 95% confidence interval [CI], 5.08 to 11.33) or
      present on ICU admission (OR, 2.3; 95% CI, 1.68 to 3.16), the presence of
      neurologic failure on ICU admission (OR, 2.73; 95% CI, 1.90 to 3.91), and older
      age (OR, 1.70; 95% CI, 1.30 to 2.22). Of all 810 patients with ARF, 253 (31%)
      died. The independent risk factors for death were multiple organ failure
      following ICU admission, history of hematologic malignancy, chronic renal failure
      or liver cirrhosis, the presence of circulatory shock on ICU admission, the
      presence of infection, and older age. CONCLUSIONS: The present study stresses
      that ARF is common in the ICU (56% of all patients) and that a number of
      extrapulmonary factors are related to the risk of development of ARF and to
      mortality rate in these patients.

PMID- 12006451
TI  - Prognostic judgments and triage decisions for patients with acute congestive
      heart failure.
AB  - STUDY OBJECTIVES: To determine how well triage physicians judge the probability
      of death or severe complications that require treatment only available in an ICU
      to maintain life for patients with acute congestive heart failure (CHF). DESIGN:
      Prospective cohort study. SETTING: An urban university hospital, a Veteran's
      Administration hospital, and a community hospital. PATIENTS OR PARTICIPANTS:
      Patients were those visiting the emergency department (ED) with acute CHF,
      excluding those who already required a treatment only available in an ICU to
      maintain life, and those with possible or definite myocardial infarction.
      Physician participants were those caring for the patients in the ED. MEASUREMENTS
      AND RESULTS: We performed chart reviews to ascertain whether each patient died or
      had severe complications develop by 4 days. We collected judgments of the
      probability of this outcome from the physicians taking care of the study patients
      in the ED. The prevalence of death or severe complications was 43 per 1,032
      patients (4.2%). The mean +/- SD of physicians' judgments of the probability of
      this outcome was 32.1 +/- 28.4%. A calibration curve that stratified these
      judgments by decile demonstrated that physicians consistently overestimated this
      probability (p < 0.01). Physicians' judgments were only moderately good at
      discriminating which patients would have the outcome (receiver operating
      characteristic curve area, 0.715). Patients admitted to an ICU received the
      highest average predicted probability (56.4%), followed by those admitted to a
      telemetry unit (34.1%), to a regular hospital ward (29.8%), and those sent home
      (17.9%.) CONCLUSIONS: Physicians drastically overestimated the probability of a
      severe complication that would require critical care for patients with acute CHF
      who were candidates for ICU admission. Their judgments of this probability were
      associated with their triage decisions, as they should be according to several
      guidelines for ICU triage. Overestimation of the probability of severe
      complications may have lead to overutilization of scarce critical care resources.
      Current critical care triage guidelines should be revised to take this difficulty
      into account, and better predictive models for patients potentially requiring
      critical care should be developed.

PMID- 12006452
TI  - Incidence and outcome of polymicrobial ventilator-associated pneumonia.
AB  - STUDY OBJECTIVE: To determine the epidemiology and outcome of polymicrobial
      ventilator-associated pneumonia (VAP). SETTING: Two ICUs (18 and 17 beds) in a
      university hospital. DESIGN AND PATIENTS: We undertook a 16-month study of 124
      patients in whom a first episode of VAP had been diagnosed. Patients in whom
      there was a suspicion of clinical or radiologic VAP underwent bronchoscopy, and
      VAP was confirmed by the presence of at least two of the following criteria: > or
      = 2% of cells with intracellular bacteria found on direct examination of BAL
      fluid (BALF); protected-specimen brush sample culture with > or = 10(3) cfu/mL;
      or BALF culture with > or = 10(4) cfu/mL. RESULTS: Monomicrobial infections were
      diagnosed in 65 patients (52%), and polymicrobial infections were diagnosed in 59
      patients (48%). Two different bacteria were isolated in 42 patients (34%), three
      different bacteria were isolated in 10 patients (8%), and four different bacteria
      were isolated in 7 patients (6%). Patients' clinical characteristics at ICU
      admission and on the day of bronchoscopy were similar, particularly the prior
      duration of mechanical ventilation (MV), the type of ICU admission, disease
      severity scores, and antibiotic therapy received before VAP was diagnosed. The
      percentages of nonfermenting, Gram-negative bacilli and methicillin-resistant
      staphylococci involved in monomicrobial and polymicrobial episodes were similar.
      Furthermore, no significant difference was detected in outcome parameters,
      specifically in the mortality rate at 30 days, the ICU mortality rate, the
      duration of MV, and the rate of infection relapse. CONCLUSION: In our study
      population, the epidemiology and outcomes of patients with monomicrobial and
      polymicrobial VAP did not differ significantly.

PMID- 12006453
TI  - Vascular endothelial growth factor expression in airways of patients with lung
      cancer: a possible diagnostic tool of responsive angiogenic status on the host
      side.
AB  - STUDY OBJECTIVE: We evaluated the expression of vascular endothelial growth
      factor (VEGF) in airways in patients with lung cancer. METHODS: BAL fluid (BALF)
      and plasma samples were obtained from 41 patients with primary lung carcinomas
      and 7 patients with noncancerous diseases, and were analyzed for VEGF by an
      enzyme-linked immunosorbent assay. After standardization with the albumin protein
      levels, the relative intensity (VEGF index) was determined as the ratio of VEGF
      expression on the disease side to that on the healthy side. RESULTS: In all
      cases, VEGF concentrations in BALF were greater than those in plasma samples. On
      the healthy side, the mean value of VEGF in BALF was significantly greater in
      lung cancer patients than in patients with noncancerous diseases (p = 0.0470).
      While age, gender, location of cancer (right vs left), histology (adenocarcinoma
      vs squamous cell carcinoma), and T factor (T1/2 vs T3/4) did not affect the VEGF
      levels in BALF, the VEGF index was inversely associated with distant metastasis
      and nodal involvement. The VEGF index of patients in stage I was significantly
      greater than that of patients in stage IV (p = 0.0308). CONCLUSIONS: The VEGF
      expression in airways is likely to reflect the response to tumor angiogenesis on
      the host side. Of direct clinical relevance is that the assessment of VEGF
      concentrations in airways may provide information concerning the dependency of
      tumor angiogenesis on VEGF, which is variable according to tumor progression.

PMID- 12006454
TI  - Perioperative hemodynamic and geometric changes of the left ventricle during
      cardiomyoplasty in goats with dilated left ventricle.
AB  - OBJECTIVE: Clinical data have suggested the occurrence of temporary short-term
      deterioration of the heart following cardiomyoplasty. The purpose of this study
      was to monitor the short-term hemodynamic effects of cardiomyoplasty in a goat
      model of a dilated left ventricle, using conductance catheters (ie, pressure
      volume loops) and cardiac output measurements. METHODS: Eight female goats
      underwent acute cardiomyoplasty 8 to 12 weeks after left ventricular (LV)
      dilatation was induced by a carotid jugular arteriovenous shunt. The
      cardiomyoplasty procedure was monitored using a Swan-Ganz catheter for cardiac
      output measurements and a 12-electrode (dual-field) conductance catheter to LV
      pressure-volume loops. RESULTS: After wrapping the heart with the latissimus
      dorsi muscle, there was a significant reduction in both cardiac output and LV end
      diastolic volume (LVEDV) at 10 min. Partial recovery was observed 45 min later.
      CONCLUSION: A decrease in both cardiac output and LVEDV was observed following
      myocardial wrapping. This may explain some of the perioperative and postoperative
      morbidity and mortality observed following cardiomyoplasty.

PMID- 12006455
TI  - Stability of frozen methacholine solutions in unit-dose syringes for
      bronchoprovocation.
AB  - OBJECTIVE: Methacholine solutions < 0.25 mg/mL must be prepared fresh daily,
      while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals
      according to US Food and Drug Administration-required labeling. The purpose of
      this report was to determine whether freezing methacholine solutions in unit-dose
      syringes would allow less frequent preparation. DESIGN: Diluent containing 0.5%
      sodium chloride, 0.275% sodium bicarbonate, and 0.4% phenol was used to prepare
      11 concentrations of methacholine ranging from 0.031 to 32.0 mg/mL. Three
      milliliters of each dilution was placed into 5-mL polypropylene syringes and
      immediately frozen. Methacholine concentrations were determined using a validated
      high-performance liquid chromatography assay after preparation (time zero) and at
      0.5, 1, 1.5, 2, 3, 4, 5, and 6 months. On the day of analysis, the samples were
      allowed to thaw to room temperature. An additional set of each dilution was
      stored at room temperature for 24 h after thawing and then analyzed for
      methacholine. RESULTS: Samples > or = 0.062 mg/mL analyzed immediately after
      thawing retained > or = 90% of labeled potency for at least 6 months, while the
      0.031-mg/mL sample retained 90% potency for 4 months. Most samples analyzed 24 h
      after thawing lost potency. CONCLUSION: If prepared and stored in unit-dose
      syringes frozen, methacholine solutions containing 0.062 to 32.0 mg/mL can be
      prepared at 6-month intervals, and solutions containing 0.031 mg/mL can be
      prepared at 4-month intervals. Once thawed, unused methacholine solutions should
      be discarded.

PMID- 12006456
TI  - Alcoholic cardiomyopathy: incidence, clinical characteristics, and
      pathophysiology.
AB  - In the United States, in both sexes and all races, long-term heavy alcohol
      consumption (of any beverage type) is the leading cause of a nonischemic, dilated
      cardiomyopathy, herein referred to as alcoholic cardiomyopathy (ACM). ACM is a
      specific heart muscle disease of a known cause that occurs in two stages: an
      asymptomatic stage and a symptomatic stage. In general, alcoholic patients
      consuming > 90 g of alcohol a day (approximately seven to eight standard drinks
      per day) for > 5 years are at risk for the development of asymptomatic ACM. Those
      who continue to drink may become symptomatic and develop signs and symptoms of
      heart failure. ACM is characterized by an increase in myocardial mass, dilation
      of the ventricles, and wall thinning. Changes in ventricular function may depend
      on the stage, in that asymptomatic ACM is associated with diastolic dysfunction,
      whereas systolic dysfunction is a common finding in symptomatic ACM patients. The
      pathophysiology of ACM is complex and may involve cell death (possibly due to
      apoptosis) and changes in many aspects of myocyte function. ACM remains an
      important cause of a dilated cardiomyopathy, and in latter stages can lead to
      heart failure. Alcohol abstinence, as well as the use of specific heart failure
      pharmacotherapies, is critical in improving ventricular function and outcomes in
      these patients.

PMID- 12006457
TI  - Recent advances in central airway imaging.
AB  - The purpose of this article is to familiarize chest physicians with recent
      advances in airway imaging, with an emphasis on the emerging role of two
      dimensional reformatted and three-dimensional CT reconstructed images in the
      assessment of central airway disorders.

PMID- 12006458
TI  - Strengthening asthma education to enhance disease control.
AB  - This article focuses on reducing the barriers to effectively applying what is
      known about asthma patient education. One barrier to effective asthma control in
      individuals and populations is failure to recognize the range of influences on
      patients trying to manage their disease, including actions of family, clinicians,
      friends and neighbors, work or school mates, and significant people and
      organizations in the wider social environment. Another deterrent is failing to
      assist patients in developing their self-regulation skills. Other barriers are
      the lack of attention to the patients' asthma management goals (as opposed to
      clinical objectives) and overlooking signs that indicate follow-up education is
      needed. Five actions taken by health-care professionals could significantly
      enhance the effectiveness of asthma education: (1) make messages to patients and
      core skills taught consistent with national asthma guidelines; (2) focus on
      developing the patient's ability to self-regulate; (3) develop comprehensive
      plans for treatment and education that assign clinicians to appropriate educative
      roles; (4) use clinician communication techniques demonstrated to enhance asthma
      management by patients; and (5) ensure that all providers of education are
      themselves trained to achieve actions 1 to 4.

PMID- 12006459
TI  - Sinobronchial allergic mycosis: the SAM syndrome.
AB  - We contend that the presence of concomitant allergic fungal sinusitis (AFS) and
      allergic bronchopulmonary mycosis in the same patient represents an expression of
      the same process of fungal hypersensitivity in the upper and lower airways. We
      have termed this process the SAM syndrome, an acronym for sinobronchial allergic
      mycosis. Diagnostic criteria have been established for the SAM syndrome, and the
      clinical characteristics of one previously unreported and four previously
      reported patients have been tabulated. Patients with the SAM syndrome have
      chronic sinusitis involving multiple sinuses, asthma, immediate cutaneous
      reactivity to fungal allergens, peripheral eosinophilia, and radiographic
      evidence of bronchiectasis. Total serum IgE levels are usually elevated as well.
      A variety of chest radiographic abnormalities may occur, ranging from mass
      lesions to diffuse pulmonary infiltrates and even normal findings on chest
      radiographs. Patients present for an evaluation of either sinus or lung disease
      and, at that time, demonstrate no clinical features that distinguish them from
      patients with isolated sinus or lung disease. All patients reported to date have
      had clinical responses to therapy with corticosteroids. We postulate that SAM is
      underdiagnosed in patients with AFS, a disease recently reported from medical
      centers in the southeastern and western United States. Moreover, since our
      patient had a mutation in the cystic fibrosis transmembrane conductor regulator
      (CFTR) gene, we further hypothesize that CFTR gene mutations may play an
      important role in the pathogenesis of the SAM syndrome.

PMID- 12006460
TI  - Diagnostic value of medical thoracoscopy in pleural disease: a 6-year
      retrospective study.
AB  - STUDY OBJECTIVES: Unlike thoracocentesis and closed pleural biopsy (CPB), medical
      thoracoscopy permits biopsy with direct visualization. In a 6-year retrospective
      study of patients having undergone at least one medical thoracoscopy, we analyzed
      the diagnostic yield of thoracoscopy and its value in the management of pleural
      disease. SETTING/PATIENTS: From January 1, 1989, to December 31, 1994, 168
      medical thoracoscopies were performed on 154 patients (123 men; mean age +/- SE,
      61 +/- 1 years), of which 149 were diagnostic and 19 were indicated for
      therapeutic assessment in malignant mesothelioma (MM). Prior to thoracoscopy, at
      least one CPB had been performed in 120 of 149 cases, yielding a diagnosis in 96
      cases. RESULTS: Thoracoscopy challenged the CPB-based diagnosis in 43 of 96
      cases. In 66 cases of nonspecific inflammation diagnosed by CPB, thoracoscopy
      revealed MM in 16 cases, adenocarcinoma in 10 cases, undetermined carcinoma in 3
      cases, and pleural tuberculosis in 3 cases. In 18 cases in which the CPB
      diagnosis was MM, thoracoscopy, performed for precise staging, challenged the
      diagnosis in 4 cases. In 12 cases of carcinoma diagnosed by CPB, thoracoscopy
      specified the histologic type in 7 cases. Thoracoscopic diagnoses were found to
      be erroneous in 10 of 149 cases, mainly owing to pleural adhesions that limited
      access to the pleural cavity. There was one thoracoscopy-related death, one case
      of sepsis, and six cases of empyema. CONCLUSIONS: Medical thoracoscopy appears to
      be efficient and relatively safe in the management of pleural disease. Pleural
      adhesions can lower its diagnostic value.

PMID- 12006461
TI  - Asymptomatic coronary artery disease: choices in evaluation.

PMID- 12006462
TI  - A 47-year-old woman with wheezing and respiratory failure unresponsive to
      conventional ventilatory modalities.

PMID- 12006463
TI  - Anterior chest wall mass in a 46-year-old woman.

PMID- 12006464
TI  - Flexible bronchoscopic management of airway foreign bodies in children.
AB  - OBJECTIVES: To evaluate experience with the flexible bronchoscopic management of
      tracheobronchial foreign bodies (TFBs) in children (age < or = 16 years). DESIGN:
      All pediatric bronchoscopies performed by the bronchoscopy section at Mayo Clinic
      Rochester from 1990 through June 2001 for the suspicion of TFBs were reviewed.
      Information analyzed included the types of bronchoscope (rigid vs flexible) and
      techniques used, success rates of extraction of TFBs, and complications. RESULTS:
      Of the 94 children suspected of having TFBs, 39 children (28 boys and 11 girls;
      mean age, 47.3 months) were found to have 40 TFBs. The flexible bronchoscope was
      used exclusively to extract TFBs in 24 patients, and in 2 patients in whom the
      rigid bronchoscopic procedure was unsuccessful. Flexible bronchoscopy was
      performed through an endotracheal tube in 19 children. In the other five
      children, the procedure was accomplished through a laryngeal mask airway (LMA).
      In two additional patients in whom the rigid bronchoscopic procedure was
      unsuccessful, the instrument served as a conduit for the passage of the flexible
      bronchoscope. The extraction instruments employed included ureteral stone baskets
      and stone forceps. Since 1994, all extractions of TFBs were successfully
      accomplished with the flexible bronchoscope. Complications occurred in four
      patients who underwent rigid bronchoscopy, and included postbronchoscopy
      laryngeal edema manifested by stridor, cough, and respiratory distress. These
      resolved quickly with medical therapy. CONCLUSIONS: Flexible bronchoscopic
      extraction of pediatric TFBs can be performed safely with minimal risks and
      complications. In our experience, it was successful in all children in whom it
      was employed. Nevertheless, we caution that provisions be made to provide
      immediate rigid bronchoscopic management, should the attempts at flexible
      bronchoscopic extraction fail.

PMID- 12006465
TI  - Candy cocaine esophagus.
AB  - Reversible thermal injury to the esophagus from drinking boiling-hot liquids has
      been reported to produce alternating pink and white linear bands that impart a
      "candy-cane" appearance to the inner esophageal wall. This injury has been
      associated with chest pain, dysphagia, odynophagia, and abdominal pain. We
      describe a case of candy-cane esophagus caused by thermal injury from smoking
      freebase cocaine, associated with left shoulder and arm pain, diaphoresis,
      hypotension, and transient cardiac ischemia. This case illustrates the importance
      of considering candy cane esophagus in the evaluation of chest pain, even when
      this symptom is suspected to be of cardiac origin.

PMID- 12006466
TI  - Delayed closure of persistent postpneumonectomy bronchopleural fistula.
AB  - A 73-year-old man with a history of postpneumonectomy empyema and a long-term
      chest tube since 1979 presented with fever, chills, leukocytosis, and purulent
      fluid from the left tube thoracostomy. CT scan and bronchoscopy demonstrated a
      right lower lobe pneumonia and a left mainstem dehiscence with direct
      communication to the left tube thoracostomy. He underwent primary closure of the
      bronchopleural fistula with latissimus dorsi muscle flap coverage after
      antibiotic therapy for right lower lobe pneumonia.

PMID- 12006467
TI  - A "story" of a woman with cystic fibrosis.
AB  - Munchausen syndrome is a pattern of abnormal behavior in which patients
      repeatedly present with symptoms that have no organic basis and are intentionally
      simulated or produced in order to assume the sick role and gain admission to the
      hospital. A 25-year-old white woman presented to our adult cystic fibrosis (CF)
      program and gave a detailed history consistent with a diagnosis of CF, a
      complicated disease with multiorgan involvement that is difficult to feign.
      However, discrepancies in her history were noted and objective measures of
      disease were inconsistent, including evidence of a fabricated sweat chloride
      result. We describe the classic characteristics of Munchausen syndrome that our
      patient exhibited, and report this unusual presentation of Munchausen syndrome to
      be consistent with the recommendation of reporting such cases to other
      physicians. Such knowledge is likely to result in less harm to the patient
      through unnecessary testing and treatment.

PMID- 12006468
TI  - An uncommon mimic of an acute asthma exacerbation.
AB  - Foreign body aspiration in adults has a variety of clinical presentations and
      often goes unrecognized. We describe the case of a patient who experienced crack
      cocaine aspiration and presented with symptoms of an acute asthma exacerbation
      requiring mechanical ventilation until the eventual diagnosis and bronchoscopic
      removal of the foreign body.

PMID- 12006469
TI  - Death associated with rifampin and pyrazinamide 2-month treatment of latent
      mycobacterium tuberculosis.
AB  - We present the case of an elderly patient who died of fulminant hepatic failure
      in the course of receiving 2 months of treatment with pyrazinamide and rifampin
      for his latent tuberculosis. This 2-month course of treatment for latent
      tuberculosis is one of four options recently recommended by the Centers for
      Disease Control and Prevention. We discuss the safety of using this two-drug
      regimen to treat latent tuberculosis in stable elderly patients.

PMID- 12006470
TI  - An unusual case of pneumorrhachis following resection of lung carcinoma.
AB  - We report an unusual case of a patient with a bronchopleural-subcutaneous fistula
      that occurred 3 years following a lobectomy and en bloc chest wall resection for
      carcinoma. Following a sudden resolution of subcutaneous emphysema, an epidural
      air collection developed. Spontaneous pneumorrhachis is a previously unreported
      late complication after surgical or radiation therapy for lung carcinoma.

PMID- 12006471
TI  - Scedosporium apiospermum fungemia in a lung transplant recipient.
AB  - Scedosporium apiospermum, the asexual anamorph of the cosmopolitan fungus
      Pseudallescheria boydii, is emerging as an important cause of disseminated
      infection in immunocompromised patients. We present our experience with the first
      reported case of S apiospermum fungemia in a lung transplant patient.
      Disseminated infection resulted in sepsis, multiorgan failure, and death. Review
      of the literature highlights the diagnostic difficulties related to the
      similarities between S. apiospermum and Aspergillus sp. This superficial
      resemblance has a significant impact on clinical outcomes considering the
      inherent resistance of Scedosporium to amphotericin B, the traditional antifungal
      of choice for disseminated hyalohyphomycoses.

PMID- 12006472
TI  - Common features in the onset of ARDS after administration of granulocyte colony
      stimulating factor.
AB  - STUDY OBJECTIVE: Respiratory disturbance caused by ARDS has been reported during
      administration of granulocyte-colony stimulating factor. The clinical features of
      such respiratory distress were investigated in this study. DESIGN: Retrospective
      case review. SETTING: A 1,100-bed university teaching hospital. PATIENTS: Five
      patients who had dyspnea caused by ARDS develop after chemotherapy or bone marrow
      transplantation (BMT) at our hospital. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Levels of cytokines, human leukocyte antigen (HLA) typing, and the
      clinical course were analyzed to clarify common features. All five patients
      possessed HLA-B51 or HLA-B52, and all had fever and an enhanced inflammatory
      response at the time of the WBC nadir. The tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-8 levels increased when respiratory distress syndrome occurred.
      CONCLUSIONS: If patients with HLA-B51 or HLA-B52 have infection develop at the
      time of WBC nadir after chemotherapy or BMT, ARDS may occur in association with
      elevation of TNF-alpha and IL-8 during WBC recovery.

PMID- 12006473
TI  - Detection of COPD in high-risk populations.

PMID- 12006474
TI  - Pediatric primary pulmonary tuberculosis.

PMID- 12006475
TI  - Vasopressin and cardiac performance.

PMID- 12006476
TI  - Exhaled carbon monoxide in COPD.

PMID- 12006477
TI  - Usefulness of methemoglobin/haptoglobin analysis in the follow-up of severe
      immune hemolytic anemia.

PMID- 12006478
TI  - CT screening for early stage lung cancer.

PMID- 12006479
TI  - Predictive parameters of dropout during inhaled corticosteroid tapering.

PMID- 12006480
TI  - Adequate tidal volume with row-a-boat phenomenon in advanced Duchenne muscular
      dystrophy.

PMID- 12006483
TI  - T-cell factors: turn-ons and turn-offs.

PMID- 12006484
TI  - A novel mode of sensory transduction in archaea: binding protein-mediated
      chemotaxis towards osmoprotectants and amino acids.
AB  - Directly upstream of the Halobacterium salinarum transducer genes basT and htpIV
      we identified two open reading frames (orfs) with significant homologies to genes
      encoding binding proteins for amino acids and compatible solutes, respectively.
      Behavioral testing of deletion mutants indicates that halobacterial chemotaxis
      towards branched-chain amino acids as well as compatible osmolytes of the betaine
      family requires both a binding and a transducer protein. We therefore named the
      binding/transducer proteins BasB/BasT for branched-chain and sulfur-containing
      amino acids and CosB/CosT for compatible solutes. Our data support a signaling
      mechanism with the binding proteins functioning as lipid-anchored receptors
      interacting with the extracellular domain of their cognate transducers.
      Inspection of the halobacterial genome suggests that BasB and CosB exclusively
      mediate chemotaxis responses without any additional role in transport, which is
      in contrast to bacterial binding proteins, which are always part of ABC transport
      systems. The CosB/CosT system is the first instance of a chemotaxis signaling
      pathway for organic osmolytes in the living world and natural abundance 13C-NMR
      analysis of cytoplasmic extracts suggests that H.salinarum utilizes these solutes
      for osmotic adaptation.

PMID- 12006485
TI  - Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via
      target mimicry.
AB  - The misuse of antibiotics has selected for bacteria that have evolved mechanisms
      for evading the effects of these drugs. For aminoglycosides, a group of
      clinically important bactericidal antibiotics that target the A-site of the 16S
      ribosomal RNA, the most common mode of resistance is enzyme-catalyzed chemical
      modification of the drug. While aminoglycosides are structurally diverse, a
      single enzyme can confer resistance to many of these antibiotics. For example,
      the aminoglycoside kinase APH(3')-IIIa, produced by pathogenic Gram-positive
      bacteria such as enterococci and staphylococci, is capable of detoxifying at
      least 10 distinct aminoglycosides. Here we describe the crystal structures of
      APH(3')-IIIa in complex with ADP and kanamycin A or neomycin B. These structures
      reveal that the basis for this enzyme's substrate promiscuity is the presence of
      two alternative subsites in the antibiotic binding pocket. Furthermore,
      comparison between the A-site of the bacterial ribosome and APH(3')-IIIa shows
      that mimicry is the second major factor in dictating the substrate spectrum of
      APH(3')-IIIa. These results suggest a potential strategy for drug design aimed at
      circumventing antibiotic resistance.

PMID- 12006486
TI  - Synaptic multiprotein complexes associated with 5-HT(2C) receptors: a proteomic
      approach.
AB  - Membrane-bound receptors such as tyrosine kinases and ionotropic receptors are
      associated with large protein networks structured by protein-protein interactions
      involving multidomain proteins. Although these networks have emerged as a general
      mechanism of cellular signalling, much less is known about the protein complexes
      associated with G-protein-coupled receptors (GPCRs). Using a proteomic approach
      based on peptide affinity chromatography followed by mass spectrometry and
      immunoblotting, we have identified 15 proteins that interact with the C- terminal
      tail of the 5-hydroxytryptamine 2C (5-HT(2C)) receptor, a GPCR. These proteins
      include several synaptic multidomain proteins containing one or several PDZ
      domains (PSD95 and the proteins of the tripartite complex Veli3-CASK-Mint1),
      proteins of the actin/spectrin cytoskeleton and signalling proteins.
      Coimmunoprecipitation experiments showed that 5-HT(2C) receptors interact with
      PSD95 and the Veli3-CASK-Mint1 complex in vivo. Electron microscopy also
      indicated a synaptic enrichment of Veli3 and 5-HT(2C) receptors and their
      colocalization in microvilli of choroidal cells. These results indicate that the
      5-HT(2C) receptor is associated with protein networks that are important for its
      synaptic localization and its coupling to the signalling machinery.

PMID- 12006487
TI  - Essential role of calcineurin in response to endoplasmic reticulum stress.
AB  - Depletion of calcium ions (Ca2+) from the endoplasmic reticulum (ER) of yeast
      cells resulted in the activation of the unfolded protein response (UPR) signaling
      pathway involving Ire1p and Hac1p. The depleted ER also stimulated Ca2+ influx at
      the plasma membrane through the Cch1p-Mid1p Ca2+ channel and another system.
      Surprisingly, both Ca2+ influx systems were stimulated upon accumulation of
      misfolded proteins in the ER even in the presence of Ca2+. The ability of
      misfolded ER proteins to stimulate Ca2+ influx at the plasma membrane did not
      require Ire1p or Hac1p, and Ca2+ influx and signaling factors were not required
      for initial UPR signaling. However, activation of the Ca2+ channel, calmodulin,
      calcineurin and other factors was necessary for long-term survival of cells
      undergoing ER stress. A similar calcium cell survival (CCS) pathway operates in
      the pathogenic fungi and promotes resistance to azole antifungal drugs. These
      findings reveal an unanticipated new regulatory mechanism that couples ER stress
      to Ca2+ influx and signaling pathways, which help to prevent cell death and
      promote resistance to an important class of fungistatic drugs.

PMID- 12006488
TI  - Four cysteines of the membrane protein DsbB act in concert to oxidize its
      substrate DsbA.
AB  - Protein disulfide bond formation in Escherichia coli is catalyzed by the
      periplasmic protein DsbA. A cytoplasmic membrane protein DsbB maintains DsbA in
      the oxidized state by transferring electrons from DsbA to quinones in the
      respiratory chain. Here we show that DsbB activity can be reconstituted by co
      expression of N- and C-terminal fragments of the protein, each containing one of
      its redox-active disulfide bonds. This system has allowed us (i) to demonstrate
      that the two DsbB redox centers interact directly through a disulfide bond formed
      between the two DsbB domains and (ii) to identify the specific cysteine residues
      involved in this covalent interaction. Moreover, we are able to capture an
      intermediate in the process of electron transfer from one redox center to the
      other. These results lead us to propose a model that describes how the cysteines
      cooperate in the early stages of oxidation of DsbA. DsbB appears to adopt a novel
      mechanism to oxidize DsbA, using its two pairs of cysteines in a coordinated
      reaction to accept electrons from the active cysteines in DsbA.

PMID- 12006489
TI  - Polyploid measles virus with hexameric genome length.
AB  - Particles of most virus species accurately package a single genome, but there are
      indications that the pleomorphic particles of parainfluenza viruses incorporate
      multiple genomes. We characterized a stable measles virus mutant that efficiently
      packages at least two genomes. The first genome is recombinant and codes for a
      defective attachment protein with an appended domain interfering with fusion
      support function. The second has one adenosine insertion in a purine run that
      interrupts translation of the appended domain and restores function. In that
      genome, a one base deletion in a different purine run abolishes polymerase
      synthesis, but restores hexameric genome length, thus ensuring accurate RNA
      encapsidation, which is necessary for efficient replication. Thus, the two
      genomes are complementary. The infection kinetics of this mutant indicate that
      packaging of multiple genomes does not negatively affect growth. We also show
      that polyploid particles are produced in standard infections at no expense to
      infectivity. Our results illustrate how the particles of parainfluenza viruses
      efficiently accommodate cargoes of different volume, and suggest a mechanism by
      which segmented genomes may have evolved.

PMID- 12006490
TI  - Regulation of Cdc42-mediated morphological effects: a novel function for p53.
AB  - The tumour suppressor functions of p53 that are important for its activity depend
      on its role as a cell cycle arrest mediator and apoptosis inducer. Here we
      identify a novel function for p53 in regulating cell morphology and movement. We
      investigated the overall effect of p53 on morphological changes induced by RhoA,
      Rac1 and Cdc42 GTPases in mouse embryonic fibroblasts (MEFs). Interestingly, p53
      exerted a selective effect on Cdc42-mediated cell functions. (i) Both
      overexpression of wild-type p53 and activation of endogenous p53 counteracted
      Cdc42-induced filopodia formation. Conversely, p53-deficient MEFs exhibited
      constitutive membrane filopodia. Mechanistic studies indicate that p53 prevents
      the initiating steps of filopodia formation downstream of Cdc42. (ii) Over
      expression of p53 modulates cell spreading of MEFs on fibronectin. (iii) During
      cell migration, the reorientation of the Golgi apparatus in the direction of
      movement is abolished by wild-type p53 expression, thus preventing cell polarity.
      Our data demonstrate a previously uncharacterized role for p53 in regulating
      Cdc42-dependent cell effects that control actin cytoskeletal dynamics and cell
      movement. This novel function may contribute to p53 anti-tumour activity.

PMID- 12006491
TI  - Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence.
AB  - The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD
      dependent histone deacetylase activity. Sir2 is a conserved protein and was
      recently shown to regulate lifespan extension both in budding yeast and worms.
      Here, we show that SIRT1, the human Sir2 homolog, is recruited to the
      promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon
      overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and
      deacetylates p53, a component of PML nuclear bodies, and it can repress p53
      mediated transactivation. Moreover, we show that SIRT1 and p53 co-localize in
      nuclear bodies upon PML upregulation. When overexpressed in primary mouse embryo
      fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues
      PML-mediated premature cellular senescence. Taken together, our data establish
      the SIRT1 deacetylase as a novel negative regulator of p53 function capable of
      modulating cellular senescence.

PMID- 12006492
TI  - Structure and functional interactions of the Tsg101 UEV domain.
AB  - Human Tsg101 plays key roles in HIV budding and in cellular vacuolar protein
      sorting (VPS). In performing these functions, Tsg101 binds both ubiquitin (Ub)
      and the PTAP tetrapeptide 'late domain' motif located within the viral Gag
      protein. These interactions are mediated by the N-terminal domain of Tsg101,
      which belongs to the catalytically inactive ubiquitin E2 variant (UEV) family. We
      now report the structure of Tsg101 UEV and chemical shift mapping of the Ub and
      PTAP binding sites. Tsg101 UEV resembles canonical E2 ubiquitin conjugating
      enzymes, but has an additional N-terminal helix, an extended beta-hairpin that
      links strands 1 and 2, and lacks the two C-terminal helices normally found in E2
      enzymes. PTAP-containing peptides bind in a hydrophobic cleft exposed by the
      absence of the C-terminal helices, whereas ubiquitin binds in a novel site
      surrounding the beta-hairpin. These studies provide a structural framework for
      understanding how Tsg101 mediates the protein-protein interactions required for
      HIV budding and VPS.

PMID- 12006493
TI  - Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases:
      implications for cancer therapy.
AB  - Overexpression of ErbB-2/HER2 is associated with aggressive human malignancies,
      and therapeutic strategies targeting the oncoprotein are currently in different
      stages of clinical application. Tyrosine kinase inhibitors (TKIs) that block the
      nucleotide-binding site of the kinase are especially effective against tumors.
      Here we report an unexpected activity of TKIs: along with inhibition of tyrosine
      phosphorylation, they enhance ubiquitylation and accelerate endocytosis and
      subsequent intracellular destruction of ErbB-2 molecules. Especially potent is an
      irreversible TKI (CI-1033) that alkylates a cysteine specific to ErbB receptors.
      The degradative pathway stimulated by TKIs appears to be chaperone mediated, and
      is common to the heat shock protein 90 (Hsp90) antagonist geldanamycin and a
      stress-induced mechanism. In agreement with this conclusion, CI-1033 and
      geldanamycin additively inhibit tumor cell growth. Based upon a model for drug
      induced degradation of ErbB-2, we propose a general strategy for selective
      destruction of oncoproteins by targeting their interaction with molecular
      chaperones.

PMID- 12006494
TI  - Ubiquitylation of MHC class I by the K3 viral protein signals internalization and
      TSG101-dependent degradation.
AB  - The Kaposi's sarcoma-associated herpes virus gene product K3 (KK3) subverts the
      MHC class I antigen presentation pathway by downregulating MHC class I from the
      plasma membrane. We now show that KK3 associates with MHC class I molecules and
      promotes ubiquitylation of class I after export from the endoplasmic reticulum.
      Ubiquitylation requires the KK3 N-terminal plant homeodomain and provides the
      signal for class I internalization at the plasma membrane. Once internalized,
      ubiquitylated MHC class I is targeted to the late endocytic pathway, where it is
      degraded. Depletion by small interfering RNA of TSG101, a ubiquitin enzyme 2
      variant protein involved in late endosomal sorting, prevents class I degradation
      and preserves cell surface class I expression in KK3-expressing cells. These
      results suggest a mechanism by which the KK3-induced class I ubiquitylation
      provides a signal for both internalization and sorting to the late endosomal
      pathway for degradation. KK3 is the first viral gene product that subverts the
      trafficking of a host protein via the ubiquitin-dependent endosomal sorting
      machinery.

PMID- 12006495
TI  - The dMi-2 chromodomains are DNA binding modules important for ATP-dependent
      nucleosome mobilization.
AB  - Drosophila Mi-2 (dMi-2) is the ATPase subunit of a complex combining ATP
      dependent nucleosome remodelling and histone deacetylase activities. dMi-2
      contains an HMG box-like region, two PHD fingers, two chromodomains and a SNF2
      type ATPase domain. It is not known which of these domains contribute to
      nucleosome remodelling. We have tested a panel of dMi-2 deletion mutants in
      ATPase, nucleosome mobilization and nucleosome binding assays. Deletion of the
      chromodomains impairs all three activities. A dMi-2 mutant lacking the
      chromodomains is incorporated into a functional histone deacetylase complex in
      vivo but has lost nucleosome-stimulated ATPase activity. In contrast to dHP1, dMi
      2 does not bind methylated histone H3 tails and does not require histone tails
      for nucleosome binding. Instead, the dMi-2 chromodomains display DNA binding
      activity that is not shared by other chromodomains. Our results suggest that the
      chromodomains act at an early step of the remodelling process to bind the
      nucleosome substrate predominantly via protein-DNA interactions. Furthermore, we
      identify DNA binding as a novel chromodomain-associated activity.

PMID- 12006496
TI  - PIF4, a phytochrome-interacting bHLH factor, functions as a negative regulator of
      phytochrome B signaling in Arabidopsis.
AB  - Plants sense and respond to red and far-red light using the phytochrome (phy)
      family of photoreceptors. However, the mechanism of light signal transduction is
      not well defined. Here, we report the identification of a new mutant Arabidopsis
      locus, srl2 (short under red-light 2), which confers selective hypersensitivity
      to continuous red, but not far-red, light. This hypersensitivity is eliminated in
      srl2phyB, but not srl2phyA, double mutants, indicating that this locus functions
      selectively and negatively in phyB signaling. The SRL2 gene encodes a bHLH
      factor, designated PIF4 (phytochrome-interacting factor 4), which binds
      selectively to the biologically active Pfr form of phyB, but has little affinity
      for phyA. Despite its hypersensitive morphological phenotype, the srl2 mutant
      displays no perturbation of light-induced expression of marker genes for
      chloroplast development. These data suggest that PIF4 may function specifically
      in a branch of the phyB signaling network that regulates a subset of genes
      involved in cell expansion. Consistent with this proposal, PIF4 localizes to the
      nucleus and can bind to a G-box DNA sequence motif found in various light
      regulated promoters.

PMID- 12006497
TI  - Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of
      TIEG2, an Sp1-like repressor.
AB  - A Sin3-interacting domain (SID) originally described in Mad proteins is necessary
      for both transcriptional repression and growth suppression by these transcription
      factors. We recently reported that a structurally and functionally related Mad1
      like SID is also present in five Sp1-like repressor proteins (TIEG1, TIEG2,
      BTEB1, BTEB3 and BTEB4), demonstrating that SID-mSin3A interactions have a wider
      functional impact on transcriptional repression. SID-mSin3A interaction is
      necessary for the anti-proliferative function of Mad, TIEG and BTEB proteins. It
      remains to be established, however, whether the SID-mSin3A interaction is
      constitutive or regulated. Here, we describe that the Mad1-like SID domain of the
      Sp1-like repressor TIEG2 is inhibited by the epidermal growth factor (EGF)-Ras
      MEK1-ERK2 signaling pathway, via phosphorylation of four serine/threonine sites
      adjacent to the SID. This phenomenon disrupts the SID-mSin3A interaction and
      thereby inhibits TIEG2's repression activity. Thus, these results show for the
      first time that the repression of a SID-containing protein is regulated by
      signaling rather than functioning in a constitutive manner, extending our
      understanding of how the function of SID-containing repressors may be controlled.

PMID- 12006498
TI  - The global structure of the VS ribozyme.
AB  - The VS ribozyme comprises five helical segments (II-VI) in a formal H shape,
      organized by two three-way junctions. It interacts with its stem-loop substrate
      (I) by tertiary interactions. We have determined the global shape of the 3-4-5
      junction (relating helices III-V) by electrophoresis and FRET. Estimation of the
      dihedral angle between helices II and V electrophoretically has allowed us to
      build a model for the global structure of the complete ribozyme. We propose that
      the substrate is docked into a cleft between helices II and VI, with its loop
      making a tertiary interaction with that of helix V. This is consistent with the
      dependence of activity on the length of helix III. The scissile phosphate is well
      placed to interact with the probable active site of the ribozyme, the loop
      containing A730.

PMID- 12006499
TI  - The existence of two distinct Wee1 isoforms in Xenopus: implications for the
      developmental regulation of the cell cycle.
AB  - In eukaryotic cells, the Wee1 protein kinase phosphorylates and inhibits Cdc2,
      thereby creating an interphase of the cell cycle. In Xenopus, the conventional
      Wee1 homolog (termed Xe-Wee1A, or Wee1A for short) is maternally expressed and
      functions in pregastrula embryos with rapid cell cycles. Here, we have isolated a
      second, zygotic isoform of Xenopus Wee1, termed Xe-Wee1B (or Wee1B for short),
      that is expressed in postgastrula embryos and various adult tissues. When
      ectopically expressed in immature oocytes, Wee1B inhibits Cdc2 activity and
      oocyte maturation (or entry into M phase) much more strongly than Wee1A, due to
      its short C-terminal regulatory domain. Moreover, ectopic Wee1B, unlike Wee1A, is
      very labile during meiosis II and cannot accumulate in mature oocytes due to the
      presence of PEST-like sequences in its N-terminal regulatory domain. Finally,
      when expressed in fertilized eggs, ectopic Wee1B but not Wee1A does affect cell
      division and impair cell viability in early embryos, due primarily to its very
      strong kinase activity. These results suggest strongly that the differential
      expression of Wee1A and Wee1B is crucial for the developmental regulation of the
      cell cycle in Xenopus.

PMID- 12006500
TI  - Cell cycle-dependent dynamic association of cyclin/Cdk complexes with human DNA
      replication proteins.
AB  - We have previously described the isolation of a replication competent (RC)
      complex from calf thymus, containing DNA polymerase alpha, DNA polymerase delta
      and replication factor C. Here, we describe the isolation of the RC complex from
      nuclear extracts of synchronized HeLa cells, which contains DNA replication
      proteins associated with cell-cycle regulation factors like cyclin A, cyclin B1,
      Cdk2 and Cdk1. In addition, it contains a kinase activity and DNA polymerase
      activities able to switch from a distributive to a processive mode of DNA
      synthesis, which is dependent on proliferating cell nuclear antigen. In vivo
      cross-linking of proteins to DNA in synchronized HeLa cells demonstrates the
      association of this complex to chromatin. We show a dynamic association of
      cyclins/Cdks with the RC complex during the cell cycle. Indeed, cyclin A and Cdk2
      associated with the complex in S phase, and cyclin B1 and Cdk1 were present
      exclusively in G(2)/M phase, suggesting that the activity, as well the
      localization, of the RC complex might be regulated by specific cyclin/Cdk
      complexes.

PMID- 12006501
TI  - Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a
      'safety belt' binding mechanism for the spindle checkpoint.
AB  - The spindle checkpoint protein Mad1 recruits Mad2 to unattached kinetochores and
      is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. The
      crystal structure of the Mad1-Mad2 complex reveals an asymmetric tetramer, with
      elongated Mad1 monomers parting from a coiled-coil to form two connected sub
      complexes with Mad2. The Mad2 C-terminal tails are hinged mobile elements
      wrapping around the elongated ligands like molecular 'safety belts'. We show that
      Mad1 is a competitive inhibitor of the Mad2-Cdc20 complex, and propose that the
      Mad1-Mad2 complex acts as a regulated gate to control Mad2 release for Cdc20
      binding. Mad1-Mad2 is strongly stabilized in the tetramer, but a 1:1 Mad1-Mad2
      complex slowly releases Mad2 for Cdc20 binding, driven by favourable binding
      energies. Thus, the rate of Mad2 binding to Cdc20 during checkpoint activation
      may be regulated by conformational changes that destabilize the tetrameric Mad1
      Mad2 assembly to promote Mad2 release. We also show that unlocking the Mad2 C
      terminal tail is required for ligand release from Mad2, and that the 'safety
      belt' mechanism may prolong the lifetime of Mad2-ligand complexes.

PMID- 12006504
TI  - Approval summary for imatinib mesylate capsules in the treatment of chronic
      myelogenous leukemia.
AB  - PURPOSE: Chronic myelogenous leukemia (CML) results from the breakpoint cluster
      region-Abl fusion gene product, a tyrosine kinase involved in cell division and
      apoptosis. Imatinib, an orally administered inhibitor of the breakpoint cluster
      region-Abl tyrosine kinase, is capable of blocking proliferation and inducing
      apoptosis in CML cell lines. In this report, we describe the preclinical profile
      of imatinib and the data submitted in the New Drug Application that led to its
      marketing approval. EXPERIMENTAL DESIGN: Chemistry manufacturing and controls,
      animal toxicology, and biopharmaceutical data are described. Results of Phase I
      and Phase II clinical studies in patients with CML in blast crisis (CML-BC), in
      accelerated phase (CML-AP), and in chronic phase disease-resistant or intolerant
      to IFN-alpha (CML-CP) are summarized. The basis for marketing approval and
      postmarketing commitments by the pharmaceutical company are discussed. RESULTS:
      Toxicology studies in the rat, dog, and monkey show the hematological, renal, and
      hepatobiliary toxicity of imatinib. Pharmacokinetic studies in patients with CML
      demonstrate 98% imatinib bioavailability. The elimination half-lives of the
      parent drug and the major active metabolite, CGP74588, from plasma are
      approximately 18 and 40 h, respectively. Approximately 81% of the drug is
      eliminated in 7 days, 68% in the feces and 13% in the urine. Cytochrome P-450 3A4
      is the main enzyme responsible for imatinib metabolism. Phase I and II clinical
      studies were conducted. The Phase I study, in 83 CML patients, evaluated oral
      imatinib doses from 25 to 1000 mg/day. Dose-limiting toxicity was not observed.
      The three Phase II studies, in CML-CP, CML-AP, and CML-BC, enrolled 1027
      patients. CML-CP patients received 400 mg/day imatinib, whereas CML-AP and CML-BC
      patients generally received 600 mg/day imatinib. Primary study endpoints were
      cytogenetic response rate (CML-CP) and hematological response rate (CML-AP and
      CML-BC). The cytogenetic response rate for CML-CP patients was 49%. The
      hematological response rate of CML-AP and CML-BC patients was 63 and 26%,
      respectively. The most common imatinib adverse events were nausea, vomiting,
      myalgia, edema, and diarrhea. Elevated liver enzymes and/or bilirubin were
      reported in 27 patients (2.6%). CONCLUSIONS: On May 10, 2001, imatinib mesylate
      (Gleevec, formerly known as STI-571 and Glivec), manufactured and distributed by
      Novartis Pharmaceuticals, East Hanover, NJ, was approved by the United States
      Food and Drug Administration for the treatment of CML in three clinical settings:
      CML-BC, CML-AP, and CML-CP. This report summarizes the Food and Drug
      Administration's review of the New Drug Application.

PMID- 12006505
TI  - Cooperative group tissue banks as research resources: the cancer and leukemia
      group B tissue repositories.

PMID- 12006506
TI  - Transcription factors and neoplasia: vistas in novel drug design.
AB  - PURPOSE: The fundamental role of gene transcription and the recognition of
      transcription factors as important control elements of cell growth,
      differentiation, and programmed cell death (apoptosis) aroused an ever-increasing
      interest for these proteins as potential pharmaceutical targets for therapeutic
      intervention in various diseases, among them cancer. EXPERIMENTAL DESIGN-RESULTS:
      The vast array of information available for their molecular architecture and mode
      of action in various biological contexts, combined with the new opportunities
      offered by the flourishing technologies of structure-based drug design, computer
      aided modeling, and functional genomics/proteomics, are creating an exciting
      scenery for the development of a novel generation of highly selective drugs.
      CONCLUSIONS: This transcription factor-based therapeutic approach may
      revolutionize the anticancer drug options and will add significantly to the
      current clinical armamentarium.

PMID- 12006507
TI  - Heat shock protein 90 inhibition by 17-allylamino-17- demethoxygeldanamycin: a
      novel therapeutic approach for treating hormone-refractory prostate cancer.

PMID- 12006508
TI  - T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma
      patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte
      macrophage colony-stimulating factor, and QS-21 as immunological adjuvants.
AB  - We conducted a randomized trial in HLA*A0201+ patientswith American Joint
      Committee on Cancer stage III or IV melanoma immunized with tyrosinase 368
      376(370D) peptide and gp100 209-217(210M) peptide to compare the potency of three
      different adjuvants. Patients received 3 monthly immunizations with 500 microg of
      each peptide either with incomplete Freund's adjuvant (IFA), QS-21, or
      granulocyte macrophage colony-stimulating factor (GM-CSF). The primary end point
      was induction of IFN-gamma release by CD8+ T cells against tyrosinase and gp100
      peptides measured by enzyme-linked immunospot assays without in vitro
      prestimulation measured pretreatment, 2 and 8 weeks after the third vaccination.
      Four of 9 and 4 of 8 patients immunized using QS-21 and GM-CSF, respectively,
      developed increased frequencies of CD8+ T cells against tyrosinase 370D peptide
      compared with 0 of 9 patients immunized using IFA (P = 0.045). T-cell responses
      against a gp100-related peptide showed similar results, but their relevance to T
      cell reactivity against native gp100 209-217 is uncertain. These results show
      that: (a) QS-21 and GM-CSF are superior to IFA as immunological adjuvants for
      vaccination against tyrosinase 370D peptide; and (b) with appropriate adjuvants,
      increased frequencies of peptide-specific T cells after vaccination can be
      detected by enzyme-linked immunospot without prolonged prestimulation in vitro.

PMID- 12006509
TI  - p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer.
AB  - PURPOSE: Although p53 mutations occur in alkylating agent-related leukemias,
      their frequency and spectrum in leukemias after ovarian cancer have not been
      addressed. The purpose of this study was to examine p53 mutations in leukemias
      after ovarian cancer, for which treatment with platinum analogues was widely
      used. EXPERIMENTAL DESIGN: Adequate leukemic or dysplastic cells were available
      in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a
      multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven
      of the 17 received platinum compounds and other alkylating agents with or without
      DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating
      agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5,
      6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were
      analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by
      sequencing. RESULTS: Eleven p53 mutations involving all four exons studied and
      one polymorphism were identified. Genomic DNA analyses were consistent with loss
      of heterozygosity for four of the mutations. The 11 mutations occurred in 9
      cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6
      leukemias after other treatments (50%) contained p53 mutations. Two leukemias
      that occurred after treatment with platinum analogues contained two mutations.
      Among eight mutations in leukemias after treatment with platinum analogues, there
      were four G-to-A transitions and one G-to-C transversion. CONCLUSIONS: p53
      mutations are common in leukemia and myelodysplastic syndrome after multiagent
      therapy for ovarian cancer. The propensity for G-to-A transitions may reflect
      specific DNA damage in leukemias after treatment with platinum analogues.

PMID- 12006510
TI  - 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen
      receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts.
AB  - PURPOSE: Ansamycin antibiotics, including 17allylamino-17-demethoxygeldanamycin
      (17-AAG), inhibit Hsp90 function and cause the selective degradation of signaling
      proteins that require this chaperone for folding. Because mutations in the
      androgen receptor (AR) and activation of HER2 and Akt may account, in part, for
      prostate cancer progression after castration or treatment with antiandrogens, we
      sought to determine whether an inhibitor of Hsp90 function could degrade these
      Hsp90 client proteins and inhibit the growth of prostate cancer xenografts with
      an acceptable therapeutic index. EXPERIMENTAL DESIGN: The effect of 17-AAG on the
      expression of Hsp90 regulated signaling proteins in prostate cancer cells and
      xenografts was determined. The pharmacodynamics of target protein degradation was
      associated with the toxicology and antitumor activity of the drug. RESULTS: 17
      AAG caused the degradation of HER2, Akt, and both mutant and wild-type AR and the
      retinoblastoma-dependent G1 growth arrest of prostate cancer cells. At nontoxic
      doses, 17-AAG caused a dose-dependent decline in AR, HER2, and Akt expression in
      prostate cancer xenografts. This decline was rapid, with a 97% loss of HER2 and
      an 80% loss of AR expression at 4 h. 17-AAG treatment at doses sufficient to
      induce AR, HER2, and Akt degradation resulted in the dose-dependent inhibition of
      androgen-dependent and -independent prostate cancer xenograft growth without
      toxicity. CONCLUSIONS: These data demonstrate that, at a tolerable dose,
      inhibition of Hsp90 function by 17-AAG results in a marked reduction in HER2, AR,
      and Akt expression and inhibition of prostate tumor growth in mice. These results
      suggest that this drug may represent a new strategy for the treatment of prostate
      cancer.

PMID- 12006511
TI  - Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal
      antibody IMC-C225 in combination with irinotecan (CPT-11) against human
      colorectal tumor xenografts.
AB  - Colon carcinomas frequently express the epidermal growth factor receptor (EGFR),
      and this expression correlates with more aggressive disease and poor prognosis.
      Previous studies have shown that EGFR blockade by monoclonal antibody IMC-C225
      can inhibit the growth of human colon carcinoma tumor cells in vitro and
      xenografts of these tumors in athymic mice. In this report, we have studied the
      in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor
      irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice.
      IMC-C225 was tested at a dose of 1 or 0.5 mg administered q3d. CPT-11 was
      administered at a dose of 100 mg/kg/week or a maximum tolerated dose of 150
      mg/kg/week. Treatment with the combination of IMC-C225 (1 and 0.5 mg) and CPT-11
      (100 mg/kg) significantly inhibited the growth of established DLD-1 and HT-29
      tumors compared with either CPT-11 or IMC-C225 monotherapy (P < 0.05).
      Combination therapy with IMC-C225 (1 mg) and the MTD of CPT-11 (150 mg/kg)
      resulted in a regression rate of 100 and 60% of established DLD-1 and HT-29
      tumors, respectively. In a refractory tumor model, combined treatment with IMC
      C225 and CPT-11 significantly inhibited the growth of CPT-11 refractory DLD-1 and
      HT-29 tumors, whereas either agent alone did not control tumor growth.
      Histological examination of treated tumors showed extensive tumor necrosis,
      decreased tumor cell proliferation, increased tumor cell apoptosis, and a marked
      decrease in tumor vasculature. These results suggest that EGFR blockade by IMC
      C225 combined with topoisomerase I inhibitors may be an effective therapy against
      chemorefractory colorectal carcinoma tumors.

PMID- 12006512
TI  - Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony
      stimulating factor fusion protein (DT388GMCSF) for refractory or relapsed acute
      myeloid leukemia.
AB  - PURPOSE: Patients with relapsed or refractory acute myeloid leukemia have a poor
      prognosis. We tested the safety and efficacy of a diphtheria fusion protein
      [diphtheria toxin (DT)388 granulocyte-macrophage colony-stimulating factor
      (GMCSF)] directed against the GMCSF receptor that is strongly expressed by
      leukemic blasts. EXPERIMENTAL DESIGN: DT388GMCSF fusion protein containing the
      catalytic and translocation domains of DT388 fused to human GMCSF was
      administered in an interpatient dose escalation trial by 15 min i.v. infusion
      daily for up to 5 days. RESULTS: The maximal tolerated dose was 4 microg/kg/day.
      The dose-limiting toxicity was liver injury and occurred at the 4.5-5
      microg/kg/day dose level. Among nine treated patients at these doses, one patient
      developed liver failure, and one patient had transient hepatic encephalopathy.
      There was a positive correlation between peak serum DT388GMCSF levels and serum
      aspartate aminotransferase (P = 0.0002). DT388GMCSF did not damage hepatic cell
      lines in vitro; however, DT388GMCSF binds macrophages and induces cytokine
      release in vitro. Among the treated patients, we observed an early elevation in
      serum levels of interleukin (IL)-18 and a later rise in IL-8 but no significant
      changes in IL-1beta, IL-6, IFNgamma, macrophage inflammatory protein-1alpha,
      tumor necrosis factor alpha or IL-12. The IL-18 elevations occurred before
      elevations of liver enzymes and correlated with peak aspartate aminotransferase
      levels (P = 0.005). Of the 31 patients who were resistant to chemotherapy, 1 had
      a complete remission and 2 had partial remissions; all 3 of these patients were
      treated at or above the maximal tolerated dose, all 3 responding patients had
      baseline marrow blast percentage of <30%, whereas only 6 of the nonresponding 28
      patients had less than 30% marrow blasts. Five of these six patients were treated
      with subtherapeutic doses. Eight (42%) of 19 patient courses at <4 microg/kg/day
      and 8 (40%) of 20 patient courses at 4-5 microg/kg/day showed marrow blast
      reductions at day 12. Patients with higher pretreatment anti-DT388GMCSF levels
      had significantly lower peak DT388GMCSF levels (P = 0.0001). CONCLUSIONS:
      DT388GMCSF can produce complete and partial remissions in patients with
      chemotherapy-resistant acute myeloid leukemia, but methods to prevent liver
      injury are needed before more widespread application of this novel agent.

PMID- 12006513
TI  - Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377,
      results in short-lived peptide-specific immunity.
AB  - Ideally, vaccines should be designed to elicit long-lived immunity. The goal of
      this study was to determine whether HER-2/neu peptide-specific CD8+ T-cell
      immunity could be elicited using an immunodominant HER-2/neu-derived HLA-A2
      peptide alone in the absence of exogenous help. Granulocyte macrophage colony
      stimulating factor (GM-CSF) was used as adjuvant. Six HLA-A2 patients with HER
      2/neu-overexpressing cancers received 6 monthly vaccinations with a vaccine
      preparation consisting of 500 microg of HER-2/neu peptide, p369-377, admixed with
      100 microg of GM-CSF. The patients had either stage III or IV breast or ovarian
      cancer. Immune responses to the p369-377 were examined using an IFN-gamma enzyme
      linked immunosorbent spot assay. Before vaccination, the median precursor
      frequency (range), defined as precursors per 10(6) peripheral blood mononuclear
      cell, to p369-377 was 0 (no range). After vaccination, the median precursor
      frequency to p369-377 in four evaluable patients was 0 (0-116). Overall, HER
      2/neu peptide-specific precursors developed to p369-377 in two of four evaluable
      subjects. The responses were short-lived and not detectable at 5 months after the
      final vaccination. Immunocompetence was evident, because patients had detectable
      enzyme-linked immunosorbent spot responses to tetanus toxoid and influenza. These
      results demonstrate that HER-2/neu MHC class I epitopes can induce HER-2/neu
      peptide-specific IFN-gamma-producing CD8+ T cells. However, the magnitude of the
      responses were low, as well as short-lived, suggesting that CD4+ T-cell help is
      required for lasting immunity to this epitope.

PMID- 12006514
TI  - Induction of p53-specific immune responses in colorectal cancer patients
      receiving a recombinant ALVAC-p53 candidate vaccine.
AB  - PURPOSE: The tumor-associated auto-antigen p53 is commonly overexpressed in
      various types of human cancer, including colorectal cancer. Experiments in
      preclinical models have shown that it can serve as a target for T-cell-mediated
      tumor-eradication. The feasibility of a p53-specific therapeutic vaccination was
      investigated in cancer patients. EXPERIMENTAL DESIGN: A Phase I/II dose
      escalation study was performed that evaluated the effect of a recombinant
      canarypoxvirus (ALVAC) vaccine encoding wild-type human p53 in 15 patients with
      advanced colorectal cancer. Each group of five patients received three i.v. doses
      of one-tenth of a dose, one-third of a dose, or 1 dose of the vaccine [1 dose = 1
      x 10(7.5) cell culture infectious dosis (CCID)50]. RESULTS: Potent T-cell and IgG
      antibody responses against the vector component of the ALVAC vaccine were induced
      in the majority of the patients. Enzyme-linked immunosorbent-spot assay (ELISPOT)
      analysis of vaccine-induced immunity revealed the presence of IFN-gamma-secreting
      T cells against both ALVAC and p53, whereas no significant interleukin-4
      responses were detected. Vaccine-mediated enhancement of p53-specific T-cell
      immunity was found in two patients in the highest-vaccine-dose group.
      CONCLUSIONS: This study demonstrated the feasibility, even in patients with
      advanced cancer, to elicit immune responses against the ubiquitously expressed
      tumor-associated auto-antigen p53. Our results form the basis for additional
      studies that will explore the antitumor capacity of p53 containing multivalent
      vaccines in cancer patients with limited tumor burden.

PMID- 12006515
TI  - Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal
      dysplasia: a Phase I study of ZYC101.
AB  - High-grade dysplasia induced by high-risk types of human papillomavirus (HPV)
      precedes invasive cancer in anal squamous epithelium just as it does in the
      cervix. A therapeutic HPV vaccine strategy as a potential treatment for anal
      dysplasia was tested in a standard Phase I dose escalation trial. The primary
      objective was to evaluate the safety of the agent; additional study aims were to
      evaluate the histological response, immune response, and effect on anal HPV-16
      infection. Each subject was treated with four i.m. injections of 50-400 microg of
      ZYC101 at 3-week intervals. ZYC101 is composed of plasmid DNA encapsulated in
      biodegradable polymer microparticles. The plasmid DNA encodes for multiple HLA-A2
      restricted epitopes derived from the HPV-16 E7 protein, one of two HPV
      oncoproteins consistently expressed in neoplastic cells. Fifty-six potential anal
      dysplasia subjects were screened to identify 12 eligible subjects with HPV-16
      anal infection and a HLA-A2 haplotype. The investigational agent was well
      tolerated in all subjects at all dose levels tested. Three subjects experienced
      partial histological responses, including one of three subjects receiving the 200
      microg dose and two subjects at the 400-microg dose level. Using a direct
      Elispot, 10 of 12 subjects demonstrated increased immune response to the peptide
      epitopes encoded within ZYC101; each continued to show elevated immune responses
      6 months after the initiation of therapy. These results support the continued
      investigation of a therapeutic vaccination strategy for anal dysplasia.

PMID- 12006516
TI  - Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein
      stabilized, nanoparticle formulation of paclitaxel.
AB  - PURPOSE: ABI-007 is a novel Cremophor-free, protein-stabilized, nanoparticle
      formulation of paclitaxel. The absence of Cremophor EL may permit ABI-007 to be
      administered without the premedications used routinely for the prevention of
      hypersensitivity reactions. Furthermore, this novel formulation permits a higher
      paclitaxel concentration in solution and, thus, a decreased infusion volume and
      time. This Phase I study examines the toxicity profile, maximum tolerated dose
      (MTD), and pharmacokinetics of ABI-007. EXPERIMENTAL DESIGN: ABI-007 was
      administered in the outpatient setting, as a 30-min infusion without
      premedications. Doses of ABI-007 ranged from 135 (level 0) to 375 mg/m2 (level
      3). Sixteen patients participated in pharmacokinetic studies. RESULTS: Nineteen
      patients were treated. No acute hypersensitivity reactions were observed during
      the infusion period. Hematological toxicity was mild and not cumulative. Dose
      limiting toxicity, which occurred in 3 of 6 patients treated at level 3 (375
      mg/m2), consisted of sensory neuropathy (3 patients), stomatitis (2 patients),
      and superficial keratopathy (2 patients). The MTD was thus determined to be 300
      mg/m2 (level 2). Pharmacokinetic analyses revealed paclitaxel C(max) and area
      under the curve(inf) values to increase linearly over the ABI-007 dose range of
      135-300 mg/m2. C(max) and area under the curve(inf) values for individual
      patients correlated well with toxicity. CONCLUSIONS: ABI-007 offers several
      features of clinical interest, including rapid infusion rate, absence of
      requirement for premedication, and a high paclitaxel MTD. Our results provide
      support for Phase II trials to determine the antitumor activity of this drug.

PMID- 12006517
TI  - Impact of two weekly schedules of oral eniluracil given with fluorouracil and
      leucovorin on the duration of dihydropyrimidine dehydrogenase inhibition.
AB  - PURPOSE: This study determined the effect of different weekly dosing schedules of
      5-fluorouracil (5-FU)/leucovorin (LV)/eniluracil on dihydropyrimidine
      dehydrogenase (DPD) activity and plasma uracil levels. METHODS: Plasma and
      mononuclear cells were isolated from peripheral blood samples obtained before,
      during, and at various times after 5-FU/LV/eniluracil therapy. Two schedules were
      studied: 20 mg of eniluracil p.o. plus 30 mg of LV p.o. on days 1-3 with a single
      dose of 5-FU given day 2, or 30 mg of LV p.o. on days 1-2 with a single dose of
      eniluracil and 5-FU on day 2. DPD activity was determined with a radioisotopic
      enzyme assay; the reaction products were separated by high-performance liquid
      chromatography. Plasma uracil levels were determined by gas chromatography-mass
      spectroscopy. RESULTS: During oral therapy, DPD activity was profoundly
      depressed, and uracil levels were strikingly elevated with both schedules. With
      the daily-for-3-days schedule, DPD activity was similar to baseline values by 3
      weeks after the earlier eniluracil dose, whereas it appeared to recover earlier
      in patients receiving the single-dose schedule, reaching baseline values by 2
      weeks. Although baseline uracil values did not predict DPD activity accurately,
      plasma uracil levels >0.95 microM were associated with significantly lower DPD
      activity (median, 18.4 versus 287.6 pmol/min/mg). CONCLUSIONS: When eniluracil is
      given with 5-FU/LV, DPD inhibition appears to be influenced by schedule, and the
      time to recovery is much longer than has been observed with eniluracil given
      alone.

PMID- 12006518
TI  - Treatment of advanced breast cancer with docetaxel and gemcitabine with and
      without human granulocyte colony-stimulating factor.
AB  - PURPOSE: A multicenter Phase II trial was performed to investigate the efficacy
      and tolerance of combined docetaxel and gemcitabine +/- recombinant human
      granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast
      cancer. PATIENTS AND METHODS: Fifty-two patients participated in this trial, 51
      of whom are evaluable for response. Thirty-eight patients received this
      combination as first-line chemotherapy, and 14 patients received this combination
      as second-line chemotherapy, including 10 patients who had failed anthracyclines.
      Therapy consisted of 1500 mg/m2 gemcitabine and 50 mg/m2 docetaxel, both
      administered on days 1 and 15 every 4 weeks. Depending on the absolute neutrophil
      counts on the day of scheduled chemotherapeutic drug administration, a 5-day
      course of 5 microg/kg G-CSF was given. RESULTS: The overall response rate was
      60.5% (95% confidence interval, 43.4-75.9%) in patients receiving docetaxel plus
      gemcitabine as first-line chemotherapy, including 4 complete responses (10.5%)
      and 19 partial remissions (50%); 9 patients (24%) had disease stabilization, and
      only 5 (13%) progressed. Second-line treatment with this regimen resulted in 6 of
      14 (43%) objective responses, 5 had stable disease, and 3 progressive disease.
      The median time to progression was 8.5 months in the first-line setting and 6.6
      months in the second-line setting, respectively. After a median follow-up time of
      15 months, 36 patients (69%) are still alive with metastatic disease.
      Myelosuppression was commonly observed; WHO grade 3 or 4 neutropenia, however,
      occurred in only 15 (29%) patients and was complicated by septicemia in 2 cases;
      grade 3 anemia was seen in 1 patient (2%). Severe (grade 3) nonhematological
      toxicity except for alopecia was rarely observed and included nausea/vomiting in
      3 (6%), stomatitis in 2 (4%), anaphylaxis in 2, and peripheral neuropathy, skin
      toxicity, and increase of liver enzymes each in one patient. CONCLUSION: Our data
      suggest that docetaxel and gemcitabine with and without G-CSF is an effective and
      fairly well-tolerated regimen for the treatment of advanced breast cancer. It
      might be particularly useful in patients exposed previously to adjuvant or
      palliative anthracyclines and/or alkylating agents.

PMID- 12006519
TI  - A Phase I/pilot study of sequential doxorubicin/vinorelbine: effects on p53 and
      microtubule-associated protein 4.
AB  - PURPOSE: Few molecular determinants of sensitivity to cancer chemotherapy exist.
      In experimental systems, p53 regulates the sensitivity to antimicrotubule drugs
      through its effect on microtubule-associated protein 4 (MAP4). MAP4 is the major
      microtubule-associated protein in nonneuronal tissues and promotes microtubule
      polymerization. We reported that wild-type p53 induction by doxorubicin in C127
      breast cancer cells repressed MAP4, decreased microtubule polymerization, and
      increased Vinca alkaloid sensitivity. The goals of this Phase I/pilot clinical
      trial were to determine: (a) the safety of delivering a DNA-damaging agent
      (doxorubicin) followed in sequence by treatment with an antimicrotubule drug
      (vinorelbine); and (b) the feasibility of detecting activation of p53 and
      repression of MAP4 in patients' tissues. EXPERIMENTAL DESIGN: Peripheral blood
      mononuclear cells (PBMNCs) and tumor were obtained from 16 women with locally
      advanced (stage IIIb) or metastatic (stage IV) breast cancer before doxorubicin
      treatment and immediately before treatment with vinorelbine 24 or 48 h later.
      RESULTS: After doxorubicin treatment, p53 increased in 12 of 14 PBMNC and 4 of 10
      tumor samples. Changes in MAP4 were variable; however, in samples in which p53
      was induced, MAP4 decreased in 7 of 12 PBMNC and 3 of 4 breast cancer specimens.
      Immunohistochemistry confirmed lower MAP4 expression in tumor cells after
      doxorubicin treatment. Seven of 16 patients had a partial response, and treatment
      was well tolerated. CONCLUSIONS: These data demonstrate the ability to detect the
      activation of p53 and the repression of MAP4 in normal and malignant tissues in
      patients treated with a DNA-damaging agent, and that an antimicrotubule drug can
      be administered safely at a time when cells may be more sensitive to treatment.

PMID- 12006520
TI  - A Phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy
      for locally advanced lung and head and neck cancer.
AB  - PURPOSE: Preclinical data have demonstrated that farnesyltransferaseinhibitors
      (FTIs) are radiation sensitizers in selected cell lines. The objective of this
      Phase I trial was to determine the maximally tolerated dose of the FTI L-778,123
      in combination with radiotherapy in non-small cell lung cancer (NSCLC) and head
      and neck cancer (HNC). EXPERIMENTAL DESIGN: L-778,123 was given by continuous
      i.v. infusion and dose escalated in conjunction with standard radiotherapy. The
      presence of a ras mutation was not required for study entry. RESULTS: Nine
      patients (six NSCLC patients and three HNC patients) were enrolled on two dose
      levels of FTI. No dose-limiting toxicities were observed at the first dose level
      of 280 mg/m2/day during weeks 1, 2, 4, and 5 of radiotherapy. One episode of dose
      limiting toxicity, grade IV neutropenia, was observed in one of three patients
      treated at 560 mg/m2/day during weeks 1, 2, 4, 5, and 7. No episodes of dose
      limiting mucositis, esophagitis, or pneumonitis were observed. Of the four
      patients with NSCLC with evaluable disease, three patients had a complete
      response to treatment and one patient had a partial response. A complete clinical
      response to treatment was observed in two patients with HNC. In vitro studies in
      tumor cells obtained from a NSCLC patient on this trial showed radiosensitization
      with FTI and that tumor cells accumulated in G2-M after L-778,123 treatment.
      CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 is
      associated with acceptable toxicity. Local responses have been observed in four
      NSCLC patients without a clear increase in radiotherapy-associated toxicities.

PMID- 12006521
TI  - Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable
      breast cancer: preliminary data of a prospective randomized trial.
AB  - PURPOSE: Paclitaxel has significant antitumor activity in patients with
      metastaticbreast cancer who have been previously treated with or exposed to
      anthracycline-containing chemotherapy. In this prospective randomized trial, the
      role of paclitaxel was evaluated in an adjuvant setting to determine its impact
      on reducing the risk of recurrence in patients with operable breast cancer.
      EXPERIMENTAL DESIGN: Five hundred twenty-four patients were randomized to be
      treated either with 4 cycles of paclitaxel followed by 4 cycles of combination
      therapy with 5-fluorouracil, Adriamycin, and cyclophosphamide (Pac/FAC) or with 8
      cycles of FAC alone. Patients with intact primary breast cancer received the
      initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting.
      Planned duration of therapy was the same in all patients. After completion of 8
      cycles of chemotherapy, those patients who were > or =50 years and whose tumors
      were positive for estrogen receptors received tamoxifen for 5 years. RESULTS:
      Ninety-two patients have had a recurrence after a median follow-up of 60 months
      with a range of 5-89 months. Estimated disease-free survival at 48 months was
      0.83 for FAC and 0.86 for Pac/FAC group. The difference between the two groups
      was not statistically significant (P = 0.09). The overall estimated hazard ratio
      for Pac/FAC compared with FAC derived by fitting the Cox regression model and
      incorporating terms for prognostic factors was 0.66. CONCLUSION: Preliminary
      results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or
      neoadjuvant therapy may further reduce the risk of disease recurrence; however,
      differences were not statistically significant. At the time of this analysis,
      there have been 47 deaths. The survival data are too preliminary to permit
      meaningful evaluation of the impact of paclitaxel on mortality.

PMID- 12006523
TI  - Detection of circulating cytokeratin-positive cells in the blood of breast cancer
      patients using immunomagnetic enrichment and digital microscopy.
AB  - PURPOSE: To examine the feasibility for identifying and enumerating cytokeratin
      positive (CK+) cells in the peripheral blood of breast cancer patients.
      EXPERIMENTAL DESIGN: Blood specimens from 34 normal donors (negative controls),
      15 samples to which carcinoma cells were added (positive controls), and 84 breast
      cancer patients [27 node-negative (N-), 29 node-positive (N+), and 28 metastatic]
      were studied. RBCs were lysed with ammonium chloride and the resulting cell
      suspension incubated with anti-EpCAM-conjugated immunomagnetic beads for
      carcinoma cell enrichment. Immunomagnetically selected cells were placed on
      slides; stained for CKs 8, 18, and 19; and evaluated with an automated digital
      microscopy system that rapidly scanned the slide and collected images of cells
      meeting predefined staining and cytomorphological criteria. A montage of the CK+
      cells was reviewed to confirm tumor cell morphology. RESULTS: Eighteen specimens
      (9 normal, 2 N-, 4 N+, and 3 metastatic) were excluded because of poor
      cytomorphology or staining artifact. All 15 of the positive controls [95%
      confidence interval (CI), 78-100%] and none of the 25 negative controls (95% CI,
      0-14%) demonstrated CK+ cells. Twenty-one of the 75 (28%; 95% CI, 18-40%) samples
      from breast cancer patients demonstrated CK+ cells including 76% of patients with
      metastatic disease (95% CI, 55-91%), 8% with N+ disease (95% CI, 1-26%), and none
      of those with N- disease (95% CI, 0-14). The mean number of CK+ cells detected in
      the 21 CK+ patients was 18.4 (range, 1-120). CONCLUSIONS: Breast carcinoma cells
      can be detected in the blood from a significant fraction of metastatic breast
      cancer patients using immunomagnetic cell enrichment and digital microscopy. The
      incidence of CK+ cells was low in those with resected N+ disease (at most 26%)
      and those with resected N- breast cancer (at most 14%). This technique could be
      used in large prospective studies of patients with breast cancer to learn whether
      the detection of rare carcinoma cells is a useful predictive or prognostic
      factor.

PMID- 12006522
TI  - Pamidronate induces modifications of circulating angiogenetic factors in cancer
      patients.
AB  - PURPOSE: Recently, new experimental data suggested that, besides inhibiting
      osteoclasts, bisphosphonate may also have an antitumor effect. Antiangionetetic
      activity is one of the possible mechanisms of anticancer activity attributed to
      bisphosphonates. The purpose of this study was to evaluate the modifications in
      angiogenic cytokines levels after pamidronate infusion. EXPERIMENTAL DESIGN:
      Twenty-five consecutive cancer patients with bone metastases treated monthly with
      disodium pamidronate infusion were evaluated prospectively for circulating levels
      of vascular endothelial growth factor (VEGF), gamma-IFN, interleukin (IL)-6, and
      IL-8 at different time points: just before and after 1, 2, and 7 days after
      pamidronate infusion. RESULTS: Basal VEGF levels decreased significantly 1, 2,
      and 7 days after pamidronate infusion. gamma-IFN and IL-6 levels increased 1 day
      after the infusion but rapidly decreased after 2 days. Moreover, our data showed
      a statistically significant negative correlation between VEGF and gamma-IFN
      levels (P < 0.0001) and a positive correlation between VEGF and IL-8 (P = 0.04).
      CONCLUSIONS: This study confirms that pamidronate could have antiangiogenic
      properties through a significant and lasting decrease of VEGF serum levels.

PMID- 12006524
TI  - Intestinal trefoil factor: a marker of poor prognosis in gastric carcinoma.
AB  - PURPOSE: Intestinal trefoil factor (ITF) is a marker of intestinal
      differentiation that may also play a role in cancer cell biology by inhibiting
      cell adhesion, promoting cell invasion, and blocking apoptosis. Gastric
      adenocarcinomas can arise through a process of intestinalization, but no study
      has yet comprehensively examined the expression of ITF in gastric cancer or
      correlated ITF expression with clinical outcome in any cancer type. EXPERIMENTAL
      DESIGN: Patients (209) with primary gastric adenocarcinoma were evaluated for ITF
      expression by immunohistochemistry. Results of immunostaining were correlated
      with clinicopathological variables and overall survival. RESULTS: In normal
      gastric mucosa, ITF expression was absent, whereas areas of intestinal metaplasia
      revealed strong ITF expression by goblet cells. A portion of gastric cancers
      (55%) demonstrated ITF expression. Women were more likely than men to express ITF
      in gastric cancers. However, in men, the expression of ITF correlated with
      aggressive phenotype of tumors (advanced stage, infiltrative growth pattern, and
      positive lymph nodes). Multivariate analysis revealed that expression of ITF was
      associated with a poor prognosis, independent of tumor stage. CONCLUSIONS: This
      is the first study to correlate ITF expression with clinicopathological features
      or outcome in any cancer type. ITF expression in gastric cancer exhibited a
      curious gender-associated relationship, being more frequently expressed in tumors
      of women, but associated with more aggressive pathological features in men. The
      poor prognosis of patients with ITF-positive gastric cancers further implicates
      ITF in cancer cell biology.

PMID- 12006525
TI  - Dysregulation of PTEN and protein kinase B is associated with glioma histology
      and patient survival.
AB  - PURPOSE: This study assessed whether putative effectors of phosphatidylinositol3
      kinase, including PTEN, protein kinase B (PKB), and p27(kip1), correlate with
      each other, with glioma histology, and with patient outcome. EXPERIMENTAL DESIGN:
      Components of the phosphatidylinositol 3-kinase signaling cascade were
      characterized in 25 glioblastoma multiforme (GBM) tumors, 8 grade II
      oligoastrocytomas, and 13 normal human brain specimens. The protein levels of
      PTEN and p27(kip1) were assessed by immunoblot analyses. PKB kinase activity was
      evaluated through the expression level of the phosphorylated (activated) PKB
      protein and the ability of PKB to phosphorylate a specific peptide substrate in
      vitro. Cox regression analyses between expression/activity variables and survival
      were performed across and within histology types. Actual value for
      expression/activity was used as a continuous variable. Survival time was
      displayed by Kaplan Meier. RESULTS: A strong inverse correlation was evident
      between PTEN levels and both phosphorylated PKB expression (P < 0.01) and PKB
      activity (P = 0.01). p27(kip1) levels did not correlate with PTEN expression or
      PKB activity. A significant association was evident between PTEN expression level
      and histology (P < 0.01). PTEN levels were highest in normal brain, lowest in GBM
      tumors, and intermediate in grade II oligoastrocytomas. PKB activity and
      phosphorylated PKB levels differed significantly among histologies, whereas
      p27(kip1) levels exhibited no association with histology. PTEN expression
      correlated significantly with survival time within the entire cohort (P < 0.01)
      and was associated with survival within the subgroup of GBM tumors (P = 0.11).
      CONCLUSIONS: Reduced PTEN expression is ubiquitous among GBM tumors and may play
      a role in the development of low-grade gliomas. PTEN inactivation in gliomas
      portends a particularly aggressive clinical behavior.

PMID- 12006526
TI  - HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive
      markers in node-positive breast cancer patients randomly treated either with an
      anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5
      fluorouracil.
AB  - PURPOSE: The purpose of this study is to evaluate HER-2 and topoisomerase IIalpha
      (topo IIalpha) as candidates for predicting the activity of anthracyclines in the
      adjuvant treatment of breast cancer patients. EXPERIMENTAL DESIGN: In this study,
      we evaluated HER-2 and topo IIalpha gene aberrations by fluorescence in situ
      hybridization in a series of 430 primary breast cancer samples. Samples came from
      node-positive breast cancer patients randomly treated either with one of two
      anthracycline-based regimens [full-dose epirubicin-cyclophosphamide (HEC) and
      moderate-dose epirubicin-cyclophosphamide (EC)] or with cyclophosphamide,
      methotrexate, and 5-fluorouracil (CMF) in the context of a Phase III adjuvant
      therapy trial. Event-free survival comparisons were performed between the three
      study arms in the subgroups of HER-2-amplified and nonamplified tumors. An
      explorative analysis was also performed to evaluate the predictive value of topo
      IIalpha in the cohort of HER-2-amplified patients. RESULTS: HER-2 amplification
      was observed in 73 of the 354 evaluable samples (21%), whereas topo IIalpha
      amplification was found in 23 of the 61 evaluable HER-2-amplified tumors (38%).
      The three event-free survival comparisons were CMF versus HEC, CMF versus EC, and
      EC versus HEC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were as
      follows: (a) CMF versus HEC, HR = 1.42 for HER-2-amplified tumors (95% CI, 0.54
      3.76; P = 0.48) and 0.84 for HER-2-nonamplified tumors (95% CI, 0.49-1.44; P =
      0.53); (b) CMF versus EC, HR = 1.65 for HER-2-amplified tumors (95% CI, 0.66
      4.13; P = 0.29) and 0.66 for HER-2-nonamplified tumors (95% CI, 0.39-1.10; P =
      0.11); and (c) EC versus HEC, HR = 0.93 for HER-2-amplified tumors (95% CI, 0.31
      2.77, P = 0.90) and 1.33 for HER-2-nonamplified tumors (95% CI, 0.82-2.14; P =
      0.25). Observed HRs suggest that the anthracycline-based therapy could be more
      effective than CMF in the subgroup of HER-2-amplified patients, whereas
      treatments could be equally active in the HER-2-nonamplified cohort. topo IIalpha
      evaluation suggests that the superiority of anthracyclines over CMF in HER-2
      amplified patients could be confined to the subgroup of topo IIalpha-amplified
      tumors. CONCLUSIONS: HER-2 could have a predictive value for the activity of
      anthracycline-based regimens in the adjuvant therapy of breast cancer patients.
      The predictive value of HER-2 would most likely be related to the concomitant
      amplification of the topo IIalpha gene.

PMID- 12006527
TI  - Prognostic impact of TP53 mutations and P53 protein overexpression in
      supratentorial WHO grade II astrocytomas and oligoastrocytomas.
AB  - PURPOSE: The purpose of this study was to analyze retrospectively timing,
      frequency, and prognostic impact of TP53 mutations and P53 protein accumulation
      in supratentorial WHO grade II astrocytomas and oligoastrocytomas of adult
      patients. EXPERIMENTAL DESIGN: We included 159 consecutively treated patients
      (1991-1998), and each tumor was screened for TP53 mutations and P53 protein
      overexpression. Prognostic evaluation was performed with the multivariate
      proportional hazards model. RESULTS: TP53 mutations (P53 protein overexpression)
      were detected in 49% (47%) of all tumors with a preference for the gemistocytic
      subtype (P < 0.05). The TP53 status of the primary tumor was predictive for the
      status of the recurrent tumor, and tumor recurrence/progression was associated
      with an increase of P53 immunopositive cells in 68% of the investigated tumors.
      Univariately, gemistocytic subtype and presence of TP53 mutation (but not P53
      accumulation) were unfavorable predictors for progression-free survival (P <
      0.05); multivariately, only the gemistocytic subtype remained unfavorable
      influence (P = 0.04). No overall prognostic impact of the TP53 status on survival
      and time to malignancy was observed (P < 0.05). Five nongemistocytic tumors with
      a codon 175 TP53 mutation exhibited a significantly worse prognosis as compared
      with those with any other mutational sites (5-year progression-free survival: 0%;
      5-year malignant transformation: 100%; P < 0.001). CONCLUSIONS: TP53 mutations
      are frequent and early events in the pathogenesis of WHO grade II
      astrocytomas/oligoastrocytomas, and most of the univariately detected overall
      prognostic impact of the TP53 status must be related to the influence of the
      gemistocytic subtype. In nongemistocytic astrocytomas, a hot spot codon 175 TP53
      mutation indicates a worse prognosis in terms of time to progression and
      malignancy.

PMID- 12006528
TI  - Inhibition of infiltration and angiogenesis by thrombospondin-1 in papillary
      thyroid carcinoma.
AB  - PURPOSE: Angiogenesis is essential for tumor growth and is controlled by the
      balance between angiogenic and antiangiogenic factors. We studied the expression
      of angiogenic factors and antiangiogenic factors in papillary thyroid carcinoma.
      EXPERIMENTAL DESIGN: We investigated immunohistochemically the expression
      patterns and levels of antiangiogenic factor and its receptor, thrombospondin-1
      (TSP-1) and CD36, and four angiogenic factors, vascular endothelial growth factor
      (VEGF), VEGF-C, angiopoietin-2 (Ang-2), and Tie-2, in the primary tumors of 75
      papillary thyroid carcinoma patients. We also examined the microvessel count
      (MVC), using CD31 staining. RESULTS: VEGF expression strongly correlated with
      other angiogenic factors. The cytoplasm of cancer cells stained positive for all
      factors. Tie-2 and TSP-1 receptor also appeared in endothelia of microvessels.
      TSP-1 inversely correlated with the degree of invasion of the primary tumor to
      other adjacent organs and with MVC. A higher MVC correlated with poorer survival.
      To clarify the balance between angiogenic and antiangiogenic factors in the same
      tumor, we calculated the ratio of each angiogenic factor against TSP-1 as the
      antiangiogenic factor. The ratios VEGF/TSP-1, VEGF-C/TSP-1, and Ang-2/TSP-1
      significantly correlated with a higher MVC. Furthermore, the ratios VEGF/TSP-1
      and Ang-2/TSP-1 significantly correlated with the degree of infiltration.
      CONCLUSIONS: To the best of our knowledge, this is the first report demonstrating
      that the balance between angiogenic and antiangiogenic factors correlates with
      distinct invasion to other organs and neovascularization of papillary thyroid
      carcinoma.

PMID- 12006529
TI  - Prognostic significance of soluble urokinase plasminogen activator receptor in
      serum and cytosol of tumor tissue from patients with primary breast cancer.
AB  - PURPOSE: The aim of the study was to evaluate the prognostic value of soluble
      urokinase plasminogen activator receptor (suPAR) in preoperatively obtained sera
      samples (s-suPAR) from breast cancer patients. EXPERIMENTAL DESIGN: suPAR levels
      were determined by the use of a kinetic ELISA in sera from 274 breast cancer
      patients and in tumor cytosols (c-suPAR) from 188 of these patients. In addition,
      s-suPAR levels were analyzed in 174 female blood donors. RESULTS: The mean s
      suPAR level was 3.8 ng/ml (range, 1.6-9.2 ng/ml) in the patients and 3 ng/ml
      (range, 1.3-6.4 ng/ml) in the donors. The mean c-suPAR level was 0.55 ng/mg
      protein (range, 0.07-2.83 ng/mg protein). A weak but significant linear
      association was found between s-suPAR and age in the donors; thus, all of the s
      suPAR levels were adjusted for this age dependency (aa-s-suPAR). The aa-s-suPAR
      levels were significantly increased in the patients as compared with the donors
      (P < 0.0001). No difference was found in aa-s-suPAR levels between the lymph node
      positive and -negative patients (P = 0.27), and no correlation was seen between
      aa-s-suPAR and c-suPAR (sigma = 0.08; P = 0.71). During the follow-up period (5.9
      years) 77 patients experienced a relapse and 69 died. aa-s-suPAR as a continuous
      variable was significantly associated with relapse-free survival [hazard ratio
      (HR), 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.003] and overall survival
      (HR, 1.6; 95% CI, 1.2-2.0; P < 0.0001). In multivariate Cox analysis including
      the classical prognostic parameters in breast cancer, continuous aa-s-suPAR was
      significantly associated with both relapse-free survival (HR, 1.4; 95% CI, 1.1
      1.7; P = 0.001) and overall survival (HR, 1.4; 95% CI, 1.1-1.8; P = 0.002). In
      these analyses positive lymph nodes, tumor size >2 cm, and negative estrogen
      receptor content were also significantly associated with patient outcome.
      CONCLUSION: This study shows that high preoperative aa-s-suPAR levels are
      significantly associated with poor outcome for breast cancer patients independent
      of lymph node status, tumor size, and estrogen receptor status.

PMID- 12006530
TI  - Doppler ultrasonography of the uterine artery and the response to chemotherapy in
      patients with gestational trophoblastic tumors.
AB  - PURPOSE: Increasing new blood vessel formation (neoangiogenesis) within tumors is
      an adverse prognostic factor for survival in several cancers. Neoangiogenesis is
      usually determined histopathologically and not in vivo. To assess neoangiogenesis
      in vivo, we have used Doppler ultrasonography (US) to measure the uterine artery
      pulsatility index (UAPI) in patients with gestational trophoblastic tumors
      (GTTs). Here, we assess whether the UAPI can provide independent prognostic
      information predictive of methotrexate resistance (MTX-R), a drug central to the
      management of GTT. EXPERIMENTAL DESIGN: All patients treated for GTTs between
      March 1994 and January 1999 had their records reviewed to determine their
      pretreatment Charing Cross Hospital (CXH) prognostic score, uterine volume, the
      lowest UAPI of either uterine artery, number of metastases, and human chorionic
      gonadotropin (hCG) concentration. Of the 164 patients for whom all data were
      available, 47 subsequently developed MTX-R, defined as a plateaued or rising hCG
      in two consecutive samples. RESULTS: UAPI, hCG, uterine volume, presence of
      metastases, and the overall CXH prognostic score were all predictive of MTX-R on
      univariate analysis. Moreover, the UAPI remained a significant independent
      predictor of MTX-R on multiple logistic regression analysis. After adjustment for
      the CXH prognostic score, the odds ratio for the risk of MTX-R in patients with a
      UAPI < or =1 compared with those with a UAPI >1 was 2.68 (95% confidence
      interval, 1.25-5.74; P = 0.01). The unadjusted odds ratio for the above
      comparison was 2.32 (95% confidence interval, 1.14-4.7; P = 0.02). CONCLUSIONS:
      The UAPI, as an indirect in vivo measure of functional tumor vascularity,
      independently predicts the response to chemotherapy in GTTs.

PMID- 12006531
TI  - Ki-67 staining is an independent correlate of biochemical failure in prostate
      cancer treated with radiotherapy.
AB  - PURPOSE: To determine the significance of Ki-67/MIB1 staining as a marker of
      patient outcome for prostate cancer patients treated with radiotherapy.
      EXPERIMENTAL DESIGN: Pretreatment archival prostate biopsy tumor tissue was
      available from 106 stage T1-T4 prostate cancer patients treated with external
      beam radiotherapy between 1987 and 1993 at M. D. Anderson Cancer Center.
      Diagnosis was made from prostate needle biopsy in 64 cases and from transurethral
      resection of the prostate (TURP) in 42 cases. All patients had a pretreatment
      prostate-specific antigen (PSA), and no patient had evidence of metastasis.
      Immunohistochemical staining for MIB1 was used to determine the percentage of Ki
      67-positive tumor cells, the Ki-67 labeling index (Ki67-LI). Biochemical failure
      after radiotherapy was defined as three rises in PSA on follow-up. Median follow
      up was 62 months. RESULTS: The mean and median Ki67-LI for the entire cohort was
      3.2 and 2.3. The mean and median Ki67-LIs for those diagnosed by needle biopsy
      were 3.2 and 2.3, and by TURP were 3.1 and 2.4. For all patients, mean Ki67-LI
      levels were significantly higher with stage T3/T4 disease, Gleason 7-10 disease,
      and in those that developed treatment failure. Similar relationships were
      observed when the Ki67-LI was dichotomized into low (< or =3.5%) and high (>3.5%)
      groups. Actuarial freedom from biochemical failure (bNED) when Ki67-LI was low
      and high was 76 and 33% at 5 years (P < 0.0001, log rank). Similar statistically
      significant differences were observed when the TURP and needle biopsy groups were
      analyzed separately. Cox proportional hazards regression showed that dichotomized
      Ki67-LI was an independent correlate of bNED, along with pretreatment PSA,
      Gleason score, and clinical stage. CONCLUSIONS: The Ki67-LI obtained from
      pretreatment prostate cancer tissue is a strong independent predictor of failure
      after radiotherapy using biochemical criteria. This prognostic factor was equally
      valuable for patients diagnosed by TURP or needle biopsy.

PMID- 12006532
TI  - Development and validation of a method for using breast core needle biopsies for
      gene expression microarray analyses.
AB  - PURPOSE: Gene expression microarray technologies have the potential to define
      molecular profiles that may identify specific phenotypes(diagnosis), establish a
      patient's expected clinical outcome (prognosis), and indicate the likelihood of a
      beneficial effect of a specific therapy (prediction). We wished to develop
      optimal tissue acquisition, processing, and analysis procedures for exploring the
      gene expression profiles of breast core needle biopsies representing cancer and
      noncancer tissues. EXPERIMENTAL DESIGN: Human breast cancer xenografts were used
      to evaluate several processing methods for prospectively collecting adequate
      amounts of high-quality RNA for gene expression microarray studies. Samples were
      assessed for the preservation of tissue architecture and the quality and quantity
      of RNA recovered. An optimized protocol was applied to a small study of core
      needle breast biopsies from patients, in which we compared the molecular profiles
      from cancer with those from noncancer biopsies. Gene expression data were
      obtained using Research Genetics, Inc. Named Genes cDNA microarrays. Data were
      visualized using simple hierarchical clustering and a novel principal component
      analysis-based multidimensional scaling. Data dimensionality was reduced by
      simple statistical approaches. Predictive neural networks were built using a
      multilayer perceptron and evaluated in an independent data set from snap-frozen
      mastectomy specimens. RESULTS: Processing tissue through RNALater preserves
      tissue architecture when biopsies are washed for 5 min on ice with ice-cold PBS
      before histopathological analysis. Cell margins are clear, tissue folding and
      fragmentation are not observed, and integrity of the cores is maintained,
      allowing optimal pathological interpretation and preservation of important
      diagnostic information. Adequate concentrations of high-quality RNA are
      recovered; 51 of 55 biopsies produced a median of 1.34 microg of total RNA
      (range, 100 ng to 12.60 microg). Snap-freezing or the use of RNALater does not
      affect RNA recovery or the molecular profiles obtained from biopsies. The neural
      network predictors accurately discriminate between predominantly cancer and
      noncancer breast biopsies. CONCLUSIONS: The approaches generated in these studies
      provide a simple, safe, and effective method for prospectively acquiring and
      processing breast core needle biopsies for gene expression studies. Gene
      expression data from these studies can be used to build accurate predictive
      models that separate different molecular profiles. The data establish the use and
      effectiveness of these approaches for future prospective studies.

PMID- 12006533
TI  - High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast
      cancer patients.
AB  - PURPOSE: The prognostic significance of the Wilms' tumor suppressor gene(WT1)
      mRNA expression was evaluated in patients with invasive breast cancer.
      EXPERIMENTAL DESIGN: WT1 mRNA expression in tumor tissues (n = 99) was examined
      by a quantitative, real-time PCR assay. RESULTS: No significant association was
      observed between WT1 mRNA levels and clinicopathological parameters such as
      menopausal status, tumor size, lymph node status, histological grade, and
      estrogen receptor status. Five-year disease-free survival rate of patients with
      high WT1 mRNA levels (62.6%) was significantly (P < 0.05) poorer than those with
      low WT1 mRNA levels (77.2%). Lymph node metastasis (P < 0.05), high histological
      grade (P < 0.01), and estrogen receptor negativity (P < 0.05) were also
      significantly associated with poor prognosis, respectively. Multivariate analysis
      revealed that WT1 mRNA levels were a significant prognostic factor, independent
      of the other conventional prognostic factors. CONCLUSIONS: These results suggest
      that measurement of WT1 mRNA levels in tumor tissues might be useful as a new
      prognostic factor in breast cancer patients.

PMID- 12006534
TI  - Maspin expression profile in human prostate cancer (CaP) and in vitro induction
      of Maspin expression by androgen ablation.
AB  - PURPOSE: Expression of tumor suppressor gene, MASPIN, is associated with
      inhibition of tumor cell invasion and metastasis. Loss of or decreased expression
      of Maspin is found frequently in breast and prostate cancer cells. The objective
      of this study is to investigate Maspin expression in prostate tumor specimens and
      explore the mechanisms of hormonal regulation of Maspin expression in prostate
      tumors. EXPERIMENTAL DESIGN: Immunohistochemical staining of Maspin expression
      was performed on surgical whole-mounted prostate specimens. The expression of
      Maspin was scored on individual tumors. Correlation of Maspin expression with
      clinicopathological features was analyzed for statistical significance. Androgen
      ablation-induced Maspin expression was analyzed by Maspin promoter luciferase
      reporter assay and quantitative reverse transcription-PCR analysis of endogenous
      Maspin expression in LNCaP cells in vitro and in animal model. RESULTS:
      Comprehensive evaluation of Maspin expression profile in multiple tumor foci from
      whole mounted prostate specimens of prostate cancer patients revealed absence of
      Maspin expression in a significant fraction (63%). However, Maspin expression is
      significantly higher in tumor specimens (92%) of patients treated with
      neoadjuvant androgen ablation therapy before radical prostatectomy. LNCaP cells
      cultured in androgen-depleted medium show induction of Maspin promoter activity
      in a promoter luciferase reporter assay. In addition, Maspin expression is
      increased after castration in LNCaP prostate cancer cells derived tumors in nude
      mice. CONCLUSIONS: Maspin expression is frequently absent in primary prostate
      cancers. Up-regulation of MASPIN in response to androgen ablation strongly
      suggests a physiological role of Maspin in growth inhibition and/or apoptosis of
      prostate cancer cells during androgen ablation.

PMID- 12006535
TI  - Lack of PTEN expression in non-small cell lung cancer could be related to
      promoter methylation.
AB  - PURPOSE: The PTEN gene at chromosome 10q23.3 is a tumor-suppressor genethat is
      inactivated in several types of human tumors. Althoughmutation and homozygous
      deletion are the most commonmechanisms of PTEN inactivation, promoter methylation
      and translational modification can also account for PTEN silencing. The aim of
      this study was to investigate the expression of PTEN protein in primary non-small
      cell lung cancer (NSCLC) samples and to investigate the promoter methylation
      status of the gene in a panel of NSCLC cell lines as well as primary tumors.
      EXPERIMENTAL DESIGN: We analyzed PTEN expression by immunohistochemistry in
      tissue samples from 125 patients with early-stage NSCLC. We also evaluated PTEN
      promoter methylation status by methylation-specific PCR in 20 microdissected PTEN
      negative primary tumors from among the last specimens as well as in a panel of 16
      NSCLC cell lines. Western and Northern blotting were performed in the same panel
      of NSCLC cell lines. RESULTS: Thirty (24%) of the 125 specimens showed a lack of
      staining for PTEN. PTEN methylation was detected in 7 (35%) of the 20 PTEN
      negative NSCLC samples and in none of the 10 PTEN-positive NSCLC samples that
      were microdissected. Furthermore, PTEN methylation was observed in 11 (69%) of
      the 16 NSCLC cell lines tested. PTEN mRNA expression was increased in the NCI
      H1299 cell line by in vitro treatment with the demethylating agent 5-aza-2'
      deoxycytidine. PTEN methylation was well correlated with PTEN expression in NSCLC
      cell lines by Western and Northern blot (P = 0.025). CONCLUSIONS: Although
      genetic alterations of the PTEN gene are rare in NSCLC, loss of PTEN protein is
      not an uncommon event in early-stage NSCLC. Lack of PTEN expression may be
      partially explained by promoter methylation.

PMID- 12006536
TI  - Differential assessment of vascular survival ability and tumor angiogenic
      activity in colorectal cancer.
AB  - BACKGROUND: The process of new vessel formation during neoplastic transformation
      and growth (neoangiogenesis) comprises proliferation, sprouting, and migration of
      endothelial cells within normal tissues adjacent to the tumor. These new vessels
      are directed toward the tumor invading edge and provide the bed for the
      subsequent growth of new tumor layers. We previously showed various degrees of
      decreasing vascular density in tumor layers once these lose contact with the
      normal tissue. This suggests that, apart from angiogenic factors, vascular
      survival factors contribute equally to the structure of the tumoral vasculature.
      This "vascular survival" potential can be assessed by comparatively examining the
      vascular density in peripheral and inner tumor areas. EXPERIMENTAL DESIGN: Using
      immunohistochemistry with the anti-CD31 monoclonal antibody, we assessed the
      tumor angiogenic activity (TAA) and vascular survival ability (VSA) in a sample
      of 242 patients with Dukes' stage A (90 patients), B (73 patients), and C (79
      patients) colorectal cancer treated with surgery alone. RESULTS: Overall, High
      TAA and VSA were significantly related with poor prognosis (P = 0.03; hazard
      ratio, 1.9 and P = 0.001; hazard ratio, 2.7, respectively). In multivariate
      analysis, VSA was revealed as the most potent and independent prognostic factor
      (P = 0.0001; t ratio, 4.5), followed by vascular invasion (P = 0.0001; t ratio,
      4.4) and stage (P = 0.01; t ratio, 2.5). Tumors with high TAA and high VSA had a
      significantly higher risk to develop liver metastasis (P = 0.0003). CONCLUSIONS:
      Assessment of VSA in addition to TAA provides additional important prognostic
      information in patients with colorectal cancer and can be a useful tool in the
      recruitment of patients who would benefit from angiostatic versus angiotoxic
      therapies.

PMID- 12006537
TI  - p53 mutation arising in Arg72 allele in the tumorigenesis and development of
      carcinoma of the urinary tract.
AB  - PURPOSE: It is known that a common p53 polymorphism, encodingeither proline (Pro)
      or arginine (Arg) at residue 72, produces marked change in the structure of p53.
      Furthermore, the Arg72-containing allele is preferentially mutated and retained
      in various human tumors, suggesting that polymorphic residue within p53 modifies
      mutant behavior. We studied to determine whether Arg72 could be a risk factor for
      p53 mutations in human transitional cell carcinomas (TCCs). In addition, the
      relationship between the status of p53 codon 72 polymorphism and
      clinicopathological factors of this tumor were also analyzed. EXPERIMENTAL
      DESIGN: We analyzed the correlation between the p53 mutations and genotypes of
      its codon 72 using genomic DNAs from the TCCs by direct DNA sequencing. Loss of
      heterozygosity was determined using a p53 microsatellite marker (TP53) amplified
      by PCR. RESULTS: There was a bias to mutate and express the Arg allele in the p53
      -mutated TCCs arising in individuals with heterozygosity (Pro/Arg). The Arg72
      containing allele was preferentially retained in these tumors. The prevalence of
      cases with p53 mutations within Arg72-containing allele was higher for advanced
      stage TCCs (chi(2) = 5.320, P = 0.021) than for TCCs with those arising in Pro72
      containing allele. CONCLUSIONS: Our in vivo findings suggested that p53 mutation
      alleles containing Arg72 are preferentially selected during tumorigenesis and
      affect mutant behavior in TCCs, and revealed that TCCs with p53 mutation arising
      in Arg72-containing allele became progressively more abundant with increase in
      tumor stage.

PMID- 12006538
TI  - Failure of BRCA1 dysfunction to alter ovarian cancer survival.
AB  - PURPOSE: Many factors modify ovarian cancer survival. There are conflicting
      reports regarding survival of individuals with hereditary BRCA1-related ovarian
      cancer. None have controlled for other mechanisms of BRCA1 silencing in the
      control cohort. EXPERIMENTAL DESIGN: Fifty-nine cancers with presumed BRCA1
      dysfunction because of mutation (24 germ-line and 16 somatic) or absent BRCA1
      mRNA because of promoter hypermethylation (n = 19) were identified among 250
      consecutively screened ovarian cancers. Controls were matched from the same
      population based on p53 mutation type, age at diagnosis, Federation
      Internationale des Gynaecologistes et Obstetristes surgical stage and
      histological grade, residual disease, preoperative CA125, disease site, and the
      presence of BRCA1 mRNA translatable in an in vitro protein expression assay.
      BRCA1 promoter hypermethylation was determined by the methylation-specific PCR
      technique. The significance of promoter hypermethylation was confirmed by the
      absence of detectable BRCA1 mRNA. RESULTS: The median survival for individuals
      with ovarian cancer BRCA1 dysfunction was 4.1 years versus 3.5 years in the case
      matched controls (P = 0.98). Grouped on the basis of the mechanism of BRCA1
      dysfunction, median survival was 4.5, 2.8, and 2.3 years for germ-line, somatic,
      and BRCA1 promoter-silenced ovarian cancers. However, for the corresponding
      matched controls with wild-type BRCA1 sequence, the median survival was virtually
      identical: 4.6, 2.8, and 3.3 years, respectively. In a Cox proportional hazards
      analysis, only residual disease (P = 0.0001), age (P = 0.01), and Federation
      Internationale des Gynaecologistes et Obstetristes stage (P = 0.011) entered the
      survival model. CONCLUSIONS: In contrast with other published reports, we are
      unable to detect large survival differences between matched case-control cohorts
      of ovarian cancers with BRCA1 inactivation by any of three independent
      mechanisms.

PMID- 12006539
TI  - Real-time quantitative PCR demonstrates low prevalence of human papillomavirus
      type 16 in premalignant and malignant lesions of the oral cavity.
AB  - PURPOSE: Human papillomavirus (HPV) type-16 has been associated with invasive
      squamous cell carcinoma of the head and neck. This study examines the role of HPV
      16 in the progression of oral head and neck cancer by determining the quantity of
      HPV-16 DNA in premalignant and malignant lesions, using real-time quantitative
      PCR, to more accurately determine the role of HPV-16 in oral head and neck
      squamous cell carcinogenesis. EXPERIMENTAL DESIGN: We examined 102 microdissected
      premalignant head and neck lesions (85 from the oral cavity), 34 invasive oral
      cavity squamous cell carcinomas, as well as 18 invasive tumors known to be HPV
      positive by traditional molecular technology for the presence of HPV-16 DNA using
      real-time quantitative PCR. RESULTS: HPV DNA was detected in 1 of 102
      premalignant lesions (0.98%), 1 of 34 (2.9%) invasive oral cavity carcinomas, and
      14 of 18 (78%) known HPV-positive tumors. CONCLUSIONS: HPV-16 infection and
      integration is seldom found in oral premalignant lesions and invasive carcinoma,
      and therefore rarely contributes to malignant progression in the oral cavity.
      Furthermore, quantitative PCR is a useful technique that reliably excludes
      contaminated samples and those with minimal HPV DNA content that is unlikely to
      be significant in carcinogenesis.

PMID- 12006540
TI  - DNA sequence losses on chromosomes 11p and 18q are associated with clinical
      outcome in lymph node-negative ductal breast cancer.
AB  - PURPOSE: Histological and other markers alone cannot predict the risk of disease
      progression in node-negative breast cancer. Several genomic aberrations have been
      linked to clinical outcome in breast cancer. EXPERIMENTAL DESIGN: In this study,
      comparative genomic hybridization was applied to screen for specific DNA copy
      number gains and losses in 20 pT1/pT2 node-negative invasive ductal carcinomas
      with no disease recurrence with at least 8 years of follow-up and in 20 pT1/pT2
      node-negative tumors with distant disease recurrence. RESULTS: The number of
      genomic aberrations (copy number gains and losses) per tumor was significantly
      higher in tumors with disease recurrence (P < 0.05). The number of genomic
      aberrations was associated with histological grade (P < 0.02). Within the group
      of tumors with disease recurrence, the total number of genetic aberrations per
      tumor (P < 0.02) and the number of DNA sequence losses per tumor (P < 0.01) were
      significantly associated with poor survival. Of the individual loci involved,
      only losses at chromosomes 11p (P < 0.002) and 18q (P < 0.004) were associated
      with poor survival in the recurrence group. Histological grade and loss of 18q
      were independent prognostic variables in multivariate analysis. CONCLUSIONS: This
      genome-wide analysis by comparative genomic hybridization suggests that node
      negative ductal breast cancers with a high number of genomic aberrations have an
      increased risk of disease recurrence. The number of DNA sequence losses,
      particularly losses of chromosomes 11p and 18q, were associated with poor
      prognosis. Genes on chromosomes 11p and 18q may play a role in the progression of
      ductal breast carcinoma.

PMID- 12006541
TI  - Oral (1-->3),(1-->4)-beta-D-glucan synergizes with antiganglioside GD2 monoclonal
      antibody 3F8 in the therapy of neuroblastoma.
AB  - PURPOSE: In vitro beta-glucan can enhance tumor cytotoxicity through iC3b
      receptors on leukocytes. We tested if (1-->3),(1-->4)-beta-D-glucan (beta-glucan)
      can synergize with anti-GD2 monoclonal antibody (MoAb) 3F8 (mouse IgG3) in
      therapy of human neuroblastoma xenografts. EXPERIMENTAL DESIGN: Athymic nude mice
      with established neuroblastoma xenografts were treated with daily i.p. or p.o.
      beta-glucan, in the presence/absence of i.v. MoAb twice a week, for 22-29 days.
      Serial tumor volumes and body weights were monitored. RESULTS: 3F8 plus beta
      glucan produced near-complete tumor regression/disease stabilization, whereas 3F8
      or beta-glucan alone did not significantly affect tumor growth. For NMB7 tumors,
      median survival of 3F8 plus beta-glucan group was 5.5-fold that of control groups
      (P < 0.001), and for LAN-1, the survival difference was 2.6-fold. Forty-seven
      percent of the mice with NMB7 and 18% with LAN-1 remained progression free in
      contrast to <3% of controls. Antitumor effect was seen at > or =40 microg of
      glucan dose, i.v. or p.o., and in all human neuroblastoma cell lines tested. No
      toxicities were noted in mice treated with either beta-glucan alone or 3F8 plus
      beta-glucan (4-4000 microg/dose). In contrast to anti-GD2 MoAb 3G6 (IgM), 3F8
      F(ab')(2) and MoAb 8H9 (IgG1) did not activate complement and had no synergy with
      beta-glucan. Antitumor effect of 3F8 plus p.o. beta-glucan persisted after
      antiasialo-GM1 antibody treatment, as well as in NK-deficient host. CONCLUSIONS:
      p.o. 1,3-1,4-beta-glucan synergized with antitumor IgG and IgM MoAb in vivo.
      Because beta-glucan was well tolerated and inexpensive, its potential value in
      cancer therapy deserves further investigation.

PMID- 12006542
TI  - In vivo pharmacokinetic features, toxicity profile, and chemosensitizing activity
      of alpha-cyano-beta-hydroxy-beta- methyl-N-(2,5-dibromophenyl)propenamide (LFM
      A13), a novel antileukemic agent targeting Bruton's tyrosine kinase.
AB  - The purpose of the present study was to examine the in vivo pharmacokinetics and
      activity of alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)propenamide
      (LFM-A13), a novel antileukemic agent targeting Bruton's tyrosine kinase (BTK).
      We have applied an analytical high-performance liquid chromatography method for
      the quantitative detection of LFM-A13 in plasma samples. Our findings indicate
      that LFM-A13 is quickly absorbed, with the time required to reach the maximum
      plasma drug concentration (t(max)) being 10-18 min after i.p. administration with
      nearly complete bioavailability. LFM-A13 had an elimination half-life of 17-32
      min after i.p. administration at dose levels of 10-50 mg/kg. LFM-A13 exhibited a
      dose-dependent and significant increase in the values of normalized area under
      the curve and maximum concentration (C(max)) as well as a dose-dependent and
      significant decrease in clearance values, suggesting a saturable clearance
      mechanism. LFM-A13 was not toxic to mice when administered systemically at dose
      levels ranging from 10 to 80 mg/kg. Highly effective BTK-inhibitory and apoptosis
      promoting plasma concentrations of LFM-A13 could be achieved in mice without
      toxicity. LFM-A13 exhibited a favorable pharmacokinetic behavior that was not
      adversely affected by the standard chemotherapy drugs vincristine,
      methylprednisolone, or L-asparaginase (when used as combination treatment, VPL)
      and significantly improved the chemotherapy response and survival outcome of mice
      challenged with BCL-1 leukemia cells. Whereas only 14% of mice treated with the
      standard triple-drug combination VPL became long-term survivors, 41% of mice
      treated with this combination plus LFM-A13 survived long-term. LFM-A13 prolonged
      the median survival time of VPL-treated mice from 37 to 58 days. Our results
      confirm and extend previous studies regarding the role of BTK chemotherapy
      resistance of B-lineage leukemic cells (S. Mahajan et al., J. Biol. Chem., 274:
      9587-9599, 1999). BTK inhibitors such as LFM-A13 may be useful as a new class of
      chemosensitizing and apoptosis-promoting antileukemic agents for treatment of
      patients with chemotherapy-resistant B-lineage leukemias or lymphomas.

PMID- 12006544
TI  - Detoxification of the polyamine analogue N1-ethyl-N11-[(cycloheptyl)methy]-4,8
      diazaundecane (CHENSpm) by polyamine oxidase.
AB  - PURPOSE: Analogues of the naturally occurring polyamines, alkylated on both
      terminal amines, are being developed as anticancer drugs. Because bisalkylated
      derivatives of putrescine (1,4-diaminobutane) are potent inhibitors of the flavin
      adenine dinucleotide-dependent polyamine oxidase (PAO), we asked whether PAO
      could detoxify synthetic bisalkylated polyamines with chain lengths longer than
      putrescine. EXPERIMENTAL DESIGN: We investigated the effects of one polyamine
      analogue in Chinese hamster ovary (CHO) and HCT116 human colon tumor-derived
      cells, which express dramatically different levels of PAO activity, and in these
      same cells treated with an inhibitor of PAO. RESULTS: Concentrations of N1-ethyl
      N11-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm), ranging from 0.3 to 10
      microM, caused growth arrest and reduced cell survival in HCT116 cells but not in
      CHO cells. This cell line-specific difference in CHENSpm toxicity was not
      attributable to differences in analogue uptake, because intracellular levels of
      the drug were similar in CHO and HCT116 cells treated with equivalent
      concentrations of CHENSpm in the presence of MDL 72,527, a specific inhibitor of
      PAO. The PAO inhibitor, in combination with CHENSpm, caused a significant
      increase in intracellular CHENSpm levels and increased growth inhibition and cell
      damage in CHO cells but not in HCT116 cells. CHO cells, but not HCT116 cells,
      produced two primary amine-containing metabolites from CHENSpm that were
      suppressed by MDL 72,527. CONCLUSIONS: These data demonstrate that CHENSpm is
      detoxified in PAO-expressing CHO cells, but not in PAO-deficient HCT116 cells, by
      a mechanism yielding products containing free primary amine groups and implicate
      PAO as the detoxification enzyme. Because other studies suggest that PAO may be
      self-regulated in some tumors, differential expression of PAO may be the basis
      for selective toxicity of CHENSpm and other N-substituted polyamine analogues in
      certain cancers.

PMID- 12006543
TI  - Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells:
      relevance to mechanism of therapeutic action.
AB  - PURPOSE: Bexarotene is the first synthetic rexinoid approved for the treatment of
      all stages of cutaneous T-cell lymphoma (CTCL) however the mechanism of
      bexarotene action is unknown. We examined the effects of bexarotene on induction
      of apoptosis and expression of its cognate receptors in well-established CTCL
      cell lines (MJ, Hut78, and HH). EXPERIMENTAL DESIGN: CTCL cells were treated with
      0.1, 1, and 10 microM bexarotene for 24, 48, 72, and 96 h. Apoptosis was
      determined by flow-cytometry analysis of sub-G(1) hypodiploid nuclei and annexin
      V binding populations. Apoptosis-associated proteins and retinoid receptors were
      detected by Western blots. RESULTS: Bexarotene treatment at 1 and 10 microM for
      96 h increased the number of cells with sub-G1 populations and annexin V binding
      in a dose-dependent manner compared with vehicle controls (DMSO) in all three
      cell lines, respectively. Bexarotene treatment suppressed the expression of
      retinoid X receptor alpha and retinoic acid receptor alpha proteins in all three
      lines compared with untreated controls. Bexarotene treatment decreased the
      protein levels of survivin, activated caspase-3, and cleaved poly(ADP-Ribose)
      polymerase, but had no obvious effect on expression of Fas/Fas ligand and bcl-2
      proteins in all three CTCL lines. CONCLUSIONS: Bexarotene treatment at clinically
      relevant concentrations causes apoptosis of CTCL cell lines in association with
      activation of caspase-3 and cleavage of poly(ADP-Ribose) polymerase, as well as
      down-regulation of retinoid X receptor alpha, retinoic acid receptor alpha, and
      survivin. These findings support apoptosis as a mechanism for bexarotene therapy
      in CTCL.

PMID- 12006545
TI  - Overexpression of PTEN increases sensitivity to SN-38, an active metabolite of
      the topoisomerase I inhibitor irinotecan, in ovarian cancer cells.
AB  - PURPOSE: PTEN is a tumor suppressor gene that was identified on chromosome 10q23.
      In addition to its original function as a tumor suppressor, this gene product was
      recently reported to enhance the sensitivity of cancer cells to anticancer
      agents. It is for the purpose of this study to investigate its function and the
      mechanisms by which PTEN enhances the sensitivity of ovarian cancer to antitumor
      agents. EXPERIMENTAL DESIGN: PTEN cDNA was introduced into the ovarian cancer
      cell line SHIN-3 and a high-expression cell line (SHIN-3/PTEN) was established.
      This cell line and a control were further analyzed. RESULTS: SHIN-3 cells did not
      carry any mutations in its genome after sequencing. In vitro examination of
      sensitivity to anticancer agents showed that the 50% growth-inhibitory
      concentration value for irinotecan metabolite (SN-38) in SHIN-3/PTEN was 800 nM,
      a 6.6-fold higher sensitivity compared with that of the control (5300 nM). There
      were no differences in sensitivity to cisplatin, paclitaxel, or gemcitabine
      between SHIN-3/PTEN and the controls. The percentage of apoptotic cells in SHIN
      3/PTEN was 16.6 +/- 0.7% 24 h after addition of SN-38, a significant increase
      over controls (8.6 +/- 0.9%; P < 0.01). Lower topoisomerase I activity was
      observed in SHIN-3/PTEN, compared with controls. CONCLUSIONS: These results
      indicate that high PTEN expression enhances the sensitivity of ovarian cancer
      cells to irinotecan and the induction of apoptosis and the suppression of
      topoisomerase I activity in cancer cells are suggested as possible mechanisms
      attributable to high PTEN expression.

PMID- 12006546
TI  - Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody
      ImClone C225 in androgen-independent prostate cancer growing orthotopically in
      nude mice.
AB  - In human androgen-independent prostate cancer (PCa), epidermal growth factor
      receptor (EGFR) regulates angiogenesis, tumor growth, and progression. In this
      study, we evaluated whether the blockade of EGFR by the anti-EGFR antibody
      ImClone C225 (IMC-C225) inhibited tumor growth and metastasis by inhibiting
      angiogenesis, and whether paclitaxel enhanced the results of therapy in androgen
      independent PCa. PC-3M-LN4 PCa cells were implanted orthotopically in athymic
      nude mice and treated with i.p. IMC-C225 (1 mg twice a week) and/or paclitaxel
      (200 microg once a week). In vitro treatment of PC-3M-LN4 with IMC-C225 inhibited
      EGFR autophosphorylation without any significant antiproliferative effect. In
      contrast, in vivo therapy with IMC-C225 alone (P < 0.05) or in combination with
      paclitaxel (P < 0.005) significantly inhibited PCa growth and metastasis. Serum
      levels of interleukin (IL) 8 were lower after therapy, and IL-8 mRNA expression
      was down-regulated within the tumors after therapy. The down-regulation of IL-8
      correlated with reduced microvessel density. IMC-C225 reduced tumor cell
      proliferation, enhanced p27(kip1) expression, and induced tumor and endothelial
      cell apoptosis. These studies indicate that IMC-C225 has significant antitumor
      effect in this murine model, mediated in part by inhibition of cellular
      proliferation and angiogenesis, and by enhancement of apoptosis. The simultaneous
      administration of paclitaxel enhanced this effect.

PMID- 12006547
TI  - Erythropoietin restores the antitumor effectiveness of photodynamic therapy in
      mice with chemotherapy-induced anemia.
AB  - PURPOSE: The study was designed to examine the impact of anemia on the antitumor
      efficacy of photodynamic therapy (PDT) in a murine colon-26 adenocarcinoma model
      syngeneic with BALB/c mice. EXPERIMENTAL DESIGN: Acute hemolytic anemia was
      induced by a single i.p. injection of phenylhydrazine hydrochloride (150 mg/kg).
      Anemia induced by i.p. administration of carboplatin (100 mg/kg) was corrected by
      s.c. treatment with recombinant human erythropoietin (1000 units/kg/day). The
      effectiveness of PDT (10 mg/kg Photofrin, 150 J/cm2 laser dose) was evaluated by
      measurements of the footpad edema and tumor volume. All of the RBC-related
      parameters were measured from the tail vein. RESULTS: Phenylhydrazine
      hydrochloride injection resulted in a blunted response of normal tissues to
      Photofrin-mediated PDT-induced edema formation. Similarly, the antitumor response
      in mice with hemolytic anemia was nearly completely abrogated. The antitumor
      effectiveness of PDT was also significantly diminished in a more realistic
      clinical situation when anemia was induced by administration of carboplatin.
      Importantly, administration of recombinant human erythropoietin completely
      restored the sensitivity of the tumor to PDT in carboplatin-treated mice.
      CONCLUSIONS: These results indicate that anemia can negatively influence the
      therapeutic effectiveness of PDT. For optimal antitumor response anemia should be
      corrected before PDT procedure.

PMID- 12006548
TI  - Overexpression of HER-2/neu in uterine serous papillary cancer.
AB  - PURPOSE: Uterine serous papillary carcinoma (USPC) is a highly aggressive variant
      of endometrial cancer and histologically similar to high-grade ovarian cancer.
      HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is
      overexpressed by immunohistology in approximately 25% of ovarian cancers. In this
      study, we have evaluated the expression of HER-2/neu in several fresh,
      established, paraffin-embedded, fixed USPCs. In addition, we have tested the
      sensitivity of USPC cells to Herceptin treatment. EXPERIMENTAL DESIGN: Ten
      consecutive USPC specimens were assessed by immunohistochemistry for the
      intensity of expression of HER-2/neu. In addition, three USPC cell lines were
      analyzed for expression of HER-2/neu by flow cytometry as well as for sensitivity
      to Herceptin-mediated, complement-dependent cytotoxicity, antibody-dependent
      cellular cytotoxicity (ADCC), and inhibition of cell proliferation. RESULTS:
      Eight of 10 (80%) of the USPCs assessed immunohistochemically for the intensity
      of expression of HER-2/neu stained heavily for HER-2/neu (2+ to 3+). Fresh and
      established primary USPC cell lines were found to express significantly more HER
      2/neu receptor by flow cytometry (on the average, 10-fold greater) when compared
      with HER-2/neu-positive primary or established breast and ovarian cancer cell
      lines (P < 0.001). Importantly, although these USPC cell lines were resistant to
      chemotherapy in vivo and to natural killer- and complement-mediated cytotoxicity
      in vitro, they were found to be highly sensitive to Herceptin-mediated ADCC. USPC
      cell proliferation was also inhibited by Herceptin. A significant enhancement of
      ADCC was demonstrated when effector cells were exposed to low doses of IL-2 in
      vitro. Physiological concentrations of human serum IgG did not inhibit Herceptin
      mediated ADCC against USPC. CONCLUSIONS: On the basis of these findings and
      previous reports showing a positive in vivo correlation between efficacy of
      Herceptin therapy and the level of HER-2/neu overexpression by tumor cells, we
      propose that Herceptin might be a novel and attractive therapeutic strategy in
      patients harboring chemotherapy-resistant, recurrent, or metastatic USPC.

PMID- 12006549
TI  - Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell
      lines in vitro and in vivo and produces synergistic growth inhibition in
      combination with other antitumor agents.
AB  - Small cell lung cancers (SCLCs), many non-SCLCs, and other cancers have
      neuroendocrine features, including paracrineand autocrine growth stimulation by
      various neuropeptides. Interference with this pathway is an attractive target for
      novel therapies. We developed a novel bradykinin antagonist dimer, CU201 (B9870),
      that acts as a "biased agonist" for neuropeptides by blocking G(alphaq) signaling
      and activating G(alpha12,13) signaling. CU201 induced apoptosis and complete
      growth inhibition in various lung cancer and other cancer cell lines. CU201 was
      10-fold more potent than substance P derivatives and was stable in serum for >7
      days. In this study, we evaluated the ability of CU201 to produce additive or
      synergistic growth inhibition in combination with various antitumor agents used
      in lung cancer therapy. We found that CU201 produced additive or synergistic
      growth inhibition when combined with doxorubicin, etoposide, cisplatin,
      vinorelbine, and paclitaxel for SCLC lines and with paclitaxel and ZD1839, an
      epidermal growth factor receptor tyrosine kinase inhibitor, for non-SCLC cell
      lines. Pharmacokinetic parameters associated with the i.v. administration of
      CU201 were evaluated in normal mice, and the effects of CU201 on the growth of
      human lung cancer xenografts were evaluated in athymic nude mice. In CD2F1 mice
      given an i.v. bolus infusion of 5 mg/kg, the c(max) was 5773 ng/ml (5 microM),
      and the decay was biexponential. When fitted to a two-compartment model, the
      t(1/2alpha) was 14.4 min, and the t(1/2beta) was 44.3 h, indicating a long
      terminal half-life consistent with the prolonged in vitro effects. CU201
      inhibited the growth of human lung cancers in athymic nude mice by the
      intratumoral, s.c., and i.p. routes at a dose of 5 mg/kg/day. This dose is >10
      fold less than the dose of substance P derivatives used to inhibit SCLC
      xenografts in nude mice. We conclude that CU201 should undergo further
      preclinical toxicology studies in its development as a novel targeted therapy for
      the treatment of lung cancers with neuroendocrine features. These studies are in
      progress through the NCI RAID mechanism.

PMID- 12006550
TI  - Nuclear receptor agonists as potential differentiation therapy agents for human
      osteosarcoma.
AB  - PURPOSE: This study was designed to investigate whether nuclear receptor agonists
      can be used as potential differentiation therapy agents for human osteosarcoma.
      EXPERIMENTAL DESIGN: Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE
      85) were treated with proliferator-activated receptor (PPAR)gamma agonists,
      troglitazone and ciglitazone, and a retinoid X receptor (RXR) ligand, 9-cis
      retinoic acid. The proliferation and induction of apoptosis in the treated cells
      were assessed, as was the induction of alkaline phosphatase, a differentiation
      marker of osteoblasts. RESULTS: The expression of PPARgamma was readily detected
      in all tested osteosarcoma lines. On treatment with the PPARgamma and RXR
      ligands, all four osteosarcoma lines exhibited a significantly reduced
      proliferation rate and cell viability. Among the four lines, 143B and MNNG/HOS
      were shown to be more sensitive to ligand-induced apoptosis, as demonstrated by
      the Crystal Violet and Hoechst staining assays. Of the three tested ligands,
      troglitazone was shown to be the most effective in inducing cell death, followed
      by 9-cis retinoic acid. Moreover, a strong synergistic effect on the induction of
      cell death was observed when both troglitazone and 9-cis retinoic acid or
      ciglitazone and 9-cis retinoic acid were administered to osteosarcoma cells.
      Troglitazone was shown to effectively induce alkaline phosphatase activity, a
      well-characterized hallmark for osteoblastic differentiation. CONCLUSIONS: Our
      findings suggest that PPARgamma and/or RXR ligands may be used as efficacious
      adjuvant therapeutic agents for primary osteosarcoma, as well as potential
      chemopreventive agents for preventing the recurrence and metastasis of
      osteosarcoma after the surgical removal of the primary tumors.

PMID- 12006551
TI  - Selective exclusion by the polyamine transporter as a mechanism for differential
      radioprotection of amifostine derivatives.
AB  - Amifostine metabolites WR-1065 and the disulfide WR-33278 are thiol-containing
      polyamine analogues with potent radio- and chemoprotective properties. Some
      studies suggest that amifostine exerts differential cytoprotection in normal
      versus neoplastic tissues, but this finding remains controversial. To assess the
      role of the polyamine transport system in radioprotection by amifostine
      derivatives, human DU-145 prostate cancer cells were transfected with a cDNA that
      encodes antizyme (OAZ), a polyamine-inducible protein that suppresses polyamine
      transport under control of a minimal heat shock promoter. Selected clones
      expressing OAZ displayed heat shock-dependent suppression of polyamine uptake.
      When added to culture medium under nonreducing conditions, both WR-1065 and WR
      33278 were detected as the disulfide form. Each derivative protected both
      parental and OAZ-transfected DU-145 cells from X-ray-induced cell killing at 37
      degrees C. When cultures were heat shocked at 42 degrees C, both derivatives
      protected parental, but not OAZ-transfected cells from radiation-induced cell
      killing. Treatment of DU-145 cells with difluoromethylornithine (DFMO) suppressed
      intracellular putrescine and spermidine content, but increased the uptake of WR
      33278-derived aminothiols. The concentration-dependent radioprotection of DU-145
      cells by WR-33278 was enhanced by DFMO. Addition of exogenous putrescine reduced
      WR-33278-mediated radioprotection in both DFMO-treated and untreated DU-145
      cells. These data demonstrate that negative regulation of the polyamine
      transporter, mediated by polyamines or antizyme, suppresses the uptake and
      radioprotective activity of amifostine derivatives. Selective exclusion of
      amifostine derivatives by the polyamine transporter could account for
      differential radio- or chemoprotection in normal versus neoplastic tissues in
      specific situations.

PMID- 12006552
TI  - Modulation of marrow proliferation and chemosensitivity by tumor-produced
      cytokines from syngeneic pancreatic tumor lines.
AB  - PURPOSE: A dynamic process exists in which hematopoietic progenitor andstromal
      cells interact to maintain normal hematopoiesis or to adjust to hematopoietic
      needs under "stress" situations. The effect that tumor-produced growth factors
      have on hematopoiesis has not been addressed. We postulate that an excess of
      tumor-produced stimulatory or inhibitory cytokines could impact marrow
      proliferation and sensitivity to cytotoxic agents. METHODS: We used two tumor
      lines (TGP47 and TGP51) taken from a panel of syngeneic murine pancreatic
      carcinomas, in which each produces a unique array of cytokines, and evaluated
      their effect in vitro on marrow proliferation and chemosensitivity. RESULTS:
      TGP51- and TGP47-conditioned medium increased [3H]thymidine incorporation into
      cultured marrow cells by approximately 12-fold and 4.8-fold, respectively. The
      percent of cells in the S + G2-M phases of the cell cycle increased by 110%
      (TGP51) and 44% (TGP47), and the MCF for proliferating cell nuclear antigen
      expression increased by 104% (TGP51) and 45% (TGP47). Marrow proliferation of
      untreated cells could be reduced by interleukin 6 but not by granulocyte
      macrophage colony-stimulating factor neutralization. Conditioned medium-induced
      stimulation was unchanged by either interleukin 6alpha or granulocyte macrophage
      colony-stimulating factor alpha. FLT3-Lalpha reduced marrow proliferation induced
      by TGP51 medium. Addition of FLT3-L to TGP47 medium additionally enhanced the
      marrow proliferation. Antitumor necrosis factor alpha additionally increased
      marrow proliferation induced by TGP47 and TGP51 conditioned medium, whereas
      addition of tumor necrosis factor alpha reduced marrow proliferation associated
      with TGP51 medium. The TGP51-induced increase in marrow proliferation resulted in
      increased marrow chemosensitivity to three myelosuppressive drugs: doxorubicin,
      cyclophosphamide, and CPT-11, decreasing the IC50 by 46%, 38%, and 95%,
      respectively. CONCLUSION: Tumor-produced cytokines can affect marrow
      proliferative activity and, thus, chemosensitivity to three distinct classes of
      chemotherapeutics.

PMID- 12006553
TI  - Correspondence re: M. Follen et al., a randomized clinical trial of 4
      hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the
      cervix.

PMID- 12006555
TI  - Correspondence re: Raida, M. et al., prevalence of a common point mutation in the
      dihydropyrimidine dehydrogenase (DPD) gene within the 5'-splice donor site of
      intron 14 in patients with severe 5-fluorouracil (5-FU)-related toxicity compared
      with controls.

PMID- 12006557
TI  - Inhibition of major histocompatibility complex class II gene transcription by
      nitric oxide and antioxidants.
AB  - Interferon (IFN)-gamma facilitates cellular immune response, in part, by inducing
      the expression of major histocompatibility complex class II (MHC-II) molecules.
      We demonstrate that IFN-gamma induces the expression of HLA-DRA in vascular
      endothelial cells via mechanisms involving reactive oxygen species. IFN-gamma
      induced HLA-DRA expression was inhibited by nitric oxide (NO) and antioxidants
      such as superoxide dismutase, catalase, pyrrolidine dithiocarbamate, and N
      acetylcysteine. Nuclear run-on assays demonstrated that NO and antioxidants
      inhibited IFN-gamma-induced HLA-DRA gene transcription. Transient transfection
      studies using a fully functional HLA-DRA promoter construct ([-300]DR alpha.CAT)
      showed that inhibition of endogenous NO synthase activity by N(omega)-monomethyl
      l-arginine or addition of exogenous hydrogen peroxide (H(2)O(2)) augmented basal
      and IFN-gamma-stimulated [-300]DR alpha.CAT activity. However, H(2)O(2) and
      N(omega)-monomethyl-l-arginine could induce HLA-DRA expression suggesting that
      H(2)O(2) is a necessary but not a sufficient mediator of IFN-gamma-induced HLA
      DRA expression. Electrophoretic mobility shift assay and Western blotting
      demonstrated that NO and antioxidants had little or no effect on IFN-gamma
      induced IRF-1 activation or MHC-II transactivator (CIITA) expression but did
      inhibit IFN-gamma-induced activation of STAT1 alpha (p91) and Y box transcription
      factors, NF-Y(A) and NF-Y(B). These results indicate that NO and antioxidants may
      attenuate vascular inflammation by antagonizing the effects of intracellular
      reactive oxygen species generation by IFN-gamma, which is necessary for MHC-II
      gene transcription.

PMID- 12006558
TI  - Ribozyme inhibition of alphavirus replication.
AB  - A model system to examine the expression and antiviral activity of trans-acting
      ribozymes in mammalian cells has been developed and evaluated. Hairpin ribozymes
      were engineered to cleave a specific site, identified by a combinatorial activity
      based selection method, within genomic and subgenomic RNA species of Sindbis
      virus. Transiently transfected cells expressed moderate levels of ribozyme
      (approximately 50,000 molecules/cell) with predominant nuclear localization and a
      short half-life (23 min). Stable cell lines expressed ribozymes at modest levels
      (approximately 2,000 molecules/cell). Ribozyme-mediated RNA cleavage activity was
      detected in cell extracts. Clonal cell lines were challenged with recombinant
      Sindbis virus, and viral replication was examined using plaque formation and
      green fluorescent protein assays. Significant inhibition of viral replication was
      observed in cells expressing the active antiviral ribozyme, and lower levels of
      inhibition in control cells expressing inactive or irrelevant ribozymes. These
      findings are consistent with a model in which inhibition of viral replication
      occurs via ribozyme cleavage of viral RNAs, suggesting that ribozymes may
      represent useful antiviral agents.

PMID- 12006559
TI  - Nephrocystin-conserved domains involved in targeting to epithelial cell-cell
      junctions, interaction with filamins, and establishing cell polarity.
AB  - Nephrocystin is the protein product of the gene mutated in juvenile
      nephronophthisis, an autosomal recessive cystic kidney disease afflicting
      children and young adults. Because the normal cellular function of nephrocystin
      is largely unknown, the molecular defects underlying disease pathogenesis remain
      obscure. Analysis of nephrocystin amino acid sequences from human and other
      species revealed three distinct conserved domains including Src homology 3 and
      coil-coil domains in the N-terminal region, as well as a large highly conserved C
      terminal region bearing no obvious homology to other proteins and hence referred
      to as the "nephrocystin homology domain" (NHD). The objective of this study was
      to gain insight into nephrocystin function by defining functional properties of
      the conserved domains. We analyzed a series of nephrocystin deletion mutants
      expressed in Madin-Darby canine kidney and COS-7 cells. This analysis revealed
      previously unrecognized functional attributes of the NHD, including abilities to
      promote both self-association and epithelial cell-cell junctional targeting. We
      further observed that Madin-Darby canine kidney cell lines stably expressing a
      nephrocystin mutant with a deletion of the Src homology 3 domain have reduced
      ability to establish tight junctions as measured by transepithelial electrical
      resistance. Finally, from a two-hybrid screen and coimmunoprecipitation studies
      we identified members of the filamin family of actin-binding proteins as having
      the capacity to interact with the NHD. These findings support a functional role
      for nephrocystin as a docking protein involved in organizing a protein complex to
      regulate the actin cytoskeleton at sites of epithelial cell-cell adhesion and
      further suggest that these properties are important for establishing epithelial
      cell polarity.

PMID- 12006560
TI  - Mismatch repair in human nuclear extracts. Quantitative analyses of excision of
      nicked circular mismatched DNA substrates, constructed by a new technique
      employing synthetic oligonucleotides.
AB  - Mammalian mismatch repair (MMR) systems respond to broad ranges of DNA mismatches
      and lesions. Kinetic analyses of MMR processing in vitro have focused on base
      mismatches in a few sequence contexts, because of a lack of general and
      quantitative MMR assays and because of the difficulty of constructing a
      multiplicity of MMR substrates, particularly those with DNA lesions. We describe
      here simple and efficient construction of 11 different MMR substrates, by
      ligating synthetic oligomers into gapped plasmids generated using sequence
      specific N.BstNBI nicking endonuclease, then using sequence-specific nicking
      endonuclease N.AlwI to introduce single nicks for initiation of 3' to 5' or 5' to
      3' excision. To quantitatively assay MMR excision gaps in base-mispaired
      substrates, generated in human nuclear extracts lacking exogenous dNTPs, we used
      position- and strand-specific oligomer probes. Mispair-provoked excision along
      the shorter path from the pre-existing nick toward the mismatch, either 3' to 5'
      or 5' to 3', predominated over longer path excision by roughly 10:1 to 20:1. MMR
      excision was complete within 7 min, was highly specific (90:1) for the nicked
      strand, and was strongly mispair-dependent (at least 40:1). Nonspecific (mismatch
      independent) 5' to 3' excision was considerably greater than nonspecific 3' to 5'
      excision, especially at pre-existing gaps, but was not processive. These
      techniques can be used to construct and analyze MMR substrates with DNA
      mismatches or lesions in any sequence context.

PMID- 12006561
TI  - Mismatch repair in human nuclear extracts. Time courses and ATP requirements for
      kinetically distinguishable steps leading to tightly controlled 5' to 3' and
      aphidicolin-sensitive 3' to 5' mispair-provoked excision.
AB  - Mismatch repair (MMR) systems enhance genomic stability by correcting DNA
      replication errors. The events in mammalian MMR pathways remain poorly
      understood. Using HeLa cell nuclear extracts, we analyzed correction of mispairs
      in circular DNA substrates with single defined nicks and measured excision in the
      absence of exogenous dNTPs by annealing specific oligonucleotide probes. In
      reactions initiated by concomitant temperature shift and addition of ATP or
      Mg(2+) to otherwise complete mixtures on ice, ATP-initiated excision and final
      error correction lagged behind Mg(2+)-initiated reactions, suggesting a very
      early requirement for ATP but not its hydrolysis. Subsequent stable commitment
      (resistance to added excess competitor substrate) began within 30 s, required
      hydrolyzable ATP, and plateaued after 60-70 s. This may reflect formation of
      hydrolysis-dependent translocating and/or pre-excision complexes. Excision along
      shorter nick-mispair paths began 15 s later than commitment. Both 3' to 5' and 5'
      to 3' excision gaps appeared at rates of approximately 0.0055 of final yields per
      second, respectively, 30 or 2.5 times the nonspecific excision rates. The lag
      between 3' to 5' excision gaps at two different positions yielded an excision
      progress rate of 5.2 nucleotides/s. In both substrates, corrected products
      appeared at fractional rates of 0.0027 of final yield per second. Aphidicolin,
      known to inhibit both the DNA synthesis and 3' to 5' exonuclease activities of
      polymerases delta and epsilon, reduced appearance of 3' to 5' excision tracts
      roughly 4-fold at 90 microm but had no effect on 5' to 3' excision.

PMID- 12006562
TI  - Ceramide channels increase the permeability of the mitochondrial outer membrane
      to small proteins.
AB  - Ceramides are known to play a major regulatory role in apoptosis by inducing
      cytochrome c release from mitochondria. We have previously reported that C(2)-
      and C(16)-ceramide, but not dihydroceramide, form large channels in planar
      membranes (Siskind, L. J., and Colombini, M. (2001) J. Biol. Chem. 275, 38640
      38644). Here we show that ceramides do not trigger a cytochrome c secretion or
      release mechanism, but simply raise the permeability of the mitochondrial outer
      membrane, via ceramide channel formation, to include small proteins. Exogenously
      added reduced cytochrome c was able to freely permeate the mitochondrial outer
      membrane with entry to and exit from the intermembrane space facilitated by
      ceramides in a dose- and time-dependent manner. The permeability pathways were
      eliminated upon removal of C(2)-ceramide by bovine serum albumin, thus ruling out
      a detergent-like effect of C(2)-ceramide on membranes. Ceramide channels were not
      specific to cytochrome c, as ceramides induced release of adenylate kinase, but
      not fumerase from isolated mitochondria, showing some specificity of these
      channels for the outer mitochondrial membrane. SDS-PAGE results show that
      ceramides allow release of intermembrane space proteins with a molecular weight
      cut-off of about 60,000. These results indicate that the ceramide-induced
      membrane permeability increases in isolated mitochondria are via ceramide channel
      formation and not a release mechanism, as the channels that allow cytochrome c to
      freely permeate are reversible, and are not specific to cytochrome c.

PMID- 12006563
TI  - Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE
      domains of Vps27p and Hrs.
AB  - The FYVE domain mediates the recruitment of proteins involved in membrane
      trafficking and cell signaling to phosphatidylinositol 3-phosphate (PtdIns(3)P)
      containing membranes. To elucidate the mechanism by which the FYVE domain
      interacts with PtdIns(3)P-containing membranes, we measured the membrane binding
      of the FYVE domains of yeast Vps27p and Drosophila hepatocyte growth factor
      regulated tyrosine kinase substrate and their mutants by surface plasmon
      resonance and monolayer penetration analyses. These measurements as well as
      electrostatic potential calculation show that PtdIns(3)P specifically induces the
      membrane penetration of the FYVE domains and increases their membrane residence
      time by decreasing the positive charge surrounding the hydrophobic tip of the
      domain and causing local conformational changes. Mutations of hydrophobic
      residues located close to the PtdIns(3)P-binding pocket or an Arg residue
      directly involved in PtdIns(3)P binding abrogated the penetration of the FYVE
      domains into the monolayer, the packing density of which is comparable with that
      of biological membranes and large unilamellar vesicles. Based on these results,
      we propose a mechanism of the membrane binding of the FYVE domain in which the
      domain first binds to the PtdIns(3)P-containing membrane by specific PtdIns(3)P
      binding and nonspecific electrostatic interactions, which is then followed by the
      PtdIns(3)P-induced partial membrane penetration of the domain.

PMID- 12006564
TI  - Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in
      endometrial stromal cells by malignant endometrial epithelial cells. A paracrine
      effect mediated by prostaglandin E2 and nuclear factor-kappa B.
AB  - We investigated the regulation of prostaglandin production in normal endometrial
      stromal cells (ESC) by malignant endometrial epithelial cells. We found that
      cyclooxygenase (COX)-2 mRNA and protein levels and prostaglandin (PG)E(2)
      production in ESC were significantly increased by Ishikawa malignant endometrial
      epithelial cell conditioned medium (MECM). By using transient transfection
      assays, we found that the -360/-218-bp region of the COX-2 promoter gene was
      critical for MECM induction of promoter activity. This MECM-responsive region
      contained a variant nuclear factor (NF)-kappa B site at -222 to -213 that, when
      mutated, completely abolished COX-2 promoter activation by MECM. Employing
      electrophoretic mobility shift assays, we further demonstrated that binding of NF
      kappa B p65 to this NF-kappa B-binding site is, in part, responsible for the COX
      2 promoter activation by MECM. To investigate further the potential effects of
      MECM on COX-2 mRNA stability, ESC were treated with MECM in the absence or
      presence of actinomycin D, a general transcription inhibitor. We found that MECM
      significantly increased COX-2 mRNA stability. Intriguingly, we found that PGE(2)
      was one of the major factors in MECM, which was responsible for up-regulating COX
      2 expression in ESC. ECC-1 and HEC-1A malignant endometrial epithelial cell lines
      also produced significantly increased quantities of PGE(2). In conclusion,
      malignant endometrial epithelial cells secrete PGE(2) that induces COX-2
      expression in normal endometrial stromal cells in a paracrine fashion through
      activation of transcription and stabilization of COX-2 mRNA.

PMID- 12006565
TI  - Structural and enzymatic properties of the AAA protein Drg1p from Saccharomyces
      cerevisiae. Decoupling of intracellular function from ATPase activity and
      hexamerization.
AB  - The AAA protein Drg1 from yeast was affinity-purified, and its ATPase activity
      and hexamerization properties were analyzed. The same parameters were also
      determined for several mutant proteins and compared in light of the growth
      characteristics of the corresponding cells. The protein from a thermosensitive
      mutant exhibited reduced ATPase activity and hexamerization. These defects were
      not reversed by an intragenic suppressor mutation, although this allele supported
      growth at the nonpermissive temperature. A different set of mutants was generated
      by site-specific mutagenesis intended to adjust the Walker A box of the D2 domain
      of Drg1p to that of the D1 domain. A S562G exchange in D2 produced a
      nonfunctional protein that did not hexamerize but showed above-normal ATPase
      activity. The C561T mutant protein, on the other hand, was functional but
      hexamerized less readily and had reduced ATPase activity. In contrast, the
      C561T/S562G protein hexamerized less than wild type but had much higher ATPase
      activity. We distinguished strong and weak ATP-binding sites in the wild type
      protein but two weak sites in the C561T/S562G protein, indicating that the
      stronger site resides in D2. These observations are discussed in terms of the
      inter-relationship of ATPase activity per se, oligomeric status, and
      intracellular function for AAA proteins.

PMID- 12006566
TI  - Transcriptional regulation in constraints-based metabolic models of Escherichia
      coli.
AB  - Full genome sequences enable the construction of genome-scale in silico models of
      complex cellular functions. Genome-scale constraints-based models of Escherichia
      coli metabolism have been constructed and used to successfully interpret and
      predict cellular behavior under a range of conditions. These previous models do
      not account for regulation of gene transcription and thus cannot accurately
      predict some organism functions. Here we present an in silico model of the
      central E. coli metabolism that accounts for regulation of gene expression. This
      model accounts for 149 genes, the products of which include 16 regulatory
      proteins and 73 enzymes. These enzymes catalyze 113 reactions, 45 of which are
      controlled by transcriptional regulation. The combined metabolic/regulatory model
      can predict the ability of mutant E. coli strains to grow on defined media as
      well as time courses of cell growth, substrate uptake, metabolic by-product
      secretion, and qualitative gene expression under various conditions, as indicated
      by comparison with experimental data under a variety of environmental conditions.
      The in silico model may also be used to interpret dynamic behaviors observed in
      cell cultures. This combined metabolic/regulatory model is thus an important step
      toward the goal of synthesizing genome-scale models that accurately represent E.
      coli behavior.

PMID- 12006567
TI  - Nitric oxide uptake by erythrocytes is primarily limited by extracellular
      diffusion not membrane resistance.
AB  - The process of NO transfer into erythrocytes (RBCs) is of critical biological
      importance because it regulates the bioavailability and diffusional distance of
      endothelial-derived NO. It has been reported that the rate of NO reaction with
      oxyhemoglobin (Hb) within RBCs is nearly three orders of magnitude slower than
      that by equal amounts of free oxyhemoglobin. Consistent with early studies on
      oxygen uptake by RBCs, the process of extracellular diffusion was reported to
      explain this much lower NO uptake by RBC encapsulated Hb (Liu, X., Miller, M. J.,
      Joshi, M. S., Sadowska-Krowicka, H., Clark, D. A., and Lancaster, J. R., Jr.
      (1998) J. Biol. Chem. 273, 18709-18713). However, it was subsequently proposed
      that the RBC membrane provides the main resistance to NO uptake rather than the
      process of extracellular diffusion (Vaughn, M. W., Huang, K. T., Kuo, L., and
      Liao, J. C. (2000) J. Biol. Chem. 275, 2342-2348). This conclusion was based on
      competition experiments that were assumed to be able to determine the rate
      constant of NO uptake by RBCs without extracellular diffusion limitation. To test
      the validity of this hypothesis, we theoretically analyzed competition
      experiments. Here, we show that competition experiments do not eliminate the
      extracellular diffusion limitation. Simulation of the competition data indicates
      that the main resistance to NO uptake by RBCs is caused by extracellular
      diffusion in the unstirred layer surrounding each RBC but not by the RBC
      membrane. This extracellular diffusion resistance is responsible for preventing
      interference of NO signaling in the endothelium without the need for special NO
      uptake by intracellular hemoglobin or a unique membrane resistance mechanism.

PMID- 12006568
TI  - The bacterial histone-like protein HU specifically recognizes similar structures
      in all nucleic acids. DNA, RNA, and their hybrids.
AB  - HU, a major component of the bacterial nucleoid, shares properties with histones,
      high mobility group proteins (HMGs), and other eukaryotic proteins. HU, which
      participates in many major pathways of the bacterial cell, binds without sequence
      specificity to duplex DNA but recognizes with high affinity DNA repair
      intermediates. Here we demonstrate that HU binds to double-stranded DNA, double
      stranded RNA, and linear DNA-RNA duplexes with a similar low affinity. In
      contrast to this nonspecific binding to total cellular RNA and to supercoiled
      DNA, HU specifically recognizes defined structures common to both DNA and RNA. In
      particular HU binds specifically to nicked or gapped DNA-RNA hybrids and to
      composite RNA molecules such as DsrA, a small non-coding RNA. HU, which modulates
      DNA architecture, may play additional key functions in the bacterial machinery
      via its RNA binding capacity. The simple, straightforward structure of its
      binding domain with two highly flexible beta-ribbon arms and an alpha-helical
      platform is an alternative model for the elaborate binding domains of the
      eukaryotic proteins that display dual DNA- and RNA-specific binding capacities.

PMID- 12006569
TI  - Variant forms of alpha-fetoprotein transcripts expressed in human hematopoietic
      progenitors. Implications for their developmental potential towards endoderm.
AB  - Hematopoietic stem cells have been identified as multipotent cells that give rise
      to all adult hematopoietic lineages. Although the hematopoietic lineage is
      derived from the mesodermal germ layer in the embryo, recent data suggest that
      bone marrow cells with an antigenic profile consistent with that of hematopoietic
      stem cells can also differentiate to cell types of the endodermal lineages, such
      as hepatocytes. However, the molecular mechanisms associated with these events
      are entirely unknown. For decades, alpha-fetoprotein (AFP) has been used as a
      differentiation marker for endodermal cells, because it was thought that the
      transcription of AFP mRNA is tightly regulated in a developmental and tissue
      specific process. In this report we describe two new variant forms of AFP
      transcripts in human hematopoietic progenitors that are not expressed in mature
      cells. The variant AFP (vAFP) cDNA sequences isolated from a multipotent
      hematopoietic cell line, K562, revealed that the vAFP differed from the authentic
      transcript, consisting of 15 exons, by replacing exon 1 of AFP with one or two
      exons located in the 5'-untranslated region of the AFP gene. In addition to the
      K562 cell line, vAFP transcripts were detected in normal bone marrow, thymus, and
      brain but were not detected in normal spleen, intestine, liver, or the
      hepatocellular carcinoma cell line, HepG2. This suggests expression in normal
      hematopoietic progenitors. This hypothesis was confirmed by the finding that
      CD34(+)Lin(-) hematopoietic progenitor cells purified from cord blood by flow
      cytometric sorting also expressed the variant transcripts. These results suggest
      that some hematopoietic progenitors are in a state that permits them to express
      certain types of transcripts that have been considered unique to endoderm.

PMID- 12006570
TI  - Mechanism of N-terminal autoinhibition in the Arabidopsis Ca(2+)/H(+) antiporter
      CAX1.
AB  - Regulation of Ca(2+)/H(+) antiporters may be an important function in determining
      the duration and amplitude of cytosolic Ca(2+) oscillations. Previously the
      Arabidopsis Ca(2+)/H(+) transporter, CAX1 (cation exchanger 1), was identified by
      its ability to suppress yeast mutants defective in vacuolar Ca(2+) transport.
      Recently, a 36-amino acid N-terminal regulatory region on CAX1 has been
      identified that inhibits CAX1-mediated Ca(2+)/H(+) antiport. Here we show that a
      synthetic peptide designed against the CAX1 36 amino acids inhibited Ca(2+)/H(+)
      transport mediated by an N-terminal-truncated CAX1 but did not inhibit Ca(2+)
      transport by other Ca(2+)/H(+) antiporters. Ca(2+)/H(+) antiport activity
      measured from vacuolar-enriched membranes of Arabidopsis root was also inhibited
      by the CAX1 peptide. Through analyzing CAX chimeric constructs the region of
      interaction of the N-terminal regulatory region was mapped to include 7 amino
      acids (residues 56-62) within CAX1. The CAX1 N-terminal regulatory region was
      shown to physically interact with this 7-amino acid region by yeast two-hybrid
      analysis. Mutagenesis of amino acids within the N-terminal regulatory region
      implicated several residues as being essential for regulation. These findings
      describe a unique mode of antiporter autoinhibition and demonstrate the first
      detailed mechanisms for the regulation of a Ca(2+)/H(+) antiporter from any
      organism.

PMID- 12006571
TI  - Escherichia coli MoeA and MogA. Function in metal incorporation step of
      molybdenum cofactor biosynthesis.
AB  - Escherichia coli MoeA and MogA are required for molybdenum cofactor biosynthesis
      and are believed to function in the addition of molybdenum to the dithiolene of
      molybdopterin to form molybdenum cofactor. Here we show that moeA(-) and mogA(-)
      cells are able to synthesize molybdopterin, but both are deficient in molybdenum
      incorporation and, as a consequence, are deficient in the formation of
      molybdopterin-guanine dinucleotide. Human sulfite oxidase expressed in E. coli
      moeA(-) could be activated in vitro in the presence of MoeA and low
      concentrations of molybdate. Sulfite oxidase purified from the moeA(-) lysate was
      also activated, although to a lesser extent than observed in the presence of
      lysate. MogA was incapable of activating sulfite oxidase expressed in E. coli
      mogA(-). These results demonstrate that molybdenum insertion into molybdopterin
      is required for molybdopterin-guanine dinucleotide formation, and that MoeA
      facilitates molybdenum incorporation at low levels of molybdate, but MogA has an
      alternative function, possibly as a carrier for molybdopterin during molybdenum
      incorporation.

PMID- 12006572
TI  - Palmitoylation of KChIP splicing variants is required for efficient cell surface
      expression of Kv4.3 channels.
AB  - The Ca(2+)-binding proteins KChIP1-4 (KChIP3 is also known as DREAM and
      calsenilin) act as auxiliary subunits for voltage-gated K(+) channels in the Kv4
      family. Here we identify three splicing isoforms of rat KChIP2 with variable N
      terminal peptides. The two longer isoforms, which contain the 32-amino acid
      peptide, produce larger increases in Kv4.3 protein level and current density and
      more effectively localize themselves and their associated channels at the plasma
      membrane than the shortest variant. The 32-amino acid peptide contains potential
      palmitoylation cysteines. Metabolic labeling demonstrates that these cysteines in
      the KChIP2 isoforms, as well as the corresponding sites in KChIP3, are
      palmitoylated. Mutating these cysteines reduces their plasma membrane
      localization and the enhancement of Kv4.3 current density. Thus, palmitoylation
      of the KChIP auxiliary subunits controls plasma membrane localization of their
      associated channels.

PMID- 12006573
TI  - Sterol-dependent regulation of sphingolipid metabolism in Saccharomyces
      cerevisiae.
AB  - We had previously isolated the temperature-sensitive erg26-1 mutant and
      characterized the sterol defects in erg26-1 cells (Baudry, K., Swain, E., Rahier,
      A., Germann, M., Batta, A., Rondet, S., Mandala, S., Henry, K., Tint, G. S.,
      Edlind, T., Kurtz, M., and Nickels, J. T., Jr. (2001) J. Biol. Chem. 276, 12702
      12711). We have now determined the defects in sphingolipid metabolism in erg26-1
      cells, examined their effects on cell growth, and initiated studies designed to
      elucidate how might changes in sterol levels coordinately regulate sphingolipid
      metabolism in Saccharomyces cerevisiae. Using [(3)H]inositol radiolabeling
      studies, we found that the biosynthetic rate and steady-state levels of specific
      hydroxylated forms of inositolphosphorylceramides were decreased in erg26-1 cells
      when compared with wild type cells. [(3)H]Dihydrosphingosine radiolabeling
      studies demonstrated that erg26-1 cells had decreased levels of the
      phytosphingosine-derived ceramides that are the direct precursors of the specific
      hydroxylated inositol phosphorylceramides found to be lower in these cells. Gene
      dosage experiments using the sphingolipid long chain sphingoid base (LCB)
      hydroxylase gene, SUR2, suggest that erg26-1 cells may accumulate LCB, thus
      placing one point of sterol regulation of sphingolipid synthesis possibly at the
      level of ceramide metabolism. The results from additional genetic studies using
      the sphingolipid hydroxylase and copper transporter genes, SCS7 and CCC2,
      respectively, suggest a second possible point of sterol regulation at the level
      of complex sphingolipid hydroxylation. In addition, [(3)H]inositol radiolabeling
      of sterol biosynthesis inhibitor-treated wild type cells and late sterol pathway
      mutants showed that additional blocks in sterol biosynthesis have profound
      effects on sphingolipid metabolism, particularly sphingolipid hydroxylation
      state. Finally, our genetic studies in erg26-1 cells using the LCB phosphate
      phosphatase gene, LBP1, suggest that increasing the levels of the LCB sphingoid
      base phosphate can remediate the temperature-sensitive phenotype of erg26-1
      cells.

PMID- 12006574
TI  - Angiotensin IV is a potent agonist for constitutive active human AT1 receptors.
      Distinct roles of the N-and C-terminal residues of angiotensin II during AT1
      receptor activation.
AB  - The octapeptide hormone, angiotensin II (Ang II), exerts its major physiological
      effects by activating AT(1) receptors. In vivo Ang II is degraded to bioactive
      peptides, including Ang III (angiotensin-(2-8)) and Ang IV (angiotensin-(3-8)).
      These peptides stimulate inositol phosphate generation in human AT(1) receptor
      expressing CHO-K1 cells, but the potency of Ang IV is very low. Substitution of
      Asn(111) with glycine, which is known to cause constitutive receptor activation
      by disrupting its interaction with the seventh transmembrane helix (TM VII),
      selectively increased the potency of Ang IV (900-fold) and angiotensin-(4-8), and
      leads to partial agonism of angiotensin-(5-8). Consistent with the need for the
      interaction between Arg(2) of Ang II and Ang III with Asp(281), substitution of
      this residue with alanine (D281A) decreased the peptide's potency without
      affecting that of Ang IV. All effects of the D281A mutation were superseded by
      the N111G mutation. The increased affinity of Ang IV to the N111G mutant was also
      demonstrated by binding studies. A model is proposed in which the Arg(2)-Asp(281)
      interaction causes a conformational change in TM VII of the receptor, which,
      similar to the N111G mutation, eliminates the constraining intramolecular
      interaction between Asn(111) and TM VII. The receptor adopts a more relaxed
      conformation, allowing the binding of the C-terminal five residues of Ang II that
      switches this "preactivated" receptor into the fully active conformation.

PMID- 12006575
TI  - The C-terminal extension (CTE) of the nuclear hormone receptor DNA binding domain
      determines interactions and functional response to the HMGB-1/-2 co-regulatory
      proteins.
AB  - Previously, we and others reported that the high mobility group proteins, HMGB-1/
      2, enhance DNA binding in vitro and transactivation in situ by the steroid
      hormone subgroup of nuclear receptors but did not influence these functions of
      class II receptors. We show here that the DNA binding domain (DBD) is sufficient
      to account for the selective influence of HMGB-1/-2 on the steroid class of
      receptors. Furthermore, the use of chimeric DBDs reveals that this selectivity is
      dependent on the C-terminal extension (CTE), amino acid sequences adjacent to the
      zinc finger core DBD. HMGB-1/-2 interact directly with the DBDs of steroid but
      not class II receptors, and this interaction requires the CTE. This in vitro
      interaction correlates with a requirement of the CTE for maximal HMGB-1/-2
      enhancement of DNA binding in vitro and transcriptional activation in cells.
      Finally, class II receptor DBDs have a much higher intrinsic affinity for DNA
      than steroid receptor DBDs, and this affinity difference is also dependent on the
      CTE. These results reveal the importance of the steroid receptor CTE for DNA
      binding affinity and functional response to HMGB-1/-2.

PMID- 12006576
TI  - ShcB and ShcC activation by the Trk family of receptor tyrosine kinases.
AB  - Activation of the neurotrophin Trk receptors is a key process in the survival and
      development of the nervous system. The signaling adapters ShcB and ShcC, but not
      ShcA, are thought to be the primary Shc adaptor proteins in neurons as both are
      highly expressed in both the developing and adult nervous system. Although a
      previous study suggested that ShcB and ShcC do not strongly interact with the Trk
      receptors (1), we find that ShcB and ShcC bind the Trk receptors in a
      phosphotyrosine-dependent manner via their N-terminal phosphotyrosine binding
      domain at Tyr(499) (TrkA) and Tyr(515) (TrkB), they are tyrosine-phosphorylated
      in response to neurotrophin stimulation, and they enhance the activation of
      mitogen-activated protein kinase in Trk-expressing cells. Moreover, neurotrophin
      treatment of primary cortical neurons stimulates ShcB/ShcC-Trk interaction and
      the tyrosine phosphorylation of ShcB/ShcC, indicating that they are bona fide
      targets of the Trk receptors in vivo. Interestingly, two proteins (pp60 and pp75)
      co-immunoprecipitate with ShcB and ShcC in response to neurotrophin stimulation
      in primary cortical neurons, suggesting a potential role of these unknown targets
      in neurotrophin signaling. Collectively, these results demonstrate that ShcB and
      ShcC, and their co-immunoprecipitating proteins, are activated by the Trk
      receptors in primary neurons.

PMID- 12006577
TI  - Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses
      mitochondrial iron accumulation in a yeast frataxin-deficient strain.
AB  - The mitochondrial solute carriers Mrs3p and Mrs4p were originally isolated as
      multicopy suppressors of intron splicing defects. We show here that MRS4 is co
      regulated with the iron regulon genes, and up-regulated in a strain deficient for
      Yfh1p, the yeast homologue of human frataxin. Using in vivo 55Fe cell
      radiolabeling we show that in glucose-grown cells mitochondrial iron accumulation
      is 5-15 times higher in deltaYFH1 than in wild-type strain. However, although in
      a deltaYFH1deltaMRS3deltaMRS4 strain, the intracellular 55Fe content is extremely
      high, the mitochondrial iron concentration is decreased to almost wild-type
      levels. Moreover, deltaYFH1deltaMRS3deltaMRS4 cells grown in high iron media do
      not lose their mitochondrial genome. Conversely, a deltaYFH1 strain
      overexpressing MRS4 has an increased mitochondrial iron content and no
      mitochondrial genome. Therefore, MRS4 is required for mitochondrial iron
      accumulation in deltaYFH1 cells. Expression of the iron regulon and intracellular
      55Fe content are higher in a deltaMRS3deltaMRS4 strain than in the wild type.
      Nevertheless, the mitochondrial 55Fe content, a balance between iron uptake and
      exit, is decreased by a factor of two. Moreover, 55Fe incorporation into heme by
      ferrochelatase is increased in an MRS4-overexpressing strain. The function of
      MRS4 in iron import into mitochondria is discussed.

PMID- 12006578
TI  - Nitric oxide ameliorates hydrophobic bile acid-induced apoptosis in isolated rat
      hepatocytes by non-mitochondrial pathways.
AB  - Hydrophobic bile acids are toxic to isolated rat hepatocytes by mechanisms
      involving mitochondrial dysfunction and oxidative stress. In the current study we
      examined the role of nitric oxide (NO), a potential mediator of apoptosis, during
      bile acid-induced apoptosis. Freshly isolated rat hepatocytes and hepatic
      mitochondria generated NO and peroxynitrite (ONOO(-)) in a concentration- and
      time-dependent manner when exposed to the toxic bile salt glycochenodeoxycholate
      (GCDC) (25-500 microm), which was prevented by the nitric-oxide synthase (NOS)
      inhibitors N(G)-monomethyl-N-arginine monoacetate (l-NMMA) and 1400W.
      Relationships between hepatocyte NO production and apoptosis were examined by
      comparing the effects of NOS inhibitors with other inhibitors of GCDC-induced
      apoptosis. Inhibitors of caspases 8 and 9, the mitochondrial permeability
      transition blocker cyclosporin A, and the antioxidant idebenone reduced NO
      generation and apoptosis in GCDC-treated hepatocytes. In contrast, NOS inhibitors
      had no effect on GCDC-induced apoptosis despite marked reduction of NO and ONOO(
      ). However, treatment with the NO donors S-nitroso-N-acetylpenicillamine and
      spermine NONOate [N-(-aminoethyl)N-(2-hydroxy-2-nitrohydrazino)-1,2
      ethylenediamine) inhibited apoptosis and caspase 3 activity while significantly
      elevating NO levels above GCDC-stimulated levels. Neither NO donors nor NOS
      inhibitors affected GCDC-induced mitochondrial permeability transition or
      cytochrome c release from liver mitochondria or GCDC-induced mitochondrial
      depolarization from isolated hepatocytes, suggesting that NO inhibits bile acid
      induced hepatocyte apoptosis by a non-mitochondrial-dependent pathway. In
      conclusion, whereas NO produced from GCDC-treated hepatocytes neither mediates
      nor protects against bile acid-induced apoptosis, higher levels of NO inhibit
      GCDC-induced hepatocyte apoptosis by caspase-dependent pathways.

PMID- 12006579
TI  - Marked perinatal lethality and cellular signaling deficits in mice null for the
      two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and
      S1P(3)/LP(B3)/EDG-3.
AB  - Five cognate G protein-coupled receptors (S1P(1-5)) have been shown to mediate
      various cellular effects of sphingosine 1-phosphate (S1P). Here we report the
      generation of mice null for S1P(2) and for both S1P(2) and S1P(3). S1P(2)-null
      mice were viable and fertile and developed normally. The litter sizes from
      S1P(2)S1P(3) double-null crosses were remarkably reduced compared with controls,
      and double-null pups often did not survive through infancy, although double-null
      survivors lacked any obvious phenotype. Mouse embryonic fibroblasts (MEFs) were
      examined for the effects of receptor deletions on S1P signaling pathways. Wild
      type MEFs were responsive to S1P in activation of Rho and phospholipase C (PLC),
      intracellular calcium mobilization, and inhibition of forskolin-activated
      adenylyl cyclase. S1P(2)-null MEFs showed a significant decrease in Rho
      activation, but no effect on PLC activation, calcium mobilization, or adenylyl
      cyclase inhibition. Double-null MEFs displayed a complete loss of Rho activation
      and a significant decrease in PLC activation and calcium mobilization, with no
      effect on adenylyl cyclase inhibition. These data extend our previous findings on
      S1P(3)-null mice and indicate preferential coupling of the S1P(2) and S1P(3)
      receptors to Rho and PLC/Ca(2+) pathways, respectively. Although either receptor
      subtype supports embryonic development, deletion of both produces marked
      perinatal lethality, demonstrating an essential role for combined S1P signaling
      by these receptors.

PMID- 12006580
TI  - Distinct phosphorylation events regulate p130- and p107-mediated repression of
      E2F-4.
AB  - The "pocket proteins" pRb (retinoblastoma tumor suppressor protein), p107, and
      p130 regulate cell proliferation via phosphorylation-sensitive interactions with
      E2F transcription factors and other proteins. We previously identified 22 in vivo
      phosphorylation sites in human p130, including three sites selectively targeted
      by cyclin D-Cdk4(6) kinases. Here we assessed the effects of alanine substitution
      at the individual or combined Cdk4(6)-specific sites in p130, compared with
      homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the
      triple p107(DeltaCdk4)* mutant strongly inhibited E2F-4 activity and imposed a
      G(1) arrest resistant to cyclin D1 coexpression. In contrast, the p130(DeltaCdk4)
      mutant still responded to cyclin D1, suggesting the existence of additional
      phosphorylation sites critical for E2F-4 regulation. Extensive mutagenesis,
      sensitive E2F reporter assays, and cell cycle analyses allowed the identification
      of six such residues (serines 413, 639, 662, 1044, 1080, and 1112) that, in
      addition to the Cdk4-specific sites, are necessary and sufficient for the
      regulation of E2F-4 and the cell cycle by p130. Surprisingly, 12 of the in vivo
      phosphorylation sites seem dispensable for E2F regulation and probably modulate
      other functions of p130. These results further elucidate the complex regulation
      of p130 and provide a molecular mechanism to explain the differential control of
      p107 and p130 by cyclin-dependent kinases.

PMID- 12006581
TI  - How do short neurotoxins bind to a muscular-type nicotinic acetylcholine
      receptor?
AB  - We investigated the interacting surface between a short curarimimetic toxin and a
      muscular-type nicotinic acetylcholine receptor, looking for the ability of
      various biotinylated Naja nigricollis alpha-neurotoxin analogues to bind
      simultaneously the receptor and streptavidin. All these derivatives, modified at
      positions 10 (loop I), 27, 30, 33, 35 (loop II), 46, and 47 (loop III) or the N
      terminal (erabutoxin numbering), still shared high affinity for the receptor, and
      in the absence of receptor they all bound soluble streptavidin. However, the
      proportion of the toxin-receptor complex that bound to streptavidin-coated beads,
      varied both with the location of the modification and with the length of the
      linker between biotin and the toxin. In the receptor-toxin complex, the concave
      side of loops II and III was not accessible to streptavidin, unlike the N
      terminus of the toxin and, to a certain extent, loop I. On the convex face, loop
      III was the most accessible, whereas the tip of loop II, especially Arg-30,
      seemed to be closer to the receptor. The present data demonstrate that short
      toxins neither penetrate deeply into a crevice as proposed earlier nor lie
      parallel to the receptor extracellular wall. These data also suggest that they
      may not lie strictly perpendicular to the cylindrical wall of the receptor. These
      results fit nicely with three-dimensional models of interaction between long
      neurotoxins and their receptors and support the idea that short and long
      curarimimetic toxins share a similar overall topology of interaction when bound
      to nicotinic receptors.

PMID- 12006582
TI  - Mechanism by which fatty acids inhibit insulin activation of insulin receptor
      substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle.
AB  - Recent studies have demonstrated that fatty acids induce insulin resistance in
      skeletal muscle by blocking insulin activation of insulin receptor substrate-1
      (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the
      mechanism by which fatty acids mediate this effect, rats were infused with either
      a lipid emulsion (consisting mostly of 18:2 fatty acids) or glycerol.
      Intracellular C18:2 CoA increased in a time-dependent fashion, reaching an
      approximately 6-fold elevation by 5 h, whereas there was no change in the
      concentration of any other fatty acyl-CoAs. Diacylglycerol (DAG) also increased
      transiently after 3-4 h of lipid infusion. In contrast there was no increase in
      intracellular ceramide or triglyceride concentrations during the lipid infusion.
      Increases in intracellular C18:2 CoA and DAG concentration were associated with
      protein kinase C (PKC)-theta activation and a reduction in both insulin
      stimulated IRS-1 tyrosine phosphorylation and IRS-1 associated PI3-kinase
      activity, which were associated with an increase in IRS-1 Ser(307)
      phosphorylation. These data support the hypothesis that an increase in plasma
      fatty acid concentration results in an increase in intracellular fatty acyl-CoA
      and DAG concentrations, which results in activation of PKC-theta leading to
      increased IRS-1 Ser(307) phosphorylation. This in turn leads to decreased IRS-1
      tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase
      activity resulting in decreased insulin-stimulated glucose transport activity.

PMID- 12006583
TI  - Functional and molecular characterization of nucleobase transport by recombinant
      human and rat equilibrative nucleoside transporters 1 and 2. Chimeric constructs
      reveal a role for the ENT2 helix 5-6 region in nucleobase translocation.
AB  - The human (h) and rat (r) equilibrative (Na(+)-independent) nucleoside
      transporters (ENTs) hENT1, rENT1, hENT2, and rENT2 belong to a family of integral
      membrane proteins with 11 transmembrane domains (TMs) and are distinguished
      functionally by differences in sensitivity to inhibition by
      nitrobenzylthioinosine and coronary vasoactive drugs. Structurally, the proteins
      have a large glycosylated loop between TMs 1 and 2 and a large cytoplasmic loop
      between TMs 6 and 7. In the present study, hENT1, rENT1, hENT2, and rENT2 were
      produced in Xenopus laevis oocytes and investigated for their ability to
      transport pyrimidine and purine nucleobases. hENT2 and rENT2 efficiently
      transported radiolabeled hypoxanthine, adenine, guanine, uracil, and thymine
      (apparent K(m) values 0.7-2.6 mm), and hENT2, but not rENT2, also transported
      cytosine. These findings were independently confirmed by hypoxanthine transport
      experiments with recombinant hENT2 produced in purine-cytosine permease (FCY2)
      deficient Saccharomyces cerevisiae and provide the first direct demonstration
      that the ENT2 isoform is a dual mechanism for the cellular uptake of nucleosides
      and nucleobases, both of which are physiologically important salvage metabolites.
      In contrast, recombinant hENT1 and rENT1 mediated negligible oocyte fluxes of
      hypoxanthine relative to hENT2 and rENT2. Chimeric experiments between rENT1 and
      rENT2 using splice sites at rENT1 residues 99 (end of TM 2), 171 (between TMs 4
      and 5), and 231 (end of TM 6) identified TMs 5-6 of rENT2 (amino acid residues
      172-231) as a determinant of nucleobase transport activity, suggesting that this
      domain forms part(s) of the ENT2 substrate translocation channel.

PMID- 12006584
TI  - Regulation of glycolytic flux in ischemic preconditioning. A study employing
      metabolic control analysis.
AB  - Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in
      ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation
      contributes to myocardial protection. However, precise mechanisms of glycolytic
      flux and its regulation in IP remain to be elucidated. In open chest pigs, IP was
      achieved by two cycles of 10-min coronary artery occlusion and 30-min reperfusion
      prior to a 45-min index ischemia and 120-min reperfusion. Myocardial contents in
      glycolytic intermediates were assessed by high performance liquid chromatographic
      analysis of serial myocardial biopsies under control conditions and IP. Detailed
      time courses of metabolite contents allow an in-depth description of EMP
      regulation during index ischemia using metabolic control analysis. IP reduced
      myocardial infarct size (control, 90.0 +/- 3.1 versus 5.05 +/- 2.1%; p < 0.001)
      and attenuated myocardial lactate accumulation (end-ischemic contents, 31.9 +/-
      4.47 versus 10.3 +/- 1.26 micromol/wet weight, p < 0.0001), whereby a decrease in
      anaerobic glycolytic flux by at least 70% could constantly be observed throughout
      index ischemia. By calculation of flux:metabolite co-responses, the mechanisms of
      glycolytic regulation were investigated. The continuous deceleration of EMP flux
      in control myocadium could neither be explained on the basis of substrate
      availability nor be attributed to regulatory "key enzymes," as multisite
      regulation was employed for flux adjustment. In myocardium subjected to IP, an
      even pronounced deceleration of EMP flux during index ischemia was observed.
      Again, the adjustment of EMP flux was because of multisite modulation without any
      evidence for flux limitation by substrate availability or a key enzyme. However,
      IP changed the regulatory properties of most EMP enzymes, and some of these
      patterns could not be explained on the basis of substrate kinetics. Instead,
      other regulatory mechanisms, which have previously not yet been described for EMP
      enzymes, must be considered. These altered biochemical properties of the EMP
      enzymes have not yet been described.

PMID- 12006585
TI  - Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer.
AB  - CDC6 plays a critical role in regulation of the onset of DNA replication in
      eukaryotic cells. We have found that Cdc6 expression is down-regulated in
      prostate cancer as detected by semiquantitative reverse transcriptase-PCR of
      prostate cell lines and laser-captured microdissected prostate tissues. This
      result was substantiated by immunohistochemical analysis of paraffin-embedded
      tissue sections and immunoblot analysis of benign (BPH-1) and adenocarcinomatous
      prostatic cells. Furthermore, a 100-fold reduction in the transcription
      efficiency of the Cdc6 promoter-luciferase construct was noted in the metastatic
      PC3 cells compared with that in BPH-1 cells. Concentration of the E2F and Oct1
      transcription factors that have putative binding sites in the Cdc6 promoter was
      substantially low in PC3 cells compared with BPH cells. Mutagenesis of the two
      E2F binding sites on the Cdc6 promoter resulted in increased promoter activity in
      PC3 cells owing to elimination of the negative regulation by pRb.E2F complex but
      not to the level of that obtained in BPH cells. We conclude that an altered
      interaction of transcription factors may be responsible for the down-regulation
      of Cdc6 transcription in PC3 cells. Our study suggests a potential use of the
      lack of CDC6 expression as an index of prostate cancer development.

PMID- 12006586
TI  - In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel
      serine kinase in insulin-resistant rodents.
AB  - Insulin resistance is a key pathophysiologic feature of obesity and type 2
      diabetes and is associated with other human diseases, including atherosclerosis,
      hypertension, hyperlipidemia, and polycystic ovarian disease. Yet, the specific
      cellular defects that cause insulin resistance are not precisely known. Insulin
      receptor substrate (IRS) proteins are important signaling molecules that mediate
      insulin action in insulin-sensitive cells. Recently, serine phosphorylation of
      IRS proteins has been implicated in attenuating insulin signaling and is thought
      to be a potential mechanism for insulin resistance. However, in vivo increased
      serine phosphorylation of IRS proteins in insulin-resistant animal models has not
      been reported before. In the present study, we have confirmed previous findings
      in both JCR:LA-cp and Zucker fatty rats, two genetically unrelated insulin
      resistant rodent models, that an enhanced serine kinase activity in liver is
      associated with insulin resistance. The enhanced serine kinase specifically
      phosphorylates the conserved Ser(789) residue in IRS-1, which is in a sequence
      motif separate from the ones for MAPK, c-Jun N-terminal kinase, glycogen-synthase
      kinase 3 (GSK-3), Akt, phosphatidylinositol 3'-kinase, or casein kinase. It is
      similar to the phosphorylation motif for AMP-activated protein kinase, but the
      serine kinase in the insulin-resistant animals was shown not to be an AMP
      activated protein kinase, suggesting a potential novel serine kinase. Using a
      specific antibody against Ser(P)(789) peptide of IRS-1, we then demonstrated for
      the first time a striking increase of Ser(789)-phosphorylated IRS-1 in livers of
      insulin-resistant rodent models, indicating enhanced serine kinase activity in
      vivo. Taken together, these data strongly suggest that unknown serine kinase
      activity and Ser(789) phosphorylation of IRS-1 may play an important role in
      attenuating insulin signaling in insulin-resistant animal models.

PMID- 12006587
TI  - Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent
      tetrodotoxin-sensitive sodium channels.
AB  - Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels
      (VSSCs). Synthetic forms of mu-conotoxins PIIIA and PIIIA-(2-22) were found to
      inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little effect on TTX
      resistant VSSC current in sensory ganglion neurons. In rat brain neurons, these
      peptides preferentially inhibited the persistent over the transient VSSC current.
      Radioligand binding assays revealed that PIIIA, PIIIA-(2-22), and mu-conotoxins
      GIIIB discriminated among TTX-sensitive VSSCs in rat brain, that these and GIIIC
      discriminated among the corresponding VSSCs in human brain, and GIIIA had low
      affinity for neuronal VSSCs. (1)H NMR studies found that PIIIA adopts two
      conformations in solution due to cis/trans isomerization at hydroxyproline 8. The
      major trans conformation results in a three-dimensional structure that is
      significantly different from the previously identified conformation of mu
      conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs.
      Comparison of the structures and activity of PIIIA to muscle-selective mu
      conotoxins provides an insight into the structural requirements for inhibition of
      different TTX-sensitive sodium channels by mu-conotoxins.

PMID- 12006588
TI  - The lipid peroxidation product 4-hydroxynonenal facilitates opening of voltage
      dependent Ca2+ channels in neurons by increasing protein tyrosine
      phosphorylation.
AB  - Calcium influx through voltage-dependent calcium channels (VDCCs) mediates a
      variety of functions in neurons and other excitable cells, but excessive calcium
      influx through these channels can contribute to neuronal death in pathological
      settings. Oxyradical production and membrane lipid peroxidation occur in neurons
      in response to normal activity in neuronal circuits, whereas excessive lipid
      peroxidation is implicated in the pathogenesis of of neurodegenerative disorders.
      We now report on a specific mechanism whereby lipid peroxidation can modulate the
      activity of VDCCs. The lipid peroxidation product 4-hydroxy-2,3-nonenal (4HN)
      enhances dihydropyridine-sensitive whole-cell Ca2+ currents and increases
      depolarization-induced increases of intracellular Ca2+ levels in hippocampal
      neurons. Prolonged exposure to 4HN results in neuronal death, which is prevented
      by treatment with glutathione and attenuated by the L-type Ca2+ channel blocker
      nimodipine. Tyrosine phosphorylation of alpha1 VDCC subunits is increased in
      neurons exposed to 4HN, and studies using inhibitors of tyrosine kinases and
      phosphatases indicate a requirement for tyrosine phosphorylation in the
      enhancement of VDCC activity in response to 4HN. Phosphorylation-mediated
      modulation of Ca2+ channel activity in response to lipid peroxidation may play
      important roles in the responses of neurons to oxidative stress in both
      physiological and pathological settings.

PMID- 12006589
TI  - Use of an in vivo reporter assay to test for transcriptional and translational
      fidelity in yeast.
AB  - Eukaryotic RNA polymerase II and Escherichia coli RNA polymerase possess an
      intrinsic ribonuclease activity that is stimulated by the polymerase-binding
      proteins SII and GreB, respectively. This factor-activated hydrolysis of nascent
      RNA has been postulated to be involved in transcription elongation as well as
      removal of incorrect bases misincorporated into RNA. Little is known about the
      frequency of misincorporation by RNA polymerases in vivo or about the mechanisms
      involved in improving RNA polymerase accuracy. Here we have developed a
      luciferase reporter system in an effort to assay for base misincorporation in
      living Saccharomyces cerevisiae. The assay employs a luciferase open reading
      frame that contains a premature stop codon. The inactive truncated enzyme would
      become active if misincorporation by RNA polymerase II took place at the stop
      triplet. Yeast lacking SII did not display a significant change in reporter
      activity when compared with wild-type cells. We estimate that under our assay
      conditions, mRNAs with a misincorporation at the test site could not exceed 1
      transcript per 500 cells. The reporter assay was very effective in detecting the
      previously described process of nonsense suppression (translational read-through)
      by ribosomes, making it difficult to determine an absolute level of basal (SII
      independent) misincorporation by RNA polymerase II. Although these data cannot
      exclude the possibility that SII is involved in proofreading, they make it
      unlikely that such a contribution is physiologically significant, especially
      relative to the high frequency of translational errors.

PMID- 12006590
TI  - Inhibition of plasmodium falciparum triose-phosphate isomerase by chemical
      modification of an interface cysteine. Electrospray ionization mass spectrometric
      analysis of differential cysteine reactivities.
AB  - Plasmodium falciparum triose-phosphate isomerase, a homodimeric enzyme, contains
      four cysteine residues at positions 13, 126, 196, and 217 per subunit. Among
      these, Cys-13 is present at the dimer interface and is replaced by methionine in
      the corresponding human enzyme. We have investigated the effect of sulfhydryl
      labeling on the parasite enzyme, with a view toward developing selective covalent
      inhibitors by targeting the interface cysteine residue. Differential labeling of
      the cysteine residues by iodoacetic acid and iodoacetamide has been followed by
      electrospray ionization mass spectrometry and positions of the labels determined
      by analysis of tryptic fragments. The rates of labeling follows the order Cys-196
      > Cys-13 Cys-217/Cys-126, which correlates well with surface accessibility
      calculations based on the enzyme crystal structure. Iodoacetic acid labeling
      leads to a soluble, largely inactive enzyme, whereas IAM labeling leads to
      precipitation. Carboxyl methylation of Cys-13 results in formation of monomeric
      species detectable by gel filtration. Studies with an engineered C13D mutant
      permitted elucidation of the effects of introducing a negative charge at the
      interface. The C13D mutant exhibits a reduced stability to denaturants and 7-fold
      reduction in the enzymatic activity even under the concentrations in which
      dimeric species are observed.

PMID- 12006591
TI  - Alternative splicing and promoter usage generates an intracellular stromelysin 3
      isoform directly translated as an active matrix metalloproteinase.
AB  - Human stromelysin 3 (ST3) is a matrix metalloproteinase (MMP) that has been
      implicated in cancer progression and in various tissue remodeling processes.
      Unlike most MMPs, ST3 is characterized by a distinct substrate specificity and a
      specific regulation and is not directly involved in extracellular matrix
      degradation. In the present study, we have identified an additional ST3 gene
      promoter that is accessible to nuclear factors such as C/EBP and retinoic acid
      receptors. This human specific promoter is inducible and controls the expression
      of a novel ST3 transcript called the beta-ST3 that is expressed in cultured cells
      and in placenta. This transcript encodes a 40-kDa ST3 isoform that lacks both the
      signal peptide common to all secreted MMPs and the prodomain that normally
      maintains enzyme latency. Consistent with the lack of a signal peptide, the beta
      ST3 was found to be intracellular. The relative amount of the extracellular alpha
      ST3 isoform was about 20-fold higher than that of the intracellular ST3 isoforms,
      as estimated by Western blot analysis. Furthermore, recombinant beta-ST3 produced
      in Escherichia coli exhibits a proteolytic activity against alpha1-proteinase
      inhibitor, a substrate previously shown to be inactivated by the alpha-ST3.
      Therefore, although it was thought that all MMPs were synthesized as inactive
      zymogens and functioned extracellularly, this is the first MMP isoform reported
      that is generated by alternative promoter usage and directly translated as an
      active enzyme. Although the intracellular function of the beta-ST3 remains to be
      investigated, these data support the idea that the functions of MMPs are not
      restricted to the extracellular space.

PMID- 12006592
TI  - Novel isoform of insulin receptor substrate p53/p58 is generated by alternative
      splicing in the CRIB/SH3-binding region.
AB  - Insulin receptor substrate p53/p58 (IRSp53) is involved in cytoskeletal dynamics
      and is a candidate disease sensor in polyglutamine expansion neurodegeneration.
      It is widely expressed throughout the body, but its levels are dramatically
      elevated in forebrain regions. IRSp53 functions as a signal transducing adaptor
      between activated Rho family GTPases and their effectors. There are four known
      alternatively spliced isoforms of IRSp53 that vary by the identity of the 3'
      terminal exon. We report here that there is a fifth alternatively spliced
      isoform, IRSp53-B, which lacks 40 amino acids abutting the CRIB/SH3 (Cdc42/Rac
      interactive binding/Src homology 3)-binding site. We speculate that the novel
      form has an altered function related to the mechanism of autoinactivation. IRSp53
      B has an odd history in the mammalian lineage, which may complicate the use of
      rodent models to study cytoskeletal reorganization.

PMID- 12006593
TI  - Functional synergy of actin filament cross-linking proteins.
AB  - The organization of filamentous actin (F-actin) in resilient networks is
      coordinated by various F-actin cross-linking proteins. The relative tolerance of
      cells to null mutations of genes that code for a single actin cross-linking
      protein suggests that the functions of those proteins are highly redundant. This
      apparent functional redundancy may, however, reflect the limited resolution of
      available assays in assessing the mechanical role of F-actin cross
      linking/bundling proteins. Using reconstituted F-actin networks and rheological
      methods, we demonstrate how alpha-actinin and fascin, two F-actin cross
      linking/bundling proteins that co-localize along stress fibers and in
      lamellipodia, could synergistically enhance the resilience of F-actin networks in
      vitro. These two proteins can generate microfilament arrays that "yield" at a
      strain amplitude that is much larger than each one of the proteins separately. F
      actin/alpha-actinin/fascin networks display strain-induced hardening, whereby the
      network "stiffens" under shear deformations, a phenomenon that is non-existent in
      F-actin/fascin networks and much weaker in F-actin/alpha-actinin networks. Strain
      hardening is further enhanced at high rates of deformation and high
      concentrations of actin cross-linking proteins. A simplified model suggests that
      the optimum results of the competition between the increased stiffness of bundles
      and their decreased density of cross-links. Our studies support a re-evaluation
      of the notion of functional redundancy among cytoskeletal regulatory proteins.

PMID- 12006594
TI  - Synaptotagmin V is targeted to dense-core vesicles that undergo calcium-dependent
      exocytosis in PC12 cells.
AB  - Synaptotagmins (Syts) III, V, VI, and X are classified as a subclass of Syt,
      based on their sequence similarities and biochemical properties (Ibata, K.,
      Fukuda, M., and Mikoshiba, K. (1998) J. Biol. Chem. 273, 12267-12273; Fukuda, M.,
      Kanno, E., and Mikoshiba, K. (1999) J. Biol. Chem. 274, 31421-31427). Although
      they have been suggested to be involved in vesicular trafficking, as in the role
      of the Syt I isoform in synaptic vesicle exocytosis, their exact functions remain
      to be clarified, and even their precise subcellular localization is still a
      matter of controversy. In this study, we established rat pheochromocytoma (PC12)
      cell lines that stably express Syts III-, V-, VI-, and X-GFP (green fluorescence
      protein) fusion proteins, respectively, to determine their precise subcellular
      localizations. Surprisingly, Syts III-, V-, VI-, and X-GFP proteins were found to
      be targeted to specific organelles: Syt III-GFP to near the plasma membrane, Syt
      V-GFP to dense-core vesicles, Syt VI-GFP to endoplasmic reticulum-like
      structures, and Syt X-GFP to vesicles (other than dense-core vesicles) present in
      cytoplasm. We showed that Syt V-containing vesicles at the neurites of PC12 cells
      were processed to exocytosis in a Ca2+-dependent manner. Immunohistochemical
      analysis further showed that endogenous Syt V was also localized on dense-core
      vesicles in the mouse brain and specifically expressed in glucagon-positive alpha
      cells in mouse pancreatic islets, but not in beta- or delta-cells. Based on these
      results, we propose that Syt V is a dense-core vesicle-specific Syt isoform that
      controls a specific type of Ca2+-regulated secretion.

PMID- 12006595
TI  - Cloning and characterization of a leucyl aminopeptidase from three pathogenic
      Leishmania species.
AB  - Aminopeptidases are emerging as exciting novel drug targets and vaccine
      candidates in parasitic infections. In this study, we describe for the first time
      an aminopeptidase from three highly pathogenic Leishmania species. Intronless
      genes encoding a leucyl aminopeptidase (lap) were cloned from Leishmania
      amazonensis, Leishmania donovani, and Leishmania major, which encoded 60-kDa
      proteins that displayed homology to leucyl aminopeptidases from Gram-negative
      bacteria, plants, and mammals. The lap genes were present as a single copy in
      each genome, and lap mRNA was detected by reverse transcription-PCR in all life
      cycle stages of L. amazonensis. Lap assembled into catalytically competent 360
      kDa hexamers and demonstrated potent amidolytic activity against synthetic
      aminopeptidase substrates containing leucine, methionine, and cysteine residues,
      representing the most restricted substrate specificity of any leucyl
      aminopeptidase described to date. Optimal activity was observed against L-leucyl
      7-amido-4-methylcoumarin (k(cat)/K(m) approximately 63 s(-1) x mm(-1)) with a pH
      optimum of 8.5. Leishmania Lap activity was inhibited by metal ion chelators and
      enhanced by divalent manganese, cobalt, and nickel cations, although only zinc
      was detected in the purified Lap by inductively coupled plasma atomic emission
      spectroscopy, indicating that zinc is the natural Lap cofactor. Activity was
      potently inhibited by bestatin and apstatin in a slow binding competitive
      fashion, with K(i)* values of 3 and 44 nm, respectively. Actinonin was a tight
      binding competitive inhibitor (K(i) approximately 1 nm), whereas arphamenine A
      (K(i) approximately 70 microm) and L-leucinol (K(i) approximately 100 microm)
      were non-tight binding competitive inhibitors. Lap was not secreted by Leishmania
      in vitro and was localized to the parasite cytosol.

PMID- 12006596
TI  - Specific binding of RGS9-Gbeta 5L to protein anchor in photoreceptor membranes
      greatly enhances its catalytic activity.
AB  - The complex between the short splice variant of the ninth member of the RGS
      protein family and the long splice variant of type 5 G protein beta subunit (RGS9
      Gbeta5L) plays a critical role in regulating the duration of the light response
      in vertebrate photoreceptors by activating the GTPase activity of the
      photoreceptor-specific G protein, transducin. RGS9-Gbeta5L is tightly associated
      with the membranes of photoreceptor outer segments; however, the nature of this
      association remains unknown. Here we demonstrate that rod outer segment membranes
      contain a limited number of sites for high affinity RGS9-Gbeta5L binding, which
      are highly sensitive to proteolysis. In membranes isolated from bovine rod outer
      segments, all of these sites are occupied by the endogenous RGS9-Gbeta5L, which
      prevents the binding of exogenous recombinant RGS9-Gbeta5L to these sites.
      However, treating membranes with urea or high pH buffers causes either removal or
      denaturation of the endogenous RGS9-Gbeta5L, allowing for high affinity binding
      of recombinant RGS9-Gbeta5L to these sites. This binding results in a striking
      approximately 70-fold increase in the RGS9-Gbeta5L ability to activate transducin
      GTPase. The DEP (disheveled/EGL-10/pleckstrin) domain of RGS9 plays a crucial
      role in the RGS9-Gbeta5L membrane attachment, as evident from the analysis of
      membrane-binding properties of deletion mutants lacking either N- or C-terminal
      parts of the RGS9 molecule. Our data indicate that specific association of RGS9
      Gbeta5L with photoreceptor disc membranes serves not only as a means of targeting
      it to an appropriate subcellular compartment but also serves as an important
      determinant of its catalytic activity.

PMID- 12006597
TI  - Regulation of mRNA expression in macrophages after Yersinia enterocolitica
      infection. Role of different Yop effectors.
AB  - The Yop virulon, which comprises a complete type III secretion system and
      secreted proteins, allows bacteria from the genus Yersinia to resist the
      nonspecific immune response of the host. This virulon, which is encoded by a
      plasmid called pYV in Yersinia enterocolitica, enables extracellular bacteria to
      inject six Yop effectors (YopE, -H, -T, -O, -P, -M) into the host cell. To
      investigate the role of YopP, YopM, and the other pYV-encoded factors on the
      expression of the host cell genes, we characterized the transcriptome alterations
      in infected mouse macrophages using the microarray technique. PU5-1.8 macrophages
      were infected either with an avirulent (pYV(-)), a wild type (pYV(+)), or two
      knockout (yopP(-) and yopM(-)) mutants of Y. enterocolitica. Expression
      alterations in response to Y. enterocolitica infection were monitored for 6657
      genes. Among those, 857 genes were affected, 339 of which were specifically
      regulated by the action of the Yop virulon. Further analysis of those 339 genes
      allowed identification of specific targets of YopP, YopM, or the other pYV
      encoded factors. According to these results, the main action of the Yop virulon
      is to counteract the host cell pro-inflammatory response to the infection. YopP
      participates to this inhibition, whereas another pYV-encoded factor appears to
      also be involved in this down-regulation. Besides, YopM was found to induce the
      regulation of genes involved in cell cycle and cell growth, revealing for the
      first time an in vitro effect for YopM. In addition to YopM, other pYV factors
      distinct from YopP affected the expression of genes involved in cycling. In
      conclusion, these results provide new insight into the mechanisms of Yersinia
      pathogenicity by identifying the changes in host genes expression after infection
      and highlight the concerted actions of the different Yop effectors.

PMID- 12006598
TI  - Annexin XXI (ANX21) of Giardia lamblia has sequence motifs uniquely sdhared by
      giardial annexins and is specifically localized in the flagella.
AB  - We have identified a novel annexin, ANX21, in trophozoites of Giardia lamblia.
      The nucleotide sequence encoding this protein deviated from a published sequence
      in predicting an additional endonexin fold in the fourth annexin domain. In
      addition, several motifs exclusively shared by other annexins of G. lamblia in
      their predicted fourth repeat and predicted to be localized on the opposite
      (concave) surface of the molecule became apparent. Western blots of trophozoite
      fractions probed with antiserum against the recombinant protein indicated that
      this annexin, like the other giardial annexins ANX19 and ANX20, associates with
      phospholipids in the presence of Ca(2+). Finally, confocal laser scanning of
      trophozoites showed that the protein, apart from the median body, was exclusively
      localized in the eight flagella. Together, these data suggest that ANX21 may
      function as a Ca(2+)-regulated structural element linking phospholipid bilayer
      and underlying axoneme.

PMID- 12006599
TI  - The function of the [4Fe-4S] clusters and FAD in bacterial and archaeal
      adenylylsulfate reductases. Evidence for flavin-catalyzed reduction of adenosine
      5'-phosphosulfate.
AB  - The iron-sulfur flavoenzyme adenylylsulfate (adenosine 5'-phosphosulfate, APS)
      reductase catalyzes reversibly the 2-electron reduction of APS to sulfite and
      AMP, a key step in the biological sulfur cycle. APS reductase from one archaea
      and three different bacteria has been purified, and the molecular and catalytic
      properties have been characterized. The EPR parameters and redox potentials (-60
      and -520 mV versus NHE) have been assigned to the two [4Fe-4S] clusters I and II
      observed in the three-dimensional structure of the enzyme from Archaeoglobus
      fulgidus (Fritz, G., Roth, A., Schiffer, A., Buchert, T., Bourenkov, G.,
      Bartunik, H. D., Huber, H., Stetter, K. O., Kroneck, P. M. H., and Ermler, U.
      (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 1836-1841). Sulfite binds to FAD to
      form a covalent FAD N(5)-sulfite adduct with characteristic UV/visible spectra,
      in accordance with the three-dimensional structure of crystalline enzyme soaked
      with APS. UV/visible monitored titrations reveal that the substrates AMP and APS
      dock closely to the FAD cofactor. These results clearly document that FAD is the
      site of the 2-electron reduction of APS to sulfite and AMP. Reaction of APS
      reductase enzyme with sulfite and AMP leads to partial reduction of the [4Fe-4S]
      centers and formation of the anionic FAD semiquinone. Thus, both [4Fe-4S]
      clusters function in electron transfer and guide two single electrons from the
      protein surface to the FAD catalytic site.

PMID- 12006600
TI  - Intracellular activation of human adamalysin 19/disintegrin and metalloproteinase
      19 by furin occurs via one of the two consecutive recognition sites.
AB  - Adamalysin 19 (a disintegrin and metalloproteinase 19, ADAM19, or meltrin beta)
      is a plasma membrane metalloproteinase. Human ADAM19 zymogen contains two
      potential furin recognition sites (RX(K/R)R), (196)KRPR(200)R and
      (199)RRMK(203)R, between its pro- and catalytic domains. Protein N-terminal
      sequencing revealed that the cellular mature forms of hADAM19 started at
      (204)EDLNSMK, demonstrating that the preferred furin cleavage site was the
      (200)RMK(203)R downward arrow(204)EDLN. Those mature forms were catalytically
      active. Both Pittsburgh mutant of alpha(1)-proteinase inhibitor and dec-Arg-Val
      Lys-Arg-chloromethyl ketone, two specific furin inhibitors, blocked the
      activation of hADAM19. Activation of hADAM19 was also blocked by brefeldin A,
      which inhibits protein trafficking from the endoplasmic reticulum to the Golgi,
      or, a calcium ionophore known to inhibit the autoactivation of furin. When
      (202)KR were mutated to AA, the proenzyme was also activated, suggesting that
      (197)RPRR is an alternative activation site. Furthermore, only pro-forms of
      hADAM19 were detected in the (199)RR to AA mutant, which abolished both furin
      recognition sites. Moreover, the zymogens were not converted into their active
      forms in two furin-deficient mammalian cell lines; co-expression of hADAM19 and
      furin in these two cell lines restored zymogen activation. Finally, co
      localization between furin and hADAM19 was identified in the endoplasmic
      reticulum-Golgi complex and/or the trans-Golgi network. This report is the first
      thorough investigation of the intracellular activation of adamalysin 19,
      demonstrating that furin activated pro-hADAM19 in the secretory pathway via one
      of the two consecutive furin recognition sites.

PMID- 12006601
TI  - Manipulating monomer-dimer equilibrium of bovine Beta -lactoglobulin by amino
      acid substitution.
AB  - Bovine beta-lactoglobulin, a major protein in cow's milk composed of nine beta
      strands (betaA-betaI) and one alpha-helix, exists as a dimer at neutral pH while
      it dissociates to a native monomer below pH 3.0. It is assumed that the
      intermolecular beta-sheet formed between I-strands and salt bridges at AB-loops
      play important roles in dimer formation. Several site-directed mutants in which
      intermolecular interactions stabilizing the dimer would be removed were expressed
      in the methylotrophic yeast Pichia pastoris, and their monomer-dimer equilibria
      were studied by analytical ultracentrifugation. Various I-strand mutants showed
      decreases in K(a), suggesting that the intermolecular beta-sheet is essential for
      dimer formation. By substituting either Asp(33) or Arg(40) on the AB-loop to
      oppositely charged residues (i.e. R40D, R40E, and D33R), a large decrease in K(a)
      was observed probably because of the charge repulsion, which is consistent with
      the role of electrostatic attraction between Arg(40) on one monomer and Asp(33)
      on the other monomer in the wild-type dimer. However, when two of these mutants,
      R40D and D33R, were mixed, a heterodimer was formed by the electrostatic
      attraction between Arg(33) and Asp(40) of different molecules. These results
      suggested that protein-protein interactions of bovine beta-lactoglobulin can be
      manipulated by redesigning the residues on the interface without affecting global
      folding.

PMID- 12006602
TI  - Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen
      activated protein kinase activation in rat vascular smooth muscle cells.
AB  - Regulators of G protein signaling (RGS) proteins compose a highly diverse protein
      family best known for inhibition of G protein signaling by enhancing GTP
      hydrolysis by Galpha subunits. Little is known about the function of endogenous
      RGS proteins. In this study, we used synthetic ribozymes targeted to RGS2, RGS3,
      RGS5, and RGS7 to assess their function. After demonstrating the specificity of
      in vitro cleavage by the RGS ribozymes, rat aorta smooth muscle cells were used
      for transient transfection with the RGS-specific ribozymes. RGS3 and RGS5
      ribozymes differentially enhanced carbachol- and angiotensin II-induced MAP
      kinase activity, respectively, whereas RGS2 and RGS7 ribozymes had no effect.
      This enhancement was pertussis toxin-insensitive. Thus RGS3 is a negative
      modulator of muscarinic m3 receptor signaling, and RGS5 is a negative modulator
      of angiotensin AT1a receptor signaling through G(q/11). Also, RGS5 ribozyme
      enhanced angiotensin-stimulated inositol phosphate release. These results
      indicate the feasibility of using the ribozyme technology to determine the
      functional role of endogenous RGS proteins in signaling pathways and to define
      novel receptor-selective roles of endogenous RGS3 and RGS5 in modulating MAP
      kinase responses to either carbachol or angiotensin.

PMID- 12006603
TI  - Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin
      receptor.
AB  - The amyloid-beta (Abeta) peptide is neurotoxic and associated with the pathology
      of Alzheimer's disease (AD). We investigated the effect of Abeta peptides on
      insulin binding to the insulin receptor because it is known that (1) Abeta and
      insulin are both amyloidogenic peptides sharing a common sequence recognition
      motif, (2) Abeta and insulin are substrates for the same insulin degrading
      enzyme, and (3) impaired glucose metabolism is a characteristic event in the
      pathology of AD. We discovered that Abeta(1-40) and Abeta(1-42,) the main
      physiological forms, reduced insulin binding and receptor autophosphorylation.
      The reduction in binding was caused by a decrease in the affinity of insulin
      binding to the insulin receptor. This reduction was independent of the receptor
      concentration. The reverse, control peptide Abeta(40-1) did not reduce insulin
      binding or insulin receptor autophosphorylation. These results demonstrate that
      Abeta is a direct competitive inhibitor of insulin binding and action. We
      speculate that the increased levels of Abeta in Alzheimer's disease may be linked
      to the associated insulin resistance that has been observed previously in this
      disease.

PMID- 12006604
TI  - Lack of cocaine effect on dopamine clearance in the core and shell of the nucleus
      accumbens of dopamine transporter knock-out mice.
AB  - Cocaine produces its reinforcing effects primarily by inhibiting the dopamine
      transporter (DAT) at the level of presynaptic terminals and increasing
      extracellular levels of dopamine (DA). Surprisingly, in mice genetically lacking
      the DAT, cocaine was still able to elevate DA in the nucleus accumbens (NAc).
      This finding is critically important for explaining the persistence of cocaine
      reinforcement in DAT knock-out (DAT-KO) mice. However, the mechanism by which
      cocaine elevates DA is unclear. Here, we tested the recently proposed hypothesis
      that in the absence of the DAT, the norepinephrine transporter (NET) could
      provide an alternative uptake site for DA clearance. If true, cocaine could
      elevate DA levels through its inhibition of the NET. In vitro voltammetry, a
      technique well suited for evaluating the effects of drugs on DA uptake, was used
      in the present study. We report that both cocaine and desipramine, a potent NET
      inhibitor, failed to change DA clearance or evoked release in the NAc of mutant
      mice. Additionally, fluoxetine, a serotonin transporter (SERT) inhibitor, also
      had no effect on these parameters. These data rule out the involvement of
      accumbal NET or SERT in the cocaine-induced increase in extracellular DA in DAT
      KO mice. Moreover, the present findings suggest that in the DAT-KO mice, cocaine
      acts primarily outside the NAc to produce its effects.

PMID- 12006605
TI  - Receptors with different affinities mediate phasic and tonic GABA(A) conductances
      in hippocampal neurons.
AB  - A tonic inhibitory conductance mediated by GABA(A) receptors that supplements the
      phasic inhibition produced by IPSCs has been identified in the hippocampus and
      cerebellum. It is presently unknown whether tonic and phasic inhibitions are
      mediated by GABA(A) receptors with different subunit assemblies. Here we
      demonstrate that a low concentration (200 nm) of the highly specific competitive
      GABA(A) antagonist SR95531 (gabazine) reduces phasic inhibition in hippocampal
      granule cells by 71% but has no effect on tonic inhibition, whereas a high
      concentration (10 microm) of the antagonist blocked both conductances. These
      findings are consistent with tonic and phasic conductances being mediated by
      different GABA(A) receptor subtypes with different affinities for GABA.

PMID- 12006606
TI  - Failure of intravenous morphine to serve as an effective instrumental reinforcer
      in dopamine D2 receptor knock-out mice.
AB  - The rewarding effects of opiates are thought to be mediated through dopaminergic
      mechanisms in the ventral tegmental area, dopamine-independent mechanisms in the
      nucleus accumbens, or both. The purpose of the present study was to explore the
      contribution of dopamine to opiate-reinforced behavior using D2 receptor knock
      out mice. Wild-type, heterozygous, and D2 knock-out mice were first trained to
      lever press for water reinforcement and then implanted with intravenous
      catheters. The ability of intravenously delivered morphine to maintain lever
      pressing in these mice was studied under two schedules of reinforcement: a fixed
      ratio 4 (FR4) schedule (saline, 0.1, 0.3, or 1.0 mg/kg, per injection) and a
      progressive ratio (PR) schedule (1.0 mg/kg, per injection). In the wild-type and
      heterozygous mice, FR4 behavior maintained by morphine injections was
      significantly greater than behavior maintained by vehicle injections. Response
      rate was inversely related to injection dose and increased significantly in the
      wild-type and heterozygous mice when the animals were placed on the PR schedule.
      In contrast, the knock-out mice did not respond more for morphine than for saline
      and did not respond more when increased ratios were required by the PR schedule.
      Thus, morphine served as a positive reinforcer in the wild-type and heterozygous
      mice but failed to do so in the knock-out mice. Under this range of doses and
      response requirements, the rewarding effects of morphine appear to depend
      critically on an intact D2 receptor system.

PMID- 12006607
TI  - A system of blood analysis.

PMID- 12006608
TI  - Complexity in the secretory pathway: the assembly and secretion of apolipoprotein
      B-containing lipoproteins.

PMID- 12006609
TI  - How long does it take to train a scientist? By Caveman.

PMID- 12006610
TI  - Asymmetric cell division: microtubule dynamics and spindle asymmetry.
AB  - Asymmetric cell division can produce daughter cells with different developmental
      fates and is often accompanied by a difference in cell size. A number of recent
      genetic and in vivo imaging studies in Drosophila and Caenorhabditis elegans have
      begun to elucidate the mechanisms underlying the rearrangements of the
      cytoskeleton that result in eccentrically positioned cleavage planes. As a
      result, we are starting to gain an insight into the complex nature of the signals
      controlling cytoskeletal dynamics in the dividing cell. In this commentary we
      discuss recent findings on how the mitotic spindle is positioned and on cleavage
      site induction and place them in the context of cell size asymmetry in different
      model organisms.

PMID- 12006611
TI  - Emerging concepts of nucleolar assembly.
AB  - The nucleolus is a large nuclear domain and the site of ribosome biogenesis. It
      is also at the parting of the ways of several cellular processes, including cell
      cycle progression, gene silencing, and ribonucleoprotein complex formation.
      Consequently, a functional nucleolus is crucial for cell survival. Recent
      investigations of nucleolar assembly during the cell cycle and during
      embryogenesis have provided an integrated view of the dynamics of this process.
      Moreover, they have generated new ideas about cell cycle control of nucleolar
      assembly, the dynamics of the delivery of the RNA processing machinery, the
      formation of prenucleolar bodies, the role of precursor ribosomal RNAs in
      stabilizing the nucleolar machinery and the fact that nucleolar assembly is
      completed by cooperative interactions between chromosome territories. This has
      opened a new area of research into the dynamics of nuclear organization and the
      integration of nuclear functions.

PMID- 12006612
TI  - Rho-binding kinase (LET-502) and myosin phosphatase (MEL-11) regulate cytokinesis
      in the early Caenorhabditis elegans embryo.
AB  - Rho-binding kinase and myosin phosphatase regulate the contraction of actomyosin
      filaments in non-muscle and smooth muscle cells. Previously, we described the
      role of C. elegans genes encoding Rho-binding kinase (let-502) and myosin
      phosphatase targeting subunit (mel-11) in epidermal cell-shape changes that drive
      morphogenesis and in spermathecal contraction. Here we analyze their roles in a
      third contractile event, cytokinesis within early embryos. We demonstrate that
      these genes function together to regulate the rate of cleavage furrow
      contraction, with Rho-binding kinase/LET-502 mediating contraction, whereas
      myosin phosphatase/MEL-11 acts as a brake to contraction: early embryonic
      cleavage often fails or is slowed when let-502 is mutated, whereas mel-11
      mutations result in ectopic furrowing and faster furrow ingression. These
      phenotypes correspond to changes in the levels of phosphorylated regulatory non
      muscle myosin light chain (rMLC). The gene products of let-502 and mel-11
      colocalize at cleavage furrows, and their mutations alleviate one another's
      defects. rMLC is phosphorylated in let-502; mel-11 double mutants, indicating
      that a kinase is able to phosphorylate rMLC in the absence of both LET-502 and
      MEL-11. Genetic and molecular epistasis experiments place LET-502 and MEL-11 in a
      cytokinetic pathway. LET-502 and MEL-11 regulate the activity of non-muscle
      myosin after actin, non-muscle myosin heavy chain/NMY-2, regulatory non-muscle
      myosin light chain/MLC-4 and early formin/CYK-1 have formed a contractile ring.
      Proteins including Rho GTPase activating protein/CYK-4 and late CYK-1, which are
      required for late stages of cytokinesis, function downstream of LET-502 and MEL
      11.

PMID- 12006613
TI  - Tensile stress stimulates microtubule outgrowth in living cells.
AB  - Cell motility is driven by the sum of asymmetric traction forces exerted on the
      substrate through adhesion foci that interface with the actin cytoskeleton.
      Establishment of this asymmetry involves microtubules, which exert a
      destabilising effect on adhesion foci via targeting events. Here, we demonstrate
      the existence of a mechano-sensing mechanism that signals microtubule
      polymerisation and guidance of the microtubules towards adhesion sites under
      increased stress. Stress was applied either by manipulating the body of cells
      moving on glass with a microneedle or by stretching a flexible substrate that
      cells were migrating on. We propose a model for this mechano-sensing phenomenon
      whereby microtubule polymerisation is stimulated and guided through the
      interaction of a microtubule tip complex with actin filaments under tension.

PMID- 12006614
TI  - A ubiquitin C-terminal hydrolase is required to maintain osmotic balance and
      execute actin-dependent processes in the early C. elegans embryo.
AB  - In the early Caenorhabditis elegans embryo, establishment of cell polarity and
      cytokinesis are both dependent upon reorganization of the actin cytoskeleton.
      Mutations in the cyk-3 gene cause maternal effect embryonic lethality. Embryos
      produced by homozygous cyk-3 mutant animals become multinucleate. We have further
      analyzed the cyk-3 mutant phenotype and have found that cyk-3 mutant embryos fail
      to properly polarize the actin cytoskeleton and fail to segregate germline
      determinants. In addition, they fail to assemble an intact cleavage furrow.
      However, we have found that cyk-3 mutant embryos are intrinsically defective in
      osmotic regulation and that the cytokinesis defects can be partially rescued by
      providing osmotic support. The cyk-3 gene has been identified and found to encode
      a ubiquitin C-terminal hydrolase that is active against model substrates. These
      data indicate that the deubiquitination of certain substrates by CYK-3 is crucial
      for cellular osmoregulation. Defects in osmoregulation appear to indirectly
      affect actin-dependent processes.

PMID- 12006615
TI  - Biogenesis of Leishmania-harbouring parasitophorous vacuoles following
      phagocytosis of the metacyclic promastigote or amastigote stages of the
      parasites.
AB  - Protozoan parasites Leishmania alternate between a flagellated promastigote form
      and an amastigote form. In their mammalian hosts, Leishmania survive and multiply
      in macrophages. Both forms can be internalized by these host cells at different
      stages of the infectious process and eventually establish themselves within
      parasitophorous vacuoles exhibiting phagolysosomal properties. To determine
      whether the biogenesis of these organelles differs according to the parasitic
      stage used to initiate infection, we compared their formation kinetics after
      phagocytosis of either metacyclic promastigotes or amastigotes of L. amazonensis
      or of L. major by mouse bone-marrow-derived macrophages pre-exposed or not to IFN
      gamma. After 10 minutes of contact, an accumulation of F-actin was observed
      around the promastigotes and amatigotes undergoing phagocytosis or those that had
      already been internalized. This accumulation was transient and rapidly
      disappeared at later times. At 30 minutes, most of the promastigotes were located
      in long, narrow organelles that were exactly the same shape as the parasites. The
      latter were elongated with their cell bodies near to the macrophage nucleus and
      their flagella towards the periphery. This suggests that promastigote
      phagocytosis mainly occurs in a polarized manner, with the cell body entering the
      macrophages first. Most, if not all, of the phagocytosed promastigotes were
      located in organelles that rapidly acquired phagolysosomal properties. At 30
      minutes, lamp-1, macrosialin, cathepsins B and D were detected in 70-98% of these
      compartments and about 70% of them were surrounded by rab7p. These late
      endosome/lysosome 'markers' were recruited through fusion with late endocytic
      compartments. Indeed, when late endosomes/lysosomes were loaded with fluorescein
      dextran, 81-98% of the promastigote-harbouring compartments contained the
      endocytic tracer 30 minutes after infection. Electron microscopy of infected
      macrophages previously loaded with peroxidase confirmed that the phagosomes
      rapidly fused with late endocytic compartments. When the amastigote stage of L.
      amazonensis was used to initiate infection, the kinetics of acquisition of the
      different late endosome/lysosome 'markers' by the phagosomes were similar to
      those measured after infection with metacyclics. However, more rab7p(+)
      phagosomes were observed at early time points (e.g. 90% were rab7p(+) at 30
      minutes). The early endosome 'markers', EEA1 and the transferrin receptor, were
      hardly detected in parasite-containing compartments regardless of the parasitic
      stage used to infect macrophages and the time after infection. In conclusion,
      both metacyclic- and amastigote-containing phagosomes fuse with late
      endosomes/lysosomes within 30 minutes. However, with L. amazonensis, the time
      required for the formation of the huge parasitophorous vacuoles, which are
      characteristic of this species, was much shorter after infection with amastigotes
      than after infection with metacyclic promastigotes. This indicates that the
      initial fusions with late endosomes/lysosomes are followed by a stage-specific
      sequence of events.

PMID- 12006616
TI  - CENP-C binds the alpha-satellite DNA in vivo at specific centromere domains.
AB  - CENP-C is a fundamental component of the centromere, highly conserved among
      species and necessary for the proper assembly of the kinetochore structure and
      for the metaphase-anaphase transition. Although CENP-C can bind DNA in vitro, the
      identification of the DNA sequences associated with it in vivo and the
      significance of such an interaction have been, until now, elusive. To address
      this problem we took advantage of a chromatin-immunoprecipitation procedure and
      applied this technique to human HeLa cells. Through this approach we could
      establish that: (1) CENP-C binds the alpha-satellite DNA selectively; (2) the
      CENP-C region between amino acids 410 and 537, previously supposed to contain a
      DNA-binding domain, is indeed required to perform such a function in vivo; and
      (3) the profile of the alpha-satellite DNA associated with CENP-C is essentially
      identical to that recognized by CENP-B. However, further biochemical and
      ultrastructural characterization of CENP-B/DNA and CENP-C/DNA complexes, relative
      to their DNA components and specific spatial distribution in interphase nuclei,
      surprisingly reveals that CENP-C and CENP-B associate with the same types of
      alpha-satellite arrays but in distinct non-overlapping centromere domains. Our
      results, besides extending previous observations on the role of CENP-C in the
      formation of active centromeres, show, for the first time, that CENP-C can
      associate with the centromeric DNA sequences in vivo and, together with CENP-B,
      defines a highly structured organization of the alpha-satellite DNA within the
      human centromere.

PMID- 12006617
TI  - Distinct effects of thrombopoietin depending on a threshold level of activated
      Mpl in BaF-3 cells.
AB  - Thrombopoietin (TPO) plays a critical role in megakaryopoiesis through binding to
      its receptor Mpl. This involves activation of various intracellular signaling
      pathways, including phosphoinositide 3-kinase (PI3K) and the mitogen-activated
      protein kinase (MAPK) pathways. Their precise role in TPO-mediated proliferation,
      survival and differentiation is not fully understood. In the present study, we
      show that TPO induces different biological responses in Mpl-transduced BaF-3
      cells, depending on the cell surface density of Mpl and the resulting activation
      level of signaling pathways. TPO mediates cell proliferation in cells expressing
      high levels of Mpl but only mediates survival without proliferation in cells
      expressing low levels of the receptor. By using the kinase inhibitors PD98059 and
      LY294002, we further showed that the activation level of the PI3K and MAPK p42/44
      pathways is a determining factor for the proliferative effect. In cells
      expressing low levels of Mpl, the survival effect was strongly dependent on the
      activation level of the PI3K/AKT, but not the MAPK p42/44 pathway. Moreover, this
      effect was correlated with the phosphorylation level of BAD but not with the
      expression level of Bcl-X(L). However, PI3K pathway inhibition did not increase
      apoptosis when BaF-3 cells proliferated in response to TPO, indicating a
      compensating mechanism from other Mpl signaling pathways in this case.

PMID- 12006618
TI  - Osmoregulation in Paramecium: in situ ion gradients permit water to cascade
      through the cytosol to the contractile vacuole.
AB  - In vivo K(+), Na(+), Ca(2+) and Cl(-) activities in the cytosol and the
      contractile vacuole fluid of Paramecium multimicronucleatum were determined in
      cells adapted to a number of external osmolarities and ionic conditions by using
      ion-selective microelectrodes. It was found that: (1) under standardized saline
      conditions K(+) and Cl(-) were the major osmolytes in both the cytosol and the
      contractile vacuole fluid; and (2) the osmolarity of the contractile vacuole
      fluid, determined from K(+) and Cl(-) activities only, was always more than 1.5
      times higher than that of the cytosol. These findings indicate that excess
      cytosolic water crosses the contractile vacuole complex membrane osmotically.
      Substitution of choline or Ca(2+) for K(+) in the external solution or the
      external application of furosemide caused concomitant decreases in the cytosolic
      K(+) and Cl(-) activities that were accompanied by a decrease in the water
      segregation activity of the contractile vacuole complex. This implies that the
      cytosolic K(+) and Cl(-) are actively coimported across the plasma membrane.
      Thus, the osmotic gradients across both the plasma membrane and the membrane of
      the contractile vacuole complex ensure a controlled cascade of water flow through
      the cell that can provide for osmoregulation as well as the possible extrusion of
      metabolic waste by the contractile vacuole complex.

PMID- 12006619
TI  - Human melanocortin 1 receptor variants, receptor function and melanocyte response
      to UV radiation.
AB  - Cutaneous pigmentation is determined by the amounts of eumelanin and pheomelanin
      synthesized by epidermal melanocytes and is known to protect against sun-induced
      DNA damage. The synthesis of eumelanin is stimulated by the binding of alpha
      melanotropin (alpha-melanocyte-stimulating hormone) to the functional
      melanocortin 1 receptor (MC1R) expressed on melanocytes. The human MC1R gene is
      highly polymorphic and certain allelic variants of the gene are associated with
      red hair phenotype, melanoma and non-melanoma skin cancer. The importance of the
      MC1R gene in determining skin cancer risk led us to examine the impact of
      specific polymorphisms in this gene on the responses of human melanocytes to
      alpha-melanotropin and UV radiation. We compared the ability of human melanocyte
      cultures, each derived from a single donor, to respond to alpha-melanotropin with
      dose-dependent stimulation of cAMP formation, tyrosinase activity and
      proliferation. In each of those cultures the MC1R gene was sequenced, and the
      eumelanin and pheomelanin contents were determined. Human melanocytes homozygous
      for Arg160Trp, heterozygous for Arg160Trp and Asp294His, or for Arg151Cys and
      Asp294His substitutions, but not melanocytes homozygous for Val92Met
      substitution, in the MC1R demonstrated a significantly reduced response to alpha
      melanotropin. Additionally, melanocytes with a non-functional MC1R demonstrated a
      pronounced increase in their sensitivity to the cytotoxic effect of UV radiation
      compared with melanocytes expressing functional MC1R. We conclude that loss-of
      function mutations in the MC1R gene sensitize human melanocytes to the DNA
      damaging effects of UV radiation, which may increase skin cancer risk.

PMID- 12006620
TI  - Trimeric assembly of the C-terminal region of thrombospondin-1 or thrombospondin
      2 is necessary for cell spreading and fascin spike organisation.
AB  - Thrombospondin-1 (TSP-1) and the highly related protein thrombospondin-2 (TSP-2)
      are trimeric extracellular molecules that have complex roles in wound healing,
      angiogenesis and matrix organisation. At the cellular level, TSP-1 supports cell
      adhesion and migration by the organisation of fascin spike cytoskeletal
      structures. To define the molecular requirements for assembly of fascin spikes by
      thrombospondins, we developed a panel of recombinant protein units of TSP-1 and
      TSP-2; these were designed according to the domain boundaries and included
      matched monomeric and trimeric units. These proteins were tested for their
      effects on cell attachment and fascin spike organisation using C2C12 skeletal
      myoblasts and vascular smooth muscle cells. In monomeric units, cell attachment
      activity was localised to the type 1 repeats or type 3 repeats/C-terminal
      globule, and both regions need to be present in the same molecule for maximal
      activity. On a molar basis, cell-attachment activities with monomeric units were
      low compared with intact TSP-1, and no monomeric unit induced cell spreading.
      Trimeric versions of the type 1 repeats were more adhesive but did not induce
      cell spreading. Strikingly, trimers that contained the type 3 repeats/C-terminal
      globule of either TSP-1 or TSP-2 supported cell spreading and fascin spike
      organisation, producing a similar activity to intact TSP-1. We conclude that
      trimeric assembly of the highly conserved TSP C-terminal region is necessary for
      organisation of the fascin-based cytoskeletal structures that are needed for
      thrombospondin-induced cell motility.

PMID- 12006621
TI  - Calmodulin-containing substructures of the centrosomal matrix released by
      microtubule perturbation.
AB  - Calmodulin redistribution in MDCK and HeLa cells subjected to microtubule
      perturbations by antimitotic drugs was followed using a calmodulin-EGFP fusion
      protein that preserves the Ca(2+) affinity, target binding and activation
      properties of native calmodulin. CaM-EGFP targeting to spindle structures in
      normal cell division and upon spindle microtubule disruption allows evaluation of
      the dynamic redistribution of calmodulin in cell division. Under progressive
      treatment of stably transfected mammalian cells with nocodazole or vinblastine,
      the centrosomal matrix at the mitotic poles subdivides into numerous small 'star
      like' structures, with the calmodulin concentrated centrally, and partially
      distinct from the reduced microtubule mass to which kinetochores and chromosomes
      are attached. Prolonged vinblastine treatment causes the release of localised
      calmodulin into a uniform cytoplasmic distribution, and tubulin paracrystal
      formation. By contrast, paclitaxel treatment of metaphase cells apparently causes
      limited disassembly of the pericentriolar material into a number of multipolar
      'ring-like' structures containing calmodulin, each one having multiple attached
      microtubules terminating in the partially disordered kinetochore/chromosome
      complex. Thus drugs with opposite effects in either destabilising or stabilising
      mitotic microtubules cause subdivision of the centrosomal matrix into two
      distinctive calmodulin-containing structures, namely small punctate 'stars' or
      larger polar 'rings' respectively. The 'star-like' structures may represent an
      integral subcomponent for the attachment of kinetochore microtubules to the
      metaphase centrosome complex. The results imply that microtubules have a role in
      stabilising the structure of the pericentriolar matrix, involving interaction,
      either direct or indirect, with one or more proteins that are targets for binding
      of calmodulin. Possible candidates include the pericentriolar matrix-associated
      coiled-coil proteins containing calmodulin-binding motifs, such as myosin V,
      kendrin (PCNT2) and AKAP450.

PMID- 12006622
TI  - Intestinal stem cells protect their genome by selective segregation of template
      DNA strands.
AB  - The stem cells in the crypts of the small intestinal mucosa divide about a
      thousand times during the lifespan of a laboratory mouse, and yet they show
      little evidence of any decline in proliferative potential and rarely develop
      carcinogenic mutations, suggesting that their genome is extremely well protected.
      Protection against DNA-replication-induced errors can be achieved by the
      selective sorting of old (template) and new DNA strands with all template strands
      retained in the stem cell line. The template strands in the stem cells can be
      labelled during development or during tissue regeneration using tritiated
      thymidine ((3)HTdR). Labelling newly synthesised strands with a different marker
      (bromodeoxyuridine, BrdUrd) allows segregation of the two markers to be studied.
      Template strand label is retained ((3)HTdR), whereas label in the newly
      synthesised strands (BrdUrd) is lost following the second division of the stem
      cell. Random errors may occur in the template strands owing to environmental
      elements. These are protected against by the altruistic cell suicide (apoptosis)
      of the cells incurring such errors. A final level of protection for the tissue
      compensates for excessive deletion of stem cells via the apoptosis pathway. This
      is achieved by a hierarchical age structure in the stem cell compartment, with
      some cells being able to efficiently repair DNA damage and hence being more
      radioresistant. The presence of these protective mechanisms ensures that the
      small intestine rarely develops cancer and that stem cells can sustain the
      extensive cell proliferation needed during life.

PMID- 12006623
TI  - beta(2)-Microglobulin is important for cell surface expression and pH-dependent
      IgG binding of human FcRn.
AB  - FcRn is a heterodimer of an alpha-chain and beta(2)-microglobulin (beta(2)m) and
      differs from other IgG Fc receptors in that it is structurally related to MHC
      class I molecules. Several functions attributed to FcRn are affected in beta(2)
      microglobulin (beta(2)m)-deficient mice, suggesting that the alpha-chain needs to
      assemble with beta(2)m to form a functional receptor. However, the precise role
      of beta(2)m in FcRn function is not known. Here we expressed the human FcRn alpha
      chain alone or in combination with beta(2)m in human melanoma FO-1 cells. We show
      that beta(2)m is important for cell surface expression of FcRn and that, in the
      absence of beta(2)m, the receptor is retained in the endoplasmic reticulum.
      Furthermore, in the absence of beta(2)m, IgG binding is decreased compared with
      that of native FcRn. Thus, assembly of the FcRn alpha-chain with beta(2)m is
      important for both transport of FcRn from the ER to the cell surface and
      efficient pH-dependent IgG binding.

PMID- 12006624
TI  - Neuronal calcium sensor-1 binds to regulated secretory organelles and functions
      in basal and stimulated exocytosis in PC12 cells.
AB  - Neuronal calcium sensor-1 (NCS-1) and its non-mammalian homologue, frequenin,
      have been implicated in a spectrum of cellular processes, including regulation of
      stimulated exocytosis of synaptic vesicles and secretory granules (SGs) in
      neurons and neuroendocrine cells and regulation of phosphatidylinositol 4-kinase
      beta activity in yeast. However, apart from these intriguing putative functions,
      NCS-1 and frequenin are relatively poorly understood. Here, the distribution,
      dynamics and function of NCS-1 were studied using PC12 cells that stably express
      NCS-1-EYFP (NCS-1 fused to enhanced yellow fluorescent protein) or that stably
      overexpress NCS-1. Fluorescence and electron microscopies show that NCS-1-EYFP is
      absent from SGs but is present on small clear organelles, some of which are just
      below the plasma membrane. Total internal reflection fluorescence microscopy
      shows that NCS-1-EYFP is associated with synaptic-like microvesicles (SLMVs) in
      growth cones. Overexpression studies show that NCS-1 enhances exocytosis of
      synaptotagmin-labeled regulated secretory organelles (RSOs) under basal
      conditions and during stimulation by UTP. Significantly, these studies implicate
      NCS-1 in the enhancement of both basal and stimulated phosphoinositide-dependent
      exocytosis of RSOs in PC12 cells, and they show that NCS-1 is distributed
      strategically to interact with putative targets on the plasma membrane and on
      SLMVs. These studies also reveal that SLMVs undergo both fast directed motion and
      highly hindered diffusive motion in growth cones, suggesting that cytoskeletal
      constituents can both facilitate and hinder SLMV motion. These results also
      reveal interesting similarities and differences between transport organelles in
      differentiated neuroendocrine cells and neurons.

PMID- 12006625
TI  - Ectopic expression of Drosophila ELAV and human HuD in Drosophila wing disc cells
      reveals functional distinctions and similarities.
AB  - Drosophila ELAV and human HuD are two neuronal RNA binding proteins that show
      remarkable sequence homology, yet differ in their respective documented roles in
      post-transcriptional regulation. ELAV regulates neural-specific alternative
      splicing of specific transcripts, and HuD stabilizes specific mRNAs that are
      otherwise unstable due to AU-rich elements (AREs) in their 3' untranslated region
      (UTR). AREs are major determinants of transcript stability in mammalian cells.
      The role of each of these proteins was investigated and compared, by ectopically
      expressing them in Drosophila imaginal wing disc cells, which lack endogenous
      expression of either protein. The effect of the ectopic expression of ELAV and
      HuD was assessed on two sets of green fluorescent protein reporter transgenes,
      which were all driven with a broadly expressing promoter. Each set consisted of
      three reporter transgenes: (1) with an uninterrupted open reading frame (ORF);
      (2) with a constitutively spliced intron inserted into the ORF; and (3) with the
      intron nASI whose splicing is regulated in neurons by ELAV, inserted into the
      ORF. The two sets differed from each other only in their 3'UTR: Heat-shock
      protein-70Ab (Hsp70Ab) trailer with ARE-like characteristics or Actin 5C (Act5C)
      trailer. Our results show that: (1) both ectopically expressed ELAV and HuD can
      enhance expression of transgenes with the Hsp70Ab 3'UTR, but not of transgenes
      with Act5C 3'UTR; (2) this enhancement is accompanied by an increase in mRNA
      level; (3) only ELAV can induce neural-specific splicing of nASI; and (4)
      although HuD is localized primarily to the cytoplasm, ELAV is localized to both
      the cytoplasm and the nucleus.

PMID- 12006626
TI  - The plant Spc98p homologue colocalizes with gamma-tubulin at microtubule
      nucleation sites and is required for microtubule nucleation.
AB  - The molecular basis of microtubule nucleation is still not known in higher plant
      cells. This process is better understood in yeast and animals cells. In the yeast
      spindle pole body and the centrosome in animal cells, gamma-tubulin small
      complexes and gamma-tubulin ring complexes, respectively, nucleate all
      microtubules. In addition to gamma-tubulin, Spc98p or its homologues plays an
      essential role. We report here the characterization of rice and Arabidopsis
      homologues of SPC98. Spc98p colocalizes with gamma-tubulin at the nuclear surface
      where microtubules are nucleated on isolated tobacco nuclei and in living cells.
      AtSpc98p-GFP also localizes at the cell cortex. Spc98p is not associated with
      gamma-tubulin along microtubules. These data suggest that multiple microtubule
      nucleating sites are active in plant cells. Microtubule nucleation involving
      Spc98p-containing gamma-tubulin complexes could then be conserved among all
      eukaryotes, despite differences in structure and spatial distribution of
      microtubule organizing centers.

PMID- 12006627
TI  - Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP
      activated protein kinase (AMPK).
AB  - In the rat liver epithelial cell line Clone 9, the V(max) for glucose uptake is
      acutely increased by inhibition of oxidative phosphorylation and by osmotic
      stress. By using a membrane-impermeant photoaffinity labelling reagent together
      with an isoform-specific antibody, we have, for the first time, provided direct
      evidence for the involvement of the GLUT1 glucose transporter isoform in this
      response. Transport stimulation was found to be associated with enhanced
      accessibility of GLUT1 to its substrate and with photolabelling of formerly
      'cryptic' exofacial substrate binding sites in GLUT1 molecules. The total amount
      of cell surface GLUT1 remained constant. The precise mechanism for this binding
      site 'unmasking' is unclear but appears to involve AMP-activated protein kinase:
      in the current study, osmotic and metabolic stresses were found to result in
      activation of the alpha 1 isoform of AMP-activated protein kinase, and transport
      stimulation could be mimicked both by 5-aminoimidazole-4-carboxamide
      ribonucleoside and by infection of cells with a recombinant adenovirus encoding
      constitutively active AMP-activated protein kinase. The effect of 5
      aminoimidazole-4-carboxamide ribonucleoside, as for metabolic stress, was on the
      V(max) rather than on the K(m) for transport and did not affect the cell-surface
      concentration of GLUT1. The relevant downstream target(s) of AMP-activated
      protein kinase have not yet been identified, but stimulation of transport by
      inhibition of oxidative phosphorylation or by 5-aminoimidazole-4-carboxamide
      ribonucleoside was not prevented by either inhibitors of conventional and novel
      protein kinase C isoforms or inhibitors of nitric oxide synthase. These enzymes,
      which have been implicated in stress-regulated pathways in other cell types, are
      therefore unlikely to play a role in transport regulation by stress in Clone 9
      cells.

PMID- 12006628
TI  - BiP is feed-back regulated by control of protein translation efficiency.
AB  - The lumenal endoplasmic reticulum (ER) protein BiP, among its other functions, is
      believed to serve as an ER stress sensor, triggering the so-called 'unfolded
      protein response' or UPR. For this role, BiP levels are critical. Indeed, here we
      show that BiP expression is tightly controlled at a post-transcriptional level.
      Thus, an artificial increase in cellular BiP mRNA does not lead to increased
      synthesis of BiP in unstressed cells, and, consequently, protein levels remain
      constant. Under ER stress conditions, however, this homeostatic restriction is
      alleviated, and independent of transcript levels, the translation efficiency of
      BiP transcripts is enhanced, allowing the cells to produce more protein. We
      additionally show that this regulation is independent of elements in the 5' and
      3' UTR of BiP mRNA, which rather points to a novel type of translational feedback
      control. BiP is the first example of a lumenal protein whose expression is
      controlled at a translational level. The implications of these findings with
      respect to cellular stress are discussed.

PMID- 12006629
TI  - Weight loss expectations in patients with binge-eating disorder.
AB  - OBJECTIVE: To study weight loss expectations in patients with binge-eating
      disorder and to examine whether expectations differed by sex and motivation for
      treatment. RESEARCH METHODS AND PROCEDURES: One hundred and thirty patients (104
      women and 26 men), aged 23 to 61 (mean age, 43.0 years), with BED completed a
      measure of desired weights that included their dream weight, happy weight,
      acceptable weight, and disappointed weight. In a structured interview,
      participants were asked their primary motivation for seeking treatment
      (appearance or health) and their lowest adult weight (LAW). RESULTS: The BED
      participants reported weight loss expectations that far exceeded expert and
      governmental guidelines. In this sample, desired dream body mass index (BMI),
      happy BMI, and acceptable BMI averaged reductions in current weight of 36%, 29%,
      and 23%, respectively. Even the "disappointed" BMI was an average 14% reduction
      in current weight, and was 1.5 to 3 times greater than the expert recommendation
      (5% to 10%). Comparisons of desired weights were significantly different for
      women and men, whereas percent reductions from current weight were not. Although
      weight goal expectations were significantly lower for those motivated by
      appearance, compared with those motivated by health, percent reductions for
      current weight were not. Desired dream weight correlated with reported LAW, and
      the mean difference between these weights was not significant. DISCUSSION: These
      findings suggest that patients with BED have weight loss expectations that far
      exceed expert and governmental guidelines and that these expectations do not
      differ by sex or motivation for seeking treatment. One possible explanation for
      these unrealistic desired weights may be the patients' recollections of their
      LAWs.

PMID- 12006630
TI  - Body-image perceptions among urban Native American youth.
AB  - OBJECTIVE: This study investigated body-image perceptions among Native American
      youth. RESEARCH METHODS AND PROCEDURES: A modified and validated body-image
      measure for use with Native American youth was utilized in a cross-sectional
      assessment of 155 urban Native American youth attending an after-school program
      in Minneapolis, Minnesota. The youth (ages 5 to 18 years) expressed their
      perceptions of current and ideal body image, which allowed assessment of
      satisfaction or dissatisfaction. Body sizes perceived as healthy or most likely
      to develop diabetes were also communicated. Heights and weights were measured,
      and body mass index was calculated. RESULTS: When asked to identify their ideal
      body figure, younger children selected thinner figures than adolescents, and
      overweight youth chose ideal figures similar to those of normal-weight youth. The
      mean body dissatisfaction of the youth was +/-0.99 and +/-1.49 body figures for
      boys and girls, respectively. Examination of the direction of body
      dissatisfaction revealed that 41% of the boys and 61% of the girls expressed a
      desire to be thinner. Those expressing the greatest dissatisfaction were
      overweight girls (>95th percentile). On a scale from one to eight, the median of
      the body image viewed as the healthiest was 4.0, whereas that most likely to
      develop diabetes was 8.0. DISCUSSION: These results suggest that urban Native
      American youth are dissatisfied with their body size and that most acknowledge
      the diabetes risk associated with overweight, which implies that they may be
      receptive to obesity prevention measures.

PMID- 12006631
TI  - Body weight modulates cholesterol metabolism in non-insulin dependent type 2
      diabetics.
AB  - OBJECTIVE: Cholesterol metabolism was studied in 64 subjects with type 2 diabetes
      who had body weight ranging from normal to obese, to find out whether weight
      interferes with cholesterol metabolism in diabetes. RESEARCH METHODS AND
      PROCEDURES: Cholesterol absorption was measured with peroral isotopes and by
      assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol
      synthesis with sterol balance, and measuring serum cholesterol precursor ratios.
      RESULTS: The study population was divided into normal-weight (body mass index,
      24.1 +/- 0.4 kg/m2; mean +/- SEM; n = 20) and obese (31.0 +/- 0.5 kg/m2; n = 44)
      groups. Despite similar serum cholesterol and blood glucose values, fecal neutral
      sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649
      +/- 78 vs. 1077 +/- 52 mg/d; p < 0.001), and serum cholesterol precursors were
      higher, and cholesterol absorption % (32 +/- 1 vs. 40 +/- 2%; p < 0.05), serum
      cholestanol, and plant sterols were lower in the obese vs. the non-obese groups.
      Serum sex hormone-binding globulin was positively associated with variables of
      cholesterol absorption, whereas blood glucose, serum insulin, and body mass index
      were associated with variables of cholesterol synthesis. In multiple stepwise
      regression analysis, cholesterol absorption percentage (R2 = 24%) and body mass
      index (R2 = 15%) were the only variables explaining the variability of
      cholesterol synthesis. DISCUSSION: Body weight, through its entire range,
      regulates cholesterol metabolism in type 2 diabetes such that with increasing
      insulin resistance, cholesterol absorption is lowered and cholesterol synthesis
      increased.

PMID- 12006632
TI  - Racial differences in insulin resistance and mid-thigh fat deposition in
      postmenopausal women.
AB  - OBJECTIVE: To determine whether racial differences in insulin resistance between
      African American (AA) and white women exist in postmenopausal women and whether
      they are related to physical fitness and/or obesity. RESEARCH METHODS AND
      PROCEDURES: We studied 35 obese AA (n = 9) and white (n = 26) women of comparable
      maximal oxygen consumption, obesity, and age. Total body fat was measured by DXA.
      Abdominal and mid-thigh low-density lean tissue (a marker of intramuscular fat)
      were determined with computed tomography. Glucose utilization (M) was measured
      during the last 30 minutes of a 3-hour hyperinsulinemic-euglycemic clamp. Insulin
      sensitivity was estimated from the relationship of M to the concentration of
      insulin during the last 30 minutes of the clamp. RESULTS: The percentage of fat
      and total body fat mass were similar between AA and white women, whereas fat-free
      mass was higher in African American women. Visceral adipose tissue was not
      different between groups, but subcutaneous abdominal fat was 17% higher in the AA
      than in the white women. AA women had an 18% greater mid-thigh muscle area (p <
      0.01) and a 34% greater mid-thigh low-density lean tissue area than the white
      women. Fasting glucose concentrations were not different, but fasting insulin
      concentrations were 29% higher in AA women. Glucose utilization was 60% lower in
      the AA women because of a lower non-oxidative glucose disposal. Insulin
      sensitivity was 46% lower in the AA women. DISCUSSION: AA postmenopausal women
      have more mid-thigh intramuscular fat, lower glucose utilization, and are less
      insulin sensitive than white women despite comparable fitness and relative body
      fat levels.

PMID- 12006633
TI  - Sex, race/ethnicity, socioeconomic status, and BMI in relation to self-perception
      of overweight.
AB  - OBJECTIVE: To compare the self-perception of overweight in the study population
      according to sex, race/ethnicity, and socioeconomic status and to compare the
      self-perception of overweight among individuals classified as normal weight,
      overweight, and obese. RESEARCH METHODS AND PROCEDURES: Data from 5440 adults who
      participated in the 1994 to 1996 Continuing Survey of Food Intakes by Individuals
      and the Diet and Health Knowledge Survey conducted by the U.S. Department of
      Agriculture were analyzed. Data for analysis included self-perceived weight
      status, self-reported weight and height, and demographic and socioeconomic data.
      Underweight individuals, defined as those with a body mass index <18.5 kg/m2,
      were excluded from the analysis. RESULTS: Self-perception of overweight was more
      common in women compared with men and in whites compared with blacks or
      Hispanics. Both the correct and incorrect perception of overweight was more
      common in normal weight and overweight white women compared with black women.
      More overweight and obese white men correctly perceived their overweight status
      compared with black men. Multiple logistic regression showed that the odds ratio
      of perceived overweight was significantly higher in women, whites, and
      individuals with higher body mass index, higher income, and higher education.
      DISCUSSION: Self-perceived overweight varied by sex, race/ethnicity, and
      socioeconomic status. Erroneous perception of body weight may have important
      health and behavioral implications. In particular, a considerable proportion of
      overweight men may be at risk of obesity if they continue to perceive themselves
      as having normal weight.

PMID- 12006634
TI  - Familial resemblance for plasma leptin: sample homogeneity across adiposity and
      ethnic groups.
AB  - OBJECTIVE: Previous studies show a wide range in the percentage of variance in
      leptin levels attributable to genetic factors. These studies differ markedly with
      respect to ethnicity, study design, and statistical methodology. Therefore, the
      purpose of this study was to investigate heterogeneity hypotheses across ethnic
      groups and by adiposity level, using the same statistical methods. RESEARCH
      METHODS AND PROCEDURES: Samples included black vs. white (HERITAGE Family Study)
      and random vs. obese (Quebec Family Study) individuals from 432 families (1432
      individuals). Heritability for leptin, alternatively adjusted for age and sex and
      then for age, sex, and adiposity was estimated with the use of familial
      correlations. Heterogeneity in the magnitude of the familial resemblance between
      samples and the effect of adjusting for adiposity was explored. RESULTS:
      Heritability did not vary across samples stratified by adiposity level or ethnic
      group or across adjustment schemes. Maximal heritability, the percentage of
      additive phenotypic variability due to all familial sources, was 32%. DISCUSSION:
      Whereas leptin and adiposity were highly correlated within individuals, removing
      the effects of adiposity did not significantly alter the magnitude of the
      familial component for leptin. Moreover, this effect did not vary as a function
      of ethnicity (black vs. white) or adiposity level. Thus, no evidence for
      heterogeneity was detected. However, a comparison among previous studies raises
      questions concerning possible genetic heterogeneity in other ethnic groups in
      which complex interactions among leptin, adiposity, and diabetes status may be
      important.

PMID- 12006635
TI  - A prospective study of adiposity and all-cause mortality: the Malmo Diet and
      Cancer Study.
AB  - OBJECTIVE: This study aims to examine the association between various measures of
      adiposity and all-cause mortality in Swedish middle-aged and older men and women
      and, additionally, to describe the influences of age and sex on these
      associations. RESEARCH METHODS AND PROCEDURES: A prospective analysis was
      performed in a cohort of 10,902 men and 16,814 women ages 45 to 73 years who
      participated in the Malmo Diet and Cancer Study in Sweden. Baseline examinations
      took place between 1991 and 1996, and 982 deaths were documented during an
      average follow-up of 5.7 years. All-cause mortality was related to the following
      variables measured at baseline: body mass index (BMI), percentage of body fat,
      lean body mass (LBM), and waist-to-hip ratio (WHR), with adjustment for age and
      selected covariates. Body composition data were derived from bioelectrical
      impedance analysis. RESULTS: The association between percentage of body fat and
      mortality was modified by age, particularly in women. For instance, fatness was
      associated with excess mortality in the younger women but with reduced mortality
      in the older women. Weaker associations were seen for BMI than for percentage of
      body fat in both sexes. Placement in the top quintiles of waist-to-hip ratio,
      independent of overall body fat, was a stronger predictor of mortality in women
      than in men. The observed associations could not be explained by bias from early
      death or antecedent disease. DISCUSSION: The findings reveal sex and age
      differences for the effects of adiposity and WHR on mortality and indicate the
      importance of considering direct measures of adiposity, as opposed to BMI, when
      describing obesity-related mortality risks.

PMID- 12006636
TI  - Trends in energy intake in U.S. between 1977 and 1996: similar shifts seen across
      age groups.
AB  - OBJECTIVE: To determine the trends in locations and food sources of Americans
      stratified by age group for both total energy and the meal and snack
      subcomponents. RESEARCH METHODS AND PROCEDURES: Nationally representative data
      was taken from the 1977 to 1978 Nationwide Food Consumption Survey and the 1989
      to 1991 and 1994 to 1996 (and 1998 for children age 2 through 9) Continuing
      Surveys of Food Intake by Individuals. The sample consisted of 63,380
      individuals, age 2 and up. For each survey year, the percentage of total energy
      intake from meals and snacks was calculated separately for 2- to 18-year-olds, 19
      to 39-year-olds, 40- to 59-year-olds, and those 60 years and older. The
      percentage of energy intake by location (at-home consumption or preparation,
      vending, store eaten out, restaurant/fast-food, and school) and by specific food
      group was computed for all age groups separately. RESULTS: The trends in location
      and food sources were almost identical for all age groups. Key dietary behavior
      shifts included greater away-from-home consumption; large increases in total
      energy from salty snacks, soft drinks, and pizza; and large decreases in energy
      from low- and medium-fat milk and medium- and high-fat beef and pork. DISCUSSION:
      Total energy intake has increased over the past 20 years, with shifts away from
      meals to snacks and from at-home to away-from-home consumption. The similarity of
      changes across all age groups furthers the assertion that broad-based
      environmental changes are needed to improve the diets of Americans.

PMID- 12006637
TI  - Physical activity, TV viewing, and weight in U.S. youth: 1999 Youth Risk Behavior
      Survey.
AB  - OBJECTIVE: To examine the relationship between physical activity, TV watching,
      and weight in U.S. youth ages 14 to 18 years. RESEARCH METHODS AND PROCEDURES:
      Data from a nationally representative sample of 15,143 U.S. high-school students
      participating in the 1999 Centers for Disease Control and Prevention (CDC) Youth
      Risk Behavior Survey were examined. Prevalence rates of participation in moderate
      physical activity (MPA), vigorous physical activity (VPA), and television
      watching (TV) were determined. The association between MPA, VPA, TV and the body
      mass index (BMI) and overweight status (BMI > or =85th percentile of age- and sex
      specific CDC/National Center for Health Statistics reference values) were
      examined by analysis of covariance and logistic regression. RESULTS: Overall, 45%
      reported participating in MPA > or =3 d/wk, 65% reported participating in VPA >
      or =3 d/wk, and 25% reported watching TV > or =4 h/school day. Boys reporting six
      to seven bouts of MPA had a significantly lower BMI compared with boys reporting
      three to five or less than two. The mean BMI differed significantly between the
      lowest and highest levels of MPA groups in girls. The mean BMI was significantly
      lower in the highest VPA group compared with the other two groups in both sexes.
      There was a significant graded response for BMI across all levels of TV.
      Decreased levels of MPA and 3 to 4 days of VPA were significantly associated with
      an increased risk of overweight in boys when compared with those engaging in 6 to
      7 d/wk (odds ratio = 1.26 to 1.37). A graded response existed between TV and
      overweight in both sexes. Boys and girls were approximately 20% to 25% less
      likely to be classified as overweight if they reported 2 to 3 hours of TV per day
      and approximately 40% less likely to be classified as overweight if they reported
      < or =1 hour of TV per day compared with those who watched > or =4 hours of TV.
      In general, youth who engaged in less physical activity watched more TV per week.
      DISCUSSION: Increased levels of physical activity are associated with a lower BMI
      and less TV watching. However, the relationship between TV watching and weight
      status is more pronounced.

PMID- 12006638
TI  - Adolescent obesity, overt and relational peer victimization, and romantic
      relationships.
AB  - OBJECTIVE: To examine associations between obesity and peer relations in
      adolescents, specifically testing the hypotheses that obese adolescents are more
      frequent victims of peer aggression and are less likely to develop romantic
      relationships. RESEARCH METHODS AND PROCEDURES: Measures of overt and relational
      victimization, as well as dating status and satisfaction, were collected for a
      group of 416 ninth- through twelfth-grade students (51.7% girls). Body mass index
      was computed for each teen based on self-reported height and weight data.
      RESULTS: Results revealed that obese boys reported more overt victimization and
      obese girls reported more relational victimization compared with their average
      weight peers. Obese girls were also less likely to date than their peers.
      However, both obese boys and girls reported being more dissatisfied with their
      dating status compared with average-weight peers. DISCUSSION: The results suggest
      that obese adolescents are at greater risk for mistreatment by peers and may have
      fewer opportunities to develop intimate romantic relationships; this may
      contribute to the psychological and health difficulties frequently associated
      with obesity.

PMID- 12006639
TI  - Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in
      women.
AB  - OBJECTIVE: Resting metabolic rate (RMR) is mainly determined by fat-free mass and
      additionally by age, sex, hormones, and possibly genetic differences. We
      evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR)
      gene were associated with energy expenditure phenotypes. METHODS: RMR, body
      composition, and leptin levels were measured in 125 overweight and obese women.
      Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on
      genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein,
      and carbohydrate oxidation were calculated for 103 of these subjects. In 38
      subjects, glucose-induced thermogenesis was measured over 3 hours. RESULTS: In
      the first study group, a negative correlation between RMR and leptin levels was
      found after controlling for fat and fat-free mass. In multiple regression
      analysis, leptin contributed significantly to RMR, independent of body
      composition. In the second study group, RMR was not associated with LEPR
      polymorphisms. Differences in substrate oxidation rates were found among
      genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend
      to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which
      became significant after the glucose load when carbohydrate oxidation rate in
      Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation
      rate was 44% lower (p = 0.02). DISCUSSION: These results suggest that DNA
      sequence variations in the LEPR gene could affect substrate oxidation. We
      hypothesize that this might be caused by differences in glucose levels, leading
      to differences in glucose oxidation rates.

PMID- 12006640
TI  - Association of the TNF-alpha -308 G/A promoter polymorphism with insulin
      resistance in obesity.
AB  - OBJECTIVE: Obesity is a major risk factor for the development of type 2 diabetes.
      Tumor necrosis factor (TNF)-alpha is a candidate gene for the development of both
      obesity and insulin resistance. We investigated whether a common polymorphism in
      the promoter region (-308 G/A) of the TNF-alpha gene was associated with
      increased risk for the development of insulin resistance and cardiovascular
      disease in an obese Australian population. RESEARCH METHODS AND PROCEDURES:
      Obese, non-diabetic subjects (146 women and 34 men) were genotyped with
      polymerase chain reaction-restriction fragment length polymorphism techniques,
      and anthropometric and biochemical measurements were analyzed. A homeostasis
      model assessment (HOMA) score was used to gauge the level of insulin resistance.
      RESULTS: The frequencies of the G allele and the A allele were 0.759 and 0.241,
      respectively. Subjects homozygous for the A allele had higher fasting insulin
      levels (226 vs. 131 pM; p < 0.001), higher HOMA scores (10.2 vs. 5.3; p < 0.001),
      higher systolic blood pressure (143 vs. 129 mm Hg; p = 0.02), and lower high
      density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p = 0.04) than did
      subjects homozygous for the G allele. Whereas an association between insulin
      resistance and body mass index or waist circumference was seen in all subjects, a
      highly significant negative correlation of HDL cholesterol to HOMA scores (r = 
      0.710; p < 0.001) occurred in subjects with the A allele only. DISCUSSION: The 
      308 G/A TNF-alpha gene variant conveys an increased risk for the development of
      insulin resistance in obese subjects. The presence of low HDL cholesterol levels
      further increases the risks associated with insulin resistance in carriers of the
      A allele.

PMID- 12006641
TI  - Liver volume and visceral obesity in women with hepatic steatosis undergoing
      gastric banding.
AB  - OBJECTIVE: To investigate the relationships between visceral obesity and hepatic
      steatosis in obese patients undergoing adjustable silicone gastric banding with
      the LAP-BAND. RESEARCH METHODS AND PROCEDURES: Six premenopausal, morbidly obese
      women with an ultrasonographic diagnosis of liver steatosis were evaluated before
      surgery and 8 and 24 weeks after surgery. Liver volume and body fat distribution
      were simultaneously analyzed by total-body multislices magnetic resonance
      imaging. RESULTS: Before surgery, the only variable found to be correlated with
      liver volume was visceral adipose tissue volume (r = 0.91; p < 0.01). Weight loss
      was 9.9 +/- 3.8 kg in the period from 0 to 8 weeks (p < 0.01) and 7.1 +/- 4.9 kg
      in the the period from 8 to 24 weeks (p < 0.05). Total fat showed a statistically
      significant reduction of 6.2 +/- 4.0 liters in the 0- to 8-week period and a
      further significant reduction of 7.7 +/- 3.9 liters in the 8- to 24-week period.
      Visceral adipose tissue showed a statistically significant reduction of 1.0 +/-
      0.9 liters in the 0- to 8-week period (p < 0.05) but only a further, not
      significant reduction of 0.6 +/- 0.7 liters in the 8- to 24-week period. The
      relative reduction of visceral fat in the 0-to 8-week period was higher than the
      relative reduction of total fat. Liver volume also showed a statistically
      significant reduction of 0.24 +/- 0.26 liters in the first phase of weight loss
      (p < 0.05), corresponding to a relative reduction of 12.3 +/- 10.6%. During the 8
      to 24-week period, liver volume was substantially stable. DISCUSSION:
      Hepatomegaly was associated with visceral obesity in morbidly obese women with
      liver steatosis. In the phase of rapid weight loss after gastric surgery, a
      preferential mobilization of visceral fat, compared with total adipose tissue,
      occurred. This preferential visceral fat loss was associated with a significant
      reduction in liver volume.

PMID- 12006642
TI  - Effect of group vs. single housing on phenotypic variance in C57BL/6J mice.
AB  - OBJECTIVE: To determine if group housing affects the variance of body composition
      parameters in a highly inbred mouse strain. RESEARCH METHODS AND PROCEDURES:
      Thirty 3-week-old male C57BL/6J mice were obtained from the Jackson Laboratory.
      Fifteen mice were housed individually, and 15 mice were housed in groups of
      5/cage. Animals were fed ad libitum and maintained in the same room under a 12:12
      hour light/dark photoperiod at 22 degrees C for 9 weeks. Animals were killed, and
      fat mass, soft-lean tissue mass, bone mineral density (BMD), and bone mineral
      content (BMC) were determined by DXA. At necropsy, weights of the paired
      epididymal fat pads, paired retroperitoneal fat pads, right inguinal fat pad,
      liver, kidneys, paired testes, and seminal vesicles were obtained. RESULTS:
      Relative to mice housed singly, group-housed mice showed significantly greater
      variance in percentage of body fat, testes weight, and BMC. Group-housed mice
      tended to show greater variance in liver weights and BMD. Mice housed singly were
      smaller, had less soft-lean tissue mass and BMC, and lower BMD when compared with
      group-housed mice. DISCUSSION: These results suggest that with respect to body
      composition parameters, mice housed singly are more similar to one another than
      are group-housed mice, most likely because of a reduction in environmental
      (predominately behavioral/social) effects. Thus, mice housed singly may be more
      representative of genotypic effects on body composition than group-housed mice.
      Whether other inbred strains of mice show similar responses to housing condition
      is unknown.

PMID- 12006643
TI  - Competition of spontaneous protein folding and mitochondrial import causes dual
      subcellular location of major adenylate kinase.
AB  - Sorting of cytoplasmically synthesized proteins to their target compartments
      usually is highly efficient so that cytoplasmic precursor pools are negligible
      and a particular gene product occurs at one subcellular location only. Yeast
      major adenylate kinase (Adk1p/Aky2p) is one prominent exception to this rule. In
      contrast to most mitochondrial proteins, only a minor fraction (6-8%) is taken up
      into the mitochondrial intermembrane space, whereas the bulk of the protein
      remains in the cytosol in sequence-identical form. We demonstrate that
      Adk1p/Aky2p uses a novel mechanism for subcellular partitioning between cytoplasm
      and mitochondria, which is based on competition between spontaneous protein
      folding and mitochondrial targeting and import. Folding is spontaneous and rapid
      and can dispense with molecular chaperons. After denaturation, enzymatic activity
      of Adk1p/Aky2p returns within a few minutes and, once folded, the protein is
      thermally and proteolytically very stable. In an uncoupled cell-free organellar
      import system, uptake of Adk1p/Aky2p is negligible, but can be improved by
      previous chaotropic denaturation. Import ensues independently of Hsp70 or
      membrane potential. Thus, nascent Adk1p/Aky2p has two options: either it is
      synthesized to completion and folds into an enzymatically active import
      incompetent conformation that remains in the cytosol; or, during synthesis and
      before commencement of significant tertiary structure formation, it reaches a
      mitochondrial surface receptor and is internalized.

PMID- 12006644
TI  - Crk adapter proteins promote an epithelial-mesenchymal-like transition and are
      required for HGF-mediated cell spreading and breakdown of epithelial adherens
      junctions.
AB  - Activation of the Met receptor tyrosine kinase through its ligand, hepatocyte
      growth factor (HGF), promotes an epithelial-mesenchymal transition and cell
      dispersal. However, little is known about the HGF-dependent signals that regulate
      these events. HGF stimulation of epithelial cell colonies leads to the enhanced
      recruitment of the CrkII and CrkL adapter proteins to Met-dependent signaling
      complexes. We provide evidence that signals involving CrkII and CrkL are required
      for the breakdown of adherens junctions, the spreading of epithelial colonies,
      and the formation of lamellipodia in response to HGF. The overexpression of a
      CrkI SH3 domain mutant blocks these HGF-dependent events. In addition, the
      overexpression of CrkII or CrkL promotes lamellipodia formation, loss of adherens
      junctions, cell spreading, and dispersal of colonies of breast cancer epithelial
      cells in the absence of HGF. Stable lines of epithelial cells overexpressing
      CrkII show enhanced activation of Rac1 and Rap1. The Crk-dependent breakdown of
      adherens junctions and cell spreading is inhibited by the expression of a
      dominant negative mutant of Rac1 but not Rap1. These findings provide evidence
      that Crk adapter proteins play a critical role in the breakdown of adherens
      junctions and the spreading of sheets of epithelial cells.

PMID- 12006645
TI  - SpSld3 is required for loading and maintenance of SpCdc45 on chromatin in DNA
      replication in fission yeast.
AB  - Initiation of DNA replication in eukaryotic cells is regulated through the
      ordered assembly of replication complexes at origins of replication. Association
      of Cdc45 with the origins is a crucial step in assembly of the replication
      machinery, hence can be considered a target for the regulation of origin
      activation. To examine the process required for SpCdc45 loading, we isolated
      fission yeast SpSld3, a counterpart of budding yeast Sld3 that interacts with
      Cdc45. SpSld3 associates with the replication origin during G1-S phases and this
      association depends on Dbf4-dependent (DDK) kinase activity. In the corresponding
      period, SpSld3 interacts with minichromosome maintenance (MCM) proteins and then
      with SpCdc45. A temperature-sensitive sld3-10 mutation suppressed by the
      multicopy of the sna41+ encoding SpCdc45 impairs loading of SpCdc45 onto
      chromatin. In addition, this mutation leads to dissociation of preloaded Cdc45
      from chromatin in the hydroxyurea-arrested S phase, and DNA replication upon
      removal of hydroxyurea is retarded. Thus, we conclude that SpSld3 is required for
      stable association of Cdc45 with chromatin both in initiation and elongation of
      DNA replication. The DDK-dependent origin association suggests that SpSld3 is
      involved in temporal regulation of origin firing.

PMID- 12006646
TI  - Dephosphorylation of cell cycle-regulated proteins correlates with anoxia-induced
      suspended animation in Caenorhabditis elegans.
AB  - Some metazoans have evolved the capacity to survive severe oxygen deprivation.
      The nematode, Caenorhabditis elegans, exposed to anoxia (0 kPa, 0% O(2)) enters
      into a recoverable state of suspended animation during all stages of the life
      cycle. That is, all microscopically observable movement ceases including cell
      division, developmental progression, feeding, and motility. To understand
      suspended animation, we compared oxygen-deprived embryos to nontreated embryos in
      both wild-type and hif-1 mutants. We found that hif-1 mutants survive anoxia,
      suggesting that the mechanisms for anoxia survival are different from those
      required for hypoxia. Examination of wild-type embryos exposed to anoxia show
      that blastomeres arrest in interphase, prophase, metaphase, and telophase but not
      anaphase. Analysis of the energetic state of anoxic embryos indicated a
      reversible depression in the ATP to ADP ratio. Given that a decrease in ATP
      concentrations likely affects a variety of cellular processes, including signal
      transduction, we compared the phosphorylation state of several proteins in anoxic
      embryos and normoxic embryos. We found that the phosphorylation state of histone
      H3 and cell cycle-regulated proteins recognized by the MPM-2 antibody were not
      detectable in anoxic embryos. Thus, dephosphorylation of specific proteins
      correlate with the establishment and/or maintenance of a state of anoxia-induced
      suspended animation.

PMID- 12006647
TI  - Identification of Sec36p, Sec37p, and Sec38p: components of yeast complex that
      contains Sec34p and Sec35p.
AB  - The Saccharomyces cerevisiae proteins Sec34p and Sec35p are components of a large
      cytosolic complex involved in protein transport through the secretory pathway.
      Characterization of a new secretion mutant led us to identify SEC36, which
      encodes a new component of this complex. Sec36p binds to Sec34p and Sec35p, and
      mutation of SEC36 disrupts the complex, as determined by gel filtration. Missense
      mutations of SEC36 are lethal with mutations in COPI subunits, indicating a
      functional connection between the Sec34p/sec35p complex and the COPI vesicle
      coat. Affinity purification of proteins that bind to Sec35p-myc allowed
      identification of two additional proteins in the complex. We call these two
      conserved proteins Sec37p and Sec38p. Disruption of either SEC37 or SEC38 affects
      the size of the complex that contains Sec34p and Sec35p. We also examined COD4,
      COD5, and DOR1, three genes recently reported to encode proteins that bind to
      Sec35p. Each of the eight genes that encode components of the Sec34p/sec35p
      complex was tested for its contribution to cell growth, protein transport, and
      the integrity of the complex. These tests indicate two general types of subunits:
      Sec34p, Sec35p, Sec36p, and Sec38p seem to form the essential core of a complex
      to which Sec37p, Cod4p, Cod5p, and Dor1p seem to be peripherally attached.

PMID- 12006648
TI  - Spindle checkpoint requires Mad1-bound and Mad1-free Mad2.
AB  - The spindle checkpoint prevents anaphase from occurring until all chromosomes
      have attached properly to the mitotic spindle. The checkpoint components Mad1 and
      Mad2 associate with unattached kinetochores and are probably involved in
      triggering the checkpoint. We now demonstrate that in Xenopus egg extracts Mad1
      and Mad2 form a stable complex, whereas a fraction of Mad2 molecules is not bound
      to Mad1. The checkpoint establishment and maintenance are lost upon titrating out
      free Mad2 with an excess of Mad1 or a truncated Mad1 (amino acids 326-718, Mad1C)
      that contains the Mad2-binding region. Mad1N (amino acids 1-445) that binds
      kinetochores, but not Mad2, reduces Mad1 and Mad2 at kinetochores and abolishes
      checkpoint maintenance. Furthermore, the association between Mad2 and Cdc20, the
      activator for the anaphase-promoting complex, is enhanced under checkpoint-active
      condition compared with that at metaphase. Immunodepletion analysis shows that
      the Mad1-free Mad2 protein is unable to bind Cdc20, consistent with the model
      that kinetochore localization of Mad2 facilitates the formation of Mad2-Cdc20
      complex. This study demonstrates that the ratio between Mad1 and Mad2 is critical
      for maintaining a pool of Mad1-free Mad2 that is necessary for the spindle
      checkpoint. We propose that Mad2 may become activated and dissociated from Mad1
      at kinetochores and is replenished by the pool of Mad1-free Mad2.

PMID- 12006649
TI  - Utrophin binds laterally along actin filaments and can couple costameric actin
      with sarcolemma when overexpressed in dystrophin-deficient muscle.
AB  - Dystrophin is widely thought to mechanically link the cortical cytoskeleton with
      the muscle sarcolemma. Although the dystrophin homolog utrophin can functionally
      compensate for dystrophin in mice, recent studies question whether utrophin can
      bind laterally along actin filaments and anchor filaments to the sarcolemma.
      Herein, we have expressed full-length recombinant utrophin and show that the
      purified protein is fully soluble with a native molecular weight and molecular
      dimensions indicative of monomers. We demonstrate that like dystrophin, utrophin
      can form an extensive lateral association with actin filaments and protect actin
      filaments from depolymerization in vitro. However, utrophin binds laterally along
      actin filaments through contribution of acidic spectrin-like repeats rather than
      the cluster of basic repeats used by dystrophin. We also show that the defective
      linkage between costameric actin filaments and the sarcolemma in dystrophin
      deficient mdx muscle is rescued by overexpression of utrophin. Our results
      demonstrate that utrophin and dystrophin are functionally interchangeable actin
      binding proteins, but that the molecular epitopes important for filament binding
      differ between the two proteins. More generally, our results raise the
      possibility that spectrin-like repeats may enable some members of the plakin
      family of cytolinkers to laterally bind and stabilize actin filaments.

PMID- 12006650
TI  - Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor
      endocytosis visualized in living cells.
AB  - Activation of the epidermal growth factor receptor (EGFR) triggers multiple
      signaling pathways and rapid endocytosis of the epidermal growth factor (EGF)
      receptor complexes. To directly visualize the compartmentalization of molecules
      involved in the major signaling cascade, activation of Ras GTPase, we constructed
      fusions of Grb2, Shc, H-Ras, and K-Ras with enhanced cyan fluorescent protein
      (CFP) or yellow fluorescent protein (YFP), and used live-cell fluorescence
      imaging microscopy combined with the fluorescence resonance energy transfer
      (FRET) technique. Stimulation of cells by EGF resulted in the accumulation of
      large pools of Grb2-CFP and YFP-Shc in endosomes, where these two adaptor
      proteins formed a complex with EGFR. H-Ras and K-Ras fusion proteins were found
      at the plasma membrane, particularly in ruffles and lamellipodia, and also in
      endosomes independently of GTP/GDP loading and EGF stimulation. The relative
      amount of endosomal H-Ras was higher than that of K-Ras, whereas K-Ras
      predominated at the plasma membrane. On application of EGF, Grb2, and Ras
      converge in the same endosomes through the fusion of endosomes containing either
      Grb2 or Ras or through the joint internalization of two proteins from the plasma
      membrane. To examine the localization of the GTP-bound form of Ras, we used a
      FRET assay that exploits the specific interaction of GTP-bound CFP-Ras with the
      YFP-fused Ras binding domain of c-Raf. FRET microscopy revealed that GTP-bound
      Ras is located at the plasma membrane, mainly in ruffles and at the cell edges,
      as well as in endosomes containing EGFR. These data point to the potential for
      endosomes to serve as sites of generation for persistent signaling through Ras.

PMID- 12006651
TI  - Targeted destruction of DNA replication protein Cdc6 by cell death pathways in
      mammals and yeast.
AB  - The highly conserved Cdc6 protein is required for initiation of eukaryotic DNA
      replication and, in yeast and Xenopus, for the coupling of DNA replication to
      mitosis. Herein, we show that human Cdc6 is rapidly destroyed by a p53
      independent, proteasome-, and ubiquitin-dependent pathway during early stages of
      programmed cell death induced by the DNA-damaging drug adozelesin, or by a
      separate caspase-dependent pathway in cells undergoing apoptosis through an
      extrinsic pathway induced by tumor necrosis factor-alpha and cycloheximide. The
      proteasome-dependent pathway induced by adozelesin is conserved in the budding
      yeast Saccharomyces cerevisiae. The destruction of Cdc6 may be a primordial
      programmed death response that uncouples DNA replication from the cell division
      cycle, which is reinforced in metazoans by the evolution of caspases and p53.

PMID- 12006652
TI  - Paxillin-dependent paxillin kinase linker and p21-activated kinase localization
      to focal adhesions involves a multistep activation pathway.
AB  - The precise temporal-spatial regulation of the p21-activated serine-threonine
      kinase PAK at the plasma membrane is required for proper cytoskeletal
      reorganization and cell motility. However, the mechanism by which PAK localizes
      to focal adhesions has not yet been elucidated. Indirect binding of PAK to the
      focal adhesion protein paxillin via the Arf-GAP protein paxillin kinase linker
      (PKL) and PIX/Cool suggested a mechanism. In this report, we demonstrate an
      essential role for a paxillin-PKL interaction in the recruitment of activated PAK
      to focal adhesions. Similar to PAK, expression of activated Cdc42 and Rac1, but
      not RhoA, stimulated the translocation of PKL from a generally diffuse
      localization to focal adhesions. Expression of the PAK regulatory domain (PAK1
      329) or the autoinhibitory domain (AID 83-149) induced PKL, PIX, and PAK
      localization to focal adhesions, indicating a role for PAK scaffold activation.
      We show PIX, but not NCK, binding to PAK is necessary for efficient focal
      adhesion localization of PAK and PKL, consistent with a PAK-PIX-PKL linkage.
      Although PAK activation is required, it is not sufficient for localization. The
      PKL amino terminus, containing the PIX-binding site, but lacking paxillin-binding
      subdomain 2 (PBS2), was unable to localize to focal adhesions and also abrogated
      PAK localization. An identical result was obtained after PKLDeltaPBS2 expression.
      Finally, neither PAK nor PKL was capable of localizing to focal adhesions in
      cells overexpressing paxillinDeltaLD4, confirming a requirement for this motif in
      recruitment of the PAK-PIX-PKL complex to focal adhesions. These results suggest
      a GTP-Cdc42/GTP-Rac triggered multistep activation cascade leading to the
      stimulation of the adaptor function of PAK, which through interaction with PIX
      provokes a functional PKL PBS2-paxillin LD4 association and consequent
      recruitment to focal adhesions. This mechanism is probably critical for the
      correct subcellular positioning of PAK, thereby influencing the ability of PAK to
      coordinate cytoskeletal reorganization associated with changes in cell shape and
      motility.

PMID- 12006653
TI  - Probing for membrane domains in the endoplasmic reticulum: retention and
      degradation of unassembled MHC class I molecules.
AB  - Quality control of protein biosynthesis requires ER-retention and ER-associated
      degradation (ERAD) of unassembled/misfolded molecules. Although some evidence
      exists for the organization of the ER into functionally distinct membrane
      domains, it is unknown if such domains are involved in the retention and ERAD of
      unassembled proteins. Here, it is shown that unassembled MHC class I molecules
      are retained in the ER without accumulating at ER-exit sites or in the ERGIC of
      beta2m-/- cells. Furthermore, these molecules did not cluster in the ER membrane
      and appeared to be highly mobile even when ERAD or their association with
      calnexin were inhibited. However, upon ATP depletion, they were reversibly
      segregated into an ER membrane domain, distinct from ER exit sites, which
      included calnexin and COPII, but not the ERGIC marker protein p58. This quality
      control domain was also observed upon prolonged inhibition of proteasomes.
      Microtubules were required for its appearance. Segregation of unfolded proteins,
      ER-resident chaperones, and COPII may be a temporal adaptation to cell stress.

PMID- 12006654
TI  - Selective and signal-dependent recruitment of membrane proteins to secretory
      granules formed by heterologously expressed von Willebrand factor.
AB  - von Willebrand factor (vWF) is a large, multimeric protein secreted by
      endothelial cells and involved in hemostasis. When expressed in AtT-20 cells, vWF
      leads to the de novo formation of cigar-shaped organelles similar in appearance
      to the Weibel-Palade bodies of endothelial cells in which vWF is normally stored
      before regulated secretion. The membranes of this vWF-induced organelle, termed
      the pseudogranule, are uncharacterized. We have examined the ability of these
      pseudogranules, which we show are secretagogue responsive, to recruit membrane
      proteins. Coexpression experiments show that the Weibel-Palade body proteins P
      selectin and CD63, as well as the secretory organelle membrane proteins vesicle
      associated membrane protein-2 and synaptotagmin I are diverted away from the
      endogenous adrenocorticotropic hormone-containing secretory granules to the vWF
      containing pseudogranules. However, transferrin receptor, lysosomal-associated
      membrane protein 1, and sialyl transferase are not recruited. The recruitment of
      P-selectin is dependent on a tyrosine-based motif within its cytoplasmic domain.
      Our data show that vWF pseudogranules specifically recruit a subset of membrane
      proteins, and that in a process explicitly driven by the pseudogranule content
      (i.e., vWF), the active recruitment of at least one component of the
      pseudogranule membrane (i.e., P-selectin) is dependent on residues of P-selectin
      that are cytosolic and therefore unable to directly interact with vWF.

PMID- 12006655
TI  - t-SNARE phosphorylation regulates endocytosis in yeast.
AB  - Earlier we demonstrated that activation of a ceramide-activated protein
      phosphatase (CAPP) conferred normal growth and secretion to yeast lacking their
      complement of exocytic v-SNAREs (Snc1,2) or bearing a temperature-sensitive
      mutation in an exocytic t-SNARE (Sso2). CAPP activation led to Sso
      dephosphorylation and enhanced the assembly of t-SNAREs into functional
      complexes. Thus, exocytosis in yeast is modulated by t-SNARE phosphorylation.
      Here, we show that endocytic defects in cells lacking the v- and t-SNAREs
      involved in endocytosis are also rescued by CAPP activation. Yeast lacking the
      Tlg1 or Tlg2 t-SNAREs, the Snc v-SNAREs, or both, undergo endocytosis after
      phosphatase activation. CAPP activation correlated with restored uptake of FM4-64
      to the vacuole, the uptake and degradation of the Ste2 receptor after mating
      factor treatment, and the dephosphorylation and assembly of Tlg1,2 into SNARE
      complexes. Activation of the phosphatase by treatment with C(2)-ceramide, VBM/ELO
      gene inactivation, or by the overexpression of SIT4 was sufficient to confer
      rescue. Finally, we found that mutation of single PKA sites in Tlg1 (Ser31 to
      Ala31) or Tlg2 (Ser90 to Ala90) was sufficient to restore endocytosis, but not
      exocytosis, to snc cells. These results suggest that endocytosis is also
      modulated by t-SNARE phosphorylation in vivo.

PMID- 12006656
TI  - Discrimination between paralogs using microarray analysis: application to the
      Yap1p and Yap2p transcriptional networks.
AB  - Ohno [Ohno, S. (1970) in Evolution by Gene Duplication, Springer, New York]
      proposed that gene duplication with subsequent divergence of paralogs could be a
      major force in the evolution of new gene functions. In practice the functional
      differences between closely related homologues produced by duplications can be
      subtle and difficult to separate experimentally. Here we show that DNA
      microarrays can distinguish the functions of two closely related homologues from
      the yeast Saccharomyces cerevisiae, Yap1p and Yap2p. Although Yap1p and Yap2p are
      both bZIP transcription factors involved in multiple stress responses and are 88%
      identical in their DNA binding domains, our work shows that these proteins
      activate nonoverlapping sets of genes. Yap1p controls a set of genes involved in
      detoxifying the effects of reactive oxygen species, whereas Yap2p controls a set
      of genes over represented for the function of stabilizing proteins. In addition
      we show that the binding sites in the promoters of the Yap1p-dependent genes
      differ from the sites in the promoters of Yap2p-dependent genes and we validate
      experimentally that these differences are important for regulation by Yap1p. We
      conclude that while Yap1p and Yap2p may have some overlapping functions they are
      clearly not redundant and, more generally, that DNA microarray analysis will be
      an important tool for distinguishing the functions of the large numbers of highly
      conserved genes found in all eukaryotic genomes.

PMID- 12006657
TI  - Characterization of signal that directs C-tail-anchored proteins to mammalian
      mitochondrial outer membrane.
AB  - We analyzed the signal that directs the outer membrane protein with the C
      terminal transmembrane segment (TMS) to mammalian mitochondria by using yeast
      Tom5 as a model and green fluorescent protein as a reporter. Deletions or
      mutations were systematically introduced into the TMS or the flanking regions and
      their intracellular localization in COS-7 cells was examined using confocal
      microscopy and cell fractionation. 1) Three basic amino acid residues within the
      C-terminal five-residue segment (C-segment) contained the information required
      for mitochondrial-targeting. Reduction of the net positive charge in this segment
      decreased mitochondrial specificity, and the mutants were distributed throughout
      the intracellular membranes. 2) Elongation of the TMS interfered with the
      function of the C-segment and the mutants were delivered to the intracellular
      membranes. 3) Separation of the TMS and C-segment by linker insertion severely
      impaired mitochondrial targeting function, leading to mislocalization to the
      cytoplasm. 4) Mutations or small deletions in the region of the TMS flanking the
      C-segment also impaired the mitochondrial targeting. Therefore, the moderate
      length of the TMS, the positive charges in the C-segment, and the distance
      between or context of the TMS and C-segment are critical for the targeting
      signal. The structural characteristics of the signal thus defined were also
      confirmed with mammalian C-tail-anchored protein OMP25.

PMID- 12006658
TI  - Sum1, a component of the fission yeast eIF3 translation initiation complex, is
      rapidly relocalized during environmental stress and interacts with components of
      the 26S proteasome.
AB  - Eukaryotic translation initiation factor 3 (eIF3) is a multisubunit complex that
      plays a central role in translation initiation. We show that fission yeast Sum1,
      which is structurally related to known eIF3 subunits in other species, is
      essential for translation initiation, whereas its overexpression results in
      reduced global translation. Sum1 is associated with the 40S ribosome and
      interacts stably with Int6, an eIF3 component, in vivo, suggesting that Sum1 is a
      component of the eIF3 complex. Sum1 is cytoplasmic under normal growth
      conditions. Surprisingly, Sum1 is rapidly relocalized to cytoplasmic foci after
      osmotic and thermal stress. Int6 and p116, another putative eIF3 subunit, behave
      similarly, suggesting that eIF3 is a dynamic complex. These cytoplasmic foci,
      which additionally comprise eIF4E and RNA components, may function as translation
      centers during environmental stress. After heat shock, Sum1 additionally
      colocalizes stably with the 26S proteasome at the nuclear periphery. The
      relationship between Sum1 and the 26S proteasome was further investigated, and we
      find cytoplasmic Sum1 localization to be dependent on the 26S proteasome.
      Furthermore, Sum1 interacts with the Mts2 and Mts4 components of the 26S
      proteasome. These data indicate a functional link between components of the
      structurally related eIF3 translation initiation and 26S proteasome complexes.

PMID- 12006659
TI  - Caenorhabditis elegans inositol 5-phosphatase homolog negatively regulates
      inositol 1,4,5-triphosphate signaling in ovulation.
AB  - Ovulation in Caenorhabditis elegans requires inositol 1,4,5-triphosphate (IP(3))
      signaling activated by the epidermal growth factor (EGF)-receptor homolog LET-23.
      We generated a deletion mutant of a type I 5-phosphatase, ipp-5, and found a
      novel ovulation phenotype whereby the spermatheca hyperextends to engulf two
      oocytes per ovulation cycle. The temporal and spatial expression of IPP-5 is
      consistent with its proposed inhibition of IP(3) signaling in the adult
      spermatheca. ipp-5 acts downstream of let-23, and interacts with let-23-mediated
      IP(3) signaling pathway genes. We infer that IPP-5 negatively regulates IP(3)
      signaling to ensure proper spermathecal contraction.

PMID- 12006660
TI  - Systematic structure-function analysis of the small GTPase Arf1 in yeast.
AB  - Members of the ADP-ribosylation factor (Arf) family of small GTPases are
      implicated in vesicle traffic in the secretory pathway, although their precise
      function remains unclear. We generated a series of 23 clustered charge-to-alanine
      mutations in the Arf1 protein of Saccharomyces cerevisiae to determine the
      portions of this protein important for its function in cells. These mutants
      display a number of phenotypes, including conditional lethality at high or low
      temperature, defects in glycosylation of invertase, dominant lethality, fluoride
      sensitivity, and synthetic lethality with the arf2 null mutation. All mutations
      were mapped onto the available crystal structures for Arf1p: Arf1p bound to GDP,
      to GTP, and complexed with the regulatory proteins ArfGEF and ArfGAP. From this
      systematic structure-function analysis we demonstrate that all essential
      mutations studied map to one hemisphere of the protein and provide strong
      evidence in support of the proposed ArfGEF contact site on Arf1p but minimal
      evidence in support of the proposed ArfGAP-binding site. In addition, we describe
      the isolation of a spatially distant intragenic suppressor of a dominant lethal
      mutation in the guanine nucleotide-binding region of Arf1p.

PMID- 12006661
TI  - Symplekin, a constitutive protein of karyo- and cytoplasmic particles involved in
      mRNA biogenesis in Xenopus laevis oocytes.
AB  - Symplekin is a dual location protein that has been localized to the cytoplasmic
      plaques of tight junctions but also occurs in the form of interchromatin
      particles in the karyoplasm. Here we report the identification of two novel and
      major symplekin-containing protein complexes in both the karyo- and the cytoplasm
      of Xenopus laevis oocytes. Buffer-extractable fractions from the karyoplasm of
      stage IV-VI oocytes contain an 11S particle, prepared by immunoselection and
      sucrose gradient centrifugation, in which symplekin is associated with the
      subunits of the cleavage and polyadenylation specificity factor (CPSF). Moreover,
      in immunofluorescence microscopy nuclear symplekin colocalizes with protein CPSF
      100 in the "Cajal bodies." However, symplekin is also found in cytoplasmic
      extracts of enucleated oocytes and egg extracts, where it occurs in 11S as well
      as in ca. 65S particles, again in association with CPSF-100. This suggests that,
      in X. laevis oocytes, symplekin is possibly involved in both processes, 3'-end
      processing of pre-mRNA in the nucleus and regulated polyadenylation in the
      cytoplasm. We discuss the possible occurrence of similar symplekin-containing
      particles involved in mRNA metabolism in the nucleus and cytoplasm of other kinds
      of cells, also in comparison with the nuclear forms of other dual location
      proteins in nuclei and cell junctions.

PMID- 12006662
TI  - Novel mechanism for regulation of epidermal growth factor receptor endocytosis
      revealed by protein kinase A inhibition.
AB  - Current models put forward that the epidermal growth factor receptor (EGFR) is
      efficiently internalized via clathrin-coated pits only in response to ligand
      induced activation of its intrinsic tyrosine kinase and is subsequently directed
      into a lysosomal-proteasomal degradation pathway by mechanisms that include
      receptor tyrosine phosphorylation and ubiquitylation. Herein, we report a novel
      mechanism of EGFR internalization that does not require ligand binding, receptor
      kinase activity, or ubiquitylation and does not direct the receptor into a
      degradative pathway. Inhibition of basal protein kinase A (PKA) activity by H89
      and the cell-permeable substrate peptide Myr-PKI induced internalization of 40
      60% unoccupied, inactive EGFR, and its accumulation into early endosomes without
      affecting endocytosis of transferrin and mu-opioid receptors. This effect was
      abrogated by interfering with clathrin function. Thus, the predominant
      distribution of inactive EGFR at the plasma membrane is not simply by default but
      involves a PKA-dependent restrictive condition resulting in receptor avoidance of
      endocytosis until it is stimulated by ligand. Furthermore, PKA inhibition may
      contribute to ligand-induced EGFR endocytosis because epidermal growth factor
      inhibited 26% of PKA basal activity. On the other hand, H89 did not alter ligand
      induced internalization of EGFR but doubled its half-time of down-regulation by
      retarding its segregation into degradative compartments, seemingly due to a delay
      in the receptor tyrosine phosphorylation and ubiquitylation. Our results reveal
      that PKA basal activity controls EGFR function at two levels: 1) residence time
      of inactive EGFR at the cell surface by a process of "endocytic evasion,"
      modulating the accessibility of receptors to stimuli; and 2) sorting events
      leading to the down-regulation pathway of ligand-activated EGFR, determining the
      length of its intracellular signaling. They add a new dimension to the fine
      tuning of EGFR function in response to cellular demands and cross talk with other
      signaling receptors.

PMID- 12006664
TI  - Repression and activation domains of RME1p structurally overlap, but differ in
      genetic requirements.
AB  - Rme1p, a repressor of meiosis in the yeast Saccharomyces cerevisiae, acts as both
      a transcriptional repressor and activator. Rme1p is a zinc-finger protein with no
      other homology to any protein of known function. The C-terminal DNA binding
      domain of Rme1p is essential for function. We find that mutations and progressive
      deletions in all three zinc fingers can be rescued by fusion of RME1 to the DNA
      binding domain of another protein. Thus, structural integrity of the zinc fingers
      is not required for the Rme1p-mediated effects on transcription. Using a series
      of mutant Rme1 proteins, we have characterized domains responsible for repression
      and activation. We find that the minimal transcriptional repression and
      activation domains completely overlap and lie in an 88-amino-acid N-terminal
      segment (aa 61-148). An additional transcriptional effector determinant lies in
      the first 31 amino acids of the protein. Notwithstanding the complete overlap
      between repression and activation domains of Rme1p, we demonstrated a functional
      difference between repression and activation: Rgr1p and Sin4p are absolutely
      required for repression but dispensable for activation.

PMID- 12006663
TI  - Yeast Vps55p, a functional homolog of human obesity receptor gene-related
      protein, is involved in late endosome to vacuole trafficking.
AB  - The Saccharomyces cerevisiae VPS55 (YJR044c) gene encodes a small protein of 140
      amino acids with four potential transmembrane domains. VPS55 belongs to a family
      of genes of unknown function, including the human gene encoding the obesity
      receptor gene-related protein (OB-RGRP). Yeast cells with a disrupted VPS55
      present normal vacuolar morphology, but exhibit an abnormal secretion of the
      Golgi form of the soluble vacuolar carboxypeptidase Y. However, trafficking of
      the membrane-bound vacuolar alkaline phosphatase remains normal. The endocytosis
      of uracil permease, used as an endocytic marker, is normal in vps55Delta cells,
      but its degradation is delayed and this marker transiently accumulates in late
      endosomal compartments. We also found that Vps55p is mainly localized in the late
      endosomes. Collectively, these results indicate that Vps55p is involved in late
      endosome to vacuole trafficking. Finally, we show that human OB-RGRP displays the
      same distribution as Vps55p and corrects the phenotypic defects of the vps55Delta
      strain. Therefore, the function of Vps55p has been conserved throughout
      evolution. This study highlights the importance of the multispanning Vps55p and
      OB-RGRP in membrane trafficking to the vacuole/lysosome of eukaryotic cells.

PMID- 12006665
TI  - PLAC-24 is a cytoplasmic dynein-binding protein that is recruited to sites of
      cell-cell contact.
AB  - We screened for polypeptides that interact specifically with dynein and
      identified a novel 24-kDa protein (PLAC-24) that binds directly to dynein
      intermediate chain (DIC). PLAC-24 is not a dynactin subunit, and the binding of
      PLAC-24 to the dynein intermediate chain is independent of the association
      between dynein and dynactin. Immunocytochemistry using PLAC-24-specific
      polyclonal antibodies revealed a punctate perinuclear distribution of the
      polypeptide in fibroblasts and isolated epithelial cells. However, as epithelial
      cells in culture make contact with adjacent cells, PLAC-24 is specifically
      recruited to the cortex at sites of contact, where the protein colocalizes with
      components of the adherens junction. Disruption of the cellular cytoskeleton with
      latrunculin or nocodazole indicates that the localization of PLAC-24 to the
      cortex is dependent on intact actin filaments but not on microtubules.
      Overexpression of beta-catenin also leads to a loss of PLAC-24 from sites of cell
      cell contact. On the basis of these data and the recent observation that
      cytoplasmic dynein is also localized to sites of cell-cell contact in epithelial
      cells, we propose that PLAC-24 is part of a multiprotein complex localized to
      sites of intercellular contact that may function to tether microtubule plus ends
      to the actin-rich cellular cortex.

PMID- 12006666
TI  - Rab27a is an essential component of melanosome receptor for myosin Va.
AB  - Melanocytes that lack the GTPase Rab27a (ashen) are disabled in myosin Va
      dependent melanosome capture because the association of the myosin with the
      melanosome surface depends on the presence of this resident melanosomal membrane
      protein. One interpretation of these observations is that Rab27a functions wholly
      or in part as the melanosome receptor for myosin Va (Myo5a). Herein, we show that
      the ability of the myosin Va tail domain to localize to the melanosome and
      generate a myosin Va null (dilute) phenotype in wild-type melanocytes is
      absolutely dependent on the presence of exon F, one of two alternatively spliced
      exons present in the tail of the melanocyte-spliced isoform of myosin Va but not
      the brain-spliced isoform. Exon D, the other melanocyte-specific tail exon, is
      not required. Similarly, the ability of full-length myosin Va to colocalize with
      melanosomes and to rescue their distribution in dilute melanocytes requires exon
      F but not exon D. These results predict that an interaction between myosin Va and
      Rab27a should be exon F dependent. Consistent with this, Rab27a present in
      detergent lysates of melanocytes binds to beads coated with purified, full-length
      melanocyte myosin Va and melanocyte myosin Va lacking exon D, but not to beads
      coated with melanocyte myosin Va lacking exon F or brain myosin Va. Moreover, the
      preparation of melanocyte lysates in the presence of GDP rather than guanosine-5'
      O-(3-thio)triphosphate reduces the amount of Rab27a bound to melanocyte myosin Va
      coated beads by approximately fourfold. Finally, pure Rab27a does not bind to
      myosin Va-coated beads, suggesting that these two proteins interact indirectly.
      Together, these results argue that Rab27a is an essential component of a protein
      complex that serves as the melanosome receptor for myosin Va, suggest that this
      complex contains at least one additional protein capable of bridging the indirect
      interaction between Rab27a and myosin Va, and imply that the recruitment of
      myosin Va to the melanosome surface in vivo should be regulated by factors
      controlling the nucleotide state of Rab27a.

PMID- 12006667
TI  - Inhibitors of COP-mediated transport and cholera toxin action inhibit simian
      virus 40 infection.
AB  - Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from
      surface caveolae to the endoplasmic reticulum in an apparently novel infectious
      entry pathway. We now show that the initial entry step is blocked by brefeldin A
      and by incubation at 20 degrees C. Subsequent to the entry step, the virus
      reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This
      intracellular trafficking pathway is also brefeldin A sensitive. Infection is
      strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1
      (Arf1) and Sar1 mutants and by microinjection of antibodies to betaCOP. In
      addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N
      benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera
      toxin action. Our results identify novel inhibitors of SV40 infection and show
      that SV40 requires COPI- and COPII-dependent transport steps for successful
      infection.

PMID- 12006668
TI  - Evidence for a posttranscriptional role of a TFIIICalpha-like protein in
      Chironomus tentans.
AB  - We have cloned and sequenced a cDNA that encodes for a nuclear protein of 238 kDa
      in the dipteran Chironomus tentans. This protein, that we call p2D10, is
      structurally similar to the alpha subunit of the general transcription factor
      TFIIIC. Using immunoelectron microscopy we have shown that a fraction of p2D10 is
      located at sites of transcription, which is consistent with a possible role of
      this protein in transcription initiation. We have also found that a large
      fraction of p2D10 is located in the nucleoplasm and in the nuclear pore
      complexes. Using gel filtration chromatography and coimmunoprecipitation methods,
      we have identified and characterized two p2D10-containing complexes that differ
      in molecular mass and composition. The heavy p2D10-containing complex contains at
      least one other component of the TFIIIC complex, TFIIIC-epsilon. Based on its
      molecular mass and composition, the heavy p2D10-containing complex may be the Pol
      III holoenzyme. The light p2D10-containing complex contains RNA together with at
      least two proteins that are thought to be involved in mRNA trafficking, RAE1 and
      hrp65. The observations reported here suggest that this new TFIIIC-alpha-like
      protein is involved in posttranscriptional steps of premRNA metabolism in
      Chironomus tentans.

PMID- 12006669
TI  - Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in
      invertebrate neurons.
AB  - The endoplasmic reticulum (ER) is divided into rough and smooth domains (RER and
      SER). The two domains share most proteins, but RER is enriched in some membrane
      proteins by an unknown mechanism. We studied RER protein targeting by expressing
      fluorescent protein fusions to ER membrane proteins in Caenorhabditis elegans. In
      several cell types RER and general ER proteins colocalized, but in neurons RER
      proteins were concentrated in the cell body, whereas general ER proteins were
      also found in neurites. Surprisingly RER membrane proteins diffused rapidly
      within the cell body, indicating they are not localized by immobilization.
      Ribosomes were also concentrated in the cell body, suggesting they may be in part
      responsible for targeting RER membrane proteins.

PMID- 12006671
TI  - Calcium, contractions, and tropomyosin Focus on "divergent abnormal muscle
      relaxation by hypertrophic cardiomyopathy and nemaline myopathy mutant
      tropomyosins".

PMID- 12006670
TI  - Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site
      that allows efficient translation during normoxia and hypoxia.
AB  - HIF-1alpha is the regulated subunit of the HIF-1 transcription factor, which
      induces transcription of a number of genes involved in the cellular response to
      hypoxia. The HIF-1alpha protein is rapidly degraded in cells supplied with
      adequate oxygen but is stabilized in hypoxic cells. Using polysome profile
      analysis, we found that translation of HIF-1alpha mRNA in NIH3T3 cells is spared
      the general reduction in translation rate that occurs during hypoxia. To assess
      whether the 5'UTR of the HIF-1alpha mRNA contains an internal ribosome entry site
      (IRES), we constructed a dicistronic reporter with the HIF-1alpha 5'UTR inserted
      between two reporter coding regions. We found that the HIF-1alpha 5'UTR promoted
      translation of the downstream reporter, indicating the presence of an IRES. The
      IRES had activity comparable to that of the well-characterized c-myc IRES. IRES
      activity was not affected by hypoxic conditions that caused a reduction in cap
      dependent translation, and IRES activity was less affected by serum-starvation
      than was cap-dependent translation. These data indicate that the presence of an
      IRES in the HIF-1alpha 5'UTR allows translation to be maintained under conditions
      that are inhibitory to cap-dependent translation.

PMID- 12006672
TI  - Programmed cell death takes flight: genetic and genomic approaches to gene
      discovery in Drosophila.
AB  - Programmed cell death (PCD) is an essential and wide-spread physiological process
      that results in the elimination of cells. Genes required to carry out this
      process have been identified, and many of these remain the subjects of intense
      investigation. Here, we describe PCD, its functions, and some of the consequences
      when it goes awry. We review PCD in the model system, the fruit fly, Drosophila
      melanogaster, with a particular emphasis on cell death gene discovery resulting
      from both genetics and genomics-based approaches.

PMID- 12006673
TI  - Expression profiling reveals metabolic and structural components of extraocular
      muscles.
AB  - The extraocular muscles (EOM) are anatomically and physiologically distinct from
      other skeletal muscles. EOM are preferentially affected in mitochondrial
      myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and
      pathophysiological properties of EOM have been attributed to their unique
      molecular makeup: an allotype. We used expression profiling to define molecular
      features of the EOM allotype. We found 346 differentially expressed genes in rat
      EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes
      required for efficient, fatigue-resistant, oxidative metabolism were increased in
      EOM, whereas genes for glycogen metabolism were decreased. EOM also showed
      increased expression of genes related to structural components of EOM such as
      vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes
      related to specialized functional roles of EOM such as the embryonic and EOM
      specific myosin heavy chains and genes for muscle growth, development, and/or
      regeneration were increased. The EOM expression profile was validated using
      biochemical, structural, and molecular methods. Characterization of the EOM
      expression profile begins to define gene transcription patterns associated with
      the unique anatomical, metabolic, and pathophysiological properties of EOM.

PMID- 12006674
TI  - A knockout approach indicates a minor vasoconstrictor role for vascular alpha1B
      adrenoceptors in mouse.
AB  - Pharmacological analysis alone has failed to clarify the role of the three
      alpha(1)-adrenoceptor subtypes in modulating vascular tone, due to a lack of
      sufficiently selective antagonists, particularly for the alpha (1B)-adrenoceptor,
      and the complexity when three receptor subtypes are potentially activated by the
      same agonist. We adopted a combined genetics/ pharmacology strategy based on the
      alpha(1B)-adrenoceptor knockout (KO) mouse. The potency of three alpha(1)
      adrenoceptor antagonists vs. phenylephrine was tested in aorta, carotid,
      mesenteric, and caudal isolated arteries from KO and wild-type (WT) mice. In the
      KO mouse the pharmacology became straightforward, showing alpha(1D) in two major
      conducting arteries (aorta and carotid) and alpha(1A) in two distributing
      arteries (mesenteric and caudal). By combining antagonist pharmacology and
      genetics, we provide a simplified analysis of alpha(1)-mediated vasoconstriction,
      demonstrating that alpha(1D) and alpha(1A) are the major subtypes involved in
      vasoconstriction, with a minor but definite contribution from alpha(1B) in every
      vessel.

PMID- 12006675
TI  - Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J
      and NZB/B1NJ inbred mice.
AB  - To investigate the quantitative trait loci (QTL) regulating plasma cholesterol,
      the female progeny of an (SMxNZB/ B1NJ)xNZB/B1NJ backcross were fed an
      atherogenic diet. After 18 wk, plasma total cholesterol and high-density
      lipoprotein cholesterol (HDL-C) was measured. HDL-C concentrations were greater
      in NZB than in SM mice. For standard chow-fed mice, QTL were found near D5Mit370
      and D18Mit34. For mice fed an atherogenic diet, a QTL was found near D5Mit239.
      The QTL for chow-fed and atherogenic-fed mice on chromosome 5 seem to be two
      different loci. We used a multitrait analysis to rule out pleiotropy in favor of
      a two-QTL hypothesis. Furthermore, the HDL-C in these strains was induced by the
      high-fat diet. For inducible HDL-C, one significant locus was found near
      D15Mit39. The gene for an HDL receptor, Srb1, maps close to the HDL-C QTL at
      D5Mit370, but the concentrations of Srb1 mRNA and SR-B1 protein and the gene
      sequence of NZB/B1NJ and SM/J did not support Srb1 as a candidate gene. With
      these QTL, we have identified chromosomal regions that affect lipoprotein
      profiles in these strains.

PMID- 12006676
TI  - Divergent abnormal muscle relaxation by hypertrophic cardiomyopathy and nemaline
      myopathy mutant tropomyosins.
AB  - Mutations in tropomyosin (Tm) have been linked to distinct inherited diseases of
      cardiac and skeletal muscle, hypertrophic cardiomyopathy (HCM), and nemaline
      myopathy (NM). How HCM and NM mutations in nearly identical Tm proteins produce
      the vastly divergent clinical phenotypes of heightened, prolonged cardiac muscle
      contraction in HCM and skeletal muscle weakness in NM is currently unknown. We
      report here a direct comparison of the effects of HCM (A63V) and NM (M9R) mutant
      Tm on membrane-intact myocyte contractile function as assessed by adenoviral gene
      transfer to fully differentiated cardiac muscle cells. Wild-type, and mutant HCM,
      and mutant NM proteins were expressed at similar levels in myocytes and
      incorporated into sarcomeres. Interestingly, HCM mutant Tm produced significantly
      longer contractions by slowing relaxation, whereas NM mutant Tm produced the
      opposite effect of accelerated muscle relaxation. We propose slowed relaxation
      caused by HCM mutant Tm can directly contribute to diastolic dysfunction seen in
      HCM even without secondary cardiac remodeling. Conversely, hastening of
      relaxation by NM mutant Tm may shift the force-frequency relationship in skeletal
      muscle and contribute to muscle weakness seen in NM. Together, these results
      implicate divergent, abnormal "turning off" of muscle contraction as a cellular
      basis for the differential pathogenesis of mutant Tm-associated HCM and NM.

PMID- 12006677
TI  - Neuron-specific expression of human angiotensinogen in brain causes increased
      salt appetite.
AB  - The brain renin-angiotensin system (RAS) has an important role in the regulation
      of cardiovascular function. In the brain, angiotensinogen (AGT) is expressed
      mainly in astrocytes (glia) and in some neurons in regions controlling
      cardiovascular activities. Because of the inability to dissect the functional
      role of astrocyte- vs. neuron-derived AGT in vivo by pharmacological approaches,
      the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and
      fluid and electrolyte balance remains unclear. Therefore, we generated a
      transgenic mouse model overexpressing human AGT under the control of a neuron
      specific (synapsin I) promoter (SYN-hAGT). These mice exhibited high-level
      expression of human AGT mRNA in the brain, with lower expression in the kidney
      and heart. Human AGT was not detected in plasma, but in the brain it was
      expressed exclusively in neurons. Intracerebroventricular (30 ng) but not
      intravenous (500 ng) injection of purified human renin (hREN) caused a pressor
      response, which was prevented by intracerebroventricular preinjection of the
      angiotensin II type 1 receptor antagonist losartan, indicating an AT(1) receptor
      dependent functional role of neuron-derived AGT in the regulation of BP in
      response to exogenous REN. Double transgenic mice expressing both the hREN gene
      and SYN-hAGT transgene exhibited normal BP and water intake but had an increased
      preference for salt. These data suggest that neuronal AGT may play an important
      role in regulating salt intake and salt appetite.

PMID- 12006678
TI  - Heterogeneity of gene expression in human atheroma unmasked using cDNA
      representational difference analysis.
AB  - The rupture of an atherosclerotic plaque can have profound consequences, such as
      myocardial or cerebrovascular infarction. The complex interactions of vascular
      smooth muscle cells (VSMCs) with inflammatory and immune cells are thought to
      contribute to both plaque genesis and stability. Key to our understanding of
      these processes is the identification of genes expressed in human atheromatous
      lesions. We have employed cDNA representational difference analysis (RDA) to
      investigate the differences in gene expression between normal and atherosclerotic
      human vessels. Thirty-one cDNA clones representing sequences expressed in
      atheroma were isolated, many of which encoded components of inflammatory and
      immune pathways. The reciprocal experiment, to identify genes expressed in the
      healthy vasculature, identified two genes associated with the contractile
      functions of VSMCs. Semiquantitative RT-PCR analysis of expression of these genes
      in forty samples, derived from healthy and atheromatous vessels, demonstrated
      marked heterogeneity of gene expression between lesions, although several of the
      genes were preferentially expressed in atherosclerotic lesions. In situ
      hybridization identified subsets of macrophages at sites of neovascularization
      within the lesion and intimal VSMCs as expressing the disease-associated genes.
      In conclusion, cDNA RDA is a useful, fast, and efficient technique for studying
      differential gene expression particularly when clinical material is limiting.

PMID- 12006679
TI  - RSNA Board of Directors develops a 3-year strategic plan.

PMID- 12006681
TI  - Leukodystrophy in children: a pictorial review of MR imaging features.
AB  - Dysmyelinating diseases, or leukodystrophies, encompass a wide spectrum of
      inherited neurodegenerative disorders affecting the integrity of myelin in the
      brain and peripheral nerves. Most of these disorders fall into one of three
      categories-lysosomal storage diseases, peroxisomal disorders, and diseases caused
      by mitochondrial dysfunction-and each leukodystrophy has distinctive clinical,
      biochemical, pathologic, and radiologic features. Magnetic resonance (MR) imaging
      has become the primary imaging modality in patients with leukodystrophy and plays
      an important role in the identification, localization, and characterization of
      underlying white matter abnormalities in affected patients. MR imaging has also
      been extensively used to monitor the natural progression of various white matter
      disorders and the response to therapy. Although the MR imaging features of
      leukodystrophy are often nonspecific, systematic analysis of the finer details of
      disease involvement may permit a narrower differential diagnosis, which the
      clinician can then further refine with knowledge of patient history, clinical
      testing, and metabolic analysis.

PMID- 12006682
TI  - Pharmacologic interventions in nuclear radiology: indications, imaging protocols,
      and clinical results.
AB  - Nuclear radiology is valuable in assessing pathophysiology of a variety of organ
      systems. Pharmacologic interventions are often employed in radionuclide imaging
      to monitor the physiologic changes, which in turn facilitate the diagnosis.
      Metoclopramide, erythromycin, and cisapride have been used for gastric emptying
      studies. To overcome false-negative results, cimetidine, pentagastrin, and
      glucagon have been used in imaging of Meckel diverticula. Pharmacologic
      intervention with either cholecystokinin-8 or morphine is used primarily for the
      assessment of diseases of the gallbladder, common bile duct, and sphincter of
      Oddi. Pharmacologic interventions performed during renography include diuretic
      administration, angiotensin-converting enzyme inhibition, and aspirin renography.
      Recombinant thyrotropin can be used in patients with previously treated thyroid
      carcinoma who require lifelong follow-up for recurrent disease. Cardiac
      pharmacologic stress agents fall into two categories: coronary vasodilating
      agents, such as dipyridamole and adenosine, and cardiac positive inotropic
      agents, such as dobutamine and arbutamine. Measurement of hemodynamic responses
      to pharmacologic flow augmentation with carbon dioxide or acetazolamide is
      valuable in cerebrovascular perfusion studies.

PMID- 12006683
TI  - Lymphoscintigraphy in cutaneous melanoma: a total body atlas of sentinel node
      mapping.
AB  - Lymphoscintigraphy of malignant melanoma has been a reliable method of
      identifying regional lymph nodes at risk for metastases and is now considered
      part of the standard of care in patients with melanoma. The status of the
      sentinel lymph node (SLN) is predictive of the metastatic status of the
      corresponding regional lymph node group. Lymphatic channel mapping allows
      identification of the SLN, thereby making selective lymph node sampling possible.
      Consequently, SLN identification with lymphoscintigraphy results in both less
      extensive surgery and more efficient pathologic examination of the lymph node
      specimens. Therefore, it is imperative that radiologists and nuclear medicine
      physicians know which radiopharmaceuticals to use, recognize different lymphatic
      drainage patterns from various primary tumor sites throughout the body, use
      proper imaging techniques, and recognize potential pitfalls in image
      interpretation.

PMID- 12006684
TI  - Percutaneous nephrostomy with extensions of the technique: step by step.
AB  - Minimally invasive therapy in the urinary tract begins with renal access by means
      of percutaneous nephrostomy. Indications for percutaneous nephrostomy include
      urinary diversion, treatment of nephrolithiasis and complex urinary tract
      infections, ureteral intervention, and nephroscopy and ureteroscopy. Bleeding
      complications can be minimized by entering the kidney in a relatively avascular
      zone created by branching of the renal artery. The specific site of renal entry
      is dictated by the indication for access with consideration of the anatomic
      constraints. Successful percutaneous nephrostomy requires visualization of the
      collecting system for selection of an appropriate entry site. The definitive
      entry site is then selected; ideally, the entry site should be subcostal and
      lateral to the paraspinous musculature. Small-bore nephrostomy tracks can be
      created over a guide wire coiled in the renal pelvis. A large-diameter track may
      be necessary for percutaneous stone therapy, nephroscopy, or antegrade
      ureteroscopy. The most common extension of percutaneous nephrostomy is placement
      of a ureteral stent for treatment of obstruction. Transient hematuria occurs in
      virtually every patient after percutaneous nephrostomy, but severe bleeding that
      requires transfusion or intervention is uncommon. In patients with an obstructed
      urinary tract complicated by infection, extensive manipulations pose a risk of
      septic complications.

PMID- 12006685
TI  - Mesenteric venous thrombosis: diagnosis and noninvasive imaging.
AB  - Mesenteric venous thrombosis is an uncommon but potentially lethal cause of bowel
      ischemia. Several imaging methods are available for diagnosis, each of which has
      advantages and disadvantages. Doppler ultrasonography allows direct evaluation of
      the mesenteric and portal veins, provides semiquantitative flow information, and
      allows Doppler waveform analysis of the visceral vessels; however, it is operator
      dependent and is often limited by overlying bowel gas. Conventional contrast
      material-enhanced computed tomography (CT) allows sensitive detection of venous
      thrombosis within the central large vessels of the portomesenteric circulation
      and any associated secondary findings; however, it is limited by respiratory
      misregistration, motion artifact, and substantially decreased longitudinal
      spatial resolution. Helical CT and CT angiography, especially when performed with
      multi-detector row scanners, and magnetic resonance (MR) imaging, particularly
      gadolinium-enhanced MR angiography, enable volumetric acquisitions in a single
      breath hold, eliminating motion artifact and suppressing respiratory
      misregistration. Helical CT angiography and three-dimensional gadolinium-enhanced
      MR angiography should be considered the primary diagnostic modalities for
      patients with a high clinical suspicion of mesenteric ischemia. Conventional
      angiography is reserved for equivocal cases at noninvasive imaging and is also
      used in conjunction with transcatheter therapeutic techniques in management of
      symptomatic portal and mesenteric venous thrombosis.

PMID- 12006686
TI  - Emphysematous infections of the abdomen and pelvis: a pictorial review.
AB  - Emphysematous (gas-forming) infections of the abdomen and pelvis represent
      potentially life-threatening conditions that require aggressive medical and often
      surgical management. The initial clinical manifestation of these entities may be
      insidious, but rapid progression to sepsis will occur in the absence of early
      therapeutic intervention. Conventional radiography and ultrasonography are often
      the initial imaging modalities used to evaluate patients with abdominopelvic
      complaints. However, when a differential diagnosis remains, or if further
      localization or confirmation of tentative findings is needed, computed tomography
      (CT) should be considered the imaging modality of choice. CT is both highly
      sensitive and specific in the detection of abnormal gas and well suited to
      reliable depiction of the anatomic location and extent of the gas. Of equal
      importance may be the capability of CT to help reliably identify benign sources
      of gas, because treatment (if any) varies dramatically depending on the source.
      Knowledge of the pathophysiologic characteristics, common predisposing
      conditions, and typical imaging features associated with gas-forming infections
      of the gallbladder, stomach, pancreas, and genitourinary system will help make
      early diagnosis and successful treatment possible. In addition, such knowledge
      will aid in further diagnostic work-up, surveillance of potential complications,
      and evaluation of therapeutic response.

PMID- 12006687
TI  - Fast MR imaging in obstetrics.
AB  - Ultrasonography (US) is the initial imaging modality of choice for evaluation of
      patients in obstetrics. However, the results of US are not always sufficient.
      Magnetic resonance (MR) imaging, which uses no ionizing radiation, may be an
      ideal method for further evaluation. Although MR imaging is not recommended
      during the first trimester and use of contrast material is not recommended in
      pregnant patients, fast MR imaging is useful in various obstetric settings and
      can provide more specific information with excellent tissue contrast and
      multiplanar views. In pregnant patients with acute conditions, various diseases
      (eg, red degeneration of a uterine leiomyoma) may be diagnosed. MR imaging allows
      characterization of pelvic masses discovered during pregnancy and diagnosis of
      postpartum complications (eg, abscess, hematoma, ovarian vein thrombosis). In
      pregnant patients with hydronephrosis, MR urography can demonstrate the site of
      obstruction and the cause (eg, a ureteral stone). MR pelvimetry may be beneficial
      in cases of breech presentation. Contrast material-enhanced dynamic MR imaging
      allows one to evaluate the vascularity of a placental polyp, detect the viable
      component of a gestational trophoblastic tumor, and diagnose a uterine
      arteriovenous malformation. MR imaging enables diagnosis of rare forms of ectopic
      pregnancy and early diagnosis of ectopic pregnancy.

PMID- 12006689
TI  - Contrast-enhanced MR angiography of the hand.
AB  - Contrast material-enhanced magnetic resonance (MR) angiography of the hand
      noninvasively provides information comparable to that provided by conventional
      angiography. It is a quick and easy examination that takes less than 5 minutes to
      perform and produces high-quality images with use of a dedicated surface coil
      that provides a high signal-to-noise ratio, allowing small pixel size and high
      spatial resolution. Contrast-enhanced MR angiography requires intravenous
      injection of gadopentetate dimeglumine and acquisition of a volumetric slab of
      image data from the hand. This information is then projected with a maximum
      intensity-projection algorithm. The technique is generally robust with
      reproducible findings. Image interpretation requires an understanding of (a) the
      normal vascular anatomy and anatomic variants of the hand and (b) common vascular
      diseases. MR angiography of the hand is commonly used to create an arterial "road
      map" prior to surgery, manage traumatic transection, and identify emboli.
      Vascular malformations are readily identified and connective tissue disorders
      including vasculitis are well demonstrated with this technique, which can also be
      used to assess bone viability following trauma to the carpus or to evaluate the
      viability of vascularized bone. Common artifacts may be secondary to contracture
      deformities or "wraparound" effect. However, most potential pitfalls can be
      avoided by being vigilant.

PMID- 12006690
TI  - Unusual primary lung tumors: a radiologic-pathologic overview.
AB  - Although the great majority of lung carcinomas are histologically characterized
      as adenocarcinoma, squamous cell carcinoma, large cell undifferentiated
      carcinoma, or small cell carcinoma, a variety of rare benign and malignant lung
      tumors may sporadically affect the lung. Several nonneoplastic tumorlike lesions
      are seen infrequently but are also part of the differential diagnosis for lung
      masses. Conventional radiographic findings, although of limited value in the
      diagnosis of these entities, should be examined carefully when lung tumors are
      suspected. Computed tomography (CT) is well suited for making a definitive
      diagnosis of some disease processes. CT helps determine the location and features
      of the lesions and depicts associated findings to help document the extent of
      disease. The differential diagnosis can be narrowed when there are typical CT
      features (eg, the presence of fat in lipoid pneumonia). Although unusual primary
      lung tumors are difficult to diagnose on the basis of imaging findings alone
      because such findings are nonspecific in the majority of cases, cross-sectional
      imaging can play an important role in the diagnostic work-up of these unusual
      tumors by delineating their extent and directing the radiologist or
      bronchoscopist to the appropriate biopsy site.

PMID- 12006691
TI  - Primary thoracic sarcomas.
AB  - Primary sarcomas of the thorax are rare. The diagnosis is established only after
      sarcomalike primary lung malignancies and metastatic disease have been excluded.
      Primary sarcomas of the thorax are classified according to their histologic
      features and constitute a large group of tumors that occur in the lung,
      mediastinum, pleura, and chest wall. Angiosarcoma, leiomyosarcoma,
      rhabdomyosarcoma, and mesothelioma (sarcomatoid variant) are the most common
      primary intrathoracic sarcomas. Ewing sarcoma, primitive neuroectodermal tumor,
      chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, synovial sarcoma,
      and fibrosarcoma usually arise in the chest wall. Although primary thoracic
      sarcomas commonly manifest as large, heterogeneous masses, they have a wide
      spectrum of radiologic manifestations, including solitary pulmonary nodules,
      central endobronchial tumors, and intraluminal masses within the pulmonary
      arteries. The different histologic types of sarcomas are frequently
      indistinguishable at radiologic analysis. However, differences in clinical
      presentation and the location of the tumor, as well as morphologic features such
      as calcification within the mass and rib involvement, can be useful in suggesting
      the appropriate diagnosis. For example, a large rib mass in a child with fever
      and malaise indicates a Ewing sarcoma, a mass with a calcified matrix is likely a
      chondrosarcoma or osteosarcoma, and a pulmonary artery mass is likely a
      leiomyosarcoma.

PMID- 12006692
TI  - Diagnosis of arrhythmogenic right ventricular dysplasia: a review.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disorder of
      primarily the right ventricle, with unknown cause and prevalence and with a
      frequent familial occurrence. The typical clinical manifestation consists of
      ventricular arrhythmias with a left bundle branch block (LBBB) pattern that occur
      predominantly in young adults. ARVD may result in sudden death. Other
      manifestations are electrocardiographic repolarization and depolarization
      changes, structural abnormalities that range from subtle wall aneurysms within
      the so-called "triangle of dysplasia" to biventricular regional or global
      dysfunction, and localized or widespread fibrofatty infiltration of the right
      ventricular myocardium. The diagnosis of ARVD is based on the presence of major
      and minor criteria encompassing genetic, electrocardiographic, pathophysiologic,
      and histopathologic factors. The imaging modalities used to evaluate right
      ventricular abnormalities include conventional angiography, echocardiography,
      radionuclide angiography, ultrafast computed tomography, and magnetic resonance
      (MR) imaging. Among these techniques, MR imaging allows the clearest
      visualization of the heart. Because MR imaging depicts both functional and
      structural abnormalities, positive MR imaging findings should be used as
      important additional criteria in the clinical diagnosis of ARVD. MR imaging
      appears to be the optimal technique for detection and follow-up of clinically
      suspected ARVD.

PMID- 12006694
TI  - Cardiovascular flow measurement with phase-contrast MR imaging: basic facts and
      implementation.
AB  - Phase-contrast magnetic resonance (MR) imaging is a well-known but undervalued
      method of obtaining quantitative information on blood flow. Applications of this
      technique in cardiovascular MR imaging are expanding. According to the sequences
      available, phase-contrast measurement can be performed in a breath hold or during
      normal respiration. Prospective as well as retrospective gating techniques can be
      used. Common errors in phase-contrast imaging include mismatched encoding
      velocity, deviation of the imaging plane, inadequate temporal resolution,
      inadequate spatial resolution, accelerated flow and spatial misregistration, and
      phase offset errors. Flow measurements are most precise if the imaging plane is
      perpendicular to the vessel of interest and flow encoding is set to through-plane
      flow. The sequence should be repeated at least once, with a high encoding
      velocity used initially. If peak velocity has to be estimated, flow measurement
      is repeated with an adapted encoding velocity. The overall error of a phase
      contrast flow measurement comprises errors during prescription as well as errors
      that occur during image analysis of the flow data. With phase-contrast imaging,
      the overall error in flow measurement can be reduced to less than 10%, an
      acceptable level of error for routine clinical use.

PMID- 12006696
TI  - Cardiac myxoma: imaging features in 83 patients.
AB  - Eighty-six cardiac myxomas were reviewed retrospectively for the clinical,
      pathologic, and radiologic findings. In this series, 83 patients (47 female and
      36 male; age range, 2-78 years; mean age, 48 years) had 49 left atrial (60%), 23
      right atrial (28%), seven right ventricular (8%), two biatrial, and two cases of
      multifocal myxomas. Seventy-one (88%) patients were symptomatic. Radiographs of
      38 patients with left atrial myxoma showed evidence of mitral valve obstruction
      in 53%; radiographs of 16 patients with right atrial myxoma demonstrated
      calcification and cardiomegaly in 56% and 50%, respectively. Computed tomographic
      (CT) scans of 21 myxomas demonstrated 20 (95%) spherical or ovoid lesions, 16
      (76%) with lobular borders. Seventeen (81%) were hypoattenuated; 14 (67%) were
      heterogeneous. Twenty-eight magnetic resonance (MR) imaging studies of 30 myxomas
      showed 29 (97%) spherical or ovoid lesions; 26 (87%) had lobular contours and 26
      (90%) of 29 had heterogeneous signal intensity on T1-weighted images. Point of
      attachment was visible in 15 (83%) cases. Cine gradient recalled echo (GRE) MR
      images of 10 lesions showed low signal intensity in all cases. Most patients with
      cardiac myxomas have abnormal but usually nonspecific radiographic findings. CT
      demonstrates intracavitary heterogeneous, hypoattenuated lobular masses. MR
      imaging shows heterogeneous lobular lesions and usually allows visualization of
      the point of attachment. Radiologic imaging of these lesions, particularly with
      multiplanar and cine GRE MR imaging, can provide accurate assessment of the size,
      location, and point of attachment of these lesions and should assist in surgical
      planning.

PMID- 12006697
TI  - Best cases from the AFIP: invasive ductal carcinoma with osteoclast-like giant
      cells.

PMID- 12006698
TI  - Special focus session: multisection (multidetector) CT: applications in the
      abdomen.

PMID- 12006699
TI  - Special focus session: multidetector CT: abdominal visceral imaging.
AB  - Multidetector computed tomography (CT) has diffused rapidly into clinical imaging
      practice in a short time. Major improvements in relation to single-detector CT
      are faster image acquisition and improved z-axis resolution. Abdominal visceral
      imaging with multidetector CT uses both the vascular and parenchymal phases of
      contrast material enhancement to provide a combined angiographic and multipass
      organ-directed study. All examinations are performed with standard contrast
      material loads.

PMID- 12006700
TI  - Wireless local area networking for linking a PC reporting system and PACS:
      clinical feasibility in emergency reporting.
AB  - Although local area networks (LANs) are commonplace in hospital-based radiology
      departments today, wireless LANs are still relatively unknown and untried. A
      linked wireless reporting system was developed to improve work throughput and
      efficiency. It allows radiologists, physicians, and technologists to review
      current radiology reports and images and instantly compare them with reports and
      images from previous examinations. This reporting system also facilitates
      creation of teaching files quickly, easily, and accurately. It consists of a
      Digital Imaging and Communications in Medicine 3.0-based picture archiving and
      communication system (PACS), a diagnostic report server, and portable laptop
      computers. The PACS interfaces with magnetic resonance imagers, computed
      tomographic scanners, and computed radiography equipment. The same kind of
      functionality is achievable with a wireless LAN as with a wired LAN, with
      comparable bandwidth but with less cabling infrastructure required. This wireless
      system is presently incorporated into the operations of the emergency and
      radiology departments, with future plans calling for applications in operating
      rooms, outpatient departments, all hospital wards, and intensive care units. No
      major problems have been encountered with the system, which is in constant use
      and appears to be quite successful.

PMID- 12006701
TI  - Molecular genetics of vitamin D- dependent hereditary rickets.
AB  - Vitamin D exerts a wide variety of biological actions. The active form of vitamin
      D, 1alpha,25(OH)(2)D(3), is biosynthesized from cholesterol. The final, critical
      step in this biosynthesis is conversion from 25-hydroxyvitamin D(3) to
      1alpha,25(OH)(2)D(3) by the enzyme 25-hydroxyvitamin D(3) 1alpha
      hydroxylase(CYP27B1)[1alpha(OH)ase]. 1alpha,25(OH)(2)D(3) transcriptionally
      controls the expression of a particular set of target genes mediated through
      nuclear vitamin D receptor(VDR) acting as a ligand-inducible factor. Two types of
      vitamin D-dependent hereditary rickets (VDDR) are known to be caused by mutations
      in the 1alpha(OH)ase and VDR genes. The 1alpha(OH)ase gene is responsible for
      VDDR type I, and VDR for type II. Both of the diseases display an autosomal
      recessive trait, but clinical features and response to administrated
      1alpha,25(OH)(2)D(3) are distinct. The phenotypes of the gene KO mice deficient
      of 1alpha(OH)ase and VDR exhibited the clinical abnormalities observed in the
      VDDR patients.

PMID- 12006702
TI  - Effect of subclinical hypothyroidism and obesity on whole-body and regional bone
      mineral content.
AB  - OBJECTIVE: The present investigation was aimed to evaluate the effect of
      subclinical hypothyroidism and obesity on bone mineral content (BMC) in different
      body segments. METHODS: Thirty-two premenopausal women (age: 37 +/- 9.9 years),
      with a wide range in body mass index (BMI), were studied. Subclinical
      hypothyroidism was defined by a basal TSH > or = 4 microU/l and/or a TRH
      stimulated peak > or = 30 microU/l. For each subject, weight, height, BMI
      (weight/height(2)) and the waist/hip ratio were measured. Total BMC, total bone
      mineral density (BMD), leg BMC, leg BMD, trunk BMC, trunk BMD, arm BMC and arm
      BMD were determined using dual-energy X-ray absorptiometry. Thyroid function
      (basal and TRH-stimulated TSH, free T(3) and free T(4)) were determined from
      fasting blood samples for all subjects. RESULTS: Anova was conducted within all
      the groups to observe the effect of thyroid status and/or obesity on BMC and BMD.
      There was no statistical difference for age. Total BMC was affected by obesity (p
      < 0.05) but not by thyroid status, BMD of the legs was significantly influenced
      both by thyroid function and obesity (p < 0.01); total BMD was affected by
      hypothyroid status (p < 0.05). A direct relationship between leg BMD and TSH was
      demonstrated. CONCLUSION: Subclinical thyroid hypofunction and obesity seem to
      affect BMD differently in the body segments. An influence of gravitational force
      seems necessary in order to make evident the effect of subclinical hypothyroidism
      on bone. A condition of subclinical hypothyroidism should be considered when
      evaluating subjects for osteoporosis, since a BMD measured at the femoral neck
      may induce underestimation of initial osteoporosis.

PMID- 12006703
TI  - Prevalence of hypergastrinemia in patients with hyper- and hypothyroidism: impact
      for calcitonin?
AB  - OBJECTIVES: To evaluate the prevalence of hypergastrinemia in patients with
      hyperthyroidism and hypothyroidism and to determine whether gastrin-induced
      hypercalcitonemia could explain the high prevalence of thyroid C-cell hyperplasia
      among patients with hyperthyroidism. METHODS: Concentrations of gastrin and of
      hCT were determined by commercially available radioimmunoassays. RESULTS:
      Elevated serum concentrations of gastrin were found in 17 of 161 (10.5%) patients
      with manifest hyperthyroidism (Graves' disease) and in 4 of 37 (10.8%) and 23 of
      255 (9.0%) patients with manifest or subclinical hypothyroidism, respectively.
      Only 2 cases of hypergastrinemia of 255 subclinically hypothyroid patients (0.8%)
      could not be linked to thyroid autoimmune disease by either biochemical or
      sonographic criteria. Four patients with Graves' disease presented elevated
      plasma concentrations of calcitonin, but none of these patients also had an
      elevated serum gastrin. CONCLUSIONS: The prevalence of hypergastrinemia in
      autoimmune thyroid disease is about 10%. The determination of gastrin in
      subclinical hypothyroidism is not cost-effective in the absence of biochemical
      and/or sonographic markers of autoimmune thyroid disease. The determination of
      gastrin is of no use to predict the presence of C-cell hyperplasia commonly seen
      in patients with Graves' disease.

PMID- 12006704
TI  - Phenotypic heterogeneity associated with identical mutations in residue 870 of
      the androgen receptor.
AB  - BACKGROUND/AIMS: Mutations in the androgen receptor (AR) gene result in an X
      linked recessive form of male pseudohermaphroditism known as the androgen
      insensitivity syndrome (AIS). The alterations most frequently observed are
      missense or nonsense point mutations in exons 4-8 of the AR gene that affect the
      steroid-binding domain of the receptor in subjects with various degrees of
      androgen resistance. Despite the increasing number of AR mutations identified, a
      reliable genotype-phenotype correlation has not been established and individuals
      with the same molecular defect may exhibit different phenotypes. Here, we studied
      a patients with an AIS characterized by bilateral gynecomastia, normal male
      external genitalia, and normal sperm counts. METHODS: Exon-specific polymerase
      chain reaction, single-stranded conformational polymorphism, and sequencing
      analysis of the subject's AR gene were performed in addition to hormone-binding
      assays in skin fibroblasts from the patient. RESULTS: A point mutation at codon
      870 of the AR, changing alanine to valine, was detected. CONCLUSION: As AR
      missense mutations changing alanine 870 to valine have been previously described
      in 3 unrelated patients showing severe AIS phenotypes, we conclude that
      phenotypic heterogeneity associated to identical mutations in the AR gene is
      probably due to individual functional differences in AR coregulator molecules.

PMID- 12006705
TI  - Functional IL-18 Is produced by primary pancreatic mouse islets and NIT-1 beta
      cells and participates in the progression towards destructive insulitis.
AB  - BACKGROUND: Preclinical stages of type 1 diabetes are characterized by
      infiltrating T cells and by the peri- and intra-islet accumulation of pro
      inflammatory mediators, such as IFNgamma. METHODS/RESULTS: Using quantitative PCR
      we demonstrated that mRNA specific for the IFNgamma-inducing cytokine IL-18 is
      upregulated in NIT-1 beta cells and intact mouse islets upon exposure to IL
      1beta, IFNgamma and TNFalpha. The biological activity of IL-18 was blocked using
      caspase inhibitors and anti-IL-18 antibodies. Increased IL-18 expression was also
      detected in islets during advanced stages of insulitis and correlated with
      elevated transcripts for IFNgamma and for the IL-18 receptor. CONCLUSION: Thus,
      beta cells produce bioactive IL-18 in the course of insulitis and actively
      contribute to the exacerbation of inflammation leading to their own demise.

PMID- 12006706
TI  - Insulin-like growth factors and insulin-like growth factor binding proteins in
      adult patients with severe liver disease before and after orthotopic liver
      transplantation.
AB  - INTRODUCTION: The liver is the main source of serum insulin-like growth factors
      (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins
      might reflect liver function. METHODS: In a retrospective longitudinal study we
      examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3
      and IGFBP-6 in 21 adult patients with end-stage liver disease before and after
      orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each
      patient, the mean value of at least three measurements before and after LTX was
      calculated. RESULTS: Before LTX, serum levels of total and free IGF-I, IGF-II,
      IGFBP-3 were low and showed a rapid and significant increase in almost all
      patients after successful LTX (total IGF-I: 30 +/- 7 vs. 256 +/- 30 ng/ml, p <
      0.001; free IGF-I: 1.3 +/- 0.3 vs. 3.5 +/- 0.6 ng/ml, p < 0.01; IGF-II: 177 +/-
      28 vs. 618 +/- 30 ng/ml, p < 0.001; IGFBP-3: 1,230 +/- 136 vs. 3,665 +/- 264
      ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before
      LTX, and declined to normal levels after LTX (210 +/- 40 vs. 90 +/- 15 ng/ml, p <
      0.01), while IGFBP-2 did not show any significant changes (1,154 +/- 296 vs.
      1,303 +/- 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or
      IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p
      < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and
      prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). CONCLUSION:
      Patients with severe liver disease show decreased levels of total and free IGF-I,
      IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are
      promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and
      IGFBP-3 might be useful parameters for the assessment of liver function.

PMID- 12006707
TI  - Long-Term GH therapy: epidemiology and auxologic outcome.
AB  - OBJECTIVES: Epidemiologic and auxologic characteristics of patients treated with
      GH during childhood and adolescence and entered in a national registry in
      Catalonia were studied between 1988 and 1997. At the end of 1997, prevalence was
      53.2 treatments/100,000 inhabitants aged 0-14 years. Maximum annual incidence
      rates were observed in 1990 and 1991 (34.0-35.6 cases/100,000 inhabitants aged 0
      14 years). STUDY DESIGN: Analysis of treatments terminated in 1993 (n = 548)
      revealed, for the three principal reasons for cessation of treatment ('near-final
      height', 'adequate height but further growth potential', and 'poor growth
      response'), that males began and ended treatment at older ages with a better
      auxologic situation in SDS than girls at the beginning and end of therapy in the
      first two subgroups, with a similar duration of therapy. Severe GH deficiency
      (GHD) [both multiple pituitary hormone deficiency (MPHD) and the most severe
      isolated GHD (IGHD-A)] was more frequent in the group ending treatment at 'near
      final height', whereas cessation of therapy because of 'poor growth response' was
      more frequent in the group with 'other causes of short stature' and no
      demonstrable GHD by routine tests. In the near-final height group, after
      excluding Turner's syndrome, MPHD and GHD cases secondary to brain tumors and GH
      deficiencies associated with malformative syndromes, positive linear correlations
      were observed between HSDS at the end of treatment and HSDS at the beginning,
      predicted adult height SDS (PAHSDS) and target height SDS (THSDS). Multiple
      regression analysis showed that in this group of patients, 41.4% of the
      variability in HSDS increment can be explained by the equation: HSDS increment = 
      0.33 + 0.29 THSDS - 0.68 HSDS at the beginning of treatment. RESULTS: The outcome
      showed a reasonable use of GH, since good-response cases generally continued
      treatment until final height whereas therapy was suspended in doubtful cases.

PMID- 12006708
TI  - Familial combined pituitary hormone deficiency caused by PROP-1 gene mutation.
      Growth patterns and MRI studies in untreated subjects.
AB  - BACKGROUND: Mutations of the prophet of PIT-1 (PROP-1), a paired-like homeodomain
      transcription factor which is responsible for early embryonic pituitary
      development, have recently been reported as a cause of combined pituitary hormone
      deficiency. METHODS: We describe the phenotype, long-term auxological data and
      MRI findings in two families with 4 affected members, all of whom have a mutation
      of the PROP-1 gene. GH, TSH, PRL, LH and FSH were completely deficient in all
      patients. RESULTS: ACTH deficiency was not diagnosed until the 3rd or 4th decades
      of life. Pituitary MRI showed an empty sella in 2 subjects, but unspecific tissue
      accumulation resembling a pituitary mass lesion in another patient. The affected
      boy from family II who was continuously treated with all the necessary hormones
      reached the familial target height. However, the 3 subjects in family I were only
      treated sporadically (GH treatment lasting from 1 to 3 years). CONCLUSION:
      Despite this insufficient therapy, final height was in the lower normal range.
      Longitudinal growth continued up to the age of 40 years in these subjects.

PMID- 12006709
TI  - A rapid, quantitative immunofunctional assay for measuring human leptin.
AB  - BACKGROUND: We have developed a rapid, sensitive and quantitative in vitro assay
      for leptin based upon its ability to bind to the soluble extracellular domain of
      the leptin receptor (sOB-R). Such an assay is theoretically capable of
      differentiating between physiologically active leptin molecules from those with
      modified, either enhanced or reduced, binding activity. METHODS: A preparation of
      sOB-R was immobilized to capture leptin from serum samples or standards. Anti
      leptin antibodies that had been raised in rabbits were added in a second
      incubation step to identify leptin molecules bound to sOB-R. Signal detection was
      performed in a third incubation step by anti-rabbit IgG labeled with peroxidase.
      The immunofunctional assay (IFA) was clinically validated by the comparison of
      leptin levels in adolescents (n = 41, age range 9-18 years, BMI range 13.4-33.8
      kg/m(2) and adults (n = 80, age range 18-77 years, BMI range 16.4-54.7 kg/m(2)
      measured using the IFA with data of an in-house RIA performed with the same
      standards and leptin antibodies. RESULTS: The functional sensitivity of the IFA
      was 0.4 ng/ml and comparable to the data of the RIA. Intra- and interassay
      coefficients of variation were below 12.5 % in both methods. Leptin levels
      correlated well with the BMI of the subjects studied (r = 0.70 for RIA, r = 0.72
      for IFA; p < 0.0001) as well as between IFA (y) and RIA (x) (y = x -1.31 ng/ml; r
      = 0.97, p < 0.0001). The median of the quotient between IFA and RIA levels was
      0.86 (quartile range 0.60-1.10) for all samples. CONCLUSIONS: So far, only at the
      most minor differences between leptin measurements using the newly developed IFA
      and those using a conventional RIA have been detected. Additional studies using
      the IFA method are required to investigate whether or not discrepant results with
      the IFA will be seen in various states of relative leptin resistance and whether
      or not such differences are of biological relevance.

PMID- 12006710
TI  - 17-Hydroxylase/17,20 lyase deficiency diagnosed during childhood.
AB  - We present a case of familial 17alpha-hydroxylase/17,20 lyase (CYP17) deficiency
      in which the index case, a 14-year-old XX girl, led to the diagnosis of the
      condition in a 9-year-old XY sister. No mutations in the CYP 17 gene were found
      in any of the girls.

PMID- 12006711
TI  - A novel thyroid hormone receptor-beta mutation, not anticipated to occur in
      resistance to thyroid hormone, causes variable phenotypes.
AB  - Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable
      tissue hyposensitivity to thyroid hormones and is linked to mutations in the
      thyroid hormone receptor-beta (TRbeta) gene. We report here for the first time in
      vivo the mutation R429W (CCG-->TCG) located in the exon 10. The artificial mutant
      obtained in vitro displayed a normal T(3)-binding affinity and transactivation
      function. Therefore, it was thought to produce little, if any, clinical effect
      and to escape to clinical detection. The present report is at least in part
      discordant with this prediction since the propositus and his grandmother had an
      authentic hyperthyroidism with high FT(4) plasma level in the presence of
      inappropriate TSH. On the other hand, spontaneous variations of clinical features
      and - interestingly - of plasma FT(4) concentrations with time in the propositus,
      and the phenotype observed in his mother who never complained with thyrotoxic
      symptoms, confirmed the in vitro binding and functional predictions. The most
      intriguing is the clinical course of the grandmother as she first presented with
      predominant pituitary RTH and a diffuse goiter and finally with a toxic
      multinodular goiter with normal T(3) and T(4) plasma concentrations and
      suppressed TSH. In conclusion, we report a novel mutation in the gene encoding
      the thyroid hormone receptor responsible for predominant pituitary RTH already
      described in vitro but not in vivo. The fluctuant phenotype of the propositus
      suggests that other factors modulate the degree of tissue resistance that is
      under genetic control. Toxic multinodular goiter, possibly due to chronic TSH
      stimulation during RTH, in addition to the phenotype variability, increases the
      difficulty to diagnose this thyroid disorder.

PMID- 12006712
TI  - Early puberty in adopted children.
AB  - Early puberty is frequently observed in adopted children. In various studies,
      early puberty has been associated with decreased final height. In Europe, studies
      were undertaken to treat early puberty in adopted children with GnRH agonist.
      This article reviews the current understanding of early puberty in adopted
      children, including prevalence, background and treatment options. Data from the
      European studies are briefly described. Besides auxological aspects,
      psychological items are addressed as well. Studies on the psychological effect of
      early puberty in adopted children are reported. Future issues include further
      study in the mechanism of early puberty in adopted children, evaluation of final
      height results of the growth studies and quality of life assessments in this
      specific group of children.

PMID- 12006713
TI  - Inverse correlation between insulin-like growth factor (IGF)-binding protein-5
      and IGF-I and II during postnatal development of the anterior pituitary gland.
AB  - BACKGROUND: The insulin-like growth factor (IGF) system is important for
      pituitary development and control, with each member of this axis having a
      specific temporal and spatial expression. Because IGF-binding protein-5 (IGFBP-5)
      is one of the most highly expressed binding proteins in the anterior pituitary
      (AP), it might be of special importance in this gland. OBJECTIVE: The purpose of
      this study was to examine the temporal relationship between the expression of the
      IGFs and IGFBP-5 in the AP during postnatal development. DESIGN AND METHODS:
      Quantitative reverse transcription polymerase chain reaction was used to study
      the mRNA levels of these proteins in the AP of male and female rats at 10, 20,
      30, 40 and 60 days of age. RESULTS: The highest mRNA levels of IGF-I and II
      occurred at 10 and 20 days of age with a dramatic decrease at 30 days (p <
      0.0001). IGF-I, but not IGF-II, mRNA levels increased again during adulthood (60
      days). The pattern of IGFBP-5 mRNA was inversely expressed, with maximum values
      occurring at 40 days. IGF-I mRNA levels were higher in males at 10 days, but
      higher in females at 20 days. The expression of IGF-II was higher in males both
      at 10 and 20 days. IGFBP-5 gene expression was higher in females at 40 days.
      CONCLUSION: The dramatic changes in the expression of IGF-I, IGF-II and IGFBP-5
      throughout postnatal development suggest that these factors play important roles
      in the development of this gland and that their actions are highly interrelated.

PMID- 12006714
TI  - Differential regulation of insulin-like growth factor-(IGF) I and IGF-binding
      protein (IGFBP) secretion by human peripheral blood mononuclear cells.
AB  - BACKGROUND: Recent studies have shown that immunocompetent cells synthesize and
      express growth hormone (GH), growth hormone receptors (GH-R), insulin-like growth
      factor I (IGF-I), IGF-I receptors (IGF-I-R) and different insulin-like growth
      factor binding proteins (IGFBPs). The aim of the current study was to evaluate
      the regulation of IGFBP and IGF-I secretion from immunocompetent cells by
      different mitogens. METHODS/RESULTS: We studied the in vitro secretion pattern of
      IGFBPs and IGF-I from human peripheral blood mononuclear cells (PBMC), derived
      from 10 normal adults and 8 GH-deficient patients with adult onset. In serum-free
      conditioned medium of unstimulated PBMC, derived from normal adults, Western
      ligand blotting (1D-WLB) revealed a 24-kD, a 34-kD and a 39/43-kD doublet band to
      be most prominent. According to their molecular weight and two-dimensional
      Western ligand blot analysis (2D-WLB), these bands are deglycosylated IGFBP-4,
      IGFBP-2 and IGFBP-3, respectively. When the cells were treated with the T-cell
      mitogen phytohemagglutinin (PHA) (10 microg/ml), a differential stimulation of
      IGFBPs was found with a 2.57 +/- 0.48-fold increase of IGFBP-4 (p < 0.01), a 1.55
      +/- 0.13-fold increase of IGFBP-2 (p < 0.01), and a 1.35 +/- 0.19-fold increase
      of IGFBP-3 (n.s.). In contrast, treatment with the B-cell mitogen pokeweed
      mitogen (PWM) (10 microg/ml) caused only a modest 1.40 +/- 0.07-fold increase of
      IGFBP-4 (p < 0.01). Treatment with rhGH (100 ng/ml) or rhIGF-I (200 ng/ml) caused
      no significant induction of any specific band, respectively. In contrast to the
      secretion pattern of IGFBPs, IGF-I secretion of the PBMC was not stimulated by
      either PHA or PWM, but showed a significant increase after GH incubation (p <
      0.01). A similar differentiated secretion pattern of IGFBPs and IGF-I was also
      observed in the conditioned medium of PBMC, derived from GH-deficient patients.
      CONCLUSION: In summary, at least three different IGFBPs are secreted by human
      PBMC. Secretion of IGFBPs by PBMC is differentially regulated by different
      lymphocyte mitogens. Secretion of IGFBPs by PBMC is independent of GH or IGF-I,
      whereas the secretion of IGF-I is stimulated by GH. PBMC derived from normal
      adults and GH-deficient patients show similar patterns of IGF-I and IGFBPs
      secretion, thus indicating that the paracrine/autocrine IGF-I-IGFBPs interactions
      of the PBMC are not altered by pituitary GH deficiency.

PMID- 12006715
TI  - Longitudinal assessment of pituitary-thyroid axis and adrenal function in preterm
      infants raised by 'kangaroo mother care'.
AB  - OBJECTIVE: To assess whether complete kangaroo mother care (KMC), a skin-to-skin
      contact intervention, would affect longitudinal/developmental patterns of
      hormonal change. METHOD: An open randomized controlled trial was conducted in a
      large tertiary care hospital, comparing KMC and traditional care for newborn
      infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks
      gestational age) infants from this study provided three blood-spot samples on
      filter paper: at randomization (postnatal age 1-5 days), 2 weeks later, and at
      calculated term (41 weeks gestational age). They met a number of additional
      inclusion criteria including discharge from the hospital within the first
      postnatal week. The levels of 17alpha-hydroxy-progesterone (17-OHP), thyroxine
      stimulating hormone (TSH) and thyroxine (T(4)) were assessed by radioimmunoassay.
      Birth weight (<1,800 or > or =1,800 g) and prenatal maternal corticosteroid
      treatment were taken into account in the analysis. INTERVENTIONS: Complete KMC
      includes early discharge, positioning the infant on the parent's chest in an
      upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the
      traditional care group, infants were discharged according to routine hospital
      practice. RESULTS: Levels of 17-OHP and TSH decreased significantly from
      eligibility to calculated term while T(4) levels did not change significantly
      over time. Most importantly, overall, treatment (KMC) did not interact with the
      pattern of physiological change. CONCLUSIONS: Maturation of the pituitary-thyroid
      axis and adrenal function is apparently not compromised by KMC, at least in
      healthy preterm infants.

PMID- 12006716
TI  - Suppression of puberty in girls with short-acting intranasal versus subcutaneous
      depot GnRH agonist.
AB  - BACKGROUND/AIM: Central precocious puberty (CPP) is more common in females than
      in males. During the last few decades a new group of patients with CPP has been
      seen frequently in Northern Europe, namely children adopted from developing
      countries. GnRH analogue preparations, administered either as intranasal spray or
      as depot preparations, are the drugs of choice for inhibiting the release of
      gonadotropins. The aim of this study was to compare the effect of buserelin given
      by intranasal spray with that of the same compound given as a subcutaneous depot
      preparation. METHODS: The study group comprised 46 pubertal girls below the age
      of 9.5 years, adopted from a developing country. During the first 2 years, the
      treatment used was buserelin acetate 300 microg 6 times daily as a nasal spray.
      During the third year the treatment was changed to Suprefact Depot, 6.3 mg, given
      as a subcutaneous implant every 8 weeks. Half of the girls were randomized to
      growth hormone treatment in addition to the pubertal inhibition. RESULTS: GnRH
      provocation tests after 6 weeks, 1 year and 2 years of treatment with intranasal
      GnRH analogue showed suppression of gonadotropin secretion except in 1 case of
      noncompliance. During the third year, when the long-acting depot preparation was
      used, suppression was more pronounced. The peak LH response, especially, was
      considerably lower than during treatment with the nasal spray preparation. In all
      cases the clinical inhibition of puberty was adequate both during the first two
      years and during the third year. CONCLUSION: Even though the clinical suppression
      of puberty was adequate with both modes of administration, the effect of the
      depot preparation, in this study Suprefact Depot, was more pronounced in terms of
      gonadotropin suppression and less dependent on patient compliance.

PMID- 12006717
TI  - Pulsatile gonadotropin-releasing hormone treatment of men with idiopathic
      hypogonadotropic hypogonadism.
AB  - OBJECTIVES/METHODS: To induce testicular growth and spermatogenesis, 11 patients
      with idiopathic hypogonadotropic hypogonadism were treated with long-term
      subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration.
      Three patients had a history of undescended testes. Patients who did not respond
      to therapy with a sufficient increase in serum testosterone or spermatogenesis
      were offered additional injections with hCG or, after discontinuation of GnRH,
      either combined therapy with hCG and hMG or recombinant FSH. RESULTS: During
      treatment testicular volume and serum levels of FSH, LH and testosterone
      increased. Semen analysis revealed the presence of spermatogenesis in 9 of the 11
      patients (8 on GnRH alone and in 1 when hCG/hMG was subsequently instituted), and
      7 pregnancies have resulted thus far. CONCLUSION: Pulsatile GnRH therapy is a
      well-tolerated and effective therapy for the induction of spermatogenesis in some
      men with idiopathic hypogonadotropic hypogonadism. It appears that a significant
      fraction of them should be treated for a minimum of 1-2 years to maximize
      testicular growth and achieve spermatogenesis. Cryptorchidism was a negative
      prognostic factor.

PMID- 12006718
TI  - Assessing insulin resistance: application of a fasting glucose to insulin ratio
      in growth hormone-treated children.
AB  - BACKGROUND: Insulin resistance (IR) is an important risk factor for
      cardiovascular disease and type-2 diabetes mellitus. Therefore simple measures of
      IR have been proposed to screen the at-risk patient. A fasting serum glucose
      (mg/dl) to plasma insulin (microU/ml) ratio (FGIR) of < 7 was recently suggested
      as a screening tool for IR in certain pediatric patients. METHODS: To determine
      the utility of simple indicators of IR, the FGIR of < 7 was applied to a group of
      patients with established risk for IR. The study group was comprised of non
      growth hormone (GH)-deficient patients with Turner syndrome (TS, n = 92) and
      idiopathic short stature (ISS, n = 73) receiving GH. The occurrence of a FGIR of
      < 7 in these cohorts was compared to data from previous publications.
      RESULTS/CONCLUSIONS: The application of a FGIR of < 7 confirmed a rise in IR with
      GH therapy in both groups as well as a higher occurrence in the TS group, rising
      from 22 to 48% between 12 and 24 months of GH therapy. We conclude that simple
      measures of IR such as the FGIR may be useful in screening and following patients
      at risk for IR.

PMID- 12006719
TI  - Expression of the gene for the alpha-subunit of inhibin in human adrenocortical
      tumours.
AB  - BACKGROUND: To determine whether the pathogenesis of human adrenocortical tumours
      is associated with variations of inhibin expression, we assayed the mRNA of the
      alpha-subunit of inhibin in 5 normal adrenals and 48 adrenocortical tumours,
      including 10 paediatric tumours. RESULTS: mRNA of alpha-subunit of inhibin was
      detected in all adrenocortical tissues. It was similarly abundant in the three
      pathological groups of adult tumours (benign, suspect and malignant) and in
      normal adrenal tissues, irrespective of the hormonal pattern. However, in
      paediatric tumours, the levels of the mRNA for the alpha-subunit of inhibin were
      significantly higher than those in adult tumours (p < 0.01). CONCLUSION: Inhibin
      is more abundant in the foetal than in the adult adrenal cortex and therefore
      these data suggest that the paediatric tumours may have a foetal pattern.

PMID- 12006720
TI  - Effects of thyroid hormone on mRNAs of phosphoglycerate mutase subunits in rat
      muscle during development.
AB  - BACKGROUND: We previously showed that triiodothyronine (T3) stimulates muscle
      phosphoglycerate mutase (PGAM) activity and isozyme transition in rat skeletal
      and cardiac muscles. METHODS: The effects of T3 on PGAM types B and M subunit
      expression in rat muscle during development are reported. RESULTS: T3
      administration during the first 21 days of rat life more than doubles type M PGAM
      mRNA levels, but produces minor effects on type B PGAM mRNA levels. The
      antihormone propylthiouracil (PTU) slightly decreases both type B and M mRNA
      levels, but this decrease is not statistically significant. CONCLUSION: Thyroid
      hormone influences PGAM mRNA isozyme levels differently and increases type M
      mRNA.

PMID- 12006721
TI  - Graves' disease presented as painful goiter.
AB  - Pain in the thyroid gland is rarely present in Graves' disease. We describe a 32
      year-old female hyperthyroid Graves' disease patient with an initial
      manifestation of painful goiter. On physical examination, the thyroid gland was
      diffusely enlarged and tender. The laboratory examinations showed high serum
      thyroid hormone and low thyrotropin values. Serum inflammatory markers, including
      C-reactive protein and erythrocyte sedimentation rate, were elevated. Thyroid
      ultrasound revealed multiple focal hypoechoic areas. All these findings gave an
      initial impression of an acute inflammatory and destructive process in the
      thyroid gland. However, subsequent thyroid scintigraphy demonstrated a diffuse
      radioactive iodide uptake pattern with positive serum thyrotropin receptor
      antibodies. Fine-needle aspiration cytology showed only the presence of
      lymphocytes. She was diagnosed as having Graves' disease and was treated with
      propylthiouracil, and prednisolone was given for neck pain. Within a few days,
      the thyroid tenderness dramatically improved, and the erythrocyte sedimentation
      rate progressively normalized. However, follow-up thyroid function tests still
      showed high serum thyroid hormone levels. The possible etiologies of a painful
      thyroid gland in Graves' disease will be discussed.

PMID- 12006722
TI  - 'Suppressed' double adenoma--a rare pitfall in minimally invasive
      parathyroidectomy.
AB  - Since the introduction of a quick intraoperative parathyroid hormone (QPTH)
      assay, complete removal of hyperfunctioning parathyroid tissue can be proven
      during surgery. We report on a scintigraphically and biochemically documented
      patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed
      hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was
      resected by minimally invasive open parathyroidectomy. QPTH measurements
      confirmed complete resection of hyperfunctioning tissue and histology showed a
      tumorous enlarged left lower parathyroid gland. The patient was normocalcemic
      until 1 month after surgery, when serum calcium increased again. A MIBI scan 6
      months after surgery showed no evidence of hyperfunctioning parathyroid tissue.
      After an increase of PTH, a third MIBI scan another 3 months later was performed.
      Increased tracer uptake behind the lower pole of the right thyroid lobe was seen
      and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was
      removed. These findings support the hypothesis that smaller yet abnormal
      parathyroid glands can be suppressed and may become hypersecretory if left in
      situ after surgical removal of the larger gland.

PMID- 12006723
TI  - Light symptoms following a high-dose intentional L-thyroxine ingestion treated
      with cholestyramine.
AB  - Adult exposure to L-thyroxine has a wide range of presentations: most adults
      either do not develop symptoms or only become minimally symptomatic. Appropriate
      treatments after exposure to L-thyroxine have yet to be established. A 26-year
      old woman with a suicidal intention was witnessed to ingest approximately 50 L
      thyroxine tablets, each containing 0.1 mg L-thyroxine (total dose 5 mg).
      Cholestyramine was administered (4 g every 8 h p.o.). Vital signs were monitored
      every 6 h and the hormone levels (L-thyroxine and thyroid-stimulating hormone)
      every 24 h. The thyroxine levels increased, and the thyroid-stimulating hormone
      levels decreased, with a normalization of the L-thyroxine level on postingestion
      day 6. Hypertension, dysrhythmias, and delusions did not appear in our patient.
      Only distal tremor and diaphoresis appeared on day 1 after ingestion.
      Cholestyramine has been used in cases of iatrogenic hyperthyroidism, in patients
      with Graves' disease, and in patients with digoxin intoxications, with good
      responses in all cases and a low incidence of side effects. This case illustrates
      the potential utility of cholestyramine to treat L-thyroxine intoxications.

PMID- 12006724
TI  - Induction of puberty in the hypogonadal girl--practices and attitudes of
      pediatric endocrinologists in Europe.
AB  - The management of children and adolescents with hypogonadism and in particular
      the induction of puberty in the hypogonadal girl is subject to controversy.
      Therefore, under the auspices and through organization of the Drugs and
      Therapeutics Committee of the European Society of Paediatric Endocrinology
      (ESPE), an interactive voting session and workshop was held at the 39th ESPE
      Annual Meeting in Brussels to discuss these topics. Common practice in Europe and
      attitudes of pediatric endocrinologists in Europe were questioned and recorded in
      the 1.5-hour program. We now report on some of the results of the questionnaires
      and discussions of that session to further the discussion on and knowledge of
      current concepts of induction of puberty in the hypogonadal girl in Europe. It
      became clear from the data accumulated here that the start of treatment, the aims
      of therapy and the modalities of how to treat the hypogonadal girl vary amongst
      pediatric endocrinologists in Europe. For example, a chronological age > or =11
      years was considered appropriate for the start of estrogen therapy by 40.4% (out
      of 188 answers), while 47.8 and 7.5% felt that a chronological age > or =13 and >
      or =15 years respectively was appropriate. In respect to the form and route of
      estrogen administration, the audience was asked for their common estrogen
      replacement practice: 31.9% used oral 17beta-estradiol treatment, while 10% would
      prescribe 17beta-estradiol transdermal patches. Another 12.2% would recommend
      conjugated estrogens (e.g. Premarin) orally, 4.8% use oral estradiol valerate and
      39.3% ethinylestradiol orally. Only 1.8% out of 229 physicians answering were
      undecided. In addition, counseling of patients and their families is quite
      variable and perceptions for example regarding potential pregnancies in affected
      women are also not uniform. In this report the authors do not want to provide
      their own personal views but rather reflect current practice in Europe. It is
      hoped that a more uniform picture will emerge once European and international
      guidelines on how to treat the girl with hypogonadism will be available and even
      more discussions amongst doctors from different countries have been led.

PMID- 12006725
TI  - [Treatment of chronic bronchitis with ivy leaf special extract--multicenter post
      marketing surveillance study in 1,350 patients].
AB  - BACKGROUND AND OBJECTIVES: The changes of clinical symptoms and the tolerability
      of Prospan((R)) acute Effervescent Cough Tablets were investigated in a
      multicenter, prospective post-marketing surveillance (PMS) study focusing on
      patients with chronic bronchitis. PATIENTS AND METHODS: The study included 1,350
      male and female patients aged 4 years and above who were treated in one of 135
      participating medical practices and who suffered from chronic bronchitis (with or
      without airway obstruction). During a scheduled observational period of 4 weeks,
      the patients had to take 1(1/2) or 2 tablets per day (depending on their age),
      according to the manufacturer's dosing recommendations, corresponding to 97.5 or
      130 mg of dried ivy leaf extract (about 585- 780 mg of drug). Treatment success
      was assessed by observing the changes in the direct symptoms of chronic
      bronchitis between the baseline examination and the end of treatment. Safety was
      evaluated by analyzing adverse events. RESULTS: In comparison to baseline, the
      following percentages of patients showed improved symptoms or were cured at
      treatment end: cough 92.2%; expectoration 94.2%; dyspnea 83.1%; respiratory pain
      86.9%. In each of the four symptoms at least 38% of the initially affected
      patients were completely free of complaints. Three patients (0.2%) experienced
      adverse events in which a causal relationship to the drug under investigation
      could not be excluded (2x eructation, 1x nausea). CONCLUSIONS: Considering the
      favorable changes in all investigated clinical symptoms as well as the excellent
      tolerability in children and adults, the ivy leaf extract preparation Prospan
      acute Effervescent Cough Tablets can be considered as a therapeutic option in
      alleviating the symptoms of chronic bronchitis.

PMID- 12006726
TI  - [New findings about Priessnitz from the unknown Vinzenz Priessnitz Familien
      Wasserbuch from 1847].
AB  - The large scope of therapies that Priessnitz used for his cure treatments in
      Grafenberg completely fell into oblivion. More than 50 different applications of
      water, partly created by Priessnitz, dietary therapy for every patient, a lot of
      physical exercise, air as well as sun baths, improvement of fitness, and a
      regular life style were included in Priessnitz' treatments. He treated a variety
      of indications, not only chronic but also severe acute ones. The Vinzenz
      Priessnitz'sche Familien-Wasserbuch is a real treasury of forgotten facts about
      the genius who was the first to rediscover and remodel hydrotherapy before
      Kneipp.

PMID- 12006727
TI  - A non-randomised pilot study to compare complementary and conventional treatments
      of acute sinusitis.
AB  - BACKGROUND: It is still under discussion whether antibiotics are effective in the
      treatment of acute sinusitis. Moreover, they are known to have considerable side
      effects. In contrast, complementary approaches are reported to have little side
      effects and an equivalent efficiency. OBJECTIVES: To assess the success of
      conventional and complementary treatments of acute sinusitis and to estimate the
      patient numbers needed to confirm therapeutic equivalence. Treatment success was
      measured by three different scores, assessed by both patients and physicians.
      METHODS: Multicentre (2 complementary and 3 conventional ENT centres), non
      randomised, controlled clinical trial with 63 patients (complementary group 30,
      conventional group 33 patients). To control for confounders treatment differences
      were estimated by propensity score techniques. TREATMENTS: The choice of
      medication was entirely left to the physician. We recommended to use antibiotics,
      secretolytics and symptomimetics in the conventional group and a combination of
      the herbal remedy Sinupret((R)) and the homeopathic remedy Cinnabaris 3X in the
      complementary group. RESULTS: Treatment differences varied substantially
      depending on the outcome measure, but they were always not clinically relevant.
      Conventional treatment was slightly better when the outcome was assessed by the
      physicians (1.8 score points) but slightly worse when it was assessed by patients
      (0.2 score points) or in terms of the HCG-5 quality of life score (0.8 score
      points). p values were always > 0.3. CONCLUSIONS: Both treatments appear to be
      equally effective (or ineffective). Results might be biased because both
      treatment groups differed substantially. Randomised trials including at least 400
      patients are needed to produce valid results.

PMID- 12006728
TI  - An example on the value of non-randomisation in clinical trials in complementary
      medicine.
AB  - BACKGROUND: Randomised clinical trials may in principle show a small external
      validity. Non-randomised clinical trials therefore are sometimes regarded as an
      appropriate alternative when complementary and conventional treatments are
      compared. OBJECTIVES: To assess the value of advanced statistical methods in the
      process of estimating differences between a complementary and a conventional
      treatment of acute sinusitis in a non-randomised clinical trial. METHODS:
      Multicentre, non-randomised, controlled clinical trial comparing 2 complementary
      and 3 conventional ENT centres. Patients were free to choose the physician (and
      hence the therapy). Treatment differences were estimated by controlling for
      confounders in analyses of covariance or by propensity score techniques. RESULTS:
      Most potential confounders (sex, age, life-style parameters) did not have
      significant effects on the choice of therapy. Disease severity and previous ENT
      surgery were the main confounding factors. At study onset they almost cause a
      defined separation of both treatment groups. As a result estimated treatment
      differences vary substantially depending on the chosen statistical model.
      CONCLUSIONS: When comparing complementary and conventional treatments, non
      randomised clinical trials may be misleading. Results may be strongly biased even
      when advanced statistical methods are used. Trials of complex statistical designs
      are needed to give valid results.

PMID- 12006729
TI  - Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine
      receptors in the monkey brain studied with positron emission tomography.
AB  - The effects on the binding to cholinergic and dopaminergic receptors in the brain
      during continuous intravenous infusion of the muscarinic cholinergic receptor
      agonist milameline (CI-979) were studied in the rhesus monkey by means of
      positron emission tomography. Binding to milameline cholinergic receptors was
      quantified using the muscarinic receptor antagonist [(11)C]-N-methyl-4
      piperidinylbenzilate ([(11)C]NMP), and the effects on nicotine receptor binding
      were measured with (S)-[(11)C-methyl]nicotine. Changes in the binding of the D(2)
      dopamine receptor antagonist [(11)C]raclopride were measured as well. The binding
      of [(11)C]NMP increased in most brain regions with the infusion of increasing
      doses of milameline from 0.5 to 10 microg/kg/h. (S)-[(11)C-methyl]nicotine
      binding was unchanged or increased somewhat. Binding of [(11)C]raclopride to the
      D(2) dopaminergic receptors in the striatum of the brain increased by 10 +/- 4%
      following 2 microg/kg/h of milameline. The results suggest a possible action of
      milameline both on presynaptic muscarinic receptor subtypes as well as dopamine
      levels dependent on the receptor reserve of the muscarinic receptor subtypes.

PMID- 12006730
TI  - Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A
      quantitative, comparative study.
AB  - To evaluate whether magnetic resonance imaging (MRI) of white matter changes in
      Alzheimer's disease either under- or overestimates the findings on
      neuropathology. Postmortem MRI and neuropathological examination were performed
      on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a
      specially designed brain slicer, the brains were cut corresponding to the MRI
      images, and stained by Luxol Fast Blue. Quantitative analysis of white matter
      changes on MRI and neuropathology was performed using stereological principles.
      Measures from MRI and pathology were highly correlated (r(2) = 0.71). However,
      pathology showed significantly more extensive changes than did MRI in all cases,
      with a mean of 54% larger areas. The lesions not identified with MRI represented,
      however, only minor changes with lower intensity of myelin staining and with an
      accentuation of the distance between fibres but with preserved axonal network and
      glial cell density.

PMID- 12006731
TI  - Activity level and balance in subjects with mild Alzheimer's disease.
AB  - To clarify if Alzheimer's disease has an impact on activity level and postural
      control, we examined 17 elderly diagnosed with mild Alzheimer's disease (MMSE
      scores 21-29) and 18 age- and gender-matched healthy controls (MMSE scores 27-30)
      using the Frenchay Activities Index, Bergs Balance Scale, Timed Up & Go and
      Walking in a Figure of Eight. Mild AD subjects were less active and had lower
      scores on Bergs Balance Scale, performed Timed Up & Go in longer time and took
      more steps outside the Figure of Eight, as compared to healthy elderly. This
      study shows that motor performance is affected already at mild stages of
      Alzheimer's disease and also that functional performance other than gait may also
      be impaired.

PMID- 12006732
TI  - Clinical efficacy of piracetam in cognitive impairment: a meta-analysis.
AB  - A meta-analysis has been performed including nineteen double blind, placebo
      controlled studies with piracetam in patients suffering from dementia or
      cognitive impairment in the elderly. These studies had as common outcome measure
      a clinical global impression of change, a measure of clinically meaningful
      improvement. The meta-analysis of this global outcome followed the methodology
      set forward by the Cochrane Collaboration. This article describes the studies,
      the patient populations and the methods of data extraction. The results of the
      meta-analysis demonstrate a difference between those individuals treated with
      piracetam and those given placebo, both as significant odds ratio and as a
      favourable number needed to treat. While there may be problems in meta-analyses
      and the interpretation of the statistical results, the results of this analysis
      provide compelling evidence for the global efficacy of piracetam in a diverse
      group of older subjects with cognitive impairment.

PMID- 12006733
TI  - Serum folate levels and subsequent adverse cerebrovascular outcomes in elderly
      persons.
AB  - Recent epidemiologic studies have shown an association between low serum folate
      levels and risk of vascular disease, including stroke and various types of
      vascular cognitive impairment. We examined data from the Canadian Study of Health
      and Aging (CSHA), a population-based, prospective 5-year investigation of the
      epidemiology of dementia among Canadians aged 65+ years. The risk of an adverse
      cerebrovascular event (including vascular dementia, vascular cognitive
      impairment, or fatal stroke) during follow-up, was assessed according to serum
      folate quartiles among subjects with no evidence of dementia at baseline (n =
      369). After adjusting for certain covariates, including cardiovascular disease
      and nutritional indices, education, smoking and baseline cognitive status, the
      risk estimate for an adverse cerebrovascular event associated with the lowest
      folate quartile compared with the highest quartile was OR 2.42 (95% CI 1.04
      5.61). Results from stratified analyses also showed that relatively low serum
      folate was associated with a significantly higher risk of an adverse
      cerebrovascular event among female (OR 4.02, 95% CI 1.37-11.81) but not male (OR
      1.02, 95% CI 0.25-4.13) subjects. Among the total sample, there was a consistent
      trend toward poorer health and cognitive outcomes during follow-up (including
      mortality, cognitive decline and dementia) among those in the lowest folate
      quartile compared with the highest quartile. Low serum folate levels are
      independently associated with a significantly higher risk of an adverse
      cerebrovascular event, including vascular dementia and stroke death, among older,
      cognitively vulnerable persons.

PMID- 12006734
TI  - Effects of stimulus predictability and interstimulus gap on saccades in
      Alzheimer's disease.
AB  - OBJECTIVES: Studies of saccadic eye movement impairment in Alzheimer's disease
      (AD) have largely focused on simple reflexive eye movements and the antisaccade
      task. The effects of manipulating stimulus timing have been little studied.
      METHODS: Fourteen patients with mild to severe AD and 11 age-matched controls
      were studied on the antisaccade task, while latencies on simultaneous, gap and
      predictable tasks were recorded from 11 patients and 11 controls. Dementia
      severity was assessed with the Mini-Mental State Examination. RESULTS: As a
      group, patients' latencies were significantly higher and more variable on the
      simultaneous and gap tasks. Predictable task performance was similar in mean but
      significantly more variable. Grossly anticipatory responses by patients were
      common on the predictable, simultaneous and gap tasks. Exclusion of these from
      subject means revealed that AD patients, when making target-driven saccades,
      demonstrated a gap effect of similar magnitude to normal subjects. Patients made
      significantly fewer correct antisaccades and significantly more reflexive errors
      not followed by a corrective antisaccade than did controls. CONCLUSIONS: The
      frequent presence of grossly anticipatory saccades may reflect dysfunction of
      fixation mechanisms possibly involving projections from frontal lobe to superior
      colliculus. The less frequently seen, marked prolongation of latency may reflect
      changes in posterior parietal mechanisms mediating reflexive saccade generation.
      The presence of the gap effect demonstrates a continued ability to benefit from
      externally controlled stimulus disengagement. Patients' ability to make
      appropriately timed saccades to targets of known locations was particularly
      impaired, but the target sequence itself was at least grossly correctly learned.
      Larger studies may be able to identify clinically distinct populations of AD
      patients.

PMID- 12006735
TI  - Performance on the cognitive abilities screening instrument at different stages
      of Alzheimer's disease.
AB  - The Cognitive Abilities Screening Instrument (CASI) contains nine cognitive
      domains. Its total score has been used to screen for dementia in epidemiological
      studies conducted in the US, Japan and Taiwan, but its usefulness in
      distinguishing different levels of dementia has not been examined. This study was
      conducted to compare CASI scores of patients with Alzheimer's disease (AD) with
      different levels of severity of dementia. The CASI was administered to 475 AD
      patients with mild, moderate or severe dementia according to the Clinical
      Dementia Rating Scale. The patients' scores were compared to the scores of 475
      age-, education- and gender-matched control subjects. More specifically, each
      patient's score, X, was transformed to a z score with reference to the mean and
      SD of the scores of the control group, where z = (X - mean)/SD. Then, the mean of
      the z scores and the percentage of patients with z scores of <-2.0 were compared
      among the three patient groups. For the CASI total score and all of its nine
      domain scores, the mean z score decreased (except that for short-term memory) and
      a higher percentage of patients scored below the normal range with increasing
      severity of dementia. This study validates the usefulness of the CASI for
      assessing the severity of dementia. The domain scores differed in their relative
      usefulness for detecting dementia and for distinguishing in different levels of
      dementia.

PMID- 12006736
TI  - The neurophysiology of auditory perception: from single units to evoked
      potentials.
AB  - Evoked electric potential and magnetic field studies have the immense benefit
      that they can be conducted in awake, behaving humans and can be directly
      correlated with aspects of perception. As such, they are powerful objective
      indicators of perceptual properties. However, given a set of evoked potential
      and/or evoked field waveforms and their source locations, obtained for an
      exhaustive set of stimuli and stimulus contrasts, is it possible to determine
      blindly, i.e. predict, what the stimuli or stimulus contrasts were? If this can
      be done with some success, then a useful amount of information resides in scalp
      recorded activity for, e.g., the study of auditory speech processing. In this
      review, we compare neural representations based on single-unit and evoked
      response activity for vowels and consonant-vowel phonemes with distinctions in
      formant glides and voice onset time. We conclude that temporal aspects of evoked
      responses can track some of the dominant response features present in single-unit
      activity. However, N1 morphology does not reliably predict phonetic
      identification of stimuli varying in voice onset time, and the reported
      appearance of a double-peak onset response in aggregate recordings from the
      auditory cortex does not indicate a cortical correlate of the perception of
      voicelessness. This suggests that temporal aspects of single-unit population
      activity are likely not inclusive enough for representation of categorical
      perception boundaries. In contrast to population activity based on single-unit
      recording, the ability to accurately localize the sources of scalp-evoked
      activity is one of the bottlenecks in obtaining an accessible neurophysiological
      substrate of perception. Attaining this is one of the requisites to arrive at the
      prospect of blind determination of stimuli on the basis of evoked responses. At
      the current sophistication level of recording and analysis, evoked responses
      remain in the realm of extremely sensitive objective indicators of stimulus
      change or stimulus differences. As such, they are signs of perceptual activity,
      but not comprehensive representations thereof.

PMID- 12006737
TI  - Nongenomic effects of corticosteroids on ion transport by stria vascularis.
AB  - Stria vascularis electrogenically secretes potassium into endolymph and this
      secretion is known to be under acute control of several hormone receptors
      including purinergic, adrenergic and muscarinic receptors. Recently, chronic
      application of glucocorticosteroid hormones in autoimmune mice was reported to
      restore both hearing and normal strial morphology. The purpose of this study was
      to investigate the acute nongenomic effects of glucocorticoids and
      mineralocorticoid on the short circuit current (I(sc,probe)) across isolated
      stria vascularis of gerbils using the voltage-sensitive vibrating probe.
      Application of prednisolone (0.1-30 microM) caused an increase of I(sc,probe) in
      a dose-dependent manner with an EC50 of 1.1 +/- 0.2 microM (n = 5).
      Hydrocortisone (10 microM, n = 5) and dexamethasone (10 microM, n = 5) also
      increased I(sc,probe), but the response was transient and the response rate was
      faster than for prednisolone. By contrast, aldosterone (10 microM, n = 6) caused
      a transient decrease of I(sc,probe )within seconds. These results suggest that
      prednisolone increased secretion of K+ via a nongenomic mechanism in the range of
      therapeutic plasma concentrations and that this stimulatory effect of
      glucocorticoids is specific since the mineralocorticoid aldosterone caused a
      distinctly different response.

PMID- 12006738
TI  - Human auditory steady-state responses during repeated exposure to hypobaric
      hypoxia.
AB  - This study was aimed at evaluating the time course of auditory steady-state
      response (SSR) variations during two consecutive exposures to hypobaric hypoxia.
      Six normal subjects were examined in a hypobaric chamber at ground level. Then,
      they climbed to a simulated altitude of 17000 ft (5182 m), where SSRs were
      recorded after 6, 12, 18, 24 and 30 min. Thereafter, they breathed 100% O2 and
      SSRs were recorded after 2 min of reoxygenation. A second exposure to hypoxia
      followed, with SSR recordings after 6 and 12 min. Finally, the subjects returned
      to ground level for recovery recording. A phase shift of SSR sinus wave was
      observed at the beginning of both exposures to hypoxia, although in the first
      recording (i.e. at 6 min) during the first exposure, the result was not
      statistically significant. A slight SSR phase shift was still detectable on
      return to ground level. The central acoustic pathway involved in SSR genesis was
      probably the area which was found to be most sensitive to hypoxia, compared to
      other parts of the auditory apparatus (e.g. the cochlea). This data could suggest
      an impairment of compensation mechanisms when consecutive exposures to hypoxia
      are performed.

PMID- 12006739
TI  - Speech perception and language criteria for paediatric cochlear implant
      candidature.
AB  - Existing criteria for cochlear implantation of children with impaired hearing aim
      to select children who will eventually achieve better speech perception scores
      with an implant than with a hearing aid. It is difficult to predict the eventual
      outcomes with hearing aid and implant because speech perception scores typically
      increase with age, and because the distribution of scores for implant and hearing
      aid users overlap considerably at all ages. This paper shows how speech
      perception scores can be combined with spoken language measures to arrive at an
      objective criterion for implant selection. The method also allows estimation of
      the likely increase in speech perception score within a few months of
      implantation and estimation of the probability that the child will perform better
      with the implant than the hearing aid. The criteria were based on data from 135
      evaluations of 50 children using cochlear implants with monosyllabic words, open
      set sentences, the Clinical Evaluation of Language Fundamentals, and the Peabody
      Picture Vocabulary Test. Data from 114 evaluations of 43 children using hearing
      aids were used to illustrate the sensitivity of the criteria.

PMID- 12006740
TI  - Characteristics of tinnitus induced by acute acoustic trauma: a long-term follow
      up.
AB  - We investigated the prevalence, characteristics and subjective perceived handicap
      caused by long-term tinnitus induced by acute acoustic trauma (AAT) in 418 former
      military conscripts. They had been treated between 1984 and 1989 because of AAT
      from exposure to impulse noise caused by firearm shooting. All 418 patients
      reported tinnitus after the AAT. At discharge from the military service, 122
      (29%) still reported tinnitus. In 1999, of these 122 patients, 101 were reached
      and 66 still had tinnitus. The Tinnitus Handicap Questionnaire demonstrated
      various difficulties in life because of tinnitus, not attributable only to
      tinnitus loudness. Psychological factors also seem to play an important role. The
      effects of AAT and possible compensation have been evaluated so far mostly by
      audiometric findings, but in some cases tinnitus may be an even more serious
      threat to life satisfaction than mild hearing impairment.

PMID- 12006742
TI  - A new classification of the delusional misidentification syndromes.
AB  - In recent years, a great number of very different and in part contradictory
      terminologies and classifications of delusional misidentification syndromes (DMS)
      have been published. In various case reports, several authors have also made
      contradictory comments on questions concerning classification, etiology and
      assignment to a possible entity of DMS. Further development and extension of the
      classifications proposed during recent years did not help to eliminate
      discrepancies and contradictions. The classification presented here has not shown
      any inconsistencies so far and it allows the classification of any DMS that has
      been examined recently.

PMID- 12006743
TI  - An exploratory study on obsessive-compulsive disorder with and without a familial
      component: are there any phenomenological differences?
AB  - Familial studies on obsessive-compulsive disorders (OCD) have suggested that OCD
      is a heterogeneous condition, with some cases being familial and others being
      isolated cases in their families. Nevertheless, no studies evaluated whether
      there are clinical differences between OCD cases with and without a familial
      component. The current report presents data on the prevalence of OCD in first
      degree relatives of OCD probands and compares phenomenological characteristics of
      familial and non-familial OCD types. The family study and the family history
      methods were used to estimate the prevalence of OCD in first-degree relatives of
      74 OCD probands. A statistical comparison between OCD probands with and without
      familial loading was performed using Pearson's chi(2) test, Fisher's exact test,
      or Student's t test when appropriate. The rate of OCD was 3.5% in directly
      interviewed first-degree relatives. Eleven percent of the probands had at least
      one family member with OCD. There were no differences between the two types of
      OCD (familial vs. non-familial) except for life events prior to the onset of OCD,
      which were more common and more severe in non-familial OCD subtypes. In
      conclusion, our results (1) confirm that there is a familial component in the
      expression of some forms of OCD and (2) indicate that familial OCD patients are
      not characterized by peculiar clinical features, but appear to have a lower
      threshold for precipitating events.

PMID- 12006744
TI  - Depersonalization and basic symptoms in schizophrenia.
AB  - The purpose of this study is to examine the classic psychopathologic notion of
      depersonalization in the light of the Basic Symptom paradigm. A sample of 57
      chronic schizophrenics was cross-sectionally assessed with the Bonn Scale for the
      Assessment of Basic Symptoms (BSABS) and contextually with specific scales
      testing positive, negative, depressive and alexithymic dimensions. In order to
      categorize depersonalized vs. nondepersonalized patients three specific BSABS
      items explicitly identifying the allo-/auto-/somatopsychic domains of
      depersonalization were used, according to the wernickian threefold definition.
      Depersonalized schizophrenics showed a semiological profile that was distinct
      from that of nondepersonalized schizophrenics (as regards basic, positive,
      depressive symptoms and alexithymia); patients with multiple co-occurring forms
      of depersonalization revealed higher levels of cognitive disturbance, lowering of
      stress threshold and greater alexithymia. Clinical and research implications are
      discussed.

PMID- 12006745
TI  - Schizophrenics show a failure in the decoding of violations of conversational
      implicatures.
AB  - OBJECTIVES: Recent approaches to the 'theory of mind' and pragmatics support
      that, if we did not have any idea about what other people know, we could hardly
      use language effectively. Successful communication (the pragmatic aspect of
      language) depends on inferring the beliefs and intentions of the partner in the
      conversation. Such successful communication is linguistically realized in part by
      cohesion and in part by abiding by the maxims derived from the cooperative
      principle. However, the violations of the Gricean implicatures are generally used
      in everyday language, mainly to point at a hidden, most commonly negative opinion
      on others. We hypothesize that schizophrenics have difficulties in the decoding
      of these violations, as the core deficit in this disorder is around social
      cognition, theory of mind and pragmatic language use. MATERIAL AND METHOD: We
      have examined 26 paranoid schizophrenic patients and 26 normal control subjects
      by using 4 'question and answer' vignettes, where the Gricean maxim of relevance
      was violated to express a hidden, negative opinion by one partner during the
      communicative act. The subjects were asked to judge these opinions and were
      evaluated by the investigators on a score from 0 to 2 points. In a pilot study,
      interrater reliability was judged to be satisfactory. The data were analysed
      statistically by parametric and non-parametric tests. RESULTS: Statistical
      analyses of our data have shown that schizophrenics made significantly more
      mistakes during the decoding of the violated maxim as compared with controls (p <
      0.0001), reflecting on the difficulties during the correct exploration of the
      social context, i.e. recognition of the speaker's hidden opinion. CONCLUSION: We
      conclude that patients with schizophrenia fail to decode intentional violations
      of conversational implicatures. These results point at a dysfunctional pragmatic
      language use among schizophrenic patients.

PMID- 12006746
TI  - Is there a gender difference in a factorial structure of the positive and
      negative syndrome scale? A test by structural equation modeling.
AB  - By means of the multisample structured means strategy, we examined gender
      differences in a five-factorial structure model of Positive and Negative Syndrome
      Scale (PANSS) ratings of 308 patients of both sexes with DSM-IV schizophrenia
      with comparable age at investigation and overall symptomatic severity across sex.
      The test indicated that the factors and component symptoms were common across
      sex, whereas the factor loadings might be different. However, the model that
      incorporated the difference in the factor loadings did not improve model fit
      indices. Therefore, it is concluded that this investigation elicited only minimal
      gender differences, and on the whole confirmed the PANSS five-factor structure
      for both sexes.

PMID- 12006747
TI  - Comparison of psychiatric ICD-10 diagnoses in Denmark and Germany.
AB  - A dataset of psychiatric ICD-10 diagnoses from the Danish case register
      concerning psychiatric hospitals was compared with a sample of psychiatric
      diagnoses from 27 psychiatric hospitals in Germany. The comparison shows a higher
      proportion of F1 diagnoses in the German dataset and a difference in the coding
      of alcohol dependence and harmful use. Some further differences in the groups F0
      F6 are demonstrated and some of them are discussed. The most frequent diagnoses
      found in both datasets but in different sequence are alcohol dependence syndrome
      and paranoid schizophrenia and, in third place, adjustment disorder. Various
      aspects of the problem of rarely used diagnoses are discussed.

PMID- 12006748
TI  - Coping measurement and the state effect of depression and anxiety in psychiatric
      outpatients.
AB  - The relationship between coping styles and mental health has received
      considerable attention, but the state effects on coping measures in a clinical
      sample are not well known. This study investigated changes in scores on the
      Coping Inventory for Stressful Situations between two treatment phases (acute and
      remitted phase) in 49 outpatients with major depression or anxiety disorders.
      Task-oriented coping changed significantly between the treatment phases in both
      depressive and anxious patients, as analyzed by two-way multivariate analysis of
      variance. Results from repeated measures of multivariate analysis of covariance
      indicated that task-oriented coping was influenced by depression and emotion
      oriented coping was influenced by anxiety. Avoidance-oriented coping did not
      change significantly over time in either depressive or anxiety disorders
      controlled for depressive and anxiety symptoms. The results of this study suggest
      that depressive or anxiety symptoms and treatment phase affect coping
      measurement.

PMID- 12006749
TI  - Delusional hermaphroditism: a rare variant of delusional misidentification
      syndrome.
AB  - Since the historical contribution of Capgras and Reboul-Lachaux, several
      researchers began exploring various dimensions of the fascinating phenomena of
      delusional misidentification syndromes. Recently, Mulholland and O'Hara have
      reported a new variant of delusional misidentification syndromes named
      'delusional hermaphroditism'. In this study, we report another case of this rare
      entity.

PMID- 12006750
TI  - What is the ideal initial valve pressure setting in neonates with
      ventriculoperitoneal shunts?
AB  - In order to determine the optimal valve pressure setting during the first weeks
      in neonates after implantation of programmable Hakim valves and to analyze the
      benefits and possible side effects of a new treatment protocol in this age group,
      we performed this prospective study. In 20 consecutive newborns less than 5 weeks
      of age with hydrocephalus due to various etiologies, a ventriculoperitoneal shunt
      with a programmable Hakim valve at an extremely low initial valve pressure
      setting of 30-40 mm H(2)O was implanted. This "overdrainage" was maintained,
      monitored by regular clinical examination and transcranial ultrasonographic
      imaging, until the wound healing was uneventfully completed and the permanent
      valve pressure setting of 100-120 mm H(2)O was chosen. In this age group, which
      is prone to specific noninfectious shunt complications like wound breakdown,
      cerebrospinal fluid (CSF) fistula and subcutaneous CSF collections, none of these
      complications were seen, nor were there any persisting overdrainage phenomena on
      transcranial ultrasonography. Initial, temporary "overdrainage" represents a
      simple, useful and risk-free therapy in neonates with programmable shunts which
      might lower the incidence of typical noninfectious complications in this age
      group.

PMID- 12006751
TI  - A single-incision laparoscopic technique for retrieval and replacement of
      disconnected ventriculoperitoneal shunt tubing found in the peritoneum.
AB  - A 7-year-old girl presented with signs and symptoms of increased intracranial
      pressure 2 years after insertion of a ventriculoperitoneal (VP) shunt. Evaluation
      revealed disconnection of the distal shunt catheter and migration into the
      peritoneal cavity. A single-incision laparoscopic procedure was performed to
      locate and remove the disconnected shunt tubing, and the new shunt catheter was
      inserted through the laparoscopic port site. Laparoscopy is being used more
      frequently for evaluation and repair of distal VP shunt malfunctions, but
      generally still requires multiple incisions for port placement and insertion of
      the new shunt catheter. The single-incision technique used here is technically
      feasible, allows excellent visualization of the peritoneal cavity and does not
      require any incisions beyond the previous one used for initial shunt insertion.

PMID- 12006752
TI  - Lumboperitoneal shunting as a treatment for slit ventricle syndrome.
AB  - OBJECTIVE: Slit ventricle syndrome (SVS) has been described in hydrocephalus
      patients who continue to have shunt malfunction-like symptoms in the presence of
      a functioning shunt system and small ventricles on imaging studies. These
      symptoms usually present years after shunt placement or revision and can consist
      of headache, nausea and vomiting, lethargy and decreased cognitive skills.
      Treatments offered range from observation, medical therapy (migraine treatment)
      and shunt revision to subtemporal decompression or cranial vault expansion. We
      describe a subset of patients with SVS who were symptomatic with high
      intracranial pressure (ICP) as measured by sedated lumbar puncture and whose
      symptoms completely resolved after lumboperitoneal shunt (LPS) placement.
      METHODS: Seven patients with a diagnosis of SVS underwent lumboperitoneal
      shunting. The age at shunting ranged from 3 to 18 years. Most had undergone
      recent ventriculoperitoneal shunt (VPS) revisions for presentation of shunt
      malfunction-like symptoms. Despite this, all remained symptomatic and underwent a
      sedated lumbar puncture to measure opening pressure (OP). All had high OP in
      spite of a functional VPS and underwent LPS placement. RESULTS: All 7 patients
      had a prolonged period of overdrainage symptoms after lumboperitoneal shunting
      that resolved completely over several weeks. The initial etiology of
      hydrocephalus was reported to include trauma, aqueductal stenosis and
      intraventricular hemorrhage of prematurity. Two patients required revision of
      their LPS, after which their symptoms again resolved. CONCLUSION: In a certain
      subset of patients with SVS who are symptomatic from increased ICP, placement of
      an LPS is an effective treatment option. It appears that this subgroup of
      patients previously treated with ventriculoperitoneal shunting behave in a
      fashion similar to pseudotumor cerebri patients and respond well to
      lumboperitoneal shunting.

PMID- 12006753
TI  - Endoscopic intraventricular surgery for treatment of hydrocephalus and loculated
      CSF space in children less than one year of age.
AB  - Controversy exists regarding whether children under 1 year of age have a higher
      risk of treatment failure after neuroendoscopic procedures for the treatment of
      hydrocephalus than older children. We retrospectively reviewed the surgical
      management and clinical outcome of 15 infants who underwent neuroendoscopic
      surgery for the treatment of CSF space loculation and hydrocephalus. We performed
      8 third ventriculostomies, 3 endoscopic arachnoid cyst fenestrations, 2
      aqueductoplasties, 1 septostomy and in 1 patient, three endoscopic fenestrations
      for isolated ventricular compartments. Two of the third ventriculostomies, 1 of
      the aqueductoplasties and the 1 septostomy failed, and these patients underwent
      placement of a ventriculoperitoneal shunt. In all other patients, symptoms and
      signs related to hydrocephalus or CSF space loculation were relieved effectively
      after the endoscopic procedure. We conclude that neuroendoscopy presents an
      effective alternative for the treatment of hydrocephalus and CSF loculation in
      infants less than 1 year of age.

PMID- 12006754
TI  - Cervical subluxation after surgery and irradiation of childhood ependymoma.
AB  - Aggressive resection followed by postoperative radiation therapy directed at the
      tumor bed characterizes the treatment of childhood infratentorial ependymoma.
      Tumor resection often requires access to the upper portion of the cervical spinal
      canal, which places the patient at risk of complications, including
      destabilization. Two cases of cervical subluxation after surgery and irradiation
      for infratentorial ependymoma are presented and discussed to identify factors
      that may be responsible for this uncommon treatment complication. Cervical
      laminotomies, multiple surgeries, postoperative infection and the addition of
      radiation therapy may be contributory. Because second resection will be an
      important component of the next generation of cooperative group studies for
      infratentorial tumors, the incidence and severity of this treatment-related
      complication should be documented and efforts should be made to image the upper
      portion of the cervical spine during routine follow-up.

PMID- 12006755
TI  - Management of pediatric congenital atlantoaxial dislocation: a report of 23 cases
      from northern India.
AB  - From July 1996 to August 2001, we operated on 23 children (age 4-12 years) with
      congenital atlantoaxial dislocation (AAD). Sixteen had reducible AAD and 6 had
      the fixed type, while a single patient had basilar invagination. Preoperatively,
      these children were divided into four functional grades depending on the level of
      neurological deficits and dependence on others for activities of daily living (Di
      Lorenzo grades I-IV). There were only 2 patients with no deficits (grade I),
      while 15 of the 23 children presented with severe neurological deficits and were
      completely dependent for all activities of daily living (grade IV). Stigmata
      suggestive of congenital AAD were documented in 6 children and radiological
      osseous anomalies in 18 children. Transoral decompression and posterior
      stabilization was performed in 7 children, while 16 patients underwent the
      posterior stabilization procedure only. All patients were immobilized with a hard
      cervical collar postoperatively. Six children developed one or other treatable
      complications, of whom reoperation was indicated in 3, but could only be
      undertaken in 2 children. Retightening of the wire was done in 1 and further
      decompression of the odontoid process was carried out in the other. There was no
      postoperative deterioration in patients with no preoperative deficits (grade I).
      Ten out of the 15 children who were completely dependent for all activities in
      the preoperative period (grade IV) improved, and 6 children achieved normalcy or
      near normalcy (grade I or II). Three children deteriorated in the postoperative
      period, of whom 2 subsequently improved at follow-up. There were 2 deaths in the
      series; both these patients belonged to the severely compromised group (grade IV)
      and in addition had respiratory compromise. Bony fusion at the posterior
      stabilization site could be seen in 14 out of 16 patients screened. The various
      problems faced by the authors in managing these very fragile and severely
      compromised children with cervicomedullary compression due to congenital
      atlantoaxial dislocation in a setting with limited resources are discussed.

PMID- 12006756
TI  - Horizontal sacrum as an indicator of a tethered spinal cord.
AB  - The horizontal sacrum has never been described as an indicator of a tethered
      spinal cord following myelomeningocele closure. We retrospectively analyzed 30
      children with a myelomeningocele for this progressive change and its correlation
      with symptoms. At least two lateral radiographs over time were examined and the
      lumbosacral angle (LSA) was measured. We found that the majority of these
      children had an LSA that was greater than would be expected in patients with late
      and decreased ambulatory abilities. Also, we observed that the LSA was often
      inappropriately increased at the time many of these patients presented with
      symptoms indicative of a tethered spinal cord. We hypothesize that the LSA in
      this group of children is altered by a tethered spinal cord and that the
      horizontal nature of the sacrum may predate the clinically appreciable symptoms
      of a tethered spinal cord.

PMID- 12006757
TI  - Intracranial infantile myofibromatosis with intraparenchymal involvement.
AB  - Infantile myofibromatosis is the most common fibrous disorder of infancy and
      early childhood. Intracranial involvement is rare, with the majority of lesions
      being localized to the skull or dura with variable intracranial extension. We
      present the case of a 19-month-old girl with infantile myofibromatosis and an
      incidentally discovered, enlarging, calcified, posterior fossa mass. The patient
      underwent suboccipital craniotomy and resection of the lesion. This is the first
      report of the surgical removal of an intraparenchymal infantile myofibroma.

PMID- 12006758
TI  - Nasal dermal sinus with a dermoid cyst.

PMID- 12006759
TI  - FLAIR magnetic resonance image of a pediatric spinal epidermoid cyst.

PMID- 12006760
TI  - Selective posterior rhizotomy and intrathecal baclofen for the treatment of
      spasticity.

PMID- 12006761
TI  - High-dose chemotherapy in high-risk primary breast cancer.
AB  - The role of high-dose chemotherapy (HDCT) in high-risk primary breast cancer
      remains controversial. Although results of 8 randomized trials on HDCT in high
      risk early-stage breast cancer have become available, the data are still
      inconclusive. Only one trial revealed a significant benefit in recurrence-free
      survival for patients treated with HDCT and neither of the 8 trials showed a
      significant improvement in overall survival. However, interpretation of the data
      is limited due to a lack of statistical power in some of the trials, a relatively
      short follow-up, a relatively intensive chemotherapy regimen in the control arm
      and an inappropriate selection of cytotoxic agents with only moderate activity
      and/or unacceptable toxicity. The results of ongoing studies are therefore
      urgently needed to determine the role of HDCT in the management of primary breast
      cancer. With respect to the substantial morbidity and treatment-related
      mortality, HDCT should not be considered standard for the treatment of breast
      cancer outside clinical trials, unless a clear advantage in overall can be
      demonstrated compared to conventional chemotherapy.

PMID- 12006762
TI  - Value of neck dissection in patients with cancer of the parotid gland and a
      clinical NO neck.
AB  - Cervical lymph node metastases in patients with parotid gland carcinoma are not
      rare. Regional metastases have a significant influence on the prognosis of these
      patients. In spite of the clinical relevance of lymphogenous metastases, the
      indications for elective treatment of the neck are not well defined. In the
      present review the controversies and therapeutical strategies of ipsilateral neck
      lymph nodes and their extension in patients with potential occult lymph node
      metastases are discussed. On the basis of the published data, in consideration of
      the direction of lymphogenous metastatic spread of parotid gland carcinomas, an
      elective neck dissection is recommended in carcinomas with high percentage of
      lymphatic spread also in the N0 neck. Consideration of additional parameters (>
      T2, lymphangiosis carcinomatosa) is appropriate to perform also a neck dissection
      in carcinomas with low risk for lymphogenous metastases. An elective neck
      dissection should include levels I, II, III and upper V.

PMID- 12006763
TI  - HLA-G in melanoma: A new strategy to escape from immunosurveillance?
AB  - The non-classical HLA class-I molecule HLA-G, primarily expressed on fetal cells
      of the human placenta, has been shown to play a crucial role in maintaining an
      immuno-privileged environment at the materno-fetal interface. Fetal trophoblast
      cells are protected from attack by CD8+ cytotoxic T lymphocytes due to their
      lacking expression of classical HLA class-I molecules, again rendering them
      susceptible to natural killer (NK) cell lysis. HLA-G has been shown to interact
      with killing inhibitory receptors, hereby rescuing the fetal placenta cells from
      NK cell attack. Likewise, classical HLA class-I molecules are known to be
      frequently downregulated or lost during the development of malignancies. This
      abnormality is often associated with a poor clinical course of disease, despite
      of the frequent detection of tumor-infiltrating NK cells. This controversy seemed
      to be resolved with the detection of HLA-G expression on cells of malignant
      melanoma and other solid tumors. Since interferon(IFN)s are known for their
      ability of upregulation or induction of HLA-G expression, the potential function
      of HLA-G as a new strategy of cancer cells to escape from immunosurveillance
      might be of particular importance in malignant melanoma. The frequent use of IFN
      alpha in the immunotherapy of this malignancy might possibly worsen the already
      impaired antitumoral immune response state of melanoma patients. However, several
      studies recently failed to detect any HLA-G protein expression in cancer cell
      lines and tissues of different origin, particularly in malignant melanoma, yet
      rendering the expression and function of HLA-G in malignancies as a possibly
      overrated matter of controversial debate.

PMID- 12006764
TI  - p53, apoptosis and radiosensitivity--experimental and clinical data.
AB  - The tumor suppressor gene p53 is the most frequently mutated gene found in human
      tumors. The p53 protein is a central regulator of the cell cycle and of the
      induction of apoptosis after genotoxic stress, e.g. due to radiation or drugs.
      p53 functions mainly through transcriptional control triggered by DNA damage and
      influences multiple response pathways. Because of this important role in the
      response of cells to radiation, the interrelation between p53 status and
      radiosensitivity has found wide interest. Experimental and clinical data are
      discussed to explain the mechanism by which p53 influences the cellular response
      to radiation and to demonstrate the clinical relevance.

PMID- 12006765
TI  - Long-term follow-up of patients in four prospective studies of the German Breast
      Cancer Study Group (GBSG): A summary of key results.
AB  - Evaluation of treatment modalities and prognostic factors in early breast cancer
      requires a long-term follow-up of patients in prospective studies. The German
      Breast Cancer Study Group (GBSG) started four nationwide studies in 1983 in which
      a total of 2,746 patients have been enrolled and followed for about 10 years.
      Questions that have been addressed in these studies are still relevant today and
      comprise the role of breast-conserving therapy, the duration of adjuvant
      chemotherapy, and whether adjuvant radiotherapy is needed. The key results of
      these studies are highlighted including some important findings on prognosis,
      e.g., the role of isolated locoregional recurrence and the prognosis of patients
      with 10 or more positive lymph nodes. The data of all randomized patients were
      regularly included into the overviews of the Early Breast Cancer Trialists'
      Collaborative Group; the data of the nonrandomized patients have been used to
      examine the external validity of treatment comparisons. Overall, it can be
      concluded that the GBSG studies have made valuable and internationally recognized
      contributions to the prognosis and treatment of patients with early breast
      cancer.

PMID- 12006766
TI  - Feasibility and toxicity of weekly Paclitaxel-Carboplatin in 131 patients with
      pretreated and non-pretreated solid tumors.
AB  - BACKGROUND: Chemotherapy with paclitaxel and carboplatin 3-weekly is active in
      many tumors. Major toxicities are myelosuppression and neurotoxicity. Weekly
      administration of taxanes allows high dose intensity with reduced toxicity.
      PATIENTS AND METHODS: 131 patients with solid tumors were treated as outpatients
      with paclitaxel 75 mg/m(2) and carboplatin AUC 2-3 days 1, 8, 15 every 4 weeks
      irrespective of pretreatment and partly in neoadjuvant and multimodal concepts.
      RESULTS: 125 patients (median age 58 years) were evaluable for response and
      toxicity, of whom 45 suffered esophageal carcinoma (19 patients in neoadjuvant
      treatment) and 31 non-small cell lung cancer. 49 patients were pretreated. 23
      patients received concomitant radiotherapy of esophagus or lung in doses ranging
      from 40 to 60 Gy. We observed a low hematologic toxicity with 15.2% grade-III/IV
      leukopenia/granulocytopenia and 3.2% thrombocytopenia grade III/IV. Neurotoxicity
      grade II was reported in 14 patients. Main toxicity with radiotherapy was
      esophagitis grade II or III in 7 out of 23 patients. Overall response rate was
      54.2%. 5 out of 19 patients treated neoadjuvantly for esophageal cancer reached a
      pathological complete response. CONCLUSIONS: Weekly paclitaxel and carboplatin is
      safe and feasible in outpatients and a high dose intensity can be achieved. The
      favorable toxicity profile allows treatment of elderly and pretreated patients.
      Response rate is high including pathological complete responses and responses
      appear quickly, making this therapy most suitable for multimodal and neoadjuvant
      treatments.

PMID- 12006767
TI  - A new chemoembolization protocol in refractory liver metastasis of colorectal
      cancer--a feasibility study.
AB  - INTRODUCTION: In patients with advanced colorectal cancer (CRC) refractory to
      systemic chemotherapy including 5-fluorouracil (5-FU) / folinic acid (FA),
      oxaliplatin and irinotecan we assessed the feasibility, toxicity and response to
      hepatic transcatheter arterial chemoembolization (TACE). At the time of
      treatment, patients had exclusively or dominantly liver metastasis of CRC.
      PATIENTS AND METHODS: The following protocol was applied via a selective
      transfemoral hepatic arterial approach: mitomycin C 5 mg/m(2), interferon-alpha2b
      4.5 Mio IU, dexamethasone 20 mg mixed with Amilomer DSM 45/25 (Spherex((R))) days
      1 and 2 i.a. (bolus), oxaliplatin 50 mg/m(2) (2 h) day 1 i.a., FA 500 mg/m(2) (2
      h) day 1 i.v., and 5-FU 1.500 mg/m(2) (24 h) day 1 i.a. Cycles have been repeated
      at days 15-22. The dose was adjusted according to the pretreatment performance
      status and elevation of alkaline phosphatase, bilirubin and serum albumin.
      Treatment was continued until progression or emergence of intolerable toxicity.
      RESULTS: 11 patients received a total number of 43 TACE, with a range of 2-6 per
      patient. There was no TACE-related mortality. 4 patients died 5, 8, 10 and 11
      months after initiation of treatment due to progression of disease. 7 patients
      are alive at 4+ (n = 2), 5+ (n = 1), 6+ (n = 1), 7+ (n = 1) and 11+ (n = 2)
      months after start of treatment. Toxicity (CTC) was mild with grade I-II asthenia
      (n = 10), grade I-II neurotoxicity (n = 5), grade II nausea and/or vomiting (n =
      2) and grade II diarrhea (n = 1). Treatment had to be postponed due to grade I
      thrombocytopenia in 2 patients. No bleeding episodes or obvious infectious
      complications occurred during treatment intervals. 1 patient experienced an
      allergic reaction to oxaliplatin which led to exclusion from further therapy.
      Arterial catheter dislocation occurred in 3 patients. In 10 patients evaluable
      for response we observed 3 partial responses, 2 minor responses, and 4 times
      stable disease. Only 1 patient had further progression of disease under
      treatment. CONCLUSION: TACE, using a combination of mitomycin C, dexamethasone
      and interferon-alpha2b mixed with Spherex((R)), followed by oxaliplatin, FA and 5
      FU, appears to be an effective and feasible treatment option in the case of liver
      metastasis of CRC refractory to standard systemic chemotherapy. This treatment is
      associated with tolerable toxicity, which becomes apparent mainly as asthenia,
      neurotoxicity or thrombocytopenia. These preliminary data warrant further
      evaluation for patients with refractory disease and would probably also be of
      interest for first-line treatment in this patient population.

PMID- 12006768
TI  - Socio-demographic and medical characteristics of advanced cancer patients using
      conventional or complementary medicine.
AB  - BACKGROUND: To provide prospective comparative data describing the profiles of
      two patient populations attending conventional or complementary medicine
      institutions. PATIENTS AND METHODS: A registration study was set up in an
      oncology ward at the Institute for Medical Oncology (IMO) of the University
      Hospital in Bern, and at the Lukas Clinic (LC) for Anthroposophical Cancer
      Treatment in Arlesheim, Switzerland. The same eligibility criteria were applied
      to enrol into the study all newly referred or newly diagnosed patients with
      advanced cancer over a 2-year period. Their socio- demographic and clinical
      characteristics at presentation have been compared between the two institutions.
      RESULTS: Patients at LC are primarily females, of higher educational level, and
      living in an urban environment. Patients at LC are also more frequently of poorer
      performance status but present with less comorbidity and a longer interval
      between diagnosis of metastatic disease and accrual into the study. CONCLUSION:
      This study suggests that the respective merits of these two schools of medicine
      can be assessed successfully only through a concrete research partnership based
      on rigorously controlled clinical trials.

PMID- 12006769
TI  - Tumor cell motility as a novel target in cancer--experimental and clinical
      results.
AB  - BACKGROUND: Surgery, chemotherapy and radiotherapy are the mainstay of tumor
      management. However, in systemic disease cure can be achieved in yet a few tumor
      entities. Based on cell biological research we have characterized the process of
      tumor progression and metastasis and disclosed that the loss of cell-cell
      adhesion in association with an increased tumor cell motility is an essential
      feature of the malignant potential of a tumor. METHODS: According to this
      principle we derived therapeutical methods differing from hitherto existing
      treatments by being exclusively focused on tumor cell motility. Characterization
      of so-called anti-motility factors was performed biochemically as well as with
      motility assays by in vitro studies in established bladder carcinoma cell lines.
      RESULTS: We evaluated the potential therapeutic benefit in a model of chemically
      induced bladder carcinoma followed by a phase I/II trial applying antimotility
      factors in patients with advanced bladder cancer. CONCLUSION: Both basic research
      as well as the results of first clinical trials confirm, that advanced carcinomas
      can be influenced by inhibition of tumor cell motility.

PMID- 12006770
TI  - Multiple application of drugs in rats--a new port system.
AB  - The implantation of a small port system for repeated intravenous applications of
      drugs in rats is described. The system basically consists of a Teflon catheter
      which is inserted into the right internal jugular vein. The open end of the
      catheter under the right foreleg is subcutaneously carried through to the back
      and closed by a small port. The port then is implanted into a skin pocket on the
      back of the rat. The advantage of this method is that repeated intravenous
      injections of drugs into rats can easily be applied with high accuracy.
      Complications were rarely observed (7%) and could be mastered successfully in all
      cases.

PMID- 12006771
TI  - Capecitabine as second-line treatment for metastatic cholangiocarcinoma: a report
      of two cases.
AB  - BACKGROUND: The management of recurrent, metastatic cholangiocarcinoma still
      remains a problem since this tumor entity is classified as chemotherapy
      resistant. When advanced or metastatic disease is diagnosed, the therapeutic
      efforts are essentially directed toward palliation. PATIENTS AND METHODS: We
      report on 2 patients suffering from metastatic cholangiocarcinoma. Both had
      received previous chemotherapy for metastatic disease, including hepatic artery
      infusion [5-fluorouracil (5-FU) / folinic acid (FA) and oxaliplatin] and a
      combination therapy consisting of 5-FU/FA and gemcitabine. Since a progression of
      the disease was diagnosed, both patients were started on oral capecitabine at a
      daily dose of 2,500 mg/m(2) in 2 divided doses for 2 weeks, followed by 1 week
      rest. RESULTS: Capecitabine was tolerated well and severe side effects were not
      observed. A stop of progression, documented by imaging procedures and tumor
      marker kinetics, was achieved in both patients. CONCLUSION: Capecitabine could
      potentially be used for secondline treatment in patients with progressive
      metastatic cholangiocarcinoma.

PMID- 12006772
TI  - Fish consumption and stroke: benefit or risk?

PMID- 12006773
TI  - Fish consumption and stroke: a community case-control study in Asturias, Spain.
AB  - BACKGROUND: The relationship between fish consumption and stroke is
      controversial. Actually, a low fish consumption may protect against ischemic
      stroke, while a fish diet is ecologically associated with an increased risk of
      hemorrhagic stroke. OBJECTIVE: This study seeks to examine the relationship
      between fish consumption and stroke in a population with a high fish consumption
      and stroke incidence. METHODS: A population-based case-control study was
      performed, lasting from September 1990 to December 1991. The study comprised 440
      incident cases of stroke and 473 controls between the ages of 40 and 85. Cases
      were defined following WHO criteria, and controls were randomly selected from the
      study base population. Information on fish consumption was obtained with a food
      frequency questionnaire. RESULTS: After controlling for age, energy intake and
      several stroke risk factors, the risk of stroke increased with the consumption of
      fish, chi(2) 4.12, p = 0.04. Those in the highest quintile of consumption (46 g
      of fish/day) had a multivariate adjusted odds ratio (OR) of 1.95 (95% CI: 1.14
      3.33) as compared to those in the lowest quintile of fish consumption (11 g/
      day). The risk of cerebral infarction also increased with the consumption of
      fish, showing an OR of 1.98 (95% CI: 1.08-3.47). Those in the highest quintile of
      n-3 fatty acid consumption (660 mg/day) were at borderline higher risk of stroke,
      with an OR of 1.76 (95% CI: 0.95-3.26), and also of cerebral infarction (OR:
      1.89, 95% CI: 0.95-3.75), as compared to those in the lower quintile of n-3 fatty
      acids consumption (115 mg/day). CONCLUSION: Although misclassification of
      exposure and residual confounding by unmeasured factors cannot be ruled out, a
      high fish consumption was associated with an increased risk of stroke and
      cerebral infarction in this study. More studies should be done to clarify the
      effect of fish consumption on stroke and stroke subtype in order to issue
      recommendations regarding the consumption of fish and the risk of stroke.

PMID- 12006774
TI  - Alcohol drinking and risk of hemorrhagic stroke.
AB  - In view of conflicting prior reports, we prospectively studied associations
      between alcohol consumption and subsequent hospitalization for hemorrhagic stroke
      (HS) in 431 persons. Alcohol use was determined at examinations in 1978-1984
      among 128,934 members of a prepaid health plan. Cox proportional hazards models,
      with 6 covariates, yielded the following multivariate relative risks (95% CI's)
      for HS: lifelong abstainers (ref) = 1.0, exdrinkers = 0.9 (0.5-1.5), persons
      drinking <1/month = 1.1 (0.8-1.4), >1/month; <1 drink/day = 0.7 (0.5-0.9), 1
      2/day = 0.8 (0.6-1.1), 3-5/day = 1.0 (0.6-1.5), 6+/day = 1.9 (1.0-3.5).
      Relationships to alcohol were similar for subarachnoid (31% of HS) or
      intracerebral hemorrhage (69% of HS) and in men or women. Beverage choice (wine,
      beer, and liquor) was not independently related. We conclude that only heavy
      drinking is weakly related to increased HS risk and that light drinking need not
      be proscribed with respect to HS risk.

PMID- 12006775
TI  - Association between blood pressure and cognitive function in a biracial community
      population of older persons.
AB  - We examined whether or not blood pressure is related to cognitive function in a
      cross-sectional study of a biracial community of 5,816 persons aged 65 years and
      older. Blood pressure had a curvilinear association with cognitive performance in
      linear regression models adjusted for age, sex, race and education. Scores were
      lower by 2-5 percentiles at 100 mm Hg systolic pressure compared to scores at the
      mean of 140 mm Hg and lower by <1 percentile at 180 mm Hg. For diastolic
      pressure, scores were lower by 2-3 percentiles at 60 mm Hg and by 1-2 percentiles
      at 100 mm Hg compared to scores at the mean (77 mm Hg). The differences in the
      scores with low blood pressure were reduced with further adjustment for body mass
      index, self-perceived health status, depressive symptoms, alcohol use and
      smoking. The curvilinear associations were stronger among persons with histories
      of stroke, myocardial infarction and hypertension. The cross-sectional
      association between blood pressure and cognitive functions is small and
      curvilinear and more apparent in persons with cardiovascular conditions.

PMID- 12006776
TI  - Trends in hospitalized stroke for blacks and whites in the United States, 1980
      1999.
AB  - BACKGROUND: Racial differences in stroke mortality are widely recognized, but it
      is unclear whether or not these differences are due mainly to blacks having a
      greater stroke incidence or higher case fatality rates compared to those of
      whites. OBJECTIVES: The aim of this study was to describe the race-specific US
      trends in hospital discharge rates and in-hospital mortality among stroke
      patients for the period 1980-1999. It was hypothesized that the hospital
      discharge rates and in-hospital mortality among stroke patients would be greater
      for blacks than for whites. METHODS: Data from the National Hospital Discharge
      Survey for the period 1980-1999 were used to identify stroke subjects according
      to the codes of the International Classification of Diseases, ninth revision
      (codes 430-434 and 436). Direct standardization and Poisson regression were used
      to compare hospitalized stroke morbidity and mortality rates between blacks and
      whites. The main outcome measures were the number of stroke discharges and in
      hospital deaths for black and white stroke patients. RESULTS: Between the years
      1980 and 1999, the hospital discharge rates for stroke increased for blacks (n =
      8,700) and decreased for whites (n = 46,154); the in-hospital mortality rates
      decreased for both black and white stroke patients. Generally, the risk of a
      stroke hospitalization was greater for blacks than for whites by more than 70%,
      whereas both groups were similar in terms of in-hospital mortality rates among
      stroke patients. CONCLUSIONS: Differences between blacks and whites in terms of
      stroke mortality are more likely due to differences in stroke incidence rather
      than case fatality. These data imply that greater attention should be given to
      primary/secondary prevention and that additional research is needed to understand
      the reasons for these patterns.

PMID- 12006777
TI  - Stroke mortality in Andalusia (Spain) from 1975 to 1999: effect of age, birth
      cohort and period of death.
AB  - The aim of this study was to analyze stroke mortality rates in Andalusia during
      the period from 1975 to 1999 by studying age, cohort and period effects. Deaths
      due to stroke along with the corresponding population figures were divided into
      11 age groups and five 5-year periods. From this, age-specific mortality rates
      for 15 birth cohorts were then computed. These were plotted and fitted to Poisson
      regression models to assess age, period and cohort effects. An exponential age
      effect was present for both sexes regardless of cohort or period. The rates of
      stroke mortality decreased significantly among both sexes in Andalusia during the
      study period, although in recent years, this declining trend has started to slow
      down, primarily in males. Age- and period-adjusted stroke mortality was greater
      for earlier cohorts and lower for generations born at the beginning of the 20th
      century.

PMID- 12006778
TI  - Accuracy of death certificates for motor neuron disease and multiple sclerosis in
      the province of Palermo in southern Italy.
AB  - Mortality studies based on death certificates (DCs) are relatively inexpensive
      and easy to conduct. Therefore, they are frequently used to evaluate variations
      of geographical and temporal patterns, particularly in uncommon diseases. Recent
      surveys of motor neuron disease (MND) and multiple sclerosis (MS) based on
      official mortality statistics in Italy showed a decreasing trend of mortality
      from northern to southern Italy. To evaluate if DCs are homogeneously recorded in
      Italy and whether or not they can be considered a good instrument for mortality
      studies, we assessed the accuracy of DCs for MND and MS in the province of
      Palermo, Italy, and compared our results with those reported in other studies. We
      searched the archives of the neurological clinic of the University of Palermo for
      patients affected by one of the two diseases who were residents and were
      diagnosed in Palermo province. We found 157 patients with definite MND and 360
      with clinically definite MS. Seventy-eight out of the 157 MND patients and 43 out
      of the 360 MS patients had died. Considering the underlying cause of death, the
      true-positive rate was 48% [95% confidence interval (CI) 36-60%] for MND and 46%
      (95% Cl 30-62%) for MS. The rates we found for MND were lower than those reported
      either in Italy or worldwide. This result suggests caution in formulating
      gradient hypotheses for MND. Concerning MS, the rate we found was low, but
      similar to that found by others. This indicates that a mortality survey of MS
      based on DCs is unlikely to be contributory.

PMID- 12006779
TI  - Human T cell lymphotropic virus type 1-associated myelopathy in Sao Paulo,
      Brazil. Epidemiologic and clinical features of a university hospital cohort.
AB  - We report epidemiologic and clinical features of human T cell lymphotropic virus
      type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis in a Brazilian
      cohort of 86 patients from a university hospital. Cerebrospinal fluid (CSF)
      abnormalities and magnetic resonance imaging (MRI) findings were correlated with
      neurologic signs and symptoms. The patients' mean age at disease onset was 43.2
      years and the female to male ratio 1.5:1. Risk factors for retroviral exposure
      included blood transfusions, sexual transmission and intravenous drug use.
      Neurologic manifestations consisted mostly of spastic paraparesis, of gradual and
      asymmetric onset, with increased deep-tendon reflexes. Disability was associated
      with disease duration. CSF findings included mild mononuclear pleocytosis and
      elevated protein levels. MRI showed hemispheric areas of high signal intensity in
      32.7% and spinal cord atrophy in 5.6% of cases, particularly in patients with
      longer duration of disease. A high frequency of past blood transfusion (32.6%)
      suggests that blood-borne infection was an important means of HTLV infection
      before implementation of screening of blood donors in Brazil.

PMID- 12006780
TI  - Progesterone induces dephosphorylation and inactivation of tyrosine hydroxylase
      in rat hypothalamic dopaminergic neurons.
AB  - After in vivo treatment, progesterone initially decreases tyrosine hydroxylase
      (TH) activity in the TIDA neurons, but subsequently increases TH activity with
      prolonged treatment. In order to explore the cellular mechanism for
      progesterone's effect, this study examined the acute inhibitory action of
      progesterone on TH activity in rat fetal hypothalamic dopaminergic neurons in
      vitro. Progesterone caused a rapid decrease in TH activity within 1 h, which was
      sustained for at least 6 h. However, the dopaminergic cells became refractory to
      progesterone with continuous treatment for 12 h to 10 days. Progesterone (10-100
      nM) treatment suppressed TH activity in a concentration-dependent manner. The
      inhibitory effect of progesterone was dependent on prior exposure to estradiol.
      Whereas progesterone decreased TH activity, A ring-reduced metabolites of
      progesterone did not alter TH activity, suggesting that the response was specific
      to progesterone. Progesterone decreased radiolabeled phosphate incorporation into
      TH protein. Okadaic acid, a phosphoprotein phosphatase inhibitor, prevented the
      progesterone-induced suppression of TH activity and phosphate incorporation into
      TH, implicating dephosphorylation of TH as the cellular mechanism. In contrast,
      neither TH mRNA levels nor TH protein content was altered after 1 or 12 h of
      progesterone treatment. Progesterone decreased TH activity after pretreatment of
      the hypothalamic cells for 2 or 24 h with actinomycin D, an RNA synthesis
      inhibitor, suggesting that increased transcription does not mediate the effect.
      These data indicate that the acute progesterone-induced decline in TH activity is
      caused by dephosphorylation of TH.

PMID- 12006781
TI  - Ovarian hormones do not attenuate methamphetamine-induced dopaminergic
      neurotoxicity in mice gonadectomized at 4 weeks postpartum.
AB  - The present study was undertaken to assess the ability of ovarian hormones to
      alter methamphetamine (MA)-induced dopaminergic toxicity in male and female mice
      gonadectomized at 4 and 6 weeks of age. None of the following three treatments,
      estradiol benzoate (EB, 3 x 0.47 microg), progesterone (Prog, 3 x 0.47 microg),
      or EB (2 x 0.47 microg) followed by Prog (0.47 microg), affected the dopamine
      (DA)-depleting effects of MA in male and female mice gonadectomized when they
      were 4 weeks old. However, in contrast to the findings that male mice are more
      sensitive to MA-induced DA depletion than female mice, no sexual differences in
      the sensitivity to MA treatment were observed in mice gonadectomized at this age.
      Moreover, three daily doses of EB (0.47 microg) and EB (0.47 microg) combined
      with 4-hydroxytamoxifen (4OHT, 6 microg) effectively attenuated striatal DA
      depletion produced by MA in female mice ovariectomized at 6 weeks of age. Three
      daily doses of Prog (0.47 microg) and EB (0.47 microg) combined with 4OHT (6
      microg) significantly attenuated MA-induced striatal DA depletion in male mice
      gonadectomized at 6 weeks of age. Taken together, the modulating effects of
      ovarian hormones on MA-induced DA depletion in mouse striatum could be sex- and
      age-dependent. 4OHT did not block the protecting effects of EB on MA-induced DA
      depletion in female and male mice, suggesting that the estrogen receptor may not
      be involved in the protective effects of EB on attenuating MA-induced DA
      toxicity.

PMID- 12006782
TI  - A neuroactive steroid, pregnenolone, alters the striatal dopaminergic tone before
      and after puberty.
AB  - Neuroactive steroids are known to modulate excitability in neurons. Neuronal
      activity during early development is critical to normal development of the brain.
      A neuroactive steroid, pregnenolone, was administered (10 microg/g) to rats from
      postnatal day 3 (PD 3) through PD 7. Dopamine (DA), serotonin (5-HT) and their
      metabolites were measured in the striatum. The results showed that neonatal
      treatment with pregnenolone increases DA and 5-HT turnover in the striatum at 3
      weeks of age. The increased 5-HT turnover in the pregnenolone-treated animals was
      normalized at 14 weeks of age whereas the DA turnover in the pregnenolone-treated
      group was lower than in the control group. The present study indicated that
      pregnenolone treatment during the neonatal period induced abnormal development of
      the striatal dopaminergic function in adulthood.

PMID- 12006783
TI  - Sex hormone receptors are present in the human suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) is the clock of the brain that orchestrates
      circadian and circannual biological rhythms, such as the rhythms of hormones,
      body temperature, sleep and mood. These rhythms are frequently disturbed in
      menopause and even more so in dementia and can be restored in postmenopausal
      women by sex hormone replacement therapy (SHRT). Although it seems clear, both
      from clinical and experimental studies, that sex hormones influence circadian
      rhythms, it is not known whether this is by a direct or an indirect effect on the
      SCN. Therefore, using immunocytochemistry in the present study, we investigated
      whether the human SCN expresses sex hormone receptors in 5 premenopausal women
      and 5 young men. SCN neurons appeared to contain estrogen receptor-alpha
      (ERalpha), estrogen receptor-beta (ERbeta) and progesterone receptors. Median
      ratings of ER immunoreactivity per individual and per gender group revealed a
      statistically significantly stronger nuclear ERalpha expression pattern in female
      SCN neurons (p < 0.05). No significant sexual dimorphic tendency was observed for
      nuclear ERbeta (p > 0.1) and progesterone receptors (p > 0.7). These data seem to
      support previously reported functional and structural SCN differences in relation
      to sex and sexual orientation and indicate for the first time that estrogen and
      progesterone may act directly on neurons of the human biological clock. In
      addition, the present findings provide a potential neuroendocrine mechanism by
      which SHRT can act to improve or restore SCN-related rhythm disturbances, such as
      body temperature, sleep and mood.

PMID- 12006784
TI  - Vaginocervical stimulation releases oxytocin within the spinal cord in rats.
AB  - Vaginocervical stimulation (VS) significantly elevated the concentration of
      oxytocin (OT) in spinal cord superfusates of 8 intact urethane-anesthetized rats
      measured 10-15 min after VS (median [interquartile range]: 1.7 [1.00-3.37] pg/ml)
      compared to that measured 10-15 min before VS (1.1 [1.01-1.40] pg/ml). When VS
      was administered once (n = 8), it produced a 55% increase over baseline values;
      when administered a second time 45 min later (n = 6), it produced only a 22%
      increase over pre-VS values. The effects of estrogen on the VS-induced release of
      OT were then investigated using ovariectomized rats that were treated either with
      estradiol benzoate (EB; 10 microg/100 g bw) (n = 6) or with an oil vehicle (n =
      6) subcutaneously for 3 days. The EB treatment significantly elevated the basal
      levels of OT released into spinal cord superfusates above vehicle control levels.
      Within 5-10 min after the onset of VS, OT concentrations in the superfusates were
      significantly higher in EB-treated than in vehicle-treated rats. The vehicle
      treated rats did not show a significant elevation in OT concentration following
      VS. To rule out the possibility that the posterior pituitary gland was the source
      of this OT, the effect of hypophysectomy (HYPOX) was assessed on the VS-induced
      release of OT into spinal cord superfusates and plasma. The concentration of OT
      in spinal cord superfusates of both the HYPOX (n = 5) and intact rats (n = 6)
      increased significantly from 5.8 [4.4-6.5] pg/ml pre-VS to 7.9 [6.7-10.3] pg/ml
      immediately after VS, and from 4.4 [3.8-5] pg/ml pre-VS to 5.1 [4.6-5.7] pg/ml
      immediately after VS, respectively. There was no significant difference in
      baseline levels of OT in cerebrospinal fluid between the two groups. By contrast,
      plasma OT levels, while significantly elevated in response to VS from 3.42 [2.9
      5.34] pg/ml baseline to 7.25 [5.33-15.77] pg/ml in the intact group, failed to
      respond significantly to VS in the HYPOX group (n = 5). The present findings
      provide evidence of a direct estrogen-dependent release of OT within the spinal
      cord in response to VS, presumably via descending oxytocinergic neurons.

PMID- 12006785
TI  - Influence of photoinhibition on the morphology and function of pituitary
      lactotropes in male golden hamsters.
AB  - Inhibition of prolactin (PRL) secretion has been previously shown in pituitaries
      from male and female hamsters exposed to short photoperiods. The purpose of the
      present study was to analyze the possible quantitative immunohistochemical and
      ultrastructural changes of PRL cells in male golden hamsters undergoing
      regression and spontaneous recrudescence, correlating the morphological findings
      with circulating PRL levels. Thus, adult male golden hamsters were exposed for 8,
      16, 22 and 28 weeks to either short photoperiods (SP: 6 h light, 18 h darkness)
      or long photoperiods (LP: 14 h light, 10 h darkness). Pituitaries were processed
      for both light and electron microscopy, and serum levels of PRL were assessed by
      radioimmunoassay (RIA). Volume density (VD = cell area/reference area) and cell
      density (CD = number of cells/reference area) of lactotropes were measured with
      an image analysis system (Imaging Technology, Software Optimas 5.2). One hundred
      lactotropes were recorded for measuring several ultrastructural parameters. When
      analyzing the lactrotrope cell population from animals submitted to SP, the VD
      and CD were found to be significantly (p < 0.05) diminished with respect to those
      of the groups submitted to LP at weeks 8, 16 and 22. However, at week 28 a
      spontaneous recrudescence appeared. The lactotropes from animals submitted to LP
      for 8, 16, 22 and 28 weeks exhibited numerous large electrondense secretory
      granules. The rough endoplasmic reticulum (RER) presented some flat cisternae and
      numerous free ribosomes. Animals submitted to SP for 8 weeks showed a number of
      medium and large secretory granules, and the RER exhibited mainly numerous free
      ribosomes. In those animals submitted to SP for 16 and 22 weeks, lactotropes were
      found smaller and showed small and medium-sized secretory granules decreased in
      number. The Golgi complex exhibited some immature granules and dilated cisternae,
      while the RER did not present differences with respect to the 8-week SP group.
      The hamsters submitted to SP for 28 weeks presented medium and large secretory
      granules, and the RER exhibited dilated irregular cisternae. The ultrastructural
      morphometric parameters showed a decrease (p < 0.05) in the number of secretory
      granules and exocytotic profiles, as well as a diminution (p < 0.05) in the areas
      of Golgi complex, RER, secretory granules, and individual mean area of secretory
      granule during the 16 and 22 weeks of SP. Serum PRL levels were severely reduced
      under SP. This decrease was greater at 16 weeks than at 8 weeks of exposure. When
      hamsters were kept for 22 weeks under SP, PRL levels started their recovery.
      Thus, at the end of the experiment, the PRL values returned to near those of LP
      group. In summary, we found quantitative immunohistochemical and ultrastructural,
      as well as biochemical changes that suggest an inhibition of synthesis, storage
      and release of PRL in male golden hamsters submitted to SP, with a spontaneous
      recrudescence appearing at the end of the study.

PMID- 12006786
TI  - Guinea pig gonadotropin-releasing hormone: expression pattern, characterization
      and biological activity in rodents.
AB  - Gonadotropin-releasing hormone (GnRH) is a decapeptide widely known for its role
      in regulating vertebrate reproduction by serving as a signal from the
      hypothalamus to pituitary gonadotropes. The first form of GnRH to be identified
      was isolated from mammals (mGnRH) and the same form has been reported for all
      mammals studied, which includes marsupials and placental mammals. Later, another
      variant, chicken GnRH-II (cGnRH-II) was shown to be expressed together with mGnRH
      in the brains of all jawed vertebrates, including mammals such as rats, monkeys
      and humans. Our objective was to characterize a third form of GnRH that was
      isolated previously as mRNA from guinea pigs (gpGnRH), but has not been reported
      for any other mammal to date. Furthermore, the gonadotropic activity of gpGnRH
      has not been fully characterized. Our results, using chromatographical and
      immunological methods, show for the first time that gpGnRH is expressed together
      with mGnRH in some rodents (wild guinea pig and capybara), but not in others
      (mouse and hamster). Also, the gonadotropic activity of gpGnRH and mGnRH was
      tested in two different rat cell culture systems. Although there have been
      reports that the salmon(s) form of GnRH is present in mammals, we did not detect
      sGnRH in capybara, wild guinea pigs, hamsters, rats or mice. Taken together with
      previous reports, the present results support the idea that the expression of
      multiple GnRH variants in a single species is a common pattern in most vertebrate
      groups.

PMID- 12006787
TI  - Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular
      fibrillation and cardiopulmonary resuscitation.
AB  - OBJECTIVE: We recently demonstrated that vasopressin alone resulted in a poorer
      outcome in a pediatric porcine model of asphyxial cardiac arrest when compared
      with epinephrine alone or with epinephrine plus vasopressin in combination.
      Accordingly, this study was designed to differentiate whether the inferior
      effects of vasopressin in pediatrics were caused by the type of cardiac arrest.
      DESIGN: Prospective, randomized laboratory investigation that used an established
      porcine model for measurement of hemodynamic variables and organ blood flow.
      SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11
      kg. INTERVENTIONS: After 8 mins of ventricular fibrillation and 8 mins of
      cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45
      microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with
      0.8 units/kg vasopressin (n = 6) was administered. Six minutes after drug
      administration, a second respective bolus dose of 0.8 units/kg vasopressin, 200
      microg/kg epinephrine, or a combination of 200 microg/kg epinephrine with 0.8
      units/kg vasopressin was given. Defibrillation was attempted 20 mins after
      initiating cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Mean +/-
      sem left ventricular myocardial blood flow 2 mins after each respective drug
      administration was 65 +/- 4 and 70 +/- 13 mL x min(-1) x 100 g(-1) in the
      vasopressin group; 83 +/- 42 and 85 +/- 41 mL x min(-1) x 100 g(-1) in the
      epinephrine group; and 176 +/- 32 and 187 +/- 29 mL x min(-1) x 100 g(-1) in the
      epinephrine-vasopressin group (p <.006 after both doses of epinephrine
      vasopressin vs. vasopressin and after the first dose of epinephrine-vasopressin
      vs. epinephrine, respectively). At the same times, mean +/- sem total cerebral
      blood flow was 73 +/- 3 and 47 +/- 5 mL x min(-1) x 100 g(-1) after vasopressin;
      18 +/- 2 and 12 +/- 2 mL x min(-1) x 100 g(-1) after epinephrine; and 79 +/- 21
      and 41 +/- 8 mL x min(-1) x 100 g(-1) after epinephrine-vasopressin (p <.025
      after both doses of vasopressin and epinephrine-vasopressin vs. epinephrine).
      Five of six vasopressin-treated, two of six epinephrine-treated, and six of six
      epinephrine-vasopressin treated animals had return of spontaneous circulation
      (nonsignificant). CONCLUSIONS: In this pediatric porcine model of ventricular
      fibrillation, the combination of epinephrine with vasopressin during
      cardiopulmonary resuscitation resulted in significantly higher levels of left
      ventricular myocardial blood flow than either vasopressin alone or epinephrine
      alone. Both vasopressin alone and the combination of epinephrine with
      vasopressin, but not epinephrine alone, improved total cerebral blood flow during
      cardiopulmonary resuscitation. In stark contrast to asphyxial cardiac arrest,
      vasopressin alone or in combination with epinephrine appears to be of benefit
      after ventricular fibrillation in the pediatric porcine model.

PMID- 12006788
TI  - Successful determination of lower inflection point and maximal compliance in a
      population of patients with acute respiratory distress syndrome.
AB  - OBJECTIVE: To compare the ease and efficacy of two commonly used methods for
      choosing optimal positive end-expiratory pressure (PEEP) in patients with acute
      respiratory distress syndrome: a static pressure-volume curve to determine the
      lower inflection point (P(flex)) and the "best PEEP" (PEEP(best)) as determined
      by the maximal compliance curve. DESIGN: Prospective study. SETTING: Medical and
      respiratory intensive care units of university-associated tertiary care hospital.
      PATIENTS: Twenty-eight patients on mechanical ventilation with acute respiratory
      distress syndrome. INTERVENTIONS: A critical care attending physician or fellow
      and an experienced respiratory therapist attempted to obtain both static pressure
      volume curves and maximal compliance curves on 28 patients with acute respiratory
      distress syndrome by using established methods that were practical to everyday
      use. The curves then were used to determine both P(flex) and PEEP(best), and the
      results were compared. MEASUREMENT AND MAIN RESULTS: Our results showed at least
      one value for optimal PEEP was obtained in 26 of 28 patients (93%). P(flex) was
      determined in 19 (68%), a PEEP(best) in 24 (86%), and both values in 17 (61%). In
      patients who had both P(flex) and PEEP(best) determined, there was a close
      concordance (+/-3 cm H2O) in 60%. When the values of P(flex) and PEEP(best) were
      interpreted by two additional investigators, there was unanimous agreement on the
      P(flex) (+/-3) only 64% of the time. There was agreement on the value of
      PEEP(best) 93% of the time. CONCLUSIONS: Our data show that optimal PEEP, as
      determined by a pressure-volume curve and a maximal compliance curve, are
      sometimes unobtainable by practical means but, when obtained, often correspond. A
      maximal compliance is more often identified, has less interobserver variability,
      and poses less risk to the patient. We conclude that determining optimal PEEP by
      maximal static compliance may be easier to measure and more frequently obtained
      at the bedside than by using a static pressure-volume curve.

PMID- 12006789
TI  - Association between a genomic polymorphism within the CD14 locus and septic shock
      susceptibility and mortality rate.
AB  - OBJECTIVE: Genetic differences in immune responses may affect susceptibility to
      and outcome of septic shock. CD14 seems to be an important part of the innate
      immune system, initiating antimicrobial response. We evaluated the frequency of a
      recently discovered CD14 promoter gene polymorphism (C to T transition at base
      pair -159) among patients with septic shock compared with those in a control
      group. DESIGN: Multiple-center study. SETTING: Hospital research department.
      PATIENTS: Ninety consecutive white patients with septic shock were included. The
      control group consisted of 122 age- and gender-matched white subjects.
      INTERVENTIONS: In both groups, the C-159T CD14 promoter genetic polymorphism was
      determined by using polymerase chain reaction and subsequent Hae III restriction
      enzyme digestion of the polymerase chain reaction products. MEASUREMENTS AND MAIN
      RESULTS: The C-159T polymorphism and the TT genotype were significantly
      overrepresented among septic shock patients compared with controls. Within the
      septic shock group, the mortality of patients with TT genotype (71%) was
      significantly higher than in patients with other genotypes (48%; Pearson chi
      square, p =.008). In a multiple logistic regression model, the TT genotype was
      independently associated with an increased relative risk of death (odds ratio,
      5.30; 95% confidence interval, 1.20-22.50, p =.02). CONCLUSIONS: The C-159T
      polymorphism affects susceptibility to septic shock and seems to be a new genetic
      risk factor for death.

PMID- 12006790
TI  - Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate
      ribose) synthetase in a porcine model of severe bacterial sepsis.
AB  - OBJECTIVE: To determine whether activation of the nuclear enzyme poly(adenosine
      5'-diphosphate [ADP]-ribose) synthetase (PARS) contributes to mortality rate,
      myocardial dysfunction, and cardiovascular collapse in a porcine model of sepsis
      induced by implantation of an infected clot. DESIGN: Prospective, random animal
      study. SETTING: Research laboratory at Rush Presbyterian St. Luke's Medical
      Center. SUBJECTS: Twenty pigs were chronically instrumented with intracardiac
      transducers to measure left ventricular pressure, sonomicrometer crystals in the
      left ventricle to measure short axis diameter, an ultrasonic flow meter to
      measure cardiac output, and catheters in the pulmonary artery and aorta to
      measure blood pressures and collect samples. INTERVENTIONS: By using a randomized
      study design, we administered either the novel potent PARS inhibitor PJ34 (10
      mg/kg for 1 hr, 2 mg x kg(-1) x hr(-1) for 96 hrs) or vehicle to pigs immediately
      before intraperitoneal implantation of Escherichia coli 0111.B4 (2.3 +/- 0.1 x
      10(10) colony-forming units/kg)-laden fibrin clots to produce peritonitis and
      bacteremia. MEASUREMENTS AND MAIN RESULTS: In vehicle-treated pigs, 12% survival
      was recorded at 24 hrs, whereas 83% and 66% survival was recorded in the PJ34
      treated animals at 24 and 96 hrs, respectively (p <.05). PJ34 treatment
      attenuated bacteremia-induced increases in systemic and pulmonary vascular
      resistances. In controls, peritonitis induced rapid increase in plasma tumor
      necrosis factor-alpha. PJ34 treatment significantly attenuated this cytokine
      response. The formation of peroxynitrite and the activation of PARS were
      confirmed in hearts and lungs of the septic pigs by the immunohistochemical
      detection of nitrotyrosine and poly(ADP-ribose), respectively. Inhibition of PARS
      with PJ34 abolished poly(ADP-ribose) formation in septic animals. CONCLUSIONS:
      Treatment with a potent PARS inhibitor improved survival and cardiovascular
      status and attenuated an important mediator component of the inflammatory
      response in a lethal porcine model of sepsis.

PMID- 12006791
TI  - Effect of alcohol on the lactate/pyruvate ratio of recently injured adults.
AB  - OBJECTIVE: To compare the ability of plasma (lactate) and the plasma
      lactate/pyruvate (L/P) ratio to predict shock-related outcome after injury and
      also to examine the influence of plasma ethanol on any relationships found.
      DESIGN: Prospective observational study. SETTING: Emergency departments in the UK
      and the Republic of South Africa. PATIENTS: Blood samples were taken at
      presentation from 232 adult patients 1-23 hrs (median, 3.5 hrs) after sustaining
      an injury or injuries deemed sufficiently severe to require inpatient care.
      MEASUREMENTS: Plasma concentrations of lactate, pyruvate, and ethanol, anatomical
      severity of injury, development of multiple organ failure, and 30-day survival
      were determined. RESULTS: At 90% specificity for predicting subsequent mortality
      and/or multiple organ failure, plasma lactate >or=3.85 mmol/L was 23% (5% to 41%)
      more sensitive than an L/P ratio of >or=42.76. At 90% sensitivity for ruling out
      morbidity, plasma lactate <1.6 mmol/L is 6% (-1% to 13%) more specific than an
      L/P ratio of <14.08. High L/P ratios were noted to be associated with a
      detectable plasma alcohol level. A post hoc regression analysis showed that
      alcohol-positive/-negative status was a much stronger predictor of the L/P ratio
      than was anatomical severity of injury, shock, or time after injury. CONCLUSIONS:
      Plasma lactate alone is a better predictor than the L/P ratio of shock-related
      outcome after injury. The interpretation of L/P ratios after injury is confounded
      in the presence of elevated plasma ethanol.

PMID- 12006792
TI  - Repeat bedside percutaneous dilational tracheostomy is a safe procedure.
AB  - OBJECTIVE: Previous tracheostomy has been considered a relative contraindication
      for percutaneous dilational tracheostomy. The objective of this study was to
      assess the safety of percutaneous dilational tracheostomy in critically ill
      patients with a history of previous tracheostomy. DESIGN: Retrospective, single
      center case series of all consecutive patients requiring repeat tracheostomy for
      continued mechanical ventilatory support. SETTING: Intensive care unit of a
      tertiary-care referral center. SUBJECTS: Fourteen patients (eight female, six
      male) with a median age of 70 yrs (range, 33-94). All patients had previously
      undergone tracheostomy. INTERVENTION: Bedside percutaneous dilational
      tracheostomy. MEASUREMENT AND MAIN RESULTS: Subjects' previous tracheostomies
      dated back between 10 days and 8 yrs. Present intubation time before percutaneous
      dilational tracheostomy varied between 4 and 30 days. Bedside percutaneous
      dilational tracheostomy was performed successfully in all 14 patients by trained
      pulmonologists and surgeons. Eleven patients received an 8-mm and three received
      a 7-mm tracheostomy tube. There were no significant periprocedural complications,
      and no patient required surgical revision. The only postprocedural complication
      was accidental decannulation in one patient, which was managed with repeat
      percutaneous dilational tracheostomy. CONCLUSIONS: Trained physicians can safely
      perform bedside percutaneous dilational tracheostomy after previous tracheostomy.
      Percutaneous dilational tracheostomy offers an alternative to surgical
      tracheostomy in this particular patient population and should not be considered
      contraindicated.

PMID- 12006793
TI  - Transesophageal echocardiography in critically ill patients.
AB  - OBJECTIVE: To evaluate the safety and utility of transesophageal echocardiography
      performed by intensive care physicians in critically ill patients. DESIGN:
      Retrospective chart review. SETTING: A 24-bed multidisciplinary adult intensive
      care unit in a 692-bed tertiary referral teaching hospital. PATIENTS: Two hundred
      fifty-five intensive care patients. INTERVENTIONS: We studied 255 consecutive
      intensive care patients who underwent transesophageal echocardiography between
      January 1996 and January 2000. MEASUREMENTS AND MAIN RESULTS: Three hundred eight
      transesophageal echocardiography studies were successfully performed; the probe
      could not be passed in one patient with a cervical fracture. The indications
      included unexplained hypotension (40%), known or suspected endocarditis (27%),
      assessment of ventricular function (15%), pulmonary edema (5%), source of embolus
      (4%), assessment of aorta (4%), and other (5%). In 67% of hypotensive patients,
      transesophageal echocardiography revealed the cause of hemodynamic instability,
      leading to a management change and improvement in blood pressure in 31%. This
      included surgery in 22% without the need for additional tests. Overall,
      transesophageal echocardiography findings led to a significant change in
      management in 32% of all studies performed. One patient receiving continuous
      positive airways pressure suffered pulmonary aspiration during tracheal
      intubation before transesophageal echocardiography, two patients had hypotension
      associated with sedative medication, and there was one case of oropharyngeal
      bleeding after probe insertion. CONCLUSION: Transesophageal echocardiography when
      performed by intensive care physicians is a safe procedure and provides useful
      information for the evaluation and management of critically ill patients.

PMID- 12006794
TI  - Short-term effects of intravenous benzodiazepines on autonomic neurocardiac
      regulation in humans: a comparison between midazolam, diazepam, and lorazepam.
AB  - OBJECTIVES: To evaluate the effects of intravenously applied diazepam, lorazepam,
      and midazolam on autonomic neurocardiac regulation assessed by standardized
      measurements of heart rate variability. DESIGN: Prospective, randomized clinical
      study. SETTING: University teaching hospital. PATIENTS: Forty-five patients, who
      underwent a gastroscopy, were randomly assigned to intravenous premedication with
      midazolam (5 mg), diazepam (10 mg), or lorazepam (4 mg). Six subjects refused an
      injection and served as nonpremedicated controls. INTERVENTIONS: Serial
      recordings of the 5-min resting heart rate variability were obtained before and
      15 and 30 mins after premedication. Seven benzodiazepine-treated patients
      received intravenous flumazenil (0.5 mg). MEASUREMENTS AND MAIN RESULTS: The
      average doses applied were 0.07 mg/kg for midazolam, 0.13 mg/kg for diazepam, and
      0.06 mg/kg for lorazepam. Fifteen minutes after intravenous benzodiazepines were
      administered, we found an increase in resting heart rate and a reduction of vagal
      tone compared with baseline in all three benzodiazepine-treated subgroups.
      Multivariate analysis (covariate age) of the changes in heart rate variability
      indices over the experimental course revealed a significant reduction in absolute
      high-frequency power with midazolam or diazepam compared with nonpremedicated
      subjects. Moreover, midazolam-treated subjects showed a significantly larger
      reduction in relative high-frequency power not only compared with nontreated
      subjects, but also compared with lorazepam- or diazepam-treated subjects. Vagal
      tone remained reduced compared with baseline even 30 mins after benzodiazepine
      application, however, the resting heart rate decreased toward baseline levels.
      After flumazenil administration, there was a linear correlation between an
      increase in high-frequency power and a corresponding decrease in resting heart
      rate. CONCLUSIONS: Benzodiazepines can influence autonomic neurocardiac
      regulation in man, probably through their interaction with the gamma-aminobutyric
      acidA-receptor chloride ion channel complex. The pattern of findings suggests
      that intravenous midazolam, diazepam, and lorazepam influence human autonomic
      neurocardiac regulation in a biphasic way. First, they cause a reduction of
      central vagal tone, and second, they may decrease the cardiac pacemaker directly.
      Flumazenil completely abolished the autonomic neurocardiac regulation effects of
      benzodiazepines.

PMID- 12006795
TI  - Bispectral index-guided sedation with dexmedetomidine in intensive care: a
      prospective, randomized, double blind, placebo-controlled phase II study.
AB  - OBJECTIVE: To compare dexmedetomidine vs. placebo with respect to the amount of
      additional propofol and morphine used for bispectral index-guided sedation and
      analgesia in mechanically ventilated, intensive care patients after surgery.
      DESIGN: Prospective, randomized, double blind, placebo-controlled, phase II
      clinical trial. SETTING: General surgical and cardiac surgical intensive care
      units. PATIENTS: Thirty patients scheduled for major surgery requiring mechanical
      ventilation for a minimum of 6 hrs were included in the study. INTERVENTIONS:
      Patients were assigned randomly to receive either dexmedetomidine (loading
      infusion, 6.0 microg x kg(-1) x hr(-1) for 10 mins; maintenance infusion, 0.1-0.7
      microg x kg(-1) x hr(-1)) or placebo after intensive care unit admission.
      MEASUREMENTS AND MAIN RESULTS: Sedation was guided by using the
      electroencephalographic parameter bispectral index, a new noninvasive method to
      estimate the level of sedation. We aimed at maintaining bispectral index ranges
      between 60 and 70 during mechanical ventilation before starting weaning, 65 and
      95 during weaning, and 85 to 95 postextubation. Additional sedative and analgesic
      medication was given (propofol and morphine) as clinically indicated and within
      the previously mentioned bispectral index ranges. Patients receiving
      dexmedetomidine required significantly less propofol during mechanical
      ventilation (0.87 +/- 0.21 vs. 1.52 +/- 0.30 mg x kg(-1) x hr(-1); p <.01) and
      weaning (0.17 +/- 0.06 vs. 0.62 +/- 0.21 mg x kg(-1) x hr(-1); p <.001) to
      maintain the target bispectral index range. During study drug administration,
      morphine requirements for dexmedetomidine-treated patients were reduced by 58% (p
      =.05). Hemodynamic stability during weaning and after extubation was better
      maintained in patients receiving dexmedetomidine. CONCLUSIONS: Dexmedetomidine
      reduced propofol requirements and improved hemodynamic stability during
      bispectral index-guided intensive care unit sedation.

PMID- 12006796
TI  - Coincidence of pro- and anti-inflammatory responses in the early phase of severe
      sepsis: Longitudinal study of mononuclear histocompatibility leukocyte antigen-DR
      expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in
      septic and postoperative patients.
AB  - OBJECTIVE: To determine the time course of histocompatibility leukocyte antigen
      (HLA)-DR expression in peripheral blood mononuclear cells and their relationship
      to markers of inflammation, organ function, and outcome during severe sepsis.
      DESIGN: Prospective, longitudinal study. SETTING: University hospital intensive
      care unit. PATIENTS: Twenty-three postoperative patients with severe sepsis and
      26 patients with uneventful postoperative course as well as 24 healthy, age
      matched subjects. INTERVENTIONS: Serum procalcitonin was determined by using an
      immunochemiluminescence assay, and C-reactive protein and leukocyte antigens were
      determined by using flow cytometry over 14 days in parallel with clinical data
      collection. MEASUREMENTS AND MAIN RESULTS: Despite a relative lymphopenia,
      absolute lymphocyte counts and CD4+/CD8+ T-cell ratio in septic patients were
      significantly elevated above normal. Particularly, CD4+ and CD8+ T-cell counts in
      nonsurvivors of sepsis were approximately twice as high as those of survivors.
      Significantly decreased monocytic HLA-DR expression was observed in both
      survivors and nonsurvivors at the onset of severe sepsis. Percentages of HLA-DR+
      lymphocytes, however, were significantly increased during sepsis, especially in
      nonsurvivors. Whereas survivors of sepsis showed a continuous recovery of
      monocytic HLA-DR expression to >or=70% within 10 days, nonsurvivors were
      characterized by a second decrease in monocytic HLA-DR expression after day 7 or
      a permanent suppression (<40%). Peak of systemic inflammatory reaction,
      documented by maximum serum concentrations of procalcitonin and C-reactive
      protein, coincided with the nadir of monocytic HLA-DR expression. Moreover,
      procalcitonin and C-reactive protein as well as scores on the Acute Physiology
      and Chronic Health Evaluation II and Sepsis Organ Failure Assessment were
      inversely correlated with the monocytic HLA-DR expression. CONCLUSIONS: Decreases
      in monocytic HLA-DR expression occurred simultaneously with signs of
      hyperinflammation as early as the onset of severe sepsis and usually developed in
      opposite directions than inflammatory markers and sepsis severity scores.

PMID- 12006797
TI  - Transcutaneous carbon dioxide monitoring during high-frequency oscillatory
      ventilation in infants and children.
AB  - OBJECTIVE: Continuous monitoring of ventilation during mechanical ventilation may
      improve patient management by facilitating proactive rather than reactive
      ventilator adjustments and may decrease the need for repeated arterial blood gas
      analysis. Because of their more critical pulmonary status, patients requiring
      high-frequency oscillatory ventilation may especially benefit from continuous
      monitoring. DESIGN: Prospective evaluation of the correlation between
      transcutaneous CO2 (TC(CO2)) and PaCO2 values. SETTING: Tertiary care pediatric
      intensive care unit. PATIENTS: Fourteen pediatric patients receiving high
      frequency oscillatory ventilation for severe respiratory failure. INTERVENTIONS:
      TC(CO2) was monitored continuously and compared with PaCO2 values when arterial
      blood gas analysis was performed. MEASUREMENTS AND MAIN RESULTS: One hundred
      sample sets were obtained from 14 patients age 1 day to 16 yrs (3.5 +/- 4.6 yrs)
      and weighing 3.1-85 kg (18.5 +/- 22.4 kg). The mean absolute difference between
      PaCO2 and TC(CO2) was 2.8 +/- 1.9 mm Hg. Regression analysis of TC(CO2) and PaCO2
      values revealed a slope of 1.04, an r value of.96, and an r value of.94 (p
      <.0001). Bland-Altman analysis revealed a bias of 2.1 mm Hg with a precision of
      2.7 mm Hg when TC(CO2) was compared with PaCO2 for the entire group. In the
      subgroup where PaCO2 was <or=50 mm Hg, the bias was 1.9 with a precision of 2.8,
      whereas when PaCO2 was >50 mm Hg, the bias was 2.3 with a precision of 2.6 (p =
      not significant). CONCLUSIONS: TC(CO2) monitoring provides an accurate and
      clinically acceptable estimate of PaCO2 over a wide range of CO2 values in
      pediatric patients during high-frequency oscillatory ventilation.

PMID- 12006798
TI  - Legionnaire's disease associated with acute encephalitis and arrhythmia.
AB  - OBJECTIVE: To report an unusual, life-threatening combination of neurologic,
      cardiac, and gastrointestinal symptoms in the presence of a community-acquired
      pneumonia. DESIGN: Case report. SETTING: University hospital. PATIENT: Previously
      healthy young male. INTERVENTION: Diagnostic fiberoptic bronchoscopy, lumber
      puncture, magnetic resonance imaging of the brain, and institution of systemic
      antibiotics. MAIN RESULT: Gradual clinical improvement of a multiple-system
      illness. CONCLUSION: Legionellosis should be considered in the differential
      diagnosis of patients presenting with neurologic, cardiac, and gastrointestinal
      symptoms, particularly in the presence of radiographic pneumonia. Furthermore,
      Legionella meningoencephalitis may present with findings on magnetic resonance
      imaging previously thought to be characteristic of herpes encephalitis.

PMID- 12006799
TI  - Significant increase of activated partial thromboplastin time by heparinization
      of the radial artery catheter flush solution with a closed arterial catheter
      system.
AB  - OBJECTIVE: Evaluate whether the use of a heparinized flush for an arterial
      catheter with a closed-loop blood sampling system leads to erroneous coagulation
      studies. DESIGN: Prospective study. SETTING: Twenty-two-bed surgical adult
      intensive care unit in a university hospital. PATIENTS: Sixty patients, 30 in
      each phase of the study. INTERVENTIONS: Phase 1: coagulation studies on a blood
      sample from a venous puncture and an arterial blood sample from an arterial
      catheter with heparinized flush. Phase 2: the same protocol but the arterial
      catheter was flushed with saline. MEASUREMENTS: Activated partial thromboplastin
      time, fibrinogen, percentage of prothrombin time, and international normalized
      ratio of prothrombin time on the venous and arterial samples. MAIN RESULTS:
      Activated partial thromboplastin time in the arterial blood samples taken from an
      arterial catheter with heparinized flush was significantly prolonged compared
      with the venous controls. This was not the case in blood samples from an arterial
      catheter with saline flush. The magnitude of this difference found by the Bland
      and Altman analysis was clinically significant. In 23.3% of the patients in phase
      1, there was a difference of >50% between the arterial and venous sampled
      activated partial thromboplastin time, compared with 0% of the patients in phase
      2 (p =.018). There was no difference between the venous and the arterial blood
      samples for the non-heparin-sensitive coagulation studies in both phases of the
      study. An explanation for these findings could be that there was release of
      heparin bound to the arterial catheter into the blood sample. CONCLUSION: A
      heparinized flush solution for the arterial catheter, when used together with a
      closed-loop blood sampling system, leads to erroneous results of heparin
      sensitive coagulation studies. Heparin-sensitive coagulation studies, therefore,
      should not be analyzed on blood samples from such a system if a heparinized flush
      solution is used.

PMID- 12006800
TI  - Prospectively validated prediction of physiologic variables and organ failure in
      septic patients: The Systemic Mediator Associated Response Test (SMART).
AB  - OBJECTIVE: Conventional outcomes research provides only percentage risk of such
      end points as mortality rate, utilization of resources, and/or broad groupings of
      multiple organ system dysfunction. These prognostications generally are not
      applicable to individual patients. The purpose of the present study was to
      determine whether the Systemic Mediator Associated Response Test (SMART)
      methodology could identify interactions among demographics, physiologic
      variables, standard hospital laboratory tests, and circulating cytokine
      concentrations that predicted continuous and dichotomous dependent clinical
      variables, in advance, in individual patients with severe sepsis and septic
      shock, and whether these independent variables could be integrated into
      prospectively validated predictive models. DESIGN: Data review and multivariate
      stepwise logistic regression. SETTING: University research laboratory. PATIENTS:
      Three hundred three patients with severe sepsis or septic shock who comprised the
      placebo arm of a multiple-institution clinical trial, who were randomly separated
      into a model building training cohort (n = 200) and a predictive cohort (n =
      103). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From baseline data and
      baseline plus serial input, including patient demographics, hospital laboratory
      tests, and plasma concentrations of interleukin-6, interleukin-8, and granulocyte
      colony stimulating factor, multiple regression models were developed that
      predicted clinically important continuous dependent variables quantitatively, in
      individual patients. Multivariate stepwise logistic regression was used to
      develop models that prognosticated dichotomous dependent end points. Data from
      individual patients in the predictive cohort were inserted into each predictive
      model for each day, with prospective validation accomplished by simple linear
      regression of individual predicted vs. observed values for continuous dependent
      variables, and by establishing the receiver operator characteristics area under
      the curve for logistic regression models that predicted dichotomous end points.
      Of SMART models for continuous dependent variables, 100 of 143 (70%) were
      validated at r values >.7 through day 3, and 184 of 259 (71%) above r =.5 through
      day 5. SMART predictions of dichotomous end points achieved receiver operator
      characteristics areas under the curve >.7 for up to 84% of the equations in the
      first week. Many SMART models for both continuous and dichotomous dependent
      variables were validated at clinically useful levels of accuracy as far as 28
      days after baseline. CONCLUSIONS: SMART integration of demographics, bedside
      physiology, hospital laboratory tests, and circulating cytokines predicts organ
      failure and physiologic function indicators in individual patients with severe
      sepsis and septic shock.

PMID- 12006801
TI  - Genomic polymorphism within interleukin-1 family cytokines influences the outcome
      of septic patients.
AB  - OBJECTIVE: To determine the allele frequencies and genotype distribution of
      interleukin-1alpha, interleukin-1beta, and interleukin-1 receptor antagonist gene
      polymorphism in septic patients. DESIGN: Prospective, consecutive entry study of
      septic patients in a general intensive care unit. SETTING: A 14-bed general
      intensive care unit of a university hospital. PATIENTS: Sixty patients with
      diagnosis of sepsis, admitted to the intensive care unit between 1997 and 1999.
      INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The polymorphic regions within
      intron 6 of interleukin-1alpha gene containing variable numbers of a tandem
      repeat (VNTR) of 46 base pairs, and intron 2 of interleukin-1 receptor antagonist
      gene containing VNTR of 86 base pairs, were amplified by means of polymerase
      chain reaction. Alleles A1-4 and RN1-4 were identified according to the size of
      amplified DNA product. The region containing the AvaI polymorphic site at
      position -511 of interleukin-1beta gene was amplified by polymerase chain
      reaction and subsequently digested with AvaI restriction enzyme. The allele
      frequencies of interleukin-1 receptor antagonist RN2 and genotype RN2/2 were
      increased in 60 septic patients compared with normal controls (p <.01 and.05,
      respectively). Allele frequencies or genotype distribution of interleukin-1alpha
      VNTR gene polymorphism and interleukin-1beta AvaI polymorphism did not differ
      between septic patients and normal controls. In addition, genotypes A2/2, B2/2,
      and RN2/2 were associated with a significantly higher mortality rate (70% to 80%)
      in septic patients. Patients with any two of the three alleles (i.e., A2, B2, and
      RN2) suffered from much more severe sepsis (as measured by the Acute Physiology
      and Chronic Health Evaluation II and Multiple Organ Dysfunction Syndrome score)
      and a higher mortality rate (55% to 65%), whereas septic patients with genotypes
      A1/1, B1/1, or RN1/1 showed a much lower mortality rate (0% to 13%). CONCLUSIONS:
      Allele interleukin-1RN2, but not interleukin-1A or interleukin-1B gene
      polymorphism, was associated with susceptibility to sepsis. Alleles A2, B2, and
      RN2 might be important high-risk genetic markers for sepsis.

PMID- 12006802
TI  - Osmolar gap hyponatremia in critically ill patients: evidence for the sick cell
      syndrome?
AB  - OBJECTIVE: Accumulation of nondiffusible solutes in plasma leads to
      redistribution hyponatremia with an increased osmolar gap (i.e., the difference
      between measured and calculated osmolality). In critically ill patients,
      intracellular solutes may leak out of the cell because of an increased membrane
      permeability and may lead to redistribution hyponatremia with increased osmolar
      gap, a concept called the "sick cell syndrome." The aims of this prospective
      study were to determine whether an increased osmolar gap related to endogenous
      solutes accumulation was present in intensive care patients with true
      hyponatremia and to identify the solutes accounting for this increased osmolar
      gap. SETTING: A 14-bed medical intensive care unit in an 821-bed university
      hospital. DESIGN: A 20-wk prospective observational study. PATIENTS: Fifty-five
      consecutive patients with a measured plasma sodium concentration <or=130 mmol/L
      (mean +/- sd, 126 +/- 6 mmol/L) were automatically identified by the Biochemistry
      Department. Patients were excluded in the case of reduced plasma water content
      resulting from hyperlipidemia or hyperproteinemia, in the case of hyperglycemia,
      or if exogenous compounds known to increase the osmolar gap were present.
      INTERVENTIONS: Plasma osmolar gap was calculated. MEASUREMENTS AND MAIN RESULTS:
      Plasma osmolar gap was considered significant if >10 mosm/kg. Total plasma amino
      acid concentration also was measured. Organ dysfunctions were assessed with the
      Sequential Organ Failure Assessment. Thirty of the 55 patients (54%) had an
      osmolar gap >10 mosm/kg (17.2 +/- 7.1 mosm/kg). Sequential Organ Failure
      Assessment score was significantly higher in the osmolar gap patients (6.4 +/-
      3.2 vs. 4.5 +/- 2.0; p =.015). No difference of amino acids concentration was
      observed between osmolar gap and non-osmolar gap patients, and no correlation was
      observed between osmolar gap and amino acid concentration. Accumulation of ketone
      bodies and lactic acid was also unlikely. During correction of hyponatremia in
      osmolar gap patients, a significant decrease of plasma osmolar gap was observed
      and a statistically significant inverse relationship was demonstrated between
      osmolar gap decrease and plasma sodium concentration increase. CONCLUSION:
      Hyponatremia with increased osmolar gap related to endogenous solutes
      accumulation is observed frequently in hyponatremic intensive care patients,
      especially in patients with the most severe organ dysfunctions. The nature of the
      endogenous solutes accounting for the increased osmolar gap remains to be
      determined. Simultaneous correction of sodium and osmolar gap suggests a causal
      link between increased osmolar gap and hyponatremia and may support the concept
      of sick cell syndrome.

PMID- 12006803
TI  - Failure of neutrophil chemotactic function in septic patients.
AB  - OBJECTIVE: To investigate the in vitro chemotactic function of neutrophils
      obtained from patients with sepsis. DESIGN: Prospective study in which purified
      neutrophils obtained from septic patients and nonseptic control volunteers were
      assayed for chemotactic function induced by N-formyl-L-methionyl-L-leucyl-L
      phenylalanine (FMLP) and leukotriene B4. The sera nitrate concentrations also
      were quantified. SETTING: University hospital. PATIENTS: Twenty patients with
      sepsis caused by different infectious foci. INTERVENTIONS: Routine blood tests,
      blood or other site cultures, blood collection for neutrophil purification sera
      collection for nitrate assay. MEASUREMENTS AND MAIN RESULTS: Neutrophils from
      septic patients exhibited significantly less chemotactic activity than
      neutrophils obtained from healthy volunteers, in response to FMLP (93.4 +/- 6.6
      vs. 51 +/- 8.3 migrated neutrophils) and leukotriene B4 (90.2 +/- 10 vs. 42.4 +/-
      11.6 migrated neutrophils) stimuli, in a microchemotaxis chamber assay. The
      impaired chemotaxis occurred mainly in neutrophils from nonsurvivor patients. The
      extent of neutrophil chemotaxis inhibition (survivor/nonsurvivor) was
      33.43%/61.67% and 43.4%/86.98%, in response to FMLP and leukotriene B4,
      respectively. Increased serum nitrate (micromoles of NO2 + NO3) concentrations
      were detected in septic patients, compared with controls, but no differences were
      found between survivor (91.84 +/- 14.12) and nonsurvivor (102.6 +/- 17.36)
      groups. CONCLUSIONS: Septic patients present suppressed neutrophil chemotactic
      responses to FMLP and leukotriene B4 stimuli compared with healthy controls. This
      is accompanied by increased serum concentrations of nitrate. The impairment of
      neutrophil chemotaxis was observed mainly in the cells obtained from nonsurvivor
      patients and may thus be an additional factor contributing to disease outcome.

PMID- 12006804
TI  - Bedside microdialysis: a tool to monitor cerebral metabolism in subarachnoid
      hemorrhage patients?
AB  - OBJECTIVE: To analyze the time course and changes of cerebral microdialysis
      parameters after aneurysmal subarachnoid hemorrhage (SAH) in respect to the
      clinical course (asymptomatic, delayed, and acute ischemic neurologic deficits)
      to evaluate the method of bedside microdialysis in these patients. DESIGN:
      Prospective, controlled study during a 3-yr period. SETTING: Neurosurgical
      intensive care unit at a primary level university hospital, supervised and
      staffed by members of both the department of neurosurgery and the department of
      anesthesiology and intensive care medicine. PATIENTS: Ninety-seven patients (51
      females/21 males; 52 +/- 13 yrs; World Federation of Neurological Surgeons Scale
      grades 0-5) after aneurysmatic SAH. MEASUREMENTS AND MAIN RESULTS: A
      microdialysis catheter (CMA 100) was inserted into the region most likely to be
      affected by vasospasm directly after aneurysm clipping, connected to a pump, and
      perfused with Ringer solution (0.3 microL/min). The dialysates were collected
      hourly and analyzed at the bedside for glucose, lactate, lactate-pyruvate ratio,
      glutamate, and glycerol (CMA 600). Patients were classified according to clinical
      presentation as being asymptomatic or having acute (AIND) or delayed (DIND)
      ischemic neurologic deficits. DIND patients (n = 18) had significantly higher
      lactate and glutamate concentrations on days 1-8 post-SAH and a higher lactate
      pyruvate ratio on days 3-8 post-SAH compared with asymptomatic patients (n = 57;
      p <.025). Glucose and glycerol levels did not differ in asymptomatic and DIND
      patients. AIND patients (n = 22) had the worst metabolic pattern: the
      extracellular glucose concentration was low, whereas the lactate, lactate
      pyruvate ratio, glutamate, and glycerol levels were significantly elevated
      compared with asymptomatic and DIND patients. In 83% of the DIND patients, the
      changes in metabolites indicative of cerebral ischemia preceded the onset of
      symptomatic vasospasm. All DIND patients clinically improved in their Glasgow
      Coma Scale scores with induced hypertension, intentional hypervolemia, and/or
      hemodilution therapy (p =.01). CONCLUSION: Cerebral bedside microdialysis is a
      safe and promising technique for monitoring (impending) regional cerebral
      ischemia. The dialysate changes can indicate early the onset of delayed
      neurologic deterioration and are in good accordance with the clinical course of
      SAH patients. In the future, this technique may be used to monitor the efficacy
      of the intensive care therapy of these patients.

PMID- 12006805
TI  - Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose)
      synthetase: potent cytoprotective and antishock agents.
AB  - OBJECTIVE: To synthesize novel inhibitors of the nuclear enzyme poly(adenosine 5'
      diphosphate [ADP]-ribose) synthetase (PARS), also known as poly(ADP-ribose)
      polymerase (PARP), and to test them in in vitro models of oxidant-induced
      cytotoxicity and in endotoxin and splanchnic occlusion-reperfusion-induced shock.
      DESIGN: Randomized, prospective laboratory study. SETTING: Research laboratory.
      SUBJECTS: Murine macrophages, thymocytes, and endothelial cells; Balb/c mice and
      Wistar rats. INTERVENTIONS: Macrophages and endothelial cells were treated with
      peroxynitrite and bleomycin to induce PARS activation, and thymocytes were
      treated with peroxynitrite to induce cell necrosis. Novel PARS inhibitors were
      synthesized and used to reduce PARS activation and to reverse cytotoxicity.
      Balb/c mice were subjected to splanchnic occlusion and reperfusion and were
      pretreated with various doses (1-10 mg/kg intraperitoneally) of PJ34, a selected,
      potent, water-soluble PARS inhibitor. The passage of fluorescein isothiocyanate
      conjugated dextran (4 kDa) was analyzed in everted gut ileal sacs incubated ex
      vivo as an index of gut permeability. Wistar rats were subjected to Escherichia
      coli bacterial lipopolysaccharide (40 mg/kg intraperitoneally). PJ34 was also
      used at 10 mg/kg intraperitoneally, 1 hr before lipopolysaccharide or at 25 mg/kg
      intraperitoneally 1 hr after lipopolysaccharide treatment. Serum concentrations
      of indicators or multiple organ injury, concentrations of various proinflammatory
      mediators, and tissue concentrations of myeloperoxidase and malondialdehyde were
      measured. In addition, survival rates and vascular contractile and relaxant
      responses were recorded. MEASUREMENTS AND MAIN RESULTS: Appropriate modifications
      of the phenanthridinone core structure yielded significant increases in the
      potency of the compounds, both as PARS inhibitors and as cytoprotective agents.
      The compound N-(6-oxo-5,6-dihydro-phenanthridin-2-yl) -N,N-dimethylacetamide
      (designated as PJ34) was one of the potent PARS inhibitors of the series, and it
      dose-dependently protected against thymocyte necrosis, with a half-maximal
      restoration of cell viability of 35 nM and complete protection at 200 nM. PARS
      activation also was visualized by immunohistochemistry and was dose-dependently
      suppressed by PJ34. The effect of PJ34 was dose-dependently reversed by excess
      nicotinamide adenine dinucleotide (oxidized). The PARS inhibitors dose
      dependently suppressed proinflammatory cytokine and chemokine production and
      restored viability in immunostimulated macrophages. PJ34 was selected for the
      subsequent in vivo studies. PJ34 significantly protected against splanchnic
      reperfusion-induced intestinal hyperpermeability in the mouse. PJ34 reduced peak
      plasma concentrations of tumor necrosis factor-alpha, interleukin-1beta, and
      nitrite/nitrate in the plasma of lipopolysaccharide-treated rats. PJ34
      ameliorated the lipopolysaccharide-induced increases in indexes of liver and
      kidney failure and concentrations of myeloperoxidase and malondialdehyde in the
      lung and gut. Lipopolysaccharide elicited vascular dysfunction, which was
      normalized by PJ34. Lipopolysaccharide-induced mortality was reduced by PJ34
      (both pre- and posttreatment). CONCLUSIONS: The novel series of phenanthridinone
      PARS inhibitors have potent cytoprotective effects in vitro and significant
      protective effects in shock and reperfusion injury in rodent models in vivo.

PMID- 12006806
TI  - In vitro and in vivo intrapulmonary distribution of fluorescently labeled
      surfactant.
AB  - OBJECTIVE: To determine the distribution of endotracheally administered
      surfactant at the alveolar level in an animal model of acute respiratory distress
      syndrome. DESIGN: Prospective, randomized animal study. SETTING: Research
      laboratory of a university hospital. SUBJECTS: Seventy-one male Sprague-Dawley
      rats, weighing 330-370 g. INTERVENTIONS: To measure surfactant distribution in
      vitro, a glass trough mimicking dichotomic lung anatomy was used to determine the
      spreading properties of bovine lung surfactant extract supplemented with
      fluorescent Bodipy-labeled surfactant protein B. To measure surfactant
      distribution in vivo, rats were anesthetized, and lipopolysaccharide was
      aerosolized (12 mg/kg body weight) to induce lung injury resembling acute
      respiratory distress syndrome; in control rats, buffered saline was aerosolized.
      Twenty-four hours later rats were anesthetized, tracheotomized, and mechanically
      ventilated (peak airway pressure = 20 mbar; positive end-expiratory pressure = 6
      mbar; inspiration time = expiration time = 0.6 sec; Fio2 = 50%). Surfactant
      (bovine lung surfactant extract, supplemented with fluorescent Bodipy-labeled
      surfactant protein B; 50 mg/kg body weight) was applied as a bolus; in control
      rats, saline was administered as a bolus. Rats were ventilated for 5, 15, 30, or
      60 mins (n = 8 or 9 for each group). Then, lungs were excised and sliced. Lung
      slices, divided into aerated (open), underinflated (dystelectatic), or collapsed
      (atelectatic) alveolar areas, were examined by both light and fluorescence
      microscopy. RESULTS: In vitro experiments revealed that surfactant spread
      independent of glass trough geometry and lowered the surface tension to
      equilibrium values (25 mN/m) within a few seconds. In vivo experiments showed
      that administered surfactant distributed preferentially into underinflated and
      aerated alveolar areas. Furthermore, surfactant distribution was not affected by
      length of mechanical ventilation. CONCLUSIONS: When conventional mechanical
      ventilation was used in lipopolysaccharide-induced lung injury, surfactant
      preferentially distributed into underinflated and aerated alveolar areas. Because
      surfactant rarely reached collapsed alveolar areas, methods aiding in alveolar
      recruitment (e.g., open lung concept or body positioning) should precede
      surfactant administration.

PMID- 12006807
TI  - n-3 Polyunsaturated fatty acid-enriched diet does not protect from liver injury
      but attenuates mortality rate in a rat model of systemic endotoxemia.
AB  - OBJECTIVE: We investigated the potential of dietary fish oil containing n-3
      polyunsaturated fatty acids to attenuate hepatic injury and mortality rate of
      rats in response to systemic endotoxemia. DESIGN: Prospective, randomized,
      controlled animal study. SETTING: University laboratory. SUBJECTS: A total of 43
      male Sprague Dawley rats. INTERVENTIONS: Rats were fed either fish oil supplement
      or regular standard lab chow. After 8 wks of feeding, each diet group was
      subjected to a single exposure of lipopolysaccharide (Escherichia coli, 10 mg/kg
      intravenously) or saline. Hepatic microvascular response and liver injury were
      assessed by in vivo analysis of Kupffer cell phagocytic activity, leukocyte
      endothelial cell interaction, nutritive sinusoidal perfusion failure, and
      parenchymal cell apoptosis (intravital fluorescence epi-illumination technique)
      as well as bile flow, serum liver enzyme activities, and tissue histomorphology.
      MEASUREMENTS AND MAIN RESULTS: In animals fed a standard diet, livers at 16 hrs
      after lipopolysaccharide-exposure exhibited depressed Kupffer cell phagocytic
      activity, enhanced hepatic microvascular leukocyte activation, leukocytic tissue
      infiltration, sinusoidal perfusion failure, and parenchymal cell apoptosis.
      Hepatic microvascular injury was further accompanied by reduced bile flow and
      enhanced liver enzyme release. The fish oil enriched diet did not significantly
      change the multiple features of endotoxemia-associated liver injury; however, it
      maintained arterial blood pressure, systemic leukocyte count, and acid base
      balance and showed a tendency toward improved survival on lipopolysaccharide
      exposure with a 16 hr-survival rate of 80% (p =.06 vs. survival rate of 40% in
      animals fed a regular diet). Moreover, slightly increased serum concentrations of
      interleukin-10 coincided with enhanced concentrations of interleukin-6 in fish
      oil fed endotoxemic animals. Healthy, non-lipopolysaccharide-exposed, fish oil
      fed animals did not differ from those fed with the regular diet, except for
      dampened Kupffer cell phagocytic activity. CONCLUSIONS: Fish oil feeding does not
      protect from local endotoxemia-induced hepatic microvascular dysfunction.
      However, dietary modulation of inflammatory mediator response by macrophages,
      constituting an appropriate immune response, could add to the survival advantage
      seen in fish oil-fed animals on exposure to lipopolysaccharide.

PMID- 12006808
TI  - Effect of growth hormone on muscle and liver protein synthesis in septic rats
      receiving glutamine-enriched parenteral nutrition.
AB  - OBJECTIVE: Administration of recombinant human growth hormone (rhGH) to
      critically ill adults in an attempt to attenuate catabolism was associated with
      increased morbidity and mortality. Possible explanations included inhibition of
      glutamine release from skeletal muscle and consequent restriction of splanchnic
      glutamine supply. In this study, we examined the effects of rhGH on plasma
      glutamine levels and on muscle and liver glutamine concentrations and protein
      synthesis rates in sepsis. We investigated the possibility that administration of
      supplemental glutamine might ameliorate any adverse effects of rhGH. DESIGN:
      Prospective study in rats rendered septic by cecal ligation and puncture.
      SETTING: University hospital laboratory. SUBJECTS: A total of 78 male Wistar rats
      in six groups. INTERVENTIONS: Animals received 6-hr tail vein infusions,
      commencing 18 hrs after cecal ligation and puncture, of either (a) 0.9% sodium
      chloride, (b) a standard parenteral nutrition (PN) solution without glutamine, or
      (c) an isocaloric, isonitrogenous PN solution with glutamine. PN groups received
      400 microg rhGH or equivolume 0.9% sodium chloride vehicle in a divided
      subcutaneous and intravenous dose at PN commencement. Sacrifice was at the end of
      the infusion period. A further group was unoperated and uninfused and killed at
      24 hrs as baseline controls. MEASUREMENTS AND MAIN RESULTS: Glutamine
      concentrations were measured by fluorometry. Protein synthesis in muscle and
      liver was measured by a "flooding-dose" technique employing L-[4-H]phenylalanine.
      Plasma glutamine was increased after cecal ligation and puncture except in the
      saline and glutamine with rhGH animals. Muscle glutamine was reduced after cecal
      ligation and puncture and was significantly lower in animals receiving standard
      PN with rhGH vs. saline alone. Liver glutamine was increased in animals receiving
      saline and those receiving standard PN with rhGH. PN, with or without glutamine,
      increased muscle protein synthesis, and the administration of rhGH tended to
      further increase this effect. Neither PN, glutamine, nor rhGH had an effect on
      the increased liver protein synthesis characteristic of sepsis. CONCLUSIONS: In
      sepsis, increased muscle protein synthesis with PN and rhGH administration is not
      associated with increased muscle glutamine levels. Administration of rhGH does
      not result in reduced liver glutamine levels or rates of hepatic protein
      synthesis. PN containing glutamine was no more efficacious than standard PN at
      increasing muscle protein synthesis.

PMID- 12006809
TI  - Tracheal pressure control provides automatic and variable inspiratory pressure
      assist to decrease the imposed resistive work of breathing.
AB  - OBJECTIVE: To evaluate the operation of a continuous positive airway pressure
      system by using tracheal airway pressure (PT) as the control signal for system
      operation (i.e., tracheal pressure control). DESIGN: Repeated measures. SETTING:
      University research laboratory. SUBJECTS: Twelve anesthetized, spontaneously
      breathing swine. INTERVENTIONS: Subjects were intubated and connected to a
      tracheal pressure control system (5 cm H2O continuous positive airway pressure).
      Varying inspiratory flow demands and degrees of partial endotracheal tube
      occlusion (25%, 50%, and 75%) were studied. Tracheal pressure control was
      compared with a conventionally controlled system (pressure from breathing circuit
      Y-piece [PY] used as control signal) during endotracheal tube occlusion.
      MEASUREMENTS AND RESULTS: Imposed resistive work of breathing (work to
      spontaneously inhale through endotracheal tube and ventilator circuit), work by
      ventilation system assisting inhalation, PT, PY, tidal volume, and inspiratory
      flow demands were measured. As inspiratory flow demands increased (range, 0.2-2.3
      L/sec), pressure assist increased automatically (range, 5-40 cm H2O) as well as
      work of breathing by ventilation system assisting inhalation (range, 0.2-2.5
      J/L). Imposed resistive work of breathing was nullified at the lower and was
      negligible at the higher flow demands. During endotracheal tube occlusion with a
      conventionally controlled system, PY was unchanged, whereas PT decreased (up to 
      15 cm H2O) and imposed resistive work of breathing increased (up to 1.05 J/L).
      With tracheal pressure control, PY increased automatically (range, 8-52 cm H2O),
      whereas PT varied slightly (range, 2 to -4.6 cm H2O). Imposed resistive work of
      breathing was negligible (range, 0-0.2 J/L). Breathing circuit pressure (PY), not
      pulmonary airway pressure (PT), increased significantly during tracheal pressure
      control. CONCLUSIONS: Tracheal pressure control results in automatic and variable
      levels of pressure assist to decrease imposed resistive work of breathing under
      conditions of varying spontaneous inspiratory flow demands and endotracheal tube
      occlusion. Conventional systems are potentially flawed when PY is used as the
      control signal because they do not function in this manner and do not accurately
      assess pulmonary airway pressure.

PMID- 12006810
TI  - Migration of human monocytes in response to procalcitonin.
AB  - OBJECTIVE: Circulating serum levels of procalcitonin rise significantly during
      bacterial infection. Because calcitonin is known to be a monocyte
      chemoattractant, we investigated whether procalcitonin, a prohormone of
      calcitonin, also affects leukocyte migration. DESIGN: Prospective, controlled in
      vitro study. SETTING: University research laboratories. INTERVENTIONS: Forearm
      venous blood polymorphonuclear neutrophils and monocytes were isolated from
      healthy human donors. Cell migration was assessed in a blindwell chemotaxis
      chamber. The distance of migration into filter micropores was measured. To
      biochemically confirm functional data on cell migration, effects of procalcitonin
      on cellular levels of cyclic adenosine monophosphate were measured by high
      performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Both
      procalcitonin and calcitonin elicited dose-dependent migration of monocytes at
      concentrations from the femtomolar to the micromolar range. Neutrophils did not
      migrate toward procalcitonin or calcitonin, nor was their oxygen free radical
      release affected as measured fluorimetrically. Checkerboard analysis of monocyte
      locomotion revealed procalcitonin-induced migration as true chemotaxis.
      Pretreatment of monocytes with procalcitonin or calcitonin rapidly deactivated
      their migratory response to formyl-Met-Leu-Phe, and both also induced homologous
      deactivation of migration. Procalcitonin elevated levels of cyclic adenosine
      monophosphate in monocytes. CONCLUSIONS: In vitro procalcitonin is a monocyte
      chemoattractant that deactivates chemotaxis in the presence of additional
      inflammatory mediators. Procalcitonin stimulates cyclic adenosine monophosphate
      production in monocytes, suggesting that its action may be specific and
      comparable with calcitonin, which exerts similar functions.

PMID- 12006811
TI  - Omeprazole treatment diminishes intra- and extracellular neutrophil reactive
      oxygen production and bactericidal activity.
AB  - OBJECTIVE: Neutrophils play a crucial role in host defense against infectious
      disease. The objective was to analyze the effect of omeprazole treatment on
      indexes of neutrophil function in healthy subjects. DESIGN: Open. SETTING:
      University hospital. SUBJECTS: Ten healthy subjects. INTERVENTION: Analysis of
      blood samples before and after omeprazole administration. MEASUREMENTS AND MAIN
      RESULTS: Neutrophil Escherichia coli phagocytosis was assessed by microscopy and
      flow cytometry. Intracellular production of reactive oxygen intermediates was
      measured by flow cytometry. Extracellular reactive oxygen intermediate production
      was assessed with a cytochrome c reduction assay. Neutrophil bactericidal
      capacity and intracellular concentrations of Ca2+ were determined by fluorometry.
      Four hours after a single 40-mg dose of omeprazole, intra- and extracellular
      reactive oxygen intermediate production by neutrophils was significantly reduced
      compared with pretreatment values: -30% (24% to 42%) (median and range) and -22%
      (21% to 68%; p <.05 for both). The intracellular Ca2+ concentrations in resting
      neutrophils were significantly increased (+33%, 21% to 39%, compared with
      pretreatment concentrations, p <.001) and neutrophilic bactericidal activity was
      decreased (-30%, 19% to 47%, compared with pretreatment concentrations, p
      <.0001). Intracellular Ca2+ concentrations correlated with intracellular reactive
      oxygen intermediate production and neutrophilic bactericidal capacity (r =.730
      and r =.618, p <.05 for both, respectively). In contrast, phagocytosis rates were
      not impaired by omeprazole. CONCLUSIONS: Our results imply that omeprazole
      impairs production of reactive oxygen intermediates by neutrophils. Whether
      specific impairments of neutrophil host defenses occur in vivo remains uncertain.
      Reduced bactericidal activity is associated with an increase of intracellular
      Ca2+ concentrations in resting neutrophils.

PMID- 12006812
TI  - Effect of perfluorocarbon (perfluorooctyl bromide) vapor on tidal volume
      measurement during partial liquid ventilation.
AB  - OBJECTIVE: To compare measured tidal volumes with and without perfluorocarbon
      (perfluorooctyl bromide) vapor, by using tidal volumes in the range suitable for
      neonates ventilated with partial liquid ventilation. We also aimed to determine
      the correction factor needed to calculate tidal volumes measured in the presence
      of perfluorooctyl bromide vapor. DESIGN: Prospective, experimental study.
      SETTING: Neonatal research laboratory. INTERVENTIONS: Reproducible tidal volumes
      from 5 to 30 mL were produced with a rodent ventilator and drawn from humidifier
      chambers immersed in a water bath at 37 degrees C. Control tidal volumes were
      drawn from a chamber containing oxygen and water vapor, and the perfluorocarbon
      tidal volumes were drawn from a chamber containing oxygen, water vapor, and
      perfluorooctyl bromide vapor. MEASUREMENTS AND MAIN RESULTS: Tidal volumes were
      measured by a VenTrak respiratory mechanics monitor with a neonatal flow sensor
      and a Drager pneumotachometer attached to a Drager neonatal ventilator. All tidal
      volumes measured with perfluorooctyl bromide vapor were increased compared with
      control. The VenTrak-measured tidal volumes increased by 1.8% to 3.5% (an overall
      increase of 2.2%). The increase was greater with the Drager hot-wire anemometer:
      from 2.4% to 6.1% (an overall increase of 5.9%). Regression equations for mean
      control tidal volumes (response, Y) vs. mean perfluorooctyl bromide tidal volumes
      (predictor, X) are as follows: for the VenTrak, Y = -0.026 + (0.978 x X), r
      =.9999, p <.0001; and for the Drager, Y = 0.251 + (0.944 x X), r =.9996, p
      <.0001. CONCLUSIONS: The presence of perfluorooctyl bromide vapor in the gas
      flowing through pneumotachometers gives falsely high tidal volume measurements.
      An estimate of the true tidal volume allowing for the presence of perfluorooctyl
      bromide vapor can be made from regression equations. Any calculation of lung
      mechanics must take into account the effect of perfluorooctyl bromide vapor on
      the measurement of tidal volume.

PMID- 12006813
TI  - Neuroprotective effects of hyperthermic preconditioning on infarcted volume after
      middle cerebral artery occlusion in rats: role of adenosine receptors.
AB  - OBJECTIVE: There are still only a limited number of studies regarding the
      neuroprotective effects of hyperthermic preconditioning on regional brain
      ischemia or regarding the role of adenosine A1 receptors in such pretreatment. We
      examined the effects of hyperthermic pretreatment on infarcted volume after
      middle cerebral artery occlusion (MCAO), as well as the contribution of A1
      receptors, to the responses in rats. DESIGN: Prospective, randomized animal
      study. SETTINGS: An animal research laboratory in a medical university. SUBJECTS:
      Male Wistar rats (200-250 g). INTERVENTION: All animals were anesthetized with
      isoflurane during each pretreatment, as well as for MCAO. The animals were
      assigned as follows: (i) sham-control group (n = 8), which was maintained at
      normothermia (37 +/- 0.2 degrees C pericranial temperature) for 15 mins, then
      kept in an awake state for 0.5, 3, 6, 18, 24, or 48 hrs before 2-hr MCAO; (ii)
      hyperthermia group (n = 8), which was subjected to 42 +/- 0.5 degrees C for 15
      mins, and then received the same treatment as the sham group; (iii) DPCPX (a
      selective central adenosine receptor antagonist)-treated control group, which was
      given the agent before normothermia pretreatment, then kept for a recovery time
      of 0.5 or 24 hrs (n = 8 in each group) before MCAO; (iv) DPCPX plus hyperthermia
      treated group, which was administered the agent at the same dose as the control
      before hyperthermic exposure, then selected for each recovery time (n = 8 in each
      group) before MCAO; (v) DPCPX-ischemic group, to which the agent was administered
      before MCAO (n = 8); and (vi) vehicle-ischemic group, in which peanut oil as a
      vehicle, instead of DPCPX, was injected before MCAO (n = 8). Values are expressed
      as mean +/- se. Statistical analysis was done by analysis of variance, followed
      by Scheffe's F test, Mann-Whitney U test, or the chi-square test as appropriate
      (p <.05). MAIN RESULTS: The infarcted volume in hyperthermic animals kept for 18
      or 24 hrs before the occlusion procedure was significantly smaller than in the
      sham controls, but not in rats kept for 0.5, 3.0, 6.0, and 48 hrs. DPCPX
      partially reversed the reduction in infarcted volume that was induced by
      hyperthermic preconditioning after focal ischemia, whereas the agent itself did
      not affect the volume after ischemia. CONCLUSION: These data indicate that
      hyperthermic pretreatment reduces the effects on MCAO-induced cerebral
      infarction, possibly via a partial mediation of the central adenosine receptors
      in the brain. The results also suggest a need for further studies to define the
      relationship between heat shock proteins and central adenosine receptors in
      preconditioning.

PMID- 12006814
TI  - Optimization of high-frequency oscillatory ventilation for the treatment of
      experimental pneumothorax.
AB  - OBJECTIVE: To determine the effect of frequency, amplitude, inspiratory time, and
      mean airway pressure on gas flow through a chest tube in an animal model of
      pneumothorax treated with high-frequency oscillatory ventilation (HFOV). DESIGN:
      Observational study. SETTING: Animal laboratory. SUBJECTS: Neonatal piglets (n =
      12). INTERVENTIONS: After saline lavage, a model of experimental pneumothorax was
      created by selective right mainstem intubation and manual ventilation at high
      peak inspiratory pressure. A chest tube was placed, and gas flow through the
      chest tube was measured with a pneumotachometer during HFOV with the SensorMedics
      3100A. The effects of frequency, inspiratory time, amplitude, and mean airway
      pressure on chest tube gas flow were determined. MEASUREMENTS AND MAIN RESULTS:
      Gas flow through the chest tube was significantly higher (p <.001) at 5 Hz (601
      +/- 23 mL/min) than at 10 Hz (464 +/- 64 mL/min) or 15 Hz (400 +/- 11 mL/min),
      while mean airway pressure, inspiratory time, and PaCO2 were kept constant. Gas
      flow was higher at an inspiratory time of 50% compared with one of 30% (645 +/-
      49 vs. 436 +/- 36 mL/min, respectively). Gas flow was directly related to
      amplitude (284 mL/min at an amplitude of 10 cm H2O, increasing to 877 mL/min at
      an amplitude of 80 cm H2O) when a 3.5-mm endotracheal tube was used; however, gas
      flow was attenuated at amplitudes of >40 cm H2O when smaller endotracheal tubes
      were used. Gas flow increased significantly with the increase of mean airway
      pressure from 92 mL/min at 15 cm H2O to 1433 mL/min at 30 cm H2O. CONCLUSIONS: In
      a neonatal piglet model of pneumothorax treated with HFOV, with amplitude
      adjusted to maintain constant alveolar ventilation, gas flow through the chest
      tube was significantly lower at 15 Hz compared with either 10 Hz or 5 Hz. Chest
      tube gas flow increased with increasing inspiratory time, amplitude, and mean
      airway pressure. These findings support the use of higher frequencies, short
      inspiratory times, low amplitudes, and low mean airway pressures for healing air
      leak with HFOV.

PMID- 12006815
TI  - Impaired subcortical and cortical sensory evoked potential pathways in septic
      patients.
AB  - OBJECTIVE: Sensory evoked potential (SEP) peak latencies were recorded in order
      to evaluate the incidence and severity of septic encephalopathy, testing the
      hypothesis that the occurrence of septic encephalopathy is more frequent than
      generally assumed. DESIGN: Prospective cohort study. SETTING: Medical intensive
      care unit of a university hospital. PATIENTS: Sixty-eight critically ill patients
      were studied within 48 hrs after the development of severe sepsis (n = 41) or
      septic shock (n = 27). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Septic
      encephalopathy was defined as prolongation of SEP peak latencies beyond the upper
      limit of the reference range of subcortical (N13-N20 interpeak latency) and
      cortical SEP pathways (N20-N70 interpeak latency), as well as asymmetry of peak
      latencies marked by the presence of subclinical cerebral focal signs. Subcortical
      SEP pathways were impaired in 34% and cortical SEP pathways in 84% of all
      patients. The prolongation of the cortical SEP pathway correlated with the Acute
      Physiology and Chronic Health Evaluation III score (r = 0.23; p <.0001). SEP peak
      latencies did not differ in patients with severe sepsis compared with those with
      septic shock. Subclinical cerebral focal signs were present in 24% of the
      subcortical SEP pathways and in 6% of the cortical SEP pathways. CONCLUSIONS:
      Septic encephalopathy occurs more frequently than generally assumed, and its
      severity is associated with the severity of illness. The impairment of
      subcortical and cortical SEP pathways was not different between patients with
      severe sepsis and those with septic shock.

PMID- 12006816
TI  - Early postoperative monocyte deactivation predicts systemic inflammation and
      prolonged stay in pediatric cardiac intensive care.
AB  - OBJECTIVE: Sepsis and systemic inflammatory response syndrome (SIRS) are major
      causes of morbidity and mortality after cardiopulmonary bypass. Attempts to
      suppress proinflammatory mediators have failed to improve outcomes in sepsis or
      in patients undergoing cardiopulmonary bypass. Recent work in adult patients has
      suggested that the balance between pro- and anti-inflammatory mediators is more
      important than the level of proinflammatory response alone. This balance may be
      reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with
      low concentrations indicating an excess of anti-inflammatory stimuli and relative
      immunodeficiency. We investigated the relationship between monocyte HLA-DR
      expression and the subsequent development of sepsis/SIRS in children undergoing
      cardiopulmonary bypass. DESIGN: A prospective, observational, clinical study.
      SETTING: A tertiary pediatric cardiac center. PATIENTS: Eighty-two infants and
      children undergoing elective cardiac surgery between March and December 1999.
      MEASUREMENTS AND MAIN RESULTS: Monocyte HLA-DR expression was assessed before and
      after surgery and was found to be related to the length of hospital stay and the
      development of complications including sepsis/SIRS. The inflammatory insult of
      cardiopulmonary bypass decreased monocyte HLA-DR expression in all children.
      Lowest concentrations were seen within 72 hrs of surgery and were significantly
      lower in cases that subsequently required prolonged intensive care support (p
      <.0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was
      associated with a greatly increased risk of later (minimum 4 days) development of
      sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was
      an independent predictor for the development of sepsis/SIRS after correction for
      age, bypass time, complexity of surgery, Paediatric Index of Mortality, and
      surgeon on multiple logistic regression analysis. CONCLUSIONS: Patients with
      decreased HLA-DR in the early postoperative period represent a subpopulation at
      greatly increased risk of later sepsis/SIRS. Such patients may benefit from
      strategies aimed to reduce this risk.

PMID- 12006817
TI  - Lessons from everyday lives: a moral justification for acute care research.
AB  - Progress in emergency and critical care requires that clinical research be
      performed on patients who are incapable of granting consent for research
      participation. Analyses of the ethics of such research have left some questions
      incompletely answered. Why should we be permitted to expose vulnerable patients
      to research risks without their consent? In particular, how do we justify
      research interventions that have no potential benefit for participants
      (nontherapeutic interventions)? This article presents a moral justification for
      nontherapeutic interventions in emergency research. By relying on a framework for
      assessing research risks, and by drawing on the example of pediatric research,
      this justification is founded in how institutional review boards, and society in
      general, analyze risk. Our justification for emergency research also suggests
      additional protections for emergency research participants, including a stringent
      threshold for research risk, that still permit important research to proceed.

PMID- 12006818
TI  - Survival of a 300-g infant ventilated by high-frequency oscillatory ventilation
      for respiratory distress syndrome.
AB  - We report a case of an infant delivered before the completion of 26 wks'
      gestation, weighing 300 g at birth, and treated with high-frequency oscillatory
      ventilation for respiratory distress syndrome. Her neurologic examination at 18
      months of age is compatible with mild delay in gross and fine motor skills.

PMID- 12006819
TI  - Cerebral and coronary gas embolism from the inhalation of pressurized helium.
AB  - OBJECTIVE: Inhalation of helium, which produces a change in the voice, is
      frequently used among young rock singers to improve their performance. DESIGN: A
      case report. SETTINGS: Adult medical intensive care unit in a university
      hospital. PATIENT: A 23-yr-old singer, who accidentally inhaled helium from a
      high pressurized tank without pressure reduction, presented with transient loss
      of consciousness and chest pain. INTERVENTIONS: Electrocardiogram, chest
      radiograph, biochemical and toxicological analyses, echocardiography, coronary
      angiography were performed. MEASUREMENTS AND MAIN RESULTS: At admission, the
      patient slowly regained consciousness. An electrocardiogram showed significant ST
      elevations in leads I, aVL, and V4-V6. The chest radiograph was consistent with
      pulmonary congestion and pneumomediastinum. The echocardiogram showed normal
      sized heart chambers with hypokinesis of the left ventricular lateral wall.
      Ethanol and urine cannabinoids were present in low concentrations, but no
      presence of opiates, methadone, cocaine, or amphetamines was documented. Troponin
      T was positive. Elevation of ST segments gradually disappeared within 30 mins,
      the drowsiness within 10 hrs, and the thoracic pain within 24 hrs. Coronary
      angiography showed normal coronary arteries. The patient was discharged on day 3
      without any symptoms and with normal electrocardiogram and chest radiograph.
      CONCLUSION: Accidental inhalation of helium under high pressure can cause
      symptomatic cerebral and coronary artery gas embolism.

PMID- 12006820
TI  - Vasopressin in piglet "pediatric models" of cardiac arrest.

PMID- 12006821
TI  - Optimized positive end-expiratory pressure--an elusive target.

PMID- 12006822
TI  - Mining for the genetic determinants of septic shock: when is it really gold?

PMID- 12006823
TI  - Development of novel, water-soluble inhibitors of poly (adenosine 5'-diphosphate
      ribose) synthetase activity for use in shock and ischemia-reperfusion injury.

PMID- 12006824
TI  - Transesophageal echocardiography in critically ill patients: what is the
      intensivist's role?

PMID- 12006825
TI  - New agents, new monitors, same unanswered questions.

PMID- 12006826
TI  - Interleukin-1 gene cluster polymorphisms: all in the family.

PMID- 12006827
TI  - Neutrophil migration and sepsis.

PMID- 12006828
TI  - Predicting significant vasospasm in patients with subarachnoid hemorrhage: a role
      for bedside microdialysis?

PMID- 12006829
TI  - Fish oil and endotoxemia.

PMID- 12006830
TI  - Protection from death in endotoxin shock: does fish oil need a LIF?

PMID- 12006831
TI  - Proton pump inhibitors and stress ulcer prophylaxis: pause for thought?

PMID- 12006832
TI  - Sepsis on the brain.

PMID- 12006833
TI  - Congenital heart disease, cardiopulmonary bypass, systemic inflammatory response
      syndrome, compensatory anti-inflammatory response syndrome, and outcome: evolving
      understanding of critical care inflammation immunology.

PMID- 12006834
TI  - Minimal risk: the debate goes on.

PMID- 12006835
TI  - A connection between the abdominal space and the mediastinum.

PMID- 12006836
TI  - The deleterious effect of heminic iron in transfused intensive care unit
      patients.

PMID- 12006838
TI  - Are we specializing in neglect?

PMID- 12006839
TI  - Recruiting minority nurses.

PMID- 12006843
TI  - Weekly dose of osteoporosis drug.

PMID- 12006845
TI  - Campaign finance reform.

PMID- 12006851
TI  - An overview of palliative nursing care.

PMID- 12006852
TI  - Thyroid Storm.

PMID- 12006853
TI  - Preoperative fasting: old habits die hard.
AB  - OVERVIEW: Prolonged preoperative fasting is a time-honored tradition. The typical
      order of "npo after midnight" (or no liquid or food after 12 am on the day of
      surgery) has been challenged in recent years-so much so that in 1999 the American
      Society of Anesthesiology (ASA) revised its practice guidelines for preoperative
      fasting in healthy patients undergoing elective procedures. The newer, more
      liberal recommendations, based on studies showing that pulmonary aspiration
      occurs only rarely as a complication of modern anesthesia, allow the consumption
      of clear liquids up to two hours before elective surgery, a light breakfast (tea
      and toast, for example) six hours before the procedure, and a heavier meal eight
      hours beforehand. There is a well-known lag between the dissemination and
      implementation of practice guidelines, so the authors sought to determine whether
      the publication of the revised ASA recommendations had changed preoperative
      fasting practices. They interviewed 155 patients in one hospital about their
      preoperative fasting, comparing instructed, actual, and ASA-recommended fasting
      durations for liquids and solids. Their findings demonstrate that the majority of
      patients continued to receive instructions of npo after midnight for both liquids
      and solids, whether they were scheduled for early or late surgery. On average,
      the patients fasted from liquids and solids for 12 and 14 hours, respectively,
      with some patients fasting as long as 20 hours from liquids and 37 hours from
      solids. These fasts were significantly longer than those recommended by the ASA,
      indicating that inappropriate preoperative fasting is an issue that demands
      attention. The authors conclude that more collaboration between nurses and
      physicians is needed to assure that fasting instructions are consistent with the
      ASA guidelines and that patients understand these directives.

PMID- 12006854
TI  - Families with chronically ill children.

PMID- 12006855
TI  - Nurse testimony in criminal court.

PMID- 12006856
TI  - What do credentials mean to you?

PMID- 12006857
TI  - Unacceptable pain levels.

PMID- 12006858
TI  - HIV-related fatigue.

PMID- 12006859
TI  - Nursing in Goma, Congo.

PMID- 12006860
TI  - The changing picture of hospital nurses.

PMID- 12006861
TI  - Screening for skin cancer: recommendations and rationale.

PMID- 12006863
TI  - American nurses receive international recognition. Nightingale Medal honors
      exemplary efforts.

PMID- 12006864
TI  - Hazardous drugs.

PMID- 12006866
TI  - Biventricular pacing.

PMID- 12006867
TI  - When seconds count, use an AED.

PMID- 12006868
TI  - Nebulized morphine for terminal dyspnea.

PMID- 12006869
TI  - Transfusion practices in critical care.

PMID- 12006870
TI  - Effects of cardiopulmonary bypass in children.

PMID- 12006872
TI  - Endocarditis in the immunocompromised.

PMID- 12006873
TI  - What comes around, goes around: a patient with septic embolus beats the odds.

PMID- 12006874
TI  - Neurogenic pulmonary edema.

PMID- 12006875
TI  - Surviving fulminant hepatic failure.

PMID- 12006876
TI  - You know you're an old nurse when...

PMID- 12006877
TI  - Family visitors-says who?

PMID- 12006878
TI  - Our first line of defense against bioterrorism part 2.
AB  - In March, Part 1 of this two-part series examined the challenges with identifying
      bioterrorism-specifically the anthrax outbreak. Part 2 explains what's being done
      to equip America's health care providers to recognize and respond to future
      attacks, while protecting the public.

PMID- 12006879
TI  - Let's get busy diversifying!

PMID- 12006882
TI  - Heighten your emergency preparedness.
AB  - Open and detailed communication is key to overcoming disasters and other
      emergencies.

PMID- 12006883
TI  - Stay in-the-know regarding informed consent.
AB  - Informed consent hinges on educating patients about their proposed treatments.

PMID- 12006884
TI  - Round out your department.
AB  - Clinical teaching rounds extend the staff orientation process without extending
      the budget.

PMID- 12006885
TI  - Taking HAART in the fight against HIV/AIDS.
AB  - Drug therapy for HIV/AIDS has come a long way since the 1980s when the focus was
      treating opportunistic infections that often accompany HIV. Today, caregivers
      target HIV itself with highly active (or highly aggressive) antiretroviral
      therapy (HAART) that interrupts viral replication.

PMID- 12006886
TI  - The safety needle switchover, part 1 of 2.
AB  - The relatively new Needlestick Safety and Prevention Act, which mandates
      implementing safer needle devices, is intended to create a safer health care work
      environment. Alabama's Children's Health System shares its strategy for
      compliance.

PMID- 12006887
TI  - The Synergy match-up.
AB  - Consider implementing the Synergy Model to optimize patient outcomes in your care
      setting.

PMID- 12006888
TI  - IC's boomerang: everything old is new again.
AB  - From whooping cough to bioterrorism, history repeats itself.

PMID- 12006889
TI  - How to plan for times of high patient census.

PMID- 12006890
TI  - Show your culturally sensitive side.

PMID- 12006891
TI  - Discontinue after last dose--an editorial and information about prescription
      writing.

PMID- 12006892
TI  - Clozapine use and risk of diabetes mellitus.
AB  - Recent reports have raised the concern that clozapine increases the risk for
      diabetes mellitus. Accurate pharmacoepidemiologic data on whether such a hazard
      exists and its magnitude are needed to enable clinicians and patients to make
      proper treatment decisions about clozapine. The authors performed a case-control
      study involving 7,227 cases of newly treated diabetes and 6,780 controls, all
      with psychiatric disorders. Cases and controls were older than 20 years and
      enrolled in government-sponsored drug benefit programs in New Jersey. The authors
      measured the use of clozapine or other antipsychotic medications and additional
      covariates. They developed logistic regression models adjusted for demographic,
      clinical, and health care use characteristics to identify whether clozapine users
      were at increased risk to begin treatment for diabetes. Clozapine use was not
      significantly associated with developing diabetes (adjusted odds ratio [OR],
      0.98; 95% confidence interval [CI], 0.74-1.31). There was no suggestion of
      relationships between larger dosages or longer durations of clozapine use and
      increasing risks of diabetes. On the other hand, nonclozapine antipsychotic
      medication use was associated with a modest but significantly increased risk of
      developing diabetes (adjusted OR, 1.13; 95% CI, 1.05-1.22). Among individual
      nonclozapine antipsychotics, significantly elevated risks were observed for two
      phenothiazine agents: chlorpromazine (adjusted OR, 1.31; 95% CI, 1.09-1.56) and
      perphenazine (adjusted OR, 1.34; 95% CI, 1.11- 1.62). In contrast to earlier
      reports, these results provide some reassurance that clozapine does not increase
      the risk of developing diabetes. Additional data from pharmacoepidemiologic
      studies and randomized controlled trials are needed to exclude the possibility of
      residual confounding and ensure the appropriate use of this agent.

PMID- 12006893
TI  - Antipsychotic-induced weight gain and therapeutic response: a differential
      association.
AB  - This study investigated the association between antipsychotic-induced weight gain
      and therapeutic response to haloperidol and three commonly used atypical
      neuroleptic medications in schizophrenia and schizoaffective disorder. The
      subjects were 151 patients enrolled in a double-blind experiment with a duration
      of 14 weeks comparing the therapeutic efficacy of haloperidol (n = 36), clozapine
      (n = 38), olanzapine (n = 38), and risperidone (n = 39). Absolute and relative
      (%) gain in body weight and body mass index (BMI) was determined for the entire
      duration of the double-blind treatment period; therapeutic response was assessed
      by the total score and the individual subscales of the Positive and Negative
      Symptom Scale. Compared with the pretreatment baseline, results indicated that
      for olanzapine and clozapine, therapeutic response was closely related to an
      absolute and relative gain in weight and to a gain in BMI. No association between
      weight gain and therapeutic response was found for risperidone and haloperidol.
      These findings suggest that patients who are likely to have the maximal benefits
      of olanzapine or clozapine treatment for symptom alleviation are at the highest
      risk of a clinically significant increase in weight gain.

PMID- 12006894
TI  - High serum creatinine kinase level: possible risk factor for neuroleptic
      malignant syndrome.
AB  - High creatinine kinase (CK) levels and leukocytosis are known to be associated
      with neuroleptic malignant syndrome (NMS). The authors sought to determine if
      their presence during non-NMS psychotic episodes is predictive of the later
      development of NMS. Sixteen psychotic inpatients who met the criteria for NMS
      were included. For statistical comparison, two control groups were formed by
      matching each study patient with two non-NMS patients for age, gender, ethnicity,
      and year and ward of hospitalization (n = 32). The maximal individual serum
      levels of CK, lactate dehydrogenase (LDH), serum glutamic oxaloacetic
      transaminase (SGOT), and white blood cell count (WBC) during all non-NMS
      psychotic episodes (Brief Psychiatric Rating Scale 40) were averaged. To
      normalize the distribution, the individual averages were transformed to natural
      logarithms (Ln). Mean Ln (average [CK]) in the patients with NMS was found to be
      6.46 +/- 0.91 IU/L, and in the non-NMS patients, 5.24 +/- 0.90 IU/L (actual serum
      CK levels, 911 +/- 747 IU/L and 343 +/- 620 IU/L, respectively). This difference
      was statistically significant (F [2,15] = 10.5, p < 0.0001). In addition, CK
      levels above the upper limit of normal were noted in 76% of psychotic episodes in
      the patients with NMS and in only 30% of psychotic episodes in the non-NMS
      patients (p < 0.0001). There was no significant difference between the NMS and
      non-NMS groups in Ln(LDH), Ln(SGOT), or Ln(WBC) (F [2,15] = 1.4, 2.1, and 0.9,
      respectively). The authors concluded that high serum CK level during non-NMS
      psychotic episodes seems to be a risk factor for future NMS. Therefore, CK
      measurement may be justified on admission of acutely psychotic patients who have
      other risk factors and a history of psychosis-associated CKemia.

PMID- 12006895
TI  - Fluoxetine in social phobia: a double-blind, placebo-controlled pilot study.
AB  - The objective of the study was to examine the efficacy of fluoxetine in social
      phobia. Sixty subjects were randomly assigned to 14 weeks of double-blind therapy
      with either fluoxetine or placebo. Dose was fixed at 20 mg for fluoxetine during
      the first 8 weeks of double-blind treatment; during the final 6 weeks, the dose
      could be increased every two weeks by 20 mg to a maximum of 60 mg/day. An
      intentto-treat analysis was used. A significant change from baseline to endpoint
      was found for both fluoxetine and placebo on the Liebowitz Social Anxiety Scale.
      However, no significant difference was found between fluoxetine and placebo. The
      change for fluoxetine was somewhat lower than that found with other selective
      serotonin reuptake inhibitors, whereas the placebo response was greater.
      Fluoxetine failed to separate from placebo in this trial. It is unknown whether a
      larger dose for longer duration would have yielded separation from placebo. A
      higher than usual placebo response rate was found.

PMID- 12006896
TI  - Fluoxetine alone in the treatment of first episode anxious-depression: an open
      clinical trial.
AB  - Many studies have reported the effectiveness of antidepressants in patients with
      so-called "anxious depression". This is the first report aimed at studying the
      beneficial therapeutic effects of fluoxetine alone on anxiety dimension in first
      episode drug naive patients suffering from DSM-IV major depression (MDD) and
      double depression (DD). Twenty-two outpatients (11 women and 11 men) were
      recruited in a University clinic for the treatment of a first episode pure MDD (n
      = 13) or DD (n = 9). All of the patients were drug naive, had Hamilton Rating
      Scale for Depression (HRSD) and Anxiety (HRSA) scores > or = 15, and were
      interviewed using the Structured Clinical Interview for DSM-IV-Patient edition.
      Fluoxetine alone (20 mg daily) was used in an attempt to treat depression with
      comorbid anxiety symptoms. A series of clinical- and self-rating scales (i.e.,
      HRSD, HRSA, Beck Depression Inventory, and Stait Trait Anxiety Inventory) were
      used to measure the psychopathology at day 0, and every 10 days until day 50. In
      the whole group, there were statistically significant changes, starting from the
      baseline, in depression and anxiety symptoms after 10 days of treatment. Self
      evaluated anxiety, however, improved after 20 days. Furthermore, at day 50, the
      patients with comorbid DD experienced a major improvement (diminished anxiety
      symptoms) compared to pure MDD patients. This open study suggests that depression
      and anxiety symptoms in first-episode drug-naive patients with anxious depression
      diminished very quickly with fluoxetine.

PMID- 12006897
TI  - Anxiety and depression symptoms and response to methylphenidate in children with
      attention-deficit hyperactivity disorder and tic disorder.
AB  - This study examined response to methylphenidate in children with attention
      deficit/hyperactivity disorder (ADHD) and chronic multiple tic disorder. The
      primary goal was to determine if children with anxiety or depression symptoms
      showed a less favorable response to treatment. Subjects were 38 prepubertal
      children who participated in an 8-week, double-blind, placebo-controlled,
      methylphenidate crossover evaluation. Treatment effects were assessed with direct
      observations of child behavior in public school and clinic settings; rating
      scales completed by parents, teachers, and clinicians; and laboratory analogue
      tasks. There was little evidence (group data) that children with anxiety or
      depression symptoms responded in a clinically different manner to methylphenidate
      than youngsters who did not exhibit these symptoms, particularly in school
      observations of the core features of ADHD. Seeming differences between children
      with and without comorbid anxiety or depression symptoms and drug response are
      likely explained by differences in pretreatment levels of negativistic behaviors
      (i.e., symptoms of oppositional defiant disorder or conduct disorder).
      Methylphenidate appears to be effective for the management of ADHD behaviors in
      children with mild to moderate anxiety or depression symptoms; nevertheless, much
      research remains to be performed in this area.

PMID- 12006898
TI  - Interactive model of therapeutic response in panic disorder: moclobemide, a case
      in point.
AB  - It was proposed that pre-post regression slopes be used to index treatment
      response when the effect of baseline scores differed among treatments
      (interaction between treatment and baseline score). Reanalyses of two studies
      using imipramine and fluoxetine in panic disorder showed doserelated decreases in
      pre-post slopes for the frequency of unexpected panic attacks, but not for the
      frequency of situational panic attacks or measures of agoraphobia. This report
      presents similar analyses of data from a study using moclobemide. Patients (N =
      452) with panic disorder were randomized to placebo or a fixed dose of
      moclobemide (75, 150, 300, 600, or 900 mg/day). They were treated double-blindly
      and evaluated at baseline and 1, 2, 3, 4, 6, and 8 weeks later. The authors
      analyzed the frequency of unexpected and situational panic attacks compiled from
      a daily diary, and fear and avoidance ratings based on the patient's main phobia
      using baseline (pre) and end-point (post) values for all randomized patients.
      Adjoining dose groups were combined. Both unexpected and situational panic
      attacks showed systematic doserelated suppression of pre-post treatment slopes.
      Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance
      differed reliably between treatment arms. This study replicates the authors'
      earlier findings, except for situational panic attacks, which probably were not
      reliably identified. Antidepressants selectively suppress panic attacks,
      especially unexpected attacks, but not agoraphobia. The findings are consistent
      with the hypothesis that panic disorder with agoraphobia has clinically separable
      biologic and cognitive components that respond differentially to treatment.
      Antidepressants benefit primarily patients with many unexpected panic attacks.
      Investigators should evaluate pre-post treatment slopes before comparing adjusted
      posttreatment means (analysis of covariance).

PMID- 12006899
TI  - Long-term benzodiazepine use and cognitive decline in the elderly: the
      Epidemiology of Vascular Aging Study.
AB  - Several cross-sectional studies have found cognitive impairment in subjects
      taking benzodiazepines for long periods. However, it is not known whether long
      term use of benzodiazepines accelerates cognitive decline in the elderly. The
      authors addressed this issue in a follow-up study of 1,389 people aged 60 to 70
      years recruited from the electoral rolls of the city of Nantes (Epidemiology of
      Vascular Aging study). Data on cognitive functioning (five cognitive tests),
      depressive symptoms (Center for Epidemiologic Studies-Depression Scale), anxiety
      symptoms (Spielberger Inventory Scale), use of psychotropics and other drugs, and
      tobacco and alcohol consumption were collected at baseline, 2-year, and 4-year
      examinations. People reporting to take benzodiazepines at one, two and three
      examinations were classified as episodic, recurrent, and chronic users,
      respectively. Among the 1,176 subjects (85%) who participated in the three
      examinations, the proportions of episodic, recurrent, and chronic users were 10%,
      6%, and 7%, respectively. Chronic users of benzodiazepines had a significantly
      higher risk of cognitive decline in the global cognitive test (Mini Mental State
      Examination) and the two attention tests than nonusers (Mini Mental State
      Examination: odds ratio [OR] [95% confidence interval (CI)] = 1.9 [1.0-3.5];
      Digit Symbol Substitution test: OR [95% CI] = 2.7 [1.6-4.7]; Trail Making test,
      part B: OR [95% CI] = 2.1 [1.2-3.7]). Overall, episodic and recurrent users had
      lower cognitive scores than nonusers, but differences were not statistically
      significant. These results were independent of age, sex, education, alcohol and
      tobacco use, anxiety and depression scores, and use of psychotropic drugs other
      than benzodiazepines. The findings suggest that long-term use of benzodiazepines
      is risk factor of increased cognitive decline in the elderly.

PMID- 12006900
TI  - Duration of imipramine therapy and relapse in panic disorder with agoraphobia.
AB  - It has been suggested that maintenance treatment of patients who have remitted
      panic disorder with agoraphobia beyond the six months of acute phase imipramine
      treatment may decrease the risk of relapse. This study further explores the
      relationship between relapse and duration of imipramine treatment in this
      population.Fifty-one patients, all in remission at the end of six months acute
      phase open trial with imipramine 2.25 mg/kg/day and randomized to double-blind
      maintenance or placebo substitution, discontinued imipramine treatment eventually
      and were followed over a 12-month risk period: 27 during first year placebo
      substitution, 7 after 12 months of imipramine maintenance in placebo
      substitution, and 17 after variable durations of imipramine maintenance in open
      discontinuation. There were no behaviorally oriented interventions or
      instructions at any time during the acute and maintenance phases of treatment or
      during imipramine discontinuation. Duration of imipramine treatment, the method
      of discontinuation (open versus placebo substitution), or any of the 9 variables
      from the demographic, clinical, and open treatment domains that were entered in a
      Cox proportional hazard model did not predict relapse. The rate of relapse after
      only 6 months of treatment (10 out of 27, 37%) was identical to the rate of
      relapse after 12 to 30 months of treatment (9 out of 24, 37.5%). The results
      suggest a lack of specific protective effects beyond prophylaxis and underscore
      the difficulty in predicting relapse in fully remitted panic disorder with
      agoraphobia patients. Early detection of relapse in patients who discontinue
      treatment may be a viable alternative to prediction.

PMID- 12006901
TI  - Antipanic drug modulation of 35% CO2 hyperreactivity and short-term treatment
      outcome.
AB  - Carbon dioxide (CO2) inhalation induces acute anxiety and panic attacks in
      patients with Panic Disorder (PD). Anti-panic drugs decrease CO2 reactivity after
      the first days of treatment; however, the clinical meaning of this finding has
      not yet been established. This study investigated the effects of treatment with
      tricyclic antidepressants and selective serotonin re-uptake inhibitors (SSRIs) on
      CO2 reactivity and compared the relationships between 35% CO2 hyperreactivity
      modulation and short-term clinical outcome. One hundred twenty-three patients
      with PD with or without agoraphobia who were hyperreactive to CO2 were randomly
      assigned to treatment groups with imipramine, clomipramine, paroxetine,
      sertraline, or fluvoxamine. A double-blind, randomized design was applied. Each
      patient received the 35% CO2 challenge on days 0, 7, and 30. The severity of
      clinical symptomatology was measured on days 0 and 30. Decreased hyperreactivity
      to 35% CO2 in all five treatment groups was already evident after the first week.
      The decrease in CO2 reactivity at the end of treatment was proportional to the
      degree of clinical improvement. Multiple regression analyses showed that the
      decrease in CO2 reactivity after the first week was a significant predictor for
      good clinical outcome after one month. The results of this study confirm evidence
      that psychoactive drugs effective in the treatment of PD decrease CO2
      hyperreactivity. They also suggest that precocious modulation of CO2 reactivity
      might fairly reliably predict short-term clinical outcome in patients with
      "respiratory" PD.

PMID- 12006902
TI  - Multivariate meta-analysis of controlled drug studies for obsessive-compulsive
      disorder.
AB  - Meta-analytic reviews of placebo-controlled studies for obsessive-compulsive
      disorder have found that clomipramine is more effective than drugs with more
      selective actions on serotonin reuptake, whereas in most direct comparisons,
      clomipramine's superiority has been less obvious. The authors used metaregression
      to identify sources of he-terogeneity in placebo-controlled trials of
      clomipramine, fluvoxamine, sertraline, and paroxetine. They evaluated such
      patient characteristics as age, gender, age of obsessive-compulsive disorder
      (OCD) onset, and baseline severity of OCD and depression, and such study
      characteristics as exclusion or inclusion criteria, length of single-blind
      prerandomization period, length of trial, number of subjects, and publication
      year. We found considerable heterogeneity across studies that was associated, in
      part, with publication year, length of single-blind prerandomization period,
      length of trial, and severity of patients' OCD. The apparent superiority of
      clomipramine persisted after controlling for these factors. The authors also
      confirmed previous reports that placebo response is higher in more recent
      studies. Meta-analyses can help characterize responders and nonresponders. The
      authors urge investigators to provide summaries of patient characteristics,
      especially baseline severity, age at onset, and duration of OCD, by patients'
      response.

PMID- 12006903
TI  - Effects of interrater reliability of psychopathologic assessment on power and
      sample size calculations in clinical trials.
AB  - Although rater training is increasingly used to improve the quality of the
      investigated outcome parameters, the reliability of assessments is not perfect.
      Thus, empirical reliability estimates should be used instead of theoretically
      assumed perfect reliability. Implications of the reliability of psychiatric
      assessments for sample size and power calculations in clinical trials are
      presented. The theoretical basis of sample size and power calculations using
      empirical reliability scores is delineated. Examples from contemporary research
      on schizophrenia and depression are used to illustrate several implications for
      study design and interpretation of results. The tremendous impact of the lack of
      reliability of psychopathologic assessments on sample size, power, and detectable
      true score differences in clinical trials is shown. The problem of multiple
      outcome variables with different reliabilities is addressed. Studies lacking
      power because of unreliable assessments carry the risk of false-negative findings
      and raise ethical questions. Rater training is strongly recommended to assess and
      improve interrater reliability whenever necessary and possible before trials are
      started. Sample size calculations and power analysis should be based on empirical
      reliability values of outcome parameters as part of quality assurance and cost
      savings.

PMID- 12006904
TI  - Treatment of codeine dependence with inhibitors of cytochrome P450 2D6.
AB  - Codeine is O-demethylated by cytochrome P450 2D6 (CYP2D6) to form the more potent
      drug morphine, accounting for much of codeine's analgesic and dependence
      producing properties. Because morphine production can be decreased by inhibition
      of CYP2D6, the authors hypothesized that CYP2D6 inhibition could be used to treat
      codeine dependence. A randomized, double-blind, placebo-controlled trial was
      conducted. All patients received brief behavioral therapy. Two weeks of baseline
      monitoring were followed by 8 weeks of daily treatment with fluoxetine or
      quinidine (two potent CYP2D6 inhibitors) or placebo. Thirty patients were
      assessed (all white, age 40 + 12 years using 127 + 79 mg/day of codeine [mean +
      SD]), and 17 entered treatment. Eight patients remained in the study by treatment
      week 8. Quinidine > fluoxetine > placebo inhibited CYP2D6 as reflected in the
      change of the O-demethylation of dextromethorphan, a specific CYP2D6 probe. At
      treatment week 8, placebo, quinidine, and fluoxetine reduced mean daily codeine
      intake by 57%, 56%, and 51% of baseline intake respectively; there was no
      difference among treatment groups. In this small sample, CYP2D6 inhibitors did
      not appear to have a useful role in the treatment of codeine dependence.

PMID- 12006905
TI  - Designer drugs that are potent inhibitors of CYP2D6.
AB  - Some abused drugs are substrates of CYP2D6 (e.g., paramethoxyamphetamine,
      methylenedioxy-methamphetamine). CYP2D6 inhibition by concurrently used drugs of
      abuse could potentiate such drugs and increase acute toxicity. Ten designer drugs
      were tested as inhibitors of CYP2D6. Only 1-methyl-4-phenyl-4
      propionoxypiperidine (MPPP) and 1-[2-phenylethyl]-4-phenyl-4-acetoxypiperidine
      (PEPAP) interacted significantly (Ki 1.6 microM and 0.3 microM, respectively).
      Both are synthetic analogues of meperidine sold as "synthetic heroin." No CYP2D6
      mediated metabolites were detected for either compound. Concurrent oral use of
      CYP2D6 substrates with MPPP and PEPAP may represent a kinetic drug interaction
      risk, but this risk must be confirmed clinically.

PMID- 12006906
TI  - Effect of olanzapine on glutamate levels in cerebrospinal fluid of patients with
      schizophrenia.

PMID- 12006907
TI  - Effectiveness of serotonin (5-HT)1A receptor agonist in a patient with
      psychogenic apneusis.

PMID- 12006908
TI  - Prolonged coma caused by low sodium and hypo-osmolarity during treatment with
      citalopram.

PMID- 12006909
TI  - Toxic serotonin syndrome successfully treated with electroconvulsive therapy.

PMID- 12006910
TI  - Does topiramate elevate serum lithium levels?

PMID- 12006911
TI  - Are gender differences in antiobsessional response related to different
      clomipramine metabolism?

PMID- 12006913
TI  - Do lipids, blood pressure, diabetes, and smoking confer equal risk of myocardial
      infarction in women as in men? The Reykjavik Study.
AB  - BACKGROUND: Studies on coronary risk factors in men and women are mainly based on
      mortality data and few compare results of both sexes with consistent study design
      and diagnostic criteria. This study assesses the major risk factors for coronary
      events in men and women from the Reykjavik Study. DESIGN: Within a prospective,
      population-based cohort study individuals without history of myocardial
      infarction were identified and the relative risk of baseline variables was
      assessed in relation to verified myocardial infarction or coronary death during
      follow-up. METHODS: Of the 9681 women and 8888 men who attended risk assessment
      from 1967-1991, with follow-up period of up to 28 years, 706 women and 1700 men
      suffered a non-fatal myocardial infarction or coronary death. RESULTS: Serum
      cholesterol was a significant risk factor for both sexes, with hazard ratios (HR)
      decreasing with age. Systolic blood pressure was a stronger risk factor for women
      as was ECG-confirmed left ventricular hypertrophy (women HR 2.89, 95% confidence
      interval [CI] 1.67-5.01; men HR 1.11 [CI 0.86-1.43]). Fasting blood glucose > or
      =6.7 mmol/L identified significantly higher risk for women (HR 2.65) than men (HR
      2.08) as did self-reported diabetes. Triglyceride risk was significantly higher
      for women and decreased significantly with age. Smoking increased risk two- to
      five-fold, increasing with dose, for women, which was significantly higher than
      the doubling in risk for men. CONCLUSIONS: This large study of the major risk
      factors compared between the sexes demonstrates similar relative risk of
      myocardial infarction associated with cholesterol for both sexes, however, the
      relative risk is higher in women for many other risk factors such as smoking,
      diabetes, elevated triglycerides and left ventricular hypertrophy.

PMID- 12006914
TI  - Is carotid artery intima-media thickening a reliable marker of early
      atherosclerosis?
AB  - BACKGROUND: It is widely believed that carotid artery intima-media thickening
      represents an early marker for the development of atheroma. However, carotid
      intima-media thickening might also be expected to occur in response to an
      increased tensile stress and decreased wall shear stress which may accompany
      physical exercise. DESIGN, METHODS, AND RESULTS: In order to test this hypothesis
      24 athletes (professional footballers) were compared to 14 age and sex matched
      control subjects. Each subject underwent carotid and femoral ultrasonography and
      echocardiography. The athletes had a greater left ventricular mass index compared
      with the controls: 135 (127-143) vs. 104 (91-116) g/m2, p < 0.001. In addition,
      they had a greater carotid intima-media thickness (IMT): 0.55 (0.52-0.57) vs.
      0.51 (0.48-0.54) mm, p < 0.05. However, carotid artery diameters, femoral IMT and
      femoral artery diameters were similar: 6.0 (5.9-6.2) vs. 5.8 (5.6-6.1) mm, 0.43
      (0.42-0.45) vs. 0.43 (0.41-0.45) mm and 8.3 (8.0-8.6) vs. 8.4 (8.0-8.7) mm,
      respectively. CONCLUSIONS: The increased carotid IMT of the athletes may result
      from intermittent exposure to markedly elevated systemic arterial pressures
      during exercise, resulting in intermittent elevations in carotid wall tensile
      stress. The lack of a disparity between athletes and controls for femoral IMT may
      be explained by the intermittent elevation of femoral wall tensile stress being
      accompanied by increased femoral artery blood flow and wall shear stress, which
      would tend to reduce any wall thickening. This is an important observation, since
      it suggests that an increased carotid IMT cannot be relied on solely as a marker
      of early atherosclerosis.

PMID- 12006915
TI  - Lipid modulation and liver function tests. A report of the Program on the
      Surgical Control of the Hyperlipidemias (POSCH).
AB  - BACKGROUND: Statin drugs are known to cause dose-dependent abnormalities in liver
      function tests (LFTs), with elevations three times the upper limits of normal of
      the aminotransferase enzymes in up to 2.5% of patients on the highest
      prescribable doses. The Program on the Surgical Control of the Hyperlipidemias
      (POSCH) trial employed no hypocholesterolaemic drugs and used a surgical
      procedure, partial ileal bypass, as the intervention modality. METHODS: Serum
      total bilirubin, alkaline phosphatase and serum glutamic-oxaloacetic transaminase
      (SGOT) (equivalent to aspartate aminotransferase [AST]), were the LFTs obtained
      in POSCH at baseline, 3 months, annually for 5 years, and at 7 or 10 years
      postrandomization. RESULTS: Abnormal values were found for total bilirubin in
      seven of 416 control group (CG) patients (1.68%) and in 34 of 373 intervention
      group (IG) patients (9.16%) (P = 0.001); for alkaline phosphatase, in 28 of 378
      (7.41%) and in 41 of 326 (12.58%) (P = 0.0214); and for SGOT, in 102 of 412
      (24.76%) and in 161 of 372 (43.28%) (P = 0.001). Values twice the upper limit of
      normal occurred in 1 CG and 1 IG patient for total bilirubin and for alkaline
      phosphatase, and in 11 CG and 7 IG patients for SGOT (NS). Values three times the
      upper limit of normal did not occur in any patient for total bilirubin or
      alkaline phosphatase, and occurred in 3 CG and 5 IG patients for SGOT (NS).
      CONCLUSIONS: In POSCH, the IG demonstrated statistically significant mild
      increases for total bilirubin, alkaline phosphatase and SGOT levels, with no
      significant increases in values twice or greater the upper limits of normal.

PMID- 12006916
TI  - Declaring war on undertreatment: rationale for an aggressive approach to lowering
      cholesterol.
AB  - Few things are better understood within the medical community than the
      relationship between elevated total and low-density lipoprotein cholesterol (LDL
      C) levels, cardiovascular disease and death. There is consensus in the treatment
      guidelines of numerous national and international bodies that cholesterol levels
      in at-risk patients should be reduced to target levels that have been shown in
      population studies to be associated with low rates of coronary heart disease
      (CHD). However, dyslipidaemia continues to be underdiagnosed and undertreated.
      The 'landmark' statin trials have demonstrated unequivocally that effective lipid
      lowering therapy significantly decreases CHD morbidity and mortality.
      Furthermore, these benefits of lipid-lowering therapy are not limited to middle
      aged men, but extend across a broad range of patient populations. Recent trial
      data suggest that lowering LDL-C to target levels is possible in a substantial
      proportion of patients when statins are administered aggressively and results in
      a greater reduction in the risk of major coronary events. This reduction in
      events is seen in patients with stable coronary disease as well as those treated
      immediately after an acute coronary syndrome. Although strong clinical and
      angiographic evidence shows that intensive treatment prevents morbidity and saves
      lives, indications are that clinicians are still waiting too long to treat
      dyslipidaemia and when treatment is initiated it is often at inadequate dosages.
      Undertreatment of dyslipidaemia is an issue that the healthcare community can no
      longer ignore.

PMID- 12006917
TI  - C-reactive protein and carotid intimal medial thickness in a community
      population.
AB  - BACKGROUND: C-reactive protein (CRP) has been linked to cardiovascular disease
      and atherosclerosis. Large-scale epidemiological studies have shown a correlation
      of CRP level with risk of stroke, myocardial infarction and peripheral arterial
      disease. Nevertheless, the question whether serum CRP itself is an independent
      indicator of the atherosclerotic process remains unanswered. METHODS: In a
      community-based sample free of advanced atherosclerotic disease (n = 1018; mean
      age +/- SD, 54.1 +/- 12.0 years; 49.7% women) we examined the relationship
      between carotid intimal medial thickness (IMT), conventional vascular risk
      factors (that is, smoking, obesity, elevated blood pressure, diabetes mellitus,
      hypercholesterolaemia) and serum CRP. RESULTS: We found an association between
      increasing IMT values with increasing CRP values for all sites within the carotid
      system (for example, common carotid artery [CCA-] IMT, beta = 0.174, P < 0.001).
      The relationship was weakened after accounting for the above-mentioned
      conventional risk factors (linear regression), particularly body mass index, but
      remained significant (for example, mean CCA-IMT beta = 0.02, P = 0.042).
      Including fibrinogen in the regression made the relationship no longer
      significant (mean CCA-IMT beta = 0.01, P = 0.277). CONCLUSION: It is unlikely
      that CRP per se is a major independent cause of early arteriosclerosis.
      Elevations of CRP, or less specifically chronic inflammation, may mediate the
      effect of certain conventional risk factors on promoting atherogenesis,
      especially obesity.

PMID- 12006918
TI  - Hepatic lipase gene -514 C/T polymorphism and premature coronary heart disease.
AB  - BACKGROUND: A common polymorphism in the hepatic lipase (HL) gene promoter, 
      514C/T, affecting enzyme activity, has been associated with alterations in plasma
      lipoprotein levels. However a relationship with coronary heart disease (CHD) is
      less well documented. DESIGN AND METHODS: We studied HL -514 C/T in 562 Caucasian
      CHD patients aged under 50 years and in 642 Caucasian community recruited
      subjects without historical evidence of CHD. RESULTS: Male CHD subjects (n = 490)
      had a 41% carrier rate for the C to T substitution, compared with 33% in
      corresponding controls (n = 330), [OR = 1.42 (95% CI:1.06-1.90), P < 0.02], T
      allele frequencies being 0.231 and 0.177 respectively [OR = 1.39 (1.08-1.78), P <
      0.01]. In male CHD subjects, the T allele was associated with higher HDL
      cholesterol (HDL-C) (CC: 0.95 +/- 0.24 (SD); CT: 1.04 +/- 0.41; TT: 1.01 +/- 0.20
      mmol/l, P = 0.02, ANOVA) but the trend was not significant in females. In male
      CHD patients the T allele was more frequently encountered in those with high (>
      4.5 mmol/l) than in those with low triglycerides [68% vs. 39%, OR = 3.13 (1.54
      6.67), P = 0.001]. In community control subjects, the T allele was associated
      with a trend to higher HDL-C levels, the significance varying between subgroups
      while, in males, serum total and LDL-cholesterol were significantly lower in T
      homozygotes than in the other two genotypes (LDL-C: 2.73 +/- 0.63 vs. 3.56 +/-
      0.95 mmol/l; P = 0.01). During the course of this study, a previously unreported
      promoter region polymorphism was found exclusively on -514C chromosomes (-592A/G,
      A allele frequency 0.108, 95% CI 0.09 - 0.126). It can lead to mistyping of C as
      T alleles in C/T heterozygotes, resulting in overestimation of -514 T
      homozygotes. CONCLUSIONS: The T allele of the hepatic lipase -514 C/T
      polymorphism is associated with changes in plasma lipids. The superficially
      paradoxical predisposition to CHD in males is attributable to impairment of TG
      rich lipoprotein metabolism and reverse cholesterol transport.

PMID- 12006919
TI  - Diagnosis of acute myocardial ischaemia using probabilistic methods.
AB  - BACKGROUND: The present study was undertaken to test the effectiveness of an
      established equation for estimating the probability of acute cardiac ischaemia,
      but in an environment different from that in which it was developed. METHODS AND
      RESULTS: A total of 255 patients who presented to the accident and emergency
      department of Glasgow Royal Infirmary with symptoms suggesting acute ischaemic
      heart disease were enrolled in the study. Their clinical data and ECG
      measurements were used as input to the Time-Insensitive Predictive Instrument
      (TIPI) equation to calculate the probability of acute myocardial ischaemia being
      present. Receiver operating characteristic (ROC) curves were derived to evaluate
      the usefulness of the equation in diagnosing acute myocardial infarction versus
      nonmyocardial infarction and acute cardiac ischaemia verses nonischaemic chest
      pain. For the diagnosis of acute cardiac ischaemia versus noncardiac chest pain,
      the area under the ROC curve was 0.61 (95% CI 0.55-0.67). For the diagnosis of
      acute myocardial infarction versus nonmyocardial infarction, there was increased
      performance with the area under the ROC curve being 0.71 (95% CI 0.65-0.76). This
      compares with the originally published findings of a value of 0.88 for the area
      under the curve for the diagnosis of acute myocardial ischaemia versus noncardiac
      chest pain. CONCLUSION: The study suggests that equations for the diagnosis of
      acute cardiac ischaemia developed in one centre may not readily translate
      elsewhere, possibly due to varying interpretations of the clinical and ECG
      criteria used.

PMID- 12006920
TI  - Value of home blood pressures as predictor of target organ damage in mild
      arterial hypertension.
AB  - BACKGROUND: Home blood pressure measurement has gained increasing importance for
      the management of hypertensive patients. The aim of our study was to compare
      levels of clinic (CBP), ambulatory (ABP), and home blood pressure (HBP)
      measurements, and their relationships with various indexes of target organ damage
      in I-II grade essential hypertension. DESIGN AND METHODS: Thirty-eight essential
      hypertensives underwent evaluation of clinic, ambulatory and home blood
      pressures. Each patient recorded HBP for 2 days with a digital BP monitor three
      times daily, the first time on the same day during which ABP monitoring was
      simultaneously performed. Moreover, in all subjects electrocardiogram recording,
      echocardiographic study, microalbuminuria assay and fundus oculi examination were
      obtained. RESULTS: The average HBPs obtained on the first day, in particular
      systolic values, were quite similar to mean daytime ambulatory BP recorded on the
      same day. Clinic BP, both systolic and diastolic, showed no significant
      correlation with left ventricular mass index (LVMI) and with albumin excretion
      rate (AER), whereas a correlation barely significant was observed with an index
      of global target organ damage (GTODi), including cardiac, renal and retinal
      parameters. On the contrary, home blood pressures, especially those recorded on
      the second day, correlated significantly, and more tightly than clinic BP, with
      LVMI, AER and GTODi. CONCLUSIONS: Our study seems to justify the adoption of home
      BP monitoring in the management of hypertensive patients, as a useful complement
      to clinical readings, and may provide additional prognostic information.

PMID- 12006921
TI  - The association of PAI-1 promoter 4G/5G insertion/deletion polymorphism with
      myocardial infarction and stroke in young women.
AB  - BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G
      insertion/deletion polymorphism has been associated with increased risk of
      myocardial infarction (MI) and decreased risk of cerebrovascular events. Whether
      these results apply to young women is not known. METHODS: We genotyped 78 MI
      cases, 106 stroke cases and 385 age-matched controls from a population-based case
      control study of MI and stroke in women < 45 years old. RESULTS: The risk of MI
      was significantly decreased in carriers of the 4G allele compared with 5G/5G
      homozygotes, and the association persisted upon adjustment for other risk factors
      (age- and race-adjusted OR 0.50, 95% CI 0.29-0.85). Carrying the 4G allele was
      not associated with stroke, either overall or according to subtype. The
      association of this polymorphism with MI or stroke did not vary significantly by
      presence or absence of established cardiovascular risk factors, assessed on
      either an additive or multiplicative scale. CONCLUSIONS: These data suggest a
      decreased risk of MI among young women carrying the 4G allele of the PAI-1 4G/5G
      polymorphism. Although this result contrasts with those of previous studies of
      older adults and young men, it may highlight the influence of genetic factors on
      the development of MI within the context of particular hormonal or environmental
      influences.

PMID- 12006922
TI  - Reporting randomized, controlled trials: where quality of reporting may be
      improved.
AB  - INTRODUCTION: Evidence-based medicine relies on reproducible, high-quality
      reporting in the literature. Previous evaluations, which have assessed 11 basic
      elements of design and analysis in top impact clinical journals (both nonsurgical
      and surgical), have demonstrated that the reporting quality is less than perfect,
      although improving. The current study evaluates the quality of reporting in
      Diseases of the Colon and Rectum and other clinically related journals to
      identify specific areas where future improvements may be made. METHODS: Two
      independent evaluators assessed all randomized, controlled trials published in
      Diseases of the Colon and Rectum in the years 1990, 1995, and 2000. Additional
      assessments for 2000 were performed on all randomized, controlled trials
      published in Annals of Surgery, Archives of Surgery, and Gastroenterology. The
      frequency of reporting of 11 explicitly defined, traditionally important, basic
      elements of design and analysis were determined. These elements included
      reporting of eligibility criteria, admission before allocation, randomization
      (and method), blinded assessment (patient and observer), complications, loss to
      follow-up, statistical approach and tests, and power calculation. RESULTS:
      Interobserver reliability was strong (kappa, 0.76). The number of randomized,
      controlled trials published in Diseases of the Colon and Rectum increased from 5
      (in 1990) to 13 (in 1995) to 17 (in 2000). Of the 1990 randomized, controlled
      trials, an average of 60 percent of the 11 basic elements were reported. Of the
      1995 randomized, controlled trials, 72 percent of the items were reported (P =
      0.05), whereas of the 2000 randomized, controlled trials, 77 percent of the 11
      items were reported (P < 0.002 vs. 1990). The best-reported items were
      eligibility criteria, discussion of statistical tests, and accounting for all
      patients lost to follow-up. Only 11 percent of the 2000 randomized, controlled
      trials reported statistical power calculations. For the other journals that were
      evaluated, 72 to 88 percent of items were reported, with eligibility criterion
      being the best consistently reported item and power calculation being the worst.
      CONCLUSIONS: For Diseases of the Colon and Rectum, the number of randomized,
      controlled trials and the quality of reporting is improving. However, although
      certain research standards are reported adequately, others are not. The
      calculation of statistical power is clearly important when interpreting
      randomized, controlled trial results (whether differences are reported or not),
      yet only 11 percent of studies contained this information. Improving the
      reporting of this single item would likely lead to improving the overall quality
      of clinical studies in colorectal surgery. Improved reporting might be best
      facilitated by having authors adhere to a list of explicitly determined elements
      that should be included.

PMID- 12006923
TI  - Mucosal assessment for dysplasia and cancer in the ileal pouch mucosa in patients
      operated on for ulcerative colitis--a 30-year follow-up study.
AB  - PURPOSE: Sporadic reports of epithelial dysplasia and the occasional development
      of adenocarcinoma in the ileal pouch mucosa have recently appeared in the
      literature, pointing toward yet another long-term complication of the continent
      ileostomy and the pelvic pouch. The incidence of dysplasia and the risk for
      developing cancer has not been critically evaluated, however, and the reports are
      contradictory, with most having short observation times. The purpose of this
      study was to report long-term mucosal adaptation patterns and the incidence of
      dysplasia in Kock pouches after a mean follow-up of 30 years for patients
      previously operated on for ulcerative proctocolitis. METHODS: Two sets of two
      pathologists each (in Gothenburg, Sweden, and Manchester, United Kingdom)
      examined sequential, small-intestinal biopsy specimens from 40 patients with Kock
      pouch to observe long-term epithelial changes, with particular reference to the
      presence of dysplasia. RESULTS: There was full agreement between the two groups
      regarding the absence of high-grade dysplasia and invasive carcinoma (Categories
      4 and 5 of the Vienna classification). There was, however, significant
      disagreement in reporting the frequency of low-grade and indefinite categories of
      dysplasia (Categories 2 and 3, of the Vienna classification). No attempt was made
      to report the differences within each set of pathologists. CONCLUSION: Because no
      case of high-grade dysplasia or invasive carcinoma was found in this study after
      a mean follow-up of 30 years, we conclude that it is very unlikely for invasive
      carcinoma to be a complication in ileal pouch mucosa.

PMID- 12006924
TI  - Surgical treatment of high-grade anal squamous intraepithelial lesions: a
      prospective study.
AB  - PURPOSE: The prevalence of anal squamous intraepithelial lesions is high among
      human immunodeficiency virus-positive homosexual males and, to a lesser extent,
      among human immunodeficiency virus-negative homosexual males. Furthermore, the
      incidence of high-grade squamous intraepithelial lesions, the putative precursor
      lesion to invasive cancer, is also high. We report the first prospective study of
      high-resolution anoscopy-directed surgical treatment of high-grade squamous
      intraepithelial lesions. METHODS: A prospective study of patients undergoing
      surgical treatment of high-grade squamous intraepithelial lesions
      (excision/cauterization of lesions visualized with high-resolution anoscopy) was
      performed. Follow-up anoscopy with biopsy and Papanicolaou smear was performed
      every three to six months. RESULTS: Patients diagnosed with high-grade squamous
      intraepithelial lesions during the course of their participation in a prospective
      cohort study of anal squamous intraepithelial lesions were identified. From this
      group, 37 patients who were treated surgically between 1995 and 1999 were
      studied. Of these, 29 had tested positive for human immunodeficiency virus and 8
      were negative for the virus. Mean patient age was 45 +/- 8 years. Mean duration
      of follow-up was 32.3 +/- 20.6 months in the human immunodeficiency virus
      negative group and 28.6 +/- 12.9 months in the human immunodeficiency virus
      positive group. No human immunodeficiency virus-negative patient developed
      recurrent high-grade squamous intraepithelial lesions. Twenty-three of 29 human
      immunodeficiency virus-positive patients had persistent or recurrent high-grade
      squamous intraepithelial lesions (P = 0.003; mean time to recurrence, 12 months).
      Six patients underwent reoperation for high-grade squamous intraepithelial
      lesions (4 recurred by 6 months). No patients developed incontinence, stenosis,
      postoperative infection, or significant bleeding after surgical treatment.
      CONCLUSIONS: Surgical intervention directed by high-resolution anoscopy is safe
      and eliminates high-grade squamous intraepithelial lesions in human
      immunodeficiency virus-negative patients. The high persistence or recurrence rate
      in human immunodeficiency virus-positive patients suggests that multiple staged
      procedures and continued surveillance may be necessary.

PMID- 12006925
TI  - Evaluation of toxicity and quality of life using a diary card during
      postoperative radiotherapy for rectal cancer.
AB  - PURPOSE: Adjuvant pelvic radiotherapy after radical surgery for rectal cancer may
      produce several side-effects (mainly gastrointestinal) capable of affecting
      patient lifestyle. This prospective study evaluated by means of a diary card the
      toxicity and daily changes in the quality of life of patients with rectal cancer
      treated with postoperative pelvic radiotherapy. METHODS: We used a diary card
      listing ten items about lifestyle changes and side-effects compiled by patients
      themselves. The patients were stratified by age (< or = 65 vs. > 65 years), the
      presence or not of a stoma, and the administration or not of concurrent
      chemotherapy. RESULTS: Twenty-seven patients were evaluable. The mean number of
      bowel movements increased across time, without statistically significant
      differences. Nausea and appetite did not significantly change during the
      treatment period. There was a statistically significant, progressive increase in
      the perception of pain (P < 0.03). Although not significantly, the anxiety scores
      were lower during radiotherapy than at baseline. Daily activities and compliance
      with therapy did not significantly change during the treatment. There was a
      significant worsening in overall well-being (P < 0.04) and quality of life
      evaluation (P < 0.03). The patients who received chemoradiotherapy experienced a
      worsened lifestyle and greater side-effects. Older patients experienced less pain
      but had statistically significant higher levels of anxiety. Patients with a stoma
      reported a better quality of life score than those without. CONCLUSIONS: The use
      of a diary card may be an adequate means of detecting the extent of treatment
      related changes in the lifestyle of patients with rectal cancer treated by
      postoperative radiotherapy.

PMID- 12006927
TI  - Results of aggressive resection of lung metastases from colorectal carcinoma
      detected by intensive follow-up.
AB  - PURPOSE: Although outcome of resection for colorectal carcinoma has improved,
      about 30 percent of patients develop metastatic lesions. Small pulmonary
      metastases 1 cm or less in diameter now can be detected by diagnostic tests
      including chest radiography and computed tomography. We evaluated results of our
      strategy for intensive follow-up after resection of colorectal cancer and
      aggressive resection of lung metastases disclosed by these periodic examinations.
      METHODS: Our follow-up program for lung metastasis includes a serum
      carcinoembryonic antigen assay every two months and chest radiography every six
      months. Surgical resection of lung metastases was performed if the primary and
      any nonpulmonary metastases had been controlled, lung metastases numbered four or
      fewer, and pulmonary functional reserve was adequate. Standard operation for lung
      metastasis was lobectomy, and lymph node dissection was added in cases of tumor
      size over 3 cm. Forty-two patients underwent 50 lung resections for metastatic
      colorectal cancer between 1992 and 1999. Long-term survival was assessed in terms
      of clinical variables. RESULTS: Overall five-year survival rate after resection
      of lung metastases from colorectal cancer was 63.7 percent. Variables
      significantly affecting postthoracotomy survival were primary tumor histology,
      number of nodules, and disease-free interval up to appearance of the lung
      metastases, and primary tumor histology was an independent prognostic factor.
      CONCLUSION: Intensive follow-up for lung metastases after resection of colorectal
      cancer and aggressive resection improved postoperative survival rate. Patients
      with well-differentiated adenocarcinoma of primary tumor, a solitary metastatic
      nodule, and disease-free interval of at least two years after initial surgery are
      likely to be long-term survivors.

PMID- 12006929
TI  - Accuracy of investigations for asymptomatic colorectal liver metastases.
AB  - PURPOSE: The aim of this study was to prospectively assess the accuracy of the
      most promising imaging and tumor marker tests in liver metastasis diagnosis on
      follow-up of asymptomatic colorectal cancer patients during a median of 57 months
      after primary tumor resection. METHODS: One hundred patients, who were considered
      free of liver metastases after primary colorectal cancer resection and
      conventional follow-up, were screened for liver metastases by computerized
      tomography, magnetic resonance and ultrasound scans, ultrasound Doppler and
      isotope assessment of changes in hepatic arterial and portal venous flow, and
      serum estimation of carcinoembryonic antigen. Patients were followed up during a
      median of 41 months to identify those who developed liver metastases. RESULTS:
      The most sensitive technique was computerized tomography (sensitivity 0.67,
      specificity 0.91). Computerized tomography and magnetic resonance but not
      ultrasound were 100 percent accurate in differentiating liver metastases from
      other hepatic lesions. Techniques based on changes in hepatic arterial and portal
      venous flow had lower diagnostic accuracies (Doppler perfusion index, sensitivity
      0.58, specificity 0.57; hepatic perfusion index, sensitivity 0.50, specificity
      0.55), whereas ultrasound scanning identified only 43 percent (sensitivity 0.43,
      specificity 0.96) and serum carcinoembryonic antigen 33 percent (sensitivity
      0.33, specificity 0.81) of patients with asymptomatic liver metastasis.
      Sensitivity could be improved by using tests in combination but this reduced
      specificity. CONCLUSIONS: Computerized tomography was the most sensitive test for
      asymptomatic colorectal liver metastases, but only 67 percent of affected
      patients were identified.

PMID- 12006930
TI  - Cost structure of laparoscopic and open sigmoid colectomy for diverticular
      disease: similarities and differences.
AB  - PURPOSE: Although laparoscopic colectomy has demonstrated a variety of
      advantages, it remains unclear whether the reductions in length of stay and
      faster return of bowel function will offset potential increases in cost caused by
      operating time and instrumentation. The purpose of this study was to compare the
      direct cost structure of elective open and laparoscopic resection for sigmoid
      diverticulitis. METHODS: We compared consecutive elective open and laparoscopic
      sigmoid colectomies (n = 71 and n = 61, respectively) performed from March 1,
      1999, through December 31, 2000. Data collected included age, gender, body mass
      index, American Society of Anesthesia score, indication for surgery, morbidity,
      mortality, conversion (laparoscopic only), operating time, and length of hospital
      stay. Direct cost data were provided by Stanford's integrated hospital cost
      management and decision software. Indirect costs and total costs were not
      addressed. Data were analyzed by Student's t-test and chi-squared test where
      appropriate. Significance was set at P < 0.05. All data are presented as mean +/-
      standard error of the mean. RESULTS: There were 132 elective sigmoid colectomies
      for diverticular disease (61 laparoscopic and 71 open procedures). There were no
      significant differences between the groups with respect to age, male/female
      ratio, or body mass index. Operating time was similar (109 +/- 7 minutes for
      laparoscopic procedures vs. 101 +/- 7 minutes for open procedures). The
      laparoscopic group had a significantly shorter length of stay (3.1 +/- 0.2 vs.
      6.8 +/- 0.4 days), fewer pulmonary complications (1 (1.6 percent) vs. 4 (5.6
      percent)) and fewer wound infections (0 vs. 5 (7 percent)). Conversion to open
      colectomy was required in 4 (6.6 percent) of 61 patients. Readmission occurred in
      three laparoscopic colectomy patients (4.9 percent) and four open colectomy
      patients (5.6 percent). There was one operative death in the laparoscopic group
      (1.6 percent) and no deaths in the open group. Total direct cost per case was
      significantly less for laparoscopic procedures ($3,458 +/- 437) than for open
      colectomies ($4321 +/- 501; P < 0.05, Student's t-test), and operating costs were
      not significantly different between the groups. CONCLUSION: The data demonstrate
      that laparoscopic colectomy is a cost-effective means of electively managing
      sigmoid diverticular disease. This operative approach may become very important
      in an era of increasing constraints on hospital occupancy rates and access to
      nursing services in many regions of the country.

PMID- 12006931
TI  - Long-term survival after laparoscopic colon resection for cancer: complete five
      year follow-up.
AB  - PURPOSE: The role of laparoscopic surgery in the cure of colorectal cancer is
      controversial. The aim of this study was to evaluate long-term survival after
      curative, laparoscopic resection of colorectal cancer. Specifically, we wanted to
      review those patients who now had complete five-year follow-up. METHODS: One
      hundred two consecutive patients (March 1991 to March 1996) underwent
      laparoscopic colon resections for cancer at one institution and now have complete
      five-year survival data. Charts were retrospectively reviewed and results
      compared with conventional surgery, i.e., open colectomy at our institution, and
      with the National Cancer Data Base during a similar time period. RESULTS: Fifty
      nine male and 43 female patients with an average age of 70 (range, 34-92) years
      made up the study. Complications occurred in 23 percent of patients, and one
      patient died (1 percent). Forty-four laparoscopic right colectomies, 2 transverse
      colectomies, 36 laparoscopic left or sigmoid colectomies, 15 laparoscopic low
      anterior resections, and 5 laparoscopic abdominoperineal resections were
      performed. The average number of lymph nodes harvested was 6.6 +/- 0.61 (range, 0
      22). Eight cases (7.8 percent) were "converted to open"; i.e., the typical 6-cm
      extraction site was lengthened to complete mobilization, devascularization,
      resection, or anastomosis, or a separate incision was required to complete the
      procedure. There was one extraction-site recurrence and one port-site recurrence;
      both occurred before the routine use of plastic-sleeve wound protection. The mean
      follow-up for laparoscopic colon resection patients was 64.4 +/- 2.8 (range, 1
      111) months. According to the TNM classification system, 27 patients had Stage I
      cancer, 37 had Stage II, 23 had Stage III, and 15 had Stage IV. Similar five-year
      survival rates for laparoscopic and conventional surgery for cancer were noted.
      The five-year relative survival rates in the laparoscopic colon resection group
      were 73 percent for Stage I, 61 percent for Stage II, 55 percent for Stage III,
      and 0 percent for Stage IV. The five-year relative survival rates for the open
      colectomy and National Cancer Data Base groups were 75 and 70 percent,
      respectively, for Stage I, 65 and 60 percent for Stage II, 46 and 44 percent for
      Stage III, and 11 and 7 percent for Stage IV. CONCLUSIONS: Laparoscopic colon
      resection for cancer is safe and feasible in a private setting. Our data suggest
      that long-term survival after laparoscopic colon resection for cancer is similar
      to survival after conventional surgery. Prospective, randomized trials presently
      under way will likely confirm these results.

PMID- 12006932
TI  - Activity of HspE7, a novel immunotherapy, in patients with anogenital warts.
AB  - PURPOSE: Human papillomavirus causes anogenital squamous intraepithelial lesions,
      warts, and cancer. Treatment of squamous intraepithelial lesions to prevent
      cancer often requires extensive surgery. We tested a human papillomavirus
      specific immunotherapy, HspE7, as a potential alternative. METHODS: HspE7 was
      constructed by fusing heat shock protein Hsp65 from bacille Calmette-Guerin to E7
      protein from human papillomavirus-16. Improvement in pathologic diagnosis of
      patients with persistent high-grade squamous intraepithelial lesions was studied
      in an open-label trial (HspE7 500 microg monthly x3). Anogenital warts were not a
      trial parameter, but a retrospective review of the medical records of the first
      22 patients enrolled at one site was undertaken to estimate the quality and
      frequency of responses of anogenital warts. Patients with warts by physical
      examination at baseline were scored at 24 weeks as to the percent reduction in
      wart size. RESULTS: Fourteen of the 22 patients had warts at baseline. At Week
      24, 3 of the 14 patients had complete resolution of their warts, and 10 had warts
      reduced in size an estimated 70 to 95 percent. The remaining patient's warts
      increased in size. The reduction in size in most patients greatly diminished the
      procedure necessary for complete ablation. No serious or severe adverse events
      were related to HspE7. CONCLUSIONS: A retrospective review of patients' medical
      records suggests that HspE7 may be broadly active in anogenital warts. This
      activity crosses multiple human papillomavirus types. The warts improved
      substantially but usually did not totally disappear within six months. Patient
      follow-up continues. A new randomized, placebo-controlled trial is underway to
      evaluate these findings.

PMID- 12006933
TI  - Comparison of quality of life and anorectal function after artificial sphincter
      implantation.
AB  - PURPOSE: Quality of life, a major outcome parameter in the treatment of anal
      incontinence, has not been assessed after artificial sphincter implantation. The
      purpose of this single-center, prospective, nonrandomized study was to assess
      quality-of-life differences in patients before and after artificial sphincter
      implantation and compare them with clinical incontinence scores and anal
      manometry. METHODS: Quality of life was assessed in 16 patients (14 females; mean
      age, 43 years) consecutively implanted with an Acticon Neosphincter. The Fecal
      Incontinence Quality of Life Scale, a quality-of-life instrument specifically
      designed for analysis of anal incontinence, included 27 items grouped in four
      domains: lifestyle, coping/behavior, depression/self-perception, and
      embarrassment. Fecal Incontinence Quality of Life Scale score (0 to 1, with 1
      indicating better quality of life) was calculated preoperatively and
      postoperatively and compared with the Fecal Incontinence Score (on a scale of 0
      to 120, with 120 being complete incontinence), an evacuation score, and maximal
      resting pressure. RESULTS: At a mean (standard deviation) of 25 (15) months,12
      patients had an activated device, and 11 had satisfactory anorectal function.
      Significant improvement was observed postoperatively in the four separate quality
      of-life domains. Mean (standard deviation) Fecal Incontinence Quality of Life
      Scale scores increased from 0.44 (0.14) preoperatively to 0.86 (0.18), 0.94
      (0.06), and 0.83 (0.16) at 6, 12, and 24 months after implantation, respectively.
      For the same time periods, the mean (standard deviation) Fecal Incontinence
      Scores were 105 (14), 24 (26), 32 (35), and 32 (28), respectively (P< 0.05). A
      linear correlation was found between the improvement over time in quality of life
      measured by the Fecal Incontinence Quality of Life Scale and clinical evaluation
      of incontinence measured by the Fecal Incontinence Score (r2 = 0.97; P = 0.03).
      Mean (standard deviation) maximal resting pressure increased similarly from 42
      (24) cm H2O preoperatively to 97 (23) cm H2O at the end of follow-up (P <
      0.0001). CONCLUSION: After artificial sphincter implantation, quality of life as
      assessed by a new Fecal Incontinence Quality of Life Scale instrument was
      significantly improved. These results correlated with clinical assessment of anal
      incontinence and were associated with a significant increase in maximal anal
      resting pressure on manometry.

PMID- 12006934
TI  - Early identification of peritonitis by peritoneal cytokine measurement.
AB  - PURPOSE: The assessment of plasma cytokine levels adds a useful tool to the
      diagnostic measures in severe inflammatory diseases. Proinflammatory cytokine
      levels in abdominal fluid after abdominal surgery have been shown to far exceed
      plasma cytokine levels. Thus, we investigated the local release of interleukin
      1beta, interleukin 6, and tumor necrosis factor-alpha in patients after
      colorectal surgery during the early postoperative period to evaluate whether it
      may serve as an indicator of evolving peritonitis. METHOD: In a prospective,
      observational pilot study, the first 12 consecutive patients who did not develop
      any postoperative complications (Group I), and the first 12 patients with
      secondary peritonitis caused by an anastomotic leakage (Group II), were included
      in the study. Interleukin 6, interleukin 1beta, and tumor necrosis factor-alpha
      levels were determined in the abdominal exudate and compared between the groups
      within the first four days after colorectal surgery. RESULTS: Abdominal fluid
      interleukin 6 levels in Group II patients were higher (162,500 +/- 105,800 pg/ml)
      as early as the first postoperative day compared with Group I (27,940 +/- 13,860
      pg/ml; P < 0.0001); this lasted for the whole observation period. The same
      applies to tumor necrosis factor-alpha levels (461.4 +/- 167.8 pg/ml vs. 175.8 +/
      178.6 pg/ml on day 1; P = 0.0007). The difference in interleukin 1beta cytokine
      levels became statistically significant on the third postoperative day. Moreover,
      abdominal fluid cytokine levels rose in Group II, whereas they remained virtually
      unchanged or even tended to decrease over time in Group I. CONCLUSION: We suggest
      that the estimation of the peritoneal cytokine levels might be an additional
      diagnostic tool that can support the early recognition of peritonitic
      complications in colorectal surgery.

PMID- 12006935
TI  - Abdominal colporectopexy with pelvic cul-de-sac closure.
AB  - PURPOSE: Rectal prolapse and posthysterectomy vaginal vault prolapse often occur
      together and constitute a management problem. This article describes a combined
      colorectal and gynecologic approach to surgical management and reports the follow
      up results of treatment. METHOD: Patients who presented with both rectal and
      gynecologic symptoms of prolapse subsequent to hysterectomy and were found on
      clinical examination to have overt and/or occult prolapse of both the rectum and
      the vaginal vault were considered suitable for a combined operative procedure.
      This consisted of an abdominal "mesh" rectopexy, abdominal closure of the pelvic
      cul-de-sac (enhanced by intravaginal endoscopic transillumination), and a
      colpopexy attaching forward extensions of the same mesh to the apex of the
      anatomically restored and reinforced vaginal vault. The operation was also
      accompanied by a colporrhaphy if prolapse of the lower one-third of the vagina
      was still evident on completion of the abdominal procedures. RESULTS: Eighty-nine
      patients underwent combined surgery. Sixty of these patients had a concurrent
      vaginal repair. The mean follow-up time was approximately five years. There were
      no perioperative deaths, and the morbidity rate was 9 percent. No injury occurred
      to the urinary tract, and no wound or pelvic infections were evident. There was
      no recurrence of either the rectal or vaginal vault prolapse. Improvement
      occurred in all major symptoms, especially in pelvic pain. CONCLUSIONS: The
      problem of coexisting rectal and posthysterectomy vaginal vault prolapse can be
      corrected by combined abdominal colporectopexy and closure of the pelvic cul-de
      sac. For 89 patients this operation provided considerable relief of symptoms,
      with no evidence of recurrence of rectal or vaginal vault prolapse at follow-up.

PMID- 12006938
TI  - Phosphodiesterase inhibitors cause relaxation of the internal anal sphincter in
      vitro.
AB  - PURPOSE: Pharmacologic treatments are gaining widespread acceptance as first-line
      therapy for anal fissure. However, existing treatments have limited clinical
      usefulness because of side effects and incomplete healing rates. METHODS: Fresh
      human surgical resection specimens containing internal anal sphincter and rectal
      circular muscle were collected. Strips of smooth muscle were cut from each muscle
      group and mounted in a superfusion organ bath. The effects of increasing
      concentrations of phosphodiesterase inhibitors were evaluated. RESULTS: All
      phosphodiesterase inhibitors tested caused a dose-dependent reduction in the tone
      of the internal anal sphincter, with potencies as follows: vinpocentine
      (phosphodiesterase-1 inhibitor; 50 percent maximum inhibition concentration =
      0.87 +/- 0.10 microM), erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride
      (phosphodiesterase-2 inhibitor; 32 +/- 4.8 microM), trequinsin (phosphodiesterase
      3 inhibitor; 0.28 +/- 0.041 microM), rolipram (phosphodiesterase-4 inhibitor; 63
      +/- 9 microM), zaprinast (phosphodiesterase-1,5,6,9,11 inhibitor; 3 +/- 0.69
      microM), and dipyridamole (phosphodiesterase-5,6,8,10,11 inhibitor; 5.5 +/- 2
      microM). Although all inhibitors were also effective on rectal circular muscle
      strips, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, trequinsin, and
      rolipram were at least an order of magnitude more potent in this tissue than in
      the internal anal sphincter. CONCLUSIONS: There are several functionally
      important phosphodiesterases in the internal anal sphincter and rectal circular
      muscle. Both adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic
      monophosphate appear to be important in the myogenic tone of the internal anal
      sphincter, and this study provides further evidence of the sphincteric
      specialization of this tissue. Phosphodiesterase inhibitors might represent a new
      therapy for the treatment of anal fissure.

PMID- 12006939
TI  - Increased membrane type 1 matrix metalloproteinase expression from adenoma to
      colon cancer: a possible mechanism of neoplastic progression.
AB  - PURPOSE: Membrane type 1 matrix metalloproteinase is a membrane-associated matrix
      metalloproteinase central to the degradation of basement membrane components via
      the activation of matrix metalloproteinase-2. Although membrane type 1 matrix
      metalloproteinase is overexpressed in invasive colon cancer, its expression in
      colonic polyps and carcinoma in situ has not been defined. In addition, the
      association of membrane type 1 matrix metalloproteinase expression by a primary
      tumor and recurrence of colon cancers has not been examined. METHODS:
      Immunoperoxidase staining was performed on randomly selected specimens containing
      adenoma (n = 17), carcinoma in situ (n = 9), or metastatic colon carcinoma (n =
      8) with mouse monoclonal antibody to human membrane type 1 matrix
      metalloproteinase. Similar staining was also performed on randomly selected node
      negative colon cancers that recurred within five years of resection (n = 17),
      matched for age, gender, stage, grade, and vascular, lymphatic, and perineural
      invasion, and node-negative colon cancers that did not recur within five years of
      resection (n = 17). Staining for membrane type 1 matrix metalloproteinase was
      graded. Mean scores for the groups were compared by Wilcoxon test. RESULTS: We
      found a progressive and significant increase in the mean score of membrane type 1
      matrix metalloproteinase from normal mucosa to adenoma (P < 0.001), carcinoma in
      situ (P < 0.006), and invasive cancer (P < 0.009). However, there was no
      difference in membrane type 1 matrix metalloproteinase expression between the
      recurrent and nonrecurrent groups of node-negative colon cancer (P = not
      significant). CONCLUSIONS: These data suggest that membrane type 1 matrix
      metalloproteinase expression increases with progression from normal mucosa to
      invasive adenocarcinoma; however, it cannot be used as a prognostic indicator on
      which adjuvant therapy is based in node-negative colon cancer because of its
      failure to predict recurrence in this patient group.

PMID- 12006940
TI  - Activation capacity of the alternative and classic complement pathways in
      patients operated on for colorectal cancer.
AB  - PURPOSE: Tumor cells may suppress activation of the host's complement system, and
      the functional state of the complement system may be a prognostic marker of
      outcome in patients with malignancies. Serial plasma samples from patients
      undergoing intended curative surgery for colorectal cancer were analyzed for
      complement factor C3 activation capacity. METHODS: Samples were collected from 91
      patients with colorectal cancer and 13 with benign colorectal diseases before
      surgery and 1, 2, and 7 days after surgery, between 8 and 13 days after surgery,
      and 3, 6, 12, 18, 24, 36, 48, and 60 months after surgery. The samples were
      analyzed with an enzyme-linked immunosorbent assay that measured C3 activation
      capacity by the alternative and classic complement pathways. Cancer patients were
      compared according to Dukes stage, type of surgery performed, transfusion of
      blood, development of infection, venous thromboembolism, and cancer recurrence.
      RESULTS: Plasma samples obtained from cancer patients before surgery showed C3
      activation capacities corresponding to those of samples from patients with benign
      disease. For both patient groups, C3 activation capacity decreased after surgery
      and normalized within seven days. Significant differences in C3 activation
      capacities were observed between cancer patients that were related to Dukes stage
      and in patients with and without buffy coat-depleted red cells suspended in
      saline, adenine, glucose, and mannitol transfusion, infectious events, and deep
      venous thromboembolism. Measurement of C3 activation capacity was of predictive
      value in patients who developed infection. CONCLUSION: Serial measurements of C3
      activation capacity in plasma from patients who had undergone surgery for
      colorectal cancer revealed significant differences related to Dukes staging after
      surgery and to the development of infections but not to cancer recurrence.

PMID- 12006941
TI  - Intestinal anastomoses from diabetic rats contain supranormal levels of
      gelatinase activity.
AB  - PURPOSE: Early postoperative strength in intestinal anastomoses is reduced in
      diabetic rats, whereas collagen deposition is essentially unchanged, suggesting
      that increased matrix degradation may be the cause of diminished wound strength.
      The aim of this study was to investigate whether (gelatin-degrading) matrix
      metalloproteinase activity is enhanced in intestinal anastomoses from diabetic
      rats. METHODS: Sixty male young adult Wistar rats underwent resection and
      anastomosis of both ileum and colon. In half the animals diabetes was induced
      seven days before operation by streptozotocin injection (50 mg/kg intravenously).
      Gelatinase activities in extracts from uninjured intestine and anastomoses at
      one, three, or seven days after surgery were measured by quantitative gelatin
      zymography. RESULTS: After surgery, profound changes were observed with time for
      gelatinase activities with molecular weights of 50 and 60 kDa, thought to
      represent matrix metalloproteinase-2, and of 66, 80, 105, 140, 220, and 260 kDa,
      thought to represent various forms of matrix metalloproteinase-9. In many cases,
      specific activities were significantly (P < 0.05) higher in the anastomotic
      extracts from diabetic rats. Total anastomotic activities present at Day 7 were
      strongly elevated for most matrix metalloproteinase forms in ileum and colon from
      diabetic animals. CONCLUSION: Experimental diabetes leads to a sustained and
      elevated presence of gelatinase activity in intestinal anastomoses. Increased
      local matrix degradation may contribute significantly to impaired anastomotic
      strength in the intestine observed under this condition.

PMID- 12006942
TI  - Inflammatory cutaneous metastasis from rectal adenocarcinoma: report of a case.

PMID- 12006943
TI  - Intramural hematoma of the cecum: report of two cases.
AB  - Intramural hematoma of the cecum is a rare complication of blunt abdominal
      trauma. We report two patients who presented with cecal hematoma after a fall and
      a traffic accident, respectively. Diagnosis was by abdominal computed tomographic
      scan. Patients were operated on 24 and 36 hours after the injury because of
      sudden clinical deterioration and hemoperitoneum, respectively. The patients had
      a large cecal intramural hematoma that progressed to the ascending colon by
      dissection of the teniae coli. Emergency right hemicolectomy was followed by
      uneventful recovery in both patients. Only six previously reported cases of cecal
      intramural hematoma were found, and in all cases a right hemicolectomy was
      performed. In conclusion, in contrast to hematomas located in other sections of
      the gastrointestinal tract, early surgical treatment for intramural hematoma of
      the cecum is recommended.

PMID- 12006944
TI  - Pneumorrhachis, subcutaneous emphysema, pneumomediastinum, pneumopericardium, and
      pneumoretroperitoneum after proctocolectomy for ulcerative colitis: report of a
      case.
AB  - This article presents the first known case of pneumorrhachis (spinal air),
      pneumomediastinum, pneumopericardium, pneumoretroperitoneum, and subcutaneous
      emphysema after proctocolectomy for ulcerative colitis. We review the patient's
      medical history, clinical and laboratory findings, radiographic data, and
      operative records, as well as the relevant literature. We describe the case of a
      young male with ulcerative colitis who developed pneumorrhachis, subcutaneous
      emphysema, pneumoretroperitoneum, pneumomediastinum, and pneumopericardium after
      a proctocolectomy with ileal pouch-anal anastomosis. Unlike the case we report,
      previously described episodes of pneumomediastinum and subcutaneous emphysema in
      patients with ulcerative colitis developed before operative intervention. We
      offer possible explanations for these unusual complications based on analysis of
      this case and thorough review of the literature.

PMID- 12006945
TI  - Stapled anopexy and stapled hemorrhoidectomy: two opposite concepts and
      procedures.

PMID- 12006946
TI  - Excellence in teaching: what does it cost? How can we pay for it?

PMID- 12006947
TI  - Preventing kernicterus: almost there.

PMID- 12006948
TI  - Orthostatic intolerance and chronic fatigue syndrome: new light on an old
      problem.

PMID- 12006949
TI  - Arginine supplementation and the prevention of necrotizing enterocolitis in very
      low birth weight infants.

PMID- 12006950
TI  - A point well taken.

PMID- 12006951
TI  - Achieving genetic potential for nutrition and growth in cystic fibrosis.

PMID- 12006952
TI  - System-based approach to management of neonatal jaundice and prevention of
      kernicterus.

PMID- 12006953
TI  - Orthostatic intolerance in pediatrics.

PMID- 12006954
TI  - Impaired postural cerebral hemodynamics in young patients with chronic fatigue
      with and without orthostatic intolerance.
AB  - OBJECTIVES: To measure postural changes in cerebral hemodynamics in young
      patients with chronic fatigue with and without orthostatic intolerance. STUDY
      DESIGN: We studied 28 patients (age, 10 to 22 years) and 20 healthy control
      subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and
      deoxygenated Hb were noninvasively and continuously measured with near infrared
      spectroscopy during active standing. Beat-to-beat arterial pressure was monitored
      by Finapres. RESULTS: Orthostatic intolerance determined by cardiovascular
      responses to standing was observed in 16 of 28 patients: instantaneous
      orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural
      orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared
      spectroscopy at the onset of active standing was not found in 15 of 16 patients
      with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with
      chronic fatigue without orthostatic intolerance but only in 2 of 20 control
      subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged
      reduction in oxy-Hb during standing. CONCLUSIONS: Impaired cerebral hemodynamics
      in patients with chronic fatigue syndrome and postural orthostatic tachycardia
      suggest a link between impaired cerebral oxygenation and chronic fatigue.
      However, this cannot explain the symptoms in patients meeting the criteria of
      chronic fatigue without orthostatic intolerance.

PMID- 12006955
TI  - Transient orthostatic hypotension is common in adolescents.
AB  - OBJECTIVES: We hypothesized that transient hypotension associated with the
      symptom of lightheadedness with standing is a common phenomenon in healthy
      adolescents but may be mistaken for orthostatic intolerance. STUDY DESIGN: We
      studied 23 healthy adolescents, combining upright tilt to 70 degrees and to 35
      degrees (in 12 patients) with continuous heart rate and blood pressure (BP)
      measurements. We measured peripheral blood flow and venous pressure in the arms
      and legs by using venous plethysmography. RESULTS: Healthy subjects with normal
      vasoconstrictive responses to sustained upright tilt uniformly have a transient
      fall in BP during 70 degrees upright tilt that varies from almost undetectable to
      large decreases in BP easily exceeding the 20-mm Hg threshold for orthostatic
      hypotension. Large decreases are associated with short-lived symptoms of
      lightheadedness and are most marked in those with the largest calf blood flow.
      The higher the flow, the lower the BP falls. There is appropriate reflex
      tachycardia. CONCLUSIONS: We conclude that transient orthostatic hypotension is
      common in many healthy adolescents, especially after prolonged recumbency, and is
      related to dependent vascular tone.

PMID- 12006956
TI  - Arginine supplementation prevents necrotizing enterocolitis in the premature
      infant.
AB  - OBJECTIVES: To determine whether supplementation with L -arginine reduces the
      incidence of all stages of necrotizing enterocolitis (NEC) in premature infants
      with birth weight < or =1250 g and gestational age < or =32 weeks. STUDY DESIGN:
      In a randomized, double-blind, placebo-controlled study, 152 premature infants
      were prospectively, randomly assigned to receive either supplemental L -arginine
      (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group
      B]) with oral feeds/parenteral nutrition during the first 28 days of life.
      Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were
      measured in all infants at days 3, 14, and 28 and at the time of diagnosis of
      NEC. RESULTS: NEC developed in 5 infants in group A compared with 21 infants in
      group B (P <.001). Arginine intake and plasma arginine concentrations were
      similar in both groups at study entry and (as expected) increased in group A at
      days 14 and 28. Plasma arginine concentrations were lower in both groups at time
      of diagnosis of NEC. No significant differences in maternal and neonatal
      demographics, nutrient intake, plasma ammonia and total and essential amino acid
      concentrations were present between the two groups. CONCLUSIONS: Arginine
      supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence
      of all stages of NEC.

PMID- 12006957
TI  - A national point-prevalence survey of pediatric intensive care unit-acquired
      infections in the United States.
AB  - OBJECTIVE: To determine the prevalence of intensive care unit-acquired
      infections, a major cause of morbidity in pediatric intensive care unit (PICU)
      patients. METHODS: Pediatric Prevention Network hospitals (n = 31) participated
      in a point-prevalence survey on August 4, 1999. Data collected for all PICU
      inpatients included demographics, infections, therapeutic interventions, and
      outcomes. RESULTS: There were 512 patients in 35 PICUs. The median age was 2.2
      years (range, <1 day-35.4 years). Seventy-five PICU-acquired infections occurred
      among 61 (11.9%) patients. The most frequently reported sites were bloodstream
      (31 [41.3%]), lower respiratory tract (17 [22.7%]), urinary tract (10 [13.3%]),
      or skin/soft tissue (6 [8.0%]). The most frequent pathogens were coagulase
      negative staphylococci (in 16 [21.3%] infections), Candida spp. (13 [17.3%]),
      enterococci (10 [13.3%]), Staphylococcus aureus (9 [12.0%]), or Pseudomonas
      aeruginosa (8 [10.7%]). Age-adjusted risk factors for infection included central
      intravenous catheters (relative risk [RR], 4.1; 95% confidence intervals [CI],
      2.4-7.1), arterial catheters (RR, 2.4; 95% CI, 1.5-3.9), total parenteral
      nutrition (RR, 5.5; 95% CI, 3.6-8.5), or mechanical ventilation (RR, 3.9; 95% CI,
      2.2-6.8). Infection was associated with higher age-adjusted risk of death within
      4 weeks of the survey (RR, 3.4; 95% CI, 1.7-6.5). CONCLUSIONS: This national
      multicenter study documented the high prevalence of PICU-acquired infections.
      Preventing these infections should be a national priority.

PMID- 12006958
TI  - Effects of megestrol acetate on weight gain, body composition, and pulmonary
      function in patients with cystic fibrosis.
AB  - OBJECTIVES: Malnutrition is a negative prognostic indicator in patients with
      cystic fibrosis (CF) and may accentuate pulmonary decline. We tested whether
      megestrol acetate would have beneficial effects on growth in patients with CF and
      pancreatic insufficiency. STUDY DESIGN: We performed a randomized, double-blind,
      placebo controlled study. All patients were taking replacement enzymes to
      compensate for pancreatic insufficiency. Patients (n = 17) were randomly assigned
      to receive either megestrol acetate or placebo. RESULTS: The treatment group had
      a significant increase in weight-for-age z scores compared with placebo and
      reached 100% of their ideal body weight within 3 months of initiating therapy.
      Weight gain included both fat and fat-free mass. Improved pulmonary function
      (forced vital capacity and forced expiratory volume in 1 second) was noted in the
      treatment group compared with placebo (P <.04). Reversible adrenal suppression
      was observed in the majority of patients who received megestrol acetate.
      CONCLUSIONS: Short-term use of megestrol acetate results in significant weight
      gain and improved pulmonary function in malnourished subjects with CF. Our study
      provides a controlled basis for this intervention, identifies important side
      effects, and provides the foundation for multiyear, longitudinal trials in a
      larger number of patients with CF.

PMID- 12006959
TI  - Results of early reevaluation of growth hormone secretion in short children with
      apparent growth hormone deficiency.
AB  - OBJECTIVE: To test the hypothesis that normalization of the growth hormone (GH)
      response to stimulation in patients with GH deficiency (GHD) and normal magnetic
      resonance imaging (MRI) of the hypothalamic-pituitary area might occur earlier
      than at attainment of final height. STUDY DESIGN: Prepubertal children with short
      stature (21 boys and 12 girls; age, 5.2-10 years), in whom a diagnosis of GHD was
      based on a GH response <10 microg/L after 2 pharmacologic tests (clonidine,
      arginine, or insulin hypoglycemia), and normal MRI of the hypothalamic-pituitary
      area were studied. After 1 to 6 months, all children underwent reevaluation of GH
      secretion by means of one of the provocative tests previously used. During that
      time, none of the children received GH therapy or entered puberty. RESULTS: A GH
      response > or =10 microg/L after retesting was found in 28 patients, and a GH
      response <10 microg/L was found in 5. In 9 patients, the peak GH response at
      diagnosis was <7 microg/L to both tests used. In 8, the GH response at retesting
      was > or =10 microg/L and was 9.0 microg/L in the remaining child. CONCLUSIONS:
      We suggest that patients with pathologic GH responses to provocative tests but
      normal MRI should be reevaluated and followed up before a diagnosis of GHD is
      firmly established.

PMID- 12006960
TI  - Early treatment with intravenous immunoglobulin in patients with Kawasaki
      disease.
AB  - OBJECTIVES: To determine if a shorter interval between Kawasaki disease (KD)
      treatment with intravenous immunoglobulin (IVIG) and fever onset results in
      increased treatment failures, need for adjunctive therapy, or development of
      coronary artery lesions. STUDY DESIGN: Patients with KD (n = 178; 89 matched
      pairs) diagnosed between 1987 and 1999 were included in this case-control study.
      All patients had fever plus at least 4 of the 5 clinical criteria for KD. Eighty
      nine patients who received IVIG at day 5 or earlier were matched to patients
      diagnosed within 4 weeks and given IVIG at days 6 to 9 of fever. Compiled data
      from a detailed chart review included demographics, clinical features, fever
      duration, investigations, disease course, and response to therapy. Differences
      between matched case and control pairs were analyzed by means oft tests and
      McNemar tests. RESULTS: No demographic differences were noted between the two
      groups. Patients treated on day 5 or less of fever had a shorter total fever
      duration (5.2 +/- 1.9 days vs 8.0 +/- 1.8 days, P <.0001), longer fever after
      IVIG treatment (1.5 +/- 1.9 days vs 0.8 +/- 1.3 days, P =.008), and less coronary
      artery ectasia at 1 year after KD onset (4% vs 16%, P =.02). There was no
      significant difference between cases and control patients in the number of
      patients with KD recrudescence, need for repeat courses of IVIG, need for
      corticosteroids, length of hospitalization, or development of coronary artery
      aneurysms within the first 3 months. Patients who were treated on day 5 or less
      of fever had higher levels of serum albumin (36 +/- 5 g/L vs 33 +/- 5 g/L, P
      <.01) and serum ALT (115 +/- 155 U/L vs 46 +/- 49 U/L, P <.001) as well as a
      lower platelet count (354 +/- 131 vs 403 +/- 166, P =.02) than did control
      patients during the acute phase. CONCLUSIONS: Early treatment of KD resulted in
      less coronary ectasia at 1 year after KD onset but was not associated with a
      quicker resolution of fever, an increased number of treatment failures, an
      increased need for adjunctive therapy, length of hospitalization, nor development
      of coronary artery lesions. In children with fever and classic clinical and
      laboratory findings of KD, treatment with IVIG on or before 5 days of fever
      resulted in better coronary outcomes and decreased the total length of time of
      clinical symptoms.

PMID- 12006961
TI  - QT interval dispersion in young women with anorexia nervosa.
AB  - OBJECTIVES: To evaluate the degree of QT dispersion in a group of young women in
      the starvation phase of anorexia nervosa (AN) and its relation to left
      ventricular (LV) mass. STUDY DESIGN: Sixteen patients with self-induced
      starvation were matched with 16 women of normal weight and 16 constitutionally
      thin women (body mass index <20 kg/m2). Starving patients and control patients
      underwent an electrocardiogram and echocardiogram. QT intervals were measured
      from surface electrocardiograms and QT dispersion was defined as the difference
      between maximum QT and minimum QT occurring in any of the 12 leads. RESULTS: LV
      chamber mass was significantly less in women with AN than in thin and normal
      weight women. QT dispersion was significantly greater in AN than in the thin and
      control groups (QT dispersion: 50 +/- 14 vs 34 +/- 9 and 37 +/- 11 ms, P <.001;
      QT interval dispersion corrected for heart rate: 49+12 vs 34 +/- 9 and 36 +/- 7
      ms, P <.01, respectively). A significant relation between QT dispersion and LV
      mass index (r = -0.726, P <.01), and between QTc dispersion and LV mass index (r
      = -0.693, P < 0.01) were found only in the patients with AN. CONCLUSION: Starving
      patients show an increased QT dispersion related to reduced LV mass. This result
      could represent a useful indicator of arrhythmic risk and sudden death in AN.

PMID- 12006962
TI  - Sudden unexpected death in hospitalized children.

PMID- 12006963
TI  - Asymptomatic morgagni hernia in a neonate.

PMID- 12006964
TI  - Bone metabolism in children with epidermolysis bullosa.
AB  - We evaluated bone mineral density, vitamin D status, and biochemical markers of
      bone turnover in seven children with epidermolysis bullosa (EB). Four had
      osteopenia (Z score, -1.5) and four 25(OH) vitamin D <34 nmol/L (14 ng/mL), two
      of which had hyperparathyroidism. Children with severe EB should have evaluation
      of bone metabolism.

PMID- 12006965
TI  - Outcome of Crohn's disease diagnosed before two years of age.
AB  - We describe the course of 7 patients younger than 2 years with Crohn's disease.
      Prolonged remission was achieved medically (5) or surgically (1), whereas one
      patient died of disseminated adenovirus. Three had malnutrition and growth
      failure. Crohn's disease very early in life does not always imply a poor
      prognosis; however, significant morbidity and mortality are encountered.

PMID- 12006966
TI  - Gastroesophageal reflux disease and dental erosion in children.
AB  - Recurrent exposure to gastric acid as in children with bulimia and
      gastroesophageal reflux disease (GERD) may contribute to dental erosion. We
      performed a prospective study to evaluate the presence of GERD and dental
      erosions in children with primary and permanent dentition. Children undergoing
      elective endoscopy for possible GERD (n = 37) underwent evaluation of their teeth
      for the presence, severity, and pattern of erosion and stage of dentition: 24
      patients had GERD. Dental erosions were identified in 20; all had GERD. Erosion
      patterns showed more involvement of the posterior teeth. Many affected patients
      had primary dentition.

PMID- 12006967
TI  - Impact of repeated surgical procedures on the incidence and prevalence of latex
      allergy: a prospective study of 1263 children.
AB  - Assessment with questionnaire, skin tests, and immunoglobulin E measurements
      showed 6 (0.5%) of 1263 children having elective surgery had latex allergy; 50
      (4%) others were latex-sensitized. Any previous operation increased the odds of
      latex sensitization by 13 times; multiple operations had a less marked effect.
      All children having surgery may need primary prophylaxis for latex.

PMID- 12006968
TI  - Treatment failures in children with asthma due to inappropriate use of
      Turbuhaler.

PMID- 12006969
TI  - New drug treatment for asthma: clinical versus statistical significance.

PMID- 12006970
TI  - Failure of naloxone to reverse brimonidine-induced coma in an infant.

PMID- 12006971
TI  - Antenatal glucocorticoid treatment increases the rate of "survival without
      chronic lung disease" among 25- to 29-week preterm infants.

PMID- 12006972
TI  - Early versus late treatment of PDA with indomethacin.

PMID- 12006973
TI  - Fluticasone for obstructive sleep apnea.

PMID- 12006974
TI  - T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells.
AB  - T helper type 1 (T(H)1) cell development involves interferon-gamma (IFN-gamma)
      signaling through signal transducer and activator of transcription 1 (STAT1) and
      interleukin-12 (IL-12) signaling through STAT4 activation. We examined here T-bet
      regulation and evaluated the actions of T-bet in STAT1- and STAT4-dependent T(H)1
      development processes. We found that T-bet expression during T cell activation
      was strongly dependent on IFN-gamma signaling and STAT1 activation, but was
      independent of STAT4. Ectopic T-bet expression strongly increased IFN-gamma
      production in T(H)2 cells activated by PMA-ionomycin, but weakly increased IFN
      gamma production in T(H)2 cells stimulated by IL-12 IL-18 or OVA peptide antigen
      presenting cell stimulation. In contrast, IL-12 IL-18 induced IFN-gamma
      production remained STAT4-dependent despite ectopic T-bet expression. Ectopic T
      bet expression selectively induced expression of IL-12Rbeta2, but not IL
      18Ralpha, in wild-type and STAT1(-/-) T(H)2 cells, but did not extinguish
      expression of GATA-3 and T(H)2 cytokines. Finally, ectopic T-bet did not directly
      induce expression of endogenous T- bet independently of IFN-gamma or STAT1. Thus,
      T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation. In
      addition, T-bet mediates STAT1-dependent processes of T(H)1 development,
      including the induction of IL-12Rbeta2.

PMID- 12006975
TI  - Signaling via LTbetaR on the lamina propria stromal cells of the gut is required
      for IgA production.
AB  - Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) are thought to be
      essential for immunoglobulin A (IgA) production. We found that the severe IgA
      deficiency in lymphotoxin-deficient (LT(-/-)) mice could be fully reversed by
      reconstitution with LT-expressing bone marrow, despite the absence of both LNs
      and PPs. The number of IgA precursors from LT(-/-) mice was not reduced, and they
      were able to migrate into the lamina propria (LP) of wild-type mice but not of
      LTbetaR(-/-) mice. Consistently, lymphoid tissue chemokines and adhesion
      molecules were reduced within the LP of LTalpha(-/-) and LTbetaR(-/-) mice. IgA
      deficiency in LTalpha(-/-) mice was reversed by the transplantation of a segment
      of RAG-1 (recombination-activating gene 1) deficient intestine, which confirmed
      the dispensability of the MLNs and PPs and the sufficiency of the LT-mediated gut
      microenvironment for IgA production.

PMID- 12006976
TI  - In vivo developmental stages in murine natural killer cell maturation.
AB  - Natural killer (NK) cells develop in the bone marrow, but their in vivo stages of
      maturation, expansion and acquisition of receptors that guide target cell
      specificity are not well defined. We describe here such stages of development. We
      also show that developing NK cells actively proliferate at a phenotypically
      distinguishable immature stage after they have acquired expression of Ly49 and
      CD94-NKG2 receptors. These studies provide a developmental framework for NK cell
      maturation in vivo and suggest the possible involvement of the Ly49 and CD94-NKG2
      receptors themselves in modulating expansion of NK cell populations with a given
      NK cell receptor repertoire.

PMID- 12006977
TI  - Association of genes to genetically inherited diseases using data mining.
AB  - Although approximately one-quarter of the roughly 4,000 genetically inherited
      diseases currently recorded in respective databases (LocusLink, OMIM) are already
      linked to a region of the human genome, about 450 have no known associated gene.
      Finding disease-related genes requires laborious examination of hundreds of
      possible candidate genes (sometimes, these are not even annotated; see, for
      example, refs 3,4). The public availability of the human genome draft sequence
      has fostered new strategies to map molecular functional features of gene products
      to complex phenotypic descriptions, such as those of genetically inherited
      diseases. Owing to recent progress in the systematic annotation of genes using
      controlled vocabularies, we have developed a scoring system for the possible
      functional relationships of human genes to 455 genetically inherited diseases
      that have been mapped to chromosomal regions without assignment of a particular
      gene. In a benchmark of the system with 100 known disease-associated genes, the
      disease-associated gene was among the 8 best-scoring genes with a 25% chance, and
      among the best 30 genes with a 50% chance, showing that there is a relationship
      between the score of a gene and its likelihood of being associated with a
      particular disease. The scoring also indicates that for some diseases, the chance
      of identifying the underlying gene is higher.

PMID- 12006978
TI  - Insertional mutagenesis in zebrafish rapidly identifies genes essential for early
      vertebrate development.
AB  - To rapidly identify genes required for early vertebrate development, we are
      carrying out a large-scale, insertional mutagenesis screen in zebrafish, using
      mouse retroviral vectors as the mutagen. We will obtain mutations in 450 to 500
      different genes--roughly 20% of the genes that can be mutated to produce a
      visible embryonic phenotype in this species--and will clone the majority of the
      mutated alleles. So far, we have isolated more than 500 insertional mutants. Here
      we describe the first 75 insertional mutants for which the disrupted genes have
      been identified. In agreement with chemical mutagenesis screens, approximately
      one-third of the mutants have developmental defects that affect primarily one or
      a small number of organs, body shape or swimming behavior; the rest of the
      mutants show more widespread or pleiotropic abnormalities. Many of the genes we
      identified have not been previously assigned a biological role in vivo. Roughly
      20% of the mutants result from lesions in genes for which the biochemical and
      cellular function of the proteins they encode cannot be deduced with confidence,
      if at all, from their predicted amino-acid sequences. All of the genes have
      either orthologs or clearly related genes in human. These results provide an
      unbiased view of the genetic construction kit for a vertebrate embryo, reveal the
      diversity of genes required for vertebrate development and suggest that hundreds
      of genes of unknown biochemical function essential for vertebrate development
      have yet to be identified.

PMID- 12006979
TI  - Repair by retrotransposition.

PMID- 12006980
TI  - DNA repair mediated by endonuclease-independent LINE-1 retrotransposition.
AB  - Long interspersed elements (LINE-1s) are abundant retrotransposons in mammalian
      genomes that probably retrotranspose by target site-primed reverse transcription
      (TPRT). During TPRT, the LINE-1 endonuclease cleaves genomic DNA, freeing a 3'
      hydroxyl that serves as a primer for reverse transcription of LINE-1 RNA by LINE
      1 reverse transcriptase. The nascent LINE-1 cDNA joins to genomic DNA, generating
      LINE-1 structural hallmarks such as frequent 5' truncations, a 3' poly(A)+ tail
      and variable-length target site duplications (TSDs). Here we describe a pathway
      for LINE-1 retrotransposition in Chinese hamster ovary (CHO) cells that acts
      independently of endonuclease but is dependent upon reverse transcriptase. We
      show that endonuclease-independent LINE-1 retrotransposition occurs at near
      wildtype levels in two mutant cell lines that are deficient in nonhomologous end
      joining (NHEJ). Analysis of the pre- and post-integration sites revealed that
      endonuclease-independent retrotransposition results in unusual structures because
      the LINE-1s integrate at atypical target sequences, are truncated predominantly
      at their 3' ends and lack TSDs. Moreover, two of nine endonuclease-independent
      retrotranspositions contained cDNA fragments at their 3' ends that are probably
      derived from the reverse transcription of endogenous mRNA. Thus, our results
      suggest that LINE-1s can integrate into DNA lesions, resulting in retrotransposon
      mediated DNA repair in mammalian cells.

PMID- 12006981
TI  - Progressive induction of caudal neural character by graded Wnt signaling.
AB  - Early in differentiation, all neural cells have a rostral character. Only later
      do posteriorly positioned neural cells acquire characteristics of caudal
      forebrain, midbrain and hindbrain cells. Caudalization of neural tissue in the
      chick embryo apparently involves the convergent actions of (i) fibroblast growth
      factor (FGF) signaling and (ii) signaling from the caudal paraxial mesoderm, or
      'PMC activity', which has not yet been defined molecularly. Here we report
      evidence that Wnt signaling underlies PMC activity, and show that Wnt signals act
      directly and in a graded manner on anterior neural cells to induce their
      progressive differentiation into caudal forebrain, midbrain and hindbrain cells.

PMID- 12006982
TI  - Calcium calmodulin-dependent protein kinase IV is required for fear memory.
AB  - The ability to remember potential dangers in an environment is necessary to the
      survival of animals and humans. The cyclic AMP responsive element binding protein
      (CREB) is a key transcription factor in synaptic plasticity and memory
      consolidation. We have found that in CaMKIV(-/-) mice--which are deficient in a
      component of the calcium calmodulin-dependent protein kinase (CaMK) pathway, a
      major pathway of CREB activation--fear memory, but not persistent pain, was
      significantly reduced. CREB activation by fear conditioning and synaptic
      potentiation in the amygdala and cortical areas was reduced or blocked. We
      propose that cognitive memory related to a noxious shock can be disassociated
      from behavioral responses to tissue injury and inflammation.

PMID- 12006983
TI  - Local inhibition modulates odor-evoked synchronization of glomerulus-specific
      output neurons.
AB  - At the first stage of olfactory processing in the brain, synchronous firing
      across glomeruli may help to temporally bind multiple and spatially distributed
      input streams activated by a given odor. This hypothesis, however, has never been
      tested in an organism in which the odor-tuning properties of several spatially
      identifiable glomeruli are known. Using the sphinx moth, an insect that meets
      these specific criteria, we recorded odor-evoked responses simultaneously from
      pairs of projection neurons (PNs) innervating the same or different glomeruli in
      the macroglomerular complex (MGC), which is involved in processing pheromonal
      information. PNs that branched in the same glomerulus and were activated by the
      same pheromone component also showed the strongest coincident responses to each
      odor pulse. Glomerulus-specific PN pairs were also inhibited by the pheromone
      component that selectively activated PNs in the neighboring glomerulus, and about
      70% of all intraglomerular pairs showed increased synchronization when stimulated
      with a mixture of the two odorants. Thus, when two adjacent glomeruli receive
      their inputs simultaneously, the temporal tuning of output from each glomerulus
      is enhanced by reciprocal and inhibitory interglomerular interactions.

PMID- 12006984
TI  - Structural basis for the selective activation of Rho GTPases by Dbl exchange
      factors.
AB  - Activation of Rho-family GTPases involves the removal of bound GDP and the
      subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors
      (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases,
      Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family
      members. To rationalize this specificity, we have determined crystal structures
      of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of
      the exchange factors intersectin and Dbs in complex with their cognate GTPases,
      Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs
      reveals the key determinants responsible for promoting exchange activity in
      Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural
      features necessary for the proper pairing of Dbl-exchange factors with Rho
      GTPases and now allow for the detailed manipulation of signaling pathways
      mediated by these oncoproteins in vivo.

PMID- 12006985
TI  - Conformational strain in the hydrophobic core and its implications for protein
      folding and design.
AB  - We have designed de novo 13 divergent spectrin SH3 core sequences to determine
      their folding properties. Kinetic analysis of the variants with stability similar
      to that of the wild type protein shows accelerated unfolding and refolding rates
      compatible with a preferential stabilization of the transition state. This is
      most likely caused by conformational strain in the native state, as deletion of a
      methyl group (Ile-->Val) leads to deceleration in unfolding and increased
      stability (up to 2 kcal x mol(-1)). Several of these Ile-->Val mutants have
      negative phi(-U) values, indicating that some noncanonical phi(-U) values might
      result from conformational strain. Thus, producing a stable protein does not
      necessarily mean that the design process has been entirely successful. Strained
      interactions could have been introduced, and a reduction in the buried volume
      could result in a large increase in stability and a reduction in unfolding rates.

PMID- 12006986
TI  - Myosin V is a left-handed spiral motor on the right-handed actin helix.
AB  - Myosin V is a two-headed, actin-based molecular motor implicated in organelle
      transport. Previously, a single myosin V molecule has been shown to move
      processively along an actin filament in discrete approximately 36 nm steps.
      However, 36 nm is the helical repeat length of actin, and the geometry of the
      previous experiments may have forced the heads to bind to, or halt at, sites on
      one side of actin that are separated by 36 nm. To observe unconstrained motion,
      we suspended an actin filament in solution and attached a single myosin V
      molecule carrying a bead duplex. The duplex moved as a left-handed spiral around
      the filament, disregarding the right-handed actin helix. Our results indicate a
      stepwise walking mechanism in which myosin V positions and orients the unbound
      head such that the head will land at the 11th or 13th actin subunit on the
      opposing strand of the actin double helix.

PMID- 12006987
TI  - Cloning, expression and immunization of the new antigen gene Sj-Ts4 of
      Schistosoma japonicum.
AB  - In order to explore the molecular mechanism of high immune protection against
      schistosomes infection in animals infected with Trichinella spiralis, and to
      provide several cross-protective antigen genes for developing anti
      schistosomiasis vaccine, a Schistosoma japonicum adult worm cDNA library was
      immunoscreened using sera taken from mice infected with Trichinella spiralis.
      Nine positive clones were obtained after 3 rounds of immunoscreening. Among them,
      Sj-Ts4 represents a novel gene of S. japonicum, which coding for a novel protein
      of 210 amino acids. The protein has a deduced molecular mass of 23 kD and
      isoelectric point of 7.72. Sj-Ts4 was expressed as a glutathione-S-transferase
      (GST) fusion protein by cloning into the prokaryotic expression vector pGEX-5X-3.
      The recombinant Sj-Ts4 protein (rSj-Ts4) was purified and could be recognized by
      sera of mice infected with S.japonicum. Vaccination of several groups of mice
      with rSj-Ts4 or rSj-Ts4 incorporated into Freund's complete adjuvant induced high
      titers of specific IgG antibodies. Two vaccination groups all obtained
      significant reduction in worm burden (31.36%, 36.80%, P<0.01), compared with the
      control groups.

PMID- 12006988
TI  - Restoration of T cell-specific V(D)J recombination in DNA-PKcs(-/-) mice by
      ionizing radiation: The effects on survival, development, and tumorigenesis.
AB  - DNA-dependent protein kinase (DNA-PK) is a DNA-activated nuclear serine/threonine
      protein kinase. DNA-PK consists of a heterodimeric Ku subunit (composed of a 70
      and 86 kD subunit) which binds DNA ends and targets the catalytic subunit DNA
      PKcs to DNA strand breaks. DNA-PK plays a major role in the repair of double
      strand breaks (DSB) induced in DNA after exposure to ionizing radiation. To
      better understand the nature of DNA repair defect associated with DNA-PKcs
      deficiency, we have established DNA-PKcs(-/-) mouse embryo fibroblast cell lines
      and DNA-PKcs(-/-) null mice, and investigated the response of these mutant cells
      and mice to DNA damage. DNA-PKcs(-/-) cells are hypersensitive to gamma
      irradiation, as evidenced by their low survival as assayed by colony formation
      efficiencies. Consistent with the radiation hypersensitive phenotype of the cell
      lines, DNA-PKcs(-/-) mice also display an extreme radiosensitivity, characterized
      by enhanced mortality after gamma-irradiation. Treatment of newborn DNA-PKcs(-/-)
      mice with sublethal doses of ionizing radiation restores T cell receptor (TCR)
      beta recombination and T cell maturation. However, radiation does not restore B
      cell development. All these mice eventually developed thymic lymphoma. These
      observations suggest an interrelationship between DSB repair, V(D)J recombination
      and lymphomagenesis, and provide an in vivo model to elucidate the critical
      pathways between the regulation of DNA DSB repair, V(D)J recombination, and the
      molecular mechanism of lymphoid neoplasia.

PMID- 12006989
TI  - [Effects of induced deletion of repeats in binding domain of the VLDL receptor on
      its ligand-binding capacity].
AB  - The ligand-binding domain of the very low-density lipoprotein receptor (VLDL-R)
      contains eight cysteine-rich repeat sequences that have been postulated as ligand
      binding sites. This is obviously different from that of low-density lipoprotein
      receptor (LDL-R) that includes seven similar repeats. To make clear the
      contribution of these repeats to ligand-binding and to explore the reason of both
      receptors' ligand-binding characteristic, the VLDL-R recombinants lacking
      different repeat(s) were constructed by oligonucleotide-directed mutagenesis and
      transfected into ldl-A7 cell. Ligand-binding results showed that repeat 1 and
      repeat 2 were the most important in binding with apoE-rich lipoprotein(VLDL and
      beta-VLDL). Repeat 3 and repeat 6 also important for binding VLDL. The results
      also showed that VLDL-R lacking LBR7 retained partly LDL-R ligand-binding
      properties. It suggests that LBR7 in VLDL-R may responsible for both receptors'
      ligand-binding properties differences.

PMID- 12006990
TI  - [Inhibitation of tumor angiogenesis, growth and metastasis by blocking VEGF
      paracrine pathway].
AB  - Solid tumors require an adequate vascular supply to grow beyond a certain
      dimension. It is known that formation of new blood vessels in tumor is mediated
      by unbalanced expression of angiogenic factors and their inhibitors. Among the
      former, the vascular endothelial growth factor (VEGF) has been assumed prime
      candidacy as a major positive physiological effector. To investigate the role of
      VEGF in angiogenesis associated with development of breast cancer, a sense VEGF
      and an anti-sense VEGF expression plasmids were constructed, and then were
      introduced into a human breast carcinoma cell line, MCF-7, expressing middle
      level of endogenous VEGF. Anti-sense VEGF(121) transfected MCF-7 cells that
      expressed reduced constitutive levels of VEGF and showed the same growing
      potential as untransfected MCF-7 cells in vitro, but it showed longer latency,
      smaller tumor, slower growth and prolonged survival time compared to parental or
      sense VEGF(165) transfected MCF-7 cells in vivo. Moreover, the tumors derived
      from anti-sense VEGF(121) transfected MCF-7 cells characterized by minimal
      vascularization and extensive necrosis. Finally, mice with primary subcutaneous
      tumors treated with intratumoral administration of anti-sense VEGF, or the
      plasmid expressing extracellular domain of the Flk-1 VEGF receptor (sFlk-1)
      followed by electroporation, showed significant tumor suppression. These results
      suggest that VEGF plays a major angiogenic role in breast cancer and a strategy,
      which blocks the VEGF paracrine pathway, may provide a means to control tumor
      growth topically without the risk of systemic antiangiogenesis.

PMID- 12006991
TI  - [Screening and identification of human lung cancer-related antigens].
AB  - One of the cardinal questions in tumor immunology is the identification of
      antigenic structures in human tumors that are recognized by host immune system. A
      powerful new methodology for identifying human tumor antigens eliciting humoral
      immune response is SEREX (serological identification of antigen by recombinant
      cDNA expression cloning). Here, by using this method, a recombinant cDNA
      expression library from lung cancer was analysed and several new tumor antigens
      were isolated. Using the lambda-ZAP vector, cDNA expression library was
      constructed from lung cancer tissues of three patients including a moderately
      differentiated lung adenocarcinoma, a highly differentiated lung squamous cell
      carcinoma and a moderately differentiated lung adeno-squamous carcinoma. The
      primary library consisted of 0.8 x 10(6) recombinants. 33 positive clones
      encoding antigen genes were obtained after immunoscreening, and the nucleotide
      sequences of cDNA inserts were determined and analysed with DNASIS and BLAST
      softwares in EMBL and GenBank. These antigen genes included known genes, such as
      MAGE (melanoma antigen gene), vitiligo-associated protein VIT-1, fibronectin, Na
      K-ATPase et al and unknown genes or ESTs. To characterize expression profile of
      these genes, antibodies in sera from 48 lung cancer patients and 48 health donors
      were assayed with three antigens (L-8, L-19, L-51) to screen specific and
      relative serum markers for lung cancer. The results show that positive rates in
      lung cancer patients are higher than in health donors. Our research indicates
      that some of these antigens may be related to lung cancer and may be valuable
      tumor markers in diagnosis of lung cancer.

PMID- 12006992
TI  - [hEPO transfer and expression by a recombinant adeno-associated virus vector].
AB  - In order to achieve sustained human erythropoietin (hEPO) expression in vivo for
      the treatment of anemias, recombinant adeno-associated virus (rAAV)-mediated hEPO
      transfer was studied in this report. rAAV vector plasmid carrying hEPO was
      constructed, and rAAV vector cell line for production of rAAV was also
      established. By using the   one helper virus-one vector cell line   strategy,
      which we reported previously, rAAV containing the hEPO expression cassette was
      produced in large-scale. The results showed that the hEPO expressed effectively
      by rAAV-mediated hEPO transfer into cultured BHK-21 cells. Intramuscular
      injection of rAAV-hEPO to Balb/c mice resulted in the in vivo expression of hEPO
      for at least ten weeks, along with the significant elevation of the hematocrits.
      This report indicates the potential use of rAAV-mediated gene transfer for the
      treatment of various anemias.

PMID- 12006993
TI  - [Cloning and expression of human calcyclin binding protein (hCacyBP) gene].
AB  - Human calcyclin binding protein (hCacyBP) gene was obtained by the screening of a
      human cDNA library. The full coding region of CacyBP was cloned into E.coli
      strain pET28, and then was expressed and purified through affinity
      chromatography. Rabbit anti-human CacyBP polyclonal antibody was obtained by
      immunizing rabbit with the purified human CacyBP. Western blots showed that it
      was expressed extensively in many tissues of mouse. The results of
      immunohistochemistrial staining showed that the location of CacyBP in BT325 cell
      line before and after differentiation changed from cytoplasm into nucleus and
      perinucleus cytoplasm.

PMID- 12006994
TI  - [Phosphorylation of YLR190w by PAP1 PHO85 kinase complex].
AB  - A yeast two-hybrid screening by using PAP1 was performed to identify targets for
      PAP1-PHO85 cyclin-CDK complex. N-terminal fragment of protein YLR190w, a yeast
      gene encoding a 491 amino acids peptide, was identified, and its coding region
      was amplified by PCR. The interaction of PAP1 and YLR190w was confirmed by both
      two-hybrid assay and GST pull-down assay in vitro. The PAP1-PHO85 kinase complex
      obtained from the immunoprecipitates could phosphorylate GST-YLR190w expressed in
      E.coli, and the phosphorylation of YLR190w was affected by the phosphate
      concentration, and the phosphorylation sites of YLR190w were Ser/Thr-Promotif, as
      revealed by protein mutation assay. In another library screen, YAF9, a yeast
      homolog of human AF9, was isolated using the two-hybrid system with YLR190w as
      the bait. It was revealed that interaction of YLR190w and YAF9 was affected by
      phosphate concentration. When all Ser/Thr in Ser/Thr-Pro motif were mutated to
      Ala, the interaction of YLR190w (mutant) and YAF9 was weakened, and the effect of
      phosphate concentration was impaired. Ylr190w was not involved in the PHO system
      by the acid phosphatase activity assay. Deletion of Ylr190w was constructed by
      homologous recombination and the doubling time of Ylr190w mutant strain as longer
      than that of wild type.

PMID- 12006995
TI  - [Changes of phenotypes associated with activated Src by overexpressed PTPalpha in
      NIH3T3 cells].
AB  - NIH3T3 cells transfected with inducible expression vectors harboring the protein
      tyrosine phosphatase alpha (PTPalpha) gene were used as a model to study the
      mechanism of tumor formation, by which the changes of phenotypes in inducible
      cells were studied. When NIH3T3 cells transfected with PTPalpha were induced for
      24 hours, the expression levels of PTPalpha in inducible cells was higher than
      those in uninducible cells as judged by RT-PCR and Western blotting; the
      expression level of Src in inducible cells was the same as those in uninducible
      cells, but activity of Src kinase in inducible cells was higher than those in
      uninducible cells.The level of phosphated tyrosine in Src was reduced in
      inducible cells. The malignant changes of phenotypes in the inducible cells were
      verified by flow cytometry and electron microscope. The results show that 24 h
      induction of PTPalpha could initiate the transformation of NIH3T3 cells
      transfected with PTPalpha inducible expression vectors, and the transformation
      may be associated with activated Src where pTyr(527) in the C tail was
      dephosphorylated by increased expression level of PTPalpha in the cells.

PMID- 12006996
TI  - [A novel bifunctional in vivo mutation detection system].
AB  - A shuttle plasmid pMCLacI/neo with two copies of LacI was integrated into mouse
      genome and a novel system which could detect in vivo mutation of both expression
      and silence genes was constructed, enabling the comparative analysis of their
      mutation spectra and mutant frequencies. 486 fertilized eggs from C57BL/6 mice
      with microinjected pMCLacI/neo plasmid were transferred into oviducts of 18
      pseudo-pregnant mice, and 32 alive offsprings were screened and identified by
      using PCR and Southern blotting. Genomes of 5 mice had pMCLacI/neo plasmid
      integrated, as verified by Southern blot after the PCR screening. Only one of the
      two LacI in pMCLacI/neo was in expression state; and this established a model,
      that the status in vivo of both gene expression and silencing could be simulated.
      This kind of mice might be used as a novel bifunctional mutation detection system
      in vivo.

PMID- 12006997
TI  - [Antiviral activity of a hammerhead ribozyme against HBV in HepG2.2.15 cells].
AB  - The carboxy terminal arginine  rich domain of core protein is highly conserved
      among HBV subtypes, and plays important roles in the packaging of pregenomic RNA
      and viral replication. Therefore, the 3' highly conserved region of HBV C gene is
      an attractive target for antiviral therapy mediated by ribozymes. A hammerhead
      ribozyme RzC, targeting the above site, was designed; meanwhile, as controls, the
      disabled form of RzC, dRzC, was also designed. In order to investigate its
      antiviral effects in cultured cells, in vitro-transcribed ribozymeRzC, dRzC and
      ribozyme expression vectors pCRzC, pCdRzC were delivered, respectively, into
      HepG2.2.15 cells ( clonal cells derived from HepG2 cells that contain integrated
      HBV ayw DNA). The preliminary results demonstrated that in vitro-transcribed
      ribozyme RzC had weak inhibition on HBV replication, possibly due to its quick
      degradation by RNases in cells, while the endogenously expressed ribozyme RzC
      showed significant inhibitory effect on HBV replication. In conclusion, the
      results suggested the possibility of the hammerhead ribozyme RzC to be used for
      the gene therapy of HBV infection.

PMID- 12006998
TI  - [Construction of a proteomic map database].
AB  - The first proteomic map database of China will be published by Bioinformation
      Center and Research Center of Proteomics, Shanghai Institutes for Biological
      Sciences, the Chinese Academy of Sciences.The database consists of physical
      layer, link layer and interfacial layer. As Java technique was introduced to
      construct the database system, the database does not depend on special working
      platform. With the search instruments users can easily look through the proteomic
      map and get concrete information of proteins they are interested in.

PMID- 12006999
TI  - [Preparation, characterization and receptor-binding capacity of pig serum
      transferrin half-molecules containing a single iron-binding site].
AB  - N- and C-half molecules containing a single iron-binding site were simultaneously
      obtained from trypsin digest of iron-saturated pig transferrin. The activities of
      the pig serum transferrin and of its N- and C-half molecules to bind the human
      placental membrane transferrin receptor were compared. The results indicate that
      the receptor-binding site of pig transferrin may be located at the C-half
      molecule of the transferrin.

PMID- 12007000
TI  - [Translational frameshift may be occur in p11, an interaction protein of Cx31, in
      yeast].
AB  - Connexin 31 is a member of connexin family. The carboxy-terminal cytosolic domain
      of connexin 31 contains several potential phosphorylation sites. In this work, a
      yeast two-hybrid protein interaction screen have been used to identify proteins
      that bind to the carboxy-terminus of connexin 31, and the p11 protein, an unique
      member of S100 protein family, and one of the two subunits of the annexin II
      tetramer was isolated. Interestingly, from yeast two-hybrid AD's coding sequence,
      three different reading frames of p11 DNA sequence were found,which come from
      different AD plasmids. By constructing AD plasmids using p11 ORF or 5' UTR, the
      protein coding by p11 ORF bind to connexin 31, while polypeptides coding by three
      kinds of 5 UTR did not bind to connexin 31, suggesting a translational frameshift
      of p11 fusion protein. To construct baits by dividing connexin 31 C-terminus into
      two domain, the p11 binding domain of connexin 31 was found located between 206
      237 codons. The plasmid Cx31CT-pGEX-4T-2 was constructed for expression and
      purification of GST-Cx31CT; and p11-pQE30 for expression and purification of
      6xHis-p11. In vitro binding assay showed that recombinant Cx31 interacted with
      recombinant p11.

PMID- 12007001
TI  - [Isolation and characterization of a novel transcript of hepatopoietin].
AB  - A novel transcript of human HPO (HPO-205) encoding a 205 amino acid ORF
      corresponding to a translated product of 23 kD different from the previous HPO
      that lacks the N-terminal 80 amino acids, was isolated from human fetal liver
      cDNA library by 5'RACE methods. The dose-dependent stimulation of DNA synthesis
      of HepG2 hepatoma cells by HPO-205 demonstrated its similar biological activity
      with HPO in vitro. The level of MAPK (mitogen-activated protein
      kinase)phosphorylation was further examined by Western blot analysis and the
      result revealed that HPO-205 protein might have stronger activity on stimulating
      hepatic cell proliferation than that of HPO. The similar result was observed by
      FACS technique. Therefore, our results suggest that the HPO-205 has activity to
      stimulate proliferation of liver derived cells, and this activity may be stronger
      than HPO.

PMID- 12007002
TI  - [Interaction between HTLV-1 transcription activator tax and Taxreb107].
AB  - Tax is a transcription activator encoded by human T-cell leukemia virus (HTLV)-1.
      Ribosomal protein L6 was also defined as Taxreb107 (Tax responsible element
      binding protein 107) for its activity of binding to the long terminal repeats of
      HTLV-1. To investigate the relationship between Tax and Taxreb107/RpL6, yeast two
      hybrid and GST pull-down assays were used. Results suggest that Tax can interact
      with Taxreb107/RpL6 directly and Taxreb107/RpL6 may regulate the function of Tax
      in HTLV-1 proliferation.

PMID- 12007003
TI  - [Gene expression pattern of senescence associated genes in rat muscle].
AB  - This work is aimed at the investigation of the senescence associated genes
      differentially expressed in rat muscle by cDNA microarray. After total RNA
      isolation, mRNA purification and probe preparation, the gene expression patterns
      of rat muscle from the old group (30 months old) and the young group (3 months
      old) were compared by cDNA gene chips. In the muscle of old rats there were
      reproducibly 127 differentially expressed genes, among which some down-regulated
      genes were involved in energy metabolism and signal transduction, while some up
      regulated genes were related to protein degradation and cell apoptosis. Meanwhile
      muscle fiber atrophy with mitochondria vacuolation was found in aging rat by
      electron microscope.

PMID- 12007004
TI  - [Effects of lead and selenium on telomere binding protein Rap1p, telomerase and
      telomeric DNA in Saccharomyces cerevisiae].
AB  - The effects on S.cerevisiae telomere binding protein Rap1p, telomerase and
      telomeric DNA by the lead (Pb), the selenium (Se) and Pb + Se were tested
      respectively in this study. Compared with the control S.cerevisiae after 100 gene
      rations, the mean telomere length shortened, Rap1p concentration was
      significantly lower and the secondary structure of Rap1p was disturbed, the
      telomerase activity was reduced in Pb treated cells. In Se treated cells,
      telomere length was significantly longer, and telomerase activity expressed
      higher. The concentration and secondary structure of Rap1p were similar to that
      of the control. Further more, the viability of Pb treated cells were
      significantly reduced while cells undergone other three treatments were similar
      and normal. These results suggest that Pb could damage Rap1p, reduce telomerase
      activity, resulting in the telomer length shortening and cell death. On the other
      hand, Se could protect and repair the damage in Rap1p and telomere caused by Pb
      to some extent.

PMID- 12007005
TI  - [Quantification of metallothionein induced with selenium by using competitive
      ELISA].
AB  - Metallothionein induced by selenium was assayed with competitive ELISA. It was
      found that in control mice, the liver contained (2.47+/-0.90) microgram MT/g wet
      weight tissue, while the mice administered with ZnSO(4) contained (8.15+/-2.20)
      microgram MT/g wet weight liver tissue and the mice given with selenium malt
      contained (12.80+/-1.44) microgram MT/g wet weight liver. A significant
      difference was found between the control and the latter two groups (P<0.05,
      P<0.05). The MT content of selenium group was significantly higher than the zinc
      group. It is suggested that the selenium was more potent in induction of MT and
      was a stronger inducer than ZnSO(4) in its effective dose range, therefore
      selenium may be developed into a novel and safe MT inducer.

PMID- 12007006
TI  - [Functional di-domain of neuronal growth inhibitory factor].
AB  - Neuronal growth inhibitory factor (GIF), known also as metallothionein-III (MT
      III), was the first validated to be capable of inhibiting growth of neuronal
      cells in nervous system, its beta-domain being functional. GIF functional di
      domain (GIFbeta- beta) was constructed to study the structure and function of
      GIF. N terminal beta-domain and C terminal beta-domain cDNAs were amplified by
      PCR, inserted into vector pGEX-4T-1 and expressed in Escherichia coli, as
      carboxyl terminal extension of glutathione-S-transferase (GST), by IPTG
      induction. After digestion by thrombin, the fusion protein was isolated by
      passing through a glutathione-Sepharose 4B affinity chromatography column and was
      purified by gel fit ration on Sephacryl-S100. About 60 mg protein per liter of
      bacterial cell culture was achieved. The results of SDS-PAGE, amino acid
      composition, molecular mass, the ratio of metal/protein and sulfhydryl
      group/protein showed that the purified protein was the GIFbeta- beta. Circular
      dichroism (CD) spectroscopy show GIFbeta- beta has characteristic metal
      sulfhydryl clusters of metallothionein family. Inhibitory activities detected by
      the MTT reduction assay are: GIF > GIFbeta-beta > GIF beta-domain.

PMID- 12007007
TI  - [Lab-on-a-chip (microfluidics) technology].
AB  - Over the last decade, the lab-on-a-chip concept has received considerable
      attention. This technology promises significant advantages in terms of speed,
      cost, sample/reagent consumption, contamination, efficiency and automation. In
      this review, we focus on lab-on-a-chip with fluid flow along micro-scale channels
      (microfluidics) and its application on life science and biotechnology.

PMID- 12007008
TI  - [Advances in fish antifreeze protein research].
AB  - Antifreeze proteins (AFPs) can highly effectively protect cells and embryos from
      damages in freezing process by lowering the freezing points of their cytoplasmic
      matrix and body fluids in a noncolligative manner. Based on their origins and
      properties, AFPs have been classified into four types, i.e. type I, II, III and
      IV. Each of them possesses rather distinct characteristics both in structure and
      composition, although all of them have ability of lowering freezing points of
      fluids. AFPs' genes have been characterized as members of a multigene family and
      the levels of their mRNA synthesis vary significantly with seasons. Adsorption
      inhibition operating at the ice surface is nowadays a hypothesis widely used to
      interpret the molecular mechanisms of noncolligative lowering of the freezing
      point, but the details of the mechanism on how the different types of AFP are
      adsorbed onto ice remain uncertain. Progresses in research on structures, amino
      acid compositions, genes, antifreeze mechanisms of the 4 distinct types of AFPs,
      and the application of the AFPs in cryopreservation of cells and embryos are
      reviewed here.

PMID- 12007009
TI  - The effect of N-terminal changes on arginyl-tRNA synthetase from Escherichia
      coli.
AB  - An Asn(2) deleted mutant of Escherichia coli arginyl-tRNA synthetase deleted
      Asn(2) and a chimera mutant, in which the N-terminal 23 amino acid residues of
      yeast arginyl-tRNA synthetase were appended to the N-terminus of Escherichia coli
      synthetase, were synthesized and studied. The expression of the deletion and
      chimera mutants in Escherichia coli formed inclusion bodies, presumably due to
      improper folding of the proteins. Relative to the native enzyme, the deletion
      mutant showed full amino acid activation activity and a 26% reduction in
      aminoacylation activity, while the chimera mutant lost 93% and 96% activities in
      aminoacid activation and aminoacylation, respectively, and did not aminoacylate
      yeast tRNA(Arg) at all. The mutant deleted Asn(2) and Ile(3) was able to be
      expressed in Escherichia coli but not stable to be purified. The emission maximum
      wavelength in the fluorescence spectra of the chimera mutants shifted to longer
      one and the corresponding intensities decreased, when compared with those of the
      native enzyme. The data show that the conformation of the mutants are different
      and the tryptophan residues in the mutants are more exposed than those in the
      native enzyme. An estimate of the secondary structure of the mutant enzymes from
      their far ultraviolet CD spectra showed that the chimera mutant contained less
      alpha-helix, more beta-sheet and slightly higher fraction of random coil, as
      compared with the native enzyme. The results indicate that an intact N-terminal
      domain of E.coli arginyl-tRNA synthetase is important to its activity and correct
      folding.

PMID- 12007010
TI  - Mouse restin inhibits bovine aortic endothelial cell proliferation and causes
      cell apoptosis.
AB  - Restin, a homologous protein of endostatin, was found by Ramchandran et al. It
      was the C-terminal fragment of type XV collagen. To analysis the inhibition
      activity of mouse restin on the proliferation of endothelial cells, the cDNA of
      restin was amplified from the total RNA of the mouse muscle and cloned into the
      prokaryotic expression plasmid pQE32. The recombinant protein was expressed in
      inclusion body with a yield about 60%--70% of total protein. After refolding, the
      purified recombinant protein specifically inhibits bovine aortic endothelial
      (BAE) cell proliferation stimulated by basic fibroblast growth factor (bFGF) in a
      dose-dependent manner, but the activity of restin was weaker than that of
      endostatin. Treatment of BAE cell with recombinant restin caused G(1) arrest and
      apoptosis in BAE cells.

PMID- 12007011
TI  - Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging.
AB  - Psoriasis, acne vulgaris and photoaging are common conditions. Tazarotene is a
      pro-drug of tazarotenic acid, a receptor-selective retinoid, which has shown
      efficacy in the treatment of these disorders. In the treatment of acne vulgaris,
      it has greater comedolytic activity than the currently available topical
      retinoids. In psoriasis, tazarotene normalizes keratinocyte differentiation,
      reverses keratinocyte hyperproliferation and has better anti-inflammatory effects
      than any of the currently available topical retinoids. It is most commonly used
      as combination therapy with a topical corticosteroid or phototherapy in
      psoriasis, or with an antibiotic in acne.

PMID- 12007012
TI  - Common sense dermatological drug suggestions for women who are breast-feeding.
AB  - Use of medications by breast-feeding mothers is not uncommon. When prescribing a
      medication to a nursing mother, the physician must weigh the potential risk of
      exposing the infant to the medication or the risks of not breast-feeding against
      the benefits of the medication to the mother. Information regarding the safety of
      common dermatological medications during lactation will be reviewed. Based on
      this information, treatment recommendations will be made.

PMID- 12007013
TI  - Alternative treatments for atopic dermatitis: a selected review.
AB  - Atopic dermatitis (AD) is a chronic itchy, inflammatory skin disease that is
      extremely difficult to treat. Effective therapeutic agents are limited in number,
      and may have long-term toxic side-effects. Frustrated by these realities, many
      patients stop seeking help from conventional physicians and turn to alternative
      medical approaches. These can include so-called natural products, herbal products
      and over-the-counter (OTC) treatments. Herbs and medications share a common
      history, as most of our well-known medications were derived from plants. However,
      herbal remedies are largely unregulated. Many may have scientific merit and
      clinical benefit, but they are still scientifically invalid and inadequately
      monitored. Dermatologists need information about the effects of herbal remedies
      in order to better serve their patients.

PMID- 12007014
TI  - Drug treatments for skin disease introduced in 2001.

PMID- 12007016
TI  - Enteric nervous system: development and developmental disturbances--part 1.
AB  - This review, which is presented in two parts, summarizes and synthesizes current
      views on the genetic, molecular, and cell biological underpinnings of the early
      embryonic phases of enteric nervous system (ENS) formation and its defects. In
      the first part, we describe the critical features of two principal abnormalities
      of ENS development: Hirschsprung's disease (HSCR) and intestinal neuronal
      dysplasia type B (INDB) in humans, and the similar abnormalities in animals.
      These represent the extremes of the diagnostic spectrum: HSCR has agreed and
      unequivocal diagnostic criteria, whereas the diagnosis and even existence of INDB
      as a clinical entity is highly controversial. The difficulties in diagnosis and
      treatment of both these conditions are discussed. We then review the genes now
      known which, when mutated or deleted, may cause defects of ENS development. Many
      of these genetic abnormalities in animal models give a phenotype similar or
      identical to HSCR, and were discovered by studies of humans and of mouse mutants
      with similar defects. The most important of these genes are those coding for
      molecules in the GDNF intercellular signaling system, and those coding for
      molecules in the ET-3 signaling system. However, a range of other genes for
      different signaling systems and for transcription factors also disturb ENS
      formation when they are deleted or mutated. In addition, a large proportion of
      HSCR cases have not been ascribed to the currently known genes, suggesting that
      additional genes for ENS development await discovery.

PMID- 12007017
TI  - Charles-Michel Billard (1800-1832): pioneer of infant pathology.

PMID- 12007018
TI  - Functional and gene expression analysis of the p53 signaling pathway in clear
      cell sarcoma of the kidney and congenital mesoblastic nephroma.
AB  - Mutation of p53 has been implicated in progression of classical Wilms tumor (WT)
      into the anaplastic variant (AWT), drug resistance, and poor prognosis. Because
      of prognostic similarities, clear cell sarcoma of the kidney (CCSK) has been
      classified with AWT and other aggressive pediatric renal tumors, apart from
      congenital mesoblastic nephroma (CMN), which is instead a relatively benign tumor
      of neonates. Initially, CCSK and CMN were assumed to be ontologically related,
      but the role of p53 in the pathogenesis of either disease has not been
      sufficiently evaluated as in AWT. We examined the status of p53 in CMN and CCSK
      in comparison to AWT by immunohistochemistry and mRNA analysis of p53, the
      downstream effector p21(WAF-1/CIP-1) ( p21), the multidrug resistance gene MDR-1,
      a putative target of p53, and the p53-antagonist Mdm-2. Surprisingly, strong p53
      nuclear immunoreactivity was found in cultures from two CMN specimens, but not in
      frozen or fixed tumor tissue from five other CMN specimens, nor in cell lines or
      tumor tissue from CCSK. Sequence analysis excluded p53 mutations. The size of the
      p53 mRNA in CMN and CCSK primary tumors excluded gross deletions or
      rearrangements. Low levels of Mdm-2 mRNA in CCSK and CMN primary tumors and
      cultures did not support a role for Mdm-2. Absence of MDR-1 mRNA excluded MDR-1
      in the drug-resistant phenotype of CCSK. Cisplatin-induced p21 transactivation
      assays and G(1) cell cycle arrest analyses showed that p21 transactivation and
      G(1) arrest occurred in both CCSK and CMN cultures, demonstrating integrity of
      the p53 signal transduction pathway. Absence of p53 functional abnormalities
      excluded relationships between CCSK and CMN as in AWT, supporting the association
      of cellular CMN with congenital fibrosarcomas as more recently proposed.

PMID- 12007019
TI  - Utility of WT1 as a reliable tool for the detection of minimal residual disease
      in children with leukemia.
AB  - WT1 encodes a transcription factor involved in the pathogenesis of Wilms' tumor.
      A high level of expression has been reported in blasts from patients with various
      hematological malignancies. The study was performed to evaluate the utility of
      monitoring WT1 expression in children with leukemia at diagnosis, during therapy,
      and following bone marrow transplant. We tested a total of 204 samples
      prospectively. These included samples from patients with the following diagnoses:
      acute lymphoblastic leukemia (ALL) at diagnosis (n = 45), at relapse (n = 14),
      and in remission (n = 45); acute non-lymphoblastic leukemia (ANLL) at diagnosis
      (n = 14), at relapse (n = 5), and in remission (n = 12); and chronic myelogenous
      leukemia (CML) in blast crisis (n = 1) and in chronic phase (n = 1). A total of
      33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition,
      samples from 5 patients with aplastic anemia and 28 controls were obtained from
      peripheral blood (n = 17), cord blood (n = 3), and bone marrow (n = 8). Primer
      pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT
      PCR was performed in all samples and compared with K562 cells from ATCC (defined
      as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562
      > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26
      ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1
      expression. In contrast, only 5 of 90 samples obtained in remission or post
      transplant showed high levels of WT1 expression ( P < 0.0001; 95% CI = 0.66
      0.94). The five patients with high WT1 expression during follow-up relapsed
      within 2 to 6 months. In conclusion, we have found that WT1 is consistently
      elevated in children with leukemia. Significant differences in the level of WT1
      expression were noted between these patients during diagnosis and at relapse, and
      those during remission. More importantly, following bone marrow transplant, a
      significant high level of WT1 expression preceded clinical relapse by 2 to 6
      months. Therefore, WT1 is a reliable marker for monitoring minimal residual
      disease during therapy as well as in the post-transplant period.

PMID- 12007020
TI  - Induction of drug resistance in human rhabdomyosarcoma cell lines is associated
      with increased maturation: possible explanation for differentiation in
      recurrences?
AB  - In rhabdomyosarcoma (RMS) of childhood and adolescence very little is known about
      interactions of cytotoxic drugs and tumor cells. In recurrent RMS the tumor cells
      are often more mature than in the primary tumor. The biological properties of
      these cells are still a subject of controversy. We investigated two human (RD2
      and TE 671) cell lines by cultivating them with doxorubicin, cisplatinum, and
      etoposide. Degree of differentiation and proliferation rate were estimated
      morphologically and by means of immunohistochemistry and a monolayer
      proliferation assay. Both morphological and immunohistochemical maturation was
      measurable in most resistant cell lines. An increase in myosin expression was
      most marked in the etoposide- and doxorubicin-resistant RD cell lines. The
      proliferation rate was decreased in almost all resistant cell lines.
      Nevertheless, the resistant cell lines tolerated high-dose levels of cytotoxic
      drugs at a higher proliferation rate than parental cell lines cultivated under
      similar conditions. The maturation seen in some recurrent tumors of RMS can be
      simulated in vitro by cultivating cell lines with cytotoxic drugs at sublethal
      doses. Interestingly, the resistance-associated induced maturation was not
      accompanied by p170 expression. After comparing these in vitro results with the
      maturation seen in RMS specimens after chemotherapy, we conclude that
      chemotherapy-induced differentiation in vivo might be a morphological sign of
      chemoresistance.

PMID- 12007021
TI  - Pulmonary hemangiomas of infancy and childhood: report of two cases and review of
      the literature.
AB  - Pulmonary hemangiomas are exceptionally rare in childhood and more so in infancy.
      They may involve the airways or the parenchyma, and may be localized or
      multifocal. We present two cases of pulmonary capillary hemangiomas. The first
      case is a localized form of capillary hemangioma that was resected from an 8-week
      old infant with signs of respiratory distress. A computed tomography scan showed
      a cystic mass initially thought to be an intrapulmonary bronchogenic cyst. A
      segmental resection was performed and examination revealed a localized capillary
      hemangioma without cystic or cavernous features. The second case is an example of
      a multifocal capillary hemangioma from a 9-year-old child who presented
      clinically with clubbing of fingers and toes and radiologically had multiple
      discrete nodules localized to the right lung. The clinical and pathological
      features of the cases are discussed together with a review of the literature. The
      distinction from other vascular neoplasms of childhood is briefly described.
      Although rare, pulmonary hemangiomas should be entertained in the diagnosis of
      both solid and cystic intrapulmonary lesions of childhood and infancy.

PMID- 12007022
TI  - Coexpression and accumulation of ubiquitin +1 and ZZ proteins in livers of
      children with alpha(1)-antitrypsin deficiency.
AB  - The ZZ variant of alpha(1)-antitrypsin deficiency (AATD) is well known to cause
      liver damage and cirrhosis in some affected children. Ubiquitin abnormality was
      recently shown to be significant in AATD in childhood cirrhosis. Molecular
      misreading (MM), defined as faulty transcription of genomic information from DNA
      into mRNA, as well as its translation into mutant proteins, has been documented
      in many pathologic processes where aggregation of abnormal proteins occurs. The
      misread protein, ubiquitin-B(+1) (UBB(+1)), was recently identified in the
      hallmarks of various neurological disorders. The objective of this study was to
      determine whether MM of ubiquitin occurs in AATD. Twelve explanted liver
      specimens from AATD-affected children with cirrhosis were retrieved from archival
      sources, along with 10 control liver specimens obtained from autopsies of age
      matched children with no clinical, gross anatomic, or histologic evidence of
      liver disease. Double immunofluorescence studies using rabbit polyclonal
      antibodies against UBB(+1) and AAT were performed on consecutively sectioned
      tissue. UBB(+1) immunoreactivity was colocalized with AAT in all cirrhotic AATD
      livers. The control livers were consistently negative. Ubiquitin MM is prominent
      in AATD-affected cirrhotic livers. This indicates that for children with AATD and
      cirrhosis, ubiquitin MM is a necessary cofactor to the aggregation of mutant ZZ
      isoform of AATD.

PMID- 12007023
TI  - Histologic features of the liver in type Ia glycogen storage disease: comparative
      study between different age groups and consecutive biopsies.
AB  - In this report, the histologic criteria for the diagnosis of type Ia glycogen
      storage disease (GSD) in a wide age range were studied. Liver needle biopsies of
      44 patients with type Ia GSD confirmed by enzyme analysis were re-evaluated and
      compared. Fatty change, nuclear hyperglycogenation (NH), and fibrosis were
      examined and graded. The second biopsies of 14 patients were also evaluated and
      compared with the first ones. The patients were grouped according to age: group
      I: <1 year (18 cases), group II: 1-5 years (19 cases), group III: >5 years (7
      cases). A mosaic pattern was detected in all biopsies. The amount of fibrosis in
      group I was less than that in the other two groups. The fatty change in group I
      was more prominent. There was not much difference in the amount of NH between age
      groups. In comparing the two different biopsies of 14 patients, the amount of
      fibrosis was found to be increased in 7 cases. NH was also increased in a
      different group of 7 patients. These findings were both statistically
      significant. The amount of fatty change was minimal in most of the cases.
      Fibrosis is associated with types III, IV, VI, IX, and X GSD. Our results support
      previous studies stating that fibrosis may also be present and varies in extent
      in type I GSD. Fatty change as large lipid vacuoles and NH may not be seen in
      many cases of type I GSD. Therefore, histologic criteria for the diagnosis of GSD
      may not be specific, and enzyme analysis should be performed.

PMID- 12007024
TI  - Annular elastolytic giant cell granuloma.
AB  - Annular elastolytic giant cell granuloma is a granulomatous process that presents
      as slowly growing annular papules and plaques on sun-exposed skin. It was first
      described in patients in the fourth and fifth decades of life. These lesions are
      primarily distributed on the head and neck. A review of the literature shows a
      preponderance of cases in adults. We report two cases of annular elastolytic
      giant cell granuloma developing in children under the age of 11 years.

PMID- 12007025
TI  - Rapid onset of severe twin-twin transfusion syndrome caused by placental venous
      thrombosis.
AB  - We report a case of rapid onset of severe twin-twin transfusion syndrome (TTTS)
      at 25 weeks gestation in a monochorionic twin pregnancy that was uneventful
      before that time. Thrombosis of a main venous branch draining several
      arteriovenous (AV) anastomoses to the donor changed the previous hemodynamic
      balance that existed between multiple bidirectional AV anastomoses. The opposing
      AVs became hemodynamically uncompensated and, despite amnioreductions, severe
      TTTS developed. At 27 weeks a cesarean section was performed because of worsening
      cardiotocography parameters of both fetuses. Birth weights were 750 and 1840 g,
      and initial hemoglobin concentrations were 9.2 and 13.4 mmol/liter for donor and
      recipient, respectively. The recipient twin died 5 months later of an ischemic,
      necrotic, and perforated small intestine due to a thrombosed superior mesenteric
      artery. The donor is well at 2.5 years. No abnormalities in several factors
      associated with thrombophilia, including factor V Leiden mutations, were found in
      the parents.

PMID- 12007026
TI  - Morphologic studies of the placenta and autopsy findings in neonatal-onset
      glutaric acidemia type II.
AB  - A case of neonatal-onset glutaric acidemia type II with electron-transfer
      flavoprotein (ETF) deficiency is presented. The morphological pattern of disease
      in the male infant included hypospadias, cryptorchidism, bilateral 13 ribs,
      nuclear cataract, cystic dysplasia of kidneys, lipid accumulation in the liver
      and renal tubular epithelium, and immature brain with white matter gliosis. The
      morphologic examination of the placenta revealed features of delayed maturation,
      including large-for-gestational-age size and abundant immature intermediate villi
      with cellular syncytiotrophoblast, persistent villous cytotrophoblast, and
      decreased syncytial knots. In addition, immature intermediate villi showed
      exaggeration of lacunar interstitial spaces consistent with non-hydropic villous
      edema. Marked lipid accumulation was seen within extravillous trophoblasts of
      placental septa and cell islands. Light lipid accumulation was also noted within
      fibroblasts of stem villi. These findings suggest that in glutaric acidemia type
      II, fatty acid oxidation could also be affected in the placenta.

PMID- 12007029
TI  - [Trend towards outpatient rehabilitation].

PMID- 12007030
TI  - [Expanding outpatient rehabilitation].
AB  - Up to now, the majority of rehabilitative measures in Germany has been performed
      in inpatient programmes. In the past 10 years an extension of outpatient
      rehabilitation can be noted. Because of new social welfare legislation the legal
      disadvantages for participants in outpatient rehabilitation have been eliminated
      on the 1st July 2001. In the past year, the Federal Rehabilitation Council as
      well as various rehabilitation providers have developed further and specified
      their concepts in outpatient rehabilitation. Concept requirements include still
      the principles of holism, interdisciplinarity, goal-oriented rehabilitation and
      team-work of rehabilitation staff. The extension of outpatient rehabilitation in
      the sphere of German pension insurance scheme is documented by the increase in
      models respectively regular services and rehabilitative measures. The results of
      the evaluation suggest, that the outpatient realisation of a comprehensive
      rehabilitation concept yields comparable results as the inpatient realisation. In
      some regions there is a strong cooperation between pension insurance institutes
      and corresponding health insurance companies in order to extend outpatient
      rehabilitation. A quality assurance program for outpatient rehabilitation will be
      developed. It can be expected, that the extension of outpatient rehabilitation
      goes on and that thereby the possibilities of a more flexible medical
      rehabilitation grow.

PMID- 12007031
TI  - [Perspectives of outpatient rehabilitation in Germany--brief report of an
      international symposium, December 2001 in Hamburg].

PMID- 12007032
TI  - [Evaluation of outpatient rehabilitation: goals, conceptual framework and study
      design of a health and pension insurance joint research project].
AB  - In Germany the statutory health and pension insurance schemes are the main
      providers of medical rehabilitation, the majority of rehabilitation measures
      being given in an inpatient setting. Over the last few years, the health and
      pension insurance schemes have strengthened the extension of outpatient
      rehabilitation, and have funded a comprehensive evaluation study in this context.
      In this evaluation study outpatient rehabilitation in centres with different
      conceptual backgrounds is compared with inpatient rehabilitation in rehab
      clinics, indications considered being cardiology and orthopaedics. Overall, 14
      rehab centres and more than 2000 patients were included in the project. The
      patients were interviewed and medically examined before and after the measure. A
      follow-up was done after six and twelve months. In addition to the rehabilitants
      themselves, the rehab centre physicians as well as the office-practice physicians
      were interviewed about the outcome of the rehab measure. One year after
      rehabilitation, data were collected from the relevant health and pension
      insurance funds concerning the benefits the patients had received. Due to the
      study's non-experimental design, validity of the results is confined to
      rehabilitants participating on an outpatient basis and who had been found
      medically suited for this type of rehabilitation, were capable of travelling to
      the rehab centre on their own within less than 45 minutes and had voluntarily
      opted for the outpatient setting. The findings of the study show that outpatient
      rehabilitants' motivation and expectations differ from those found in inpatient
      rehabilitation. The health economics analysis performed is restricted to the
      costs involved in the rehabilitation measure as such as well as the health
      related benefits provided to the rehabilitants in the twelve-month study period.
      The issue of whether increasing outpatient rehab measures will lead to decreasing
      costs in the rehab system as a whole had not been considered in the framework of
      this project.

PMID- 12007033
TI  - [Outpatient and inpatient orthopaedic rehabilitation--results of a study
      comparing outcome and costs].
AB  - This article presents main results of a study comparing outcome and costs of
      various all-day outpatient and inpatient orthopaedic rehabilitation forms. The
      results were obtained within the scope of a comprehensive evaluation programme
      commissioned by the federation of health (VdAK) and pension insurance institutes
      (VDR). The purpose of this evaluation was to examine the quality of different
      types of various rehabilitation care. The outcome comparison comprises a
      longitudinal follow-up of various somatic, psychosocial und occupational
      reintegration parameters up to one year after rehabilitation as well as outcome
      assessments from the perspective of patients and physicians in rehabilitation
      centres and general practice. The costs are estimated on the basis of data from
      health and pension insurance funds. The results show extensive corresponding of
      results und assessments in the different forms of rehabilitation care for
      comparable patient groups. There are no indications of poorer care quality in
      outpatient rehabilitation, while economic analyses show better cost effectiveness
      in outpatient treatment by comparability of treatment, patients, and results.
      Results suggest that outpatient care, offered in the same quality as in the
      examined rehabilitation centres, is an alternative or complement to inpatient
      care at least for those patients, who can be treated in both the outpatient and
      inpatient setting.

PMID- 12007034
TI  - [Structural and procedural quality of different orthopaedic rehabilitation
      settings: A comparison].
AB  - In addition to outcome quality, the quality of structure and process is an
      essential parameter for health care. In the context of a study comparing the
      outcome and costs of inpatient and different outpatient rehabilitation settings,
      the structural and procedural quality of the participating rehabilitation
      facilities were examined as well. Data were collected using questionnaires,
      interviews, treatment plans and visitations of the rehabilitation facilities. The
      analyses show a great correspondence of structural and procedural quality between
      the different rehabilitation settings. Particularly the data gathered by
      questionnaires show few differences. Points of significant difference include the
      more extensive equipment and the more favorable personnel key with regard to
      physicians in the inpatient clinics and the outpatient settings within these
      clinics. The outpatient rehabilitation facilities outside of rehabilitation
      clinics are characterized by a stronger accentuation of functional therapy, in
      particular physiotherapy and sports therapy. Functional therapy is of greater
      importance in the self-concept of the outpatient rehabilitation facilities and is
      also applied there more often.

PMID- 12007035
TI  - [Subjective estimations of the treatment programmes offered in inpatient and
      outpatient orthopaedic rehabilitation].
AB  - The survey of psychosocial, somatic and economic outcomes is regarded as standard
      in establishing the effectiveness of various rehabilitative forms of medical
      care. Another important part is the patient's perspective for the subjective
      valuation of the entire measure or different facets of the rehabilitation
      measure. During a comparison of the effectiveness of different forms of care of
      orthopaedic rehabilitation (inpatient, outpatient in the hospital, outpatient)
      1176 patients were questioned in writing at 4 different time points. The results
      concerning the general measurement of the satisfaction with the rehabilitation
      measure showed a high level and a high acceptance in all forms of medical care at
      the end of and after the measure. The result relating to the selection of the
      correct hospital for the specific troubles of the patient was positive as well.
      This can also be stated for the patients' estimation of the contacts between the
      doctors and the physiotherapists. At the end of measure, all the patients in
      every form of care viewed these contacts as being helpful. The outpatient offers
      were viewed a bit better by the patients concerning the contacts to doctors and
      physiotherapists. The extent of the care specific to the different occupational
      groups was estimated by almost all patients of all forms as being just about
      right. Additionally, the course organization and the work of the administration
      had a good evaluation - with slight advantages for the inpatient forms.

PMID- 12007036
TI  - [Outcomes of cardiac rehabilitation treatment and cost-effectiveness relations--A
      comparison between inpatient and outpatient rehabilitation programmes].
AB  - Regarding the dominance of inpatient medical rehabilitation programmes efforts
      have emerged over the last few years to strengthen outpatient medical
      rehabilitation programmes in Germany. The goal of cardiac rehabilitation is the
      recovery of physical, psychic and social wellbeing in people with a severe heart
      condition. For this contribution the central outcomes of cardiac rehabilitation
      were compared between different rehabilitation programmes (inpatient and
      outpatient) and cost-effectiveness analyses were made. These results were
      obtained within the scope of an evaluation study commissioned by the statutory
      health and pension insurance agency. In summary, the different rehabilitation
      programmes can be regarded as comparable concerning effectiveness and costs
      following rehabilitation.

PMID- 12007037
TI  - [The quality of organization in cardiac rehabilitation--a comparison of inpatient
      and outpatient forms of service delivery].
AB  - Regarding the ongoing dispute on strengthening outpatient medical rehabilitation
      programmes, questions arise about the quality of different (organizational) forms
      of rehabilitation (inpatient and outpatient). The aim of this contribution is to
      draw a comparison between the structures and processes of inpatient and
      outpatient facilities for cardiac rehabilitation. Additional questions will be
      posed regarding the prerequisite factors for improving structures and processes
      in the quality assurance and management framework.

PMID- 12007038
TI  - [Continuity and the quality of medical care for the cardiac patient: cardiac
      rehabilitation and its interfaces to acute care (phase I) and the process of
      coming back (phase III)].
AB  - Cardiac rehabilitation plays a pivotal role in the care for cardiac patients. Yet
      without sufficient continuity in the care process, the good results achieved in
      the different stages of therapy and recovery may not last. The aim of this
      contribution is to highlight the interfaces of cardiac rehabilitation in regard
      of process continuity as an aspect of the quality of health care. The results
      show that continuity between the acute care unit and inpatient rehabilitation
      programmes (phase I - phase II) seems to be sufficient whereas integrating phases
      II and III may be open for optimizing.

PMID- 12007039
TI  - [Outpatient orthopaedic rehabilitation: treatment, outcomes and costs as compared
      to inpatient rehabilitation].
AB  - In a parallel design the study examined an outpatient rehabilitation model
      project for patients of the pension insurance scheme of Rhineland-Palatinate (LVA
      Rheinland-Pfalz). In 6 centers for the rehabilitation of musculoskeletal diseases
      patients were assessed at the beginning and at the end of rehabilitation as well
      as six and twelve months after discharge. In this article the final results
      concerning therapeutic measures as well as health-related and economic outcomes
      are presented. Not included are aspects of differential utilization and the
      perception of the rehabilitation by the clients, which will be published in a
      separate article. No large differences were found concerning participation in the
      various therapeutic measures. As measured by the main score and the sub
      dimensions of the IRES patient questionnaire, effects of the same magnitude were
      found for the parallelized samples. Equally, no differences in outcome quality
      were found concerning the great majority of medical parameters documented in a
      doctors' questionnaire, the rate of applications for pension, occupational status
      twelve months after rehabilitation, as well as the reduction of sick-leave. The
      economic evaluation was carried out only from the perspective of the pension
      insurance agency. Considerable differences were found in the net costs of
      rehabilitation: although there are no user charges for patients in outpatient
      rehabilitation, mean expenditure was about 970 EURO lower than in inpatient
      rehabilitation. The study findings demonstrate that the concept of
      interdisciplinary rehabilitation has been realized in the outpatient centers as
      well and that the centers have reached an effectiveness comparable to that of
      inpatient rehabilitation. At least those patients who actively choose the
      outpatient setting gain as much as patients in inpatient rehabilitation.

PMID- 12007040
TI  - [Prognosis of labour force participation after multidisciplinary outpatient and
      inpatient rehabilitation for chronic back pain].
AB  - In a one-year prospective study of patients participating in a multidisciplinary
      outpatient or inpatient rehabilitation program (OPR/IPR) for chronic back pain
      the following issues were investigated: (i) the frequency of low labour force
      participation (LFP), i. e., work loss due to the disease or total duration of
      sick leave (SL) of 6 weeks or more; (ii) prognostic indicators at the beginning
      of the rehabilitation program (T1) for low LFP after one year (T2); (iii) the
      significance of the type of rehabilitation IPR vs. OPR in relation to the
      identified prognostic indicators for LFP. A total of 413 patients participating
      in OPR (n = 299) or IPR (n = 114) for chronic back pain returned a postal
      questionnaire after one year. Low LFP was found in 30 % of all patients without
      significant differences between OPR (32 %) and IPR (25 %). Compared to the year
      before T1 the proportion of patients without SL between T1 and T2 increased from
      12 % to 48 % after OPR, from 15 % to 47 % after IPR, respectively. In
      multivariate logistic regression analyses adjusted for type of rehabilitation the
      following prognostic indicators of T1 for low LFP were identified (p </= 0,05):
      SL of 6 weeks or more in the year before T1 with an odds ratio (OR) of 11.1;
      intended termination of employment (OR = 3.2), household income of less than 3300
      DM per month (OR = 2.2); reduced social functioning (SF-36) (OR = 2.0). Regarding
      LFP no significance of the type of rehabilitation (IPR vs. OPR) was found in
      relation to the identified prognostic indicators or after adjustment for
      differences (i) in the characteristics of the patients at T1, and (ii) in the
      duration and number of single measures of the rehabilitation program.
      CONCLUSIONS: One year after IPR or OPR the rate of return to work is similar
      (about seven out of ten patients). The identified prognostic indicators may
      stimulate further research of the improvement of the rehabilitation processes. No
      evidence was found against the expansion of OPR.

PMID- 12007041
TI  - [Outpatient cardiological rehabilitation--acceptance and conditions related to
      choice of setting].
AB  - In view of the increasing demands for more co-operation and integration among
      health care providers and "uninterrupted" care delivery processes increasing
      attention is being paid to establishing the determinants of a more flexible form
      of rehabilitation setting. Interest is focused particularly on determining at
      what stages and under what conditions specific choices of rehabilitation setting
      are made. In 1838 patients admitted consecutively to a cardiological
      rehabilitation clinic, the study investigated how many patients opted for
      outpatient rehabilitation and what factors influenced the patients' choice of
      rehabilitation setting. A total of 165 (9 %) of the 1838 patients chose
      outpatient rehabilitation. Patients who prefer outpatient rehabilitation are
      mainly male, belong to a higher social class and are younger. Patients who choose
      inpatient treatment feel more restricted by their illness. This is also revealed
      in the difference in coping strategies employed. Patients who prefer the
      inpatient setting show a greater tendency towards rumination than outpatients. It
      is thus comprehensible that these patients hope to gain a greater distance from
      their day-to-day problems. The results indicate that patients' willingness to
      take advantage of outpatient forms of rehabilitation is moderated both by
      sociodemographic, psychosocial and disease-related variables as well as by
      context variables. It is embedded in the complex biopsychosocial conditions
      governing rehabilitation. One consequence for managing the introduction of more
      flexible modes of rehabilitation could be to avoid dirigistic and unidimensional
      control parameters. The results indicate that more flexible disease management
      cannot follow fixed rules, but rather that the planning of individual
      requirements should be taken into account.

PMID- 12007042
TI  - [Short term results of outpatient vs. inpatient rehabilitation after stroke].
AB  - Fifty stroke patients who had already regained basic ADL-functions were
      investigated at the beginning and end of either inpatient or outpatient
      rehabilitation of similar therapeutic intensity in the same institution. For
      geographic reasons, outpatient treatment could only be offered to a subgroup of
      patients. Neurological deficits, extended ADL-functions and quality of life (SF
      36) were assessed. Patients who chose outpatient rehabilitation exhibited milder
      neurological deficits and better ADL-function at onset. On average, outpatient
      rehabilitation took about 8 days more than inpatient treatment. Under
      rehabilitation, gains with respect to ADL-functions and the QoL-dimensions
      "physical role function" and "physical functional ability" were realized. The
      magnitude of changes did not depend on setting. A decrease in "general health
      perception" may be related to the inpatient treatment of patients who would have
      preferred an outpatient setting. Brief periods between stroke and onset of
      rehabilitation and longer duration of rehabilitation treatment were significantly
      associated with better outcome with respect to ADL-functions.

PMID- 12007043
TI  - [Outpatient and inpatient neurological rehabilitation--a follow-up comparison].
AB  - Since the mid-90s outpatient rehabilitation has been developed by public health
      insurance companies and pension funds. Outpatient rehabilitation is defined as
      comprehensive multidisciplinary and medically supervised service which in
      neurological rehabilitation mostly follows inpatient rehabilitation. In the
      present paper partial results of a larger study (by Schoenle and Leyhe, 2000) are
      reported with respect to the follow-up of the effects of outpatient versus
      inpatient rehabilitation 6 month after termination of the treatment. Major
      results are the endurance of the effects over the observed time interval and the
      equivalent effectiveness of the two forms of rehabilitation. Distinct effects
      were observed for the two patient groups (more progress in the body related
      functional disturbances for inpatients versus cognitively related progress for
      the outpatients). The results reflect intrinsic features of neurological
      rehabilitation and the current organizational status of neurological
      rehabilitation in Germany.

PMID- 12007044
TI  - [Rehabilitation outcomes of a psychosomatic clinic integrating fully inpatient
      and partial hospitalization rehabilitation approaches: a comparison].
AB  - As publications from the domain of psychosomatic rehabilitation pertaining to the
      conceptual approaches and effects of partial-hospitalization rehabilitation have
      so far relied on very small case numbers, the effectiveness of partial
      hospitalization rehabilitation was analysed in 318 patients in comparison to a
      large sample of rehabilitants who had participated in fully inpatient
      rehabilitation. No relevant differences were found among the groups studied in
      sociodemographic respects or range of diagnoses. The same was true concerning the
      level of complaints present at the onset of rehabilitation. Good rehabilitation
      outcomes were achieved in both groups, however, the effect sizes found for
      changes in depressiveness and indulgence to complaining ("Klagsamkeit") (GSI from
      the SCL-90) were lower in the partial-hospitalization group than in the patients
      in fully inpatient rehabilitation. Also, the relatively high share of partial
      hospitalization patients discharged unable to return to work might be clinically
      significant. While our findings confirm the good results reported from other
      disciplines, they nevertheless are a reminder of the need for very careful
      selection of patients for partial-hospitalization rehabilitation, in order not to
      withhold "better" rehabilitation than could be provided on a partial
      hospitalization basis from patients with special sociomedical problems. The best
      rehabilitation outcomes seem to be achieved by those patients who, towards the
      end of fully inpatient rehabilitation, were granted transition to the partial
      hospitalization programme.

PMID- 12007045
TI  - [Outpatient rehabilitation of alcohol dependent patients in a day clinic: initial
      results of a comparative follow-up study of day clinic and inpatient treatment].
AB  - This article describes the development of an outpatient concept for the day
      clinic withdrawal treatment of alcohol dependent persons in a Hamburg institution
      for addiction aid. It reports the initial, selected results of a comparative
      follow-up study of patients discharged during the years 1998-2000, who either
      receive ambulatory treatment in the day clinic (n = 270) or inpatient treatment
      in the institution's special clinic (n = 462). Assessable questionnaires are
      available from 131 outpatients of the day-clinic treatment and 173 patients of
      the inpatient treatment form. The response rate - with reference to the group of
      those who were reachable - was 57.2 % for patients of the day clinic and 53.2 %
      for patients of the special clinic. The results of the study arrive at the
      conclusion that both treatment forms can be seen as thoroughly comparable with
      regard to primary outcome measurements (for example reduction of psychological
      stress, abstinence rates, reintegration into occupational life). Rehabilitants
      treated in the inpatient setting more frequently report that they had already
      contacted centres for further treatment and self-help groups during the
      rehabilitation phase, which however doesn't lead to a change of participation
      behaviour following the rehabilitation phase. This serves to confirm the
      assumption that an additional offer of a day-clinic service in the area of
      addiction rehabilitation provides a further, effective treatment concept that
      sensibly supplements the otherwise inpatient-oriented treatment landscape. The
      results indicate the quality of the work performed in the day clinic studied (as
      well as in the inpatient clinic) and should encourage the funding agencies and
      employees of other day clinic institutions in the field of addiction
      rehabilitation to participate in evaluation and quality assurance measures, thus
      continuing to bridge the gap between the (theoretical) state of knowledge
      concerning outpatient rehabilitation and the degree to which it can be
      successfully realized.

PMID- 12007046
TI  - [Economic aspects of outpatient rehabilitation--methods and results of a study
      about economic efficiency of outpatient rehabilitation in Mecklenburg
      Vorpommern].
AB  - Since the recent changes in the German social code the outpatient rehabilitation
      system gains importance. While more and more studies investigate the medical
      outcomes of outpatient rehabilitation, the economic effects have hardly been
      examined so far. This article first presents fundamental methods to use for
      economic evaluation of outpatient rehabilitation and subsequently outlines the
      findings of a project comparing the economic effects of outpatient and inpatient
      rehabilitation in Mecklenburg-Vorpommern. The study statistically covers the
      total population of applicants for orthopaedic-traumatologic rehabilitation who
      are suitable for outpatient rehabilitation. A randomized and controlled study, it
      investigates outcome parameters of the two variants of rehabilitation compared.
      If the results are approximately equal, the differences between amounts and
      periods of payments and costs for the pension insurance agency are analyzed. And
      in fact, the results obtained so far from the investigation confirm that, in
      suitable patients, outpatient rehabilitation can achieve approximately the same
      outcomes as inpatient rehabilitation - but at distinctly lower costs. Although in
      the short term (i. e., at the end of treatment) outcome levels are somewhat
      lower, better results found even one year later however indicate a more sustained
      effect.

PMID- 12007047
TI  - [Quality assurance and quality management in medical rehabilitation--joint
      conference of the Thuringian Rehabilitation and Health Alliance and the German
      Society for Medical Rehabilitation, Oct. 10, 2001 in Erfurt].

PMID- 12007048
TI  - Role of the anterolateral thigh flap in head and neck reconstruction: advantages
      of moderate skin and subcutaneous thickness.
AB  - Skin-flap thickness is an important consideration when choosing a free flap for
      head and neck reconstruction. The anterolateral thigh flap, the rectus abdominis
      flap, and the radial forearm flap, which included the epidermis, the dermal, and
      the subcutaneous layers, were measured using ultrasonography in 31 patients. The
      mean skin and subcutaneous thickness of the anterolateral thigh flap was 7.1 mm;
      the rectus abdominis flap was 13.7 mm; and the radial forearm flap was 2.1 mm.
      Further analysis revealed a statistically significant difference among the skin
      and subcutaneous thickness of the three flap groups. Of the 44 anterolateral
      thigh flap transfers done for head and neck reconstruction after cancer ablative
      surgery, 41 (93.2 percent) were transferred successfully. The anterolateral thigh
      flap creates a moderately thick skin flap, and is less variable in thickness
      across its area than is the rectus abdominis flap. The flap is adaptable for
      reconstruction of head and neck soft-tissue defects.

PMID- 12007049
TI  - Vascularized medial sural cutaneous nerve based on the superficial sural artery:
      a reliable nerve graft.
AB  - The sural nerve is nourished by the single superficial sural artery proximally,
      but distally receives multiple contributions from musculocutaneous and
      fasciocutaneous perforators of the posterior tibial and peroneal (fibular)
      arteries. The prevalence of this proximal arterial supply is largely unknown. The
      authors report a large anatomic study (n = 56), together with two clinical cases,
      to assess the incidence and potential suitability of the sural nerve as a
      vascularized nerve graft. Dissections were performed on 6 fresh cadavers injected
      with Microfil dye and on 22 preserved cadavers. The superficial sural artery was
      present in 91 percent of the dissections. The mean diameter of this extrinsic
      artery was 1.5 mm. The mean percentage of neural tissue within the sural nerve in
      the region where it is supplied by the superficial sural artery was 62 percent
      compared to 34 percent distally, where it was supplied by the posterior tibial
      and fibular (peroneal) arteries. This anatomic difference provides a solid
      rationale for preferential utilization of the proximal portion of the nerve, as
      opposed to its distal segment. When a vascularized nerve graft is indicated, the
      proximally-based sural nerve appears to offer clear advantages, compared to other
      vascularized nerve grafts.

PMID- 12007051
TI  - "Extracorporeal loop" (blind loop): an alternative microsurgical technique for
      prelaminated flap transfer.
AB  - Free tissue transfer is frequently used for reconstruction in the head and neck
      region. In patients who suffer tissue loss due to a high-energy trauma, the
      reconstructive surgeon is often faced with a large gap between the defect and the
      site of anastomosis outside the zone of injury. Utilization of long vein grafts
      for reestablishment of blood flow to the transferred tissue vessels is a common
      procedure. Arteriovenous fistula (AVF) formation on the side table is an
      alternative solution. In this paper, an "extracorporeal loop" (blind loop)
      technique is presented as an alternative microsurgical method for prelaminated
      flap transfer to two different traumatic recipient areas in the face (nose and
      ear).

PMID- 12007053
TI  - Breast reconstruction with the free bipedicled inferior TRAM flap by anastomosis
      to the proximal and distal ends of the internal mammary vessels.
AB  - Breast reconstruction after traditional radical mastectomy is particularly
      challenging for the plastic surgeon. Not only the breast, but subclavian and
      anterior axillary-fold deformities need to be corrected. An entire TRAM flap
      (including zone IV) is required, and bipedicled deep inferior epigastric vessels
      are needed to insure that the entire flap will survive completely. However, on
      the chest, it is difficult to locate the two suitable sets of recipient vessels
      for the two pedicles. The thoracodorsal vessels have usually been damaged during
      axillary dissection or radiation therapy. In the past, the proximal ends of the
      internal mammary artery and vein (IMA, IMV) have been used as recipient vessels
      with free flaps, with ligation of the distal ends. These authors have used both
      the proximal and distal ends of the IMA and IMV as recipient vessels for end-to
      end anastomoses to the bipedicled deep inferior epigastric vessels (DIEA, DIEV)
      in seven clinical cases, with very satisfactory results obtained. Anatomic
      studies of the IMA and IMV were done in 10 dogs and two active patients,
      including studying hemodynamic changes at the proximal and distal ends of the
      IMA, and evaluation of perfusion units in the free bilateral TRAM flap. In the
      animal experiments, the mean pressure at the distal ends was 86/77 mmHg (left
      sides) and 87/78 mmHg (right sides); pressure was 63 to 71 percent of the
      proximal ends (p<0.05). There was no statistically significant difference between
      the pressures on the left and right sides. In the two patients, and in 5 others,
      the pressure at the distal ends was 66 and 58 mmHg, which was 75 to 77% of the
      pressure at the proximal ends. The blood flow at the two anastomotic stomas was
      similar in a 5-year follow-up. The clinical and experimental studies showed that
      the distal IMA has reduced perfusion pressure, but that it provides excellent
      flow and flap perfusion, allowing reliable use of two pedicles for survival of
      the entire flap.

PMID- 12007054
TI  - Manageable microsurgical technique for creating an opening in small vessels for
      end-to-side anastomosis.
AB  - The end-to-side anastomosis is one of the most useful techniques in microsurgery.
      It creates a recipient opening for the donor, keeps the donor vessel intact, and
      does not interrupt distal blood flow, compared to the end-to-end anastomosis
      technique. The end-to-side anastomosis is consequently becoming more acceptable
      in reconstructive microsurgery. The author describes a manageable microsurgical
      technique for creating recipient vessel openings in small vessels for end-to-side
      anastomoses.

PMID- 12007055
TI  - Muscle preservation by prolonged sensory protection.
AB  - The functional recovery of a muscle target following nerve repair is inversely
      related to the denervation time: i.e., the longer the muscle denervation, the
      poorer the functional outcome following nerve reconstruction. The trophic and
      protective effects of sensory innervation to a motor nerve, following prolonged
      denervation (greater than 6 months), have been studied. Following proximal
      transection of the musculocutaneous nerve (MC) close to its C6 origin in 10 adult
      male Sprague-Dawley rats, the severed nerve was coapted to supraclavicular purely
      sensory nerves originating from C3 and C4 (sensory protection [SP] group). In
      another 10 Sprague-Dawley rats, the transected MC nerve was not protected by
      coaptation to sensory nerves (control group). After prolonged denervation or
      "sensory protection" (6 months), the MC nerve was then coapted in both groups to
      the purely motor medial pectoral nerve. Behavioral testing (grooming test) was
      performed on a weekly basis during the reinnervation time, which lasted 4 weeks.
      Statistically significant differences (p<0.05) favoring the SP group, were found
      at the second week of the reinnervation period, but not at the end of the
      experiment. Evaluation also included intraoperative electrical stimulation of the
      MC nerve, biceps muscle dry weights, motor endplate counts, and nerve axon counts
      of the MC nerve. The biceps muscle dry weights were statistically higher in the
      SP group, along with a trend for a higher number of motor endplates. No
      statistically significant difference was found in the nerve axon counts of the MC
      nerve between the two groups. Statistically better intraoperative electrical
      stimulation results were also encountered in the sensory protection group. An
      interpretation of the results favors the hypothesis that sensory reinnervation of
      a motor target may provide the necessary trophic environment to minimize muscle
      atrophy, until a motor donor nerve becomes available.

PMID- 12007057
TI  - Combined method of free lateral leg perforator flap with cervicoplasty for
      reconstruction of anterior cervical scar contractures: a new flap.
AB  - Anterior cervical scar contracture remains a challenging problem for the plastic
      surgeon. Recent advances in flap techniques have made it possible to transfer
      various kinds of autogenous tissue. A free lateral leg perforator flap (LLPF) was
      first introduced and developed to reconstruct this burn deformity, according to
      the special nature of perforator anatomy. The authors used this flap to resurface
      post-burn anterior cervical contracture in a 31-year-old female patient with
      second-to-third-degree flame burns. The size of the excised scar was 25 x 5.5 cm;
      the size of the flap was 22 x 8 cm, with total flap survival. The hospital stay
      was 9 days, and the donor site was covered with a split-thickness skin graft.
      After a 5-month follow-up, functional improvement was evaluated by an increase in
      extension of 33 degrees (preoperative 92 to postoperative 125 degrees); an
      increase in rotation of 15 degrees (preoperative 70 to postoperative 85 degrees);
      and an increase in lateral flexion of 10 degrees (preoperative 35 to
      postoperative 45 degrees). The cervicomandibular angle was improved by 20 degrees
      (preoperative 110 degrees to postoperative 90 degrees). Both functional and
      aesthetic results, including contour restoration, can be achieved, using this
      kind of perforator flap combined with cervicoplasty.

PMID- 12007058
TI  - A modified method of microvascular autogenous interposition vein grafting for
      vascular reconstruction.
AB  - A modified technique of vein grafting for vascular reconstruction that
      facilitates surgical procedures by preventing size, diameter, and length
      discrepancies as well as twisting, is presented. The distal end of the harvested
      vein graft is ligated, and the graft is inflated with heparinzed saline. The
      determination of the small side branches makes ligation easier. Gentle
      hydrostatic dilation relieves spasm, straightens the vein, and ligation of the
      proximal end is then performed under tension. As the vein inflated with
      heparinzed saline achieves maximum size, diameter, and length without torsion,
      the sausage-like graft can easily be interposed in tunnels, passages, or soft
      tissues between recipient vessel gaps. As the graft is under adequate tension, it
      is easy to determine its appropriate length, size, and diameter. Suturing is
      carried out using double approximating clamps. The graft will not twist or kink,
      as it is anastomosed under tension. The clamps are left in place until completion
      of the distal and proximal anastomoses. The distal clamp is released first. With
      this simple modification, most of the technical difficulties, such as length,
      size, and diameter discrepancies, and twisting and torsion of the graft, can be
      eliminated. The risk of failure due to vascular thrombosis at the anastomotic
      sites is lowered, as the vein graft is filled with heparinzed saline, and no
      blood flow is permitted during the reconstruction. The surgeon also saves time
      with this easy, simple, and feasible method.

PMID- 12007059
TI  - On "Pre-, intra-, and postoperative electrophysiologic analysis of the recovery
      of old injuries of the peripheral nerve and brachial plexus after microsurgical
      management" (Journal of Reconstructive Microsurgery 2002;18:77-82).

PMID- 12007060
TI  - On effects of ketamine to axillary block in hand surgery.

PMID- 12007064
TI  - [Effects of a regional intervention to promote asthma guidelines implementation].
AB  - AIM: Despite of asthma guidelines existing for years, secondary data analysis
      shows insufficient medical care of asthmatics in Germany. The aim of the present
      study was to improve asthma guideline adherence by promoting guidelines
      implementation. METHOD: We analyzed prospectively pre- and post-interventional
      medical care of a sample of 127 asthmatics who were recruited by physicians
      working in ambulatory care and in hospitals of the Region Neckar-Alb, Germany.
      Data came primarily from patient interviews by phone. Our intervention to promote
      guidelines implementation consisted of following methods: 1. analyzing regional
      asthma care followed by a feedback performance report to physicians; 2.
      delivering asthma patient diaries and peak flow meters to study patients; 3.
      developing and adapting regionally asthma guidelines for adult asthmatics in the
      Region of Neckar-Alb; 4. promoting guidelines utilization by publishing the
      adapted guidelines in a scientific journal, direct mailing of a short version to
      the practitioners, and boosting the guidelines at regional CE meetings; 5.
      reanalyzing asthma care of the study cohort and the implementation of the
      guidelines 13 months after the beginning of the intervention. We studied the
      effect of the intervention using a qualitative model comprising 18 quality
      indicators measuring the proportion of patients who were treated in accordance to
      the guidelines. To compare pre- and post-interventional proportions we used the
      McNemar test for statistical analysis. RESULTS: The proportion of asthmatics
      treated in accordance to the guidelines improved significantly from 48 % to 57 %.
      The increase was mainly due to an improvement of guidelines adherence within the
      field of promoting asthma self-management and continuous monitoring of patients
      (42 % pre- and 57 % post-intervention), whereas guidelines adherence in
      pharmacotherapy improved only from 53 % to 56 %. CONCLUSION: The proportion of
      asthmatics treated in accordance to guidelines can be improved by using a
      multifaceted regional approach to promote guidelines implementation.

PMID- 12007065
TI  - [DRGs of musculoskeletal diseases: consequences for orthopaedics and accident
      surgery].
AB  - The introduction of the new prospective payment system for inpatient care entails
      considerable changes for hospitals in Germany. The Australian Refined Diagnosis
      Related Groups (AR-DRGs), which form the basis for the German system, give the
      chance to estimate the consequences and implications for the specialty of
      orthopaedic surgery in Germany. Our study aims at highlighting the most important
      musculoskeletal diagnoses and to provide an initial economic forecast for them.
      The comparison with Australian data gives hints for operative and conservative
      rehabilitative orthopaedic departments in respect to potentials and focal points
      for the development of novel patient management tools. The success of orthopaedic
      departments will depend in the future much more than now on organisational and
      management issues.

PMID- 12007066
TI  - [Possibilities of utilising official statistics for health services research].
AB  - This report deals with the experiences and problems with using official
      statistics on a limited area level of Germany's 440 administrative districts. The
      data comprised health-related issues and were used for an ecological analysis of
      the determinants of hospital use. We obtained health statistics data from
      homepages of the German health report, the Federal statistics office, and the 16
      statistics offices of the Federal states. We also made use of the data base of
      the joint regional statistics published by the Federal and regional statistics
      offices. Finally, there was a co-ordinated inquiry to the regional statistics
      offices about the supply of data on mortality, hospital discharges, structure of
      hospital care and several socio-economic indicators. The process of data
      collecting was mostly unproblematic. On the other hand, not all of the data were
      available on a limited area level in a satisfying form and quality. For reasons
      of data protection some information of small districts was transmitted
      incompletely. Additionally, there are procedural differences between regional
      statistics offices regarding the differentiation between some variables and in
      the exchange of data between the federal states. Finally, some problems were due
      to varying age classifications for different health indicators. For health
      services research the use of official statistics becomes increasingly comfortable
      via health reports and Internet. However, for specific questions of research some
      problems still remain, rising from missing standardised health indicators and
      deficient availability of limited area health data. Data collection is
      exacerbated by restrictive interpretation of data protection acts and the
      different handling of data inquiries in the regional statistics offices. Finally,
      there is a lack of data on morbidity and use of ambulatory care.

PMID- 12007067
TI  - [Needle stick injuries in health care - frequency, causes und preventive
      strategies].
AB  - Healthcare workers (HCW) are at risk for infections with blood-borne pathogens -
      especially hepatitis B virus (HBV), hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV) - resulting from occupational blood-exposure trough
      injuries with sharp instruments and needle sticks. Results of a study on the
      epidemiology of needle stick injuries (NSI) among HCW in two German hospitals
      indicate that 500,000 NSI occur annually in Germany. Most of these injuries occur
      during disposal of used syringes and "recapping". Administration of the post
      exposure prophylaxis is recommended for HCW who are occupationally exposed to HBV
      (vaccine/immunoglobulin) and HIV (antiretroviral drugs) i.e. the immediately
      reporting of blood exposure is very important. Comprehensive programmes to
      prevent NSI - e.g. avoiding of recapping, use of disposal containers, surgical
      gloves and in particular safety devices - minimize a high cost of NSI due to the
      administration of PEP, developing of chronic hepatitis, cirrhosis and liver
      cancer.

PMID- 12007068
TI  - [Free choice of doctors - an international comparison].
AB  - The focus of this international comparison concerning the issue of free choice
      among primary care physicians and specialists is to learn from experiences in
      other countries. Two different types of health care systems are analysed: state
      administered health systems such as in Finland and Great Britain or competition
      based systems such as in Switzerland and the USA. In the countries outlined
      mentioned and other OECD nations (Organisation for Economic Co-Operation and
      Development) not described in this study, several restrictions of free choice
      among physicians can be observed. Restrictions are to be found when changing the
      general practitioner as well as in first contact to specialists. Both limitations
      do not seem to have a significant effect on the level of satisfaction of the
      population with health care in general. From an international perspective free
      choice of doctors seems to be an exception in health systems.

PMID- 12007069
TI  - [Development of legislation for the care of the mentally ill as seen by the
      psychiatrist].
AB  - Ten years after the introduction of the new legislation concerning mentally ill
      or impaired persons ("Betreuungsrecht") it is now possible to review the
      problems. These cover inter alia the appointment of a curator to the legal
      proceedings, the practice of the reservation of consent, the question of legal
      incapacity and the cost problem. The medical expert must be aware of the
      development of these issues, especially as the medical and the juridical point of
      view often do not correspond with the well-being of the patient. This article
      conveys views from the psychiatric perspective to the questions outlined above
      and offers suggestions for possible improvements.

PMID- 12007070
TI  - [Light, melatonin and internal cancers - recent facts and research perspectives].
AB  - Visible light of sufficient intensity inhibits melatonin biosynthesis and
      numerous experimental studies suggest that melatonin may protect against cancer.
      From a public health point of view it is important to verify or falsify the
      hypothesis that artificial light - or even sunlight itself - suppresses melatonin
      production sufficiently to increase the risk of developing cancers of internal
      organs. Since humans are exposed universally, even small risk elevations could
      lead to numerous cases. Recent epidemiological studies of people exposed to
      anthropogenic light-at-night in the course of shift work and first evaluations of
      natural light experiments in blind people and in residents of the Arctic are
      compatible with the possibility that light can influence - at least hormone-
      dependent - cancer developments via melatonin. To systematically investigate the
      effect of geographically different light intensities on melatonin production in
      man, a pan-European study is suggested. Further epidemiological investigations
      can contribute to the understanding of the patho-physiological relationships
      between light, melatonin and human biology.

PMID- 12007071
TI  - [Gender-sensitive public health publications in Germany? Results of a review of
      literature].
AB  - BACKGROUND: The project 'Gender Bias - Gender Research' investigates how far
      gender issues are considered in German-language Public Health journals. Target is
      the analysis of the publication practice in Public Health in order to point out
      status, deficits and perspectives of gender-specific research. METHODS: We
      developed a standardised evaluation instrument, which covers the semantic,
      methodical-technical and contentual area regarding gender issues and evaluated
      all original contributions of the years 1990, 1995 and 1999 in the journals 'Das
      Gesundheitswesen', 'Sozial- und Praventivmedizin' and 'Zeitschrift fur
      Gesundheitswissenschaften'. 268 (of 517) contributions applied to persons (in
      contrast to i. e. programmes, institutions) and were completely analysed.
      RESULTS: The main part of the contributions take women and men into account, but
      do not consider them continuously in all parts of the research process and in
      this way do not fulfil all requirements for gender-sensitive research. Gender
      finds most consideration on the semantic level. Less than half of the authors
      consider the different situation of women and men in the formulation in
      hypotheses, sampling, or data analysis, and only 35 % of them make reference to
      this in their conclusions. We found differences between the examined journals and
      years. CONCLUSIONS: The concerns of women and men should be considered at all
      levels of research. Attention should be paid to this when writing, reviewing and
      publishing contributions.

PMID- 12007073
TI  - [The "AMDP-rating scale for obsessive-compulsive symptoms": The 2nd version].
AB  - The "Association of Methodology and Documentation in Psychiatry" (AMDP) has
      developed the 2nd version of a new observer-rated scale for a quick and precise
      assessment of obsessive-compulsive symptoms. The first version of the scale
      comprised 20 items on the dimensions "description", "distress and impairment" and
      "emotion and cognition". The item pool of the 2. version was enlarged to 44 items
      to accomplish a differentiated assessment of obsessions and compulsions and to
      assess the associated passive avoidance behaviour. The results of an empirical
      study (n = 141) demonstrated excellent internal consistency (Cronbach's alpha =
      0,93), a split-half reliability of 0,83 (Spearman-Brown), a test-retest
      reliability of r = 0,84, a high interrater-reliability, a high differential
      validity and good convergent validity with the Hamburger Zwangsinventar (HZI) and
      the SCL-90-R. The results are presented and their implications on the final steps
      of the development of the scale will be discussed.

PMID- 12007074
TI  - [Atypical antipsychotics in the treatment of bipolar affective disorders].
AB  - Antipsychotics are commonly used in the treatment of bipolar affective disorder.
      The use of conventional antipsychotic agents, though effective as antimanic
      agents, is associated with a number of limitations such as their acute side
      effect profile and their unsufficient mood stabilizing activity. In addition,
      exposure to conventional neuroleptics poses a risk for the development of tardive
      dyskinesia, especially in mood disorder patients. Growing evidence suggests that
      the novel, so-called atypical neuroleptics may offer a number of advantages in
      the treatment of bipolar disorder, including their thymoleptic activity and
      minimal risk for acute and long-term extraypyramidal symptoms. Clinical
      experience with clozapine and olanzapine as mood stabilizers suggests greater
      antimanic than antidepressant properties, while risperidone may have greater
      antidepressant properties with some liability for triggering or exacerbating
      mania. The mood stabilizing properties of further atypical drugs are currently
      under investigation. This review focuses on the use of atypical antipsychotics in
      the treatment of bipolar disorder. We also present an overview concerning
      potential pharmakokinetic interactions based on the cytochrome P450 enzyme system
      when antipsychotics are combined with other mood stabilizing compounds. In
      conclusion, atypical antipsychotics should come to play an increasingly important
      role in the acute and long-term management of bipolar disorder, but there is a
      clear need for further controlled trials in this indication.

PMID- 12007075
TI  - [The diagnosis of frontotemporal dementia].
AB  - Frontotemporal Lobar Degeneration (FTDL) is a neurodegenerative disorder which is
      predominantly characterized by changes in behaviour and loss of cognitive
      abilities. Three major clinical syndromes have been identified, Frontotemporal
      dementia (FTD), in which changes in social behaviour predominate, Semantic
      Dementia (SD) which is characterized by a loss of semantic knowledge, and Primary
      Progressive Aphasia (PPA), a disorder of phonological and syntactic aspects of
      language. All subtypes of FTLD have insiduous onset and stepwise progression. The
      present review lists the clinical symptoms and main findings of the three FTLD
      subtypes, and discusses the difficulties of their diagnosis and differential
      diagnosis. The diagnosis of FTLD is based on the clinical consensus criteria of
      the Lund and Manchester groups, neuroradiological and neuropsychological
      investigations.

PMID- 12007076
TI  - [Emil Kraepelin's work at the Silesian Provincial Psychiatric State Hospital in
      Leubus].
AB  - Emil Kraepelin (1856-1926) worked as surgical resident physician at Leubus
      (Lubiaz) Psychiatric State Hospital (asylum) in Silesia from August 1884 to April
      1885. The asylum had been founded in a converted monastery as recommended by
      Johann Gottfried Langermann (1768-1832). Its first superintendent was Moritz
      Gustav Martini (1794-1875). Although no primary documents concerning Kraepelin's
      stay at Leubus could be found in the archives, the secondary sources and
      Kraepelin's own publications offer a good perspective on his Leubus period. Thus,
      his ground-breaking psychopathological study of confusion is based on patients
      observed at Leubus. Furthermore, it was here that his work on the major paper on
      falsifications of memory was begun. Kraepelin also finished the second part of
      his study "On the psychology of the comic" and wrote a postscript to his paper on
      the validity of Weber's law regarding light sensations. Since the then
      superintendent Wilhelm Alter (1843-1918) did not object to his residents doing
      scientific work, Kraepelin encouraged the voluntary resident physician Max
      Salomon (1860-?) to write a thesis on double-thinking. He also devoted a great
      deal of his time to writing reviews and to research in experimental psychology.
      Kraepelin's time at Leubus, similar to his Dresden period, are but a transitional
      phase for his final return to the university which he had left temporarily
      because he was disappointed and frustrated by the lack of career opportunities
      that suited his needs.

PMID- 12007077
TI  - [Seed and harvest - German psychiatry and psychology in Peru].
AB  - The influence of German psychiatry and German psychology in Peru was very strong
      in the beginning of the 20(th) Century. This is not well-known either in Germany
      or even in Peru or seems to be forgotten. The basis of it was the influence of
      German philosophy of the 19(th) and 20(th) centuries. A review is being given of
      the work of those that we consider to have been the pioneers of the German
      thought in these disciplines in Peru: Juan (Giovanni) Copello, Hermilio Valdizan
      (1885 - 1929), Dora Mayer (1868 - 1959), Enrique Encinas (1895 - 1971), Pedro
      Zulen (1889 - 1925), Honorio Delgado (1892 - 1967), Walter Blumenfeld (1882 -
      1967), and some of their pupils. Without these it would not have been possible to
      advance in the knowledge, neither would it had been possible to set the basis for
      a national psychology and psychiatry. Due to the development of the American
      theories that cropped up in the fifties and invaded the theoretical field as much
      as the practical one in both, psychology and psychiatry, this era has come to an
      end. These latter theories now prevail in the current university teaching. The
      "indigenous" sources, which helped to develop the psychological thought in the
      country were left aside, but are still very vivid in the discussions of
      international ethnopsychology and ethnopsychiatry.

PMID- 12007078
TI  - [Depression and cardiovascular disease: pathogenetic factors of the stress
      concept].
AB  - To date cardiovascular disorders still represent the most frequent cause of death
      in our western hemisphere. A number of prospective studies have now been able to
      show that patients with no prior history of heart disease run a higher risk of
      developing cardiovascular problems, if they either suffered a number of
      depressive symptoms or showed a depressive syndrome. Similarly, in patients who
      have suffered a myocardial infarction the presence of a depressive syndrome is
      frequently associated with poor clinical prognosis and outcome. Within this
      context the knowledge of the pathophysiological relationship between affective
      and cardiovascular disorders constitutes an essential element for instituting
      effective preventive measures for protecting depressed patients against the risk
      of suffering cardiovascular problems. The activation of stress-responsive systems
      during depressive episodes may contribute to metabolic risk factors and
      dysbalance of the autonomic heart regulation. The present overview provides a
      summary of current knowledge and findings within this area of research.

PMID- 12007079
TI  - Angiotensin type-1 receptor blockers in heart failure.
AB  - Chronic heart failure is a common condition with a poor prognosis, usually
      associated with poor exercise tolerance and debilitating symptoms despite optimal
      modern therapy. Standard therapy includes diuretics, digoxin, angiotensin
      converting enzyme inhibitors (ACEIs) and beta-blockers. Despite this, many
      patients remain symptomatic, and interest is high as to whether the angiotensin
      receptor blockers (ARBs) would offer further advantage to a patient already
      receiving quadruple therapy. In addition, some patients are intolerant of ACEIs,
      and for this group the ARBs seem a logical choice. This article reviews the
      evidence for the use of ARBs as a class in heart failure concentrating on
      clinical recommendations and clinical needs and evidence rather than purely on
      statistical issues of significance in trials. The trials to date have
      demonstrated clearly similar hemodynamic effects to those seen with ACEIs and
      variety of ancillary benefits such as improvements in endothelial function, anti
      thrombotic effects, and effects on neurohormonal inhibition. There is consistent
      evidence of a preservation of exercise tolerance when patients with heart failure
      are crossed over from stable ACEI therapy, and when added to ACEIs exercise
      tolerance appears to increase with ARBs. In terms of major outcomes, the two
      largest trials, Elite-II and Val-Heft, demonstrate that angiotensin receptor
      blockers probably have a clinical role in improving mortality and morbidity as an
      alternative to ACEIs in those patients unable to tolerate these agents, which
      remain, however, the first choice in unselected patients with heart failure.
      There is a worrying suggestion of a negative interaction when ARBs are added to
      beta-blockers, which is a reason for caution in using the ARBs, not a reason not
      to use beta-blockers.

PMID- 12007080
TI  - What is the place of beta-blockade in patients who have experienced a myocardial
      infarction with preserved left ventricular function? Evidence and
      (mis)interpretation.
AB  - Beta blockers have long been used in patients who have experienced a myocardial
      infarction. However, many new therapies are available for this patient group, and
      as a result, the current role of beta blockers may have become uncertain. In this
      article we address a series of questions related to the important and continuing
      role of beta blockade after myocardial infarction.

PMID- 12007081
TI  - Digoxin.
AB  - After 200 years of use, digitalis still appears to have a place in our
      armamentarium for heart failure and atrial fibrillation despite the proven
      survival benefits with ACE inhibitors and beta-blockers. Digoxin therapy is
      inexpensive and well tolerated and may result in considerable savings. Digoxin is
      the only oral inotrope that does not increase mortality in heart failure
      patients, particularly if low doses are being used. Digoxin therapy should be
      used in patients with systolic heart failure who continue to have signs and
      symptoms despite therapeutic doses of ACE inhibitors or diuretics or in patients
      with atrial fibrillation with or without heart failure for rate control.

PMID- 12007082
TI  - The importance of effect mechanism in the design and interpretation of clinical
      trials: the role of magnesium in acute myocardial infarction.
AB  - The design and interpretation of randomized clinical trials and of meta-analyses
      of trials should be informed by a biologically plausible hypothesis of treatment
      effect. Without some insight on likely mechanism, trial conditions may not be
      optimum to allow a true treatment effect to be detected. Judgments on mechanism
      underpin decisions on the appropriateness of pooling studies in meta-analysis.
      Where statistical heterogeneity of trial results is found, the possibility of
      true biological effect modification can only be assessed by considering potential
      treatment mechanisms. These can then be tested in carefully designed laboratory
      models. Meta-analysis of 12 randomized controlled trials of intravenous Mg(2+) in
      acute myocardial infarction gives a null effect (odds ratio 1.02, 95% CI 0.96 to
      1.08) with a fixed effects model, but with strong evidence of heterogeneity (P
      <.0001) due to a single large study in which Mg(2+) was generally given late and
      after fibrinolytic treatment. A random effects model gives a pooled odds ratio
      0.61 (95% CI 0.43 to 0.87, P = 0.006). Laboratory models show that timing of
      Mg(2+) administration before or after reperfusion critically determines whether
      myocardial protection occurs.

PMID- 12007083
TI  - Is aspirin "the weakest link" in cardiovascular prophylaxis? The surprising lack
      of evidence supporting the use of aspirin for cardiovascular disease.
AB  - It is currently fashionable to prescribe aspirin, long-term to people with or at
      high risk of vascular events due to atherosclerosis. There is a moderately
      conclusive evidence for a short-term benefit after an acute vascular event.
      However, there is remarkably little evidence that long-term aspirin is effective
      for the prevention of vascular events and managing side effects may be expensive.
      Reductions in nonfatal vascular events may reflect an ability of aspirin to alter
      cosmetically the presentation of disease without exerting real benefit.
      Cardiovascular medicine appears prone to fads and fashions that are poorly
      substantiated by evidence. The current fashion for prescribing aspirin is
      reminiscent of the now discredited practice of widespread prescription of class I
      anti-arrhythmic drugs for ventricular ectopics. We should learn from experience.

PMID- 12007084
TI  - BNP and congestive heart failure.
AB  - Brain natriuretic peptide (BNP), a peptide hormone secreted chiefly by
      ventricular myocytes, plays a key role in volume homeostasis. The plasma
      concentration of BNP is raised in various pathological states, especially heart
      failure. Many studies suggest that measurement of plasma BNP has clinical utility
      for excluding a diagnosis of heart failure in patients with dyspnea or fluid
      retention and for providing prognostic information in those with heart failure or
      other cardiac disease. It may also be of value in identifying patients after
      myocardial infarction in whom further assessment of cardiac function is likely to
      be worthwhile. Preliminary evidence suggests that measuring the plasma
      concentration of BNP may be useful in fine tuning therapy for heart failure.
      Artificially raising the circulating levels of BNP shows considerable promise as
      a treatment for heart failure. With simpler assay methods now available, it is
      likely that many physicians will measure plasma BNP to aid them in the diagnosis,
      risk stratification, and monitoring of their patients with heart failure or other
      cardiac dysfunction.

PMID- 12007091
TI  - Synthesis, structure and magnetism of homologous series of polycrystalline cobalt
      alkane mono- and dicarboxylate soaps.
AB  - Carboxylate-bridged chain complexes of Co(II) (the diaquacobalt(II) mono- and ,
      dialkanoates) form two homologous series of layered compounds which have been
      fully characterised both structurally and magnetically. The crystal structures of
      two selected members, [Co[CH3(CH2)10COO]2(H2O)2] and [Co[CH3(CH2)18COO]2(H2O)2],
      have been solved by X-ray powder diffraction and selected-area electron
      diffraction methods, and refined by the Rietveld technique. Crystal data:
      monoclinic, P 2(1)/a; a=9.688(1), b=7.5495(9), c=37.281(5) A, =96.70(3) primary,
      Z=4; and monoclinic, P 2(1)/a; a=9.7260(7), b=7.5477(7), c=57.53(1) A, =94.66(4)
      primary, Z=4, respectively. Their isomorphous structures contain layers of
      octahedral diaquacobalt(II) ions bonded to two chemically inequivalent
      alkanoates, one chelating and one bridging two Co atoms about 6.3 A apart, thus
      confirming the rare anti-anti conformation mode of the -RCOO groups recently
      proposed for diaquacobalt(II) ,-dodecanedioate. Extensive magnetic
      characterisation allowed estimation of the feeble antiferromagnetic coupling,
      which is weaker in the mono- than in the dialkanoate series.

PMID- 12007092
TI  - Topological analysis and charge density studies of an alpha-diimine macrocyclic
      complex of cobalt(II)--a combined experimental and theoretical study.
AB  - A combined experimental and theoretical study of the paramagnetic
      [Co(II)(C12H20N8)(H2O)2] x 2 ClO4 complex was made on the basis of the electron
      density distribution and topological analysis. Accurate single-crystal
      diffraction data were measured on a suitable crystal with Mo(K alpha) radiation
      at 125 K. The CoII ion is coordinated in a square bipyramidal fashion with four
      imino nitrogen atoms at the equatorial plane and two water molecules at the axial
      positions. The hydrogen-bonding interaction at 125 K between the coordinated
      water molecule and the ClO(4)(-) ion makes the space group different from that at
      298 K. Parallel MO calculations were made at UHF and DFT/UB3LYP. The agreement
      between experiment and theory is reasonably good. The chemical bonding
      characterization is presented in terms of the topological properties associated
      with bond critical points and the natural bond orbital (NBO) analysis as well.
      The Co-N(imino) and Co-O(water) bonds are dative bonds, where the lone-pair
      electrons of N or O serve as a -donor; however, a certain covalent character is
      identified in the Co-N(imino) bond. A delocalized C-N, N-N pi-bond model is
      proposed. The d-orbital energies of Co in this complex are such that E(d(xz)) is
      approximately equal to E(d(yz)) is approximately equal to E(dx(2-y2)) < E(d(z2))
      < E(d(xy)); notice that d(xy) and d(z2) are d(sigma) orbitals in this case. The
      Co(II) ion is in a low-spin d7 state with the singly occupied d(z2) orbital. The
      asphericity in electron density at Co and Cl nuclei is nicely demonstrated by the
      Laplacian of electron density. The envelope plot of the isovalue Laplacian
      surface around the nucleus gives the exact shape of such asphericity. The
      isovalue Laplacian surfaces of these two nuclei show significantly different VSCC
      character in both experimental and theoretical results.

PMID- 12007093
TI  - Planar-chiral (2E,7Z)- and (2Z,7E)-cyclonona-2,7-dien-1-yl carbamates by
      asymmetric, bis-allyic, alpha, alpha'-cycloalkylation--studies on their
      conformational stability.
AB  - Enantiomerically enriched (>80 % ee) (M,1R,2Z,7E)- and (M,1R,2E,7Z)-cyclonona-2,7
      dienyl carbamates have been synthesized by an intramolecular cycloalkylation of
      the corresponding 1-lithio-9-chloronona-2,7-dienyl carbamates. The
      enantioenriched precursors were generated by asymmetric deprotonation of the
      dienyl carbamates by means of n-BuLi/(-)-sparteine. The primarily obtained
      cyclononadienes, each bearing one element of planar and centre chirality, were
      formed by an , coupling of both allylic moieties. These are the thermodynamically
      less favoured epimers, which arise from those allyllithiums bearing the
      carbamoyloxy residue in a 1-endo position. Both (M,R)-cyclononadienes epimerize
      slowly (t(1/2) = 209 min and 328 min at 308 K) with inversion of the planar
      chirality to the corresponding, more stable (P)-epimers (ratios 3:97 and 30:70).
      The kinetics were measured by 1H NMR spectroscopy, the activation energies EA
      were found to be 26.4 and 27.5 kcal mol(-1). From quantum-chemical calculations
      with the B3LYP density functional, the epimerization process was shown to consist
      of two coupled major conformational changes with high energy barriers. The
      calculated values match well with the observed ones.

PMID- 12007094
TI  - Regioselective photolabeling of glycoprotein A in membranes.
AB  - We have developed a chemical method for directly identifying the amino acid
      residues of the transmembrane domain of a protein that are located right in the
      center of the membrane. Glycophorin A (GPA), the major sialoglycoprotein of human
      erythrocytes, was the first membrane protein whose primary sequence was
      elucidated, but its three-dimensional structure is still not known. GPA has been
      reconstituted into liposomes formed from dimyristoylphosphatidylcholine,
      dimyristoylphosphatidylserine, cholesterol, and a bola-amphiphilic phospholipidic
      photoactivatable probe (radioactive probe 1) by a detergent-mediated method.
      Electron microscopy confirmed the formation of spherical vesicular structures,
      and sucrose-density gradients revealed that the proteoliposomes comprised only
      one membrane fraction. Proteinase-K digestion of GPA in the proteoliposomes
      suggested that the orientation of GPA in reconstituted proteoliposomes was
      virtually identical to that observed in natural erythrocyte membranes. After
      photo-irradiation of the reconstituted proteoliposomes and in situ tryptic
      digestion, the photolabeled amino acid residues were analyzed by Edman
      degradation and their radioactivity was measured. Val80 and Met81, which had been
      assumed to be located near the center of the transmembrane domain of GPA, were
      indeed highly selectively photolabeled by probe 1. The new method might be
      applied to analyze the three-dimensional arrangement of the transmembrane domain
      of protein complexes that are made up from several subunits.

PMID- 12007095
TI  - Asymmetric chelated Claisen rearrangements in the presence of chiral ligands-
      scope and limitations.
AB  - Claisen rearrangements of glycine crotyl ester enolates in the presence of
      chelating metal salts and chiral ligands provide ,-unsaturated amino acids in a
      highly stereoselective fashion. Best results are obtained with electron
      withdrawing protecting groups, isopropylates of aluminum and magnesium, and the
      cinchona alkaloids as chiral ligands. While the use of quinine gives rise to the
      (2R)-configured amino acids, quinidine provides the opposite enantiomer. The
      different enantiomers can also be obtained by using only one of the chiral
      ligands by simply changing the reaction conditions. A mechanistic rational for
      the stereochemical outcome of the reaction is given, which is supported by
      several experiments.

PMID- 12007096
TI  - Total synthesis of the turrianes and evaluation of the DNA-cleaving properties.
AB  - The first total synthesis of three naturally occurring cyclophane derivatives
      belonging to the turriane family of natural products is described. Their
      sterically hindered biaryl entity is formed by reaction of the Grignard reagent
      derived from aryl bromide 10 with the oxazoline derivative 18, and the
      macrocyclic tether of the targets is efficiently forged by ring closing
      metathesis. While conventional RCM catalyzed by the ruthenium-carbene complexes
      33 or 34 invariably leads to the formation of mixtures of both stereoisomers with
      the undesirable (E)-alkene prevailing, ring closing alkyne metathesis (RCAM)
      followed by Lindlar reduction of the resulting cycloalkynes 37 and 38 opens a
      convenient and stereoselective entry into this class of compounds. RCAM can
      either be accomplished by using the tungsten alkylidyne complex [(tBuO)3 [triple
      bond] WCCMe3] or by means of a catalyst formed in situ from [Mo(CO)6] and para
      trifluoromethylphenol. The latter method is significantly accelerated when
      carried out under microwave heating. Furthermore, the judicious choice of the
      protecting groups for the phenolic -OH functions turned out to be crucial. PMB
      ethers were found to be compatible with the diverse reaction conditions en route
      to 3-5; their cleavage, however, had to be carried out under carefully optimized
      conditions to minimize competing O-C PMB migration. Turrianes 3-5 are shown to be
      potent DNA cleaving agents under oxidative conditions when administered in the
      presence of copper ions.

PMID- 12007097
TI  - A novel general route for the synthesis of C-glycosyl tyrosine analogues.
AB  - A general method for the synthesis of C-glycosyl amino acids is described here.
      The stereoisomerically pure tyrosine analogues alpha-L-4 and beta-L-6 are
      prepared in reasonable overall yields from allyl derivatives 10 and 11. The key
      step is a benzannulation procedure which is employed in the creation of the
      aromatic ring that bears the amino acid function.

PMID- 12007098
TI  - Synthesis of nucleopeptides by employing an enzyme-labile urethane protecting
      group.
AB  - Nucleoproteins are naturally occurring biopolymers in which the hydroxy group of
      a serine, a threonine, or a tyrosine moiety is linked through a phosphodiester
      group to the 3'- or 5'-end of a nucleic acid. For the study of the biological
      phenomena in which nucleoproteins are involved, for example, viral replication,
      nucleopeptides embodying the characteristic linkage between the peptide chain and
      the oligonucleotide may serve as powerful tools. However, as a result of the
      multifunctionality and the pronounced acid and base lability of nucleopeptides,
      their synthesis requires the application of a variety of orthogonally stable
      blocking groups, which can be removed under the mildest conditions. We have
      developed a new mild enzymatic deprotection method, that is, the penicillin G
      acylase-catalyzed hydrolysis of the N-phenylacetoxybenzyloxycarbony (PhAcOZ)
      group, for the synthesis of nucleopeptides. We demonstrate the wide applicability
      of this method by coupling the N-terminally deprotected nucleopeptides 31 a-c
      with PhAcOZ-protected amino acids and subsequent removal of the N-PhAcOZ group
      from fully protected nucleotetrapeptides 32 a,b with penicillin G acylase. The
      reaction conditions are very mild (pH 6.8) so that no undesired side reaction
      such as cleavage of the nucleotide bond or beta-elimination of the nucleotide was
      observed.

PMID- 12007099
TI  - On the intermediates in chiral bis(oxazoline)copper(II)-catalyzed
      enantioselective reactions--experimental and theoretical investigations.
AB  - The intermediates in the chiral bis(oxazoline)copper(II)-catalyzed reactions have
      been investigated by means of experimental and theoretical investigations. It is
      shown that the absolute configuration of the hetero-Diels-Alder adduct obtained
      from the reaction of ethyl glyoxylate with 1,3-cyclohexadiene in the presence of
      the chiral bis(phenyloxazoline)copper(II) is dependent on the solvent. In this
      case, a linear relationship between the enantiomeric excess (ee) and the
      dielectric constant of the solvent was observed. However, the enantiomeric excess
      for the adduct obtained with the chiral bis(tert-butyloxazoline)copper(II)
      complex is independent of the solvent. The addition of different coordinating
      solvents to the chiral catalysts was investigated and no effect on the
      enantioselectivity of the reaction was observed. A series of chiral bis(tert
      butyloxazoline)-, bis(phenyloxazoline)-, and bis(indaneoxazoline)copper(II)
      complexes has been prepared and characterized by X-ray analysis, and the
      similarity between the structures is discussed. For comparison, two related
      chiral bis(tert-butyloxazoline)- and bis(phenyloxazoline)zinc(II) complexes were
      also prepared and characterized. A series of chiral bis(oxazoline)copper(II)
      substrate (the substrate being glyoxal or methyl glyoxylate) complexes was
      investigated by means of ab initio calculations. Calculation of the total energy
      of the optimized structure of 17-, 19-, and 21-electron bis(oxazoline)copper(II)
      substrate complexes give the 17-electron complex as the most stable and the most
      reactive complex, while the 21-electron complex is less stable and also much less
      reactive. The optimized structures of both the 17-electron bis(tert
      butyloxazoline)- and bis(phenyloxazoline)copper(II)-substrate complexes show that
      the plane of the substrate molecule is twisted by approximately 40-45 degrees out
      of the bis(oxazoline)copper(II) plane, in agreement with the X-ray structures. On
      the basis of the experimental results, X-ray structures, and ab initio
      calculations, the structure of the intermediate(s) and reactivity of the chiral
      bis(oxazoline)copper(II)-substrate complexes are discussed.

PMID- 12007100
TI  - Chirotopical properties of cisoid enones from circular dichroism (CD) and
      anisotropic circular dichroism (ACD) spectroscopy.
AB  - Substituted cisoid 4-en-6-one steroids with isotropically distributed and
      partially oriented molecules were analyzed by circular dichroism (CD) and
      anisotropic circular dichroism (ACD) spectroscopy, respectively. CD and ACD data
      supplement their respective phenomenological information. For a series of C3
      substituted enones 1 to 7, the difference of CD (Delta epsilon) and ACD (Delta
      epsilon(A)) values, that is, Delta epsilon -Delta epsilon(A), vary in the n-*
      transition region in the same direction, independently of the nature and position
      (3 alpha or 3 beta) of the substituent. For 7-bromo-substituted enones 5 and 6
      the sign of the n-pi* CD band is opposite to that predicted by the enone helicity
      rule. The ACD data indicate that this behavior is a consequence of the effect of
      vibronic coupling caused by the 7-bromo substituent. In contrast to the results
      obtained for the series of C7-unsubstituted compounds 1 to 4, the intensity of
      the CD bands for 5 and 6 is determined by the vibrational progressions of a
      different symmetry. Therefore, the helicity rule must fail in both cases because
      the rule can only be applied to those vibrational transitions for which the rule
      was developed. The sign of the coordinates Delta epsilon(*)(II), estimated from
      the ACD data, yields additional stereochemical information that cannot be
      obtained from the CD data alone. The CD and ACD spectra in the region of the pi
      pi* transition vary for enones 1 to 4 in a different fashion and indicate
      dependence upon spatial orientation (3 alpha or 3 beta) of substituents. This
      dependence may lead to the possibility of extracting additional stereochemical
      information from the ACD spectra. Furthermore, the experimental findings indicate
      that the second CD band located at about 220 nm belongs to a forbidden transition
      and not to an allowed pi-pi* transition.

PMID- 12007101
TI  - The relevance of carbohydrate hydrogen-bonding cooperativity effects: a
      cooperative 1,2-trans-diaxial diol and amido alcohol hydrogen-bonding array as an
      efficient carbohydrate-phosphate binding motif in nonpolar media.
AB  - Carbohydrates with suitably positioned intramolecularly hydrogen-bonded hydroxyl
      and amide groups have the potential to act as efficient bidentate phosphate
      binders by taking advantage of sigma- and/or ,sigma,pi-H-bonding cooperativity in
      nonpolar solvents. Donor-donor 1,2-trans-diaxial amido alcohol (1) and diol (3),
      in which one of the donor centres is cooperative, are very efficient carbohydrate
      phosphate binding motifs. We have proven and quantified the key role of hydrogen
      bonding centres indirectly involved in complexation, which serve to generate an
      intramolecular H-bond (six-membered cis H-bond) in 1 and 3. This motif enhances
      the donor nature of the H-bonding centres that are directly involved in
      complexation. A comparison of the thermodynamic parameters of the complexes
      formed between phosphate and a cooperative (1-Phos) or anti-cooperative (2-Phos)
      bidentate H-bonded motif of a carbohydrate has allowed us to quantify the
      energetic advantage of H-bonding cooperativity in CDCl3 and CDCl3/CCl4 (1:1.3)
      (Delta Delta G degrees=-2.2 and -2.0 kcal mol(-1), respectively). The solvent
      dependences of the entropy and enthalpy contributions to binding provide a
      valuable example of the delicate balance between entropy and enthalpy that can
      arise for a single process, providing effective cooperative binding in terms of
      Delta G degrees.

PMID- 12007102
TI  - Bimetallic complexes from amphoteric group 13/15 ligands: syntheses and X-ray
      crystal structures.
AB  - Bimetallic, pentel-bridged complexes of the type [(dmap)Me2M-E(SiMe3)2-M'(CO)n]
      (M=Al, Ga; E=P, As, Sb; M'=Cr, Fe, Ni; DMAP=4-(dimethylamino)pyridine) are formed
      by reactions of DMAP-coordinated monomeric Group 13/15 compounds [(dmap)Me2M
      E(SiMe3)2] with the transition metal complexes [(Me3N)Cr(CO)5], [Fe3(CO)12], and
      [Ni(CO)4]. For the first time, this reaction offers a general pathway to
      compounds containing a Group 13 metal and a transition metal bridged by a pentel
      atom. Complexes prepared in this way were characterized by IR and multinuclear
      NMR spectroscopy and by single-crystal X-ray structure analysis. Their electronic
      and structural properties are discussed in detail. The Group 13/15 ligands are
      very weak acceptors, which is likely to be due to the electropositive Group 13
      metal, and the complexes feature comparatively long pentel-transition metal
      bonds. In addition, the synthesis and structural characterization of the parent
      DMAP-coordinated gallanes [(dmap)Me2Ga-E(SiMe3)2] (E=P, As) are reported.

PMID- 12007103
TI  - Bile salt aggregates in the gas phase: an electrospray ionization mass
      spectrometric study.
AB  - Helical and ordered structures have previously been identified by X-ray
      diffraction analysis in crystals and fibers of bile salts, and proposed as models
      of the micellar aggregates formed by trimeric or dimeric units of dihydroxy and
      trihydroxy salts, respectively. These models were supported by the results of
      studies of micellar bile salt solutions performed with different experimental
      techniques. The study has now been extended to the gas phase by utilizing
      electrospray ionization mass spectrometry (ESIMS) to investigate the formation
      and the composition of aggregates stabilized by noncovalent interactions,
      including polar (ion-ion, ion-dipole, dipole-dipole, hydrogen bonding etc.) and
      apolar (van der Waals and repulsive) interactions. The positive and negative
      ESIMS spectra of sodium glycodeoxycholate (NaGDC), taurodeoxycholate (NaTDC),
      glycocholate (NaGC), and taurocholate (NaTC) aqueous solutions, recorded under
      different experimental conditions, show in the first place that aggregates
      analogous to those present in micellar solutions do also exist in the gas phase.
      Furthermore, consistently with the condensed-phase model, the positive-ion
      spectra show that the trimers are the most stable oligomers among the aggregates
      of dihydroxy salts (NaGDC and NaTDC) whilst the dimers are the most stable among
      the aggregates of trihydroxy salts (NaGC and NaTC). Moreover, the binding energy
      of the constituent glycocholate salt units in most gaseous oligomers exceeds that
      of the corresponding taurocholate units. The ESIMS evidence has been confirmed by
      vapor-pressure measurements performed on NaGC and NaTC crystals and NaGDC and
      NaTDC fibers, the results of which show that the evaporation enthalpy of
      glycocholate exceeds that of taurocholate by some 50 kJ mol(-1).

PMID- 12007104
TI  - Synergism of catalysis and reaction center rehybridization in nucleophilic
      additions to cumulenes: the one-, two-, three-water hydrolyses of carbodiimide
      and methyleneimine.
AB  - The results of a theoretical study of the one-, two- and three-water hydrolyses
      of carbodiimide and the one- and two-water hydrolyses of methyleneimine are
      presented. All structures were optimized and characterized at the MP2(full)/6
      31G* level of theory. Energies for the one-water hydrolysis of carbodiimide were
      determined at numerous higher levels of theory, up to the QCISD(T)(fc)/6
      311+G(3df,2p)//MP2(full)/6-31G* level. The Delta E0(Delta G298) activation
      barriers for the rate-determining steps of the one-, two- and three-water
      hydrolyses of carbodiimide, respectively, are 44.8 (46.3), 29.3 (32.3) and 22.9
      (26.2) kcal mol(-1) at the MP2(full)/6-31G* level. The consideration of a second
      water molecule catalyzes the hydrolysis by 15.5 kcal mol(-1) on the E0 surface
      and by 14.0 kcal mol(-1) on the G298 surface with respect to the one-water
      hydrolysis. Placement of a third water molecule opposite the site of proton
      transfer catalyzes the reaction by an additional 6.4 kcal mol(-1) on the E0
      surface and by 6.1 kcal mol(-1) on the G298 surface. The catalytic effect of the
      third water molecule results from the synergistic effects of rehybridization and
      charge relaxation in the transition state. The charge relaxation in the
      transition state is illustrated through natural population analysis calculations
      on the pre-coordination complexes and the transition state structures. We also
      consider the placement of the third water molecule in the proton transfer chain
      and we show this to be of little catalytic relevance. The activation barriers
      determined for the one- and two-water hydrolyses of methyleneimine are Delta
      G298=51.9 and Delta G298=35.5 kcal mol(-1), respectively, and they are larger
      than for carbodiimide. The results are compared with the hydrolyses of carbon
      dioxide and formaldehyde.

PMID- 12007105
TI  - A theoretical analysis of the free-energy profile of the different pathways in
      the alkaline hydrolysis of methyl formate in aqueous solution.
AB  - The free-energy profile for the different reaction pathways available to the
      hydroxide ion and methyl formate in aqueous solution is reported for the first
      time. The theoretical analysis was carried out by using the cluster-continuum
      method recently proposed by us for calculating the free energy of solvation of
      ions. Unlike the gas-phase reaction, our results are consistent with the fact
      that the reaction occurs mainly by nucleophilic attack of the hydroxide on the
      carbonyl carbon to yield a tetrahedral intermediate (B(AC)2 mechanism). However,
      an additional pathway, in which the hydroxide ion acts as a general base and a
      water molecule coordinated to this ion acts as the nucleophile, is also predicted
      to be important. The relative importance of these pathways is calculated to be 87
      % and 13 %, respectively. The tetrahedral intermediate of the hydrolysis reaction
      has an estimated lifetime of 10 nanoseconds, and its conjugate acid has a pK(a)
      of 8.8. This tetrahedral intermediate is predicted to proceed to products by two
      pathways: elimination of methoxide ion (84 %) and by water catalyzed elimination
      of methanol (16 %). The less common reaction pathway, which involves attack of
      the hydroxide ion on the formyl hydrogen (decarbonylation mechanism) and leads to
      water, carbon monoxide, and methanol, is calculated to be only 3 kcal mol(-1)
      less favorable than the B(AC)2 mechanism. By comparison, direct attack of the
      hydroxide ion on the methyl group (B(AL)2 or S(N)2 mechanism) leading to an acyl
      oxygen bond cleavage has a very high free energy of activation and is not
      expected to be important. The theoretically observed activation free energy at
      298.15 K is calculated to be 15.5 kcal mol(-1), in excellent agreement with the
      experimentally measured value of 15.3 kcal mol(-1). This present model allows for
      a clear distinction between contributions due to solvation and those due to
      intrinsic (gas-phase) effects and proves to yield results in very good agreement
      with available experimental data.

PMID- 12007106
TI  - Synthesis and self-assembling properties of polymerizable organogelators.
AB  - In this paper we report the development of a family of polymerizable urea
      derivatives that are gelators for organic solvents. The design involves amino
      acid-based urea derivatives containing methacrylate functional groups. Several of
      the bis-ureas show excellent gelation properties in a variety of organic solvents
      at very low concentrations (1.5 mM). The self-assembling properties of these
      compounds were studied by X-ray powder diffraction, optical microscopy, and
      electronic microscopy. The molecules self-assemble into fibrous aggregates as
      indicated by scanning electron microscopy. Depending on the nature of the
      monomeric unit, the structure of the aggregates ranges from small to large fibers
      and planar sheets. In polar solvents, the molecules exhibit multilamellar packing
      modes. The organogels can be polymerized by photoirradiation leading to
      significant increases in stability as indicated by changes in phase-transition
      temperature. The morphology of the aggregates was seen to maintain a similar
      structure both before and after irradiation. This method provides a novel type of
      polymer with designed self-assembling architecture and also affords to a route to
      stabilized polymer gels.

PMID- 12007108
TI  - Establishment and Characterization of New Murine Breast Cancer Cell Lines.
AB  - The establishment of two new breast cancer cell lines, MXT(+) and MXT(-), derived
      from the murine breast cancer models MXT-M-3, 2 MC (hormone-sensitive) and MXT-M
      3, 2 (ovex) MC (hormone-insensitive), is described. Characterization of the cell
      lines was performed by investigation of morphology, steroid hormone receptor
      state, growth kinetics, and drug response as well as by cytogenetic analysis.
      MXT(+) contains estrogen receptors (ER; 6.9 fmol/mg protein) as well as
      progesterone receptors (PgR; 9.2 fmol/mg protein) and therefore is inhibited by
      tamoxifen (Tam). MXT(-) proved to be ER(-) but PgR(+) (23.4 fmol/mg protein) and,
      as expected, resistant against Tam.The sensitivity of MXT(+) and MXT(-) against a
      pattern of therapeutically established anti-breast cancer drugs (cDDP, cisplatin;
      JM-8, carboplatin; DX, adriamycin; 5-FU, 5-fluorouracil; MTX, methotrexate; VLB
      vinblastine) was studied by use of a computerized, kinetic chemosensitivity assay
      based on quantification of biomass by staining cells with crystal violet. For
      each compound the inhibition profile reflecting cytostatic, transient cytotoxic,
      or cytocidal drug effects as well as development of resistance was evaluated. The
      following order of activity was found: MTX >, VLB >/= DX > cDDP >/= 5-FU > JM-8.
      The test data of 5-FU, VLB, cDDP, and Tam on MXT(+) as well as on MXT(-) were
      compared with those from studies on ER(+) and ER(-) human breast cancer cell
      lines (MCF-7, ZR-75-1, T-47-D, and MDA-MB-231, respectively). They revealed
      comparable inhibition profiles and sensitivities of human and murine breast
      cancer cell lines, an indication that the results achieved in combined in vitro
      /in vivo tests by use of the murine test models MXT(+), MXT(-), MXT-M-3, 2 MC,
      and MXT-M-3, 2(ovex) MC are relevant for therapy in humans.

PMID- 12007109
TI  - Synthesis and Antihypertensive Activities of New 1, 4-Dihydropyridine Containing
      Nitroimidazolyl Substituent with a Nitrooxy Group at the 3-Ester Position.
AB  - New analogues of nifedipine, in which the ortho nitrophenyl group of position 4
      is replaced by 1-methyl-4-nitro-5-imidazolyl or 1-methyl-5-imidazolyl with a
      nitrooxy group at the 3-ester position were synthesized, and the antihypertensive
      activity of the compounds was examined by the tail-cuff method and compared with
      TNG and nifedipine. Compounds 11g, 11i-11m, 110, 11r, and 11v showed activity
      similar to nifedipine and TNG.

PMID- 12007110
TI  - Photochemical Study of Hexahydroquinoline Derivatives - A New Group of Calcium
      Antagonists.
AB  - The photochemical stability of 2, 6, 6-trimethyl-3-carbmethoxy-4-phenyl-5-oxo-1,
      4, 5, 6, 7, 8-hexahydroquinoline (HHQ) derivatives with different substituents on
      the phenyl ring (-Cl, -NO(2), -CF(3), -CH(3), -OCH(3)) has been studied.The
      process of photodegradation was studied by UV spectrophotometry. The rate of
      photodegradation was found to depend on the type and position of the substituent
      in the phenyl ring. The compounds most susceptible to the damaging effect of
      light proved to be those containing the nitro group, in particular with the
      substituent in the ortho position of the aromatic ring. Derivatives with alkyl (
      CH(3)) and halo-alkyl (-CF(3)) substituents showed the greatest photochemical
      stability. The compounds with substituents in the ortho position were found to be
      much less photostable than the meta isomers. The quantum yield values obtained
      ranged from 10(-4) to 10(-3), indicating the occurrence of secondary
      photochemical processes initiated by the primary products of decomposition.

PMID- 12007111
TI  - Synthesis and Biological Evaluation of 4-(4-(Alkyl-and
      Phenylaminocarbonyl)benzoyl)benzoic Acid Derivatives as Non-steroidal Inhibitors
      of Steroid 5alpha-Reductase Isozymes 1 and 2.
AB  - The synthesis and biological evaluation of 4-(4-(alkyl- and phenylaminocarbonyl)
      benzoyl)benzoic acids (4a-4d) as non-steroidal inhibitors of steroid 5alpha
      reductase are described. The compounds were tested in vitro for inhibitory
      activity toward rat and human 5alpha-reductase isozymes 1 and 2 at a
      concentration of 10 &mgr;M.The most active inhibitor for the human type 2 isozyme
      was 4-(4-(phenylaminocarbonyl)benzoyl) benzoic acid, compound 4c (IC (50) = 0.82
      &mgr;M).

PMID- 12007112
TI  - Hydrogels Formed by Crosslinked Poly(vinyl alcohol) as Sustained Drug Delivery
      Systems.
AB  - Poly(vinyl alcohol) was crosslinked with ethylene glycol diglycidyl ether to
      obtain hydrogel-forming polymers. The polymers were also substituted with oleoyl
      chloride, providing hydrogels with weak solubility.These new polymeric materials
      were evaluated for the formulation of sustained drug delivery systems. Vancomycin
      hydrochloride was used as a peptidic model drug whose sustained release should
      minimize its inactivation in the upper part of the gastrointestinal tract. Spray
      dried mixtures of the drug and the polymer [at 1:4 and 1:8 (w:w) ratios] were
      prepared and the release of the drugs from the mixtures was evaluated in vitro at
      pH 2.0, 5.5, 7.4, and 8.0. The results indicated that the crosslinked polymers
      slowed down the release of the drugs with respect to the pure drug at each pH.The
      degree of crosslinking of ethylene glycol diglycidyl ether and the extent of
      substitution with oleoyl chloride were found to influence drug release.

PMID- 12007113
TI  - Synthesis and Antimicrobial Activity of Hydroxyalkyl- and Hydroxyacyl-phenols and
      Their Benzyl Ethers.
AB  - New phenolic compounds with hydrophilic side chains were prepared from 4
      benzyloxybenzaldehyde and alkenyl magnesium bromides, followed by Sharpless
      dihydroxylation and hydrogenolytic removal of the benzyl group. The resulting
      compounds were tested in an agar diffusion assay against gram positive bacteria,
      gram negative bacteria, and against the fungi Candida glabrata and Aspergillus
      niger.

PMID- 12007114
TI  - Preparation and Antibacterial Activity of 3-Methyl-1-p-substituted Phenylpyrazole
      5-thiol.
AB  - 3-Methyl-1-phenylpyrazole-5-thiol (3a) and its p-nitro-(5) and p-fluorophenyl (8)
      derivatives were prepared as potential antimicrobial agents in relatively good
      yields. Compounds 3a and 8 showed good antibacterial activities against MRSA, S.
      aureus, S. epidermidis, E. faecalis, E. faecium, and S. pyogenes. Moreover,
      compound 3a also showed a synergistic effect with some aminoglycosides.

PMID- 12007115
TI  - Determination of Amlodipine in Pharmaceutical Formulations by Differential-Pulse
      Voltammetry with a Glassy Carbon Electrode.
AB  - A differential-pulse voltammetric method was developed for the determination of
      amlodipine based on the oxidation of the dihydropyridine group on the surface of
      glassy carbon electrode under stationary and rotating conditions. The experiments
      were conducted in a supporting electrolyte consisting of 0.2 MKCl, 0.1 Mphosphate
      buffer, and 10 % (v/v) methanol during investigation of initial potential and pH
      effects. No adsorption effect was observed on using an initial potential of 0
      mVand the supporting electrolyte solution at pH 5.5 under both stationary and
      rotating conditions. The factor affecting the voltammetric current was
      diffusional in the range of 200-1000 rpm for rotating, and 2-40 mV s(-1) for
      stationary conditions up to a concentration of 0.04 mg mL(-1) amlodipine. The
      limit of detection (LOD) and the limit of quantitative (LOQ) for the rotating and
      stationary techniques were found to be 0.004 and 0.0072 mg mL(-1) (for S/N = 3.3)
      and LOQ 0.012 and 0.022 mg mL(-1) (for S/N = 10), respectively. The proposed
      method was applied to the tablets containing amlodipine and according to the
      statistical evaluations acceptable results were obtained at the 95 % probability
      level.

PMID- 12007118
TI  - Chromatographic and electrophoretic migration parameters in capillary
      electrochromatography.
AB  - Chromatographic retention factor, k', as defined in high-performance liquid
      chromatography (HPLC) in terms of the migration times of the separand and the
      inert tracer, has limited applicability to capillary electrochromatography (CEC)
      when both chromatographic and electrophoretic processes determine the magnitude
      of the overall migration rates of the separands. This situation is unlike that in
      HPLC, where k' serves as a useful peak locator for the various sample components,
      as well as, provides thermodynamic insights into the interactions between the
      components and the stationary phase. Most publications have borrowed the
      definition of k' from HPLC and applied it on CEC. However, due to the dual
      separation mechanisms that are in action in CEC, the system is significantly
      complicated in comparison to that of HPLC. This paper discusses the impossibility
      of defining with a k' which would have all the attributes that it has in regular
      chromatography. The interplay of the two separation mechanisms in determining the
      overall migration process in CEC is discussed and the various definitions of the
      electrochromatographic retention factor are presented.

PMID- 12007119
TI  - Surfactant-mediated capillary electrochromatography with octadecyl-silica- packed
      capillary columns for the separation of nonpolar compounds. Case of pyrethroid
      insecticides.
AB  - Capillary electrochromatography (CEC) with octadecyl-silica-packed capillary
      columns was evaluated in the separation of nonpolar compounds, e.g., pyrethroid
      insecticides, using surfactant-rich mobile phases. This novel concept is referred
      to as surfactant-mediated capillary electrochromatography (SM-CEC), and is based
      on including a charged surfactant, namely sodium di-2-ethylhexyl sulfosuccinate
      (DOSS), in the mobile phase. Under these conditions, DOSS plays the role of a
      slowly moving pseudostationary phase so that solutes are partitioned between a
      mobile phase, a fixed stationary phase and a slowly moving pseudostationary
      phase. The SM-CEC system was investigated with pyrethroid insecticides over a
      wide range of DOSS and acetonitrile concentrations in the mobile phase.
      Pyrethroid insecticides, which are very hydrophobic solutes consisting of
      geometric isomers and diastereomers, were better resolved in SM-CEC than in
      straight CEC.

PMID- 12007120
TI  - Novel approach for fritless capillary electrochromatography.
AB  - At present, the main limitation for the further adoption of capillary
      electrochromatography (CEC) in the (routine) laboratory is caused by the lack of
      reproducible and stable columns. The main source of column instability is
      concentrated in the frits needed to retain the packed bed inside the CEC
      capillary. The sintering process used to prepare the frits can be rather
      problematic and irreproducible, particularly for small stationary phase particles
      and wide column diameters. Since the (surface) composition of the frits is
      different from the bulk stationary phase packing, different electroosmotic flow
      (EOF) velocities are generated. This effect is assumed to be primarily
      responsible for rapid column destruction. In this contribution, a novel approach
      for the preparation of fritless CEC capillaries is presented and evaluated. Using
      5 microm Hypersil ODS particles, separation efficiencies in the range of 130,000
      200,000 plates/m were obtained. In a 100 microm inner diameter packed column,
      electrical currents up to 50 microA could be tolerated without negative effects
      such as bubble formation. The prepared CEC columns were found to be stable and
      could easily be operated continuously for several days without column damage. An
      additional advantage of the proposed tapering approach is that application of
      pressure on the in- and outlet vial during separation was not required to prevent
      bubble formation.

PMID- 12007121
TI  - Nucleoside monophosphates recognition using macrocyclic polyamine bonded phase in
      capillary electrochromatography.
AB  - An open-tubular wall-coated macrocyclic polyamine capillary column (70 cm x 75
      microm ID) with 50 cm effective length for the separation of nucleoside
      monophosphates is described. Some parameters with respect to concentration, pH,
      composition of the buffer, and voltage in order to optimize the separation were
      studied. The coated capillary showed reversed electroosmotic flow (EOF), allowing
      anions to be separated in the co-EOF mode. Baseline separations were achieved for
      the eight nucleotides in less than 26 min using a background electrolyte
      consisting of H(3)PO(4)-NaH(2)PO(4) (30 mM, pH 3.10), an applied voltage of -15
      kV, and detection at 254 nm. The macrocyclic polyamine on the capillary wall
      introduced anion coordination for the interaction with the analytes, the strength
      of which could be moderated by the type and concentration of the competing ion
      used in the background electrolyte (BGE). With a low concentration of the
      competing ion (phosphate ion), the migration behavior followed that obtained in
      the electrophoretic system. Increasing the concentration of the competing ion
      resulted in a faster migration and more complete elution of the analyte. The
      method established was also employed for the analysis of nucleotides in
      mushrooms. Aqueous extracts of mushrooms from different species and various
      extraction methods were injected directly for the analysis. Uridine 5'
      monophosphate, guanosine 5'-monophosphate, adenosine 5'-monophosphate, and
      cytidine 5'-monophosphate, were found in the sample tested.

PMID- 12007122
TI  - Separation of peptides on mixed mode of reversed-phase and ion-exchange capillary
      electrochromatography with a monolithic column.
AB  - The mixed mode of reversed phase (RP) and strong cation-exchange (SCX) capillary
      electrochromatography (CEC) based on a monolithic capillary column has been
      developed. The capillary monolithic column was prepared by in situ
      copolymerization of 2-(sulfooxy)ethyl methacrylate (SEMA) and ethylene
      dimethacrylate (EDMA) in the presence of porogens. The sulfate group provided by
      the monomer SEMA on the monolithic bed is used for the generation of the
      electroosmotic flow (EOF) from the anode to the cathode, but at the same time
      serves as a SCX stationary phase. A mixed-mode (RP/SCX) mechanism for separation
      of peptides was observed in the monolithic column, comprising hydrophobic and
      electrostatic interaction as well as electrophoretic migration at a low pH value
      of mobile phase. A column efficiency of more than 280,000 plates/m for the
      unretained compound has been obtained on the prepared monoliths. The relative
      standard deviations observed for t(0) and retention factors of peptides were
      about 0.32% and less than 0.71% for ten consecutive runs, respectively. Effects
      of mobile phase compositions on the EOF of the monolithic column and on the
      separation of peptides were investigated. The selectivity on separation of
      peptides in the monolithic capillary column could be easily manipulated by
      varying the mobile phase composition.

PMID- 12007123
TI  - Separation of enantiomers by nanoliquid chromatography and capillary
      electrochromatography using a bonded cellulose trisphenylcarbamate stationary
      phase.
AB  - A cellulose trisphenylcarbamate-bonded chiral stationary phase was applied to
      nano-liquid chromatography (nano-LC) and capillary electrochromatography (CEC)
      with nonaqueous and aqueous solutions as the mobile phases. Several chiral
      compounds were successfully resolved on the prepared phase by nano-LC. The
      applicability of nonaqueous CEC on a cellulose derivative stationary phase was
      investigated with the organic solvents methanol, hexane, 2-propanol, and
      tetrahydrofuran (THF) containing acetic acid, as well as triethylamine as the
      mobile phases. Enantiomers of warfarin and praziquantel were baseline-resolved
      with plate numbers of 82,300 and 38,800 plates/m, respectively, for the first
      eluting enantiomer. The influence of applied voltage, concentration of nonpolar
      solvent, apparent pH, and buffer concentration in the mobile phase on the
      electroosmotic flow (EOF) and the mobility of the enantiomers was evaluated.
      Enantioseparations of trans-stilbene oxide and praziquantel were also achieved in
      aqueous CEC with plate numbers of 111,100 and 107,400 plates/m, respectively, for
      the first eluting enantiomer. A comparison between nonaqueous CEC and aqueous CEC
      based on a cellulose trisphenylcarbamate stationary phase was discussed. Pressure
      assisted CEC was examined for the chiral separation of praziquantel and faster
      analysis with high enantioselectivity was acquired with the proper pressurization
      of the inlet vial.

PMID- 12007124
TI  - Immunoaffinity screening with capillary electrochromatography.
AB  - Highly efficient capillary electrochromatographic separations of cardiac
      glycosides and other steroids are presented. Employing butyl-derivatized silica
      particles as stationary phase resulted in a nearly three times faster
      electroosmotic flow (EOF) compared to capillary electrochromatography (CEC) with
      octadecyl silica particles. On-column focusing with a preconcentration factor of
      180 was performed and separation efficiencies of up to 240,000 plates per meter
      were obtained. Using label-free standard UV absorbance, detection limits of 10-80
      nM were reached for all steroids tested. For screening of cardiac glycosides,
      e.g., digoxin and digitoxin in mixtures of steroids, CEC was combined with
      immunoaffinity extraction using immobilized polyclonal anti-digoxigenin
      antibodies and F(ab) fragments. Simply adding small amounts of antibody carrying
      particles to the samples and comparing chromatograms before and after antibody
      addition allowed screening for high affinity antigens in mixtures with moderate
      numbers of compounds. Under conditions of competing antigens, affinity
      fingerprints of immobilized anti-digoxigenin and anti-digitoxin antibodies were
      obtained, reflecting the cross-reactivity of eleven steroids. The method provides
      high selectivity due to the combination of bioaffinity interaction with highly
      efficient CEC separation and UV detection at several wavelengths in parallel.
      This selectivity was exploited for the detection of four cardiac glycosides in
      submicromolar concentrations in an untreated urine sample.

PMID- 12007125
TI  - Concurrent analysis of nucleoside reverse transcriptase inhibitors in a pool of
      endogenous nucleosides by short-end injection-capillary electrochromatography on
      a beta-cyclodextrin-bonded stationary phase.
AB  - As part of our on-going study of the analysis of anti-human immunodeficiency
      virus (HIV) nucleosides, a capillary electrochromatography (CEC) method has been
      developed for the concurrent analysis of nucleoside HIV reverse transcriptase
      inhibitors (NRTIs) in a pool of endogenous nucleosides. Up to now, beta
      cyclodextrin-bonded silica stationary phases have mainly been dedicated to the
      separation of enantiomers; however, these polysaccharides can be also be used in
      achiral way. This work aims at showing how CEC performed on a beta-cyclodextrin
      bonded silica stationary phase can be used to concurrently resolve zidovudine
      (AZT), lamivudine (3TC), didanosine (ddA) and its administrated form (ddI),
      stavudine (d4T) and hivid (ddC) in a mixture of adenosine (A), cytidine (C),
      guanosine (G), thymidine (T) and uridine (U). The influence of several parameters
      (pH buffer, ionic strength, acetonitrile content, temperature and voltage) on
      both the retention times and the retention factors has been investigated using
      the short-end injection technique to achieve baseline separation in a short-time
      analysis before quantitation. Moreover, the retention factors of the charged
      solutes in short-end injection-CEC were calculated using theoretically derived
      equations, allowing for the actual voltage drop in the packed section of the
      semipacked CEC capillary.

PMID- 12007126
TI  - Open-tubular capillary electrochromatography using capillary columns chemically
      bonded with the new host molecules calix[6]crown, calix[6]arene.
AB  - Two host molecules, p-tert-butylcalix[6]-1,4-crown-4 and p-tert
      butylcalix[6]arene were prepared and attached onto the inner surfaces of
      capillaries for open-tubular electrochromatography with the aid of gamma
      glycidoxypropyl-trimethoxysilane (KH-560) as bridging agent. The successful
      bonding was confirmed by infrared (IR) results and greatly decreased
      electroosmotic flow (EOF). Parameters affecting separation, such as buffer pH and
      organic modifier were studied. The two novel stationary phases were evaluated by
      the separation of isomeric toluidines, a mixture of pyridine and isomeric
      picolines, and isomeric dihydroxybenzenes; comparisons between capillaries coated
      with the two stationary phases and bare capillary were investigated. The special
      selectivity of these two novel stationary phases showed a certain extent of
      supramolecular interactions between stationary phases and solutes.

PMID- 12007127
TI  - Predicting and evaluating separation quality of micellar electrokinetic capillary
      chromatography by artificial neural networks.
AB  - Computer-aided optimization of micellar electrokinetic capillary chromatography
      (MEKC) separations was demonstrated by artificial neural networks (ANNs) using a
      Levenberg-Marquardt algorithm and an orthogonal experimental design. A novel
      criterion, named Q, for evaluating the separation quality of MEKC was firstly
      presented, which considered both separation selectivity and analysis time. MEKC
      separation conditions of seven plant hormones were then simulated and optimized
      using ANNs based on this novel criterion. The result was further compared to that
      obtained using ANNs based on a traditionally used criterion of overall
      normalization resolution (named r). Finally, the separation under optimum
      conditions predicted by ANNs using the criterion Q was compared to, and proved to
      be better than that obtained by empirical step-by-step optimization procedures.
      This method may also be adapted to other separation methods due to its
      generality.

PMID- 12007128
TI  - Effect of pendent group structures on the chemical selectivity and performance of
      sulfonated copolymers as novel pseudophases in electrokinetic chromatography.
AB  - Amphiphilic copolymers of 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS)
      with dihydrocholesteryl acrylate (pDHCHAt) or tert-octyl acrylamide (ptOAm) as
      comonomers were synthesized, characterized and used as new polymeric
      pseudostationary phases in electrokinetic chromatography. High-efficiency
      separations with theoretical plates around 500,000 to 870,000/m were achieved.
      Linear solvation energy relationships analysis of 20 solutes was performed to
      investigate the retention mechanism. Polycyclic aromatic hydrocarbons (PAHs) were
      separated under 30% v/v acetonitrile. The separation of nine aromatic model
      solutes by pDHCHAt showed significantly different selectivity from that of sodium
      dodecyl sulfate. Although only minor difference in selectivity was found for
      small aromatic compounds on pDHCHAt and poly(AMPS-lauryl acrylate), significantly
      different retention mechanism was found for PAHs and n-dodecanophenone comparing
      both copolymers. Significant chemical selectivity difference was found for
      selected small aromatic compounds on ptOAm and poly(AMPS-stearyl acrylamide).

PMID- 12007129
TI  - Spherical molecularly imprinted polymer particles: a promising tool for molecular
      recognition in capillary electrokinetic separations.
AB  - Spherical molecularly imprinted polymer particles obtained via precipitation
      polymerization, were introduced as a pseudostationary phase in capillary
      electrophoresis (CE) to study molecular recognition. Analyses were performed via
      a partial filling technique using (+)-ephedrine-imprinted microspheres (100-200
      nm) which were polymerized from methacrylic acid and 1,1,1
      Tris(hydroxymethyl)propanetrimethacrylate using acetonitrile as the solvent. The
      influence of pH and the modifier content on the separation was investigated. A
      0.1% w/v suspension in an aqueous 10 mM phosphate buffer (pH 2.5 with 40%
      acetonitrile) was hydrodynamically injected into the CE system (80% of the
      effective capillary length) and led to full baseline separation of racemic
      ephedrine within 10 min.

PMID- 12007130
TI  - Studies on the chiral recognition of peptide enantiomers by neutral and sulfated
      beta-cyclodextrin and heptakis-(2,3-di-O-acetyl)-beta-cyclodextrin using
      capillary electrophoresis and nuclear magnetic resonance.
AB  - The separation of dipeptide and tripeptide enantiomers using a neutral single
      isomer cyclodextrin (CD) derivative, heptakis-(2,3-di-O-acetyl)-beta-CD (DIAC
      beta-CD), was investigated with respect to the amino acid sequence applying
      standard separation conditions. With only one exception the DD-enantiomers
      migrated faster than the LL-stereoisomers. Separations obtained for the same set
      of peptides using beta-CD and the sulfated single isomer derivatives heptakis
      (2,3-di-O-acetyl-6-sulfo)-beta-CD (HDAS-beta-CD) and heptakis-6-sulfo-beta-CD (HS
      beta-CD) revealed identical enantiomer migration order in the presence of the 2,3
      disubstituted derivatives DIAC-beta-CD and HDAS-beta-CD. In contrast, reversed
      migration sequence was found for beta-CD and HS-beta-CD compared to DIAC-beta CD
      and HDAS-beta-CD indicating the importance of the substitution pattern on the
      wider rim of the CD cavity on the chiral recognition of the peptide enantiomers
      by the CDs. Nuclear magnetic resonance (NMR) experiments indicated different
      complexation modes between the enantiomers and the CDs depending on the presence
      of acetyl substituents on the wider rim of the CD torus. Thus, the CD-induced
      chemical shifts observed in samples containing Ala-Phe or Ala-Tyr and beta-CD or
      HS-beta-CD were consistent with an inclusion of the aromatic moiety into the CD
      cavity. Although the CD-induced chemical shifts in the presence of DIAC-beta-CD
      and HDAS-beta-CD did not allow direct conclusions on the complexation mode they
      substantially differed from those observed in the presence of 2,3-unsubstituted
      CDs indicating different structures of the peptide-CD complexes.

PMID- 12007131
TI  - Chiral recognition of functionalized cyclodextrins in capillary electrophoresis.
AB  - The chiral recognition of hydroxypropylated, dimethylated, and sulfated
      cyclodextrins was evaluated by utilizing them as chiral additives in capillary
      electrophoresis. Although each selector yielded enantiomeric separations of most
      of the target analytes, differences were observed in the electrophoretic results
      for the different derivatized cyclodextrins and for additives having varying
      degrees of substitution. The results for the sulfated cyclodextrins also
      highlighted the importance of knowing the degree of substitution as well as the
      location of the substituents when comparing chiral selectors.

PMID- 12007132
TI  - Chiral separation of anionic and neutral compounds using a hepta-substituted
      cationic beta-cyclodextrin as a chiral selector in capillary electrophoresis.
AB  - Enantiomeric separations of six anionic and two neutral racemates were achieved
      using a fully substituted heptakis(6-hydroxyethylamino-6-deoxy)-beta-cyclodextrin
      (beta-CD-EA) as a chiral selector. As beta-CD-EA provides a dynamic coating on
      the capillary wall, reverse-polarity capillary electrophoresis (CE) configuration
      is applied for separations of anionic and neutral chiral compounds. Chiral
      separations of various classes of anionic and neutral enantiomers were found to
      be highly dependent on pH because the degree of protonation of beta-CD-EA can
      alter the shape of the CD cavity by charge repulsion, altering complexation,
      aiding selectivity, and leading to better enantiomeric separation. In general,
      the chiral resolution of anionic enantiomers was enhanced at higher pH. This
      suggests that carboxylate or phosphate groups on the analyte may interact with
      the protonated amine groups of cationic CD. The successful enantioseparation was
      achieved in a pH range of 6.6-7.8 for all six anionic analytes, in the presence
      of 10 mM beta-CD-EA.

PMID- 12007133
TI  - Chiral separation of polychlorinated biphenyls using a combination of
      hydroxypropyl-gamma-cyclodextrin and a polymeric chiral surfactant.
AB  - Chiral separation of moderately to highly hydrophobic polychlorinated biphenyls
      (PCBs) using a conventional chiral micelle or a polymeric chiral surfactant, as
      the single chiral selector is very difficult since the hydrophobic interactions
      between the chiral PCB and the monomeric or polymeric surfactant is very strong.
      Combined use of a polymeric chiral surfactant, polysodium N-undecanoyl-D-valinate
      (poly-D-SUV) with hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) was successful
      in cyclodextrin modified electrokinetic chromatography (CD-EKC) enantioseparation
      of PCB congeners. Addition of HP-gamma-CD to the background electrolyte
      containing poly-D-SUV functioned to improved chiral resolution for the PCBs and
      reduce the analysis time for these congeners. In addition, concentration of
      methanol, concentration of 2-(N-cyclohexylamino) ethanesulfonic acid (CHES)
      buffer and separation voltage was also varied to optimize multicomponent
      separation of five chiral PCBs. Simultaneous separation and enantioseparation of
      all five PCBs was possible in less than 50 min under optimized conditions that
      requires a 5 mM CHES solution buffered at about pH 10 with 1.5% w/v (ca. 60 mM)
      poly-D-SUV and 16 mM HP-gamma-CD. In addition, 1 M urea and 20% v/v methanol
      should be added as organic modifier and the capillary temperature maintained at
      45 degrees C. As expected the polymeric surfactant showed improved chiral
      resolution of PCBs over conventional micelles of SUV. Under optimized conditions,
      when CD-EKC of chiral PCBs using poly-D-SUV was compared to sodium dodecyl
      sulfate (SDS), better resolution, higher efficiency and shorter analysis time was
      achieved with poly-D-SUV.

PMID- 12007134
TI  - The use of a highly sulfated cyclodextrin for the simultaneous chiral separation
      of amphetamine-type stimulants by capillary electrophoresis.
AB  - We investigated the simultaneous chiral separation of nine amphetamine type
      stimulants (dl-norephedrine, dl-norpseudoephedrine, dl-ephedrine, dl
      pseudoephedrine, dl-amphetamine, dl-methamphetamine, dl-methylenedioxyamphetamine
      (MDA), dl-methylenedioxymethamphetamine (MDMA), and dl
      methylenedioxyethylamphetamine (MDEA)) by capillary electrophoresis using highly
      sulfated gamma-cyclodextrin (SU(XIII)-gamma-CD) as a chiral selector. Three
      different approaches using SU(XIII)-gamma-CD with 50 mM phosphate background
      electrolyte were designed; (I) high CD concentration (10 mM SU(XIII)-gamma-CD) at
      neutral pH (pH 7.0) in the normal polarity mode, (II) low CD concentration (1.0
      mM) at low pH (pH 2.6) in the normal polarity mode and (III) high CD
      concentration at low pH (pH 2.6) in the reversed-polarity mode. In mode (II), the
      effects of adding three neutral CDs (beta-CD, dimethyl-beta-CD and hydroxypropyl
      beta-CD) were also investigated. The best separation was obtained after
      optimizing mode (III) as follows: run buffer of 10 mM SU(XIII)-gamma-CD with 50
      mM phosphate background electrolyte at pH 2.6, applied voltage of -12 kV and
      capillary temperature of 15 degrees C.

PMID- 12007135
TI  - Aptamers as analytical reagents.
AB  - Many important analytical methods are based on molecular recognition. Aptamers
      are oligonucleotides that exhibit molecular recognition; they are capable of
      specifically binding a target molecule, and have exhibited affinity for several
      classes of molecules. The use of aptamers as tools in analytical chemistry is on
      the rise due to the development of the "systematic evolution of ligands by
      exponential enrichment" (SELEX) procedure. This technique allows high-affinity
      aptamers to be isolated and amplified when starting from a large pool of
      oligonucleotide sequences. These molecules have been used in flow cytometry,
      biosensors, affinity probe electrophoresis, capillary electrochromatography, and
      affinity chromatography. In this paper, we will discuss applications of aptamers
      which have led to the development of aptamers as chromatographic stationary
      phases and applications of these stationary phases; and look towards future work
      which may benefit from the use of aptamers as stationary phases.

PMID- 12007136
TI  - Off-line and in-line determination of catechol- O-methyltransferase activity in a
      capillary electrophoretic system.
AB  - The use of capillary electrophoresis for the determination of catechol-O
      methyltransferase (COMT) activity with dihydroxybenzoic acid as a substrate was
      investigated. Both an off-line and in-line capillary electrophoresis
      determination of COMT activity was developed and the two approaches are
      discussed. In the presented methods, substrate and reaction products are
      monitored at the same time. The initial velocity of the reaction is quantified
      spectrophotometrically by the corrected peak area of the products at 200 nm. In
      the off-line setup, capillary zone electrophoresis is used to separate and
      quantify the different reaction compounds. Each electrophoretic run required only
      37 nL of the enzymatic reaction solution. Based on the off-line assay, an in-line
      determination of COMT activity was developed by a methodology known as
      electrophoretically mediated microanalysis (EMMA). All the different steps (i.e.
      mixing, incubation, separation and in-line quantitation) are combined in the
      capillary, which is used as a microreactor for the enzymatic reaction. Full
      automation of the assay is achieved with this microscale approach.

PMID- 12007137
TI  - Formation kinetics and stability studies on the lanthanide complexes of 1,4,7,10
      tetraazacyclododecane-N,N',N",N"'-tetraacetic acid by capillary electrophoresis.
AB  - In this study, the kinetic behaviors of four lanthanide ions, Sm(3+), Dy(3+),
      Yb(3+) and Lu(3+), when mixed with a polyazamacrocyclic chelating agent 1,4,7,10
      tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), were investigated by
      capillary electrophoresis (CE) in the pH range of 2.0-6.0. At pH 2.0, the
      formation rate of DOTA-metal complex is extremely low as very little complex was
      detected after 5 days reaction, whereas almost no free DOTA was found in the
      mixture of metal ion and DOTA after 4 min at pH 6.0. The second-order kinetic
      association rate constants of the four lanthanide ions chelates at pH 4.2 were
      calculated as 1.44 x 10(-2) mM(-1)min(-1), 5.20 x 10(-2) mM(-1)min(-1), 4.56 x
      10(-2) mM(-1)min(-1) and 4.54 x 10(-2) mM(-1)min(-1) at 25 degrees C with CE,
      respectively. In addition, the stability constants of the four lanthanide ions
      with DOTA were determined by CE at pH 3.0 where approximately 80-90% of the metal
      ions were associated with DOTA at 25 degrees C. The measured stability constants
      (log K(f)) of the four DOTA-metal complexes were 23.36, 23.93, 23.39 and 23.06,
      respectively, and correlated well with published data obtained by different
      methods. The percentage of metal ion bound with DOTA was evaluated as a function
      of reactant concentration in pH 6.0 buffer. After adding excess strong acid (0.1
      M HCl) to each solution of DOTA-metal was formed at pH 6.0, no released DOTA was
      detected after 24 h; thus, dissociation of these lanthanide complexes did not
      occur under strongly acidic conditions. The Ln(DOTA)(-) species for the four DOTA
      metal complexes were characterized by electrospray ionization-mass spectroscopy
      (ESI-MS), and the results correlated with proposed structures.

PMID- 12007140
TI  - Interleukin-13 and -4 induce death of activated microglia.
AB  - When the brain suffers injury, microglia migrate to the damaged sites and become
      activated. These activated microglia are not detected several days later and the
      mechanisms underlying their disappearance are not well characterized. In this
      study, we demonstrate that interleukin (IL)-13, an anti-inflammatory cytokine,
      selectively induces cell death of activated microglia in vitro. Cell death was
      detected 4 days after the coaddition of IL-13 with any one of the microglial
      activators, lipopolysaccharide (LPS), ganglioside, or thrombin. This cell death
      occurred in a time-dependent manner. LPS, ganglioside, thrombin, or IL-13 alone
      did not induce cell death. Among anti-inflammatory cytokines, IL-4 mimicked the
      effect of IL-13, while TGF-beta did not. Cells treated with IL-13 plus LPS, or IL
      13 plus ganglioside, showed the characteristics of apoptosis when analyzed by
      electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling staining. Electron micrographs also showed microglia engulfing
      neighboring dead cells. We propose that IL-13 and IL-4 induce death of activated
      microglia, and that this process is important for prevention of chronic
      inflammation that can cause tissue damage.

PMID- 12007141
TI  - BK channels in human glioma cells have enhanced calcium sensitivity.
AB  - We have previously demonstrated the expression of large-conductance, calcium
      activated potassium (BK) channels in human glioma cells. In the present study, we
      characterized the calcium sensitivity of glioma BK channels in excised membrane
      patches. Channels in inside-out patches were activated at -60 mV by 2.1 x 10(-6)
      M cytosolic Ca(2+), were highly K(+)-selective, and had a slope conductance of
      approximately iqual 210 pS. We characterized the Ca(2+) sensitivity of these
      channels in detail by isolating BK currents in outside-out patches with different
      free [Ca(2+)](i). The half-maximal voltage for channel activation, V(0.5), of
      glioma BK currents in outside-out patches was +138 mV with 0 Ca(2+)/10 EGTA.
      V(0.5) was shifted to +81 mV and -14 mV with free [Ca(2+)](i) of 1.5 x 10(-7) M
      and 2.1 x 10(-6) M, respectively. These results suggest that glioma BK channels
      have a higher Ca(2+) sensitivity than that described in many other human
      preparations. Data obtained from a cloned BK channel (hbr5) expressed in HEK
      cells support the conclusion that glioma BK channels have an unusually high
      sensitivity to calcium. In addition, the sensitivity of glioma BK channels to the
      BK inhibitor tetrandrine suggests the expression of BK channel auxiliary beta
      subunits by glioma cells. Expression of the auxiliary beta-subunit of BK channels
      by glioma cells may relate to the high Ca(2+) sensitivity of glioma BK channels.

PMID- 12007142
TI  - Astrocyte-derived factors modulate the inhibitory effect of ethanol on dendritic
      development.
AB  - Numerous studies in vivo and in vitro have demonstrated that ethanol disrupts
      neuromorphogenesis. However, it has not been determined what role, if any, is
      played by non-neuronal cells in mediating this effect. We recently reported that
      ethanol inhibits dendritic development in low-density cultures of fetal rat
      hippocampal pyramidal neurons (Yanni and Lindsley, 2000: Dev Brain Res 120:233
      243). In this culture system, cortical astrocytes precondition neuronal culture
      media for 2 days before the addition of neurons, which then develop on a separate
      substrate in coculture with the astrocytes. To determine whether astrocyte
      response to ethanol mediates the effects of ethanol on neurons, the present study
      compared dendritic development of neurons after 6 days in medium containing 400
      mg/dl ethanol in coculture with live astrocytes and in conditioned medium from
      astrocytes that were never exposed to ethanol. The same experiment was also
      performed with and without ethanol present during astrocyte preconditioning of
      the medium. The effects of ethanol differed depending on when it was added to the
      cultures relative to addition of newly dissociated neurons. However, the effects
      of ethanol were not related to whether neurons were cocultured with live
      astrocytes. When astrocytes preconditioned the medium normally, ethanol added at
      plating inhibited dendritic development of neurons regardless of whether they
      were maintained in coculture with live astrocytes or in conditioned medium. In
      surprising contrast, the presence of ethanol during astrocyte preconditioning of
      the media had a growth promoting effect on subsequent dendrite development
      despite the continued presence of ethanol in the medium. Thus, astrocytes release
      soluble factors in response to ethanol that can protect neurons from the
      inhibitory effects of ethanol on dendritic growth, but the timing of neuronal
      exposure to these factors, or their concentration, may influence their activity.

PMID- 12007143
TI  - Platelet-derived growth factor-b expression induced after rat peripheral nerve
      injuries.
AB  - Schwann cells are crucially important for peripheral nerve regeneration. These
      cells synthesize several factors that are supposed to enhance axonal regeneration
      when injured. Platelet-derived growth factor (PDGF) B-chain and its beta-receptor
      are expressed in Schwann cells in both normal peripheral nerves and culture. To
      elucidate the role of PDGF-B in peripheral nerve regeneration, we investigated
      its expression in cut or crush-injured rat sciatic nerves for up to 28 days.
      Northern blotting identified substantial increase of PDGF B-chain transcripts in
      injured nerves. Immunohistochemistry demonstrated that protein products of the
      transcripts were augmented at the distal tip of swollen axons in proximal nerve
      segments and in regenerating axons. Soon after both types of injury, considerable
      amounts of PDGF-B accumulated in numerous Schwann cells in distal segments of
      both models. With restoration of the axon-Schwann cell relationship in the crush
      model, levels of PDGF-B tended to decrease, eventually returning to normal. In
      the cut model in which the relationship cannot be restored, the PDGF-B was
      depleted to a very low level. The spatiotemporal correlation between PDGF-B and
      cell proliferation was very close throughout the study. These results differed
      strikingly from those of our previous study of rat optic nerve transection, in
      which PDGF-B was expressed only in a few recruited macrophages and glial cells.
      Augmented PDGF-B expression after sciatic nerve injury might contribute to
      peripheral nerve regeneration because PDGF-B is a mitogen and survival factor for
      Schwann cells and because it has trophic activity on neurons.

PMID- 12007144
TI  - Proteasome dynamics during cell cycle in rat Schwann cells.
AB  - The proteasome is responsible for most of the protein degradation that takes
      place in the cytoplasm and nucleus. Immunofluorescence and electron microscopy
      are used to study proteasome dynamics during the cell cycle in rat Schwann cells.
      During interphase, the proteasome is present in the nucleus and cytoplasm and
      shows no colocalization with cytoskeletal components. Some cytoplasmic
      proteasomes always localize in the centrosome both in interphase and in mitotic
      cells and only associate with microtubules during mitosis. The proteasome exits
      the nucleus during prophase. In anaphase, the proteasome becomes prominent in the
      region between the two sets of migrating chromosomes and in association with
      interzonal microtubules and stem bodies. In telophase, the proteasome begins to
      reenter the nucleus and is prominent in the midbody region until the end of
      cytokinesis. The proteasome does not colocalize with actin or vimentin during
      mitosis, except for colocalization with actin in the sheet-like lamellipodia,
      which serve as substrate attachments for the cell during mitosis. During S phase,
      nuclear proteasomes colocalize with foci of BrdU incorporation, but this
      association changes with time: maximal at early S phase and declining as S phase
      progresses to the end. These results are discussed in relation to the biochemical
      pathways involved in cell cycle progression.

PMID- 12007145
TI  - Expression and distribution of id helix-loop-helix proteins in human astrocytic
      tumors.
AB  - The Id family of helix-loop-helix proteins is involved in a variety of processes,
      such as development, proliferation, and angiogenesis. In this study, we
      investigated the expression pattern of Id1, Id2, and Id3 in surgical specimens of
      human glial tumors. Western blot analysis demonstrated that all three Id proteins
      were expressed in astrocytic tumors. Expression levels in high-grade tumors were
      higher than in low-grade tumors. Immunohistochemical analysis confirmed that many
      of the tumor astrocytes exhibited strong Id1-3 IR. In contrast, in adult human
      normal brain, Id expression was low both in resting astrocytes and in endothelial
      cells. In tumor cells, Id proteins displayed cytoplasmic as well as nuclear
      localization. Id1-3 IR scores in tumor cells were positively correlated with
      proliferation indices. Moreover, Id1-3 IR was detected in endothelial cells of
      the astrocytic tumor blood vessels. The vascular Id1-3 expression correlated
      positively with tumor vascularity and grade. These results support the role of
      the Id gene family in the enhanced proliferative potential of tumor astrocytes.
      The evidence also supports the involvement of the Id gene family in tumor
      angiogenesis, a process that critically influences the malignant behavior of
      glial tumors.

PMID- 12007146
TI  - Life imaging of peroxynitrite in rat microglial and astroglial cells: Role of
      superoxide and antioxidants.
AB  - Free radicals, such as superoxide and nitric oxide, are known to play a role in a
      number of inflammatory and degenerative brain diseases, in which resident
      microglia upregulate the inducible nitric oxide synthase (iNOS) and thus produce
      large amounts of nitric oxide. Simultaneously, microglia generate superoxide
      mainly via NADPH-oxidase, which reacts at a diffusion-limited rate with nitric
      oxide to form the powerful oxidant peroxynitrite. We used mixed
      astroglial/microglial cultures to study the effects of iNOS induction by
      lipopolysaccharide and interferon-gamma on free radical formation. Using the
      fluorogenic compound 2,7-dihydrodichlorofluorescein diacetate, we monitored
      cellular peroxynitrite formation by confocal laser microscopy. Peroxynitrite
      formation in continuously nitric oxide-producing microglial cells was rather
      limited. However, activation of the superoxide-generating enzyme NADPH-oxidase
      dramatically increased DCF fluorescence within a few minutes. We conclude that
      superoxide is the limiting factor for peroxynitrite formation. Since the
      formation and oxidant activity of peroxynitrite depends strongly on the
      availability of cellular antioxidants, we investigated the capacity of several
      compounds to influence peroxynitrite formation. Among the substances under
      investigation in this study, glutathione and the synthetic compound ebselen had a
      major effect on preventing peroxynitrite formation, whereas ascorbate failed to
      decrease peroxynitrite levels.

PMID- 12007147
TI  - RhoA inhibition is a key step in pituicyte stellation induced by A(1)-type
      adenosine receptor activation.
AB  - Pituicyte stellation in vitro represents a useful model with which to study
      morphological changes that occur in vivo in these cells during times of high
      neurohypophysial hormone output. This model has helped us establish the
      hypothesis of a purinergic regulation of pituicyte morphological plasticity. We
      first show that ATP induces stellation in 37% of pituicytes, an effect that is
      secondary to the metabolism of ATP to adenosine. Adenosine-induced stellation of
      pituicytes appears to be mediated by A(1)-type receptors. The effect is
      independent of intracellular calcium and does not involve the mitogen-activated
      protein kinase pathway. The basal (nonstellate) state of pituicytes depends on
      tonic activation of a Rho GTPase because both C3 transferase (a Rho inhibitor)
      and Y-27632 (an inhibitor of p160Rho kinase) can induce stellation.
      Lysophosphatidic acid, a Rho activator, blocks the morphogenic effect of
      adenosine dose-dependently. Using a specific RhoA pull-down assay, we also show
      that downregulation of activated RhoA is the key event coupling A(1) receptor
      activation to pituicyte stellation, via F-actin depolymerization and microtubule
      reorganization. Finally, both vasopressin and oxytocin can prevent or reverse
      adenosine-induced stellation. The effects of vasopressin, and those of high
      concentrations of oxytocin, are mediated through V(1a) receptors. Placed within
      the context of the relevant literature, our data suggest the possibility of a
      purinergic regulation of pituicyte morphological plasticity and subsequent
      modulation of hormone release, with these hormones providing a negative feedback
      mechanism.

PMID- 12007151
TI  - Responding to society's needs: prescription privileges for psychologists.
AB  - The health care revolution has contributed to the natural evolution of the role
      of psychologists. This has led to the necessity for future psychologists to have
      the authority to prescribe psychotropic medications in order to offer the best
      available, comprehensive treatment to the public. Psychologists' training gives
      them a unique role in addressing the psychosocial aspects of medical problems, in
      collaboration with primary-care physicians. Prescribing psychologists are cost
      effective, many practice in rural areas where people have no other access to
      mental health care, and they will be able to treat other underserved populations
      such as the poor, the elderly, the chronically mentally ill, children, and
      prisoners in the criminal justice system. Prescribing psychologists will have an
      increasingly prominent role in future health care policy decisions and practice.

PMID- 12007148
TI  - Immunohistochemistry study of human vestibular nerve schwannoma differentiation.
AB  - Differentiation of primary human vestibular nerve schwannomas (VS) caused by
      mutations of the NF2 gene was evaluated by examining the expression patterns of
      genes that are specifically expressed in different stages of Schwann cell
      lineage. In schwannoma cells that are not in contact with an axon, the expression
      levels of the major myelin sheath proteins, such as protein zero glycoprotein
      (P0), myelin basic protein (MBP), and peripheral myelin protein 22 (PMP22), were
      greatly reduced. However, high expression levels of nerve growth factor receptor
      (NGFR), neural cell adhesion molecule (N-CAM), and cell adhesion molecule L1 (L1)
      were observed. In addition, expression of transcription factors Krox20, Krox24,
      and SCIP/Oct6 was also detected in the tumor cells. These results suggest that
      loss of the NF2 gene was responsible for the transformation of the Schwann cells
      into a neoplastic stage that has a similar genetic profile to the pro-myelinating
      stage. Finally, the primary human vestibular schwannoma cells failed to be
      regulated and redifferentiated by a regenerating axon, when the human tumors were
      transplanted into sciatic nerve of nude rat. These results suggest that the NF2
      gene might be involved in the differentiation of Schwann cells.

PMID- 12007152
TI  - Training psychologists in clinical psychopharmacology.
AB  - This article first describes three types of psychopharmacology training programs
      for psychologists: 1. postdoctoral programs that award certificates and/or
      continuing education credit; 2. postdoctoral programs that award master's degrees
      in psychopharmacology; 3. a predoctoral program that awards joint psychology and
      nursing degrees. Next, the postdoctoral masters degree program at Nova
      Southeastern University is described in some detail. We close with some general
      comments about the current status of these training efforts.

PMID- 12007153
TI  - The psychologist's role in the collaborative process of psychopharmacology.
AB  - This is a discussion of a collaborative approach between psychologists,
      physicians, patients, and others in the administration of psychotropic
      medication. It is based on a systems point of view. In that perspective, not only
      are the people indicated above a system, but also the patient is considered from
      a holistic-systems point of view. It requires that the psychologist not only be a
      member of the system, and a well-versed in medication member at that; (s)he must
      also be an observer of the system, be able to take a meta perspective, in order
      to be able to exercise some unique functions--functions for which psychologists
      are well-trained.

PMID- 12007154
TI  - Opposition to prescriptive authority: is this a case of the tail wagging the dog?
AB  - This essay proposes that opposition to prescriptive authority (RxP) is not
      grounded in or based on any objective data. Opposition arguments fall into the
      category of ideology, opinion, and inappropriate economic beliefs. Moreover, what
      scant data does exist with respect to prescribing psychologists, the data
      disputes the main arguments in opposition to RxP. Major themes expressed by RxP
      opponents are analyzed, and counter-arguments are presented concluding that RxP
      opposition is not precedent-setting but part of the historical tension between
      academic and applied psychologists. The only precedent may be in the way the
      controversy is resolved.

PMID- 12007155
TI  - Just say no to psychotropic drugs!
AB  - Prescribing drugs for mental disorders by psychologists means accepting an
      invalid model--the brain disease, biological-defect explanation of
      psychopathology--that is advanced by political conservatives and accepted by some
      naive, well-intentioned, but misinformed moderates who have not thought
      critically about the issue. Conservative psychiatry serves the ruling class by
      rejecting or ignoring the fact that most mental disorders are learned in the
      context of social and economic injustice, and familiar dysfunction. If we accept
      the fallacy of brain disease and genetic defect as the major causes of mental
      disorder and succeed in getting prescription privileges we will have sold our
      soul to the devil!

PMID- 12007156
TI  - Preparing psychologists to prescribe.
AB  - In this report, an investigation of the training received by professionals
      currently authorized to prescribe medications is considered as a step toward
      understanding what might be involved in preparing psychologists appropriately if
      prescription privileges for psychology were to be obtained. Information about
      admission and curriculum requirements was collected from medical schools, dental
      schools, physician assistant programs, nurse practitioner programs, and schools
      of optometry. Results suggest a high level of pharmacologically relevant
      coursework is required for admission to, and the completion of, programs that
      currently prepare their professionals to prescribe. It is argued that preparing
      psychologists to prescribe would likely entail similar training requirements in
      addition to, or instead of, those already in place, leaving clinical psychology
      dramatically and permanently altered.

PMID- 12007157
TI  - Training for prescriptions vs. prescriptions for training: where are we now?
      Where should we be? How do we get there?
AB  - The proposal that state legislatures should grant prescription privileges to
      psychologists is examined critically, with particular attention to the proposal's
      implications for the future education and training of clinical psychologists.
      First, the current status of clinical psychology is described. Then, an
      alternative to the prescription privilege proposal is presented; this alternative
      prescribes a scientific approach to clinical psychology. Finally, a plan for
      achieving this alternative is outlined.

PMID- 12007158
TI  - The high cost of prescription privileges.
AB  - This article presents some data regarding the costs in the augmentation of
      programs aimed at equipping psychologist to prescribe medications. Data are
      presented relative to the financial burden it will place on students,
      universities, internship sites, and the consumers of psychological services.

PMID- 12007159
TI  - Prescribing privileges: grail for some practitioners, potential calamity for
      interprofessional collaboration in mental health.
AB  - The focus of this article is the probable consequences, in the event
      psychologists aggressively pursue prescription privileges (RxP), upon
      collaboration between psychologists and physicians. The case for RxP is briefly
      and critically summarized and the current state of collaboration between
      psychologists and medical professionals is reviewed. Data are presented from a
      recent small survey of clinical psychologists that support the following
      hypotheses: (1) psychiatrists and other medical professional receive a
      consequential volume of referrals from psychologists which would be diminished by
      RxP; (2) psychologists receive referrals for psychosocial services from medical
      professionals which would be diminished by RxP; (3) psychologists anticipate an
      adverse effect upon collaboration from RxP; and (4) contrary to some claims,
      psychologists are at best divided over RxP. Implications of these findings upon
      interprofessional collaboration are discussed.

PMID- 12007160
TI  - Prescription privileges for psychologists: constituencies and conflicts.
AB  - The pros and cons of the proposal to link prescription privileges specifically to
      psychological training vary from the point of view of the constituencies
      involved. The present article analyzes those differences. Two surprising facts
      are noted. First, it is scientist-practitioners who are resisting the move toward
      prescription privileges, not so much the basic science organizations. Second,
      while the practice-based organizations have been avid in their support of
      prescription privileges, the same cannot be said for rank and file private
      practitioners. On closer examination, the costs, benefits, and views of the
      different constituencies make sense of these anomalies. The resistance to
      prescription privileges is not arbitrary or unreasonable and it is not likely to
      go away any time soon.

PMID- 12007161
TI  - Concluding remarks on the debate about prescription privileges for psychologists.
AB  - This article summarizes the six primary arguments for and against prescription
      privileges for psychologists (PPP or RxP) that were presented in this special
      issue. Four articles addressed points made in the testimony in favor of PPP by
      the American Psychological Association. Six articles addressed points in the
      testimony against PPP by the American Association of Applied and Preventive
      Psychology. It is concluded that the PPP debate reflects a deep schism in
      clinical psychology that represents a serious disunity in the field. The disunity
      is seen as a divide between those trained to be psychotherapists and those
      trained to be scientist-practitioners. It is argued that the former support PPP
      and are interested in the survival of professional schools, while the latter
      oppose PPP and are interested in the survival of university departments of
      psychology. For the discipline to survive there must be a rapprochement between
      these factions and alternatives to PPP for the retraining of psychotherapy
      practitioners.

PMID- 12007162
TI  - Prenatal screening for cystic fibrosis: an economic analysis.
AB  - Cystic fibrosis (CF) is the most common life-shortening genetically transmitted
      disease in Denmark with a birth prevalence of 1 in 4700, resulting in 12-15 new
      cases of cystic fibroses annually. The aim of this study is to disclose the
      societal resource implications of introducing a population wide prenatal
      screening programme for cystic fibrosis in Denmark. The present analysis is
      limited to the monetary consequences of introducing a screening programme, where
      costs of screening are compared to the potential benefits measured in cost
      savings involved if births of CF patients are avoided. Screening costs in a
      Danish setting were estimated at DKK 2 771 262 ( pound sterlings 231 438) per
      aborted affected fetus in the first screening round, stabilising at DKK 1 864 594
      ( pound sterlings 155 383) per aborted affected fetus at subsequent screening
      rounds. Comparing this figure with the estimated benefits of avoiding a CF case
      (DKK 2.1-4.4 million; pound sterlings 175 000-366 667) suggests that introducing
      a screening programme for cystic fibrosis will be net cost saving irrespective of
      the perspective of the analysis, assumptions on replacement children and method
      of estimating long-term production gains/losses.

PMID- 12007163
TI  - Latent class versus two-part models in the demand for physician services across
      the European Union.
AB  - Using three waves of data from the European Community Household Panel, this paper
      estimates demand for physician services equations for 12 European countries. We
      focus on the selection of the most appropriate econometric specification for
      visits to general practitioners and to specialists among two-part and latent
      class models. The distinction between the demand of services from these two types
      of physicians allows us to distinguish cases in which two-part perform better
      than latent class models, evidence which is different from previous findings in
      the literature. The results suggest that latent class models are more appropriate
      than two-part models to estimate general practitioners utilisation while the
      opposite is found for visits to the specialists.

PMID- 12007164
TI  - Do Medicare HMOs still reduce health services use after controlling for selection
      bias?
AB  - This study models the relationship between Medicare beneficiary decisions to join
      Medicare HMOs and subsequent health services utilization. The relationship
      between health plan choice and utilization is thought to be endogenous because of
      favorable selection into HMOs. Previous studies found significantly lower
      inpatient utilization among Medicare HMO enrollees than among nonenrollees, but
      lacked strong controls for selection bias. Thus, a firm conclusion could not be
      drawn as to whether the observed differences were attributable to the HMO
      practice setting or to baseline differences in the illness profiles of the two
      groups studied. The present study uses simultaneous equations methods, including
      discrete factor estimation, to test the effect of Medicare HMOs on utilization
      when strong controls for selection bias are imposed. The model was run on a panel
      of 1993-1996 data from the Medicare Current Beneficiary Survey, supplemented with
      linked data on Medicare HMO characteristics and area supply characteristics. The
      study found that even when favorable selection is controlled for, Medicare HMOs
      significantly reduce both the probability of hospitalization and the number of
      inpatient days used by those who are hospitalized. Medicare HMOs do not, however,
      appear to reduce the use of physician services.

PMID- 12007165
TI  - Estimating an EQ-5D population value set: the case of Japan.
AB  - Quality adjustment weights for quality-adjusted life years (QALYs) are available
      with the EQ-5D Instrument, which are based on a survey that quantified the
      preferences of the British public. However, the extent to which this British
      value set is applicable to other, especially non-European, countries is yet
      unclear. The objectives of this study are (a) to compare the valuations obtained
      in Japan and Britain, and (b) to explore a local Japanese value set. A diminished
      study design is employed, where 17 hypothetical EQ-5D health states are evaluated
      as opposed to 42 in the British study. The official Japanese version of the
      instrument and the Time Trade-Off method are used to interview 543 members of the
      public. The results are: firstly, the evaluations obtained in Japan and those
      from Britain differ by 0.24 on average on a [-1, +1] scale, and mean absolute
      error (MAE) in predicting the Japanese preferences with the British value set is
      0.23. Secondly, comparable regressions suggest that the two peoples have
      systematically different preference structures (p<0.001 for 8 of 12 coefficients;
      F-test). Thirdly, using alternative models, the predictions are improved so that
      the local Japanese value set achieves MAE in the order of 0.01.

PMID- 12007166
TI  - Discounting and clinical decision making: physicians, patients, the general
      public, and the management of asymptomatic abdominal aortic aneurysms.
AB  - Clinical decisions often entail in intertemporal trade-off. Moreover, they often
      involve physicians of different specialities. In an experiment dealing with the
      management of small asymptomatic abdominal aortic aneurysms (a clinically
      relevant problem) we find that specialists in internal medicine exhibit higher
      implicit discount rates than vascular surgeons, general practitioners, and actual
      and prospective patients. Several personal characteristics expected to be
      directly related to pure time-preference and risk aversion (gender, smoking
      habits, age, place of employment) have the hypothesised effects. Additionally,
      financial incentives appear to affect the estimated implicit discount rates of
      physicians, but are unlikely to have caused the inter-group differences.
      Differences in discount rates could lead to variations in clinical practice,
      which may conflict with equality of treatment or equal access to health care.

PMID- 12007167
TI  - Unit root properties of OECD health care expenditure and GDP data.
AB  - This note reconsiders the unit root properties of health care expenditure (HCE)
      and gross domestic product (GDP) for OECD countries. The time-series properties
      of this data set has been much discussed in the literature with contrasting
      results from the application of a range of test procedures. We use a recently
      developed test to examine the relationship between the two variables. The results
      in this paper confirm earlier findings that when the data are considered as a
      panel, there is strong evidence of unit roots in both GDP and HCE data.

PMID- 12007171
TI  - Body shaping under water stress: osmosensing and osmoregulation of solute
      transport in bacteria.
AB  - Fluctuation of external osmolarity is one of the most common types of
      environmental stress factors for all kind of cells, both of prokaryotic and of
      eukaryotic origin. Cells try to keep their volume and/or turgor pressure
      constant; consequently, both a decrease (hypoosmotic stress) and an increase
      (hyperosmotic stress) of the solute concentration (correctly: increase or
      decrease in water activity) in the surrounding area, respectively, are challenges
      for cellular metabolism and survival. A common example from the prokaryotic world
      is the fate of a soil bacterium that, after a sunny day has dried out the soil
      (hyperosmotic stress), is suddenly exposed to a drop of distilled water from a
      rain cloud (hypoosmotic stress). The immediate and inevitable passive response to
      the sudden osmotic shift in the surroundings is fast water efflux out of the cell
      in the former situation and water influx in the latter. In the worst case, these
      responses may lead to either loss of cell turgor and plasmolysis or to cell
      burst. In order to overcome such drastic consequences cells have developed
      effective mechanisms, namely osmoadaptation, to cope with the two different types
      of osmotic stress. For a graded reaction to osmotic shifts, cells must be able
      (1) to sense stimuli related to osmotic stress, (2) to transduce corresponding
      signals to those systems that properly respond (3) by activating transport or
      enzymatic functions or (4) by changing gene expression profiles. In this review,
      membrane proteins involved in the cell's active response to osmotic stress are
      described. Molecular details of structure, function, and regulation of
      mechanosensitive efflux channels from various organisms, as well as of
      osmoregulated uptake systems are discussed.

PMID- 12007172
TI  - Combining chemical and biological techniques to produce modified proteins.

PMID- 12007173
TI  - Molecular insights into error-prone DNA replication and error-free lesion bypass.

PMID- 12007174
TI  - Giant vesicles as microreactors for enzymatic mRNA synthesis.
AB  - Giant vesicles have attracted much attention as possible microreactors for the
      conduction of enzymatic reactions in an artificial, cell-sized compartment. In
      this context, we demonstrated in the first part of the present work that giant
      vesicles formed from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine in an
      alternating electric field can be made more permeable to Ca(2+) ions or
      nucleotide triphosphates by addition of ethanol. This methodology is then applied
      in a second step whereby these giant vesicles are used as microreactors in which
      mRNA synthesis can occur. The macromolecules (the DNA template and the enzyme T7
      RNA polymerase) are microinjected into a selected giant vesicle, while the
      substrate molecules (nucleotide triphosphates) are added from the external
      medium. The fact that mRNA synthesis can be detected is a further step towards
      our aim: the design of a microreactor that can be seen as a model for a
      protocell.

PMID- 12007175
TI  - Synthesis of ferroquine enantiomers: first investigation of effects of
      metallocenic chirality upon antimalarial activity and cytotoxicity.
AB  - Ferroquine (FQ) is a new antimalarial agent with a high blood schizotoncidal
      activity. Previous studies on this compound were done with racemate mixtures. As
      FQ possesses planar chirality, pure enantiomers were obtained by enzymatic
      resolution in order to compare their antimalarial activities and cytotoxicities.
      (+)-FQ and (-)-FQ were equally active in vitro, at nanomolar concentrations. Both
      enantiomers were slightly less active than the racemate in vivo; cytotoxicities
      were similar. Actually, the racemate represents the optimal formulation. To the
      best of our knowledge, this is the first investigation of biological activities
      of compounds with metallocenic chirality.

PMID- 12007176
TI  - On the biodegradation of beta-peptides.
AB  - A consortium of microorganisms was established that was able to grow with the
      beta-tripeptide H-beta-HVal-beta-HAla-beta-HLeu-OH, with the beta-dipeptide H
      beta-HAla-beta-HLeu-OH, and with the beta-amino acids H-beta-HAla-OH, H-beta-HVal
      OH, and H-beta-HLeu-OH as the sole carbon and energy sources. This growth was
      achieved after several incubation-transfer cycles with the beta-tripeptide as the
      substrate. During degradation of the beta-tripeptide H-beta-HVal-beta-HAla-beta
      HLeu-OH, the temporary formation of a metabolite was observed. The metabolite was
      identified as the beta-dipeptide H-beta-HAla-beta-HLeu-OH by nuclear magnetic
      resonance spectroscopy and mass spectrometry. This result indicates that in the
      course of the degradation of the beta-tripeptide, the N-terminal beta-HVal
      residue was cleaved off by a not yet known mechanism. During the subsequent
      degradation of the beta-dipeptide, formation of additional metabolites could not
      be detected. The growth-yield coefficients Y(x/s) for growth on the beta-di- and
      beta-tripeptide both had a value of 0.45. When a 1:1 mixture of the beta
      tripeptide and the corresponding alpha-tripeptide H-Val-Ala-Leu-OH was added to
      the enrichment culture, the alpha-peptide was completely utilized in six days and
      thereafter growth of the culture stopped. This result indicates that even in beta
      peptide enrichment cultures, alpha-peptides are the preferred substrates. Our
      experiments clearly show for the first time that beta-peptides and beta-amino
      acids are amenable to biodegradation and that a microbial consortium was able to
      utilize these compounds as sole carbon and energy sources. Furthermore, the
      preparation of beta-amino acids, of derivatives thereof, and of beta-di- and beta
      tripeptides is described.

PMID- 12007177
TI  - New dendrimer-peptide host-guest complexes: towards dendrimers as peptide
      carriers.
AB  - Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers
      act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form
      chloroform-soluble complexes. Investigations with NMR spectroscopy show that the
      peptide is bound to the dendrimer by ionic interactions between the dendrimer
      outer shell tertiary amines and the C-terminal carboxylic acid of the peptide,
      and also through host-urea to peptide-amide hydrogen bonding. The hydrogen
      bonding nature of the peptide-dendrimer interactions was further confirmed by
      using Fourier transform IR spectroscopy, for which the NH- and CO-stretch signals
      of the peptide amide moieties shift towards lower wavenumbers upon complexation
      with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy
      generally shows close proximity of the N-terminal Boc group of the peptide to the
      peripheral adamantyl groups on the dendrimer host. The influence of side-chain
      motif on interactions with the host is analyzed by using seven different N-Boc
      protected tripeptides as guests for the dendrimer. Downfield shifts of up to 1.3
      ppm were observed for the guest amide NH-proton signals. These shifts decreased
      with increasing 'bulkiness' of the amino acid side chains. Despite this, the
      dendrimer was capable of making multiple peptide-dendrimer complexes when
      presented with a library of seven peptides. The different peptides were all
      present in the host, which did not show specific preferences, and could be
      released under mild acidic conditions. These results show the general nature of
      the peptide-dendrimer interactions in the formation of either single- or multiple
      peptide-dendrimer complexes.

PMID- 12007178
TI  - Biomimetic studies on iodothyronine deiodinase intermediates: modeling the
      reduction of selenenyl iodide by thiols.
AB  - Enzyme mimetic studies on the crucial intermediate (E-SeI) of the iodothyronine
      deiodinase cycle have been carried out by using an areneselenenyl iodide
      stabilized by intramolecular Se.N interactions. Treatment of this compound with
      aromatic thiols and thiobenzoxazole in the presence of NEt(3) affords
      areneselenenyl sulfides that are stable towards disproportionation reactions. The
      structures of three of the areneselenenyl sulfides were determined by X-ray
      crystallography. In one case, in the absence of NEt(3), a diselenide can be
      formed rather than the selenenyl sulfide. The areneselenenyl iodide also reacts
      with a related selenol to produce the corresponding diselenide, and this reaction
      is found to be much faster than that with thiols. The high reactivity of the
      selenenyl iodide with the selenol suggests that a reduced selenol group (R'-SeH)
      may react with the E-SeI intermediate to produce a diselenide (E-Se-Se-R')
      without any thiol cosubstrate. The intermediacy of selenenyl sulfides during the
      reduction of selenenyl iodide by thiols and its possible relevance to the
      iodothyronine deiodinase catalytic cycle is also described.

PMID- 12007179
TI  - Enantioselective binding and stable encapsulation of alpha-amino aids in a
      helical poly(L-glutamic acid)-shelled dendrimer in aqueous solutions.
AB  - A novel water-soluble peptide-shelled dendrimer containing a poly(L-glutamic
      acid) segment grafted on the third-generation poly(amido amine) dendrimer was
      successfully synthesized, and its secondary structural properties and interaction
      with alpha-amino acids (Trp, Phe, and Tyr) were revealed by spectroscopic
      measurements. In the lower pH region, this peptide-dendrimer adopted an alpha
      helix conformation with almost 100 % helicity resulting from the three
      dimensional aggregation of the segment. Interactions with alpha-amino acids
      proceeded with positive cooperativity on the basis of a Hill plot, and as a
      result, D isomers preferentially bound to the alpha-helical segments relative to
      L isomers. The bound alpha-amino acids were not released into the water phase but
      were transferred into the inner core of the dendrimer where they remained stable,
      even when a conformational change of the helix segment was caused by pH
      variation.

PMID- 12007180
TI  - A virtual screening method for prediction of the HERG potassium channel liability
      of compound libraries.
AB  - A computer-based method has been developed for prediction of the hERG (human
      ether-a-go-go related gene) K(+)-channel affinity of low molecular weight
      compounds. hERG channel blockage is a major concern in drug design, as such
      blocking agents can cause sudden cardiac death. Various techniques were applied
      to finding appropriate molecular descriptors for modeling structure-activity
      relationships: substructure analysis, self-organizing maps (SOM), principal
      component analysis (PCA), partial least squares fitting (PLS), and supervised
      neural networks. The most accurate prediction system was based on an artificial
      neural network. In a validation study, 93 % of the nonblocking agents and 71 % of
      the hERG channel blockers were correctly classified. This virtual screening
      method can be used for general compound-library shaping and combinatorial library
      design.

PMID- 12007181
TI  - Extracellular synthesis of gold nanoparticles by the fungus Fusarium oxysporum.

PMID- 12007182
TI  - OmpA membrane domain as a tight-binding anchor for lipid bilayers.

PMID- 12007183
TI  - An efficient combinatorial method for the discovery of glycosidase inhibitors.

PMID- 12007184
TI  - A three-state mechanism of integrin activation and signal transduction for
      integrin alpha(v)beta(3).

PMID- 12007186
TI  - Cadherin and catenin alterations in human cancer.
AB  - Among the hallmarks of cancer are defective cell-cell and cell-matrix adhesion.
      Alterations in cadherin-catenin complexes likely have a major contributing role
      in cell-adhesion defects in carcinomas arising in many different tissues. E
      cadherin, the prototypic member of the cadherin transmembrane protein family,
      regulates cell adhesion by interacting with E-cadherin molecules on opposing cell
      surfaces. E-cadherin's function in cell adhesion is also critically dependent on
      its ability to interact through its cytoplasmic domain with catenin proteins. A
      diverse collection of defects alter cadherin-catenin function in cancer cells,
      including loss-of-function mutations and defects in the expression of E-cadherin
      and certain catenins, such as alpha-catenin. Although there is much evidence that
      beta-catenin is deregulated in cancer as a result of inactivating mutations in
      the APC and AXIN tumor-suppressor proteins and gain-of-function mutations in beta
      catenin itself, the principal consequences of beta-catenin deregulation in cancer
      appear to be largely distinct from the effects attributable to inactivation of E
      cadherin or alpha-catenin. In this review, we highlight some of the specific
      genetic and epigenetic defects responsible for altered cadherin and catenin
      function in cancer, as well as potential contributions of cadherin-catenin
      alterations to the cancer process.

PMID- 12007187
TI  - Amplification of the telomerase reverse transcriptase (hTERT) gene in cervical
      carcinomas.
AB  - The expression of telomerase reverse transcriptase (hTERT), the catalytic
      component of the telomerase complex, is required for activation of telomerase
      during immortalization and transformation of human cells. However, the
      biochemical and genetic mechanisms governing hTERT expression remain to be
      elucidated. In the present study, we examined hTERT amplification as a potential
      genetic event contributing to telomerase activation in cervical carcinomas. An
      amplification of the hTERT gene was found in 1/4 cervical cancer cell lines and
      21/88 primary tumor samples derived from the patients with cervical carcinomas.
      An increase in the hTERT copy number was significantly correlated with higher
      levels of hTERT protein expression. Moreover, the hTERT alterations with the
      enhanced hTERT expression were exclusively observed in those tumors with high
      risk human papillomavirus infection. Taken together, the hTERT gene
      amplification, directly or indirectly targeted by human papillomavirus, may be
      one of the driving forces responsible for upregulation of hTERT expression and
      activation of telomerase in cervical cancers.

PMID- 12007188
TI  - Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related
      to chromosomal genomic instability.
AB  - To account for the accumulation of genomic alterations required for tumor
      progression, it has been suggested that the genomes of cancer cells are unstable
      and that this instability results from defective mutators (the "mutator
      phenotype" theory). To examine the hypothesis that abnormal cell-cycle regulators
      act as the mutators contributing to genomic instability, the present study, based
      on primary tumor tissues from 71 patients with breast cancer, was performed to
      determine whether there was an association between aberrant expression of cell
      cycle regulators (cyclin A, cyclin D1, cyclin E, RB1, p21, and p27) and
      chromosomal instability. Comparative genomic hybridization was used to measure
      chromosomal changes, reflecting genomic instability in individual tumors, whereas
      immunohistochemistry was used to detect aberrant expression of cell-cycle
      regulators. Overexpression of cyclin D1 was found to be significantly correlated
      with increased chromosomal instability (defined as harboring more than 7
      chromosomal changes), with 63% of tumors overexpressing and 27% of tumors not
      overexpressing, with cyclin D1 showing chromosomal instability (P < 0.05).
      Interestingly, this relationship was independent of cell outgrowth (as detected
      by the proliferation marker Ki-67) and was particularly significant in tumors not
      expressing p27 or in tumors with detectable RB1. These results suggest that
      cyclin D1 plays an alternative role in the regulation of genomic stability.

PMID- 12007189
TI  - The cancer-related protein SSX2 interacts with the human homologue of a Ras-like
      GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP.
AB  - The SSX gene family is composed of at least five functional and highly homologous
      members, SSX1 to SSX5, that are normally expressed in only the testis and
      thyroid. SSX1, SSX2, or SSX4 may be fused to the SYT gene as a result of the
      t(X;18) translocation in synovial sarcoma. In addition, the SSX1, SSX2, SSX4, and
      SSX5 genes were found to be aberrantly expressed in several other malignancies,
      including melanoma. The SSX proteins are localized in the nucleus and are
      diffusely distributed. In addition, they may be included in polycomb-group
      nuclear bodies. Other studies have indicated that the SSX proteins may act as
      transcriptional repressors. As a first step toward the elucidation of the
      cellular signaling networks in which the SSX proteins may act, we used the yeast
      two-hybrid system to identify SSX2-interacting proteins. By doing so, two novel
      human proteins were detected: RAB3IP, the human homolog of an interactor of the
      Ras-like GTPase Rab3A; and a novel protein, SSX2IP. RAB3IP did not interact with
      either SSX1, SSX3, or SSX4 in the yeast two-hybrid system, whereas SSX2IP
      interacted with SSX3 but not with either SSX1 or SSX4. Further analysis of
      deletion mutants showed that both RAB3IP and SSX2IP interact with the N-terminal
      moiety of the SSX2 protein. Immunofluorescence analyses of transfected cells
      revealed that the RAB3IP protein is normally localized in the cytoplasm. However,
      coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in
      the nucleus. Likewise, the SSX2IP protein was found to be colocalizing with SSX2
      in the nucleus. By performing glutathione-S-transferase pull-down assays, we
      found that both RAB3IP and SSX2IP interact directly with SSX2 in vitro. These
      newly observed protein/protein interactions may have important implications for
      the mechanisms underlying normal and malignant cellular growth.

PMID- 12007190
TI  - Fluorescence in situ hybridization analyses of chromosome band 1p36 in
      neuroblastoma detect two classes of alterations.
AB  - Chromosomal alterations in 1p36 were investigated in 196 neuroblastoma tumors
      using fluorescence in situ hybridization. Additionally, by using the same
      technique, it was determined whether MYCN was amplified in 149 of these. The most
      frequent finding was a deletion in 1p36, leading to monosomy of this region (29
      cases, 15%). Furthermore, we found tumors with at least two intact copies of
      chromosome 1 and additional 1p36-deleted copies. Altogether, 21 tumors (11%)
      displayed this imbalance of 1p36. Similar to the cases with deletion, imbalances
      were predominantly found in stage 4 tumors (81%), and they were significantly
      associated with an increased patient age (P = 0.01). Nearly all 1p-deleted tumors
      showed amplification of MYCN (24/27 analyzed samples, 89%), whereas only 8 of 21
      (38%) with imbalance did. Eight cases with imbalance were investigated for loss
      of heterozygosity (LOH) using microsatellite markers in 1p35-36. Only 4 displayed
      1p36 LOH, whereas the remaining 4 were heterozygous. Both patients with deletion
      of 1p and with imbalance had a poor outcome [3-year rate of event-free-survival
      (EFS): 33 +/- 15% and 41 +/- 15%], which was significantly worse compared to the
      outcome of patients without 1p alterations (3-year EFS: 70 +/- 5%; P = 0.01 and P
      = 0.0059). We conclude that besides monosomic short arm deletions, imbalance of
      1p36 is a strong marker of a poor prognosis in neuroblastoma and not necessarily
      associated with MYCN amplification and LOH.

PMID- 12007191
TI  - Defining the region(s) of deletion at 6q16-q22 in human prostate cancer.
AB  - Deletion of the long arm of chromosome 6 (6q) frequently occurs in many
      neoplasms, including carcinomas of the prostate and breast and melanoma,
      suggesting the location of a tumor-suppressor gene or genes at 6q. At present,
      however, the region of deletion has not been well defined, and the target gene of
      deletion remains to be identified. In this study, we analyzed 44 primary prostate
      cancers with 16 polymorphic markers for loss of heterozygosity (LOH) by using PCR
      based techniques. We also examined 23 cell lines/xenografts of prostate cancer
      with 38 markers for LOH by the method of homozygosity mapping of deletion. LOH at
      6q16 - q22 was detected in 21 of 44 (48%) primary tumors and in 12 of 23 (52%)
      cell lines/xenografts. Two regions of LOH were defined. One was 7.5 cM at 6q16 -
      q21 between markers D6S1716 and D6S1580, and the other was 4.3 cM at 6q22 between
      D6S261 and D6S1702. Whereas no correlation was found between LOH at 6q16-q22 and
      patient age at diagnosis or Gleason score, tumors at higher stage appear to have
      more frequent LOH. These findings suggest that deletion of 6q16 - q22 is a
      frequent event in prostate cancer, and that the deletion originates from two
      distinct regions. These results should be useful in identifying the target
      gene(s) of deletion at 6q.

PMID- 12007192
TI  - Distinct cytogenetic pathways of advanced-stage neuroblastoma tumors, detected by
      spectral karyotyping.
AB  - Molecular studies of advanced-stage neuroblastoma (NBL) have revealed a marked
      genetic heterogeneity. In addition to MYCN amplification and chromosome 1 short
      arm deletions/translocations detected by conventional cytogenetics, application
      of fluorescence in situ hybridization has disclosed a high prevalence of 17q
      gain, whereas allelotyping and comparative genomic hybridization techniques also
      have revealed loss of 11q and of other chromosomal material. Using the recently
      developed technique of spectral karyotyping (SKY), we sought to refine the
      cytogenetic information, identify hidden recurrent structural chromosomal
      abnormalities, and compare them to the molecular findings. Thirteen samples of
      metaphase spreads from 11 patients with advanced-stage NBL were analyzed by SKY.
      Most of them were found to have complex karyotypes (more than three changes per
      metaphase) and complex unbalanced rearrangements. Recurrent aberrations leading
      to 17q gain, deletion of 1p, MYCN amplification, and loss of 11q appeared in 7,
      4, 4, and 5 patients, respectively, in simple and complex karyotypes. Chromosome
      3 changes and gain of 1q and 7q appeared in 6, 5, and 4 patients, respectively,
      in complex karyotypes only, reflecting later changes. A strikingly high
      prevalence of the unbalanced translocation der(11)t(11;17), leading to
      concomitant 11q loss and 17q gain in 4 patients, delineated a distinct
      cytogenetic group, none having 1p deletion and/or MYCN amplification.
      der(11)t(11;17) was associated with complex karyotypes with changes in
      chromosomes 3 and 7q. The 17q translocations with partners other than 11q were
      associated with 1p deletion and/or MYCN amplification. The distinct cytogenetic
      subgroups identified by SKY confirm and extend the recent molecular observations,
      and suggest that different genes may interact in the der(11)t(11;17) pathway of
      NBL development and progression.

PMID- 12007193
TI  - Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas,
      pheochromocytomas, and abdominal paragangliomas.
AB  - Several types of endocrine tumors show frequent somatic deletions of the distal
      part of chromosome arm 11q, where the tumor-suppressor gene SDHD (succinate
      ubiquinone oxidoreductase subunit D), constitutionally mutated in paragangliomas
      of the head and neck, is located. In this study, we screened 18 midgut
      carcinoids, 7 Merkel cell carcinomas, 46 adrenal pheochromocytomas (37 sporadic
      and 9 familial), and 7 abdominal paragangliomas for loss of heterozygosity (LOH)
      and/or mutations at the SDHD gene locus. LOH was detected in 5 out of 8 (62%)
      informative midgut carcinoids, in 9 out of 30 (30%) sporadic pheochromocytomas,
      in none of the familial pheochromocytomas (0%), and in 1 out of 6 (17%) abdominal
      paragangliomas. No sequence variants were detected in the pheochromocytomas or
      paragangliomas. However, two constitutional putative missense mutations, H50R and
      G12S, were detected in two midgut carcinoids, which were both associated with LOH
      of the other allele. The same sequence variants were also detected in two Merkel
      cell carcinomas. In addition, the S68S polymorphism was found to coexist with the
      G12S sequence variant in both cases. In conclusion, we show that alterations of
      the SDHD gene seem to be involved in the tumorigenesis of both midgut carcinoids
      and Merkel cell carcinomas.

PMID- 12007194
TI  - Direct correlation between FRA3B expression and cigarette smoking.
AB  - Cytogenetic deletions and/or loss of heterozygosity (LOH) of the short arm of
      chromosome 3, often with a break at 3p14, are well documented in lung tumors. The
      coincidence of a chromosomal fragile site, FRA3B, at a common chromosomal
      breakpoint in lung cancer has suggested that fragility at this site may
      predispose to breakage that could contribute to multistep carcinogenesis. This
      idea is supported by the more recent finding that FRA3B maps within the FHIT
      (fragile histadine triad) gene, and that aberrant transcripts and genomic
      deletions of FHIT/FRA3B occur in a variety of tumors including lung tumors. To
      determine whether some individuals have increased fragility of FRA3B that might
      increase the risk for breakage or deletion in 3p14.2, fragile site expression was
      examined in smokers, nonsmokers, and small cell lung cancer (SCLC) patients. The
      data clearly show that active smokers exhibit a significantly higher frequency of
      fragile site expression, including FRA3B, compared to that of nonsmokers and
      patients diagnosed with SCLC who have stopped smoking. These results suggest that
      active tobacco exposure increases chromosome fragile site expression, and that
      this fragility is transient and reversible. The data support the hypothesis that
      exposure to tobacco carcinogens increases the potential for chromosome breakage
      at fragile sites.

PMID- 12007195
TI  - The microcell hybrid-based "elimination test" identifies a 1-Mb putative tumor
      suppressor region at 3p22.2-p22.1 centromeric to the homozygous deletion region
      detected in lung cancer.
AB  - We have previously shown that inoculation of human chromosome 3 (chr3)/A9 mouse
      fibrosarcoma microcell hybrids (MCHs) into severely combined immunodeficient
      (SCID) mice was followed by the regular elimination of certain 3p regions,
      whereas a 3q region was retained even after prolonged mouse passage. Using this
      approach, referred to as the elimination test (Et), we identified a common
      eliminated region (CER) of about 7 cM at 3p22-p21.3 that was absent in all tumors
      generated from five MCHs. A second frequently eliminated region (FER, originally
      called ER2) was found at 3p21.1-p14.2. These segments have been reported to be
      frequently deleted in a variety of carcinomas. In the following experiments, we
      have identified at the centromeric border of CER a common eliminated region 1
      (CER1) of about 1.6 cM. We now report the results of more detailed analyses of
      the original tumor panel that contained 30 SCID mouse tumors. Using polymerase
      chain reaction and chromosome reverse painting, we have identified at the
      telomeric border of CER a second common eliminated region (designated as CER2).
      CER2 is flanked distally by RH94338 and proximally by SHGC-154057. The size of
      CER2 is about 1 Mb, according to the Homo Sapiens Complete Genome databases at
      EMBL, and is located about 0.5 Mb centromeric to the known homozygous deletion
      region, identified in lung cancer. Remarkably, two chemokine-receptor genes
      (CCRs), CCR8 and CX3CR1, are located within CER2, whereas seven CCRs were found
      within CER1.

PMID- 12007196
TI  - Cryopreserved chronic lymphocytic leukemia cells analyzed by multicolor
      fluorescence in situ hybridization after optimized mitogen stimulation.
AB  - We investigated the utility of multicolor in situ fluorescence hybridization
      (mFISH) on cryopreserved blood cells from 11 chronic lymphocytic leukemia (CLL)
      patients. The results demonstrate that an individually chosen optimized mitogen
      combination induces proliferation of neoplastic B-cells after cryopreservation.
      Abnormal cells were detected in eight samples by mFISH, and, in six samples, the
      abnormality could be verified by comparative genomic hybridization or interphase
      FISH. In addition to typical CLL abnormalities, such as del(11q) or +12, several
      balanced translocations and single-cell abnormalities were found. Thus, mFISH can
      reveal new prognostically relevant chromosome aberrations in CLL.

PMID- 12007197
TI  - In vivo evaluation of a dexamethasone/PLGA microsphere system designed to
      suppress the inflammatory tissue response to implantable medical devices.
AB  - The purpose of this research effort was to evaluate in vivo a newly developed
      dexamethasone/PLGA microsphere system designed to suppress the inflammatory
      tissue response to an implanted device, in this case a biosensor. The
      microspheres were prepared using an oil/water (O/W) emulsion technique. The
      microsphere system was composed of drug-loaded microspheres (including newly
      formulated and predegraded microspheres) and free dexamethasone. The combination
      of the drug and drug-loaded microspheres provided burst release of dexamethasone
      followed by continuous release from days 2-14. Continuous release to at least 30
      days was achieved by mixing predegraded and newly formulated microspheres. The
      ability of our mixed microsphere system to control tissue reactions to an implant
      then was tested in vivo using cotton thread sutures to induce inflammation
      subcutaneously in Sprague-Dawley rats. Two different in vivo studies were
      performed, the first to find the dosage level of dexamethasone that effectively
      would suppress the acute inflammatory reaction and the second to show how
      effective the dexamethasone delivered by PLGA microspheres was in suppressing
      chronic inflammatory response to an implant. The first in vivo study showed that
      0.1 to 0.8 mg of dexamethasone at the site minimized the acute inflammatory
      reaction. The second in vivo study showed that our mixed microsphere system
      suppressed the inflammatory response to an implanted suture for at least 1 month.
      This study has proven the viability of microsphere delivery of an anti
      inflammatory to control the inflammatory reaction at an implant site.

PMID- 12007198
TI  - Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly (D,L-lactic
      acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition
      in water.
AB  - Novel thermoreversible gelation behavior of aqueous solutions of ABA-type
      triblock copolymers composed of the central polyethylene oxide (PEG) block and
      two poly(D,L-lactic acid-co-glycolic acid) side blocks was found. Phase
      transition characteristics, such as critical gel concentration (CGC) and lower
      and upper critical gel temperature (CGT), are closely related to the molecular
      structure of the triblock copolymers. The CGC and the lower CGT both increases
      with increasing PEG/PLGA molecular weight ratio. Increasing the GA content in
      PLGA block induces a somewhat higher CGC. The copolymer forms micelles with a
      PLGA loop core and a PEG shell in water. Also grouped micelles are identified
      seemingly due to the bridging of two micelles sharing two PLGA blocks of a block
      copolymer chain. As the temperature increases the association of micelles
      increases, which results in gelation. The ABA-type copolymers exhibit a
      relatively low CGC (<10%) and low sol-gel transition temperatures compared to BAB
      type copolymers. As the temperature increases further gel-sol transition is
      observed, which would result from the shrinkage of micelles with temperature
      increase. The hydrodynamic size of the micelles is monitored by dynamic laser
      scattering, and a possible gelation mechanism was suggested.

PMID- 12007200
TI  - Membrane-encased polymer millirods for sustained release of 5-fluorouracil.
AB  - This article describes the design and development of a novel membrane-encased
      polymer millirod for the sustained release of an anticancer drug, 5-fluorouracil
      (5-FU). The millirod consists of two functional compartments: (1) an inner 5-FU
      loaded monolithic millirod as the drug depot, and (2) an outer NaCl-impregnated
      polymer membrane to control the release rate of 5-FU. The inner millirod is
      fabricated by a compression-heat molding procedure to permit the entrapment of 5
      FU particles in the poly(D,L-lactide-co-glycolide) (PLGA) matrix. The drug
      loading density is controlled at 30 w/w% to achieve a burst release of 5-FU (>90%
      of the drug are released within 48 h) from the monolithic millirod. The NaCl
      impregnated PLGA membrane is generated by solvent casting and is then wrapped
      over the monolithic millirod to produce the membrane-encased millirod. Scanning
      electron microscopy shows that dissolution of NaCl particles produces a
      semipermeable polymer membrane to provide a sustained release of 5-FU. The
      membrane thickness and the density of NaCl particles inside the membrane are
      useful parameters to control the release kinetics of 5-FU. Under the experimental
      conditions in this study, sustained release of 5-FU [rates between 0.1 and 0.4
      mg/(day. cm of millirod)] is achieved for 2 to 5 weeks in phosphate-buffered
      saline (pH 7.4) at 37 degrees C. Results from this study demonstrate that
      membrane-encased polymer millirods provide controllable sustained release
      kinetics for applications in intratumoral drug delivery.

PMID- 12007199
TI  - Application of frog (Rana tigerina Daudin) skin collagen as a novel substrate in
      cell culture.
AB  - Collagen and collagen-based materials have extensive application in biomedical
      devices and tissue engineering. The current paper pertains to the application of
      frog (Rana tigerina Daudin) skin collagen as a novel substrate in cell culture.
      The study deals with the behavior, morphology, and physiology of keratinocytes
      and fibroblasts over dry and reconstituted collagen substratum, which are the key
      cells involved in wound repair. The advantage of using frog skin collagen as a
      substratum lies in the ease with which the reconstituted gel can be formed.
      Further, frog skin collagen is highly hydrophilic, which may be attributed to the
      fact that amphibians, as the first vertebrates connecting water and land, must
      have evolved certain physiologic specializations. These studies also contribute
      to the hypothesis that part of the healing efficacy of frog skin may be due to
      the collagen since proliferation, migration, and differentiation of epithelial
      cells are prime requisites for a normal healing mechanism.

PMID- 12007201
TI  - Interactions of 3T3 fibroblasts and endothelial cells with defined pore features.
AB  - The colonization of biodegradable polymer scaffolds with cell populations has
      been established as the foundation for the engineering of a number of tissues,
      including cartilage, liver, and bone. Within these scaffolds, the cells encounter
      a porous environment in which they must migrate across the convoluted polymer
      surface to generate a homogenous cell distribution. Predicting the interactions
      between cells and pores is important if scaffold characteristics are to be
      optimized. Therefore, we investigated the behavior of two model cell types over a
      range of defined pore features. These pore features range from 5 to 90 microm in
      diameter and have been fabricated by photolithographic techniques.
      Quantitatively, the behavior of the cells is dependent on three factors: 1)
      percentage cell coverage of the surface; 2) pore size; and 3) cell type.
      Fibroblast cells displayed a co-operative pattern of cell spreading in which
      pores with diameters greater than the cell dimensions were bridged by groups of
      cells using their neighbors as supports. Endothelial cells were unable to use
      neighbors as support structures and failed to bridge pores greater than the cell
      diameter.

PMID- 12007202
TI  - Micro-wear patterns on UHMWPE tibial inserts in total knee joint simulation.
AB  - The objective of this study was to examine both simulator and retrieved total
      knee replacement polyethylene inserts to confirm, using scanning electron
      microscopy, whether similar micro-wear patterns to those seen on retrieved
      inserts were reproduced on simulator specimens. The simulator specimens consisted
      of samples subjected to sliding and rolling movement (Experiment 1) and to
      sliding movement only (Experiment 2). Samples from Experiment 1 demonstrated
      longitudinal patterns in the middle of the wear track and transverse patterns in
      the anterior and posterior ends, whereas in Experiment 2, only transverse
      patterns were observed. In the retrieved specimens, both longitudinal and
      transverse patterns were observed. The results showed that the simulator study
      reproduced similar patterns of micro-damage on polyethylene, and that the
      longitudinal micro-wear pattern was related to the rolling movement that is
      distinctive in knee kinematics.

PMID- 12007203
TI  - Characterization of angiogenesis and inflammation surrounding ePTFE implanted on
      the epicardium.
AB  - The response of epicardial tissue to the implantation of expanded
      polytetrafluoroethylene (ePTFE) was evaluated and compared with identical
      material implanted within subcutaneous and adipose tissues. These two tissue
      environments were selected for comparison with epicardial implants because they
      represent tissue often involved in device implantation. Discs of ePTFE (6 mm)
      were implanted into three different tissue sites in Sprague-Dawley rats. At 5
      weeks, polymers and surrounding tissues were harvested and processed for light
      microscopy. General histology and histochemistry data indicated all polymers to
      be well incorporated with new tissue. Subcutaneous implants were covered by a
      dense fibrous capsule (55-70 microm). Epicardial and adipose implants had no
      fibrous capsule and a significantly greater number of microvessels (arterioles,
      capillaries, and venules) within the surrounding tissues compared with
      subcutaneous implants. An increased level of inflammation was also observed
      around epicardial implants compared with the other implants. Additionally, the
      new vasculature surrounding epicardially implanted ePTFE revealed an altered
      microvessel density and vessel type distribution compared with normal (control)
      epicardium. These results suggest that epicardial tissue responds to implanted
      ePTFE with a robust inflammatory response that may support the formation of a new
      microvasculature that is uniquely different from the native epicardial
      microvasculature.

PMID- 12007204
TI  - Nanoscale modifications of PET polymer surfaces via oxygen-plasma discharge yield
      minimal changes in attachment and growth of mammalian epithelial and mesenchymal
      cells in vitro.
AB  - Surface topography is believed to be a factor affecting cellular morphology,
      proliferation, and differentiation. The effect of surface roughness in the micron
      to supramicron range has been investigated previously. In the current study, the
      influence of nanoscale surface roughness was examined in terms of its effects on
      morphology, cytoskeleton expression, proliferation, differentiation, and
      apoptosis of three model cell types. Polyethylene terephthalate (PET) disks were
      etched using oxygen plasma to produce uniform and decidedly nanoscale levels of
      surface roughness. Three distinct types of cell lines-mouse 3T3-L1 preadipocytes,
      human JEG-3 choriocarcinoma cells, and human MCF-7 breast adenocarcinoma cells
      were cultured on the plasma-treated disks. Untreated PET disks were used as a
      control. Cytoskeletal proteins (F-actin and cytokeratin) exhibited similar
      patterns of expression. Cell morphology also was similar on both surfaces. Cell
      growth kinetics for the three types of cells and hormone secretion from the JEG-3
      cells were not significantly different from that of the controls (p > 0.05).
      However, the differentiation of preadipocyte 3T3-L1 cells into lipid-laden fat
      cells was modestly affected by nanoscale surface topography. In addition, 15
      deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2))-induced apoptosis of the JEG-3
      and MCF-7 cells revealed differences between the two surfaces. Plasma-treated
      surfaces showed more differentiated and apoptotic cells, respectively, compared
      to the controls. These results indicate that nanoscale roughness contributes in
      only moderate ways to cellular adhesion, proliferation, and differentiation in
      the cell lines tested.

PMID- 12007205
TI  - The use of liposomal enrofloxacin for intracellular infections in Kangal dogs and
      visualization of phagocytosis of liposomes.
AB  - It is difficult to treat intracellular infections because of the intrinsic
      resistance of the microorganism to most antibiotics. Moreover, these
      microorganisms can survive in phagocytic cells (macrophages and neutrophils). In
      this study, our aims were to encapsulate an antibiotic in liposomes, which will
      be phagocytized as well as the microorganisms in the phagocytic cell (because
      liposomes were prepared using lipids which have an antigenic activity and they
      can be phagocytized, thus, the active substance can be transferred into the
      cell), and to visualise with microscopy the phagocytic activity of macrophages
      and neutrophils to liposomes. MLV (multilamellar vesicles) fluorescein-labeled
      liposomes were prepared and incubated with isolated Kangal shepherd dog
      macrophages and neutrophils. The phagocytosis of liposomes by monocytes was
      visualized step by step under the microscope. Liposomes were also observed
      phagocytized after incubation with neutrophils. Enrofloxacin was chosen as a
      model drug. Neutrophils and macrophages were isolated from Kangal shepherd dogs
      and infected with Staphylococcus aureus, and their phagocytic activities (PA) and
      microbicidal activities (MA) were determined. PA and MA values were redetermined
      and compared when enrofloxacin formulations were used. Liposomal enrofloxacin was
      found to be more effective.

PMID- 12007206
TI  - Preparation of albumin preferential surfaces on poly(vinyl chloride) membranes
      via surface self-segregation.
AB  - Poly(vinyl chlorides)-graft-[omega-stearyl-poly(ethylene oxide)] (PVC-g-SPEO),
      which has a poly(vinyl chloride) (PVC) backbone, poly(ethylene oxide) (PEO) side
      chain, and stearyl end groups, has been synthesized. Self-organizing blends of
      the amphiphilic comb polymer in poly(vinyl chlorides) have been examined as a
      means to create albumin preferential surfaces on polymer films. X-ray
      photoelectron spectroscopy (XPS) analysis indicates substantial surface
      segregation of the PVC-g-SPEO. A surface concentration of 59.9 EO wt % is
      achieved by the solution casting and heat treatment of a film with a bulk
      concentration of only 3.78 EO wt %. In the aqueous environment, the surface
      rearrangement of PVC-g-SPEO/PVC blend film is limited and presents a high
      interfacial energy and high depolar component of interfacial energy due to the
      "tail-like" SPEO side chain. Protein adsorption tests confirm that PVC-g-SPEO/PVC
      blend films absorb high levels of albumin and dramatically resist fibrinogen
      adsorption. Surfaces to attract and reversibly bind albumin, which might diminish
      the occurrence of thrombosis, inflammation, and infection, are developed by self
      organizing blends of the amphiphilic comb polymer in poly(vinyl chlorides).

PMID- 12007207
TI  - Adsorption characteristics of human plasma fibronectin in relationship to cell
      adhesion.
AB  - Adsorption of human plasma fibronectin (FN) on nonsulfonated and sulfonated
      polymer surfaces was studied, by using a polyclonal antiserum to FN and the ELISA
      method. ELISA signal was recorded as a function of FN concentration in solutions.
      The concentration dependence of FN binding shows the saturation effect in the
      range 5-10 microg/mL. ELISA data are discussed in the terms of a self-assembled
      monolayer and different conformations of the FN molecule. The early adhesion of
      L1210 cells to polymer surfaces after prior adsorption of FN on these surfaces
      was studied under static conditions. In the case of FN adsorbed on sulfonated
      surfaces, the relative number of adhering cells increased with the increase of
      the interfacial surface tension (i.e., the cell adhesion depends on the surface
      density of sulfonic groups). However, in the case of FN adsorbed on nonsulfonated
      surfaces, the relative number of adhering cells was low and independent on the
      interfacial surface tension. The alpha(5)beta(1)-integrin blocking by a
      monoclonal antibody resulted in a strong inhibition of the cell adhesion to FN
      adsorbed on sulfonated polymer surfaces. This indicates that cell adhesion to FN
      adsorbed on these surfaces is mostly mediated by the alpha(5)beta(1)-integrin. In
      contrast, in the case of FN adsorbed on nonsulfonated surfaces the cell adhesion
      was not inhibited by the alpha(5)beta(1)-integrin blocking.

PMID- 12007208
TI  - Surface micromechanics of ultrahigh molecular weight polyethylene:
      Microindentation testing, crosslinking, and material behavior.
AB  - The wear behavior of ultrahigh molecular weight polyethylene (UHMWPE) is critical
      to the success of total joint replacements. Recent attempts to modify the wear
      behavior of UHMWPE by processing, in particular, crosslinking UHMWPE have shown
      promise to increase wear resistance, but concerns persist regarding other
      mechanical properties. It is also unclear what specific surface mechanical
      properties govern the wear resistance seen in these materials. The goal of this
      study was to demonstrate a custom-built surface mechanical test system and method
      that measures the micromechanical response of microtomed UHMWPE surfaces to depth
      sensing microindentation tests. The surface structure of these UHMWPE materials
      was also examined using scanning electron microscopy and atomic force microscopy.
      A custom designed microindentation test system assessed the microindentation
      behavior of three UHMWPE resins: 1. Hylamertrade mark, 2. GUR-1020 CMS, and 3.
      Marathontrade mark-a lightly crosslinked material. The effects of material and
      indentation depth were studied. Microindentation tests were performed with
      indentation depths ranging from 2 to 45 microm. Four different measurements of
      surface micromechanical behavior were obtained including the surface modulus,
      microhardness, hysteresis energy (irreversible work done to the sample per unit
      cycle) and its associated energy dissipation factor, and loading slope.
      Statistically significant differences in each of these parameters were found for
      each material. Generally, Hylamer had the largest values for these parameters,
      followed by the GUR resin and then the Marathon. Surface modulus was independent
      of depth of testing and found to be 651 MPa for Marathon, 738 MPa for GUR, and
      1015 MPa for Hylamer (Modulus for bulk UHMWPE is 540 MPa for Hylamer, 620 for
      GUR, and 1380 for Hylamer). The microhardness varied between 67 and 162 MPa
      depending on material and depth of testing. Surface structural characterization
      shows that the microtoming process for surface preparation generated distinct
      surface features that varied between materials. Intermittent drawn ribbons of
      polymer with oriented crystals were observed in both scanning electron microscopy
      and atomic force microscopy. The surface density and size of these features were
      characteristic of the materials with the Hylamer having the fewest, but largest
      ribbons, followed by GUR and then Marathon.

PMID- 12007209
TI  - Improvement in zirconia osseointegration by means of a biological glass coating:
      An in vitro and in vivo investigation.
AB  - The biocompatibility and osseointegration of zirconia (ZrO(2)), either coated
      with RKKP bioglazeor uncoated, were evaluated in vitro and in vivo. The in vitro
      test was performed in human osteoblasts, whereas maximal sensitization was
      performed in 23 Dunkin Hurtley guinea pigs. RKKP bioglaze-coated and uncoated
      (controls) ZrO(2) cylinders were implanted in the distal femoral epiphyses of 14
      Sprague-Dawley rats under general anesthesia, and animals were sacrificed at 30
      and 60 days. Lactate dehydrogenase, alkaline phosphatase, and Thiazolyl Blue
      (MTT) were tested in vitro. A graded score was used for evaluating the results of
      the sensitization test. Histomorphometry and microhardness testing were performed
      to quantify the osseointegration rate, as well as bone quality around the
      implants. Neither in vitro cytotoxicity nor sensitization were observed.
      Histomorphometry demonstrated that at 30 days, the affinity index was
      significantly higher in coated implants than in uncoated ones (p < 0.05); at 60
      days, the behavior of coated implants was better than that of uncoated ones, but
      differences were not significant. Significant increases in bone microhardness
      were found at 1000 microm from the interface area for both uncoated (p < 0.0005)
      and RKKP bioglaze-coated (p < 0.0005) ZrO(2), and also within 200 microm from the
      interface (p = 0.014) but only for coated ZrO(2.) These results suggest that RKKP
      bioglaze-coated ZrO(2) permits biocompatible devices with improved
      osseointegration properties to be manufactured.

PMID- 12007210
TI  - Interaction of human skin fibroblasts with moderate wettable polyacrylonitrile-
      copolymer membranes.
AB  - The development of a bioartificial skin is a step toward the treatment of
      patients with deep burns or nonhealing skin ulcers. One possible approach is
      based on growing dermal cells on membranes to obtain appropriate living cellular
      stroma (sheets) to cover the wound. New membrane-forming copolymers were
      synthesized, based on acrylonitrile (AN) copolymerization with hydrophilic N
      vinylpyrrolidone (NVP) monomer, in different percentage ratios, such as 5, 20,
      and 30% w/w, and with two other relatively high polar comonomers--namely, sodium
      2-methyl-2-propene-1-sulfonic acid (NaMAS) and aminoethylmethacrylate (AeMA). All
      these copolymers were characterized for their bulk composition and number average
      molecular weight, and used to prepare ultrafiltration membranes. Water contact
      angles and water uptake were estimated to characterize the wettability and
      scanning force microscopy to visualize the morphology of the resulting polymer
      surface. Cytotoxicity was estimated according to the international standard
      regulations, and the materials were found to be nontoxic. The interaction of the
      membranes with human skin fibroblasts was investigated considering that these
      cells are among the first to colonize membranes upon implantation or with
      prolonged external contact. The overall cell morphology, formation of focal
      adhesion contacts, and cell proliferation were estimated to characterize the cell
      material interactions. It was found that the pure polyacrylonitrile homopolymer
      (PAN) membrane provides excellent conditions for seeding with fibroblasts,
      comparable only to a copolymer containing AeMA. In contrast, the presence of
      NaMAS with acidic ionic groups decreased both the attachment and proliferation of
      fibroblasts. Low content of NVP in the copolymer, up to about 5%, still enabled
      good attachment and spreading of cells, as well as subsequent proliferation of
      fibroblasts, but higher ratios of 20 and 30% resulted in a significant decrease
      of these cellular activities.

PMID- 12007211
TI  - In vitro dissolution of melt-derived 45S5 and sol-gel derived 58S bioactive
      glasses.
AB  - Effects of powder type, particle size (5-20 microm; 90-300 microm; 90-710
      microm), and type of dissolution medium on the dissolution behavior of bioactive
      glasses were investigated in vitro using melt-derived 45S5 and sol-gel derived
      58S bioactive glass powders. Dissolution studies were performed in simulated body
      fluid and in alpha-MEM based cell culture medium at 37 degrees C under dynamic
      conditions (1 Hz) for periods of 30 min, 1, 2, 4, 8, 17, and 22 h. The
      concentrations of elements dissolved from the glasses were evaluated using
      inductively coupled plasma analysis. The reacted powders were analyzed for
      bioactivity using Fourier transform infrared spectrometry to observe the
      formation of a calcium phosphate layer on the surface. The non-porous surfaces of
      melt-derived 45S5 glass powders exhibited lower dissolution rates and rate of
      surface layer formation than 58S gel-glass powders. The rates of dissolution for
      both types of powders were lower in culture medium, compared to simulated body
      fluid, and increased as the particle size decreased. Thus, particle size range,
      glass type, and powder volume fraction can be used as a means to control the
      release rate of active ions that stimulate the gene expression and cellular
      response for tissue proliferation and repair.

PMID- 12007212
TI  - Accelerated aging studies of UHMWPE. I. Effect of resin, processing, and
      radiation environment on resistance to mechanical degradation.
AB  - The resin and processing route have been identified as potential variables
      influencing the mechanical behavior, and hence the clinical performance, of ultra
      high molecular weight polyethylene (UHMWPE) orthopedic components. Researchers
      have reported that components fabricated from 1900 resin may oxidize to a lesser
      extent than components fabricated from GUR resin during shelf aging after gamma
      sterilization in air. Conflicting reports on the oxidation resistance for 1900
      raise the question of whether resin or manufacturing method, or an interaction
      between resin and manufacturing method, influences the mechanical behavior of
      UHMWPE. We conducted a series of accelerated aging studies (no aging, aging in
      oxygen or in nitrogen) to systematically examine the influence of resin (GUR or
      1900), manufacturing method (bulk compression molding or extrusion), and
      sterilization method (none, in air, or in nitrogen) on the mechanical behavior of
      UHMWPE. The small punch testing technique was used to evaluate the mechanical
      behavior of the materials, and Fourier transform infrared spectroscopy was used
      to characterize the oxidation in selected samples. Our study showed that the
      sterilization environment, aging condition, and specimen location (surface or
      subsurface) significantly affected the mechanical behavior of UHMWPE. Each of the
      three polyethylenes evaluated seem to degrade according to a similar pathway
      after artificial aging in oxygen and gamma irradiation in air. The initial
      ability of the materials to exhibit post-yield strain hardening was significantly
      compromised by degradation. In general, there were only minor differences in the
      aging behavior of molded and extruded GUR 1050, whereas the molded 1900 material
      seemed to degrade slightly faster than either of the 1050 materials.

PMID- 12007213
TI  - Accelerated aging studies of UHMWPE. II. Virgin UHMWPE is not immune to oxidative
      degradation.
AB  - In Part I of this series, we showed that aging at elevated oxygen pressure is
      more successful at increasing the depth to which degradation occurs although it,
      too, generally causes greater degradation at the surface than at the subsurface.
      Therefore we hypothesized that thermal degradation alone, in the absence of free
      radicals, could be sufficient to artificially age UHMWPE in a manner analogous to
      natural aging. In the present study, virgin and air-irradiated UHMWPE (extruded
      GUR 1050 and compression-molded 1900) were aged up to 4 weeks at elevated oxygen
      pressure, and the mechanical behavior at the surface and subsurface was examined.
      All the materials were substantially degraded following 4 weeks of aging, but the
      spatial variations in the nonirradiated materials more closely mimicked the
      previously observed subsurface peak of degradation seen in naturally aged UHMWPE
      following irradiation in air. This aged material could provide a more realistic
      model for subsurface mechanical degradation, making it suitable for further
      mechanical testing in venues such as wear simulation.

PMID- 12007214
TI  - An improved method to prepare hyaluronic acid and type II collagen composite
      matrices.
AB  - An improved method to prepare hyaluronic acid (HyA) and type II collagen
      composite matrices was developed. HyA and type II collagen formed polyion complex
      (PIC) in aqueous solution due to their opposite electrostatic charges. Therefore,
      optimal conditions at which PIC was not formed between HyA and type II collagen
      were determined in order to directly crosslink using a water-soluble carbodiimide
      [WSC; 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride]. HyA
      collagen composite matrices were successfully obtained using WSC in the presence
      of 0.4M NaCl, which was found the optimal concentration to suppress PIC
      formation. Fourier transformed infrared spectra of the obtained matrices showed
      ester bond formation, indicating that the crosslinking reaction between HyA
      molecules, HyA and collagen molecules, and collagen molecules proceeded. The
      swelling ratio of a HyA-collagen composite matrix depended on the WSC
      concentration and HyA content. From scanning electron microscopy observations,
      the lyophilized matrices possess multi pore structures. The HyA-collagen
      composite matrices using this improved method will be useful in the preparation
      of cartilage regenerative scaffolds, and this methodology may be applied to other
      polyanion-polycation combinations as well.

PMID- 12007215
TI  - Performance of a polyurethane vascular prosthesis carrying a dipyridamole
      (Persantin) coating on its lumenal surface.

PMID- 12007216
TI  - Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with
      incidence data and application to screening.
AB  - Although there have been numerous reports from around the world of mutations in
      the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance
      regulator), little attention has been given to integrating these mutant alleles
      into a global understanding of the population molecular genetics associated with
      cystic fibrosis (CF). We determined the distribution of CFTR mutations in as many
      regions throughout the world as possible in an effort designed to: 1) increase
      our understanding of ancestry-genotype relationships, 2) compare mutational
      arrays with disease incidence, and 3) gain insight for decisions regarding
      screening program enhancement through CFTR multi-mutational analyses. Information
      on all mutations that have been published since the identification and cloning of
      the CFTR gene's most common allele, DeltaF508 (or F508del), was reviewed and
      integrated into a centralized database. The data were then sorted and regional
      CFTR arrays were determined using mutations that appeared in a given region with
      a frequency of 0.5% or greater. Final analyses were based on 72,431 CF
      chromosomes, using data compiled from over 100 original papers, and over 80
      regions from around the world, including all nations where CF has been studied
      using analytical molecular genetics. Initial results confirmed wide mutational
      heterogeneity throughout the world; however, characterization of the most common
      mutations across most populations was possible. We also examined CF incidence,
      DeltaF508 frequency, and regional mutational heterogeneity in a subset of
      populations. Data for these analyses were filtered for reliability and
      methodological strength before being incorporated into the final analysis.
      Statistical assessment of these variables revealed that there is a significant
      positive correlation between DeltaF508 frequency and the CF incidence levels of
      regional populations. Regional analyses were also performed to search for trends
      in the distribution of CFTR mutations across migrant and related populations;
      this led to clarification of ancestry-genotype patterns that can be used to
      design CFTR multi-mutation panels for CF screening programs. From comprehensive
      assessment of these data, we offer recommendations that multiple CFTR alleles
      should eventually be included to increase the sensitivity of newborn screening
      programs employing two-tier testing with trypsinogen and DNA analysis.

PMID- 12007217
TI  - The IARC TP53 database: new online mutation analysis and recommendations to
      users.
AB  - Mutations in the tumor suppressor gene TP53 are frequent in most human cancers.
      Comparison of the mutation patterns in different cancers may reveal clues on the
      natural history of the disease. Over the past 10 years, several databases of TP53
      mutations have been developed. The most extensive of these databases is
      maintained and developed at the International Agency for Research on Cancer. The
      database compiles all mutations (somatic and inherited), as well as
      polymorphisms, that have been reported in the published literature since 1989.
      The IARC TP53 mutation dataset is the largest dataset available on the variations
      of any human gene. The database is available at www.iarc.fr/P53/. In this paper,
      we describe recent developments of the database. These developments include
      restructuring of the database, which is now patient-centered, with more detailed
      annotations on the patient (carcinogen exposure, virus infection, genetic
      background). In addition, a new on-line application to retrieve somatic mutation
      data and analyze mutation patterns is now available. We also discuss limitations
      on the use of the database and provide recommendations to users.

PMID- 12007218
TI  - Arab genetic disease database (AGDDB): a population-specific clinical and
      mutation database.
AB  - Here we present the Arab Genetic Disease Database (AGDDB), a curated catalog of
      genetic disorders found in Arab populations. The first release of the database is
      populated primarily with information from the textbook Genetic Disorders Among
      Arab Populations [Teebi and Farag, 1997]. AGDDB is composed of data elements
      revolving around disorder reports. Other reports cover clinical, genomic,
      reference, and population frequency elements and their important attributes. The
      Arab Genetic Disease Consortium (30 investigators, 18 countries) is responsible
      for editing and reviewing AGDDB data. After initial indexing, AGDDB contains over
      1,000 unique disorder entries. Entries are linked to their counterparts in the
      Online Mendelian Inheritance in Man (OMIM) database; similar associations with
      relevant locus-specific and central mutation databases are planned. The database
      can be queried by keyword across all its fields, with more focused searches
      allowed. The database is freely available and may be accessed at www.agddb.org.
      The database serves as a robust prototype for cataloging variation and disorder
      information within a specific population.

PMID- 12007219
TI  - Mutation analysis in PKD1 of Japanese autosomal dominant polycystic kidney
      disease patients.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal
      disorder (incidence, 1:1,000). The mutation of PKD1 is thought to account for 85%
      of ADPKD. Although a considerable number of studies on PKD1 mutation have been
      published recently, most of them concern Caucasian ADPKD patients. In the present
      study, we examined PKD1 mutations in Japanese ADPKD patients. Long-range
      polymerase chain reaction (LR-PCR) with PKD1-specific primers followed by nested
      PCR was used to analyze the duplicated region of PKD1. Six novel chain
      terminating mutations were detected: three nonsense mutations (Q2014X transition
      in exon 15, Q2969X in exon 24, and E2810X in exon 23), two deletions (2132del29
      in exon10 and 7024delAC in exon 15), and one splicing mutation (IVS21-2delAG).
      There was also one nonconservative missense mutation (T2083I). Two other
      potentially pathogenic missense mutations (G2814R and L2816P) were on the
      downstream site of one nonsense mutation. These three mutations and a following
      polymorphism (8662C>T) were probably the result of gene conversion from one of
      the homologous genes to PKD1. Six other polymorphisms were found. Most PKD1
      mutations in Japanese ADPKD patients were novel and definitely pathogenic. One
      pedigree did not link to either PKD1 or PKD2.

PMID- 12007220
TI  - Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes
      expressed in Escherichia coli.
AB  - Deficiency of propionyl-CoA carboxylase (PCC) results in propionic acidemia, an
      autosomal recessive disorder characterized by ketoacidosis sufficiently severe to
      cause neonatal death. PCC is involved in the catabolism of branched-chain amino
      acids, odd-chain fatty acids, and cholesterol. The enzyme is a biotin-dependent
      mitochondrial protein composed of two heterologous subunits arranged into an 800
      kDa alpha(6 )beta(6) dodecameric structure. Approximately 60 mutations have been
      reported in the nuclear genes PCCA and PCCB that encode the two PCC subunits. The
      vast majority of these mutations have not been examined at the protein level. We
      present an initial characterization of 13 mutations located in exons 1, 3-7, and
      12-14 of PCCB. After expression in E. coli, these recombinant mutant enzymes were
      analyzed for stability, biotinylation, alpha-beta subunit interaction, and
      activity. Our results show a functional dichotomy in these PCCB mutations with
      some mutants (R44P, S106R, G131R, G198D, V205D, I408del, and M442T) capable of
      varying degrees of assembly but forming catalytically inactive PCC proteins.
      Other PCCB mutants (R165W, E168K, D178H, P228L, and R410W) that are PCC deficient
      in patient-derived fibroblasts, were found to be capable of expressing wild-type
      level PCC activity when assembled in our chaperone-assisted E. coli expression
      system. This result indicates that these mutations exert their pathogenic effect
      due to an inability to assemble correctly in patients' cells. This initial screen
      has identified a range of mutant PCC proteins that are sufficiently stable to be
      purified and subsequently used for structure-function analysis to further
      elucidate the complex relationship between genotype and phenotype in propionic
      acidemia.

PMID- 12007221
TI  - High homocysteine and thrombosis without connective tissue disorders are
      associated with a novel class of cystathionine beta-synthase (CBS) mutations.
AB  - Cystathionine beta-synthase (CBS) is a crucial regulator of plasma levels of the
      thrombogenic amino acid homocysteine (Hcy). Homocystinuria due to CBS deficiency
      confers a dramatically increased risk of thrombosis. Early diagnosis usually
      occurs after the observation of ectopia lentis, mental retardation, or
      characteristic skeletal abnormalities. Homocystinurics with this phenotype
      typically carry mutations in the catalytic region of the protein that abolish CBS
      activity. We describe a novel class of missense mutations consisting of I435T,
      P422L, and S466L that are located in the non-catalytic C-terminal region of CBS
      that yield enzymes that are catalytically active but deficient in their response
      to S-adenosylmethionine (AdoMet). The P422L and S466L mutations were found in
      patients suffering premature thrombosis and homocystinuric levels of Hcy but
      lacking any of the connective tissue disorders typical of homocystinuria due to
      CBS deficiency. The P422L and S466L mutants demonstrated a level of CBS activity
      comparable to that of the AdoMet stimulated wild-type CBS but could not be
      further induced by the addition of AdoMet. In terms of temperature stability,
      oligomeric organization, and heme saturation the I435T, P422L, and S466L mutants
      are indistinguishable from wild-type CBS. Our findings illustrate the importance
      of AdoMet for the regulation of Hcy metabolism and are consistent with the
      possibility that the characteristic connective tissue disturbances observed in
      homocystinuria due to CBS deficiency may not be due to elevated Hcy.

PMID- 12007222
TI  - Restriction endonuclease fingerprinting enhanced conformation sensitive gel
      electrophoresis (REF-CSGE) in the analysis of BRCA1 exon 11 mutations in a high
      risk breast cancer cohort.
AB  - Efficient genetic analysis of large exonic regions containing heterozygous
      mutations and common polymorphisms can be difficult. We have analyzed 30 patients
      for inherited susceptibility mutations (ISM) within exon 11 of the BRCA1 gene as
      part of an ongoing genetic epidemiological study of high-risk breast cancer
      (HRBC). A novel combination of restriction endonuclease fingerprinting (REF) and
      conformation sensitive gel electrophoresis (CSGE) was developed for rapid and
      efficient screening of mutations. This method (REF-CSGE) was compared side-by
      side with standard CSGE and evaluated for both efficiency and sensitivity of
      detection. REF-CSGE detected 100% of the alterations found by CSGE. However, one
      variant was only detectable by REF-CSGE. All samples with variant bands were
      sequenced to confirm the nature of the alteration. In total, two small deletions
      (frameshifts) and 62 point mutations (60 known polymorphisms and two variants of
      unknown significance) were found in our cohort. The majority of the exon 11
      polymorphisms detected are inherited as a linked haplotype. Point mutations that
      comprise these haplotypes could be simultaneously detected on a single gel by REF
      CSGE, thereby decreasing the number of sequencing reactions necessary to
      elucidate heteroduplex patterns seen on CSGE gels. An analysis of the overall
      efficiency of both techniques revealed that REF-CSGE required 67% fewer
      confirmatory sequencing reactions, resulting in savings in both reagents and
      technician time.

PMID- 12007267
TI  - 'Unruffling' the mystique of therapeutic touch. And voices against TT.

PMID- 12007223
TI  - Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.
AB  - Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC
      gene. This study included 71 Israeli families referred for molecular analysis of
      the APC gene. Analysis was performed by the protein truncation test (PTT) of exon
      15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found
      in 36 (50.7%) probands. Mutation detection rates depended on the pattern of
      referral, such that among the 40 probands referred from the Service for
      Hereditary Cancer the mutation detection rate was 70%, whereas among the 31
      probands referred by other gastroenterologists detection rate was significantly
      lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within
      exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14.
      A relatively high proportion of the mutations was detected in exon 9 (6/36), five
      of them newly described. Altogether, we describe here 17 new mutations. Within
      the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi
      origin, there was no significant differences in the mutation detection rate or
      the distribution of mutations within the APC gene. No founder mutation was
      detected in any of these populations. Our data confirm that higher detection
      rates may be expected in patients referred by clinical services specializing in
      hereditary colon cancer. These results further underscore the importance of
      complete analysis of all exons and exon/intron boundaries, in order to achieve
      maximal detection rate in patients suspected of FAP.

PMID- 12007268
TI  - Localisation of the subthalamic nucleus using Radionics Image Fusion and
      Stereoplan combined with field potential recording. A technical note.
AB  - Subthalamic nucleus stimulation is an effective therapy for alleviating
      parkinsonian tremor, rigidity and bradykinesia. Although microelectrode recording
      is said to be essential for accurate targeting, this often prolongs the operation
      and the multiple recording tracts required may increase the incidence of
      complications, particularly haemorrhage. We describe a technique for implantation
      of deep brain electrodes in the subthalamic nucleus using MRI/CT fusion for
      anatomical localisation followed by bipolar recording of focal field potentials
      via the implanted stimulating electrode for neurophysiological confirmation of
      the stimulation site. The technique is effective, safe and requires much less
      time, and can be used as an alternative method to microelectrode recording.

PMID- 12007269
TI  - Delayed onset of the supplementary motor area syndrome after surgical resection
      of the mesial frontal lobe: a time course study using intraoperative mapping in
      an awake patient.
AB  - Although the occurrence of the supplementary motor area (SMA) syndrome has been
      extensively reported following mesial lobe surgery, to our knowledge the time
      course of disease onset was never accurately documented. We describe a patient
      without deficit, despite harboring a glioma invading the left SMA. This patient
      was operated under local anesthesia, to perform intraoperative online
      sensorimotor and language mapping using electrical stimulations throughout the
      resection. No deficit was noted at the end of the tumor and SMA removal. The
      patient was maintained awake to perform an immediate control MRI. Aphasia and
      right hemiplegia occurred 30 min after the SMA resection. Total recovery was
      observed within 2 months. This work shows that the SMA syndrome may not occur
      immediately after SMA resection. We suggest that the transient compensation of
      the SMA function is likely due to residual activity of an oscillatory loop and/or
      short-term plasticity (rapid unmasking of parallel networks), with final recovery
      occurring due to long-term plasticity (neosynaptogenesis).

PMID- 12007270
TI  - Functional recovery after combined cerebral and cerebellar hemispherectomy in the
      rat.
AB  - The cerebellum seems to be one of the structures responsible for early
      neurological improvement after cerebral hemispherectomy and its consequent
      deficits. Considered as an accessory brain, the cerebellum may constitute a
      neurobiological substrate for the recovery of such extensive cortical and
      subcortical lesions. It may compensate for the injury by structural remodeling
      and plasticity. The authors observed that, indeed, rats submitted to
      contralateral hemicerebellectomy before cerebral hemispherectomy do not recover
      as well as those submitted to hemicerebellectomy 2 weeks after cerebral
      hemispherectomy.

PMID- 12007271
TI  - Is distortion correction necessary for digital subtraction angiography in the
      Gamma Knife treatment of intra-cranial arteriovenous malformations?
AB  - OBJECTIVE: The published literature maintains that distortion correction of
      digital subtraction angiography is essential for accurate definition of the
      arteriovenous malformation (AVM) nidus when performing Gamma Knife radiosurgery.
      However, as Gamma Knife treatments usually involve small volume targets, which
      are purposely positioned as close to the centre of the frame as possible, we
      postulated that the angiographic target images should be minimally distorted.
      Thus, the use of uncorrected images would not significantly compromise the
      accuracy of the treatment. We investigated this postulate. DESIGN: Patient and
      phantom images with and without distortion correction were assessed. The errors
      measured in the angiograms were compared to those of MR and CT images of the same
      subjects. Any errors less than 0.5 mm in any modality were accepted as intrinsic.
      RESULTS: All errors measured in the study were sub-millimetre. In the patient
      group, errors with distortion correction averaged 0.13 mm (range 0-0.3 mm).
      Without distortion correction, errors averaged 0.34 mm (range 0.1-0.6 mm). By
      comparison, the average error for intracranial MR imaging was 0.3 mm, with a
      maximum of 0.6 mm. CONCLUSION: For small, intracranial AVMs distortion correction
      did not significantly reduce the errors associated with the definition of the
      stereotactic co-ordinates. We suggest that prior to the purchase of this
      software, similar in-house testing should be performed.

PMID- 12007272
TI  - Risk management in a community Gamma Knife unit.
AB  - OBJECTIVE: The records of the San Diego Gamma Knife Center were retrospectively
      reviewed for unprogrammed events as part of a risk management assessment.
      MATERIALS AND METHODS: Review was made of the physicist notes of the first 1,000
      patients successfully treated at the center. This encompassed 1,020 stereotactic
      frame placement procedures, accompanied by Gamma Knife radiosurgery in 98.0% of
      intended cases. A total of 7,145 Gamma Knife shots were delivered to 1,509
      lesions. RESULTS: Of the 43 unprogrammed events documented, 8 were patient
      related and 14 were related to lesion growth or location; these were considered
      unavoidable. Further, one event was related to dose administration, 5 to
      diagnosis, 15 to technique; these were considered potentially avoidable. This
      yielded an avoidable error rate of 2.1% per patient, 1.4% per lesion treated, and
      0.29% per shot. It was clear that more avoidable errors occurred early in the
      center's operation, consistent with a learning curve. Review of individual
      physician's cases revealed none appeared more likely to have an avoidable event.
      CONCLUSIONS: Consistently high quality may be achieved at a community-based Gamma
      Knife center if sufficient multidisciplinary involvement is achieved.

PMID- 12007274
TI  - Magnitude of microelectrode refinement in pallidotomy and thalamotomy.
AB  - The relative accuracy of starting point algorithms in microelectrode-guided
      stereotactic pallidotomy and thalamotomy was evaluated using postoperative
      magnetic resonance imaging (MRI) data. Multiplanar reformations were performed to
      align postoperative MRI in anterior-posterior, dorsal-ventral and mediolateral
      planes. Three-dimensional distance and direction from the pallidal and thalamic
      stereotactic starting points to the respective radiofrequency lesions were
      measured. Similar magnitude of microelectrode refinement in pallidotomy and
      thalamotomy suggested similar accuracy of algorithms used to set the stereotactic
      starting point. Fewer microelectrode-recording tracts were required to identify
      optimal lesioning sites in thalamotomy compared to pallidotomy. Lesions were
      consistently localized anterior and superior to the starting point and a refined
      starting point algorithm may reduce the number of microelectrode recording
      tracts.

PMID- 12007275
TI  - Tactile discrimination task not disturbed by thalamic stimulation.
AB  - The major pathway of human somatosensation passes through the ventrocaudal
      nucleus (Vc) of the thalamus. We tested the effect of direct electrical
      stimulation of the Vc on tactile discrimination in 5 Parkinson patients
      undergoing stereotactic thalamotomy. Raised gratings with lines 3, 4, or 6 mm
      apart were used. Patients had to actively touch test patterns placed in the hand
      contralateral to the thalamus under operation and compare it with a reference 3
      mm grating held continuously in their other hand. Their performance was best for
      6-mm, followed by 3-mm and then by 4-mm patterns regardless of electrical
      stimulation. Under Vc stimulation, patients recognized the 4-mm gratings slightly
      better. This can be explained either by the nature of thalamocortical
      interaction, which makes it resistant to external noise, or by the involvement of
      other pathways that circumvent the effect of thalamic stimulation.

PMID- 12007276
TI  - Stereotactic radiosurgery for primary trigeminal neuralgia using the Leksell
      Gamma unit.
AB  - OBJECTIVE: Previous papers have reported Gamma Knife radiosurgery to be a safe,
      effective method for primary trigeminal neuralgia. Since November 1996, we have
      treated primary trigeminal neuralgia using the Leksell Gamma Knife at the Tianjin
      Medical University. The present study reports clinical results of Gamma Knife
      radiosurgery in the treatment of trigeminal neuralgia in 80 cases. METHODS: The
      mean patient age was 67 years (range 32-92), the mean duration of facial pain was
      7.6 years (range 1.5-29). The male:female ratio was 31:49. The right side of the
      face was involved in 45 patients (56.25%) and the left side in 30 cases (37.5%),
      with bilateral involvement in 5 cases (6.25%). Under local anesthesia, all
      patients underwent stereotactic MRI to identify the trigeminal nerve. A single
      isocenter, using a 4-mm collimator, was positioned at the sensory root of the
      trigeminal nerve entry zone of the pons, 4-6 mm from the brainstem surface, so
      that no more than the 20% isodose was administered to the brainstem. The maximum
      dose was between 70 and 90 Gy, with a mean of 75.6 Gy. For bilateral trigeminal
      neuralgia, two separate matrices were employed, and bilateral Gamma Knife
      radiosurgery was performed on the same day. RESULTS: Follow-up ranged from 12 to
      43 months (mean 23.7 months). Neurological evaluation indicated excellent
      response in 42 cases (52.5%), good response in 25 cases (31.25%), effective
      response in 8 cases (10%), so the total pain control rate was 93.75%. The latency
      from Gamma Knife surgery to pain relief ranged from 1 to 120 days (mean 22 days).
      Among the 75 patients 7 with pain control experienced pain recurrence 5-26 months
      after being completely free from pain. A second Gamma Knife radiosurgery was
      performed in 7 recurrent cases and 5 patients with treatment failure. A maximal
      dose ranging from 70 to 80 Gy was given (mean 74.2 Gy). After a mean follow-up of
      18 months (8-33 months), 9 patients achieved excellent results, and 2 had good
      results. The latency interval to pain relief ranged from 1 to 120 days (mean 15
      days). Nine patients developed new facial numbness, while no other complication
      appeared in the remainder of the patients. CONCLUSIONS: Gamma Knife radiosurgery
      is a safe and effective method in the treatment of trigeminal neuralgia once
      diagnosis is established.

PMID- 12007277
TI  - Factors influencing early complications following Gamma Knife radiosurgery. A
      prospective study.
AB  - PURPOSE: The factors influencing early complications following Gamma Knife
      radiosurgery have not been definitely established. We report a prospective study
      evaluating the incidence of early complications (occurring within 3 months of
      radiosurgery) and various factors associated with early complications following
      stereotactic Gamma Knife radiosurgery for intracranial lesions. PATIENTS AND
      METHODS: Seventy-nine previously unirradiated consecutive adult patients (82
      lesions: arteriovenous malformations 35, benign tumors 43, metastases 4) treated
      by Gamma Knife radiosurgery were studied between May 1997 and August 1998. The
      median target volume was 4.8 cm(3). The median dose of 15 Gy was prescribed to
      the 50% isodose. Patients were evaluated clinically and radiologically (with
      CT/MRI/SPECT) at 3-month intervals for the 1st year and 6 monthly thereafter.
      Complications were further divided as immediate (occurring within 24 h) or acute
      (occurring from 1 day to 3 months). RESULTS: Early complications were observed in
      19/79 (24.0%) patients. These included immediate in 10 (12.7%) and acute
      complications in 9 (11.3%) patients and were characterized by headache,
      nausea/vomiting, vertigo and seizures. No severe early complications were
      observed. Radiological changes in the form of perilesional edema were seen in
      8/82 (9.8%) lesions. Maximum target diameter >25 mm was the only factor
      significantly associated with early complications by univariate analysis (p =
      0.0335). Multivariate analysis revealed maximum target diameter >25 mm and
      prescribed dose >20 Gy to be significantly associated with early complications (p
      = 0.0442 and p = 0.0083, respectively). CONCLUSION: Up to one fourth of the
      patients undergoing Gamma Knife radiosurgery for intracranial lesions can
      experience self-limiting early toxicity. The selection of targets with small
      diameter and volume may reduce the risk of early complications following Gamma
      Knife radiosurgery.

PMID- 12007278
TI  - Miniature multileaf collimator as an alternative to traditional circular
      collimators for stereotactic radiosurgery and stereotactic radiotherapy.
AB  - PURPOSE: To evaluate the miniature multileaf collimator (MMLC) as an alternative
      to traditional circular collimators for radiosurgery. MATERIALS AND METHODS:
      'Circular' fields were created with the Radionics MMLC (leaf width 3.53 mm at
      isocenter). Beam data, including tissue maximum ratios, output factors, penumbrae
      and isodose distributions of these fields were measured. These were compared to
      the Radionics circular collimators traditionally used for radiosurgery. The MMLC
      data were input to the XKnife Treatment Planning System. Treatment plans were
      completed and evaluated using both the MMLC 'circular' fields and the circular
      collimators. RESULTS: MMLC fields using 3, 5, 7, 9, 11, and 13 leaves on each
      side of the Radionics MMLC were created to approximate circular fields. The TMRs
      are essentially identical to those of comparable-size circular collimators.
      Measured at isocenter at 5-cm depth for 6 MV, the 80-20% penumbra widths are
      comparable to circular collimators, but are increased by as much as 1 mm at the
      leaf intersections (steps) where scalloping occurs. Isodose distributions were
      matched to those of circular collimators with comparable 50% isodose widths.
      Treatment plans for the MMLC 'circular' fields with four arcs (totaling 360
      degrees) are essentially identical to those of comparable circular collimators.
      Dose-volume histograms revealed clinically insignificant differences between the
      two in doses to the target, to the volume surrounding the target, and to adjacent
      critical normal tissues. There is very little discrepancy between the dose
      distribution calculated with the approximated MMLC fields and with those of
      simulated arcs with the actual MMLC fields. CONCLUSIONS: With the MMLC simulating
      circular fields, dose distributions may be obtained which are essentially
      identical to comparable-size circular collimators. The mechanical accuracy of the
      MMLC is as good as that of the circular collimators, and the leakage dose is
      less. The diameter of 'circular' fields is limited by the MMLC leaf width to 1 cm
      and greater in increments of 7 mm. Attention needs to be paid to mechanical
      collisions because the MMLC is bulkier than the circular collimators.

PMID- 12007279
TI  - Macrophage biology and pathobiology in the evolution of immune responses: a
      functional analysis.
AB  - A number of general principles of macrophage biology and pathobiology are
      formulated to define the contribution of macrophages to the kinetics and
      sequencing of innate and adaptive immune responses more precisely. The
      application of these principles to modelling immune responses and to macrophage
      based treatments of immune disorders is discussed. The concept of innate
      peripheral tolerance is developed. It is suggested that macrophage activation
      could be a primary determinant of nearly every aspect of immune responsiveness,
      both normal and abnormal, as might be predicted from the innate immune response
      to 'danger' being evolutionarily more primitive than the adaptive.

PMID- 12007280
TI  - Pre-eclampsia-associated differential expression of proteoglycans in the
      umbilical cord arteries.
AB  - OBJECTIVE: The role of proteoglycans (PGs) of the umbilical cord arteries (UCAs)
      in the pathomechanism of pre-eclampsia is not known. Therefore we decided to
      compare the PGs of normal (control) UCAs and those of newborns delivered by
      mothers with pre-eclampsia. METHODS: PGs were extracted in dissociative
      conditions, purified by Q-Sepharose anion exchange chromatography and
      lyophilized. They were analyzed by gel filtration and SDS-PAGE before and after
      treatment with chondroitinase ABC. RESULTS: It was found that the PG preparation
      from pre-eclamptic UCAs had a higher amount of sulphated glycosaminoglycans (in
      relation to protein) than in the case of control UCAs. The predominant PG
      fraction included small PGs with core proteins of 45 and 47 kD, immunologically
      related to biglycan (45 kD) and decorin (45 and 47 kD). The expression of decorin
      core proteins was increased and that of biglycan slightly decreased in pre
      eclamptic UCAs. Some other putative small PG core proteins (56, 53, 49, 42, 38
      and 34 kD) were also found. They were present in higher amounts in pre-eclamptic
      UCAs. Larger PGs (core proteins of 99-110 and >150 kD), were detected in lower
      amounts, both in control and particularly in pre-eclamptic material. CONCLUSION:
      Pre-eclampsia is associated with alterations in PG composition of the UCAs. They
      may affect the mechanical properties of this organ and disturb fetal blood
      circulation.

PMID- 12007281
TI  - Expression of MRE11 complex (MRE11, RAD50, NBS1) and hRap1 and its relation with
      telomere regulation, telomerase activity in human gastric carcinomas.
AB  - The MRE11 complex (MRE11, RAD50, NBS1) are required for the repair of DNA double
      strand breaks and have another important function in regulating telomere length.
      The silent information regulator (Sir) proteins required for telomere position
      effect also bind telomeres. hRap1 protein is a human ortholog of yeast Rap1 which
      regulates telomere length by interacting with TRF2 and is recruited to telomeres
      by TRF2. We examined the expression of the MRE11 complex (MRE11, RAD50, NBS1),
      Sir2 and hRAP1 in 20 gastric carcinomas by reverse transcription polymerase chain
      reaction and then analyzed the relation between telomerase activity and other
      telomerase components such as human telomerase reverse transcriptase (TERT),
      human telomerase RNA component (hTR), human telomerase-associated protein (TEP1),
      telomeric repeat binding factor 1 (TRF1), TRF2- and TRF1-interacting, ankyrin
      related ADP-ribose polymerase (tankyrase) as well as TRF1-interacting nuclear
      protein 2 (TIN2). Of twenty gastric carcinomas examined, 13 (65%), 14 (70%), 16
      (80%), 12 (60%) and 13 (65%) expressed MRE11, RAD50, NBS1, Sir2 and hRap1 at
      higher levels than corresponding nonneoplastic gastric mucosa, respectively. No
      obvious correlation was observed between MRE11 complex expression and telomerase
      activity or expression of TERT, hTR, TEP1, tankyrase and TIN2. Carcinomas with
      high TRF1 expression expressed significantly higher levels of MRE11 and RAD50
      than those with low TRF1 expression (p < 0.05). On the other hand, carcinomas
      with high TRF2 expression expressed significantly higher levels of MRE11, NBS1
      and hRap1 than those with low TRF2 expression (p < 0.05). These results suggest
      that gastric carcinomas with high TRF1 and TRF2 expression may need a large
      quantity of the MRE11 complex. Moreover, gastric carcinomas with high TRF1
      expression may require a large quantity of hRap1.

PMID- 12007282
TI  - Imaging of aortic atherosclerotic lesions by (125)I-LDL, (125)I-oxidized-LDL,
      (125)I-HDL and (125)I-BSA.
AB  - OBJECTIVE: The aim of the present study was to compare the accumulation of (125)I
      labeled low-density lipoproteins (LDL), oxidized LDL (oxLDL), HDL and BSA in
      advanced atherosclerotic lesions of apoE-deficient mice. METHODS: (125)I
      lipoproteins or (125)I-BSA were injected into the tail vein of apoE-deficient
      mice. Blood clearance of (125)I-lipoproteins and (125)I-BSA and their
      accumulation in atherosclerotic lesions were assayed. RESULTS: Blood clearance of
      (125)I-LDL and (125)I-HDL was moderate, and approximately 30% of the injected
      lipoproteins were present in plasma 24 h following injection. oxLDL was removed
      much faster from plasma, and less than 10% of (125)I-oxLDL was present in the
      circulation 30 min after (125)I-oxLDL injection. The clearance of (125)I-BSA from
      the circulation was slower than the lipoprotein clearance. The highest
      accumulation of LDL, oxLDL, HDL and BSA was detected in atherosclerotic lesions
      in the aortic arch and abdominal aorta, while lower accumulation was detected in
      the less atherosclerotic descending thoracic aorta. CONCLUSION: Our findings
      demonstrate that both (125)I-HDL and (125)I-BSA as well as (125)I-LDL are
      accumulated in atherosclerotic plaques and that they can be used for the
      detection of atherosclerotic lesions.

PMID- 12007283
TI  - Effect of IL-2 and IL-6 on parameters related to metastatic activity in a murine
      melanoma.
AB  - Previous results have shown that the metastatic colonization with B16F10 melanoma
      in vivo increased after in vitro treatment of the cells with IL-2 or IL-6. To
      further investigate the mechanisms underlying this effect, we have studied
      adhesion, invasion, and proliferation properties of B16 melanoma, using two
      sublines with different metastatic ability. Adhesion of tumor cells to Matrigel
      coats increased using IL-6, which also induced upregulation of VLA-4 expression
      in both sublines. Unexpectedly, invasion through Matrigel filters was almost
      completely inhibited by IL-6 and decreased in the presence of IL-2. Cell growth
      was not affected by these interleukins; however, IL-6 could partially overcome
      the proliferation blockade induced by stress conditions. Taken together, these
      results suggest that upregulation of adhesion properties and/or the protective
      effect induced by IL-6 could account for the enhancement of metastasis exerted by
      this interleukin.

PMID- 12007284
TI  - "Pinopodes" and implantation.

PMID- 12007285
TI  - Mucins and blastocyst attachment.

PMID- 12007286
TI  - Paracrine interactions during human implantation.

PMID- 12007287
TI  - Integrins and implantation in the human.

PMID- 12007288
TI  - Control of uterine receptivity and embryo implantation by steroid hormone
      regulation of LIF production and LIF receptor activity: towards a molecular
      understanding of "the window of implantation".

PMID- 12007289
TI  - Transcriptional regulation of implantation by HOX genes.

PMID- 12007290
TI  - Proteases at the endometrial-trophoblast interface: their role in implantation.

PMID- 12007291
TI  - Nitric oxide and its role in blastocyst implantation.

PMID- 12007292
TI  - Preeclampsia, an implantation disorder.

PMID- 12007293
TI  - Chemokine expression and function at the human maternal-fetal interface.

PMID- 12007398
TI  - Computational genomics of noncoding RNA genes.
AB  - The number of known noncoding RNA genes is expanding rapidly. Computational
      analysis of genome sequences, which has been revolutionary for protein gene
      analysis, should also be able to address questions of the number and diversity of
      noncoding RNA genes. However, noncoding RNAs present computational genomics with
      a new set of challenges.

PMID- 12007399
TI  - Small RNAs in bacteria: diverse regulators of gene expression in response to
      environmental changes.
AB  - Bacterial small, untranslated RNAs are important regulators that often act to
      transmit environmental signals when cells encounter suboptimal or stressful
      growth conditions. These RNAs help modulate changes in cellular metabolism to
      optimize utilization of available nutrients and improve the probability for
      survival.

PMID- 12007400
TI  - Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular
      functions.
AB  - Small nucleolar RNAs represent an abundant, evolutionarily ancient group of
      noncoding RNAs which possess impressively diverse functions ranging from 2'-O
      methylation and pseudouridylation of various classes of RNAs, through nucleolytic
      processing of rRNAs to the synthesis of telomeric DNA.

PMID- 12007401
TI  - Spliceosomal snRNAs: Mg(2+)-dependent chemistry at the catalytic core?
AB  - Since the discovery of self-splicing RNAs, it has been suspected that the snRNAs
      are the catalytic components of the spliceosome. Recent evidence supports both
      the catalytic potential of the spliceosomal snRNAs and their resemblance to
      elements of group II introns.

PMID- 12007402
TI  - Structure and function of the eukaryotic ribosome: the next frontier.
AB  - As the catalytic and regulatory centers of protein synthesis in cells, ribosomes
      are central to many aspects of cell and structural biology. Recent work
      highlights the unique properties and complexity of eukaryotic ribosomes and their
      component rRNAs and proteins.

PMID- 12007403
TI  - PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of
      the JAK-STAT signaling pathway in a process requiring PKD2.
AB  - Autosomal dominant polycystic kidney disease is characterized by cyst formation
      in the kidney and other organs and results from mutations of PKD1 or PKD2.
      Previous studies suggest that their gene products have an important role in
      growth regulation. We now show that expression of polycystin-1 activates the JAK
      STAT pathway, thereby upregulating p21(waf1) and inducing cell cycle arrest in
      G0/G1. This process requires polycystin-2, a channel protein, as an essential
      cofactor. Mutations that disrupt polycystin-1/2 binding prevent activation of the
      pathway. Mouse embryos lacking Pkd1 have defective STAT1 phosphorylation and
      p21(waf1) induction. These results suggest that one function of the polycystin
      1/2 complex is to regulate the JAK/STAT pathway and explain how mutations of
      either gene can result in dysregulated growth.

PMID- 12007404
TI  - An induced Ets repressor complex regulates growth arrest during terminal
      macrophage differentiation.
AB  - Defining the molecular mechanisms that coordinately regulate proliferation and
      differentiation is a central issue in development. Here, we describe a mechanism
      in which induction of the Ets repressor METS/PE1 links terminal differentiation
      to cell cycle arrest. Using macrophages as a model, we provide evidence that
      METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent
      expression of cell type-specific genes by selectively replacing Ets activators on
      the promoters of cell cycle control genes. Antiproliferative effects of METS
      require its interaction with DP103, a DEAD box-containing protein that assembles
      a novel corepressor complex. Functional interactions between the METS/DP103
      complex and E2F/ pRB family proteins are also necessary for inhibition of
      cellular proliferation, suggesting a combinatorial code that directs permanent
      cell cycle exit during terminal differentiation.

PMID- 12007405
TI  - BES1 accumulates in the nucleus in response to brassinosteroids to regulate gene
      expression and promote stem elongation.
AB  - Plant steroid hormones, known as brassinosteroids (BRs), signal through a plasma
      membrane localized receptor kinase BRI1. We identified bes1, a semidominant
      suppressor of bri1, which exhibits constitutive BR response phenotypes including
      long and bending petioles, curly leaves, accelerated senescence, and constitutive
      expression of BR-response genes. BES1 accumulates in the nucleus in response to
      BRs. BES1 is phosphorylated and appears to be destabilized by the glycogen
      synthase kinase-3 (GSK-3) BIN2, a negative regulator of the BR pathway. These
      results establish a signaling cascade for BRs with similarities to the Wnt
      pathway, in which signaling through cell surface receptors leads to inactivation
      of a GSK-3 allowing accumulation of a nuclear protein that regulates target gene
      expression.

PMID- 12007406
TI  - The transcriptional regulator RfaH stimulates RNA chain synthesis after
      recruitment to elongation complexes by the exposed nontemplate DNA strand.
AB  - The transcriptional regulatory protein RfaH controls expression of several
      operons that encode extracytoplasmic components in bacteria. Regulation by RfaH
      occurs during transcript elongation and depends on a 5'-proximal, transcribed
      nucleic acid sequence called ops that induces transcriptional pausing in vitro
      and in vivo. We report that RfaH recognizes RNA polymerase transcribing RfaH
      regulated operons by interacting with the ops sequence in the exposed nontemplate
      DNA strand of ops-paused transcription complexes. Although RfaH delays escape
      from the ops pause, once escape occurs, RfaH enhances elongation by suppressing
      pausing and rho-dependent termination without apparent involvement of other
      accessory proteins. This activity predicts a cumulative antitermination model for
      RfaH's regulation of ops-containing operons in vivo.

PMID- 12007407
TI  - Regulation of motor neuron pool sorting by differential expression of type II
      cadherins.
AB  - During spinal cord development, motor neurons with common targets and afferent
      inputs cluster into discrete nuclei, termed motor pools. Motor pools can be
      delineated by transcription factor expression, but cell surface proteins that
      distinguish motor pools in a systematic manner have not been identified. We show
      that the developmentally regulated expression of type II cadherins defines
      specific motor pools. Expression of one type II cadherin, MN-cadherin, regulates
      the segregation of motor pools that are normally distinguished by expression of
      this protein. Type II cadherins are also expressed by proprioceptive sensory
      neurons, raising the possibility that cadherins regulate additional steps in the
      development of sensory-motor circuits.

PMID- 12007408
TI  - Anosmin-1, defective in the X-linked form of Kallmann syndrome, promotes axonal
      branch formation from olfactory bulb output neurons.
AB  - The physiological role of anosmin-1, defective in the X chromosome-linked form of
      Kallmann syndrome, is not yet known. Here, we show that anti-anosmin-1 antibodies
      block the formation of the collateral branches of rat olfactory bulb output
      neurons (mitral and tufted cells) in organotypic cultures. Moreover, anosmin-1
      greatly enhances axonal branching of these dissociated neurons in culture. In
      addition, coculture experiments with either piriform cortex or anosmin-1
      producing CHO cells demonstrate that anosmin-1 is a chemoattractant for the axons
      of these neurons, suggesting that this protein, which is expressed in the
      piriform cortex, attracts their collateral branches in vivo. We conclude that
      anosmin-1 has a dual branch-promoting and guidance activity, which plays an
      essential role in the patterning of mitral and tufted cell axon collaterals to
      the olfactory cortex.

PMID- 12007409
TI  - Spatial representation of the glomerular map in the Drosophila protocerebrum.
AB  - In the fruit fly, Drosophila, olfactory sensory neurons expressing a given
      receptor project to spatially invariant loci in the antennal lobe to create a
      topographic map of receptor activation. We have asked how the map in the antennal
      lobe is represented in higher sensory centers in the brain. Random labeling of
      individual projection neurons using the FLP-out technique reveals that projection
      neurons that innervate the same glomerulus exhibit strikingly similar axonal
      topography, whereas neurons from different glomeruli display very different
      patterns of projection in the protocerebrum. These results demonstrate that a
      topographic map of olfactory information is retained in higher brain centers, but
      the character of the map differs from that of the antennal lobe, affording an
      opportunity for integration of olfactory sensory input.

PMID- 12007410
TI  - Representation of the glomerular olfactory map in the Drosophila brain.
AB  - We explored how the odor map in the Drosophila antennal lobe is represented in
      higher olfactory centers, the mushroom body and lateral horn. Systematic single
      cell tracing of projection neurons (PNs) that send dendrites to specific
      glomeruli in the antennal lobe revealed their stereotypical axon branching
      patterns and terminal fields in the lateral horn. PNs with similar axon terminal
      fields tend to receive input from neighboring glomeruli. The glomerular classes
      of individual PNs could be accurately predicted based solely on their axon
      projection patterns. The sum of these patterns defines an "axon map" in higher
      olfactory centers reflecting which olfactory receptors provide input. This map is
      characterized by spatial convergence and divergence of PN axons, allowing
      integration of olfactory information.

PMID- 12007411
TI  - Asymmetric cell division in B. subtilis involves a spiral-like intermediate of
      the cytokinetic protein FtsZ.
AB  - A fundamental feature of development in the spore-forming bacterium Bacillus
      subtilis is the switch from medial to asymmetric division. The switch is brought
      about by a change in the location of the cytokinetic Z ring, which is composed of
      the tubulin-like protein FtsZ, from the cell middle to the poles during
      sporulation. We report that the medial Z ring is replaced by a spiral-like
      filament of FtsZ that grows along the long axis of the cell. We propose that the
      filament mediates the switch by redeploying FtsZ to the poles. Spiral formation
      and the switch to polar Z rings are largely caused by a sporulation-specific
      increase in transcription of the gene for FtsZ and activation of the gene for the
      FtsZ-associated protein SpoIIE.

PMID- 12007412
TI  - Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4
      kinase-dependent and -independent components.
AB  - BACKGROUND: Phosphoinositides are required for the recruitment of many proteins
      to both the plasma membrane and the endosome; however, their role in protein
      targeting to other organelles is less clear. The pleckstrin homology (PH) domains
      of oxysterol binding protein (OSBP) and its relatives have been shown to bind to
      the Golgi apparatus in yeast and mammalian cells. Previous in vitro binding
      studies identified phosphatidylinositol (PtdIns) (4)P and PtdIns(4,5)P(2) as
      candidate ligands, but it is not known which is recognized in vivo and whether
      phosphoinositide specificity can account for Golgi-specific targeting. RESULTS:
      We have examined the distribution of GFP fusions to the PH domain of OSBP and to
      related PH domains in yeast strains carrying mutations in individual
      phosphoinositide kinases. We find that Golgi targeting requires the activity of
      the PtdIns 4-kinase Pik1p but not phosphorylation of PtdIns at the 3 or 5
      positions and that a PH domain specific for PtdIns(4,5)P(2) is targeted
      exclusively to the plasma membrane. However, a mutant version of the OSBP PH
      domain that does not bind phosphoinositides in vitro still shows some targeting
      in vivo. This targeting is independent of Pik1p but dependent on the Golgi GTPase
      Arf1p. CONCLUSIONS: Phosphorylation of PtdIns at the 4 position but not
      conversion to PtdIns(4,5)P(2) contributes to recruitment of PH domains to the
      Golgi apparatus. However, potential phosphoinositide ligands for these PH domains
      are not restricted to the Golgi, and the OSBP PH domain also recognizes a second
      determinant that is ARF dependent, indicating that organelle specificity reflects
      a combinatorial interaction.

PMID- 12007413
TI  - Arp2/3-dependent pseudocleavage [correction of psuedocleavage] furrow assembly in
      syncytial Drosophila embryos.
AB  - BACKGROUND: In syncytial blastoderm Drosophila embryos, actin caps assemble
      during telophase. As the cell cycle progresses through interphase, these small
      caps expand and fuse to form pseudocleavage furrows that are structurally related
      to the cleavage furrows that assemble during somatic cell division. The molecular
      mechanism driving cell cycle coordinated actin reorganization from the caps to
      the furrows is not understood. RESULTS: We show that Drosophila embryos contain a
      typical Arp2/3 complex and that components of this complex localize to the
      margins of the expanding caps, to mature pseudocleavage furrows, and to somatic
      cell cleavage furrows during the postcellularization embryonic divisions. A
      mutation that disrupts the arpc1 subunit of Arp2/3 leads to spindle fusions that
      are characteristic of pseudocleavage furrow disruption. By contrast, this
      mutation does not significantly affect nuclear positioning during interphase,
      which is dependent on actin cap function. In vivo analysis of actin
      reorganization demonstrates that the arpc1 mutation does not prevent assembly of
      small actin caps but blocks cap expansion and furrow assembly as the cell cycle
      progresses through interphase. The scrambled gene is also required for cap
      expansion and furrow assembly, and Scrambled is required for Arp2/3 localization
      to the cap margins. CONCLUSIONS: The Drosophila Arp2/3 complex and Scrambled
      protein are required for actin cap expansion and pseudocleavage furrow formation
      during the syncytial blastoderm divisions. We propose that Scrambled-dependent
      localization of Arp2/3 to the margins of the expanding caps triggers local actin
      polymerization that drives cap expansion and pseudocleavage furrow assembly.

PMID- 12007414
TI  - Genome-wide transcript profiles in aging and calorically restricted Drosophila
      melanogaster.
AB  - BACKGROUND: We characterized RNA transcript levels for the whole Drosophila
      genome during normal aging. We compared age-dependent profiles from animals aged
      under full-nutrient conditions with profiles obtained from animals maintained on
      a low-calorie medium to determine if caloric restriction slows the aging process.
      Specific biological functions impacted by caloric restriction were identified
      using the Gene Ontology annotation. We used the global patterns of expression
      profiles to test if particular genomic regions contribute differentially to
      changes in transcript profiles with age and if global disregulation of gene
      expression occurs during aging. RESULTS: Whole-genome transcript profiles
      contained a statistically powerful genetic signature of normal aging. Nearly 23%
      of the genome changed in transcript representation with age. Caloric restriction
      was accompanied by a slowing of the progression of normal, age-related changes in
      transcript levels. Many genes, including those associated with stress response
      and oogenesis, showed age-dependent transcript representation. Caloric
      restriction resulted in the downregulation of genes primarily involved in cell
      growth, metabolism, and reproduction. We found no evidence that age-dependent
      changes in transcription level were confined to genes localized to specific
      regions of the genome and found no support for widespread disregulation of gene
      expression with age. CONCLUSIONS: Aging is characterized by highly dynamic
      changes in the expression of many genes, which provides a powerful molecular
      description of the normal aging process. Caloric restriction extends life span by
      slowing down the rate of normal aging. Transcription levels of genes from a wide
      variety of biological functions and processes are impacted by age and dietary
      conditions.

PMID- 12007415
TI  - Importance of a myosin II-containing progenitor for actomyosin ring assembly in
      fission yeast.
AB  - An actomyosin-based contractile ring provides the forces necessary for cell
      cleavage in several organisms [1-3]. Myosin II is an essential component of the
      actomyosin ring and has also been detected as a "spot" in interphase
      Schizosaccharomyces pombe cells [4-5]. It is currently unknown if this myosin II
      containing spot is important for cytokinesis. In this study, we characterize this
      myosin II-containing spot using a combination of genetic and cell biological
      analyses. Whereas myosin II at the actomyosin ring undergoes rapid turnover,
      myosin II at the spot does not. Maintenance of the myosin II-containing spot is
      independent of F-actin function. Interestingly, maintenance of this myosin II
      spot in interphase requires the function of Rng3p, a UCS domain-containing
      protein, the Caenorhabditis elegans homolog of which has recently been shown to
      be a cochaperone for myosin II assembly [6]. Disassembly of the spot in
      interphase prevents actomyosin ring formation in the subsequent mitosis, implying
      that the spot might represent a progenitor that is important for assembly of the
      actomyosin ring. Given that mitosis represents a short period of the fission
      yeast cell cycle, organization of this progenitor structure in interphase might
      ensure proper assembly of the actomyosin ring and successful cell division.

PMID- 12007416
TI  - C. elegans responds to chemical repellents by integrating sensory inputs from the
      head and the tail.
AB  - The phasmids are bilateral sensory organs located in the tail of Caenorhabditis
      elegans and other nematodes. The similar structures of the phasmids and the
      amphid chemosensory organs in the head have long suggested a chemosensory
      function for the phasmids. However, the PHA and PHB phasmid neurons are not
      required for chemotaxis or for dauer formation, and no direct proof of a
      chemosensory function of the phasmids has been obtained. C. elegans avoids toxic
      chemicals by reversing its movement, and this behavior is mediated by sensory
      neurons of the amphid, particularly, the ASH neurons. Here we show that the PHA
      and PHB phasmid neurons function as chemosensory cells that negatively modulate
      reversals to repellents. The antagonistic activity of head and tail sensory
      neurons is integrated to generate appropriate escape behaviors: detection of a
      repellent by head neurons mediates reversals, which are suppressed by
      antagonistic inputs from tail neurons. Our results suggest that C. elegans senses
      repellents by defining a head-to-tail spatial map of the chemical environment.

PMID- 12007417
TI  - Identification of tissue-specific microRNAs from mouse.
AB  - MicroRNAs (miRNAs) are a new class of noncoding RNAs, which are encoded as short
      inverted repeats in the genomes of invertebrates and vertebrates. It is believed
      that miRNAs are modulators of target mRNA translation and stability, although
      most target mRNAs remain to be identified. Here we describe the identification of
      34 novel miRNAs by tissue-specific cloning of approximately 21-nucleotide RNAs
      from mouse. Almost all identified miRNAs are conserved in the human genome and
      are also frequently found in nonmammalian vertebrate genomes, such as pufferfish.
      In heart, liver, or brain, it is found that a single, tissue-specifically
      expressed miRNA dominates the population of expressed miRNAs and suggests a role
      for these miRNAs in tissue specification or cell lineage decisions. Finally, a
      miRNA was identified that appears to be the fruitfly and mammalian ortholog of C.
      elegans lin-4 stRNA.

PMID- 12007418
TI  - Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus.
AB  - The Wiskott-Aldrich syndrome protein family member N-WASP is a key integrator of
      the multiple signalling pathways that regulate actin polymerization via the
      Arp2/3 complex. Our previous studies have shown that N-WASP is required for the
      actin-based motility of vaccinia virus and is recruited via Nck and WIP. We now
      show that Grb2 is an additional component of the vaccinia actin tail-forming
      complex. Recruitment of Nck and Grb2 to viral particles requires phosphorylation
      of tyrosine residues 112 and 132 of A36R, the vaccinia actin tail nucleator,
      respectively. The presence of Grb2 on the virus is also dependent on the
      polyproline-rich region of N-WASP. The Grb2 pathway alone is therefore unable to
      nucleate actin tails, as its recruitment requires the prior recruitment of N-WASP
      by Nck. However, Grb2 does play an important role in actin-based motility of
      vaccinia, as in its absence, the mean number of actin tails per cell is reduced
      2.6-fold. Thus, both Nck and Grb2 act in a cooperative manner to stabilize and/or
      activate the vaccinia actin-nucleating complex. We suggest that such
      cooperativity between "primary" and "secondary" adaptor proteins is likely to be
      a general feature of receptor-mediated signalling.

PMID- 12007419
TI  - Ca(2+) oscillations promote APC/C-dependent cyclin B1 degradation during
      metaphase arrest and completion of meiosis in fertilizing mouse eggs.
AB  - Cyclin B1, the regulatory component of M phase-promoting factor (MPF), is
      degraded during the metaphase-anaphase transition in an anaphase-promoting
      complex/cyclosome (APC/C)-dependent process. MPF activity is stable in eggs, and
      a sperm-triggered Ca(2+) signal is needed to promote cyclin degradation. In
      frogs, a single Ca(2+) spike promotes cell cycle resumption, but, in mammals, the
      Ca(2+) signal is more complex, consisting of a series of spikes that stop several
      hours after sperm fusion. Using dual imaging in mouse eggs, we have examined how
      the Ca(2+) signal generates cyclin B1 destruction using destructible and
      nondestructible GFP-tagged constructs. APC/C activity was present in unfertilized
      eggs, giving cyclin B1 a half-life of 1.15 +/- 0.28 hr. However, APC/C-dependent
      cyclin degradation was elevated 6-fold when sperm raised cytosolic Ca(2+) levels
      above 600 nM. This activation was transitory since cyclin B1 levels recovered
      between Ca(2+) spikes. For continued cyclin degradation at basal Ca(2+) levels,
      multiple spikes were needed. APC/C-mediated degradation was observed until eggs
      had completed meiosis with the formation of pronuclei, and, at this time, Ca(2+)
      spikes stopped. Therefore, the physiological need for a repetitive Ca(2+) signal
      in mammals is to ensure long-term cyclin destruction during a protracted exit
      from meiosis.

PMID- 12007420
TI  - Tea3p is a cell end marker activating polarized growth in Schizosaccharomyces
      pombe.
AB  - Eukaryotic cells are often polarized in their cytoplasmic structures, and this
      can be important for their function. The fission yeast Schizosaccharomyces pombe
      is a highly polarized cell that extends bipolarly along a single axis to generate
      a rod-shaped cell. It divides by medial fission to generate two equal-sized
      daughter cells that resume growth only at the old end. Once these cells have
      reached a particular length, they undergo NETO, new end take-off, whereby growth
      is activated at the other end to generate bipolarly extending cells. The
      activation and positioning of these growth zones are essential for maintaining
      growth in a straight line. Genetic analyses have identified many proteins
      involved in this process, like the cell end markers Tea1p and Pom1p and the
      kinases Orb2p/Shk1p/Pak1, Ssp1p, and Wee1p. Here, we describe tea3, a gene
      encoding a tea1-like protein with some similarities to ERM proteins. Tea3p is
      required for efficient NETO and for the proper placement of the septum. Like
      Pom1p, Tea3p localizes to cell ends, and its localization depends on microtubules
      and Tea1p. We propose that Tea3p is a novel cell end marker required specifically
      to activate polarized cell growth at the second end during NETO.

PMID- 12007421
TI  - Critical role for CCA1 and LHY in maintaining circadian rhythmicity in
      Arabidopsis.
AB  - Circadian clocks are autoregulatory, endogenous mechanisms that allow organisms,
      from bacteria to humans, to advantageously time a wide range of activities within
      24-hr environmental cycles. CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE
      ELONGATED HYPOCOTYL (LHY) are thought to be important components of the circadian
      clock in the model plant Arabidopsis. The similar circadian phenotypes of lines
      overexpressing either CCA1 or LHY have suggested that the functions of these two
      transcription factors are largely overlapping. cca1-1 plants, which lack CCA1
      protein, show a short-period phenotype for the expression of several genes when
      assayed under constant light conditions. This suggests that LHY function is able
      to only partially compensate for the lack of CCA1 protein, resulting in a clock
      with a faster pace in cca1-1 plants. We have obtained plants lacking CCA1 and
      with LHY function strongly reduced, cca1-1 lhy-R, and show that these plants are
      unable to maintain sustained oscillations in both constant light and constant
      darkness. However, these plants exhibit some circadian function in light/dark
      cycles, showing that the Arabidopsis circadian clock is not entirely dependent on
      CCA1 and LHY activities.

PMID- 12007422
TI  - The MYST domain acetyltransferase Chameau functions in epigenetic mechanisms of
      transcriptional repression.
AB  - Reversible acetylation of histone tails plays an important role in chromatin
      remodelling and regulation of gene activity. While modification by histone
      acetyltransferase (HAT) is usually linked to transcriptional activation, we
      provide here evidence for HAT function in several types of epigenetic repression.
      Chameau (Chm), a new Drosophila member of the MYST HAT family, dominantly
      suppresses position effect variegation (PEV), is required for the maintenance of
      Hox gene silencing by Polycomb group (PcG) proteins, and can partially substitute
      for the MYST Sas2 HAT in yeast telomeric position effect (TPE). Finally, we
      provide in vivo evidence that the acetyltransferase activity of Chm is required
      in these processes, since a variant protein mutated in the catalytic domain no
      longer rescues PEV modification, telomeric silencing of SAS2-deficient yeast
      cells, nor lethality of chm mutant flies. These findings emphasize the role of an
      acetyltransferase in gene silencing, which supports, according to the histone
      code hypothesis, that transcription at a particular locus is determined by a
      precise combination of histone tail modifications rather than by overall
      acetylation levels.

PMID- 12007423
TI  - Trunk neural crest has skeletogenic potential.
AB  - During early vertebrate development, neural crest cells emerge from the dorsal
      neural tube, migrate into the periphery, and form a wide range of derivatives.
      There is, however, a significant difference between the cranial and trunk neural
      crest with respect to the diversity of cell types that each normally produces.
      Thus, while crest cells from all axial levels form neurons, glia, and
      melanocytes, the cranial crest additionally generates skeletal derivatives such
      as bone and cartilage; trunk crest cells are generally thought to lack
      skeletogenic potential. Here, we show, however, that if avian trunk neural crest
      cells are cultured in appropriate media, they form both bone and cartilage cells,
      and if placed into the developing head, they contribute to cranial skeletal
      components. Thus, the neural crest from all axial levels can generate the full
      repertoire of crest derivatives. The skeletogenic potential of the trunk neural
      crest is significant, as it was likely realized in early vertebrates, which had
      extensive postcranial exoskeletal coverings.

PMID- 12007424
TI  - Lateral transfer of an EF-1alpha gene: origin and evolution of the large subunit
      of ATP sulfurylase in eubacteria.
AB  - It is generally accepted that new genes arise via duplication and functional
      divergence of existing genes, in accordance with Ohno's model, now called
      "Mutation During Redundancy," or MDR. In this model, one of the two gene copies
      is free to acquire novel (although likely related) activities through mutation,
      since only one copy is required for its original function. However, duplication
      within a genome is not the only process that might give rise to this situation:
      acquisition of a functionally redundant gene by lateral gene transfer (LGT) could
      also initiate the MDR process. Here we describe a probable instance, involving
      LGT of an archaeal or eukaryotic elongation factor 1alpha (EF-1alpha) gene. The
      large subunit of ATP sulfurylase (CysN or the N-terminal portion of NodQ), found
      mainly in proteobacteria, is clearly related to translation elongation factors.
      However, our analyses show that cysN arose from an EF-1alpha gene initially
      acquired by LGT, not from a within-genome duplication of the resident EF-Tu gene.
      To our knowledge, this is the first unequivocal case of LGT followed by
      functional modification to be described; this mechanism could be a potentially
      important force in establishing genes with novel functions in genomes.

PMID- 12007425
TI  - Treatment fillip for gene therapy ambitions.

PMID- 12007426
TI  - When push comes to shove.

PMID- 12007427
TI  - Cesar Milstein (1927-2002).

PMID- 12007428
TI  - BDNF.

PMID- 12007429
TI  - Ageing: the many-headed monster.
AB  - Ageing involves numerous pathways that are not functionally coordinated. The
      genome-wide profiling of transcription during Drosophila ageing is proving to be
      a powerful new tool for identifying these pathways.

PMID- 12007430
TI  - Inositol phosphates: a remarkably versatile enzyme.
AB  - Ins(3,4,5,6)P(4) is an inhibitor of Ca(2+)-activated Cl(-) channels, but further
      understanding has been hindered by ignorance of how it is made in cells. It now
      transpires that one protein with ATP-dependent kinase and phosphatase activities
      interconverts Ins(3,4,5,6)P(4) and Ins(1,3,4,5,6)P(5), as well as several other
      inositol polyphosphates.

PMID- 12007431
TI  - Mitosis: aurora gives chromosomes a healthy stretch.
AB  - Attachment of sister chromatids to microtubules from opposite spindle poles--bi
      orientation--generates tension at the kinetochores. The Ipl1/Aurora B kinase
      responds to the absence of tension at mono-oriented chromosomes and promotes
      microtubule turnover and spindle checkpoint activation until a stable bi-oriented
      attachment is achieved.

PMID- 12007432
TI  - Gene expression: the close coupling of transcription and splicing.
AB  - Increasing evidence indicates that the transcriptional machinery can influence
      the efficiency of splicing as well as splice-site selection. Surprisingly, it has
      now been demonstrated that splicing components influence the efficiency of
      transcription. This mutual stimulation has important implications for the
      regulation of gene expression.

PMID- 12007433
TI  - Asthma: T-bet--a master controller?
AB  - The transcription factors T-bet and GATA3 are important reciprocal determinants
      of Th1 and Th2 T helper cell differentiation. Recent evidence suggests that these
      factors may affect airway immunopathology in asthma.

PMID- 12007434
TI  - MAP kinase module: the Ksr connection.
AB  - Ksr has been genetically defined as a component of the Ras/MAP kinase pathway,
      but its role has been unclear. New studies now provide evidence that Ksr is
      important for signal transmission within the MAP kinase module, where it
      apparently acts as a location-regulated scaffold connecting MEK to Raf.

PMID- 12007435
TI  - Population genomics: ageing by association.
AB  - Mutations in the gene Klotho lead to premature ageing in mice. Recent work on
      human genetic variation has identified an association between a particular allele
      of Klotho and human lifespan. A harbinger of things to come, this work
      illustrates the power and growth potential for association studies of human
      ageing.

PMID- 12007436
TI  - Cell cycle: stressed out of mitosis.
AB  - Cells in early stages of chromosome condensation are very vulnerable, and many
      stresses that do not damage DNA induce a transient return to late G2 phase. Such
      stresses include the drug-induced disassembly of microtubules, which triggers an
      ATM-independent G2 checkpoint pathway involving a novel ubiquitin ligase.

PMID- 12007437
TI  - Cytokinesis: myosin spots the ring.
AB  - Faithful actomyosin ring assembly is pivotal for successful cell division. The
      mechanisms by which the actomyosin ring is assembled at the correct time and
      place remain unclear. Recent studies in fission yeast have shown that a myosin II
      containing spot may be a novel progenitor structure essential for actomyosin ring
      assembly.

PMID- 12007438
TI  - Evaluation of the clinical utility of a rapid blood test for human leptospirosis.
AB  - A rapid assay device for the detection of Leptospira-specific immunoglobulin M
      (IgM) antibodies was applied on whole blood samples collected from a group of
      consecutive patients admitted with clinical suspicion of leptospirosis to a
      district hospital in Kerala, India. The hospital is located in an area that is
      endemic for leptospirosis. The results of the rapid assay showed an agreement of
      94.3% with those of an IgM ELISA routinely used for the serodiagnosis of
      leptospirosis. The rapid assay was simply performed by the addition of 10 microL
      blood to the sample well of a plastic assay device followed by the addition of
      130 microL sample fluid. The assay was read after 10 min by visual inspection and
      was scored positive when staining of the antigen line in the test zone was
      observed. The assay utilizes stabilised components and can be stored without the
      need for refrigeration. These characteristics make the assay ideal in areas where
      the disease is common and where laboratory support is not routinely available.

PMID- 12007439
TI  - Rapid type-specific diagnosis of adenovirus type 4 infection using a hexon-based
      quantitative fluorogenic PCR.
AB  - A hexon-based fluorogenic polymerase chain reaction (PCR) assay utilizing the 5'
      nuclease activity of DNA Taqpolymerase was developed as a rapid and type-specific
      diagnostic system for adenovirus type 4 (Ad4) detection and quantification. The
      assay consists of a pair of flanking primers and an internal fluorescence labeled
      probe that allows real time amplification to quantify the Ad4 virus. One out of
      12 flanking primer pairs evaluated (combinations of three forward primers and
      four reverse primers) was found to be optimal for Ad4 virus detection that
      yielded background-free operation, i.e., no fluorescent signal generated by non
      template controls. The assay was employed to detect Ad4 reference virus strain RI
      67, Wyeth Ad4 vaccine strain and 71 different clinical Ad4 isolates from US
      military recruits used in this study with consistent sensitivity (lower detection
      limit) of 2-4 pfu per PCR reaction. The assay showed linear Ad4 detection with a
      dynamic range of greater than five logs (from 2-4 pfu/assay to greater than 10(5)
      pfu/assay). This Ad4-specific assay did not crossreact with representative
      members of Ad subgroups A, B, C, D and F at viral concentrations greater than
      10(8) pfu/ml. It was also demonstrated that Ad4 viruses could be efficiently
      detected from throat swabs (71/72 specimens or 98.6% detection sensitivity) of
      infected patients by the Ad4-specific PCR. In general, there was a good
      correlation between PCR determined viral titers in throat swabs and time required
      to detect viral cytopathic effects (CPE) in cell culture. Evaluation of the
      simple Ad4 specific assay developed in this study could be used to provide a
      rapid clinically relevant diagnosis of Ad4 infections in patients with acute
      respiratory disease (ARD).

PMID- 12007440
TI  - Detergent extract from chlamydial elementary bodies used as antigen for enzyme
      linked immunosorbent assay.
AB  - Soluble antigen (SA) from chlamydial elementary bodies (EBs) was extracted with N
      lauroylsarcosine. The extracted SA composed of lipopolysaccharide (LPS) and
      proteins was compared with EBs using an enzyme-linked immunosorbent assay
      (ELISA). Patient sera from natural chlamydial infections exhibited ELISA mean
      absorbance (A(492) and A(405/650)) values 2-5 times higher with SA than with EBs,
      resulting in a better discrimination between positive and negative human sera.

PMID- 12007441
TI  - PCR tools for the differential diagnosis of Taenia saginata and Taenia solium
      taeniasis/cysticercosis from different geographical locations.
AB  - The potential value of PCRs in the species-specific diagnosis of have been
      investigated, using samples of T. saginata and T. solium from different
      geographical areas. The PCRs examining inter-species differences were based on
      the sequence of the HDP2 DNA fragment, specific for T. saginata/T. solium, and
      the sequence of the rDNA internal transcribed spacer 1 and spacer 2 (ITS-1 and
      ITS-2). This PCR analysis of DNA isolates confirmed morphologic diagnosis and
      allowed the speciation of samples too small or fragmented for morphologic
      identification, with clear and consistent inter-species differences between T.
      saginata (twenty-two) and T. solium (three) geographical isolates. Possible intra
      species genomic variability, within these species, was similarly studied through
      analysis of PCR amplification products (PCR-RFLP) and only encountered one
      exceptional T. saginata isolate from Kenya, which yielded a unique PCR-RFLP
      pattern, different from T. saginata DNA of Mexican (one sample) and Spanish
      (seven samples) origin.

PMID- 12007442
TI  - The use of direct agglutination test (DAT) in serological diagnosis of Ethiopian
      cutaneous leishmaniasis.
AB  - Leishmania aethiopica (L.a.) is the main species of Leishmania that causes
      Ethiopian cutaneous leishmaniasis (ECL). The routine diagnosis of ECL depends on
      parasitological examination of smear, culture or biopsy. In this study, DAT was
      set-up and evaluated for its diagnostic performance using defined sera of 45 ECL
      patients, 18 visceral leishmaniasis (VL) patients, 12 patients with other
      diseases, and 37 normal controls. The test was also evaluated in 64 patients
      clinically diagnosed as ECL, leprosy, or other skin diseases. Using L.a. derived
      antigen, the sensitivity and specificity of the test was determined to be 90.5%
      and 91.8% respectively. However, using antigen derived from a non-homologous
      strain, only 4 sera of 21 active ECL patients were positive. Eighteen sera of VL
      patients were positive irrespective of the different antigen sources. The data
      show that DAT can be a useful addition to the diagnosis of ECL.

PMID- 12007443
TI  - High prevalence of nalidixic acid resistant, ciprofloxacin susceptible phenotype
      among clinical isolates of Escherichia coli and other Enterobacteriaceae.
AB  - Therapeutic failure of infections during their treatment with quinolones has been
      often described. This may be due to the development of resistance during
      treatment of an infecting strain which already had diminished susceptibility to
      quinolones, even though the initial MIC did not exceed the breakpoint. In this
      study the prevalence of the nalidixic acid resistant, ciprofloxacin susceptible
      phenotype among Enterobacteriaceae was analyzed. The results showed that 113 out
      of 151 (74.83%) strains of the Enterobacteriaceae with diminished susceptibility
      to ciprofloxacin (MICs from 0.06 to 1 microg/ml) were resistant to nalidixic acid
      (MICs > 32 microg/ml). The Escherichia coli strains presenting this phenotype
      already have a mutation in the amino acid codon Ser-83 of the gyrA gene, so that
      the possibility of developing a second mechanism of resistance during treatment
      is very high.

PMID- 12007444
TI  - Possible overestimation of penicillin resistant Streptococcus pneumoniae
      colonization rates due to misidentification of oropharyngeal streptococci.
AB  - Standard identification of Streptococcus pneumoniae by optochin and bile
      solubility testing can lead to ambiguous results for certain isolates. Newer
      bacteriologic identification techniques (e.g., DNA probes) now exist. In a
      prospective point prevalence study of oropharyngeal S. pneumoniae carriage rates
      among outpatients, we compared standard organism identification techniques to DNA
      probe testing. By standard identification criteria, 35 (4%) of 872 isolates were
      characterized as presumptive S. pneumoniae. Thirty of 35 presumptive isolates
      were recoverable for DNA probing; 9 (30%) presumptive isolates were confirmed
      using a DNA probe. The antimicrobial susceptibility pattern of these DNA probe
      positive isolates closely paralleled that of clinical blood isolates of S.
      pneumoniae obtained during the study period. The 21 (70%) DNA probe negative
      isolates, which may represent phylogenetically related species (such as S. mitis
      or S. oralis), had significantly reduced antimicrobial susceptibility patterns
      when compared with the DNA probe positive isolates. In colonization studies, if
      classic criteria (optochin disc zone and bile solubility) are the sole means of
      identification, S. pneumoniae penicillin resistance rates may be over-reported.

PMID- 12007445
TI  - In vitro susceptibility of vancomycin-resistant enterococci (VRE) to fosfomycin.
AB  - We evaluated the in vitro activity of fosfomycin against 75 clinical isolates of
      vancomycin-resistant enterococci (VRE). Using the NCCLS breakpoint for
      susceptibility of urinary tract isolates to fosfomycin (MIC > or = 256), 51 out
      of 52 Enterococcus faecium and all Enterococcus faecalis isolates tested were
      susceptible or intermediate to fosfomycin.

PMID- 12007446
TI  - A PCR assay for rapid detection of vancomycin-resistant enterococci.
AB  - Since the first report of a vancomycin-resistant enterococcal clinical isolate,
      these Gram-positive bacteria have emerged as important nosocomial pathogens.
      Several glycopeptide resistance phenotypes can be distinguished on the basis of
      the level and inducibility of resistance to vancomycin and teicoplanin. In the
      present study, we developed a multiplex PCR, which allows the simultaneous
      identification of enterococci at the genus level and detection of the most
      frequent glycopeptide resistance genotypes. Five primer sets targeting the genes
      vanA, vanB, vanC1, vanC2/C3 and tuf were used in one reaction tube with bacterial
      DNA extracted from three to five colonies. This PCR method is suitable for the
      rapid detection of vancomycin-resistant enterococci.

PMID- 12007447
TI  - Evaluation of an anti-PBP 2a slide latex agglutination test in coagulase-negative
      staphylococci isolated in Greek hospitals.
AB  - Oxacillin resistance was examined in 258 coagulase-negative staphylococci from
      Greek hospitals. mecA DNA was detected in 168 isolates, which were also resistant
      to oxacillin by agar dilution and disk diffusion, according to the current NCCLS
      breakpoints. Both methods exhibited a relatively low specificity misclassifying
      21 and 19 of the 90 mecA-negative isolates respectively as oxacillin resistant.
      In contrast, an anti-PBP 2a latex agglutination test, applied after induction by
      oxacillin, correctly classified 163 mecA-positive (sensitivity 97%) and 88 mecA
      negative isolates (specificity 97.7%).

PMID- 12007448
TI  - Emerging elevated mupirocin resistance rates among staphylococcal isolates in the
      SENTRY Antimicrobial Surveillance Program (2000): correlations of results from
      disk diffusion, Etest and reference dilution methods.
AB  - Staphylococci cause one-third of all serious invasive infections in the SENTRY
      Antimicrobial Surveillance Program including bacteremias and lower respiratory
      tract infections. Staphylococci are also commensals of the skin and nasal
      passages; therefore, topical agents active against these organisms are valuable
      in preventing infections or transfer of the organisms between patients and/or
      health care workers. Mupirocin is a potent topical anti-staphylococcal compound,
      but its effectiveness has been compromised by emerging resistance. In early 2000,
      the SENTRY Program detected 302 mupirocin-resistant isolates (131 Staphylococcus
      aureus, and 171 coagulase-negative staphylococci [CoNS]) from the United States
      (19/25 medical centers), Canada (4/5), Latin America (3/9) and Europe (7/18). One
      hundred sixty-eight mupirocin-resistant and 59 susceptible isolates were tested
      further by reference MIC, Etest (AB BIODISK, Solna, Sweden) and disk diffusion (5
      microg) methods. Mupirocin resistance rates for blood stream infections varied by
      geographic area: for S. aureus from 1.9 to 5.6%, and for CoNS from 12.8 to 39.9%.
      Using elevated mupirocin MIC results, two resistant populations were noted: low
      level resistance at 8-128 microg/mL and high-level resistance at > or = 1024
      microg/mL. Acceptable correlation was observed between Etest and disk diffusion
      results (r = 0.84) without serious intermethod interpretive errors. High-level
      resistant isolates had heavy growth with no visible zone around the disk; low
      level resistant isolates produced hazy zones of inhibition, and susceptible
      strains had clear zones of inhibition at > or = 17 mm. As mupirocin resistance
      can be plasmid-mediated, the prudent and appropriate use of this topical agent is
      important to minimize the ongoing development of resistance. Local surveillance
      for emerging mupirocin resistance appears warranted particularly in the United
      States and Canada, pragmatically using a disk diffusion test screening. Where
      more precise data are needed, the Etest is a very accurate method for
      distinguishing mupirocin low-level from high-level resistance patterns.

PMID- 12007449
TI  - Oxacillin susceptibility testing of coagulase-negative staphylococci using the
      disk diffusion method and the Vitek GPS-105 card.
AB  - One hundred and ninety-three isolates of coagulase-negative staphylococci (CoNS)
      were tested against oxacillin by agar dilution, disk diffusion, and Vitek (GPS
      105 card), and the presence of the mecA gene determined by multiplex PCR. The
      results obtained by all testing methods were in agreement for 190 isolates. Two
      mecA-negative isolates (S. lugdunensis and S. haemolyticus) had MICs of < or =
      0.25 microg/ml by agar dilution and Vitek but were resistant by disk diffusion.
      One mecA-positive isolate was resistant by Vitek and disk diffusion but had an
      agar dilution MIC of < or = 0.25 microg/ml. For the species of CoNS tested,
      oxacillin susceptibility results obtained with the Vitek GPS-105 card and disk
      diffusion correlated well with results obtained by National Committee for
      Clinical Laboratory Standards agar dilution and with the presence of the mecA
      gene.

PMID- 12007451
TI  - Stress activation of glutamate neurotransmission in the prefrontal cortex:
      implications for dopamine-associated psychiatric disorders.
AB  - In most psychiatric disorders, stress is the major nongenomic factor that
      contributes to the expression or exacerbation of acute symptoms, recurrence or
      relapse after a period of remission, and treatment outcome. Delineation of
      mechanisms by which stress contributes to these processes is fundamental to
      understanding the disease process and for improving outcome. In this article,
      evidence is reviewed to indicate that many central aspects of stress response,
      including activation of the hypothalmic-pituitary-adrenal (HPA) axis and dopamine
      neurotransmission, are modulated, and in some cases mediated, by glutamate
      neurotransmission in the prefrontal cortex (PFC). It is suggested that activation
      of glutamatergic neurotransmission in the PFC presents a common mechanism by
      which stress influences normal and abnormal processes that sustain affect and
      cognition. Although monoamines, in particular dopamine, have been considered the
      major culprits in the adverse effects of stress in disorders such as addiction
      and schizophrenia, it is likely that in a vulnerable brain with an underlying PFC
      pathophysiology, abnormal stress-activated monoaminergic neurotransmission is
      secondary to anomalies in cortical glutamate neurotransmission. Thus,
      understanding the contribution of glutamate-mediated processes to stress response
      through the use of experimental models that involve disrupted PFC function can
      provide insights to the fundamental pathophysiology of stress-sensitive
      psychiatric disorders and lead to novel strategies for treatment and prevention.

PMID- 12007452
TI  - An association of CAG repeats at the KCNN3 locus with symptom dimensions of
      schizophrenia.
AB  - BACKGROUND: In 1999 Cardno et al reported that long CAG repeats in the calcium
      activated potassium channel gene hSKCa3/KCNN3 are associated with higher negative
      symptom dimension scores in schizophrenia patients. There has been no attempt to
      replicate the results. In this study, we investigated whether a symptom
      polymorphism of schizophrenia is associated with both the CAG repeat numbers and
      the difference in allele sizes. METHODS: We tested the association of CAG repeats
      with symptom models of schizophrenia in 117 unrelated Jewish patients. A
      multivariate analysis (MANOVA) of two models of schizophrenia with the repeat
      distribution and the difference in allele sizes was performed. RESULTS: We found
      a significant positive association of the number of CAG repeats with negative
      syndrome, anergia, activation, and paranoid symptoms. In addition, nonparanoid
      schizophrenia patients who had differences in allele sizes were characterized by
      earlier onset of illness. CONCLUSIONS: The study supports the hypothesis that the
      combined effect of long CAG repeats and the differences in allele sizes
      contribute to symptom expression of schizophrenia, particularly on the anergia
      activation-paranoid axis.

PMID- 12007453
TI  - Neurotensin receptor binding abnormalities in the entorhinal cortex in
      schizophrenia and affective disorders.
AB  - BACKGROUND: Convergent evidence from in vivo and in vitro studies of
      schizophrenia have implicated the mesial temporal lobe as a primary site of
      pathological change in this disorder. We have previously reported decreased
      neurotensin receptor density in layer II of the intermediate entorhinal cortex
      (ERC) in schizophrenia, a finding seen elsewhere but not seen in more caudal ERC.
      METHODS: To study neuroanatomic and diagnostic specificity, we measured the
      density of neurotensin receptors in the intermediate and caudal ERC and
      hippocampal formation of schizophrenic, affective disorder control subjects, and
      normal control subjects. Slide-based radioligand binding was used to perform
      these studies. RESULTS: Not only schizophrenic but also affective disorder
      subjects had decreased neurotensin receptor density in layer II of the
      intermediate ERC. Affective disorder subjects had significantly decreased
      neurotensin receptor density in layers V/VI of the intermediate ERC, and
      schizophrenic subjects trended in the same direction. CONCLUSIONS: These findings
      demonstrate region-specific changes in neurotensin receptor binding levels in the
      mesial temporal lobe; however, there is no clear diagnostic specificity for these
      changes, because they were seen to varying degrees in both schizophrenia and
      affective disorders.

PMID- 12007454
TI  - Basal ganglia volumes in first-episode schizophrenia and healthy comparison
      subjects.
AB  - BACKGROUND: Previous studies suggest that dysfunction of cortico-striato-pallido
      thalamic (CSPT) circuitry may be involved in the pathophysiology of schizophrenia
      but also show that basal ganglia structure is highly plastic and may be
      influenced by antipsychotic treatments. Controversy remains about whether basal
      ganglia pathology can be detected in vivo among treatment-naive patients. We
      conducted a magnetic resonance imaging (MRI) study to examine basal ganglia
      structures and the limbic forebrain in first episode schizophrenia and healthy
      comparison subjects. METHODS: Fifty-one patients with first-episode schizophrenia
      and 28 healthy comparison subjects participated in the study. A high-resolution,
      special contrast (white matter nulling) MRI sequence was used to measure the
      caudate nucleus, nucleus accumbens, putamen, and subcommissural limbic forebrain.
      RESULTS: Volumes of the basal ganglia regions of interest (adjusted for total
      brain volume and age) did not differ significantly between the groups. Age
      correlated significantly with caudate and putamen volumes bilaterally in the
      healthy comparison group, but not among patients. CONCLUSIONS: The findings
      suggest that there are no volumetric abnormalities in basal ganglia before
      treatment in first-episode schizophrenia. The lack of a negative correlation
      between age and striatal volume among patients may implicate illness-associated
      factors that alter normal age-related changes in basal ganglia size.

PMID- 12007455
TI  - Odor identification, eye tracking and deficit syndrome schizophrenia.
AB  - BACKGROUND: Deficit syndrome (DS) schizophrenia patients have smooth pursuit eye
      movement (SPEM) dysfunction. We examined if they also had smell identification
      deficits, since social affiliation is related to olfaction in other mammals.
      METHODS: Sixty-seven patients had DS assessments: 31 patients had SPEM and 50 had
      Smell Identification Test (SIT) assessments, and 14 patients had both
      measurements. RESULTS: DS patients had worse SPEM and SIT performance than the
      non-DS patients. Areas under the receiver-operator characteristic (ROC) curves
      for SIT and SPEM were both fairly accurate in identifying the DS. The odds ratio
      (OR) for the DS for impaired versus normal SPEM was 6.21 (95% confidence interval
      [CI]: 1.21, 32.25) and for microsmia versus normosmia was 10.4 (95% CI: 1.23,
      88.18). Further analyses showed that the association of SIT with both SPEM and
      the DS could account for the SPEM-DS association. CONCLUSIONS: We found a strong
      association between the DS and SIT scores suggesting that the neural substrates
      of olfaction may be related to social affiliation in humans, as they are in other
      mammals. These data further support the notion that the DS defines a homogeneous
      subgroup of schizophrenia patients and further suggest that dysfunction in the
      neural circuitry of olfaction may contribute to its pathophysiology.

PMID- 12007456
TI  - Schizophrenic subjects show deficient inhibition but intact task switching on
      saccadic tasks.
AB  - BACKGROUND: Schizophrenic patients have executive function deficits, presumably
      on the basis of prefrontal cortex dysfunction. Although they consistently show
      impaired inhibition, the evidence of a task switching deficit is less consistent
      and is often based on performance of neuropsychological tests that require
      several cognitive processes (e.g., the Wisconsin Card Sort Test [WCST]). We
      investigated inhibition and task switching using saccadic tasks to determine
      whether schizophrenic patients have selective impairments of these executive
      functions. METHODS: Sixteen normal and 21 schizophrenic subjects performed blocks
      of randomly mixed prosaccade and antisaccade trials. This gave rise to four trial
      types: prosaccades and antisaccades that were either repeated or switched.
      Response accuracy and latency were measured. Schizophrenic subjects also
      performed the WCST. RESULTS: Schizophrenic subjects showed abnormal antisaccade
      and WCST performance. In contrast, task switching was normal and unrelated to
      either antisaccade or WCST performance. CONCLUSIONS: The finding of intact task
      switching performance that is unrelated to other measures of executive function
      demonstrates selective rather than general impairments of executive functions in
      schizophrenia. The findings also suggest that abnormal WCST performance is
      unlikely to be a consequence of deficient task switching. We hypothesize that
      inhibition and task switching are mediated by distinct neural networks, only one
      of which is dysfunctional in schizophrenia.

PMID- 12007457
TI  - Abnormalities of thalamic volume and shape detected in fetally irradiated rhesus
      monkeys with high dimensional brain mapping.
AB  - BACKGROUND: Prior research has indicated neuroanatomical abnormalities of the
      thalamus in schizophrenia. To study the possible pathogenesis, an animal model of
      neurodevelopmental thalamic damage has been developed by applying low-dose
      radiation to rhesus monkeys in early gestation. Irradiated monkeys sacrificed as
      infants demonstrate neuronal losses in specific thalamic nuclei and decreases in
      cortical neuropil. METHODS: Magnetic resonance scans were collected in adult
      Rhesus monkeys exposed to irradiation during thalamic neurogenesis (E33-42),
      after thalamic neurogenesis (E70-81), and in nonirradiated control animals. High
      dimensional brain mapping was used to compare thalamic volumes and shape
      characteristics in the three groups of animals. RESULTS: Animals exposed to
      irradiation at E33-42 showed a significant bilateral loss of thalamic volumes (>
      20%) compared with controls and with animals irradiated at E70-81 when total
      brain volume was used as a covariate in the analysis. Thalamic volume loss was
      associated with a nonuniform deformation of thalamic shape. CONCLUSIONS: A first
      trimester, neurodevelopmental insult in the nonhuman primate during thalamic
      neurogenesis produces a complex pattern of thalamic volume loss and shape
      deformation in adulthood. Low-dose irradiation of the fetal primate may be useful
      for modeling key features of the pathology described in schizophrenic patients.

PMID- 12007458
TI  - Two-dimensional versus three-dimensional cell counting.

PMID- 12007459
TI  - About assumptions in estimation of density of neurons and glial cells.

PMID- 12007461
TI  - The mechanism of Zn-phthalocyanine photosensitized lysis of human erythrocytes.
AB  - The phthalocyanines have recently been suggested as one of most effective
      possible sensitizers for photodynamic therapy and the blood viral inactivation.
      The further characterisation of the mechanism of human red blood cell lysis and
      membrane alterations upon photodynamic treatment in the presence of Zn
      phthalocyanine was the aim of this study. It was found that there were (2.7+/
      0.4).10(7) dye binding sites per red blood cell with the association constant
      equal to (1.4+/-0.3).10(4) M(-1). Two types of the photosensitized haemolysis:
      haemolysis during irradiation ("light" haemolysis) and post-irradiation
      haemolysis ("dark" haemolysis) were studied. The erythrocyte membrane
      hyperpolarisation, membrane fluidisation and cell swelling preceded the "light"
      haemolysis. The modification of the erythrocyte membrane band 3 protein by DIDS
      (an inhibitor of anion exchange) increased the rate of the "light" haemolysis.
      The rate of "dark" haemolysis was higher and that of "light" haemolysis was lower
      in potassium media in comparison to sodium ones. The rates of photohaemolysis
      depended on the erythrocyte membrane potential: a decrease of membrane potential
      inhibited both types of haemolysis. The cell shrinkage in the presence of sucrose
      (up to 15 mM) inhibited the "dark" haemolysis but significantly increased the
      "light" haemolysis. Oxidation of intracellular oxyHb to metHb by nitrite, which
      drastically decreases intracellular oxygen concentration, as well as GSH
      concentration, inhibited the rate of the "light" haemolysis. The results allow
      for the conclusion that the mechanism of photochemical ("light") haemolysis is
      not of a colloid-osmotical type, in contrast to the post-irradiation ("dark")
      haemolysis. The photochemical oxidation or denaturation of band 3 protein plays a
      significant role in the formation of haemolytic holes. The membrane lipid
      peroxidation, as well as glutathione oxidation, does not participate in the
      process of photosensitized haemolysis. From the inhibition of "dark" haemolysis
      by sucrose the apparent pore radius was estimated to be about 1.1 nm. The pores
      appear to be transient short-lived ones, the average pore number per cell was
      0.02.

PMID- 12007462
TI  - Protoporphyrin IX fluorescence kinetics in UV-induced tumours and normal skin of
      hairless mice after topical application of 5-aminolevulinic acid methyl ester.
AB  - Accumulation of protoporphyrin IX (PpIX) was investigated in normal skin and UV
      induced tumours in hairless mice after topical application of a cream containing
      2, 8 or 16% of 5-aminolevulinic acid methyl ester (ALA-Me). Higher levels of PpIX
      were measured in tumours compared to normal skin. The maximal amount of PpIX was
      reached at 1.5, 3 and 4 h after 2, 8 and 16% ALA-Me application, respectively.
      Higher tumour to normal skin PpIX fluorescence ratios were measured after
      application of 8 and 16% ALA-Me than after application of 2%. After irradiation
      with a broad spectrum of visible light from a slide projector, more than 90% of
      PpIX was bleached by fluences of 36 and 48 J/cm2, at fluence rates of 10 and 40
      mW/cm2 respectively. At these fluences, the PpIX photobleaching rate was
      significantly higher (P<0.05) in normal mouse skin than in tumours. In addition,
      for a given fluence, more PpIX was photobleached at the lower fluence rate (10
      mW/cm2) than at the higher fluence rate (40 mW/cm2) in normal skin (P<0.001) as
      well as in tumours (P<0.05) after exposure to 24 J/cm2 of light. In conclusion,
      the highest tumour to normal skin PpIX ratio was observed 3 h after application
      of 8% ALA-Me, suggesting that light exposure should be performed at this time in
      order to achieve an optimal PDT effect in this tumour model.

PMID- 12007463
TI  - Photochromic nucleic base units suitable for nucleic acid labelling.
AB  - New molecules incorporating a uracil nucleic base and a dihydroindolizine (DHI)
      unit linked via spacer arms, i.e., uracil-spyrodihydroindolizine (4), were
      synthesised as models for light sensitive systems for nucleic acid labelling. The
      uracil-DHI (4) undergoes easy photocoloration to the uracil-betaine (5)
      generating the UV-detectable species. Preliminary results show rather weak
      binding of uracil-DHI (4) to calf thymus-DNA.

PMID- 12007464
TI  - Indirect detection of photosensitizer ex vivo.
AB  - Photodynamic therapy induces the production of reactive oxygen species (ROS)
      within tissues exposed to laser light after administration of a sensitizer. In
      the context of continuing clinical and commercial development of chemicals with
      sensitizing properties, a minimally invasive assay is needed to determine the
      tissue kinetics of fluorescent or non-fluorescent photoreactive drugs. The level
      of ROS was determined ex vivo from 1 mm3 biopsy samples using 2'-7'
      dichlorofluorescin diacetate (DCFH-DA), a fluorescent probe which was converted
      into highly fluorescent dichlorofluorescein (DCF) in the presence of ROS. This
      assay was tested on meta(tetrahydroxyphenyl)chlorin (m-THPC, FOSCAN), a powerful
      and fluorescent sensitizer, and bacteriochlorophyll derivative WST09 (TOOKAD), a
      near-infrared absorbing sensitizer that is only slightly fluorescent. In
      conjunction with the ROS assay, the tissue accumulation of m-THPC was determined
      on biopsy samples using an optic fibre spectrofluorometer (OFS). DCF fluorescence
      was proportional to the level of oxidation induced by horseradish peroxidase used
      as a control and to the concentration (range: 0-5 microg x ml(-1)) of both
      selected photosensitizers irradiated in a tube together with DCFH. Regardless of
      the organ studied, an excellent correlation was found between fluorescence
      measurement by OFS and ROS determination for m-THPC. m-THPC (2 mg x kg(-1) iv)
      accumulation in tumour tissues was best after 48 h, and the best signal was
      obtained in liver. With non-fluorescent WST09 (2 mg x kg(-1)), ROS determination
      showed the best tumour uptake 48 h after injection, with a tumour/muscle ratio of
      5.4. The ROS assay appears to be feasible for determining sensitizer
      concentration in regular grip biopsy tissue samples.

PMID- 12007465
TI  - Xenon chloride ultraviolet B laser is more effective in treating psoriasis and in
      inducing T cell apoptosis than narrow-band ultraviolet B.
AB  - Earlier we reported that a 308-nm xenon chloride (XeCl) UVB laser is highly
      effective for treating psoriasis. As ultraviolet B light seems to cause T cell
      apoptosis, in the present study we studied the ability of the XeCl laser to
      induce T-cell apoptosis in vitro, and then compared the apoptosis-inducing
      capacities of narrow-band UVB (NB-UVB) light and the XeCl laser. The role of
      laser impulse frequency and intensity in the therapeutical and apoptosis-inducing
      efficacy of XeCl laser was also investigated. Both XeCl laser and NB-UVB induced
      T cell apoptosis, but quantitative induction was greater with XeCl laser. Changes
      in the frequency and intensity of impulses of XeCl laser did not influence its
      therapeutic and T cell apoptosis-inducing efficacy. These results suggest that
      the more effective induction of T cell apoptosis can be responsible for the
      greater clinical efficacy of XeCl laser compared to NB-UVB. Additionally, the
      optical properties of the XeCl laser (a monochromatic, coherent, pulse-mode
      laser; easier precise dosimetry, there are no 'contaminating' wavelengths) can
      make this laser light an ideal tool for studies of the mode of action of UVB
      light.

PMID- 12007466
TI  - Fluorescence investigation of the recombinant cyanobacterial phytochrome (Cph1)
      and its C-terminally truncated monomeric species (Cph1Delta2): implication for
      holoprotein assembly, chromophore-apoprotein interaction and photochemistry.
AB  - Recombinant dimeric full-length Cph1 holophytochrome and its C-terminally
      truncated monomeric species [Cph1Delta2, comprising the chromophore-bearing N
      terminal sensory module (residues 1 to 514)] from the cyanobacterium
      Synechocystis expressed in E. coli and reconstituted in vitro with
      phycocyanobilin (PCB) were investigated with the use of fluorescence spectroscopy
      and photochemistry in the temperature range from 85 to 293 K. Holoprotein
      assembly in Cph1 apparently proceeds via intermediate states with the emission
      maximum at 680-690 nm (I685) and 700 nm (I700) and a half-life time, at room
      temperature, of < or =5 s. Conversion of the putative I685 into mature Cph1
      involves relaxation of the chromophore into a more flexible conformation. Cph1
      and Cph1Delta2 were closely similar in their spectroscopic and photochemical
      characteristics (position of the emission band and its width, character of the
      temperature dependence of the fluorescence and activation energy of the
      fluorescence decay, kinetics and extent of the Pr conversion at low and ambient
      temperatures), suggesting that there is no immediate effect of the C-terminus on
      the photochemical properties of the chromophore in Cph1 and that chromophore
      chromophore interactions in the dimer are not significant. The latter is also
      supported by the lack of energy transfer from the phycoerythrobilin (PEB) to PCB
      in the mixed PEB/PCB adduct of Cph1. At the same time, certain variations in the
      fluorescence and photochemical parameters of Cph1 with temperature of the sample
      and intensity of the excitation light and dependence of the emission spectra on
      excitation wavelength were observed. These variations are interpreted as a
      manifestation of the Cph1 heterogeneity which may be due to the existence of
      different conformers of the chromophore and photoproduct formation under
      excitation light.

PMID- 12007467
TI  - Phase-resolved fluorescence study of mono-L-aspartyl chlorin E6.
AB  - The properties of a photosensitizer for photodynamic therapy, mono-L-aspartyl
      chlorin e6 (NPe6), were investigated using phase-resolved fluorescence. NPe6 was
      analyzed in water solution at concentrations ranging from 3.13x10(-7) to 8.00x10(
      5) M. The photophysical parameters of the lowest singlet excited state of NPe6
      molecules were experimentally determined. It was confirmed that NPe6 molecules
      were in the isolated molecular state at concentrations below 1.00x10(-5) M. It
      was also confirmed that the fluorescence in this concentration range was
      ascribable to the electronic transition of isolated NPe6 molecules from the
      lowest singlet excited state to the ground state. At concentrations above
      1.00x10(-5) M, some of the NPe6 molecules formed dimers in water solution, which
      caused a red shift of the fluorescence spectrum and an enhancement of
      fluorescence in the 700-750 nm wavelength region. Semiempirical molecular orbital
      calculation revealed that the sodium aspartate attached to the tetrapyrrole ring
      through the ethanoic group was remarkably bent with respect to the tetrapyrrole
      plane. This bending appeared to hinder the formation of NPe6 dimers at
      concentrations up to 1.00x10(-5) M.

PMID- 12007468
TI  - Nonradiative deactivation of the electronic excitation energy in cyanine dyes:
      influence of binding to DNA.
AB  - The processes of nonradiative deactivation of electronic excitation energy in
      cyanine dyes determine their quantum yield. Because of that, the study of the
      influence of cyanines binding to DNA on these processes can provide information
      on the causes leading to the cyanines fluorescence intensity enhancement in the
      presence of DNA. In the presented paper, the activation energies of nonradiative
      degradation of electronic excitation, quantum yields and rate constants of
      nonradiative transitions of several cyanines in free state and in the presence of
      DNA were established and compared. The mechanisms of nonradiative deactivation of
      dye excitation energy were discussed.

PMID- 12007469
TI  - Active oxygen species (1O2, O2*-) generation in the system of TiO2 colloid
      sensitized by hypocrellin B.
AB  - TiO2 semiconductor colloids have been successfully employed in environmental
      clean-up, antibacterial and bactericidal action under ultraviolet light due to
      its strong redox ability and high yield of active oxygen species (1O2, O2*-),
      *OOH) generation. Hypocrellin B, isolated from Hypocrella bambusae (B.et.Br)
      Sacc, a natural pigment with strong and broad absorption over the visible light
      region, was used in our work in an attempt to extend the photoresponse of TiO2 to
      visible light and maintain the high generation of active oxygen under visible
      light illumination. The formation of the HB-TiO2 chelate was characterized by UV
      Vis and surface enhanced raman spectroscopy (SERS) and it was found that the
      chelate still had high efficiency of active oxygen generation. The possible
      generation mechanism was explored by Electron Paramagnetic Resonance (EPR) and
      time-resolved transient spectra techniques, showing that singlet oxygen (1O2) and
      superoxide radical anion (O2*-)) were produced via energy transfer and electron
      transfer, respectively. The application of HB-TiO2 chelate in environment
      protection and bacteria sterilization was implied.

PMID- 12007470
TI  - 1,5-Anhydro-D-fructose; a versatile chiral building block: biochemistry and
      chemistry.
AB  - There is a steadily increasing need to expand sustainable resources, and
      carbohydrates are anticipated to play an important role in this respect, both for
      bulk and fine chemical preparation. The enzyme alpha-(1-->4)-glucan lyase
      degrades starch to 1,5-anhydro-D-fructose. This compound, which has three
      different functional properties, a prochiral center together with a permanent
      pyran ring, renders it a potential chiral building block for the synthesis of
      valuable and potentially biologically active compounds. 1,5-Anhydro-D-fructose is
      found in natural materials as a degradation product of alpha-(1-->4)-glucans. The
      occurrence of lyases and the metabolism of 1,5-anhydro-D-fructose are reviewed in
      the biological part of this article. In the chemical part, the elucidated
      structure of 1,5-anhydro-D-fructose will be presented together with simple
      stereoselective conversions into hydroxy/amino 1,5-anhydro hexitols and a
      nojirimycin analogue. Synthesis of 6-O-acylated derivatives of 1,5-anhydro-D
      fructose substituted with long fatty acid residues is carried out using
      commercially available enzymes. Those reactions lead to compounds with potential
      emulsifying properties. The use of protected derivatives of 1,5-anhydro-D
      fructose for the synthesis of natural products is likewise reviewed. The
      potential utilization of this chemical building block is far from being
      exhausted. Since 1,5-anhydro-D-fructose now is accessible in larger amounts
      through a simple-enzyme catalyzed degradation of starch by alpha-(1-->4)-glucan
      lyase, the application of 1,5-anhydro-D-fructose may be considered a valuable
      contribution to the utilization of carbohydrates as the most abundant resource of
      sustainable raw materials.

PMID- 12007471
TI  - Influence of exo beta-D-galactofuranosidase inhibitors in cultures of Penicillium
      fellutanum and modifications in hyphal cell structure.
AB  - We have examined beta-D-galactofuranosidase production by Penicillium fellutanum
      in the presence of D-galactono-1,4-lactone or 4-aminophenyl 1-thio-beta-D
      galactofuranoside, two potent in vitro inhibitors of the enzyme. Activity of the
      enzyme in the culture filtrate was increased by 35% when glucose was replaced by
      D-galactose as the carbon source, and the activity diminished 80% of the control
      value when the inhibitors were added. Significant alterations of the culture were
      observed: (a) the medium became increasingly opalescent due to the secretion of a
      protein aggregate (PA) which contained 15% neutral sugar, mainly ribose; (b) the
      peptidophosphogalactomannan (pPGM) containing galactofuranose, normally produced
      by P. fellutanum, could not be obtained from the culture medium in the presence
      of the inhibitors; (c) the content of galactofuranose in the cell wall was
      significantly decreased in the presence of D-galactono-1,4-lactone. The influence
      on the mycelia growth was investigated by light microscopy (LM) and transmission
      electron microscopy (TEM) showing important alterations.

PMID- 12007472
TI  - Galactose dialdehyde as potential protein cross-linker: proof of principle.
AB  - Combined enzymatic oxidation of D-galactose by D-galactose oxidase [EC 1.1.3.9]
      in water, amination with butylamine, and oxalic acid catalyzed Amadori
      rearrangement in methanol yielded 1,6-bis(butylamino)-1,6-dideoxy-erythro-hexo
      2,5-diulose, demonstrating how in situ formed galacto-hexodialdose can be used to
      cross-link protein residues. The various species formed during this three-step
      conversion are present as bicyclic structures in solution as established by 13C
      labeling and in situ NMR spectroscopy of the reaction mixtures. Using protein
      (gelatin) instead of butylamine, distinct Amadori product formation was observed
      using 99% enriched D-(1-(13)C)- and D-(2-(13)C)-galactose.

PMID- 12007473
TI  - Conformational studies of blood group A and blood group B oligosaccharides using
      NMR residual dipolar couplings.
AB  - The conformations of two synthetic trisaccharides of blood group A and B (alpha-L
      Fucp-(1-->2)-[alpha-D-GalpNAc-(1-->3)]-alpha-D-Galp and alpha-L-Fucp-(1-->2)
      [alpha-D-Galp-(1-->3)]-alpha-D-Galp, respectively) and of a type A
      tetrasaccharide alditol, Fucp-(1-->2)-[alpha-D-GalpNAc-(1-->3)]-beta-D-Galp-(1-
      >3)-GalNAc-ol, were studied by NMR measurements of one-bond C-H residual dipolar
      couplings in partially oriented liquid crystal solutions. The conformations of
      the three oligosaccharides were analyzed by generating thousands of structures
      using a Monte-Carlo method. Two different strategies were applied to calculate
      theoretical dipolar couplings for these structures. In the first method, the
      orientation of the molecule was calculated from the optimal fit of the molecular
      model to the experimental data, while in the second method the orientation tensor
      was calculated directly from the moment of inertia of the molecular model. Both
      methods of analysis give similar results but with slightly better agreement with
      experiment for the former one. The analysis of the results implies a single
      unique conformation for both blood group epitopes in solution in disagreement
      with theoretical models suggesting the existence of two conformers in solution.

PMID- 12007474
TI  - Structural characterisation of the olive pomace pectic polysaccharide arabinan
      side chains.
AB  - An arabinan (97% of Ara and 3% of hexuronic acid) was isolated from the alcohol
      insoluble residue (AIR) of olive pomace by treatment with 0.02 M HNO(3), at 80
      degrees C, followed by graded precipitation with ethanol. It was separated from
      acidic pectic polysaccharides by anion-exchange chromatography, and by size
      exclusion chromatography its molecular weight was estimated as 8.4 kDa. By
      methylation analysis, the linkage composition was established as 5:4:3:1 for (1-
      >5)-Araf, T-Araf, (1-->3,5)-Araf and (1-->3)-Araf, respectively. 13C NMR
      spectroscopy confirmed this linkage composition, and allowed to assign the alpha
      anomeric configuration for the arabinofuranosyl residues, except for some
      terminally linked ones, that were seen to occur as T-beta-Araf. By 2D NMR
      spectroscopy (1H and 13C), it was possible to conclude that the T-beta-Araf was
      (1-->5)-linked to a (1-->5)-Araf residue. Also, in the arabinan (1-->5)-Araf
      backbone, the branched (1-->3,5)-Araf residues were always adjacent to linear (1-
      >5)-Araf residues. A tentative structure is proposed.

PMID- 12007475
TI  - Effect of (1-->3)- and (1-->4)-linkages of fully sulfated polysaccharides on
      their anticoagulant activity.
AB  - Chemically fully sulfated polysaccharides including xylan (-->4Xylbeta-(1-
      >4)Xylbeta1-->), amylose (-->4Glcalpha-(1-->4)Glcalpha1-->), cellulose (-
      >4Glcbeta-(1-->4)Glcbeta1-->), curdlan (-->3Glcbeta-(1-->3)Glcbeta1-->) and
      galactan (-->3Galbeta-(1-->3)Galbeta1-->), which have been isolated from Korean
      clam, were prepared, and their anticoagulant activity was investigated. The
      results strongly suggest that the activity might not be depending on anomeric
      configuration (alpha or beta) or monosaccharide species but on the glycosidic
      linkage, either (1-->3) or (1-->4). 1H NMR studies of these modified
      polysaccharides show that the neighboring sulfate groups at the C-2 and C-3
      positions might have caused the conformational changes of each monosaccharide
      from 4C(1) to 1C(4). Furthermore, the effect of 6-sulfate residues on the
      anticoagulant activity was investigated using a specific desulfated reaction for
      the chemically fully sulfated polysaccharides. The 6-sulfate group is very
      important in determining anticoagulant activity of (1-->3)-linked
      polysaccharides, whereas the activity is not affected by presence or absence of
      the 6-sulfate group in (1-->4)-linked polysaccharides.

PMID- 12007476
TI  - Hexasaccharides from the histamine-modified depolymerization of porcine
      intestinal mucosal heparin.
AB  - Specific sequences in heparin are responsible for its modulation of the
      biological activity of proteins. As part of a program to characterize heparin
      peptide and heparin-protein binding, we are studying the interaction of
      chemically discrete heparin-derived oligosaccharides with peptides and proteins.
      We report here the isolation and characterization, by one- and two-dimensional 1H
      NMR spectroscopies, of ten hexasaccharides, one pentasaccharide, and one
      octasaccharide serine that were isolated from depolymerized porcine intestinal
      mucosal heparin. Hexasaccharides were chosen for study because they fall within
      the size range, typically tetra- to decasaccharide in length, of heparin
      sequences that modulate the activity of proteins. The depolymerization reaction
      was catalyzed by heparinase I (EC 4.2.2.7) in the presence of histamine, which
      binds site specifically to heparin. Histamine increases both the rate and extent
      of heparinase I-catalyzed depolymerization of heparin. It is proposed that
      oligosaccharides produced by heparinase I-catalyzed depolymerization can inhibit
      the enzyme by binding to the imidazolium group of histidine-203, which together
      with cysteine-135 forms the catalytic domain of heparinase I. The increased rate
      and extent of depolymerization are attributed to competitive binding of the
      oligosaccharides by histamine.

PMID- 12007477
TI  - Synthesis of a globotetraose trimer.
AB  - The synthesis is described of a globotetraose trimer in 74% yield by the reaction
      of tris(2-aminoethyl)amine with the hydrophobic squaric decyl ester glycoside of
      globotetraose. The synthesis was readily monitored and purified using reversed
      phase HPLC. Unreacted squaric decyl ester globotetraoside was recovered rendering
      the method highly economical.

PMID- 12007478
TI  - An improved method for the preparation of 3-O-benzyl-6-O-pivaloyl-alpha-D
      glucopyranose 1,2,4-orthopivalate.
AB  - The synthetic route to 3-O-benzyl-6-O-pivaloyl-alpha-D-glucopyranose 1,2,4
      orthopivalate (1), which was previously established, was shortened by introducing
      two novel reactions, regioselective pivaloylation with dibutyltin oxide in
      toluene for the regioselective activation of hydroxyl groups, and intramolecular
      orthoesterification with benzenesulfonyl chloride and triethylamine in
      dichloromethane. Compound 1 was obtained in 58.8% overall yield from commercially
      available 1,2:5,6-di-O-isopropylidene-alpha-D-glucopyranose (2) via four reaction
      steps.

PMID- 12007479
TI  - 5,7-Diamino-5,7,9-trideoxynon-2-ulosonic acid: a novel sugar from a
      phytopathogenic Pseudomonas lipopolysaccharide.
AB  - Preliminary results on the structure of a novel sugar from a lipopolysaccharide
      from Pseudomonas corrugata, a plant pathogenic bacterium whose several aspects of
      phytopathogenic mechanism are under investigation, are described. This is a 5,7
      diamino-5,7,9-trideoxynon-2-ulosonic acid, isolated as an O-glycoside from the
      Smith degradation of the O-chain. The structure was obtained both with NMR and MS
      methodologies. To the best of our knowledge, this is the first example of 3
      hydroxylated non-2-ulosonic acid.

PMID- 12007480
TI  - Structure of the O-specific polysaccharide chain of the lipopolysaccharide of
      Bordetella hinzii.
AB  - The lipopolysaccharide of Bordetella hinzii was analyzed after various chemical
      degradations by NMR spectroscopy and MALDI mass spectrometry, and the following
      structure of the polysaccharide chain was determined: 4-O-Me-alpha-GalpNAc3NAcAN
      (1-->[-->4)-beta-GlcpNAc3NAcAN-(1-->4)-beta-GlcpNAc3NAcAN-(1-->4)-alpha
      GalpNAc3NAcAN-(1-](n)-where GlcNAc3NAcAN and GalNAc3NAcAN stand for 2,3
      diacetamido-2,3-dideoxy-glucuronamide and -galacturonamide, respectively. The
      polysaccharide chain is terminated with a 4-O-methylated GalNAc3NAcAN residue and
      is rather short (n < or = 5).

PMID- 12007481
TI  - A method for obtaining equilibrium tautomeric mixtures of reducing sugars via
      glycosylamines using nonaqueous media.
AB  - Equilibrium tautomeric mixtures of several mono- and disaccharides are obtained
      in anhydrous form, without the use of water, by reacting the commercially
      available reducing sugars with ammonia gas in dry methanol, followed by the
      concentration of the resultant solution to dryness. Mutarotation and hydrolysis
      of the initially formed glycosylamine in the resultant medium account for the
      transformation. Equilibrium anomeric mixtures enriched in the beta-form of
      commercially available sugars such as alpha-D-glucose and alpha-lactose have not
      only vastly increased solubility, but are also synthetically valuable as these
      can be readily converted to the methyl/benzyl/trimethylsilyl ether and other
      derivatives for further transformations.

PMID- 12007483
TI  - Engineering flax and hemp for an alternative to cotton.

PMID- 12007484
TI  - Cloning advances and challenges for conservation.
AB  - Although controversy surrounds cloning efforts, the cloning of animals to assist
      efforts to preserve genetic variation in support of endangered species
      conservation efforts has attracted serious interest. A recent report by Loi et
      al. describing the cloning of a mouflon (a species of wild sheep) in a domestic
      sheep surrogate points to potential conservation opportunities and additional
      challenges in the evaluation of appropriate technologies for present and future
      efforts to conserve gene pools of endangered species.

PMID- 12007490
TI  - Isochores: dream or reality?

PMID- 12007491
TI  - Biocatalysis: applications and potentials for the chemical industry.
AB  - The chemical industry is exploring the use of renewable feed stocks to improve
      sustainability, prompting the exploration of bioprocesses for the production of
      chemicals. Attractive features of biological systems include versatility,
      substrate selectivity, regioselectivity, chemoselectivity, enantioselectivity and
      catalysis at ambient temperatures and pressures. However, a challenge facing
      bioprocesses is cost competitiveness with chemical processes because capital
      assets associated with the existing commercial processes are high. The chemical
      industry will probably use biotechnology with existing feed stocks and processes
      to extract higher values from feed stocks, process by-products and waste streams.
      In this decade, bioprocesses that offer either a process or a product advantage
      over traditional chemical routes will become more widely used.

PMID- 12007492
TI  - Polycyclic aromatic hydrocarbons: environmental pollution and bioremediation.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widely distributed and relocated in
      the environment as a result of the incomplete combustion of organic matter. Many
      PAHs and their epoxides are highly toxic, mutagenic and/or carcinogenic to
      microorganisms as well as to higher systems including humans. Although various
      physicochemical methods have been used to remove these compounds from our
      environment, they have many limitations. Xenobiotic-degrading microorganisms have
      tremendous potential for bioremediation but new modifications are required to
      make such microorganisms effective and efficient in removing these compounds,
      which were once thought to be recalcitrant. Metabolic engineering might help to
      improve the efficiency of degradation of toxic compounds by microorganisms.
      However, efficiency of naturally occurring microorganisms for field
      bioremediation could be significantly improved by optimizing certain factors such
      as bioavailability, adsorption and mass transfer. Chemotaxis could also have an
      important role in enhancing biodegradation of pollutants. Here, we discuss the
      problems of PAH pollution and PAH degradation, and relevant bioremediation
      efforts.

PMID- 12007493
TI  - Stem-loop oligonucleotides: a robust tool for molecular biology and
      biotechnology.
AB  - The specific structural features of stem-loop (hairpin) DNA constructs provide
      increased specificity of target recognition. Recently, several robust assays have
      been developed that exploit the potential of structurally constrained
      oligonucleotides to hybridize with their cognate targets. Here, I review new
      diagnostic approaches based on the formation of stem-loop DNA oligonucleotides:
      molecular beacon methodology, suppression PCR approaches and the use of hairpin
      probes in DNA microarrays. The advantages of these techniques over existing ones
      for sequence-specific DNA detection, amplification and manipulation are
      discussed.

PMID- 12007494
TI  - Impact of targeted vector design on Co/E1 plasmid replication.
AB  - The demands for recombinant proteins, in addition to plasmid DNA, for therapeutic
      use are steadily increasing. Bacterial fermentation processes have long been and
      still are the major tool for production of these molecules. The key objective of
      process optimization is to attain a high yield of the required quality, which is
      determined, to a large extent, by plasmid replication rates, metabolic capacity
      and the properties of the specific gene construct. When high copy number plasmids
      are used, the metabolic capacity of the host cell is often overstrained and
      efficient protein production is impaired. The plasmid copy number is the key
      parameter in the exploitation of the host cell, and can be maximized by optimal
      control of the flux ratios between biosynthesis of host cell proteins and
      recombinant proteins.

PMID- 12007495
TI  - Analysis of protein phosphorylation using mass spectrometry: deciphering the
      phosphoproteome.
AB  - In signal transduction in eukaryotes, protein phosphorylation is a key event. To
      understand signaling processes, we must first acquire an inventory of
      phosphoproteins and their phosphorylation sites under different conditions.
      Because phosphorylation is a dynamic process, elucidation of signaling networks
      also requires quantitation of these phosphorylation events. In this article, we
      outline several methods for enrichment of phosphorylated proteins and peptides
      and discuss various options for their identification and quantitation with
      special emphasis on mass spectrometry-based techniques.

PMID- 12007496
TI  - Empowering patients with point-of-care testing.
AB  - Point-of-care testing (POCT) is becoming a major force in the future evolution of
      healthcare. It has the potential to expand further by increasing the
      accessibility, speed and accuracy of results. New developments in POCT technology
      will predictably occur in four areas: scope, connectivity, non-invasiveness and
      miniaturization. POCT test menus will continue to grow, wireless connectivity
      with automatic data capture will become the norm and non-invasive POCT will
      evolve into a wide range of sizes, shapes and functionalities.

PMID- 12007498
TI  - Bone marrow lymphoid aggregates in myelodysplastic syndromes: incidence,
      immunomorphological characteristics and correlation with clinical features and
      survival.
AB  - Lymphoid aggregates (LA) are a common finding in bone marrow biopsies but little
      is known about their clinical implications and biological significance. We found
      LA in 51/206 patients with myelodysplastic syndromes (MDS). There was no
      correlation with age, disease progression or overall survival. The group with LA
      had lower hemoglobin values (P=0.03), and was associated with an increase in
      reticulin fibres (P=0.01). Although they were more frequent in RAEB, this did not
      reach statistical significance. Most LA had a benign morphology and showed CD20
      expression in three distinct patterns: central, perinodular or diffuse. No
      evidence of an association with lymphoproliferative disease was observed. LA
      probably represent an ongoing immune stimulation and are probably related to an
      altered bone marrow microenvironment, with no impact on prognosis.

PMID- 12007500
TI  - Myelodysplastic syndrome in childhood: report of two cases with deletion of
      chromosome 4 and the Philadelphia chromosome.
AB  - We report two pediatric patients with unclassified myelodysplastic syndrome (MDS)
      by the French-American-British (FAB) group. Both cases had clinical and
      hematological peculiarities, which had not been described yet. The cytogenetic
      alterations were 4q deletion and the Philadelphia (Ph) chromosome which appeared
      at different moments of the disease. One patient showed the Ph chromosome at
      disease transformation and the other at diagnosis. The different breakpoints at
      4q and the presence of Ph could be a marker of this form of MDS. The association
      of clinical and hematological findings suggests the possibility of a new group of
      pediatric MDS.

PMID- 12007501
TI  - High-dose cytarabine as consolidation treatment for patients with acute myeloid
      leukemia with t(8;21).
AB  - Seventeen patients affected by acute myeloid leukemia (AML) with t(8;21) were
      prospectively programmed to receive three courses of high-dose cytarabine (HDARA
      C) as post-remission therapy. The median age was 39 years and in all cases
      t(8;21) was the only karyotypic abnormality. Complete remission (CR) was achieved
      in 14 out of 17 cases (82%) and, after first consolidation with NOVIA regimen
      (intermediate dose ARA-C plus mitoxantrone), all patients received the three
      planned courses of HDARA-C (3g/m(2) q12h on days 1, 3, 5). There were two
      documented infections, while all patients experienced fever of unknown origin
      (FUO). Nonhematological toxicity was mild. Thirteen out of 14 patients are in
      continuous CR after a median follow-up of 44 months. One patient relapsed at 16
      months and, following CR2 achievement, underwent allogeneic transplantation; he
      died 3 months later while in CR from acute graft versus host disease (GVHD).
      Survival at 5 years is projected at 79%. Our data confirm the efficacy of
      repeated courses of HDARAC for patients with t(8;21) AML.

PMID- 12007502
TI  - Minimal residual disease by metaphase FISH in children with ALL: clonal cells
      during or after chemotherapy may not predict relapse.
AB  - The evaluation of minimal residual disease (MRD) is increasingly gaining ground
      in the prognostic assessment of childhood acute lymphoblastic leukemia (ALL). We
      studied MRD by metaphase-fluorescent in situ hybridization (FISH) in 41 children
      with ALL. At diagnosis, all patients were karyotyped by standard G-banding and
      studied with comparative genomic hybridization (CGH). Standard cytogenetic
      preparations were used for FISH. Eleven children were FISH-positive at some point
      post-induction. One of the eleven had a bone marrow (BM) relapse, and another a
      central nervous system (CNS)-relapse at the end of maintenance therapy, while the
      others remain in continuous complete remission (CCR). Five of the eleven FISH
      positive were positive also after cessation of therapy, but none have relapsed.
      Of the 30 children with no FISH-detectable MRD post-induction, 2 have relapsed.
      We show that despite the presence of mitotically active blasts from the original
      leukemic clone during or after treatment, most of the children in our series
      remain in CCR although no action is taken to intensify or prolong the treatment.

PMID- 12007503
TI  - Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic
      syndrome.
AB  - Clonal expansion of leukemic cells is thought to be due to proliferation in
      excess of apoptosis. To define and compare proliferation and apoptosis between
      various leukemias and myelodysplastic syndrome (MDS), we measured proliferating
      cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation as
      surrogate markers for proliferation and caspase 3 activity and annexin V surface
      binding as surrogate markers for activation of the apoptotic cascade in patients
      with MDS, chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML),
      acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and
      chronic myeloid leukemia (CML). We found high proliferation in bone marrow cells
      from MDS and CMML as measured by PCNA and BrdU incorporation. The lowest level of
      proliferation was found in CLL. Apoptosis was also highest in MDS and CMML as
      measured by annexin V and caspase 3 activity. Unexpectedly, we found no
      significant difference in proliferation in bone marrow CD34+ cells from various
      leukemias or MDS. Apoptosis was significantly higher in bone marrow CD34+ cells
      from MDS and CML in chronic phase as compared to CD34+ cells from AML patients.
      Our results illustrate differences in proliferation and apoptosis between acute
      and chronic leukemias and MDS. These differences may have diagnostic and
      therapeutic implications.

PMID- 12007504
TI  - Engraftment and tumorigenesis of HTLV-1 transformed T cell lines in SCID/bg and
      NOD/SCID mice.
AB  - Human T cell leukemia/lymphoma virus type-1 (HTLV-1) is recognized as the
      etiological agent of adult T cell leukemia (ATL). Although HTLV-1 can immortalize
      human lymphocytes in culture, identification of molecular events leading to
      tumorigenesis after HTLV-1 infection remain elusive. SCID/bg and NOD/SCID mice
      have reduced natural killer (NK) cell activity and were inoculated
      intraperitoneally with HTLV-1 transformed cells to refine and characterize the
      SCID mouse as a small animal model for investigation of HTLV-1 tumorigenesis.
      HTLV-1 transformed cell lines originally derived by cocultivation of uninfected
      peripheral blood mononuclear cells (PBMC) with lethally irradiated leukemic cells
      from patient samples (SLB-1, MT-2 and HT-1-RV) were lymphomagenic when inoculated
      into NOD/SCID mice. In contrast, immortalized cell lines generated by
      transfection PBMC with an infectious molecular clone of HTLV-1 (ACH or ACH.p12)
      were not tumorigenic. The differing behaviors of HTLV-1 infected cell lines in
      NOD/SCID mice indicates that viral infection and immortalization of human PBMC
      for growth in culture is not sufficient for induction of a tumorigenic phenotype.
      The higher level of engraftment of HTLV-1 transformed cell lines in NOD/SCID mice
      suggests that this is an effective animal model to investigate molecular
      determinants of HTLV-1 lymphomagenesis.

PMID- 12007505
TI  - Expression of cell surface NM23 proteins of human leukemia cell lines of various
      cellular lineage and differentiation stages.
AB  - Cell surface expression of NM23 protein is only observed on tumor cell lines, but
      not on normal cells. To examine what types of tumor cell line express the cell
      surface NM23 protein, we measured the cell surface NM23-H1 and NM23-H2 proteins
      of leukemia line cells on various cellular lineage and differentiation stages.
      The NM23-H1 was expressed on myeloid leukemia lines but not lymphoid lines, while
      NM23-H2 was only expressed on erythroleukemia lines. The complement-dependent
      cytolysis confirmed the expression of these proteins on the surface. Surface NM23
      H1 and NM23-H2 proteins were decreased during in vitro erythroid and granulocyte
      differentiation. These results show that the surface expression of NM23 proteins
      is related to cellular lineage and differentiation stage of leukemia line cells.

PMID- 12007506
TI  - Interleukin-12-induced cytotoxicity against syngeneic B cell lymphomas of SJL/J
      mice.
AB  - The B cell lymphomas (RCS) that develop spontaneously in 90% of aging SJL/J mice
      stimulate syngeneic CD4+ Vbeta16+ Th2 cells to produce cytokines, such as IL-4
      and IL-5, which promote lymphoma growth. Although RCS cells express a unique
      superantigen (vSAg) encoded by an endogenous MMTV (Mtv-29) provirus that also
      elicits IFN-gamma production from naive syngeneic lymphoid cells, there is no
      development of RCS-specific cytotoxicity. However, addition of IL-12 to co
      cultures of SJL spleen and irradiated (gamma-)RCS cells resulted in the
      appearance of effector cells that killed RCS and NK-susceptible target cells.
      Antibody depletion studies revealed at least two types of RCS/IL-12-induced
      cytotoxic cells: (1) NK cells (Asialo GM1+) and (2) CD8+ CTL. Despite high titers
      of IFN-gamma in the SN of co-culture of SJL spleen and gamma-RCS cells,
      cytotoxicity only developed if IL-12 was also included in the co-cultures. The
      results of RNAse protection assays and multi-parameter FACS analysis demonstrated
      an upregulation of IFN-gamma and decrease in IL-4 by activated Th cells in co
      cultures with IL-12. These results indicate that inclusion of IL-12 in primary co
      cultures of SJL spleen and gamma-RCS cells influences the qualitative nature of
      the response to favor use of RCS-responsive Th1 rather than Th2 cells to
      facilitate the production of cytotoxic effector cells. Results of in vivo
      experiments support this hypothesis, as judged by tumor growth assays and FACS
      analysis of the tumor cell content of lymphoid tissues. Inhibition of lymphoma
      growth was observed in mice given gamma-RCS/IL-12-induced effector cells prior to
      injection of viable RCS cells. These results demonstrate that IL-12 can be used
      to alter the host immune response leading to induction of cytotoxic effector
      cells that inhibit the development and/or progressive growth of otherwise
      resistant B cell lymphomas in SJL/J mice.

PMID- 12007507
TI  - Pulmonary alveolar proteinosis as a terminal complication in myelodysplastic
      syndromes: a report of four cases detected on autopsy.
AB  - Secondary pulmonary alveolar proteinosis (PAP) is one of the complications of
      hematologic malignancy and immunosuppressive diseases. We encountered four cases
      of myelodysplastic syndrome (MDS) associated with PAP detected on autopsy. They
      consisted of two refractory anemia (RA) and two patients with refractory anemia
      with excess blasts in transformation (RAEBt) at the time of MDS diagnosis, but
      all of them developed leukemic phase and were resistant to chemotherapy at the
      time of pulmonary episodes. Of the four MDS patients, two also had pulmonary
      aspergillosis. Previously, 69 patients with PAP associated with hematologic
      disorders have been reported, but there have been only seven cases with MDS,
      including our four patients. Of the 69 reported cases of PAP in hematologic
      malignancies, 24/63 (38%) informative patients with infection had fungal
      infections of the lung; 2/7 (29%) MDS cases had fungal infection. We should,
      therefore, pay careful attention to this possibility in cases of MDS with lung
      complications, including PAP, especially in patients in the leukemic phase of
      MDS.

PMID- 12007508
TI  - Evidence for T-large granular lymphocyte-mediated neutropenia in Rituximab
      treated lymphoma patients: report of two cases.
AB  - We report two cases with B cell malignancies (case #1: refractory mantle cell
      lymphoma; case #2: lymphocyte predominant Hodgkin's disease (LPHD)) who developed
      neutropenia post-Rituximab therapy in a setting of significant infiltration of
      the peripheral blood (PB) and bone marrow (BM) by T cells with an immunophenotype
      of large granular lymphocytes. Possible pathogenetic mechanisms are discussed.

PMID- 12007509
TI  - A case of smouldering mastocytosis with peripheral blood eosinophilia and
      lymphadenopathy.
AB  - Systemic mastocytosis (SM) is a clonal hematologic disease showing abnormal
      growth and accumulation of mast cells (MC) in visceral organs with or without
      skin involvement. The clinical course in SM is variable. In fact, indolent and
      aggressive variants have been described. In addition, SM patients may acquire an
      associated hematologic clonal non-MC lineage disease (AHNMD). In some cases,
      hematologic parameters are indicative of slowly progressing SM although the
      clinical course remains indolent over years. These cases have been referred to as
      smouldering SM. We report on a smouldering patient presenting with typical skin
      lesions, hypercellular marrow with focal MC aggregates, persistent leukocytosis
      (20,000-30,000/microl) with eosinophilia (5-10%), marked lymphadenopathy, and
      splenomegaly. The C-KIT mutation Asp-816-Val confirmed the diagnosis of SM. The
      clinical picture remained stable during an observation period of 10 years without
      signs of progression to an AHNMD or a high grade MC disease. These data show that
      some patients with SM can remain in a clinically indolent smouldering state over
      years even when presenting with marked eosinophilia and lymphadenopathy.

PMID- 12007510
TI  - UK CLL Forum, London, 25th October 2001.

PMID- 12007511
TI  - Familial myeloid leukemias from the Swedish Family-Cancer Database.

PMID- 12007513
TI  - An investigation into the influence of boundary condition specification in finite
      difference methods on the behaviour of passive and active neuronal models.
AB  - Neuronal models provide a major aid to understanding the behaviour of individual
      neurons and networks of neurons. The solution of the model equations by finite
      difference methods is widespread because of the inherent simplicity of the
      technique. Error in the finite difference approach due to spatial and temporal
      discretisation is shown to be equivalent to a mis-specification of membrane
      current density. The effect of this mis-specification on the accuracy of the
      solution to the model equations is shown to depend on the structure of the model
      and its input, as well as the size of the discretisation intervals themselves.
      Through a theoretical analysis, illustrated by a number of examples on passive
      and active dendrites, this article demonstrates that the accuracy with which core
      current is implemented numerically at segment end-points in elementary models
      influences the behaviour of the numerical solution of these models, and
      consequently any physiological conclusions drawn from them.

PMID- 12007514
TI  - An analytical study of the physiology and pathology of the propagation of cardiac
      action potentials.
AB  - Many cardiac diseases are caused by the abnormal propagation of electrical waves.
      Previous experimental and modelling work is reviewed, then a detailed study of
      the mathematics of cardiac propagation is presented. Pathologies are examined in
      the context of the models by varying parameters in the models to mimic different
      pathological states. Ionic models of cells are simplified to form analytically
      tractable models of the propagation of electrical cardiac waves. The roles that
      sodium channel activation and inactivation play in determining the conduction
      velocity are studied in detail, and the roles of resting potential currents in
      conduction block are calculated. The effect of curvature on the conduction
      velocity is examined, and the conditions in which curvature leads to conduction
      block and fibrillation are discussed. Hyperkalaemia (important during ischaemia)
      is modelled, and the model correctly describes the bi-phasic relation between
      propagation velocity and extracellular potassium.

PMID- 12007516
TI  - The cellular basis of contraction in human detrusor smooth muscle from patients
      with stable and unstable bladders.
AB  - Studying the cellular physiology of human detrusor muscle obtained from patients
      with normally functioning bladders and comparing it with that of detrusor muscle
      from patients with unstable bladders may help identify potential targets for drug
      therapy in patients with abnormal bladder function. Considerable advances have
      been made in the understanding of the cellular processes that result in
      contraction and relaxation of detrusor smooth muscle, particularly in the role
      and modulation of calcium. Several changes in these cellular mechanisms that
      impair normal function have been observed in detrusor muscle from patients with
      unstable bladders. Whether these changes represent primary causes of bladder
      dysfunction or whether they are secondary to bladder dysfunction remains to be
      determined. Nevertheless, the identification of specific cellular lesions in
      bladder dysfunction presents a novel approach to identification of drug targets
      and potential treatment modalities.

PMID- 12007517
TI  - Central pathways controlling micturition and urinary continence.
AB  - The central control of micturition and urinary continence in cats and humans is
      organized in a similar manner. In cats, 4 areas in the brainstem and diencephalon
      are implicated in the control of micturition: (1) the pontine micturition center
      or Barrington area directly excites bladder motoneurons in the sacral cord during
      micturition; at the same time, it inhibits indirectly, via inhibitory gamma
      aminobutyric acidergic and glycinergic interneurons in the medial sacral cord,
      the external urethral sphincter motoneurons; (2) the pontine continence center
      activates the external urethral sphincter motoneurons during continence; (3) the
      midbrain periaqueductal gray receives bladder filling information; and (4) the
      hypothalamus, in the beginning of micturition. According to positron emission
      tomography studies, in humans, the same supraspinal regions are active during
      micturition. Furthermore, the human cingulate and prefrontal cortices are
      activated during both micturition and continence, indicating that these areas are
      important for the onset of micturition, but not for the reflex itself. The
      primary motor cortex of the pelvic floor is important for voluntary pelvic floor
      contraction, but it is not involved in normal urinary continence.

PMID- 12007518
TI  - Treatment of the overactive bladder: possible central nervous system drug
      targets.
AB  - The well-known side effects of antimuscarinic drugs have focused interest on
      other modalities of treatment of the overactive bladder. To effectively control
      bladder activity, identification of suitable targets for pharmacologic
      intervention is necessary. Such targets may be found in the central nervous
      system (CNS) or peripherally. Several CNS transmitters may modulate voiding, but
      few drugs with a defined CNS site of action have been developed for treatment of
      voiding disorders. Drugs affecting gamma-aminobutyric acid, opioid, serotonin,
      noradrenaline, dopamine, or glutamatergic receptors and mechanisms are known to
      influence micturition, and potentially such drugs could be developed for clinical
      use. However, a selective action on the lower urinary tract may be difficult to
      obtain.

PMID- 12007519
TI  - Beta3-adrenoceptors in human detrusor muscle.
AB  - The detrusor muscle contains beta-adrenoceptors (beta-AR), and 2 subtypes-beta1
      AR and beta2-AR-have been identified in most species. Although beta2-AR has an
      important role in muscle relaxation via activation of adenylate cyclase, evidence
      suggests that a third subtype, beta3-AR, which is implicated in metabolic
      functions of endogenous catecholamines, mediates relaxation of human detrusor
      muscle. There is a predominant expression of beta3-AR messenger RNA (mRNA) in
      human bladder tissue, with 97% of total beta-AR mRNA being represented by the
      beta3-AR subtype and only 1.5% and 1.4% by the beta1-AR and beta2-AR subtypes,
      respectively. Functionally, selective beta3-AR agonists relax human isolated
      detrusor, whereas selective beta1-AR/beta2-AR agonists do not. Isoproterenol
      induced relaxation is inhibited by selective beta3-AR antagonists but not by
      selective beta1-AR or beta2-AR antagonists. In animal models, beta3-AR agonists
      increase bladder capacity and have only weak cardiovascular side effects.
      Although this evidence points toward the clinical utility of beta3-AR agonists as
      therapy for overactive bladder, clinical trials of beta3-AR agonists identified
      in animal models as antiobesity agents indicate side effects of tremor and
      tachycardia. Development of compounds with high selectivity for the human beta3
      AR, identified by screening techniques using cell lines transfected with the
      human beta1-AR, beta2-AR, and beta3-AR genes, may mitigate such problems.
      Together with the preliminary finding that 49% (21 of 43) of patients with
      idiopathic detrusor instability have a tryptophan 64 arginine mutation of the
      beta3-AR gene, which may be a useful genetic marker, evidence points toward beta3
      AR being a therapeutic target for treatment of overactive bladder disorder.

PMID- 12007520
TI  - Influence of central serotonergic mechanisms on lower urinary tract function.
AB  - The effects of serotonergic drugs on the central nervous system control of the
      lower urinary tract have revealed possible approaches for the treatment of
      detrusor overactivity and urinary incontinence. Studies in animals of the
      distribution of serotonergic nerves and receptors and the changes in voiding
      function induced by serotonin (5-hydroxytryptamine [5-HT]) receptor agonists and
      antagonists, as well as 5-HT reuptake inhibitors, form a basis for the
      development of such treatments. In rats and cats, spinal reflex circuits involved
      in voiding function exhibit a dense serotonergic innervation, multiple 5-HT
      receptors, and sensitivity to various drugs that affect serotonergic
      transmission. Although there is some evidence in the rat for serotonergic
      facilitation of voiding, most experiments in rats and cats indicate that
      activation of the central serotonergic system by 5-HT reuptake inhibitors, as
      well as by 5-HT1A and 5-HT2 receptor agonists, depresses reflex bladder
      contractions and increases the bladder volume threshold for inducing micturition.
      These data indicate that activation of the central serotonergic system can
      suppress voiding by enhancing efferent control of the urethral outlet and
      inhibiting the parasympathetic excitatory input to the urinary bladder. The 5-HT
      receptors and reuptake mechanisms, therefore, represent targets for the
      development of new treatments of detrusor overactivity and urinary incontinence.

PMID- 12007521
TI  - Bladder afferents and their role in the overactive bladder.
AB  - The role of afferent innervation of the bladder in the pathophysiology of urinary
      incontinence has become the focus of intense interest. In normal health, the
      afferent pathway is mediated largely by Adelta-fibers, which ultimately send
      information about the state of bladder fullness to the pontine micturition center
      via the periaqueductal gray matter. However, after spinal disruption, a different
      type of afferent pathway emerges, mediated by capsaicin-sensitive C-fibers that
      drive a spinal segmental reflex pathway, causing neurogenic detrusor
      overactivity. The common sources of afferent information for either pathway are
      likely to be afferents from the urothelium, lamina propria, and afferents that
      originate in the bladder wall. Ultrastructural investigations of the constituent
      neural elements of these structures contribute to our knowledge of their role in
      both health and disease and help provide a rational approach to treatment
      strategies. Evidence of the involvement of capsaicin-sensitive C-fibers in the
      spinal reflex pathway has been supported by the successful treatment of patients
      with neurogenic incontinence with intravesical capsaicin or its ultrapotent
      nonpungent analog, resiniferatoxin. On the other hand, capsaicin has not been
      shown to be clearly effective in treatment of overactive bladder caused by
      detrusor overactivity or suprapontine pathology without the emergent C-fiber
      mediated reflex. It is hoped that continued investigation of neurotoxins that
      have the potential to act on afferent innervation will lead to other treatment
      strategies for bladder disorders and other disorders involving afferent
      dysfunction.

PMID- 12007522
TI  - Bladder activation: afferent mechanisms.
AB  - The major function of the lower urinary tract is to store and periodically
      evacuate urine from the bladder. This requires coordination of the smooth muscles
      of the bladder and urethra, and of the striated muscles of the outflow region and
      pelvic floor by a complex neural control system. Lumbosacral afferent fibers
      (pelvic afferents), but also afferents in the hypogastric and pudendal nerves,
      are of major importance for the regulation of the mechanisms for continence and
      micturition. In the bladder, afferent nerves have been identified suburothelially
      as well as in the detrusor muscle. Suburothelially, they form a plexus that lies
      immediately beneath the epithelial lining. This plexus is particularly dense in
      the bladder neck and the trigone. The most important afferents for the
      micturition process are myelinated Adelta-fibers and unmyelinated C-fibers.
      Immunocytochemical and tracing studies have revealed that numerous peptides,
      including substance P, calcitonin gene-related peptide, vasoactive intestinal
      polypeptide, enkephalins, and cholecystokinin are localized either alone, or in
      combination, in afferent pathways of the bladder and urethra. The receptors on
      these nerves include: vanilloid receptors, purinoceptors, tachykinin, and
      prostanoid receptors. Extracellular adenosine triphosphate (ATP) has been found
      to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and
      it has been proposed that in the bladder, distention causes release of ATP from
      the urothelium. ATP, in turn, can activate P2X3 receptors on suburothelial
      afferent nerve terminals to evoke a neural discharge. However, it is most likely
      that a cascade of inhibitory and stimulatory transmitters/mediators, as well as
      ATP, are involved in the transduction mechanisms underlying the activation of
      afferent fibers during bladder filling.

PMID- 12007523
TI  - Vanilloid receptor and detrusor instability.
AB  - Very recently, a membrane receptor (vanilloid receptor type 1 [VR-1]) sensitive
      to capsaicin or resiniferatoxin (RTX) was identified in small- and medium-sized
      dorsal root ganglion neurons that give rise to most unmyelinated sensory fibers.
      After vanilloid binding to VR-1, these neurons remain transiently desensitized;
      that is, less reactive to natural stimuli. It is this effect of vanilloid
      substances that is being investigated for its potential therapeutic utility. In
      the urinary bladder, VR-1-expressing fibers are extremely abundant in the mucosa
      and in the muscular layer. In the latter, VR-1 fibers are intimately apposed to
      smooth muscle cells. The demonstration, several years ago, that these fibers were
      involved in detrusor hyperreflexia of spinal origin and in bladder pain
      processing, justified the clinical application of intravesical capsaicin or RTX
      in humans with these bladder diseases. More recently, the experimental and
      clinical evidence that the same type of bladder sensory fibers were also involved
      in detrusor instability made a strong case for intravesical RTX assay in patients
      with idiopathic detrusor instability.

PMID- 12007524
TI  - Targeting afferent hyperexcitability for therapy of the painful bladder syndrome.
AB  - The involvement of C-fiber afferent pathways in urinary frequency and pain
      associated with painful bladder syndrome raises the possibility of multiple
      targets for the treatment of this disease. Using an in vivo measurement of
      bladder activity as well as whole-cell patch clamp recording techniques to
      examine the properties of bladder afferent neurons in animal models of chronic
      cystitis, we have documented that tetrodotoxin-resistant sodium channels encoded
      by the Na(v) 1.8 (PN3/SNS) gene and nitric oxide acting via a cyclic guanosine
      monophosphate (cGMP)-dependent mechanism are important in modulating bladder pain
      responses. Thus, suppression of C-fiber afferent nerve activity by blocking
      specific sodium channels, elevating nitric oxide levels, or activating cGMP
      dependent pathways might represent novel strategies for the treatment of symptoms
      in patients with painful bladder syndrome. Another treatment strategy is
      suppression of release or activity of proinflammatory agents that can cause
      normally unexcitable C-fiber afferents to become hyperactive or hyperexcitable.
      This approach to management of bladder pain was tested in patients with painful
      bladder syndrome by examining the effectiveness of the antiallergic agent
      suplatast tosilate (IPD-1151T), which suppresses urinary frequency in a rat model
      of cystitis. IPD-1151T is an immunoregulator that suppresses cytokine production
      in T-helper 2 cells and inhibits immunoglobulin E antibody formation and antigen
      induced histamine release from mast cells. Preliminary data from an open-label
      clinical trial showed that 16 of 23 (70%) patients responded to treatment with
      IPD-1151T (300 mg/day orally for 12 months). The finding that expression of
      platelet-derived endothelial cell growth factor, which can activate mast cells,
      was lower in the bladder of responders than nonresponders indicates that bladder
      levels of platelet-derived endothelial cell growth factor may be a useful marker
      for this disease.

PMID- 12007525
TI  - Targets for therapy of the painful bladder.
AB  - Interstitial cystitis is an elusive disorder. Without a defining etiology and
      distinctive pathophysiology, diagnosis is made on an exclusionary basis.
      Treatment strategies for the disease vary, as do estimates of its prevalence.
      Nevertheless, advances are being made in understanding this disease. Basic
      research is helping to define rational treatment approaches for interstitial
      cystitis, and new therapies based on the findings of such research are being
      developed. This article reviews the theories of the etiology of interstitial
      cystitis and reviews the evidence for clinical effectiveness of various
      treatments.

PMID- 12007527
TI  - Thyroid hormones in the pathogenesis and treatment of obesity.
AB  - Thyroid hormones (TH) are potent modulators of adaptive thermogenesis and can
      potentially contribute to development of obesity. The decrease of T(3) in
      association with reduction of calorie intake is centrally regulated via decreases
      in leptin and melanocortin concentrations and peripherally via a decrease in
      deiodinase activity, all aimed at protein and energy sparing. The use of TH in
      the treatment of obesity is hardly justified except in cases of elevated
      thyrotropin (TSH) with low/normal T(3) and T(4) and/or a low T(3) or T'(3)/T(4)
      or a high TSH/T(3) ratio. TH treatment with small doses of T(3) can also be
      exceptionally applied in obese patients resistant to dietary therapy who are
      taking beta-adrenergic blockers or with obesity developed after cessation of
      cigarette smoking and with hyperlipidemia and a concomitant high
      thryrotropin/T(3) ratio. Supplementation with Se(2+) and Zn(2+) may be tried
      along with more severe calorie restriction to prevent decline of T(3).

PMID- 12007528
TI  - beta(3)-Adrenoceptor agonists: potential, pitfalls and progress.
AB  - beta(3)-Adrenoceptor agonists are very effective thermogenic anti-obesity and
      insulin-sensitising agents in rodents. Their main sites of action are white and
      brown adipose tissue, and muscle. beta(3)-Adrenoceptor mRNA levels are lower in
      human than in rodent adipose tissue, and adult humans have little brown adipose
      tissue. Nevertheless, beta(3)-adrenoceptors are expressed in human white as well
      as brown adipose tissue and in skeletal muscle, and they play a role in the
      regulation of energy balance and glucose homeostasis. It is difficult to identify
      beta(3)-adrenoceptor agonist drugs because the pharmacology of both beta(3)- and
      beta(1)-adrenoceptors can vary; near absolute selectivity is needed to avoid
      beta(1/2)-adrenoceptor-mediated side effects and selective agonists tend to have
      poor oral bioavailability. All weight loss is lipid and lean may actually
      increase, so reducing weight loss relative to energy loss. beta(3)-adrenoceptor
      agonists have a more rapid insulin-sensitising than anti-obesity effect, possibly
      because stimulation of lipid oxidation rapidly lowers intracellular long-chain
      fatty acyl CoA and diacylglycerol levels. This may deactivate those protein
      kinase C isoenzymes that inhibit insulin signalling.

PMID- 12007529
TI  - Orlistat: its current status as an anti-obesity drug.
AB  - Orlistat is a non-centrally acting anti-obesity agent that acts locally in the
      gastrointestinal tract to inhibit lipase, an enzyme that is crucial for the
      digestion of long-chain triglycerides. At the recommended dose of 120 mg three
      times daily, orlistat inhibits dietary fat absorption by about 30%. Over a 1-year
      period, obese patients taking orlistat in combination with a hypocaloric diet
      show a reduction of 2-5 kg over the weight decrease with placebo. When continued
      for a second year in combination with a weight maintenance diet, orlistat reduces
      weight regain compared to placebo-treated patients. Orlistat in combination with
      dietary intervention is also associated with beneficial effects on cardiovascular
      risk factors including total and low-density lipoprotein cholesterol, blood
      pressure and plasma glucose. It is not known if orlistat has any impact on
      clinical outcomes such as myocardial infarction, stroke and sudden death.
      Orlistat has not been compared with other anti-obesity agents.

PMID- 12007530
TI  - The discovery and status of sibutramine as an anti-obesity drug.
AB  - Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the
      management of obesity in conjunction with a reduced calorie diet. Though
      sibutramine was originally evaluated for possible use as an antidepressant, its
      research development was eventually redirected to evaluate it as an anorexiant.
      The pharmacological mechanisms by which sibutramine exerts its weight loss effect
      are likely due to a combination of reduced appetite, feelings of satiety, and
      possibly the induction of thermogenesis. Its efficacy for inducing an initial
      weight-loss and the subsequent maintenance of the weight-loss is well proven in
      short- and long-term clinical trials of up to 2 years duration. In general,
      sibutramine has been well tolerated. Increases in blood pressure and heart rate
      are possible adverse effects that require regular monitoring. Sibutramine is one
      of the few established and well-proven agents for obesity available for use today
      and should be considered effective in the management of patients requiring
      pharmacotherapy as part of the multi-modal approach to weight-loss.

PMID- 12007531
TI  - Leptin and the treatment of obesity: its current status.
AB  - Leptin, the protein product of the ob gene, is primarily an adipocyte-secreted
      hormone, whose functional significance is rapidly expanding. Although early
      research efforts were focused on defining leptin's role in reversing obesity in
      rodents, there is now substantial evidence indicating that its influence extends
      to several hypothalamic-pituitary-endocrine axes, including gonadal, adrenal,
      thyroid, growth hormone, and pancreatic islets. A role for leptin in
      hematopoiesis, angiogenesis, immune function, osteogenesis, and wound healing has
      also been documented. The results of recent clinical trials with recombinant
      human leptin indicated that its effectiveness in restoring energy balance and
      correcting obesity-related endocrinopathies in genetically obese rodent models
      extended only partially to the management of human obesity. New efforts in drug
      development have focused on leptin-related synthetic peptide agonists as
      potential anti-obesity pharmacophores.

PMID- 12007532
TI  - The role of melanocortins in body weight regulation: opportunities for the
      treatment of obesity.
AB  - Five G-protein-coupled melanocortin receptors (MC(1)-MC(5)) are expressed in
      mammalian tissues. The melanocortin receptors support diverse physiological
      functions, including the regulation of hair color, adrenal function, energy
      homeostasis, feed efficiency, sebaceous gland lipid production and immune and
      sexual function. The melanocortins (adrenocorticotropic hormone (ACTH), alpha
      melanocyte-stimulating hormone (alpha-MSH), beta-MSH and gamma-MSH) are agonist
      peptide ligands for the melanocortin receptors and these peptides are processed
      from the pre-prohormone proopiomelanocortin (POMC). Peptide antagonists for the
      melanocortin MC(1), MC(3) and MC(4) receptors include agouti-related protein
      (AgRP) and agouti. Diverse lines of evidence, including genetic and
      pharmacological data obtained in rodents and humans, support a role for the
      melanocortin MC(3) and MC(4) receptors in the regulation of energy homeostasis.
      Recent advances in the development of potent and selective peptide and non
      peptide melanocortin receptor ligands are anticipated to help unravel the roles
      for the melanocortin receptors in humans and to accelerate the clinical use of
      small molecule melanocortin mimetics.

PMID- 12007533
TI  - Ups and downs for neuropeptides in body weight homeostasis: pharmacological
      potential of cocaine amphetamine regulated transcript and pre-proglucagon-derived
      peptides.
AB  - Although most humans experience an underlying upwards drift of the body-weight
      set-point, body weight appears tightly regulated throughout life. The present
      review describes the structural basis of the adipostat and hypothesise, which
      components may constitute available targets for pharmacotherapy of excess body
      weight. Hypothalamic neurones constitute the major components of the body weight
      homeostasis maintaining device. Together with neurones of the nucleus of the
      solitary tract, neurones of the hypothalamic arcuate nucleus constitute the
      sensory components of the adipostat. The arcuate nucleus neurones respond to
      circulating levels of leptin and insulin, both of which reflect the levels of
      energy stored as triacylglycerol in adipocytes. The arcuate nucleus projects
      heavily to the hypothalamic paraventricular nucleus. Neurones of the hypothalamic
      paraventricular nucleus are hypothesised to constitute, at least partly, the
      adipostat motor pattern generator, which upon stimulation activates either net
      anabolic or catabolic physiological responses. The overall sensitivity of the
      adipostat is influenced by gain setting neurones hypothesised to be located in
      the dorsomedial hypothalamic nucleus and lateral hypothalamic area. Cocaine
      amphetamine regulated transcript (CART) peptides and pre-proglucagon derived
      peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are
      catabolic neurotransmitters synthesised in neurones of the arcuate nucleus and
      the nucleus of the solitary tract, respectively. The present review summarises
      the available evidence that both families of peptides constitute endogenous
      transmitters mediating satiety and touch upon potential pharmacological
      exploitation of this knowledge.

PMID- 12007534
TI  - Neuropeptide Y receptors as targets for anti-obesity drug development:
      perspective and current status.
AB  - Neuropeptide Y is a widely distributed neuropeptide that elicits a plethora of
      physiological effects via interaction with six different receptors (Y(1)-y(6)).
      Recent attention has focused on the role of neuropeptide Y in the regulation of
      energy homeostasis. Neuropeptide Y stimulates food intake, inhibits energy
      expenditure, increases body weight and increases anabolic hormone levels by
      activating the neuropeptide Y Y(1) and Y(5) receptors in the hypothalamus. Based
      on these findings, several neuropeptide Y Y(1) and Y(5) receptor antagonists have
      been developed recently as potential anti-obesity agents. In addition, mice
      lacking neuropeptide Y, the neuropeptide Y Y(1) receptor or the neuropeptide Y
      Y(5) receptor have been generated. The data obtained to date with these newly
      developed tools suggests that neuropeptide Y receptor antagonists, particularly
      neuropeptide Y Y(1) receptor antagonists, may be useful anti-obesity agents.
      However, the redundancy of the neurochemical systems regulating energy
      homeostasis may limit the effect of ablating a single pathway. In addition,
      patients in whom the starvation response is activated, such as formerly obese
      patients who have lost weight or patients with complete or partial leptin
      deficiency, may be the best candidates for treatment with a neuropeptide Y
      receptor antagonist.

PMID- 12007535
TI  - The corticotropin-releasing factor family of peptides and CRF receptors: their
      roles in the regulation of energy balance.
AB  - The corticotropin-releasing factor (CRF) system could play a significant role in
      the regulation of energy balance. This system, which includes CRF, CRF-related
      peptides and CRF receptors, is part of a huge network of cells connected to
      central and peripheral pathways modulating energy metabolism. CRF and CRF-related
      peptides, which elicit their effects through G-protein-coupled receptors known in
      mammals as CRF(1) receptor and CRF(2) receptor, are capable of strong anorectic
      and thermogenic effects. Also supporting a role for the CRF system in the
      regulation of energy balance are findings demonstrating alterations in this
      system in obese and food-deprived animals that concur to facilitate energy
      deposition. In recent years, great progress has been made in understanding the
      specific physiological roles of the CRF system. In that respect, the discovery of
      urocortins II and III, two endogenous ligands of the CRF(2) receptor, and the
      development of selective and long-acting antagonists for the CRF receptors, have
      led to a better comprehension of the role of the CRF system in the regulation of
      energy balance. Although there are still important unresolved issues in the field
      of CRF research, the progress made recently warrants investigations aimed at
      evaluating the CRF system as a potential target for anti-obesity drugs.

PMID- 12007536
TI  - Orexins and the treatment of obesity.
AB  - Orexin-A and -B are two peptides derived by proteolytic cleavage from a 130-amino
      acid precursor, prepro-orexin, which were recently isolated from the rat
      hypothalamus. Orexin-A is fully conserved across mammalian species, whilst rat
      and human orexin-B differ by two amino acids. These peptides bind to two Gq
      coupled receptors, termed orexin-1 and orexin-2. The receptors are 64% homologous
      and highly conserved across species. Orexin-A is equipotent at orexin-1 and
      orexin-2 receptors, whilst orexin-B displays moderate (approximately 10 fold)
      selectivity for orexin-2 receptors. The distribution and pharmacology of the
      orexin peptides and their receptors indicate that they play a role in various
      regulatory systems including energy homeostasis and the regulation of feeding,
      the evidence for which is reviewed here.

PMID- 12007537
TI  - ACRP30, a new hormone controlling fat and glucose metabolism.
AB  - Adipocyte complement-related protein of 30 kDa (ACRP30) is a secreted serum
      protein expressed exclusively in differentiated adipocytes. Recent studies have
      indicated that its expression and serum levels are reduced in humans and animals
      with obesity and insulin resistance. Metabolic studies have demonstrated a role
      for ACRP30 in the regulation of glucose and lipid homeostasis. This review will
      describe the current literature on the biochemistry of ACRP30 and its
      physiological functions. We will also discuss issues that are relevant to the
      directions of future research.

PMID- 12007538
TI  - Peroxisome proliferator activated receptors and obesity.
AB  - The peroxisome proliferator activated receptors (PPARs) are a group of ligand
      activated transcription factors that govern numerous biological processes,
      including energy metabolism, cell proliferation, and inflammation. Three
      different PPAR isotypes can be distinguished: alpha, beta and gamma. PPARalpha is
      mainly present in liver where it has an important role in the regulation of
      nutrient metabolism, including fatty acid oxidation, gluconeogenesis, and amino
      acid metabolism. It mediates the effects of fibrates, which are drugs used in the
      treatment of hyperlipidemia, on DNA transcription. Little is still known about
      PPARbeta. The PPARgamma isotype is mainly expressed in adipose tissue where it
      stimulates adipogenesis and lipogenesis. It is the target of a group of anti
      diabetic drugs called thiazolidinediones. As PPARs have a very important role in
      the regulation of energy metabolism, and as their activity can be modulated by
      drugs, there is an increasing interest in the potential connection between PPARs
      and obesity. In this article, the diverse pieces of evidence that have linked
      PPARs with obesity are reviewed. Furthermore, the association between PPARs and
      type 2 diabetes is discussed.

PMID- 12007539
TI  - Neuroendocrine and peripheral activities of ghrelin: implications in metabolism
      and obesity.
AB  - Ghrelin, a 28-amino acid acylated peptide predominantly produced by the stomach,
      displays strong growth hormone (GH)-releasing activity mediated by the
      hypothalamus-pituitary GH secretagogue (GHS)-receptors specific for synthetic
      GHS. The discovery of ghrelin definitely changes our understanding of GH
      regulation but it is also already clear that ghrelin is much more than simply a
      natural GHS. Ghrelin acts also on other central and peripheral receptors and
      shows other actions including stimulation of lactotroph and corticotroph
      secretion, orexia, influence on gastro-entero-pancreatic functions, metabolic,
      cardiovascular and anti-proliferative effects. GHS were born more than 20 years
      ago as synthetic molecules suggesting the option that GH deficiency could be
      treated by orally active GHS as an alternative to recombinant human GH (rhGH). Up
      to now, this has not been the case and also their usefulness as anabolic anti
      aging intervention restoring GH/insulin-like growth factor-I axis in somatopause
      is still unclear. We are now confronted with the theoretical possibility that GHS
      analogues could become candidate drugs for treatment of pathophysiological
      conditions in internal medicine totally unrelated to disorders of GH secretion.
      Particularly, GHS receptor agonists or antagonists acting on appetite could
      represent new drug intervention in eating disorders.

PMID- 12007540
TI  - Galanin/GALP and galanin receptors: role in central control of feeding, body
      weight/obesity and reproduction?
AB  - Scientific and commercial pharmacological interest in the role of galanin and
      galanin receptors in the regulation of food intake, energy balance, and obesity
      has waned recently, following initial enthusiasm during the 1980-1990s. It has
      been replaced by efforts to understand the role of newly discovered peptide
      systems such as the hypocretin/orexins, melanocortins and cocaine- and
      amphetamine-regulated transcript (CART) and their relationship to the important
      hormones, leptin and insulin. Thus, while numerous studies have revealed the
      ability of galanin to stimulate food intake via actions at sites within the
      hypothalamus, and shown reliable changes in hypothalamic galanin synthesis in
      response to food ingestion; findings including the lack of a 'body
      weight/obesity' phenotype in galanin transgenic mouse strains and a lack of
      agonists/antagonists for galanin receptor subtypes have probably served to reduce
      enthusiasm. However, as more is learnt about the general and galanin-related
      neurochemistry of brain pathways involved in feeding, metabolism and body weight
      control, the potential importance of galanin systems is again in focus. Studies
      of the newly discovered galanin family peptide, 'galanin-like peptide' (GALP),
      highlight the likely role of galanin peptides and receptors in the physiological
      coupling of body weight, adiposity and reproductive function. GALP is produced by
      a discrete population of neurons within the basomedial arcuate nucleus (and
      median eminence) that send projections to the anterior paraventricular nucleus
      and that make close contacts with leutinizing hormone-releasing hormone (LHRH)
      neurons in basal forebrain. Furthermore, GALP neurons express leptin receptors
      and respond to leptin treatment by increasing their expression of GALP mRNA.
      Centrally administered GALP activates LHRH-immunoreactive neurons and increases
      plasma LH levels. These findings suggest a direct stimulatory action of
      endogenous GALP on gonadotropin secretion via actions within the
      hypothalamus/basal forebrain, with leptin actions linking this system to body
      adipose levels.

PMID- 12007541
TI  - Glucagon-like peptide 1 as a regulator of food intake and body weight:
      therapeutic perspectives.
AB  - After ingestion of carbohydrate- and fat-rich meals, the incretin hormone
      glucagon-like peptide 1 (GLP-1) is secreted from the L-cells in the distal put
      into the circulation. Its major physiological effect lies in a strongly glucose
      dependent stimulation of insulin secretion from pancreatic B-cells. Furthermore,
      GLP-1 suppresses glucagon secretion, stimulates B-cell neogenesis as well as
      proinsulin biosynthesis and inhibits gastric emptying and acid secretion.
      Recently, GLP-1 could be shown to reduce caloric intake and to enhance satiety,
      most likely via specific receptors within the central nervous system, resulting
      in reduced weight gain in experimental animals. In nondiabetic and Type 2
      diabetic human subjects, exogenous GLP-1 reduces hunger, caloric intake and body
      weight. Therefore, in addition to its well-characterized antidiabetogenic effect,
      the anorectic effect may offer GLP-1 a potential in the pharmacotherapy of
      obesity. It is still unknown whether the GLP-1 effect on caloric intake is
      sustained after long-term treatment. Furthermore, the exact mechanisms by which
      the peptide exerts its biological effects have not yet been clarified. Due to the
      rapid degradation of native GLP-1, its therapeutic application is limited by the
      short half-life. Therefore, suitable modes of administration are needed in order
      to reach stable plasma concentrations. The present review aims to describe the
      role of GLP-1 in the central regulation of feeding and to discuss its possible
      application in the pharmacotherapy of obesity.

PMID- 12007542
TI  - Bombesin and its family of peptides: prospects for the treatment of obesity.
AB  - Bombesin, its family of bombesin-like peptides, and many other peptides/hormones
      modulate biological and behavioral functions in animals. Among the wide variety
      of functions influenced by bombesin/bombesin-like peptides, the most prominent
      may be their role in feeding-related behavior. Over many years, intensive
      psychopharmacological studies have addressed the mechanisms by which these
      peptides induce feeding suppression, and the results suggest the applicability of
      bombesin/bombesin-like peptides for the treatment of eating disorders and/or
      obesity in humans. Recent studies using gene-knockout mice also shed new light on
      the relationship between bombesin/bombesin-like peptides and feeding behavior. In
      addition, genetic analyses of the possible links between bombesin/bombesin-like
      peptides/receptors and human obesity have also been undertaken. Here, we briefly
      review the literature pertaining to the relationship between bombesin/bombesin
      like peptides and feeding behavior-with particular attention to human subjects
      and discuss the pharmacotherapeutic potential of bombesin/bombesin-like peptides
      with regard to obesity.

PMID- 12007543
TI  - Post-therapeutic response and therapeutic "style": re-formulating the "placebo
      effect".

PMID- 12007544
TI  - What are the main methodological problems in the estimation of placebo effects?
AB  - Researchers disagree whether placebo effects are clinically important. The
      controversy is partly due to conceptual and methodological problems. The
      objective of this paper is to analyze the main methodological problems in the
      estimation of placebo effects. Variations in the meaning of the concept of
      placebo effect are described, and the main methodological problems are analyzed.
      The notion of placebo effect has at least two main meanings: effect of placebo
      intervention, and effect of patient-provider interaction. When the terms are
      defined pragmatically, effects of placebo can be estimated as the difference
      between placebo and no-treatment in randomized trials. The effect of patient
      provider interaction can similarly be assessed by comparing manipulation of the
      patient-provider interaction with no manipulation. In both cases bias due to lack
      of double-blinding is a potential problem.

PMID- 12007545
TI  - Exploratory causal modeling in epidemiology: are all factors created equal?
AB  - The purpose of this study was to demonstrate the consequences of analyzing
      sequentially caused relationships with models assuming equally proximate
      causation. Monte Carlo simulations of data with well defined causations were
      performed. The logistic modeling approach was strongly misleading if a distant
      causal factor was treated as a factor being equally distant to the outcome as a
      proximal causal factor. In contrast, simple pathway analysis was able to
      correctly identify the true causation. In causal pathways, the relative risk of
      an intermediate cause with respect to the outcome needs to have a certain
      magnitude for the effect of the distant variable to be passed on. The results
      further show that the true relative risk of the distant variable is not dependent
      on its baseline prevalence. In contrast, the prevalence of the intermediate
      variable must be small enough to carry the influence of the distant variable
      through the causal chain. Practical epidemiologic exploration of etiological
      factors is presently dominated by stepwise multiple regression. This type of
      exploration is not model free but is often intuitively based on the structural
      assumption of equal proximity of all potential factors to the outcome. Equal
      proximity, however, is not likely in many etiologies, especially not if the
      causal factors under consideration are of different quality, like psychological
      and biological factors. In cases of causal pathways with some factors more
      distant and others more proximal to the outcome, the former tend to be dismissed
      by equal proximity modeling. Upstream exploration of more distant etiological
      factors is hindered by endemic stepwise multiple regression modeling, treating
      all variables as being equal in proximity to the outcome.

PMID- 12007546
TI  - C-reactive protein and myocardial infarction.
AB  - C-reactive protein (CRP) has been shown to predict cardiovascular disease.
      Whether predictions differ across risk factor strata and for short and long-term
      follow-up has not been clearly examined. The purpose of this report is to assess
      the relation between CRP and the development of myocardial infarction (MI) over a
      20-year period in men in the Honolulu Heart Program. Subjects were aged 48 to 70
      years and free of prevalent disease at the time when CRP levels were measured and
      follow-up began. Using a case-control design, 369 cases of MI were compared with
      1,348 control subjects. After risk factor adjustment, the odds of an MI rose with
      increasing levels of CRP as early as 5 years into follow-up (P = 0.009).
      Associations appeared to persist beyond this time, but after 15 years, effects
      became modest. Adverse effects of an elevated CRP level were observed in middle
      aged men (< or =55 years), in men without hypertension or diabetes, and in those
      who were nonsmokers (P < 0.05). Although positive effects were also observed in
      those who were hypertensive and smoking at the time of CRP measurement, findings
      suggest that in clinically healthy men, atherosclerosis could have origins more
      closely linked with inflammation than with other processes.

PMID- 12007547
TI  - The accuracy of self-reported fractures in older people.
AB  - Self-report is often used in large-scale studies. Therefore, it is important to
      determine the accuracy of self-report. In the Blue Mountains Eye Study, a
      population-based study of 3,654 older, community-dwelling Australians, subjects
      were asked about fracture history at the 5-year follow-up interview. All reported
      non-rib and vertebral fractures were radiologically confirmed. Hospital radiology
      records were searched for fracture records of people who reported no fractures in
      the 5-year period. Of 2,326 subjects who came to the interview, 272 subjects
      reported 318 fractures sustained since 1990. Overall, 34.6% of fracture reports
      could not be confirmed, mainly due to no record of treatment. Among self-reported
      fractures, false positive rates were 10.7% for all fractures and 4.8% for hip,
      2.2% for wrist, 19.4% for ankle, and 6.6% for shoulder fractures. Sensitivity and
      specificity of fracture reports was high, with the lowest sensitivity for
      shoulder fractures (82.4%). Self-report of major osteoporotic fractures is
      reasonably accurate but may be improved by obtaining more details about
      treatment.

PMID- 12007548
TI  - Implantable cardioverter defibrillator implantation rates in the Olmsted County,
      Minnesota, population: 1989-1999.
AB  - Although the efficacy of implantable cardioverter defibrillators (ICDs) has been
      demonstrated in randomized clinical trials, implantation and survival rates have
      not been reported for a defined population. We performed a retrospective cohort
      analysis of Olmsted County, Minnesota residents (n = 70) who received their first
      ICD between 1 January 1989 and 31 December 1999. The ICD implantation rate
      increased from approximately 2.5/100,000 (95% confidence interval [CI], 0.9-4.1)
      in the first 4 years to 11.5/100,000 (95% CI, 6.7-16.2) in the last 2 years.
      Twenty-three patients (33%) received an appropriate ICD shock during the
      observation period. Based on these data, ICDs are estimated to reduce total
      mortality rates in this population by 0.3%. We conclude that, in patients drawn
      from a community setting with AHA/ACC class I indications for ICD implantation,
      implantation of ICDs appears to be highly efficacious in aborting potentially
      fatal events.

PMID- 12007549
TI  - Predictors of nursing home admission and/or death in incident Alzheimer's disease
      and other dementia cases compared to controls: a population-based study.
AB  - This research elucidates the risk of institutional care and/or death of patients
      with Alzheimer's disease (AD) or other dementia (OD) compared with noncases.
      Community dwelling incident cases of AD (n = 240) or OD (n = 208) and age-matched
      noncases (n = 363) living in an enumerated population were included. The adjusted
      hazard ratio (HR) of being admitted to a nursing home compared with controls was
      5.44 (95% confidence interval, CI: 3.68,8.05) for AD cases and 5.08 (95% CI:
      3.38, 7.63) for OD cases. The adjusted RR of death compared to controls was 1.90
      (95% CI: 1.36, 2.65) for AD cases and 2.27 (95% CI: 1.62, 3.18) for OD cases.
      This is the only population-based study in the U.S. documenting that AD/OD
      increases the risk of death independent of comorbid conditions. AD/OD patients
      have more comorbidities and are at greater risk of entering a nursing home than
      to die during the follow-up, compared with those without these diagnoses.

PMID- 12007550
TI  - Trends in fatal coronary heart disease among people aged 25-74 years in Oita
      City, Japan, from 1987-1998.
AB  - Serum cholesterol has been increasing in recent years in Japan. There is concern
      that risk of coronary heart disease (CHD) may be increasing too, but there is
      little information on validated fatal CHD trends in the Japanese population. We
      identified 1,056 deaths from heart disease and other deaths possibly hiding CHD
      from death certificates of residents aged 25-74 years in Oita City, Japan in 1987
      1988, 1992-1993, and 1997-1998 (mean population, 273,000 in 1997-1998). We
      validated 994 of them by medical record review and physician interviews,
      classifying them into definite fatal acute myocardial infarction (AMI) and
      possible fatal AMI or CHD death based on Monitoring Trends and Determinants in
      Cardiovascular Disease project's criteria. Sudden death was defined to estimate
      the number of CHD sudden deaths. In men, age-adjusted mortality rates due to
      validated fatal CHD remained quite stable over 10 years (25.3 per 100,000 [95%
      CI, 15.0-35.5] in 1987-1988 to 24.2 per 100,000 [95% CI, 16.1-32.3] in 1997
      1998). When 50% or all sudden deaths were included as fatal CHD, the rates for
      men tended to decline. This was due to decreasing out-of-hospital deaths in
      connection with a declining CHD death rate among men aged 65-74 years, whereas in
      hospital CHD deaths were level. In women, the rate of validated fatal CHD was
      highest in 1992-1993, but the 1997-1998 rate was similar to the 1987-1988 rate.
      We did not find that fatal CHD rates increased in Oita men and women from 1987
      1998. Rather, out-of-hospital fatal CHD tended to decline in Oita men.

PMID- 12007551
TI  - Methodologic issues in a population-based health survey of Gulf War veterans.
AB  - This report describes the principal methods used in the development, conduct, and
      analysis of the research study "Health Assessment of Persian Gulf War Veterans
      from Iowa" (Iowa Gulf War Study). The methods presented include an outline of the
      organizational structure, study timeline, hypotheses, outcome definitions, and
      study design. Adhering to a strict timeline, the study protocol and instruments
      were developed, and a stratified sample of 3,695 military personnel (76%
      participation) was located and surveyed by structured telephone interview. The
      study tracked personnel from all service branches residing nationally and
      internationally, including those discharged from service. This study required
      development and implementation of methods appropriate to analysis of data
      collected in a complex sampling framework and methodological procedures to ensure
      scientific rigor in a highly public and politicized environment. Statistical
      analyses were conducted on a priori health outcomes and required development of
      methods to compute Cochran-Mantel-Haenszel adjusted rate differences. This
      environment facilitated rapid implementation, critique by scientific and public
      advisors, a high participation rate, and rapid publication.

PMID- 12007552
TI  - Comparison of the responsiveness of lupus disease activity measures to changes in
      systemic lupus erythematosus activity relevant to patients and physicians.
AB  - Both the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI) are valid and reliable measures of
      disease activity in systemic lupus erythematosus (SLE). However, more study of
      their responsiveness is needed. The purpose of this study was to compare the
      responsiveness of SLAM-R and SLEDAI to disease activity changes relevant to
      physicians and patients. Patients were evaluated monthly for up to 12 months. At
      each visit, the physician completed SLAM-R and SLEDAI. Patients and physicians
      assessed whether relevant improvement or worsening of disease activity had
      occurred since the previous visit. Based on repeated measurements, effect size
      (ES), standardized response mean (SRM), and control-standardized response mean
      (CSRM) were calculated for each response category, with bootstrap-based 95%
      confidence intervals (CIs). Seventy-six patients contributed 471 score changes.
      For physicians' responses, the CSRMs for SLAM-R and SLEDAI were -0.47 versus 
      0.42 for improvement, 0.04 versus 0.003 for no change, and 0.65 versus 0.66 for
      deterioration. For patients, the CSRMs for SLAM-R and SLEDAI were -0.31 versus 
      0.18 for improvement, -0.08 versus 0.06 for no change, and 0.48 versus 0.05 for
      deterioration. Only for SLAM-R did the 95% CIs exclude zero when improvement or
      deterioration were detected. Similar results were found for ES and SRM. Both SLAM
      R and SLEDAI are responsive to changes in SLE disease activity important to
      physicians. Only SLAM-R is responsive to changes important to patients. These
      differences may result from the inclusion of subjective SLE manifestations in
      SLAM-R.

PMID- 12007553
TI  - Screening for pressure ulcer risk in an acute care hospital: development of a
      brief bedside scale.
AB  - To derive a brief bedside pressure ulcer prediction tool for patients admitted to
      acute care hospitals, we conducted a prospective study of first pressure ulcer
      incidence among 1,190 consecutive patients hospitalized in selected wards of a
      Swiss teaching hospital. Baseline predictors included patient age and items from
      the Norton and Braden ulcer prediction scales. During follow-up, 170 patients
      developed new pressure ulcers. The predictive ability of baseline assessments
      decayed over time. Occurrence of first pressure ulcer in the 5 days after
      admission (129 events) was best predicted by patient age (5 levels), mobility (3
      levels), mental status (3 levels), and friction/shear (3 levels). The Fragmment
      score (sum of friction, age, mobility, mental status) was linearly related to
      pressure ulcer risk, and its area under the receiver operating characteristic
      curve (0.80) was higher than for the Norton (0.74; P = 0.006) and Braden (0.74; P
      = 0.004) scores. This brief pressure ulcer prediction scale performed well in an
      acute care setting. Use of this scale may facilitate the implementation of
      pressure ulcer prevention interventions.

PMID- 12007554
TI  - Comparability of epidemiological information between self- and interviewer
      administered questionnaires.
AB  - The aim of the present study was to determine the extent to which respondents
      provided the same answers to a health-related lifestyle questionnaire in self-
      and interviewer-administered forms. A total of 234 subjects completed a 110-item
      questionnaire in both interviewer and self-administered forms. Modes of
      administration were separated by a 2-week interval. The order was determined by
      random allocation. The presence and the extent of the tendency to give socially
      acceptable responses were evaluated using percentage of bias calculated as the
      ratio of the difference in proportion of positive responses or the mean between
      interviews and questionnaires and those in questionnaires. All percentages of
      bias were in the positive direction, ranging from 1.4% (physical exercise) to
      26.1% (general life stress). The average percentage of bias was higher in women
      than in men and were stronger for younger respondents. The age differences
      between interviewer and respondent were inversely and most strongly related to
      percentage of bias. Self- and interviewer-administered questionnaires yield very
      similar results in discriminating between subjects, but the interviewer
      administered questionnaire showed systematically more desirable responses to
      questions related to lifestyle factors. The differences in characteristics
      between interviewer and respondent may be important determinants of the socially
      desirability bias in the interview.

PMID- 12007555
TI  - Self-assessed global quality of life: a comparison between African-American and
      white older patients with arthritis.
AB  - Quality of life (QOL) perceptions influence patient decisions and preferences for
      care and, more importantly, physicians may render recommendations based on their
      impressions of the patient's QOL. QOL is perceived differently by different
      ethnic groups. This may have implications for understanding ethnic disparities in
      medical procedure utilization such as joint replacement for osteoarthritis. In a
      study of 596 elderly male patients with moderate to severe symptomatic knee/hip
      osteoarthritis, we examined how African-American and white patients rate their
      overall QOL. We adjusted their responses for important demographic, clinical, and
      psychosocial potential confounders. African-American (44%) and white (56%)
      patients in this study were comparable, except that African-Americans reported
      lower socioeconomic status compared with whites. After adjusting for all other
      study covariates, African-American ethnicity (B= -0.121, P = 0.004) was
      negatively correlated with overall QOL ratings. How ethnic variations in
      perceptions of QOL impact observed ethnic disparity in the utilization of joint
      replacement therapy needs further investigation.

PMID- 12007556
TI  - Statistical characteristics of area under the receiver operating characteristic
      curve for a simple prognostic model using traditional and bootstrapped
      approaches.
AB  - Prognostic models are increasingly common in the biomedical literature. These
      models are frequently evaluated with respect to their ability to discriminate
      between those with and without an outcome. The area under the receiver-operating
      curve (AROC) is often used to assess discrimination. In this study, we introduce
      a bootstrap method, and, using Monte Carlo simulation, we compare three different
      bootstrap approaches with four commonly used methods in their ability to
      accurately estimate 95% confidence intervals (CIs) around the AROC for a simple
      prognostic model. We also evaluated the power of a bootstrap method and the
      commonly used trapezoid rule to compare different prognostic models. We show that
      several good methods exist for calculating 95% CIs of AROC, but the maximum
      likelihood estimation method should not be used with small sample sizes. We
      further show that for our simple prognostic model a bootstrap z-statistic
      approach is preferred over the trapezoidal method when comparing the AROCs of two
      related models.

PMID- 12007557
TI  - Calculating the "number needed to be exposed" with adjustment for confounding
      variables in epidemiological studies.
AB  - The number needed to treat (NNT) is a popular summary statistic to describe the
      absolute effect of a new treatment compared with a standard treatment or control
      concerning the risk of an adverse event. The NNT concept can be applied whenever
      the risk of an adverse event is compared between two groups; for the comparison
      of exposed with unexposed subjects in epidemiological studies, we propose the
      term "number needed to be exposed" (NNE). Whereas in randomized clinical trials
      NNT can be calculated on the basis of a simple 2 x 2 table, in epidemiological
      studies methods to adjust for confounders are required in most applications. We
      derive a method based upon multiple logistic regression analysis to perform point
      and interval estimation of NNE with adjustment for confounding variables. The
      adjusted NNE can be calculated from the adjusted odds ratio (OR) and the
      unexposed event rate (UER) estimated by means of an appropriate multiple logistic
      regression model. As UER is dependent on the confounders, the adjusted NNEs also
      vary with the values of the confounding variables. Two methods are proposed to
      take the dependence of NNE on the values of the confounders into account. The
      adjusted number needed to be exposed can be a useful complement to the commonly
      presented results in epidemiological studies, such as ORs and attributable risks.

PMID- 12007558
TI  - Quick estimation of threshold "number needed to treat".

PMID- 12007560
TI  - Leptin, gut, and food intake.
AB  - Hyperphagia (overeating) is often associated with energy over-storage and
      obesity, which may lead to a myriad of serious health problems, including heart
      disease, hypertension, and type 2 diabetes. Thus, understanding the complex
      pathological mechanisms underlying hyperphagia and obesity has an important
      clinical significance. Leptin, or ob protein, is a key element in the long-term
      regulation of food intake and body weight homeostasis. It circulates in the blood
      at levels correlated with body fat mass. Leptin binds to specific receptors in
      the hypothalamus to mediate events that regulate feeding behavior. In light of
      new evidence, the initial view that leptin is an adipocyte-derived signal, which
      acts centrally to decrease body weight, has been modified. It has been shown that
      leptin may also have specific functions in the gastrointestinal tract, suggesting
      that feeding and energy homeostasis is regulated by both central and peripheral
      signals. Evidence supports the view that leptin integrates short-term, meal
      related signals from the gut into long-term regulation of energy balance. In
      addition, the gastric leptin level is altered by the nutritional state and the
      administration of cholecystokinin. This commentary aims to review the evidence of
      the role of leptin as a peripherally acting signal in the gut in the regulation
      of nutrient intake, adiposity, and body weight. Based on currently available
      data, some potential future studies are suggested.

PMID- 12007561
TI  - Homologous recombinational repair vis-a-vis chlorambucil resistance in chronic
      lymphocytic leukemia.
AB  - The objective of this study was to further define the role of homologous
      recombinational repair (HRR) in resistance to the nitrogen mustards in B-cell
      chronic lymphocytic leukemia (B-CLL). We have demonstrated previously that
      increased chlorambucil (CLB)-induced HsRad51 nuclear foci formation correlated
      with a CLB-resistant phenotype in B-CLL lymphocytes. In this report, we measured
      the protein levels of HsRad51 and Xrcc3 (an HsRad51 paralog) and correlated them
      with the in vitro CLB cytotoxicity (LD(50)) in lymphocytes from seventeen B-CLL
      patients. Both HsRad51 (r=0.75, P=0.0005) and Xrcc3 (r=0.52, P=0.03) protein
      levels correlated with the in vitro CLB LD(50). In addition, multiple linear
      regression analysis showed a significant correlation between Xrcc3 and Rad51
      protein levels versus the CLB LD(50) (r=0.78, P=0.0014), suggesting that both
      proteins influence CLB cytotoxicity. Moreover, since HsRad51 expression varies in
      cell lines during the cell cycle, we determined proliferating cell nuclear
      antigen (PCNA) protein levels to assess possible differences in cell cycle
      progression. There was no correlation between PCNA protein levels and the CLB
      LD(50) (r=0.042, P=0.87) or with HsRad51/Xrcc3 protein levels. Our data suggest
      that HsRad51 and Xrcc3 protein expression may be predictive of the response in B
      CLL patients to treatment with nitrogen mustards.

PMID- 12007562
TI  - Purification and characterization of a phospholipase A2 isoenzyme isolated from
      Lachesis muta snake venom.
AB  - A new phospholipase A2 (PLA2) isoenzyme was isolated from Lachesis muta crude
      venom, and was named LM-PLA2-II. This enzyme was purified by gel filtration on a
      Sephacryl S-200 HR column followed by reverse-phase chromatography on a C2/C18
      column. LM-PLA2-II consists of a single polypeptide chain with an apparent
      molecular mass of 18 kDa and an isoelectric point at pH 5.4. The amino terminal
      sequence of the enzyme revealed a high degree of homology with other PLA2s from
      several sources. LM-PLA2-II has a high indirect hemolytic activity and a potent
      inhibitory effect on platelet aggregation induced by ADP and collagen. It also
      produces a significant paw edema reaction in rats. The edematous response in rats
      was abolished by pretreatment with either indomethacin or dexamethasone,
      suggesting the involvement of cyclo-oxygenase. Pretreatment of LM-PLA2-II with p
      bromophenacyl bromide abolished all of these actions, clearly indicating that the
      biological activities, including the edematogenic effect, are dependent entirely
      on its enzymatic activity.

PMID- 12007563
TI  - Structural refinement of inhibitors of urea-based soluble epoxide hydrolases.
AB  - The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic,
      linoleic, and other fatty acid epoxides, endogenous chemical mediators that play
      an important role in blood pressure regulation and inflammation. 1,3
      Disubstituted ureas, carbamates, and amides are new potent and stable inhibitors
      of sEH. However, the poor solubility of the lead compounds limits their use.
      Inhibitor structure-activity relationships were investigated to better define the
      structural requirements for inhibition and to identify points in the molecular
      topography that could accept polar groups without diminishing inhibition potency.
      Results indicate that lipophilicity is an important factor controlling inhibitor
      potency. Polar groups could be incorporated into one of the alkyl groups without
      loss of activity if they were placed at a sufficient distance from the urea
      function. The resulting compounds had a 2-fold higher water solubility. These
      findings will facilitate the rational design and optimization of sEH inhibitors
      with better physical properties.

PMID- 12007564
TI  - Expression of p53-family members and associated target molecules in breast cancer
      cell lines in response to vincristine treatment.
AB  - As the antimitotic agent vincristine (VCR) has been reported to induce a weak p53
      response in some studies, we hypothesised that p73 and p63, the recently
      described p53 homologues, may replace p53 in triggering apoptosis or cell cycle
      arrest effectors in VCR-treated cell lines. To address this issue, we measured
      p53, p73 and p63 mRNA and protein levels in two VCR-treated breast cancer cell
      lines, one p53-proficient (MCF7) and the other p53-deficient (MDA-MB157). We
      found an increase of p53 mRNA and protein levels in VCR-treated MCF7 cells,
      while, as expected, no p53 protein was detected in VCR-treated MDA-MB157 cells.
      Surprisingly, the p73 mRNA and protein expression levels decreased in both cell
      lines during VCR treatment, whereas p63 protein levels remained unchanged. In
      both cell lines, up-regulations of the canonical p53-target genes, such as p21
      and GADD45, were consistently observed. We conclude that, in response to VCR
      treatment: (1) p53 is markedly induced in MCF7 cells, with the same extent than
      after DNA damaging drugs treatments; and (2) p63 is not involved, while p73
      expression is down-regulated regardless of the p53 status of the cell lines. Our
      results therefore suggest the involvement of a fourth member of the p53 gene
      family, or the use of another pathway able to trigger canonical p53-target genes
      in response to VCR in p53-deficient cells.

PMID- 12007565
TI  - A GAL4-based yeast three-hybrid system for the identification of small molecule
      target protein interactions.
AB  - We report the development of a yeast strain designed for assaying compound
      protein interactions through activation of reporter gene expression. Activation
      of lacZ expression, driven by the GAL4 promoter, has been demonstrated for
      precedented compound-protein interactions between FK506 and FK506 binding protein
      12 (FKBP12) and also between methotrexate (MTX) and dihydrofolate reductase
      (DHFR). Reporter gene expression was completely abrogated in a competitive manner
      by the presence of excess FK506 or MTX, respectively. In addition, a strain
      expressing a mutated DHFR clone with decreased binding affinity for MTX was not
      capable of activating reporter gene expression. While strain sensitivity is
      compound-dependent, the minimum compound concentration necessary to drive
      reporter gene expression was 20 nM for the FK506-FKBP12 interaction. The utility
      of this strain as a tool for identifying unknown compound-binding proteins has
      been demonstrated by screening a mouse cDNA library for clones that encode
      proteins capable of binding MTX. Four library clones of mouse DHFR were
      identified after screening 5 x 10(6) clones. The screen background was low and
      false positives were easily identified, making this yeast system particularly
      amenable for use in a screening context for novel compound-protein interactions.

PMID- 12007566
TI  - Modifying rates of reductive elimination of leaving groups from indolequinone
      prodrugs: a key factor in controlling hypoxia-selective drug release.
AB  - 3-(4-Methylcoumarin-7-yloxy)methylindole-4,7-diones were synthesised as model
      prodrugs in order to investigate the correlation between rates of reductive
      elimination from the (indolyl-3-yl)methyl position with reductive metabolism by
      hypoxic tumor cells and NADPH: cytochrome P450. Rates of elimination of the
      chromophore/fluorophore (7-hydroxy-4-methylcoumarin) following one-electron
      reduction of indolequinones to their semiquinone radicals (Q*-) was measured by
      pulse radiolysis utilising spectrophotometric and fluorometric detection.
      Incorporation of a thienyl or methyl substituent at the (indol-3-yl)CHR-position
      (where R=thienyl or methyl adjacent to the phenolic ether linking bond)
      significantly shortened the half-life of reductive elimination from 87 to 6 and 2
      ms, respectively. Elimination from the methyl substituted analogue can thus
      compete effectively with the reaction of the semiquinone radical with oxygen at
      levels typically present in tumours (half-life approximately 1.8 ms at 0.5% O2).
      Chemical kinetic predictions were confirmed by metabolism in breast tumour MCF-7
      cells between 0-2.1% O2. Rates of reductive release of the fluorophore from the
      non-fluorescent parent indolequinones (R=H, Me, thienyl) were similar under
      anoxia ( approximately 1.7 nmol coumarinmin(-1)mg protein(-1)) reflecting the
      similarity in one-electron reduction potential. Whereas coumarin release from the
      indolequinone (R=H) was completely inhibited above 0.5% O2, the enhanced rate of
      reductive elimination when R=thienyl or Me increased the metabolic rate of
      release to approximately 0.35 and 0.7 nmol coumarinmin(-1)mg protein(-1),
      respectively at 0.5% O2; complete inhibition occurring by 2.1% O2. Similar
      'oxygen profiles' of release were observed with NADPH: cytochrome P450 reductase.
      In conclusion, it is possible to modify rates of reductive elimination from
      indolequinones to control the release of drugs over a range of tumour hypoxia.

PMID- 12007567
TI  - Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of
      caspases during honokiol-induced apoptosis in human squamous lung cancer CH27
      cells.
AB  - Honokiol is a phenolic compound purified from Magnolia officinalis, which induced
      the apoptotic cell death in several types of human cancer cells. In the present
      study, the molecular mechanism of honokiol-mediated apoptotic process was
      examined in human squamous lung cancer CH27 cells. Here, we found that honokiol
      induced apoptotic cell death was accompanied by upregulation of Bad and
      downregulation of Bcl-XL, while honokiol had no effect on the levels of Bcl-2,
      Bcl-XS, Bag-1, Bax and Bak proteins. Moreover, honokiol treatment caused the
      release of mitochondrial cytochrome c to cytosol and sequential activation of
      caspases. Proteolytic activation of caspase-3 and cleavage of PARP, an in vivo
      substrate for caspase-3, were observed in honokiol-treated CH27 cells.
      Furthermore, treatment with caspase inhibitors z-DEVD-fmk and z-VAD-fmk markedly
      blocked honokiol-induced apoptosis. These results demonstrated that modulation of
      Bcl-XL and Bad proteins, release of mitochondrial cytochrome c and activation of
      caspase-3, participated in honokiol-triggered apoptotic process in human squamous
      lung cancer CH27 cells.

PMID- 12007568
TI  - Intercalation of imidazoacridinones to DNA and its relevance to cytotoxic and
      antitumor activity.
AB  - Imidazoacridinones (IA) are a class of antitumor agents which includes C-1311, an
      interesting drug in clinical trials. This study investigated the mechanism of IA
      binding to DNA for a series of 13 analogs that differ in their cytotoxic potency.
      Using C-1311 as a model compound, crystallographic, spectroscopic and biochemical
      techniques were employed to characterize drug-DNA interactions. X-ray
      crystallographic analysis revealed a planar structure of imidazoacridinone core
      that is capable of intercalative DNA binding. Accordingly, C-1311 binding to DNA
      followed 'classical' pattern observed for intercalation, as proved by the DNA
      topoisomerase I-unwinding experiments, with relatively weak binding affinity
      (K(i)=1.2 x 10(5)M(-1)), and the binding site size of 2.4 bp. Other IA also bound
      to DNA with the binding affinity in the range of 10(5)M(-1) and binding site size
      of 2-3 bp, suggesting a prevalence of the intercalative mechanism, similar to C
      1311. Considerable DNA binding affinity was displayed by all the highly cytotoxic
      derivatives. However, none of the analyzed drug-DNA binding parameters was
      significantly correlated with IA biological activities such as cell growth, DNA
      and RNA synthesis inhibition, or tumor growth inhibition, which suggests that the
      IA ability to non-covalently bind to DNA is not crucial for their biological
      activity. These results show that the ability to intercalate into DNA is a
      prominent attribute of IA, although factors other than intercalative binding seem
      to be required for the biological activities of IA drugs.

PMID- 12007569
TI  - The influence of charge clustering on the anti-HIV-1 activity and in vivo
      distribution of negatively charged albumins.
AB  - The substitution of human serum albumin with negatively charged molecules, such
      as succinic acid (Suc-HSA) or aconitic acid (Aco-HSA), resulted in proteins with
      potent anti-HIV activities, by binding to viral gp120 (V3 loop). The aim of the
      present study was to investigate whether the distribution of negative charges on
      the albumin backbone influences the anti-HIV activity. Therefore, we prepared
      albumins with clusters of negatively charged groups by coupling of heparin. The
      effects of this substitution on anti-HIV activity, in vivo distribution and the
      protein structure as compared to random succinylation were assessed. In vitro
      studies indicated that HSA-modified with heparin 6 or 13 kD displayed anti-HIV
      activity (IC50=660 and 37 nM, respectively) and exhibited affinity for gp120-V3
      loop, although the activity was lower than that of Suc-HSA. Combined
      derivatization of HSA with heparin 13 kD and aconitic acid groups resulted in
      significantly increased inhibitory actions (IC50=2.8 nM). Structural analysis
      showed that modification of HSA with heparin did not lead to extensive unfolding
      of the protein, meaning that these modified proteins were still globular in
      structure. In contrast, succinylation of HSA resulted in a highly randomly coiled
      conformation. Dynamic light scattering experiments revealed that, at neutral pH,
      the heparin fragments attached to the protein were wrapped around the molecule
      rather than sticking out into the solution. In conclusion, coupling of sufficient
      clustered negative charges, by coupling of Hep-fragments, on HSA resulted in a
      clear anti-HIV activity of the protein. Yet, random distribution of anionic
      groups in the albumin seemed more optimal for in vitro anti-HIV activity. The
      higher plasma and lymphatic concentrations of Hep-HSA compared to Suc-HSA seemed
      more favorable for an anti-HIV activity in vivo.

PMID- 12007570
TI  - Analysis of C-terminally substituted tachykinin-like peptide agonists by means of
      aequorin-based luminescent assays for human and insect neurokinin receptors.
AB  - Aequorin-based assays for stable fly, Stomoxys calcitrans, (STKR) and human
      (neurokinin receptor 1 (NK1), neurokinin receptor 2 (NK2)) neurokinin-like
      receptors were employed to investigate the impact of a C-terminal amino acid
      exchange in synthetic vertebrate ('FXGLMa') and invertebrate ('FX1GX2Ra')
      tachykinin-like peptides. C-terminally (Arg to Met) substituted analogs of the
      insect tachykinin-related peptide, Lom-TK I, displayed increased agonistic
      potencies in luminescent assays for human NK1 and NK2 receptors, whereas they
      showed reduced potencies in the STKR-assay. The opposite effects were observed
      when C-terminally (Met to Arg) substituted analogs of substance P were analysed.
      These substance P analogs proved to be very potent STKR-agonists, being more
      potent than Lom-TK I. On the other hand, Lom-TK-LMa, was shown to be a very
      potent NK1-agonist and was suggested to have more substance-P-mimetic than
      neurokinin-A-mimetic properties. NK1 and NK2 receptor agonists appeared to be
      more sensitive to changes at the penultimate amino acid position than STKR
      agonists. This is also reflected in the sequence conservation that is observed in
      the naturally occurring tachykinin subgroups ('FXGLMa' vs. 'FX1GX2Ra'). The
      differential Arg-Met preference appears to be a major coevolutionary change
      between insect and human peptide-receptor couples. With regard to the peptide
      agonists, this change can theoretically be based on a single point mutation.

PMID- 12007571
TI  - Tissue-specific regulation of canine intestinal and hepatic phenol and morphine
      UDP-glucuronosyltransferases by beta-naphthoflavone in comparison with humans.
AB  - UDP-glucuronosyltransferases (UGTs) are regulated in a species- and tissue
      dependent manner by endogenous and environmental factors. The present study was
      undertaken to further our knowledge about regulation of UGTs in dogs, a species
      widely used in preclinical safety evaluation. beta-Naphthoflavone (BNF) was
      selected as a known aryl hydrocarbon receptor agonist and antioxidant-type
      inducer. The latter group of inducers is intensively investigated as dietary
      chemoprotectants against colon cancer. Dog UGTs were investigated in comparison
      with related human UGTs by examples, (i) expression of dog UGT1A6, the first
      sequenced dog phenol UGT, and (ii) morphine UGT activities, responsible for
      intestinal and hepatic first-pass metabolism of morphine. The following results
      were obtained: (i) dog UGT1A6 was found to be constitutively expressed in liver
      and marginally increased by BNF treatment. Expression was low in small intestine
      but ca. 6-fold higher in colon than for example in jejunum. Conjugation of 4
      methylumbelliferone, one of the substrates of dog UGT1A6, was also enhanced 7
      fold in colonic compared to jejunal microsomes. (ii) Compared to the
      corresponding human tissues, canine 3-O- and 6-O-morphine UGT activities were
      found to be >10-fold higher in dog liver and ca. 10-fold lower in small
      intestinal microsomes. Small intestinal morphine and 4-hydroxybiphenyl UGT
      activities appeared to be moderately (2- to 3-fold) induced by oral treatment
      with BNF. (iii) In contrast to dogs, morphine UGT activities were found to be
      similar in homogenates from human enterocytes and liver. The results suggest
      marked differences in tissue-specific regulation of canine vs. human hepatic and
      intestinal phenol or morphine UGTs.

PMID- 12007572
TI  - Recognition forces involved in mitochondrial binding to a low-affinity
      trimetazidine binding site related to anti-ischemic activity.
AB  - A number of heterogeneous drugs previously shown to bind to trimetazidine (TMZ)
      binding sites on mitochondria and to inhibit mitochondrial swelling (Morin et
      al., Br J Pharmacol 1998;123:1385-94) were investigated here for their
      physicochemical properties. The molecular parameters measured were the partition
      coefficients of the neutral and monocationic forms in the n-octanol/water and
      dichloroethane/water systems, their distribution coefficients at pH 7.4 in these
      two solvent systems, as well as their distribution coefficients at pH 7.4 in a
      phosphatidylcholine (PhC) liposomes/water system (log D(lip)(7.4)). Most of these
      properties were not correlated with affinity to mitochondria or inhibition of
      mitochondrial swelling. In contrast, log D(lip)(7.4) showed a modest correlation
      with binding to the low-affinity site (r(2)=0.52) and a better correlation with
      anti-swelling activity (r(2)=0.69), itself well correlated with binding to the
      low-affinity sites (r(2)=0.83). Thus, these sites have recognition properties
      much like those of membranes, as they depend on lipophilicity-hydrophobicity
      (core binding) and ionic bonds (surface interactions).

PMID- 12007573
TI  - Reversal of cisplatin resistance in human ovarian cancer cell lines by a c-jun
      antisense oligodeoxynucleotide (ISIS 10582): evidence for the role of
      transcription factor overexpression in determining resistant phenotype.
AB  - Human ovarian cancer cell lines derived from A2780 by stepwise exposure to
      increasing cisplatin concentrations show progressive resistance to cisplatin.
      Previous studies have shown increased cellular glutathione and elevated steady
      state expression of gamma-glutamylcysteine synthetase (gamma-GCS) and of the
      transcription factor c-Jun, all in proportion to the level of resistance in the
      resistant cells. We hypothesized that c-Jun was an important locus of control of
      the detoxicating enzymes mediating resistance, and that resistance reversal would
      be achieved by specific inhibition of this mechanism. A2780 (sensitive) and C30
      (resistant) cells were treated with a 20-mer c-jun phosphorothioate antisense
      oligodeoxynucleotide (ISIS 10582, 1 microM), and a decrease in steady-state c-jun
      mRNA was demonstrated in the resistant cells. The expression of gamma-GCS mRNA
      was down-regulated and the cellular level of glutathione was decreased in C30
      cells. No change in gamma-GCS expression occurred in A2780 cells. Using the
      microtetrazolium (MTT) cytotoxicity assay, we determined that the c-jun antisense
      decreased the IC50 value for cisplatin in C30 cells from 18.2 to 3.7 microM, and
      had a substantially smaller effect in A2780 cells. To determine if c-jun
      overexpression alone could confer resistance to the sensitive cell line, we
      transiently transfected A2780 cells with a c-jun expression vector. The
      transfected cells exhibited a 10.7-fold elevation of glutathione (GSH) content, a
      9.2-fold increase in c-Jun protein content, and a 2-fold increase in the IC50 for
      cisplatin. These data suggest that altered regulation of transcription factor
      expression contributes to the acquired resistance phenotype in these ovarian
      cancer cells, and provide a novel potential target for therapeutic intervention.

PMID- 12007574
TI  - Basal levels and patterns of anticancer drug-induced activation of nuclear factor
      kappaB (NF-kappaB), and its attenuation by tamoxifen, dexamethasone, and curcumin
      in carcinoma cells.
AB  - Nuclear factor-kappaB (NF-kappaB) has been implicated in the development of drug
      resistance in cancer cells. We systematically examined the baseline levels of NF
      kappaB activity of representative carcinoma cell lines, and the change of NF
      kappaB activity in response to a challenge with four major anticancer drugs
      (doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel). We found that the basal
      level of NF-kappaB activity was heterogeneous and roughly correlated with drug
      resistance. When challenged with various drugs, all the cell lines examined
      responded with a transient activation of NF-kappaB which then declined to basal
      level despite variation in the concentration of the agent and the timing of the
      treatment. In contrast to tumor necrosis factor-alpha (TNF-alpha), which
      activates NF-kappaB in minutes, NF-kappaB activation induced by anticancer drugs
      usually occurred more than 1hr after stimulation. A gradual increase of total NF
      kappaB and its nuclear translocation, and cytoplasmic translocation of nuclear
      IkappaBalpha and its degradation were involved in this process. In particular,
      when cells were pretreated with common biologic modulators such as tamoxifen,
      dexamethasone, and curcumin, the doxorubicin-induced NF-kappaB activation was
      attenuated significantly. This inhibition may play a role in sensitizing cancer
      cells to chemotherapeutic drugs. This study has demonstrated that activation of
      NF-kappaB is a general cellular response to anticancer drugs, and the mechanism
      of activation appears to be distinct from that induced by TNF-alpha. These
      observations may have implications for improving the efficacy of systemic
      chemotherapy for cancer patients.

PMID- 12007575
TI  - Role of the C-terminus and the long cytoplasmic loop in reduced folate carrier
      expression and function.
AB  - The reduced folate carrier (RFC1), a member of the major facilitative
      superfamily, generates uphill transport of folates into cells through an exchange
      mechanism with intracellular organic anions. RFC1 has twelve transmembrane
      domains with N- and C-termini, and the long loop connecting the 6th and 7th
      transmembrane domains, directed to the cytoplasm. To elucidate the role of the C
      terminus and the long cytoplasmic loop in carrier function, mutants with deletion
      of the entire C-terminus or with progressive deletions of the loop region were
      constructed and stably transfected into the murine MTX(r)A cell line, which lacks
      functional RFC1. While expression of the C-terminus-deleted RFC1 protein could
      not be detected in the cell lysate, the RFC1 mutant lacking 57 of 66 amino acid
      residues of the long cytoplasmic loop appeared to be inserted into the
      cytoplasmic membrane but was not functional. In cell lines in which 17 or 31
      amino acids were deleted from the carboxyl half of the loop, there was partial
      preservation of methotrexate, 5-formyltetrahydrofolate, and 5
      methyltetrahydrofolate transport. The loss of 5-formyltetrahydrofolate transport
      activity in the delta31 and delta17 mutants was due primarily to a decrease in
      substrate binding to the carrier. Mutants with partially truncated internal loops
      demonstrated an anion responsiveness similar to that of wild-type RFC1,
      indicating that this region of the carrier does not contain a site(s) that plays
      a role in anion exchange. This is the first study to describe the important role
      of the long cytoplasmic loop in substrate binding and the crucial role of the C
      terminus in maintaining stability of RFC1.

PMID- 12007576
TI  - Antioxidant properties of Thonningianin A, isolated from the African medicinal
      herb, Thonningia sanguinea.
AB  - The antioxidant properties of Thonningianin A (Th A), an ellagitannin, isolated
      from the methanolic extract of the African medicinal herb, Thonningia sanguinea
      were studied using the NADPH and Fe2+/ascorbate-induced lipid peroxidation (LPO),
      electron spin resonance spectrometer and the deoxyribose assay. Th A at 10 microM
      inhibited both the NADPH and Fe2+/ascorbate-induced LPO in rat liver microsomes
      by 60% without inhibitory effects on cytochrome P450 activity. Th A was similar
      to the synthetic antioxidant, tannic acid, as an inhibitor of both the NADPH and
      Fe2+/ascorbate-induced LPO but potent than gallic acid, vitamin C and vitamin E.
      While Th A poorly scavenged the hydroxyl radical generated by the Fenton reaction
      it dose-dependently scavenged 1,1-diphenyl-2-picrylhydrazyl, superoxide anion and
      peroxyl radicals with IC50 of 7.5, 10 and 30 microM, respectively. Furthermore,
      Th A showed inhibitory effects on the activity of xanthine oxidase with an IC50
      of 30 microM. In the deoxyribose assay both T. sanguinea and its methanolic
      component Th A showed only site-specific (Fe3+ + H2O2) but not non-site-specific
      (Fe3+ + EDTA + H2O2) hydroxyl radical scavenging suggesting chelating ability for
      iron ions. Spectroscopic studies showed that Th A enhanced absorbance in the
      visible region in the presence of Fe2+ ions. These results indicate that the
      antioxidant properties of Th A involve radical scavenging, anti-superoxide
      formation and metal chelation.

PMID- 12007577
TI  - Glutamate-cysteine ligase modifier subunit: mouse Gclm gene structure and
      regulation by agents that cause oxidative stress.
AB  - Glutamate-cysteine ligase is a heterodimer comprising a modifier (GCLM) and a
      catalytic (GCLC) subunit. In mouse Hepa-1c1c7 hepatoma cell cultures, we found
      that tert-butylhydroquinone (tBHQ; 50 microM) induces the GCLM and GCLC mRNAs
      approximately 10- and approximately 2-fold, respectively, and that these
      increases primarily reflect de novo transcription. We determined that the mouse
      Gclm gene has seven exons, spanning 22.3 kb; all exons, intron-exon junctions,
      and 4.7 kb of 5'-flanking region were sequenced. By RNase protection analysis, we
      identified two major and several minor transcription start-site clusters over a
      300-bp region. The Gclm 5'-flanking region is GC-rich and lacks a canonical TATA
      box. Transient and stable transfection studies, using luciferase reporter
      constructs containing incremental Gclm 5'-flanking deletions (4.7-0.5 kb), showed
      high basal activity but only modest ( approximately 2-fold) inducibility by tBHQ.
      The only candidate motif for oxidative stress regulation (in the 4.7-kb region we
      sequenced) is a putative inverted electrophile response element (EPRE) 9 bp
      upstream from the 5'-most transcription start-site. Site-directed mutagenesis of
      this -9 EPRE demonstrated minimal (30-40%) decreases in tBHQ induction and no
      effect on basal activity-suggesting that this EPRE might be necessary but not
      sufficient. The nuclear erythroid factor-2 (NEF2)-related factor-2 (NRF2) is
      known to transactivate via EPRE motifs. In the presence of co-transfected NRF
      cDNA expression vector, however, no increase in Gclm promoter activity was
      observed. Thus, the endogenous Gclm gene shows robust transcriptional activation
      by tBHQ in the intact Hepa-1 cell, but reporter constructs containing up to 4.7
      kb of promoter (having only the one EPRE at -9) demonstrate a disappointing
      response, indicating that the major tBHQ-responsive regulatory element of the
      mouse Gclm gene must exist either further 5'- or 3'-ward of the 4.7-kb region
      studied.

PMID- 12007578
TI  - HOE 402 lowers serum cholesterol levels by reducing VLDL-lipid production, and
      not by induction of the LDL receptor, and reduces atherosclerosis in wild-type
      and LDL receptor-deficient mice.
AB  - Previous rodent studies suggested that the potent hypolipidemic agent 4-amino-2
      (4,4-dimethyl-2-oxo-1-imidazolidinyl)pyrimidine-5-N-(trifluoromethyl-phenyl)
      carboxamide monohydrochloride (HOE 402) is an inducer of the LDL receptor (LDLR).
      Using wild-type and heterozygous and homozygous LDLR-deficient (LDLR+/0 and
      LDLR0/0) mice, fed a low or high cholesterol diet, we investigated whether HOE
      402 specifically induces the LDLR and whether other pathways are affected. Upon
      treatment with 0.05% (w/w) HOE 402, the serum cholesterol levels of wild-type,
      LDLR+/0 and LDLR0/0 mice, were maximally reduced by 53, 56, and 73%, respectively
      (P<0.05), by reducing levels in very low density-lipoprotein (VLDL), intermediate
      density-lipoprotein (IDL), and low density-lipoprotein (LDL) cholesterol, whereas
      high density-lipoprotein (HDL) cholesterol levels were increased. The
      observations that HOE 402 exhibited no effect on in vivo clearance of 125I
      labeled LDL in wild-type mice, and clearly reduced serum cholesterol levels in
      LDLR0/0 mice, indicate that the LDLR is not the main target for the compound. In
      wild-type mice, production of VLDL-TG, and cholesterol were reduced by more than
      50% by HOE 402 (P<0.05), whereas VLDL apolipoprotein B (ApoB) secretion was
      unaffected, indicating that HOE 402 treatment changes the size, rather than the
      number of the secreted VLDL particles. The reduced VLDL production was
      accompanied by a 22% decreased hepatic cholesterol ester concentration (P<0.05).
      Additionally, HOE 402 treatment strongly reduced the aortic content of
      atherosclerotic lesions by 90 and 72% in LDLR+/0 and LDLR0/0 mice, respectively
      (P<0.01). In conclusion, HOE 402 is a potent cholesterol-lowering compound, which
      inhibits VLDL production, and consequently attenuates atherosclerosis
      development.

PMID- 12007579
TI  - Characterisation of cyclic nucleotide phosphodiesterase isoforms in the media
      layer of the main pulmonary artery.
AB  - Cyclic nucleotides are involved in the control of pulmonary vascular tone. In the
      present study, we measured the cyclic nucleotide specific phosphodiesterase (PDE)
      activity in the media of bovine isolated main pulmonary artery (MPA). Total cAMP-
      and cGMP-PDE activities were measured in microsomal and cytosolic fractions. Both
      cyclic nucleotides were hydrolysed in these subcellular fractions at consistently
      higher rate in the cytosolic than in the microsomal fraction. Using different
      classes of PDE modulator, at least four PDE isoforms (PDE1, 3, 4 and 5) were
      identified in these fractions. PDE3 (cilostamide-sensitive), PDE4 (rolipram
      sensitive) and PDE5 (zaprinast- and DMPPO-sensitive) isoforms appeared as the
      main isozymes implicated in the cAMP and cGMP hydrolytic activities. Calcium
      camodulin stimulated PDE activity (PDE1) was mainly present in the cytosolic
      fraction. PDE2, although present, had a lower hydrolytic activity since addition
      of its specific inhibitor, erythro-9-(2-hydroxy-3nonyl)adenine (EHNA), to a
      combination of inhibitors of PDE3, 4 and 5 produced no further significant
      reduction in the enzymatic activity. Resolution of PDE activities from the
      cytosolic fraction using anion exchange chromatography confirmed this finding.
      Functional experiments performed in endothelium-denuded rings of rat MPA revealed
      that all specific PDE inhibitors used relaxed precontracted vascular smooth
      muscle preparations in a concentration-dependent manner. The rank order of
      potency was cilostamide >zaprinast>rolipram>>EHNA. The present study demonstrates
      the presence in the smooth muscle cells-containing layer of MPA of PDE1, 3, 4 and
      5 isoforms and suggests that PDE3, 4 and 5 are the main enzymes involved in the
      control of vascular tone.

PMID- 12007580
TI  - Methionine synthase. a possible prime site of the ethanolic lesion in liver.
AB  - Among the most important pathways for liver integrity in the body are the two
      that synthesize methionine and S-adenosylmethionine (SAM) through methylation of
      homocysteine. Results of studies in this laboratory have demonstrated ethanolic
      inhibition of one of these pathways catalyzed by methionine synthetase. It has
      been shown elsewhere that alcohol per se does not inhibit the enzyme, but that
      the metabolite of ethanol, acetaldehyde, is responsible through the formation of
      an inhibiting covalent adduct. Because hepatic SAM has been shown to be essential
      in the transport of fat from the liver, avoiding steatosis and further liver
      damage, it is entirely feasible that this repression of methionine synthase is an
      important site of the injurious action of alcohol metabolism in the liver. This
      loss of activity is particularly important in human beings who cannot produce
      methionine and SAM by means of the alternate pathway mediated by
      betaine:homocysteine:transmethylase, because of the lack of production of the
      betaine substrate for this enzyme.

PMID- 12007581
TI  - Aversion to acetaldehyde: differences in low-alcohol-drinking (UChA) and high
      alcohol-drinking (UChB) rats.
AB  - We have previously found the existence of a relation between activity of the
      brain mitochondrial aldehyde dehydrogenase (ALDH2) and consumption of ethanol in
      rats of the low-alcohol-drinking (UChA) and the high-alcohol-drinking (UChB)
      strains. The aim of the present study was to determine whether UChA and UChB rats
      also differed in sensitivity to the aversive effects of acetaldehyde (AcH).
      Aversion to AcH was studied by using a conditioned taste aversion (CTA) paradigm.
      Ethanol naive UChA and UChB rats were administered AcH intraperitoneally (50,
      100, or 150 mg/kg) or saline and exposed to a banana-flavored solution during
      five conditioning trials. A strong dose-dependent CTA to AcH was found in UChA
      rats, whereas UChB rats did not show a CTA to any dose of AcH. At equal doses of
      AcH, cerebral venous blood AcH levels in UChA rats were consistently higher than
      in UChB rats, a finding that may reflect the previously observed differences in
      the activity of ALDH2 between these strains. However, this observation is
      unlikely to explain fully the differences observed because aversion to AcH was
      developed in the UChA strain at blood levels of AcH that did not produce any
      aversion in the UChB strain. These results support the suggestion that, for the
      first time, differences in central or systemic effects of AcH per se may play a
      major role in determining the aversion to AcH in drinker and nondrinker animals.

PMID- 12007582
TI  - Influence of prenatal ethanol exposure on vascular contractile response in rat
      thoracic aorta.
AB  - Fetal alcohol syndrome is associated with cardiovascular malformation. However,
      the impact of prenatal ethanol exposure on vascular function is not clear. The
      purpose of this study was to examine the influence of prenatal ethanol exposure
      on vascular response in adulthood. Timed-pregnancy, female rats were fed an
      ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control
      diet from gestation day 2 until labor. The pups continued to receive a standard
      rat chow through adulthood, and the force-generating capacity of aortic ring
      segments was examined. Prenatal ethanol exposure did not significantly affect
      postnatal growth, but it did lead to elevated blood pressure in adulthood. The
      contractile response to potassium chloride was similar in vessels with intact
      endothelium, although the median effective concentration (EC(50)) was
      significantly reduced by prenatal ethanol exposure in rings with denuded
      endothelium. The response to norepinephrine was attenuated by prenatal ethanol
      exposure in rings with either intact or denuded endothelium. The endothelium
      dependent relaxation to carbamylcholine chloride was significantly attenuated by
      prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium
      nitroprusside or beta-adrenergic agonist isoproterenol was similar between
      control and prenatal-ethanol-exposed groups with either intact or denuded
      endothelium. Ethanol elicited a dose-dependent endothelium-dependent
      vasorelaxation, which was comparable between the two animal groups. The ethanol
      induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide
      synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to
      indicate that prenatal ethanol exposure contributes to alterations of both
      endothelium-dependent and endothelium-independent vascular contractile responses.

PMID- 12007583
TI  - Estradiol protects against cerebellar damage and motor deficit in ethanol
      withdrawn rats.
AB  - On the basis of findings obtained from this study, we hypothesize that the female
      sex steroid 17beta-estradiol (E(2)) protects against cerebellar neuronal damage
      and behavioral deficit in rats withdrawn from chronic ethanol exposure.
      Ovariectomized rats implanted with E(2) or an oil pellet received liquid ethanol
      (7.5% [wt./vol.]) or dextrin diet for 5 weeks, followed by 2 weeks of ethanol
      withdrawal. On termination of diet administration, rats were tested for both
      overt withdrawal signs and latency (seconds) to fall from an accelerating rotarod
      in six consecutive sessions (the longer the latency, the better the performance).
      The initial latency was measured separately to assess motoric capacity before
      learning occurred. Rats were then killed, and cerebella were prepared for
      accessing of Purkinje cell damage. The study revealed three specific findings.
      (1) In the absence of E(2), the ethanol withdrawal group showed higher total
      ethanol withdrawal sign scores than those for the dextrin group, whereas the
      score for the ethanol withdrawal group was lower in the presence of E(2). (2) In
      the absence of E(2), the ethanol withdrawal group showed shorter rotarod latency
      than that for the dextrin group, whereas the latency for the ethanol withdrawal
      group increased in the E(2)-treated group. In ethanol withdrawal groups, E(2)
      treatment also resulted in a longer latency than that observed with oil treatment
      in the initial session and in subsequent sessions. (3) Purkinje cell numbers in
      the ethanol withdrawal group without E(2) were lower than those in dextrin groups
      and in the ethanol withdrawal group with E(2) treatment. These findings support
      the suggestion that E(2) exerts protective effects against withdrawal signs,
      cerebellar neuronal damage, and motoric impairment in subjects exposed to, and
      withdrawn from, chronic ethanol exposure.

PMID- 12007584
TI  - Reinstatement of ethanol seeking responding after ethanol self-administration.
AB  - Understanding the processes related to resumption of alcohol-seeking behavior
      after a small, single exposure to alcohol could be important in treating
      alcoholic relapse. We used a new ethanol self-administration model to determine
      the potential role of ethanol self-administration in reinstatement of seeking
      behavior. Long-Evans rats were initiated to self-administer either 10% ethanol or
      3% sucrose in a sipper procedure. This procedure required that the rat make a
      fixed number of lever presses to gain access to a sipper tube for 20 min.
      Patterns of responding and tube-licking as well as volume intakes were recorded.
      Both within-session and across-session extinction/reinstatement procedures were
      tested with a brief ethanol self-administration exposure as the reinstatement
      event. Self-administration of small amounts of 10% ethanol (1.3 ml) in ethanol
      trained rats and small amounts of 3% sucrose (1.4 ml) in sucrose-trained rats
      resulted in modest reinstatement lever pressing. Although some reinstatement
      occurred, the amounts of lever pressing were minimal. These findings support the
      suggestion that self-administered ethanol in this experimental paradigm does not
      increase ethanol-seeking behavior.

PMID- 12007585
TI  - Ethanol consumption in the female Long-Evans rat: a modulatory role of estradiol.
AB  - The examination of various gonadal hormone manipulations on ethanol intake in
      human subjects and in rodent models has resulted in disparate findings. In the
      present study, we examined the effects of ovariectomy and subsequent estradiol
      (E(2)) replacement on ethanol intake in a within-subject design, as well as
      assessed the relevance of reproductive status on the efficacy of an E(2) stimulus
      in eliciting consumption. Female Long-Evans rats (n = 24) were given access to
      10% ethanol and water in a continuous-access paradigm. After establishment of
      baseline intake values, rats were divided into four groups: sham/placebo (Shm+P),
      sham/estradiol (Shm+E(2)), ovariectomized/placebo (Ovx+P), and
      ovariectomized/estradiol (Ovx+E(2)). Rats in the Ovx+P group were found to have a
      large and permanent decline in ethanol intake that persisted more than 3 months
      postsurgery. Administration of E(2) to Ovx+E(2) rats was associated with
      restoration of ethanol consumption to baseline levels. When Shm+E(2) and Ovx+E(2)
      groups were compared, reproductive status was found to be a determining factor in
      the efficacy of E(2) to elicit ethanol intake. Together, these findings provide
      evidence that ovarian hormones, particularly estradiol, exert activational
      effects on estrogen-responsive substrates to modulate ethanol consumption in the
      adult female rat.

PMID- 12007586
TI  - Effect of ethanol on axonal transport of cholinergic enzymes in rat sciatic
      nerve.
AB  - The aim of this study was to investigate whether the fast axonal transport of
      acetylcholinesterase (AChE) and the slow transport of choline acetyltransferase
      (ChAT) in the sciatic nerve of the rat are affected by chronic ethanol
      consumption or by associated nutritional deficiency. Adult rats drank ethanol
      (20% [vol./vol.]) instead of water for 20 weeks. Animals that consumed an
      isocaloric diet, representing a nutritional deficiency, received the same amount
      of food as ethanol-treated rats and water with sucrose replacing ethanol
      isocalorically. The control group received food and water ad libitum. Axonal
      transport was investigated by the stop-flow ligation technique as follows. After
      20 weeks, the sciatic nerve was ligated for 24 h, and accumulation of AChE and
      ChAT was measured above and below the ligature. No significant differences in the
      accumulation of both enzymes were found above the ligature. However, the
      accumulation of AChE transported retrogradely below the nerve ligature was
      reduced by 60%, but only in ethanol-treated animals. Our study results seem to
      indicate that, under experimental conditions, (1) neither ethanol nor associated
      nutritional deficiency has any effect on anterograde axonal transport of AChE and
      ChAT and (2) the deficit in retrograde transport of AChE is due to the direct
      toxic effect of ethanol and probably precedes the axonal degeneration from the
      most distal portions of axons toward the cell body.

PMID- 12007587
TI  - A relation between maze performance and increased ethanol intake in Long-Evans
      rats.
AB  - In addition to the neurochemical and genetic basis of high ethanol consumption,
      there has been renewed interest in studying the role of behavioral variables and
      their relation to ethanol consumption. The present study was designed to assess
      whether a relation exists between a behavioral variable such as maze learning
      ability and ethanol consumption. Sixty, male, Long-Evans rats, exposed to food
      and water ad libitum, were given a daily trial in a complex, 16-arm T-maze for 19
      consecutive days. The number of errors and time to complete the maze were
      monitored. Individual maze variable scores were transformed and then combined to
      allot each animal with an index of overall maze performance, with a smaller maze
      index score denoting good performance. After completion of maze testing, animals
      were given alternate-day, free-choice presentations of water and ascending doses
      of ethanol solutions (2%-10%), followed by a 10-day maintenance period with 10%
      ethanol. Animals were subsequently separated into two groups of high and low
      drinkers to examine any relation between differential ethanol intake and maze
      performance. A significant negative correlation between maze index and ethanol
      intake for the high drinkers group indicated that a smaller maze index was
      related to increased ethanol intake. No significant correlation was obtained for
      the low drinkers group. These results seem to indicate that individual variation
      in learning ability seems to be related to increased ethanol intake. Thus, innate
      learning processes may be a relevant trait when one attempts to understand the
      behaviors related to ethanol intake and preference.

PMID- 12007588
TI  - CSF hypocretin-1 levels in schizophrenics and controls: relationship to sleep
      architecture.
AB  - Hypocretins/orexins are newly identified peptides of hypothalamic origin.
      Hypocretin deficiency is involved in the sleep disorder narcolepsy, suggesting
      the importance of hypocretin neurotransmission for the regulation of sleep.
      Hypocretin is known to excite midbrain dopaminergic neurons and to induce
      hyperactivity and stereotypy in animals. Altered hypocretin neurotransmission
      might therefore be involved in schizophrenia, since an involvement of
      dopaminergic mechanisms and an association with sleep disturbance are well
      demonstrated in patients with schizophrenia. Hypocretin is also known to affect
      the hypothalamic-pituitary-adrenal axis by stimulating the release of
      corticotropin releasing hormone (CRH). In the current study, we measured CSF
      hypocretin levels in 12 controls and 13 patients with chronic schizophrenia
      associated with moderate sleep disturbance, such as longer sleep onset latency,
      decreased total sleep time and decreased sleep efficacy. No difference in CSF
      hypocretin levels between schizophrenia and control subjects was found. CSF
      hypocretin levels were positively correlated with CSF CRH levels in the patient,
      control and combined subject populations, but the correlation did not reach
      statistical significance in any population. The hypocretin levels in
      schizophrenic patients were, however, positively and significantly correlated
      with sleep latency, one of the most consistent sleep abnormalities seen in
      schizophrenia. This correlation was not significant in controls, and no other
      significant correlation between CSF hypocretin levels and any measure of sleep
      architecture in either patients or controls was observed. Further studies of
      whether CNS hypocretin neurotransmission is involved in sleep and neuroendocrine
      abnormalities seen in patients with schizophrenia and other psychiatric
      conditions are warranted.

PMID- 12007589
TI  - Changes in central serotonergic function as a correlate of duration of illness in
      paranoid schizophrenia.
AB  - There is evidence that the duration of untreated psychosis may affect both the
      course and outcome of treatment in schizophrenic patients. In the present study,
      we used neuroendocrine probes to test the hypothesis that untreated psychosis may
      induce time-dependent changes in central serotonergic and dopaminergic
      neurotransmission. Prolactin responses to the administration of clomipramine
      (i.v.) and haloperidol (i.m.) were measured in healthy control subjects and in 16
      never-treated male patients with DSM-IV diagnoses of schizophreniform or
      schizophrenic disorders of paranoid subtype, both before and after 5 weeks of
      treatment with haloperidol. In the drug-free state, schizophrenic patients
      exhibited significantly increased prolactin responses to clomipramine
      administration compared with both the healthy control subjects and the
      schizophreniform patients. Maximum prolactin responses to clomipramine in the
      total group of patients were positively correlated with the duration of psychotic
      illness and negatively correlated with changes in Positive and Negative Syndrome
      Scale (PANSS) total, negative symptoms and general psychopathology scores after 5
      weeks of treatment with haloperidol. Prolactin responses to haloperidol challenge
      in the drug-free state were lower in the schizophreniform group than in the
      control and the schizophrenic groups, but the differences did not reach
      statistical significance. The results provide evidence that the persistence of
      psychotic psychopathology induces secondary neuroadaptive effects, which seem to
      involve changes in central serotonergic function.

PMID- 12007590
TI  - Polymorphism of CTLA-4 gene at position 49 of exon 1 may be associated with
      schizophrenia in the Korean population.
AB  - This study was carried out to investigate the association of a polymorphism of
      the CTLA-4 gene, at position 49 of exon 1, with schizophrenia in the Korean
      population. Among Korean patients diagnosed with schizophrenia according to DSM
      IV, 116 patients who met the selection criteria were recruited for the study. One
      hundred and forty-nine normal healthy Koreans from the Catholic Hemopoietic Stem
      Cell Information Bank, were used as a normal control group. DNA was extracted
      from whole blood using proteinase K and the CTLA-4 gene region was amplified by
      polymerase chain reaction. Geneo typing was performed by single strand
      conformation polymorphism (SSCP). The genotype and allele distribution in
      patients with schizophrenia was significantly different from that seen in the
      control group. This study suggests a putative role of the CTLA-4 gene
      polymorphism at position 49 of exon 1 for schizophrenia in the Korean population,
      although the detailed mechanisms remained to be elucidated.

PMID- 12007591
TI  - Sex differences in clinical response to olanzapine compared with haloperidol.
AB  - There is current disagreement over whether men and women respond differently to
      typical or atypical antipsychotic medications. This study reanalyzed a large
      international clinical trial of olanzapine (Olz) compared with haloperidol (Hal)
      to test for sex differences in treatment response, controlling for illness
      chronicity and menopausal status. We hypothesized that women would show a greater
      response to either medication than men, particularly among first admission,
      premenopausal women. DSM-III-R schizophrenia inpatients (700 women and 1295 men)
      were randomly assigned to a 6-week trial of Olz vs. Hal. Longitudinal random
      effect models were used to test for interactions of sex with medication,
      chronicity and menopausal status on treatment response. Findings showed that
      women on olanzapine had a greater drop in overall symptomatology by week 4 than
      any other group, and their level of symptomatology remained lower throughout the
      6-week trial. The sex differences in treatment response in olanzapine compared
      with haloperidol were, in part, dependent on chronicity and, in women, menopausal
      status. That is, first episode women on haloperidol exhibited an increase in
      symptomatology over the 6-week trial compared to their male counterparts, while
      multiply hospitalized women had a better treatment response on haloperidol than
      their male counterparts. Women on olanzapine had a significantly better treatment
      response than men, regardless of chronicity. Finally, premenopausal women had a
      significantly better treatment response than postmenopausal women, regardless of
      treatment and chronicity.

PMID- 12007592
TI  - Indicators of medication compliance in first-episode psychosis.
AB  - Compliance behaviour is a multi-factorial phenomenon. In psychotic patients, it
      includes patient-related, medication-related, and environmental components.
      Compliance is a crucial factor in relation to outcome. The aim of this study was
      to explore indicators of compliance in a sample of 59 patients with a first-onset
      psychosis during their initial phase of treatment. Dependent variables in the
      logistic regression analysis included predictions made by the patients about
      their compliance in the initial phase and the observed compliance during the
      first 3 months according to patient record data. Explanatory variables comprised
      age, sex, living situation, education and social activities, Positive and
      Negative Syndrome Scale (PANSS) score, Hamilton Depression Scale score, Global
      Assessment of Functioning Scale score, Strauss-Carpenter Outcome Scale score,
      self-rated side effects, and insight and treatment-related variables. Predictions
      made by the patients about their compliance were determined by their self-rated
      attitude and insight measures. Determinants of observed non-compliance included
      experienced harmful side effects, male sex, lack of social activities, low score
      on PANSS positive symptoms, high PANSS total score and young age. The duration of
      untreated psychosis was not associated with compliance. Indicators of compliance
      in first-episode psychosis resemble those in the overall psychotic population.
      During the acute phase of psychosis, insight and attitudes toward treatment are
      the sole determinants of the patients' prediction of compliance.

PMID- 12007593
TI  - Working memory correlates of three symptom clusters in schizophrenia.
AB  - This study was designed to examine whether discrete working memory deficits
      underlie positive, negative and disorganised symptoms of schizophrenia. Symptom
      dimension ratings were assigned to 52 outpatients with schizophrenia (ICD-10
      criteria), using items drawn from the Positive and Negative Syndrome Scale
      (PANSS). Linear regression and correlational analyses were conducted to examine
      whether symptom dimension scores were related to performance on several tests of
      working memory function. Severity of negative symptoms correlated with reduced
      production of words during a verbal fluency task, impaired ability to hold letter
      and number sequences on-line and manipulate them simultaneously, reduced
      performance during a dual task, and compromised visuospatial working memory under
      distraction-free conditions. Severity of disorganisation symptoms correlated with
      impaired visuospatial working memory under conditions of distraction, failure of
      inhibition during a verbal fluency task, perseverative responding on a test of
      set-shifting ability, and impaired ability to judge the veracity of simple
      declarative statements. Severity of positive symptoms was uncorrelated with
      performance on any of the measures examined. The present study provides evidence
      that the positive, negative and disorganised symptom dimensions of the PANSS
      constitute independent clusters, associated with unique patterns of working
      memory impairment.

PMID- 12007594
TI  - Error-related brain activity in obsessive-compulsive undergraduates.
AB  - Error-related negativity (ERN/Ne) is a component of the event-related brain
      potential (ERP) associated with monitoring action and detecting errors. It is a
      sharp negative deflection that generally occurs from 50 to 150 ms following
      response execution and has been associated with activity involving the anterior
      cingulate cortex (ACC). An enhanced ERN has recently been observed in patients
      with obsessive-compulsive disorder (OCD). We extended these findings by measuring
      the ERN in college undergraduates with OC characteristics as measured by the
      Obsessive-Compulsive Inventory (OCI). Eighteen high-OC subjects and 17 low-OC
      subjects performed a modified Stroop task with equal emphasis placed on speed and
      accuracy. Response-locked ERPs revealed a frontally maximal negativity associated
      with erroneous responses that was significantly larger in the high-OCI group.
      There were no performance differences between the two groups. Our results support
      the view that the characteristics associated with OCD are related to hyper
      functioning error and action-monitoring processes.

PMID- 12007595
TI  - Psychiatric disorders in asthmatic outpatients.
AB  - It has been reported that the lifetime prevalence of panic disorder in patients
      with pulmonary disease is higher than epidemiologic estimates of population
      prevalence. We evaluated the frequency of anxiety disorders in 86 subjects from
      the Outpatient Asthma Clinic. Psychiatric diagnoses were assessed with the Mini
      International Neuropsychiatric Interview 4.4 Version (MINI). Forty-five asthmatic
      patients (52.3%) reported at least one current anxiety disorder. The frequency of
      panic disorder with or without agoraphobia was 13.9% (n=12) and that of
      agoraphobia without panic disorder was 26.8% (n=23). Social anxiety and
      generalized anxiety disorders occurred in 9.3% (n=8) and 24.4% (n=21) of the
      sample, respectively. Twenty-nine patients (33.7%) reported a major depressive
      episode. The psychiatric morbidity of the sample was 61.6% (n=53). Our results
      tend to support the high morbidity of anxiety disorders, particularly
      panic/agoraphobic spectrum disorders, in asthmatic outpatients.

PMID- 12007596
TI  - Absence of selected neurological soft signs in Vietnam nurse veterans with post
      traumatic stress disorder.
AB  - This study examined eight neurological soft signs (NSSs), which had previously
      proved successful in discriminating medication-free post-traumatic stress
      disorder (PTSD) from non-PTSD combat veterans and sexually abused women, in 82
      unmedicated female nurse Vietnam veterans, 32 with and 50 without PTSD. The
      increased NSSs observed in the previously studied PTSD samples were not found in
      the nurses with PTSD. The results fail to support the hypothesis that the stress
      of a traumatic event and/or resultant PTSD damages the nervous system.

PMID- 12007597
TI  - Family history of suicide and neuroticism: a preliminary study.
AB  - Whether a family history of suicide (FHS) might increase the risk for suicidal
      behavior through an effect on personality was examined. Patients with a first or
      second-degree relative who had committed suicide were compared with matched
      patients with a negative FHS for their scores on the Eysenck Personality
      Questionnaire (EPQ). The trend for a difference on EPQ neuroticism scores between
      the total groups became significant when subgroups of FHS positive and negative
      patients, who had no personal history of attempting suicide, were compared.
      Further studies of the relationship of a family history of suicide to personality
      are needed in other populations and incorporating biologic measures.

PMID- 12007598
TI  - Crystallization and preliminary X-ray crystallographic analysis of Ace: a
      collagen-binding MSCRAMM from Enterococcus faecalis.
AB  - Ace is a collagen-binding bacterial cell surface adhesin from Enterococcus
      faecalis. The collagen-binding domain of Ace (termed Ace40) and its truncated
      form Ace19 have been crystallized by the vapor-diffusion hanging-drop method.
      Ace19 was crystallized in two different crystal forms. A complete 1.65 A data set
      has been collected on the orthorhombic crystal form with unit cell parameters
      a=38.43 b=48.91 and c=83.73 A. Ace40 was crystallized in the trigonal space group
      P3(1)21 or P3(2)21 with unit cell parameters a=b=80.24, c=105.91 A; alpha=beta=90
      and gamma=120 degrees. A full set of X-ray diffraction data was collected to 2.5
      A. Three heavy atom derivative data sets have been successfully obtained for
      Ace19 crystals and structural analysis is in progress.

PMID- 12007599
TI  - Preliminary crystallographic studies of Limulus polyphemus hemocyanin subunits
      IIIa, IIIb and IV.
AB  - Crystals of Limulus hemocyanin subunits IIIa, IIIb and IV are suitable for X-ray
      diffraction analysis. The three-dimensional structure of subunit IV is determined
      by molecular replacement and non-crystallographic symmetry averaging methods. A
      tentative model of subunit IIIa is obtained from a partial data set. Both
      structures, similar to subunit II, could provide primary structure segments
      suitable for oligonucleotide probe synthesis.

PMID- 12007600
TI  - The blockage of the high-affinity lysine binding sites of plasminogen by EACA
      significantly inhibits prourokinase-induced plasminogen activation.
AB  - Prourokinase-induced plasminogen activation is complex and involves three
      distinct reactions: (1) plasminogen activation by the intrinsic activity of
      prourokinase; (2) prourokinase activation by plasmin; (3) plasminogen activation
      by urokinase. To further understand some of the mechanisms involved, the effects
      of epsilon-aminocaproic acid (EACA), a lysine analogue, on these reactions were
      studied. At a low range of concentrations (10-50 microM), EACA significantly
      inhibited prourokinase-induced (Glu-/Lys-) plasminogen activation, prourokinase
      activation by Lys-plasmin, and (Glu-/Lys-) plasminogen activation by urokinase.
      However, no inhibition of plasminogen activation by Ala158-prourokinase (a
      plasmin-resistant mutant) occurred. Therefore, the overall inhibition of EACA on
      prourokinase-induced plasminogen activation was mainly due to inhibition of
      reactions 2 and 3, by blocking the high-affinity lysine binding interaction
      between plasmin and prourokinase, as well as between plasminogen and urokinase.
      These findings were consistent with kinetic studies which suggested that binding
      of kringle 1-4 of plasmin to the N-terminal region of prourokinase significantly
      promotes prourokinase activation, and that binding of kringle 1-4 of plasminogen
      to the C-terminal lysine158 of urokinase significantly promotes plasminogen
      activation. In conclusion, EACA was found to inhibit, rather than promote,
      prourokinase-induced plasminogen activation due to its blocking of the high
      affinity lysine binding sites on plasmin(ogen).

PMID- 12007601
TI  - Novel anti-inflammatory compounds from Rubus sieboldii, triterpenoids, are
      inhibitors of mammalian DNA polymerases.
AB  - Two anti-inflammatory triterpenoids, tormentic acid (TA) and euscaphic acid (EA),
      were found from the plant Rubus sieboldii. These triterpenoids showed an
      inhibitory effect against enzymes involved in replication, such as calf DNA
      polymerase alpha (pol alpha) and rat DNA polymerase beta (pol beta). The IC50
      values of TA and EA were 37 and 61 microM for pol alpha and 46 and 108 microM for
      pol beta, respectively. However, TA and EA did not influence the activities of
      plant DNA polymerases, DNA primase, human immunodeficiency virus type-1 reverse
      transcriptase, terminal deoxynucleotidyl transferase, any of the prokaryotic DNA
      polymerases or DNA and RNA metabolic enzymes tested. TA and EA could prevent the
      growth of BALL-1 cancer cells, and the LD50 values were 11 and 48 microM,
      respectively. The cells were halted at G1 phase in the cell cycle. The mode of
      action of the triterpenoids against anti-inflammatory activity and their
      relationships to the DNA polymerase inhibitory activity and cell growth
      inhibition were discussed.

PMID- 12007602
TI  - Kynurenine formamidase: determination of primary structure and modeling-based
      prediction of tertiary structure and catalytic triad.
AB  - Kynurenine formamidase (KFase) (EC 3.5.1.9) hydrolyzes N-formyl-L-kynurenine, an
      obligatory step in the conversion of tryptophan to nicotinic acid. Low KFase
      activity in chicken embryos, from inhibition by organophosphorus insecticides and
      their metabolites such as diazoxon, leads to marked developmental abnormalities.
      While KFase was purportedly isolated previously, the structure and residues
      important for catalysis and inhibition were not established. KFase was isolated
      here from mouse liver cytosol by (NH4)2SO4 precipitation and three FPLC steps
      (resulting in 221-fold increase in specific activity for N-formyl-L-kynurenine
      hydrolysis) followed by conversion to [3H]diethylphosphoryl-KFase and finally
      isolation by C4 reverse-phase high-performance liquid chromatography.
      Determination of tryptic fragment amino acid sequences and cDNA cloning produced
      a new 305-amino-acid protein sequence. Although an amidase by function, the
      primary structure of KFase lacks the amidase signature sequence and is more
      similar to esterases and lipases. Sequence profile analysis indicates KFase is
      related to the esterase/lipase/thioesterase family containing the conserved
      active-site serine sequence GXSXG. The alpha/beta-hydrolase fold is suggested for
      KFase by its primary sequence and predicted secondary conformation. A three
      dimensional model based on the structures of homologous carboxylesterase EST2 and
      brefeldin A esterase implicates Ser162, Asp247 and His279 as the active site
      triad.

PMID- 12007603
TI  - Enhanced response to antibody binding in engineered beta-galactosidase enzymatic
      sensors.
AB  - Peptide display on solvent-exposed surfaces of engineered enzymes allows them to
      respond to anti-peptide antibodies by detectable changes in their enzymatic
      activity, offering a new principle for biosensor development. In this work, we
      show that multiple peptide insertion in the vicinity of the Escherichia coli beta
      galactosidase active site dramatically increases the enzyme responsiveness to
      specific anti-peptide antibodies. The modified enzymes HD7872A and HT7278CA,
      carrying eight and 12 copies respectively of a foot-and-mouth disease peptide per
      enzyme molecule, show antibody-mediated activation factors higher than those
      previously observed in the first generation enzymatic sensors, for HT7278CA being
      close to 400%. The analysis of the signal transduction process with multiple
      inserted proteins strongly suggests a new, non-exclusive mechanism of enzymatic
      regulation in which the target proteins might be stabilised by the bound
      antibody, extending the enzyme half-life and consequently enhancing the signal
      background ratio. In addition, the tested sensors are differently responsive to
      sera from immune farm animals, depending on the antigenic similarity between the
      B-cell epitopes in the immunising virus and those in the peptide used as sensing
      element on the enzyme surface. Altogether, these results point out the utility of
      these enzymatic biosensors for a simple diagnosis of foot-and-mouth disease in an
      extremely fast homogeneous assay.

PMID- 12007604
TI  - Effect of dimethyl sulfoxide on the structure and the functional properties of
      horseradish peroxidase as observed by spectroscopy and cyclic voltammetry.
AB  - Electrochemical biosensors have found wide application in food and clinical
      areas, as well as in environmental field. A large number of articles focused on
      horseradish peroxidase (HRP)-based biosensors have been published in the last
      decade, due to the capability of HRP to quantitatively detect the presence of
      hydrogen peroxide produced in a reaction. At present a large body of multi
      enzymatic amperometric biosensors are realized by entrapping HRP together with
      other enzymes into a polymeric matrix; these systems represent a promising
      example of simple, low-cost electrochemical tools for the analysis of bioanalytes
      in solution, such as glucose, choline and cholesterol. Due to the fact that
      polymers used for HRP entrapping are soluble in organic solvents and that many
      solvents are strong denaturants of aquo-soluble proteins, in this paper we
      investigate (in particular, by circular dichroism and electron paramagnetic
      spectroscopies) the effect of dimethyl sulfoxide, one of the organic solvents
      employed for polymer solubilization, on the structure and the functionality of
      HRP, in order to determine the effect induced by the solvent concentration on the
      structure and activity of the hemoprotein. This is relevant for basic and applied
      biochemistry, HRP being largely employed in bioinorganic chemistry and sensor
      area.

PMID- 12007605
TI  - Enhancement of plasminogen activation by surfactin C: augmentation of
      fibrinolysis in vitro and in vivo.
AB  - The reciprocal activation of plasminogen and prourokinase (pro-u-PA) is an
      important mechanism in the initiation and propagation of local fibrinolytic
      activity. We have found that a bacterial lipopeptide compound, surfactin C (3-20
      microM), enhances the activation of pro-u-PA in the presence of plasminogen. This
      effect accompanied increased conversions of both pro-u-PA and plasminogen to
      their two-chain forms. Surfactin C also elevated the rate of plasminogen
      activation by two-chain urokinase (tcu-PA) while not affecting plasmin-catalyzed
      pro-u-PA activation and amidolytic activities of tcu-PA and plasmin. The
      intrinsic fluorescence of plasminogen was increased, and molecular elution time
      of plasminogen in size-exclusion chromatography was shortened in the presence of
      surfactin C. These results suggested that surfactin C induced a relaxation of
      plasminogen conformation, thus leading to enhancement of u-PA-catalyzed
      plasminogen activation, which in turn caused feedback pro-u-PA activation.
      Surfactin C was active in enhancing [125I]fibrin degradation both by pro-u
      PA/plasminogen and tcu-PA/plasminogen systems. In a rat pulmonary embolism model,
      surfactin C (1 mg/kg, i.v.) elevated 125I plasma clot lysis when injected in
      combination with pro-u-PA. The present results provide first evidence that
      pharmacological relaxation of plasminogen conformation leads to enhanced
      fibrinolysis in vivo.

PMID- 12007606
TI  - Molecular and functional properties of an archaeal phenylalanyl-tRNA synthetase
      from the hyperthermophile Sulfolobus solfataricus.
AB  - An archaeal phenylalanyl-tRNA synthetase (FRS) has been purified from the
      hyperthermophile Sulfolobus solfataricus (Ss). This enzyme is a heterotetramer
      made of two different subunits whose molecular mass is 56 kDa and 64 kDa,
      respectively. As thought, SsFRS is essential for the in vitro poly(Phe)
      synthesis. Interestingly, the enzyme is able to aminoacylate only endogenous tRNA
      but it does not seem to be a strictly ATP-dependent synthetase. SsFRS interacts
      with the elongation factor 1alpha isolated from the same source; this caused a
      significant enhancement of the SstRNA aminoacylation efficiency, thus indicating
      that, as well as in eukarya, in this archaeon a tRNA channelling mechanism should
      occur. The overall results presented in this paper show that the archaeal SsFRS
      behaves as the analogous enzymes isolated from eukaryal sources rather than those
      from eubacterial organisms.

PMID- 12007607
TI  - The surface exposed amino acid residues of monomeric proteins determine the
      partitioning in aqueous two-phase systems.
AB  - It is of great interest and importance how different amino acid residues
      contribute to and affect the properties of a protein surface. Partitioning in
      aqueous two-phase systems has the potential to be used as a rapid and simple
      method for studying the surface properties of proteins. The influence on
      partitioning of the surface exposed amino acid residues of eight structurally
      determined monomeric proteins has been studied. The proteins were characterized
      in terms of surface exposed residues with a computer program, Graphical
      Representation and Analysis of Surface Properties (GRASP), and partitioned in two
      EO30PO70-dextran aqueous two-phase systems, only differing in polymer
      concentrations (system I: 6.8% EO30PO70, 7.1% dextran; system II: 9% EO30PO70, 9%
      dextran). We show for the first time that the partitioning behaviour of different
      monomeric proteins can be described by the differences in surface exposed amino
      acid residues. The contribution to the partition coefficient of the residues was
      found to be best characterized by peptide partitioning in the aqueous two-phase
      system. Compared to hydrophobicity scales available in the literature, each amino
      acid contribution is characterized by the slope given by the graph of log K
      against peptide chain length, for peptides of different length containing only
      one kind of residue. It was also shown that each amino acid contribution is
      relative to the total protein surface and the other residues on the surface.
      Surface hydrophobicity calculations realized for systems I and II gave
      respectively correlation coefficients of 0.961 and 0.949 for the linear relation
      between log K and calculated hydrophobicity values. To study the effect on the
      partition coefficient of different amino acids, they were grouped into classes
      according to common characteristics: the presence of an aromatic group, a long
      aliphatic chain or the presence of charge. Using these groups it was possible to
      confirm that aromatic residues have the strongest effect on the partition
      coefficient, giving preference to the upper EO30PO70 phase of the system; on the
      other hand the presence of charged amino acids on the protein surface enhances
      the partition of the protein to the lower dextran phase. It is also important to
      note that the sensitivity of the EO30PO70-dextran system for the surface exposed
      residues was increased by increasing the polymer concentrations. The partition
      coefficient of a monomeric protein can thus be predicted from its surface exposed
      amino acid residues and the system can also be used to characterize protein
      surfaces of monomeric proteins in general.

PMID- 12007608
TI  - Cleavage specificity of the subtilisin-like protease C1 from soybean.
AB  - The cleavage specificity of protease C1, isolated from soybean (Glycine max (L.)
      Merrill) seedling cotyledons, was examined using oligopeptide substrates in an
      HPLC based assay. A series of peptides based on the sequence Ac-KVEKEESEEGE-NH2
      was used, mimicking a natural cleavage site of protease C1 in the alpha subunit
      of the storage protein beta-conglycinin. A study of substrate peptides truncated
      from either the N- or C-terminus indicates that the minimal requirements for
      cleavage by protease C2 are three residues N-terminal to the cleaved bond, and
      two residues C-terminal (i.e. P3-P2'). The maximal rate of cleavage is reached
      with substrates containing four to five residues N-terminal to the cleaved bond
      and four residues C-terminal (i.e. P4 or P5 to P4'). The importance of Glu
      residues at the P1, P1', and P4 positions was examined using a series of
      substituted nonapeptides (P5-P4') with a base sequence of Ac-KVEKEESEE-NH2. At
      the P1 position, the relative ranking, based on kcat/Km, was E>Q>K>A>D>F>S.
      Substitutions at the P1' position yield the ranking E congruent withQ>A>S>D>K>F,
      while those at P4' had less effect on kcat/Km, yielding the ranking F congruent
      with S congruent with E congruent withD>K>A congruent withQ. These data show that
      protease C1 prefers to cleave at Glu-Glu and Glu-Gln bonds, and that the nature
      of the P4' position is less important. The fact that there is specificity in the
      cleavage of the oligopeptides suggests that the more limited specific cleavage of
      the alpha and alpha' subunits of beta-conglycinin by protease C1 is due to a
      combination of the sequence cleavage specificity of the protease and the
      accessibility of appropriate scissile peptide bonds on the surface of the
      substrate protein.

PMID- 12007609
TI  - Cloning of human 3-hydroxyanthranilic acid dioxygenase in Escherichia coli:
      characterisation of the purified enzyme and its in vitro inhibition by Zn2+.
AB  - 3-hydroxyanthranilic acid oxygenase (3-HAO) catalyses the conversion of 3
      hydroxyanthranilic acid to quinolinic acid. Because of the involvement of
      quinolinic acid in the initiation of neurodegenerative phenomena, we have cloned
      human 3-HAO in Escherichia coli, overexpressed and purified it with the aim of
      studying its enzymatic activity and for future structural studies. The
      recombinant human protein, obtained in E. coli, retains its enzymatic activity
      which can occur only in the presence of Fe(II); several other metals have been
      tested but in no case the formation of the product has been observed. On the
      contrary, two of the ions tested inhibit the catalytic reaction and one of them,
      Zn2+, could be of physiological relevance. A circular dichroism analysis has also
      been performed, showing that the secondary structure is mainly of the beta type,
      with a minority of alpha.

PMID- 12007610
TI  - Calf spleen purine nucleoside phosphorylase: complex kinetic mechanism,
      hydrolysis of 7-methylguanosine, and oligomeric state in solution.
AB  - The active enzyme form was found to be a homotrimer, no active monomers were
      observed. Only in the presence of an extremely high orthophosphate concentration
      (0.5 M) or at a low enzyme concentration (0.2 microg/ml) with no ligands present
      a small fraction of the enzyme is probably in a dissociated and/or non-active
      form. The specific activity is invariant over a broad enzyme concentration range
      (0.017 microg/ml-0.29 mg/ml). At concentrations below 0.9 microg/ml and in the
      absence of ligands the enzyme tends to loose its catalytic activity, while in the
      presence of any substrate or at higher concentrations it was found to be active
      as a trimer. In the absence of phosphate the enzyme catalyses the hydrolysis of 7
      methylguanosine (m7Guo) with a catalytic rate constant 1.3x10(-3) x s(-1) as
      compared with the rate of 38 s(-1) for the phosphorolysis of this nucleoside. The
      initial pre-steady-state phase of the phosphorolysis of m7Guo, 70 s(-1), is
      almost twice faster than the steady-state rate and indicates that the rate
      limiting step is subsequent to the glycosidic bond cleavage. Complex kinetic
      behaviour with substrates of phosphorolytic direction (various nucleosides and
      orthophosphate) was observed; data for phosphate as the variable substrate with
      inosine and guanosine, but not with their 7-methyl counterparts, might be
      interpreted as two binding sites with different affinities, or as a negative
      cooperativity. However, the titration of the enzyme intrinsic fluorescence with
      0.2 microM-30 mM phosphate is consistent with only one dissociation constant for
      phosphate, K(d)=220+/-120 microM. Protective effects of ligands on the thermal
      inactivation of the enzyme indicate that all substrates of the phosphorolytic and
      the synthetic reactions are able to form binary complexes with the calf spleen
      purine nucleoside phosphorylase. The purine bases, guanine and hypoxanthine, bind
      strongly with dissociation constants of about 0.1 microM, while all other ligands
      studied, including 7-methylguanine and 7-methylhypoxanthine, bind at least 3
      orders of magnitude less potently. Binding of guanine and hypoxanthine is about
      10-fold weakened by the presence of phosphate. These observations are best
      interpretable by the complex kinetic mechanism of the phosphorolytic reaction
      involving (i) random substrate binding, (ii) unusually slow, hence strongly rate
      limiting, dissociation of the products guanine and hypoxanthine, but not 7
      methylguanine and 7-methylhypoxanthine, and (iii) dual function of the phosphate
      binding site with phosphate acting as a substrate and as a modifier helping in
      the release of a purine base after glycosidic bond cleavage.

PMID- 12007611
TI  - Effects of guanidine hydrochloride and high pressure on subsite flexibility of
      beta-amylase.
AB  - We investigated the effects of guanidine hydrochloride (GuHCl) and high pressure
      on the conformational flexibility of the active site of sweet potato beta-amylase
      by monitoring the sulfhydryl reaction and the enzymatic activity. The reactivity
      of Cys345 at the active site, one of six inert half cystine residues of this
      enzyme, was enhanced by GuHCl at concentrations below 0.5 M. A GuHCl-induced
      change of the active site was also observed through an intensity change in the
      near-UV circular dichroism (CD) spectrum. On the other hand, the native
      conformation of sweet potato beta-amylase observed through fluorescence
      polarization, far-UV CD spectrum and intrinsic fluorescence was not influenced by
      GuHCl at concentrations below 0.5 M. Therefore, Cys345 reaction caused by GuHCl
      was due to an alteration of the local conformation of the active site. GuHCl
      induced reaction of Cys345, located in the vicinity of subsites 3 and 4, is
      attributed to enhanced subsite flexibility, which is responsible for substrate
      slipping in a single-chain attack mechanism. Due to the flexible conformation,
      the local region of the subsite is more susceptible to GuHCl perturbation than
      the molecule overall. The enzymatic activity of sweet potato beta-amylase was
      reversibly inhibited by GuHCl at concentrations below 0.5 M, and kinetic analysis
      of the enzymatic mechanism showed that GuHCl decreases the kcat value. High
      pressure below 400 MPa also inactivated sweet potato beta-amylase with an
      increase in Cys345 reactivity. These findings indicated that excessively enhanced
      subsite flexibility reduced the enzymatic activity of sweet potato beta-amylase.

PMID- 12007612
TI  - New aspects on the mechanism of GroEL-assisted protein folding.
AB  - The mechanism of assisted protein folding by the chaperonin GroEL alone or in
      complex with the co-chaperonin GroES and in the presence or absence of
      nucleotides has been subject to extensive investigations during the last years.
      In this paper we present data where we have inactivated GroEL by stepwise
      blocking the nucleotide binding sites using the non-hydrolyzable ATP analogue,
      (Cr(H2O)4)3+ATP. We correlated the amount of accessible nucleotide binding sites
      with the residual ATP hydrolysis activity of GroEL as well as the residual
      refolding activity for two different model substrates. Under the conditions used,
      folding of the substrate proteins and ATP hydrolysis were directly proportional
      to the residual, accessible nucleotide binding sites. In the presence of GroES,
      50% of the nucleotide binding sites were protected from inactivation by CrATP and
      the resulting protein retains 50% of both ATPase and refolding activity. The
      results strongly suggest that under the conditions used in our experiments, the
      nucleotide binding sites are additive in character and that by blocking of a
      certain number of binding sites a proportional amount of ATP hydrolysis and
      refolding activities are inactivated. The experiments including GroES suggest
      that full catalytic activity of GroEL requires both rings of the chaperonin.
      Blocking of the nucleotide binding sites of one ring still allows function of the
      second ring.

PMID- 12007613
TI  - Crystal structure of the double azurin mutant Cys3Ser/Ser100Pro from Pseudomonas
      aeruginosa at 1.8 A resolution: its folding-unfolding energy and unfolding
      kinetics.
AB  - Azurin is a cupredoxin, which functions as an electron carrier. Its fold is
      dominated by a beta-sheet structure. In the present study, azurin serves as a
      model system to investigate the importance of a conserved disulphide bond for
      protein stability and folding/unfolding. For this purpose, we have examined two
      azurin mutants, the single mutant Cys3Ser, which disrupts azurin's conserved
      disulphide bond, and the double mutant Cys3Ser/Ser100Pro, which contains an
      additional mutation at a site distant from the conserved disulphide. The crystal
      structure of the azurin double mutant has been determined to 1.8 A resolution(2),
      with a crystallographic R-factor of 17.5% (R(free)=20.8%). A comparison with the
      wild-type structure reveals that structural differences are limited to the sites
      of the mutations. Also, the rates of folding and unfolding as determined by CD
      and fluorescence spectroscopy are almost unchanged. The main difference to wild
      type azurin is a destabilisation by approximately 20 kJ x mol(-1), constituting
      half the total folding energy of the wild-type protein. Thus, the disulphide bond
      constitutes a vital component in giving azurin its stable fold.

PMID- 12007614
TI  - Lys40 but not Arg143 influences selectivity of angiotensin conversion by human
      alpha-chymase.
AB  - Human alpha-chymase is an efficient angiotensin (AT) converting enzyme,
      selectively hydrolyzing AT I at Phe8 to generate bioactive AT II, which can
      promote cardiac hypertrophy, vascular stenosis, and hypertension. Some related
      enzymes, such as rat beta-chymase 1, are much less selective, destroying AT by
      cleaving at Tyr4. Comparisons of chymase structure and activity led to
      speculation that interaction between AT and the side chain of Lys40 or Arg143
      accounts for the human enzyme's marked preference for Phe8 over Tyr4. To test
      these hypotheses, we compared AT hydrolysis by wild-type chymase with that by
      mutants changing Lys40 or Arg143 to neutral residues. Lys40 was exchanged for
      alanine, the residue found in canine alpha- and rat beta-chymase 1, the latter
      being dramatically less selective for hydrolysis at Phe8. Arg143 was exchanged
      for glutamine found in rat beta-chymase 1. The Lys40Ala mutant is a dog-like
      enzyme retaining strong preference for Phe8 but with Tyr4 hydrolytic rates
      enhanced 16-fold compared to wild-type human enzyme. Thus, of 40 residues
      mismatched between dog and human enzymes, a single residue accounts for most of
      the difference in specificity between them. The Arg143Gln mutant, contrary to
      prediction, remains highly Phe8-selective. Therefore, Lys40, but not Arg143,
      contributes to human chymase's remarkable preference for AT II generation over
      destruction.

PMID- 12007615
TI  - Microcalorimetric study of elongation factor Tu from Thermus thermophilus in
      nucleotide-free, GDP and GTP forms and in the presence of elongation factor Ts.
AB  - Elongation factor (EF) Tu undergoes profound nucleotide-dependent conformational
      changes in its functional cycle. The thermodynamic parameters of the different
      Thermus thermophilus EF-Tu forms, its domains I, II/III and III, were determined
      by microcalorimetry. Thermal transitions of the EF-Tu.GDP and EF-Tu.guanosine-5'
      [beta,gamma-imido]triphosphate have a cooperative two-state character. Nucleotide
      removal affected the cooperativity of the thermal transition of EF-Tu.
      Microcalorimetric measurements of nucleotide-free EF-Tu and its separated domains
      showed that domains II/III have the main stabilizing role for the whole protein.
      Despite the fact that strong interactions between elongation factors Tu and Ts
      from T. thermophilus at 20 degrees C exist, the thermal transition of neither
      protein in the complex was significantly affected.

PMID- 12007616
TI  - Kinetic parameters and mode of action of the cellobiohydrolases produced by
      Talaromyces emersonii.
AB  - Three forms of cellobiohydrolase (EC 3.2.1.91), CBH IA, CBH IB and CBH II, were
      isolated to apparent homogeneity from culture filtrates of the aerobic fungus
      Talaromyces emersonii. The three enzymes are single sub-unit glycoproteins, and
      unlike most other fungal cellobiohydrolases are characterised by noteworthy
      thermostability. The kinetic properties and mode of action of each enzyme against
      polymeric and small soluble oligomeric substrates were investigated in detail.
      CBH IA, CBH IB and CBH II catalyse the hydrolysis of microcrystalline cellulose,
      albeit to varying extents. Hydrolysis of a soluble cellulose derivative (CMC) and
      barley 1,3;1,4-beta-D-glucan was not observed. Cellobiose (G2) is the main
      reaction product released by CBH IA, CBH IB, and CBH II from microcrystalline
      cellulose. All three CBHs are competitively inhibited by G2; inhibition constant
      values (K(i)) of 2.5 and 0.18 mM were obtained for CBH IA and CBH IB,
      respectively (4-nitrophenyl-beta-cellobioside as substrate), while a K(i) of 0.16
      mM was determined for CBH II (2-chloro-4-nitrophenyl-beta-cellotrioside as
      substrate). Bond cleavage patterns were determined for each CBH on 4
      methylumbelliferyl derivatives of beta-cellobioside and beta-cellotrioside
      (MeUmbG(n)). While the Tal. emersonii CBHs share certain properties with their
      counterparts from Trichoderma reesei, Humicola insolens and other fungal sources,
      distinct differences were noted.

PMID- 12007617
TI  - Inhibition of yeast lipase (CRL1) and cholesterol esterase (CRL3) by 6-chloro-2
      pyrones: comparison with porcine cholesterol esterase.
AB  - Previously, it was demonstrated that pancreatic cholesterol esterase is
      selectively inhibited by 6-chloro-2-pyrones with cyclic aliphatic substituents in
      the 3-position. Inhibition is reversible and is competitive with substrate.
      Pancreatic cholesterol esterase is a potential target for treatment of
      hypercholesterolemia. In the present study, yeast cholesterol esterase from
      Candida cylindracea (also called C. rugosa CRL3) was compared to porcine
      pancreatic cholesterol esterase for inhibition by a series of 3-alkyl- or 5-alkyl
      6-chloro-2-pyrones. In addition, CRL3 was compared with the related yeast lipase
      CRL1. Inhibition of CRL3 by substituted 6-chloro-2-pyrones was competitive with
      binding of the substrate p-nitrophenyl butyrate. Inhibition constants ranged from
      0.2 microM to >90 microM. Small changes in the alkyl group had profound effects
      on binding. The pattern of inhibition of CRL3 is quite distinct from that
      observed with porcine cholesterol esterase. Molecular modeling studies suggest
      that the orientation of binding of these inhibitors at the active site of CRL3
      can vary but that the pyrone ring consistently occupies a position close to the
      active site serine. CRL1 is highly homologous to CRL3. Nevertheless, patterns of
      inhibition of CRL1 by substituted 6-chloro-2-pyrones differ markedly from
      patterns observed with CRL3. The substituted 6-chloro-2-pyrones are slowly
      hydrolyzed in the presence of CRL1 and are pseudosubstrates of CRL3, but are
      simple reversible inhibitors of pancreatic cholesterol esterase

PMID- 12007618
TI  - Potassium permeation through the KcsA channel: a density functional study.
AB  - We present a theoretical study on structural and electronic aspects of K+
      permeation through the binding sites of the KcsA channel's selectivity filter.
      Density functional calculations are carried out on models taken from selected
      snapshots of a molecular dynamics simulation recently reported [FEBS Lett. 477
      (2000) 37]. During the translocation process from one binding site to the other,
      the coordination number of the permeating K+ ion turns out to decrease and K+ ion
      polarizes significantly its ligands, backbone carbonyl groups and a water
      molecule. K+-induced polarization increases significantly at the transition state
      (TS) between the two binding sites. These findings suggest that polarization
      effects play a significant role in the microscopic mechanisms regulating
      potassium permeation.

PMID- 12007619
TI  - Listeriolysin O-liposome-mediated cytosolic delivery of macromolecule antigen in
      vivo: enhancement of antigen-specific cytotoxic T lymphocyte frequency, activity,
      and tumor protection.
AB  - Cytotoxic T lymphocytes (CTLs) are primed by peptide antigens that are
      endogenously processed in the cytosol and presented in the context of major
      histocompatibility complex I (MHC I) molecules of antigen-presenting cells
      (APCs). Exogenous soluble protein antigens do not gain efficient entry into the
      cytosol of APCs, and therefore requires a special cytosolic delivery method. We
      have developed such a delivery strategy adopting the well-elucidated cytosol
      invading listerial endosomal escape mechanism, and report here an efficient
      delivery of exogenous whole protein antigen into the cytosol in a mouse model. Co
      encapsulation of listeriolysin O (LLO) inside liposome (LLO-liposome) was
      required for delivery of ovalbumin (OVA) into the cytosol of APCs in primary
      cultures. LLO-liposome-mediated OVA immunization in mice engendered significantly
      higher OVA-specific CTL activity and increased antigenic peptide-specific CTL
      precursor (CTLp) frequency as compared to non-LLO-liposome or soluble OVA
      immunizations. Interferon-gamma (IFN-gamma) production upon specific stimulation
      by MHC I-restricted peptide was also significantly stronger by the inclusion of
      LLO in the liposomes. Rerouting of antigen into the cytosol by LLO-liposomes,
      however, did not reduce the extent of anti-OVA antibody responses. Moreover, LLO
      liposome-antigen vaccination was robust in conferring protection to mice from
      lethal challenges with antigen-expressing tumor cells. Our study demonstrates a
      novel delivery system for efficient introduction of exogenous protein into the
      cytosol in vivo, priming cellular immune responses, which are protective in
      nature.

PMID- 12007620
TI  - Mechanisms of calcification by vesicles isolated from atherosclerotic rabbit
      aortas.
AB  - Although several lines of evidence support the role of calcifiable vesicles in
      dystrophic vascular calcification, the mechanisms whereby vesicles promote aortic
      calcification remain incompletely understood. Previous reports indicate that ATP
      promotes in vitro vesicle calcification. Whether ATP-initiated calcification is
      simply mediated through increased Pi concentrations or by other unknown
      mechanisms related to ATP hydrolysis is unclear. To determine whether high Pi
      levels resulting from ATP hydrolysis may cause CaxP ion products to surpass the
      threshold for calcium phosphate precipitation, 3 mM Pi instead of 1 mM ATP was
      added to calcifying media. The inclusion of 1 mM ATP in calcifying media with an
      initial serum level of Ca2+ (1.45 mM) and Pi (2.3 mM) was much more effective in
      promoting calcification than the addition of 3 mM Pi. The higher effectiveness of
      ATP over Pi in promoting calcification was consistent throughout various
      incubation periods and vesicle protein ranges. To minimize the effect of CaxPi
      ion products on calcification, the ion product was kept within the physiological
      ranges throughout the incubation period by reducing initial Pi or ATP
      concentrations in calcifying media. At these low levels of ion products, ATP was
      still more effective than Pi in promoting calcification. Both ATP- and Pi
      stimulated calcifications were found to increase with increasing levels of ion
      products whereas greater effectiveness of ATP over Pi remained unaltered. These
      observations indicate that ATP hydrolysis may initiate calcification through some
      mechanisms other than a simple provision of Pi in order to surpass the solubility
      products. Concanavalin A (Con A) was found to bind to vesicles and to enhance
      both ATP- and Pi-promoted calcification. Taken together, these observations
      suggest that ATP hydrolysis, CaxP ion products, and vesicle-associated
      carbohydrates are implicated in vesicle-mediated calcification.

PMID- 12007621
TI  - Cell synchronization effect on mammalian cell permeabilization and gene delivery
      by electric field.
AB  - Electropermeabilization is a promising nonviral method for gene therapy. However,
      despite the fact that it is widely used to transfer genes into living cells, the
      steps that limit DNA transfer remain to be determined. Here, we report the effect
      of cell synchronization on membrane permeabilization and gene delivery by
      electric fields. Chinese hamster ovary (CHO) cells were synchronized by
      aphidicolin or butyrate treatment. Electro-mediated transfection of these cells
      was evaluated under electric field conditions leading to the same level of
      membrane permeabilization. Aphidicolin cell synchronization in G2/M phase leads
      to a slight increase in plasma membrane permeabilization but to a three-fold
      increase in percentage of transfected cells and to an eight-fold increase in gene
      expression. This increase in cell transfection is specifically due to the G2/M
      synchronization process. Indeed, cell synchronization in G1 phase by sodium
      butyrate has no effect on cell permeabilization and transfection. Our results
      suggest that the enhanced transfection level in G2/M phase is not simply due to
      enhanced permeabilization, but reinforce the statement that the melting of the
      nuclear membrane facilitates direct access of plasmid DNA to the nucleus.

PMID- 12007622
TI  - The effect of hydrostatic pressure on S-layer-supported lipid membranes.
AB  - We report on the behavior of unsupported and surface layer (S-layer)-supported
      lipid membranes at the application of a uniform hydrostatic pressure. At a
      hydrostatic pressure gradient higher than 6 N/m(2), unsupported lipid membranes,
      independent from which side pressurized and S-layer-supported lipid membranes
      pressurized from the lipid-faced side revealed a pronounced increase in
      capacitance. A maximal hydrostatic pressure gradient of 11.0 N/m(2) resulted in
      an almost doubling of the capacitance of the (composite) membranes. S-layer
      supported lipid membranes showed a hysteresis in the capacitance versus pressure
      plot, indicating that this composite structure required a certain time to
      reorient when the pressure gradient acting from the lipid-faced side was
      balanced. By contrast, the S-layer-supported lipid membrane pressurized from the
      protein-faced side revealed only a minute increase in capacitance
      (C/C(0,max)=1.17+/-0.05), reflecting only minor pressure-induced area expansion.
      In addition, no hysteresis could be observed, indicating that no rearrangement of
      the composite membrane occurred. The maximal induced tension was with 4.3+/-0.2
      mN/m, significantly higher than that of unsupported (2.5+/-0.3 mN/m) and S-layer
      supported lipid membranes pressurized from the lipid-faced side (2.6+/-0.1 mN/m).

PMID- 12007623
TI  - Fluorescence probe properties of intramolecular charge transfer
      diphenylbutadienes in micelles and vesicles.
AB  - This paper reports absorption and fluorescence spectral studies of methyl 4
      [(1E,3E)-4-phenylbuta-1,3-dienyl]benzoate (1), N,N-dimethyl-N-[4-[(1E,3E)-4
      phenylbuta-1,3-dienyl]phenyl]amine (2), methyl 4-[(1E,3E)-4-[4
      (dimethylamino)phenyl]buta-1,3-dienyl]benzoate (3) and 1-methyl-4-[(1E,3E)-4-[4
      methoxyphenyl]buta-1,3-dienyl]benzoate (4) in homogeneous media of 1,4-dioxane
      and 1,4-dioxane-water binary mixtures, and in microheterogeneous media of cetyl
      trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS) and Triton-X-100
      micelles, and dipalmotoyl phosphatidylcholine (DPPC) vesicles. The binding site
      of the diene probes in micelles and vesicles has been determined and it has been
      found that while in micelles dienes occupy the polar interfacial regions, in
      vesicles the probes are located deep inside the hydrophobic bilayer. The binding
      of dienes to the vesicles is stronger than their binding to the micelles as
      indicated by the binding constant values. The fluorescence emission of the probe
      dienes in micelles is from a conformationally relaxed intramolecular charge
      transfer excited state. However, in vesicles, since the excited state
      conformational motions are restricted due to the rigidity of the alkyl chain, the
      dienes fluoresce from their planar locally excited states.

PMID- 12007624
TI  - Binding of phosphorothioate oligonucleotides to zwitterionic liposomes.
AB  - Although double-stranded DNA (dsDNA) has been shown to bind to zwitterionic
      lipids, it has been reported that this association is stronger for disordered
      (L(alpha)) phase lipids than for well-ordered (L(beta)) lipids. In this work, the
      interaction of single-strand phosphorothioate oligonucleotides (ONs) with
      unilamellar liposomes of saturated and unsaturated zwitterionic phosphocholines
      (PCs) and phosphoroethylamine (PE) was investigated. It is shown that the
      association of phosphorothioate ONs to diacyl glycerophosphocholines is strong,
      but only for L(beta) phase or otherwise ordered bilayers. There is no measurable
      affinity for PE lipids. The apparent affinity of three different phosphorothioate
      ONs for L(beta) phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) has been
      measured and the dissociation constants were on the order of 10(-7) M. Purine
      rich ON sequences had stronger binding to DPPC liposomes than did pyrimidine-rich
      sequences, but there were other sequence-dependent factors. This exceptionally
      high affinity could be an important consideration in ON uptake, delivery, and
      biodistribution.

PMID- 12007625
TI  - Conformational states of the cell-penetrating peptide penetratin when interacting
      with phospholipid vesicles: effects of surface charge and peptide concentration.
AB  - The most commonly studied of the cell-penetrating peptides (CPP) is "penetratin"
      (pAntp), which functions as a carrier (vector), even for large hydrophilic
      (cargo) molecules. pAntp originates from the third helix of the Antennapedia
      homeodomain protein. The peptide is known to interact with negatively charged
      phospholipid vesicles, which leads to induction of secondary structure. In the
      present study, circular dichroism (CD) spectroscopy has been used to characterize
      the different secondary structures induced upon interaction with small
      unilamellar vesicles (SUVs) from mixtures of zwitterionic 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl
      phosphatidylglycerol (POPG). The interaction was monitored using an electron
      paramagnetic resonance (EPR) spin probe attached to the peptide, and the
      intrinsic fluorophore (tryptophan). We measured the secondary structure as a
      function of surface charge density, total lipid-to-peptide (L/P) molar ratio, and
      salt concentration, for completely bound peptide. With vesicles from POPG/POPC in
      a molar ratio below 30:70, at a high L/P, the peptide adopts a mainly helical
      conformation. Increasing the charge density, at the same L/P, promotes a higher
      degree of beta-structure. At a fixed charge density, reducing the L/P also
      results in an alpha-->beta structure conversion. Hence, low membrane surface
      charge density and low pAntp concentration both favor a mainly helical
      conformation, while high charge density and pAntp concentration promote a
      dominating beta-structure. We conclude that pAntp, when residing at the surface
      of a membrane, is chameleon-like in terms of its induced structure.

PMID- 12007626
TI  - A lipoprotein family from Mycoplasma fermentans confers host immune activation
      through Toll-like receptor 2.
AB  - Mycoplasma have been reported to be associated with human diseases. Three forms
      of a mycoplasma lipopeptide/protein with the ability to modulate the host immune
      system were independently identified and named macrophage-activating lipopeptide
      2 (MALP-2), P48 and M161Ag (identical to MALP-404). Although these molecules had
      polypeptides of different sizes, they exerted similar immunomodulatory effects on
      macrophages/dendritic cells, such as cytokine induction, NO production and
      maturation of antigen-presenting cells (APCs). M161Ag exhibited complement
      activating ability and bound macrophages via complement C3b/C3bi and their
      receptors. The diacylated N-terminal palmitates were involved in these
      activities. Toll-like receptor 2 (TLR2) was found to be responsible for these
      functional features of these mycoplasma products, except for complement
      activation. Here, we summarize the functional properties of this family of
      proteins, namely pathogen-associated molecular pattern (PAMP) and discuss its
      relationship to the reported pathogenesis of latent mycoplasma infection.

PMID- 12007627
TI  - Urocortin.
AB  - Urocortin (Ucn) is a 40 amino acid peptide which is closely related to
      corticotrophin-releasing factor (CRF). It is expressed in specific regions of the
      brain but is also detectable in other organs notably the heart. Although some of
      the effects of Ucn in the nervous system such as enhanced anxiety and activity
      mimic those of CRF, Ucn is a much more potent suppressor of appetite/feeding
      behaviour. Moreover, Ucn has much more potent effects on the cardiovascular
      system than CRF, including enhanced cardiac contractility/heart rate and enhanced
      resistance of cardiac cells to injury induced, for example, by
      ischaemia/reperfusion. This suggests Ucn may play a key role in the response of
      the cardiovascular system to stress. In addition, Ucn represents a novel
      cardioprotective agent which may be of therapeutic use in treating the damaging
      effects of cardiac ischaemia and subsequent reperfusion.

PMID- 12007628
TI  - The acidic ribosomal P proteins.
AB  - The acidic ribosomal P proteins (pI 3-4) are unique among ribosomal constituents:
      the only molecules on the ribosomes existing in multiple copies, they form a
      hetero-oligomeric complex (P1/P2)(2) recognizable as a lateral protuberance on
      the 60S ribosomal subunit, which is thought to be directly involved in
      interactions with elongation factors during the course of protein synthesis. The
      role of P proteins in translation is still vague; however, they might possess two
      functional roles-the proteins may increase performance of ribosomes and/or change
      ribosomal specificity toward different subset of mRNAs. Furthermore, there are
      also indications that P proteins might be involved in transcription and DNA
      repair. Also, P proteins are important antigens in autoimmune diseases,
      infections caused by protozoan parasites, and in molds.

PMID- 12007629
TI  - A novel glutathione transferase from Haemophilus influenzae which has high
      affinity towards antibiotics.
AB  - Cytosolic glutathione transferase (GSTs) are a family of multi-functional
      proteins which catalyse the conjugation of glutathione (GSH) to a large variety
      of endogenous and exogenous electrophilic compounds. Much is known about
      cytosolic mammalian GSTs, however, the presence of GSTs in several aerobic and
      anaerobic micro-organisms has also been demonstrated. Several findings seem to
      suggest that bacterial GSTs are involved in processes of biodegradation of
      xenobiotics, including antibiotics. However, the function played by these enzymes
      in the bacterial cell still remains to be clarified. At present, it is ill
      defined whether bacterial GST can be classified, as in the case of mammalian
      enzymes, into several distinct classes. Here we report the purification of a GST
      isoform from Haemophilus influenzae using GSH-affinity chromatography. The
      purified protein was characterised by immunological and kinetic properties
      different from other known GSTs. The dissociation constants of chloramphenicol,
      ampicillin, rifampicin and tetracycline to the purified enzyme were 0.62, 9.06,
      4.08 and 1.77 microM, respectively, as determined by following the quenching of
      the protein intrinsic fluorescence. These values were much lower than those
      previously determined for the same drugs with other mammalian or bacterial GSTs.
      The present results indicate that the enzyme purified from H. influenzae is a
      novel GST isoform well distinguished from other known mammalian or bacterial
      GSTs.

PMID- 12007630
TI  - Basal and parathyroid hormone induced expression of the human 25-hydroxyvitamin D
      1alpha-hydroxylase gene promoter in kidney AOK-B50 cells: role of Sp1, Ets and
      CCAAT box protein binding sites.
AB  - The regulation of the gene for renal 25-hydroxyvitamin D 1alpha- hydroxylase
      (1alpha(OH)ase; CYP27B1) by parathyroid hormone (PTH) under hypocalcemic
      conditions is fundamentally important for the maintenance of calcium and
      phosphate homeostasis. The molecular mechanism that underlies this hormonal
      response is of current interest and has been investigated in the present study by
      transfection analysis of the human 1alpha(OH)ase promoter in kidney AOK-B50
      cells. We have shown that the first 305 bp of promoter can be induced by hormone
      in transient transfection assays and also within a chromatin environment when
      stably integrated. Mutagenesis of possible transcription factor binding sites
      within this promoter length has shown that three sites clustered within the
      region from -66 to -135 contribute to basal expression. A likely Sp1 and a CCAAT
      box site are particularly important for basal expression although these sites are
      not likely to functionally cooperate in a major way. Mutagenesis of the CCAAT box
      site consistently reduced PTH induction although mutagenesis of the Sp1, Ets and
      other possible binding sites in the 305 bp of promoter has no significant effect
      on the level of PTH induction. Other experiments showed that PTH induction but
      not basal expression was sensitive to the protein kinase inhibitor H89. We have
      therefore identified for the first time the sites in the 1alpha(OH)ase promoter
      responsible for basal expression and provide evidence for the role of a CCAAT box
      binding protein in a PTH mechanism of induction that involves an H89 sensitive
      step.

PMID- 12007631
TI  - Monitoring the kinetics and performance of yeast membrane ABC transporters by diS
      C3(3) fluorescence.
AB  - Kinetic features (initial start-up phase, drug pumping velocity and efficiency as
      dependent on drug concentration and growth phase) of yeast plasma membrane
      multidrug resistance ABC pumps were studied by monitoring the uptake of the
      fluorescent potentiometric dye diS-C3(3), which has been found to be expelled
      from the cells by these pumps. The monitoring was done with Saccharomyces
      cerevisiae mutants AD1-8 and AD1-3 deleted in different ABC pumps, and in their
      pump-competent parent strain US50-18C overexpressing transcriptional activators
      Pdr1p and Pdr3p. On addition to the cells, diS-C3(3) is expelled by the Pdr5p,
      Yor1p and Snq2p pumps with overlapping substrate specificity. The pump action can
      be assessed as a difference between the dye uptake curve for pump-competent and
      pump-deleted cells. The pump-mediated dye efflux, which shows an initial lag of
      various lengths, maintains a certain residual intracellular dye level. In the
      absence of external glucose the dye efflux ability of the pumps depends on the
      growth phase; late exponential and stationary cells can maintain the export for
      tens of minutes, whereas exponential cells keep up the pump action for limited
      time periods. This may reflect an insufficient number of pump molecules in the
      membrane or an effect of insufficient pump energization from endogenous sources.
      This effect is not mediated by changes in membrane potential because lowered
      membrane potential caused by inhibition of the plasma membrane H+-ATPase does not
      affect the pump action.

PMID- 12007632
TI  - Differential changes in protein kinase C associated with regeneration of rat
      extensor digitorum longus and soleus muscles.
AB  - We used a model of crush-induced regeneration in rat in order to characterize
      biochemically and histologically the implication of protein kinase C (PKC) in
      muscle repair after damage. In this model, slow soleus and fast extensor
      digitorum longus (EDL) muscle regeneration proceed differently. PKC activity has
      been assayed in regenerating muscles and their intact contralateral during the
      first 14 days following crushing. Degeneration (myolysis) occurring shortly after
      crush was associated with a marked down-regulation of the enzyme in both wound
      muscles and notable increase in the corresponding contralateral muscles. Muscle
      fiber reconstruction in EDL was associated with a rise in PKC activity which
      peaked at day 7 in regenerating muscle where it was twice higher than in intact
      muscle. At variance, muscle PKC activity in soleus increased slower than that of
      EDL and reached later intact level. Western blot analysis and immunohistochemical
      studies of representative members of the three PKC subfamilies were performed.
      All the isoform tested were much less expressed in regenerating than in control
      intact muscles suggesting that the overall PKC activity in regenerating muscles
      was more activable than in controls. We have shown that PKC isoforms were
      sequentially expressed during regeneration in both muscle types. PKC theta; being
      present the earliest, then delta, epsilon and alpha and finally zeta, beta and
      eta. Some isoforms were differentially expressed according muscle type. PKC delta
      being more expressed in soleus whereas beta and eta appeared earlier in EDL.
      Histochemical studies have revealed that the isoforms were differently localized
      in muscle tissue and that fiber regeneration was associated with PKC alpha
      translocation from sarcoplasma to sarcolemma. Together these data have shown that
      multiple PKC isoforms are implicated in the regenerative process acting at
      different in times and location and suggesting that individual isoform may
      fulfill distinct functions.

PMID- 12007633
TI  - Changes in BRCA1 and BRCA2 expression produced by chemotherapeutic agents in
      human breast cancer cells.
AB  - We have investigated the effects of chemotherapeutic agents such as adriamycin
      (ADR), camptothecin (CPT), mitomycin-C (MYC-C) and methotrexate (MTX) on the
      regulation of expression of the tumor susceptibility genes (BRCA1 and BRCA2), and
      the association of cell cycle progression in human breast cancer and normal
      breast epithelial cells. Results revealed that the mRNA and protein expression
      levels of BRCA1/2 were reduced by the treatment of chemotherapeutic agents used
      in the breast cancer cell lines tested, with ADR being the most effective. The
      regulation of the cell cycle was dose-dependent and low doses of ADR (1.5 microM)
      induced G2/M phase arrest whereas a late S phase arrest was observed with a
      higher dose of ADR (15 microM) in both breast cancer cells (MCF-7 and MDA-MB-231)
      tested. In addition, a negative correlation was observed between BRCA1/2 mRNA and
      expressions of the proteins with the cell cycle alterations being regulated by
      chemotherapeutic agents.

PMID- 12007634
TI  - Isolation and characterisation of a novel rabbit sulfotransferase isoform
      belonging to the SULT1A subfamily.
AB  - Sulfotransferases (SULTs) catalyse the sulfonation of both endogenous and
      exogenous compounds including hormones, catecholamines, drugs and xenobiotics.
      While in most occasions, sulfonation is a detoxication pathway, in the case of
      certain drugs and carcinogens, it leads to metabolic activation. Since, the
      rabbit has been extensively used for both pharmacological and toxicological
      studies, the purpose of this study was to further characterise the
      sulfotransferase system of this animal. In the present study, a novel
      sulfotransferase isoform (GenBank Accession no. AF360872) was isolated from a
      rabbit liver cDNA lambdaZAP II library. The full-length sequence of the clone was
      1138 bp long and contained a coding region of 888 bp encoding a cytosolic protein
      of 295 amino acids (deduced molecular weight 34,193 Da). The amino acid sequence
      of this novel SULT isoform showed >70% identity with members of the SULT1A
      subfamily of sulfotransferases from other species. Upon expression of the encoded
      rabbit sulfotransferase in Escherchia coli (E. coli), it was shown that the
      enzyme was capable of sulfonating both p-nitrophenol (K(m) and Vmax values of
      0.15 microM and 897.5 nmol/min/mg protein, respectively) and dopamine (K(m) and
      V(max) values of 175.3 microM and 151.1 nmol/min/mg protein, respectively). Based
      on the sequence data obtained and substrate specificity, this new rabbit
      sulfotransferase was named rabSULT1A1. Immunoblotting was used to demonstrate
      that rabSULT1A1 protein is expressed in liver, duodenum, jejunum, ileum, colon
      and rectum.

PMID- 12007635
TI  - Effects of aspartate on rabbit muscle creatine kinase and the salt induced molten
      globule state.
AB  - The aspartate (Asp)-induced unfolding and the salt-induced folding of creatine
      kinase (CK) have been studied by measuring enzyme activity, fluorescence emission
      spectra, circular dichroism (CD) spectra, native polyacrylamide gel
      electrophoresis and ultraviolet difference spectra. The results showed that Asp
      caused inactivation and unfolding of CK, with no aggregation during CK
      denaturation. The kinetics of CK unfolding followed a one phase process. At
      higher concentrations of Asp (>2.5mM), the CK dimers were partially dissociated.
      Inactivation occurred before noticeable conformational change during CK
      denaturation. Asp denatured CK was mostly reactivated and refolded by dilution.
      KCl induced the molten globule state with compact structure after CK was
      denatured with 10mM Asp. These results suggest that the effect of Asp differed
      from that of other denaturants such as guanidine, HCl or urea during CK
      unfolding. Asp is a reversible protein denaturant and the molten globule state
      indicates that intermediates exist during CK folding.

PMID- 12007636
TI  - Effects of removal of the N-terminal amino acid residues on the activity and
      conformation of firefly luciferase.
AB  - A series of deletion mutants were constructed using polymerase chain reaction
      (PCR) to investigate the roles of luciferase N-terminal residues. The coding
      sequences of the first 0 (Luc0), 6 (Luc6), 7 (Luc7), 8 (Luc8), 9 (Luc9), 10
      (Luc10) and 20 (Luc20) amino acids of the N-terminus were deleted and inserted
      into the prokaryotic expression vector pBV220. The results showed that the
      enzymes were completely inactivated when the first eight or more N-terminal amino
      acids were removed. The recombinant Luc0 and mutants Luc6 and Luc7 were purified
      to homogeneity by ammonium sulfate precipitation and liquid chromatography for
      determination of their activity and conformational changes. The activity assay
      showed that removal of the first six amino acids resulted in 29% loss of
      enzymatic activity while removal of the first seven amino acids resulted in
      nearly complete inactivation (with remaining activity <0.5% of the original
      activity). Circular dichroism spectra showed no significant secondary structure
      changes. But the fluorescence emission maximum red-shift indicated some
      conformational changes. Luc6 and Luc7 were more sensitive to guanidine unfolding
      than Luc0. The present result indicated the significant role of Ile7 to the
      luciferase stability.

PMID- 12007637
TI  - Calcium modulates the ATP and ADP hydrolysis in human placental mitochondria.
AB  - This study evaluated the effect of Ca2+ on the extramitochondrial hydrolysis of
      ATP and ADP by the extramitochondrial ATPase in isolated mitochondria and
      submitochondrial particles (SMPs) from human term placenta. The effect of
      different oxidizable substrates on the hydrolysis of ATP and ADP in the presence
      of sucrose or K+ was evaluated. Ca2+ increased phosphate release from ATP and
      ADP, but this stimulation showed different behavior depending on the oxidizable
      substrate present in the incubation media. Ca2+ stimulated the hydrolysis of ATP
      and ADP in the presence of sucrose. However, Ca2+ did not stimulate the
      hydrolysis of ADP in the medium containing K+. Ca2+ showed inhibition depending
      on the respiratory substrate. This study suggests that the energetic state of
      mitochondria controls the extramitochondrial ATPase activity, which is modulated
      by Ca2+ and respiratory substrates.

PMID- 12007638
TI  - Differential effects of magnesium on the hydrolysis of ADP and ATP in human term
      placenta. Effect of substrates and potassium.
AB  - This study evaluates the effect of Mg2+ on the extramitochondrial hydrolysis of
      ATP and ADP by human term placental mitochondria (HPM) and submitochondrial
      particle (SMP). Extramitochondrial ATPase and ADPase activities were evaluated in
      the presence or absence of K+, and different oxidizable substrates. Mg2+
      increased both ATP and ADP hydrolysis according to the experimental conditions,
      and this stimulation was related to the mitochondrial intactness. The ADPase
      activity in intact mitochondria is 100-fold higher in presence of K+, succinate
      and 1mM Mg2+ while this activity is only increased by two-fold on the SMP when
      compared to the sample without Mg2+. It is clearly demonstrated that up
      regulation of these enzyme activities occur in intact mitochondria and not on the
      enzyme itself. The results suggest that the regulation of ATP and ADP hydrolysis
      is complex, and Mg2+ plays an important role in the modulation of the
      extramitochondrial ATPase and ADPase activities in HPM

PMID- 12007639
TI  - PAV-1, a new rat hepatic stellate cell line converts retinol into retinoic acid,
      a process altered by ethanol.
AB  - During liver fibrogenesis or long term culture, hepatic stellate cells (HSCs)
      evolved from "quiescent" to activated phenotype called "myofibroblast-like", a
      transition prevented by retinoic acid (RA). Little is known about RA generation
      by HSCs. Our study aimed to check the ability of these cells to produce RA from
      retinol (Rol) and the alterations of this metabolic step by ethanol. To study
      this metabolic pathway, primary cultures of HSCs represent the most physiological
      model but technically suffer several drawbacks. To circumvent these problems, an
      immortalized rat HSC line (named PAV-1) has been established. We validated PAV-1
      cell line as a convenient model to study retinoids metabolism by HSCs. Then, we
      showed that PAV-1 cells express Rol-binding proteins (RBPs), enzymes and nuclear
      receptors involved in RA signaling pathway. We also demonstrated in situ
      generation of functional all-trans-RA (ATRA), using transient transfections with
      a RA-sensitive reporter gene, in situ modulation of tissue transglutaminase (tTG)
      activity and HPLC experiments. This production was Rol dose-dependent; 4
      methylpyrazole, citral, and ethanol-inhibited which argues in favor of an
      enzymatic process.In conclusion, we first demonstrate in situ RA generation from
      Rol in a newly immortalized rat HSC line, named PAV-1. Inhibition of RA
      production by ethanol in PAV-1 and recent data, suggesting fundamental role of RA
      to prevent fibrosis development in the liver, allow us to hypothesize that Rol
      metabolism could be a primary target for ethanol during development of hepatic
      fibrosis.

PMID- 12007640
TI  - Fluoroquinolone resistance in Salmonella serovars isolated from humans and food
      animals.
AB  - Quinolone-resistant Salmonella enterica usually contain a mutation in gyrA within
      the region encoding the quinolone resistance determining region of the A subunit
      of DNA gyrase. These mutations confer substitutions analogous to Escherichia coli
      Ser83-->Phe and Asp87-->Gly or Tyr, or a novel mutation resulting in Ala119-->Glu
      or Val. Mutations in gyrB are rare, and no mutations in parC or parE have been
      described. Quinolone-resistant Salmonella can also be cross-resistant to other
      agents including chloramphenicol and tetracycline. Increased efflux has been
      demonstrated and for some strains this has been associated with increased
      expression of acrB. Mutation in soxR has also been shown for one isolate.
      Detection of low level resistance (minimum inhibitory concentrations <0.5 microg
      ml(-1)) to fluoroquinolones is proving an increasing problem in the treatment of
      invasive Salmonella infections.

PMID- 12007641
TI  - O-antigen structural variation: mechanisms and possible roles in animal/plant
      microbe interactions.
AB  - Current data from bacterial pathogens of animals and from bacterial symbionts of
      plants support some of the more general proposed functions for
      lipopolysaccharides (LPS) and underline the importance of LPS structural
      versatility and adaptability. Most of the structural heterogeneity of LPS
      molecules is found in the O-antigen polysaccharide. In this review, the role and
      mechanisms of this striking flexibility in molecular structure of the O-antigen
      in bacterial pathogens and symbionts are illustrated by some recent findings. The
      variation in O-antigen that gives rise to an enormous structural diversity of O
      antigens lies in the sugar composition and the linkages between monosaccharides.
      The chemical composition and structure of the O-antigen is strain-specific
      (interstrain LPS heterogeneity) but can also vary within one bacterial strain
      (intrastrain LPS heterogeneity). Both LPS heterogeneities can be achieved through
      variations at different levels. First of all, O-polysaccharides can be modified
      non-stoichiometrically with sugar moieties, such as glucosyl and fucosyl
      residues. The addition of non-carbohydrate substituents, i.e. acetyl or methyl
      groups, to the O-antigen can also occur with regularity, but in most cases these
      modifications are again non-stoichiometric. Understanding LPS structural
      variation in bacterial pathogens is important because several studies have
      indicated that the composition or size of the O-antigen might be a reliable
      indicator of virulence potential and that these important features often differ
      within the same bacterial strain. In general, O-antigen modifications seem to
      play an important role at several (at least two) stages of the infection process,
      including the colonization (adherence) step and the ability to bypass or overcome
      host defense mechanisms. There are many reports of modifications of O-antigen in
      bacterial pathogens, resulting either from altered gene expression, from
      lysogenic conversion or from lateral gene transfer followed by recombination. In
      most cases, the mechanisms underlying these changes have not been resolved.
      However, in recent studies some progress in understanding has been made. Changes
      in O-antigen structure mediated by lateral gene transfer, O-antigen conversion
      and phase variation, including fucosylation, glucosylation, acetylation and
      changes in O-antigen size, will be discussed. In addition to the observed LPS
      heterogeneity in bacterial pathogens, the structure of LPS is also altered in
      bacterial symbionts in response to signals from the plant during symbiosis. It
      appears to be part of a molecular communication between bacterium and host plant.
      Experiments ex planta suggest that the bacterium in the rhizosphere prepares its
      LPS for its roles in symbiosis by refining the LPS structure in response to seed
      and root compounds and the lower pH at the root surface. Moreover, modifications
      in LPS induced by conditions associated with infection are another indication
      that specific structures are important. Also during the differentiation from
      bacterium to bacteroid, the LPS of Rhizobium undergoes changes in the composition
      of the O-antigen, presumably in response to the change of environment. Recent
      findings suggest that, during symbiotic bacteroid development, reduced oxygen
      tension induces structural modifications in LPS that cause a switch from
      predominantly hydrophilic to predominantly hydrophobic molecular forms. However,
      the genetic mechanisms by which the LPS epitope changes are regulated remain
      unclear. Finally, the possible roles of O-antigen variations in symbiosis will be
      discussed.

PMID- 12007642
TI  - Bacterial osmoadaptation: the role of osmolytes in bacterial stress and
      virulence.
AB  - Two general strategies exist for the growth and survival of prokaryotes in
      environments of elevated osmolarity. The 'salt in cytoplasm' approach, which
      requires extensive structural modifications, is restricted mainly to members of
      the Halobacteriaceae. All other species have convergently evolved to cope with
      environments of elevated osmolarity by the accumulation of a restricted range of
      low molecular mass molecules, termed compatible solutes owing to their
      compatibility with cellular processes at high internal concentrations. Herein we
      review the molecular mechanisms governing the accumulation of these compounds,
      both in Gram-positive and Gram-negative bacteria, focusing specifically on the
      regulation of their transport/synthesis systems and the ability of these systems
      to sense and respond to changes in the osmolarity of the extracellular
      environment. Finally, we examine the current knowledge on the role of these
      osmostress responsive systems in contributing to the virulence potential of a
      number of pathogenic bacteria.

PMID- 12007643
TI  - Microbial carboxyl esterases: classification, properties and application in
      biocatalysis.
AB  - Esterases (EC 3.1.1.x) represent a diverse group of hydrolases catalyzing the
      cleavage and formation of ester bonds and are widely distributed in animals,
      plants and microorganisms. Beside lipases, a considerable number of microbial
      carboxyl esterases have also been discovered and overexpressed. This review
      summarizes their properties and classification. Special emphasis is given on
      their application in organic synthesis for the resolution of racemates and
      prostereogenic compounds. In addition, recent results for altering their
      properties by directed evolution are presented.

PMID- 12007644
TI  - The hexokinase 2-dependent glucose signal transduction pathway of Saccharomyces
      cerevisiae.
AB  - Sugars, predominantly glucose, evoke a variety of responses in Saccharomyces
      cerevisiae. These responses are elicited through a complex network of regulatory
      mechanisms that transduce the signal of presence of external glucose to their
      final intracellular targets. The HXK2 gene, encoding hexokinase 2 (Hxk2), the
      enzyme that initiates glucose metabolism, is highly expressed during growth in
      glucose and plays a pivotal role in the control of the expression of numerous
      genes, including itself. The mechanism of this autocontrol of expression is not
      completely understood. Hxk2 is found both in the nucleus and in the cytoplasm of
      S. cerevisiae; the nuclear localization is dependent on the presence of a stretch
      of amino acids located from lysine-6 to methionine-15. Although serine-14, within
      this stretch, can be phosphorylated in the absence of glucose, it is still
      unsettled whether this phosphorylation plays a role in the cellular localization
      of Hxk2. The elucidation of the mechanism of transport of Hxk2 to and from the
      nucleus, the influence of the oligomeric state of the protein on the nuclear
      transport and the fine mechanism of regulation of transcription of HXK2 are among
      the important unanswered questions in relation with the regulatory role of Hxk2.

PMID- 12007645
TI  - An overview of the evolution of enterovirus 71 and its clinical and public health
      significance.
AB  - Since its discovery in 1969, enterovirus 71 (EV71) has been recognised as a
      frequent cause of epidemics of hand-foot-and-mouth disease (HFMD) associated with
      severe neurological sequelae in a small proportion of cases. There has been a
      significant increase in EV71 epidemic activity throughout the Asia-Pacific region
      since 1997. Recent HFMD epidemics in this region have been associated with a
      severe form of brainstem encephalitis associated with pulmonary oedema and high
      case-fatality rates. The emergence of large-scale epidemic activity in the Asia
      Pacific region has been associated with the circulation of three genetic lineages
      that appear to be undergoing rapid evolutionary change. Two of these lineages (B3
      and B4) have not been described previously and appear to have arisen from an
      endemic focus in equatorial Asia, which has served as a source of virus for HFMD
      epidemics in Malaysia, Singapore and Australia. The third lineage (C2) has
      previously been identified [Brown, B.A. et al. (1999) J. Virol. 73, 9969-9975]
      and was primarily responsible for the large HFMD epidemic in Taiwan during 1998.
      As EV71 appears not to be susceptible to newly developed antiviral agents and a
      vaccine is not currently available, control of EV71 epidemics through high-level
      surveillance and public health intervention needs to be maintained and extended
      throughout the Asia-Pacific region. Future research should focus on (1)
      understanding the molecular genetics of EV71 virulence, (2) identification of the
      receptor(s) for EV71, (3) development of antiviral agents to ameliorate the
      severity of neurological disease and (4) vaccine development to control
      epidemics. Following the successful experience of the poliomyelitis control
      programme, it may be possible to control EV71 epidemics if an effective live
      attenuated vaccine is developed.

PMID- 12007646
TI  - Type 1 and type 2 responses to Leishmania major.
AB  - Leishmania major is a protozoan parasite that is transmitted to the mammalian
      host by its sand fly vector when the fly probes in the host's skin for a blood
      meal and injects the parasite within its saliva. In mice experimentally infected
      with L. major, outgrowth of CD4 type 1 (Th1) cells leads to resolution of the
      infection, but outgrowth of type 2 (Th2) cells exacerbates disease. To design an
      effective vaccine against the parasite (and other pathogens that induce polarized
      Th1 and Th2 responses), we must determine the mechanism underlying this
      phenomenon so that we can design the vaccine to elicit the appropriate (i.e.,
      protective) Th cell. Recent work indicates that Th bias is influenced by a number
      of signals delivered by antigen-presenting cells, including cytokines and co
      stimulatory molecules. Moreover, recent work also suggests that sand fly saliva
      influences the immune response to L. major and Th polarization. Determining the
      mechanisms that lead to polarized Th responses should expand our knowledge
      regarding immunity to L. major, and should add to our understanding of
      immunoregulation in general.

PMID- 12007647
TI  - Osmolarity hypersensitivity of hog1 deleted mutants is suppressed by mutation in
      KSS1 in budding yeast Saccharomyces cerevisiae.
AB  - An osmosensing mechanism of Saccharomyces cerevisiae involves a mitogen-activated
      protein kinase (MAPK) cascade (HOG pathway). This study aimed to investigate the
      response of the yeast to osmotic stress. A mutant strain, in which the HOG1 gene
      was disrupted by TRP1, was constructed. A spontaneous mutant, named YJY45, which
      suppresses the osmosensitive growth phenotype of the hog1 deletion mutant, was
      selected and showed a secondary phenotype of temperature sensitivity on YPD
      containing 0.5 M NaCl at 37 degrees C. Our data indicate that the spontaneous
      mutation in YJY45 mutant was mapped in KSS1, which is one of the MAPK family. The
      mutation in KSS1 suppresses the osmolarity-hypersensitive phenotype of the hog1
      deletion mutation and restores GPD1 induction.

PMID- 12007648
TI  - Effects of porphyrins and inorganic iron on the growth of Prevotella intermedia.
AB  - We demonstrated earlier that hemin-iron-containing compounds which include hemin,
      human hemoglobin, bovine hemoglobin, and bovine catalase stimulate the growth of
      Prevotella intermedia [Leung, Subramaniam, Okamoto, Fukushima, Lai, FEMS
      Microbiol. Lett. 162 (1998) 227-233]. However, the contributions of tetrapyrrole
      porphyrin ring in these hemin-iron sources as well as inorganic iron for the
      growth of this organism have not been determined. The purpose of this study was
      to examine the effects of porphyrins, host iron-binding proteins, and various
      inorganic iron sources on the growth of hemin-iron depleted P. intermedia.
      Protoporphyrin IX and protoporphyrin IX-zinc, either in the presence or absence
      of supplemented ferrous or ferric iron, promoted the growth of P. intermedia at a
      rate that was comparable to that of the hemin control. On the other hand, neither
      the host iron proteins, transferrin and lactoferrin, nor the inorganic iron
      sources which included ferrous chloride, ferric chloride, ferric citrate, ferric
      nitrate, and ferric ammonium citrate at concentrations up to 200 microM
      stimulated the growth of hemin-iron-restricted P. intermedia. The results suggest
      that P. intermedia only use iron in a specific form and that the porphyrin-ring
      structure is essential for the growth of P. intermedia as in the case of other
      related organisms.

PMID- 12007649
TI  - Co-linear scaffold of the Bacillus licheniformis and Bacillus subtilis genomes
      and its use to compare their competence genes.
AB  - We have established the co-linear regions of Bacillus licheniformis, an
      industrially important bacterium, and Bacillus subtilis, a model bacterium. In
      the co-linear regions, revealed by PCR, gene content and order are presumed to be
      conserved. These regions constitute approximately 60% of the compared
      chromosomes. Sequencing of the competence genes of B. licheniformis allowed us to
      validate the approach, and to demonstrate how it can be used for the comparative
      analysis of complex genetic systems. A new insertion sequence, designated
      IS3Bli1, was discovered in the competence region of the analyzed B. licheniformis
      strain.

PMID- 12007650
TI  - Purification and characterization of a putative virulence factor, serine
      protease, from Vibrio parahaemolyticus.
AB  - A protease (protease A) was successfully purified from the extracellular proteins
      of Vibrio parahaemolyticus no. 93, a clinical strain carrying neither tdh nor trh
      genes, using phenyl-Sepharose CL-4B hydrophobic interaction chromatography. The
      molecular mass of protease A was 43 kDa using gel filtration, which was in
      agreement with the results obtained from SDS-PAGE, suggesting that protease A was
      a monomeric protein. Additionally, the isoelectric point of this protein was 5.0.
      The optimum temperature and pH of protease A ranged from 40 degrees C to 50
      degrees C and pH 8, respectively. Protease A activity was inhibited by serine
      protease inhibitors, such as phenylmethylsulfonyl fluoride and soybean trypsin
      inhibitor; moreover, the activity could be blocked by treatment with 20 mM of
      1,10-phenanthroline, but could not be restored by adding metal ions. These
      results indicated that protease A is a serine protease that requires metal. The
      12 N-terminal residues of protease A showed a high degree of identity (81%) to
      the sequence of Vibrio metschnikovii VapT serine protease. The purified protease
      had significant effects on the growth of Chinese hamster ovary, HeLa, Vero and
      Caco-2 cells and its cytotoxic activity was not blocked by gangliosides. Protease
      A lysed erythrocytes well but its hemolytic activity was unstable after heat
      treatment, indicating that protease A is able to cause hemolysis but is a heat
      labile protein. The purified protease caused tissue hemorrhage and death in mice
      when injected both intraperitoneally and intravenously. In conclusion, this is
      the first report of a serine protease purified directly from the supernatant of
      V. parahaemolyticus and identifying it as a potential virulence factor.

PMID- 12007651
TI  - Role of the glutamic and aspartic residues in Na+-ATPase function in the ZrENA1
      gene of Zygosaccharomyces rouxii.
AB  - The effect of replacement of negatively charged amino acid residues on the
      function of Na+ transport proteins of the salt-tolerant yeast Zygosaccharomyces
      rouxii was examined by heterologous expression of mutant proteins in a strain of
      Saccharomyces cerevisiae, RH16.6, that lacks native Na+-ATPase activity due to
      null mutations of ENA1, ENA2, ENA3, and ENA4. Mutants of Na+/H+ antiporter gene
      (ZrSOD2) and Na+-ATPase gene (ZrENA1) of Z. rouxii were generated by site
      directed mutagenesis. The significance of two aspartic residues arranged in
      tandem (D265 and D266) was demonstrated in Z. rouxii Na+/H+ antiporter. Some Z.
      rouxii Na+-ATPase mutant genes, namely E778A, D852A, and E981A present in the
      transmembrane domains (TMDs) and D736A, D743A, D748A, D749A, D759A, and D760A
      present in the cytoplasmic space were constructed. A lower level of salt
      tolerance was bestowed by the mutant genes D852A and E981A present in TMDs and
      D748A and D749A present in cytoplasmic space, compared with the wild-type gene
      (ZrENA1).

PMID- 12007652
TI  - Helicobacter muricola sp. nov., a novel Helicobacter species isolated from the
      ceca and feces of Korean wild mouse (Mus musculus molossinus).
AB  - A slowly growing microaerophilic Helicobacter strain was isolated from the ceca
      and fecal pellets of Korean wild mice (Mus musculus molossinus). This bacterial
      strain possessed a pair of nonsheathed bipolar flagella, was positive for urease,
      catalase and oxidase, and reduced nitrate to nitrite. It proved susceptible to
      nalidixic acid and resistant to cephalodine, and did not hydrolyze hippurate. On
      the basis of phenotypic characteristics and 16S rRNA gene sequence analysis, the
      isolate represents a new species of the genus Helicobacter, for which the name
      Helicobacter muricola sp. nov. is proposed; the type strain of the new species is
      w-06T.

PMID- 12007653
TI  - Evaluation of N-acetylchitooligosaccharides as the main carbon sources for the
      growth of intestinal bacteria.
AB  - N-Acetylchitooligosaccharides ((GlcNAc)(n)) with different degrees of
      polymerization (n=1-6) were prepared as the main carbon sources in media for
      evaluating the growth of nine intestinal bacteria. A chitohydrolysate was
      prepared by hydrolyzing shrimp-shell chitin using HCl. After purification, the
      purity of each (GlcNAc)(1-6) was >86%. The growth of intestinal bacteria was
      carried out in a basal medium (BM) containing 0.2% (w/v) of each sugar or glucose
      as the main carbon source and was evaluated using maximum cell densities and
      specific growth rates. Bacteroides fragilis and Clostridium perfringens could
      respectively utilize GlcNAc and (GlcNAc)(2) more efficiently for growth than
      glucose. Bifidobacterium adolescentis and Eubacterium limosum could use
      (GlcNAc)(1-6) slightly as their main carbon source. Escherichia coli, Lactococcus
      lactis and Proteus vulgaris could utilize glucose more efficiently than
      (GlcNac)(1-6). GlcNAc was used more readily than (GlcNAc)(2-6) by Staphylococcus
      aureus, exhibiting almost the same specific growth rates. In BM, Streptococcus
      faecalis grew well even without adding each of the sugars tested.

PMID- 12007654
TI  - Isolation and characterisation of 8-hydroxy-3Z,5Z-tetradecadienoic acid, a
      putative intermediate in Pichia guilliermondii gamma-decalactone biosynthesis
      from ricinoleic acid.
AB  - During a screening procedure for the discovery of a strong gamma-decalactone
      producer from ricinoleic acid, we observed that the yeast Pichia guilliermondii
      accumulated transiently 8-hydroxy-3Z,5Z-tetradecadienoic acid 1 during gamma
      decalactone biosynthesis in the stationary phase of growth. The structural
      elucidation of 1 was based on nuclear magnetic resonance, infrared, ultraviolet
      and gas chromatography-mass spectrometry experiments. The occurrence of 1 is
      discussed in relation with previously proposed gamma-decalactone biosynthetic
      pathways.

PMID- 12007655
TI  - Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects.
AB  - Polysaccharides were extracted from fruiting bodies and cultured mycelia from
      five Antrodia camphorata strains. Polysaccharide profiles of the five strains, as
      determined by high-performance anion-exchange chromatography, showed varying
      yields and composition of neutral sugars. A. camphorata fruiting bodies also had
      different polysaccharide patterns compared to the cultured mycelium. Analysis of
      26-day-old mycelia showed that the neutral sugars galactose, glucose, mannose,
      and galactosamine were predominant. All mycelia polysaccharide preparations
      exhibited anti-hepatitis B virus activity. Polysaccharides from strain B86 at a
      concentration of 50 microg ml(-1) showed the highest level of anti-hepatitis B
      surface antigen effect, which was higher than alpha-interferon at a dosage of
      1000 U ml(-1). Only strains B86 and 35398 had substantial anti-hepatitis B e
      antigen activities. None of the polysaccharides exhibited cytotoxic effects.

PMID- 12007656
TI  - Characterisation of the diol dehydratase pdu operon of Lactobacillus collinoides.
AB  - The three genes (pduCDE) encoding the diol dehydratase of Lactobacillus
      collinoides were sequenced. They exhibited strong identities with the ddrABC and
      pduCDE genes of Klebsiella oxytoca and Salmonella enterica, respectively. These
      genes are part of a putative operon with at least four other genes. An eighth
      open reading frame was identified as homologous to the pocR gene (encoding the
      operon regulatory protein). Although the enzyme was detected in exponential
      growth phase, PduCDE activity was increased at the end of exponential phase in
      presence of 1,2-propanediol.

PMID- 12007657
TI  - Pathways for lactose/galactose catabolism by Streptococcus salivarius.
AB  - Galactokinase and beta-galactosidase-deficient strains of Streptococcus
      salivarius were constructed to define the pathways for lactose and galactose
      catabolism. It was found that S. salivarius does not possess a lactose-specific
      phosphoenolpyruvate phosphotransferase system (PTS), that intracellular lactose
      was hydrolyzed by beta-galactosidase, and that galactose is catabolized
      exclusively through the Leloir pathway. The lack of a high-affinity PTS for
      lactose may reflect the higher availability of the substrates to soft tissue
      organisms, such as S. salivarius, compared to dental plaque bacteria.

PMID- 12007658
TI  - Identification of a CysB-regulated gene involved in glutathione transport in
      Escherichia coli.
AB  - Growth of Escherichia coli using the tripeptide glutathione as a sulfur source is
      well documented, but transport of glutathione into E. coli is uncharacterized. We
      have found that the ybiK gene, at 18.7 min, appears to be involved in the
      transport of glutathione and have therefore renamed ybiK as spt for sulfur
      peptide transport. The ybiK/spt gene is the first of what appear to be five
      cotranscribed genes, three of which show high homology to the peptide transport
      operon dpp. When the lacZ gene encoding beta-galactosidase was fused to the
      promoter of ybiK/spt, expression of the ybiK-lacZ fusion was repressed in rich
      media. This was shown to be due to the presence of exogenous cysteine. The ybiK
      lacZ fusion was found to be regulated by cysB, the transcriptional activator for
      the cysteine regulon. Mutations in the cysB or ybiK genes led to severe growth
      inhibition when cells were given glutathione as the sole sulfur source. In
      particular, strains of E. coli containing mutations in both the ybiK and cysA
      genes were unable to grow when the sole sulfur source provided was glutathione
      whereas single cysA mutants grew well with glutathione. In contrast, no such
      defects were seen when L-djenkolic acid or cysteine were used as the sole sulfur
      source.

PMID- 12007659
TI  - A novel gene encoding amidinotransferase in the cylindrospermopsin producing
      cyanobacterium Aphanizomenon ovalisporum.
AB  - The hepatotoxin cylindrospermopsin is produced by several cyanobacteria species,
      which may flourish in tropical and sub-tropical lakes. Biosynthesis of
      cylindrospermopsin is poorly understood but its chemical nature, and feeding
      experiments with stable isotopes, suggested that guanidinoacetic acid is the
      starter unit and indicated involvement of a polyketide synthase. We have
      identified a gene encoding an amidinotransferase from the cylindrospermopsin
      producing cyanobacterium Aphanizomenon ovalisporum. This is the first report on
      an amidinotransferase gene in cyanobacteria. It is likely to be involved in the
      formation of guanidinoacetic acid. The aoaA is located in a genomic region
      bearing genes encoding a polyketide synthase and a peptide synthetase, further
      supporting its putative role in cylindrospermopsin biosynthesis.

PMID- 12007660
TI  - The adaptation and resistance of Clostridium aminophilum F to the butyrivibriocin
      like substance of Butyrivibrio fibrisolvens JL5 and monensin.
AB  - When the amino acid-fermenting bacterium Clostridium aminophilum F was inoculated
      into media containing 1 microM monensin or a bacteriocin-like inhibitory
      substance (BLIS) from Butyrivibrio fibrisolvens JL5, the cultures lagged and
      growth was not observed for more than 12 h. The monensin- and BLIS-treated
      cultures eventually grew rapidly and did not lag a second time. Because cross
      resistance could not be demonstrated, it appeared that the adaptation was
      specific. Non-adapted cells that were incubated with monensin lost their ability
      to produce ammonia from amino acids, and ATP, intracellular potassium, and
      electrical potential (DeltaPsi) were lower than untreated cells. Monensin-adapted
      cells regained their ability to produce ammonia, and intracellular potassium and
      DeltaPsi increased, but ATP was still 40% lower than untreated cells. When non
      adapted cells were treated with the BLIS, ammonia production did not decline. Non
      adapted cells were agglutinated by lysozyme, but in each case, adapted cells were
      not agglutinated. Adapted cells had more cellular polysaccharide and bound less
      of either inhibitor. Based on these results, it appears that the adapted cells
      had altered cell wall characteristics that prevented the binding of either
      monensin or the B. fibrisolvens JL5 BLIS.

PMID- 12007661
TI  - Microbiological characterisation of Burkholderia cepacia isolates from cystic
      fibrosis patients: investigation of the exopolysaccharides produced.
AB  - Eleven strains of Burkholderia cepacia were isolated directly from clinical
      specimens: 10 from sputum of cystic fibrosis patients, and one from a vaginal
      swab. They were biochemically identified using API20NE and confirmed by a PCR
      based assay. The genomovar characterisation obtained by specific PCR
      amplification revealed seven strains belonging to genomovar I, three belonging to
      genomovar IIIA and one belonging to genomovar IV. All isolates were also typed by
      ribotyping and random amplification of polymorphic DNA analysis. Some of the
      characterised strains were examined for the ability to produce
      exopolysaccharides, with the aim of correlating the genomovar with the
      exopolysaccharide structure. The polysaccharides were analysed by means of
      methylation analysis and 1H-NMR spectroscopy in order to determine structural
      similarities. It was shown that different strains are capable of producing
      chemically different polysaccharides.

PMID- 12007662
TI  - Use of NIR and pyrolysis-MBMS coupled with multivariate analysis for detecting
      the chemical changes associated with brown-rot biodegradation of spruce wood.
AB  - Near infrared (NIR) spectroscopy and pyrolysis-molecular beam mass spectrometry
      (py-MBMS) analysis can be used in conjunction with multivariate regression and
      principal components analysis to differentiate brown-rot-degraded wood from non
      degraded spruce and to follow the temporal changes in wood undergoing brown-rot
      degradation. Regression of NIR test results vs. percent weight loss for Postia
      placenta- and Gloeophyllum trabeum-infected spruce wood blocks yielded a
      correlation coefficient of 0.96. Regression of MBMS test results for the same
      samples yielded a correlation coefficient of 0.96. Principle components analysis
      was used to differentiate non-infected wood and P. placenta- and G. trabeum
      infected wood. These techniques may be used to detect different types of
      biodegradation and to develop a better understanding of the chemical changes that
      the wood undergoes when it is subjected to brown-rot biodegradation.

PMID- 12007663
TI  - Identification of a novel locus that regulates expression of toxin genes in
      Clostridium perfringens.
AB  - A novel gene that regulates the alpha-toxin (plc), kappa-toxin (colA), and theta;
      toxin (pfoA) genes was identified using toxin-negative mutant strains of
      Clostridium perfringens. The cloned 3.2-kb fragment contained the virX gene
      encoding a 51-amino acid polypeptide of unknown function that seemed to be
      responsible for the activation of toxin genes. The virX knock out mutant of wild
      type strain 13 showed a reduced expression of the plc, colA, and pfoA genes,
      which was complemented by the transformation of the intact virX gene. Deletion
      and site-directed mutagenesis studies suggested that the virX gene acts as a
      regulatory RNA rather than as a peptide regulator. The virX locus found in this
      study might play a part in the signal transduction to regulate toxin production
      in C. perfringens.

PMID- 12007664
TI  - Laccase activity in melanin-producing strains of Sinorhizobium meliloti.
AB  - Laccase-like activity was detected in melanin-producing strains of Sinorhizobium
      meliloti mainly in cells at the stationary growth phase when copper was added to
      the medium. The laccase showed both syringaldazine and ABTS (2,2'-azino-bis
      ethylbenzthiazoline-6-sulfonic acid) oxidase activities and was activated by the
      addition of 1.7 mM sodium dodecyl sulfate. Activity was totally inhibited by the
      addition of 1.0 mM EDTA, suggesting that the enzyme is a metal-dependent one. The
      enzyme was found to be cytosolic having an optimum pH of 5.0, an estimated
      molecular mass of 95 kDa and a K(m) of 4 microM for syringaldazine. Both laccase
      and tyrosinase activities were detected in melanin-producing S. meliloti strains.
      Plant growth-promoting (PGP) effect in rice by a laccase-producing S. meliloti
      strain when co-inoculated with Azospirillum brasilense Cd was observed. PGP
      effect by co-inoculation significantly increased plant yield compared to A.
      brasilense by itself. To the best of our knowledge this is the first report on
      laccase production in rhizobia and cooperation between Azospirillum and
      Sinorhizobium in rice.

PMID- 12007665
TI  - Dipeptidyl peptidase with strict substrate specificity of an anaerobic
      periodontopathogen Porphyromonas gingivalis.
AB  - A dipeptidyl peptidase which hydrolyzed Xaa-Ala-p-nitroanilide was purified to
      homogeneity by sequential procedures including ammonium sulfate precipitation,
      ion-exchange chromatography, hydrophobic interaction chromatography, gel
      filtration and isoelectric focusing from the cell extract of Porphyromonas
      gingivalis. The purified enzyme hydrolyzed p-nitroanilide derivatives of Lys-Ala,
      Ala-Ala, and Val-Ala, but not Xaa-Pro. Enzyme activity was maximum at neutral
      pHs. Its molecular mass was 64 kDa with an isoelectric point of 5.7. The enzyme
      belonged to the family of serine peptidases.

PMID- 12007666
TI  - Transcriptional analysis of the recA gene in Streptomyces rimosus: identification
      of the new type of promoter.
AB  - Using primer-extension analysis we identified two transcription start sites for
      the recA gene in Streptomyces rimosus. A longer, weak transcript is initiated
      from the distal SEP promoter that contains a Cheo box like sequence: GAAC-N4
      ATTC. However, the major start site of transcription is a G at position -36 and
      this shorter transcript significantly increases in response to DNA damage by UV
      light. The -35 box (TTGTCA) and -10 box (TAGCGT) of the strong recA promoter are
      only 11 bp apart and this proximal promoter is almost identical to the strong,
      DNA damage-inducible promoter of Mycobacterium tuberculosis recA gene. We
      inspected the Streptomyces coelicolor database and found this type of promoter in
      the upstream regions of many (potentially) UV-inducible genes as well as some
      other genes/ORFs. Moreover, the DNA sequence between the predicted -35 and -10
      boxes is also partially conserved. The consensus sequence for this new type of
      promoter in Streptomyces is: TTGTCAGTGGC-N6-TAGggT.

PMID- 12007668
TI  - Sertraline treatment of obsessive-compulsive disorder: efficacy and tolerability
      of a rapid titration regimen.
AB  - The objective of this study was to compare in a single blind manner, over a
      period of 12 weeks, the efficacy and tolerability of two different titration
      regimens of sertraline in the treatment of OCD: 150 mg/day reached at day five
      from the beginning of therapy (rapid titration regimen) versus 150 mg/day reached
      at day 15 from the beginning (slow titration regimen). Patients with a DSM-IV
      diagnosis of OCD and a Y-BOCS greater or equal to 16 were randomly assigned to
      receive one of the two dosing regimens; an upper target dose of 150 mg/day was
      selected on the basis of a review of mean dosages used in flexible-dose
      sertraline studies. The primary efficacy measure was the Y-BOCS, which was
      completed at baseline and every 2 weeks. Thirty-two patients referred to the
      Anxiety and Mood Disorders Unit of the University of Turin were included in the
      study. Seventeen were assigned to the rapidly escalating dose regimen and 15 to
      the other titration regimen. Twenty-seven (84.4%) patients completed the 12 weeks
      of the study: 14 (82.4%) patients in the rapid and 13 (86.7%) in the slow
      titration regimen. The ANOVA analysis showed a significant difference between
      treatment groups at week 4 and 6 in favor of the rapid titration regimen group;
      this difference faded afterwards. Both titration regimens were effective in
      reducing OC symptoms and were well tolerated: no differences in drop-out or in
      adverse event rates emerged between the two groups. Limitations of the present
      study are the single-blind design and the lack of power to detect differences in
      tolerability.

PMID- 12007669
TI  - Behavioral and neurochemical effects of dopaminergic drugs in models of brain
      injury.
AB  - The dopaminergic drugs, ropinirole and dihydroergocryptine (DHECP) were injected
      subcutaneously (s.c.) at doses of 0.5 and 1 mg/kg/day for 7 days into male rats
      of the Sprague-Dawley strain. The drug pretreatment reverted amnesia induced in
      rats by hypobaric hypopxia and tested in active and passive avoidance tasks.
      Furthermore, a partial restoration of memory retention was found in animals with
      a 2-month brain occlusive ischemia induced by manipulation of the four major
      arteries of the brain. No major changes were found in spontaneous motor activity,
      but drug treatment increased ambulation of animals subjected to acute or chronic
      experimental manipulation. In a model of kainate-induced epilepsy, ropinirole or
      DHECP did not affect seizure parameters, but reduced mortality rate. At the end
      of behavioral procedures, in all animals subjected to hypobaric hypoxia or to
      brain occlusive ischemia glutathione redox index (glutathione reduced/glutathione
      oxidized ratio) was measured in the frontal cortex, striatum and hippocampus. It
      was found that experimental models of brain injury were followed by a decrease of
      reduced glutathione content in all brain areas. The glutathione redox index was
      augmented by ropinirole or DHECP treatment in all brain areas. These behavioral
      and neurochemical findings suggest that ropinirole and DHECP may exert either
      protective activity (as found in animals pretreated with these drugs and exposed
      to hypobaric hypoxia) or reversal of brain injury (as found in animals treated
      after two-month occlusive brain ischemia). Thus, both drugs may be studied as
      therapeutic agents in brain injuries of various origin.

PMID- 12007670
TI  - ApoE genotype influences the biological effect of donepezil on APP metabolism in
      Alzheimer disease: evidence from a peripheral model.
AB  - Three major amyloid precursor protein (APP) forms with apparent molecular weight
      ranging from 106 to 130 kDa are present in human platelets. Alzheimer disease
      (AD) is associated with a decreased APP forms ratio (APPr) between the three
      major forms. A total of 25 mild to moderate AD patients were investigated.
      Platelet APPr was studied before and after 30 days of acetylcholinesterase
      inhibitor treatment (donepezil, 5 mg daily). Patients were grouped into non
      epsilon4 carriers and epsilon4 carriers according to apolipoprotein E (ApoE)
      genotype. At baseline, all patients showed low APPr levels and no significant
      difference was found between the two ApoE subgroups. After treatment, although a
      marked improvement in APPr was observed in most patients, non-epsilon4 carriers
      displayed a higher increase compared to epsilon4 carriers (P<0.0001). The present
      study provides evidence that donepezil influences APP metabolism in platelets,
      and suggests that ApoE genotype might be an important modulating factor for drug
      responsiveness in AD.

PMID- 12007671
TI  - Organotypic rat cerebellar slice culture as a model to analyze the molecular
      pharmacology of GABAA receptors.
AB  - The preservation of the neuronal circuitry in rat cerebellar slice cultures
      provides an advantage in monitoring the development and characterizing the
      pharmacology of GABA(A) receptor subtypes. Sprague-Dawley rats, 8-11 days of age,
      were decapitated, their cerebella were cut into 400-microm slices and transferred
      into culture dishes. Cell viability and organotypic cerebellar organization of
      the culture remained well preserved up to 3 weeks. Autoradiographic procedures
      were introduced in these advanced culture technique and employed [(3)H]Ro 15-4513
      in the absence and presence of 10 microM diazepam to visualize all benzodiazepine
      (BZD) and diazepam-insensitive (DIS) binding sites, respectively. Since
      expression of the alpha6 subunit variant of the GABA(A)/BZD receptor is
      restricted to the cerebellar granule cells and the BZD receptor agonist diazepam
      has very low affinity for this subunit, changes in DIS [(3)H]Ro 15-4513 binding
      sites during cultivation time can be attributed to changes in alpha6 subunit
      expression. A time-dependent development of total and DIS [(3)H]Ro 15-4513
      binding sites were observed in the culture with a trend towards an increase in
      GABA(A) receptor alpha6 subunit levels during the first week. These findings
      suggest that explant preparations can be used to examine morphological changes in
      rat cerebellar slices. In addition, these preparations can be utilized to study
      the pharmacological effects of GABA(A)/BZD selective drugs on postnatal
      development of GABA(A) receptors in rat cerebellum.

PMID- 12007672
TI  - St John's wort (Hypericum perforatum) modulates evoked potentials in guinea pig
      hippocampal slices via AMPA and GABA receptors.
AB  - The effects of an ethanolic extract of the plant Hypericum perforatum L. (St
      John's wort) (HYP) and its hydrosoluble fraction (HYPWS) on electrically evoked
      population spikes and fEPSP were investigated in this study. Concentration
      dependent (10(-6) to 10(-4) g/l) excitatory effects were found. Above
      concentrations of 10(-3) g/l, HYP reduced the evoked responses, whereas HYPWS
      further increased them. Paired pulse facilitation was unaffected with HYPWS (10(
      4) to 10(-2) g/l). The excitatory effects of HYPWS were amplified by the GABA(A)
      and GABA(B) receptor antagonists bicuculline and phaclofen, respectively. These
      excitations were antagonised by the AMPA receptor antagonist CNQX. Excitations
      caused by hypericum were not antagonised by the NMDA receptor antagonists D-APV
      and MK801, the metabotropic glutamate receptor (type I and II) antagonist MCPG,
      or the L-type calcium channel blocker verapamil. Hypericin and hyperforin, two
      components of H. perforatum, were found not to be responsible for the excitatory
      effects of the extract.

PMID- 12007673
TI  - Marinobufagenin (MBG) suppression of ethanol-seeking behavior is associated with
      inhibition of brain cortex Na/K-ATPase in mice.
AB  - In the present study the hypothesis was tested that sodium pump ligands (SPL) can
      modulate alcohol-seeking behavior and that this effect is related to changes in
      Na/K-ATPase activity in the central nervous system. Mice were tested for
      initiation of ethanol intravenous self-administration (IVSA) following i.p.
      pretreatment with vehicle or the endogenous SPL, marinobufagenin (MBG). Drug- and
      experimentally-naive mice acquired IVSA of 2% ethanol during a single 30-min
      session. MBG was found to dose-dependently attenuate (1.25-2.5 microg/kg)
      initiation of ethanol IVSA producing a decrease in the ratio and in the
      difference between operant responses of response-dependent and yoked animals as
      well as a decrease in percentage of mice demonstrating ethanol-seeking behavior.
      Attenuation of the reinforcing effect of ethanol resulting from MBG was
      associated with brain levels of this steroid capable of concurrently inhibiting
      Na/K-ATPase in the brain cortex. We hypothesize that endogenous digitalis-like
      factors could modulate the reinforcing effect of ethanol.

PMID- 12007674
TI  - Niguldipine impairs the protective activity of carbamazepine and phenobarbital in
      amygdala-kindled seizures in rats.
AB  - There is evidence that some calcium (Ca(2+)) channel inhibitors enhance the
      protective activity of antiepileptic drugs. Since clinical trials have not
      provided consistent data on this issue, the objective of this study was to
      evaluate the interaction of a dihydropyridine, niguldipine, with conventional
      antiepileptics in amygdala-kindled rats. Niguldipine (at 7.5 but not at 5 mg/kg)
      displayed a significant anticonvulsant effect, as regards seizure and
      afterdischarge durations in amygdala-kindled convulsions in rats, a model of
      complex partial seizures. No protective effect was observed when niguldipine (5
      mg/kg) was combined with antiepileptics at subeffective doses, i.e. valproate (75
      mg/kg), diphenylhydantoin (40 mg/kg), or clonazepam (0.003 mg/kg). Unexpectedly,
      the combined treatment of niguldipine (5 mg/kg) with carbamazepine (20 mg/kg) or
      phenobarbital (20 mg/kg) resulted in a proconvulsive action. BAY k-8644 (an L
      type Ca(2+) channel activator) did not modify the protective activity of
      niguldipine (7.5 mg/kg) or the opposite action of this dihydropyridine (5 mg/kg)
      in combinations with carbamazepine or phenobarbital. A pharmacokinetic
      interaction is not probable since niguldipine did not affect the free plasma
      levels of the antiepileptics. These data indicate that the opposite actions of
      niguldipine alone or combined with carbamazepine (or phenobarbital) were not
      associated with Ca(2+) channel blockade. The present results may argue against
      the use of niguldipine as an adjuvant antiepileptic or for cardiovascular reasons
      in patients with complex partial seizures.

PMID- 12007675
TI  - Functional genomics and depression research. Beyond the monoamine hypothesis.
AB  - Although antidepressants have been used clinically for more than 50 years, no
      consensus has been reached concerning their precise molecular mechanism of
      action. Functional genomics is a powerful tool that can be used to identify genes
      affected by antidepressants or by other effective therapeutic manipulations.
      Using this tool we have previously identified more than 300 cDNA fragments as
      antidepressant related genes and from these, original cDNA microarrays were
      developed. Some of these candidate genes may encode common functional molecules
      induced by chronic antidepressant treatment. Defining the roles of these genes in
      drug-induced neural plasticity is likely to transform the course of research on
      the biological basis of depression. Such detailed knowledge will have profound
      effects on the diagnosis, prevention, and treatment of depression. Novel
      biological approaches beyond the "monoamine hypothesis" are expected to evoke
      paradigm shifts in the future of depression research.

PMID- 12007676
TI  - The effect of fluvoxamine and sertraline on the opioid withdrawal syndrome: a
      combined in vivo cerebral microdialysis and behavioural study.
AB  - A microdialysis study was undertaken to determine the effect of acute and sub
      chronic administration of the selective serotonin reuptake inhibitor,
      fluvoxamine, and the acute effect of the selective serotonin reuptake inhibitor
      sertraline, on the naloxone precipitated opioid withdrawal induced increase in
      hippocampal noradrenaline levels. This study also determined the effect of
      fluvoxamine and sertraline on opioid withdrawal-induced physical behaviours.
      Naloxone (1 mg kg(-1); i.p.) increased noradrenaline levels in the hippocampus of
      morphine dependent rats 20 min after administration, with peak levels of 267+/
      13% of baseline, occurring 40 min after administration of naloxone. Opioid
      withdrawal-induced physical behaviours were evident in morphine dependent rats 5
      min after a naloxone injection (1 mg kg(-1); i.p.). Acute fluvoxamine or
      sertraline (10 mg kg(-1); i.p.) given 40 min before naloxone (1 mg kg(-1); i.p.)
      did not modify the increased hippocampal noradrenaline levels (242+/-15 and 242+/
      19%, respectively), observed in morphine dependent rats following an naloxone
      injection. Acute fluvoxamine and sertraline (10 mg kg(-1); i.p.) reduced the
      severity of the naloxone precipitated opioid withdrawal syndrome. Sub-chronic
      treatment with fluvoxamine (10 mg kg(-1); i.p.) prevented the naloxone
      precipitated increase in hippocampal noradrenaline levels in morphine dependent
      rats. Furthermore, sub-chronic fluvoxamine produced a significantly reduced
      baseline level of noradrenaline in these rats which was 52.5+/-8% of baseline 40
      min after naloxone.

PMID- 12007677
TI  - Carbamazepine augmentation in depressive patients non-responding to citalopram: a
      pharmacokinetic and clinical pilot study.
AB  - Citalopram is a chiral antidepressant drug. Its eutomer, S-citalopram
      (escitalopram), has recently been introduced as an antidepressant. In an open
      pilot study, four outpatients and two inpatients with a major depressive episode
      (ICD-10), and who were nonresponders to a 4-week pretreatment with 40-60 mg/day
      citalopram, were comedicated for another 4-week period with carbamazepine (200
      400 mg/day). Some of the patients suffered also from comorbidities: Phobic
      anxiety disorder with panic attacks (n=2), generalised anxiety disorder, alcohol
      abuse, dependent personality disorder, hypertension (n=1). After a 4-week
      augmentation therapy with carbamazepine, a significant (P<0.03) decrease of the
      plasma concentrations of S-citalopram and R-citalopram, by 27 and 31%,
      respectively, was observed. Apparently, the probable induction of CYP3A4 by
      carbamazepine results in a nonstereoselective increase in N-demethylation of
      citalopram. Moreover, there was a significant (P<0.03) decrease of the ratio S/R
      citalopram propionic acid derivative, the formation of it being partly regulated
      by MAO-A and MAO-B. Already, within 1 week after addition of carbamazepine, there
      was a slight but significant (P<0.03) decrease of the MADRS depression scores,
      from 27.0+/-7.7 (mean+/-S.D.) to 23.3+/-6.6, and the final score on day 56 was
      18.8+/-10.9. The treatment was generally well tolerated. There was no evidence of
      occurrence of a serotonin syndrome. After augmentation with carbamazepine,
      treatment related adverse events were: Nausea in one case, diarrhea in one case,
      and rash in two cases. In conclusion, the results of this pilot study suggest
      that carbamazepine augmentation of a citalopram treatment in previous
      nonresponders to citalopram may be clinically useful, but that in addition
      carbamazepine can lead to a decrease of the plasma concentrations of the active
      enantiomer escitalopram.

PMID- 12007678
TI  - Chronic clozapine, but not haloperidol, treatment affects rat brain vesicular
      monoamine transporter 2.
AB  - We compared the effect of chronic clozapine and haloperidol treatment on the
      expression of rat brain vesicular monoamine transporter (VMAT(2)) as well as on
      the membranal presynaptic transporters for serotonin, dopamine and noradrenaline.
      Rats were treated for 21 days with clozapine (25 mg/kg), haloperidol (0.5 mg/kg)
      or saline. VMAT(2) expression was assessed on the protein level by high affinity
      [3H]dihydrotetrabenazine binding using autoradiography, and on the mRNA level by
      in situ hybridization. The densities of the monoamine transporters were evaluated
      by autoradiography using specific ligands. Clozapine administration led to an
      increase in [3H]TBZOH binding in the nucleus accumbens, prefrontal cortex and
      striatum, whereas haloperidol had no effect on VMAT(2) binding capacity. The
      clozapine-induced increase in VMAT(2) was accompanied by a parallel increase in
      the membrane serotonin transporter in the prefrontal cortex and the striatum.
      Haloperidol induced an increase in the serotonin transporter in the striatum and
      the core of the nucleus accumbens. The special effect of clozapine on VMAT(2)
      expression may be relevant to its unique therapeutic advantages.

PMID- 12007679
TI  - Elevated serum S100B protein in drug-free bipolar patients during first manic
      episode: a pilot study.
AB  - S100B protein is a calcium-binding protein mostly derived from glial cells, which
      exerts trophic or toxic effects on neural cells depending on its concentration.
      Since serum S100B levels has been tested as a potential marker in
      neuropsychiatric disorders, and structural abnormalities on glial cells have been
      recently associated with bipolar disorder patients, we conducted this preliminary
      study to examine if S100B serum levels are altered during first manic episode. We
      quantitated S100B in serum of 40 subjects (20 unmedicated patients during manic
      episode and 20 healthy matched controls). The mean+/-S.D. values for S100B for
      bipolar subjects were 0.065+/-0.068 microg/l and 0.018+/-0.029 microg/l for
      healthy controls. Increased levels of S100B in bipolar mania was statistically
      significant (Wilcoxon signed ranks test, Z=-2.45, P=0.01). These preliminary
      findings suggest that mania may increase the levels of S100B in serum of bipolar
      disorder patients, which could be related to adaptative neural mechanisms in
      bipolar mania.

PMID- 12007680
TI  - PRESTO (a mammoth trial that could have been prevented), HPS and REMATCH.

PMID- 12007681
TI  - Percutaneous intervention for atherosclerotic disease in saphenous vein grafts.
AB  - The long term benefit of coronary artery bypass surgery (CABG) is limited by
      development of atherosclerotic disease in the bypass conduits. Percutaneous
      revascularisation is frequently the preferred method of treated symptomatic
      saphenous vein graft (SVG) atherosclerotic disease. The immediate and long term
      results of percutaneous intervention for SVGs is reviewed. Therapeutic
      considerations as well as novel technical advances are overviewed

PMID- 12007682
TI  - Value of intracardiac ultrasound in the diagnosis of arrhythmogenic right
      ventricular dysplasia-cardiomyopathy.
AB  - The value of imaging techniques such as transthoracic echocardiography,
      angiography and magnetic resonance imaging in the diagnosis of arrhythmogenic
      right ventricular dysplasia-cardiomyopathy (ARVD) is limited. First experiences
      with intracardiac ultrasound have been made during electrophysiological
      interventions. The ability of using intracardiac ultrasound in ARVD should be
      tested. In 25 patients with IFSC/ESC criteria of ARVD (nine males, 16 females)
      with a mean age of 54 (29-78) years suffering from sustained ventricular
      tachycardia in three cases, positive family history in four cases and syncopes in
      six cases intracardiac ultrasound was done using 6 French (Fr) 12.5 MHz catheters
      and the CLEAR VIEW ULTRA Intravascular System (Boston Scientific). Images were
      taken from the right ventricular apex, outflow tract and infundibulum. Results
      were compared to selective right ventricular angiography. Right ventricular (RV)
      angiography revealed bulges and a partial or complete loss of trabecular
      structure in 22 cases at the apex, in 13 cases at the infundibulum and in 14
      cases at the right ventricular outflow tract. Intracardiac echocardiography was
      able to demonstrate sacculations in all patients at the apex, in 20 cases at the
      infundibulum and in 16 patients at the right ventricular outflow tract.
      Sacculations in all segments of the right ventricle were based on a partial or
      complete loss of trabecular structure. A whole of 36 segments presented with wall
      thinning (<3 mm) and 15 segments with normal wall structure and wall thickening
      of surrounding myocardium (>4 mm). In 26 segments the structure of right
      ventricular wall was inhomogeneous. In comparison to angiography as the 'gold
      standard' intracardiac ultrasound presented with additional details in 12 cases
      and the demonstration of angiographic misinterpretation in one case. Intracardiac
      ultrasound in ARVD is feasible in all cases with 6 Fr 12.5 MHz catheters and
      provides additional information to the angiographic phenomenon of bulges and to
      the aspect of tissue characterisation.

PMID- 12007683
TI  - Induced ischemia detected by dobutamine stress echocardiography in coronary heart
      disease patients after myocardial re-vascularization. Experience in a District
      General Hospital.
AB  - Most episodes of myocardial ischemia in patients with known coronary artery
      disease (CHD) are asymptomatic. Silent myocardial ischemia (SMI) is an important
      predictor of adverse outcome in patients with proven coronary artery disease.
      beta-blockers are effective in suppressing ischemia, and improve clinical outcome
      in patients with coronary artery disease. At present, it is common practice to
      stop treatment with beta-blockers in clinically asymptomatic patients after
      coronary artery bypass graft (CABG) and/or myocardial re-vascularization
      (PTCA/Stent), although the possible presence of SMI/inducible ischemia after
      myocardial re-vascularization is not known. We examined 56 asymptomatic CHD
      patients after coronary artery bypass graft (n=36), percutaneous coronary
      angioplasty PTCA/stent (n=15), or both (n=5); therapy with beta-blockers was
      stopped in all of them after myocardial revascularization. All these patients
      underwent a dobutamine stress echocardiography test (DSE test). The DSE test was
      proposed to these asymptomatic CHD patients to investigate the possible presence
      of SMI/inducible ischemia after myocardial re-vascularization. All patients had
      history of myocardial infarction or evidence of mildly impaired left ventricular
      function at rest as assessed by cardiac catheterization. Abnormal DSE studies
      occurred in eight of the 56 patients (14%; 95% C.I.: 6-26%). Therapeutic
      approaches specifically targeted at reducing total ischaemic burden include
      pharmacologic therapy and myocardial revascularization. On the basis of these
      data, it can be concluded that asymptomatic CHD patients after myocardial re
      vascularization must be re-evaluated to rule out SMI/inducible ischemia that can
      be treated (e.g. with beta-blockers) reducing cardiovascular morbidity and
      mortality.

PMID- 12007684
TI  - Reactive oxygen species contribute to contractile dysfunction following rapid
      ventricular pacing in dogs.
AB  - BACKGROUND: Ventricular tachyarrhythmias may produce subsequent myocardial
      dysfunction through the formation of oxygen-derived free radicals. We tested the
      hypothesis that the antioxidant N-acetylcysteine enhances recovery of contractile
      function after rapid ventricular pacing. METHODS: Barbiturate-anesthetized dogs
      were instrumented for measurement of systemic and coronary hemodynamics and
      subendocardial segment shortening (%SS). All dogs were subjected to 3 h of rapid
      ventricular pacing (230 beats/min) followed by a 2 h recovery period. In three
      groups (n=8 each), dogs received intravenous 0.9% saline or N-acetylcysteine (50
      or 150 mg/kg over 60 min) in a random manner before pacing. RESULTS: N
      acetylcysteine did not affect systemic and coronary hemodynamics or alter
      regional myocardial contractility. Rapid ventricular pacing significantly
      (P<0.05) increased rate-pressure product and left ventricular end-diastolic
      pressure and decreased +dP/dt(max). Rapid ventricular pacing produced equivalent
      degrees of contractile dysfunction in dogs receiving saline or N-acetylcysteine
      (e.g. %SS of 14.7+/-1.8 to -3.8+/-2.7% before and during pacing in saline
      pretreated dogs). Dogs receiving the 150 mg/kg dose of N-acetylcysteine
      demonstrated greater recovery of contractile function than those pretreated with
      saline or the 50 mg/kg dose (e.g. %SS of 12.3+/-1.7% compared to 7.0+/-2.0% 2 h
      after pacing in dogs receiving saline). No differences in systemic and coronary
      hemodynamics were observed between groups during recovery from pacing.
      CONCLUSIONS: The results indicate that the N-acetylcysteine enhances recovery of
      contractile function after rapid ventricular pacing independent of alterations in
      systemic and coronary hemodynamics and imply that reactive oxygen species are an
      important component of the contractile dysfunction following rapid pacing in
      vivo.

PMID- 12007685
TI  - Myocardial ischemia and autonomic activity in dippers and non-dippers with
      coronary artery disease: assessment of normotensive and hypertensive patients.
AB  - OBJECTIVES: The aim of this study was to assess the relations between the
      circadian variations of blood pressure (BP) and the pattern of ischemia and
      autonomic activity in normotensive and hypertensive patients with coronary artery
      disease (CAD). PATIENTS AND METHODS: On the basis of the results of ambulatory BP
      monitoring, 115 patients with stable CAD were divided into Group 1 (with arterial
      hypertension) and Group 2 (normotensives). Groups were subdivided into dippers
      and non-dippers. Holter monitoring was performed to assess the occurrence and
      circadian pattern of ischemic episodes. Time domain and frequency domain HRV
      analyses were performed to evaluate the autonomic activity. RESULTS: The total
      number of ischemic episodes was similar in dippers and non-dippers. Non-dippers
      had a greater number of silent episodes and a different circadian pattern of
      ischemia with more night episodes. Among the time-domain HRV parameters, only
      SDNN was similar in dippers and non-dippers. Non-dippers had lower pNN50 and
      rMSSD-the parameters expressing parasympathetic activity. Differences between
      diurnal and nocturnal results of spectral HRV analysis were observed in dipper
      patients only. They presented an elevation of HF power and a decline of LF power
      at night. All differences between dippers and non-dippers were of similar
      significance in both hypertensives and normotensives. CONCLUSIONS: A lack of a
      nocturnal fall in BP is present in normotensive and hypertensive patients with
      CAD. Non-dippers with CAD had silent and nighttime ischemia more often. They also
      had an abnormal pattern of autonomic activity with higher sympathetic and lower
      parasympathetic modulation.

PMID- 12007686
TI  - Serum levels of selected adhesion molecules in patients with coronary artery
      disease.
AB  - BACKGROUND: Adhesion molecules have been suggested as mediators of
      atherosclerotic inflammatory process. They may contribute to the pathogenesis of
      stable and unstable angina. METHODS: The study group consisted of 59 patients
      with coronary artery disease: 27 patients with stable exertional angina (group
      A), 32 patients with unstable angina (group B). 20 healthy persons acted as
      controls (group C). Serum levels of soluble Intercellular Adhesion Molecule 1
      (sICAM-1), Vascular Cell Adhesion Molecule 1 (sVCAM-1), sE-selectin, sP-selectin
      were measured both before and after the treadmill ECG stress test in groups A and
      C. In group B the measurements were carried out at 6, 24, and 48 hours following
      an episode of chest pain. RESULTS: There were no differences between the baseline
      serum levels of adhesion molecules as determined in groups A and C. In patients
      with stable angina, the post-exercise concentrations of sE-selectin were
      significantly higher (68.8+/-29 ng/ml) in comparison to both baseline- (38.7+/-15
      ng/ml), and group C-values (pre-exercise: 35.1+/-16; post-exercise: 49.9+/-15
      ng/ml). In unstable patients, serum sP-selectin (190.1+/-99 ng/ml) and sVCAM-1
      levels (1359+/-299 ng/ml) were higher when compared to those found in groups A
      (142.3+/-24; 962+/-352 ng/ml, respectively) and C (136.4+/-33; 851+/-168 ng/ml,
      respectively). CONCLUSIONS: Serum levels of soluble adhesion molecules in
      patients with stable angina are comparable to those of healthy persons. Stress
      test-induced increase of sE-selectin concentration may reflect endothelial
      response to exercise. Unstable angina is characterized by significant elevation
      of sP-selectin and sVCAM-1 serum levels which seems to be related to enhanced
      platelets and leukocytes activation.

PMID- 12007687
TI  - B-type natriuretic peptide after percutaneous transluminal septal myocardial
      ablation.
AB  - BACKGROUND: Plasma level of B-type natriuretic peptide is a sensitive marker of
      left ventricular dysfunction and the level is markedly elevated in patients with
      hypertrophic obstructive cardiomyopathy. Percutaneous transluminal septal
      myocardial ablation, a catheter-based treatment of hypertrophic obstructive
      cardiomyopathy, has been widely used as a new therapeutic option for the disease.
      This study was designed to evaluate clinical implications of natriuretic peptides
      after the new treatment. METHODS: Seven consecutive patients with hypertrophic
      obstructive cardiomyopathy unresponsive to usual medical treatments (age: 57.9+/
      22.0 years) were enrolled in the study. Serial changes in atrial and B-type
      natriuretic peptide in plasma were examined after percutaneous transluminal
      septal myocardial ablation. RESULTS: Atrial and B-type natriuretic peptides
      levels (pg/ml, mean+/-S.D.) at baseline were higher in hypertrophic obstructive
      cardiomyopathy than in control (80.0+/-43.0 vs. 12.8+/-5.2, P<0.0001; 858.0+/
      458.4 vs. 12.4+/-7.0, P<0.0001; respectively). Left ventricular outflow-tract
      pressure gradient (mmHg) immediately decreased from 115.3+/-23.3 to 30.6+/-12.4
      (P<0.0001) after the treatment and concomitantly B-type natriuretic peptide level
      decreased (858.0+/-458.4 to 264.1+/-137.7, P=0.0084). The level re-increased and
      peaked at the 2nd day (634.4+/-429.6) and gradually decreased again until 4
      weeks. Reduction rate of left ventricular outflow-tract pressure gradient between
      before and 4 weeks after percutaneous transluminal septal myocardial ablation
      positively correlated with that of B-type natriuretic peptide (r(2)=0.817,
      P=0.0053). Changes in atrial natriuretic peptide were not significant in contrast
      to those of B-type natriuretic peptide. CONCLUSIONS: Plasma B-type natriuretic
      peptide level could be useful to predict the effects of percutaneous transluminal
      septal myocardial ablation in patients with hypertrophic obstructive
      cardiomyopathy.

PMID- 12007688
TI  - Atrial natriuretic peptide level after cardioversion of chronic atrial
      fibrillation.
AB  - Heart endocrine studies concerning patients with chronic atrial fibrillation (AF)
      have become increasingly important. Atrial natriuretic peptide (ANP) is released
      from atrial myocytes. The increased level of ANP in patients with AF is probably
      caused by the hemodynamic effect of the arrhythmia. The aim of this study was to
      explore plasma ANP levels in patients with chronic AF and to describe plasma ANP
      concentration changes following sinus rhythm (SR) restoration. The study group
      was comprised of 42 patients, aged between 43 and 76 years with chronic AF (more
      than 1 month) and a relatively controlled ventricular response (85.8+/-11.3
      beats/min). Plasma ANP levels were measured before and 24 h after AF
      cardioversion. The control group comprised of 11 subjects. All had normal SR
      without history of AF and were compatible in age, sex and concomitant diseases
      with the examined group. ANP level values were expressed as mean+/-standard
      deviation. The mean plasma ANP level in the AF group was significantly higher
      than in the control group (59.5+/-15.6 vs. 34.3+/-10.2 pg/ml, P<0,001).
      Electrical or pharmacological cardioversion was performed in 42 patients. SR was
      successfully restored in 35 patients. Plasma ANP concentrations decreased
      significantly from baseline values (from 59.4+/-16.6 to 31.4+/-15.0 pg/ml,
      P<0.001) 24 h after cardioversion in the successful group, while they remained
      unchanged (60.2+/-10.7 to 59.4+/-10.4 pg/ml, NS) in patients with an unsuccessful
      cardioversion. CONCLUSION: The mean concentration of ANP in patients with chronic
      AF was nearly two-times higher than in the control group with sinus rhythm.
      Conversion to SR was associated with a significant decrease and normalization in
      plasma ANP concentrations.

PMID- 12007689
TI  - Supravalvular aortic stenosis in cutis laxa syndrome: a case report.

PMID- 12007690
TI  - Isolated coronary arterial dysplasia in an infant.

PMID- 12007691
TI  - Hypertrophic cardiomyopathy with massive hypertrophy, amiodarone treatment and
      high defibrillation threshold at cardioverter-defibrillator implant.

PMID- 12007692
TI  - Percutaneous balloon angioplasty of inferior vena cava in Budd-Chiari syndrome
      R1.
AB  - This study was to evaluate the clinical effects of percutaneous balloon
      angioplasty of Budd-Chiari syndrome (BCS) caused by inferior vena cava (IVC)
      obstruction. Between 1993 and 1999, 28 men and 14 women with mean age of 44+/-12
      years underwent percutaneous balloon angioplasty for primary BCS. Color Doppler
      ultrasound and venography showed membranous and segmental obstruction of IVC in
      29 and 13 patients, respectively. Fourteen patients also had left- and/or mid
      hepatic vein obstruction. Angioplasty of IVC was successful in 41 patients
      (97.6%), resulting in a reduction of pressure gradient between IVC and the right
      atrium from 15.0+/-2.5 to 5.5+/-0.8 mmHg (P<0.01). A stent was placed in the site
      of obstruction in the patient with unsuccessful balloon angioplasty. Patients
      with successful angioplasty or stent placement had significant improvement in
      clinical symptoms indicated by a reduction in hepatomegaly and the degree of
      ascites. No specific attempt was made to treat the occluded left- and/or mid
      hepatic vein due to the presence of potent right hepatic vein. Over the follow-up
      period of 32+/-12 months, restenosis of IVC occurred in only one patient (2.4%),
      which was redilated successfully. Percutaneous balloon angioplasty is a safe and
      effective therapy for Budd-Chiari syndrome caused by IVC obstruction, therefore
      should be the first choice of treatment for this condition.

PMID- 12007693
TI  - Alarming atrioventricular block and mitral valve prolapse in the Kearns-Sayre
      syndrome.
AB  - Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized
      by the invariant triad: onset before 20, progressive external ophthalmoplegia and
      pigmentary retinal degeneration, plus at least one of the following: complete (or
      not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl.
      Autopsies from patients with KSS revealed widespread tissue distribution mtDNA
      deletions. These deletions result in significantly lower activities of the
      enzymes of the respiratory chain. The same deletion of mitochondrial DNA present
      in skeletal muscle is found in myocardial tissue. An 18-year-old girl diagnosed
      with the KSS was admitted to our hospital because of an upper respiratory tract
      infection and dysphagia. ECG showed cardiac conduction defects. The patient had
      no history of syncope. At her surface ECG there was a complete RBBB (QRS duration
      approximately 130 ms), a clockwise rotation with an axis of approximately 90
      degrees and a slight QT prolongation (420 ms). Echocardiography showed prolapse
      with thickening and degeneration of both mitral valve leaflets but without mitral
      regurgitation. The patient was started on a diet rich in potassium and
      pharmaceutical therapy with magnesium oxide (240 mg of elemental Mg p.o. per
      day), 1 g of calcium carbonate t.i.d., vitamin D (calcitriol 0.25 microg p.o. per
      day) and coenzyme Q(10) 100 mg daily and discharged 6 days later with slightly
      improved biochemical profile but apparent clinical improvement. Urgent pacemaker
      implantation was decided but unfortunately the patient died due to acute cardiac
      arrest 10 days later.

PMID- 12007694
TI  - Acute myocardial infarction in a young woman with severe ulcerative colitis.
AB  - In this report we present a case of a 28-year-old woman who was admitted to our
      emergency room complaining of chest pain. Her clinical ECG and biochemical
      evaluation was consistent with acute nonatherogenic myocardial infarction.
      Subsequent work is revealed that she was suffering from ulcerative colitis with
      acute exacerbation since last week. We discussed triggering factors for
      thrombogenic and inflammatory tendency of patient with comprehensive review of
      literature to clarify the causal relationship.

PMID- 12007695
TI  - Acute myocardial infarction secondary thrombosis associated with ovarial
      hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is one of the most serious complication
      of controlled ovarian stimulation. Cerebral infarction, myocardial infarction,
      death and vascular thrombotic events associated with OHSS had been reported. We
      report a case of a patient with myocardial infarction associated with OHSS.

PMID- 12007696
TI  - Normal coronary arteries and isolated, regional, left ventricular dysfunction in
      myotonic dystrophy: a case report.
AB  - Development of cardiomyopathy in myotonic dystrophy is rare. Regional ventricular
      abnormality in the presence of normal coronary vessels has not been reported in
      this condition. We describe a case of isolated, regional, left ventricular
      dysfunction with corresponding defects on nuclear perfusion imaging in a patient
      with classical myotonic dystrophy and normal coronary arteries.

PMID- 12007697
TI  - Acute superior vena cava and right atrial tamponade in an infant after open heart
      surgery.
AB  - Early postoperative localized cardiac tamponade occurred in a 4-month old infant
      after ventricular septal defect repair. The clinical findings were as for acute
      superior vena cava syndrome. The diagnosis was accurately made using
      echocardiography and measurement of the superior vena cava and right atrial
      pressure. Surgical revision was necessary to remove a large clot from the
      superior vena cava-right atrium junction.

PMID- 12007698
TI  - Anti-diabetic activity of alcoholic extract of Aerva lanata (L.) Juss. ex
      Schultes in rats.
AB  - Aerva lanata (L.) Juss. ex Schultes commonly known as 'Sunny khur' is widely used
      in Indian folk medicine for the treatment of Diabetes mellitus. This study was
      undertaken to evaluate the effect of an alcoholic extract of A. lanata (AAL) on
      blood glucose and other biochemical parameters in alloxan-induced diabetic rats.
      AAL was found to reduce the increase of blood sugar in alloxan-induced diabetic
      rats (42% at 375 mg/kg and 48% at 500 mg/kg body weight). Chronic administration
      of AAL significantly (P<0.001) reduced the blood sugar of alloxan induced
      diabetic rats for 2 weeks. Also the extract prevented a decrease in body weight
      and reduced the increased lipid peroxides in alloxan induced diabetic rats. These
      results suggest that the AAL posseses anti-diabetic activity and is able to
      ameliorate biochemical damages in alloxan induced diabetic rats.

PMID- 12007699
TI  - Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal
      and streptozotocin diabetic rats.
AB  - The purpose of this study was to examine the hypoglycaemic effect of the
      lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber
      (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and
      repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10
      mg/kg produced a slight and significant decrease in plasma glucose levels in
      normal rats 6 h after administration and after 3 weeks of treatment. AI reduced
      plasma glucose levels of streptozotocin diabetic rats from 337+/-9.3 to 102.2+/
      17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral
      administration of AI to streptozotocin diabetic rats significantly decreased the
      plasma glucose levels after 1 week of treatment (112+/-14.4 mg/dl at 1 week vs
      337+/-9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased
      thereafter and showed a rapid normalisation after 1 week of AI treatment. It is
      concluded that these results demonstrated that the water extract of the whole
      plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support
      therefore, its traditional use in diabetes mellitus control.

PMID- 12007700
TI  - Cupressus lusitanica (Cupressaceae) leaf extract induces apoptosis in cancer
      cells.
AB  - A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate
      cytotoxicity in a panel of cancer cell lines. Cell death was due to apoptosis, as
      assessed by morphologic features (chromatin condensation and apoptotic bodies
      formation) and specific DNA fragmentation detected by in situ end-labeling of DNA
      breaks (TUNEL). The apoptotic cell death was induced timely in a dose-dependent
      manner. Despite the absence of changes in the expression levels of antiapoptotic
      protein Bcl-2, proapoptotic Bax protein variants omega and delta were increased.
      These results warrant further research of possible antitumor compounds in this
      plant.

PMID- 12007701
TI  - Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal
      cancer cells.
AB  - Sangre de grado is an ethnomedicinal red tree sap obtained from Croton spp. that
      is used to treat gastrointestinal ulcers, cancer and to promote wound healing. To
      evaluate the potential role of sangre de grado (SdG) in cancer we examined its
      effects on human cancer cells, AGS (stomach), HT29 and T84 (colon). Viability of
      cells treated with SdG (10-200 microg/ml) decreased (P<0.01) in a dose dependent
      manner measured over a 24-h period. Cell proliferation at 48 h decreased (P<0.01)
      in all cells treated with SdG (>100 microg/ml). When cells in suspension were
      treated with SdG (100 microg/ml) cell adherence was severely compromised (>85%).
      Cells treated with SdG (100 microg/ml) underwent apoptosis as detected by nucleus
      condensation and DNA fragmentation determined by ELISA, and flow cytometry.
      Morphological changes as assessed by acridine orange. These effects were similar
      to that observed with Taxol (30 microM). A significant alteration of microtubular
      architecture was equally observed in both stomach and colon cancer cells exposed
      to SdG (100 microg/ml). The induction of apoptosis and microtubule damage in AGS,
      HT29 and T84 cells suggest that sangre de grado should be evaluated further as a
      potential source of anti-cancer agents.

PMID- 12007702
TI  - Interaction of lectin-like proteins of South African medicinal plants with
      Staphylococcus aureus and Bacillus subtilis.
AB  - Lectin-like proteins from seven medicinal plant species of South Africa
      possessing well-documented antibacterial effects were examined for the
      interaction with two Gram-positive bacterial pathogens Staphylococcus aureus and
      Bacillus subtilis. Agglutinins elicited selective aggregation reactions with
      bacterial strains. Hypoxis hemerocallidea and Combretum mkhuzense agglutinins
      aggregated S. aureus at 4 and 5 microg ml(-1) of protein concentrations,
      respectively. B. subtilis was aggregated by C. mkhuzense, Kniphofia spp. and
      Tulbaghia violacea agglutinins at relatively high concentrations. The inhibition
      of bacterial growth at the initial stages of multiplication was observed in the
      presence of particular plant agglutinins. Suggestions are given about possible
      employment of agglutinins from medicinal plants in clinical microbiology. The
      possible contribution of lectin-like proteins to pharmacological effects
      associated with microbial infections is presumed.

PMID- 12007703
TI  - A study of the composition of some eye cosmetics (kohls) used in the United Arab
      Emirates.
AB  - A total of 23 kohl samples was analyzed using X-ray powder diffraction (XRPD) and
      scanning electron microscopy (SEM). Nineteen samples were obtained in Abu Dhabi
      and four in Dubai. None of the samples were made in the United Arab Emirates. The
      main component of 11 samples was found to be galena (PbS). For the remaining 12
      samples, the main component was found to be one of the following: amorphous
      carbon, zincite (ZnO), sassolite (H(3)BO(3)) or calcite/aragonite (CaCO(3)).

PMID- 12007704
TI  - Evaluation of chemical constituents and free-radical scavenging activity of
      Swarnabhasma (gold ash), an ayurvedic drug.
AB  - From ancient times, Swarnabhasma (gold ash) has been used in several clinical
      manifestations including loss of memory, defective eyesight, infertility, overall
      body weakness and incidence of early aging. Swarnabhasma has been used by
      Ayurvedic physicians to treat different diseases like bronchial asthma,
      rheumatoid arthritis, diabetes mellitus, nervous disorders, etc. In the present
      investigation, Swarnabhasma was prepared after proper purification and
      calcination as per Ayurvedic pharmacy which consisted of Realger (As(2)S(2)),
      Lead oxide (Pb(3)O(4)), Pure gold (Au) and Latex of Calotropis gigantea.
      Qualitative analyses indicated that Swarnabhasma contained not only gold but also
      several microelements (Fe, Al, Cu, Zn, Co, Mg, Ca, As, Pb, etc.). Infrared
      spectroscopy showed that the material was free from any organic compound. The
      metal content in the bhasma was determined by atomic absorption spectrometry.
      Acute oral administration of Swarnabhasma showed no mortality in mice (up to 1 ml
      /20 g b.w. of Swarnabhasma suspension containing 1mg of drug). Chronic
      administration of Swarnabhasma also showed no toxicity as judged by SGPT, SGOT,
      serum creatinine and serum urea level and histological studies. In an
      experimental animal model, chronic Swarnabhasma-treated animals showed
      significantly increased superoxide dismutase and catalase activity, two enzymes
      that reduce free radical concentrations in the body.

PMID- 12007705
TI  - Ethanol extract of propolis inhibits nitric oxide synthase gene expression and
      enzyme activity.
AB  - Propolis obtained from honeybee hives has been used in Oriental folk medicine as
      an anti-inflammatory, anti-carcinogenic, or immunomodulatory agent. However, the
      molecular basis for anti-inflammatory properties of propolis has not yet been
      established. Since nitric oxide (NO) synthesized by inducible nitric oxide
      synthase (iNOS) has been known to be involved in inflammatory and autoimmune
      mediated tissue destruction, modulation of NO synthesis or action represents a
      new approach to the treatment of inflammatory and autoimmune diseases. The
      present study, therefore, examined effects of ethanol extract of propolis (EEP)
      on iNOS expression and activity of iNOS enzyme itself. Treatment of RAW 264.7
      cells with EEP significantly inhibited NO production and iNOS protein expression
      induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). EEP also
      inhibited iNOS mRNA expression and nuclear factor-kappa B (NF-kappaB) binding
      activity in a concentration-dependent manner. Furthermore, transfection of RAW
      264.7 cells with iNOS promoter linked to a chloramphenicol acetyltransferase
      (CAT) reporter gene, revealed that EEP inhibited the iNOS promoter activity
      induced by LPS plus IFN-gamma through the NF-kappaB sites of the iNOS promoter.
      In addition, EEP directly interfered with the catalytic activity of murine
      recombinant iNOS enzyme. These results suggest that EEP may exert its anti
      inflammatory effect by inhibiting the iNOS gene expression via action on the NF
      kappaB sites in the iNOS promoter and by directly inhibiting the catalytic
      activity of iNOS.

PMID- 12007706
TI  - In vitro antiplasmodial activity of extracts of Argentinian plants.
AB  - Fifteen extracts from nine selected Argentine medicinal plants were tested for
      their antiplasmodial activity in vitro by assessing their ability to inhibit the
      uptake of [3H]-hypoxanthine into the Plasmodium falciparum K1
      pyrimethamine/chloroquine resistant strain. The methanol extract of Satureja
      parvifolia showed good antiplasmodial activity (IC(50) 3 microg/ml). Inhibition
      of the growth of P. falciparum was also observed with aqueous extracts of
      Buddleja globosa and S. parvifolia.

PMID- 12007707
TI  - Reconstructed materia medica of the Medieval and Ottoman al-Sham.
AB  - This article presents the results of a study of the medicinal uses of natural
      substances in medieval and Ottoman al-Sham (the Levant). It involved a meticulous
      survey of a wide range of historical sources spanning approximately 1100 years
      and including medical and pharmacological literature, travelogues, geographical
      and agricultural literature, dictionaries, archives, the Genizah and other
      medieval sources. Our main goal was to arrive at a reconstruction of the
      unwritten materia medica of the medieval and Ottoman Levant. Of the many and
      varied medicinal substances on which we were able to extract information, we were
      able to identify 286. These are presented according to the following
      classification: 234 species of plants (81.8%); 27 species of animals (9.5%); 15
      kinds of minerals (5.2%) and 10 substances of other or mixed origin (3.5%).
      Analysis of the data showed that the region under study served as the geographic
      origin of the majority of the substances, only a minority of the materials was
      imported. The main reason for this is the geographic location of the Levant as a
      junction between three continents, as a cultural meeting point and as trade
      center. Finally, our data revealed that the al-Sham region was an independent
      source of production and marketing of medicinal substances during the medieval
      and Ottoman periods.

PMID- 12007708
TI  - Anti-inflammatory, analgesic activity and acute toxicity of Glaucium grandiflorum
      extract.
AB  - The species of Glaucium have been used in Iranian herbal medicine as laxative,
      hypnotic, antidiabetic agents and also in the treatment of dermatitis. The anti
      inflammatory and analgesic effects of the aerial parts of Glaucium grandiflorum
      Boiss & Huet (Papaveraceae), a native plant of Iran, were studied using
      carrageenan induced edema, formalin and hot plate tests. The G. grandiflorum
      extract at the dose of 200 mg/kg had more edema inhibition than indomethacin at
      the doses of 10 (P<0.01) and 8 mg/kg (P<0.001) in the carrageenan test. The
      ED(50) (i.p.) in the edema induced by carrageenan was 13.59 mg/kg. In formalin
      test, the extract (60-90 mg/kg, i.p.) caused graded inhibition of both phases of
      formalin-induced pain. In hot plate test, the i.p. administration of the extract
      at the doses of 60, 70, 80 and 90 mg/kg significantly raised the pain threshold
      at a observation time of 45 min in comparison with control (P<0.001). The
      extract, at the antinociceptive doses, did not affect motor coordination of
      animals when assessed in the rotarod model. The 72 h acute LD(50) value of this
      extract after i.p. administration in mice was 797.94 mg/kg.

PMID- 12007709
TI  - Anthelmintic activity of preparations derived from Myrsine africana and Rapanea
      melanophloeos against the nematode parasite, Haemonchus contortus, of sheep.
AB  - Myrsine africana L. and Rapanea melanophloeos L. belong to the plant family
      Myrsinaceae. Various rural communities in Kenya, such as smallholder farmers and
      pastoralists, use them to treat their livestock. The anthelmintic
      effects/activities of leaves and fruits of M. africana and fruits of R.
      melanophloeos were tested in sheep experimentally infected with the nematode
      parasite Haemonchus contortus. Male lambs were infected with 3000-5000 third
      stage larvae of H. contortus and treated 28 days after inoculation with
      concoctions made from leaves or fruits of the plants. No significant reduction in
      faecal nematode egg counts was observed with any of the concoctions at any of the
      doses tested. Packed red cell volume decreased and live weight increased at
      similar rates in treated and control groups, thus there was no significant effect
      of treatment. The results showed that the tested extracts of the M. africana and
      R. melanophloeos were not efficacious against H. contortus in sheep.

PMID- 12007710
TI  - Studies on antimycotic properties of Datura metel.
AB  - The hexane, chloroform, acetone and methanolic fractions of Datura metel L. were
      investigated for antifungal properties using pathogenic species of Aspergillus.
      The chloroform fraction was found to be endowed with antifungal activity. The
      minimum inhibitory concentration (MIC) of chloroform fraction of D. metel L. was
      625.0 microg ml(-1) against all the three species of Aspergillus, i.e. A.
      fumigatus, A. flavus and A. niger, by microbroth dilution and percent spore
      germination inhibition assays. The MIC by disc diffusion assay was observed to be
      12.5 microg disc(-1). The chloroform fraction of D. metel, when investigated for
      potency, turned to be 9.2 times less active than amphotericin B. However, it was
      important to note that the cytotoxicity of chloroform fraction in vitro was 117.8
      times less than amphotericin B.

PMID- 12007711
TI  - Leishmanicidal activity of two canthin-6-one alkaloids, two major constituents of
      Zanthoxylum chiloperone var. angustifolium.
AB  - The crude alkaloidal extract of Zanthoxylum chiloperone stem bark exhibited in
      vitro activity against various strains of Leishmania ssp. at 100 microg/ml. Two
      active major constituents were isolated and identified as canthin-6-one and 5
      methoxycanthin-6-one. The effect of these compounds was also tested in an in vivo
      assay using BALB/c mice infected with Leishmania amazonensis. The mice were
      treated for 5 weeks postinfection with these alkaloids by oral (14 days) or
      intralesional route (4 days) at 10 mg/kg daily. The reference drug, N
      methylglucamine antimonate was administered by subcutaneous injections at 100
      mg/kg for 10 days. Intralesional administration of canthin-6-one reduced the
      parasite burden but not significantly when it was compared with the untreated
      group, while the reference drug reduced by 91% the parasite loads in the lesion.

PMID- 12007712
TI  - Effect of Cassia auriculata Linn. on serum glucose level, glucose utilization by
      isolated rat hemidiaphragm.
AB  - An aqueous leaf extract of Cassia auriculata (C. auriculata) was found to lower
      the serum glucose level in normal rats. Maximum reduction in serum glucose level
      was observed after 4 h at a dose levels of 100, 200, 400 mg/kg body weight of the
      extract. In normal rats the serum glucose level reduction at 4th h was 23% by 100
      mg/kg body weight and 31% by 200 mg/kg body weight. In alloxan-induced diabetic
      rats, chronic administration of the extract significantly reduced the serum
      glucose level from third day to till the end of the experiment. The extract was
      also found to inhibit the body weight reduction induced by alloxan
      administration. Glucose uptake and glycogen deposition studies suggest that C.
      auriculata leaf extract probably has no direct insulin like effect which can
      enhance the peripheral utilization of glucose.

PMID- 12007713
TI  - Hypericum triquetrifolium Turra. Extract exhibits antiinflammatory activity in
      the rat.
AB  - The aim of the present study was to explore the probable antiinflammatory effect
      of Hypericum triquetrifolium Turra. in a rat model of carrageenan induced
      inflammation. Male Wistar rats were treated intraperitoneally with 0.4%
      dimethylsulphoxide (DMSO) (as control group) and H. triquetrifolium extract (25,
      50, 60 mg/kg), 30 min before 0.1 ml 1% carrageenan injection. Paw volume was
      measured before and 1, 2, 3, 4, 5 and 6 h after the injection of carrageenan. The
      results are expressed as the mean+/-s.e. mean and the statistical significance of
      differences between groups was analyzed by One Way Analysis of Variance (ANOVA).
      The intraplantar injection of carrageenan caused a time-dependent paw edema in
      the rat although saline injection caused no swelling. Intraperitoneal
      administration of H. triquetrifolium extract (25, 50, 60 mg/kg) inhibited paw
      swelling dose-dependently at 2, 3, 4, 5 and 6 h after carrageenan injection
      (P<0.05). We can conclude that H. triquetrifolium extract may exert an
      antiinflammatory effect in rats.

PMID- 12007714
TI  - Why do cranberries reduce incidence of urinary tract infections?

PMID- 12007715
TI  - Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation
      signature and strand bias.
AB  - Mutations of p53 and PTCH gene, two candidate tumor suppressor genes for basal
      cell carcinoma (BCC), were screened in 15 cases of sporadic BCCs that developed
      in sun-exposed skin region in a Korean population. p53 and PTCH mutations were
      detected at a frequency of 33 and 40%, respectively, and the mutations were
      predominantly UV-signature transition, C-->T transitions at dipyrimidine sites
      and CC-->TT tandem mutations. In both genes, the most common mutations were
      missense mutations resulting in amino acid substitution, which is different than
      the results from Caucasian BCCs where mutations are frequently predicted to make
      truncated or absent proteins. All mutations, except for one, occurred on the
      nontranscribed strand where is little efficient removal of UV-induced pyrimidine
      dimers relative to the transcribed strand. Loss of heterozygocity (LOH) of 9q22
      for PTCH loci was found in eight of 15 informative cases of BCCs (53%), but none
      of the cases were informative for LOH of 17p13 for p53 loci. Not only do our data
      indicate the key role played by p53 and PTCH in the development of BCCs, these
      findings also suggest that UVB may significantly contribute to BCC tumorigenesis.
      Moreover, molecular epidemiology composed of incidence of p53 and PTCH mutations,
      difference in the type of mutation and repair bias of UV-induced DNA lesions
      might affect the distinct features of BCCs between different racial population.

PMID- 12007716
TI  - A new approach to the evaluation of whitening effect of a cosmetic using computer
      analysis of video-captured image.
AB  - Whitening effects of cosmetics have been evaluated with change of skin
      reflectance of the colorimeter. However, skin color implies Hue (H) and
      Saturation (S) as well as skin reflectance (Value). We have developed a new
      evaluation method of change of skin color using computer analysis of the video
      captured digital image. We have also investigated whitening effects of a new
      whitening cosmetic essence, 'Concentre anti-tache nuit' (CAN; Parfums Christian
      Dior, France), which contained 3% magnesium l-ascorbyl 2-phosphate, on skin color
      of the face in 15 healthy Japanese females. Measurement was performed after 6
      weeks application. Whitening effects were also evaluated with the combination of
      observation and photographs. CAN showed significant improvement in Saturation of
      the forehead and left cheek and Value of the forehead. CAN showed greater
      whitening effects both on the forehead and left cheek in eight (53%) of 15
      subjects with the combination of observation and photographs. These results
      indicated that CAN may have a whitening effect on skin of the face after 6 weeks
      application. This method may be useful to evaluate the whitening effect of
      cosmetics and color change of cutaneous disorders.

PMID- 12007717
TI  - Flow cytometric analysis of IL-4, IL-13 and IFN-gamma expression in peripheral
      blood mononuclear cells and detection of circulating IL-13 in patients with
      atopic dermatitis provide evidence for the involvement of type 2 cytokines in the
      disease.
AB  - Recent studies have shown increased T-helper (Th) 2 cytokine expression and
      decreased IFN-gamma expression in peripheral blood from patients with atopic
      dermatitis (AD). In the present study, we examined the cytokine expression in
      peripheral blood mononuclear cells in patients with AD and tested how the
      cytokine profile correlated with the patients' age, severity and laboratory
      findings. Peripheral blood mononuclear cells obtained from 20 patients with AD
      were stimulated with phorbol 12-myristate 13-acetate and ionomycin, and were
      examined for the frequencies of CD4+ cells expressing IL-4, IL-13 and IFN-gamma
      at the single cell level using intracellular cytokine staining and flow
      cytometry. There was a significant positive correlation between IL-4 and IL-13
      expression in CD4+ cells. Expression levels of both IL-4 and IL-13 in CD4+ cells
      were significantly correlated with peripheral blood eosinophilia. These findings
      suggest that CD4+ cells producing IL-4 and IL-13 play important roles in the
      pathogenesis of AD. IFN-gamma expression did not correlate with either IL-4 or IL
      13 expression, or with blood eosinophilia. We also measured serum levels of IL-13
      in 144 patients with AD using enzyme-linked immunosorbent assay, and found 16
      patients with detectable levels of serum IL-13. IL-13+ patients had significantly
      higher serum IgE levels than IL-13- patients, suggesting a direct association
      between serum levels of IL-13 and IgE. It was also shown that the IL-13+ group
      was significantly younger in age than the IL-13- group, although the implication
      of this finding is not clear at present. The sum of these findings suggested that
      the predominance of Th2 cells and the consequent overexpression of IL-4 and IL-13
      in peripheral blood may be deeply involved in the pathogenetic process of AD.

PMID- 12007718
TI  - Differences in collagen production between normal and keloid-derived fibroblasts
      in serum-media co-culture with keloid-derived keratinocytes.
AB  - Keloids are characterized by the deposition of excessive extracellular-matrix
      collagen by abnormal fibroblasts in response to cutaneous injury. Studies to date
      have largely concentrated on the role of the keloid fibroblast in the
      pathogenesis of this lesion. Recent studies have highlighted the important
      concept of epithelial-mesenchymal interactions in normal skin biology.
      Extrapolating this to keloids in two recent serum-free in vitro studies, we
      demonstrated increased growth and proliferation, as well as induction of keloid
      like collagen secretory characteristics in normal fibroblasts co-cultured with
      keloid-derived keratinocytes. Most fibroblast culture work to date has been
      performed in nutrient and growth factor-rich serum media. To investigate how a
      serum co-culture system might influence epithelial-mesenchymal interactions, [3H]
      proline incorporation was examined in normal and keloid fibroblasts co-cultured
      in serum with keratinocytes derived either from normal skin or keloid tissue.
      Results showed increased [3H] proline incorporation when normal fibroblasts were
      co-cultured with keloid keratinocytes, which was significantly increased when
      keloid fibroblasts were co-cultured with keloid keratinocytes. Taken with
      previous results, this study demonstrates a good correlation between both serum
      and serum-free co-culture systems, and supports the significance of epithelial
      mesenchymal interactions in keloid pathogenesis.

PMID- 12007719
TI  - Comparison of anti 60 and 52 kDa SS-A/Ro antibodies in the pathogenesis of
      cutaneous lupus erythematosus.
AB  - Anti SS-A/Ro antibodies are involved in the pathogenesis of cutaneous lupus
      erythematosus (CLE) in a part through antibody dependent cellular cytotoxicity
      (ADCC). However, it is still obscure which and how anti 60 and anti 52 kDa Ro
      antibodies are involved. To address the issue, we examined both types of anti Ro
      antibodies of sera from patients with systemic LE (SLE) or discoid LE (LE). The
      titer of anti 60 kDa antibody in SLE was significantly much higher than that of
      DLE or control. The positive ratio of DLE showed more higher tendency than
      control, but it was not statistically significant. The similar tendency was
      observed in the titer of anti 52 kDa antibody. An association between the anti 60
      kDa antibody and the anti 52 kDa antibody was statistically significant in SLE
      patients. Although the relative index (RI) was statistically significant in DLE,
      they included many negative sera, which biased the statistics. Both anti 60 kDa
      antibody and anti 52 kDa antibody could induce significant ADCC of ultraviolet B
      (UVB) light-irradiated keratinocytes from neonatal foreskins and/or normal
      adults, in which anti 60 kDa antibody showed higher cytotoxicity than anti 52 kDa
      antibody. The autologous combination studies (keratinocytes and monospecific anti
      60 or anti 52 kDa antibody from patients) suggested anti 60 kDa antibody was more
      potent to induce ADCC activity than anti 52 kDa antibody. Taken together, it is
      likely that anti 60 kDa antibody dependent keratinocyte damage plays more
      significant role in the pathogenesis of SLE skin lesions than anti 52 kDa
      dependent damage. However, both type antibodies seemed to have little
      contribution to the pathogenesis of DLE skin lesion.

PMID- 12007720
TI  - Immunoelectron microscopic analysis of lysosomal deposits in alpha-N
      acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum.
AB  - Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency with angiokeratoma
      corporis diffusum (AKCD) is one of the lysosomal storage diseases.
      GalNAc(alpha))1-O-Ser/Thr (Tn) is theoretically deposited in lysosomes, but
      substances with attached galactose and neuraminic (sialic) acid (T and sialosyl
      Tn, respectively) are excreted in patients' urine. In this study, in two Japanese
      cases we analyzed the material accumulated in lysosomes using immunoelectron
      microscopy with mouse antibodies to Tn, sialosyl Tn and T (Thomsen-Friedenreich)
      antigens in order to find out what substance(s) is really deposited in lysosomes.
      We found that only GalNAc(alpha)1-O-Ser/Thr (Tn) was actually accumulated in
      vacuolated lysosomes of vascular endothelial cells, eccrine sweat gland cells,
      fibroblasts and pericytes. Galactosylation and sialylation of Tn appears to occur
      in cells other than those in the skin. The results suggest that this disease is
      caused by a single enzyme deficiency.

PMID- 12007721
TI  - Functions of the stratum corneum in systemic sclerosis as distinct from
      hypertrophic scar and keloid functions.
AB  - Both transepidermal water loss (TEWL) and skin surface high-frequency conductance
      are functions of the skin barrier. Systemic sclerosis (SSc) and hypertrophic scar
      (HS)/keloid are characterized by abnormal fibrotic changes in the dermis. Since
      the close interrelationship between the epidermis and the dermis has been well
      established, we analyzed the stratum corneum functions of forearm skin in 39 SSc
      patients after assessing the degree of the skin thickening and compared those
      functions with 10 age-matched normal controls. We also analyzed the stratum
      corneum functions of HS or keloid lesions in seven patients using the same
      methods, and compared those functions to adjacent or contralateral normal skin in
      identical patients. Neither the TEWL, nor high-frequency conductance of forearm
      skin in SSc patients were significantly different from those in normal controls.
      There was no correlation between the levels of TEWL or high-frequency conductance
      and the degree of skin thickening in SSc. In HS or keloid conditions, high
      frequency conductance was significantly elevated (42.5+/-8.9 vs. 26.4+/-5.7,
      P<0.001). Although TEWL was elevated, there was no statistical significance
      (48.6+/-39.7 vs. 25.1+/-10.1). Our results revealed that stratum corneum
      functions are distinct between SSc and HS or keloid. This may reflect the various
      natures of dermal changes, which in turn differentiate the functions of the
      stratum corneum in the diseases.

PMID- 12007722
TI  - Confocal laser microscopic observation of glycocalyx production by Staphylococcus
      aureus in vitro.
AB  - We used a scanning confocal laser microscope to study the effects of various
      agents on sugar production by Staphylococcus aureus in vitro. S. aureus cells
      attached to coverslips in Pl-TSB (plasma:tryptic soy broth=1:1) were stained with
      fluorescein isothiocyanate-conjugated concanavalin A (FITC-conA) and were more
      strongly stained over time. We considered that the materials that stained
      positive for FITC-conA consistent with S. aureus cells were sugars, probably
      glycocalyx, produced by the S. aureus cells. Since the cells in the stationary
      growth phase alone were strongly stained with FITC-conA, all S. aureus cells
      attached to the coverslips in Pl-TSB were considered to be in this phase (low
      growth rate). The positive staining for FITC-conA was markedly reduced when
      fibrin was not formed in Pl-TSB with plasmin and sucrose, and was also markedly
      reduced when the fibrin in Pl-TSB was destroyed with plasmin. In conclusion, the
      results of the present study indicate that the existence of fibrin is essential
      for glycocalyx production and biofilm formation of S. aureus cells to aid in the
      attachment of S. aureus cells in vitro, because S. aureus cells attached on
      coverslips and fibrin alone produce glycocalyx. Of the antimicrobial agents
      tested, sulfadiazine silver most strongly inhibited the production of FITC-conA
      positive materials by S. aureus cells at a sub-MIC concentration. Plasmin,
      sucrose, and sulfadiazine silver may be useful topical applications for use on
      clinical dermatology for the prevention and the treatment of staphylococcal
      biofilms. We consider that this simple method is very useful for the detection of
      S. aureus glycocalyx on dermatology field.

PMID- 12007723
TI  - Increased gelatinase activity in systemic sclerosis dermal fibroblast cultures
      with unaltered gelatinase A mRNA expression.
AB  - Gelatinase A is one of the matrix metalloproteinases, the principle enzymes
      degrading extracellular matrix (ECM) and basement membrane components. The aim of
      this study was to study gelatinase expression in systemic sclerosis (SSc).
      Fibroblasts were grown from uninvolved and involved skin of SSc patients and from
      healthy controls. Gelatinase activity was assayed by degradation of tritium
      labeled gelatin. Gelatinase A mRNA was quantitated by competitive reverse
      transcriptase-polymerase chain reaction (RT-PCR). Gelatinase activity was
      significantly increased in both uninvolved and involved SSc cultures. However,
      gelatinase A mRNA was unaltered in both cases. Neither SSc nor control skin
      fibroblasts expressed gelatinase B, indicating that the increased gelatinase
      activity is not due to gelatinase B induction. Gelatinase A is a specific
      basement membrane degrading enzyme, so increased gelatinase activity may be
      related to the pathophysiology of SSc by initiating microvascular damage and
      leakage of substances capable of producing further endothelial cell damage or
      fibroblast activation. Increased gelatinase activity in SSc fibroblasts seems to
      be regulated at translational and/or post-translational level.

PMID- 12007724
TI  - Probucol preserves pancreatic beta-cell function through reduction of oxidative
      stress in type 2 diabetes.
AB  - Oxidative stress is induced under diabetic conditions and causes various forms of
      tissue damage in patients with diabetes. Recently, pancreatic beta-cells have
      emerged as a putative target of oxidative stress-induced tissue damage and this
      seems to explain in part the progressive deterioration of beta-cell function in
      type 2 diabetes. As a step toward clinical trial of antioxidant for type 2
      diabetes, we investigated the possible anti-diabetic effects of probucol, an
      antioxidant widely used as an anti-hyperlipidemic agent, on preservation of beta
      cell function in diabetic C57BL/KsJ-db/db mice. Probucol-containing diet was
      given to mice from 6 to 16 weeks of age. Immunostaining for oxidative stress
      markers such as 4-hydroxy-2-nonenal (HNE)-modified proteins and heme oxygenase-1
      revealed that probucol treatment decreased reactive oxygen species (ROS) in
      pancreatic islets of diabetic animals. Oxidative stress is known to enhance
      apoptosis of beta-cells and to suppress insulin biosynthesis, but probucol
      treatment led to preservation of beta-cell mass and the insulin content.
      According to intraperitoneal glucose tolerance tests, the probucol treatment
      preserved glucose-stimulated insulin secretion and improved glucose tolerance at
      10 and 16 weeks: insulin, 280+/-82 vs. 914+/-238 pmol/l (120 min, at 16 weeks;
      P<0.05); glucose, 44.6+/-2.4 vs. 35.2+/-2.6 mmol/l (120 min, at 16 weeks;
      P<0.05). Thus, our present observations demonstrate the potential usefulness of
      probucol for treatment of type 2 diabetes.

PMID- 12007725
TI  - The effect of in vitro fibroblast growth factors on cell proliferation in
      pancreas from normal and streptozotocin-treated rats.
AB  - Fibroblast growth factors (FGFs) are potent mitogens for a wide variety of cells.
      In the present study we examined the potential morphogenic activities of the
      growth factors FGF1, FGF2 and FGF7, and cellular processes underlying
      morphogenesis, in pancreatic cells from streptozotocin diabetic newborn rats. The
      pancreases from control and diabetic newborn rats were microdissected and
      cultured in the presence of different doses of FGF1, 2 and 7 for 48 h. An
      additional incubation for 24 h was undertaken in the presence of bromo
      deoxyuridine. The effect of the FGFs on bromo-deoxyuridine incorporation was
      analysed by means of immunocytochemistry. The most prominent stimulatory effect
      was found after application of FGF2 and 7 at a dose of 100 ng/l in endocrine and
      exocrine cells of diabetic rats. It is concluded that FGF2 and 7 might act as
      putative key-signalling molecules in the differentiation of pancreatic cells.

PMID- 12007726
TI  - Glycemic response during exercise after administration of insulin lispro compared
      with that after administration of regular human insulin.
AB  - To examine the glycemic response during exercise after administration of short
      acting insulin lispro, we compared changes in plasma glucose concentrations
      during exercise performed by patients with diabetes after the administration of
      either insulin lispro or regular human insulin. Seven patients with diabetes (two
      with type 1 and five with type 2) participated in this study. Each of the insulin
      depleted subjects received the same number of units of either insulin lispro or
      regular human insulin, delivered subcutaneously to the abdomen. The next day,
      each subject received a similar injection of the solution not previously
      administered. After each injection, the subjects were fed a standard meal of
      approximately 9 kcal/kg body weight. One hour after eating the test meal, the
      subjects performed 30 min of cycle ergometer exercise at 50% maximal oxygen
      uptake. Plasma glucose, insulin, glucagon, growth hormone (GH), and catecholamine
      concentrations were then measured at specific intervals. Insulin concentrations
      were higher and peaked earlier after administration of insulin lispro than after
      administration of regular human insulin. The length of time, needed to reach
      minimum plasma glucose concentration after exercise was begun, was significantly
      shorter after administration of insulin lispro, and the percentage of plasma
      glucose decrease induced by exercise relative to the peak concentration was
      significantly greater. No differences were found in the concentration changes of
      counterregulatory hormones between the insulin lispro data and the regular human
      insulin data. Compared with regular human insulin, insulin lispro induces a more
      rapid and greater decrease in plasma glucose concentration during exercise
      because of its faster absorption.

PMID- 12007727
TI  - Diabetes and impaired glucose tolerance in Aboriginal Australians: prevalence and
      risk.
AB  - The prevalence and risk of having impaired glucose tolerance (IGT) and diabetes
      was estimated relative to body mass index (BMI) among Australian Aboriginal
      people. A stratified analysis was undertaken of community screening data.
      Measures included fasting and 2-h glucose concentrations, and BMI (five strata:
      <22, 22-24.9, 25-29.9, 30-34.9 and >/=35 kg/m(2)). Age was stratified into three
      groups: 15-34.9, 35-44.9, and >/=45 years. Participants were men and women, ages
      15-94 years (n=2626). The prevalence of IGT and diabetes, respectively, adjusted
      for age and BMI, was 139 and 142 cases/1000 persons among men, and 157 and 152
      cases/1000 persons among women. Odds ratios (95% CI) for IGT and diabetes for
      increasing BMI strata >/=22 kg/m(2) ranged from 1.7 (1.0 to 2.9) to 5.1 (2.4
      10.5) for IGT, and from 2.0 (1.2-3.5) to 6.1 (3.3-11.1) for diabetes. For IGT and
      diabetes, across genders, the population attributable risk percentages (95% CI)
      for BMI >/=22 kg/m(2) were 34.1% (26.2-41.9%) for IGT, and 46.4% (38.5-54.5%) for
      diabetes. Diabetes and IGT have reached epidemic proportions among Australian
      Aboriginal people. An urgent need exists for programmes to reduce the prevalence
      of diabetes risk factors, especially BMI of 22 kg/m(2) or more, a limit lower
      than advocated for Euro-American populations.

PMID- 12007728
TI  - Incidence of diabetic nephropathy in Type 1 diabetic patients in Spain: 'Estudio
      Diamante'.
AB  - AIMS: To determine the prevalence and the incidence of diabetic nephropathy in
      Type 1 diabetes mellitus in Spain and to investigate the risk factors for the
      development of microalbuminuria. METHODS: One thousand five hundred and two
      patients with Type 1 diabetes mellitus were prospectively followed in 15 hospital
      diabetes outpatient clinics in Spain. Blood pressure, body weight, HbA(1c), total
      cholesterol, HDL-cholesterol, triglycerides, plasma creatinine and urinary
      albumin excretion (UAE) were determined every 3-5 months. RESULTS: A total of
      1225 patients (624 males and 601 females), age 30.7+/-9.3 years with diabetes
      duration of 14.1+/-9.1 years completed 4.3 (4.0-5.1) years of follow-up. At
      baseline 14.2 (95% CI 12.3-16.3)% of patients had microalbuminuria, 5.1 (3.9
      6.4)% macroalbuminuria and 3.4 (2.5-4.6)% kidney failure. During follow-up the
      annual incidence of microalbuminuria was 2.7 (2.2-3.2)%. In a multiple logistic
      regression analysis the predictors of progression to microalbuminuria were
      initial UAE, HbA(1c), diabetes duration, smoking, and HDL-cholesterol <0.9
      mmol/l. CONCLUSIONS: The prevalence and incidence of diabetic nephropathy in
      Spain are comparable to data obtained in similar studies carried out in other
      countries. The development of microalbuminuria is associated not only with
      glycaemic control and hypertension, but also to the control of other risk factors
      such as dyslipaemia and smoking.

PMID- 12007729
TI  - Insensate versus painful diabetic neuropathy: the effects of height, gender,
      ethnicity and glycaemic control.
AB  - AIMS/HYPOTHESIS: To study similarities and differences between people with
      insensate or painful diabetic peripheral neuropathy, particularly in relation to
      height, gender, ethnicity and glycaemic control. METHODS: We studied
      prospectively 2610 patients with Type 2 diabetes attending our Diabetes Centre.
      Subjects were compared according to degree of sensory loss, and presence or
      absence of neuropathic pain. The effects of gender and ethnicity were evaluated
      by studying patients in different height bands. RESULTS: Insensate neuropathy and
      painful neuropathy was present in 11.4 and 3.3% of subjects, respectively. Age,
      duration of diabetes, height, vibration perception and HbA(1c) (P<0.0001) were
      independent determinants of insensate neuropathy, whereas only duration of
      diabetes and vibration perception (P<0.0001) were predictive of pain. There was
      more insensate neuropathy in males (OR 1.9) and anglo-celtics (OR 1.4) but
      stratification by height showed that these effects were due to height. Height has
      no influence on the development of pain. CONCLUSIONS: There is significant
      overlap but also considerable dichotomy in the two major forms of diabetic
      sensory peripheral neuropathy. The insensate type is more explainable by
      duration, degree of hyperglycaemia and length of peripheral nerves, factors that
      are likely to reflect severity of underlying structural nerve damage. Glycaemic
      control was not a predictor of painful neuropathy.

PMID- 12007730
TI  - Moderate alcohol consumption is associated with lower risk for incident diabetes
      and mortality: the Hoorn Study.
AB  - In the present study we examined the association between baseline alcohol
      consumption and 10-year mortality in subjects with normal and abnormal glucose
      levels (diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance
      (IGT)). Furthermore, we assessed the 6-year cumulative incidence of diabetes in
      categories of alcohol consumption. In the Hoorn Study, which started in 1989,
      alcohol intake was assessed by questionnaire in 2393 subjects who were
      subsequently categorised into four groups of alcohol consumption (non-drinkers,
      up to 10 g per day, 10-30 and >or=30 g per day). Glucose tolerance status by oral
      glucose tolerance test was classified according to the WHO-1999 diagnostic
      criteria. Subjects who drank up to 10 g per day of alcohol had the lowest
      mortality risk. The age- and sex-adjusted mortality risks for non-drinkers were
      1.55 (1.04-2.32) for subjects with normal glucose levels and 1.72 (1.05-2.82) for
      subjects with abnormal glucose levels. The risk of diabetes was also lowest for
      subjects who consumed up to 10 g per day: 8.0 versus 12.9% for non-drinkers
      (P<0.05). Higher alcohol intakes were associated with increasing risks for
      mortality and diabetes. Adjustment for classical cardiovascular risk factors and
      other lifestyle variables did not materially affect the estimates. In conclusion,
      moderate alcohol consumption was associated with a lower risk for mortality and
      diabetes.

PMID- 12007731
TI  - Influence of type 2 diabetes mellitus on cardiovascular disease mortality:
      findings from the Hawaii-Los Angeles-Hiroshima study.
AB  - The present study addressed whether diabetes mellitus was a strong risk factor
      for cardiovascular disease (CVD) death. Between 1976 and 1984, 927 (404 men)
      Japanese-Americans in Hawaii aged 40-79 years participated at baseline
      examination including a 75 g oral glucose tolerance test. Diabetes was defined as
      fasting serum glucose >or=140 mg/dl, 2 h postload glucose >or=180 mg/dl, or the
      use of drugs for diabetes. Causes of death were classified by ICD-9 codes on the
      reports from the Hawaii State Public Health Bureau. Until 1994, 178 individuals
      suffered death; 81 were attributed to CVD and 43 to coronary heart disease (CHD).
      The age-adjusted and coronary risk factors-adjusted relative risks for CHD and
      CVD mortality were significant for diabetes both in men and women. The impact of
      diabetes on CHD mortality was greater for women. However, no gender difference in
      the contribution of diabetes to fatal CVD was observed. Serum fasting glucose
      levels tended to be associated with CHD death and were associated with CVD death
      in diabetic subjects. In conclusion, diabetes is a strong independent risk factor
      for CVD mortality in Japanese-American men and women. Hyperglycemia is associated
      with CVD mortality in diabetic subjects.

PMID- 12007733
TI  - Matrix metalloproteinase disruption of the extracellular matrix and cardiac
      dysfunction.
AB  - In the heart, collagens are the major extracellular matrix (ECM) protein. The
      fibrillar collagens of the heart surround and interconnect myocytes and muscle
      fibers to provide for muscle fiber and myocyte alignment which imparts mechanical
      support to the myocardium and governs tissue stiffness. Loss of collagen fibrils
      and struts are said to lead to myocyte slippage, ventricular dilation, and
      progressive contractile dysfunction. Failed human hearts examined either at
      autopsy or explantation invariably exhibit alterations of the ECM primarily due
      to changes in collagen. Modulation of the balance between matrix synthesis and
      degradation is important in the process of ventricular remodeling and in the
      pathophysiology of chronic heart failure. Support for the importance of the ECM
      and activity of matrix metalloproteinases (MMP) in the development of chronic
      heart failure has been demonstrated both in animal models of heart disease and in
      humans. A causative role for the ECM in this process was recently revealed in
      experiments using a transgenic mouse model that expresses the specific collagen
      degrading enzyme, MMP-1, in the heart. These studies demonstrated that chronic
      expression of MMP-1 leads to dynamic changes in the heart and ultimately results
      in systolic dysfunction. Multiple studies in animal models have also shown that
      inhibition of MMP activity in animal models of heart failure have attenuated the
      onset of left ventricular dilatation. Future studies will determine whether
      inhibition of MMP activity improves morbidity and mortality in patients with
      heart failure.

PMID- 12007734
TI  - Interactions of intercellular adhesion molecule-1 with fibrinogen.
AB  - The binding of plasma protein fibrinogen (Fg) to intercellular adhesion molecule
      1 (ICAM-1) on endothelial cells mediates the attachment of leukocytes and
      platelets that may result in vascular occlusion. Fg:ICAM-1 interactions elicit an
      array of effects that could have implications in vascular pathology and
      inflammation. ICAM-1 expression is regulated during inflammation and upon Fg
      binding. The mechanistic model presented provides a framework to delineate the
      consequences of Fg binding to ICAM-1.

PMID- 12007735
TI  - VEGF gene delivery for treatment of ischemic cardiovascular disease.
AB  - There are increasing numbers of patients with ischemic myocardial disease not
      amenable to traditional methods of revascularization. These patients may benefit
      from new research into the use of naturally occurring angiogenic compounds, such
      as vascular endothelial growth factor (VEGF) for re-establishing blood flow into
      regions of hibernating myocardium. Animal studies and human clinical trials
      evaluating VEGF demonstrate increases in myocardial perfusion after treatment,
      with some patients reporting improvement in anginal symptoms. Further research
      into the ideal form of VEGF therapy (protein, plasmid, or adenoviral) and
      delivery method (intracoronary, intramyocardial, or epicardial) seems justified.

PMID- 12007736
TI  - The use of ex vivo gene transfer based on muscle-derived stem cells for
      cardiovascular medicine.
AB  - Cell transplantation is a potential therapy for patients suffering from
      congestive heart failure. Many cell types have been experimentally tested for
      their ability to improve cardiac function. In this review, we discuss the
      potential of cell transplantation into the heart using various cell sources and
      introduce an attractive new cell source: Muscle-derived stem cells (MDSCs) are
      capable of delivering therapeutic genes and potentially differentiating toward a
      cardiomyocyte lineage within an injected heart. MDSCs are an attractive,
      alternate cell source because in addition to being multipotent (i.e., capable of
      differentiating into various lineages), they are easily accessible via simple
      biopsy of the patient's own muscle. This review will describe the isolation and
      unique characteristics of MDSCs and outline their potential use in regenerative
      medicine.

PMID- 12007737
TI  - The effects of altered apolipoprotein A-I structure on plasma HDL concentration.
AB  - Approximately 46 human apolipoprotein A-I (apoA-I) coding sequence mutations have
      been reported to date. Roughly half of these mutations are associated with lower
      than average plasma concentrations of high-density lipoprotein (HDL) apoA-I.
      Mutations associated with low HDL apoA-I concentrations fall into two main
      categories: those which poorly activate the enzyme lecithin:cholesterol
      acyltransferase (LCAT) and those associated with amyloidosis. These
      phenotypically distinct groups of mutations are uniquely localized in different
      regions of the apoprotein sequence. Mutations associated with abnormal LCAT
      activation are located within repeats 5, 6, and 7, corresponding to amino acids
      121 to 186, while many of the mutations found in amyloid deposits are clustered
      at the amino terminus of the protein, namely residues 1 to 90. These observations
      strongly support the idea that the tertiary structure of apoA-I determines its
      intravascular fate and ultimately the steady state concentration of plasma HDL.

PMID- 12007738
TI  - Role of placenta growth factor in cardiovascular health.
AB  - Placenta growth factor (PlGF), a member of the cysteine-knot family, is an
      angiogenic protein. The PlGF gene has been conserved across different species of
      the animal kingdom. It is expressed primarily in the placenta, especially in the
      later stages of gestation. PlGF expression is upregulated during pathological
      conditions such as ischemia of the heart and myocardial infarction. It is now
      known that PlGF can modulate the activity of vascular endothelial growth factor,
      the most potent of all angiogenic inducers and hence makes it an attractive
      target for therapeutic strategies. Recent structural studies on different
      isoforms of PlGF promise to reveal important topological and molecular details of
      these proteins that may be of potential use in the design of effective small
      molecule inhibitors to combat pathological angiogenesis.

PMID- 12007739
TI  - Mechanisms of lipoapoptosis: implications for human heart disease.
AB  - Accumulation of long-chain fatty acids in the heart has been proposed to play a
      role in the development of heart failure and diabetic cardiomyopathy. Several
      animal models with increased cardiomyocyte lipid accumulation suggest a link
      between the accumulation of lipid, cardiomyocyte cell death and the development
      of cardiomyopathy. In this review, we discuss the mechanism through which fatty
      acid accumulation may contribute to the development or progression of heart
      failure by initiation of apoptotic cell death. Long-chain saturated fatty acids
      induce apoptosis through a mechanism involving the generation of reactive
      intermediates. Reactive intermediate production occurs in concert with de novo
      ceramide synthesis, but ceramide production is not required for cell death.
      Cardiomyocyte dysfunction and death from reactive intermediates generated by long
      chain saturated fatty acids may contribute to the pathogenesis of human heart
      disease.

PMID- 12007740
TI  - Regulation of ROMK channels by protein tyrosine kinase and tyrosine phosphatase.
AB  - Renal outer medulla K (ROMK) channels play an important role in K recycling in
      the thick ascending limb and in K secretion in the cortical collecting duct.
      ROMK1, a member of the ROMK family, has been shown to be a substrate for protein
      tyrosine kinase (PTK). The tyrosine phosphorylation of ROMK channels increases
      with low dietary K intake and decreases with high dietary K intake. Moreover, the
      stimulation of tyrosine phosphorylation of ROMK1 channels decreases the number of
      K channels by facilitating endocytosis. In contrast, the stimulation of tyrosine
      dephosphorylation increases the number of ROMK1 channels in the cell membrane by
      enhancing membrane insertion. PTK and tyrosine phosphatase-induced regulation of
      ROMK1 channels play a key role in mediating the effect of the dietary K intake on
      renal K secretion.

PMID- 12007741
TI  - Memory processes governing amphetamine-induced psychomotor sensitization.
AB  - We investigated how, under certain circumstances, the expression of psychomotor
      sensitization comes to be context-specific. Rats that had previously sustained 6
      hydroxydopamine-induced unilateral dopamine depletion received repeated
      injections of d-amphetamine (AMPH) or saline in group-specific environments, and
      rotational behavior was measured as an index of psychomotor activation. Following
      these treatments some groups were given electroconvulsive shock (ECS), when
      memories of the drug experience were reactivated (and therefore vulnerable to
      disruption), in order to produce retrograde amnesia. Animals given an AMPH
      challenge in the environment in which they received drug treatments (Paired)
      expressed robust sensitization. Animals given an AMPH challenge in a context that
      was never paired with drug administration (Unpaired) did not express
      sensitization. A saline challenge in the AMPH paired context produced a
      conditioned rotational response (CR). ECS had no effect in Control animals, no
      effect on the expression of sensitization in Paired animals, and no effect on the
      expression of the CR in Paired animals. However, ECS did affect Unpaired groups:
      unlike Unpaired animals given sham ECS, Unpaired animals given ECS expressed
      robust sensitization. Thus, without ECS, the expression of sensitization must
      have been suppressed in the Unpaired animals (who had the same drug history as
      Paired animals), and ECS released this otherwise suppressed sensitization. Based
      on these and other findings, we propose that three memory mechanisms regulate
      context-specificity of AMPH sensitization: (1) Repeated drug administration
      induces sensitization of the neural substrate that mediates the unconditional
      response (UR) to the drug, a form of non-associative learning; (2) An inhibitory
      process can block the expression of neural sensitization in contexts where the
      drug is not expected, a process we speculate may involve a form of inhibitory
      occasion-setting; (3) An excitatory conditioned response (CR) can amplify the
      sensitized response in a context where the drug is expected. It is suggested that
      the ability of drug-associated contexts to modulate the expression of neural
      sensitization via occasion-setting may combine with the ability of a drug
      associated context to produce conditioned responses, together providing powerful
      associative control over not only behavioral sensitization, but in addicts, over
      craving and relapse.

PMID- 12007742
TI  - Deficits in impulse control associated with tonically-elevated serotonergic
      function in rat prefrontal cortex.
AB  - Converging lines of evidence suggest that dysfunction of brain serotonergic
      systems may underlie impulsive behavior. However, the nature of this deficit
      remains poorly understood because indirect indices of serotonin (5-HT) function
      are often used in clinical and experimental studies. In this investigation we
      measured 5-HT release directly in the prefrontal cortex of rats using in vivo
      microdialysis during performance of a visual attentional task. A number of
      performance measures were taken, including the number of premature responses made
      during the inter-trial interval before the onset of the visual discriminanda.
      This form of behavioral disinhibition was defined as impulsive, after.
      Lengthening the inter-trial interval increased the sensitivity of the task for
      detecting impulsive tendencies. Cortical levels of 5-HT and its metabolite 5-HIAA
      remained at pre-task levels over 1 h of task performance. By contrast, levels of
      dopamine (DA) and its metabolite DOPAC increased during this period. Regression
      analysis established a positive relationship between premature (impulsive)
      responses and 5-HT efflux, both under basal (r = 0.49) and task-related (r =
      0.42) conditions (n = 31). No such relationship was found for prefrontal levels
      of DA. However, post-mortem analysis revealed that animals that were more
      impulsive had a higher turnover of DA in anterior cingulate, prelimbic and
      infralimbic cortices but no detectable abnormalities in 5-HT function. These data
      indicate that elevated 5-HT release in the prefrontal cortex may underlie
      deficits in impulse control on this task. Additionally, DA dysfunction in this
      region may be another, possibly independent, trait marker of impulsivity.

PMID- 12007743
TI  - Alcohol self-administration in two rat lines selectively bred for extremes in
      anxiety-related behavior.
AB  - According to the tension reduction hypothesis, individuals with an elevated
      anxiety level may be more sensitive to the anxiolytic effects of alcohol and may,
      therefore, have a higher predisposition to consume alcohol. To examine this
      hypothesis, we studied the drinking behavior as well as the sensitivity to the
      anxiolytic effect of alcohol in two rat lines that were bred and selected for
      differences in anxiety-related behavior on the elevated plus-maze: the extremely
      anxious HAB (high anxiety-related behavior) and the non-anxious LAB (low anxiety
      related behavior) lines. Alcohol self-administration and the occurrence of an
      alcohol deprivation effect were studied in female and male HAB and LAB rats in a
      free-choice, 4-bottle home cage paradigm. The sensitivity of HAB and LAB rats to
      the anxiolytic effect of alcohol was assessed by testing their behavior on the
      elevated plus-maze after an acute application of ethanol. During the first days
      of voluntary ethanol drinking, the ethanol intake and preference of female LABs
      was significantly higher than that of female HABs. Although not statistically
      significant, the same trend could be seen in male LABs. Moreover, male as well as
      female LAB but not HAB rats showed a significant alcohol deprivation effect after
      abstinence. There were no differences when saccharin was presented to naive
      animals, indicating that the different ethanol drinking behavior of HAB and LAB
      rats does not represent a general difference in the consumption of new liquids.
      Application of ethanol resulted in an anxiolytic effect in HAB but not in LAB
      rats on the elevated plus-maze. In summary, increased inborn anxiety and
      voluntary ethanol consumption of HAB and LAB rats were correlated to some extent;
      however, this relationship was a negative one. It is concluded that, although
      such a relationship might exist in some individuals, increased levels of inborn
      anxiety and alcohol consumption are not necessarily related.

PMID- 12007744
TI  - Local dopaminergic modulation of the motor activity induced by N-methyl-D
      aspartate receptor stimulation in the ventral hippocampus.
AB  - Dopaminergic neurotransmission has been implicated in the motor activating
      effects induced by the local infusion of NMDA in the ventral hippocampus (VH).
      The nucleus accumbens and the ventral tegmental area (VTA) have been proposed to
      be the main loci where dopamine is acting as a positive modulator of the VH NMDA
      receptor-mediated motor activating effects. However, the existence of a
      relatively high dopamine innervation and dopamine receptor density in the VH
      suggests the possibility of local dopamine/NMDA receptor interactions. This
      hypothesis was tested by studying the effects of the bilateral local VH infusion
      of NMDA (0.05, 0.1, 0.5 and 1.0 microg/side), the dopamine D1/D5 receptor
      antagonist SCH 23390 (1 microg/side) and the dopamine D2 receptor antagonist
      raclopride (1 and 5 microg/side). Neither SCH 23390 nor raclopride induced any
      significant change in motor activity compared with the vehicle control group, but
      both compounds significantly antagonized the motor activation induced by NMDA.
      SCH 23390 (1 microg/side) was more potent that raclopride (minimal effective
      dose: 5 microg/side). These results demonstrate the existence of a strong tonic
      facilitating effect of dopamine, acting preferentially at dopamine D1/D5
      receptors, on NMDA receptor-mediated effects in the VH.

PMID- 12007745
TI  - Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim
      assay in rats.
AB  - The present study examined the effect of opioid receptor agonists in the rat
      forced swim assay. The delta-opioid receptor agonists SNC80 ((+)-4-[(alpha R)
      alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N
      diethylbenzamide) and (+)BW373U86 ((+)-[1(S*),2 alpha,5 beta]-4-[[2,5-dimethyl-4
      (2-propenyl)-1-piperazinyl] (3-hydroxyphenyl)methyl]-N,N-diethyl-benzamide
      dihydrochloride) produced a decrease in immobility indicating an antidepressant
      like effect. At antinociceptive doses, neither the kappa-opioid selective agonist
      CI977 (5R-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolidinyl-1
      oxaspiro[4,5]dec-8-yl]-4-benzofuranacetamide) showed a change in immobility that
      was identifiable by dose, nor were changes in immobility seen with morphine. A
      delta-opioid mechanism of action in the forced swim assay was likely since
      naltrindole prevented the effects of both delta-agonists. When compared to
      desipramine and fluoxetine, SNC80 was more active with a single dose whereas both
      desipramine and fluoxetine produced greater effects with subchronic dosing (3
      doses). All three compounds were active when administered before the initial swim
      exposure. SNC80 was, however, more effective following a single dose than by
      subchronic administration demonstrating both a fast onset of activity and
      potential tolerance. Thus, delta-agonists differ from typical antidepressants in
      the forced swim assay.

PMID- 12007746
TI  - Effect of bilateral 6-hydroxydopamine lesions of the medial forebrain bundle on
      reaction time.
AB  - Overt symptoms of Parkinson's disease do not manifest themselves until there is a
      substantial loss of the dopaminergic nigrostriatal projection. However, as
      neuroprotective strategies are developed, it will be essential to detect the
      disease in its preclinical phase. Performance on conditioned reaction time tasks
      is known to be impaired by extensive 6-hydroxydopamine-induced lesions of the
      nigrostriatal dopamine pathway. However, the effect of smaller lesions on a
      reaction time task has not been systematically assessed. We, therefore, used this
      test to examine behavioral deficits as a function of striatal dopamine loss. When
      injected at doses that produced striatal DA depletion <50%, 6-hydroxydopamine
      infused in the medial forebrain bundle produced no reliable impairment in the
      reaction time task. Higher doses producing > or = 60% DA depletion in the
      striatum produced a decrease in the percent correct responding throughout the 5
      week testing period and akinetic deficits expressed by an increase in delayed
      responding. In addition, larger DA depletions (> or = 95%) profoundly altered
      motor control with decreases in percent correct responses, increases in delayed
      responses and increases in reaction time. These results suggest that reaction
      time may be a relatively sensitive measure of preclinical or subtle deficits,
      although it might be even more useful in quantitating the severity of depletion
      once overt deficits or symptoms appear and has the advantage of measuring such
      deficits over time to follow recovery of function. Furthermore since reaction
      time deficits required extensive loss of dopamine, these results are consistent
      with a predominant role of extrasynaptic dopamine in the mediation of relatively
      skilled motor tasks.

PMID- 12007747
TI  - Clozapine and haloperidol reinstate latent inhibition following its disruption
      during amphetamine withdrawal.
AB  - Latent inhibition (LI) is a behavioral phenomenon whereby repeated exposure to a
      non-reinforced stimulus retards subsequent conditioning to that stimulus.
      Deficits in LI may reflect an inability to ignore irrelevant stimuli and are
      studied as a model of the cognitive/attentional abnormalities found in
      schizophrenia. We recently determined that pretreatment with escalating doses of
      the indirect dopamine agonist amphetamine (AMPH; 3 daily injections ip, 1-5
      mg/kg, over 6 days) disrupts LI in rats tested in a 2-way active avoidance
      paradigm during withdrawal. In the present study, we evaluated the effects of the
      atypical neuroleptic clozapine and the typical neuroleptic haloperidol on the
      expression of LI on day 4 of AMPH withdrawal. Neuroleptic injections were given
      either 45 min prior to each of two tone preexposure sessions and a subsequent
      tone-shock avoidance test session, or only prior to the test session. As
      expected, saline-injected control groups showed LI during the test session, as
      reflected by significantly reduced avoidance in tone preexposed vs. non
      preexposed rats. In contrast, animals pretreated with escalating doses of AMPH
      did not show LI, due to the improved avoidance of the preexposed animals. Both
      haloperidol (0.03 mg/kg) and clozapine (5 mg/kg) largely reversed the disruptive
      influence of AMPH on LI regardless of whether these drugs were administered prior
      to both preexposure and test sessions or only prior to the test session. These
      results provide pharmacological validation for an AMPH withdrawal model of
      schizophrenic symptoms.

PMID- 12007748
TI  - Hypothalamic-pituitary-adrenocortical (HPA) axis response and biotransformation
      of oral naltrexone: preliminary examination of relationship to family history of
      alcoholism.
AB  - We examined HPA axis response to 50 mg oral naltrexone compared with placebo in
      17 healthy male and female nonalcoholic subjects, approximately half of whom had
      a positive family history of alcoholism (FH+) and half of whom who did not (FH-).
      Mood response and naltrexone biotransformation were also examined at various
      intervals. Subjects participated in two morning test sessions (50 mg naltrexone
      or identical placebo pill) after an overnight stay in the Rockefeller University
      GCRC. For the total sample, ACTH and cortisol significantly increased after
      naltrexone compared with placebo (p <.05). Secondary analyses showed the FH+
      subgroup had a different pattern of response over time compared with the FH-
      subgroup, with heightened ACTH and cortisol, and decreased vigor ratings, during
      naltrexone (p <.05). The results demonstrate that orally administered naltrexone
      acutely disinhibits the HPA axis, and that individuals with an assumed greater
      biological vulnerability to addiction, by virtue of familial alcoholism, had
      altered regulation of the HPA axis in part under the control of the endogenous
      opioid system. 166 words.

PMID- 12007749
TI  - Association between a polymorphism of the 5-HT2C receptor and weight loss in
      teenage girls.
AB  - Receptors of the 5-HT2C subtype are assumed to be involved in the influence of
      serotonin on food intake. A polymorphism in the coding region of the gene for
      this receptor, resulting in a cysteine to serine substitution, has been reported.
      Fifty-seven somatically healthy teenage girls displaying weight loss and 91
      normal-weight girls of the same age, all recruited by means of a population-based
      screening study, were compared with respect to this polymorphism. Subjects in the
      weight loss group displayed a higher frequency of the serine allele than those in
      the comparison group (23.7% vs. 7.7%, p =.0001). Seventy-two percent of the
      weight loss girls fulfilled the diagnostic criteria of anorexia nervosa, whereas
      28% did not; when these two groups were separately analyzed, both differed
      significantly from controls with respect to serine allele frequency. The results
      support the notion that the studied gene may be involved in the regulation of
      food intake in young women.

PMID- 12007750
TI  - Delusional disorder: molecular genetic evidence for dopamine psychosis.
AB  - Since delusional disorder is characterized by mono-symptomatic paranoid symptoms,
      it can be a good clinical model for investigating the dopaminergic mechanism
      responsible for paranoid symptoms. We examined neuroleptic responses, plasma
      homovanillic acid (pHVA) and genes of the dopamine receptor (DR) and its
      synthesizing enzyme (tyrosine hydroxylase: TH) in patients with delusional
      disorder and compared them with those of schizophrenic patients and healthy
      controls. RESULTS: (1) A relatively small dose of haloperidol was more effective
      for delusional disorder than for schizophrenia. (2) The pretreatment level of
      pHVA was higher in patients with persecution-type, but not in those with jealousy
      type delusional disorder, compared with age- and sex-matched controls. This
      increased pHVA level was decreased eight weeks after successful haloperidol
      treatment. (3) The genotype frequency of the DRD2 gene Ser311Cys was
      significantly higher in patients with persecution-type delusional disorder (21%),
      compared with schizophrenic patients (6%) or controls (6%). (4) Patients
      homozygous for the DRD3 gene Ser9Ser had higher pretreatment levels of pHVA than
      those heterozygous for Ser9Gly. (v) A significant positive correlation was found
      between the polymorphic (TCAT)(n) repeat in the first intron of the TH gene and
      pretreatment levels of pHVA in delusional disorder. We suggest that delusional
      disorder, especially the persecution-type, includes a "dopamine psychosis," and
      that polymorphism of the DRD2, DRD3 and/or TH gene is part of the genetic basis
      underlying the hyperdopaminergic state that produces paranoid symptoms. Further
      studies on a large sample size are required.

PMID- 12007751
TI  - Effects of smoking marijuana on brain perfusion and cognition.
AB  - The effects of smoking marijuana on regional cerebral blood flow (rCBF) and
      cognitive performance were assessed in 12 recreational users in a double-blinded,
      placebo-controlled study. PET with [(15)Oxygen]-labeled water ([(15)O]H(2)O) was
      used to measure rCBF before and after smoking of marijuana and placebo
      cigarettes, as subjects repeatedly performed an auditory attention task. Smoking
      marijuana resulted in intoxication, as assessed by a behavioral rating scale, but
      did not significantly alter mean behavioral performance on the attention task.
      Heart rate and blood pressure increased dramatically following smoking of
      marijuana but not placebo cigarettes. However, mean global CBF did not change
      significantly. Increased rCBF was observed in orbital and mesial frontal lobes,
      insula, temporal poles, anterior cingulate, as well as in the cerebellum. The
      increases in rCBF in anterior brain regions were predominantly in "paralimbic"
      regions and may be related to marijuana's mood-related effects. Reduced rCBF was
      observed in temporal lobe auditory regions, in visual cortex, and in brain
      regions that may be part of an attentional network (parietal lobe, frontal lobe
      and thalamus). These rCBF decreases may be the neural basis of perceptual and
      cognitive alterations that occur with acute marijuana intoxication. There was no
      significant rCBF change in the nucleus accumbens or other reward-related brain
      regions, nor in basal ganglia or hippocampus, which have a high density of
      cannabinoid receptors.

PMID- 12007752
TI  - Surgically implantable long-term antipsychotic delivery systems for the treatment
      of schizophrenia.
AB  - Non-adherence with medication remains a major correctable cause for poor outcome
      in schizophrenia. We describe a surgically implantable preparation of haloperidol
      with the aim that patients will have superior outcomes with improved medication
      adherence from implants. In contrast to depot formulations, implantable pellets
      could last many months, providing symptomatic improvement for periods of time
      never before possible. Additionally, in the event of unacceptable side effects,
      implants could be removed, offering a degree of reversibility not available with
      depot formulations. A surgically-implantable formulation of haloperidol has been
      created using biodegradable polymers. Implants have been characterized for in
      vitro kinetics, as well as in-vivo bioactivity in rodents. Haloperidol implants
      demonstrate steady release of drug for 5 months. Animals treated with haloperidol
      implants display increased striatal D2 receptor expression as well as increased
      apomorphine stimulated locomotion. Surgically-implantable formulations are a
      viable approach to provide long-term delivery of antipsychotic medications to
      patients with psychotic disorders.

PMID- 12007753
TI  - The ventilatory response to cholecystokinin tetrapeptide in healthy volunteers.
AB  - The cholecystokinin (CCK) system, which has been shown to interact with both the
      panicogenic and respiratory systems, provides an interesting mechanism to further
      evaluate the central chemoreceptor and its effect on panic attack sensitivity.
      Intravenous CCK, a naturally occurring neuropeptide in the brain, has been found
      to induce the emotional and somatic symptoms of panic in both Panic Disorder (PD)
      and Normal Control (NC) subjects in a dose-dependent and reproducible fashion. To
      induce these effects, lower doses of intravenous CCK are required in the PD
      patients, relative to the NC subjects potentially suggesting that endogenous
      alterations in the CCK system may be contributing to the development of PD.
      Intravenous administration of CCK-4 in association with panic also results in
      subjective dyspnea, that is, diminution in vital capacity without an effect on
      the respiratory resistance. CCK-4 also causes a significant increase in tidal
      volume and minute ventilation but has no effect on breathing frequency. These
      observations suggest that a CCK-B receptor agonist may be acting as a respiratory
      stimulant, exerting its effect on anxiety through a direct effect on respiration.
      This study represents an examination of the specific effects of CCK-4 on the
      central chemoreceptor response. The study used a modified rebreathing technique,
      which accurately measures the ventilatory response to carbon dioxide in terms of
      both threshold and sensitivity. This technique requires the subject to rebreathe
      from a bag containing a hyperoxic and hypercapnic gas mixture resulting in rapid
      equilibration between alveolar gas and arterial blood. Use of a hyperoxic gas
      allows for the preferential examination of the central chemoreflexes (sensitive
      to CO(2)) with little if any effect of the peripheral (oxygen sensitive)
      chemoreflexes. After significant training, 15 healthy control subjects were
      assigned via a double blind procedure to receive an intravenous injection of
      placebo or CCK-4, using a between-subjects design. A between-subjects comparison
      was undertaken for the injection run (run #3) between subjects receiving the CCK
      4 injection and those receiving the placebo injection. As well, a within-subject
      comparison was undertaken to compare the results of the run following the
      injection (run #3) vs. the previous run when no injection took place (run #2). No
      significant differences were noted between subjects who received CCK-4 as
      compared with placebo for: basal or sub-threshold ventilation, threshold CO(2)
      resulting in a change in ventilation, or sensitivity of the central chemoreflex,
      regardless of whether a panic attack did or did not take place. In addition,
      within the group receiving the CCK-4 challenge, no significant differences were
      noted during run #3 (received the CCK-4 injection) and a prior run where no
      injection took place (run #2). We conclude that CCK-4 does not act to induce
      panic by altering the central (CO(2) sensitive) chemoreceptor.

PMID- 12007754
TI  - Dose conversion and titration with a novel, once-daily, OROS osmotic technology,
      extended-release hydromorphone formulation in the treatment of chronic malignant
      or nonmalignant pain.
AB  - The objective of this open-label, repeated-dose, single-treatment, multicenter
      study was to evaluate the outcomes associated with a standardized conversion from
      prior opioid therapy to a novel, once-daily, OROS osmotic technology, extended
      release (ER) hydromorphone formulation in an outpatient population with chronic
      malignant or nonmalignant pain. The study period was divided into 3 phases: the
      prior opioid stabilization phase (> or =3 days), the conversion and titration
      phase (3-21 days), and the maintenance phase (14 days). Patients were evaluated
      at 5 visits during the study period. Analgesic efficacy was measured using the
      Brief Pain Inventory (BPI). At baseline, patients were required to have daily
      oral morphine equivalent requirements of > or =45 mg. Prior oral or transdermal
      opioid therapy was converted to single daily doses of ER hydromorphone (8, 16,
      32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio.
      Immediate-release (IR) hydromorphone was given as rescue medication for
      breakthrough pain. Among the 445 patients who enrolled, 404 received the study
      medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had
      chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during
      which the total daily dose of ER hydromorphone remained unchanged and < or =3
      doses of IR hydromorphone per day were required) was attained by 73.8% of
      patients (298/404), of whom 70.1% (209/298) were stabilized with < or =2
      titration steps. The mean +/- standard deviation (SD) time to dose stabilization
      was 12.1 +/- 5.7 days (range of 3 to 33 days). The mean +/- SD final daily dose
      of ER hydromorphone was 63.4 +/- 129.2 mg. The mean +/- SD final daily dose of IR
      hydromorphone was 11.5 +/- 36.4 mg, and the mean +/- SD final number of daily
      doses of IR hydromorphone was 1.7 +/- 1.3. Intent-to-treat and completer analysis
      demonstrated significant improvements in BPI ratings from prior opioid therapy to
      the end of ER hydromorphone therapy (P < 0.01 for all pairwise comparisons).
      Adverse events were consistent with those expected of an opioid agonist in such a
      patient group, affecting primarily the gastrointestinal and central nervous
      systems. This uncontrolled study delineates a regimen by which patients with
      chronic malignant or nonmalignant pain can be readily converted from prior opioid
      therapy and titrated to an appropriate maintenance dose of ER hydromorphone.
      Controlled longitudinal studies are required to further evaluate the use of ER
      hydromorphone in patients with discrete chronic malignant or nonmalignant pain
      conditions.

PMID- 12007755
TI  - Putting cancer pain management regimens into practice at home.
AB  - The purpose of this study was to describe the difficulties with pain management
      that patients and family caregivers bring to a nurse's attention during a
      teaching and coaching intervention. Data were obtained from audiotaped and
      transcribed interactions between intervention nurses and patients (n = 52) and
      their family caregivers (n = 33) who were participating in a randomized clinical
      trial of a nursing intervention called the PRO-SELF Copyright Pain Control
      Program. Using qualitative content analysis, we found that patients had
      difficulty in seven areas when they attempted to put a pain management regimen
      into practice, namely: obtaining the prescribed medication(s), accessing
      information, tailoring prescribed regimens to meet individual needs, managing
      side effects, cognitively processing information, managing new or unusual pain,
      and managing multiple symptoms simultaneously. The findings from this study
      suggest that the provision of information about cancer pain management to
      patients and their family caregivers is not sufficient to improve pain control in
      the home care setting. Patients and their family caregivers require ongoing
      assistance with problem-solving to optimize their pain management regimen.

PMID- 12007756
TI  - Controlling cancer pain in primary care: the prescribing habits and knowledge
      base of general practitioners.
AB  - During recent years, the national policy of the United Kingdom has increasingly
      recognized the central place of general practitioners (GPs) in the care of cancer
      patients, from screening and early diagnosis through to palliative care and
      bereavement. There are, however, continuing reports of poor control of pain and
      other symptoms in the community. To investigate general practitioners'
      prescribing habits and knowledge of some key pain control issues in advanced
      cancer, a postal questionnaire surveyed a random sample of 450 East Anglian GPs.
      The response rate was 73.3%. Most respondents were familiar with the modern
      management of cancer pain, including the World Health Organization approach, the
      use of oral opioids, and the management of bone pain. There was less awareness of
      the drug options available for more uncommon situations, especially the dose
      conversion of oral morphine to subcutaneous diamorphine and drugs that may be
      used in syringe drivers. GPs in the UK are familiar with the management of the
      more common pain control problems. However, it is not appropriate to expect GPs
      to know the details of management of more unusual cancer pain problems.
      Specialist clinicians need to make themselves readily available to advise their
      generalist colleagues. The educational implications for GPs are discussed.

PMID- 12007757
TI  - Barriers to effective cancer pain management: a survey of hospitalized cancer
      patients in Australia.
AB  - The purpose of this study was to examine attitudinal barriers to effective pain
      management in a consecutively recruited cohort of 114 cancer patients from four
      Australian hospitals. When surveyed, 48% of this sample reported experiencing
      pain within the previous 24 hours. Of these, 56% reported this pain to be
      "distressing, horrible or excruciating," with large proportions indicating that
      this pain had affected their movement, sleep and emotional well-being. Three
      factors were identified as potentially impacting on patients' responses to pain
      poor levels of patient knowledge about pain, low perceived control over pain, and
      a deficit in communication about pain. A trend for older patients to experience
      more severe pain was also identified. These older patients reported being more
      willing to tolerate pain and perceive less control over their pain. Suggestions
      are made for developing patient education programs and further research using
      concepts drawn from broader social and behavioral models.

PMID- 12007758
TI  - Preliminary evaluation of a clinical syndrome approach to assessing cancer
      related fatigue.
AB  - The objectives of this study were to evaluate the reliability, validity, and
      utility of a newly developed clinical syndrome approach to assessing cancer
      related fatigue. Fifty-one patients who underwent blood or marrow transplantation
      an average of 6.9 months previously were administered a standardized interview
      designed to identify the presence of a clinical syndrome of cancer-related
      fatigue. Patients also completed self-report measures of fatigue, depression, and
      health-related quality of life. Comparisons among independent raters demonstrated
      high rates of reliability for the presence or absence of a cancer-related fatigue
      syndrome and its symptoms. Twenty-one percent of patients (n = 11) were found to
      meet criteria for diagnosis of a cancer-related fatigue syndrome. Compared to
      patients not meeting the diagnostic criteria, patients meeting the criteria
      reported fatigue that was greater (P < or = 0.05) in its severity, frequency,
      pervasiveness, and interference with quality of life. Patients who met criteria
      also demonstrated poorer role functioning, less vitality, and more depressive
      symptomatology (P < or = 0.05). These findings provide preliminary evidence of
      the reliability and validity of the methods used to assess the proposed clinical
      syndrome and suggest their utility in identifying patients experiencing
      clinically significant cancer-related fatigue.

PMID- 12007759
TI  - Impact of dyspnea, pain, and fatigue on daily life activities in ambulatory
      patients with advanced lung cancer.
AB  - This study aimed to compare the impact of dyspnea, pain, and fatigue on daily
      life activities in ambulatory patients with advanced lung cancer. One hundred
      seventy-one outpatients with advanced lung cancer completed a questionnaire about
      symptom severity and whether symptoms interfered with daily life activities
      (normal work, walking, sleep, mood, relation with other people, enjoyment of
      life, and general activities). The results indicated that 1) dyspnea and fatigue
      interfered with at least one daily life activity in more than half the patients,
      and pain in about 40%, 2) dyspnea and fatigue interfered predominantly with
      physical activities, such as walking and work, whereas pain interfered with all
      activities almost equally, and 3) symptoms rated as low severity (1 to 3 on a 0
      10-point numerical scale) were severe enough to interfere with at least one daily
      life activity. To recognize the impact of symptoms may contribute to provide
      better management.

PMID- 12007760
TI  - Assessing differences in care needs and service utilization in geriatric
      palliative care patients.
AB  - Little is known of the palliative care needs and experiences of older adults.
      This study explored whether these needs differed from those of younger patients.
      We performed a retrospective data analysis of 1184 palliative care consultations
      in a major teaching hospital. There were statistically significant differences
      across age groups in patient demographic and clinical characteristics, advance
      care planning, and service utilization. Patients over age 80 had a reduced
      prevalence of cancer, a higher prevalence of dementia and incapacity, more
      frequent decisions to withhold or withdraw life-sustaining treatments, and fewer
      interventions for symptom management. The palliative care needs of older adults
      appear to be substantially different from those of younger patients. Dementia and
      incapacity profoundly influence decision-making, requiring more time and
      communication with patients and families.

PMID- 12007761
TI  - The impact of chronic pain on life in the household.
AB  - To study what happens in a family where one member suffers from chronic pain, we
      quantitatively assessed the effect of chronic pain resulting from complex
      regional pain syndrome type 1 (CRPS) on 1) employment status, 2) time allocation,
      3) additional domestic help, and 4) out-of-pocket expenses of Dutch patients (n =
      50) and their spouses (n = 43). This study is the first to measure the effect of
      chronic pain on time allocation by means of a diary assessment technique. The
      results were compared with normative values for the Dutch population overall. In
      households containing a male patient, the total employment full time equivalent
      (FTE) decreased by 47% (P = 0.05), with the result that the mean household income
      decreased by $4,000 (P = 0.01). In those with a female patient, there was a
      reduction in FTE of 29% (P < 0.05), causing a decrease of the mean household
      income by $2,000 (p < 0.001). As compared with controls, patients were found to
      spend less time on paid employment, and to invest more time in household
      maintenance and housekeeping. Of 50 patients, 35 received a mean of 4.5 hours per
      week of domestic help. The mean out-of-pocket expenses related to CRPS amounted
      $1,350 per patient per year. Spouses were forced to invest more time on
      housekeeping and household maintenance, which resulted in less time for personal
      needs and leisure activities. There were only small differences in time
      allocation between cases where the sufferer was male or female and, similarly,
      only minor variation between hand-affected or foot-affected patients. Households
      with either male or hand-affected patients did prove to have higher out-of-pocket
      expenses as compared with households containing female or foot-affected patients.
      Those containing female or hand-affected patients required more domestic help
      than households either with male or foot-affected patients. The present study
      demonstrates that chronic pain due to CRPS has a profound impact on many aspects
      of the lives of both patients and their spouses.

PMID- 12007762
TI  - An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients
      with pain and other distressing symptoms.
AB  - We performed a pilot open-label, crossover trial of mirtazapine (15 and 30 mg at
      night) in advanced cancer patients with pain and other distressing symptoms.
      Twenty patients completed the trial and sixteen dropped out. Following a baseline
      assessment, patients completed a one-week observation period and were then
      randomized to a starting dose of either 15 mg or 30 mg of mirtazapine given at
      bedtime. After three weeks, subjects were switched to the alternate dose and
      followed by an additional three-week period, completing the treatment. The
      average age of the completers was 60.2 years and consisted of 7 women and 13 men.
      The majority were Caucasian (n = 18, 90%) and married (n = 18, 90%). The drop-out
      group did not significantly differ from the completers based on age, gender,
      race, marital status, or tumor type. We examined the impact of mirtazapine
      therapy on patients' levels of depression, pain intensity, appetite, insomnia,
      weight, and overall quality of life. A series of repeated measures ANOVAs were
      conducted to compare the completers' status at Weeks 1, 4, and 7 compared to
      baseline and to examine the interaction with starting dose and baseline
      observations. Scores on the Zung self-rating Depression Scale (F = 8.20, P <
      0.05) and the Functional Assessment of Cancer Therapy - General Measure (F =
      5.73, P < 0.05) were significantly improved at study end (Week 7) and were not
      dependent on mirtazapine dosage. Patients' weights were significantly higher at
      both Week 4 and Week 7, independent of dosage. Trend level differences were found
      on Memorial Pain Assessment Card items for pain, pain relief, and mood and on
      numeric rating scales measuring nausea, anxiety, insomnia, and appetite. This
      open-label pilot study suggests that mirtazapine may be effective for improving
      multiple symptoms, depression and quality of life in patients with advanced
      cancer. A controlled trial of this drug would be valuable.

PMID- 12007763
TI  - Simultaneous determination of the carboxylate and lactone forms of 10
      hydroxycamptothecin in human serum by restricted-access media high-performance
      liquid chromatography.
AB  - A simple restricted-access media (RAM) HPLC method for simultaneous determination
      of the lactone and carboxylate forms of 10-hydroxycamptothecin (HCPT) in human
      serum was established. Using a RAM Hisep analytical column, serum samples were
      directly injected into the HPLC system. The eluted peaks of two forms of HCPT
      were monitored with a fluorescence detector. The separation was completed in 17
      min. The linear range was 20-1000 ng/ml, intra-day and inter-day variations being
      less than 5%. The kinetic equation was introduced according to the analytical
      results. The equation shows that the course of the HCPT lactone form converting
      to carboxylate form in human serum at 4 degrees C is a first-order kinetic
      course. The concentration of each form at the moment of sampling was calculated
      by extrapolation.

PMID- 12007764
TI  - Simultaneous determination of clomipramine and its desmethyl and hydroxy
      metabolites in plasma of patients by high-performance liquid chromatography after
      solid-phase extraction.
AB  - Clomipramine (CMI) is a typical tricyclic antidepressant with a wide clinical
      spectrum, being used in major depressive, panic and obsessive-compulsive
      disorders. The relationship between clinical response and plasma levels of
      clomipramine and its N-desmethylated (N-desmethylclomipramine, DMCMI) and hydroxy
      metabolites remains unclear. In particular, limited information is available on
      the correlation with clinical response in patients with obsessive-compulsive
      disorder (OCD). This study describes a new sensitive method to simultaneously
      determine CMI and its major N-desmethylated and hydroxy-metabolites present in
      human plasma by HPLC with a UV detector. After a solid-phase extraction from
      plasma (Isolute C2 columns) the separation of the compounds was performed on a
      Lichrospher CN column (250 x 4 mm, 5 microm with a 2-cm pre-column) by an eluent
      consisting of 10 mM K(2)HPO(4)-acetonitrile-methanol (35:25:40 v/v/v) at a flow
      of 1.5 ml/min. UV detector was set at 214 nm. The lower limit of quantification
      for all the analytes was at least 5 ng/ml. The coefficients of variation ranged
      between 2.0 and 4.9% with recovery rates between 97.0 and 100.3%. Linear
      regression analyses showed correlation coefficients between 0.98 and 0.99. This
      method is simple, fast and reliable with good specificity and sensitivity. Solid
      phase extraction is efficient and rapid, allowing the extraction of several
      plasma samples on the same day and may therefore be usefully and realistically
      applied in the clinical context. We thus investigated the relevance of plasma
      levels of CMI and its metabolites as a predictor of clinical outcome in a group
      of 15 patients with OCD.

PMID- 12007765
TI  - Development and validation of a multi-analyte method for the detection of
      anabolic steroids in bovine urine with liquid chromatography-tandem mass
      spectrometry.
AB  - Detection of anabolic steroids in animal urine samples is currently performed
      with GC-MS in our lab. However we found that the detection of 17 alpha-trenbolone
      (17 alpha-TbOH), 4-chloroandrost-4-ene-3,17-dion (CLAD), 16- beta -OH-stanozolol
      (16OHstan) and alpha- and beta-boldenone (alpha -Bol, beta -Bol) was very
      difficult, if not impossible. Therefore a sensitive, specific and selective
      qualitative multi-analyte LC-MS-MS method was developed. The LC separation was
      achieved by using a Symmetry C(18) column and methanol-water-formic acid (54.7
      44.7-0.6) as a mobile phase at a flow-rate of 0.3 ml/min. The mass spectrometer
      was operated in multiple reaction monitoring mode with positive electrospray
      interface. Validation of the method was done according to draft SANCO/1805/2000
      Rev.1 and a CC beta smaller then 1 ng/ml was obtained for each compound.

PMID- 12007766
TI  - Quantification of rosuvastatin in human plasma by automated solid-phase
      extraction using tandem mass spectrometric detection.
AB  - An assay employing automated solid-phase extraction (SPE) followed by high
      performance liquid chromatography with positive ion TurboIonspray tandem mass
      spectrometry (LC-MS-MS) was developed and validated for the quantification of
      rosuvastatin (Crestor) in human plasma. Rosuvastatin is a hydroxy-methyl glutaryl
      coenzyme A reductase inhibitor currently under development by AstraZeneca. The
      standard curve range in human plasma was 0.1-30 ng/ml with a lower limit of
      quantification (LLOQ) verified at 0.1 ng/ml. Inaccuracy was less than 8% and
      imprecision less than +/-15% at all concentration levels. There was no
      interference from endogenous substances. The analyte was stable in human plasma
      following three freeze/thaw cycles and for up to 6 months following storage at
      both -20 and -70 degrees C. The assay was successfully applied to the analysis of
      rosuvastatin in human plasma samples derived from clinical trials, allowing the
      pharmacokinetics of the compound to be determined.

PMID- 12007767
TI  - Liquid chromatography--mass spectrometric method combined with derivatization for
      determination of 1 alpha-hydroxyvitamin D(3) in human plasma.
AB  - A stable isotope dilution liquid chromatography-tandem mass spectrometric (LC-MS
      MS) method for the determination of plasma 1 alpha-hydroxyvitamin D(3) [1
      alpha(OH)D(3)] has been developed. The method employed derivatization, the
      reaction with 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyl]
      1,2,4-triazoline-3,5-dione and acetylation, which significantly improved the
      ionization efficiency of 1 alpha(OH)D(3) with a detection limit of 6.3 fmol per
      injection. The plasma 1 alpha(OH)D(3) was extracted with acetonitrile, purified
      with disposable cartridges, derivatized and subjected to LC-MS-MS analysis using
      atmospheric pressure chemical ionization. The intra- and inter-assay coefficients
      of variation were below 10.6 and 4.7%, respectively, and the analytical recovery
      of 1 alpha(OH)D(3) was quantitative. The limit of quantitation was 25 pg/ml for a
      1.0-ml plasma aliquot. The application of the developed method to the sample of a
      volunteer orally given 1 alpha(OH)D(3) was also described.

PMID- 12007768
TI  - Improved and validated method for the determination of Delta(9)
      tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in serum, and
      in human liver microsomal preparations using gas chromatography-mass
      spectrometry.
AB  - A validated method for the quantification of Delta(9)-tetrahydrocannabinol (THC)
      and its main metabolites 11-hydroxy-tetrahydrocannabinol (OH-THC) and 11-nor-9
      carboxy-tetrahydrocannabinol (THC-COOH) in serum is presented. The substances
      were isolated by solid-phase extraction, derivatised by methylation, and analysed
      by means of GC-MS in the selected ion monitoring mode. Quantitation was achieved
      by the addition of deuterated analogues as internal standards. The method was
      linear up to 10 ng/ml for THC and OH-THC, and up to 50 ng/ml for THC-COOH. The
      limits of quantification were 0.62 ng/ml for THC, 0.68 ng/ml for OH-THC and 3.35
      ng/ml for THC-COOH. The limits of detection for the least intensive ions were
      0.52 ng/ml for THC, 0.49 ng/ml for OH-THC and 0.65 ng/ml for THC-COOH. The method
      was validated according to the requirements of the Journal of Chromatography B.
      The method has been routinely used on samples from drivers suspected of "driving
      under the influence". In addition to the forensic application, a cross-validation
      was carried out by applying the method developed for serum to human liver
      microsomal preparation samples.

PMID- 12007769
TI  - Gas chromatographic-mass spectrometric analysis of residual solvent trapped into
      illicit cocaine exhibits using head-space solid-phase microextraction.
AB  - The analysis of solvent residues trapped into crystals of illicit drugs provides
      useful evidence for monitoring current use trend in the chemical underground, and
      is also a suitable tool to achieve the complete chemical characterisation of
      street drugs for comparative examination of separate specimens. This paper
      describes a method developed in order to perform simultaneous qualitative and
      quantitative analysis of solvent residues in cocaine samples. The method is based
      on GC-MS analysis of solvents after their extraction/concentration from drug
      matrices accomplished by solid-phase microextraction (SPME) in static head space.
      The proposed method has been used to detect residues of solvents in 47 illicit
      street cocaine samples. Quantitative analyses were carried out only for the
      solvents identified at concentration values higher than 1 ppm. Statistical
      evaluation of our results allowed us to group the illicit samples into various
      classes according to different kinds of residual solvent, in connection with
      different clandestine manufacturing processes used to prepare illicit cocaine.

PMID- 12007770
TI  - New liquid chromatographic assay with electrochemical detection for the
      measurement of amifostine and WR1065.
AB  - A high-performance liquid chromatographic method (HPLC) was developed for the
      analysis of the radio- and chemo-protectant, amifostine and its active metabolite
      WR1065 in deproteinized human whole blood and plasma. The two compounds were
      quantified by measuring WR1065 after two different sample pretreatment
      procedures. During these procedures, amifostine was quantitatively converted into
      WR1065, by incubating the sample at 37 degrees C for 4 h at pH<1.0. The resulting
      amounts of WR1065 were determined by HPLC with coulometric detection (analytical
      cell: E(1)=200 mV and E(2)=600 mV; guard cell: E(G)=650 mV). The WR1065 standard
      curve ranged from 0.37 to 50.37 microM. The lower limit of quantitation of WR1065
      was 0.25 microM. The within- and between-day precisions were < or = 4.3% and < or
      = 6.0% for amifostine, < or = 4.4% and < or = 3.8% for WR1065, respectively. The
      within- and between-day accuracy ranged from 95.4 to 97.7% and 95.4 to 97.8% for
      amifostine, and from 97.1 to 101.7% and 97.2 to 99.7% for WR1065, respectively.
      This method minimizes WR1065 loss during sample preparation, and allows for rapid
      analysis of both compounds on one system. Furthermore, the application of a
      coulometric electrode is more efficient and requires less maintenance than
      previously published methods for the two compounds.

PMID- 12007771
TI  - Highly sensitive chromatographic assay for dopamine determination during in vivo
      cerebral microdialysis in the rat.
AB  - A highly sensitive, yet simple, isocratic high-performance liquid chromatographic
      (HPLC) assay with electrochemical detection (ED) for the determination of
      extracellular dopamine (DA) in brain microdialysates is presented. The method
      makes possible the detection of less than 100 pM (less than 1 fmol on column) and
      the quantitation of 200 pM (2 fmol on column) of DA with the use of a narrow-bore
      rather than capillary or microbore column. Analysis is feasible within an 11-min
      run-time, and thus is suitable for the relatively short sampling intervals used
      in microdialysis experiments. In the calibration range of 0.2 to 10 nM, the
      method has excellent linearity and precision, with intra-day relative standard
      deviations (RSD) of 0.5-2.4% and between-day RSD of 2.1-4.3%.

PMID- 12007772
TI  - Simultaneous determination of intact cisplatin and its metabolite monohydrated
      cisplatin in human plasma.
AB  - Cisplatin is a cytotoxic platinum compound, used in the treatment of several
      solid tumors. Cisplatin and to a greater extent its hydrolysis product
      monohydrated cisplatin are responsible for side-effects like nephrotoxicity. A
      sensitive, accurate and precise method was developed to simultaneously determine
      cisplatin and monohydrated cisplatin in plasma. The compounds were separated by
      high-performance liquid chromatography and quantified by off-line furnace atomic
      absorption spectrophotometry. The linear ranges for cisplatin and monohydrated
      cisplatin in deproteinized plasma were 60-600 and 87.5-700 nM, respectively. From
      plasma, the mean recovery of cisplatin was 83.2% and that of monohydrated
      cisplatin 79.1%. The lower limits of quantification of cisplatin and monohydrated
      cisplatin in deproteinized plasma were 60 and 87.5 nM, respectively. Over the
      whole calibration range, the within- and between-day accuracy of intact cisplatin
      ranged from 100.7 to 111.4 and 94.8-102.0%, respectively. The within- and between
      day accuracy of monohydrated cisplatin ranged from 107.1 to 113.3 and 101.4
      104.9%, respectively. The within-day and between-day precision of cisplatin
      ranged from 3.4 to 11.5 and 7.3-10.3%, respectively. For monohydrated cisplatin,
      the within-day and between-day precision ranged from 3.7 to 6.2 and 5.6-7.9%,
      respectively. Currently, the developed assay has been implemented in
      pharmacokinetic studies of patients treated with cisplatin alone or in
      combination with other drugs.

PMID- 12007773
TI  - Quantification and stability of everolimus (SDZ RAD) in human blood by high
      performance liquid chromatography-electrospray tandem mass spectrometry.
AB  - We report here a validated method for the quantification of a new
      immunosuppressant drug, everolimus (SDZ RAD), using HPLC-tandem mass
      spectrometry. Whole blood samples (500 microl) were prepared by protein
      precipitation, followed by C(18) solid-phase extraction. Mass spectrometric
      detection was by selected reaction monitoring with an electrospray interface
      operating in positive ionization mode. The assay was linear from 0.5 to 100
      microg/l (r(2) > 0.996, n = 9). The analytical recovery and inter-day
      imprecision, determined using whole blood quality control samples (n = 5) at 0.5,
      1.2, 20.0, and 75.0 microg/l, was 100.3 - 105.4% and < or = 7.6%, respectively.
      The assay had a mean relative recovery of 94.8 +/- 3.8%. Extracted samples were
      stable for up to 24 h. Fortified everolimus blood samples were stable at -80
      degrees C for at least 8 months and everolimus was found to be stable in blood
      when taken through at least three freeze-thaw cycles. The reported method
      provides accurate, precise and specific measurement of everolimus in blood over a
      wide analytical range and is currently supporting phase II and III clinical
      trials.

PMID- 12007774
TI  - Development and validation of a plasma assay for acyclovir using high-performance
      capillary electrophoresis with sample stacking.
AB  - A sensitive plasma assay for acyclovir has been developed and validated.
      Acyclovir was separated from plasma components using Oasis HLB columns.
      Separation was obtained with no plasma interference using micellar electrokinetic
      chromatography (175 mM SDS) and hydroxypropyl-beta-cyclodextrin (100 mM) in 90 mM
      borate buffer (pH 8.8) containing 0.2% NaCl. High sensitivity was achieved by
      large volume sample introduction and stacking. The linear range was from 20 to
      10000 ng/ml with a limit of quantitation of 20 ng/ml. This method is a viable
      alternative to HPLC because of its high separation and sensitivity,
      reproducibility, and adaptability to other nucleoside analogs.

PMID- 12007775
TI  - Determination of cannabinoids by gas chromatography-mass spectrometry and large
      volume programmed-temperature vaporiser injection using 25 microl of biological
      fluid.
AB  - This paper presents a GC-MS confirmation method, based on large-volume programmed
      temperature vaporisation (PTV) injection, for the determination of cannabinoids
      in plasma samples (or whole blood) with deuterium-labelled internal standards
      using only 25 microl of biological fluid. The analytes, Delta(9)
      tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC)
      and 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THC-COOH), were enriched by
      means of solid-phase extraction cartridges containing octadecyl-bonded silica and
      were, subsequently, methylated. A 20 microl aliquot of an extract in hexane was
      injected into a PTV in solvent split mode. Method development and the results of
      the analyses of standard reference material and real samples are presented and
      discussed. This micro-method is precise and sensitive enough to assess relevant
      cannabinoid levels in human blood for forensic investigations as well as for
      clinical applications.

PMID- 12007776
TI  - A sensitive gas chromatographic/mass spectrometric method for the resolution and
      quantification of ethosuximide enantiomers in biological fluids.
AB  - A modified specific, sensitive and reproducible chiral gas chromatographic (GC)
      method for the resolution and quantification of ethosuximide enantiomers in urine
      and plasma was developed. The samples were extracted by liquid-liquid extraction,
      using diethylether and the enantiomers were separated and quantified on a chiral
      gas chromatographic column (25QC2 / CYDEX- beta 0.25). The method involved the
      use of GC/MS instrumentation for the acquisition of data in the electron impact
      selective-ion monitoring mode, collecting ions characteristic of both
      ethosuximide and alpha, alpha - dimethyl - beta - methylsuccinimide, the internal
      standard and of mass-to-charge ratio (m/z) exactly equal to 55 and 70 units. The
      limit of quantitation of the method was 2.5 microg/ml for both urine and plasma
      with both enantiomers. The method proved to be linear, precise and reproducible
      in the 5-300 microg/ml concentration range for urine samples and in the 10-250
      microg/ml concentration range for plasma samples. Future research work envisaged
      the application of this method in pharmacokinetic and pharmacodynamic studies.

PMID- 12007777
TI  - Validation of a liquid chromatographic-tandem mass spectrometric method for the
      measurement of (R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2-pyridyl)-1H-1,4
      benzodiazepin-3-yl]-3-(3-methylaminophenyl)urea (YF476) in human plasma.
AB  - A sensitive and specific liquid chromatographic-tandem mass spectrometric (LC-MS
      MS) method has been validated for the measurement of YF476 in human plasma. The
      method involves a simple liquid-liquid extraction procedure, chromatography of
      the extracts on a C(18) column, atmospheric pressure chemical ionisation and
      detection in the multiple reaction monitoring mode. The calibration line was
      linear over the concentration range 0.1 ng/ml (the limit of quantification) to
      25.0 ng/ml. Intra- and inter-batch precision was <14% and intra- and inter-batch
      accuracy was <11% over the entire calibration range. The bioanalytical method is
      robust and has been used for the analysis of many samples from human subjects
      involved in early clinical studies (Phase I).

PMID- 12007778
TI  - Determination of acyclovir in maternal plasma, amniotic fluid, fetal and
      placental tissues by high-performance liquid chromatography.
AB  - Acyclovir [9-[(2-hydroxyethoxy)-methyl]-guanosine, Zovirax, ACV] is a synthetic
      purine nucleoside analog active against herpes simplex virus types 1 (HSV-1), 2
      (HSV-2), and varicella zoster virus. Acyclovir has frequently been used in HSV-2
      seropositive mothers to prevent prenatal transmission of herpes virus to their
      unborn children. A fast and reproducible HPLC method for the determination of the
      highly polar acyclvoir in maternal rat plasma, amniotic fluid, placental tissue,
      and fetal tissue has been developed and validated. Plasma and amniotic fluid
      samples were prepared by protein precipitation using 2 M perchloric acid and
      syringe filtering. Tissue samples were homogenized in distilled water,
      centrifuged, and extracted using a C(18) solid-phase extraction method prior to
      analysis. Baseline resolution was achieved for acyclovir and the internal
      standard gancyclovir, an anti-viral of similar structure to acyclovir, using an
      Agilent Eclipse XDB C(8) column (150 x 2.1 mm, 5 microm). The mobile phase used
      for the plasma and amniotic fluid was 10 mM acetate/citrate buffer-3.7 mM aqueous
      octanesulfonic acid (87.5:12.5, v/v) at a flow-rate of 0.2 ml/min. The mobile
      phase used for the tissue samples was 30 mM acetate/citrate buffer with 5 mM
      octanesulfonic acid-acetonitrile (99:1, v/v). Both aqueous mobile phase portions
      were pH adjusted to 3.08. All separations were done using an Agilent 1100 Series
      HPLC system with UV detection of 254 nm. The assay was validated for each matrix
      over a range of 0.25-100 microg/ml over 3 days using five replicates of three
      spiked concentrations. The relative standard deviation and percent error for each
      validation data set was <15% for middle and high quality control (QC) points and
      <20% for all low QC points. All calibration curves showed good linearity with an
      R(2)>0.99. The extraction efficiency for recovery of acyclovir from all matrices
      was >80%.

PMID- 12007779
TI  - Measurement of S-nitrosoalbumin by gas chromatography--mass spectrometry. III.
      Quantitative determination in human plasma after specific conversion of the S
      nitroso group to nitrite by cysteine and Cu(2+) via intermediate formation of S
      nitrosocysteine and nitric oxide.
AB  - Highly contradictory data exist on the normal plasma basal levels in humans of S
      nitrosoproteins, in particular of S-nitrosoalbumin (SNALB), the most abundant
      nitric oxide (.NO) transport form in the human circulation with a range of three
      orders of magnitude (i.e., 10 nM-10 microM). In previous work we reported on a GC
      MS method for the quantitative determination of SNALB in human plasma. This
      method is based on selective extraction of SNALB and its 15N-labeled SNALB analog
      (S(15)NALB) used as internal standard on HiTrapBlue Sepharose affinity columns,
      HgCl(2)-catalysed conversion of the S-nitroso groups to nitrite and [15N]nitrite,
      respectively, their derivatization to the pentafluorobenzyl derivatives and
      quantification by GC-MS. By this method we had measured SNALB basal plasma levels
      of 181 nM in healthy humans. It is generally accepted that HgCl(2)-catalysed
      conversion of S-nitroso groups into nitrite is specific. In consideration of the
      highly divergent SNALB plasma levels in humans reported so far, we were
      interested in an additional method that would allow specific conversion of S
      nitroso groups into nitrite. We found that treatment with cysteine plus CuSO(4)
      is as effective and specific as treatment with HgCl(2). The principle of the
      cysteine/CuSO(4) procedure is based on the transfer of the S-nitroso group from
      SNALB to cysteine yielding S-nitrosocysteine, and its subsequent highly Cu(2+)
      sensitive conversion into nitrite via intermediate.NO formation. Similar SNALB
      concentrations in the plasma of 10 healthy humans were measured by GC-MS using
      HgCl(2) (156+/-64 nM) and cysteine/CuSO(4) (205+/-96 nM). Our results strongly
      suggest that SNALB is an endogenous constituent in human plasma and that its
      concentration is of the order of 150-200 nM under physiological conditions.

PMID- 12007780
TI  - High-throughput bioanalytical method using automated sample preparation and
      liquid chromatography-atmospheric pressure ionspray mass spectrometry for
      quantitative determination of glybenclamide in human serum.
AB  - A liquid chromatographic-mass spectrometric (LC-MS) method with rapid automated
      sample preparation was developed and validated for determination of glybenclamide
      in human serum. Glybenclamide and its deuterated labelled internal standard were
      extracted from human serum samples by automated solid-phase extraction. The
      extract was injected into the LC-MS system for analysis. Glybenclamide and its
      internal standard were measured in multiple ion monitoring mode. The method was
      validated over a range of 10-1000 ng/ml with good accuracy and precision and was
      applicable for pharmacokinetic studies.

PMID- 12007781
TI  - Preparation of immuno-affinity membranes for cholesterol removal from human
      plasma.
AB  - Anti-low density lipoprotein antibody (anti-LDL) immobilized
      polyhydroxyethylmethacrylate (pHEMA) based membrane was prepared for selective
      removal of cholesterol from hypercholesterolemic human plasma. In order to
      further increase blood-compatibility, a newly synthesized comonomer,
      methacryloylamidophenylalanine (MAPA) was included in the membrane formulation.
      p(HEMA-MAPA) membranes were produced by a photopolymerization and then
      characterized by swelling tests, SEM and contact angle studies. Blood
      compatibility tests were also investigated. The water swelling ratio of the
      p(HEMA-MAPA) membrane increases significantly (133.2.9%) compared with pHEMA
      (58%). p(HEMA-MAPA) membranes have large pores around in the range of 5-10
      microm. All the clotting times increased when compared with pHEMA membranes. Loss
      of platelets and leukocytes was very low. The maximum anti-LDL antibody
      immobilization was achieved around pH 7.0. Immobilization of anti-LDL antibody
      was 12.6 mg/ml. There was a very low non-specific cholesterol adsorption onto the
      plain p(HEMA-MAPA) membranes, about 0.36 mg/ml. Anti-LDL antibody immobilized
      membranes adsorbed in the range of 4.5-7.2 mg cholesterol/ml from
      hypercholesterolemic human plasma. Up to 95% of the adsorbed LDL antibody was
      desorbed. The adsorption-desorption cycle was repeated 10 times using the same
      membrane. There was no significant loss in the adsorption capacity.

PMID- 12007782
TI  - Isolation and identification of the glucuronide of 4-(3H-1,2-dihydro-1
      pyrrolizinone-2-methylamino)benzoic acid from rabbit urine.
AB  - The metabolic profile of 3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1
      pyrrolizinone (SFZ-47), a putative non-steroidal anti-inflammatory pro-drug, has
      been studied in rabbit urine. Semi-preparative reversed-phase HPLC of 24 h urine
      from two rabbits given single oral doses of SFZ-47 (200 mg) allowed the
      separation of SFZ-47 together with the oxidative metabolite 4-(3H-1,2-dihydro-1
      pyrrolizinone-2-methylamino)benzoic acid (SFZ-47-COOH) and its glucuronide
      conjugate. The glucuronide was characterized by ESI-MS(n) and (1)H NMR and shown
      to be the 1-O-acyl beta-D-glucuronide conjugate of SFZ-47-COOH. The method gave
      excellent resolution of the glucuronide from endogenous constituents in urine and
      may be suitable for the preparation of glucuronide metabolites of other drugs.

PMID- 12007783
TI  - Simplified high-performance liquid chromatographic method for determination of
      risperidone and 9-hydroxyrisperidone in plasma after overdose.
AB  - For toxicological purposes, a HPLC assay was developed for the simultaneous
      determination of risperidone and 9-hydroxyrisperidone in human plasma. After a
      single-step liquid-liquid extraction, both compounds were separated on a C(18)
      column and measured at 280 nm. A good inter-assay accuracy (<116%) was achieved
      with inter-assay precision less than 12%. Quantification limits were 10 ng/ml.
      This rapid method (run time <5 min) is currently used for poison management.

PMID- 12007784
TI  - Insulin induces PFKFB3 gene expression in HT29 human colon adenocarcinoma cells.
AB  - Fructose 2,6-bisphosphate is present at high concentrations in many established
      lines of transformed cells. It plays a key role in the maintenance of a high
      glycolytic rate by coupling hormonal and growth factor signals with metabolic
      demand. The concentration of fructose 2,6-bisphosphate is controlled by the
      activity of the homodimeric bifunctional enzyme 6-phosphofructo-2-kinase/fructose
      2,6-bisphosphatase (PFK-2). We report here the PFKFB-3 gene expression control by
      insulin in the human colon adenocarcinoma HT29 cell line. The incubation of these
      cells with 1 microM insulin resulted in an increase in the PFK-2 mRNA level after
      6 h of treatment, this effect being blocked by actinomycin D. Furthermore,
      insulin induced ubiquitous PFK-2 protein levels, that were evident after a lag of
      3 h and could be inhibited by incubation with cycloheximide.

PMID- 12007785
TI  - Calyculin A-induced endothelial cell shape changes are independent of [Ca(2+)](i)
      elevation and may involve actin polymerization.
AB  - Changes in endothelial cell (EC) shape result in inter-EC gap formation and
      subsequently regulate transendothelial passage. In this work, we investigated the
      effects of protein phosphorylation (induced by inhibition of protein
      phosphatases) on EC shape changes. Treatment of bovine pulmonary artery
      endothelial cells (BPAEC) with calyculin A (100 nM, an inhibitor of protein
      Ser/Thr phosphatases 1 and 2A) resulted in cell retraction, surface bleb
      formation and cell rounding. Trypan blue and electrophysiological experiments
      suggested that the plasma membrane of these rounded cells maintained functional
      integrity. Calyculin A-induced morphological changes were strongly inhibited by
      staurosporine, but not affected by specific inhibitors of the myosin light chain
      (MLC) kinase, protein kinases A, C and G, and tyrosine kinases. The calyculin A
      effects were not mimicked by phorbol myristate acetate, dibutyryl cAMP, 8-bromo
      cGMP or ionomycin. Cytochalasin B (an inhibitor of actin polymerization) almost
      completely abolished such shape changes while colchicine (an inhibitor of
      microtubule polymerization) had no inhibitory effect at all. Ca(2+) imaging
      experiments showed that the morphological changes were not associated with any
      global or local cytosolic Ca(2+) concentration ([Ca(2+)](i)) elevation. The
      results suggest that calyculin A unmasked the basal activities of some protein
      Ser/Thr kinases other than MLC kinase and protein kinases A, C and G; these
      unknown kinases might cause BPAEC shape changes by a mechanism involving actin
      polymerization but not [Ca(2+)](i) elevation.

PMID- 12007786
TI  - Assessment of the microbody luminal pH in the filamentous fungus Penicillium
      chrysogenum.
AB  - The enzymes of the penicillin biosynthetic pathway in Penicillium chrysogenum are
      located in different subcellular compartments. Consequently, penicillin pathway
      precursors and the biologically active penicillins have to cross one or more
      membranes. The final enzymatic step that is mediated by acyltransferase takes
      place in a microbody. The pH of the microbody lumen in penicillin producing cells
      has been determined with fluorescent probes and mutants of the green fluorescent
      protein and found to be slightly alkaline.

PMID- 12007787
TI  - WTH3, a new member of the Rab6 gene family, and multidrug resistance.
AB  - The WTH3 gene was obtained by a DNA fragment isolated by the methylation
      sensitive representational difference analysis technique due to its
      hypermethylation in the human multidrug resistant (MDR) breast cancer cell line
      MCF7/AdrR. The WTH3 gene product is 89% and 91% identical to the human Rab6 and
      Rab6c proteins, but possesses an elongated C-terminal region which contains 46
      extra amino acids. Nevertheless, we consider the WTH3 gene a new member of the
      Rab6 gene family. Semi-quantitative reverse transcriptase-polymerase chain
      reaction results showed that WTH3 was 15 and 4 times downregulated in MCF7/AdrR
      and MES-SA/Dx5, a human MDR uterine sarcoma cell line, as compared to their non
      MDR parental cell lines. Permanent expression of the WTH3 transgene in MDR cell
      lines increased to varying degrees their sensitivity to several anticancer drugs,
      which included doxorubicin, taxol, vinblastine, vincristine, and etoposide, as
      compared to the control sublines transfected with the empty vector. Flow
      cytometry and fluorescence microscope experiments suggest that the WTH3 transgene
      stimulated the host's uptake and retention of DOX. Our results imply that the
      WTH3 gene plays a role(s) in MDR phenotype development in vitro.

PMID- 12007788
TI  - Retrograde transport of protein toxins under conditions of COPI dysfunction.
AB  - Retrograde transport dependent on coat protein I (COPI) was impaired using two
      different approaches and the effects on the retrograde transport of protein
      toxins were investigated. One approach was to study ldlF cells that express a
      temperature-sensitive defect in the epsilon-COP subunit of COPI. The second
      approach was to treat cells with 1,3-cyclohexanebis(methylamine) (CBM), a drug
      that interferes with the binding of COPI to Golgi membranes. With both
      approaches, cells remained sensitive to a variety of protein toxins regardless of
      whether the toxins contained a KDEL motif. Moreover, cholera toxin, which
      contains a KDEL sequence, was observed by immunofluorescence microscopy to enter
      the endoplasmic reticulum of Vero cells in the presence of CBM. These data
      support published evidence indicating the presence in cells of a COPI- and KDEL
      receptor-independent pathway of retrograde transport from the Golgi complex to
      the endoplasmic reticulum. In addition, the results suggest that certain toxins
      containing a KDEL motif may use either the COPI-dependent or COPI-independent
      pathway of retrograde transport.

PMID- 12007789
TI  - The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck
      localization to lipid rafts and T cell signaling.
AB  - Palmitoylation of cysteines 3 and 5 is necessary for targeting Lck to lipid rafts
      and is needed for Lck function in T cell receptor (TCR) signaling. Point
      mutations of cysteines 3 and 5 result in a form of Lck that fails to associate
      with the plasma membrane, which limits the usefulness of this genetic approach to
      address the role of palmitoylation in the distribution of Lck within the plasma
      membrane. To circumvent this problem, we sought to identify a palmitic acid
      analogue that would enable plasma membrane association of Lck, but not facilitate
      its localization within lipid rafts. Here we examined the effects of the
      heteroatom-substituted analogue of palmitic acid, 13-oxypalmitic acid (13-OP), on
      Lck subcellular localization and function. 13-OP is similar in chain length to
      palmitic acid, but possesses reduced hydrophobicity. We found that treatment of
      cells with 13-OP inhibited incorporation of omega-[(125)I]iodopalmitate into Lck.
      13-OP inhibited localization of Lck to lipid rafts without altering its membrane
      localization. Consistent with the dissociation of Lck from rafts, treatment with
      13-OP abolished Lck association with the GPI-anchored protein, CD48, but not the
      transmembrane glycoprotein CD4. Jurkat T cells treated with 13-OP showed marked
      reduction in tyrosine phosphorylation and activation of mitogen-activated protein
      kinase upon TCR stimulation. In conclusion, the less hydrophobic analogue of
      palmitate, 13-OP, alters the normal acylation of Lck that provides Lck with the
      necessary hydrophobicity and tight packing order required for inclusion in lipid
      rafts.

PMID- 12007790
TI  - Diverse effects of RacV12 on cell transformation by Raf: partial inhibition of
      morphological transformation versus deregulation of cell cycle control.
AB  - Activated Raf kinases and Rac GTPases were shown to cooperate in the oncogenic
      transformation of fibroblasts, which is characterised by the disassembly of the
      cellular actin cytoskeleton, a nearly complete loss of focal adhesion complexes
      and deregulated cell proliferation. This is surprising since the Rac GTPase
      induces actin structures and the adhesion of suspended cells to extracellular
      matrix proteins. NIH 3T3 cells expressing a hydroxytamoxifen-inducible oncogenic
      c-Raf-1-oestrogen receptor fusion protein (c-Raf-1-BxB-ER, N-BxB-ER cells)
      undergo morphological transformation upon stimulation of the Raf kinase. We show
      that treatment with the Rac, Rho and Cdc42 activating Escherichia coli toxin CNF1
      or coexpression of an activated RacV12 mutant partially inhibits and reverses the
      disassembly of cellular actin structures and focal adhesion complexes by
      oncogenic Raf. Activation of the Rac GTPase restores actin structures and focal
      adhesion complexes at the cellular boundary, leading to spreading of the
      otherwise spindle-shaped Raf-transformed cells. Actin stress fibres, however,
      which are regulated by the function of the Rho GTPase, are disassembled by
      oncogenic Raf even in the presence of activated Rac and Rho. With respect to the
      RacV12-mediated spreading of Raf-transformed cells, we postulate an anti
      oncogenic function of the activated Rac. Another feature of cell transformation
      is the deregulation of cell cycle control. NIH 3T3 cells expressing high levels
      of the c-Raf-1-BxB-ER protein undergo a cell cycle arrest upon stimulation of the
      oncogenic Raf kinase. Our results show that in N-BxB-ER-RacV12 cells the
      expression of the activated RacV12 mediates cell proliferation in the presence of
      high-intensity Raf signals and high levels of the Cdk inhibitor p21(Cip1). These
      results indicate a pro-oncogenic function of the Rac GTPase with respect to the
      deregulation of cell cycle control.

PMID- 12007791
TI  - Transcriptome changes during intestinal cell differentiation.
AB  - The expression of 18149 genes have been analysed during the differentiation of
      the human intestinal cell line Caco-2. cDNA probes from undifferentiated and
      differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an
      array on a nylon membrane. A remarkable change in the transcriptome was observed
      during the differentiation of the Caco-2 cells. 8762 of the 18149 genes analysed
      were expressed above background level in the undifferentiated Caco-2 cells,
      whereas only 5767 genes were expressed above background in differentiated Caco-2
      cells. This pattern of expression was caused by a general down-regulation of
      genes in the low abundance class. Similar results were found using mouse small
      intestinal crypt and villus cells, suggesting that the phenomenon also occurs in
      the intestine in vivo. The expression data were subsequently used in a search for
      markers for subsets of epithelial cells by performing reverse transcriptase
      polymerase chain reaction on RNA extracted from laser dissected intestinal crypt
      and villi. In a screen of eight transcripts one - SART3 - was identified as a
      marker for human colonic crypts.

PMID- 12007792
TI  - Gastric irritant-induced apoptosis in guinea pig gastric mucosal cells in primary
      culture.
AB  - When the gastric mucosa is exposed to various irritants, apoptosis and subsequent
      gastric mucosal lesion can result in vivo. We here show that gastric irritants
      induced apoptosis in gastric mucosal cells in primary culture and examined its
      molecular mechanism. Ethanol, hydrogen peroxide, and hydrochloric acid all
      induced, in a dose-dependent manner, cell death, apoptotic DNA fragmentation, and
      chromatin condensation, suggesting that each of these gastric irritants induced
      apoptosis in vitro. Since each of these irritants decreased the mitochondrial
      membrane potential and stimulated the release of cytochrome c from mitochondria,
      gastric irritant-induced apoptosis seems to be mediated by mitochondrial
      dysfunction. Caspase-3, caspase-8, and caspase-9-like activities were all
      activated simultaneously by each of these irritants and the activation was
      concomitantly with cell death and apoptotic DNA fragmentation. Furthermore, pre
      treatment of gastric mucosal cells with an inhibitor of caspase-8 suppressed the
      onset of cell death as well as the stimulation of caspase-3- and caspase-9-like
      activities caused by each of these gastric irritants. Based on these results, we
      consider that caspase-8, an initiator caspase, plays an important role in gastric
      irritant-induced apoptosis.

PMID- 12007793
TI  - Characterization and location of Src-dependent tyrosine phosphorylation in rat
      brain mitochondria.
AB  - Analysis of protein phosphorylation in highly purified rat brain mitochondria
      revealed the presence of several alkali-stable phosphoproteins whose
      phosphorylation markedly increases upon treatment with peroxovanadate and Mn(2+),
      a property indicating tyrosine phosphorylation. These include three prominent
      bands, with apparent sizes of 50, 60, and 75 kDa, which are detectable by anti
      phosphotyrosine. Tyrosine phosphorylation disappears when mitochondria are
      treated with PP2, an inhibitor of the Src kinase family, suggesting the presence
      of members of this family in rat brain mitochondria. Immunoblotting and
      immunoprecipitation assays of mitochondrial lysates confirmed the presence of
      Fyn, Src and Lyn kinases, as well as Csk, a protein kinase which negatively
      controls the activity of the Src kinase family. Results show that tyrosine
      phosphorylated proteins are membrane-bound and that they are located on the inner
      surface of the outer membrane and/or the external surface of the inner membrane.
      Instead, Src tyrosine kinases are mainly located in the intermembrane space - in
      particular, as revealed by immunogold experiments for Lyn kinase, in the cristal
      lumen. Rat brain mitochondria were also found to possess a marked level of
      tyrosine phosphatase activity, strongly inhibited by peroxovanadate.

PMID- 12007794
TI  - Biochemical analysis of a T cell receptor alpha-like molecule involved in antigen
      nonspecific suppression.
AB  - Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine
      T cell hybridoma, possesses a pleiotropic antigen-nonspecific suppressive
      function. We have shown that 70 kDa MNSF comprises an 8 kDa ubiquitin-like
      polypeptide (Ubi-L) and 62 kDa T cell receptor (TCR) alpha-like molecule. Ubi-L
      binds specifically to its 82 kDa receptor protein on target cells. In the current
      study, we have further characterized the biochemical nature of the TCR(alpha)
      like molecule. The 62 kDa protein was separated into two species of 46 kDa and 16
      kDa on reverse-phase HPLC. Anti-TCR(alpha) monoclonal antibody recognized the 46
      kDa, but not the 16 kDa protein. Anti-TCRbeta monoclonal antibody failed to
      recognize these proteins. Ubi-L conjugated to the 46 kDa protein, whereas Ubi-L
      lacking its C-terminal Gly-Gly did not. Although Ubi-L was labile both to heating
      at 56 degrees C and to acidification to pH 4, the Ubi-L-46 kDa protein complex
      was unaffected by these treatments. In addition, the 46 kDa protein elongated the
      Ubi-L-induced protein tyrosine phosphorylation in a concanavalin A-activated
      murine T helper type 2 clone, D10 cells. One of the four tryptic peptide
      sequences derived from the 46 kDa protein was in alignment with a related
      sequence found in the J(alpha) region of the TCR(alpha), including the highly
      conserved motif F-G-X-G-T-X-L.

PMID- 12007795
TI  - How does the mitochondrial ADP/ATP carrier distinguish transportable ATP and ADP
      from untransportable AMP and GTP?Dynamic modeling of the
      recognition/translocation process in the major substrate binding region.
AB  - To understand the transport mechanism of the bovine heart mitochondrial ADP/ATP
      carrier at the atomic level, we studied the four-dimensional features of the
      interaction of various purine nucleotides with the adenine nucleotide binding
      region (ABR) consisting of Arg(151)-Asp(167) in the second loop facing the matrix
      side. After three-dimensional modeling of ABR based on the experimental results,
      its structural changes on interaction with purine nucleotides were examined by
      molecular dynamics computation at 300 K. ATP/ADP were translocated to a
      considerable degree from the matrix side to the inner membrane region accompanied
      by significant backbone conformational changes, whereas neither appreciable
      translocation nor a significant conformational change was observed with the
      untransportable nucleotides AMP/GTP. The results suggested that binding of the
      terminal phosphate group and the adenine ring of ATP/ADP with Arg(151) and
      Lys(162), respectively, and subsequent interaction of a phosphate group(s) other
      than the terminal phosphate with Lys(162) triggered the expansion and subsequent
      contraction of the backbone conformation of ABR, leading to the translocation of
      ATP/ADP. Based on a simplified molecular dynamic simulation, we propose a dynamic
      model for the initial recognition process of ATP/ADP with the carrier.

PMID- 12007796
TI  - Molecular cloning and characterisation of p15(CDK-BP), a novel CDK-binding
      protein.
AB  - The suc1/Cks proteins are well-conserved regulatory components of cyclin
      dependent kinases 1 and 2 (CDK1/2). These small molecular mass proteins form a
      stable complex with CDK1/2 and are essential for normal regulation of CDKs during
      the cell division cycle and for degradation of p27(kip1). Despite the high degree
      of homology between the nine known CDKs, only CDK1, CDK2 and, to a lesser extent,
      CDK3 are able to bind to the suc1/Cks proteins. No additional suc1/Cks-related
      proteins interacting with other CDKs have been reported. We have purified, from
      starfish oocytes, a 15 kDa protein, p15(CDK-BP), which cross-reacts with anti-Cks
      antibodies (L. Azzi, L. Meijer, A.C. Ostvold, J. Lew, J.H. Wang, J. Biol. Chem.
      269 (1994)). Following microsequencing of internal peptides and generation of
      corresponding oligonucleotides we cloned two cDNAs encoding two closely related
      proteins, p15A and p15B. The predicted protein sequences display distant but
      distinct homology with the Suc1/Cks proteins, including the genuine starfish Cks
      homologue protein, p9(CksMg). P15 transcripts are essentially expressed in
      oocytes. Recombinant p15B or native p15(CDK-BP) bind a 34 kDa protein cross
      reacting with anti-PSTAIRE antibodies, a feature characteristic of CDK-related
      proteins. In addition p15B interacts tightly with CDK4, CDK6, CDK8 and the yeast
      CDC28-related kinase Pho85, but not with CDK1, CDK2 or CDK7. P15 does not appear
      to alter the catalytic activity of the bound kinases.

PMID- 12007797
TI  - Carbon catabolite repression in bacteria: choice of the carbon source and
      autoregulatory limitation of sugar utilization.
AB  - Carbon catabolite repression (CCR) in bacteria is generally regarded as a
      regulatory mechanism to ensure sequential utilization of carbohydrates. Selection
      of the carbon sources is mainly made at the level of carbohydrate-specific
      induction. Since virtually all carbohydrate catabolic genes or operons are
      regulated by specific control proteins and require inducers for high level
      expression, direct control of the activity of regulators or control of inducer
      formation is an efficient measure to keep them silent. By these mechanisms,
      bacteria are able to establish a hierarchy of sugar utilization. In addition to
      the control of induction processes by CCR, bacteria have developed global
      transcriptional regulation circuits, in which pleiotropic regulators are
      activated. These global control proteins, the catabolite gene activator protein
      (CAP), also known as cAMP receptor protein, in Escherichia coli or the catabolite
      control protein (CcpA) in Gram-positive bacteria with low GC content, act upon a
      large number of catabolic genes/operons. Since practically any carbon source is
      able to trigger global transcriptional control, expression of sugar utilization
      genes is restricted even in the sole presence of their cognate substrates.
      Consequently, CAP- or CcpA-dependent catabolite repression serves as an
      autoregulatory device to keep sugar utilization at a certain level rather than to
      establish preferential utilization of certain carbon sources. Together with other
      autoregulatory mechanisms that are not acting at the gene expression level, CCR
      helps bacteria to adjust sugar utilization to their metabolic capacities.
      Therefore, catabolic/metabolic balance would perhaps better describe the
      physiological role of this regulatory network than the term catabolite
      repression.

PMID- 12007798
TI  - Genetic organization of the lexA, recA and recX genes in Xanthomonas campestris.
AB  - A gene cluster containing lexA, recA and recX genes was previously identified and
      characterized in Xanthomonas campestris pathovar citri (X. c. pv. citri). We have
      now cloned and sequenced the corresponding regions in the Xanthomonas campestris
      pv. campestris (X. c. pv. campestris) and Xanthomonas oryzae pathovar oryzae (X.
      o. pv. oryzae) chromosome. Sequence analysis of these gene clusters showed
      significant homology to the previously reported lexA, recA and recX genes. The
      genetic linkage and the deduced amino acid sequences of these genes displayed
      very high identity in different pathovars of X. campestris as well as in X.
      oryzae. Immunoblot analysis revealed that the over-expressed LexA protein of X.
      c. pv. citri functioned as a repressor of recA expression in X. c. pv.
      campestris, indicating that the recombinant X. c. pv. citri LexA protein was
      functional in a different X. campestris pathovar. The abundance of RecA protein
      was markedly increased upon exposure of X. c. pv. campestris to mitomycin C, and
      an upstream region of this gene was shown to confer sensitivity to positive
      regulation by mitomycin C on a luciferase reporter gene construct. A symmetrical
      sequence of TTAGTAGTAATACTACTAA present within all three Xanthomonas lexA
      promoters and a highly conserved sequence of TTAGCCCCATACCGAA present in the
      three regulatory regions of recA indicate that the SOS box of Xanthomonas strains
      might differ from that of Escherichia coli.

PMID- 12007799
TI  - NADP-dependent isocitrate dehydrogenase from the halophilic archaeon Haloferax
      volcanii: cloning, sequence determination and overexpression in Escherichia coli.
AB  - A gene encoding NADP-dependent Ds-threo-isocitrate dehydrogenase was isolated
      from Haloferax volcanii genomic DNA by using a combination of polymerase chain
      reaction and screening of a lambda EMBL3 library. Analysis of the nucleotide
      sequence revealed an open reading frame of 1260 bp encoding a protein of 419
      amino acids with 45837 Da molecular mass. This sequence is highly similar to
      previously sequenced isocitrate dehydrogenases. In the alignment of the amino
      acid sequences with those from several archaeal and mesophilic NADP-dependent
      isocitrate dehydrogenases, the residues involved in dinucleotide binding and
      isocitrate binding are well conserved. We have developed methods for the
      expression in Escherichia coli and purification of the enzyme from H. volcanii.
      This expression was carried out in E. coli as inclusion bodies using the
      cytoplasmic expression vector pET3a. The enzyme was refolded by solubilisation in
      8 M urea followed by dilution into a buffer containing EDTA, MgCl(2) and 3 M
      NaCl. Maximal activity was obtained after several hours incubation at room
      temperature.

PMID- 12007800
TI  - Diversity of CTX-M beta-lactamases and their promoter regions from
      Enterobacteriaceae isolated in three Parisian hospitals.
AB  - Nine clinical isolates of Enterobacteriaceae (six Escherichia coli and three
      Proteus mirabilis) isolated in three Parisian hospitals between 1989 and 2000
      showed a particular extended-spectrum cephalosporin-resistance profile
      characterized by resistance to cefotaxime and aztreonam but not to ceftazidime.
      CTX-M-1, CTX-M-2, CTX-M-9, CTX-M-14 and two novel plasmid-mediated CTX-M beta
      lactamases (CTX-M-20, and CTX-M-21) were identified by polymerase chain reaction
      and isoelectric focusing (pI>8) and were associated in eight cases with TEM-1
      (pI=5.4) or TEM-2 (pI=5.6) beta-lactamases. We used internal ISEcp1 and IS26
      forward primers and the CTX-M consensus reverse primer to characterize the CTX-M
      beta-lactamase promoter regions and showed their high degree of structure
      diversity. We found upstream of some bla(CTX-M) genes, a 266-bp sequence 100%
      identical to the sequence upstream of the Kluyvera ascorbata beta-lactamase gene,
      suggesting that this chromosomal enzyme is the progenitor of the CTX-M-2/5
      cluster.

PMID- 12007801
TI  - Characterization of molecular markers for specific and sensitive detection of
      Botrytis cinerea Pers.: Fr. in strawberry (Fragariaxananassa Duch.) using PCR.
AB  - Random amplified polymorphic DNA (RAPD) assays were applied on 34 fungal strains
      isolated from strawberry and other host plants, in order to detect polymorphism
      to consequently identify and isolate molecular markers specific to Botrytis
      cinerea. Among the 26 10-mer primers tested, one primer mainly amplified a 750-bp
      product present in all the B. cinerea strains and absent in the other species and
      genera examined. This product was cloned and sequenced in order to design a
      specific 20-mer primer pair, which was tested on the 34 fungal isolates by
      polymerase chain reaction (PCR). A single 0.7-kb band was amplified in all the 13
      strains of B. cinerea isolated from different host plants. Moreover, a 0.6-kb
      band was amplified in both Botrytis fabae strains. No band was observed for the
      nine other Botrytis species and 12 fungal genera isolated from strawberry plants.
      A comparison between the 0.7-kb B. cinerea sequence and the 0.6-kb B. fabae
      sequence revealed 98% homology and one 122-bp deletion for B. fabae, including an
      EcoRI site. Hybridization of Southern blots with RAPD and EcoRI-digested DNA
      confirmed the specificity of the marker. The limit of detection of B. cinerea
      genomic DNA was approximately 0.2 pg. The PCR procedure was able to amplify the
      0.7-kb B. cinerea fragment form mixed samples of DNA as low as 2 pg B. cinerea
      genomic DNA and 1 microg plant DNA. Thus this PCR-based detection procedure is a
      powerful tool for diagnosis of B. cinerea in symptomless strawberry plants, and
      should allow infection and latency sites to be localized in order to improve
      knowledge of the epidemiology of the pathogen under field conditions.

PMID- 12007802
TI  - Strain-dependent effects of environmental signals on the production of
      extracellular phospholipase by Cryptococcus neoformans.
AB  - Extracellular phospholipase (PL) activities comprising phospholipase B,
      lysophospholipase and lysophospholipase transacylase have been identified in
      culture supernatants of Cryptococcus neoformans and contribute to virulence. We
      found that PL production was optimal after fungal growth at 30 degrees C and
      secretion at 37 degrees C for all six C. neoformans isolates studied (four C.
      neoformans var. neoformans and two C. neoformans var. gattii). No increase in PL
      activity was found in one strain, NU-2, in low iron or tissue culture media,
      conditions where upregulation of other virulence factors has been reported. The
      most virulent strains in an intravenous mouse model of infection were best able
      to produce PL at growth and secretion temperatures of 37 degrees C, in tissue
      culture media and under assay conditions of pH 7.0.

PMID- 12007803
TI  - LC-MS analysis of pig intestine sulfatides: interaction with Escherichia coli STb
      enterotoxin and characterization of molecular species present.
AB  - STb, a 48-amino acid thermostable enterotoxin is produced by enterotoxigenic
      Escherichia coli strains and is responsible for diarrheal diseases in many
      animals, including man. Our laboratory recently identified a family of molecules,
      from a lipid extract of porcine intestinal epithelial cells, that could bind to
      STb. These molecules were identified as sulfatides as they reacted with a
      monoclonal antibody raised against this family of molecules. However, as the
      epitope recognized by this monoclonal antibody was the galactose 3-sulfate, a
      doubt could remain as to the exact nature of the identified receptors. The goal
      of this study was thus to confirm the chemical nature of the STb-binding molecule
      as sulfatides or as distinctive molecules comprising a sulfated galactosyl
      residue. Using a thin-layer chromatography-overlay method we confirmed using
      antibodies to STb that STb recognizes the commercial sulfatides and a band
      migrating at the same level from the intestinal tissue lipid extract obtained
      from an 8-week-old piglet. The compounds recovered from the silica gel plates
      were analyzed by mass spectrometry in electrospray negative-ionization mode. The
      most abundant ions observed had m/z values of 779, 795, 879 and 907. For
      commercial bovine brain sulfatides the ions 795, 879 and 907 have been attributed
      to hydroxylated sulfatides with a saturated fatty acid chain containing 16, 22
      and 24 carbons, while the 779 ion contained a saturated fatty acid chain of 16
      carbons. The general profile of the ions observed was similar to the already
      described commercial bovine brain sulfatides.

PMID- 12007804
TI  - Cytochromes c of Acidithiobacillus ferrooxidans.
AB  - The chemolithoautotrophic Gram-negative bacterium Acidithiobacillus ferrooxidans
      is versatile and can grow on a number of electron donors and acceptors. In the A.
      ferrooxidans ATCC 23270 genome, computer analysis identified 11 genes encoding
      putative cytochromes c. At least eight putative cytochromes c were differentiated
      on gels in ATCC 33020 cells grown on ferrous iron or sulfur. All these
      cytochromes were associated with the inner or the outer membranes. Lower levels
      of total cytochromes c were observed in sulfur- than in ferrous iron-grown cells.
      One cytochrome c was specific for sulfur conditions while three were specific for
      iron conditions, suggesting that cytochrome c synthesis is modulated depending on
      the electron donor.

PMID- 12007805
TI  - Protein glycosylation in Haloferax volcanii: partial characterization of a 98-kDa
      glycoprotein.
AB  - The plasma membrane of Haloferax volcanii contains several glycoproteins,
      including a 98-kDa species. Using lectin-based chromatography, the glycoprotein
      was isolated and partially characterized. Sequence comparison, based on antibody
      binding as well as one-dimensional peptide maps show that the 98-kDa glycoprotein
      is distinct from the S-layer glycoprotein, the major glycoprotein in H. volcanii.
      The 98-kDa glycoprotein can be further distinguished from the S-layer
      glycoprotein on the basis of membrane attachment. Unlike the S-layer
      glycoprotein, the 98-kDa glycoprotein is not associated with the membrane in a
      Mg2+-dependent manner. Both proteins, however, apparently rely on a similar
      mechanism of glycosylation, since neither was affected by treatment with
      bacitracin or tunicamycin, agents known to interfere with protein glycosylation
      in other species. Finally, the pattern of glycosylation of the 98-kDa
      glycoprotein is not shared by a 95-kDa glycoprotein of the related Haloferax
      mediterranei strain.

PMID- 12007806
TI  - Peptide inhibitors of appressorium development in Glomerella cingulata.
AB  - The phytopathogen Glomerella cingulata (anamorph: Colletotrichum gloeosporioides)
      infects host tissue by means of a specialised infection structure, the
      appressorium. The Saccharomyces cerevisiae alpha-mating factor pheromone, the
      Saccharomyces kluyveri alpha-mating factor pheromone and a hendecapeptide
      produced by G. cingulata inhibit appressorium development. The amino acid
      sequence of the G. cingulata peptide, GYFSYPHGNLF, is different from that of the
      mature pheromone peptides of other filamentous fungi. The peptide has sequence
      similarity with the Saccharomyces alpha-mating factor pheromones, but is unable
      to elicit growth arrest in S. cerevisiae.

PMID- 12007807
TI  - Efflux of chloramphenicol by the CmlA1 protein.
AB  - The cmlA1 gene cassette contains the cmlA1 gene, that confers resistance to
      chloramphenicol, as well as a promoter and translational attenuation signals, and
      expression of cmlA1 is inducible by low concentrations of chloramphenicol. The
      CmlA1 protein encoded by cmlA1 was localised in the inner membrane. Active efflux
      of chloramphenicol, additional to the endogenous efflux from Escherichia coli
      cells, was observed when the cmlA1 gene was present and the production of CmlA1
      had been preinduced with subinhibitory concentrations of chloramphenicol. Both
      endogenous and CmlA1-mediated export of chloramphenicol was driven by the proton
      motive force.

PMID- 12007808
TI  - Construction and initial characterization of a luminescent Synechococcus sp. PCC
      7942 Fe-dependent bioreporter.
AB  - A Synechococcus sp. PCC 7942 bioreporter strain capable of sensing bioavailable
      Fe was constructed by fusing the Fe-responsive isiAB promoter to the Vibrio
      harveyi luxAB genes. Monitoring luxAB-dependent luminescence through the growth
      curve demonstrated that in Fe-replete media, transcription from the isiAB
      promoter was induced transiently in the mid-exponential phase of growth. The
      initiation of transcription was the functional response to a 10-fold depletion of
      intracellular Fe to approximately 12 amol Fe per cell. Constitutive isiAB
      dependent transcription was observed in Fe-depleted growth media. A dose-response
      relationship of the bioreporter was generated using trace metal-buffered Fraquil
      medium and was best represented by a sigmoidal curve having a linear component
      extending between pFe 21.1 (Fe3+=10(-21.1) M) and pFe 20.6 (Fe3+)=10(-20.6) M).
      Initial field trials conducted using water sampled from Lake Erie demonstrate
      that the bioreporter can serve as a quantitative tool to assess Fe deficiency in
      natural freshwater environments.

PMID- 12007809
TI  - Identification of lysine-78 as an essential residue in the Saccharomyces
      cerevisiae xylose reductase.
AB  - Yeast xylose reductases are hypothesized as hybrid enzymes as their primary
      sequences contain elements of both the aldo-keto reductases (AKR) and short chain
      dehydrogenase/reductase (SDR) enzyme families. During catalysis by members of
      both enzyme families, an essential Lys residue H-bonds to a Tyr residue that
      donates proton to the aldehyde substrate. In the Saccharomyces cerevisiae xylose
      reductase, Tyr49 has been identified as the proton donor. However, the primary
      sequence of the enzyme contains two Lys residues, Lys53 and Lys78, corresponding
      to the conserved motifs for SDR and AKR enzyme families, respectively, that may H
      bond to Tyr49. We used site-directed mutagenesis to substitute each of these Lys
      residues with Met. The activity of the K53M variant was slightly decreased as
      compared to the wild-type, while that of the K78M variant was negligible. The
      results suggest that Lys78 is the essential residue that H-bonds to Tyr49 during
      catalysis and indicate that the active site residues of yeast xylose reductases
      match those of the AKR, rather than SDR, enzymes. Intrinsic enzyme fluorescence
      spectroscopic analysis suggests that Lys78 may also contribute to the efficient
      binding of NADPH to the enzyme.

PMID- 12007810
TI  - Activity of the Streptomyces coelicolor stress-response sigma factor sigmaH is
      regulated by an anti-sigma factor.
AB  - The alternative sigma factor sigmaH has been shown to play an important role in
      stress response and morphological differentiation in Streptomyces coelicolor. Its
      gene, sigH, is located in an operon with the gene encoding proposed anti-sigma
      factor UshX, and one of the promoters directing expression of the operon is
      dependent upon sigH. To clarify the function of S. coelicolor UshX, both the
      sigmaH and UshX proteins were overproduced in Escherichia coli and purified. In
      an in vitro transcription assay, sigmaH, after complementation with S. coelicolor
      core RNA polymerase, was able to recognize the sigH-dependent promoter, sigH-P2.
      This transcription was inhibited by UshX, if it was incubated with sigmaH prior
      to the addition of the core RNA polymerase. When sigmaH and UshX were incubated
      and electrophoresed through non-denaturing polyacrylamide gels, they formed a
      specific complex. These results showed that UshX is a specific anti-sigma factor
      for sigmaH, and the S. coelicolor sigH operon is directly autoregulated.

PMID- 12007811
TI  - Production of PHA depolymerase A (PhaZ5) from Paucimonas lemoignei in Bacillus
      subtilis.
AB  - Purification of poly(3-hydroxybutyrate) depolymerase (EC 3.1.1.75) from
      Paucimonas lemoignei is complicated because the bacterium produces several
      isoenzymes which are difficult to separate from each other. The phaZ5 gene of P.
      lemoignei encoding extracellular poly(3-hydroxybutyrate) depolymerase A was
      functionally expressed from the constitutive P43 promoter of pWB980 in a multiple
      protease-negative mutant of Bacillus subtilis (strain WB800) and secreted to the
      culture medium. The depolymerase (apparent M(r), 42 kDa; 1.9 mg purified protein
      per liter culture) was purified from cell-free culture fluid to homogenity by
      applying only one chromatography step in comparison to at least two necessary
      steps if poly(3-hydroxybutyrate) depolymerases are purified from P. lemoignei.
      The recombinant depolymerase lacked any carbohydrate content in contrast to the
      glycosylated depolymerase of the wild-type. Glycosylation was not essential for
      activity but enhanced the thermal stability of the enzyme at high temperature.
      Overexpression of poly(3-hydroxybutyrate) depolymerase in B. subtilis is more
      efficient than in Escherichia coli.

PMID- 12007812
TI  - Transformation using in vivo and in vitro methylation in Streptomyces griseus.
AB  - Streptomyces griseus does not readily take up foreign DNA isolated from other
      Streptomyces species or Escherichia coli, presumably due to its unique
      restriction-modification systems that function as a barrier for interspecific DNA
      transfer. To efficiently transform S. griseus by avoiding the restriction
      barriers, we methylated incoming DNA in vivo and in vitro and treated protoplasts
      with heat prior to transformation. Whereas heat treatment of protoplasts or
      methylation of the E. coli-Streptomyces shuttle vectors (pXE4 and pKK1443) did
      not prominently improve the transformation efficiency, HpaII methylation of the
      vectors from any E. coli strains tested in this study highly increased the
      transformation efficiency. The highest transformation efficiency was observed
      when the shuttle vectors were isolated from the dam, hsd strain of E. coli
      (GM161) and methylated by AluI and HpaII methyltransferases, and the efficiency
      was approximately the same as that of the vectors from S. griseus. We identified
      several restriction-modification systems that decrease the transformation
      efficiency. This research also led us to understand methylation profiles and
      restriction-modification systems in S. griseus.

PMID- 12007813
TI  - Clonality structure in Candida dubliniensis.
AB  - Multilocus enzyme electrophoresis was performed on 76 European strains of Candida
      dubliniensis. Ten of the 20 enzyme-encoding loci were polymorphic, giving rise to
      10 electrophoretic types within the sample studied. Investigation of the
      population genetics of a subset of 36 strains from HIV-infected patients in
      London showed the existence of strong heterozygote deficits and excesses
      associated with significant linkage disequilibria between pairs of loci. These
      findings, together with the predominance of multilocus genotypes, strongly
      suggest that C. dubliniensis is mainly (if not totally) clonal. Analysis of
      genotypes of a larger number of strains should confirm this conclusion and
      improve our understanding of the epidemiology of this pathogen.

PMID- 12007814
TI  - Recurrent intragenomic recombination leading to sequence homogenization during
      the evolution of the lipoyl-binding domain.
AB  - The lipoyl-binding domain is often present, in one or several copies, in the E2
      subunit and, less often, in the E1 and E3 subunits of 2-oxo acid dehydrogenase
      complexes. Phylogenetic analysis shows evidence of multiple, independent
      intragenomic recombination events between different versions of the lipoyl
      binding domain in various bacteria and eukaryotic mitochondria, leading to
      homogenization of the sequences of the lipoyl-binding domain within the same
      enzymatic complex in several bacterial lineages. This appears to be the first
      case of sequence homogenization at the level of an individual domain in
      prokaryotes.

PMID- 12007815
TI  - Identification of a novel mycobacterial transcriptional regulator and its
      involvement in growth rate dependence and stringent control.
AB  - A novel transcriptional regulator has been identified in the 400-bp upstream
      region of the guaA gene of Mycobacterium tuberculosis H37Rv that promotes the
      expression of lacZ gene in Mycobacterium smegmatis mc(2)155 and M. tuberculosis
      H37Rv but not in Escherichia coli DH5alpha. PCR-mediated deletion mutagenesis and
      cloning identified a 120-bp fragment upstream from the guaA gene to be the actual
      regulator. Primer extension analysis mapped the transcription start site to be
      the first 'G' residue of the translation start codon GTG of the guaA gene.
      Electrophoretic mobility shift assay showed strong binding of M. smegmatis RNA
      polymerase holoenzyme to the 400-bp fragment that expresses lacZ in mycobacterial
      species and a weak binding to the 280-bp fragment that expresses only in E. coli
      DH5alpha. Both promoter recombinants revealed varied response in the presence of
      purine nucleotides and exhibited down-regulation when subjected to amino acid
      starvation.

PMID- 12007816
TI  - An IS900-like sequence found in a Mycobacterium sp. other than Mycobacterium
      avium subsp. paratuberculosis.
AB  - The insertion sequence IS900 has been considered specific for Mycobacterium avium
      subsp. paratuberculosis (M. paratuberculosis) and has, therefore, been used as
      the target gene for diagnostic PCR of M. paratuberculosis. From a healthy dairy
      cow we have isolated and characterised a mycobacterium harbouring one copy of a
      sequence with 94% identity to IS900 at the nucleic acid level. The isolate was
      shown to be related to Mycobacterium cookii, as assessed by 16S rRNA sequencing.
      Strong amplifications were obtained with several PCR primers described for
      detection of IS900. This finding shows the need of alternative PCR systems based
      on other genes than IS900 to confirm the presence of M. paratuberculosis.

PMID- 12007817
TI  - Transformation of the medicinal basidiomycete Trametes versicolor to hygromycin B
      resistance by restriction enzyme mediated integration.
AB  - Trametes versicolor, a white-rot basidiomycete, degrades cellulose and lignin as
      well as many recalcitrant chemicals. There have been many reports about the
      cloning of laccase and peroxidase genes of T. versicolor which are involved in
      lignin degradation. In order to analyze a gene function and introduce foreign
      genes into an organism, genetic transformation is required. Here we have
      successfully transformed T. versicolor to hygromycin B resistance using pAN 7-1
      plasmid by restriction enzyme mediated integration and have obtained many mutants
      in peroxidase activity and growing patterns. The transformation frequency was 25
      50 transformants (microg plasmid DNA)(-1). The transformants were quite stable
      after 10 consecutive transfers in non-selectable medium.

PMID- 12007818
TI  - Cloning and characterization of vmaA, the gene encoding a 69-kDa catalytic
      subunit of the vacuolar H+-ATPase during alkaline pH mediated growth of
      Aspergillus oryzae.
AB  - Screening of a cDNA library constructed under alkaline pH mediated growth of
      Aspergillus oryzae implicated a vacuolar H+-ATPase gene (vmaA) as a putative
      candidate involved in alkaline pH adaptation. A. oryzae vmaA genomic DNA extended
      to 2072 bp including three introns and encoded a protein of 605 amino acids.
      VmaAp was homologous to Vma-1p from Neurospora crassa (71%), Vma1p from
      Saccharomyces cerevisiae (69%) and ATP6A2 from human (49%). The vmaA cDNA
      complemented S. cerevisiae V-ATPase disrupted strain (Deltavma1) was viable at
      alkaline pH 8.0 and in the presence of CaCl(2) (100 mM). Northern analysis
      revealed an enhanced expression of vmaA during growth of A. oryzae in alkaline
      medium (pH 10.0). The A. oryzae vmaA disruptant exhibited abnormally shrunken
      vacuoles and hyphal walls at pH 8.5 and a growth defect at pH 10.0, implicating
      an alkaline pH stress responsive role for vmaA in A. oryzae.

PMID- 12007819
TI  - Both transferrin binding proteins are virulence factors in Actinobacillus
      pleuropneumoniae serotype 7 infection.
AB  - Three genetically defined Actinobacillus pleuropneumoniae serotype 7 mutants with
      deletions in the small (tbpB), the large (tbpA), and both transferrin binding
      protein genes were constructed and examined in an aerosol infection model.
      Neither mutant caused clinical disease or could be reisolated, and no immune
      response could be detected 21 days after infection. This result clearly implies
      that each transferrin binding protein on its own is a virulence factor of A.
      pleuropneumoniae serotype 7.

PMID- 12007820
TI  - Activity of the enzymes involved in the synthesis of exopolysaccharide precursors
      in an overproducing mutant ropy strain of Streptococcus thermophilus.
AB  - The activities of some enzymes belonging to the Leloir pathway,
      phosphoglucomutase, UDP-glucose pyrophosphorylase, UDP-galactose 4-epimerase and
      galactose 1-P uridyl transferase, were studied in a wild ropy, a non-ropy and an
      overproducing mutant ropy strain of Streptococcus thermophilus. These activities
      were assayed over successive culture transfers along with exocellular
      polysaccharide (EPS) production. The overproducing mutant ropy strain showed
      increments in polysaccharide production over successive culture transfers, as
      opposed to reductions in production by the wild ropy strain. The observed
      variations among strains in the enzyme activities that were analysed in relation
      to EPS production suggest their involvement in the synthesis of sugar-nucleotide
      EPS precursors.

PMID- 12007821
TI  - Quantitative analysis of phytopathogenic ascomycota on leaves of pedunculate oaks
      (Quercus robur L.) by real-time PCR.
AB  - Leaves of oak trees are often infected by various pathogenic fungi. As it is
      difficult to remove such organisms quantitatively from the leaf surface and as it
      is often impossible to grow these organisms independently from their host, there
      are almost no molecular data available from these oak leaf specific pathogens.
      For the quantitative removal of the microorganisms a procedure was developed
      combining a wax and microorganism freezing method with a DNA extraction
      technique. For the development of a species specific detection, DNA of pathogenic
      filamentous fungi was isolated from hyphae of the upper leaf surface of Quercus
      robur. Three different species could be identified as (i) Cladosporium sp., (ii)
      Ramularia sp. and (iii) Microsphaera alphitoides by amplifying and sequencing an
      18S-28S segment of their rDNA. For the final quantification a real-time PCR
      protocol was established allowing the species specific quantification of the
      three pathogenic filamentous fungi. The whole procedure was successfully applied
      to quantify the amount of the three species on oak leaves collected in autumn.

PMID- 12007822
TI  - Expression of anthrax lethal factor gene by osmolyte induction.
AB  - The anthrax toxin consists of protective antigen (PA), lethal factor (LF) and
      edema factor (EF). PA mediates the entry of LF and EF to the cytosol where they
      exert their effects. Although PA is the major component of the vaccines against
      anthrax, LF has also been found to play an important role in enhancing protective
      immunity. We have developed an osmolyte-inducible LF expression system. The
      protein expression system contributed no additional amino acids to the
      recombinant LF making it suitable for the human vaccine trials.

PMID- 12007823
TI  - Reductive deamination as a new step in the anaerobic microbial degradation of
      halogenated anilines.
AB  - In this paper we report the isolation and characterization of an anaerobic
      enrichment culture as well as of a Rhodococcus sp. strain 2 capable of degrading
      3,4-dihaloanilines under nitrate reducing conditions. Using mass spectrometry
      several of the intermediates formed in the process of 3,4-dichloroaniline
      conversion were identified. Most interesting is the observation of reductive
      deamination and the formation of 1,2-dichlorobenzene as one of the intermediates.
      Using 19F NMR and fluorinated 3,4-dihaloaniline model substrates it was
      corroborated that reductive deamination of the anilines to give dihalobenzene
      intermediates represents a new initial step in the anaerobic microbial
      degradation of these halogenated anilines.

PMID- 12007824
TI  - Detection of methanotrophs with highly divergent pmoA genes from Arctic soils.
AB  - Tundra soil samples from the Canadian Arctic community, Kuujjuaq, were analyzed
      for the presence of the soluble (sMMO) and particulate (pMMO) methane
      monooxygenase genes. Total genomic DNA extracted from these soils was used as
      template for PCR using sMMO- and pMMO-specific primers, mmoX1-mmoX2 and A189
      A682, respectively. pMMO and sMMO genes were detected in the Kuujjuaq soil
      samples. Isolation of sMMO-possessing methanotrophic microorganisms from the
      three soils, as determined by the colony naphthalene oxidation assay, was carried
      out using direct plating (5 degrees C) and methane enrichment studies (5 degrees
      C and 25 degrees C). Direct plating did not yield sMMO-possessing methanotrophic
      bacteria, whereas methane enrichments yielded isolates possessing and expressing
      sMMO activity. Analysis of derived amino acid sequences of pmoA genes and partial
      16S rRNA genes obtained by PCR, using DNA isolated directly from this environment
      and from isolates, revealed the presence of highly divergent PmoA/AmoA sequences
      and 16S rRNA sequences that cluster closely with but are distinct from the genes
      from the genera Methylosinus and Methylocystis.

PMID- 12007826
TI  - Small conductance calcium-activated potassium channels of trout CNS: molecular
      structure, developmental expression, and partial biophysical characterization.
AB  - Two small conductance calcium-activated potassium channels that exhibited amino
      acid similarity with mammalian SK2 and SK3, respectively, were PCR cloned from
      the CNS of trout and sequenced. Upon heterologous expression in Sf21 insect cells
      trout SK2 (termed tSK2) produced a calcium-dependent, voltage-insensitive, and
      non-inactivating current with a single unit conductance of about 11 pS. This
      current was half maximally activated by 0.76 microM Ca(2+) and blocked by
      picomolar concentrations of apamin but not by TEA. Transcripts of both SK-related
      channels possessed a widespread distribution in the mature brain tissue of trout
      and outside the nervous system were detectable in muscle tissue as well as in
      liver. As revealed by RT-PCR analysis transcripts encoding tSK2 and tSK3 channels
      were early detectable during brain development (stage 30, shortly after
      hatching).

PMID- 12007827
TI  - Identification of differentially expressed genes induced by transient ischemic
      stroke.
AB  - We have used a rat model of focal cerebral ischemia to investigate changes in
      gene expression that occur during stroke. To monitor these changes, we employed
      representational difference analysis-polymerase chain reaction (PCR). A total of
      128 unique gene fragments were isolated, and we selected 13 of these for
      quantitative reverse transcriptase-PCR analysis. Of these 13 genes, we found
      seven that were differentially expressed. Four of these genes have not previously
      been implicated in stroke, and include neuronal activity regulated pentraxin
      (Narp), cysteine rich protein 61 (Cyr61), Bcl-2 binding protein BIS (Bcl-2
      interacting death suppressor), and lectin-like ox-LDL receptor (LOX-1). We
      demonstrated differential expression of each gene by quantitative PCR analysis,
      and in the case of LOX-1, we further confirmed differential expression by in situ
      hybridization. LOX-1 expression is induced greater than ten fold at the core
      lesion site, and is essentially localized to the ipsilateral half of the brain.
      LOX-1 appears to be expressed in a non-neuronal cell type, and it does not appear
      to be expressed in vascular endothelial cells within the brain. This suggests
      that LOX-1 may serve a novel function in the brain.

PMID- 12007828
TI  - Localization of pore-forming subunit of the ATP-sensitive K(+)-channel, Kir6.2,
      in rat brain neurons and glial cells.
AB  - Kir6.2, a subunit of the ATP-sensitive K(+) channel (K(ATP)), was localized in
      adult rat brain by immunohistochemistry and in situ hybridization. The Kir6.2
      mRNA was widely expressed in most rat brain neuronal populations and nuclei
      examined, intensely in the mitral cell layer and tufted cells of the olfactory
      bulb, pontine nucleus, pontine reticular nucleus, motor and spinal trigeminal
      nuclei and cuneate nuclei of the brain stem, moderately in the neocortex and
      cerebellar Purkinje cells, and weakly in the granular cell layer of the olfactory
      bulb and the granular layer of the cerebellum. In addition, glial cells also
      expressed the Kir6.2 gene weakly in the corpus callosum and cerebellar white
      matter. This wide localization of the gene was quite similar to that of Kir6.2
      protein. Double stainings with anti-GFAP and anti-Kir6.2 antibodies were
      performed in this study. Glial cells showing immunoreactivity to both anti-Kir6.2
      and anti-GFAP were confirmed to be astrocytes, and those showing only
      immunoreactivity to anti-Kir6.2 but not to anti-GFAP were presumed to be
      oligodendrocytes and confirmed by immunoelectron microscopy. Thus, it may be
      concluded that both oligodendrocytes and astrocytes contain Kir6.2. Under the
      electron microscope, we showed in vivo for the first time that the immunoreactive
      products were localized in the endoplasmic reticulum and Golgi apparatus as well
      as the plasma membranes of neurons and glial cells.

PMID- 12007829
TI  - Absence of pineal-independent mediation of seasonal differences in
      suprachiasmatic nucleus AVP and VIP mRNA expression in Siberian hamsters.
AB  - Assessment of seasonal variations in expression of brain neuropeptide mRNA is
      complicated by concurrent circadian variations. Because entrainment of
      suprachiasmatic nucleus (SCN) based rhythms differs in long versus short day
      lengths, valid seasonal comparisons must be made at equivalent circadian phases.
      We used a novel experimental design which permitted sampling at identical
      circadian phases of animals exhibiting opposite seasonal reproductive responses
      to the same intermediate day length. This allowed us to test whether seasonal
      changes in arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP)
      mRNA expression in the SCN occur in the absence of the pineal gland. Juvenile
      Siberian hamsters were gestated and maintained postnatally in either a long
      photoperiod (16 h light/day) or short photoperiod (10 h light/day). At the time
      of weaning (18 days of age), the hamsters were pinealectomized and either
      transferred to a new photoperiod (10-, 16- or 14-h light/day) or left in the
      original photoperiod. Hamsters from 10L had substantially smaller and lighter
      testes than those from 16L. If photoperiodic modulation of AVP and VIP mRNA
      expression occurs in the absence of the pineal, then transfer of pinealectomized
      hamsters from a longer (16L) or shorter (10L) photoperiod to an intermediate
      photoperiod (14L) should result in a differential response with respect to SCN
      AVP and VIP mRNA expression but not testis size. When sampled at an identical
      circadian phase (3 h after lights on) in 14L there was no difference in the
      expression of AVP or VIP mRNA in the SCN between animals previously housed in
      long versus short day lengths. In contrast to a previous study that did not
      carefully control for circadian phase, the present findings suggest that seasonal
      photoperiodic control of SCN neuropeptide mRNA expression depends upon the pineal
      gland. In addition, the present findings demonstrate a significant, negative
      correlation between AVP mRNA expression in the SCN and the length of the daily
      active phase (alpha).

PMID- 12007830
TI  - G protein-coupled receptor kinases, beta-arrestin-2 and associated regulatory
      proteins in the human brain: postmortem changes, effect of age and subcellular
      distribution.
AB  - G protein-coupled receptor kinases (GRKs) and beta-arrestin-2 play a crucial role
      in the regulation of neurotransmitter receptors in brain. In this study, GRK2,
      GRK6, beta-arrestin-2 and associated regulatory proteins (Gbeta proteins and
      protein phosphatase (PP)-2A) were quantitated in human brains (immunodensity with
      specific antibodies) to assess for postmortem changes (pattern of protein
      degradation) and to investigate the effect of aging on these regulatory proteins
      as well as their subcellular distribution (cytosol and membrane fractions). In
      brain (prefrontal cortex, total homogenate) of healthy subjects (n=14) the
      immunodensities of GRK2 (r=-0.76), GRK6 (r=-0.64), beta-arrestin-2 (r=-0.57),
      Gbeta proteins (r=-0.59) and neurofilament (NF)-L (r=-0.64), but not PP-2A,
      declined markedly with the length of postmortem delay (PMD, 3-81 h). With these
      linear decay models, the average decreases per 12 h of PMD (from 12 to 72 h) were
      7-11% for the various proteins. The immunodensities of GRK2 (r=-0.71), GRK6 (r=
      0.61), and beta-arrestin-2 (r=-0.54) in human brain (n=12) also declined with
      aging (16 to 87 years) and the average decreases per decade (from 20 to 80 years)
      were 3-5%. In contrast, the immunodensities of PP-2A, Gbeta and NF-L in brain did
      not correlate significantly with the age of the subject at death (16-87 years).
      The immunodensities of GRK2/6 and beta-arrestin-2 showed marked individual
      variations and were strongly reduced after several freeze/thaw cycles. In the
      prefrontal cortex the subcellular distribution (cytosol/membrane) of the two GRKs
      differed markedly (GRK2: 60%/40%; GRK6: 5%/95%), and that of beta-arrestin-2 was
      as expected for a soluble protein (60%/40%). In brains of healthy subjects, the
      immunodensities of cytosolic GRK2 and beta-arrestin-2 correlated, respectively,
      with those of membrane-associated GRK2 (r=0.67, P=0.049, n=9) and membrane
      associated beta-arrestin-2 (r=0.77, P=0.01, n=9). The results of this study
      emphasize the importance of examining relevant variables (PMD, age) and potential
      artifacts (individual variation, freeze-thawing effect) when designing signal
      transduction studies in neuropsychiatric disorders using the postmortem human
      brain.

PMID- 12007832
TI  - Increased expression of mitochondrial respiratory enzymes in the brain of
      epilepsy-prone, naive EL mice.
AB  - The present studies demonstrate that expression of both type 5 and type 6
      subunits of NADH dehydrogenase and the type 1 subunit of cytochrome oxidase is
      enhanced significantly in the brains of naive, epilepsy-prone EL mice. In
      contrast, no apparent change in expression occurred with type 1 and type 2
      subunits of NADH dehydrogenase. When expression of type 5 and 6 subunits of NADH
      dehydrogenase was determined at 24 h after a single series of vestibular
      stimulation, significant down-regulation was detected. The expression of subunit
      2 of NADH dehydrogenase augmented gradually after vestibular stimulation. The
      increased expression of these mitochondrial respiratory enzymes may reflect
      enhanced demand for energy due to inherent, spontaneous neuronal hyperactivity in
      the brains of EL mice.

PMID- 12007831
TI  - Fatty acid synthase expression during peripheral nervous system myelination.
AB  - The expression of fatty acid synthase (FAS) in rat and mouse sciatic nerves
      during postnatal development was investigated. FAS activity was not sensitive to
      the nutritional status of the animals. During development, the specific activity
      of FAS was low in rat and mouse nerves immediately after birth. Then, there was a
      steady increase in the activity (8- to 10-fold) which reached a maximal level
      around postnatal day 11, plateaued till day 32, and decreased to reach 30% of the
      maximum at day 80. A similar developmental profile was obtained when the amount
      of FAS protein was quantified, thus suggesting that the variations in activity
      observed during sciatic nerve development are mainly due to variations in FAS
      protein content. Northern blot analysis showed that the mRNA levels for FAS
      parallels those of the ceramide galactosyl transferase (CGT) during mouse sciatic
      nerve development and in a rat demyelination-nerve regeneration model. In
      addition, we measured FAS expression in the sciatic nerves of the trembler
      mutant, which is a mouse model of PNS dysmyelination. In 20-day-old trembler
      nerves, FAS specific activity, protein amount and mRNA levels represented only
      25% of the normal values. Altogether, our data indicate that FAS expression is
      linked to the PNS myelination process, and that the main regulation occurs at the
      level of the gene expression.

PMID- 12007833
TI  - Localization of adenylyl cyclase proteins in the rodent retina.
AB  - The isoforms of adenylyl cyclase that mediate cyclic AMP signaling pathways in
      the retina are, for the most part, unknown. Therefore, the protein expression
      patterns of adenylyl cyclase isoforms in the rodent retina were characterized
      immunocytochemically using antibodies directed against Ca(2+)-stimulated (AC1,
      AC3 and AC8), Ca(2+)-inhibited (AC9) and Ca(2+)-insensitive (AC2, AC4, AC7)
      isoforms of adenylyl cyclase. The ganglion cell layer and the inner nuclear layer
      (INL) were immunoreactive for both Ca(2+)-sensitive (AC1, AC3) and Ca(2+)
      insensitive (AC2, AC4) isoforms of adenylyl cyclase. Antibodies against isoforms
      from all three classes of adenylyl cyclase labeled the inner plexiform layer. In
      the outer retina, antibodies against Ca(2+)-insensitive isoforms labeled
      photoreceptors and the outer plexiform layer (OPL). Radial elements in the ONL
      and INL were AC4-immunoreactive and the nerve fibre layer and optic nerve were
      AC2-, AC4- and AC9-immunoreactive. Antibodies against AC7 did not label rodent
      neural retina. These data indicate that there is a heterogeneous distribution of
      adenylyl cyclase isoforms throughout the rodent retina. Nonetheless, there is a
      general indication of a greater expression of Ca(2+)-insensitive adenylyl cyclase
      isoforms in the outer retina, particularly within photoreceptors.

PMID- 12007834
TI  - Modified GFAP promoter auto-regulates tet-activator expression for increased
      transactivation and reduced tTA-associated toxicity.
AB  - Transactivator tTA is a necessary component of the tetracycline-regulated
      inducible gene system. While several transgenic animals have been described that
      express tTA in the central nervous system (CNS), their tTA levels are often
      limited, presumably due to toxic effects. We evaluated methods for auto
      regulating tTA levels in astrocytes by modifying the transgenic promoter human
      GFAP (hGFAP). The hGFAP promoter carrying a single copy of the tet-operon in
      place of a native enhancer element (GFAPtetO1) drove expression of tTA at low
      levels during un-stimulated, basal condition. However the same promoter auto
      induced expression of tTA to significant levels after tetracycline withdrawal.
      Glial cell-specificity of the promoter remained uncompromised during both basal
      and induced conditions. Transgenic rats were developed using the auto-inducible
      GFAPtetO1 promoter that expressed tTA mRNA to high levels in the brain.
      Expression was widespread within the CNS but enriched in astrocyte-rich regions
      including the cerebellum. Primary cerebellar astrocytes from GFAPtetO1 rats
      transfected with 07LacZ produced substantially greater inducibility of reporter
      gene compared to GFAP-tTA transgenic rats. Finally, GFAPtetO1 rats exhibited
      severe motor/gait deficit when bred to homozygosity. This phenotype was
      attributable to developmental abnormalities of the cerebellum and was completely
      abrogated by doxycycline administration. These results suggest that developmental
      toxicity resulting from tTA expression can be circumvented and tTA transgenics
      with high transactivation potential can be developed using the auto-activation
      strategy. Promoter modification presented here may be useful in developing highly
      inducible transgenic strategies without loss in tissue-specificity.

PMID- 12007835
TI  - Change of gene expression profiles in the retina following optic nerve injury.
AB  - The purpose of the present study was to search for changes in gene expression
      patterns in the retina following optic nerve injury. We conducted a subtractive
      hybridization for comparison of the mRNAs in those retinas receiving optic nerve
      crush injury and those receiving sham operation. Both forward and reverse
      subtractions were carried out for 8-h and 24-h time points postoperatively.
      Resultant subtractive cDNA for each group was re-amplified and cloned to a
      plasmid. After DNA sequencing, the identity of subtractive cDNA was analyzed by
      blasting sequences to the Nonredundant gene database, Unigene database, and dbest
      database at NCBI. Thirty-four known genes and 32 EST were found in the forward
      subtractions. Forty-two known genes and 46 EST were found in reverse
      subtractions. Identities of the rest could not been found in the databases. To
      verify the subtractive results, RT-PCR was performed to test expression patterns
      of eight known genes found in the above analysis. Among these eight genes, seven
      demonstrated a statistically significant difference between the crushed eyes and
      the control eyes by quantitative image analysis. Together, our data show that
      expression of fatso, ephrin B2, NonO, Zfx, vitronectin, and XLRS increased after
      optic nerve injury, and expression of stathmin exhibited reduction after injury.

PMID- 12007836
TI  - The cannabinoid agonist DALN positively modulates L-type voltage-dependent
      calcium-channels in N18TG2 neuroblastoma cells.
AB  - The present study demonstrates a novel stimulatory effect of a cannabinoid
      agonist on calcium channels. DALN (1 nM) potentiated 45Ca(2+)-uptake by N18TG2
      neuroblastoma cells, an effect that was abolished by the specific CB1 receptor
      antagonist SR141716A. The stimulation of 45Ca(2+)-uptake by DALN was resistant to
      pertussis toxin (PTX), suggesting that Gi/Go GTP-binding proteins did not mediate
      this effect. Furthermore, PTX unmasked a stimulatory effect of a high
      concentration of DALN (1 microM), which by itself failed to stimulate calcium
      uptake in naive cells. The stimulatory effect of DALN on calcium entry to the
      cells was blocked by nicardipine but not by omega-conotoxin GVIA, indicating the
      entry of calcium through L-type voltage-dependent calcium channels. Blocking cAMP
      dependent protein kinase (PKA) by H-89 completely eliminated the elevation in
      calcium uptake, while blocking protein kinase C (PKC) by chelerythrine and
      calphostine-C only partially attenuated the stimulation. Blocking calmodulin by W
      7 revealed a similar partial inhibition of the stimulatory effect of DALN. Hence,
      we suggest a cannabinoid-specific, PTX-insensitive, stimulatory effect on L-type
      voltage-dependent calcium channels, which is mediated by PKA and modulated by PKC
      and calmodulin.

PMID- 12007837
TI  - VEGF mRNA expressed in microvessels of neonatal and adult rat cerebral cortex.
AB  - We measured mRNA levels of vascular endothelial growth factor (VEGF) and its Flk
      1/KDR receptor in isolated cerebral cortical microvessels and in the cerebral
      cortex of neonatal (1 week) and adult (11 week) rats using reverse transcription
      polymerase chain reaction (RT-PCR). Cerebral microvessels were isolated by
      density centrifugation, mesh filtration and passage through glass bead columns.
      The dominant cell types in this preparation are endothelial cells and pericytes.
      Among the four isoforms of VEGF mRNA expressed in these tissues, VEGF(165) was
      dominant (67% higher than VEGF(189) or VEGF(206)). All isoforms of VEGF were
      higher in adult cortical microvessels than in cortical homogenates. In isolated
      microvessels, VEGF mRNA for all isoforms combined was 70% higher in the neonate
      than in the adult. VEGF receptor Flk-1/KDR mRNA was also present in cortical
      microvessels and was higher in neonatal than in adult microvessels. The results
      suggest that VEGF is normally expressed in cerebral microvessels of both neonates
      and adults. Whether the source of VEGF is the endothelial cell or pericyte, will
      determine if VEGF has autocrine or paracrine actions. The results also support
      the hypothesis that microvascular cell turnover continues in the adult brain.

PMID- 12007838
TI  - Modulation of the membrane-binding projection domain of tau protein: splicing
      regulation of exon 3.
AB  - Tau is a microtubule-associated protein whose transcript undergoes complex
      regulated splicing in the mammalian nervous system. The N-terminal domain of the
      protein interacts with the axonal membrane, and is modulated by differential
      inclusion of exons 2 and 3. These two tau exons are alternatively spliced
      cassettes, in which exon 3 never appears independently of exon 2. Previous work
      with tau minigene constructs indicated that exon 3 is intrinsically suboptimal
      and its primary regulator is a weak branch point. In this study, we confirm the
      role of the weak branch point in the regulation of exon 3 but also show that the
      exon is additionally regulated by a combination of exonic enhancers and
      silencers. Furthermore, we demonstrate that known splicing regulators affect the
      ratio of exon 3 isoforms, Lastly, we tentatively pinpoint the site of action of
      several splicing factors which regulate tau exon 3.

PMID- 12007839
TI  - Changes in mRNA for choline transporter-like protein following facial nerve
      transection.
AB  - When the axon of a motoneuron is transected, axonal regrowth occurs to reconnect
      it to the correct target. During the regeneration period, a large amount of new
      membrane synthesis is required for the axons to extend. Choline is an important
      metabolite in all cells because of the major contribution of phosphatidylcholine
      and sphingomyelin to the production of membranes. Therefore, choline uptake is
      necessary for axonal elongation. We cloned rat choline transporter-like protein 1
      (rCTL1) as an upregulated gene in the axotomized facial motor nucleus by
      differential display polymerase chain reaction using adult rat facial nerve
      axotomy model. rCTL1 belongs to the choline transporter-like protein family,
      which takes up choline. We investigated the changes in rCTL1 mRNA levels in the
      facial motor nucleus of adult rats following axotomy by in situ hybridization. In
      the facial motoneurons signals of rCTL1 mRNA were rarely expressed, were
      transiently increased following axotomy and gradually returned to the control
      level. These results suggest that rCTL1 is involved in activated choline uptake
      for membrane synthesis in motoneurons following nerve transection.

PMID- 12007840
TI  - Axotomy does not up-regulate expression of sodium channel Na(v)1.8 in Purkinje
      cells.
AB  - Aberrant expression of the sensory neuron specific (SNS) sodium channel Na(v)1.8
      has been demonstrated in cerebellar Purkinje cells in experimental models of
      multiple sclerosis (MS) and in human MS. The aberrant expression of Na(v)1.8,
      which is normally present in primary sensory neurons but not in the CNS, may
      perturb cerebellar function, but the mechanisms that trigger it are not
      understood. Because axotomy can provoke changes in Na(v)1.8 expression in dorsal
      root ganglion (DRG) neurons, we tested the hypothesis that axotomy can provoke an
      up-regulation of Na(v)1.8 expression in Purkinje cells, using a surgical model
      that transects axons of Purkinje cells in lobules IIIb-VII in the rat. In situ
      hybridization and immunocytochemistry did not reveal an up-regulation of Na(v)1.8
      mRNA or protein in axotomized Purkinje cells. Hybridization and immunostaining
      signals for the sodium channel Na(v)1.6 were clearly present, demonstrating that
      sodium channel transcripts and protein were present in experimental cerebella.
      These results demonstrate that axotomy does not trigger the expression of
      Na(v)1.8 in Purkinje cells.

PMID- 12007841
TI  - Molecular cloning and expression of rat torsinA in the normal and genetically
      dystonic (dt) rat.
AB  - Deletions within the TOR1A gene cause early-onset (DYT1) torsion dystonia. We
      have cloned and sequenced the rat cDNA homologue of TOR1A and found a 91%
      identity with the human sequence. Northern blot analysis detects a single
      transcript of approximately 1.5 kb. In situ hybridization reveals a widespread
      distribution of torsinA mRNA within brain. No mutations were identified in the
      coding region of the gene in the genetically dystonic (dt) rat.

PMID- 12007842
TI  - Neuronal cells show regulatory differences in the hsp70 gene response.
AB  - The synthesis of heat shock proteins (Hsps), encoded by heat shock genes, is
      increased in response to various stress stimuli. Hsps function as molecular
      chaperones, they dissociate cytotoxic stress-induced protein aggregates within
      cells and ensure improved survival. Induction of heat shock genes is mainly
      regulated at the transcriptional level. The stress responsive transcription
      factor, heat shock factor 1 (HSF1), is involved in the transcriptional induction
      of the heat shock genes. Our objective was to examine how hsp70 genes are
      regulated in different transformed and primary neurons upon exposure to elevated
      temperature. Our findings reveal that the Hsp70 response is regulated at the
      translational level in Neuro-2a neuroblastoma cells, while the IMR-32
      neuroblastoma cells respond to stress by the classical HSF1-driven
      transcriptional regulatory mechanism. Primary rat hippocampal neurons show a lack
      of HSF1 and induction of the hsp70 gene. These observations suggest that neuronal
      cells display different hsp70 gene expression patterns which range from
      undetected response to transcriptional and posttranscriptional regulation during
      heat stress.

PMID- 12007843
TI  - New findings in beta-lactam and metronidazole resistant Bacteroides fragilis
      group.
AB  - Beta-lactam antibiotics and 5-nitroimidazoles have been extensively used against
      anaerobic bacteria. However, antibiotic resistance is increasingly common among
      anaerobic Gram-negative bacilli. The classical mechanisms of resistance to beta
      lactams are, (1) production of beta-lactamases; (2) alteration of penicillin
      binding proteins (PBPs); and (3) changes in outer membrane permeability to beta
      lactams. The 5-nitroimidazole molecule is a prodrug whose activation depends upon
      reduction of the nitro group in the absence of oxygen. Decreased uptake and
      altered reduction are believed to be responsible for metronidazole resistance.
      Five nim genes (A, B, C, D and E) have been identified in Bacteroides fragilis
      group spp. that confer resistance to 5-nitroimidazole antibiotics. Knowledge of
      the status and the mechanisms of resistance is critical for both the selection of
      antimicrobial therapy and the design of new antimicrobial agents. The purpose of
      this article is to review the mechanisms for and the prevalence of beta-lactam
      and metronidazole resistance in strains belonging to the B. fragilis group.

PMID- 12007844
TI  - Haemophilus influenzae in acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a common progressive respiratory
      disease that is associated with infective exacerbations that lead to worsening of
      symptoms. Many organisms are thought to trigger infective exacerbations, but
      Haemophilus influenzae is the most commonly isolated bacterium. The role of H.
      influenzae in infective exacerbations remains uncertain, mainly because the
      organism chronically colonises patients whose clinical condition is stable. H.
      influenzae may also comprise part of the normal nasopharyngeal flora in man,
      making the interpretation of positive cultures difficult in some cases.

PMID- 12007845
TI  - Investigation into the selection frequency of resistant mutants and the bacterial
      kill rate by levofloxacin and ciprofloxacin in non-mucoid Pseudomonas aeruginosa
      isolates from cystic fibrosis patients.
AB  - The frequency by which resistant Pseudomonas aeruginosa strains could be selected
      was compared for two antibiotics, levofloxacin and ciprofloxacin. Seven distinct
      strains were cultured on plates containing 1x, 2x, 4x and 8x the minimum
      inhibitory concentration (MIC) of the antibiotic under investigation. Resistant
      mutants were more readily isolated by growth on culture plates that contained
      ciprofloxacin, and the resulting MIC of the resistant mutant was also more
      frequently increased. Time-kill studies on comparable strains where the MIC for
      both antibiotics had increased by at least fourfold showed no difference between
      the two agents.

PMID- 12007846
TI  - Antimicrobial susceptibility of inducible AmpC beta-lactamase-producing
      Enterobacteriaceae from the Meropenem Yearly Susceptibility Test Information
      Collection (MYSTIC) Programme, Europe 1997-2000.
AB  - Among 11345 clinical isolates from 31 European centres in the MYSTIC (Meropenem
      Yearly Susceptibility Test Information Collection) Programme (1997-2000), the
      potential AmpC-producing pathogens were Enterobacter spp. (904 cases),
      Citrobacter spp. (144) and Serratia marcescens (288). Resistance to ceftazidime
      or cefotaxime (11-34%) and piperacillin/tazobactam (12%) was observed, indicating
      stably derepressed expression of AmpC cephalosporinases. Meropenem (MIC(90), 0.25
      mg/l; >99% susceptible) and imipenem (MIC(90), 2 mg/l; 98% susceptible) were
      active, even against these stably derepressed AmpC-producers: Enterobacter spp.
      (305 strains), Citrobacter spp. (29) and S. marcescens (35). The overall rank
      order of spectrum (% susceptible) versus the stably derepressed subset of
      isolates was: meropenem=imipenem (98%)>cefepime (89%)>gentamicin
      (73%)>ciprofloxacin (62%)>tobramycin (60%) >piperacillin/tazobactam (21%). We
      suggest increased attention in Europe to: (1) the recognition of these resistant
      phenotypes, (2) infection control practices, and (3) limiting the overuse of
      certain selecting extended-spectrum beta-lactam agents (e.g. ceftazidime).

PMID- 12007847
TI  - Change of pneumococcal resistance to antibiotics in adults between 1995 and 1997:
      a study in eight French counties.
AB  - The main object of this study was to describe the evolution of antibiotic
      resistance in pneumococci from adults, in eight French counties of France between
      1995 and 1997. Despite the high and increasing prevalence (23-35%) of pneumococci
      with diminished susceptibility to penicillin G (PSDP), resistance to amoxycillin
      (0.8-0.5%) and to cefotaxime (0-0.3%) was rare in both 1995 and 1997
      respectively. The percentage of pneumococci resistant to penicillin G (PRP,
      minimum inhibitory concentration >1 mg/l) remained stable between the two
      periods. PSDP showed increased resistance to macrolides (30-41%), to
      cotrimoxazole (28-34%) and to tetracycline (19-25%). These figures are lower than
      those obtained over the same periods and the same regions in children. The
      distribution of PSDP serotypes isolated in adults was the same as that seen in
      children: by descending order serotypes 23, 14, 9 and 6. This study by the
      Regional Pneumococcal Observatories confirms the high prevalence and the main
      characteristics of antibiotic resistance among pneumococci with variations in
      levels of resistance with the age of patients, with the site of sampling and from
      one Observatory to another.

PMID- 12007848
TI  - Growth of cell-wall-deficient variants of Enterobacter cloacae facilitates beta
      lactamase derepressed mutants.
AB  - The degree to which cell-wall-deficient bacteria (CWDB) are involved in the
      generation of beta-lactamase derepressed mutants (DM) was measured using
      Enterobacter cloacae 3624. The frequency of DM in non-permissive isotonic
      ticarcillin medium was compared with their frequency in hypertonic ticarcillin
      medium that supports CWDB growth. DM were resistant to extended spectrum
      penicillins and cephalosporins and had a basal beta-lactamase activity of >300
      units/mg protein. Anaerobic growth of CWDB increased the relative risk of DM 2 x
      10(6)-fold. Aerobic incubation produced fewer CWDB colonies but the risk of DM
      was still increased 400-fold over non-permissive controls. These results define a
      new role for CWDB as intermediaries in the emergence of resistance.

PMID- 12007849
TI  - Cefpirome sulphate for gynaecological infections and prophylaxis of non
      laparotomy surgery in patients with benign disease.
AB  - We organized a study group to conduct a clinical trial in patients with various
      gynaecological infections, and we also assessed the efficacy of a single dose of
      cefpirome sulphate as prophylaxis after vaginal hysterectomy. Cefpirome sulphate
      (CROM) was administered to 100 patients with gynaecological infections and the
      clinical and antibacterial efficacy was evaluated in 88 patients. The improvement
      rate was 77.0% (67/87) and the bacterial eradication rate 67.8% (40/59). Nineteen
      of the 210 patients enrolled in the comparison of CROM with cefmetazole sodium
      (CMET) prophylaxis developed postoperative infections. The incidence of infection
      showed no significant difference between the CROM group (n=11, 10.6%) and the
      CMET group (n=8, 7.5%) (P=0.56). Although these results suggest that CROM may be
      effective for the treatment of gynaecological infections and has a good safety
      profile, it was not superior to CMET as prophylaxis in women undergoing non
      laparotomy procedures at our hospital.

PMID- 12007850
TI  - Ceftriaxone activity against Gram-positive and Gram-negative pathogens isolated
      in US clinical microbiology laboratories from 1996 to 2000: results from The
      Surveillance Network (TSN) Database-USA.
AB  - Ceftriaxone was introduced into clinical practice in the USA in 1985 and was the
      first extended-spectrum (third-generation) cephalosporin approved for once-daily
      treatment of patients with Gram-positive or Gram-negative infections. Review of
      ceftriaxone activity is important given its continued use since the mid-1980s and
      reports of emerging resistance among all antimicrobial agent classes. We reviewed
      the activity of ceftriaxone and relevant comparative agents against five Gram
      positive and 11 Gram-negative species for a 5-year period, 1996-2000, using data
      from The Surveillance Network (TSN) Database-USA. All MIC results were
      interpreted using NCCLS breakpoint criteria. Ceftriaxone resistance among
      isolates of Streptococcus pneumoniae (n=17219) remained essentially unchanged
      over the 5 years studied and in fact was lower from 1998 to 2000 (5.0-5.1%) than
      in 1996 (6.3%) and 1997 (6.6%). Ceftriaxone resistance (range, 5.1-6.9%) among
      viridans group streptococci (n=6621) varied by <2% from 1997 to 2000. Beta-lactam
      resistant Streptococcus pyogenes (n=935) and group B beta-haemolytic streptococci
      (n=2267) were not identified in any year. Among methicillin-susceptible
      Staphylococcus aureus (n=39 284) ceftriaxone resistance was 0.1-0.3% per year
      from 1996 to 2000. Ceftriaxone resistance among Escherichia coli (n=472407;
      range, 0.2-0.4%), Klebsiella oxytoca (n=16231; range, 3.5-4.8%), Klebsiella
      pneumoniae (n=117754; range, 1.9-2.6%), Proteus mirabilis (n=67692; range, 0.2
      0.3%), Morganella morganii (n=11251; range, 0.3-2.1%) and Serratia marcescens
      (n=26519; range, 1.6-3.8%) was low and consistent from 1996 to 2000. Resistance
      to ceftriaxone among Enterobacter cloacae (n=48114; range, 21.7-23.9%) was
      relatively high, compared with other Enterobacteriaceae, but unchanged from 1996
      to 2000. Rates of resistance to ceftriaxone among Acinetobacter spp. (n=20813)
      increased from 24.8% in 1996 to 45.1% in 2000. All Haemophilus influenzae
      (n=7911) and Neisseria gonorrhoeae (n=218) were susceptible to ceftriaxone, as
      were 99.7% of Moraxella catarrhalis (n=312) tested in 1996 and 1997. In summary,
      ceftriaxone has retained its potent activity against the most commonly
      encountered Gram-positive and Gram-negative human pathogens despite widespread
      and ongoing clinical use for more than 15 years.

PMID- 12007851
TI  - A comparison of antibiotic susceptibility testing methods for cotrimoxazole with
      Burkholderia pseudomallei.
AB  - Melioidosis is caused by the Gram-negative soil saprophyte, Burkholderia
      pseudomallei and is endemic in tropical and subtropical regions of southeast Asia
      and northern Australia. Cotrimoxazole has been traditionally used for the therapy
      of melioidosis despite results indicating resistance often produced in the disc
      diffusion test against B. pseudomallei. This inconsistency was addressed by
      comparing this method with the agar dilution, MicroScan and E-test methods. The
      results demonstrated that by disc diffusion, 41.3% of 80 B. pseudomallei clinical
      isolates tested were susceptible to cotrimoxazole, whereas the MicroScan, agar
      dilution and the E-test demonstrated 92.5, 90 and 97.5% of the isolates to be
      susceptible, respectively. These results indicate that an MIC based method is
      required to test the susceptibility of B. pseudomallei against cotrimoxazole.

PMID- 12007852
TI  - Susceptibility patterns of Gram-negative bacteria from a Polish intensive care
      unit, 1997-2000.
AB  - The susceptibility of Gram-negative bacterial strains (n=400) isolated from
      clinical specimens of children hospitalized in a Polish intensive care unit (ICU)
      between 1997 and 2000 was tested. Meropenem, imipenem and ciprofloxacin were most
      active (>90% susceptibility) against the tested isolates, with no observed
      reduction in activity over 4 years. Extended-spectrum beta-lactamases and AmpC
      beta-lactamase producers among Enterobacteriaceae isolates from this ICU
      continued to be a serious therapeutic problem, although the carbapenems were
      highly active against these resistance phenotypes. Resistance to aminoglycosides
      (gentamicin, tobramycin) and ceftazidime was a characteristic of >40% of tested
      isolates.

PMID- 12007853
TI  - Dual dosage individualization of vancomycin therapy to treat Staphylococcus
      epidermidis intraperitoneal vascular paraprosthetic abscesses.

PMID- 12007854
TI  - Local immunotherapy with rhTNF-alpha mutein induces strong antitumor activity
      without overt toxicity--a review.
AB  - Tumor necrosis factor (TNF-alpha) is a cytokine possessing antitumor and
      immunomodulatory properties. The studies reviewed in the present paper evaluate
      the effect of intratumor or intraperitoneal (i.t./i.p.) injections of human
      recombinant TNF-alpha (rhTNF-alpha) and its derivatives (muteins V and VI) on the
      course of experimental tumors. The aim of local cytokine administration was to
      avoid or reduce the induction of undesired systemic symptoms. Although total
      remissions were not observed in the studies, morphological analysis of lung
      tissue, accepted as the toxicity index of the cytokines, showed that rhTNF-alpha
      produced the least side effects. Mutein V selectively binds to p55R receptor and
      at the same time exhibits high antitumor activity. These results confirm the
      usefulness of studies on the structurally altered rhTNF-alpha derivatives,
      produced by means of genetic engineering techniques, which bind selectively to
      different cellular receptors of TNF-alpha and show similar or stronger antitumor
      activity compared with a native molecule, without inducing undesired symptoms.

PMID- 12007855
TI  - Blood and spleen lymphocytes as targets for immunotoxic effects in the rat--a
      comparison.
AB  - Traditionally, immunotoxicological studies in the rat have been performed by
      measuring the effect of chemical substances on spleen lymphocytes in vivo and in
      vitro. However, rat blood lymphocytes may be more relevant than spleen cells for
      comparison with human blood lymphocytes. Further, lymphocytes in blood may be a
      more sensitive indicator of immunotoxic effects than spleen lymphocytes. Finally,
      in longitudinal studies peripheral blood specimens can be collected repeatedly
      from the same animals, thereby reducing the number of animals sacrificed and,
      possibly, experimental variation. We compared blood and spleen lymphocyte
      parameters in rats treated with a single dose of the immunosuppressant
      cyclophosphamide (CY), monitoring effects on blood and spleen lymphocytes by
      immunophenotyping. We also performed repeated bleedings to demonstrate the
      feasibility of following the time course of induced changes in the same animals.
      Immunophenotyping as well as total mononuclear cell counts consistently showed as
      large or lager effects of CY in blood lymphocytes than in spleen cells. Further,
      the measured effects in blood lymphocytes became statistically significant at an
      earlier time point, compared to spleen cells. Repeated bleedings of the same
      animals illustrated that blood specimens drawn from a peripheral vein give
      sufficient numbers of cells to perform immunotoxicological tests.

PMID- 12007856
TI  - Immunological and physiological effects of chronic exposure of Peromyscus
      leucopus to Aroclor 1254 at a concentration similar to that found at contaminated
      sites.
AB  - Polychlorinated biphenyls (PCBs) are environmental contaminants known to cause
      adverse health effects to biological systems. Limited data are available on their
      effects on the immune system of wildlife species. Previously, we found that 4 and
      6-week-old white-footed mice (Peromyscus leucopus) born from dams injected with a
      single dose (300 mg/kg) of Aroclor 1254, had altered immunological,
      hematological, and biochemical responses. Here, we examined the effect of
      transplacental, lactational and postnatal exposure to Aroclor 1254, at a
      concentration similar to that found at contaminated sites, on various
      physiological parameters of 22-week-old white-footed mice. Liver weight and liver
      somatic index of PCB treated animals were significantly higher, the combined
      weights of the adrenal glands were significantly lower and EROD and BROD enzyme
      activity was significantly higher compared to control values. The number of
      thymocytes of the treated mice was significantly lower than that of the controls;
      however, thymocytes of treated mice had a higher proliferative response to the
      mitogen Con A. These alterations were correlated with the PCBs body burdens. Some
      toxic effects of chronic exposure to PCBs, at levels comparable to exposure found
      in contaminated sites in the USA, are still evident in adult P. leucopus.

PMID- 12007857
TI  - Developmental toxicity but no immunotoxicity in the rat after prenatal exposure
      to diethylstilbestrol.
AB  - Studies with dioxins and PCB's have shown that the developing immune system may
      be especially vulnerable to xenobiotics during the perinatal period. However,
      current guidelines for reproductive toxicity testing do not include immune
      parameters. In the present study, we have explored the usefulness of including
      immune parameters within the prenatal developmental toxicity study in rats, using
      the treatment protocol as described in the OECD 414 developmental toxicity test
      guideline. In addition, the experimental protocol was enhanced by including ten
      dose groups to facilitate dose-response analysis. Diethylstilbestrol (DES) was
      used as the model compound, as it is known to be toxic both for embryofetal
      development and for the immune system. The results show developmental toxicity in
      terms of decreased fetal survival and decreased pup body weight in the presence
      of reduced maternal food consumption and reduced body weight gain. However,
      immune parameters, including histopathology, hematology, and antibody responses
      to sheep red blood cells (SRBC) in pups at 4 weeks of age were uncompromised. It
      is speculated that rather than the prenatal exposure protocol used here, the
      generation study design with both pre- and postnatal exposure may be preferable
      as a general screen to detect developmental immunotoxic injury after xenobiotic
      exposure.

PMID- 12007858
TI  - Immunotoxicity of nucleic acid reduced BioProtein--a bacterial derived single
      cell protein--in Wistar rats.
AB  - BioProtein is a single cell protein produced by a mixed methanotrophic and
      heterotrophic bacteria culture using natural gas as energy source, which has been
      approved for animal feed. BioProtein contains a large amount of nucleic acids
      making the product less suitable for human consumption, therefore, a nucleic acid
      reduced variant (NABP) has been developed by the manufacturer. The purpose of the
      present study was to establish the safety of NABP in a subchronic toxicity rat
      study. Groups of 10 male and 10 female Wistar rats were fed diets containing 0,
      6, 12 or 24% NABP for 13 weeks. Feeding NABP induced a humoral immune response
      and proliferation of phagocytic cell lines, mainly macrophages. The humoral
      response involved induction of NABP specific IgM and IgG. The proliferation of
      phagocytic cells involved increase of the white blood cell count of all dosed
      female groups. Males showed the same tendency, although, not statistically
      significant (P=0.09). The subsets of cells identified as neutrophils and
      eosinophils were increased and lymphocytes decreased. The histopathological
      examination revealed histiocytosis and accumulation of foamy macrophages in the
      mesenteric lymph nodes, hyperplasia of Kupffer cells in the liver, increased
      granulopoiesis in spleen and bone marrow, and infiltration of lamina propria of
      the large intestine with eosinophilic granulocytes. The most consistent and
      pronounced changes were observed in the highest dose group, but even at the
      lowest dose level some of the changes were present. Accordingly, a no-observed
      effect level could not be established based on this study.

PMID- 12007859
TI  - DDT inhibits the functional activation of murine macrophages and decreases
      resistance to infection by Mycobacterium microti.
AB  - DDT is still widely used in several parts of the world to control malaria,
      typhoid and dengue vectors, even though its use was banned in many countries
      based on toxicity data in wild life species. DDT has been shown to have
      immunotoxic effects in mice and to increase susceptibility to intracellular
      pathogens such as Mycobacterium leprae. However, little is known about the
      mechanisms underlying this effect. Activated macrophages play an important
      defensive role against intracellular pathogens, therefore our objective was to
      evaluate the effect of in vitro exposure to technical grade DDT (a mixture of
      three forms: 1,1,1-thricloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) (85%), o,p'
      DDT (15%) and o,o'-DDT (trace amounts)), p,p'-DDT, 1,1-dicloro-2,2-bis(p
      chlorophenyl)ethylene (p,p'-DDE) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane
      on the functional activation of J774A.1 macrophages and their capability to limit
      growth of intracellular pathogens, using Mycobacterium microti as a model. We
      evaluated cytotoxicity and the effect on cell proliferation of 2.5, 5.0 and 10
      microg/ml of DDT compounds. Functional macrophage activity (NO(*) and O(2)(-)
      production, and mRNA expression of TNF-alpha, IL-1beta and iNO synthase) and the
      ability of treated cells to limit infection by M. microti in IFN-gamma-activated
      macrophages were evaluated in cells exposed to 2.5 microg/ml of DDT compounds.
      Doses of 5 and 10 microg/ml induced direct cytotoxic effects precluding
      meaningful analysis of the above parameters, whereas 2.5 microg/ml of all DDT
      compounds inhibited macrophage activity and reduced their ability to limit the
      intracellular growth of M. microti without inducing cytotoxicity. Technical grade
      DDT and p,p'-DDE were the more potent compounds. Therefore, exposure to DDT
      compounds could represent an important risk for infection development by those
      intracellular pathogens against which NO(*) and/or O(2)(-) production represent
      the main immune protective mechanism.

PMID- 12007860
TI  - Evaluation of various serum and animal protein free media for the production of a
      veterinary rabies vaccine in BHK-21 cells.
AB  - We have carried out the adaptation of BHK-21 cells to two serum free (Ex Cell 520
      and HyQ PF CHO) and three animal protein free media: Ex Cell 302, HyQ PF CHO MPS
      and Rencyte BHK. After a direct switch or a gradual adaptation, we have achieved
      BHK-21 cells growth in the following media: HyQ PF CHO, HyQ PF CHO MPS, Rencyte
      BHK and Ex Cell 302. The most suitable media for BHK-21 cells growth, with
      respect to cell density and specific growth rate, were HyQ PF CHO and HyQ PF CHO
      MPS. Hence we have selected these media to study cell growth and the production
      of rabies virus. Kinetic studies of cell growth in spinner flasks using the
      selected media have shown that a maximal cell density of 2x10(6) cells x ml(-1)
      was reached in both media. For rabies virus production, the viral titer obtained
      was 1.7x10(6) FFU x ml(-1) in HyQ PF CHO as well as in HyQ PF CHO MPS medium. The
      optimization of rabies virus production by BHK-21 cells grown in a 2 l bioreactor
      using the selected media, pointed to the following parameters: culture mode,
      perfusion rate and multiplicity of infection (MOI), as being the critical factors
      for achieving a good virus yield. When tested in mice, the activity of the
      experimental vaccines prepared on HyQ PF CHO MPS medium has shown a protective
      activity that meets WHO requirements.

PMID- 12007861
TI  - The protection of hybridoma cells from apoptosis by caspase inhibition allows
      culture recovery when exposed to non-inducing conditions.
AB  - Programmed cell death (PCD) or apoptosis process in a hybridoma cell line induced
      by the deprivation of one of the main nutrients, glutamine, has been studied. The
      use of caspase inhibitors has enabled maintenance of cell viability during a
      significant period of time, when glutamine depletion was maintained in the
      culture. Two caspase inhibitors partially suppressed the progress of PCD under
      glutamine deprivation: Ac-DEVD-cho and z-VAD-fmk. Indeed, as a consequence of
      this protection, the number of viable cells decreased by 10% (for z-VAD-fmk) and
      by 80% (for Ac-DEVD-cmk) after 36 h of culture, while it decreased by 90% for a
      control culture in the absence of protective compounds. However, when the culture
      was exposed to non-apoptotic conditions after this period of time under apoptosis
      protection conditions, a normal growth pattern was not recovered. Interestingly,
      the simultaneous use of both inhibitors made the recovery of the cell culture
      possible even after a period of 36 h under glutamine depletion, indicating that
      the inhibition of the effector caspases occurs upstream of the point in which
      hybridoma cells enter into the commitment step of the death programme.

PMID- 12007862
TI  - A simple method for the detection of neurologic disorders associated with CAG
      repeat expansion using PCR-microtiter plate hybridization.
AB  - A new screening method was developed for the detection of CAG expanded alleles in
      patients with hereditary ataxia using polymerase chain reaction-based microtiter
      plate hybridization (PCR-MPH). The system can be applied to detect pathologic
      alleles by hybridization with the immobilized (CAG)48 repeat probe derived from
      the unrelated gene 'ERDA1' except for the CAG repeats. We examined 10 individuals
      with SCA3, 10 with Huntington disease and 30 normal controls (31 controls for
      SCA3) using this method. The results showed that a clear discrimination was
      possible in all cases. We suggest that this system be made available for mass
      screening of patients with hereditary ataxia disorders. This report is the first
      to demonstrate that a PCR-MPH system can be successfully applied to DNA size
      differentiation in addition to base pair mismatches. Also, our design of the
      probe is unique in that the probe motif stem from the unrelated gene sequence and
      not from the synthetic oligonucleotides.

PMID- 12007863
TI  - Influence of growth conditions on the production of a nisin-like bacteriocin by
      Lactococcus lactis subsp. lactis A164 isolated from kimchi.
AB  - The influence of growth parameters on the fermentative production of a nisin-like
      bacteriocin by Lactococcus lactis subsp. lactis A164 isolated from kimchi was
      studied. The bacteriocin production was greatly affected by carbon and nitrogen
      sources. Strain A164 produced at least 4-fold greater bacteriocin in M17 broth
      supplemented with lactose than other carbon sources. The amount of 3% yeast
      extract was found to be the optimal organic nitrogen source. While the maximum
      biomass was obtained at 37 degrees C, the optimal temperature for the bacteriocin
      production was 30 degrees C. The bacteriocin production was also affected by pH
      of the culture broth. The optimal pH for growth and bacteriocin production was
      6.0. Although the cell growth at pH 6.0 was nearly the same level at pH 5.5 and
      6.5, the greater bacteriocin activity was observed at pH 6.0. Exponential growth
      took place only during an initial period of the cultivation, and then linear
      growth was observed. Linear growth rates increased from 0.160 g(DCW) x l(-1) x h(
      1) to 0.245 g(DCW) x l(-1) x h(-1) with increases in lactose concentrations from
      0.5 to 3.0%. Maximum biomass was also increased from 1.88 g(DCW) x l(-1) to 4.29
      g(DCW) x l(-1). However, increase in lactose concentration did not prolong the
      active growth phase. After 20 h cultivation, cell growth stopped regardless of
      lactose concentration. Production of the bacteriocin showed primary metabolic
      kinetics. However, bacteriocin yield based on cell mass increased greatly during
      the late growth phase. A maximum activity of 131x10(3) AU x ml(-1) was obtained
      at early stationary growth phase (20 h) during the batch fermentation in M17L
      broth (3.0% lactose) at 30 degrees C and pH 6.0.

PMID- 12007864
TI  - Response of recombinant Chinese hamster ovary cells to hyperosmotic pressure:
      effect of Bcl-2 overexpression.
AB  - In an attempt to use the hyperosmotic pressure for improved foreign protein
      production in recombinant Chinese hamster ovary (rCHO) cells, the response of
      rCHO cells producing a humanized antibody (SH2-0.32-(Delta)bcl-2 cells) to
      hyperosmotic pressure was determined in regard to cell growth and death, and
      antibody production. Further, the feasibility of Bcl-2 overexpression in
      improving rCHO cell viability under hyperosmotic pressure was also determined by
      comparing control cells (SH2-0.32-(Delta)bcl-2) with Bcl-2 overexpressing cells
      (14C6-bcl-2). After 3 days of cultivation in the standard medium (294 mOsm x kg(
      1)), the spent medium was exchanged with the fresh media with various
      osmolalities (294-640 mOsm x kg(-1)). The results obtained show that hyperosmotic
      pressure inhibited cell growth in a dose-dependent manner, though 14C6-bcl-2
      cells were less susceptible to hyperosmotic pressure than SH2-0.32-(Delta)bcl-2
      cells. At 522 mOsm x kg(-1), SH2-0.32-(Delta)bcl-2 cells underwent a gradual cell
      death mainly through apoptosis due to the cytotoxic effect of hyperosmotic
      pressure. In contrast, Bcl-2 overexpression in 14C6-bcl-2 cells could delay the
      apoptosis induced by 522 mOsm x kg(-1) by inhibiting caspase-3 activation. Bcl-2
      overexpression could also improve the cellular membrane integrity of 14C6-bcl-2
      cells. When subjected to hyperosmotic pressure, the specific antibody
      productivity of SH2-0.32-(Delta)bcl-2 cells and 14C6-bcl-2 cells was increased in
      a similar extent. As a result, the final antibody concentration achieved in 14C6
      bcl-2 cells at 522 mOsm x kg(-1) was 2.5-fold higher than that at 294 mOsm x kg(
      1). At 580 mOsm x kg(-1), acute hyperosmotic pressure induced the rapid loss of
      viability in both SH2-0.32-(Delta)bcl-2 and 14C6-bcl-2 cells through necrosis
      rather than through apoptosis. Taken together, Bcl-2 overexpression and optimized
      hyperosmotic pressure could improve the antibody production of rCHO cells.

PMID- 12007865
TI  - Extraction of extracellular polymeric substances (EPS) of sludges.
AB  - The efficacies of extracting extracellular polymeric substances (EPS) from
      aerobic, acidogenic and methanogenic sludges using EDTA, cation exchange resin
      and formaldehyde under various conditions were compared. Results show that
      formaldehye plus NaOH was most effective in extracting EPS for all sludges; only
      1.1-1.2% of DNA in the sludge samples were detected, suggesting the EPS extracted
      were not contaminated by intracellular substances. For each gram of volatile
      solids, formaldehyde-NaOH extracted 165, 179 and 102 mg of EPS from aerobic,
      acidogenic and methanogenic sludges, respectively. All EPS were mainly composed
      of carbohydrate, protein and humic substance, plus small quantities of uronic
      acid and DNA. Carbohydrate was predominant in the acidogenic sludge (62% in the
      EPS extracted by formaldehyde-NaOH), whereas protein was predominant in the
      methanogenic sludge (41%). Humic substance, which has often been overlooked,
      accounted for 30.6, 8.4 and 22.8% of the extracted EPS from aerobic, acidogenic
      and methanogenic sludges, respectively. However, judging from EPS quantities
      estimated from confocal laser scanning microscopic observations, formaldehyde
      NaOH extracted only a limited portion of EPS. Optimization of extraction
      procedures and/or development of a more effective extraction method are
      warranted.

PMID- 12007866
TI  - Cellular surface display of dimeric Adx and whole cell P450-mediated steroid
      synthesis on E. coli.
AB  - Bovine adrenodoxin (Adx) was expressed on the surface of Escherichia coli as a
      monomeric fusion protein with the translocation unit of the AIDA-I
      autotransporter. The fusion protein remained anchored in the outer membrane by
      the beta-barrel of the autotransporter. Dimeric Adx molecules were formed
      spontaneously on the bacterial surface with high efficiencies. Adx dimers could
      be activated to biological function by chemical incorporation of the [2Fe-2S]
      cluster. By adding purified adrenodoxin reductase and P450 CYP11A1, a whole cell
      biocatalyst system was obtained, which effectively synthesized pregnenolone from
      cholesterol. Addition of artificial membrane constituents or detergents, which
      was indispensable before to get functional steroidal P450 enzymes, was not
      necessary. The whole cell activity (0.21 nmol x h(-1) x nmol(-1) CYP11A1) was in
      the same range as obtained earlier for reconstitution assays. The whole cell
      system developed here is an easy to handle, stable tool for the expression of
      membrane-associated P450 enzymes without the need of microsome preparation or
      reconstitution of artificial membrane vesicles. Moreover, it is the first report
      on functional dimer formation of a protein anchored on the surface of E. coli
      after being transported as a monomer. This seems to be a special feature of the
      autotransporter translocation unit, containing a beta-barrel, motile in the outer
      membrane and opens a new dimension for the surface display of multimeric
      proteins.

PMID- 12007867
TI  - Non-polar distribution of green fluorescent protein on the surface of Autographa
      californica nucleopolyhedrovirus using a heterologous membrane anchor.
AB  - Heterogeneous proteins can be displayed on the surface of the budded form of
      Autographa californica nucleopolyhedrovirus (AcMNPV) after fusion of the display
      protein to the AcMNPV major envelope glycoprotein, gp64. However, display is
      restricted to the poles of the virion and is relatively low level. To investigate
      the use of alternative membrane anchor sequences that would be compatible with
      virus surface display, we have constructed a display vector containing the gp64
      signal peptide and a membrane anchor from the vesicular stomatitis virus (VSV) G
      glycoprotein. Introduction of a gene encoding green fluorescent protein (GFP)
      between these signals led to abundant display of GFP on the surface of insect
      cells and on recombinant budded virions. In addition, and in contrast to gp64
      based fusion proteins, GFP was localized to the lateral virion surfaces.

PMID- 12007868
TI  - Recombinant Interleukin-2 (rIL-2), aldesleukin.

PMID- 12007869
TI  - In vitro effect of copper ions on transbilayer distribution of aminophospholipids
      in synaptosomal membrane of walleye pollock (Theragra chalcogramma).
AB  - Effect of copper ions on lipid matrix organization of synaptosomal membrane of
      the marine fish Theragra chalcogramma was investigated. It was demonstrated that
      interaction of copper ions with these membrane stimulated the process of lipid
      peroxidation and caused changes in the transbilayer distribution of
      aminophospholipids. Accessibility of phosphatidylethanolamine was increased more
      than twice, and of phosphatidylserine more than ten times, that can be explained
      by changes in asymmetrical structure of lipid matrix of synaptosomal membrane. We
      suggested, that the main mechanism of copper-stimulated damage in transbilayer
      organization of the membrane is oxidation of membrane protein sulfhydryl groups.

PMID- 12007870
TI  - The influence of sediment and feeding on the elimination of polycyclic aromatic
      hydrocarbons in the freshwater amphipod, Diporeia spp.
AB  - The elimination of non-polar organic contaminants from sediment dwelling aquatic
      invertebrates was thought to be dominated by fecal elimination. This was
      particularly thought to be the case for the amphipod, Diporeia spp. that
      encapsulates the fecal material in a peritrophic membrane. The elimination of
      selected PAH congeners by Diporeia spp. was determined in the presence of three
      solid substrates and under water only conditions. The elimination was generally
      enhanced by the presence of a solid substrate whether or not the organism
      employed the material as a food source. The greater the sorptive capacity of the
      substrate, the greater its influence on the elimination process. Elimination via
      the fecal route was generally insignificant except for the elimination of BaP in
      the presence of sediment. In this case, the fecal elimination accounted for up to
      40% of the total elimination, and the extent of elimination via the fecal route
      increased with the amount of fecal material produced. Thus, it is clear from the
      above effort that the main mechanism for elimination of contaminants in the
      presence of a substrate is primarily via passive diffusion from the organism with
      subsequent sorption to the solid substrate, which maintains the chemical activity
      gradient between the organism and the water. This effort refutes the earlier
      hypothesis that fecal elimination is the dominant route of elimination for
      Diporeia spp., and that the peritrophic membrane plays any substantial role in
      the elimination process.

PMID- 12007871
TI  - An in vitro vitellogenin bioassay for oestrogenic substances in the medaka
      (Oryzias latipes).
AB  - We developed an in vitro bioassay for oestrogenic compounds based on vitellogenin
      as a biomarker. To quantify the induction of vitellogenin in medaka (Oryzias
      latipes) we established a sandwich enzyme-linked immunosorbent assay (ELISA).
      This ELISA was carried out with two different monoclonal antibodies specific for
      the yolk precursor protein vitellogenin and the high molecular weight yolk
      proteins (lipovitellin) of medaka. Purified lipovitellin of medaka was used as a
      standard for the ELISA and could be quantified down to a concentration of 9
      ng/ml. The calibration curve was linear up to at least 600 ng/ml and the intra
      assay coefficient of variance was 3.2%. The application of the sandwich ELISA was
      tested using blood samples of males and females as well as primary hepatocyte
      cultures of medaka. Vitellogenin synthesis in cultured liver cells of males was
      induced by 1 and 100 nM of the xenoestrogen 17alpha-ethynylestradiol (EE(2)). The
      first production of vitellogenin was detected 6 days after hormone application.
      In contrast, isolated liver cells of sexually mature females, which were treated
      in the same manner, showed vitellogenin expression from the beginning of
      cultivation and its synthesis increased and remained high at 100 nM EE(2).
      However, the induction of vitellogenin synthesis in male hepatocytes in vitro
      could be maintained for at least one month and this indicated viable and
      differentiated liver cells. The hepatocyte cultures of male medaka in combination
      with the sandwich ELISA were shown to be a suitable tool to detect and quantify
      oestrogenic activity of chemicals.

PMID- 12007872
TI  - The effects of long-term cadmium exposure on the growth and survival of juvenile
      bull trout (Salvelinus confluentus).
AB  - Bull trout (Salvelinus confluentus) have been listed recently as threatened in
      the United States under the federal Endangered Species Act. This species
      currently resides, or historically resided, in several waterways that either are
      impacted or are under threat of impact from metals mining activities. We
      conducted a 55-day sub-chronic (i.e. sublethal) cadmium (Cd) exposure in water at
      30 mg l(-1) (as CaCO(3)) hardness, pH 7.5, and 8 degrees C. Exposures were
      conducted using six replicate exposure tanks for each of the six treatments (five
      Cd concentrations and one control). Measured Cd concentrations were <0.013
      (control), 0.052, 0.089, 0.197, 0.383, and 0.786 microg Cd l(-1). Exposure to
      0.786 microg Cd l(-1) caused increased mortality (37%) and reduced growth (28%
      reduction in weight change) in fish exposed for 55 days. All Cd exposure
      concentrations caused significant whole body accumulation of Cd compared with
      controls. Our results indicate that even though fish are significantly
      accumulating Cd in each non-control treatment, growth reductions in bull trout
      occurred only at Cd concentrations that also caused significant mortality. The Cd
      concentration that reduced growth and survival in this long-term exposure (0.786
      microg Cd l(-1)) is greater than the recently-revised US federal aquatic life
      criteria (ALC) value for the corresponding hardness concentration (ALC=0.62
      microg Cd l(-1) for acute effects and 0.11 microg Cd l(-1) for chronic effects).

PMID- 12007873
TI  - Relationship between exposure duration, tissue residues, growth, and mortality in
      rainbow trout (Oncorhynchus mykiss) juveniles sub-chronically exposed to copper.
AB  - We conducted a 56-day sub-chronic test on the effects of Cu on rainbow trout
      (Oncorhynchus mykiss) fry at a nominal water hardness of 100 mg l(-1) (as
      CaCO(3)). Response measures were growth, whole body Cu concentrations, and
      mortality. Significant mortality was observed in fish exposed to 54.1 microg Cu
      l(-1) (47.8%) and 35.7 microg Cu l(-1) (11.7%). Growth was dose-dependent over
      the range of Cu treatments (0-54 microg Cu l(-1)), and was modeled as a function
      of Cu exposure concentration and exposure duration. Calculated inhibition
      concentrations (based on change in wet weight through a 56-day Cu exposure) were
      IC(50)=54.0 microg Cu l(-1), IC(20)=21.6 microg Cu l(-1), IC(10)=10.8 microg Cu
      l(-1), and IC(01)=1.1 microg Cu l(-1). Measured whole body Cu was also dose
      dependent, and growth of trout fry was readily modeled as a function of tissue Cu
      and exposure duration. This model was virtually identical to a model previously
      developed for rainbow trout exposed to Cu at a hardness of 25 mg l(-1). Following
      the 56-day exposure period, we performed a 96-h acute challenge to Cu and Cd to
      evaluate the effects of Cu acclimation on acute Cu and Cd toxicity. Sensitivity
      to Cu was dependent on the 'acclimation dose'; trout previously held in control
      aquaria (i.e. not acclimated to Cu) suffered over 80% mortality, whereas trout
      previously exposed to 35.7 microg Cu l(-1) for 56 day suffered 20% mortality.
      These fish also showed somewhat reduced sensitivity to Cd, suggesting acclimation
      to Cu can enhance tolerance to other metals. Finally, the relationship between
      growth response and hardness (derived from several studies) appeared to have a
      different slope than the hardness relationship previously observed for lethality
      responses.

PMID- 12007874
TI  - Phagocytic activity of marine and freshwater bivalves: in vitro exposure of
      hemocytes to metals (Ag, Cd, Hg and Zn).
AB  - We measured non-specific immune function of various bivalves from marine
      (Cyrtodaria siliqua, Mactromeris polynyma, Mesosdesma arctatum, Mya arenaria, Mya
      truncata, Mytilus edulis, Serripes groenlandicus, Siliqua costata) and freshwater
      environments (Dreissena polymorpha and Elliptio complanata). We used flow
      cytometry to quantify the phagocytosis of fluorescent microspheres by hemocytes
      exposed in vitro to increasing levels of various metal compounds (AgNO(3),
      CdCl(2), CH(3)HgCl, HgCl(2) and ZnCl(2)). In some species, low doses of mercury
      (organic and inorganic) and Zn suggest a hormesis-like stimulation of phagocytic
      activity. At higher levels of exposure, all metals tested induced a significant
      dose-related inhibition of hemocyte phagocytosis. The species-specific
      sensitivity of the assay was determined by comparing the in vitro exposure using
      the metal concentration inducing a 50% suppression (EC(50)) of the phagocytic
      activity. Different species expressed different levels of sensitivity. Our
      results show the variability of the toxic response of different species within a
      group of similar organisms. It also highlights the need to consider species
      species differences in ecotoxicological risk assessment.

PMID- 12007875
TI  - Relationships among the cell cycle, cell proliferation, and aryl hydrocarbon
      receptor expression in PLHC-1 cells.
AB  - Aryl hydrocarbon receptor (AHR) ligands such as 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) cause altered cell proliferation in many tissues in vivo and cell
      types in vitro, and the AHR has been suggested to play a role in cell cycle
      regulation in mammalian systems. However, the mechanisms underlying these effects
      are poorly understood. The overall objective of the present work was to
      investigate possible interactions between cell proliferation, the cell cycle, and
      AHR signal transduction in a piscine system, the PLHC-1 cell line, which is being
      used increasingly in aquatic toxicological research. The specific objectives were
      to characterize proliferation rates and the cell cycle in these cells, to measure
      effects of TCDD on cell proliferation, and to determine if expression of the AHR
      varies during the cell cycle. The doubling time of PLHC-1 cells was determined to
      be 22 h, and the durations of the G1, S and G2/M stages of the cell cycle were
      13, 3, and 6 h, respectively. A minimum seeding density of 1.2 x 10(5)
      cells/cm(2) in medium with 10% calf serum and 0.3 x 10(5) cells/cm(2) in 10%
      fetal bovine serum was found to be required for subsequent proliferation. Of
      several cell cycle inhibitors tested, only aphidicolin and nocodazole were
      effective for obtaining synchronous cell populations. TCDD was found to inhibit
      PLHC-1 cell proliferation in a time- and dose-dependent manner in multiple
      passages of one sub-clone, but not in several other sub-clones. Neither AHR mRNA
      nor protein expression varied during the cell cycle, as measured by RT-PCR and
      specific binding of [(3)H]TCDD in synchronous PLHC-1 cells. This work establishes
      techniques for identifying and characterizing possible interactions between the
      cell cycle and AHR signal transduction in PLHC-1 cells. Taken together, the
      results indicate that PLHC-1 cells are amenable to analysis of AHR-cell cycle
      interactions, but that heterogeneity of sub-clones may complicate their use for
      investigating AHR-mediated changes in proliferation.

PMID- 12007876
TI  - Bioavailability of waterborne strontium to the common carp, Cyprinus carpio, in
      complexing environments.
AB  - The uptake of strontium (Sr) and calcium (Ca) in the common carp, Cyprinus
      carpio, was studied in chemically defined freshwater in the presence of the
      complexing ligands, ethylenediaminetetraacetic acid (EDTA), and nitrilotriacetic
      acid (NTA). The uptake rates were measured in the whole body, gills, and blood of
      the fish after an exposure period of 3 h. The uptake rates were determined by
      using the radiotracers (85)Sr and (45)Ca, and analyzed as a function of the free
      ion activity of Sr and Ca in water. Although Sr(2+) activity decreased, the
      uptake of Sr showed an increase at relatively low concentrations of EDTA and NTA,
      and a decrease at relatively high concentrations. This can be explained by the
      decreased competition between Sr(2+) and Ca(2+) at the gill uptake sites due to
      approximately 30-140-fold higher affinity of EDTA and NTA for Ca(2+) than Sr(2+).
      With decreasing Ca(2+) activity, Ca uptake rates decreased in the presence of
      EDTA and NTA, but the effect of NTA was less pronounced. A Michaelis-Menten type
      competitive inhibition model was derived that could predict the whole-body Sr and
      Ca uptake rates, taking into account the ambient Sr(2+) and Ca(2+) activities in
      the presence of EDTA. In case of NTA, the uptake rates were found to be 1.5-3.2
      times higher than what was predicted by the model. When the fish were exposed to
      complexing environments in the complete absence of Ca, an increased uptake of Sr
      was still observed in case of NTA, but not EDTA. The increased uptake in the
      presence of NTA is attributed to the direct uptake of SrNTA(-) and CaNTA(-)
      complexes from water. The results reveal that the uptake of Sr and Ca in carp is
      not merely a function of the free metal-ion activity but that certain complex
      species may contribute significantly to overall uptake.

PMID- 12007877
TI  - Toxicology of dietary nickel in lake whitefish (Coregonus clupeaformis).
AB  - The sublethal toxicity associated with exposure of adult lake whitefish
      (Coregonus clupeaformis) to diets containing 0, 10, 100, and 1000 microg Ni per g
      for 10, 31, and 104 days was assessed through the measurement of responses,
      through a range of levels of biological organization. The accumulation and
      distribution of Ni in these fish are described in the previous manuscript
      (Ptashynski and Klaverkamp, 2001. Aquat. Toxicol. in press). Hematological
      parameters, including concentrations of glucose and hemoglobin and hematocrit,
      were not different between control and treated fish. Organ and whole organism
      parameters, including LSI, growth, and condition factor, were also unaffected.
      Histopathological lesions in kidney and liver proved to be the most sensitive and
      reliable indicators of Ni exposure. In livers of treated fish, areas of focal
      necrosis and altered bile ducts were observed. Histological alterations were
      observed throughout the posterior kidneys, in glomeruli, tubules, collecting
      ducts, and hematopoietic tissue, in fish fed medium and high dose diets. In
      whitefish kidneys, the frequency (%) of altered distal tubules and fields of
      views with alterations increased with the dose and duration of exposure.
      Significant increases in metallothionein concentrations were observed in
      intestine of whitefish fed the high dose diet on day 10, but these increases were
      not sustained. Significant increases in lipid peroxide concentrations were also
      observed in plasma of whitefish fed the high dose diet on day 31, but were not
      observed on day 104. These biochemical responses to dietary Ni require further
      evaluation. To evaluate exposure of natural populations of fish to Ni, analysis
      of Ni in kidney and liver and assessment of renal and hepatic histopathology are
      recommended for use in field bio-monitoring programs.

PMID- 12007878
TI  - Accumulation and distribution of dietary nickel in lake whitefish (Coregonus
      clupeaformis).
AB  - Benthic-feeding fish residing in Ni-contaminated systems are exposed to Ni
      through ingestion of contaminated food items and sediments. Lake whitefish
      (Coregonus clupeaformis) were fed diets at a ration of 0.5% of body weight three
      times a week containing 0, 10, 100, and 1000 microg Ni/g (as NiSO(4)) for 10, 31,
      and 104 days. Stomach, pyloric caeca, intestine, kidney, liver, gall bladder,
      gonad, gill, bone, muscle, skin, and scales were analyzed to evaluate the
      accumulation and distribution of Ni. Fish fed the medium and high dose diets
      accumulated significant amounts of Ni in a majority of the tissues sampled, even
      after only 10 days of exposure. Ni concentrations were highest in intestine and
      pyloric caeca of whitefish fed 1000 microg Ni/g on day 10, but decreased on
      subsequent sampling days, possibly due to protective mechanisms. Ni accumulation
      in stomach, kidney, liver, gill, skin, and scales was dose and duration
      dependent. Ni concentrations measured in bone, gall bladder, gonad, and muscle of
      fish fed the control diet for 10 days and fish fed the high dose diet for all
      durations appeared to increase in a duration-dependent manner. Exposure to Ni
      altered the concentrations of Cu and Zn in tissues of lake whitefish. However, Cu
      and Zn concentrations in the tissues analyzed were variable and did not follow a
      common pattern or trend. The tissues that best assess dietary Ni bioavailability
      are kidney and scales. The toxicology of Ni in these fish is described in the
      next manuscript (Aquat. Toxicol., in press (b)).

PMID- 12007879
TI  - Chemokines in health and disease.
AB  - Chemokines belong to a large family of structurally related proteins that play a
      pivotal role in immune system development and deployment. While a large number of
      chemokines (approximately 50) and their receptors (approximately 20) have been
      identified from humans or mice, only a few are known in domestic veterinary
      species. Recent data implicate CXCL8 (old name, IL-8), CXCL10 (old name, IP-10)
      (both CXC chemokines) and CCL2 (old name, MCP-1) (a CC chemokine) in veterinary
      infections, inflammatory diseases or reproduction. There is compelling evidence
      for neutrophil targeting chemokines such as CXCL8, in ovine bacterial mastitis,
      bovine pneumonic pasturellosis and equine chronic obstructive pulmonary disease
      (COPD). Monocyte and lymphocyte targeting chemokines appear to play a role in
      caprine arthritis encephalitis (CCL2) and canine endotoxemia (CXCL10).
      Interestingly CCL2 is considered a missing link between hormonal and cellular
      control of luteolysis. On the other hand, canine cardiovascular conditions are
      associated with overexpression of CCL2 and CXCL8. Furthermore, a number of
      veterinary viral pathogens encode chemokine/chemokine receptor like molecules or
      chemokine binding proteins that may help viruses to evade the immune system.
      Here, we provide an overview of the chemokine system and critically evaluate the
      current literature implicating chemokines in veterinary pathophysiology.
      Furthermore, we highlight promising areas for further research and discuss how
      and why chemokine antagonists are viewed as next generation anti-inflammatory
      drugs for the 21st century.

PMID- 12007880
TI  - Recruitment of intestinal CD45RA+ and CD45RC+ cells induced by a candidate oral
      vaccine against porcine post-weaning colibacillosis.
AB  - To assess the influence of a live attenuated oral vaccine against porcine post
      weaning colibacillosis (PWC) induced by enterotoxigenic Escherichia coli (ETEC)
      on mucosal lymphoid cell CD45 isoforms expression, experimental group of weaned
      pigs (n=6) was immunized orally with F4ac+ non-ETEC strain (day 0) and challenged
      with F4ac+ ETEC strain 7 days latter. Non-immunized ETEC-infected pigs (n=6)
      served as control. All pigs were killed on post-challenge day 7. The small
      intestine was excised for isolation of jejunal lamina propria (JLP) and ileal
      Peyer's patch (IPP) lymphocytes and immunohistochemical studies. The results
      obtained by immunophenotyping of isolated cells show that the proportion of
      CD45RA+ and CD45RC+ JLP, but not IPP, cells were higher in the non-ETEC-immunized
      ETEC-infected pigs versus non-immunized infected. Additionally, while CD45RA+ JLP
      cells increased only slightly, the expression of CD45RC isoform on the JLP cells
      was significantly higher (P< or =0.01) in the experimental than in the control
      group. The results of the quantitative phenotypic analysis of isolated
      lymphocytes were not confirmed by immunohistochemical in situ staining. The
      majority of intestinal immune cells was found to express CD45RA antigen in situ,
      but no differences were observed between the two groups of weaned pigs neither in
      CD45RA+ nor in CD45RC+ cells. Our overall evidence indicates that the increased
      expression of CD45RC isoform was in fact induced in a limited number of JLP T
      cells in the vaccinated pigs. This was accompanied with the impaired protection
      of the vaccinated pigs from challenge-induced PWC.

PMID- 12007881
TI  - Bluetongue virus-induced activation of primary bovine lung microvascular
      endothelial cells.
AB  - Bluetongue is an insect-transmitted viral disease of sheep and some species of
      wild ruminants. Infection of lung microvascular endothelial cells (ECs) is
      central to the pathogenesis of bluetongue virus (BTV) infection of ruminants, but
      it is uncertain as to why cattle are resistant to BTV-induced microvascular
      injury and bluetongue disease. Thus, in order to better understand the
      pathogenesis of BTV infection of cattle, mRNAs encoding a variety of inflammatory
      mediators were quantitated by real-time polymerase chain reaction in primary
      bovine lung microvascular ECs (BLmVECs) exposed to BTV and/or EC-derived
      mediators. BTV infection of BLmVECs significantly increased the transcription of
      genes encoding interleukin-1 (IL-1), IL-6, IL-8, cyclooxygenase-2, and inducible
      nitric oxide synthase. Treatment of BLmVECs with EC-lysates that contained BTV as
      well as cytokines increased both the incidence of apoptosis and expression of
      cellular adhesion molecules, as compared to infection of BLmVECs with BTV alone.
      Thus, BTV infection caused activation of BLmVECs with production of inflammatory
      mediators that alter the mechanism of cell death of BLmVECs and exert potentially
      potent effects on blood coagulation. The activities of BTV-induced-EC-derived
      inflammatory mediators likely contribute to the resistance of cattle to BTV
      induced microvascular injury and bluetongue disease.

PMID- 12007882
TI  - Altered expression of cellular genes in neutrophils of periparturient dairy cows.
AB  - The periparturient dairy cow undergoes a plethora of physiological changes,
      including changes in the immune system that lead to profound effects on animal
      health. Of the immune cells affected at parturition, the neutrophil has been of
      particular interest due to its primary role in innate immune defense against
      mastitis. Immune functions of bovine neutrophils are known to be depressed around
      parturition, but it has not been discerned at what level these alterations occur,
      including the possibility that parturition induces changes in expression of key
      genes. The hypothesis of the present study was that blood neutrophils respond to
      the physiology of parturition by altering the expression of genes needed for
      normal cellular functions. The main objectives of the study were to detect and
      characterize parturition induced changes in neutrophil gene expression, to
      determine if altered gene expression was significantly associated with the main
      steroid hormones of bovine parturition, and to obtain putative identities of
      differentially expressed neutrophil genes. Differential gene expression was
      detected and characterized through mRNA abundance changes in neutrophils, and
      steroid hormone concentrations by RIA assay of periparturient serum samples.
      Preliminary assessment of differential gene expression was done using
      differential display reverse transcription polymerase chain reaction (DDRT-PCR)
      followed by secondary screening using high throughput cDNA dot blot
      hybridization. Altered gene expression was confirmed using Northern blot
      hybridization and detailed expression patterns characterized using quantitative
      slot blot analysis. The identities of two fully characterized transcripts with
      clear parturition induced repression (P< or =0.02) in neutrophils had high DNA
      sequence homology with genes that encode bovine mitochondrial cytochrome b (cytb)
      and rig/ribosomal protein S15 (rig/RPS15). These proteins are critical for normal
      respiratory metabolism and translation in cells, respectively. The gene
      expression profiles for cytb were significantly related to serum progesterone
      concentration (r=0.44) and for rig/RPS15 to progesterone and estradiol
      concentrations (r=0.35, 0.36, respectively). Eleven additional transcripts showed
      evidence of parturition induced repression in neutrophils and were putatively
      identified as representing genes of the citric acid cycle and various DNA binding
      proteins. Results of this study show for the first time that genes regulating
      basic life functions of bovine neutrophils may be repressed by parturition,
      possibly due to influences of steroid hormones.

PMID- 12007883
TI  - Effect of transcutaneous immunization with co-administered antigen and cholera
      toxin on systemic and mucosal antibody responses in sheep.
AB  - Direct application of antigens to skin together with an adjuvant, a procedure
      called transcutaneous immunization (TCI), can induce systemic immune responses in
      mice, humans, cats and dogs. In previous studies we found that cholera toxin (CT)
      applied topically on unbroken skin induces systemic antibody and lymphocyte
      proliferative responses in sheep. The current study examined whether concurrent
      administration of CT and tetanus toxoid (TT) delivered transcutaneously could
      induce specific antibody responses to both antigens in sheep. Antibodies to both
      TT and CT were induced by TCI although antibody titres in serum to TT were higher
      in sheep receiving TT plus alum by intramuscular injection (n=5) than TT plus CT
      by TCI (n=5). The ratio of IgG1/IgG2 antibody to TT in serum was near unity, and
      the route of immunization, TCI versus injection, did not influence this ratio. In
      contrast, the ratio of IgG1/IgG2 antibody differed significantly between the two
      antigens, TT and CT, delivered by TCI, with a higher proportion of IgG1 antibody
      in serum to CT than TT. Antibody to TT was detected in lung washes from TCI and
      injection groups, with IgG1 predominating over IgG2 in both groups. IgA
      antibodies to CT and TT were detected in sera of CT and TT-immunized groups
      respectively but in lung washes IgA antibody to TT was detected only in the
      injection group. Results show that TCI induced systemic antibody responses to CT
      and the co-administered antigen TT, whereas no evidence was obtained for mucosal
      IgA responses following TCI.

PMID- 12007884
TI  - Functions of neutrophils in sheep experimentally infected with Ehrlichia
      phagocytophila.
AB  - Ehrlichia phagocytophila infection in sheep is characterized by persistent
      neutropaenia, indicative of decreased phagocytic capacity. This predisposes
      infected animals to other infections. A whole blood flow cytometrical method was
      used to document the degree and extent of reduced phagocytic and respiratory
      burst activity in phagocytes during an experimental infection with E.
      phagocytophila, and monitored until 56 days post-infection. Six sheep at 5 months
      of age were inoculated with an intravenous injection of infected blood. Six age
      matched sheep were used as controls. A period of reduced respiratory burst
      lasting up to Day 17 post-infection was recorded. The population of cells showing
      phagocytic activity without respiratory burst was larger in the infected animals
      compared to controls up to Day 45 post-infection.

PMID- 12007885
TI  - Effects of prenatal stress on cellular and humoral immune responses in neonatal
      pigs.
AB  - In the present study, we investigated the effects of a daily 5 min restraint
      stress of pregnant sows in the last five gestational weeks on the development and
      reactivity of the immune system of the offspring. Maternal stress resulted in
      significant decreased serum immunoglobulin G (IgG) concentrations in suckling
      piglets at 1 and 3 days of age. Furthermore, the stress treatment of the sows had
      an immunosuppressive effect on lymphocyte proliferation in response to the T-cell
      mitogen concanavalin A (ConA) at postnatal days 1 and 7. A suppressive effect was
      also found in response to the B-cell mitogens lipopolysaccharid (LPS) at days 1
      and 35 and pokeweed mitogen (PWM) at day 1 of life, whereas natural killer (NK)
      cell cytotoxicity was not altered by prenatal stress. The relative thymus weights
      were significantly reduced in prenatally stressed piglets on the first and 35th
      day of life and the morbidity and mortality during the suckling period were
      significantly increased in prenatally stressed litters, as shown by a higher
      frequency of diseased and died piglets per litter. In addition, the ConA-, LPS-
      and PWM-stimulated lymphocyte proliferation at the age of 7, 21 and 35 days, and
      the NK cell cytotoxicity at the age of 21 and 35 days decreased in prenatally
      stressed and in control piglets 1h after a corticotropin (ACTH) injection.
      However, the cellular immunity was always higher in the control piglets which
      might be a result of the weaker stress hormone reactivity in prenatally stressed
      animals. In conclusion, the results provide first experimental evidence that
      prenatal maternal stress during late gestation is able to impair both humoral and
      cellular immune function in suckling piglets. The data also suggest that
      gestational stress in pigs may affect the ontogeny of the foetal immune system
      with consequences on the susceptibility to diseases and immune responsiveness to
      stressful stimuli of the offspring.

PMID- 12007886
TI  - Evaluation of Th1, Th2 and immunosuppressive cytokine mRNA expression within the
      colonic mucosa of dogs with idiopathic lymphocytic-plasmacytic colitis.
AB  - The objective of this study was to evaluate the expression of the
      immunoregulatory and pro-inflammatory cytokines interleukin (IL)-2, IL-4, IL-6,
      IL-12p35, IL-12p40, interferon-gamma (IFN-gamma), and tumour necrosis factor
      alpha (TNF-alpha), and the expression of the predominantly immunosuppressive
      cytokines transforming growth factor-beta (TGF-beta) and IL-10 in canine
      idiopathic lymphocytic-plasmacytic colitis (LPC). Semi-quantitative reverse
      transcriptase-polymerase chain reactions were performed using specific primers on
      RNA isolated from the colonic mucosa of healthy dogs, dogs with clinical signs of
      large intestinal disease but normal histopathology of the colon, and dogs with
      LPC. Canine LPC was associated with over-expression of IL-2 compared to healthy
      colonic mucosa (p<0.01) and the mucosa of dogs with large intestinal diarrhoea
      but normal histopathology (p<0.05). Higher levels of TNF-alpha mRNA were also
      seen in LPC compared to healthy mucosa (p<0.05). These results indicate that LPC
      is associated with activation of CD4+ T-helper lymphocytes and increased
      production of T-helper-1-type cytokines.

PMID- 12007887
TI  - Cellular and molecular characterisation of the ovine rectal mucosal environment.
AB  - Immunohistological characterisation of ovine rectal tissue has revealed the
      presence of lymphoid follicles, predominantly in the submucosa, that closely
      resemble those found in intestinal Peyer's patches (PPs). Distinct T (CD4+, CD8+,
      gammadelta-TCR+) and B (CD21+, CD45R+) lymphocyte staining patterns were observed
      within and around follicles of the rectal mucosa. In addition, IgA+ and IgE+
      cells were also found at this tissue site, with both phenotypes commonly residing
      in the lamina propria. RT-PCR examination of the cytokines expressed in the
      rectal mucosal tissue revealed consistently high levels of TGFbeta and IL-8 mRNA,
      low levels of IL-2 mRNA and no detectable IL-4 mRNA. The presence of lymphoid
      follicles, IgA+ plasma cells and IgA-inducing cytokines in rectal tissue of sheep
      indicate that this may be a suitable route for delivering mucosal vaccines.

PMID- 12007888
TI  - Blood lymphocyte subsets in pigs vaccinated and challenged with Actinobacillus
      pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae bacterins do not induce protection in pigs while
      infection with low doses of the CM5 strain of A. pleuropneumoniae given by
      aerosol induces complete protection. To evaluate possible correlates of
      protection in blood lymphocyte subset phenotypes, pigs were treated with a
      commercial bacterin given intramuscularly, low dose (10(5)cfu/ml) aerosol
      infection with CM5 or control treatments of the bacterin adjuvant or phosphate
      buffered saline. All pigs were challenged with a high dose (10(7)cfu/ml) of A.
      pleuropneumoniae. Lymphocytes and sera were collected prior to and following
      primary and secondary immunizations and challenge, for evaluation of B- and T
      cell markers and antibody to four A. pleuropneumoniae antigens. IgM(micro)+ B
      cells were increased following primary exposure to antigen in the bacterin
      vaccinated group only. An increase in CD4+ cells in the LD aerosol-infected group
      was apparent following secondary exposure to antigen. These early changes suggest
      little difference in lymphocyte populations between treatment groups, however,
      greater differences were observed following high-dose challenge; CD4+ lymphocytes
      were increased significantly in both bacterin and LD-challenged groups (p<0.05)
      while CD8+ cells decreased in the LD-group at this time period. Consequently,
      there were significant differences (p<0.05) in the CD4:CD8 ratio after high-dose
      challenge compared to earlier time points and control groups. Variation in
      cellular expression of SLA-DR and DQ was observed but trends correlating to
      treatment group were not evident. Complete protection or lack of protection
      associated with LD challenge or immunisation resulted in significant differences
      in B-cell frequencies and CD4:CD8 ratio phenotypes in pigs, but only changes in
      CD4:CD8 ratios appeared relevant to protection.

PMID- 12007889
TI  - Bioinformatics and high throughput approach to create genomic resources for the
      study of bovine immunobiology.
AB  - The advent of technologies such as real-time reverse transcriptase polymerase
      chain reaction (RT-PCR) and cDNA microarrays herald a new era in the study of
      biological systems. In immunobiology, these advances have begun to impact studies
      of infectious diseases, inflammatory processes, and immune cell function.
      However, a lack of genetic reagents for domestic and companion animals has
      precluded widespread application of new technologies to studies in these systems.
      We have recently described development of cDNA microarrays for studying bovine
      immunobiology. Although powerful in revealing genes involved in immunological
      phenomena in cattle, these resources were limited by a lack of genes known to
      function in immune responses from other species, such as mouse and human. To
      address this shortcoming, we used a combination of bioinformatics and high
      throughput RT-PCR to create amplicons representing over 270 bovine genes whose
      orthologs in other species were known to function in immune responses. Amplified
      gene segments were prepared from cDNA representing RNA isolated from either
      unstimulated or concanavalin A (ConA) stimulated peripheral blood mononuclear
      cells (PBMCs). In total, 276 genes were amplified from cDNA representing
      unstimulated bovine PBMC RNA or from cDNA representing ConA stimulated bovine
      PBMC RNA. A web-accessible resource (http://gowhite.ans.msu.edu/public_php/gd
      bovine-immunology.php) has been created to assist in dissemination of this novel
      resource. The web-accessible resource contains information on gene name, the
      forward and reverse primers used to amplify each segment, expected product size,
      and if the gene was found in unstimulated PBMCs or only in ConA stimulated PBMCs.
      Gene names appear as hyperlinks to the Genbank pages representing the bovine gene
      or expressed sequence tag (EST) used to generate each primer pair.

PMID- 12007890
TI  - Lack of MHC expression and retention of ultrastructural characteristics by
      xenograft transmissible venereal tumor cells in SCID mice.
AB  - Canine transmissible venereal tumor (CTVT) is primarily a tumor of adult dogs
      with a high incidence of spontaneous regression. We recently reported a xenograft
      model of CTVT (XTVT) in NOD/SCID mice. XTVT cells retain cytological and
      histological features of CTVT as well as characteristic rearranged LINE/c-MYC
      junction [Am. J. Vet. Res. 62 (2001) 907]. In this paper, we demonstrate that
      XTVT cells maintain ultrastructural characteristics of CTVT and do not express
      MHC classes I and II molecules.

PMID- 12007891
TI  - Development of a baculovirus expression system for soluble porcine tumor necrosis
      factor receptor type I and soluble porcine tumor necrosis factor receptor type I
      IgG fusion protein.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of inflammatory
      responses and gram-negative bacterial sepsis, but the role that it plays during
      Salmonella enterica species bacterial infections in swine has not yet been
      elucidated. To facilitate studies on the role of TNF-alpha on the pathology
      associated with Salmonella infections in pigs, recombinant soluble porcine TNF
      receptor type I (rspTNF-RI) and soluble TNF receptor type I fused to the Fc
      region of porcine IgG1 (rspTNF-RI-IgG) were expressed in insect cells using a
      baculovirus expression system. The proteins were secreted into the cell culture
      media and purified by anti-soluble porcine TNF-RI antibody and protein G affinity
      chromatography, respectively. The yield of protein using this method was
      approximately 1.5mg rspTNF-RI and 4mg rspTNF-RI-IgG/L of cell culture medium. In
      in vitro assays, rspTNF-RI-IgG was approximately 10-fold (0.97 vs. 10.00pmol/ml)
      more effective than rspTNF-RI at completely inhibiting the cytotoxic activity of
      500U of recombinant porcine TNF-alpha on 3 x 10(4) WEHI 164 murine fibrosarcoma,
      clone 13, cells. Compared to previously described methods, this method yields
      significantly more biologically active rspTNF-RI.

PMID- 12007892
TI  - Abstracts of the Workshop: Non Invasive Investigation of Muscle Function.
      Marseille, France, October 4-6, 2001.

PMID- 12007894
TI  - Androgen insufficiency in women. Proceedings of the Princeton Conference.
      Princeton, New Jersey. July 29, 2001.

PMID- 12007895
TI  - Androgen production in women.
AB  - OBJECTIVE: To describe the sources, production rates, circulating concentrations,
      and regulatory mechanisms of the major androgen precursors and androgens in
      women. DESIGN: Review of the major published literature. RESULT(S):
      Quantitatively, women secrete greater amounts of androgen than of estrogen. The
      major circulating steroids generally classified as androgens include
      dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA),
      androstenedione (A), testosterone (T), and dihydrotestosterone in descending
      order of serum concentration, though only the latter two bind the androgen
      receptor. The other three steroids are better considered as pro-androgens.
      Dehydroepiandrosterone is primarily an adrenal product, regulated by
      adrenocorticotropic hormone (ACTH) and acting as a precursor for the peripheral
      synthesis of more potent androgens. Dehydroepiandrosterone is produced by both
      the ovary and adrenal, as well as being derived from circulating DHEAS.
      Androstenedione and testosterone are products of the ovary and the adrenal.
      Testosterone circulates both in its free form, and bound to protein including
      albumin and sex steroid hormone-binding globulin (SHBG), the levels of which are
      an important determinant of free testosterone concentration. CONCLUSION(S): The
      postmenopausal ovary is an androgen-secreting organ and the levels of
      testosterone are not directly influenced by the menopausal transition or the
      occurrence of menopause. Dihydrotestosterone (DHT) is primarily a peripheral
      product of testosterone metabolism. Severe androgen deficiency occurs in
      hypopituitarism, but other causes may lead to androgen deficiency, including
      Addison's disease, corticosteroid therapy, chronic illness, estrogen replacement
      (leads to elevated SHBG and, therefore, low free testosterone), premenopausal
      ovarian failure, or oophorectomy.

PMID- 12007896
TI  - Aromatization of androgens in women: current concepts and findings.
AB  - OBJECTIVE: To review the role of circulating C(19) steroids as precursors of
      estrogens in postmenopausal women. DESIGN: Review of current published
      literature. RESULT(S): In postmenopausal women as in men, estradiol no longer
      functions as a circulating hormone, because it ceases to be formed by the ovaries
      at the time of menopause. Estradiol continues to be formed in a number of
      extragonadal sites, however, including breast, bone, vascular smooth muscle, and
      various sites in the brain. At these sites of formation, local estradiol levels
      can be quite high, but the production rate is insufficient to affect the body in
      a global fashion; thus, estrogen action at these extragonadal sites of synthesis
      is primarily at a local level and serves a paracrine or even intracrine role.
      Because of this, in postmenopausal women as in men, circulating estrogen levels
      do not drive growth and development of target tissues. Instead, they reflect the
      metabolism of estradiol at these extragonadal sites. Estrogen that is not
      metabolized at these sites reenters the circulation, and, consequently,
      circulating levels of estradiol reflect its synthesis and action in extragonadal
      sites. Thus, they are reactive instead of proactive. An important difference
      between estrogen production at these extragonadal sites and estrogen that is
      synthesized in the ovary is that the former is absolutely dependent on a supply
      of circulating C(19) androgenic substrate. CONCLUSION(S): Circulating levels of
      testosterone begin to decline in the mid-reproductive years, and the levels of
      adrenal androgenic steroids, namely adrostenedione and DHEA, decrease throughout
      postmenopausal life. Therefore, the circulating levels of these adrogenic
      steroids may serve an important role in the maintenance of local estrogen
      synthesis, for example, in the bone and brain where estrogen has a profound
      influence on the maintenance of mineralization on the one hand, and possible
      cognitive function on the other.

PMID- 12007897
TI  - Role of androgens in female genital sexual arousal: receptor expression,
      structure, and function.
AB  - OBJECTIVE: In women, androgens modulate the physiological function of many
      reproductive and sexual organs, including the ovaries, uterus, vagina, oviducts,
      clitoris, and mammary gland. In this article, we review the mechanisms of
      androgen action and discuss new data on the effects of androgens in vaginal and
      clitoral tissues. MAIN OUTCOME MEASURE(S): In this study, we characterized the
      androgen receptor expression in rabbit vaginal tissues from control and
      ovariectomized animals treated with or without androgen replacement therapy. We
      investigated the effects of androgen deprivation and replacement on the
      expression and activity of nitric oxide synthase and arginase and on vaginal
      smooth muscle contractility. RESULT(S): Androgens enhanced nitric oxide synthase
      activity and down-regulated arginase activity in proximal vagina. Estrogens down
      regulated nitric oxide synthase activity and increased arginase activity in
      distal vagina. Androgens facilitated vaginal smooth muscle relaxation to electric
      field stimulation and vasoactive intestinal polypeptide, whereas estrogens
      attenuated vaginal tissue relaxation to electric field stimulation and to
      vasoactive intestinal polypeptide. CONCLUSION(S): These observations suggest that
      androgens may play an important role in modulating the physiology of vaginal
      tissue and contribute to female genital sexual arousal.

PMID- 12007898
TI  - Dehydroepiandrosterone: a springboard hormone for female sexuality.
AB  - OBJECTIVE: To determine the role of adrenal androgenic hormone precursors in
      female sexual function. DESIGN: A review of current literature on sexual function
      and the androgen precursor hormone dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEAS). RESULT(S): The C(19) steroid DHEA is both
      an ovarian and adrenal androgen precursor hormone, whereas DHEAS is only
      synthesized in the adrenal cortex. Dehydroepiandrosterone sulfate secretion
      begins at age 10, peaks at age 20, and then wanes. Low DHEAS levels occur in men
      and women with adrenal insufficiency and in the elderly. Dehydroepiandrosterone,
      50 mg/d, increases DHEAS levels. In women but not men, the increased DHEAS levels
      facilitate additional production of downstream androgens, testosterone,
      dihydrotestosterone, androstenedione, and androstenediol glucuronide. With the
      improved female androgenic profile women with adrenal insufficiency have
      increased sexual thoughts and fantasies as well as an enhancement in mood and
      well-being. In the elderly >age 65 - DHEAS levels increase in both men and women
      with DHEA 50 mg/d but only in women were the higher DHEAS levels accompanied by a
      surge in testosterone levels and in women >age 70 increased libido and enhanced
      sexual satisfaction as well as a 26% diminution in bone resorption, and a 10%
      decrease in skin pigmentation. CONCLUSION(S): The female adrenal androgen
      deficiency syndrome, characterized low serum DHEAS levels may be corrected by
      DHEA supplements that increase levels of DHEAS and downstream androgens of
      importance to female sexuality.

PMID- 12007899
TI  - Androgens and mammary growth and neoplasia.
AB  - OBJECTIVE: Evaluation of current clinical, experimental, genetic, and
      epidemiological data pertaining to the role of androgens in mammary growth and
      neoplasia. DESIGN: Literature review. SETTING: National Institutes of Health.
      SUBJECT(S): Recent, basic, clinical, and epidemiological studies.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Effects of androgens on mammary
      epithelial proliferation and/or breast cancer incidence. RESULT(S): Experimental
      data derived from rodents and cell lines provide conflicting results that appear
      be strain- and cell line-dependent. Epidemiologic studies have significant
      methodological limitations and provide inconclusive results. The study of
      molecular defects involving androgenic pathways in breast cancer is in its
      infancy. Clinical and nonhuman primate studies, however, suggest that androgens
      inhibit mammary epithelial proliferation and breast growth and that conventional
      estrogen treatment suppresses endogenous androgens. CONCLUSION(S): Abundant
      clinical evidence suggests that androgens normally inhibit mammary epithelial
      proliferation and breast growth. Suppression of androgens by conventional
      estrogen treatment may thus enhance estrogenic breast stimulation and possibly
      breast cancer risk. Clinical trials to evaluate the impact of combined estrogen
      and androgen hormone replacement regimens on mammary gland homeostasis are needed
      to address this issue.

PMID- 12007900
TI  - Androgen effects on bone and muscle.
AB  - Bone health and strength are dependent on the coupling of cone resorption and
      bone formation. This process is governed by the interaction of osteoclasts and
      osteoblasts plus the modulating influence of the bone mechanicosensory cells-the
      osteocytes. Both sex steroids-estrogen (E) and testosterone (T)- have receptors
      on all bone cells, with androgen dominance on osteoblasts and osteocytes.
      Specific receptors for the weaker androgens, such as DHEA have also been
      identified. The activity of the sex steroids, influenced by various enzymes found
      in bone, is reflective of the hormone ligand before its binding to the bone
      cells. As a result, T acts both directly and via its aromatization to estradiol.
      The activity of the androgens also varies with the bone surface; periosteal
      cells, for example, do not have 5alpha-reductase activity, indicating that T is
      the active metabolite at this clinically important site. Androgens influence bone
      cell function via local and systemic growth factors and cytokines. By enhancing
      osteoblast differentiation, androgens regulate bone matrix production,
      organization, and mineralization. Androgens also regulate osteoclast recruitment
      and activity. Endogenous androgens increase bone mineral density (BMD) in both
      adolescent and adult premenopausal women. Women with excess endogenous androgen
      for example, those with hirsutism and polycystic ovary syndrome (PCOS)-have
      increased BMD compared with normal young women. E and androgen therapy increases
      BMD to a greater degree than does E therapy alone. This is true for both oral
      combinations of esterified E and methyltestosterone and for subcutaneous T
      implants. Androgenic progestins have an additive effect on BMD when combined with
      E therapy and have the further advantage of being protective to the endometrium
      in E-treated women. Androgens increase muscle mass and strength. The resulting
      improvement in physical activity leads to the activation of bone-forming sites
      and the stimulation of the bone formation-modulating cells, the osteocytes.
      Mechanical loading, when combined with hormone therapy, results in greater
      osteogenic response than does either alone.

PMID- 12007901
TI  - Hormones, mood, sexuality, and the menopausal transition.
AB  - OBJECTIVE: To determine the extent of changes in women's sexual functioning and
      well-being during the menopausal transition and the relationship to hormonal
      changes. DESIGN: Prospective observational study. SETTING: Population-based
      sample assessed at home. PATIENT(S): 438 Australian-born women 45-55 of years who
      were still menstruating at baseline. Of these, 226 were studied for effects of
      hormones on sexual functioning. MAIN OUTCOME MEASURE(S): Short Personal
      Experiences Questionnaire (SPEQ) and Affectometer 2 scores and annual blood
      sampling. RESULT(S): From the early to late menopausal transition, the percentage
      of women with SPEQ scores indicating sexual dysfunction increased from 42% to
      88%. Mood scores did not change significantly. In the early menopausal
      transition, women with low total SPEQ scores had lower estradiol level but
      similar androgen levels to those with higher scores. Decreasing SPEQ scores
      correlated with decreasing estradiol level but not with androgen levels. Hormone
      levels were not related to mood scores. CONCLUSION(S): Female sexual functioning
      declines with the natural menopausal transition. This decline relates more to
      decreasing estradiol levels than to androgen levels.

PMID- 12007902
TI  - Randomized clinical trials of combined estrogen-androgen preparations: effects on
      sexual functioning.
AB  - OBJECTIVE: To review the randomized controlled trials of the efficacy of combined
      estrogen-androgen (E-A) preparations on sexual functioning in postmenopausal
      women. PATIENT(S): Naturally and surgically menopausal women. MAIN OUTCOME
      MEASURE(S): Changes in aspects of sexual functioning. RESULT(S): In general, a
      high degree of agreement exists among the findings of these well-controlled
      trials that combined E-A preparations enhance psychological well-being as well as
      sexual desire and interest and, sometimes, increases the frequency of sexual
      intercourse and orgasm compared with estrogen-alone treatment in both naturally
      and surgically postmenopausal women. CONCLUSION(S): In selected cases, combined E
      A therapy can enhance the quality of life for both naturally and surgically
      postmenopausal women.

PMID- 12007903
TI  - Sexual effects of androgens in women: some theoretical considerations.
AB  - OBJECTIVE: To consider explanations for the inconsistent evidence concerning
      behavioral effects of androgens in women. The following possible explanatory
      mechanisms are explored: [1] Women vary in their behavioral responsiveness to T.
      [2] Some reported effects of exogenous T may be induced by increasing
      bioavailable estrogen. [3] Sexual effects of T may be secondary to direct effects
      on mood. [4] The relationship between T and sexuality is readily obscured by
      psychological mechanisms. [5] Stress-induced increases in adrenal androgens may
      further confuse the picture. [6] Women who respond to T respond to levels that
      are ineffective in men. There is no evidence of a threshold in women above which
      further increases in T have no additional effect. CONCLUSION(S): A theoretical
      model, involving desensitization of the central nervous system to T during early
      development in the male, is presented as a possible explanation for some of these
      relevant differences between men and women and for much of the conflicting
      evidence in the literature on women.

PMID- 12007904
TI  - Androgen deficiency in the oophorectomized woman.
AB  - Women experience a significant decline in circulating androgen concentrations
      after bilateral oophorectomy. Despite several limitations, studying women after
      oophorectomy remains a good model for investigating the effects of both androgen
      deficiency and androgen replacement. Current data show that most women experience
      satisfying sexual lives after hysterectomy and bilateral oophorectomy. This is
      reassuring since elective oophorectomy at the time of hysterectomy is an
      appropriate option for many women. Oophorectomized women, however, are more
      likely to report a worsening of sexual function after hysterectomy compared with
      women who retain their ovaries. Specifically, adverse changes in libido and
      orgasmic response are more likely in oophorectomized women. After bilateral
      oophorectomy, women also appear more likely to experience decreased positive
      psychological well-being. Studies of both the consequences of oophorectomy and
      the effects of testosterone replacement are consistent with an important role for
      androgens in female sexual function and psychological well-being.

PMID- 12007905
TI  - Androgen deficiency: menopause and estrogen-related factors.
AB  - OBJECTIVE: To describe the changes in ovarian hormones caused by natural
      menopause and hormone replacement therapy that have effects on androgen
      bioavailability and to describe indications for androgen replacement in
      postmenopausal women. DESIGN: Review of English language-published research over
      the last 35 years from January 1, 1966 to June 30, 2001 using MEDLINE. SETTING:
      Academic medical center. INTERVENTION(S): None. RESULT(S): In menopausal women,
      the effects of estradiol depletion and replacement on sex hormone-binding
      globulin appear to have clinically significant effects on bioavailable endogenous
      androgens. Many women whose menopause-related symptoms and bone loss responded
      inadequately to estrogen replacement were found to benefit from the addition of
      androgens. Most studies have focused on the sexual benefits of prescribing
      androgens to postmenopausal women. New studies have begun exploring the effects
      of androgens in other body systems, including the brain and the cardiovascular
      system. CONCLUSION(S): Estrogen depletion and replacement therapy at menopause
      can have clinically significant effects on bioavailability of endogenous
      androgens. Androgens complement the actions of estrogens in symptom control and
      disease prevention in postmenopausal women. Although androgen effects on sexual
      function are important, effects of androgens in many body systems should be
      considered in future research to determine optimal postmenopausal hormone
      replacement therapy.

PMID- 12007906
TI  - When to suspect androgen deficiency other than at menopause.
AB  - OBJECTIVE: To review causes of female androgen insufficiency (FAI) other than
      menopause. DESIGN: A review of the available literature in this field. RESULT(S):
      Androgen levels decline with increasing age during the reproductive years in
      healthy women and vary little or not at all across menopause, with controversy as
      to whether levels change in the postmenopausal years. Thus the premenopausal
      decline in androgens potentially is the most common cause of female androgen
      insufficiency (FAI), whereas natural menopause in itself is not a cause of
      androgen deficiency. Pathophysiological causes of FAI can be divided into those
      that affect ovarian androgen production, those that affect adrenal androgen
      production, and combined deficiency states. Surgical menopause is characterized
      by an abrupt onset of symptoms, in contrast to a more insidious onset of
      relatively nonspecific symptoms in women who have FAI due to aging.
      CONCLUSION(S): The decline in testosterone with normal aging before menopause may
      well be the most common cause of FAI, although many women do not present with
      symptoms and most are not diagnosed until they have reached menopause.

PMID- 12007907
TI  - The hypoandrogenic woman: pathophysiologic overview.
AB  - OBJECTIVE: To review the pathophysiologic changes associated with androgen
      insufficiency in the female. DESIGN: A review of the English-language literature
      from 1940 to 2001. CONCLUSION(S): Data suggest that diminished androgen levels,
      most frequently noted in the surgically menopausal patient, may be associated
      with a number of symptoms including reduced sexual libido and desire, loss of
      motivation, flat affect, and reduced energy. Lack of consensus in defining
      abnormally low values for free and total serum androgen levels have made the
      definition of hypoandrogenic states difficult.

PMID- 12007908
TI  - Estrogen replacement therapy: effects on the endogenous androgen milieu.
AB  - OBJECTIVE: To review the impact of exogenous estrogen replacement therapy (ERT)
      on the production, binding, and metabolism of ovarian and adrenal androgens.
      DESIGN: Review of the scientific literature from January 1966 through June 2001
      using MEDLINE. CONCLUSION(S): Although no precipitous drop in androgen production
      is apparent at the time of the menopause, androgens decrease slowly and
      progressively from early adulthood until old age. The impact of aging and of
      estrogen replacement therapy, particularly oral ERT, significantly reduces
      androgen bioavailability after menopause. The combined effects of reduced
      production with aging and the pharmacologic effects of oral ERT dramatically
      reduce the endogenous bioavailable androgen milieu. These changes may have
      adverse clinical implications for susceptible individuals.

PMID- 12007909
TI  - Screening for androgen deficiency in women: methodological and interpretive
      issues.
AB  - OBJECTIVE: To appreciate the problems in obtaining and interpreting androgen
      levels in women. DESIGN: Review of the literature to compare various laboratories
      and methods of analysis of serum androgens. PATIENT(S): Normal control
      populations culled from the literature to compare with patients previously
      reported on by us; data from our laboratory quality control compared with data
      from the literature. RESULT(S): Investigators and laboratories disagree as to the
      best methods of measuring testosterone (T) levels in women. Measuring DHEAS
      levels is much less controversial. CONCLUSION(S): Serum T levels should be
      measured in the morning hours and during the middle third of the menstrual cycle
      in premenopausal women. DHEAS levels may be measured at any time. Androgens
      decrease with age, but age-related levels are not accurate because current
      control populations have never been screened for sexual dysfunction. Such control
      populations need to be obtained.

PMID- 12007910
TI  - Assessment of female sexual dysfunction: review of validated methods.
AB  - OBJECTIVE: To review validated methods for the assessment of female sexual
      function in clinical trials. DESIGN: Evaluation of recent peer-review literature
      on sexual function assessment in women. SETTING: International conference on
      androgen insufficiency in women. PATIENT(S): Women with sexual dysfunction due to
      androgen insufficiency or other causes. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Measures of sexual function in women. RESULT(S): Design and
      measurement problems in the assessment of sexual functioning in women have
      limited clinical trials in female sexual dysfunction. Objective measures, such as
      vaginal photoplethysmography or Duplex ultrasound, have been used in some studies
      but lack standardization and are unsuitable for use in large-scale clinical
      trials. A variety of interview methods, validated questionnaires, and event log
      measures have been used for assessing sexual function in recent trials of
      androgen replacement therapy. Each of these methods has distinct advantages and
      disadvantages, although validated questionnaires have provided the most reliable
      findings to date. Recent Food and Drug Administration guidelines on assessment of
      female sexual function in clinical trials are critically reviewed. CONCLUSION(S):
      Despite their prevalence and clinical significance, sexual problems in women have
      often been neglected in clinical trials. A major obstacle in the design of
      clinical trials in this area has been the need for sensitive and reliable
      measures of outcome. Of the currently available measures, self-reported event
      logs or questionnaires are best suited for research or clinical assessment of
      female sexual function.

PMID- 12007911
TI  - Androgen insufficiency in women: summary of critical issues.
AB  - Critical issues concerning the role of androgens in the physical, sexual, and
      emotional health of women include the following:1. Which androgens best reflect
      the androgen status of women? 2. What form of T should be measured and how? 3. Do
      T levels fall after menopause? 4. What effect does oophorectomy have on T levels?
      5. What is the relationship between T and sexual dysfunction? 6. What constitutes
      androgen insufficiency syndrome? 7. What conditions are associated with androgen
      insufficiency? 8. How should a patient with suspected androgen insufficiency be
      evaluated? 9. Does androgen replacement therapy improve sexual dysfunction? 10.
      Do androgens enhance the quality of life? 11. Is estrogen and androgen therapy
      superior to estrogen therapy alone for low bone mineral density? 12. What are the
      indications for androgen replacement therapy? 13. What is the best means for
      delivery of androgen therapy? 14. How should androgen replacement therapy be
      monitored? Based on our current knowledge, it is clear that some women develop
      symptomatic androgen insufficiency and that androgen replacement therapy has a
      beneficial effect on libido, sexual satisfaction, quality of life, and bone
      mineralization. Androgen replacement therapy should be given the same
      consideration that we give estrogen replacement therapy.

PMID- 12007915
TI  - Ageing and diabetes: implications for brain function.
AB  - Diabetes mellitus is associated with moderate cognitive deficits and
      neurophysiological and structural changes in the brain, a condition that may be
      referred to as diabetic encephalopathy. Diabetes increases the risk of dementia,
      particularly in the elderly. The emerging view is that the diabetic brain
      features many symptoms that are best described as "accelerated brain ageing." The
      clinical characteristics of diabetic encephalopathy are discussed, as well as
      behavioural (e.g. spatial learning) and neurophysiological (e.g. hippocampal
      synaptic plasticity) findings in animal models. Animal models can make a
      substantial contribution to our understanding of the pathogenesis, which shares
      many features with the mechanisms underlying brain ageing. By unravelling the
      pathogenesis, targets for pharmacotherapy can be identified. This may allow
      treatment or prevention of this diabetic complication in the future. We discuss
      changes in glutamate receptor subtypes, in second-messenger systems and in
      protein kinases that may account for the alterations in synaptic plasticity. In
      addition, the possible role of cerebrovascular changes, oxidative stress,
      nonenzymatic protein glycation, insulin and alterations in neuronal calcium
      homeostasis are addressed.

PMID- 12007916
TI  - Inhibition of neuronal nicotinic acetylcholine receptors by La(3+).
AB  - A study was made of the effects of La(3+) on neuronal alpha 2 beta 4 nicotinic
      acetylcholine receptors expressed in Xenopus oocytes. La(3+) by itself (up to 10
      microM) did not elicit significant membrane currents. However, La(3+) reversibly
      inhibited the ionic currents induced by acetylcholine (IC(50)=13.5+/-4.3 microM).
      When La(3+) and acetylcholine were simultaneously applied onto an oocyte, the
      level of inhibition of the acetylcholine response was the same as when the oocyte
      was first preincubated with La(3+) and then exposed to acetylcholine plus La(3+).
      In the presence of La(3+), the EC(50) decreased from 43.8+/-6.4 to 26.5+/-5.1
      microM, suggesting a small increase in the affinity of acetylcholine for the
      receptors through a noncompetitive mechanism. The inhibition of acetylcholine
      response was independent of the membrane potential. From these results we
      conclude that La(3+) regulates nicotinic receptors, reversibly and
      noncompetitively, presumably by inhibiting allosterically the receptor through
      interactions at an external domain of the receptor complex.

PMID- 12007917
TI  - Neuropeptide Y Y(1) receptor regulates protein turnover and constitutive gene
      expression in hypertrophying cardiomyocytes.
AB  - Increased levels of neuropeptide Y correlate with severity of left ventricular
      hypertrophy in vivo. At cardiomyocyte level, hypertrophy is characterised by
      increased mass and altered phenotype. The aims were to determine the
      contributions of increased synthesis and reduced degradation of protein to
      neuropeptide Y-mediated increase in mass, assess effects on gene expression, and
      characterise neuropeptide Y Y receptor subtype involvement. Neuropeptide Y (10
      nM) increased protein mass of adult rat ventricular cardiomyocytes maintained in
      culture (24 h) (16%>basal) and de novo protein synthesis (incorporation of
      [(14)C]phenylalanine) (18%>basal). Neuropeptide Y (100 nM) prevented degradation
      of existing protein at 8 h. Actinomycin D (5 microM) attenuated increases in
      protein mass to neuropeptide Y (< or = 1 nM) but not to neuropeptide Y (10 nM).
      [Leu(31), Pro(34)]neuropeptide Y (10 nM), an agonist at neuropeptide Y Y(1)
      receptors, increased protein mass (25%>basal) but did not stimulate protein
      synthesis. Neuropeptide Y-(3-36) (10 nM), an agonist at neuropeptide Y Y(2)
      receptors, increased protein mass (29%>basal) and increased protein synthesis
      (13%>basal), respectively. Actinomycin D (5 microM) abolished the increase in
      protein mass elicited by neuropeptide Y-(3-36) but not that by [Leu(31),
      Pro(34)]neuropeptide Y. BIBP3226 [(R)-N2-(diphenylacetyl)-N-(4
      hydroxyphenylmethyl)-D-arginine amide] (1 microM), a neuropeptide Y Y(1) receptor
      subtype-selective antagonist, and T(4) [neuropeptide Y-(33-36)](4), a
      neuropeptide Y Y(2) receptor subtype-selective antagonist, attenuated the
      increase in protein mass to 100 nM neuropeptide Y by 68% and 59%, respectively.
      Neuropeptide Y increased expression of the constitutive gene, myosin light chain
      2 (MLC-2), maximally at 12 h (4.7-fold>basal) but did not induce (t< or = 36 h)
      expression of foetal genes (atrial natriuretic peptide (ANP), skeletal-alpha
      actin and myosin heavy chain-beta). This increase was attenuated by 86% and 51%,
      respectively, by BIBP3226 (1 microM) and T(4) [neuropeptide Y-(33-36)](4) (100
      nM). [Leu(31), Pro(34)]neuropeptide Y (100 nM) (2.4-fold>basal) and peptide YY-(3
      36) (100 nM) (2.3 fold>basal) increased expression of MLC-2 mRNA at 12 h. In
      conclusion, initiation of cardiomyocyte hypertrophy by neuropeptide Y requires
      activation of both neuropeptide Y Y(1) and neuropeptide Y Y(2) receptors and is
      associated with enhanced synthesis and attenuated degradation of protein together
      with increased expression of constitutive genes but not reinduction of foetal
      genes.

PMID- 12007918
TI  - Mitochondrial respiratory chain as a new target for anti-ischemic molecules.
AB  - Vascular diseases like thrombosis, myocardial infarction, cerebral ischemia or
      chronic venous insufficiency affect a high proportion of the population. They are
      all associated with more or less pronounced ischemic conditions. We have
      previously shown that some venotropic drugs display an anti-ischemic activity,
      i.e. they prevent the hypoxia-induced decrease in ATP content in cultured cells.
      The effect is due to the fact that these molecules maintain mitochondrial
      respiratory activity during hypoxia. Among them is bilobalide. Starting from the
      3D structure of bilobalide, we designed new molecules presenting the same
      chemical features. They were synthesized and tested for their biological
      activity. As the parent compound, two of them, malonic acid dicyclopent-2-enyl
      ester (MRC2P119) and 2-oxo-3-oxa-bicyclo[3.1.0]hexane-1-carboxylic acid allyl
      ester (MRC2P57), were able to markedly increase the respiratory control ratio of
      isolated mitochondria. They are able to prevent the inhibition of complex I by
      amytal and of complex III by myxothiazol, but not the uncoupling of the
      respiration by carbonylcyanide m-chlorophenyl hydrazone (m-CCP). Moreover,
      MRC2P119 and MRCP2P57 inhibit, in a dose-dependent way, the hypoxia-induced
      decrease in ATP content in endothelial cells as well as the subsequent activation
      of these cells as evidenced by an inhibition of the increase in neutrophil
      adherence to the endothelial cells induced by hypoxia. Finally, MRC2P119 prevent
      the hypoxia- and the hypoxia-reoxygenation-induced decrease in viability of SH
      SY5Y neuroblastoma cells. In conclusion, we identified two new molecules, which
      display anti-ischemic properties when tested in vitro on endothelial and neuronal
      cell types. This anti-ischemic activity is probably due to a protection of
      complexes I and III of the mitochondrial respiratory chain.

PMID- 12007919
TI  - Adenosine receptor-mediated control of in vitro release of pain-related
      neuropeptides from the rat spinal cord.
AB  - Although it is well established that adenosine exerts antinociceptive effects at
      the spinal level in various species including human, the mechanisms responsible
      for such effects are still a matter of debate. We presently investigated whether
      adenosine-induced antinociception might possibly be related to an inhibitory
      influence of this neuromodulator on the spinal release of neuropeptides
      implicated in the transfer and/or control of nociceptive signals. For this
      purpose, the K(+)-evoked overflow of substance P-, calcitonin gene-related
      peptide (CGRP)- and cholecystokinin-like materials was measured from slices of
      the dorsal half of the rat lumbar enlargement superfused with an artificial
      cerebrospinal fluid supplemented with increasing concentrations of various
      adenosine receptor ligands. The data showed that stimulation of adenosine A(1)
      and (possibly) A(3) receptors, but not A(2A) receptors, exerted an inhibitory
      influence on the spinal release of CGRP-like material. In contrast, none of the
      adenosine A(1), A(2A) and A(3) receptor agonists tested within relevant ranges of
      concentrations significantly affected the release of substance P- and
      cholecystokinin-like materials. These results support the idea that adenosine
      induced antinociception at the spinal level might possibly be caused, at least
      partly, by the stimulation of inhibitory adenosine A(1) receptors located
      presynaptically on primary afferent fibres containing CGRP but not substance P.

PMID- 12007920
TI  - Dual effect of local application of nitric oxide donors in a model of incision
      pain in rats.
AB  - The effects of local application of a cream containing nitric oxide (NO) donors,
      S-nitroso-N-acetylpenicillamine (SNAP) or isosorbide dinitrate were studied in a
      rat model of incision pain. An incision was made in the plantar aspect of a hind
      paw and the cream was applied inside the surgical wound. SNAP (1-10%) or
      isosorbide (2.5-5%) reduced the incision allodynia as measured with von Frey
      filaments. Higher concentrations produced a smaller or no effect, but SNAP (30%)
      intensified the allodynia. Allodynia was also intensified by SNAP (5% or 30%) in
      rats pretreated with intraplantar 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one
      (ODQ, 4 microg), a guanylate cyclase inhibitor. The effect of isosorbide (5%) was
      prevented by ODQ. The cream containing SNAP released 10- to 20-fold more nitrite
      than did isosorbide from a macrophage culture. We conclude that local application
      of drugs generating a low NO concentration reduces incision pain through
      activation of guanylate cyclase. Drugs generating high NO concentrations,
      however, intensify pain via a guanylate cyclase-independent mechanism.

PMID- 12007921
TI  - Effects of nefopam on the spinal nociceptive processes: a c-Fos protein study in
      the rat.
AB  - We have evaluated the effects of nefopam on the spinal c-Fos protein expression
      in the model of acute (noxious heat) and persistent (intraplantar injection of
      formalin) nociception in the rat. One and two hours after i.pl. formalin
      injection, c-Fos immunoreactive (c-Fos-IR) nuclei were preferentially located in
      the superficial (I-II) and deep (V-VI) laminae of the spinal dorsal horn of
      segments L4-L5, i.e. spinal areas containing numerous neurons responding
      exclusively, or not, to peripheral nociceptive stimuli. The doses of 15 and 30
      mg/kg (s.c.) of nefopam had significant reducing effects on the formalin-evoked
      spinal c-Fos protein expression (36+/-14% and 47+/-9% reduction of the total
      number of c-Fos-IR nuclei per section, respectively, P<0.05 for both). These
      reducing effects of nefopam were not detectable 2 h after formalin. These results
      provide evidence that the significant effects of nefopam are time-limited in the
      formalin model of persistent nociception. One hour after noxious heat stimulation
      (52 degrees C for 15 s), c-Fos-IR nuclei were principally located in the
      superficial laminae I-II of the spinal dorsal horn (about 90% of the total number
      of c-Fos-IR nuclei per section). Nefopam (15 mg/kg s.c.) significantly reduced
      the noxious heat-evoked spinal c-Fos protein expression (33+/-3% reduction of the
      total number of c-Fos-IR nuclei, P<0.0001). The present results provide first
      evidence for the reducing effects of nefopam on the noxiously evoked spinal c-Fos
      protein expression, principally in acute nociceptive processes. These results
      suggest that nefopam may produce antinociceptive effects mainly in acute pain
      states.

PMID- 12007922
TI  - Behavioral sensitization is greater after repeated versus single chronic cocaine
      dosing regimens.
AB  - Cocaine dosing regimens in animals are used to model behavioral and neurochemical
      changes in human cocaine abusers. Typically, rats are dosed for 5-14 days and
      assessed at some point during withdrawal. However, human cocaine bingers undergo
      multiple periods of several days of abuse. Here, we model the human binge pattern
      by giving rats two separate cocaine dosing regimens which results in greater
      behavioral sensitization than a single cocaine dosing regimen. This model also
      allows for the testing of drugs in reversal of a previously established
      sensitization. Multiple cocaine regimens may thus provide a better model for the
      human condition.

PMID- 12007923
TI  - Effects of intracerebroventricular administration of the CCK(1) receptor
      antagonist devazepide on food intake in rats.
AB  - The effects of intracerebroventricular administration of devazepide, a CCK(1)
      receptor antagonist, was investigated on food intake in rats. In the first
      experiment, rats (n=5) were deprived of food for 17 h and injected
      intracerebroventricularly with either vehicle or devazepide (1, 10, 25 or 100
      ng). Five minutes after vehicle or drug administration, the animals were
      presented with food and intake measured for 60 min. Devazepide produced a dose
      related increase in food intake. Doses of 1, 10 and 25 ng significantly increased
      consumption (at least P<0.01 in each case). A second experiment was subsequently
      undertaken to investigate whether systemic administration of the
      intracerebroventricular doses used in the first experiment would affect food
      intake. Rats (n=8) that have been deprived of food for 17 h were injected
      intraperitoneally with either vehicle or devazepide (3, 30, 75 or 300 ng/kg).
      Five minutes after vehicle or drug administration, the animals were presented
      with food and intake was measured for 60 min. Devazepide (3-300 ng/kg, i.p.) had
      no significant effects on food consumption. The results show that central
      administration of low doses of devazepide increase food intake in rats, while
      similar doses, given systemically, do not affect consumption. These findings
      suggest the possibility that endogenous cholecystokinin (CCK), acting at central
      CCK(1) receptors, may play a physiological role in the control of feeding
      behaviour in the rat.

PMID- 12007924
TI  - Modulation by hydrogen peroxide of noradrenaline-induced contraction in aorta
      from streptozotocin-induced diabetic rat.
AB  - Hydrogen peroxide (H(2)O(2)) is known to modify vascular tone in various
      preparations and its production is elevated in the diabetic aorta. We have
      investigated its possible involvement in regulation of the noradrenaline-induced
      contractile response in aorta from streptozotocin-induced diabetic rats. In
      diabetic but not in control aorta, the noradrenaline-induced contraction was
      significantly enhanced by catalase and significantly inhibited by polyethylene
      glycolated superoxide dismutase. Adding catalase to the superoxide dismutase
      prevented the latter's attenuation of the contraction. In the presence of N(G)
      nitro-L-arginine, the noradrenaline-induced contraction of aorta from diabetic
      rats, but not from controls, was inhibited by catalase treatment. Noradrenaline
      increased the nitrite and nitrate levels in the perfusates from control and
      diabetic aortic strips. In the latter, the noradrenaline-induced nitrite and
      nitrate level was significantly enhanced by incubation with superoxide dismutase
      but not by incubation with catalase plus superoxide dismutase. Thus, endogenously
      produced H(2)O(2) may be an important factor in the regulation of aortic tone in
      diabetic rats. Enhanced production of H(2)O(2) in the aorta from diabetic rats
      may seem contribute to the endothelial generation of nitric oxide and
      vasoconstrictor prostanoids.

PMID- 12007925
TI  - Cannabinoid CB(1) receptor blockade enhances the protective effect of
      melanocortins in hemorrhagic shock in the rat.
AB  - Activation of peripheral cannabinoid CB(1) receptors contributes to hemorrhagic
      hypotension, and endocannabinoids produced by macrophages and platelets may be
      mediators of this effect. A number of studies have provided evidence that
      functional links exist in the mechanisms of action of cannabinoids and opioid
      peptides; and opioids too play an important role in the pathophysiology of
      hemorrhagic hypotension and shock. On the other hand, melanocortin peptides,
      which are the main endogenous functional antagonists of opioid peptides, have an
      antishock effect in animals and humans. Thus, we investigated whether an
      interaction exists between endocannabinoids and the endogenous opioid/antiopioid
      system also in a condition of hemorrhagic shock and, particularly, whether the
      blockade of cannabinoid CB(1) receptors potentiates the antishock effect of
      melanocortins. Urethane-anesthetized rats were stepwise bled until mean arterial
      pressure decreased to, and stabilized at, 21-23 mm Hg. In this model of
      hemorrhagic shock, which caused the death of all control rats within 30 min after
      vehicle (tween 80, 5% in saline) injection, the intravenous (i.v.) bolus
      injection of the cannabinoid CB(1) receptor antagonist N-piperidino-5-[4
      chlorophenyl]-1-[2,4 dichlorophenyl]-4-methyl-3-pyrazolecarboxamide (SR141716A)
      increased mean arterial pressure, pulse pressure, respiratory rate and survival
      rate in a dose-related manner (0.1-3 mg/kg), an almost complete recovery of mean
      arterial pressure, pulse pressure and respiratory rate, and 100% survival at the
      end of the observation period (2 h), occurring with the dose of 3 mg/kg. The
      melanocortin ACTH-(1-24) (adrenocorticotropin) also produced in a dose-related
      manner (0.02-0.16 mg/kg i.v.) a restoration of cardiovascular and respiratory
      functions, and increased survival rate, an almost complete recovery and 100%
      survival at the end of the observation period (2 h) occurring with the dose of
      0.16 mg/kg. When a subactive dose of SR141716A (0.2 mg/kg; 30% survival) was
      associated with a subactive dose of ACTH-(1-24) (0.02 mg/kg; 12% survival), a
      complete reversal of the shock condition was obtained with 100% survival at the
      end of the 2-h observation period. The present results show that the concurrent
      inhibition of both endogenous opioid and cannabinoid systems produces a reversal
      of hemorrhagic shock more effective than that produced by the inhibition of
      either of them. These data suggest that functional interactions between
      endocannabinoids and opioid/antiopioid are at work also in the pathophysiology of
      hemorrhagic shock.

PMID- 12007926
TI  - Angiotensin converting enzyme inhibition prevents trophic and hypertensive
      effects of an antagonist of adenosine receptors.
AB  - The continuous infusion of 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), a non
      selective antagonist of adenosine receptors, causes hypertension and marked
      cardiovascular structural changes in Wistar rats. Adenosine inhibits
      noradrenaline and renin release. We investigated the effects of sympathetic
      denervation, evaluated renin activity and the influence of angiotensin converting
      enzyme inhibition in DPSPX-treated rats. Captopril was given (30 or 100 mg kg(-l)
      day(-l); p.o.) from day -l to day 28. On day 0, constant infusions of DPSPX (90
      microg kg(-l) h(-l); i.p.) or vehicle were started. On day 28, fragments of the
      left ventricle, mesenteric and tail arteries were processed for morphological
      studies. Plasma renin activity was increased in DPSPX-treated animals.
      Sympathetic denervation delayed and partially prevented blood pressure rise.
      Angiotensin converting enzyme inhibition prevented DPSPX-induced hypertension and
      morphological changes. Our results, although pointing to the involvement of the
      sympathetic system, suggest that other mechanisms are involved. We could not
      differentiate between the trophic and anti-hypertensive effects of angiotensin
      converting enzyme inhibition.

PMID- 12007927
TI  - Gastric acid secretion stimulated by centrally injected nociceptin in urethane
      anesthetized rats.
AB  - Nociceptin is a preferred endogenous ligand for the orphan opioid receptor-like 1
      (ORL1) receptor. Central administration of nociceptin showed various
      pharmacological effects on analgesia, cardiovascular and renal responses, food
      intake, and so on. In the present study, we investigated the effect of nociceptin
      injected into the central nervous system (CNS) on gastric acid secretion in the
      perfused stomach of urethane-anesthetized rats. Injection of nociceptin (0.55
      5.52 nmol per rat) into the fourth cerebroventricle stimulated gastric acid
      secretion and the secretion was inhibited in atropine-treated (1 mg/kg, i.v.) and
      vagotomized rats. The secretion induced by nociceptin (1.65 nmol) was not
      inhibited by the central injection of naloxone (275 nmol, a non-selective
      antagonist of opioid receptors). The secretion was significantly inhibited by the
      central injection of [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2)
      ([F/G]nociceptin-(1-13), 0.21 nmol, an antagonist of ORL1 receptor), although
      [F/G]nociceptin-(1-13) alone at higher doses (2.10 and 7.31 nmol) markedly
      stimulated gastric acid secretion. In the 0-40 min period, the secretion induced
      by nociceptin was inhibited at least partially by CompB (68.8 nmol, a nonpeptidic
      antagonist of ORL1 receptor). Injection of nociceptin (5.52 nmol) into the
      lateral cerebroventricle also stimulated the secretion. Injection of nociceptin
      did not modify gastric acid secretion stimulated by 2-deoxy-D-glucose (200 mg/kg,
      i.v.). In conclusion, nociceptin injected into the CNS stimulated gastric acid
      secretion in rats via the ORL1 receptors and through mechanisms involving the
      vagus nerve.

PMID- 12007928
TI  - The levels of norharman are high enough after smoking to affect monoamineoxidase
      B in platelets.
AB  - Epidemiological studies suggest that smoking reduces the risk for Parkinson's
      disease. It has been hypothesized that inhibition of monoamineoxidase contributes
      to this action. The present study examined the contribution of the beta
      carbolines norharman, an inhibitor of monoamineoxidase B, and harman, an
      inhibitor of monoamineoxidase A, which are present in high concentrations in
      tobacco smoke to the protective action. Nineteen active smokers and five
      nonsmokers smoked one and two cigarettes. The levels of norharman and harman
      increased in plasma from smokers and nonsmokers. Ex vivo saturation kinetic
      experiments revealed that the baseline affinity constant of monoamineoxidase in
      platelets from smokers was higher than that of nonsmokers in contrast to the
      maximum turnover rate, which did not differ. Acute smoking affected the
      monoamineoxidase in nonsmokers only. It is discussed that inhibition of both
      isoforms of monoamineoxidase is necessary for the neuroprotection and that both
      norharman and harman play an important role.

PMID- 12007933
TI  - Intensity-modulated radiotherapy of head-and-neck cancer: encouraging early
      results.

PMID- 12007934
TI  - Barriers to winning the battle with head-and-neck cancer.

PMID- 12007935
TI  - New directions in brachytherapy.

PMID- 12007936
TI  - Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an
      update of the UCSF experience.
AB  - PURPOSE: To update our experience with intensity-modulated radiotherapy (IMRT) in
      the treatment of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between
      April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University
      of California-San Francisco (UCSF). There were 20 females and 47 males, with a
      mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12
      (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using
      three different techniques: 1) manually cut partial transmission blocks, 2)
      computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3)
      sequential tomotherapy using a dynamic multivane intensity modulating collimator
      (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum
      and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients
      had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient
      had gamma knife radiosurgery boost after external beam radiotherapy. The
      prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck
      nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically
      negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy
      boost. Acute and late normal tissue effects were graded according to the
      Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The
      local progression-free, local-regional progression-free, distant metastasis-free
      rates, and the overall survival were calculated using the Kaplan-Meier method.
      RESULTS: With a median follow-up of 31 months (range 7 to 72 months), there has
      been one local recurrence at the primary site. One patient failed in the neck.
      Seventeen patients developed distant metastases; 5 of these patients have died.
      The 4-year estimates of local progression-free, local-regional progression-free,
      and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year
      estimate of overall survival was 88%. The worst acute toxicity documented was as
      follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1
      patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15
      patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after
      IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0
      xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41
      evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no
      xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average
      maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to
      the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of
      the GTV and 3% of the CTV received less than 95% of the prescribed dose.
      CONCLUSION: Excellent local-regional control for NPC was achieved with IMRT. IMRT
      provided excellent tumor target coverage and allowed the delivery of a high dose
      to the target with significant sparing of the salivary glands and other nearby
      critical normal tissues.

PMID- 12007937
TI  - Objective assessment of swallowing dysfunction and aspiration after radiation
      concurrent with chemotherapy for head-and-neck cancer.
AB  - PURPOSE: To objectively assess swallowing function after an intensive
      chemoradiation regimen for locally advanced head-and-neck cancer and to assess
      the clinical implications of swallowing dysfunction. PATIENTS AND METHODS: Twenty
      nine patients with nonresectable Stage IV head-and-neck cancer participated in a
      Phase I study of radiation, 70 Gy/7 weeks, concurrent with weekly gemcitabine.
      Because of a high rate of mucosal toxicity, reduced drug doses were delivered to
      subsequent patient groups: 300, 150, 50, and 10 mg/m(2)/week. Twenty-six of these
      patients underwent prospective evaluation of swallowing function with
      videofluoroscopy and esophagogram. Studies were performed pretherapy, early post
      therapy (1-3 months), and late post-therapy (6-12 months). RESULTS: Complete
      tests were performed pretherapy in 22 patients, early post-therapy in 20, and
      late post-therapy in 13. Twenty-five patients had at least one post-therapy
      study. Post-therapy dysfunction was characterized by reduced inversion of the
      epiglottis, delayed swallow initiation and uncoordinated timing of the propulsion
      of the bolus, opening of the cricopharyngeal muscle, and closure of the larynx,
      all of which promoted aspiration during and after the swallow. In addition,
      reduced base-of-tongue retraction with reduced contact to the posterior
      pharyngeal wall and incomplete cricopharyngeal relaxation resulted in pooling in
      the pyriform sinuses and vallecula of residue, which was frequently aspirated
      after the swallow. Post-therapy aspirations were typically "silent," eliciting no
      cough reflex, or the cough was delayed and noneffective in expelling the residue.
      Aspiration was observed in 3 patients (14%) in the pretherapy studies, in 13
      (65%) in the early post-therapy studies, and in 8 (62%) in the late post-therapy
      studies (aspiration rates post-therapy vs. pretherapy: p = 0.0002). Six patients
      had pneumonia requiring hospitalization 1-14 months after therapy (median: 2.5
      months), being the likely cause of death in 2 patients. Five cases of pneumonia
      occurred among 17 patients who had demonstrated aspiration in the post-therapy
      studies, compared with no cases of pneumonia among 8 patients who had not
      demonstrated aspiration (p = 0.1). Of the 4 patients who had not undergone any
      post-therapy study, 1 developed pneumonia. Mucositis scores, prolonged tube
      feeding, presence of tracheostomy tube, and gemcitabine doses were not found to
      be related to aspiration or pneumonia risk. CONCLUSIONS: After intensive
      chemoradiotherapy, significant objective swallowing dysfunction is prevalent. It
      promotes aspiration, which may not elicit a cough reflex and may be associated
      with pneumonia. Aspiration pneumonia may be an underdocumented complication of
      chemoradiotherapy for head-and-neck cancer. Future studies should examine whether
      routine post-therapy videofluoroscopy and training aspirating patients in safe
      swallowing strategies can reduce this risk.

PMID- 12007938
TI  - Role of brachytherapy in treatment of epidermoid carcinomas of the vallecula
      after conservative supraglottic laryngectomy followed by irradiation.
AB  - PURPOSE: To evaluate survival and functional results of the treatment of
      carcinomas of the vallecula using surgery, irradiation, and interstitial
      brachytherapy. METHODS AND MATERIALS: Between 1990 and 1998, 36 patients with
      squamous cell carcinoma of the vallecula were treated with horizontal
      supraglottic functional laryngectomy, external beam radiotherapy (median dose 54
      Gy), and additional interstitial brachytherapy (median dose 16 Gy). Results were
      compared with a previous series of 22 patients treated without brachytherapy.
      RESULTS: The median follow-up was 44 months. The 5-year actuarial overall
      survival rate was 61.3%. The 5-year specific survival rate was 86%, with 2 local
      failures (local control rate 94.4%) and 4 isolated distant metastases. Ten
      patients developed a second primary. The overall survival was 34% for 22 patients
      previously treated without brachytherapy. Severe toxicities occurred in 9
      patients: death (related to larynx edema or inhalation, n = 1), soft tissue
      necrosis (n = 1), aspiration pneumonia (n = 1), mandibular necrosis (n = 2),
      pharyngocutaneous fistula (n = 2), and laryngeal edema (n = 2). All the patients
      fed orally with no definitive gastrostomy or tracheotomy. CONCLUSION: Additional
      brachytherapy for vallecula carcinoma seems to improve locoregional control and
      overall survival dramatically. Functional results were also excellent. To our
      knowledge, this original therapeutic schedule has never been previously
      described.

PMID- 12007939
TI  - Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with
      carbon ions.
AB  - PURPOSE: Compared to photon irradiation, carbon ions provide physical and
      biologic advantages that may be exploited in chordomas and chondrosarcomas.
      METHODS AND MATERIALS: Between August 1998 and December 2000, 37 patients with
      chordomas (n = 24) and chondrosarcomas (n = 13) were treated with carbon ion
      radiotherapy within a Phase I/II trial. Tumor conformal application of carbon ion
      beams was realized by intensity-controlled raster scanning with pulse-to-pulse
      energy variation. Three-dimensional treatment planning included biologic plan
      optimization. The median tumor dose was 60 GyE (GyE = Gy x relative biologic
      effectiveness). RESULTS: The mean follow-up was 13 months. The local control rate
      after 1 and 2 years was 96% and 90%, respectively. We observed 2 recurrences
      outside the gross tumor volume in patients with chordomas. Progression-free
      survival was 100% for chondrosarcomas and 83% for chordomas at 2 years. Partial
      remission after carbon ion radiotherapy was observed in 6 patients. Treatment
      toxicity was mild. CONCLUSION: These are the first data demonstrating the
      clinical feasibility, safety, and effectiveness of scanning beam delivery of ion
      beams in patients with skull base tumors. The preliminary results in patients
      with skull base chordomas and low-grade chondrosarcomas are encouraging, although
      the follow-up was too short to draw definite conclusions concerning outcome. In
      the absence of major toxicity, dose escalation might be considered.

PMID- 12007940
TI  - Stereotactically guided conformal radiotherapy for progressive low-grade gliomas
      of childhood.
AB  - PURPOSE: To describe the rationale, technique, and early results of
      stereotactically guided conformal radiotherapy (SCRT) in the treatment of
      progressive or inoperable low-grade gliomas (LGGs) of childhood. METHODS AND
      MATERIALS: Between September 1994 and May 1999, 14 children (median age 6 years,
      range 5-16) with LGG were treated with SCRT at the Royal Marsden NHS Trust.
      Tumors were located at the optic chiasm (n = 9), third ventricle (n = 2),
      hypothalamus, craniocervical junction, and pineal region (each n = 1). Four
      patients received chemotherapy before SCRT. Immobilization was in a Gill-Thomas
      Cosman frame (n = 12) and subsequently in a specially designed pediatric version
      of the frame (n = 2). Stereotactic coordinates and the tumor were defined by CT
      scanning with a fiducial system and MRI fusion. The median tumor volume was 19.5
      cm(3) (range 7.5-180). The planning target volume was defined as the area of
      enhancing tumor plus a 5-10-mm margin. The treatment technique consisted of 4
      isocentric, noncoplanar, conformal, fixed fields. Treatment was delivered in 30
      33 daily fractions to a total dose of 50-55 Gy. RESULTS: SCRT was well tolerated,
      with transient hair loss the only acute toxicity. The median follow-up was 33
      months (range 2-53). At 6 months after SCRT, 4 of 12 children with neurologic
      deficits improved and 5 remained stable. Twelve children were available for MRI
      evaluation. Two had a complete response, 6 a partial response, and 4 stable
      disease. One child with optic chiasm glioma had local progression at 25 months,
      and 1 developed diffuse leptomeningeal disease without local progression at 27
      months. The 3-year local progression-free survival and overall survival rate
      after SCRT was 87% and 100%, respectively, compared with 89% and 98% for an
      historic control treated with conventional RT. New endocrine deficiencies were
      noted in 2 children after a follow-up of 20 and 23 months. CONCLUSION: SCRT is a
      feasible, high-precision technique of RT for children with LGGs for whom RT is
      considered appropriate. The local control and acute toxicity of SCRT are
      comparable to a historic control of patients with conventionally delivered RT.
      The frequency of delayed hypothalamic-pituitary axis dysfunction reflects tumor
      location adjacent to the hypothalamus and pituitary. Additional follow-up is
      required to demonstrate that SCRT contributes to a reduction in treatment-related
      late toxicity, while maintaining the local control achieved with conventionally
      delivered RT in children with progressive LGGs.

PMID- 12007941
TI  - Influence of tumor grade on time to progression after irradiation for localized
      ependymoma in children.
AB  - PURPOSE: To investigate the influence of histologic grade on progression-free
      survival (PFS) after irradiation (RT) for pediatric patients with localized
      ependymoma. METHODS AND MATERIALS: Fifty patients with localized ependymoma
      (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT
      between December 1982 and June 1999. Anaplastic features were identified in 14 of
      50 patients. The extent of resection was characterized as gross-total in 36
      patients, near-total in 5, and subtotal in 9. The median dose to the primary site
      was 54 Gy. Of the 50 patients, 23 received pre-RT chemotherapy. RESULTS: Thirty
      nine patients were alive at a median follow-up of 46 months (range 21-214) from
      diagnosis. Thirty-four patients remained progression free at a median follow-up
      of 35 months (range 13-183) after the initiation of RT. Progression occurred in
      16 patients (12 local and 4 local and distant), with a median time to failure of
      21.2 months (range 4.6-65.0). The tumor grade significantly influenced the PFS
      after RT (p < 0.0005). The estimated 3-year PFS rate was 28% +/- 14% for patients
      with anaplastic ependymoma compared with 84% +/- 8% for patients with
      differentiated ependymoma. These results remained significant when corrected for
      age at diagnosis (<3 years), pre-RT chemotherapy, and extent of resection.
      Patients who received pre-RT chemotherapy had an inferior 3-year PFS estimate
      after RT (49 +/- 12%) compared with those who did not (84% +/- 10%; p = 0.056).
      Anaplastic ependymoma was found more frequently in the supratentorial brain (p =
      0.002). Six of 12 patients with supratentorial tumor developed recurrence;
      recurrence was restricted to patients with anaplastic ependymoma. CONCLUSION:
      Tumor grade influences outcome for patients with ependymoma independent of other
      factors and should be considered in the design and analysis of prospective trials
      involving pediatric patients treated with RT. Chemotherapy before RT influences
      the PFS and overall survival after RT. The effect is more pronounced when
      progression occurs during chemotherapy.

PMID- 12007942
TI  - Phase II study of accelerated fractionation radiation therapy with carboplatin
      followed by PCV chemotherapy for the treatment of anaplastic gliomas.
AB  - PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy
      and safety of accelerated fractionated radiotherapy combined with i.v.
      carboplatin for patients with previously untreated anaplastic gliomas. METHODS
      AND MATERIALS: Between 1988 and 1992, 90 patients received 1.9-2.0-Gy radiation 3
      times a day with 2-h infusions of 33 g/m(2) carboplatin for two 5-day cycles
      separated by 2 weeks. After radiotherapy, patients received procarbazine,
      lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed.
      RESULTS: Ninety patients were evaluable for analysis. Histologically, 69 had
      anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic
      oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal
      resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal
      resection) was performed in 50 (56%) patients. A multivariate analysis showed
      that a younger age (p = 0.026), Karnofsky performance score (KPS; p = 0.009), and
      brain necrosis (p = 0.0002) were predictive of a better survival. Results from
      analysis of extent of surgery (biopsy, subtotal resection, gross total resection)
      approached significance (p = 0.058). Radiation dose, irradiated tumor volume, and
      techniques used (boost and fields) were not significant variables. The median
      survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic
      astrocytoma patients, MS was 28.7 months and 40.8 months for the combined
      anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival
      occurred in 25% of anaplastic glioma patients who were alive 8.6 years after
      treatment was initiated. Treatment-induced necrosis was documented by surgery or
      autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor;
      and an additional 13 (14%) patients who did not have surgical or autopsy
      demonstration of predominant radiation necrosis had magnetic resonance imaging
      (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration
      and/or dementia requiring full-time caregiver attention were observed in 9 (10%)
      patients. CONCLUSION: When comparable selection criteria are applied, the rate of
      MS in this study is inferior to results attainable with current radiation and
      chemotherapy approaches, although the rates of long-term survival are comparable.
      Theoretically, patients failing therapy and dying earlier than anticipated may be
      because of excessive central nervous system (CNS) toxicity resulting from the
      combination of accelerated fractionated irradiation, intensive carboplatin
      chemotherapy before each radiation fraction, and postirradiation PCV
      chemotherapy. On the other hand, patients with treatment-induced necrosis
      survived significantly longer than patients who did not demonstrate MRI or
      histologic evidence of necrosis (MS, 106 months vs. 18-33 months).

PMID- 12007943
TI  - Brachytherapy of glioblastoma recurring in previously irradiated territory:
      predictive value of tumor volume.
AB  - PURPOSE: To evaluate the impact of tumor volume on survival of patients
      reirradiated with (192)Ir for recurrent glioblastoma. METHODS AND MATERIALS:
      Between 1993 and 1997, 42 patients with recurrent glioblastomas (29 males and 13
      females, age 18-69 years, median age 49) were treated with (192)Ir implantation.
      Previous treatments included surgery, external beam radiotherapy, and
      chemotherapy. Maximum diameter of the recurrent tumor was 1.2-10.1 cm (median:
      5.7 cm) and tumor volume was 1.6-122 cm(3) (median: 23 cm(3)). Karnofsky
      performance status score was 50-100 (median: 80). Brachytherapy dose was 40-60
      Gy. RESULTS: Probability of overall survival was 80% at 6 months, 48% at 1 year,
      and 11% at 2 years. Median survival was 50 weeks. Univariate analysis showed that
      both tumor volume (T < or T > or = 30 cm(3)) and Karnofsky performance status
      score were significant predictors of survival. Multivariate analysis showed that
      smaller tumor volumes were associated with a higher probability of survival (p <
      0.001). CONCLUSION: Tumor volume less than 30 cm(3) was associated with a higher
      probability of, and quality of, survival than larger lesions for patients
      reirradiated by brachytherapy for recurrent glioblastoma.

PMID- 12007944
TI  - Factors affecting risk of symptomatic temporal lobe necrosis: significance of
      fractional dose and treatment time.
AB  - PURPOSE: To study the factors affecting the risk of symptomatic temporal lobe
      necrosis after different fractionation schedules. METHODS AND MATERIALS: One
      thousand thirty-two patients with T1-2 nasopharyngeal carcinoma treated with
      radical radiotherapy in Hong Kong during 1990-1995 were studied. They were
      treated at four different centers with similar techniques but different
      fractionation schedules: 984 patients were given 1 fraction daily throughout
      (q.d.), and 48 patients were irradiated twice daily (b.i.d.) for part of the
      course. The median total dose was 62.5 Gy (range 50.4-71.2), dose per fraction
      was 2.5 Gy (range 1.6-4.2), and overall treatment time (OTT) was 44 days (range
      29-70). In addition, 500 patients received supplementary doses for parapharyngeal
      extension, 113 received booster doses by brachytherapy, and 114 received
      sequential chemotherapy using cisplatin-based regimes. RESULTS: Altogether, 24
      patients developed symptomatic temporal lobe necrosis: 18 from the q.d. group and
      6 from the b.i.d. group. The 5-year actuarial incidence ranged from 0% (after 66
      Gy in 33 fractions within 44 days) to 14% (after 71.2 Gy in 40 fractions within
      35 days). Multivariate analyses showed that the risk was significantly affected
      by the fractional effect of the product of total dose and dose per fraction
      (hazard ratio [HR] = 1.04, 95% confidence interval [CI] 1.02-1.05), OTT (HR 0.88,
      95% CI 0.80-0.97), and b.i.d. scheduling (HR 13, 95% CI 3-54). Repeating the
      analyses for patients treated with the q.d. schedules confirmed the independent
      significance of OTT in addition to the product of total dose and dose per
      fraction. CONCLUSION: The tentative results suggest that in addition to
      fractional dose, the OTT also had significant impact on the risk of temporal lobe
      necrosis, and b.i.d. scheduling increased the hazard further.

PMID- 12007945
TI  - Late radiation effects on hearing, vestibular function, and taste in brain tumor
      patients.
AB  - PURPOSE: To investigate late radiation effects on hearing, vestibular function,
      and taste after conventional radiotherapy in brain tumor patients. METHODS AND
      MATERIALS: Hearing, vestibular function, and taste were assessed in 33 brain
      tumor patients irradiated unilaterally to the tumor-bearing hemisphere and the
      temporal bone. Median observation time after completion of radiotherapy was 13
      years; the fraction dose was 1.8 Gy, and mean radiation dose was 53.1 Gy.
      RESULTS: Deep ulceration in the external ear canal and osteoradionecrosis on the
      irradiated side was seen in three patients. Reduced hearing was found for air and
      bone conduction of the irradiated side compared to the opposite side (0.25-2 kHz:
      6.1 dB, 4 kHz: 10.3 dB, 6 kHz: 15.6 dB, and 8 kHz: 16.5 dB). For bone conduction,
      the corresponding figures were 0.25-2 kHz: 5.5 dB and 4 kHz: 8.2 dB. Three
      patients had a canal paresis of the irradiated side, and three patients had
      affection of the chorda tympani. CONCLUSION: Irradiation of the temporal bone
      with doses usually given in the treatment of patients with brain tumors may cause
      osteoradionecrosis, sensorineural hearing loss, dysfunction of the vestibular
      inner ear, and loss of taste. Head-and-neck examination should be included in the
      follow-up of long-term survivors.

PMID- 12007946
TI  - Predictive factors of urinary retention following prostate brachytherapy.
AB  - PURPOSE: To evaluate the incidence and duration of urinary retention requiring
      catheterization and the factors predictive for these end points. METHODS AND
      MATERIALS: Two hundred eighty-two patients treated with prostate brachytherapy
      alone were evaluated. Clinical and treatment-related factors examined included:
      age, baseline International Prostate Symptom Score (IPSS), presence of
      comorbidity, planning ultrasound target volume (PUTV), postimplant prostate CT
      scan volume, the CT:PUTV ratio, number of seeds inserted, number of needles used,
      use of neoadjuvant hormones, procedural physician, clinical stage, Gleason score,
      and pretreatment PSA. Dosimetric quality indicators were also examined. RESULTS:
      Urinary obstruction after prostate brachytherapy developed in 43 (15%) patients.
      The median duration of catheter insertion was 21 days (mean 49, range 1-365).
      Univariate analysis demonstrated that presence of diabetes, preimplant volume,
      postimplant volume, CT:PUTV ratio, number of needles, and dosimetric parameters
      were predictive for catheterization. However, in multivariate analysis, only the
      baseline IPSS, CT:PUTV ratio, and presence of diabetes were significant
      independent predictive factors for catheterization. CONCLUSION: Baseline IPSS was
      the most important predictive factor for postimplantation catheterization. The
      extent of postimplant edema, as reflected by the CT:PUTV ratio, predicted for
      need and duration of catheterization. The presence of diabetes was predictive for
      catheterization, but may relate to the absence of prophylactic steroids, and
      therefore requires further evaluation.

PMID- 12007947
TI  - Gastrointestinal toxicity of transperineal interstitial prostate brachytherapy.
AB  - PURPOSE: To characterize the severity and time course of rectal toxicity
      following transperineal prostate brachytherapy using prospectively recorded data,
      and to determine factors associated with toxicity. METHODS AND MATERIALS: One
      hundred thirty-four patients with prostate cancer treated with transperineal
      brachytherapy from 1997 to 1999 had rectal toxicity data available for analysis.
      Patients with Gleason score (GS) > 6, prostate-specific antigen (PSA) > 6, or
      stage > T2a were treated initially with external beam radiation therapy followed
      by brachytherapy boost; patients with none of these features were treated with
      brachytherapy alone. Both iodine-125 and palladium-103 sources were used, and
      loaded according to a modified Quimby distribution. At each follow-up, toxicity
      was recorded according to a modified RTOG gastrointestinal scale. RESULTS: Thirty
      nine percent of patients experienced gastrointestinal toxicity, mostly Grade 1.
      Median duration of symptoms was 6 months. Two patients experienced Grade 3
      toxicity, both of whom had minimal symptoms until their 12-month follow-up. There
      was no Grade 4 or 5 toxicity. The addition of external beam radiation therapy (p
      = 0.003), higher clinical stage (p = 0.006), and Caucasian race (p = 0.01) were
      associated with increased incidence of toxicity. CONCLUSION: Most patients with
      rectal toxicity have very mild symptoms. There is a small risk of severe late
      toxicity. External beam radiation, higher stage, and race are associated with
      toxicity.

PMID- 12007948
TI  - An Internet-ready database for prospective randomized clinical trials of high
      dose-rate brachytherapy for adenocarcinoma of the prostate.
AB  - PURPOSE: To demonstrate a new interactive Internet-ready database for prospective
      clinical trials in high-dose-rate (HDR) brachytherapy for prostate cancer.
      METHODS AND MATERIALS: An Internet-ready database was created that allows common
      data acquisition and statistical analysis. Patient anonymity and confidentiality
      are preserved. These data forms include all common elements found from a survey
      of the databases. The forms allow the user to view patient data in a view-only or
      edit mode. Eight linked forms document patient data before and after receiving
      HDR therapy. The pretreatment forms are divided into four categories: staging,
      comorbid diseases, external beam radiotherapy data, and signs and symptoms. The
      posttreatment forms separate data by HDR implant information, HDR medications,
      posttreatment signs and symptoms, and follow-up data. The forms were tested for
      clinical usefulness. CONCLUSION: This Internet-based database enables the user to
      record and later analyze all relevant medical data and may become a reliable
      instrument for the follow-up of patients and evaluation of treatment results.

PMID- 12007949
TI  - Three-dimensional controlled interstitial hyperthermia combined with radiotherapy
      for locally advanced prostate carcinoma--a feasibility study.
AB  - PURPOSE: To perform a feasibility study of three-dimensional spatially controlled
      interstitial hyperthermia for locally advanced prostate cancer. METHODS AND
      MATERIALS: Twelve patients with prostate cancer (T3NxM0) were treated with
      conventional external beam radiotherapy and one interstitial hyperthermia
      treatment. Hyperthermia was delivered with the 27-MHz multielectrode current
      source (MECS) interstitial hyperthermia technique on an outpatient basis. Guided
      by transrectal ultrasonography, 12 catheters (range 7-16) were placed in the
      prostate through a template. Two electrodes per probe were inserted. Thermometry
      (average 100 sensors) was performed from within the probes for online temperature
      control. Additional thermometry was done in the prostate, rectum, urethra, and
      bladder. Reconstruction was done by sonography. Prostate perfusion was estimated
      from the thermal decay at the end of treatment. The full three-dimensional
      temperature distribution was calculated. RESULTS: No toxicities greater than
      Grade 2 were recorded. A learning curve for implantation, position verification,
      reconstruction, and temperature simulation was experienced. Perfusion was 47
      mL/100 g/min (range 30-65). The average measured temperature was T(90) (90% of
      the prostate reached a temperature of at least:) 39.9 degrees C and T(50) 44.1
      degrees C. The average calculated temperatures were lower: T(90), 39.4 degrees C
      and T(50), 41.8 degrees C, because the entire prostate was taken into account.
      The tumor temperatures were T(90), 40.7 degrees C and T(50), 43.0 degrees C. The
      bladder and rectal temperatures were below the safety limits. CONCLUSION:
      Multielectrode-current-source interstitial hyperthermia is technically feasible
      and well tolerated. It was not possible to achieve the goal temperature of 42-43
      degrees C because of high perfusion and implantation limitations.

PMID- 12007950
TI  - Prospective randomized trial of HDR brachytherapy as a sole modality in
      palliation of advanced esophageal carcinoma--an International Atomic Energy
      Agency study.
AB  - BACKGROUND: Previous studies from South Africa have established that fractionated
      high-dose-rate (HDR) brachytherapy gives the best results in terms of palliation
      and survival in advanced esophageal cancer. A multicenter, prospective randomized
      study was therefore conducted under the auspices of the International Atomic
      Energy Agency to evaluate two HDR regimens. METHODS AND MATERIALS: Surgically
      inoperable patients with histologically proven squamous cell cancer of the
      esophagus, tumor >5 cm in length on barium swallow and/or endoscopy, Karnofsky
      performance score >50, age 17-70 years, primary disease in the thoracic
      esophagus, no prior malignancy within the past 5 years, and any N or M status
      were included in the study. Exclusion criteria included cervical esophagus
      location, tumor extending <1 cm from the gastroesophageal junction,
      tracheoesophageal fistula, Karnofsky performance score <50, altered mental
      status, and extension to great vessels on CT. Patients were randomized to receive
      18 Gy in 3 fractions on alternate days (6 Gy per fraction, Group A) or 16 Gy in 2
      fractions on alternate days (8 Gy per fraction, Group B). The HDR dose was
      prescribed at 1 cm from the center of the source axis after dose optimization. A
      margin of 2 cm was included proximally and distally. The respective hospital and
      university committees gave approval for the study, and all patients provided
      informed consent. RESULTS: A total of 232 patients were entered into the study
      (112 in Group A and 120 in Group B). There was no difference between the groups
      for any of the prognostic variables. All patients were followed until death. The
      dysphagia-free survival for the whole group was 7.1 months (Group A, 7.8 months;
      Group B, 6.3 months; p >0.05). The overall survival was 7.9 months for the whole
      group (Group A, 9.1 months; Group B, 6.9 months; p >0.05). On univariate
      analysis, the presenting weight (p = 0.0083), gender (p = 0.0038), race (p =
      0.0105), the presenting dysphagia score (p = 0.0083), the treatment center (p =
      0.0029), and tumor grade (p = 0.0029) had an impact on the dysphagia-free
      survival, and gender (p = 0.0011) and performance score (p = 0.0060) had an
      impact on dysphagia-free survival on multivariate analysis. Only age had an
      impact on overall survival on both univariate (p = 0.0430) and multivariate (p =
      0.0331) analysis. The incidence of strictures (Group A, n = 12; Group B, n = 13;
      p >0.05) and fistulas (Group A, n = 11; Group B, n = 12; p >0.05) was similar in
      both groups. CONCLUSION: Fractionated HDR brachytherapy alone is an effective
      method of palliating advanced esophageal cancers, surpassing the results of any
      other modality of treatment presently available. Dose fractions of 6 Gy x 3 and 8
      Gy x 2 give similar results for dysphagia-free survival, overall survival,
      strictures, and fistulas and are equally effective in palliation of advanced
      esophageal cancer.

PMID- 12007951
TI  - Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5
      fluorouracil and cisplatin for T4 esophageal cancer with or without fistula.
AB  - PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a
      protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the
      safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997).
      METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal
      squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients,
      15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had
      evidence of fistula before treatment. Patients received a protracted infusion of
      5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10
      mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15
      fractions during 3 weeks. This schedule was repeated twice, with a 1-week split,
      for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3
      patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25
      patients who were treated with the full dose of CT-RT, 14 (56%) completed the two
      courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT
      but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete
      regression. Although Grade 3 hematologic toxicities were frequently noted, Grade
      4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2
      demonstrated the disappearance of the fistula after CT-RT. However, the worsening
      or development of an esophageal fistula was noted in 5 patients. The 2-year
      survival rate for patients with Stage III was 27%, and the median survival time
      for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively.
      CONCLUSION: Despite its significant toxicity for esophageal fistula, this
      concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin
      appears feasible and effective for T4 esophageal cancer with or without fistulas.

PMID- 12007952
TI  - Concurrent chemoradiotherapy with gemcitabine and cisplatin for pancreatic
      cancer: from the laboratory to the clinic.
AB  - PURPOSE: We have reported that gemcitabine and concurrent radiation is a
      promising therapy for patients with pancreatic cancer. We investigated whether
      the addition of cisplatin, which may increase the systemic efficacy of
      gemcitabine, would be synergistic with gemcitabine and/or radiation in human
      pancreatic cancer cell lines. METHODS AND MATERIALS: BxPc3 and Panc-1 human
      pancreatic cancer cells were treated with three different schedules before
      radiation: (A) a sequential incubation of gemcitabine for 2 h followed by
      cisplatin for 2 h, (B) gemcitabine for 2 h, followed by washout of drug,
      replenishment of media for a 24-h incubation, followed by cisplatin for 2 h, and
      (C) gemcitabine for 24 h with a concurrent incubation of cisplatin for the last 2
      h. Cells were assessed for clonogenic survival using a standard assay. Synergism
      was evaluated by the median effect analysis. RESULTS: The schedule shown to be
      maximally synergistic for both cell lines was the consecutive 2-h gemcitabine, 2
      h cisplatin exposure, particularly at surviving fractions of <0.5. Cisplatin did
      not produce radiosensitization nor did it affect gemcitabine-mediated
      radiosensitization. CONCLUSION: Cisplatin produces synergistic cytotoxicity with
      gemcitabine without compromising gemcitabine-mediated radiosensitization. On the
      basis of these laboratory and previous clinical observations, we have initiated a
      Phase I trial of cisplatin plus gemcitabine and radiotherapy in patients with
      unresectable pancreatic cancer.

PMID- 12007953
TI  - Length and quality of survival after external-beam radiotherapy with concurrent
      continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer.
AB  - PURPOSE: The purpose of this study was to evaluate whether external-beam
      radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion
      affects the length and quality of survival in patients with locally unresectable
      pancreatic cancer. METHODS: Thirty-one patients with histologically proven
      locally advanced and unresectable pancreatic cancer without distant metastases
      were evaluated in this prospective randomized trial. Sixteen patients received
      EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200
      mg/m(2)/day), whereas 15 patients received no chemoradiation. The length and
      quality of survival was analyzed and compared for the two groups. RESULTS: The
      median survival of 13.2 months and the 1-year survival rate of 53.3% in the
      chemoradiation group were significantly better than the respective 6.4 months and
      0% in the group without chemoradiotherapy (p = 0.0009). The average monthly
      Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation
      group, which was significantly higher than the 65.5 in the group without
      chemoradiotherapy (p < 0.0001). The number of hospital days per month of survival
      was significantly less in the chemoradiation than in the no-therapy group (12.3
      vs. 19.0 days, p < 0.05). In the chemoradiation group, 5 patients (31%) had a
      partial response, and 9 (56%) had radiologically stable disease at a median
      duration of 6.1 months. The patients who had chemoradiation had a lower rate of
      liver and peritoneal metastases than patients without chemoradiotherapy (31% vs.
      64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received
      pain relief that lasted a median of 5.2 months. CONCLUSIONS: EBRT with concurrent
      continuous 5-FU infusion increased the length and quality of survival as compared
      to no chemoradiotherapy and provided a definite palliative benefit for patients
      with unresectable pancreatic cancer.

PMID- 12007954
TI  - Dose-escalated total body irradiation and autologous stem cell transplantation
      for refractory hematologic malignancy.
AB  - PURPOSE: To evaluate the feasibility of dose escalation of total body irradiation
      (TBI) above the previously reported maximally tolerated dose, we have undertaken
      a Phase I-II trial of dose-escalated TBI with autologous peripheral blood stem
      cell transplantation (PBSCT) for chemotherapy-refractory lymphoma. METHODS AND
      MATERIALS: Nine lymphoma patients with primary refractory disease (PRD) or in
      resistant relapse (RR) received dose-escalated TBI and PBSCT. The three dose
      levels of fractionated TBI (200 cGy twice daily) were 1,600 cGy, 1,800 cGy, and
      2,000 cGy. Lung blocks were used to reduce the TBI transmission dose by 50%, and
      the chest wall dose was supplemented to the prescribed dose using electrons.
      Shielding of the kidneys was performed to keep the maximal renal dose at 1,600
      cGy. Three patients, two with non-Hodgkin's lymphoma (NHL) in RR and one with PRD
      Hodgkin's disease, received 1,600 cGy + PBSCT, three patients (two NHL in RR, one
      PRD) received 1,800 cGy + PBSCT, and three patients with NHL (two in RR, one PRD)
      received 2,000 cGy + PBSCT. RESULTS: Toxicities associated with this high-dose
      TBI regimen included reversible hepatic veno-occlusive disease in 1 patient,
      Grade 2 mucositis requiring narcotic analgesics in 8 patients, and neurologic
      toxicities consisting of a symmetrical sensory neuropathy (n = 4) and Lhermitte's
      syndrome (n = 1). Interstitial pneumonitis developed in 1 patient who received
      1,800 cGy after receiving recombinant alpha-interferon (with exacerbation after
      rechallenge with interferon). Six (66%) patients achieved a response. Four (44%)
      patients achieved complete responses, three of which were of a duration greater
      than 1 year, and 2 (22%) patients achieved a partial response. One patient
      remains disease-free more than 5 years posttransplant. Corticosteroid-induced
      gastritis and postoperative infection resulted in the death of 1 patient in
      complete response, 429 days posttransplant. CONCLUSION: TBI in a dose range 1,600
      2,000 cGy as preparative therapy for autologous PBSCT is feasible and has
      substantial activity in chemorefractory non-Hodgkin's and Hodgkin's lymphoma.

PMID- 12007955
TI  - Trends in, and predictors of, breast-conserving surgery and radiotherapy for
      breast cancer in Connecticut, 1988-1997.
AB  - PURPOSE: To describe the trends in, and predictors of, use of breast-conserving
      surgery (BCS) vs. mastectomy and use of post-BCS radiotherapy (RT), from 1988
      through 1997 among residents of Connecticut. METHODS AND MATERIALS: Data on
      surgical and RT procedures for 16,676 women diagnosed with early-stage (localized
      to the breast or with regional lymph node involvement) invasive breast cancer in
      1988-1997 were obtained from the population-based Connecticut Tumor Registry.
      RESULTS: Use of BCS (vs. mastectomy) increased over time and was lower for
      patients with nodal involvement or larger tumors. The absence of RT facilities at
      the hospital of first admission was negatively associated with BCS but not with
      post-BCS RT. Post-BCS RT was low among patients diagnosed at age 80+ years but
      increased over time only in this age group. CONCLUSION: Absence of RT at the
      hospital may be a deterrent to BCS. The temporal increase in post-BCS RT among
      patients diagnosed at age > or =80 years suggests changes in physicians'
      attitudes and/or patient preferences that require further study.

PMID- 12007956
TI  - Enhancement of radiation therapy by the novel vascular targeting agent ZD6126.
AB  - PURPOSE: The aim of this study was to evaluate the antitumor efficacy of the
      novel vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the
      rodent KHT sarcoma model, either alone or in combination with single- or
      fractionated-dose radiation therapy. METHODS: C3H/HeJ mice bearing i.m. KHT
      tumors were injected i.p. with ZD6126 doses ranging from 10 to 150 mg/kg. Tumors
      were irradiated locally in unanesthetized mice using a linear accelerator. Tumor
      response to ZD6126 administered alone or in combination with radiation was
      assessed by clonogenic cell survival assay or tumor growth delay. RESULTS:
      Treatment with ZD6126 led to a rapid tumor vascular shutdown as determined by
      Hoechst 33342 diffusion. Histologic evaluation showed morphologic damage of tumor
      cells within a few hours after drug exposure, followed by extensive central tumor
      necrosis and neoplastic cell death as a result of prolonged ischemia. When
      combined with radiation, a 150 mg/kg dose of ZD6126 reduced tumor cell survival
      10-500-fold compared with radiation alone. These enhancements in tumor cell
      killing could be achieved for ZD6126 given both before and after radiation
      exposure. Further, the shape of the cell survival curve observed after the
      combination therapy suggested that including ZD6126 in the treatment had a major
      effect on the radiation-resistant hypoxic cell subpopulation associated with this
      tumor. Finally, when given on a once-weekly basis in conjunction with
      fractionated radiotherapy, ZD6126 treatment was found to significantly increase
      the tumor response to daily 2.5 Gy fractions. CONCLUSION: The present results
      demonstrated that in the KHT sarcoma, ZD6126 caused rapid tumor vascular
      shutdown, induction of central tumor necrosis, tumor cell death secondary to
      ischemia, and enhancement of the antitumor effects of radiation therapy.

PMID- 12007957
TI  - A theoretical model for the effects of reduced hemoglobin-oxygen affinity on
      tumor oxygenation.
AB  - PURPOSE: To develop a theoretical model for oxygen delivery to tumors, and to use
      the model to simulate the effects of changing the affinity of hemoglobin for
      oxygen on tumor oxygenation. METHODS AND MATERIALS: Hemoglobin affinity is
      expressed in terms of P(50), the partial pressure of oxygen (Po(2)) at half
      saturation. Effects of changing P(50) on arterial Po(2) are predicted using an
      effective vessel approach to describe diffusive oxygen transport in the lungs,
      assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in
      oxygen content of blood as it flows through normal tissue before entering the
      tumor region is assumed fixed. The hypoxic fraction of the tumor region is
      predicted using a three-dimensional simulation of diffusion from a network of
      vessels whose geometry is derived from observations of tumor microvasculature in
      the rat. RESULTS: In air-breathing rats, predicted hypoxic fraction decreases
      with moderate increases in P(50), but increases with further increases of P(50),
      in agreement with previous experimental results. In rats breathing hyperoxic
      gases, and in humans breathing either normoxic or hyperoxic gases, increased
      P(50) is predicted to improve tumor oxygenation. CONCLUSIONS: The results support
      the administration of synthetic agents to increase P(50) during radiation
      treatment of tumors.

PMID- 12007958
TI  - Activation of the nuclear transcription factor kappaB (NFkappaB) and differential
      gene expression in U87 glioma cells after exposure to the cytoprotector
      amifostine.
AB  - PURPOSE: Amifostine has been approved as a therapy to decrease the incidence of
      moderate-to-severe xerostomia in patients undergoing postoperative radiation
      treatment for head-and-neck cancer. As a reducing agent capable of participating
      in intracellular reductive/oxidative processes, it has the potential to affect
      redox-sensitive transcription factors and gene expression. Amifostine's active
      free thiol WR-1065 was investigated to determine its effect on nuclear
      transcription factor kappaB (NFkappaB) activation and subsequent gene expression
      in U87 glioma cells. METHODS AND MATERIALS: The human glioma cell line U87 was
      grown to confluency and then exposed to WR-1065 at a concentration of 40 microM
      for times ranging from 30 min to 24 h. Changes in cell cycle were monitored by
      flow cytometry. The effect of WR-1065 on NFkappaB activation was determined by a
      gel shift assay. Changes in gene expression as a function of time of exposure to
      WR-1065 were determined by Northern blot and the Atlas Human cDNA Expression
      Array (Clontech, Palo Alto, CA). Changes in gene expression using the Atlas Array
      were verified by reverse transcriptase-polymerase chain reaction (RT-PCR) with
      gene-specific primers. RESULTS: Exposure of U87 cells to 40 microM WR-1065
      resulted in a marked activation of NFkappaB between 30 min and 1 h after
      treatment. Expression of MnSOD, an NFkappaB-responsive gene, was enhanced by over
      2-fold after 16 h of treatment and remained elevated at 24 h. During this period
      of time, no changes in cell cycle distribution were observed. To assess changes
      in the expression levels of NFkappaB-responsive genes as a function of WR-1065
      exposure, cDNA arrays containing 49 genes identified as having DNA-binding motifs
      for NFkappaB were used. Only five genes were found to be significantly affected
      at 1, 4, and/or 16 h of treatment. GST-3 and c-myc were repressed up to 2- and 4
      fold, respectively. The expression levels of IL-2Ra, RANTES, and c-myb, in
      contrast, were enhanced up to 14-, 3-, and 2-fold, respectively. The remaining
      genes having NFkappaB-responsive elements in their promoter regions were either
      not expressed (20 genes) or were not affected (24 genes) by exposure to WR-1065.
      CONCLUSIONS: The redox-sensitive transcription factor NFkappaB can be activated
      in U87 glioma cells by the active thiol form of the cytoprotector amifostine.
      Activation of NFkappaB by the antioxidant WR-1065 is accompanied by a reduced
      expression of the oncogene c-myc and an enhanced expression of the antioxidant
      gene MnSOD, a gene whose expression in tumor cells is relatively low, but when
      overexpressed has been correlated with a suppression of the malignant phenotype.
      Activation of NFkappaB by WR-1065, however, results in selective rather than
      global changes in the expression of genes containing NFkappaB-responsive
      elements.

PMID- 12007959
TI  - Analysis of heat-shock related gene expression in head-and-neck cancer using cDNA
      arrays.
AB  - PURPOSE: The aim of the present study was to identify genes regulated in the
      early response to heat-shock in human head-and-neck cancer cells using a cDNA
      array. METHODS AND MATERIALS: IMC-3 cells were heat-shocked at 44 degrees C for
      30 min, then incubated for 6 h. After 6 h incubation, mRNAs were extracted. Early
      gene expressions in IMC-3 cells were analyzed using a cDNA array after heat
      shock. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was
      performed to identify the expressions of mRNA for confirming features by cDNA
      array analysis in several other cell lines (KB, T3M-1, SCC-TF) as well as in IMC
      3 cells. RESULTS: Twenty-eight genes were found to be induced or upregulated by
      heat-shock in IMC-3 cells. These included genes involved in the apoptosis (e.g.,
      CC3, caspase10), tumor invasion (e.g., CC3, TIMP-3), cell cycle checkpoint
      control (e.g., DP-1, CDC25A), signal transduction (e.g., MEK1) as well as genes
      associated with heat stress (e.g., Hsp70B', Hsp40). Gene expressions of CC3 and
      MEK1 were recognized to be induced by heat-shock in pharyngeal cancer cells (KB,
      T3M-1) and lingual cancer cells (SCC-TF). CONCLUSION: The observed alteration in
      gene expression may play a role in various biochemical pathways of cancer cells
      exposed to heat-shock.

PMID- 12007960
TI  - Effect of gemcitabine on acute and late radiation toxicity of skin and underlying
      soft tissues to single-dose irradiation in a nude mice model.
AB  - PURPOSE: To investigate the influence of gemcitabine (GEM) on acute and late
      toxicity of radiotherapy (XRT) in an in vivo model of acute skin reactions and
      late fibrotic sequelae of skin and underlying soft tissues. METHODS AND
      MATERIALS: Single-fraction XRT was applied to the right hind leg of nude mice
      under ambient conditions. Single-dose GEM was applied i.p. (550 mg/kg body
      weight). In a first set of experiments, the influence of timing of chemotherapy
      relative to the onset of irradiation was investigated with GEM application 36,
      24, and 2 h before and 24 h subsequent to 40 Gy XRT. With a fixed interval
      between chemotherapy and XRT taken from these studies, the dose-response
      relationship was examined for XRT in the range of 20-65 Gy. Control mice were
      irradiated without GEM treatment. Using a scoring system, onset, duration, and
      extent of acute skin reactions were analyzed. Skin fibrosis was measured by
      intracutaneous ink-mark separation. Soft tissue fibrosis was assessed using the
      leg contracture assay. ED50 calculations were performed for extent of acute and
      late reactions. RESULTS: Timing of GEM application relative to XRT had no
      significant influence on acute skin reactions or on fibrotic changes. Onset,
      duration, and extent of acute skin toxicity, as well as skin and leg contracture,
      were not significantly modulated by GEM in the dose-response experiments with GEM
      applied 2 h before XRT. CONCLUSIONS: Acute and late toxicity of skin and
      underlying soft tissues is not significantly increased after single-fraction
      radiotherapy in combination with GEM in the nude mice model.

PMID- 12007961
TI  - Measurements and clinical consequences of prostate motion during a radiotherapy
      fraction.
AB  - PURPOSE: Here we study the magnitude of prostate motion during the delivery of a
      radiotherapy fraction. These motions have clinical consequences for on-line
      position verification and the choice of margins around the target volume. METHODS
      AND MATERIALS: We studied the motion of the prostate for 10 patients during 251
      radiotherapy treatment fractions by assessing the position of implanted gold
      markers. Gold markers of 1 mm diameter and 5 mm length were implanted in the
      prostate before the start of the radiotherapy. We obtained movies during each
      fraction using an a-Si flat-panel imager. The markers could be detected in
      separate frames using a marker extraction kernel. RESULTS: Marker displacements
      as large as 9.5 mm were detected in one fraction. The motion of the prostate is
      greatest in the caudal-cranial and the anterior-posterior directions. Within a
      time window of 2 to 3 min, deviations from the initial marker position, averaged
      over all patients, are 0.3 +/- 0.5 mm and -0.4 +/- 0.7 mm in the anterior
      posterior and caudal-cranial directions, respectively. CONCLUSIONS: It appeared
      that on average, the intrafraction prostate motions did not result in margins
      larger than 1 mm, provided that the position verification is performed at time
      intervals of 2 to 3 min. Only for some patients performing more frequent position
      verification or adding extra margins of 2 to 3 mm is required to account for
      intrafraction prostate motions.

PMID- 12007962
TI  - Dosimetric impact of the variation of the prostate volume and shape between
      pretreatment planning and treatment procedure.
AB  - PURPOSE: The goal of this study is to evaluate the dosimetric impact on a
      pretreatment planning of prostatic volume and shape variations occurring between
      the moment of the volume study (preplanning) and just before a transperineal
      permanent seed implant procedure. Such variations could be an obvious source of
      misplacement of the seeds relative to the prostate gland and organs at risk.
      Other sources of dosimetric uncertainties, such as misplacement due to the
      procedure itself or edema, are eliminated by looking at these variations before
      the implant procedure. METHODS AND MATERIALS: For 35 clinical cases, prostate
      contours were taken at preplanning time as well as in the operating room (OR)
      minutes before the procedure. Comparison of shape and volume between the two sets
      was made. The impact on V100 was evaluated by placing the seeds in their planned
      positions in the new volume (clinical situation) and also by performing a new
      plan with the second set of contours to simulate an intraoperative approach.
      RESULTS: The volume taken in the OR remained unchanged compared to the
      pretreatment planning volume in only 37% of the cases. While on average the dose
      coverage loss from pretreatment planning due to a combination of variations of
      volume and shape was small at 5.7%, a V100 degradation of up to 20.9% was
      observed in extreme cases. Even in cases in which no changes in volume were
      observed, changes in shape occurred and strongly affected implant dosimetry.
      CONCLUSIONS: Variations of volume and shape between pretreatment planning and the
      implant procedure can have a strong impact on the dosimetry if the planning and
      the implant procedure are not performed on the same day. This is an argument in
      favor of performing implant dosimetry in the OR.

PMID- 12007963
TI  - Intensity-modulated arc therapy simplified.
AB  - PURPOSE: We present a treatment planning strategy for intensity-modulated
      radiation therapy using gantry arcs with dynamic multileaf collimator, previously
      termed intensity-modulated arc therapy (IMAT). METHODS AND MATERIALS: The
      planning strategy is an extension of the photon bar arc and asymmetric arc
      techniques and is classified into three levels of complexity, with increasing
      number of gantry arcs. This principle allows us to generalize the analysis of the
      number of arcs required for intensity modulation for a given treatment site.
      Using a phantom, we illustrate how the current technique is more flexible than
      the photon bar arc technique. We then compare plans from our strategy with
      conventional three-dimensional conformal treatment plans for three sites:
      prostate (prostate plus seminal vesicles), posterior pharyngeal wall, and chest
      wall. RESULTS: Our strategy generates superior IMAT treatment plans compared to
      conventional three-dimensional conformal plans. The IMAT plans spare critical
      organs well, and the trade-off for simplicity is that the dose uniformity in the
      target volume may not rival that of true inverse treatment plans. CONCLUSIONS:
      The analyses presented in this paper give a better understanding of IMAT plans.
      Our strategy is easier to understand and more efficient in generating plans than
      inverse planning systems; our plans are also simpler to modify, and quality
      assurance is more intuitive.

PMID- 12007964
TI  - Advantages of using noncoplanar vs. axial beam arrangements when treating
      prostate cancer with intensity-modulated radiation therapy and the step-and-shoot
      delivery method.
AB  - PURPOSE: The focus of this work was to compare noncoplanar beam arrangements used
      for intensity-modulated radiation therapy (IMRT) step-and-shoot delivery to
      several axial beam arrangements used in the treatment of clinically localized
      prostate cancer. METHODS AND MATERIALS: A 5-field coronal crossfire beam
      arrangement was developed for IMRT with the objective of improving upon the
      rectal and bladder dose-volume histograms obtained using 5-, 7-, and 9-field
      axial beam arrangements. Additionally, a modified 7-field crossfire technique was
      developed yielding improved dose distributions. The average values of dose-volume
      histograms and the time for treatment delivery were evaluated for all plans for
      10 randomly chosen patients. RESULTS: Both crossfire IMRT techniques exhibited a
      15-25% decrease in dose to the hottest 10% and 20% of the rectum relative to all
      three axial IMRT techniques. The 5-field crossfire orientation yields slightly
      higher bladder doses when compared to the other techniques. In selected cases,
      the 7-field crossfire beam arrangement demonstrates decreased dose to the bladder
      when compared to all three axial techniques. A mean delivery time of 14 to 17.5
      min is noted for the noncoplanar arrangements after positioning and localization.
      CONCLUSIONS: A technique is described that allows additional normal tissue
      sparing during dose escalation to the prostate during IMRT delivery. This
      technique takes advantage of the spatial orientation between the prostate,
      rectum, and bladder. With patient setup and target localization time aside, a
      mean treatment time of 14 to 17.5 min allows the delivery of the crossfire plans
      to conform to standard treatment times.

PMID- 12007965
TI  - Secondary neutron dose during proton therapy using spot scanning.
AB  - PURPOSE: During proton radiotherapy, secondary neutrons are produced by nuclear
      interactions in the material in the beam line before and after entering the
      patient. The dose equivalent deposited by these neutrons is usually not
      considered in routine treatment planning. In this study, we estimated the neutron
      dose in patients from a spot scanning beam line by performing measurements and
      Monte Carlo simulations. METHODS AND MATERIALS: Measurements of the secondary
      neutron dose were performed during irradiation of a water phantom with 177-MeV
      protons using a Bonner sphere and CR39 etch detectors. Additionally, Monte Carlo
      simulations were performed using the FLUKA code. RESULTS: A comparison of our
      measurements with measurements taken at a beam line using the scatter foil
      technique shows a dose advantage of at least 10 for the spot scanning technique.
      In the region of the Bragg peak, the neutron dose equivalent can reach for a
      medium-sized target volume approximately 1% of the treatment dose. Neutron doses
      expected in healthy tissues of the patient (in the not-treated volume) are for
      large and medium target volumes, approximately 0.004 Sv and 0.002 Sv per
      treatment Gy, respectively. CONCLUSIONS: We conclude from the measurements and
      simulations that the dose deposited by secondary neutrons during proton
      radiotherapy using the spot scanning technique can be neglected in the treatment
      region. In the healthy tissue, the dose coming from neutrons (0.002 Sv per
      treatment Gy) is approximately a factor of two larger than during photon
      treatment (0.001 Sv). These contributions to the integral dose from neutrons are
      still very low when compared to the dose sparing that can be achieved by using a
      proton beam instead of photons.

PMID- 12007966
TI  - In regard to Sanghavi, Miranpuri, and Chappell et al.: radiosurgery for patients
      with brain metastases: a multi-institutional analysis stratified by the RTOG
      recursive partitioning analysis method. IJROBP 2001; 51:426-434.

PMID- 12007968
TI  - In regard to Salter et al., IJROBP 2001;51:555-562.

PMID- 12007970
TI  - Clinical trials for registration in the European Union: the EMEA 5-year
      experience in oncology.
AB  - The evaluation of quality, safety and efficacy of medicinal products by
      regulatory agencies is a necessary step for obtaining marketing authorisation in
      the European Union (EU). The objective of this paper is to outline some key
      aspects of the EU regulatory system relevant to the field of oncology. Regulatory
      standards in oncology and the experience with anti-neoplastic and endocrine
      therapy agents in the centralised EU review system are presented. Also, the most
      common pitfalls encountered with oncology applications that were rejected are
      illustrated. The review is based on the first 5 years (1995-1999) of operation of
      the European Agency for the Evaluation of Medicinal Products (EMEA). Nineteen out
      of 30 different oncology drugs submitted during this period were approved, based
      on the recommendations of the Committee for Proprietary Medicinal Products
      (CPMP), which is the main scientific body within the EMEA responsible for
      evaluating medicines for human use. Although, in general, randomised trials to
      test the benefit of the new drug are a prerequisite for approval, this series
      showed that in strictly defined situations, approval could be obtained based on
      non-randomised trials measuring surrogate endpoints, provided the applicant
      agreed to the completion of a further programme of studies. These situations were
      the majority in our series and the CPMP has produced a guideline in oncology to
      address these specific requirements. Eleven out of the 30 oncology applications
      did not establish a positive benefit/risk profile of the drug in the proposed
      therapeutic indication, and were therefore rejected. Failure generally occurred
      because applications were based on too small series of patients or relied on the
      results of exploratory analyses after pre-defined analyses had failed to produce
      the expected results or, particularly for diagnostic agents, due to the fact that
      the effect of the agent had been measured only in terms of endpoints that were of
      unclear relevance.

PMID- 12007971
TI  - Oncology drug development: United States Food and Drug Administration
      perspective.
AB  - The Food and Drug Administration (FDA) in the United States has multiple roles.
      The primary responsibilities for oncology drug products are the supervision of
      clinical research, the evaluation of marketing claims for new and previously
      approved drugs, the granting of exclusive marketing licenses for approved claims,
      and the monitoring of post-marketing activity for safety. Additional roles
      include providing incentives for developing products for rare diseases and
      children. The principles used for monitoring clinical studies are based on
      science, law and ethical guidelines. The principles used for evaluation of
      evidence to support marketing claims are based in science, law, regulation, and
      frequently the advice of a panel of external experts. Approved products should
      demonstrate patient benefit that is commensurate with the probable risks. The
      types of endpoints and their advantages and disadvantages for regulatory review
      are discussed. There are regulatory options available for conditional approval
      based on surrogate endpoints that are likely to predict patient benefit, a
      mechanism for reducing the time to review an application for indications with no
      known effective therapy, and procedures for providing access to patients for
      unapproved drugs.

PMID- 12007972
TI  - Oncology drug clinical development and approval in Japan: the role of the
      pharmaceuticals and medical devices evaluation center (PMDEC).
AB  - In 1996 the Japanese Diet amended the Pharmaceutical Affairs Law (PAL) and its
      related laws based on 1996 report of the ad-hoc Committee for Drug Safety
      Ensuring Measures. Between 1996 and 2000, the drug approval system in Japan
      underwent a series of radical reforms. We describe in this paper the current
      system for drug approval, discuss the post-approval reexamination and
      reevaluation system, conditions under which development and review may be
      expedited, and mechanisms for approval of off-label usage. Finally, we discuss
      the impact of the International Conference on Harmonization (ICH) agreement on
      drug development and review in Japan.

PMID- 12007973
TI  - Cancer clinical trials in Central and Eastern Europe: historical review.
AB  - Prospective clinical trials on cancer started in Central and Eastern Europe in
      the early 70s under the auspices of the Council of Mutual Economic Assistance
      (CMEA). The objective of the CMEA Chemotherapy Group was to conduct prospective
      phase III studies with particular focus on drugs developed in the member
      countries. The main organizational problems were insufficient contact with the
      Trial Center and the excessive formalism of the cooperation. In the mid-80s most
      of the clinical research was taken over by the new structure: the South and East
      European Oncology Group (SEEOG), later renamed the Central and East European
      Oncology Group (CEEOG). CEEOG is a drug-oriented group consisting currently of
      over 30 institutions from eight countries. Its major interests have included
      breast cancer, ovarian cancer, lung cancer and head and neck cancer. Most of the
      studies have been phase II trials carried out in cooperation with various
      international companies. Most recently another regional cooperative group has
      been created: the Central European Cooperative Oncology Group (CECOG), whose main
      objectives are to conduct phase III studies on new chemotherapy combinations.

PMID- 12007974
TI  - What is the proper threshold for platelet transfusion in patients with
      chemotherapy-induced thrombocytopenia?
AB  - Platelet transfusion therapy is an integral part of modern oncological practice
      and is used to treat hemorrhage associated with thrombocytopenia. More commonly,
      platelets are transfused to prevent hemorrhage in thrombocytopenic patients.
      Conventional wisdom has suggested a threshold for prophylactic transfusion of
      <20x10(9)/l. Many studies now support the safety of more conservative transfusion
      regimes that reduce patient exposure to donors and conserve precious resources,
      without an increase in risk of hemorrhage. This review presents the data to
      support the use of a prophylactic transfusion threshold of <10x10(9)/l in
      patients without risk factors for hemorrhage and who have ready access to
      emergent medical care.

PMID- 12007975
TI  - Activity of vinorelbine in gastrointestinal cancers.
AB  - Vinorelbine (VNR) is a semi-synthetic vinca alkaloid (5'nor-anhydro-vinblastine)
      that differs from other vinca alkaloids by a modification of the catharantine
      moiety of the molecule. VNR binds to tubulin and inhibits tubulin assembly and
      microtubule formation. It has less activity than other vinca alkaloids against
      axonal microtubules and this may account for its reduced neurotoxicity in
      clinical use. In gastrointestinal tumours, VNR did not show significant activity
      in advanced pancreatic adenocarcinomas. Two phase II studies in metastatic
      colorectal cancer resulted in conflicting results: no activity in first-line
      therapy on lung metastases, but encouraging results in 5-fluorouracil (5-FU)
      resistant metastases. Conversely, significant antitumoural effect in oesophageal
      squamous cell carcinoma has been demonstrated. The first study was performed in
      46 patients with metastatic disease. Six of 30 patients (20%) without prior
      chemotherapy achieved a partial response (95% confidence interval (CI), 8-39%).
      One of 16 (6%) with prior chemotherapy responded. Grade (gr) 3 or 4
      granulocytopaenia occurred in 59% of patients and peripheral neurotoxicity was
      minor (26% gr 1). These results were confirmed by another group. A phase I study
      was performed using VNR and concurrent radiation (64 Gy) in previously untreated
      patients with inoperable locally advanced oesophageal cancer ineligible for
      cisplatin-5-FU-based chemoradiation. Twenty-four patients entered the study. The
      maximal tolerated dose has been reached at 25 mg/m(2)/week, the dose-limiting
      toxicities being febrile neutropaenia and infection. Major objective tumour
      response was observed at each dose level except the first one. Recruitment is
      ongoing to confirm the recommended dose of VNR (20 mg/m(2)/week). A phase II
      study of a VNR-cisplatin combination in metastatic oesophageal squamous cell
      carcinoma was recently completed. Seventy-one eligible patients were included.
      Main toxicities were haematological (gr 3-4 granulocytopaenia, 41%), infection,
      vomiting and fatigue. The response rate was 37% (95% CI, 26-49%) with a median
      duration of response of 7.7 months. This 2-day regimen appears at least as active
      and less toxic than the standard 5-day 5-FU and cisplatin regimen.

PMID- 12007976
TI  - The evolving role of systemic therapy in high risk prostate cancer: strategies
      for cure in the 21st century.
AB  - High-risk prostate cancer is a heterogeneous group that includes patients with
      clinically locally advanced stage disease at diagnosis. Unlike overt locally
      advanced disease, prediction of risk in clinically localized disease at an
      individual patient level, is not always easy or accurate with present knowledge.
      Gleason score, pretreatment prostate specific antigen (PSA), and stage (capsular
      invasion, seminal vesicle and nodal involvement) are the universally recognized
      criteria used to define risk. Overall, this group of patients have a greater than
      50% risk of relapse. Historically, local treatment modalities with radical
      prostatectomy or radiation therapy constituted the mainstay of therapy in the
      majority of localized prostate cancer patients. However, the primary cause of
      failure and disease mortality stems from the development of systemic metastases.
      As we continue to witness stage migration towards earlier stage disease
      (presumably PSA related) and mortality reduction, devising better strategies for
      cure is a must. Recently completed randomized trials indicate a benefit from the
      use of hormonal therapy in patients with locally advanced prostate cancer treated
      with radiation therapy or node positive patients, post radical prostatectomy.
      While hormone-based combined modality trials have consistently shown improvements
      in local and systemic disease control, only two of these demonstrated
      improvements in overall survival. The palliative benefit of chemotherapy in
      hormone refractory disease and the promising response rates with newer agents has
      evoked interest in the use of chemotherapy in high-risk prostate cancer in the
      adjuvant and neoadjuvant settings. Several phase II and III trials are ongoing.
      Novel avenues of therapy such as tyrosine kinase inhibitors, gene therapy and
      angiogenesis inhibitors incorporated in a multimodality treatment strategy are
      likely to impact the course of this disease in the future.

PMID- 12007977
TI  - Supportive therapy of elderly cancer patients.
AB  - Elderly cancer patients often require supportive care due to the physiologic
      decline of organs and apparatus linked with the aging process per se, and for the
      effects of tumor or of anticancer treatments. Pain and nutritional deficits are
      some clinical aspects requiring supportive care. Lack of studies on these latter
      topics does not allow an in depth analysis of the problem. The present review
      deals with literature concerning pain and nutritional problems in the general
      cancer population with emphasis on aspects typical for elderly cancer subjects.
      Physiologic and cancer-related changes in body composition, physical function and
      cognitive capacity of the elderly are presented and, when appropriate, linked
      with pathogenetic factors of pain and malnutrition, as well as their treatment.
      Pain demographic data, pain intensity evaluation and currently available
      techniques to provide pain relief such as etiologic treatment, analgesic
      pharmacotherapy and invasive analgesic procedures, are extensively discussed.
      Causes and assessment of malnutrition as well as available nutritional approaches
      such as oral, enteral and parenteral nutrition are also debated.

PMID- 12007978
TI  - A head holder for magnetic resonance imaging that allows the stereotaxic
      alignment of spontaneously occurring intracranial mouse tumors.
AB  - The use of stereotaxic neurosurgery in rodent models of human disease requires
      the alignment of central nervous system (CNS) structures that can be identified
      and surgically approached with great accuracy. Current technologies make possible
      development of mouse lines with enhanced predispositions for the development of
      various diseases including tumors. When such tumors arise in the brain their
      location is unpredictable. Obtaining a biopsy or stereotaxically delivering local
      therapy requires that the site of such tumors be known with great precision. We
      devised a method to correlate images of mouse brain tumors acquired by magnetic
      resonance imaging (MRI) with stereotaxic coordinates that can be used for
      obtaining biopsies or administering local therapy. We constructed a head holder
      containing a pair of tubes filled with a substance that could be imaged by MR and
      which were separated by varying distances. This allowed the precise localization
      of the tumor in all three dimensions. The strategy we employed is adaptable to
      other imaging modalities and to other body sites.

PMID- 12007979
TI  - A simple method for focally delivering multiple drugs or ligands to cells.
AB  - A simple venturi-based "spritzer" device is described that is capable of
      repeatedly and rapidly delivering small volumes of different solutions to cells
      or tissues. This is particularly advantageous in situations when the appropriate
      ligand or drug is not known a priori and has to be determined "on the fly" during
      the limited lifetime of a preparation. The utility of the device is demonstrated
      for applying odorants to olfactory receptor neurons (ORNs).

PMID- 12007980
TI  - Optical imaging combined with targeted electrical recordings, microstimulation,
      or tracer injections.
AB  - To facilitate the combination of optical imaging with various electrode-based
      techniques, we have designed and produced a skull-mounting "sliding-top cranial
      window" and a removable "electrode positioner microdrive". These new devices were
      used to study sensory processing in chronic and acute experiments in the cerebral
      cortices of cats and monkeys. This assembly allows simultaneous optical imaging
      of intrinsic signals or voltage-sensitive dyes combined with extracellular
      recording (single and multiple unit recording and local field potential),
      intracellular recording, microstimulation, or targeted injection of tracers.
      After the functional architecture is determined by optical imaging, electrodes
      are targeted into a selected cortical site under full visual control, at a
      variety of penetration angles (30-90 degrees ), accessing a large cortical area.
      The device consists of three parts: (1) a skull-mounting chamber, (2) a sliding
      cap, and (3) a microdrive. The microdrive can easily be removed and the cranial
      window is then sealed and covered with a flat protective cover. For chronic
      experiments, this arrangement allows the animal to be handled over a long period
      while fitted with a sealed cranial window of minimal volume and weight, and with
      negligible risk of accidental damage or infection.

PMID- 12007981
TI  - Peptide substrates for ERK1/2: structure-function studies of serine 31 in
      tyrosine hydroxylase.
AB  - The first physiological substrate identified for the extracellular signal
      regulated protein kinases (ERKs) is serine 31 in tyrosine hydroxylase (TH), the
      rate-limiting enzyme in catecholamine biosynthesis. In the present studies,
      several synthetic peptides modeled after Ser31 in TH were evaluated as in vitro
      substrates for the ERKs. The phosphorylation of Ser31-containing peptides from
      type 1 human TH by activated, recombinant ERK2 was found to exhibit catalytic
      efficiencies (V(max)/K(m)) up to 4-fold higher than that of a synthetic myelin
      basic protein (MBP)-based peptide. Both types of peptides were also tested using
      extracts from PC12 cells (untreated or treated with nerve growth factor (NGF)).
      Although, the phosphorylation of the MBP peptide by extracts of PC12 cells was
      higher than that of the Ser31 peptide, the relative treatment-dependent increase
      was much greater for the Ser31 peptide and more closely mimicked the pattern of
      ERK phosphorylation, suggesting that the latter peptide may be a more specific
      substrate for the ERKs.

PMID- 12007982
TI  - Hidden Markov based autoregressive analysis of stationary and non-stationary
      electrophysiological signals for functional coupling studies.
AB  - In this paper, we apply multivariate autoregressive (MAR) models to problems of
      spectral estimation for stationary and non-stationary electrophysiological data.
      We describe how to estimate spectral matrices and approximate confidence limits
      from MAR coefficients, and for stationary data spectral results obtained from the
      MAR approach are compared with fast Fourier transform (FFT) estimates. The hidden
      Markov MAR (HMMAR) model is derived for spectral estimation of non-stationary
      data, and traditional model order selection problems such as the number of states
      to include in the hidden Markov model or the choice of MAR model order are
      addressed through the use of a Bayesian formalism.

PMID- 12007983
TI  - Improved hybrid clamp: resolution of tail currents following single action
      potentials.
AB  - Hybrid clamp protocols, in which a discontinuous single electrode voltage clamp
      (dSEVC) amplifier is switched from current to voltage clamp during the recording,
      are frequently used to investigate conductance changes after high frequency
      trains of action potentials. This technique is advantageous because it combines
      physiological stimulation of the cell with the possibility of analyzing the
      consecutive conductance changes quantitatively. In this study an improved hybrid
      clamp protocol, called dynamic hybrid clamp, is developed that enables the
      experimenter to study tail currents after single action potentials. The protocol
      employs real time action potential detection to assure precise timing of the mode
      switch and utilizes an external sample and hold amplifier to avoid voltage steps
      during the switch to voltage clamp. With the use of whole-cell patch clamp
      recordings and high switching frequencies (> or =25 kHz), dSEVC can easily be
      started with a minimal delay (<1.5 ms) after single action potentials and tail
      currents underlying afterhyperpolarisations (AHPs) and afterdepolarisations
      ensuing single spikes are clearly resolved. The dynamic hybrid clamp should also
      be useful for analysis of spontaneously occurring events such as intrinsic or
      population bursts.

PMID- 12007984
TI  - High-resolution iontophoresis for single-synapse stimulation.
AB  - We present a technique for stimulating post-synaptic receptors with
      neurotransmitter locally at a single synapse and with a concentration profile
      that is comparable to endogenous stimulation. We modify the technique of
      iontophoresis to use a 0.1 microm electrode tip for local stimulation, and we
      combine it with fast capacitance compensation to achieve high-speed application
      from a high-resistance tip. Ejection of fluorescent dye from the electrode shows
      that transmitter can be limited to the width of a single synapse and to a time
      scale similar to an endogenous event. The speed and localization of transmitter
      is confirmed by iontophoretically stimulating single labeled synapses in cultured
      hippocampal neurons held under voltage clamp. The amount of transmitter ejected
      is linear and reproducible over a physiologically relevant range, making this
      technique useful for examining receptor kinetics and receptor insertion/removal.
      The system should be capable of delivering any charged neurotransmitter, and we
      show examples using glutamate and GABA. The technique is also combined with
      computer-controlled manipulation to study the strength and plasticity of multiple
      synapses in real-time.

PMID- 12007985
TI  - Cell-type specific calcium responses in acute rat hippocampal slices.
AB  - The identification of glial cells and neurons in brain slices is often difficult
      or uncertain. We have previously found that cultured rat cerebellar astrocytes
      and presumed astrocytes in acute brain slices, but not neurons, respond with
      cytosolic Ca(2+) transients following Ca(2+) influx in low external K+
      concentrations (<1 mM; Cell Calcium 28 (2000) 247). We have now studied the
      possibility whether this Ca(2+) response can be employed to identify astrocytes
      during calcium imaging experiments. The Ca(2+) responses to low and high (50 mM)
      K+ were investigated in cells in culture and in hippocampal slices. In the
      stratum radiatum of hippocampal slices, S-100B-positive cells, presumed to be
      astrocytes, preferentially accumulated Fluo-4, while pyramidal neurons,
      identified by neuron-specific enolase, showed much lower Fluo-4 fluorescence,
      fixed with ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDAC). 81% of the cells
      with prominent Fluo-4 fluorescence showed responses to low K+, and 86% of these
      cells were S-100B-positive. Our results suggest that the responsiveness to low K+
      can help to identify astrocytes in acute brain slices.

PMID- 12007986
TI  - The use of a neural network system in the identification of motor unit
      characteristics from surface detected action potentials: a simulation study.
AB  - The surface detected motor unit action potential (MUAP) morphology depends on
      many physiological and anatomical characteristics of the contracting muscle that
      are not directly accessible to measurement. In this paper, a neural network based
      approach is proposed to estimate the motor unit (MU) parameters from a simulated
      single surface MUAP. We have developed an estimation system that is composed of
      the following stages: conduction velocity estimation, signal dimension reduction,
      MU parameters estimation, and number of MU fibres estimation. The parameter
      estimation stage employs four multilayer neural networks trained on simulated
      MUAPs corresponding to various ranges of MU parameters. In the estimation mode,
      this module produces four MU parameters sets. The selected set of the five muscle
      characteristics is that which minimises an error criterion on a signal
      reconstructed from the estimated parameters. The proposed system is tested with
      several simulated MUAPs signals with additive white noise in order to evaluate
      its performance. It is shown that the technique performs well when the signal to
      noise ratio is greater than 20 dB.

PMID- 12007987
TI  - Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the
      nasal cavity.
AB  - Drug transport from the nasal cavity to the brain has gained much interest in the
      last decade. In the present study, a model was developed to determine the uptake
      of drugs into the cerebrospinal fluid (CSF) after nasal delivery in rats. CSF
      samples were taken using a cisternal puncture method. In this method, a needle is
      advanced through the skin and muscles overlying the atlanto-occipital membrane
      into the cisterna magna, while the rat is fixed in a stereotaxic frame. This
      method appears to be superior over cannulation of the atlanto-occipital membrane
      for CSF sampling. The major advantages of the puncture method is the ability of
      serial and simultaneous CSF and blood sampling for over 2 h in the same rat. To
      obtain maximal drug absorption from the nasal cavity and uptake into CSF,
      different positions of the rat's head (upright-90 degrees, supine-90 degrees,
      supine-45 degrees and supine-70 degrees angles) were tested in nasal delivery
      studies using hydrocortisone (HC) as a model drug. Putting the rat in the supine
      90 degrees angle position increased the absorption of HC into plasma and CSF 2
      fold compared to the upright-90 degrees angle position. The supine-70 degrees
      angle position did not change the HC plasma and CSF levels compared to the supine
      90 degrees angle position. However, the supine-70 degrees angle position showed
      the fastest CSF sampling rate, enabling more accurate CSF sampling and therefore
      preferred for further studies. In conclusion, the cisternal puncture method using
      the supine-70 degrees and 90 degrees angle position is a suitable method to study
      drug transport from the nasal cavity into the CSF, with the ability of multiple
      CSF sampling.

PMID- 12007989
TI  - A first view of the structure of a type IA topoisomerase with bound DNA.
AB  - The first crystal structure of a type IA topoisomerase with bound DNA has been
      solved. The structure of Escherichia coli topoisomerase III provides key insights
      regarding the catalytic mechanism and the conformational changes that accompany
      DNA binding, and enhances our understanding of how topoisomerases control DNA
      topology in the cell.

PMID- 12007990
TI  - Toxins 'R' Us: more pharmacological tools from nature's superstore.
AB  - Conus venoms from marine cone snails continue to provide novel bioactive
      components. Two new classes of conopeptide specifically block alpha(1)
      adrenoceptors (rho-conopeptide) and noradrenaline transporters (chi
      conopeptides). Both classes are small peptides with two disulfide bonds. Rho
      conopeptide is structurally similar to alpha-conotoxins, which block nicotinic
      acetylcholine receptors, whereas the chi-conopeptides are unrelated to other
      conotoxins. Both types of conopeptides are non-competitive blockers. Because
      these peptides demonstrate greater selectivity than current drugs in clinical
      use, they could lead to the development of improved therapeutics.

PMID- 12007991
TI  - A role for APP in motility and transcription?
AB  - Recent studies suggest two novel roles for the amyloid precursor protein (APP):
      APP accelerates wound healing in MDCK cells and acts in a notch-like manner to
      activate transcription. Both of these putative functions are dependent on the
      interaction of APP with the APP-binding protein FE65. Future studies are required
      to understand the full implications of these new findings and to determine
      whether therapeutic strategies for Alzheimer's disease should take these putative
      functions into account.

PMID- 12007993
TI  - The role of the transferrin-transferrin-receptor system in drug delivery and
      targeting.
AB  - Exploration of the potential of site-specific and target-oriented drug delivery
      systems has gained interest recently. Indeed, the efficient cellular mechanism of
      transferrin uptake has been exploited for the delivery not only of anticancer
      drugs and proteins, but also of therapeutic genes into proliferating malignant
      cells that overexpress transferrin receptors. In particular, the transferrin
      receptor offers great promise in the delivery of therapeutic agents across the
      blood-brain barrier to the brain.

PMID- 12007998
TI  - Endothelium-dependent hyperpolarization as a remote anti-atherogenic mechanism.
AB  - Endothelial cell injury and the loss of cytoprotective mechanisms that involve
      nitric oxide, prostacyclin and endothelium-dependent hyperpolarization (EDH) are
      thought to underlie atherosclerosis, although how these mechanisms are anti
      atherogenic is unclear. This is particularly so because thrombus formation, one
      of the major initiators of the disease, usually occurs at discrete luminal sites;
      thus, only small numbers of endothelial cells can be recruited to initiate anti
      inflammatory responses. However, we, and others, have demonstrated that locally
      generated EDH spreads to endothelial cells and smooth muscle cells throughout a
      vessel to cause remote vasodilatation. In this article, we propose that, in
      addition to a widespread inhibitory signalling mechanism, EDH produced by the
      endothelium also initiates remote anti-inflammatory actions that prevent large
      blood vessels developing atherosclerosis.

PMID- 12007999
TI  - How much for a star? Elements for a rational choice of sample size in preclinical
      trials.
AB  - In the preclinical field, preliminary estimation of the number of experimental
      units to be included in a study is an important step in the setting up of the
      study. This estimation must be based on a dialogue between the experimenter and
      the statistician. This article, intended for both experimenters and
      statisticians, is designed to facilitate their dialogue by describing certain
      elements that are involved in the calculation of the optimal sample size in
      addition to the factors that influence their quantification. The proposed
      approach will result in better analysis of each experiment and, therefore, more
      globally, in rationalization of the use of experimental units.

PMID- 12008000
TI  - Functional versus chemical diversity: is biodiversity important for drug
      discovery?
AB  - Prospecting the full biodiversity of nature to find leads for new drugs is not
      necessary. Because finding leads is aimed at identifying biological activity,
      structure is of secondary importance. Furthermore, although natural chemical
      diversity might be unrivalled, functional diversity is bound to be considerably
      less. It is likely that many millions of chemically distinct molecules exist in
      nature but it is inconceivable that the number of different biological functions
      is near this number. This is corroborated by knowledge obtained from the genome
      sequences of an increasing number of species. It is unlikely that ligands for
      specific molecular targets are restricted to one species and even individual
      compounds are often found in more than one species. Important molecular
      mechanisms are likely to be ubiquitous and there are no a priori reasons to
      assume that some are restricted to, for example, tropical rainforests. Thus,
      there are no obvious advantages of "biodiversity prospecting", which will,
      possibly, endanger fragile ecosystems in the search for rare species.

PMID- 12008001
TI  - Analysis of exhaled breath condensate for monitoring airway inflammation.
AB  - Several inflammatory mediators have been identified in the exhaled breath
      condensate (EBC) that is formed by breathing through a cooling system. Analysis
      of EBC is a noninvasive method that allows repeat measurements of lung
      inflammation and is potentially useful for monitoring drug therapy.
      Characterization of the profiles of exhaled markers could help to discriminate
      between different inflammatory lung diseases; thus, EBC might be a novel,
      noninvasive approach to monitoring lung diseases. However, several methodological
      issues, such as standardization of sample collection and validation of analytical
      techniques, need to be addressed before this method can be applied clinically.
      Controlled studies are needed to establish the utility of EBC markers for guiding
      pharmacological treatment in inflammatory lung diseases.

PMID- 12008002
TI  - Assessing antidepressant activity in rodents: recent developments and future
      needs.
AB  - Animal models are indispensable tools in the search to identify new
      antidepressant drugs and to provide insights into the neuropathology that
      underlies the idiopathic disease state of depression. As new targets are
      developed, both serendipitously and through hypothesis-driven research, existing
      animal paradigms are being modified and new tests are being developed to detect
      antidepressant actions of compounds acting on a broad range of neural and genetic
      targets. This review focuses on recent findings regarding some of the most widely
      employed animal models used currently to predict antidepressant potential.
      Emphasis is placed on recent modifications to such paradigms that have increased
      their utility and reliability. Furthermore, some key issues that need to be
      addressed for future discovery of novel antidepressant agents are examined, and
      the available data on genetically altered mice that might lead to the discovery
      of novel targets for antidepressant action are collated.

PMID- 12008005
TI  - Improved detection of Sugarcane yellow leaf virus using a real-time fluorescent
      (TaqMan) RT-PCR assay.
AB  - Yellow leaf syndrome (YLS) of sugarcane has been associated with Sugarcane yellow
      leaf virus (ScYLV) and has been reported from most sugarcane growing countries
      around the world. As sugarcane is vegetatively propagated, it is important to use
      effective and sensitive detection methods to screen new propagating material.
      Virus detection in symptomatic tissue is currently achieved using enzyme linked
      immunosorbent assay (ELISA), tissue blot immunoassay (TBIA) or a conventional RT
      PCR based assay. This paper reports the development of an improved assay based on
      multiplex real-time fluorescent RT-PCR. The new assay is 100-fold more sensitive
      than conventional RT-PCR, and incorporates a novel 'RNA specific' internal
      positive control (based around the intron of the caffeic acid 3-o
      methyltransferase gene) to guard against false negative results. The paper also
      describes the comparison of eight RNA extraction methods for sugarcane tissue
      giving a number of alternatives for different laboratory situations. The
      sensitivity of this assay has allowed the detection of ScYLV in many samples that
      were thought to be healthy following conventional testing (RT-PCR, ELISA or
      TBIA). The detection of ScYLV using this TaqMan assay can be applied to the
      production of ScYLV-free plants and prevents its spread through the propagation
      material.

PMID- 12008006
TI  - Detection and species identification of four human herpesviruses using polymerase
      chain reaction coupled with restriction endonuclease analysis.
AB  - A polymerase chain reaction (PCR) based assay for detection and species
      identification of four human herpesviruses, including herpes simplex virus types
      1 and 2, Epstein-Barr virus, and cytomegalovirus was developed. The detection of
      the herpesviruses was achieved by seminested PCR with three primers targeting
      well-conserved regions within the DNA-polymerase gene. Virus species were
      identified by simple restriction enzyme digestion of the amplified products with
      TaqI or RsaI. In comparison with mono-specific nested PCR assays the tetra
      specific assay demonstrated similar specificity and sensitivity with reference
      and clinical samples. The tetra-specific assay is sensitive, cost effective, and
      can be used for examination of clinical samples of different origin.

PMID- 12008007
TI  - Optimisation of ISO 10705-1 on enumeration of F-specific bacteriophages.
AB  - During the European project 'Bacteriophages in bathing waters' (January 1996-June
      1999), research was carried out to optimise the method for detection and
      enumeration of F-specific (RNA) phages in water. It was evaluated whether further
      optimisation would be possible/needed for the procedure as described in the
      standard method of the International Organisation for Standardisation (ISO) 10705
      1. The research focused mainly on optimisation of the different steps for
      culturing the host strain WG49 Salmonella Typhimurium. It was concluded that all
      steps described in ISO 10705-1 are necessary and, if followed carefully, using a
      culture of host strain WG49 Salmonella Typhimurium of good quality, reliable
      results could be obtained for the enumeration of F-specific RNA phages.

PMID- 12008008
TI  - Evaluation of a new assay for hepatitis C virus genotyping and viral load
      determination in patients with chronic hepatitis C.
AB  - A new method for hepatitis C virus (HCV) genotyping that analyzes products
      generated with the HCV Amplicor Monitor Test has been developed. One hundred and
      sixty-two Japanese patients with chronic hepatitis C, including 59 patients with
      hemophilia, were tested for HCV genotypes and viral loads with this new test, and
      the results were compared with those of a genotyping assay that involved direct
      sequencing of the E1 region. HCV genotypes and viral loads were also compared
      between patients with and without hemophilia. There were no discrepancies between
      the two methods in determining genotypes 2a, 2b, and 3a. However, two patients
      infected with 1a were mistyped as 1b with the new assay. One patient not
      classified by this assay was genotype 4. Genotypes found in patients without
      hemophilia were 1b, 2a, and 2b. Genotypes 1a, 3a, and 4, which were minor
      variants in Japan, were detected only in patients with hemophilia. In addition, J
      type, which is a subtype of 1b that originated in Japan, was found at low
      frequency in hemophiliacs. Thus, the HCV genotypes in patients with hemophilia
      are likely to be of foreign origin. Overall, this new assay was accurate except
      for genotype 1a and 4, and allowed simultaneous assessment of genotype and viral
      load.

PMID- 12008009
TI  - Probable geographical grouping of PVY(N) and PVY(NTN) based on sequence variation
      in P1 and 5'-UTR of PVY genome and methods for differentiating North American
      PVY(NTN).
AB  - An increasing number of countries in recent years have reported the occurrence of
      potato tuber necrotic ringspot disease (PTNRD), caused by tobacco veinal necrosis
      strain of Potato virus Y (PVY(N)), belonging to the sub-group tuber necrosis
      (PVY(NTN)). Methods for the differentiation of PVY(NTN), based on primer
      sequences often detect isolates of European (EU) type but not the North American
      (NA) type. To resolve this problem, the nucleotide sequence of 5'-untranslated
      region (5'-UTR) and the P1 gene of 11 isolates of PVY(N) and PVY(NTN) from the
      European Union and North America was determined. Sequence comparison and
      phylogenetic analysis of 5'-UTR and P1 region indicated that PVY(N) isolates from
      the European Union and North America formed their own separate groups. Intra
      group sequence identity for all except one was over 98%, as opposed to the inter
      group identity of 90%. Additionally, the PVY(NTN) isolates from the European
      Union and North America clustered with their respective PVY(N) isolates. This
      indicates a possible evolution of PVY(NTN) isolates from the PVY(N) isolates of a
      geographical region. With this information of regional relationships of PVY(NTN)
      and PVY(N) isolates, two approaches were developed based on a competitive RT-PCR
      and a restriction pattern, for the differentiation of NA-PVY(NTN) from the local
      PVY(N) and from EU-PVY(NTN). Thus sequencing of the P1 gene and use of
      competitive RT-PCR approach could be applicable for determining the possible
      origin of new occurrences of PVY(NTN) from other geographical regions.

PMID- 12008010
TI  - A multivariate statistical analysis to follow the course of disease after
      infection of cats with different strains of the feline immunodeficiency virus
      (FIV).
AB  - A descriptive multivariate assay is described which is suitable to analyze
      results of a biological experiment with small sample size but high qualitative
      and quantitative complexity of variables. This type of assay allows evaluation of
      multiple variables observed in the course of an experimental virus infection
      (e.g. viremia, nucleic acid detection, antibody titers, clinical parameters, anti
      microbial treatments or vaccination) in a single graph. In our study, a multiple
      correspondence analysis (MCA) was used to correlate a total of 145 measurements
      from each of a dozen of variables measured in five groups of three cats infected
      by five isolates of feline immunodeficiency virus (FIV). Three groups of virus
      isolates with distinct virulence were defined and correlation between dynamics of
      lymphocyte subset counts and viral virulence was established. Comparison between
      the primary stages of illness and follow-up examinations were of prognostic value
      and are thus helpful for development and monitoring of therapeutic strategies.

PMID- 12008011
TI  - The fingerpad protocol to assess hygienic hand antiseptics against viruses.
AB  - Many types of viruses can be spread by the hands of caregivers and food handlers,
      and regular and proper decontamination of hands is crucial in interrupting such
      spread. Standardized methods to assess the virus-eliminating potential of
      handwash and handrub agents have not been available and this test method
      addresses this gap. Each fingerpad of an adult subject receives 10 microl of the
      test virus suspension and the inoculum allowed to dry. The contaminated area is
      then exposed to 1 ml of a control or test agent for the desired contact time and
      virus remaining on the fingerpad is eluted, and the eluates are titrated for
      infectious virus along with the required controls. The method can also allow the
      determination of further virus removal due to post-treatment rinsing of the
      fingerpads with water and/or their subsequent towel- or air-drying. Percent
      reductions in the amounts of infectious virus after treatment with the control
      and test agents are then determined. The method gives results that are comparable
      to those obtained using the whole-hand. The activities of all major classes of
      germicidal chemicals used in hygienic hand antiseptics have been tested against
      several enveloped and non-enveloped viruses of human origin.

PMID- 12008012
TI  - Reliability of rapid diagnostic tests for HIV variant infection.
AB  - The sensitivity of one ELISA method, six HIV-1/HIV-2 rapid screening tests, and
      one confirmatory test was evaluated in comparison with a third-generation EIA
      method (taken as the 'gold standard') and Western blot on well-characterized
      panels of sera. HIV diversity was represented by 50 HIV-1 group M subtype A to H,
      nine HIV-1 group O, 12 HIV-2, two HIV1+2 positive and six indeterminate Western
      blot profiles. Sensitivity during HIV-1 seroconversion was studied on 39 serial
      samples collected from six patients during early primary infection. Serial
      samples obtained from two primates during experimental primary SIV infection were
      used to mimic HIV-2 seroconversion samples. The sensitivity ranged from 100 to
      94.6% according to the test. During seroconversion, rapid tests became positive 2
      8 days later than the third-generation EIA. This reveals a major limitation of
      rapid tests, which are being recommended for use in developing countries. The
      lack of sensitivity seen during early HIV-1 seroconversion and/or limited
      specificity in some of the evaluated tests present serious limitations to their
      use in countries with high HIV incidence and variability. It is suggested that,
      as soon as possible, less sensitive rapid tests for blood bank screening should
      be abandoned in favor of highly sensitive rapid tests and/or more robust, more
      sensitive and cheaper ELISAs. These results stress the need for better screening
      tools and specific local evaluations.

PMID- 12008013
TI  - Preparation of purified, sterilized, and stable adenovirus vectors using albumin.
AB  - Cesium chloride ultracentrifugation combined with dialysis is a standard method
      for preparing a high titer of purified recombinant adenovirus. However, it was
      found that sterilization of the filter membrane after dialysis led to a complete
      loss of adenovirus activity. A virus pellet was visualized after centrifugation
      shortly and electron microscopy revealed an aggregation of recombinant virus
      within the filter membrane following dialysis with 10% (V/V) glycerol in
      phosphate buffered saline. The entrapment of aggregated adenovirus by the filter
      membrane explains why adenovirus activity is lost following sterilization. The
      addition of 1% albumin prevented viral aggregation and allowed the purified virus
      to retain its activity after filter sterilization. Furthermore, viral activity
      was retained within the 1% albumin solution for at least 1 week at 37 degrees C
      and for 2 weeks at 4 degrees C, whereas viral activity within the albumin-free
      solution was quickly lost.

PMID- 12008014
TI  - Development and assessment of a novel real-time PCR assay for quantitation of HBV
      DNA.
AB  - HBV DNA quantitation is used extensively for the monitoring of treatment of
      hepatitis B virus (HBV) infection. The aim of this study was to develop a highly
      sensitive and reproducible real-time PCR (RTD-PCR) assay for the quantitation of
      HBV DNA using the LightCycler system. The performance of this assay was assessed
      by analyzing serial dilutions of HBV genomic DNA of known concentration and the
      lower limit of detection was found to be 1 DNA copy/reaction. By using serial
      dilutions of plasmid standard, RTD-PCR was determined to quantify HBV DNA in a 10
      log10 dynamic range. RTD-PCR was found to be more sensitive than the commercially
      available tests such as the Quantiplex HBV DNA and the AMPLICOR HBV MONITOR
      assays. The median coefficient of variation of interexperimental variability was
      3.2%. The HBV DNA values obtained with RTD-PCR were highly correlated with assays
      available commercially. These findings suggest that our RTD-PCR assay combines
      high sensitivity and reproducibility for HBV DNA quantitation in an incomparable
      high dynamic range of quantitation.

PMID- 12008015
TI  - Detection of highly pathogenic and low pathogenic avian influenza subtype H5
      (Eurasian lineage) using NASBA.
AB  - Nucleic acid sequence-based amplification (NASBA) is a technique that allows the
      rapid amplification of specific regions of nucleic acid obtained from a diverse
      range of sources. It is especially suitable for amplifying RNA sequences. A NASBA
      technique has been developed that allows the detection of avian influenza A
      subtype H5 from allantoic fluid harvested from inoculated chick embryos. The
      amplified viral RNA is detected by electrochemiluminescence. The NASBA technique
      described below is rapid and specific for the identification of influenza A
      subtype H5 viruses of the Eurasian lineage. More importantly, it can be used to
      distinguish highly pathogenic and low pathogenic strains of the H5 subtype.

PMID- 12008016
TI  - Effects of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine on
      phencyclidine-induced behavior and expression of the immediate-early genes in the
      discrete brain regions of rats.
AB  - Because of the possible interaction between adenosine receptors and dopaminergic
      functions, the compound acting on the specific adenosine receptor subtype may be
      a candidate for novel antipsychotic drugs. To elucidate the antipsychotic
      potential of the selective adenosine A(1) receptor agonist N(6)
      cyclopentyladenosine (CPA), we examined herein the effects of CPA on
      phencyclidine (PCP)-induced behavior and expression of the immediate-early genes
      (IEGs), arc, c-fos and jun B, in the discrete brain regions of rats. PCP (7.5
      mg/kg, s.c.) increased locomotor activity and head weaving in rats and this
      effect was significantly attenuated by pretreatment with CPA (0.5 mg/kg, s.c.).
      PCP increased the mRNA levels of c-fos and jun B in the medial prefrontal cortex,
      nucleus accumbens and posterior cingulate cortex, while leaving the striatum and
      hippocampus unaffected. CPA pretreatment significantly attenuated the PCP-induced
      increase in c-fos mRNA levels in the medial prefrontal cortex and nucleus
      accumbens. CPA also significantly attenuated the PCP-induced arc expression in
      the medial prefrontal cortex and posterior cingulate cortex. When administered
      alone, CPA decreased the mRNA levels of all IEGs examined in the nucleus
      accumbens, but not in other brain regions. Based on the ability of CPA to inhibit
      PCP-induced hyperlocomotion and its interaction with neural systems in the medial
      prefrontal cortex, posterior cingulate cortex and nucleus accumbens, the present
      results provide further evidence for a significant antipsychotic effect of the
      adenosine A(1) receptor agonist.

PMID- 12008018
TI  - Analysis of uptake and release of newly synthesized acetylcholine in PC12 cells
      overexpressing the rat vesicular acetylcholine transporter (VAChT).
AB  - Rat VAChT cDNA was stably transfected into PC12 cells to generate cell clones
      overexpressing different quantities of VAChT protein. Membrane fractions prepared
      from one cell clone (#3) in which VAChT was highly expressed (as determined by
      Western blot and [(3)H]vesamicol binding analyses) accumulated approximately two
      and half times as much [(3)H]ACh during incubation as did membrane fractions
      prepared from control cells. Vesamicol inhibited this ATP-dependent uptake.
      Membrane fractions isolated from a second cell clone (#6), which contained
      considerably less VAChT protein than did clone #3, accumulated no more [(3)H]ACh
      than did control cells. We compared the accumulation of newly synthesized
      [(14)C]ACh by a particulate fraction prepared from clones #3 and #6 with
      untransfected cells when these cells were incubated with either labeled acetate
      or choline. The results indicated that particulate fractions of clones #3 and #6
      did not accumulate any more newly synthesized [(14)C]ACh than did the particulate
      fraction of untransfected cells. Furthermore, vesamicol reduced the filling of a
      particulate fraction of untransfected cells with newly synthesized ACh better
      than it reduced the refilling of a particulate fraction of VAChT-transfected
      cells. High K(+) depolarization did not release any more newly synthesized
      [(14)C]ACh from VAChT-transfected than it did from untransfected cells. In
      related studies, overexpression of VAChT in clone #3 induced a slight but
      significant increase in ChAT activity. Overall, our results indicate that an
      increase in the amount of VAChT protein associated with a particulate fraction of
      PC12 cells does not augment the amount of newly synthesized [(14)C]ACh acquired
      by that particulate fraction. However, it does reduce the effectiveness of
      vesamicol in blocking the filling of the particulate fraction with newly
      synthesized [(14)C]ACh. In summary, our results suggest that the vesicular
      release of ACh from PC12 cells is not regulated at the level of its uptake into
      synaptic vesicles.

PMID- 12008017
TI  - Isolation and structure of the mouse 14-3-3 eta chain gene and the distribution
      of 14-3-3 eta mRNA in the mouse brain.
AB  - 14-3-3 protein is a brain-specific protein discovered by Moore and Perez, but at
      present is thought to be a multifunctional protein. To clarify the brain-specific
      function of the protein, we intend constructing a 14-3-3 eta gene knock-out
      mouse. As the first step of this process, we isolated the mouse 14-3-3 eta chain
      gene and determined its structure. The mouse gene is about 10 kb long and
      composed of two exons separated by a long intron. The transcription start site
      was identified and the polyadenylation signals (AATAAA) were found in exon 2 of
      the mouse gene. In the 5'-upstream sequence, we found several cis elements
      including a CRE sequence, a TATA box-like sequence, and a C/EBP element.
      Furthermore, the distribution of 14-3-3 eta mRNA in the mouse brain was examined
      by in situ hybridization histochemistry. The highest signals were found in the
      Purkinje cells of the cerebellum, the pyramidal cells of the hippocampus and the
      olfactory bulb neurons of the adult mouse. Neuronal expression of 14-3-3 eta in
      these regions mRNA may generally increase during postnatal brain development. The
      distribution of protein kinase C gamma in the mouse brain was also examined by
      immunohistochemistry. From the distribution of 14-3-3 eta mRNA and protein kinase
      C gamma in the mouse brain, the involvement of these compounds in the induction
      and maintenance of LTP was discussed.

PMID- 12008019
TI  - Neurons expressing neuropeptide Y mRNA in the infundibular hypothalamus of
      Japanese quail are activated by fasting and co-express agouti-related protein
      mRNA.
AB  - The neural mechanisms involved in the compensatory hyperphagia exhibited by many
      vertebrate species after a fast are not fully understood but, in mammals, appear
      to involve nutritionally-sensitive neurons that co-express neuropeptide Y (NPY)
      and agouti-related protein (AGRP) in the infundibular hypothalamus. We
      investigated whether these neurons have been evolutionarily conserved in a non
      mammalian vertebrate, the Japanese quail. Birds exhibited compensatory
      hyperphagia 1 h after return of food following a 24-h fast. We addressed a
      potential regulatory role for NPY, first, by using in situ hybridisation (ISH) to
      map NPY gene expression in the hypothalamus. This revealed a strong signal in the
      infundibular nucleus (IN). Secondly, we quantified NPY gene expression in 24-h
      fasted birds compared to ad libitum fed controls using two independent methods.
      In whole hypothalamus, measured by ribonuclease protection assay, NPY mRNA
      increased 1.5-fold in fasted birds. A similar, 1.7-fold, increase was observed
      specifically in the IN when analysed by ISH. No differences in NPY expression
      between fed and fasted birds were observed in other brain regions. To determine
      whether NPY neurons in the avian IN co-express AGRP, we cloned a fragment of the
      quail AGRP gene and used it to localise AGRP mRNA by ISH. The gene was expressed
      exclusively in the hypothalamus, specifically in the IN, where its distribution
      matched that of NPY. Double-label ISH revealed that the majority of NPY neurons
      in the IN co-express AGRP mRNA. Collectively, these data indicate that this cell
      type has been neuroanatomically and functionally conserved during vertebrate
      evolution.

PMID- 12008020
TI  - Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant
      subunit that reduces calcium permeability.
AB  - We report the cloning and characterization of a novel NMDA receptor subunit cDNA,
      which encodes a predicted polypeptide of 1003 amino acids. Phylogenic analysis
      indicates that this new subunit is most closely related to NR3A. Therefore, we
      term it NR3B. Important functional domains of glutamate receptors, such as the
      ligand-binding domain, the channel pore, and the channel gate, are conserved in
      NR3B. NR3B mRNA was expressed highly in pons, midbrain, medulla, and the spinal
      cord, but at low levels in the forebrain and the cerebellum. Although NR3A mRNA
      expression decreases sharply after the second postnatal weeks, NR3B mRNA
      expression levels in whole brain were constant during postnatal development and
      into adult. Coimmunoprecipitation analysis showed that NR3B could form NMDA
      receptor complex with NR1a and NR2A subunits in heterologous cells. Although
      expression of NR3B alone did not reconstitute functional NMDA receptors,
      coexpression of NR3B reduced the Ca(2+) permeability of glutamate-induced
      currents in cells expressing NR1a and NR2A. These results indicate that NR3B is a
      dominant modulatory subunit that can modify the function of NMDA receptors. Since
      high Ca(2+) permeability of NMDA receptors is thought to be a key feature for
      NMDA receptors to play critical roles in neurodevelopment, synaptic plasticity,
      and neuronal death, NR3B may contribute to the regulation of these physiological
      and pathological processes.

PMID- 12008021
TI  - Different regulatory sequences are required for parvalbumin gene expression in
      skeletal muscles and neuronal cells of transgenic mice.
AB  - Parvalbumin (PV) is expressed in fast-twitch fibers in skeletal muscles and a
      subpopulation of inhibitory neurons in the CNS. We generated transgenic mice that
      expressed the human interleukin-2 receptor alpha-subunit-green fluorescent fusion
      protein (hIL-2R-GFP) using two types of PV transgene. One contained the hIL-2R
      GFP gene downstream of a 16.5-kb 5'-upstream PV genomic sequence (PV line). The
      other comprised the hIL-2R-GFP gene in bacterial artificial chromosome (BAC) with
      either a 180-kb (PA line) or 155-kb (PB line) insert encompassing the PV gene.
      Independent lines of all transgenic mice showed a faithful hIL-2R-GFP expression
      in fast-twitch muscle fibers. However, appreciable hIL-2R-GFP expression in the
      CNS occurred only in the PA transgenic lines. In one line of PA transgenic mice,
      hIL-2R-GFP was properly expressed in PV-containing neurons in the cerebellum,
      thalamic reticular nucleus, globus pallidus and cerebral cortex, though ectopic
      expression was observed in a particular subset of cerebellar astrocytes. Another
      line of PA transgenic mice showed a selective and mosaic expression of hIL-2R-GFP
      in PV-containing Purkinje, basket and stellate cells in the cerebellum. These
      results indicate that the 16.5-kb PV genomic sequence is sufficient for fiber
      type-selective transcription but additional regulatory sequences comprised in BAC
      DNA are required for proper expression in PV-containing neurons.

PMID- 12008022
TI  - Expression of mitochondrial tricarboxylate carrier TCC mRNA and protein in the
      rat brain.
AB  - The tricarboxylate carrier protein catalyzes an electroneutral exchange across
      the mitochondrial inner membrane of tricarboxylate, dicarboxylate or
      phosphoenolpyruvate. We examined expression and localization of mitochondrial
      tricarboxylate carrier TCC mRNA and protein in the rat brain. TCC mRNA was
      ubiquitously expressed in all rat tissues examined and was abundant in brain,
      liver and kidney. TCC protein as well as mRNA was widely expressed in brain, and
      the protein expression was strong in neuronal cells in the hippocampus, the
      olfactory bulb, the corpus mamillare and the cerebellum. Our results suggest that
      this tricarboxylate carrier protein may contribute to biosynthesis and
      bioenergetics in neuronal cells in brain.

PMID- 12008023
TI  - Estrogen regulation of gene expression in the brain: a possible mechanism
      altering the response to psychostimulants in female rats.
AB  - Acute behavioral responses to cocaine are more pronounced in female than in male
      rats. We have shown that 3 weeks of treatment with 17beta-estradiol (E(2))
      implants significantly enhanced the hyperactivity induced by cocaine in
      ovariectomized (OVX) rats. The ligand-bound estrogen receptor (ER) functions as a
      transcription factor to regulate the expression of E-responsive genes. Thus, we
      hypothesized that estrogen (E) modulates the behavioral response to cocaine via
      regulation of expression of components of dopamine (DA) and serotonin (5-HT)
      systems in mesolimbic nuclei important in the response to cocaine as well as the
      hypothalamus, a brain area known to be E-responsive. Adult female Sprague-Dawley
      rats were OVX; half of them then received E(2) implant (OVX+E) (n=8/group, two
      groups). Twenty-seven days later, brain tissue was collected to study E(2)
      effects on mRNA expression for DA D(1)-like (D(1)) and D(2)-like (D(2S), D(2L),
      D(3)) receptors, DA transporter (DAT), 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(2C)
      receptors, and 5-HT transporter (SERT) as well as ERalpha and ERbeta in amygdala,
      hypothalamus, nucleus accumbens, midbrain, and ventral tegmental area (VTA). We
      found that E(2) implants in OVX rats increased mRNA levels for D(1) receptor in
      hypothalamus, D(2L) receptor in midbrain, and D(3) receptor in VTA, and decreased
      D(3) receptor mRNA levels in midbrain relative to OVX controls. E(2) also
      increased 5-HT(2C) receptor mRNA levels in midbrain and hypothalamus. In
      addition, E(2) decreased mRNA levels for ERalpha in amygdala and hypothalamus and
      ERbeta in amygdala. The present study demonstrates that E can regulate mRNA
      expression for specific DA and 5-HT receptors in a region-specific manner and
      suggests that such modifications may contribute to the behavioral response to
      cocaine.

PMID- 12008024
TI  - Fatty acid amide hydrolase localization in the human central nervous system: an
      immunohistochemical study.
AB  - Recent discoveries have opened new fields for research on the biochemistry and
      pharmacology of cannabinoids. Among them, and most importantly, are the
      characterization and molecular cloning of central and peripheral cannabinoid
      receptors as well as the isolation of the first putative endogenous ligands that
      bind to them, anandamide and 2-arachidonylglycerol. The enzyme that degrades
      these so-called "endocannabinoids" is an integral membrane protein, fatty acid
      amide hydrolase. Its distribution and biochemistry in rat brain suggest that it
      plays a critical role in the regulation of the endocannabinoid system. However,
      few data exist regarding its distribution and mechanism of action in human
      tissues. To that end, we have studied its cellular distribution in the human
      central nervous system by immunohistochemistry. Using an affinity-purified
      antibody, we report that fatty acid amide hydrolase is localized to specific and
      well-delimited cell populations, including cortical pyramidal neurons,
      subcortical white matter astrocytes, striatal and striatoefferent projecting
      neurons, hypothalamic and midbrain nuclei, granular and molecular layers of the
      cerebellum, Purkinje neurons, dentate cerebellar nucleus, inferior olivary nuclei
      and others. This distribution resembles that of the central cannabinoid receptors
      as well as that of the enzyme distribution in the rat brain. In summary, the
      cellular localization of the degradative enzyme of the endogenous cannabinoid
      ligands in human central nervous system reveals its presence on both neuronal and
      glial elements and shows a significant overlapping with that of central
      cannabinoid receptors, mainly in areas related with motor control, confirming the
      notion that the endocannabinoid system plays a critical role in the control of
      movement.

PMID- 12008025
TI  - Alteration of nuclear glyceraldehyde-3-phosphate dehydrogenase structure in
      Huntington's disease fibroblasts.
AB  - The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may be
      involved in neuronal disease and in programmed cell death. Recent investigations
      indicate an in vitro physical association between GAPDH and huntingtin, the
      mutated protein in Huntington's disease (HD). Previous studies reveal the
      functional diversity of GAPDH as a membrane, cytoplasmic and nuclear protein.
      These activities are independent of its classical glycolytic function. Thus,
      huntingtin-GAPDH interactions could affect not only energy production but also
      result in pleiotropic effects involving various biochemical pathways in HD cells.
      We now report the identification of a nuclear high molecular weight (HMW) GAPDH
      species in Huntington's disease cells. In contrast, nuclei from age-matched
      control normal human cells did not contain the HMW GAPDH species. Further, this
      GAPDH structure was not observed in HD whole cell sonicates which are
      characterized by normal GAPDH activity. The disruption of intracellular structure
      is implicit in the preparation of whole cell sonicates. Therefore, these results
      suggest that the dissociation of the GAPDH protein from its high molecular weight
      structure results in the recovery of its function. These findings reveal a
      singular, new subcellular phenotype in HD cells. As such, they indicate an
      interrelationship between nuclear GAPDH function and huntingtin localization in
      this CAG expansion neuronal disease.

PMID- 12008026
TI  - Matrix metalloproteases and their inhibitors are produced by overlapping
      populations of activated astrocytes.
AB  - Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs)
      are involved in many cell migration phenomena and produced by many cell types,
      including neurons and glia. To assess their possible roles in brain injury and
      regeneration, we investigate their production by glial cells, after brain injury
      and in tissue culture, and we investigate whether they are capable of digesting
      known axon-inhibitory proteoglycans. To determine the action of MMPs, we
      incubated astrocyte conditioned medium with activated MMPs, then did western
      blots for several chondroitin sulphate proteoglycans. MMP-3 digested all five
      proteoglycans tested, whereas MMP-2 digested only two and MMP-9 none. To
      determine whether MMPs or TIMPs are produced by astrocytes in vitro, we tested
      both primary cultures and astrocyte cell lines by western blotting, and compared
      them with Schwann cells. All cultures produced at least some MMPs and TIMPs, with
      no obvious correlation with the ability of axons to grow on those cells. Both MMP
      9 and TIMP-3 were regulated by various cytokines. To determine which cells
      produce MMPs and TIMPs after brain injury, we made lesions of adult rat cortex,
      and did immunohistochemistry. MMP-2 was seen to be induced in activated
      astrocytes through the whole thickness of the cortex but not deeper, but MMP-3
      was not seen in the injured brain. TIMP-2 and TIMP-3 immunoreactivities were
      induced in activated astrocytes in deep cortex and the underlying white matter.
      In situ hybridisation confirmed induction of TIMP-2 in glia as well as neurons,
      but showed no expression of TIMP-4. These results show that both MMPs and TIMPs
      are produced by some astrocytes, but TIMP production is particularly strong,
      especially in deep cortex and white matter which is more inhibitory for axon
      regeneration. Conversely the MMPs produced may not be adequate to promote
      migration of cells and axons within the glial scar.

PMID- 12008027
TI  - Proceedings of the 11th Symposium on Signals and Signal Processing in the Immune
      System. Pecs, Hungary, 2-6 September 2001.

PMID- 12008028
TI  - Landing of immune receptors and signal proteins on lipid rafts: a safe way to be
      spatio-temporally coordinated?
AB  - In the past decade one of the cell biology's breakthroughs was discovery of
      membrane microdomains (rafts, caveolae) and recognition of their important in
      cellular signaling and protein traffic. In the present minireview a short
      comprehensive overview is given about physico-chemical, structural and functional
      properties of rafts. In addition to the classical immunochemical techniques the
      latest physcial and biophysical technologies that can be used to study these
      microdomains are also described briefly. The funcational significance of rafts in
      signaling of multichain immune recognition receptors (MIRRs), the IL-2R and ErbB
      family factor receptors is also discussed herein together with the still open
      questions and future prospects of the raft hypothesis.

PMID- 12008029
TI  - The role of SHIP in mast cell degranulation and IgE-induced mast cell survival.
AB  - Atopic disorders are on the increase in the Western world and are due, at least
      in part, to an overactive mast cell response. A better understanding of the
      intracellular signalling pathways that regulate both mast cell degranulation and
      the secretion of arachidonic acid metabolites and inflammatory cytokines could
      help in the treatment of these disorders. The src homology 2-containing inositol
      polyphosphate 5'-phosphatase, SHIP, has been shown to be a key 'gatekeeper' of
      mast cell degranulation. SHIP prevents degranulation from occuring when IgE alone
      binds to the high-affinity receptor for IgE (FcvarepsilonR1), SHIP restrains it
      when IgE-bound FcvarepsilonR1 are engaged by multivalent allergens, and SHIP
      inhibits it when an IgG against the same allergen co-clusters the inhibitory low
      affinity receptor for IgG (FcgammaRIIB) with the IgE receptor. SHIP acts as a
      negative regulator of degranulation by hydrolyzing phosphatidylinositol-3,4,5
      trisphosphate, a second messenger generated in activated cells by
      phosphatidylinositol 3-kinase. Our finding that binding of only IgE to the
      FcvarepsilonR1 of SHIP-deficient mast cells results in massive degranulation, led
      us to investigate the signalling pathways that are triggered in normal murine
      bone marrow-derived mast cells by monomeric IgE. We report here that monomeric
      IgE activates signalling pathways resulting in mast cell survival, without
      stimulating degranulation or proliferation. These studies demonstrate that mast
      cell sensitization by IgE is an active rather than a passive process.

PMID- 12008030
TI  - Clustering the mast cell function-associated antigen (MAFA) leads to tyrosine
      phosphorylation of p62Dok and SHIP and affects RBL-2H3 cell cycle.
AB  - The mast cell function-associated antigen (MAFA) is a type II membranal
      glycoprotein expressed by rat mast cells and basophils. MAFA clustering by its
      specific monoclonal antibody, (mAb) G63, efficiently inhibits the FcvarepsilonRI
      induced secretory response of mucosal-type mast cells of the RBL-2H3 line, as
      well as bone marrow-derived mast cells. Here we present results which suggest
      that MAFA has also a capacity of modulating the cell cycle of the RBL-2H3 line.
      We found that MAFA clustering, by mAb G63 or by its F(ab')2 fragments, reduces
      the cell proliferation rate. Cell cycle analysis by flow cytometry revealed that
      the number of cells in sub-G phase is considerably higher for cells on which MAFA
      was clustered. Results of biochemical experiments established that MAFA
      clustering leads to a marked increase in the transient tyrosine phosphorylation
      of the adaptor protein p62(Dok) and the inositol phosphatase SHIP. Concomitantly,
      their respective binding to RasGAP and Shc was increased. Furthermore, the GTP
      binding protein Sos1 was found to dissociate from Shc upon MAFA clustering,
      suggesting that SHIP and Sos1 compete for Shc binding. We therefore suggest that
      MAFA has also a role in regulating RBL-2H3 cell proliferation rate by inhibiting
      RasGTP formation in the Ras signaling pathway.

PMID- 12008031
TI  - Mucosal type mast cells express complement receptor type 2 (CD21).
AB  - Fragments of complement component C3 generated upon activation of the cascade
      play an important role in the induction and regulation of immune responses.
      Receptors interacting with various fragments of this versatile complement protein
      are expressed on a wide variety of cell types, including lymphocytes,
      macrophages, dendritic cells, follicular dendritic cells, granulocytes,
      erythrocytes and consequently, C3-products may influence several biological
      functions at different sites of the body, where complement activation occurs.
      Regarding the expression of various C3-receptors on mast cells, mainly rodent
      serosal type mastocytes have been investigated so far. It has been known for a
      long time that C3a triggers the release of mediators of immediate type
      hypersensitivity via binding to serosal-type cells. Complement receptor type 1
      (CR1/CD35) and type 2 (CR2/CD21) interacting with the larger activation products,
      such as C3b and C3d, have so far been shown on serosal type mast cells only. In
      this study, the expression of CR1/2 on mucosal type mast cells is demonstrated.
      Using mouse CR1/2 specific single chain antibodies and the natural ligand C3d in
      cytofluorimetric measurements, we show that the rat mucosal mast cell line RBL
      2H3 and mouse bone marrow-derived mast cells (BMMC) express CD21. RT-PCR
      experiments carried out with mouse CR1 and CR2 specific primers show CD21, but
      not CD35 specific products in BMMC. It is also demonstrated that, in contrast to
      serosal type mast cells, mucosal mastocytes do not express CD19. In an attempt to
      reveal the possible function of CR2 on mucosal type mast cells, the effect of
      receptor-clustering was tested regarding degranulation, Ca-response and IL-6
      production, but no CR2-mediated change was detected in any of these processes.

PMID- 12008032
TI  - In vitro and in vivo plasticity of Pax5-deficient pre-B I cells.
AB  - In mice deficient for the transcription factor Pax-5, B cell development is
      blocked at the pre-B I cell stage. Like wild type, Pax-5-/- pre-B I cells can be
      grown long-term in vitro in the presence of stromal cells and IL-7. However,
      unlike their wild type in vitro grown counterparts, Pax-5-/- pre-B I cells posses
      an extraordinary developmental plasticity showing hematopoeitic stem cell
      features such as multipotency and self renewing capacity. Here we review and
      discuss this in vitro and in vivo plasticity of Pax-5-/- pre-B I cells.

PMID- 12008033
TI  - BCR mediated signal transduction in immature and mature B cells.
AB  - Ligation of B cell receptors (BCR) on immature B cells may induce apoptosis,
      while in mature B cells it stimulates cell activation and growth. The signaling
      pathway regulating the differential functional response, death or survival of the
      B cell is not fully characterized. We have tested the intracellular signaling
      requirement of these processes using B cells isolated from the spleen of
      irradiated auto-reconstituted (transitional immature B cells) and untreated mice
      (mature B cells), respectively. We compared the BCR induced intracellular [Ca2+]
      transient, protein tyrosine phosphorylation and ERK phosphorylation, furthermore,
      the activation of Elk-1 and CREB transcription factors. The BCR induced rise of
      intracellular [Ca2+] did not significantly differ in the two populations, only a
      slight difference in the late phase of the response was observed. Immature B
      cells responded with a maximum tyrosine phosphorylation to a five times lower
      dose of anti-IgM compared to the mature population. Most importantly, we have
      found a significant difference in the tyrosine phosphorylation of the Gab family
      adaptor proteins, Gab1/2. In contrast to mature B cells, crosslinking of BCR on
      immature B cells did not induce tyrosine phosphorylation of Gab2, thus the Gab2
      organized signal amplification complex could not be produced. Furthermore, we
      detected a significant difference in the kinetics of BCR induced ERK, Elk-1 and
      CREB phosphorylation. In immature B cells, ERK was transiently phosphorylated,
      ceasing after 120 min, while in mature cells, ERK phosphorylation was sustained.
      Elk-1 and CREB activation was also transient in immature B cells, followed the
      kinetics of ERK phosphorylation. The lack of sustained Erk1/2 activation
      suppresses the transcription factors necessary for the proliferation signal.
      Since ERK is regulated by the phosphorylated Gab1/2, these data demonstrate that
      BCR triggered phosphorylation and signal amplification of Gab1/2 is a critical
      step in a life or death decision of B cells.

PMID- 12008034
TI  - The structure of Fc receptor/Ig complexes: considerations on stoichiometry and
      potential inhibitors.
AB  - Recently, Fc receptors for immunoglobulins moved further into the focus of pure
      and applied research as a role in the induction and development of autoimmune
      diseases and allergies is becoming more probable. Indeed by connecting the
      humoral with the cellular immune response FcRs possess an important role in the
      immune system in which the initial, crucial step is the binding of an
      immunoglobulin to the cell bound receptor. Thereafter a variety of effector
      functions depending on the cell and the receptor is triggered. This key event
      could recently be visualised with the solution of the crystal structure of a
      human Fc receptor in complex with its native ligand the Fc fragment of IgG1. In
      this paper the reasons for a 1:1 stoichiometry between Fc receptor and Fc
      Fragment and the medical applications of potential inhibitors of complex
      formation are highlighted.

PMID- 12008035
TI  - Interaction sites on human IgG-Fc for FcgammaR: current models.
AB  - Recombinant monoclonal antibodies have entered the clinic as effective in vivo
      therapeutic. A majority of the therapeutics antibodies employed are intact IgG
      molecules. IgG-antibody/antigen complexes can activate a wide range of biological
      responses that result in elimination and destruction of immune complexes.
      Principle ligands for the activation of clearance (inflammatory) mechanisms are
      the three types of cellular Fc receptors (FcgammaR) expressed on leucocytes. The
      effector functions activated by FcgammaR in vivo can be 'orchestrated', in part,
      through choice of the IgG subclass employed, however, there is potential to
      customize antibody therapeutics for optimal biological efficacy, in a particular
      clinical setting, i.e. with respect to the specific disease and the patient
      response. In order to engineer IgG antibodies and customize their abilities to
      activate FcgammaR it is necessary to elucidate the molecular specificity of their
      mutual interactions. This mini-review summarizes our current understanding of
      interactions of FcgammaRI, FcgammaRII and FcgammaRIII with human IgG antibodies.
      Particular emphasis is given to the influence of IgG-Fc glycosylation.

PMID- 12008036
TI  - On the mechanism of tolerance to the Rh D antigen mediated by passive anti-D (Rh
      D prophylaxis).
AB  - Anti-D prophylaxis is the most successful clinical application of antibody
      mediated immune suppression. Passive IgG anti-D is given to Rh D-negative women
      to prevent immunisation to foetal Rh D-positive red blood cells (RBC) and
      subsequent haemolytic disease of the newborn. Despite its widespread use and
      efficacy, the mechanism of action of this therapy is unproven. The known facts
      about the antigen, antibody response, dose of anti-D, RBC clearance and effects
      of the passive anti-D on subsequent primary and secondary immune responses are
      discussed in relation to recent information on ways by which immune responses may
      be suppressed. Most Rh D antigen sites on RBC are not bound by passive anti-D,
      and thus epitope masking (which may occur in experimental murine models using
      xenogeneic RBC) is not the reason why anti-D responses are prevented by
      administration of prophylactic anti-D. It is hypothesised that although clearance
      and destruction of the antigenic RBC may be a contributing factor in preventing
      immunisation, down-regulation of antigen-specific B cells through co-ligation of
      B cell receptors and inhibitory IgG Fc receptors must also occur.

PMID- 12008037
TI  - Superantigen concomitantly induces Th1 cytokine genes and the ability to shut off
      their expression on re-exposure to superantigen.
AB  - Superantigens, exemplified by staphylococcal enterotoxin B (SEB), are the
      strongest known inducers of a cellular immune response; they elicit the
      production of excessive amounts of Th1 cytokines, IL-2, IFN-gamma and TNF,
      leading to toxic shock. We show that increasing doses of SEB cause not only a
      greater induction but also a more rapid cessation of IL-2 gene expression.
      Remarkably, exposure of human PBMC to a second dose of SEB, even at
      concentrations 10- or 100-fold lower than the initial inducing dose and even
      within 2 h after the first exposure to SEB, resulted in an immediate and
      essentially complete shutoff of the induced IL-2 and IFN-gamma mRNA expression.
      The shutoff response was observed when primary induction of IL-2 and IFN-gamma
      gene expression was by SEB but not when it was by phytohemaggutinin-P. Signaling
      by a superantigen thus results not only in a vigorous induction of Th1 cytokine
      genes but concomitantly induces the ability to shut off their expression upon re
      exposure to superantigen. Without induction of this negative control mechanism,
      the cellular immune response to a superantigen would be even more pronounced.

PMID- 12008038
TI  - Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in
      gene expression profile of human hepatoma cells.
AB  - Interleukin-6 (IL-6) binds to a receptor complex consisting of an 80 kDa binding
      unit (IL-6R) and gp130 responsible for signal transduction. Due to alternative
      splicing and/or proteolytic digestion IL-6R occurs in soluble form (sIL-6R), as
      well. Soluble IL-6R is able to bind to gp130 expressing on nucleated cells, thus
      sIL-6R makes most cells responsive to IL-6. In this study we found that
      oncostatin M (OSM), an other gp130 dependent cytokine with proliferation
      inhibitory potential, increases the expression of both membrane-bound IL-6R and
      sIL-6R generated by alternative splicing in hepatic and mammary carcinoma cell
      lines. Furthermore, we studied the functional relevance of the presence and
      binding of soluble IL-6R to HepG2 cells. Using a cDNA expression array, mRNA
      levels of about 580 human genes were tested by differential display analysis. Our
      findings suggest, that elevation of surface density of IL-6R by attachment of sIL
      6R induces major modulation in gene expression profile of the hepatoma cells.
      Soluble IL-6R alone has minor effect, it rather decreases expression of some
      genes, while incubation with IL-6 and sIL-6R together induces major changes in
      the mRNA pattern of HepG2 cells. These data strongly suggest that presence and
      binding of soluble cytokine receptors are important elements of inter-cytokine
      cross talk and affects actual gene expression profile of responding cells.

PMID- 12008039
TI  - Mechanisms of TGF-beta signaling in regulation of cell growth and
      differentiation.
AB  - Transforming growth factor beta (TGF-beta) is a secreted protein that regulates
      proliferation, differentiation and death of various cell types. All immune cell
      lineages, including B, T and dendritic cells as well as macrophages, secrete TGF
      beta, which negatively regulates their proliferation, differentiation and
      activation by other cytokines. Thus, TGF-beta is a potent immunosuppressor and
      perturbation of TGF-beta signaling is linked to autoimmunity, inflammation and
      cancer. Regulation of cell proliferation and differentiation by TGF-beta is a
      topic of great basic and clinical importance. We summarize our work on the growth
      inhibitory pathway downstream of TGF-beta, which is triggered by receptor
      serine/threonine kinases at the cell surface and downstream effectors of the Smad
      family. Activated Smads regulate transcription of target genes, including cell
      cycle inhibitors such as p21, which mediate the anti-proliferative response and
      partially explain the tumor suppressive action of the TGF-beta pathway. We have
      described a molecular mechanism of regulation of the p21 gene by Smads and
      transcription factor Sp1. At late stages of tumor progression, TGF-beta promotes
      tumorigenesis via suppression of the immune system and changes in cell
      differentiation of epithelial tumor cells, a phenomenon termed epithelial to
      mesenchymal transdifferentiation (EMT). We review our work on the role of the
      Smad pathway in controlling EMT. In conclusion, the molecular pathways that
      describe the anti-proliferative and transdifferentiating effects of TGF-beta in
      epithelial cells have been uncovered to great molecular detail; a future
      challenge will be to test their generality in other systems, including the immune
      system.

PMID- 12008040
TI  - Does mosaicism of the plasma membrane at molecular and higher hierarchical levels
      in human lymphocytes carry information on the immediate history of cells?
AB  - A theoretical analysis of experimental data is presented in this mini-review on
      non-random homo- and hetero-associations of cell surface receptors, which can be
      recruited in the plasma membrane or at the surface of the rough endoplasmic
      reticulum during the protein synthesis. In the latter case, the likely genetic
      origin of these supramolecular formations is analyzed, contrasting this concept
      to the mobility of the cell surface proteins. A model is offered which, on the
      one hand, allows the mobility in a restricted way even among microdomain-confined
      receptor proteins through 'swapping partners'. On the other hand, the lack of
      mixing molecular components of protein clusters will be analyzed, when homo-and
      hetero-associations are studied through cell fusion experiments. The most
      frequently studied cell surface patterns have included lipid raft organized HLA
      class I and II, ICAM-1, tetraspan molecules, IL2 and IL15 and other receptors, as
      well. On the contrary coated pit-associated transferrin receptors would not mix
      with the above lipid raft associated receptor patterns, although transferrin
      receptor would readily oligomerize into homo-associates. The functional
      consequences of these superstructures are also analyzed. On the 30th anniversary
      of the Singer-Nicolson fluid mosaic membrane model one has to pay tribute to the
      authors, because of their deep insight emphasizing also the mosaicism of the
      membranes in general and that of the plasma membrane, in particular.

PMID- 12008041
TI  - Immunoregulation of CNS autoimmunity by helminth and mycobacterial infections.
AB  - The 'hygiene hypothesis' has been proposed to explain apparent increases in
      autoimmune disease and allergy in areas of the world with improved health care
      and sanitation. This hypothesis proposes that the lack of serious childhood
      infections impairs development of an appropriately educated immune response.
      Imbalance of Th1 and Th2 responses and lack of regulatory T-cell populations are
      two of many proposed potential mechanisms for immune failures such as
      autoimmunity and allergy. We summarize the literature evidence for the influence
      of infectious organisms on autoimmunity with focus on helminth and mycobacterial
      infections. We also demonstrate that Schistosoma mansoni ova pretreatment,
      Mycobacterium bovis (BCG) infection, and lyophilized Mycobacterium tuberculosis
      all modify the course of clinical disease in mice induced for experimental
      autoimmune encephalomyelitis (a mouse model for human multiple sclerosis (MS)).
      Our data supports the applicability of the hygiene hypothesis to CNS autoimmune
      disease.

PMID- 12008042
TI  - Possible co-regulation of genes associated with enhanced progression of mammary
      adenocarcinomas.
AB  - Tumor progression is a multistep process in which alterations in the expression
      of numerous gene products may give rise to highly malignant cellular variants. In
      the present study, we analyzed the differential expression of several genes in
      cellular variants of mammary adenocarcinomas with high or low malignancy
      potential, which originated in a common ancestor. To assess the generality of our
      findings, high and low malignancy variants were derived from two different
      mammary adenocarcinoma cell lines, namely DA3 and CSML cells. Of major importance
      is the fact that the differences between high- and low-malignancy variants
      observed in one system of mammary adenocarcinoma cells (DA3 cells) were
      identically reproduced in the other system of mammary adenocarcinoma cells (CSML
      cells). The high malignancy variants of tumors both DA3-high and CSML-high
      (previously called CSML-100), expressed higher levels of factors that induce
      monocyte migration than the low malignancy DA3-low and CSML-low (previously
      called CSML-0) variants. In addition, it was found that DA3-high and CSML-high
      cell variants expressed higher levels of monocyte chemoattractant protein-1 (MCP
      1), interleukin-6 (IL-6) and matrix metalloproteinases (MMPs) than the low
      malignancy variants (DA3-low and CSML-low). These results suggest that MCP-1, IL
      6 and MMPs potentially contribute to mammary adenocarcinoma progression and that
      their expression is regulated by a common pathway. The expression of MCP-1, IL-6
      and MMPs in both DA3-high and CSML-high cells was up-regulated by tumor necrosis
      factor alpha (TNFalpha). The fact that TNFalpha exerted similar effects on the
      expression of these three factors in both cell systems raises the possibility of
      a coordinated co-regulation of tumor-promoting factors.

PMID- 12008043
TI  - Heterogeneity of the DN4 (CD44-CD25-) subset of CD4-CD8- double negative
      thymocytes; dependence on CD3 signaling.
AB  - Recent studies have shown that apoptotic cell death associated with selection for
      thymocytes that express clonotypic TCRbeta or TCRgammadelta proteins takes place
      in the DN4 (CD44-CD25-) subset of CD4-CD8- double negative (DN) thymocytes. A
      detailed analysis of the DN4 subset is therefore of interest. Using intracellular
      (IC) staining for clonotypic TCR and CD3varepsilon proteins we find that DN4
      cells consist of five subpopulations:
      TCRbetaIC(high)/CD3varepsilonIC(high)/TCRgammadeltaIC-, TCRbetaI-C
      /CD3varepsilonIC(high)/TCRgammadeltaIC(+),
      TCRbetaIC(high)/CD3varepsilonIC(high)/TCRgammadeltaIC(+),
      TCRbetaIC(low)/CD3varepsilonIC(low)/TCRgammadeltaIC(-), and TCRbetaIC(
      )/CD3varepsilonIC(-)/TCRgammadeltaIC(-). Expression levels of IC
      TCRbeta/CD3varepsilon, and of Thy1.2, CD2, and CD69 at the cell surface suggest
      that the TCRbetaIC(low)/CD3varepsilonIC(low)/TCRgammadeltaIC(-) subset harbors
      the direct precursors of DP cells, and is critical for life/death decisions in
      early thymic selection. TCRbeta/CD3varepsilon downregulation is less pronounced
      in DN4 and DP cells of mice deficient for CD3zeta or for p56(lck), suggesting
      that the dynamics of TCR protein regulation in the DN4 subset is dependent on CD3
      signaling.

PMID- 12008044
TI  - Ligation of human CD4 interferes with antigen-induced activation of primary T
      cells.
AB  - The CD4 molecule functions to enhance T cell activation when it is co-aggregated
      with the T cell receptor for antigen (TCR) by MHC class II antigenic peptide
      complexes. However, independent ligation of CD4 has been shown to negatively
      effect signaling through the TCR in vitro. The interaction between the HIV-1
      envelope glycoprotein gp120 and CD4 is a central event in the pathogenesis of
      AIDS and may contribute to immune deficiency via both direct and indirect
      mechanisms, including lytic infection of T cells and induction of CD4 signaling
      events resulting in apoptosis and anergy. Analysis of the consequences of
      interactions between CD4 and gp120 have yielded contradictory results presumably
      because most of these studies have focused on T cell clones of questionable
      relevance to the in vivo target of the virus. Here, we analyzed the effects of
      CD4 ligation on freshly isolated cells of human CD4 transgenic mice, and show
      that huCD4 preligation, in the absence of human CXCR4, has an inhibitory effect
      on both early and late T cell activation events. CD4 signaling negatively
      regulates the response to antigen, as well as to anti-TCR mAb. In addition, we
      show here that this negative signal requires the cytoplasmic tail of CD4. These
      results suggest that in HIV infected patients the interaction of gp120 with CD4
      induces unresponsiveness of CD4+ T cells to subsequent activation by antigen.

PMID- 12008045
TI  - The X-linked lymphoproliferative disease gene product SAP is expressed in
      activated T and NK cells.
AB  - The unique manifestation of the inherited immunodeficiency, X-linked
      lymphoproliferative disease (XLP), is the impaired control of EBV infection. The
      gene, which carries mutations or is deleted in the patients, has been identified
      (Xq25). The encoded protein (SAP, 128 aa) contains a single SH2 domain and binds
      to signaling lymphocytic activation molecule (SLAM) and to other related surface
      molecules that are expressed on activated T, B and NK cells. SAP modifies signal
      transduction through its association with these molecules. Initially it was
      assumed that SAP acts passively by interfering and blocking active interactions
      involving other SH2 carrying molecules. We demonstrated that SAP protein is
      expressed in activated T and NK, but not in activated B cells. This finding is in
      line with the fact that in vitro performance of effector cells derived from XLP
      patients is impaired. However, it is still not known why the severe symptoms
      (fatal mononucleosis or malignant lymphoproliferation in the survivors of the
      primary infection) are elicited by EBV. We studied SAP expression in several
      Burkitt lymphoma (BL) derived lines. In contrast to normal B cells, certain lines
      expressed SAP. These were all type I cells in the Burkitt line nomenclature: they
      expressed only one of the EBV encoded proteins (EBNA-1) and their phenotype
      corresponded to resting B cells. Lymphoblastoid cell lines and type III BLs,
      whose phenotype resembled activated B cells and expressed all nine EBV encoded
      proteins, were devoid of SAP. The relationship between cell activation and SAP
      expression is reciprocal in T and B cells i.e. BL lines, activated T and NK cells
      express SAP, while BL blasts do not express SAP. This opposite relationship may
      be exploited for studies about the function of SAP.

PMID- 12008046
TI  - Receptor tyrosine phosphatase, CD45 binds galectin-1 but does not mediate its
      apoptotic signal in T cell lines.
AB  - Galectin-1 (Gal-1) is an endogenous mammalian S-type lectin with highly
      pleiotropic effect on different tissues. The viability of the lymphoid cells is
      reduced by gal-1 by triggering apoptosis, however, the mechanism of the gal-1
      induced apoptosis is still under investigation. The receptor tyrosine
      phosphatase, CD45, a heavily glycosylated cell surface molecule binds to gal-1
      with high affinity, however, its contribution to the gal-1 induced apoptosis is
      still controversial. In this study we show that galectin-1 binds to cells
      deficient for CD45, although CD45 is one of the galectin-1-binding cell surface
      proteins on T cells. Moreover, the CD45 deficient Jurkat variant, J45.01 responds
      readily with tyrosine phosphorylation and subsequent apoptosis to galectin-1
      treatment in a similar degree as its wild type counterpart, Jurkat does. These
      results strongly indicate that CD45 is not the receptor via gal-1 mediates the
      apoptotic signal into the cells as it was suggested in previous studies.

PMID- 12008047
TI  - Different proteins are phosphorylated under acidic environments in Jurkat cells.
AB  - In order to test the ability of immune cells to grow under acidic conditions,
      Jurkat cells were cultured in medium at pH 6.3. At this acidic pH, the cells
      required approximately 2 days per generation, while the generation time was
      approximately 1 day for cells grown in near neutral medium. Western blot analysis
      using anti-phosphotyrosine antibody (4G10) showed that protein phosphorylation
      was affected by external pH. For example, the level of a 66-kDa phosphoprotein
      increased dramatically in acidic medium, whereas the amount of a 34-kDa
      phosphoprotein decreased. These results suggest that Jurkat cells use different
      signal pathways under acidic environments.

PMID- 12008048
TI  - Effect of hyperglycemia on the basal cytosolic free calcium level, calcium signal
      and tyrosine-phosphorylation in human T-cells.
AB  - In this study, we investigated the effect of in vitro hyperglycemia on the
      function of human T-cells (Jurkat cells). Hyperglycemic conditions caused
      concentration-dependent elevation of basal cytosolic free calcium level and
      reduced calcium signal (activation capacity), either after ionomycin or
      monoclonal anti-CD3 antibody treatments. Similar changes were observed if cells
      were treated with the calcineurin inhibitor Cyclosporin-A. We found that tyrosine
      phosphorylation after anti-CD3 treatment was also impaired. High glucose
      concentrations in the tissue culture medium are also associated with increased
      non-enzymatic glycation of T-cell proteins. We propose that the increased
      glycation of proteins involved in calcium transport and/or intracellular signal
      transduction in T-cells accounts for the abnormal calcium sequestration and
      calcium mediated signal transduction.

PMID- 12008049
TI  - Enhanced resistancy of thioredoxin-transgenic mice against influenza virus
      induced pneumonia.
AB  - Thioredoxin (TRX) is a small redox-active protein with anti-oxidant effect and
      redox-regulating functions. Using TRX transgenic (Tg) mice in which human TRX is
      overexpressed systemically under the control of beta-actin promoter, the effects
      of influenza virus infection were examined in TRX Tg mice and wild type C57BL/6
      mice. (1) Median lethal dose (LD50) against influenza virus infection in wild
      type C57BL/6 mice was 10(-5.3) dilution, while that of TRX Tg mice was 10(-4.2)
      dilution. Thus, TRX Tg mice were more resistant against the virus infection than
      wild-type mice. (2) The body weights of wild-type mice 7 days after infection
      with a sublethal dose of the virus (10(-6) dilution) decreased significantly,
      whereas those of TRX Tg mice increased slightly. (3) Histopathology of the lung
      at 3 weeks after sublethal infection of influenza virus showed that severe
      alveolar or bronchiolar destruction was observed in wild-type mice, while mild
      viral pneumonia was seen in the TRX Tg mice. (4) Local (IgA) and systemic (IgG)
      antibody productions against influenza virus hemagglutinin in mice surviving 3
      weeks after infection were similar between wild-type and TRX Tg mice. These
      results indicate that overexpression of TRX in Tg mice suppresses the
      inflammatory overshoot of viral pneumonia caused by influenza virus infection,
      resulting in the reduction of mortality without affecting the host's systemic
      immune responses to the infection. TRX may play some important roles in
      regulating the inflammatory process in the primary host defense against
      infection.

PMID- 12008050
TI  - Novel substituted quinoxaline 1,4-dioxides with in vitro antimycobacterial and
      anticandida activity.
AB  - Thirty-six 6(7)-substituted-3-methyl- or 3-halogenomethyl-2-phenylthio
      phenylsulphonyl-chloro-quinoxaline 1,4-dioxides belonging to series 3-6 were
      synthesised and submitted to a preliminary in vitro evaluation for
      antimycobacterial, anticandida and antibacterial activities. Antitubercular
      screening showed a generally good activity of 3-methyl-2-phenylthioquinoxaline
      1,4-dioxides (3d,e,h-j) against Mycobacterium tuberculosis, and exhibited MIC
      between 0.39 and 0.78 microg mL(-1) (rifampicin MIC=0.25 microg mL(-1)), whereas
      in compounds 4d,e, 5a,b,d,e,l and 6b-e,j,l MIC ranged between 1.56 and 6.25
      microg mL(-1). Results of the antibacterial and anticandida screening showed that
      6e and 6l exhibited MIC=0.4 and 1.9 microg mL(-1), respectively, against Candida
      krusei (miconazole MIC=0.9 microg mL(-1)), and 4i, 5b,d, 6e, MIC=3.9 microg mL(
      1) against Candida glabrata (miconazole MIC=0.4 microg mL(-1)), while compounds
      3d,l, 5e,l, and 6b,d,e,l showed MIC=15.6 microg mL(-1) against Vibrio
      alginolyticus.

PMID- 12008051
TI  - Design, synthesis, DNA-binding and cytotoxicity evaluation of new potential
      combilexines.
AB  - Combilexines, compounds in which a DNA intercalator is linked to a minor groove
      binding component, interact with the DNA in a sequence specific manner to yield
      in most cases compounds with anticancer activity. A series of new compounds
      closely related to netropsin in which the two components were linked by an amide
      group was synthesised as potential combilexines. As some of these compounds
      showed cytotoxic activity in vitro, an attempt was made to rationalise their
      mechanism of action. The DNA binding characteristics of the carboxamides were
      evaluated by thermal denaturation experiments and by ethidium bromide
      displacement assay. Their ability to inhibit the topoisomerase I was also
      determined. It was concluded that the new compounds were only weak DNA ligands
      although able in some cases to inhibit topoisomerase I.

PMID- 12008052
TI  - CCK(2) receptor antagonists containing the conformationally constrained
      phenylalanine derivatives, including the new amino acid Xic.
AB  - The conformationally constrained analogues of phenylalanine,
      tetrahydroisoquinoline-3-carboxylic acid (Tic), Sic, Hic and Nic, and the new
      amino acid Xic have been incorporated into a potent and highly selective
      cholecystokinin-2 (CCK(2)) receptor antagonist (2) in place of the phenylalanine
      residue, producing compounds 15a-e. High selectivities for CCK(2) over CCK(1)
      were observed for compounds 15a-e. The in vitro profile of the analogue
      containing the Nic residue (15d) was identical to that of compound 2, whereas the
      alternative conformational constraints resulted in a significant loss of
      affinity. The apparent advantage of Nic in the context of these CCK(2) ligands
      was subsequently demonstrated to be statistically significant.

PMID- 12008053
TI  - (E)-[2-(4-Methylsulphonylphenyl)-1-cyclopentenyl-1
      methyliden](arylmethyloxy)amines. Methyleneaminoxymethyl (MAOM) analogues of
      diarylcyclopentenyl cyclooxygenase-2 inhibitors: synthesis and biological
      properties.
AB  - The (E)-[2-(4-Methylsulphonylphenyl)-1-cyclopentenyl-1
      methyliden](methyloxy)amine (5) and (arylmethyloxy)amines (6-12) were designed in
      order to verify the effects on the biological properties of the substitution of
      an aryl of selective diarylcyclopentenyl cyclooxygenase-2 (COX-2) inhibitors of
      type 3 with a methyleneaminoxymethyl moiety (MAOMM). Compounds 5-12 were tested
      in vitro for their inhibitory activity towards COX-1 and COX-2 by measuring
      prostaglandin E2 (PGE2) production in U937 cell lines and activated J774.2
      macrophages, respectively. The compound with the highest in vitro activity
      towards COX-2 (9) was also assayed in vivo for its antiinflammatory activity by
      means of the carrageenan-induced paw edema test in rats. Some of the new
      compounds showed an appreciable in vitro COX-2 inhibitory activity, with IC(50)
      values in the microM (6,7,9,10,11) range. Compound 9 also exhibited an
      appreciable in vivo activity (29% inhibition at a dose of 30 mg kg(-1)) when
      administered intraperitoneally. The structural parameters of 9 were determined by
      X-ray crystallographic analysis.

PMID- 12008054
TI  - A comparative study of artificial membrane permeability assay for high throughput
      profiling of drug absorption potential.
AB  - Artificial membrane permeability measurement is a potentially high throughput and
      low cost alternative for in vitro assessment of drug absorption potential. It
      will be an ideal screening/profiling tool in the lead generation program of drug
      discovery research if it is proven to be generally applicable for classifying
      drug absorption potential and is advantageous over other in vitro or in silico
      methods. This study provides an in-depth evaluation of the method in close
      comparison to Caco-2, LogD, LogP, polar surface area (PSA), and quantitative
      structure-property relationship (QSPR) predictions using a large and diverse
      compound set. It showed that the accuracy of using artificial membrane
      permeability in assessing drug absorption is comparable to Caco-2, but
      significantly better than LogP, LogD, PSA, and QSPR predictions. This study also
      explored the artificial membrane composition by adopting a hydrophilic filter
      membrane for artificial membrane (lecithin-dodecane) support. The use of
      hydrophilic filter membrane increased the rate of permeation significantly and
      reduced the transport time to 2 h or less as compared with over 10 h when a
      hydrophobic filter membrane is used.

PMID- 12008055
TI  - Synthesis and preliminary evaluation of benzimidazole derivatives as
      antimicrobial agents.
AB  - A series of 2-alkylsulphanylbenzimidazoles was synthesised and the compounds were
      evaluated for their in vitro antimicrobial activity. The structures of the
      compounds were confirmed by 1H-NMR and IR data, and their purity by elemental
      analysis. Antimycobacterial activities against Mycobacterium tuberculosis and non
      tuberculous mycobacteria as well as antifungal activities against Candida
      albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon
      beigelii, Trichophyton mentagrophytes and Aspergillus fumigatus were expressed as
      the corresponding MIC values. The substances exhibited appreciable
      antimycobacterial activity, in particular, against non-tuberculous mycobacteria.
      The activity of the most active compound in the set, 3,5-dinitro derivative 4t,
      exceeded that of the standard isoniazide against M. kansasii and M. avium. The
      antifungal activities of the compounds were relatively low. A weak antifungal
      effect was observed against the dermatophyte Trichophyton mentagrophytes. None of
      the compounds showed significant inhibitory activity against yeasts.

PMID- 12008056
TI  - Synthesis and bronchodilatory activity of some nitrogen bridgehead compounds.
AB  - A series of tricyclic nitrogen bridgehead compounds 7-22 have been synthesised
      and evaluated for their in vitro bronchodilatory activity using isolated guinea
      pig tracheal chain, precontracted with acetylcholine. The relaxant effect of
      2,3,4,5-tetrahydroazepino[2,1-b]-8,9-dimethoxyquinazolin-11(1H)-one (7) (DPJ-386)
      was greater than that of theophylline, aminophylline and quinazoline derivative
      3, which lacks methoxy groups at positions 8 and 9. Various nitrogen containing
      functionalities such as benzylamino, acetamido, benzamido and phthalimido were
      also introduced at 9 position of 3. This resulted in loss of relaxation activity
      in precontracted guinea pig tracheal chain. These results show that the better
      relaxation property possessed by compound 7 hydrochloride is due to methoxy
      groups at 8 and 9 positions.

PMID- 12008057
TI  - Mannich bases of 3H-pyrrolo[3,2-f]quinoline having vasorelaxing activity.
AB  - Mannich bases obtained by aminoalkylation of 3H-pyrrolo[3,2-f]quinoline were
      designed and prepared as potential vasorelaxing agents. Compounds Ia-Va were
      characterised by IR, 1H-NMR, mass spectral data and elemental analysis; IIb,c
      Vb,c were also confirmed by 1H-NMR spectra of reaction mixtures. To estimate
      their vascular activity, prototypes 1-(N,N-dimethylaminomethyl)- (Ia) and 1-(4
      phenyl-piperazin-1-ylmethyl)- (IVa) 3H-pyrrolo[3,2-f]quinoline derivatives were
      studied in rat-tail arteries. In tissues precontracted with 0.5 microM 5
      hydroxytryptamine (5-HT), 3 microM phenylephrine or 80 mM KCl, Ia and IVa showed
      endothelium-independent relaxing action. In a preliminary study on the cellular
      mechanisms of Ia, the influence of propranolol, a beta-receptor antagonist, and
      ketanserin, a 5-HT(2A)-receptor antagonist, was checked. In the presence of
      phenylephrine, the vasorelaxing effect of Ia was not affected by these
      inhibitors.

PMID- 12008058
TI  - Dimers from dechlorinated rebeccamycin: synthesis, interaction with DNA, and
      antiproliferative activities.
AB  - In the course of structure-activity relationships on rebeccamycin analogues, two
      dimers of dechlorinated rebeccamycin were synthesised with the aim to improve the
      interaction with DNA and in vitro antiproliferative activities. The synthesis of
      two dimeric compounds obtained by joining two molecules of dechlorinated
      rebeccamycin via the imide nitrogen is described. Melting temperature and DNase I
      footprinting studies were performed to investigate their interaction with DNA.
      Four tumour cell lines, murine L1210 leukaemia, human HT29 colon carcinoma, A549
      non-small cell lung carcinoma and K-562 leukaemia, were used to evaluate the
      cytotoxicity of the drugs. Their effects on the cell cycle of L1210 cells were
      also investigated.

PMID- 12008069
TI  - Expression of AMPA/kainate receptors during development of chick embryo retina
      cells: in vitro versus in vivo studies.
AB  - The activity and the subunit expression of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA)/kainate ionotropic glutamate receptors were
      studied in retina cells developing in chick embryos and in retina cells cultured
      as retinospheroids, at the same stages of development. In the retinospheroids,
      the activity of the AMPA/kainate receptors was monitored by following the changes
      in the intracellular free calcium concentration ([Ca(2+)](i)), in response to
      AMPA, kainate or to L-glutamate, and the expression of the receptor subunits
      GluR1, GluR2/3, GluR4 and GluR6/7 was determined in the retinospheroids and in
      chick retinas by immunodetection using polyclonal antibodies. The changes in
      [Ca(2+)](i) in response to 400 microM kainate increased from 5h in vitro to 3
      days, and remained constant until day 14, whereas the [Ca(2+)](i) in response to
      500 microM L-glutamate or 400 microM AMPA increased from 5h in vitro to 3 days,
      and thereafter decreased slightly until day 14. The [Ca(2+)](i) responses to
      kainate are mainly due to AMPA receptor stimulation, since the signals were
      abolished by LY303070, the AMPA receptor antagonist, and were not affected by MK
      801, the NMDA receptor antagonist. In retinospheroids, the levels of expression
      of GluR1 subunit increased from 5h in vitro until day 7, then decreased until day
      14. The levels of expression of GluR2/3 and GluR4 subunits increased from 5h in
      vitro until day 10, and remained constant until day 14. The levels of kainate
      receptor subunits GluR6/7 increased from 5h in vitro until day 3, and thereafter
      decreased slightly until day 14. In the retinas, the expression of GluR1 and
      GluR6/7 subunits increased from day 8 until day 15, and then decreased until day
      22 (post-natal 1). The subunits GluR2/3 and GluR4 increased from day 8 until day
      18, and remained constant until day 22. The results suggest that AMPA/kainate
      receptors are expressed at early embryonic stages, although at low levels and
      before synapse formation (E12). However, the AMPA receptors are not completely
      functional at the first stage studied since they do not respond to the agonist
      AMPA. Also, the patterns of AMPA/kainate receptor subunit expression in
      retinospheroids of chick embryo retina cells cultured in vitro and in retina
      cells developing in the embryo (in vivo) were similar, indicating that the
      AMPA/kainate receptor subunits expression in these primary cultures mimics their
      expression in the developing chick retina.

PMID- 12008070
TI  - Sciatic conditioned medium increases survival, proliferation and differentiation
      of retinal cells in culture.
AB  - Many evidences clearly demonstrate that Schwann cells provide trophic support for
      neurons. Different cytokines, including neurotrophins (NTs), are produced and
      released by Schwann cells. These trophic molecules play an important role on
      neuronal survival either during the development or during adult life. Cytokines
      have also a pivotal role on neuronal regeneration after lesions occurring during
      pathological conditions. The aim of this work was to study the effect of sciatic
      conditioned medium (SCM) on rat retinal cells maintained in culture. Our results
      show that treatment with SCM obtained after 14 days in vitro (SCM 14 day) induced
      a three-fold increase in protein content of the culture after 48 h in vitro and
      this value remained equally high up to 72 h. This effect was totally blocked
      either by addition of 30 microM BAPTA-AM, an intracellular calcium chelator, 15
      microM fluorodeoxyuridine, an inhibitor of cell division, or 10 microM genistein
      (geni) plus 1.25 microM chelerythrine chloride (CC), the two last ones inhibitors
      of tyrosine kinases and protein kinase C, respectively. SCM induced an increase
      in [(3)H]-choline uptake and [(3)H]-thymidine incorporation of retinal cells. SCM
      also stimulated an increase in cytoplasmic processes outgrowth of retinal cells
      and survival of retinal ganglion cells. Our results clearly suggest that soluble
      molecules released by sciatic nerve fragments are able to increase the
      proliferation and survival of retinal cells in culture.

PMID- 12008071
TI  - ATP induces proliferation of retinal cells in culture via activation of PKC and
      extracellular signal-regulated kinase cascade.
AB  - Both ATP and acetylcholine can induce the mobilization of intracellular calcium
      in the early developing chick embryo retina, a response that decreases during
      retinal development. In this study, the effects of these transmitters on the
      turnover of phosphoinositides and proliferation of developing retinal cells in
      culture were characterized. While ATP, UTP or carbachol were able to induce a
      >400% accumulation of phosphoinositides in retinal cell cultures, only ATP
      promoted a dose-dependent increase in [(3)H]-thymidine incorporation in cultured
      cells (EC(50)=8.6 microM), a response that was inhibited by the P2 receptor
      antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (0.1 or
      0.25 mM). ADP, but not UTP or adenosine, also stimulated the proliferation of
      retinal cells (EC(50)=5.8 microM), indicating that activation of P2Y1 receptors
      mediates the proliferative response of retinal cells to ATP. The mitogenic effect
      of ATP was completely prevented by the PKC inhibitor chelerythrine chloride (0.5
      microM) and the phospholipase C (PLC) inhibitor U73122 (0.5 microM). PD 98059 (25
      or 50 microM), an inhibitor of the activation of extracellular signal-regulated
      kinases (ERKs) also blocked the increase in [(3)H]-thymidine incorporation
      induced by ATP. Moreover, the effect of ATP was pronounced in cultures obtained
      from retinas at embryonic days 6-8, but not at day 9. Since Muller and bipolar
      cells are the predominant cell types that proliferate at these embryonic stages,
      our data suggest that ATP, through activation of P2Y1 receptors coupled to
      phospholipase C, PKC and MAP kinases, affects DNA synthesis in one or both of
      these cell types in culture.

PMID- 12008072
TI  - Nestin expression persists in astrocytes of organotypic slice cultures from rat
      cortex.
AB  - Nestin is an intermediate filament protein typical for neural precursor cells
      that is down-regulated in the post-natal rodent brain. Re-expression of nestin
      has been observed in reactive astrocytes after injury. In this study, organotypic
      slice cultures from rat cortex were examined for expression of nestin and glial
      fibrillary acidic protein between 2 and 8 weeks in culture. Immunoreactivity for
      nestin and glial fibrillary acidic protein was seen in astrocytes which persisted
      throughout the observation period. Immunofluorescence double labeling showed
      widespread co-localization of nestin and glial fibrillary acidic protein. Image
      analysis revealed that levels of nestin-immunoreactivity plateaued after 5 weeks
      in culture. By comparison nestin immunoreactivity was absent from glial cells of
      the cortex in mature rats. These immunohistochemical findings of a persistent
      expression of nestin in glial cells of organotypic slice culture of the rat
      cortex indicate a different time course of glial maturation in vitro. This
      difference could be related to the altered trophic stimulation in vitro;
      differences in neuronal maturation, activity or survival; slow degeneration of
      the vasculature; or intrinsic properties of astrocytes.

PMID- 12008073
TI  - G(z alpha) deficient mice: enzyme levels in the autonomic nervous system,
      neuronal survival and effect of genetic background.
AB  - Our laboratory has generated a genetically mutant mouse in which the alpha
      subunit of the heterotrimeric GTP binding protein, G(z) has been made
      dysfunctional by homologous recombination to determine its in vivo function.
      These animals show a characteristic failure to thrive phenotype. G(z alpha) is
      expressed in a variety of nervous system tissues as well as in the adrenal
      medulla. We therefore examined the autonomic nervous system of the G(z alpha)
      deficient mouse by measuring the activity of tyrosine hydroxylase and choline
      acetyltransferase in the superior cervical ganglia, submaxillary gland and the
      adrenal medulla. Preliminary results using animals of mixed BALB/c and C57BL/6
      strains gave inconsistent results. Further experiments demonstrated differences
      in the activity of tyrosine hydroxylase and choline acetyltransferase between
      BALB/c and C57BL/6 mouse strains. The analysis of the pure strains showed a
      reduction in the size and enzyme levels of the adrenal gland and submaxillary
      glands of the G(z alpha) deficient mouse suggesting a role for adrenal
      insufficiency and/or nutritional disorders for the failure to thrive phenotype.
      The survival of sympathetic and sensory neurons was also examined in the G(z
      alpha) deficient mouse and in the presence of pertussis toxin, sympathetic but
      not sensory neuronal survival in G(z alpha) deficient mice was significantly
      attenuated. This suggests that in vivo other pertussis toxin sensitive G proteins
      may be recruited to compensate for the loss of G(z alpha).

PMID- 12008074
TI  - Cerebral GABA release and GAD activity in protein- and tryptophan-restricted rats
      during development.
AB  - To evaluate the effects on the GABAergic system, Wistar rats were raised on a
      chronically protein- and tryptophan-restricted diet with 8% protein, based on
      either Purina chow or corn. There was a significant decrease in both body and
      cerebral weight in the restricted animals compared with the control group fed
      with a 23% protein diet. In animals fed mainly corn, glutamic acid decarboxylase
      (GAD) activity increased significantly at the ages studied (14, 30, and 60 days)
      in the cerebral cortex and hippocampus. In the same way, gamma-aminobutyric acid
      (GABA) release decreased significantly in early life in both brain regions, then
      increased in 30-60-day-old animals corn-fed predominantly in the cerebral cortex.
      The reduction in GABA release may be attributable to a decrease in GABAergic cell
      density, which could induce an over-activation of 5-hydroxytryptamine (5-HTergic)
      receptors, leading in turn to the observed enhancement of GAD activity. Taken
      together, these results may represent a plastic response by GABAergic neurons to
      (5-HTergic under-stimulation in mainly corn-fed animals.

PMID- 12008075
TI  - A synaptic potentiation by a protein factor distinct from those induced by
      neurotrophins.
AB  - We report a protein factor(s) contained in the conditioned medium (CM) of the
      Mg(2+)-free treatment induced the synaptic potentiation. This type of
      potentiation shared a different pathway from those induced by neurotrophins.
      Neurotrophins were confirmed to induce a synaptic potentiation in the dissociated
      chick neurons. Furthermore, K252a, an inhibitor of tyrosine kinase, abolished
      this potentiation. Nevertheless, the potentiation induced by the CM was not
      blocked by K252a. In addition, the CM prepared from the chick neurons induced a
      similar potentiation in rat and mouse neurons. These results suggest that the
      protein factor is a novel protein molecule for inducing the potentiation and it
      plays a critical role in the common mechanism for the potentiation between avian
      and mammal.

PMID- 12008076
TI  - Expression and developmental regulation of gap junction connexins cx26, cx32,
      cx43 and cx45 in the rat midbrain-floor.
AB  - Connexins (cx) constitute a family of transmembrane proteins that form gap
      junction channels allowing metabolic and electrical coupling of cellular
      networks. Initial studies on the expression of cx in the developing brain have
      suggested that cx may undergo dynamic changes and may possibly be implicated in
      synchronizing development and differentiation of neural progenitor cells and
      young neurons. We have investigated expression of cx26, cx32, cx43, and cx45 in
      the midbrain floor, where nigrostriatal dopaminergic neurons originate and
      differentiate. This neuron population is of major importance in regulating motor
      functions. Semiquantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) revealed low levels of cx26-mRNA in the midbrain floor at E12, which
      gradually increased during pre- and postnatal development, reaching a maximum in
      the adult. Cx32-mRNA-levels reached a first peak at E16, and showed highest
      levels in adulthood. Cx43 was highly expressed at E12, decreased until E18, and
      subsequently increased again until adulthood. Cx45 mRNA was prominent at all
      developmental ages, but slightly decreased after the first postnatal week. Double
      labeling for the dopaminergic neuronal marker tyrosine hydroxylase (TH), and cx
      immunoreactivities (ir) evaluated by quantitative confocal laser microscopy
      revealed both distinct and similar developmental patterns for the individual cx
      investigated. Cx26 was highest at E14, decreased towards birth, and subsequently
      increased again reaching about 50% of the E14 level in the adult. Cx32-ir peaked
      at E16 and dropped to low levels after birth. Cx43-ir was highest at E12,
      decreased sharply at E14, reached its lowest levels at birth, but modestly
      increased again afterwards. Cx45-ir showed a biphasic pattern, with two prominent
      peaks at E12 and E18, followed by a massive postnatal decrease. Taken together,
      our results reveal that expression and ir of cx in the midbrain floor and
      dopaminergic neurons, respectively, follow cx-type specific patterns that
      temporally coincide with important steps of midbrain morphogenesis, as e.g.
      progenitor cell formation and migration (E12), early differentiation (E14-16),
      target encounter (E16-18) and postnatal functional maturation of the
      nigrostriatal system.

PMID- 12008077
TI  - CD34 and CD117 are overexpressed in AML and may be valuable to detect minimal
      residual disease.
AB  - We estimated by quantitative flow cytometry (FC) the expression of CD13, CD33,
      CD34 and CD117 antigens in cells from 64 patients with acute myeloid leukaemia
      (AML) and 22 normal bone marrows (BMs). The method converts fluorescence
      intensity into number of antigen molecules per cell, measured by antibody binding
      capacity (ABC). The number of molecules per cell in normal BM was 9.5+/-5.7 for
      CD13, 7+/-2.3 for CD33, 6+/-0.7 for CD34, and 6.3+/-1.5x10(3) for CD117. AML
      blasts expressed 11.4+/-12.4 molecules per cell for CD13, 9.5+/-9.7 for CD33,
      74+/-2328.5 for CD34 and 12.5+/-33 x 10(3) for CD117. The number of CD34 and
      CD117 molecules were significantly higher in AML than in normals (P<0.0001 and
      P<0.05, respectively) while only in a few cases, CD13 and CD33 were abnormally
      expressed in myeloblasts. Our results indicate that quantitative analysis of CD34
      and CD117 may be useful to detect minimal residual disease (MRD) and could be
      tested in a future to monitor therapy in AML.

PMID- 12008078
TI  - Potential mechanisms of resistance to cytarabine in AML patients.
AB  - To determine whether the human equilibrative nucleoside transporter 1 (hENT1),
      deoxycytidine kinase (dCK), cytoplasmic 5'-nucleotidase (5NT), cytidine deaminase
      (CDD), topoisomerase I (TOPO I) and topoisomerase II alpha (TOPO II) are involved
      in clinical resistance to cytarabine (ara-C), we analyzed the level of expression
      of these parameters by reverse transcriptase polymerase chain reaction (rt-PCR),
      at diagnosis in the blast cells of 77 acute myeloid leukemia (AML) patients
      treated with ara-C, including 31 for whom samples were collected at first
      relapse. By univariate and/or multivariate analyses, patients with expression of
      5NT or hENT1 deficiency at diagnosis had significantly shorter disease-free
      survival (DFS) and overall survival (OS). These results suggest that expression
      of 5NT and reduced hENT1 in leukemic blasts at diagnosis are correlated with
      clinical outcome and may play a role in resistance mechanisms to ara-C in
      patients with AML.

PMID- 12008079
TI  - Relative levels of alternative transcripts of the ING1 gene and lack of mutations
      of p33/ING1 in haematological malignancies.
AB  - The protein product of the ING1 gene physically interacts with p53 and appears
      necessary for the role of p53 in growth inhibition/apoptosis. Alternative
      splicing of the ING1 gene produces three transcripts: p24/ING1-ALT1, p47/ING1
      ALT2 and p33/ING1. A competitive RT-PCR, which determines the relative levels of
      these transcripts, was employed to study peripheral blood lymphocytes from 49
      patients with haematological malignancies and five normal controls. Both groups
      expressed predominantly the p33/ING1 transcript, with low levels of p24/ING1 and
      p47/ING1. We screened the complete p33/ING1 transcript for sequence variations,
      by non-isotopic RNase cleavage assay (NIRCA); none were found. This study
      suggests that neither perturbation of alternative splicing, nor mutation of
      p33/ING1 plays a significant role in the development of haematological
      malignancies.

PMID- 12008080
TI  - The Brazilian Pediatric Myelodysplastic Cooperative Group strategies: are they
      relevant to improve educational approach and correct diagnosis?
AB  - Brazil is a wide country with huge contrasts. Its peculiarities can highlight
      environmental factors that could influence the frequencies of different cancers.
      The standard treatment and results achieved from several different areas of the
      country may not be found in others. The establishment of a national cooperative
      group has the potential to improve outcomes. The The Brazilian Cooperative Group
      on Pediatric Patients with Myelodysplastic Syndrome (BCG-MDS-PED) was first
      organized in January 1997 as a working group of hematologists, pediatric
      oncologists, pediatric-hematologists, molecular biologists and other
      professionals in order to study pediatric (age <18 years) MDS. Six distinct
      subcommittees constituted with members from several universities: cytology,
      histopathology, clinical, cytogenetics, molecular biology and epidemiology. The
      goals of the BCG-MDS-PED were: (i) to offer support for diagnosis and orientation
      for treatment; (ii) educational support for the colleagues all over the country
      and (iii) research on pathogenesis and new approaches for pediatric MDS patients.
      There are socio-economical differences among the five regions of the country. The
      BCG-MDS-PED believes that it is absolutely necessary to study the clinical,
      cellular, molecular and epidemiological aspects of MDS, taking in account these
      peculiar differences among populations and regions. Since 1997, 114 pediatric
      cases were referred to the BCG-MDS-PED from 21 centres. Seven Brazilian states
      have sent cases to the group, 31 patients were referred from universities, 73
      patients from pediatric oncology units (foundations ) and 10 patients came from
      private clinics. Some of these patients have been followed up and/or treated by
      the physician who referred them to the BCG-MDS-PED for confirmation of the
      initial diagnosis. The majority of these physicians have required orientation on
      diagnostic and treatment issues, as well as to complete cytogenetic and molecular
      studies. From these 114 patients, 64 patients were confirmed as MDS. We believe
      that, the more numerous the MDS-studied cases, the more experienced will be the
      referee group on clinical and laboratory features on childhood MDS in Brazil.

PMID- 12008081
TI  - CD56 expression predicts occurrence of CNS disease in acute lymphoblastic
      leukemia.
AB  - We examined the pre-treatment bone marrow samples from 200 consecutive adult
      patients with acute lymphoblastic leukemia (ALL) treated on various protocols at
      the University of Texas, M.D. Anderson Cancer Center between 1986 and 1998.
      Standard MFC techniques were used to determine CD56 expression on the leukemia
      blasts cells. The expression of CD56 was correlated with clinical characteristics
      at diagnosis, response to therapy, survival and disease-free survival. Blast
      expression of CD56 (> or = 20% of leukemic blasts) was seen in 16 (8%) of
      patients, with a median expression of 67% (range 20-99%). CD56 expression was
      associated with a higher incidence of central nervous system (CNS) disease at
      diagnosis (19% versus 4%; P=0.016). Incidence of CNS disease at any time was
      higher in patients with CD56+ disease (31% versus 14%; P=0.057). Among the 109
      patients uniformly treated with the hyperCVAD regimen, CD56 expression was
      associated with a statistically significant higher incidence of CNS disease (33%
      versus 9%; P=0.026). CD56 expression in ALL is uncommon but may predict a higher
      risk for CNS disease. If these results are confirmed, CD56 expression could be
      used in combination with other high-risk features (e.g. lactate dehydrogenase
      (LDH), S-phase fraction, mature B-cell phenotype) to design a risk-oriented
      approach to CNS prophylaxis.

PMID- 12008082
TI  - A male-specific increase in the HLA-DRB4 (DR53) frequency in high-risk and
      relapsed childhood ALL.
AB  - Previous studies reported significant HLA-DR associations with various leukemias
      one of which is with HLA-DRB4 (DR53) family in male patients with childhood ALL.
      We have HLA-DR-typed 212 high-risk or relapsed patients with childhood (n=114)
      and adult (n=98) ALL and a total of 250 healthy controls (118 children, 132
      adult) by PCR-SSP analysis. The members of the HLA-DRB3 (DR52) family were
      underrepresented in patients most significantly for HLA-DRB1*12 (P=0.0007) and
      HLA-DRB1*13 (P=0.0001). In childhood ALL, the protective effect of DRB3 was
      evident in homozygous form (P=0.001). The DRB4 marker frequency was increased in
      males with childhood ALL (67.4%) compared to age- and sex-matched controls
      (42.1%, P=0.003) and female patients (35.7%, P=0.004). Besides being a general
      marker for increased susceptibility to childhood ALL in males, HLA-DRB4 is over
      represented in high-risk patients. These results further suggest that the HLA
      system is one of the components of genetic susceptibility to leukemia but mainly
      in childhood and in boys only.

PMID- 12008083
TI  - T type 1/type 2 subsets balance in B-cell chronic lymphocytic leukemia--the three
      color flow cytometry analysis.
AB  - The impairments in immune cell functions as well as changes in cytokine network
      are the cause of malignant cell accumulation and secondary immune deficiencies in
      B-cell chronic lymphocytic leukemia (B-CLL). To broaden the knowledge of immune
      system in B-CLL we tried to evaluate the Th1/Th2 and Tc1/Tc2 balance in B-CLL
      patients in comparison with healthy individuals and changes of this pattern
      during disease progression. The three-color flow cytometry technique was used to
      analyze IL-4 and IFNgamma expression in peripheral blood CD3+CD4+ and CD3+CD8+
      cells. The results indicate the dominance of T type 1 cells and T-cell-mediated
      immunity in B-CLL patients that is however shifted towards T type 2 during
      disease progression.

PMID- 12008084
TI  - A metal chelator, diphenylthiocarbazone, induces apoptosis in acute promyelocytic
      leukemia (APL) cells mediated by a caspase-dependent pathway without a modulation
      of retinoic acid signaling pathways.
AB  - A metal chelator, diphenylthiocarbazone (dithizone), has been reported to induce
      differentiation and apoptosis of the human myeloid leukemia cell line HL-60,
      however, very little is known about the mechanism of dithizone-induced apoptosis.
      Here, we report for the first time that dithizone can induce inhibition of
      cellular growth of retinoic acid (RA)-sensitive NB4 and RA-resistant UF-1 APL
      cells via induction of apoptosis but not differentiation. Treatment of NB4 cells
      with dithizone markedly-induced apoptosis, which was associated with the loss of
      mitochondrial transmembrane potentials (Delta Psi(m)) and activation of caspase-3
      and -9. Further investigation of the RA-resistant UF-1 APL cells showed that
      dithizone-induced apoptosis to a lesser extent. However, neither dithizone alone
      nor in combination with all-trans RA induced the expression of myeloid
      differentiation antigen CD11b. Concomitantly, the degradation of PML/RARalpha
      fusion protein was not observed after treatment with dithizone alone, and the
      degradation was not enhanced by the combination of dithizone and all-trans RA. We
      conclude that dithizone, a metal chelator, induced apoptosis without
      differentiation in APL cells in association with Delta Psi(m) collapse and
      caspase-3 and -9 activation.

PMID- 12008085
TI  - Enhanced uptake of antisense oligonucleotides using cationic liposomes and the
      apoptotic effect of idarubicin in K-562 cell line.
AB  - We have evaluated the apoptotic and DNA damaging activity of Idarubicin (IDA) on
      K-562 cells alone and following the uptake of modified antisense
      oligodeoxynucleotides (AS-ODNs) targeting b3a2 mRNA of bcr/abl hybrid gene, after
      treatment with AS-ODNs/DCChol-DOPE (liposomes) complexes. The uptake of FITC
      labeled oligonucleotide-liposomes complexes (FITC-ODNs/DCChol-DOPE) was analyzed
      by flow cytometry and fluorescence microscopy. Both techniques indicated
      cytoplasmic accumulation of labeled liposome complexes following 24h of exposure.
      In absence of liposomes, AS-ODNs uptake was minimal. Pre-treatment of cells with
      AS-ODNs/DCChol-DOPE increased the capability of IDA to induce apoptosis as
      determined by morphology and the comet assay. In contrast, the use of a non-sense
      oligodeoxynucleotide conjugated with liposomes, in the presence of IDA, did not
      increase K-562 cell apoptosis. Nevertheless, DNA damage in IDA treated cells was
      not related to ODNs/liposomes pre-treatment, as determined by the comet assay.
      Our data suggests that DCChol-DOPE increases the uptake of ODNs in K-562 cells,
      and these modified AS-ODNs increase IDA induced apoptosis by decreasing
      p210(bcr/abl) levels in K-562 cells.

PMID- 12008086
TI  - In vitro characterization of hematopoietic microenvironment cells from patients
      with myelodysplastic syndrome.
AB  - In vitro studies on the functional integrity of the hematopoietic
      microenvironment in myelodysplasia have been controversial. Although some of them
      suggest that such a microenvironment is functionally normal, there is increasing
      evidence indicating that there are alterations in the function of
      microenvironment (adherent) cell layers from myelodysplastic syndromes (MDS)
      marrow. Adherent cell layers developed in vitro, however, consist of a mixture of
      different cell types-mostly fibroblasts and macrophages-thus, it is not clear
      which cell type(s) is(are) functionally abnormal in this disorder. In order to
      address this issue, in the present study, we first assessed some functional
      properties of MDS-derived adherent cell layers, as a whole, and then we analyzed
      those same functional properties after separating these cells into two different
      populations: a fibroblast-enriched cell layer and a macrophage-enriched cell
      layer. When whole adherent layers from MDS patients were analyzed, no significant
      differences were observed, as compared to their normal counterparts, in terms of
      morphology and total cell number. A major difference, however, was observed when
      analyzing the production of the cytokines interleukin-6 (IL-6) and tumor necrosis
      factor (TNF-alpha). Indeed, adherent layers from MDS patients produced higher
      levels of these cytokines (2- and 22-fold, respectively), as compared to normal
      layers. When fibroblast- and macrophage-enriched cell layers were analyzed, a
      higher apoptotic index was observed in those derived from MDS marrow (4% of TUNEL
      positive cells in normal fibroblast layers versus 27% in MDS-derived fibroblast
      layers; 7% of TUNEL-positive cells in normal macrophage layers versus 24% in MDS
      macrophage layers). Macrophages from MDS marrow produced significantly higher
      levels of TNF-alpha (nine-fold) than their normal counterparts. MDS-derived
      fibroblasts, on the other hand, produced higher levels of IL-6 (nine-fold), as
      compared to normal fibroblasts. Surprisingly, whereas normal fibroblasts showed a
      discrete production of TNF-alpha, we found a very high production of this
      cytokine in cultures of fibroblasts from MDS patients. In summary, in the present
      study we have demonstrated that, at least in vitro, both fibroblasts and
      macrophages from MDS bone marrow (BM) are functionally abnormal. Such
      abnormalities include an increased apoptotic index, as well as a high production
      of both IL-6 and TNF-alpha.

PMID- 12008087
TI  - Marrow stroma in MDS: culprit or bystander?

PMID- 12008088
TI  - Leptomeningeal relapse of multiple myeloma following allogeneic stem cell
      transplantation.
AB  - Progressive multiple myeloma may manifest features of 'de-differentiation',
      including a plasmablastic appearance, failure to secrete paraprotein,
      extramedullary involvement, and resistance to treatment. A 44-year-old woman with
      kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT).
      Twenty months later she developed paraspinal plasmablastic myeloma in the absence
      of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded
      to chemotherapy. At 30 months she developed myelomatous meningitis, which proved
      resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion
      (DLI). The leptomeningeal disease led to death at 38 months. This is the first
      report of leptomeningeal relapse of myeloma after allografting.

PMID- 12008089
TI  - Cutaneous lymphoblastic lymphoma of putative plasmacytoid dendritic cell
      precursor origin: two cases.
AB  - Although the neoplasm of relatively mature type plasmacytoid dendritic cells
      (pDC) was recently reported, that of pDC-precursor has not yet been defined. We
      experienced two elderly male Japanese patients with reddish skin tumors. The
      histology of the tumors in both patients showed terminal deoxinucleotidyl
      transferase (TdT)-positive lymphoblastic lymphoma (LBL). The pathological cells
      did not express T, B or NK markers, and no rearranged bands were shown for
      immunoglobulin (Ig)-JH, T cell receptor (TCR)-C beta, J gamma, J delta1, and c
      myc. In addition, no Epstein-Barr virus (EBV)-derived DNA was detected in either
      case. The cells were (CD45, CD43, CD74, CD10, and HLA-DR)-positive in both cases,
      and one of the cases showed (CD4, CD36, CD54, CD58 and CD86)-positive
      plasmacytoid lymphoblasts, which appeared to be compatible with intermediate
      cells between human bone marrow lymphoid precursors and mature lymphoid DC. The
      cutaneous LBL in the two cases may, therefore, have been of pDC-precursor origin.

PMID- 12008090
TI  - Unusually prolonged survival of a case of acute megakaryoblastic leukemia
      secondary to long-standing polycythemia vera.

PMID- 12008092
TI  - St. John's wort and depression: efficacy, safety and tolerability-an update.
AB  - St. John's wort (Hypericum perforatum L.) is a medicinal plant traditionally
      used, both externally and internally, in all Europe for many pathologies.
      Paracelsus named it "arnica of the nerves" because of its empirical use in
      nervous diseases. In the last two decades many studies have proved the efficacy
      of some St. John's wort extracts in mild to moderate depression and it has been
      successful as an antidepressant both in Europe and the US. Its high efficacy and
      tolerability is unquestionable and from the clinical studies the activity is
      comparable to other antidepressants while lacking major side effects, making it a
      safe antidepressant.However, recently its potential to induce the metabolism of
      co-administered medications has been reported because it may potentate certain
      enzymes of the cytochrome P450 enzyme system. This resulted in a lowering of
      serum concentration of a number of concomitant drugs, including warfarin,
      digoxin, theophylline, cyclosporin, and indinavir. Many drugs and also several
      common foods and drinks can influence this enzyme system. So, even if its safety
      has been well established, physicians should be aware that St. John's wort
      administration might significantly affect other prescribed medicines.

PMID- 12008091
TI  - Angiogenesis in multiple myeloma.

PMID- 12008093
TI  - Effect of quercitrin on the early stages of hapten induced colonic inflammation
      in the rat.
AB  - Quercitrin is a flavonoid with antiinflammatory activity in experimental colitis,
      associated with an antioxidative action and amelioration of water absorption in
      vivo. However, its mechanism of action is unclear. This study focuses on the
      effect of quercitrin (1 and 5 mg/kg) in the early stages (24 h) of
      trinitrobenzene sulfonic acid colitis. Treatment with the flavonoid prevented the
      increase in colonic malondialdehyde and inhibited nitric oxide synthase and
      alkaline phosphatase activity but had no significant effects on observable
      damage. No effect on neutrophil infiltration (myeloperoxidase) was observed. On
      the other hand, quercitrin exerted complex effects on colonic hydroelectrolytic
      transport, showing a slight potentiation of water absorption in vivo (5 mg/kg) as
      well as a normalization of carbachol stimulated electrogenic ionic transport in
      the proximal colon in vitro (5 mg/kg). It is concluded that the beneficial
      effects of quercitrin on trinitrobenzene sulfonic acid chronic colitis arise from
      an early downregulation of the inflammatory cascade that is associated with
      amelioration of the disturbances in hydroelectrolytic transport.

PMID- 12008094
TI  - Effect of lignans isolated from Hernandia nymphaeifolia on estrogenic compounds
      induced calcium mobilization in human neutrophils.
AB  - The effect of five lignans isolated from Hernandia nymphaeifolia on estrogenic
      compounds (17beta-estradiol, tamoxifen and clomiphene)-induced Ca(2+)
      mobilization in human neutrophils was investigated. The five lignans were epi
      yangambin, epi-magnolin, epi-aschantin, deoxypodophyllotoxin and yatein. In
      Ca(2+)-containing medium, the lignans (50-100 microM) inhibited 10 microM 17beta
      estradiol- and 5 microM tamoxifen-induced increases in intracellular free Ca(2+)
      levels ([Ca(2+)](i)) without changing 25 microM clomiphene-induced [Ca(2+)](i)
      increase. 17beta-estradiol and tamoxifen increased [Ca(2+)](i) by causing Ca(2+)
      influx and Ca(2+) release because their responses were partly reduced by removing
      extracellular Ca(2+). In contrast, clomiphene solely induced Ca(2+) release. The
      effect of the lignans on these two Ca(2+) movement pathways underlying 17beta
      estradiol- and tamoxifen-induced [Ca(2+)](i) increases was explored. All the
      lignans (50-100 microM) inhibited 10 microM 17beta-estradiol-and 5 microM
      tamoxifen-induced Ca(2+) release, and 17beta-estradiol-induced Ca(2+) influx.
      However, only 100 microM epi-aschantin was able to reduce tamoxifen-induced
      Ca(2+) influx while the other lignans had no effect. Collectively, this study
      shows that the lignans altered estrogenic compounds-induced Ca(2+) signaling in
      human neutrophils in a multiple manner.

PMID- 12008095
TI  - Dietary iron-deficiency up-regulates hephaestin mRNA level in small intestine of
      rats.
AB  - Hephaestin is a protein, recently found from the study of sla (sex-linked anemia)
      mouse. Hephaestin is suggested to transport iron from intestinal enterocytes into
      the circulation. Iron is essential for living and for humans to maintain a
      constant total iron concentration in whole body. In this study, it was found that
      dietary iron-deficiency up-regulated hephaestin mRNA level in the proximal small
      intestine of rats. Therefore, it is suggested that in dietary iron-deficiency,
      hephaestin gene expression in proximal small intestine is up-regulated to absorb
      more iron from diet.

PMID- 12008096
TI  - Pregnancy-associated increase in rat systemic arteries endothelial nitric oxide
      production diminishes vasoconstrictor but does not enhance vasodilator responses.
AB  - Late pregnancy in rats is characterized by a decrease in arterial pressure and in
      isolated arterial vessels response to vasoconstrictors. In uterine arteries the
      pregnancy-associated attenuation of the response to vasoconstrictors has been
      attributed to an increase in basal and agonist-induced endothelial NO production.
      However, the role of NO in pregnancy-associated changes of systemic arteries
      reactivity to vasoactive agents remains to be fully elucidated. We examined
      whether pregnancy influences the reactivity of systemic arteries to vasodilator
      or vasoconstrictor agents through NO-dependent mechanisms. Thoracic aortic rings
      and mesenteric arterial bed of late pregnant rats showed refractoriness to
      phenylephrine-induced vasoconstriction that was abolished by NO synthase
      inhibition. The potency of L-NNA to enhance tension of aortic rings
      preconstricted with phenylephrine (10-20% of their maximal response) was
      significantly lower in preparations from pregnant animals. In phenylephrine
      contracted aortas and mesenteric bed, the effects of the endothelium-dependent
      vasodilators acetylcholine, A23187 and bradykinin, were not influenced by
      pregnancy. Similarly, pregnancy did not affect the vasodilator responses of
      adenosine, isoproterenol, capsaicin, nitroprusside, forskolin, and Hoe234 in the
      mesenteric bed. NO synthase activity measured by determining the conversion of L
      [(3)H]-arginine to L-[(3)H]-citrulline in aorta and mesenteric arteries
      homogenates was not altered by pregnancy. These findings show that endothelial
      dependent and -independent vasodilators action as well as NO synthase activity in
      systemic arteries is uninfluenced by pregnancy, whereas pregnancy-associated
      hyporeactivity of systemic arteries to vasoconstrictors is related to an enhanced
      endothelial NO production either spontaneous or elicited directly or indirectly
      by vasoconstrictor agents. This interpretation implies that the enhanced NO
      production observed in systemic arteries during late pregnancy involves cellular
      pathways other than the ones involved in the response to endothelium-dependent
      vasodilators such as acetylcholine.

PMID- 12008097
TI  - Low dose ethanol potentiates indomethacin induced inhibition of wound re
      epithelialization in duodenal monolayers.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastroduodenal mucosal
      injury and ulceration, and delay ulcer healing. In contrast, the effects of low
      dose ethanol in induction of gastroduodenal mucosal injury, and the subsequent
      wound repair remains unclear. The aim of this study was to determine, using an in
      vitro duodenal epithelial wound model, whether low clinically relevant doses of
      ethanol or indomethacin interfere with the wound re-epithelialization of duodenal
      epithelial monolayers. The possible potentiating effect of ethanol on
      indomethacin modulation of duodenal re-epithelialization was also examined. In
      vitro epithelial wounds were created in confluent IEC-6 duodenal epithelial
      monolayers by a razor blade scrape. Ethanol at low concentrations (0.25, 0.5,
      0.75%) did not have significant effect on duodenal wound re-epithelialization.
      Similarly, low doses of indomethacin (.01,.05, 0.1 mM) also did not have a
      significant effect on wound re-epithelialization. However, the combination of
      ethanol (0.5 or 0.75%) and indomethacin (0.1mM) produced a marked inhibition of
      IEC-6 re-epithelialization. At the low doses used, ethanol and indomethacin
      (individually or in combination) did not have direct cytotoxic effect on IEC-6
      cells. Ethanol or indomethacin (at the studied concentrations) had only minimal
      effect on the actin stress fibers in the cells at the migration front. However,
      in combination, they almost completely abolished the actin stress fibers at the
      migration front. These findings demonstrate that while low clinically relevant
      doses of ethanol and indomethacin individually do not affect re-epithelialization
      of wounded duodenal epithelial monolayers, in combination they produce a
      significant inhibition.

PMID- 12008098
TI  - Depression is associated with an increase in the expression of the platelet
      adhesion receptor glycoprotein Ib.
AB  - There is a significant association between cardiovascular disease and depression.
      Previous studies have documented changes in platelets in depression. It is
      unknown if depression causes functional changes in platelet surface receptors.
      Therefore, we analyzed (1) the surface expression of glycoprotein (GP)Ib and the
      integrin receptor alpha(IIb)beta(IIIa), receptors involved in platelet adhesion
      and aggregation, (2) CD62 (P-selectin) and CD63, integral granule proteins
      translocated during platelet activation, (3) platelet aggregation in response to
      ADP and (4) plasma levels of glycocalicin and von Willebrand factor (vWF), in
      depressed patients compared to healthy volunteers. Fifteen depressed patients
      with a Hamilton depression score of at least 22 and fifteen control subjects were
      studied. Platelets were assessed for surface expression levels of GPIb,
      alpha(IIb)beta(IIIa), CD62 and CD63 by flow cytometry. Genomic DNA was isolated
      to investigate a recently described polymorphism in the 5' untranslated region of
      the GPIbalpha gene. The number of GPIb receptors was significantly increased on
      the surface of platelets from patients with depression compared to control
      subjects. Surface expression of CD62 was also significantly increased in the
      depressed patients versus control subjects. There was no significant difference
      between depressed patients and healthy volunteers in the surface expression of
      alpha(IIb)beta(IIIa) or CD63, or in glycocalicin or vWF plasma concentration, or
      ADP-induced aggregation. There was no difference in allele frequency of the Kozak
      region polymorphism of the GPIbalpha gene, which can affect GPIb expression. The
      results of this study demonstrate that the number of GPIb receptors on platelets
      are increased in depression and suggest a novel risk factor for thrombosis in
      patients with depression.

PMID- 12008099
TI  - Effect of clomiphene on Ca(2+) movement in human prostate cancer cells.
AB  - The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca(2+)
      levels ([Ca(2+)](i)) in populations of PC3 human prostate cancer cells was
      explored by using fura-2 as a Ca(2+) indicator. Clomiphene at concentrations
      between 10-50 microM increased [Ca(2+)](i) in a concentration-dependent manner.
      The [Ca(2+)](i) signal was biphasic with an initial rise and a slow decay. Ca(2+)
      removal inhibited the Ca(2+) signal by 41%. Adding 3 mM Ca(2+) increased
      [Ca(2+)](i) in cells pretreated with clomiphene in Ca(2+)-free medium, confirming
      that clomiphene induced Ca(2+) entry. In Ca(2+)-free medium, pretreatment with 50
      microM brefeldin A (to permeabilize the Golgi complex), 1 microM thapsigargin (to
      inhibit the endoplasmic reticulum Ca(2+) pump), and 2 microM carbonylcyanide m
      chlorophenylhydrazone (to uncouple mitochondria) inhibited 25% of 50 microM
      clomiphene-induced store Ca(2+) release. Conversely, pretreatment with 50 microM
      clomiphene in Ca(2+)-free medium abolished the [Ca(2+)](i) increase induced by
      brefeldin A, thapsigargin or carbonylcyanide m-chlorophenylhydrazone. The 50
      microM clomiphene-induced Ca(2+)release was unaltered by inhibiting phospholipase
      C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)
      1H-pyrrole-2,5-dione (U73122). Trypan blue exclusion assay suggested that
      incubation with clomiphene (50 microM) for 2-15 min induced time-dependent
      decrease in cell viability by 10-50%. Collectively, the results suggest that
      clomiphene induced [Ca(2+)](i) increases in PC3 cells by releasing store Ca(2+)
      from multiple stores in an phospholipase C-independent manner, and by activating
      Ca(2+) influx; and clomiphene was of mild cytotoxicity.

PMID- 12008110
TI  - Spin trapping evidence for alcohol-associated oxidative stress.
AB  - The spin trapping method combined with EPR spectroscopy has been employed by a
      number of laboratories to study alcohol-induced oxidative stress. Ethanol is
      converted to a free radical metabolite, the 1-hydroxyethyl radical in chemical
      reactions that generate hydroxyl radicals, in incubations of rat liver microsomes
      and in vivo. Furthermore, both acute and chronic ethanol administration leads to
      formation of radicals in the liver that are presumed to be products of lipid
      peroxidation. In general, overall radical production is enhanced by treatments
      known to be involved in alcoholic liver injury, such as chronic alcohol
      administration along with high levels of dietary fat.

PMID- 12008100
TI  - Production of growth related oncogene protein-alpha in human umbilical vein
      endothelial cells stimulated with soluble interleukin-6 receptor-alpha: role of
      signal transducers, janus kinase 2 and mitogen-activated kinase kinase.
AB  - Growth-related oncogene protein-alpha (GRO-alpha) is a member of the C-X-C
      chemokine family with a wide variety of biological activities. We studied the
      production of GRO-alpha by human umbilical vein endothelial cells (HUVEC) in
      response to the stimulation with soluble form of interleukin-6 receptor alpha
      (sIL-6R). sIL-6R stimulated HUVEC to express GRO-alpha mRNA and secrete GRO-alpha
      protein in concentration-and time-dependent manners. The sIL-6R-induced GRO-alpha
      expression was inhibited by the pretreatment of the cells with AG490, a janus
      kinase 2 (JAK2) inhibitor, or with U0126, a MAP kinase-ERK kinase (MEK)
      inhibitor. sIL-6R also induced the phosphorylation of both Src homology 2-protein
      tyrosine phosphatase-2 (SHP-2), signal transducer and activator of transcription
      3 (STAT3) and MEK. AG490 pretreatment inhibited the MEK phosphorylation but did
      not affect the STAT3 phosphorylation. We conclude that sIL-6R induces GRO-alpha
      expression in HUVEC through the activation of JAK2 and MEK.

PMID- 12008111
TI  - Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis.
AB  - This review discusses the relevance of oxidative damage to metal-induced toxicity
      and carcinogenesis. Presented are important facts and mechanistic concepts on the
      capacity of selected transition metals, mainly Ni, but also Cu, Co, Cr, and
      briefly several others, to generate active oxygen species and other reactive
      intermediates under physiological conditions. These metals are known to be toxic
      and/or carcinogenic contaminants of the occupational and general environments.
      Their redox activity may underlay the mechanism of mediation of oxidative damage
      to cell constituents. The presentation is focused on selected issues relative to
      genetic and epigenetic toxicity and illustrated with examples of metal-mediated
      oxidative damage to the principal components of chromatin, i.e., DNA, histones,
      and protamines.

PMID- 12008112
TI  - Effect of diet on cancer development: is oxidative DNA damage a biomarker?
AB  - Free radicals and other reactive species are generated in vivo and many of them
      can cause oxidative damage to DNA. Although there are methodological
      uncertainties about accurate quantitation of oxidative DNA damage, the levels of
      such damage that escape immediate repair and persist in DNA appear to be in the
      range that could contribute significantly to mutation rates in vivo. The
      observation that diets rich in fruits and vegetables can decrease both oxidative
      DNA damage and cancer incidence is consistent with this. By contrast, agents
      increasing oxidative DNA damage usually increase risk of cancer development. Such
      agents include cigarette smoke, several other carcinogens, and chronic
      inflammation. Rheumatoid arthritis and diabetes are accompanied by increased
      oxidative DNA damage but the pattern of increased cancer risk seems unusual.
      Other uncertainties are the location of oxidative DNA damage within the genome
      and the variation in rate and level of oxidative damage between different body
      tissues. In well-nourished human volunteers, fruits and vegetables have been
      shown to decrease oxidative DNA damage in several studies, but data from short
      term human intervention studies suggest that the protective agents are not
      vitamin C, vitamin E, beta-carotene, or flavonoids.

PMID- 12008113
TI  - EC-SOD and the response to inflammatory reactions and aging in mouse lung.
AB  - The lung is exposed to high oxygen tension and oxygen free radicals have been
      implicated in many pathologies of the organ. Extracellular superoxide dismutase
      occurs in high concentration in the lung and protects against hyperoxia-induced
      inflammation. We hypothesized that the enzyme might ameliorate other types of
      inflammation as well as aging-related changes of the organ. Tracheal instillation
      of endotoxin plus zymosan into extracellular superoxide dismutase knockout and
      wild-type mice resulted in a marked neutrophilic inflammation and increases in
      inflammatory cytokines, protein, and lactate dehydrogenase activity in the
      bronchoalveolar lavage fluid. There were no significant differences between the
      genotypes. Repeated challenges with ovalbumin caused an allergic inflammation
      with increases in eosinophils, interleukin-5, protein, and lactate dehydrogenase
      activity in the bronchoalveolar lavage fluid. Only minimal differences between
      the genotypes were found. In lungs from 2-year-old mice, marginal increases in
      inflammatory variables and fibrosis were found in the knockout mice. In
      conclusion, extracellular superoxide dismutase had a negligible role in the
      present inflammation and allergy models and for the long-term integrity of the
      organ.

PMID- 12008114
TI  - Electron paramagnetic resonance spin trapping investigation into the kinetics of
      glutathione oxidation by the superoxide radical: re-evaluation of the rate
      constant.
AB  - The ability of glutathione to scavenge the superoxide radical is a matter of
      serious contention in the literature: reported values for the second-order rate
      constant range from 10(2) to greater than 10(5) M(-1) s(-1). The physiological
      implications of this discrepancy will determine, for example, whether or not
      glutathione can compete with Mn-superoxide dismutase for reaction with the
      radical in the mitochondrial matrix, leading to formation of the potentially
      harmful glutathionyl radical. Several authors have investigated the kinetics of
      glutathione oxidation by superoxide using spectrophotometric assays, based on
      competition between either ferricytochrome c or epinephrine for reaction with the
      radical. However, these approaches have received criticism because the
      contributions of various secondary reactions to the overall kinetics have been
      largely overlooked (e.g., the reduction of ferricytochrome c by glutathione). In
      the present investigation, we have used electron paramagnetic resonance
      spectroscopy to monitor competition between GSH and the spin trap 5,5-dimethyl-1
      pyrroline N-oxide for reaction with superoxide. This method has been used
      previously and a rate constant of 1.8 x 10(5) M(-1) s(-1) obtained (Dikalov, S.;
      Khramtsov, V.; Zimmer, G. Arch. Biochem. Biophys. 326:207-218; 1996). However, we
      demonstrate that this value is a gross overestimation because the spectrum of the
      hydroxyl radical adduct of the spin trap was incorrectly assigned to the
      glutathionyl radical adduct. The relatively high yield of the DMPO hydroxyl
      radical adduct is shown to be due to the two-electron reduction of the
      corresponding superoxide radical adduct by glutathione. Taking these factors into
      consideration, we estimate the second order rate constant for the oxidation of
      glutathione by superoxide to be approximately 200 M(-1) s(-1).

PMID- 12008115
TI  - Molecular exploration of age-related NF-kappaB/IKK downregulation by calorie
      restriction in rat kidney.
AB  - Accumulating evidence strongly suggests that oxidative stress underlies aging
      processes, and that in a variety of organisms, calorie restriction (CR) retards
      these processes, thereby extending their lifespan. Recent studies revealed that
      the anti-aging action of CR depends on its anti-oxidative mechanism. In previous
      papers, we reported that aging activates the redox-sensitive transcription
      factor, NF-kappaB, and further reported that age-related NF-kappaB activation
      correlates with age-related oxidative stress. In the present paper, we present
      evidence that increased NF-kappaB binding activity during aging is elicited
      through the phosphorylation of IkappaB kinase (IKK), causing a degradation of
      IkappaBalpha and IkappaBbeta. We further show that CR inhibits IKK activation,
      down-regulating NF-kappaB activation as evidenced by increased bound IkappaBalpha
      and IkappaBbeta proteins in cytoplasm. These findings led to the conclusions that
      age-related oxidative stress may be a primary cause of up-regulated and altered
      NF-kappaB activity in aged kidney, and that the anti-oxidative action of CR is a
      major force responsible for the maintenance of a properly functioning NF
      kappaB/IkappaB-IKK signaling pathway, which might be involved in CR's life
      prolonging action.

PMID- 12008116
TI  - Oxidative stress mediates cell surface expression of SS-A/Ro antigen on
      keratinocytes.
AB  - Exposure to ultraviolet radiation exacerbates the skin lesions of autoimmune
      diseases, and is known to induce cell surface expression of SS-A/Ro antigen on
      keratinocytes in vitro. Following up on recent reports on ultraviolet-B (UVB)
      induced oxidative stress, we examined the role of oxidative stress in the surface
      expression of SS-A/Ro antigen on human keratinocytes. First, the exclusive
      induction by UVB irradiation of the 52-kDa protein (Ro52) but not of the 60-kDa
      protein (Ro60) of SS-A/Ro antigen was demonstrated by means of indirect
      immunofluorescence. The surface expression of Ro52 induced by UVB irradiation was
      concentration-dependently inhibited by N-acetyl-L-cysteine, an antioxidant.
      Furthermore, surface expression of Ro52 was similarly induced by diamide, a
      chemical oxidant. We next used Hoechst 33342 staining and the TUNEL assay to
      demonstrate that a low dose (20 mJ/cm(2)) of UVB did not induce apoptosis but
      induced the surface expression of Ro52. Moreover, zVAD-fmk, a pan-caspase
      inhibitor, did not inhibit UVB-induced surface expression of Ro52 even at a high
      dose (200 mJ/cm(2)) of UVB, which was sufficient to induce apoptosis in
      keratinocytes in the absence of zVAD-fmk. Taken together, we concluded that UVB
      induced surface expression of Ro52 on keratinocytes is mediated by oxidative
      stress through a pathway other than apoptosis.

PMID- 12008117
TI  - Induction of microsomal epoxide hydrolase by sulfur amino acid deprivation via
      the pathway of C-Jun N-terminal kinase and its extracellular exposure during cell
      death.
AB  - Microsomal epoxide hydrolase (mEH), an epoxide detoxifying enzyme and putative
      cell surface autoantigen, is inducible by xenobiotics and by certain
      pathophysiological conditions (e.g., tumorigenesis and protein-calorie
      malnutrition). The present study was designed to determine mEH expression in
      H4IIE cells during cell death initiated by sulfur amino acid deprivation (SAAD)
      and to identify the signaling pathway for the enzyme induction. SAAD induced cell
      death at 48-72 h with translocation of Bax to mitochondria and increased
      mitochondrial permeability with cytochrome c release, both of which were
      prevented by SB203580 or by dominant-negative JNK1 [JNK1(-)] stable transfection.
      Caspase-3 activity was only marginally increased by SAAD. Neither genomic DNA
      fragmentation nor poly(ADP-ribose) polymerase cleavage was observed during SAAD
      induced cell death. Thus, SAAD induced cell death independent of caspase
      activation. This was supported by the observation that benzyloxycarbonyl-Val-Ala
      Asp-fluoromethyl ketone, a general caspase inhibitor, did not prevent cell death.
      The levels of mEH mRNA and protein were notably increased in cells under SAAD for
      48-72 h. The induction of mEH occurred in parallel with cell death. Whereas SAAD
      induced cell death resulted from both JNK1 and p38 kinase activation, mEH
      induction was decreased only by JNK1(-) transfection. Immunocytochemistry
      revealed that mEH protein was intensely stained in dying cells, cellular
      fragments and cell debris. Furthermore, the number of cells positive for surface
      mEH substantially increased by SAAD, as evidenced by flow cytometry analysis.
      These results demonstrated that SAAD induced nonapoptotic cell death with Bax
      translocation to mitochondria and mitochondrial cytochrome c release, but not
      through caspase-3 activation, and that mEH was induced by SAAD via the pathway of
      JNK1, but not ERK1/2 or p38 kinase, in parallel with cell death.

PMID- 12008118
TI  - Reoxygenating microvascular endothelium exhibits temporal dissociation of NF
      kappaB and AP-1 activation.
AB  - Alterations of cellular redox balance in microvascular endothelium results in
      changes of essential cell functions. These alterations may arise, in part, due to
      modifications in the pattern of gene expression produced by transcription factor
      activation. Endothelium subjected to hypoxia/reoxygenation becomes redox
      imbalanced, thereby leading to activation and perhaps production of a
      proinflammatory state. A human dermal microvascular endothelial cell line (HMEC
      1) was exposed to 6 h of hypoxia (3% O(2)) followed by return to normoxia
      atmospheric conditions. Reactive oxygen species (ROS) generation
      (dichlorofluoroscein epifluorescence) was immediate and significant following
      reoxygenation. Electrophoretic mobility shift assays revealed activation of the
      oxidant sensitive transcription factors NFkappaB and AP-1, though importantly,
      peak activation of each factor was separated temporally by greater than 60 min.
      NFkappaB activation occurred without degradation of the inhibitory protein
      IkappaBalpha. Reoxygenating HMEC-1 exhibited a greater than 500-fold increase in
      polymorphonuclear neutrophil (PMN) adhesion when compared to normoxic controls.
      Exposure of reoxygenating HMEC-1 to the antioxidant pyrrolidine dithiocarbamate
      produced complete abrogation of NFkappaB activation and the intensive PMN
      adhesion observed in untreated, posthypoxic HMEC-1. Though rexoygenation stress
      induced significant upregulation of PMN adhesion, no upregulation of interleukin
      8 production was observed. Our results suggest that ROS generation occurring in
      endothelium following onset of reoxygenation stress signals activation of key
      transcription factors and that their activation takes place in a temporal
      fashion. The temporal feature of transcription factor activation may be key to
      production of a postischemic proinflammatory state.

PMID- 12008119
TI  - The potential of flow-through optosensors in pharmaceutical analysis.
AB  - The fundamental principles of flow-through optosensors, together with the most
      significant procedures and alternatives developed in the applications of flow
      through optosensors to pharmaceutical analysis are reviewed. The most frequently
      used solid sensing zones, flow-through cells, manifolds, regeneration step and
      types of detection are considered. Single parameter, biparameter, and
      multiparameter sensors developed are reviewed and their most relevant features
      presented. Finally, a critical comparison with other analytical
      methodologies/techniques is performed and the potential of flow-through
      optosensors in pharmaceutical analysis and their future trends discussed.

PMID- 12008120
TI  - Validation of HPLC and GC-MS systems for bisphenol-A leached from hemodialyzers
      on the basis of FUMI theory.
AB  - This paper proposes a method for the validation of chromatography systems in
      which many experiments to estimate SD or RSD are difficult or impossible to carry
      out because of time, cost, etc. HPLC systems with UV-Vis and fluorescence
      detectors and GC-MS system for bisphenol-A leached from hemodialyzers are taken
      as an example. Examined as validation characteristics are not only the ordinary
      quantities (precision, accuracy, range, limit of detection (LOD), limit of
      quantitation (LOQ), specificity and linearity) but also precision plots
      (measurement RSD vs. concentration), 95% confidence intervals of calibration
      lines and LOD signals over baselines. The precision plots, calibration confidence
      intervals and LOD signals are shown to be advantageous to validate and compare
      the analytical performance of the systems. The LOD, LOQ, precision plots and 95%
      confidence intervals of calibration lines are all derived from the SD of
      measurements and the reliability of these quantities and plots depends totally on
      the reliability of the SD estimates. This paper uses a probability theory, called
      the FUMI theory, to estimate as exact a measurement SD as possible without the
      replication. The precision of the HPLC and GC-MS systems is shown to coincide
      with the repeatability obtained by the repetition of measurements.

PMID- 12008121
TI  - A validated LC method for the determination of clopidogrel in pharmaceutical
      preparations.
AB  - A stability indicating, reversed-phase high-performance liquid chromatographic
      method was developed and validated for the determination of clopidogrel in
      pharmaceutical dosage forms. The determination was performed on a semi-micro
      column, BDS C8 (250 x 2.1 mm i.d., 5 microm particle size); the mobile phase
      consisted of a mixture of 0.010 M sodium dihydrogen phosphate (pH 3.0) and
      acetonitrile (35:65, v/v), pumped at a flow rate 0.30 ml min(-1). The UV detector
      was operated at 235 nm. The retention times for clopidogrel and naproxen, which
      was used as internal standard, were 3.08 and 6.28 min, respectively. Calibration
      graphs are linear (r better than 0.9991, n=6), in concentration range 1.00-3.00
      microg ml(-1) for clopidogrel. The intra- and inter-day RSD values were less than
      1.96%, while the relative percentage error E(r) was less than 2.0% (n=5).
      Detection and quantitation limits were 0.12 and 0.39 micro ml(-1), respectively.
      The method was applied in the quality control of commercial tablets and content
      uniformity test and proved to be suitable for rapid and reliable quality control.

PMID- 12008122
TI  - Rapid quantification of constituents in St. John's wort extracts by NIR
      spectroscopy.
AB  - A quantitative near-infrared reflectance spectroscopy (NIRS) method was
      established for the determination of two major constituents (hyperforin and
      I3,II8-biapigenin) in St. John's wort extracts. Hyperforin was chosen due to the
      fact that it is found in a concentration range from 1 to 5%, a common one for
      NIRS determinations. I3,II8-Biapigenin on the other hand was selected as a
      constituent with very low concentrations (0.1-0.7%) but an extensive chromophore
      that allows very precise measurements in the ultraviolet (UV) and thus exact
      reference values that are vital for proper NIRS calibrations. Reference
      measurements were performed by reversed-phase high performance liquid
      chromatography (HPLC), determining the constituents' content in 35 pharmaceutical
      dry extracts of different origins. The reference method was validated according
      to the ICH guideline Q2B. Using partial-least squares (PLS) regression a
      multivariate calibration was done for the two ingredients each (PLS1).
      Satisfactory calibration statistics were obtained for hyperforin with a root mean
      square error of calibration (RMSEC) of 0.17 and a root mean square error of
      prediction (RMSEP) of 0.22 at a concentration range from 1 to 6% in the dry
      extracts. Due to the very low concentrations of I3,II8-biapigenin the accuracy of
      prediction is somewhat lower. However, it is possible to obtain very good results
      and reliable prediction by dividing the concentration range at 0.35%. The study
      emphasizes the potential of NIRS as a rapid and highly effective alternative
      method to conventional quantitative analysis of plant extracts.

PMID- 12008123
TI  - RP-LC determination of oleane derivatives in Terminalia arjuna.
AB  - A rapid sensitive and reproductive reversed phase high performance liquid
      chromatographic method with photo diode arrray detection is described for the
      simultaneous quantification of major oleane derivatives: arjunic acid (4),
      arjunolic acid (3), arjungenin (2) and arjunetin (1) in Terminalia arjuna
      extract. The method involves the use of a Waters Spherisorb S10 ODS2 column (250
      x 4.6 mm, I.D., 10 microm) and binary gradient mobile phase profile. The various
      other aspects of analysis viz. Extraction efficiency, peak purity and similarity
      were validated using a photo diode array detector.

PMID- 12008124
TI  - LC determination and degradation study of droperidol.
AB  - A specific, high performance liquid chromatographic method for the determination
      of droperidol in the presence of its degradation products is described. The
      method is based on the use of an amide functionalized bonded phase column (LC
      ABZ(+) Plus) and a simple mobile phase of methanol-sodium phosphate monobasic
      (0.05 M, pH 4.5) (40:60, v/v). It enables the resolution of eight compounds from
      the parent drug and from each other. The degradation was carried out in
      hydrochloric acid, sodium hydroxide and hydrogen peroxide. The main degradation
      products were identified. Application of the assay for a commercial preparation
      of droperidol for injection is presented.

PMID- 12008125
TI  - Determination of mineral content of active dry yeast used in pharmaceutical
      formulations.
AB  - The efficiency of seven common methods of digestion of active dry yeast (ADY),
      which is used in anticariogenic dental formulations, was evaluated for the
      analytical determination of Fe, Zn, Ca, Mg, Na and K. Four wet-acid digestion and
      three dry ashing methods are compared in consideration of their estimated
      reproducibility and metal concentrations obtained. HNO(3), HNO(3)+HCl,
      HNO(3)+H(2)SO(4) and HNO(3)+HClO(4) were applied for wet digestion of the samples
      in medium temperatures, while dry ashing at higher temperature with Mg(NO(3))(2)
      or SrCl(2) as ashing aid agents, were the alternative methods. The final
      solutions were subsequently analyzed for Fe, Zn, Ca and Mg by flame atomic
      absorption spectroscopy (FAAS) and for Na and K by atomic emission spectroscopy
      (AES). Two multivariate statistical methodologies, Analysis of variance (ANOVA)
      and the Kruskal-Wallis test were applied for the interpretation of the results.
      Seven additional statistical tests (least-significant difference, Bonferoni,
      Duncan multiple range, Student-Newman-Keuls, Tuckey significant difference,
      Tuckey b and Scheffe) were used and proved useful to estimate which of the
      decomposition methods are outliers. The ideographic approach enabled the
      comparison of the methods in terms of complexity and difficulty of their steps.
      Zn and Mg could be reliably determined by any one of the tested methods, while
      for the other elements, the most powerful method was found and the obtained
      recoveries were found (>95%).

PMID- 12008126
TI  - Evaluation of amino sugar, low molecular peptide and amino acid impurities of
      biotechnologically produced amino acids by means of CE.
AB  - As the second part of our studies on the impurity profiles of amino acids
      produced by biotechnological processes, a micellar electrokinetic chromatography
      (MEKC) was applied to determine amino sugars, low molecular peptides and amino
      acids as potential expected impurities at a level 0.1% w/w. 3-(4
      Carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) was found to be suitable as a
      labeling reagent for laser induced fluorescence (LIF) detection. The labeling
      reaction was optimized to achieve maximum reaction yields and reproducibility for
      all groups of substances. The 'level 0.1%' was chosen as
      quantities/concentrations in such a way that the major reagent peak becomes
      comparable with the impurities at this level, and the minor reagent peaks
      (<0.01%) are not able to cover other peaks at the level of interest. The reaction
      optimization and the validation studies were performed with model mixtures of
      representative amino sugars, low molecular peptides and amino acids. A linearity
      range of labeling of three orders of magnitude was achieved. The total precision
      of the method, including the labeling reproducibility was studied and for all
      test substances relative standard deviation less than 5% were obtained. The
      accuracy was evaluated by performing recovery experiments at three concentrations
      covered a 50-200% interval of the level 0.1%. Confidence intervals below +/-2.5%
      (lambda=0.05, n=9) of the target were found sufficient for purity tests.

PMID- 12008127
TI  - LC determination of aminoglutethimide enantiomers as dansyl and fluorescamine
      derivatives in tablet formulations.
AB  - Determination of dansyl (AG-DNS) and fluorescamine (AG-F) derivatives of rac
      aminoglutethimide in tablet formulation by HPLC has been achieved on a cellulose
      tris-(3,5-dimethylphenyl carbamate), known as Chiralcel OD and OD-R under normal
      and reversed phase columns, respectively, using a fluorescence detector
      (lambda(ex), 360 nm; lambda(em), 530 nm for AG-DNS derivatives; lambda(ex), 395
      nm, lambda(em), 495 nm for fluorescamine derivatives (AG-F)). The best results
      were obtained with mobile phase ethanol:cyclohexane:methanol (95:5:2 v/v/v) for
      AG-DNS derivatives and acetonitrile:0.5% ortho-phosphoric acid (85:15 v/v)
      containing 0.26 mM 1-hexanesulfonic acid sodium salt (HSA) for AG-F,
      respectively. The lower limit of detection (signal to noise ratio of 3:1) were
      found to be 20 ng ml(-1) for each enantiomer for AG-DNS and 20.5 ng ml(-1) for
      each diastreoisomer for AG-F.

PMID- 12008128
TI  - Determination of celecoxib, a COX-2 inhibitor, in pharmaceutical dosage forms by
      MEKC.
AB  - A micellar electrokinetic chromatographic (MEKC) method was developed for the
      quantification of celecoxib, a COX-2 inhibitor in pharmaceutical dosage forms
      within the total analysis time of 7 min. The method has been validated and proven
      to be rugged. The quantification was carried out at 35 degrees C and 25 kV, using
      a 25 mM borate buffer (pH 9.3), 25 mM sodium dodecyl sulphate with an extended
      light path capillary (48.5 cm x 50 micro I.D., 40 cm to detector). Calibration
      curves were constructed for celecoxib (0.2-0.6 mg/ml) by the internal standard
      method with 2-nitro aniline as an internal standard (coefficient of correlation
      greater than 0.999). The intermediate precision (between day precision) of
      migration times and peak area ratios of celecoxib to internal standard were 1.44
      and 1.58% R.S.D., demonstrates good reproducibility of the method. The method was
      applied to a commercial celecoxib formulation (Revibra, 100 mg) and the
      percentage recoveries were ranged from 93.0 to 98.4%.

PMID- 12008129
TI  - Imipramine hydrochloride and desipramine hydrochloride as new reagents for
      detection of microamounts of blood in urine.
AB  - Benzidine and o-tolidine, the hazardous carcinogens are still in use for the
      detection of blood in urine. Development of safer substitutes are of paramount
      importance. Unfortunately, the alternate available reagents lack specificity,
      sensitivity and reproducibility. Imipramine hydrochloride (IPH) and desipramine
      hydrochloride (DPH) are proposed as new reagents for the detection of blood in
      urine. Both the reagents impact to blood a green-blue to blue color, in the
      presence of acetic acid and hydrogen peroxide and the development of this color
      is explored under laboratory conditions. IPH or DPH compares favorably with
      benzidine and multistix methods. Both the reagents are relatively inexpensive,
      and have required sensitivity and stability. The proposed reagents offer
      advantages of relatively low sensitivity to endogenous vegetable peroxidases;
      hence, the test can be performed on samples taken from patients who are on a
      normal diet and the results are reproducible. Besides, the reagents, are non
      carcinogenic and can replace benzidine and o-tolidine without any extra
      procedural difficulties as they also exhibit a similar blue color.

PMID- 12008130
TI  - Determination of bopindolol in pharmaceuticals by capillary isotachophoresis.
AB  - Capillary isotachophoresis (ITP) with conductimetric detection has been used for
      separating and determining bopindolol (I) in commercial mass-produced
      pharmaceutical preparations. The optimised operational electrolyte system
      consisted of 5 mM potassium picolinate and 5 mM picolinic acid (leading
      electrolyte, LE; pH 5.37) and 10 mM formic acid as the terminating electrolyte
      (TE). The driving and detection currents were 50 microA (for 350 s) and 10
      microA, respectively. The single analysis took about 12 min. Under such
      conditions the effective mobility of I was determined as 16.73 10(-9)m(2) V(-1)
      s(-1) (with tetraethylammonium as the mobility standard). The calibration graph
      relating the ITP zone length to the concentration of I was rectilinear
      (r=0.99990) in the range 10-100 mg l(-1). The relative standard deviation
      (R.S.D.) was 0.90% (n=6) when determining 50 mg l(-1) of I in pure test solution.
      Sample pre-treatment of the tablets involved ice-cooled extraction of I with
      methanol. The method was suitable for determining I in Sandonorm tablets with
      R.S.D. value 1.45% (n=6). According to the validation procedure based on the
      standard addition method the recovery was 97.3%.

PMID- 12008131
TI  - LC determination of oxcarbazepine and its active metabolite in human serum.
AB  - Twenty-five percent of epileptic patients present refractory seizures to current
      frontline antiepileptic drugs, needing new treatments and leading to the
      introduction of several new AEDs, among which is oxcarbazepine (Trileptal). This
      10-ketoanalogue of carbamazepine seems to be a weaker inducer of cytochrome P450
      3A4. However, pharmacokinetic interactions with clinical significance have
      already been reported, before the marketing of Trileptal in France. The aim of
      this study was to develop and validate a HPLC method allowing simultaneous dosage
      of oxcarbazepine, 10-hydroxycarbamazepine, epoxycarbamazepine, carbamazepine,
      phenobarbital and phenytoin. After plasma defecation by acetonitrile, dosage was
      obtained by analysis of the supernatants on a C(18) reversed-phase column coupled
      with UV detection (240 nm). The statistical validation was performed according to
      the recommendations of a European technical commission. This method seems to
      provide a quite good selectivity from the psychotropic therapeutics, which is
      commonly coprescribed with AEDs. Linearity was established for the whole
      concentration range, whatever the compound. Quantization limits of oxcarbazepine,
      10-hydroxycarbamazepine, epoxycarbamazepine, carbamazepine, phenobarbital and
      phenytoin are 0.58, 3.5, 2.35, 0.66, 1.02 and 3.13 microg/ml, respectively, and
      absolute recoveries are 105.15, 84.76, 94.45, 96.52, 98.62 and 95.08%,
      respectively.

PMID- 12008132
TI  - Spectrophotometric determination of metronidazole and tinidazole in
      pharmaceutical preparations.
AB  - Sensitive and simple spectrophotometric methods for the determination of
      metronidazole (MNZ) and tinidazole (TNZ) in either pure form or in its
      pharmaceutical formulations are described. The first method is based on the
      interaction of 3-methylbenzothiazolin-2-one hydrazone (MBTH) with MNZ/TNZ
      (reduced drug) in presence of copper sulphate and pyridine in acidic medium. The
      resulting yellowish orange products have lambda(max) of 500 and 490 nm,
      respectively, for MNZ and TNZ and are stable for about 4 h. The second method
      describes the reaction between reduced diazotised drugs with N-(1
      naphthyl)ethylenediamine dihydrochloride (NEDA) in neutral medium to yield pink
      products which have lambda(max) of 520 and 505 nm, respectively, for MNZ and TNZ,
      respectively. The products are stable for more than 24 h. Common excipients used
      as additives in pharmaceutical preparations do not interfere in the proposed
      method. Both the methods are highly reproducible and have been applied to a wide
      variety of pharmaceutical preparations and the results compare favourably with
      those of official methods.

PMID- 12008133
TI  - Characterization of the similarity of chemical compounds using electrospray
      ionization mass spectrometry and multivariate exploratory techniques.
AB  - The applicability and usefulness of electrospray mass spectrometry to the
      analysis of a small data set of 52 synthetic substances to probe their molecular
      similarity/diversity has been demonstrated. The first stage was the reduction of
      the data by Principal Component Analysis (PCA), to visualize the structure of the
      data. Sequential Projection Pursuit (SPP) was applied to detect outlying objects.
      Hierarchical cluster analysis was employed to produce a dendrogram, using group
      average linkage clustering. Finally, the cluster results of spectral data were
      compared with that of structural fingerprints and an expert's classification by
      using the similarity measure of Wallace.

PMID- 12008134
TI  - Validation of a LC-fluorescence method for determination of free captopril in
      human plasma, using a pre-column derivatization reaction with monobromobimane.
AB  - Both derivatization of free captopril in human plasma samples using
      monobromobimane as fluorescent label and the corresponding HPLC-fluorescence
      detection (FLD) method were validated. Calibration curve for the fluorescent
      captopril derivative in plasma samples is linear in the ppb-ppm range with a
      detection limit of 4 ppb and an identification limit of 10 ppb (P%: 90; nu > or =
      5). These methods were successfully applied on bioequivalence studies carried out
      on some marketed pharmaceutical formulations.

PMID- 12008135
TI  - Sensitive LC determination of ciprofloxacin in pharmaceutical preparations and
      biological fluids with fluorescence detection.
AB  - A simple and highly sensitive isocratic reversed-phase high-performance liquid
      chromatographic method (RP-HPLC) has been developed for the determination of
      ciprofloxacin. Separation of ciprofloxacin and anthranilic acid (internal
      standard) was achieved on a Kromasil 100, C(18), 5 microm (250 x 4.6 mm i.d.)
      reversed-phase column, using fluorescence detection with lambda(exc)=300 nm and
      lambda(emi)=458 nm. The mobile phase consisted of acetonitrile-methanol-acetate
      buffer (pH 3.60; 0.05 M) (10:30:60 v/v/v) containing 1% v/v acetic acid. The
      analysis was performed in less than 9 min, with a flow rate of 0.8 ml min(-1). A
      rectilinear relationship was observed for concentrations between 0.005 and 1.0
      microg ml(-1) of ciprofloxacin in aqueous standard solutions and serum and the
      detection limit was 20 pg injected on-column. The intra- and inter-day relative
      standard deviation (n=8) ranged from 1.6 to 2.6% and from 1.9 to 4.8%,
      respectively, calculated at three concentration levels of standard solutions.
      Direct measurements of ciprofloxacin in pharmaceutical preparations and in serum,
      after precipitation of proteins, were performed with high precision and accuracy.
      The application of the method to urine samples involved a solid-phase extraction
      treatment of the samples using C(18) cartridges. The linear working range in
      urine extended from 0.05 to 2.0 microg ml(-1) and the detection limit was 0.2 ng
      injected on-column.

PMID- 12008136
TI  - Simultaneous determination of terbinafine HCL and triamcinolone acetonide by UV
      derivative spectrophotometry and spectrodensitometry.
AB  - A binary mixture of terbinafine hydrochloride and triamcinolone acetonide was
      determined by three different methods. The first one concerned with determination
      of both drugs using first derivative (D(1)) spectrophotometric technique at 297
      and 274 nm over concentration ranges of 5-30 and 4-24 microg ml(-1), with mean
      percentage accuracies 99.90+/-0.67 and 100.25+/-0.49, respectively. The second
      method depends on ratio-spectra 1st derivative (RSD(1)) spectrophotometry at 298
      and 248 nm over the same concentration ranges with mean percentage accuracies
      100.22+/-0.51 and 99.93+/-0.56, respectively. The spectrodensitometric analysis
      provides a rapid and precise method for the separation and quantitation of both
      terbinafine hydrochloride and triamcinolone acetonide. The method depends on the
      quantitative densitometric evaluation of thin layer chromatogram of terbinafine
      hydrochloride and triamcinolone acetonide at 283 and 238 nm over concentration
      ranges of 5-25 and 2.5-22.5 microg spot(-1), with mean percentage accuracies
      100.66+/-0.51 and 100.27+/-0.73, respectively. The suggested procedures were
      checked using laboratory prepared mixtures and were successfully applied for the
      analysis of their pharmaceutical preparations. The three methods retained their
      accuracy and precision when applying the standard addition technique. The results
      obtained by applying the proposed methods were statistically analysed and
      compared with those obtained by a reported method.

PMID- 12008137
TI  - Application of the artificial neural network in quantitative structure-gradient
      elution retention relationship of phenylthiocarbamyl amino acids derivatives.
AB  - Quantitative structure-retention relationship(QSRR) method was used to model
      reversed-phase high-performance liquid chromatography (RP-HPLC) separation of 18
      selected amino acids. Retention data for phenylthiocarbamyl (PTC) amino acids
      derivatives were obtained using gradient elution on ODS column with mobile phase
      of varying acetonitrile, acetate buffer and containing 0.5 ml/l of triethylamine
      (TEA). Molecular structure of each amino acid was encoded with 36 calculated
      molecular descriptors. The correlation between the molecular descriptors and the
      retention time of the compounds in the calibration set was established using the
      genetic neural network method. A genetic algorithm (GA) was used to select
      important molecular descriptors and supervised artificial neural network (ANN)
      was used to correlate mobile phase composition and selected descriptors with the
      experimentally derived retention times. Retention time values were used as the
      network's output and calculated molecular descriptors and mobile phase
      composition as the inputs. The best model with five input descriptors was chosen,
      and the significance of the selected descriptors for amino acid separation was
      examined. Results confirmed the dominant role of the organic modifier in such
      chromatographic systems in addition to lipophilicity (log P) and molecular size
      and shape (topological indices) of investigated solutes.

PMID- 12008138
TI  - Simultaneous spectrophotometric determination of chlorphenoxamine hydrochloride
      and caffeine in a pharmaceutical preparation using first derivative of the ratio
      spectra and chemometric methods.
AB  - Three new methods are described for the simultaneous determination of
      chlorphenoxamine hydrochloride (CP) and caffeine (CAF) in their combination. In
      the first method, ratio spectra derivative spectrophotometry, analytical signals
      were measured at the wavelengths corresponding to either maxima and minima for
      both drugs in the first derivative spectra of the ratio spectra obtained by using
      each other spectra as divisor in their solution in 0.1 M HCl. In the other two
      methods, chemometric techniques, classical least-squares (CLS) and inverse least
      squares (ILS), the concentration data matrix were prepared by using the synthetic
      mixtures containing these drugs in 0.1 M HCl. The absorbance data matrix
      corresponding to the concentration data matrix was obtained by the measurements
      of absorbances in the range 225-285 nm in the intervals with Deltalambda = 5 nm
      at 13 wavelengths in their zero-order spectra, then, calibration or regression
      was obtained by using the absorbance data matrix and concentration data matrix
      for the prediction of the unknown concentrations of CP and CAF in their mixture.
      The numerical values were calculated by using MAPLE V software in chemometric
      methods. The procedures do not require any separation step. The accuracy and the
      precision of the methods have been determined and they have been validated by
      analyzing synthetic mixtures containing title drugs. These three methods were
      successfully applied to a pharmaceutical formulation, sugar-coated tablet, and
      the results were compared with each other.

PMID- 12008139
TI  - Electrospray LC-MS/MS quantitation, stability, and preliminary pharmacokinetics
      of bradykinin antagonist polypeptide B201 (NSC 710295) in the mouse.
AB  - B201 (NSC 710295), [SUIM-(Darg-Arg-Pro-Hyp-Gly-Igl-Ser-Digl-Oic-Arg)(2)], a third
      generation of bradykinin (BK) antagonist, has been found to possess high potency.
      We report the development of a highly sensitive electrospray LC-MS/MS assay
      method for the analysis of B201 in plasma for the first time, using an ion-trap
      mass spectrometer. Human or mouse plasma (0.2 ml) was spiked with B201 and the
      internal standard, substance P. The compounds were extracted with a
      preconditioned C-18 reversed-phase column and analyzed by LC-MS/MS. The analytes
      were separated on a 50 x 2 mm (i.d.) BetaBasic C8 column, using a gradient
      elution. The positive ion selected reaction monitor mode was used monitoring the
      transitions of ions at m/z 938.9(3+)-->816.0(2+) for B201 and 674.3(2+)-
      >665.7(2+) for substance P. Assay validation was performed, and the limit of
      quantitation (LOQ) for B201 was found to be 1 ng/ml for human plasma and 2.5
      ng/ml for mouse plasma. The recovery was 78% for B201 and 88% for substance P.
      The assay was linear from 2.5 to 1500 ng/ml for mouse plasma monitored. Using a
      0.2 ml plasma, the within-day CVs were 9.3% at 2.5 ng/ml, 6.5% at 100 ng/ml, and
      3.8% at 1000 ng/ml for human plasma (n=6). For mouse plasma, the respective
      within-day CVs were 17.6, 9.6, and 6.2% (n=6). The between-day CVs for human
      plasma were 8.2, 10.9, and 2.4%, respectively, (n=3) and the respective values
      for mouse plasma were 11.9, 8.6 and 6.5% (n=6). Pharmacokinetics of B201 in the
      mouse was studied following i.v. administration at 5 mg/kg and found to conform
      to a two-compartment model with an initial half-life of 14 min and a terminal
      half-life of 44 h. Plasma B201 peak level was detected at microg/ml range and the
      levels were detectable for a least 24 h. Preliminary oral bioavailability was
      found to be about 1%. This method demonstrates that an ion trap mass spectrometer
      can be a powerful tool to quantify large peptides at low nanogram per milliliter
      with a non-isotopically labeled internal standard.

PMID- 12008140
TI  - Polarographic determination of phenytoin and benzophenone (as impurity) in
      pharmaceutical preparations.
AB  - A differential pulse polarographic method is described for detection and trace
      determination of benzophenone (the main impurity) in phenytoin powder. The method
      depends upon the polarographic activity of benzophenone in Britton-Robinson
      buffer pH 5.6. The limit of detection was found to be 2.5 x 10(-6) microg ml(-1).
      Phenytoin has been analysed polarographically after oxidation with alkaline
      permanganate to give benzophenone; the limit of detection was found to be 6 x 10(
      6) microg ml(-1).

PMID- 12008141
TI  - Determination of flavonoids in Semen Cuscutae by RP-HPLC.
AB  - Flavonoids contents in 40 samples of Semen Cuscutae collected from areas all
      around China were investigated. Five principal flavonoids, quercetin 3-O-beta-D
      galactoside-7-O-beta-D-glucoside, quercetin 3-O-beta-D-apiofuranosyl-(1-->2)-beta
      D-galactoside, hyperoside, quercetin and kaempferol were analyzed simultaneously
      by using a reversed phase liquid chromatograph system with 0.025 M phosphoric
      acid-methanol as mobile phase. The recovery of the method was 97.0-102.9%, and
      all the flavonoids showed good linearity (r > or = 0.9990) in a relatively wide
      concentration range. The results indicated that contents of flavonoids in S.
      Cuscutae varied significantly from species to species, locality to locality, and
      parasiting host to host. Cuscuta australis contained a much higher content of
      kaempferol than C. chinensis, and few flavonoids were detected in C. japonica.
      The quality of S. Cuscutae can be evaluated according to the contents of
      flavonoids.

PMID- 12008142
TI  - Determination of betamethasone disodium phosphate in the in vitro media of PLGA
      microspheres by high-performance liquid chromatography.
AB  - Betamethasone disodium phosphate is a kind of corticosteroid, which is commonly
      used in the intralesional treatment of keloids. In this work, polymeric
      microspheres loaded with betamethasone disodium phosphate were fabricated to
      design a sustained-release system. A validated HPLC technique for determination
      of betamethasone disodium phosphate in in vitro media of the polymeric
      microspheres has been developed. The operation conditions were optimized. The
      analytical column was ZORBAX Bonus-RP column with 4.6 x 150 mm ID and a particle
      size of 5 microm. The mobile phase consisted of acetonitrile-0.01% phosphoric
      acid water solution (40:60, v/v). The flow rate was 1.0 ml/min and injection
      volume was 50 microl. The elutes were detected at 240 nm. Linearity,
      repeatability, inter- and intra-assay precision and accuracy of the method were
      evaluated. The liner range was obtained in a concentrated range of 20-1000
      microg/ml, with a coefficient of correlation r=0.999978. The limit of detection
      for betamethasone disodium phosphate in the in vitro test samples was 0.25
      microg. Recovery of betamethasone disodium phosphate from the in vitro test
      samples was 99.7+/-5.2% (mean+/-SD). Stability of betamethasone disodium
      phosphate at different pH values and temperatures were also investigated.

PMID- 12008143
TI  - High performance liquid chromatographic assay for the quantitation of total
      glutathione in plasma.
AB  - A simple and widely used homocysteine HPLC procedure was applied for the HPLC
      identification and quantitation of glutathione in plasma. The method, which
      utilizes SBDF as a derivatizing agent utilizes only 50 microl of sample volume.
      Linear quantitative response curve was generated for glutathione over a
      concentration range of 0.3125-62.50 micromol/l. Linear regression analysis of the
      standard curve exhibited correlation coefficient of 0.999. Limit of detection
      (LOD) and limit of quantitation (LOQ) values were 5.0 and 15 pmol, respectively.
      Glutathione recovery using this method was nearly complete (above 96%). Intra
      assay and inter-assay precision studies reflected a high level of reliability and
      reproducibility of the method. The applicability of the method for the
      quantitation of glutathione was demonstrated successfully using human and rat
      plasma samples.

PMID- 12008144
TI  - Single-step extraction of fluconazole from plasma by ultra-filtration for the
      measurement of its free concentration by high performance liquid chromatography.
AB  - High performance liquid chromatography (HPLC) is the reference method for
      measuring concentrations of antimicrobials in blood. This technique requires
      careful sample preparation. Protocols using organic solvents and/or solid
      extraction phases are time consuming and entail several manipulations, which can
      lead to partial loss of the determined compound and increased analytical
      variability. Moreover, to obtain sufficient material for analysis, at least 1 ml
      of plasma is required. This constraint makes it difficult to determine drug
      levels when blood sample volumes are limited. However, drugs with low plasma
      protein binding can be reliably extracted from plasma by ultra-filtration with a
      minimal loss due to the protein-bound fraction. This study validated a single
      step ultra-filtration method for extracting fluconazole (FLC), a first-line
      antifungal agent with a weak plasma-protein binding, from plasma to determine its
      concentration by HPLC. Spiked FLC standards and unknowns were prepared in human
      and rat plasma. Samples (240 microl) were transferred into disposable microtube
      filtration units containing cellulose or polysulfone filters with a 5 kDa cut
      off. After centrifugation for 60 min at 15000g, FLC concentrations were measured
      by direct injection of the filtrate into the HPLC. Using cellulose filters, low
      molecular weight proteins were eluted early in the chromatogram and well
      separated from FLC that eluted at 8.40 min as a sharp single peak. In contrast,
      with polysulfone filters several additional peaks interfering with the FLC peak
      were observed. Moreover, the FLC recovery using cellulose filters compared to
      polysulfone filters was higher and had a better reproducibility. Cellulose
      filters were therefore used for the subsequent validation procedure. The
      quantification limit was 0.195 mgl(-1). Standard curves with a quadratic
      regression coefficient > or = 0.9999 were obtained in the concentration range of
      0.195-100 mgl(-1). The inter and intra-run accuracies and precisions over the
      clinically relevant concentration range, 1.875-60 mgl(-1), fell well within the
      +/-15% variation recommended by the current guidelines for the validation of
      analytical methods. Furthermore, no analytical interference was observed with
      commonly used antibiotics, antifungals, antivirals and immunosuppressive agents.
      Ultra-filtration of plasma with cellulose filters permits the extraction of FLC
      from small volumes (240 microl). The determination of FLC concentrations by HPLC
      after this single-step procedure is selective, precise and accurate.

PMID- 12008145
TI  - A validated high-performance liquid chromatographic method for the determination
      of glibenclamide in human plasma and its application to pharmacokinetic studies.
AB  - Glibenclamide is a potent second generation oral sulfonylurea antidiabetic agent
      widely used for the treatment of type II diabetes melitus. A rapid, sensitive,
      precise, accurate and specific HPLC assay for the determination of glibenclamide
      in human plasma was developed and validated. After addition of flufenamic acid as
      internal standard, the analytes were isolated from human plasma by liquid-liquid
      extraction. The method was linear in the 10-400 ng/ml concentration range (r >
      0.999). Recovery for glibenclamide was greater than 91.5% and for internal
      standard was 93.5%. Within-day and between-day precision, expressed as the
      relative standard deviation (RSD%), ranged from 1.4 to 5.9% and 5.8 to 6.6%,
      respectively. Assay accuracy was better than 93.4%. The assay was used to
      estimate the pharmacokinetics of glibenclamide after oral administration of a 5
      mg tablet of glibenclamide to 18 healthy volunteers.

PMID- 12008146
TI  - Evaluation of the excretion and metabolism of the new analgesic agent RWJ-22757
      in male and female CR Wistar rats.
AB  - The excretion and metabolism of (+/-)-trans-3-(2-bromophenyl)octahydroindolizine
      hydrochloride (RWJ-22757) have been investigated in male and female CR Wistar
      rats. Radiolabeled [14C] RWJ-22757 was administered orally to each of the rats as
      a single 60 mg/kg suspension dose. Plasma (0-48 h), urine (0-168 h) and fecal (0
      168 h) samples were collected and analyzed. There were no significant gender
      differences observed in the data. The estimated elimination half-life of the
      total radioactivity from plasma was 19 h while the estimated elimination half
      life of RWJ-22757 was 15 h. Recoveries of total radioactivity in urine and feces
      were 58.4+/-5.8 and 42.4+/-6.3%, respectively. RWJ-22757 and a total of 11
      metabolites were isolated in rat plasma, urine, and fecal extracts. The
      structures of four of these metabolites were tentatively identified. Unchanged
      RWJ-22757 accounted for < 4% of the dose in plasma and urine and 28% in feces;
      thus, indicating the drug was extensively metabolized and either not absorbed
      well or biliary excreted. Identified metabolites accounted for > 80% of the total
      radioactivity contained in the samples. The following pathways were used to
      describe the formation of the metabolites identified in rats: octahydroindolizine
      ring oxidation, phenyl hydroxylation, octahydroindolizine ring oxidation followed
      by ring opening to a carboxylic acid function and octahydroindolizine ring
      oxidation followed by ring opening and N-methylation.

PMID- 12008147
TI  - Static headspace gas chromatographic analysis of the residual solvents in gel
      extrusion module tablet formulations.
AB  - A rapid static headspace-gas chromatographic (SHS-GC) method was developed and
      validated for the quantitation of residual solvents in pharmaceutical gel
      extrusion module (GEM) tablet formulations. A static headspace sampling technique
      was utilized to overcome the difficulties imposed by direct injection methods. A
      Rtx-1701 megabore capillary column was selected to achieve optimal resolution
      among organic volatile chemicals used commonly in the manufacturing of GEM
      tablets, residual solvents in the active ingredient and excipients, and other
      formulation matrix artifacts. A 50-mM pH 3.0 sodium phosphate buffer was used as
      a sample diluent to minimize matrix effects. The instrumental parameters of the
      SHS-GC method were optimized for sensitivity and precision. Quantitation was
      performed by external standard analysis. The SHS-GC method was validated
      according to regulatory requirements and produced acceptable results with respect
      to specificity, linearity, range, detection and quantitation limits, precision,
      and accuracy.

PMID- 12008148
TI  - Determination of picomole amounts of thiamine through flow-injection analysis
      based on the suppression of luminol-KIO(4) chemiluminescence system.
AB  - A continuous flow sensor for the determination of thiamine was constructed by
      using controlled-reagent-release technology in a FIA-CL system. The analytical
      reagents, luminol and KIO(4), were both immobilized on an anion-exchange column.
      The CL signal produced by the reaction between luminol and KIO(4), which were
      eluted from the column through H(2)O injection, was decreased in the presence of
      thiamine. The decreased CL intensity was linear with thiamine concentration in
      the range 3.3 pmol ml(-1)-6.7 nmol ml(-1); and the limit of detection was 1.0
      pmol ml(-1) (3.). The whole process, including sampling and washing, could be
      completed in 0.5 min with a relative standard deviation of less than 3.0%. The
      flow sensor showed remarkable stability and could be easily reused over 80 h. The
      sensor proposed was tested in determination of thiamine in pharmaceutical
      preparation and human urine samples.

PMID- 12008149
TI  - Stability of 5-acetamido-6-formylamino-3-methyluracil in buffers and urine.
AB  - The caffeine metabolite 5-acetamido-6-formylamino-3-methyluracil (AFMU) and its
      product of spontaneous deformylation 5-acetamido-6-amino-3-methyluracil (AAMU)
      were synthesized. Their ultraviolet absorption spectra differed significantly
      from each other and wavelengths of absorption maximum and molar extinction
      coefficients varied with pH. The changes of the absorption spectrum parameters of
      AFMU and AAMU with pH indicated that they ionized with pK(a) of 5.7 and 8.3,
      respectively. The spontaneous deformylation of AFMU in solutions of different pH
      and urine were investigated spectrophotometrically and by high-performance liquid
      chromatography. The data showed the following: (a) AFMU transformed uniquely to
      AAMU; (b) deformylation obeyed first-order kinetics under the different
      conditions tested; (c) the half-life of AFMU varied between 7.8 and 36 h between
      pH 9.0 and 2.0 at 24 degrees C, with a maximum of 150 h at pH 3.0; (d) AFMU
      deformylated below pH 2.0 and above pH 10.0 with a half-life of less than 4.6 h;
      (e) half-lives of AFMU in urine were 57 and 12.5 h at 24 and 37 degrees C,
      respectively, comparable to those in buffers at equivalent pH and temperature.
      The results are discussed in relation to the mechanism of deformylation and the
      use of caffeine as a probe drug for NAT2 phenotyping.

PMID- 12008150
TI  - Application of LC/MS/MS in the quantitation of SU101 and SU0020 uptake by
      3T3/PDGFr cells.
AB  - SU101 or leflunomide, has been studied extensively because of its anti-cancer and
      immunomodulating properties. The parent isoxazole compound is converted in vitro
      and metabolized in vivo to an open ring isomeric form, SU0020. Several
      pharmacological activities have been reported for the parent and metabolite
      compounds including inhibition of platelet-derived growth factor (PDGF)-mediated
      signaling for the parent compound and inhibition of de novo pyrimidine
      biosynthesis for the metabolite. The inhibition of PDGF-mediated signaling and
      the anti-tumor properties have been ascribed to the parent compound. In spite of
      its short plasma half-life of the parent molecule, SU101 can be administered
      intermittently in animal tumor models and retain efficacy. Therefore, the
      relationship between plasma levels of SU101 and its efficacy in tumor-implanted
      immuno-compromised mice is not well established. This study was conducted to
      assess the concentration of SU101 in 3T3/PDGFr alpha and beta cells (NIH3T3 mouse
      fibroblasts engineered to overexpress human PDGFr alpha or beta) to better
      understand the cellular levels of SU101 and SU0020. Two strains of 3T3/PDGFr
      cells (alpha and beta) were incubated with 1, 25, and 100 microM concentrations
      of SU101 for 1, 6, 24, and 48 hours. Quantitation of SU101 and SU0020 in these
      cell lines was achieved by a specific and sensitive liquid chromatography-tandem
      mass spectrometry (LC/MS/MS) method. Interestingly, in both alpha and beta cell
      lysates SU101 was much more concentrated than SU0020. The greater concentration
      of SU101 versus SU0020 that was observed may be due to the preferential
      partitioning of SU101 into the cells and this shows that significant levels of
      the parent drug can reach the pharmacological site of action for inhibition of
      PDGF receptors. The data suggest that the conversion of SU101 to SU0020 is much
      slower in these cells than in the incubation media.

PMID- 12008151
TI  - LC and TLC determination of cinnarizine in pharmaceutical preparations and serum.
AB  - New high performance liquid chromatography (HPLC) and thin layer densitometry
      (TLC) methods are developed for quantification of cinnarizine in dosage forms in
      the presence of its photo-degradation products and related substances and in the
      presence of its metabolites in serum. Mobile phases consisting of benzene
      methanol-formic acid (80:17:3) and methanol-acetate buffer of pH 4 (70:30) are
      satisfactorily used for resolution of cinnarizine from associated substances by
      TLC and HPLC techniques, respectively. The lower detection limits are 16 and 10
      ng microl(-1) of cinnarizine with standard deviations of 1.3 and 1.1% with TLC
      and HPLC, respectively. The methods are used for assessment of drug purity,
      stability, bioavailability, bioequivalency and tablet dissolution rate. Four
      cinnarizine related substances and six drug degradation products are isolated and
      identified by infrared and mass spectrometry. The results obtained by both
      techniques are in good agreement and offer the advantages of reproducibility and
      accuracy.

PMID- 12008152
TI  - Determination of triamterene by transitory retention in a continuous flow solid
      phase system with fluorimetric transduction.
AB  - A rapid and simple flow-through solid phase espectrofluorimetric system (sensor)
      is described in this paper for the determination of the diuretic triamterene at
      ng ml(-1) level in physiological fluids and in pharmaceuticals. This sensor is
      based on the transitory retention of the analyte on the cationic ion-exchanger
      gel Sephadex SP C-25 placed into a quartz flow-cell in the detection zone itself
      of a spectrofluorimeter and the continuous monitorization of its intrinsic
      fluorescence. The spectrofluorimeter was tuned at 240 (excitation) and 440 nm
      (emission). A transitory signal was obtained because the carrier solution used
      also eluted the analyte from the sensing zone and no derivatization reactions
      were needed. Triamterene could be determined in the concentration ranges of 10
      400 and 2.5-80 ng ml(-1) with detection limits of 0.95 and 0.17 ng ml(-1) for 300
      and 1000 microl of sample volume, respectively. The relative standard deviations
      (RSD) for ten independent determinations and at three concentration levels of
      standards solutions were lower than 0.90 for 300 microl and 0.45 for 1000 microl.
      The RSDs for the determination of triamterene in serum samples and
      pharmaceuticals were lower than 3.3 and 2.6%, respectively. The method was
      satisfactorily applied to the determination of triamterene in human serum and
      pharmaceuticals.

PMID- 12008153
TI  - Determination of 11-keto-boswellic acid in human plasma.
AB  - A sensitive, specific, accurate, fast and reproducible GC/MS-method for the
      quantitative determination of 11-keto-boswellic acid in human plasma using
      18alpha-glycyrrhetinic acid as the internal standard was developed and validated.
      11-Keto-boswellic acid and the internal standard were separated from acidified
      plasma by liquid/liquid extraction. The extracted samples were methylated and
      analyzed by GC/MS in the negative ion chemical ionization mode (NICI) and
      selected ion monitoring (SIM). The total run time was 8 min between injections.
      The assay described in this paper demonstrates a validated lower limit of
      quantification of 0.0100 microg/ml using 1 ml of plasma. The calibration curves
      are linear in the measured range between 10.0 and 2000 ng/ml plasma. The overall
      precision (expressed as CV) and accuracy (expressed as bias) for all
      concentrations of quality controls and standards is better than 15%. No
      indications were found for possible instabilities of 11-keto-boswellic acid in
      plasma, in whole blood, in the extraction solvent or after repeated
      thawing/freezing cycles. The recovery of the extraction method is calculated as
      84%. The assay was applied successfully to determine the plasma level of 11-keto
      boswellic acid in a clinical pilot study.

PMID- 12008154
TI  - Determination of celecoxib in pharmaceutical formulations using UV
      spectrophotometry and liquid chromatography.
AB  - A new UV spectrophotometric method (UV method) and a reversed phase liquid
      chromatographic method (LC method) for the quantitative estimation of celecoxib,
      a selective COX-2 inhibitor, in pure form and in solid dosage form were developed
      in the present study. The linear regression equations obtained by least square
      regression method, were Abs=4.949 x 10(-2).Conc. (in microg/ml)+1.110 x 10(-2)
      for the UV method and Area under the curve=5.340 x 10(1).Conc. (in ng/ml)+3.144 x
      10(2) for the LC method, respectively. The detection limit, as per the error
      propagation theory, was found to be 0.26 microg/ml and 25 ng/ml, respectively,
      for the UV and LC methods. The developed methods were employed with a high degree
      of precision and accuracy for the estimation of total drug content in three
      commercial capsule formulations of celecoxib. The results of analysis were
      treated statistically, as per International Conference on Harmonisation (ICH)
      guidelines for validation of analytical procedures, and by recovery studies. The
      results were found to be accurate, reproducible and free from interference and
      better than the earlier reported methods.

PMID- 12008155
TI  - Voltammetric investigation of beta-estradiol.
AB  - Electrooxidation of beta-estradiol was investigated using a glassy carbon
      electrode (GCE) by cyclic voltammetry (CV), and differential pulse voltammetry
      (DPV). The statistical analysis of the linear relationships between concentration
      and peak current permits the quantitation of beta-estradiol by both CV and DPV in
      the concentration range of 4 x 10(-5)-10(-3) M with enough precision and
      accuracy. A mechanism was proposed about the electrooxidation of this substance.
      The methods were applied to a tablet form and a transdermal therapeutic system
      (TTS) of this drug. The results were statistically compared with those of
      official high performance liquid chromatography (HPLC) method and the differences
      were found as insignificant.

PMID- 12008156
TI  - Study on the inclusion complexes of bromazepam with beta- and beta-hydroxypropyl
      cyclodextrins.
AB  - Solubility enhancement of the water insoluble bromazepam was studied during the
      formation of its inclusion complexes with beta-cyclodextrin (beta-CD) and beta
      hydroxypropyl-cyclodextrin (beta-HP-CD). The phase solubility technique
      established by Higuchi and Connors and UV-spectrophotometric methods (zero- and
      second-order derivative approaches) were used to measure the changes introduced
      in this chemical system. The amount of time, which was necessary to reach
      equilibrium between inclusion complexes and their free components, was estimated
      and found equal to 24 h. The study was carried out at (i) pH 7.0 and 25 degrees C
      and (ii) pH 7.4 and 37 degrees C. The solubility of bromazepam increased linearly
      as a function of concentration for both beta-and beta-hydroxypropyl
      cyclodextrins. Thus, the phase solubility diagrams were classified as of A(L)
      type in all cases. Under the above-mentioned conditions, the formation constants
      of the inclusion complexes were calculated and their stoichiometry was evaluated,
      found in the range of 69-85 M(-1) and 1:1, respectively.

PMID- 12008157
TI  - LC determination of flavonoids: separation of quercetin, luteolin and 3-O
      methylquercetin in Achyrocline satureioides preparations.
AB  - The pharmacological activities of the flavonoids show the interest in quantifying
      these constituents in phytopharmaceutical preparations, as well as in the
      validation of the analytical methodologies. LC methods have been reported to
      quantify isolated flavonoids or these compounds in complex biological matrices,
      such as herbal raw materials and extractive preparations. This work was designed,
      therefore, to develop an LC system to separate quercetin, luteolin and 3-O
      methylquercetin and to quantify them in extractive solutions from Achyrocline
      satureioides. The main validation parameters of the method are also determined.
      The method showed linearity for quercetin and luteolin in the range 1-10
      microg/ml. The aqueous and ethanol 80% extractive solutions showed linear
      response in the range 2.5-20 microl/ml and ethanol 40% extractive solution in the
      range 2.5-10 microl/ml. Precision and accuracy were determined for ethanol 80%
      extractive solution, in the concentration of 10 microl/ml. The LC method showed
      an excellent performance in separating the flavonoids quercetin, luteolin and 3-O
      methylquercetin in A. satureioides extracts, since the presence of interference
      has been previously evaluated.

PMID- 12008158
TI  - Spectrophotometric multicomponent resolution of a veterinary formulation
      containing oxfendazole and oxyclozanide by multivariate calibration-prediction
      techniques.
AB  - Four multivariate calibration-prediction techniques, classical least-squares,
      inverse least-squares, principal component regression and partial least-squares
      regression were applied to the spectrophotometric multicomponent analysis of a
      veterinary formulation containing oxfendazole (OXF) and oxyclozanide (OXC)
      without any separation step. The multivariate calibrations were constructed by
      measuring the absorbance values at 14 points in the 285-350 nm wavelength range
      and by using the training set of standard mixtures containing OXF and OXC in the
      different compositions. The validity of building multivariate calibrations was
      checked by using the synthetic mixtures of both drugs. The multivariate
      calibration models were successfully applied to the spectrophotometric
      determination of OXF and OXC in laboratory prepared mixtures and a veterinary
      formulation. The results obtained were statistically compared with each other.

PMID- 12008159
TI  - Determination of lacidipine from urine by HPTLC using off-line SPE.
AB  - A simple, rapid and sensitive high performance thin layer chromatographic method
      was developed and validated for the estimation of lacidipine. The sample
      preparation involved protein precipitation followed by an efficient solid phase
      extraction on C18 cartridge. The analytes were isolated from 1 ml of urine and
      recovered by pure ethyl acetate solution. The method employed TLC aluminium plate
      precoated with silica gel 60F254 as the stationary phase. The solvent system
      employed consists of toulene-ethyl acetate [6.5:3.5v/v]. This system gave a dense
      and compact spot of the drug at R(f) value of 0.45. The linear regression data
      for the calibration plots showed good linear relationship (r=0.999) over the
      concentration range 10-80 ng. Recovery studies were performed at two different
      levels. The recovery data reveals that the R.S.D. for intra-day and inter-day
      analysis at 10 ng was found to be 0.84 and 0.22%, respectively. The proposed
      method was found to be useful for the routine analysis of pharmaceuticals and
      pharmacokinetic studies in human urine samples.

PMID- 12008160
TI  - Calcitonin in osteoporosis.

PMID- 12008161
TI  - Analgesic effect of calcitonin in osteoporosis.
AB  - Bone pain is the most common symptom in osteoporotic patients. To date, there is
      mounting evidence that calcitonin significantly reduces bone pain in
      osteoporosis, and that the analgesic effect can be evident as soon as the second
      week of treatment. The limitations to the use of calcitonin, which are parenteral
      administration and side effects, can now be overcome by the availability of the
      nasal spray preparation. At present, controlled studies have demonstrated the
      analgesic activity of calcitonin given by nasal spray in patients with vertebral
      crush fractures and bone pain. The mechanism for the analgesic effect of
      calcitonin is yet to be clarified. In humans, similarities between calcitonin and
      morphine-induced analgesia, and reports of calcitonin-induced elevation of plasma
      beta-endorphin levels, suggest the possible involvement of the endogenous opiate
      system in mediating the analgesic action of calcitonin. However, the
      demonstration of calcitonin binding sites in areas of the brain involved in pain
      perception and a series of animal studies have raised the possibility that
      calcitonin may directly modulate nociception in the central nervous system. In
      support of this hypothesis are some observations of an analgesic effect obtained
      by direct epidural or subaracnoidal injection of calcitonin in humans.

PMID- 12008162
TI  - Analgesic effects of calcitonin.
AB  - The analgesic activity of salmon calcitonin (subcutaneous or intranasal) has been
      demonstrated in several prospective clinical trials, in patients suffering
      different painful skeletal conditions, including recent nontraumatic osteoporotic
      vertebral fractures. The mechanism of the analgesic effect of calcitonin is not
      clear. It is possible that specific binding sites for salmon calcitonin exist in
      the brain. Another explanation is that changes in descending serotonergic
      modification on the sensory transmission mediated by C afferents contribute to
      the analgesic effects of calcitonin on pain in osteoporotic patients. From the
      clinical point of use, the analgesic effect of calcitonin is beneficial
      throughout the whole period of medical treatment of osteoporotic patients. Salmon
      calcitonin in a daily dose of 100 IU subcutaneously or 200 IU intranasally
      reduces dramatically the back pain (p < 0.0005) after a recent osteoporotic
      vertebral fracture, and promotes the early mobility of patients. The finding that
      injectable or intranasally administered salmon calcitonin effectively controls
      severe pain in osteoporotic patients with a recent vertebral fracture, allowing
      them earlier mobility in combination with a reduction of the urinary
      hydroxyproline excretion, and a limitation of the considerable bone loss that may
      occur during prolonged bed rest, make this therapeutic scheme attractive.

PMID- 12008163
TI  - Calcitonin for the long-term prevention and treatment of postmenopausal
      osteoporosis.
AB  - Calcitonin is a powerful inhibitor of osteoclast activity that exerts a rapid,
      transient, and reversible inhibition of bone resorption. Prolonged administration
      of parenteral calcitonin, by injections of 100 IU every 1 or 2 days, can prevent
      postmenopausal or postovariectomy bone loss, and is also able to increase
      trabecular bone mass among patients presenting an established osteoporosis.
      Prolonged treatment with calcitonin injections is, however, difficult to maintain
      over the long run. In addition to the ease of administration compared with the
      injectable forms, nasal calcitonin is much better tolerated, the side effects
      being rare and generally negligible. A prolonged administration of 200 IU
      intranasal calcitonin acutely inhibits parameters of bone resorption and can
      increase lumbar spine bone mineral density (BMD) by 1.7%-3.3% after 1 year. Lower
      doses also appear to be efficient to prevent early postmenopausal bone loss, but
      the data are conflictual. The results are more consistent in patients who already
      suffer from established osteoporosis. The increase in lumbar spine BMD is in the
      order of 1%-2% after 1 year with 200 IU daily. A therapeutic benefit of
      calcitonin at the level of the cortical bone has been less well demonstrated than
      for the trabecular bone. As for other antiosteoporotic therapies, the effect of
      calcitonin on the reduction of fracture risk has been examined less than the
      beneficial effect on trabecular bone mass. Currently, there is still no
      prospective, placebo-controlled study with a sufficient number of patients that
      demonstrates that long-term parenteral calcitonin administration reduces the risk
      of osteoporotic fractures. The efficacy of nasal calcitonin treatment to reduce
      vertebral fracture rate has been best examined in the PROOF (Prevent Recurrence
      of Osteoporotic Fractures) study. This was a prospective 5-year, placebo
      controlled, dose-response study of nasal calcitonin (100, 200, or 400 IU daily).
      The increase in lumbar spine BMD was modest but significant and not clearly dose
      dependent, as was the reduction in bone turnover. The relative risk of developing
      new vertebral fractures was reduced by 33% at the end of the study in the 200-IU
      dose group (relative risk = 0.67, 95% CI 0.47-0.97, p = 0.03). There was also a
      nonsignificant reduction in the risk of hip fracture in this dose group. The
      doses of 100 and 400 IU of calcitonin also reduced the vertebral fracture risk,
      but the difference did not reach the classical level of statistical significance.
      A possible effect of calcitonin to enhance bone quality, which cannot be assessed
      by routinely available methods, is currently being investigated in a prospective
      placebo-controlled trial that could provide a rational explanation for these
      effects of calcitonin on the reduction in the vertebral fracture rate without
      much increase in bone mass or a marked reduction in bone turnover.

PMID- 12008164
TI  - Possible mechanisms of the analgesic action of calcitonin.
AB  - The analgesic activity of calcitonin is well established, both through clinical
      observation and specific experimental investigation. The mechanism involved,
      however, is still unclear, and the hypotheses that have been proposed range from
      a simple peripheral antiinflammatory action to a direct action on specific
      receptors in the central nervous system. The various hypotheses are briefly
      reviewed and some of the supporting evidence is presented. The conclusion is that
      the principal mechanism of calcitonin's analgesic effect is probably a direct
      central action, but that this is further supported by peripheral mechanisms that
      may also improve bone status locally.

PMID- 12008165
TI  - Calcitonin in reflex sympathetic dystrophy syndrome and other painful conditions.
AB  - Salmon calcitonin (especially intranasal) provides an interesting analgesic
      effect in a series of painful conditions including reflex sympathetic dystrophy
      syndrome, adhesive capsulitis, ankylosing spondylitis, rheumatoid arthritis,
      vertebral crush fractures and metastasis, phantom limb pain, etc. In addition, in
      preliminary series, calcitonin shows an unexpected benefit to vasomotor changes
      and peptic ulcer. Yet the experience in these conditions is limited and needs
      confirmation. By comparison with the injectable, the intranasal route seems
      particularly interesting because of less undesirable effects, and a more rapid
      and probably more powerful analgesia.

PMID- 12008166
TI  - Frequency of abrupt vessel closure and side branch occlusion after percutaneous
      coronary intervention in a 6.5-year period (1994 to 2000) at a single medical
      center.
AB  - The aims of this study were to analyze the contemporary trends in the changing
      incidence of abrupt vessel closure (AVC) after percutaneous coronary intervention
      (PCI), to determine the impact of intracoronary stenting and glycoprotein
      IIb/IIIa inhibitors (GPIs) on complication rates and etiologies, and to determine
      the incidence of side branch occlusion (SBO) as the etiology of AVC in the stent
      era, complications occurring during 3,300 consecutive PCIs performed from April
      1994 to December 2000 at a single referral institution. In this consecutive
      patient cohort of PCI cases collected over a 6.5-year period, AVC occurred in 103
      of 3,300 cases (3.12%). Linear regression analysis over this time frame
      documented a steadily decreasing incidence of AVC from 5.9% in 1994 to 1.1% in
      2000 (-0.76%/per year, 95% confidence interval -0.99 to 0.52, p <0.05). Analysis
      using Pearson's correlation showed that the decreasing incidence of AVC was
      inversely correlated with the increasing percentage of intracoronary stents
      placed over this time period (r = -0.94, p <0.001). Additionally, GPI use
      increased from 0% in 1995 to 36.0% in 2000 (p = 0.009). The absolute incidence of
      SBO of a major branch vessel remained relatively stable over this 6.5-year
      period. However, SBO appeared to be increasing as the etiology of AVC, and
      accounted for 9.0% of AVC in 1995 compared with 28.0% of AVC in 2000. This
      increasing trend of the percentage of SBO as the etiology of AVC appeared to
      correlate with the increased use of stents (r = 0.85, p = 0.015). Thus, the
      incidence of AVC steadily decreased over the 6.5-year time period, and was
      associated with the increased use of stents and GPIs; conversely, SBO accounted
      for an increasing percentage of AVC over this time period.

PMID- 12008167
TI  - Predictors of door-to-balloon delay in primary angioplasty.
AB  - In the treatment of acute myocardial infarction, delayed reperfusion therapy is
      associated with increased mortality. Predictors of delay have been described for
      fibrinolysis but not for primary percutaneous transluminal coronary angioplasty
      (pPTCA). Therefore, we studied 40,017 consecutive patients with acute myocardial
      infarction who underwent pPTCA in the National Registry of Myocardial Infarction
      between June 1994 and April 2000. Median door-to-balloon times were calculated,
      and factors independently associated with a delay of >120 minutes were determined
      by logistic regression. The median door-to-balloon time among all patients was
      111 minutes (interquartile range 84 to 152). The proportion of patients with a
      delay of >2 hours was greater among those aged > or = 65 years (49% vs 41%),
      women (50% vs 42%), patients with contraindications to fibrinolysis (60% vs 41%),
      and those without chest pain on admission (61% vs 43%, all p <0.0001). Delay was
      also more common with transfer from another hospital (87% vs 38%), with
      presentation outside the hours of 8 A.M. to 4 P.M. (51% vs 38%), and in hospitals
      performing <49 pPTCAs/year (47% vs 41%, all p <0.0001). The strongest independent
      predictor of delay was hospital transfer, along with non-daytime presentation and
      low-volume centers. Older age, female sex, and non-white race were weaker
      predictors. Both patient and hospital factors are associated with delay in pPTCA
      after presentation. These findings may help design treatment algorithms to
      minimize delay, thus improving the survival benefit of pPTCA. These results may
      also help design trials of combination reperfusion strategies.

PMID- 12008168
TI  - Comparison of clinical outcomes using stents versus no stents after percutaneous
      coronary intervention for proximal left anterior descending versus proximal right
      and left circumflex coronary arteries.
AB  - Previous studies have demonstrated that proximal left anterior descending (LAD)
      stenoses have higher rates of restenosis after angioplasty than stenoses in other
      coronary segments. Stenting strategies may reduce this high rate of LAD
      restenosis. The study population included 1,289 patients with proximal coronary
      artery stenoses treated with percutaneous coronary interventions (PCI) with or
      without stents for single-vessel coronary disease between 1994 and 1999. Patients
      were divided into 4 groups: non-stent PCI in the proximal LAD artery (n = 168),
      non-stent PCI in proximal right/circumflex artery (n = 217), stent in the
      proximal LAD artery (n = 364), and stent to proximal right/circumflex artery (n =
      540). Procedural success was higher in the stenting groups, but there were no
      significant differences in the major in-hospital events between the different
      lesion locations among the groups. At 1-year follow-up, there was no difference
      in mortality or myocardial infarction between the groups. There was no
      significant difference in the rate of target lesion revascularization (TLR) in
      the patients with proximal LAD stents compared with the patients with proximal
      right/circumflex coronary artery stents (10.1% vs 13.8%, p = 0.11). In the
      patients who did not receive stents with proximal narrowings, there was a
      significant increase in TLR in the LAD group compared with the right/circumflex
      group (21.1% vs 12.5%, p = 0.04). Thus, patients with proximal stenoses treated
      with non-stenting strategies have lower procedural success than those treated
      with stenting strategies; the patients with proximal LAD non-stent PCI have
      significantly higher rates of clinical restenosis than patients with proximal
      right and circumflex stenoses. A stenting strategy for proximal LAD stenoses
      appears to attenuate the differences of clinical restenosis noted after non-stent
      PCI.

PMID- 12008169
TI  - Optimal strategy for administering enoxaparin to patients undergoing coronary
      angiography without angioplasty for acute coronary syndromes.
AB  - The optimal strategy for administration of low molecular weight heparin in
      patients with acute coronary syndrome (ACS) undergoing coronary angiography
      without percutaneous coronary intervention remains unclear. We studied
      postangiographic vascular complications in 325 consecutive patients (210 men and
      115 women, mean age 63 years) with ACS undergoing diagnostic coronary angiography
      via a femoral approach followed by immediate sheath removal. At the time of
      angiography, 44 patients were on intravenous unfractionated heparin (UFH), 229 on
      subcutaneous enoxaparin, and 52 on no heparin. Enoxaparin was withheld on the
      morning of angiography in 181 of 229 patients: the no A.M. dose group. Vascular
      complications were audited, including hematoma development at angiographic
      puncture sites; these complications were considered significant if >25 cm(2).
      Major vascular complications requiring transfusion or surgical interventions were
      infrequent in all groups. Patients receiving enoxaparin on the morning of
      angiography had a twofold increase in significant hematoma rate compared with the
      no A.M. dose group (31% vs 16%; p = 0.015). The no A.M. dose group had hematoma
      rates similar to UFH (20%; p = NS) and no anticoagulation (13.5%; p = NS). No
      significant increase in ischemic episodes occurred as a result of withholding
      enoxaparin in the no A.M. dose group. We conclude that omission of enoxaparin on
      the morning of cardiac catheterization results in vascular complications rates
      comparable to that of UFH without precipitating rebound ischemia. This is a
      practical, safe strategy for patients with ACS undergoing coronary angiography,
      allowing early mobilization for most patients who do not proceed to immediate
      percutaneous coronary intervention.

PMID- 12008170
TI  - Assessment of viable tissue in Q-wave regions by metabolic imaging using single
      photon emission computed tomography in ischemic cardiomyopathy.
AB  - Chronic electrocardiographic Q waves are often believed to reflect irreversibly
      scarred, transmurally infarcted myocardium. The aim of this study was to evaluate
      whether residual viable tissue persists in dysfunctional myocardial regions
      related to chronic Q waves on the surface electrocardiogram. A total of 148
      patients with healed myocardial infarction and impaired left ventricular (LV)
      function with heart failure symptoms underwent electrocardiography and metabolic
      imaging using technetium (Tc-99m) tetrofosmin/F18-fluorodeoxyglucose (FDG) single
      photon emission computed tomography (SPECT). The left ventricle was divided into
      4 major regions to compare myocardial viability in regions with and without
      chronic Q waves on surface electrocardiography. According to FDG SPECT metabolic
      imaging, residual viable tissue persisted in a high proportion (61%) of
      dysfunctional myocardial regions with chronic Q waves. Regions with chronic Q
      waves were more often dysfunctional than regions without Q waves. Moreover,
      dysfunctional regions with chronic Q waves were less frequently viable compared
      with dysfunctional regions without Q waves on the electrocardiogram. This study
      demonstrates that chronic Q waves on electrocardiography do not necessarily imply
      irreversibly scarred myocardium. Residual viable tissue persists in a high
      proportion of dysfunctional ventricular regions according to FDG SPECT metabolic
      imaging.

PMID- 12008171
TI  - Relation of heart rate dynamics to the occurrence of myocardial ischemia after
      coronary artery bypass grafting.
AB  - Postoperative myocardial ischemia is a common finding after coronary artery
      bypass grafting (CABG) and is associated with an adverse short-term clinical
      outcome. The reasons and pathophysiologic background for the occurrence of
      ischemia after CABG are not well established. We tested the hypothesis that
      altered heart rate (HR) behavior precedes the onset of myocardial ischemic
      episodes in patients after CABG. Time-domain HR variability measurements, along
      with analysis of Poincare plots and fractal scaling analysis were assessed in 40
      CABG patients from 48-hour postoperative Holter recordings. Twenty patients
      experienced 195 ischemic episodes during the postoperative course. In the
      univariate analysis of HR variability measurements of the first postoperative day
      (POD), the increased ratio between the short-term (SD1) and long-term (SD2) HR
      variability analyzed from the Poincare plot and the decreased short- and
      intermediate-term fractal scaling exponents alpha(1) and alpha(2) were
      significantly associated with ischemia during the study period (p <0.01, p <0.05,
      and p <0.05, respectively). In the multivariate model, the increased SD1/SD2
      ratio of the first POD was the most powerful independent predictor of all
      possible confounding variables for the occurrence of postoperative ischemia
      (corresponding to a change of 0.15 U; odds ratio 2.2 and 95% confidence interval
      1.2 to 5.7; p <0.01). Altered HR dynamics have been associated with myocardial
      ischemic episodes in patients after CABG, suggesting that the autonomic nervous
      system has an important role in the pathogenesis of myocardial ischemia in the
      postoperative phase of CABG.

PMID- 12008172
TI  - Comparison of patients undergoing enhanced external counterpulsation and
      percutaneous coronary intervention for stable angina pectoris.
AB  - Enhanced external counterpulsation (EECP) has recently emerged as a treatment
      option for angina in selected patients suitable for revascularization with
      percutaneous coronary intervention (PCI). We compared baseline characteristics
      and 1-year outcome in 2 cohorts of PCI candidates presenting with stable
      symptoms: 323 patients treated with EECP in the International EECP Patient
      Registry (IEPR), and 448 NHLBI Dynamic Registry patients treated with elective
      PCI. Compared with patients receiving PCI, IEPR patients had a higher prevalence
      of many risk factors including prior PCI (53.0% vs 33.3%, p <0.001), prior
      coronary artery bypass grafting (42.1% vs 18.6%, p <0.001), prior myocardial
      infarction (56.4% vs 27.8%, p <0.001), history of congestive heart failure (16.8%
      vs 9.2%, p <0.01), and history of diabetes (37.9% vs 23.5%, p <0.001). Left
      ventricular ejection fraction was lower among IEPR patients (mean 50.3% vs 59.2%,
      p <0.001). At 1 year, survival was comparable in the 2 cohorts (98.7% IEPR vs
      96.8% PCI, p = NS), as were rates of coronary artery bypass grafting during
      follow-up (4.5% IEPR vs 5.7% PCI, p = NS). At 1 year, 43.7% of IEPR patients
      reported no anginal symptoms compared with 73.4% of Dynamic Registry patients (p
      <0.001). Rates of severe symptoms (Canadian Cardiovascular Society class III, IV,
      or unstable) at 1 year were 15.5% among IEPR patients and 9.5% in the Dynamic
      Registry (p = 0.02). PCI candidates suitable for and treated with EECP had 1-year
      major event rates comparable to patients receiving elective PCI. Although PCI was
      associated with substantially lower rates of 1-year symptoms, EECP may be a safe
      treatment option for selected patients with obstructive coronary disease.

PMID- 12008173
TI  - Comparison of cardiorespiratory fitness versus leisure time physical activity as
      predictors of coronary events in men aged < or = 65 years and > 65 years.
AB  - Both high peak oxygen consumption (VO(2)) and high levels of leisure time
      physical activity (LTPA) are associated with a reduced risk of cardiovascular
      morbidity and mortality. We examined the contributions of LTPA and peak VO(2) to
      the risk of coronary events (CEs) in healthy younger (< or = 65 years, n = 522)
      and older (>65 years, n = 167) men from the Baltimore Longitudinal Study of
      Aging. LTPA derived from self reports of time spent in 97 activities were
      converted into METs-minutes/24 hours and grouped into high (> or = 6 METs),
      moderate- (4 to 5.9 METs), and low-intensity LTPA (<4 METs). Cardiorespiratory
      fitness was determined by measuring peak VO(2) during a maximal treadmill
      exercise test. Over a mean follow-up of 13.4 +/- 6.3 years, CEs occurred in 63
      men. After accounting for coronary risk factors, proportional-hazards analyses
      showed a relative CE risk of 0.53 (p <0.0001) for a SD increase in peak VO(2) in
      younger men and 0.61 (p = 0.024) in older men, whereas total LTPA was unrelated
      to coronary risk in either age group. When the 3 LTPA intensity levels were
      substituted for total LTPA in the model, peak VO(2) remained the only predictor
      of events in younger men, whereas high-intensity LTPA (RR = 0.39 for tertile 3 vs
      tertiles 1 and 2, p = 0.016) and peak VO(2) (RR = 0.61/SD increase, p = 0.024)
      were of similar importance in older men. Thus, in healthy younger men, higher
      cardiorespiratory fitness but not LTPA predicts a reduced risk of coronary heart
      disease, independent of conventional risk factors. For older men, high-intensity
      LTPA and fitness appear to be of similar importance in reducing coronary risk.

PMID- 12008174
TI  - Relation of extent of nocturnal blood pressure decrease to cardiovascular
      remodeling in never-treated patients with essential hypertension.
AB  - The clinical significance of the extent of a decrease in nocturnal blood pressure
      (BP) and the resulting classification of hypertensives as "dipper" (decrease in
      BP >10% day BP) or "nondipper" (decrease in BP <10% day BP) has been questioned
      recently. The aim of our study was to evaluate if the extent of a nocturnal BP
      decrease, established on the basis of a single 24-hour BP monitoring, is related
      to cardiovascular remodeling in essential hypertension. We enrolled 253 never
      treated essential hypertensives (24-hour BP > or = 140 and/or 90 mm Hg); for each
      patient we recorded 24-hour BP, left ventricular (LV) echocardiogram, Doppler
      transmitral flow velocities, and carotid-femoral pulse-wave velocities. A dipper
      BP profile was found in 161 patients, whereas 92 patients were nondippers. The 2
      groups did not differ with regard to age, gender, body mass index, 24-hour and
      daytime BP, and 24-hour, daytime, and nighttime heart rate. All LV morphologic
      characteristics LV systolic and diastolic functional parameters, mitral Doppler
      derived diastolic indexes, as well as carotid-femoral pulse-wave velocity, and
      aortic index distensibility were not significantly different between dippers and
      nondippers. The prevalence of LV hypertrophy and diastolic dysfunction was also
      similar between the 2 groups. The extent of a decrease in nocturnal BP did not
      correlate with any cardiovascular parameter. In conclusion, in never-treated
      hypertensives, the extent of a nocturnal BP decrease is not related to LV morpho
      functional characteristics and aortic distensibility; therefore, the nondipping
      status established on the basis of a single 24-hour BP monitoring does not
      identify hypertensive patients with greater cardiovascular damage.

PMID- 12008175
TI  - Effects of perindopril on aldosterone production in the failing human heart.
AB  - The present study was designed to examine whether the production of aldosterone
      from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in
      patients with heart failure. Forty-one patients with left ventricular systolic
      dysfunction were randomly divided into either the perindopril group (n = 21,
      perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone
      and ACE activity were measured in the anterior interventricular vein, coronary
      sinus, and aortic root during cardiac catheterization. The levels of aldosterone
      as well as ACE activity were significantly higher at the anterior
      interventricular vein and the coronary sinus than at the aortic root in the
      placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3
      +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/-
      0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p
      <0.001], respectively). On the other hand, there were no differences in the
      levels of aldosterone or ACE activity between the anterior interventricular vein
      and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1
      +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p =
      NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/
      0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of
      aldosterone as well as ACE activity were significantly lower at the anterior
      interventricular vein and coronary sinus in the perindopril group than in the
      placebo group. The difference in the level of aldosterone between the anterior
      interventricular vein and aortic root (Delta aldosterone [anterior
      interventricular vein - aortic root]) had a significant positive correlation with
      that of ACE activity (Delta ACE [anterior interventricular vein - aortic root])
      (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant
      correlation with either the aldosterone levels in the aortic root or Delta
      aldosterone (anterior interventricular vein - aortic root). Perindopril
      suppressed cardiac aldosterone production by mainly suppressing cardiac ACE
      activity in patients with heart failure. Thus, aldosterone production is
      activated in the failing ventricle and is suppressed by perindopril mainly via
      the suppression of cardiac ACE activity in patients with heart failure.

PMID- 12008176
TI  - Effect of addition of exercise to therapeutic lifestyle changes diet in enabling
      women and men with coronary heart disease to reach Adult Treatment Panel III low
      density lipoprotein cholesterol goal without lowering high-density lipoprotein
      cholesterol.

PMID- 12008177
TI  - Comparison of effect of intensive lipid lowering with atorvastatin to less
      intensive lowering with lovastatin on C-reactive protein in patients with stable
      angina pectoris and inducible myocardial ischemia.

PMID- 12008178
TI  - Incidence of new coronary events in older persons with prior myocardial
      infarction and systemic hypertension treated with beta blockers, angiotensin
      converting enzyme inhibitors, diuretics, calcium antagonists, and alpha blockers.

PMID- 12008179
TI  - Safety of abciximab during percutaneous coronary intervention in patients with
      chronic renal insufficiency.

PMID- 12008180
TI  - False-positive cardiac troponin I in a routine clinical population.

PMID- 12008181
TI  - Comparative three-year performance of chronic atrial sensing among eight
      different VDD systems.

PMID- 12008182
TI  - Usefulness of clinical information to distinguish patients with normal from those
      with low ejection fractions in heart failure.

PMID- 12008183
TI  - Myocardial function in patients with multiple sclerosis treated with low-dose
      mitoxantrone.

PMID- 12008184
TI  - Transcatheter reconstruction using intravascular stents of acquired long-segment
      pulmonary artery discontinuity after the hemi-Fontan procedure associated with
      either congenital mitral stenosis or atresia and hypoplastic left ventricle.

PMID- 12008185
TI  - Magnetic resonance imaging evaluation of cardiac tumor characteristics in infants
      and children.

PMID- 12008186
TI  - Effect of changes in body weight and serum albumin levels on electrocardiographic
      QRS amplitudes.

PMID- 12008187
TI  - Choice of computed tomography, transesophageal echocardiography, magnetic
      resonance imaging, and aortography in acute aortic dissection: International
      Registry of Acute Aortic Dissection (IRAD).

PMID- 12008188
TI  - Impact of gender on rest Tc-99m sestamibi-gated left ventricular ejection
      fraction.

PMID- 12008189
TI  - Hemostasis and exercise.

PMID- 12008190
TI  - Prognostic factors in head and neck cancer.

PMID- 12008191
TI  - The role of ultrasonography as an adjunct to mammography in the detection of
      breast cancer. a systematic review.
AB  - The aim of this review was to summarise the diagnostic performance of
      ultrasonography as an adjunct to mammography in the detection of breast cancer
      and to identify clinical indications. A systematic review was performed of all
      publications in MEDLINE and EMBASE between 1990 and 2000 on the role of
      ultrasonography as an adjunct to mammography. 22 studies were included, showing a
      large variety of indications for ultrasonography and variations in the diagnostic
      performance of mammography and ultrasonography. There were six studies comparing
      a combined diagnosis of mammography and ultrasonography together with mammography
      alone, of which three studies had an increased sensitivity at the cost of a lower
      specificity. The methods of selecting the study population and interpretation of
      ultrasonography significantly influenced the diagnostic performance of
      mammography and ultrasonography relative to each other (P=0.003, P=0.03,
      respectively). Based on the studies reviewed, little evidence-based support was
      found to confirm the well recognised value of ultrasonography as an adjunct to
      mammography in the detection of breast cancer in clinical practice. Furthermore,
      no clinical indications for additional ultrasonography could be defined. The
      heterogeneity in the diagnostic performance in these studies may be explained by
      the methods of patient selection and ultrasonography interpretation, as well as
      by their poor quality.

PMID- 12008192
TI  - Ethical approval for multicentre clinical trials in children. Contrasting systems
      in three European countries.
AB  - Pan-European collaboration in studies of novel therapies and treatment strategies
      in childhood cancer is playing an increasing role in the attempt to improve cure
      rates. Differences in the systems of various countries with regard to drug
      control and ethical issues may lead to problems and delays. This applies in
      particular to phase I/II studies in children where the ethical considerations may
      be complex. In this review, the systems in three large countries-UK, France and
      Germany-are reviewed and current moves within the European Community towards a
      more standard approach are discussed.

PMID- 12008193
TI  - Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx
      with correlations to clinicopathological features.
AB  - The aim of this study was to investigate the prognostic significance of E
      cadherin expression in squamous cell carcinomas of the supraglottic larynx. 101
      primary carcinomas were retrospectively studied. The level of E-cadherin
      expression was determined by immunohistochemistry. There was a significant
      correlation between decreased E-cadherin expression and the presence of nodal
      metastases (P=0.007). T-stage (P=0.025) and histological grade (P=0.043) were
      also associated with nodal metastases. Multivariate analysis confirmed that these
      three parameters were independent predictors of nodal metastases. Decreased E
      cadherin expression also correlated with an increase in recurrence rates
      (P=0.019). However, in multivariate analysis only pathological N-stage was
      significantly associated with disease-specific survival. We conclude that E
      cadherin is an independent predictor of nodal metastases in supraglottic squamous
      cell carcinomas. Determination of E-cadherin expression levels might be useful in
      identifying patients with clinically negative lymph nodes who are at risk of
      occult metastases, allowing more effective treatment strategies to be
      implemented.

PMID- 12008194
TI  - Investigation of the prognostic value of coexpressed erbB family members for the
      survival of colorectal cancer patients after curative surgery.
AB  - Epidermal growth factor receptor (EGFR), erbB2, erbB3 and erbB4 are four
      transmembrane glycoproteins belonging to the subtype I tyrosine kinases. They
      share structure homologies and are believed to direct cellular growth through the
      ligand-stimulated tyrosine phosphorylation of intracellular substrate. The
      overexpression of these tyrosine kinases has been linked to various cancers. To
      examine the role of the erbB family in the neoplastic transformation of the human
      colon, we analysed the protein expression of these four members by
      immunohistochemistry in paraffin-embedded specimens from 125 resected colorectal
      cancers. Our data showed that for EGFR expression, 62 (50%) were scored as '+',
      and 2 (2%) as '++'. For erbB2 expression, 39 (31%) were classified as '+', and 5
      (4%) as '++'. For erbB3 expression, 43 (34%) were scored as '+', and 3 (2%) as
      '++'. A significantly higher percentage of overexpressed erbB3 was observed in
      early stage carcinomas (Dukes' stage A or B) (50%) than in advanced stage cancers
      (Dukes' stage C or D) (15%) (P<0.0001). For erbB4 expression, 22 (18%) were
      scored as '+', and 5 (4%) as '++'. Early stage patients had a lower percentage of
      erbB4 overexpression than the late stage ones (18% versus 28%). Concomitant
      overexpression of erbB2 and erbB3 occurred in 21% (16/78) of the early stage
      carcinomas, whereas it occurred in only 2% (1/47) of the late stage ones
      (P=0.003). Conversely, simultaneous overexpression of erbB2 and erbB4 occurred in
      17% (8/47) of the late stage carcinomas but in only 4% (3/78) of the early stage
      ones (P=0.02). Overexpression of EGFR, erbB2, erbB3 or erbB4 alone was not
      significantly associated with a shortened survival. However, patients with a
      simultaneous overexpression of erbB2 and erbB4 had a shorter overall survival
      time than others in the univariate analysis (P=0.01). This significance
      disappeared after adjustment for Dukes' staging in the Cox model. In conclusion,
      overexpressed erbB3 was common in early stage colorectal cancers, but its
      prevalence was significantly reduced in late stage ones. The percentage of its
      coexpression with erbB2 was significantly higher in early stage than in late
      stage cancers. Heterodimerisation between erbB2 and erbB4 may play a role in the
      late stages of carcinogenesis.

PMID- 12008195
TI  - Phase I and pharmacokinetic study of BIBX 1382 BS, an epidermal growth factor
      receptor (EGFR) inhibitor, given in a continuous daily oral administration.
AB  - The pyrimido-pyrimidine BIBX 1382 BS inhibits the intracellular tyrosine kinase
      domain of the epidermal growth factor receptor (EGFR), thus specifically
      reverting the aberrant enzymatic activity from overexpressed and constitutively
      activated EGFR. A phase I and pharmacokinetic study of this new specific molecule
      was carried out. After initially performing an accelerated titration design from
      the first toxicities onwards, a modified Fibonacci scheme was used to escalate
      the daily oral dose. The following dosages and cycles (defined as treatment
      during 28 days) were applied: 25 mg: 6; 50 mg: 3; 100 mg: 6; 200 mg: 7; 150 mg:
      3. Over a 10 months accrual phase, 11 patients (pts) (7 females, 4 males) with a
      median age of 63 years (range 50-73 years), World Health Organization Performance
      Status (WHO PS) 0:5 pts, 1:6 pts and miscellaneous solid tumours were entered.
      The median number of cycles applied per pt was 2 (range 1-7). Reversible, dose
      dependent increase of liver enzymes (maximal Common Toxicity Criteria (CTC)
      grades: gamma-glutamyl transferase (GGT): 4, aspartate aminotransferase (GOT): 3,
      alanine aminotransferase (GPT): 3, alkaline phosphatase (AP): 3, bilirubin: 3)
      occurred. Oral medication yielded plasma levels far below those expected to be
      efficacious. In conclusion, target plasma levels could not be reached via the
      oral route at a reasonable dosage. Meanwhile, a preclinically unknown metabolite
      was identified from the urine of one patient. Subsequently, this metabolite was
      found to be abundant in patient plasma. The metabolite was demonstrated to be
      pharmacologically inactive. Due to a dose-limiting increase of liver enzymes, low
      bioavailability of BIBX 1382 BS and the detection of a pharmacologically inactive
      metabolite, this trial was discontinued.

PMID- 12008196
TI  - Population pharmacokinetics of adjuvant cyclophosphamide, methotrexate and 5
      fluorouracil (CMF).
AB  - Despite the success of adjuvant cyclophosphamide, methotrexate (MTX), 5
      fluouracil (5-FU) (CMF) treatment for early stage breast cancer, more than 35% of
      patients die within 5 years of diagnosis. Optimisation of the dose of each
      component drug may improve survival and reduce toxicity. In this study, the
      pharmacokinetics of intravenous (i.v.) cyclophosphamide (600 mg/m(2)), MTX (40
      mg/m(2)) and 5-FU (600 mg/m(2)) were determined in 46 women, with data on two
      consecutive courses available for 41 patients. A population analysis using NONMEM
      was performed to investigate the effect of patient covariates on pharmacokinetics
      (PK), and to estimate the relative magnitude of interindividual and interoccasion
      variability. Patient weight had a significant influence on the clearance of
      cyclophosphamide and on the volume of central compartment for MTX, whose
      clearance was dependent on renal function. For all three drugs, interoccasion
      variability was of the same order (20-40%) as that between individuals,
      suggesting a limited potential for dose-optimisation of this regimen.

PMID- 12008198
TI  - Cell kinetic changes in human squamous cell carcinomas during radiotherapy
      studied using the in vivo administration of two halogenated pyrimidines.
AB  - The aim of this study was to investigate cell cycle changes during radiation
      treatment and establish whether treatment intervention could be considered if
      these changes helped to predict outcome. 33 patients with head and neck cancer
      were administered iododeoxyuridine (IdUrd) prior to treatment and a second
      administration of bromodeoxyuridine (BrdUrd) prior to the fifth fraction of 2 Gy.
      Biopsies were taken several hours after each injection and flow cytometry was
      used to calculate changes in the cellular kinetics and cell cycle delay in vivo.
      The kinetic response of the tumour cells was variable; some showed an increase in
      proliferation during the first week of treatment, whilst the majority showed an
      inhibition of proliferation. Reduction in the labelling index (LI) and the
      pretreatment DNA ploidy status and not delays in G2 were the only parameters to
      correlate with clinical outcome. A lack of reduction in the LI after 1 week of
      radiotherapy and DNA aneuploidy predicted a group of patients where radiotherapy
      failed. This information could be helpful in planning future treatment
      interventions.

PMID- 12008197
TI  - Disposition of docetaxel in the presence of P-glycoprotein inhibition by
      intravenous administration of R101933.
AB  - Recently, a study of docetaxel in combination with the new orally administered P
      glycoprotein (P-gp) inhibitor R101933 showed that this combination was feasible.
      However, due to the low oral bioavailability of R101933 and high interpatient
      variability, no further attempts to increase the level of P-gp inhibition were
      made. Here, we assessed the feasibility of combining docetaxel with intravenously
      (i.v.) administered R101933, and determined the disposition of docetaxel with and
      without the P-gp inhibitor. Patients received i.v. R101933 alone at a dose
      escalated from 250 to 500 mg on day 1 (cycle 0), docetaxel 100 mg/m(2) as a 1-h
      infusion on day 8 (cycle 1) and the combination every 3 weeks thereafter (cycle 2
      and further cycles). 12 patients were entered into the study, of whom 9 received
      the combination treatment. Single treatment with i.v. R101933 was associated with
      minimal toxicity consisting of temporary drowsiness and somnolence. Dose-limiting
      toxicity consisting of neutropenic fever was seen in cycles 1 and 2 or in further
      cycles at both dose levels. The plasma pharmacokinetics of docetaxel were not
      changed by the R101933 regimen at any dose level tested, as indicated by plasma
      clearance values of 22.5+/-6.2 l/h/m(2) and 24.2+/-7.4 l/h/m(2) (P=0.38) in
      cycles 1 and 2, respectively. However, the faecal excretion of unchanged
      docetaxel decreased significantly after the combination treatment from 2.5+/-2.1%
      to less than 1% of the administered dose of docetaxel, most likely due to
      inhibition of the intestinal P-gp by R101933. Plasma concentrations of R101933
      were not different in cycles 0 or 2 and the concentrations achieved in the first
      12-h period after i.v. infusion were capable of inhibiting P-gp in an ex vivo
      assay. We conclude that the combination of 100 mg/m(2) i.v. docetaxel and 500 mg
      i.v. R101933 is feasible, lacks pharmacokinetic interaction in plasma, and shows
      evidence of P-gp inhibition both in an ex vivo assay and in vivo as indicated by
      the inhibition of intestinal P-gp.

PMID- 12008199
TI  - Postoperative radiotherapy following mastectomy for high-risk breast cancer. A
      randomised trial.
AB  - Grade III, node-positive breast cancer carries a high risk of loco-regional
      relapse after simple mastectomy. A randomised trial was conducted to assess
      whether this would be significantly reduced by postoperative radiotherapy.
      Between 1985 and 1991, 76 patients who had undergone a simple mastectomy and
      axillary sampling, and whose tumours had been found to be grade III and node
      positive, were randomised to receive postoperative radiotherapy to the chest wall
      and axilla or no further loco-regional treatment. Radiotherapy was delivered with
      8 MV X-rays to the axilla and supraclavicular fossa and with 8 MeV electrons to
      the chest wall, to a dose of 45 Gy in 15 fractions over 3 weeks. All patients
      have been followed-up until death, or for a minimum of 10 years. All loco
      regional recurrences occurred within the first 4 years after mastectomy. There
      were 26 such events in the 40 patients randomised to the 'watch' policy (65%), as
      opposed to 9 out of 36 (25%) who received radiotherapy (P<0.01). Ten-year
      survival was 39% in the radiotherapy arm as opposed to 25% in the no radiotherapy
      arm. Recruitment to the trial was closed in 1991, when a preliminary safety
      analysis revealed the size of the effect of radiotherapy, and from then on all
      node-positive patients with grade III tumours have routinely been given this
      treatment. Further follow-up has confirmed this finding, as borne out by these 10
      year results, which shows that radiotherapy has a significant impact on reducing
      loco-regional recurrence in patients at high risk after mastectomy. There is an
      apparent survival benefit although, because of the small numbers in this trial,
      this has not reached statistical significance.

PMID- 12008200
TI  - Embryonal tumours of the central nervous system.

PMID- 12008201
TI  - Assessing oncological productivity. is one method sufficient?
AB  - This work analyses the distribution of oncological papers published in 1995 by
      authors from the European Union (EU) in any journal of all the Subject Categories
      of the Science Citation Index compiled by ISI (Institute for Scientific
      Information, Philadelphia, USA) and is based on the country of origin of all of
      the contributors. The study compares the results with those of a previous study
      dealing with publications in journals of the ISI Oncology Category based on the
      country of origin of the corresponding author. The aim of the study was to
      compare two different methods used to evaluate research productivity in order to
      understand the extent to which the results are influenced by the methodology
      adopted. Data on the number of published papers for each country, ratio between
      the number of occurrences of papers and country population and gross domestic
      product (GDP), and mean Impact Factors (IF ) were compared. While findings on the
      number of published papers (United Kingdom (UK), Germany and France ranking
      best), source country population (Sweden, Denmark and the Netherlands ranking
      best) and gross domestic product (Sweden, Finland and the Netherlands ranking
      best) showed no important changes, the mean IF value result was, for some
      countries, very different from the previous study. In particular, while Germany,
      Belgium, Portugal and France fared well, Norway, Sweden, Austria and Spain showed
      poorer results. Some hypotheses are advanced, and care in the scientometric
      interpretation of data is urged. An analysis of the journals in which EU authors
      published their articles was also carried out and the main SCI categories to
      which the journals belong are reported. As was expected, many categories other
      than oncology were represented (biochemistry, haematology, pathology, etc.).

PMID- 12008202
TI  - Novel expressed sequences obtained by means of a suppression subtractive
      hybridisation analysis from the 6q21 region that is frequently deleted in gastric
      cancer.
AB  - In our search for genomic regions that are involved in the development of gastric
      cancer, we recently identified a 2-cM minimal region of overlapping heterozygous
      deletions in 6q16.3-q23.1. Here, we describe an application of the suppression
      subtraction method (SSH) to search for genes in this small region of the genome,
      taking advantage of the fact that many human genes present on yeast artificial
      chromosomes (YACs) are expressed in yeast. Subtraction was performed with two
      virtually contiguous YACs that cover a region of approximately 2.5 Mb. Combined
      forward and reversed subtractions resulted in the identification of 12 clones of
      human origin, all of which could be confirmed by sequence analysis as originating
      from the 6q21 region. Expression in human tissues could be confirmed by Northern
      analysis for two of the clones, one of them showing a high level of expression in
      stomach tissue.

PMID- 12008203
TI  - Effects of combination anti-vascular endothelial growth factor receptor and anti
      epidermal growth factor receptor therapies on the growth of gastric cancer in a
      nude mouse model.
AB  - We hypothesised that the combination of anti-angiogenic and anti-epidermal growth
      factor (EFG)-receptor (R) therapies would more effectively inhibit gastric cancer
      growth than single-agent therapy. TMK-1 gastric cancer cells were injected into
      the gastric wall of nude mice to generate tumours. After 4 days, mice were
      randomly assigned to the following groups: control, DC101 ([vascular endothelial
      growth factor (VEGF)-receptor (R)-2 antibody], C225 (EGF-R antibody), or a
      combination of DC101 and C225. The combination therapy significantly inhibited
      gastric tumour growth compared with the control group, whereas the decrease in
      tumour growth in mice treated with DC101 or C225 alone did not reach statistical
      significance. All mice administered DC101 demonstrated decreased tumour
      vascularity and increased endothelial cell apoptosis. C225 alone did not affect
      angiogenesis, but inhibited tumour cell proliferation. The combination therapy
      led to a further decrease in tumour cell proliferation. The combination of anti
      VEGF-R and anti-EGF-R therapies was effective in inhibiting gastric cancer
      growth. These findings support the hypothesis that inhibiting multiple biological
      pathways that mediate tumour growth may be an effective therapeutic strategy.

PMID- 12008204
TI  - Oxaliplatin (L-OHP) treatment of human myeloma cells induces in vitro growth
      inhibition and apoptotic cell death.
AB  - Oxaliplatin (L-OHP), a diaminocyclohexane platinum derivative, is an active and
      well tolerated anticancer drug which is presently used in the treatment of
      gastrointestinal tumours. Since the efficacy of L-OHP in the treatment of
      multiple myeloma (MM) has not yet been evaluated, we studied the
      antiproliferative activity of this compound in vitro in a panel of MM cell lines
      (XG1, XG1a, U266 and IM-9). We found that L-OHP inhibited the growth of MM cells
      at therapeutically achievable concentrations (IC(50): 5-10 microM after 24 h of
      exposure) and was more active than Cisplatin (CDDP) or Carboplatin (CBDCA). The
      activity of L-OHP was apparently not affected by interleukin-6 (IL-6), the major
      growth and survival factor of MM cells. We also found that L-OHP induced
      apoptotic cell death. We demonstrated that the combination of L-OHP with
      Dexamethasone (Dex) resulted in the enhancement of the anti-myeloma effects. L
      OHP and Dex both induced poly adenosine diphosphate (ADP)-ribose polymerase
      (PARP) cleavage and this induction was enhanced by the combined treatment. L-OHP
      induced apoptosis correlated with caspase-3 cleavage, but this correlation could
      not be demonstrated in Dex-treated cells. Taken together, these in vitro results
      provide a rationale for the experimental use of L-OHP in the treatment of MM
      patients and suggest therapeutic combinations of potential value.

PMID- 12008205
TI  - BNP7787, a novel protector against platinum-related toxicities, does not affect
      the efficacy of cisplatin or carboplatin in human tumour xenografts.
AB  - BNP7787 (2',2'-dithio-bis-ethane sulphonate sodium), a water-soluble disulphide,
      is chemically and mechanistically different from other sulphur-containing
      chemoprotective agents. Presently, BNP7787 is under investigation for its
      protective properties with regard to the side-effects of platinum compounds. In
      this study, we evaluated BNP7787, mesna and amifostine for their effects on the
      antitumour activity of platinum compounds. Continuous exposure to BNP7787 did not
      affect the antiproliferative effects of cisplatin or carboplatin, but the
      efficacy of both compounds was reduced in the presence of mesna in vitro in two
      human ovarian cancer cell lines. BNP7787 or amifostine combined with cisplatin or
      carboplatin given in standard schedules for the treatment of nude mice bearing
      well-established OVCAR-3 xenografts did not interfere with platinum-induced
      inhibition of tumour growth. Of interest, BNP7787 or amifostine co-administered
      with carboplatin was significantly more effective than carboplatin alone
      (P<0.01). In the presence of amifostine, doses of cisplatin and carboplatin could
      be safely increased by factors of 1.6 and 1.5, respectively. Unlike in a previous
      study of BNP7787 in tumour-bearing rats, BNP7787 did not protect against
      additional weight loss following treatment with higher doses of cisplatin in
      OVCAR-3-bearing mice. Pharmacokinetics of (mixed) disulphides including BNP7787
      and extractable mesna in deproteinised plasma revealed a rapid disappearance of
      BNP7787 and an AUC(5-60) value of mesna 9-fold lower than that calculated after
      an equivalent dose of mesna by weight. We can conclude that BNP7787 does not
      interfere with the antitumour activity of platinum compounds in vitro and in
      vivo. Clinical trials are underway to evaluate the protection of normal tissues
      by BNP7787 when combined with cisplatin.

PMID- 12008207
TI  - Reporting adverse reactions to medicines.

PMID- 12008208
TI  - Religious aged care homes struggling.

PMID- 12008209
TI  - Coping with body image changes after limb loss.

PMID- 12008210
TI  - Becoming an agent of change.

PMID- 12008211
TI  - Changing public health nursing practice.

PMID- 12008212
TI  - Whither nursing in the 21st century?

PMID- 12008213
TI  - At the heart of nursing.

PMID- 12008214
TI  - Nurses strike action 'unprecedented'.

PMID- 12008215
TI  - Perioperative nurses use humour to release tension.

PMID- 12008223
TI  - Moving towards multi-employer agreements.

PMID- 12008224
TI  - Linking theory with practice.

PMID- 12008225
TI  - Wrestling with Watson's theory of caring.

PMID- 12008226
TI  - Removing barriers to further education.

PMID- 12008228
TI  - Policy reflects change from diploma to degree preparation.

PMID- 12008229
TI  - Double gloving can be a hazard in theatre.

PMID- 12008230
TI  - Clinical career pathways: an overview.

PMID- 12008231
TI  - Developing a national clinical career framework.

PMID- 12008238
TI  - The Nightingale legacy.

PMID- 12008239
TI  - Night respite care: relieving the burden on people caring for relatives with
      dementia.

PMID- 12008240
TI  - Hip fracture prevention in the frail older patient.

PMID- 12008241
TI  - Care for older people with a dementia in acute hospital settings.
AB  - If nurses plan and approach older people with dementia with positive values, and
      learn from the person's communication through their behaviour, the outcomes for
      all parties can be improved. The vignette has offered one example, but also
      demonstrates that there are no failure-proof ways of communicating, and sometimes
      nurses need to learn through trial and error. Only in this way can they become
      more skilled in their interventions to facilitate rather than manage challenging
      behaviours. Avoidance and ignorance do not help in either the short term or the
      long term. The good news is that single interventions are successful 45 per cent
      of the time and multiple interventions, as shown in Box 2, are more successful
      (Bair et al 1999).

PMID- 12008242
TI  - Restraint: its use and misuse in the care of older people.
AB  - Restraint is an emotive issue, with legal and ethical dimensions, as well as
      psychological and physical effects on the person being restrained. Can its use
      ever be justified in the care of older people?

PMID- 12008243
TI  - Assessing age-related sleep disorders.

PMID- 12008244
TI  - The art of caring.

PMID- 12008245
TI  - Free nursing but who pays for education and training?

PMID- 12008246
TI  - Infection control in the care of older adults.

PMID- 12008247
TI  - A matter of trust.

PMID- 12008248
TI  - Framework improves outlook.

PMID- 12008249
TI  - Take me to your leaders.

PMID- 12008250
TI  - HCA regulation. You wanna be in our gang?

PMID- 12008251
TI  - NHS reform. No blame, no pain.

PMID- 12008252
TI  - Clinical requirement.

PMID- 12008253
TI  - Should there be a ban on smoking in public places?

PMID- 12008255
TI  - We should show some faith in the faithless.

PMID- 12008256
TI  - Placement blues.

PMID- 12008257
TI  - No time to die.

PMID- 12008258
TI  - We've got to speculate to innovate.

PMID- 12008259
TI  - Nurse prescribing: a policy overview.
AB  - Nurses play an important role in ensuring that patients receive the maximum
      benefit from any medicines they are prescribed. This includes administering them,
      ensuring that patients understand how to take and store their medication, and
      recognising and acting on any side-effects. Some nurses also prescribe medicines.
      The NHS Plan envisages most nurses being qualified to prescribe or supply
      medicines (under patient group directions) by 2004. This article discusses
      current developments in policy on nurse prescribing and the implications for
      nurses.

PMID- 12008260
TI  - Nursing with dignity. Part 9: Jehovah's Witnesses.
AB  - This article describes the main teachings and customs of Jehovah's Witnesses. It
      offers some guidelines to enable nurses to provide sensitive and appropriate care
      to patients who are Jehovah's Witnesses.

PMID- 12008261
TI  - Why do nurses neglect to report violent incidents?
AB  - Violent incidents have increased in psychiatric hospitals, with 75% of mental
      health nurses and 85% of nurses generally being threatened. Anecdotal evidence
      suggests that inconsistent reporting contributes to poor implementation of
      proactive policies for preventing violent incidents. Using questionnaires to
      generate data, this study tested three hypotheses to determine the factors that
      influence nurses' reporting behaviour. The key finding was that the most likely
      predictor of reporting behaviour is the level of violence and the consequences of
      the incident.

PMID- 12008262
TI  - Do nurses know enough about percutaneous endoscopic gastrostomy?
AB  - An audit of nurses in a district general hospital found that there were gaps in
      their knowledge about the management of percutaneous endoscopic gastrostomy. The
      author suggests ways in which their knowledge could be updated and patient care
      improved.

PMID- 12008263
TI  - Professional development. Medicines. 3. Managing medicines.

PMID- 12008265
TI  - Continence problems following a stroke.

PMID- 12008266
TI  - The role of the occupational therapist in continence care.

PMID- 12008267
TI  - Acute urinary retention: a case study.

PMID- 12008268
TI  - Environmental problems: valuable equipment.

PMID- 12008269
TI  - Continence services in a changing NHS.

PMID- 12008270
TI  - Establishing a user group in continence care.

PMID- 12008271
TI  - Developing continence services through partnership.

PMID- 12008272
TI  - [Undervalued reserves and potential?].

PMID- 12008273
TI  - [Overcoming rehabilitation strategies after a stroke].

PMID- 12008274
TI  - [The difficult patient. Potential conflicts can be speedily recognized].

PMID- 12008275
TI  - [Nursing documentation. Documentation must be learned].

PMID- 12008276
TI  - [Comparison with the industrial life. More professionality is required].

PMID- 12008277
TI  - [Ready to go].

PMID- 12008278
TI  - [A turn that can no longer be tolerated].

PMID- 12008279
TI  - [Information in the patient record. The process is proceeding].

PMID- 12008280
TI  - [Improving nursing records nd the medical establishment. A double challenge to be
      solved].

PMID- 12008281
TI  - [Sexual harassment in the workplace. It is worth the price to defend oneself].

PMID- 12008282
TI  - [A regulation for the hospital. Prevention of passing information].

PMID- 12008283
TI  - [Draining the positive strength].

PMID- 12008284
TI  - [Treating the family in the psychiatric milieu. The need for cooperation].

PMID- 12008285
TI  - [Long term care?--Perhaps later].

PMID- 12008286
TI  - [Vale of pity in practice].

PMID- 12008287
TI  - [The Dutch example. "Problem-based learning" and "skills lab"].

PMID- 12008288
TI  - Detection of ciliostatic activity in fungal growth on building materials.
AB  - Varying ciliostatic activity was found in extracts of biomass from building
      materials inoculated with pure isolates of some molds previously isolated from
      buildings. Extracts from growth on materials composed of finely divided cellulose
      (plaster board and construction cardboard) were more active than those from
      growth on Rockwool. Extracts of biomass from all three materials demonstrated an
      activity greater than control samples. Based on the activity observed here, it is
      conceivable that the measurement of ciliostatic activity of biomass scraped from
      contaminated building materials could be useful for planning removal strategies.

PMID- 12008289
TI  - Photochemical behaviour of the systemic fungicide carboxin.
AB  - Irradiation of carboxin (1) with a 500 W UV lamp (filter Pyrex) in CH3CN leads to
      the products 3, 5-8, 12-14 depending upon the reaction conditions. All photo
      products were isolated and characterized. Photooxidation occurred even if
      unsensitized, while photoalteration was very slow in the absence of oxygen. The
      main oxygenated-products 3 and 13 were also recovered under biomimetic conditions
      by exposure of an aqueous solution of 1 to sunlight.

PMID- 12008290
TI  - Hazard identification and risk assessment procedure for genetically modified
      plants in the field--GMHAZID.
AB  - The safe application of genetically modified organisms (GMOs) requires a risk
      assessment prior to their proposed use. Based on methods from the chemical
      industry, we developed a hazard identification procedure for the risk assessment
      of field tests with genetically modified plants. This risk assessment method,
      GMHAZID, is carried out in the form of guided brainstorm sessions. GMHAZID was
      tested with a case study for which a risk assessment had previously been made,
      and the results of the assessments were compared. The results showed that some
      new hazards potentially leading to uncontrolled spreading, in addition to those
      from the previous assessment, were identified using GMHAZID. GMHAZID also
      recognised some hazards leading to failures in the field experiments. We suggest
      that GMHAZID provides systematics, reliability, and transparency to the risk
      assessment procedure.

PMID- 12008291
TI  - Free-air fumigation of mature trees. A novel system for controlled ozone
      enrichment in grown-up beech and spruce canopies.
AB  - A novel system for continuous and controlled free-air fumigation of mature tree
      canopies with ozone is described. Ozone generated from oxygen is diluted with air
      in a pressurized tank and conducted into the canopies by a system of 100 PTFE
      tubes hanging down from a grid fixed above the crowns. With 45 calibrated outlets
      per tube providing a constant flow of 0.3 l/min each, a total volume of about
      10*10*15 m3 comprising 5 beech and 5 spruce canopies is fumigated. The spatial
      ozone distribution in the fumigated volume as well as surrounding reference tree
      canopies is controlled by continuous measuring instruments installed at 4 levels
      and a dense array of passive samplers. The system will later be used for CO2
      fumigation as well. Results of the first year of continuous operation, with 2 *
      ambient ozone levels having been achieved, are reported.

PMID- 12008292
TI  - Biochemical and molecular studies on declining and decline-resistant spruce in
      the north-east of France.
AB  - In declining forests of the Vosges mountains (northeast of France), we previously
      observed that the yellowing of spruce (Picea abies L. cv. Karsten) needles was
      associated with impairment of the free radical scavenging capacity of the cells
      and coincided with chronic exposure to ozone. Chloroplasts of yellow needles were
      characterized by an abnormal accumulation of photosystem II (PSII) D1-protein in
      the thylakoids. Further experiments carried out on declining and decline
      resistant individual spruce trees characterized in previous studies showed that
      needle yellowing was associated with impairment of the overall anti-oxidative
      defense in both the cytosol and the chloroplasts. Both enzymic (peroxidases) and
      non-enzymic (carotenoids) oxidant scavengers were shown to be affected in the
      declining spruce. PSII D1-protein accumulation seemed to result from a
      stabilization of the polypeptide, which led us to hypothesize that oxidative
      processes might interfere with the specific degradation of this protein in
      declining spruce, with destructive consequences for the photosystems.

PMID- 12008293
TI  - Concentration of LAS and boron in the Itter. Comparison of measured data with
      results obtained by simulation with the GREAT-ER software.
AB  - The GREAT-ER software was used to calculate linear alkylbenzene sulphonate [LAS]
      and boron concentrations in the Itter stream in North Rhine-Westfalia, Germany.
      The aim was to investigate the predictive strength of this newly developed tool
      and to compare its results to measured data. Substance-specific input data which
      were used in this scenario were partly generic (e.g. LAS and sodium perborate
      tetrahydrate consumption figures for Germany) and partly (site-)specific data
      (e.g. half-life time for LAS elimination). The comparison with the measured data
      reveals that the model predictions for LAS and boron are correct at least within
      a factor of two, only if generic German consumption data is applied. By using
      refined input data, the accuracy can be increased further.

PMID- 12008294
TI  - Twenty-five years of biomonitoring lead in the Frankfurt/Main area.
AB  - The present study is an example of the historical monitoring of heavy metals. The
      specific question it aims to explore is: to what extent has the lead content of
      selected organisms used for biomonitoring in Frankfurt/Main--one of the cities in
      Germany most heavily affected by automobile traffic--changed as a result of
      legislation on leaded gasoline? Data on the lead content of the moss species
      Bryum argenteum Hedw. from the years 1974, 1975 and 1978 and data on the lead
      content of the outer bark of the ash species Fraxinus excelsior L. from 1973
      served as the basis for the repeated measurements. Remeasurement was successful
      in 76.5% (i.e. 124 trees at 26 growth sites). The study produced the following
      results: As was expected, the lead content of the short-term accumulator Bryum
      argenteum Hedw. was distinctly lowered with a decreasing particulate lead
      concentration. However, the reduction factor varied greatly between the different
      growth sites. On the other hand, the lead content measured in the outer bark
      layers of Fraxinus excelsior L. has risen markedly during the past two decades.
      Whereas in 1973 nearly all trees examined displayed very low concentrations of
      lead (< 38 ppm), only 9.5% were still in this category in 1997 and nearly 30%
      exhibited high or even unacceptable lead concentrations (< 150 ppm-->225 ppm).
      Various factors have to be taken into account to explain this increase. First of
      all, bark is a long-term accumulator for heavy metals like lead and its
      enrichment capacity could have increased as the surface becomes rougher over
      time. Furthermore, lead is most probably leached out of the bark to a lesser
      degree now than in the 1970s, owing to the reduced concentration of sulphuric
      acid in the rain. The dramatic growth of automobile traffic in the Frankfurt/Main
      area during the period covered by the study undoubtedly plays an important role
      as well.

PMID- 12008295
TI  - Application of rare-earth elements in the agriculture of China and its
      environmental behavior in soil.
AB  - Rare-earth elements (REEs) have been used in fertilizers in the agriculture of
      China for about 20 years. They have been shown to be beneficial elements for
      plants. For example, they have improved the yield and quality for several kinds
      of crops. This paper reviews the current literature on studies of REEs being used
      as fertilizers. Some studies have focused on the effects of REEs on metabolic
      nutrients, photosynthesis and stress resistance of plants. Other studies have
      shown that the environmental behaviors of REEs in soil are dominated by their low
      solubility. Fluorides, carbonates, phosphates and hydroxides may form neutral
      complexes containing REEs with a low solubility. The amount of extraneous REEs
      demonstrate the following relationship: residual >> bound to organic matter >
      bound to Fe-Mn oxides > bound to carbonate >> exchangeable and water soluble
      forms. The adsorption capacity of REEs depends on the clay type and the content
      of amorphous and manganese oxides, whereas the desorption of REEs is usually very
      low. At the end of the paper, authors discuss the needs for future environmental
      research on REEs, which would shed new light on the effects of REEs on
      agriculture, environment and human health.

PMID- 12008296
TI  - Environmental chemistry education in Europe: setting the agenda. 1st Workshop
      organised by the Committee on Education in Environmental Chemistry (CEEC) of FECS
      -Division of Chemistry and the Environment (DCE) in Rome, Italy, January 10-12,
      2002.

PMID- 12008297
TI  - Report on the Second International Conference on 'Naturally Produced
      Organohalogens' (Heidelberg, Germany, September 30 to October 3, 2001).

PMID- 12008298
TI  - International Summit on Science and the Precautionary Principle. Lowell Center
      for Sustainable Production, University of Massachusetts Lowell, USA September 20
      22, 2001.

PMID- 12008299
TI  - Biosafety in the international context--the Cartagena protocol.

PMID- 12008300
TI  - Climate change problems and carbon dioxide emissions: expecting 'Rio + 10'.
      Global Summit on Sustainable Development in Johannesburg (26th August-6th
      September 2002).

PMID- 12008302
TI  - Domestic violence training guidelines to be launched.

PMID- 12008301
TI  - Renewable energies for climate benign fuel production. Powering fuel-cell
      vehicles.

PMID- 12008303
TI  - Combating nurse resistance to 'flu vaccines.

PMID- 12008304
TI  - Proposal aims to streamline patient complaints' systems.

PMID- 12008305
TI  - Nurses need better protection from injuries.

PMID- 12008306
TI  - Resolution to strengthen nursing and midwifery.

PMID- 12008307
TI  - Raising awareness of family violence.

PMID- 12008308
TI  - Acting to combat violence.

PMID- 12008309
TI  - Emergency nurses facing more violence.

PMID- 12008310
TI  - Nurses' role in protecting children.

PMID- 12008311
TI  - Nurses must take a stand against violence.

PMID- 12008312
TI  - Nursing council policy change denigrates nurses.

PMID- 12008313
TI  - Organisational psychopaths and our health culture.

PMID- 12008314
TI  - Case study: how radical ward changes caused the loss of nursing skills.

PMID- 12008315
TI  - Ramsden's arguments failed to convince.

PMID- 12008316
TI  - Preparing an exemplar for assessment.

PMID- 12008317
TI  - No more silence on violence.

PMID- 12008318
TI  - Ensuring parties bargain in good faith.

PMID- 12008319
TI  - Students meet heads of nursing schools.

PMID- 12008320
TI  - Advancing nursing through research.

PMID- 12008321
TI  - Projecting sensitivity and openness.

PMID- 12008322
TI  - Nelson nurse struggles to enlarge practice.

PMID- 12008323
TI  - Taking care in our use of language.

PMID- 12008325
TI  - Better communication among students needed.

PMID- 12008324
TI  - Student article insults Taranaki Polytechnic.

PMID- 12008326
TI  - Post-graduate education benefits everyday practice.

PMID- 12008327
TI  - [Setting down quality in the present].

PMID- 12008328
TI  - [Definitive contra-indications for menopausal hormone replacement therapy].

PMID- 12008329
TI  - [Patient education in a self surveillance and self control].

PMID- 12008330
TI  - [Professional practice. Multidisciplinary care for infections of the diabetic
      foot].

PMID- 12008331
TI  - [Professional practice. Record of care: for whom, why?].

PMID- 12008332
TI  - [Words from Europe. Complaints from Polish patients in the face of promises and
      outcome].

PMID- 12008333
TI  - [The accreditation visit in practice].

PMID- 12008334
TI  - [Organization. Self-evaluation, for advancing together].

PMID- 12008335
TI  - [Organization. Preparation for the accreditation visit from the Committee on
      Accreditation of Angers].

PMID- 12008336
TI  - [An inspection from accreditation in psychiatry].

PMID- 12008337
TI  - [Organization. An implication on distribution].

PMID- 12008338
TI  - [Appreciation by patients for a new method of insulin administration: 3 ml.
      Humapen].

PMID- 12008340
TI  - Cultivating cultural harmony.

PMID- 12008339
TI  - [The Internet as pedagogic tool in nursing care].

PMID- 12008341
TI  - Giving a voice to health consumers.

PMID- 12008342
TI  - Developing a cultural safety curriculum.

PMID- 12008343
TI  - Developing safe nursing practice for Maori.

PMID- 12008344
TI  - Integrating cultural safety into practice.

PMID- 12008345
TI  - Service sees decrease in readmission rates.

PMID- 12008346
TI  - Nurses must be aware of their power.

PMID- 12008347
TI  - Creating a safe workplace.

PMID- 12008348
TI  - Improving practice through research.

PMID- 12008349
TI  - Setting standards for nurses and services.

PMID- 12008350
TI  - Cultural safety values difference.

PMID- 12008359
TI  - Champion for older people.

PMID- 12008360
TI  - The power of song.

PMID- 12008361
TI  - Communication and dementia.

PMID- 12008362
TI  - Education and person-centred approaches to dementia care.

PMID- 12008363
TI  - Older people with dementia in acute settings.
AB  - This article suggests that screening and assessing for dementia can be
      incorporated into nurses' roles, as can a range of strategies to address some of
      the common challenges that nurses face when working with older people with
      cognitive impairment in acute settings.

PMID- 12008364
TI  - Assessing gastrointestinal (GI) tract functioning in older people.

PMID- 12008365
TI  - Nursing homes--crisis of escalating closures.

PMID- 12008366
TI  - No secrets in nursing homes.

PMID- 12008367
TI  - Student experiences in nursing homes. A response.

PMID- 12008368
TI  - Student experiences in nursing homes: a placement policy gap.

PMID- 12008369
TI  - Promoting wellbeing in older people with cognitive impairment.

PMID- 12008370
TI  - Care home closedown.

PMID- 12008371
TI  - Time to die?

PMID- 12008372
TI  - Community-based NHS nursing homes for older people with mental illness.

PMID- 12008373
TI  - Assessing older people--contemporary issues for nursing.

PMID- 12008374
TI  - Influenza vaccination.
AB  - Nurses have an important part to play in dispelling myths about influenza
      vaccination and in actively encouraging older people to attend for vaccination.
      Irene Schofield discusses the issues.

PMID- 12008375
TI  - Assessing endocrine system function in older people.

PMID- 12008376
TI  - Tackling ageism--a new year resolution.

PMID- 12008377
TI  - Improving falls management.

PMID- 12008378
TI  - Winter of discontent.

PMID- 12008379
TI  - Student experiences in nursing homes: a placement policy gap?

PMID- 12008380
TI  - Applying sound principles of medication use for older people.

PMID- 12008381
TI  - Playing the numbers game.

PMID- 12008382
TI  - Health care assistants.

PMID- 12008383
TI  - The forgotten generation.

PMID- 12008384
TI  - Student experiences in nursing homes: a placement policy gap?

PMID- 12008385
TI  - Promoting mobility and physical functioning in older people.

PMID- 12008386
TI  - Living environments and older people.
AB  - The influence of care environments on patients has long been a fundamental
      concern for nurses. Considerations of how environments might be defined,
      particularly how multiple aspects of environments might impact on any individual,
      are complex. This article aims to unpick some of the complexities and to offer
      ideas on how nurses can positively influence environments, particularly in
      settings where older people live and are offered care.

PMID- 12008387
TI  - Assessing pulmonary function in older people.

PMID- 12008388
TI  - Falling into the chasm.

PMID- 12008389
TI  - Bullying.

PMID- 12008390
TI  - Winter of discontent.

PMID- 12008391
TI  - When is nursing care personal?

PMID- 12008392
TI  - Powerful whispers.

PMID- 12008393
TI  - Oral health in long-term care settings.

PMID- 12008394
TI  - Implementing an oral hygiene assessment tool on an acute medical ward for older
      people.

PMID- 12008395
TI  - Oral health in older people.
AB  - Oral health is an area which is often overlooked when caring for older people.
      This article gives guidelines on how to ensure that older people do not suffer
      discomfort and diseases in the mouth.

PMID- 12008397
TI  - Human rights--not best interests.

PMID- 12008396
TI  - Assessing orthostatic hypotension in older people.

PMID- 12008398
TI  - Defining nursing and personal care.

PMID- 12008399
TI  - Changing care homes. Changing practice.

PMID- 12008400
TI  - Bringing down the Berlin Wall.

PMID- 12008401
TI  - Hearing older voices in Wales.

PMID- 12008402
TI  - Tai Chi for older people.

PMID- 12008403
TI  - Preventing pressure ulcers: the work of the residential homes nursing team.

PMID- 12008404
TI  - Supporting older people with acute confusion: the contribution of mental health
      nurses.

PMID- 12008405
TI  - The care of older people with a delirium in acute care settings.
AB  - This article suggests that nurses should play a major part in the screening,
      assessment and management of delirium in older people in acute settings.

PMID- 12008406
TI  - Assessing the gastrointestinal (GI) tract in older people: 2. The lower GI tract.

PMID- 12008407
TI  - The dilemmas of putting a price on care.

PMID- 12008408
TI  - Hands off the nurse manager.

PMID- 12008409
TI  - Laughter still the best medicine.

PMID- 12008410
TI  - Education and person-centred approaches to dementia care.

PMID- 12008411
TI  - Sexually transmitted infections and older people.

PMID- 12008412
TI  - Funding nursing and personal care.

PMID- 12008413
TI  - Three cheers for Scotland.

PMID- 12008414
TI  - Charging ahead.

PMID- 12008415
TI  - Hidden talents: bringing out the dark horse.

PMID- 12008416
TI  - Transdermal patch use and older people.

PMID- 12008417
TI  - Long-term analgesics and older people--a hidden addiction?

PMID- 12008418
TI  - Medications and older people.
AB  - The key to benefiting older people through medication lies in the proper
      diagnosis of illness, correct prescription of drugs and vigilant monitoring of
      intended and unintended drug actions.

PMID- 12008419
TI  - Assessing cardiovascular functioning in older people.
AB  - The cardiovascular system comprises the heart and blood vessels. The heart
      circulates the blood through the vascular system to supply oxygen and nutrients
      to the peripheral tissues and remove carbon dioxide and other waste products. The
      blood has other functions such as distributing heat around the body and fighting
      infection. With the cardiovascular system it is difficult to separate the effects
      of normal ageing from disease processes (Watson 2000a). However, the process of
      atherosclerosis is almost universal in older people and is largely responsible
      for the higher prevalence of cardiovascular problems in older people (Hall et al
      1993).

PMID- 12008420
TI  - New plan--new look journal.

PMID- 12008421
TI  - The new Data Protection Act.

PMID- 12008422
TI  - Long-term issues.

PMID- 12008423
TI  - National care standards.

PMID- 12008424
TI  - [Scab wounds 2001].

PMID- 12008425
TI  - [Refractory wounds and a therapeutic impasse].

PMID- 12008426
TI  - [Scars and nutrition].

PMID- 12008427
TI  - [What's new in burns and scabs?].

PMID- 12008428
TI  - [Supports to aid in prevention and care].

PMID- 12008429
TI  - [How does one ask about wounds and scars?].

PMID- 12008430
TI  - [Evidence based medicine and the treatment of wounds].

PMID- 12008431
TI  - [Foot ulcers].

PMID- 12008432
TI  - [Care without encroachment].

PMID- 12008433
TI  - [Quality and universality for nursing in urology].

PMID- 12008434
TI  - [4,000 supplementary jobs in the five years since the advent of home
      hospitalization].

PMID- 12008435
TI  - [The number of nurse victims of workplace violence].

PMID- 12008436
TI  - [Reducing urinary handicaps].

PMID- 12008438
TI  - [Education of the diabetic patient, a growing necessity].

PMID- 12008437
TI  - [Pain affected by scarring].

PMID- 12008439
TI  - [Roferon--a simplified interferon].

PMID- 12008440
TI  - [Professional practice. ABCD...for the use of the patient].

PMID- 12008441
TI  - [Patients in the first world war. The saving reinforcement of the benevolent
      hospital attendant].

PMID- 12008442
TI  - [Public health. Can one prevent suicide?].

PMID- 12008443
TI  - [Intimacy across Europe].

PMID- 12008444
TI  - [Local nursing. Agreement of the network of geriatric services of the Mutual
      Agricultural Society].

PMID- 12008445
TI  - [Privacy and nurse patient relations].

PMID- 12008446
TI  - [Nursing strategies. Accepting privacy in nursing care].

PMID- 12008447
TI  - [Testimony. Privacy without intimacy].

PMID- 12008448
TI  - [Nursing strategies. The proper distance].

PMID- 12008449
TI  - [Alcoholism in a colleague].

PMID- 12008450
TI  - [Nursing strategies. The nurse in the presence of sexuality of the aged].

PMID- 12008452
TI  - [Psychology. The nurse and the violence of intimacy].

PMID- 12008451
TI  - [Al Warith, the searcher for souls and the magic baton].

PMID- 12008454
TI  - [Paris, health promotion world capital].

PMID- 12008455
TI  - [Eight major measures for students].

PMID- 12008456
TI  - [The French Transplantation Organization appeals for more organ donation].

PMID- 12008461
TI  - [The nursing profession in Europe, the first evaluation].

PMID- 12008462
TI  - [Professional practice. Restraint and non-restraint, measuring the potential
      risks (3/3)].

PMID- 12008463
TI  - [Evaluating and managing fatigue in oncology].

PMID- 12008464
TI  - [Public health. Urinary incontinence in France].

PMID- 12008465
TI  - [Reparative surgery for stress urinary incontinence in women].

PMID- 12008466
TI  - [Nursing strategy. Incontinence, an intimate handicap].

PMID- 12008467
TI  - [Nursing strategy. Management of incontinence in elderly institutionalized
      persons].

PMID- 12008468
TI  - [Independent practice. Prevention and management of incontinence at home].

PMID- 12008469
TI  - [Incontinence: symptom, disease or taboo?].

PMID- 12008470
TI  - [6/12. Drugs and hepatic insufficiency].

PMID- 12008471
TI  - [Pain and patient controlled analgesia].

PMID- 12008472
TI  - [Management of an overdose].

PMID- 12008473
TI  - [Nursing care and preventive actions. 4/6--prevention of urinary incontinence].

PMID- 12008474
TI  - [Hospitals search for nurses ... desperately!].

PMID- 12008475
TI  - A sharper focus. Part 1.

PMID- 12008476
TI  - Reviewing nursing and residential home placements in Cheshire.

PMID- 12008477
TI  - Streptococcal infection and older people.

PMID- 12008478
TI  - Promoting healthy skin in older people.
AB  - As people age, natural changes occur in the skin that put older people at risk of
      poor or compromised skin health.

PMID- 12008479
TI  - Principles of pain assessment in older people--Part 1.

PMID- 12008480
TI  - Older people's specialist.

PMID- 12008481
TI  - The nurse consultant.

PMID- 12008482
TI  - Care for dying people in nursing homes.

PMID- 12008483
TI  - 'Confusion' greets free nursing care.

PMID- 12008484
TI  - Getting involved.

PMID- 12008485
TI  - Fighting off 'flu.

PMID- 12008487
TI  - ["Nursing is above all an act of love and fraternity" Interview by Bernadette
      Fabregas].

PMID- 12008490
TI  - [Professional practice. ABCDaire ... applied to nursing practice].

PMID- 12008491
TI  - [Nurses during the first World War. The necessary passage from volunteerism to
      professionalism].

PMID- 12008492
TI  - [Biotechnology applications in health].

PMID- 12008493
TI  - [Genetic therapy and clinical challenges].

PMID- 12008494
TI  - [Genetic research and nursing role].

PMID- 12008495
TI  - [Cellular and genetic therapy applications at the Nantes University Hospital
      Center].

PMID- 12008496
TI  - [Gene therapy, bioethics and rights].

PMID- 12008497
TI  - [Biotechnologies should not build cathedrals of health technology].

PMID- 12008498
TI  - [3/12. Drugs and renal and hepatic transplant patients].

PMID- 12008499
TI  - [Triennial plan in pain prevention].

PMID- 12008500
TI  - [Care and prevention actions. 1/6. Prevention of decubitus ulcers].

PMID- 12008501
TI  - ["Which decree for what nursing practice?" Part 2].

PMID- 12008502
TI  - Nurses may hold key to finding father.

PMID- 12008503
TI  - NZNO's professional colleges and sections at work.

PMID- 12008504
TI  - District health boards promise service integration.

PMID- 12008505
TI  - Measuring nurses' workloads.

PMID- 12008506
TI  - Enhancing NZNO's professional strength.

PMID- 12008507
TI  - How exemplars are assessed.

PMID- 12008508
TI  - Exemplar: reversing respiratory depression.

PMID- 12008509
TI  - Researching post-tonsillectomy bleeding.

PMID- 12008510
TI  - Linking research with clinical practice.

PMID- 12008511
TI  - What can we learn from Gisborne?

PMID- 12008512
TI  - Rediscovering the essence of cancer nursing.

PMID- 12008513
TI  - District nurses to play vital role in primary health strategy.

PMID- 12008514
TI  - Nursing's cultural safety model is a source of pride.

PMID- 12008515
TI  - Psychiatric nurses' role is not to cope with violence.

PMID- 12008516
TI  - Cultural safety issue fails to include other races.

PMID- 12008517
TI  - English nurse chooses to ignore racist insults.

PMID- 12008518
TI  - Nursing council policy change challenged.

PMID- 12008519
TI  - Nursing Council policy aims for greater flexibility.

PMID- 12008520
TI  - Clinical career pathways can lead to discrimination.

PMID- 12008521
TI  - Double gloving should be mandatory in theatre.

PMID- 12008522
TI  - Enrolled nurse training back at last.

PMID- 12008524
TI  - [Towards better care of the diabetic patient].

PMID- 12008527
TI  - [News in the management of chronic neuropathic diabetic ulcer].

PMID- 12008528
TI  - [Forming palliative care teams. Interview by Bernadette Fabregas].

PMID- 12008529
TI  - [Professional practice. Restraint and non-restraint, measuring the potential
      risks (1/3)].

PMID- 12008530
TI  - [Patient education. Diabetes and urinary self monitoring].

PMID- 12008531
TI  - [Pain, a public health priority?].

PMID- 12008532
TI  - [Pain representations by nurses].

PMID- 12008533
TI  - [Taking care of chronic pain, or the relationship with others].

PMID- 12008534
TI  - [Pain evaluation scale or the myth of the magic ruler].

PMID- 12008535
TI  - [Nursing care. When words fail....].

PMID- 12008536
TI  - [Nursing care. Pain in adult intensive care, a fatality?].

PMID- 12008537
TI  - [The nurse's role in management of a migraine patient].

PMID- 12008538
TI  - [What role for nurses in managing pain?].

PMID- 12008539
TI  - [4/12. Drugs and renal insufficiency].

PMID- 12008540
TI  - [Management of acute pain in children].

PMID- 12008541
TI  - [Management in cases of caustic product ingestion].

PMID- 12008542
TI  - [Bernard Kouchner wants to install "a pedagogy of health risk" Interview by
      Ghislaine Trabacchi].

PMID- 12008543
TI  - ["The XXI th century will be one of health in the world." Interview by Celine
      Dekussche].

PMID- 12008545
TI  - [Pedagogy. Education, a pleasure at work].

PMID- 12008546
TI  - Benign or malign? Media stereotyping.

PMID- 12008547
TI  - Developing a stroke education programme.

PMID- 12008548
TI  - Possible effects of unrealistic expectations of recovery after stroke.

PMID- 12008549
TI  - Renal disease in older people.
AB  - There has been a significant rise in the incidence of renal failure in older
      people. This article gives an overview of possible causes and treatment.

PMID- 12008550
TI  - Assessing dietary intake in older people.

PMID- 12008551
TI  - Nursing or personal care--who decides?

PMID- 12008552
TI  - National service framework. A GNP response.

PMID- 12008553
TI  - Closing time.

PMID- 12008554
TI  - Oral health in older people.

PMID- 12008555
TI  - Changes for good and bad.

PMID- 12008556
TI  - Another brick in the wall.

PMID- 12008557
TI  - Dementia and art.

PMID- 12008558
TI  - Oral assessment and intervention.

PMID- 12008559
TI  - The Easy-Care assessment system and its appropriateness for older people.

PMID- 12008560
TI  - Side rails as physical restraints: the need for appropriate assessment.
AB  - Side rails are commonly used in the care of the older person. They can be
      classified as a physical restraint if they restrict the movement of an individual
      and also if the individual has an inability to have them removed/lowered at will.
      Advanced age should not be an indicator for side rail use and an individualized
      approach in patient assessment is advised.

PMID- 12008561
TI  - Assessment of older people using medication.

PMID- 12008562
TI  - Good ideas--poor experiences.

PMID- 12008563
TI  - A shared experience.

PMID- 12008564
TI  - Living environments and older people.

PMID- 12008565
TI  - Ethical recruitment of nurses from overseas to the independent sector.

PMID- 12008566
TI  - Shifting the balance.

PMID- 12008567
TI  - Life after a stroke.

PMID- 12008568
TI  - Student placements in nursing homes.

PMID- 12008569
TI  - Infection control in older people.

PMID- 12008570
TI  - Care for dying people in nursing homes.
AB  - Nurses who are confident in their own skills but who know where to draw upon
      specialist help can provide enormous support for nursing home residents coming to
      the end of their lives. Promoting a palliative care approach can promote a sense
      of well-being in older people who are dying.

PMID- 12008571
TI  - Assessing renal function in older people.

PMID- 12008572
TI  - Tough decisions ahead.

PMID- 12008573
TI  - Why we need dementia care nursing.

PMID- 12008574
TI  - Applying sound principles of nutrition in nursing homes.

PMID- 12008575
TI  - Government launches new care standards for nursing homes.

PMID- 12008576
TI  - Eight years on.

PMID- 12008577
TI  - Going the extra mile.

PMID- 12008578
TI  - [A taboo disease?].

PMID- 12008579
TI  - [Evaluating the quality of the sections of implantable catheters].

PMID- 12008580
TI  - [Professional practice. ABCD...a practice for the nurse].

PMID- 12008581
TI  - [Public health. What happens after a suicide crisis?].

PMID- 12008582
TI  - [Patient education. In the presence of a hypoglycemic coma].

PMID- 12008583
TI  - [Nursing strategies. Multiple sclerosis, medical and therapeutic strategies].

PMID- 12008584
TI  - [Nursing strategies. Urinary and sexual problems in patients with multiple
      sclerosis].

PMID- 12008585
TI  - [Nursing strategies. A clinic dedicated to multiple sclerosis].

PMID- 12008586
TI  - [Professional practice. Multiple sclerosis and home care].

PMID- 12008587
TI  - [Professional practice. Psychological support for patients with multiple
      sclerosis and their families].

PMID- 12008588
TI  - [Pain and manipulation of the patient].

PMID- 12008589
TI  - [Behavior in the presence of the sudden death of an infant].

PMID- 12008590
TI  - [Continuing care, help and comfort. 6/6--care of patients with AIDS].

PMID- 12008593
TI  - [Compliance and type II diabetes, can we do better?].

PMID- 12008596
TI  - [Nurses during the First World War. A modern vision of nursing care and the
      recognition of sacrifices].

PMID- 12008597
TI  - [Professional practice. Restraint and non-restraint, measuring the potential
      risks (2/3)].

PMID- 12008598
TI  - [AIDS in Romania, a critical situation].

PMID- 12008599
TI  - [AIDS prevention, results and strategies].

PMID- 12008600
TI  - [AIDS treatment and daily life].

PMID- 12008601
TI  - [AIDS, which therapeutic management today?].

PMID- 12008602
TI  - [A nursing consultation for helping therapeutic compliance].

PMID- 12008603
TI  - [AIDS, social reformer].

PMID- 12008604
TI  - [Prevention of AIDS in high school students].

PMID- 12008605
TI  - [AIDS in Senegal, a public health world challenge].

PMID- 12008606
TI  - [All, rather than amnesia].

PMID- 12008607
TI  - [5/12. Drugs and the dialysis patient].

PMID- 12008608
TI  - [Drugs and pain].

PMID- 12008609
TI  - [Management of the patient who has fallen out of a window].

PMID- 12008610
TI  - [Nursing care and prevention actions. 3/6. Prevention of constipation].

PMID- 12008611
TI  - ["It's time to put a real public health policy in place." Interview by Celine
      Dekussche].

PMID- 12008612
TI  - [Nurses in oncology, from specialization to specialty].

PMID- 12008613
TI  - Listen to us.

PMID- 12008614
TI  - Clinical effectiveness and clinical teams: effective practice with older people.

PMID- 12008615
TI  - Empowerment, disempowerment and the care of older people.

PMID- 12008616
TI  - Working with older people from minority ethnic groups.
AB  - Living in a multi-cultural community means nurses in all specialties must have an
      understanding of the diverse ethnic backgrounds of their patients. This applies
      equally to nurses working with older people, who can enhance the care they give
      by facilitating adequate, appropriate and accessible services for all patients,
      irrespective of ethnic origin.

PMID- 12008617
TI  - Assessing the musculoskeletal system in older people.

PMID- 12008618
TI  - Thanks for the election memory.

PMID- 12008619
TI  - Collaboration in action.

PMID- 12008620
TI  - Caring for older people with a delirium.

PMID- 12008621
TI  - Who cares wins.

PMID- 12008622
TI  - An uncertain future.

PMID- 12008623
TI  - Art works.

PMID- 12008624
TI  - Developing a community stroke rehabilitation service.

PMID- 12008625
TI  - Infection control in older people.

PMID- 12008626
TI  - Rehabilitation in nursing homes.
AB  - Rehabilitation is a key concept in the government's plans to modernize the NHS.
      Its aim is to restore a person's autonomy, although there are sometimes barriers
      to making effective rehabilitation a reality, some of which are explored here,
      along with ways of helping teams in nursing homes to undertake more effective
      rehabilitation.

PMID- 12008627
TI  - Sexuality and older people: an introduction to nursing assessment.

PMID- 12008628
TI  - Drugs for dementia.

PMID- 12008629
TI  - End of 'a good innings' and the start of something better?

PMID- 12008630
TI  - Campaigners demand that the new government fights to end age discrimination.

PMID- 12008631
TI  - Sexuality and older women.

PMID- 12008632
TI  - A special case.

PMID- 12008633
TI  - A sharper focus.

PMID- 12008634
TI  - Healthcare research agendas for older people: an international comparison.

PMID- 12008635
TI  - Handling the pressure.

PMID- 12008636
TI  - Continence: an update on policy priorities and practice implications in primary
      care.
AB  - Recent national policies have created new frameworks and guidance on the
      assessment and treatment of continence problems. This article offers an update on
      new policy initiatives relevant to nurses working with older people and discusses
      the implications for primary care.

PMID- 12008637
TI  - Principles of pain assessment in older people--Part 2.

PMID- 12008638
TI  - Building bridges.

PMID- 12008639
TI  - Skin care.

PMID- 12008640
TI  - Assessment of older people using medication.

PMID- 12008641
TI  - Medications and older people.

PMID- 12008642
TI  - Progress limited on 'free' nursing care.

PMID- 12008643
TI  - Funded care: sorting fact from fiction.

PMID- 12008644
TI  - Kaleidoscope of excellence. An interview with Lawrence Scahill, PhD, RN.

PMID- 12008645
TI  - Maternal carbohydrate intake and pregnancy outcome.
AB  - Experimental evidence indicates that the primary maternal environmental factor
      that regulates feto-placental growth is substrate delivery to the placental site,
      which is the product of maternal substrate levels and the rate of placental-bed
      blood flow. Thus, maternal factors which change either substrate level or flow
      alter feto-placental growth rate. The best-studied substrate in human pregnancy
      is glucose, and there is a direct relationship between maternal blood glucose
      levels and size at birth. Altering the type of carbohydrate eaten (high- v. low
      glycaemic sources) changes postprandial glucose and insulin responses in both
      pregnant and non-pregnant women, and a consistent change in the type of
      carbohydrate eaten during pregnancy influences both the rate of feto-placental
      growth and maternal weight gain. Eating primarily high-glycaemic carbohydrate
      results in feto-placental overgrowth and excessive maternal weight gain, while
      intake of low-glycaemic carbohydrate produces infants with birth weights between
      the 25th and the 50th percentile and normal maternal weight gain. The calculated
      difference in energy retention with similar total energy intakes is of the order
      of 80,000 kJ. Preliminary information from subsequent metabolic studies indicates
      that the mechanisms involved include changes in: daily digestible energy
      requirements (i.e. metabolic efficiency), substrate utilization (glucose
      oxidation v. lipid oxidation), and insulin resistance and sensitivity. Thus,
      altering the source of maternal dietary carbohydrate may prove to be a valuable
      tool in the management of pregnancies at risk for anomalous feto-placental growth
      and for the prevention and/or treatment of obesity and insulin resistance in the
      non-pregnant state.

PMID- 12008646
TI  - [Euthanasia. Open discussion in the context of pain therapy and palliative
      medicine is also necessary in Germany].

PMID- 12008647
TI  - Can we "switch" the emphasis please?

PMID- 12008648
TI  - Nocturnal lower body positive pressure to counteract microgravity-induced cardiac
      remodeling/atrophy.

PMID- 12008650
TI  - Scientific ethics.

PMID- 12008649
TI  - Exercise, extravascular lung water, and gas exchange.

PMID- 12008651
TI  - On-road facility to measure and characterize emissions from heavy-duty diesel
      vehicles.
AB  - In response to lingering concerns about the utility of dynamometer data for
      mobile source emissions modeling, the U.S. Environmental Protection Agency (EPA)
      has constructed an on-road test facility to characterize the real-world emissions
      of heavy-duty trucks. The facility was designed to effectively demonstrate the
      full range of vehicle operation and to measure the emissions produced. Since it
      began operation, the facility has been continuously upgraded to incorporate state
      of-the-art technology. Its potential uses include collecting modal emissions
      data, validating dynamometer test parameters and results, and demonstrating new
      emission control technologies.

PMID- 12008652
TI  - The relationship between cepstral peak prominence and selected parameters of
      dysphonia.
AB  - Traditional measures of dysphonia vary in their reliability and in their
      correlations with perceptions of grade. Measurements of cepstral peak prominence
      (CPP) have been shown to correlate well with perceptions of breathiness. Because
      it is a measure of periodicity, CPP should also predict roughness. The ability of
      CPP and other acoustic measures to predict overall dysphonia and the
      subcategories of breathiness and roughness in pathological voice samples is
      explored. Preoperative and postoperative speech samples from 19 patients with
      unilateral recurrent laryngeal nerve paralysis who underwent operative
      intervention were analyzed by trained listeners and by measures of smoothed CPP
      (CPPS), noise-to-harmonic ratio (NHR), amplitude perturbation quotient (APQ),
      relative average perturbation (RAP), and smoothed pitch perturbation quotient
      (sPPQ). The data were analyzed with bivariate Pearson correlation statistics.
      Grade of dysphonia and breathiness ratings correlated better with measurements of
      CPPS than with the other measures. CPPS from samples of connected speech (CPPS-s)
      best predicted overall dysphonia. None of the measures were useful in predicting
      roughness.

PMID- 12008653
TI  - Laryngeal chondroma.
AB  - Cartilaginous tumors of the larynx represent less than 1% of laryngeal tumors.
      Chondroma and "low-grade" chondrosarcoma are the most common; 70%-75% of these
      tumors arise on the endolaryngeal surface of the posterior lamina of the cricoid
      cartilage. The clinical presentation is varied and directly dependent on the size
      and location of the tumor; stridor, hoarseness, dyspnea, or a neck mass are
      common presenting signs. CT scanning in the axial plane is the mainstay of
      radiographic imaging due to its ability to show size, extent of the tumor, and
      invasion into surrounding structures. Surgical extirpation is the standard
      therapy with no role for radiation therapy or chemotherapy. Although significant
      recurrence rates have been reported, there is not a significant difference
      between initial conservative therapy followed by salvage therapy versus initial
      radical therapy.

PMID- 12008654
TI  - Comparison of moments and couple-generating forces near discontinuities in
      structural-acoustic systems.
AB  - In modeling vibration isolators in structural-acoustic systems, the isolator's
      dynamic properties are often treated as acting only in the axial direction as
      moments are often neglected. Furthermore, the size, or scale, of the isolator is
      often neglected and the isolator is assumed to act at single points on the
      connected structures. Previous work has shown that concentrated moments can be
      particularly important when located near a fixed support or a structural
      discontinuity. This research extends that work to examine the importance of
      moment scale effects for a system containing a distributed structural
      discontinuity with its own scale. Moment scale effects are examined by
      determining the difference in radiated acoustic power for a simple system that is
      excited by a couple-generating distributed force and a concentrated moment. The
      distributed force produces a couple that is equivalent to the concentrated
      moment. As a result, only the scale is being examined. Particular interest occurs
      when the excitation is located near the structural discontinuity. Based on the
      cases studied here, moment scale is shown to be important at lower frequencies
      when the excitation is located near the edges of the discontinuity. At higher
      frequencies, any overlap of the excitation and discontinuity may warrant the need
      to consider moment scales.

PMID- 12008655
TI  - Monoclonal antibody therapy with autologous peripheral blood stem cell
      transplantation for non-Hodgkin's lymphoma.
AB  - BACKGROUND: With the introduction of novel monoclonal antibody products into the
      clinic, significant new strategies are being developed to improve upon existing
      treatment for non-Hodgkin's lymphoma. METHODS: Monoclonal antibodies are being
      used alone, in combination with chemotherapy, or as adjuncts to autologous bone
      marrow transplantation for the purpose of purging bone marrow of neoplastic
      cells. RESULTS: Monoclonal antibodies when used in vivo in conjunction with
      autologous bone marrow transplantation have been relatively well tolerated.
      Results from several trials seem to demonstrate a therapeutic benefit for the use
      of such combinations. CONCLUSIONS: Before these agents can be included in
      standard bone marrow transplantation regimen, long-term survival outcomes need to
      be obtained from randomized trials. We review the results from recent trials
      using monoclonal antibodies in conjunction with autologous stem cell
      transplantation for the treatment of non-Hodgkin's lymphoma.

PMID- 12008656
TI  - Anxiety sensitivity as a specific and unique marker of anxious symptoms in youth
      psychiatric inpatients.
AB  - We addressed several questions regarding the relation of anxiety sensitivity to
      anxious symptoms among 47 youth psychiatric inpatients (18 boys, 29 girls), ages
      9-17 (M = 14.23, SD = 1.89). Participants completed measures of anxiety
      sensitivity, anxious and depressive symptoms, trait anxiety, and positive and
      negative affect; chart diagnoses were available. Consistent with hypotheses, we
      found that (a) anxiety sensitivity was associated with anxious symptoms, even
      controlling for trait anxiety and depressive symptoms; and (b) anxiety
      sensitivity displayed symptom specificity to anxious versus depressive symptoms
      (i.e., was associated with anxiety controlling for depression but not with
      depression controlling for anxiety). Furthermore, regarding factors of anxiety
      sensitivity, we obtained mixed support for our prediction that phrenophobia would
      be associated with both depression and anxiety, whereas fear of physical arousal
      would be associated with anxiety but not depression. Implications for the
      construct validity of anxiety sensitivity were discussed.

PMID- 12008657
TI  - Young adult outcome of children with "situational" hyperactivity: a prospective,
      controlled follow-up study.
AB  - To examine the importance of symptom pervasiveness in ADHD, we conducted a
      prospective, 12-year follow-up study of boys (ages 6-12) considered hyperactive
      at school and home (Pervasive ADHD), boys considered hyperactive by teachers but
      not parents (School Only ADHD), boys considered hyperactive by parents but not
      teachers (Home Only ADHD), and nonhyperactive comparisons. Follow-up was
      completed on 82-94% participants. Clinicians interviewed participants and their
      parents, blind to childhood status. At follow-up, antisocial disorder was
      significantly more prevalent among Pervasive and School Only ADHD (29% for both)
      than Home Only ADHD (0%) and comparisons (8%). In a similar manner, severity of
      behavioral problems distinguished groups (Pervasive, School > Home, comparisons),
      as did educational attainment and academic performance (poorest for Pervasive and
      School). These findings stress the validity of teacher reports in the diagnosis
      of ADHD.

PMID- 12008658
TI  - Sliders.

PMID- 12008659
TI  - A brief screening tool for suicidal symptoms in adolescents and young adults in
      general health settings: reliability and validity data from the Australian
      National General Practice Youth Suicide Prevention Project.
AB  - Using data from a nationwide project on young people in Australia aimed at
      assessing suicidality in general health settings, we present a brief screening
      tool for suicidality (the depressive symptom index suicidality subscale). Two
      thousand eight hundred and fifty-one (15-24 year old) patients presenting to 247
      Australian general practitioners between 1996 and 1998 were assessed. In addition
      to the suicide screen, patients completed the general health questionnaire-12 and
      the Center for Epidemiological Studies depression scale. Patients' chief
      complaints were taken from the summary sheets completed by their general
      practitioners. Using inter-item correlational and factor-analytic techniques, as
      well as a general approach to construct validity, we show that the measure has
      favorable reliability and validity characteristics. We also provide results on
      cut-points that may facilitate its use in clinical and research settings. Because
      the screen is brief, easy to use, reliable, and valid, we encourage its use to
      combat the vexing international health problem of suicide.

PMID- 12008660
TI  - Relationship of fertility to ovarian follicular waves before breeding in dairy
      cows.
AB  - Cows with two waves of follicular growth during the estrous cycle yield follicles
      that are older and larger at ovulation compared with cows having three waves. The
      objectives of the current research were 1) to compare fertility in cows with two
      or three follicular waves and 2) to examine associations between luteal function,
      follicular development, and fertility after breeding. Follicular waves were
      monitored by ultrasonography during the estrous cycle before insemination in 106
      dairy cows. Fewer cows had three follicular waves before next estrus and
      ovulation than two waves (P < 0.01; 30% vs 68%, respectively), but pregnancy rate
      was higher (P = 0.058; 81 vs 63%, respectively). Cows with two waves had shorter
      estrous cycles (P < 0.01), with the ovulatory follicle being both larger (P <
      0.05) and older (P < 0.01). In cows with three waves, luteal function was
      extended (P < 0.05) and the peak in plasma progesterone occurred later (P < 0.05)
      in the estrous cycle compared to two wave cows. Considering cows that became
      pregnant, luteal phase length was shorter (P < 0.05) during the estrous cycle
      preceding insemination than for nonpregnant cows. In conclusion, fertility was
      greater in lactating cows inseminated after ovulation of the third-wave follicle
      that had developed for fewer days of the estrous cycle as compared with two-wave
      cows.

PMID- 12008661
TI  - Growth performance of stocker calves backgrounded on sod-seeded winter annuals or
      hay and grain.
AB  - Economically viable options for retaining ownership of spring-born calves through
      a winter backgrounding program are somewhat limited in the southeastern United
      States. Although sod-seeded winter annual forages produce less forage than those
      same forages planted using conventional tillage practices, sod-seeded winter
      annual forages have the potential to provide a low-cost, rapid-gain, ecologically
      and economically viable option for retaining ownership of fall-weaned calves. A
      study was conducted during the winters of 1998, 1999, and 2000 using 180
      crossbred calves (261 +/- 2.8 kg initial BW; n = 60 each year) to compare sod
      seeded winter annual forages with conventional hay and supplement backgrounding
      programs in southeast Arkansas. Calves were provided bermudagrass hay (ad
      libitum) and a grain sorghum-based supplement (2.7 kg/d) on 1-ha dormant
      bermudagrass pastures or were grazed on 2-ha pastures of bermudagrass/dallisgrass
      overseeded with 1) annual ryegrass, 2) wheat plus annual ryegrass, or 3) rye plus
      annual ryegrass at a set stocking rate of 2.5 calves/ha. Calves grazed from mid
      December until mid-April but were fed bermudagrass hay during times of low forage
      mass. Mean CP and IVDMD concentrations were 19.0 and 71.1%, respectively, across
      sampling dates and winter annual forages, but three-way interactions among forage
      treatments, year, and sampling date were detected (P < 0.01) for forage mass,
      concentrations of CP, and IVDMD. The IVDMD of rye plus ryegrass was greater (P <
      0.05) than that of ryegrass in yr 2. A forage treatment x sampling date
      interaction was detected for forage CP in yr 1 (P < 0.05) and 2 (P = 0.05) but
      not in yr 3 (P = 0.40). Forage mass did not differ (P > or = 0.22) among winter
      annual treatments on any sampling date. During the first 2 yr, calves fed hay
      plus supplement gained less (P < 0.05) BW than calves that grazed winter annual
      forages; gains did not differ (P > or = 0.23) among winter annual treatments.
      During the 3rd yr, undesirable environmental conditions limited growth of the
      winter annual forages; total gain did not differ (P = 0.66) among the four
      treatments. Winter annual forages offer potential to provide high-quality forage
      for calves retained until spring, but consistent forage production and quality
      are a concern when sod-seeding techniques are used.

PMID- 12008662
TI  - Estimated genetic parameters for carcass traits of Brahman cattle.
AB  - Heritabilities and genetic and phenotypic correlations were estimated from
      feedlot and carcass data collected from Brahman calves (n = 504) in central
      Florida from 1996 to 2000. Data were analyzed using animal models in MTDFREML.
      Models included contemporary group (n = 44; groups of calves of the same sex, fed
      in the same pen, slaughtered on the same day) as a fixed effect and calf age in
      days at slaughter as a continuous variable. Estimated feedlot trait
      heritabilities were 0.64, 0.67, 0.47, and 0.26 for ADG, hip height at slaughter,
      slaughter weight, and shrink. The USDA yield grade estimated heritability was
      0.71; heritabilities for component traits of yield grade, including hot carcass
      weight, adjusted 12th rib backfat thickness, loin muscle area, and percentage
      kidney, pelvic, and heart fat were 0.55, 0.63, 0.44, and 0.46, respectively.
      Heritability estimates for dressing percentage, marbling score, USDA quality
      grade, cutability, retail yield, and carcass hump height were 0.77, 0.44, 0.47,
      0.71, 0.5, and 0.54, respectively. Estimated genetic correlations of adjusted
      12th rib backfat thickness with ADG, slaughter weight, marbling score, percentage
      kidney, pelvic, and heart fat, and yield grade (0.49, 0.46, 0.56, 0.63, and 0.93,
      respectively) were generally larger than most literature estimates. Estimated
      genetic correlations of marbling score with ADG, percentage shrink, loin muscle
      area, percentage kidney, pelvic, and heart fat, USDA yield grade, cutability,
      retail yield, and carcass hump height were 0.28, 0.49, 0.44, 0.27, 0.45, -0.43,
      0.27, and 0.43, respectively. Results indicate that sufficient genetic variation
      exists within the Brahman breed for design and implementation of effective
      selection programs for important carcass quality and yield traits.

PMID- 12008663
TI  - [Retraction. Temporary placement of inferior vena cava filter prior to
      transcatheter arterial embolization (TAE) for hepatocellular carcinoma with IVC
      tumor thrombus--prevention of pulmonary tumor emboli after TAE].

PMID- 12008664
TI  - Phase I study of JM-216 (an oral platinum analogue) in combination with
      paclitaxel in patients with advanced malignancies.
AB  - This phase I study was conducted to determine the dose limiting toxicity, maximum
      tolerated doses, and recommended phase II doses of the combination of JM-216 and
      paclitaxel. Patients received paclitaxel intravenously over one hour on day 1 of
      each cycle. Oral JM-216 was administered on days 1-5 starting after the
      paclitaxel infusion. Cycles were repeated every 21 days. Patients were accrued at
      nine different dosing combinations. JM-216 doses ranged from 10-80 mg/m2/day and
      were combined with paclitaxel doses of 150, 175, or 200 mg/m2. Forty-three
      patients were treated with 146 cycles of therapy. Dose-limiting toxicity,
      consisting of febrile neutropenia and grade 3 thrombocytopenia, was encountered
      in 2 patients at the seventh dose level (JM-216 80 mg/m2/day + paclitaxel 175
      mg/m2). Two intermediate dose levels were explored. The first level (JM-216 70
      mg/m2/day + paclitaxel 175 mg/m2) produced dose-limiting thrombocytopenia in 1 of
      6 patients. However, two additional patients also demonstrated delayed recovery
      from thrombocytopenia following treatment. As a result, a second intermediate
      dose level (JM-216 60 mg/m2/day + paclitaxel 200 mg/m2) was filled with six
      patients. No dose-limiting toxicities were reported in any patients at this dose
      level. The combination of oral JM-216 and paclitaxel is well-tolerated with
      minimal non-hematologic and reversible hematologic toxicity. The recommended dose
      for phase II study is JM-216 60 mg/m2/day for 5 days and paclitaxel 200 mg/m2 on
      day 1 repeated every 21 days. Higher doses of JM-216 are associated with more
      severe thrombocytopenia and delayed hematologic recovery resulting in subsequent
      dosing delays.

PMID- 12008665
TI  - Job mobility, its determinants, and its effects: longitudinal data from the
      Maastricht Cohort Study.
AB  - This prospective study of 12,140 employees examined the effects of work
      characteristics and situational, psychological, and health aspects on job
      mobility. Before job change, the mobility group reported significantly more
      conflicts with the supervisor, higher physical and emotional strain, higher
      degree of job insecurity, lower job satisfaction, and lower degree of commitment
      compared with employees who did not change jobs. After job change, the mobility
      group reported improved autonomy, task diversity, decreased occurrence of
      conflicts with the supervisor, decreased physical and emotional strain, and
      improved training possibilities and job security than before the change. Changing
      jobs had a positive effect on employees with respect to job perception and job
      satisfaction and led to reduced fatigue and need for recovery.

PMID- 12008666
TI  - Project meeting report: International Workshop on Cardiovascular Disease and
      Diabetes among Indigenous Peoples in the Circumpolar North, August 31--September
      1, 2000 Nuuk, Greenland.

PMID- 12008667
TI  - Family history and colorectal cancer screening: a survey of physician knowledge
      and practice patterns.
AB  - OBJECTIVES: Risk stratification is essential to effective implementation of
      colorectal cancer (CRC) screening strategies. The objectives of this study were
      to assess and compare the current knowledge and practice patterns of
      gastroenterologists and primary care physicians regarding familial risk of CRC.
      METHODS: We conducted a survey of regional gastroenterologists and a sample of
      university- and community-based primary care physicians. The survey instrument
      assessed physician knowledge of screening recommendations and current practices
      for individuals with family histories of CRC, adenomatous polyps (APs), familial
      adenomatous polyposis (FAP), and hereditary nonpolyposis cancer (HNPCC). The
      instrument also elicited data about familial risk assessment, documentation, and
      notification of at-risk family members. RESULTS: Thirty-five gastroenterologists
      (65%) and 58 primary care physicians (92%) completed the survey. Most
      gastroenterologists and primary care physicians (85% vs 72%) chose age 40 as the
      appropriate age to begin screening for a family history of CRC, but relatively
      few (37% vs 36%) recommended screening at age 40 for a family history of APs.
      Gastroenterologists were significantly more likely to recommend screening for FAP
      at puberty (80% vs 27%, p < 0.001) and for HNPCC at age 25 (73% vs 50%, p =
      0.04). Colonoscopy was the preferred screening strategy by both groups for family
      histories of CRC (97%), HNPCC (97%), and APs (77%); primary care physicians also
      preferred colonoscopy for family histories of CRC (72%) and HNPCC (76%) but
      flexible sigmoidoscopy plus fecal occult blood testing for a family history of
      APs (38%). Gastroenterologists were more likely to recommend genetic testing for
      persons at risk of FAP (91% vs 71%, p = 0.03) and HNPCC (72% vs 57%, p = 0.18),
      routinely inquire about a family history of CRC or APs (93% vs 63%, p < 0.001),
      and recommend notification of at-risk first-degree relatives with family
      histories of CRC (94% vs 55%, p < 0.001) or AP (53% v.s 6%, p < 0.001).
      CONCLUSION: Although gastroenterologists are more likely than primary care
      physicians to elicit a family history of colorectal neoplasia and implement
      appropriate screening strategies, overall compliance with recommended guidelines
      and notification of at-risk relatives are suboptimal. Novel approaches for
      improving awareness of the available screening guidelines are needed.

PMID- 12008668
TI  - Safety of selective cyclooxygenase-2 inhibitors in inflammatory bowel disease.
AB  - OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are relatively
      contraindicated in patients with inflammatory bowel disease (IBD) for fear of
      disease aggravation. Cyclooxygenase-2 inhibitors have fewer GI side effects than
      traditional NSAIDs in unselected patients. We report the safety of these agents
      in patients with IBD. METHODS: Patients with Crohn's disease, ulcerative colitis,
      or pouchitis who used celecoxib or rofecoxib were identified from computerized
      prescription records. A retrospective chart review was conducted. Concomitant
      medications, past NSAID use, indication for cyclooxygenase-2 inhibitor, dose, and
      duration were obtained. IBD disease activity before cyclooxygenase-2 inhibitor
      use was graded using a modified disease activity index. Change in disease
      activity was graded as improved, no change, or worsened. Patients were contacted
      to provide data not found in the charts. The proportion of patients receiving
      cyclooxygenase-2 inhibitors who experienced exacerbation of IBD was determined.
      RESULTS: Eleven patients were treated with celecoxib (median dose = 200 mg/day),
      and 16 patients were treated with rofecoxib (median dose = 25 mg/day). Median
      duration of therapy was 9 months (range = 1 wk-22 months). The drug was
      beneficial in 14 patients, of partial benefit in eight, and of no benefit in
      five. Two patients (7.4%) (95% CI = 2-23%) had aggravations of IBD. Three
      patients (11%) had other adverse events (renal insufficiency, rash, and
      asymptomatic colonic ulceration). All adverse events were reversible.
      CONCLUSIONS: Our preliminary results suggest that cyclooxygenase-2 inhibitors may
      be safe and beneficial in most patients with IBD. A placebo-controlled trial to
      confirm these preliminary observations is needed.

PMID- 12008669
TI  - The fate of low grade dysplasia in ulcerative colitis.
AB  - OBJECTIVE: The optimal strategy for the management of definite low grade
      dysplasia (LGD) detected in surveillance in ulcerative colitis (UC) is unknown,
      because the natural history of LGD has not been well described. METHODS: We
      reviewed the Mayo Clinic records of patients with UC found to have flat LGD
      between 1990 and 1993 in whom a nonoperative strategy was pursued for 2 months or
      more. RESULTS: Eighteen patients with UC and LGD were observed for a median of 32
      months. Nine of 18 patients identified with UC and LGD developed advanced
      neoplastic lesions during follow-up, which were defined as adenocarcinoma, raised
      dysplasia, or high grade dysplasia. The cumulative incidence of progression to an
      advanced lesion was 33% at 5 yr (95% CI = 9-56%). Only one patient developed
      adenocarcinoma, diagnosed 74 months after his initial finding of LGD and 20
      months after his last surveillance exam. Besides this patient, adenocarcinoma was
      not detected in the colectomy specimens of 13 other patients who underwent
      surgery. Colectomies were performed for dysplasia or cancer in seven patients,
      active colitis in five patients, and unknown reasons in two patients. Four
      patients did not have colectomies. CONCLUSIONS: Neoplastic progression in
      patients with UC and LGD is common. Total proctocolectomy should be offered to
      all patients with flat LGD. Our study illustrates numerous pitfalls in the
      practice of surveillance.

PMID- 12008670
TI  - [Phototherapy and photosensitizing agents].

PMID- 12008671
TI  - [New therapeutic prospects with capecitabin in breast carcinoma].

PMID- 12008672
TI  - [Could the patient suffering be palliated with less painful treatments?].

PMID- 12008674
TI  - Visual-spatial neglect in a child following sub-cortical tumor resection.
AB  - Although clinical syndromes of visual-spatial neglect have been well described in
      adults, clinical features of neglect associated with subcortical dysfunction are
      infrequently reported in children and have not been described in detail.
      Unilateral visual-spatial neglect in a 7-year-old male following removal of a
      right subcortical juvenile pilocytic astrocytoma is reported. Preoperative
      baseline neurocognitive assessment of the patient established intact attentional
      and intellectual functioning. Postoperatively visual-spatial neglect was observed
      that was not accounted for by the patient's visual field deficit. Consistent with
      classic features of attentional neglect, increases in attentional demands led to
      greater errors in performance. The risk of unilateral neglect following resection
      of subcortical tumors that abut the thalamus or disrupt thalamo-cortical
      projections was confirmed in a retrospective analysis of patients referred for
      neurocognitive testing at our site. It was concluded that the ventral thalamus
      may play a role in visual-spatial attention early in development.

PMID- 12008673
TI  - Development and characterization of a reconstituted yeast translation initiation
      system.
AB  - To provide a bridge between in vivo and in vitro studies of eukaryotic
      translation initiation, we have developed a reconstituted translation initiation
      system using components from the yeast Saccharomyces cerevisiae. We have purified
      a minimal set of initiation factors (elFs) that, together with yeast 80S
      ribosomes, GTP, and initiator methionyl-tRNA, are sufficient to assemble active
      initiation complexes on a minimal mRNA template. The kinetics of various steps in
      the pathway of initiation complex assembly and the formation of the first peptide
      bond in vitro have been explored. The formation of active initiation complexes in
      this system is dependent on ribosomes, mRNA, Met-tRNAi, GTP hydrolysis, elF1,
      elF1A, elF2, elF5, and elF5B. Our data indicate that elF1 and elF1A both
      facilitate the binding of the elF2 x GTP x Met-tRNAi complex to the 40S ribosomal
      subunit to form the 43S complex. elF5 stimulates a step after 43S complex
      formation, consistent with its proposed role in activating GTP hydrolysis by elF2
      upon initiation codon recognition. The presence of elF5B is required for the
      joining of the 40S and 60S subunits to form the 80S initiation complex. The step
      at which each of these factors acts in this reconstituted system is in agreement
      with previous data from in vivo studies and work using reconstituted mammalian
      systems, indicating that the system recapitulates fundamental events in
      translation initiation in eukaryotic cells. This system should allow us to couple
      powerful yeast genetic and molecular biological experiments with in vitro kinetic
      and biophysical experiments, yielding a better understanding of the molecular
      mechanics of this central, complex process.

PMID- 12008675
TI  - Appendiceal mucinous tumor.

PMID- 12008676
TI  - Barraging the biliary tree.

PMID- 12008677
TI  - Will the safest analgesic please stand up.

PMID- 12008678
TI  - One if by gut and two if iv.

PMID- 12008679
TI  - Sympathetic hyperactivity in pre-ascites.

PMID- 12008680
TI  - Endothelial dysfunction in children with type 1 diabetes mellitus.
AB  - Endothelial dysfunction is defined as the loss of endothelium properties, e.g.
      alteration of protein synthesis, increased vascular tone and permeability,
      acquisition of prothrombotic and antifibrinolytic properties. Endothelium, a
      primary target of unbalanced glycaemic control, is involved in the pathogenesis
      of vascular complications in patients with type 1 diabetes mellitus (DM).
      Vascular endothelium damage is characterised by an increase of endothelium
      derived regulatory proteins. vWF and t-PA may be useful to investigate early
      endothelium involvement. However, impaired endothelium-dependent vasodilatation
      may be a more sensitive marker. Abnormal markers of endothelial cell activation
      and impaired endothelium-dependent vasodilatation have been observed in young
      patients with type I DM. Hyperglycaemia may alter normal endothelium functions,
      either directly or indirectly, by inducing different metabolic pathways. Complete
      understanding of the pathophysiology of endothelial dysfunction may lead to
      timely therapeutic intervention to prevent its development and to slow the
      progression of diabetic complications.

PMID- 12008681
TI  - Transition of the adolescent from the children's to the adults' diabetes clinic.
AB  - The transition of adolescents with type 1 diabetes mellitus (T1DM) from pediatric
      to adult diabetological care is a critical phase that requires special attention.
      A considerable proportion of adolescents encounters certain difficulties during
      this transition, which can negatively affect adjustment and glycemic control.
      Etiological factors include: (a) the adolescent's separation anxiety elicited by
      the process of departing from the pediatrician who functions as a secure base in
      a period of developmental turmoil; (b) certain developmental factors that
      adversely affect glycemic control and the patient-physician cooperation; (c) the
      tendency of the adult diabetologist to focus more on medical than on psychosocial
      components; (d) the lack of the appropriate preparatory work which would: (i)
      help the adolescent to successfully cope with the difficulties that may arise due
      to the transition and (ii) make feasible the establishment of the proper
      pediatrician-adult diabetologist cooperation required for the development of a
      continuum in diabetological care through which the adolescent's special needs can
      be best met. Practical propositions about certain basic problem-solving
      components concerning the transition from the pediatric to adult diabetes clinic
      are briefly discussed.

PMID- 12008682
TI  - Comparative trial between insulin glargine and NPH insulin in children and
      adolescents with type 1 diabetes mellitus.
AB  - The objective of this study was to compare the efficacy and safety of insulin
      glargine, a long-acting insulin analog, with NPH insulin in children and
      adolescents with type 1 diabetes mellitus (T1DM). In a multicenter, open-label,
      randomized, 6-month study, 349 patients with TIDM, aged 5-16 years, received
      insulin glargine once daily or NPH insulin either once or twice daily, based on
      their prior treatment regimen. Although there was no significant difference
      between the NPH insulin and insulin glargine treatment groups with respect to
      baseline to endpoint change in HbA1c levels, fasting blood glucose (FBG) levels
      decreased significantly more in the insulin glargine group (-1.29 mmol/l) than in
      the NPH insulin group (-0.68 mmol/L, p = 0.02). The percentage of symptomatic
      hypoglycemic events was similar between groups; however, fewer patients in the
      insulin glargine group reported severe hypoglycemia (23% vs 29%) and severe
      nocturnal hypoglycemia (13% vs 18%), although these differences were not
      statistically significant (p = 0.22 and p = 0.19, respectively). Fewer serious
      adverse events occurred in the insulin glargine group than in the NPH insulin
      group (p < 0.02). A once-daily subcutaneous dose of insulin glargine provides
      effective glycemic control and is well tolerated in children and adolescents with
      T1DM.

PMID- 12008683
TI  - TSH secretory pattern and thyroid function in children with growth hormone
      neurosecretory dysfunction.
AB  - We evaluated the TSH secretory pattern and free T4 in 10 prepubertal children
      with short stature, normal response to GH provocative tests, and reduced GH
      integrated concentration (IC-GH) (GH neurosecretory dysfunction). Although their
      nadir TSH, peak TSH, TSH surge, and free T4 were lower than those of 12 children
      with short stature and normal IC-GH, none of the differences reached statistical
      significance. Thus, our results suggest that children with low IC-GH (GH
      neurosecretory dysfunction) exhibit a TSH secretory pattern and thyroid function
      similar to those with normal IC-GH.

PMID- 12008684
TI  - Longitudinal study of the pubertal growth spurt in children born small for
      gestational age without postnatal catch-up growth.
AB  - Most children born small for gestational age (SGA) experience extensive catch-up
      growth during the first months of life (87%) and by the age of 2 years only 13%
      are below -2 SDS for height. The long-term outcome, including pubertal growth
      spurt, of the subset of children born SGA without postnatal catch-up (SGAWPC) has
      been evaluated in very few surveys, and in none of them was the landmarks of
      puberty well described. Thus, a longitudinal study was conducted in these
      children throughout puberty since this is the only reliable way to accurately
      evaluate the pubertal growth spurt. In an observational, retrospective and
      multicenter collaborative study, from an initial group of 553 SGA children, a
      subset of 15 boys (BW = 2,070 +/- 379.6 g) and 16 girls (BW = 2,244 +/- 331.1 g)
      SGAWPC whose data were recorded regularly during puberty were selected. Growth
      standards for growth and maturity during puberty were Tanner and Whitehouse and
      Spanish Hernandez and Sobradillo charts. In pubertal growth spurt, 'take-off'
      occurred later than in the reference populations with a height SDS deficiency of 
      2.3 and -2.2 for boys and -2.0 and -1.9 for girls, compared with Spanish and
      Tanner references, respectively. Peak height velocity was normal in chronology
      and intensity, but the total pubertal gain was smaller. However, considering
      their growth from the same chronological age at which the reference populations
      took off until adulthood, the total gain was not significantly different in the
      three cohorts (32.5 +/- 5.4 cm vs 30.9 +/- 4.4 in boys, and 23.3 +/- 4.1 vs 25.7
      +/- 5.4 cm in girls - Spanish reference - and 27.2 +/- 6.3 vs 27.6 +/- 3.5 cm in
      boys - Tanner charts), except in the case of girls (21.1 +/- 3.9 vs 25.3 +/- 4.1
      cm, p <0.005 - Tanner charts). Adult height was significantly reduced (161.9 +/-
      3.9 cm in males and 147.0 +/- 2.6 cm in females). Therefore, although the
      pubertal growth was smaller in these children, puberty probably did not modify
      their short final height.

PMID- 12008685
TI  - Anti-HBs response to standard hepatitis B vaccination in children and adolescents
      with diabetes mellitus.
AB  - Patients with type 1 diabetes mellitus are expected to respond poorly to
      hepatitis B (HB) vaccination. In this study we tested this hypothesis for the
      standard vaccination schedule. Ninety-nine patients (age 10.8 +/- 3.5 years) were
      vaccinated against HB (10 pg/dose at 0, 1, and 6 months) using a vaccine
      containing no pre-S2 antigen (Engerix Bs). The sero-conversion and -protection
      rates after the completion of three doses, the relation of anti-HBs titers to
      clinical parameters, and comparison with those of healthy counterparts (51
      children, aged 9.7 +/- 4.4 years) were analyzed. The vaccine used was pre-S2
      antigen containing (Genhevac B) in 23 and Engerix B in 28; both types yielded a
      similar response. The geometric mean of the anti-HBs titer was 322.9 vs 1476.8
      IU/l (non-significant), sero-convertion rate 96.9% vs 100%, and seroprotection
      rate 93.9% vs 99% in the diabetic and control groups, respectively. In the
      diabetic group, there was no correlation between anti-HBs titer and clinical
      characteristics except for age. We concluded that the standard vaccination
      schedule is less effective but still effective enough in children and adolescents
      with type 1 diabetes mellitus.

PMID- 12008686
TI  - Epidemiology of 21-hydroxylase deficiency in Singapore.
AB  - We report the incidence and epidemiology of 21-hydroxylase deficiency in
      Singapore, based on a retrospective study of all known patients diagnosed with
      classical 21-hydroxylase deficiency in the past 21 years. The database was
      obtained from the case registry and questionnaire methodology, with 100% coverage
      of all practising pediatricians in Singapore. There were 42 patients affected
      with 21-hydroxylase deficiency in 964,558 live births over 21 years, comprising
      64.3% salt wasters and 35.7% simple virilizers, of whom 50.0% were males and
      50.0% females. The incidence of classical 21-hydroxylase deficiency is 4.5 per
      100,000 live births, with a carrier frequency of 1:76, and a gene frequency of
      0.0067. Although retrospective studies have inherent limitations, the gender and
      phenotype ratios suggest that the data provide a crude incidence level. This
      study underscores the necessity for prospective neonatal screening, so that the
      benefits of early diagnosis and treatment can be realized.

PMID- 12008687
TI  - Stiffness of the abdominal aorta in obese children.
AB  - Obesity is pathogenically related to clinical and subclinical disorders that
      contribute to the development of atherosclerotic plaques and their complications
      leading to onset of cardiovascular events. Arterial stiffness may be an indicator
      of early vascular changes signaling the development of vascular disease. The
      purpose of this study was to assess the stiffness of the abdominal aorta using
      transthoracic echocardiography in normotensive obese and hypertensive obese
      pediatric patients and a control group. The study group consisted of 25 healthy
      children (M/F: 13/12) as a control group (Group I), 25 normotensive obese
      children (M/F: 13/12) (Group II) and 25 hypertensive obese children (M/F: 14/11)
      (Group III). The mean ages were 12.1 +/- 1.8, 11.9 +/- 1.5 and 12.4 +/- 1.4
      years, respectively. Aortic strain (S), pressure strain elastic modulus (Ep) and
      normalized Ep (Ep*) measurements were significantly different in the hypertensive
      obese group, and cholesterol levels and body mass index were higher in this
      group. These findings may be important in determining the relationship between
      obesity and cardiovascular risk factors at pediatric age.

PMID- 12008688
TI  - Mutations of the 5alpha-steroid reductase type 2 gene in six Turkish patients
      from unrelated families and a large pedigree of an isolated Turkish village.
AB  - We describe six Turkish patients with 5alpha-steroid reductase type 2 deficiency
      from unrelated Turkish families and a large pedigree of one of these patients who
      reside north-west of Anatolia. Patients NA, KS, BD and SY presented for
      evaluation of bilateral inguinal masses with female phenotypes. Patient ABE had
      penoscrotal hypospadias with male phenotype. Homozygous mutation of the 5alphaSR2
      gene was identified in five of these patients by genomic DNA analysis. These
      mutations were Leu55Gln in exon 1 (in patients FG, BD and ABE), deltaMet157 in
      exon 3 (in patient NA), and splice junction abnormality in intron 1 (in patient
      SY). One individual (patient KS) was found to be a compound heterozygous carrier
      of two different mutations, Leu55Gln in exon 1 and Arg171Ser in exon 3. Patient
      FG had a large pedigree with the Leu55Gln mutation in exon 1. The pedigree of
      this family with marital consanguinity is remarkable, and possibly due to the
      isolation of this family because of economic and social problems. A further 85
      individuals belonging to this family were analyzed for exon 1 Leu55Gln mutations
      in the 5alphaSR2 gene. Forty-two of these 85 individuals (49.41%) had this
      alteration; 11 were homozygous (8 genetic male, 3 genetic female) and 31
      heterozygous (18 genetic male, genetic female) for this mutation. It was
      interesting to see asymptomatic homozygous female carriers. In conclusion,
      according to our results and those of other Turkish patients reported by
      different investigators, 5aSR2 gene mutation analysis, especially for Leu55Gln in
      exon 1 and deltaMet157 in exon 3, must be carried out in Turkish patients with
      male pseudohermaphroditism. Homozygous asymptomatic female carriers must be taken
      into consideration in this clinical entity, especially in a closed population,
      because of the risk of transmitting the disease to their offspring.

PMID- 12008689
TI  - Etiology, clinical profile, gender identity and long-term follow up of patients
      with ambiguous genitalia in India.
AB  - There is little information on the profile of children with ambiguous genitalia
      in India. Presented here is an analysis of patients with ambiguous genitalia
      registered in a general endocrine clinic during the last 2 decades. Seventy-four
      patients (age 4 months to 36 years) were registered during this period. Fifty-two
      were more than 5 years old at the time of registration. Thirty-five were reared
      as females, 29 as males; nine children (4 months to 1 year old) were brought for
      sex assignment, and one (with epispadias) was brought for correction of urinary
      incontinence. Investigations revealed 28 patients with congenital adrenal
      hyperplasia, 14 dysgenetic male pseudohermaphroditism, ten true hermaphroditism,
      six partial androgen insensitivity, four castration and one epispadias. There
      were eight patients with perineal hypospadias with normal Leydig cell reserve
      (normal LH, FSH and testosterone response to LHRH). Sex of rearing and gender
      identity were concordant in all except the patients with perineal hypospadias
      with normal Leydig cell response. These observations support the theory that
      prenatal androgen exposure masculinizes the brain.

PMID- 12008690
TI  - Early menarche and subclinical ovarian hyperandrogenism in girls with reduced
      adult height after low birth weight.

PMID- 12008691
TI  - Treatment with flutamide decreases cortisol clearance: implications for therapy
      in congenital adrenal hyperplasia.
AB  - BACKGROUND: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency
      is characterized by a defect in cortisol and often aldosterone secretion, and
      adrenal hyperandrogenism. Current treatment is to provide adequate glucocorticoid
      and mineralocorticoid substitution to prevent adrenal crises and to suppress
      excess adrenocortical androgen secretion. Anti-androgen therapy with flutamide is
      an option that allows control of hyperandrogenism without recourse to
      supraphysiological doses of glucocorticoid. METHODS: We examined the
      pharmacokinetic parameters of hydrocortisone administered i.v. as a bolus at a
      dose of 15 mg/m2 in a 17.3 year-old female patient with classic CAH before and
      four weeks after institution of flutamide treatment by determining serum cortisol
      concentrations at 10 min intervals for 6 h following the i.v. bolus of
      hydrocortisone. RESULTS: Treatment with flutamide resulted in a decrease in
      cortisol clearance from 420 ml/l to 305 ml/l (27% reduction), and a decrease in
      volume of distribution from 51.61 to 451 (12.9% reduction). The half-life of
      cortisol increased from 85.3 min to 102.1 min. CONCLUSIONS: Flutamide treatment
      decreases cortisol clearance, thereby prolonging its half-life. These findings
      indicate that a reduction in the daily dose of glucocorticoid replacement may
      need to be considered when flutamide is added to the treatment regimen of
      patients receiving hydrocortisone.

PMID- 12008692
TI  - Triglyceride-induced diabetes mellitus in congenital generalized lipodystrophy.
AB  - High levels of triglycerides and free fatty acids have been implicated in the
      pathogenesis of type 2 diabetes mellitus (DM). Congenital generalized
      lipodystrophy (CGL) is an autosomal recessive syndrome characterized by intense
      whole body reduction of subcutaneous fat. Its clinical manifestations appear
      during the first years of life. However, DM is usually a late event. We report a
      patient with CGL, diagnosed at 4 months of age, who has severe
      hypertriglyceridemia (serum triglyceride 12.34 mmol/l and cholesterol 3.90
      mmol/l), muscular hypertrophy, hepatomegaly and DM (fasting glycemia 25.9
      mmol/l). Hepatic biopsy revealed steatosis and fibrosis. A modified normolipidic
      (composed of medium chain triglycerides) normocaloric normoproteic milky diet and
      insulin therapy were instituted. After 1 month treatment a reduction of serum
      glucose and triglyceride levels (4.13 mmol/I and 7.7 mmol/l, respectively) was
      noted, with later normalization, which led to the discontinuation of insulin
      therapy. The patient has been maintaining good control with diet alone,
      presenting normal serum lipid levels (triglycerides 1.07 mmol/l, total
      cholesterol 2.71 mmol/l) and the following glycemic profile at OGTT: 0' 4.4
      mmol/l; 30' 7.0 mmol/l; 60' 3.8 mmol/l; 90' 5.3 mmol/l, and 120' 5.2 mmol/l. The
      disappearance of hepatic steatosis was evidenced by a biopsy obtained 1 year
      after the beginning of treatment. In conolusion, this report suggests that the DM
      occurring in CGL can be precipitated by high triglyceride levels.

PMID- 12008693
TI  - Feminizing Sertoli cell tumor associated with Peutz-Jeghers syndrome.
AB  - Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by
      the association of mucocutaneous pigmentation and multiple gastrointestinal
      hamartomatous polyps and with an increased risk of developing gonadal sex tumors
      besides other malignancies. We describe a 7 1/2 year-old boy with PJS and
      bilateral gynecomastia. He has had buccal pigmentation since 1.5 years and had
      been operated for rectal polyp excision at 3.5 years. On physical examination,
      his height was at the 90th percentile, and his height age and bone age were 9 and
      10 1/2 years, respectively. Increased melanotic buccal pigmentation of the lips
      and bilateral gynecomastia were noticed. Both of the testes were firm, non-tender
      and smooth on the surface, and each measured 8 ml. Hormonal measurements were all
      in the prepubertal range. Testis ultrasonography showed bilateral hyperechogenic
      areas within the glands. When he was operated for invagination and an ileum
      segment full of polyps was resected, bilateral testicular biopsies were also
      performed. Histopathological evaluation of the testes revealed bilateral
      multicentric benign Sertoli cell tumors. The aromatase inhibitor testolactone was
      started to slow skeletal maturation. On the basis of this and previous reports,
      PJS associated with sex-cord tumors is increasingly recognized in males as well
      as in females.

PMID- 12008694
TI  - [Iodine deficiency and other potential goitrogens in the persistence of endemic
      goiter in Mexico].
AB  - OBJECTIVE: To measure the frequency of goiter and the presence of potential
      goitrogens in a sample of school-age children and pregnant women. METHODS: Cross
      sectional study in a purposive sample in three regions, one with known high
      prevalence of goiter (Huejutla), one with unknown prevalence (Ixmiquilpan) and
      one with no expected deficiency (Pachuca). Children were sampled from schools and
      pregnant women from rural reference hospitals. Goiter was evaluated by manual
      exam and ultrasound. RESULTS: Goiter prevalence in 673 children between 6 and 14
      years old was 8% in Pachuca, 9% in Ixmiquilpan, and 14% in Huejutla. In 300
      pregnant women, goiter prevalence was 19% in Pachuca, 20% in Ixmiquilpan, and 52%
      in Huejutla. In 936 interviews on salt consumption, 98% of families consumed
      table salt, but only 50% of the samples were adequately iodized. Twenty-four
      percent of families obtained water from wells contaminated with arsenicum and
      mercury in Pachuca and Ixmiquilpan, and with colibacilli in Ixmiquilpan.
      CONCLUSIONS: Even at the end of the millenium, endemic goiter is still a public
      health problem in this sample of school-age children and pregnant women. Despite
      consumption of iodized salt, ingestions of goitrogens may be contributing to the
      persistence of this problem.

PMID- 12008695
TI  - [Two platelet inhibitors after acute coronary syndrome. Many colleagues are not
      aware of this].

PMID- 12008696
TI  - Improved method for visualizing coated pits, microfilaments, and microtubules in
      cryofixed and freeze-substituted plant cells.
AB  - We have optimized the conditions for visualizing microfilaments, microtubules,
      and coated pits in the cortical cytoplasm of high-pressure frozen and freeze
      substituted plant cells, in both tobacco root tips and onion cotyledons,
      individual microfilaments and the supramolecular structure of coated pits can be
      seen clearly in freeze-substituted samples treated with OsO4 at 40 degrees C
      followed by 5% uranyl acetate. Treatment with uranyl acetate alone resulted in
      poorly stained cytoplasmic organelles, whereas microfilaments were difficult to
      discern in specimen treated with OsO4 alone. The combination of a 40 degrees C
      OsO4 staining step followed by staining with uranyl acetate at 4 degrees C should
      prove useful for more detailed plant cytoskeletal/membrane studies in the future.

PMID- 12008697
TI  - Postprocedure ischemic events after treatment of intracranial aneurysms with
      Guglielmi detachable coils.
AB  - OBJECT: Ischemic stroke or transient ischemic attack (TIA) may occur after the
      treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The
      purpose of the present study is to investigate possible risk factors for
      thromboembolic events and to determine their frequency and time course. METHODS:
      The records of 178 consecutive patients with 193 treated intracranial saccular
      aneurysms were reviewed. A total of 159 GDC procedures were performed to treat
      143 aneurysms in 133 of those patients who were in good neurological condition,
      allowing clinical detection of postprocedure ischemic events (TIA or stroke). The
      association of clinical, anatomical, and pharmacological factors with
      intraprocedure intraarterial thrombus and with postprocedure ischemic events was
      investigated by using uni- and multivariate analyses. Thrombus protruding into
      the parent artery was noted during six of 159 GDC procedures, resulting in a
      clinical deficit in one patient. No factor was associated with intraprocedure
      intraarterial thrombus. Ten postprocedure ischemic events occurred in nine
      patients. Seven events occurred within 24 hours, and three events occurred
      between 24 hours and 58 days. Aneurysm diameter and protruding coils were
      significant independent predictors of postprocedure ischemic events in
      multivariate analysis (both p = 0.02). The actuarial risk of stroke was 3.8%.
      CONCLUSIONS: Larger aneurysm diameter and protruding loops of coils are
      associated with postprocedure ischemic events after GDC placement. It is unlikely
      that GDC-treated aneurysms retain thromboembolic potential beyond 2 months.

PMID- 12008698
TI  - Genetic effects of cosmic radiation on bacteriophage T4Br+ (on materials of
      biological experiment "Soyuz-Apollo").
AB  - During the experiment "Spore-ring Forming Fungi Biorhythm" of the Apollo-Soyuz
      test project the Rhythm-1 apparatus contained a dried film culture of
      bacteriophage T4Br+, growing cultures of Actinomyces and plastic nuclear particle
      detectors. The following were studied: the frequency of induction of r mutations
      in the bacteriophage film per 2 X 10(4) surviving particles, the spectrum of
      mutant types obtained (rI, rII, rIII), and the possible molecular mechanisms for
      the occurrence of rII mutants with due regard to the registered tracks of heavy
      nuclear particles. The studies showed that the local radiation due to heavy
      nuclear particle tracks plays a major role in space radiation damage.

PMID- 12008699
TI  - The action of space flight factors on the radiation effects of additional gamma
      irradiation of seeds.
AB  - The action of space flight factors (SFF) on radiosensitivity and the effects of
      preflight irradiation of air-dried Crepis capillaris (L) Wallr and Arabidopsis
      thaliana (L) Heynh seeds aboard the spaceships of the Cosmos, Soyuz and Salyut
      series was studied. The results have shown that vibration and linear acceleration
      (VA) cause damage of the meristematic embryonic cells and simultaneously decrease
      the radiosensitivity of seeds. SFF enhance the effect of preflight gamma
      irradiation of seeds with respect to a number of characteristics. This can be
      explained partly by the action of VA. The basis of all observed effects is
      chromosomal aberrations which are expressed in a series of successive cell
      divisions and which decrease the survival and fertility of plants that grow from
      flight-exposed seeds.

PMID- 12008700
TI  - Preliminary results of Cytos experiment flown in Salyut VI: investigations on
      Paramecium aurelia.
AB  - The purpose of the Cytos experiment was to investigate a possible effect of space
      flight on cell proliferation kinetics. Cultures of Paramecium aurelia
      successively maintained at a temperature of 8 degrees and 25 degrees C were fixed
      every twelve hours during the orbital flight. Space flight resulted in a
      stimulating effect on cell proliferation, an increase in cell volume and changes
      in the ionic components of the culture medium.

PMID- 12008701
TI  - Gravity as a biochemical determinant.
AB  - The existence of obvious morphological and physiological changes in living
      systems exposed to altered gravity immediately informs us that prior changes have
      taken place in the chemistry of exposed cells, tissues and organs. These changes
      include transients that return more or less promptly to the norm when the system
      is restored to the terrestrial g-field. For example, altered serum hormone and
      electrolyte levels in man, which appear to reflect successful adaptation to the
      conditions of orbital weightlessness, disappear shortly after return to Earth.
      Other changes--in mineral and protein constituents of the skeletal system in man,
      and cell wall composition in plants--are more persistent or even permanent.
      Hypogravitational departures from the norm include not only "weightlessness" as
      achieved in orbit, but also experimental modes of compensation, on the clinostat
      or by flotation. These techniques are useful in the study of hypogravity but
      cannot replace fully the weightless environment. Plant ethylene and peroxidase
      both increase under orbital, clinostat and/or flotation conditions whereas 3
      phosphoglyceraldehyde-dehydrogenase increases under orbital but not clinostat
      conditions; cytochrome reductase and malic dehydrogenase levels are affected by
      the clinostat, but not by actual weightless conditions. How do the altered
      organismal biochemistries induced by the centrifuge and the clinostat relate to
      one another? Does gravity operate on living systems as a continuous variable from
      0 to superterrestrial values, or do deviations from g(earth) generate non
      uniform, discontinuous stress responses, irrespective of sign? In plants,
      measurements of wall lignin content and peroxidase activity yield opposite
      answers. Given the limited data so far available we will consider the meaning of
      these contradictions.

PMID- 12008702
TI  - A model for vestibular function in altered gravitational states.
AB  - During evolution, the vestibular organ was made to serve mainly two purposes: 1)
      to guide eye movements during sharp turns, so that the point of fixation in the
      visual field can be kept steady, a function accomplished by the semicircular
      canal system and 2) to indicate the terrestrial vertical, so that upright posture
      and gait can be maintained even in the dark. The otolith system serves the latter
      purpose. Since the function of the semicircular canal system does not depend on
      gravity, it is not grossly disturbed by gravitational levels different from 1 g.
      The proper function of the otolith system depends entirely on the presence of a
      gravitational force vector of 9.8/m/sec2 directed towards the center of the
      earth. This system therefore malfunctions when the amplitude of the combined
      gravito-inertial load is different from 1 g and also when the direction of the
      sensed gravitational pull is "contaminated" by additional inertial reactive
      forces as during horizontal acceleration. The effect of such inertial
      stimulations is probably even stronger in a weightless environment, in which case
      the background stimulation of terrestrial gravity is absent. Moreover, minor mass
      differences between the otolithic membranes of the left and right inner ear, even
      if well compensated on the ground, might lead to malcompensation in
      weightlessness as well as in hypergravity. A hypothetical model is developed to
      describe in the central nervous system compensating mechanisms in hypo- and
      hypergravitational states. The "space-sled" is introduced as a new research tool
      and recommendations are made for a prophylactic training regimen to reduce or
      prevent space sickness.

PMID- 12008703
TI  - Physiological effect of high, sustained +Gz forces on man.
AB  - Two studies were conducted to evaluate physiological responses and possible
      tolerance to high sustained +Gz forces at the USAF School of Aerospace Medicine,
      using the 20-ft (6.10 m) radius Human Centrifuge. In the first study (A), 14
      human volunteer subjects--fully protected with an anti-G suit and performing the
      M-1 or L-1 straining maneuver--were exposed to +Gz forces. These forces began at
      +6.5 Gz, and increased weekly in 0.5 G increments to +9.0 Gz, for a duration of
      45 sec at each level. Physiological performance was based mostly on the subjects'
      ability to maintain clear vision during the 45 sec exposure. Of the 14 subjects,
      9 were able to maintain vision and remain at the +9 Gz level for 45 sec. In the
      second study (B), 12 human volunteer subjects--also protected with anti-G suits
      and using the straining maneuvers--were exposed to levels of +1, 3, 6, and 8 Gz,
      for 60 sec at each level. Extensive physiologic parameters were recorded in order
      to detect objective criteria which could be used as determinants for a medical
      tolerance endpoint to the particular level of +Gz stress. In both studies, the
      reasons for stopping the runs at levels exceeding +7.5 Gz included: fatigue,
      cardiac arrhythmias, blackout, and one occurrence of ventricular tachycardia.
      Other physiological responses to the sustained +Gz stress (such as heart rate,
      arterial blood pressure, central venous blood pressure, arterial oxygen
      saturation, gastric pressure, and ankle venous pressure) did not furnish specific
      information that could be used as "physiological tolerance limit" criteria.

PMID- 12008704
TI  - Prophylactic [correction of prophylatic] effects of intermittent acceleration
      against physiological deconditioning in simulated weightlessness.
AB  - The prophylactic effect on adult human males of intermittent acceleration against
      physiological deconditioning in weightlessness simulated by water immersion was
      studied at +0.8, +1.2, and +1.6 g. These prophylactic exposures reduced renal
      excretion of fluid and plasma volume changes, and increased venous compliance and
      the time at which the subjects could tolerate an acceleration field of +3 g.

PMID- 12008705
TI  - Continuous metabolic and cardiovascular measurements on a monkey subject during a
      simulated 6-day Spacelab mission.
AB  - In May 1977 the NASA Ames Research Center and NASA Johnson Space Center jointly
      conducted a test of the feasibility of performing various types of biological and
      medical experiments during future Spacelab flight missions. One of the
      experiments was designed to examine the effects of weightlessness on several
      basic parameters of metabolic and cardiovascular function in an adult nonhuman
      primate. The subject animal, a 10 kg male pig-tailed monkey (Macaca nemestrina),
      was prepared 3 months before the test with a surgically implanted NASA/Ames
      biotelemetry unit to provide continuous measurements of body temperature and
      selected cardiovascular parameters. Three days before the simulated "launch" the
      animal was inserted into a fiberglass pod system to provide continuous
      measurement of respiratory gas exchange. The pod system was installed in a
      Spacelab mock-up and all physiological data channels were recorded continuously
      for 2.6 days prior to "launch", for 6.3 days during "flight", and for 1.8 days
      after "landing". The experiment was tended entirely by the Spacelab flight crew
      during the "flight" period. Statistically significant diurnal variation was noted
      in oxygen consumption and carbon dioxide production rates, body temperature and
      heart rate, but not in respiratory quotient or blood pressure. A transient
      increase of the parametric values was noted during the latter portion of the
      "flight" period, possibly occasioned by increased flight crew activity. The high
      quality of the continuous data obtained during the 10.7-day total experiment
      period demonstrates the feasibility of performing sound physiological
      experimentation on nonhuman primates in the Spacelab environment.

PMID- 12008706
TI  - The gastrointestinal tract in hypokinetic rats.
AB  - In Wistar rats kept for 15, 30 and 60 days in a hypokinetic state in special
      cages, alteration of some gastrointestinal glands was studied by means of
      histochemical and electron microscopic methods. After 15-30 days of hypokinesia,
      a decrease was found in the muco-polysaccharide content of the submaxillary,
      gastric and duodenal glands. The intestinal goblet cells appeared vacuolated. The
      oxyntic cells, which secrete HCl, as well as the G antral cells, which secrete
      gastrin, were in an active state. The hypokinetic rats exhibited increased
      gastric secretion. The electron microscopic aspect of the principal cells
      corresponded to augmented pepsin secretion. The enterocytes showed an increase in
      their leucine aminopeptidase, acid phosphatase and glucose-6-phosphatase content.
      In the submucosa of the fundus of the stomach an accumulation of eosinophils was
      observed. These modifications were more striking after 15 than after 30 days, and
      disappeared after 60 days of hypokinesia. These morphological and functional
      changes may be explained by glucocorticoid hypersecretion corresponding to a
      stress reaction.

PMID- 12008707
TI  - Changes in enzymes and potassium content of the neuromuscular systems of albino
      rats during prolonged exposure to simulated hypogravics.
AB  - With respect to neuromuscular function, aldosterone activity, enzymatic and
      potassium (K) metabolism of organ tissues were investigated during the stress and
      adaptation stabilized phases of hypodynamically stressed rats. During adaptation,
      muscle tissue enzymes, such as aldolase, showed no change until the 35th day. The
      decrease of succinic dehydrogenase (SDH) was evident at 7 days. Lactic
      dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels increased
      transiently on the 18th day; this implied the development of muscular atrophy. A
      decrease in the 42K uptake of muscle was found from the 18th day onward. In the
      brain, a progressive decrease of aldolase was observed. 42K uptake showed no
      change in the brain, but the K content increased at both 7 and 18 days of
      exposure. The increase of cholinesterase (ChE) was more remarkable in the brain
      than in muscle, although transient. We suggest that the brain plays an important
      part in the adaptation process, through increasing or maintaining the functions
      of the neuromuscular excitation system during the 7-18 days of hypodynamic
      exposure.

PMID- 12008708
TI  - Hypergravity: its effect on the estrous cycle and hormonal levels in female rats.
AB  - Hypergravity at 1.02-2.28 g was simulated by centrifugation and the estrous
      cycles of rats were followed by testing vaginal smears. Associated hormonal
      changes were measured from blood samples by radioimmunoassay. It was found that
      moderate hypergravity affects the estrous cycle by prolonging the diestrous
      period, and this effect seems to bear a direct relationship to the strength and
      timing of the hypergravity. Intermittent centrifugation produces the same effect
      as continuous centrifugation. After the prolonged diestrous, the estrous cycle
      returns to normal. The observed effects were associated with hormonal changes.
      Progesterone was elevated during the prolonged diestrous although no consistent
      changes in estrogen levels could be found. The effect of simulated hypergravity
      resembles the pseudo-pregnancy response produced in rats by various stimuli, but
      a decidual reaction, i.e., the usual uteral growth as a response to pregnancy or
      injury during pseudo-pregnancy, could not be elicited during the prolonged
      diestrous induced by 2.08 g. The possible mechanism eliciting the prolongation of
      diestrous is discussed.

PMID- 12008709
TI  - Effect of gravity on lymphocyte proliferation.
AB  - Reports on postflight examination of lymphocytes from crew members of soviet and
      american spaceships show a depression of reactivity towards mitogens in vitro.
      The purpose of this communication is to present experimental evidence that
      gravity can interfere with lymphocyte activation. Lymphocytes were incubated in
      the presence of concanavalin A in a centrifuge at 2 and 4 g for four days. This
      environment causes a significant acceleration of the response to the mitogen. In
      addition, remarkable differences in the ultrastructure of cells grown at 1 g and
      4 g are observed by electron microscopy. This investigation is related to the
      experiment "Effect of weightlessness on lymphocyte proliferation" experiment
      which will be performed during the first Spacelab mission.

PMID- 12008710
TI  - Rat growth during chronic centrifugation.
AB  - Female weanling rats were chronically centrifuged at 4.15 g with controls at
      terrestrial gravity. Samples of 6 to 10 rats were sacrificed for body composition
      studies at 0, 28, 63, 105, 179 and 308 days of centrifugation and 57 days after
      centrifugation ended. The centrifuged group had a significantly lower mature body
      mass than the controls (251 vs 318 g) but the rate of approach to the mature
      values was the same in both groups. Retirement to 1 g on the 60th day resulted in
      complete recovery. Masses of muscle, bone, skin, CNS, heart, kidneys, body water
      and body fat were changed in the centrifuged group. However, an analysis of the
      growth in mass of individual components relative to growth of the total fat-free
      compartment revealed that only skin (which increased in mass) was responding to
      centrifugation per se.

PMID- 12008711
TI  - Studies of amino acid metabolism in the muscles of rats flown aboard the
      biosatellite Cosmos 782.
AB  - Space flight induced an increase in the content of free isoleucine, leucine,
      phenylalanine, tyrosine, and valine and a decrease of free threonine and glycine
      in the quadriceps muscle of the rat. The content of the individual free amino
      acids returned to their control values by the 25th postflight day. The total
      content of free amino acids remained unaltered from the control values. In the
      ground-based synchronous experiment the content of most free amino acids
      increased on the first and decreased on the 25th post-experimental day. These
      findings suggest that weightlessness induces development of protein catabolism in
      muscular tissue. However, the developments are compensatory with respect to total
      free amino acid content.

PMID- 12008712
TI  - Influence of the ambient acceleration field upon acute acceleration tolerance in
      chickens.
AB  - It has been demonstrated both in the Russian and in the American space programs
      that there is a progressive deconditioning of the circulatory system with
      exposure to weightlessness. Astronauts and cosmonauts returned to Earth have a
      significantly reduced orthostatic tolerance which will persist for a few days. We
      have measured the acceleration tolerance of domestic fowl, acutely exposed to a 6
      g+z field, as the time over which a normal heart rate can be maintained. This
      period of circulatory accommodation ends abruptly with a marked bradycardia,
      which with continued treatment is terminal. For animals which have been
      previously chronically accelerated (e.g., physiologically adapted to a 2.5 g
      field) the acute acceleration tolerance is greatly increased. It appears that the
      influence of the ambient acceleration field in conditioning the responsiveness of
      the circulatory system is a general phenomenon.

PMID- 12008713
TI  - Biological investigations on the orbital station "Salyut-5".
AB  - Genetic and embryological investigations were continued on the orbital station
      Salyut-5. The effect of space flight factors on dry Crepis capillaris (L) Wallr
      seeds and seedlings, dry Arabidopsis thaliana (L) Heynh seeds, Polyporus brumalis
      Pers. ex. Fries culture as well as on spawn development and fish behaviour was
      studied. Space flight factors are shown to have adverse effects with respect to
      some characteristics in seeds and seedlings, and to change the morphology of the
      fungus. Fishes appear to adapt themselves to weightlessness.

PMID- 12008714
TI  - Hornet building orientation in a vertically rotating centrifuge.
AB  - Hornets build combs that are clearly oriented toward the center of gravity and
      they compensate for any change made in the direction of their cells, provided the
      gravitational vector remains unchanged. Under natural conditions the first few
      cells are built by the queen in the spring, following the hibernation period, and
      building is then continued by the workers. Recently several reports have been
      published concerning the fact that groups of hornets (V. orientalis workers) may
      build in the absence of the queen and that such combs resemble those built by the
      queen. In previous investigations on building orientation, hornets placed in
      artificial breeding boxes (ABBs) on a horizontal centrifuge were subjected to
      constant centrifugal and gravitational forces, the resultant of which ranged
      between 1-1.5 g. Under these conditions young hornets (1-2 days of age) built
      combs in the direction of the resultant force, while the direction of building by
      adult hornets (3-7 days of age) was dependent on the presence or absence of a
      straight roof. Adults placed in the ABBs of rectangular shape built combs the
      orientation of which was determined by the Earth's gravity alone (perpendicular
      to the roof) whereas those in spherical ABBs with a convex roof built combs in
      the direction of the resultant gravitational and centrifugal forces, much the
      same as combs built by the young hornets. We were, however, also interested in
      studying the building orientation of hornets placed under conditions of changing
      resultant forces. The present paper describes comb building by hornets under the
      alternating gravitational forces of a vertical centrifuge.

PMID- 12008715
TI  - Computer simulation of circumnutations--behaviour under different g's and
      comparison with experiment.
AB  - The influence of different g-forces on helical growth movements--circumnutation-
      of sunflower seedlings is treated. Predictions from a model, describing the
      movements as geotropic overshoot movements, are given. Results from tests of the
      assumptions are given. These results as well as results in the literature do not
      contradict the model. The need for more precise centrifuge tests under otherwise
      free fall conditions is emphasized.

PMID- 12008716
TI  - Is gravity a morphological determinant in plants at the cellular level?
AB  - It is not yet known whether higher plants, which have evolved in a gravity
      oriented environment, can reproduce normally or develop via single cells (somatic
      or zygotic) and pass normally through all phases of development, tissue
      differentiation and reproduction through consecutive generations at near-zero g.
      Most published work deals with directional gravitational stimuli (geotropisms) as
      they operate on the subsequent growth of preformed plant organs that have
      acquired the ability to perceive and respond to gravity during development at 1
      g. But it should be established whether plant development can proceed normally in
      the weightless state, especially that critical stage in which single cells
      produce multicellular units leading to embryos with the growing regions of shoot
      and root which, in turn, give rise to all the tissues of the plant body. We
      consider here an experiment that tested whether carrot embryos, capable of
      developing from cultured somatic cells, could do so under conditions of near
      weightlessness. Space flight seemed to have no adverse affects on the induction
      of such embryos or on the initiation of their organs. But there are still
      reservations which are discussed. Other systems adaptable to the study of
      embryogenesis and development in space and to resolve the current reservations
      are described and their place in future space research is indicated.

PMID- 12008717
TI  - Responses of roots to simulated weightlessness on the fast-rotating clinostat.
AB  - Sedimentable cell particles are distributed randomly along the horizontal axis of
      the fast-rotating clinostat. They neither sediment in the direction of gravity,
      nor in the direction of the centrifugal force, nor in the direction of the
      resultant force of both. The effect of this "weightlessness" and that of very
      small centrifugal forces on the perception of mass acceleration was examined
      using young primary roots of Lepidium sativum L. (Cruciferae) during their early
      development on the fast-rotating clinostat. The results of the experiments show:
      1) there is no response of the roots in the direction of gravity, 2) at small
      centrifugal forces (< 2.2 x 10(-2) g) a curvature response occurs in the
      direction of the stimulus, 3) the threshold value for the perception of mass
      acceleration lies at 4.3 x 10(-3) g, and 4) below the threshold value the
      existence of an autonomous root curvature has been proved for the first time,
      which is not caused by mass acceleration.

PMID- 12008718
TI  - Effects of simulated hypogravity on respiration and photosynthesis of higher
      plants.
AB  - Clinostat rotation about a horizontal axis mechanically cancels the directional
      component of the gravity force vector which is biologically sensed by plants.
      However, efficiency of clinostats as simulators of weightlessness for prolonged
      periods has not been demonstrated conclusively. Morphological appearance of
      plants in orbital flight may resemble their counterparts on earth-based
      clinostats, but physiological responses may differ. Photosynthesis experiments
      with algae have been performed in satellites orbiting the earth, but similar
      experiments with higher plants have not been conducted. This paper describes an
      experimental apparatus for measurement of photosynthetic and respiratory rates of
      whole plants on rotating clinostats. Initial experiments show an enhancement of
      gas exchange during rotation about a horizontal axis.

PMID- 12008719
TI  - Biological experiments carried out aboard the biological satellite Cosmos-936.
AB  - Experiments to study the effect of weightlessness on the emergence and
      development of cell organelles and genetic structures were carried out during
      18.5 days aboard the biological satellite Cosmos-936. The experiments were
      conducted on the fruit fly Drosophila melanogaster Orgeon-R. Their purpose was to
      investigate possible chromosomal aberrations and gene mutations in the sex
      chromosomes of males and females. The investigations showed that the frequency of
      mutations in the progeny of specimens exposed to weightlessness did not differ
      from the controls. The experiments with higher plants were performed on the
      seedlings of Crepis capillaris and Zea mays grown from seeds aboard the
      biosatellite. The cytological examination of Crepis capillaris chromosomes
      demonstrated that there were no structural chromosome changes in the experimental
      and control variants. Maize seedlings grown in weightlessness and examined later
      in the laboratory showed that cells of the root meristem cultivated in
      weightlessness were much larger than the controls. Mitochondria of seedlings
      exposed to weightlessness were swollen and had a low content of membranous
      material.

PMID- 12008720
TI  - Influence of orbital flight conditions on formation of genitals in Muscari
      racemosum and Anethum graveolens.
AB  - It was shown that under space flight conditions development of male genitals in
      Muscari racemosum is accelerated compared to that of laboratory and natural field
      controls. Conditions of space flight produced an inhibitory effect on germination
      and germinative energy of Anethum graveolens seeds. The first stages of the plant
      development, right up to the flowering stage, also suffered from the inhibitory
      influence of space flight conditions. A cytoembryological study of the experiment
      and control plants found no essential differences between them.

PMID- 12008721
TI  - Medicare is likely to pay for anticancer drugs.

PMID- 12008722
TI  - Broadcast of star's colonoscopy puts up screening by 20%.

PMID- 12008723
TI  - Caesarean section rate in England reaches 22%.

PMID- 12008724
TI  - Scottish expert group finds no link between MMR and autism.

PMID- 12008725
TI  - Australia's public hospitals are under pressure as doctors transfer patients
      because of insurance crisis.

PMID- 12008726
TI  - Does risk homoeostasis theory have implications for road safety. Against.

PMID- 12008727
TI  - Tired surgical trainees. Specialist registrars working in district general
      hospitals often travel considerable distances while tired.

PMID- 12008728
TI  - Researching outcomes of educational interventions. Initial formation of unbiased
      groups is most important issue in randomised controlled trials.

PMID- 12008729
TI  - Over the counter cough medicines for acute cough. Good quality research is
      needed.

PMID- 12008730
TI  - Over the counter cough medicines for acute cough. Gap exists between practice and
      research.

PMID- 12008739
TI  - The a posteriori probability of a kidney cancer cluster attributed to
      trichloroethylene exposure.

PMID- 12008740
TI  - Canadian hot weather health-response plan.

PMID- 12008741
TI  - [Neuropathy with hereditary liability to pressure].

PMID- 12008742
TI  - [Dementia paralytic as presenting form of syphilis].

PMID- 12008743
TI  - [Absence of anticysticercus antibodies in the cerebrospinal fluid of Cuban
      pediatric patients with convulsions].

PMID- 12008744
TI  - Molecular and cellular mechanisms of mechanical stress-induced cardiac
      hypertrophy.
AB  - Congestive heart failure is one of the major issues for cardiologists. Since
      cardiac hypertrophy deteriorates into heart failure, it is important to elucidate
      the mechanisms of cardiac hypertrophy. Hemodynamic overload, namely mechanical
      stress, is a major cause for cardiac hypertrophy. Mechanical stress induces
      various hypertrophic responses such as activation of phosphorylation cascades of
      many protein kinases, expression of specific genes and an increase in protein
      synthesis. During this process, secretion and production of vasoactive peptides
      such as angiotensin II and endothelin-1, are increased and play critical roles in
      the induction of these hypertrophic responses. Recently, a Ca2+ dependent protein
      kinase, CaMK, and a Ca2+ dependent protein phosphatase, calcineurin, have
      attracted great attention as critical molecules that induce cardiac hypertrophy.
      In this review, we described the mechanisms by which mechanical stress induces
      cardiac hypertrophy, especially focusing on the role of calcineurin in the
      development of cardiac hypertrophy.

PMID- 12008745
TI  - A case of growth hormone and gonadotropin deficiency associated with unilateral
      anophthalmia, microphallus, cryptorchidism, and mental retardation.
AB  - We report a rare case of growth hormone and gonadotropin deficiency associated
      with dysmorphic features. A 16-year-old boy had left anophthalmia, microphallus,
      bilateral cryptorchidism, and mental retardation. His chromosomal karyotype was
      normal, 46, XY. Endocrinological studies revealed growth hormone and gonadotropin
      deficiency, attributed to hypothalamic dysfunction. Magnetic resonance imaging
      scan of the head showed a hypoplastic pituitary gland, decreased high intensity
      signals in the pituitary posterior lobe, absence of the left eye, and a
      hypoplastic left optic nerve with no abnormality of the pituitary stalk, corpus
      callosum, or septum pellucidum. Although not completely consistent with the
      features of septo-optic dysplasia (SOD), his condition was considered within the
      spectrum of SOD. Despite similarities to the Hesx1 knockout mouse, a model of
      human SOD, mutation analyses revealed no mutations or polymorphisms in coding
      regions of any exons or intron-exon boundaries of the HESX1 gene. Further genetic
      studies of this patient may improve understanding of molecular mechanisms
      involved in pituitary development.

PMID- 12008746
TI  - Impact of polymorphisms of human beta-adrenergic receptor gene on changes in
      height during growth hormone treatment.
AB  - The aim of this study was to investigate the occurrence of polymorphisms of the
      beta-adrenergic receptor gene in short children and to evaluate the possible
      influence of the polymorphisms on changes in height and obesity index in response
      to GH treatment. Of the 75 children enrolled in the study, 40 completed at least
      5 years of GH treatment. The genotype distribution of the beta2 and 3-adrenergic
      receptor polymorphisms in the study population did not differ significantly from
      those reported in non-obese subjects. There were no significant differences in
      the SD score for height at any given time-point between the group with and
      without the Trp64Arg mutation of the beta3-adrenergic receptor gene. In relation
      to the Glyl6Arg polymorphism of the beta2-adrenergic receptor gene, the mean SD
      score for height increased significantly during GH treatment in children with
      Argl6Arg and Glyl6Arg. In those with Glyl6Gly, the score did not show any
      significant increase during all 5 years of GH treatment. In both the groups with
      and without the Trp64Arg mutation, the changes in obesity index did not reach
      statistical significance at any time-point. Only children with Glyl6Gly had a
      significantly higher baseline mean obesity index than those with Glyl6Arg. The
      index also decreased markedly from 21.9% to 5.8% in these children during the
      first 4 years of GH treatment. Thus, when the impact of the polymorphisms of
      these two receptor genes was studied simultaneously, it appeared that only the
      beta2-adrenergic receptor polymorphism had an important role to play in
      modulating the regulation of growth rate and energy expenditure in short
      children.

PMID- 12008747
TI  - Retrospective analysis of 18 cases of antithyroid drug (ATD)-induced
      agranulocytosis.
AB  - In this study, we retrospectively analyzed 18 patients in whom antithyroid drug
      (ATD)-induced agranulocytosis developed during treatment of Graves' disease. All
      patients were more than 20 years of age, and we saw no correlation between age
      and the development of agranulocytosis. In 17 of 18 patients, ATD-induced
      agranulocytosis developed within 2 to 12 weeks of starting ATD treatment.
      Development of agranulocytosis was related to the dose of ATD. In some patients,
      agranulocytosis developed abruptly, and even weekly routine WBC and granulocyte
      counts failed to predict all case occurrences. Fever and sore throat were the
      earliest symptoms of agranulocytosis; patients who developed either of these
      symptoms were closely monitored immediately with WBC and granulocyte count
      examinations. In this series of patients, treatment with granulocyte-macrophage
      colony stimulating factor (GM-CSF) increased the granulocyte counts, whereas the
      effectiveness of glucocorticoid treatment was not confirmed.

PMID- 12008748
TI  - Twenty-four hour 17-hydroxyprogesterone response to adrenocorticotropine in
      adrenal incidentalomas: augmented response after adrenalectomy in two patients.
AB  - The current study aimed to investigate the midterm (24 hour) response of 17
      hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulphate (DHEA-S) to
      synthetic high-dose adrenocorticotropin (ACTH) in adrenal incidentalomas (Al).
      Seventeen patients with Al and 40 age- and sex-matched controls received
      synthetic ACTH (tetracosactide, 1000 microg, IM). Plasma, 17-OHP and DHEA-S were
      collected in basal conditions and after 1, 4, 6, 8 and 24 hours. (HPA) axis was
      also evaluated using circadian serum cortisol, urinary free cortisol and over
      night 2 mg dexamethasone suppression. Basal plasma 17-OHP levels did not differ
      among the groups. However, the increment in plasma 17-OHP in patients both in
      terms of peak [13.76 +/- 2.52, 4.77 +/- 0.30ng/ml, mean +/- S.E.M, p < 0.001] and
      area under the curve [190 +/- 46, 96.75 +/- 32 ng/ml/h, p < 0.001] were
      significantly higher than that of the controls. Stimulated 17OH-P levels never
      reached 9.1 ng/ml in controls. Sixty-five (11/17) % of the patients were found to
      have exaggerated response. Three of the patients were found to have subclinical
      Cushing's syndrome and interestingly, two augmented their 17-OHP response to ACTH
      after unilateral adrenalectomy and normalisation of their HPA axis. Basal DHEA-S
      levels of the patients were significantly lower [99.21 +/- 45, 230.18 +/- 34
      microg/dl, p < 0.01] and stayed persistently lower than that of the controls.
      Evidence of a heterozygous 21 hydroxylase deficiency, as indicated by the
      exaggerated 17-OHP response to ACTH, has been widely reported in Al patients.
      However, to our knowledge to date there is no report on augmented 17-OHP response
      to ACTH after adrenalectomy. Possible reasons for the augmentation were
      discussed.

PMID- 12008749
TI  - A case of macroprolactinoma with subclinical growth hormone production.
AB  - We describe a rare case of macroprolactinoma with subclinically synchronous
      growth hormone (GH) production. A 59-year-old man with a giant adenoma in his
      pituitary had elevated serum prolactin (PRL) and insulin-like growth factor (IGF)
      I levels, despite normal levels of basal GH. Serum GH levels were paradoxically
      increased in response to an intravenous administration of thyrotropin-releasing
      hormone (TRH). Prolonged exposure to glucose as a result of oral glucose
      tolerance testing (oGTT) failed to decrease GH levels. Two-week treatment with
      cabergoline, a dopamine D2 receptor agonist, decreased serum PRL and GH levels,
      and size of the tumor. Immunohistochemistry and in situ hybridization revealed
      PRL-producing cells capable of synchronous GH production. Acidophilic stem cell
      adenoma may be responsible for these phenomena. The nature of high proliferation
      and invasive tumor growth should be kept in mind when managing patients with this
      cell type of adenoma. IGF-I levels should be followed in PRLoma, even when basal
      GH levels are within the normal range, because mixed PRL- and GH-producing tumors
      would lie underneath. Further endocrinological examinations such as TRH test and
      oGTT are recommended when elevated IGF-I levels are detected.

PMID- 12008750
TI  - Analysis of the AAAS gene in a Japanese patient with triple A syndrome.
AB  - Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive
      disorder characterized by adrenal insufficiency, achalasia and alacrima. It has
      recently been reported that this syndrome is caused by mutations in the AAAS
      gene. In the present study, we analyzed the AAAS gene in a Japanese patient with
      triple A syndrome. The patient was a Japanese girl previously reported by Hirose
      et al. (J Jpn Pediatr Soc 102: 912-915, 1998). The parents of the patient were
      first cousins. The patient was confirmed to have alacrima and isolated
      glucocorticoid deficiency at the age of 2 years. She later developed achalasia of
      the cardia, and was diagnosed as having triple A syndrome. The AAAS gene was
      amplified by the PCR method, and the PCR products were directly sequenced. The
      patient was homozygous for a novel nonsense mutation Q237X, changing codon 237
      encoding Gln (CAA) to a stop codon (TAA). The parents were heterozygous for the
      Q237X mutation. The AAAS gene encodes a protein of 546 amino acids, ALADIN. The
      Q237X mutation is predicted to result in a truncated and presumably non
      functioning ALADIN protein, thus causing the clinically manifest syndrome in the
      patient. To our knowledge, this is the first report on AAAS gene mutations in
      Japan.

PMID- 12008751
TI  - Quantitative estimation and clinical significance of accumulation and washout of
      thallium-201 chloride in follicular thyroid neoplasm.
AB  - PURPOSE: Uptake and washout ratios of thallium-201 chloride (201TlCl) were
      studied to confirm their clinical applicability in the differential diagnosis of
      benign and malignant follicular lesions of the thyroid. PATIENTS AND METHODS:
      Sixty-six patients with follicular tumor of the thyroid underwent preoperative
      thallium scintigram after an intravenous injection of 2 mCi (74 MBq) of 201TlC1.
      The early accumulation and washout ratios of 201TlCl were obtained by an online
      data-processing system. All tumors were surgically resected and
      histopathologically diagnosed as either follicular adenoma (49 patients) or
      follicular carcinoma (17 patients). Scintigraphic values in terms of the early
      accumulation and washout ratios were compared between follicular adenoma and
      follicular carcinoma. RESULTS AND CONCLUSION: Both the early accumulation and
      washout ratios were significantly higher in follicular carcinoma than in
      follicular adenoma. It was concluded that dynamic studies on accumulation and
      washout rates of 201TlCl might be clinically reliable to differentiate between
      follicular adenoma and follicular carcinoma.

PMID- 12008752
TI  - Expression of PGP9.5 in ductal cells of the rat pancreas during development and
      regeneration: can it be a marker for pancreatic progenitor cells?
AB  - The expression of protein gene product 9.5 (PGP9.5), a known neuron marker, was
      immunohistochemically investigated in rat pancreas. In fetal pancreas, a cluster
      of cells expressed PGP9.5 among the initial epithelial buds at embryonic day 11.5
      (E 11.5). At E 13.5, PGP9.5 appeared among elongated and branching epithelial
      cells as well as along nerve fibers in the mesenchyme. On E 17.5, tubular cells
      became ductal cells with lumen, which strongly expressed PGP9.5. In newborn rats,
      ductal cells of the common bile duct (CBD) to the centroacinar cells and islet
      cells expressed PGP9.5. Ten days after birth, the number of the ductal cells
      expressing PGP9.5 was reduced, and PGP9.5-negative cells appeared in half of the
      duct cells. On day 21, all centroacinar cells and intercalated ductal cells
      became PGP9.5-negative, but some CBD and interlobular ductal cells remained
      positive for PGP9.5. On day 28 and thereafter, PGP9.5 was no longer detected. In
      a pancreatic duct ligation model, acinar cells changed to cells with duct-like
      structure after duct ligation. These cells strongly expressed PGP9.5 on the fifth
      day after duct ligation. Three to four weeks after ligation, the cells with duct
      like structure changed to acinar cells, islets of Langerhans and ductal cells,
      but the ductal cells were PGP9.5-negative at this point. These results suggested
      that PGP9.5 is expressed in ductal cells that possess a potential for
      differentiation to pancreatic endocrine cells, and therefore can serve as a
      marker for the progenitor of pancreatic endocrine cells.

PMID- 12008753
TI  - Castration induces apoptosis in the mouse epididymis during postnatal
      development.
AB  - The effect of castration on apoptosis in the mouse epididymis during postnatal
      development was examined. The weight of the epididymis slowly increased from day
      0 (day of birth) to day 20 after birth, followed by a rapid increase thereafter.
      Castration on days 0, 5, 10, 20, 30, 40 and 60 increased apoptotic indices
      (percentages of apoptotic cells) of epithelia of the caput (head), corpus (body),
      and cauda (tail) epididymis, their apoptotic indices reaching maximal levels on
      day 2 after castration with the exception of a maximal apoptotic index on day 4
      in the tail after castration on day 60. The maximal levels of apoptotic indices
      of the head, body and tail after castration on days 0, 5, 10 and 20 were
      significantly lower than those after castration on days 40 and 60. DNAs extracted
      from the epididymides 2 days after castration on days 0, 5, 10 and 60 showed a
      ladder pattern on agarose gel electrophoresis, which is a characteristic of
      apoptosis. When testosterone propionate (10 microg/g body weight) was injected
      twice a day into mice which had been castrated on day 10, 30 or 60, the increases
      in apoptotic indices of the head, body and tail of the epididymis were completely
      inhibited. The weights of the paired epididymides 6 days after castration on days
      0, 5, 10, 20, 30, 40 and 60 were significantly lower than those of sham-operated
      mice, indicating the secretion of androgen by the testes from birth to adulthood.
      The present results indicated that androgen deprivation caused by castration
      induces apoptosis in the epithelium of the epididymis of mice from birth to
      adulthood, and suggested that a proportion of epithelial cells, the survival of
      which is dependent on the testes, is smaller in the epididymides during a slow
      growth stage than in the epididymides after this stage.

PMID- 12008754
TI  - Low serum testosterone level predicts worse response to endocrine therapy in
      Japanese patients with metastatic prostate cancer.
AB  - Patients with prostate cancer generally respond to androgen withdrawal therapy,
      but progression to androgen-independence is frequently observed later. To examine
      whether pretreatment serum androgen status could predict disease progression in
      metastatic prostate cancer, pretreatment serum testosterone, histological grade,
      extent of bony metastasis, serum prostate-specific antigen (PSA) response to
      hormone therapy, and prognosis of the 40 patients with untreated metastatic
      prostate cancer who received endocrine therapy were evaluated. Although there
      were no differences in age, pretreatment PSA level, extent of bony disease and
      histological grade between patients with normal testosterone and those with low
      testosterone, PSA response after endocrine therapy was better in normal
      testosterone group. There was a significantly longer interval to disease
      progression in patients with normal testosterone than in those with low
      testosterone. The patients with metastatic prostate cancer with low serum
      testosterone were in the high risk group of worse response to endocrine therapy.
      Additional therapy might be considered in those patients.

PMID- 12008755
TI  - Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two
      sporadic Japanese patients with Gitelman syndrome.
AB  - Gitelman syndrome is a renal disorder characterized by hypokalemia,
      hypomagnesemia, metabolic alkalosis and hypocalciuria due to the defective
      tubular reabsorption of magnesium and potassium. This disease is caused by
      mutations of thiazide-sensitive Na-Cl cotransporter (TSC) gene. Gitelman syndrome
      is usually distinguished from Bartter syndrome by the presence of both
      hypomagnesemia and hypocalciuria. However, a phenotypic overlap is sometimes
      observed. We encountered two sporadic Japanese patients with Gitelman syndrome
      and analyzed their TSC gene. These patients were diagnosed as Gitelman syndrome
      by the typical clinical findings and biochemical abnormalities, such as mild
      muscular weakness, periodic paralysis, tetany, metabolic alkalosis,
      hypomagnesemia and hypocalciuria. In patient 1, a novel two base deletion (del TG
      at nucleotide 731 and 732) in exon 5 and a two base deletion (del TT at
      nucleotide 2543 and 2544) in exon 21 previously reported in a Japanese patient
      were identified. The patient 2 had a missense mutation (L623P), that was also
      identified in Japanese patients, and a novel in-frame 18 base insertion in exon 6
      as a heterozygous state. Family analysis of two patients confirmed an autosomal
      recessive inheritance. In conclusion, we add two new mutations of the TSC gene in
      Japanese patients with Gitelman syndrome. Because the differential diagnosis
      between Bartter syndrome and Gitelman syndrome is sometimes difficult, molecular
      analysis would be a useful diagnostic tool, particularly in unusual cases with
      phenotypic overlapping.

PMID- 12008756
TI  - The pitfalls of laparoscopic surgery: challenges for robotics and telerobotic
      surgery.
AB  - After its debut in 1988, laparoscopic cholecystectomy rapidly became the standard
      of care for cholelithiasis, yet very few surgeons use minimally invasive
      techniques for other abdominal operations. Why do most surgeons continue to
      perform traditional open gastrointestinal operations? We believe that the answer
      to this question lies in the fact that advanced laparoscopic operations are
      difficult to learn, perform, and master. A number of inherent pitfalls of
      laparoscopy hinder the performance of these operations even after the surgeon has
      accumulated years of experience. These pitfalls include an unstable video camera
      platform, limited motion (degrees of freedom) of straight laparoscopic
      instruments, two-dimensional imaging, and poor ergonomics for the surgeon.
      Inexperienced or bored laparoscopic camera-holders move the camera frequently and
      rotate it away from the horizon. The long, straight laparoscopic instruments are
      limited in their motion by the fixation enforced by the abdominal wall trocars.
      Similarly, the standard two-dimensional video imaging used in most laparoscopic
      operations impedes the surgeon's depth perception, compounding the limitations of
      laparoscopic instruments. In addition, surgeons are forced to assume
      ergonomically awkward stances in performing many laparoscopic operations. These
      four factors hinder a surgeon's efforts to learn and to perform advanced
      laparoscopic operations, significantly lengthening the learning curve. The
      articles presented in this issue suggest that robotics and telerobotics offer
      solutions to these nagging pitfalls of laparoscopic surgery.

PMID- 12008757
TI  - Granting clinical privileges for telerobotic surgery.
AB  - Surgeons can now perform operations on their patients while sitting at a remote
      site. During telerobotic operations, the surgeon sits at a computer console. The
      computer translates the motions of the surgeon's hands into motions of the
      robotic instruments. Introduction of telerobotics into clinical practice raises
      issues comparable to those generated by the rapid introduction of laparoscopic
      cholecystectomy in the late 1980s. As a result, we have instituted processes in
      our hospitals for the granting of clinical privileges for telerobotic surgery.
      These processes are derived from the guidelines of the Society of American
      Gastrointestinal Endoscopic Surgeons for granting clinical privileges for
      laparoscopic general surgery. Our hospitals require the following: (1) board
      certification or board eligibility for the appropriate surgical board; (2)
      clinical privileges for the open and laparoscopic operations that will be
      performed telerobotically; (3) satisfactory completion of the Food and Drug
      Administration-mandated training course in the safe use of the robotic surgical
      system; (4) performance of telerobotic operations in animate models; (5)
      observation of clinical cases of telerobotic surgery by an expert surgeon; (6)
      acting as bedside assistant surgeon in telerobotic operations or supervision by a
      preceptor during the surgeon's initial operations; (7) observation by a proctor
      of the surgeon's initial clinical telerobotic operations; and (8) ongoing
      monitoring of surgical outcomes of telerobotic operations. This process has
      facilitated the safe and orderly introduction of telerobotics operations into
      clinical practice in our hospitals.

PMID- 12008758
TI  - Computer-assisted robotic antireflux surgery.
AB  - Antireflux surgery has evolved significantly since its inception 50 years ago.
      The current standard is laparoscopic fundoplication. The computer-assisted
      telemanipulator, a new device recently approved for use in laparoscopy, reduces
      some of the shortcomings of the laparoscopic approach. This review specifically
      discusses the role of this novel surgical tool in antireflux surgery.

PMID- 12008759
TI  - Robot-assisted laparoscopic Heller's cardiomyotomy.
AB  - There are many options available for the management of achalasia. Recently, the
      list of options has expanded to include robotic-assisted Heller's cardiomyotomy.
      In this article, we describe the procedure for a robotic-assisted cardiomyotomy
      and discuss the advantages of using a robotic, master-slave system.

PMID- 12008760
TI  - Early experience with telemanipulative robot-assisted laparoscopic
      cholecystectomy using da Vinci.
AB  - In the past decade, robot-assisted surgery has become increasingly used to assist
      in minimally invasive surgical procedures. In this article we review the
      evolution of robotic devices, from the first use of an industrial robot for
      stereotactic biopsies to pioneering work with robots used for hip and prostate
      surgery, to the development of robotic guidance systems that enabled solo
      endoscopic surgery, to telemanipulative surgery with master-servant computer
      enhanced robotic devices. In addition, we review our early experience with da
      Vinci Robotic Surgical Systems (Intuitive Surgical, Inc., Mountain View, CA,
      U.S.A.), which we used to perform robot-assisted laparoscopic cholecystectomies.

PMID- 12008761
TI  - Feasibility of robot-assisted laparoscopic surgery: an evaluation of 35 robot
      assisted laparoscopic cholecystectomies.
AB  - Laparoscopic surgery offers patients distinct benefits but is not without its
      disadvantages to surgeons in terms of maneuverability and visualization. Robotic
      telemanipulation systems were introduced with the objective of providing a
      solution to the problems in this field of surgery. The feasibility of robot
      assisted surgery was assessed by performing 35 laparoscopic cholecystectomies
      with the da Vinci robotic system. Time necessary for system setup and operation
      was recorded, as were complications, technical problems, postoperative hospital
      stay, morbidity, and mortality. Thirty-four of 35 cholecystectomy procedures were
      completed laparoscopically with the da Vinci system. Technical problems occurred
      in three cases, resulting in one intraoperative complication (a minilaparotomy
      caused by the loss of an instrument part). Median hospitalization was 2 days.
      There were no postoperative deaths or morbidity within 30 days after surgery.
      System setup time decreased as the experience of the operating team increased.
      Operating times were comparable with those reported for standard laparoscopic
      cholecystectomy. Robot-assisted surgery was repeatedly proven as a safe and
      feasible approach to laparoscopic cholecystectomy.

PMID- 12008762
TI  - Comparison of laparoscopic colectomy with and without the aid of a robotic camera
      holder.
AB  - The use of a robotic camera holder (AESOP 3000; Computer Motion, Inc., Santa
      Barbara, CA, U.S.A.) during laparoscopic surgery is slowly becoming more popular
      with laparoscopic surgeons. However, few published reports document the effects
      of the robot on operative outcomes or operative times. In the current study, we
      compared the use of a voice-controlled robotic camera holder to a human camera
      holder in a series of laparoscopic colectomies. The outcome data measured
      included the number of patients with postoperative complications, the patients'
      length of stay at the hospital, and the operative times for the procedures. There
      were 2 complications among the 11 patients in group 1 (colectomies performed
      without a robotic camera holder), versus 2 complications among the 15 patients in
      group 2 (colectomies performed with a robotic camera holder) (P = NS). Patients
      in group 1 had an average length of stay of 4.1 days, versus 4.4 days for those
      in group 2 (P = NS). The operative time for group 1 was 235 minutes, compared
      with 213 minutes for group 2 (P = NS). The use of a voice-controlled robotic
      camera holder does not alter the length of the operative procedure, the patient's
      length of stay, or postoperative morbidity. However, surgeons often have a
      subjective sense that there is less smudging, fogging, and inadvertent movements
      of the laparoscope when it is controlled by a robotic system. In addition, using
      a voice-controlled robot as a camera holder does eliminate the need for a
      surgical assistant.

PMID- 12008763
TI  - Early experience with robotically assisted internal thoracic artery harvest.
AB  - We sought to determine the efficacy of using robotic assistance to facilitate
      endoscopic harvesting of internal thoracic arteries (ITAs). A total of 104
      patients had ITAs harvested endoscopically with use of both the AESOP 3000 system
      (Computer Motion, Goleta, CA, U.S.A.) and Zeus robotic telesurgical system
      (Computer Motion). All ITAs were harvested with a harmonic scalpel (Ethicon
      Endosurgery, Cincinnati, OH, U.S.A.). With the left lung collapsed, ITAs were
      harvested with CO2 insufflation through three 5-mm ports in the left chest. All
      patients tolerated insufflation without hemodynamic compromise. Average ITA
      harvest time was 61.3 +/- 20.9 minutes. Intraoperative graft flows averaged 36.3
      +/- 22.4 mL/min. There were three distal ITA injuries; all other vessels were
      patent after harvesting and demonstrated no angiographic evidence of injury. This
      article demonstrates a technique by which ITA can be safely harvested totally
      endoscopically with use of computer-enhanced robotic systems and a harmonic
      scalpel, allowing complete pedicle dissection through 5-mm ports with minimal ITA
      manipulation.

PMID- 12008764
TI  - The evolution of and early experience with robot-assisted mitral valve surgery.
AB  - Cardiac surgeons have embraced minimally invasive surgery with warranted
      enthusiasm. The acceleration of technological advances in optics,
      instrumentation, and cardiopulmonary bypass has allowed safe, effective,
      efficient minimally invasive cardiac procedures. In this article we review the
      evolution of and early experience with robot-assisted mitral valve surgery.
      Articles by leaders in the field of minimally invasive cardiac surgery, both
      American and European, are reviewed to describe the development of cardiac
      robotic surgery. The current state of robotic mitral surgery is described.

PMID- 12008765
TI  - Surgical robotics: the early chronicles: a personal historical perspective.
AB  - The use of robotics has been emerging for approximately 75 years, but only during
      the past 5 years has the potential of robotics been recognized by the surgical
      community as a whole. This personal perspective chronicles the development of
      robotics for the general surgical community, the role of the military medical
      research effort, and many of the major programs that contributed to the current
      success of robotics.

PMID- 12008766
TI  - Early experience with robotically assisted laparoscopic donor nephrectomy.
AB  - The da Vinci robotic system became available at our institution in late August
      2000. We decided to use this system to perform robotically assisted laparoscopic
      donor nephrectomies. A prospective study was conducted of 10 consecutive patients
      who underwent robotically assisted laparoscopic donor nephrectomy between January
      and May 2001. The mean operative time was 166 minutes. The mean hospital stay was
      1.8 days. The need for parenteral pain medication was limited to the first
      postoperative day. All kidneys were transplanted successfully; no rejections
      occurred. This early experience suggests that the results of robotically assisted
      laparoscopic donor nephrectomy are similar to those of laparoscopic donor
      nephrectomy. We believe that robotic surgery, which enables regaining of the hand
      eye coordination and three-dimensional view lost in laparoscopic surgery, allows
      us to perform the donor nephrectomy with greater precision, confidence, and
      comfort.

PMID- 12008767
TI  - Applications of robotic surgery in pediatric patients.
AB  - Minimally invasive surgery is increasingly becoming the standard approach to
      treatment for pediatric patients. Infants present a technical challenge due to
      the small size of structures and the small workspace available. Master-slave
      robotic surgical telemanipulators help overcome this challenge by facilitating
      microsurgery in a confined workspace. The Zeus Robotic Surgical System (Computer
      Motion, Inc., Goleta, CA, U.S.A.) was used to develop the robotic approach and to
      evaluate the technical feasibility of performing four technically challenging
      procedures that are typically performed in infants. Robotic enteroenterostomy,
      hepaticojejunostomy, portoenterostomy, and esophagoesophagostomy were performed
      in piglets and compared with the same procedures performed by standard minimally
      invasive techniques. Enteroenterostomy, hepaticojejunostomy, and
      esophagoesophagostomy procedures were successfully developed and are technically
      feasible. The portoenterostomy procedure needs further study to validate data
      from the second set of experiments, showing a lower complication rate in the
      robotic group. Survivor studies are needed to fully elucidate the advantages that
      may be provided by the robotic approach.

PMID- 12008768
TI  - Hippocrates: father of medicine.

PMID- 12008769
TI  - Testing the Bolam Test: consequences of recent developments.

PMID- 12008770
TI  - Malaysian children with spina bifida: relationship between functional outcome and
      level of lesion.
AB  - PURPOSE: To determine the relationship between spinal lesion level and functional
      outcome in children with spina bifida. METHODS: Prospective observational study
      of 66 children who attended the Spina Bifida Clinic from 1994-1997. Data were
      obtained from serial physical examination and parent interview to determine
      mobility status, neurosensory deficits, continence and school placement. RESULTS:
      Eighteen (27.3%) had high-level (thoracic and thoracolumbar), 27 (40.9%)
      intermediate (low lumbar) and 21 (31.8%) low-level (sacral) lesions. Children
      with high-level lesions experienced more mobility problems (independent
      ambulation, balance and use of appliances), than those with intermediate or low
      level lesions (p<0.001). 58.8% of children with low-level lesions used diapers,
      compared with those with high (90%) or intermediate (100%) level lesions (p =
      0.005), but there were no significant differences in the incidence of soiling or
      urinary incontinence among all three groups. There were no significant
      differences among the three groups in terms of school placement, skin breakdown,
      epilepsy or visual defect. CONCLUSION: Although there is good correlation between
      the level of the lesion and mobility in children with spina bifida, other
      measures of functional outcome like continence and school placement are more
      difficult to predict. These data are important for realistic counselling of
      families with newborns with spina and planning long term rehabilitation
      resources.

PMID- 12008771
TI  - Health promotion programme in the private workplaces in Singapore: a prevalence
      survey.
AB  - A postal survey was conducted in 4,479 private companies with at least 50
      employees in 1998 to determine the prevalence and the scope of workplace health
      promotion programme in these companies in Singapore. The self-administered
      questionnaire mailed to the study population covered five areas viz,
      organisational details, workplace health policies, health promotion and related
      activities, workplace health facilities and the source of assistance for the
      programme. The overall response was 49.5%. Parkinson's definition of workplace
      health promotion was used in the analysis to determine the prevalence of the
      programme. The data was collated on DBase IV and analysed using SPSS computer
      programmes. About one third of the respondents covering an estimated 26% of the
      private sector workforce had a comprehensive workplace health promotion programme
      as defined by Parkinson. This prevalence was a function of workforce size and
      industry type. Workplaces with larger workforce size (p<0.001) and those from the
      manufacturing and human/health service sectors (p<0.001) were more likely to have
      such programmes compared to their smaller counterparts and other industries
      respectively. The management remained the main driver behind these programmes.
      Many of the programmes were centred around health promoting policies and
      facilities with emphasis on occupational healthl safety and smoking issues. A
      significant proportion of workplaces surveyed had in place a comprehensive
      workplace health promotion programme. However, more could still be done to
      encourage its uptake such as training for facilitators, consultation, grant
      provision etc. Small workplaces remained an untapped market for such programmes.

PMID- 12008772
TI  - Massive pulmonary embolism with haemodynamic collapse.
AB  - Massive pulmonary embolism with shock remains a highly fatal disease. We present
      twelve cases of massive embolism over the last seven years that required emergent
      surgery. Five patients suffered haemodynamic collapse and all died despite heroic
      attempts at salvage. A better outcome can only be achieved in this sub-category
      of patients with a rapid confirmatory diagnosis and appropriate thrombolysis and
      early referral to a cardiothoracic surgeon.

PMID- 12008773
TI  - Laser skin resurfacing treatment outcome of facial scars and wrinkles in Asians
      with skin type III/IV with the Unipulse CO2 laser system.
AB  - OBJECTIVE: To study the efficacy and complications from Unipulse CO2 laser
      resurfacing system (Nidek, California) for the treatment of scars and wrinkles in
      patients with Type III and IV skin type. METHODOLOGY: This is a prospective study
      of patients with skin type III and IV who received laser-resurfacing treatment
      for facial scars and wrinkles. All patients received topical tretinoin 0.025%
      cream at least two weeks prior to laser resurfacing. Laser resurfacing was
      carried out under lidocaine 1% nerve blocks with the Unipulse CO2 laser scanning
      system. The power at tissue was set at 15 watts (fluence = 6.12 J/cm2; spot size
      = 1.02 mm, frequency = 300 Hz), with a 20% overlap. Lesions around the eyes were
      resurfaced with one pass. Those on other parts of the face with two to three
      passes. Patients were assessed up to 12 months. Treatment response (assessed by
      patient and dermatologist) was graded as "no change" = no improvement, "minimal
      improvement" = <25% clearance, "moderate improvement" = 25-50% clearance,"good
      improvement" = 50-75% clearance and "excellent improvement" = >75% clearance.
      Complications (assessed by dermatologist only) including erythema,
      hypopigmentation and hyperpigmentation were scored subjectively as none, minimal,
      mild, moderate and severe. RESULTS: 16 (nine females, seven males) patients were
      studied. Thirteen patients were treated for acne scars, two patients for wrinkles
      and one patient for chicken pox scar. Their mean age was 30.7 years (SD = 9.5
      years). Fifteen patients had skin type IV and I had skin type III. TREATMENT
      RESPONSE: Thirteen patients were assessed at six weeks post laser treatment. One
      (8%) patient had "minimal improvement" (<25%) improvement, 10 (77%) patients had
      "moderate improvement" (25-50%) and 2 (15%) patients had "moderate improvement"
      (50-75%) improvement. At six months, 37% had "minimal improvement", 37% had
      "moderate improvement" and two had "good improvement and one patient with fine
      wrinkles had "excellent improvement". COMPLICATIONS: All patients experienced
      severe erythema at Day 1. Erythema faded over six months. By three months only
      22% had minimal erythema and by six months none had erythema. Moderate
      pigmentation developed in 15% at six weeks. At three months 33% had varying
      degree of pigmentation. At six months one (12%) patient had residual
      pigmentation. Only one patient developed mild minimal hypopigmentation at six
      month, which cleared at 12 months. Another patient developed hypopigmentation at
      12 months. CONCLUSION: CO2 laser resurfacing provides minimal to moderate
      improvements for scars and wrinkles among Asians with darker skin type. Erythema
      fades over six months after resurfacing. Post-inflammatory pigmentation is common
      but tends to clear over six months.

PMID- 12008774
TI  - Is increasing age associated with mortality in the critically ill elderly.
AB  - INTRODUCTION: Age has been cited as a predictor of mortality in the intensive
      care unit (ICU) and suggested as a criterion for rationing resources. We
      investigated the association of age with both ICU mortality and hospital
      mortality. MATERIALS AND METHODS: Patients admitted in 1998 to our Medical ICU
      (MICU) were retrospectively analysed by stratifying them into four groups: the
      reference group (55-64 years), the young old (65-74 years), the old old (75-84
      years) and the oldest old (more than 85 years). The statistical association of
      age with ICU mortality and total hospital mortality was determined whilst
      controlling for the APACHE II(M) score (APACHE II score modified to exclude
      points for age), the number of organ failures and the presence of a high risk
      admitting diagnosis. RESULTS: After controlling for disease severity, the ICU
      mortality and the total hospital mortality were not associated with age. The
      total hospital mortality was associated with the APACHE II(M) score (Odds ratio
      (OR), 1.08; 95% Confidence intervals (CI), 1.04-1.12), the number of organ
      failures (OR, 2.03; CI, 1.50-2.67) and the presence of a high risk diagnosis (OR,
      3.50; CI 1.93-6.37). The ICU mortality was also associated with the APACHE II(M)
      score (OR, 1.07; CI, 1.03-1.11), the number of organ failures (OR, 1.63; CI, 1.26
      2.09) and the presence of a high risk diagnosis (OR, 3.22; CI 1.81-5.76).
      CONCLUSIONS: We did not find a statistically significant association between age
      and mortality. We recommend that age should not be used as a criterion for
      admission.

PMID- 12008775
TI  - Gastric carcinoma presenting with cellulitis-like cutaneous metastasis.
AB  - INTRODUCTION: A case of carcinoma of the stomach presenting with cellulitis-like
      cutaneous metastasis is reported. CLINICAL PICTURE: This patient was diagnosed to
      have early stage carcinoma of the prostate (T1bN0M0), which was treated with
      radiotherapy and hormonal therapy. He presented with an erythematous area of
      induration over the right neck a few weeks after the completion of radical
      radiotherapy. The CT scan of the neck showed features suggestive of cellulitis of
      the right cervical region. Due to the lack of response to intravenous
      antibiotics, a fine needle aspiration biopsy of the indurated area was done. This
      confirmed the presence of adenocarcinoma. Due to the presence of iron-deficiency
      anaemia and the positive occult blood test in the stool, an upper
      gastrointestinal endoscopy was done. This confirmed the presence of
      adenocarcinoma of the stomach of the signet-ring cell type. OUTCOME: He had a
      rapid downhill course after the diagnosis and died four weeks after the diagnosis
      was made. CONCLUSION: Carcinoma of the stomach can rarely present with cutaneous
      metastasis as a cellulitis-like picture.

PMID- 12008776
TI  - Carcinoma of the rectum with a single penile metastasis.
AB  - Metastatic disease of colon and rectal carcinoma accounts for a high proportion
      of cancer related deaths. The common organs involved in metastatic diseases
      include liver, lung, brain and bone. Although, theoretically possible, metastasis
      to the other organs are rare. We report the first case of carcinoma of the rectum
      with a solitary metastasis to the glans penis.

PMID- 12008777
TI  - Hormone replacement therapy (HRT) and ischaemic heart disease: getting to the
      heart of the matter.
AB  - Numerous observational studies have previously shown that estrogen therapy (ERT)
      or estrogen/progestin hormone replacement therapy (HRT) can significantly reduce
      the risk of Coronary Artery Disease (CAD) in healthy postmenopausal women by up
      to 50%. However, due to statistical limitations inherent in these earlier
      studies, several large randomised trials are now under way. The results from some
      of these randomised trials are expected sometime in 2005 and will certainly help
      confirm or refute the present perceived cardio-protective effects of ERT/HRT in
      healthy menopausal women. On the other hand, the role of hormonal therapy in
      menopausal women with established CAD is more controversial. Although results
      from earlier observational trials have been encouraging, more recent randomised
      controlled data from the Heart and Estrogen/Progestin Replacement (HER) study and
      the Estrogen Replacement and Atherosclerosis (ERA) study have been more sober. In
      fact, both have generally reported on the failure of ERT/HRT to reduce the
      overall rate of ischaemic cardiovascular events or to halt the progression of
      coronary atherosclerosis in menopausal women with established CAD. However, these
      studies are not without their own limitations. As such, more future trials will
      be needed before the role of postmenopausal hormone therapy in the secondary
      prevention of CAD can be firmly established.

PMID- 12008778
TI  - Article: Understanding traditional Chinese medicine--a doctor's viewpoint (N K
      Ho).

PMID- 12008779
TI  - Article: Characteristics of patients referred to an insomnia clinic (R
      Mahendran).

PMID- 12008780
TI  - Article: Paradoxical enlargement of tuberculous brain abscess during drug
      treatment: a case report (S K Ng, et al).

PMID- 12008781
TI  - Clinics in diagnostic imaging (69). Bilateral developmental dysplasia of the hip.
AB  - Developmental dysplasia of the hip (DDH) is a condition encompassing a spectrum
      of abnormality. The ultrasonography features of DDH in a male infant is
      illustrated. Follow-up after treatment with a Pavlik harness shows resolution of
      the DDH. In the neonatal period, ultrasonography (US) is the modality of choice
      used to evaluate babies with suspected developmental dysplasia of the hip. The
      unossified cartilaginous femoral head and much of the acetabulum can be
      visualised on US. When the femoral head begins to ossify, pelvic radiographs can
      be used to follow-up patients with developmental dysplasia of the hips.

PMID- 12008782
TI  - Therapy for recurrent respiratory papillomatosis.
AB  - Human papillomaviruses types 6 or 11 are aetiological agents of recurrent
      respiratory papillomatosis, a disease characterized by benign exophytic tumours
      usually on the vocal cords. Surgery debulks the tumours, but these growths
      generally recur at regular intervals. Adjunct medical treatments, aimed at
      containing the virus and growth of tumours, include indole-3-carbinol or its
      dimer diindolylmethane, interferon, photodynamic therapy and others. Preventive
      and therapeutic vaccines hold promise for eliminating the virus.

PMID- 12008783
TI  - Observations of HIV-1 genotypic drug resistance in a trial of four reverse
      transcriptase inhibitors (Quattro Trial).
AB  - The Quattro Trial compared the use of four HIV-1 reverse transcriptase (RT)
      inhibitors (zidovudine, lamivudine, loviride and zalcitabine), given either as
      four-drug combination therapy or monotherapy, with 8-week cycles of each drug,
      with zidovudine/lamivudine dual therapy. Observations of resistance associated
      and other mutations in the RT gene were made to determine whether therapy failure
      could be explained by acquisition of these mutations and whether novel mutation
      patterns developed. As in the intent-to-treat analysis, the use of cyclical
      monotherapy gave a smaller reduction in plasma virus load at 64 weeks (0.4 log10
      copies/ml below baseline) than the quadruple or dual therapy arms (1.3 and 0.8
      log10 copies/ml below baseline). Cyclical therapy appeared to generate less
      genotypic resistance to zidovudine, loviride or zalcitabine than the other arms.
      Resistance to lamivudine (mutation M184V) developed rapidly in all three arms.
      Resistance to zidovudine was acquired by a larger proportion of subjects on dual
      therapy than on quadruple therapy. Resistance to loviride or zalcitabine was
      rarely observed. During lamivudine monotherapy the M184V mutation was rapidly
      acquired and viral load rebounded. Zalcitabine monotherapy initially selected
      M184V mutants, but these were lost as therapy continued. Novel mutations that may
      have been associated with combination or cyclical quadruple therapy were observed
      infrequently. There was no clear correlation between changes in response to
      therapy and the development of previously described resistance mutations or with
      novel mutations in the RT gene.

PMID- 12008784
TI  - Response to antiretroviral therapy among patients exposed to three classes of
      antiretrovirals: results from the EuroSIDA study.
AB  - There is an increasing proportion of HIV-positive patients exposed to all
      licensed classes of antiretrovirals, and the response to salvage regimens may be
      poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients
      exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse
      transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four
      hundred-and-thirteen patients, who had failed virologically two highly active
      antiretroviral therapy (HAART) regimens and experienced all three main drug
      classes, started a salvage regimen of at least three drugs, in which at least one
      new PI or NNRTI was included. Median viral load was 4.7 log copies/ml
      [Interquartile range (IQR) 4.2-5.2], CD4 lymphocyte count 150/mm3 (IQR 60
      274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently
      experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral
      load < 500 copies/ml. Conversely, the CD4 count halved from the baseline value in
      88 (21%), and 45 (11%) experienced a new AIDS-defining disease. In multivariable
      analyses, a 1 log viral load reduction was related to baseline viral load
      [relative hazard (RH) 1.27 per 1 log higher; P = 0.008], a previous viral load of
      less than 500 copies/ml (RH 1.69; P = 0.002), more recent initiation of the
      regimen (RH 1.36 per year more recent; P = 0.02), number of new drugs in the
      regimen (RH 1.20 per drug; P = 0.02), time since start of antiretroviral therapy
      (RH 0.94 per extra year; P = 0.035) and time spent on HAART with viral load >
      1000 copies/ml (RH 0.96 per extra month; P = 0.0001). Analysis of factors
      associated with CD4 count decline and new AIDS disease also indicated improved
      outcomes in more recent times and a tendency for a better response in those
      starting more new drugs, but no relationship with the total number of drugs.
      Outcomes in people starting salvage regimens appear to depend on the number of
      new drugs started but not on the total number of drugs being used.

PMID- 12008785
TI  - Prevalence and response to antiretroviral therapy of non-B subtypes of HIV in
      antiretroviral-naive individuals in British Columbia.
AB  - In North America, the B subtype of the major group (M) of HIV-1 predominates.
      Phylogenetic analysis of HIV reverse transcriptase and protease sequences
      isolated from 479 therapy-naive patients, first seeking treatment in British
      Columbia between June 1997 and August 1998, revealed a prevalence of 4.4% non-B
      virus. A range of different subtypes was identified, including one subtype A, 11
      C, two D, five CRF01_AE, and one sample that could not be reliably subtyped.
      Baseline CD4 courts were significantly lower in individuals harbouring the non-B
      subtypes (P = 0.02), but baseline viral loads were similar (P = 0.80). In this
      study, individuals infected with non-B variants did not have a significantly
      different virological response to therapy after up to 18 months.

PMID- 12008786
TI  - Persistence of viral HLA-DR- CD4 T-cell reservoir during prolonged treatment of
      HIV-1 infection with a five-drug regimen.
AB  - During sustained suppression of plasma viraemia using a standard triple-drug
      regimen, replication-competent HIV-1 can still be recovered from resting memory
      CD4 T cells. In an attempt to accelerate the clearance of this pool of infected
      CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were
      treated with a five-drug regimen. While plasma HIV-1 RNA levels generally
      remained below the level of detection (< 5 copies/ml), replication competent HIV
      1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions
      throughout treatment. Decay slopes of infected CD4 T cells ranged from 
      0.061/week (half-life=2.6 months) to +0.003/week (half-life = infinite). Virus
      was still detectable at the last time point analysed (80-173 weeks) in all
      patients. Although more intensive treatment results in improved suppression of
      plasma viraemia compared with standard drug regimens, it does not result in
      clearance of the viral reservoir in this timeframe. Strategies other than
      treatment with a combination of five of the currently available drugs need to be
      pursued in order to achieve eradication of HIV-1 from this cellular reservoir.

PMID- 12008787
TI  - Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine
      and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy.
AB  - OBJECTIVE: To evaluate HIV-1 reverse transcriptase (RT) drug resistance in
      patients receiving abacavir, lamivudine and zidovudine therapy. METHODS: In a
      randomized, double-blind study, 173 antiretroviral treatment-naive HIV-1-infected
      adults received abacavir/lamivudine/zidovudine or lamivudine/zidovudine for up to
      48 weeks. After week 16, patients could switch to open-label
      abacavir/lamivudine/zidovudine, and those with plasma HIV-1 RNA (vRNA) > 400
      copies/ml could add other antiretrovirals. From weeks 11 to 48, samples with vRNA
      > 400 copies/ml were collected for genotyping and phenotyping. RESULTS: At
      baseline, 90% of isolates were wild-type (WT). At week 16, vRNA was > 400
      copies/ml in seven of 72 (10% patients receiving abacavir/lamivudine/zidovudine
      and in 41 of 66 (62%) receiving lamivudine/ zidovudine. At week 16, the genotypes
      in isolates from the abacavir/lamivudine/zidovudine group were M184V alone (n = 3
      cases), WT (n = 3) and M184V plus thymidine analogue mutations (TAMs) (n = 1).
      The genotypes in isolates from the lamivudine/zidovudine group were M184V alone
      (n = 37), WT ( n= 1) and M184V plus TAMs (n = 3). In the four cases where M184V
      plus TAMs were detected some mutations were present at baseline. Despite
      detectable M184V in 74% of patients on lamivudine/zidovudine, addition of
      abacavir with or without another antiretroviral therapy resulted in a reduction
      in vRNA, with 42 of 65 (65%) patients having week 48 vRNA < 400 copies/ml (intent
      to-treat with missing = failure). At week 48, the most common genotype was M184V
      alone in the abacavir/ lamivudine/zidovudine group (median vRNA 1-2 log,10 below
      baseline), and M184V with or without TAMs in patients originally assigned to
      lamivudine/zidovudine. At week 48, phenotypic results were obtained for 11
      isolates for patients from both arms, and all had reduced susceptibility to
      lamivudine but all remained sensitive to stavudine, all protease inhibitors and
      all non-nucleoside reverse transcriptase inhibitors. Three, three and two
      isolates had reduced susceptibility to abacavir, didanosine and zidovudine,
      respectively. CONCLUSIONS: Abacavir retained efficacy against isolates with the
      M184V genotype alone. TAMs did not develop during 48 weeks of
      abacavir/lamivudine/zidovudine therapy and were uncommon when abacavir was added
      after 16 weeks of lamivudine/zidovudine therapy. Limited mutations upon rebound
      on this triple nucleoside combination allows for several subsequent treatment
      options.

PMID- 12008788
TI  - Oral pleconaril treatment of picornavirus-associated viral respiratory illness in
      adults: efficacy and tolerability in phase II clinical trials.
AB  - We evaluated the efficacy and tolerability of oral pleconaril, an anti
      picornavirus agent, in treating acute viral respiratory illness (VRI) in two
      double-blind, placebo-controlled trials. Otherwise healthy subjects, 14 years of
      age or older, who presented within 36 h of VRI symptom onset, were randomized to
      pleconaril 400 mg or matching placebo in liquid (first trial) or tablet (second
      trial) formulations twice-daily (first trial only) or three-times daily for 7
      days. The infected subjects from the corresponding active and placebo groups
      (three-times daily dosing regimens) were combined for analysis. Among the subset
      of subjects with proven picornaviral infection in both studies (42% of total
      enrolled), pleconaril 400 mg three-times daily (n = 323) reduced the time to
      alleviation of illness (no rhinorrhoea and other symptoms mild or absent for > or
      = 48 h) compared with placebo (n = 264) (median: 10.0 days for placebo and 8.5
      days for pleconaril; P = 0.029). In addition, pleconaril reduced the time to a >
      or = 50% reduction from baseline in total symptom severity score (median: 4.5
      days for placebo and 3.5 days for pleconaril; P = 0.038). Significant reductions
      in the number of tissues used for nose-blowing (20% reduction) and in nights of
      disturbed sleep (16% reduction) were also observed. Pleconaril was generally well
      tolerated; the liquid formulation caused gastrointestinal disturbance in all
      groups (diarrhoea 10-14%, nausea 5-9%, abdominal discomfort 6-8%), and tablets
      were associated with a greater incidence of nausea (3% for placebo versus 7% for
      pleconaril, P = 0.003). Pleconaril 400 mg administered three-times daily reduced
      the duration and severity of picornaviral VRI in adolescents and adults.

PMID- 12008789
TI  - The 19th International Papillomavirus Conference.

PMID- 12008790
TI  - Claims about religious involvement and health outcomes.
AB  - Claims about religion, spirituality, and health have recently appeared with
      increasing frequency, in both the popular media and professional journals. These
      claims have asserted that there are a great many studies in the literature that
      have examined relations between religious involvement and health outcomes and
      that the majority of them have shown that religious people are healthier. We
      examined the validity of these claims in two ways: (a) To determine the
      percentage of articles in the literature that were potentially relevant to such a
      claim, we identified all English-language articles with published abstracts
      identified by a Medline search using the search term religion in the year 2000,
      and (b) to examine the quality of the data in articles cited as providing
      supportfor such a claim, we examined all articles in the area of cardiovascular
      disease and hypertension cited by two comprehensive reviews of the literature. Of
      the 266 articles published in the year 2000 and identified by the Medline search,
      only 17% were relevant to claims of health benefits associated with religious
      involvement. About half of the articles cited in the comprehensive reviews were
      irrelevant to these claims. Of those that actually were relevant, many either had
      significant methodological flaws or were misrepresented, leaving only afew
      articles that could truly be described as demonstrating beneficial effects of
      religious involvement. We conclude that there is little empirical basis for
      assertions that religious involvement or activity is associated with beneficial
      health outcomes.

PMID- 12008791
TI  - The daily spiritual experience scale: development, theoretical description,
      reliability, exploratory factor analysis, and preliminary construct validity
      using health-related data.
AB  - Spirituality and religiousness are gaining increasing attention as health
      research variables. However, the particular aspects examined vary from study to
      study, ranging from church attendance to religious coping to meaning in life.
      This frequently results in a lack of clarity regarding what is being measured,
      the meaning of the relationships between health variables and spirituality, and
      implications for action. This article describes the Daily Spiritual Experience
      Scale (DSES) and its development, reliability, exploratory factor analyses, and
      preliminary construct validity. Normative data from random samples and
      preliminary relationships of health-related data with the DSES also are included.
      Detailed data for the 16-item DSES are provided from two studies; a third study
      provided data on a subset of 6 items, and afourth study was done on the
      interrater reliability of the item subset. A 6-item version was used in the
      General Social Survey because of the need to shorten the measure for the survey.
      A rationale for the conceptual underpinnings and item selection is provided, as
      are suggested pathways for linkages to health and well-being. This scale
      addresses reported ordinary experiences of spirituality such as awe, joy that
      lifts one out of the mundane, and a sense of deep inner peace. Studies using the
      DSES may identify ways in which this element of life may influence emotion,
      cognition and behavior, and health or ways in which this element may be treated
      as an outcome in itself a particular component of well-being. The DSES evidenced
      good reliability across several studies with internal consistency estimates in
      the .90s. Preliminary evidence showed that daily spiritual experience is related
      to decreased total alcohol intake, improved quality of life, and positive
      psychosocial status.

PMID- 12008792
TI  - Spirituality and health: what's the evidence and what's needed?
AB  - In this article, we familiarize readers with some recent empirical evidence about
      possible associations between religious and/or spiritual (RS) factors and health
      outcomes. In considering this evidence, we believe a healthy skepticism is in
      order One needs to remain open to the possibility that RS-related beliefs and
      behaviors may influence health, yet one needs empirical evidence based on well
      controlled studies that support these claims and conclusions. We hope to
      introduce the dismissing critic to suggestive data that may create tempered doubt
      and to introduce the uncritical advocate to issues and concerns that will
      encourage greater modesty in the making of claims and drawing of conclusions. We
      comment on the following questions: Do specific RS factors influence health
      outcomes? What possible mechanisms might explain a relation, if one exists? Are
      there any implications for health professionals at this point in time?
      Recommendations concern the need to improve research designs and measurement
      strategies and to clarify conceptualizations of RSfactors. RSfactors appear to be
      associated with physical and overall health, but the relation appears far more
      complex and modest than some contend. Which specific RS factors enhance or
      endanger health and well-being remains unclear.

PMID- 12008793
TI  - The Ironson-woods Spirituality/Religiousness Index is associated with long
      survival, health behaviors, less distress, and low cortisol in people with
      HIV/AIDS.
AB  - The purpose of this study was to determine the reliability and validity of an
      instrument that measures both spirituality and religiousness, to examine the
      relation between spirituality and religiousness and important health outcomes for
      people living with HIV and to examine the potential mediators of these relations.
      One aim was to determine whether subscales of spirituality, religiousness, or
      both would be independently related to long survival in people living with AIDS.
      The Ironson-Woods Spirituality/Religiousness (SR) Index is presented with
      evidence for its reliability and validity. Four factors were identified on the
      Ironson-Woods SR Index (Sense of Peace, Faith in God, Religious Behavior, and
      Compassionate View of Others). Each subscale was significantly related to long
      survival with AIDS. That is, the long-term survivor (LTS) group (n = 79) scored
      significantly higher on these factors than did the HIV-positive comparison (COMP)
      group (n = 200). Long survival was also significantly related to both frequency
      of prayer (positively) and judgmental attitude (negatively). In addition, the
      Ironson-Woods SR Index yielded strong and significant correlations with less
      distress, more hope, social support, health behaviors, helping others, and lower
      cortisol levels. The relation between religious behavior and health outcomes was
      not due to social support. Further analyses were conducted, which identified
      urinary cortisol concentrations and altruistic behavior as mediators of the
      relation between SR and long survival.

PMID- 12008794
TI  - Measuring spiritual well-being in people with cancer: the functional assessment
      of chronic illness therapy--Spiritual Well-being Scale (FACIT-Sp).
AB  - A significant relation between religion and better health has been demonstrated
      in a variety of healthy and patient populations. In the past several years, there
      has been a focus on the role of spirituality, as distinctfrom religion, in health
      promotion and coping with illness. Despite the growing interest, there remains a
      dearth of well-validated, psychometrically sound instruments to measure aspects
      of spirituality. In this article we report on the development and testing of a
      measure of spiritual well-being, the Functional Assessment of Chronic Illness
      Therapy-Spiritual Well-Being (FACIT-Sp), within two samples of cancer patients.
      The instrument comprises two subscales--one measuring a sense of meaning and
      peace and the other assessing the role offaith in illness. A total score for
      spiritual well-being is also produced. Study 1 demonstrates good internal
      consistency reliability and a significant relation with quality of life in a
      large, multiethnic sample. Study 2 examines convergent validity with 5 other
      measures of religion and spirituality in a sample of individuals with mixed early
      stage and metastatic cancer diagnoses. Results of the two studies demonstrate
      that the FACIT-Sp is a psychometrically sound measure of spiritual well-being for
      people with cancer and other chronic illnesses.

PMID- 12008795
TI  - Correlates of self-perceptions of spirituality in American adults.
AB  - To advance knowledge in the study of spirituality and physical health, we
      examined sociodemographic, behavioral, and attitudinal correlates of self
      perceptions of spirituality. Participants were a nationally representative sample
      of 1,422 adult respondents to the 1998 General Social Survey. They were asked,
      among other things, to rate themselves on the depth of their spirituality and the
      depth of their religiousness. Results indicated that, after adjustment for
      religiousness, self-perceptions of spirituality were positively correlated with
      being female (r = .07, p < .01), having a higher education (r = .12, p < .001),
      and having no religion (r = .10, p < .001) and inversely correlated with age (r =
      -.06, p < .05) and being Catholic (r = -.08, p < .01). After adjustment for these
      sociodemographic factors, self-perceptions of spirituality were associated with
      high levels of religious or spiritual activities (range in correlations = .12
      .38, all p < .001), low cynical mistrust, and low political conservatism (both r
      = -.08, p < .01). The population was divided into 4 groups based on their self
      perceptions of degree of spirituality and degree of religiousness. The spiritual
      and religious group had a higherfrequency of attending services, praying,
      meditating, reading the Bible, and daily spiritual experience than any of the
      other 3 groups (all differences p < .05) and had less distress and less mistrust
      than the religious-only group (p < .05 for both). However, they were also more
      intolerant than either of the nonreligious groups (p < .05 for both) and similar
      on intolerance to the religious-only group. We conclude that
      sociodemographicfactors could confound any observed association between
      spirituality and health and should be controlled. Moreover, individuals who
      perceive themselves to be both spiritual and religious may be at particularly low
      risk for morbidity and mortality based on their good psychological status and
      ongoing restorative activities.

PMID- 12008796
TI  - Should clinicians incorporate positive spirituality into their practices? What
      does the evidence say?
AB  - Most of the rhetoric decrying the incorporation of basic and positive spiritual
      care into clinical practice is not based on reliable evidence. We briefly review
      the current evidence, which demonstrates that (a) there is frequently a positive
      association between positive spirituality and mental and physical health and well
      being, (b) most patients desire to be offered basic spiritual care by their
      clinicians, (c) most patients censure our professions for ignoring their
      spiritual needs, (d) most clinicians believe that spiritual interventions would
      help their patients but have little training in providing basic spiritual
      assessment or care, (e) professional associations and educational institutions
      are beginning to provide learners and clinicians information on how to
      incorporate spirituality and practice, and (j) anecdotal evidence indicates that
      clinicians having received such training find it immediately helpful and do apply
      it to their practice. We point out the reasons that much more research is needed,
      especially outcome-based, clinical research on the effects of these spiritual
      interventions by clinicians. We conclude that the evidence to date demonstrates
      trained or experienced clinicians should encourage positive spirituality with
      their patients and that there is no evidence that such therapy is, in general,
      harmful. Further, unless or until there is evidence of harm from a clinician's
      provision of either basic spiritual care or a spiritually sensitive practice,
      interested clinicians and systems should learn to assess their patients'
      spiritual health and to provide indicated and desired spiritual intervention.
      Clinicians and health care systems should not, without compelling data to the
      contrary, deprive their patients of the spiritual support and comfort on which
      their hope, health, and well-being may hinge.

PMID- 12008797
TI  - The witches' brew of spirituality and medicine.
AB  - Recent proposals to join spirituality and medicine are facile and ill defined.
      The notion that physicians have the time or training to make assessments and
      recommendations about spirituality is misguided. Whenever a physician
      demonstrates personal caring for a patient, the healing process is likely
      enhanced, and in that sense, physicians often promote the spirituality of the
      patient. However, recent proposals to extend the physician's task to that of
      assessing religion and directing the patient toward approved forms of
      spirituality are inappropriate. The languages of religion and science are
      radically different. The cultural body-mind split will not be solved by such
      simplistic solutions as having physicians endorse spirituality, which will result
      only in denigration of both medicine and religion. Physicians are encouraged to
      rely on clinically trained ministers for assistance in understanding the
      patient's state of mind or spirit and its possible effects on the course of
      illness and health.

PMID- 12008798
TI  - Evaluation of microleakage in cervical margins of various posterior restorative
      systems.
AB  - PURPOSE: The purpose of this in vitro study was to evaluate the microleakage and
      dye penetration patterns of various restorative systems in the cervical margins
      of Class II cavities using the dye penetration technique. MATERIALS AND METHODS:
      Ninety bovine incisors were selected and part of the crown was sectioned
      producing a standardized occlusogingival margin of 4 mm. Standardized Class II
      box cavities were designed on the mesial (MO) and distal (OD) surfaces with the
      gingival margin in dentin. The cavities were randomly divided into six groups (n
      = 30): group 1 (control), Etch & Prime 3.0 (Degussa AG) + Definite (Degussa AG);
      group 2, Prime & Bond NT (Dentsply De Trey) + Definite; group 3, Etch & Prime 3.0
      + flowable composite resin Wave (SDI) + Definite; group 4 (control), Prime & Bond
      NT + TPH Spectrum (Denstply De Trey); group 5, Etch & Prime 3.0 + TPH Spectrum;
      group 6, Prime & Bond NT + Wave + TPH Spectrum. After they were finished and
      polished, the specimens were subjected to 1500 thermal cycles in baths of 5
      degrees+/-2 degrees C and 55 degrees+/-2 degrees C with 60 seconds of dwell time
      for each bath. After the thermocycling, the specimens were sealed with acid
      resistant varnish, leaving a 1-mm window around the cervical margin interface,
      and immersed in 2% methylene blue buffered solution for 4 hours. Then the
      specimens were sectioned longitudinally in half and qualitatively evaluated under
      stereomicroscopy at 45 times magnification, using ranked scores for the dentin
      cervical margin (0-4). The dye penetration pattern (adhesive or dentinal) was
      also evaluated. The data were subjected to a reproducibility kappa test, and the
      mean of the three examiners' scores was analyzed by the Kruskal-Wallis
      nonparametric test and a multiple comparison nonparametric test. Fisher's exact
      test was used to evaluate the dye penetration pattern. RESULTS: The rank sums of
      the groups were expressed in decreasing order: group 4, 67.23a; group 3, 72.58ab;
      group 6, 78.43ab; group 5, 93.19bc; group 2, 112.97c; group 1, 113.52c.
      (Statistically significant differences are expressed by different superscript
      letters.) The results indicate that none of the systems used in this study was
      able to impede microleakage, and that the use of a flowable resin decreases the
      values of leakage only for Definite composite resin. The dye penetration pattern
      for the groups that used Prime & Bond NT was predominantly dentinal, whereas the
      pattern for Etch & Prime 3.0 groups was adhesive. CLINICAL SIGNIFICANCE: An
      ormocer-based resin that was developed to improve the physical properties of
      composite resin and a self-etching primer adhesive system obtained higher values
      of microleakage compared with a one-bottle adhesive system and a microhybrid
      composite resin. The flowable composite resin decreased the values of
      microleakage only for the ormocer-based resin.

PMID- 12008799
TI  - Effect of resin-coating technique on dentin tensile bond strengths over 3 years.
AB  - PURPOSE: The resin-coating technique has been developed to protect prepared
      dentin and underlying pulp tissue. The purpose of this study was to evaluate the
      resin-coated dentin bond durability over a period of 3 years of a resin cement
      and to compare it with two representative resin cements. MATERIALS AND METHODS:
      Ten bovine dentin specimens were tested for tensile bond strengths with each of
      the following three materials: CLAPEARL DC with a resin-coating technique (CDRC),
      Panavia 21 (PA21), and Super Bond C&B (SBCB) at 1 day, 6 months, 1 year, and 3
      years. Mean bond strengths were compared statistically by two-way analysis of
      variance and Fisher's PLSD test (p < .05). The mode of failure was classified by
      scanning electron microscope observation and analyzed using the Mann-Whitney U
      test. RESULTS: The 3-year bond strengths of all resin cements were significantly
      lower than those at the other experimental periods except for 1 year (p < .05).
      There was no significant difference in mean bond strength between CDRC and SBCB
      (p > .05). Regarding the fracture modes, in the case of CDRC, an increase in
      adhesive failure at the resin-dentin interface was observed as the time period
      lengthened. Statistical differences were observed between SBCB and the other
      materials at 1 year (p < .05) and between PA21 and the other materials at 3 years
      (p < .05). CLINICAL SIGNIFICANCE: The mean tensile bond strengths of the three
      resin cements to dentin decreased at different rates during the study; the rate
      at which the bond decreases is likely to affect the long-term durability of
      restorations.

PMID- 12008801
TI  - Talking with patients. Light-curing.

PMID- 12008803
TI  - Is tooth structure not sacred anymore?

PMID- 12008802
TI  - Metal-free dentistry: consumer generated or marketing hype?

PMID- 12008804
TI  - Dentin bonding.

PMID- 12008805
TI  - Esthetic treatment planning: the grid analysis system.
AB  - It is sometimes difficult to identify esthetic problems let alone pre-visualize
      an esthetic end-result. The Esthetic Grid Analysis is a system for analyzing the
      basic problems that detract from the concept of an attractive smile. A photograph
      is taken of the anterior teeth with the lips retracted. The upper and lower frame
      of the photograph is aligned parallel with the interpupillary line, assuming that
      the interpupillary line is parallel with the horizon. Where this is not the case,
      the vertical margins of the photograph are aligned parallel with the facial
      midline. Through orienting the photograph to the facial guidelines and
      incorporating the idealized positions of the incisal plane, highest lipline,
      midline axis, and proportionate contact areas, a grid is formed. The grid built
      from these components provides a method of demonstrating deviations from an
      esthetic arrangement of anterior teeth. CLINICAL SIGNIFICANCE: Integrating facial
      guidelines with the dental composition using a grid highlights deviations from
      the ideal. It thereby assists in the treatment planning process by communicating
      esthetic problems to the patient, laboratory personnel, and other specialists.

PMID- 12008806
TI  - Sensitivity and tooth whitening agents.
AB  - PURPOSE: Three commercially available dentist-prescribed home-applied bleaching
      systems were evaluated to identify the incidence of sensitivity and to compare
      the efficacy of whitening the maxillary anterior teeth of 18 patients. METHODS:
      NiteWhite Excel 2Z (Discus Dental), fx (Challenge Products), and Rembrandt Xtra
      Comfort (DenMat Corp.) were randomly assigned to six patients each. The fx
      product was used as a control since it was not advertised as a zero sensitivity
      product. The manufacturers' instructions for tray fabrication and use were
      followed while the patients bleached for 2 weeks. The patients kept a diary and
      were recalled at 1 week, 2 weeks, and 4 weeks. The shade change and the presence
      or absence of any sensitivity were evaluated at each recall. RESULTS: NiteWhite
      Excel 2Z was used for 83 days of treatment with the following percentage of
      positive sensitivity reported: 0% hot and cold, 2.4% throat sensitivity, 2.4%
      tongue sensitivity, and 25.3% gingival sensitivity. Rembrandt Xtra-Comfort was
      used for 84 days with 0% hot and cold, 0% throat, 11.9% tongue, and 27.4%
      gingival sensitivity reported. The fx product was used for 83 days and resulted
      in 14.5% hot and cold, 3.6% throat, 1.2% tongue, and 16.9% gingival sensitivity.
      All products lightened the teeth an average of eight shade tabs on the Vita
      guide. There was a statistically significant difference between the groups when
      comparing the presence of sensitivity (chi-squared test, p < .001) but not when
      comparing the shade tab change. CLINICAL SIGNIFICANCE: Of the products tested,
      all produced similar change in shade tab value, none were sensitivity free, but
      NiteWhite Excel 2Z and Rembrandt Xtra-Comfort did not produce thermal
      sensitivity.

PMID- 12008807
TI  - Higher-concentration carbamide peroxide effects on surface roughness of
      composites.
AB  - BACKGROUND: Ten percent carbamide peroxide has been used extensively within the
      dental profession for the purpose of bleaching teeth. Although this method has
      been successful, the use of higher-concentration carbamide peroxides (20-35%) for
      home bleaching has increased substantially in the past few years. The purpose of
      this study was to evaluate changes in surface roughness of a hybrid and a
      microfilled composite after exposure to bleaching agents containing higher
      concentrations of carbamide peroxide. MATERIALS AND METHODS: Sixty-eight
      circular, resin-based composite specimens (8 mm x 2 mm) were prepared against a
      Mylar surface. Half of the specimens were fabricated from a hybrid composite
      material and the other half with a microfilled composite. Specimens were polished
      with aluminum oxide finishing disks, divided into four groups, and then exposed
      either to 20% carbamide peroxide for 3 hours per day for 14 days or to 35%
      carbamide peroxide for 1 hour per day for 14 days. The mean surface roughness
      (Ra) was determined for each specimen before and after exposure to bleaching
      agents, using mechanical profilometry. Data were analyzed by two-way analysis of
      variance (ANOVA) for differences between composite type, carbamide peroxide
      concentrations, and interaction of the two factors with respect to average
      surface roughness. All data analysis was performed at alpha = 0.05. RESULTS: Mean
      change from baseline of surface roughness (Ra) of microfilled composite and 20%
      carbamide peroxide was -0.03 microm +/- 0.10 microm; microfilled composite and
      35% carbamide peroxide: 0.01 microm x 0.02 microm; hybrid composite and 20%
      carbamide peroxide: -0.43 microm x 0.91 microm; hybrid composite and 35%
      carbamide peroxide: -0.19 microm x 0.43 microm. Surface roughness of hybrid or
      microfilled composite did not change significantly from baseline with either
      concentration of carbamide peroxide (p = .300). CLINICAL SIGNIFICANCE: Higher
      concentration carbamide peroxide bleaching agents, used as intended by the
      manufacturer, pose no significant risk to resin composite restoration surfaces.

PMID- 12008808
TI  - Public preferences for anterior tooth variations: a web-based study.
AB  - PURPOSE: This study was undertaken to determine the public's preferences for five
      esthetic variations, with the goal of linking preferences to demographic data
      such as age, gender, country of residence, and race. MATERIALS AND METHODS: Using
      photo-editing software, five pairs of images with anterior tooth variations were
      put on a Web page with forms to collect demographic data and ranking of the image
      pairs. Opinions were solicited by sending out a large number of e-mails with a
      short study description and an invitation to access the Web page. The responses
      were tabulated and analyzed with logistic regression (alpha = 0.05). RESULTS:
      Valid responses were received from 2185 computer users in 45 countries. Because
      of the small number of respondents from most countries, only the responses from
      the United States and Canada (n = 1934) were analyzed. Variables collected were
      birth date, gender, race or ethnic background, and last dental visit. Analysis
      indicated that different variables were significant for different questions. Last
      dental visit and the interaction of gender and race were not significant in any
      of the models. Strongest preferences concerned diastema and midline shift and the
      weakest concerned whiteness and proportion. The largest minority view was the
      straight embrasures. Statistically significant differences were attributable to
      age, gender, and race. Females had stronger preferences in all conditions.
      Respondents younger than 40 years of age had stronger preferences for whiteness
      and against diastema, and whites strongly rejected the diastema. CLINICAL
      SIGNIFICANCE: This study provides guidelines about the public's preferences
      concerning some commonly encountered conditions in esthetic dentistry.

PMID- 12008809
TI  - Routine use of office gynecologic ultrasound.

PMID- 12008810
TI  - Renal sonography in the intensive care unit.

PMID- 12008811
TI  - Ultrasonographic estimation of fetal weight: acquiring accuracy in residency.
AB  - OBJECTIVE: Ultrasonographic imaging is considered an objective means for fetal
      weight estimation. The goals of this study were to determine the accuracy of
      ultrasonographic estimates of fetal'weight performed by residents in training and
      to ascertain how rapidly the residents gained proficiency in this regard.
      METHODS: A total of 300 ultrasonographic estimates of fetal weight and
      corresponding birth weight were collected and stratified into 4 groups by the
      level of residents' experience, from level 1 (inexperienced, with <6 months of
      exposure) to level 4 (advanced experience, with at least 24 months of training).
      The proportional difference between ultrasonographic estimates of fetal weight
      and birth weight was calculated for each case and grouped according to the level
      of training of the examiner. The derived data were compared by analysis of
      variance, linear regression, and chi2 test. RESULTS: Significant increases in the
      accuracy of ultrasonographic estimates of fetal weight were observed with
      advancing levels of resident experience (P< .0001). Overall, 30.6% of
      ultrasonographic estimates of fetal weight fell within 5% of birth weight, and
      60.6% fell within 10%. Among the least experienced residents (<6 months of
      training), 49.4% of estimates fell within 10% of birth weight; among those with 6
      to 11 months of experience, 53.5% of estimates fell within 10%; among those with
      12 to 23 months of experience, 64.1 % of estimates fell within 10%; and among the
      most experienced (>24 months), 73.6% of estimates fell within 10%. CONCLUSIONS:
      There is a learning curve for ultrasonographic estimates of fetal weight, with a
      significant decrease in the percent error seen with advancing training among
      residents, reaching acceptable levels of more than 70% of estimates within 10% of
      birth weight after 24 months of ultrasonographic experience.

PMID- 12008812
TI  - Value of a complete sonographic survey in detecting fetal abnormalities:
      correlation with perinatal autopsy.
AB  - OBJECTIVE: To determine the sensitivity of using a complete anatomic sonographic
      survey in detecting fetal abnormalities via correlation with perinatal autopsy
      results. METHODS: All perinatal autopsies (1994-2001) with positive findings for
      at least 1 fetal abnormality and performed by a single perinatal pathologist at
      our institution were retrospectively reviewed. From these cases, singleton
      fetuses who received prenatal sonography solely in our unit were identified. The
      sensitivity of sonography in detecting anomalous fetuses as well as fetal
      abnormalities and abnormalities by organ system was determined. Abnormalities
      were classified as major or minor In addition, findings from sonography and
      autopsy were compared, and their correlation was assigned to 1 of 3 categories.
      RESULTS: Of 88 fetuses identified, 85 had 1 or more abnormal structural
      sonographic findings (sensitivity for fetuses with anomalies, 97%). A total of
      372 separate abnormalities were found on autopsy; of the 299 major and 73 minor
      abnormalities, prenatal sonography showed 224 (75%) and 13 (18%), respectively.
      There was either complete agreement or only minor differences between sonographic
      and autopsy findings in 57 (65%) of 88. The sensitivity of sonography in
      identifying abnormalities was greater than 70% in these systems: central nervous
      system, cardiac system, urinary system, extremities, genitalia, ribs, and
      hydrops. CONCLUSIONS: In experienced hands, sonography has 97% sensitivity in
      detecting anomalous fetuses when compared with perinatal autopsy results.
      Although the sensitivity of sonography in detecting major fetal abnormalities is
      75%, the sensitivity for minor abnormalities is poor, even when using a complete
      anatomic sonographic survey. Although it has limitations, this type of survey is
      invaluable for both patients and physicians in diagnosing fetal abnormalities.

PMID- 12008813
TI  - Improved sonographic visualization of the appendix with a saline enema in
      children with suspected appendicitis.
AB  - OBJECTIVE: To determine whether abdominal sonography after a saline enema can
      identify the appendix that is not visualized at graded compression sonography in
      children with suspected appendicitis. METHODS: High-frequency compression
      sonography was prospectively performed in 120 consecutive children with suspected
      appendicitis; the appendix was not identified in 27 of these patients. Among the
      27 patients with a nonvisualized appendix, abdominal sonography after a saline
      enema was performed in 12 to identify the appendix. RESULTS: Abdominal sonography
      after the saline enema revealed the appendix in all 12 children in whom the
      appendix was not visualized at graded compression sonography. A normal appendix
      was found in 11 children, and acute appendicitis confined to the appendiceal tip
      was found in 1. The appendix was located in the pelvis (n = 5), posterior to the
      cecum (n = 4), posterior to the ileum (n = 2), and anterior to the ileum (n = 1).
      The appendix could be identified by using a window of the saline-filled sigmoid
      colon (n = 5), saline-filled cecum (n = 4), and saline-filled terminal ileum (n =
      2). CONCLUSIONS: Abdominal sonography after a saline enema is a helpful technique
      for depiction of the appendix that is not visible at graded compression
      sonography in children with suspected appendicitis. Key words: appendix,
      sonography; appendicitis; children, gastrointestinal tract.

PMID- 12008814
TI  - Renal sonography in the intensive care unit: when is it necessary?
AB  - OBJECTIVE: To evaluate the efficacy of renal sonography performed in intensive
      care units on patients with the diagnosis of acute or acute-on-chronic renal
      failure. METHODS: We reviewed all renal sonograms performed in our institution
      during 1 year on critically ill patients for evaluation of renal failure. Renal
      failure was defined as a serum creatinine level greater than 1.5 mg/dL or an
      increase of greater than 20% from the baseline creatinine level. Exclusion
      criteria included patient age younger than 18 years and signs or symptoms of
      obstructive uropathy. Using the electronic medical record, we recorded patient
      age, sex, blood urea nitrogen level, serum creatinine level, blood urea nitrogen
      creatinine ratio, and clinical indication for intensive care unit admission.
      Sonographic reports were reviewed for the presence or absence of hydronephrosis.
      The total cost of these examinations was estimated with the use of Medicare
      reimbursement rates for 2000. RESULTS: One hundred five renal sonographic
      examinations were performed on 104 patients meeting all inclusion criteria. Only
      1 study had positive results for hydronephrosis, which was graded as mild.
      Incidental findings not immediately affecting patient care and including ascites
      and simple renal cysts were identified in 91 patients. The estimated total cost
      of the examinations was $13,350.75. CONCLUSIONS: In critically ill patients with
      acute renal failure and no physical findings suggesting obstructive uropathy,
      renal sonography to evaluate for hydronephrosis is probably not indicated. This
      holds true regardless of patient age, sex, medical or surgical disposition, and
      blood urea nitrogen-creatinine ratio.

PMID- 12008815
TI  - Utility of targeted sonography in the evaluation of focal breast pain.
AB  - OBJECTIVE: To determine the utility of targeted sonography in the evaluation of
      patients with focal breast pain. METHODS: From January 1995 through December
      1999, 110 targeted sonographic examinations were performed in 99 patients for
      evaluation of focal breast pain in the absence of an associated palpable mass.
      The sonographic, mammographic, and clinical findings were reviewed. The hospital
      pathology database was searched to identify any interval cancers and false
      negative interpretations. RESULTS: No cancer was identified in any of the 110
      examinations. Eighty-five (77.3%) of the examinations had negative findings.
      Cysts were identified in 15 cases (13.6%), and 3 solid masses (2.7%) were
      identified. Two of these 3 solid masses had biopsies and were shown to be benign,
      whereas the third mass was followed for 29 months without change. Most patients
      were premenopausal, had no family or personal history of breast cancer, and were
      not taking exogenous hormones. Eighty-five patients (77%) were referred by
      primary care physicians. CONCLUSIONS: In patients with focal breast pain without
      an associated palpable mass, sonography may be more useful for patient
      reassurance than for cancer detection.

PMID- 12008816
TI  - Sonographic morphology of infiltrating breast carcinoma: relationship with the
      shape of the hyaluronan extracellular matrix.
AB  - OBJECTIVE: To compare the shape of the sonographic image of invasive breast
      cancer with the shape of the corresponding histopathologic section stained for
      components of the extracellular matrix, hyaluronan, and collagen. METHODS: We
      studied 22 cases of breast carcinoma. Among them, 13 were visible on both
      sonography and mammography, whereas 9 were visible only on sonography. We
      compared the sonographic images with the histologic sections of the same
      carcinomas after staining with alcian blue for hyaluronan and Masson trichrome
      for collagen. RESULTS: We have shown that the shape of the sonographic image of
      breast cancer is similar to the shape of its hyaluronan extracellular matrix.
      CONCLUSIONS: This finding explains why breast sonography is so sensitive for
      detection of invasive carcinoma and why some invasive cancers are not visible on
      mammography.

PMID- 12008817
TI  - Sonography in primary hyperparathyroidism: review with emphasis on scanning
      technique.
AB  - OBJECTIVE: To review the sonographic features and focused sonographic scanning
      techniques that may assist in the preoperative localization of parathyroid
      adenomas in patients with primary hyperparathyroidism. METHODS: The sonographic
      findings were reviewed in 54 of 58 consecutive patients with pathologically
      proven parathyroid adenomas. A systematic scanning approach including real-time
      gray scale, color and power Doppler, and graded compression gray scale imaging
      was used in all patients. RESULTS: Fifty-four (93%) of 58 proven adenomas were
      correctly identified by sonography. Gray scale imaging alone was sufficient for
      identifying 26 (100%) of 26 large (> or =1-cm) and 3 (11%) of 25 small (<1-cm)
      parathyroid adenomas. However, for 25 (89%) of 28 small adenomas, a combination
      of color and power Doppler and graded compression real-time gray scale imaging
      was required for sonographic localization and identification. CONCLUSIONS:
      Knowledge of typical locations and characteristic imaging features, as well as a
      systematic scanning approach, can result in accurate preoperative sonographic
      localization of parathyroid adenomas.

PMID- 12008818
TI  - Sonographic imaging of foramen ovale electrodes.
AB  - OBJECTIVE: In patients with medically intractable partial epilepsy of
      mesiotemporal origin, video electroencephalographic monitoring with foramen ovale
      electrodes is necessary to plan neurosurgical interventions. Imaging of these
      electrodes after implantation hitherto required conventional radiography,
      magnetic resonance imaging, or computed tomography of the skull. These methods
      are expensive. Therefore, the aim of our work was to show the capability of more
      cost-effective transcranial B-mode sonography for visualization of the
      electrodes. METHODS: In this pilot study, a 42-year-old female patient with
      implanted foramen ovale electrodes was examined transtemporally with a 2-MHz
      sector transducer to visualize the intracranially implanted
      electroencephalographic recording device. RESULTS: Foramen ovale electrodes could
      be detected easily in the patient, and bedside monitoring of explantation was
      possible. CONCLUSIONS: We were able to show the applicability of transcranial B
      mode sonography for visualization of foramen ovale electrodes in preoperative
      electroencephalographic monitoring of patients with epilepsy. Further evaluation
      of this method in additional patients will follow.

PMID- 12008819
TI  - Twinkling artifact in color Doppler imaging of the orbit.
AB  - OBJECTIVE: To show an artifact related to color Doppler flow imaging of the
      orbit. METHODS: Three patients with strongly reflective structures in the orbit
      were selected from those routinely referred by clinicians for color Doppler
      ultrasonography of the orbit. Gray scale and color flow images were obtained with
      a 7.5-MHz linear array probe for a region with strongly reflective structures. A
      spectral display was acquired to confirm the presence of blood flow. RESULTS: One
      patient had a metallic foreign body just behind the bulb; another had
      calcification within the irregular mass of phthisis bulbi; and the third had
      hyperechoic drusen in the periphery of the intraocular melanoma. The color
      mosaic, suggesting the presence of blood flow, was detected beyond all
      hyperechoic structures. Close vertical bands with no outer wrapping were detected
      in the spectrum display, obtained by placing the sample volume on the region of
      color flow. The artificial color flow was recognized as a color Doppler twinkling
      artifact. CONCLUSIONS: The color flow beyond the strongly reflecting structures
      in the orbit might be mistakenly interpreted as real blood flow if an examiner is
      not familiar with the artifact. It should prompt further imaging with spectral
      Doppler ultrasonography.

PMID- 12008820
TI  - Persistent hyperplastic primary vitreous and von Hippel-Lindau disease:
      contribution of color Doppler ultrasonography.

PMID- 12008821
TI  - Congenital absence of the portal vein with an intrahepatic inferior vena cava
      branch showing hepatopetal flow.

PMID- 12008822
TI  - In utero diagnosis of isolated obstructed supracardiac total anomalous pulmonary
      venous connection.

PMID- 12008823
TI  - Fetal urethral obstruction with spontaneous rupture of the bladder and creation
      of a gastroschisis.

PMID- 12008824
TI  - Sonographic appearance of acute panniculitis involving the breasts.

PMID- 12008825
TI  - Mammographic and sonographic findings of a breast subcutaneous hemangioma.

PMID- 12008826
TI  - Case 1. Persistent right umbilical vein, isolated finding.

PMID- 12008827
TI  - Case 2. Biliary hamartomas (von Meyenberg complex).

PMID- 12008828
TI  - Case 3. Thrombosed, partially calcified venous malformation associated with
      subdural hematoma.

PMID- 12008829
TI  - Case 4. Acute autoimmune hepatitis with "collapse".

PMID- 12008830
TI  - Case 5. Beckwith-Wiedemann syndrome.

PMID- 12008831
TI  - Case 6. Sarcoidosis.

PMID- 12008832
TI  - Case 7. Hemorrhagic ovarian cyst.

PMID- 12008833
TI  - Case 8. Cloacal anomaly.

PMID- 12008834
TI  - Case 9. Incarcerated uterus.

PMID- 12008835
TI  - Case 10. Adrenal pheochromocytoma in pregnancy.

PMID- 12008836
TI  - Case 11. Benign leiomyoma.

PMID- 12008837
TI  - Case 12. Absent septum or septo-optic dysplasia (magnetic resonance imaging not
      yet performed).

PMID- 12008844
TI  - The road not taken.

PMID- 12008845
TI  - Preoperative planning for revision total hip arthroplasty.
AB  - Similar to total hip arthroplasty (THA), preoperative planning is more important
      for revision THA and includes a thorough clinical evaluation (ie, patient
      history, physical examination, and laboratory tests, including aspiration and
      culture) as well as radiographic assessment (ie, for changes in bone loss and
      quality, for leg length, and for templating to choose the correct components).
      Similar to primary THA, preoperative planning for revision THA must include the
      inherent possibility of failure. Careful planning of the current technology and
      expertise to perform THA will help minimize potential problems. The essence of
      preoperative planning in revision THA can be summed up simply: Be prepared.

PMID- 12008846
TI  - Bone assessment and reconstruction in revision hip surgery.
AB  - As a result of septic and aseptic complications, total hip replacements can fail
      and consequently have finite life expectancies. One of the most challenging
      aspects of revision surgery is the management of bone loss. We present a
      classification that maps the severity of bone loss with a variety of
      reconstructive options, which include cemented and uncemented fixations. This
      classification has been used successfully to guide preoperative planning, to help
      determine intraoperative needs (implants, specialized equipment, and bone
      grafts), and to help prepare the patient about the postoperative rehabilitation
      course.

PMID- 12008847
TI  - Cemented femoral revision: technique and outcome.
AB  - Long-term pain relief and improved function in patients with failed or infected
      hip replacement, or, occasionally for patients with impending surgical failure,
      are the goals of total hip revision arthroplasty. Cement techniques for femoral
      and reconstructions in patients needing total hip revision are discussed in this
      article. Advantages of cemented technique include the ability to incorporate
      antibiotics into the cement during reimplantation following periprosthetic
      infection. Cemented technique is also preferable over cementless techniques when
      there is extensive diaphyseal bone loss, which precludes predictable biologic
      fixation. Cement-within-cement technique is indicated for well-fixed cemented
      femoral components that require revision for instability, improved acetabular
      exposure, equalization of leg lengths, or damage to a monoblock femoral head.

PMID- 12008848
TI  - Proximal femoral replacement.
AB  - Reconstruction of the proximal femur after extensive bone loss is clinically
      challenging. Options for reconstruction depend on the classification and extent
      of the proximal femoral defect. Although reconstitution of the native proximal
      femoral bone stock are the traditional goals of most revision techniques for the
      proximal femur, these techniques lose their effectiveness after numerous
      revisions due to the severe loss of a sufficient amount of structural bone needed
      to reconstruct the femur and abductor attachment. Consequently, the proximal
      femoral bone becomes fragile with extensive bone loss despite bone grafting.
      Techniques that use allograft-prosthetic composite and femoral megaprosthesis can
      successfully restore a patient's ambulatory ability despite the absence of
      significant portions of the proximal femur.

PMID- 12008849
TI  - Revision total hip arthroplasty using a cementless modular femoral hip design.
AB  - The difficulty in selecting the "ideal" components for revision total hip
      arthroplasty is one factor leading to poor outcomes. For femoral hip components,
      loosening rates of femoral revision have been reported with different types of
      designs. Because of improved rates with more porous components, the use of
      cementless femoral revision is highly attractive. This article describes a
      cementless femoral revision component, the ZMR system, which addresses the
      challenges and design goals of revision as well as surgical philosophy: off-the
      shelf flexibility, proximal-distal extensive fixation, restoration of kinematics
      (offset, let lengths, anteversion, and muscle tensioning), and implant integrity.

PMID- 12008850
TI  - Revision of failure acetabular components with cementless acetabular components.
AB  - Outcomes of cemented acetabular components show unacceptably high rates of
      loosening over the short-term, and increased failure over the long term. The use
      of uncemented acetabular components with porous coatings and supplemental screw
      fixation has improved the success rates of revision surgery with bone loss.
      Intermediate follow-up results of uncemented acetabular components for revision
      surgery suggest excellent outcomes with superior fixation compared with cemented
      components. Use of large components that rely on the posterior column and
      acetabular dome for fixation appear to function satisfactorily, even in a
      significantly bone deficient acetabulum.

PMID- 12008851
TI  - Beyond cementless hemispherical sockets.
AB  - One of the major goals of acetabular revision is achieving stability. To achieve
      intimate contact between the implant and host bone, which is critical for
      stability since bone ingrowth requires the absence of micromotion, the implant
      must match the defect or be able to bridge the defect. Hemispherical sockets can
      achieve long-term implant fixation in acetabular defects that are not extensive,
      whereas structural allografts are associated with long-term failure and reliance
      on them dooms the implant to failure. Increasing bone loss requires the use of
      implants that may not be hemispherical, such as the Oblong Cup, or devices that
      bridge the defect such as an antiprotrusio cage or Triflange Cup.

PMID- 12008852
TI  - Acetabular revision using grafts and cages.
AB  - Principles of acetabular revision include stable bone coverage that can support
      the new acetabular component, restoration of the anatomy and bone stock for
      future revisions, and equalization of leg length. Achieving these goals depends
      on the severity of the pelvic defect. Classification of these acetabular defects
      is critical to optimal treatment choice. A classification formulated by the
      authors of this paper and based on proven Severity Instrument methodology has
      been applied effectively at their institutions after meeting reliability and
      validation criteria. Approaches to acetabular revision based on this
      classification have resulted in good outcomes.

PMID- 12008853
TI  - A porous tantalum trabecular metal: basic science.
AB  - Conventional materials used for orthopedic reconstruction implants limit the
      design of new and improved implants. Solid metal is rigid. Porous fixation
      surfaces have low volumetric porosity available for biologic ingrowth and low
      frictional characteristics for initial implant stability and have to be bonded to
      solid-metal substrates. New porous structural biomaterials have been developed to
      help advance the current generation of prostheses and address unresolved clinical
      applications. Tantalum trabecular metal offers several advantages over other
      current conventional materials used for implants by its uniformity and structural
      continuity, strength, low stiffness, high porosity, and high coefficient of
      friction.

PMID- 12008854
TI  - Clinical applications of Trabecular Metal.
AB  - Trabecular Metal (porous tantalum) offers a viable solution to several challenges
      in orthopedic reconstructive surgery, including monoblock acetabular cups,
      avascular necrosis intervention devices, and total hip reconstruction in
      situations of massive femoral bone loss. Porous tantalum approaches the ideal
      biomaterial: it is porous, strong, flexible, and biocompatible. For use in
      components for total hip arthroplasty, porous tantalum provides a substitute for
      lost bone, immediate bone loading, bone ingrowth, and soft-tissue attachment. It
      can be machine-shaped into custom designs in situations of massive bone loss.

PMID- 12008855
TI  - Periprosthetic fractures of the femur following hip arthroplasty.
AB  - Periprosthetic femoral fractures are one of the leading causes of revision total
      hip arthroplasty. Risk factors for these fractures include intraoperative factors
      (ie, use of cemented technique and host factors, such as osteoporosis and
      osteolysis) and postoperative factors (ie, osteolysis and trauma). This article
      discusses prevention, evaluation, management, and technique issues of these
      fractures. A final section discusses the author's preferred treatment choice of
      these fractures, based on an algorithm developed by Duncan and Masri.

PMID- 12008856
TI  - Dislocation following revision total hip arthroplasty.
AB  - Dislocation is a relatively common complication following revision total hip
      arthroplasty. Risk factors include surgical approach, gender, underlying
      diagnosis, comorbidities, surgical experience, and previous surgery; for later
      dislocations, risk factors include wear/deformation of polyethylene, trauma, and
      decreased muscle strength. Prevention and precaution are the watchwords for
      dislocations following revision total hip arthroplasty. For dislocations that do
      occur, treatment rests first on identifying the source of instability. Most
      dislocations can be managed by closed reduction. Constrained components may
      increase success rates, but only for appropriate indications. Prevention and
      treatment of dislocations following revision total hip arthroplasty are discussed
      in this article.

PMID- 12008857
TI  - Stavudine-associated peripheral neuropathy in zidovudine-naive patients: effect
      of stavudine exposure and antiretroviral experience.
AB  - A post hoc analysis of safety data from study protocol NZT40012 assessed the
      incidence of conditions defined by the Centers for Disease Control and Prevention
      in 86 zidovudine-naive, antiretroviral-experienced patients with HIV-1 infection
      who responded poorly (plasma HIV-1 RNA > 1000 copies/mL) despite at least 4
      months' treatment with stavudine-containing regimens. Peripheral neuropathy
      occurred in 21%; other conditions were seen less frequently (candidiasis [13%],
      herpes zoster [12%], diarrhea lasting > 1 month [9%], Pneumocystis carinii
      pneumonia [9%], and wasting syndrome [8%]). The incidence of peripheral
      neuropathy rose significantly with the number of drugs comprising treatment
      regimens (> or = 4 vs 1-3; P = .013) and tended to be higher in patients with
      longer exposure to stavudine (29% with > or = 24 months' exposure vs 13% with <
      24 months). Because peripheral neuropathy was observed with such high frequency,
      vigilance for signs and symptoms of this condition appears warranted if stavudine
      containing regimens are to be continued.

PMID- 12008858
TI  - Selective serotonin reuptake inhibitor discontinuation syndrome: a review.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed in the
      treatment of depression and anxiety, as well as obsessive-compulsive, eating, and
      impulse-control disorders. Paralleling their widespread use has been an increase
      in adverse-effect reports not noted during short-term efficacy studies.
      Significant among these adverse effects is SSRI discontinuation syndrome, which
      follows the interruption of extended treatment or a reduction in drug dosage and
      entails somatic and psychological symptoms. These self-limiting symptoms resolve
      on reintroduction of the drug and cannot be explained as a remanifestation of the
      original disorder. To facilitate proper diagnosis and avoid unnecessary
      therapeutic or diagnostic interventions, all physicians who prescribe SSRIs
      should become familiar with these symptoms. The most appropriate approach to
      therapy for discontinuation syndrome involves educating patients and reassuring
      them that this is a reversible condition, reinstating the original SSRI, and
      further slowing the rate of tapering.

PMID- 12008859
TI  - Efficacy of anakinra in bone: comparison to other biologics.
AB  - Three biologic therapies significantly slow radiographic progression in active
      rheumatoid arthritis. This paper compares the effects of anakinra, a recombinant
      human interleukin-1 receptor antagonist, with those of etanercept and infliximab,
      two drugs that target tumor necrosis factor-alpha. A Medline search identified
      controlled clinical trials that included radiographic progression as an endpoint.
      Anakinra 30 to 150 mg subcutaneously each day for 24 weeks was significantly more
      effective than placebo in slowing progression of erosion, joint-space narrowing,
      and total composite scores, as assessed by the Genant method, and erosive joint
      count, as assessed by the Larsen method. Erosion scores were slowed even further
      during a 24-week extension. Etanercept 25 mg subcutaneously twice weekly and
      infliximab 3 to 10 mg/kg intravenously every 4 or 8 weeks also slowed progressive
      joint damage, but these agents were studied under different study designs,
      patient populations, and radiographic assessments than those used in the anakinra
      study. Despite these differences, however, each biologic therapy appeared to slow
      progressive joint damage. In some studies, control of clinical symptoms did not
      correlate with slowing of radiographic progression. Agents that block interleukin
      1 or tumor necrosis factor-alpha appear similarly effective in slowing
      radiographic progression in patients with active rheumatoid arthritis. Treatment
      strategies for this disease may need to consider clinical symptoms, progressive
      joint damage, and long-term safety effects separately.

PMID- 12008860
TI  - Hypericum perforatum versus fluoxetine in the treatment of mild to moderate
      depression.
AB  - In a randomized, controlled, double-blind trial, 70 patients (mean age, 49.7
      years) suffering from mild to moderate depression received one tablet of either
      St. John's Wort (Hypericum perforatum) extract (Calmigen) or fluoxetine
      hydrochloride (Prozac) twice a day for 6 weeks. Efficacy was determined according
      to the 17-item Hamilton Rating Scale for Depression (HAMD), the von Zerssen
      depression scale (DS), Clinical Global Impression (CGI), and patients' overall
      evaluation. Significant decreases (P<.001) of 50% in the Hypericum group and 58%
      in the fluoxetine group in the HAMD score and of 42% and 52% on the DS spoke to
      the efficacy of both medications. The Hypericum extract achieved 83% of the
      efficacy of fluoxetine on the HAMD and 78% on the DS. Assessments by physicians
      (CGI) and patients indicated considerable improvement with no between-treatment
      differences. Of the 9 dropouts (13%), 2 in the Hypericum group and 2 in the
      fluoxetine group were due to adverse reactions. Safety evaluations demonstrated
      only minor changes. The Hypericum preparation tested in this study is
      therapeutically equivalent to fluoxetine and is therefore a rational alternative
      to synthetic antidepressants.

PMID- 12008861
TI  - Impulse magnetic-field therapy for erectile dysfunction: a double-blind, placebo
      controlled study.
AB  - This double-blind, placebo-controlled study assessed the efficacy of 3 weeks of
      impulse magnetic-field therapy for erectile dysfunction (ED). Twenty volunteers
      who suffered from ED or orgasmic disturbances were randomly assigned to either
      active treatment or placebo (n = 10 each). Efficacy was assessed in terms of
      intensity and duration of erection, general well-being, sexual activity, and warm
      sensation in the genital area. In the active-treatment group, all efficacy
      endpoints were significantly improved at study end (P < or = .01), with 80%
      reporting increases in intensity and duration of erection, frequency of genital
      warmth, and general well-being. The remaining 20%, who experienced minor
      improvements, were found to have an influenza-like infection after the study that
      may have influenced their results. Only 30% of the placebo group noted some
      improvement in their sexual activity; 70% had no change. No side effects were
      reported.

PMID- 12008862
TI  - Twice-daily and once-daily nedocromil sodium 2% ophthalmic solution for the
      treatment of seasonal allergic conjunctivitis.
AB  - In this 8-week open-label, prospective study, 30 patients with grass pollen
      allergy and ocular itching instilled nedocromil sodium 2% ophthalmic solution
      twice daily for a 5-day baseline period, followed by once-daily dosing
      thereafter. Physicians assessed clinical signs after the twice-daily period and
      after weeks 1 and 3 of the once-daily period; patients rated ocular symptoms
      daily. Use of specified rescue medication was permitted. Symptom scores for
      ocular itching, stinging, redness, swelling, burning, tearing, and light
      sensitivity did not differ significantly between the dosage periods. Scores for
      erythema, edema, conjunctival injection, and the entire conjunctiva decreased
      slightly during once-daily administration; discharge scores were unchanged. Of
      the 20 patients who used rescue medication, only 5 increased their usage by more
      than two doses per week during the once-daily period. Eighty-three percent of
      patients were willing to continue the once-daily regimen during the next allergy
      season. Physicians rated overall control of seasonal allergic conjunctivitis with
      once-daily administration as "good" or "moderate" in 100% of the patients; 93% of
      patients applied those ratings themselves. Nedocromil sodium 2% ophthalmic
      solution instilled once daily maintains control of symptoms in patients who are
      established on a twice-daily regimen.

PMID- 12008863
TI  - Inexpensive isolation of beta-D-glucopyranosidase from alpha-L
      arabinofuranosidase, alpha-L-rhamnopyranosidase, and o-acetylesterase.
AB  - Beta-D-Glucopyranosidase (betaG, EC 3.2.1.21) has been isolated from some
      collateral activities, alpha-L-arabinofuranosidase (Ara, EC 3.2.1.55), alpha-L
      rhamnopyranosidase (Rha, EC 3.2.1.40), and o-acetylesterase (Est, EC 3.1.1.53),
      using a commercial enzyme preparation and a simple method economically
      sustainable for the food industry. The procedure comprises precipitation of
      extraneous substances by adding ethanol and CaCl2, ultrafiltration, and
      adsorption, first on bentonite and then on chitosan. The results obtained were
      the complete isolation of betaG from the above-mentioned activities, a drastic
      reduction in extraneous compounds, such as brown substances and polysaccharides,
      and a slight increase in purification.

PMID- 12008864
TI  - Effect of starting xylose concentration on the microaerobic metabolism of
      Debaryomyces hansenii: the use of carbon material balances.
AB  - Xylitol production by Debaryomyces hansenii NRRL Y-7426 was performed on
      synthetic medium varying the initial xylose concentration between 50 and 300 g/L.
      The experimental results of these tests were used to investigate the effect of
      substrate level on xylose consumption by this yeast. Satisfactory values of
      product yield on substrate (0.74-0.83 g/g) as well as volumetric productivity
      (0.481-0.694 g/L x h) were obtained over a wide range of xylose levels (90-200
      g/L), while a worsening of kinetic parameters took place at higher concentration,
      likely due to a substrate inhibition phenomenon. The metabolic behavior of D.
      hansenii was studied, under these conditions, through a carbon material balance
      to estimate the fractions of xylose consumed by the cell for different activities
      (xylitol production, biomass growth, and respiration) during the lag,
      exponential, and stationary phases.

PMID- 12008865
TI  - Oxidation of kojic acid catalyzed by manganese peroxidase from Ceriporiopsis
      subvermispora in the absence of hydrogen peroxide.
AB  - We have previously reported the oxidation of kojic acid catalyzed by manganese
      peroxidase (MnP) from Ceriporiopsis subvermispora. This reaction is strictly
      dependent on Mn(II), although it does not require the addition of hydrogen
      peroxide. We have extended these studies because this reaction can be considered
      as a model system for the in situ generation of hydrogen peroxide in natural
      environments. We show here that oxidation of kojic acid with horseradish
      peroxidase (HRP) plus hydrogen peroxide or with manganic acetate rendered a
      product with identical chromatographic and spectral properties as the one
      obtained in the reaction catalyzed by MnP. The initial lag observed in the latter
      reaction decreased significantly upon UV irradiation of the substrate. On the
      other hand, ascorbic acid increased the lag and did not affect the yield of the
      reaction. The superoxide anion trapping agents glutathione, nitroblue
      tetrazolium, and superoxide dismutase markedly affected the reaction. In
      contrast, addition of the hydroxyl radical scavengers mannitol and salicylic acid
      had no effect. Based on these results, a mechanism for the MnP-catalyzed reaction
      is proposed.

PMID- 12008866
TI  - A model explaining declining rate in hydrolysis of lignocellulose substrates with
      cellobiohydrolase I (cel7A) and endoglucanase I (cel7B) of Trichoderma reesei.
AB  - It is commonly observed that the rate of enzymatic hydrolysis of solid cellulose
      substrates declines markedly with time. In this work the mechanism behind the
      rate reduction was investigated using two dominant cellulases of Trichoderma
      reesei: exoglucanase Cel7A (formerly known as CBHI) and endoglucanase Cel7B
      (formerly EGI). Hydrolysis of steam-pretreated spruce (SPS) was performed with
      Cel7A and Cel7B alone, and in reconstituted mixtures. Throughout the 48-h
      hydrolysis, soluble products, hydrolysis rates, and enzyme adsorption to the
      substrate were measured. The hydrolysis rate for both enzymes decreases rapidly
      with hydrolysis time. Both enzymes adsorbed rapidly to the substrate during
      hydrolysis. Cel7A and Cel7B cooperate synergistically, and synergism was
      approximately constant during the SPS hydrolysis. Thermal instability of the
      enzymes and product inhibition was not the main cause of reduced hydrolysis
      rates. Adding fresh substrate to substrate previously hydrolyzed for 24 h with
      Cel7A slightly increased the hydrolysis of SPS; however, the rate increased even
      more by adding fresh Cel7A. This suggests that enzymes become inactivated while
      adsorbed to the substrate and that unproductive binding is the main cause of
      hydrolysis rate reduction. The strongest increase in hydrolysis rate was achieved
      by adding Cel7B. An improved model is proposed that extends the standard endo-exo
      synergy model and explains the rapid decrease in hydrolysis rate. It appears that
      the processive action of Cel7A becomes hindered by obstacles in the
      lignocellulose substrate. Obstacles created by disordered cellulose chains can be
      removed by the endo activity of Cel7B, which explains some of the observed
      synergism between Cel7A and Cel7B. The improved model is supported by adsorption
      studies during hydrolysis.

PMID- 12008867
TI  - Possibilities for recycling cellulases after use in cotton processing: part I:
      Effects of end-product inhibition, thermal and mechanical deactivation, and
      cellulase depletion by adsorption.
AB  - Preliminary recycling experiments with cellulase enzymes after cotton treatments
      at 50 degrees C showed that activity remaining in the treatment liquors was
      reduced by about 80% after five recycling steps. The potential problems of end
      product inhibition, thermal and mechanical deactivation, and the loss of some
      components of the cellulase complex by preferential and or irreversible
      adsorption to cotton substrates were studied. End-product inhibition studies
      showed that the build-up of cellobiose and glucose would be expected to cause no
      more than 40% activity loss after five textile treatment cycles. Thermal and
      mechanical treatments of cellulases suggested that the enzymes start to be
      deactivated at 60 degrees C and agitation levels similar to those used in textile
      processing did not cause significant enzyme deactivation. Analysis of cellulase
      solutions, by fast protein liquid chromatography, before and after adsorption on
      cotton fabrics, suggested that the cellobiohydrolase II (Cel6A) content of the
      cellulase complex was reduced, relative to the other components, by preferential
      adsorption. This would lead to a marked reduction in activity after several
      treatment cycles and top-up with pure cellobiohydrolase II would be necessary
      unless this component is easily recoverable from the treated fabric.

PMID- 12008869
TI  - A strategy for critical care information.

PMID- 12008868
TI  - Possibilities for recycling cellulases after use in cotton processing: part II:
      Separation of cellulases from reaction products and released dyestuffs by
      ultrafiltration.
AB  - The adsorption and activity of a total cellulase (Trichoderma reesei) was
      measured and compared on undyed and dyed cotton fabrics. Recovery of enzymes from
      the reaction mixture and by desorption from the cotton substrate was evaluated.
      About 80% of the initial protein could be recovered. The removal of released
      products (soluble reducing sugars and dyes) from the treatment liquor and
      subsequent concentration of cellulase proteins was performed using an
      ultrafiltration membrane. Strong protein-dye interactions made it impossible to
      separate efficiently the dyes from the enzyme-containing treatment liquors. The
      use of surfactants did not enhance cellulase desorption from cotton fabric.
      Although anionic surfactants have a deactivating effect on cellulases, this
      effect seems to be reversible, since after ultrafiltration the cellulase activity
      was similar to that of enzymes desorbed with buffer only. Humicola insolens
      cellulases were shown to be much more sensitive to anionic surfactant than T.
      reesei cellulases. The use of cellulases that bind reversibly to cellulose is
      suggested for achieving more efficient cellulase recycling and for reducing
      backstaining by dye-cellulase complexes.

PMID- 12008870
TI  - National Patients Access Team, Critical Care Programme--Weaning and Long-Term
      Ventilation Sub Group.

PMID- 12008871
TI  - Improvements for patients in critical care.

PMID- 12008872
TI  - The World Federation of Critical Care Nurses has arrived.

PMID- 12008873
TI  - Utilizing TISS to differentiate between intensive care and high-dependency
      patients and to identify nursing skill requirements.
AB  - INTRODUCTION: An identification system utilizing the therapeutic intervention
      scoring system (TISS) was developed to differentiate between intensive care and
      high-dependency unit (HDU) patients. OBJECTIVE: To overcome the staff recruitment
      and retention problem, ward nursing staff were recruited into the unit. To ensure
      patient care requirements did not exceed nursing skill level, TISS was utilized
      to differentiate ICU from HDU patients and to identify nursing skill
      requirements. METHOD: All patients admitted to the unit over a 23-month period
      were concurrently TISS scored utilizing TISS -76 on admission (O/A), at 4-6
      hours, day 1, day 2 and on discharge. Concurrent data on age, medical history,
      type of surgery and length of stay were collected. RESULTS: There were a total of
      450 patients. Interventions utilized were mainly 1-, 2- and 3-point TISS values.
      The study identified the HDU patient group as being older, having a higher
      incidence of cardiac history and a shorter length of stay. The ICU patient group
      was identified as having undergone more major surgery. CONCLUSION: TISS is an
      effective triage tool for differentiating between ICU and HDU patients and
      identifying nursing skill requirements to care for the ICU and HDU patient
      groups.

PMID- 12008874
TI  - 'Giving each other energy'--harnessing valuable resources for clinical practice.

PMID- 12008875
TI  - Vulnerability and security in seriously ill patients in intensive care.
AB  - The purpose of this research was to gain an understanding of the experience of
      being a seriously ill patient in an intensive care unit (ICU). Fourteen former
      patients, aged 17-71 years old, who had been in ICU 3-53 days, participated in
      focus group interviews 3-6 months after discharge. The focus groups met 3 times
      each for 1.5 hours, resulting in 13-14 hours of audiotaped discussions. The
      transcribed data were qualitatively analysed to identify themes representing
      participants' experiences. Vulnerability emerged as a central concept that
      captured the identified themes. The data reveal that patient vulnerability while
      in ICU was related to extreme physical and emotional dependency. Lack of
      information and depersonalizing care were associated with fear, anxiety and
      increased vulnerability. Lack of sleep and rest also contributed to patient fear
      and anxiety. Vulnerability decreased when patients were kept informed of what was
      occurring while in ICU, received care that was personalized to their individual
      needs, and when their families were present. The results of this study suggest
      that ICU patients' vulnerability may be decreased by the security that they
      experience when they are adequately informed about what is happening, and when
      nursing and medical care is personalized to their individual needs.

PMID- 12008876
TI  - Peripherally inserted central catheters (PICCs): do they have a role in the care
      of the critically ill patient?
AB  - Over an eight-month period, 177 patients were admitted to a study to determine
      whether there was any significant difference between the peripherally inserted
      central catheter (PICC) in relation to the central venous catheter (CVC) and the
      peripheral venous access device in respect of the length of stay, incidence of
      phlebitis and the need for removal for suspected sepsis and infection. The
      results demonstrated no significant difference in terms of gender, age, or
      severity of illness. The PICC line had a significally higher length of stay and
      less incidence of phlebitis. In conclusion, PICC placement does have a place in
      the critical care setting. It should not be expected to replace existing methods
      of vascular access but used to provide a safe and effective alternative.

PMID- 12008877
TI  - Nursing research and nursing practice: an exploration of two different cultures.
AB  - Despite increasing efforts by both the government and the professions to
      institute evidence-based practice, there still remains a significant research
      practice gap in UK nursing. This paper explores the two worlds of practice and
      research and the factors that may affect them. It suggests that academic
      researchers and practitioners often have different perspectives and are working
      under different imperatives. These different cultures need to be recognized and
      made more explicit. Consideration will be given as to what sort of evidence is
      required by practitioners to nurse effectively, how we should identify this
      evidence and the role which research plays. The disharmony between the worlds of
      research and practice extends the discussion to consider the ways in which
      research is produced and disseminated. The question is raised as to why
      researchers fail to identify the contingencies, adaptations and social biases
      that affect their work. Strategies that might facilitate a franker discussion of
      research and the way in which it is produced will be illustrated by examples of
      research work undertaken by the author.

PMID- 12008878
TI  - Students' views on the assessment processes used in paediatric intensive care
      nursing courses.
AB  - This paper presents one element of the findings from a large study of paediatric
      intensive care nursing (PICN) education. The findings are discussed using a case
      study of one PICN course. The case study related to students' views on the
      assessment processes used, and the extent to which these were perceived to
      measure their skills and knowledge. The findings are not intended to be
      generalizable, but may give an indication of issues which should be considered in
      other courses. The study demonstrated that course members recognized the need for
      assessment of theory and practice, and for clear assessment criteria. However,
      they believed the assessment processes could themselves detract from their
      learning, and were not convinced that the assessment processes used accurately
      measured their skills and knowledge in relation to PICN practice. There was also
      a suggestion that practice assessments should be designed to measure competence
      in a more specific manner. In relation to the concept of self-assessment, there
      was some evidence that students would underassess their achievements using this
      approach.

PMID- 12008879
TI  - Glycoprotein IIb/IIIa inhibitors.
AB  - The GPIIb/IIIa inhibitors are potent anti-platelet agents with proven benefits in
      the treatment of patients with acute coronary syndromes and/or undergoing PCI.
      Assessment of the balance of risk and benefit needs to be undertaken in each
      individual case Consideration needs to be given to the economic impact of using
      these expensive drugs. There is much research activity in this rapidly evolving
      field and clinical experience is continually growing.

PMID- 12008880
TI  - Chest X-ray quiz. Atelectasis of the left lung.

PMID- 12008881
TI  - Doe's quality system program: cooperative development and implementation.
AB  - Implementation of a Quality Systems approach to making defensible environmental
      program decisions depends upon multiple, interrelated components. Often, these
      components are developed independently and implemented at various facility and
      program levels in an attempt to achieve consistency and cost savings. The U.S.
      Department of Energy, Office of Environmental Management (DOE-EM) focuses on
      three primary system components to achieve effective environmental data
      collection and use. (1) Quality System guidance, which establishes the management
      framework to plan, implement, and assess work performed; (2) A Standardized
      Statement of Work for analytical services, which defines data generation and
      reporting requirements consistent with user needs; and (3) A laboratory
      assessment program to evaluate adherence of work performed to defined needs,
      e.g., documentation and confidence. This paper describes how DOE-EM fulfills
      these requirements and realizes cost-savings through participation in interagency
      working groups and integration of system elements as they evolve.

PMID- 12008882
TI  - Iso 19011:2002--a combined auditing standard for quality and environmental
      management systems.
AB  - In a precedent-setting decision in 1998, the International Organization for
      Standardization (ISO) directed ISO Technical Committee (TC) 176 on Quality
      Management and ISO TC 207 on Environmental Management to develop jointly a single
      guideline standard for auditing quality and environmental management systems.
      When approved, this standard would replace ISO 10011-1, ISO 10011-2, and ISO
      10011-3 on quality auditing and ISO 14010, ISO 14011, and ISO 14012 on
      environmental auditing. A Joint Working Group (JWG) was established comprising
      experts from both TC 176 and TC 207 to develop the new standard, ISO 19011,
      Guidelines on Quality and/or Environmental Management Systems Auditing, and to
      incorporate lessons learned from efforts to improve compatibility between ISO
      9001/9004 and ISO 14001/14004, the standards for quality and environmental
      management systems, respectively. Work is proceeding on the development of ISO
      19011 with an expected completion in early 2002.

PMID- 12008883
TI  - Overview of executive order 13148: requirements for environmental management
      systems at federal facilities.
AB  - In April 2000, the White House issued Executive Order 13148, Greening the
      Government Through Leadership in Environmental Management. This Order applies to
      all appropriate federal facilities that have operations which interact with the
      environment and includes a number of environmentally-related requirements. The
      most significant requirement is that all appropriate federal facilities must
      implement an Environmental Management System (EMS) by December 31, 2005. This
      Order affects federal laboratories, testing facilities, maintenance facilities,
      hospitals, and so forth across all federal departments and agencies.

PMID- 12008884
TI  - Lessons learned in preparing method 29 filters for compliance testing audits.
AB  - Companies conducting compliance testing are required to analyze audit samples at
      the time they collect and analyze the stack samples if audit samples are
      available. Eastern Research Group (ERG) provides technical support to the EPA's
      Emission Measurements Center's Stationary Source Audit Program (SSAP) for
      developing, preparing, and distributing performance evaluation samples and audit
      materials. These audit samples are requested via the regulatory Agency and
      include spiked audit materials for EPA Method 29-Metals Emissions from Stationary
      Sources, as well as other methods. To provide appropriate audit materials to
      federal, state, tribal, and local governments, as well as agencies performing
      environmental activities and conducting emission compliance tests, ERG has
      recently performed testing of blank filter materials and preparation of spiked
      filters for EPA Method 29. For sampling stationary sources using an EPA Method 29
      sampling train, the use of filters without organic binders containing less than
      1.3 microg/in.2 of each of the metals to be measured is required. Risk Assessment
      testing imposes even stricter requirements for clean filter background levels.
      Three vendor sources of quartz fiber filters were evaluated for background
      contamination to ensure that audit samples would be prepared using filters with
      the lowest metal background levels. A procedure was developed to test new
      filters, and a cleaning procedure was evaluated to see if a greater level of
      cleanliness could be achieved using an acid rinse with new filters. Background
      levels for filters supplied by different vendors and within lots of filters from
      the same vendor showed a wide variation, confirmed through contact with several
      analytical laboratories that frequently perform EPA Method 29 analyses. It has
      been necessary to repeat more than one compliance test because of suspect metals
      background contamination levels. An acid cleaning step produced improvement in
      contamination level, but the difference was not significant for most of the
      Method 29 target metals. As a result of our studies, we conclude: Filters for
      Method 29 testing should be purchased in lots as large as possible. Testing firms
      should pre-screen new boxes and/or new lots of filters used for Method 29
      testing. Random analysis of three filters (top, middle, bottom of the box) from a
      new box of vendor filters before allowing them to be used in field tests is a
      prudent approach. A box of filters from a given vendor should be screened, and
      filters from this screened box should be used both for testing and as field
      blanks in each test scenario to provide the level of quality assurance required
      for stationary source testing.

PMID- 12008885
TI  - Improving the quality of data used in environmental economics research.
AB  - Valuing environmental goods through contingent valuation and through other survey
      techniques is difficult because of the lack of traditional markets for those
      goods. EPA provides leadership in overcoming these challenges, using focus
      groups, workshops, handbooks, and teams of distinguished economists to obtain
      more reliable economic data from the surveys. Agency economists have provided
      leadership in employing production economics tools to identify win-win approaches
      to solve pervasive and neglected environmental problems. In addition, we exploit
      the speed of sophisticated computers, building field runoff models into economic
      models and aggregating results from tens of thousands of field sites. These very
      flexible models provide much more credible, site-specific analyses than previous
      models, and they offer flexible and efficient remedies to support Total Maximum
      Daily Loads and other new programs.

PMID- 12008886
TI  - The radiochemist's role in the quality evaluation and assessment of radiological
      data in environmental decision making.
AB  - The quality evaluation and assessment of radiological data is the final step in
      the overall environmental data decisionprocess. This quality evaluation and
      assessment process is performed outside of the laboratory, and generally the
      radiochemist is not involved. However, with the laboratory quality management
      systems in place today, the data packages of radiochemical analyses are
      frequently much more complex than the project/program manager can effectively
      handle and additionally, with little involvement from radiochemists in this
      process, the potential for misinterpretation of radiological data is increasing.
      The quality evaluation and assessment of radiochemistry data consists of making
      three decisions for each sample and result, remembering that the laboratory
      reports all the data for each analyses as well as the uncertainty in each of
      these analyses. Therefore, at the data evaluation and assessment stage, the
      decisions are: (1) is the radionuclide of concern detected (each data point
      always has a number associated with it?); (2) is the uncertainty associated with
      the result greater than would normally be expected; and (3) if the laboratory
      rejected the analyses is there serious consequences to other samples in the same
      group? The need for the radiochemist's expertise for this process is clear.
      Quality evaluation and assessment requires the input of the radiochemist
      particularly in radiochemistry because of the lack of redundancy in the
      analytical data. This paper describes the role of the radiochemist in the quality
      assessment of radiochemical data for environmental decision making.

PMID- 12008887
TI  - The role of field auditing in environmental quality assurance management.
AB  - Environmental data quality improvement continues to focus on analytical
      laboratoryperformance with little, if any, attention given to improving the
      performance of field consultants responsible for sample collection. Many
      environmental professionals often assume that the primary opportunity for data
      error lies within the activities conducted by the laboratory. Experience in the
      evaluation of environmental data and project-wide quality assurance programs
      indicates that an often-ignored factor affecting environmental data quality is
      the manner in which a sample is acquired and handled in the field. If a sample is
      not properly collected, preserved, stored, and transported in the field, even the
      best laboratory practices and analytical methods cannot deliver accurate and
      reliable data (i.e., bad data in equals bad data out). Poor quality environmental
      data may result in inappropriate decisions regarding site characterization and
      remedial action. Field auditing is becoming an often-employed technique for
      examining the performance of the environmental sampling field team and how their
      performance may affect data quality. The field audits typically focus on: (1)
      verifying that field consultants adhere to project control documents (e.g., Work
      Plans and Standard Operating Procedures [SOPs]) during field operations; (2)
      providing third-party independent assurance that field procedures, quality
      assurance/ quality control (QA/QC)protocol, and field documentation are
      sufficient to produce data of satisfactory quality; (3) providing a defense in
      the event that field procedures are called into question; and (4) identifying
      ways to reduce sampling costs. Field audits are typically most effective when
      performed on a surprise basis; that is, the sampling contractor may be aware that
      a field audit will be conducted during some phase of sampling activities but is
      not informed of the specific day(s) that the audit will be conducted. The audit
      also should be conducted early on in the sampling program such that deficiencies
      noted during the audit can be addressed before the majority of field activities
      have been completed. A second audit should be performed as a follow-up to confirm
      that the recommended changes have been implemented. A field auditor is assigned
      to the project by matching, as closely as possible, the auditor's experience with
      the type of field activities being conducted. The auditor uses a project-specific
      field audit checklist developed from key information contained in project control
      documents. Completion of the extensive audit checklist during the audit focuses
      the auditor on evaluating each aspect of field activities being performed. Rather
      than examine field team performance after sampling, a field auditor can do so
      while the samples are being collected and can apply real-time corrective action
      as appropriate. As a result of field audits, responsible parties often observe
      vast improvements in their consultant's field procedures and, consequently,
      receive more reliable and representative field data at a lower cost. The cost
      savings and improved data quality that result from properly completed field
      audits make the field auditing process both cost-effective and functional.

PMID- 12008888
TI  - Data standards are back seat drivers! Methodology for incorporating information
      quality into quality assurance project plans.
AB  - Quality assurance project plans for environmental data collections consider user
      requirements for the measurements and express these in the form of data quality
      objectives. User requirements now may include capture of measurements and
      associated information in prescribed formats to facilitate entry into
      computerized information systems. Establishing ahead of time that the data
      requirements may be an important "back seat driver" for an environmental
      collection effort can save considerable resources for an organization. Also, the
      planning may need to accommodate unique requirements associated with the entry of
      data into data collection systems.

PMID- 12008889
TI  - The quality management system as a tool for improving stakeholder confidence.
AB  - The Corps of Engineers works with local restoration advisory boards (RAB) to
      exchange information and develop plans for restoration of closed military bases
      for civilian reuse. Meetings of the RAB to discuss progress in environmental
      assessment and restoration of former defense sites can be contentious due to the
      complex technical nature of the information to be shared and the personal stake
      that the members of the community have in ensuring that contentious areas are
      restored for safe use. A prime concern of community representatives is often the
      quality of the data used to make environmental decisions. Laboratory case
      narratives and data flags may suggest laboratory errors and low data quality to
      those without an understanding of the information's full meaning. RAB members
      include representatives from local, state, and tribal governments, the Department
      of Defense, the Environmental Protection Agency, and the local community. The
      Corps of Engineers representatives usually include project technical and
      management personnel, but these individuals may not have sufficient expertise in
      the project quality assurance components and laboratory data quality procedures
      to completely satisfy community concerns about data quality. Communication of
      this information to the RAB by a quality assurance professional could serve to
      resolve some of the questions members have about the quality of acquired data and
      proper use of analytical results, and increase community trust that appropriate
      decisions are made regarding restoration. Details of the effectiveness of
      including a quality assurance professional in RAB discussions of laboratory data
      quality and project quality management are provided in this paper.

PMID- 12008890
TI  - Using field data analysis for environmental decision making and subsequent
      remediation at two example sites.
AB  - One of the major challenges in remediating contaminated sites is having quick
      access to quality data on which to base remedial decisions as onsite work
      progresses. Case studies are presented at two Superfund sites where field
      screening and field analyses are used to provide these data. Emphasis is placed
      on the importance of high quality field data, as these data are the basis for
      remedial decisions prior to receipt of offsite laboratory confirmation. The
      decision-making processes for remediating contaminated soils and structures are
      presented in addition to project specifics including data quality objectives,
      field data collection procedures, quality assurance/quality control procedures,
      and comparisons of the field data with offsite laboratory results.

PMID- 12008891
TI  - Two data bases in every garage: information quality systems.
AB  - Enterprises, including Federal agencies such as the U.S. Environmental Protection
      Agency (EPA), are now identifying their information as a strategic resource. As
      part of a new strategy, enterprises address quality system planning. This
      technical paper presents some of EPA's approaches and techniques for reconciling
      quality system considerations for science and technical activities with quality
      system considerations for information technology and resources. Identification of
      key information quality indicators, management processes, and assessment
      processes are addressed.

PMID- 12008892
TI  - How good are my data?: Information quality assessment methodology.
AB  - Quality assurance techniques used in software development and hardware
      maintenance/reliability help ensure that data in a computerized information
      management system are maintained well. However, information workers may not know
      the quality of data resident in their information systems. Knowledge of the
      quality of information and data in an enterprise provides managers with important
      facts for managing and improving the processes that impact information quality.
      This paper presents quality assessment methodology to assist information workers
      in planning and implementing an effective assessment of their information data
      and quality. The areas covered include: identifying appropriate information
      quality indicators; developing assessment procedures; conducting information
      quality assessments; reporting information assessment results; tracking
      improvements in information quality.

PMID- 12008893
TI  - Raising the curtain on the gray region.
AB  - The gray region in EPA Document QA/G-4 is defined as the range of possible
      parameter values near the action level where the cost of determining that the
      alternative condition is true outweighs the expected consequences of a decision
      error. The gray region is also described as a range of true parameter values
      within the alternative condition near the action level where it is "too close to
      call." EPA Document QA/G-4HW states that during the planning stage the action
      level is based on an ideal decision rule, while during the assessment stage an
      operational decision rule is used. This paper analyzes the factors that define
      the gray region and the action level, including the errors of the first kind (a)
      and second kind (beta) and the number of samples taken to determine the mean
      result. The relationship between the Decision Performance Curve presented in EPA
      QA/G-4 and the statistical power curve is also discussed. The statistically
      derived critical level is identified as the concentration of importance for
      decision-making. The action level is defined in terms of the critical level so
      that its value is consistent for decisions made during both planning (a priori
      decisions) and assessment (a posteriori decisions).

PMID- 12008894
TI  - LINEs and gypsy-like retrotransposons in Hordeum species.
AB  - LINE and gypsy-like retroelements were studied in the genome of Hordeum vulgare,
      and compared with the representatives of the major sections of the genus Hordeum.
      We isolated reverse transcriptase (RT) genes from four gypsy-like and three LINE
      families using PCR primers specific for the corresponding conserved domains. A
      full-length barley LINE of 6295 bp, named BLIN, was isolated from a BAC genomic
      library. BLIN looks alien in the barley genome because its G+C content is 62%
      compared to an average of 45%. The BLIN nucleotide sequence showed it was
      structurally intact with the features typical of non-LTR retrotransposons,
      including 16 bp target site duplications, two short cysteine motifs, and two
      degenerate open reading frames (ORFs). The high degeneracy was also found in RT
      domain of both gypsy-like and, particularly, LINE families. The copy numbers of
      the gypsy-like families were relatively low compared to well-characterized copia
      like element BARE-1. Each gypsy-like family gave unique RFLP patterns when
      hybridized to genomic DNA from each of the four basic Hordeum genomes. H. vulgare
      (I genome) had accumulated more copies than the wild Hordeum species (H, X, Y
      genomes), with the other I genome species, H. bulbosum, being intermediate.
      Analysis of the BAC library and in situ hybridization with LINE RT domains showed
      the low copy number of the LINE families, but there was little correlation
      between hybridization patterns and the division of the genus into four basic
      genomes. The distribution and content of gypsy retrotransposons in the BAC
      library indicated that a few copies are nested, although most are present as
      single, distinct, copies. Our results suggest that the major groups of
      retroelements make individual contributions to the shape of the plant genome; the
      factors involved in their amplification and distribution are independent, also
      varying among species.

PMID- 12008895
TI  - The Slr0924 protein of Synechocystis sp. strain PCC 6803 resembles a subunit of
      the chloroplast protein import complex and is mainly localized in the thylakoid
      lumen.
AB  - An isolated 25 kDa protein of Synechocystis sp. PCC 6803 was N-terminally
      sequenced and assigned to a protein encoded by the ORF slr0924. This ORF shows a
      certain degree of sequence similarity to a subunit from the protein Translocon at
      the Inner envelope of pea Chloroplasts (Tic22). The deduced amino acid sequence
      of Slr0924 has a N-terminal extension, that contains two possible translational
      start points and two possible cleavage sites for leader peptidases.
      Immunostaining with an antibody raised to the over-produced protein revealed two
      cross-reacting forms, which probably correspond to a larger intermediate and the
      mature protein. Immunogold labelling of thin sections showed that the protein is
      located mainly in the thylakoid region. This result was verified by thylakoid
      membrane fractionation indicating that Slr0924 is a lumenal protein. The slr0924
      gene product is essential for the viability of Synechocystis sp. PCC 6803 as
      shown by interposon mutagenesis. The merodiploid strain showed reduced
      photosynthetic activity compared to the wild-type. Furthermore, growth of the
      merodiploid strain was found to be completely inhibited after cultivation with
      glucose. Accordingly, the amount of the slr0924 gene product was regulated by
      glucose and light intensities in wild-type cells. The potential function of the
      protein in Synechocystis sp. PCC 6803 will be discussed.

PMID- 12008896
TI  - Gene expression studies on developing kernels of maize sucrose synthase (SuSy)
      mutants show evidence for a third SuSy gene.
AB  - Previous studies have identified two tissue- and cell-specific, yet functionally
      redundant, sucrose synthase (SuSy) genes, Sh1 and Sus1, which encode
      biochemically similar isozymes, SH1 and SUS1 (previously referred to as SS1 and
      SS2, respectively). Here we report evidence for a third SuSy gene in maize, Sus3,
      which is more similar to dicot than to monocot SuSys. RNA and/or protein blot
      analyses on developing kernels and other tissues show evidence of expression of
      Sus3, although at the lowest steady-state levels of the three SuSy gene products
      and without a unique pattern of tissue specificity. Immunoblots of sh1sus1-1
      embryos that are either lacking or deficient for the embryo-specific SUS1 protein
      have shown a protein band which we attribute to the Sus3 gene, and may contribute
      to the residual enzyme activity seen in embryos of the double mutant. We also
      studied developing seeds of the double mutant sh1sus1-1, which is missing 99.5%
      of SuSy enzyme activity, for evidence of co-regulation of several genes of sugar
      metabolism. We found a significant reduction in the steady-state levels of
      Miniature-1 encoded cell wall invertase2, and Sucrose transporter (Sut) mRNAs in
      the double mutant, relative to the lineage-related sh1Sus1 and sh1Sus1 kernels.
      Down-regulation of the Mn1 gene was also reflected in significant reductions in
      cell wall invertase activity. Co-regulatory changes were not seen in the
      expression of Sucrose phosphate synthase, UDP-glucose pyrophosphorylase, and ADP
      glucose pyrophosphorylase.

PMID- 12008897
TI  - Identification of SnIP1, a novel protein that interacts with SNF1-related protein
      kinase (SnRK1).
AB  - Plant SNF1-related protein kinase (SnRK1) phosphorylates 3-hydroxy-3
      methylglutaryl-Coenzyme A, nitrate reductase and sucrose phosphate synthase in
      vitro, and is required for expression of sucrose synthase in potato tubers and
      excised leaves. In this study, a barley (Hordeum vulgare) endosperm cDNA, SnIP1,
      was isolated by two-hybrid screening with barley SnRK1b, a seed-specific form of
      SnRK1. The protein encoded by the SnIP1 cDNA was found to interact with barley
      SnRK1b protein in vitro. Southern analysis suggested that barley contains a
      single SnIP1 gene or small gene family. SnIP1 transcripts were detected in RNA
      isolated from leaf, root and mid-maturation seed. Sequence similarity searches
      against protein, nucleotide and expressed sequence tag databases identified
      hitherto uncharacterized sequences related to SnIP1 from maize (Zea mays,
      accession number AI691404), arabidopsis (Arabidopsis thaliana. AC079673 and
      AB016886) and poplar (Populus balsamifera, AI166543). No homologous sequences
      were identified from outside the plant kingdom, but weak sequence similarity was
      found between the SnIP1 peptide and yeast (Saccharomyces cerevisiae) SNF4 and its
      mammalian homologue AMPKy. Nevertheless, SnIP1 failed to complement a yeast snf4
      mutant. SnIP1 was found to have little overall sequence similarity with the PV42
      family of SNF4-like plant proteins, but proteins of both the SnIP1 and PV42
      families contain a conserved hydrophobic sequence we named the SnIP motif.

PMID- 12008898
TI  - Matrix attachment regions (MARs) enhance transformation frequencies and reduce
      variance of transgene expression in barley.
AB  - Nuclear matrix attachment regions (MARs) are defined as genomic DNA sequences,
      located at the physical boundaries of chromatin loops. They are suggested to play
      a role in the cis unfolding and folding of the chromatin fibre associated with
      the regulation of gene transcription. Inclusion of MARs in transgene cassettes
      enhances their expression and reduces position-effect variations in the
      transgenic host. The present study is the first to investigate the influence of
      MAR sequences on transformation frequencies and transgene expression in barley,
      which is highly relevant to the future improvement of this crop by biotechnology.
      Two plant MAR sequences were tested both for their ability to bind to the nuclear
      matrix of barley leaf nuclei and to regulate the expression of a reporter gene in
      transgenic barley. Competitive in vitro MAR binding assays with the 520 bp P1-MAR
      from soybean and the 516 bp TBS-MAR from petunia revealed that only the P1-MAR
      had specific binding affinity for barley nuclear matrices. The barley
      transformation frequency with the uidA reporter gene was increased 2-fold when
      the gene was flanked with either the P1-MAR or TBS-MAR, while the gene copy
      number was strongly reduced. The presence of P1-MAR sequences increased the mean
      activity and reduced the variance in expression of a co-integrated reporter gene
      in barley consistent with the proposed model of MAR activity.

PMID- 12008899
TI  - Nuclear identity specifies transcriptional initiation in plant mitochondria.
AB  - Alterations in mitochondrial gene expression and abnormal floral phenotypes, such
      as male sterility, characterize alloplasmic plants having the nucleus from
      Nicotiana tabacum combined with the cytoplasm from Nicotiana repanda. In all
      Nicotiana species investigated the mitochondrial atpl gene is co-transcribed with
      the upstream orf274; however, unique for alloplasmic plants is a marked
      accumulation of these mitochondrial co-transcripts. In the present work, we show
      that a major component of the transcript difference is that in the alloplasmic
      male-sterile plants transcription initiates from novel sites internal to orf274.
      The sequences surrounding these initiation sites lack the CRTA consensus motif
      for plant mitochondrial promoters as well as similarity to other known plant
      mitochondrial promoters. Thus, initiation of transcription is under control of a
      mitochondrial promoter of a novel non-consensus type. This non-consensus promoter
      is inactivated when the fertility restoring heritable fragment chromosome from N.
      repanda is present in the N. tabacum nucleus of the alloplasmic plants. Our data
      suggest that the fertility-restoring fragment chromosome encodes a factor that
      represses initiation from this unusual promoter.

PMID- 12008900
TI  - Cloning by pathway activation in yeast: identification of an Arabidopsis thaliana
      F-box protein that can turn on glucose repression.
AB  - We describe a method for identifying signal transducing proteins from other
      organisms by their ability to turn on a signalling pathway when they are
      expressed at high level in yeast. The method was tested on a cDNA library from
      Arabidopsis thaliana, which was screened for clones that can activate glucose
      repression in the absence of glucose. Six clones were characterized. One of them
      codes for AtGRH1, a new F-box protein that shows similarity to GRR1, a yeast
      protein involved in glucose repression. The ability of AtGRHI to activate glucose
      repression is dependent on the MIG1 repressor. Two-hybrid experiments revealed
      that AtGRH1 can interact with AtSKP1a and AtSKP1b, two recently identified SKP1
      homologues in Arabidopsis. Other clones identified in the screen encode the
      transcription factor AtEBP, the 14-3-3 protein AtGF14 and two new proteins:
      AtMYR1 and AtPOZ1. None of these proteins turn on glucose repression. Instead,
      they illustrate various other ways by which foreign proteins can interfere with
      expression of a yeast gene. We conclude that our method worked as expected in at
      least one case, and that it could be applied to other signalling pathways that
      are conserved between yeast and higher eukaryotes.

PMID- 12008901
TI  - Symbiotic and non-symbiotic expression of cgMT1, a metallothionein-like gene from
      the actinorhizal tree Casuarina glauca.
AB  - A clone for a type 1 metallothionein (cgMT1) was isolated from a Casuarina glauca
      nodule cDNA library. The corresponding gene belongs to a small family and is
      highly expressed in roots and nitrogen-fixing nodules, whereas low expression was
      observed in aerial parts of the plant. The promoter region of cgMT1 was isolated
      and fused to the beta-glucuronidase (gus) gene. Transgenic Casuarinaceae plants
      showed that the cgMT1 promoter was most active in roots and in the oldest region
      of the shoot. In situ hybridization indicated that in nodules cgMT1 transcript is
      present in mature Frankia-infected cells and in the pericycle. Possible roles for
      cgMT1 in symbiotic and nonsymbiotic tissues are discussed.

PMID- 12008902
TI  - Harlequin (hlq) and short blue root (sbr), two Arabidopsis mutants that
      ectopically express an abscisic acid- and auxin-inducible transgenic carrot
      promoter and have pleiotropic effects on morphogenesis.
AB  - Plant growth and development is regulated by complex interactions among different
      hormonal, developmental and environmental signalling pathways. Isolation of
      mutants in these processes is a powerful approach to dissect unknown mechanisms
      in regulatory networks. The plant hormones abscisic acid (ABA) and auxin are
      involved in vegetative, developmental and environmental growth responses,
      including cell division and elongation, vascular tissue differentiation and
      stress adaptation. The uidA (beta-glucuronidase; GUS) reporter gene driven by the
      carrot (Daucus carota) late embryogenesis-abundantDc3 promoter in transgenic
      Arabidopsis thaliana seedlings is ABA-inducible in the root zone of elongation
      and vasculature. We show here that the ABA-insensitive2-1 mutation (abi2) reduces
      ABA-inducible Dc3-GUS expression in these root tissues. Dc3-GUS expression is
      also induced in root cortex cells by indole-3-acetic acid. We mutagenized, with
      ethyl methane sulfonate, 5100 M1 abi2/abi2 homozygous plants of a line that
      carries two independent Dc3-GUS reporter genes and screened M2 clonal lines for
      ABA-inducible Dc3-GUS expression in roots. We isolated two novel single-gene
      nuclear mutants, harlequin (hlq) and short blue root (sbr), that ectopically
      express Dc3-GUS in roots and have pleiotropic effects on morphogenesis. The hlq
      mutant expresses Dc3-GUS in a checkered pattern in epidermis of roots and
      hypocotyls, accumulates callose and has deformed and collapsed epidermal cells
      and abnormal and reduced root hairs and leaf trichomes. It (hlq) is also dwarfed,
      skotomorphogenic and sterile. The sbr mutant is a seedling-lethal dwarf that over
      expresses Dc3-GUS in the root and has radially swollen epidermal cells in the
      root and hypocotyl, supernumerary cell number in the root cortex and epidermis,
      abnormal vasculature, and abnormal epidermal cell patterning in cotyledons and
      leaves. It (sbr) also exhibits a semidominant root phenotype of reduced growth
      and lateral root initiation. The hlq and sbr mutants are not rescued by exogenous
      application of plant growth regulators. The hlq and sbr mutants do not require
      the abi2-1 mutant gene for their phenotypes and map to chromosome III and I,
      respectively. Further characterization of the hlq and sbr phenotypes and genes
      may provide insights into the relationship of hormone- and stress-regulated gene
      expression to morphogenesis and plant growth.

PMID- 12008903
TI  - Assessing outcome in community mental health patients: a comparative analysis of
      measures.
AB  - BACKGROUND: We undertook a twelve-month intervention study for community mental
      health patients using a number of measures administered at baseline and at twelve
      months. Overall improvement in that sample allowed for comparative analyses of
      the key measures in terms of their ability to measure and to predict outcome.
      AIMS: To assess and compare the usefulness of each of the measures in predicting
      outcome status. METHODS: A patient-rated quality of life (QOL) questionnaire, the
      DSM-III-R Global Assessment of Functioning (GAF), the Life Skills Profile (LSP)
      and the Health of the Nation Outcome Scales (HoNOS) were compared and evaluated
      in a sample of seventy-nine patients. RESULTS: The LSP appeared to measure
      disability only, while the HoNOS and the GAF assessed composite symptoms and
      general functioning. The HoNOS was identified as the most distinctive predictor
      of outcome. CONCLUSIONS: The utility of the HoNOS as an overall service measure
      is supported, while properties and likely utility of other measures in outcome
      studies are detailed.

PMID- 12008904
TI  - Symptoms of obsessive-compulsive disorder in a sample of Iranian patients.
AB  - BACKGROUND: Characteristic features of the obsessive-compulsive disorder (OCD)
      occur with remarkable consistency in different cultural settings. The content of
      symptoms, however, seems to vary across cultures. AIMS: To examine the content of
      symptoms in a sample of OCD patients from Iran. METHODS: In a sample of 135
      patients recruited from three treatment settings the prevalence of symptoms with
      different contents were ranked and compared across genders. RESULTS: Doubts and
      indecisiveness were the most common obsessions and washing the most common
      compulsion for the whole sample. Fears of impurity and contamination, obsessive
      thoughts about self-impurity and washing compulsions were more common in women,
      whereas blasphemous thoughts and orderliness compulsions were more common in men.
      CONCLUSIONS: With minor differences, the pattern of symptoms with various
      contents in this sample was similar to that in Western settings.

PMID- 12008905
TI  - Mental illness in one district of Uganda.
AB  - AIMS: To estimate the prevalence of psychiatric disorder in one district of
      Uganda. METHODS: Data were collected from a survey of a random sample of
      households in Kabarole, West Uganda. Interviews were carried out with household
      members. Further information was obtained from interviews of key community
      informants and from Focus Group discussions conducted in each Parish. RESULTS:
      Some 384 households were surveyed. Of these, 99 households identified members
      with a mental illness in the previous year and a total of 130 individuals were
      identified, 12 of whom were children. Few individuals had been seen by formal
      mental health services and traditional methods of treatment were commonly used.
      CONCLUSIONS: The estimated prevalence of 30.7% in adults is higher than that of
      25.3% found in the only other community based survey of mental illness previously
      conducted in Uganda. A well conducted study using modern case defining methods
      needs to be carried out in Uganda.

PMID- 12008906
TI  - Evaluating the use of a psychiatric intensive care unit: is ethnicity a risk
      factor for admission?
AB  - OBJECTIVE: This paper presents a descriptive study, undertaken in 1993, of a
      Psychiatric Intensive Care Unit (PICU) serving a deprived inner-city area,
      investigating the role of ethnicity as a risk factor for admission to the unit.
      METHODS: Clinical and demographic data were collected on consecutive admissions
      to a PICU. Global Assessment of Function Scale scores were rated on admission and
      at discharge from the unit. RESULTS: The majority of patients were male (63%) and
      the commonest DSM-IV diagnoses were schizophrenia (42%) and bipolar affective
      disorder (24%). Average length of stay was 13 days with patients making
      significant improvement in functioning during their stay. Fifty-five percent of
      PICU admissions came from ethnic minorities (compared with 25.6% of total
      hospital admissions and 20.9% of the local catchment area population aged between
      16 and 65 years). There was no evidence that ethnic minority patients were being
      inappropriately admitted to the PICU. CONCLUSIONS: It is likely that a variety of
      factors contributed to the high rate of PICU admission amongst ethnic minority
      patients, including an increased prevalence of major mental illness and more
      frequent cannabis abuse.

PMID- 12008907
TI  - The goals and method of the Andalusian Case Register for Schizophrenia.
AB  - BACKGROUND: Psychiatric case registers have been acknowledged as a valuable
      source of data, a long time ago. However, a growing interest exists in data on
      service utilization by patients belonging to groups with a related diagnosis to
      enable adequate planning of health resources. AIMS: The aims of the Andalusian
      Case Register for Schizophrenia are to determine the prevalence of schizophrenia
      of those cared for by the public network of mental health services and to
      describe their pattern of care. METHODS: Cases included on the Register are those
      persons resident in South Granada area with a diagnosis of schizophrenia and
      related disorders. The agencies which sent the information to the Register are
      all the mental health facilities in the catchment area. CONCLUSIONS: The Register
      is a flexible instrument to use for epidemiological research and mental health
      care planning.

PMID- 12008908
TI  - Quality of life and other characteristics of Viennese mental health care users.
AB  - BACKGROUND: The purposes of this study are (1) to characterise patients with
      different treatment experiences, (2) to evaluate differences in quality of life
      (QoL) among patients with different treatment experiences, (3) to evaluate
      changes in QoL following community resettlement, and (4) to find predictors of
      overall life satisfaction (OLS). METHODS: Treatment experiences are defined
      according to service use as follows: (a) user of in- and outpatient services
      (overall users), (b) user of inpatient (inpatients) or (c) outpatient facilities
      only (outpatients). Demographic and clinical data of 425 psychiatric patients are
      analysed cross-sectionally in relation to their treatment experiences. QoL of
      former inpatients is followed up after hospital discharge. RESULTS: Long-term
      'overall users' have a significantly higher QoL than long-term 'outpatients' or
      'inpatients'. QoL of former inpatients increases after discharge. Predictors of
      higher OLS are high income, high subjective social functioning (SFQ), good self
      rated health, satisfactory QoL domains as well as being single or cohabiting,
      diagnosis of schizophrenia, 'outpatients', and 'overall users'. Together they
      explain 63% of the variance in patients' subjective OLS. CONCLUSION: QoL is
      independent of illness severity. Deinstitutionalisation improves QoL and OLS is
      mainly predicted by subjective variables.

PMID- 12008909
TI  - Dangerous severe personality disorder--bad tidings from the UK.

PMID- 12008910
TI  - Pharmacoepidemiological patterns of antidepressant prescribing in primary care in
      rural Spain (1995-1999).
AB  - BACKGROUND: The prescribing of psychoactive drugs is increasing progressively in
      western countries. The new psychiatric care modalities, in contact with the
      primary care centres and closer to the population, might be determining this
      increase in a major way. METHODS: Official data of prescription were collected
      from the Public Primary Care Department of Pharmacy, to monitor the use of
      antidepressants during a five year period in a rural health area (140,359
      inhabitants). Daily defined dosage (DDD) was used as the measuring unit. RESULTS
      AND CONCLUSIONS: The total use of antidepressants increased progressively during
      the period studied from 10.47 DDD/1000 inhabitants/day in 1995 to 18.50 in 1999
      (an increase of 77.08%). The majority of this increase is explained by the
      greater use of SSRIs for which prescribing multiplied by 2.5. It is significant
      that the figure for the use of tricyclics has not fallen parallel to the increase
      of SSRIs. General practitioners might be losing their fear of diagnosing and
      treating mood disorders. Probably a pool of patients is included who were not
      receiving the correct treatment a few years ago, but to what level are we going
      to lower the symptomatic threshold for prescribing antidepressants?

PMID- 12008911
TI  - Editorial--alliances against malaria in Africa.

PMID- 12008912
TI  - Zentralblatt fur Bakteriologie - 100 years ago: the debate on the causative role
      of "spindle-shaped" bacteria and "spirilla" in infectious diseases.

PMID- 12008913
TI  - Delivery of dangerous goods: type III secretion in enteric pathogens.
AB  - Type III secretion systems (TTSSs) of Gram-negative pathogens are molecular
      syringes that inject bacterial virulence factors directly into host cells. These
      virulence factors manipulate host cell pathways to aid bacterial survival within
      the host. Four important enteric pathogens use TTSSs to colonize and persist
      within the intestinal environment. The following is a brief review of the way in
      which TTSSs and their effectors contribute to the pathogenic nature of the
      prototypic diarrheal pathogens Salmonella, Shigella, Yersinia and
      enteropathogenic Escherichia coli (EPEC).

PMID- 12008914
TI  - The role of motility as a virulence factor in bacteria.
AB  - Many bacteria that cause diseases of humans, animals and plants use flagella to
      move. This review summarises recent studies that have analysed the role of
      motility and chemotaxis in the host-parasite relationship of pathogenic bacteria.
      These studies have shown that for many pathogens, motility is essential in some
      phases of their life cycle and that virulence and motility are often intimately
      linked by complex regulatory networks. Possibilities to exploit bacterial
      motility as a specific therapeutic antibacterial target to cure or prevent
      disease are discussed.

PMID- 12008915
TI  - Various bacterial pathogens and symbionts infect the amoeba Dictyostelium
      discoideum.
AB  - The haploid soil amoeba Dictyostelium discoideum is a suitable model organism to
      study host-pathogen interactions with Legionella pneumophila. In this study we
      show that D. discoideum AX2 is also susceptible to infection with other important
      human pathogens and obligate intracellular symbionts. Infection assays
      demonstrated that Legionella-like amoebal pathogens (LLAP K62), Mycobacterium
      avium and the obligate intracellular endosymbionts of Acanthamoeba sp. strains
      TUME1, UWE25 and UWC6 were able to multiply within Dictyostelium. Salmonella
      typhimurium and Pseudomonas aeruginosa also invaded Dictyostelium, however were
      degraded shortly after uptake. Comitin-minus host cells were more permissive to
      infections with L. pneumophila and LLAP K62. Furthermore, this mutation
      significantly delayed the degradation of S. typhimurium. Accompanying electron
      and fluorescence microscopy of infected AX2 cells revealed that L. pneumophila
      and M. avium replicate within vacuoles, while LLAP K62, TUME1 and UWE25 were
      tightly enclosed by membranous structures within the cytoplasm. The beta
      proteobacterium UWC6 was found to persist in the cytoplasm. The observed
      subcellular locations which correspond to the locations within the respective
      natural hosts suggest that D. discoideum is a representative model system for
      these pathogens and symbionts.

PMID- 12008916
TI  - The bacteriophage-associated ehly1 and ehly2 determinants from Escherichia coli
      O26:H- strains do not encode enterohemolysins per se but cause release of the
      ClyA cytolysin.
AB  - This report presents evidence that the bacteriophage-associated proteins Ehlyl
      and Ehly2 (enterohemolysin) of non-verotoxigenic E. coli O26:H- are not
      hemolysins per se. Ehly1 and Ehly2 conferred a hemolytic phenotype on wild-type
      but not on clyA knockout strains of E. coli K-12 when introduced in trans on
      plasmids. According to immunoblot analyses, and studies of the expression from a
      chromosomal clyA::luxAB fusion, the production of cytolysin A (ClyA) was not
      enhanced by the expression of Ehly1 or Ehly2. However, the analysis provided
      evidence that there was a low basal level expression of ClyA by E. coli K-12
      strains that could be detected phenotypically when the bacteria were subject to
      lytic effects by bacteriophages or their gene products. In experiments when lysis
      of the bacteria was caused deliberately either by using lytic bacteriophages (P1
      or phiW), or by triggering the SOS response with mitomycin C treatment,
      sufficient amounts of ClyA were released to cause detectable lysis on blood agar
      plates. Taken together, our findings support a model where Ehlyl and Ehly2 cause
      a hemolyric phenotype on blood agar as a result of their lytic and lethal effects
      on the bacterial hosts.

PMID- 12008917
TI  - Temperate phages in Salmonella enterica serovar Typhimurium: implications for
      epidemiology.
AB  - Salmonella enterica serovar Typhimurium is the most common Salmonella serovar
      isolated from humans in Australia. The most common definitive phage types (DT)
      include 9, 64 and 135. Induction of lysogenic phages from DT 64 with mitomycin C
      followed by cesium chloride gradient purification, resulted in separation of two
      populations of phage particles. DNA extracted from these particles that was
      digested with SmaI showed two distinct patterns of banding. Transmission electron
      microscopy showed that both phage particles belong to the podovirus family of the
      C1 morphotype. One of the phages, ST64T is capable of mediating both generalized
      transduction and bacteriophage type conversion. Crude phage lysate induced from
      S. Typhimurium DT 64 was capable of phage type conversion. S. Typhimurium DT 9
      was converted to DT 64 and DT 135 was converted to DT 16. S. Typhimurium DT 41
      was also converted to DT 29. Amplified-fragment length polymorphism revealed
      differences between the original isolates and the convertants. Phage type
      conversion raises the question of the stability of the bacterial phage types in
      natural settings and the possibility of its occurrence during an outbreak
      scenario.

PMID- 12008918
TI  - Modified pulsed-field gel electrophoresis method for DNA degradation-sensitive
      Salmonella enterica and Escherichia coli strains.
AB  - A number of S. enterica and E. coli strains appeared sensitive to a rapid DNA
      degradation during the course of PFGE pattern analysis. This kind of DNA
      degradation could not be stopped by intensive treatment with proteinase K,
      formalin treatment, or other modifications of the protocol for the isolation of
      intact chromosomal DNA. However, the application of 100 microM thiourea into the
      running buffer gave rise to clear-cut PFGE patterns and in turn to an overall
      typeability.

PMID- 12008919
TI  - Cloning and sequencing of Enterobacter aerogenes OmpC-type osmoporin linked to
      carbapenem resistance.
AB  - Using outbreak-related strains of Enterobacter aerogenes, we cloned and sequenced
      ompK39, the structural gene coding for outer membrane protein OmpK39. Its lack of
      expression was closely associated with a phenotype exhibiting low-level
      carbapenem resistance. Detailed alignment of the predicted amino acid sequence
      revealed that OmpK39 is a member of the OmpC subclass of enterobacterial porins,
      with the highest degree of homology to Klebsiella pneumoniae OmpK36. Based on a
      computerized alignment including Escherichia coli PhoE and OmpF, the 3D
      structures of which are known from X-ray studies, OmpK39 can be assumed to form
      the typical beta-barrel structure which is common to all enterobacterial porins.
      Since no inhibitory DNA sequences could be detected in ompk39 in the resistant
      strains, porin deficiency leading to carbapenem resistance seems to involve
      alterations in key regulatory genes and/or the promotor sequence rather than a
      direct mutation in the structural gene.

PMID- 12008920
TI  - Antifungal properties of 5-hydroxytryptamine (serotonin) against Aspergillus spp.
      in vitro.
AB  - This study shows that 5-hydroxytrypatmine (5-HT, serotonin) is fungicidal towards
      conidia and hyphae of clinical isolates of Aspergillus (A.) fumigatus, A. flavus
      and A. terreus. The minimal fungicidal concentrations for Aspergillus conidia and
      hyphae ranged between 14.68 to 117.5 mM and 29.37 to 235 mM during 24 and 48 h of
      incubation. Several serotonin receptor antagonists (5-HT2, 5-HT3) studied in
      vitro did not influence antifungal activity.

PMID- 12008921
TI  - The morbillivirus receptor SLAM (CD150).
AB  - Morbilliviruses are highly contagious pathogens that cause some of the most
      devastating viral diseases of humans and animals, including measles virus (MV),
      canine distemper virus (CDV), and rinderpest virus (RPV). They replicate mainly
      in lymphoid organs throughout the body and cause severe immunosuppression
      accompanied with lymphopenia. We have recently shown that human, canine, and
      bovine signaling lymphocyte activation molecules (SLAMs; also known as CD150) act
      as cellular receptors for MV, CDV, and RPV, respectively. In these three
      morbilliviruses, all strains examined were shown to use SLAMs of their respective
      host species, and laboratory strains passaged on SLAM-negative cells were found
      to use, besides SLAM, alternative receptors, such as human CD46 for the Edmonston
      strain of MV. The use of SLAM as a receptor may be a property common to most, if
      not all, of the members of morbilliviruses. Human SLAM is a membrane glycoprotein
      selectively expressed on the cells of the immune system (immature thymocytes,
      activated lymphocytes, activated monocytes, and mature dendritic cells) and seems
      to mediate lymphocyte activation and to control interferon-gamma production. The
      destruction and/or impairment of infected SLAM-positive cells may be a mechanism
      for the immunosuppression induced by morbilliviruses, but other mechanisms may be
      also involved.

PMID- 12008922
TI  - Antigenic relatedness between Burkholderia pseudomallei and Burkholderia mallei.
AB  - Burkholderia pseudomallei and Burkholderia mallei are causative agents of
      distinct diseases, namely, melioidosis and glanders, respectively. The two
      species are very closely related, based on DNA-DNA homology, base sequence of the
      16S rRNA, and phenotypic characteristics. Based on the use of polyclonal
      antisera, B. pseudomallei and B. mallei are also found to be antigenically
      closely related to one another. We previously reported the production of
      monoclonal antibodies (MAbs) against B. pseudomallei antigens; one group was
      specific for the 200-kDa exopolysaccharide present on the surface of all B.
      pseudomallei isolates, and the other was specific for the lipopolysaccharide
      (LPS) structure present on more than 95% of the B. pseudomallei tested. In the
      present study, we showed that the MAbs against 200-kDa antigen of B. pseudomallei
      cross-reacted with a component present also in some B. mallei isolates (3/6), but
      the positive immunoblot reaction was noted below the 200-kDa position. On the
      other hand, none of the six B. mallei isolates reacted with the MAb specific for
      B. pseudomallei LPS. It was of interest to observe that only the 3
      exopolysaccharide-positive B. mallei isolates reacted with a commercial MAb
      against B. mallei LPS. The data presented suggest that B. mallei can be
      classified antigenically into two types based on their reactivities with
      different MAbs, i.e., the presence or absence of exopolysaccharide and the types
      of lipopolysaccharide. The heterogeneity of the LPS from these two closely
      related organisms is most likely related to the differences in its O
      polysaccharide side chain.

PMID- 12008923
TI  - Signaling pathways induced by lipoproteins derived from Mycoplasma salivarium and
      a synthetic lipopeptide (FSL-1) in normal human gingival fibroblasts.
AB  - Lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL
      1) activate human gingival fibroblasts to induce IL-6 production and ICAM-1
      expression. Human gingival fibroblasts were treated with lipoproteins or FSL-1
      and then examined for the activation of mitogen-activated protein kinases
      (MAPKs), ERK1/2, p38, and SAPK/JNK, and transcription factors, AP-1 and NF
      kappaB. Western blotting indicated that p38 and SAPK/JNK were activated in
      response to the stimulators, but the activation of ERK1/2 could not be
      discriminated because ERK1/2 was activated in the absence of stimulators. The p38
      inhibitor SB 203580 also suppressed their IL-6 production-inducing activities,
      whereas the ERK1/2-activating MAPK kinase (MEK1) inhibitor PD 98059 did not
      suppress their activities. Moreover, they were capable of inducing the activation
      of AP-1 and NF-KB. NF-kappaB activation was also confirmed by the phosphorylation
      of IkappaB-alpha. On the basis of these results, it was concluded that
      lipoproteins of M. salivarium and FSL-1 are capable of activating the MAPKs p38
      and SAPK/JNK and the transcriptional factors AP-1 and NF-kappaB in human gingival
      fibroblasts.

PMID- 12008924
TI  - The 44-kb linear plasmid molecule in the relapsing fever agent Borrelia duttonii
      strain Ly serve as a preservation of vmp genes.
AB  - Borrelia duttonii strain Ly, a causative agent of relapsing fever, contains a
      linear one megabase chromosome and 12 linear plasmid molecules. Here we report
      that the sequence of the 44-kb linear plasmid of strain Ly is found to contain
      variable major protein (vmp) genes for antigenic variation of relapsing fever
      borreliae. The determined sequence is of 44,010 bp except for both ends of the
      molecule. Of 39 open reading frames (ORFs) found in the sequence, 21 ORFs (named
      vmpA to U) showed moderate similarities with vmp genes for Borrelia hermsii.
      However, most of the vmp homologues are apparently nonfunctional because of their
      frameshifts within the sequence and/or absence of promoter and ribosome-binding
      signals upstream of their genes. RT-PCR experiments using the specific primer for
      each vmp gene revealed that vmpE, one of the vmp genes, was expressed at the
      location of the 44-kb plasmid molecule. The result suggests that the plasmid
      molecule may play a role in the preservation of the serotype switching of vmp
      genes in a mammalian host.

PMID- 12008925
TI  - Fine mapping of the subunit binding sites of influenza virus RNA polymerase.
AB  - Influenza virus RNA polymerase consists of three subunits, PB1, PB2 and PA, and
      catalyzes both transcription and replication of the RNA genome. PB1 is a
      catalytic subunit of RNA polymerization and a core of the subunit assembly. The
      subunit binding sites were mapped at about several hundred amino-acid size. Fine
      mapping of the subunit binding sites was determined. The PB1-PA binding regions
      were mapped within in the N-terminal 25 amino acids of PB1 and 668-692 of PA. PB1
      and PB2 interacted within wider regions, 600-757 of PB1 and 51-259 of PB2. In
      these amino-acid spans, 206-259 of PB2 may be the most important region of PB1
      binding and 718-732 of PB1 may be the most important region of PB2 binding
      because the binding activity was lost when the regions were lost in the subunits.
      The additional regions contributed to strong binding of these subunits.

PMID- 12008926
TI  - Detection of herpesvirus DNA in the serum of immunocompetent children.
AB  - The DNA of herpesviruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV),
      human herpesvirus-6 (HHV6), and human herpesvirus-7 (HHV7) has been detected in
      the serum of patients with primary infection or with immunosuppression. However,
      it is unknown how frequently herpesvirus DNA can be detected in the serum of
      immunocompetent children, or whether the detection of herpesvirus DNA indicates
      an active infection or virus-related diseases. Using a real-time polymerase chain
      reaction assay, attempts were made to detect herpesvirus DNA in the serum of 176
      ambulatory children who visited a hospital for various reasons. EBV was detected
      in 4 (2.2%), HHV6 in 4 (2.2%), and HHV7 in 2 (1.1%) of 176 children, but CMV was
      not detected. Of the 10 positive patients, only 4 were considered, by virtue of
      clinical and serological characteristics, to have primary infections. The other 4
      positive patients had other infections, such as mycoplasma and salmonella.
      Although herpesvirus DNA could be detected in the serum of immunocompetent
      children, there was not always a relationship between clinical manifestations and
      the detection of virus DNA. When herpesvirus DNA is detected in the serum, a
      careful interpretation is necessary to diagnose a primary infection or a virus
      associated disease.

PMID- 12008927
TI  - Anti-CD11 b monoclonal antibody suppresses brain dissemination of Cryptococcus
      neoformans in mice.
AB  - To elucidate the role of the beta2 integrin family of adhesion molecules in the
      disseminated infection of Cryptococcus neoformans from the lung to the central
      nervous system, we examined the effects of monoclonal antibodies (mAbs) against
      CD11a, CD11b, CD11c and CD18 on the number of live microorganisms in both the
      lung and brain of mice three weeks after intratracheal infection. Administration
      of anti-CD11b mAb partially, but reproducibly, reduced the fungal loads in the
      brain in three independent experiments, while the lung loads were not affected.
      In addition, the same treatment significantly decreased the number of live
      microorganisms in the blood. In sharp contrast, the brain loads one week after
      intravenous injection with C. neoformans were not affected by treatment with anti
      CD11b mAb. Finally, administration of mAb against other adhesion molecules
      (CD11a, CD11c or CD18) failed to affect the fungal loads in the brain as well as
      in the lung three weeks after intratracheal instillation, except for anti-CD18
      mAb which rather increased the brain loads. Our results suggested that CD11b
      might be involved at least in part in the process of fungal dissemination from
      lung to brain, although the significance of other beta2 integrin family adhesion
      molecules remains to be substantiated.

PMID- 12008928
TI  - Lactoferrin stimulates A Staphylococcus aureus killing activity of bovine
      phagocytes in the mammary gland.
AB  - Lactoferrin (Lf) may play a key role in the clearance of microorganisms from a
      host. To study in vitro the bactericidal mechanisms of Lf during nonlactating
      periods, we investigated whether the effects of Lf were influenced by bovine
      mammary gland secretory cells (MGSC) and fresh normal bovine serum (NBS) as a
      source of complement. Phagocytic killing tests demonstrated that a phagocytic
      mixture of unopsonized Staphylococcus aureus (S. aureus) and MGSC in the presence
      of Lf reduced bacterial growth, compared with that of unopsonized S. aureus and
      MGSC without Lf. The opsonization with Lf and fresh NBS together resulted in more
      than a 95% reduction in CFU. The activation of complement induced by Lf also
      resulted in increased deposition of C3 on S. aureus, and the phagocytic activity
      of MGSC was augmented by opsonization with Lf and fresh NBS. Inhibition of C3
      deposition by Lf was not induced in the presence of Mg-EGTA, but was induced by
      the addition of bovine Lf antiserum. These results strongly suggest that Lf
      induces the activation of complement in fresh NBS mainly through an alternative
      pathway. The results demonstrated a Lf-dependent, antibody-independent and
      complement-mediated phagocytic killing of S. aureus, and implied that Lf was
      synergistically capable of activating both the alternative pathway of the bovine
      complement cascade and phagocytosis by phagocytes.

PMID- 12008929
TI  - IL-10 producing CD14low monocytes inhibit lymphocyte-dependent activation of
      intestinal epithelial cells by commensal bacteria.
AB  - Intestinal epithelial cell (IEC) activation by non-pathogenic, commensal bacteria
      was demonstrated to require the presence of immunocompetent cells. In this study,
      HT-29 and CaCO-2 transwell cultures, reconstituted with CD4+ and CD8+ T cells,
      CD19+ B cells and CD14high monocytes, were challenged with non-pathogenic Gram
      negative Escherichia coli and Gram positive lactobacilli. Cytokine expression was
      analysed by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme
      linked immunosorbent assays (ELISA). Expression of tumour necrosis factor alpha
      (TNF-alpha) and interleukin (IL)-8 mRNA in E. coli or L. sakei challenged IEC was
      promoted by lymphocyte populations predominantly CD4+ T cells, while monocytes
      failed to mediate an inflammatory cytokine response. The monocyte phenotype and
      function were further characterised by flow cytometry and mixed lymphocyte
      reaction (MLR). During the co-culture with IEC and bacterial stimulated IEC,
      CD14high peripheral blood monocytes acquired a CD14low CD16low phenotype with
      reduced expression co-stimulatory (CD80, CD86, CD58) cell surface molecules.
      Immunosuppressive functions of IEC conditioned CD14low monocytes were
      demonstrated by the predominant secretion of IL-10 and IL-IRa and their reduced
      potential to trigger an allogeneic lymphocyte response. In conclusion, IEC
      contribute to the development of CD14low CD16low monocytes with immunosuppressive
      function and antagonised a lymphocyte-mediated activation of the intestinal
      epithelium in response to intestinal and food derived bacteria. These results
      strengthen the hypothesis that the gut epithelium constitutes an important
      functional element in the regulation of mucosal immune homeostasis towards
      commensal bacteria.

PMID- 12008930
TI  - Minimal contribution of Valpha14 natural killer T cells to Th1 response and host
      resistance against mycobacterial infection in mice.
AB  - We elucidated the contribution of Valpha14 NKT cells to Th1 response and host
      resistance against mycobacterial infection. In Valpha14 NKT cell-deficient mice,
      host defense and DTH response to Mycobacterium bovis BCG were not different from
      wild-type mice after pulmonary infection. There was no significant difference in
      the lung concentrations of IFN-gamma between the two strains of mice. In
      addition, host defense to systemic infection with M. tuberculosis was similar to
      that of M. bovis. Our results indicate that Valpha14 NKT cells play only a
      marginal role, if any, in the Th1 response and host resistance to mycobacterial
      infection.

PMID- 12008931
TI  - A novel genetic algorithm for designing mimetic peptides that interfere with the
      function of a target molecule.
AB  - We designed a new computer program (MIMETIC), which generates a series of
      peptides for interaction with a target peptide sequence. The genetic algorithm
      employed ranks the sequences obtained from one generation to the next by
      "goodness of fit" to the target. MIMETIC designed recognition peptides to various
      regions of HIV-1 reverse transcriptase. Among ten peptide candidates synthesized,
      three inhibited reverse transcription in vitro. TLMA2993 and PSTW1594 both
      targeted the connection domain of reverse transcriptase and ESLA2340 targeted the
      thumb domain.

PMID- 12008932
TI  - Heat stability of carboxypeptidase R of experimental animals.
AB  - Carboxypeptidase N (CPN) and carboxypeptidase R (CPR) are present in fresh serum,
      and cleave C-terminal arginine or lysine residues from bioactive peptides such as
      anaphylatoxins and kinins resulting in regulation of peptide activity. Although
      CPN is present in the active form in plasma, CPR is generated from proCPR by
      trypsin-like enzymes such as thrombin. CPR regulates not only inflammatory
      peptides but also restricts fibrinolysis. To elucidate the complex role of CPN
      and CPR in vivo, studies in animal models will be essential. CPR of guinea pig,
      rat and rabbit decayed at 37 C rapidly as in the case of human CPR. However, at
      25 C, CPR of those species decayed to some extent, although human serum CPR did
      not decay within 60 min. In the presence of thrombin inhibitor, CPR in the sera
      of animals tested decayed more rapidly than CPR in serum without thrombin
      inhibitor suggesting that additional generation of CPR may have been prevented
      during decay evaluation. However, human serum CPR decayed more rapidly in the
      absence of thrombin inhibitor indicating that thrombin may accelerate the decay
      in human serum.

PMID- 12008933
TI  - Elastase from activated human neutrophils activates procarboxypeptidase R.
AB  - Carboxypeptidase R (EC 3.4.17.20; CPR) is an unstable basic carboxypeptidase
      found in fresh serum in addition to carboxypeptidase N (CPN) which is a stable
      enzyme. CPR in fresh serum is generated from its zymogen (proCPR) during
      coagulation by trypsin-like enzymes such as thrombin and thrombin/thrombomodulin
      complexes. Since removal of the C-terminal arginine abrogates the anaphylatoxin
      activity of C3a and C5a, CPR and CPN are regarded as anaphylatoxin inactivators.
      We report here that the culture supernatant of activated human neutrophils
      converts proCPR to CPR. Addition of an elastase specific inhibitor, N
      methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone (MSAAPVCK) to the supernatant
      of stimulated neutrophils completely inhibited activation of proCPR. On the other
      hand, a thrombin specific inhibitor, p-Nitrophenyl-p'-amidinophenyl
      methanesulfonate hydrochloride (pNP-pAPMS) inhibited only 16% of proCPR
      activation by the neutrophil supernatant. Furthermore, purified elastase
      converted proCPR to CPR. Therefore, elastase can activate proCPR directly, or
      indirectly through activation of some proteases, which have been contaminating in
      reagents. Release of CPR generating enzymes from neutrophils should play an
      important role in regulation of excess inflammation.

PMID- 12008934
TI  - Maximized hemostasis.

PMID- 12008935
TI  - Local proCPU (TAFI) activation during thrombolytic treatment in a dog model of
      coronary artery thrombosis can be inhibited with a direct, small molecule
      thrombin inhibitor (melagatran).
AB  - To test the hypothesis that the direct thrombin inhibitor, melagatran is able to
      inhibit local pro-carboxypeptidase U (proCPU) activation that occurs during
      thrombolytic treatment, t-PA alone, or in combination with melagatran, was given
      to dogs with a coronary artery thrombosis. Blood samples from the great cardiac
      vein and aorta were collected at baseline, during thrombus formation, throughout
      the t-PA+/-melagatran infusion and during the patency period, for analysis of CPU
      activity using a novel assay. A higher CPU activity in venous compared to
      arterial blood (V-A difference) indicates CPU activation in coronary vessels.
      Efficacy was assessed by determination of time to lysis, duration of patency and
      blood flow during patency. Dogs (n = 26) were randomized to receive either 1) t
      PA, 1 mg/kg as an intravenous 20-min infusion; 2) t-PA as in group 1, +melagatran
      bolus, 0.3 mg/kg, followed by a 3-h infusion (0.15 mg/kg per h); 3) sham-operated
      but no coronary thrombus, and administered t-PA as for Group 1. All groups had
      similar baseline characteristics. Significant increases in CPU activity were
      observed in Groups 1 and 2 during thrombus formation, with V-A differences of 5.5
      and 4.5 U/L, respectively. No significant V-A difference was observed in the sham
      operated group. CPU activity increased in Group 1 during the t-PA infusion (V-A
      difference 15.9 U/L), whereas the V-A difference in Group 2 decreased to 2.6 U/L
      following melagatran treatment. These results demonstrate that melagatran
      attenuates generation of CPU in the coronary circulation. The mechanism is
      probably indirect, via inhibition of thrombin-mediated activation of proCPU.

PMID- 12008936
TI  - Mouse models in coagulation.

PMID- 12008937
TI  - Venous thrombosis in patients with solid tumors: determination of frequency and
      characteristics.
AB  - Deep venous thrombosis (DVT) and pulmonary embolism (PE) are well recognized
      complications of cancer. However, our current knowledge of this association is
      derived from studies conducted more than a decade ago. In light of the changes in
      medical practice and the improvement in cancer care in recent years, a re
      evaluation of the relationship between malignancy and venous thrombosis is in
      order. Of a total of 1041 patients with solid tumors admitted to 3 major medical
      centers, there were 81 (7.8%) diagnosed with DVT/PE. Patients were more likely to
      develop DVT/PE during chemotherapy (p = .0001). Advanced malignancies (p = .001),
      renal carcinoma (p = .005), pancreatic (p = .001), gastric (p = .014) and brain
      tumors (p = .001) were independent variables strongly associated with the
      occurrence of venous thrombosis. The occurrence of thrombotic events in the
      population tested in this study did not adversely affect survival (p = .082). The
      study identifies subset of patients with cancer at high risk for venous
      thrombosis. Early prophylaxis with anticoagulants in these patients may be
      warranted. Most importantly, further clinical trials are desperately awaited to
      detect possible new trends in the frequency and types of thrombotic events and to
      better define prevention strategies in cancer patients at risk for thrombosis.
      The association between venous thromboembolic disease (VTD) and malignant
      neoplastic disorders is well known and has been the subject of several reports
      for more than a century. There is a general agreement among investigators that
      thrombotic complications in patients with cancer occur at a rather high
      frequency, and that other circumstantial factors such as surgery or chemotherapy
      potentiates this risk. However, several important considerations pertaining to
      cancer and thrombosis continue to be shrouded in controversy. For example, there
      are inexplicable differences in the proportion of patients with cancer diagnosed
      with deep venous thrombosis (DVT) or pulmonary embolism (PE) reported in the
      literature. In the absence of large well-controlled studies, one may only
      postulate on the reasons that contributed to these differences. The inclusion of
      different types of VTD such as superficial, venous, arterial or vascular access
      device-induced thrombosis may have led to overestimation of the incidence of
      these events in patients with underlying malignancy. Another possible explanation
      for this discrepancy relates to the use of a variety of diagnostic and
      methodological criteria ranging from observation and clinical suspicion to more
      invasive procedures resulting in considerable differences in the rate of reported
      clotting events. Along the same line of discussion, one may argue whether VTD is
      a random event or constitutes a complication that occurs more commonly in
      patients with distinct characteristics and certain tumor types. To further
      investigate the association between malignancy and thrombosis, we evaluated 1041
      patients with solid tumors for the risk of DVT/PE. The main objectives of the
      study were to determine the frequency of DVT/PE based on validated diagnostic
      criteria and to identify patients with cancer at high risk for developing these
      thrombotic episodes. Also, we evaluated the impact of VTD on the survival of
      these patients.

PMID- 12008938
TI  - Factor V Leiden (G1691A) and prothrombin gene G20210A mutations as potential risk
      factors for venous thromboembolism after total hip or total knee replacement
      surgery.
AB  - Patients (n = 1600) from 12 European countries, scheduled for elective
      orthopaedic hip or knee surgery, were screened for Factor V Leiden and
      prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations,
      respectively. All patients underwent prophylactic treatment with one of four
      doses of melagatran and ximelagatran or dalteparin, starting pre-operatively.
      Bilateral ascending venography was performed on study day 8-11. The patients were
      subsequently treated according to local routines and followed for 4-6 weeks
      postoperatively. The composite endpoint of screened deep vein thrombosis (DVT)
      and symptomatic pulmonary embolism (PE) during prophylaxis did not differ
      significantly between patients with or without these mutations. Symptomatic
      venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was
      significantly over-represented among patients with the prothrombin gene G20210A
      mutation (p = 0.0002). A tendency towards increased risk of VTE was found with
      the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over
      represented in both the Factor V Leiden and prothrombin gene G20210A mutated
      patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the
      patients with these genetic risk factors will not suffer a VTE event, a general
      pre-operative genotyping is, in our opinion, of questionable value.

PMID- 12008939
TI  - Out of hospital antithrombotic prophylaxis after total hip replacement: low
      molecular-weight heparin, warfarin, aspirin or nothing? A cost-effectiveness
      analysis.
AB  - Several studies have suggested that after hip replacement the risk of deep vein
      thrombosis and subsequent pulmonary embolism (PE) may persist for some weeks.
      Antithrombotic prophylaxis, however, is generally stopped at hospital discharge.
      Using a Markov-based decision analysis, we measured the clinical and economical
      consequences of extending prophylaxis after hospital discharge up to 4 weeks and
      6 weeks, using either low-molecular-weight heparin (LMWH), warfarin, or aspirin.
      In the reference strategy, antithrombotic prophylaxis was stopped at hospital
      discharge. Outcome measures included the number of PE prevented, major
      haemorrhages induced, overall costs in Euro (EUR) and specific costs generated by
      each PE prevented for all strategies. Extending prophylaxis up to 4 weeks after
      discharge was safe and cost saving for all prophylactic regimens, although LMWH
      was the most effective strategy. Our results were most sensitive to the rate of
      haemorrhages, the efficacy of treatment and its costs. Specifically, the number
      of PEs prevented exceeded that of haemorrhages induced if the efficacy of
      antithrombotic prophylaxis was > or = 40% (assuming a low rate of haemorrhages of
      0.1% per week), and > or = 70% (assuming a high rate of haemorrhages of 0.25% per
      week). LMWH and warfarin remained cost saving unless their costs were more than
      doubled compared to that of baseline value. Although less effective than LMWH and
      warfarin, prophylaxis with aspirin was cost saving in all scenarios tested.
      Extending prophylaxis up to 6 weeks was also effective (the number of PEs
      prevented overwhelmed that of major haemorrhages induced), but only for the
      scenario of a low bleeding risk (0.1%/week). In this strategy, aspirin remained
      cost saving, while the costs for each PE prevented became high (EUR 10,000 to EUR
      20,000) if the costs of LMWH and warfarin increased. After hip replacement,
      extending antithrombotic prophylaxis up to 4 weeks after hospital discharge is
      effective and cost saving. Although LMWH is the most effective strategy,
      warfarin, and to a lesser extent aspirin may be alternate options if ressources
      are a major concern. Extending prophylaxis up to 6 weeks is more risky in
      patients at high bleeding risk, and generates additional costs.

PMID- 12008940
TI  - Comparison of venography and ultrasound for the diagnosis of asymptomatic deep
      vein thrombosis in the upper body in children: results of the PARKAA study.
      Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase.
AB  - Deep vein thrombosis (DVT) in children occurs primarily in the upper body venous
      system. This prospective diagnostic study compared bilateral venography and
      ultrasound for detection of DVT in the upper venous system in 66 children with
      acute lymphoblastic leukemia. Results were interpreted by central blinded
      adjudication. Deep venous thrombosis occurred in 29% (19/66) patients. While
      15/19 DVT were detected by venography (sensitivity 79%), only 7/19 were detected
      by ultrasound (sensitivity 37%). The 12 DVT detected by venography but not by
      ultrasound were located in the subclavian vein or more central veins. Three of 4
      DVT detected by ultrasound but not by venography were in the jugular vein. We
      conclude that ultrasound is insensitive for DVT in the central upper venous
      system but may be more sensitive than venography in the jugular veins. A
      combination of both venography and ultrasound is required for screening for DVT
      in the upper venous system.

PMID- 12008941
TI  - Distinguishing features of anti-beta2 glycoprotein I antibodies between patients
      with leprosy and the antiphospholipid syndrome.
AB  - Anticardiolipin (ACA), anti-beta2 glycoprotein I (beta2GPI), and antiprothrombin
      antibodies of IgG and IgM classes were quantitated by enzyme-linked immunosorbent
      assays in 176 untreated leprosy patients across the histopathological spectrum.
      Positivity rates ranged from 21% (IgG ACA) to 30% (IgM anti-prothrombin) versus
      4% in healthy controls (p <10(-2) to 10(-3)). Levels of IgM anti-beta2GPI and IgG
      ACA were significantly higher in lepromatous leprosy and multibacillary patient
      subgroups. IgG3 was the most common subclass reactive to both beta2GPI and
      prothrombin in selected high-titer leprosy sera, unlike antibodies from patients
      with the antiphospholipid syndrome (APS) largely restricted to IgG2. In leprosy
      patients, but not in the APS control group, there was no statistical correlation
      between ACA and anti-beta2GPI antibody levels. Likewise, a large fraction of anti
      beta2GPI positive sera (36/45 and 28/44 for IgG and IgM, respectively) were
      unreactive in the standard ACA assay. Most assayed anti-beta2GPI antibodies from
      leprosy patients showed (i) ability to recognize both human and bovine beta2GPI
      immobilized on non-irradiated polystyrene plates, (ii) concentration-dependent
      inhibition of binding by cardiolipin, and (iii) relatively high avidity binding
      to fluid-phase beta2GPI, thereby differing from those found in APS. Finally, the
      location of the major epitopic region on the beta2GPI molecule targeted by
      autoantibodies was different in leprosy and APS, as assessed by direct binding to
      domain I- and V-deleted mutants and competition with the mouse monoclonal
      antibody 8C3, directed at domain I. Thus, leprosy-related antiphospholipid
      antibodies comprise persistent IgG and IgM anti-beta2GPI that differ from APS
      related ones with respect to IgG subclass, avidity and epitope specificity,
      possibly reflecting distinct pathophysiological significance.

PMID- 12008942
TI  - Decreased concentrations of heparinoids are required to inhibit thrombin
      generation in plasma from newborns and children compared to plasma from adults
      due to reduced thrombin potential.
AB  - Thrombin generation is decreased and delayed in plasma from newborns and children
      compared to adults. We hypothesized that lower doses of heparinoid anticoagulants
      are required to give similar thrombin generation in newborn (umbilical cord) and
      child plasmas compared to that of adults. Thrombin generation was performed in
      either the absence or presence of unfractionated heparin (UFH), low molecular
      weight heparin (LMWH) or a covalent antithrombin-heparin complex (ATH). After
      contact activation and recalcification of each plasma, thrombin activity was
      measured by periodic sub-sampling into chromogenic substrate. UFH inhibited
      thrombin generation to a greater extent compared to LMWH in all plasmas. Cord
      plasma was more sensitive to inhibition and displayed a greater difference in the
      effectiveness of UFH compared to LMWH than other plasmas. Lower concentrations of
      UFH and LMWH were required to inhibit thrombin generation in cord and child
      plasmas compared to adult plasma. In comparison, ATH strongly inhibited thrombin
      generation in all 3 plasmas. Similar peak thrombin concentrations were observed
      at lower ATH concentrations (0.1 U/mL) compared to either UFH (0.25 U/mL) or LMWH
      (0.25 U/mL). As with UFH and LMWH, cord plasma was more sensitive to inhibition
      by ATH than the other plasmas and lower ATH concentrations inhibited thrombin
      generation in cord and child plasmas compared to adult plasma. Decreased thrombin
      generation with heparinoids in cord and child plasmas compared to adult plasma
      coincided with decreased rates of prothrombin consumption and increased
      proportion of thrombin-alpha2-macroglobulin inhibitor complexes. In summary,
      lower doses of UFH, LMWH or ATH result in similar peak thrombin generation in
      newborn and child plasmas compared to adult plasma. Cord plasma was the most
      sensitive to inhibition, with ATH being more effective than UFH or LMWH.

PMID- 12008943
TI  - No association of plasma prothrombin concentration or the G20210A mutation with
      incident cardiovascular disease: results from the Cardiovascular Health Study.
AB  - Prothrombin is a key factor in blood clotting, a process intimately involved in
      thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case
      control study within the Cardiovascular Health Study. Cases included angina,
      myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n
      approximately 250 each). Population-based controls free of clinical
      cardiovascular disease (CVD) (n approximately 500) and a subset free of clinical
      and subclinical CVD (n approximately 250) were used for comparison. The 20210 A
      allele, frequency 2.9%, was associated with higher mean prothrombin levels: 166.3
      vs. 139.5 microg/ml (P <0.001). Significant correlates of prothrombin included
      gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory
      markers, but not race, smoking, hypertension, diabetes, measures of subclinical
      CVD, or markers of procoagulant activity. Compared to controls, neither genotype
      nor prothrombin level was associated with any CVD case group. We conclude that,
      in the elderly, neither prothrombin level nor 20210 genotype were associated with
      either CVD risk factors or events. This is consistent with the lack of
      association of prothrombin levels with measures of underlying CVD or procoagulant
      markers.

PMID- 12008944
TI  - A prospective evaluation of the heat shock protein 70 gene polymorphisms and the
      risk of stroke.
AB  - Genetic polymorphisms of heat shock protein 70-kD (HSP70) gene family have
      recently been hypothesized to be risk factors for cerebral ischemia. However, no
      prospective epidemiological data evaluating this gene family are available. The
      present investigation was conducted to examine the possible associations between
      the HSP70-1 nucleotide 190. HSP70-2 nucleotide 1267, and HSP70-hom nucleotide
      2437 polymorphisms and the incidence of stroke in a large cohort of initially
      healthy men. 14916 apparently healthy men were followed over a 12-year period for
      incident stroke. Employing a nested case-control study design, 338 study
      participants who developed stroke (cases) and 338 age- and smoking-matched study
      participants who remained healthy during follow-up (controls) were evaluated. All
      observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and
      genotype distributions of the polymorphisms tested were similar among cases and
      controls, such that the relative risk of future stroke was 0.89 for HSP70-1
      nucleotide 190 (95%CI = 0.70-1.12; p = 0.31), 1.13 for HSP70-2 nucleotide 1267
      (95%CI = 0.90-1.42: p = 0.29); and 0.89 for HSP70-hom nucleotide 2437 (95%CI =
      0.65-1.21; p = 0.45), assuming an additive model. No evidence of association was
      observed assuming dominant or recessive mode of inheritance. In this large,
      prospective study, genetic polymorphisms in the HSP70 genes were not associated
      with risks of future stroke. Screening for these polymorphisms is unlikely to be
      a useful tool for risk assessment.

PMID- 12008945
TI  - Antibodies to heterologous proteins in hemophilia A patients receiving
      recombinant factor VIII (Recombinate).
AB  - As a consequence of the manufacturing process, trace quantities of Chinese
      hamster ovary cell protein, bovine serum albumin and murine immunoglobulin G are
      present in Recombinate recombinant human factor VIII (rhFVIII). The development
      of antibodies (Abs) to these heterologous proteins was evaluated during long-term
      rhFVIII therapy of hemophilia A in 68 previously treated and 73 previously
      untreated patients. Ab prevalence was also assessed in 157 non-hemophilic
      subjects. Abs against heterologous proteins could be detected in varying
      percentages of patients and non-hemophilic subjects. Abs arose in patients
      sporadically, and levels were typically low. There were no adverse events
      associated with development or presence of anti-heterologous protein Abs. These
      data indicate that sustained immune responses to trace levels of heterologous
      proteins are very infrequent during long-term rhFVIII therapy.

PMID- 12008946
TI  - Identification of a new type 2M von Willebrand disease mutation also at position
      1324 of von Willebrand factor.
AB  - Type 2M von Willebrand disease (VWD) refers to variants with decreased platelet
      dependent function that is not associated with the loss of high molecular weight
      (HMW) von Willebrand factor (VWF) multimers. This category includes the so-called
      "phenotype B" responsible for inexistent ristocetin-induced but normal botrocetin
      induced binding of VWF to platelet glycoprotein lb. The missense mutation G1324S
      was identified in the first patient reported to display "phenotype B". We report
      here on the identification in four members of a French family of a missense
      mutation also affecting this glycine residue but changing it into an alanine
      residue. These individuals are heterozygous for this mutation and two of them
      display an additional quantitative VWF deficiency resulting from a stop codon at
      position 2470. After transient transfection in Cos-7 cells, the mutated
      recombinant protein harbouring the G1324A substitution was shown to exhibit
      normal multimers and inexistent ristocetin-induced but normal botrocetin-induced
      binding to GPIb, confirming the classification of this new mutation as a type 2M
      VWD mutation.

PMID- 12008947
TI  - Purification and characterization of a novel metalloproteinase, acurhagin, from
      Agkistrodon acutus venom.
AB  - Acurhagin, a high-molecular mass hemorrhagic metalloproteinase, was purified from
      the crude venom of Agkistrodon acutus using anion-exchange and hydrophobic
      interaction chromatography. Acurhagin is a monomer with a molecular mass of 51.4
      kDa under non-reducing conditions on SDS-PAGE and 48,133 Da by mass spectrometry.
      Partial amino acid sequence of its metalloproteinase domain is homologous to
      other high-molecular mass metalloproteinases from snake venoms. It preferentially
      cleaved Aalpa chain of fibrinogen, followed by Bbeta chain, while gamma chains
      was minimally affected. Monitored by RP-HPLC, it extensively degraded fibrinogen
      into various peptide fragments. In aqueous solution, acurhagin autoproteolyzed to
      a 30 kDa fragment at 37 degrees C. The N-terminal sequence of the 30 kDa fragment
      of acurhagin showed a high homology to those proteins consisting of disintegrin
      like and cysteine-rich domains. Caseinolytic assay showed that the proteinase
      activity of acurhagin was slightly enhanced by Ca2+ and Mg2+, but completely
      inhibited by Zn2+. When treated with metal chelators, acurhagin was completely
      inactivated. Furthermore, acurhagin exerts an inhibitory effect on ADP-induced
      platelet aggregation of platelet-rich plasma in an incubation-time dependent
      manner. It also impairs collagen- and ristocetin-induced platelet aggregation by
      cleaving collagen and vWF, respectively.

PMID- 12008948
TI  - Fibrinogen assembly and crosslinking on a fibrin fragment E template.
AB  - There is an ongoing controversy concerning whether crosslinked gamma chains in
      fibrin are oriented "transversely" between fibril strands or "end-to-end" along
      fibril strands. From the latter viewpoint, Veklich et al. [Proc Natl Acad Sci
      (USA) 95: 1438, 1998] observed that fibrinogen fibrils that had been assembled on
      a fibrin fragment E template, cross-linked with factor XIIIa, and then
      dissociated in acetic acid solution, were aligned end-to-end. This led to the
      conclusion that crosslinked gamma chains in fibrin under physiological conditions
      were also aligned end-to-end. To assess its validity we studied the assembly and
      organization of fibrinogen molecules on a des AB-fibrin fragment E (E-des AB) or
      a des A-fibrin fragment E (E-des A) template. We evaluated the roles of E
      polymerization sites E(A) and E(B), and D association sites gammaXL, Da, Db,
      betaC and alphaC in this process. E(A):Da interactions caused fibrinogen: E "DED"
      complexes to form, and markedly enhanced the gamma chain crosslinking rates of
      fibrinogen or des alphaC-fibrinogen. Fibrinogen crosslinking without added fibrin
      E was slower, and that of des alphaC-fibrinogen was still slower. These events
      showed that although alphaC domains promote fibrinogen fibril assembly and
      crosslinking, they contribute little to increasing the E(A):Da-dependent
      crosslinking rate. Electron microscopic (STEM) images of E-des AB and fibrinogen
      plus factor XIIIa showed single-, double-, and multistranded fibrils with
      interstrand DED complexes aligned side-to-side. This alignment was due to
      betaC:betaC contacts resulting from D subdomain rearrangements initiated by the
      E(B):Db interactions, and also occurred in mixtures of des alphaC-fibrinogen with
      E-des AB. In contrast, a mixture of fibrinogen and E-des A plus XIIIa revealed
      double-stranded fibrils with interstrand DED complexes in a half-staggered
      arrangement, an alignment that we attribute to crosslinking of gammaXL sites
      bridging between fibrils strands. These and other features of E-des A-based
      fibrinogen fibrils, including interstrand gamma chain bridges and early and
      extensive lateral fibril strand associations concomitant with accelerated gamma
      chain crosslinking, indicate that crosslinking of fibrin fibril strands takes
      place preferentially on transversely positioned gamma chains.

PMID- 12008949
TI  - Aberrant splicing and premature termination of transcription of the FVIII gene as
      a cause of severe canine hemophilia A: similarities with the intron 22 inversion
      mutation in human hemophilia.
AB  - We have identified the causative mutation in the hemophilia A dog colony at
      Queen's University, Canada and have observed a striking similarity with the
      intron 22 inversion found in approximately 45% of severely affected hemophilia A
      patients. The canine hemophilia A phenotype arises from aberrant splicing and
      premature termination of transcription of the FVIII gene, resulting in a
      polyadenylated transcript lacking exons distal to 22 and terminating with a novel
      sequence element (NSE). In dogs and other species including humans, this NSE is
      present in low copy number. One copy of these sequences in the canine genome is
      within intron 22 and reveals differences in the hybridization banding patterns
      between normal and hemophilic DNA, suggestive of a large genomic rearrangement.
      The mutation mechanism may not be uncommon, as identical mutant transcripts were
      isolated from two hemophilia A littermates that are unrelated to the Queen's
      colony and from hemophiliac dogs in the colony at Chapel Hill.

PMID- 12008950
TI  - Elimination of a human T-cell region in staphylokinase by T-cell screening and
      computer modeling.
AB  - Staphylokinase is a potent highly fibrin-selective thrombolytic agent, but it
      induces a humoral immune response in most treated patients. Staphylokinase
      specific T-lymphocytes can be found in normal healthy individuals, from whom a
      large panel of staphylokinase-specific T-cells were cloned. The staphylokinase
      amino acid sequence 71-87 was widely recognized, as it induced proliferation of T
      cell clones isolated from 90% of the donors. Computer modeling of this area,
      threaded as 11-mer peptides within the peptide-binding groove of the major HLA-DR
      alleles, indicated two putative partially overlapping binding sequences. The
      region-(71-87)-specific T-cell clones recognized either one or the other minimal
      peptide, confirming that both sequences could be functional T-cell epitopes.
      Furthermore, to guide the mutagenesis to eliminate T-cell reactivity, the
      contribution of each residue to the HLA-DR-anchoring and T-cell receptor exposure
      was evaluated for both binding motifs. Computer calculations combined with
      functional assays resulted in the design of staphylokinase-variants, including 2
      to 4 amino acid substitutions in the region 71-87. These variants were no longer
      recognized by the region-(71-87)-specific T-cell clones, and importantly no new
      staphylokinase-variant-specific cellular immune response could be measured.

PMID- 12008951
TI  - Differential effects of fibroblast growth factors on expression of genes of the
      plasminogen activator and insulin-like growth factor systems by human breast
      fibroblasts.
AB  - In breast stroma urokinase plasminogen activator (uPA) is predominantly expressed
      by fibroblasts located in the near vicinity of tumor cells, and fibroblast
      derived insulin-like growth factor-1 (IGF-1) may be involved in inhibiting the
      expression of uPA in these fibroblasts. To investigate a possible role for
      fibroblast growth factors (FGFs), we evaluated the expression of components of
      the PA system and the IGF system in normal and tumor-tissue-derived human breast
      fibroblasts exposed to various FGFs in vitro. mRNA analysis revealed that FGF-1,
      FGF-2 and FGF-4 induced the mRNA expression levels of uPA, tPA, uPAR, PAI-1 and
      PAI-2, and reduced those of IGF-1, IGF-1R, IGF-2R and IGFBP-4, without
      significantly affecting the levels of IGFBP-3, IGFBP-5 and IGFBP-6 mRNA.
      Concerning the expression of IGF-2 mRNA, the effects mediated by FGF-1, FGF-2 and
      FGF-4 were divergent. In general, the effects elicited by FGF-1 on the various
      mRNA levels studied were rapid and short-term. Those mediated by FGF-2 overall
      lagged behind but were longer-lasting. For FGF-4 an in between pattern was
      observed. Blocking transcription and translation demonstrated that a) both the
      FGF-1 and FGF-2 induced effects were the result of altered gene transcription or
      mRNA stability, b) the short-term effects mediated by FGF-1 and FGF-2 required de
      novo protein synthesis, and c) the long-term effects elicited by FGF-2 did not
      depend on de novo protein synthesis during the first 24 h, but were triggered by
      proteins produced or made available thereafter. The data presented propose that
      of the FGFs studied (FGF-1, -2, -4, -5, and -7), FGF-2 is the most attractive
      target for therapeutical strategies aimed at diminishing the contribution of
      stromal fibroblasts in the PA-directed breast tumor proteolysis.

PMID- 12008952
TI  - Nonsense mutation in exon-19 of GPIIb associated with thrombasthenic phenotype.
      Failure of GPIIb(delta597-1008) to form stable complexes with GPIIIa.
AB  - We report the molecular genetic analysis of a patient with thrombasthenic
      phenotype. The lack of surface platelet GPIIb-IIIa complexes and the presence of
      GPIIIa suggested it was a case of type I Glanzmann's thrombasthenia due to a
      mutation in GPIIb. Single stranded conformational polymorphism analysis (SSCP) of
      exon-19 of GPIIb showed polymorphic DNA bands. The DNA sequence of exon-19
      revealed the presence of a homozygous C1882T transition that changes residue R597
      to STOP codon. Since no other mutations were found in either GPIIb or GPIIIa it
      is concluded that the C1882T substitution in GPIIb is responsible for the
      thrombasthenic phenotype of the patient. The lack of platelet GPIIb-mRNA in the
      proband indicates instability of the [C1882T]GPIIb-mRNA. Coexpression of normal
      GPIIIa and GPIIb(delta597-1008) in CHO cells failed to show surface expression of
      GPIIb(delta597-1008)-IIIa complexes. Immunoprecipitation analysis demonstrated
      that GPIIb(delta597-1008) may indeed complex GPIIIa; however, the association is
      either unstable or incapable of progressing along the secretory pathway.

PMID- 12008953
TI  - Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent
      platelet agonist acting via GPIb and GPVI.
AB  - Alboluxin, a potent platelet activator, was purified from Trimeresurus albolabris
      venom with a mass of 120 kDa non-reduced and, after reduction, subunits of 17 and
      24 kDa. Alboluxin induced a tyrosine phosphorylation profile in platelets that
      resembles those produced by collagen and convulxin, involving the time dependent
      tyrosine phosphorylation of Fc receptor gamma chain (Fc gamma), phospholipase
      Cgamma2 (PLCgamma2), LAT and p72SYK. Antibodies against both GPIb and GPVI
      inhibited platelet aggregation induced by alboluxin, whereas antibodies against
      alpha2beta1 had no effect. Inhibition of alphaIIb beta3 reduced the aggregation
      response to alboluxin, as well as tyrosine phosphorylation of platelet proteins,
      showing that activation of alphaIIb beta3 and binding of fibrinogen are involved
      in alboluxin-induced platelet aggregation and it is not simply agglutination. N
      terminal sequence data from the beta-subunit of alboluxin indicates that it
      belongs to the snake C-type lectin family. The C-type lectin subunits are larger
      than usual possibly due to post-translational modifications such as
      glycosylation. Alboluxin is a hexameric (alphabeta)3 snake C-type lectin which
      activates platelets via both GPIb and GPVI.

PMID- 12008954
TI  - Release from intracellular stores is responsible for calcium signaling with von
      Willebrand factor in human platelets.
AB  - Interaction of von Willebrand factor (VWF) with the platelet promotes hemostasis
      upon vascular injury. Such interaction raises intracellular free calcium
      concentration ([Ca2+]i) and induces platelet activation. The platelet [Ca2+]i
      increase is generally attributed to influx across the plasma membrane. The
      present study defined the contribution of intracellular calcium stores. Platelet
      [Ca2+]i was monitored with Fura-PE3. Ristocetin-mediated binding of VWF
      transiently elevated [Ca2+]i after a lag phase. Studies with 63 healthy donors
      consistently revealed a VWF-induced platelet [Ca2+]i signal in the absence of
      extracellular calcium; there was only modest enhancement with extracellular
      calcium. Blockade of plasma membrane calcium channels did not diminish the
      signal, whereas depletion or blockade of the intracellular calcium stores
      abolished it. These findings imply that release from intracellular stores is
      responsible for the VWF-induced platelet [Ca2+]i increase. Influx across the
      plasma membrane plays no more than a minor role, probably representing
      "capacitative entry" to refill the intracellular stores.

PMID- 12008955
TI  - A 28-kDa glycoprotein functions as a platelet ligand for P-selectin (CD62P).
AB  - P-selectin (CD62P) is expressed on activated platelets and on stimulated
      endothelial cells. It interacts with P-selectin glycoprotein ligand-1 (PSGL-1;
      CD162) for adhesion of activated platelets on leukocytes and for rolling of
      leukocytes on stimulated endothelial cells. Recently, resting and activated
      platelets have been shown to roll on endothelial P-selectin, indicating that
      platelets express (a) ligand(s) for P-selectin. Here we show that P-selectin
      specifically precipitated one 28-kDa glycoprotein from the whole cell lysates and
      the membrane lysates of human platelets in a Ca2+-dependent manner. Further, the
      purified 28-kDa molecule could inhibit the binding of P-selectin to human resting
      and activated platelets. In contrast, KPLI (a leukocyte adhesion blocking MoAb to
      PSGL-1) did not neutralize the binding of P-selectin to human platelets, even
      though it abolished the binding of P-selectin to human promyeloid HL-60 cells.
      Our results thus indicate that the 28-kDa glycoprotein may function as an
      important platelet ligand for P-selectin.

PMID- 12008956
TI  - Two regions of the human platelet F11-receptor (F11R) are critical for platelet
      aggregation, potentiation and adhesion.
AB  - The F11 receptor (F11R) was first identified on the surface of human platelets as
      a target for a stimulatory monoclonal antibody (M.Ab.F11) that induces secretion,
      followed by exposure of fibrinogen receptors and aggregation. Cloning of the gene
      of F11R has revealed that this protein is a cell adhesion molecule (CAM), a
      member of the Ig superfamily and an ortholog of the murine protein called
      junctional adhesion molecule (JAM). The present study has identified two domains
      through which M.Ab.F11 triggers a platelet response culminating with aggregation.
      M.Ab.F11-mediated platelet adhesion, and the potentiation of collagen and ADP
      induced platelet aggregation by M.Ab.F11, were found to involve the same two
      domains. A F11R recombinant protein (sF11R) completely inhibited platelet
      aggregation, adhesion and potentiation induced by M.Ab.F11, indicative that the
      active conformation of the external domain of F11R is present in the soluble,
      secreted recombinant protein. Furthermore, a specific peptide containing the
      sequence of the N-terminal amino acids S-1 to C-23 of F11R, and a peptide with
      the sequence of K-70 to C-82 in the 1st immunoglobulin-like (Ig) fold of F11R,
      both inhibited M.Ab.F11-induced aggregation, adhesion and potentiation of the
      aggregation of human platelets. Modeling of the 3D structure of the extracellular
      domain of the human platelet F11R suggests that these two regions form an active
      site within the conformation of this CAM. The sequence of these functional
      domains of F11R (in the N-terminus and 1st Ig-fold) provide the basis for new
      drug development in the treatment of certain types of thrombocytopenia and
      inflammatory thrombosis.

PMID- 12008957
TI  - Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as
      revealed by a patient with Hermansky-Pudlak syndrome.
AB  - Individuals with Hermansky-Pudlak Syndrome (HPS) lack platelet dense granules and
      have no ADP-autocrine response. Despite these platelet deficiencies, HPS patients
      exhibit a surprisingly mild bleeding phenotype. We hypothesize that activation of
      the PAR4 thrombin receptor compensates for the lack of an ADP-autocrine response
      by the P2Y12 ADP receptor in individuals with HPS. Here, we determine that PAR4
      activation by thrombin occurs well after ADP release from dense granules in
      normal individuals. However, the signal from PAR4 stabilizes platelet-platelet
      aggregate formation in the absence of P2Y12 activation by ADP. Thus, the strong
      signal emanating from PAR4 during platelet aggregation would provide an
      explanation for the mild bleeding diathesis of HPS.

PMID- 12008958
TI  - Brain-derived neurotrophic factor is stored in human platelets and released by
      agonist stimulation.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family,
      plays critical roles in the survival, growth, and maintenance of brain and
      peripheral neurons. We report the presence of BDNF protein in human platelets and
      its release upon agonist stimulation. The BDNF content of washed platelets varied
      widely, from 3.5 to 67 ng/4 x 10(8) platelets, averaging 25.2 +/- 21.2 ng/4 x
      10(8) platelets (mean+/-SD). The BDNF concentration in platelet-poor plasma was
      low (1.7+/-1.7 ng/ml, n = 11). Thrombin, collagen, the Ca++ ionophore A23187, and
      shear stress each induced a rapid release of BDNF from platelets. Up to only half
      of platelet BDNF was secreted upon agonist stimulation, suggesting that platelets
      may have a non-releasable pool of BDNF, or that the released BDNF binds to a
      recognition site on the platelet surface and is internalized, as occurs with
      serotonin. However, the cognate BDNF receptor, TrkB, was not detected in
      platelets. Nevertheless, the ability of BDNF to bind washed platelets was shown
      by FACS analysis confocal microscopy and by the binding and apparent
      internalization of [125I]-BDNF by platelets. A very high affinity site (Kd = 130
      x 10(-15) M, approximately 80 sites/platelet) and a moderately high affinity site
      (Kd = 20 nM, approximately 3750 sites/platelet) were identified. The BDNF content
      in two megakaryocytic cell lines, DAMI and Meg-01, was only 0.1% of the content
      measured in platelets. No BDNF mRNA was detected by Northern blotting in these
      cell lines or in platelets. The pituitary gland was also ruled out as a source
      for platelet BDNF, since the BDNF content of rat platelets did not decrease 2
      weeks after hypophysectomy. Thus, platelet BDNF is not acquired from the
      megakaryocyte or pituitary gland, but is probably acquired from other sources via
      the blood circulation. Platelets appear to bind, store and release BDNF upon
      activation at the site of traumatic injury to facilitate the repair of peripheral
      nerves or other tissues that contain TrkB.

PMID- 12008959
TI  - Evidence for anticoagulant activity and beta2-GPI accumulation in late endosomes
      of endothelial cells induced by anti-LBPA antibodies.
AB  - This investigation was undertaken to test whether anti-LBPA antibodies and IgG
      from patients with APS interfere with intracellular beta2GPI distribution in
      EAhy926 endothelial cells and with the coagulation system. Cell incubation with
      anti-LBPA MoAb or with patients' IgG resulted in antibody binding to late
      endosomes and caused beta2GPI redistribution and accumulation within perinuclear
      vesicular structures reminiscent of late endosomes. This finding suggests that
      aPI may contribute to the pathogenic mechanisms of APS by modifying the
      intracellular traffic of proteins, by interactions between aPl and LBPA, beta2GPI
      and/or LBPA-beta2GPI complexes. The anticoagulant activity of anti-LBPA MoAb was
      analyzed in a sensitized activated partial thromboplastin time (aPTT) system and
      in a dilute Russell's viper venom time (dRVVT). A significant, concentration
      dependent effect of the antibody on both aPTT and dRVVT prolongation was found.
      These observations suggest that LBPA is an important lipid target for aPl with
      potential functional implications for the immunopathogenesis of APS.

PMID- 12008960
TI  - Fibrinogen adsorption, platelet adhesion and thrombin generation at heparinized
      surfaces exposed to flowing blood.
AB  - Thrombus formation at an artificial surface in contact with blood is a complex
      process that encompasses accretion of platelets from flowing blood and fibrin
      deposition. Platelet adhesion and fibrin formation are intimately intertwined
      reactions that are triggered by different sets of surface adsorbed plasma
      proteins. To dissect the contribution of protein adsorption and platelet adhesion
      to thrombin formation, a coherent study was performed with non-coated (NC) and
      heparin-coated (HC) surfaces. Thrombin production in whole blood, platelet
      adhesion and protein adsorption were studied using an amidolytic thrombin assay,
      a dynamic platelet adhesion assay and ellipsometry, respectively. Thrombin
      generation in flowing whole blood exposed to HC surfaces was greatly diminished
      when compared with NC surfaces. However, separate platelet adhesion and protein
      adsorption studies with anticoagulated whole blood revealed that platelets do not
      adhere because fibrinogen is not available in the protein layer that was
      deposited during the perfusion. These findings indicate that the in vitro
      thrombogenicity of a material cannot be predicted from platelet adhesion and
      protein adsorption data when these measurements are performed with anti
      coagulated blood or platelet rich plasma. Preincubation of NC and HC surfaces
      with fibrinogen or 2000-fold diluted plasma resulted in similar amounts of
      surface-bound fibrinogen and mediated massive platelet adhesion from flowing
      whole blood. These results indicate that a) platelet adhesion correlates with the
      availability of surface-bound fibrinogen and b) NC and HC surfaces are
      indistinguishable with respect to protein (fibrinogen) adsorption and platelet
      adhesion. It is apparent that the heparinized surface used in our studies exerts
      its anti-thrombogenic properties by neutralizing locally formed thrombin and not
      by reducing fibrinogen-dependent platelet adhesion.

PMID- 12008961
TI  - Cholesterol-induced thrombogenicity of the vessel wall: inhibitory effect of
      fluvastatin.
AB  - High cholesterol levels are a known risk factor for coronary events. The
      molecular links between high serum cholesterol and the increased thrombogenicity
      of the arterial wall are still matter of investigation. In the present study we
      investigate the relationship between plasma cholesterol, thrombus formation and
      TF expression in a atherosclerotic rabbit model. Hypercholesterolemic rabbits
      showed a pronounced TF staining as well as NF-kappaB activation in the aortic
      arch. A consistent vessel wall platelet deposition was also observed. Treatment
      with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-kappaB
      activation, and platelet deposition (-56%). In vitro studies showed that the drug
      upregulated IkappaB alpha in unstimulated as well as in TNFalpha-stimulated cells
      and also impaired the TNFalpha-induced Cdc42 prenylation, indicating that
      fluvastatin interferes with the transcriptional activation of TF gene. These
      results indicate that the prothrombotic phenotype of arterial wall, associated
      with elevated serum cholesterol levels, is mediated by TF overexpression.
      Fluvastatin treatment reduces the prothrombotic tendency by inhibiting TF
      synthesis.

PMID- 12008962
TI  - Identification of critical residues for ligand binding in the integrin beta3 I
      domain by site-directed mutagenesis.
AB  - To define the structural basis of ligand recognition by alphaIIb beta3, we
      conducted site-directed mutagenesis of residues located on the top surface of the
      beta3 I-domain that is homologous to the I-domain of several alpha subunits and
      contains a putative ligand binding site. Here we identify D158 and N215 in beta3
      as novel residues critical for ligand binding. Alanine substitution of D158 or
      N215 abolished binding of a ligand-mimetic antibody and fibrinogen to alphaIIb
      beta3 induced by different types of integrin activation. CHO cells expressing
      recombinant alphaIIb beta3 bearing D158A or N215A mutation did not adhere to
      fibrinogen. These mutations had the same effect on ligand binding to another
      beta3 integrin, alphaVbeta3. Compared to the alphaI-domain structure, the betaB
      betaC loop containing D158 in the beta3 I-domain is quite different in length and
      sequence. These results suggest that the structure for ligand recognition is
      different in the betaI- and alphaI-domains.

PMID- 12008963
TI  - Definitions in biorheology: cell aggregation and cell adhesion in flow.
      Recommendation of the Scientific Subcommittee on Biorheology of the Scientific
      and Standardisation Committee of the International Society on Thrombosis and
      Haemostasis.

PMID- 12008964
TI  - What is the risk of withholding anticoagulation in those with a low probability
      ventilation perfusion scan in the investigation of pulmonary emboli?

PMID- 12008965
TI  - Prevalence of the 23bp endothelial protein C receptor (EPCR) gene insertion in
      the Irish population.

PMID- 12008966
TI  - FXI is essential for thrombus formation following FeCl3-induced injury of the
      carotid artery in the mouse.

PMID- 12008967
TI  - How to get fat: nutritional mechanisms of seasonal fat accumulation in migratory
      songbirds.
AB  - Many migratory birds accumulate large amounts of lipids as the prime energy
      source for their long-distance flights. This fat accumulation is mostly under
      endogenous control, reflecting genetically programmed temporal shifts of the body
      mass set point. It is accompanied by an increase in daily food intake and food
      utilisation efficiency and by a seasonal shift in food selection. In particular,
      seasonal frugivory appears to play a key role in many migrants. Fruits have a
      high content of fatty acids indispensable for building up the specific depot
      lipids. In addition, plant secondary compounds seem to play some kind of
      supportive role, but the mechanisms are not yet known. The effect of being fat on
      the metabolic situation in migrant birds appears to be similar to the metabolic
      syndrome in obese humans. The fat migratory bird provides a model through which
      to study nutritional factors as well as the biochemical and endocrine regulation
      of food intake, body mass and obesity.

PMID- 12008968
TI  - Occurrence, functions and biosynthesis of polyamides in microorganisms and
      biotechnological production.
AB  - Microorganisms are able to synthesize three different polyamides by enzymatic
      processes independently from ribosomal protein biosynthesis: poly(gamma-D
      glutamic acid), poly(epsilon-L-lysine) and multi-L-arginyl-poly(L-aspartic acid)
      which is also referred to as cyanophycin. These polyamides, which occur mainly in
      Bacillus spp. (and only a few other eubacteria and the nematocysts of Cnidaria,
      in Streptomyces albulus or in cyanobacteria, respectively), have recently
      attracted considerable interest of the chemical industry and may be suitable for
      various applications. This review summarizes our current knowledge on the
      occurrence, biosynthesis, physiological functions, and biodegradation as well as
      on the properties and putative applications of these polyamides. Emphasis is
      placed on the enzymology of the polymerization and on the genes encoding the
      polymerizing enzymes, which have only recently become available for cyanophycin
      synthetases. Prospects for novel production processes. in particular for
      cyanophycin, are also presented.

PMID- 12008969
TI  - Relevance of mangroves for the production and deposition of organic matter along
      tropical continental margins.
AB  - Mangroves are highly complex ecosystems occupying a major part of tropical
      coastlines. High primary productivity, efficient biological nutrient recyling and
      a permanent exchange with terrestrial and marine ecosystems are their common
      features. Despite the high production and export rates of leaf litter, mangrove
      detritus has been reported to be of minor importance in sustaining marine food
      webs. The geographical distribution of mangrove-derived organic matter (OM) in
      marine sediments is found to be restricted to the vicinity of its source.
      Dissolved nutrient inputs from mangroves and rivers may fuel the production of
      marine OM. In this paper we assess the relevance of mangroves for the production
      and sedimentation of OM in the tropical coastal ocean based on data available
      from the literature and our own research results. We estimate the rates of carbon
      accumulation in mangrove sediments and of carbon export to the coastal seas. From
      the rates of litter fall and export we calculate carbon accumulating in mangrove
      sediments to be in the order of 23x10(12) g C per year and mangrove carbon
      introduced into the coastal ocean to be in the order of 46x10(12) g C per year.
      They account for about 11% of the total input of terrestrial carbon into the
      ocean and 15% of the total carbon accumulating in modern marine sediments.

PMID- 12008970
TI  - Differential anti-lipid peroxidative activity of melatonin.
AB  - Scavenging activities of melatonin, which is a pineal secretory product and
      functions in circadian biology, and its related compounds against reactive oxygen
      species such as superoxide anion radical, hydrogen peroxide, hydroxyl radical and
      singlet oxygen as well as organic peroxide radical (t-BuOO*) were evaluated
      chemically by using electron spin resonance-spin trap and chemiluminescence
      methods. Antioxidative activity of the compounds was estimated by IC50 value
      (microM), 50% inhibiting concentration of a compound against reactive oxygen
      species formed in each system, and the second-order rate constants (k2) for the
      reactions of the compounds and superoxide anion radical or hydroxyl radical.
      Because melatonin has exhibited the highest scavenging activity against t-BuOO*,
      the biochemical anti-lipid peroxide radical scavenging activities of melatonin
      were examined. We found that melatonin exhibits higher anti-lipid peroxidative
      activity in the rat brain microsomes than in the rat liver microsomal and
      liposomal systems, suggesting that melatonin may function as a treatment for
      reactive oxygen species-related diseases of the brain.

PMID- 12008971
TI  - Largest bird from the Early Cretaceous and its implications for the earliest
      avian ecological diversification.
AB  - With only one known exception, early Cretaceous birds were smaller than their
      closest theropod dinosaur relatives. Here we report on a new bird from the Early
      Cretaceous feathered-dinosaur-bearing continental deposits of Liaoning, northeast
      China, which is not only larger than Archaeopteryx but is nearly twice as large
      as the basal dromaeosaur Microraptor. The new taxon, Sapeornis chaoyangensis gen.
      et sp. nov., has a more basal phylogenetic position than all other birds except
      for Archaeopteryx. Its exceptionally long forelimbs, well-developed deltoid crest
      of the humerus, proximally fused metacarpals, relatively short hindlimbs and
      short pygo-style indicate powerful soaring capability and further suggest that by
      the Early Cretaceous ecological diversification of early birds was greater than
      previously assumed. Electronic supplementary material to this paper can be
      obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00114-001-0276-9.

PMID- 12008972
TI  - Cells of the connective tissue differentiate and migrate into pollen sacs.
AB  - In angiosperms, archesporial cells in the anther primordium undergo meiosis to
      form haploid pollen, the sole occupants of anther sacs. Anther sacs are held
      together by a matrix of parenchyma cells, the connective tissue. Cells of the
      connective tissue are not known to differentiate. We report the differentiation
      of parenchyma cells in the connective tissue of two Gordonia species into pollen
      like structures (described as pseudopollen), which migrate into the anther sacs
      before dehiscence. Pollen and pseudopollen were distinguishable by morphology and
      staining. Pollen were tricolpate to spherical while pseudopollen were less rigid
      and transparent with a ribbed surface. Both types were different in size, shape,
      staining and surface architecture. The ratio of the number of pseudopollen to
      pollen was 1:3. During ontogeny in the connective tissue, neither cell division
      nor tetrad formation was observed and hence pseudopollen were presumed to be
      diploid. Only normal pollen germinated on a germination medium. Fixed
      preparations in time seemed to indicate that pseudopollen migrate from the
      connective tissue into the anther sac.

PMID- 12008973
TI  - Estimation of soil erosion and deposition rates at an agricultural site in
      Bavaria, Germany, as derived from fallout radiocesium and plutonium as tracers.
AB  - In the near future, the use of 137Cs from global fallout (Cs) as a tracer for
      erosion studies will no longer be possible in areas with a substantial deposition
      of Chernobyl-derived 137Cs. Therefore, we have used (239+240)Pu from global
      fallout (Pu) as a tracer as well as 137Cs in order to determine long-term soil
      redistribution rates for an agricultural field (inclination about 20%, area
      approx. 3 ha) in Scheyern, Bavaria. The mean erosion and deposition rates derived
      from Cs were -37 and +52 t x ha(-1) x year(-1), respectively; those from Pu were 
      32 and +39 t x ha(-1) x year(-1). We found no statistical difference between the
      means obtained by the two tracers. In contrast to Pu, however, the rates obtained
      by Cs were not accurate enough to assure the presence of a net soil
      redistribution. Modeling of soil translocation in the field by water and tillage
      erosion resulted in estimates which were in reasonable agreement with the rates
      derived from Pu.

PMID- 12008974
TI  - Zinc nutritional status in obese children and adolescents.
AB  - Studies in animals and humans have corroborated that zinc (Zn) metabolism is
      altered in obesity. The present work intends to evaluate the Zn nutritional
      status in obese children and adolescents by the determination of some biochemical
      parameters and analyses of the diets. The investigation was carried out in a
      group of obese children and adolescents (n = 23) and compared to a control group
      (n = 21), both between 7 and 14 yr of age. A software analyzed diet information
      from 3-d food records. Body composition was evaluated by body mass index,
      bioelectrical impedance, and skinfold measurements. Zinc nutritional status was
      evaluated by Zn determination in plasma, erythrocyte, and 24-h urine, by atomic
      absorption spectrophotometry (lambda = 213.9 nm). Diets consumed by both groups
      had marginal concentrations of zinc. Zinc concentrations in plasma and
      erythrocytes were significantly lower in the obese group. Urinary zinc excretion
      was significantly higher in the same group. The results allowed one to conclude
      that zinc nutritional status in obese individuals is altered.

PMID- 12008975
TI  - Immunoregulatory and antioxidant performance of alpha-tocopherol and selenium on
      human lymphocytes.
AB  - The role of alpha-tocopherol (alpha-toco) and selenium (Se) on human lymphocyte
      oxidative stress and T-cells proliferation were studied by flow cytometry. We
      measured the hydrogen peroxide and glutathione levels in cultured human T
      lymphocytes and the proliferation of their subsets: T-helper/inducer, T
      suppressor/cytotoxic, and natural killer and interleukin-2 receptors upon
      stimulation by the mitogens phytohemaglutinin (PHA) and lipopolysaccharide (LPS).
      The results indicate that early stimulation by mitogens is affected by the
      glutathione and hydrogen peroxide status of the T-lymphocytes. The addition of
      100 microM or 500 microM alpha-toco or 0.5 microM Se alone shows weak antioxidant
      and immunostimulant properties. When combined, an enhanced antioxidant and
      immunoregulatory effect was observed. The present findings indicate that alpha
      toco and Se have interactive effects as oxygen radical scavengers, thus promoting
      human lymphocyte response to antigens. This suggests that micronutrient status is
      an important factor in considering when interpreting the results of in vitro
      assays of lymphocyte function.

PMID- 12008976
TI  - Determination of some elements in the cervical mucus of healthy Taiwanese women,
      by GF-AAS.
AB  - The levels of seven trace elements such as copper, iron, zinc, selenium, cadmium,
      chromium, and nickel were determined by graphite furnace-atomic absorption
      spectrometry in the cervical mucus of 45 women residing in Taiwan, Republic of
      China. These women were in good health and had no precancerous or cancerous
      lesions on their cervix. The women were separated into four age groups to
      establish if there was a relationship between the age of the subjects and the
      values of these elements in the cervical mucus. By one-way analysis of variance,
      significant differences in the selenium and nickel concentrations were found
      among the four age groups (p < 0.05). The mean concentration of selenium in each
      age group was significantly higher for the older women. A significant correlation
      between age and selenium concentration was found by linear regression (r = 0.23,
      p = 0.00048). No significant differences among the concentrations of copper,
      iron, zinc, cadmium, and chromium were found among these four age groups (p >
      0.05). The results presented in this work may be considered as baseline values
      for these elements in the cervical mucus of healthy Taiwanese women for use as
      reference in studies on cervical diseases and tissue damage.

PMID- 12008977
TI  - Alteration of trace element distribution and testis ACE activity in mice with
      high peritoneal aluminum.
AB  - The present investigation was conducted to assess the effects of subacute
      aluminum (Al) exposure on testicular zinc (Zn), copper (Cu), and iron (Fe)
      distribution in mice. Animals were intraperitoneally exposed to 0, 13, or 35 mg
      Al/kg body weight/d for a period of 14 d. Al concentrations in serum and testis
      in Al-treated animals were significantly higher than those of controls. The serum
      concentrations of Fe were lower, whereas serum Zn and Cu showed a pattern
      comparable to that of controls. The accumulation of testicular Fe and Cu
      remarkably increased in Al-exposed groups, whereas the Zn concentration in testis
      was significantly reduced only at the highest dose of Al exposure. The values of
      testicular thiobarbituric acid reactive substances (TBARS) were also increased
      after Al administration, indicating increased lipid peroxidation and oxidative
      stress. In addition, when the testicular Al was increased, the testis-specific
      angiotensin-converting enzyme (testis ACE) was noted. The results of this study
      indicated that part of the effect of Al intoxication on testis might contribute
      to abnormal metabolism of other minerals, such as Fe, Zn, and/or Cu. It was also
      suggested that reduced testis ACE activity presumably plays an important role in
      oxidative damage of Al-induced testicular toxicity.

PMID- 12008978
TI  - Effect of Al(III) on surface properties of Bifidobacterium thermophilum as a
      function of temperature.
AB  - The effects of Al(III) on surface properties and lactate accumulation by
      Bifidobacterium thermophilum were investigated. Bacteria were treated with
      Al(III) at 37 degrees C and 4 degrees C, then exposed to free radicals or nisin.
      When exposed to Al(III) at 37 degrees C, the organism exhibited spreading on
      hydrophobic surfaces and showed high susceptibility to free-radical alteration as
      indicated by Fe(III) binding, but showed little effect on lactate production in
      the presence or absence of nisin, even after washing with 2 mM EDTA. At 4 degrees
      C, there was no increased surface spreading or binding of Fe(III), but protection
      against nisin action was present. This, however, was abolished after washing with
      EDTA. It was concluded that membrane fluidity is required to affect membrane
      lipid rearrangement, resulting in surface spreading and increased susceptibility
      to peroxidation, whereas only loose binding of Al(III) to membrane surfaces is
      sufficient to prevent transmembrane channel formation by nisin.

PMID- 12008979
TI  - Microcalorimetric study of the action of Ce(III) ions on the growth of E. coli.
AB  - A microcalorimetric technique based on bacterial heat output was used to evaluate
      the action of Ce(III) ions on the growth of Escherichia coli. The power-time
      curves of the growth metabolism of the bacteria were studied in the presence and
      absence of Ce(III) by means of a LKB-2277 Bioactivity Monitor, by a stopped-flow
      method at 37 degrees C. For evaluation of the results, the maximum power, Pmax,
      the growth rate constant k, and the heat effects Qlog, Qstat, and Qtot for the
      log phase, the stationary phase, and total heat output, respectively, were
      determined. For comparison, a spectrophotometer was used to estimate the number
      of cells in the liquid culture. The shape of the bacteria was examined by
      electron microscopy. We concluded that the presence of cerium ions at
      concentrations below 350 microg/mL have a stimulatory effect on the growth of E.
      coli, whereas concentrations at or above 400 microg/mL may have an inhibitory
      effect.

PMID- 12008980
TI  - Antimutagenic activity of selenium-enriched green tea toward the heterocyclic
      amine 2-amino-3-methylimidazo[4,5-f]quinoline.
AB  - Both selenium and green tea have been reported to exhibit antigenotoxic and
      cancer chemopreventive properties. We compared the antimutagenic activities of
      regular green tea and selenium-enriched green tea obtained from Hubei Province,
      China, toward the heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline
      (IQ) in the Salmonella assay. Selenium-enriched green tea obtained by foliar
      application of selenite exhibited concentration-dependent inhibition of IQ
      induced mutagenesis in the presence of rat liver S9 and was significantly more
      effective than regular green tea tested under the same conditions. Analytical
      studies revealed no major differences in the polyphenol or caffeine content
      between regular green tea and selenium-enriched green tea, but the latter tea
      contained approximately 60-fold higher concentrations of selenium compared with
      regular green tea. The only soluble form of selenium was identified as selenite.
      The antimutagenic effects of certain individual tea constituents, such as
      epicatechin gallate and catechin, were enhanced by the addition of selenite to
      the Salmonella assay. Sodium selenite, sodium selenate, seleno-DL-cysteine,
      seleno-L-methionine, and L-Se-methylselenocysteine were not antimutagenic toward
      IQ when tested alone, but augmented significantly the inhibitory potency of green
      tea. The results suggested an enhancing ("coantimutagenic") effect of selenium in
      combination with green tea in vitro, but in vivo studies are needed to assess
      whether there is a synergistic effect of tea and selenium to protect against
      heterocyclic amine-induced mutagenesis and carcinogenesis.

PMID- 12008981
TI  - Some essential elements in maternal and cord blood in relation to birth weight
      and gestational age of the baby.
AB  - Maternal and cord blood were collected from 54 Indian women at parturition and
      analyzed for Zn, Cu, and Fe by flame atomic absorption spectrophotometry to
      determine the relationship between levels of these elements in mother's and
      infant's blood and maternal age, birth weight, and gestational age of the baby.
      The blood Zn level of mothers in the age group 24-28 yr was significantly higher
      than those of mothers in the age group of 18-23 yr (p<0.05). Similarly, mothers
      in the 24 to 28-yr group also had higher blood Fe level than mothers in the group
      29-38 yr (p<0.05). The levels of Zn, Cu, and Fe were higher in the maternal blood
      and lower, but not significantly, in the cord blood of low-birth-weight babies
      than in those of normal-birth-weight babies. However, differences in the levels
      of Zn, Cu, and Fe between maternal and cord blood of the two birth-weight groups
      was statistically significant. There were no significant differences in the
      levels of the three elements in maternal or cord blood by the gestational age of
      the baby. A weak but significant correlation was found between the birth weight
      of the baby and the Fe level in the cord blood (r=0.26; p<0.05). Also, weak
      significant correlations were observed between gestational age of the baby and Fe
      (r=0.23; p<0.05) and Cu (r=0.31; p<0.05) levels in the cord blood. Although,
      there are many confounders of low birth weight and preterm deliveries, a
      diminished placental transfer of these essential elements could be one of the
      several etiological factors for low birth weight of newborns.

PMID- 12008982
TI  - Community-based nutrition program aims message at African American females.

PMID- 12008983
TI  - Mycoprotein: is America ready for a meat substitute derived from a fungus?

PMID- 12008984
TI  - The new IRS weight-loss deduction: what it means to dietetics professionals.

PMID- 12008985
TI  - European "gluten-free" solid foods for infants may be a risky food for celiacs.

PMID- 12008986
TI  - The obesity epidemic: what's being done?

PMID- 12008987
TI  - Family-based interventions for the treatment of childhood obesity.

PMID- 12008988
TI  - Nutrition therapy and eating disorders: what is the correct calorie level for
      clients with anorexia?

PMID- 12008989
TI  - A cost-analysis of adopting a healthful diet in a family-based obesity treatment
      program.
AB  - OBJECTIVE: To assess dietary costs during a family-based pediatric obesity
      intervention. DESIGN: Families were randomized to one of two groups. Dietary and
      cost data were collected from a parent or child using three 24-hour recalls: at
      baseline, 6 months, and 12 months. SUBJECTS: Thirty-one families with an obese 8-
      to 12-year-old child entered treatment, with complete dietary data provided from
      20 families. INTERVENTION: The 20-week behavior modification intervention
      emphasized increasing diet nutrient-density. Families attended group and
      individual sessions or group sessions. MAIN OUTCOME MEASURES: Energy intake;
      percent of energy from protein, fat, and carbohydrate; servings and percent
      servings from food groups classified by nutrient density; and daily food costs.
      STATISTICAL ANALYSES PERFORMED: Mixed analyses of variance, with group as the
      between-subject factor, and time as the within-subject factor. RESULTS: No
      significant effect of group was found in any analyses. Significant decreases in
      percent overweight were observed at 6 and 12 months for children (-10.0+/-8.7 and
      -8.0+/-10.3, respectively) (mean+/-standard deviation) and parents (-6.7+/-10.3
      and -5.3+/-14.1). Energy intake for parents and children combined significantly
      decreased from baseline (1,881+/-462) to 6 months (1,412+/-284), and 1 year
      (1,338+/-444). Servings from low-nutrient-dense foods significantly decreased
      from baseline (34.7+/-16.2) to 6 months (16.0+/-8.6) and 1 year (18.6+/-9.2),
      causing a significant increase in diet nutrient density. Dietary cost did not
      change at 6 months, but significantly decreased from baseline to 1 year ($6.77+/
      2.41 to $5.04+/-1.80). Cost per 1,000 kcal did not significantly change.
      APPLICATIONS/CONCLUSIONS: Adopting a lower-energy, nutrient-dense diet did not
      increase dietary costs over time. Consequently, cost should not be a barrier in
      the adoption of a healthful diet.

PMID- 12008990
TI  - Home and eating environments are associated with saturated fat intake in children
      in rural West Virginia.
AB  - OBJECTIVE: To describe sociodemographic, environmental, and knowledge factors in
      relation to self-reported, energy-adjusted saturated fat consumption among
      children in rural West Virginia. PARTICIPANTS: Three hundred twenty-five 5th
      graders who participated in the Coronary Artery Risk Detection in Appalachian
      Communities Project conducted in 3 rural counties in West Virginia in 1998-1999.
      METHODS: A cross-sectional survey based on self-reported information collected
      using a food frequency questionnaire, a nutrition knowledge questionnaire, and a
      family composition questionnaire. STATISTICAL ANALYSES: Descriptive statistics
      and multiple linear regression analysis. RESULTS: The mean percentage of energy
      from total fat was 31.8% +/- 4.9 and from saturated fat was 11.8% +/- 2.3. Energy
      adjusted saturated fat intake was significantly higher among children with higher
      frequencies of breakfast and late-night snacks prepared away from home, and in
      households with single mothers. Variables associated with higher energy-adjusted
      saturated fat intake with marginal statistical significance (P=.05-.10) included
      attendance at schools with a higher percentage of students receiving free or
      reduced-price lunch, usual breakfast location other than home or school, and less
      knowledge about low-fat, low-sodium foods. Frequent late-night snacks prepared
      away from home and living with single mothers remained as significant correlates
      of energy-adjusted saturated fat intake independent of other hypothesized
      determinants. CONCLUSION: Efforts to reduce saturated fat intake among children
      in rural areas should focus on food prepared away from home. Nutrition-related
      behaviors of single mothers should be explored further.

PMID- 12008991
TI  - Behavior change outcomes in an outpatient cardiac rehabilitation program.
AB  - OBJECTIVE: To evaluate the effectiveness of nutrition education within an
      outpatient cardiac rehabilitation program. DESIGN: Subjects were assigned,
      according to participation in cardiac rehabilitation programs in two community
      hospitals within an integrated healthcare system, to either a treatment (n=54),
      or a control group (n=50). SUBJECTS/SETTING: One hundred four men and women, age
      range 35 to 85 years, participating in a 6-week cardiac rehabilitation program.
      Most were men (80%) and overweight. The majority presented with the diagnosis of
      myocardial infarction followed by coronary artery bypass surgery or percutaneous
      transluminal coronary angiography procedure. INTERVENTION: Subjects in the
      control group received usual nonindividualized nutrition education from cardiac
      rehabilitation therapists. Subjects in the treatment group attended two group
      nutrition education classes and one individual diet counseling session, all led
      by the same dietitian. MAIN OUTCOME MEASURES: Changes in fat, saturated fat,
      cholesterol, and carbohydrate intake, and restaurant eating habits as assessed by
      the Diet Habit Survey; changes in cardiac diet self-efficacy; and changes in
      health-related quality of life. Statistical analyses performed Group-by-time
      analysis of variance with repeated measures, chi2 test. RESULTS: The treatment
      group had greater improvement in Restaurant and Recipes scores on the Diet Habit
      Survey (2.6 vs 1.0) and a greater cardiac diet self-efficacy mean score (4.3)
      compared with the control group (3.8), with the greatest change in items related
      to eating in restaurants, away from home, or when alone. From entry into the
      program to discharge, the cholesterol-saturated fat index decreased significantly
      in the control group (from 57 to 48), and in the treatment group (from 51 to 42).
      The percent of energy from carbohydrate increased significantly in the control
      group (from 51% to 55%) and in the treatment group (from 53% to 57%). There were
      no differences between groups over the 3 time periods (baseline, 6 weeks, and 3
      month follow-up) (n=39 for control group and n=47 for treatment group for all 3
      time periods). APPLICATIONS/CONCLUSIONS: Nutrition education within an outpatient
      cardiac rehabilitation program can improve dietary choices at restaurants and
      boost self confidence in the ability to adhere to a lipid-lowering diet.

PMID- 12008992
TI  - Half of rural girls aged 8 to 17 years report weight concerns and dietary
      changes, with both more prevalent with increased age.
AB  - OBJECTIVE: Determine body image satisfaction, weight concerns and dieting
      behaviors, Tanner index, and dietary adequacy in young women and girls. DESIGN: A
      cross-sectional, self-selected comparative survey was completed.
      SUBJECTS/SETTING: Rural white women and girls (N=333) aged 8 to 17 years,
      completed a weight concerns and dieting behavior questionnaire, a body image
      assessment, and a self-rating of sexual maturity, and 230 subjects completed 3
      day diet diaries. ANALYSES PERFORMED: Correlational analysis identified
      relationships between variables among age groups (8 to 10 years, 11 to 14 years,
      and 15 to 17 years). Analysis of variance examined differences among variables.
      Multiple regression analysis measured the influence of variables on diet quality.
      A mean adequacy ratio (MAR) was computed to express dietary adequacy. RESULTS:
      More than half (52%) of the subjects reported 1 or more weight concerns and
      dieting behaviors. This pattern increased with age. Friends dieting positively
      influenced scores (P=.0001) for 8- to 14-year olds, and a dieting family member
      meant higher scores (P=.04) for all ages studied. Although most wanted to be
      smaller, there was little body image dissatisfaction. Girls (aged 11 to 17 years)
      who dieted had greater body dissatisfaction (P=.0001) and significantly lower
      (P=.002), but adequate diets (MAR=76) compared to those who did not diet
      (MAR=81). Inverse relationships were found for the 11- to 14-year olds with diet
      adequacy and the following variables: body image dissatisfaction (-2.7, P<.01)
      and weight concerns and dieting behaviors (-3.7, P<.001). These variables
      accounted for 34% (P=.0001) of the variance in the MAR. APPLICATIONS/CONCLUSIONS:
      Dietitians, partnering with school and health clinic personnel, need to educate
      girls younger than age 11 years about attaining the dietary adequacy needed to
      support expected growth. This age is important because it appears that actual
      weight and dieting concerns begin earlier, and by age 11 years, negatively affect
      diet quality.

PMID- 12008993
TI  - Mothers' attitudes toward nutrition are related to daughters' but not to sons'
      plasma cholesterol levels.
AB  - OBJECTIVE: To examine the relationship between parents' attitudes toward
      nutrition and plasma lipid levels of their children. DESIGN: Parents' nutrition
      attitudes were assessed with the Nutritional Attitude Scale, a self-report
      questionnaire measuring attitudes toward the adoption of a low-fat, low
      cholesterol diet. Parents' and children's plasma lipid and lipoprotein levels
      were obtained. Data were collected during the baseline period and a 1-year follow
      up of the Family Heart Study, a small community study of cholesterol-lowering via
      dietary change. PARTICIPANTS/SETTING: Participants were 33 girls and 34 boys
      (aged 6 to 13 years), and their parents. They were a subsample of European
      American, middle-class, Portland, Ore, families participating in the Family Heart
      Study. STATISTICAL ANALYSES: Associations between parents' nutrition attitudes
      and plasma lipid levels of their children were evaluated using multiple linear
      regression analyses, controlling for the contribution of parents' lipid levels to
      those of their children. RESULTS: Mothers' nutrition attitudes interacted with
      their daughters' ages, accounting for 14% of the variance in plasma total
      cholesterol level and 11% in low-density lipoprotein cholesterol level in their
      daughters. Mothers' unhealthful nutrition attitudes were associated with elevated
      levels of plasma total and low-density lipoprotein cholesterol levels among older
      daughters, but not among younger daughters nor their sons. Fathers' nutrition
      attitudes were unrelated to their children's plasma lipid levels. Mothers'
      nutrition attitudes assessed at baseline remained a significant predictor of
      their daughters' lipid levels measured 1 year later. APPLICATIONS/CONCLUSIONS:
      The previously reported relationships between adults' unhealthful nutrition
      attitudes and their own elevated plasma lipid levels appear to extend to that of
      their children. The association between mothers' nutrition attitudes and their
      daughters' lipid levels highlights the importance of focusing on nutrition
      attitudes when designing intervention programs to reduce plasma lipids and
      lipoproteins via dietary changes in the family.

PMID- 12008994
TI  - Tracking dietary intake in white and Mexican-American children from age 4 to 12
      years.
AB  - OBJECTIVE: To examine the tracking (ie, the stability over time) of dietary
      intake in Mexican-American and white children aged 4 to 12 years. SUBJECTS:
      Children 4 years of age (n=351) were assessed at baseline and 65% (n=228)
      completed the 8-year study. DESIGN: Cardiovascular disease-related dietary intake
      was defined as energy, percent of energy from fat, and sodium (mg/1,000 kcal).
      From age 4 to 7 years, a modified 24-hour recall with observation of lunch and
      dinner and interview of the primary food preparer for unobserved foods was used
      to describe dietary intake. For children aged 11 to 12 years, a standardized 24
      hour recall was used. STATISTICAL ANALYSES: A mixed effects model that adjusted
      for sex, ethnicity, and measurement wave allowed for separation of shorter-term
      variations in diet from more stable ("between subject") variations. Extent of
      between-subject variance is an indication of tracking. RESULTS: From age 4 to age
      7, there were statistically significant between-subject variance components for
      energy (P<.00001), percent of energy from fat (P<.00001), and sodium per 1,000
      kcals (P<.001); for ages 11 and 12, energy intake was significant (P<.00001).
      There were no significant associations for dietary intake from age 4 to 12 years.
      CONCLUSIONS/APPLICATIONS: It seems that dietary intakes are stable over short
      periods and at earlier ages compared with longer intervals and later ages.
      Nutrition interventions are needed in childhood and throughout adolescence.

PMID- 12008995
TI  - Use of cognitive interview techniques in the development of nutrition surveys and
      interactive nutrition messages for low-income populations.
AB  - The effectiveness of dietary surveys and educational messages is dependent in
      part on how well the target audience's information processing needs and abilities
      are addressed. Use of pilot testing is helpful; however, problems with wording
      and language are often not revealed. Cognitive interview techniques offer 1
      approach to assist dietitians in understanding how audiences process information.
      With this method, respondents are led through a survey or message and asked to
      paraphrase items; discuss thoughts, feelings, and ideas that come to mind; and
      suggest alternative wording. As part of a US Department of Agriculture-funded
      nutrition education project, 23 cognitive interviews were conducted among
      technical community college students in North Carolina. Interview findings
      informed the development of tailored computer messages and survey questions.
      Better understanding of respondents' cognitive processes significantly improved
      the language and approach used in this intervention. Interview data indicated 4
      problem areas: vague or ineffective instructions, confusing questions and
      response options, variable interpretation of terms, and misinterpretation of
      dietary recommendations. Interviews also provided insight into the meaning of
      diet-related stages of change. These findings concur with previous research
      suggesting that cognitive interview techniques are a valuable tool in the
      formative evaluation and development of nutrition surveys and materials.

PMID- 12008996
TI  - Frequency of binge eating disorder in an outpatient weight loss clinic.

PMID- 12008997
TI  - Psychological distress is associated with unhealthful dietary practices.

PMID- 12008998
TI  - Lifestyle-related weight gain in obese men with newly diagnosed obstructive sleep
      apnea.

PMID- 12008999
TI  - A low-fat afterschool snack improves the nutritional quality of elementary school
      children's diets.

PMID- 12009000
TI  - Foodservice systems management competencies of Korean dietitians: usage,
      perceived importance, and educational preparation.

PMID- 12009001
TI  - Position of the American Dietetic Association: ethical and legal issues in
      nutrition, hydration, and feeding.
AB  - It is the position of the American Dietetic Association that the development of
      clinical and ethical criteria for the nutrition and hydration of persons through
      the life span should be established by members of the health care team.
      Registered dietitians should work collaboratively to make nutrition, hydration,
      and feeding recommendations in individual cases. Registered dietitians have an
      active role in determining the nutrition and hydration requirements for
      individuals throughout the life span. When patients choose to forgo artificial
      nutrition and hydration, or when patients lack decision-making capacity, and
      others must decide whether or not to provide artificial nutrition and hydration,
      the registered dietitian has an active and responsible professional role in the
      ethical deliberation around that decision. There is strong clinical, ethical, and
      legal support both for and against the administration of food and water when
      issues arise regarding what is or is not wanted by the patient and what is or is
      not warranted by empirical clinical evidence. When a conflict arises, the
      decision to administer or withhold nutrition and hydration requires ethical
      deliberation. The registered dietitian's understanding of nutrition and hydration
      within the context of nutritional requirements and cultural, social,
      psychological, and spiritual needs provides an essential basis for ethical
      deliberation on issues of nutrition and hydration.

PMID- 12009002
TI  - Healthy weight for kids: Hertzler Fund kicks off the Family Nutrition and
      Physical Activity Screening Initiative.

PMID- 12009003
TI  - Protocols for identifying drug-nutrient interactions in patients: the role of the
      dietitian.

PMID- 12009004
TI  - Parathyroid hormone-related protein induced coupled increases in bone formation
      and resorption markers for 7 years in a patient with malignant islet cell tumors.
AB  - Parathyroid hormone-related protein (PTHrP) and PTH share the common PTH/PTHrP
      receptor. Although an elevated level of circulating PTHrP in patients with
      malignancies causes hypercalcemia as does PTH, chronic and systemic effects of
      PTHrP on bone metabolism in humans are not well understood because tumor-burden
      patients showing hypercalcemia usually have a poor prognosis. We investigated
      bone and calcium metabolism in a patient with malignant islet cell tumors showing
      hypercalcemia due to the elevated plasma PTHrP level for 7 years. Hypercalcemia
      and hypercalciuria continued throughout the clinical course in spite of frequent
      infusions of bisphosphonates. Bone resorption markers and a bone formation marker
      were consistently elevated as seen in primary hyperparathyroidism, a disease
      caused by an autonomous hypersecretion of PTH. Based on biochemical measurements
      including bone markers and serum 1,25-dihydroxyvitamin D, the clinical features
      of this case essentially are the same as those of primary hyperparathyroidism
      except for the elevated level of plasma PTHrP with suppressed intact PTH level.
      Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as
      well as calcium metabolism are indistinguishable from those of PTH in human.

PMID- 12009005
TI  - Hyperparathyroidism, humoral hypercalcemia of malignancy, and the anabolic
      actions of parathyroid hormone and parathyroid hormone-related protein on the
      skeleton.
AB  - So what have we learned from the Takeuchi case? It has been 80 years since
      malignancy-associated hypercalcemia was described. It has been 45 years since HHM
      was first described. It has been 15 years since PTHrP was identified, and 12
      years since PTHrP immunoassays became available for clinical research. We now
      know almost everything about HHM in pathophysiological terms, and we can
      reproduce the cardinal features of the syndrome in laboratory animals and humans.
      The Takeuchi case reminds us that we still have a few things to learn about HHM.
      Specifically, "Why is the regulation of 1,25(OH)2D different in patients with HHM
      and HPT?" and "Why is normal osteoblast-osteoclast coupling dysregulated in HHM?"
      or more fundamentally, "What regulates osteoblast-osteoclast coupling, and why is
      it deranged in HHM?" Given the rate of accumulation of new information about HHM,
      about the anabolic effects of PTH and PTHrP, and about osteoblast-osteoclast
      coupling over the past 10 years, there is reason to be optimistic that the
      answers to these questions will soon become clear.

PMID- 12009006
TI  - c-myc is required for osteoclast differentiation.
AB  - The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand
      (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation
      has been established clearly. However, the downstream signaling pathways
      activated by this cytokine remain largely unknown. To identify genes that play a
      role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system
      for the differentiation of multinucleated osteoclasts from mononucleated
      precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant
      osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific
      markers and were able to form resorption pits on both calcium phosphate films and
      bone slices. This system was used to identify genes that are regulated by RANKL
      and may play a role in osteoclast differentiation. The proto-oncogene c-myc was
      strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated
      cells. Expression of Myc partners Max and Mad, on the other hand, was constant
      during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7
      cells and were able to block RANKL-induced OCL formation. Northern Blot analysis
      revealed a delay and a significant reduction in the level of messenger RNA (mRNA)
      for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that
      c-myc is a downstream target of RANKL and its expression is required for RANKL
      induced osteoclastogenesis.

PMID- 12009007
TI  - Involvement of cyclo-oxygenase-2 in osteoclast formation and bone destruction in
      bone metastasis of mammary carcinoma cell lines.
AB  - We previously reported that mouse mammary carcinoma cell lines (MMT060562 and
      BALB/c-MC) induced osteoclast formation through production of prostaglandin E2
      (PGE2) in cocultures with mouse bone marrow cells, but the mechanism(s) of PG
      production remained unclear. In the present in vitro and in vivo studies, we
      tested the involvement of cyclo-oxygenase-2 (COX-2), an inducible rate-limiting
      enzyme in PG biosynthesis, in the stimulation of osteoclast formation by mouse
      mammary carcinoma cell lines. Addition of a selective COX-2 inhibitor, JTE-522,
      to cocultures of mammary carcinoma cell lines and bone marrow cells lowered PGE2
      concentration in the culture media and inhibited osteoclast formation in a dose
      dependent manner. Northern blotting showed a very high level of COX-2 messenger
      RNA (mRNA) expression in MMT060562. The mRNA expression was low in BALB/c-MC, but
      it increased when BALB/c-MC and bone marrow cells were cocultured. The results of
      immunocytochemistry for COX-2 protein in respective cultures were compatible with
      the results of COX-2 mRNA. In vivo, BALB/c-MC injected into the heart of Balb/c
      mice metastasized to bone and formed osteolytic lesions in their hindlimbs.
      Histological examination revealed that tumor cells had metastasized to the bone
      marrow cavity and destroyed the bone trabeculae. Immunohistochemistry
      demonstrated that bone marrow stromal cells adjacent to tumor cells expressed COX
      2 protein. These findings suggest that COX-2 plays an important role in the
      osteolysis of bone metastasis in vivo as well as in osteoclast formation in
      cocultures used as an in vitro model of metastatic bone disease.

PMID- 12009008
TI  - Increased bone morphogenetic protein-6 expression in mouse long bones after
      estrogen administration.
AB  - High-dose estrogen administration is known to induce new bone formation in mouse
      long bones. To study the role of regulatory proteins in this response, we
      examined associated changes in femoral messenger RNA (mRNA) for candidate
      factors. 17beta-estradiol (E2) 0.5 mg was administered to intact female mice by
      weekly injection, and Northern blot analysis was performed 1, 2, 4, 8, 12, and 16
      days after the first injection. In contrast to other factors, an increase was
      observed in mRNA for bone morphogenetic protein-6 (BMP-6), which reached
      significance at day 8 and subsequent time-points. Estrogen-induced changes in BMP
      6 protein expression were assessed by immunocytochemistry in longitudinal femoral
      sections. In untreated animals, BMP-6 was expressed by a significant proportion
      of growth plate chondrocytes and a subpopulation of bone marrow cells. In
      contrast, osteoblasts were consistently BMP-6 negative. From as early as 4 days
      after starting estrogen, clusters of slightly elongated BMP-6-positive cells were
      observed within the marrow cavity; the majority were close to active bone
      formation surfaces. Double immunolabeling studies revealed that only
      approximately 10% of BMP-6-positive bone marrow cells co-expressed the osteoblast
      transcription factor Cbfa1 suggesting that they are largely distinct from the
      osteoblast precursor population generated concurrently. BMP-6-positive cells
      expressed neither leukocyte nor erythroid markers (CD45 and TER-119,
      respectively), consistent with a stromal origin. We conclude that estrogen
      induced osteogenesis in female mice is associated with increased levels of BMP-6
      mRNA in mouse femurs, which seems to reflect the emergence of clusters of BMP-6
      positive stromal cells adjacent to active bone formation surfaces. These findings
      raise the possibility that BMP-6 serves as a paracrine mediator of estrogen's
      osteogenic action in mice.

PMID- 12009009
TI  - Cell proliferation and apoptosis during fracture healing.
AB  - This study investigated the relation between cell proliferation and apoptosis
      during fracture healing in a mouse femoral fracture model. Left femoral
      osteotomies were performed in 30 mature male CFLP mice immobilized with uniplanar
      external fixators. Six animals were killed on days 2, 4, 8, 16, and 24
      postfracture for examination. Localization of cell proliferation was examined
      using immunohistochemistry with proliferating cell nuclear antigen (PCNA)
      monoclonal antibody. Apoptotic cells were visualized with the terminal
      deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)
      biotin nick end-labeling (TUNEL) method. Images of each time-specific specimen
      were captured. The total callus area, the positively labeled cells by PCNA, and
      TUNEL per high-power field were quantified. Cell proliferation and apoptosis were
      found coexisting during the entire period of study. In the early phases of
      fracture healing (days 2-8), PCNA-positive labeling was predominant and peaked at
      day 8 and the TUNEL-positive labeling was minimal. In later stages of fracture
      healing (days 16-24), PCNA expression declined at day 16 as callus ossification
      and remodeling spread within the fracture site and apoptosis was the dominant
      cell activity with the TUNEL-positive labeling peaking at day 16 and declining
      sharply at day 24. These cell activities were reflected by the change of fracture
      callus, where there was a continuous increase in total callus area to day 16 and
      subsequent decrease at day 24. This study indicated that cell proliferation and
      apoptosis are coupled events during fracture repair, cell proliferation is active
      at the early stages, and apoptosis is active during the phase of callus
      remodeling.

PMID- 12009010
TI  - Implant design affects markers of bone resorption and formation in total hip
      replacement.
AB  - Concentrations of the bone resorption markers pyridinoline and deoxypyridinoline
      and the bone formation marker osteocalcin were measured in 24-h urine collections
      from 30 subjects who underwent unilateral total hip replacements for
      monoarticular symptomatic osteoarthrosis and 10 controls. The patient groups were
      divided based on the femoral implant type (cemented cobalt alloy stem, cementless
      porous coated cobalt alloy stem, and cementless porous coated titanium alloy
      stem). Urine collections were performed before surgery and then at 3, 6, 12, 24,
      and 36 months. There were significant changes over time in the three patient
      groups for pyridinoline, deoxypyridinoline, and the ratio of osteocalcin to
      deoxypyridinoline (p < or = 0.01), but the control group values did not change
      over time. The resorption markers tended to peak at 3 months and the osteocalcin
      to deoxypyridinoline ratio was more variable, having depressed values in the
      cementless cobalt alloy group and elevated values in the other two groups
      compared with baseline. The cementless cobalt alloy group had higher resorption
      marker levels than the cemented cobalt alloy group at 6, 12, 24, and 36 months
      and higher levels than the cementless titanium alloy group at all postoperative
      times (p < 0.05). The osteocalcin to deoxypyridinoline ratio was lower in the
      cementless cobalt alloy group than in the cemented cobalt alloy group at 3, 6,
      and 24 months and the cementless titanium alloy group at 6, 12, and 24 months (p
      < 0.05). For the cemented cobalt chrome group, the baseline-normalized resorption
      marker values at 3 months and 6 months were correlated with the severity of
      radiographically assessed bone loss at 36 months (0.749 < r < 0.840; p < 0.05).
      For the cementless titanium alloy group, baseline-normalized osteocalcin/
      deoxypyridinoline ratios at 3 months and 6 months were related inversely to
      radiographic bone loss at 36 months (0.687 < r < 0.749; p < 0.05). Thus, body
      fluid markers of bone metabolism change after total hip replacement. In addition,
      the changes in the marker concentrations were sensitive to implant design and
      were correlated with subsequent stress-shielding-induced bone loss.

PMID- 12009011
TI  - Anabolic action of parathyroid hormone is skeletal site specific at the tissue
      and cellular levels in mice.
AB  - The cellular and molecular events triggering the anabolic response of the
      skeleton to exogenous parathyroid hormone (PTH) are not well understood. Despite
      the numerous bone mass studies in rats, few data are available for mice.
      Therefore, we treated 10-week-old female intact C57BL/6J mice with human PTH(1
      34) delivered subcutaneously at a dose of 40 microg/kg per day 5 days a week for
      3 weeks and 7 weeks. Bone mineral density (BMD) of total bone, femur, tibia, and
      lumbar vertebrae was measured weekly by PIXImus. Bone turnover was examined by
      histomorphometry, and gene expression of bone formation and resorption markers
      and osteoclastogenesis regulators in the excised femur and tibia was assessed by
      reverse-transcription polymerase chain reaction (RT-PCR) at 3 weeks and 7 weeks.
      The PTH-stimulated increase in BMD was more prominent in the tibia and femur than
      in the lumbar vertebrae, with an anabolic effect detected within 1-2 weeks and
      BMD continuing to increase. The appearance of a detectable PTH-stimulated
      increase in BMD was slower in the lumbar vertebrae where the increase was only
      significant after 7 weeks of treatment. Histomorphometric analysis of the
      proximal tibia at both 3 weeks and 7 weeks indicated significant time-dependent
      increases in trabecular area, trabecular number, trabecular and cortical widths,
      and osteoblast and osteoid perimeters. In the lumbar vertebrae, these stimulatory
      effects of PTH on trabecular area, trabecular number, and cortical width were
      smaller and not detected until 7 weeks. PTH-stimulated increases in bone turnover
      were evident by increased gene expression of osteocalcin (OC), tartrate-resistant
      acid phosphatase (TRAP), and receptor of activator nuclear factor kappaB (NF
      kappaB) ligand (RANKL) in the tibia and femur. No significant difference in gene
      expression was observed between the two long bone sites. In conclusion, PTH
      exerts an anabolic action at the tissue and cellular levels in intact mice and
      the magnitude and temporal pattern of this anabolic action, as assessed by
      densitometry and histomorphometry, are skeletal site specific.

PMID- 12009012
TI  - Risk factors for fractures of the proximal humerus: results from the EPIDOS
      prospective study.
AB  - Fracture of the proximal humerus is one of the most frequent fractures
      attributable to osteoporosis; yet, it has seldom been studied. Two types of
      factors (related to bone fragility and falls) were evaluated to identify risk
      factors for proximal humerus fractures as well as to examine possible
      interactions between them. Subjects were 6901 white women aged > or =75 years and
      all participated in the EPIDOS study of risk factors for osteoporotic fractures
      (France, 1992-1998). The baseline examination included measurements of femoral
      neck bone mineral density (BMD) and calcaneal ultrasound parameters (speed of
      sound [SOS] and broadband ultrasound attenuation [BUA]), a functional clinical
      examination, and completing a questionnaire on health status and lifestyle.
      During a mean of 3.6 (0.8) years of follow-up, 165 women had a humeral fracture.
      Using multivariate Cox regression models, we identified three predictors related
      to bone fragility-low BMD (relative risk [RR] = 1.4; 95% CI, 1.1-1.7), low SOS
      (RR = 1.3; 95% CI, 1.0-1.6), and maternal history of hip fracture (RR = 1.8; 95%
      CI, 1.0-3.0)-and four fall-related predictors-a previous fall (RR = 3.0; 95% CI,
      1.5-6.1), a low level of physical activity (RR = 2.2; 95% CI, 1.1-4.4), impaired
      balance (RR = 1.8; 95% CI, 1.1-2.9), and pain in lower limb extremity (RR = 1.4;
      95% CI, 1.0-2.1). The effect of these fall-related predictors varied according to
      the BMD level; they were significantly associated with proximal humerus fractures
      in women with osteoporosis (BMD T score < -2.5) but not in nonosteoporotic women.
      The incidence of proximal humerus fracture in women with osteoporosis and a low
      fall risk score (5.1 per 1000 woman-years) was only slightly higher than in
      nonosteoporotic women (4.6 per 1000 woman-years) and similar to the incidence in
      women without osteoporosis but a high fall risk score (5.3 per 1000 woman-years).
      On the other hand, the incidence in women who had both types of risk factors was
      more than two times higher (12.1 per 1000 woman-years) than in women with only
      one of the two risk factors. These results suggest that women who have both types
      of risk factors should receive the highest priority for prevention.

PMID- 12009013
TI  - Type I collagen racemization and isomerization and the risk of fracture in
      postmenopausal women: the OFELY prospective study.
AB  - The Asp1211 residue of the 1209AHDGGR1214 sequence of the C-terminal cross
      linking telopeptide of type I collagen (CTX) can undergo spontaneous post
      translational modifications, namely, racemization and isomerization, which result
      in the formation of four isomers: the native form (alpha-L) and three age-related
      forms, that is, an isomerized form (beta-L), a racemized form (alpha-D), and an
      isomerized/racemized (beta-D) form. Previous studies have suggested that changes
      in the pattern of type I collagen racemization/isomerization, which can be
      assessed in vivo by measuring the degradation products of the CTX isoforms, may
      be associated with alterations of bone structure. The aim of this study was to
      examine prospectively the value of the different urinary CTX isoforms and their
      related ratio in the prediction of osteoporotic fractures in 408 healthy
      untreated postmenopausal women aged 50-89 years (mean, 64 years) who were part of
      the OFELY cohort. During a median 6.8 years follow-up, 16 incident vertebral
      fractures and 55 peripheral fractures were recorded in 65 women. The baseline
      levels of the four CTX isoforms in women who subsequently had a fracture were
      compared with those of the 343 women who did not fracture. At baseline, women
      with fractures had increased levels of ratios of native alpha-L-CTX to age
      related isoforms (beta-L, alpha-D, and beta-D) compared with controls (p < 0.01).
      In logistic regression analysis after adjustment for age, prevalent fractures,
      and physical activity, women with levels of alpha-L/beta-L, alpha-L/alpha-D, and
      alpha-L/beta-D-CTX ratios in the highest quartile had a 1.5- to 2-fold increased
      risk of fractures compared with women with levels in the three lowest quartiles
      with relative risk (RR) and 95% CI of 2.0 (1.2-3.5), 1.8 (1.02-2.7), and 1.5 (0.9
      2.7), respectively. Adjustment of alpha-L/beta-L and alpha-L/alpha-D-CTX ratios
      by the level of bone turnover assessed by serum bone alkaline phosphatase (ALP)-
      or femoral neck bone mineral density (BMD) decreased slightly the RR, which
      remained significant for the alpha-L/beta-L-CTX ratio (RR [95%] CI, 1.8 [1.1-3.2]
      after adjustment for bone ALP, 1.8 [1.03-3.1] after adjustment for BMD, and 1.7
      [0.95-2.9] after adjustment for both bone ALP and BMD). Women with both high
      alpha-L/beta-L-CTX ratio and high bone ALP had a 50% higher risk of fracture than
      women with either one of these two risk factors. Similarly, women with both
      increased CTX ratio and low femoral neck BMD (T score < -2.5) had a higher risk
      of fracture with an RR (95% CI) of 4.5 (2.0-10.1). In conclusion, increased
      urinary ratio between native and age-related forms of CTX, reflecting decreased
      degree of type I collagen racemization/isomerization, is associated with
      increased fracture risk independently of BMD and partly of bone turnover rate.
      This suggests that alterations of type I collagen isomerization/racemization that
      can be detected by changes in urinary CTX ratios may be associated with increased
      skeletal fragility.

PMID- 12009014
TI  - Bone mineral response to a 7-month randomized controlled, school-based jumping
      intervention in 121 prepubertal boys: associations with ethnicity and body mass
      index.
AB  - We examined the effects of a 7-month jumping intervention (10 minutes, 3 times
      per week) on bone mineral gain in prepubertal Asian and white boys (10.3+/-0.6
      years, 36.0+/-9.2 kg) at 14 schools randomized to control (n = 60) and
      intervention (n = 61) groups. Intervention and control groups had similar mean
      baseline and change in height, weight, lean mass and fat mass, baseline areal
      bone mineral density (aBMD; g/cm2), bone mineral content (BMC; g; dual-energy X
      ray absorptiometry [DXA], QDR 4500W), and similar average physical activity and
      calcium intakes. Over 7 months, the intervention group gained more total body
      (TB) BMC (1.6%,p < 0.01) and proximal femur (PF) aBMD (1%, p < 0.05) than the
      control group after adjusting for age, baseline weight, change in height, and
      loaded physical activity. We also investigated the 41 Asian and 50 white boys
      (10.2+/-0.6 years and 31.9+/-4.4 kg) who were below the 75th percentile (19.4
      kg/m2) of the cohort mean for baseline body mass index (BMI). Boys in the
      intervention group gained significantly more TB and lumbar spine (LS) BMC, PF
      aBMD, and trochanteric (TR) aBMD (+ approximately2%) than boys in the control
      group (adjusted for baseline weight, final Tanner stage, change in height, and
      loaded physical activity). Bone changes were similar between Asians and whites.
      Finally, we compared the boys in the control group (n = 16) and the boys in the
      intervention group (n = 14) whose baseline BMI fell in the highest quartile
      (10.5+/-0.6 years and 49.1+/-8.2 kg). Seven-month bone changes (adjusted as
      aforementioned) were similar in the control and intervention groups. In summary,
      jumping exercise augmented bone mineral accrual at several regions equally in
      prepubertal Asian and white boys of average or low BMI, and intervention effects
      on bone mineral were undetectable in high BMI prepubertal boys.

PMID- 12009015
TI  - Osteocyte-specific monoclonal antibody MAb OB7.3 is directed against Phex
      protein.
AB  - Osteocytes are the most abundant cells in bone; however, relatively little is
      known about their properties and functions. The development of monoclonal
      antibody MAb OB7.3 directed against chicken osteocytes enabled us to purify
      osteocytes from enzymatically isolated bone cells. Cultures of purified
      osteocytes were used to gain better insight into the role of osteocytes in bone
      metabolism. Until now, the antigen of MAb OB7.3 has not been elucidated. In this
      study, we examined the antigen to which this osteocyte-specific antibody is
      directed. Immunoprecipitation and purification of the protein, followed by amino
      acid sequence analysis of two isolated peptides, revealed that the antigen has
      high homology to human and murine PHEX/Phex protein sequences (PHosphate
      regulating gene with homology to Endopeptidases on the X chromosome). The OB7.3
      antigen was therefore identified as chicken Phex protein. In addition, using
      suppression subtractive hybridization, we obtained a complementary DNA (cDNA)
      sequence of 502 base pairs (bp) with high homology to the human and murine
      PHEX/Phex genes. This method was applied to identify genes, which are
      differentially expressed in osteocytes compared with osteoblasts. The results
      also suggest that Phex is expressed at higher levels in chicken osteocytes
      compared with osteoblasts. Reverse-transcription polymerase chain reaction (RT
      PCR) and Northern blot analyses supported these findings. The function of Phex is
      not completely understood. However, it is known that the gene is preferentially
      expressed in bone and that mutations in PHEX/Phex lead to X-linked
      hypophosphatemia and bone mineralization abnormalities. Our findings suggest that
      osteocytes play an important role in the Phex-regulated phosphate handling in the
      kidney and in bone.

PMID- 12009016
TI  - Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F
      fluoride positron emission tomography.
AB  - The purpose of this study was to quantify indices of regional bone metabolism in
      Paget's disease and to compare these indices with normal bone using dynamic 18F
      fluoride positron emission tomography (PET). Seven patients with vertebral
      Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans
      included a diseased vertebra and an adjacent normal vertebra. Arterial plasma
      input functions were also measured. A three-compartment, four-parameter model was
      used with nonlinear regression analysis to estimate bone kinetic variables.
      Compared with normal bone, pagetic bone demonstrated higher values of plasma
      clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per
      milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs.
      1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased
      mineralization and blood flow, respectively. Release of 18F-fluoride from bone
      mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of
      18F-fluoride to bone mineral. The notional volume of the extravascular bone
      compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the
      unidirectional extraction efficiency from the extravascular space to bone mineral
      (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p =
      0.028), describing the rate of transfer from the bone extravascular compartment
      to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic
      marrow space of pagetic bone may be less accessible for return to plasma. These
      findings confirm some of the known pathophysiology of Paget's disease, introduce
      some new observations, and show how dynamic 18F-fluoride PET may be of value in
      the measurement of regional metabolic parameters in focal bone disorders.

PMID- 12009017
TI  - Differential activation of cysteine-substitution mutants of fibroblast growth
      factor receptor 3 is determined by cysteine localization.
AB  - Various human skeletal disorders are thought to be caused by mutations in
      fibroblast growth factor receptor 3 (FGFR3). These result in chronic FGFR3
      hyperactivation and inhibition of bone growth. One such disorder, thanatophoric
      dysplasia, the most common form of sporadic, lethal dwarfism, is associated
      frequently with cysteine substitutions (G370C, S371C, and Y373C) in the
      extracellular juxtamembrane region of the receptor. These mutations have been
      suggested to induce disulfide-mediated receptor dimerization and constitutive
      activation. An adjacent cysteine substitution (G375C) leads to a less severe form
      of human dwarfism, achondroplasia, suggesting that the intensity of FGFR3
      activation by these cross-links may be position dependent. To test this
      hypothesis, we have sequentially replaced each amino acid at positions 370-375 of
      FGFR3 with cysteine. Expression of each of these mutant forms in 293T cells led
      to their spontaneous, ligand-independent dimerization and increased basal
      phosphorylation. Wild-type (WT) FGFR3 became dimerized and phosphorylated only on
      FGF stimulation. Among the mutants, only two (G370C and S371C) caused high basal
      phosphorylation with significantly increased constitutive levels of mitogen
      activated protein kinase (MAPK) phosphorylation and c-fos transcription. This
      activity was probably caused by mutant homodimer pairs, because WT-mutant
      heterodimers were observed only in the presence, but not in the absence, of FGF1.
      The high spontaneous activity of the mutants in positions 370-371, unlike those
      in 372-375, affirms their known involvement with thanatophoric dysplasia. We
      conclude that the G370C and S371C mutant receptors spontaneously dimerize in the
      correct spatial orientation required for effective signal transduction, whereas
      the 372-5 mutants, like the WT receptor, may achieve this orientation only on
      ligand binding.

PMID- 12009018
TI  - Prostaglandin E2 induces interaction between hSlo potassium channel and Syk
      tyrosine kinase in osteosarcoma cells.
AB  - Prostaglandins (PGs) are important mediators of bone response to growth factors,
      hormones, inflammation, or mechanical strains. In this study, we show that in
      MG63 osteosarcoma cells, prostaglandin E2 (PGE2) produces the opening of a large
      conductance Ca2+-dependent K+ channel (BK). This PGE2-mediated channel opening
      induces the recruitment of various tyrosine-phosphorylated proteins on the hSlo
      alpha-subunit of BK. Because the C-terminal domain of hSlo encompasses an
      immunoreceptor tyrosine-based activation motif (ITAM), we show that the Syk
      nonreceptor tyrosine kinase, reported yet to be expressed mainly in hematopoietic
      cells, is expressed also in osteoblastic cells, and recruited on this ITAM after
      a PGE2-induced docking/activation process. We show that Syk/hSlo association is
      dependent of an upstream Src-related tyrosine kinase activity, in accord with the
      classical two-step model described for immune receptors. Finally, we provide
      evidence that this Syk/hSlo interaction does not affect the electrical features
      of BK channels in osteosarcoma cells. With these data, we would like to suggest
      the new notion that besides its conductance function, hSlo channel can behave in
      bone cells, as a true transduction protein intervening in the bone remodeling
      induced by PGE2.

PMID- 12009019
TI  - Vitamin D analogue-specific recruitment of vitamin D receptor coactivators.
AB  - Synthetic ligands for the vitamin D receptor (VDR) are potential therapeutic
      agents for metabolic, neoplastic, and autoimmune disorders. Some of these ligands
      have similar or more potent antiproliferative, yet reduced hypercalcemic actions,
      than calcitriol. However, the mechanisms for these differential actions have not
      been clearly defined. We hypothesized that these gene- and tissue-specific
      effects may relate to ligand-directed selective recruitment of transcriptional
      coactivators. To identify key elements in ligand structure that facilitate VDR
      coactivator interactions, the current studies assessed the ability of the VDR to
      recruit the coactivators GRIP1 and RAC3 following activation by a series of 20-R-
      and 20-S (20-epi)-modified analogues. The strength of VDR-coactivator
      interactions was ligand-specific and did not always correlate with ligand
      receptor binding affinity. In general, the 20-epi analogues enhanced these
      interactions, whereas the 20-R-modified analogues were less effective than
      calcitriol. The 16-ene,23-yne modification and fluorinated substituents to the
      side-chain attenuated interaction with coactivators. The enhanced ability of the
      VDR to recruit GRIP1 following activation by the 20-epi analogues was consistent
      with potentiation of 20-epi analogue-induced transactivation of the osteocalcin
      gene promoter by GRIP1. Overall, the structure of the ligand side-chain as well
      as its orientation seemed to affect the avidity of coactivator binding. These
      results suggest that selective recruitment of coactivators may contribute to gene
      and tissue-specific effects of vitamin D analogues.

PMID- 12009020
TI  - Neuromuscular and psychomotor function in elderly subjects who fall and the
      relationship with vitamin D status.
AB  - Vitamin D and calcium supplementation significantly reduces the incidence of
      fractures. Evidence suggests vitamin D deficiency impairs neuromuscular function,
      causing an increase in falls and thereby fractures. The relationship between
      vitamin D, functional performance, and psychomotor function in elderly people who
      fall was examined in a prospective cross-sectional study. Patients were recruited
      from a falls clinic and stratified according to serum 25-hydroxyvitamin-D levels
      (25OHD): group 1, 25OHD < 12 microg/liter; group 2 25OHD, 12-17 microg/liter; and
      group 3, 25OHD > 17 microg/liter. Healthy elderly volunteers with 25OHD > 17
      microg/liter comprised group 4 (n = 20/group). Measures included aggregate
      functional performance time (AFPT, seconds), isometric quadriceps strength
      (Newtons), postural sway (degrees), and choice reaction time (CRT, seconds).
      Serum bone biochemistry, 25OHD, and parathyroid hormone levels were measured.
      Patients who fell had significantly impaired functional performance, psychomotor
      function, and quadriceps strength compared with healthy subjects (AFPT: 51.0 s
      vs. 32.8 s,p < 0.05; CRT: 1.66 s vs. 0.98 s,p < 0.05; strength: 223N vs. 271N, t
      = 2.35, p = 0.02). Group 1 had significantly slower AFPT (66.0 s vs. 44.8 s, t =
      4.15, p < 0.05) and CRT (2.37 s vs. 0.98 s, t = 3.59, p < 0.05) than groups 2 and
      3. Group 1 had the greatest degree of postural sway and the weakest quadriceps
      strength, although this did not reach significance. Multivariate analysis
      revealed 25OHD as an independent variable for AFPT, CRT, and postural sway. PTH
      was an independent variable for muscle strength. Older people who fall have
      impaired functional performance, psychomotor function, and muscle strength.
      Within this group, those with 25OHD < 12 microg/liter are the most significantly
      affected.

PMID- 12009021
TI  - Bone morphogenetic protein signals are required for cartilage formation and
      differently regulate joint development during skeletogenesis.
AB  - The bone morphogenetic protein (BMP) family consists of a large number of members
      and has diverse biological activities during development. Various tissues express
      pleural BMP family members, which seem to cooperatively regulate developmental
      events. Here, multiple BMP signals were inactivated in chondrocytes to clarify
      the function of BMPs during skeletogenesis. To obtain tissue-specific
      inactivation, Noggin gene (Nog) was overexpressed in cartilage under the control
      of a2(XI) collagen gene (Collla2) promoter/enhancer sequences. The resultant
      transgenic mice lacked most of their cartilaginous components, suggesting that
      cartilage does not develop without BMP signals. These effects seem to be mediated
      through down-regulation of Sox9 expression. Conversely, specific BMP signals were
      activated in the skeleton by targeted expression of Bmp4 in cartilage and the
      resultant phenotype was compared with that of transgenic mice expressing growth
      and differentiation factor-5 (GDF-5), another BMP family member. Overactivity of
      Bmp4 in the skeleton caused an increase of cartilage production and enhanced
      chondrocyte differentiation, as GDF5 expression did, but it did not disturb joint
      formation as GDF5 did. During skeletogenesis, unique roles of each BMP may reside
      in the regulation of joint development. Together with the common effect on the
      cartilage overproduction by Bmp4 and GDF5 overactivation, loss of cartilage by
      inactivation of multiple BMPs in Noggin transgenic mice indicates that signals
      for cartilage production are reinforced by multiple BMPs exclusively. These
      conclusions may account for the reason why multiple BMPs are coexpressed in
      cartilage.

PMID- 12009022
TI  - Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue:
      complementary roles in bone remodeling regulation?
AB  - Osteocyte apoptosis appears to play a key role in the mechanism by which
      osteoclastic resorption activity targets bone for removal, because osteocyte
      apoptosis occurs in highly specific association with microdamage and subsequent
      remodeling after fatigue. However, beyond terminal deoxynucleotidyl transferase
      (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL)
      assay, little is known about the mechanisms controlling osteocyte apoptosis in
      vivo. In the current studies, expression of Bax, a proapoptotic gene product, and
      Bcl-2, an antiapoptotic gene product, was determined in osteocytes of fatigued
      rat bone using immunocytochemical staining and compared with TUNEL staining
      patterns. Bax and Bcl-2 were evident in osteocytes by 6 h after loading.
      Moreover, Bax and Bcl-2 in osteocytes were expressed differently as a function of
      distance from microdamage sites. The peak of Bax expression and TUNEL+ staining
      in osteocytes was observed immediately at the microcrack locus, which is where
      bone resorption occurs in this system; in contrast, Bcl-2 expression, the
      antiapoptotic signal, reached its greatest level at some distance (1-2 mm) from
      microcracks. These data suggest that near sites of microinjury in bone, those
      osteocytes that do not undergo apoptosis are prevented from doing so by active
      protection mechanisms. Moreover, the zone of apoptotic osteocytes around
      microcracks was effectively "walled in" by a surrounding halo of surviving
      osteocytes actively expressing Bc1-2. Thus, the expression pattern of apoptosis
      inhibiting gene products by osteocytes surrounding the apoptotic osteocyte at
      microdamage sites also may provide important signals in the guidance of
      resorption processes that occur in association with osteocyte apoptosis after
      fatigue.

PMID- 12009023
TI  - Use of a phage display technique to identify potential osteoblast binding sites
      within osteoclast lacunae.
AB  - There is a temporal coupling between the processes of bone resorption and bone
      formation in normal skeletal remodeling. That is, osteoblastic activity usually
      follows episodes of osteoclastic activity. However, what has not been universally
      appreciated is that there also is a spatial coupling between these processes.
      Bone formation only occurs in the immediate vicinity of the resorptive event. In
      this study, we describe a phage display technique that has been used to identify
      the mechanisms by which osteoblasts recognize components of the prior resorbed
      lacunar surface. Using a type V tartrate-resistant acid phosphatase (TRAP) as the
      bait and a random peptide M13 phage display library as the probe, we have
      identified specific sequences that show a very high affinity for TRAP. One of
      these peptides, designated clone 5, has a subnanomolar Kd for TRAP, interacts
      with TRAP in a Far-Western assay, binds exclusively to TRAP within osteoclast
      lacunae, is present in osteoblasts, and can effectively block osteoblast binding
      to resorption surfaces. The clone 5 peptide shows a high homology to glypican 4
      (GPC4), a proteoglycan attachment receptor found in a number of cell types.

PMID- 12009024
TI  - Prodrug and antedrug: two diametrical approaches in designing safer drugs.
AB  - The prodrug and antedrug concepts, which were developed to overcome the physical
      and pharmacological shortcomings of various therapeutic classes of agents, employ
      diametrically different metabolic transformations. The prodrug undergoes a
      predictable metabolic activation prior to exhibiting its pharmacological effects
      in a target tissue while the antedrug undergoes metabolic deactivation in the
      systemic circulation upon leaving a target tissue. An increased therapeutic index
      is the aspiration for both approaches in designing as well as evaluation
      criteria. The recent research endeavors of prodrugs include the gene-directed and
      antibody-directed enzymatic activation of a molecule in a targeted tissue, organ
      specific delivery, improved bioavailabilities of nucleosides and cellular
      penetration of nucleotides. As for antedrugs, emphasis in research has been based
      upon the design and synthesis of systemically inactive molecule by incorporating
      a metabolically labile functional group into an active molecule.

PMID- 12009025
TI  - Synthesis and SAR studies for the inhibition of TNF-alpha production. Part 2. 2
      [3-(Cyclopentyloxy)-4-methoxyphenyl]-substituted-1-isoindolinone derivatives.
AB  - This study describes the synthesis and in vitro evaluation of 2-[3
      (cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone derivatives substituted on
      benzene moiety of isoindoline ring for the inhibition of TNF-alpha production.
      From this study, we have found the 6-C position on isoindolinone ring is an
      optimal derivatization site. Among the compounds synthesized, 6-amino-2-[3
      (cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (6) was the most potent in
      inhibitory activity of TNF-alpha production in LPS-stimulated RAW264.7 cells.

PMID- 12009026
TI  - DNA dynamics: a fluorescence resonance energy transfer study using a long
      lifetime metal-ligand complex.
AB  - Fluorescent probes bound to DNA typically display nanosecond decay times and
      reveal only nanosecond motions. We extend the time range of measurable DNA
      dynamics using [Ru(bpy)2(dppz)]2+ (bpy=2,2'-bipyridine, dppz=dipyrido[3,2-a:2',3'
      c]phenazine) (RuBD) which displays a mean lifetime near 90 ns. To test the
      usefulness of RuBD as a probe for diffusive processes in calf thymus DNA, we
      compared the efficiencies of fluorescence resonance energy transfer (FRET) using
      three donors which display lifetimes near 5 ns for acridine orange (AO), 22 ns
      for ethidium bromide (EB) and 92 ns for RuBD, with nile blue (NB) as the
      acceptor. The Forster distances for AO-NB, EB-NB and RuBD-NB donor-acceptor pairs
      were 42.3, 52.3, and 30.6 A, respectively. All three donors showed dramatic
      decreases in fluorescence intensities and more rapid intensity decays with
      increasing NB concentrations. The intensity decays of AO and EB in the presence
      of varying concentrations of NB were satisfactorily described by the one
      dimensional FRET model without diffusion (Blumen and Manz, 1979). In the case of
      the long-lifetime donor RuBD, the experimental phase and modulation somewhat
      deviated from the recovered values computed from this model. The recovered NB
      concentrations and FRET efficiencies from the model were slightly larger than the
      expected values, however, the recovered and expected values did not show a
      significant difference. Thus, it is suggested that the lifetime of RuBD is too
      short to measure diffusive processes in calf thymus DNA.

PMID- 12009027
TI  - Pseudoguaianolides isolated from Inula britannica var. chinenis as inhibitory
      constituents against inducible nitric oxide synthase.
AB  - Three pseudoguaianolide type sesquiterpenes, bigelovin (1), 2,3-dihydroaromaticin
      (2), and ergolide (3) were isolated as inhibitory constituents against inducible
      nitric oxide synthase (iNOS) from the flowers of Inula britannica var. chinensis.
      Bigelovin (1) exhibited a highly potent inhibitory activity on lipopolysaccharide
      (LPS)-induced iNOS in murine macrophage RAW 264.7 cells with an IC50 value of
      0.46 mM, which is about 8 times more potent than the known selective inhibitor of
      iNOS, L-N6-(1-iminoethyl)lysine (IC50 3.49 microM). 2,3-Dihydroaromaticin (2) and
      ergolide (3) also exhibited potent inhibitory activities on LPS-induced iNOS with
      IC50 values of 1.05 and 0.69 microM, respectively.

PMID- 12009028
TI  - Antimicrobial constituents of Foeniculum vulgare.
AB  - A phenyl propanoid derivative, dillapional(1) was found to be a antimicrobial
      principle of the stems of Foeniculum vulgare (Umbelliferae) with MIC values of
      125, 250 and 125/ against Bacillus subtilis, Aspergillus niger and Cladosporium
      cladosporioides, respectively. A coumarin derivative, scopoletin(2) was also
      isolated as marginally antimicrobial agent along with inactive compounds,
      dillapiol(3), bergapten(4), imperatorin(5) and psolaren(6) from this plant. The
      isolates 1-6 were not active against the Escherichia coli.

PMID- 12009029
TI  - Immunomodulatory activity of protein-bound polysaccharide extracted from
      Chelidonium majus.
AB  - In the course of searching immunomodulators from natural sources, the protein
      bound polysaccharide, CM-Ala, has been isolated from the water extract of
      Chelidonium majus L. (Papaveraceae). The immunostimulatory characteristics have
      been investigated in several experiments such as generation of activated killer
      (AK) cells, proliferation of splenocytes, activation of macrophages and
      granulocyte macrophage-colony forming cell (GM-CFC) assay. Of the fractions
      obtained using Sephacryl S200 column chromatography, CM-Ala was the most
      effective fraction that augmented the cytotoxicity against Yac-1 tumor cells from
      0.88% to 34.18% by culturing with splenocytes for 5 days. CM-Ala also enhanced
      nitric oxide production by two fold in peritoneal macrophages and exhibited
      antitumor activity. It showed mitogenic activity on both spleen cells and bone
      marrow cells. CM-Ala induced proliferation of splenocytes by 84 fold and
      increased GM-CFC numbers by 1.48 fold over than the non-treated. On the contrary,
      CM-Ala had cytotoxic activity to a diverse group of tumor cells. From the above
      results, we proposed that CM-Ala has a possibility of an effective antitumor
      immunostimulator.

PMID- 12009030
TI  - Fecal metabolic activities of herbal components to bioactive compounds.
AB  - The herbal components should be transformed to bioactive compounds by the
      intestinal bacteria and then expressed the pharmacological action of herbal
      medicines. Human fecal enzyme activities related to the metabolism of herbal
      components were measured. The metabolic activities of puerarin, poncirin,
      glycyrrhizin, ginsenoside Rb1 and ginsenoside Rb2 to their bioactive compounds
      were 3.5 +/- 1.18, 333.1 +/-183.64, 95.7 +/- 107.1, 28.6 +/- 10.32 and 20.8 +/-
      13.3 micromol/ h/g, respectively. The profile of these metabolic activities of
      glycyrrhizin and ginsenosides were not changed even if herbal extracts, water
      extract of Glycyrrhizae Radix and Ginseng Radix, instead of the isolated
      compounds were used. All the enzyme activities tested were not different between
      male and female, and between ages. However, the difference of these enzyme
      activities in individuals was significant. These results suggest that the
      metabolic activity of herbal components to bioactive compounds may be a factor of
      constitutional classification, and could be available for constitutional
      classifications, if the constitutional herbal medicines were used.

PMID- 12009031
TI  - The effect of linarin on LPS-induced cytokine production and nitric oxide
      inhibition in murine macrophages cell line RAW264.7.
AB  - The herb, Chrysanthemum zawadskii var, latilobum commomly known as Gu-Jul-Cho in
      Korea, used in traditional medicine to treat pneumonia, bronchitis, cough, common
      cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and
      hypertension. Linarin is the main active compound and the biological mechanisms
      of its activity are unclear. It is believed that effects of this herb may be
      exerted through the pluripotent effectors of linarin due to its ability to treat
      a variety of afflictions. In this study, the effects of linarin on the mouse
      macrophages cell line, RAW 264.7, were investigated. It was found that linarin
      could activate macrophages by producing cytokines. Monocytes and tissue
      macrophages produce at least two groups of protein mediators of inflammation,
      interleukin 1 (IL-1) and the tumor necrosis factor (TNF). Recent studies have
      shown that TNF and IL-1 modulate the inflammatory function of endothelial cells,
      leukocytes, and fibroblasts. TNF-alpha production by macrophages treated with
      linarin occured in a dose dependent manner. However, IL-1 production was largely
      unaffected by this natural product. This study demonstrated the ability of
      linarin to activate macrophages both directly and indirectly. Linarin also affect
      both cytokine production and nitric oxide inhibition, in addition to the
      expression of some surface molecules. Nitric oxide (NO), derived from L-argin
      ine, is produced by two forms(constitutive and inducible) of nitric oxide
      synthase (NOS). The NO produced in large amounts by inducible NOS is known to be
      responsible for the vasodilation and hypotension observed in septic shock.
      Linarin was found to inhibit NO production in the LPS-activated RAW 264.7 cells.
      Linarin may be a useful candidate as a new drug for treating endotoxemia and the
      inflammation accompanied by NO overproduction. The linarin-treated total
      lymphocytes exhibited cytotoxicity in a dose dependent manner between 20
      microg/ml and 40 microg/ml. These results suggest that linarin may function
      through macrophage activation.

PMID- 12009032
TI  - Effects of high molecular weight water-soluble chitosan on in vitro fertilization
      and ovulation in mice fed a high-fat diet.
AB  - A high molecular weight water-soluble chitosan (WSC) with an average molecular
      weight of 300 kD and a deacethylation level of over 90% was produced using a
      simple multi-step membrane separation process. It is known that WSC prevents
      obesity induced by a high-fat diet. Consequently, this study investigated whether
      or not WSC improved the ovarian dysfunction caused by obesity in mice. The mice
      were fed a high density protein and lipid diet for 4 weeks, followed by the
      administration of WSC at 480 mg/kg body weight per day for 4 days. Thereafter,
      the changes in body weight, ovulation rate, in vivo and in vitro fertilization
      and embryonic development were measured. WSC markedly reduced the body weight of
      obese mice fed with a high-fat diet, but not in mice fed with a normal diet. WSC
      had significant effects on the ovulation rate, both the in vivo and in vitro
      fertilization rates and embryonic development. These results indicate an
      improvement in the ovarian and oviduct dysfunction caused by obesity, and suggest
      an adjustment in the internal secretions and metabolic functions.

PMID- 12009033
TI  - Combination of vitamin C and rutin on neuropathy and lung damage of diabetes
      mellitus rats.
AB  - We investigated the role of vitamin C or rutin on neuropathy and lung damage of
      diabetic mellitus (DM) rats. Norepinephrine content was significantly decreased
      in sciatic nerves'of DM rats compared with non-DM controls but vitamin C had no
      effect on decreases of norepinephrine. 2,4-dinitrophenylhydrazine (DNPH)
      incorporation, which is biomarker of protein oxidation, was increased in sciatic
      nerve of DM rats as compared with normal control. However, vitamin C had no
      effects on increases of DNPH incorporation. We measured the content of conjugated
      dienes (CD) as a biomarker of lipid oxidation in sciatic nerve. CD was increased
      in DM as compared with normal control. Vitamin C or rutin had no effects on
      increases of CD. However, Rutin plus vitamin C significantly decreased the
      content of CD as compared with DM rats. In lung of DM rats, DNPH incorporation or
      CD was increased as compared with normal control. Vitamin C or Rutin had no
      effects on increases of CD. However, Rutin plus vitamin C significantly decreased
      the content of DNPH incorporation or CD in lung tissue. Vitamin C caused marked
      pathological changes such as the increases of parenchyma and the thickening of
      alveolar septa in the lung of DM. Rutin had protective effects on the
      pathological changes in the lung of DM rats. In conclusion, Vitamin C had no
      effects on oxidative parameter, such as DNPH incorporation or CD, and on the
      decreases of norepinephrine content in DM rats. Vitamin C caused the marked
      pathological changes in the lung of DM rats but rutin had protective effects
      against the pathological changes.

PMID- 12009034
TI  - Cortex mori extract induces cancer cell apoptosis through inhibition of
      microtubule assembly.
AB  - The water extract from the root bark of Cortex Mori (CM, Morus alba L.:
      Sangbaikpi), a mulberry tree, has been known in Chinese traditional medicine to
      have antiphlogistic, diuretic, and expectorant properties. In this study, the
      cytotoxicity of CM against tumor cells and its mechanism was examined. CM
      exhibited cytotoxic activity on K-562, B380 human leukemia cells and B16 mouse
      melanoma cells at concentrations of > 1 mg/ml. A DNA fragmentation, PARP
      cleavage, and nuclear condensation assay showed that those cells exposed to CM
      underwent apoptosis. The water extract of Scutellarie Radix (SR) was used as a
      negative control and showed no cytotoxicity in those cells. The flow cytometric
      profiles of the CM-treated cells were also indicative of apoptosis. However, they
      did not appear to exert the G1 arrest, which is observed in other tubulin
      inhibitor agents such as vincristine, taxol. The protein-binding test using
      Biacore and a microtubule assembly-disassembly assay provided evidence showing
      that CM bound to the tubulins resulting in a marked inhibition of the assembly,
      but not the disassembly of microtubules. The possible nonspecific effect of the
      CM extract could be excluded due to the results using SR, which did not affect
      the assembly process. Overall, the water extract of CM induces apoptosis of tumor
      cells by inhibiting microtubule assembly.

PMID- 12009035
TI  - Induction of cytochrome P450 1A and 2B by alpha- and beta-ionone in Sprague
      Dawley rats.
AB  - Beta-lonone has been reported to induce the cytochrome P450 (P450) 281 in rats.
      In this study, the effects of beta-ionone and an isomer, alpha-ionone, on liver
      P450 1A and 2B expression in Sprague Dawley rats were investigated. Subcutaneous
      administration of alpha- and beta-ionone 72 and 48 hr prior to sacrificing the
      animals induced the liver microsomal P450 1A and 2B proteins. P450 2B1 induction
      was associated with the accumulation of its corresponding mRNA. Induction by beta
      ionone was much higher than that by a-ionone in both the mRNA and protein levels.
      When the route of administration was compared, P450 2B was induced more strongly
      after oral administration compared to that after subcutaneous injection. A single
      oral dose of 100, 300 and 600 mg/kg of alpha- and beta-ionone for 24 h induced
      P450 2B1-selective pentoxyresorufin O-depentylase activity comparably in a dose
      dependent manner. In addition, alpha- and beta-ionone induced the P450 1A and 2B
      proteins. These results suggest that alpha- and beta-ionone might be potent P450
      281 inducers in rats, and that both ionones may be useful for examining the role
      of metabolic activation in chemical-induced toxicity where metabolic activation
      is required.

PMID- 12009036
TI  - Inhibition of THIP on morphine-induced hyperactivity, reverse tolerance and
      postsynaptic dopamine receptor supersensitivity.
AB  - This study was performed to investigate the effect of tetrahydroisoxazolopyridine
      (THIP), a GABAA agonist, on the morphine-induced hyperactivity, reverse tolerance
      and postsynaptic dopamine receptor supersensitivity in mice. A single
      administration of morphine induced hyperactivity in mice. However, the morphine
      induced hyperactivity was inhibited dose-dependently by the administration of
      THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of
      morphine resulted in a reverse tolerance to the hyperactivity caused by morphine
      (10 mg/kg, s.c.). THIP inhibited the development of reverse tolerance in the mice
      that had received the repeated same morphine (10 mg/kg, s.c.) doses. The
      postsynaptic dopamine receptor super-sensitivity, which was evidenced by the
      enhanced ambulatory activity after the administration of apomorphine (2 mg/kg,
      s.c.), also developed in the reverse tolerant mice. THIP also inhibited the
      development of the postsynaptic dopamine receptor supersensitivity induced by the
      chronic morphine administration. These results suggest that the hyperactivity,
      reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by
      morphine can be inhibited activating the GABAA receptors.

PMID- 12009037
TI  - Transcriptional regulation of the glial cell-specific JC virus by p53.
AB  - The human polyomavirus JC virus is the etiologic agent of progressive multifocal
      leukoencephalopathy (PML). As the JC virus early promoter directs cell-specific
      expression of the viral replication factor large T antigen, transcriptional
      regulation constitutes a major mechanism of glial tropism in PML. It has been
      demonstrated that SV40 or JC virus large T antigen interacts with p53 protein and
      regulates many viral and cellular genes. In this study we found that p53
      represses the JC virus early promoter in both glial and nonglial cells. To
      identify the cis-regulatory elements responsible for p53-mediated repression,
      deletional and site-directed mutational analyses were performed. Deletion of the
      enhancer region diminished p53-mediated transcriptional repression. However,
      point mutations of several transcription factor binding sites in the basal
      promoter region did not produce any significant changes. In support of this
      observation, when the enhancer was fused to a heterologous promoter, p53 reduced
      the promoter activity about three fold. These results indicate that the enhancer
      region is important for the repression of JC virus transcription by p53.
      Furthermore, coexpression of JC virus T antigen with a p53 protein abolished p53
      mediated repression of the JC virus early promoter in non-glial cells, but not in
      glial cells. This finding suggests that T antigen interacts with p53 and
      regulates JC virus transcription in a cell-specific manner.

PMID- 12009038
TI  - Child-care structure-->process-->outcome: direct and indirect effects of child
      care quality on young children's development.
AB  - With datafrom the NICHD Study of Early Child Care, we used structural equation
      modeling to test paths from structural indicators of child-care quality,
      specifically caregiver training and child-staff ratio, through a process
      indicator to child outcomes. There were three main findings: (a) Quality of
      maternal caregiving was the strongest predictor of cognitive competence, as well
      as caregivers' ratings of social competence; (b) quality of nonmaternal
      caregiving was associated with cognitive competence and caregivers' ratings of
      social competence; and (c) there was a mediated path from both caregiver training
      and child-staff ratio through quality of nonmaternal caregiving to cognitive
      competence, as well as to caregivers' ratings of social competence, that was not
      accounted for entirely by family variables. These findings provide empirical
      support for policies that improve state regulations for caregiver training and
      child-staff ratios.

PMID- 12009039
TI  - Speakers' overestimation of their effectiveness.
AB  - Successful communication depends in part on an ability to anticipate
      miscommunication. We investigated speakers' ability to gauge their addressees'
      understanding. Participants in our experiments were asked to say ambiguous
      sentences while attempting to convey a specific intention to their addressee.
      When they estimated the addressee's understanding of the intended meaning, they
      showed a consistent tendency to overestimate their effectiveness. They expected
      the addressee to understand more often than the addressee actually did. In
      contrast, overhearers who were informed about the speakers intention did not
      systematically overestimate the speakers' effectiveness. Our findings suggest
      that when speakers monitor their own utterances, they do not act as unbiased
      observers. Instead, they underestimate the ambiguity of their own utterances and
      overestimate the extent to which their disambiguating cues make their intention
      transparent. Such overestimation could be a systematic source of miscommunication
      in natural conversation, and should be accounted for by any theory of language
      production.

PMID- 12009040
TI  - Talis pater, talis filius: perceived resemblance and the belief in genetic
      relatedness.
AB  - People hardly ever realize that their belief in their high rate of success in
      detecting family resemblances is affected by their knowledge of the actual
      genetic link between individuals. In the three studies reported here, 100 men and
      100 women were requested to estimate the facial resemblance of photographically
      portrayed child-adult pairs, while being given either truthful or deceitful
      information, or no information, about their relatedness. Believing that the
      members of a pair were parent and offspring was the main predictor of the
      perceived similarity between them. Men and women agreed in judging children as
      more similar to female than to male adults, except when the pair members were
      believed to be related; in this case, men judged the child as resembling the
      alleged parents equally. Common remarks on family resemblance thus appear to
      ensue less from a conscious desire to please or reassure the parents than from
      general hypothesis-testing biases in human reasoning, made perhaps more specific
      in men by a concern with the problem of uncertain paternity.

PMID- 12009041
TI  - Procrastination, deadlines, and performance: self-control by precommitment.
AB  - Procrastination is all too familiar to most people. People delay writing up their
      research (so we hear!), repeatedly declare they will start their diets tomorrow,
      or postpone until next week doing odd jobs around the house. Yet people also
      sometimes attempt to control their procrastination by setting deadlines for
      themselves. In this article, we pose three questions: (a) Are people willing to
      self-impose meaningful (i.e., costly) deadlines to overcome procrastination? (b)
      Are self-imposed deadlines effective in improving task performance? (c) When self
      imposing deadlines, do people set them optimally, for maximum performance
      enhancement? A set of studies examined these issues experimentally, showing that
      the answer is "yes" to the first two questions, and "no" to the third. People
      have self-control problems, they recognize them, and they try to control them by
      self-imposing costly deadlines. These deadlines help people control
      procrastination, hit they are not as effective as some externally imposed
      deadlines in improving task performance.

PMID- 12009042
TI  - Breaking the barrier? Children fail to translate their preverbal memories into
      language.
AB  - We examined children's ability to translate their preverbal memories into
      language following a period of substantial language development. Children
      participated in a unique event, and their memory was assessed 6 months or 1 year
      later. At the time of the event and at the time of the test, their language
      skills were also assessed. Children of all ages exhibited evidence of verbal and
      nonverbal memory. Their language skills also improved over the delay. By the time
      of the test, children of all ages had acquired most of the vocabulary necessary
      to describe the target event. Despite this, they did not translate preverbal
      aspects of their memory into language during the test. In no instance did a child
      verbally report information about the event that was not part of his or her
      productive vocabulary at the time of encoding. We conclude that language
      development plays a pivotal role in childhood amnesia.

PMID- 12009043
TI  - Posthypnotic amnesia for autobiographical episodes: a laboratory model of
      functional amnesia?
AB  - Extreme variation in the accessibility of autobiographical memory is a major
      characteristic of functional amnesia. On the basis of its ability to temporarily
      disrupt the retrieval of memory material, posthypnotic amnesia (PHA) has been
      proposed as a laboratory analogue of such amnesia. However, most PHA research has
      focused on relatively simple, nonpersonal information learned during hypnosis.
      This experiment extended PHA to autobiographical memory by examining high- and
      low-hypnotizable subjects' explicit and implicit memory of two autobiographical
      episodes, one of which was targeted by a PHA suggestion. The effects of PHA were
      consistent with the major features of functional amnesia: PHA disrupted retrieval
      of autobiographical information, produced a dissociation between implicit and
      explicit memory, and was reversible. The nature of PHA's effect on
      autobiographical memory and the potential utility of a PHA paradigm for
      investigating functional amnesia are discussed.

PMID- 12009044
TI  - Overhearing a language during childhood.
AB  - Despite its significance for understanding of language acquisition, the role of
      childhood language experience has been examined only in linguistic deprivation
      studies focusing on what cannot be learned readily beyond childhood. This study
      focused instead on long-term effects of what can be learned best during
      childhood. Our findings revealed that adults learning a language speak with a
      more native like accent if they overheard the language regularly during childhood
      than if they did not. These findings have important implications for
      understanding of language-learning mechanisms and heritage-language acquisition.

PMID- 12009045
TI  - Infants and toddlers discriminate amount: are they measuring?
AB  - Four experiments that show an early ability to encode and retain information
      about extent are presented. We found that infants discriminate between the
      heights of dowels in a habituation task. We also found that toddlers discriminate
      between heights on a choice task in which a target dowel is presented and removed
      and they then choose between the target and a foil. Until 4 years of age,
      however, discrimination occurs only in the presence of a perceptually salient
      standard. Adults do not require a perceptually present standard; they can assess
      extent across temporal or spatial gaps by imposing a standard (measure). The
      present findings indicate that infants and toddlers do not possess an adult
      ability to establish extent, but that they do possess a skill that provides a
      start point for this important intellectual achievement.

PMID- 12009046
TI  - Expertise training with novel objects leads to left-lateralized facelike
      electrophysiological responses.
AB  - Scalp event-related potentials (ERPs) in humans indicate that face and object
      processing differ approximately 170 ms following stimulus presentation, at the
      point of the N170 occipitotemporal component. The N170 is delayed and enhanced to
      inverted faces but not to inverted objects. We tested whether this inversion
      effect reflects early mechanisms exclusive to faces or whether it generalizes to
      other stimuli as a function of visual expertise. ERPs to upright and inverted
      faces and novel objects (Greebles) were recorded in 10 participants before and
      after 2 weeks of expertise training with Greebles. The N170 component was
      observed for both faces and Greebles. The results are consistent with previous
      reports in that the N170 was delayed and enhanced for inverted faces at recording
      sites in both hemispheres. For Greebles, the same effect of inversion was
      observed only for experts, primarily in the left hemisphere. These results
      suggest that the mechanisms underlying the electrophysiological face-inversion
      effect extend to visually homogeneous nonface object categories, at least in the
      left hemisphere, but only when such mechanisms are recruited by expertise.

PMID- 12009047
TI  - Universality versus language-specificity in listening to running speech.
AB  - Recognizing spoken language involves automatic activation of multiple candidate
      words. The process of selection between candidates is made more efficient by
      inhibition of embedded words (like egg in beg) that leave a portion of the input
      stranded (here, b). Results from European languages suggest that this inhibition
      occurs when consonants are stranded but not when syllables are stranded. The
      reason why leftover syllables do not lead to inhibition could be that in
      principle they might themselves be words; in European languages, a syllable can
      be a word. In Sesotho (a Bantu language), however, a single syllable cannot be a
      word. We report that in Sesotho, word recognition is inhibited by stranded
      consonants, but stranded monosyllables produce no more difficulty than stranded
      bisyllables (which could be Sesotho words). Thisfinding suggests that the
      viability constraint which inhibits spurious embedded word candidates is not
      sensitive to language-specific word structure, but is universal.

PMID- 12009048
TI  - Femininity and fertility in sisters with twin brothers: prenatal androgenization?
      Cross-sex socialization?
AB  - Are sisters of twin brothers behaviorally or physiologically masculinized?
      Prenatal exposure to their brothers' androgens and postnatal socialization
      experiences unique to girls growing up with twin brothers might influence their
      attitudes, pubertal development, and reproductive histories. To investigate, we
      studied age- and cohort-matched samples of Finnish sisters from same-sex and
      opposite-sex twin pairs. Using data from two ongoing longitudinal studies of
      consecutive birth cohorts of Finnish twins, we assessed pubertal development at
      ages 11 and 14 and endorsement of attitudes associated with femininity at age 16.
      We also studied fertility in Finnish women from same- and opposite-sex twin pairs
      born from 1958 through 1971, obtaining information on their child-bearing
      histories when they were ages 15 to 28. Results of each comparison were
      unambiguously negative: There was no evidence of differences between sisters from
      same- and opposite-sex twin pairs, and thus, no evidence of either
      androgenization or cross-sex socialization.

PMID- 12009049
TI  - Infants of depressed mothers, although competent learners, fail to learn in
      response to their own mothers' infant-directed speech.
AB  - Depressed mothers use less of the exaggerated prosody that is typical of infant
      directed (ID) speech than do nondepressed mothers. We investigated the
      consequences of this reduced perceptual salience in ID speech for infant
      learning. Infants of nondepressed mothers readily learned that their mothers'
      speech signaled a face, whereas infants of depressed mothers failed to learn that
      their mothers' speech signaled the face. Infants of depressed mothers did,
      however, show strong learning in response to speech produced by an unfamiliar
      nondepressed mother. These outcomes indicate that the reduced perceptual salience
      of depressed mothers' ID speech could lead to deficient learning in otherwise
      competent learners.

PMID- 12009050
TI  - A visual equalization strategy for locomotor control: of honeybees, robots, and
      humans.
AB  - Honeybees fly down the center of a corridor by equating the speed of optic flow
      in the lateral field of the two eyes. This flow-equalization strategy has been
      successfully implemented in mobile robots to guide behavior in cluttered
      environments. We investigated whether humans use a similar strategy to steer down
      a corridor and determined the relative contributions of equating the speed of
      flow (.27), the splay angles of base lines (.62), and the visual angles of
      texture on the left and right walls (.03) to steering behavior. A generalized
      equalization strategy based on the weighted linear combination of these variables
      closely models human behavior, providing robust visual control.

PMID- 12009051
TI  - Grouping has a negative effect on both subjective contours and perceived
      occlusion at T-junctions.
AB  - Perceived occlusion of aligned T-junctions and subjective contours at implicit T
      junctions are often assumed to be related but are rarely examined with respect to
      common mechanisms. Using the method of paired comparison, we measured the
      strength of perceived occlusion at explicit T-junctions and the strength of
      subjective contours at implicit T-junctions (using different subjects) along the
      aligned edges of eight sets of inducer shapes. Sets varied in the similarity of
      component shapes with respect to orientation, height, width, and color With
      increasing shape similarity there was a striking decrease in both the strength of
      subjective contours and the strength of perceived occlusion; the correlation
      between these two kinds of judgments was .97. We conclude that common mechanisms
      underlie these two percepts and that edge alignment is a much stronger indicator
      of occlusion for poorly grouped than for strongly grouped inducers.

PMID- 12009052
TI  - Cuing interacts with perceptual load in visual search.
AB  - We tested the strong form of the perceptual-load hypothesis, which posits that
      the amount of perceptual load is the only factor determining whether attention
      can be effectively focused. Participants performed a visual search task under
      conditions of low and high load and with either a 100% valid spatial cue or no
      spatial cue. With no cue, participants showed evidence of processing to-be
      ignored stimuli when perceptual load was low but not when it was high, consistent
      with the perceptual-load hypothesis. However with a 100% valid spatial cue,
      participants showed little evidence of processing to-be-ignored stimuli, even
      when perceptual load was low. These results suggest that although perceptual load
      may be an important factor in attentional selectivity, load alone is not
      sufficient to explain how and when selective attention is effective.

PMID- 12009053
TI  - Source monitoring reduces the suggestibility of preschool children.
AB  - The relation between source monitoring and suggestibility was examined among
      preschool children. Thirty-two 3- to 5-year-olds were simultaneously presented
      with a brief story in two different modalities, as a silent video vignette and a
      spoken narrative. Each modality presented unique information about the story, but
      the information in the two versions was mutually compatible. The children were
      then asked a series of questions, including questions about the source (modality)
      of story details, and leading questions about story details (to assess
      suggestibility). Performance on the source-monitoring questions was highly
      correlated with the ability to resist suggestion. In addition, children who were
      asked source-monitoring questions prior to leading questioning were less
      susceptible to suggestion than were those who were asked the leading questions
      first. This study provides evidence that source monitoring can play a causal role
      in reducing the suggestibility of preschool children.

PMID- 12009054
TI  - Effects of financial incentives on the breakdown of mutual trust.
AB  - Disagreements between psychologists and economists about the need for and size of
      financial incentives continue to be hotly discussed. We examine the effects of
      financial incentives in a class of interactive decision-making situations, called
      centipede games, in which mutual trust is essential for cooperation. Invoking
      backward induction, the Nash equilibrium solution for these games is
      counterintuitive. Our previous research showed that when the number of players in
      the centipede game is increased from two to three, the game is iterated in time,
      the players are rematched, and the stakes are unusually high, behavior approaches
      equilibrium play. Results from the present study show that reducing the size of
      the stakes elicits dramatically different patterns of behavior. We argue that
      when mutual trust is involved, the magnitude of financial incentives can induce a
      considerable difference.

PMID- 12009055
TI  - Hepatobiliary inflammation, neoplasia, and argyrophilic bacteria in a ferret
      colony.
AB  - Hepatobiliary disease was diagnosed in eight of 34 genetically unrelated
      cohabitating pet ferrets (Mustela putorios furo) during a 7-year period. The
      eight ferrets ranged in age from 5 to 8 years and exhibited chronic
      cholangiohepatitis coupled with cellular proliferation ranging from hyperplasia
      to frank neoplasia. Spiral-shaped argyrophilic bacteria were demonstrated in
      livers of three ferrets, including two with carcinoma. Sequence analysis of a 400
      base pair polymerase chain reaction product amplified from DNA derived from fecal
      bacteria from one ferret demonstrated 98% and 97% similarity to Helicobacter
      cholecystus and Helicobacter sp. strain 266-1 , respectively. The clustering of
      severe hepatic disease in these cohabitating ferroes suggests a possible
      infectious etiology. The role of Helicobacter species and other bacteria in
      hepatitis and/or neoplasia in ferrets requires further study.

PMID- 12009056
TI  - Studies on pathogenesis following single and double infection with viral
      hemorrhagic septicemia virus and infectious hematopoietic necrosis virus in
      rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) were bath challenged with viral hemorrhagic
      septicemia (VHS) virus or infectious hematopoietic necrosis (IHN) virus or with
      both viruses simultaneously. The viral distribution and development of histologic
      lesions were examined using immunohistochemistry, while virus titer in kidney was
      determined by viral titration in cell culture. Single infections with VHS virus
      and IHN virus showed similar distributions of virus in internal organs. The early
      identification of virus in gill epithelium, 1 and 2 days postinfection (PI) for
      VHS virus and IHN virus, respectively, indicates that this organ is the point of
      entry for both viruses. The detection of VHS virus at 1 day PI and 3 days PI for
      IHN virus is indicative of kidney and spleen being the target organs for these
      viruses. A simultaneous infection of VHS virus and IHN virus resulted in both
      viruses establishing an infection. Further double infection did not result in a
      statistically significant lower titer of both viruses in kidney but a more
      restricted distribution of IHN virus in internal organs compared with the single
      infected group. The most striking finding is that, for IHN virus, virus was not
      detected in the brain in situ in the double-infected group. This study provides
      support for the conclusion that simultaneous infection with two piscine
      rhabdoviruses in a susceptible host results in some degree of interaction at the
      cell level, leading to a reduced systemic distribution of IHN virus.

PMID- 12009057
TI  - Inducible nitric oxide synthase and nitrotyrosine in listeric encephalitis: a
      cross-species study in ruminants.
AB  - Listeria monocytogenes (LM) is a Gram-positive facultative intracellular
      bacterium that causes fatal meningoencephalitis in humans and ruminants. A
      current paradigm predicts that intracellular bacteria are controlled by nitric
      oxide (NO) whose synthesis is catalyzed by inducible nitric oxide synthase
      (iNOS). The ability of macrophages (Mphi) to express iNOS shows extreme
      interspecies variability. Here the expression of iNOS and synthesis of NO was
      studied in listeric encephalitis of cattle, sheep, and goats. iNOS was expressed
      by a subset of Mphi in cerebral microabscesses in all three species. The level of
      iNOS expression and the density of cells per lesion expressing iNOS was highest
      in cattle, intermediate in sheep, and lowest in goats. The accumulation of
      nitrotyrosine (NT), an indicator of local NO synthesis, was observed in lesions
      of cattle but not in those of small ruminants. The density of iNOS-expressing
      cells in lesions was inversely correlated with the number of bacteria. No species
      differences were observed in regard to reactive oxygen intermediate (ROI)
      production by stimulated granulocytes, using the flow cytometric dihydrorhodamine
      123 (DHR) method indicating ROI generation. Thus, the marked species differences
      in iNOS expression, NT accumulation, and LM content in lesions of ruminants with
      listeric encephalitis are explained by different amounts of ROI produced. It
      suggests that variations in the ability of Mphi to synthesize NO are of
      pathophysiological significance in listeriosis.

PMID- 12009058
TI  - Morphologic and molecular characterization of Salmonella typhimurium infection in
      neonatal calves.
AB  - The host response to Salmonella plays a major role in the outcome of infection.
      The present study was undertaken to further characterize Salmonella typhimurium
      infection in neonatal calves at both the morphologic and the molecular level
      using the ligated ileal loop model. Eight 4-5-week-old male Holstein calves
      underwent laparotomy, and loops were prepared in the ileum. The loops were either
      inoculated with an S. typhimurium strain pathogenic for cattle or injected with
      sterile LB broth as control. Samples for histology, transmission and scanning
      electron microscopy, and RNA extraction were collected at various time points
      between 5 minutes and 12 hours postinfection. Invasion of both M cells and
      enterocytes began at 15 minutes postinfection. No specific cell type was the main
      target for invasion. Intracellular bacteria were observed in the lamina propria
      after 1 hour postinfection. A severe acute neutrophilic response was associated
      with invasion of the Peyer's patches. Upregulated expression of CXC chemokines
      (interleukin [IL]-8, growth-related oncogenes, [GRO] alpha and gamma, and
      granulocyte chemotactic protein [GCP]2) was detected by reverse transcription
      polymerase chain reaction beginning at 1 hour postinfection. Expression of
      proinflammatory (IL-1beta, IL-18, and tumor necrosis factor [TNF]alpha) and anti
      inflammatory (IL-10, IL-IRa, and IL-4) cytokines was also assessed. A marked
      increase in expression of IL-1beta was observed, whereas the profile of
      expression of IL-18 and TNFalpha did not change after infection. Upregulation of
      IL-1Ra and IL-4 but not of IL-10 was observed. These findings indicate that
      infection of bovine ligated ileal loops with S. typhimurium results in an acute
      neutrophilic inflammatory response that is associated with the upregulation of
      CXC chemokines (IL-8, GROalpha and gamma, and GCP2), IL-1beta, IL-IRa, and IL-4.

PMID- 12009059
TI  - Cats differ from mink and ferrets in their response to commercial vaccines: a
      histologic comparison of early vaccine reactions.
AB  - Early histologic changes in lesions at vaccine sites were compared in cats, mink,
      and ferrets. Twenty-four 4-month-old cats, 20 4-month-old mink, and 20 12-month
      old ferrets were vaccinated with three rabies virus vaccines, two feline leukemia
      virus vaccines, alum adjuvant, and saline. Injection sites were excised at
      selected time points up to 21 days postvaccination. Histologic examination of the
      tissue revealed significant differences among the cats, mink, and ferrets in the
      local response to the commercial vaccines. When compared with ferrets and mink,
      cats had more lymphocytes in response to all three rabies vaccines. Production of
      fibroblasts, collagen, and macrophages differed among the three killed aluminum
      adjuvanted vaccines in cats but did not differ significantly in mink or ferrets.
      Cats produced fewer binucleate cells than did mink or ferrets in response to the
      two adjuvanted leukemia virus vaccines. Differences seen in early tissue response
      of cats to commercial vaccines may be related to the increased predisposition of
      cats to vaccine-associated sarcomas.

PMID- 12009060
TI  - Interleukin 4-producing CD4+ T cells in the skin of cats with allergic
      dermatitis.
AB  - Lesional skin of cats with allergic dermatitis has a cellular infiltrate and a
      CD4/CD8 ratio comparable to that in humans with atopic dermatitis. CD4+ helper T
      cells and in particular cells belonging to the Th2 subset play an important role
      in disease pathogenesis in humans. We investigated the cytokine pattern of CD4+ T
      cells in situ, with special emphasis on the putative presence of cells producing
      interleukin 4 (IL4), in cats with allergic dermatitis. Immunohistochemical
      procedures were used to determine that CD4+ T cells in lesional and nonlesional
      skin of cats with allergic dermatitis can produce IL4, as occurs in humans.
      Lesional and nonlesional skin of cats with allergic dermatitis had significantly
      more IL4+ T cells (P = 0.001) than did skin of healthy control cats. Double
      staining indicated that all IL4+ cells were positive for pan-T or CD4 markers.
      Double labeling for mast cell chymase and IL4 stained primarily different cells.
      Western blotting demonstrated cross-reactivity between the antibody against human
      IL4 and a feline recombinant IL4. These results indicate that IL4 is primarily
      produced by CD4+ T cells and is also present in clinically uninvolved skin,
      indicating a role in the pathogenesis of allergic dermatitis in cats.

PMID- 12009061
TI  - Clinical, microscopic, and molecular aspects of canine leproid granuloma in the
      United States.
AB  - Leproid granulomas from seven dogs in the United States were evaluated. Gross
      characteristics included nodular and ulcerated dermal and subcutaneous lesions
      primarily on the caudal aspects of the pinnae and to a lesser extent on the
      muzzle, face, and forelimbs. In all except one dog, there was complete regression
      of the lesions within 6 months, either with no therapy or after surgical
      resection. Cytology or histopathology revealed pyogranulomatous inflammation with
      few to many acid-fast mycobacterial bacilli within macrophages. The organisms
      could not be cultivated in vitro. DNA sequencing of part of the 16S ribosomal RNA
      gene region revealed 99-100% homology among fragments from five of these dogs and
      fragments from dogs in the south Pacific. This syndrome occurs in dogs in North
      America and the prognosis is excellent, in contrast to the prognosis for rapid
      growing or tuberculous mycobacteriosis.

PMID- 12009062
TI  - Prognostic significance of a new histologic grading system for canine
      osteosarcoma.
AB  - Histologic grade is an important determinant in clinical outcome of human
      osteosarcoma (OS). In this study, the histologic characteristics of primary and
      metastatic canine OS were evaluated using a new classification system. Histologic
      characteristics were classified in 166 primary and 34 metastatic canine OS.
      Prognostic variables for clinical outcome were determined using multivariate
      analysis. Most OS were histologically characterized by severe to extreme cellular
      pleomorphism, a variable number of mitoses, small to moderate amounts of matrix,
      a high percentage of tumor cells, and minimal to moderate amounts of necrosis.
      Tumor invasion into vessels was present in 117/152 (71%) tumors, and 12/50 (24%)
      of the regional lymph nodes had evidence of metastasis. Classification of the 166
      tumors resulted in seven (4%) grade 1, 34 (21%) grade II, and 125 (75%) grade III
      OS. In the multivariate analysis, histologic grade III OS and elevated
      pretreatment plasma alkaline phosphatase (AP) levels were independent predictors
      of clinical outcome. Dogs with high-grade tumors and elevated AP should be
      carefully evaluated for the presence of metastatic disease before starting
      adjunctive therapy protocols.

PMID- 12009063
TI  - Immunolocalization of the smooth muscle-specific protein calponin in complex and
      mixed tumors of the mammary gland of the dog: assessment of the morphogenetic
      role of the myoepithelium.
AB  - The immunohistochemical expression of the smooth muscle-specific protein calponin
      was studied to assess the contribution of myoepithelial cells to the histogenesis
      of spindle cells of complex and mixed tumors of the mammary gland of the dog and
      the origin of cartilage and bone in mixed tumors. Formalin-fixed tissues from 55
      benign and malignant tumors (49 also containing surrounding normal mammary gland)
      were evaluated. Periacinar and periductal myoepithelial cells of all the 49
      normal mammary glands were diffusely stained by the anti-human calponin
      monoclonal antibody. Calponin was found in 53 (98%) of the tumors studied,
      reacting with the myoepithelium-like cells of 86% of benign tumors and their
      remnants in 85% of malignant tumors. Five different types of calponin
      immunoreactive myoepithelial cells were identified: hypertrophic myoepithelial
      cells. fusiform cells, stellate myoepithelial cells, rounded (myoepithelial)
      cells, and chondroblasts. Differences in staining intensity and staining pattern
      among these five types of cells suggested a transition of myoepithelial cells to
      chondroblasts. Stromal myofibroblasts also showed calponin immunoreactivity, but
      they did not react with a cytokeratin 14 monoclonal antibody, which recognizes
      myoepithelial cells in mammary gland. Calponin appears to be a very sensitive
      marker of normal and neoplastic myoepithelium in the canine mammary gland, and
      its identification in different cell types of complex and mixed tumors of the
      mammary gland of the dog suggests a major histogenetic role for myoepithelial
      cells.

PMID- 12009064
TI  - Trichinella nativa and T. spiralis induce distinguishable histopathologic and
      humoral responses in the raccoon dog (Nyctereutes procyonoides).
AB  - Three experimental groups of six male raccoon dogs (Nyctereutes procyonoides)
      each were formed by placing one of three littermates from six litters into each
      group. One group was inoculated with pig-origin Trichinella spiralis, the second
      was inoculated with raccoon dog-origin T. nativa, and the third served as a
      control group. The infective dose was 1,000 larvae/kg of body weight. Every third
      week, biopsies from M. triceps brachii were taken, and serum samples were
      collected for up to 12 weeks postinfection. In the early phase of the infection,
      cysts of both parasites were elongated cylinders that later became more
      spherical. However, at the end of the experiment, the cysts of T. nativa were
      more rounded than those of T. spiralis (mean length/width = 2.5 versus 1.5 in T.
      spiralis versus T. nativa, respectively). Both species accumulated a collagen
      rich capsule around the nurse cell, but the capsule was thicker in T. nativa. In
      both parasites, the total surface area of the sagittal section of the cyst was
      equal. Inflammation was more intense around T. nativa cysts. Specific antibodies
      were recognizable 2 weeks after infection by both enzyme-linked immunosorbent
      assay (ELISA) and western blot. In western blots, serum from both T. nativa- and
      T. spiralis-infected animals recognized the same components, but reaction with
      the homologous antigen was stronger. The same pattern was also seen in the ELISA.
      Immunoreactive epitopes were localized only in internal organs and cuticula of
      larvae in muscle.

PMID- 12009065
TI  - Metastatic lymphangiosarcoma in a horse.
AB  - A lymphangiosarcoma with metastases was found in a horse that presented with
      respiratory distress and edema in the ventral thorax and abdomen. The necropsy
      revealed diffuse edema in the subcutaneous connective tissue. Mediastinal,
      mesenteric, iliac, and renal lymph nodes were enlarged and white with soft,
      yellowish necrotic areas. Histologic examination revealed numerous channels and
      disorganized vessels lined by large polyhedral, polymorphic cells. Tumor
      metastases were observed in the spleen, lungs, and kidneys. Immunohistochemical
      evaluation of the tumor cells demonstrated positive staining for factor VIII,
      vimentin, and keratin. Laminin was scarce, and collagen IV staining was negative,
      consistent with a discontinuous or absent basement membrane.

PMID- 12009066
TI  - Encephalomyelitis associated with akabane virus infection in adult cows.
AB  - Between August and September 2000, five 2-7-year-old cows in Korea exhibited
      neurologic signs and were diagnosed as infected with Akabane virus based on the
      results of histopathology, immunohistochemistry, serology, and reverse
      transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemistry
      and RT-PCR were equally effective and sensitive for diagnosing Akabane virus
      infection during the early stage of infection. Typical lymphohistiocytic
      inflammation characterized by perivascular mononuclear cell infiltration,
      gliosis, neuronophagia, and neuronal loss was noted in the brain and the ventral
      horn gray matter of the spinal cord. The lesions in the brain were most prominent
      in the pons and medulla oblongata. Akabane virus antigen was detected in the
      brain and spinal cord, mainly in degenerating neurons and glial cells. RT-PCR
      analysis revealed a target band of expected size in four cows. This is the first
      report on an outbreak of natural Akabane virus infection in adult cattle.

PMID- 12009067
TI  - Cutaneous vasoproliferative lesions in goats.
AB  - Abstract. In a retrospective survey of caprine neoplastic disease, eight masses
      were diagnosed as cutaneous vascular tumors. The typical clinical presentation
      was a solitary raised, bleeding mass. No predilection with regard to age, breed,
      sex, or anatomic location was found. Reevaluation of the microscopic features of
      the masses resulted in diagnoses of hamartoma (2), hemangioma (4), and
      hemangiosarcoma (2). An endothelial cell origin was confirmed in all seven tumors
      tested immunohistochemically for factor VIII-related antigen. Although rarely
      reported, goats display a range of cutaneous vascular growth abnormalities
      similar to those observed in other domestic animals.

PMID- 12009068
TI  - Complex polysaccharide inclusions in skeletal muscle adjacent to sarcomas in two
      dogs.
AB  - Inclusions of periodic acid-Schiff-positive, amylase resistant material were
      found within skeletal muscle fibers adjacent to an osteosarcoma in the proximal
      femur of an 8-year-old intact female Cocker Spaniel dog (dog No. 1) and adjacent
      to a synovial cell sarcoma of the stifle joint in a 7-year-old spayed female
      Bouvier des Flandres dog (dog No. 2). Inclusions were pale blue-gray with
      hematoxylin and eosin stain and formed irregular inclusions, replacing up to
      approximately 80% of the fiber diameter. Inclusions from dog No. 2 were of non
      membrane-bound granular to filamentous material that occasionally formed
      discrete, elongate electron-dense masses. The features of these inclusions were
      similar to those of materials previously described as complex polysaccharide,
      polyglucosan bodies, amylopectin, and Lafora bodies. Evidence for a generalized
      metabolic disorder was not found in these two dogs, suggesting that storage of
      complex polysaccharide can occur as a relatively nonspecific response to
      metabolic alterations in skeletal muscle in a variety of conditions.

PMID- 12009069
TI  - Mixed apocrine sweat gland tumor of the tail in a cow.
AB  - A 4-year-old native-breed cow had a mass with wide areas of ulceration and
      hemorrhage at the base of the tail at the same level as the vulva. The tumor was
      19 X 13 X 11 cm, appeared red-brown, and was firm to hard, with gritty areas
      apparent on cut surface. Histologically, the tumor mass was composed of
      multilayered epithelial cells forming glandular structures with occasional apical
      blebs and rare solidly packed cells in nests. The stroma included fibrous
      connective tissue, scattered or periglandular sheets of spindle-shaped cells
      resembling myoepithelium, several cartilaginous formations, and numerous
      irregular islands of mineralized osteoid, well-formed bone trabeculae lined by
      osteoblasts, and many osteoclast-like multinucleated giant cells among or near
      the neoplastic epithelium. Immunohistochemically, the neoplastic epithelium was
      positive for pan-cytokeratin (AE1/AE2) and cytokeratin 19 but was negative for
      cytokeratin 18. Spindle-shaped cells were stained with alpha smooth muscle actin
      (alphaSMA) and to a lesser extent vimentin antibodies. The cells of osteogenic
      lineage and spindle cells closely associated with the osteoid showed strong
      immunostaining for vimentin but not for alphaSMA. Immunostaining for neuron
      specific enolase and S100 protein was not observed in any component of the tumor
      mass. These findings suggested that the origin of bone formation was
      undifferentiated mesenchymal cells with osteogenic potential.

PMID- 12009070
TI  - Angiolipomatous tumors in dogs and a cat.
AB  - Variants of lipoma are uncommon, although fibrolipoma and infiltrative lipoma
      have been well documented. This report describes two cases of rare angiolipoma in
      dogs and the first documentation of angiofibrolipoma and infiltrating angiolipoma
      in a cat and a dog, respectively. Tumors were solitary, and most were located on
      the thorax of middle-aged patients. Angiolipomas were composed of mature adipose
      tissue mixed with variable numbers of blood vessels. In addition to the adipose
      and vascular components, the angiofibrolipoma contained bundles of collagenous
      connective tissue. The infiltrative angiolipoma had a primary mass external to
      the muscle and was histologically similar to a mixed intramuscular hemangioma
      that was confined to the muscle. Both disrupted bundles of striated muscle and
      were associated with segmental degeneration and loss of myofibers.

PMID- 12009071
TI  - Pattern of sensitization to common environmental allergens amongst atopic
      Singapore children in the first 3 years of life.
AB  - This study was aimed to investigate the sensitization pattern to a range of
      common allergens in young Singaporean children. A cross-sectional study involving
      75 children aged below 3 years was carried out. They presented between December
      1995 and April 2000 with symptoms of asthma, rhinitis, eczema, or food allergy.
      Their levels of allergen-specific serum IgE to a panel of foods (egg white, milk,
      soy protein, shrimp, wheat and peanut), pet dander, dust mites and cockroaches
      were measured with Pharmacia CAP System radioallergosorbent test kits. Serum IgE
      levels greater than 0.35 kU/l represented a positive result. Four children could
      not be tested with the complete panel because of insufficient serum. The
      prevalence of sensitization was highest for cow's milk (45.9%) followed by egg
      white (38.7%), dust mites Dermatophagoides pteronyssinus (31.4%) and Blomia
      tropicalis (25.5%). Sensitization to ingested allergens was significantly more
      prevalent in children aged 1 year or younger than in the older children (70.4% of
      those below 1 year, and 50% of those aged 1-3 years; p < 0.02). Sensitization to
      inhaled allergens, such as dust mites, was more likely to manifest as respiratory
      symptoms (allergic rhinitis and asthma), while ingested allergens were associated
      with gastrointestinal symptoms and eczema (p < 0.001). It was concluded that
      infants and young children are at high risk of sensitization to common
      environmental substances. Allergen avoidance is therefore important even in the
      very young. The prevalence of sensitization to food allergens is higher compared
      to inhalant allergens in young children.

PMID- 12009072
TI  - Allergic rhinitis in Rosa domescena cultivators: a novel type of occupational
      allergy?
AB  - After the diagnosis of allergic rhinitis due to Rosa domescena was suspected in
      one subject with skin prick and nasal provocation tests, we recruited all other
      workers employed in rose cultivation in Yakaoren village, Isparta. From May 2000
      to July 2000 (exposure period 'time of rose handling'), we studied 600
      individuals employed in rose cultivation. A questionnaire was administered by a
      physician, and skin testing was done by a nurse on 75 individuals suffering from
      asthma and/or rhinitis. Sera from these 75 subjects were available for
      immunologic testing. The diagnosis of atopy against rose was based on the
      presence of work-related symptoms, positive skin prick test (SPT) with rose
      extracts, and positive RAST. While no subject reported asthmatic symptoms, twenty
      of them reported either rhino-conjunctivitis, rhinitis or both on exposure to
      Rosa domescena. Fourteen of these subjects had increased specific IgE levels to
      Rosa domescena. Eleven (78.5%) also had a positive skin reaction to Rosa
      domescena. Out of the six negative sera with normal specific IgE levels to rose,
      only two (33.3%) had positive skin reactivity. No subject had significant daily
      peak expiratoy flow rate (PEFR) variations. We conclude that exposure to Rosa
      domescena may represent a risk for allergic rhinitis. The possibility of an
      occupational rose allergy should therefore be taken into consideration in the
      subjects working in rose cultivation.

PMID- 12009073
TI  - Allergic conjunctivitis.
AB  - The purpose of this research is to study the clinical features and risk factors
      of various types of allergic conjunctivitis. Four hundred and forty-five patients
      with a history of itching, foreign body sensation, lacrimation and red eyes were
      examined, and a skin test was performed and assessed to grade the severity. The
      mean age of the subjects was 24.5 +/- 16.3 years with female preponderance,
      except for vernal keratoconjunctivitis. The majority of the patients had
      perennial allergic conjunctivitis. Ninety-five percent of the patients had
      associated allergic diseases, especially allergic rhinitis. Sixty-six percent of
      the patients had a family history of atopy. Most patients had symptoms at night.
      Symptoms persisted throughout the year and were generally triggered by exposure
      to house dust. The allergy skin tests to common aero-allergens were positive in
      95% of patients tested. Common allergens causing sensitization were house-dust
      mites, house dust, cockroaches, and grass pollen. Environmental control and
      avoidance of these allergens should be stressed in the management of these
      conditions.

PMID- 12009074
TI  - Affinity purified oval antigen for diagnosis of Opisthorchiasis viverrini.
AB  - Monoclonal antibodies (MAb) were raised against an oval antigen of the liver
      fluke Opisthorchis viverrini which is the causative agent of a parasitosis, i.e.
      opisthorchiasis in Thailand. The antibodies were used in an affinity column to
      purify the O. viverrini oval antigen from a crude extract of adult parasites by
      chromatography. The oval antigen was then used in a membrane (dot) ELISA for
      detecting antibodies in serum samples of parasitologically confirmed Opisthorchis
      viverrini infected individuals (adult parasites were found in stools after
      praziquantel treatment and salt purgation), as well as of individuals infected
      with other parasites and parasite-free controls. The MAb-based dot-ELISA using
      the affinity purified O. viverrini oval antigen revealed 100% sensitivity,
      specificity and accuracy for detecting O. viverrini infection. The test is
      simple, rapid and highly reproducible. Several samples can be tested at the same
      time without the requirement for special equipment or much increase in testing
      time; thus it is suitable for mass screening for O. viverrini exposure,
      especially in new endemic areas. Furthermore using serum specimens could increase
      patient and community compliance compared to the conventional parasitological
      survey which uses stool samples for the detection of O. viverrini ova, without
      treatment and subsequent salt purgation, this conventional method shows a low
      sensitivity and is also unpleasant to both the sample donors and the laboratory
      technicians which has historically shown a further negative impact on the final
      outcome.

PMID- 12009075
TI  - Virological, immunological and host factors in HIV-1 discordant couples in
      Thailand.
AB  - The potential factors of resistance to HIV-1 infection were investigated in 23
      HIV discordantly infected couples, of each, one partner had HIV infection and the
      matched spouse was not infected. Both partners of the HIV discordant couples
      possessed comparable number of CD4+ cells expressing CCR5. Our study demonstrated
      that resistance to HIV-1 infection was not due to low level of HIV viral load in
      their infected-matched spouses. In addition, selective biological phenotype of
      HIV clinical isolates, which is indicative for risk of transmission, could not be
      determined in this study. However, we have demonstrated that the unknown genetic
      factor(s), and neutralizing antibody of broad and high activity could be taken
      into an account for resistance to HIV infection in the HIV discordant couples.

PMID- 12009076
TI  - Immunoblot evaluation of the specificity of the 29-kDa antigen from young adult
      female worms Angiostrongylus cantonensis for immunodiagnosis of human
      angiostrongyliasis.
AB  - The antigenic components of Angiostrongylus cantonensis young adult female worm
      somatic extract (FSE) were revealed by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and immunoblotting. The sera tested were from patients
      with proven angiostrongyliasis, other parasitic diseases, and healthy adults.
      Both the sera and cerebrospinal fluid (CSF) were tested from patients with
      clinical angiostrongyliasis. The CSF from patients with other neurological
      diseases were also included. Using SDS-PAGE, we found that the FSE comprised more
      than 30 polypeptides. Immunoblot analysis revealed at least 12 or 13 antigenic
      bands in patients with proven or clinical angiostrongyliasis, respectively. The
      patterns of reactivity recognized by the serum and CSF antibodies against FSE
      were similar. These antigenic components had molecular masses ranging from less
      than 14.4 to more than 94 kDa. The prominent antigenic band of 29-kDa might serve
      as a reliable marker for the diagnosis of angiostrongyliasis. The sensitivity,
      specificity, positive and negative predictive values of immunoblot analysis in
      this antigenic band were 55.6%, 99.4%, 83.3% and 97.4%, respectively.

PMID- 12009077
TI  - The TGF beta receptor endoglin in systemic sclerosis.
AB  - Immunohistochemical, flow cytometric and ELISA studies were performed to examine
      the expression of endoglin (CD105, a TGF beta receptor) on dermal endothelial
      cells, peripheral blood monocytes and free and bound serum levels in patients
      with systemic sclerosis as compared with appropriate controls. Endoglin was found
      to be significantly upregulated on dermal blood vessels in patients with
      scleroderma (and in patients with inflammatory skin disorders) as compared to
      healthy skin (p < 0.05). In contrast, there was no significant difference in
      endoglin expression on circulating blood monocytes between scleroderma patients
      and patients with a rheumatic disoder or healthy control subjects; however,
      endoglin expression was upregulated on monocytes in inflammatory joint fluid from
      patients with rheumatoid arthritis. Endoglin expression on monocytes was also
      influenced by isolation techniques and during whole blood culture. No differences
      were found in circulating free or bound endoglin levels between scleroderma
      patients and healthy controls. In conclusion, endoglin expression on dermal
      endothelial cells was significantly enhanced in scleroderma but levels on
      circulating monocytes and in the serum were within normal limits. The functional
      significance of this upregulation is uncertain but may reflect endothelial
      activation in scleroderma.

PMID- 12009078
TI  - Fatal buckwheat dependent exercised-induced anaphylaxis.
AB  - Cases of food-dependent exercise-induced anaphylaxis (FEA) caused by buckwheat
      have been rare. Clinical, laboratory, and autopsy findings are present on an 8
      year old girl with FEA caused by Japanese buckwheat. The patient consumed
      buckwheat noodles called "zaru soba" and immediately thereafter swam vigorously.
      Approximately 30 minutes later, she complained of abdominal pain, vomiting,
      coughing, and chest discomfort. Another ten minutes later her consciousness level
      deteriorated and she experienced cardiorespiratory arrest. The heart beat was
      restored and she was admitted to the hospital. She never regained consciousness
      and expired after another arrest 13 days later. Her IgE level was high (2,840
      IU/ml) and the IgE-radioallergosorbent test (RAST) score was 2 for soybeans, 3
      for buckwheat, 2 for rice, and 3 for wheat. An exaggerated hematemesis that
      occurred immediately after hospital admission indicated an inflammatory condition
      of the digestive tract that was caused by buckwheat. Marked ulceration
      accompanied with hemorrhage and necrosis was noted at the ileum. Extensive
      hemorrhage involving the endotracheal pulmonary field and lymphocyte infiltration
      of the alveolar space likely appeared after the inflammation. The analysis of
      buckwheat-specific IgE antibody by immunoblotting showed 7 bands that reacted
      with the IgE of the patient's serum, 4 bands: 16, 20, 24, and 58 kDa, were
      specific to the patient as compared to subjects not allergic to buckwheat. A
      first case of fatal FEA by buckwheat is reported with reference to specific IgE.

PMID- 12009079
TI  - Nasal septal perforation in a patient with allergic bronchopulmonary
      aspergillosis and rhinitis on long term corticosteroids.
AB  - A 22-year-old male, referred to us as a case of multi-drug resistant tuberculosis
      was diagnosed as allergic bronchopulmonary aspergillosis (ABPA) after serological
      and computed tomography confirmation. He was initiated on oral as well as inhaled
      corticosteroids along with nasal corticosteroid spray for his nasal complaints.
      One year subsequently, he developed a nasal septal perforation. Biopsy taken from
      the site did not reveal any granulomatous or atrophic changes and cultures of the
      biopsy did not yield any organism. The septal defect, repaired surgically by
      Hazeltine's method healed completely within 6 weeks. There have been anecdotal
      reports of septal perforation in patients with rhinitis on intranasal
      corticosteroids but hitherto not in patients with ABPA. A periodic examination of
      the nasal septum should be undertaken in patients with ABPA and rhinitis on long
      term inhaled oral and intranasal corticosteroids along with oral corticosteroids.

PMID- 12009080
TI  - Toxoplasma gondii antibodies in HIV and non-HIV infected Thai pregnant women.
AB  - Serological evidence for Toxoplasma gondii infection in Thai pregnant women was
      investigated. One thousand six hundred and sixty-nine blood specimens were
      collected from 838 HIV-seropositive and 831 HIV-seronegative pregnant women
      attending the antenatal-care clinic at Siriraj Hospital, Bangkok, Thailand,
      during a two-year period. Toxoplasma IgG antibody was detected, using a solid
      phase enzyme-linked immunosorbent assay in which the membrane protein p-30 was
      the predominant antigen. IgG positive sera were subsequently examined for IgM
      antibody by the capture antibody enzyme immunoassay. The IgG antibody was found
      in 450 (53.7%) HIV seropositive women and 44 (5.3%) non-HIV infected women, with
      a statistically significant difference (p < 0.0001). Three of the 450 HIV
      seropositive and 2 of the 44 HIV-seronegative sera with IgG antibody were
      positive for IgM antibody against T. gondii. This result suggested that HIV
      seropositive pregnant women had a higher risk of Toxoplasma infection with
      increase exposure to their offspring.

PMID- 12009081
TI  - The role of leukodepletion in limiting ischemia/reperfusion damage in the heart,
      lung and lower extremity.
AB  - This article describes the experimental infrastructure and subsequent clinical
      application of a comprehensive reperfusion strategy to limit the injury following
      ischemia, resulting in an improvement in post operative organ function. In
      particular, it examines the role of luekodepletion in minimizing damage and
      improving functional outcome in the heart, lung and lower extremity. During
      cardiothoracic procedures, various organs can be subjected to temporary ischemia,
      particularly the heart (cardioplegic arrest), lung (transplant), and lower
      extremity (femoral canulation, IABP). The background of ischemia/reperfusion
      injury is discussed as it applies to each of these 3 organs, as well as findings
      that ischemia followed by reperfusion results in a similar injury in each organ.
      Data are then presented to demonstrate that a comprehensive reperfusion strategy,
      utilizing a modified substrate-enriched blood reperfusate delivered at a low
      pressure can limit this injury, and that adding white blood cell filtration
      significantly improves the efficacy of this approach. These principles have now
      been used in a series of patients undergoing various surgical procedures with
      excellent results. Application of these concepts may significantly improve the
      outcome in patients undergoing procedures which subject these organs to temporary
      ischemia.

PMID- 12009082
TI  - Hemofiltration and inflammatory mediators.
AB  - Hemofiltration used in conjunction with cardiac surgery and cardiopulmonary
      bypass (CPB) was first reported in 1976. Since then, the technology has been
      routinely used in this context. This review attempts to restate the basic
      principles governing hemofiltration, the strategies or timing of the use of the
      technology, and the indications. Particular attention will be focused on the role
      of hemofiltration in an attempt to reduce the plasma levels of some of the
      mediators of the Systemic Inflammatory Response Syndrome (SIRS).

PMID- 12009083
TI  - The rationale for fat filtration during cardiac surgery.
AB  - Improved filter technology may enable the removal of specific substances such as
      lipids from the blood. Lipids form a heterogeneous group of compounds, but during
      surgery, the main interest is focussed on triglycerides, glycerol and free fatty
      acids. Fat emboli have been demonstrated in the brain after cardiac surgery and
      are associated with ischaemic brain injury. Fat emboli have also been
      demonstrated in lung and kidney tissue. Lung tissue and leucocytes are especially
      vulnerable to the effects of free fatty acids. The surgical wound suction blood
      during cardiac surgery contains a considerable quantity of microemboli.
      Therefore, as a first step to determining the place of fat filtration during
      cardiac surgery, the use of a fat removal filter for surgical wound suction blood
      is advocated.

PMID- 12009084
TI  - Intraoperative treatment strategy to reduce the incidence of postcardiopulmonary
      bypass atrial fibrillation.
AB  - PURPOSE: Postcardiopulmonary bypass atrial fibrillation remains a constant
      complication associated with coronary revascularization, the incidence of which
      occurs from 20% to 35%. Previous studies have addressed this problem in the
      postoperative setting utilizing pharmacological agents, but the results have been
      variable. The purpose of this study was to evaluate a novel intraoperative
      strategy to reduce the incidence of postcardiopulmonary bypass atrial
      fibrillation. We theorized that leukocyte depletion by filtration with the
      addition of aprotinin would reduce the systemic inflammatory effects of bypass
      and reduce the incidence of atrial fibrillation. METHODS: One hundred and twenty
      two patients participated in this randomized study. Only isolated primary
      coronary revascularization procedures on cardiopulmonary bypass were included.
      The control group (n=55) received standard moderate hypothermic blood
      cardioplegia cardiopulmonary bypass. The treatment group (n=65) received similar
      cardiopulmonary bypass with the addition of strategic leukocyte depletion with
      Pall Biomedical Products (East Hills, NY) leukodepletion filters and full-dose
      aprotinin. RESULTS: The intraoperative addition of leukocyte depletion by
      filtration with aprotinin reduced the incidence of postcardiopulmonary bypass
      atrial fibrillation by 72%. The incidence.of atrial fibrillation in the control
      group was 27% (15 of 55). In contrast, the occurrence of atrial fibrillation in
      the treated group was only 7.6% (5 of 65) (p<0.025). CONCLUSIONS: This novel
      intraoperative treatment strategy of both mechanical (leukocyte filtration) and
      pharmacological (aprotinin) intervention appears to markedly reduce the incidence
      of postcardiopulmonary bypass atrial fibrillation. To our knowledge, this is the
      first study to combine these two treatment strategies. A previous study has noted
      a decline in atrial fibrillation with aprotinin in the animal model, but not to
      the extent observed in our study. The beneficial effects of the reduction of
      atrial fibrillation include reduced risk of emboli formation and the incidence of
      ischemia in the heart, lung and brain. In addition, a decrease in length of
      hospital stay, recovery time and overall cost occurred.

PMID- 12009085
TI  - In vitro performance characteristics of a high-flux hemodialyzer with a novel
      polyester-polymer-alloy (PEPA) membrane.
AB  - Despite improvements in hemodialyzers with respect to their clearance of middle
      and high molecular mass molecules, accumulation of specific solutes in the
      circulation of dialysis patients continues to be a medical problem. A new
      membrane material, polyester-polymer alloy (PEPA) which has been developed to
      have a filtration profile akin to that of the natural kidney, is now being used
      in hemodialyzers. This study evaluates the performance of a PEPA-based
      hemodialyzer alongside a selection of available competing high-flux dialyzers
      using official standardized methods. The new membrane material appears to be a
      viable alternative which offers performance at least as good as that of the
      competition. The promising results obtained with the PEPA membrane suggest that a
      detailed clinical performance study should be undertaken.

PMID- 12009086
TI  - Selective granulocyte/monocyte apheresis in the treatment of HIV-infected
      patients: short-term and long-term effects on immunological and virological
      parameters.
AB  - CD4 T cells constitute the major cellular target of HIV infection and, in the
      natural evolution of the disease, are gradually lost, leading to severe
      immunodeficiency. Highly active antiretroviral therapy (HAART) is generally
      effective in reducing HIV replication to undetectable levels and allows the
      recovery of CD4 T cells in the majority of patients treated. However, some
      sanctuaries of HIV replication persist even after years of effective HAART and
      are responsible for the rebound of viral replication when treatment is
      interrupted. Monocytes/macrophages are also infectable by HIV and are less
      susceptible to its cytopathic effects compared to CD4 T cells. Replication
      competent HIV DNA is detectable in peripheral monocytes of patients under HAART.
      These cells may therefore contribute to the maintenance of HIV replication during
      treatment. In addition, both monocytes and granulocytes are abnormally activated
      during HIV infection and this results in overproduction of some pro-inflammatory
      cytokines, among them TNF-alpha. For these reasons we tested whether the renewal
      of the pool of circulating monocytes and granulocytes by selective apheresis (G1
      apheresis) could influence some key immunological and virological parameters in
      HAART-treated patients. The results showed that treatment with G1 apheresis
      without discontinuation of HAART results in an accelerated immune reconstitution
      with sustained increases in CD4 T cell counts in those patients who respond
      virologically to HAART. G1 apheresis is also followed by a strong reduction of
      TNF-alpha and a reduction of cells bearing integrated HIV DNA. Taken together,
      the results indicate that G1 apheresis could be used to improve the immunological
      and virological response to HAART.

PMID- 12009087
TI  - Leukocyte filtration in lung transplantation.
AB  - Controlled reperfusion of the transplanted lung has been used in nine consecutive
      patients to decrease manifestations of lung reperfusion injury. An extracorporeal
      circuit containing a roller pump, heat exchanger and leukodepleting filter is
      primed with substrate-enhanced reperfusion solution mixed with approximately 2000
      ml of the patient's blood. This solution is slowly recirculated to remove
      leukocytes prior to reperfusion. When the pulmonary anastomoses are completed,
      the pulmonary artery is cannulated through the untied anastomosis using a
      catheter containing a pressure lumen for measurement of infusion pressure. An
      atrial clamp is left in place on the patient's native atrial cuff to decrease the
      risk of systemic air embolism during the brief period of reperfusion from the
      extracorporeal reservoir. During reperfusion, the water bath to the heat
      exchanger is kept at 35 degrees C and the flow rate for reperfusion solution is
      between 150 and 200 m/min, keeping the pulmonary artery pressure <14 mmHg. Eight
      of nine patients were ventilated on 40% inspired oxygen within a few hours of
      operation and 7/9 were extubated on or before postoperative day 1. Six of nine
      patients are long-term survivors.

PMID- 12009088
TI  - Neuroprotection during cardiac surgery: strategies to reduce cognitive decline.
AB  - Although the population receiving cardiac surgery is older and therefore more
      prone to cognitive deterioration, these difficulties have declined over the last
      ten years. It is likely that the multiple changes introduced to cardiac surgery
      over time have had a cumulative benefit in protecting the brain. The most likely
      causes of cognitive difficulties are microemboli delivered to the brain during
      surgery, altered cerebral perfusion and an inflammatory response. The
      interventions that have been implemented can be divided into those which have
      attempted to reduce the potential causes of damage and those aimed at reducing
      the impact by attempting to protect the brain. The evidence for three main types
      of intervention (equipment, techniques and drugs) is reviewed in this paper.
      Although many interventions are available only a few have shown a clear benefit.
      Progress in the future will require larger studies to address this multifactorial
      problem.

PMID- 12009089
TI  - The inflammatory response to CPB: the role of leukocyte filtration.
AB  - Leukocyte activation is a significant component of the systemic inflammatory
      response to cardiopulmonary bypass (CPB). Various strategies have been developed
      aiming to reduce leukocyte activation and its deleterious effects on organ
      function after cardiac surgery. Leukocyte filtration aims to physically remove
      activated leukocytes from the circulation during CPB. The technique has been used
      since the mid-1990s but its efficacy in attenuating the effects of inflammatory
      response remains controversial. This article presents a review of published
      trials investigating the effects of leukocyte filtration on humans undergoing
      cardiac surgery.

PMID- 12009090
TI  - Gene targeting technology and advances in the pathophysiology of inflammation.
AB  - Gene targeting ('knock-out') technology is now widely used in the basic science
      of all disciplines of pathology and particularly auto-immune and inflammatory
      disease. Gene targeting is the wilful introduction of precise mutations into the
      genome of an animal, usually a mouse, affecting the function of a single gene or
      genes. The phenotyping of knockout mice provides whole animal data on the
      functions of individual genes in pathophysiological settings, and frequently
      provides the basis for novel therapeutic strategies. 'Knock-ins', the Cre-LoxP
      system and conditional knockouts are important new advances. This paper serves as
      an introduction to the methodology and draws on examples of major advances in
      inflammation research provided by the targeting of cytokines, in particular the
      tumour necrosis factor family of ligands.

PMID- 12009091
TI  - Laboratory diagnosis of influenza virus infection.

PMID- 12009092
TI  - Standardisation of ANCA testing across Australasian laboratories: impact of the
      International Consensus Statement.

PMID- 12009093
TI  - Medical laboratory accreditation: a Hong Kong perspective.
AB  - This is an account of the accreditation of the Surgical Pathology, Cytopathology,
      Autopsy Service, Haematology, Blood Bank, Bone Marrow Transplant and
      Electronmicroscopy Laboratories of the Department of Anatomical and Cellular
      Pathology, the Prince of Wales Hospital, Shatin, New Territories, Hong Kong, SAR,
      China, the first of their category to be accredited in the Special Administrative
      Region. The Australian-based National Association of Testing Authorities (NATA)
      used standards formulated by the National Pathology Accreditation Advisory
      Council (NPAAC) to measure the performance of the laboratory sections and to
      determine whether the laboratory service was of a sufficient standard to be
      granted accreditation. Some practices dating back to the colonial period required
      attention, while eliciting the support of staff at all levels was essential for
      achieving accreditation. Some cultural factors had to be taken into account when
      implementing changes. Finally, successful accreditation has provided the impetus
      for other Hong Kong laboratories to become accredited and this will have a
      beneficial flow-on effect for the entire region.

PMID- 12009094
TI  - Co-expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP
      receptor in cartilaginous tumours: a marker for malignancy?
AB  - AIM: Parathyroid hormone-related protein (PTHrP) is one of the critical factors
      for the differentiation and growth of chondrocytes. We examined the correlation
      between the co-expression of PTHrP and PTH/PTHrP receptor and the grade of
      malignancy in cartilaginous tumours. METHODS: We analysed PTHrP and PTH/PTHrP
      receptor expression in chondrosarcoma by immunohistochemistry and compared
      specific staining with the expression in benign cartilaginous tumours. There were
      38 cartilaginous bone tumours consisting of 26 chondrosarcoma, six enchondroma
      and six osteochondroma. Chondrosarcoma were composed of 20 conventional
      chondrosarcoma (10 grade 1, seven grade 2, and three grade 3), two
      dedifferentiated chondrosarcoma, two clear cell chondrosarcoma, and two myxoid
      chondrosarcoma. We performed the standard peroxidase-labelled streptavidin-biotin
      detection method for immunohistochemistry using an antibody raised against PTHrP
      (1-14) and PTH/PTHrP receptor. The magnitude of receptor positivity of PTHrP and
      PTH/ PTHrP in each tumour was assessed as a percentage of PTHrP and PTH/PTHrP
      positive cells per thousand tumour cells in the most histologically aggressive
      area of the tumour. RESULTS: All chondrosarcoma, five of six enchondroma, and
      four of six osteochondroma showed PTHrP-positive cells, and all chondrosarcoma,
      five of six enchondroma and five of six osteochondroma showed PTHrP receptor
      positive cells. The grade of malignancy correlated with the percentage of both
      PTHrP and PTH/PTHrP receptor-positive tumour cells (P < 0.0001, either). Each
      grade of chondrosarcoma showed statistically higher expression of both PTHrP and
      PTH/PTHrP receptor than benign cartilaginous tumour. CONCLUSION: This is the
      first report of the co-expression of PTHrP and PTH/PTHrP receptor in
      chondrosarcoma. PTHrP and PTH/PTHrP receptor positivity may be valuable for
      differentiating between benign and malignant cartilaginous tumours.

PMID- 12009095
TI  - Membranoproliferative glomerulonephritis in association with chronic lymphocytic
      leukaemia: a report of three cases.
AB  - AIMS: The reported association of glomerular disease with chronic lymphocytic
      leukaemia (CLL) is rare despite the relative frequency of this type of leukaemia.
      Hence, we have examined the renal biopsies in three patients with CLL and
      glomerulonephritis. METHODS: Renal biopsies were examined by light microscopy,
      immunofluorescence microscopy and electron microscopy. RESULTS: One of two
      patients with mild impairment of renal function and an active urinary sediment
      had ultrastructural features of idiopathic type I membranoproliferative
      glomerulonephritis (MPGN), and the other had features of fibrillary/
      immunotactoid glomerulonephritis with deposits of IgG and C3. One patient with
      nephrotic syndrome had characteristic electron microscopic appearances of type
      III MPGN. In all three there was an association with monoclonal gammopathy. The
      parameters of glomerular damage improved in association with response to drug
      treatment of the CLL. CONCLUSION: There is a spectrum of types of MPGN seen in
      patients with CLL and there appears to be an association with the presence of
      monoclonal gammopathy. This is the first reported case of type III MPGN in CLL.

PMID- 12009096
TI  - Rectosigmoid (colonic) xanthoma: a report of four cases and review of the
      literature.
AB  - AIM: Xanthomas of the colon appear to be rare lesions. Four cases are reported to
      bring wider attention to this entity. METHOD: Slides, reports and clinical notes
      from all cases coded as colonic or rectal xanthoma or xanthelasma during the
      period 1 January 1993 to 1 January 2000 were reviewed. The clinicopathological
      features are described and integrated into a review of nine previously reported
      cases. RESULTS: The ages of the patients ranged from 51 to 62 years (2M, 2F).
      Three lesions were located in the sigmoid colon and one in the rectum. They were
      all incidental findings at colonoscopy. Grossly, they varied from cream to yellow
      papules/polyps, ranged in size from 1 to 4mm and were all solitary. Two patients
      had an associated rectosigmoid hyperplastic polyp. There were no associated
      cutaneous xanthomatous lesions. One patient was diabetic and the serum lipid
      levels were normal in all patients. Histologically, all cases consisted of
      aggregates of mucosal foamy macrophages but in one case there were also
      macrophages involving the muscularis mucosae. The macrophages were negative for
      mucin and cytokeratin but were positive for CD68. CONCLUSION: Colonic xanthomas
      do not appear to be the cause of lower gastrointestinal symptoms and are an
      incidental colonoscopic finding as well as at times being seen in association
      with colonic polyps.

PMID- 12009097
TI  - Serous oligocystic adenoma of the pancreas: a clinicopathological and
      immunohistochemical study of three cases with ultrastructural findings.
AB  - AIMS: Serous oligocystic adenoma of the pancreas is an uncommon benign neoplasm
      and is a recently described entity. To date, there are 19 adult cases of this
      tumour. We report three additional cases, two with macrocystic and one with
      unilocular types. We describe their clinicopathological, immunohistochemical and
      ultrastructural findings and review the world's literature. METHODS: For a 10
      year period, we reviewed all benign cystic lesions of the pancreas with emphasis
      on serous oligocystic adenoma. We characterised serous oligocystic adenoma as an
      ill-demarcated or encapsulated mass, composed largely or exclusively of
      macrocysts (cysts measuring 20mm or more) but few in number (oligolocular).
      Grossly, it may contain only a single cyst (unilocular) of any size with a few
      satellite cysts observed on histological examination. Special stains and
      immunohistochemistry as well as electron microscopy were performed on three and
      two cases of serous oligocystic adenoma, respectively. RESULTS: Between 1990 and
      2000, we collected 26 benign cystic lesions of the pancreas, three of which were
      serous oligocystic adenomas (two with macrocystic and one with unilocular types).
      Many of the cells lining the cysts showed PAS positivity. There was negative
      staining for PAS with diastase digestion, Alcian blue and mucicarmine. All cases
      showed positive staining for CAM5.2, AE1/AE3, EMA and CK7. The proliferation
      index marker was low. There was negative staining for CK20, insulin, glucagon,
      somatostatin, synaptophysin, chromogranin A, CEA and p53. Ultrastructural studies
      on two cases revealed similar findings. The single row of uniform epithelial
      cells lining the cysts was composed of simple cuboidal to flat cells which rested
      on a thin basal lamina. Their nuclei were round to ovoid. Glycogen granules were
      identified in the cytoplasm. Short microvilli emerged from the epithelial apical
      surface. Adjacent tumour cells were connected by microfilaments. CONCLUSIONS:
      Serous oligocystic adenomas of the pancreas are uncommon benign tumours. Prior to
      this study, 19 adults with these lesions were reported in the world's literature.
      No correct pre-operative diagnosis was carried out on all 22 cases. The 20
      patients with follow-up ranging from 2 months to 5 years did not show tumour
      recurrence or malignant transformation.

PMID- 12009098
TI  - Investigation of coagulopathy in three cases of tiger snake (Notechis ater
      occidentalis) envenomation.
AB  - AIMS: To investigate the severe coagulopathy (fibrinogen < 1.0 g/l) that occurs
      in some cases of tiger snake envenomation. Specifically, to determine the
      concentration of clotting factors on presentation and during resolution of the
      coagulopathy. METHODS: Clotting factors II, V, VII, VIII, IX, XI were assayed on
      all coagulation samples received from three successive cases of severe tiger
      snake envenomations. Assays were performed at dilutions of 1:5 and 1:10 using an
      MLA 1600c automated coagulation analyser and Dade Behring factor-deficient
      plasmas, controls and standards. D-dimers were assayed using Agen Dimertest latex
      kit, fibrinogen was determined using the Clauss method and platelet counts were
      performed using Abbott Cell-Dyn 4000 analysers. RESULTS: The activity of the
      coagulation factors of the intrinsic pathway was reduced (factor VIII < 44% in
      all cases, factor IX < 33%, factor XI < 52% in Cases 1 and 2) but the results for
      the two dilutions were not parallel. In one case, factor VIII and factor IX
      activity increased 2-fold prior to the administration of blood products.
      Treatment with blood products corrected the coagulation indices in two out of the
      three cases but factor V remained low in one case (25%). CONCLUSIONS: The non
      parallel results and the apparent increase in factor levels prior to treatment
      may result from the transient presence of an inhibitor to factors VIII, IX and XI
      in cases of tiger snake envenomation. Insight into the effects of snake venom on
      individual coagulation factors could be beneficial when considering new
      treatments for the coagulopathy induced by snake envenomation.

PMID- 12009099
TI  - Prothrombin activation in eastern tiger snake bite.
AB  - AIMS: To perform ex vivo studies in eastern tiger snake envenomation which define
      the haemostatic events associated with prothrombin activation. METHOD: Serial
      studies were performed on plasma from six individuals with evidence of eastern
      tiger snake envenomation. These analyses were particularly directed to fibrinogen
      levels, F1 + 2, TAT and evidence of fibrinolysis. RESULTS: There was a
      substantial rise in F1 + 2 and thrombin-antithrombin (TAT) complexes in all
      cases, even with minimal evenomation. In some cases the molar ratio of F1 + 2 and
      TAT was reduced from the relationship normally seen in vitro and ex vivo in
      clinical thrombosis. There was a dramatic fall in factor V and VIII levels which
      occurred 4-6 hours before the decline in prothrombin and AT3. This related in
      time to a fall in alpha2AP and plasminogen. Protein C levels also declined
      dramatically but many hours after presentation. CONCLUSIONS: F1 + 2 and TAT are
      sensitive markers of tiger snake evenomation. In some patients with massive
      prothrombin activation, the common mechanism for TAT clearance may be altered or
      overwhelmed. Conversely, the renal clearance of the smaller F1 + 2 may be
      enhanced. In the absence of thrombocytopaenia, which is a very sensitive marker
      of DIC, the fall in labile factors with tiger snake envenomation is significantly
      contributed to by proteolytic digestion of clotting factors.

PMID- 12009100
TI  - Determination of the optimum incubation period of continuously monitored blood
      cultures from patients with suspected endocarditis or fungaemia.
AB  - AIM: It is routine practice to prolong the incubation period of blood cultures
      from patients with suspected subacute bacterial endocarditis (SBE) or fungal
      infection. The protocol in this laboratory required 28 days incubation with
      weekly subcultures. Following the introduction of automated continuously
      monitored blood culture instruments, the duration of incubation for specimens
      from these categories of patients was reviewed. METHOD: In a retrospective study
      of blood culture specimens submitted from 1 July 1994 to 31 July 1998, the time
      from collection to a positive signal from the BacT/Alert automated blood culture
      system, in patients suspected of SBE or fungal infection, was assessed. RESULTS:
      From 355 patient episodes, 896 bottles were incubated for up to 28 days, during
      which time 116 bottles (40 patient episodes) signalled positive. Significant
      organisms from suspected endocarditis patients were isolated from 87 bottles
      (87%), with the time to detection ranging from 9 to 96 hours. The data collected
      from significant isolates obtained from clinically suspected fungaemias were
      extremely small, prompting a review of the total fungal isolates from all blood
      culture bottles incubated during the study period. Yeast isolates were obtained
      from 78 (0.08%) bottles with the detection time ranging from 15 to 144 hours.
      CONCLUSION: The practice in this laboratory now is to incubate blood cultures for
      up to 7 days when the clinical notes indicate the possibility of SBE or a fungal
      infection.

PMID- 12009101
TI  - Evaluation of an automated urinalysis system for testing urine chemistry,
      microscopy and culture.
AB  - AIMS: This study was designed to evaluate the performance of an automated
      urinalysis system that utilised three commercially available instruments, the
      Clinitek Atlas, Sysmex UF-100 and the Alifax Uro-Quick. METHODS: The results of
      the automated system for 818 urine samples were compared with the results of
      manual processing which consisted of phase contrast microscopy, manual dipstick
      chemistry analysis and culture onto solid media. RESULTS: The correlation between
      the two methods for urine chemistry was excellent with a concordance of 89, 97,
      100 and 98% for pH, blood, glucose and protein, respectively. The quantification
      of red blood cells and white blood cells had an R2 of 0.855 and 0.92,
      respectively. A difference scatter plot indicated a trend towards the manual cell
      count being greater than the UF-100 count as both the red and white blood cell
      count increased. There was 98% agreement between the automated process and manual
      culture. CONCLUSIONS: The automated urinalysis system is fully integrated and
      allows for the cross-checking of urine chemistry and microscopy as well as
      electronic transfer of data. The automated process was used as a screening
      procedure and some manual testing was necessary. Automation of urinalysis offers
      a reduction in variation and has comparable results to manual testing.

PMID- 12009102
TI  - Limiting potential infectious risks of transplanting insulin-producing pig cells
      into humans.
AB  - AIMS: Prior to commencing a study of grafting foetal/neonatal pig islet-like cell
      clusters into type I diabetic human subjects, the microbiological risks of
      transplanting porcine pancreatic tissue were assessed. METHODS: An exclusion list
      for screening donor animals and graft tissue in Australia was compiled following
      evaluation of the disease risks posed by 121 organisms, including 36 bacteria, 12
      fungi, four mycoplasma, 31 parasites and 38 viruses. The list of evaluated agents
      was derived from the literature, interviews with veterinarians and physicians,
      and a survey of laboratories. RESULTS: The exclusion list contains 35 organisms
      (including 20 bacteria, four fungi, one mycoplasma, one parasite and nine
      viruses) that are zoonotic, pathogens of immunocompromised hosts (including human
      allograft recipients), pathogens resistant to antibiotics or potentially able to
      recombine with the human genome. These 35 agents can be detected by culture
      (e.g., Actinomyces), serological testing (e.g., influenza viruses) or nucleic
      acid amplification (e.g., Mycobacteria). CONCLUSIONS: It is recommended that: (i)
      source pigs designated for use in human xenotransplantation trials should be
      tested regularly for the 35 organisms; (ii) the mothers of donor foetal/neonatal
      pigs and, when possible, the foetal/ neonatal pigs themselves should be tested
      immediately prior to the grafting of tissue into humans; and (iii) the exclusion
      list be modified for designated source pig herds in countries other than
      Australia.

PMID- 12009103
TI  - An intraventricular brain tumour in a young woman. Part 1. Central neurocytoma.

PMID- 12009104
TI  - Solitary fibrous tumour in the deep soft tissue of the neck in a Chinese man.
AB  - Originally described in the pleura, solitary fibrous tumour (SFT) is now reported
      in a variety of extrapleural sites. However, description of SFT in the deep soft
      tissue of the neck is very rare. In this report, we document the neoplasm, deep
      to the right platsyma muscle but superficial to the deep fascia just above the
      clavicle, in an otherwise well 50-year-old Chinese man. Histological examination
      of the excised specimen disclosed spindle-shaped cells disposed in short
      fascicles as well as randomly in association with areas of varying cellularity,
      keloidal hyalinisation of the stroma and haemangiopericytoma-like vessels. The
      tumour cells were CD34-, bcl-2- and CD99-positive. Since histological features
      may not accurately predict the biological behaviour of this tumour, careful long
      term follow-up is advocated.

PMID- 12009105
TI  - Glomangiomyoma (glomus tumour) of the pancreas: a case report.
AB  - Glomus tumours occur in many sites. We report the first case of a glomangiomyoma
      in the pancreas of a 17-year-old girl. The tumour was 5cm in diameter and
      consisted of rounded glomus cells, blood vessels and spindled smooth muscle
      cells. The glomus and smooth muscle tumour cells showed moderate diffuse
      cytoplasmic staining with vimentin, muscle-specific actin and smooth muscle
      actin. There was weak focal positivity for desmin in the spindle cell component
      only. The patient is alive and well with no evidence of recurrence 24 months
      after surgery.

PMID- 12009106
TI  - Trichilemmoma and syringocystadenoma papilliferum arising in naevus sebaceous.

PMID- 12009107
TI  - Sarcomatoid squamous cell carcinoma of the vulva.

PMID- 12009108
TI  - Fibrocartilaginous mesenchymoma arising in the femur.

PMID- 12009109
TI  - Mobile phones and your health.

PMID- 12009110
TI  - Toxicities of two freshwater puffers in Taiwan.
AB  - Forty-two and twelve specimens of puffers Tetraodon ocellatus and T. nigroviridis
      were, respectively, collected from the aquaria in Taiwan and determined for
      toxicity by using tetrodotoxin bioassay. It was found that T. ocellatus contained
      moderate amounts of toxin in skin and viscera, and the highest toxicity scores
      were 432 MU/g skin and 212 MU/g viscera. The specimens of T. nigroviridus
      contained weak amounts of toxin in skin, and the highest toxicity score was 124
      MU/g. The toxin was partially purified from the toxic specimens of each species
      by ultrafiltration using a YM-1 membrane, followed by chromatography on Bio-Gel P
      2 column. Analyses by electrophoresis, thin layer chromatography, and high
      performance liquid chromatography showed that the toxin from both species was
      composed of tetrodotoxin and anhydrotetrodotoxin.

PMID- 12009111
TI  - Renal function following sea snake venom (Lapemis hardwicki) administration in
      dogs treated with sodium bicarbonate solution.
AB  - The effects of sea snake venom (SSV) on renal function were studied in two groups
      of anesthetized experimental dogs pretreated with intravenous infusion of 4.2 gm%
      NaHCO3 solution. Animals were envenomated by intramuscular injection of SSV at a
      dosage of 0.34 mg/kg. Systemic hemodynamics showed no significant changes except
      for a tendency of decrease in cardiac output (CO). The glomerular filtration rate
      (GFR), the rate of urine flow (V) and effective renal plasma flow (ERPF), and
      effective renal blood flow (ERBF) significantly decreased, while filtration
      fraction (FF) significantly increased at 180 min after envenomation. Envenomated
      animals showed a reduction in renal fraction (RF), while renal vascular
      resistance (RVR) increased stepwise throughout the experimental periods. Animals
      pretreated with sodium bicarbonate showed no significant changes of CO, TPR MAP,
      HR, and packed cell volume (PCV) while receiving sea snake venom. Animals
      pretreated with sodium bicarbonate showed no changes in GFR, ERPF, ERBF, RF, and
      RVR after envenomation. The rate of urine flow markedly increased in envenomated
      animals which received pretreatment with bicarbonate. After envenomation alone,
      there were no differences in the plasma concentration of sodium (PNa) and
      chloride (PCl) as compared to the control value, whereas the plasma concentration
      of potassium (PK) increased at 180 min after envenomation. Animals pre-treated
      with bicarbonate showed a stepwise increase in both UNaV, FE(NA), U(Cl)V, and
      FE(Cl) accompanying SSV injection. Neither PNa nor PCl were affected, while PK
      significantly decreased in animals given SSV with bicarbonate loading. UKV and
      FEK increased stepwise in envenomated animals treated with bicarbonate throughout
      the period of study. All groups of animals given SSV, with or without NaHCO3
      infusion, showed a marked elevation of the concentration of urinary myoglobin
      (U(Mb)), plasma lactate dehydrogenase (LDH), and plasma creatine phosphokinase
      (CPK) throughout experimental periods. The urinary myoglobin excretion markedly
      increased in animals after SSV injection accompanied by NaHCO3 infusion. It can
      be concluded that large amounts of myoglobin present in the renal tubules in
      envenomated animals can precipitate, particularly under acidic conditions,
      resulting in increased intratubular pressure and subsequently decreased renal
      hemodynamics including GFR and ERBF. An infusion of NaHCO3 to render urine more
      alkaline could have a protective role against depression of renal function
      following sea snake venom administration.

PMID- 12009112
TI  - Development of an improved method for production of antiscorpion F(ab')2 fragment
      of IgG with high yield and potency.
AB  - The main objective of the present work was to obtain a stable and highly purified
      scorpion antitixon, rich in specific antibodies, free of immunologically
      irrelevant plasma proteins or gross proteins. Our results indicate that the most
      potent yielded and purified F(ab')2 antivenom preparation was obtained when the
      first discarded precipitate was washed with 14% ammonium sulphate saline; then
      after the second addition of ammonium sulphate, the mixture was stirring
      overnight followed by precipitation of most non-immunoglobulin proteins with the
      aid of caprylic acid to produce antivenom rich in specific antibodies with higher
      yield and potency compared to the method commonly used.

PMID- 12009113
TI  - Aflatoxin in detannin coffee and tea and its destruction.
AB  - The aflatoxins produced byAspergillus parasiticus var. globosus IMI 12090 in
      detannin-caffeinated coffee and black tea were five times more concentrated than
      in regular coffee and tea. The activity of caffeine and tannin on the fungus
      growth and aflatoxin production in liquid broth was tested at three levels: viz.
      0.1, 0.3, and 0.6%. Tannin and caffeine induced 95% inhibition in aflatoxins at
      0.3% and 0.6%, respectively. The antiaflatoxigenic properties of regular coffee
      and tea appear to be due to tannin, followed by caffeine. The roasting of
      contaminated coffee beans at 200 degrees C for 20 min is effective in the
      destruction of aflatoxins.

PMID- 12009114
TI  - Primary structure and pathological study of phospholipase A2-I from Agkistrodon
      bilineatus (common cantil) venom.
AB  - Phospholipase A2-I (PLA2-I) was isolated from Agkistrodon bilineatus venom by
      Nikai (Nikai et al., 1993). The amino acid sequence of the phospholipase A2-I was
      determined by the Edman sequencing procedure of peptides derived from digests
      utilizing cyanogen bromide, clostripain, metalloendopeptidase, chymotrypsin, and
      Staphylococcus aureus V8 protease. In the reduced state, purified phospholipase
      A2's molecular weight was determined to be 14,000 as demonstrated by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis. Purified PLA2-I also contained
      1 mol of Ca per mol of protein and consists of 123 amino acid residues resulting
      in a calculated molecular weight of 14,133. Both phospholipase and lethal
      activities were found to be inhibited by bromophenacyl bromide, suggesting that
      the histidine residue is involved in this activity. Also there was an increase in
      the creatine kinase activity of mice serum, which is an indicator that PLA2-I is
      involved in muscle damage.

PMID- 12009115
TI  - Pardaxin, an ionophore neurotoxin, induces PC12 cell death: activation of stress
      kinases and production of reactive oxygen species.
AB  - Pardaxin (PX) is an ionophore neurotoxin that induces neurotransmitter release at
      subcytotoxic concentrations and causes necrotic cell death at higher
      concentrations. Since cell survival, physiological processes, and cell death are
      under the control of signaling pathways converging to MAPKs (ERK, JNK, and p38
      isoenzymes), we determined the interaction of PX with these enzymes. We report
      that PX (5 microM) transiently stimulated MAPKs. While the activation of ERKs was
      rapid (min), the stimulation of JNK and p38 was delayed (hr). At toxic
      concentrations of PX ( < 20 microM) the activation of JNK and p38 was fast and a
      sharp increase in radical oxygen species (ROS) was measured before cell
      disintegration was observed. PX (5 microM) also induced dopamine release without
      significant leakage of lactate dehydrogenase (LDH), indicating a physiological
      effect in the absence of cytotoxicity. On the basis of these findings, we propose
      a model in which there is a balanced relationship between PX stimulation of MAPKs
      and the physiological/pathological effects of this toxin. Although under
      physiological conditions ERKs activation is responsible for the regulation of
      survival-related processes, under pathological conditions JNK and p38 are
      stimulated, most probably in correlation to cell death. The fine correlation
      between these kinases is likely disturbed by PX and remains to be further
      investigated.

PMID- 12009116
TI  - Restoration of nerve growth factor in organs of mice injected with cobra venom
      followed by specific treatment and reversal period.
AB  - Research from this laboratory reported the decreased levels of endogenously
      present nerve growth factor (NGF) in organs of mice as a consequence of sub
      lethal injection of Naja kaouthia venom. This research reports that the decreased
      levels of NGF in organs of mice were prevented by (1) specific treatment and (2)
      restored to normal by a prolonged period. Adult female Balb/c mice were injected
      intramuscularly (IM) with a sub-lethal dose of cobra venom. The injected mice
      were divided into five groups. Mice in group I were injected with PBS, group II
      with anti-cobra venom, and group III with lethal toxin neutralizing factor
      (LTNF). Mice in group IV were treated IM with synthetic LTNF (LT-10), and mice in
      group V were treated orally with LT-10. After 24 hr. mice were sacrificed and NGF
      levels in organ homogenates were assayed and compared with control mice not
      injected with venom. It was observed that the organs from group I treated with
      PBS showed a tremendous drop in NGF level in comparison to the organs of the
      control mice. It was further revealed that the decreased levels of NGF in organs
      of injected mice were prevented by treatment with anti-cobra venom, LTNF and LT
      10 by IM, or oral routes. In the second series of experiments, mice injected with
      sub-lethal dose of cobra venom were sacrificed after 1, 3, 7, and 10 days, and
      the organs were assayed for NGF levels. It was observed that the recovery period
      for normal homeostasis of NGF was between 7 and 10 days in the brain, heart,
      liver, salivary glands, and ovaries.

PMID- 12009117
TI  - Cloning, expression, and biological activity of recombinant alpha-cinnamomin:
      toxicity to cranberry and other plant species.
AB  - Elicitins produced by the pathogenic fungi Phytophthora are known to exhibit The
      elicitin cinnamomin is of nonspecific toxicity to different solanaceous plant
      species. particular interest for its potential role in the hypersensitive-like
      cell death and in the biological response of cranberry plants to the fungal
      pathogen Phytophthora cinnamomi. In order to understand the biochemical steps of
      the Phytophthora root rot disease in cranberry, we investigated the alpha
      cinnamomin-induced plant responses. Toxicity of alpha-cinnamomin, which shows a
      high degree of sequence homology to the alpha-elicitin group, was tested on
      Vaccinum macrocarpon, Nicotiana tabacum, Capsicum annuum, Lycopersicon
      esculentum, Lactuca sativa, and Phaseolus vulgaris plants. Gene corresponding to
      alpha-cinnamomin gene fused with maltose binding protein gene, was cloned into a
      pMALTEV expression vector, which was transformed into E. coli cells. Cells
      containing alpha-cinnamomin clones were cultured and extracted protein was
      purified on a maltose binding protein affinity column. Biological activity of
      alpha-cinnamomin fusion protein was examined on propagated plants and cuttings.
      In cranberry plants treated with cinnamomin necrotic hypersensitive-like response
      in the proximal areas of the leaf lamina of lower plant leaves was observed after
      48-72 hr of incubation. Limited leaf necrosis observed days after application of
      low amounts of recombinant cinnamomin directly on the leaves of other plants
      indicates that the recombinant protein might be functioning as a toxin, capable
      of inducing aging accompanied by plant cell death.

PMID- 12009118
TI  - Evaluation of ergonomic adjustments of catering carts to reduce external pushing
      forces.
AB  - An existing standard catering cart was compared with two prototypes for pushbar
      and castor design. The first objective of this study was to find out which cart
      was accompanied with the lowest manually exerted external forces in pushing in a
      straight way and in pushing a 90 turn. The second objective was to explore
      effects of the pushbar and castor design of the carts. In the initial and ending
      phase, the prototypes were accompanied with higher exerted forces compared with
      the standard catering cart. In pushing straight. the reversed start position of
      the bigger castors of the prototypes hampered a fluent acceleration and caused
      higher initial forces. In decelerating, the lower rolling friction of the bigger
      castors required higher forces to stop the prototypes compared to the standard
      cart. During the sustained phase, the prototype carts were more favourable.
      Effects of pushbar and castor design were studied during a turn. The vertical
      pushbars of the prototypes resulted in lower time-integrated pushing forces.
      Providing an axis of rotation for turning activities by means of a fixed wheel
      was proven to be advantageous.

PMID- 12009119
TI  - Short term and long term effects of enhanced auditory feedback on typing force,
      EMG, and comfort while typing.
AB  - Two studies were conducted to determine the effects of enhanced auditory feedback
      on typing force, electromyography (EMG) and subjective discomfort. The
      introduction of enhanced auditory feedback caused a 10-20% reduction in 90th
      percentile typing force, finger flexor EMG, and finger extensor EMG. Adaptation
      to the enhanced auditory feedback occurred in <3 min. After 1 week of
      intermittent enhanced auditory feedback there were no differences in typing force
      or EMG while subjects were typing with or without the enhanced auditory feedback.
      The continued use of auditory feedback did not further reduce the levels of
      typing force or EMG after 1 or 2 weeks of exposure.

PMID- 12009120
TI  - Tractor-driving hours and their relation to self-reported low-back and hip
      symptoms.
AB  - Tractor driving might be one causal risk factor in the incidence of low-back and
      hip symptoms among farmers. Information on the annual exposure to tractor driving
      and its distribution among different work operations is scarce. The purpose of
      this study was to quantify the total and the annual time driving tractors among
      Swedish farmers and its distribution into different work operations, and to
      investigate the risk of low-back and hip symptoms in relation to tractor driving
      within different work operations. The data were collected from a questionnaire
      study sent to all farms with acreage more than 10 ha in a county in Sweden.
      Farmers having farming and/or forestry as their main occupation in 1995 were
      included in the analysis. The annual tractor-driving time and the percentage
      distribution within different work operations were calculated for females, males,
      the total group and four production groups. The risk calculations for low-back
      and hip symptoms from the variables related to tractor driving were performed on
      the total group. The results showed that the mean annual tractor-driving time was
      472 h. Ploughing was the single most time-consuming work operation but it had no
      influence on the risk for low-back or hip pain. The results showed that some of
      the variables investigated related to tractor driving influenced the risk for low
      back and hip symptoms.

PMID- 12009121
TI  - Computer-telephone interactive tasks: predictors of musculoskeletal disorders
      according to work analysis and workers' perception.
AB  - Sixty-two workers engaged in computer-telephone interactive tasks in an active
      telemarketing center and a telephone call center of an international bank
      subsidiary in Sao Paulo. Brazil, were assessed by means of a work analysis and a
      self-administered questionnaire aiming to determine the statistical relationship
      of ergonomic, organizational and psychosocial characteristics of their jobs with
      the report of symptoms in neck-shoulder and hand-wrist for more than 7
      consecutive days and any time away from work during the current job due to
      musculoskeletal disorders (MSD). According to chi-square univariate tests and
      multiple logistic regression models, active telemarketing operations, duration in
      the job and the low level of satisfaction with the physical arrangement of the
      workstation emerged as the factors most related to neck-shoulder and hand-wrist
      MSD and MSD-induced time away from work. This study emphasizes the role of
      psychosocial factors and duration in the job in MSD occurrence and induced
      absenteeism among workers engaged in computer-telephone interactive tasks.

PMID- 12009122
TI  - Analysis of interaction quality in human-machine systems: applications for
      forklifts.
AB  - The aim of the work presented here was to propose a methodology for analysis of
      interactions between humans and machines. The driver-truck system in a warehouse
      context was used as a case for empirical evaluation. The work consists of three
      empirical studies and one analysis of statistical data. In total 29 pallet truck
      drivers have been involved in the studies which were performed at two Swedish
      distribution companies. A framework is proposed, where effects on performance,
      safety, subjective experiences and physical and mental impact on the humans are
      used as indicators of the quality of interactions. The results show that the
      methodology proposed supports appropriate input for the evaluation of the
      interaction quality between humans and technology. One example of this is
      musculoskeletal loads and discomfort, which could be related to the task and the
      design of the steering arm. Another conclusion from this work is that many
      factors outside the warehouse truck affect the interaction in the human-truck
      system, for example the design of loading ramps. This supports the importance of
      having a holistic ergonomics view when studying a human-machine system.

PMID- 12009123
TI  - The effect of different surfaces on biomechanical loading of shoulder and lumbar
      spine during pushing and pulling of two-wheeled containers.
AB  - Seven waste collectors pushed and pulled a two-wheeled container on three
      different surfaces: flagstones, paving stones, grass. Net torques at the shoulder
      joint and the lumbar spine as well as the compression and shear forces in the
      lumbar spine at the L4/L5 level were calculated for the tilting, initial and
      sustained phases. The lumbar spine compression force was below 1800N and the
      shear force was below 200 N in all situations. The shoulder torque when pulling
      with one hand was up to 80 N m. The container weight affected the magnitude of
      the push/pull forces and the load on the shoulders but not the load on the lumbar
      spine. The type of surface affected the magnitude of the push/pull forces during
      initial and sustained phases, and affected the load on the shoulder in the
      sustained phase. However, it did not affect the compression in the lumbar spine.

PMID- 12009124
TI  - An investigation of ergonomic interventions in dental hygiene work.
AB  - Alternative methods for viewing teeth while performing simulated dental
      procedures were investigated. The methods allowed participants to assume postures
      requiring less neck flexion than the standard direct view. One alternative used a
      video camera and monitor to view the mouth, the other incorporated 90 degrees
      prism glasses. The study was conducted in two parts: (1) novice participants
      performing a targeting task; (2) dental hygienists performing a scaling task on a
      mouth model. Posture and subjective perceptions were assessed in Parts 1 and 2.
      Muscle activity and performance were also assessed in Part 1. The alternative
      methods significantly reduced muscle activity, neck flexion, and discomfort,
      compared to the direct view. Preferences were a function of criteria (general,
      comfort, productivity, or accuracy). Previously, recommendations for reducing
      ergonomic risk factor exposure of dental professionals emphasized reducing time
      spent performing dental procedures. This study shows ergonomic interventions
      offer alternative means of risk exposure reduction.

PMID- 12009125
TI  - A simple and fast screening test to detect soils polluted by lead.
AB  - Lead pollution is an environmental priority. The evaluation of contaminated soils
      was often based on the results of the toxicity characteristic leaching procedure
      (TCLP) or the synthetic precipitation leaching procedure (SPLP). This paper
      presents a simple and fast screening test to detect soil contaminated by lead.
      The test is based on the chemistry of the stomach (Cl- concentration, pH 2, T =
      37 degrees C) and simulates the incidental oral ingestion of soil by young
      children. The gastric juice simulation test (GJST) and the TCLP were applied to
      six size fractions from five soils. The GJST solubilized more Pb (up to 169 mg/l)
      than the TCLP especially for the smallest size fraction. Particle size had less
      effect on the TCLP. The percentage of lead released with the GJST, was most
      significant for the <63 microm size fraction and varied from 18 to 74% of the
      total lead content. Lead leached during the TCLP as a function of the total lead
      content showed poor linear regression coefficient (R) values for soils <250
      microm. R values were significant for all size fractions with the GJST. The pH of
      approximately 5 in the TCLP limits the solubilization of lead in the small size
      fractions. The five soils exceeded the toxicity threshold of 10 microgPb/dl of
      blood for a significant fraction of children between 0 and 36 months using the
      EPA's IEUBK model (Integrated Exposure Uptake Biokinetic). But the TCLP did not
      detect lead contamination in two of these five soils. The GJST proved to be a
      better estimator of lead bioaccessibility in the gastrointestinal tract.

PMID- 12009126
TI  - Effects of Cd and Zn waterborne exposure on the uptake and depuration of 57Co,
      110mAg and 134Cs by the Asiatic clam (Corbicula fluminea) and the zebra mussel
      (Dreissena polymorpha)--whole organism study.
AB  - Groups of zebra mussels (Dreissena polymorpha) and asiatic clams (Corbicula
      fluminea) were exposed to cadmium and zinc with the aim of studying the effect of
      these metals on the 57Co, 110Ag and 134Cs uptake and depuration by these
      freshwater bivalves. In the presence of zinc, the 57Co concentration factor for
      the whole organism of the two species was halved, notably because of a decrease
      of the uptake parameter. Conversely, Zinc and the Cd + Zn mixture increased the
      110mAg uptake process by clams and mussels. The two metals also increased the
      depuration of this radionuclide in mussels, whereas this phenomenon was only
      observed in clams exposed to cadmium. In comparison with 57Co and 110mAg, the
      134Cs bioconcentration was 5-10 times lower in D. polymorpha and not detected in
      C. fluminea. This weak contamination by this radionuclide resulted from a lower
      uptake and a higher depuration parameters.

PMID- 12009127
TI  - Solubilization of PAH mixtures by three different anionic surfactants.
AB  - Solubilization of naphthalene and phenanthrene into the micelles formed by three
      different anionic surfactants was investigated for single, binary, and ternary
      mixtures including pyrene. The three surfactants were sodium dodecylbenzene
      sulfonate (SDDBS), monoalkylated disulfonated diphenyl oxide (MADS-C12), and
      dialkylated disulfonated diphenyl oxide (DADS-C12). The order of increasing
      solubility enhancement of naphthalene and phenanthrene was SDDBS < MADS-C12 < <
      DADS-C12, which indicates that the hydrophobic chains in micellar core play more
      important role for the solubilization of polycyclic aromatic hydrocarbons (PAHs)
      than the benzene rings in palisade layer of a micelle. The solubility enhancement
      of naphthalene was slightly changed in PAH mixtures. The solubility of
      phenanthrene was greatly enhanced in presence of naphthalene but reduced in
      presence of pyrene. The explanation for these results could be that less
      hydrophobic compounds can be solubilized at the interfacial region of a
      hydrophobic core, which reduces the interfacial tension between the core and
      water, and then the reduced interfacial tension can support a larger core volume
      for the same interfacial energy.

PMID- 12009128
TI  - Adsorption of phenols by papermill sludges.
AB  - In this paper we studied the sorption capacity of paper mill sludges for phenols.
      Phenol, 2-chlorophenol (2-CP), 3-chlorophenol 3-CP). 4-chlorophenol (4-CP), 2
      nitrophenol (2-NP), 4-nitrophenol (4-NP), 2.4-dichlorophenol (2,4-DCP), 3,4
      dichlorophenol (3,4-DCP) 3,5-dichlorophenol (3,5-DCP) and 2,4,5-trichlorophenol
      (2,4,5-TCP) were chosen for the sorption tests. Kinetic experiments showed that
      substituted-phenol sorption on papermill sludge was rapid (equilibrium was
      reached after 3 h); conversely, the time taken by the phenol to reach equilibrium
      conditions was 260 h. Experimental data showed that particle diffusion was
      involved in the sorption process but was not the only rate-limiting mechanism;
      several other mechanisms were involved. The adsorption isotherms showed the
      following order of retention capacity of papermill sludge: 2-NP = 4-NP < < 2-CP <
      phenol < 4-CP < or = 3-CP < 2,4 DCP<3,4 DCP=2,4,5 TCP<3,5 DCP. In all cases the
      experimental data showed a good fit with the Hill equation. which is
      mathemratically equivalent to the Langmuir-Freundlich model obtained by assuming
      that the surface is homogeneous, and that the adsorption is a cooperative process
      influenced by adsorbate-adsorbate interactions.

PMID- 12009129
TI  - Early reproductive success of western bluebirds and ash-throated flycatchers: a
      landscape-contaminant perspective.
AB  - Eggshell quality, clutch size, sex ratio, and hatching success of western
      bluebirds (Sialia mexicana) and ash-throated flycatchers (Myiarchus cinerascens)
      were studied on a landscape-soil contaminant gradient at Los Alamos National
      Laboratory (LANL) in New Mexico from 1997 to 1999. A variety of contaminants
      (heavy metals, chemicals, insecticides, polychlorinated biphenyls (PCBs),
      organochlorines, and radioactive isotopes) range across different spatial scales
      and concentrations on LANL land. This study is an example of a monitoring program
      over a large area with varying degree of contamination that is used to highlight
      locations of concern for future research. There were two locations where the
      flycatcher had a lower hatching success. The bluebirds at Sandia wetland, a
      location of concern for PCBs. had a thinner eggshell thickness index (RATCLIFFE)
      and the eggs were smaller than at other locations. The flycatcher had thinner
      eggshells than bluebirds, which could add to sensitivity to exposure to
      contaminants. There was no variation in clutch size or sex ratio between
      locations or areas closer to contaminant release sites for both species. Percent
      females in the clutch ranged from 0 to 100% in the WEBL and from 33 to 67% for
      ATFL.

PMID- 12009130
TI  - Water quality at five marinas in Lake Texoma as related to methyl tert-butyl
      ether (MTBE).
AB  - Water quality in five marinas on Lake Texoma, located on the Oklahoma and Texas
      border, was monitored between June 1999 and November 2000. Focus was to evaluate
      lake water associated with marinas for methyl tert-butyl ether (MTBE). Lake water
      was collected at locations identified as marina entrance, gasoline filling
      station, and boat dock. Occurrence of MTBE showed a direct seasonal trend with
      recreational boating activity at marina areas. There was a positive correlation
      with powerboat usage ratio, which was directly related to the gallons of gasoline
      sold. Sampling before and after the high boat use holiday weekends determined the
      apparent influence of powerboat activity on MTBE contamination. Boat dock
      locations were the most sensitive sites to MTBE contamination, possibly due to
      gasoline spillage during engine startup. The most common compound of the BTEX
      series found with MTBE was toluene and co-occurrence was most frequent at
      gasoline filling stations.

PMID- 12009131
TI  - Bioindicator reliability: the example of Bel W3 tobacco (Nicotiana tabacum L.).
AB  - The use of the Bel W3 tobacco variety revealed the existence of an
      intrapopulation variation of sensitivity to the ozone effect leading to the
      isolation of two categories of plants: sensitive and resistant. The use of
      sensitive plants revealed the existence of a biological ozone efficiency
      threshold at a level close to 34.5 ppb. Under the threshold, the biological
      effects observed were weak or very weak. They can be attributed to the occurrence
      of secondary phenomena (chemical, physiological, pathological, etc.), inducing or
      inhibiting necrosis, which become perceptible here.

PMID- 12009132
TI  - Tolerance to, and avoidance of, hypoxia by the penaeid shrimp (Metapenaeus
      ensis).
AB  - Aquatic hypoxia caused by eutrophication may lead to mass mortality of valuable
      living resources such as fish and shrimp. However, there is little information on
      the hypoxic tolerance of penaeid shrimp, and whether they are able to avoid
      hypoxia. In laboratory experiments, LC50, LT50 and heart beats per minute were
      determined for juvenile Metapenaeus ensis at 0.5, 1.0, 2.0 and 6.0 mg O2 l(-1).
      The 8-h LC50, for DO was 0.77 mg O2 l(-1), while the LT50 at 0.5 mg O2 l(-1) was
      399 min. Heart beat rate significantly declined when DO fell below 1.0 mg O2 l(
      1). When confronted with a gradient of dissolved oxygen, M. ensis were able to
      avoid hypoxic areas and move to oxygenated water. M. ensis appeared to be
      sensitive to hypoxia, and their ability to detect and avoid hypoxia may enhance
      their survival in habitats where hypoxia may occur.

PMID- 12009133
TI  - Reduction of perchlorate and nitrate by salt tolerant bacteria.
AB  - Spent regenerant brine from ion-exchange technology for the removal of
      perchlorate and nitrate produces a high salt waste stream, which requires
      remediation before disposal. Bioremediation is an attractive treatment option. In
      this study, we enriched for salt tolerant bacteria from sediments from Cargill
      salt evaporation facility (California, USA), the Salton Sea (California, USA),
      and a high density hydrocarbon oxidizing bacterial cocktail. The bacterial
      cocktail enrichment culture reduced ClO4- from 500 to 260 mg 1 in 4 weeks. Salt
      tolerant bacterial isolates from the enrichment cultures and two denitrifying
      salt tolerant bacteria, Haloferax denitrificans and Parococcus halodenitricans,
      substantially reduced perchlorate. The highest rate of perchlorate removal was
      recorded with the isolate, Citrobacter sp.: 32% reduction in 1 week. This
      bacterium substantially reduced perchlorate in 0-5% NaCl solutions and maximally
      at 30 degrees C and at an initial pH 7.5. In simulated brines containing 7.5%
      total solids, the Citrobacter sp. significantly reduced both perchlorate and
      nitrate with 34.9 and 15.6% reduction, respectively, in 1 week. Coculture of a
      potent perchlorate reducing, non-salt tolerant (non-saline) bacterium, perclace
      and the Citrobacter sp. proved most effective for perchlorate removal in the
      brine (46.4% in 1 week). This study demonstrates that both anions can be reduced
      in treatment of brines from ion exchange systems.

PMID- 12009134
TI  - Recent sedimentary history of anthropogenic impacts on the Culiacan River
      Estuary, northwestern Mexico: geochemical evidence from organic matter and
      nutrients.
AB  - 210Pb geochronology and sediment profiles of carbon, phosphorus and nitrogen were
      used to study time dependent changes in nutrients fluxes to Culiacan River
      Estuary. Results indicate that the release of urban sewage and agriculture wastes
      transported through Culiacan River has produced historically increased carbon,
      phosphorus and nitrogen fluxes to the study area. C:N:P elemental ratios showed
      that increments in the nutrients input begins simultaneously for C, N and P in
      1948 with the clearing of the catchment for agriculture; although excess of
      nutrients input increased most importantly around the 1970s to roughly follow the
      rapidly growing population of Culiacan City. C/N ratios, delta13C and delta15N
      suggested that nutrient enrichment is mostly influenced by sewage delivered
      through Culiacan River.

PMID- 12009135
TI  - Isolation and characterization of biarylic structure-degrading yeasts:
      hydroxylation potential of dibenzofuran.
AB  - Yeast communities from heavily polluted sediments that received the discharge
      from oil refineries and other industries were studied. Yeast species were
      isolated from these sediments and their ability to degrade dibenzofuran were
      determined. Twenty-four different yeast strains were isolated and cultured on
      aromatic medium; two Candida krusei strains. Candida tenuis, Candida tropicalis,
      two Pichia anomala strains, Pichia haplophila, two Rhodotorula glutinis strains,
      Rhodotorula mucilaginosa, two Trichosporon pullulans strains and Yarrowia
      lipolytica were able to hydroxylate dibenzofuran. Three metabolites were
      identified by HPLC analysis: 3-hydroxydibenzofuran was in all the cases the most
      abundant isomer, and while 4-hydroxydibenzofuran was also common, 2
      hydroxydibenzofuran was detected in very small quantities and with few species.
      In the R. glutinis and Y. lipolytica cultures a ring cleavage product was also
      found. While in the R. gluttinis assays the hydroxydibenzofuran was detected
      earlier, at 2 days' incubation time, in the other yeast experiments they were
      observed at the 4-5th incubation days with the maximum amounts at the 7th day.
      Our results confirmed the ability of autochthonous yeast species to hydroxylate
      dibenzofuran and to cleave the rings, and it is the first report for C. krusei,
      C. tenuis, P. anomala, P. haplophila and R. mucilaginosa. The ecological
      relevance of this study is based on the fact that dibenzofuran is a xenobiotic
      not easily transformed, so the catabolic activities observed in authochonous
      yeasts contribute to broadening the biodegradable substrate spectrum.

PMID- 12009136
TI  - Variation in CO2 assimilation rate induced by simulated dew waters with different
      sources of hydroxyl radical (*OH) on the needle surfaces of Japanese red pine
      (Pinus densifora Sieb. et Zucc.).
AB  - The hydroxyl radical (*OH) is generated in polluted dew on the needle surfaces of
      Japanese red pine (Pinus densiflora Sieb. et Zucc.). This free radical, which is
      a potent oxidant, is assumed to be a cause of ecophysiological disorders of
      declining trees on the urban-facing side of Mt. Gokurakuji, western Japan. Mists
      of *OH-generating N(III) (HNO2 and NO2-) and HOOH + Fe + oxalate solutions (50
      and 100 microM, pH 5.1-5.4) simulating the dew water were applied to the foliage
      of pine seedlings grown in open-top chambers in the early morning. Needles
      treated with 100 microM N(III) tended to have a greater maximum CO2 assimilation
      rate (Amax), a greater stomatal conductance (g(s)) and a greater needle nitrogen
      content (Nneedle), suggesting that N(III) mist acts as a fertilizer rather than
      as a phytotoxin. On the other hand, needles treated with 100 microM HOOH + Fe +
      oxalate solution showed the smallest Amax, g(s), and Nneedle, suggesting that the
      combination of HOOH + Fe + oxalate caused a decrease in needle productivity. The
      effects of HOOH + Fe + oxalate mist on pine needles were very similar to the
      symptoms of declining trees at Mt. Gokurakuji.

PMID- 12009137
TI  - Effects of leachate recirculation on biogas production from landfill co-disposal
      of municipal solid waste, sewage sludge and marine sediment.
AB  - Leachate recirculation is an emerging technology associated with the management
      of landfill. The impact of leachate recirculation on the co-disposal of three
      major wastes (municipal solid waste, sewage sludge and sediment dredgings) was
      investigated using a laboratory column study. Chemical parameters (pH, COD,
      ammoniacal-N, total-P) and gas production (total gas volume, production rates and
      concentrations of CH4 and CO2) were monitored for 11 weeks. Leachate
      recirculation reduced waste-stabilization time and was effective in enhancing gas
      production and improving leachate quality, especially in terms of COD. The
      results also indicated that leachate recirculation could maximize the efficiency
      and waste volume reduction rate of landfill sites.

PMID- 12009138
TI  - Composition of wet deposition in Kaynarca, Turkey.
AB  - In this work, composition of wet deposition in Kaynarca, Turkey is studied by
      collecting precipitation samples during more than a 2-year period. August 1993
      November 1995. Concentrations of the main cations Na+, Mg2+, Ca2+, K+, NH4+ and
      the main anions Cl-, NO3- and SO4(2-) together with pH were studied. The average
      pH value at Kaynarca was near neutral, 5.59. Results indicated that SO4(2-)
      concentration in precipitation was very high, as was Ca2+, neutralizing the
      acidity. Acidic wet deposition samples were generally obtained in winter.
      Enrichment factors for sea and soil indicate the strong effects of sea and soil,
      specifically limestone on the composition of precipitation. Non-sea salt
      fractions of SO4(2-) were found to range from 0.955 to 0.980, showing the effect
      of non-sea sources, especially emissions from fossil-fuel combustion, on the pH
      of samples. Trajectory analysis showed that cyclones originating from
      northwestern, central and eastern parts of Europe have generally high sulfate and
      nitrate concentrations and low pH.

PMID- 12009139
TI  - A mathematical modeling of sulphur dioxide pollution in Erzurum City.
AB  - A non-linear simple air-quality model was developed by applying the continuity
      equation for the air control volume over Erzurum city center and tested using
      daily average values of SO2 and meteorological data obtained during the winter
      seasons in Erzurum, Turkey from 1994 to 1998. Model parameters are estimated by
      non-linear regression analysis. Agreement between model predictions and measured
      data was found very satisfactory with standard deviations less than 20 microg/m3.

PMID- 12009140
TI  - Mobility of heavy metals associated with the natural weathering of coal mine
      spoils.
AB  - Knowledge of chemical mobility of heavy metals is fundamental to understanding
      their toxicity, bioavailability, and geochemical behavior. In this paper, two
      different methods, i.e. mineralogical means and sequential extractions, were
      employed to analyze the total contents, existing states, and chemical forms of
      heavy metals in coal mine spoils. The results demonstrate that the mobility of
      heavy metals in coal mine spoils depends not only on their existing states and
      the stability of their host minerals but also on the properties of the coal mine
      spoils. In the process of coal mine spoils-water interaction, sulfides that
      contain heavy metals first break down and release metals, which are then adsorbed
      and complexed by the iron oxyhydroxide colloid resulting from pyrite oxidization
      and organic matter. During the natural weathering of coal mine spoils, only a
      small fraction of these metals are released to the environment, and most of them
      still remains in the residual material.

PMID- 12009141
TI  - Role of loosely bound humic substances and humin in the bioavailability of
      phenanthrene aged in soil.
AB  - A study was conducted to determine a possible role of loosely bound humic
      substances (i.e., humic and fulvic acids) in bioavailability of aged phenanthrene
      with time. In this study, long-term residence of phenanthrene in soil is defined
      as aging or sequestration, and the effect was determined by the declined
      bioavailability to bacteria of the polycyclic aromatic hydrocarbon with increased
      residence time. After 1, 7, and 100 days of aging of phenanthrene in Lima loam,
      about 90-93% of initial phenanthrene was recovered from the humin-mineral
      fraction of Lima loam whereas less than 12% was found in humic and fulvic acids
      of the same soil. Mineralization rates of phenanthrene aged in the humin-mineral
      fraction significantly decreased with time by the test bacterium P5-2. In terms
      of extents of mineralization, the difference with time was not appreciable, but
      still significant at P<0.05. Additional decreases in the rates and extents of
      mineralization were observed with the whole soil (i.e. Lima loam) to which
      phenanthrene had been aged. Data suggest that major sequestration sites for
      phenanthrene may reside in the humin-mineral fraction, and probably humic and
      fulvic acids may act as a physico-chemical barrier to bacterial degradation so
      that the compound's bioavailability may be limited.

PMID- 12009142
TI  - In situ fixation of metals in soils using bauxite residue: chemical assessment.
AB  - Contamination of soils with heavy metals and metalloids is a widespread problem
      all over the world. Low cost, non-invasive, in situ technologies are required for
      remediation processes. We investigated the efficiency of a bauxite residue (red
      mud) to fix heavy metals in two soils, one contaminated by industrial activities
      (French soil), and one by sewage sludge applications (UK soil). This Fe-oxide
      rich material was compared with lime, or beringite, a modified aluminosilicate
      that has been used for in situ fixation processes. Four different crop species
      were successively grown in pots. Metal concentrations in the soil pore waters
      were analyzed during the growing cycles. At the end of the experiment fluxes of
      heavy metals were measured using a diffusive gradient in thin film technique
      (DGT). Furthermore, a sequential extraction procedure (SEP) and an acidification
      test were performed to investigate the mechanisms of metal fixation by different
      soil amendments. In both soils, the concentrations of metals in the soil pore
      water and metal fluxes were greatly decreased by the amendments. An application
      of 2% red mud performed as well as beringite applied at 5%. Increasing soil pH
      was a common mechanism of action for all the amendments. However, the red mud
      amendment shifted metals from the exchangeable to the Fe-oxide fraction, and
      decreased acid extractability of metals. The results suggest that specific
      chemisorption, and possibly metal diffusion into oxide particles could also be
      the mechanisms responsible for the fixation of metals by red mud.

PMID- 12009143
TI  - In situ fixation of metals in soils using bauxite residue: biological effects.
AB  - Soils polluted with heavy metals can cause phytotoxicity and exhibit impared
      microbial activities. In this paper we evaluate the responses of different
      biological endpoints to in situ remediation processes. Three soil amendments (red
      mud, beringite and lime) were applied to two soils polluted by heavy metals.
      Oilseed rape, wheat, pea and lettuce were grown successively in pots on the
      untreated and amended soils and their yield and metal uptake were determined. A
      suite of microbial tests (lux-marked biosensors, Biolog and soil microbial
      biomass) were performed to determine the effect of the soil amendments on the
      functionality and size of the soil microbial community. In both soils all three
      amendments reduced phytotoxicity of heavy metals, enhanced plant yields and
      decreased the metal concentrations in plants. The red mud treatment also
      increased soil microbial biomass significantly. The microbial biosensors
      responded positively to the remediation treatments in the industrially
      contaminated soil used in the experiment. Red mud applied at 2% of soil weight
      was as effective as beringite applied at 5%. The results also showed that since
      the biological systems tested respond differently to the alleviation of metal
      toxicity, a suite of biological assays should be used to assess soil remediation
      processes.

PMID- 12009144
TI  - The potential of Thai indigenous plant species for the phytoremediation of
      arsenic contaminated land.
AB  - To assess the potential of the native plant species for phytoremediation, plant
      and soil samples were collected from two areas in Thailand that have histories of
      arsenic pollution from mine tailings. The areas were the Ron Phibun District
      (Nakorn Si Thammarat province) and Bannang Sata District (Yala province), and
      samples were taken in 1998 and 1999 and analysed for total arsenic by atomic
      absorption spectrophotometry. Arsenic concentrations in soil ranged from 21 to
      14,000 microg g(-1) in Ron Phibun, and from 540 to 16,000 microg g(-1) in Bannang
      Sata. The criteria used for selecting plants for phytoremediation were: high As
      tolerance, high bioaccumulation factor, short life cycle, high propagation rate,
      wide distribution and large shoot biomass. Of 36 plant species, only two species
      of ferns (Pityrogramma calomelanos and Pteris vittata), a herb (Mimosa pudica),
      and a shrub (Melastoma malabrathricum), seemed suitable for phytoremediation. The
      ferns were by far the most proficient plants at accumulating arsenic from soil,
      attaining concentrations of up to 8350 microg g(-1) (dry mass) in the frond.

PMID- 12009145
TI  - Wind-induced deformations in a segmented mirror.
AB  - A Zernike expansion of wind-induced deformations in a segmented mirror is
      described. The wind model is a frozen turbulent field with a Kolmogorov spectrum
      for scales smaller than the outer scale and a flat spectrum for scales larger
      than the outer scale. The approach allows a mode-by-mode comparison of the wave
      front error contributions from atmospheric phase distortions, wind-induced
      deformations, and the mirror control system noise. This is used to design a
      controller that minimizes the mirror surface errors by application of corrections
      based on edge sensor measurements and wave-front measurements on a guide star.

PMID- 12009146
TI  - High-efficiency blazed diffractive optical elements for the violet wavelength
      fabricated by electron-beam lithography.
AB  - Blazed diffractive optical elements (DOEs) were studied for the violet wavelength
      by electron-beam lithography. By optimizing electron-beam writing parameters and
      electron-dose distributions, we fabricated eight kinds of grating (period A = 10
      0.54 microgm) with excellent blazed structure. It has been demonstrated that the
      measured diffraction efficiency values agreed well with the rigorous theoretical
      ones. For the fine period of 0.54 microm, we confirmed a peak appearance of 75.6%
      (TE) experimentally. A wave aberration as small as approximately 0.01 lambda
      (rms) was obtained for the first-order diffracted wave from the fabricated DOEs.
      Blazed DOEs for the violet wavelength could be used as key devices in a high
      density optical disk pickup of the next generation.

PMID- 12009147
TI  - Performance of normal-incidence molybdenum-yttrium multilayer-coated diffraction
      grating at a wavelength of 9 nm.
AB  - The first experimental investigation of a normal-incidence Mo-Y multilayer-coated
      diffraction grating operating at a 9-nm wavelength is reported. The substrate is
      a replica of a concave holographic ion-etched blazed grating with 2,400
      grooves/mm and a 2-m radius of curvature. The measured peak efficiency in the -3
      order is 2.7% at a wavelength of 8.79 nm. To our knowledge, this is the highest
      normal-incidence grating efficiency ever obtained in this wavelength region.

PMID- 12009148
TI  - Simultaneous determination of curvature, plane of curvature, and temperature by
      use of a miniaturized sensing head based on fiber Bragg gratings.
AB  - We present what we believe to be a novel miniaturized sensor configuration based
      on fiber Bragg gratings for simultaneous measurement of curvature and temperature
      in smart structures and composite materials. Because of the particular geometry
      of the sensing head, it is possible not only to measure the radius of curvature
      but also to determine the plane of curvature. We arrange three Bragg gratings in
      the vertices of the smallest equilateral triangle that can be defined by the
      cross sections of the fibers. The set is then inserted into a glue-filled
      capillary stainless-steel tube to provide both suitable protection for the Bragg
      sensors and rotational symmetry to the sensing head. This tube also ensures
      isolation from axial strain, allowing for the additional determination of
      temperature. The proposed sensing head is particularly well suited for
      applications in smart structures because it can be embedded along any layer of a
      composite material (including the neutral line) without special concern for the
      relative orientation of the Bragg gratings and the composite layers. We can also
      use this sensing configuration to implement more-sophisticated sensors dedicated,
      for example, to the measurement of multiaxial acceleration or flow and
      temperature.

PMID- 12009149
TI  - Analysis of Seidel aberration by use of the discrete wavelet transform.
AB  - Seidel aberration coefficients can be expressed by Zernike coefficients. The
      least-squares matrix-inversion method of determining Zernike coefficients from a
      sampled wave front with measurement noise has been found to be numerically
      unstable. We present a method of estimating the Seidel aberration coefficients by
      using a two-dimensional discrete wavelet transform. This method is applied to
      analyze the wave front of an optical system, and we obtain not only more-accurate
      Seidel aberration coefficients, but we also speed the computation. Three
      simulated wave fronts are fitted, and simulation results are shown for spherical
      aberration, coma, astigmatism, and defocus.

PMID- 12009150
TI  - Geometrical tomographic imaging of refractive indices through turbid media by a
      wavelength-scanning heterodyne interference confocal microscope.
AB  - A wavelength-scanning heterodyne interference confocal microscope has proved to
      provide the tomographic image of the refractive indices of transparent and turbid
      media on the scale of geometrical depth when weakly reflected light with an
      optical power as low as of the order of 10(-14) W is used. The refractive indices
      of the transparent object and the turbid media were measured with accuracies of 
      0.5% and approximately 3%, respectively. This imaging method is advantageous for
      evaluating quantitative refractive indices and internal structures.

PMID- 12009151
TI  - Characterization of a CCD-based digital x-ray imaging system for small-animal
      studies: properties of spatial resolution.
AB  - A digital x-ray imaging system was designed for small-animal studies. This system
      is a fiber-optics taper-coupled imaging system with two CCD arrays uniquely
      jointed. The x-ray source of the system has a small focal spot of 20 microm. This
      digital imaging system contains specially designed shelves to provide
      magnification levels, ranging from 1.5x to 5x. The system is characterized in
      terms of its properties of spatial resolution. An observer-based spatial
      resolution measurement was conducted with a line-pair target and a sector test
      pattern. The modulation transfer function of the system, with different
      magnifications, was studied by use of a 10-microm lead slit. The average
      resolutions at 50% and 5% modulations at 1x magnification were measured as 3.9
      and 8.4 lp/mm, respectively, where lp indicates line pairs. With 5x
      magnification, the 50% and the 5% modulations provided 13.2- and 29.9-lp/mm,
      respectively, average spatial resolutions. The measurements showed consistency
      between the two individual CCD arrays; the difference in resolution between the
      two CCDs is less than 1%, even at high magnifications.

PMID- 12009152
TI  - Polarization-dependent angular-optical reflectance in solar-selective
      SnOx:F/Al2O3/Al reflector surfaces.
AB  - Polarization-dependent angular-optical properties of spectrally selective
      reflector surfaces of fluorine-doped tin oxide (SnOx:F) deposited pyrolytically
      on anodized aluminum are reported. The angular-reflectance measurements, for
      which both s- and p-polarized light are used in the solar wavelength range 0.3
      2.5 microm, reveal strong spectral selectivity, and the angular behavior is
      highly dependent on the polarizing component of the incident beam, the total film
      thickness, and the individual thickness of the Al2O3 and the SnO2:F layers. The
      anodic A12O3 layers were produced electrochemically and varied between 100 and
      205 nm in thickness. The SnOx:F films were grown pyrolytically at a temperature
      of 400 degrees C with film thicknesses varying in the range 180-320 nm. The
      reflectors were aimed at silicon solar cells, and good spectrally selective
      reflector characteristics were achieved with these thinly preanodized, SnOx:F/Al
      samples; that is, high cell reflectance was obtained for wavelengths below 1.1
      microm and low thermal reflectance for wavelengths above 1.1 microm, with the
      best samples having values of 0.80 and 0.42, respectively, at near-normal angles
      of incidence. This corresponds to an anodic layer thickness of 155 nm. Both the
      angular calculations and the experimental measurements show that the cell
      reflectance is relatively insensitive to the incidence angle, and a low thermal
      reflectance is maintained up to an angle of approximately 60 degrees.

PMID- 12009153
TI  - Tilt-compensating algorithm for phase-shift interferometry.
AB  - A self-calibrating algorithm for phase-shift interferometry is described that is
      able to cancel the effect of accidental relative tilts that may occur during
      phase stepping. The algorithm is able to retrieve both the phase steps and the
      tilts that accompany them. Only three phase-shifted interferograms are needed,
      and no other information about the intentional phase shifts or possible tilts has
      to be supplied. This purpose is achieved by division of the interferogram space
      into blocks on which a previously reported self-calibrating algorithm is applied
      and the actual values of the local phase shifts are calculated. The information
      thus obtained is used for extracting the global shift and tilt values. Further
      improvement in the results is achieved by means of a fitting routine.

PMID- 12009154
TI  - Dual-wave-front computer-generated holograms for quasi-absolute testing of
      aspherics.
AB  - Testing of aspherics by means of computer-generated holograms (CGHs) is well
      known. To perform a quasi-absolute test of rotationally symmetric aspheric
      surfaces, two wave fronts must be encoded in the CGH. Both the null lens and a
      spherical lens have to be stored. This enables successive measurements of the
      aspheric and of a cat's-eye position without changing the object arm of the
      interferometer. Two possibilities for encoding both wave fronts have been
      investigated. A first-order approximation for estimating the influence of
      disturbing diffraction orders is given.

PMID- 12009155
TI  - Grating-based real-time polarization phase-shifting interferometry: error
      analysis.
AB  - A phase Ronchi grating-based real-time polarization phase-shifting method can be
      efficiently used for dynamic phase measurement in optical interferometry. A
      thorough error analysis is required for exhibiting how error sources influence
      phase-measurement results. We analyze the phase-measurement errors that are
      induced by the retardation error and azimuth angle error of the quarter-wave
      plate, the azimuth angle error of polarizers, the phase and intensity aberrations
      of diffractive wave fronts, and pixel mismatch of the interferometric patterns.
      The results will also be useful for evaluating the phase-measurement accuracy of
      other similar systems.

PMID- 12009156
TI  - Real-time speckle interferometry fringe formation with an adaptive phase mask.
AB  - We describe what we believe is a novel speckle-pattern interferometry method of
      applying a spatial light modulator (SLM) as an adaptive phase mask to obtain real
      time fringes of a deformed object without using conventional correlation methods
      of electronic subtraction or addition. The method is to use a SLM to cancel
      initial phase in the speckled image before the object is deformed. The fringes
      from the deformed object can be visualized directly after the initial phase has
      been canceled. A commercial liquid-crystal television is used as a SLM. The
      performance of using this SLM in an out-of-plane speckle interferometer is
      demonstrated.

PMID- 12009157
TI  - Stabilization by harmonic intensities for the output signal in heterodyne
      detection.
AB  - We experimentally demonstrated that the technique to stabilize the output signal
      by harmonic intensities is useful in heterodyne detection with an incoherent
      light source such as a halogen lamp. The relation between the relative standard
      deviation of an output signal and the fluctuation of the light intensity is
      analyzed and simulated. Using the fundamental to sixth harmonics increases the
      stabilities of output signal approximately 3 times, and subtracting the relative
      standard deviation of the intensity of light source enhances the stabilities 49
      times. The fluctuating phase that is due to the fluctuating frequency and
      temperature and its power spectrum density for an interferometer is also
      calculated with the Allan variance.

PMID- 12009158
TI  - Design of a broadband UV-visible alpha-barium borate polarizer.
AB  - Until recently, the construction of polarizers for operation below approximately
      260 nm were limited to materials such as magnesium fluoride and crystalline
      quartz. These materials have a much smaller birefringence than calcite, but
      unlike calcite they have good transmission below 200 nm. These materials are,
      however, not well suited for Glan-Taylor-type polarizer designs, as they do not
      produce a large angular separation of the polarized components. A new material, a
      barium borate, has recently become available, which transmits to just below 200
      nm and has a birefringence that approaches that of calcite. We analyze the
      performance of various polarizer designs that use this material. Results are
      presented that compare theory with experimental investigation of a manufactured
      device.

PMID- 12009159
TI  - Phase anomalies in fourier-transform spectrometers: an absorbing beam splitter is
      neither sufficient nor necessary.
AB  - Recently it has been a topic of some discussion that the phase associated with
      part of the self-emission of a Fourier-transform spectrometer may differ neither
      by 0 nor by pi rad from the phase of an external target if there is absorption in
      the beam splitter. The conventional interpretation of this has been to separate
      the self-emission into three terms: instrument emission from the input port, in
      phase with the external target; emission from the secondary input port, pi rad
      from the target; and emission from an absorbing beam splitter with an anomalous
      phase (neither 0 nor pi rad with respect to the target). There is another
      necessary condition that has not received much attention, that the instrument not
      be isothermal. For polarized radiation there is an additional condition that
      suppresses the anomalous phase, and for unpolarized radiation there is a way to
      produce an anomalous phase without beam-splitter absorption.

PMID- 12009160
TI  - Optimization of a dual-rotating-retarder Mueller matrix polarimeter.
AB  - The dual-rotating-retarder configuration is one of the most common forms of the
      Mueller matrix polarimeter. I perform an optimization of this polarimeter
      configuration by minimizing the condition number of the system data reduction
      matrix. I find the optimum retardance for the rotating retarders to be 127
      degrees. If exactly 16 intensity measurements are used for a Mueller matrix
      calculation, a complex relationship exists between the condition number and the
      sizes of the angular increments of the two retarders. If many intensity
      measurements are made, thus overspecifying the calculation, I find broad optimal
      ranges of angular increments of the two retarders that yield essentially equal
      performance. Experimental results are given.

PMID- 12009161
TI  - Trapping forces, force constants, and potential depths for dielectric spheres in
      the presence of spherical aberrations.
AB  - We present and verify a theoretical model that predicts trapping forces (escape
      forces), force constants (trap stiffnesses), and trapping potential depths for
      dielectric spheres with diameters smaller than or equal to the wavelength of the
      trapping light. Optical forces can be calculated for arbitrary incident light
      distributions with a two-component approach that determines the gradient and the
      scattering force separately. We investigate the influence of spherical
      aberrations that are due to refractive-index mismatch on the maximum trapping
      force, the force constant, and the potential depth of a trap, which are important
      for optical tweezer applications. The relationships between the three parameters
      are explained and studied for different degrees of spherical aberration and
      various spheres (refractive indices n(s) = 1.39-1.57, radii a = 0.1-0.5 microm,
      lambda(0) = 1.064 microm). We find that all three parameters decrease when the
      distance to the coverslip increases. Effects that could make the interpretation
      of experimental results ambiguous are simulated and explained. Computational
      results are compared with the experimental data found in the literature. A good
      coincidence can be established.

PMID- 12009162
TI  - Absolute refractive indices and thermal coefficients of CaF2, SrF2, BaF2, and LiF
      near 157 nm.
AB  - We present high-accuracy measurements for wavelengths near 157 nm of the absolute
      index of refraction, the index dispersion, and the temperature dependence of the
      index for the ultraviolet optical materials with cubic symmetry: CaF2, SrF2,
      BaF2, and LiF. Accurate values of these quantities for these materials are needed
      for designs of the lens systems for F2 excimer-laser-based exposure tools for 157
      nm photolithography. These tools are expected to use CaF2 as the primary optical
      material and possibly one of the others to correct for chromatic aberrations.
      These optical properties were measured by the minimum deviation method. Absolute
      refractive indices were obtained with an absolute accuracy of 5 x 10(-6) to 6 x
      10(-6).

PMID- 12009163
TI  - Surface plasmon resonance sensor using an optical fiber with an inverted graded
      index profile.
AB  - A new optical fiber sensor based on surface plasmon resonance is described. It
      uses an optical fiber with an inverted graded-index profile. A theoretical
      analysis of the optical propagation when a point light source was used and a
      computation of the optical power transmitted by the fiber were performed.
      Experiments were carried out to measure changes of the transmitted power caused
      by refractive-index variations of the surrounding dielectric medium. Both the
      simulation and experiments have shown that the sensor exhibits high sensitivity
      for changes of the surrounding medium in a refractive index range from 1.33 to
      1.39.

PMID- 12009164
TI  - Matrix description of coherent and incoherent light reflection and transmission
      by anisotropic multilayer structures.
AB  - We propose a matrix method for the description of light reflection and
      transmission by an anisotropic multilayer system consisting of thin and thick
      layers. A method based on partial-wave matrix summations is applicable in the
      field of reflection and transmission photometry and ellipsometry. In the case of
      a thin anisotropic film, the interference effects were described by use of a
      coherent summation of Jones matrices. Incoherent intensity summations for a thick
      weakly anisotropic layer were characterized by use of the coherency vector
      formalism. Observable quantities or Mueller matrix components were obtained from
      the matrix describing transformation of the coherence vectors.

PMID- 12009165
TI  - Detection of bacterial infection of agave plants by laser-induced fluorescence.
AB  - Greenhouse-grown plants of Agave tequilana Weber var. azul were inoculated with
      Erwinia carotovora, the causal agent of stem soft rot. We investigated the laser
      induced fluorescence (LIF) of agave plants to determine whether LIF can be used
      as a noninvasive sensing tool for pathological studies. The LIF technique was
      also investigated as a means of detecting the effect of the polyamine
      biosynthesis inhibitor beta-hydroxyethylhydrazine as a bactericide against the
      pathogenic bacterium Erwinia carotovora. A He-Ne laser at 632.8 nm was used as
      the excitation source, and in vivo fluorescence emission spectra were recorded in
      the 660-790-range. Fluorescence maxima were at 690 and 740 nm. The infected
      plants that were untreated with the bactericide showed a definite increase in
      fluorescence intensity at both maxima within the first three days after
      infection. Beginning on the fifth day, a steady decrease in fluorescence
      intensity was observed, with a greater effect at 740 than at 690 nm. After 30
      days there was no fluorescence. The infected plants that had been treated with
      the bactericide showed no significant change in fluorescence compared with that
      of the uninfected plants. The ratio of fluorescence intensities was determined to
      be F 690 nm/F 740 nm for all treatments. These studies indicate that LIF
      measurements of agave plants may be used for the early detection of certain types
      of disease and for determining the effect of a bactericide on bacteria. The
      results also showed that fluorescence intensity ratios can be used as a reliable
      indicator of the progress of disease.

PMID- 12009166
TI  - Index determination of opaque and semitransparent metallic films: application to
      light absorbers.
AB  - Index-determination methods based on reflectance and transmittance measurements
      are developed for both opaque and semitransparent metallic films. Results are
      given concerning chromium and nickel layers manufactured by electron-beam
      deposition. To take account of the evolution of the optical constants versus
      layer thickness, an inhomogeneous layer model is used, which permits us to obtain
      a good agreement between measurements and calculations. Results are applied to
      the design and manufacture of light absorbers for which accurate index knowledge
      is required. Measured absorption is higher than 0.999 on both broadband and
      monochromatic components.

PMID- 12009167
TI  - Effect of systematic errors in spectral photometric data on the accuracy of
      determination of optical parameters of dielectric thin films.
AB  - The determination of optical parameters of thin films from experimental data is a
      typical task in the field of optical-coating technology. The optical
      characterization of a single layer deposited on a substrate with known optical
      parameters is widely used for this purpose. Results of optical characterization
      are dependent on not only the choice of the thin-film model but also on the
      quality of experimental data. The theoretical results presented highlight the
      effect of systematic errors in measurement data on the determination of thin-film
      parameters. Application of these theoretical results is illustrated by the
      analysis of experimental data for magnesium fluoride thin films.

PMID- 12009168
TI  - SPIFI: a direct-detection imaging spectrometer for submillimeter wavelengths.
AB  - The South Pole Imaging Fabry-Perot Interferometer (SPIFI) is the first instrument
      of its kind-a direct-detection imaging spectrometer for astronomy in the
      submillimeter band. SPIFI's focal plane is a square array of 25 silicon
      bolometers cooled to 60 mK; the spectrometer consists of two cryogenic scanning
      Fabry-Perot interferometers in series with a 60-mK bandpass filter. The
      instrument operates in the short submillimeter windows (350 and 450 microm)
      available from the ground, with spectral resolving power selectable between 500
      and 10,000. At present, SPIFI's sensitivity is within a factor of 1.5-3 of the
      photon background limit, comparable with the best heterodyne spectrometers. The
      instrument's large bandwidth and mapping capability provide substantial
      advantages for specific astrophysical projects, including deep extragalactic
      observations. We present the motivation for and design of SPIFI and its
      operational characteristics on the telescope.

PMID- 12009169
TI  - Patterning flood illumination with microlens arrays.
AB  - We describe a convenient lithographic technique that can produce simple,
      repetitive micropatterns over large areas (several square centimeters). The
      technique uses an illuminated array of micrometer-scale lenses to generate an
      array of optical patterns in an image plane located within micrometer distances
      from the lens array. A layer of photoresist, placed in the image plane, records
      the patterns. Microlenses with different sizes, profiles, composition, and
      indices of refraction produce corresponding patterns in exposed and developed
      photoresist. Both spherical and nonspherical microlenses were examined. Several
      types of optical element containing arrays of microlenses were fabricated and
      used to demonstrate that this technique can generate uniform micropatterns over
      large areas (>4 cm2) in a single exposure. The smallest features produced had
      dimensions of approximately 100 nm.

PMID- 12009170
TI  - Tolerance on defocus precisely locates the far field (exactly where is that far
      field anyway?).
AB  - The Fraunhofer criterion defines the location of the boundary between the Fresnel
      and the Fraunhofer diffraction regions and thus determines the location of that
      region commonly referred to as the far field. The Fraunhofer criterion is usually
      given as an axial distance much greater than some amount relative to the maximum
      dimension of the aperture. By recognizing that Fresnel diffraction patterns are
      merely defocused Fraunhofer diffraction patterns, we show that the Fraunhofer
      criterion can be written precisely in terms of an allowable tolerance on defocus.
      This new criterion provides insight that is useful to optical designers and
      engineers who routinely deal with such tolerances.

PMID- 12009171
TI  - Polarization-mode dispersion measurements in high-birefringence fibers by means
      of stimulated Raman scattering.
AB  - A convenient technique for polarization-mode dispersion measurements in short
      lengths of high-birefringence fibers is reported. The technique is based on
      spectral interferometry with a frequency-doubled Nd:YAG laser, which is frequency
      shifted and broadened by self-stimulated Raman scattering in an optical fiber.
      The different Raman Stokes beams permit accurate measurements over a 40-nm
      wavelength range in the visible spectrum.

PMID- 12009172
TI  - Analytical study of the principal angle used in optical experiments.
AB  - An analytical method has been developed for directly calculating the principal
      angle theta(p) at which the phase difference between the two reflection
      coefficients is equal to 90 degrees and at which the ratio of /r(p)/ to /r(s)/ is
      equal or close to a minimum. The equations given here can be used in many optical
      applications. For example, ellipsometric data measured at an incidence angle
      theta(p) will have higher precision than data measured at other incidence angles.
      theta(p) is the principal angle. Instead of three principal angles, there is only
      one principal angle, which can be found in the region of 0 < or = theta(p) < or =
      90 degrees for most metallic materials used in applications. Results show good
      agreement between the measured and the calculated spectra of delta(p) and
      rho(po).

PMID- 12009173
TI  - Pitch and loudness interact in auditory displays: can the data get lost in the
      map?
AB  - Many auditory displays use acoustic attributes such as frequency, intensity, and
      spectral content to represent different characteristics of multidimensional data.
      This study demonstrated a perceptual interaction between dynamic changes in pitch
      and loudness, as well as perceived asymmetries in directional acoustic change,
      that distorted the data relations represented in an auditory display. Three
      experiments showed that changes in loudness can influence pitch change, that
      changes in pitch can influence loudness change, and that increases in acoustic
      intensity are judged to change more than equivalent decreases. Within a
      sonification of stock market data, these characteristics created perceptual
      distortions in the data set. The results suggest that great care should be
      exercised when using lower level acoustic dimensions to represent
      multidimensional data.

PMID- 12009174
TI  - Immediate and persisting effects of misleading questions and hypnosis on memory
      reports.
AB  - Immediate and persisting effects of misleading questions and hypnosis on memory
      reports were assessed. After listening to a story, 52 highly suggestible students
      and 59 low and medium suggestible students were asked misleading or neutral
      questions in or out of hypnosis. All participants were then asked neutral
      questions without hypnosis. Both hypnosis and misleading questions significantly
      increased memory errors, and misleading questions produced significantly more
      errors than did hypnosis. The 2 effects were additive, so that misleading
      questions in hypnosis produced the greatest number of errors. There were no
      significant interactions with level of hypnotic suggestibility. Implications of
      these findings for the per se exclusion of posthypnotic testimony are discussed.

PMID- 12009175
TI  - Selecting accurate statements from the cognitive interview using confidence
      ratings.
AB  - Participants viewed a videotape of a simulated murder, and their recall (and
      confidence) was tested 1 week later with the cognitive interview. Results
      indicated that (a) the subset of statements assigned high confidence was more
      accurate than the full set of statements; (b) the accuracy benefit was limited to
      information that forensic experts considered relevant to an investigation,
      whereas peripheral information showed the opposite pattern; (c) the confidence
      accuracy relationship was higher for relevant than for peripheral information;
      (d) the focused-retrieval phase was associated with a greater proportion of
      peripheral and a lesser proportion of relevant information than the other phases;
      and (e) only about 50% of the relevant information was elicited, and most of this
      was elicited in Phase 1.

PMID- 12009176
TI  - The confidence-accuracy relationship in eyewitness identification: the effects of
      reflection and disconfirmation on correlation and calibration.
AB  - Participants viewed a simulated crime and attempted an identification from an 8
      person target-present or target-absent lineup. The authors examined
      identification confidence-accuracy relations, contrasting a control condition (n
      = 310) with 2 manipulations designed to improve confidence scaling. Before
      indicating confidence, participants reflected on encoding and identification test
      conditions (n = 316) or suggested hypotheses about why their identification
      decision might have been wrong (n = 318). Confidence-accuracy correlations were
      weak and did not differ across conditions. However, for positive identifications,
      confidence and accuracy were well calibrated in the experimental conditions,
      although not in the control condition; similar patterns were observed for lineup
      rejections. Explanations for calibration differences in terms of discrimination
      difficulty, (mis)match between encoding and test stimuli, and the availability of
      confidence cues were advanced.

PMID- 12009177
TI  - Speed of comprehension of visualized ordered sets.
AB  - The authors investigated the effects of visual properties of hierarchical graphs
      on speed of comprehension: planarity (crossing of lines), slopes (orientation of
      lines), and levels (adjustment of dots). In each of 4 experiments, 30
      participants responded to interpretive questions that required comparisons among
      the elements of the graph. Knowledge provided to participants differed across
      Experiments 1a, 1b, and 1c; question demands varied in Experiment 2. Analysis of
      response latencies showed that crossing of lines is the most influential variable
      independent of orientation, dot adjustment, and question demands. Speed of
      comprehension decreased with increasing question demands. When question demands
      were high, orientation of lines also had an effect on speed of comprehension.
      Preliminary conclusions for the presentation of hierarchical graphs are drawn.

PMID- 12009178
TI  - When paying attention becomes counterproductive: impact of divided versus skill
      focused attention on novice and experienced performance of sensorimotor skills.
AB  - Two experiments examined the impact of attention on sensorimotor skills. In
      Experiment 1, experienced golfers putted under dual-task conditions designed to
      distract attention from putting and under skill-focused conditions that prompted
      attention to step-by-step putting performance. Dual-task condition putting was
      more accurate. In Experiment 2, right-footed novice and experienced soccer
      players dribbled through a slalom course under dual-task or skill-focused
      conditions. When using their dominant right foot, experts again performed better
      in the dual-task condition. However, when using their less proficient left foot,
      experts performed better in the skill-focused condition. Novices performed better
      under skill-focus regardless of foot. Whereas novices and the less-proficient
      performances of experts benefit from online attentional monitoring of step-by
      step performance, high-level skill execution is harmed.

PMID- 12009179
TI  - Effects of locally-delivered human macrophage products and estrogen on murine
      inflammatory bone resorption.
AB  - The objective of this study was to use an in vivo model of periodontitis (mouse
      calvaria) to quantify the effects of local release of secreted human macrophage
      products, 17beta-estradiol (E2), and proinflammatory lipopolysaccharide (LPS) on
      histologic bone resorption. Human THP-1 monocytes (106) were converted to
      macrophage phenotype by 500 ng/ml phorbol 12-myristate- 13-acetate (PMA) and
      treated as follows: no stimulation or Escherichia coli LPS (10 microg/ml) alone
      or in combination with a physiologic dose of E2 (100 pg/ml) for 24 h in RPMI/10%
      FBS, washed extensively, then incubated for 24 h in serum-free media. Supernatant
      products were concentrated and incorporated into a 4% (w/v) methylcellulose gel.
      Separate gels were incorporated with the following: LPS (500 microg/animal)
      alone, high dose of E2 (10 ng/animal) alone, a combination of LPS + E2, or gel
      only (controls). Loaded or control gels were placed into a polylactic acid
      occlusive dome, inserted subcutaneously over the calvaria of mature
      ovariectomized ICR Swiss mice (8 mice x 7 groups x 2 times [5/14 days] = 112
      animals), then calvaria were evaluated histologically. Macrophage stimulation
      with LPS alone, but not LPS in combination with E2, produced supernatants which
      upregulated osteoclast numbers in the suture area compared to gel controls at 5
      days (p = 0.009). The addition of LPS directly to the local delivery gels
      significantly upregulated osteoclasts in endosteal surfaces compared to gel
      controls at 5 days (p = 0.024) and at 14 days (p = 0.025). The addition of E2 to
      LPS down-regulated resorption to a level not different from gel controls at 14
      days. This in vivo model appears effective in studying inflammatory bone
      resorption, which may be inhibited by E2 directly or through its influence on
      secreted macrophage products.

PMID- 12009180
TI  - Evaluation of physiological tooth movements within clinically normal periodontal
      tissues by means of periodontal pulsation measurements.
AB  - The three-dimensional physiological tooth movement synchronized with heartbeat,
      periodontal pulsation, has already been demonstrated by previous researchers. The
      purpose of this study was to estimate physiological tooth movements within
      clinically normal periodontal tissues, thus establishing periodontal pulsation
      standards. The measuring device consisted of an amorphous sensor and a small
      magnet, which could detect tooth displacement without coming into contact with
      the tooth surface. The samples consisted of the left maxillary central incisors
      of 23 adult subjects. Three points on the labial surface were used as reference
      points to measure the labial-lingual movement range, and a point on the incisal
      edge was used for measuring the incisal-apical movement range. Periodontal
      pulsation and electrocardiogram measurements were recorded simultaneously for six
      minutes. The results showed that the mean amplitude of periodontal pulsation
      concerning the labial-lingual movement range was equal at the three labial points
      (0.59 microm) and tended to be smaller than that of the incisal-apical movement
      range (0.87 microm). There were no significant differences in the mean amplitude
      of periodontal pulsation at any of the four reference points. Significant
      correlations of the amplitude of periodontal pulsation existed among the three
      labial points. Though most teeth pulsated uniformly to the labial direction, some
      teeth moved in a complex manner including rotation with an axis among the three
      labial points. These results suggest that the values of periodontal pulsation
      amplitude which were recorded employing the amorphous sensor device are reliable
      standards of periodontal pulsation within clinically normal periodontal tissues.

PMID- 12009181
TI  - Cell proliferation and cell death in periodontal ligaments during orthodontic
      tooth movement.
AB  - The purpose of this study was to investigate cellular responses of periodontal
      ligaments during tooth movement. Twenty-eight male Sprague-Dawley rats, weighing
      200-250 g each, were used. To create the orthodontic force, elastic rubber blocks
      (0.65 mm thick) were inserted between the maxillary first and second molars on
      both sides. On days 3, 7, 10, 14, 21 and 28 after rubber block insertion,
      histopathological changes in both the tension and the pressure sides were
      examined by immunohistochemistry using proliferating cell nuclear antigen (PCNA)
      and by the TUNEL method. The ratios of PCNA-positive cells on the tension side 3
      and 7 days after rubber block insertion were higher than those on the pressure
      side. The ratios of PCNA-positive cells on the tension side were highest at day 3
      after insertion and then decreased during the remainder of the experimental
      period. On the pressure side, the ratios of PCNA-positive cells increased up to
      day 10 post insertion, then decreased from 14 to 28 days. The ratios of TUNEL
      positive cells on both the tension and the pressure sides increased throughout
      the entire experimental period. These results indicate that the periodontal
      ligaments on the tension side are able to respond more promptly to orthodontic
      forces than those on the pressure side. The data also suggest that the ratios of
      cell proliferation and of cell death are closely related to the regeneration and
      reconstruction of periodontal ligaments which reflect the orthodontic force.

PMID- 12009182
TI  - Methodology of three-dimensional determination of root surface roughness.
AB  - In comparing and evaluating the instruments that are used in root debridement,
      roughness constitutes a standard variable that is assessed. The purpose of this
      study was to describe the conditions and requirements for the three-dimensional
      roughness measurements of tooth roots using a laser profilometer. Impressions
      were made of 60 instrumented and 12 untreated root surfaces, which were then
      measured using a dynamically focussing optical profilometer (Mikrofocus, UBM,
      Karlsruhe, Germany). To separate roughness from the form of the tooth, a low pass
      filter was applied. This meant that the longer wavelengths - which roughly
      approximated the root forms - were subtracted from the measured profile. We then
      used an individualized Fourier transformation to define the threshold at which
      roughness becomes waviness. Roughness parameters were Ra (average roughness) and
      Rz (average roughness in the z dimension) for two- and three-dimensional
      measurements. To describe the requirements for the measurement, we studied the
      effect of pixel density and the field size on the average roughness value, Ra. We
      found that Ra increases with pixel density until 400 per mm is reached, after
      which it does not change meaningfully. Furthermore, Ra is highly dependent upon
      the area of the field to be scanned, increasing in line with the area, and does
      not approach one value within the surface available on one tooth. The correlation
      coefficients between the two-dimensional and three-dimensional Ra and Rz values
      ranged from 0.7 to 0.8. We conclude that roughness values are strongly dependent
      on the measurement conditions and the results of one study cannot be directly
      compared to another. In addition, it was found that two-dimensional measurements
      are sufficient for characterizing root surfaces.

PMID- 12009183
TI  - Serum IgG antibody response to periodontal pathogens in minority populations:
      relationship to periodontal disease status and progression.
AB  - Differences in periodontal disease prevalence, severity, subgingival microflora
      and host immune response have been reported for various ethnic/racial groups,
      which implies that risk factors for destructive periodontal disease progression
      may also vary in these populations. As it is possible that these differences may
      be due to confounding variables other than ethnicity/race, we have measured serum
      IgG antibody response to six periodontal pathogens, and compared these data with
      microbiological, clinical and demographic parameters in three urban minority
      populations. The study population consisted of 23 Asiatic, 48 African-American
      and 37 Hispanic subjects, who were resident in the greater New York region.
      Clinical indices that were recorded included pocket depth, attachment level,
      gingival erythema, bleeding upon probing, suppuration and supragingival plaque.
      Attachment level measurements were taken twice at each visit, and the difference
      between the means of pairs of measurements taken at baseline and two months later
      was used to determine disease progression. Subgingival microbiological species
      were identified and enumerated using DNA-DNA checkerboard hybridization. Serum
      IgG antibody levels to Actinobacillus actinomycetemcomitans serotyopes a and b,
      Bacteroides forsythus, Campylobacter rectus, Porphyromonas gingivalis and
      Prevotella intermedia were measured by enzyme-linked immunosorbant assay (ELISA).
      Mean serum IgG antibody to P. gingivalis was found to be higher in the African
      American group, while IgG antibody to B. forsythus was lower in the Hispanic
      group. However, the African-American group also had greater mean probing depth,
      attachment loss, number of missing teeth and numbers of individuals within the
      unskilled occupational group. When the data were analyzed by occupational status,
      mean serum IgG antibody to P. gingivalis increased from professional to skilled
      to unskilled groups. For the entire study population, prior disease and
      subsequent attachment loss were associated with elevated serum IgG antibody to P.
      gingivalis. Increasing pocket depth, attachment level, gingival erythema and age
      were also positively correlated with serum IgG antibody to P. gingivalis, but not
      with serum IgG antibody to the other five subgingival species. No correlation was
      found between whole-mouth bacterial levels and homologous serum IgG antibody
      levels. These results suggest that elevated serum IgG antibody to P. gingivalis
      reflects destructive periodontal disease status, and may be considered a risk
      factor for disease progression in these ethnic/racial populations. In addition,
      although differences in serum IgG antibody profiles to subgingival species were
      found among the three ethnic/racial groups, environmental and socioeconomic
      variables may have a greater influence on serum IgG antibody levels in these
      populations.

PMID- 12009184
TI  - Comparison of conventional and TACT (Tuned Aperture Computed Tomography) digital
      subtraction radiography in detection of pericrestal bone-gain.
AB  - Tuned Aperture Computed Tomography or TACT is a relatively new technique that
      transforms correlated two-dimensional images into a three-dimensional display.
      Associating TACT with digital subtraction radiography (TACT-DSR) may enhance its
      use in the detection of diseases. This study aims to assess observer performance
      in the task of detecting simulated bone-gain in periodontal defects, comparing
      conventional and TACT DSR. Buccal, lingual and proximal pericrestal bony defects
      in a human dry skull were imaged with and without increments of crushed-bone and
      wax mixtures using standardized vertical bitewing projections, acquired with an
      intraoral digital receptor in a tomographic X-ray machine. One hundred and twenty
      pairs of baseline and follow-up images were obtained for each imaging modality.
      Post-acquisition processing including image-registration, density-correction and
      subtraction operation were applied to both transmission images and TACT-slices.
      Eight calibrated observers evaluated the presence or absence of pericrestal bone
      gain using a 5-point confidence scale. Details about the location of periodontal
      defects and the amount of bone-gain for each subtracted image were recorded and
      used in the statistical analysis. Observer performance and study design factors
      were analyzed by means of receiver operating characteristic (ROC) curve analysis
      and ANOVA. Mean values of areas under ROC curves for bone-gain detection
      performance were 0.82 for conventional DSR and 0.90 for TACT-DSR. TACT-DSR
      provided statistically superior detection performance of simulated periodontal
      bone-gain over conventional DSR for tooth-obscured defects (p = 0.001) and for
      the smallest bone mass (p = 0.024). The findings support TACT-DSR's potential to
      provide greater sensitivity and technique flexibility in detecting periodontal
      bone-gain than standard DSR.

PMID- 12009185
TI  - Localization of the chemokine interleukin-8 and interleukin-8 receptors in human
      gingiva and cultured gingival keratinocytes.
AB  - Interleukin-8 (IL-8) has been implicated in a wide variety of diseases. Previous
      studies have demonstrated the expression of IL-8 in periodontal tissues, yet
      little is known about the exact source(s), mechanisms and factors involved in
      gingival expression of IL-8. Additionally, nothing is known about the presence
      and distribution of IL-8 receptors (IL-8R) in gingival cells. Therefore it was
      hypothesized that, in vivo, periodontal pathogens induce IL-8 expression from
      gingival keratinocytes (GK) which enhances leukocyte, microvascular endothelial
      cell (MVEC) and GK migration via specific IL-8 receptors present on these cells.
      The objective of the present study was to determine the distribution of IL-8 and
      IL-8R in gingival tissues and cultured human GK in vitro. Standard
      immunohistochemical and immunocytochemical techniques were utilized in order to
      localize IL-8 and its receptors CXCR-1 and CXCR-2 in archival gingival specimens
      (eight periodontitis and four non-inflamed controls) and in cultured gingival
      keratinocytes. It was demonstrated that, in vivo, IL-8 and IL-8R were present in
      gingival epithelium, MVEC and leukocytes. In vitro studies verified the above
      results, by showing expression of IL-8 and IL-8R in cultured gingival
      keratinocytes. It is concluded that IL-8 and IL-8 receptors are expressed in
      gingival epithelium both in vivo and in vitro. This new evidence indicates that
      epithelium plays a critical role in the host defense against invading pathogens
      and that keratinocytes can actively respond to IL-8 and other host cytokines, via
      specific receptors.

PMID- 12009186
TI  - Effects of ovariectomy on trabecular structures of rat alveolar bone.
AB  - An association between postmenopausal osteoporosis and tooth loss has been
      proposed. However, histomorphometrical changes in alveolar bone following
      estrogen deficiency are rarely reported with data on microtrabecular structural
      changes. To clarify the relationship between estrogen deficiency and tooth loss,
      we histomorphometrically analyzed the trabecular structural changes of mandibular
      alveolar bone in ovariectomized rats. Twenty-four adult female Fischer rats were
      used. Eight rats were sacrificed on day 0 (baseline). The remaining 16 rats were
      divided into two groups. One group was ovariectomized bilaterally (OVX) and the
      other group was subjected to sham surgery (Sham). After administration of
      tetracycline and calcein, the animals were sacrificed 60 days after surgery. Bone
      histomorphometry, node-strut analysis and measurement of thickness of alveolar
      bone proper were performed on the interradicular septum of the first molar on the
      sagittal surface. The trabecular bone volume and trabecular number of the OVX
      group were significantly lower than those of the baseline and Sham groups. All of
      the bone resorptive and formative parameters of the OVX group were significantly
      higher (about one-and-a-half times) than those of the Sham group. Several
      osteoclasts were seen lining the irregular, eroded surface facing the bone marrow
      in the OVX group. Furthermore, the OVX group tended to have low microtrabecular
      stiffness and showed significantly thinner distal alveolar bone proper than in
      the baseline and Sham groups. In summary, estrogen deficiency caused osteoporotic
      changes and thin alveolar bone proper in the interradicular septum of rat first
      molar. This phenomenon might accelerate destruction of alveolar bone and tooth
      loss, especially in elderly women affected by periodontal disease.

PMID- 12009187
TI  - Development of an in vitro microassay for glucose quantification in submicrolitre
      volumes of biological fluid.
AB  - Glucose quantification in serum or plasma is traditionally based on a
      colourimetric enzymatic assay using commercially available assay kits. Sample
      volumes of blood or serum are usually in the range of a few microlitres to a few
      millilitres. However, for biological fluids such as gingival crevicular fluid
      (GCF), which can only be sampled in submicrolitre volumes, such assays have
      proven unsuitable. The aim of this study was to develop a reliable and
      reproducible assay for quantifying glucose in submicrolitre samples of GCF. The
      assay involved modification of a commercially available kit for glucose
      quantification. Test solutions of (i) serum and (ii) serum with added glucose at
      known concentrations (range 50-400 mg/dl) were prepared to simulate GCF and GCF
      enriched with glucose, respectively. Submicrolitre volumes (range 0.2 microl to
      0.8 microl) of the test solutions were added to the reagent solution (200 microl)
      using a Hamilton syringe. The reaction was performed under standard conditions of
      time and temperature. The colour change was assayed spectrophotometrically at 492
      nm. The results showed that this microassay is sufficiently sensitive to detect
      50 mg/dl glucose in 0.2 microl of sample and indicate that the accuracy and
      sensitivity of this assay make it suitable for glucose quantification in
      submicrolitre volumes of GCF, particularly relevant to investigations of the
      relationship between diabetes mellitus and chronic inflammatory periodontal
      disease. In vivo evaluation of this novel microassay was performed using GCF
      samples taken from periodontally healthy and chronic periodontitis patients.
      Using non-parametric analysis, the results showed that the assay detected
      statistically significant differences in glucose concentrations between the two
      patient groups (p < 0.05). Higher glucose levels were detected at the
      periodontally diseased sites. For each patient, the GCF-glucose: blood-glucose
      ratio was calculated. The results show that this ratio was higher in the
      periodontitis group (1: 2) when compared to the healthy group (1: 9). In
      conclusion, the results of this investigation have shown that this microassay can
      quantify glucose in GCF and that GCF-glucose levels are higher at periodontitis
      sites.

PMID- 12009188
TI  - Parotid salivary S-IgA antibodies during experimental gingivitis in smokers and
      non-smokers.
AB  - Persons who smoke display a less pronounced increase of gingival bleeding in the
      experimental gingivitis model as compared with non-smokers. The aim of the
      present study was to investigate whether this could partly be explained by
      differences in levels of parotid total secretory IgA (S-IgA) or parotid S-IgA
      reactive with selected oral microorganisms. Parotid saliva samples were obtained
      from 11 smoking and 14 non-smoking volunteers, at baseline, after 5 and 14 days
      of full mouth experimental gingivitis. Output levels of total S-IgA and of
      specific S-IgA reactive with cell extracts from Actinobacillus
      actinomycetemcomitans, Actinomyces naeslundii, Campylobacter rectus,
      Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia,
      Prevotella nigrescens, Peptostreptococcus micros, Streptococcus gordonii and
      Streptococcus mutans were determined in the samples by means of ELISA. Smokers
      and non-smokers were found to have similar output levels (microg/min) of total S
      IgA, and the values did not significantly change during the experimental
      gingivitis trial. Parotid salivary outputs (units/min) of the bacteria-specific S
      IgA at baseline and at days 5 and 14, were not different between smokers and non
      smokers; no changes were observed during the experimental gingivitis trial. The
      present observations indicate that total S-IgA and bacteria-specific S-IgA in
      saliva are not main factors that can explain the less pronounced increase of
      gingival bleeding in the experimental gingivitis model in smokers as compared
      with non-smokers.

PMID- 12009189
TI  - Peri-implant bone regeneration using recombinant human bone morphogenetic protein
      2 in a canine model: a dose-response study.
AB  - The objective of this study was to evaluate the effect of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) dose on alveolar ridge augmentation and dental
      implant osseointegration. Bilateral, 5 mm supraalveolar, peri-implant defects
      were surgically created in 6 beagle dogs. rhBMP-2 (0.05, 0.1 or 0.2 mg/ml) in an
      absorbable collagen sponge (ACS) carrier was molded around the fixtures and
      wounds were closed. Treatment variations were alternated between animals
      (incomplete block design). Animals were sacrificed at week 8 postsurgery. Nine of
      twelve jaw quadrants healed uneventfully. Two jaw quadrants exhibited wound
      failure by week 4 and one by week 8 postsurgery. Radiographic bone regeneration
      was observed in defects without wound failure from week 4 postsurgery.
      Radiolucent voids of variable size and shape were observed and regressed over
      time. In weeks 6 through 8, there was an apparent increase in bone density and
      trabecular structure, while bone height and volume decreased. Histometric
      analysis revealed limited differences in bone regeneration between experimental
      conditions. Bone regeneration area averaged (+/- SD) 1.0 +/- 0.5, 3.5 +/- 1.4 and
      2.3 +/- 0.4 mm2 for the 0.05, 0.1 and 0.2 mg/ml dose, respectively. There were no
      significant differences in osseointegration. Osseointegration in newly formed
      bone averaged 19 +/- 4%, 18 +/- 10% and 21 +/- 6% for the 0.05, 0.1 and 0.2 mg/ml
      rhBMP-2 sites, respectively. Collectively, the data suggest that there are no
      dramatic differences in bone induction and osseointegration within the selected
      dose and observation interval.

PMID- 12009190
TI  - Influence of soil organic matter on the leaching of polycyclic aromatic
      hydrocarbons in soil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are one of the main classes of
      contaminants in the terrestrial environment. Aside from total organic carbon, the
      ratio among the different organic matter fractions [dissolved organic matter,
      fulvic acid (FA), humic acid (HA) and humin] can also affect the mobility of
      these hydrocarbons in soils. In this study the effect of the whole organic carbon
      pool has been compared with that of HA and FA on the translocation of four PAHs
      (biphenyl, fluorene, phenanthrene and pyrene) in soil columns. Oxidized and
      untreated soil columns with and without HA or FA, were prepared, spilled with
      hydrocarbons and leached with a 0.01 M CaCl2 solution. The influence of HA and FA
      on PAH translocation was investigated through determinations of the PAH contents
      and total organic carbon (TOC) in the layers of the columns. All molecules were
      moved vertically by the percolating solutions, their concentrations decreasing
      with depths. The nonoxidized soil tended to retain more PAHs (96%) than the
      oxidized one (60%), confirming that organic matter plays an important role in
      controlling PAH leaching. The whole organic matter pool reduced the translocation
      of pollutants downward the profile. The addition of HA enhanced this behaviour by
      increasing the PAH retention in the top layers (7.55 mg and 4.00 mg in the top
      two layers, respectively) while FA increased their mobility (only 2.30 and 2.90
      mg of PAHs were found in the top layers) and favoured leaching. In fact, in the
      presence of HA alone, the higher amounts of PAHs retained at the surface and the
      good correlation (r2=0.936) between TOC and hydrocarbon distribution can be
      attributed to a parallel distribution of PAHs and HA, while in the presence of
      FA, the higher mobility of PAHs can be attributed to the high mobility of the
      humic material, as expected by its extensive hydrophilic characteristics.

PMID- 12009191
TI  - Assessment of the rhizosphere competency and pentachlorophenol-metabolizing
      activity of a pesticide-degrading strain of Trichoderma harzianum introduced into
      the root zone of corn seedlings.
AB  - To develop a dependable approach to introduce laboratory selected, pesticide
      degrading microorganisms into soil environments for the purpose of in situ
      bioremediation, we tested the possibility of utilizing plant rhizospheres as the
      vehicle. We first established the rhizosphere competency of a strain of the soil
      fungus Trichoderma harzianum, a biocontrol species well studied by plant
      pathologists to colonize plant rhizosphere in many parts of the world. The strain
      we chose, T.h.2023 is resistant to many fungicides, and it has been shown to
      metabolize several pesticides. Second, we found that it readily metabolized
      pentachlorophenol (PCP), which is quickly and stochiometrically converted to
      pentachloroanisole (PCA) in liquid culture. Taking advantage of this specific
      feature, we have developed a sensitive metabolic marker approach that allowed us
      to monitor for the continuous presence and activity of this fungal strain in the
      corn rhizosphere soil in situ over time.

PMID- 12009192
TI  - Persistence and runoff losses of 3 herbicides and chlorpyrifos from a corn field
      in the Lake Balaton watershed of Hungary.
AB  - Corn is intensively cultivated in western Hungary in the basin of Lake Balaton,
      one of the most important water resources in eastern Europe. Pesticide runoff was
      measured in 1996 and 1997 from a typical corn field near Zalaegerszeg, Hungary,
      which drains into the Zala River, an important water source of Lake Balaton.
      Three herbicides, namely atrazine, acetochlor, and propizochlor, and the
      insecticide chlorpyrifos were applied to bare soil in a field with 5% slope and
      soil and runoff water pesticide concentrations were monitored. In 1997, a
      rainfall-runoff simulation experiment was conducted on a small sub-plot in order
      to measure pesticide runoff under reasonable worst-case conditions. Under natural
      rainfall almost all losses occurred in a large runoff event in 1996 one month
      after application in which 3% of atrazine and 1% of acetochlor was transported
      off the field. Propizochlor and chlorpyrifos losses in the same event were much
      lower: 0.2% and <0.01%, respectively, because of these chemicals' shorter
      persistence times in near-surface soil. The rainfall simulation produced only
      trace amounts of losses even though 4.1 cm was applied in 2 hours; the soil was
      extremely dry and only 0.2 cm runoff occurred containing less than 0.01% of all
      chemicals applied. The results suggest that intensive use of corn herbicides,
      which have been found to result in widespread contamination of water resources
      elsewhere, may be expected to have the same impact in the Balaton watershed
      depending on the amounts and intensities used in the basin.

PMID- 12009193
TI  - On-line solid-phase extraction and fluorescence detection of selected endocrine
      disrupting chemicals in water by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was developed to analyse
      selected endocrine disrupting chemicals in water by using automated on-line solid
      phase extraction with a fluorescence detector. The excitation and emission
      wavelengths of the fluorescence detector were 230 nm and 290 nm, respectively.
      The selected endocrine disrupting chemicals include hormone steroids such as
      estradiol (E2), estriol (E3), ethynylestradiol (EE2), and ethynylestradiol 3
      methyl ether (MeEE2) as well as nonylphenols (NP), octylphenols (OP), POE(1-2)
      nonyl phenol (NPE) and bisphenol A (BP). Three types of on-line cartridges (C18,
      PLRP-s and PRP-1) were tested to pre-concentrate the endocrine disruptors in
      deionised water. It was found that the recoveries of these chemicals at 1
      microg/L were close to 100% except for 4-octyl phenol and 4-n-nonyl phenol, which
      had recoveries of about 40% to 80%. The two polymer cartridges (PLRP-s and PRP-1)
      gave higher recoveries than the C18 cartridges. The addition of methanol at 5% to
      10% in water significantly improved the recovery of 4-octyl phenol and 4-n-nonyl
      phenol. The addition of methanol also led to an improvement in the recovery with
      C18 cartridges. With the addition of methanol in water samples, these three types
      of cartridges gave similar recoveries for the chemicals. The detection limits of
      this method ranged from 20 ng/L to 50 ng/L. A river water sample spiked with
      these chemicals was analysed using the above method and we found no interference
      with the peaks of the selected endocrine disrupting chemicals. The recoveries for
      these chemicals were more than 92% except for 4-NP with a recovery of 61%. This
      relatively simple method is useful for laboratory studies on the environmental
      fate of these endocrine disrupting chemicals in water.

PMID- 12009194
TI  - Release characteristics of encapsulated formulations incorporating plant growth
      factors.
AB  - The release characteristics of encapsulated formulations containing a combination
      of plant growth factors (PGF)--plant hormones (IBA, paclobutrazol), nutrients
      (fertilizers, microelements), and fungicide (prochloraz)--were studied. The
      formulations were prepared by encapsulating the active ingredients in a
      polyethylene matrix and, in some cases, subsequently coating the product with
      polyurethane. Dissolution experiments were carried out with both coated and non
      coated formulations to determine the sustained release patterns of the active
      ingredients. The PGF controlled-release systems obtained have been shown to
      promote development of root systems, vegetative growth, and reproductive
      development in cuttings, potted plants, or garden plants of various plant
      species. These beneficial effects are attributable to the lasting and balanced
      PGF availability provided by these systems.

PMID- 12009195
TI  - Determination of pesticides and chronic test with Daphnia magna for rainwater
      samples.
AB  - Pesticides contained in rainwater were investigated in June and July 2001 in
      Yokohama. Although there were few farms and rice paddies near the sampling point,
      insecticides (fenitrothion and dichlorvos) and fungicides (chlorothalonil and
      futhalide) were detected by GC-MS and GC-FPD analysis. The maximum concentrations
      of dichlorvos and fenitrothion were 0.22 microg/L and 0.15 microg/L,
      respectively. Chronic tests with Daphnia magna were then conducted on two
      rainwater samples. Test solutions for these chronic tests were prepared by solid
      phase extraction. In the case of the rainwater sampled on 25 July, the survival
      rate of D. magna was 100% after 21 days and no differences were found between the
      control and sample with regard to the average total number of live offspring
      produced per parent animal. However, a similar test with rainwater sampled on 14
      15 June showed a marked toxic effect, since all the test animals were dead within
      2 days. It is concluded that rainwater containing pesticides is an important
      ecological factor for freshwater plankton.

PMID- 12009196
TI  - Comparison of media and a liquid detergent extraction step on bacterial recovery
      from animal feeds.
AB  - The objective of this study was to evaluate the recovery of Tryptic soy agar
      (TSA) or low nutrient R2 bacterial populations from fresh feeds and animal feeds
      held in long-term cold storage after extraction with a detergent-based solution
      combined with repeated centrifugation. Repeated centrifugation after exposure to
      a detergent-based solution resulted in recoveries generally no more than 10% of
      the microbial population in the original feed. Feed R2A populations were
      significantly correlated (P<0.01) with TSA populations enumerated from the feed
      and feed extracts, as well as R2A populations from feed extracts. Similarly, TSA
      bacterial populations from feed were significantly correlated with TSA
      populations from extracts.

PMID- 12009197
TI  - Bacterial responses to temperature during aeration of pig slurry.
AB  - The temperature effect on total anaerobic and aerobic bacterial growth in pig
      slurry was studied using low level batch aeration treatments. Five bioreactors
      were built using Plexiglas tubes to perform five temperature treatments (5
      degrees C, 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C). An
      airflow rate of 0.129 L/min/L manure was used to aerate manure contained in all
      reactors. Data showed that temperature had a profound impact on the aerobic
      counts in pig slurry during the aeration process. When the temperature increased
      from 15 degrees C to 25 degrees C, the average oxidation-reduction potential
      decreased from +40 mV to -60 mV, accompanied by a 75% reduction of aerobic
      bacteria in the manure. At 25 degrees C, the anaerobic counts were consistently
      higher than aerobic counts for most of days. A quadratic relationship was
      observed between the aerobic counts and the oxidation-reduction potential with a
      correlation coefficient of 0.8374. To reduce odor generation potential, the
      oxidation-reduction potential in the manure should be maintained at +35 mV or
      higher.

PMID- 12009198
TI  - Promising new technology for managing diamondback moth (Lepidoptera: Plutellidae)
      in cabbage with pheromone.
AB  - Experiments were conducted in plantings of cabbage in spring 1999 and 2000 to
      evaluate a novel, new matrix system for delivering sex pheromone to suppress
      sexual communication by diamondback moth, Plutella xylostella (L.). The liquid,
      viscous, slow-release formulation contained a combination of diamondback moth
      pheromone, a blend of Z-11-hexadecenyl acetate, 27%:Z-11-hexadecen-1-ol, 1%:Z-11
      tetradecen-1-ol, 9%:Z-11-hexadecenal, 63%, and the insecticide permethrin (0.16%
      and 6% w/w of total formulated material, respectively). Field trapping
      experiments showed that the lure-toxicant combination was highly attractive to
      male moths for at least four weeks using as little as a 0.05 g droplet of
      formulated material per trap; and the permethrin insecticide had no apparent
      influence on response of moths to lure baited traps. Small field plots of cabbage
      were treated with the lure-toxicant-matrix combination using droplets of 0.44 and
      0.05 g each applied to cabbage in a grid pattern at densities ranging from 990 to
      4396 droplets/ha to evaluate the potential for disrupting sexual communication of
      diamondback moth. There was no significant difference in the level of suppression
      of sexual communication of diamondback moth, as measured by captures of males in
      pheromone-baited traps located in the treated plots, versus moths captured in
      untreated control plots, among the treatments regardless of droplet size (0.05 or
      0.44 g) or number of droplets applied per ha. Plots treated with the smallest
      droplet size (0.05 g) and with the fewest number of droplets per ha (990)
      suppressed captures of male diamondback moths > 90% for up to 3 weeks post
      treatment. Although laboratory assays showed that the lure-toxicant combination
      was 100% effective at killing the diamondback moth, the mode of action in the
      field trials was not determined. The results indicate that the liquid, viscous,
      slow release formulation containing diamondback moth pheromone could be used to
      effectively suppress sexual communication of this pest in cabbage and other
      crucifers, although as many as three applications probably would be required for
      suppression over an entire growing season.

PMID- 12009199
TI  - Quantification of plasma and intracellular levels of the HIV protease inhibitor
      ritonavir by competitive ELISA.
AB  - The HIV protease inhibitor ritonavir (Norvir; ABT-578), currently used in
      combination with nucleoside analogs and other protease inhibitors in anti-HIV
      therapy, has previously been quantified by an HPLC procedure. Here, we report the
      first convenient one-step competitive ELISA for measuring plasma and
      intracellular ritonavir in HIV patients. Anti-ritonavir antibody was raised in
      rabbits using ritonavir-KLH conjugate as immunogen, and the enzymatic tracer was
      prepared by coupling the drug to acetylcholine esterase. Samples for analysis
      were first extracted with methanol. Bound/free separation was achieved in a
      microtiter plate previously coated with anti rabbit IgG monoclonal antibody.
      Fifty percent inhibition was observed at 1 ng/ml ritonavir and the method
      accurately and specifically detected as little as 3-4 ng/ml of plasma ritonavir
      as well as intracellular drug in the peripheral blood mononuclear cells of
      patients undergoing ritonavir therapy. Within-run and day to day coefficients of
      variation were below 10% and the drugs currently used in HIV therapy did not
      interfere with the test. The ELISA was applied to the measurement of plasma
      ritonavir and to the determination of the extracellular/intracellular drug level
      ratios in HIV patients receiving long-term multidrug therapy.

PMID- 12009200
TI  - Th1/Th2 biasing effects of vaccination in cattle as determined by real-time PCR.
AB  - Real-time polymerase chain reaction (PCR) is now becoming an accepted tool for
      measuring gene expression at the transcriptional level. In this study, a direct
      comparison between real-time PCR, enzyme-linked immunosorbent assay (ELISA) and
      enzyme-linked immunosorbent spot (ELISPOT) assay was performed. When interferon
      gamma (IFN-gamma) gene expression was assessed, both ELISA and ELISPOT data
      strongly correlated to results obtained by real-time PCR. Real-time PCR was
      subsequently used to measure bovine IFN-gamma (bIFN-gamma) and bovine interleukin
      4 (bIL-4) gene expression by antigen stimulated peripheral blood mononuclear
      cells (PBMC), isolated from bovine herpesvirus-1 (BHV-1) infected animals. BHV-1
      infected animals were either non-vaccinated or vaccinated using one of two
      adjuvants prior to infection. With non-vaccinated infected animals, a Th1 bias
      occurred, based on IFN-gamma expression exceeding IL-4 expression. The level of
      cytokine expression, and the IFN-gamma/IL-4 ratio could be significantly
      affected, depending on the manner in which animals were vaccinated.

PMID- 12009201
TI  - A comparison of ELISA and flow microsphere-based assays for quantification of
      immunoglobulins.
AB  - An automated microsphere-based flow cytometric assay (FlowMetrix system) was
      compared with a conventional enzyme-linked immunosorbent assay (ELISA) for
      quantifying Ig classes in serum and stool samples. The reproducibility of the
      process of coupling capture antibodies to microspheres was tested. The use of
      independently coupled microspheres did not increase the variation of assay
      results relative to using the same bead set in repeated assays. However, it is
      necessary to ensure quality control of the coupling process since slight
      variations in the coupling procedures can profoundly affect the density of
      capture reagents coupled to the microspheres and consequently adversely affect
      assay precision. Although the ELISA was more sensitive and did not have the
      problems with instrument performance encountered with the FlowMetrix assay, the
      latter was more reproducible, had a greater dynamic range of measurement, and
      took considerably less preparation time than the ELISA. Greater reproducibility
      is especially important for measurement of fecal Ig, which is typically highly
      variable. Thus, in addition to its multi-analyte capability, the FlowMetrix assay
      system has definite advantages over a conventional ELISA. Mechanical problems
      such as microspheres settling to the bottom of wells during analysis by an
      automated plate reader will likely be overcome, and sensitivity improved as this
      technology develops.

PMID- 12009202
TI  - Rapid and sensitive detection of biological warfare agents using time-resolved
      fluorescence assays.
AB  - We have achieved sensitive, rapid and reproducible detection of three biological
      threat agents in a variety of biological and environmental matrices using the
      DELFIA time-resolved fluorometry (TRF) assay system (Perkin-Elmer Life Sciences,
      Akron, OH). Existing ELISA assays for the detection of Francisella tularensis,
      Clostridium botulinum A/B neurotoxin (BotNT A/B), and Staphylococcus aureus
      enterotoxin B (SEB) were converted to TRF assays. They use 100 microl of positive
      control or unknown per test well and require just over 2 h to run. Fluorescent
      signal read time is a fraction of a second per well. The assay format consists of
      a capture ELISA utilizing a biotinylated capture antibody, prebound to a
      streptavidin-coated 96-well plate and a lanthanide (Europium, Eu3+)-labeled
      detector antibody. The bound Eu-labeled detector antibody produces a fluorescent
      signal upon the addition of an enhancement solution. The signal results from the
      dissociation of the Europium from the antibody, creating a micelle, thus
      amplifying the signal nearly one million-fold. Sensitivities achieved by these
      assays were between 4 and 20 pg/ml in buffer. Additionally, we have tested this
      system in different matrices such as serum, urine, dirt, and sewage.
      Concentration curves generated from standard solutions produced a wide linear
      range making serial dilutions of unknown samples unnecessary. DELFIA TRF assays
      are significantly better in terms of sensitivity, linear range, and run time than
      standard capture ELISAs and should facilitate early detection of potential
      biological warfare agents in clinical and environmental samples.

PMID- 12009203
TI  - An ELISA for SGP28/CRISP-3, a cysteine-rich secretory protein in human
      neutrophils, plasma, and exocrine secretions.
AB  - Specific granule protein of 28 kDa (SGP28), also termed cysteine-rich secretory
      protein 3 (CRISP-3), is a glycoprotein that belongs to a family of cysteine-rich
      secretory proteins (CRISPs). SGP28 was originally discovered in human
      neutrophils, but transcripts are widely distributed in exocrine glands (salivary
      glands, pancreas, and prostate) and also found at lower levels in epididymis,
      ovary, thymus, and colon. The function of SGP28/CRISP-3 is not yet known.
      Similarities to pathogenesis-related proteins in plants and the expression in
      neutrophils and exocrine glands suggest that SGP28/CRISP-3 may play a role in
      innate host defense. We describe here the production of a recombinant, C
      terminally truncated form of CRISP-3 (rCRISP-3Delta) and the generation of
      polyclonal antibodies against rCRISP-3Delta that are useful in immunoblotting and
      immunocytochemistry. We present a specific, accurate, and reproducible enzyme
      linked immunosorbant assay (ELISA) for the measurement of CRISP-3 with a
      detection limit of 2 ng/ml. We further demonstrate the presence of CRISP-3
      protein in human plasma (6.3 microg/ml), saliva (21.8 microg/ml), seminal plasma
      (11.2 microg/ml), and sweat (0.15 microg/ml), and describe the coexistence of two
      different molecular weight forms of CRISP-3, representing an N-glycosylated and a
      non-glycosylated form of the mature protein.

PMID- 12009204
TI  - Enhanced pepsin digestion: a novel process for purifying antibody F(ab')(2)
      fragments in high yield from serum.
AB  - Enzyme-cleaved antibodies are used widely for the treatment of envenoming. Such
      products should comprise only 'highly pure' immunoglobulin fragments since Fc or
      other contaminating protein fragments or their aggregates may lead to side
      effects. The digestion of ovine antiserum and its purified IgG were investigated
      using pepsin and trypsin. Trypsin was effective at digesting purified IgG but
      unsuitable for the direct digestion of serum. In contrast, pepsin was highly
      effective at digesting all unwanted serum components to low molecular weight (<
      or =13 kDa) fragments while leaving the approximately 100-kDa F(ab')(2) intact.
      The optimum pH for pepsin digestion was between 3.25 and 3.50. The effects of
      salt concentration and pH on the digestion products were investigated by size
      exclusion chromatography under various conditions, which revealed a pH-dependent
      aggregation of some of the low molecular weight Fc and non-IgG fragments. These
      high molecular weight aggregates were not shown by SDS-PAGE. Unwanted low
      molecular weight fragments could be removed simply by diafiltration with a 30-kDa
      nominal molecular weight cutoff membrane and piperazine buffer (containing 150 mM
      NaCl, pH 6), leaving an F(ab')(2) solution contaminated only with some pepsin and
      a small amount of the aggregated low molecular weight fragments. These highly
      acidic contaminants were then removed easily using an anion exchange column and
      the F(ab')(2) produced following a subsequent concentration step was essentially
      free from pepsin and aggregates with a purity of over 96% and a yield of 19.3 g
      F(ab')(2)/l serum. This novel, high yield method for processing serum to highly
      pure F(ab')(2) avoids salt precipitation and centrifugation and should be
      suitable for large-scale production.

PMID- 12009205
TI  - Application of a modified version of Habeeb's trinitrophenylation method for the
      characterization of hapten-protein conjugates in a reversed micellar medium.
AB  - We describe here a protocol for determining the epitope density of hapten-carrier
      conjugates at the nanomolar level. Conjugates of bovine serum albumin (BSA) and
      hen egg albumin (OVA) were prepared with two model haptens: 4-acetyl benzoic acid
      (ABA) as a chromophoric carboxylic hapten and cholesterol hemisuccinate (Chol HS)
      as a carboxylic derivative of a nonchromophoric hydroxylated hapten. Small-scale
      but valuable haptenization of carriers was achieved (approximately 4.3 nmol with
      an input molar ratio of hapten to carrier within the range from 50:1 to 100:1)
      that proved yet compatible with immunogenicity and antibody detection. We used a
      modified version of the amide bond-generating mixed anhydride method of Erlanger
      performed in a reversed micellar medium. Microsample aliquots of the coupling
      reaction (carriers plus activated haptens) or control experiment (carriers plus
      nonactivated haptens) mixtures were directly subjected to trinitrophenylation in
      the reversed micellar medium. The results for carrier substitution were strongly
      correlated (r2=0.94; n=12) with those obtained by other methods such as UV
      analysis (for ABA) and chromatographic determination (for Chol HS). This method
      was found directly applicable to other hapten-carrier conjugates coupled by the
      same procedure, provided that the haptens do not absorb at about 335 and 420 nm
      (absorption peaks of trinitrophenyl groups). With this simple, rapid,
      reproducible and low-cost analysis method, the separation of uncoupled hapten and
      conjugate is unnecessary. This facilitates the optimization of reaction
      conditions. Finally, using this procedure, kinetic studies of conjugate formation
      can be carried out in a very simple manner.

PMID- 12009206
TI  - Comparative analysis of methods for collection and measurement of cytokines and
      immunoglobulins in cervical and vaginal secretions of HIV and HPV infected women.
AB  - The goal of these studies was to distinguish which of two techniques
      [cervicovaginal lavage (CVL) and cervical wick (SS)] is the optimal collection
      method for the measurement of the local immunological response in human
      papillomavirus (HPV) and HIV infected women. The following parameters were
      measured in 24 paired samples from 15 women (9 HIV+, 6 HIV-): total protein,
      immunoglobulin levels, HPV-specific antibodies, and Th1-Th2 cytokines. In
      addition, relative mRNA levels from CVL cell pellets were compared to protein
      levels from CVL supernatants. The total protein (2-fold) and IgG concentration
      (10-fold) are higher in the SS samples, were reproducible (%CV<3) and these
      levels correlated (P<0.0001) with their paired CVL sample. Type-specific HPV-L1
      IgG and IgA antibodies were detected in CVL and SS (r>0.28, P<0.008) with
      excellent reproducibility (CV<3.0%). However, SS (%CV>18) failed to yield
      reproducible results for the cytokine assays as compared to the CVL (%CV<5.0).
      Furthermore, no correlations were found between relative mRNA levels from CVL
      cell pellet and cytokine protein levels in CVL supernatants. The CVL sample's
      superior reproducibility in the cytokine assays makes this the better collection
      method. In addition, cytokine protein level's failure to correlate with mRNA
      suggests tight regulation of cytokine genes or production from a different cell
      population.

PMID- 12009207
TI  - Selection by phage display of llama conventional V(H) fragments with heavy chain
      antibody V(H)H properties.
AB  - A llama single domain antibody (dAb) library designed and constructed to contain
      only heavy chain antibody variable domains (V(H)Hs) also contained a substantial
      number of typical conventional antibody heavy chain variable sequences (V(H)s).
      Panning the library against two carbohydrate-specific antibodies yielded anti
      idiotypic dAbs and enriched solely for sequences from the V(H) subpopulation of
      the library. The conventional antibody origin of these V(H)s was confirmed by
      using oligonucleotide probes, specific for the enriched V(H)s, to identify the
      parental sequences in the message employed in library construction. Surprisingly,
      these V(H) dAbs, which are produced in high yield in Escherichia coli, are highly
      soluble, have excellent temperature stability profiles and do not display any
      aggregation tendencies. The very close similarity of these molecules to human
      V(H)s makes them potentially very useful as therapeutic dAbs.

PMID- 12009208
TI  - Stabilization of soluble, low-affinity HLA-DM/HLA-DR1 complexes by leucine
      zippers.
AB  - The ectodomains of interacting membrane-bound proteins, when expressed as
      recombinant soluble molecules, often have low affinities for each other,
      hampering studies of their interaction. We reasoned that stabilization of
      unstable protein-protein complexes should aid our understanding of the structural
      and functional consequences of complex formation. Here, we have used fusion with
      leucine zipper (LZ) domains to stabilize a complex formed between the class II
      major histocompatibility complex (MHC-II) protein, HLA-DR1 (which binds peptides
      for presentation to CD4+ T cells) and HLA-DM (which catalyzes peptide exchange of
      MHC-II molecules). To this end, the DM beta chain ectodomains were fused to
      acidic LZ domains (AcidP1 or Fos); similarly, the DR1 beta chain ectodomains were
      fused to basic LZ domains (BaseP1 or Jun). We expressed LZ-modified soluble DM or
      DR1 alphabeta dimers, or both, in insect cells and purified the secreted sDM
      AcidP1 and sDR1-BaseP1 molecules as well as the complex. LZ modification greatly
      enhanced DM-catalyzed peptide binding to DR1 compared to unmodified soluble DM
      and DR1. We readily detected LZ-modified DM/DR complexes on native PAGE gels and
      by coimmunoprecipitation. Thus, fusion with artificial LZ domains can stabilize
      unstable protein-protein complexes for biochemical and structural studies of
      interactions within the complex.

PMID- 12009209
TI  - Progressive epitope-blocked panning of a phage library for isolation of human RSV
      antibodies.
AB  - Epitope-blocked panning is an approach to mining antigen-specific diversity from
      phage display antibody libraries. Previously, we developed and used this method
      to recover a neutralizing antibody to respiratory syncytial virus (RSV) by
      blocking a dominant response to a nonneutralizing epitope on a recombinant
      derivative of the viral F antigen. We have extended this approach to the blocking
      of multiple epitopes simultaneously, which led to the recovery of new antibodies
      of different specificity, including one new neutralizing activity. A phage
      display Fab library was selected on recombinant F antigen in the presence of
      three representative antibodies recovered in the unblocked and subsequent single
      blocked panning procedures. Restriction endonuclease fingerprinting of 13 F+
      clones revealed seven unique Fabs. DNA sequence analysis of five of these clones
      revealed five new light chains in combination with different heavy chains, three
      of which were very similar or identical to Fabs previously isolated from this
      library. The blocking antibodies did not compete with the new Fabs, demonstrating
      effective masking of their binding sites in the panning procedure. Conversely,
      these Fabs did show variable inhibition of two of the blocking antibodies
      suggesting a close proximity or interdependence of their epitopes. One of the
      antibodies did inhibit virus infection, albeit with modest potency. These results
      demonstrate that epitope-blocked panning is a self-progressing approach to
      retrieving diverse antibodies from phage libraries.

PMID- 12009210
TI  - Expression of full-length immunoglobulins in Escherichia coli: rapid and
      efficient production of aglycosylated antibodies.
AB  - Many research and clinical applications require large quantities of full-length
      antibodies with long circulating half-lives, and production of these complex
      multi-subunit proteins has in the past been restricted to eukaryotic hosts. In
      this report, we demonstrate that efficient secretion of heavy and light chains in
      a favorable ratio leads to the high-level expression and assembly of full-length
      IgGs in the Escherichia coli periplasm. The technology described offers a rapid,
      generally applicable and potentially inexpensive method for the production of
      full-length therapeutic antibodies, as verified by the expression of several
      humanized IgGs. One E. coli-derived antibody in particular, anti-tissue factor
      IgG1, has been thoroughly evaluated and has all of the expected properties of an
      aglycosylated antibody, including tight binding to antigen and the neonatal
      receptor. As predicted, the protein lacks binding to C1q and the FcgammaRI
      receptor, making it an ideal candidate for research purposes and therapeutic
      indications where effector functions are either not required or are actually
      detrimental. In addition, a limited chimpanzee study suggests that the E. coli
      derived IgG1 retains the long circulating half-life of mammalian cell-derived
      antibodies.

PMID- 12009211
TI  - Characterization of anti-cyclin E single-chain Fv antibodies and intrabodies in
      breast cancer cells: enhanced intracellular stability of novel sFv-F(c)
      intrabodies.
AB  - Cyclin E is a critical cell cycle protein in the regulated progression of normal
      cells to replicate their DNA. Ectopic overexpression of cyclin E results in
      accelerated G(1) progression, chromosome instability, and a reduced requirement
      for growth factors. Dysregulated cyclin E expression is found in nearly all
      breast cancers examined. Toward the goal of developing a system to block cyclin E
      function in normal and breast cancer cells, we have developed anti-cyclin E
      single-chain antibodies (sFvs) for use as intrabodies. We have cloned the
      variable region genes from two hybridoma cell lines that produce anti-human
      cyclin E antibodies, linked them into sFvs, and showed their ability to bind
      cyclin E when expressed as sFv-F(c) fusion proteins. Engineering of the sFvs as
      sFv-F(c) intrabodies resulted in a dramatic increase in the sFv half-life as
      analyzed by pulse-chase and immunofluorescence, and these fusion intrabodies can
      be expressed in the cytosol or retargeted to the nucleus of breast cancer cell
      lines. Stable expression of a nuclear-targeted anti-cyclin E intrabody appears to
      inhibit the growth of the breast cancer cell line SKBR3. This work sets the stage
      for the development of intrabody-based inducible or tissue-specific cyclin E
      knockouts and for identifying cyclin E and its vital cell cycle functions as a
      potential gene therapy target in breast and other cancers.

PMID- 12009212
TI  - Measurement of interferon-gamma by high-throughput fluorometric microvolume assay
      technology system.
AB  - Interferon gamma (IFN-gamma) has various immunoregulatory effects and its
      measurement is widely used for monitoring immune response in many clinical trials
      for cancer vaccines. In this study, we developed a fluorescent-linked
      immunosorbent assay (FLISA) for the measurement of IFN-gamma. The FLISA can
      accurately measure IFN-gamma concentrations and the linear dynamic range of
      standard curve is 15.6-2000 pg/ml (2.1 log range). Because the FLISA needs only a
      small amount of antibodies and there is no washing process, it is able to reduce
      hands-on time and running costs compared with traditional enzyme-linked
      immunosorbent assay (ELISA). The FLISA can be readily performed in both 96- and
      384-well plates, and up to 60 plates can be handled automatically by a robotic
      arm. Measurement of IFN-gamma by fluorometric microvolume assay technology (FMAT)
      may be a high-throughput screening method for a large number of samples.

PMID- 12009214
TI  - Asmund S. Laerdal.

PMID- 12009215
TI  - An analysis of time factors in out-of-hospital cardiac arrest in Osaka
      Prefecture.
AB  - OBJECTIVE: To ascertain important factors in the improvement of out-of-hospital
      cardiac arrest survival rates through analysis of data for Osaka Prefecture with
      the focus on time factors. DESIGN: Prospective cohort study according to the
      Utstein style. SETTING: Osaka Prefecture (population 8,830,000) served by a
      single emergency medical services system. PATIENTS: Consecutive prehospital
      cardiac arrests occurring between May 1998 and April 1999. MAIN OUTCOME MEASURES:
      One-year survival from cardiac arrest, and time factors. RESULT: Of the 5047
      cases of confirmed cardiac arrests, resuscitation was attempted in 4871 subjects.
      Of the 982 cases of cardiac origin and witnessed by bystanders, 31 (3.2%) were
      still alive, and of the 576 cases of non-cardiac origin and witnessed by
      bystanders, ten (1.7%) were still alive at the 1 year follow-up. The median time
      from receipt of the emergency call until ambulance arrival was 5 min and that
      from receipt of the call until the start of cardiopulmonary resuscitation (CPR)
      was 7 min. For the 214 patients for whom defibrillation was attempted, the median
      time from receipt of the call until the first shock was 15 min. The median time
      from receipt of the call until departure of the ambulance from the scene was 16
      min and that until arrival of the ambulance at a hospital was 22 min.
      CONCLUSIONS: This study using the standardized format according to the Utstein
      style clearly elucidates the specific delay of the start of defibrillation by
      paramedics and also indicates the inappropriate rule for this procedure in Japan.

PMID- 12009216
TI  - Characteristics and outcome among patients suffering from in hospital cardiac
      arrest in relation to whether the arrest took place during office hours.
AB  - AIM: To describe the characteristics and outcome among patients suffering from in
      hospital cardiac arrest in relation to whether the arrest took place during
      office hours. PATIENTS: All patients suffering in hospital cardiac arrest in
      Sahlgrenska University hospital in Goteborg, Sweden between 1994 and 1999 in whom
      resuscitative efforts were attempted and for whom the time when the
      cardiopulmonary resuscitation (CPR) team was alerted. METHODS: Prospective
      recording of various factors at resuscitation including the time when the CPR
      team was alerted. Retrospective evaluation via medical records of patients
      previous history and final outcome. RESULTS: Among patients in whom the arrest
      took place during office hours (08:00-16:30 h) the overall survival rate was 49%
      as compared with 26% among the remaining patients (P<0.0001). The corresponding
      figures for patients found in ventricular fibrillation were 66 and 44%
      (P=0.0001), for patients found in asystole 33 and 22% (NS) and for patients found
      in pulseless electrical activity 14 and 3% (NS). When correcting for
      dissimilarities in previous history and factors at resuscitation the adjusted
      odds ratio for patients to be discharged alive who had the arrest during office
      hours was 2.07 (1.40-3.06) as compared with patients who had an arrest outside
      office hours. CONCLUSION: Among patients suffering from in hospital cardiac
      arrest and in whom CPR was attempted those who had the arrest during office hours
      had a survival rate being more than twice that of patients who had the arrest
      during other times of the day and night. These results indicate that the
      preparedness for optimal treatment of in hospital cardiac arrest is of ultimate
      importance for the final outcome and that an increased preparedness during
      evenings and nights might increase survival among patients suffering from in
      hospital cardiac arrest.

PMID- 12009217
TI  - Dispatcher-assisted telephone CPR: a qualitative study exploring how dispatchers
      perceive their experiences.
AB  - OBJECTIVES: To investigate how emergency medical dispatchers (EMDs) perceive
      their experience of identifying suspected cardiac arrests (CA), and offer and
      provide instructions in cardiopulmonary resuscitation via telephone (t-CPR).
      DESIGN: A qualitative method using the phenomenographic design where 10 EMDs were
      approached for semi-structured interviews. MAIN OUTCOME MEASURES: Perception in
      identifying CA, perception in offering t-CPR and perception in providing t-CPR.
      RESULTS: In this analysis, 12 categories and 31 subcategories emerged. The
      categories for perception in identifying CA were; to trust the witness's account,
      to be open-minded and to be organised. The categories for perception in offering
      t-CPR were: to feel prepared to connect with the witness on a mental level by
      being organised, flexible and supportive, to obtain a basis for assessments and
      to be observant for diverse obstacles in a situation. Finally, the categories for
      perception in providing t-CPR were: to feel engaged, to be supportive of the
      witness, to feel secure by recognising response-feedback from the witness, to
      observe external conditions with regard to the locality and technical
      complications, to be composed and adjust to the needs of the situation, to feel
      competent or to feel despair. CONCLUSIONS: By listening in an open-minded way, a
      vast amount of information can be collected. Using criteria-based dispatch (CBD)
      and their own resources, the possibilities and difficulties of the situation are
      analysed. The EMDs believe that they are being an empathic support, relieving the
      witness of the burden of responsibility, and connecting with them mentally to
      enable them to act at the scene. There are EMDs who feel competent and
      experienced in managing these cases, and other EMDs who feel insecure and
      despair. The choice between providing t-CPR and answering incoming calls is
      prioritised differently among EMDs. There is also a broad subjective assessment
      among EMDs of offering t-CPR, especially to persons over 70 years old whom they
      consider incapable of performing CPR. The competence of the EMDs in t-CPR is
      dependent on re-training and a feedback on patient outcome. Witnesses who are
      negative towards acting constitute a common problem. There are witnesses with
      physical impediments or psychologically not susceptible to suggestions. The EMD
      is also dependent on the knowledge and trustworthiness of the witness. Convincing
      answers from witnesses prompt a more secure feeling in the EMDs, just as lack of
      knowledge in the witness has a negative effect on the efforts.

PMID- 12009218
TI  - Endotracheal drug administration during out-of-hospital resuscitation: where are
      the survivors?
AB  - BACKGROUND: Drugs administered endotracheally are effectively absorbed during
      normal spontaneous cardiac activity. However, animal cardiac arrest studies and
      limited clinical investigations do not support either the use of endotracheal
      (ET) drugs in doses currently recommended for adults or the method of direct
      endotracheal instillation. The purpose of this study was to compare the effect of
      intravenous (IV) and ET drug therapy on outcome from out-of-hospital cardiac
      arrest secondary to all cardiac arrest rhythms. DESIGN: Five and one-half year
      retrospective cohort study. SETTING: Municipal, university affiliated hospital.
      PATIENTS: Consecutive patients >18 years of age in nontraumatic out-of-hospital
      cardiac arrest who received advanced cardiac life support (ACLS) medications by
      only the ET or IV route were included. INTERVENTIONS: None. RESULTS: Five hundred
      and ninety-six patients met inclusion criteria (IV drugs=495, ET drugs=101).
      There was no difference between groups in the rate of witnessed arrest and the
      frequency of bystander cardiopulmonary resuscitation (CPR). In the ET drug group,
      a significantly greater number of patients had an initial documented arrest
      rhythm of asystole compared to the IV drug group (56 vs 37%, P=0.01). The rate of
      return of spontaneous circulation (27 vs 15%, P=0.01) and survival to hospital
      admission rate (20 vs 9%, P=0.01) were significantly greater in the IV drug
      group. No patient who received ET drugs survived to hospital discharge compared
      to 5% of those receiving IV drugs (P=0.01). CONCLUSION: For our out-of-hospital
      advanced rescuer system, ET drugs at recommended doses (twice the IV dose)
      injected into an ET tube during cardiac arrest and CPR were of no benefit.

PMID- 12009219
TI  - Towards new models of cardiopulmonary resuscitation teaching: the role of
      practical scenario training on surf lifesavers' perceptions of resuscitation
      efficacy.
AB  - INTRODUCTION: Surf lifesavers in Australia undertake numerous resuscitation
      scenarios in the course of their training and examination. The standard teaching
      and examination strategy is for the scenario to end with return of spontaneous
      circulation (ROSC) and then breathing. This study was performed to assess the
      effect of this training technique on lifesavers' expectation of successful
      resuscitation and to determine the effect of experience on these expectations.
      METHODS: Participants were lifesavers from Surf Life Saving Sydney Northern
      Beaches (SLSSNB). Data was collected by questionnaire. Questionnaires were
      applied to newly qualified lifesavers, a random sample of patrolling lifesavers
      and a strategic group of lifesavers with extensive experience in resuscitation.
      Anticipation of ROSC was recorded on a visual analogue scale (VAS). RESULTS: The
      mean VAS for the expected likelihood of successful resuscitation was 55.0+/-19.2%
      (95% CI: 51.3-58.6%). Published rates of ROSC range from 9 to 36.4%. Nearly 80%
      of our respondents expected better than 36.4% chance of ROSC. There was no
      difference in anticipation of ROSC between the three groups (F=0.41; 2,99df;
      P=0.67). Time since learning cardiopulmonary resuscitation (CPR) did not affect
      the expectancy of ROSC (F=0.92; 5,101df; P=0.47). Similarly, the number of
      resuscitations performed by an individual did not affect anticipation of
      successful outcome (F=0.13; 3,102df; P=0.94). CONCLUSIONS: Surf lifesavers in the
      Sydney Northern Beaches branch have an exaggerated expectation of the chances of
      successful CPR following cardiac arrest. This expectation did not change with
      time since learning CPR or participation in actual resuscitations. New models for
      CPR education need to be investigated.

PMID- 12009220
TI  - Elevations in procalcitonin but not C-reactive protein are associated with
      pneumonia after cardiopulmonary resuscitation.
AB  - A possible diagnostic role of procalcitonin (PCT) as a marker for ventilator
      associated pneumonia (VAP) in patients with an already triggered acute phase
      response after successful cardiopulmonary resuscitation (CPR) was investigated.
      In 28 patients with return of spontaneous circulation (ROSC) after out of
      hospital CPR, measurements of PCT, C-reactive protein (CrP), white blood cell
      count (WBC) and body temperature were compared with the clinical course of the
      patients. In this setting, PCT was the only marker to differentiate between
      patients with and without VAP (median value on day 1, 6.0 vs. 0.5 ng/ml;
      P<0.001). Using a cut off value of 1 ng/ml during the first 7 days after ROSC PCT
      had a sensitivity of 100% and a specificity of 75% to indicate VAP. PCT was
      elevated a median of 2 days earlier than the clinical diagnosis of VAP.
      Elevations in PCT can, therefore, indicate bacterial complications in cardiac
      arrest patients with a non-infectious acute phase response.

PMID- 12009221
TI  - Automated external defibrillators and first responders: a satisfaction survey.
AB  - PRIMARY OBJECTIVE: Automated external defibrillators (AEDs) are used with
      increasing frequency in the United States by first responders (FR) such as police
      officers (PO) or firefighters (FF). However, FR satisfaction with use of AEDs has
      not been investigated. We hypothesized that FR satisfaction is comparable with
      that of paramedics (PA) and that, among those who have defibrillated with AEDs,
      those who have restored a pulse before PA arrival have a higher level of
      satisfaction than those who have not restored a pulse. MATERIALS AND METHODS: A
      21-item questionnaire with closed answers was sent to FR and PA in four
      communities. Each answer was scored 0, 1 or 2. A score between 10 and 16
      correlated with the highest satisfaction level. RESULTS: 276 out of 311
      questionnaires were returned (89%). Two hundred and eleven respondents (35 PA, 70
      FF and 106 PO) had used an AED and 99 FF and PO had restored a pulse before PA
      arrival. The satisfaction level of PO, FF and PA was high as demonstrated by the
      scores: 13.26, 13.07 and 13.39, respectively. Use of AED and pulse restoration
      resulted in higher scores than those of groups who had been trained only and who
      had not restored a pulse. CONCLUSION: FR demonstrated a high level of
      satisfaction with using AEDs, and also had a favorable attitude toward
      implementation of AED use. Restoration of a pulse was clearly a factor
      responsible for a higher satisfaction. This positive attitude should encourage
      further implementation of early defibrillation programs in non-medical first
      responder settings.

PMID- 12009222
TI  - Trials of teaching methods in basic life support (3): comparison of simulated CPR
      performance after first training and at 6 months, with a note on the value of re
      training.
AB  - A randomised controlled trial comparing staged teaching of cardiopulmonary
      resuscitation (CPR) with conventional training provided the additional
      opportunity to investigate skill acquisition and retention in those attending
      conventional CPR classes. All subjects were tested immediately after their first
      instruction period and again at 6-9 months at an unheralded home visit. We were
      able to assess how far performance was related to poor acquisition of skills and
      how far it was related to skill decay. Out of 262 subjects who were randomised to
      receive conventional CPR instruction, 166 were available for home testing at 6-9
      months. An invitation to attend for re-training had been accepted by 39 of them.
      The remaining 127 who attended only a single class comprise the principal study
      group, with additional comparative observations on the smaller re-trained cohort.
      Important failings were observed in the acquisition of skills in all modalities
      tested after the initial instruction. These were particularly marked in skills
      related to ventilation. Immediately after a class, 68% of trainees performed an
      effective check of breathing, but only 33% opened the airway as taught and no
      more than 18% provided an ideal ventilation volume. The technique of chest
      compression was also less than ideal. Although 80% of subjects placed their hands
      in an acceptable position, compression to an adequate depth and an adequate rate
      of compression were achieved by 54 and 63%, respectively. Seventy-eight percent
      demonstrated a careful approach, and 46% remembered to call for help. A carotid
      pulse check was simulated by 61% of trainees. When tested 6-9 months later, skill
      deterioration from this baseline was observed in all modalities tested except for
      the ventilation volume. The skill decay was significant (P<0.05) for the careful
      approach, performing an effective breathing check, the carotid pulse check,
      placing the hands in an acceptable position for chest compression, and
      compressing at an optimal rate. The minority who attended for re-training showed
      a trend to protection against skill decay for seven of the ten variables,
      compared with those who had attended only one training session. This improvement
      was significant for only two of them, but all were relatively small with limited
      practical value. Many who attend conventional CPR classes fail to acquire the
      necessary skills, and the skills that are acquired decline appreciably over the
      subsequent 6-9 months. The value of conventional re-training was modest in this
      study of community volunteers.

PMID- 12009223
TI  - Strain specific differences in a cardio-pulmonary resuscitation rat model.
AB  - An asphyxial cardiac arrest rat model, originally developed for Sprague-Dawley
      rats, was transferred to a Wistar rat model. Several strain specific life support
      adjustments, i.e. ventilator settings, anaesthesia, and drug requirements, were
      necessary to stabilize the model for Wistar rats. Despite these arrangements
      numerous resuscitation related variables appeared different. Three groups were
      evaluated and compared: a temperature monitored Wistar group 1 (n=34), a
      temperature controlled Wistar group 2 (n=26) and a temperature controlled Sprague
      Dawley group 3 (n=7). Overall, Wistar rats seem to have more sensitive cardio
      circulatory system evidenced by a more rapid development of cardiac arrest (164
      vs. 201 s), requiring higher adrenaline/epinephrine doses (10 vs. 5 microg/kg)
      and requiring more time for recovery after resuscitation (i.e. for return of
      blood pressure and blood gases). Without strict temperature control (as in groups
      2+3 rats) group 1 rats went into spontaneous mild to moderate hypothermia during
      the first 24 h after restoration of spontaneous circulation (ROSC). Spontaneous
      hypothermia delayed the development of overall visible CA1 neuronal damage 24-48
      h, but did not prevent it; therefore the model seemed to be suitable for future
      studies. Neuronal damages in the CA1 region in Wistar rats appeared to be more as
      shrunken cell bodies and pyknotic nuclei before resorption took place, whereas in
      Sprague-Dawley rats appeared in the same region.

PMID- 12009224
TI  - Resuscitation from cardiac arrest with adrenaline/epinephrine or vasopressin:
      effects on intestinal mucosal tonometer pCO(2) during the postresuscitation
      period in rats.
AB  - BACKGROUND: The use of vasopressin instead of adrenaline/epinephrine during
      resuscitation improves vital organ perfusion, but the effects on mesenteric
      perfusion following successful resuscitation are not fully evaluated. The present
      study was designed to compare the effects of vasopressin and
      adrenaline/epinephrine, given to rats during resuscitation from ventricular
      fibrillation, on to mesenteric ischaemia, as determined by intestinal mucosal
      tonometer pCO(2) during the postresuscitation period. METHODS AND RESULTS: Male
      Sprague-Dawley rats (n=28) were allocated randomly to receive vasopressin (0.8
      U/kg) or adrenaline/epinephrine (90 microg/kg) after 5 min of ventricular
      fibrillation. Precordial chest compression was initiated 4 min after the start of
      ventricular fibrillation, continued for 4 min, and followed by defibrillation.
      Seven of 14 (vasopressin) and 12 of 14 (adrenaline/epinephrine) rats were
      successfully defibrillated (P=0.10, Fisher's exact test) and observed for 60 min.
      Intestinal mucosal tonometer pCO(2) measurements before cardiac arrest and 15,
      30, and 60 min following return of spontaneous circulation were 47+/-3, 73+/-8,
      63+/-7, and 56+/-6 mmHg in the vasopressin group and 48+/-5, 78+/-7, 67+/-6, and
      62+/-6 mmHg in the adrenaline/epinephrine group (P<0.05 at 60 min between
      vasopressin and adrenaline/epinephrine). Right atrial hemoglobin oxygen
      saturations at these time points were 73+/-5, 51+/-12, 58+/-11, and 63+/-5% in
      the vasopressin group and 76+/-7, 44+/-10, 52+/-10 and 54+/-8% in the
      adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and
      adrenaline/epinephrine). CONCLUSIONS: We conclude that in this rat model the
      administration of vasopressin instead of adrenaline/epinephrine for CPR tends to
      be associated with lower resuscitation success, but less mesenteric ischaemia
      during the postresuscitation period in successfully resuscitated rats.

PMID- 12009225
TI  - Simultaneous sterno-thoracic cardiopulmonary resuscitation improves short-term
      survival rate in canine cardiac arrests.
AB  - We have reported previously that simultaneous sterno-thoracic cardiopulmonary
      resuscitation (SST-CPR) using a device that compresses the sternum and constricts
      the thorax circumferentially during a compression systole that can be achieved
      using standard cardiopulmonary resuscitation (STD-CPR). This study was designed
      to assess whether SST-CPR improves the survival rate of dogs with cardiac arrest
      compared with STD-CPR. Twenty-nine mongrel dogs (19-31 kg) were enrolled in this
      study. After 4 min of ventricular fibrillation induced by an AC current, animals
      were randomized to be resuscitated by either STD-CPR (n=15) or SST-CPR (n=14).
      Defibrillation was attempted 10 min after the induction of cardiac arrest.
      Standard advanced cardiac life support was started if defibrillation was
      unsuccessful. Aortic blood pressure, coronary perfusion pressure, and end tidal
      CO(2) tension were measured during CPR and the post-resuscitation period.
      Survival was determined 12 h after the induction of cardiac arrest. SST-CPR
      resulted in a significantly (P<0.001) higher systolic arterial pressure (91+/-47
      vs 47+/-24 mmHg), diastolic pressure (43+/-24 vs 17+/-10 mmHg), coronary
      perfusion pressure (35+/-25 vs 13+/-9 mmHg), and end tidal CO(2) tension (9+/-4
      vs 3+/-2 mmHg). Two of 15 animals (13%) resuscitated by STD-CPR and seven of 14
      animals (50%) resuscitated by SST-CPR survived for 12 h after cardiac arrest
      (P<0.05). In conclusion, SST-CPR improves the short-term survival rate in canine
      cardiac arrest compared with STD-CPR.

PMID- 12009226
TI  - Survival with an arterial pH of 6.57 following major trauma with exsanguinating
      haemorrhage associated with traumatic amputation.
AB  - We report the survival of a multiply injured patient with exanguinating
      haemorrhage and an arterial pH of 6.5, following a road vehicle crash. The
      previously healthy 38 years old male driver veered off the motorway and collided
      with a tree. The ambulance arrived at the scene 9 min after being called by an
      eyewitness and, following rapid extrication from the wreckage; the patient
      arrived in hospital 27 min later (with a GCS of 6), and was immediately
      intubated. The patient had suffered near-complete amputation of the left leg at
      upper femoral shaft level, along with multiple distal fractures and open wounds.
      He also sustained a head injury and closed displaced fractures of left radius and
      ulna. The patient received 2 l of crystalloids in the pre-hospital phase. Once in
      hospital the haemorrhage was controlled with a pressure dressing and intra-venous
      fluids were kept to a minimum until he was taken promptly to theatre. His initial
      arterial blood sample revealed a pH of 6.57, pCo(2) of 9.18 kPa, a pO(2) of 70.11
      kPa and a base excess of -27.5 mmol l(-1). The co-oximeter Hb was 5.8 g dl(-1).
      Haemorrhage was controlled in theatre where he was transfused a total of 30 U of
      blood, 1 pack of platelets, 12 U of fresh frozen plasma, 3.5 l of crystalloids
      and 1.5 l of colloid. Sodium bicarbonate was administered three times. He
      subsequently remained ventilated in intensive care unit (ICU). Over the following
      week he survived sepsis, disseminated intravascular coagulation and myoglobinuria
      (with transient renal failure) attributable to rhabdomyolysis secondary to muscle
      necrosis. He later underwent diversion colostomy and disarticulating amputation
      of the left femur after several debridements. After 6 weeks on ICU he made an
      excellent recovery will full return of his mental abilities. In this case, the
      serial arterial blood samples obtained were reliable. The lactic acidosis
      observed was the result of profound tissue hypo-perfusion and its rate of
      clearance seems to have greater prognostic value than its peak or initial value.
      Several factors may have contributed to the patient's survival: rapid retrieval
      from the scene; early intubation with excellent subsequent oxygenation (thus
      avoiding the dangerous combination of hypoxia and acidosis with synergistic
      influence on cardiac depression) and limited initial fluid resuscitation in the
      emergency department with prompt surgical intervention and vigorous restoration
      of organ perfusion after surgical haemostasis. Immediate operative haemostasis,
      coupled with restricted fluid administration beforehand and vigorous restoration
      of organ perfusion afterwards is now replacing the old resuscitation paradigm.
      Perhaps this shift in practice has helped this patient to survive.

PMID- 12009227
TI  - Cardiopulmonary arrest induced by anaphylactoid reaction with contrast media.
AB  - Anaphylactoid reactions to iodinated contrast media can cause life-threatening
      events and even death. A 44-year-old woman presented with cardiopulmonary arrest
      (CPA) immediately following the administration of nonionic iodinated contrast
      media for an intravenous pyelography. Her cardiac rhythm during CPA was asystole.
      She was successfully resuscitated by the radiologists supported by paged
      emergency physicians using the prompt intravenous administration of 1 mg of
      epinephrine. Neither laryngeal edema nor bronchial spasm was observed during the
      course of treatment, and she was discharged on the 4th day without any
      complications. The patient did not have a history of allergy, but had experienced
      a myocardial infarction and aortitis. She had undergone 11 angiographies and had
      been taking a beta-adrenergic receptor antagonist. Planned emergency medical
      backup is advisable to ensure resuscitation in the event of an anaphylactoid
      reaction to the use of contrast media in-hospital settings.

PMID- 12009228
TI  - Emergency needle cricothyroid puncture and thoracocentesis.

PMID- 12009229
TI  - The ILMA in pre-hospital care.

PMID- 12009230
TI  - Hypofractionated irradiation for non-small cell lung cancer.
AB  - Large radiation fractions are an effective way of killing tumour cells but have
      generally been avoided in curative treatment of patients because of concerns of a
      disproportionate increase in late normal tissue toxicity. Radiobiological
      modelling of the effect of radiation on lung tumours and late-reacting normal
      tissues, which are more sensitive to large radiation fractions, has been
      undertaken. The biological effect of radiation on tumours is increased as the
      overall treatment time is shortened but this is not true for late-reacting normal
      tissue. Sample data are shown in which the relative increases in radiation effect
      on the tumour and late-reacting normal tissues are similar after
      hypofractionation. A favourable therapeutic ratio can be achieved because the
      bulk of normal tissue will receive a lower dose of radiation at a lower dose per
      fraction than the tumour, especially with current techniques where the volume of
      normal tissue irradiated can be sharply reduced. The clinical evidence confirms
      that lung toxicity is volume-dependent. It is the small Stage I and II tumours
      which are most likely to benefit from hypofractionated regimens, as the volumes
      to be treated are smaller and they have a lower incidence of distant metastases.
      Patients with Stage III tumours with favourable prognostic factors are nowadays
      treated with combined chemotherapy and radiotherapy and so for this group more
      conservative hypofractionation regimens are being explored. However, more
      advanced tumours may be treated with hypofractionation to lower total doses to
      achieve palliation and a modest degree of survival benefit.

PMID- 12009231
TI  - Inhibition of proliferation of human small cell lung cancer cells expressing an
      autocrine system for gastrin releasing peptide by antisense oligodeoxynucleotides
      to gastrin releasing peptide receptor.
AB  - The objectives of this study were to investigate the effect of antisense (AS)
      oligodeoxynucleotides (ODNs) directed against gastrin releasing peptide (GRP)
      receptor mRNA on proliferation of human small cell lung cancer (SCLC) NCI-H345
      cells which express the autocrine system for GRP. The methods used were to expose
      human SCLC cell lines to antisense ODNs or sense ODNs and to measure their
      proliferation by spectrophotometric assay or viable cell counts. Our results
      demonstrated that the single or combined AS ODNs against GRP receptor inhibited
      proliferation of human SCLC NCI-H345 cells significantly by 37% (P<0.01), but did
      not inhibit proliferation of either human bronchial epithelial BEAS 2B cells or
      human SCLC NCI-N417 cells, neither of which express the GRP autocrine system. The
      sense controls did not significantly inhibit proliferation compared with no
      treatment controls. Specificity was also demonstrated by the observation that
      cells exposed to AS ODNs had a decrease in GRP receptor expression as measured by
      specific binding of 34% (P<0.01), and when all three AS ODNs were used, binding
      was decreased by 60% (P<0.03). Furthermore, AS ODNs decreased by 75% the maximum
      percentage of cells responding to GRP in an intracellular calcium release assay.
      Our conclusions are that antisense ODNs directed against a GRP receptor which is
      involved in an autocrine loop in human SCLC cells inhibited proliferation of
      these cells by their impact on reducing GRP receptor expression. Further
      development of means of increasing AS ODN specificity and effectiveness in human
      SCLC cell is warranted.

PMID- 12009232
TI  - Polymorphism of DNA ligase I and risk of lung cancer--a case-control analysis.
AB  - DNA ligases catalyze the joining of single and double-strand DNA breaks, which is
      an essential step in DNA replication, recombination and repair. Recently, a
      common single nucleotide polymorphism (A-->C) in exon 6 of DNA ligase I (LIG1)
      was identified, but its functional relevance remains to be determined. Because
      LIG1 participates in DNA repair and reduced DNA repair capacity is associated
      with risk of lung cancer, we evaluated in a non-population-based case-control
      study of 530 lung cancer cases and 570 cancer-free controls the role of this
      polymorphism in susceptibility to lung cancer. All of the subjects were non
      Hispanic whites and the controls were frequency-matched to cases on age, sex and
      smoking status. Using the polymerase chain reaction-restriction fragment length
      polymorphism method, we found that this LIGI A-->C substitution was very common
      in healthy controls and that the A and C allele frequencies were close to 0.5.
      However, there was no significant difference in the frequency distributions of
      LIGI genotypes between lung cancer cases and controls (25.7, 49.8 and 24.5% in
      cases and 26.1, 49.7 and 24.2% in controls for the AA, AC and CC genotypes,
      respectively). Therefore, there was no evidence to support an association between
      this polymorphism and the risk of lung cancer (adjusted odds ratio (OR)=1.06, 95%
      confidence interval (CI)=0.76-1.49 for AC versus CC and OR=0.93, 95% CI=0.64-1.36
      for AA versus CC) neither in all cases nor in different histopathologic types.
      The results of this large case-control study suggest that this LIG1 polymorphism
      may not play an important role in susceptibility to lung cancer.

PMID- 12009233
TI  - Expression of peroxisome proliferator activated receptor-gamma in non-small cell
      lung carcinoma: correlation with histological type and grade.
AB  - Peroxisome Proliferator Activated Receptor-gamma (PPAR-gamma) is a ligand
      activated transcription factor belonging to the steroid receptor superfamily. It
      is a key regulator of adipogenic differentiation and glucose homeostasis, the
      ligands of which have also been demonstrated to induce differentiation in human
      breast, lung and colon cancer cell lines. In the present study, PPAR-gamma
      expression in cases of non-small cell lung carcinoma (NSCLC) was examined
      immunohistochemically and was correlated with tumor histological type and grade.
      Primary tumor samples from 147 patients with NSCLC were immunostained using a
      monoclonal antibody against PPAR-gamma. Positive PPAR-gamma immunostaining was
      prominent in 61 out of 147 cases (42%) and negative in the rest. PPAR-gamma
      positivity was prominent in 37 out of 79 cases (47%) of squamous cell lung
      carcinoma and in 24 out of 68 ones (35%) of lung adenocarcinoma. PPAR-gamma
      positivity was most frequently observed in squamous cell tumors (P=0.021) and in
      tumors of high histological grade of both histological types (P=0.041). Well
      differentiated adenocarcinoma cases presented increased frequency for PPAR-gamma
      positivity compared with moderately and poorly differentiated ones (P=0.001). The
      intensity and pattern of PPAR-gamma staining in tumor cells were not correlated
      with histopathological parameters in PPAR-gamma positive cases of NSCLC examined.
      Our findings support evidence for participation of this protein in the biological
      mechanisms underlying the carcinogenic evolution in the lung, suggesting also the
      importance of specific PPAR-gamma ligands as future therapeutic approach in lung
      cancer.

PMID- 12009234
TI  - Predictive role of HER-2/neu overexpression and clinical features at initial
      presentation in patients with extensive stage small cell lung carcinoma.
AB  - Although recent advances in therapy have improved the quality of life in patients
      with extensive stage small cell lung cancer (ESSCLC), prolonged survival is still
      uncommon. To determine the role of HER-2/neu overexpression and other clinical
      predictors (symptoms at presentation) of adverse outcome in ESSCLC, we performed
      a retrospective study on subjects with a biopsy-proven diagnosis of ESSCLC. HER
      2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on
      paraffin-embedded specimens. An IHC score of > or = 2+ was considered positive
      for overexpression. Between 1991 and 2000, 223 patients with ESSCLC were
      identified, of whom 193 patients (84 females, 109 males) with a mean age of 68.5
      years (range: 42-90 years) had adequate tissue specimens for HER-2/neu testing.
      The symptoms at initial presentation and proportionate number of patients were:
      weight loss 61 (31.6%), cough 53 (27.5%), dyspnea 33 (17.1%), mass on chest
      radiograph 18 (9.3%), chest pain 15 (7.7%), asymptomatic 14 (7.2%) and others
      (weakness, lymphadenopathy, hoarseness and paraneoplastic syndromes) 29 (15.0%).
      Of the 193 specimens, 57 (29.5%) revealed HER-2/neu overexpression. The median
      survival for patients with ESSCLC who were HER-2/neu positive was 8 months
      (range: 1-25.5 months) while that in the HER-2/neu negative group was 16 months
      (range: 2-34 months). Interestingly, after adjusting for age, performance status
      and type of therapy, subset analysis revealed that the survival was significantly
      lower in HER-2/neu positive individuals (P<0.001; Mann-Whitney U-test). In our
      study, weight loss and cough were the two most common (59%) presenting complaints
      in patients with ESSCLC. Also, since HER-2/neu positivity was a marker for poor
      prognosis in ESSCLC, testing for overexpression may play a role in identifying
      patients at risk for shortened survival. Further studies would delineate whether
      HER-2/neu overexpression renders SCLC chemoresistant and thus, adversely affects
      outcome. There exists a need for randomized controlled trials to assess the role
      of Herceptin (alone or in combination with standard chemotherapy) in patients
      with ESSCLC.

PMID- 12009235
TI  - What is the role of HER-2/neu and trastuzumab (Herceptin) in lung cancer?

PMID- 12009236
TI  - Prognostic impact of Cyfra21-1 and other serum markers in completely resected non
      small cell lung cancer.
AB  - PURPOSE: The aim of this prospective study was to assess the prognostic impact of
      serum tumor markers (Cyfra21-1, carcinoembryonic antigen, neuron-specific
      enolase, squamous cell carcinoma-antigen and TPAcyk) in patients with non-small
      cell lung cancer (NSCLC) receiving complete resection. METHODS: Sixty-seven
      patients with histologically proven NSCLC and complete resection of stage I-IIIA
      disease were included. The serum levels of all markers were measured using
      commercially available immunoassays. RESULTS: With a median follow-up of 86
      months for surviving patients, those with initial Cyfra21-1 serum levels higher
      than 3.57 ng/ml had a significantly worse prognosis (P=0.014). The remaining
      serum tumor markers showed no prognostic impact. In a Cox regression model,
      Cyfra21-1 proved to be an independent prognostic factor for both overall survival
      and disease-free interval. In addition, Cyfra21-1 sustained as an independent
      prognostic factor in completely resected stage I/II disease. CONCLUSIONS: With a
      cut-off value of 3.57 ng/ml, Cyfra 21-1 was an independent prognostic factor for
      survival in NSCLC-patients with complete resection. Further evaluation is needed,
      particularly in stage I/II disease. When the prognostic impact is confirmed with
      larger patient numbers this may contribute to the identification of
      stratification variables for future treatment approaches of NSCLC.

PMID- 12009237
TI  - Intrabronchial orthotopic propagation of human lung adenocarcinoma-
      characterizations of tumorigenicity, invasion and metastasis.
AB  - Using the intrabronchial orthotopic propagation method, we evaluated the
      biological characteristics of human adenocarcinoma cell lines in vivo and
      examined the expressions of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and
      their related proteins. Nine human lung adenocarcinoma cell lines, including
      A549, NCI-H23, NCI-H322, NCI-H358, Calu-3, PC-14, LC-2/ad, RERF-LC-KJ and PL16T,
      were injected into the peripheral bronchi of mice using this method. The mice
      were sacrificed at 4 and 8 weeks after tumor cell propagation and the lungs and
      other organs were observed macroscopically and histologically. We classified the
      adenocarcinoma cell lines, according to their intrapulmonary tumorigenicity, into
      the following three groups: (A) those that showed a high incidence of
      intrapulmonary implantation (>50%) (A549 and NCI-H358). A549 showed mediastinal
      lymph node metastasis and pleural dissemination; (B) those that showed a low
      incidence of intrapulmonary implantation (PC-14, NCI-H322, NCI-H23, Calu-3, and
      LC-2/ad); (C) those that showed no tumorigenicity in the lung (RERF-LC-KJ and
      PL16T). In order to characterize the biological differences between each cell
      line, we investigated the expressions of MMP-2 and MMP-9 and their related
      molecules by northern blot analysis. The expressions of MMP-2 and MMP-9 and their
      activators (membrane-type 1-MMP and urokinase-type plasminogen activator) were
      thought to be associated with the growth, invasion and metastasis of the human
      lung adenocarcinoma cell lines examined.

PMID- 12009238
TI  - Characteristics of long-term survivors of untreated lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a malignant tumor with poor prognosis.
      Although the prognostic variables determining short-term survival have been well
      described, relatively little attention has been paid to factors associated with
      long-term survival. In search of these factors we studied the expression of
      several molecular markers in NSCLC. Only tumor samples of patients with squamous
      cell carcinomas and stage III tumors with a postoperative survival of at least 5
      years and those of patients who died within 2 years after resection were selected
      for this study. The expression of several parameters including oncogene and
      suppressor gene products, proliferative, apoptotic, angiogenic and resistance
      related factors were investigated and the differences in these two extreme
      populations were determined by the Wilcoxon rank sum test. Factors involved in
      proliferation (ras, fos, erbB-1, jun, cyclin A) were downregulated whereas
      factors involved in apoptosis (p53, bcl-2, CD95) were upregulated in the long
      survival group. Direct measurement of parameters of proliferation (cell cycle
      analysis by flow cytometry, PCNA index) revealed a lower proliferative activity
      in tumors of the long survivors compared to short survivors. In conclusion,
      tumors of the long survival group are characterized by a downregulation of
      factors involved in proliferation and an upregulation of factors involved in
      apoptosis. These tumors may grow more slowly and this may influence long-term
      survival of patients with NSCLC.

PMID- 12009239
TI  - Alveolar shrinkage in bronchioloalveolar carcinoma without central fibrosis.
AB  - Preservation of alveolar architecture in small bronchioloalveolar carcinoma (BAC)
      is one of the most important factors for predicting their prognosis, alveolar
      shrinkage in BAC, however, has not been studied well. In ten cases of pure BAC
      without collapse or central fibrosis, we measured two two-dimensional (2D)
      parameters; side-length of the alveoli facing alveolar ducts and circumference of
      the alveoli forming complete circles. And we also examined three-dimensionally
      (3D) elastic fibers and myofibroblasts in the thick sections. In BAC, 2D
      parameters showed alveolar shrinkage. The elastic fibers forming the alveolar
      framework, including the alveolar orifice, were 3D sinuous and bent in BAC, and
      suggested that alveolar shrinkage cased by folding of the alveolar wall.
      Myofibroblasts lay transversely and longitudinally in the interstitium in BAC,
      intertwined with the elastic fibers. Proliferation of myofibroblasts may be of
      importance in alveolar wall-folding and alveolar shrinkage in BAC.

PMID- 12009240
TI  - Prognostic significance of high-resolution CT findings in small peripheral
      adenocarcinoma of the lung: a retrospective study on 64 patients.
AB  - OBJECTIVE: We studied the prognostic importance of high-resolution CT (HRCT)
      findings in lung adenocarcinomas. PATIENTS AND METHODS: HRCT findings (lesion
      size, percentage of ground-glass opacity (GGO) areas of lesion, and presence or
      absence of lobulation, coarse spiculation, air space, pleural tag, and
      multiplicity of lesion), clinical data (age and surgical method), and pathologic
      findings (tumor subtypes and presence or absence of nodal metastasis) in 64
      consecutive patients with 64 peripheral adenocarcinomas of 20 mm or less (mean,
      13 mm), including 36 women and 28 men with a mean age of 64 years were analyzed
      and correlated with survival of the patients using Kaplan-Meier method and
      stepwise Cox proportional hazards modeling. Follow-up periods of the patients
      ranged from 6 to 45 months (mean, 22 months). Tumors were classified into six
      subtypes (types A-F) according to tumor growth patterns defined by Noguchi et al.
      RESULTS: Six (9%) of the 64 patients died of lung cancer. In univariate analyses,
      a significant difference was noted for lesion size (P=0.043), the percentage of
      GGO areas (P=0.005), and tumor subtypes (P=0.006). Lesion size of <15 mm (n=35),
      a lesion with GGO areas of >57% (n=36), and type A (n=16) or type B
      adenocarcinomas (n=16) indicated a significantly better survival. In multivariate
      analyses using these three parameters as independent variables, the percentage of
      GGO areas was the only significant independent factor for survival (P=0.044,
      relative risk=0.95). CONCLUSION: GGO areas measured on HRCT may have an
      independent prognostic significance of small adenocarcinomas of the lung.

PMID- 12009241
TI  - FDG-PET imaging and the diagnosis of non-small cell lung cancer in a region of
      high histoplasmosis prevalence.
AB  - STUDY OBJECTIVE: Determine the sensitivity and specificity of [F-18]-fluorine-2
      deoxy-D-glucose positron emission tomography (FDG-PET) in differentiating non
      small cell lung cancer (NSCLC) from benign solitary pulmonary nodules (SPNs) in a
      region with a high endemic rate of histoplamosis. DESIGN: Prospective, clinical
      study. SETTING: University, tertiary referral hospital in the upper Mississippi
      River valley. PATIENTS: Ninety patients with SPNs. INTERVENTIONS: Independent
      interpretation of FDG-PET imaging, computed tomography and pathologic evaluation
      of the SPNs. MEASUREMENTS AND RESULTS: To detect malignant SPNs, FDG-PET imaging
      had a sensitivity of 93%, a specificity of 40%, a positive predictive value (PPV)
      of 88% and a negative predictive value (NPV) of 55%. CONCLUSIONS: In a region
      with a high prevalence of pulmonary fungal infection, FDG-PET is sensitive but
      has a low specificity and NPV for identifying NSCLC. In our study cohort, FDG-PET
      does not appear to reduce the need for SPN biopsies.

PMID- 12009242
TI  - Docetaxel and carboplatin as second-line chemotherapy for metastatic non-small
      cell lung cancer.
AB  - The aim of this pilot study was to evaluate the activity and toxicity of
      docetaxel plus carboplatin as second-line treatment in patients with metastatic
      non-small cell lung cancer (NSCLC). Patients received docetaxel 75 mg/m(2)
      followed by carboplatin AUC 5 on day 1 every 3 weeks in an out-patient setting.
      Twenty-six patients were enrolled; 23 patients were diagnosed stage IV disease
      and three patients had a IIIB disease with malignant pleural effusion. The median
      interval from first to second-line treatment was 3.5 months (range 1-13).
      Patients received a total of 101 cycles with a median number of four cycles per
      patient (range 1-6). Five patients achieved a partial remission (19.23%; 95%
      confidence interval (CI) 6.55-39.35%), 11 had stable disease (42.31%) and ten
      progressed (38.46%) after initiation of second-line therapy. Median survival was
      243 days (95% CI 182-336 days), the median progression-free survival was 118 days
      (95% CI 89-170 days), and the 1-year survival rate was 25.98% (95% CI 6.33
      45.63%). Moderate haematological and mild nonhaematological toxicities were
      observed. No treatment-related death occurred. In conclusion, docetaxel plus
      carboplatin as second-line regimen has a reasonable activity with good tolerance
      and encouraging survival data.

PMID- 12009243
TI  - Second-line chemotherapy for non-small cell lung cancer: is more better or just
      simply more?

PMID- 12009244
TI  - A phase III randomized trial comparing vindesine and cisplatin with or without
      ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow
      up results and analysis of prognostic factors.
AB  - In order to evaluate the activity and toxicity of a three-drug combination of
      vindesine, ifosfamide and cisplatin (VIP) for inoperable non-small-cell lung
      cancer (NSCLC), we conducted a randomized trial comparing VIP with a two-drug
      combination of cisplatin and vindesine (VP). Between September 1987 and March
      1992, a total of 132 patients with stage III or IV NSCLC were randomly allocated
      to either VIP or VP. The VIP regimen consisted of vindesine (VDS 3 mg/m(2) on
      days 1 and 8), ifosfamide (IFX 1300 mg/m(2) on days 1-5), and cisplatin (CDDP 20
      mg/m(2) on days 1-5). The VP regimen consisted of VDS and CDDP with the same dose
      and schedule as the VIP regimen. Both regimens were repeated every 4 weeks.
      Objective response rates were 49.3% (95% confidence interval: 95%CI, 43.1-55.4%)
      in the VIP arm and 44.6% (95%CI, 38.4-50.2%) in the VP arm; the difference was
      not significant (P=0.5390). Median response duration, median survival time, and
      two-year survival rates were 26.5 weeks, 49.6 weeks, and 14.9% in the VIP arm and
      28.7 weeks, 37.1 weeks, and 12.3% in the VP arm, respectively. There were also no
      significant differences between these two treatment arms. In comparison with the
      VP regimen, however, a survival advantage of the VIP regimen could be confirmed
      when the data were evaluated with Cox's multivariate analysis (P=0.0131). In both
      arms, the principal toxicity was myelosuppression, which was significantly more
      frequent in the VIP arm, although generally well tolerated. CONCLUSION: This
      study suggested the survival advantage of the VIP regimen over the VP regimen for
      treatment of patients with advanced NSCLC.

PMID- 12009245
TI  - Intensive chemotherapy with whole blood stem-cell support and concurrent chest
      radiotherapy in small cell lung cancer: a phase I/II trial.
AB  - Intensive chemotherapy combined with chest radiation may ameliorate survival in
      small cell lung cancer (SCLC). In a prospective study, we treated 18 patients
      with limited SCLC with an intensive sequential single agent (ifosfamide,
      carboplatin, etoposide and paclitaxel, (ICE-T)) chemotherapy with the support of
      unprocessed stem-cell enriched whole blood and G-CSF and concomitant bi
      fractionated chest radiotherapy (60 Gy). The treatment was delivered in a short
      time of 10 weeks. The results were compared with an historical patient group
      treated with six cycles of standard chemotherapy of etoposide and cisplatin and
      concomitant chest radiotherapy. After a 3-year median follow up, the 2-year
      progression free (PFS) and overall survival (OS) are 54 and 63% in the ICE-T
      group, respectively. In the control group, median PFS and OS were 13 and 17
      months and the 2-year PFS and OS were 32% (P=0.20) and 47% (P=0.25),
      respectively. This short and intensive chemo-radiotherapy regimen is well
      tolerated and induces promising survival results. The use of stem cell enriched
      whole blood should be investigated in larger randomized studies.

PMID- 12009246
TI  - Carboplatin plus vinorelbine plus G-CSF in elderly patients with extensive-stage
      small-cell lung cancer: a poorly tolerated regimen. Results of a multicentre
      phase II study.
AB  - PURPOSE AND METHODS: A multicentre phase II trial (single-stage design) was
      undertaken to test the activity and toxicity of carboplatin (AUC 5 according to
      Calvert, day 1) plus vinorelbine (25 mg/m(2) days 1 and 8) with lenograstim
      support, every 3 weeks in the first line treatment of elderly patients, aged 65
      or more, affected by extensive small-cell lung cancer (SCLC). The primary end
      point of the trial was the objective response rate. Twenty-three responses among
      37 patients were considered necessary to proceed to a phase III trial. RESULTS:
      Twenty-eight patients were enrolled (median age 70 years). Treatment was
      remarkably toxic. Three patients died while on treatment. Eleven patients (39.3%,
      95% exact confidence interval (CI): 21.5-59.4) had an objective response, that
      was complete in 2 cases. Median time to progression was 5.1 months (95% CI: 3.3
      6.7). Median survival was 7.9 months (95% CI: 4.8-14.4). CONCLUSION: Carboplatin
      plus vinorelbine is poorly tolerated and not sufficiently active to warrant phase
      III comparison with standard chemotherapy regimens in elderly patients with
      extensive SCLC.

PMID- 12009247
TI  - Desmoplastic small round cell tumour of the pleura: a case report with unusual
      follow-up.
AB  - In 1994 a 19-year-old woman presented with a few weeks history of back ache.
      Routine chest X-ray and CT examination revealed a lesion originating from the
      parietal pleura and destroying the ribs. The tumour was resected during
      thoracotomy. The histological examination raised the possibility of atypical
      carcinoid tumour. One year later the tumour recurred. After its re-resection, the
      patient received radiotherapy. Three years after the initial presentation
      multiple pulmonary metastases developed. The patient was treated with
      chemotherapy, receiving vincristine, epi-adriamycin and cyclophosphamide in 8
      cycles, which resulted in complete remission. Between 1998 and 1999 progressions
      and partial remissions were observed, while the patient received further cycles
      of chemotherapy. Histological revision was performed in 1999 and a final
      diagnosis of desmoplastic small round cell tumour of the pleura was made.
      Immunohistochemically co-expression of cytokeratin, vimentin, desmin, and NSE was
      observed. The patient died in June 2000. The whole follow-up period was 76
      months. We thought this case to be worth for presentation because this unusual
      long survival, which was probably due to the aggressive complex anticancer
      treatment.

PMID- 12009248
TI  - Successful management of solitary malar metastasis from lung cancer.
AB  - A right malar mass developed in a 68-year-old man who had undergone right upper
      and middle bilobectomy for lung cancer 2 years previously. The mass was diagnosed
      to be a malar metastasis from lung cancer and was surgically resected because no
      other metastases were found. The patient is well without signs of recurrence 5
      years after resection of the malar mass. This is the first report of a malar
      metastasis from lung cancer and of successful resection for malar metastasis.

PMID- 12009249
TI  - Preferential amino acid sequences in alumina-catalyzed peptide bond formation.
AB  - The catalytic effect of activated alumina on amino acid condensation was
      investigated. The readiness of amino acids to form peptide sequences was
      estimated on the basis of the yield of dipeptides and was found to decrease in
      the order glycine (Gly), alanine (Ala), leucine (Leu), valine (Val), proline
      (Pro). For example, approximately 15% Gly was converted to the dipeptide
      (Gly(2)), 5% to cyclic anhydride (cyc(Gly(2))) and small amounts of tri- (Gly(3))
      and tetrapeptide (Gly(4)) were formed after 28 days. On the other hand, only
      trace amounts of Pro(2) were formed from proline under the same conditions.
      Preferential formation of certain sequences was observed in the mixed reaction
      systems containing two amino acids. For example, almost ten times more Gly-Val
      than Val-Gly was formed in the Gly+Val reaction system. The preferred sequences
      can be explained on the basis of an inductive effect that side groups have on the
      nucleophilicity and electrophilicity, respectively, of the amino and carboxyl
      groups. A comparison with published data of amino acid reactions in other
      reaction systems revealed that the main trends of preferential sequence formation
      were the same as those described for the salt-induced peptide formation (SIPF)
      reaction. The results of this work and other previously published papers show
      that alumina and related mineral surfaces might have played a crucial role in the
      prebiotic formation of the first peptides on the primitive earth.

PMID- 12009250
TI  - Kinetics of reaction of DNA-bound Fe(III)bleomycin with ascorbate: interplay of
      specific and non-specific binding.
AB  - The aerobic redox reaction of Fe(III)bleomycin (Blm) and ascorbate was examined
      in the absence of DNA and in the presence of 7.5 and 25 calf thymus DNA base
      pairs per-drug molecule, in order to investigate the effect of DNA binding on the
      properties of FeBlm activation and DNA strand cleavage. Under these successive
      conditions, the rate of initial reduction of Fe(III)Blm became progressively
      slower and biphasic. Using 7.5 base pairs per-molecule of FeBlm, 2-3 times as
      much drug reacted in the faster step as with the larger DNA to drug ratio. In
      each case, the more rapid process was identified with the reaction of high spin
      Fe(III)Blm-DNA. With the smaller ratio, dioxygen consumption, formation of HO(2)
      Fe(III)Blm-DNA, and production of DNA strand breaks as measured by the formation
      of base propenal were largely rate limited by the initial reaction of ascorbate
      with Fe(III)Blm-DNA. After a burst of reaction with the larger ratio of base
      pairs to Fe(III)Blm, a small fraction of the total Fe(III)Blm, representing high
      spin Fe(III)Blm, entered a steady state as HO(2)-Fe(III)Blm-DNA. Thereafter,
      reaction of dioxygen and base propenal formation occurred slowly with similar
      first-order rate kinetics. In order to explain these results, it is hypothesized
      that the metal domain-linker of Fe(III)Blm adopts two conformations with respect
      to DNA. One, at specific binding sites, is relatively unreactive with ascorbate.
      The other, present at non-specific sites as HPO(4)-Fe(III)Blm, is readily
      reactive with ascorbate to generate HO(2)-Fe(III)Blm-DNA. At the larger base pair
      to drug ratio, movement of Fe(III)Blm between specific and non-specific sites to
      generate HO(2)-Fe(III)Blm is a necessary part of the mechanism of strand
      scission.

PMID- 12009251
TI  - Investigation of the release of iron from ferritin by naturally occurring
      antioxidants.
AB  - Ferritin is the main intracellular iron storage protein. The release of iron from
      ferritin in the presence of a number of phenolic based compounds of nutritional
      significance was studied at physiological pH. The release of iron was measured by
      monitoring the formation of the iron(II)-ferrozine complex. The kinetics of this
      process were studied in Hepes buffer (pH 7.00), at 37 degrees C. The order of
      ability to remove iron from ferritin is epigallocatechin>gallic acid methyl ester
      approximately equal to sinapic acid>ferulic acid. The presence of the oxyradical
      scavenger urea resulted in a slight inhibition in the release of iron from
      ferritin by both gallic acid methyl ester and epigallocatechin. The ability of
      each reagent to release iron is interpreted on the basis of their ability to (a)
      reduce the bound iron and (b) complex the iron with the oxidised form of the
      phenol, thus mobilising it from the protein. These studies indicate that some
      phenolic based compounds that have been epidemiologically associated with a
      negative effect on iron absorption in man, can individually mobilise and release
      iron from ferritin under suitable conditions.

PMID- 12009252
TI  - Synthesis and characterization of cobalt and nickel chelates of 5
      dimethylaminomethyl-2-thiouracil and their evaluation as antimicrobial and
      anticancer agents.
AB  - A new antimetabolite of adenine, viz. 5-dimethylaminomethyl-2-thiouracil, was
      synthesized using the Mannich reaction. Owing to the biological importance of
      metalloelements in many biological processes, especially metabolic processes,
      cobalt(II) and nickel(II) complexes were also synthesized and examined for their
      antimicrobial and anticancer activities. These new compounds were characterized
      structurally by various techniques ranging from micro-elemental analyses to
      spectral analyses. Cobalt(II) complexes were found to be four coordinate, among
      which the bromo, iodo, and nitrato complexes were polymeric. The nickel(II)
      isothiocyanato complex exhibited four-coordinate geometry and the remaining
      nickel(II) complexes were six coordinate. Thermodynamic and kinetic parameters
      evaluated based on TG/DSC suggested that the initial stage of thermal
      decomposition follows a diffusion-controlled mechanism and the final stage a
      chemically controlled mechanism. Antibacterial, antifungal, and antitumor studies
      undertaken for the above compounds indicated structure-activity relationships.
      These metalloderivatives were more active than the parent compound. The order of
      activity was influenced by the chelate geometry and thermal stability. Activity
      increased with a decrease in coordination number and increase in thermal
      lability.

PMID- 12009253
TI  - Binding of vanadate to human albumin in infusion solutions, to proteins in human
      fresh frozen plasma, and to transferrin.
AB  - The binding of vanadate (V) to human serum albumin (HSA) in infusion solutions,
      to human fresh frozen plasma (FFP), and to human transferrin (TF) was
      investigated over a wide concentration range. Free V concentrations were obtained
      by ultrafiltration. Total and free V concentrations were determined using
      electrothermal atomic absorption spectrometry (ETAAS). Binding parameters were
      obtained by non-linear regression. V only bound appreciably to HSA at low
      concentrations (<1 microM). The binding capacity of HSA was about 1000-fold lower
      than that of FFP and TF per mole of protein. Binding to FFP and TF in the
      concentration range investigated could be described by a combination of saturable
      and additional non-saturable binding. The respective maximal binding capacities
      (B(max), microM), dissociation constants (k(D), microM), and proportionality
      constants (C) for the non-saturable, linear binding were B(max)=27, k(D)=2.5,
      C=0.19 for FFP and B(max)=47, k(D)=0.47, C=0.38 for TF. The results suggest that
      V is predominantly bound to transferrin in FFP. It is concluded that HSA in
      infusion solutions represents a reservoir of readily accessible V. Nevertheless,
      given the high binding capacity of transferrin in plasma, the amount of vanadate
      delivered via the brief administration of HSA solutions is unlikely to be of
      major importance.

PMID- 12009254
TI  - Mitochondrial permeability transition and cytochrome c release induced by
      selenite.
AB  - Cytochrome c release and mitochondrial permeability transition (MPT) play
      important roles in apoptosis. In this study, we found that selenium, an essential
      trace element, induced mitochondrial membrane potential (Delta psi(m)) loss,
      swelling, and cytochrome c release in isolated mitochondria. All of the above
      observations were blocked by cyclosporin A (CsA), which is a specific inhibitor
      to permeability transition pore (PTP), indicating selenite-induced mitochondrial
      changes were mediated through the opening of PTP. In physiological concentration,
      selenite could induce mitochondria at low-conductance PTP 'open' probability,
      which is correlated to regulate the physiological function, whereas in toxic
      concentration, induce mitochondria at high-conductance PTP 'open' probability and
      rapidly undergo a process of osmotic swelling following diffusion toward matrix
      as for inducer (Ca(2+)/P(i)). Selenite also induced other mitochondrial marker
      enzymes including monoamine oxidase (MAO) and mitochondria aspartate
      aminotransferase (mAST). Oligomycin inhibited the selenite-induced cytochrome c
      release and Delta psi(m) loss, showing that F(0)F(1)-ATPase was important in
      selenite or Ca(2+)/P(i)-induced MPT.

PMID- 12009255
TI  - Study of the biological effects and DNA damage exerted by a new dipalladium-Hmtpo
      complex on human cancer cells.
AB  - The new dipalladium complex [Pd(2)(mu-mtpo-N(3),N(4))(2)(phen)(2)](NO(3))(2)
      (where phen=1,10-phenantroline; Hmtpo=5,7-dihydro-7-oxo-5
      methyl[1,2,4]triazolopyrimidine), (Pd(2)-Hmtpo, or complex I), interacts
      effectively with DNA plasmid (pBS), as studied by circular dichroism spectroscopy
      (CD), causing large helix distortions, altering the direction of the main DNA
      helix axis and producing unwinding of the DNA double helix. DNA damage induced by
      complex I was highly significant at 2.81 microM (ovarian carcinoma TG cell line),
      as assessed by comet assay, a dose at which all treated nuclei showed more than
      30% DNA migration to the comet tail. DNA damage effect is a consequence of
      genotoxicity and not a false positive response caused by cytotoxicity. In vitro
      cytotoxic assay on the two human tumor cell lines TG and BT-20 (breast
      carcinoma), shows that doses of 0.47, 1.41 and 2.81 microM produce significant
      antiproliferative effects after 4 days of treatment compared with control.
      Complex I was highly cytotoxic at 2.81 microM causing an inhibition of viable
      cells of 65.5%. Cisplatin (cis-DDP) exhibits lower cytotoxic activity in TG cells
      than dipalladium complex (a cisplatin dose of 6.67 microM inhibits 30.3%) and
      does not cause migration of DNA to comet tail.

PMID- 12009256
TI  - Three kinetically different inorganic phosphate entities in bovine casein
      micelles revealed by isotopic exchange method and compartmental analysis.
AB  - Much controversy exists concerning the way calcium phosphate is linked to milk
      phosphoproteins including caseins. Homoionic exchange of inorganic phosphate
      between micellar calcium phosphates (MCP) of casein micelles and solute
      phosphates in cows' milk was investigated using H(32)PO(4)(2-) as radiotracer.
      Compartmental analysis and modelling revealed the presence of three MCP-related
      inorganic phosphate compartments each representing a separate phosphate entity.
      The relative phosphate quantities per compartment, i.e. the quantities of
      kinetically identical phosphate ions per MCP-ion cluster, and their mean
      residence times are 2:1:1 and 818, 0.24 and 23 h, respectively. Hence each MCP
      ion cluster comprises four inorganic phosphate ions divided over three intra-MCP
      binding sites each characterised by a mean residence time for homomolecular
      phosphate exchange at solution/MCP interface.

PMID- 12009257
TI  - Solvent effects on the stability of nifuroxazide complexes with cobalt(II),
      nickel(II) and copper(II) in alcohols.
AB  - A spectrophotometric study of the complexation of nifuroxazide with cobalt(II),
      nickel(II) and copper(II) was carried out in different alcohols. The formation of
      a complex in each case is reported and their stability constants have been
      calculated. For a given solvent, the stability of the complexes increases from
      cobalt to copper. In the case of copper(II), the stability varies as an inverse
      function of the dielectric constant of the solvent. A possible structure of the
      complex is proposed.

PMID- 12009258
TI  - Fractionation of vanadium in urine of Wistar rats as a function of time after
      intraperitoneal injection.
AB  - [(48)V]Vanadium was intraperitoneally injected into Wistar rats. Urine and feces
      were collected at regular intervals (n=19) between 1 and 144 h after injection.
      In case of urine, maximal excretion (V activity/ml urine) of vanadium was seen 3
      h after injection. In case of feces, a maximum appeared 32 h after injection.
      Urine samples were fractionated on two types of gel filtration column (Superose
      12 HR 10/30 and Superdex Peptide 10/30). We found that vanadium in urine exists
      as both high (protein-bound) and low molecular mass species and that the
      partition about these forms depends on the time elapsed after injection. After 1
      h, respectively, four (one high molecular and three low molecular mass species)
      and five (one high molecular and four low molecular mass species) vanadium peaks
      were present in the chromatograms of the Superose 12 and the Superdex Peptide
      columns. Then 3 h after injection, a different high molecular species showed up
      in the chromatograms, while the first high molecular and some low molecular mass
      species disappeared. Vanadium in urine after 8 h occurred as one high (slightly
      different from the high molecular complex after 3 h) and one low molecular mass
      complex. However, after 48 h the pattern changed again and vanadium in urine was
      excreted largely as one low molecular mass species, presumably one of the species
      that also occurred 1 h after injection but was not present in the period 6-24 h.

PMID- 12009259
TI  - Exploratory data analysis in functional neuroimaging.

PMID- 12009260
TI  - A novel, direct spatio-temporal approach for analyzing fMRI experiments.
AB  - We introduce a novel approach to couple temporal similarity with spatial
      neighborhood information. This is achieved by concatenating the K nearest,
      spatially contiguous neighbors of a pixel time-course (TC) of T time-instances.
      This produces a new TC of (K+1)T time instances. Depending on how "nearest" is
      defined, we have various options. Strictly spatial nearness means augmenting a
      given TC by its K nearest neighbors in some canonical spatial order. A more
      powerful and flexible option is to order the TCs to be concatenated according to
      their temporal similarity to the central voxel TC. For this study, we have chosen
      Pearson's cross-correlation coefficient as the measure of similarity. For more
      than a single neighbor, two concatenation options are possible. The direct
      ordering option requires that the TCs to be concatenated be spatially contiguous
      to the central pixel. The more flexible indirect option merely demands that one
      of a chain of temporally similar TCs be spatially connected to the central pixel.
      We also apply the temporal similarity criterion to the more conventional spatial
      (median) filtering, and show that it gives superior result to a strict spatial
      filtering. The method is tested and verified on a null fMRI dataset onto which we
      superposed two types of "activations" with known temporal behavior and spatial
      location. It is also applied to a real dataset containing visual activation. We
      also propose a strategy, based on the flexibility of the method, to determine a
      consensus, "core" set of activations.

PMID- 12009261
TI  - Node merging in Kohonen's self-organizing mapping of fMRI data.
AB  - In this paper, Kohonen's self-organizing mapping (SOM) is used as a data-driven
      technique for analyzing functional magnetic resonance imaging (fMRI) data. Upon
      the completion of an SOM analysis, a cluster merging technique, based on
      examining the reproducibility of the fMRI data across epochs, is utilized to
      merge SOM nodes whose feature vectors are sufficiently similar to one another.
      The resulting 'super nodes' give time course templates of potential interest.
      These templates can be subsequently used in traditional template-based analysis
      methods, such as cross-correlation analysis, yielding statistical maps and
      activation patterns. This technique has been demonstrated on two fMRI datasets
      obtained from a visually-guided motor paradigm and a visual paradigm,
      respectively, showing satisfactory results.

PMID- 12009262
TI  - Exploring fMRI data for periodic signal components.
AB  - We use a Bayesian framework to detect periodic components in fMRI data. The
      resulting detector is sensitive to periodic components with a flexible number of
      harmonics and with arbitrary amplitude and phases of the harmonics. It is
      possible to detect the correct number of harmonics in periodic signals even if
      the fundamental frequency is beyond the Nyquist frequency. We apply the signal
      detector to locate regions that are highly affected by periodic physiological
      artifacts, such as cardiac pulsation.

PMID- 12009263
TI  - Exploring regions of interest with cluster analysis (EROICA) using a spectral
      peak statistic for selecting and testing the significance of fMRI activation time
      series.
AB  - Much relevant information about activations and artifacts in a functional
      magnetic resonance imaging (fMRI) dataset can be obtained from an exploratory
      cluster analysis. In contrast to testing the significance of the measured
      experimental effect for a given model, unsupervised pattern recognition
      techniques, such as fuzzy clustering, often find unexpected behavior in addition
      to expected activations, allowing the exploitation of this element of surprise.
      The many artifact clusters often discovered might aid the experimenter in
      deciding whether the dataset is usable, whether some additional preprocessing
      step is required, or whether the one used has introduced spurious effects.
      However, clustering alone does not complete the analysis because the membership
      values that are generated are not indicative of the level of statistical
      significance with respect to the cluster activation patterns (centroids). This is
      of particular importance for fMRI datasets for which most time-series are
      "noise", with no activation patterns. We propose that an initial partition step
      should precede the clustering step. Only time-series that meet a certain
      statistical criterion (using a scaled version of Fisher's g-order statistic) are
      selected for clustering; this typically represents <5% of the whole brain region.
      The purpose of clustering is to generate a set of cluster centers that are the
      possible activation patterns; these are used in forming a linear model of all the
      time-series. The model parameter is tested for significance in both the time and
      frequency domains. We present a novel method of conducting these tests, which
      limits the number of false positives. We call the three-step process of initial
      partition, clustering and the two-domain significance test as exploring regions
      of interest with cluster analysis (EROICA).

PMID- 12009264
TI  - An evaluation of methods for detecting brain activations from functional
      neuroimages.
AB  - Brain activation studies based on PET or fMRI seek to explore neuroscience
      questions by statistically analyzing the acquired images to produce statistical
      parametric images (SPIs). An increasingly wide range of univariate and
      multivariate analysis techniques are used to generate SPIs in order to detect
      mean-signal activations and/or long-range spatial interactions. However, little
      is known about the comparative detection performance of even simple techniques in
      finite data sets. Our aims are (1) to empirically compare the detection
      performance of a range of techniques using simulations of a simple image phantom
      and receiver operating characteristics (ROC) analysis, and (2) to construct two
      near-optimal detectors, both generalized likelihood ratio tests as upper
      performance bounds. We found that for finite samples of (10-100) images, even
      when the t-test with single-voxel variance estimates (single-voxel t-test) is the
      "correct" (i.e. unbiased) model for simple local additive signals, better
      detection performance is obtained using pooled variance estimates or adaptive,
      multivariate covariance-based detectors. Normalization by voxel-based variance
      estimates causes significantly decreased detection performance using either
      single-voxel t-tests or correlation-coefficient thresholding compared to pooled
      variance t-tests or covariance thresholding, respectively. Moreover, we found
      that SVD by itself, or followed by an adaptive Fisher linear discriminant,
      provides a detector that is (1) more sensitive to mean differences than a single
      voxel t-test, (2) insensitive to the large local signal variances detected by
      covariance thresholding, and (3) much more sensitive to signal correlations than
      correlation-coefficient thresholding. Adaptive, multivariate covariance-based
      approaches and pooled-variance t-tests represent promising directions for
      obtaining optimal signal detection in functional neuroimaging studies.

PMID- 12009266
TI  - Flu in the limelight.

PMID- 12009267
TI  - 2nd meeting on novel adjuvants currently in/close to human clinical testing.
      World Health Organization-Organization Mondiale de la Sante Fondation Merieux,
      Annecy, France, 5-7 June 2000.

PMID- 12009268
TI  - Antibody responses to recombinant hepatitis B vaccines.

PMID- 12009269
TI  - Pneumococcal polysaccharide vaccine: a systematic review of clinical
      effectiveness in adults.
AB  - Pneumococcal polysaccharide vaccine is recommended in western countries for
      individuals at high risk of pneumococcal illness. We undertook a systematic
      review of randomised controlled trials of pneumococcal vaccine in adults, to
      determine the effects on clinical outcomes. RESULTS: In industrialised
      populations, no benefit was detected for outcomes other than pneumococcal
      bacteraemia, and this did not reach statistical significance. In non-industrial
      populations, clear benefit was demonstrated for mortality and all-cause
      pneumonia. CONCLUSION: Benefit from pneumococcal vaccination depends on the
      baseline risk of infection and characteristics of a given population. Evidence
      from randomised trials for widespread adult vaccination in industrial countries
      is lacking.

PMID- 12009270
TI  - Streptococcus pneumoniae polysaccharides conjugated to the outer membrane protein
      A from Klebsiella pneumoniae elicit protective antibodies.
AB  - Polysaccharides (PSs) derived from Streptococcus pneumoniae include more than 90
      serotypes and differ greatly in their immunogenicity. In addition, immunization
      with PSs does not induce high affinity antibody production and no memory B-cells
      are generated. Coupling PSs to carrier proteins has been reported to induce B
      cell maturation and to install a B-cell memory. As an alternative carrier
      protein, the outer membrane protein A (OmpA) derived from Klebsiella pneumoniae
      has been coupled to various PSs. We evaluated the immunogenicity of two PS
      conjugates, using PS derived from S. pneumoniae types 14 and 19. In this report,
      we show that anti-PS IgG responses are generated after the conjugation of PSs to
      P40. In addition, the humoral response generated is able to protect mice from a
      bacterial challenge. Our results indicate that P40 could be included in the
      development of new PS conjugate vaccines.

PMID- 12009271
TI  - Influence of dose and immunization route on the serum Ig G antibody response to
      BSA loaded PLGA microspheres.
AB  - BSA was entrapped into PLGA 50:50 microspheres and the in vitro release study was
      performed. Then 1 microg of microencapsulated antigen was subcutaneously
      administered to Balb/c mice and the serum Ig G response was compared to that
      obtained after the subcutaneous administration of the same amount of only free
      antigen or of free antigen emulsified 1:1 with Freund's complete adjuvant (FCA).
      The specific serum Ig G responses obtained from the microencapsulated antigen
      were higher than those obtained from the free antigen and similar to those
      obtained from the antigen emulsified with FCA. Therefore, the immune response
      obtained with the subcutaneous administration of 1 microg of microencapsulated
      antigen was used as a positive control to compare the immune response elicited by
      the administration of the spheres either by the oral or the intranasal route.
      There is a dose/response relationship in the serum Ig G response elicited after
      three consecutive oral administrations of microencapsulated antigen at a dosing
      range from 200 to 50 microg. However, this relationship does not seem to be clear
      for the intranasal administration of the spheres at the same dosing range. When
      comparing the serum Ig G responses at each dosing level for the different routes
      of administration, it can be observed that the intranasal route is a more
      powerful inducer of the production of specific Ig G antibody than the oral, which
      could be due to a greater permeability of the nasal epithelium and to qualitative
      differences between the mechanisms of induction of the immune response by each
      route. The serum Ig G2a versus Ig G1 ratio is not significantly different among
      all the groups that received antigen in microspheres.

PMID- 12009272
TI  - Hepatitis B surface antigen (HBsAg) derived from yeast cells (Hansenula
      polymorpha) used to establish an influence of antigenic subtype (adw2, adr, ayw3)
      in measuring the immune response after vaccination.
AB  - As a product of western world biotechnology the yeast (Saccharomyces cerevisiae)
      hepatitis B vaccine was introduced as antigenic subtype adw2. However, an
      HBsAg/adw2-vaccine may provide a good but not "optimal" immunologic response for
      infection with heterologous virus strains. The availability of the yeast
      Hansenula polymorpha HBsAg in three different antigenic forms (adw2, ayw3 and
      adr) enabled us to investigate the influence of variant amino acids in the
      binding of immune anti-HBs after vaccination. Hansenula-derived HBsAg was
      standardised on the basis of protein content at >95% purity. Standardisation was
      controlled by monoclonal anti-HBs binding in a well-conserved region. Sera were
      obtained after immunisation with type adw, ayw and adr vaccines. Direct binding
      of immune antibodies to homologous antigen (in EIA) was higher than to
      heterologous antigen except for the adr-related antibodies. Since the binding of
      the WHO reference anti-HBs was strongly reduced for the ayw and adr compared to
      the adw antigen, a similar binding profile for the three antigens on protein
      basis could result in 2-3-fold different anti-HBs level expressed in IU/l.
      Inhibition of Hansenula-derived HBsAg binding to solid phase monoclonal anti-HBs
      in enzyme immunoassays after incubation with serum anti-HBs confirmed the
      differential binding of serum anti-HBs with variant Hansenula-derived HBsAg. This
      variant (antigenic subtype) dependent reactivity of anti-HBs in immunoassays in
      combination with a variant specific WHO standard may limit the application of the
      threshold levels of 10 and 100 IU/l for seroconversion and seroprotection.

PMID- 12009273
TI  - Biological consequences of antigen and cytokine co-expression by recombinant
      Streptococcus gordonii vaccine vectors.
AB  - To test the effect of co-expression of immunomodulatory molecules, together with
      target antigen, two recombinant Streptococcus gordonii strains were constructed
      which secreted either murine interleukin-2 (IL-2) or interferon-gamma (IFN-gamma)
      in addition to a surface anchored test antigen (the conserved C-repeat region
      (CRR) of the M6 protein of Streptococcus pyogenes). The secretion of functional
      cytokines by S. gordonii was achieved by in-frame fusion of sequences encoding
      mature IL-2 or IFN-gamma to the sequences encoding the leader signal of the M6
      protein. Expression of the M protein CRR region from a separate chromosomal site
      produced double recombinants expressing a secreted cytokine and the M protein CRR
      region anchored to the surface. Protein expression was verified by streak blot,
      immunoblot, and ELISA on both the single and double recombinants. A cytokine
      bioassay using HT-2 cells verified biological activity of recombinant IL-2
      secreted from S. gordonii. When mice were immunized subcutaneously with the
      different S. gordonii expression strains, cytokine co-expression apparently
      modulated the systemic immune response. These results show that streptococci can
      deliver biologically active molecules such as cytokines along with antigens to
      the immune system. These results demonstrate that a cytokine-secreting,
      noninvasive, bacterial vaccine vector can be used to modulate immune responses to
      a co-expressed antigen.

PMID- 12009274
TI  - Determination of the virulence of the pigmentation-deficient and pigmentation
      /plasminogen activator-deficient strains of Yersinia pestis in non-human primate
      and mouse models of pneumonic plague.
AB  - The current human plague vaccine, a killed Yersinia pestis whole-cell
      preparation, does not protect against aerosol challenge and is reactogenic and
      antigenically undefined. Live attenuated Y. pestis, such as pigmentation
      deficient (Pgm-) strains, have been used frequently as vaccines and are
      efficacious. They are used widely in plague research and assumed to be safe.
      However, they can cause serious adverse reactions, and their aerosol infectivity
      is not known. We tested the virulence of a defined Pgm- variant of the C092
      strain of Y. pestis in mouse and non-human primate models of pneumonic plague.
      The ten-fold lower median lethal dose by the aerosol compared to the subcutaneous
      (s.c.) routes of the Pgm- strain in mice suggested that the Pgm- strain might be
      less attenuated by the former than by the latter route. After exposure of 16
      African green monkeys to inhaled doses ranging from 1.1 x 10(4) to 8.1 x
      10(7)cfu, eight died and eight survived. The terminal cultures collected from
      five of the non-survivors were all positive for Y. pestis. Two of the remaining
      three non-survivors were culture-negative but had pathologic and immunologic
      evidence of infection with Y. pestis, specimens could not be obtained nor the
      cause of death determined for the third one. The deaths were not dose-related,
      and there were some differences in the pathology associated with infection by the
      Pgm- strain compared to the wild-type (wt) strain. However, the Pgm- derivative
      was clearly virulent for monkeys by the aerosol route. A mutant of the Pgm-
      strain, which has a deletion in the plasminogen activator (Pla) virulence locus
      (pla), appeared to be more attenuated than was either the Pgm- single mutant (in
      NHPs and mice) or the Pla- single mutant strain (in mice) and has potential as a
      live vaccine.

PMID- 12009275
TI  - Subtype specificity of anti-HBs antibodies produced by human B-cell lines
      isolated from normal individuals vaccinated with recombinant hepatitis B vaccine.
AB  - Hepatitis B surface antigen (HBsAg) constitutes of an immunodominant determinant
      common to all subtypes of hepatitis B virus (HBV) and four major subtypic
      determinants. Subtype specificity of the human antibody response to HBsAg has
      already been partially studied in vivo at serum level. No comprehensive data,
      however, is available at the cellular level. In this study, the methods of
      Epstein-Barr virus (EBV) transformation and limiting dilution assay (LDA) were
      used to establish a large number of B-cell lines secreting anti-HBs antibody from
      34 adult individuals who were good-responders to the recombinant hepatitis B
      vaccine (HBsAg/adw). Specificity of 222 B-cell lines was assayed by sandwich
      ELISA and immunoblotting, of which 216 samples (97.3%) were identified to be anti
      a, 5 samples (2.3%) as anti-d and one sample (0.4%) as anti-w. The isotype of
      most of the anti-HBs antibodies was IgG and belonged to the IgG1 subclass. These
      findings which have not already been extensively investigated at the cellular
      level in human confirm and extend previous circumstantial results achieved in
      mouse and further prove the immunodominant role of the "a" determinant of HBsAg
      in antibody response in human.

PMID- 12009276
TI  - Rabies DNA vaccination of non-human primates: post-exposure studies using gene
      gun methodology that accelerates induction of neutralizing antibody and enhances
      neutralizing antibody titers.
AB  - Pre-exposure DNA vaccination protects non-human primates against rabies virus.
      Post-exposure protection of monkeys against rabies virus by DNA vaccination has
      not been attempted. Presumably, post-exposure experiments have not been
      undertaken because neutralizing antibody is usually slow to be induced after DNA
      vaccination. In this study, we initially attempted to accelerate the induction of
      neutralizing antibody by varying the route and site of DNA vaccination and
      booster frequency. Gene gun (GG) vaccinations above axillary and inguinal lymph
      nodes or in ear pinnae generated higher levels of neutralizing antibody than
      intradermal (ID) needle vaccinations in the pinnae. Concurrent GG booster
      vaccinations above axillary and inguinal lymph nodes and in ear pinnae, 3 days
      after primary vaccination, accelerated detectable neutralizing antibody. GG
      booster vaccinations also resulted in higher neutralizing antibody levels and
      increased the durability of this response. Post-exposure vaccination with DNA or
      the human diploid cell vaccine (HDCV), in combination with an one-time treatment
      with human rabies immune globulin (HRIG), protected 50 and 75% of the monkeys,
      respectively, as compared to 75% mortality of the controls. These data will be
      useful for the refinement, development, and implementation of future pre- and
      post-exposure rabies DNA vaccination studies.

PMID- 12009277
TI  - Immunogenicity of anti-Haemophilus influenzae type b CRM197 conjugate following
      mucosal vaccination with oligodeoxynucleotide containing immunostimulatory
      sequences as adjuvant.
AB  - Most vaccines are delivered by injection. Mucosal vaccination would increase
      compliance and decrease the risk of spread of infectious diseases due to a
      reduction of mucosal colonization and of contaminated syringes. However, most
      vaccines are unable to induce immune responses when administered mucosally, and
      require the use of strong adjuvant or effective delivery systems. Synthetic
      oligodeoxynucleotides (ODN) containing CpG immunostimulatory sequences (ISS) have
      been shown to act as potent adjuvants of type-1 immune responses also when
      mucosally co-administered with protein or peptide vaccines. We have shown that
      ISS can increase the anti-polysaccharide polyribosyl ribitol phosphate (PRP)
      antibody titres and anti-diphtheria toxin neutralizing antibody, if used as
      adjuvant of anti-Haemophilus influenzae type b (Hib) PRP vaccine conjugated with
      cross-reacting material (CRM) of diphtheria toxin in mice. Here, we show that ISS
      have the potential to increase host local and systemic antibody response against
      both the PRP and the protein component of a conjugated vaccine when mucosally
      administered in mice. Mucosal administration of Hib-CRM vaccine induced anti-PRP
      and neutralizing anti-diphtheria toxin antibodies of all the IgG subclasses, with
      a predominance of type-1 immune response-associated IgG2a and IgG3. At odds with
      systemic administration, the mucosal delivery of Hib-CRM induced anti-PRP and
      anti-diphtheria toxin mucosal IgA. These data envisage the feasibility of a
      mucosal vaccination with an already licensed Hib-CRM vaccine to achieve both an
      anti-H. influenzae and -diphtheria effective protection.

PMID- 12009278
TI  - Potency, sterility and immunogenicity of rabies tissue culture vaccine after
      reconstitution and refrigerated storage for 1 week.
AB  - The economical Thai Red Cross intradermal (TRC-ID) post-exposure rabies treatment
      schedule is now widely used in Asia. However, directives from WHO and
      manufacturers mandated that the vaccine be used within 8h after reconstitution of
      the freeze-dried product. This limits the use of TRC-ID to large animal bite
      clinics that see several rabies exposed patients daily. This study demonstrated
      that refrigerated purified chick embryo and Vero cell rabies vaccines can be
      stored safely for up to 7 days after reconstitution; allowing use of this
      treatment regimen in clinics that see few rabies exposed subjects. A large
      project applying this method in a Northern Thai canine rabies endemic province is
      now in place.

PMID- 12009279
TI  - Adult infection with hepatitis A despite declining endemicity; in favor of adult
      vaccination.
AB  - Seropositivity against hepatitis A was examined among 4806 standing army
      personnel (4497 males and 309 females) during 1998-1999. Each bi-annual birth
      cohort examined showed a decline in seropositivity compared to the previous one.
      When compared with a study performed in 1989, however, for each of the 1961-1962,
      1963-1964, 1965-1966, 1967-1968 and 1969-1970 birth cohorts examined, the 1998
      1999 study showed 5-15% higher seropositivity. This trend remained after
      controlling for differences between the two studies in ethnic origin, sibship
      size and level of education. The overall seroconversion rate is estimated as
      1.15% per year and the clinical to subclinical ratio as 1:14. Thus, hepatitis A
      infection continues to occur in the young adult age group and vaccination of this
      group should be considered.

PMID- 12009280
TI  - Evaluation of 12 stabilizers in a developed attenuated Salmonella Enteritidis
      vaccine.
AB  - The development of a stable live attenuated Salmonella Enteritidis (SE) vaccine,
      resisting heat stress during transportation and storage in unequipped tropical
      and subtropical zones of the world, is highly recommended. Twelve stabilizers
      were individually supplemented into a 9 ml volume of sterile distilled water
      resulting in concentrations of 1, 2, 3, 4 and 5%. A volume of 1 ml of attenuated
      live SE vaccine is added over the 9 ml of each concentration of the stabilizers.
      The differently stabilized SE vaccines were stressed at 55 degrees C for 48 h.
      The lowest percent reductions in SE cell viability by specified level of each
      stabilizer in ascending order were: 22.3% by 2% skim milk, 55.1% by 5% bovine
      serum albumin (BSA), 59.2% by 4% sorbitol, 74.4% by 3% maltose, 75% by 2% honey,
      91.3% by 3% histidine, 96.9% by 1% heparin, 97.5% by 4% dextrose, 97.9% by 5%
      lactose, 99.4% by 5% sucrose, 99.5% by 2% gelatin, and 100% by 1-5% glycerol. In
      narrowing the concentration levels of skim milk to include 1.00, 1.25, 1.50,
      1.75, 2.00, 2.25, 2.50, 2.75, and 3.00%, the 2.50% was the optimum level
      resulting in minimal percent reduction in SE cell viability of 18.9% after
      exposure to the defined heat stress.

PMID- 12009281
TI  - Induction of local innate immune responses and modulation of antigen uptake as
      mechanisms underlying the mucosal adjuvant properties of immune stimulating
      complexes (ISCOMS).
AB  - Lipophilic immune stimulating complexes (ISCOMS) containing the Quil A adjuvant
      can induce local and systemic immune responses against orally delivered protein
      antigens. Here, we have examined the possibility that ISCOMS act by modulating
      local innate immune responses and antigen uptake in the intestine. Feeding ISCOMS
      to mice induced recruitment of dendritic cells (DCs), activated macrophages
      (mphi) and lymphocytes into the mesenteric lymph node (MLN), as well as
      recruitment of macrophages and B cells into the PP. Feeding ISCOMS also enhanced
      the absorption into circulation of a test feed of ovalbumin (OVA), with
      accelerated kinetics and increased peak levels. Serum taken 1h after feeding a
      tolerogenic dose of OVA to mice given ISCOMS orally did not induce the tolerance
      of systemic delayed type hypersensitivity (DTH) and antibody responses found in
      mice receiving serum from donors fed OVA alone. Thus, ISCOMS may increase the
      immunogenicity of intestinal antigen via a combination of effects on antigen
      uptake and on local accessory cells.

PMID- 12009282
TI  - Safety, tolerability and immunogenicity of new formulations of the Plasmodium
      falciparum malaria peptide vaccine SPf66 combined with the immunological adjuvant
      QS-21.
AB  - SPf66 is a synthetic malaria peptide vaccine, which has been widely tested in
      combination with aluminium hydroxide (alum) as the adjuvant. Since this
      formulation is weakly immunogenic, we sought to improve its immunogenicity by
      using the saponin adjuvant QS-21. SPf66/QS-21 vaccines were evaluated for safety,
      tolerability and immunogenicity in healthy adults. The vaccines were found to be
      safe in 87/89 (97.8%) volunteers studied. However, two individuals developed
      severe vaccine allergy following the third dose of 1/3 SPf66/QS-21 formulations
      tested. Vaccine formulations containing QS-21 induced a 45- to over 200-fold
      increase in anti-SPf66 IgG titres over the alum formulation after the second and
      third doses, respectively. Anti-SPf66 antibody from some subjects reacted against
      asexual blood stage parasites, as demonstrated by immunofluorescence and
      immunoblotting. Antibody responses generated by the QS-21 formulations were of
      longer duration compared to those evoked by the alum formulation. While
      SPf66/alum has been found to induce only CD4+ T cell response, the QS-21
      formulations exhibited the potential to also elicit SPf66-specific CD8+
      responses. These observations demonstrate that the use of QS-21 can substantially
      enhance the immunogenicity of peptide vaccines, such as SPf66.

PMID- 12009283
TI  - Immunisation of dairy cattle with recombinant Streptococcus uberis GapC or a
      chimeric CAMP antigen confers protection against heterologous bacterial
      challenge.
AB  - The gapC genes, encoding the cell surface-associated GapC proteins of S. uberis
      and S. agalactiae, have been cloned and sequenced. To identify potential vaccine
      candidates against S. uberis-induced bovine mastitis, lactating dairy cows were
      vaccinated with either (6 x His)GapC of S. uberis or S. dysgalactiae, or with a
      chimeric CAMP-factor antigen, CAMP-3. For 7 days following heterologous challenge
      with S. uberis, milk somatic cell counts were determined to assess differences in
      the severity of mastitis between vaccinates and an unvaccinated control group.
      Vaccination with S. uberis (6 x His)GapC or CAMP-3 resulted in a significant
      reduction in inflammation on several days post-challenge, most significantly for
      the former antigen. Inflammation was not reduced in S. dysgalactiae (6 x His)GapC
      vaccinates, suggesting that it does not confer cross-species protection.

PMID- 12009284
TI  - Virosome-mediated delivery of protein antigens to dendritic cells.
AB  - Virosomes are reconstituted viral membranes in which protein can be encapsulated.
      Fusion-active virosomes, fusion-inactive virosomes and liposomes were used to
      study the conditions needed for delivery of encapsulated protein antigen
      ovalbumin (OVA) to dendritic cells (DCs) for MHC class I and II presentation.
      Fusion-active virosomes, but not fusion-inactive virosomes, were able to deliver
      OVA to DCs for MHC class I presentation at picomolar OVA concentrations. Fusion
      activity of virosomes was not required for MHC class II presentation of antigen.
      Therefore, virosomes are an efficient system for delivery of protein antigens for
      stimulation of both helper and CTL responses.

PMID- 12009285
TI  - Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by
      interleukin-12 in Rhesus macaques.
AB  - The adjuvant effect of recombinant Rhesus macaque interleukin-12 (RhIL-12) on the
      induction of cellular and humoral immune responses elicited by the HIV-1 subunit
      vaccine protein gp120 in Rhesus macaques was examined. RhIL-12 in conjunction
      with gp120 was given at day 0, 28 and 84 intramuscularly. Coadministration
      resulted in an approximate 10-fold increase in plasma anti-gp120 antibody levels
      as compared to levels generated in control monkeys receiving gp120 alone.
      Potentiation of the humoral arm of the immune response was evident by both ELISA
      and an antiviral bioassay. In addition, RhIL-12 was found to produce a
      significant increase in gp120-specific proliferative responses and in the
      frequency of antigen-specific IFN-gamma and IL-2 producing T cells after
      restimulation of PBMC with gp120 in vitro indicating that RhIL-12 potentiates
      cell-mediated immune responses as well. A critical finding was that during the
      course of the study, RhIL-12 did not induce a neutralizing antibody response to
      the administered cytokine. The doses of RhIL-12 were well tolerated and no
      detectable adverse side-effects on hematopoietic and hepatic parameters were
      noted. The data revealed that IL-12, when coadministered intramuscularly, acts as
      a potent adjuvant which is able to enhance not only cellular but also humoral
      immune responses to gp120 in non-human primates and may have to be considered in
      future HIV vaccine strategies.

PMID- 12009286
TI  - Micellar-type complexes of tailor-made synthetic block copolymers containing the
      HIV-1 tat DNA for vaccine application.
AB  - A novel class of cationic block copolymers constituted by a neutral hydrophilic
      poly(ethylene glycol) (PEG) block and a positively charged
      poly(dimethylamino)ethyl methacrylate block was prepared for delivery of DNA.
      These block copolymers spontaneously assemble with DNA to give in aqueous medium
      micellar-like structures. Five of these novel block copolymers (K1-5), differing
      in the length of both the PEG chain and the linear charge density of the
      poly(dimethylamino)ethyl methacrylate block, were prepared and analyzed for gene
      delivery, gene expression and safety. All five block copolymers protected DNA
      from DNAse I digestion and delivered the DNA into the cell. However, only three
      of them (K1, K2 and K5) released the DNA at level allowing efficient gene
      expression into cells. No toxic effects of both the copolymers alone or their DNA
      complexes were observed in vitro or in mice. In addition, copolymers were
      scarcely immunogenic. These results indicate that this novel class of cationic
      block copolymers is safe and possesses the biological characteristics required
      for DNA delivery, thus, representing promising vehicles for DNA vaccination.

PMID- 12009287
TI  - Experimental Chlamydia pneumoniae infection in NIH/S mice: effect of
      reinoculation with chlamydial or cell preparation on culture, PCR and
      histological findings of lung tissue.
AB  - The cellular components present in chlamydial preparations may contribute to the
      course of the experimental infection. NIH/S mice were inoculated and reinoculated
      intranasally with Chlamydia pneumoniae or a cellular preparation. The mock
      inoculation induced only mild histological changes in the lungs, which possibly
      induced partial protection against subsequent C. pneumoniae infection and, when
      given as reinoculation, possibly reactivated the culture-negative infection as
      culture-positive. In addition, serum antibodies against mouse heat shock protein
      60 (Hsp60) were found in a few mice. In conclusion, the main immunopathogenic
      factors in a C. pneumoniae mouse model are chlamydial components. However, a
      cellular preparation may participate in an inflammatory reaction. Autoimmunity
      against Hsp60 may also play a role in the pathogenesis of C. pneumoniae
      infection.

PMID- 12009288
TI  - Use of a rationally attenuated Bordetella bronchiseptica as a live mucosal
      vaccine and vector for heterologous antigens.
AB  - Inactivation of the aroA gene of Bordetella bronchiseptica severely impaired its
      ability to colonise the respiratory tract of mice. The B. bronchiseptica aroA
      mutant was investigated as a live vaccine and vector for heterologous antigens.
      The B. bronchiseptica aroA mutant expressing the non-toxic fragment C (FrgC) of
      tetanus toxin (strain GVB120) was used to immunise mice intranasally. Immunised
      mice produced a strong serum and mucosal antibody response to B. bronchiseptica
      and serum anti-FrgC antibodies. Upon challenge with wild type B. bronchiseptica,
      immunised mice rapidly reduced the numbers of B. bronchiseptica in their
      respiratory tract, although clearance was more pronounced in the lower than in
      the upper respiratory tract. Immunisation with GVB120 protected approximately 40%
      of mice from tetanus toxin challenge. As far as we are aware, this is the first
      description of a recombinant B. bronchiseptica strain being used as a live
      vaccine vector for heterologous antigens.

PMID- 12009289
TI  - Immune responses in mice to intranasal and intracutaneous administration of a DNA
      vaccine encoding Helicobacter pylori-catalase.
AB  - We previously reported that the intracutaneous injection of DNA vaccines encoding
      Helicobacter pylori heat shock proteins elicited specific immune responses, and
      led to reduced infection in mice. In this study, we constructed DNA vaccine
      encoding H. pylori-catalase (pcDNA3.1-kat) and investigated the immune responses
      to intranasal and intracutaneous administration of pcDNA3.1-kat. C57/BL6 mice
      were immunized intracutaneously with 10 microg of pcDNA3.1-kat or intranasally
      with 50 microg of pcDNA3.1-kat. Catalase-specific IgG antibody was detected in
      the sera of intranasal and intracutaneous immunized mice. Both intranasal and
      intracutaneous immunized mice were significantly protected from colonization by
      H. pylori and had significantly reduced degrees of gastritis. These results
      demonstrate that DNA vaccine encoding H. pylori-catalase can induce an immune
      response against H. pylori, and that intranasal immunization works as well as
      intracutaneous immunization.

PMID- 12009290
TI  - Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty
      virus-like particles on HIV-1 disease progression.
AB  - Long-term effects of therapeutic vaccination of human immunodeficiency virus
      (HIV)-1-infected subjects with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) on
      progression to AIDS, death, a CD4 cell count <or=200 cells/mm(3) and CD4 cell
      count decline were studied in a multicenter cohort study of 56 individuals who
      participated in a phase II double-blind placebo-controlled trial with p24-VLP in
      1993. Using Cox proportional hazard analysis, no difference between vaccine and
      placebo groups was found in progression to death (adjusted hazard rate (HR): 0.68
      (95% CI: 0.05-7.83), AIDS (adjusted HR: 1.07 (95% CI: 0.21-5.36)) and a CD4 cell
      count <or=200 cells/mm(3) (adjusted HR: 1.00 (95% CI: 0.35-2.87)). Using linear
      regression with correction for multiple visits within one person, no effect of
      vaccination on CD4 cell count decline, adjusted for antiretroviral therapy (ART)
      use, was found (P=0.98). In conclusion, therapeutic vaccination with p24-VLP is
      not related to slower HIV-1 disease progression.

PMID- 12009291
TI  - DNA immunization against the clumping factor A (ClfA) of Staphylococcus aureus.
AB  - Adhesins are considered the most important virulence factors during early phases
      Staphylococcus aureus infection. Antibodies induced by vaccination toward an
      adhesin should reduce the adherence of the pathogen and augment its phagocytosis.
      The present report describes the immune response of mice to a DNA vaccine
      directed against one of these adhesins, clumping factor A (ClfA). Injection of
      plasmids expressing the fibrinogen-binding region A of ClfA induced a strong and
      specific antibody response to ClfA in mice. In addition, splenocyte proliferation
      was provoked by in vitro stimulation with recombinant ClfA, thus, indicating
      direct implication of these cells in the immune response. Pre-incubation of S.
      aureus with sera of vaccinated mice reduced the pathogen's ability to bind
      fibrinogen by up to 92%. These pre-incubated bacteria were phagocytosed by
      macrophages at an increased level in vitro and were less virulent in vivo in a
      mouse mastitis model. However, DNA-immunized mice were not protected against an
      intraperitoneal challenge. Overall, the results suggest that DNA immunization
      against adhesins represents a new and valuable approach to combat S. aureus
      infections.

PMID- 12009292
TI  - Flt3 ligand and conjugation to IL-1beta peptide as adjuvants for a type 1, T-cell
      response to an HIV p17 gag vaccine.
AB  - The adjuvant activity of Flt3 ligand (Flt3L) and conjugation to an interleukin
      (IL)-1beta bioactive fragment were compared, either alone or in combination, for
      their ability to induce T- and B-cell responses to the HGP-30 peptide sequence
      (amino acids 86-115 of human immunodeficiency virus (HIV) gag p17). The
      efficiency of HGP-30/IL-1beta conjugation, Flt3L administration or both as
      adjuvants was examined and all were found to augment similar levels of delayed
      type hypersensitivity (DTH) responses. In contrast, significant antigen (Ag)
      specific types 1 and 2 T-cell ELISPOT responses were induced only by the
      combination of adjuvants. Further, in vitro sensitization with HGP-30 selectively
      increased Ag-specific, type 1 T-cell and cytotoxic T lymphocyte (CTL) responses
      to HGP-30-derived nonapeptide epitopes, while type 2 responses declined as
      measured in the ELISPOT assay. No serum antibodies to HGP-30 were induced unless
      HGP-30 was conjugated to keyhole-limpet hemocyanin. This suggests that a
      combination adjuvant strategy using Flt3L and conjugation to a biologically
      active IL-1beta fragment may be used to preferentially increase type 1 T-cell and
      CTL responses to HIV-1 gag antigenic epitopes.

PMID- 12009293
TI  - Monitoring anthrax vaccine safety in US military service members on active duty:
      surveillance of 1998 hospitalizations in temporal association with anthrax
      immunization.
AB  - We compared 1998 hospitalizations in active-duty US military personnel for
      possible temporal association with anthrax immunization. Immunization,
      demographic, and hospitalization data were analyzed using Cox proportional
      hazards modeling for hospitalization within 42 days of vaccination. Discharge
      diagnoses were aggregated into 14 International Classification of Disease, Ninth
      Revision, Clinical Modification (ICD-9-CM) categories. Approximately 11% of
      subjects received one or more doses of vaccine during 1998; those immunized were
      more likely to be younger and male. Lower hospitalization rates were observed
      across doses and diagnostic categories among the immunized. Adjusted risk ratios
      for hospitalization by diagnostic category suggest that immunized service members
      were at equal or lesser risk for hospitalization than the non-immunized.

PMID- 12009294
TI  - A new intra-NALT route elicits mucosal and systemic immunity against Moraxella
      catarrhalis in a mouse challenge model.
AB  - Mucosally administered antigens are often poorly immunogenic due to the
      difficulty of transporting antigens through the mucosal epithelium. We
      investigated a new route of intranasal-associated lymphoid tissue (intra-NALT)
      administration of antigens to circumvent the antigen transportation barrier. A
      comparative study was carried out on mice administered with killed whole cells of
      Moraxella catarrhalis strain 25238 plus cholera toxin (CT) by intra-NALT
      injection and nasal inoculation. Both routes induced significant elevations of
      several isotype antibodies against strain 25238 in saliva, lung lavage, and serum
      as measured by an enzyme-linked immunosorbent assay (ELISA). Most of these
      antibodies were paralleled by the numbers of their corresponding antibody forming
      cells in mucosal or systemic lymphoid tissues. However, intra-NALT injection
      elicited higher levels of immunoglobulin (Ig) A and IgG in saliva, IgA and IgG in
      lung lavage, and IgG and IgM in sera than nasal inoculation (P<or=0.05). In
      addition, both routes generated significant reductions of bacteria in lungs
      following an aerosol challenge with strain 25238 in a mouse model of pulmonary
      clearance. Once again, intra-NALT route showed better bacterial clearance in
      mouse lungs than nasal inoculation (P<0.01). These results demonstrate that intra
      NALT administration of antigens is a convenient and effective route for mucosal
      immunization that elicits improved mucosal and systemic immunity. This new route
      can be used as a model to study mucosal antigens or vaccine candidates for
      antigen activation and interaction with the NALT that is one of major inductive
      sites for common mucosal immune system.

PMID- 12009295
TI  - Evaluation of SIV library vaccines with genetic cytokines in a macaque challenge.
AB  - Gene and expression library immunization make it possible to functionally test
      all the gene-encoded antigens of a pathogen in a host challenge system. This
      comprehensive method could generate new and better vaccine candidates. We
      constructed expression libraries from simian immunodeficiency virus (SIV) cDNA
      and genetically immunize monkeys with the libraries alone or with a low dose of
      plasmids encoding human IL-12 and GMCSF. Eight of twelve animals in the three
      test groups showed some anti-SIV immune response, whereas the controls did not.
      Six months after priming, monkeys were intravenously challenged with virulent
      SIVmac251. All were infected but animals in two groups vaccinated with SIV
      libraries showed a trend toward lower viral-loads, mitigated clinical disease,
      and higher survival rates than controls. Significantly, co-administering the
      GMCSF and IL-12-encoding plasmids worsened these measures of protection. This
      preliminary study should encourage further development of library-vaccine
      strategies and caution the use of cytokines as adjuvants.

PMID- 12009296
TI  - Increased immunogenicity of HIV envelope subunit complexed with alpha2
      macroglobulin when combined with monophosphoryl lipid A and GM-CSF.
AB  - Critical to the success of HIV-1 subunit vaccines is the development of
      strategies to augment vaccine immunogenicity. Successful adjuvants must not only
      improve immunogenicity above current adjuvant levels, but must also decrease the
      dose of immunogen required for optimal immunogenicity. We have evaluated
      activated alpha2-macroglobulin (alpha2M*) and a squalene-based stable emulsion
      containing monophosphoryl lipid A (MPL-SE) with granulocyte-macrophage colony
      stimulating factor (GM-CSF) as adjuvants to enhance the immunogencity of
      candidate HIV immunogens. Balb/c mice were subcutaneously immunized on days 0, 14
      and 28 with 100-0.1 microg of HIV-1 envelope gp120 C4-V3 immunogens from either
      HIV IIIB (C4-V3(IIIB)) or SHIV 89.6P (C4-V3(89.6P)). Immunogens were tested
      covalently coupled to alpha2M*, formulated with MPL-SE/GM-CSF, or as a
      combination of both. Using CFA/IFA, only 50 and 100 microg, but not lower doses
      of C4-V3(IIIB) peptides, induced antibody responses. In contrast, peak antibody
      responses were detected in mice immunized with 10 microg of C4-V3 peptide coupled
      to alpha2M* (alpha2M*-peptide). Similar to CFA/IFA, MPL-SE/GM-CSF induced optimal
      antibody responses at 50 and 100 microg of C4-V3 immunogen. However, the
      combination of MPL-SE/GM-CSF with alpha2M*-C4-V3 peptide decreased the dose of C4
      V3 required for optimal response to 5 microg for C4-V3(IIIB), and to 0.1 microg
      for C4-V3(89.6P). Taken together, HIV envelope gp120 C4-V3 peptides covalently
      complexed with alpha2M* and formulated with MPL-SE/GM-CSF resulted in a subunit
      HIV immunogen capable of inducing anti-HIV envelope antibody responses at doses
      up to 100-fold less than those needed with CFA/IFA or MPL-SE/GM-CSF alone.

PMID- 12009297
TI  - Placental and breast transfer of antibodies after maternal immunization with
      polysaccharide meningococcal vaccine: a randomized, controlled evaluation.
AB  - We evaluated the strategy of maternal immunization with Neisseria meningitidis
      (Nm) vaccine in Asian mothers, to assess potential protection of infants,
      including by breast milk. One hundred and fifty-seven women in the third
      trimester were randomized to receive a single dose of the polysaccharide Nm
      (n=75) or a control vaccine (n=82). Group A Nm IgG levels were measured in
      maternal and infant sera, and specific IgA in breast milk. A 5.6-fold rise of Nm
      IgG antibody was observed among the Nm vaccinees. At delivery, geometric mean
      titres (GMTs) of Nm IgG antibody in Nm mothers was 12.5 microg/ml versus 4.97
      microg/ml, with a mean infant/maternal antibody ratio of 0.56. Infants of Nm
      vaccinees had mean IgG levels of 6.9, 2.3, 1.2 and 0.6 microg/ml at 0, 6, 14 and
      22 weeks, significantly higher than in control children up to 14 weeks. Anti-Nm
      IgA levels in milk were 6.8 to 2.0 microg/ml, significantly higher in Nm
      vaccinees till 6 months. Immunization during pregnancy is safe for both mothers
      and infants, and provides infants with significantly increased levels of specific
      IgG for 2-3 months and oral IgA for 6 months.

PMID- 12009298
TI  - RTS1-an eukaryotic terminator of replication.
AB  - Eukaryotic replication termination generally occurs randomly in the region
      between two active origins. However, termination, or pausing of the replication
      forks has been observed at specific loci. Recently, a site-specific terminator of
      replication named RTS1 was shown to play an important role in mating-type
      switching in Schizosaccharomyces pombe. Mating-type switching in S. pombe relies
      on an imprinting event that chemically modifies one strand of the DNA at the
      mating-type locus mat1. This imprint, that is formed only when mat1 is replicated
      in a specific direction, marks the DNA for a rearrangement leading to mating-type
      switching. The RTS1 element ensures that mat1 is replicated in the correct
      direction for imprinting and initiation of the subsequent mating-type switching
      event. This is the first replication terminator shown to play a role in cellular
      differentiation.

PMID- 12009299
TI  - NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression,
      purification, and kinetic properties.
AB  - GMP reductase (EC 1.6.6.8) is the only known metabolic step by which guanine
      nucleotides can be converted to the pivotal precursor of both adenine and guanine
      nucleotides. Human GMP reductase has been previously partially purified from
      erythrocytes and a chromosome 6-linked cDNA has been identified to correspond for
      encoding human GMP reductase. Here, we reported a distinct cDNA for human GMP
      reductase isoenzyme isolated from a human fetal brain library, and the GenBank
      accession number is AF419346. The deduced protein shows 90% identity with human
      GMP reductase reported (named GMPR1 compared with GMPR2 of this paper) and 69%
      with E. coli GMP reductase. Comparison of GMPR2 cDNA sequence with human genome
      indicates the corresponding gene spans about 6.6kb on chromosome 14, which
      encodes 348 amino acid residues. Northern hybridization analysis indicates a
      differential and disproportionate expression of mRNAs for GMPR1 and GMPR2,
      suggesting the existence of distinct molecular species of GMP reductase in human.
      The apparent Km of GMPR2 for NADPH and GMP are 26.6 and 17.4 microM,
      respectively. This is the first report suggesting the existence of two distinct
      types of human GMP reductase molecular species, which can be used to explain the
      bimodal saturation curve noted with the purified human erythrocyte GMP reductase.

PMID- 12009300
TI  - Peroxisome proliferator-activated receptor beta expression in human breast
      epithelial cell lines of tumorigenic and non-tumorigenic origin.
AB  - Peroxisome proliferator-activated receptor beta (PPARbeta) is a member of the
      nuclear hormone receptor superfamily and is a ligand activated transcription
      factor, although the precise genes that it regulates and its physiological and
      pathophysiological role remain unclear. In view of the association of PPARbeta
      with colon cancer and increased mRNA levels of PPARbeta in colon tumours we
      sought in this study to examine the expression of PPARbeta in human breast
      epithelial cells of tumorigenic (MCF-7 and MDA-MB-231) and non-tumorigenic origin
      (MCF-10A). Using quantitative RT-PCR we measured PPARbeta mRNA levels in MCF-7,
      MDA-MB-231 and MCF-10A cells at various stages in culture. After serum
      deprivation, MDA-MB-231 and MCF-10A cells had a 4.2- and 3.8-fold statistically
      greater expression of PPARbeta compared with MCF-7 cells. The tumorigenic cell
      lines also exhibited a significantly greater level of PPARbeta mRNA after serum
      deprivation compared with subconfluence whereas such an effect was not observed
      in non-tumorigenic MCF-10A cells. The expression of PPARbeta was inducible upon
      exposure to the PPARbeta ligand bezafibrate. Our results suggest that unlike
      colon cancer, PPARbeta overexpression is not an inherent property of breast
      cancer cell lines. However, the dynamic changes in PPARbeta mRNA expression and
      the ability of PPARbeta in the MCF-7 cells to respond to ligand indicates that
      PPARbeta may play a role in mammary gland carcinogenesis through activation of
      downstream genes via endogenous fatty acid ligands or exogenous agonists.

PMID- 12009301
TI  - Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light
      chain Tctex1 and the heat-shock protein PBP74.
AB  - The voltage-dependent anion-selective channel 1 (VDAC1), i.e. eukaryotic porin,
      functions as a channel in membranous structures as described for the outer
      mitochondrial membrane, the cell membrane, endosomes, caveolae, the
      sarcoplasmatic reticulum, synaptosomes, and post-synaptic density fraction. The
      identification of VDAC1 interacting proteins may be a promising approach for
      better understanding the biological context and function of the channel protein.
      In this study human VDAC1 was used as a bait protein in a two-hybrid screening,
      which is based on the Sos recruitment system (SRS). hVDAC1 interacts with the
      dynein light chain Tctex-1 and the heat-shock protein peptide-binding protein 74
      (PBP74)/mitochondrial heat-shock protein 70 (mtHSP70)/glucose-regulated protein
      75 (GRP75)/mortalin in vivo. Both interactions were confirmed by overlay-assays
      using recombinant partner proteins and purified hVDAC1. Indirect
      immunofluorescence on HeLa cells indicates a co-localisation of hVDAC1 with the
      dynein light chain and the PBP74. In addition, HeLa cells were transfected
      transiently with enhanced green fluorescent protein (EGFP)-hVDAC1 fusion
      proteins, which also clearly co-localise with both proteins. The functional
      relevance of the identified protein interactions was analysed in planar lipid
      bilayer (PLB) experiments. In these experiments both recombinant binding partners
      altered the electrophysiological properties of hVDAC1. While rTctex-1 increases
      the voltage-dependence of hVDAC1 slightly, the rPBP74 drastically minimises the
      voltage-dependence, indicating a modulation of channel properties in each case.
      Since the identified proteins are known to be involved in the transport or
      processing of proteins, the results of this study represent additional evidence
      of membrane-associated trafficking of the voltage-dependent anion-selective
      channel 1.

PMID- 12009302
TI  - Inhibition of acetylcholinesterase from Electrophorus electricus (L.) by
      tricyclic antidepressants.
AB  - The effects of tricyclic antidepressants drugs (TCA) amitriptyline, imipramine
      and nortriptyline, on purified Electrophorus electricus (L.) acetylcholinesterase
      (AChE; acetylcholine hydrolase, EC 3.1.1.7) were studied using kinetic methods
      and specific fluorescent probe propidium. The antidepressants inhibited AChE
      activity by a non-competitive mechanism. Inhibition constants range from 200 to
      400 microM. Dimethylated amitriptyline and imipramine were more potent inhibitors
      than the monomethylated nortriptyline. Fluorescence measurements using bis
      quaternary ligand propidium were used to monitor ligand-binding properties of
      these cationic antidepressants to the AChE peripheral anionic site (PAS). This
      ligand exhibited an eight-fold fluorescence enhancement upon binding to the
      peripheral anionic site of AChE from E. electricus (L.) with K(D)=7 x 10(-7)M. It
      was observed that TCA drugs displaced propidium from the enzyme. On the basis of
      the displacement experiments antidepressant dissociation constants were
      determined. Similar values for the inhibition constants suggest that these drugs
      have similar affinity to the peripheral anionic site. The results also indicate
      that the catalytic active center of AChE does not participate in the interaction
      of enzyme with tricyclic antidepressants. These studies suggest that the binding
      site for tricyclic antidepressants is located at the peripheral anionic site of
      E. electricus (L.) acetylcholinesterase.

PMID- 12009303
TI  - Enhanced utilization and altered metabolism of arginine in inflammatory
      macrophages caused by raised nitric oxide synthesis.
AB  - Nitric oxide (NO) production was increased in macrophages during inflammation.
      Casein-elicitation of rodents causing a peritoneal inflammation offered a good
      model to study alterations in the metabolism of L-arginine, the precursor of NO
      synthesis. The utilization of L-arginine for NO production, arginase pathway and
      protein synthesis were studied by radioactive labeling and chromatographic
      separation. The expression of NO synthase and arginase was studied by Western
      blotting.Rat macrophages utilized more arginine than mouse macrophages (228+/-27
      versus 71+/-12.8pmol per 10(6) macrophages). Arginine incorporation into proteins
      was low in both species (<15% of labeling). When NO synthesis was blocked,
      arginine was utilized at a lower general rate, but L-ornithine formation did not
      increase. The expression of enzymes utilizing arginine increased. NO production
      was raised mainly in rats (1162+/-84pmol citrulline per 10(6) cells) while in
      mice both arginase and NO synthase were active in elicited macrophages (677+/
      85pmol ornithine and 456+/-48pmol citrulline per 10(6) cells). We concluded, that
      inflammation induced enhanced L-arginine utilization in rodent macrophages. The
      expressions and the activities of arginase and NO synthase as well as NO
      formation were increased in elicited macrophages. Specific blocking of NO
      synthesis did not result in the enhanced effectivity of the arginase pathway,
      rather was manifested in a general lower rate of arginine utilization. Different
      rodent species reacted differently to inflammation: in rats, high NO increase was
      found exclusively, while in mice the activation of the arginase pathway was also
      important.

PMID- 12009304
TI  - Construction of an alkaline phosphatase-liposome system: a tool for
      biomineralization study.
AB  - Alkaline phosphatase is required for the mineralization of bone and cartilage.
      This enzyme is localized in the matrix vesicle, which plays a role key in
      calcifying cartilage. In this paper, we standardize a method for construction an
      alkaline phosphatase liposome system to mimic matrix vesicles and examine a some
      kinetic behavior of the incorporated enzyme. Polidocanol-solubilized alkaline
      phosphatase, free of detergent, was incorporated into liposomes constituted from
      dimyristoylphosphatidylcholine (DMPC), dilaurilphosphatidylcholine (DLPC) or
      dipalmitoylphosphatidylcholine (DPPC). This process was time-dependent and >95%
      of the enzyme was incorporated into the liposome after 4h of incubation at 25
      degrees C. Although, incorporation was more rapid when vesicles constituted from
      DPPC were used, the incorporation was more efficient using vesicles constituted
      from DMPC. The 395nm diameter of the alkaline phosphatase-liposome system was
      relatively homogeneous and more stable when stored at 4 degrees C. Alkaline
      phosphatase was completely released from liposome system only using purified
      phosphatidylinositol-specific phospholipase C (PIPLC). These experiments confirm
      that the interaction between alkaline phosphatase and lipid bilayer of liposome
      is via GPI anchor of the enzyme, alone. An important point shown is that an
      enzyme bound to liposome does not lose the ability to hydrolyze ATP,
      pyrophosphate and p-nitrophenyl phosphate (PNPP), but a liposome environment
      affects its kinetic properties, specifically for pyrophosphate. The
      standardization of such system allows the study of the effect of phospholipids
      and the enzyme in in vitro and in vivo mineralization, since it reproduces many
      essential features of the matrix vesicle.

PMID- 12009305
TI  - Anticancer effect of retinoic acid via AP-1 activity repression is mediated by
      retinoic acid receptor alpha and beta in gastric cancer cells.
AB  - To uncover the mechanisms relating to the anticancer effect of retinoic acids in
      gastric cancer cells, the mediation of activator protein-1 (AP-1) activity
      repression by retinoic acid receptors (RARs) was investigated. All-trans retinoic
      acid (ATRA) inhibited AP-1 activity in BGC-823 cells (RARalpha(+), RARbeta(+)),
      but not in MKN-45 cells (RARalpha(lo), RARbeta(-)). Transient transfection of
      RARbeta expression vector into MKN-45 cells significantly resulted in direct
      repression of AP-1 activity in a receptor concentration-dependent manner, and
      this could be strengthened by ATRA. Stable transfection of RARbeta into MKN-45
      cells directly inhibited cell growth and colony formation, and ATRA also enhanced
      these effects. Transient transfection of RARalpha into MKN-45 cells however,
      displayed receptor concentration-dependent AP-1 activity inhibition only in the
      presence of ATRA. Stable transfection of RARalpha into MKN-45 cells resulted in
      ATRA-dependent inhibition of cell growth and colony formation. For AP-1 binding
      activity induced by TPA, the repressive effect of ATRA was only observed in BGC
      823 and RARalpha and RARbeta stably transfected MKN-45 cells, but not in intact
      MKN-45 cells. This indicates the necessity for sufficient cellular RARalpha
      and/or RARbeta in order for AP-1 activity repression to occur. Deletion of DNA
      binding domain (DBD) of RARbeta, but not ligand binding domain (LBD), eliminated
      the anti-AP-1 function of RARbeta. It is therefore concluded that both RARalpha
      and RARbeta are mediators in the anticancer function of ATRA via AP-1 activity
      inhibition, and that RARbeta, not RARalpha, can inhibit AP-1 activity to a
      certain extent directly by itself. Thus DBD, not LBD, is critical for anti-AP-1
      activity.

PMID- 12009306
TI  - Thermodynamic analysis of human serum albumin interactions with glucose: insights
      into the diabetic range of glucose concentration.
AB  - The interaction of proteins with glucose results in their non-enzymatic glycation
      and influences their structural and functional properties. Human serum albumin
      (HSA) interacts with glucose forming glycated HSA. However, the glucose binding
      sites and the thermodynamic characteristics of the glycated HSA require further
      delineation. Here, the binding properties of HSA and glucose were studied
      utilizing fluorescent techniques. HSA was incubated with glucose in the 0-300mM
      range at 27 or 37 degrees C. The interaction of HSA with glucose showed two sets
      of binding sites. The first set consists of two sites with positive cooperativity
      and the second set consists of nine identical non-cooperative sites. The
      percentage of glycated HSA (gly%) and the moles of glucose bound to moles of HSA
      (r) were utilized to obtain binding constants and thermodynamic parameters based
      on the Wyman binding potential. The enthalpy of binding, obtained by van't Hoff
      relation, presented exothermicity up to 7mM glucose (126mg/dl, normal range) and
      endothermic propensity at higher glucose concentrations (>7mM, diabetic range).
      The start of endothermic propensity was consistent with the diabetic range of
      glucose concentration and indicates unfolding of HSA. The Gibbs free energy and
      entropy of binding further supports the unfolding of HSA. Therefore, glucose
      interacts with multiple sites on HSA affecting its biochemical and biophysical
      properties. This may interfere with HSA normal function contributing to diabetic
      complications.

PMID- 12009307
TI  - Effects of ATP on the stability of enzymes against heat treatment in 6
      aminonicotinamide treated quail.
AB  - The stabilities of liver and pectoral muscle enzymes in 6-aminonicotinamide (6
      AN) treated quail against heat treatment in the presence and absence of added ATP
      were investigated. Only ATP level in the brain and pectoral muscle of 6-AN
      treated group was significantly reduced compared to the control group whereas ADP
      and AMP levels were not affected. In the thermal stability (55 degrees C) of
      liver enzymes, the activity of acetylcholinesterase (AChE) was not affected
      whereas the activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and
      lactate dehydrogenase (LDH) were significantly lowered (P<0.01). The addition of
      1mM ATP to liver enzyme extracts of 6-AN group afforded 4- and 1.7-fold more
      protection for GAPDH and LDH, respectively (P<0.01). In liver, LDH appeared to be
      more protected by ATP than GAPDH. In muscle, however, GAPDH and AChE activity
      were significantly affected but not LDH. The addition of 1mM ATP to muscle enzyme
      extracts of 6-AN group afforded 1.7-fold more protection for GAPDH (P<0.01) but
      rather inactivated AChE. A marked reduction in ATP levels in muscle did not
      affect specifically muscle enzyme activities only since liver enzyme activities
      were also affected to the same degree as muscle.

PMID- 12009308
TI  - Stimulation of tetrahydrobiopterin synthesis by cyclosporin A in mouse brain
      microvascular endothelial cells.
AB  - We examined the effect of the immunosuppressant, cyclosporin A (CsA) on the
      synthesis of tetrahydrobiopterin (BH4), a cofactor for nitric oxide (NO) synthase
      and a scavenger of reactive oxygen species (ROS), in mouse brain microvascular
      endothelial cells. Treatment with CsA increased the BH4 content and the
      expression of mRNA level of GTP cyclohydrolase I, the rate-limiting enzyme of BH4
      synthesis. 2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTP cyclohydrolase I,
      strongly reduced the CsA-induced increase in BH4 content. Cycloheximide (CHX), a
      protein synthesis inhibitor, also reduced CsA-induced BH4 synthesis. These
      findings suggest that CsA stimulates BH4 synthesis via a de novo pathway with the
      induction of GTP cyclohydrolase I. Moreover, CsA-induced the mRNA level of the
      inducible type of NO synthase, and stimulated the L-citrulline formation from L
      arginine, which is a marker for NO synthesis. The CsA-stimulated L-citrulline
      formation was attenuated by the co-treatment with GTP cyclohydrolase I inhibitor.
      The expression of the endothelial type of NO synthase was low under basal
      condition, and was not affected by the treatment with CsA. These findings suggest
      that increase in BH4 content induced by CsA is coupled with NO production by
      inducible type of NO synthase.

PMID- 12009309
TI  - Novel protein kinase C isoforms and mitogen-activated kinase kinase mediate
      phorbol ester-induced osteopontin expression.
AB  - BACKGROUND AND AIMS: The expression of osteopontin (OPN), a protein postulated to
      play a role in tumorigenesis, is induced by the tumor promoter, 12-O
      tetradecanoylphorbol-13-acetate (TPA) in vivo and in the in vitro initiation
      promotion skin carcinogenesis model (JB6 cells). Although TPA-induced OPN
      expression in JB6 cells has been suggested to involve protein kinase C (PKC), the
      PKC isoforms and the downstream pathway mediating OPN expression have not been
      extensively studied. METHODS: Using the JB6 cell model, we determined the
      involvement of PKC isoforms, mitogen-activated protein kinase kinase (MAPK
      kinase/MEK) and MAPK in TPA-induced OPN expression using inhibitors specific to
      PKC isoforms and MEK and performing Northern blot analyses. Western blot analyses
      of cells treated with specific inhibitors were also performed to determine
      whether PKC isoforms or MEK were involved in activation of MAPK. KEY RESULTS: TPA
      increased the steady-state level of OPN mRNA as early as 2-4h and this expression
      persisted for at least 4 days. TPA induction of OPN expression in JB6 cells is
      mediated through PKC epsilon and PKC delta, which also mediated the
      phosphorylation of MAPK. Additionally, inhibition of MEK activity, which
      activates MAPK, attenuated TPA-induced OPN expression. These findings suggest
      that activation of MAPK is important in mediating OPN expression. CONCLUSION: TPA
      induced steady-state OPN mRNA expression in mouse JB6 cells involves the
      activation of MAPK mediated through PKC epsilon and/or PKC delta.

PMID- 12009310
TI  - Up-regulated expression of a novel gene in activated human peripheral blood
      mononuclear cells that is a truncated paralog of the human system L-amino acid
      transporter 1.
AB  - INTRODUCTION AND AIMS: The human system L-amino acid transporter1 (hLAT1) is one
      of the CD98 light chains and its gene has been mapped to chromosome 16q24. Our
      preliminary findings have indicated that in HeLa S3 cells there are transcripts
      whose nucleotide sequences are very similar but not identical to that of the
      amino acid transporter. This study intends to examine whether these novel
      transcripts have biological significance through elucidating their genetic
      aspects and expression profiles in human cells. METHODS: The expression levels of
      the transcripts were quantified by real-time PCR analysis. Chromosomal mapping of
      the gene was performed by fluorescence in situ hybridization (FISH). RESULTS:
      Three types of transcripts were identified and their nucleotide sequences were
      aligned with the chromosome 16p12 clone with high identity. They encoded 180- or
      190-amino acid proteins, showing 92-94% of amino acid identity to the amino
      terminal region of the hLAT1 (507 amino acids). However, their 3' non-coding
      sequences did not show homology to the nucleotide sequence of the amino acid
      transporter. Their genes were mapped to chromosome 16p11.2-p13.1 as low-copy
      repeats (LCRs). The transcription of one of these genes in peripheral blood
      mononuclear cells was significantly up-regulated when the cells were stimulated
      with concanavalin A. CONCLUSION: We have characterized the three truncated
      paralogs of the hLAT1 gene. It is suggested that the expression of one of these
      paralogs may play an important role in the activation of peripheral blood
      mononuclear cells.

PMID- 12009311
TI  - Ostrich antithrombin III: kinetics and mechanism of inhibition of ostrich
      thrombin.
AB  - A kinetic investigation of ostrich thrombin specificity, its regulation and
      evolutionary development in comparison to those of other well-characterised
      species may contribute to the understanding of the structure-function
      relationships of thrombin. Antithrombin III (ATIII) was purified from ostrich
      plasma by heparin-Sepharose and Super Q-650S chromatography. It exhibited a M(r)
      of 59.2K and a pI in the range of 5.2-6.0. The ostrich N-terminal sequence was
      compared to those of other known species and showed the highest identity with
      rabbit ATIII (31%). Inhibition studies included the interaction of ostrich and
      human ATIII with bovine, human and ostrich thrombin. At a 2:1 molar ratio of
      ostrich ATIII to enzyme, 20 and 40% remaining activity was found for bovine and
      ostrich thrombin, respectively. Ostrich thrombin exhibited a pH and temperature
      optimum of 9.0 and 60 degrees C, respectively. Hydrolysis of seven peptide p
      nitroanilide substrates by ostrich thrombin revealed D-Phe-Pip-Arg-pNA
      (k(cat)/K(m)=9.65 microM(-1)s(-1)) as the substrate with the highest catalytic
      efficiency. The effect of monovalent cations on ostrich thrombin catalysis
      revealed enhanced activity with Na(+). The calculated K(i) values for the complex
      formation between ostrich thrombin and ostrich (9.29 x 10(-11)M) and human (9.66
      x 10(-11)M) ATIII are comparable to reported results. The results obtained from
      the present study confirmed that ostrich thrombin and ATIII are closely related
      to the corresponding molecules of other species in terms of physicochemical and
      kinetic properties.

PMID- 12009312
TI  - Purification and properties of a lectin from ascomycete mushroom, Ciborinia
      camelliae.
AB  - A lectin was isolated from an ascomycete mushroom, Ciborinia camelliae which was
      specific to N-acetyl-D-galactosamine. On SDS-polyacrylamide gel electrophoresis;
      this lectin gave a single band of approximately 17-kDa in the presence of 2
      mercaptoethanol, but formed dimers, trimers and tetramers in its absence. Amino
      acid analysis revealed the lectin contained two cysteines and no methionine. The
      N-terminal sequence was determined up to residue 21, and no homologous proteins
      including other ascomycete lectins were found.

PMID- 12009313
TI  - Gene expression of 5-epi-aristolochene synthase and formation of capsidiol in
      roots of Nicotiana attenuata and N. sylvestris.
AB  - Three new copies of a sesquiterpenoid synthase gene encoding 5-epi-aristolochene
      synthase (EAS) were cloned as cDNAs from Nicotiana attenuata and functionally
      characterized after expression of the recombinant enzymes in E. coli.
      Differential patterns of EAS gene expression and formation of the antimicrobial
      sesquiterpenoid capsidiol were found in roots and shoots of two species of
      Nicotiana. EAS is expressed constitutively in roots of N. attenuata and N.
      sylvestris corresponding with constitutive capsidiol formation in roots.
      Constitutive expression of EAS and capsidiol accumulation were not detectable in
      shoots of rosette plants of N. attenuata, but accumulation of terpene synthase
      transcripts could be induced in shoots by feeding of the tobacco hornworm,
      Manduca sexta. Constitutive expression of EAS has not been previously reported
      from N. tabacum, where capsidiol is known as an elicitor- and pathogen-inducible
      phytoalexin. It is conceivable that capsidiol contributes not only to an
      inducible defense against pathogens, but also to a constitutive defense in an
      organ-specific manner in some species of Nicotiana.

PMID- 12009314
TI  - Cytokinins and gibberellins in sap exudate of the oil palm.
AB  - Exudates were collected from stumps of pre-anthesis inflorescences of oil palm
      and analysed for cytokinin and gibberellin content using combined HPLC-ELISA
      techniques. Three antisera, for zeatin-type, dihydrozeatin-type and
      isopentenyladenine-type cytokinins, were used in ELISAs to identify members of
      these three groups of cytokinins. Ribotides, 9-glucosides, free bases and
      ribosides were detected for each of the groups with zeatin riboside the most
      abundant cytokinin identified in the exudate. Isopentenyladenine-type and
      dihydrozeatin-type cytokinins were also identified but at lower levels. In
      addition, two monoclonal antibodies were used in the development of novel ELISAs
      for members of the 13-hydroxylated and non-13-hydroxylated families of
      gibberellins. The new ELISAs allow the determination of gibberellins in smaller
      amounts of tissue than are required for GC-MS. The most abundant gibberellins
      identified in exudates were GA19 and GA44, as well as other members of the early
      13-hydroxylation pathway. Gibberellins were confirmed by GC-MS. The presence of
      these types of growth regulators in exudate supplying immature inflorescences
      suggest they have a role in growth and development of these structures.

PMID- 12009315
TI  - Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea,
      kucha (Camellia assamica var. kucha).
AB  - Theacrine (1,3,7,9-tetramethyluric acid) and caffeine were the major purine
      alkaloids in the leaves of an unusual Chinese tea known as kucha (Camellia
      assamica var. kucha). Endogenous levels of theacrine and caffeine in expanding
      buds and young leaves were ca. 2.8 and 0.6-2.7% of the dry wt, respectively, but
      the concentrations were lower in the mature leaves. Radioactivity from S-adenosyl
      L-[methyl-14C]methionine was incorporated into theacrine as well as theobromine
      and caffeine by leaf disks of kucha, indicating that S-adenosyl-L-methionine acts
      as the methyl donor not only for caffeine biosynthesis but also for theacrine
      production. [8-14C]Caffeine was converted to theacrine by kucha leaves with
      highest incorporation occurring in expanding buds. When [8-14C]adenosine, the
      most effective purine precursor for caffeine biosynthesis in tea (Camellia
      sinensis), was incubated with young kucha leaves for 24 h, up to 1% of total
      radioactivity was recovered in theacrine. However, pulse-chase experiments with
      [8-14C]adenosine demonstrated much more extensive incorporation of label into
      caffeine than theacrine, possibly because of dilution of [14C]caffeine produced
      by the large endogenous caffeine pool. These results indicate that in kucha
      leaves theacrine is synthesized from caffeine in what is probably a three-step
      pathway with 1,3,7-methyluric acid acting an intermediate. This is a first
      demonstration that theacrine is synthesized from adenosine via caffeine.

PMID- 12009316
TI  - Accumulation of arachidonic acid-rich triacylglycerols in the microalga
      Parietochloris incisa (Trebuxiophyceae, Chlorophyta).
AB  - The freshwater green microalga Parietochloris incisa is the richest known plant
      source of the polyunsaturated fatty acid (PUFA), arachidonic acid (20:4omega6,
      AA). While many microalgae accumulate triacylglycerols (TAG) in the stationary
      phase or under certain stress conditions, these TAG are generally made of
      saturated and monounsaturated fatty acids. In contrast, most cellular AA of P.
      incisa resides in TAG. Using various inhibitors, we have attempted to find out if
      the induction of the biosynthesis of AA and the accumulation of TAG are
      codependent. Salicylhydroxamic acid (SHAM) affected a growth reduction that was
      accompanied with an increase in the content of TAG from 3.0 to 6.2% of dry
      weight. The proportion of 18:1 increased sharply in all lipids while that of 18:2
      and its down stream products, 18:3omega6, 20:3omega6 and AA, decreased,
      indicating an inhibition of the Delta12 desaturation of 18:1. Treatment with the
      herbicide SAN 9785 significantly reduced the proportion of TAG. However, the
      proportion of AA in TAG, as well as in the polar lipids, increased. These
      findings indicate that while there is a preference for AA as a building block of
      TAG, the latter can be produced using other fatty acids, when the production of
      AA is inhibited. On the other hand, inhibiting TAG construction did not affect
      the production of AA. In order to elucidate the possible role of AA in TAG we
      have labeled exponential cultures of P. incisa kept at 25 degrees C with [1
      14C]arachidonic acid and cultivated the cultures for another 12 h at 25, 12 or 4
      degrees C. At the lower temperatures, labeled AA was transferred from TAG to
      polar lipids, indicating that TAG of P. incisa may have a role as a depot of AA
      that can be incorporated into the membranes, enabling the organism to quickly
      respond to low temperature-induced stress.

PMID- 12009317
TI  - Integration of ethnobotany and phytochemistry. dream or reality?
AB  - The major challenge of this paper comprises an attempt to compare the wealth of
      folk-information based on "traditional knowledge" with the efficacy of a chemo
      biological background based on scientific knowledge. Surprisingly, correlations
      between plant uses (as food and medicine) and evolutionary status according to
      morphology (as assigned by Sporne indices) and metabolism (as assigned by
      diversity of phytochemicals) obey strikingly uniform systematic and evolutionary
      trends. The resulting patterns suggest a dynamic chemical mechanism for the
      bioactivity in plants regulated by the antagonistic gallate/caffeate pair. This
      finding is an important step toward the construction of a coherent chemo
      biological language by a dynamic holistic quantitative methodology, one of the
      most potent prospects for understanding the functioning of nature.

PMID- 12009318
TI  - Accumulation and detoxification of lead ions in legumes.
AB  - This study focuses on lead accumulation in roots, stems and leaves of three plant
      species of the Fabacea family: Vicia faba, Pisum sativum and Phaseolus vulgaris
      grown hydroponically in a medium supplemented with 1 mM concentration of lead.
      The largest amount of lead, up to 75 mg Pb/g dry weight, was accumulated in roots
      of P. vulgaris. The highest rate of Pb ions uptake from the medium took place
      during the first 10 h of incubation with lead and after 96 h of incubation lead
      content in the medium decreased by half. Thus, it was suggested that P. vulgaris
      could be used in rhizofiltration--the use of plant roots to absorb pollutants
      from water contaminated with lead. At the same time we studied the influence of
      lead on acid soluble thiol, glutathione, homoglutathione contents and the
      synthesis of phyto- and homophytochelatins in roots of V. faba, P. sativum and P.
      vulgaris grown hydroponically. Activation of the detoxicative-phytochelatin
      system was observed in the cytosol of root cells of the tested plants. This
      system was composed of phytochelatins (PCs) in roots of V. faba,
      homophytochelatins (hPCs) in P. vulgaris roots and both PCs and hPCs in P.
      sativum roots. The total content of PCs and hPCs in roots of P. sativum was very
      high and reached around 4800 (expressed in nmol SH x g(-1)FW) and induction of
      their synthesis occurred after only 2 h of treatment with 1 mM Pb.

PMID- 12009319
TI  - Antifeedant activity of an anthraquinone aldehyde in Galium aparine L. against
      Spodoptera litura F.
AB  - The insect antifeedant anthraquinone aldehyde nordamnacanthal (1,3-dihydroxy
      anthraquinone-2-al) was identified in Galium aparine L., and isolated from the
      root powder of akane (Rubia akane), a member of the Rubiaceae. Structure-activity
      relationship (SAR) studies using a series of anthraquinone analogues suggested
      that the aldehyde group on the anthraquinone was more important than the quinone
      moiety for antifeedant activity against the common cutworm (Spodoptera litura).
      High levels of nordamnacanthal were found in the seed leaf stage and in callus
      tissue induced from seedlings of G. aparine, but its concentration decreased with
      plant development. Since these compounds are natural pigments for dying textiles,
      we also evaluated the antifeedant activity against the carpet beetle (Attagenus
      japonicus ), a textile pest was also evaluated. While nordamnacanthal had strong
      antifeedant activity against the common cutworm, it did not show any antifeedant
      activity against the carpet beetle. The most effective antifeedant against the
      carpet beetle was the major constituent in the extract of R. trictorum, lucidin-3
      O-primeveroside, a food pigment.

PMID- 12009320
TI  - Antiplasmodial activity of sesquilignans and sesquineolignans from Bonamia
      spectabilis.
AB  - Phytochemical re-investigation of the aerial parts of Bonamia spectabilis
      (Convolvulaceae) led to the isolation of four minor tetrahydrofuran-type
      sesquilignans (bonaspectins E-H) together with the known neolignan virolongin A
      and the known lignan rel-(7S,8R,7'R,8'R)-3,3',4,4',5,5'-hexamethoxylignan. Their
      structures were established on the basis of spectral data. These six compounds as
      well as further seven lignanoids from B. spectabilis, characterised previously,
      were tested for their antiplasmodial activity against a chloroquine-sensitive
      strain (PoW) and a chloroquine-resistant clone (Dd2) of Plasmodium falciparum.
      Bonaspectin C 4"-O-glucoside, its aglycone, and bonaspectin D 4"-O-glucoside
      revealed the highest antiplasmodial activities (IC50 values: 1.3, 2.0, 6.5 microM
      [PoW]; 1.7, 4.6, 3.7 microM [Dd2], respectively).

PMID- 12009321
TI  - Spermine alkaloids from Albizia adinocephala with activity against Plasmodium
      falciparum plasmepsin II.
AB  - Crude MeOH extracts from the stem bark and leaves of a Panamanian specimen of
      Albizia adinocephala (Leguminosae) were found to inhibit the malarial enzyme
      plasmepsin II. Bioassay guided fractionation led to the isolation of two new
      bioactive spermine alkaloids, budmunchiamines L4 and L5.

PMID- 12009322
TI  - Isopestacin, an isobenzofuranone from Pestalotiopsis microspora, possessing
      antifungal and antioxidant activities.
AB  - Isopestacin is an isobenzofuranone obtained from the endophytic fungus
      Pestalotiopsis microspora. While a few other isobenzofuranones are known from
      natural sources, isopestacin is the only one having a substituted benzene ring
      attached at the C-3 position of the furanone ring. The compound was isolated from
      culture broths of the fungus and crystallized and its structure was determined by
      X-ray crystallography. Both proton and carbon NMR spectral assignments are also
      reported for isopestacin. This compound possesses antifungal activity and, as
      measured by electron spin resonance specroscopy, it also behaves as an
      antioxidant scavenging both superoxide and hydroxy free radicals.

PMID- 12009323
TI  - Triterpenoid saponins from Oreopanax guatemalensis.
AB  - Seven oleanane-type saponins were isolated from the leaves and stems of Oreopanax
      guatemalensis, together with ten known saponins of lupane and oleanane types. The
      new saponins were respectively characterized as 3-O-alpha-L-arabinopyranosyl
      echinocystic acid 28-O-[alpha- L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1
      ->6)-beta-D-glucopyranosyl] ester, 3-O-beta-D-glucopyranosyl 3beta-hydroxy olean
      11,13(18)-dien-28-oic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->6)-beta- D-glucopyranosyl]ester, 3-O-[alpha-L-rhamnopyranosyl
      (1-->2)-beta-D-glucopyranosyl]3beta-hydroxy olean-11,13(18)-dien-28-oic acid 28-O
      [alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl] ester, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl]3beta, 23 dihydroxy olean-18-en-28-oic acid 28-O-[alpha-L
      rhamnopyranosyl-(1-->4)-beta-D-6-O-acetyl glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl]ester, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl] hederagenin 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->6)-[beta-D-xylopyranosyl-(1-->2 )-]beta-D
      glucopyranosyl]ester, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl]hederagenin 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->6)-[beta-D-glucopyranosyl-(1-->2)-]beta-D-glucopyranosyl]
      ester and 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl]
      hederagenin 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)
      [alpha-L-arabinofuranosyl-(1-->2)]-beta-D-glucopyranosyl] ester. The structures
      were determined by spectral analyses. The NMR assignments were made by means of
      HOHAHA, 1H-1H COSY, HMQC, HMBC spectra and NOE difference studies.

PMID- 12009324
TI  - Three labdane diterpenoids from Aframomum sceptrum (Zingiberaceae).
AB  - Three labdane diterpenoids, 8beta,17-epoxy-3beta,7beta-dihydroxy-12(E)-labden
      16,15-olide (1), methyl 8beta,17-epoxy-3beta,7beta,15-trihydroxy-12(E)-labden-16
      oate (2) and 3beta,7beta,8beta,12zeta,17-pentahydroxylabdan-16,15-olide (3) have
      been isolated from the seeds of Afromomum sceptrum K. Schum (Zingiberaceae) and
      their structures assigned on the basis of their spectroscopic properties.
      Nerolidol, and the known flavonoids 3-acetoxy-4',5,7-trihydroxyflavanone, and
      3,4',5,7-tetrahydroxyflavanone were also obtained.

PMID- 12009327
TI  - From the editor's desk.

PMID- 12009328
TI  - The NH(2)-terminal propeptides of fibrillar collagens: highly conserved domains
      with poorly understood functions.
AB  - The impetus for this review comes from the recent finding that the absence of the
      majority of the non-triple-helical sequence in the NH(2)-terminal propeptide (N
      propeptide) of the pro alpha 1(I) collagen chain fails to generate a significant
      phenotype in the mouse (Bornstein et al., J. Biol. Chem., 277:2605-2613, 2002).
      This result is in apparent conflict with those of numerous studies in vitro that
      have implicated the N-propeptide in a number of processes that are involved in
      the biogenesis, maturation and function of type 1 collagen. To seek an
      explanation for this discrepancy, the sequences of the highly conserved, 55-57
      amino acid, cysteine-rich repeats (CRR), which constitute the majority of the
      globular domains in the N-propeptides, were compared among 13 vertebrate species.
      Surprisingly, the CRR in mice and rats differs substantially from those in other
      mammalian species. Indeed, the CRR in birds, fish and amphibia are more similar
      to those of other mammals than are the CRR in rodents. This finding raises the
      possibility that the mutant mouse, which lacks exon 2 that encodes the CRR in the
      N-propeptide, might not be an appropriate model in which to study the function of
      the N-propeptide in other mammals. Alternatively, compensation, possibly by
      procollagens II or III, could account for the mild phenotype of the exon 2
      deleted mouse. Yet another possibility is that the CRR plays a developmental role
      in the mouse, akin to that recently proposed for the N-propeptide in type IIA
      procollagen, rather than a function in collagen biogenesis. Some support for the
      latter possibility is provided by the observation that, on one background, the
      breeding of heterozygous exon 2-deleted mice generated homozygous mutants at less
      than the expected frequency. Experiments to examine these possibilities are
      proposed.

PMID- 12009329
TI  - Alternative splicing of transcripts for the alpha 3 chain of mouse collagen VI:
      identification of an abundant isoform lacking domains N7-N10 in mouse and human.
AB  - Three distinct alpha chains form the collagen VI monomer, the alpha 3(VI) chain
      being much larger than the alpha 1(VI) and alpha 2(VI) chains. The alpha 3(VI)
      chain has 10 von Willebrand Factor type A domains of approximately 200 amino
      acids at the N-terminus (N1-N10) compared with only one such domain in the alpha
      1(VI) and alpha 2(VI) chains. Domains N10, N9, N7 and N3 of the alpha 3(VI) chain
      are subject to alternative splicing in chick and/or human tissues, indicating the
      possibility of isoforms that have different functions depending on which N
      terminal domains are included or excluded. In this study we have PCR amplified
      and sequenced mouse alpha 3(VI) cDNA encoding the N2-N10 domains. By reverse
      transcription-PCR using oligonucleotides spanning different regions of the cDNA
      we have undertaken a comprehensive analysis of alternative splicing of the alpha
      3(VI) mRNA in embryonic and adult mouse tissues. We demonstrate that domains N10,
      N9 and N7 are also subject to alternative splicing in mouse tissues and in
      addition identify an abundant novel variant transcript that lacks all four N
      terminal domains (N7-N10) in mouse tissues and human cells. We also identify less
      abundant transcripts that lack a large part of the N3 domain, and transcripts
      lacking the entire N5 domain. Using specific RNase protection assays we show that
      the shorter transcripts containing domains (N8+N7+N6), (N8+N6) and N6 are present
      at higher levels than transcripts containing the N10 and/or N9 domains, with
      tissue-specific variation in the levels of variant transcripts. These studies
      demonstrate a larger range of collagen VI protein variants than previously
      described.

PMID- 12009330
TI  - TGF-beta alters collagen XII and XIV mRNA levels in cultured equine tenocytes.
AB  - The effects of TGF-beta 1, beta 2 and beta 3 (TGF-beta) on levels of mRNA
      corresponding to the alpha chains of type XII and type XIV collagens in equine
      tenocyte cultures were assessed using the ribonuclease protection assay (RPA).
      The level of alpha1(XII) mRNA in untreated monolayer cultures was approximately
      50- to 100-fold greater than alpha1(XIV) mRNA level. Addition of TGF-beta
      resulted in an increase in the amount of alpha1(XII) present and a decrease of
      alpha1(XIV) mRNA in a dose-dependent manner. Specifically, the level of
      alpha1(XII) mRNA was doubled, but alpha1(XIV) was decreased to 30% of control by
      the addition of 2 ng/ml of TGF-beta 1 to the cultures. These effects were
      completely abrogated by neutralizing antibody specific for TGF-beta. In addition,
      electron microscopy demonstrated that bundled collagen fibers were formed in the
      intercellular spaces of multilayered tenocytes which had been cultured for 2
      weeks in the presence of exogenous TGF-beta 1 together with ascorbic acid
      phosphate. These results suggest that type XII and/or type XIV collagens modulate
      the structure of ECM formed by tenocytes in culture.

PMID- 12009331
TI  - Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1)
      and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates
      matrix metalloproteinase gene expression in articular chondrocytes.
AB  - Interleukin-1 (IL-1), the main cytokine instigator of cartilage degeneration in
      arthritis, induces matrix metalloproteinase-3 (MMP-3) and MMP-13 RNA and protein
      in chondrocytes. The molecular mechanisms of this induction were investigated
      with specific inhibitors of mitogen-activated protein kinase (MAPK) signaling
      pathways and activating protein (AP-1) and nuclear factor kappa B (NF-kappa B)
      transcription factors. IL-1 rapidly induced the activation of extracellular
      signal regulated kinase (ERK), protein 38 (p38) and c-Jun N-terminal kinase (JNK)
      MAPKs in the first-passage human femoral head OA chondrocytes. The ERK-MAPK
      pathway inhibitor, PD98059, attained 46-53% (MMP-3) and 59-66% (MMP-13)
      inhibition of RNA induction in human OA and 47-52% (MMP-3) and 69-73% (MMP-13)
      inhibition in bovine chondrocytes. U0126 conferred 37-77% (MMP-3) and 43-73% (MMP
      13) suppression in human and 77-100% (MMP-3) and 96-100% (MMP-13) in bovine
      chondrocytes. P38 and JNK inhibitor, SB203580 caused 35-37% reduction of MMP-3
      and MMP-13 RNA in human and 36-46% (MMP-3) and 60-88% (MMP-13) in bovine
      chondrocytes. Inhibitor of JNK, AP-1 and NF-kappa B, curcumin, achieved 48-99%
      suppression of MMP-3 and 45-97% of MMP-13 in human and 8-100% (MMP-3) and 32-100%
      (MMP-13) in bovine chondrocytes. NF-kappaB inhibitor, pyrrolidine dithiocarbamate
      yielded 83-84% reduction of MMP-3 and 38-55% for MMP-13 in human chondrocytes. In
      bovine chondrocytes, the induction decreased by 54-64% for MMP-3 and 74-93% for
      MMP-13 RNA. These results suggest the involvement of MAPKs, AP-1 and NF-kappa B
      transcription factors in the IL-1 induction of MMPs in chondrocytes. Inhibition
      of IL-1 signal transduction by these agents could be useful for reducing
      cartilage resorption by MMPs in arthritis.

PMID- 12009332
TI  - Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by
      mechanical strain in MH7A rheumatoid synovial cells.
AB  - Excessive mechanical load induces harmful outcomes for joint diseases, such as
      osteoarthritis and rheumatoid arthritis, but physical stimuli at appropriate
      intensity are essential for growth and maintenance of bone and articular
      cartilage. Using a fibroblast-like synoviocyte cell line derived from a patient
      with rheumatoid arthritis, we examined the effects of gentle cyclic strain,
      focusing on the expression and activity of matrix metalloproteinase-1 (MMP-1) and
      MMP-13. Synovial cells were cultured on a collagen-coated agar block and exposed
      to 2% cyclic strain at 6 rev./min for 1 h. Expression of MMP-1 and MMP-13 was
      assayed using semi-quantitative and real-time PCR, as well as immunoblotting.
      Their activity was measured using spectrofluorometry and zymography. The results
      showed that the cyclic strain reduced the mRNA and protein levels of MMP-1 and
      MMP-13, and that both collagenase and gelatinase activity was decreased under the
      strain. The reduction in MMP activity by the cyclic strain was not achieved by
      the transcriptional inhibitor, actinomycin D. In the presence of proinflammatory
      cytokines, such as IL-1 beta and TNF-alpha, the strain reduced the cytokine
      induced expression and activities of MMPs. Interestingly, the strain elevated the
      mRNA level of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. These
      results support a potential role of mechanical strain in down-regulating the
      cytokine-mediated proteolytic processes in synoviocytes.

PMID- 12009333
TI  - Matrix metalloproteinases are involved in C-terminal and interglobular domain
      processing of cartilage aggrecan in late stage cartilage degradation.
AB  - Monoclonal antibody (MAb) technology was used to examine aggrecan metabolites and
      the role of aggrecanases and matrix metalloproteinases (MMPs) in proteolysis of
      the interglobular domain (IGD) and C-terminus of aggrecan. An in vitro model of
      progressive cartilage degradation characterized by early proteoglycan loss and
      late stage collagen catabolism was evaluated in conjunction with a broad-spectrum
      inhibitor of MMPs. We have for the first time demonstrated that IGD cleavage by
      MMPs occurs during this late stage cartilage degeneration, both as a primary
      event in association with glycosaminoglycan (GAG) release from the tissue and
      secondarily in trimming of aggrecanase-generated G1 metabolites. Additionally, we
      have shown that MMPs were responsible for C-terminal catabolism of aggrecan and
      generation of chondroitin sulfate (CS) deficient aggrecan monomers and that this
      aggrecan truncation occurred prior to detectable IGD cleavage by MMPs. The onset
      of this later stage MMP activity was also evident by the generation of MMP
      specific link protein catabolites in this model culture system. Recombinant MMP
      1, -3 and -13 were all capable of C-terminally truncating aggrecan with at least
      two cleavage sites N-terminal to the CS attachment domains of aggrecan. Through
      analysis of aggrecan metabolites in pathological synovial fluids from human,
      canine and equine sources, we have demonstrated the presence of aggrecan
      catabolites that appear to have resulted from similar C-terminal processing of
      aggrecan as that induced in our in vitro culture systems. Finally, by developing
      a new MAb recognizing a linear epitope in the IGD of aggrecan, we have identified
      two novel aggrecan metabolites generated by an as yet unidentified proteolytic
      event. Collectively, these results suggest that C-terminal processing of aggrecan
      by MMPs may contribute to the depletion of cartilage GAG that leads to loss of
      tissue function in aging and disease. Furthermore, analysis of aggrecan
      metabolites resulting from both C-terminal and IGD cleavage by MMPs may prove
      useful in monitoring different stages in the progression of cartilage
      degeneration.

PMID- 12009334
TI  - Expression of matrilins during maturation of mouse skeletal tissues.
AB  - The matrilins are a recently discovered family of non-collagenous extracellular
      matrix proteins. During embryogenesis, all matrilins are expressed in skeletal
      tissues. Additionally, matrilin-2 and -4 are expressed in the dermis and in
      connective tissues of internal organs, e.g. of the lung and kidney. After birth,
      the expression of matrilin-1 and -3 remains specific for cartilage and bone
      whereas matrilin-2 and -4 display a broader tissue distribution and could be
      detected in epithelial, muscle, and nervous tissue as well as in loose and dense
      connective tissue. In epiphyseal cartilage of growing long bones, matrilin-1 and 
      3 are present in all cartilage regions, in contrast to matrilin-2, which is
      expressed in the proliferative and the upper hypertrophic zones. Similarly
      matrilin-4 was detected all over the epiphyseal cartilage, with the weakest
      expression in the hypertrophic zone. Although it was shown that matrilin-1 and -3
      can form hetero-oligomers and are often co-localized in tissue, clear differences
      in their spatial distribution could be demonstrated by double-immunolabelling.
      During joint development matrilin-2 and matrilin-4 are present at the developing
      joint surface, while in articular cartilage of 6-week-old mice all matrilins are
      only weakly expressed.

PMID- 12009335
TI  - Expression of integrin beta 6 enhances invasive behavior in oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinoma (SCC) is characterized by invasive growth and the
      propensity for distant metastasis. The expression of specific adhesion receptors
      promotes defined interactions with the specific components found within the
      extracellular matrix (ECM). We previously showed that the alpha v beta 6
      fibronectin receptor is highly expressed in oral SCC. Here we forced expression
      of the beta 6 subunit into poorly invasive SCC9 cells to establish the SCC9 beta
      6 cell line and compared these two cell lines in several independent assays.
      Whereas adhesion to fibronectin was unaffected by the expression of beta 6,
      migration on fibronectin and invasion through a reconstituted basement membrane
      (RBM) were both increased. Function-blocking antibodies to alpha v beta 6 (10D5)
      reduced both migration on fibronectin and invasion through an RBM, whereas anti
      alpha 5 antibodies were effective only in suppressing migration on fibronectin,
      not invasion. Expression of beta 6 also promoted tumor growth and invasion in
      vivo and modulated fibronectin matrix deposition. When grown as a co-culture with
      SCC9 cells, peritumor fibroblasts (PTF) organized a dense fibronectin matrix.
      However, fibronectin matrix assembly was decreased in co-cultures of SCC9 beta 6
      cells and PTF and this decrease was reversed by the addition of function-blocking
      anti-alpha v beta 6 antibodies. The expression of beta 6 also resulted in
      increased levels of matrix metalloproteinase 3. Addition of the general MMP
      inhibitor GM6001 to SCC9 beta 6/PTF co-cultures dramatically increased
      fibronectin matrix assembly in a similar fashion as incubation with anti-alpha v
      beta 6 antibodies. These results demonstrate that expression of beta 6 (1)
      increases oral SCC cell motility and growth in vitro and in vivo; (2) negatively
      affects fibronectin matrix assembly; and (3) stimulates the expression and
      activation of MMP3. We suggest that the integrin alpha v beta 6 is a key
      component of oral SCC invasion and metastasis through modulation of MMP-3
      activity.

PMID- 12009336
TI  - Oxidative stress and peritoneal endometriosis.
AB  - OBJECTIVE: To review the literature associating pelvic endometriosis with
      oxidative stress and to discuss the potential causes and consequences of a pro
      oxidant environment in the peritoneal cavity. DESIGN: Literature survey.
      RESULT(S): Several studies suggest that oxidative stress is a component of the
      inflammatory reaction associated with endometriosis. Evidence includes the
      prevention of endometriosis induction in rabbits by the addition of antioxidants,
      an increase in reactive oxygen species release by macrophages, increased
      peritoneal levels of oxidized low-density lipoproteins and their by-products,
      altered expression of endometrial pro-oxidant and antioxidant enzymes, and
      consumption of peritoneal fluid vitamin E. Retrograde menstruation is likely to
      carry highly pro-oxidant factors, such as heme and iron, into the peritoneal
      cavity, as well as apoptotic endometrial cells, which are well-known inducers of
      oxidative stress. Reactive oxygen species may be involved in endometriosis
      associated infertility and may play a role in the regulation of the expression of
      genes encoding immunoregulators, cytokines and cell adhesion molecules implicated
      in the pathogenesis of endometriosis. CONCLUSION(S): Better understanding of the
      mechanisms of reactive oxygen species production and detoxification and further
      investigation of their effect on the peritoneal environment are essential to
      obtain new insight into this disease and eventually develop new diagnostic and
      therapeutic strategies.

PMID- 12009337
TI  - Manuscript submissions to the journal: American sterility, foreign fertility?

PMID- 12009338
TI  - Best practice policies for male infertility.

PMID- 12009339
TI  - Ethical issues in biomedical publications.
AB  - Peer-reviewed biomedical journals are expected to publish accurate and important
      information. In the process, numerous ethical issues may arise from within both
      the editorial and research communities. This paper will focus on four general
      ethical issues-authorship, peer review, duplicate or repetitive publication, and
      conflict of interest. Issues of authorship include multiple authorship,
      misconduct among coauthors, guest and honorary authorship, order of authorship,
      and credit for those not qualifying for authorship. Peer review attempts to
      ensure that what is published is valid. Peer review ethical issues include
      confidentiality of the manuscript, potential editor and reviewer bias, and
      conflict of interest on the part of the reviewer. Duplicate or repetitive
      publication, in which the same information is reported two or more times, can
      damage a journal's reputation for publishing new and important information and
      can waste its resources. Conflicts of interest, in which financial and personal
      considerations may affect the investigator's personal judgment, can seriously
      damage the integrity of the author and of the journal. Increased awareness of
      these ethical issues should stimulate everyone to take an active role in
      promulgating and enforcing the highest ethical standards in biomedical
      publications.

PMID- 12009340
TI  - Relation between the anatomical genital phenotype and cystic fibrosis
      transmembrane conductance regulator gene mutations in the absence of the vas
      deferens.
AB  - OBJECTIVE: To study the correlation between genital phenotype and cystic fibrosis
      genotype in men lacking at least one vas deferens. DESIGN: Prospective study.
      SETTING: Institut Rhonalpin pour la Reproduction Humaine, Lyon-Bron, France.
      PATIENT(S): Forty-seven infertile men lacking at least one vas deferens.
      INTERVENTION(S): All patients were screened for the 13 most common CFTR gene
      mutations and for the 5-thymidine variant of intron 8. Renal, scrotal, and
      transrectal ultrasonography were systematically performed. MAIN OUTCOME
      MEASURE(S): Epididymal and seminal vesicular abnormalities and testicular volume
      were compared among men with two, one, or no CFTR gene mutation, with or without
      the 5T allele. RESULTS: Seminal vesicles and the symmetry of epididymal and
      vesicular abnormalities did not differ between patients with and those without
      the CFTR gene mutation. Epididymal abnormalities were more frequent in men
      without the mutation. Testicular volumes were significantly lower in men without
      the mutation and those with the 5T allele only. CONCLUSION: Men with the CFTR
      mutation, the 5T allele only, and those without CFTR mutation have few
      differences in genital phenotype. Low testicular volume is observed in men
      without the CFTR mutation and those with the 5T allele only.

PMID- 12009341
TI  - Gene-based screening for Y chromosome deletions in Taiwanese men presenting with
      spermatogenic failure.
AB  - OBJECTIVE: To develop a simple and rapid protocol for detecting deletions of the
      Y chromosome and to evaluate the feasibility of gene-based screening in men with
      spermatogenic failure. DESIGN: Prospective case study. SETTING: University-based
      reproductive clinics and genetics laboratory. PATIENT(S): Two hundred two
      infertile men presenting with severe oligozoospermia and nonobstructive
      azoospermia. INTERVENTION(S): Fifteen gene-specific primers were used to detect
      deletions of Y chromosome genes in men with spermatogenic failure. A multiplex
      polymerase chain reaction amplification system was developed to facilitate rapid
      screening. Another 24 markers for sequence-tagged sites (STS) were used to ensure
      the adequacy of gene-based screening. MAIN OUTCOME MEASURE(S): Detection of
      deletions of Y chromosome genes. RESULT(S): Of 180 patients evaluated, 19 (10.6%)
      had deletions of one or more genes, including DFFRY, DBY, RBM1, DAZ, CDY1, and
      BPY2. A second round of STS-based screenings did not show an increase in the
      deletion rate but more clearly defined the extent of deletion in 14 of the 19
      patients. In most patients, deletions detected by gene-based screening were
      similar to those detected by STS markers. CONCLUSION(S): Gene-based screening
      with multiplex polymerase chain reaction is a rational alternative for detecting
      deletions of Y chromosome genes in infertile men.

PMID- 12009342
TI  - Sertoli cell maturation in men with azoospermia of different etiologies.
AB  - OBJECTIVE: To evaluate the involvement of Sertoli cell in different spermatogenic
      disorders. DESIGN: Retrospective case-control study. SETTING: Teaching hospital.
      PATIENT(S): Azoospermic men who underwent testicular biopsy for sperm recovery in
      preparation for intracytoplasmic sperm injection. INTERVENTION(S): Testicular
      biopsy evaluation by quantitative immunohistochemistry for the immature Sertoli
      cell markers anti-Mullerian hormone and cytokeratin 18 (CK-18). MAIN OUTCOME
      MEASURE(S): Relative area of immature Sertoli cells in testes with focal
      spermatogenesis, spermatocyte maturation arrest, or normal spermatogenesis.
      RESULT(S): The relative area occupied by immature Sertoli cells, as revealed by
      anti-Mullerian hormone and CK-18 expression, was highest in the 11 men with focal
      spermatogenesis. In the group representing normal spermatogenesis (obstructive
      azoospermia, 6 men) and in the group characterized by spermatocyte maturation
      arrest (6 men), the areas occupied by anti-Mullerian hormone- and CK-18-positive
      cells were minimal. CONCLUSION(S): Different etiologies underlie the
      spermatogenic disorders reported in this study. In focal spermatogenesis with
      high anti-Mullerian hormone and CK-18 expression, the spermatogenic impairment is
      associated with the presence of immature Sertoli cells. The detection of normal
      mature Sertoli cells in the spermatocyte maturation arrest group indicates that
      the spermatogenic defect that is accompanied by an impairment of meiosis is
      intrinsic to the germ line without affecting Sertoli cell differentiation.

PMID- 12009343
TI  - Sperm maturity and treatment choice of in vitro fertilization (IVF) or
      intracytoplasmic sperm injection: diminished sperm HspA2 chaperone levels predict
      IVF failure.
AB  - OBJECTIVE: To reexamine whether low sperm HspA2 ratios (formerly sperm CK-M
      ratio) are predictive for failure to cause pregnancies by in vitro fertilization
      (IVF) and to explore whether there are other male or female factors that may be
      predictive for IVF pregnancy outcome. DESIGN: Retrospective, cohort study.
      SETTING: University-based IVF program. PATIENT(S): In 119 IVF cycles, three
      patient groups were studied: 25 men had a <10% sperm HspA2 ratio and a lack of
      pregnancies (HS <10% group), 50 men had a >10% sperm HspA2 ratio and no
      pregnancies (HS >10%NP group), and another 44 couples had a >10% sperm HspA2
      ratio but did achieve pregnancies (HS >10%P group). INTERVENTION(S): Sperm HspA2
      ratio determinations within 1 year of the IVF cycles and analysis of male and
      female IVF cycle parameters. MAIN OUTCOME MEASURE(S): Sperm HspA2 ratio
      determinations within 1 year of the IVF cycles and analysis of male and female
      IVF cycle parameters. RESULT(S): In the three groups, male and female ages,
      number and maturation level of oocytes, and morphology of embryos were similar.
      In the HS < 10% group, mean sperm concentration and motility were close to
      normal, the fertilization and cleavage rates were lower, and cycles without any
      oocyte fertilization were higher. These parameters were similar in the two HS >
      10% groups. The receiver operating characteristic curve in men with sperm HspA2
      ratios of <17% (diminished and borderline sperm maturity) provided a cutoff value
      of 10.84% HspA2 ratio with a 100% positive predictive value for failure to
      achieve pregnancy, whether the men were oligospermic or normospermic.
      CONCLUSION(S): HspA2 ratios of <10% in the diminished sperm maturity range
      predict the failure to cause pregnancies by IVF. Thus, IVF should be bypassed in
      favor of ICSI. The occurrence of pregnancy with ICSI depends on the maturity of
      sperm selected, and it may not be as likely as in other indications for ICSI.

PMID- 12009344
TI  - Androgen and lipid profiles in adolescents with polycystic ovary syndrome who
      were treated with two forms of combined oral contraceptives.
AB  - OBJECTIVE: To compare the effects of cyproterone acetate and desogestrel, as part
      of combined oral contraceptives, on lipid metabolism and hirsutism of adolescents
      with polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized clinical
      trial. SETTING: Outpatient gynecology clinic (referral center) of a university.
      PATIENT(S): Twenty-eight adolescent girls with clinical and biological
      hyperandrogenism and six or less menses during the past 12 months.
      INTERVENTION(S): Group A (n = 14) received 0.15 mg of desogestrel plus 0.030 mg
      of ethinyl estradiol daily. Group B (n = 14) received 2 mg of cyproterone acetate
      plus 0.035 mg of ethinyl estradiol daily. Treatment was given for 21 days
      followed by a 7-day rest for a period of 12 months. MAIN OUTCOME MEASURE(S):
      Hirsutism and lipid profile were evaluated before initiation and at 3, 6, 9, and
      12 months of treatment. Androgen profile was evaluated before and at 12 months of
      treatment. RESULT(S): A significant decline of the Ferriman-Gallway hirsutism
      score was observed from the sixth month of therapy in both groups. During
      therapy, the levels of testosterone, free testosterone, Delta(4)-androstenedione,
      and 17OH-progesterone decreased significantly, whereas sex hormone-binding
      globulin (SHBG) increased significantly in both groups. The level of total
      cholesterol and low density lipoprotein (LDL) cholesterol increased
      significantly, whereas high density lipoprotein (HDL) cholesterol and
      apolipoprotein A-I increased significantly from the third month of therapy in
      both groups. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL
      cholesterol ratios remained unchanged. The levels of triglycerides increased
      significantly in the cyproterone acetate-treated group after the third month.
      CONCLUSION(S): Treatment of adolescent girls with PCOS with the two studied
      formulations is comparably effective in decreasing hirsutism and androgen levels.
      Both combined oral contraceptives are associated with an increase of total
      cholesterol, LDL cholesterol, and HDL cholesterol levels and no change of the
      total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios.
      Treatment with the cyproterone acetate combined oral contraceptive is associated
      with a tendency toward increasing the levels of triglycerides.

PMID- 12009345
TI  - Polycystic ovarian morphology and bulimia nervosa: a 9-year follow-up study.
AB  - OBJECTIVE: To examine long-term changes in polycystic ovarian morphology in women
      with polycystic ovaries and bulimia nervosa after treatment of the latter
      condition. DESIGN: Longitudinal follow-up study. SETTING: Eating disorder unit of
      a university hospital. PATIENT(S): Eight women originally treated for bulimia
      nervosa (T(0)) who underwent ultrasonography up to 2 years after treatment (T(1))
      and had a second ultrasonographic scan 9 years later (T(2)). INTERVENTION(S):
      Treatment of bulimia nervosa that combined cognitive behavioral therapy with
      insight-orientated psychotherapy. MAIN OUTCOME MEASURE(S): Ovarian morphology
      evaluated by ultrasonography, using the criteria of Adams to define polycystic
      ovaries; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      diagnosis of eating disorders. RESULT(S): At T(1), 7 women had recent bulimia and
      1 was quiescent. The woman with quiescent disease had normal ovaries. Of the 7
      bulimic women, 6 had polycystic ovaries and 1 had multifollicular morphology. At
      T(2), 5 women were bulimic, all of whom had polycystic ovaries. Three women had
      normal eating patterns and normal ovarian morphology. CONCLUSION(S): This study
      clearly shows a strong association between resolution of bulimia and changes in
      ovarian morphology, suggesting that changes in the former mirror changes in the
      latter. It also demonstrates normalization of ovarian morphology in previously
      polycystic ovaries.

PMID- 12009346
TI  - Serum leptin levels in patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether polycystic ovary syndrome (PCOS) is related to
      leptin dysregulation. DESIGN: Prospective study. SETTING: Department of
      Obstetrics and Gynecology in a university hospital. PATIENT(S): Fifty patients
      with PCOS (33 nonobese and 17 obese) and 32 control women (19 nonobese and 13
      obese) were included in the study. INTERVENTION(S): Serum leptin levels were
      measured in patients with PCOS and the controls. Correlations between leptin
      levels and serum hormone levels (FSH, LH, free testosterone, androstenedione,
      DHEA-S and fasting insulin) were studied. MAIN OUTCOME MEASURE(S): Serum leptin
      levels and correlations between leptin levels and the hormonal parameters.
      RESULT(S): Mean serum leptin levels were not significantly higher in patients
      with PCOS compared to the control group. Leptin levels were found to be
      significantly higher in the obese subgroups both in patients with PCOS and in the
      control women. Leptin levels were found to be higher in obese patients with PCOS
      compared to obese controls; however, when the levels were evaluated again with
      covariance analysis excluding body mass index, there was no statistically
      significant difference. Leptin levels had a positive correlation with body mass
      index, both in patients with PCOS and the controls. CONCLUSION(S): Leptin levels
      were not higher in patients with PCOS compared to the control group; the leptin
      level was correlated with the amount of fat tissue not only in patients with PCOS
      but also in healthy women.

PMID- 12009347
TI  - Effect of long-term naltrexone treatment on endocrine profile, clinical features,
      and insulin sensitivity in obese women with polycystic ovary syndrome.
AB  - OBJECTIVE: Evaluation of clinical and endocrine effects of naltrexone
      administration in obese women with PCOS. DESIGN: Open, controlled, clinical
      study. SETTING: Department of Reproductive Medicine and Child Development,
      Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
      PATIENT(S): Ten PCOS women were studied. INTERVENTION(S): Women were treated with
      naltrexone (50 mg/day) for 6 months. MAIN OUTCOME MEASURE(S): Body mass index and
      the menstrual cyclicity during naltrexone treatment were assessed. Basal levels
      of LH, FSH, 17beta-estradiol (E(2)), 17-hydroxyprogesterone, total and free T,
      androstenedione, dehydroepiandrosterone sulfate, cortisol, sex hormone-binding
      globulin were evaluated before treatment and every 3 months. Progesterone levels
      were measured in the luteal phase during the sixth month. Gonadotropin response
      to GnRH administration (10 microg) and a 75-g oral glucose tolerance test were
      performed before and every 3 months. RESULT(S): Body mass index significantly
      decreased from 29.94 +/- 1.04 to 26.07 +/- 0.81 during treatment. The menstrual
      cyclicity improved in 80% of PCOS women: the mean cycle length was 40-360 days
      before treatment and ranged between 25 and 120 days and 28-120 days after 3 and 6
      months of treatment. Plasma levels of free T, androstenedione,
      dehydroepiandrosterone sulfate, and cortisol significantly decreased. Fasting
      glucose-to-insulin ratio improved in women with insulin resistance.
      CONCLUSION(S): Naltrexone may have a beneficial effect on the clinical and
      endocrine-metabolic disturbances of obese PCOS women. Whether these effects are
      the consequences of weight loss or are due to changes in opioidergic tone is
      debatable.

PMID- 12009348
TI  - A cross-sectional study of the effects of hormon replacement therapy on the
      cardiovascular disease risk profile in healthy postmenopausal women.
AB  - OBJECTIVE: To assess risk factors for cardiovascular disease in healthy
      postmenopausal women who had been uninterruptedly on menopausal hormone
      replacement therapy (HRT) for at least 5 years or who had not received any HRT.
      DESIGN: Cross-sectional study. SETTING: The Royal Free Hospital and The Middlesex
      Hospital. PATIENT(S): A total of 256 healthy postmenopausal women were analyzed:
      73 were taking tibolone, 60 were taking transdermal E(2), 58 were taking
      conjugated equine estrogens (E), and 65 were not taking any menopausal therapy.
      INTERVENTION(S): Cardiovascular disease risk factors measurement. MAIN OUTCOME
      MEASURE(S): Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides,
      lipoprotein(a), insulin, glycated hemoglobin, high sensitivity C-reactive
      protein, fibrinogen, total antioxidants, and endothelin-1. RESULT(S): The
      different types of HRT induced disparate changes in the various markers of
      cardiovascular disease. Significantly higher high sensitivity C-reactive protein
      concentrations were found in women receiving conjugated equine E and tibolone
      than in women who were not taking any therapy. Glycated hemoglobin was
      significantly lower in women receiving transdermal E(2) and tibolone compared to
      women not on HRT. Women on tibolone had significantly higher systolic blood
      pressure. CONCLUSION(S): Because high sensitivity C-reactive protein has recently
      emerged as an important predictor of cardiovascular disease, the higher high
      sensitivity C-reactive protein levels observed in women on conjugated equine
      estrogens and on tibolone have potential important clinical implications.

PMID- 12009349
TI  - Low-dose conjugated equine estrogens elevate circulating neurotransmitters and
      improve the psychological well-being of menopausal women.
AB  - OBJECTIVE: To assess the effect of low-dose conjugated equine estrogens (E) on
      circulating neurotransmitters and the efficacy for the treatment of psychological
      symptoms. DESIGN: Controlled comparative clinical study. SETTING: Endocrine
      Research Unit, Instituto Mexicano del Seguro Social, Mexico. PATIENT(S): Thirty
      postmenopausal women received conjugated equine E. Ten women acted as a
      comparison group. INTERVENTION(S): Conjugated equine E, 0.312 mg/day, for 21 days
      per cycle during six cycles and added chlormadinone acetate, 2 mg/day, for the
      last 5 days of each cycle. Green scale for climateric women and Blatt-Kupperman
      Menopausal Index were used for measuring psychological well-being. MAIN OUTCOME
      MEASURE(S): Serum levels of dopamine (DA), noradrenaline, serotonin, and beta
      endorphin were quantified by specific assays at baseline and at the end of
      treatment. RESULT(S): Low baseline levels of DA, serotonin, and beta-endorphin
      increased significantly (P<.001) from 181.9 +/- 47.8 pg/mL to 202.9 +/- 32.8
      pg/mL (mean +/- SD); from 206.4 +/- 94.2 ng/mL to 279.2 +/- 67.9 ng/mL; from 11.2
      +/- 1.8 pmol/L to 13.8 +/- 2.4 pmol/L, respectively, after conjugated equine E.
      In parallel, augmented baseline noradrenaline levels diminished significantly
      (P<.05) from 30.2 +/- 4.7 ng/mL to 24.0 +/- 4.7 ng/mL. All neurotransmitter
      levels had a significant correlation with 17beta-E(2) concentrations at the end
      of the study. Alleviation of psychological symptoms was observed in all but eight
      treated women. CONCLUSION(S): Low-dose conjugated equine E associated with
      periodic administration of chlormadinone acetate elicited favorable changes in
      neurotransmitters and relieved psychological symptoms.

PMID- 12009350
TI  - Endometrial preparation for frozen-thawed embryo transfer with or without
      pretreatment with gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: To test the efficacy of endometrial preparation with exogenous
      steroids, without pretreatment with gonadotropin-releasing hormone (GnRH)
      agonist, in women with normal ovarian function. DESIGN: Prospective randomized
      study. SETTING: Private outpatient infertility clinic. PATIENT(S): Two hundred
      ninety-six women undergoing frozen-thawed embryo transfer. INTERVENTION(S): In
      group 1 (146 patients), depot GnRH agonist was administered in the luteal phase;
      treatment with 17beta-estradiol transdermal patches at steadily increasing dosage
      from 100 to 300 microg was then given for at least 12 days. In group 2 (150
      patients), endometrial preparation began on day 1 of menstrual cycle. The
      starting dose was 200 microg; this was increased to 300 microg after 7 days. MAIN
      OUTCOME MEASURE(S): Pregnancy, abortion, implantation and cancellation rates.
      RESULT(S): In group 2, six cycles (4%) were cancelled due to evidence of
      ovulation. Groups were similar in the percentage of embryos that survived
      freezing-thawing (77.1% in group 1 and 76.6% in group 2) and in the number of
      embryos transferred per patient (2.1 +/- 0.6 and 2.1 +/- 0.7, respectively).
      Groups 1 and 2 did not differ significantly in rates of pregnancy (19.7% and
      24.1%), abortion (17.8% and 11.7%), and implantation (10.4% and 11.9%).
      CONCLUSION(S): Endometrial preparation for frozen-thawed embryo transfer based
      exclusively on steroid administration appears to be as effective as the more
      conventional protocol involving preliminary desensitization with a GnRH agonist.
      This simplified protocol reduces costs, minimizes pharmacologic treatment, and
      increases patient compliance.

PMID- 12009351
TI  - Urinary follicle-stimulating hormone peak as a biomarker for estimating the day
      of ovulation.
AB  - OBJECTIVE: To evaluate urinary follicle-stimulating hormone (FSH) as a biomarker
      for the day of ovulation. DESIGN: Prospective observational study. SETTING:
      Clinical research center. PATIENT(S): Thirteen women were monitored with
      measurements of serum and urinary hormones and ovarian ultrasonography during 20
      menstrual cycles. Data on urinary hormones and ultrasound evaluations from a
      total of 65 menstrual cycles from 42 women were analyzed. INTERVENTION(S): Blood
      and/or urine samples were collected daily. Daily transvaginal ultrasonography was
      used to detect follicular collapse. MAIN OUTCOME MEASURE(S): LH, FSH, and E(2)
      were measured in serum. FSH, estrone conjugates (E1C), and pregnanediol-3
      glucuronide (PdG) were analyzed in urine. The day of luteal transition (DLT) was
      calculated using two algorithms. RESULT(S): In 20 cycles, the urinary FSH peak
      was closer to the day of follicular collapse (-0.85 days) than was the peak day
      of serum E(2) and the day of luteal transition, as calculated by one algorithm.
      The FSH peak was not closer to the day of follicular collapse than the peak
      values of urinary LH, serum FSH, or the day of luteal transition as calculated by
      a second algorithm. The most consistent correspondence between a hormone peak and
      ovulation was for serum E(2), serum FSH, serum LH, and urinary FSH. In 65 cycles
      for which urinary hormone data and ultrasound evaluations were available, the
      urinary FSH peak occurred within 1 day of follicular collapse in 97% of cycles.
      CONCLUSION(S): Urinary FSH is a useful biomarker for estimating the day of
      ovulation in population-based studies.

PMID- 12009352
TI  - Effect of repeated assisted reproductive technology cycles on ovarian response.
AB  - OBJECTIVE: To assess the effect of repeated assisted reproductive technology
      (ART) cycles on the ovarian response in patients treated with human menopausal
      gonadotropins and GnRH agonists. DESIGN: Retrospective analysis. SETTING:
      Tertiary referral center. PATIENT(S): Three thousand two hundred forty-nine
      patients who had completed at least two in vitro fertilization (IVF) or
      intracytoplasmic sperm injection (ICSI) cycles (minimum two, maximum six cycles
      per patient). INTERVENTION(S): Nine thousand three hundred seventy-nine repeated
      IVF/ICSI cycles. MAIN OUTCOME MEASURE(S): Mean number of cumulus oocyte complexes
      (COC) retrieved per cycle, mean number of ampules used per attempt. RESULT(S):
      Repeated ART cycles did not exert a significant effect on the mean number of COC
      retrieved per attempt in contrast to maternal age, which was inversely related to
      the mean number of COC retrieved in all cycles performed. Across repeated ART
      attempts, an increase in the mean number of ampules used per cycle was observed.
      This was due to an effect of maternal age, which increased in line with the mean
      number of ampules used per cycle, as well as to an age-independent effect of
      repeated cycles. CONCLUSION(S): An age-independent deterioration of the ovarian
      response appears to occur across repeated ART cycles.

PMID- 12009353
TI  - Prospective evaluation of blastocyst stage transfer vs. zygote intrafallopian
      tube transfer in patients with repeated implantation failure.
AB  - OBJECTIVE: To compare extended culture with blastocyst stage transfer and zygote
      intrafallopian transfer (ZIFT) in the management of IVF patients with repeated
      implantation failure. DESIGN: Prospective, nonrandomized study. SETTING: An IVF
      unit at a university hospital. PATIENT(S): Sixty-four infertile patients with
      more than three previous failed IVF-ET attempts. INTERVENTION(S): Patients were
      allocated to undergo either blastocyst stage transfer (Group 1; n = 32) or ZIFT
      (Group 2; n = 32). MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, and
      live birth rates. RESULT(S): Patient characteristics and response to stimulation
      were comparable for both groups. Totals of 84.3% and 97% of the patients
      underwent blastocyst transfer and ZIFT, respectively. Significantly more embryos
      were transferred through ZIFT (5.5+/-0.8) as compared with blastocyst transfer
      (2.3+/-1.4), and there were significantly more cycles with embryo
      cryopreservation in the ZIFT group as compared to the blastocyst transfer group
      (15/32 vs. 4/32, respectively). Implantation rate (13.6% vs. 1.4%), clinical
      pregnancy rate (40.6% vs. 3.1%), and live birth rates (38.7% vs. 0%) were all
      significantly higher in the ZIFT group as compared to the blastocyst transfer
      group, respectively. CONCLUSION(S): Zygote intrafallopian transfer is a powerful
      clinical tool in the management of patients with RIF. In contrast, blastocyst
      stage transfer fails to improve the outcome in this poor-prognosis group. The
      pathophysiology of RIF should be the subject of intense investigation to allow
      the introduction of appropriate therapeutic measures earlier in the course of
      treatment.

PMID- 12009354
TI  - A low number of retrieved oocytes at in vitro fertilization treatment is
      predictive of early menopause.
AB  - OBJECTIVE: To investigate whether women with a low number of retrieved oocytes at
      the first in vitro fertilization (IVF) attempt have an increased risk of early
      menopause. DESIGN: Nested case-control study. SETTING: Twelve IVF clinics in the
      Netherlands. PATIENT(S): Women participating in a nationwide Dutch cohort study
      (OMEGA) of ovarian stimulation for IVF and subsequent gynecologic diseases (n =
      26,428). Each patient who experienced natural menopause at or before 46 years (n
      = 38) was individually matched to five controls (n = 190) who had not yet entered
      menopause at the age the patient became postmenopausal. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Relative risk of reaching natural menopause at an early
      age (</=46 years), according to the number of retrieved oocytes at the first IVF
      attempt. RESULT(S): Women with a poor response (zero to three oocytes) had a
      relative risk of 11.6 (95% confidence interval: 3.9-34.7) of having an early
      menopause as compared with women who have a normal response (> three oocytes).
      Women who were stimulated with gonadotropins during IVF treatment but did not
      undergo an IVF puncture because of an anticipated poor response (canceled IVF
      cycle) had a relative risk of 8.3 (95% confidence interval: 2.9-23.9).
      CONCLUSION: These results suggest that women with a low number of retrieved
      oocytes at the first IVF treatment are more likely to become postmenopausal at an
      early age than women with a higher number of retrieved oocytes. Our study is the
      first longitudinal study to provide strong evidence for the quantitative aspect
      of the ovarian concept of reproductive aging.

PMID- 12009355
TI  - Effect of paracentesis of ascitic fluids on urinary output and blood indices in
      patients with severe ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To determine the isolated effect of abdominal paracentesis of ascitic
      fluid in women with severe OHSS on urine production and blood indices. DESIGN:
      Retrospective interventional study. SETTING: Gynecology department at the Lis
      Maternity Hospital, affiliated to Tel Aviv University. PATIENT(S): Thirty women
      with severe OHSS. INTERVENTION(S): Abdominal paracentesis according to clinical
      indications. MAIN OUTCOME MEASURE(S): Urinary output, blood urea nitrogen, as
      well as a complete blood count were measured before and following the procedure.
      RESULT(S): Urinary output increased from 1890 +/- 128 mL per 24 hours on the day
      before paracentesis to 2,660 +/- 226 mL per 24 hours after the procedure. Blood
      urea nitrogen values were 8.9 +/- 0.56 mg/dL and 7.8 +/- 0.53 mg/dL on the days
      before and after paracentesis, respectively. White blood cell count decreased
      from 15.4 +/- 1.1 (x 10(3) cells/mm(3)) on the days before the paracentesis to
      13.3 +/- 0.9 (x 10(3) cells/mm(3)) after the procedure. Hematocrit was reduced
      significantly from 35.2 +/- 1.0% before the paracentesis to 33.4 +/- 0.8% after
      paracentesis. CONCLUSION(S): Paracentesis of ascitic fluids in women with severe
      OHSS has an isolated effect in improving renal function, as is evident by the
      increased urinary output and reduced blood urea nitrogen.

PMID- 12009356
TI  - Spontaneous and stimulated secretion of monocyte chemotactic protein-1 and
      macrophage migration inhibitory factor by peritoneal macrophages in women with
      and without endometriosis.
AB  - OBJECTIVE: To assess spontaneous and stimulated secretion of monocyte chemotactic
      protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF) by peritoneal
      macrophages in women with and without endometriosis. DESIGN: Macrophages were
      isolated from the peritoneal fluid and cultured for different periods of time (6,
      20, and 44 hours) without any stimulation to determine spontaneous secretion of
      MCP-1 and MIF. Macrophages were also exposed to 1 microg/mL lipopolysaccharide
      for 6 hours to evaluate the stimulated secretion of these cytokines. SETTING:
      Gynecology clinic and human reproduction research laboratory. PATIENT(S): Twelve
      fertile women and 11 women with endometriosis. INTERVENTION(S): Peritoneal fluid
      obtained at laparoscopy. MAIN OUTCOME MEASURE(S): Monocyte chemotactic protein-1
      and MIF concentrations in the culture medium using ELISA. RESULT(S): Peritoneal
      macrophages of women with endometriosis demonstrated an increased capacity to
      secrete MCP-1 either spontaneously or after stimulation with lipopolysaccharide.
      They also showed a marked tendency for an increased secretion of MIF, but no
      statistically significant difference was found. CONCLUSION(S): Monocyte
      chemotactic protein-1 and MIF production by peritoneal macrophages may contribute
      to paracrine and autocrine activation and to macrophage accumulation in the
      peritoneal cavity of women with endometriosis. These mechanisms may exacerbate
      peritoneal inflammation and favor the growth of endometrial implants.

PMID- 12009357
TI  - Effect of mifepristone on estrogen and progesterone receptors in human
      endometrial and endometriotic cells in vitro.
AB  - OBJECTIVE: To investigate the expressions of estrogen (E) receptor and
      progesterone (P) receptor in human eutopic and ectopic endometrium and the effect
      of mifepristone (RU486) on them. DESIGN: Prospective study. SETTING: University
      hospital. PATIENT(S): Twenty-two patients with ovarian endometriosis and 13
      patients with uterine leiomyoma were recruited. INTERVENTION(S): Samples of
      ovarian endometrioma cyst tissue and endometrium were obtained from the 22
      patients. A sample of endometrium was obtained from the 13 patients. MAIN OUTCOME
      MEASURE(S): Expressions of E and P receptors were determined using
      immunocytochemical method. RESULT(S): P receptor expression in endometrial
      epithelial cells with endometriosis was significantly higher than that without
      endometriosis in the early secretory phase. Estrogen receptor and epithelial P
      receptor expressions in endometriotic cells were significantly lower than those
      of endometrial cells during the proliferative phase, similar with the latter
      during the early secretory phase and significantly higher during the late
      secretory phase. RU486 down-regulated the expressions of E and P receptors in
      both the eutopic and the ectopic endometrial cells, and in some cases this down
      regulating effect was more apparent when the concentration of RU486 was higher.
      CONCLUSION(S): Different steroid receptor expressions indicate different hormonal
      regulation between endometriotic and endometrial cells. The down-regulating
      effect on E and P receptors may be one of the therapeutic mechanisms of RU486 on
      endometriosis.

PMID- 12009358
TI  - Decreased progesterone receptor expression in the intermediate trophoblastic
      cells of spontaneous abortions.
AB  - OBJECTIVE: To determine whether there are differences in the expression of
      progesterone receptor (PR) in intermediate trophoblastic cells of pregnancies
      ending in either spontaneous abortion (SAB) or elective abortion. DESIGN:
      Immunohistochemical identification of PR in intermediate trophoblastic cells.
      SETTING: Academic medical center. PATIENT(S): Subjects were 86 patients who
      either underwent first trimester SAB or elective abortion. INTERVENTION(S): All
      SAB and elective abortion specimens were serially sectioned and
      immunohistochemically stained for PR and for melanoma cell adhesion molecule.
      Melanoma cell adhesion molecule immunohistochemical staining was used as a
      sensitive and specific marker to identify intermediate trophoblastic cells on the
      adjacent tissue section. MAIN OUTCOME MEASURE(S): The PR staining of intermediate
      trophoblastic cells by semiquantitative immunostaining score. RESULT(S): The PR
      expression in intermediate trophoblastic cells was significantly greater in
      elective abortion specimens than in SAB specimens. When controlling for estimated
      gestational age, the difference in PR expression was even greater. CONCLUSION(S):
      The quantity of PR in intermediate trophoblastic cells is significantly less in
      SAB when compared to elective abortion pregnancies. Although it is unknown
      whether this is a primary or secondary event, this information may be an
      important finding in attempting to characterize both the molecular etiology of
      implantation and the molecular pathophysiology of SAB.

PMID- 12009359
TI  - The apoptotic profile of human cumulus cells changes with patient age and after
      exposure to sperm but not in relation to oocyte maturity.
AB  - OBJECTIVE: To determine the expression of apoptosis-associated molecules on
      cumulus cells removed from individual oocytes of different maturity, inseminated
      oocytes and to investigate the possibility of an age-dependent expression.
      DESIGN: Analysis of apoptosis in cumulus cells isolated from oocytes of different
      stages of maturity. SETTING: Assisted reproductive technology program of the
      Birmingham Women's Hospital, Birmingham, UK. PATIENT(S): Patients undergoing
      intracytoplasmic sperm injection or IVF cycles. MAIN OUTCOME MEASURE(S):
      Percentage of positive cumulus cells when assessed for nuclear DNA damage using
      the terminal deoxyuridine nucleotide end-labeling assay or stained with
      antibodies [Fas, Fas ligand, the antiapoptotic protein Bcl-xl, and the RNA
      binding protein (TIAR)]. RESULT(S): Cumulus cells collected from mature oocytes
      showed no significant difference in the percentage of apoptotic markers compared
      to those recovered from immature oocytes, whereas those from patients >/=38 years
      differed significantly. When cumulus cells were exposed to sperm the levels of
      apoptotic markers altered significantly from those not exposed to sperm.
      CONCLUSION(S): The results show that the cumulus cells of human oocytes are
      equipped with a mechanism to undergo apoptosis and that patient age and the
      exposure of cumulus cells to sperm can alter their profiles of apoptotic markers.

PMID- 12009360
TI  - Multiple rearrangements of mitochondrial DNA in unfertilized human oocytes.
AB  - OBJECTIVE: To determine the rearrangement of mitochondrial DNA (mtDNA) in
      unfertilized human oocytes and compromised embryos to evaluate the fertilization
      capacity of oocytes. DESIGN: Prospective laboratory research. SETTING: IVF
      laboratory in a university hospital. PATIENT(S): One hundred twenty-four
      unfertilized oocytes, 98 arrested embryos, and 45 tripronucleate (3PN) embryos
      from 65 female patients undergoing in vitro fertilization (IVF). INTERVENTION(S):
      Unfertilized oocytes and poor quality embryos were collected 48 hours after IVF.
      MAIN OUTCOME MEASURE(S): Comparison of the frequency of mtDNA deletions and
      fertilization rates of oocytes. RESULT(S): Multiple deletions of mtDNA were found
      in unfertilized oocytes and arrested embryos obtained from IVF patients. A 4977
      bp deletion was the most frequent deletion in human oocytes and embryos. About
      66.1% of the unfertilized oocytes, 34.8% of the arrested or fragmented embryos,
      and 21.1% of the 3PN embryos harbored the 4977-bp deletion of mtDNA. There was a
      significant increase in the proportion of deleted mtDNA in unfertilized oocytes.
      CONCLUSION(S): Accumulation of mtDNA deletions may contribute to mitochondrial
      dysfunction and impaired ATP production. We conclude that the accumulation of
      rearranged mtDNA may interfere with fertilization of human oocytes and further
      embryonic development.

PMID- 12009361
TI  - Effects of the new generation selective estrogen receptor modulator EM-652 and
      oral administration of estradiol valerate on circulating, brain, and adrenal beta
      endorphin and allopregnanolone levels in intact fertile and ovariectomized rats.
AB  - OBJECTIVE: To investigate the effects of oral estradiol valerate (EV); EM-652, a
      new-generation selective estrogen receptor modulator; and both agents on central
      and peripheral beta-endorphin (beta-EP) and allopregnanolone levels in fertile
      and ovariectomized rats. DESIGN: Prospective study. SETTING: Animal laboratory in
      an academic research environment. ANIMALS: Thirteen groups of eight Wistar female
      rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1,
      or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily)
      for 14 days. INTERVENTION(S): beta-Endorphin levels content in the hypothalamus,
      hippocampus, anterior and neurointermediate pituitary, and plasma were measured.
      Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary,
      adrenal glands, and serum were measured. MAIN OUTCOME MEASURE(S): beta-Endorphin
      and allopregnanolone levels. RESULT(S): In ovariectomized rats, administration of
      EV or EM-652 reverses changes in beta-EP and allopregnanolone levels induced by
      ovariectomy. Administration of EM-652 plus EV prevents the increase in beta-EP
      and allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and
      pituitary but not in the adrenal glands and serum. CONCLUSIONS: In ovariectomized
      rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the
      presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or
      slight antiestrogenic effects.

PMID- 12009362
TI  - Use of serum-soluble intercellular adhesion molecule-1 as a new marker of
      endometriosis.
AB  - OBJECTIVE: To investigate the hypothesis that soluble intercellular adhesions
      molecule-1 (sICAM-1) may be used as a new serum marker of endometriosis. DESIGN:
      Prospective cohort study. SETTING: An academic department specializing in
      gynecologic laparoscopy. PATIENT(S): Consecutive series of 120 women of
      reproductive age who underwent laparoscopy for benign gynecologic conditions.
      INTERVENTION(S): Data were collected on baseline clinical characteristics, and
      surgical and histologic diagnosis. MAIN OUTCOME MEASURE(S): Serum concentration
      of both CA125 and sICAM-1. RESULT(S): Endometriosis was documented in 71 women
      (stage I to II in 24 cases and stage III to IV in 47 cases). Serum levels of
      sICAM-1 were only slightly but not significantly increased in women with
      endometriosis compared with women without the disease. However, serum
      concentration of sICAM-1 in the 21 women who were found to have deep peritoneal
      endometriosis was significantly enhanced when compared with both women without
      the disease and those with other forms of endometriosis. The sensitivity and
      specificity of sICAM-1 in detecting deep peritoneal endometriosis were 0.19 and
      0.97, respectively; whereas those of CA125 were 0.14 and 0.92, respectively. When
      both parameters were used concomitantly, the sensitivity and specificity were
      0.28 and 0.92, respectively. CONCLUSION(S): Although the present study tends to
      support a role of sICAM-1 in the development of endometriosis, serum
      concentrations of this molecule do not seem to be an effective indicator for the
      diagnosis of either the early or advanced stage of endometriosis. However, an
      integrated clinical and laboratory approach using both CA125 and sICAM-1 may be
      helpful in specifically identifying women with deep peritoneal endometriosis.

PMID- 12009363
TI  - Cytokine production in natural killer cells and lymphocytes in pregnant women
      compared with women in the follicular phase of the ovarian cycle.
AB  - OBJECTIVE: To test whether peripheral natural killer (NK) cells, helper T cells,
      and cytotoxic lymphocytes of pregnant women shift from a type 1 cytokine
      production toward a type 2 cytokine production as compared with these cells in
      women in the follicular phase. DESIGN: Prospective study. SETTING: Outpatient
      clinic. PATIENT(S): Healthy nullipara at 30 weeks' amenorrhea and healthy
      nonpregnant women in their follicular phase. INTERVENTION(S): Samples of whole
      blood were stimulated with phorbol myristate acetate (PMA; Sigma Chemical Co.,
      St. Louis, MO) and Ca-ionophore in the presence of monensin (Sigma). Lymphocytes
      were stained with alpha-CD3, alpha-CD8, and alpha-interferon gamma (IFN-gamma)
      alpha-interleukin 2 (IL-2), IL-4, or IL-10. Analysis was performed by flow
      cytometry. Statistical evaluation was done with the Mann-Whitney U test. MAIN
      OUTCOME MEASURE(S): Percentage NK cells, helper lymphocytes, and cytotoxic
      lymphocytes that were producing IFN-gamma, IL-2, IL-4, or IL-10. RESULT(S): There
      is a statistically significant decrease in the percentage of NK cells, and helper
      and cytotoxic lymphocytes that produced IFN-gamma in pregnant women when compared
      with women in the follicular phase. There is also a statistically significant
      decrease in the percentage of helper lymphocytes producing IL-2 in pregnant women
      compared with nonpregnant women. CONCLUSION(S): We found a decrease in type 1
      cytokine production with no change in type 2 cytokine production after in vitro
      stimulation of "pregnant" NK cells and lymphocytes as compared with "nonpregnant"
      NK cells and lymphocytes. We suggest that NK cell and lymphocyte response are
      shifted away from a type 1 immune response during pregnancy.

PMID- 12009364
TI  - Effect of estrogen and 1alpha,25(OH)2- vitamin D3 on the activity and growth of
      human primary osteoblast-like cells in vitro.
AB  - OBJECTIVE: To evaluate effects of 17beta-E(2) and 1alpha,25(OH)(2)-vitamin D(3)
      on human osteoblast-like (hOB) cells. DESIGN: Controlled, experimental study.
      SETTING: University hospital. PATIENT(S): hOB cell cultures were prepared from
      the upper femur of postmenopausal patients undergoing bipolar endoprosthesis
      arthroplasty for a fractured femoral neck. INTERVENTION(S): hOB cells were
      subcultured with either 17beta-E(2) or 1alpha,25(OH)(2)-vitamin D(3), or both.
      MAIN OUTCOME MEASURE(S): Cell proliferation and activity of alkaline phosphatase,
      osteocalcin, and interleukin-6. RESULT(S): 17beta-E(2) significantly reduced
      interleukin-6 and osteocalcin to 34% and 60% of control value but induced
      alkaline phosphatase and cell proliferation to 183% and 150% of control value.
      1alpha,25(OH)(2)-vitamin D(3) significantly decreased cell proliferation to 88%
      of that of control group, but 1alpha,25(OH)(2)-vitamin D(3) plus 17beta-E(2)
      showed no difference from the control group. Alkaline phosphatase and osteocalcin
      were significantly increased by 1alpha,25(OH)(2)-vitamin D(3) alone or combined
      with 17beta-E(2), to 169% and 198% and to 144% and 144% of control value,
      respectively. 1alpha,25(OH)(2)-vitamin D(3), with or without 17beta-E(2),
      decreased interleukin-6 levels to 27% and 38% of control group, respectively.
      CONCLUSION(S): 17beta-E(2) and 1alpha,25(OH)(2)-vitamin D(3) have effects on
      osteoblasts. The prevention of osteoporosis by estrogen may be related not only
      to direct effects on osteoblastic activity and proliferation but also to indirect
      effects on osteoclasts by the decrease of interleukin-6 secretion.

PMID- 12009365
TI  - Chymase inhibitors may prevent postoperative adhesion formation.
AB  - OBJECTIVE: To clarify the role of chymase produced from mast cells in adhesion
      formation, we measured chymase activity level and investigated the preventive
      effect of a chymase inhibitor, Suc-Val-Pro-Phe(p)(OPh)(2), on the postoperative
      adhesion formation. DESIGN: Prospective randomized study using a surgical model
      for adhesion formation. SETTING: Clean hamsters in an academic research
      environment. ANIMAL(S): Sixty-seven female Syrian hamsters. INTERVENTION(S):
      Hamsters were given a lesion, produced by uterus scraping, and the chymase
      inhibitor (10 microM) or placebo was injected into the abdomen. Chymase
      activities in uteri were measured 3 days after the operation, and the scores of
      adhesion formations were assessed at 2 weeks. MAIN OUTCOME MEASURE(S):
      Measurement of chymase activity and scoring of adhesion formation were performed.
      RESULT(S): A significant increase of chymase activity in the injured uterus
      reduced by treatment with the chymase inhibitor. The scores of adhesion
      formations in the chymase inhibitor-treated group were significantly decreased in
      comparison with those in the placebo-treated group. CONCLUSION(S): Chymase
      contained in mast cells plays an important role in adhesion formation, and a
      chymase inhibitor may be a useful drug for prevention of adhesion formation.

PMID- 12009366
TI  - The learning curve of selective salpingography and tubal catheterization.
AB  - OBJECTIVE: To determine the effect of increasing experience in fluoroscopically
      guided selective salpingography and tubal catheterization on radiation doses and
      screening times, thus establishing a learning curve for the procedure. DESIGN:
      Retrospective case note analysis. SETTING: IVF center of an academic teaching
      hospital. PATIENTS: Three hundred sixty-six patients with infertility seen over
      3.5 years. INTERVENTION(S): Fluoroscopically guided selective salpingography and
      tubal catheterization. MAIN OUTCOME MEASURE(S): Reductions in radiation doses and
      screening times for different categories of selective salpingography and tubal
      catheterization, expressed as percentage reductions during the study period and
      reductions per 10 procedures. RESULT(S): During the study period, The median dose
      of radiation decreased by 62.6%-71.9%, and the median screening time declined by
      61.5%-78.5%. Reductions per 10 procedures were 2.5%-4.2% and 2.7%-5%,
      respectively. CONCLUSION(S): Significant reductions in radiation doses and
      screening times start early in a clinical team's practice of selective
      salpingography and tubal catheterization and continue even as trainees are added
      to the pool of operators.

PMID- 12009367
TI  - Ovarian bivalving after detorsion.
AB  - OBJECTIVE: To assess the efficacy of a new technique, ovarian bivalving, on
      facilitating adnexal recovery after adnexal torsion. DESIGN: Retrospective case
      series. SETTING: Academic medical center. PATIENT(S): Five patients undergoing
      conservative surgical management of adnexal torsion at the Children's Hospital,
      Boston, Massachusetts, from May 1999 to April 2000. INTERVENTION(S): Performance
      of ovarian bivalving after untwisting of adnexal torsion. MAIN OUTCOME
      MEASURE(S): Sonographic appearance of adnexa after ovarian bivalving, and
      postoperative complications. RESULT(S): After surgical treatment, four of five
      patients undergoing untwisting of adnexa and ovarian bivalving had
      sonographically confirmed normal follicular function; in three of five cases, it
      was confirmed with Doppler arterial flow. There were no postoperative
      complications. CONCLUSION(S): After the untwisting of ischemic adnexa, ovarian
      bivalving is an effective technique to decrease ovarian intracapsular pressure,
      increase arterial perfusion, and facilitate adnexal reperfusion and recovery.

PMID- 12009368
TI  - A simple DNA disc chip in a microarray design based on modified comparative
      genomic hybridization for sperm DNA analysis.
AB  - OBJECTIVE: A DNA disc chip assay, based on comparative genomic hybridization, was
      designed to measure changes in sperm DNA intensities. The objective was to
      analyze the DNA integrity of hyperactive sperm cells after mild heat treatment.
      DESIGN: The assay based on a multiple cell comet assay was used to analyze
      changes in genomic DNA. Washed sperm DNA were tested on the assay and images
      stored in a microarray design. SETTING: Clinical and academic research
      environment. PATIENT(S): Frozen-thawed washed sperm from different donors (n =
      7). INTERVENTION(S): Discarded sperm leftover from trial washes carried out at 37
      degrees and 40 degrees C were frozen and processed for the DNA disc chip assay.
      MAIN OUTCOME MEASURE(S): Fluorescent intensities of DNA disc chips and sperm
      variables. RESULT(S): Heat treatment resulted in more than eightfold increase in
      sperm hyperactive motility with little degradation in DNA integrity. Sperm with
      low hyperactivation was associated with alterations in DNA after heat treatment.
      CONCLUSION(S): The DNA disc chip assay was simple, inexpensive, and permitted
      assisted reproduction technologies laboratories to use comparative genomic
      hybridization for cytogenotoxicity testing. However, the assay required manual
      processing, a fluorescent microscope, and computer. The data showed an
      association between sperm hyperactivation and DNA integrity suggesting that the
      hyperactivation marker may be used for selecting quality sperm for
      intracytoplasmic sperm injection. More studies are needed to examine temperature
      effects on ejaculated human sperm.

PMID- 12009369
TI  - Transcervical needle biopsy of uterine myoma-like tumors using an automatic
      biopsy gun.
AB  - OBJECTIVE: To describe a practical procedure of transcervical needle biopsy of
      uterine myoma-like tumors using an automatic biopsy gun and its potential risks.
      DESIGN: Description of new biopsy procedure. SETTING: University teaching
      hospital. PATIENT(S): Three hundred twelve patients who had been recommended for
      surgery for uterine myoma-like tumors by the hospital's outside doctors.
      INTERVENTION(S): Transcervical needle biopsy of uterine myoma-like tumors. MAIN
      OUTCOME MEASURE(S): Successful sampling rate, duration of procedure, estimated
      blood loss, patient discomfort, and complications. RESULT(S): Of the 312 patients
      who underwent transcervical needle biopsy, specimens were obtained from 311
      (99.7%). The mean (+/- SD) duration of procedure was 6.3 +/- 5.2 minutes. The
      mean estimated blood loss was 10.4 +/- 10.9 g. There were two cases (0.6%) in
      which the blood loss during the procedure was in excess of 50 g, but bleeding can
      be conservatively controlled in such cases with an intrauterine tamponade using
      gauze or a balloon catheter. The level of patient pain and discomfort during the
      needle biopsy was significantly lower than that during endometrial curettage. No
      major complications requiring surgery occurred. CONCLUSION(S): Transcervical
      needle biopsies of uterine myoma-like tumors using an automatic biopsy gun are
      practical, simple, and safe. This new procedure can be of routine clinical use.

PMID- 12009370
TI  - Randomized trial of one versus two transcervical insertions of quinacrine pellets
      for sterilization.
AB  - OBJECTIVE: To determine the relative effectiveness of single vs. two
      transcervical monthly insertions of 252 mg of quinacrine for female
      sterilization. DESIGN: Controlled clinical study. SETTING: Family planning
      clinics of 6 academic centers. PATIENT(S): Sexually active reproductive-age women
      requesting sterilization. INTERVENTION(S): At each of six centers 70 and 30 women
      were randomly assigned to receive either one or two, respectively, monthly
      transcervical insertions to the fundus of 252 mg of quinacrine and 75 mg of
      diclofenac as pellets and they were followed for 1 year. MAIN OUTCOME MEASURE(S):
      Complications, side effects, and pregnancy failures. RESULT(S): There were no
      serious complications and side effects were transient and easily treated. There
      were 31 (7.4%) pregnancy failures in the single insertions group and 2 (1.1%) in
      the two insertions group, but with marked center variation. CONCLUSION(S):
      Quinacrine sterilization using two monthly insertions of 252 mg of quinacrine
      appears safe and reasonably effective.

PMID- 12009371
TI  - Diagnosis of simple endometrial hyperplasia in a woman with polycystic ovary
      syndrome with use of hysterosalpingography.

PMID- 12009372
TI  - Management of missed abortion in a patient with congenital cervical atresia.
AB  - OBJECTIVE: To describe a patient with congenital cervical atresia who became
      pregnant through IVF and thawed transmyometrial ET and then experienced a missed
      abortion. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A
      patient with congenital cervical atresia who underwent reconstructive surgery at
      23 years of age and underwent IVF twice at 28 and 30 years of age.
      INTERVENTION(S): Abortion management. MAIN OUTCOME MEASURE(S): Medical follow-up
      of IVF-ET, resultant pregnancy, and abortion. RESULT(S): After the second cycle
      of IVF with frozen-thawed transmyometrial ET, the patient became pregnant but
      then experienced a missed abortion. Serum beta-hCG levels decreased, the two
      gestational sacs disappeared, and genital bleeding without signs of infection
      occurred 14 weeks after diagnosis of the abortion. The abortion was managed
      conservatively. CONCLUSION(S): When assisted reproductive techniques are used in
      patients with congenital cervical atresia, the risks (including those relating to
      the management of an abortion) should be explained in detail to the couple and
      sufficient informed consent should be obtained before starting IVF-ET procedures.

PMID- 12009373
TI  - Birth of a healthy baby after transfer of embryos that were cryopreserved for 8.9
      years.
AB  - OBJECTIVE: To report successful pregnancy from embryos that had been
      cryopreserved for 8.9 years. DESIGN: Case report. SETTING: Fertility clinic of
      the University of Buenos Aires School of Medicine. PATIENT(S): A 43-year-old
      woman with ovarian failure and a 45-year-old man with nonobstructive azoospermia
      underwent embryo donation.I NTERVENTION(S): Five embryos that had been
      cryopreserved and stored since 1989 were thawed in 1998 and donated to an
      infertile couple. Endometrial preparation was performed with 17beta-estradiol and
      progesterone. The four embryos with better morphologic characteristics were
      transferred into the uterus. MAIN OUTCOME MEASURE(S): Post-thaw embryo survival,
      pregnancy, and birth. RESULT(S): Embryo survival was satisfactory as assessed by
      morphology. Pregnancy was confirmed by ultrasonography. A healthy baby weighing
      2120 g was delivered by cesarean section at 36 weeks. CONCLUSION(S): Human 8-cell
      embryos may be viable after extended storage and can result in successful
      pregnancy.

PMID- 12009374
TI  - Successful pregnancy and delivery after testicular sperm extraction despite an
      undetectable concentration of serum inhibin B in a patient with nonobstructive
      azoospermia.
AB  - OBJECTIVE: To describe a successful pregnancy and delivery after testicular sperm
      extraction (TESE) despite an undetectable concentration of serum inhibin B in a
      man with nonobstructive azoospermia. DESIGN: Case report. SETTING: Obstetrics and
      gynecology and reproductive biology departments. PATIENT(S): A 31-year-old woman
      and a 32-year-old man with nonobstructive azoospermia and an undetectable inhibin
      B serum level. INTERVENTION(S): TESE, testicular spermatozoa cryopreservation,
      intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Pregnancy and
      delivery. RESULT(S): Successful pregnancy and delivery of a normal healthy child
      following a third ICSI cycle with frozen-thawed spermatozoa extracted from the
      testis. CONCLUSION(S): This case report shows that there is no minimal level of
      inhibin B below which TESE is always unsuccessful. The delivery of a normal
      healthy baby is strong evidence to perform TESE in these circumstances.

PMID- 12009375
TI  - Mutation screening for the 5alpha-reductase type 2 gene in Japanese men with
      idiopathic azoospermia.

PMID- 12009376
TI  - Prediction of the effects of gonadotropin-releasing hormone agonist therapy in
      uterine leiomyoma by T1 contrast-enhanced magnetic resonance imaging sequences.

PMID- 12009377
TI  - Cell allocation and cell death in blastocysts from nonhuman primates generated
      during in vitro fertilization and intracytoplasmic sperm injection.

PMID- 12009378
TI  - Surgically induced menopause and blood flow in cerebral arteries.

PMID- 12009379
TI  - "Advance directives" for disposition of gametes?

PMID- 12009381
TI  - A role for melatonin in PCOS?

PMID- 12009384
TI  - Csapo redux, but more veils remain.

PMID- 12009385
TI  - Prostaglandins and prostanoid receptors in human pregnancy and parturition.
AB  - Preterm labor occurs in up to 10% of all births but is associated with 85% of
      perinatal deaths in otherwise normal babies. Elucidation of the mechanisms
      involved in normal labor is an important prerequisite for the development of
      effective therapeutic strategies to prevent and treat preterm labor.
      Prostaglandins are important in human parturition. They have been used
      extensively for induction of labor. Prevention of their formation with
      prostaglandin synthase inhibitors can delay delivery in preterm labor.
      Nevertheless, the functional activity of prostaglandins in gestational tissues is
      complex. There are numerous classes of prostaglandins that act on many different
      prostanoid receptors. Receptor subtypes, even within the same class, are coupled
      to various second messengers and may thus be stimulatory or inhibitory. Alternate
      splicing leads to additional diversity. Within this complex background, the
      tissue-, gestation-, and labor-associated changes in prostaglandins and their
      receptors are reviewed.

PMID- 12009386
TI  - Progesterone receptor localization and isoforms in myometrium, decidua, and fetal
      membranes from rhesus macaques: evidence for functional progesterone withdrawal
      at parturition.
AB  - OBJECTIVE: It is not known whether withdrawal of progesterone (P) action is a
      prerequisite for parturition in women or in nonhuman primates because
      concentrations of circulating progesterone or progesterone receptors (PR) in
      myometrium and decidua do not decrease before delivery. To examine this
      potentially important regulatory mechanism, we determined PR isoforms, PR
      localization, and mRNA in myometrium, decidua, and fetal membranes from rhesus
      monkeys during pregnancy and in spontaneous labor at term. METHODS: Gestational
      tissues were obtained midpregnancy (day 80-100), late pregnancy (day 130-145),
      and during spontaneous labor at term (day 161-167). Samples of rhesus monkey
      myometrium, decidua, chorion-decidua, and amnion were collected and analyzed for
      total nuclear and cytosolic PR by competitive binding assay. Progesterone
      receptor isoforms were identified and quantified by Western blot analysis, and PR
      mRNA was determined by a specific ribonuclease protection assay. Nuclear PR was
      localized by immunohistochemistry with monoclonal anti-PR (JZB39) after microwave
      stabilization. RESULTS: Myometrium and decidua showed no change in total PR
      during pregnancy and labor. Nuclear PR was not detected in fetal membranes by
      binding assay but was localized in amnion epithelial and mesenchymal cells and in
      chorion laeve cytotrophoblasts by immunohistochemistry. Staining for PR was
      substantially less by serial antibody dilution in fetal membranes than in
      decidua. Message for PR was confirmed in all tissues analyzed. A significant (P
      <.05) shift in the ratio of PR isoforms (from PR-B dominance at midpregnancy to
      PR-A dominance in labor) was observed in myometrium but not in decidua. Both PR-A
      and PR-B isoforms and PR nuclear staining were nearly undetectable in amnion
      obtained during labor. CONCLUSION: A shift to PR-A dominance in myometrium at
      term together with a loss of PR in fetal membranes provides evidence for a
      functional progesterone withdrawal mechanism, which may facilitate the initiation
      of parturition in primates.

PMID- 12009387
TI  - Matrix metalloproteinases-2 and -9 and their endogenous tissue inhibitors in
      tissue remodeling after sealing of the fetal membranes in a sheep model of
      fetoscopic surgery.
AB  - OBJECTIVES: We studied collagen plugging of the fetoscopic access site in an in
      vivo fetal lamb model for fetoscopic surgery and possible role for matrix
      metalloproteinase (MMP)-2 and -9 and tissue inhibitors (TIMPs). METHODS: Eight
      ewes had fetoscopic balloon occlusion of the trachea as an experimental treatment
      for congenital diaphragmatic hernia between days 88 and 99 of gestation (term 145
      days) with sampling of amniotic, allantoic, and tracheal fluid. Nonoperated
      cotwins were used as controls. The fetoscopy port was closed using a collagen
      plug. Ten days (range 9-12) later, fluids were sampled and plug sites collected
      for histologic analysis. Activity of MMP-2 (72 kDa, gelatinase A) and MMP-9 (92
      kDa, gelatinase B) was determined in the fluids by zymography and secretion of
      TIMPs (27-30 kDa; TIMP-1, glycosylated TIMP-3 and TIMP-4, 24 kDa; unglycosylated
      TIMP-3, 21 kDa; TIMP-2) by reverse zymography and quantified by densitometric
      analysis. RESULTS: No pregnancy was complicated by amniorhexis or preterm labor.
      At cesarean, normal volumes of amniotic and allantoic fluid were present in all
      cases. Histology of the plug sites revealed good integration of the collagen plug
      without complete restoration of membrane integrity. MMP-2, MMP-9, and TIMPs were
      detected in all fluids. In the operated animals, significantly (P <.05) higher
      activity of MMP-9 was found in amniotic fluid, with lower concentrations of TIMPs
      in allantoic fluid (P <.01). Tracheal occlusion was associated with a significant
      (P <.02) increase in both MMP-2 and -9 in tracheal fluid. CONCLUSION: Collagen
      plugging of the fetoscopic access port sites in sheep resulted in functionally
      effective sealing of the fetal membranes. Changes in MMP-2, MMP-9, and TIMPs
      suggest an active remodeling of both the fetal lung and the fetal membranes.

PMID- 12009388
TI  - Comparison of the responses to thrombin in monkey renal and uterine arteries.
AB  - OBJECTIVE: Thrombin is known to regulate vascular tone. We analyzed and compared
      mechanisms of thrombin action in primate renal and uterine arteries. METHODS:
      Isolated Japanese monkey renal and uterine arteries were suspended in Ringer
      Locke solution for tension recordings. RESULTS: Renal arteries responded to
      thrombin with relaxation, which was inhibited by N(G)-nitro-L-arginine or
      indomethacin and reversed to contractions by the combination. The relaxations
      were also reversed to contractions by endothelial denudation. Conversely,
      thrombin caused uterine arterial contractions that were unaffected by endothelial
      denudation. Relaxations in both renal arteries and contractions in uterine
      arteries were suppressed by hirudin (a specific thrombin inhibitor). Relaxant
      responses to A23187 (Ca(2+) ionophore), nitroprusside sodium (nitric oxide
      donor), and beraprost sodium (prostacyclin analogue) did not differ between renal
      and uterine arteries. CONCLUSION: Thrombin-induced relaxation of renal arteries
      appears to be mediated by nitric oxide and vasodilator prostaglandins liberated
      from the endothelium, whereas uterine arterial contraction is caused by an
      endothelium-independent mechanism.

PMID- 12009389
TI  - Association of umbilical placental vascular disease with fetal acute inflammatory
      cytokine responses.
AB  - OBJECTIVE: We examined the hypothesis that fetal proinflammatory cytokine release
      is a feature of placental vascular disease causing fetal compromise. We measured
      the concentrations of fetal proinflammatory cytokines interleukin 6 (IL-6), tumor
      necrosis factor alpha (TNF-alpha), and interleukin-8 (IL-8) in the presence of
      vascular disease in the umbilical placental villous circulation. Vascular disease
      was identified by high-resistance umbilical artery Doppler flow velocity waveform
      studies. METHODS: We measured levels of the inflammatory cytokines IL-6 and TNF
      alpha and the chemokine IL-8 in fetal blood. Blood was collected from the
      umbilical vein at delivery, and serum was stored at -70C until assayed using
      chemiluminescent and enzyme-linked immunosorbent assay methods. We studied 36
      normal pregnancies delivered by elective cesarean at term and 50 pregnancies with
      a high-resistance umbilical artery Doppler flow velocity waveform pattern
      indicative of fetal placental vascular disease delivered by elective cesarean
      because of potential fetal compromise. RESULTS: In the presence of umbilical
      placental vascular disease there were significantly higher levels of IL-6 (median
      5.3 pg/mL, P <.05) and IL-8 (median 26.5 pg/mL, P <.01) compared with normal
      pregnancies (median value of IL-6 and IL-8 were below assay threshold). There was
      no difference for TNF-alpha, with the median results undetectable in both groups.
      CONCLUSION: We found higher concentrations of IL-6 and IL-8 in the fetal
      circulation in the presence of umbilical placental vascular disease.

PMID- 12009390
TI  - Non-stress test changes during acupuncture plus moxibustion on BL67 point in
      breech presentation.
AB  - OBJECTIVES: We assessed fetal heart variability and activity using a computerized
      non-stress test (NST) during acupuncture plus moxibustion on the BL67 point. For
      comparison, the same changes were assessed during placebo acupuncture (minimal
      acupuncture) in the same subjects. METHODS: Twelve pregnant women in the 33rd
      week of gestation, carrying singletons in the breech presentation were enrolled
      in the study. In a single-blind design, each woman received a first session of
      minimal acupuncture followed 1-2 days later by true acupuncture. During the
      sessions, women were monitored using computerized non-stress testing starting 20
      minutes before the stimuli and continuing for 20 minutes after treatment.
      RESULTS: During true acupuncture a significant reduction in fetal baseline heart
      rate, and more accelerations and movement were observed. During minimal
      acupuncture, there were no significant changes in these variables. No signs of
      fetal distress or changes in short- or long-term variability were noted, and
      there were no uterine contractions. CONCLUSION: In our study population, acute
      application of acupuncture plus moxibustion did not cause fetal distress as
      assessed by either fetal heart rate decelerations or changes in either short- or
      long-term variability. Considering that the modifications in fetal movement and
      heart rate occurred in true but not during minimal acupuncture, we could consider
      that such changes are related to the effect of the acupuncture stimulation. The
      mechanisms leading to the cephalic version remain to be clearly established.

PMID- 12009391
TI  - Troglitazone: a possible modulator of ovarian steroidogenesis.
AB  - OBJECTIVE: Troglitazone increases insulin sensitivity. When used to treat women
      with insulin-resistant polycystic ovary syndrome (PCOS), troglitazone lowers
      androgen concentrations and improves ovulatory, endocrine, and metabolic
      disturbances. However, it is not known whether these effects are due to increased
      peripheral insulin sensitivity only or to direct effects on steroidogenesis. To
      determine whether troglitazone has a direct effect on ovarian steroidogenesis, we
      studied the effect of troglitazone on androgen production in cultured rat theca
      interstitial cells (rTICs) and on progesterone production in cultured human
      granulosa lutein cells (hGLCs). METHODS: Primary cell cultures of rTICs were
      isolated from the ovaries of hypophysectomized immature Sprague-Dawley rats, and
      hGLCs was obtained from women who had in vitro fertilization-embryo transfer.
      Treatments included troglitazone, insulin, LH, hCG, and combinations of these
      agents. Media were collected and assayed for androsterone and progesterone.
      RESULTS: Troglitazone decreased both basal and insulin-, LH-, and hCG-stimulated
      androsterone production by TIC and progesterone production by hGLCs in a dose
      dependent manner. CONCLUSION: We found a direct effect of troglitazone on the
      production of androsterone by rTICs and progesterone by hGLCs. These results
      suggest that the beneficial effects of troglitazone in PCOS may not be due solely
      to improvement of peripheral insulin resistance and hyperinsulinemia, but also to
      a possible direct effect on ovarian steroidogenesis.

PMID- 12009392
TI  - Effects of prostaglandin E(2) on proliferation and apoptosis of epithelial
      ovarian cancer cells.
AB  - OBJECTIVE: There is strong evidence indicating that prostaglandins (PG) and their
      synthesizing enzyme cyclooxygenase-2 (COX-2) play an important role in
      tumorigenesis. The purposes of the present study were to determine the pattern of
      expression of COX-2 and the effect of PG treatment on proliferation and apoptosis
      in epithelial ovarian cancer cells. METHODS: Two epithelial ovarian cancer cell
      lines, MDAH-2774 and SKOV3, were grown in flasks to confluence. Cells were then
      treated with exogenous dimethyl prostaglandin E(2) (dmPGE(2)) at increasing
      concentrations of 0-10 microg/mL. Total RNA was extracted from cells at different
      treatment doses and subjected to reverse transcriptase-polymerase chain reaction
      for the semiquantitative analysis of COX-2, Bcl-2, and bax expression. Flow
      cytometry was performed to assess effect of treatment on the cell cycle. The
      TUNEL assay was used to assess apoptosis. RESULTS: We found that COX-2 was
      constitutively expressed in the MDAH-2774 and SKOV3 epithelial ovarian cancer
      cells as determined by detection of a 304-bp amplified fragment using specific
      primers for the COX-2 gene. Treatment of both cell lines with dmPGE(2) resulted
      in dose-dependently higher expression of COX-2, Bcl-2, and bax mRNA compared with
      untreated cells. These changes were associated with an increase in the
      proliferative fraction and with a simultaneous reduction in apoptosis.
      CONCLUSIONS: Prostaglandin E(2) stimulated proliferation and reduced apoptosis in
      epithelial ovarian cancer cells. These effects were associated with
      overexpression of COX-2 and an increase in the ratio of Bcl-2:bax mRNA.

PMID- 12009394
TI  - Gonadotropins and the uterus: is there a gonad-independent pathway?

PMID- 12009393
TI  - Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian cancer:
      expression of coxsackie-adenovirus receptor and integrins alphavbeta3 and
      alphavbeta5.
AB  - OBJECTIVE: Ten patients with recurrent ovarian cancer received a combined
      treatment of optimal tumor debulking, adenovirus-mediated herpes simplex virus
      thymidine kinase gene therapy (GT), and systemic application of acyclovir or
      valacyclovir and topotecan. Biopsies were taken at the time of secondary
      debulking about 1 month after the application of GT and chemotherapy and were
      analyzed for expression of coxsackie-adenovirus receptor (CAR) and integrins
      alphavbeta3 and alphavbeta5 with respect to treatment response. METHODS:
      Treatment modalities and study design have been described recently.
      Immunohistochemistry was used to visualize expression of CAR and integrins
      alphavbeta3 and alphavbeta5 in tumor samples taken before and after application
      of GT. RESULTS: Before GT six of ten patients presented with CAR-positive and
      four with CAR-negative tumors. After GT all tumors showed CAR expression.
      Integrin alphavbeta3 was found in all tumors before and after GT. Expression of
      integrin alphavbeta5 was seen in eight of ten tumor samples before GT and in all
      samples after GT. CONCLUSION: Despite the importance of CAR and integrin
      expression for successful adenovirus internalization, other cell surface
      receptors might be involved in this process. It is too early to decide whether
      expressions of CAR and integrin alphavbeta3/alphavbeta5 on tumor cells are
      appropriate additional inclusion criteria for the enrollment of patients in GT
      trials. Further research is necessary to evaluate the effect of GT plus
      chemotherapy on CAR and integrin expression.

PMID- 12009396
TI  - Protein structural changes induced by their uptake at interfaces.
AB  - For insertion into lipidic media, most hydrosoluble proteins must cross the lipid
      water interface and thus undergo conformational transitions. According to their
      chemical sequences these transitions may be restricted to changes involving only
      the tertiary structure, while for other proteins this environment modification
      will induce drastic changes such as the unfolding of large domains. The
      structural transitions are mainly governed by the presence of hydrophobic domains
      and/or by the existence of induced amphipathic properties.

PMID- 12009397
TI  - Temperature-induced beta-aggregation of fibronectin in aqueous solution.
AB  - Fibronectin structural reorganization induced by temperature has been
      investigated by Fourier-transform infrared (FT-IR) spectroscopy and light
      scattering experiments. At 20 degrees C, from resolution enhanced by FT-IR
      spectra, 43% of beta sheet, 31% of turn and 26% of unordered structures were
      estimated. Static and quasi-elastic light-scattering results do not change
      significantly between 20 and 34 degrees C. Just below 50 degrees C, a decrease of
      1/3 of beta sheet structures contents is observed, concomitantly with a
      corresponding increase of turn. The contribution of disordered structures is
      found to be temperature-independent. Above 50 degrees C, our data reveals the
      formation of intermolecular hydrogen bonding leading to the formation of
      intermolecular beta sheet structures. The IR band absorption at 1618 cm(-1)
      increases strongly as a function of temperature. The scattered intensity
      increases and becomes strongly q(2)-dependent. The dynamic structure factor is
      not a single exponential decay and becomes strongly dependent on the scattering
      angle. These results demonstrate that aggregation occurs in fibronectin solution.
      When temperature decreases, this aggregation is found irreversible. Fibronectin
      aggregation is driven by the formation of intermolecular hydrogen bonds
      responsible for intermolecular beta sheet structures.

PMID- 12009398
TI  - Thermodynamic properties of nucleotide-free EF-Tu from Thermus thermophilus in
      the presence of low-molecular weight effectors of its GTPase activity.
AB  - The thermal transition of elongation factor EF-Tu from Thermus thermophilus in
      the presence of low-molecular weight effectors was studied by differential
      scanning calorimetry. The effectors of GTPase activity used were the antibiotic
      kirromycin and the cations Li(+), Na(+), K(+) and NH(4)(+) in the chloride form.
      The temperature of thermal denaturation and the cooperativity of the transition
      of nucleotide-free EF-Tu (EF-Tu(f)) in the presence of kirromycin are comparable
      with those of the EF-Tu x guanosine-5'-[beta,gamma-imido]triphosphate (GppNHp)
      form, indicating similar conformational states. Increased concentrations of Na(+)
      and K(+) stabilized EF-Tu(f) in a manner similar to GppNHp. NH(4)(+) decreased
      the transition temperature of EF-Tu(f) and Li(+) decreased both the temperature
      and the calorimetric enthalpy of the thermal transition of EF-Tu(f). In the
      presence of salts, binding of kirromycin had a stabilizing effect on EF-Tu(f).
      Correlation between the GTPase activity and thermodynamic characteristics of EF
      Tu(f) induced by kirromycin in the absence or presence of the cations is
      discussed.

PMID- 12009399
TI  - Solvent-dependent precipitation of prion protein.
AB  - The misfolded isoform of the prion protein (PrP(Sc)) possesses many unusual
      physiochemical properties. Previously, we and others reported on the differential
      partitioning of PrP(Sc) from plasma derived therapeutic proteins during their
      purification processes. To understand the driving force behind these partitioning
      differences, we investigated the effects of various solvent conditions on the
      precipitation of PrP(Sc). In a physiological buffer, PrP(Sc) remained in the
      supernatant after low speed centrifugation. At pH 5, PrP(Sc) precipitation was
      nearly complete regardless of the salt content. PrP(Sc) could also be
      precipitated at pH 8 by adding ethanol, but this precipitation was salt
      dependent. Based on these observations, an empirical mathematical model was
      constructed in which the PrP(Sc) precipitation trends were fully described as a
      function of solvent pH, salt, and ethanol concentration. This model consistently
      predicted PrP(Sc) partitioning during cold ethanol precipitation steps used in
      plasma protein purification processes, as shown by experimentally determined
      distributions of PrP(Sc) and transmissible spongiform encephalopathy (TSE)
      infectivity. These results indicate that pH, salt, and ethanol content are the
      major solvent factors determining the precipitation of the infectious PrP(Sc) in
      these processes and may provide a useful tool for assessing the differential
      partitioning of PrP(Sc) in a given solvent environment.

PMID- 12009400
TI  - The distinctiveness of ATP:citrate lyase from Aspergillus nidulans.
AB  - ATP:citrate lyase (ACL), an important enzyme in lipid synthesis, has been
      purified from Aspergillus nidulans to a specific activity of 19.6 micromol min(
      1) mg(-1), almost twice that of any other purified ACL and shown to be distinct
      from any previously purified ACL. The enzyme is a 371+/-31 kDa hexamer of 3
      alpha, 3 beta proteins, unlike the 4 alpha tetramer found in rats or yeasts. The
      molecular weights of the alpha and beta protein subunits were determined by SDS
      PAGE to be 70 and 55 kDa. ACL in A. nidulans (unlike Aspergillus niger) appears
      to be regulated by the carbon source present in the media. In crude extracts, it
      was found at high activity (88 micromol min(-1) mg protein(-1)) in glucose-grown
      cells but only at low activity (10 micromol min(-1) mg protein(-1)) in acetate
      grown cells.

PMID- 12009401
TI  - Guanidinium chloride induced unfolding of a hemocyanin subunit from Carcinus
      aestuarii. I. Apo form.
AB  - The effects of guanidinium chloride (GuHCl) on the stability of the apo form of
      the 5S non-reassociating subunit of hemocyanin from the crab Carcinus aestuarii
      (apo-CaeSS2) were investigated, using a variety of optical spectroscopy
      techniques (light scattering (LS), fluorescence (IF and EF) and circular
      dichroism (CD)). The fluorescence of 8-anilino-1-naphtalene sulphonate (ANS) was
      strongly enhanced in the presence of apo-CaeSS2, in contrast to holo-CaeSS2,
      suggesting the formation of a molten globule (MG)-like state, consequent to the
      removal of the two copper ions from the holo subunit. Other evidences, favouring
      the presence of this state in apo-CaeSS2, derive from an enhanced quenching of
      intrinsic fluorescence (IF) by acrylamide, a higher sensibility towards
      aggregation and a higher IF with respect to deoxy holo-CaeSS2. Aggregation of apo
      CaeSS2 below 1.2 M GuHCl was detected by LS, suggesting the formation of an
      aggregation-prone intermediate, called I1. Due to this effect, fluorescence and
      CD data could only be collected above that denaturant concentration. Both IF
      (protein) and EF (ANS) fluorescence data were best fitted by a two-state
      cooperative transition, occurring between the intermediate I1 and the unfolded
      state U, with C(1/2) 1.6-1.7 M. A similar two-state transition, with a slightly
      higher C(1/2) value (1.9 M), was also inferred from far-UV CD data, suggesting
      the possible formation of another intermediate. Partial refolding of apo-CaeSS2
      by dilution was found to occur above 1.2 M GuHCl, i.e. up to the level of I1,
      since at lower denaturant concentration protein aggregation took place, as also
      observed in unfolding. All thermodynamic parameters, derived from data above 1.2
      M GuHCl, are therefore referred to transitions between intermediate and unfolded
      states only. Unfolding kinetics, followed by fluorescence stopped-flow, was
      biphasic in the whole GuHCl range investigated (3-5 M), suggesting the formation
      of a transient intermediate, possibly related to that observed under equilibrium
      conditions.

PMID- 12009402
TI  - Guanidinium chloride induced unfolding of a hemocyanin subunit from Carcinus
      aestuarii. II. Holo form.
AB  - The effects of guanidinium hydrochloride (GuHCl) on the functional and structural
      properties of a 75-kDa, functionally active hemocyanin (Hc) subunit isolated from
      the crab Carcinus aestuarii (holo-CaeSS2) were investigated. The holo form of the
      protein contains two copper ions in the active site and is capable of reversibly
      binding dioxygen. The present results are compared with those previously
      described for the corresponding functionally inactive subunit (apo-CaeSS2),
      devoid of the two active site copper ions (accompanying paper [R. Favilla, M.
      Goldoni, A. Mazzini, M. Beltramini, P. Di Muro, B. Salvato, paper published in
      this issue]). As with apo-CaeSS2, both equilibrium and kinetic unfolding
      measurements were carried out using light scattering (LS), circular dichroism,
      intrinsic and extrinsic fluorescence (IF and EF, respectively). In addition here,
      absorbance spectroscopy was exploited to evaluate oxygen binding by holo-CaeSS2.
      These data were combined with those relative to the protein copper content to
      obtain information on the stability of the active site as a function of
      denaturant concentration. The different techniques used revealed several
      unfolding transitions. At GuHCl<1 M, an appreciable increase of LS intensity was
      observed, about an order of magnitude lower than with apo-CaeSS2, suggesting some
      reversible protein aggregation. A first cooperative transition as a function of
      GuHCl was detected as an increase of intensity of the protein IF (C(1/2)=1 M),
      followed by a second transition, characterised by a small intensity decrease and
      a red shift of the emission maximum (C(1/2)=1.4 M). Cooperative transitions with
      C(1/2) values near 1.4 M GuHCl were also detected by following the decrement of:
      (a) EF intensity of anilino-1-naphtalenesulphonate (ANS) bound to the protein;
      (b) absorbance at 340 nm, typical of oxy holo-CaeSS2; (c) copper-to-protein
      stoichiometry. A transition at higher GuHCl (C(1/2)=1.8 M) was also observed by
      far UV circular dichroism (far UV CD) and related to global unfolding. Unfolding
      kinetics was also studied using the fluorescence stopped-flow technique. All
      traces were best fitted by a sum of three or four exponential terms, depending on
      GuHCl concentration. A comprehensive unfolding model is proposed, which accounts
      for most of the complex behaviour of this protein subunit, including oxy and
      deoxy native and aggregation-prone intermediates, a highly fluorescent
      intermediate, molten globule-like apo and unfolded species.

PMID- 12009403
TI  - Fluorescent inhibitors reveal solvent-dependent micropolarity in the lipid
      binding sites of lipases.
AB  - Triacylglycerol analogue p-nitrophenyl phosphonates specifically react with the
      active-site serine of lipolytic enzymes to give covalent lipase-inhibitor
      complexes, mimicking the first transition state which is involved in lipase
      mediated ester hydrolysis. Here we report on a new type of phosphonate inhibitors
      containing a polarity-sensitive fluorophore to monitor micropolarity around the
      active site of the enzyme in different solvents. The respective compounds are
      hexyl and methyl dimethylamino-naphthalenecarbonylethylmercaptoethoxy
      phosphonates. The hexyl phosphonate derivative was reacted with lipases from
      Rhizopus oryzae (ROL), Chromobacterium viscosum (CVL), and Pseudomonas cepacia
      (PCL). The resulting lipid-protein complexes were characterized in solution with
      respect to water penetration into the lipid binding site and the associated
      conformational changes of the proteins as a consequence of solvent polarity
      changes. We found that the accessibility of the lipid-binding site in all lipases
      studied was lowest in water. It was much higher when the protein was dissolved in
      aqueous ethanol. These biophysical effects may contribute to the previously
      observed dramatic changes of enzyme functions such as activity and
      stereoselectivity depending on the respective solvents.

PMID- 12009404
TI  - Sequential inactivation of zeta-crystallin by o-phthalaldehyde.
AB  - o-Phthalaldehyde, a bifunctional cross-linking reagent, is commonly used as a
      probe for the active site of enzymes. In this study, the interaction of o
      phthalaldehyde with camel lens zeta-crystallin was examined by activity and
      fluorescence measurements. Predictably, the oxidoreductase activity of zeta
      crystallin was inhibited irreversibly by o-phthalaldehyde in a time- and
      concentration-dependent manner, and the presence of NADPH with the enzyme
      appeared to provide a high degree of protection against o-phthalaldehyde
      inactivation. Interaction of o-phthalaldehyde with zeta-crystallin resulted in
      formation of isoindole adduct, which exhibited characteristic fluorescence at 415
      nm. However, neither inactivation nor modification of the enzyme showed the
      expected pseudo-first-order kinetics; both events were highly sequential reaching
      different levels of saturation at different concentrations of o-phthalaldehyde.
      The modified enzyme had a maximum stoichiometry of 1 mol isoindole/subunit, and
      bound NADPH to nearly the same extent as unmodified enzyme. Gel filtration
      experiments suggested that o-phthalaldehyde-modified zeta-crystallin had higher
      apparent molecular weight than unmodified enzyme, even though the enzyme remained
      largely monomeric as revealed by electrophoresis on denaturing gel. These results
      suggested that modification by o-phthalaldehyde might have been so intrusive as
      to sequentially modify the tetrameric structure of zeta-crystallin.

PMID- 12009405
TI  - Substrate recognition by 2-oxoacid:ferredoxin oxidoreductase from Sulfolobus sp.
      strain 7.
AB  - 2-Oxoacid:ferredoxin oxidoreductase (OFOR) catalyzes the coenzyme A-dependent
      oxidative decarboxylation of 2-oxoacids, at an analogous metabolic position to 2
      oxoacid dehydrogenase multienzyme complex. The enzyme from Sulfolobus sp. strain
      7, a thermoacidophilic crenarchaeon, is a heterodimer comprising two subunits, a
      (632 amino acids) and b (305 amino acids). In contrast to other OFORs, the
      Sulfolobus enzyme shows a broad specificity for 2-oxoacids such as pyruvate and 2
      oxoglutarate. Based on careful multiple alignment of this enzyme family and on
      the reported three-dimensional structure of the homodimeric pyruvate:ferredoxin
      oxidoreductase (POR) from Desulfovibrio africanus, we selected five amino acids,
      T256, R344 and T353 of subunit-a, and K49 and L123 of subunit-b, as candidate 2
      oxoacid recognizing residues. To identify the residues determining the 2-oxoacid
      specificity of the enzyme family, we performed point mutations of these five
      amino acids, and characterized the resulting mutants. Analyses of the mutants
      revealed that R344 of subunit-a of the enzyme was essential for the activity, and
      that K49R and L123N of subunit-b drastically affected the enzyme specificity for
      pyruvate and 2-oxoglutarate, respectively. Replacement of the five residues
      resulted in significant changes in both K(m) and V(max), indicating that these
      amino acids are clearly involved in substrate recognition and catalysis.

PMID- 12009406
TI  - A new syringopeptin produced by bean strains of Pseudomonas syringae pv.
      syringae.
AB  - Two strains (B728a and Y37) of the phytopathogenic bacterium Pseudomonas syringae
      pv. syringae isolated from bean (Phaseolus vulgaris) plants were shown to produce
      in culture both syringomycin, a lipodepsinonapeptide secreted by the majority of
      the strains of the bacterium, and a new form of syringopeptin, SP(22)Phv. The
      structure of the latter metabolite was elucidated by the combined use of mass
      spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy and chemical
      procedures. Comparative phytotoxic and antimicrobial assays showed that SP(22)Phv
      did not differ substantially from the previously characterized syringopeptin 22
      (SP(22)) as far as toxicity to plants was concerned, but was less active in
      inhibiting the growth of the test fungi Rhodotorula pilimanae and Geotrichum
      candidum and of the Gram-positive bacterium Bacillus megaterium.

PMID- 12009407
TI  - The importance of cysteine 126 in the human liver UDP-glucuronosyltransferase
      UGT1A6.
AB  - The human UDP-glucuronosyltransferase 1A6 (UGT1A6) isoform is actively involved
      in the detoxication of phenolic compounds. In an effort to gain insight on active
      site amino acids, we investigated the functional relevance of cysteinyl residues
      in the glucuronidation process. The enzyme was irreversibly inactivated upon
      exposure to thiol-specific reagents, especially N-phenylmaleimide. Site-directed
      mutagenesis of the conserved Cys126 into valine led to a fully inactive mutant,
      whereas conservative substitution with serine significantly restored the
      glucuronidation activity toward 4-methylumbelliferone used as a reference
      substrate. This mutant exhibited a reduced affinity toward the acceptor
      substrate, as evidenced by a 10-times increase in K(m) value, compared to the
      wild-type enzyme. The two mutations did not alter the stability of UGT1A6 nor
      change the subcellular localization of the protein in the endoplasmic reticulum
      of recombinant cells. These results support the conclusion that Cys126 is an
      essential residue for the integrity of the substrate binding site of UGT1A6.

PMID- 12009408
TI  - Immunoaffinity purification of calpastatin and calpastatin constructs.
AB  - It has been difficult to purify calpastatin without using a step involving
      heating to 90-100 degrees C. Preparations of calpastatin obtained after heating
      often contain several polypeptides that have been ascribed to proteolytic
      degradation. Because calpastatin is highly susceptible to proteolytic degradation
      and several different calpastatin isoforms can be produced by using different
      start sites of transcription/translation and/or alternative splicing from the
      single calpastatin gene, it is not clear whether the different polypeptides
      observed in purified calpastatin preparations are proteolytic fragments or
      calpastatin isoforms. It would be useful, therefore, to have a method for
      purifying calpastatin that does not involve heating. At low ionic strength,
      calpastatin from skeletal muscle extracts binds quantitatively to an
      immunoaffinity column made by coupling a monoclonal antibody (MAb) to the C
      terminal end of calpastatin (epitope between amino acids 707 and 786) to agarose;
      the bound calpastatin can be eluted at pH 2.5. The C-terminal end of the
      calpastatin polypeptide was used because the known isoforms of calpastatin all
      contain domain IV. The eluted calpastatin, which retains all its calpain
      inhibitory activity, consists largely of a 125 kDa polypeptide (70%), and several
      smaller polypeptides that are labeled with a MAb to calpastatin. Expressed
      calpastatin constructs representing the full-length XL-IV calpastatin and domains
      L-IV, II-IV, III-IV, and IV also bind to the immunoaffinity column and can be
      purified. The immunoaffinity column is especially useful for purifying
      calpastatin from small tissue samples in a single step.

PMID- 12009409
TI  - Conformational change of the N-domain on formation of the complex between the
      GTPase domains of Thermus aquaticus Ffh and FtsY.
AB  - The structural basis for the GTP-dependent co-translational targeting complex
      between the signal recognition particle (SRP) and its receptor is unknown. The
      complex has been shown to have unusual kinetics of formation, and association in
      vivo is likely to be dependent on catalysis by the SRP RNA. We have determined
      conditions for RNA-independent association of the 'NG' GTPase domains of the
      prokaryotic homologs of the SRP components, Ffh and FtsY, from Thermus aquaticus.
      Consistent with previous studies of the Escherichia coli proteins, the kinetics
      of association and dissociation are slow. The T. aquaticus FtsY is sensitive to
      an endogenous proteolytic activity that cleaves at two sites--the first in a
      lengthy linker peptide that spans the interface between the N and G domains, and
      the second near the N-terminus of the N domain of FtsY. Remarkably, this second
      cleavage occurs only on formation of the Ffh/FtsY complex. The change in protease
      sensitivity of this region, which is relatively unstructured in the FtsY but not
      in the Ffh NG domain, implies that it undergoes conformational change on
      formation of the complex between the two proteins. The N domain, therefore,
      participates in the interactions that mediate the GTP-dependent formation of the
      targeting complex.

PMID- 12009410
TI  - Recognition of HNA and 1,5-anhydrohexitol nucleotides by DNA metabolizing
      enzymes.
AB  - Hexitol nucleic acids (HNA) as well as their 1,5-anhydrohexitol triphosphate
      building blocks were evaluated for their ability to be recognized by several DNA
      metabolizing enzymes. It was found that RNA polymerases can recognize the
      triphosphate of the adenine analogue. However, only the incorporation of a
      maximum of three consecutive building block analogues was possible under the
      applied experimental conditions. Terminal transferase was more successful
      succeeding in the elongation of a DNA primer with a maximum of 15 1,5
      anhydrohexitol purine nucleotides. Furthermore, it was observed that the 1,5
      anhydroaltritol triphosphate analogue of adenosine was a poor substrate for
      terminal transferase and that HNA could not act as a primer for this enzyme.
      Likewise, HNA did not function as a template for restriction enzymes, ligases or
      methylases.

PMID- 12009411
TI  - Purification and characterization of ferredoxin-NAD(P)(+) reductase from the
      green sulfur bacterium Chlorobium tepidum.
AB  - Ferredoxin-NAD(P)(+) reductase [EC 1.18.1.3, 1.18.1.2] was isolated from the
      green sulfur bacterium Chlorobium tepidum and purified to homogeneity. The
      molecular mass of the subunit is 42 kDa, as deduced by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The molecular mass of the native
      enzyme is approximately 90 kDa, estimated by gel-permeation chromatography, and
      is thus a homodimer. The enzyme contains one FAD per subunit and has absorption
      maxima at about 272, 385, and 466 nm. In the presence of ferredoxin (Fd) and
      reaction center (RC) complex from C. tepidum, it efficiently catalyzes
      photoreduction of both NADP(+) and NAD(+). When concentrations of NADP(+)
      exceeded 10 microM, NADP(+) photoreduction rates decreased with increased
      concentration. The inhibition by high concentrations of substrate was not
      observed with NAD(+). It also reduces 2,6-dichlorophenol-indophenol (DPIP) and
      molecular oxygen with either NADPH or NADH as efficient electron donors. It
      showed NADPH diaphorase activity about two times higher than NADH diaphorase
      activity in DPIP reduction assays at NAD(P)H concentrations less than 0.1 mM. At
      0.5 mM NAD(P)H, the two activities were about the same, and at 1 mM, the former
      activity was slightly lower than the latter.

PMID- 12009412
TI  - Reactivation of immobilized acetyl cholinesterase in an amperometric biosensor
      for organophosphorus pesticide.
AB  - Biosensors based on acetyl cholinesterase (AChE) inhibition have been known for
      monitoring of pesticides in food and water samples. However, strong inhibition of
      the enzyme is a major drawback in practical application of the biosensor which
      can be overcome by reactivation of the enzyme for repeated use. In the present
      study, enzyme reactivation by oximes was explored for this purpose. Two oximes
      viz., 1,1'-trimethylene bis 4-formylpyridinium bromide dioxime (TMB-4) and
      pyridine 2-aldoxime methiodide (2-PAM) were compared for the reactivation of the
      immobilized AChE. TMB-4 was found to be a more efficient reactivator under
      repeated use, retaining more than 60% of initial activity after 11 reuses,
      whereas in the case of 2-PAM, the activity retention dropped to less than 50%
      after only 6 reuses. Investigations also showed that reactivation must be
      effected within 10 min after each analysis to eliminate the ageing effect, which
      reduces the efficiency of reactivation.

PMID- 12009413
TI  - Mechanistic implications of variable stoichiometries of oxygen consumption during
      tyrosinase catalyzed oxidation of monophenols and o-diphenols.
AB  - The stoichiometry of oxygen consumption during tyrosinase-catalyzed oxidation of
      an o-diphenol (4-tert-butylcatechol, TBC) and a monophenol (4-tert-butylphenol,
      TBP) has been determined. At high [substrate]/[enzyme] ratios, in the case of o
      diphenols, the stoichiometry of the enzyme-catalyzed reaction was always 1 O(2)/2
      o-diphenols, although if the o-quinone product was unstable, the apparent
      stoichiometry could tend to 1 O(2)/1 o-diphenol due to regeneration of an o
      diphenol in a side reaction. In the case of monophenols, the stoichiometry could
      be 1 O(2)/1 monophenol or 1.5 O(2)/1 monophenol depending if the o-quinone
      product was stable or unstable, respectively. However, at low
      [substrate]/[enzyme] ratios, the oxygen/substrate stoichiometry could, even in
      the case where stable products are formed, be lower than 1 O(2)/2 substrates for
      o-diphenols or higher than 1 O(2)/1 substrate for monophenols. These data
      supported the mechanism proposed by Rodriguez-Lopez et al. [J. Biol. Chem. 267
      (1992) 3801-3810], in which, during hydroxylation of monophenols, tyrosinase
      first transformed monophenol to o-diphenol and then either catalyzed a further
      oxidation to form o-quinone or released it into the reaction medium. In this
      second case, subsequent oxidation of the o-diphenol resulted in additional oxygen
      consumption.

PMID- 12009414
TI  - Differences in natural ligand and fluoropyrimidine binding to human thymidylate
      synthase identified by transient-state spectroscopic and continuous variation
      methods.
AB  - Thymidylate synthase (TS) is a central target for the design of chemotherapeutic
      agents due to its vital role in DNA synthesis. Structural studies of binary
      complexes between Escherichia coli TS and various nucleotides suggest the
      chemotherapeutic agent FdUMP and the natural ligand dUMP bind similarly. We show,
      however, that FdUMP binding to human TS yields a substantially greater decrease
      in fluorescence than does dUMP. Because the difference in quenching due to ligand
      binding was approximately two-fold and this difference was not seen when using
      ecTS, the intriguing result indicated a significant difference in the mode of
      FdUMP binding to the human enzyme. We compared the binding affinities of dUMP,
      FdUMP, and TMP to TS from both species and found no significant differences for
      the individual ligands. Because binding affinities were not different among the
      ligands, the method of continuous variation was employed to determine binding
      stoichiometry. Similar to that found for dUMP binding to human and ecTS, FdUMP
      displayed single site occupancy with both enzymes. These results show that
      nucleotide binding differences exist for FdUMP and dUMP binding to the human
      enzyme. The observed differences are not due to differences in stoichiometry or
      ligand affinity. Therefore, although the crystal structure of human TS with
      various nucleotide ligands has not been solved, these results show that the
      differences observed using fluorescence methods result from as yet unidentified
      differential interactions between the human enzyme and nucleotide ligands.

PMID- 12009415
TI  - Aromatic residues in the C-terminal region of glutathione transferase A1-1
      influence rate-determining steps in the catalytic mechanism.
AB  - Human glutathione transferase A1-1 (GST A1-1) has a flexible C-terminal segment
      that forms a helix (alpha 9) closing the active site upon binding of glutathione
      and a small electrophilic substrate such as 1-chloro-2,4-dinitrobenzene (CDNB).
      In the absence of active-site ligands, the C-terminal segment is not fixed in one
      position and is not detectable in the crystal structure. A key residue in the
      alpha 9-helix is Phe 220, which can interact with both the enzyme-bound
      glutathione and the second substrate, and possibly guide the reactants into the
      transition state. Mutation of Phe 220 into Ala and Thr was shown to reduce the
      catalytic efficiency of GST A1-1. The mutation of an additional residue, Phe 222,
      caused further decrease in activity. The presence of a viscosogen in the reaction
      medium decreased the kinetic parameters K(cat) and K(cat)/K(m) for the
      conjugation of CDNB catalyzed by wild-type GST A1-1, in agreement with the view
      that product release is rate limiting for the substrate-saturated enzyme. The
      mutations cause a decrease of the viscosity dependence of both kinetic
      parameters, indicating that the motion of the alpha 9-helix is linked to
      catalysis in wild-type GST A1-1. The isomerization reaction with the alternative
      substrate Delta(5)-androstene-3,17-dione (AD) is affected in a similar manner by
      the viscosogens. The transition state energy of the isomerization reaction, like
      that of the CDNB conjugation, is lowered by Phe 220 as indicated by the effects
      of the mutations on K(cat)/K(m). The results demonstrate that Phe 220 and Phe
      222, in the dynamic C-terminal segment, influence rate-determining steps in the
      catalytic mechanism of both the substitution and the isomerization reactions.

PMID- 12009416
TI  - Multi-step analysis as a tool for kinetic parameter estimation and mechanism
      discrimination in the reaction between tight-binding fasciculin 2 and electric
      eel acetylcholinesterase.
AB  - The mechanism of action of a potent peptidic inhibitor fasciculin 2 (Fas2) on
      electric eel acetylcholinesterase (eleelAChE) has been examined in a three-level
      analysis. Classical steps included equilibration experiments for the evaluation
      of high affinity binding constant and the existence of residual hydrolytic
      activity in a solution of completely Fas2 saturated enzyme. The two rate
      constants for the association (k(on)) and the dissociation (k(off)) of Fas2 with
      free enzyme were determined by the time course of residual enzyme activity
      measurements. In the third step, with a nonclassical progress curve analysis, we
      found that the Fas2-enzyme complex exhibited hydrolytic activity in a
      butyrylcholinesterase-like kinetics. The switch appears to be a consequence of
      steric obstruction, but also the consequence of subtle rapid conformational
      changes around catalytic site, upon slow single-step binding of large Fas2
      molecule at the peripheral site. An unusual unilateral effect of bound Fas2 is
      reflected by acylation-independent association and dissociation rates and might
      indeed be due to inability of small acylation agent to influence the binding of a
      large opponent.

PMID- 12009417
TI  - Gene repair and mutagenesis mediated by chimeric RNA-DNA oligonucleotides:
      chimeraplasty for gene therapy and conversion of single nucleotide polymorphisms
      (SNPs).
AB  - Gene augmentation is an attractive and viable approach in treatment of inherited
      diseases, despite its limitations, such as the eliciting of host immune response,
      and the sustainability of gene expression. Therefore, alternative therapeutic
      approaches are being investigated, such as the use of chimeric RNA-DNA
      oligonucleotides (chimeraplasts), in which a mutated allele that already exists
      in an affected individual can be corrected. Although the only gene defects that
      can be corrected by chimeraplasty are point mutations, and the correction
      frequencies are variable, it has been observed that intracellular delivery of
      oligonucleotides is likely to be more efficient than that of plasmid DNA or viral
      vectors. Furthermore, corrected genes are expressed from their autologous
      promoters, thus ensuring correct spatial and temporal expression. Here we report
      on the recent progress made in the field of chimeraplasty, and the problems
      encountered.

PMID- 12009418
TI  - A "de novo" mutation of the LDL-receptor gene as the cause of familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is a common genetic disorder caused by
      mutations of the LDL-receptor gene and transmitted as a co-dominant trait.
      However, there are some forms of hypercholesterolemia which have a recessive type
      of transmission. We have identified a subject with the clinical phenotype of
      heterozygous FH whose parents had normal plasma lipid values, suggesting a
      recessive type of transmission. The analysis of the LDL-receptor gene revealed
      that the patient was heterozygous for a G>C transversion in exon 4, which results
      in a serine for cysteine substitution at position 88 (C88S) of the receptor
      protein. Since this novel mutation was not found in the proband's parents and non
      paternity was excluded, we concluded that the patient was a carrier of a "de
      novo" mutation. Haplotype analysis of LDL-receptor locus indicated that this "de
      novo" mutation occurred in the paternal germ line. The C88S mutation is the
      likely cause of LDL-receptor defect as it was present in the proband's
      hypercholesterolemic son and was not found in 200 chromosomes of control
      subjects.

PMID- 12009419
TI  - Hepatotoxicity and aging: endogenous antioxidant systems in hepatocytes from 2-,
      6-, 12-, 18- and 30-month-old rats following a necrogenic dose of thioacetamide.
AB  - The influence of aging on the mechanisms of liver injury and regeneration was
      studied in a model of hepatotoxicity induced in 2-, 6-, 12-, 18- and 30-month-old
      rats by a sublethal dose of thioacetamide (500 mg/kg body weight), a soft
      nucleophilic and hepatotoxic compound metabolized by the hepatic microsomal FAD
      monooxygenase system. Samples-blood and hepatocytes-were obtained at 0, 12, 24,
      48, 72 and 96 h following thioacetamide intoxication. Parameters of liver injury
      in serum (NADPH-isocitrate dehydrogenase (ICDH) activity) indicate that the
      severity of injury was significantly higher in the adult groups (6 and 12 months
      old) when compared either with the youngest (2 months old) or oldest (18 and 30
      months old) groups. Parameters related to biotransformation, such as microsomal
      FAD monooxygenase, followed mainly the same pattern of age-dependent changes as
      those observed for injury. The profile of glutathione-S-transferase activity
      showed an initial induction parallel to liver injury and opposite to the levels
      of reduced glutathione and protein -SH groups. Enzyme activities and gene
      expression of the systems involved in the cell endogenous antioxidant defense,
      such as Mn- and Cu,Zn-superoxide dismutases (SOD), catalase and glutathione
      peroxidase (GPX) showed significant age-dependent changes that can be summarized
      as follows: an increase in all enzyme activities and gene expression and a
      decreased ability to restore the initial activities following 96 h of
      thioacetamide. We conclude, first, that the gene expression and activity of the
      enzymes involved in the intracellular antioxidant defense system increased with
      aging, which can be considered a consequence of the enhanced oxidative state of
      the cell (decreased in GSH level); and second, that the lower and delayed
      response in the aged groups significantly influenced the restoration towards
      normal of GSH and the antioxidant enzyme activities.

PMID- 12009420
TI  - On the regulatory role of dipeptidyl peptidase IV (=CD=adenosine deaminase
      complexing protein) on adenosine deaminase activity.
AB  - The molecular mechanism controlling the variable activity of the malignancy
      marker adenosine deaminase (ADA) is enigmatic. ADA activity was found to be
      modulated by the membrane-bound adenosine deaminase complexing protein
      (CP=DPPIV=CD26). The role of lipid-protein interactions in this modulation was
      sought. While direct solubilization of ADA in vesicles resulted in loss of ADA
      activity, the binding of ADA to CP reconstituted in vesicles restored the
      specific activity. The activity of ADA, free or bound to CP in solution, resulted
      in continuous linear Arrhenius plots. However, ADA bound to reconstituted CP
      exhibited two breaks associated with approximately 30% increased activity, at 25
      and 13 degrees C, yielding three lines with similar apparent activation energies
      (E(a)). Continuum solvent model calculations of the free energy of transfer of
      the transmembrane helix of CP from the aqueous phase into membranes of various
      widths show that the most favorable orientations of the helix above and below the
      main phase transition may be different. We suggest that the 20% change in the
      thickness of the bilayer below and above the main phase transition may modify the
      orientation of CP in the membrane, thereby affecting substrate accessibility of
      ADA. This could account for ADA's reduced activity associated with increased
      membrane fluidity in transformed vs. normal fibroblasts.

PMID- 12009421
TI  - Protective effects of ibuprofen and its major metabolites against in vitro
      inactivation of catalase and fumarase: relevance to cataract.
AB  - Ibuprofen and its major metabolites were incubated with catalase and fumarase, in
      the presence of protein-modifying biomolecules, to explore the mode of action of
      ibuprofen in protection against cataract. Both 2 and 10 mM ibuprofen/metabolites
      protected catalase against fructose-, cyanate- and prednisolone-induced
      inactivation; the carboxy-metabolite gave the highest protection (31%). The 2 mM
      ibuprofen/metabolites protected fumarase against fructose- and cyanate-induced
      inactivation by up to 26%, but had no effect on prednisolone-induced
      inactivation. Ibuprofen/metabolites did not bind to catalase or fumarase. They
      penetrated into the lens in vitro. When in the lens, the metabolites may reduce
      the risk of cataract by protecting lenticular enzymes.

PMID- 12009422
TI  - Expression of endoglin in human mesangial cells: modulation of extracellular
      matrix synthesis.
AB  - Transforming growth factor-beta (TGF-beta) has been identified as a key mediator
      of glomerulosclerosis in kidney diseases. Endoglin is a component of the TGF-beta
      receptor system that is upregulated during glomerulosclerosis, suggesting a role
      during progression of renal diseases characterized by extracellular matrix (ECM)
      synthesis and accumulation. The expression of endoglin was demonstrated in
      cultured human mesangial cells (HMC) by flow cytometry, Northern blot, reverse
      transcriptase polymerase chain reaction (RT-PCR), and Western blot analyses. TGF
      beta upregulated not only the expression of endoglin, but also that of TGF-beta
      itself, TGF-beta receptor type II, collagen I, collagen IV, and fibronectin. To
      study the role of endoglin in TGF-beta responses, transfectant fibroblasts
      overexpressing endoglin were analyzed. Untreated and TGF-beta-treated endoglin(+)
      cells showed significantly lower levels of collagens than those in control cells,
      indicating that endoglin negatively regulates ECM levels of collagens. These
      findings may have important implications in the pathological states associated
      with renal fibrosis.

PMID- 12009423
TI  - Biochemical and molecular study of mentally retarded patient with partial
      deficiency of hypoxanthine-guanine phosphoribosyltransferase.
AB  - Nucleotide metabolism was studied in erythrocytes of a mentally retarded child
      and family members. Partial hypoxanthine-guanine phosphoribosyltransferase (HPRT)
      deficiency was found in the propositus and an asymptomatic maternal uncle.
      Studies in crude lysates demonstrated decreased apparent V(max) and slightly
      decreased apparent K(m) for hypoxanthine in both HPRT-deficient subjects. Genomic
      DNA analysis revealed a single nucleotide change with leucine-147 to
      phenylalanine substitution in both subjects; mother and grandmother were
      heterozygous carriers of the same defect. This new variant has been termed
      HPRT(Potenza). Increased erythrocyte concentration of NAD and rate of synthesis
      by intact erythrocytes were found in the patient; increased activities of
      nicotinic acid phosphoribosyltransferase (NAPRT) and NAD synthetase (NADs) were
      demonstrated in erythrocyte lysates, with normal apparent K(m) for their
      substrates and increased V(max). These alterations were not found in any member
      of the family, including the HPRT-deficient uncle. These findings show multiple
      derangement of nucleotide metabolism associated with partial HPRT deficiency. The
      enzyme alteration was presumably not the cause of neurological impairment since
      no neurological symptoms were found in the HPRT-deficient uncle, whereas they
      were present in the propositus' elder brother who had normal HPRT activity.

PMID- 12009424
TI  - Association of plasma phospholipid transfer protein activity with IDL and buoyant
      LDL: impact of gender and adiposity.
AB  - Current data suggest that phospholipid transfer protein (PLTP) has multiple
      metabolic functions, however, its physiological significance in humans remains to
      be clarified. To provide further insight into the role of PLTP in lipoprotein
      metabolism, plasma PLTP activity was measured, and lipoproteins were analyzed in
      134 non-diabetic individuals on a controlled diet. Insulin sensitivity index (Si)
      and body fat composition were also determined. Plasma PLTP activity was
      comparable between men (n=56) and women (n=78). However, in women but not in men,
      plasma PLTP activity was positively correlated with cholesterol, triglyceride,
      low density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B (r=0.38
      0.45, P< or =0.001), and with body mass index (BMI), subcutaneous and intra
      abdominal fat (SCF, IAF) (r=0.27-0.29, P<0.02). Among the different apo B
      containing lipoproteins (LpB) in women, PLTP was most highly correlated with
      intermediate density lipoproteins (IDL) and buoyant LDL (r=0.45-0.46, P<0.001).
      The correlation with IDL was significant only in women with BMI < or =27.5
      kg/m(2) (n=56). In men with BMI < or =27.5 kg/m(2) (n=35), PLTP activity was
      significantly correlated with buoyant LDL (r=0.40, P<0.02) and high density
      lipoprotein (HDL) (r=0.43, P<0.01). These data provide evidence for a role of
      PLTP in LpB metabolism, particularly IDL and buoyant LDL. They also suggest that
      gender and obesity-related factors can modulate the impact of PLTP on LpB.

PMID- 12009425
TI  - Novel ABCA1 compound variant associated with HDL cholesterol deficiency.
AB  - The recent discovery of an ATP-binding cassette transporter, ABCA1, as an
      important regulator of high density lipoprotein (HDL) metabolism and reverse
      cholesterol transport has facilitated the identification of novel variants
      associated with HDL cholesterol deficiency states. We identified a subject with
      HDL cholesterol deficiency (4 mg/dl) who developed and died of complications
      related to cerebral amyloid angiopathy (CAA). The proband had a compound
      heterozygous mutation. One mutation was a G3295T substitution with conversion of
      asparagine to tyrosine (D1099Y) in ABCA1. The single-base substitution at codon
      1099 resulted in the abolition of an RsaI cleavage site. The proband and affected
      individuals having another mutation were heterozygotes for T5966C with
      phenylalanine converted to serine (F2009S). The presence of the T5966C mutation
      was detected by restriction digestion with HinfI. These variants were not
      identified in over 400 chromosomes of healthy subjects. In the kindred, family
      members heterozygous for the ABCA1 variant exhibited low levels of HDL
      cholesterol. Direct sequencing of all coding regions and splice site junctions of
      other HDL candidate genes revealed no additional mutations, indicating that
      combined defective ABCA1 alleles may result in familial HDL deficiency.

PMID- 12009426
TI  - Rate of formation of AGEs during ascorbate glycation and during aging in human
      lens tissue.
AB  - The similarity of the yellow chromophores isolated from human cataracts with
      those from ascorbic acid modified calf lens proteins was recently published
      [Biochim. Biophys. Acta 1537 (2001) 14]. The data presented here additionally
      quantify age-dependent increases in individual yellow chromophores and
      fluorophores in the water-insoluble fraction of normal human lens. The water
      insoluble fraction of individual normal human lens was isolated, solubilized by
      sonication and digested with a battery of proteolytic enzymes under argon to
      prevent oxidation. The level of A(330)-absorbing yellow chromophores, 350/450 nm
      fluorophores and total water-insoluble (WI) protein were quantified in each lens.
      The total yellow chromophores and fluorophores accumulated in parallel with the
      increase in the water-insoluble protein fraction during aging. The digest from
      each single human lens was then subjected to Bio-Gel P-2 size-exclusion
      chromatography. The fractions obtained were further separated by a semi
      preparative prodigy C-18 high-performance liquid chromatography (RP-HPLC). Bio
      Gel P-2 chromatography showed four major fractions, each of which increased with
      age. RP-HPLC of the amino acid peak resolved five major A(330)-absorbing peaks
      and eight fluorescent peaks, and each peak increased coordinately with age. A
      late-eluting peak, which contained hydrophobic amino acids increased
      significantly after age 60. Aliquots from an in vitro glycation of calf lens
      proteins by ascorbic acid were removed and subjected to the same enzymatic
      digestion. Ascorbic acid-modified calf lens protein digests showed an almost
      identical profile of chromophores, which also increased in a time-dependent
      manner. The late-eluting peak, however, did not increase with the time of
      glycation and may not be an advanced glycation endproduct (AGE) product. The data
      indicate that the total water-insoluble proteins, individual yellow chromophores
      and fluorophores increased equally both with aging in normal human lens and
      during ascorbate glycation in vitro. The major protein modifications, which
      accumulate during aging, therefore, appear to be AGEs. Whereas the late-eluting
      peak, which showed poor correlation to ascorbylation, may represent UV filter
      compounds bound to lens proteins.

PMID- 12009427
TI  - Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect
      of regular exercise on the heart.
AB  - Many individuals with cardiac diseases undergo periodic physical conditioning
      with or without medication. Therefore, this study investigated the interaction of
      physical training and chronic nitric oxide synthase (NOS) inhibitor (nitro-L
      arginine methyl ester, L-NAME) treatment on blood pressure (BP), heart rate (HR)
      and cardiac oxidant/antioxidant systems in rats. Fisher 344 rats were divided
      into four groups and treated as follows: (1) sedentary control (SC), (2) exercise
      training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, s.c. for 8 weeks) and (4) ET+L
      NAME. BP and HR were monitored with tail-cuff method. The animals were sacrificed
      24 h after last treatments and hearts were isolated and analyzed. Physical
      conditioning significantly increased respiratory exchange ratio (RER), cardiac
      nitric oxide (NO) levels, NOS activity and endothelial (eNOS) and inducible
      (iNOS) protein expression. Training significantly enhanced cardiac glutathione
      (GSH) levels, GSH/GSSG ratio and up-regulation of cardiac copper/zinc-superoxide
      dismutase (CuZn-SOD), manganese (Mn)-SOD, catalase (CAT), glutathione peroxidase
      (GSH-Px) activity and protein expression. Training also caused depletion of
      cardiac malondialdehyde (MDA) and protein carbonyls. Chronic L-NAME
      administration resulted in depletion of cardiac NO level, NOS activity, eNOS,
      nNOS and iNOS protein expression, GSH/GSSG ratio and down-regulation of cardiac
      CuZn-SOD, Mn-SOD, CAT, GSH-PX, glutathione-S-transferase (GST) activity and
      protein expression. Chronic L-NAME administration enhanced cardiac xanthine
      oxidase (XO) activity, MDA levels and protein carbonyls. These biochemical
      changes were accompanied by increases in BP and HR after L-NAME administration.
      Interaction of training and NOS inhibitor treatment resulted in normalization of
      BP, HR and up-regulation of cardiac antioxidant defense system. The data suggest
      that physical conditioning attenuated the oxidative injury caused by chronic NOS
      inhibition by up-regulating the cardiac antioxidant defense system and lowering
      the BP and HR in rats.

PMID- 12009428
TI  - Beta-alanine protection against hypoxic liver injury in the rat.
AB  - Liver hypoxia still represents an important cause of liver injury during shock
      and liver transplantation. We have investigated the protective effects of beta
      alanine against hypoxic injury using isolated perfused rat livers and isolated
      rat hepatocyte suspensions. Perfusion with hypoxic Krebs-Henseleit buffer
      increased liver weight and caused a progressive release of lactate dehydrogenase
      (LDH) in the effluent perfusate. The addition of 5 mmol/l beta-alanine to the
      perfusion buffer completely prevented both weight increase and LDH leakage. These
      findings were confirmed by histological examinations showing that beta-alanine
      blocked the staining by trypan blue of either liver parenchymal and sinusoidal
      cells. Studies performed in isolated hepatocytes revealed that beta-alanine
      exerted its protective effects by interfering with Na+ accumulation induced by
      hypoxia. The addition of gamma-amino-butyric acid, which interfered with beta
      alanine uptake by the hepatocytes or of Na+/H+ ionophore monensin, reverted beta
      alanine protection in either hepatocyte suspensions or isolated perfused livers.
      We also observed that liver receiving beta-alanine were also protected against
      LDH leakage and weight increase caused by the perfusion with an hyposmotic (205
      mosm) hypoxic buffer obtained by decreasing NaCl content from 118 to 60 mmol/l.
      This latter effect was not reverted by blocking K+ efflux from hepatocyte with
      BaCl(2) (1mmol/l). Altogether these results indicated that beta-alanine protected
      against hypoxic liver injury by preventing Na+ overload and by increasing liver
      resistance to osmotic stress consequent to the impairment of ion homeostasis
      during hypoxia.

PMID- 12009429
TI  - Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase
      activity.
AB  - This study examines the effect of the antidepressants fluoxetine, sertraline and
      amitriptyline on cholinesterase (acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE)) activities in human serum and erythrocyte membrane
      (ghost). The concentrations used range from 3 to 60 microM for fluoxetine and
      amitriptyline and 0.3 to 12 microM for sertraline. At the micromolar range
      concentration, different classes of antidepressants, including fluoxetine and
      sertraline (selective serotonin reuptake inhibitors (SSRIs)) and amitriptyline
      (tricyclic antidepressant) inhibited human serum cholinesterase. The order of
      inhibitory potency was sertraline>amitriptyline>>fluoxetine and the IC(50) values
      were 4.05, 9.43 and 62 microM, respectively. Analysis of kinetic data indicated
      that the inhibition caused by all the antidepressants was mixed in nature. At the
      micromolar range concentration, sertraline (60-120 microM) and amitriptyline (60
      180 microM) inhibited human erythrocyte AChE. The order of inhibitory potency was
      sertraline>amitriptyline and the IC(50) values were 80 and 134 microM,
      respectively. Analysis of kinetic data indicated that the inhibition caused by
      all the antidepressants in AChE human erythrocyte membrane (ghost) was mixed in
      nature. The interaction of sertraline with the cholinesterase is labile since the
      removal of inhibitor by gel filtration recovered completely the enzyme activity.
      Our results demonstrate that the usual clinical antidepressants are inhibitors of
      the cholinesterases on human serum and erythrocyte membrane.

PMID- 12009430
TI  - Overexpression of kidney phosphatidylinositol 4-kinasebeta and phospholipase
      C(gamma1) proteins in two rodent models of polycystic kidney disease.
AB  - Our studies of renal phosphoinositide levels and metabolism in the pcy mouse with
      polycystic kidney disease (PKD) suggest that phosphatidylinositol kinase
      (PtdInsK) and phospholipase C (PLC) are elevated in this renal disorder.
      Therefore, the steady-state levels of select isoforms of these enzymes were
      examined in renal cytosolic and particulate (detergent-soluble) fractions in male
      and female normal and CD1-pcy/pcy (pcy) mice at 60, 120 and 180 days of age, and
      in male and female normal and diseased (Han:SPRD-cy) rats at 28 and 70 days of
      age. Disease-related increases in phosphatidylinositol 4-kinasebeta
      (PtdIns4Kbeta) and PLC(gamma1) levels were present in both models. PtdIns4Kbeta
      levels were higher by as much as 233% in pcy mice and by 95% in diseased Han:SPRD
      cy rats compared to normals of the same age and gender. Steady-state levels of
      PLC(gamma1) were as much as 74% and 35% higher in pcy mice and diseased Han:SPRD
      cy rats, respectively, compared to their controls. The consistency of these
      alterations in two accepted models of PKD indicates the importance of the
      phosphoinositide signalling pathway in the evolution of this disorder, and
      represents a potential site for therapeutic intervention.

PMID- 12009432
TI  - Effect of protein relaxation on electron transfer from the cytochrome subunit to
      the bacteriochlorophyll dimer in Rps. sulfoviridis reaction centers within mixed
      adiabatic/nonadiabatic model.
AB  - The broad set of nonexponential electron transfer (ET) kinetics in reaction
      centers (RC) from Rhodopseudomonas sulfoviridis in temperature range 297-40 K are
      described within a mixed adiabatic/nonadiabatic model. The key point of the model
      is the combination of Sumi-Marcus and Rips-Jortner approaches which can be
      represented by the separate contributions of temperature-independent vibrational
      (v) and temperature-dependent diffusive (d) coordinates to the preexponential
      factor, to the free energy of reaction DeltaG=DeltaG(v)+DeltaG(d)(T) and to the
      reorganization energy lambda=lambda(v)+lambda(d)(T). The broad distribution of
      protein dielectric relaxation times along the diffusive coordinate is considered
      within the Davidson-Cole formalism.

PMID- 12009433
TI  - Coupling of electron and proton transport in photosynthetic membranes: molecular
      mechanism.
AB  - Using the method of Modified Neglect of Diatomic Overlap (MNDO), the electronic
      structure of plastoquinol (PQH(2)) and plastoquinone (PQ) in neutral, singly (PQ(
      )) and doubly (PQ(2-)) reduced states is studied. The conformational analysis
      performed on these molecules shows that in the lowest energy conformation, the
      angle between the first link of the tail backbone and the ring plane of neutral
      and singly reduced PQ and plastoquinol is nearly the same and differs by 15
      degrees from that of doubly reduced PQ. Nevertheless, for all states of
      plastoquinone and for plastoquinol, the total energy changes by less than 0.2 eV
      when the studied angle is varied from 0 degrees to 180 degrees. As in Rhodobacter
      sphaeroides, the oxygen of the PQ ring is reported to form a hydrogen bond with a
      nitrogen in the ring of Histidine (His) L 190. The energy of the PQ-His complex
      was calculated for different redox states of PQ and for several values of the
      distance between the molecules (N-O distance from 0.2 to 0.5 nm). For every
      considered complexes, the total energy dependence on the proton position on the
      line connecting the N and O atoms was determined, to see if the hydrogen bond is
      formed. It is shown that for only singly reduced PQ this dependence has a
      symmetric two-well form, i.e. the hydrogen bond is formed. For neutral and doubly
      reduced PQ, the curve is also two-well but asymmetric, so that the proton is
      bound to His or to PQ, correspondingly. On the basis of these results, we propose
      the following scheme of electron-proton coupling. Negatively charged oxygens of
      PQ form H-bonds with proton donor groups of the surrounding protein and fix PQ in
      its pocket. While the negative charges of oxygens increase after quinone
      reduction, protons shift to PQ oxygens and form strong hydrogen bonds with them.
      Upon second PQ reduction, protons are torn away from surrounding amino acids and
      form covalent bonds with the quinol. Resulting PQH(2) detaches from its binding
      place and is replaced by a neutral PQ. The lacking protons on amino acids in the
      Q(B) pocket are replaced by a step-by-step transfer from the stroma bulk through
      the proton channels.

PMID- 12009434
TI  - Backward electron transport in photosystem 2 reaction center and temperature
      dependence of delayed luminescence characteristics.
AB  - The temperature dependence of parameters of light-induced changes in millisecond
      delayed luminescence (half-width of the maximum, maximal and steady-state
      luminescence intensity) is studied within the temperature range from -23 to 45
      degrees C in leaf segments of Chinese rose (Hibiscus rosa sinensis). Delayed
      luminescence (DL) is induced and registered by a homemade setup based on a Lewis
      Kasha-type phosphoroscope. The temperature dependence of steady-state
      luminescence intensity is shown to have two maxima, at -10 and 35 degrees C. At
      room temperatures, the steady-state value of luminescence intensity is minimal,
      and its value correlates with the temperature tolerance of the plant. Depending
      on cooling and heating regimes, the DL steady-state value vs. temperature curves
      is found to be different. We suppose this effect to be caused by temperature
      induced destructive changes in the structure of photosystem 2 reaction centre and
      probably by salting out.

PMID- 12009435
TI  - Enzyme-catalysed nitrate reduction-themes and variations as revealed by protein
      film voltammetry.
AB  - Protein film voltammetry has been used to define the catalytic performance of two
      nitrate reductases: the respiratory nitrate reductase, NarGH, from Paracoccus
      pantotrophus and the assimilatory nitrate reductase, NarB, from Synechococcus sp.
      PCC 7942. NarGH and NarB present distinct "fingerprints" of catalytic activity
      when viewed in this way. Potentials that provide insufficient driving force for
      significant rates of nitrate reduction by NarB result in appreciable rates of
      nitrate reduction by NarGH. However, both enzymes display complex modulations in
      their rate of substrate reduction when viewed across the electrochemical
      potential domain.

PMID- 12009436
TI  - Flavin photochemistry in the analysis of electron transfer reactions: role of
      charged and hydrophobic residues at the carboxyl terminus of ferredoxin-NADP(+)
      reductase in the interaction with its substrates.
AB  - The enzyme Ferredoxin-NADP(+) reductase participates in the reductive side of the
      photosynthetic chain transferring electrons from reduced Ferredoxin (Fd) (or
      Flavodoxin (Fld)) to NADP(+), a process that yields NADPH that can be used in
      many biosynthetic dark reactions. The involvement of specific amino acids in the
      interaction between the two proteins has been studied using site-directed
      mutagenesis. In the present study, the participation of charged (H299), polar
      (T302) or hydrophobic (V300) amino acid residues that are in the NADP(+)-binding
      domain of the reductase have been examined by analyzing its C-terminal region,
      which is located close to the active site. Stopped-flow and laser flash
      photolysis results of the reaction in which these mutant proteins participate
      show very little differences with respect to the wild-type protein. These results
      suggest that the NADPH-binding domain of the reductase has little effect on the
      processes of recognition and electron transfer to (and from) Fd or Fld, according
      to the recently reported crystallographic structure of the FNR/Fd complex.

PMID- 12009437
TI  - Indirect evidence of direct electron communication between the active site of
      galactose oxidase and a graphite electrode.
AB  - Bi-enzymatic biosensor based on galactose oxidase (GalOD) and horseradish
      peroxidase (HRP) using ferrocene as an efficient mediator was constructed. When a
      dependence of a working potential on the sensor performance was examined, an
      unusual behaviour was observed. With increasing of an applied working potential a
      lower concentration of substrate to attain full linear range was needed. A fully
      linear dependence from the first substrate addition was observed at and above the
      working potential of 150 mV. This activation of the biosensor response by an
      applied working potential very well corresponds with a formal potential of GalOD
      (156 mV). When a membrane prevented GalOD access to the electrode surface was
      applied, no activation effect of a working potential on the sensor performance
      was observed. Thus, it can be assumed that direct electron communication between
      GalOD and the electrode occurred.

PMID- 12009438
TI  - Monolayers of a de novo designed 4-alpha-helix bundle carboprotein and partial
      structures on Au(111)-surfaces.
AB  - Mapping of structure and function of proteins adsorbed on solid surfaces is
      important in many contexts. Electrochemical techniques based on single-crystal
      metal surfaces and in situ scanning probe microscopies (SPM) have recently opened
      new perspectives for mapping at the single-molecule level. De novo design of
      model proteins has evolved in parallel and holds promise for test and control of
      protein folding and for new tailored protein structural motifs. These two
      strategies are combined in the present report. We present a synthetic scheme for
      a new 4-alpha-helix bundle carboprotein built on a galactopyranoside derivative
      with a thiol anchor aglycon suitable for surface immobilization on gold. The
      galactopyranoside with thiol anchor and the thiol anchor alone were prepared for
      comparison. Voltammetry of the three molecules on Au(111) showed reductive
      desorption peaks caused by monolayer adsorption via thiolate-Au bonding. In situ
      STM of the thiol anchor disclosed an ordered adlayer with clear domains and
      molecular features. This holds promise, broadly for single-molecule voltammetry
      and the SPM and scanning tunnelling microscopy (STM) of natural and synthetic
      proteins.

PMID- 12009439
TI  - An impedance study of the adsorption of nucleic acid bases at glassy carbon
      electrodes.
AB  - Electrochemical impedance has been used to study the adsorption at glassy carbon
      electrodes of guanine, its corresponding nucleoside, guanosine, and adenine.
      Impedance studies at different concentrations and applied potentials show clearly
      that all three bases are adsorbed on the electrode, blocking the surface.
      Irradiating the electrode with low-frequency (20 kHz) ultrasound whilst recording
      the impedance spectra increased transport of molecules to the electrode surface
      with cavitation cleaning the surface and removing strongly adsorbed molecules of
      bases. In this way, sonoelectrochemical experiments enabled the electrode
      processes to be studied in the absence of adsorption.

PMID- 12009440
TI  - Electrochemical impedance spectroscopy of polynucleotide adsorption.
AB  - The dependence of the impedance of the electrode double layer of mercury
      electrode on frequency around the potentials of the tensammetric peaks of single
      stranded and double-helical polynucleotides and DNA was studied. From the
      frequency dependence of the impedance of the electrode double layer represented
      in a complex plane impedance plot, the electric equivalent circuit of the
      electrode covered with adsorbed DNA layer was determined. It was concluded that
      the desorption of denatured ssDNA is accompanied by higher dielectric losses than
      the desorption of native dsDNA. This can be explained by the higher flexibility
      of ssDNA compared to the dsDNA. The capacitance peak of single-stranded
      polyadenylic acid (poly A) observed at pH 8 around -1.3 V splits at low
      frequencies in two peaks.

PMID- 12009441
TI  - Two-dimensional condensation of nucleic acid components at mercury film and gold
      electrodes.
AB  - The adsorption of cytidine at the mercury film electrodes and at the Au (111)
      single crystal electrode has been investigated. Some kinetic aspects such as the
      influence of pH and temperature on the formation or dissolution of cytidine
      adlayer on the pyrolytic graphite electrode covered by a mercury film or on the
      Au (111) have been studied.

PMID- 12009442
TI  - A novel method of introducing hydrophobic moieties into oligonucleotides for
      covalent and non-covalent immobilization on electrode surfaces.
AB  - An effective method for the introduction of oleylamine-modified cytidine units
      into predetermined position(s) of the oligodeoxyribonucleotide (ON) chain during
      automated ON synthesis has been developed. The high yields of the condensation
      products upon the introduction of the modified units allow the methods suggested
      to be used for the synthesis of ONs with two hydrophobic substituents. We also
      suggest a simple method for obtaining ONs with 5'-terminal hydrophobic linker
      with free thiol group. The functionality of synthesized ON modified by thiol
      group and that with hydrophobic spacer for the detection DNA hybridization has
      been approved in conductometric experiments.

PMID- 12009443
TI  - Reduction of lapachones and their reaction with L-cysteine and mercaptoethanol on
      glassy carbon electrodes.
AB  - The electrochemical reduction of beta-lapachone and its 3-sulphonic salt was
      studied by cyclic, square wave and differential pulse voltammetry in aqueous
      media using a glassy carbon electrode. These compounds have a wide range of
      biological activities, including antibacterial, cytotoxic, antifungal,
      trypanocidal and anticancer action. The reduction of beta-lapachone in the
      presence of L-cysteine and 2-mercaptoethanol was studied and the results,
      together with others already published, suggest that the anticancer mechanism of
      beta-lapachones can be explained via interaction with topoisomerase.

PMID- 12009444
TI  - Catalytic signal of rabbit liver metallothionein on a mercury electrode: a
      combination of derivative chronopotentiometry with adsorptive transfer stripping.
AB  - Constant current chronopotentiometric stripping analysis (CPSA) in combination
      with adsorptive transfer stripping (AdTS) technique was used to study the rabbit
      liver metallothionein (MT) on a hanging mercury drop electrode (HMDE).
      Metallothionein yielded a distinct, sharp chronopotentiometric signal at very
      negative potentials (about -1.7 V), also known as the "peak H". The height and
      potential of this peak were dependent on experimental conditions, such as buffer
      composition, pH, and the presence oxygen in solutions. The peak H was highest in
      borate buffer with pH close to the isoelectric point (pI) of MT. The
      chronopotentiometric results contribute to a deeper understanding of the nature
      of catalytic hydrogen evolution and demonstrate the usefulness of the peak H in
      peptide and protein research.

PMID- 12009445
TI  - Differential pulse adsorptive stripping voltammetry of osmium-modified peptides.
AB  - Complexes of osmium tetroxide with nitrogen ligands were developed and used in
      our laboratory as probes of the DNA structure. Here, we show that the complex of
      osmium tetroxide with 2,2'-bipyridine (Os,bipy) can be used for modification and
      electrochemical detection of proteins at neutral pH. Salmon luteinizing hormone
      (SLH) containing two tryptophan (Trp) residues and human luteinizing hormone
      (HLH) containing one Trp were modified by Os,bipy and measured by differential
      pulse adsorptive stripping voltammetry (DPAdSV) at a hanging mercury drop
      electrode (HMDE). The intensity of the DPAdSV catalytic signals corresponded to
      the number of Trp residues in the peptide molecule. Decreasing pH of the
      background electrolyte from 6.6 to 3.8 led to the increase of DPAdSV signals,
      suggesting that at pH 3.8, the DPAdSV detection limit might be well below 1
      ng/ml. Our results suggest that Os,bipy is potentially useful for chemical
      modification of proteins.

PMID- 12009446
TI  - Mediator-modified electrodes for catalytic NADH oxidation: high rate constants at
      interesting overpotentials.
AB  - Carbon paste electrodes were modified with a nitrofluorenone derivative, 2,4,7
      trinitro-9-fluorenone, adsorbed on zirconium phosphate (ZP). After
      electrochemical reduction of the fluorenone derivative, it turns into a very
      efficient mediator for electrocatalytic NADH oxidation, with a formal potential
      of about +250 mV vs. Ag/AgCl. The electrochemistry and the electrocatalytic
      properties of the mediator were investigated with cyclic voltammetry and rotating
      disk electrode methodology. The second order rate constant with NADH was
      evaluated and found to be higher than 10(6) M(-1) s(-1), thus approaching true
      diffusion controlled currents for NADH oxidation.

PMID- 12009447
TI  - Nitric oxide determination by amperometric carbon fiber microelectrode.
AB  - Nitric oxide (NO) amperometric microsensor was prepared by the modification of
      bare carbon fiber electrode by Nafion and cellulose acetate (CA). Detection
      limit, response time, reproducibility and influence of some possible
      interferences (nitrite, nitrate, arginine) were tested and evaluated. This sensor
      was used for in vitro determination of NO release from fresh porcine aorta
      induced by calcium ionophore A23187 (CI).

PMID- 12009448
TI  - The role of hydrogenases in the anaerobic microbiologically influenced corrosion
      of steels.
AB  - The direct electron transfer between 316 L stainless steel and the NAD-dependent
      hydrogenase from Ralstonia eutropha was studied by spectroelectrochemistry. The
      presence of hydrogenase and NAD+ clearly increased the quantity of electricity,
      which was consumed during the electrolysis performed at potential lower than 
      0.70 V/SCE. The involvement of hydrogenase in the cathodic depolarisation theory
      was discussed in the light of these results.

PMID- 12009449
TI  - Electrochemical sensing of DNA-adriamycin interactions.
AB  - Adriamycin, a cancerostatic anthracycline antibiotic, causes considerable death
      of tumour cells, together with the induction of breaks in DNA single and double
      strands. The interaction of this compound with DNA was investigated using an
      electrochemical DNA-biosensor. Adriamycin intercalation in DNA disrupts the
      double helix and the detection of guanine and 8-oxoguanine could mimic one
      possible mechanism for the in vivo adriamycin drug action.

PMID- 12009450
TI  - New approaches in the development of DNA sensors: hybridization and
      electrochemical detection of DNA and RNA at two different surfaces.
AB  - Up to now, the development of the electrochemical DNA hybridization sensors
      relied on solid electrodes, on which both the hybridization and detection steps
      have been performed. Here we propose a new method in which the DNA hybridization
      is performed at commercially available magnetic beads and electrochemical
      detection on detection electrodes (DE). Due to minimum nonspecific DNA adsorption
      at the magnetic beads, very high specificity of the DNA hybridization is
      achieved. Optimum DE can be chosen only with respect to the given electrode
      process. It is shown that high sensitivity and specificity in the detection of
      relatively long target DNAs can be obtained (a) by using cathodic stripping
      voltammetry at mercury or solid mercury amalgam DEs for the determination of
      purine bases, released from DNA by acid treatment, and (b) by enzyme-linked
      immunoassay of target DNA modified by osmium tetroxide,2,2'-bipyridine (Os,bipy)
      at carbon DEs. Direct determination of Os,bipy at mercury and carbon electrodes
      is also possible.

PMID- 12009451
TI  - Surfactant bilayers for the direct electrochemical detection of affinity
      interactions.
AB  - Simple methods of preparing the direct affinity sensors are proposed. Due to the
      self-consistent introduction of a hydrocarbon chain bound with oligonucleotide
      pentadecathymidylate (dT(15)) into the hydrophobic region of surfactant bilayer
      or the adsorption of antibodies on the bilayer surface, the immobilizations of
      oligonucleotide or antibodies were carried out correspondingly. The responses
      were detected by impedance spectroscopy. Whereas the specific DNA-coupling caused
      the decrease of real part of impedance, the antibody-antigen interaction caused
      the increase of real part. The obtained results give an opportunity for the
      development of impedimetric affinity sensors for clinical analysis or for the
      detection of various environmental pollutants.

PMID- 12009452
TI  - A comparative thermodynamic study for both natural and artificial RNA/DNA-protein
      binary complexes.
AB  - In recent years, Systematic Evolution of Ligands by EXponential enrichment
      (SELEX) technique has been developed into a fast growing field. In contrast to
      traditional recognition elements, like antibody, our interests focus on novel
      molecular recognition elements based on nucleic acids, which are of value both
      for the therapy and biosensors. A comparative study of thermodynamic for both
      natural and artificial RNA/DNA-protein complexes would establish bases for a
      specificity of complex formation. In particular, we have shown that aptamers
      could be used for a direct measuring of thrombin enzymatic activity in a
      solution.

PMID- 12009453
TI  - A glucose/hydrogen peroxide biofuel cell that uses oxidase and peroxidase as
      catalysts by composite bulk-modified bioelectrodes based on a solid binding
      matrix.
AB  - An improved composite bulk-modified bioelectrode setup based on a solid binding
      matrix (SBM) has been used to develop a glucose/hydrogen peroxide biofuel cell.
      Fuel is combined through a catalytically promoted reaction with oxygen into and
      oxidized species and electricity. The present work explores the feasibility of a
      sugar-feed biofuel cell based on SBM technology. The biofuel cell that utilizes
      mediators as electron transporters from the glucose oxidation pathway of the
      enzyme directly to electrodes is considered in this work. The anode was a glucose
      oxidase (GOx, EC 1.1.3.4)/ferrocene-modified SBM/graphite composite electrode.
      The cathode was a horseradish peroxidase (HRP, EC 1.11.1.7)/ferrocene-modified
      SBM/graphite composite electrode. The composite transducer material was layered
      on a wide polymeric surface to obtain the biomodified electrodic elements, anodes
      and cathodes and were assembled into a biofuel cell using glucose and H(2)O(2) as
      the fuel substrate and the oxidizer. The electrochemical properties and the
      characteristics of single composite bioelectrodes are described. The open-circuit
      voltage of the cell was 0.22 V, and the power output of the cell was 0.15
      microW/cm(2) at 0.021 V. The biofuel cell proved to be stable for an extended
      period of continuous work (30 days). The reproducibility of the biotransducers
      fabrication was also investigated. In addition, an application of presented
      biofuel cell, e.g. the use of hydrolyzed corn syrup as renewable biofuels, was
      discussed.

PMID- 12009454
TI  - Electrochemical studies on reconstituted horseradish peroxidase modified carbon
      paste electrodes.
AB  - Horseradish peroxidase (HRP) is a heme protein that acts specifically on H(2)O(2)
      as the electron acceptor. Hemin (Ferriprotoporhyrin-IX) is the prosthetic group
      of the enzyme. A direct molecular wire to the redox center of the enzyme is
      expected to enhance the electrochemical response of the enzyme. Native HRP was
      immobilized onto the surface of glassy carbon (GC) matrix using a 16-atom spacer
      arm. We have also immobilized the redox center of the enzyme (hemin) through one
      of the propionate groups onto the surface of glassy carbon matrix using an 11
      atom spacer arm with amino terminus. Apoperoxidase was isolated according to the
      Teale's method and was allowed to reconstitute with the hemin-bound matrix for
      enzyme reconstitution. The HRP paste and reconstituted-HRP (rec-HRP) paste
      electrodes were used to study the electrochemical response to substrate H(2)O(2)
      using electrochemical techniques like cyclic voltammetry (CV) and flow injection
      (FI) studies. Flow injection studies using HRP paste electrode showed a linearity
      from 25 to 200 microM H(2)O(2). The rec-HRP paste showed approximately 100 times
      increase in the electron transfer rates compared to native HRP paste, and
      substrate linearity from 25 to 100 microM was observed.

PMID- 12009455
TI  - Amperometric urea biosensor based on urease and electropolymerized toluidine blue
      dye as a pH-sensitive redox probe.
AB  - The electropolymerized toluidine blue film deposited on the glassy carbon
      electrode show amperometrically detectable pH sensitivity. This feature of
      polytoluidine blue (PTOB) film was used for a construction of an amperometric
      urea biosensor. We have observed a linear shift of the formal redox potential
      with increasing pH value between 4 and 8 giving the slope of 81 mV(Delta) pH(-1).
      Polytoluidine blue film has had a significantly increased stability and higher
      electrochemical activity compared to the adsorbed monomeric dye. The
      polytoluidine blue urea biosensor has been operating at a working potential of 
      200 mV vs. SCE. The sensitivity of the biosensor was 980 nA mM(-1) cm(-2). The
      biosensor showed linearity in concentration range up to 0.8 mM with the detection
      limit of 0.02 mM (S/N=3).

PMID- 12009456
TI  - Modified electrodes for NADH oxidation and dehydrogenase-based biosensors.
AB  - The direct electrochemical oxidation of beta-nicotinamide adenine dinucleotide
      (NADH) at clean electrodes proceeds through a radical cation intermediate at high
      overpotentials and is subject to rapid fouling. Consequently, there has been a
      considerable body of work over the last 20 years looking at ways in which to
      catalyse the reaction using a wide variety of different types of modified
      electrode. These studies have resulted in a good knowledge of the essential
      features required for efficient catalysis. In designing modified electrodes for
      NADH oxidation, it is not only important to identify suitable redox groups, which
      can catalyse NADH oxidation and can be attached to the electrode surface; it is
      also important to ensure facile charge transport between the immobilised redox
      sites in order to ensure that, in multilayer systems, the whole of the redox film
      contributes to the catalytic oxidation. One way to achieve this is by the use of
      electronically conducting polymers such as poly(aniline).

PMID- 12009457
TI  - Affinity assembled multilayers for new dehydrogenase biosensors.
AB  - We propose a novel approach, which allows the control of the spatial arrangement
      of redox mediator, coenzyme and enzyme on the electrode at a molecular level,
      using essentially electrostatic interactions. The first step consists of
      adsorbing a monolayer of molecules out of a new family of redox mediators,
      substituted nitrofluorenones. In a second step, a monolayer of calcium cations is
      immobilized at the interface. It serves as a bridge between the redox mediator
      and the subsequently adsorbed coenzyme. The weak interaction between a carboxyl
      group of the redox mediator and the coenzyme's phosphate groups, revealed by QCM
      measurements, allows the coenzyme to keep its natural activity in the adsorbed
      state. In the last step, we use the intrinsic affinity of this monolayer of
      NAD(+) for dehydrogenases to build up a supramolecular sandwich composed of
      mediator/Ca(2+)/NAD(+)/dehydrogenase. This simple modification procedure, which
      might constitute a versatile approach for the low cost assembly of well-defined
      biosensors surfaces, has been successfully applied to the enzymatic detection of
      glucose, glutamate and alcohol.

PMID- 12009458
TI  - Monitoring of ethanol during fermentation using a microbial biosensor with
      enhanced selectivity.
AB  - The present study is concerning the construction of ferricyanide-mediated
      Gluconobacter oxydans cell ethanol biosensor. The size exclusion effect of a
      cellulose acetate membrane was used for elimination of glucose interferences
      during ethanol assays in real samples. A typical response time of the biosensor
      was 13 s with a high sensitivity of 3.5 microA mM(-1). The microbial biosensor
      exhibits a very low detection limit of 0.85 microM and a wide linear range from 2
      to 270 microM. The operational stability was excellent. During 8.5 h of
      repetitive ethanol assays, no decrease in the sensor sensitivity was observed.
      The biosensor was successfully used in the off-line monitoring of ethanol
      fermentation with a good agreement with HPLC measurements (R(2)=0.998).

PMID- 12009459
TI  - Impedimetric immunosensor using avidin-biotin for antibody immobilization.
AB  - The potentialities of an electrodeposited biotinylated polypyrrole film as an
      immobilisation matrix for the fabrication of impedimetric immunosensors are
      described. Biotinylated antibody (anti-human IgG), used as a model system, was
      attached to free biotin groups on the electrogenerated polypyrrole film using
      avidin as a coupling reagent. This immobilization method allows to obtain a
      highly reproducible and stable device. The resulting immunosensor has a linear
      dynamic range of 10-80 ng ml(-1) of antigen and a detection limit of 10 pg ml(
      1). Furthermore, this immunosensor exhibited minor loss in response after two
      regeneration steps.

PMID- 12009460
TI  - Mechanisms of the interaction of alpha-helical transmembrane peptides with
      phospholipid bilayers.
AB  - The synthetic peptide acetyl-K(2)-G-L(24)-K(2)-A-amide (P(24)) and its analogs
      have been successfully utilized as models of the hydrophobic transmembrane alpha
      helical segments of integral membrane proteins. The central polyleucine region of
      these peptides was designed to form a maximally stable, very hydrophobic alpha
      helix which will partition strongly into the hydrophobic environment of the lipid
      bilayer core, while the dilysine caps were designed to anchor the ends of these
      peptides to the polar surface of the lipid bilayer and to inhibit the lateral
      aggregation of these peptides. Moreover, the normally positively charged N
      terminus and the negatively charged C-terminus have both been blocked in order to
      provide a symmetrical tetracationic peptide, which will more faithfully mimic the
      transbilayer region of natural membrane proteins and preclude favorable
      electrostatic interactions. In fact, P(24) adopts a very stable alpha-helical
      conformation and transbilayer orientation in lipid model membranes. The results
      of our recent studies of the interaction of this family of alpha-helical
      transmembrane peptides with phospholipid bilayers are summarized here.

PMID- 12009461
TI  - Electric field effects in proteins in membranes.
AB  - Both the organization and function of protein nanostructures in membranes are
      related to the substructural properties of the lipid portion of the membrane.
      Potential differences that are established across the membrane and generate
      electric fields in these very thin portions are shown to modulate the
      organizational and functional properties of the protein modules. Many protein
      modules also have nonisotropic distributions of charged sites, including
      configurations in which there are regions containing predominantly positive fixed
      charges, juxtaposed with adjacent regions containing predominantly negative fixed
      charges. In these double fixed charge regions, very large electric fields can
      manifest in the ionic depletion layer at the junction of the two fixed charge
      regions. Consideration is also given to the manner in which the intense electric
      fields that are established in protein modules, such as proton ATPases, can
      modulate the chemical reactions that are associated with proton transport and
      dehydration reactions.

PMID- 12009462
TI  - Studying the spatial organization of membrane proteins by means of tritium
      stratigraphy: bacteriorhodopsin in purple membrane.
AB  - The topography of bacteriorhodopsin (bR) in situ was earlier studied by using the
      tritium bombardment approach [Eur. J. Biochem. 178 (1988) 123]. Now, having the X
      ray crystallography data of bR at atom resolution [Proc. Natl. Acad. Sci. 95
      (1998) 11673], we estimated the influence of membrane environment (lipid and
      protein) on tritium incorporation into amino acid residues forming transmembrane
      helices. We have determined the tritium flux attenuation coefficients for
      residues 10-29 of helix A. They turned out to be low (0.04+/-0.02 A(-1)) for
      residues adjacent to the lipid matrix, and almost fourfold higher (0.15+/-0.05 A(
      1)) for those oriented to the neighboring transmembrane helices. We believe that
      tritium incorporation data could help modeling transmembrane segment arrangement
      in the membrane.

PMID- 12009463
TI  - DC photoelectric signals from bacteriorhodopsin adsorbed on lipid monolayers and
      thiol/lipid bilayers supported by mercury.
AB  - Purple membrane (PM) fragments were adsorbed on a dioleoylphosphatidylcholine
      (DOPC) monolayer and on a mixed alkanethiol/DOPC bilayer supported by mercury to
      investigate the kinetics of light-driven proton transport by bacteriorhodopsin
      (bR). The light-on and light-off capacitive currents on an alkanethiol/DOPC
      bilayer at pH 6.4 were interpreted on the basis of a simple equivalent circuit.
      The pH dependence of the biphasic decay kinetics of the light-on currents was
      analyzed to estimate the pK(a) values for the transitions releasing protons to,
      and taking up protons from, the solution. The linear dependence of the stationary
      light-on current of bR on a DOPC monolayer self-assembled on mercury upon the
      applied potential was interpreted on the basis of an equivalent circuit.

PMID- 12009464
TI  - Mixed urease/amphiphile LB films and their application for biosensor development.
AB  - The optimal conditions for the formation of a stable mixed urease/octadecylamine
      (ODA) film at the air-water interface are determined. This film is efficiently
      transferred onto the hydrophobized surface of a pH-ISFET, and the features of the
      urea enzymatic field-effect transistor (ENFET) are determined: detection limit
      0.2 mM, response time 15 s, and dynamic range 0-20 mM.

PMID- 12009465
TI  - Monolayers and multilayers of chlorophyll [correction of chlorophyl] a on a
      mercury electrode.
AB  - A novel experimental technique used to investigate chlorophyll films on a hanging
      mercury drop electrode is described. Two different procedures are employed to
      prepare self-assembled chlorophyll monolayers and multilayers on the mercury
      electrode. Upon illuminating the chlorophyll a (Chl)-coated mercury electrode
      with an appropriate light source, the photocurrents generated by the Chl
      aggregates are measured under short-circuit conditions in the absence of
      photoartefacts. The preliminary results obtained by this novel technique are
      presented.

PMID- 12009466
TI  - Ionic conductivity of electroporated lipid bilayer membranes.
AB  - The ionic conductivity of lipid membrane pores has been theoretically analysed in
      terms of electrostatic interactions of the transported ions with the low
      dielectric pore wall for a commonly encountered case of unequal concentrations of
      electrolyte on the two sides of curved lipid membranes. Theoretical analysis of
      the data on the conductivity of the electroporated membrane of lipid vesicles
      (Lecithin 20%) of radius a=90 nm yields the molar energy of interaction of a
      small monovalent ion with a pore wall w(0)=9+/-1 RT (or w(0)=22+/-kJ mol(-1)),
      corresponding to a mean pore radius of (-)r(p)=0.56+/-0.05 nm. The proposed
      theoretical approach provides a tool for the analysis and description of the
      nonlinear current-voltage dependencies in membrane pores and channels.

PMID- 12009467
TI  - Spatial distribution of ion channel activity in biological membranes: the role of
      noise.
AB  - A new approach is proposed to model a collective ion channel dynamics. We have
      assumed that ion channels create a two-component spatio-temporal interaction
      field. Every channel at its current spatial location in membrane contributes
      permanently to this field with its state (open or closed) and coupling strength
      to other channels. This field is described by a reaction-diffusion equation, the
      transition of ion channel from closed to open state (and vice versa) is described
      by a master equation, and migration of channels in membrane is described by a set
      of Langevin equations coupled by the interaction field. Within this model, we
      have investigated critical conditions for spatial distribution of ion channel
      activity.

PMID- 12009468
TI  - The 40th anniversary of bilayer lipid membrane research.
AB  - This paper presents a historic perspective on the origin of the lipid bilayer
      concept and its experimental realization. Additionally, current studies in close
      collaboration with our colleagues on the use of supported BLMs as biosensors and
      molecular devices are delineated. Further, recent research of others on BLMs
      (planar lipid bilayers) is referenced.

PMID- 12009469
TI  - Polyelectrolyte-supported lipid membranes.
AB  - In this work, we report the influence of the electrostatic interaction between
      lipid bilayer membranes and their solid polyelectrolyte multilayer support on the
      properties of the membrane. All involved sample preparation steps were carried
      out as convenient adsorption procedures from aqueous solutions. The lipid
      fluidity within the membrane as well as the surface coverage of the support could
      be tailored via the electrostatic interaction strength between the lipid bilayer
      and the supporting polyelectrolyte cushion.

PMID- 12009470
TI  - Electrochemical studies of blocking properties of solid supported tethered lipid
      membranes on gold.
AB  - The insulating properties of self-assembled thiolipid monolayers and tethered
      lipid bilayers on polycrystalline gold electrodes were studied by means of cyclic
      voltammetry (CV). These films were formed by two-step self-assembly processes.
      Electrochemical measurements of the heterogeneous electron transfer rate constant
      of different redox couples such as potassium ferrocyanide (K(4)[Fe(CN)(6)]) and
      dopamine (DP) were used to examine the molecular integrity and structural defects
      and pinholes within the monolayers. We demonstrate by means of cyclic voltammetry
      that the bilayer lipid membranes tethered to the gold surface are blocking,
      stable, yet retaining their dynamic properties and can be used as a model of the
      cell membrane.

PMID- 12009471
TI  - Cyclic voltammetry study of glucose and insulin interactions with supported lipid
      membrane.
AB  - The effect of D-glucose and insulin on conducting properties of supported bilayer
      lipid membranes (s-BLM) modified by anthraquinone-2-sulphonic acid (AQS) at the
      presence of potassium ferricyanide was studied by means of cyclic voltammetry
      (CV). Both the oxidation and the reduction current peaks were found to decrease
      at the presence of glucose in concentration range varying from 10 to 320 mM. The
      influence of insulin on membrane properties is ambiguous. While the pretreatment
      of membrane with 20 mU l(-1) of insulin evoked slight increase of the current
      with unchanged course of the dependence of peak current on glucose, the decrease
      of conductance was observed above 10(5) mU l(-1) of insulin.

PMID- 12009472
TI  - DNA-membrane complexes, mitochondria and aging.
AB  - The results of extensive in vitro studies of DNA-lipid complexes allowed us to
      propose a model for the structure of such complexes and their involvement in the
      formation of DNA-membrane complexes (DMC). DMC seem to form the basis for such
      cellular structures as Bayer's junctions and nucleoid of bacteria, the nuclear
      pores, annulate lamellae and nucleoid of eucaryotes. The role of DMC in gene
      expression is discussed.Numerical density of mitochondria during cell aging
      correlates with the density of bacteria in batch culture. It is concluded that
      aging is caused by the unlimited growth of mitochondria and their subsequent
      degradation. The role of DMC in mitochondrial DNA damage at aging is discussed.
      The way of increasing the life span by controlling the density of mitochondria in
      a cell volume is likewise discussed. DMC formed between any two intracellular
      membranes can serve the basis for the membrane continuum in a cell.

PMID- 12009473
TI  - Specific natural DNA-bound lipids in post-genome era. The lipid conception of
      chromatin organization.
AB  - Two pools of DNA-bound lipids were isolated from DNA supramolecular complex (SC
      DNA): loosely bound (extracted with 35% ethanol) and tightly bound lipids
      (extracted after additional treatment DNase I). The compositions of the two lipid
      pools from different sources (rat thymus, liver, loach sperm, pigeon
      erythrocytes, Zajdel ascites hepatoma, Ehrlich ascites carcinoma, sarcoma 37,
      Escherichia coli B and T2 phage) were studied. The possible functions of DNA
      bound lipids, especially of cardiolipin and cholesterol, at the attachment of DNA
      loops to the nuclear matrix, in DNA replicon organization, replication and
      transcription are discussed.

PMID- 12009474
TI  - The asymmetric, rectifier-like I-V curve of the Na/K pump transient currents in
      frog skeletal muscle fibers.
AB  - The Na/K pump transient currents in skeletal muscle fiber were identified using
      an improved double Vaseline gap voltage clamp technique. The asymmetric
      characteristics of the pump current-voltage relationship were studied. The
      definition of the Na/K pump currents was the ouabain-sensitive currents, where
      ouabain is a specific Na/K ATPase inhibitor. Membrane potential was held at -90
      mV, the membrane resting potential. A series of stimulation pulse-pairs symmetric
      to the membrane resting potential were applied to the cell membrane. The
      summation of the currents responding to the two pulses in each pair indicates the
      asymmetry of the pump currents with respect to the membrane resting potential.The
      voltage dependence of the Na/K pump transient currents from skeletal muscle is
      similar to the steady-state I-V curve from either skeletal muscle fibers or
      cardiac muscles. It is a sigmoidal-shaped, asymmetric curve with respect to the
      membrane resting potential. This asymmetric, rectifier-like voltage dependence
      indicates that a symmetric oscillating membrane potential may generate a net,
      outward pump current. In other words, the Na/K pump molecules may be activated by
      an oscillating membrane potential.

PMID- 12009475
TI  - The influence of sugar synthesis and transport rates on bioenergetics and
      kinetics of higher plant photosynthesis.
AB  - We have obtained the theoretical dependences of stromal metabolite steady-state
      concentrations on external inorganic phosphate (P(i)) concentration. For this
      purpose, the theoretical model of photosynthesis, earlier described in [Ann.
      Appl. Biol. 138 (2001) 117], was modified to account for the regulation of starch
      formation by 3-phosphoglycerate (PGA) to P(i) ratio. When the rate constant of
      starch synthesis is taken to be independent on PGA/P(i) ratio, the steady-state
      concentrations of Calvin cycle metabolites and starch were found to change
      insignificantly as external P(i) concentration increases in wide range. However,
      as external P(i) range exceeds a critical value, the steady-state concentrations
      of all metabolites change abruptly. If the rate constant of starch synthesis
      depends on PGA/P(i) ratio, the steady-state concentrations of stromal metabolites
      change qualitatively in the same way with the increase of external P(i). However,
      no abrupt changes of metabolite and starch steady-state levels at high
      concentration of P(i) are observed. These results testify that the control of
      starch synthesis by PGA/P(i) ratio makes the photosynthetic system more stable in
      wide range of external P(i) concentrations.

PMID- 12009476
TI  - Understanding conditions for which biological effects of nonionizing
      electromagnetic fields can be expected.
AB  - Scientific interest in the interaction of nonionizing electromagnetic fields with
      biological systems is longstanding, but often still controversial. Theories,
      models and computer simulations have usually emphasized physical interactions
      with subsystems (e.g. cell membranes) of a biological system. By extending this
      first necessary physical step to a second step of explicitly and quantitatively
      considering chemical changes, increased understanding appears possible. In the
      case of "strong fields", the role of field-altered chemistry is important to
      electrochemotherapy [Biochem. Pharmacol. 42, Suppl. (1991) 567] and creation of
      transdermal microconduits [Bioelectrochem. Bioenerg. 49 (1999) 11; J. Controlled
      Release 61 (1999) 185; J. Invest. Dermatol. 116 (2001) 40] For "weak fields" (a
      topic with much more controversy) consideration of chemical change shows that
      organized multicellular systems can be understood to respond to extremely small
      electric [Chaos 8 (1998) 576] or magnetic fields [Nature 405 (2000) 707]. In
      contrast, isolated individual cells interacting via voltage-gated channels [Proc.
      Natl. Acad. Sci. 92 (1995) 3740; Biophys. J. 75 (1998) 2251; Bioelectromagnetics
      20 (1999) 102], or processes without "temperature compensation" [Biophys. J. 76
      (1999) 3026], appear implausible. Satisfactory understanding is likely only if
      experimental and theoretical work is reconciled, which should therefore be
      emphasized. The interaction of electromagnetic fields with biological systems is
      of interest because of fundamental scientific curiosity, potential medical
      benefits and possible human health hazards.

PMID- 12009477
TI  - Estimating the subcellular absorption of electric field energy: equations for an
      ellipsoidal single shell model.
AB  - An oriented single shell model is used to describe the absorption of electric
      field energy for a cell of the general ellipsoidal shape exposed to a homogeneous
      AC-field. A finite element approach allowed us to derive characteristic equations
      describing the dependence of the field distribution on the cell geometry, the
      electric properties of the structural media, membrane and bulk solutions, as well
      as on the field frequency with a subcellular resolution. Finally, equations were
      derived for the absorption at certain sites of the model. The model allows for
      the introduction of frequency-dependent cellular media properties.
      Experimentally, the new cell parameters can be verified by dielectric single-cell
      spectroscopy.

PMID- 12009478
TI  - Cellular absorption of electric field energy: influence of molecular properties
      of the cytoplasm.
AB  - Molecular dispersions may significantly alter the frequency dependence of
      structural polarizations. Consequently, the molecular properties cannot be
      neglected when the energy absorption is calculated with a subcellular resolution.
      Our example presents calculations that explain the absorption in single human red
      blood cells. The molecular properties of the cytoplasm have been derived from
      literature data on the impedance of Hb suspensions. The resulting cell properties
      were then compared to own data obtained by single cell dielectric spectroscopy.

PMID- 12009479
TI  - Evaluation of viability of retinal photoreceptor cells by using their endogenous
      electrical field.
AB  - The rod photoreceptor cells are electrical dipoles sustained by cell metabolic
      energy. Polarity of photoreceptor cells is directly connected to the so-called
      "dark current" which circulate along the living photoreceptors. Since only the
      living cells in a good functional state display electrical polarity, the
      orientation of photoreceptors in static electric field reflects their viability
      as long as it depends on the functionality of molecular mechanisms that maintain
      the dark current. Studying the rod cells' orientation in static electric field at
      different times after their isolation is thus an accurate way to evaluate the
      cell viability/degeneration. Retinal transplant experiments in animals and
      humans, which are presently in progress, require a quick and reliable viability
      test of cells/tissue to be transplanted. Checking the orientation pattern of rod
      photoreceptors in static electric field prior to transplantation is a candidate
      method for an accurate cell viability test.

PMID- 12009480
TI  - The effects of low level microwaves on the fluidity of photoreceptor cell
      membrane.
AB  - Due to the extensive use of electromagnetic fields in everyday life, more
      information is required for the detection of mechanisms of interaction and the
      possible side effects of electromagnetic radiation on the structure and function
      of the organism. In this paper, we study the effects of low-power microwaves
      (2.45 GHz) on the membrane fluidity of rod photoreceptor cells. The retina is
      expected to be very sensitive to microwave irradiation due to the polar character
      of the photoreceptor cells [Biochim. Biophys. Acta 1273 (1995) 217] as well as to
      its high water content [Stud. Biophys. 81 (1981) 39].

PMID- 12009481
TI  - Effects of static magnetic field on human leukemic cell line HL-60.
AB  - A number of structures with magnetic moments exists in living organisms that may
      be oriented by magnetic field. While most experimental efforts belong to the area
      of effects induced by weak and extremely low-frequency electromagnetic fields, we
      attempt to give an attention to the biological effects of strong static magnetic
      fields. The influence of static magnetic field (SMF) on metabolic activity of
      cells was examined. The metabolic activity retardation is observed in human
      leukemic cell line HL-60 exposed to 1-T SMF for 72 h. The retardation effect was
      observed as well as in the presence of the mixture of the antineoplastic drugs 5
      fluorouracil, cisplatin, doxorubicin and vincristine.

PMID- 12009482
TI  - Clinical evaluation of safety and human tolerance of electrical sensation induced
      by electric fields with non-invasive electrodes.
AB  - This paper reports the first clinical safety study of human tolerance of
      electrical sensation using non-invasive, flexible surface-type electrodes and
      exponentially decaying electric pulses. The study evaluated the effect of
      electric fields in the absence of a drug and an anesthetic, and was performed in
      light of potential applications in the field of erectile dysfunction (ED). Twenty
      impotent patients who had previously received injection or intraurethral
      therapies were enrolled in the study. Voltage escalations from 50 to 80 V (in 10
      V increments) with a single pulse of 3-ms duration were performed with meander
      type electrodes placed on the shaft and part of the glans of the penis. The
      electric fields-induced sensation was assessed via a pain scale from 0 to 10. All
      20 patients, who were free to withdraw from the study at any point, completed the
      voltage escalation study. No clinical safety concerns were apparent and no skin
      irritation was observed after electric treatment. Our initial study indicates
      that the pulses in the tested voltage range were well tolerated by most patients.
      In previous animal experiments under analogous experimental conditions, the
      application of 50 V has been found effective for transdermal drug delivery into
      the penis.

PMID- 12009483
TI  - Festschrift in honour of Peter Fried.

PMID- 12009484
TI  - Cocaine exposure and developmental outcome from birth to 6 months.
AB  - The theoretical framework for many of the early studies of prenatal cocaine
      exposure has been rooted in the basic concepts of teratology/developmental
      toxicology. Few have published longitudinal analyses of the complex interplay
      between the relative effects of prenatal cocaine exposure and perinatal and
      environmental factors on development. The purpose of this paper was to use
      structural equation modeling to describe the direct and indirect effects of
      prenatal drug exposure on developmental outcome from birth to age 6 months. Key
      variables considered for study include prenatal drug exposure, perinatal medical
      characteristics, maternal/caregiver/family characteristics, the home environment,
      and neurobehavioral outcomes. We prospectively enrolled 154 predominantly crack
      using women. A priori exclusion criteria included: <18 years old, major illnesses
      diagnosed prior to pregnancy, chronic use of legal drugs, and any use of illicit
      drugs other than cocaine and marijuana. From the pool of noncocaine users, 154
      subjects were matched to users on pregnancy risk, parity, race, and socioeconomic
      status. At the end of each trimester, experienced staff conducted private
      interviews prompting memory of amount and timing of past drug use. Urine
      specimens were collected at two unanticipated times; positive screens were
      confirmed by gas chromatography/mass spectroscopy. Measures analyzed include
      medical (birth) and developmental (birth, 1 month, 6 months) assessments, all
      performed by blinded evaluators, as well as caregiver characteristics and
      environmental factors (birth, 1 month). A series of four theoretical models was
      tested, one for each time point (birth, 1 month, 6 months) and a longitudinal
      model spanning birth to 6 months. Key findings include direct effects of prenatal
      cocaine exposure on development at birth in the birth model and on development at
      birth and 6 months in the longitudinal model. In addition, indirect effects of
      prenatal cocaine exposure were identified on development at birth, 1 month, and 6
      months, mediated through the prenatal use of alcohol and tobacco and the birth
      head circumference. Implications of these and other findings, including the
      advantages and limitations of structural equation modeling, are discussed.

PMID- 12009485
TI  - Longitudinal influence of prenatal cocaine exposure on child language
      functioning.
AB  - The present study estimates the longitudinal effects of in utero cocaine exposure
      on language functioning at 3, 5 and 7 years of age in an urban sample of 443 full
      term children (236 cocaine-exposed and 207 noncocaine-exposed) participating in
      the Miami Prenatal Cocaine Study. The sample was enrolled prospectively at birth,
      with documentation of prenatal drug exposure status through maternal interview
      and urine and meconium toxicology assays. Language functioning was measured at
      ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals
      Preschool (CELF-P) and at age 7 years using the Core Language Domain of the
      NEPSY: A Developmental Neuropsychological Assessment. Longitudinal Generalized
      Linear Model and Generalized Estimating Equations (GLM/GEE) analyses revealed an
      association between prenatal cocaine exposure and deficits in total language
      functioning after statistically controlling for child sex, visit age, prenatal
      exposure to alcohol, marijuana and tobacco and over 20 additional medical and
      sociodemographic covariates drawn from potentially confounding influences
      assessed at birth and follow-up visits (D=-0.17; 95% CI=-0.32, -0.03; P=.019).
      The link from prenatal cocaine exposure to later language deficits does not
      appear to be mediated by cocaine-associated deficits in birth weight, length or
      head circumference. Overall, the evidence tends to support an inference of a
      stable cocaine-specific effect on indicators of language functioning during early
      childhood through age 7 years.

PMID- 12009486
TI  - Prenatal alcohol and marijuana exposure: effects on neuropsychological outcomes
      at 10 years.
AB  - This report from a longitudinal study of the effects of prenatal alcohol and
      marijuana exposure investigates whether these drugs affect neuropsychological
      development at 10 years of age. Women were recruited from a medical assistance
      prenatal clinic and interviewed about their substance use at the end of each
      trimester of pregnancy, at 8 and 18 months, and at 3, 6, 10, 14, and 16 years.
      Half of the women were African American, and half were Caucasian. The women were
      generally from lower socioeconomic status families and had obtained high school
      degrees. At the 10-year follow-up, 593 children completed a neuropsychological
      battery, which focused on problem solving, learning and memory, mental
      flexibility, psychomotor speed, attention, and impulsivity. Prenatal alcohol use
      was found to have a significant negative impact on learning and memory skills, as
      measured by the WRAML. Prenatal marijuana exposure also had an effect on learning
      and memory, as well as on impulsivity, as measured by a continuous performance
      task. The effects of prenatal alcohol and marijuana exposure persisted when other
      predictors of learning and memory were controlled. We continue to follow these
      offspring into the adolescent years when further neuropsychological deficits may
      become evident.

PMID- 12009487
TI  - Cocaine and development: a retrospective perspective.
AB  - Neurobehavioral alterations evident in offspring of Sprague-Dawley rat dams
      exposed to 40 mg/kg/day cocaine subcutaneously from gestational days 8-20 are
      reviewed. Consequences for offspring are often age dependent: for instance,
      reliable deficits in classical conditioning are evident during the early
      postnatal period, whereas cognitive effects are less pervasive in adulthood,
      although apparent in tasks such as reversal training. Gender of offspring is
      another variable of importance, particularly when testing animals in adulthood,
      with adult male offspring being more likely than their female counterparts to
      exhibit alterations following the prenatal exposure regimen. Characteristics of
      the test situation likewise influence detection of outcome effects, with effects
      particularly likely to emerge under stressful testing conditions or other
      challenges to the organism. Under these circumstances, alterations in
      responsiveness to stressors also sometimes emerged in offspring of pair-fed (PF)
      dams (whose food intake was restricted to match that of cocaine-exposed [COC]
      dams); these findings perhaps should not be surprising given that pair feeding is
      a stressor and prenatal stress is known to alter later stressor responsiveness.
      Although several approaches to equate food intake or avoid pair feeding have
      yielded disappointing findings, one promising approach is to initiate cocaine
      administration prior to mating followed by exposure throughout gestation.
      Premating exposure to cocaine was sufficient to eliminate anorexic effects of
      drug delivery during pregnancy, although it remains to be seen how similar the
      pattern of neurobehavioral alterations that emerge with this extended exposure
      regimen will be to effects seen following more restricted gestational exposure.

PMID- 12009488
TI  - Studies of prenatal exposure to drugs: focusing on parental care of children.
AB  - A considerable body of research suggests that children who are prenatally exposed
      to alcohol and other drugs are also at risk for receiving poor quality parental
      care. Previous research in human behavioral teratology has focused on postnatal
      environment as a potential confounding factor. Yet, developmental theory suggests
      that development proceeds as a series of transactions between children's
      characteristics and their environments. In order that possible teratologic
      effects not be underestimated, future work needs to give more consideration to
      ways in which parental care may be influenced by child behavior and to ways in
      which postnatal environment might moderate the expression of teratologic effects.
      Studies must focus on the role of prenatal drug exposure within a broader system
      of variables that includes factors present in children's environments over time.

PMID- 12009489
TI  - Forgotten fathers: an exploratory study of mothers' report of drug and alcohol
      problems among fathers of urban newborns.
AB  - OBJECTIVES: To investigate the relationship between fathers' substance use and
      maternal and paternal background characteristics, infant outcome measures, and
      fathers' frequency of caregiving at 6 months postpartum in a cohort of cocaine
      exposed and unexposed infants. METHODS: Secondary analysis was completed on data
      collected through interviews and medical records obtained from 252 mothers
      participating in an ongoing longitudinal study of cocaine-exposed and unexposed
      mothers and infants. RESULTS: By maternal report, 22% of the mothers reported
      that the father of the baby had a history of a drug and/or alcohol problem.
      Mothers who were classified as heavier cocaine users were 1.6 times more likely
      than lighter cocaine users and 2.6 times more likely than nonusers to report that
      the father of the baby had a history of a drug and/or alcohol problem. There was
      a significant relationship between the father's reported history of a drug and/or
      alcohol problem and the mother's history of mental and physical abuse during
      pregnancy; P=.03, P=.001, respectively). Fathers with a history of a drug and/or
      alcohol problem were more likely to have been in jail (P=.001) and to be
      unemployed at the time of delivery (P=.04) than fathers without a history of a
      drug and/or alcohol problem. On bivariate analysis, newborns of fathers with a
      history by mother's report of a drug or alcohol problem had significantly lower
      mean birthweights (3003 vs. 3213 g, P=.005) and lengths (47.5 vs. 48.6 cm, P=.01)
      than newborns of fathers with no such history. However after control for mothers'
      prenatal use of cocaine, marijuana, cigarettes, and alcohol and for infant gender
      and gestational age, the differences were not statistically significant (P=.15
      for both measurements). Head circumference did not differ significantly between
      groups in either bivariate or multivariate analyses. Fathers with a reported
      history of drug and/or alcohol problems were more likely to care for the baby at
      least once a week than fathers without such a history of a drug and/or alcohol
      problem at 6 months postpartum. CONCLUSIONS: Childhood cognitive and behavioral
      outcomes currently attributed to maternal substance abuse may also reflect the
      genetic, teratogenic, and social influence of fathers. Within an urban, at-risk
      population, it is important to inquire about the father's participation in the
      day-to-day life of the infant and to address the father's as well as the mother's
      possible need for substance abuse treatment and support in parenting.

PMID- 12009490
TI  - Breast-feeding and gender as moderators of teratogenic effects on cognitive
      development.
AB  - Researchers in the Netherlands have reported that the associations of prenatal
      polychlorinated biphenyl (PCB) exposure with poorer cognitive performance in
      childhood are generally stronger and statistically significant only among non
      breast-fed children. This paper reports a similar pattern of greater
      vulnerability among non-breast-fed children in the Michigan cohort of children
      whose mothers had eaten PCB-contaminated Lake Michigan fish. It is difficult to
      determine from prospective human longitudinal data whether the apparent decreased
      vulnerability among breast-fed children is due to nutrients in breast milk that
      might attenuate the adverse neurochemical effects of this exposure and/or the
      more optimal intellectual stimulation that was provided by the breast-feeding
      mothers in these cohorts. The latter interpretation was supported by analyses
      demonstrating that virtually all of the positive associations between breast
      feeding and cognitive outcome can be accounted for statistically by measures of
      quality of parental intellectual input and that the adverse effects associated
      with prenatal PCB exposure were also markedly stronger in children raised by less
      verbally competent mothers, who presumably provided less optimal intellectual
      stimulation. Because there were no consistent patterns of differential
      vulnerability for either gender, these data did not support the hypothesis that
      prenatal PCB exposure may disrupt cognitive development due to the estrogenic or
      antiestrogenic properties of its congeners and metabolites.

PMID- 12009491
TI  - Interaction of maternal smoking and other in-pregnancy exposures: analytic
      considerations.
AB  - The teratogenicity of cigarette smoke has been widely researched over the past
      two decades, in large part due to the work of Fried et al. The current study was
      designed to investigate some methodological issues surrounding the investigation
      of the effects of maternal smoking along with other potentially teratogenic
      agents in pregnancy. Specifically, maternal smoking was investigated both as a
      covariate and with regards to its main and interactive effects on child IQ in a
      prospectively ascertained sample of children whose mothers reported pregnancy
      exposures to four classes of agents: varicella virus infection (VC), selective
      serotonin reuptake inhibitors (SSRIs), antiepileptic drugs (AEDs) and
      benzodiazepines (BZDs). Children were also included whose mothers were not
      exposed to one of these four agents during pregnancy. The goal of this study was
      not to examine the behavioral teratogenic potential of these agents or of
      maternal smoking. Rather, our goal was to illustrate some methodological issues
      in addressing the combined effects of these agents in behavioral teratology. In
      the analyses of all four exposures, when smoking was considered as a covariate,
      it was either a significant or marginally significant covariate and the exposure
      of interest was not significantly related to a change in IQ score. However, when
      maternal smoking was considered as a factor in the analyses, four different
      patterns emerged illustrating the potential importance of properly addressing
      maternal smoking in the analysis of other potential behavioral teratogens.

PMID- 12009492
TI  - Nicotine and the adolescent brain: insights from an animal model.
AB  - Tobacco use in adolescence represents one of the major challenges to the future
      of public health. Whereas numerous studies have explored the consequences of
      fetal or adult nicotine effects, little or no basic research has been conducted
      for nicotine during adolescence, the stage at which regular cigarette use
      typically begins. This review describes the recent development of a model of
      adolescent nicotine administration in rats that recapitulates the plasma levels
      of nicotine found in smokers. Adolescent nicotine evoked CNS nicotinic receptor
      up-regulation with a distinctly different regional pattern from that seen in the
      adult; increased receptor expression in male rats persisted for more than a month
      after discontinuing nicotine administration. We also identified evidence of cell
      damage and changes in cell size in the female hippocampus. These changes were
      accompanied by alterations in synaptic activity of cholinergic, noradrenergic,
      dopaminergic and serotonergic systems during nicotine administration and
      persisting for extended periods after the termination of exposure; behavioral
      alterations were commensurate with the neurochemical changes. In each case, the
      effects of adolescent nicotine differed not only from the adult, but also from
      the those seen after fetal exposure, indicating that adolescence represents a
      unique period of vulnerability for nicotine-induced misprogramming of brain cell
      development and synaptic function. Effects of nicotine on critical components of
      reward pathways and circuits involved in learning, memory and mood are likely to
      contribute to increased addictive properties and long-term behavioral problems
      seen in adolescent smokers.

PMID- 12009493
TI  - A behavioral teratogenic model of the impact of prenatal cocaine exposure on
      arousal regulatory systems.
AB  - Studies of both preclinical and human models of prenatal cocaine exposure suggest
      that one mechanism for the impact of cocaine on developing neural systems may be
      through functional alterations in monoaminergically regulated arousal systems.
      Conceptually, arousal regulation refers to a set of multimodal central nervous
      system mechanisms underlying cortical activation in response to internal and/or
      external stimulation. The emerging capacity for moment-to-moment regulation of
      states of arousal influences attentional states (e.g., posterior cortex) and
      executive functions (prefontal cortex) and thus information processing and
      learning as well as socialization. Furthermore, as a gating mechanism for
      response to novel and/or stressful conditions, arousal regulation is also a
      central construct for understanding stress reactivity and response to acute
      chronic trauma. In this paper, we review the findings of prenatal cocaine
      exposure in both preclinical and human studies with a particular focus on studies
      of neurobehavioral, neurocognitive functioning. A theoretical model of
      interactive arousal systems is presented as one possibility for integrating the
      profile of apparent cocaine-related neurobehavioral impairments in infants and
      young children prenatally exposed to cocaine.

PMID- 12009494
TI  - The effects of tobacco exposure on children's behavioral and cognitive
      functioning: implications for clinical and public health policy and future
      research.
AB  - A growing body of literature indicates that maternal smoking during pregnancy is
      associated with neurotoxic effects on children. Both animal model studies and
      human epidemiologic studies demonstrate similar effects in terms of increased
      activity, decreased attention, and diminished intellectual abilities.
      Epidemiologic studies also suggest that prenatal tobacco exposure is associated
      with higher rates of behavior problems and school failure. These findings are
      explored and their implications for child health policy and practice, and for
      research, are discussed.

PMID- 12009495
TI  - Biochemical markers related to Alzheimer's dementia in serum and cerebrospinal
      fluid.
AB  - The diagnosis of Alzheimer's disease (AD) is currently based on clinical and
      neuropsychological examination. To date there is no blood test available that can
      discriminate dementia patients from healthy individuals. In the present paper, an
      overview of the current state of knowledge on biologic markers in serum (plasma)
      and CSF is presented. The combination of characteristic plaque markers tau and
      amyloid beta may constitute a specific and sensitive CSF marker for AD. Glial
      fibrillary acidic protein and antibodies in CSF may be a marker for severe
      neurodegeneration. CSF concentrations of the oxidative stress markers 3
      nitrotyrosine, 8-hydroxy-2'-deoxyguanosine and isoprostanes are increased in AD
      patients. Serum 24S-OH-cholesterol may be an early whereas glial fibrillary
      acidic protein autoantibody level may be a late marker for neurodegeneration. To
      date, serum alpha(1)-Antichymotripsin concentration is the most convincing marker
      for CNS inflammation. Increased serum homocysteine concentrations have also been
      consistently reported in AD. In summary, a large overlap in mean concentrations
      has been observed in studies comparing AD patients with healthy controls for
      single markers. These studies together support the theory of testing several
      serum markers in combination for the diagnosis of AD.

PMID- 12009496
TI  - The challenges of developing and validating molecular and biochemical markers of
      Alzheimer's disease.

PMID- 12009497
TI  - Biochemical markers of Alzheimer's disease: wish and reality.

PMID- 12009498
TI  - Oxidized proteins & ubiquitin conjugates.

PMID- 12009499
TI  - Blood and CSF biomarkers for AD revisited: what's new, what's good, and is this
      where we should be looking?

PMID- 12009501
TI  - Neutrophils CD11b and fibroblasts PGE(2) are elevated in Alzheimer's disease.
AB  - To evaluate whether inflammation-like mechanisms present in the brain of
      Alzheimer's disease (AD) patients are reflected in the periphery, the expression
      of CD11b in peripheral blood neutrophils and the expression and activity of
      inflammatory markers in cultured skin fibroblasts were examined. We found
      significantly higher levels of CD11b in neutrophils from sporadic AD patients
      than in controls and this elevation was positively correlated with disease
      severity and progression rate of mental decline. Cultured skin fibroblasts from
      familial (FAD) and sporadic AD patients and from controls were immunopositive for
      both isoforms of cyclooxygenase with no differences between groups. In
      unstimulated culture, the production of prostaglandin-E2 in the medium was
      significantly higher in fibroblasts from sporadic AD and FAD patients than in
      controls, and this elevation was reverted by the addition of 25 microM of
      ibuprofen. Our findings provide further evidence of the presence of inflammatory
      and immuno-related markers in the periphery of AD patients and support those
      studies indicating the beneficial effects of anti-inflammatory therapy in AD.

PMID- 12009502
TI  - Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-beta
      in vitro.
AB  - Amyloid-beta protein (Abeta) is implicated in the pathogenesis of Alzheimer's
      disease because of its neurotoxicity and the ability to trigger local
      inflammation. Compounds that interact with the amino acids of the N-terminal
      region or interfere with aggregation can reduce the Abeta biologic activity. We
      evaluated the effect of heparin on Abeta (1-42) neurotoxicity and on its ability
      to activate complement and contact system. On differentiated PC12 cells, a
      reliable model of neuronal cells, heparin at the doses of 10 and 20 microg/ml
      significantly counteracted Abeta cytotoxicity as assessed by measuring MTT
      conversion. We then explored the effect of heparin on Abeta (1-42)-induced
      complement and contact system activation. Abeta (1-42) was incubated with heparin
      in presence of normal plasma as the source of complement and contact system
      factors. Heparin reduced, in a dose-dependent manner, complement and contact
      system activation, assessed by measuring the degree of C4 and high molecular
      weight kininogen cleavage. The present data show that heparin can attenuate
      neurotoxic and pro-inflammatory activity of Abeta and suggest that this drug
      could represent a new strategy to reduce the progressive neurodegeneration in AD.

PMID- 12009503
TI  - Accumulation of heparan sulfate proteoglycans in cerebellar senile plaques.
AB  - Alzheimer's disease (AD) brains are characterized by the presence of senile
      plaques (SPs), which primarily consist of amyloid beta protein (Abeta). Besides
      Abeta, several other proteins with the ability to modulate amyloid fibril
      formation accumulate in SPs, e.g. heparan sulfate proteoglycans (HSPGs).
      Cerebellar SPs are predominantly of the diffuse type, whereas fibrillar SPs are
      rarely observed. Furthermore, because of the spatial separation of non-fibrillar
      and fibrillar SPs in the cerebellum, this brain region provides a model for the
      study of the association of Abeta-associated factors with various stages of SP
      formation. In the present study, we performed an immunohistochemical analysis to
      investigate the expression of the HSPG species agrin, perlecan, glypican-1 and
      the syndecans 1-3 as well as glycosaminoglycan side-chains in cerebellar SPs. We
      demonstrated that agrin and glypican-1 were expressed in both non-fibrillar and
      fibrillar cerebellar SPs, whereas the syndecans were only associated with
      fibrillar cerebellar SPs. Perlecan expression was absent in all cerebellar SPs.
      Since fibrillar and non-fibrillar SPs may develop independently in the
      cerebellum, it is likely that agrin, glypican-1 as well as heparan sulfate
      glycosaminoglycans may contribute to the formation of both cerebellar plaque
      types, whereas syndecan only seems to play a role in the generation of cerebellar
      fibrillar plaques.

PMID- 12009504
TI  - Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy
      evidence of excess neuronal and membrane phospholipid pathology.
AB  - BACKGROUND: The presence of psychotic symptoms in Alzheimer Disease subjects
      (AD+psychosis, AD+P) is a marker for a phenotype characterized by more severe
      cognitive impairment and a more rapidly deteriorating course. Although AD+P has
      been inconsistently associated with more severe neuropathology, no prior studies
      have examined measures of neuronal and synaptic integrity. OBJECTIVE: To
      determine whether AD+P is associated with evidence of disrupted neuronal and
      synaptic integrity, as indicated by magnetic resonance spectroscopy (MRS)
      measurement of N-acetyl-L-aspartate and the membrane breakdown products,
      glycerophosphocholine and glycerophosphoethanolamine. METHODS: 31P and 1H MRS
      studies of perchloric acid extract from postmortem brain of AD subjects with and
      without a history of psychotic symptoms. All subjects were characterized for the
      presence of comorbid cortical Lewy body pathology and for history of neuroleptic
      use. Brain tissue from dorsolateral prefrontal, superior temporal, inferior
      parietal, and occipital cortex, amygdala, and cerebellum were examined in all
      subjects. Statistical analysis accounted for correlated observations across brain
      regions within-subjects. RESULTS: AD+P subjects demonstrated significant
      elevations of glycerophosphoethanolamine and significant reductions of N-acetyl-L
      aspartate. Between group differences were greatest in neocortical brain regions.
      CONCLUSION: Excess impairment of neocortical neuronal and synaptic integrity may
      provide the structural substrate underlying AD+P. Confirmation of these findings
      using in vivo MRS measures is indicated.

PMID- 12009505
TI  - Teaching old rats new tricks: age-related impairments in olfactory reversal
      learning.
AB  - Recent work suggests that normal aging may be associated with decline in
      different brain systems. In the present study, young and aged Long-Evans rats
      were tested in a spatial version of the Morris water maze dependent on medial
      temporal lobe function and also on an odor discrimination reversal task
      previously used to investigate orbitofrontal function. Aged rats acquired the
      odor discrimination problems normally but were impaired in acquiring subsequent
      reversals of the problems. A subset of the aged rats also exhibited impaired
      spatial learning in the water maze. There was no correlation between reversal
      performance and spatial learning in the aged rats, indicating that the reversal
      learning impairment was not related to decline in medial temporal lobe function.
      Instead the performance of the aged rats on the odor discrimination task
      resembled that of young rats with neurotoxic lesions of orbitofrontal cortex.
      These data indicate that rats show independent decline of different brain systems
      during normal aging and suggest orbitofrontal cortex as one prefrontal area where
      changes may be localized for further study.

PMID- 12009506
TI  - Behavioral and neural measures of auditory temporal acuity in aging humans and
      mice.
AB  - Three experiments compared auditory temporal acuity in humans and in the behavior
      and single cells in the inferior colliculus (IC) of mice, to establish the
      comparability of aging effects on temporal acuity across species, and to suggest
      a neural foundation. The thresholds for silent gaps placed in white noise (MGTs)
      were similar in young mice and young humans, and increased in some but not all
      old humans and old mice. Neural MGT in the most sensitive cells of both young and
      old mice was comparable to behavioral MGT in the young of both species, but older
      mice had more cells with very high MGT. Human listeners were selected to have
      minimal absolute hearing loss. Older mice had significant hearing loss that was
      correlated with MGT in behavioral, but not in neural, measures. Some old mice and
      some old IC cells, however, had low MGTs coupled with elevated absolute hearing
      thresholds. Age-related changes in temporal acuity appear comparable in humans
      and mice. The data suggest a common deficit in neural mechanisms.

PMID- 12009507
TI  - Aging and sex influence the anatomy of the rat anterior cingulate cortex.
AB  - Cognitive processes supported by the prefrontal cortex undergo an age-related
      decline. Until very recently, nonhuman animal models of aging have relied on the
      exclusive use of male subjects. This study was designed to investigate the
      influence of age, sex, and ovarian hormonal state on anatomy of the rat medial
      prefrontal cortex (anterior cingulate cortex). Dendritic tree extent and spine
      density were examined in young adult (3-5 mos.) and aged (20-24 mos.) male and
      female rats. Young adult females were examined either at proestrus or estrus, and
      aged females were examined in one of two reproductively senescent (estropausal)
      phases, persistent estrus or persistent diestrus. Neither the estrous cycle nor
      state of estropause influenced spine density or dendritic tree extent. However,
      the anatomy of the anterior cingulate cortex of young adult rats was sexually
      dimorphic, with males having greater dendritic spine density as well as
      arborization. While there was a reduction in density and tree extent with age for
      both sexes, this reduction was more pronounced for males, resulting in a
      disappearance of most sex differences with age. Thus the results of this study
      suggest that aging of the rodent cerebral cortex may follow a sexually dimorphic
      pattern.

PMID- 12009508
TI  - Estradiol, but not raloxifene, improves aspects of spatial working memory in aged
      ovariectomized rhesus monkeys.
AB  - Estrogen replacement therapy (ERT) alleviates many postmenopausal symptoms but
      whether it also benefits cognitive function remains controversial. Further, since
      estrogen increases the risk of breast and uterine cancers, a new class of
      compounds, called selective estrogen receptor modulators (SERMs) is being
      considered as possible alternative to ERT. The SERM raloxifene is particularly
      interesting because, like estrogen, it improves lipid metabolism and reduces bone
      loss, without adverse effects on the breast or uterus. Little is known, however,
      about its effect upon cognitive function. We used a rhesus monkey model of human
      menopause to examine the effects of ERT and raloxifene on cognitive function. We
      tested 5 aged females (21-24 years old) ovariectomized long-term (10-16 years) on
      a battery of age-sensitive tasks, including the Delayed Response (DR), the
      Delayed Non-Matching-to-Sample-10 min (DNMS-10 min) and the spatial-Delayed
      Recognition Span Test (DRST). Monkeys were tested 5 days a week on each task for
      9 consecutive months, while undergoing treatments with placebo, ethinyl estradiol
      (EE(2)), and raloxifene in alternating 28-days blocks. EE(2) transiently enhanced
      the working memory component of the spatial-DRST, but did not affect performance
      on the other tasks of the battery. Raloxifene had no effect on cognitive
      performance. These findings indicate that estradiol is able to enhance some
      aspects of spatial working memory in aged monkeys despite many years of
      estrogenic deprivation. Further, they suggest that raloxifene does not affect
      cognitive function after long-term ovarian hormone deprivation.

PMID- 12009509
TI  - Amelioration of cholinergic neurons dysfunction in aged rats depends on the
      continuous supply of NGF.
AB  - The present study was designed to examine whether NGF-induced improvement in
      morphology of senile basal forebrain cholinergic neurons persist after
      discontinuation of NGF treatment. Trophic effect of continuous intraventricular
      infusion of NGF was tested in the 4- and 28 months old male Wistar rats
      immediately after cessation of NGF and 3 or 6 weeks after termination of
      treatment. Immunohistochemical procedure for ChAT, TrkA, and p75(NTR) receptor
      has been applied to identify cholinergic cells in the basal forebrain structures.
      Using the quantitative image analyzer, morphometric and densitometric parameters
      of cholinergic cells were measured. In untreated 28-month-old rats a reduction in
      the number, size and intensity of staining of cholinergic neurons was observed in
      all basal forebrain structures. NGF significantly improved morphological
      parameters of ChAT- and TrkA-positive cells in aged rats. In 28-month-old rats
      tested within 3 and 6 weeks after discontinuation of infusion a renewed
      progressive deterioration of cholinergic phenotype of basal forebrain neurons was
      observed when compared with the NGF-treated immediately tested group. The
      parallel staining for p75(NTR) revealed normal morphology of the basal forebrain
      neurons, despite of the age of rats or the NGF treatment. Analysis of Nissl
      stained sections also showed that 28-month-old rats did not display significant
      losses of neurons in the basal forebrain when compared with the young animals.
      These findings demonstrate that senile impairment of cholinergic neurons is
      induced by a loss of cholinergic phenotype rather than an acute degeneration of
      cell bodies. NGF may be beneficial in enhancing cholinergic neurochemical
      parameters, but the protective effects seem to be dependent on the continuous
      supply of NGF.

PMID- 12009510
TI  - Sleep-related increase in activity of mesopontine neurons in old rats.
AB  - Relationships between age-related changes in sleep patterns and neuronal activity
      have received scant attention. In the present study, reticularis pontis oralis
      (RPO) and ventral tegmental nucleus of Gudden (VTN) neurons were recorded in
      unanesthetized restrained young (3 months) and old (23 months) Sprague-Dawley
      rats during wakefulness (W), slow wave sleep (SWS) and rapid eye movement (REM)
      sleep. All RPO neurons displayed a tonic activity. Firing rates were similar
      during W in young and old rats. In contrast, firing rates were higher during SWS
      in old rats (P < 0.001). In both young and old rats, firing rates increased
      significantly during REM sleep as compared to W and SWS but this increase was
      markedly greater in old rats. Neurons recorded from VTN displayed bursting
      activity at theta frequencies during W and REM sleep. The frequency of VTN
      bursting neurons was higher during REM sleep as compared to W in both groups of
      age. This difference was significantly more pronounced in old as compared to
      young rats (P < 0.001). Sleep-related hyperactivity of pontine neurons is
      discussed in terms of a possible deficit in inhibitory processes in old rats.

PMID- 12009511
TI  - Age-related disruptions in circadian timing: evidence for "split" activity
      rhythms in the SAMP8.
AB  - In the senescence-accelerated mouse of the P8 line (SAMP8), age-related changes
      in circadian timing include a decrease in amplitude of the rhythm, a slower rate
      of re-entrainment following a phase advance, and a longer free-running period
      (tau). The present study extends previous research by investigating possible
      split activity rhythms in the SAMP8. Running wheel activity was examined in 2-, 7
      , and 12-month SAMP8. Consistent with previous research, rhythms of older SAMP8
      were decreased in amplitude and showed high levels of activity during the light
      phase of the light-dark cycle. Contrary to previous reports, lengthening of tau
      in constant darkness was not observed. Additionally, activity rhythms were
      "split" in older SAMP8, demonstrated by 1) the appearance of a secondary peak in
      the periodogram at approximately half the value of tau and 2) the perceptual
      classification of actograms by naive observers. This result differs from previous
      studies in hamsters demonstrating an age-related decrease in the incidence of
      rhythm splitting. Overall, the present findings provide further evidence for age
      related disruption of circadian timing in SAMP8.

PMID- 12009512
TI  - Dietary melatonin selectively reverses age-related changes in cortical cytokine
      mRNA levels, and their responses to an inflammatory stimulus.
AB  - The basal levels of expression of mRNA of cytokines, interleukin-6 (IL-6) and
      tumor necrosis factor (TNF-alpha), in the cerebral cortex of 5 and 26 month-old
      male B6C3F1 mice have been compared. In addition, the responsivity of animals of
      differing age to an inflammatory stimulus (lipopolysaccharide, LPS) has been
      studied. Basal levels of both of these cytokine mRNAs were elevated in aged
      animals relative to the younger group. However LPS administration led to a robust
      increase in cytokine mRNA levels in the younger animals but in aged mice, there
      was either an unchanged (IL-6) or a depressed (TNF-alpha) response.
      Administration of dietary melatonin (200 ppm) to aged mice for 6 weeks prior to
      sacrifice, resulted in reduction of basal levels of cytokine mRNA to values found
      in the younger animals. Furthermore, following administration of LPS to melatonin
      fed animals, cerebral cytokine mRNA levels were significantly elevated rather
      than being unchanged or depressed. Taken together these findings reflect a trend
      in the cortices of melatonin-treated aged mice, to more closely approximate the
      status of younger mice. For comparative purposes, parallel studies were carried
      out using an immunologically active organ (spleen) and a non-neural organ with a
      low rate of cell turnover (heart muscle). In both these tissues, basal levels of
      cytokine mRNAs of animals of either age were very low, and there was a marked
      positive response to LPS. Dietary melatonin had no effect on the responses of TNF
      alpha mRNA to LPS but attenuated the reaction of splenic IL-6 mRNA, thus bringing
      the response closer to that of the younger mice.

PMID- 12009513
TI  - Melatonin reduces oxidative damage of neural lipids and proteins in senescence
      accelerated mouse.
AB  - We investigated whether long-term melatonin administration in the drinking water
      influences oxidative modification of lipids and proteins and antioxidative enzyme
      activity in brain of senescence-accelerated mice (SAM). Cerebral cortex was
      obtained in the middle of the dark period of the daily light cycle from SAMP8, a
      strain of mice prone to accelerated senescence, and from SAMR1, a senescence
      resistant strain, at 3, 6, and 12 months of age. Thiobarbituric acid-reactive
      substances (TBARS) and protein carbonyls exhibited significant age-related
      increases in both strains. Glutathione peroxidase (GPx) activity decreased
      significantly at 12 months of age in SAMP8. No age effect was found in GPx
      activity in SAMR1, or in superoxide dismutase (SOD) activity in either strain.
      Melatonin administration (2 microg/mL) via the drinking fluid beginning at 7
      months significantly decreased neural TBARS content (over 30%) in both strains
      and lowered the protein carbonyl content in the brain of SAMP8 mice. Furthermore,
      melatonin significantly augmented GPx activity (over 20%) in both strains.
      Melatonin had no effect on SOD activity. These results suggest an age-related
      increase in cerebral tissue vulnerability to oxidation in SAM that can be
      modified by melatonin, most likely through the ability of melatonin to scavenge
      oxygen free radicals and to stimulate antioxidant enzyme activity.

PMID- 12009514
TI  - Could carnosine be a naturally-occurring scavenger for acrolein and other
      reactive aldehydes in the brain?

PMID- 12009515
TI  - Hypocretin is an early member of the incretin gene family.
AB  - Recent studies have revealed that the hypothalamic hypocretin (Hcrt) neuropeptide
      system is centrally involved in mammalian REM sleep and that it may have other
      diverse physiological roles. The aims of this work were to learn when HCRT
      emerged and to test our previous hypothesis that it was created by a circular
      permutation of an incretin superfamily gene. We found HCRT in fish and believe
      the gene arose approximately 650 million years ago, in the early chordate
      lineage. Our comparison of Hcrts to the most similar members of the incretin
      peptide superfamily leads us to conclude that HCRTs are indeed incretin paralogs
      that arose by a genetic circular permutation.

PMID- 12009516
TI  - Trapping-induced changes in expression of the N-methyl-D-aspartate receptor in
      the hippocampus of snowshoe hares.
AB  - Live-trapping of animals in natural populations is one of the main ways to
      determine population processes. We examined the effects of live-trapping on the
      expression of N-methyl-aspartate (NMDA) receptor subunits in the hippocampus of
      snowshoe hares. Snowshoe hares were obtained either with or without the stress of
      live-trapping. The CA1, CA3 and dentate gyrus were dissected and analyzed for the
      presence of NMDA receptor subunits. Trapping resulted in a significant reduction
      of NMDA receptor 1 (NR1) in each of the regions examined but did not affect the
      levels of either NMDA receptor 2A or B (NR2A or NR2B). Co-immunoprecipitation
      analysis showed that the association between NR1 and NR2A was decreased in the
      trapped animals. These results suggest that stress associated with the trapping
      experience may adversely affect the structure and/or function of the NMDA
      receptor.

PMID- 12009517
TI  - Gabapentin potentiates N-methyl-D-aspartate receptor mediated currents in rat
      GABAergic dorsal horn neurons.
AB  - We previously reported that gabapentin (GBP), a widely prescribed analgesic,
      enhances N-methyl-aspartate (NMDA) receptor mediated currents only when the
      intracellular level of protein kinase C is elevated. However, it is unclear how
      the potentiation of NMDA responses by GBP can lead to pain relief. To resolve
      this issue, we combined immunocytochemical and patch recording techniques to
      study the actions of GBP on NMDA receptors in dorsal horn cells isolated from
      rats with inflammation and to determine the gamma-aminobutyric acid (GABA)
      content in the recorded cells. We found that all GBP-responsive cells are GABA
      immunoreactive and none of the GABA-negative neurons respond to GBP. Thus, GBP
      appears to enhance NMDA currents in GABAergic neurons. These observations suggest
      that GBP exerts its antinociceptive action by increasing the activity of these
      inhibitory neurons.

PMID- 12009518
TI  - Propofol facilitates the development of long-term depression (LTD) and impairs
      the maintenance of long-term potentiation (LTP) in the CA1 region of the
      hippocampus of anesthetized rats.
AB  - Memory is sensitive to the short-acting anesthetic (2,6-diisopropylphenol)
      propofol, but the underlying mechanism is little known. Here, we have examined
      the effects of propofol on synaptic plasticity in the CA1 region of the
      hippocampus of anesthetized rats. We found that low dose of propofol (20 mg/kg,
      i.p.) did not affect the basal transmission, but enhanced prominently the
      development of long-term depression (LTD) and impaired the maintenance of long
      term potentiation (LTP). The impairment of LTP maintenance and enhancement of LTD
      development may contribute to propofol-induced deficits in memory following
      propofol anesthesia.

PMID- 12009519
TI  - Amyloid precursor protein processing is separately regulated by protein kinase C
      and tyrosine kinase in human astrocytes.
AB  - Regulation of amyloid precursor protein (APP) processing by protein kinase C
      (PKC) and phosphotyrosine pathways was investigated in cultured human astrocytes.
      Phorbol 12, 13-dibutyrate (PDBu), a PKC activator, increased secretion of
      APPalpha 2-3-fold over control values, and GF109203X, a PKC inhibitor, blocked
      this effect. Similarly, platelet derived growth factor (PDGF) increased the
      secreted form of APPalpha (sAPPalpha) level two-fold, and genistein, a tyrosine
      kinase inhibitor, blocked the stimulatory effect of PDGF. Co-treatment of PDGF
      and PDBu resulted in a five-fold increase in the sAPPalpha production, and
      genistein and GF109203X did not block the stimulatory effects of PDBu and PDGF,
      respectively. These results indicate that both PKC and phosphotyrosine pathways
      are involved in APP processing in human astrocytes, but they act independently.
      The two pathways appear to converge to mitogen-activated protein kinase (MAPK)
      because PD98059, a MAPK inhibitor, blocked the effects of PDBu and PDGF on
      APPalpha secretion.

PMID- 12009520
TI  - Influence of the apolipoprotein E epsilon4 allele on human embryonic development.
AB  - Human apolipoprotein E (apoE) exists in three major isoforms encoded by distinct
      alleles (APOE epsilon2, epsilon3 and epsilon4) and has important functions in
      nerve development and repair. Inheritance of the 4 allele is a major risk factor
      for the development of Alzheimer's disease. To investigate the role of APOE
      polymorphisms in embryonic development, we analyzed the APOE genotypes of 81
      spontaneously aborted embryos and 110 adult controls using a solid-phase
      minisequencing technique. The epsilon4 allele was significantly less frequent in
      the spontaneous abortion group than in the control group (P=0.009), while the
      frequency of epsilon3 was significantly increased (P=0.005), suggesting that
      epsilon4 may have protective effects during embryogenesis. These protective
      effects might counterbalance the deleterious age-related effects of the epsilon4
      allele in natural selection.

PMID- 12009521
TI  - Stimulatory and inhibitory effects of 5-HT(1A) receptors on adrenocorticotropic
      hormone and cortisol secretion in a teleost fish, the Arctic charr (Salvelinus
      alpinus).
AB  - The serotonin(1A) (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-N
      propylamino)tetralin (8-OH-DPAT) was administrated to juvenile Arctic charr
      either by intraperitoneal (i.p.) injections or through a permanent i.p. implanted
      catheter. 8-OH-DPAT induced an elevation of plasma cortisol in non-stressed fish
      (receiving the drug through a permanent i.p. catheter), whereas 8-OH-DPAT had the
      opposite effect when administrated through a standard i.p. injection, dampening
      the rise in cortisol induced by handling and injection, an effect which was most
      pronounced at low doses of 8-OH-DPAT. In both cases, plasma levels of
      adrenocorticotropic hormone followed the same general pattern as plasma cortisol.
      The results suggests that 5-HT(1A) receptors are involved in the regulation of
      hypothalamic-pituitary-interrenal axis activity in Arctic charr, but the effect
      of 5-HT(1A) stimulation seems to vary depending on the state of the fish.

PMID- 12009522
TI  - Comparison of the effect of intrathecal endomorphin-1 and endomorphin-2 on spinal
      cord excitability in rats.
AB  - We examined and compared the effects of intrathecal (i.t.) endomorphin-1 and
      endomorphin-2 on the nociceptive flexor reflex in decerebrate, spinalized,
      unanesthetized rats. I.t. endomorphin-1 and -2 induced a dose-dependent
      depression of the flexor reflex with an initial brief facilitatory effect. The
      magnitude of reflex facilitation and depression was similar between endomorphin-1
      and -2, but the duration of depression was significantly longer for endomorphin-1
      than endomorphin-2. The results suggested that the spinal antinociceptive effects
      of endomorphin-1 and -2 are similar, with endomorphin-1 being more resistant to
      enzymatic degradation.

PMID- 12009523
TI  - Nitric oxide in the penumbra of a focal cortical necrosis in rats.
AB  - After a focal cortical freezing lesion in rats, nitric oxide (NO) end products
      were studied with microdialysis in the extracellular space of the penumbra
      throughout the whole period of secondary expansion of the cortical necrosis (i.e.
      24 h). Under baseline conditions, the dialysate concentration of nitrate
      (nitrite) was 1.8 +/- 0.78 microM (5.00 +/- 1.50 microM) in the sham-operated
      group and 2.28 +/- 0.62 microM (3.25 +/- 1.32 microM) in the trauma group. In
      animals of both groups, these parameters neither showed significant alterations
      within the observation period compared with baseline values nor between the
      groups at each individual study time point. After focal cortical trauma, NO does
      not mediate secondary necrosis expansion via the extracellular space.

PMID- 12009524
TI  - Modulation of slow cortical potentials by transcranial magnetic stimulation in
      humans.
AB  - We studied the effects of transcranial magnetic stimulation (TMS) on slow
      cortical potentials (SCPs) of the brain elicited during performance of a feedback
      and reward task. Ten healthy participants were trained to self-regulate their SCP
      amplitude using visual feedback and reward for increased or decreased amplitudes.
      Subjects participated in 27 runs (each comprising 70 trials) under three
      different conditions: single-pulse TMS delivered with the coil centered over Cz
      (vertex), over a lateral scalp position (LSP), which increased task difficulty,
      and in the absence of stimulation. Cz stimulation led to a non-significant
      enhancement of negative SCPs, while LSP stimulation led to a significant increase
      of positive SCPs. These results are consistent with the idea that enhanced task
      difficulty, as in LSP stimulation, enhances cognitive processing load leading to
      an increase of positive SCPs. Additionally, the data raise the hypothesis that
      TMS delivered to bilateral midcentral regions could modulate the amplitude of
      negative SCPs.

PMID- 12009525
TI  - Drebrin, a dendritic spine protein, is manifold decreased in brains of patients
      with Alzheimer's disease and Down syndrome.
AB  - Drebrin, located in the dendritic spines of the neuron, plays a role in the
      synaptic plasticity together with actin filaments. Although drebrin regulates the
      morphological changes of spines in neurodegenerative disease such as Alzheimer's
      disease (AD), drebrin in Down syndrome (DS) showing AD-like neuropathology has
      not been studied. We used Western blotting to determine protein levels of drebrin
      and F-actin in frontal, temporal cortex and cerebellum from patients with DS and
      AD as compared to controls. A monoclonal antibody against drebrin and F-actin was
      used. Drebrin levels were significantly decreased in frontal (means +/- standard
      deviation; DS 0.24 +/- 0.52; AD 0.16 +/- 0.14; controls 2.56 +/- 3.48) and
      temporal cortex (DS 0.07 +/- 0.11; AD 0.07 +/- 0.15; controls 1.71 +/- 1.51) and
      drebrin was also decreased when normalized with F-actin. No changes were observed
      in cerebellum. Decreased drebrin could not simply be due to cell loss (F-actin)
      or neuronal loss (comparable neuron-specific enolase between groups). Reduced
      drebrin could be responsible for or representing the loss of spine plasticity in
      DS and may be a useful indicator for the impaired arborization in
      neurodegenerative disorders.

PMID- 12009526
TI  - Stochastic resonance in human electroencephalographic activity elicited by
      mechanical tactile stimuli.
AB  - Stochastic resonance (SR) is a phenomenon in which the response of a non-linear
      system to a weak input signal is optimized by the presence of noise. The aim of
      this study was to demonstrate the experimental occurrence of SR in
      electroencephalographic (EEG) activity elicited by mechanical tactile stimuli.
      Our experiments show that EEG responses evoked by mechanical tactile stimuli in
      the region overlying the somatosensory cortical area were optimized by the
      addition of certain noise amplitudes. All subjects showed distinct SR behavior.
      The signal-to-noise ratio (SNR) of the response evoked by mechanical indentations
      of the skin was an inverted U-like function of the input noise. As the noise
      amplitude increased, SNR values became larger. A maximum value was reached with a
      particular noise amplitude value. Beyond such peak, with higher noise amplitudes,
      the curve subsided gradually. To our knowledge, this is the first documented
      evidence that such remarkable phenomenon embodies electrical processes of the
      human brain. Such behavior might explain related findings described in
      psychophysical studies.

PMID- 12009527
TI  - The endoplasmic reticulum is the main site for caspase-3 activation following
      aluminum-induced neurotoxicity in rabbit hippocampus.
AB  - We have assessed the distribution of caspase-3 in subcellular fractions from
      rabbit brain hippocampus and find that in controls the pro-caspase-3 form is
      distributed mainly in the cytoplasm. In animals treated intracisternally with the
      neurotoxin aluminum-maltolate, although pro-caspase-3 levels are higher in the
      cytosolic fractions, p17, the active caspase-3, is localized mainly in the
      endoplasmic reticulum. This distribution is confirmed by immunohistochemistry
      which demonstrates the co-localization of p17 with calnexin, a specific marker of
      the endoplasmic reticulum. Based on the apparent translocation into the
      endoplasmic reticulum of active caspase-3, an executioner of cell death, the
      results suggest that this organelle is an important site in the caspase-3
      mediated apoptosis cascade. Inhibition of the latter enzyme by directly targeting
      its main site of activation could represent a strategy to prevent this adverse
      event.

PMID- 12009528
TI  - Intralesion transplantation of serotonergic precursors enhances locomotor
      recovery but has no effect on development of chronic central pain following
      hemisection injury in rats.
AB  - The effects of intralesion grafts of serotonergic precursors on locomotor
      recovery and development of chronic pain were assessed after chronic spinal cord
      hemisection injury (SCI) in rats. Serotonin- and brain-derived neurotrophic
      factor-secreting (RN46A-B14) and RN46A-vector-only cells were transplanted into
      the site of T13 lateral hemisection 10 days following injury in immunosuppressed
      animals, and locomotor and pain related behaviors were assessed weekly for 28
      days. There were significant improvements in the degree of spontaneous locomotor
      recovery, but no significant difference was found in the magnitude of development
      of mechanical allodynia or thermal hyperalgesia in any transplant group. From
      these results, we conclude that intraparenchymal engraftment of RN46A-B14 cells
      is largely ineffective in influencing somatosensory outcomes after SCI, in
      contrast with the efficacy of dorsal intrathecal placement.

PMID- 12009529
TI  - Evidence for in vivo production of Humanin peptide, a neuroprotective factor
      against Alzheimer's disease-related insults.
AB  - An unbiased functional screening with brain cDNA library from an Alzheimer's
      disease (AD) brain identified a novel 24-residue peptide Humanin (HN), which
      suppresses AD-related neurotoxicity. As the 1567-base cDNA containing the open
      reading frame (ORF) of HN is 99% identical to mitochondrial 16S ribosomal RNA as
      well as registered human mRNA, it was elusive whether HN is produced in vivo.
      Here, we raised anti-HN antibody and found that long cDNAs containing the ORF of
      HN (HN-ORF) produced the HN peptide in mammalian cells, dependent on the presence
      of full-length HN-ORF. Immunoblot analysis detected a 3-kDa protein with HN
      immunoreactivity in the testis and the colon in 3-week-old mice and in the testis
      in 12-week-old mice. HN immunoreactivity was also detected in an AD brain, but
      little in normal brains. This study suggests that HN peptide could be produced in
      vivo, and would provide a novel insight into the pathophysiology of AD.

PMID- 12009530
TI  - Modulatory effects of ketamine on catecholamine efflux from in vivo cardiac
      sympathetic nerve endings in cats.
AB  - With the use of the microdialysis technique, we examined the modulatory effect of
      ketamine on catecholamine efflux from in vivo cardiac sympathetic nerve endings.
      A dialysis probe was implanted in the left ventricular myocardium, and dialysate
      norepinephrine (NE) levels in anesthetized cats were measured with liquid
      chromatogram-electrical detection. A 60-min occlusion of the left anterior
      descending coronary artery caused increases in dialysate NE levels. Through the
      dialysis probe, locally applied ketamine (10 mM) augmented the dialysate NE
      responses to coronary occlusion in the presence and absence of desipramine
      (membrane NE transport blocker). Thus, the ketamine-induced NE increment is not
      mediated through the neuronal NE transporter. The sympathomimetic action of
      ketamine may augment the NE efflux evoked by myocardial ischemia.

PMID- 12009531
TI  - Theiler's virus infection induces the expression of cyclooxygenase-2 in murine
      astrocytes: inhibition by the anti-inflammatory cytokines interleukin-4 and
      interleukin-10.
AB  - Theiler's murine encephalomyelitis virus (TMEV) causes an acute encephalomyelitis
      followed by a persistent infection of the central nervous system (CNS) resulting
      in a chronic inflammation and axonal demyelination in susceptible strains of
      mice. The pathogenesis of TMEV-induced demyelinating disease remains unknown, but
      infection of brain glial cells is a critical factor for virus persistence in the
      CNS. In the present study we investigated the effects of the anti-inflammatory
      cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) on the production of
      inflammatory mediators, such as prostaglandins, after infection of primary
      astroglial SJL/J murine cultures with TMEV. This infection resulted in a time
      dependent transcription of the gene encoding cyclooxygenase-2 (COX-2) and an
      increased production of prostaglandin E2 (PGE(2)). Both, IL-4 but mainly, IL-10
      (1 and 10 ng/ml) decreased the TMEV-induced expression of COX-2 as well as the
      synthesis of PGE(2). Interestingly, treatment with IL-10 completely abrogated COX
      2 induction. The molecular mechanisms involved in the regulation of COX-2
      expression by TMEV are unknown, but the effects of anti-inflammatory cytokines
      may involve the inhibition of the transcription factor nuclear factor B activity
      and lead to strategies capable of interrupting the inflammatory cascade triggered
      by TMEV in brain glial cells.

PMID- 12009532
TI  - Attenuated drinking response induced by angiotensinergic activation of
      subfornical organ projections to the paraventricular nucleus in estrogen-treated
      rats.
AB  - The present study was carried out to examine whether estrogen modulates the
      drinking response caused by activation of neural pathways from the subfornical
      organ (SFO) to the hypothalamic paraventricular nucleus (PVN) in the female rat.
      Microinjection of angiotensin II (ANG II) into the SFO elicited drinking in
      ovariectomized female rats that were treated with either propylene glycol (PG)
      vehicle or estradiol benzoate (EB). The amount of water intake induced by the ANG
      II injection was significantly greater in the PG-treated than in the EB-treated
      animals. In both groups, previous injections of either saralasin, an ANG II
      antagonist, or phentolamine, an alpha-adrenoceptor antagonist, bilaterally into
      the PVN resulted in the significant attenuation of the drinking response to ANG
      II, whereas similar injections of saline vehicle into the PVN were without
      effect. These results suggest that the circulating estrogen may act to reduce the
      drinking response that is mediated through angiotensinergic and alpha-adrenergic
      mechanisms in the PVN in response to angiotensinergic activation of SFO efferent
      projections.

PMID- 12009533
TI  - Anatomical evidence of subcortical contributions to the orientation selectivity
      and columns of the cat's primary visual cortex.
AB  - Physiological studies have demonstrated a subcortical origin for orientation
      selectivity and the orientation columns of the primary visual cortex. However,
      there are no anatomical data showing how subcortical cells contribute to this
      important property. Optical imaging, combined with 1,1'-dioctadecyl-3,3,3,3'
      tetramethylin-docarbocyanine perchlolate (DiI) and biocytin retrograde tracing,
      reveals that relay cells projecting to a single orientation column representing
      the horizontal meridian were clustered within 300 microm in the dorsal lateral
      geniculate nucleus (LGN). Interestingly, some labeled cells were located on a
      line parallel to an iso-elevation line in the LGN. Thus, according to the
      quantitative projection of the visual field to the LGN (J. Comp. Neurol. 143
      (1971) 101), their receptive fields must distribute horizontally in alignment in
      the visual field providing the first anatomical evidence for Hubel and Wiesel's
      model of simple cell receptive fields (J. Physiol. 160 (1962) 106).

PMID- 12009535
TI  - Many patients with stroke are never seen by neurosurgeons.

PMID- 12009534
TI  - Release patterns of excitatory and inhibitory amino acids within the hypothalamic
      supraoptic nucleus in response to direct nitric oxide administration during
      forced swimming in rats.
AB  - The effect of direct intrahypothalamic nitric oxide (NO) administration on the
      release of selected amino acids in the hypothalamic supraoptic nucleus (SON) with
      and without concomitant forced swimming was investigated. Adult male Wistar rats
      were chronically fitted with U-shaped microdialysis probes in the SON and forced
      to swim for 10-min in 20-degree C warm water. Thirty-min microdialysis samples
      were collected before, during and after the forced swimming period while NO was
      administered into the SON via microdialysis. The results show that NO
      administration in combination with forced swimming affects the release of
      aspartate, glutamate, taurine, and gamma aminobutyric acid (GABA) in different
      patterns. Whereas the release of the excitatory amino acids aspartate and
      glutamate was triggered only during NO administration and forced swimming, the
      inhibitory amino acids GABA and taurine were found in the extracellular fluid in
      increased concentrations also after the treatment. These data indicate that NO
      administration differently affects the release of excitatory and inhibitory amino
      acids within the SON. Thus, SON neurons which contain high concentrations of
      neuronal NO synthase, might contribute to the regulation of their own secretory
      activity by releasing NO that controls the orchestrated release of excitatory and
      inhibitory amino acids from axon terminals of afferences and interneurons as well
      as release from glial cells.

PMID- 12009536
TI  - Endovascular therapy for intracranial aneurysms: a historical and present status
      review.
AB  - Beginning in the 1960s, neurosurgeons and radiologists have made attempts to
      treat intracranial aneurysms using nonclip techniques. The evolution of such
      therapy has included acrylics, metallic particles, balloons, electric current,
      and nondetachable and detachable coils. This article will chronologically review
      these various techniques and the papers that reported their results so that the
      reader can understand how endovascular therapy developed and the position it
      currently holds in the treatment of intracranial aneurysms.

PMID- 12009538
TI  - Prognosis and prognostic factors in nonaneurysmal perimesencephalic hemorrhage: a
      follow-up study in 29 patients.
AB  - BACKGROUND: Perimesencephalic nonaneurysmal hemorrhage is a benign form of
      subarachnoid hemorrhage with a low risk of rebleeding. The authors conducted a
      retrospective study to investigate the prognosis, possible prognostic factors,
      and long-term natural history in perimesencephalic nonaneurysmal subarachnoid
      hemorrhage (PNSH). METHODS: This report contains a retrospective analysis of 29
      patients with PNSH who were followed from 1 month to 8 years with an average
      follow-up period of 5.4 years. We evaluated computed tomography (CT) scan
      features; clinical grade; loss of consciousness during hemorrhage; ventricular
      ratio; angiographic spasm; complications such as ischemic complications, early
      rebleeding, late rebleeding, epilepsy, hydrocephalus, and fixed ischemic deficit;
      and outcome. RESULTS: There were 7 men and 22 women, and the ages ranged from 22
      to 69 years (mean 49.5 years). In the group with PNSH 93% of the patients were in
      grade I-II, as compared to 70.8% of patients with non-PNSH according to the Hunt
      and Hess system. Loss of consciousness during hemorrhage was detected in 9
      patients (31%). We observed acute hydrocephalus in 4 patients (13.7%). The first
      cerebral four-vessel angiograms disclosed vasospasm in 3 patients (10.3%).
      Patients with PNSH have the best outcome according to the activities of daily
      living (ADL) grading system when compared with other groups of patients with
      negative angiogram (aneurysmal pattern and invisible blood). CONCLUSION: This
      study provides evidence that patients with PNSH have an uncomplicated course and
      a particularly favorable outcome.

PMID- 12009541
TI  - Angiographically occult epidural arteriovenous fistula of the craniocervical
      junction.
AB  - BACKGROUND: Spinal dural and intradural arteriovenous fistulas (AVFs) have been
      the subject of numerous reports but purely epidural AVFs causing venous
      congestion within the spinal cord are rare. CASE DESCRIPTION: We describe a
      patient with an exclusively epidural arteriovenous fistula and congestive
      myelopathy. There are three interesting features of this case as described below:
      1) The presence of a purely epidural AVF of the cranio-cervical junction.
      According to our knowledge this is the first case of an AVF in this location. 2)
      The lesion was angiographically occult. This was probably because of the
      extremely slow flow of the fistula. 3) Despite the negative angiograms,
      exploratory surgery was conducted because of positive clinical and MR findings.
      CONCLUSIONS: Epidural AVF/AVM of the foramen magnum should be considered in the
      differential diagnosis in patients with chronic myelopathy, even if cranial and
      spinal angiograms are negative. In these cases, we recommend that if clinical and
      radiological investigations strongly suggest the presence of an arteriovenous
      fistula, surgical exploration should be performed.

PMID- 12009543
TI  - Traumatic false aneurysm of the middle meningeal artery causing an intracerebral
      hemorrhage: case report and literature review.
AB  - BACKGROUND: Traumatic false aneurysms of the meningeal arteries are rare. We
      report an unusual case of an intracerebral hematoma caused by the rupture of a
      traumatic aneurysm of the middle meningeal artery. CASE DESCRIPTION: A 64-year
      old woman suffered a massive spontaneous intracerebral fronto-temporal
      hemorrhage. Cerebral angiogram revealed a pseudoaneurysm of the middle meningeal
      artery. At operation, a skull fracture was discovered in the vicinity of the
      aneurysm. The patient died the day after surgery. CONCLUSION: Although rare,
      traumatic meningeal aneurysms should be considered as a possible cause of
      cerebral hematoma. Because of their potential morbidity and mortality, they must
      be detected and treated rapidly.

PMID- 12009545
TI  - Epidural B cell non-Hodgkin's lymphoma associated with chronic subdural hematoma.
AB  - BACKGROUND: Chronic subdural hematoma generally occurs in elderly patients, who
      are also prone to neoplasm. However, the association of chronic subdural hematoma
      and intracranial neoplasm is rare. CASE DESCRIPTION: An elderly woman harboring a
      chronic subdural hematoma underlying an epidural extension of a malignant B cell
      non-Hodgkin's lymphoma is reported. Infiltration of the tumor and obstruction of
      the dural veins with stasis and rupture of the capillary net may have been the
      mechanism that led to formation of the hematoma. CONCLUSIONS: In elderly patients
      harboring chronic subdural hematoma with mural isodensity on CT who have no
      history or an uncertain history of head trauma, one should consider the
      possibility of neoplasm, although it is rare. Chronic subdural hematoma
      associated with epidural extension of B cell non-Hodgkin's lymphoma is
      exceptional. Screening for other systemic manifestations should be carried out.
      Radiotherapy, alone or in combination with chemotherapy, should be considered
      after surgical removal.

PMID- 12009546
TI  - Abducens nerve schwannoma: a case report and review of the literature.
AB  - BACKGROUND: Schwannomas of the abducens nerve are extremely rare tumors; only 10
      cases have been reported so far. The tumor may be located within the cavernous
      sinus (CS) or more commonly at the prepontine region. Patients usually present
      with VIth cranial nerve paresis. CASE DESCRIPTION: We report a case of a 42-year
      old male patient who presented with headache, vertigo, and hearing deficit, but
      no symptoms or signs related to a VIth cranial nerve impairment. Computed
      tomography and magnetic resonance imaging showed a large mass with a ring-like
      contrast enhancement in the prepontine area. Surgical treatment, via a simple
      retrosigmoid suboccipital approach, revealed a schwannoma originating from the
      VIth cranial nerve at its prepontine portion. Postoperative histological
      examination confirmed the diagnosis of schwannoma, and the patient had only a
      VIth cranial nerve palsy, which resolved during long-term follow-up. CONCLUSIONS:
      Abducens schwannomas are rare tumors, representing less than 1% of all
      intracranial schwannomas in our clinic and about 13% of oculomotor nerve
      schwannomas reported in the literature. These lesions can be mainly divided into
      tumors originating from the intracavernous portion of the VIth cranial nerve or
      more commonly from the cisternal part of the nerve, leading to a lesion in the
      prepontine region. In such cases, with no invasion of the cavernous sinus,
      radical tumor resection with preservation of the abducens nerve can be performed
      via a simple suboccipital retrosigmoid approach.

PMID- 12009548
TI  - A four-year experience with a stereotactic computer in a small neurosurgical
      department.
AB  - BACKGROUND: A stereotactic computer with a mechanical, proprioceptive arm was
      acquired in 1996. The aim of this report is to review the 4-year experience with
      frameless, computer-aided stereotaxy in a small neurosurgical department.
      METHODS: From 1996 to 1999 the computer was used for 121 operations. The surgical
      files from these operations were either retrospectively or prospectively
      registered. Patient and computer data, type of surgery, complications and number
      of surgeons were noted. The versatility, benefits, and drawbacks of the
      stereotactic computer were evalued based on these findings. RESULTS: Seven
      surgeons performed a total of 121 computer-assisted operations. The procedures
      consisted of 63 stereotactic tissue samplings, 44 craniotomies, 7 abscess
      punctures and 3 insertions of intracerebral devices (shunts and microelectrodes).
      Technical complications were seen in 6 cases (4.8%), but this did not affect the
      surgical outcome. CONCLUSIONS: The stereotactic computer has enabled the
      department to broaden its spectrum of procedures. High precision surgery such as
      stereotactic biopsy has been possible without the use of a framebased system. The
      results indicate that even small neurosurgical units with a limited number of
      procedures can safely and successfully implement neuronavigation in daily
      routines.

PMID- 12009549
TI  - Calvarial tuberculosis.
AB  - BACKGROUND: Calvarial tuberculosis is rare, even in areas where tuberculosis is
      endemic. Primary calvarial tuberculosis, with no evidence of tuberculosis
      elsewhere in the body is a rarer entity. METHODS: Seven cases of calvarial
      tuberculosis are presented. The relevant clinicoradiological features and
      management are discussed. RESULTS: Two cases of primary calvarial tuberculosis
      could only be diagnosed after surgery. The other cases were diagnosed with the
      help of fine needle aspiration cytology (FNAC) and biopsy. CONCLUSION: A high
      index of suspicion and awareness of this condition may lead to more cases being
      diagnosed early. Surgery may be avoided in selected cases that can be treated
      primarily with antitubercular therapy.

PMID- 12009552
TI  - Psychiatry consultation service in neurosurgery.

PMID- 12009557
TI  - Perimesencephalic nonaneurysmal subarachnoid hemorrhage: what is it? what are we
      missing?

PMID- 12009558
TI  - ACF with and without plates.

PMID- 12009560
TI  - Discrimination of emotional facial expressions in a visual oddball task: an ERP
      study.
AB  - Several ERP studies have shown an orienting complex, the N2/P3a, associated to
      the detection of stimulus novelty. Its role consists in preparing the organism to
      process and react to biologically prepotent stimuli. Whether this N2/P3a: (1)
      could be obtained with complex visual stimuli, such as with emotional facial
      expressions; and (2) could take part in a complex discrimination process has yet
      to be determined. To investigate this issue, event-related potentials were
      recorded in response to repetitions of a particular facial expression (e.g.
      sadness) and in response to two different deviant (rare) stimuli, one depicting
      the same emotion as the frequent stimulus, while the other depicted a different
      facial expression (e.g. fear). As expected, deviant stimuli evoked an N2/P3a
      complex of larger amplitude than frequent stimuli. But more interestingly, when
      the deviant stimulus depicted the same emotion as the frequent stimulus the
      N2/P3a was delayed compared to the response elicited by the different-emotion
      deviant. The N2/P3a was thus implicated in the detection of physical facial
      changes, with a higher sensitivity to changes related to a new different
      emotional content, perhaps leading to faster adaptive reactions.

PMID- 12009561
TI  - Human perceptual learning in the peripheral visual field: sensory thresholds and
      neurophysiological correlates.
AB  - Perceptual learning in the peripheral visual field was studied in 24 adults using
      vernier targets. The aim was to relate perceptual improvements to changes of
      electrical brain activity. Thresholds were measured before, during, and after
      training, and on the next day. During training, the subjects passively looked at
      suprathreshold targets, and EEG activity was recorded from 30 electrodes over the
      occipital brain areas. Mean evoked potentials were computed for the first and
      second block of 1200 stimulus presentations, and the scalp topography of visual
      evoked potential (VEP) activity was analysed. Only for the stimulated area,
      training resulted initially in increased thresholds that, however, decreased
      significantly after consolidation. Electrical brain activity displayed smaller
      field strength and altered topography after training. Some of the effects were
      caused by habituation or adaptation to the training stimuli resulting in less
      efficient neurophysiological processing. The topographical changes indicate that
      different neuronal elements were activated after perceptual learning.

PMID- 12009562
TI  - Probing the response selection bottleneck with a cardiac measure: individual
      differences in strategy for a psychological refractory period task.
AB  - We examined the coordination of processing streams when two reaction stimuli are
      presented with minimal temporal separation (the psychological refractory period,
      PRP, paradigm). We tested the hypothesis that individuals that grouped responses
      to the two stimuli would schedule response preparation later than those not
      grouping their responses would. Performance measures were combined with a cardiac
      measure interpreted as an index of response inhibition. Forty-two college-aged
      participants performed an auditory choice task followed in 50, 100 or 400 ms by a
      visual choice reaction time (RT) task. Performance results replicated prior work.
      The timing of cardiac inter-beat intervals (IBIs) showed that participants
      grouping their reactions did appear to delay response preparation; while Non
      Groupers promptly initiated response selection for the initial task. These
      results generally supported the importance of preparation for understanding the
      coordination of processing streams.

PMID- 12009564
TI  - Cytokines and chemoattractants in allergic inflammation.
AB  - It is now generally accepted type 2 T helper (Th2) cytokines and some
      chemoattractants play an essential role in the pathogenesis of the allergic
      inflammation. The effects of Th2 cytokines, such as interleukin (IL)-4, IL-5, IL
      9, and IL-13, account for virtually all the pathophysiological manifestations of
      allergy and asthma. Moreover, both Th2 cells and the effector cells usually
      present in the areas of allergic inflammation (basophils, mast cells, and
      eosinophils) express chemoattractant receptors, such as CCR3, CCR4, CCR8 and
      CRTH2. Therefore, interactions of eotaxin(s), eotaxin/CCL11, RANTES/CCL5, and MCP
      1/CCL2, MCP-2/CCL8, MCP-3/CCL7, MCP-4/CCL13 with CCR3 are responsible for the
      recruitment of basophils, eosinophils and mast cells, whereas interactions of
      CCR4 with MDC/CCL22 or TARC/CCL17, CCR8 with I-309/CCL1, and CRTH2 with
      prostaglandin D(2) play a critical role in the allergen-induced recruitment of
      Th2 cells in the target tissues of allergic inflammation. The demonstration that
      Th2-polarized responses against allergens represent the triggering event for the
      development of allergic diseases, together with the recognition that some
      chemoattractants are responsible for the recruitment of both Th2 cells and other
      effector cells of allergic inflammation, can provide the conceptual basis for the
      development of new therapeutic strategies in allergic conditions.

PMID- 12009565
TI  - The role of innate mediators in inflammatory response.
AB  - Cytokines produced by innate immune response can profoundly influence the
      subsequent adaptive immunity. IL-15 and -18 are two of several mediators produced
      by macrophages that perform such a function. Here we present recent data mainly
      from our own laboratory illustrating the important role of IL-15 and -18 in the
      induction and perpetuation of chronic inflammation during experimental and
      clinical rheumatoid synovitis.

PMID- 12009566
TI  - Positive and negative regulation of pathogen induced dendritic cell function by G
      protein coupled receptors.
AB  - The induction of IL-12 from dendritic cells (DC) is a major initiating step in
      host resistance to intracellular pathogens. We have studied the regulation of
      this response using an in vivo model in which IL-12 production by splenic
      CD8alpha+ DC is followed after injection of a soluble extract (STAg) of the
      protozoan parasite Toxoplasma gondii. Our findings indicate that the potent IL-12
      response observed is highly dependent on both the chemokine receptor CCR5 and
      G(i)-protein coupled signaling. In addition, we have examined the basis of the
      unresponsiveness of DC to secondary STAg injection which occurs following primary
      exposure to this parasite stimulus. Our results demonstrate that this refractory
      state correlates with the down-regulation of CCR5 expression on DC which, in
      turn, appears to depend on the induction of endogenous lipoxin A(4) (LXA(4)), a
      product of arachidonic acid metabolism. Since LXA(4) is known to also signal
      through a G-protein coupled receptor pathway, these findings taken together
      support a major role for G-protein signaling in the regulation of microbial
      induced DC function.

PMID- 12009567
TI  - B cell diversity and longevity in systemic autoimmunity.
AB  - Despite much investigation, the nature of the primary disturbances that culminate
      in the production of pathogenic autoantibodies remains imprecise. However, major
      advances in the understanding of the genetics, the cellular and the molecular
      basis of pathogenic autoreactivity have been achieved in recent years. Not only B
      cells play a paramount role in systemic autoimmunity, but their role is not
      limited to secretion of autoantibodies. Under certain experimental conditions, B
      cells can activate memory T cells, and can process and present self-antigens to
      naive T cells, implying the existence of an antibody-independent mechanism for
      tissue injury in systemic autoimmune diseases, such as lupus. In both the mouse
      and the human disease, B cells secreting autoantibodies exhibit features which
      suggest that they are selected by specific autoantigens. Factors, such as BAFF,
      that support differentiation of selected B cells into mature long-lived B cells
      may be critical in generating deleterious autoimmune responses, at least in
      experimental animals. During these selection processes, the amount of signals
      received by the B cells are fine-tuned for optimal transmission, and kinases and
      phosphatases control most activities. Since a tight regulation of signaling
      pathways is required to prevent overt autoimmunity, faulty cell signaling may
      cause or exacerbate disorders of the immune system. Several observations showing
      altered expression of signaling molecules in T and B lymphocytes from patients
      with human lupus suggest that the subversion of immune receptor signaling could
      account for the hyperproduction of autoantibodies.

PMID- 12009568
TI  - Inherited disorders of IL-12- and IFNgamma-mediated immunity: a molecular
      genetics update.
AB  - In the last 6 years, considerable advances have been made in the molecular
      analysis of a rare clinical syndrome: Mendelian susceptibility to mycobacterial
      disease (MSMD). Infection with poorly virulent environmental non-tuberculous
      mycobacteria (NTM) or vaccination with bacillus Calmette-Guerin (BCG) may cause
      disseminating and even fatal disease in individuals suffering from this syndrome.
      Mutations in five genes (IFNGR1, IFNGR2, STAT1, IL12B and IL12RB1) have been
      shown to be responsible for MSMD and further allelic heterogeneity accounts for
      the existence of nine distinct inherited disorders. All of these disorders are
      caused by impaired IFNgamma-mediated immunity. These results have important
      medical and biological implications. In this report, we update the disease
      causing mutations reported in the literature.

PMID- 12009569
TI  - Immunomodulation by parasites: high mobility group 2 (HMG-2) protein is a
      putative intracellular mediator for fucosylated sugars of Schistosoma mansoni.
AB  - Fucosylated sugars in Schistosoma mansoni possess immunomodulatory properties. In
      order to gain insights to the mechanisms involved, attempts were made to identify
      host immune cell molecules that specifically recognize these sugars. On Western
      blots, specific binding of synthetic biotinylated fucose sugars to proteins of
      approximately 25-27kDa was observed. Three proteins were isolated by affinity
      chromatography and subjected to protein sequencing. The determined N-terminal
      sequences and that of tryptic peptides of two proteins did not show homology to
      known sequences in the NCBI database. The third was identified as a member of the
      high mobility group 2 (HMG-2) proteins. In vitro stimulation of mouse spleen
      cells with Lewis(x) sugars up-regulated the expression of HMG-2 mRNA. These data
      suggest that HMG-2 protein may function as a putative intracellular
      receptor/mediator for fucosylated sugars of parasites.

PMID- 12009570
TI  - Constitutive and inflammatory induction of alpha and beta chemokines in human
      first trimester forebrain astrocytes and neurons.
AB  - Chemokine effects on leukocyte infiltration into the central nervous system (CNS)
      are key events in the inflammatory processes of neuroimmunologic and
      neuroinfectious diseases. Because, chemokines may play important roles in
      proliferation and differentiation of brain cells and in the initiation and
      progression of CNS inflammatory disorders, we analyzed constitutive and
      inflammatory-induced expression of alpha and beta chemokines in human first
      trimester forebrain cells. Constitutive induction of IL-8, MIP-1alpha, MIP-1beta,
      MCP-1 and regulated on activation, normal T-cell expressed, and secreted (Rantes)
      was detected in cryostat sections of embryonic forebrains in an age-dependent
      manner. Dissociated cell cultures were studied for spontaneous chemokine
      induction and after stimulation with the trypanosome lymphocyte triggering factor
      (TLTF), a novel trypanokine secreted by African trypanosomes that triggers a
      complex of immune responses. LPS and variant surface glycoprotein (VSG) were used
      as controls. In cultures, unstimulated cells expressed minimal chemokine levels
      except for Rantes. In response to TLTF and LPS, but not VSG, all chemokines were
      highly induced at the mRNA and protein levels in a dose- and age-dependent
      manner. Combined assays (in situ hybridization and immunohistochemistry) revealed
      that astrocytes and neurons are major sources for chemokines. These results
      illustrate the ability of resident brain cells to constitutively express
      chemokine genes, which may suggest an important role for chemokines during brain
      development. Furthermore, TLTF-induced chemokine expression in astrocytes and
      neurons indicate the capacity of TLTF to provoke neuroinflammation in the brain,
      which may have important therapeutic implications for the neurological
      manifestations of African trypanosomiasis.

PMID- 12009571
TI  - Cytokine expression by attenuated intracellular bacteria regulates the immune
      response to infection: the Salmonella model.
AB  - Attenuated Salmonella strains have shown excellent efficacy as mucosal vaccine
      delivery systems. In the present report, several recombinant strains of
      Salmonella enterica serovar Typhimurium, engineered to express defined murine
      cytokines, were used to study their potential immunoregulatory capacity in the
      mouse model of typhoid fever. Specifically, recombinant strains expressing IL-2
      (known as GIDIL2) or TNF-alpha (GIDTNF) were compared with the parental, non
      cytokine-secreting, strain (BRD509) for their ability to induce a variety of
      immune responses in susceptible BALB/c mice. Our findings indicate that
      bacterially-expressed cytokines are functional in vivo and do induce a unique
      pattern of responses, quite distinct from that induced by BRD509 organisms. Both
      the type and magnitude of specific immune parameters were affected. These
      included the capacity to induce an inflammatory response resulting in a state of
      profound splenomegaly and hepatomegaly, activation of individual immune cells
      (particularly macrophages and other myeloid lineage cells), and the induction of
      nitric oxide (NO) secretion. Furthermore, a structural analysis using light as
      well as electron microscopy was undertaken to examine the host cellular response
      to infection with the different bacterial strains. The results indicate that
      cytokine expression by the invading pathogen can dramatically influence host
      immunity from a very early stage following infection. These findings may well
      have important consequences for the potential utilization of bacterial vector
      encoded cytokines in immunoregulation in different disease settings.

PMID- 12009572
TI  - Downregulation of apoptosis in the target tissue prevents low-dose streptozotocin
      induced autoimmune diabetes.
AB  - 3,7-dimethyl-1-(5-oxohexyl) xanthine, pentoxifylline (PTX) is shown to affect
      cytokine-induced apoptosis in several experimental models and clinical
      conditions. It had been also shown to prevent insulitis and hyperglycemia in non
      obese diabetic (NOD) mice, and mice and rats susceptible to diabetes induction
      with multiple low-doses of streptozotocin (MLD-STZ). We therefore analysed the
      development of diabetes and apoptosis of pancreatic beta islet cells in CBA/mice
      after diabetes induction with MLD-STZ. We have evaluated the effect of PTX on the
      level of apoptosis in the islet at different time intervals after diabetes
      induction. Complementary histological and immunohistochemical studies and
      analyses of the expression of cytokines and nitric oxide have also been done. It
      was concluded that PTX significantly attenuated apoptosis of the beta-cells in
      the islet and suppressed the induction of diabetes. Our data are compatible with
      the notion that interferon-gamma (IFN-gamma)/tumor necrosis factor (TNF)/nitric
      oxide (NO)-induced apoptosis of beta-cells in experimental diabetes is attenuated
      by PTX.

PMID- 12009573
TI  - Invasive fungal infections: evolving challenges for diagnosis and therapeutics.
AB  - Invasive fungal infections (IFI) parallel the explosive increase in the
      immunocompromized patient population, and are characterized by diagnostic
      difficulties and extreme mortality. Candidemia in a tertiary referral hospital in
      the Middle East confirms the current epidemiologic shift in this common blood
      stream pathogen towards non-malignancy cases (38%) and antifungal prophylaxis
      failure (20%), high presentation sepsis scores and attributable mortality (32%).
      Invasive aspergillosis (IA) is also associated with high mortality. Use of non
      invasive computerized tomographic (CT) radiologic scanning linked to early
      administration of high dose liposomal amphotericin B (LAB) is associated with a
      reduced mortality of 9.5% compared to historical experience of 28%.Life
      threatening invasive aspergillosis also occurs in patients who are less obviously
      immunocompromized. Investigations may reveal subtle immune deficits which could
      place the patient at some risk for an invasive mycosis. Antifungal treatment used
      in combination with progenitor cell growth factors and gamma-interferon has
      proved successful in such situations of progressive fungal disease unresponsive
      to antifungal therapy alone. Pharmacologic remodeling of existing compounds by
      lipidisation reduces both the toxicity denominator and the efficacy numerator of
      the therapeutic index when compared to the parent drug. A comparative dose study
      of liposomal amphotericin B in aspergillosis has demonstrated equi-efficacy,
      generated debate over the ability of the controlled clinical trial to be capable
      of assessing antifungal efficacy, and illustrated that recovery from an invasive
      fungal infection may require maximum tolerated doses and immunomanipulation.
      Several new antifungal strategies are under clinical investigation. These include
      reformulating existing antifungals, exploitation of the growing knowledge of
      virulence factors to synthesize antagonists, immune reconstitution and
      immunoprotection. An interim analysis of an ongoing placebo controlled study of
      recombinant interleukin-11 to assess its efficacy in reducing sepsis in leukemia
      patients through prevention of chemotherapy induced gut epithelial cell
      apoptosis, has demonstrated a difference in the two study arms in sepsis rates
      and preservation of gastrointestinal epithelial cell integrity. The unique and
      special challenges presented by the dynamic epidemiologics of invasive fungal
      infections are demanding and attracting considerable responses, in the fields of
      diagnosis and therapeutics. Current strategies need considerable improvement, yet
      ongoing collaborative efforts will have a positive impact on our understanding of
      the fungus-host interaction and ultimately our ability to offer better care for
      our patients with invasive mycoses.

PMID- 12009574
TI  - HLA and in vitro susceptibility to HIV infection.
AB  - Since the beginning of the epidemic of acquired immunodeficiency syndrome (AIDS),
      evidence has accumulated that genetic factors are involved in the pathogenesis of
      the disease. Among the candidate molecules suspected to control susceptibility to
      human immunodeficiency virus (HIV) infection and fast or slow progression of AIDS
      are the human leukocyte antigens (HLA). Investigating HLA-HIV correlation was
      mainly performed by investigating cohorts of patients with HIV/AIDS for a period
      of time and then statistically correlating certain features of AIDS with
      particular HLA alleles. This type of in vivo investigations resulted in the
      generation of an immense literature on the subject with so many HLA alleles being
      found to correlate with certain features of AIDS. Because of the complexity of
      AIDS pathogenesis and the involvement of many factors in the disease process, the
      different investigators failed to agree on the involvement of certain HLA
      molecules in AIDS pathogenesis. Some reports deny, or fail to confirm the
      existence of association between HLA and HIV progression to AIDS. This is
      probably due to the different ethnic backgrounds of the populations studied, the
      complexity of the HLA system, and to the ways these studies were conducted. This
      article briefly addresses our current knowledge on the HLA-HIV correlation in
      vivo and discusses alternative in vitro studies.

PMID- 12009575
TI  - A study of five human cytokine genes in human essential hypertension.
AB  - With a view to evaluating the putative involvement of cytokine gene variants in
      human essential hypertension, we carried out an association (case-control) study
      on 174 unrelated nationals (81 hypertensives and 93 normotensives) from the Abu
      Dhabi Emirate (UAE), a genetically homogeneous population also characterised by
      the absence of traditional confounding factors such as alcohol consumption and
      smoking. To that end, we targeted our investigation to five candidate gene loci
      transforming growth factor beta1 (TGF-beta1), interferon gamma (IFN-gamma),
      epidermal growth factor (EGF), interleukin-1 beta (IL-1beta) and tumour-necrosis
      factor (TNF-alpha) genes. We investigated the distribution of genotypes and
      alleles of the six following dimorphic variants: TGF-beta1(*)10(T>C) and TGF
      beta1(*)25(G>C), located at codons 10 and 25, respectively, of TGF-beta1; T874A
      in intron 1 of IFN-gamma; G61A in exon 1 of EGF; TaqI dimorphism at +3962 (exon
      5) of IL-1beta; and -308A>G in the promoter of TNF-alpha. These six bi-allelic
      markers were visualised by methods based on the techniques of amplification
      refractory mutation system-polymerase chain reaction (for TGF-beta1, IFN-gamma,
      EGF and TNF-alpha) and by polymerase chain reaction-TaqI restriction endonuclease
      analysis in the case of IL-1beta. In each of the two groups (normotensives and
      hypertensives), genotype frequencies of all six markers occurred in Hardy
      Weinberg proportions. There were, however, no statistical differences in the
      allele and genotype frequencies of any of the six markers between the two groups
      of subjects: TGF-beta1(*)10C frequencies were 0.46 and 0.49 (chi(2)=0.61; 2 d.f.;
      P=0.74) and TGF-beta1(*)25C were 0.07 and 0.08 (chi(2)=0.61; 2 d.f.; P=0.74)
      amongst normotensives and hypertensives, respectively; p(IFN-gamma(*)A874) were
      0.41 in normotensives versus 0.46 in hypertensives (chi(2)=3.07; 2 d.f.; P=0.22);
      p(EGF (*)G61) were 0.51 versus 0.58 (chi(2)=1.76; 2 d.f.; P=0.41); p[IL-1beta
      (*)TaqI(+)] were 0.43 versus 0.36 (chi(2)=2.08; 2 d.f.; P=0.35); and p(TNF
      alpha(*)-308G) were 0.80 versus 0.85 (chi(2)=1.29; 2 d.f.; P=0.53). There was
      also no difference in distribution and frequencies of haplotypes constructed with
      combinations of TGF-beta1(*)10(T>C) and TGF-beta1(*)25(G>C) sites. However,
      although they do not reach statistical significance (which may be due to the
      relatively restricted number of subjects included in this study), the
      distribution differences (in normotensives and hypertensives) observed in the
      cases of EGF and TNF-alpha reflect trends that could be expected from a
      mechanistic explanation of the pathways that underlie the patho-physiology of
      hypertension.

PMID- 12009576
TI  - Role of p53 in the sensitization of tumor cells to apoptotic cell death.
AB  - Immunotherapy of cancer has always represented a very attractive fourth-modality
      therapeutic approach. Over the past few years, advances in the identification of
      tumor antigens have opened new perspectives and provided new opportunities for a
      more accurate immunotherapy of cancer. However, when applied to patients with
      established tumors, it rarely leads to an objective response. This is in part due
      to the fact that tumors evade host immunity at both the induction and effector
      phases. In this regard, several different functional defects in T-lymphocytes
      that infiltrate cancers have been reported. Indeed, lymphocytes of patients with
      advanced malignancies are hyporeactive and functionally compromised. Furthermore,
      it has become clear that immunotherapeutic and gene therapeutic approaches aimed
      at the induction of anti-tumor cytotoxic responses should consider the resistance
      of tumor cells to cytotoxic mechanisms. Thus, understanding of tumor escape
      mechanisms may be the key to a successful immunotherapy for cancer. How tumors
      escape immunological destruction following the acquisition of resistance to cell
      death and the potential role the tumor suppressor p53 protein in
      immunosensitization of tumor cells will be discussed.

PMID- 12009577
TI  - Immune recognition of cyclin B1 as a tumor antigen is a result of its
      overexpression in human tumors that is caused by non-functional p53.
AB  - Cyclin B1, which plays a key role in the control of cell cycle progression from
      G(2) through M phase, was recently identified by us as a tumor antigen recognized
      by human T-cells. To understand what makes this normal molecule antigenic, we
      compared its expression in malignant versus normal cells. Immunohistology showed
      overexpression of cyclin B1 protein in tumors compared to surrounding normal
      tissue and localization in the cytoplasm rather than the nucleus. Cyclin B1 is
      overexpressed at protein and mRNA level in many tumor cell lines including
      breast, lung, colorectal carcinoma, lymphoma and leukemia. While overexpressed in
      tumor cells at all stages of the cell cycle, its expression still peaks at G(2)/M
      phase, as it does in normal cells. We compared cyclin B1 expression in two cell
      clones derived from the same colorectal tumor cell line, one wild type for p53
      (HCT116p53(+/+)) and one with deleted p53 (HCT116p53(-/-)). HCT116p53(+/+) cells
      had undetectable (normal) level of cyclin B1 protein, while HCT116p53(-/-) cells
      showed overexpression. When reconstituted with p53, HCT116p53(-/-) cells reverted
      to normal cyclin B1 expression. We conclude that p53 plays an important role in
      cyclin B1 regulation and that tumors with mutated p53 will be good candidates for
      cyclin B1 based immunotherapy.

PMID- 12009578
TI  - Nitric oxide as a regulatory and effector molecule in the immune system.
AB  - Nitric oxide (NO) as a small ubiquitous molecule influencing a great variety of
      biological processes in the organism. Within the immune system, increased levels
      of NO were observed in various immunopathological situations, inflammatory
      reactions and during the response to transplantation and tumour antigens. It
      appears that NO can influence various facets of immune response. We studied
      involvement and the role of NO in immune response to skin allograft in mice. The
      production of NO at the site of graft rejection correlated well with the kinetic
      of rejection reaction and with the fate of the allograft. Graft infiltrating
      macrophages were identified as a principal cell population producing NO and the
      production of NO by macrophages was dependent on the presence of activated CD4(+)
      T cells. Survival of skin allografts was significantly prolonged by the treatment
      of graft recipients with 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a
      specific inhibitor of inducible NO synthase (iNOS). These results suggest a role
      for NO as the effector cytotoxic molecule involved in the graft rejection.
      Experiments in vitro demonstrated that NO, in addition to its effector function,
      acts as a modulator of cytokine production. Spleen cells stimulated with
      alloantigens in the presence of AMT or S-ethylisothiourea (EIT), an another
      selective iNOS inhibitor, produced considerably more interleukin (IL)-4 and IL-10
      than the cells stimulated in the absence of iNOS inhibitors. The production of
      Th1 cytokines IL-2 and interferon (IFN)-gamma was not enhanced by the inhibition
      of NO synthesis. The results altogether show that NO can act in transplantation
      reactions as an immunomodulator on cytokine production level and as an effector
      molecule involved in the graft destruction.

PMID- 12009579
TI  - The immunological synapse.
AB  - The immunological synapse plays a central role in organising the immune system.
      Through their synaptic activity both T and B cells usually, but not always,
      acquire the information that critically determines the level and nature of the
      responses that they make. For T cells much of that information comes from
      epicrine and paracrine cell-cell interactions in the cluster that forms around a
      dendritic cell. These interactions are being dissected by experiments in which
      two populations of TCR-transgenic T cells are combined in vivo. Another important
      aspect of synaptic activity is the way in which different levels of expression of
      MHC class II molecules influence Th1/Th2 balance. In exploring this form of
      control we are learning something of general importance about cis-regulation.

PMID- 12009580
TI  - 100 years ago: Ullmann's pioneering operation--autotransplantation of the kidney.

PMID- 12009582
TI  - Organ transplant in Brazil.

PMID- 12009583
TI  - Survival rate of graft and patient transplanted with cadaveric organs in the new
      transplant organization model of the state of Sao Paulo, Brazil: a multicentric
      analysis.

PMID- 12009584
TI  - Notifying potential donors: perspective of help from the intra-hospital
      transplantation committee.

PMID- 12009585
TI  - Academic community response to the Brazilian legislation for organ donation.

PMID- 12009586
TI  - Knowledge of organ donation among one group of Brazilian professors of medicine.

PMID- 12009587
TI  - Outcome of 605 consecutive living donor nephrectomies through an anterior
      subcostal retroperitoneal approach.

PMID- 12009588
TI  - Multiorgan donation in an organ procurement organization: evaluation of the
      causes of nondonation.

PMID- 12009589
TI  - The role of the psychologist on the pediatric renal transplant team.

PMID- 12009590
TI  - Brazilian's attitudes toward organ donation and transplantation.

PMID- 12009591
TI  - Comparative study of HLA-DR typing by serology and sequence-specific primer
      analysis in a genetically highly diverse population of kidney transplant
      recipients.

PMID- 12009592
TI  - Influence of chronic hepatitis C virus infection on lymphocyte phenotype in renal
      transplant recipients.

PMID- 12009593
TI  - Monitoring of soluble HLA class I in liver transplant recipients: correlation
      with transplant-related complications.

PMID- 12009594
TI  - Differentially expressed genes in cardiac transplant biopsies and in mixed
      lymphocyte culture.

PMID- 12009595
TI  - CD27 but not CD70 and 4-1BB intragraft gene expression is a risk factor for acute
      cardiac allograft rejection in humans.

PMID- 12009596
TI  - Granzyme B, FAS-ligand and perforin expression during acute cellular rejection
      episodes after kidney transplantation: comparison between blood and renal
      aspirates.

PMID- 12009597
TI  - Differential expression of cytokines, growth factors, and alpha-smooth muscle
      actin in renal allograft biopsies.

PMID- 12009598
TI  - Detection and clinical significance of lymphocytotoxic antibodies following renal
      transplantation.

PMID- 12009599
TI  - Endothelin-1 plasma levels in cyclosporine-treated stable renal transplant
      patients.

PMID- 12009600
TI  - Liver function tests in mycophenolate mofetil-treated hepatitis C virus-positive
      kidney allograft recipients.

PMID- 12009601
TI  - Mycophenolate mofetil in the treatment of chronic rejection in renal
      transplantation: 3-year follow-up.

PMID- 12009602
TI  - Five hundred transplants in 500 consecutive days.

PMID- 12009603
TI  - Toxoplasmosis transmitted via kidney allograft: case report and review.

PMID- 12009604
TI  - Protocol biopsies in renal transplant patients: three-years' follow-up.

PMID- 12009605
TI  - Unusual manifestations of leishmaniasis in renal transplant.

PMID- 12009606
TI  - Cutaneous leishmaniasis in kidney transplant recipient.

PMID- 12009607
TI  - Adverse effects of pregnancy on renal allograft function.

PMID- 12009608
TI  - Acute rejection is a risk factor for long-term survival in a single-center
      analysis of 1544 renal transplants.

PMID- 12009609
TI  - Angioplasty with stent is the preferred therapy for posttransplant renal artery
      stenosis.

PMID- 12009610
TI  - Biliary tract complications after orthotopic liver transplantation in adult
      patients.

PMID- 12009611
TI  - Liver transplantation using "refused grafts": analysis of initial function and
      survival.

PMID- 12009612
TI  - Early diagnosis of small bowel allografts rejection by Doppler ultrasound
      fluxometry.

PMID- 12009613
TI  - Effect of the inclusion of ruthenium red in three preservation solutions on the
      viability of freshly isolated and cold-stored rat pancreatic islets.

PMID- 12009614
TI  - Reconstruction of bone defects in the maxilla and mandibula through the use of
      frozen human bone.

PMID- 12009615
TI  - Organ transplantation in Poland.

PMID- 12009616
TI  - Early function of kidneys stored by continuous hypothermic pulsatile perfusion
      can be predicted using a new "viability index".

PMID- 12009617
TI  - Increased serum levels of markers of oxidative stress during kidney
      transplantation.

PMID- 12009618
TI  - Comparison of pretransplant serum alloreactivity estimated by immunoenzymatic
      assay (PRA-STAT) and lymphocytotoxic test in renal transplant recipients.

PMID- 12009619
TI  - Psychological evaluation of living kidney donors--the Polish experience.

PMID- 12009620
TI  - Use of daclizumab in the immunosuppression of high-risk kidney and
      kidney/pancreas recipients: Warsaw Transplantation Center experience.

PMID- 12009621
TI  - Mycophenolate mofetil in renal graft recipients with increased immune risk of
      graft loss.

PMID- 12009622
TI  - Cyclosporine blood concentration at 2 hours (C(2)) from drug ingestion as the
      best single indicator of adequate cyclosporine immunosuppression in renal
      allograft recipients--a four-year follow-up.

PMID- 12009623
TI  - Results of renal transplantation with different immunosuppressive regimens.

PMID- 12009624
TI  - Steroid withdrawal after renal transplantation--risks and benefits.

PMID- 12009625
TI  - Elevated serum immunoglobulins after steroid withdrawal in renal allograft
      recipients.

PMID- 12009626
TI  - Mycophenolate mofetil reduces graft loss due to chronic allograft nephropaty.

PMID- 12009627
TI  - Cyclosporine A-related hemolytic uremic syndrome after living renal
      transplantation-case report.

PMID- 12009628
TI  - Study on efficacy of influenza vaccination in renal allograft recipients.

PMID- 12009629
TI  - Total homocysteine as a risk factor for vascular disease in renal transplant
      recipients.

PMID- 12009630
TI  - Aluminium and beta-2-microglobulin in kidney transplant recipients.

PMID- 12009631
TI  - Low-stage renal carcinoma of the native kidneys in renal transplant recipients.

PMID- 12009632
TI  - Regulators of fibrynolysis in plasma of kidney transplant recipients.

PMID- 12009633
TI  - The significance of anti-HLA antibody presence in children who lost the
      transplanted kidney due to vascular thrombosis.

PMID- 12009634
TI  - Correlations between new markers of bone formation versus bone resorption in
      kidney transplant recipients.

PMID- 12009635
TI  - Parathyroid gland sonography in relation to markers of bone metabolism in kidney
      transplant recipients.

PMID- 12009636
TI  - Thyroid gland function in patients after renal transplantation.

PMID- 12009637
TI  - Endogenous neurotoxine-quinolinic acid is increased in renal allograft
      recipients.

PMID- 12009638
TI  - Improved autonomic function after kidney transplantation.

PMID- 12009639
TI  - Long-term results of kidney transplantation in recipients with atherosclerotic
      iliac arteries.

PMID- 12009640
TI  - Harvesting of liver segments II to III from living related donors for liver
      transplantation: own experience.

PMID- 12009641
TI  - Correlation between the function of transplanted liver and the quality of
      procured organ.

PMID- 12009642
TI  - Biochemical function of the donor liver in living related liver transplantation.

PMID- 12009643
TI  - Underutilization of potential cadaveric liver donors.

PMID- 12009644
TI  - Liver transplantation: comparison of the classical orthotopic and piggyback
      techniques.

PMID- 12009645
TI  - Toxic liver injury of transplanted liver: a case report of a 15-year-old boy.

PMID- 12009646
TI  - Liver transplantation in patients with Budd-Chiari syndrome.

PMID- 12009647
TI  - Liver transplantation in patients with hepatic failure.

PMID- 12009648
TI  - TIPS: a therapy to prevent variceal rebleeding in patients listed for liver
      transplantation.

PMID- 12009649
TI  - Liver retransplantation: indications and results.

PMID- 12009650
TI  - Presence of IgG anti-HLA antibodies in fourteen patients after cryopreserved
      allogenic heart valve implantation.

PMID- 12009651
TI  - Myocarditis complicated by cardiopulmonary shock, treated with extracorporeal
      assist device and heart transplantation.

PMID- 12009652
TI  - Effects of encapsulation on in vitro function of cryopreserved rat islets.

PMID- 12009653
TI  - Monitoring of pancreatic islets transplanted to colon mesentery.

PMID- 12009654
TI  - Biochemical and morphological changes in pancreas stored under hypothermic
      conditions.

PMID- 12009655
TI  - Survival of islet allografts under kidney capsule in the recipient preconditioned
      with or without myeloablation and treated with UVB-irradiated donor bone marrow
      infusion.

PMID- 12009656
TI  - In vitro activation of mice splenocytes by free and encapsulated rat islets and
      by components of capsular wall.

PMID- 12009657
TI  - Surgical complications observed in simultaneous pancreas-kidney transplantation:
      thirteen years of experience of one center.

PMID- 12009658
TI  - Posttransplant adoptive immunotherapy with interleukin-2 in children suffering
      from neuroectodermal tumors with poor prognosis.

PMID- 12009659
TI  - HLA typing for donor-recipient matching in unrelated donor hematopotetic stem
      cell transplantation.

PMID- 12009660
TI  - Human herpesvirus-6 and human herpesvirus-8 seroprevalence in kidney transplant
      recipients.

PMID- 12009661
TI  - Screening evaluation of oral cavity microorganisms in dialyzed and kidney
      allograft recipients under chronic immunosuppression.

PMID- 12009662
TI  - Tuberculosis in patients after renal transplantation remains still a clinical
      problem.

PMID- 12009663
TI  - Repopulation of donor heart with recipient bone marrow-derived dendritic cells
      does not prevent acute rejection.

PMID- 12009664
TI  - The T-cell apoptosis in the early period after renal allograft transplantation.

PMID- 12009665
TI  - Extracellular matrix composition and cellular mechanisms of transplant
      vasculopathy in rat aortic allografts.

PMID- 12009666
TI  - Flow cytometry crossmatch in living donor renal transplantation.

PMID- 12009667
TI  - Generation of H(2)O(2) prevents Fc receptor-mediated changes in redox potential,
      reducing beta integrin avidity and natural killer cell adhesion to porcine
      endothelium.

PMID- 12009668
TI  - Influence of Kupffer cells on the early phase of liver reperfusion.

PMID- 12009669
TI  - CsA does not inhibit alloantigen presentation by skin veiled (dendritic) cells.

PMID- 12009670
TI  - Donor DNA from rejecting organ and tissue grafts can be detected in recipient
      tissues.

PMID- 12009671
TI  - Bacterial infection of human skin allograft mimics the rejection process.

PMID- 12009672
TI  - Autologous transplanted hepatocytes: depletion of recipient leukocytes prevents
      in vivo lysis.

PMID- 12009673
TI  - Bone allograft harvesting following multiorgan procurement.

PMID- 12009674
TI  - Estimation of graft arteriosclerosis after allogeneic fresh and cryopreserved
      aortic transplantation in the rat.

PMID- 12009675
TI  - Immune response after cryopreserved aortic allograft replacement for major
      vascular infection.

PMID- 12009676
TI  - Role of native nephrectomy in renal transplant recipients.

PMID- 12009677
TI  - Retroperitoneoscopic living donor nephrectomy without gas insufflation: the five
      year Hamamatsu University experience.

PMID- 12009678
TI  - Prostate cancer in renal transplant recipients.

PMID- 12009679
TI  - Medical versus surgical management of atherosclerotic renal artery stenosis.

PMID- 12009680
TI  - Renal transplantation in children with malformations of the urinary tract.

PMID- 12009681
TI  - Hand-assisted laparoscopic donor nephrectomy for morbidly obese patients.

PMID- 12009682
TI  - USTVS survey of laporoscopic donor nephrectomy.

PMID- 12009683
TI  - Immunohistochemical study of experimental acute cellular rejection.

PMID- 12009684
TI  - Mechanism of norepinephrine-mediated inhibition of human NK cytotoxic functions:
      inhibition of cytokine secretion, target binding, and programming for
      cytotoxicity.
AB  - Norepinephrine (NE) has been shown to inhibit human peripheral blood-derived
      natural-killer (NK) cell cytotoxicity (NKCC) in vitro. We demonstrate in this
      study that NE not only inhibits IL-2-activated NKCC but antibody-dependent
      cellular cytotoxicity (ADCC) as well. NK cytotoxicity by purified NK cells
      against K562 (NKCC) and against Raji cells (ADCC) were inhibited by NE (1-100
      microM) by more than 50% in a 4-h (51)Cr release assay. The mechanism underlying
      the inhibition has been examined. NK cytotoxicity is dependent on target
      recognition and formation of NK-target conjugates, and activation by IL-2 is
      dependent on the secretion of cytokines (such as TNF-alpha) by NK cells. We
      hypothesized that the inhibition of NK functions by NE may be due to disruption
      of NK-target conjugation, blocking programming for lysis, and/or inhibition of
      cytokine secretion. Pretreatment of human peripheral blood mononuclear cells
      (PBMC) with NE for 15 min significantly reduced the binding to K562 cells by
      CD16(+) NK lymphocytes. In the presence of K562 cells, NE down-regulated the
      expression of CD16 (FcgammaRIII) by human PBMC, an NK cell receptor responsible
      and necessary for ADCC and cytokine secretion. We also demonstrate that NE
      inhibited the IL-2-mediated up-regulation of the activation marker CD69. At
      concentrations of 10(-6) to 10(-5) M, NE inhibited TNF-alpha, IFN-gamma, and GM
      CSF secretion by NK cells, which are essential for IL-2-driven NK maturation and
      functions. In addition, using single-cell analysis, NE pretreatment of
      lymphocytes reduced the frequency of killer cells in the NK-K562 conjugate
      population in a concentration-dependent manner, indicating an inhibition of the
      programming for lysis by NK cells. In summary, these data demonstrate that NE
      induced inhibition of NK cytotoxicity is manifested at multiple levels, including
      a modification of NK cell receptor ligation to target cells, blockade of NK
      cytokine secretion necessary for NK maturation and differentiation, and
      inhibition of the target-induced activation of the cytotoxic mechanism(s) in NK
      cells. Thus, sympathetic activation, as often induced experimentally, may
      profoundly impair natural cellular immunity through varied measurable pathways.

PMID- 12009685
TI  - Age-related changes in noradrenergic sympathetic innervation of the rat spleen is
      strain dependent.
AB  - Previous findings from our laboratory revealed an age-related decline in
      noradrenergic (NA) sympathetic innervation of the spleen in male Fischer 344
      (F344) rats. The purpose of this study was to determine whether other rat strains
      also progressively lose NA sympathetic nerves in the aging spleen. Sympathetic
      innervation of spleens from 3- and 21-month-old male F344, Brown Norway (BN), BN
      X F344 (BNF(1)), and Lewis rats was examined using fluorescence histochemistry to
      localize catecholamines combined with morphometric analysis and using high
      performance liquid chromatography with electrochemical detection for measuring
      norepinephrine (NE). Neurochemistry revealed a significant age-related decline in
      NE concentrations in spleens from F344 and Lewis rats. In contrast, there was no
      effect of age on splenic NE concentrations in BN or BNF(1) rats. Consistent with
      neurochemical analysis, fluorescence histochemistry revealed a striking decline
      in NA innervation of spleens from old F344 and Lewis rats not observed in the
      other two strains. However, in BN and BNF(1) rats, nerve fibers were diminished
      in distal portions of the spleen but not in the hilar regions. Morphometric
      analysis confirmed neurochemical and histological findings, revealing
      approximately 65-70% loss in NA nerve density in spleens from F344 and Lewis
      rats. These findings indicate that age-related changes in sympathetic innervation
      of the rat spleen are strain-dependent. Whether the loss of sympathetic nerves in
      spleens from F344 and Lewis rats is associated with age-related changes in the
      splenic microenvironment remains to be determined. The functional significance of
      altered sympathetic innervation of the spleen with advancing age is discussed.

PMID- 12009686
TI  - Temporal stability of acute stress-induced changes in leukocyte subsets and
      cellular adhesion molecules in older adults.
AB  - This study investigated the temporal stability of enumerative immune and
      catecholamine responses to acute psychosocial stress in 67 Alzheimer's caregivers
      ages 56-82 years (45 women and 22 men) who were required to prepare and deliver
      two 3-min speeches on three occasions at 2-week and 6-week intervals. All
      leukocyte subsets and adhesion molecules (CD62L and CD11a) changed significantly
      from rest to postspeak at each of the three testing sessions (p's <.0005).
      Responses showed moderate to high temporal stability across baseline and absolute
      task values (r's =.65-.96). Reliability was predictably lower for both forms of
      change scores (r's = -.16-.64). The level of temporal stability achieved is
      comparable to that seen previously in younger adults, indicating that acute
      psychosocial stress produces reliable changes in circulating leukocytes and cell
      adhesion molecules in older adults.

PMID- 12009687
TI  - Cyclic estradiol treatment enhances the effects of interleukin-1beta on food
      intake in female rats.
AB  - Proinflammatory cytokines elicit behavioral and physiological responses that
      include decreased food intake, fever, and a general disinterest in usual
      activities. Ovarian hormones modulate immune system activity and responsiveness
      to cytokines in female mammals, suggesting that sex differences in immune
      function may be influenced by gonadal steroids. In this experiment, female adult
      rats were ovariectomized and given two daily subcutaneous injections of 5.0 or
      20.0 microg of estradiol benzoate or the oil vehicle 3 weeks after surgery.
      Following 2 days of hormone treatment, animals received ip injections of
      interleukin-1beta (IL-1beta) or saline 1 h before light offset. Food and water
      intake was measured 2 h after light offset. The results indicate that a cyclic
      pattern of estradiol treatment enhances the anorectic effect of IL-1beta and
      suggest that responses to immune system activation are influenced by estradiol.

PMID- 12009688
TI  - Endocrine and cytokine responses to acute psychological stress in multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous
      system. An impaired hypothalamopituitary axis and stress reactivity have
      extensively been discussed without convincing experimental evidence. We choose a
      standardized acute psychological stressor to determine whether MS patients show
      altered endocrine and immune responses to stress. In 35 relapsing-remitting MS
      patients we found elevated baseline levels for catecholamines, prolactin, and IL
      6 compared to 15 healthy controls. All neuroendocrine parameters declined during
      the stress intervention in MS as well as in stress-exposed controls. But only
      prolactin showed a significantly larger decline in stressed MS patients versus
      controls. During exposure to the stress we found no significant changes in serum
      levels of IL-6, IL-6 receptor, or TNF-alpha in either MS patients or controls
      after stimulation of a whole blood culture. An altered neural immune signaling in
      relapsing-remitting MS patients during acute experimental stress could not be
      proven for the parameters analyzed.

PMID- 12009689
TI  - Continuous measurement of glucose utilization in heart myoblasts.
AB  - Understanding quantitative aspects of cell energy metabolism and how it is
      influenced by environment is central to biology, medicine, and biotechnology.
      Most methods used for measuring metabolic fluxes associated with energy
      metabolism require considerable personnel effort or high maintenance
      instrumentation. The microphysiometer is a commercially available instrument that
      measures acid extrusion rates, which are commonly used for drug screening. With
      the addition of oxygen sensors, the instrument can also be used to measure cell
      oxygen consumption rates and thereby calculate glycolytic fluxes. In the work
      described here, oxygen consumption and acid extrusion rates were used to measure
      glucose utilization by the H9c2 rat heart myoblast cell line and these results
      are compared with fluxes measured with a radiometric assay. Both assays were used
      to investigate changes in H9c2 energy metabolism due to cell stimulation with
      carbachol and insulin. The results demonstrate the utility of the
      microphysiometer method for measuring both transient and sustained changes in
      partitioning of glucose utilization between glycolysis and oxidation in live
      cells.

PMID- 12009690
TI  - Labeling of antibodies by in situ modification of thiol groups generated from
      selenol-catalyzed reduction of native disulfide bonds.
AB  - A new method for labeling antibodies which involves selenol-catalyzed reduction
      of native disulfide bonds in antibodies to generate thiol groups, which then are
      labeled using thiol-reactive reagents, is described. The reduction and labeling
      steps of this rapid procedure are carried out in one vessel, without requiring
      any separation step to remove the reductant before labeling. It results in a
      quantitative and homogenous incorporation of about seven labeled groups per
      antibody molecule in less than 5 min. All reagents used are commercially
      available-selenocystamine (catalyst precursor), dithiothreitol or tris(2
      carboxyethyl)phosphine (reductant), and thiol-reactive labeling reagents such as
      biotin-poly(ethylene oxide)-maleimide. This method is broadly applicable for
      labeling proteins such as immunoglobulins with reducible disulfide bonds, whose
      reduction and labeling does not result in a significant loss of activity.
      Biotinylated murine antibodies (anti-phosphotyrosine and anti-EGF receptor)
      prepared by this reduced-disulfide labeling method perform comparably or better
      than amino-group biotinylated antibodies in applications such as enzyme-linked
      immunosorbent assay, immunohistochemistry, and immunoprecipitation. This reduced
      disulfide labeling method is superior to amino-group labeling methods because it
      is not inhibited by the presence of amines in solution, as demonstrated by the
      biotinylation of an antibody in a hybridoma culture supernatant containing amino
      acids and serum proteins.

PMID- 12009691
TI  - Activation of cellulose membranes with 1,1'-carbonyldiimidazole or 1-cyano-4
      dimethylaminopyridinium tetrafluoroborate as a basis for the development of
      immunosensors.
AB  - Methods for the activation of a cellulose dialysis membrane for immunosensor
      applications have been developed. For activation two reagents, 1,1'
      carbonyldiimidazole (CDI) and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate
      (CDAP), were compared with respect to the coupling efficiency for glucose oxidase
      (GOx) and 1,8-diamino-2,6-dioxaoctane. The maximum level of activation was 2.4
      micromol cm(-2) for CDI and 0.2 micromol cm(-2) for CDAP activation. We observed
      1.5 microg cm(-2) and 0.4 x 10(-4) U cm(-2) GOx with CDI-activated membranes
      whereas 1.7 microg cm(-2) and 7.2 x 10(-4) U cm(-2) GOx were observed with CDAP
      activated membranes. With 1,8-diamino-2,6-dioxaoctane amino group densities of
      0.165 and 0.09 micromol cm(-2) were observed via CDI and CDAP activation,
      respectively. An amino-modified membrane was used for coupling a ligand
      (pentapeptide) and an immunoenzymometric assay for hemoglobin A1c was carried
      out.

PMID- 12009692
TI  - A multiparameter screening assay to assess the cytokine-induced expression of
      endothelial cell adhesion molecules.
AB  - Compounds which inhibit endothelial cell inflammatory responses are believed to
      be of therapeutic value. The cell adhesion molecules E-selectin, ICAM-1, and VCAM
      1 play important roles in inflammatory reactions by mediating leukocyte
      endothelial interactions. To identify compounds which inhibit the expression of
      these adhesion molecules following cytokine stimulation we developed an assay
      which measures E-selectin, ICAM-1, and VCAM-1 in the same experiment. For this,
      we have taken advantage of the technology of time-resolved fluorimetry, which
      allows detection of several parameters in parallel, employing anti-E-selectin
      antibody labeled with europium, and anti-ICAM-1 and anti-VCAM-1 labeled with
      samarium and terbium, respectively. These antibodies were used to detect the
      respective antigens in human endothelial cells stimulated with TNFalpha or IL
      1beta. In cross-competition assays these antibodies were found to bind
      specifically to TNF- or IL-1-stimulated cells. This assay, in which three
      parameters are measured in the same experiment, proved to be robust with signal
      to noise ratios of 25-35 for E-Selectin, 4-8 for ICAM-1, and 3-9 for VCAM-1. The
      assay proved to be reproducible in high-throughput screening. The experience with
      this assay demonstrates that multiple parameters can be measured in an enzyme
      linked immunosorbent assay-type assay on cells by using time-resolved
      fluorimetry. The possibility of obtaining several parameters from one experiment
      is feasible under high-throughput screening conditions and is of interest for
      other experimental setups in which the simultaneous measurement of several
      parameters is desired.

PMID- 12009693
TI  - Homogenous assays for Escherichia coli DnaB-stimulated DnaG primase and DnaB
      helicase and their use in screening for chemical inhibitors.
AB  - Escherichia coli DnaG primase is a single-stranded DNA-dependent RNA polymerase.
      Primase catalyzes the synthesis of a short RNA primer to initiate DNA replication
      at the origin and to initiate Okazaki fragment synthesis for synthesis of the
      lagging strand. Primase activity is greatly stimulated through its interaction
      with DnaB helicase. Here we report a 96-well homogeneous scintillation proximity
      assay (SPA) for the study of DnaB-stimulated E. coli primase activity and the
      identification of E. coli primase inhibitors. The assay uses an adaptation of the
      general priming reaction by employing DnaG primase, DnaB helicase, and
      ribonucleotidetriphosphates (incorporation of [(3)H]CTP) for in vitro primer
      synthesis on single-stranded oligonucleotide and M13mp18 DNA templates. The
      primase product is captured by polyvinyl toluene-polyethyleneimine-coated SPA
      beads and quantified by counting by beta-scintography. In the absence of helicase
      as a cofactor, primer synthesis is reduced by 85%. The primase assay was used for
      screening libraries of compounds previously identified as possessing
      antimicrobial activities. Primase inhibitory compounds were then classified as
      direct primase inhibitors or mixed primase/helicase inhibitors by further
      evaluation in a specific assay for DnaB helicase activity. By this approach,
      specific primase inhibitors could be identified.

PMID- 12009694
TI  - Identification of polysaccharide binding proteins by affinity electrophoresis in
      inhomogeneous polyacrylamide gels and subsequent SDS-PAGE/matrix-assisted laser
      desorption ionization-time of flight analysis.
AB  - A procedure that allows the identification of polysaccharide binding polypeptides
      is described. The method can be applied to proteins whose enzymatic activity is
      either unknown or cannot be identified unambiguously by activity-staining
      procedures and it has been used for very complex protein mixtures, such as crude
      extracts of plant organs. The procedure consists of three steps. First, an
      affinity polyacrylamide gel electrophoresis using an inhomogeneous polyacrylamide
      slab gel composed of two triangular parts, an upper gel lacking the ligand and a
      lower triangular gel containing an immobilized ligand, is performed. Proteins
      that interact with the ligand form bands that deviate from those of nonbinding
      proteins and can be detected by protein staining (or, if possible, by activity
      staining). Second, the bands containing the interacting proteins are excised,
      denatured, and subjected to SDS-PAGE using a slab gel. In the resulting protein
      pattern the target proteins cover most of the length of the gel piece applied to
      the SDS gel, whereas contaminating proteins appear as spots or narrow bands.
      Suitable regions of the target protein bands are selected for tryptic digestion.
      Third, the resulting peptides are analyzed by matrix-assisted laser desorption
      ionization-mass spectrometry followed by database research.

PMID- 12009695
TI  - Enzyme assays by fluorescence polarization in the presence of polyarginine: study
      of kinase, phosphatase, and protease reactions.
AB  - We have previously reported that the kinase catalyzed conversion of fluorescently
      labeled phosphate acceptor peptides to the corresponding phosphopeptides can be
      conveniently followed by measuring the fluorescence polarization signal in the
      presence of polyarginine. In the present work, we demonstrate that the method can
      be used for other enzymes besides kinases, such as phosphatases and proteases. By
      adjustment of the ionic strength of the buffer it is possible to use this method
      in cases where both the substrate and the enzymatic product are highly negatively
      charged. All of these enzymatic transformations can be followed in real time, by
      performing the reactions in the presence of polyarginine and continuously
      measuring the fluorescence polarization signal. Polyarginine was found to have no
      effect on the rate of enzymatic conversion of the protease studied (cathepsin G),
      but its presence decreased the observed rate of phosphorylation by protein kinase
      A, presumably by decreasing the concentration of free ATP in the reaction
      solution. Leukocyte antigen related phosphatase catalyzed dephosphorylation
      reactions were faster in the presence of polyarginine. For all three enzymes, the
      reaction rates in the presence of polyarginine were found to be sensitive to the
      presence of known enzyme inhibitors, but the IC(50) values of the kinase
      inhibitors H-89 and PKI were higher in the presence than in the absence of
      polyarginine.

PMID- 12009696
TI  - Mutation detection in KRAS Exon 1 by constant denaturant capillary
      electrophoresis in 96 parallel capillaries.
AB  - Mutations in KRAS exon 1 oncogene are frequently found in colon carcinomas. A
      correlation between the mutated KRAS and the prognosis and outcome of treatment
      of colon cancer patients was reported in the literature. The object of our work
      was to establish a high-throughput method with high sensitivity to enable
      screening of tumor mutation status of KRAS exon 1 in large groups of colon cancer
      patients. KRAS exon 1 sequences from DNA isolated from 191 sporadic colon cancers
      were PCR amplified using one primer labeled with fluorescein and a second primer
      extended by a GC-clamp. After PCR amplification samples were subjected to
      automated 96-array constant denaturant capillary electrophoresis using a modified
      MegaBACE 1000 sequencing instrument. Mutant samples were identified by
      characteristic peak patterns. The sensitivity of detection of a mutant allele in
      a background of the wild-type alleles was 0.3%. Using the 96-array instrument a
      typical screening of 191 samples for KRAS mutation status could be performed
      within 2 h. A KRAS exon 1 mutation was found in 66 of 191 (34.6%) of the samples.
      The 96-array constant denaturant capillary electrophoresis provides an
      opportunity for the high-sensitivity screening of large cancer populations for
      KRAS exon 1 mutations.

PMID- 12009697
TI  - Quality and quantity of DNA isolated from frozen urine in population-based
      research.
AB  - In several population-based studies in the past urine samples were collected and
      stored for future research. We set out to determine the reliability of using such
      samples for genotyping DNA markers in epidemiologic research. A source of DNA
      extracted from exfoliated nucleated cells in urine is provided by the DOM cohort,
      in which specimens were collected 15-25 years ago. We have examined the quality
      of the DNA in 48 of these samples by measuring the amount of DNA isolated and its
      ability to provide an adequate PCR template for amplicons of different lengths.
      MTHFR polymorphism was analyzed in 644 specimens to determine the inter- and
      intraobserver reproducibility. Although the DNA amount was variable, 26 to 89% of
      the samples, depending both on the length of the PCR amplicon and on PCR
      conditions, yielded a visible PCR product. The intra- and interobserver
      agreements were comparable (kappa 0.86 and 0.88, respectively). Our results
      demonstrate that frozen urine samples can be used for DNA typing studies in women
      after prolonged periods of storage, but with sometimes unpredictable results.
      Ultimately, the genotype success rate was 89.3%. Urine collection can be
      considered as a useful method of obtaining DNA in large cohort studies and other
      circumstances when blood samples cannot be obtained or have not been stored.

PMID- 12009698
TI  - Study on the polarographic catalytic wave of vitamin P in the presence of
      persulfate and its application.
AB  - The polarographic catalytic wave of vitamin P in the presence of persulfate was
      studied by linear potential scan polarography and cyclic voltammetry. Vitamin P
      yielded a single reduction wave in acidic aqueous solution, which was ascribed to
      a 2e(-), 2H(+) reduction of the carbonyl group in the C-4 position. Actually, the
      carbonyl group C=O first underwent a 1e(-), 1H(+) reduction to form a neutral
      free radical, and the further 1e(-), 1H(+) reduction of the free radical was
      simultaneous with its following chemical reactions. When S(2)O(2-)(8) was
      present, the free radical of vitamin P was oxidized by both S(2)O(2-)(8) and its
      reduction intermediate, the sulfate radical anion SO(*-)(4), to regenerate the
      original, which resulted in the production of a polarographic catalytic wave of
      vitamin P. Based on this catalytic wave, a novel method for the determination of
      vitamin P was proposed. In 0.02 M tartaric acid-sodium tartrate (pH 3.3) buffer
      containing 5.0 x 10(-3) M K(2)S(2)O(8), the peak potential of the catalytic wave
      was -1.42 V (vs SCE) and the peak current was rectilinear to the vitamin P
      concentration in the range of 8.0 x 10(-9)-1.0 x 10(-6) M (r = 0.9994, n = 13).
      The catalytic wave of 2.0 x 10(-7) M vitamin P enhanced the polarographic current
      70 times compared with the corresponding reduction wave. The detection limit was
      2.0 x 10(-9) M, and the relative standard deviation at the 2.0 x 10(-7) M level
      was 0.7% (n = 15). The proposed method was used for the determination of vitamin
      P content in the pharmaceutical preparation of tablets and the medicinal plant
      Sophora japonica L. without previous separation.

PMID- 12009699
TI  - The comparison of plasma deproteinization methods for the detection of low
      molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy.
AB  - Blood plasma is the major vehicle by which metabolites are transported around the
      body in mammalian species, and chemical analysis of plasma can provide a wealth
      of information relating to the biochemical status of an individual and is
      important for diagnostic purposes. However, plasma is very complex in
      physicochemical terms because it is composed of a range of organic and inorganic
      constituents with a wide range of molecular weights and chemical classes and this
      makes analysis non-trivial. It is now well established that high-resolution (1)H
      NMR spectroscopy of blood plasma provides useful qualitative and quantitative
      biochemical information relating to metabolic disorders. However, one of the
      problems encountered in NMR spectroscopic analysis of blood plasma is the
      extensive peak overlap or presence of broad macromolecule peaks in the (1)H NMR
      spectrum, which can severely limit the amount of obtainable information. Even
      with spectroscopic editing, information relating to low-molecular-weight (MW)
      metabolites is frequently lost. Therefore, the efficiency of a range of
      conventional protein removal methods, in combination with the use of one- and two
      dimensional NMR spectroscopic methods for evaluation, have been compared for the
      extraction of NMR-observable low-MW metabolites. It has been shown that these
      "deproteinization" methods vary considerably in recovery of low MW metabolites
      and a judicious choice is crucial for optimal extraction of a given analyte. The
      results presented here show that while ultrafiltration provides the "safest"
      method of plasma deproteinization, the signal-to-noise ratio of the resultant
      (1)H NMR spectra is poor. On the other hand, acetonitrile precipitation at
      physiological pH allows the detection of more low-MW metabolites and at higher
      concentrations than any other method and provides the further advantages of being
      a rapid and simple procedure.

PMID- 12009700
TI  - Detection of biotinylated proteins in polyacrylamide gels using an avidin
      fluorescein conjugate.
AB  - Biotinylated proteins are widely used as a molecular tool in biotechnological
      applications. In this paper, we demonstrated that biotinylated proteins after
      electrophoresis were detected directly in gels using an avidin-fluorescein
      conjugate with a fluorescence image analyzer. Upon analysis of the purified and
      chemically biotinylated protein, the sensitivity of this method was almost equal
      to that of silver staining. Chemically biotinylated proteins of Escherichia coli
      cell surfaces could also be specifically detected with our method. Furthermore,
      recombinant proteins fused with the biotin acceptor domain and biotinylated
      enzymatically in vivo were also detected in a lysate of E. coli specifically. The
      sensitivity and specificity of our method are high, and the procedure is simple.
      Therefore, our method would benefit detection of biotinylated proteins via gel
      electrophoresis and also various fields of study using avidin-biotin technology.

PMID- 12009701
TI  - Real-time monitoring of histamine released from rat basophilic leukemia (RBL-2H3)
      cells with a histamine microsensor using recombinant histamine oxidase.
AB  - To detect low levels of histamine, we developed a histamine microsensor using
      recombinant histamine oxidase. Histamine oxidase with a histidine tag was readily
      purified using a histidine affinity column. The enzyme showed higher catalytic
      activity on histamine than diamines (e.g., putrescine and cadaverine) or N(tau)
      methylhistamine. The sensor had three carbon film electrodes modified with osmium
      polyvinylpyridine-based gel containing horseradish peroxidase, histamine oxidase,
      and Ag. When a standard solution of histamine was aspirated at a flow rate of 2
      microl/min, the detected current was proportional to the histamine concentration
      and the lower detection limit was 11.3 nM. When rat basophilic leukemia cells (1
      x 10(6)) were stimulated by various concentrations of antigen (2, 20, and 200
      ng/ml), the histamine concentrations were 0.32, 2.7, and 1.3 microM,
      respectively, and 20 ng/ml of antigen was found to be the optimal concentration
      for the antigen-antibody reaction. In contrast, when thapsigargin, an inhibitor
      of Ca-ATPase in the endoplasmic reticulum, was added (50, 100, and 500 nM), the
      detected current increased with thapsigargin concentrations and the measured
      histamine concentrations were 28 nM, 1.3 microM, and 2.7 microM, respectively.
      These results indicate that the microsensor is useful for the analysis of
      histamine release from mast cells.

PMID- 12009702
TI  - Flow injection spectrophotometric determination of the antibiotic fosfomycin in
      pharmaceutical products and urine samples after on-line thermal-induced
      digestion.
AB  - A new flow injection (FI) method for the precise and rapid spectrophotometric
      determination of the antibiotic fosfomycin (FMC) in urine and pharmaceutical
      samples is described. The method is based on the on-line quantitative thermal
      induced digestion of the analyte prior to injection into the FI system. Ammonium
      persulfate was used as the oxidation reagent. The resulting orthophosphate ions
      were determined spectrophotometrically (lambda(max) = 690 nm) using the
      molybdenum blue approach. Chemical and FI variables that affected on-line
      oxidation were studied and optimized. The proposed method is very precise (s(r) =
      1.2% at 1.0 x 10(-4) mol L(-1) FMC, n = 12), offers a high sampling rate of 60 h(
      1), and allows for the determination of the analyte in the range 3.0 x 10(-6) to
      3.0 x 10(-4) mol L(-1) with a satisfactory 3sigma detection limit of 1.0 x 10(-6)
      mol L(-1). Application of the proposed method to urine and pharmaceutical samples
      yielded accurate results with percentage recoveries in the range 96.4-102.5%.

PMID- 12009703
TI  - Quantitative intercomparison of transmission electron microscopy, flow cytometry,
      and epifluorescence microscopy for nanometric particle analysis.
AB  - Nanometric biological particles such as viruses have received increased attention
      in a wide range of scientific fields. Evaluation of viral contributions to
      environmental processes and the use of viruses in medical applications such as
      gene therapy require viruses to be routinely and accurately enumerated. There are
      a variety of existing techniques for counting viruses, namely, plaque assays,
      transmission electron microscopy (TEM), epifluorescence microscopy (EFM), and
      flow cytometry (FCM); each has advantages and disadvantages. While there have
      been attempts to intercompare some of these techniques to determine the most
      effective means to count viruses, no previous study used a technique-independent
      standard for quantitative comparison of collection efficiency, accuracy, and
      precision. In this work, polystyrene nanospheres were used as standards for the
      intercomparison of performance characteristics for TEM, EFM, FCM, as well as a
      custom-built flow cytometer (the Single Nanometric Particle Enumerator, SNaPE).
      EFM and SNaPE exhibited the highest degree of accuracy and precision, with
      particle concentrations deviating < or =5% from true and relative errors less
      than half that of TEM, EFM and SNaPE are also significantly more time and cost
      efficient than TEM.

PMID- 12009704
TI  - A strategy for examining complex mixtures of deoxyoligonucleotides using ion-pair
      reverse-phase high-performance liquid chromatography, matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry, and informatics.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) and ion-pair-reverse-phase high-performance liquid chromatography
      (IP-RP HPLC) techniques were combined to determine the sequence identity of short
      single-stranded deoxyoligonucleotides. This methodology is demonstrated using a
      commercially available multiplex set of eight primer pairs. The primer pairs were
      separated and collected by IP-RP HPLC. Partial sequence information for IP-RP
      HPLC fractions was obtained from analyzing exonuclease digestion products by
      MALDI-TOF MS. IP-RP HPLC, MALDI-TOF MS, exonuclease digests, and a simple
      computational algorithm provide an integrated strategy for determining the
      sequence of short nucleic acid oligomers.

PMID- 12009705
TI  - In situ analysis of carboxyl and sulfhydryl groups of extracellular polymeric
      secretions by confocal laser scanning microscopy.

PMID- 12009706
TI  - One-tube protocol for single-cell reverse transcriptase-polymerase chain
      reaction.

PMID- 12009707
TI  - A highly stable covalent conjugated heparin biochip for heparin-protein
      interaction studies.

PMID- 12009709
TI  - Pregnant again after peripartum cardiomyopathy: to be or not to be?

PMID- 12009710
TI  - ARTS I -- the rapamycin eluting stent; ARTS II -- the rosy prophecy.

PMID- 12009711
TI  - Urate levels as a predictor of cardiac deaths: causal relation or mere
      association?

PMID- 12009712
TI  - Is C-reactive protein an additional, surrogate end-point for statin treatment?

PMID- 12009713
TI  - Alterations in oxygen consumption and sympathetic nervous activity in heart
      failure: independent or associated mechanisms?

PMID- 12009714
TI  - In-hospital management of syncope: the European perspective.

PMID- 12009715
TI  - A step further in inter-institutional agreement in interpretation of dobutamine
      stress echocardiograms.

PMID- 12009716
TI  - Towards prevention, and not just postponement, of atherosclerotic disease.

PMID- 12009717
TI  - Molecular and genetic aspects of cardiac fatty acid homeostasis in health and
      disease.

PMID- 12009718
TI  - Urate predicts subsequent cardiac death in stroke survivors.
AB  - AIMS: To test the hypothesis that urate predicts cardiac death after stroke
      independent of conventional risk factors of atherosclerosis, creatinine and
      diuretic use. METHODS AND RESULTS: Serum urate concentration was measured in an
      unselected cohort of 354 stroke survivors who were followed-up for a median of
      2.8 years. Cardiac death was the primary end-point. Urate was associated with a
      statistically significant threefold increase in relative risk of cardiac death
      even after adjustment for other conventional risk factors. In the subgroup of
      patients who were not on diuretics, raised urate was associated with a 12-fold
      significant increase in relative risk of cardiac death after adjusting for renal
      function and other conventional risk factors. A urate concentration of greater
      than 0.31 mmol. l(-1) was 78% sensitive at predicting cardiac death within 5
      years after stroke, but was only 54% specific. If urate exceeded 0.38 mmol. l(
      1), specificity of predicting cardiac death within 5 years after stroke was 88%.
      CONCLUSIONS: Elevated serum urate concentration may be used to stratify risk of
      future cardiac death after stroke. This appeared to be true even in stroke
      survivors who were not on diuretic therapy.

PMID- 12009719
TI  - Short-term effects of atorvastatin on C-reactive protein.
AB  - AIM: To study the short-term effect of atorvastatin on C-reactive protein (CRP)
      in patients with or at risk for coronary heart disease. METHODS AND RESULTS: One
      hundred and fifty-five randomly selected patients from the SWiss Intervention
      Trial for lowering CHolesterol (SWITCH) were assessed for high sensitivity CRP,
      total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides at
      baseline, and after 1 and 3 months of treatment with atorvastatin at various
      doses to reach pre-defined lipid target values. The median decrease of
      cholesterol was 28% after 1 month and 35% after 3 months. LDL-cholesterol was
      decreased by 37% and 45%, HDL-cholesterol was increased by 7% and 8%,
      respectively. Patients with a low CRP baseline concentration (lowest quartile
      <1.34 mg. l(-1)) displayed no significant change, whereas patients in the other
      quartiles showed a significant decrease, of 22% to 40% (P -value <0.05 to <0.001)
      at 1 month and of 32% to 36% after 3 months compared to baseline. The decrease in
      CRP lowering was thus fully established by 1 month and this response was
      independent of lipid and lipoprotein changes as well as atorvastatin doses.
      CONCLUSION: Atorvastatin significantly decreases CRP concentrations after 4 weeks
      of therapy. These results may be important with respect to the early benefit of
      statin therapy.

PMID- 12009720
TI  - Peak oxygen uptake is not determined by cardiac noradrenaline spillover in heart
      failure.
AB  - AIMS: We recently found that resting muscle sympathetic nerve activity is
      inversely related to peak oxygen uptake (VO(2) peak) in patients with heart
      failure, suggesting a peripheral neurogenic limit to exercise in heart failure.
      No such relationship was observed in healthy controls. To determine whether this
      observation is specific to sympathetic discharge to skeletal muscle, we tested
      the null hypothesis that VO(2) peak would not relate to resting cardiac
      noradrenaline spillover, which is also elevated in heart failure. METHODS AND
      RESULTS: We measured cardiac noradrenaline spillover at rest by a radiotracer
      technique and VO(2) peak, during cycle ergometry, by open circuit spirometry in
      49 heart failure patients (mean age 54.4+/-1.4 (SE)). There was a significant
      relationship between age and peak VO(2) (P=0.022). There was no significant
      relationship between cardiac noradrenaline spillover and either absolute or
      relative VO(2) peak (P=0.136), with age included in a multiple linear regression
      model, and none between cardiac noradrenaline spillover and the percent predicted
      VO2) peak achieved (P=0.34). CONCLUSIONS: Reduced exercise capacity in heart
      failure relates more closely to sympathetic traffic to skeletal muscle than to
      cardiac sympathetic outflow, as assessed by noradrenaline spillover. This finding
      lends further support to the concept of a predominantly peripheral neurogenic
      limit to exercise.

PMID- 12009721
TI  - A non-invasively determined surrogate of cardiac power ('circulatory power') at
      peak exercise is a powerful prognostic factor in chronic heart failure.
AB  - OBJECTIVES: This study was designed to assess the prognostic value of a new
      variable derived from a cardiopulmonary exercise test, the circulatory power, a
      surrogate of cardiac power, at peak exercise, in patients with chronic heart
      failure. BACKGROUND: Peak exercise cardiac power and stroke work are invasive
      parameters with recently proven prognostic value. It is unclear whether these
      variables have better prognostic value than peak oxygen uptake (VO(2)). METHODS:
      The study population comprised 175 patients with chronic heart failure (ejection
      fraction <45%) who underwent a cardiopulmonary exercise test. Circulatory power
      and circulatory stroke work were defined as the product of systolic arterial
      pressure and VO(2) and oxygen pulse, respectively. Prognostic value was assessed
      by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses.
      RESULTS: With a mean follow-up of 25+/-10 months, ejection fraction, heart rate,
      systolic arterial pressure, peak VO(2), VCO(2), the anaerobic threshold, minute
      ventilation, the ventilatory equivalents of oxygen and carbon dioxide, the half
      times of VO(2) and VCO(2) recoveries, and the circulatory stroke work and power
      predicted outcome. Multivariate analysis demonstrated that the peak circulatory
      power (chi-square=19.9, P<0.001) (but not peak circulatory stroke work) was the
      only variable predictive of prognosis. CONCLUSION: The prognostic value of
      cardiopulmonary exercise tests in heart failure patients can be improved by
      assessing a new variable, the circulatory power - a surrogate of cardiac power -
      at peak exercise.

PMID- 12009722
TI  - Prospective evaluation and outcome of patients admitted for syncope over a 1 year
      period.
AB  - AIMS: Syncope is a frequent and potentially dangerous symptom. The
      epidemiological data are based on series mainly collected 20 years ago in the
      U.S.A. and do not adequately assist in the management of patients admitted now
      for this symptom in Europe. METHODS AND RESULTS: To evaluate prospectively the
      epidemiological aspects and the management of the patients admitted in the
      emergency department of an adult university hospital for a 'verified' syncope,
      charts of all the patients consecutively admitted between June 1999 and June 2000
      were systematically reviewed by a member of the cardiology staff. Those with a
      loss of consciousness were selected and those with a definite syncope were
      included in the study group and followed until they were discharged from the
      hospital. Among the 37,475 patients who presented to the emergency department,
      454 (1.21%) had a definite syncope. For 296 it was the first episode and 169
      (mean age 43+/-23 years) were discharged straight away; 285 (mean age 66+/-19
      years; P<0.0001) were admitted to internal medicine (n=151), cardiology (n=65),
      neurology (n=44), endocrinology (n=14) and surgery (n=11) services. In 75.7% of
      all the patients a diagnosis was reported but it was inadequate to explain a
      syncopal episode in 56 cases (16.3%). Management differed by department: 36% of
      the patients had 'neurological' investigations mainly in internal medicine and
      neurology. Except in cardiology very few had 'cardiological' investigations
      particularly tilt test and electrophysiological studies (5%). CONCLUSION: Syncope
      is a frequent symptom but its cause often remains unknown partly due to
      inadequate management. Precise and simple guidelines are urgently needed.

PMID- 12009723
TI  - Refinements in stress echocardiographic techniques improve inter-institutional
      agreement in interpretation of dobutamine stress echocardiograms.
AB  - AIMS: To determine the degree of inter-institutional agreement in the assessment
      of dobutamine stress echocardiograms using modern stress echocardiographic
      technology in combination with standardized data acquisition and assessment
      criteria. METHOD AND RESULTS: Among six experienced institutions, 150 dobutamine
      stress echocardiograms (dobutamine up to 40 microg x kg(-1) min(-1) and atropine
      up to 1 mg) were performed on patients with suspected coronary artery disease
      using fundamental and harmonic imaging following a consistent digital acquisition
      protocol. Each dobutamine stress echocardiogram was assessed at every institution
      regarding endocardial visibility and left ventricular wall motion without
      knowledge of any other data using standardized reading criteria. No patients were
      excluded due to poor image quality or inadequate stress level. Coronary
      angiography was performed within 4 weeks. Coronary angiography demonstrated
      significant coronary artery disease (> or = 50% diameter stenosis) in 87
      patients. Using harmonic imaging an average of 5.2+/-0.9 institutions agreed on
      dobutamine stress echocardiogram results as being normal or abnormal (mean kappa
      0.55; 95% CI 0.50-0.60). Agreement was higher in patients with no (equal
      assessment of dobutamine stress echocardiogram results by 5.5+/-0.8 institutions)
      or three-vessel coronary artery disease (5.4+/- 0.8 institutions) and lower in
      one- or two- vessel disease (5.0+/-0.9 and 5.2+/-1.0 institutions, respectively;
      P=0.041). Disagreement on test results was greater in only minor wall motion
      abnormalities. Agreement on dobutamine stress echocardiogram results was lower
      using fundamental imaging (mean kappa 0.49; 95% CI 0.44-0.54; P<0.01 vs harmonic
      imaging). CONCLUSION: Modern echocardiographic technology in combination with
      standardized digital image processing and uniform reading criteria results in a
      higher inter-institutional agreement in the interpretation of dobutamine stress
      echocardiogram compared to historic reports.

PMID- 12009726
TI  - Stress response to cold in Trichinella species.
AB  - Trichinella-type larvae (L(1)) are found in the muscles of infected wild animals
      and domestic pigs and are the cause of trichinosis in man and other animals
      throughout the world. These parasites are exposed to low temperatures during
      their life cycle. On this premise, three Trichinella species of different types
      of habitat (the arctic T. nativa, the cosmopolitan T. spiralis, and the tropical
      T. nelsoni) were selected to examine the effect of a shift in temperature, from
      37 to 4 degrees C, on long-term survival. Evaluation was then made of whether
      these effects were related to differential protein synthesis and/or heat shock
      protein (Hsp) expression. Test samples at 0, 2, 4, or 8 h and 1, 5, or 9 days
      after the temperature shift were obtained and subjected to Hsp determination by
      Western blotting. Total protein changes were explored by SDS-PAGE followed by
      densitometric analysis of the gels. During the "acclimatization phase" (at 2, 4,
      and 8 h), a different total protein and a depressed Hsp expression pattern were
      shown in each Trichinella species. Following acclimatization, Hsp70, but not
      Hsp60 or Hsp90, markedly increased above control levels in the three species,
      indicating a role for this Hsp as a classic stress protein. The synthesis of a 50
      kDa Hsp was significantly induced in T. spiralis larvae, suggesting its potential
      function as a cold shock protein in this species.

PMID- 12009727
TI  - Improvement of rat liver function by energy repletion after the preservation
      period: implications for hepatic graft management.
AB  - We very recently showed (using a blood-free perfusion model) that cold
      preservation sensitized rat hepatocyte functions to rewarming ischemic injury and
      that the injury can be prevented by repleting high-energy adenylates in the liver
      by short-term oxygenated warm reperfusion. Here we investigated whether short
      term reperfusion after the preservation period can improve hepatic graft function
      in a blood reperfusion model. Eighteen-hour cold-preserved rat livers either
      untreated (Group A) or pretreated by 30-min oxygenated warm reperfusion after
      preservation (Group B) were subjected to 20-min ischemic rewarming and then
      reperfused with blood. Livers in Group B compared to Group A exhibited approx.
      three times increased bile production and bromosulfophthalein excretion, nearly 7
      fold decreased swelling, and 1.2-fold improved blood flow. These results suggest
      that repletion of the energy by short-term oxygenated reperfusion after prolonged
      preservation may improve markedly initial hepatic graft function.

PMID- 12009728
TI  - Glutathione synthesis during the rewarming of rat hepatocytes preserved in the
      University of Wisconsin solution.
AB  - In this study, we used isolated rat hepatocytes to investigate the effect of
      nucleoside content of the preserved cells on the ability to synthesize
      glutathione (GSH) during the rewarming process. We cold-stored hepatocytes in
      University of Wisconsin (UW) solution (72 h, 0 degrees C, N(2)) without
      nucleosides and with the addition of 5 mM adenosine or 10 mM ATP. After 72 h of
      cold storage, we determined the GSH synthesis rate and the ATP content of the
      cells. We found a GSH synthesis rate similar to that of freshly isolated
      hepatocytes only in the group of cells cold-stored with 10 mM ATP. When we tested
      the cellular ATP concentrations, we found that controls and preserved cells with
      10 mM ATP showed a similar value of ATP during the rewarming step. Our results
      suggested that the incorporation of ATP in the UW solution increased the ATP
      content and the rate of GSH synthesis of cold-stored hepatocytes during
      rewarming.

PMID- 12009746
TI  - The relationship between adolescent academic capability beliefs, parenting and
      school grades.
AB  - The purpose of this study was to examine the interplay between parenting,
      adolescent academic capability beliefs and school grades. First, we examined how
      aspects of parenting and adolescent's cognitive ability predicted adolescent
      academic capability beliefs and school grades at 6th grade, which, in turn,
      predicted adolescent school outcomes at 9th grade. Second, we examined how
      configurations of adolescents (based on cognitive ability, parental involvement,
      and capability beliefs) at 6th grade, related to their school grades at 9th
      grade. The sample included 641 German adolescents. The first set of analyses
      suggest that parents who demonstrated more warmth, engaged in more discussions
      concerning academic and intellectual matters with their adolescents, had higher
      school aspirations for their adolescents, and reported more interest/involvement
      in their adolescent's schooling, had adolescents with higher capability beliefs
      at 6th grade, and this, in turn, related to better school grades for adolescents
      at 9th grade. In the second set of analyses, results show that adolescents who
      were characterized by the configuration of having above average ability, parental
      school involvement and capability beliefs, received the best school grades. In
      contrast, adolescents who were characterized by below average ability, parental
      school involvement and capability beliefs, demonstrated the worst school
      performance.

PMID- 12009747
TI  - The role of personality, parents and peers in adolescents career exploration.
AB  - The role of individual characteristics, parental behaviours and peers for
      occupational exploration was examined in a sample of 192 German ninth graders (80
      girls, 112 boys) from middle-track schools. The adolescents completed
      questionnaires at two points of measurement which were 6 months apart. The
      results showed that individual characteristics which reflected an active and
      constructive approach to developmental demands were correlated with more intense
      occupational exploration. Child-centred parental behaviours were also correlated
      positively with information-seeking behaviours. Moreover, parental behaviours
      predicted change in exploration over the observed time period. Concerning the
      role of peers which was often neglected in career development theory, the results
      showed that frequent talks with peers about career-related issues were
      significantly associated with the intensity of information-seeking behaviours
      and, at the same time, predicted an intensification of occupational exploration
      during the following 6-month period. The findings suggest that it would be
      fruitful to consider more thoroughly the role of peers in future research on
      adolescents' career development.

PMID- 12009748
TI  - Achievement strategies at school: types and correlates.
AB  - In this study we made an effort to identify the kinds of strategies adolescents
      deploy in achievement context in an unselected sample of Swedish adolescents. The
      participants were 880 14-15-year-old comprehensive school students (399 boys and
      481 girls) from a middle-sized town in central Sweden. Six groups of adolescents
      were identified according to the strategies they deployed. Four of them, i.e.
      optimistic, defensive pessimistic, self-handicapping and learned helplessness
      strategies, were similar to those described previously in the literature. The
      results showed that membership in the functional strategy groups, such as in
      mastery-oriented and defensive pessimist groups, was associated with well-being,
      school adjustment and achievement, and low levels of norm-breaking behaviour. By
      contrast, membership in the dysfunctional, for example self-handicapping and
      learned helplessness strategy groups, was associated with low levels of well
      being, and of school adjustment, and a higher level of norm-breaking behaviour.

PMID- 12009749
TI  - "I met this wife of mine and things got onto a better track" turning points in
      risk development.
AB  - In this study, qualitative and quantitative approaches were combined to study the
      mechanisms involved in turning-point experiences among individuals who had been
      exposed to several risk factors in childhood and adolescence. The study was part
      of the Jyvaskyla Longitudinal Study of Personality and Social Development, in
      which the lives of the participants (196 boys and 173 girls) have been followed
      from age 8 to age 36. The data concerning turning points was collected by semi
      structured interview when the participants were 36 years old. Participants were
      classified into six developmental trajectories according to risk factors at ages
      8-14 and problems of social functioning at age 36. The results showed that
      individuals with an unsuccessful childhood constructed their life courses less
      often in terms of education, work and social transitions compared to others.
      Those who were managing well in their lives at age 36, despite several risk
      factors in childhood (resilients) reported positive experiences and plenty of
      choice in relation to their turning points. Participants in the vulnerable
      subgroup, for their part, perceived turning points more negatively, and reported
      few opportunities for personal choice. Altogether, the results indicate that
      childhood experiences influence the content of turning points in adult life by
      shaping the direction of actual life paths. The quality of current life, however,
      has a greater bearing on the way turning points are evaluated.

PMID- 12009750
TI  - Occupational dreams, choices and aspirations: adolescents' entrepreneurial
      prospects and orientations.
AB  - The present study examined possible early antecedents of entrepreneurship of 14
      17-year-old 10th grade students (n=320). We hypothesized that Entrepreneurial
      Orientation (interest and self-efficacy), together with Willingness to Expend
      Effort, would be an important predictor of an adolescent's Entrepreneurial
      Prospects, i.e. prospects of becoming self-employed in the future. Furthermore,
      personality and the model of self-employed family were expected to predict the
      level of Entrepreneurial Orientation. The same relationships were investigated
      separately for students who were more or less willing to expend effort. Among
      students more willing to expend effort, levels of Entrepreneurial Orientation
      were higher for those who were conscientious, self-efficient, open to new
      experiences, and low in agreeableness. Among students less willing to expend
      effort, a high need for social recognition predicted higher levels of
      Entrepreneurial Orientation. In addition, parents' model for them was connected
      with lower levels of Entrepreneurial Orientation. A moderating effect of
      Willingness to Expend Effort was supported by the results for parents' model and
      need for social recognition.

PMID- 12009751
TI  - Personality types of adolescents: concurrent correlates, antecedents, and type X
      parenting interactions.
AB  - The concurrent correlates and developmental antecedents of personality types were
      investigated in a sample of 305 14-19-year-old Dutch adolescents. Concurrent
      characteristics and developmental antecedents included adjustment and parental
      control. We also examined whether parental control interacted with personality
      type in exaggerating differences among the types. The three main personality
      types (Resilients, Overcontrollers, and Undercontrollers) with behavioral and
      parenting correlates and antecedents were identified. We also found evidence for
      a moderator effect of restrictive control, particularly for Undercontrollers.
      Discussion highlights the importance of the family environment in understanding
      behavioral correlates of types.

PMID- 12009752
TI  - Parental and peer attachment and identity development in adolescence.
AB  - The main aim of this study was to test the situational hypothesis of parent-peer
      conflict and the parent-peer linkages hypothesis with regard to parental and peer
      attachment and identity. The situational hypothesis predicts that parental
      attachment will be associated with school identity and peer attachment with
      relational identity. The parent-peer linkages hypothesis suggests that parental
      attachment influences peer attachment and through peer attachment school and
      relational identity. Data from a survey of 148 middle adolescents from various
      ethnic groups were used. The findings offer strong support for the situational
      hypothesis, and only limited evidence in favor of the parent-peer linkages
      hypothesis. In addition, systematic links were found between parent and peer
      trust and commitment, and parent and peer communication and exploration.
      Adolescents from ethnic minority groups reported higher levels of school
      commitment and exploration compared with indigenous Dutch adolescents.

PMID- 12009753
TI  - Stability of attachment representations during adolescence: the influence of ego
      identity status.
AB  - The purpose of this study was to examine two core assumptions of attachment
      theory. First, internal working models of attachment should increase in stability
      during the course of development. Second, attachment is related to the adaptive
      solution of stage-salient issues, in adolescence, specifically to identity
      formation. Adolescence as a developmental period of change and reorganization
      might lead to changes in attachment representations by re-evaluating one's life
      experiences in the course of general identity development. In a longitudinal
      study, the stability of attachment representations (assessed by the Adult
      Attachment Interview) between ages 16 and 18 was examined. In addition, the
      concurrent and longitudinal associations of identity status at age 16 with
      attachment representations at ages 16 and 18 were tested. Results showed high
      stability of attachment representation during that age period. Secure attachment
      representation was positively associated with the identity status achievement,
      whereas a dismissing status was positively associated with identity diffusion.
      Longitudinally, identity diffusion at age 16 predicted attachment representation
      at age 18 even after controlling for earlier attachment representation.

PMID- 12009754
TI  - Personal agency and personality in adolescence: silent voices and findings.
AB  - We discuss the studies reported in this special issue on the basis of a
      descriptive framework. We conclude that implicit assumptions-silent voices, as we
      call them-concerning the transactional influence between person and environment,
      and concerning the primacy of personal agency exist side by side. We find in the
      studies both a variable-centred and a person-centred approach, and show that the
      person-centred approach can complement the variable-centred approach in a
      fruitful manner. On the other hand, both approaches seem to lead to similar
      results in the studies reported in this special issue. As a rule, the approaches
      lead to characterization of categories of adolescents, and moreover they can both
      be seen as exemplifying transactional thinking in the psychology of adolescence.
      Personal agency and personality are systematically correlated with developmental
      outcomes, but there are no strong indications that personal agency and
      personality are important predictors of later developmental outcomes. Such
      indications are found to a greater extent as regards the influence of parenting
      and the quality of the parent-adolescent relationship. Finally, there is evidence
      that peers have their own specific significance in the exploration of
      developmental options.

PMID- 12009755
TI  - Distinct nuclear and cytoplasmic localization of caspase cleavage products in two
      models of induced apoptotic death in dopamine neurons of the substantia nigra.
AB  - An emerging theme in programmed cell death (PCD) of neurons is that the
      mechanisms involved depend on the cellular context and the death-inducing
      stimulus. One particular class of neurons for which it is important to identify
      the mechanisms of PCD are the dopamine neurons of the substantia nigra, the
      neurons which degenerate in Parkinson's disease. PCD has been shown to occur in
      these neurons during normal development and to be induced in neurotoxin models of
      parkinsonism. Conventional histologic stains and TUNEL labeling have not revealed
      morphologic differences in the apoptosis observed in these neurons in any
      context. We now show that in two models of induced PCD in postmitotic dopamine
      neurons, one induced by early striatal target injury and another induced by the
      neurotoxin 6-hydroxydopamine (6OHDA), there are differences in the cellular
      localization and type of caspase cleavage products. Using two antibodies to
      caspase cleavage products (fractin and AB127), we show that in the target lesion
      model immunostaining is localized to the nucleus, whereas in the 6OHDA model
      intense cytoplasmic as well as nuclear staining is observed. Another antibody,
      AB246, to a caspase cleavage product of spectrin, immunostains apoptotic profiles
      only in the 6OHDA model. These findings suggest that the cellular compartment and
      therefore the role of the caspases may differ in apoptosis induced in pathologic
      settings, such as that due to neurotoxins, from that observed in models of
      natural or induced natural cell death. It will be important to recognize these
      differences in the consideration of caspase inhibitors in the treatment of
      degenerative neurologic disease.

PMID- 12009756
TI  - Localization of beta-secretase memapsin 2 in the brain of Alzheimer's patients
      and normal aged controls.
AB  - Chronic accumulation of beta-amyloid in the brain has been shown to result in
      complex molecular and cellular changes that accompany neurodegeneration in
      Alzheimer's disease (AD). In this study, we examined the expression of a newly
      identified beta-secretase, memapsin 2 (M2) or beta-site APP cleaving enzyme in
      deparaffinized sections from 10 AD patients and 10 aged matched controls and in
      frozen samples of parietal cortex from 11 AD and 8 controls. M2 is mainly
      expressed in neurons, with high levels in CA4 to CA2 regions and transentorhinal
      cortex and low or intermediate levels in CA1, subiculum, and granule cells of the
      dentate gyrus. The majority of AD brains showed an increase of M2 expression in
      the CA1, but a decrease in the transentorhinal cortex. A subset of controls and
      AD patients had high M2 expression in parietal neocortex. Double-staining
      revealed that senile plaques are not directly associated with the soma of M2
      expressing neurons. Neurofibrillary tangles were associated with lower M2
      expression in AD. These data indicate that beta-secretase M2 may not be
      straightforwardly involved in amyloid plaque formation in AD brain.

PMID- 12009757
TI  - Effect of lumbar 5 ventral root transection on pain behaviors: a novel rat model
      for neuropathic pain without axotomy of primary sensory neurons.
AB  - A peripheral nerve injury often causes neuropathic pain but the underlying
      mechanisms remain obscure. Several established animal models of peripheral
      neuropathic pain have greatly advanced our understanding of the diverse
      mechanisms of neuropathic pain. A common feature of these models is primary
      sensory neuron injury and the commingle of intact axons with degenerating axons
      in the sciatic nerve. Here we investigated whether neuropathic pain could be
      induced without sensory neuron injury following exposure of their peripheral
      axons to the milieu of Wallerian degeneration. We developed a unilateral lumbar 5
      ventral root transection (L5 VRT) model in adult rats, in which L5 ventral root
      fibers entering the sciatic nerve were sectioned in the spinal canal. This model
      differs from previous ones in that DRG neurons and their afferents are kept
      uninjured and intact afferents expose to products of degenerating efferent
      ventral root fibers in the sciatic nerve and the denervated muscles. We found
      that the L5 VRT produced rapid (24 h after transection), robust and prolonged (56
      days) bilateral mechanical allodynia, to a similar extent to that in rats with L5
      spinal nerve transection (L5 SNT), cold allodynia and short-term thermal
      hyperalgesia (14 days). Furthermore, L5 VRT led to significant inflammation as
      demonstrated by infiltration of ED-1-positive monocytes/macrophages in the DRG,
      sciatic nerve and muscle fibers. These findings demonstrated that L5 VRT produced
      behavioral signs of neuropathic pain with high mechanical sensitivity and thermal
      responsiveness, and suggested that neuropathic pain can be induced without damage
      to sensory neurons. We propose that neuropathic pain in this model may be
      mediated by primed intact sensory neurons, which run through the milieu of
      Wallerian degeneration and inflammation after nerve injury. The L5 VRT model
      manifests the complex regional pain syndrome in some human patients, and it may
      provide an additional dimension to dissect out the mechanisms underlying
      neuropathic pain.

PMID- 12009758
TI  - Behavioral and neurochemical effects of wild-type and mutated human alpha
      synuclein in transgenic mice.
AB  - Human alpha-synuclein (halpha-SYN) is implicated in the Parkinson's disease
      phenotype (PDP) based on a variety of studies in man, animal models, and in vitro
      studies. The normal function of halpha-SYN and the mechanism by which it
      contributes to the PDP remains unclear. We created transgenic mice expressing
      either wild-type (hwalpha-SYN) or a doubly mutated (hm2alpha-SYN) form of halpha
      SYN under control of the 9-kb rat tyrosine hydroxylase promoter. These mice
      expressed halpha-SYN in cell bodies, axons, and terminals of the nigrostriatal
      system. The expression of halpha-SYN in nigrostriatal terminals produced effects
      in both constructs resulting in increased density of the dopamine transporter and
      enhanced toxicity to the neurotoxin MPTP. Expression of hm2alpha-SYN reduced
      locomotor responses to repeated doses of amphetamine and blocked the development
      of sensitization. Adult hwalpha-SYN-5 transgenic mice had unremarkable
      dopaminergic axons and terminals, normal age-related measures on two motor
      coordination screens, and normal age-related measures of dopamine (DA) and its
      metabolites. Adult hm2alpha-SYN-39 transgenic mice had abnormal axons and
      terminals, age-related impairments in motor coordination, and age-related
      reductions in DA and its metabolites. Expression of hm2alpha-SYN adversely
      affects the integrity of dopaminergic terminals and leads to age-related declines
      in motor coordination and dopaminergic markers.

PMID- 12009759
TI  - Immortalized chromaffin cells disimmortalized with Cre/lox site-directed
      recombination for use in cell therapy for pain after partial nerve injury.
AB  - To prepare immortalized adrenal chromaffin cells for eventual clinical use, the
      immortalizing oncogene must be removed. We have utilized a Cre-mediated excision
      of a loxP-flanked Tag sequence to test whether immortalized chromaffin cells
      could be disimmortalized by this method. Cultures of embryonic rat adrenal cells
      were immortalized with the tsA-TN retroviral vector encoding the loxP-flanked
      temperature-sensitive allele of SV40 large T antigen (tsA-TN) and a
      positive/negative neo/HSV-TK sequence for selection with either G418 or
      gancyclovir, respectively. These cells were then infected with the 1710-CrePR1
      bicistronic retroviral vector coding for a form of Cre modulatable by the
      synthetic steroid RU486. These immortalized loxTsTag/CrePR1/RAD cells expressed
      immunoreactivities (ir) for all the catecholamine enzymes: tyrosine hydroxylase
      (TH), dopamine beta-hydroxylase (DbetaH), and phenylethanolamine-N
      methyltransferase (PNMT). After initial incubation at 37 degrees C with RU486 for
      3 days, followed by the addition of gancyclovir for 7 days, Tag-ir was not
      detectable in most of the surviving chromaffin cells, compared to 100% expression
      in immortalized loxTsTag/CreR1/RAD cells not treated with RU486 and gancyclovir.
      The expression of TH, DbetaH, and PNMT was increased after disimmortalization and
      the ability of disimmortalized cells to synthesize norepinephrine was also
      significantly increased compared to immortalized cells. When both types of
      chromaffin cells were transplanted in a model of neuropathic pain and partial
      nerve injury, both cell grafts were equally able to reverse the behavioral
      hypersensitivity induced by the injury. The use of Cre/lox site-directed
      disimmortalization of chromaffin cells that are able to deliver neuroactive
      molecules offers a novel approach to cell therapy.

PMID- 12009760
TI  - Injury-induced class 3 semaphorin expression in the rat spinal cord.
AB  - In this study we evaluate the expression of all members of the class 3
      semaphorins and their receptor components following complete transection and
      contusion lesions of the adult rat spinal cord. Following both types of lesions
      the expression of all class 3 semaphorins is induced in fibroblast in the neural
      scar. The distribution of semaphorin-positive fibroblasts differs markedly in
      scars formed after transection or contusion lesion. In contusion lesions
      semaphorin expression is restricted to fibroblasts of the meningeal sheet
      surrounding the lesion, while after transection semaphorin-positive fibroblast
      penetrate deep into the center of the lesion. Two major descending spinal cord
      motor pathways, the cortico- and rubrospinal tract, continue to express receptor
      components for class 3 semaphorins following injury, rendering them potentially
      sensitive to scar-derived semaphorins. In line with this we observed that most
      descending spinal cord fibers were not able to penetrate the semaphorin positive
      portion of the neural scar formed at the lesion site. These results suggest that
      the full range of secreted semaphorins contributes to the inhibitory nature of
      the neural scar and thereby may inhibit successful regeneration in the injured
      spinal cord. Future studies will focus on the neutralization of class 3
      semaphorins, in order to reveal whether this creates a more permissive
      environment for regeneration of injured spinal cord axons.

PMID- 12009761
TI  - Intrinsic optical imaging reveals regionally different manifestation of spreading
      depression in hippocampal and entorhinal structures in vitro.
AB  - The spatiotemporal features of spreading depression (SD) were analyzed in vitro
      by using combined hippocampal-entorhinal cortex slices. SDs were induced by
      microinjection of 1 M KCl in the stratum radiatum of the CA1 region of the
      hippocampus. Measurements of extracellular field potentials, extracellular space
      (ECS) volume changes and intrinsic optical signal changes were combined to study
      SD features in different regions of the slice. Each SD was associated with a
      pronounced shrinkage of the extracellular space (ECS) volume and a decrease in
      light transmittance. The beginning of the optical signal change occurred
      simultaneously with the electrographic onset as measured with extracellular
      microelectrodes but outlasted the dc shift for tens of seconds. The amplitude of
      the intrinsic optical signal change displayed marked regional variations with
      greatest changes of 12% in cortical regions. The signal amplitudes were
      considerably lower in hippocampal regions. The analysis of spread patterns
      revealed two types of waves: fully propagated waves spreading from CA1 all the
      way to the temporal neocortex and abortive waves that ceased earlier. The spread
      velocities displayed pronounced regional differences with highest velocities of
      5.4 +/- 0.3 mm/min in the area CA3 of the hippocampal formation and lowest
      velocities of 2.7 +/- 0.1 mm/min in cortical regions.

PMID- 12009762
TI  - Progressive loss of striatal neurons causes motor dysfunction in MND2 mutant mice
      and is not prevented by Bcl-2.
AB  - The mouse mutant "motoneuron disease 2" (MND2, mnd2 on Chr 6) was originally
      characterized as a spinal muscular atrophy (SMA) because degenerating motoneurons
      were observed in late stages of the disease. MND2 mutants exhibit a progressive
      phenotype with neurological symptoms that begin at postnatal day (dP) 20 and
      include involuntary movements, abnormal postures, akinesis, and death between dP
      30 and 40. Unexpectedly, there was no induction of acetylcholine receptor alpha
      subunit mRNA in skeletal muscle of MND2 mice, an indicator of muscle denervation
      due to motoneuron loss. Rather, we found a massive loss of striatal neurons
      beginning at dP 25. Histochemical and ultrastructural analysis revealed nuclear
      pyknosis, chromatin condensation, and organelle disintegration, combined features
      of apoptosis and necrosis, characteristic for excitotoxic cell death. Striatal
      neurodegeneration was accompanied by a pronounced astrogliosis and activation of
      microglia with macrophage morphology. Motor abnormalities and neuronal loss in
      MND2 mice were not prevented by neuronal overexpression of a Bcl-2 transgene.
      Transcripts of several cytokines, including Interleukin-1beta and tumor necrosis
      factor alpha, were upregulated in the CNS, as well as in lung and spleen,
      indicating that the mnd2 mutation causes additional pathological effects outside
      the CNS. Since a 50% reduction in the number of striatal neurons is sufficient to
      account for the neurological phenotype of MND2 mice, MND2 may be classified as
      striatal atrophy rather than a primary motor neuron disease. Thus, MND2 mutant
      mice may provide useful insights into molecular events underlying striatal cell
      death.

PMID- 12009763
TI  - The potential for circuit reconstruction by expanded neural precursor cells
      explored through porcine xenografts in a rat model of Parkinson's disease.
AB  - Neural precursors with the properties of neural stem cells can be isolated from
      the developing brain, can be expanded in culture, and have been suggested as a
      potential source of cells for neuronal replacement therapies in degenerative
      disorders such as Parkinson's disease (PD). Under such conditions an improved
      spectrum of functional benefit may be obtained through homotypic reconstruction
      of degenerated neural circuitry, and to this end we have investigated the
      potential of expanded neural precursor cells (ENPs) to form long axonal
      projections following transplantation in the 6-hydroxydopamine-lesioned rat model
      of PD. ENPs have been isolated from the embryonic pig, since implantation in a
      xenograft environment is thought to favor axonal growth. These porcine ENPs
      possessed similar properties in vitro to those described in other species: they
      proliferated in response to epidermal and fibroblast growth factor-2, expressed
      the neuroepithelial marker nestin, and differentiated into neurons, astrocytes,
      and occasional oligodendrocytes on mitogen withdrawal. The use of pig-specific
      markers following xenotransplantion into cyclosporin A-immunosuppressed rats
      revealed that many cells differentiated into neurons and displayed extensive
      axogenesis, such that when placed in the region of the substantia nigra fibers
      projected throughout the striatal neuropil. These neurons were not restricted in
      the targets to which they could project since following intrastriatal grafting
      fibers were seen in the normal striatal targets of the pallidum and substantia
      nigra. Staining for a pig-specific synaptic marker suggested that synapses were
      formed in these distant sites. A small number of these cells differentiated
      spontaneously to express a catecholaminergic phenotype, but were insufficient to
      mediate behavioral recovery. Our results suggest that when the efficiency of
      neurochemical phenotype induction is increased, ENP-derived neurons have the
      potential to be a uniquely flexible source of cells for therapeutic cell
      replacement where anatomical reconstruction is advantageous.

PMID- 12009764
TI  - Efficacy of myoblast transplantation in nonhuman primates following simple
      intramuscular cell injections: toward defining strategies applicable to humans.
AB  - Nonhuman primates were used to define myoblast transplantation strategies
      applicable to humans. Nevertheless, previous experiments were based on the use of
      myotoxins concomitant with the myoblast injections. Since myotoxins must be
      avoided for clinical applications, we analyzed the efficacy of simple myoblast
      injections (i.e., myoblasts resuspended only in saline) into monkey muscles. We
      also evaluated different FK506 dosages (in combination or not with mycophenolate
      mofetil) for immunosuppression. Allogeneic myoblasts transduced with the beta
      galactosidase (beta-Gal) gene were implanted in the muscles of 19 monkeys by
      injections placed 1 to 2 mm from each other. A biopsy was performed at the
      implanted sites 1 month later, and histologically studied for demonstration of
      beta-Gal+ myofibers, lymphocyte infiltration, and CD8+ cells. The presence of
      antibodies against the donor myoblasts and the blood levels of FK506 were
      analyzed. Our results show that: (1) If myoblast injections are sufficiently
      close to each other, high percentages of hybrid myofibers can be obtained
      following myoblast transplantation in primates (25 to 67% with an interinjection
      distance of 1 mm). (2) Efficient immunosuppression can be reached by increasing
      FK506 dosages, but also by combining this drug with mycophenolate mofetil, a
      combination that reduces toxic effects. The present results represent a step
      towards a better designing of myoblast transplantation strategies in humans.

PMID- 12009765
TI  - FK506 increases peripheral nerve regeneration after chronic axotomy but not after
      chronic schwann cell denervation.
AB  - Poor functional recovery after peripheral nerve injury is attributable, at least
      in part, to chronic motoneuron axotomy and chronic Schwann cell (SC) denervation.
      While FK506 has been shown to accelerate the rate of nerve regeneration following
      a sciatic nerve crush or immediate nerve repair, for clinical application, it is
      important to determine whether the drug is effective after chronic nerve
      injuries. Two models were employed in the same adult rats using cross-sutures:
      chronic axotomy and chronic denervation of SCs. For chronic axotomy, a
      chronically (2 months) injured proximal tibial (TIB) was sutured to a freshly cut
      common peroneal (CP) nerve. For chronic denervation, a chronically (2 months)
      injured distal CP nerve was sutured to a freshly cut TIB nerve. Rats were given
      subcutaneous injections of FK506 or saline (5 mg/kg/day) for 3 weeks. In the
      chronic axotomy model, FK506 doubled the number of regenerated motoneurons
      identified by retrograde labeling (from 205 to 414 TIB motoneurons) and increased
      the numbers of myelinated axons (from 57 to 93 per 1000 microm2) and their myelin
      sheath thicknesses (from 0.42 to 0.78 microm) in the distal nerve stump. In
      contrast, after chronic denervation, FK506 did not improve the reduced capacity
      of SCs to support axonal regeneration. Taken together, the results suggest that
      FK506 acts directly on the neuron (as opposed to the denervated distal nerve
      stump) to accelerate and promote axonal regeneration of neurons whose
      regenerative capacity is significantly reduced by chronic axotomy.

PMID- 12009766
TI  - Sequential interactions of fibroblast growth factor-2, brain-derived neurotrophic
      factor, neurotrophin-3, and their receptors define critical periods in the
      development of cochlear ganglion cells.
AB  - We studied the interactions of neurotrophin-3 (NT3) with brain-derived
      neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF-2), and their effects
      on tyrosine kinase C (TrkC) expression during cochlear ganglion development.
      Otocysts were explanted from white leghorn chicken embryos at stages when the
      neuronal precursors normally start to migrate. Cultures were fed with various
      combinations of NT3, BDNF, and FGF-2. NT3 appeared to have a greater effect on
      neurite outgrowth than on migration and was enhanced by BDNF. The results from in
      situ hybridization and immunostaining for TrkC receptor revealed up-regulation of
      the mRNA and protein by combining NT-3 and BDNF. NT-3 combined with FGF-2
      produced down-regulation of receptor. Neutralizing antibody to NT3 had an
      inhibitory effect on neuronal development, suggesting that endogenous NT3 is
      normally active during the period examined. The findings suggest an interactive
      role of NT3 in early neuronal development. The trophic synergism of NT3 and BDNF
      may result from up-regulation of TrkC. This hypothesis is consistent with
      immunostaining in the embryonic basilar papilla, which localized TrkC to the
      initial axonal invasion sites. While the growth factors each produce particular
      trophic effects, the interactions of these factors define a critical sequence of
      developmental events based on modulation of receptor expression.

PMID- 12009767
TI  - Cyclooxygenase-2 and caspase 3 expression in trimethyltin-induced apoptosis in
      the mouse hippocampus.
AB  - The neurotoxicant trimethyltin (TMT) induces massive neuronal loss in vivo in the
      hippocampus of rodents, accompanied by behavioral alterations. The present study
      investigates the pattern of cell death after in vivo administration of TMT to
      adult mice. In the granular cell layer of the Dentate Gyrus, TUNEL staining
      detected DNA fragmentation, and apoptotic bodies were also evident. In addition,
      a ladder pattern of internucleosomal DNA fragmentation was shown in agarose gel
      electrophoresis. We show that activated caspase-3, which is known to play a
      pivotal role in apoptotic processes, is clearly expressed by degenerating
      neurons. Inducible cyclooxygenase is also expressed at cytoplasmic level by
      degenerating granular neurons, suggesting that this enzyme may participate in TMT
      induced neurodegeneration.

PMID- 12009768
TI  - Phenformin suppresses calcium responses to glutamate and protects hippocampal
      neurons against excitotoxicity.
AB  - Phenformin is a biguanide compound that can modulate glucose metabolism and
      promote weight loss and is therefore used to treat patients with type-2 diabetes.
      While phenformin may indirectly affect neurons by changing peripheral energy
      metabolism, the possibility that it directly affects neurons has not been
      examined. We now report that phenformin suppresses responses of hippocampal
      neurons to glutamate and decreases their vulnerability to excitotoxicity.
      Pretreatment of embryonic rat hippocampal cell cultures with phenformin protected
      neurons against glutamate-induced death, which was correlated with reduced
      calcium responses to glutamate. Immunoblot analyses showed that levels of the N
      methyl-d-aspartate (NMDA) subunits NR1 and NR2A were significantly decreased in
      neurons exposed to phenformin, whereas levels of the AMPA receptor subunit GluR1
      were unchanged. Whole-cell patch clamp analyses revealed that NMDA-induced
      currents were decreased, and AMPA-induced currents were unchanged in neurons
      pretreated with phenformin. Our data demonstrate that phenformin can protect
      neurons against excitotoxicity by differentially modulating levels of NMDA
      receptor subunits in a manner that decreases glutamate-induced calcium influx.
      These findings show that phenformin can modulate neuronal responses to glutamate,
      and suggest possible use of phenformin and related compounds in the prevention
      and/or treatment of neurodegenerative conditions.

PMID- 12009769
TI  - Regional differences in the Purkinje cells settled pattern: a comparative
      autoradiographic study in control and homozygous weaver mice.
AB  - To determine whether Purkinje cells located in the vermis and the lateral
      hemispheres of weaver mice homozygotes are distributed according to precise
      neurogenetic gradients, [3H]thymidine autoradiography was applied on sections of
      homozygous weaver mice and normal controls on postnatal day 90. The experimental
      animals were the offspring of pregnant dams injected with [3H]thymidine on
      embryonic days 11-12, 12-13, 13-14, and 14-15. The results indicate that, at the
      level of the vermis, neurogenetic gradients were similar for wild-type and
      homozygous weaver in each lobe studied of the cerebellar cortex. The same was
      found for the lobulus simplex and for the ansiform and paramedian lobules when
      the lateral hemisphere was considered. In the vermis of both experimental groups,
      the anterior and inferior lobes have more late-generated Purkinje cells than the
      central and posterior lobes, while in the lateral hemisphere, the lobulus simplex
      and the ansiform lobule present more early generated Purkinje cells than the
      paramedian lobule. In weaver homozygotes, the most important deficit of Purkinje
      cells, in the region of the vermis, was observed in the central lobe; depletion
      was less observable in the anterior lobe and least observable in the posterior
      and inferior lobes. In the lateral hemispheres, the most important loss of
      Purkinje cells was observed in the paramedian lobule, followed by the lobulus
      simplex. The ansiform lobule presented values that showed no statistical
      difference between control and homozygous weaver. When Purkinje cells were
      registered in the entire sections, no significant differences were observed
      between the two experimental groups. This was due to a considerable volume of the
      weaver homozygote cerebellar tissue, which has no counterpart in the control
      mice, compensating for the neuronal loss observed in the other studied areas of
      the lateral hemisphere.

PMID- 12009770
TI  - The effects of ACTH and adrenocorticosteroids on seizure susceptibility in 15-day
      old male rats.
AB  - Infantile spasms are generalized convulsive seizures seen in the first year of
      life. They respond poorly to conventional anticonvulsants, but are often
      controlled by adrenocorticotropic hormone (ACTH) therapy. Other childhood
      seizures are also responsive to ACTH. The present study tested the effects of
      ACTH and related adrenocorticosteroids in prepubertal, 15-day-old rats. Compounds
      were tested against minimal (scMET) and maximal (MMT) pentylenetetrazol seizures,
      maximal electroconvulsive shock (MES) seizures, and hippocampal kindled seizures.
      ACTH had no significant anticonvulsant effects against any type of seizure.
      Several of the adrenocorticoid hormones, however, had strong anticonvulsant
      effects. Deoxycorticosterone (DOC) and progesterone (P4) both significantly
      suppressed scMET, MMT, and MES seizures 15 min after s.c. injection. DOC and P4
      also shortened hippocampal discharge duration in the kindling model, and DOC, but
      not P4, suppressed the kindled convulsion. Aldosterone and corticosterone were
      effective against scMET seizures, and aldosterone was effective against MMT
      seizures. Dexamethasone and dihydroepiandrosterone had no anticonvulsant
      activity. These findings indicate that the adrenal steroid precursors, DOC and
      P4, have a broad spectrum of anticonvulsant activity in animal seizure models.
      They may play a role in mediating the anticonvulsant effects of ACTH in human
      infants.

PMID- 12009771
TI  - Effect of bilateral hypogastric nerve transection on voiding dysfunction in rats
      with spinal cord injury.
AB  - We determined if bilateral section of the hypogastric nerves (HGN), which provide
      the major sympathetic input to the urinary bladder neck/proximal urethra, could
      improve voiding by reducing urethral resistance in conscious, female spinal-cord
      injured (SCI) rats 2-3 weeks after T(7-9) transection of the spinal cord.
      Cystometry was performed in animals with HGN intact and with HGN sectioned
      bilaterally 1-2 h before the experiment. Residual volume (RV), volume threshold
      for inducing micturition (VT), maximal voiding pressure, and bladder compliance
      were significantly lower (71, 35, 33, and 31%, respectively) in SCI rats with
      sectioned HGN than in rats with intact HGN, whereas voided volume (VV), pressure
      threshold for micturition, and bladder contraction duration (BCD) in the two
      groups were similar. Voiding efficiency (VE) in the HGN-sectioned group was 36%
      greater than that in the HGN-intact group. Antagonists for AMPA and NMDA
      glutamatergic receptors (LY215490 and MK-801, respectively) were administered to
      rats with sectioned HGN, to determine if activity in the HGN contributes to the
      previously reported inhibitory effects of these drugs, on voiding function after
      SCI. MK-801 (3 mg/kg iv) significantly reduced VV (75%) and VE (85%) and
      increased RV (8-fold), VT (87%), and bladder compliance (60%), whereas LY215490
      (10 mg/kg iv) significantly increased VT and BCD by 15 and 19%, respectively. It
      is concluded that bilateral section of HGN reduces voiding dysfunction in the SCI
      rat but does not alter the effects of AMPA and/or NMDA glutamatergic receptor
      antagonists on the micturition reflex in the SCI rat. Thus the effects of these
      drugs are not dependent on changes in activity of sympathetic axons in the HGN.

PMID- 12009772
TI  - Rapid loss and partial recovery of neurofilament immunostaining following focal
      brain injury in mice.
AB  - Neurofilaments (NF), the intermediate filaments of the neuronal cytoskeleton,
      provide mechanical stability to the cell. High-molecular-weight NF (NFH)
      comprises a heavily phosphorylated carboxyl terminal ("sidearm") domain which
      helps determine interfilament spacing distances. Experimental evidence suggests
      that dephosphorylation greatly increases the rate and extent of proteolysis of
      NFH. Because NF proteolysis has been implicated as one pathogenic mechanism
      underlying cell death following traumatic brain injury (TBI), we analyzed the
      patterns of acute NFH damage in relation to phosphorylation state following
      focal, concussive, controlled cortical impact (CCI) brain injury in mice. Brains
      from C57BL/6 male mice (n = 4 injured and n = 1 sham per time point) were
      evaluated 5 min, 15 min, 90 min, 4 h, and 24 h following CCI injury (1 mm depth,
      5 m/s). Immunohistochemistry was performed using antibodies that recognize
      epitopes on either dephosphorylated (d-NFH) or phosphorylated (p-NFH) sidearms or
      on the core (c-NFH) domain. As early as 5-15 min postinjury, immunoreactivity for
      d-, p-, and c-NFH decreased in the ipsilateral cortex, and hippocampal CA3, CA1,
      and dentate areas. This marked decrease of NFH labeling occurred in the absence
      of notable cell loss. Furthermore, partial recovery of NFH labeling was observed
      as early as 90 min postinjury in the cortex and by 24 h postinjury in hippocampal
      CA3 and dentate. The results of this study suggest that both phosphorylated and
      dephosphorylated NFH are vulnerable almost immediately following focal brain
      injury in mice, but that injured neurons may have an adaptive capability to
      partially restore this important cytoskeletal protein.

PMID- 12009773
TI  - Tuning of membrane properties regulates subliminal synapses in dorsal horn
      neurons of intact rats.
AB  - Functional plasticity in receptive field properties underlies the mechanism
      whereby spinal dorsal horn neurons encode changes in pain sensitivity following
      peripheral injury. Activation of "silent" or subliminal excitatory synapses was
      hypothesized to account for this injury-induced neural plasticity. To better
      characterize the mechanisms governing subliminal inputs, we adapted whole-cell
      patch clamp to the study of dorsal horn neurons in intact, anesthetized rats. In
      this report we show that the membrane properties of spinal cells correlate to
      functional class defined by action potential responses to cutaneous stimuli. In
      addition, we report the discovery of a novel "silent" population of neurons with
      solely subliminal excitatory inputs at rest that can be activated by membrane
      depolarization. Finally, an induced change in baseline membrane potential to a
      level nearer that of a different functional class results in a corresponding
      change in the responses to cutaneous stimuli of a given cell to that of the new
      functional class. In summary our findings suggest that biophysical membrane
      properties are key factors determining the functional profile of spinal neurons.
      The rapid change of such properties may regulate the function of silent synapses
      in spinal neurons and underlie rapid development of neural plasticity.

PMID- 12009774
TI  - Oxidative stress involves in astrocytic alterations induced by manganese.
AB  - It is hypothesized that manganese neurotoxicity could be secondary to a
      diminution of cellular protective and scavenger mechanisms. Since manganese is
      known to be sequestered in glial cells, we investigated possible neurotoxic
      mechanisms involving astrocytes in vitro. Astrocytes differentiated into process
      bearing stellate cells in response to manganese treatment. Manganese
      concentration dependently decreased cellular DNA synthesis, glial fibrillary
      acidic protein expression, energy production, antioxidant capacity, and glutamate
      transporter activity. In contrast, manganese increased glutamine synthetase
      protein expression and cytokine-stimulated interleukin 6 mRNA expression. Under
      the concentration of 0.1 mM, manganese chloride caused no significant astrocyte
      death even up to 48 h after treatment. That is, these astrocytic alterations
      proceeded before the onset of cell demise. As a possible mediator of manganese
      derived alterations, we determined intracellular redox state in astrocytes.
      Manganese time-dependently changed intracellular redox potential into oxidized
      state. The influx of manganese and its resultant oxidative stress was essential
      to most of the alterations, except for the action on stellation. Astrocytes are
      central component of the brain's antioxidant defense. Therefore, the observations
      suggest that dysfunction of astrocytes possibly involved in neurotoxic action of
      manganese.

PMID- 12009775
TI  - Transcription factor modulation and expression in the rat auditory brainstem
      following electrical intracochlear stimulation.
AB  - Neuronal activity in sensory organs elicited by adequate or electrical
      stimulation not only invokes fast electrical responses but may also trigger
      complex molecular changes inside central neurons. Following electrical
      intracochlear stimulation with a cochlear implant under urethane anesthesia, we
      observed changes in the phosphorylation state of the cAMP response element
      binding protein (CREB) and the expression of the immediate-early genes c-fos and
      egr-1, molecules known to act as transcription factors, in a tonotopically
      precise pattern in central auditory neurons. These neurons resided in the
      posteroventral and anteroventral cochlear nucleus, the dorsal cochlear nucleus,
      the lateral superior olive, the medial nucleus of the trapezoid body, the dorsal
      and ventral nucleus of the lateral lemniscus, and the central nucleus of the
      inferior colliculus. Moreover, effects of electrical stimulation were identified
      in the medial vestibular nucleus and the lateral parabrachial nucleus.
      Regionally, CREB was dephosphorylated wherever immediate-early gene expression
      went up. These massive stimulation-dependent modulations of transcription factors
      in the ascending auditory system are indicative of ongoing changes that modify
      the chemistry and structure of the affected cells and, consequently, their
      response characteristics to subsequent stimulation of the inner ear.

PMID- 12009776
TI  - Protein kinase C regulates [3H]D-aspartate release in auditory brain stem nuclei.
AB  - We previously found that unilateral cochlear ablation altered transmitter release
      from glutamatergic synaptic endings in several brain stem auditory nuclei. To
      determine if this release activity could be regulated by protein kinase C (PKC),
      which has been associated with regulation of transmitter release, the
      electrically evoked release of [3H]d-aspartate ([3H]d-Asp) was quantified in
      vitro as an index of exocytosis from glutamatergic presynaptic endings in the
      major subdivisions of the cochlear nucleus (CN) and in the main nuclei of the
      superior olivary complex (SOC). Treating dissected tissues with a PKC activator,
      such as phorbol 12,13-diacetate (PDA) or phorbol 12,13-dibutyrate (PDBu) (3
      microM), elevated the evoked release of [3H]d-Asp by 1.5- to 3.3-fold. The PKC
      inhibitor Ro31-8220 (50 nM) did not alter the evoked release but blocked the
      stimulatory effects of PDA and PDBu. These findings suggested that PKC could
      positively regulate transmitter release from glutamatergic presynaptic endings in
      brain stem auditory pathways. Seven days after unilateral cochlear ablation, when
      cochlear nerve endings had degenerated in the ipsilateral CN, PDBu elevated the
      evoked release bilaterally in each CN subdivision and SOC nucleus, implying that
      PKC could regulate glutamatergic release in the noncochlear pathways remaining in
      the ipsilateral CN and in the other pathways after unilateral hearing loss. After
      145 postlesion days, Ro31-8220 blocked endogenous elevations in the evoked
      release in the ipsilateral SOC but did not alter the elevated or upregulated
      release in the other tissues. This suggested that the elevations of glutamatergic
      release activity in the ipsilateral SOC that appeared after unilateral cochlear
      ablation depended on endogenous activation of PKC.

PMID- 12009777
TI  - Nicotine alters striatal glutamate function and decreases the apomorphine-induced
      contralateral rotations in 6-OHDA-lesioned rats.
AB  - The overall goal of this study was to determine the effects of subchronic
      nicotine (0.4 mg/kg) treatment for 7 or 14 days on striatal glutamate function in
      both naive and in 6-hydroxydopamine (6-OHDA)-treated rats in which the
      nigrostriatal dopamine pathway was lesioned. In lesioned animals, the effect of
      nicotine on apomorphine-induced contralateral rotations was also assessed. In
      naive rats, once daily nicotine administration for 7 or 14 days resulted in a
      decrease and then an increase, respectively, in the basal extracellular level of
      striatal glutamate compared to the saline-treated group. Ultrastructurally, 14
      day treatment with nicotine resulted in an increase in the density of striatal
      glutamate immunolabeling within nerve terminals making an asymmetrical synaptic
      contact compared to the saline-treated group. In 6-OHDA-lesioned animals,
      coadministration of nicotine with apomorphine or nicotine alone for 7 days
      resulted in an increase in the density of nerve terminal glutamate
      immunolabeling, compared to the apomorphine- or saline-treated groups. However,
      coadministration of nicotine with apomorphine for 14 days resulted in a decrease
      in the density of nerve terminal glutamate immunolabeling compared to the
      nicotine-treated group. Following subchronic treatment of 6-OHDA-lesioned rats
      with apomorphine for 7 or 14 days, there was an increase in the number of
      apomorphine-induced contralateral rotations compared to the saline treated group.
      There was a decrease in the number of apomorphine-induced contralateral rotations
      in the group coadministered nicotine with apomorphine for 7 or 14 days compared
      to the apomorphine treated group. The data suggests that in this 6-OHDA lesion
      model of Parkinson's disease, treatment with nicotine may be useful in
      counteracting the increased behavioral effect (i.e., contralateral rotations)
      observed after treatment with a dopamine agonist, such as apomorphine.

PMID- 12009778
TI  - Amphetamine-induced Fos expression is evident in gamma-aminobutyric acid neurons
      in the globus pallidus and entopeduncular nucleus in rats treated with
      intrastriatal c-fos antisense oligodeoxynucleotides.
AB  - Double immunostaining for Fos and gamma-aminobutyric acid (GABA) was used in a
      previously established animal model of striatal dysfunction to examine whether
      GABA-immunoreactive neurons in the globus pallidus (GP) and entopeduncular
      nucleus (EP) are activated to express Fos immunoreactivity by intraperitoneal
      injection of amphetamine. Striatal efferent activity was suppressed by
      intrastriatal infusions of antisense oligodeoxynucleotide targeted to the
      messenger RNA of the immediate early gene, c-fos. This suppression produced
      robust rotational behavior and expression of Fos in the ipsilateral GP and EP
      following amphetamine challenge. The expression of Fos in the ipsilateral GP and
      EP following amphetamine challenge is not observed in naive or control antisense
      treated animals. Quantitative analysis revealed that a majority of the
      amphetamine-activated (Fos-immunoreactive) neurons in the GP and EP express GABA.
      The present results suggest that inhibitory GABAergic projection neurons within
      these two nuclei are regulated by inhibitory striatal output and suggests that
      decreased inhibitory striatal output may contribute to the motor dysfunction
      observed in patients with Huntington's disease.

PMID- 12009779
TI  - Neurotrophins reduce degeneration of injured ascending sensory and corticospinal
      motor axons in adult rat spinal cord.
AB  - Spinal cord regeneration in adult mammals is limited by neurite outgrowth
      inhibitors and insufficient availability of outgrowth-promoting agents. Formation
      of degenerative swellings at the proximal ends of severed axons (terminal clubs),
      which starts early after injury, also may hinder recovery and their rupture may
      contribute to secondary spinal cord damage. We investigated whether neurotrophins
      would reduce these degenerative processes. Adult rats received a transection of
      the dorsal column sensory and corticospinal motor tracts at T9 and anterograde
      tracing of the axons from the sciatic nerve and motor cortex, respectively. The
      highest number of terminal clubs was found at 1 day and approximately half
      remained present until at least 28 days. A single injection immediately after
      injury of a mixture of nerve growth factor, brain-derived neurotrophic factor and
      neurotrophin-3 into the lesion site, reduced the number of terminal clubs in the
      sensory system by approximately half at 1 and 7 days (but not 14) after the
      lesion. Individual or combinations of two neurotrophins were as effective,
      suggesting that the neurotrophins protected similar axonal populations. The
      injected neurotrophins did not affect degeneration of corticospinal motor axons.
      A 7-day continuous intrathecal infusion of neurotrophin-3 was more effective and
      also reduced terminal club formation of corticospinal axons by approximately 60%.
      Spinal tissue loss was not affected by the neurotrophin treatments, suggesting
      that terminal clubs are not major contributors to the pathogenesis of secondary
      spinal degeneration during the first two weeks. Thus, neurotrophins can reduce
      axonal degeneration in the spinal cord after traumatic axonal injury.

PMID- 12009780
TI  - Maintenance of susceptibility to neurodegeneration following intrastriatal
      injections of quinolinic acid in a new transgenic mouse model of Huntington's
      disease.
AB  - A transgenic mouse model of Huntington's disease (R6/1 and R6/2 lines) expressing
      exon 1 of the HD gene with 115-150 CAG repeats resisted striatal damage following
      injection of quinolinic acid and other neurotoxins. We examined whether
      excitotoxin resistance characterizes mice with mutant huntingtin transgenes. In a
      new transgenic mouse with 3 kb of mutant human huntingtin cDNA with 18, 46, or
      100 CAG repeats, we found no change in susceptibility to intrastriatal injections
      of the excitotoxin quinolinic acid, compared to wild-type littermates. The new
      transgenic mice were injected with the same dose of quinolinic acid (30 nmol) as
      had been the R6 mice. Our findings highlight the importance of studying
      pathogenetic mechanisms in different transgenic models of a disease.

PMID- 12009781
TI  - Effect of hyaluronan on xenotransplanted breast cancer.
AB  - Hyaluronan is a major glycosaminoglycan component of the extracellular matrix and
      CD44 is its principal ligand. In previous in vitro studies we have shown that
      CD44 and hyaluronan are involved in the invasive properties of the human breast
      cancer cell line Hs578T. The aim of this study was to test whether experimental
      therapy with hyaluronan interferes with tumor invasion and has an inhibitory
      effect on tumor growth in vivo. The Hs578T cell line was xenotransplanted
      orthotopically into the mammary fat pad of nu/nu mice. After tumor growth reached
      a maximum size of 5 x 5 mm, 50 microg of hyaluronan was injected intratumorally.
      The tumors of control nu/nu mice were injected with PBS. Four of 12 tumors from
      the hyaluronan-treated group regressed completely. This effect could be due to a
      saturation of the hyaluronan-binding sites on tumor cells or to an acceleration
      of tumor rejection by a non-T-cell-dependent mechanism. This study gives a
      rationale for future work on the antineoplastic effects of hyaluronan.

PMID- 12009782
TI  - Tenascin-C expression and splice variant in habu snake venom-induced
      glomerulonephritis.
AB  - Extracellular matrix glycoprotein tenascin-C (TNC) expression is up-regulated in
      tissue remodeling processes such as tumorigenesis and wound healing. Mouse
      tenascin-C contains six alternatively spliced domains (A1, A2, A4, B, C, and D)
      between the fifth and the sixth type III fibronectin domains, which generate
      large numbers of TNC isoforms. To study TNC isoform variability of wound healing
      in mice, we induced glomerulonephritis by using Habu snake venom (HSV) and
      examined alternatively spliced regions by the reverse transcription polymerase
      chain reaction (RT-PCR) technique. RT-PCR products were separated into seven
      bands in both healthy and diseased kidneys. Among the seven bands, those
      containing one or five alternatively spliced domains were mainly up-regulated
      from 2 days to 1 week after HSV injection. Southern blotting revealed that only
      domain-D detected all six bands in both healthy and diseased kidneys.
      Furthermore, only the domain-C transcriptional level did not show an obvious
      change in progress following HSV injection. These results suggested that (a) the
      isoforms containing one or five alternatively spliced domains play important
      roles in the healing process of glomerulonephritis, (b) domain-D is particularly
      significant in kidney, and (c) domain-C may not play an important role in the
      healing process of HSV-induced glomerulonephritis.

PMID- 12009783
TI  - Cellular proteins bind to sequence motifs in the R1 element between the HCMV
      immune evasion genes.
AB  - The viral US3 and US6 gene products of human cytomegalovirus (CMV) are
      sequentially expressed at immediate-early and early times after infection,
      respectively. They downregulate the surface expression of HLA class I molecules.
      There are two repeat-containing regulatory regions between the US3 promoter and
      the US6 transcription unit designated R1 and R2. R2 contains repetitions of the
      NF-kappa B responsive element and enhances the immediate-early expression of the
      US3 gene. R1 contains 19 repetitions of a 5'-TRTCG-3' pentanucleotide arranged as
      everted repeats, inverted repeats, and variably spaced single pentanucleotides.
      In the context of the viral genome, R1 also enhances immediate-early US3 gene
      expression by an unknown mechanism (G. C. Bullock, et al., 2001, Virology 288,
      164-174). We report a sequence motif within the R1 element that binds a human
      cell nuclear protein which is antigenically related to the Drosophila boundary
      element-associated factor (BEAF). The potential role of a 35-kDa cellular protein
      that binds to sequence motifs within the R1 element in regulating the expression
      of the CMV US3 immune evasion gene is discussed.

PMID- 12009784
TI  - Expression of CD44v5 and -v6 in Barrett's carcinoma is not increased compared to
      that in nondysplastic Barrett's mucosa.
AB  - Barrett's adenocarcinoma currently shows the highest increase in the incidence of
      all malignant tumors. Reliable molecular markers to identify Barrett's patients
      at risk are still missing. Our own results demonstrate that the expression of
      CD44v6 correlates with the development of dysplasia in colorectal neoplasms.
      Therefore, we examined the expression of CD44 variants v5 and v6 in normal
      esophageal mucosa, non-dysplastic Barrett's mucosa, and Barrett's carcinoma. mRNA
      from biopsy specimens of patients with Barrett's esophagus (n = 19) or Barrett's
      carcinoma (n = 15) and patients without esophageal diseases (controls; n = 9)
      were extracted and used as templates for cDNA synthesis. CD44 variants were
      detected by RT-PCR with primers hybridizing with CD44 sequences up- and
      downstream of variable exons. CD44v6 expression was found in 36 of 56 biopsy
      specimens (64%) of non-dysplastic Barrett's mucosa, in 100% of squamous
      epithelium, and in none of the gastric mucosa specimens. Eleven of 15 specimens
      (73%) of Barrett's carcinoma tested positive for v6 expression. The
      identification of v5 expression did not give additional information. There was no
      correlation between CD44v5 or -v6 expression and staging or grading of the
      tumors. Expression of CD44v5 and -v6 seems to be independent of the development
      of cancer in Barrett's mucosa.

PMID- 12009785
TI  - Pulmonary pathologies in pallid mice result from nonhematopoietic defects.
AB  - Several single gene pigment mutants of inbred C57BL/6J mice display a triad of
      subcellular granule-associated defects: oculocutaneous pigment dilution,
      prolonged bleeding due to defects in platelet dense granules, and abnormal
      lysosomes. These features also characterize Hermansky-Pudlak Syndrome (HPS),
      making these mice relevant animal models for HPS. Mice of one mutant strain,
      pallid, in addition to the hallmark triad of signs, also exhibit age-dependent
      lung pathology. Respiratory system mechanics showed that the age-dependent
      histopathology of pallid mice was accompanied by a decrease in lung reactance.
      Furthermore, the possibility that pallid pulmonary pathology may result from
      persistent inflammation due to microhemorrhage owing to the platelet defect was
      examined. Hematopoietic reconstitution of pallid mice with marrow from normal
      C57BL/6J donors did not prevent the development of the pulmonary histopathology
      or respiratory system mechanics characteristic of the pallid genotype. Similarly,
      wild-type mice 12 months after engraftment with pallid marrow did not develop
      pallid-like pulmonary histopathology or respiratory system mechanics. Thus,
      pallid-associated pulmonary functional and structural pathologies are not linked
      to the marrow (bleeding) genotype, but instead are the result of an age-dependent
      process resulting from a defect(s) in one or more nonhematopoietic cell types.

PMID- 12009786
TI  - Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in
      vitro.
AB  - EC culture models are essential to study pathological alterations of endothelial
      cells (ECs) in pulmonary vascular diseases under standardized conditions.
      Nevertheless, little is known about the spectrum of alterations of vessel
      specific endothelial phenotypes in monolayer cultures. For the comparative study
      of endothelial markers in vivo and in vitro we investigated immunohistochemically
      the expression of PECAM-1, vWf, and CD34 by pulmonary ECs in vivo and in
      stimulated/unstimulated human umbilical vein endothelial cells (HU-VEC) and human
      pulmonary microvascular endothelial cells (HPMEC). In vivo, vessel type-specific
      expression patterns were found for vWf and CD34, while PECAM-1 was homogeneously
      and strongly expressed. While all HUVEC showed a marked vWf staining, about two
      thirds of HPMEC exhibited a strong and the rest a moderate vWf staining. In both
      in vitro models all ECs were clearly PECAM-1-positive. However, only about 20% of
      the HUVEC and HPMEC were CD34-positive. Our results demonstrate the reduced
      expression of vessel type-specific endothelial phenotypes by endothelial
      monolayer cultures, stressing the need to improve culture conditions as well as
      develop cocultures and three-dimensional culture models. Moreover, the need for
      endothelial markers specific for single microvascular type ECs becomes obvious in
      order to establish cultures consisting of only one microvascular ECs
      subpopulation.

PMID- 12009787
TI  - Regional variations in the distributions of small intestinal intraepithelial
      lymphocytes in germ-free and specific pathogen-free mice.
AB  - Previously, we reported the regional variations in intraepithelial lymphocytes
      (IELs) in the small intestine of mice. To clarify the effects of intestinal
      bacteria on the distribution of IELs, regional variations in IELs were examined
      using germ-free (GF) and specific pathogen-free (SPF) BALB/cA mice. The small
      intestine was taken and divided equally into three parts (the proximal, middle,
      and distal parts). IELs were isolated from each part of the intestine, and the
      total number of IELs in GF mice was about one seventh of that in SPF mice. The
      decreased number of IELs in GF mice suggests that intestinal bacteria may be
      essential for local expansion of IELs. On the other hand, similar regional
      variations in IEL subsets observed in both GF and SPF mice, except for some
      subsets. The similarity of regional variations in GF and SPF mice indicates that
      the regional variations in IEL subsets may not fundamentally depend on intestinal
      bacteria.

PMID- 12009788
TI  - Antilymphoproliferative activity of ethanolic extract of Boerhaavia diffusa
      roots.
AB  - Extracts of plants have been widely evaluated for possible antiproliferative and
      anticarcinogenic properties. The antiproliferative activity of ethanolic extract
      of Boerhaavia diffusa, a plant used in traditional medicine, was evaluated in
      several cells. It inhibited T cell mitogen phytohemagglutinin and concanavalin A
      stimulated proliferation of human peripheral blood mononuclear cells (PBMC). It
      also inhibited purified protein derivative antigen-stimulated PBMC proliferation
      and human mixed lymphocyte culture. In addition, B. diffusa extract inhibited the
      growth of several cell lines of mouse and human origin, such as mouse macrophage
      cells (RAW 264.7), human macrophage cells (U937), human monocytic cells (THP-1),
      mouse fibroblast cells (L929), human embryonic kidney cells (HEK293), mouse liver
      cells (BNLCL.2), African green monkey kidney cells (COS-1), mouse lymphoma cells
      (EL-4), human erythroleukemic cells (K562), and human T cells (Jurkat). The
      present study has demonstrated the antiproliferative potential of ethanolic
      extract of B. diffusa in vitro.

PMID- 12009791
TI  - The mathematics of metabolic control analysis revisited.
AB  - In this minireview, several different approaches to derivation of the theorems
      and relationships of Metabolic Control Analysis (MCA) are discussed and an
      alternative approach is presented. This new approach consists of solving the
      steady-state mass balances for the intracellular metabolites using linearized
      kinetics. The application of linearized kinetics reflects the fact that MCA is
      based on linearization of the system equations in a reference steady state. Our
      derivation is valid for metabolic networks of arbitrary complexity, including
      those containing conserved moieties and branches. The value of our approach is
      its simplicity: the derivation is straightforward and therefore easy to follow.
      It can serve as a compact introduction to the mathematical basis of MCA.

PMID- 12009792
TI  - Analysis of carbon metabolism in Escherichia coli strains with an inactive
      phosphotransferase system by (13)C labeling and NMR spectroscopy.
AB  - We have developed Escherichia coli strains that internalize glucose utilizing the
      GalP permease instead of the phosphoenolpyruvate:carbohydrate phosphotransferase
      system. It has been demonstrated that a strain with these modifications (PTS(
      )Glc(+)) can direct more carbon flux into the aromatic pathway than the wild-type
      parental strain (N. Flores et al., 1996, Nat. Biotechnol. 14, 620-623; G. Gosset
      et al., 1996, J. Ind. Microbiol. 17, 47-52; J. L. Baez et al., 2001, Biotechnol.
      Bioeng. 73, 530-535). In this study, we have determined and compared the carbon
      fluxes of a wild-type strain (JM101), a PTS(-)Glc(-) strain, and two isogenic
      PTS(-)Glc(+) derivatives named PB12 and PB13 by combining genetic, biochemical,
      and NMR approaches. It was determined that in these strains a functional glk gene
      in the chromosome is required for rapid glucose consumption; furthermore,
      glucokinase-specific activities were higher than in the wild-type strain. (13)C
      labeling and NMR analysis allowed the determination of differences in vivo which
      include higher glycolytic fluxes of 93.1 and 89.2% compared with the 76.6%
      obtained for the wild-type E. coli. In PB12 and PB13 we found a flux through the
      malic enzymes of 4 and 10%, respectively, compared to zero in the wild-type
      strain. While flux through the Pck enzyme was absent in PB12 and PB13, in the
      wild type it was 7.7%. Finally, it was found that in the JM101 and PB12 strains
      both the oxidative and the nonoxidative branches of the pentose phosphate pathway
      contributed to ribose 5-phosphate synthesis, whereas in PB13 this pentose was
      synthesized almost exclusively through the oxidative branch. The determined
      carbon fluxes correlate with biochemical and genetic characterizations.

PMID- 12009793
TI  - Carbon flux distribution in antibiotic-producing chemostat cultures of
      Streptomyces lividans.
AB  - The carbon metabolism of derivatives of Streptomyces lividans growing under
      phosphate limitation in chemostat cultures and producing the antibiotics
      actinorhodin and undecylprodigiosin was investigated. By applying metabolic flux
      analysis to a stoichiometric model, the relationship between antibiotic
      production, biomass accumulation, and carbon flux through the major carbon
      metabolic pathways (the Embden Meyerhoff Parnas and pentose-phosphate pathways)
      was analyzed. Distribution of carbon flux through the catabolic pathways was
      shown to be dependent on growth rate, as well as on the carbon and energy source
      (glucose or gluconate) used. Increasing growth rates promoted an increase in the
      flux of carbon through glycolysis and the pentose-phosphate pathway. The
      synthesis of both actinorhodin and undecylprodigiosin was found to be inversely
      related to flux through the pentose-phosphate pathway.

PMID- 12009794
TI  - Metabolic network analysis of an adipoyl-7-ADCA-producing strain of Penicillium
      chrysogenum: elucidation of adipate degradation.
AB  - An adipoyl-7-ADCA-producing, recombinant strain of Penicillium chrysogenum was
      characterized by metabolic network analysis, with special focus on the
      degradation of adipate and determination of the metabolic fluxes. Degradation of
      the side-chain precursor, adipate, causes an undesired consumption of adipate in
      the production of 7-ADCA. Using (13)C-labeled glucose and measurement of
      metabolite labeling patterns, it was shown that adipate was degraded by beta
      oxidation to succinyl-CoA and acetyl-CoA. The labeling analysis indicated that
      degradation of adipate was taking place in the microbodies and the formed acetyl
      CoA was metabolized in the glyoxylate shunt. This hypothesis was further
      substantiated by an enzyme assay, which showed activity of the key enzyme in the
      glyoxylate shunt. Flux estimations in two chemostat cultures, one with and one
      without adipate in the feed, revealed that degradation of adipate replaces the
      net anaplerotic reaction from pyruvate to oxaloacetate. Thus, with a combination
      of labeling experiments and enzyme assays, the pathway of adipate degradation was
      elucidated, and the effect of adipate degradation on the primary metabolism was
      quantified.

PMID- 12009795
TI  - Metabolic network analysis of Bacillus clausii on minimal and semirich medium
      using (13)C-labeled glucose.
AB  - Using (13)C-labeled glucose fed to the facultative alkalophilic Bacillus clausii
      producing the alkaline serine protease Savinase, the intracellular fluxes were
      quantified in continuous cultivation and in batch cultivation on a minimal
      medium. The flux through the pentose phosphate pathway was found to increase with
      increasing specific growth rate but at a much lower level than previously
      reported for Bacillus subtilis. Two futile cycles in the pyruvate metabolism were
      included in the metabolic network. A substantial flux in the futile cycle
      involving malic enzyme was estimated, whereas only a very small or zero flux
      through PEP carboxykinase was estimated, indicating that the latter enzyme was
      not active during growth on glucose. The uptake of the amino acids in a semirich
      medium containing 15 of the 20 amino acids normally present in proteins was
      estimated using fully labeled glucose in batch cultivations. It was found that
      leucine, isoleucine, and phenylalanine were taken up from the medium and not
      synthesized de novo from glucose. In contrast, serine and threonine were
      completely synthesized from other metabolites and not taken up from the medium.
      Valine, proline, and lysine were partly taken up from the medium and partly
      synthesized from glucose. The metabolic network analysis was extended to include
      analysis of growth on the semirich medium containing amino acids, and the
      metabolic flux distribution on this medium was estimated and compared with growth
      on minimal medium.

PMID- 12009796
TI  - A general method for determining the contribution of split pathways in metabolite
      production in the yeast Saccharomyces cerevisiae.
AB  - We describe a simple method using (13)C labeling and NMR spectroscopy to
      determine the flux contributions of alternative pathways in Saccharomyces
      cerevisiae that produce the same metabolite with identical labeling patterns.
      Cells were incubated with a (13)C-labeled precursor for one of the branches, and
      the absolute enrichment of the product and its metabolic precursor(s) was
      quantified. The ratio of the absolute enrichment of the product to that of its
      precursor reflects the contribution of the pathway. The method was applied to the
      biosynthesis of glycine in yeast, which can occur from threonine via threonine
      aldolase or from serine via serine hydroxymethyltransferase. [2-(13)C]Aspartate
      and [2-(13)C]serine were used as labeled precursors for the threonine aldolase
      and serine hydroxymethyltransferase pathways, respectively. The data show that in
      cells possessing both pathways, the serine hydroxymethyltransferase pathway
      contributes 65-75% of the total glycine production. In comparison with other
      approaches, this method provides an inexpensive, flexible alternative to
      determining the flux contributions of split pathways under controlled conditions
      and should have wide applicability in the metabolic engineering of
      microorganisms.

PMID- 12009797
TI  - Metabolic engineering through cofactor manipulation and its effects on metabolic
      flux redistribution in Escherichia coli.
AB  - Applications of genetic engineering or metabolic engineering have increased in
      both academic and industrial institutions. Most current metabolic engineering
      studies have focused on enzyme levels and on the effect of the amplification,
      addition, or deletion of a particular pathway. Although it is generally known
      that cofactors play a major role in the production of different fermentation
      products, their role has not been thoroughly and systematically studied. It is
      conceivable that in cofactor-dependent production systems, cofactor availability
      and the proportion of cofactor in the active form may play an important role in
      dictating the overall process yield. Hence, the manipulation of these cofactor
      levels may be crucial in order to further increase production. We have
      demonstrated that manipulation of cofactors can be achieved by external and
      genetic means and these manipulations have the potential to be used as an
      additional tool to achieve desired metabolic goals. We have shown experimentally
      that the NADH/NAD(+) ratio can be altered by using carbon sources with different
      oxidation states. We have shown further that the metabolite distribution can be
      influenced by a change in the NADH/NAD(+) ratio as mediated by the oxidation
      state of the carbon source used. We have also demonstrated that the total
      NAD(H/(+)) levels can be increased by the overexpression of the pncB gene. The
      increase in the total NAD(H/(+)) levels can be achieved even in a complex medium,
      which is commonly used by most industrial processes. Finally, we have shown that
      manipulation of the CoA pool/flux can be used to increase the productivity of a
      model product, isoamyl acetate.

PMID- 12009798
TI  - Genetic evidence for coinfection of honey bees by acute bee paralysis and Kashmir
      bee viruses.
AB  - Nucleotide sequence analyses were used to identify acute bee paralysis virus
      (ABPV) and Kashmir bee virus (KBV) isolated from a single honey bee colony. Most
      of the bees in this colony carried KBV. Some individual bees also carried ABPV, a
      coexistence not yet seen between these two viruses. Implications of coinfection
      on viral efficacy are discussed, along with a restriction enzyme assay that can
      be used to discriminate between these two widespread viruses.

PMID- 12009799
TI  - Ultrastructural aspects of a new species, Vavraia mediterranica (Microsporidia,
      Pleistophoridae), parasite of the French Mediterranean shrimp, Crangon crangon
      (Crustacea, Decapoda).
AB  - The life cycle stages of a new species of the genus Vavraia (Microsporidia,
      Pleistophoridae), which parasitizes the shrimp Crangon crangon (Crustacea,
      Decapoda), were examined by light and electron microscopy. This parasite was
      monomorphic with polysporous sporogony and developed in the skeletal muscle of
      the host. The multinucleate sporogonial plasmodium divided by plasmotomy and
      multiple division into uninucleate sporoblasts. All stages were surrounded by a
      thick and amorphous dense coat external to the plasmalemma. This structure
      gradually became a merontogenetic sporophorous vacuole (MSV) where the sporonts
      developed into sporoblasts. The MSV was filled with episporontal granular
      secretory products and eventually contained up to 50 uninucleate spores. During
      spore morphogenesis, these episporontal granular products within the MSV became
      organized as episporontal tubular-like structures. In transverse sections, these
      structures showed a mean diameter of 1.0 microm, but disappeared during the final
      phase of the spore maturation. Mature spores were ellipsoidal to slightly
      pyriform and measured 2.30 x 1.41 microm. The polar filament was anisofilar and
      consisted of a single coil with six to seven turns (rarely five). This new
      species is named Vavraia mediterranica n. sp.

PMID- 12009800
TI  - Survival and differential development of Entomophaga maimaiga and Entomophaga
      aulicae (Zygomycetes: Entomophthorales) in Lymantria dispar hemolymph.
AB  - The closely related entomophthoralean fungi Entomophaga aulicae and E. maimaiga
      are both host-specific pathogens of lepidopteran larvae. However, these fungi do
      not have the same host range. The first objective of this study was to compare
      the fate of E. aulicae in the nonpermissive host Lymantria dispar with the fate
      of the successful pathogen E. maimaiga over the same time period. In the
      hemolymph of L. dispar injected with E. maimaiga protoplasts, the number of
      hemocytes demonstrated a decreasing trend after the first day postinjection and
      hemocytes completely disappeared by day 5, with the majority of larvae dying in
      5.6 +/- 0.1 days. In L. dispar larvae, E. maimaiga infections developed
      successfully, evidenced by increasing numbers of protoplasts and hyphal bodies
      prior to host mortality. In contrast, at day 5 hemocytes were readily visible in
      hemolymph of E. aulicae-injected larvae, but E. aulicae cells did not increase in
      numbers, although persisting in the hemolymph for at least 16 days postinjection.
      For both fungal species, when hemolymph samples from injected insects were
      introduced to culture media viable fungal cultures were always produced. Both E.
      aulicae and E. maimaiga occurred in hemolymph initially after injection as
      protoplasts. For E. maimaiga, after day 3, <50% of fungal cells were hyphal
      bodies until insect death when most cells regenerated cell walls. For E. aulicae,
      from day 2 equal numbers of fungal cells in the hemolymph occurred as protoplasts
      and hyphal bodies. To investigate the cause of fungistasis in E. aulicae-injected
      larvae, E. aulicae cell cultures exposed to partially purified protein fractions
      from hemolymph of larvae infected with either fungus displayed increased lysis
      and decreased viability at lower concentrations of protein fractions compared
      with E. maimaiga cell cultures. These studies demonstrate that E. aulicae does
      not increase in L. dispar hemolymph, although it persists and results suggest
      that proteinaceous factors induced within the hemolymph may limit the capacity of
      E. aulicae to develop successful infections.

PMID- 12009801
TI  - Interaction of Nosema pyrausta and temperature on Ostrinia nubilalis egg
      production and hatch.
AB  - Nosema pyrausta is an obligate pathogen causing reduced fecundity and longevity
      of Ostrinia nubilalis. This study was conducted to determine the combined effects
      of N. pyrausta infection and temperature on O. nubilalis egg production and
      hatch. N. pyrausta-infected and noninfected O. nubilalis were maintained in two
      different temperature regimes. The first regime allowed females to oviposit under
      optimum conditions (27 degrees C, 65% RH, 16:8 (L:D)), while females in the
      second regime were held initially under the same humidity and light conditions,
      but a constant temperature of 16 degrees C for 1 week after which they were
      transferred to optimum ovipositional conditions. Studies were performed initially
      with O. nubilalis populations and later with individual mating pairs. In studies
      with O. nubilalis populations, the mean number of eggs laid per female under
      optimum conditions was 660, while N. pyrausta-infected females held initially at
      16 degrees C laid 116 eggs per female. In studies with individual mating pairs,
      N. pyrausta infection reduced egg production per female 53 and 11% in the 16 and
      27 degrees C temperature regimes, respectively, compared to noninfected females
      under optimum conditions. Exposure to 16 degrees C temperatures early in the
      ovipositional period had a more profound impact on reducing egg production in N.
      pyrausta-infected than noninfected O. nubilalis.

PMID- 12009802
TI  - Differences in the susceptibility of American white shrimp larval substages
      (Litopenaeus vannamei) to four vibrio species.
AB  - The rapid expansion of commercial culture of penaeid shrimp is threatened by
      Vibrio diseases affecting survival and growth. These opportunistic microorganisms
      are considered part of the normal ecosystem of penaeid shrimp and cause diseases
      only under conditions that favor them over the host. Shrimp larvae show different
      susceptibility to these pathogenic agents. In the present work, we report on a
      comparative study of the susceptibility of all American white shrimp (Litopenaeus
      vannamei) larval substages to four potentially pathogenic Vibrio species (V.
      harveyi, V. parahaemolyticus, V. alginolyticus, and V. penaeicida). Strains of
      these bacterial species were used to infect nauplii, protozoea I-III, mysis I
      III, and postlarvae 1 by immersion challenge at 10(3), 10(5), or 10(7) cfu mL(-1)
      for 30 min. V. alginolyticus infection had no significant effect on survival
      rate, compared to control, in all shrimp larvae and at all doses tested. Shrimp
      larvae infected with V. alginolyticus showed a high survival rate compared to
      other Vibrio species at the three dose levels. V. penaeicida produced a
      significant mortality effect (P < 0.01) in all shrimp substages and only in
      postlarvae 1 at low infection dose (10(3) cfu mL(-1)). V. harveyi and V.
      parahaemolyticus induced significant mortality rates (P < 0.01) only at high
      doses in shrimp larvae. In summary, shrimp larvae demonstrated an age
      susceptibility that depends on the Vibrio species and dose level.

PMID- 12009803
TI  - Discovering new insect viruses: whitefly iridovirus (Homoptera: Aleyrodidae:
      Bemisia tabaci).
AB  - Adult whiteflies, Bemisia tabaci (Gennadius), collected from the field were
      screened for viral pathogens using a cell line from the silverleaf whitefly, B.
      tabaci, B biotype (syn. B. argentifolii). Homogenates from the field-collected
      whiteflies were applied to cell cultures and checked for cytopathic effects
      (CPE). Cells were observed to develop cytoplasmic inclusions and to have a change
      in morphology. Cells displaying CPE were observed using a transmission electron
      microscope and found to be infected with a virus. The virus particles had an
      icosahedral shape and an approximate size of 120-130 nm. The virus was observed
      in defined areas of the cytoplasm adjacent to the cell nucleus. Analysis using
      polymerase chain reaction, Southern blot hybridization, and DNA sequencing
      confirmed that the virus discovered infecting the whitefly cell cultures was an
      iridovirus. Sequence analysis showed that the amplimer (893 bp) had a 95%
      homology to the invertebrate iridescent virus type 6 major capsid protein gene.
      Discovery of new viruses of whiteflies may provide renewed interest in using
      pathogens in the development of innovative management strategies. This is the
      first report of an iridescent virus isolated from whiteflies, B. tabaci,
      collected from the field.

PMID- 12009804
TI  - Natural occurrence of entomophthoralean fungi pathogenic to collembolans.
AB  - The aim of this study was to assess the natural occurrence of fungi from the
      order Entomophthorales (Zygomycetes) pathogenic to a range of collembolan
      species. A total of 11,709 collembolans representing a total of 15 species from
      all three subclasses within Collembola were collected and incubated. Infection
      with Neozygites-like spp. (Entomophthorales) was recorded in the two subclasses,
      Arthropleona and Symphypleona. The morphology of the primary conidia of the
      Neozygites-like fungi infecting collembolans showed a high degree of variation in
      shape and size, and the fungi were divisible into five groups. One group
      consisted of Neozygites sminthuri, while the other four groups, while still
      closely resembling the genus Neozygites, did not fit within the description of
      any known species and were preliminarily designated Neozygites sp. nov. 1 to 4.
      Neozygites sp. nov. 1, infecting Sphaeridia pumilis, was observed to form
      globular secondary conidia, which have not been observed before within the genus
      Neozygites. A formal species description needs, however, yet to be performed. The
      infection was mainly found in species from the subclass Symphypleona, where two
      new host genera for Neozygites, Deuterosminthurus and Sphaeridia, were recorded.
      However, the prevalence of Neozygites spp. was low, up to 10% in S. pumilis, 6%
      in Sminthurus viridis, and below 1% in Deuterosminthurus sulphureus. Infection
      with an obligatory entomopathogenic fungus was for the first time well documented
      within the subclass Arthropleona, where specimens of Orchesella cincta and
      Orchesella villosa sporulated with a N. sminthuri-like fungus. Additionally,
      infection with the facultative pathogen Conidiobolus coronatus was recorded from
      several hosts representing both the subclass Arthropleona (Isotoma anglicana and
      O. cincta) and the subclass Symphypleona (Dicyrtoma sp. and S. viridis). For most
      species the prevalence of C. coronatus resembled that of Neozygites spp. and did
      not exceed 8.8%. The only exception was Dicyrtoma sp., for which the only
      associated entomophthoralean fungus was C. coronatus, where the prevalence
      reached 17.8% infection.

PMID- 12009805
TI  - Pathobiology of amber disease, caused by Serratia Spp., in the New Zealand grass
      grub, Costelytra zealandica.
AB  - Amber disease in the New Zealand grass grub (Costelytra zealandica) is caused by
      some strains of Serratia entomophila or Serratia proteamaculans
      (Enterobacteriaceae). When treated with pathogenic isolates, larvae ceased
      feeding within 48 h, developed an amber coloration after 72 h, and entered a long
      chronic phase without feeding. An acute dose of 2-4 x 10(4) pathogenic bacteria
      was sufficient to produce disease in 50% of treated larvae. Time to death was
      directly related to temperature. At 15 degrees C, infected larvae remained in a
      chronic, nonfeeding state for more than 4 months prior to death. Nonpathogenic
      isolates, lacking the disease-causing plasmid (pADAP), had no effect on either
      feeding or disease. Twenty-four hours after ingestion, bacteria were found
      predominantly in the hindgut and growth occurred primarily within the
      fermentation chamber and in the head section of the larvae. Nonpathogenic strains
      did not multiply in treated larvae. Treatment of diseased larvae with antibiotic
      eliminated Serratia cells from the insects but did not result in restoration of
      feeding or the dark gut characteristic of the healthy larva.

PMID- 12009806
TI  - Impact of a North American isolate of the microsporidium Nosema carpocapsae on a
      laboratory population of the codling moth, Cydia pomonella.
AB  - Nosema carpocapsae is a microsporidian pathogen of the codling moth, Cydia
      pomonella. We report the occurrence of this pathogen in a colony originating from
      collections made in the United States. This is the first record of N. carpocapsae
      infecting North American codling moths. This North American isolate of N.
      carpocapsae was indistinguishable from isolates received from New Zealand and
      Bulgaria, based on small subunit ribosomal RNA sequencing, but was more virulent
      than the previously described New Zealand isolate. In the laboratory, infected
      larvae and pupae had increased mortality compared to their uninfected
      counterparts and developmental time increased by 1 week. There was no effect on
      female fecundity. Within a cohort of eggs laid by infected females, neonates that
      emerged first were more likely to be uninfected. We established an uninfected
      colony by interrupting horizontal transmission and only utilizing the larvae that
      emerged from the first-laid eggs.

PMID- 12009807
TI  - Intraspecific variation and host specificity of Entomophthora muscae sensu
      stricto isolates revealed by random amplified polymorphic DNA, universal primed
      PCR, PCR-restriction fragment length polymorphism, and conidial morphology.
AB  - The intraspecific variations of Entomophthora muscae s. str. associated with
      particular host species, Musca domestica and Delia radicum, sampled from
      different localities and different years in Denmark and the variation of E.
      muscae s. str. originating from different host taxa were investigated. The
      isolates were compared both by primary spore morphology and by three molecular
      methods: random amplified polymorphic DNA, universal primed PCR, and PCR
      restriction fragment length polymorphism. Analyses of the different molecular
      data showed the same overall picture and separated E. muscae s. str. into two
      main groups with all the M. domestica isolates in one group and isolates from D.
      radicum, Coenosia tigrina, and Pegoplata infirma in the second group. E. muscae
      s. str. isolates from M. domestica also differ significantly from the rest of the
      E. muscae s. str. isolates with regard to the morphology of the primary conidia,
      which were bigger and contained significantly more nuclei per conidium. Several
      different E. muscae s. str. genotypes were documented and each type was
      restricted to a single host species, indicating a very high degree of host
      specificity at or below the level of the subfamily.

PMID- 12009809
TI  - How does infection with parthenogenesis-inducing Wolbachia reduce the fitness of
      Trichogramma?
AB  - We analyzed the survival rate of the immature stages of Trichogramma species and
      lines that differed in their mode of reproduction. Specifically, we compared the
      mortality of arrhenotokous (W(-)), irrevertable thelytokous (W(-)), and Wolbachia
      associated thelytokous (W(+)) forms. The embryonic mortality of the W(+) strains
      was significantly higher than that of the W(-) lines. The embryonic mortality was
      negligible for the arrhenotokous Trichogramma evanescens and the thelytokous
      Trichogramma cacoeciae, which is not infected with Wolbachia. Only 30% of the
      eggs of the Wolbachia-infected strains developed to adults, while the emergence
      rate of the Wolbachia-free strains was more than 78%, irrespective of the origin
      of the strains. More than 78% of the overall mortality in W(+) strains happened
      during the early stages of development. About 35% of embryos of W(+) strains
      remain in the mitotic stage even 48 h after oviposition. Most embryos of W(-)
      strains had already developed to cellular blastoderm after 6 h, regardless of
      strains. The mortality of immature stages in W(+) strains was mainly caused by
      the failure of the mitotic divisions.

PMID- 12009808
TI  - Transformants of Metarhizium anisopliae sf. anisopliae overexpressing chitinase
      from Metarhizium anisopliae sf. acridum show early induction of native chitinase
      but are not altered in pathogenicity to Manduca sexta.
AB  - Extracellular chitinase activity has been implicated in the pathogenesis of
      several fungal infections. Following induction with chitin, the insect pathogens
      Metarhizium anisopliae sf. acridum ARSEF strain 324 and Metarhizium anisopliae
      sf. anisopliae ARSEF strain 2575 secrete 44-kDa basic and acidic isoforms of
      endochitinase, respectively. The gene from strain 324 (Chit1) was cloned and
      inserted into the genome of strain 2575 under the control of Aspergillus
      regulatory elements such that transgenic 2575 (2575-Chit(+)) expressed CHIT1 in a
      noninducing medium (i.e., not containing chitin). Isoelectric focusing followed
      by a zymogram technique revealed that neither wild-type 2575 nor 2575-Chit(+)
      produced significant amounts of the native 2575 acidic chitinase in a noninducing
      medium. However, in a chitin-containing medium, 2575-Chit(+) produced the native
      chitinase earlier than strain 2575, soon after secretion of CHIT1. We hypothesize
      that this is due to the production of soluble inducers following chitin
      hydrolysis by CHIT1 and that M. anisopliae uses enzymes expressed at low levels
      to sense the nature of the polymeric nutrient present in the immediate
      environment. However, the chitinase overproducers did not show altered virulence
      to caterpillars (Manduca sexta) compared to the wild-type fungus, suggesting that
      wild-type levels of chitinase are not limiting for cuticle penetration.

PMID- 12009810
TI  - Encapsulation response of 6th instar of Pseudaletia unipuncta (Lepidoptera:
      Noctuidae) to Steinernema carpocapsae (Nematoda: Steinernematidae).

PMID- 12009811
TI  - Comparison of different methodologies for binding assays of Bacillus
      thuringiensis toxins to membrane vesicles from insect midguts.

PMID- 12009812
TI  - Pulsed-field gel electrophoresis for the identification of bacteria causing milky
      disease in scarab larvae.

PMID- 12009813
TI  - The organization of hospital infection control in Turkey.
AB  - This article describes the current organization of infection control in Turkey in
      regard to regulations, functions and responsibilities of infection control
      committees and the national NosoLINE project. Also, incidence and prevalence of
      hospital infections and antimicrobial resistance in Turkey are reported.

PMID- 12009814
TI  - Rinse water for heat labile endoscopy equipment.
AB  - The increase in use of endoscopic procedures in diagnosis and surgical treatment
      has underlined the need for safe cleaning methods for these instruments. While
      decontamination has been reviewed by several Working Groups in Britain, the
      problems relating to the prevention of contamination of rinse water and its
      monitoring procedures have not been addressed previously. This report from the
      Joint Working Party identifies the problems, and provides guidance on the
      monitoring and provision of high-quality rinse water.

PMID- 12009815
TI  - Hospital Infection Society/Association of Medical Microbiologists "Towards a
      Consensus II"' Workshop I. Hospital-acquired infection and risk management.

PMID- 12009816
TI  - Management of an outbreak of Enterobacter cloacae in a neonatal unit using simple
      preventive measures.
AB  - Enterobacter cloacae is becoming an increasingly important nosocomial pathogen.
      Outbreaks of E. cloacae in intensive care units and burns units have been
      described frequently. In December 1999, a neonate with line sepsis was
      transferred from a university hospital to the neonatal unit of the Diakonessen
      Hospital. Blood culture yielded E. cloacae. An outbreak of E. cloacae was
      occurring in the university hospital at that time. In February 2000, a second
      neonate in our hospital developed line sepsis caused by E. cloacae. Direct
      measures taken included cohorting of infected children, disinfection of
      incubators, thermometers and wards, and screening patients. Of nine neonates,
      seven were colonized with E. cloacae. Despite these measures, the outbreak
      continued. Forty-one patients were screened; 15 were colonized. Environmental
      searches yielded E. cloacae in a sink and on two thermometers. Sixteen isolates
      were typed by arbitrarily primed PCR using four primers. All the patient isolates
      and the two isolates from thermometers were identical. The strain isolated from
      the sink was unrelated. Amplified fragment length polymorphism typing showed that
      the outbreak clone was identical to that in the university hospital. After the
      introduction of disposable thermometer covers, E. cloacae colonization slowly
      decreased.

PMID- 12009817
TI  - Molecular epidemiology of nosocomial infection associated with multi-resistant
      Acinetobacter baumannii by infrequent-restriction-site PCR.
AB  - Acinetobacter baumannii was considered endemic in a university-affiliated
      tertiary hospital. A significant increase was noted in the proportion of
      nosocomial infections associated with this micro-organism from 1996 to 1999,
      although no apparent clusters could be found. Between July 1998 and February
      2000, 58 nosocomial isolates of A. baumannii were collected and characterized by
      antibiotyping and a genotyping method, infrequent-restriction-site PCR (IRS-PCR).
      High resistance to the 14 antimicrobial agents examined was observed among the
      isolates. Of the 13 antibiograms detected, eight were multi-resistant to
      gentamicin and almost all of the traditional and extended-spectrum beta-lactams.
      These multi-resistant strains consisted of 41 isolates (71%), distributed amongst
      different wards and intensive care units (ICUs). By IRS-PCR, 23 types were
      obtained, with one major type found among 28 (48%) isolates. All of these 28
      isolates were collected from surgical ICUs. It appears that a single strain of
      multi-resistant A. baumannii was responsible for the prevalence of nosocomial
      infection amongst surgical patients, clearly differentiating this outbreak from
      the previous endemic situation. An efficient molecular typing method played a
      vital role in making this discrimination.

PMID- 12009818
TI  - Molecular epidemiology of coagulase-negative staphylococcal bacteraemia in a
      newborn intensive care unit.
AB  - We isolated 55 coagulase-negative staphylococci (CoNS) over two separate 12-month
      periods (26 in 1993 and 29 in 1996) from the blood of neonates in a neonatal
      intensive case unit (NICU) in Melbourne, Australia and compared them by pulse
      field gel electrophoresis profile (PFGE), random amplification of polymorphic DNA
      (RAPD) and antibiogram. The most common species were Staphylococcus epidermidis,
      S. haemolyticus and S. warneri. The majority of such isolates were resistant to
      penicillin and to either or both of methicillin and gentamicin. During 1993,
      there was an increase in the number of CoNS bloodstream infections compared with
      previous years. S. epidermidis was the most common isolate, with 88% assessed as
      clinically relevant. Using the three typing systems, we identified one likely
      epidemic clone of S. epidermidis, the isolates of which were resistant to
      penicillin, gentamicin and erythromycin and possessed the mecA gene. There was
      complete correlation between the detection of mecA and the phenotypic expression
      of resistance when zone diameters in the disc diffusion assay were interpreted
      according to the latest NCCLS guidelines (1999). Profiles of the remaining 1993
      isolates were generally heterogeneous, suggesting independent acquisition with
      some evidence of cross-infection. The predominant bloodstream isolates in 1996
      were heterogeneous multi-resistant strains of S. epidermidis, S. haemolyticus and
      S. warneri, about half of which were assessed as clinically relevant. These data
      support the view that CoNS are significant nosocomial pathogens in NICU and that
      resistant clones may be transmitted between babies. Molecular epidemiological
      tools are helpful for understanding transmission patterns and sources of
      infection, and are useful for measuring outcomes of intervention strategies
      implemented to reduce nosocomial CoNS sepsis. PFGE was found to be more
      discriminatory than RAPD, but the latter provides results in a more timely
      manner.

PMID- 12009819
TI  - Prevalence of methicillin-resistant Staphylococcus aureus colonization in
      surgical patients, on admission to a Welsh hospital.
AB  - Nosocomial infection with methicillin-resistant Staphylococcus aureus (MRSA) is
      on the increase and expensive to treat. Because surgical wound infection is one
      of the most frequent MRSA-induced infections with often disastrous consequences,
      it was decided to estimate the incidence and risk factors of MRSA colonization in
      surgical patients. All patients admitted to general surgical and orthopaedic
      wards were studied prospectively. At the time of admission, a detailed
      questionnaire was completed, nasal swabs and swabs of any pre-existing wound
      sites in each patient were sent for culture. Of 430 patients studied, 23 patients
      were positive for MRSA on admission. The prevalence of MRSA colonization in this
      study was 5.3% of whom 15 (65%) were nasal carriers and eight (35%) had MRSA
      colonization elsewhere. All nasal MRSA carriers had at least one documented
      hospital admission in the preceding year. Among the MRSA-positive patients, 10
      (43%) either were admitted directly from, or had been previously admitted to, a
      nursing home. MRSA remains mainly a hospital-acquired infection although a
      significant proportion is acquired in the community. The risk factors identified
      were previous hospital admission, patients from nursing homes, male and aged over
      70.

PMID- 12009820
TI  - Hospital-acquired infections following the 1999 Marmara earthquake.
AB  - In this study, medical records of all casualties admitted to our hospital
      following the Marmara earthquake, which struck northwest Turkey and resulted in
      the destruction of several towns in the Marmara region, were evaluated
      retrospectively. The time buried under the rubble, demographic data, type of
      medical and surgical therapies performed, type of injury and data on infection
      were analysed. Between 17 August and 25 September 1999, 630 trauma victims were
      received at our hospital and 532 (84%) of them were hospitalized. The mean age of
      hospitalized patients (312 males, 220 females) was 32 years (2-90 years). Two
      hundred and twenty patients were hospitalized for more than 48 h. Forty-one of
      them (18.6%) had 43 hospital-acquired infection (HAI) episodes, which were mostly
      wound infections (46.5%). A total of 143 culture specimens was collected and 48
      yielded the following potential pathogens: 15 Acinetobacter baumanii (31.2%),
      nine Staphylococcus aureus (18.7%), seven Pseudomonas aeruginosa (14.6%), six
      Escherichia coli (12.5%), six Klebsiella pneumoniae (12.5%), two Stenotrophomonas
      maltophilia (4.2%) and three various Pseudomonas spp. (6.3%). All S. aureus
      strains were found to be resistant to methicillin in vitro. Two strains of A.
      baumannii and one P. aeruginosa were found to be resistant to all antimicrobials
      including carbapenems. Fifty-three victims died (10%) and 36 of those died during
      the first 48 h because of severe injuries and multi-organ failure. After 48 h of
      hospitalization, the mortality rate was significantly higher in those patients
      with HAI (14/41) than those without (3/179) (34.1% vs. 1.7%, P<0.05). In
      conclusion, trauma is the significant factor associated with HAI and a high
      incidence of Acinetobacter strains was responsible for HAI in trauma patients.

PMID- 12009821
TI  - Effectiveness of a multifaceted infection control policy in reducing vancomycin
      usage and vancomycin-resistant enterococci at a tertiary care cancer centre.
AB  - We undertook a prospective cohort study to evaluate the role of a multifaceted
      infection control policy including the use of a "vancomycin order form," in
      decreasing the transmission of vancomycin-resistant enterococci (VRE). In January
      1997, a multifaceted infection-control policy was implemented amongst patients
      admitted to the M. D. Anderson Cancer Center in whom neutropenic fever developed
      or who were found to be colonized or infected with VRE. As part of this
      programme, we initiated the use of a vancomycin order form to reduce the use of
      empirical vancomycin. The total incidence of VRE infections declined from
      0.437/1000 patient days in 1996-97 to 0.229/1000 patient days in 1998-99
      (P=0.008). The VRE bloodstream infections declined from 0.338/1000 patient days
      in 1996-97 to 0.181/1000 patient days in 1998-99 (P=0.027). Empiric vancomycin
      use decreased from 416 g/1000 patient days in 1996-97 to 208 g/1000 patient days
      in 1998-99 (P<0.001), resulting in a decreased vancomycin cost from $2561 US
      dollars/1000 patient days in 1996-97 to $1195 US dollars/1000 patient days in
      1997-98 (P<0.001). We conclude that a multifaceted infection control policy
      incorporating the use of a vancomycin order form can effectively decrease the use
      of empirical vancomycin and can play a role in limiting the spread of VRE in an
      endemic setting.

PMID- 12009822
TI  - Coronavirus-related nosocomial viral respiratory infections in a neonatal and
      paediatric intensive care unit: a prospective study.
AB  - The incidence of nosocomial viral respiratory infections (NVRI) in neonates and
      children hospitalized in paediatric and neonatal intensive care units (PNICU) is
      unknown. Human coronaviruses (HCoV) have been implicated in NVRI in hospitalized
      preterm neonates. The objectives of this study were to determine the incidence of
      HCoV-related NVRI in neonates and children hospitalized in a PNICU and the
      prevalence of viral respiratory tract infections in staff. All neonates (age< or
      =28 days) and children (age>28 days) hospitalized between November 1997 and April
      1998 were included. Nasal samples were obtained by cytological brush at admission
      and weekly thereafter. Nasal samples were taken monthly from staff. Virological
      studies were performed, using indirect immunofluorescence, for HCoV strains 229E
      and OC43, respiratory syncytial virus (RSV), influenza virus types A and B,
      paramyxoviruses types 1, 2 and 3 and adenovirus. A total of 120 patients were
      enrolled (64 neonates and 56 children). Twenty-two samples from 20 patients were
      positive (incidence 16.7%). In neonates, seven positive samples, all for HCoV,
      were detected (incidence 11%). Risk factors for NVRI in neonates were: duration
      of hospitalization, antibiotic treatment and duration of parenteral nutrition
      (P<0.01). Monthly prevalence of viral infections in staff was between 0% and
      10.5%, mainly with HCoV. In children, 15 samples were positive in 13 children at
      admission (seven RSV, five influenza and three adenovirus) but no NVRI were
      observed. In spite of a high rate of community-acquired infection in hospitalized
      children, the incidence of NVRI with common respiratory viruses appears low in
      neonates, HCoV being the most important pathogen of NRVI in neonates during this
      study period. Further research is needed to evaluate the long-term impact on
      pulmonary function.

PMID- 12009823
TI  - Nosocomial contamination by Mycobacterium gordonae in hospital water supply and
      super-oxidized water.
AB  - We experienced contamination by Mycobacterium gordonae of the hospital water of
      our surgical ward. The contamination was discovered following detection of the
      organism in operative lung samples, washed with super-oxidized water. Repeated
      examination of water demonstrated contamination by M. gordonae occurred only in
      the surgical ward, related to the apparatus for making super-oxidized water. No
      patients were infected by M. gordonae. After changing the water supply equipment
      and cleaning the water tubes, M. gordonae in the water disappeared.

PMID- 12009824
TI  - Impact of teaching interventions on nurse compliance with hand disinfection.
AB  - The impact of teaching interventions and the availability of additional
      dispensers for alcoholic hand disinfection was measured during three study
      periods. A nursing care system of relevant nursing interventions was found to be
      a useful tool for the assessment of compliance with hand hygiene requirements if
      combined with an analysis of hand disinfectant use. This study shows that
      compliance with hand disinfection can be improved through targeted teaching and
      supportive structural improvements, and that this positive impact may persist
      even after targeted teaching activities have ended.

PMID- 12009825
TI  - Continuing professional development and the Journal of Hospital Infection.

PMID- 12009826
TI  - MRSA decontamination of paper-containing objects.

PMID- 12009827
TI  - Turning a "blind eye" to vertical blinds in hospital wards.

PMID- 12009828
TI  - A case of central-venous-catheter-associated infection caused by Pichia ohmeri.

PMID- 12009829
TI  - Could an effervescent tablet, prepared with contaminated [correction of
      contamined] water, create an aerosol containing Legionella?

PMID- 12009842
TI  - Hypotensive properties and acute toxicity of trans
      [Ru(NH(3))(4)P(OEt)(3)(NO)](PF(6))(3), a new nitric oxide donor.
AB  - The hypotensive effect and the acute toxicity of trans
      [Ru(NH(3))(4)P(OEt)(3)(NO)](PF(6))(3) (RuNO) were investigated in conscious
      animals. The approximate lethal dose of RuNO is 257.5 micromol/kg in mice i.p.
      and the IC(50) values evaluated for V79 culture cell cytotoxicity were higher
      than 2.0 mM, suggesting that the ruthenium species are significantly less toxic
      than Na(2)[Fe(CN)(5)(NO)] (SNP) species. The RuNO hypotensive effect measured
      through in-bolus intravenous administration in chronically instrumented
      normotensive and hypotensive adult male Wistar rats is similar to that exhibited
      by equivalent doses of SNP. The hypotensive effect of the ruthenium complex is
      fully inhibited by methylene blue and PTIO, suggesting that the RuNO effect is
      likely to be primarily dependent on the NO-[cGMP] pathway in the smooth muscle
      cells.

PMID- 12009843
TI  - Role of Ca(2+)-independent phospholipase A(2) and cyclooxygenase/lipoxygenase
      pathways in the nitric oxide production by murine macrophages stimulated by
      lipopolysaccharides.
AB  - There is evidence of molecular cross talk between inflammatory mediators such as
      nitric oxide (NO) and prostaglandins (PG), which may regulate tissue homeostasis
      and contribute to pathophysiological processes. Here we examine the role of
      endogenous arachidonic acid (AA) and its AA metabolites in the regulation of NO
      release by lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. Our results
      suggest that bromoenol lactone-sensitive phospholipase A(2) is involved in AA
      release and the subsequent PG and leukotriene (LT) production. The cyclooxygenase
      inhibitor, indomethacin, and lipoxygenase inhibitors such as baicalein and
      zileuton blocked the dose-dependent PGE(2) or LTB(4) and nitrite (NO(2)(-))
      production induced by LPS. Furthermore, the effects of indomethacin were reverted
      by exogenous PGE(2) and forskolin, whereas AH23848B, an EP(4) PGE(2) subtype
      receptor antagonist, decreased NO(2)(-) release. On the other hand, the effect of
      baicalein on NO(-)(2) production was reverted by exogenous LTB(4) and the fibrate
      WY 14,643, a natural and a synthetic peroxisome proliferator-activated receptor
      alpha (PPAR alpha), respectively. Thus, PGE(2) via EP(4) receptor/cAMP and LTB(4)
      via PPAR alpha may be involved in the control of NO synthesis by LPS in
      macrophage RAW 264.7 cultures.

PMID- 12009844
TI  - The effect of oxidative stress on endothelium-dependent and nitric oxide donor
      induced relaxation: implications for nitrate tolerance.
AB  - Increased inactivation of nitric oxide (NO) by superoxide has been implicated in
      nitrate tolerance. Here, we set out to compare the inhibitory effect of
      superoxide on endothelium-dependent, acetylcholine (ACh)-mediated vascular
      relaxation with that on the endothelium-independent effects of glyceryl
      trinitrate (GTN) and another NO donor drug, S-nitrosoglutathione (GSNO). Rings of
      thoracic aorta from adult male Wistar rats (350-450 g) were precontracted with
      phenylephrine (approximately EC(90)) prior to cumulative additions (10 nM/L-10
      microM/L) of GTN, GSNO, or ACh. Rings were then treated with the superoxide
      generator pyrogallol (300 micromol/L) alone or following pretreatment with the
      Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate (DETCA; 100
      micromol/L), and cumulative additions of the vasodilators were repeated. All
      experiments were conducted in the presence of catalase (3000 U/ml) to prevent
      accumulation of hydrogen peroxide. Relaxation to ACh was abolished by pyrogallol
      derived superoxide. Relaxation to GSNO was significantly inhibited by superoxide
      (P < 0.05, n = 8) and was more pronounced at lower GSNO concentrations. However,
      GTN was relatively resistant to inhibition by superoxide with modest inhibition
      only occurring in rings pretreated with DETCA prior to pyrogallol (P < 0.05; n =
      8). In contrast to GSNO, the inhibitory effect was more pronounced with high
      concentrations of GTN, suggesting that the mechanism underlying superoxide
      mediated inhibition is different for the two NO donor drugs. Further experiments
      showed that vascular responses to ACh were not inhibited (P > 0.05, n = 6) in
      aortic rings made tolerant to GTN (10 micromol/L, 2-h incubation) and that
      treatment of vessels with the antioxidant vitamin C (1 mmol/L) successfully
      prevented the development of tolerance. Taken together, these results suggest
      that superoxide is not a major factor in tolerance in vitro and imply that the
      protective actions of vitamin C are unrelated to its antioxidant activity in this
      setting.

PMID- 12009845
TI  - Inhibition of inducible NO synthase by TH2 cytokines and TGF beta in rheumatoid
      arthritic synoviocytes: effects on nitrosothiol production.
AB  - The aim of this study was to compare the effects on NO production of IL-4, IL-10,
      and IL-13 with those of TGF-beta. RA synovial cells were stimulated for 24 h with
      IL-1 beta (1 ng/ml), TNF-alpha (500 pg/ml), IFN-gamma (10(-4)IU/ml) alone or in
      combination. Nitrite was determined by the Griess reaction, S-nitrosothiols by
      fluorescence, and inducible NO synthase (iNOS) by immunofluorescence and
      fluorescence activated cell sorter analysis (FACS). In other experiments, IL-4,
      IL-10, IL-13, and TGF beta were used at various concentrations and were added in
      combination with proinflammatory cytokines. The addition of IL-1 beta, TNF-alpha,
      and IFN-gamma together increased nitrite production: 257.5 +/- 35.8 % and S
      nitrosothiol production : 413 +/- 29%, P < 0.001. None of these cytokines added
      alone had any significant effect. iNOS synthesis increased with NO production. IL
      4, IL-10, IL-13, and TGF beta strongly decreased the NO production caused by the
      combination of IL-1 beta, TNF-alpha, and IFN-gamma. These results demonstrate
      that stimulated RA synoviocytes produce S-nitrosothiols, bioactive NO* compounds,
      in similar quantities to nitrite. IL-4, IL-10, IL-13, and TGF-beta decrease NO
      production by RA synovial cells. The anti-inflammatory properties of these
      cytokines may thus be due at least in part to their effect on NO metabolism.

PMID- 12009846
TI  - Antifibrotic role of inducible nitric oxide synthase.
AB  - Long-term treatment in rats with l-NAME, an isoform-non-specific inhibitor of
      nitric oxide synthase (NOS), leads to fibrosis of the heart and kidney,
      suggesting that nitric oxide (NO) may play a role in preventing tissue fibrosis.
      In this process, a likely target of NO is the quenching of reactive oxygen
      species (ROS) through peroxynitrite formation, and one possible source for this
      NO is inducible NOS (iNOS). Using Peyronie's disease (PD) tissue from both human
      specimens and from a rat model of PD as the source of fibrotic tissue, we
      investigated if NO derived from iNOS could act as such an antifibrogenic defense
      mechanism by determining whether: (a) tunical ROS and iNOS are increased in PD;
      and (b) the long-term inhibition of iNOS activity decreases the NO/ROS balance in
      the tunica albuginea thereby promoting collagen deposition. It was determined
      that in the human PD plaque, iNOS mRNA and protein, ROS, collagen, and the
      peroxynitrite marker, nitrotyrosine, were all increased in comparison to the
      normal tunica. In the rat model of PD, the fibrotic plaque also showed
      significant increases in iNOS mRNA and protein, nitrotyrosine, ROS as measured by
      heme oxygenase-1, and collagen when compared with the normal control tunica. When
      a selective inhibitor of iNOS, L-NIL, was given to rats with the PD-like plaque,
      this resulted in a decrease in nitrotyrosine levels but intensified ROS levels
      and collagen deposition. These data demonstrate that: (a) iNOS induction occurs
      in both the human and rat PD fibrotic plaque; and (b) that the NO derived from
      iNOS appears to counteract ROS formation and collagen deposition. Because the
      inhibition of iNOS activity leads to a decrease in the NO/ROS ratio, thereby
      favoring the development of fibrosis, it is proposed that iNOS induction in this
      tissue may be a protective mechanism against fibrosis and abnormal wound healing.

PMID- 12009847
TI  - Time course of NADH oxidase, inducible nitric oxide synthase and peroxynitrite in
      diabetic retinopathy in the BBZ/WOR rat.
AB  - This study investigated the time course of NADH oxidase, a source of superoxide
      in the vascular endothelium, inducible nitric oxide synthase (iNOS), and
      peroxynitrite (ONOO(-)) in the BBZ/Wor rat, a spontaneous model of noninsulin
      dependent diabetes (NIDDM). Colloidal gold-labeled immunocytochemical studies of
      iNOS and nitrotyrosine, a marker for OONO(-), were done on sections of retinas
      from male BBZ/Wor rats in which NADH oxidase was localized by cerium derived
      cytochemistry at three time points: pre-diabetes (prior to the onset of
      hyperglycemia); new onset diabetes (2-6 days after onset of hyperglycemia); and
      chronic diabetes (4-18 months after onset of hyperglycemia). Control retinas were
      from age matched non-diabetic BB(DR)/Wor rats. The percentage of blood vessels
      positive for NADH oxidase increased significantly (P = 0.05) in new onset (64.2
      +/- 6.5%) and chronic diabetes (83.2 +/- 11.4%), as compared to pre-diabetes
      (25.8 +/- 5.6%) and nondiabetic controls (33.6 +/- 15.9%). The percentage of
      blood vessels positive for iNOS immunoreactivity was significantly higher in new
      onset diabetic retinas (69.6 +/- 5.88%, P = 0.0001; 8.9 +/- 3.29 colloidal gold
      particles (cgp) /50 microm(2)) than in chronic diabetic retinas (49.9 +/- 9.75%;
      7.9 +/- 5.12 cgp) and both were significantly higher (P = 0.0001) than in
      prediabetic (3.7 +/- 0.81%; 0.4 +/- 0.56 cgp) and nondiabetic control retinas
      (8.7 +/- 4.66%; 1.2 +/- 1.40 cgp). In new onset diabetes, levels of nitrotyrosine
      immunoreactivity (60.8 +/- 16.91 cgp) were significantly higher (P = 0.0001) than
      those in chronic diabetes (29.5 +/- 4.31 cgp); both were significantly higher (P
      = 0.0001) than those in prediabetic (8.2 +/- 1.70 cgp) and nondiabetic retinas
      (9.0 +/- 1.87 cgp). There was no cumulative increase in nitrotyrosine in the
      chronic diabetic retinas as a function of time. In rats with diabetes there was
      disruption of the inner blood-retinal barrier. These results suggest that iNOS
      and ONOO(-) may contribute to retinal damage in diabetes from the onset of
      hyperglycemia in NIDDM.

PMID- 12009848
TI  - Selective delivery of nitric oxide to a cellular target: a pseudosubstrate
      coupled dinitrosyl-iron complex inhibits the enteroviral protease 2A.
AB  - Nitric oxide (NO) regulates multiple biological processes. To use NO as a
      potential therapeutic substance, a more selective modulation of individual NO
      targets is desirable. Here, we tested whether peptide conjugation of the
      dinitrosyl-iron complex (DNIC), a potent NO donor, confers targeted NO delivery.
      As target, we used the protease 2A of Coxsackie-B-viruses (2A(pro)), which can
      cause dilated cardiomyopathy. Through S-nitrosylation, NO inhibits this protease,
      which is essential for viral replication. The tetrapeptide Leu-Ser-Thr-Cys (LSTC)
      (based on the 2A(pro) substrate recognition motif) and DNIC generated LSTC-DNIC
      in vitro by S-nitrosylation as evidenced by reverse-phase chromatography. In
      vitro, LSTC-DNIC (IC(50) 510 nM) dose-dependently inhibited purified 2A(pro) 4.7
      fold more effectively than DNIC (IC(50) 2.4 microM), whereas LSTC alone had no
      effect. In intact cells, expression of Coxsackievirus protease 2A by transient
      transfection led to eIF4G-I-cleavage. LSTC-DNIC (IC(50) 23 microM) dose
      dependently inhibited eIF4G cleavage in 2A(pro)-transfected cells 3.8-fold more
      effectively than DNIC (IC(50) 88 microM). To test the specificity of the DNIC
      conjugated LSTC peptide part, we investigated its influence on Caspase-3, a known
      target for S-nitrosylation. LSTC-DNIC and DNIC inhibited purified Caspase-3 in
      vitro (IC(50) 3.7 microM) and in intact cells similarly. LSTC conjugation of DNIC
      enhances its fidelity for inhibition of 2A(pro) in vitro and intracellularly.
      Peptide-DNIC may be useful to selectively modulate cellular processes by NO,
      i.e., to enhance its antiviral properties.

PMID- 12009849
TI  - Nitric oxide-mediated depletion of Langerhans cells from the epidermis may be
      involved in UVA radiation-induced immunosuppression.
AB  - Ultraviolet A (UVA) irradiation of the dorsal skin of mice reduced the contact
      hypersensitivity (CHS) response and the density of epidermal Langerhans cells
      (LC). The roles of nitric oxide (NO) and reactive oxygen species (ROS) in these
      biological effects of UVA were investigated. Topical application of N(G)
      monomethyl-L-arginine acetate, an inhibitor of NO production, 2,2'-dipyridyl, an
      iron chelater, or 4-hydroxy-tempo, a superoxide dismutase mimicking agent,
      inhibited UVA-induced suppression of the CHS response. N(G)-monomethyl-L-arginine
      acetate but not the ROS inhibitors prevented UVA from reducing LC numbers in the
      epidermis. This suggests that NO but not ROS produced in response to UVA mediates
      a depletion of LC from the epidermis, probably by signaling these cells to
      migrate from the skin. This could be responsible for UVA-induced
      immunosuppression. UVA-induced ROS can also cause immunosuppression, but by a
      different mechanism. Agents that inhibit or modulate NO or ROS production may be
      useful for preventing damage caused by the UVA component of sunlight to the skin
      immune system.

PMID- 12009850
TI  - JunB/AP-1 and NF-kappa B-mediated induction of nitric oxide synthase by bovine
      type I collagen in serum-stimulated murine macrophages.
AB  - Type I collagen comprises the majority of the total body collagens. In
      particular, bovine type I collagen is utilized for medical purposes and used
      widely in a variety of cell culture models as a fibrous component of
      extracellular matrix. This study was designed to explore the effects of type I
      collagen on the expression of inducible nitric oxide synthase (iNOS) in serum
      stimulated Raw264.7 cells and to study the molecular mechanistic basis. Bovine,
      but not rat or murine, type I collagen increased NO production in serum
      stimulated cells, which resulted from the induction of iNOS, as monitored by
      Northern and Western blot analyses. Bovine type I collagen in combination with
      serum activated JunB and JunB/AP-1 transcription complex, as evidenced by
      supershift and immunodepletion of the retarded AP-1 band with anti-JunB antibody.
      AP-1 complex was immunodepleted in part by anti-c-Jun or anti-JunD antibody.
      Extracellular signal-regulated kinase1/2 (ERK1/2), p38 kinase, and c-Jun N
      terminal kinase (JNK) were all activated by bovine type I collagen in serum
      stimulated cells. PD98059, but not SB203580 or JNK1(-) transfection, inhibited
      both ERK1/2 phosphorylation and JunB/AP-1 activation. Either PD98059 or MKK1(-)
      transfection suppressed the iNOS induction. The induction of iNOS accompanied
      activation of NF-kappa B with degradation of I-kappa B alpha. AP-1 and/or NF
      kappa B decoy oligonucleotides and pyrrolidine dithiocarbamate suppressed the
      iNOS induction, which confirmed involvement of AP-1 and NF-kappa B as
      transcription factors. These results demonstrated that bovine type I collagen
      induces iNOS in serum-stimulated murine macrophages through JunB/AP-1 and NF
      kappa B activation and that activation of ERK1/2 plays an essential role in
      JunB/AP-1 activation.

PMID- 12009851
TI  - Sequential NO production by mitochondria and endoplasmic reticulum during induced
      apoptosis.
AB  - Early stages of rat thymocyte apoptosis measured as annexin-V positive events and
      induced by methylprednisolone (MPS), etoposide, and thapsigargin, showed a
      sequential increase in nitric oxide (NO) production by mitochondrial and
      endoplasmic reticulum membranes. Thapsigargin induced the highest NO production,
      a sevenfold increase as compared with untreated thymocytes, in mitochondrial and
      microsomal membranes. MPS and etoposide were equally effective in increasing NO
      production by mitochondrial membranes by a factor of 4-5, with only a slight
      increase in NO production by endoplasmic reticulum membranes. Western blot
      analysis of both types of membrane indicated that a nitric oxide synthase (NOS)
      isoenzyme is present in mitochondrial membranes and reacts with antibodies to i
      NOS (type II), while reactivity to antibodies to e-NOS (type III) was restricted
      to endoplasmic reticulum. The participation of endoplasmic reticulum during
      apoptosis was further determined by alterations in UDP-Glucosyltransferase (UDP
      GT) and NADPH cytochrome P450 reductase. Increased UDP-GT activity was observed
      after thapsigargin treatment, and no changes were found after treatment with
      etoposide or MPS. NADPH cytochrome P450 reductase activity markedly decreased
      during apoptosis, being stronger after thapsigargin treatment. The latest stage
      of the apoptotic process was measured by caspase activities. Caspase 3 activity
      was markedly increased by the three apoptosis inducers; caspase 6 was only
      activated by MPS and etoposide, while caspase 8 was not activated by any of these
      inducers. It is clear that mitochondria and endoplasmic reticulum are involved in
      thapsigargin induced thymocyte apoptosis. Meanwhile, other thymocyte apoptotic
      pathways, such as those induced by MPS or etoposide, seem to centrally involve
      mitochondria but not endoplasmic reticulum.

PMID- 12009852
TI  - Aging impairs nitric oxide-mediated relaxant responses of rabbit corporal smooth
      muscle.
AB  - Aging has been reported to cause impotence, the mechanism of which is unknown.
      Therefore, we investigated the effect of aging on electrical stimulation-induced
      neurogenic, carbachol-induced, endothelium-dependent, and sodium nitroprusside
      induced cGMP-dependent relaxant responses of rabbit corporal smooth muscle. Male
      New Zealand white rabbits were divided into young (4 months), intermediate (8
      months), and old (24 months) groups. Electrical stimulation-, carbachol-, sodium
      nitroprusside-, and papaverine-induced relaxant response in isolated corporal
      smooth muscle strips were determined using in vitro muscle technique. Although
      there was no significant difference in the relaxant response of corporal strips
      to papaverine among the groups, relaxant responses to carbachol and sodium
      nitroprusside were significantly lower in corporal strips of old group than both
      young and intermediate groups. However, in the old and intermediate groups,
      electrical field stimulation-induced neurogenic relaxation was significantly
      reduced compared with the young group. KCl-induced (124 mM) contractile responses
      were the same in all groups. Our data indicate that the presence of age-dependent
      differences in the NO/cGMP-mediated relaxant responses of corporal tissue in the
      male rabbits. This may contribute to the development of impotence.

PMID- 12009853
TI  - Alcohol scavenges nitric oxide in gastric lumen.
AB  - The biological activities of endogenously produced nitric oxide (NO; nitrogen
      monoxide) can be affected not only by NO itself but also by relatively stable NO
      derived substances or by-products of NO. It is well known that NO-derived
      nitrosation at the center of nitrogen, sulfur, and carbon (N-, S-, and C
      nitrosation) have a great biological significance, while that at oxygen center (O
      nitrosation) remains to be detected. During the course of a physiologic study on
      ethanol-induced gastric injury employing an ex vivo gastric chamber system of
      rats, we found that ethanol could be nitrosated by endogenously produced NO.
      Luminal nitrite and nitrate (NOx) levels in gastric lumen were decreased sharply
      about 70% during ethanol saline solution infusion to the chamber and then
      immediately returned to the basal levels by infusion of ethanol-free saline
      solution. On the other hand, NO levels in gastric mucosa were slightly increased
      during the infusion of ethanol saline solution, suggesting that ethanol never
      inhibits NO biosynthesis. These results demonstrate that ethanol perfused in
      gastric lumen can scavenge gastric tissue-derived NO and ethanol may react with
      NO-derived species (probably, N(2)O(3)) to form an ethylnitrite in oxygen
      containing luminal solution. Alkyl nitrites including ethylnitrite have been not
      only widely used as a nitrovasodilator but also shown to act as a nitrosating
      agent. Thus, in vivo O-nitrosation also has important biological meaning in the
      same manner as N-, S-, and C-nitrosation.

PMID- 12009854
TI  - Variability of the paraoxonase gene (PON1) in Euro- and Afro-Brazilians.
AB  - The human high-density lipoprotein-associated paraoxonase (EC 3.1.1.2; PON1)
      plays a role in the hydrolysis of organophosphorus compounds and against the
      oxidative damage of low-density lipoprotein. In the present study, variants of
      PON1 (55 and 192) were investigated by PCR-RFLP and PCR-SSCA in Euro- (N = 101)
      and Afro-Brazilians (N = 70). The PON1*55 and PON1*192 allele frequencies were
      significantly different in these ethnic groups (p < 0.05 and p < 0.001,
      respectively). The genotype frequencies for PON1*55 (LL, LM, and MM) in Euro- and
      Afro-Brazilians were 33, 56, and 11% and 47, 49, and 4%, respectively. The
      genotype frequencies for PON1*192 were significantly different in Euro- and Afro
      Brazilians (QQ, QR, RR: 48, 42, and 10% and 21, 52, and 27%, respectively; p <
      0.001). The haplotype frequency distributions were also significantly different
      in Euro- (LQ = 30.20%; LR = 30.69%; and MQ = 39.11%) and Afro-Brazilians (LQ =
      24.97%; LR = 46.46%; MQ = 22.18%; and MR = 6.39%; p < 0.001). Linkage
      disequilibrium (D) in relation to the maximum expected value was higher in Euro-
      (100%) than in Afro-Brazilians (58%). We suggest that the high linkage
      disequilibrium in Caucasians and Asians characterized by the absence or very low
      frequency of the MR haplotype is mainly due to genetic drift and possibly also to
      natural selection favoring the PON1*192Q allele or a variant in linkage
      disequilibrium with it. This seems to be the first study on the PON1 variability
      at the DNA level in South American samples and one of the few studies on
      individuals of mixed African origin.

PMID- 12009855
TI  - In vitro estrogen receptor binding of PCBs: measured activity and detection of
      hydroxylated metabolites in a recombinant yeast assay.
AB  - The estrogenic activities of 17beta-estradiol, biphenyl, chlorinated biphenyls,
      and Aroclor mixtures 1221, 1242, and 1248 were measured with a modified
      recombinant yeast estrogen assay (i.e., a Saccharomyces cerevisiae-based lac-Z
      (beta-galactosidase) reporter assay). Modifications of the assay included the use
      of glass vials instead of plastic microtiter plates and the addition of the
      medium and yeast before the test substrate. 14C-labeled compounds were used to
      follow improvements in the assay procedures. 14C-17beta-estradiol recovery from
      plastic microtiter plates and glass vials using the standard or the modified
      procedure was approximately 89%. However, 14C-4-CB (4-chlorobiphenyl) recovery
      was considerably less, ranging from 3% in plastic microtiter plates using the
      standard procedure to 26% in vials using the modified procedure. These results
      suggest that the toxicity of strongly hydrophobic chemicals may be
      underestimated. Using the modified yeast estrogen assay, full agonist activity
      was observed for 4-CB, 2,4,6-CB, and 2,5-CB while each of the Aroclor mixtures
      were only partial agonists. The equivalent EC50 values in ppm were in
      environmentally relevant concentrations for biphenyl (19 ppm), 4-CB (4.5 ppm),
      2,5-CB (21 ppm), 2,4,6-CB (0.8 ppm), Aroclor 1221 (2.9 ppm), Aroclor 1242 (0.65
      ppm), and Aroclor 1248 (2.3 ppm). Estrogen receptor binding for the individual
      PCB congeners was 25- to 650-fold less than the reported estrogen binding for the
      corresponding hydroxylated PCB metabolite. Gas chromatographic/mass spectrometric
      analysis of yeast extracts indicated that S. cerevisiae hydroxylated the
      individual PCB congeners in the ppb range. With the exception of biphenyl, the
      concentration of hydroxylated metabolites obtained from incubation of S.
      cerevisiae with PCB congeners was consistent with the concentration necessary to
      elicit a positive estrogen receptor-binding response. This work provides evidence
      that S. cerevisiae are capable of metabolic transformation of PCBs and that
      estrogen receptor binding of PCBs is mediated through the hydroxylated metabolite
      rather than through the direct interaction of the PCB congeners with the estrogen
      receptor.

PMID- 12009856
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin does not directly alter the phenotype of
      maturing B cells in a murine coculture system.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), acting through the aromatic
      hydrocarbon receptor (AhR), elicits numerous toxicological effects, including
      immunosuppression. Previous work from our laboratory has suggested that TCDD
      exposure in mice is associated with altered lymphopoietic development, in
      particular altered B-cell phenotype in the bone marrow. It remains to be
      determined which specific hematopoietic populations or subpopulations within the
      marrow cavity are directly targeted by TCDD. To examine the effects of TCDD on
      developing B cells in vitro, a stromal coculture model was used. Primary bone
      marrow cells from male, 6- to 7-week-old C57Bl/6 mice were cocultured separately
      on two AhR-containing stromal cell lines (M2-10B4 and S17) that support B-cell
      development in the presence of IL-7. The cocultures were treated with 0 to 10 nM
      TCDD. Shifts in phenotype were quantified by cell surface marker staining and
      flow cytometry. Four populations in the maturing B cell (very early pre-pro-B,
      pre-pro-B, pro-B, and pre-B) were defined for quantification. The results show
      that the only statistically significant effect of TCDD was within the pre-pro-B
      population in cultures with the S17 stromal cell line. The increase in number of
      cells with this phenotype was seen in cultures with both wild-type and AhR-/-
      primary bone marrow cells. These results suggest that the maturing B220+ B cell
      is not the direct target for TCDD-induced bone marrow B-cell alterations.

PMID- 12009857
TI  - Gadolinium chloride pretreatment prevents cadmium chloride-induced liver damage
      in both wild-type and MT-null mice.
AB  - The heavy metal cadmium (Cd) causes hepatotoxicity upon acute administration.
      Kupffer cells, the resident macrophages of the liver, have been suggested to play
      a role in Cd-induced hepatotoxicity. Gadolinium chloride (GdCl3) may prevent Cd
      induced hepatotoxicity by suppressing Kupffer cells. However, GdCl3 also induces
      the Cd-binding protein, metallothionein (MT). Therefore, this study was conducted
      to determine whether GdCl3 prevents Cd-induced hepatotoxicity via the induction
      of MT. Hepatic MT and Kupffer cell counts were analyzed 24 h after wild-type (WT)
      mice were administered saline or 10, 30, or 60 mg GdCl3/kg. GdCl3 induced MT in a
      dose-dependent manner without affecting nonprotein sulfhydryl content. All
      examined doses of GdCl3 were effective at eliminating Kupffer cells from the
      liver. To examine the hepatoprotective effects of GdCl3, WT and MT-null mice were
      pretreated with saline or 10, 30, or 60 mg GdCl3 24 h prior to a hepatotoxic dose
      of Cd (2.5 mg Cd/kg). Blood and livers were removed 16 h later and analyzed for
      hepatotoxicity as well as MT, Cd, and Kupffer cell content. Hepatotoxicity was
      alleviated in both WT and MT-null mice that were pretreated with 30 or 60 mg
      GdCl3/kg, indicating that MT induction is not required for the hepatoprotective
      effects of GdCl3. Hepatic Cd content was not decreased by GdCl3, demonstrating
      that GdCl3 does not negatively affect Cd distribution to the liver. Kupffer cells
      were depleted at all three doses of GdCl3, whereas hepatoprotection was only
      observed at doses of 30 and 60 mg GdCl3/kg. This does not rule out Kupffer cells
      in the mechanism of Cd-induced hepatotoxicity, but it does suggest that GdCl3
      exerts hepatoprotective effects on the liver aside from depleting Kupffer cells.
      In summary, these data substantially rule out MT induction and decrease the
      importance of Kupffer cells as mechanisms of GdCl3-induced protection from Cd
      induced hepatotoxicity.

PMID- 12009858
TI  - Anticoagulants prevent monocrotaline-induced hepatic parenchymal cell injury but
      not endothelial cell injury in the rat.
AB  - Monocrotaline (MCT) is a pyrrolizidine alkaloid plant toxin that produces
      hepatotoxicity in humans and animals. Human exposure to MCT occurs through
      consumption of contaminated grains and herbal medicines. Administration of MCT to
      rats stimulates activation of the coagulation system and fibrin deposition in the
      liver. Fibrin deposition occurs simultaneously with endothelial cell damage and
      prior to hepatic parenchymal cell injury. Accordingly, the hypothesis that
      activation of the coagulation system is required for MCT-induced liver injury was
      tested. Treatment of rats with either heparin or warfarin significantly reduced
      MCT-induced activation of the coagulation system and the increase in alanine
      aminotransferase activity in the plasma, a biomarker of hepatic parenchymal cell
      injury. Histopathological examination of liver sections revealed that heparin
      decreased parenchymal cell necrosis but did not affect central venular
      endothelial cell damage, congestion and dilation of the sinusoids, or hemorrhage
      in the liver. Morphometric analysis revealed that 28% of the area of livers from
      MCT-treated rats contained regions of coagulative necrosis, whereas less than 5%
      of the area of livers from rats treated with MCT and heparin contained these
      regions. By contrast, neither heparin nor warfarin prevented MCT-induced damage
      to endothelial cells in the liver as estimated by increased plasma hyaluronic
      acid concentration. These results suggest that activation of the coagulation
      system is required for MCT-induced parenchymal cell injury but not endothelial
      cell injury in the liver.

PMID- 12009859
TI  - The effects of mycotoxins, fumonisin B1 and aflatoxin B1, on primary swine
      alveolar macrophages.
AB  - Mycotoxins were fungal metabolites that were widely present in feed and food;
      some of them were known to associate with human and animal disease. In the
      present study, the effects of fumonisin B1 (FmB1) and aflatoxin B1 (AFB1) on
      swine alveolar macrophages (AM) were examined by exposing primary cultures of
      swine AM to various concentrations of mycotoxins. Incubation of AM with 5
      microg/ml of FmB1 for 72 h led to a reduction in the number of viable cells to
      65% of the control levels. In the presence of 1.5 microg/ml of AFB1, the
      viability of AM falls to less than 41% of controls after 24 h exposure. FmB1, but
      not AFB1, induced the apoptosis of swine AM with evidence of DNA laddering and
      nuclear fragmentation. However, both FmB1 and AFB1 exposure induced the
      expression of apoptosis-related heat shock protein 72 (HSP 72) in AM. Swine AM
      treated with 50 ng/ml of FmB1 and 100 ng/ml of AFB1 for 24 h led to a reduction
      in phagocytic ability to approximately 55 and 36% of the control levels,
      respectively. Incubation of AM with FmB1 (2 and 10 microg/ml) for 24 h
      dramatically decreased the mRNA levels of interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNF-alpha). However, AFB1 treatment did not affect the
      expression of IL-1beta and TNF-alpha mRNA. The results suggest that both FmB1 and
      AFB1 are immunotoxic to swine AM but that they exert their toxic effects via
      different biochemical mechanisms.

PMID- 12009860
TI  - Morphological alterations and elevations in tumor necrosis factor-alpha,
      interleukin (IL)-1alpha, and IL-6 in mixed glia cultures following exposure to
      trimethyltin: modulation by proinflammatory cytokine recombinant proteins and
      neutralizing antibodies.
AB  - Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal
      degeneration, astrogliosis, and microglia reactivity with an associated elevation
      in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory
      cytokines in the TMT-induced glia response, mixed cortical glia cultures were
      exposed to TMT and morphological and cytokine responses were examined.
      Morphological changes in the glia monolayer, enlarged, rounded cell bodies and
      retraction of the monolayer into distinct GFAP+ dense processes, displayed a dose
      (1, 5, and 10 microM TMT) and temporal response (6-48 h), accompanied by
      clustering of OX-42+ microglia. Tumor necrosis factor-alpha (TNF), interleukin
      (IL)-1alpha, and IL-6 mRNA levels were elevated by 3 and 6 h of TMT (10 microM)
      and proteins by 24 h. Recombinant proteins for IL-1alpha (100 pg/ml) and IL-6 (10
      ng/ml) exacerbated the morphological response to TMT while those for TNFalpha
      (150 pg/ml) did not. Neutralizing antibodies (1:100) to IL-1alpha and IL-6 showed
      a slight decrease in the severity of the morphological response to TMT while, at
      24 h, TNFalpha antibodies (1:100) and an antibody cocktail offered a significant
      level of protection. At 6 h, the neutralizing antibodies to TNFalpha or IL-1alpha
      did not elevate basal cytokine mRNA levels, however, IL-6 and the cocktail of
      antibodies significantly elevated IL-1alpha, IL-1beta, and IL-6 mRNA levels. The
      specific elevation in IL-1alpha and IL-6 mRNA levels induced by TMT remained
      evident only in cells coexposed to anti-TNFalpha. Similar responses in cytokine
      mRNA levels were seen in cocultures of hippocampal neurons and glia exposed to
      TMT. These data suggest a relationship between microglia activation,
      proinflammatory cytokine release, and glia morphological responses, the
      significance of which remains to be determined, as well as, the impact on
      neuronal degeneration.

PMID- 12009861
TI  - Increasing the DNA damage threshold in breast cancer cells.
AB  - The biochemical role of estrogens in the development of estrogen-dependent breast
      cancer remains to be elucidated, and the involvement of estrogens in tumor
      initiation remains controversial. Reports regarding estrogen-mediated DNA damage
      include the induction of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in vitro and in vivo,
      indicating a role for oxidative stress in tumor initiation and/or progression.
      However, DNA isolation, cellular DNA repair, and high antioxidant status have
      made the measurement of 8-oxo-dG in vivo and in cell culture somewhat
      challenging. In this regard, a potentiation in DNA damage can be achieved by
      depleting cellular stores of glutathione. We chose to deplete glutathione in the
      estrogen receptor (ER)-positive MCF-7 breast cancer cell line with a gamma
      glutamylcysteine transpeptidase enzyme inhibitor buthionine sulphoximine (BSO)
      for the purpose of studying estrogen-induced DNA damage. Treatment of GSH
      depleted MCF-7 cells with 10 microM 2-OH-E2 or 4-OH-E2 for 30 min resulted in a
      statistically significant increase in 8-oxo-dG/10(5) dG of 127 and 160%,
      respectively. A potentiation in catechol estrogen-induced DNA damage was observed
      with the addition of copper(II) chloride for both 2-OH-E2 and 4-OH-E2 by 165 and
      200%, respectively. In addition, 100 nM and 1.0 microM estradiol increased DNA
      damage in a dose-response-like fashion by 145 and 189%, respectively. The
      depletion of GSH by BSO may prove to be an advantageous technique for the study
      of DNA damage in cells otherwise resistant to oxidative stress and/or alkylating
      agents and has proven useful in the study of estrogen-induced oxidative DNA
      damage in a highly reproducible and sensitive manner.

PMID- 12009865
TI  - Conformational changes accompanying self-assembly of the hepatitis C virus core
      protein.
AB  - Although a number of recent studies have suggested that the function of the
      hepatitis C virus (HCV) core protein may be both to package the viral genome and
      to modulate host cellular processes, little is known of the structure of the core
      protein necessary to accomplish these functions. Using in vitro assembled
      particles that mimic essential features of native HCV nucleocapsids, we report
      the earliest structural information of the HCV core protein and its nucleocapsid.
      The core protein is proteinase-resistant when assembled into nucleocapsid-like
      particles or complexed with nucleic acid in vitro. In contrast, the highly basic
      amino terminus of the free core protein is sensitive to proteolytic digestion.
      The hydrophobic carboxyl-terminal region of the core protein stabilizes the
      structure of the free core protein but is not required to stabilize core protein
      assembled into nucleocapsid-like particles or complexed to nucleic acid.
      Significantly, the carboxyl-terminal region is sufficient, but not necessary, to
      fold the core protein into a stable structure. These data are consistent with a
      model of a partially flexible HCV core protein that undergoes extensive
      conformational changes upon binding to nucleic acid and assembling into
      nucleocapsid particles. In addition, the susceptibility of nucleocapsid particles
      to RNase digestion suggests that RNA-core interactions may stabilize HCV
      nucleocapsids.

PMID- 12009866
TI  - Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of
      p21-activated kinase and increased production of HIV.
AB  - The negative factor (Nef) is one of six accessory proteins from primate
      lentiviruses (HIV-1, HIV-2, and SIV). It leads to high levels of viremia and the
      progression to AIDS in monkeys and humans. In this study, we demonstrated that
      Nef from HIV-1 binds to the regulatory subunit (p85) of phosphatidylinositol-3
      kinase (PI3K). This interaction depended on the C-terminus of p85 and Nef.
      Moreover, PI3K was required to activate the Nef-associated p21-activated kinase
      (PAK). Finally, inhibition of PI3K blocked the activation of PAK and decreased
      the production of viral particles to levels observed with the Nef-deleted
      provirus. We conclude that Nef assembles a multiprotein signaling complex which
      is required for the optimal replication of HIV-1.

PMID- 12009867
TI  - Characterization of nontypeable rotavirus strains from the United States:
      identification of a new rotavirus reassortant (P2A[6],G12) and rare P3[9] strains
      related to bovine rotaviruses.
AB  - Among 1316 rotavirus specimens collected during strain surveillance in the United
      States from 1996 to 1999, most strains (95%) belonged to the common types (G1 to
      G4 and G9), while 5% were mixed infections of common serotypes, rare strains, or
      not completely typeable. In this report, 2 rare (P[9],G3) and 2 partially
      typeable (P[6],G?; P[9],G?) strains from that study were further characterized.
      The P[6] strain was virtually indistinguishable by hybridization analysis in 10
      of its 11 gene segments with recently isolated P2A[6],G9 strains (e.g., U.S.1205)
      from the United States, but had a distinct VP7 gene homologous (94.7% a.a. and
      90.2% nt) to the cognate gene from P1B[4],G12 reference strain L26. Thus, this
      serotype P2A[6],G12 strain represents a previously unrecognized reassortant.
      Three P3[9] strains were homologous (97.8-98.2% aa) in the VP8 region of VP4 to
      the P3[9],G3 feline-like reference strain AU-1, but had a high level of genome
      homology to Italian bovine-like, P3[9],G3 and P3[9],G6 rotavirus strains. Two of
      the U.S. P3[9] strains were confirmed to be type G3 (97.2-98.2% VP7 aa homology
      with reference G3 strain AU-1), while the other was most similar to Italian
      bovine-like strain PA151 (P3[9],G6), sharing 99.0% a.a. homology in VP7. Cross
      neutralization studies confirmed all serotype assignments and represented the
      first detection of these rotavirus serotypes in the United States. The NSP4 genes
      of all U.S. P3[9] strains and rotavirus PA151 were most closely related to the
      bovine and equine branch within the DS-1 lineage, consistent with an animal
      origin. These results demonstrate that rare strains with P and G serotypes
      distinct from those of experimental rotavirus vaccines circulate in the United
      States, making it important to understand whether current vaccine candidates
      protect against these strains.

PMID- 12009868
TI  - Comparison of vaccine strategies using recombinant env-gag-pol MVA with or
      without an oligomeric Env protein boost in the SHIV rhesus macaque model.
AB  - Rhesus macaques were immunized with a replication-deficient vaccinia virus (MVA)
      expressing human immunodeficiency virus type 1 89.6 envelope (env) and SIV gagpol
      (MVA/SHIV89.6) with or without a protein boost consisting of soluble 89.6 env
      (gp140). Immunization with MVA/SHIV89.6 alone elicited binding antibodies in all
      animals and neutralizing antibodies in 5 of 15 animals. Both types of antibodies
      were enhanced by protein boosting. In addition, CD8 cells exhibiting CM9 tetramer
      binding were detected in the subset of animals that were Mamu-A*01 positive.
      Animals were challenged intravenously with either SHIV-89.6 (Study 1) or the more
      pathogenic derivative SHIV-89.6P (Study 2). In Study 1, all control and
      vaccinated animals except one became infected. However, the levels of viremia
      were as follows: controls > rMVA alone > rMVA + protein. The differences were
      statistically significant between immunized and control groups but not between
      the two immunized groups. In Study 2, all animals became infected; however, the
      vaccinated group exhibited a 5-fold reduction in peak viremia and a 10-fold
      reduction in the postacute phase viremia in comparison to the controls. All of
      the controls required euthanasia by 10 months after challenge. A relationship
      between vaccine-induced antibody titers and reduction in virus burden was
      observed in both studies. Thus, immunization with MVA/SHIV89.6 alone or with a
      protein boost stimulated both arms of the immune system and resulted in
      significant control of viremia and delayed progression to disease after challenge
      with SHIV-89.6P.

PMID- 12009869
TI  - Human immunodeficiency virus nucleocapsid protein polymorphisms modulate the
      infectivity of RNA packaging mutants.
AB  - The nucleocapsid protein (NC) of retroviruses is involved in viral RNA packaging
      and initiation of reverse transcription. NC also mediates interactions between
      Gag and actin filaments. We found that residues at the amino terminus of NC are
      involved in efficient actin binding. When alanine residues were substituted for
      the arginine and lysine at positions 10 and 11 of NC in HIV(NL4-3), these
      mutations decreased actin binding but had only a modest effect on virus
      infectivity. A similarly mutated virus based on the HXB2 clone of HIV was not
      infectious. Mutational analysis of NL4-3 NC residues demonstrated that NC
      polymorphisms modulated the phenotype of NC mutations. Conservative amino acid
      differences between HXB2 and NL4-3 NCs were sufficient to explain the difference
      in infectivity of viruses carrying the R10A and K11A mutations.

PMID- 12009870
TI  - Differential dependence of the infectivity of HIV-1 group O isolates on the
      cellular protein cyclophilin A.
AB  - The cellular protein Cyclophilin A (Cyp A) is packaged into human
      immunodeficiency virus type 1 (HIV-1) particles through a specific interaction
      with the capsid domain of the Gag polyprotein. Inhibition of Cyp A incorporation
      by mutagenesis or cyclosporin treatment severely affects infectivity of all HIV-1
      M subtypes tested. In contrast, the closely related lentiviruses HIV-2 and simian
      immunodeficiency virus (SIV) do not package Cyp A and are not inhibited by
      cyclosporin. For the HIV-1 group O isolate MVP5180, it was found that Cyp A
      incorporation and Cyp A dependence of infectivity did not correlate. This virus
      incorporates Cyp A but is not sensitive to treatment with cyclosporin A. For a
      more detailed study concerning the relationship between Cyp A incorporation and
      Cyp A dependence, we have analyzed five group O isolates for their ability to
      incorporate Cyp A and their sensitivity to cyclosporin treatment. All group O
      viruses incorporated Cyp A in comparable amounts as the M-group HIV-1 strain NL4
      3. Furthermore, Cyp A incorporation was inhibited by cyclosporin in all cases.
      However, while isolate MVP 5180 was confirmed to replicate independent of Cyp A,
      three of the other four isolates were sensitive to cyclosporin treatment.
      Sequence analysis of the Cyp A binding regions revealed that the proline-rich
      motif, which is responsible for Cyp A incorporation, was conserved in all four
      isolates, while some sequence variations were detected in other positions close
      to this region. These results suggest that Cyp A dependence of replication is
      influenced by regions outside the Cyp-binding loop and may aid in determination
      of Cyp A function in HIV-1 replication.

PMID- 12009871
TI  - Respiratory syncytial virus with the fusion protein as its only viral
      glycoprotein is less dependent on cellular glycosaminoglycans for attachment than
      complete virus.
AB  - Cell surface glycosaminoglycans (GAGs) are responsible for the majority of
      respiratory syncytial virus (RSV) attachment to cultured cells leading to
      infection. The viral glycoprotein G binds to GAGs and was thought to be the viral
      attachment protein, but more recently virus lacking the G protein was shown to be
      infectious in cell culture. We have compared the GAG dependence of a recombinant,
      green fluorescent protein-expressing virus containing the F protein as its only
      viral glycoprotein (rgRSV-F) to isogenic complete virus containing all three
      viral glycoproteins (rgRSV-SGF). Attachment and infection by each virus was found
      to be largely dependent on cell surface heparan sulfate (HS) based on the finding
      that both activities were inhibited by preincubation of virus with soluble HS, by
      removal of HS from target cells by enzymatic treatment or mutation, or by
      pretreatment of the target cells with basic fibroblast growth factor (bFGF),
      which binds HS. These results, coupled with the previous finding that SH is not
      involved in virion binding (S. Techaarpornkul, N. Barretto, and M. Peeples, 2001,
      J. Virol. 75, 6825-6834), suggest that, in the context of the virion, both the G
      and F proteins bind to HS. Interestingly, both rgRSV-F and rgRSV-SGF retained
      significant binding activity and infectivity despite these treatments, suggesting
      an alternate productive attachment and infection pathway. This property of GAG
      independence was particularly apparent for rgRSV-F virions, which retained nearly
      half of its attachment and infection activities in most of these experiments.
      Comparison of the attachment and infection activities of rgRSV-SGF and rgRSV-F
      virions with a Chinese hamster ovary cell line and a derivative thereof that is
      defective in GAG synthesis indicated that approximately 50% of rgRSV-SGF
      attachment is due to G protein-GAG binding, 25% to F protein-GAG binding, and 25%
      to an independent pathway. This alternative pathway presumably is mediated by the
      sole remaining viral surface protein, F, although the formal possibility exists
      that some other virion-associated protein is involved.

PMID- 12009872
TI  - Inter-retroviral fusion mediated by human immunodeficiency virus or murine
      leukemia virus glycoproteins: independence of cellular membranes and membrane
      vesicles.
AB  - We have recently demonstrated for the first time that inter-retroviral membrane
      fusion, i.e., membrane fusion between individual retroviral particle populations
      with incorporated HIV-1 Env and cellular receptors, respectively, can occur
      (Sparacio et al. 2000, Virology 271: 248-252). We have extended these analyses
      here and confirmed that fusion between particles can occur in the extracellular
      medium independent of any cellular membranes and that luciferase transduction,
      mediated by the fused structures, is independent of significant potential
      contribution by contaminating membrane vesicles. We have additionally analyzed
      whether membrane fusion between HIV-like particles can be mediated by amphotropic
      murine leukemia virus (MuLV) glycoprotein and its respective cellular receptor,
      PiT-2. We demonstrate that PiT-2 can be incorporated into HIV-like particles and
      can fuse with MuLV-Env-carrying particles. This occurs only in the situation in
      which the incorporated MuLV-Env protein has been activated to fusion activity by
      HIV protease-mediated removal of the C-terminal R-peptide and is completely
      inhibited when the respective particles are generated in the presence of the HIV
      protease inhibitor, Saquinavir.

PMID- 12009873
TI  - The complete genome sequence of Perina nuda picorna-like virus, an insect
      infecting RNA virus with a genome organization similar to that of the mammalian
      picornaviruses.
AB  - Perina nuda picorna-like virus (PnPV) is an insect-infecting RNA virus with
      morphological and physicochemical characters similar to the Picornaviridae. In
      this article, we determine the complete genome sequence and analyze the gene
      organization of PnPV. The genome of PnPV consists of 9476 nucleotides (nts)
      excluding the poly(A) tail and contains a single large open reading frame (ORF)
      of 8958 nts (2986 codons) flanked by 473 and 45 nt noncoding regions on the 5'
      and 3' ends, respectively. Northern blotting did not detect the presence of any
      subgenomic RNA. The PnPV genome codes for four structural proteins (CP1-4), and
      determination of their N-terminal sequences by Edman degradation, showed that all
      four are located in the 5' region of the genome. The 3' part of the PnPV genome
      contains the consensus sequence motifs for picornavirus RNA helicase, cysteine
      protease, and RNA-dependent RNA polymerase (RdRp) in that order from the 5' to
      the 3' end. In all of these characters, the genome organization of PnPV resembles
      the mammalian picornaviruses and two other insect picorna-like viruses,
      infectious flacherie virus (IFV) of the silkworm and Sacbrood virus (SBV) of the
      honeybee. In a phylogenetic tree based on the eight conserved domains in the RdRp
      sequence, PnPV formed a separate cluster with IFV and SBV, which suggests that
      these three insect picorna-like viruses might constitute a novel group of insect
      infecting RNA viruses.

PMID- 12009875
TI  - Complementation of a defective human adenovirus by an otherwise incompatible
      ovine adenovirus recombinant carrying a functional E1A gene.
AB  - All known human adenoviruses are classified as mastadenoviruses, while the ovine
      adenovirus (OAdV) serotype 7 is the prototype of the atadenoviruses, a proposed
      new genus. OAdV replicates abortively in human cell types and has potential as a
      gene transfer vector. However, the function of OAdV nonstructural genes is poorly
      understood and it is unclear whether OAdV replication might be complemented by a
      replicating human AdV in coinfected cells. To investigate possible interactions
      three human cell lines were singly infected with OAdV or human AdV5 or doubly
      infected. The development of a cytopathic effect and genome replication was
      monitored over three passages in each cell type. No significant OAdV replication
      occurred in any of the cell types examined either in the presence or in the
      absence of replicating AdV5. No aberrant AdV5 genome products were detected in
      coinfected cells. In contrast, in coinfected cells an OAdV recombinant that
      expressed the AdV5 E1A gene was able to promote the replication of an AdV5 E1A
      deficient mutant, demonstrating trans-complementation between appropriate
      viruses. These findings have implications for the biosafety of OAdV vectors and
      their possible utility for enhancing gene delivery.

PMID- 12009874
TI  - Kinetic analysis of glycoprotein C of herpes simplex virus types 1 and 2 binding
      to heparin, heparan sulfate, and complement component C3b.
AB  - Glycoprotein C (gC) from herpes simplex virus (HSV) facilitates virus entry by
      attaching the virion to host cell-surface heparan sulfate (HS). Although gC from
      HSV-1 (gC1) and from HSV-2 (gC2) bind to heparin, gC2 is believed to play a less
      significant role than gC1 in attachment of virus to cells. This attachment step
      is followed by the binding of gD to one of several cellular receptors. gC also
      plays an important role in immune evasion by binding to the C3b fragment of the
      third component of the host complement system. Yet, although both gC1 and gC2
      protect HSV against complement-mediated neutralization, only gC on HSV-1-infected
      cells acts as a receptor for C3b. We used optical biosensor technology to
      quantitate the affinities (K(D)) and the stabilities (k(off)) between both
      serotypes of gC with heparin, HS, and C3b to address three questions concerning
      gC interactions. First, can differences in affinity or stability account for
      differences between the contributions of HSV-1 and HSV-2 gC in attachment? Our
      data show that the gC2-HS complex is highly unstable (k(off) = 0.2 s(-1))
      compared to the gC1-HS complex (k(off) = 0.003 s(-1)), suggesting why gC2 may not
      play an important role in attachment of virus to cells as does gC1. Second, does
      gC2 have a lower affinity for C3b than does gC1, thereby explaining the lack of
      C3b-receptor activity on HSV-2 infected cells? Surprisingly, gC2 had a 10-fold
      higher affinity for C3b compared to gC1, so this functional difference in
      serotypes cannot be accounted for by affinity. Third, do differences in gC-HS and
      gD-receptor affinities support a model of HSV entry in which the gC-HS
      interaction is of lower affinity than the gD-receptor interaction? Our biosensor
      results indicate that gC has a higher affinity for HS than gD does for cellular
      receptors HveA (HVEM) and HveC (nectin-1).

PMID- 12009876
TI  - Characterization of complex B cell epitopes on woodchuck hepatitis virus surface
      antigens by using plasmids encoding chimeric proteins and DNA immunization.
AB  - The conformational nature of the B cell epitopes on the hepadnavirus surface
      antigens makes its characterization difficult. Here, a new approach by DNA
      vaccination with plasmids expressing chimeric hepadnavirus surface antigens was
      explored to determine B cell epitopes on the surface antigens of woodchuck
      hepatitis virus (WHsAg). A series of chimeric genes consisting of complementary
      fragments of WHsAg and hepatitis B virus surface antigens (HBsAg) was
      constructed. These plasmids expressed the following: (i) middle chimeric surface
      antigens (MCSAgs), including pre-S2 region and small surface antigens; (ii) small
      chimeric surface antigens (CSAgs); (iii) a mutated WHsAg with two amino acid
      substitutions, the Leu 136 to Thr and Ala 140 to Asp, within the central
      immunogenic region. The mutated region from amino acid 135 to 143 within WHsAg
      mimics the second loop of the HBsAg a-determinant. MCSAgs and CSAgs were
      expressed in transiently transfected mammalian cells and were reactive to anti
      HBsAg and anti-WHsAg, as shown by indirect immunofluorescence staining and ELISA.
      Vaccination with plasmids encoding MCSAgs induced strong antibody responses to
      the pre-S2 region. Anti-pre-S2 antibodies were directed to a linear,
      immunodominant region within the amino-terminal region of the pre-S2 region and
      were able to precipitate serum WHsAg. Vaccinations with the plasmids expressing
      the CSAgs led to the conclusion that an extended region aa 116-169 of WHsAg,
      analogous to the HBsAg a-determinant, was sufficient for the induction of anti
      WHsAg antibodies. The mutated WHsAg with the second loop of the HBsAg a
      determinant efficiently induced anti-WHsAg antibodies, but also a low titer of
      anti-HBsAg. Thus, multiple B cell epitopes of a linear and conformational nature
      are present on WHsAg. We presented an efficient and broadly applicable strategy
      for analysis of complex immunogenic determinants of natural or mutated viral
      antigens.

PMID- 12009877
TI  - A single glycosylation site within the receptor-binding domain of the avian
      sarcoma/leukosis virus glycoprotein is critical for receptor binding.
AB  - Retroviral envelope proteins are heavily glycosylated. In some cases,
      glycosylation has been shown to be important for folding, protein stability,
      immune evasion, or receptor usage. The receptor-binding subunit (SU or gp85) of
      the envelope protein (EnvA) of the avian sarcoma/leukosis virus, subtype A (ASLV
      A), contains 11 potential N-linked glycosylation sites (NXS/T). To address the
      importance of N-linked glycosylation for the function of EnvA, we prepared a
      series of EnvA proteins lacking one or more of these carbohydrate addition sites.
      Using site-directed mutagenesis, we mutated the S or T in each NXS/T
      glycosylation sequon to A. We also prepared EnvAs bearing selected double and
      triple mutations. We examined each mutant EnvA for its ability to be expressed at
      the cell surface, proteolytically processed into gp85 and gp37, incorporated into
      MLV pseudotyped virions, and to support infection of cells expressing the ASLV-A
      receptor, Tva. Eight single mutations were well tolerated, and, in general, EnvA
      was able to tolerate double mutations of these glycosylation sites. Triple
      mutations were more variable in their effects. Of the three glycosylation sites
      important for EnvA function, two are important for folding (EnvA production and
      processing were severely impaired). For the third, although EnvA processing was
      impaired, significant amounts of processed EnvA were expressed at the cell
      surface and incorporated into virions. Nonetheless, this mutant EnvA,
      EnvADeltaNg10, was unable to support infection. Further examination of
      EnvADeltaNg10 revealed that it was unable to bind Tva and was severely impaired
      for binding to a monoclonal antibody which inhibits receptor binding. This work
      has therefore identified a single N-linked glycosylation site in the SU domain of
      EnvA that is critical for binding between EnvA and its receptor, Tva.

PMID- 12009878
TI  - Dugbe nairovirus S segment: correction of published sequence and comparison of
      five isolates.
AB  - The sequence of the S (small) RNA segment of the ArD 44313 isolate of Dugbe
      nairovirus (DUG) has been redetermined, and a number of apparent errors in the
      previously reported sequence (V. K. Ward, A. C. Marriott, A. A. El-Ghorr, and P.
      A. Nuttall, 1990, Virology 175, 518-524) were revealed. Our results indicate that
      the S RNA is 1716 nucleotides (nt) in length and contains one large open reading
      frame spanning 1449 nt. This can encode a 483 amino acid polypeptide, M(r) 53.9
      kDa, corresponding to the viral nucleocapsid protein N. The DUG N protein is thus
      similar in length to the N proteins of Hazara (HAZ) and Crimean-Congo
      haemorrhagic fever (CCHF) nairoviruses, which are 485 and 482 amino acids in
      length, respectively. S segment RNA sequences were also determined for DUG
      isolates IbAr 1792, IbH 11480, ArD 16095, and KT 281/75; only the KT 281/75
      sequence differed markedly from that of ArD 44313. Phylogenetic trees were
      constructed for these nairovirus S segment sequences.

PMID- 12009879
TI  - Apoptosis induced in an early step of African swine fever virus entry into vero
      cells does not require virus replication.
AB  - Permissive Vero cells develop apoptosis, as characterized by DNA fragmentation,
      caspases activation, cytosolic release of mitochondrial cytochrome c, and flow
      cytometric analysis of DNA content, upon infection with African swine fever virus
      (ASFV). To determine the step in virus replication that triggers apoptosis, we
      used UV-inactivated virus, inhibitors of protein and nucleic acid synthesis, and
      lysosomotropic drugs that block virus uncoating. ASFV-induced apoptosis was
      accompanied by caspase-3 activation, which was detected even in the presence of
      either cytosine arabinoside or cycloheximide, indicating that viral DNA
      replication and protein synthesis were not required to activate the apoptotic
      process. The activation of caspase-3 was released from chloroquine inhibition 2 h
      after virus absorption, while the infection with UV-inactivated ASFV did not
      induce the activation of the caspase cascade. We conclude that ASFV induces
      apoptosis in the infected cell by an intracellular pathway probably triggered
      during the process of virus uncoating.

PMID- 12009880
TI  - Sequence analysis of the genome of porcine lymphotropic herpesvirus 1 and gene
      expression during posttransplant lymphoproliferative disease of pigs.
AB  - The porcine lymphotropic herpesvirus 1 (PLHV-1), the first gammaherpesvirus of
      pigs, has been detected at a high prevalence in healthy pig populations. A
      porcine gammaherpesvirus has also been detected at high copy numbers in animals
      suffering from posttransplant lymphoproliferative disease (PTLD). While human
      PTLD is a EBV-associated complication following clinical transplantation, porcine
      PTLD is a disease recently described in pigs undergoing experimental allogeneic
      hematopoietic stem cell transplantation. Here we demonstrate that PLHV-1 and the
      virus present in porcine PTLD are indistinguishable, and present the
      characterization of 73 kbp of the genome of PLHV-1. We identified homologs of
      cellular genes, including a putative G protein-coupled receptor (GCR) as well as
      a viral homolog of the bcl-2 oncogene (v-bcl-2) and show significant
      transcription of these genes as well as of several other PLHV-1 genes in lymph
      nodes of a PTLD-affected pig. These data indicate that PLHV-1 is active during
      PTLD and may be involved in the etiology of this lymphoproliferative disease.

PMID- 12009881
TI  - X-ray absorption spectroscopic investigation of the resting ferrous and
      cosubstrate-bound active sites of phenylalanine hydroxylase.
AB  - Previous studies of ferrous wild-type phenylalanine hydroxylase,
      [Fe(2+)]PAH(T)[], have shown the active site to be a six-coordinate distorted
      octahedral site. After the substrate and cofactor bind to the enzyme
      ([Fe(2+)]PAH(R)[L-Phe,5-deaza-6-MPH(4)]), the active site converts to a five
      coordinate square pyramidal structure in which the identity of the missing ligand
      had not been previously determined. X-ray absorption spectroscopy (XAS) at the Fe
      K-edge further supports this coordination number change with the binding of both
      cosubstrates to the enzyme, and determines this to be due to the loss of a water
      ligand.

PMID- 12009882
TI  - Insights into the functioning of Bacillus subtilis HPr kinase/phosphatase:
      affinity for its protein substrates and role of cations and phosphate.
AB  - In Bacillus subtilis, carbon catabolite repression is mediated by the HPr
      kinase/phosphatase (HprK/P) which catalyzes both an ATP-dependent phosphorylation
      and a dephosphorylation on Ser-46 of either HPr (histidine-containing protein) or
      Crh (catabolite repression HPr). By using a surface plasmon resonance approach,
      it was shown here that the presence of magnesium is a prerequisite for the
      interaction of HprK/P with either HPr or Crh. HprK/P binds both protein
      substrates with a similar affinity (K(D) of about 40 nM), and addition of
      nucleotides increases by about 10-fold its affinity for each substrate. In
      addition, the specificity and the concentration of the cation required for the
      binding of protein substrates are different from that exhibited by the cation
      binding site involved in the nucleotide binding, suggesting the presence of two
      cation-binding sites on HprK/P. The effects of phosphate on enzymatic activities
      of HprK/P were also investigated. Phosphate was able to unmask the phosphatase
      activity, especially in the presence of ATP or both ATP and fructose 1,6
      bisphosphate whereas it was shown to inhibit the kinase activity of HprK/P. An
      apparent competition between phosphate and a fluorescent analogue of nucleotide
      led to the suggestion that phosphate mediates its effect by binding directly to
      the ATP-binding site of the enzyme.

PMID- 12009883
TI  - Optimizing an artificial metabolic pathway: engineering the cofactor specificity
      of Corynebacterium 2,5-diketo-D-gluconic acid reductase for use in vitamin C
      biosynthesis.
AB  - The strict cofactor specificity of many enzymes can potentially become a
      liability when these enzymes are to be employed in an artificial metabolic
      pathway. The preference for NADPH over NADH exhibited by the Corynebacterium 2,5
      diketo-D-gluconic acid (2,5-DKG) reductase may not be ideal for use in industrial
      scale vitamin C biosynthesis. We have previously reported making a number of site
      directed mutations at five sites located in the cofactor-binding pocket that
      interact with the 2'-phosphate group of NADPH. These mutations conferred greater
      activity with NADH upon the Corynebacterium 2,5-DKG reductase [Banta, S.,
      Swanson, B. A., Wu, S., Jarnagin, A., and Anderson, S. (2002) Protein Eng. 15,
      131-140; (1)]. The best of these mutations have now been combined to see if
      further improvements can be obtained. In addition, several chimeric mutants have
      been produced that contain the same residues as are found in other members of the
      aldo-keto reductase superfamily that are naturally able to use NADH as a
      cofactor. The most active mutants obtained in this work were also combined with a
      previously reported substrate-binding pocket double mutant, F22Y/A272G. Mutant
      activity was assayed using activity-stained native polyacrylamide gels. Superior
      mutants were purified and subjected to a simplified kinetic analysis. The
      simplified kinetic analysis was extended for the most active mutants in order to
      obtain the kinetic parameters in the full-ordered bi bi rate equation in the
      absence of products, with both NADH and NADPH as cofactors. The best mutant 2,5
      DKG reductase produced in this work was the F22Y/K232G/R238H/A272G quadruple
      mutant, which exhibits activity with NADH that is more than 2 orders of magnitude
      higher than that of the wild-type enzyme, and it retains a high level of activity
      with NADPH. This new 2,5-DKG reductase may be a valuable new catalyst for use in
      vitamin C biosynthesis.

PMID- 12009884
TI  - Crystal structure of a zinc-activated variant of human carbonic anhydrase I, CA I
      Michigan 1: evidence for a second zinc binding site involving arginine
      coordination.
AB  - The human genetic variant carbonic anhydrase I (CA I) Michigan 1 results from a
      single point mutation that changes His 67 to Arg in a critical region of the
      active site. This variant of the zinc metalloenzyme appears to be unique in that
      it possesses an esterase activity that is specifically enhanced by added free
      zinc ions. We have determined the three-dimensional structure of human CA I
      Michigan 1 by X-ray crystallography to a resolution of 2.6 A. In the absence of
      added zinc ions, the mutated residue, Arg 67, points out of the active site,
      hydrogen bonding with the carboxylate of Asn 69. This contrasts with the
      orientation of His 67, in the native isozyme, which points into the active site.
      The orientations of His 94, His 96, and His 119, that coordinate the catalytic
      zinc ion, and of the catalytically critical Thr 199-Glu 106 hydrogen bonding
      system, are largely unchanged in the mutant. The structure of an enzyme adduct
      with a second zinc bound was determined to a resolution of 2.0 A. The second zinc
      ion is coordinated to His 64, His 200, and Arg 67. This arginine residue reverses
      its orientation on zinc binding and turns into the active site. The residues at
      these three positions have been implicated in determining the specific kinetic
      properties of native CA I. This is, to our knowledge, the first example of a zinc
      ion coordinating with an arginine residue in a Zn(II) enzyme.

PMID- 12009885
TI  - Relationship between protein structure and methionine oxidation in recombinant
      human alpha 1-antitrypsin.
AB  - alpha 1-Antitrypsin is a metastable and conformationally flexible protein that
      belongs to the serpin family of protease inhibitors. Although it is known that
      methionine oxidation in the protein's active site results in a loss of biological
      activity, there is little specific knowledge regarding the reactivity of each of
      the protein's methionine residues. In this study, we have used peptide mapping to
      study the oxidation kinetics of each of alpha 1-antitrypsin's methionines in
      alpha 1-AT((C232S)) as well as M351L and M358V mutants. These kinetic studies
      establish that Met1, Met226, Met242, Met351, and Met358 are reactive with
      hydrogen peroxide at neutral pH and that each reactive methionine is oxidized in
      a bimolecular, rather than coupled, mechanism. Analysis of Met226, Met351, and
      Met358 oxidation provides insights regarding the structure of alpha 1
      antitrypsin's active site that allow us to relate conformation to experimentally
      observed reactivity. The relationship between solution pH and methionine
      oxidation was also examined to evaluate methionine reactivity under conditions
      that perturb the native structure. Methionine oxidation data show that at pH 5,
      global conformational changes occur that alter the oxidation susceptibility of
      each of alpha 1-antitrypsin's 10 methionine residues. Between pH 6 and 9,
      however, more localized conformational changes occur that affect primarily the
      reactivity of Met242. In sum, this work provides a detailed analysis of
      methionine oxidation in alpha 1-antitrypsin and offers new insights into the
      protein's solution structure.

PMID- 12009886
TI  - The first strain of Clostridium perfringens isolated from an avian source has an
      alpha-toxin with divergent structural and kinetic properties.
AB  - Clostridium perfringens alpha-toxin is a 370-residue, zinc-dependent,
      phospholipase C that is the key virulence determinant in gas gangrene. It is also
      implicated in the pathogenesis of sudden death syndrome in young animals and
      necrotic enteritis in chickens. Previously characterized alpha-toxins from
      different strains of C. perfringens are almost identical in sequence and
      biochemical properties. We describe the cloning, nucleotide sequencing,
      expression, characterization, and crystal structure of alpha-toxin from an avian
      strain, SWan C. perfringens (SWCP), which has a large degree of sequence
      variation and altered substrate specificity compared to these strains. The
      structure of alpha-toxin from strain CER89L43 has been previously reported in
      open (active site accessible to substrate) and closed (active site obscured by
      loop movements) conformations. The SWCP structure is in an open-form
      conformation, with three zinc ions in the active site. This is the first example
      of an open form of alpha-toxin crystallizing without the addition of divalent
      cations to the crystallization buffer, indicating that the protein can retain
      three zinc ions bound in the active site. The topology of the calcium binding
      site formed by residues 269, 271, 336, and 337, which is essential for membrane
      binding, is significantly altered in comparison with both the open and closed
      alpha-toxin structures. We are able to relate these structural changes to the
      different substrate specificity and membrane binding properties of this divergent
      alpha-toxin. This will provide essential information when developing an effective
      vaccine that will protect against C. perfringens infection in a wide range of
      domestic livestock.

PMID- 12009887
TI  - Sequence-specific recognition of the major groove of RNA by deoxystreptamine.
AB  - Aminoglycoside antibiotics specifically interact with a variety of RNA sequences,
      and in particular with the decoding region of 16S ribosomal RNA in the aminoacyl
      tRNA acceptor site (A-site). Ring II of aminoglycosides (2-deoxystreptamine) is
      the most conserved element among aminoglycoside antibiotics that bind to the A
      site. NMR structures of aminoglycoside-A-site RNA complexes suggested that the 2
      deoxystreptamine core of aminoglycosides specifically recognizes (5')G-U(3') and
      potentially (5')G-G(3') or (5')U-G(3') steps in the major groove of RNA. Here, we
      show that isolated deoxystreptamine specifically interacts with G-U steps within
      the major groove of the A-site RNA. The bulge residue of A-site RNA is required
      to open the major groove for accommodation of deoxystreptamine. The chemical
      groups of deoxystreptamine presented to the RNA by the framework of the 6-carbon
      ring modulate RNA recognition.

PMID- 12009888
TI  - Domain flexibility in ligand-free and inhibitor-bound Escherichia coli adenylate
      kinase based on a mode-coupling analysis of 15N spin relaxation.
AB  - Adenylate kinase from Escherichia coli (AKeco), consisting of a 23.6-kDa
      polypeptide chain folded into domains CORE, AMPbd, and LID catalyzes the reaction
      AMP + ATP <--> 2ADP. The domains AMPbd and LID execute large-amplitude movements
      during catalysis. Backbone dynamics of ligand-free and AP(5)A-inhibitor-bound
      AKeco is studied with slowly relaxing local structure (SRLS) (15)N relaxation, an
      approach particularly suited when the global (tau(m)) and the local (tau) motions
      are likely to be coupled. For AKeco tau(m) = 15.1 ns, whereas for AKeco*AP(5)A
      tau(m) = 11.6 ns. The CORE domain of AKeco features an average squared order
      parameter, <S(2)>, of 0.84 and correlation times tau(f) = 5-130 ps. Most of the
      AKeco*AP(5)A backbone features <S(2)> = 0.90 and tau(f) = 33-193 ps. These data
      are indicative of relative rigidity. Domains AMPbd and LID of AKeco, and loops
      beta(1)/alpha(1), alpha(2)/alpha(3), alpha(4)/beta(3), alpha(5)/beta(4), and
      beta(8)/alpha(7) of AKeco*AP(5)A, feature a novel type of protein flexibility
      consisting of nanosecond peptide plane reorientation about the C(i-1)(alpha)
      C(i)(alpha) axis, with correlation time tau(perpendicular) = 5.6-11.3 ns. The
      other microdynamic parameters underlying this dynamic model include S(2) = 0.13
      0.5, tau(parallel) on the ps time scale, and a diffusion tilt beta(MD) ranging
      from 12 to 21 degrees. For the ligand-free enzyme the tau(perpendicular) mode was
      shown to represent segmental domain motion, accompanied by conformational
      exchange contributions R(ex) < or = 4.4 s(-1). Loop alpha(4)/beta(3) and
      alpha(5)/beta(4) dynamics in AKeco*AP(5)A is related to the "energetic counter
      balancing of substrate binding" effect apparently driving kinase catalysis. The
      other flexible AKeco*AP(5)A loops may relate to domain motion toward product
      release.

PMID- 12009889
TI  - Membrane orientation and position of the C2 domain from cPLA2 by site-directed
      spin labeling.
AB  - The C2 domain is a ubiquitous Ca(2+)-binding motif that triggers the membrane
      docking of many key signaling proteins during intracellular Ca(2+) signals. Site
      directed spin labeling was carried out on the C2 domain of cytosolic
      phospholipase A(2) in order to determine the depth of penetration and orientation
      of the domain at the membrane interface. Membrane depth parameters, Phi, were
      obtained by EPR spectroscopy for a series of selectively spin-labeled C2 domain
      cysteine mutants, and for spin-labeled lipids and spin-labeled bacteriorhodopsin
      cysteine mutants. Values of Phi were combined with several other constraints,
      including the solution NMR structure, to generate a model for the position of the
      C2 domain at the membrane interface. This modeling yielded an empirical
      expression for Phi, which for the first time defines its behavior from the bulk
      aqueous phase to the center of the lipid bilayer. In this model, the backbones of
      both the first and third Ca(2+)-binding loops are inserted approximately 10 A
      into the bilayer, with residues inserted as deep as 15 A. The backbone of the
      second Ca(2+)-binding loop is positioned near the lipid phosphate, and the two
      beta-sheets of the C2 domain are oriented so that the individual strands make
      angles of 30-45 degrees with respect to the bilayer surface. Upon membrane
      docking, spin labels in the Ca(2+)-binding loops exhibit decreases in local
      motion, suggesting either changes in tertiary contacts due to protein
      conformational changes and/or interactions with lipid.

PMID- 12009890
TI  - Structural consequences of tumor-derived mutations in p16INK4a probed by limited
      proteolysis.
AB  - The cyclin-dependent kinase inhibitor p16(INK4a) (hereafter p16) functions as a
      multiple tumor suppressor. Mutations in p16, which are distributed throughout the
      entire protein, have been identified in a variety of human cancers and cancer
      derived cell lines. It is unclear how tumor-derived mutations disrupt the
      structure and function of p16, especially since many of these mutations are
      located far away from the cyclin-dependent kinase binding site. In this study, we
      investigated the effect of two tumor-derived mutations, P81L and V126D, on the
      structure of p16 by limited proteolysis. The proteolytic products were
      characterized by gel electrophoresis, HPLC, and mass spectrometry. Our results
      show that the N-terminal half of p16 is significantly more sensitive to
      proteolysis in both tumor-derived mutant proteins than in the wild type,
      suggesting that this region is particularly unstable. Interestingly, the N
      terminal half of p16 contains many residues that are important for cyclin
      dependent kinase binding. Thus, our results provide a structural mechanism by
      which tumor-derived mutations inactivate the function of p16 and suggest that
      stabilization of the N-terminal region could be a useful strategy for future
      therapeutic development.

PMID- 12009891
TI  - Crystal structure of the core domain of RhoE/Rnd3: a constitutively activated
      small G protein.
AB  - We report the 2.1 A crystal structure of the core G protein domain of the unusual
      Rho family member RhoE/Rnd3 in complex with endogenous GTP and magnesium. Unlike
      other small G proteins, RhoE, along with two other proteins Rnd1/Rho6 and
      Rnd2/RhoN, does not hydrolyze GTP. The main reason for this is the presence of
      serines in the positions equivalent to Ala59 and Gln61 in Ras. The structure
      shows that there are still water molecules in similar positions to the waters
      thought to be involved in the hydrolysis reaction in other G proteins. The
      structure suggests three not necessarily exclusive explanations for the lack of
      hydrolysis. The lack of the conserved glutamine raises the energy of the
      transition state inhibiting hydrolysis. The serines may restrain the waters from
      moving closer to the GTP, a step that is required to attain the transition state.
      They also stabilize the GTP-bound conformation of switch II and could prevent
      conformational changes required during hydrolysis. By superposition of the RhoE
      structure on structures of Rho family proteins in complex with binding partners,
      we make predictions on RhoE interactions with these partners.

PMID- 12009893
TI  - Focal adhesion protein FAP52 self-associates through a sequence conserved among
      the members of the PCH family proteins.
AB  - FAP52 is a recently described focal adhesion-associated protein. It is a member
      of an emerging PCH (pombe Cdc15 homology) family of proteins characterized by a
      common domain organization and involvement in actin cytoskeleton organization,
      cytokinesis, and vesicular trafficking. Using gel filtration, surface plasmon
      resonance, and native polyacrylamide gel electrophoresis analysis, combined with
      chemical cross-linking of both native and recombinant protein, we show that FAP52
      self-associates in vitro and suggest that it occurs predominantly as a trimer
      also in vivo. Analysis of the various domains of FAP52 by surface plasmon
      resonance showed that the highly alpha-helical region in the N-terminal half of
      the protein provides the self-association interface. Overexpression of the
      oligomerization domain in cultured cells was accompanied by major alterations in
      cellular morphology, actin organization, and the structure of focal adhesions,
      suggesting that an orderly coming together of FAP52 molecules is crucial for a
      proper actin filament organization and cytoskeletal structure. Comparison of the
      primary structures shows that all of the members of the PCH family have, in their
      N-terminal halves, a similar, highly alpha-helical region, suggesting that they
      all have a capacity to self-associate.

PMID- 12009892
TI  - Lecithin retinol acyltransferase forms functional homodimers.
AB  - Membrane-bound lecithin retinol acyltransferase (LRAT), an essential enzyme in
      vitamin A processing, catalyzes the formation of retinyl esters from vitamin A
      and lecithin. Cloned and expressed LRAT has a molecular mass of 25.3 kDa. The
      enzyme is not homologous to known enzymes and is, therefore, of substantial
      interest mechanistically. Along these lines, the functional protomeric state of
      LRAT is of importance. Gel electrophoretic studies on LRAT in the presence of SDS
      and disulfide reducing agents show the expected 25 kDa monomer. However, gel
      electrophoresis in the absence of a reducing agent and/or strong denaturing
      conditions reveals substantial dimer formation. LRAT monomers can be efficiently
      and irreversibly cross-linked by thiol reactive bismaleimides in retinal pigment
      epithelial (RPE) membranes generating LRAT homodimers. Cross-linked LRAT
      homodimers are fully active catalytically. The experiments suggest that LRAT
      monomers interact in membranes and form functional homodimers through protein
      protein interactions and disulfide bond formation.

PMID- 12009894
TI  - Structure-based mutational and functional analysis identify human NM23-H2 as a
      multifunctional enzyme.
AB  - The human NM23-H2 protein is a transcriptional regulator (PuF) that binds and
      cleaves DNA via covalent bond formation, and also catalyzes phosphoryl transfer
      (NDP kinase). Our previous work has identified two separate DNA-binding regions
      on NM23-H2/PuF: a sequence-dependent DNA-binding surface involving residues
      Arg34, Asn69, and Lys134 on the equator of the hexameric protein and a covalent
      DNA-binding site involving Lys12 located in the nucleotide-binding site, the site
      of the NDP kinase reaction. To understand the role of the nucleotide-binding site
      in the DNA cleavage reaction and to establish a connection between the nuclease
      and the NDP kinase activities, we used the known crystal structure of NM23-H2
      complexed with GDP as the basis for site-directed mutagenesis. We thus identified
      Arg88 and Arg105 as residues that are, in addition to Lys12, critical for
      covalent DNA binding and DNA cleavage, as well as for the NDP kinase reaction.
      Another residue, Gln17, was required only for DNA cleavage, and Tyr52, Asn115,
      and His118 were found to be essential only for the NDP kinase activity. Six of
      these seven functionally important amino acids associated with the nucleotide
      binding site are evolutionarily conserved, underscoring their biological
      importance. We also show that nucleoside triphosphates but not nucleoside
      diphosphates inhibited the covalent DNA binding and DNA cleavage reactions,
      independent of phosphoryl transfer and the NDP kinase reaction. These findings
      collectively suggest that the binding modes of mononucleotides and duplex DNA
      oligonucleotides in the nucleotide-binding site differ, and that NM23-H2
      possesses multiple biochemical activities. A model consistent with these
      observations is presented.

PMID- 12009895
TI  - Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and
      interacts with the epidermal growth factor receptor.
AB  - We have identified physical and functional interactions between the epidermal
      growth factor (EGF) receptor and phospholipid scramblase 1 (PLSCR1), an
      endofacial plasma membrane protein proposed to affect phospholipid organization.
      PLSCR1, a palmitoylated protein, was found to partition with the EGF receptor in
      membrane lipid rafts. Cell stimulation with EGF transiently elevated Tyr
      phosphorylation of PLSCR1, peaking at 5 min. Although PLSCR1 is a known substrate
      of c-Abl [Sun, J., et al. (2001) J.Biol. Chem. 276, 28984-28990], the Abl
      inhibitor STI571 did not substantially affect its EGF-dependent phosphorylation,
      suggesting PLSCR1 is a substrate of the EGF receptor kinase, or another EGF
      activated kinase. Coinciding with phosphorylation, there was a transient increase
      in physical association of PLSCR1 with both the EGF receptor and the adapter
      protein Shc, as determined by immunoprecipitation and Western blotting. Confocal
      immunofluorescence analysis revealed that EGF initiates rapid internalization of
      both the EGF receptor and PLSCR1, with trafficking into both distinct and common
      endosomal pools. These data also suggested that whereas the EGF receptor is
      ultimately degraded, much of the endocytosed PLSCR1 is recycled to the cell
      surface within 3 h after EGF treatment. Consistent with this interpretation,
      Western blotting revealed neither ubiquitination nor proteolysis of PLSCR1 under
      these conditions, whereas the ubiquitination and degradation of the EGF receptor
      were readily confirmed. Finally, stimulation with EGF was also found to markedly
      increase the total cellular expression of PLSCR1, suggesting that in addition to
      its initial interactions with activated EGF receptor, PLSCR1 may also contribute
      to posttranscriptional effector pathway(s) mediating the cellular response to
      EGF.

PMID- 12009896
TI  - Identification of human vesicle monoamine transporter (VMAT2) lumenal cysteines
      that form an intramolecular disulfide bond.
AB  - The vesicle monoamine transporter (VMAT2) concentrates monoamine neurotransmitter
      into synaptic vesicles. To obtain structural information regarding this large
      membrane protein by analysis of disulfide bonds and other intramolecular cross
      links, we engineered a strategic thrombin cleavage site into deglycosylated, HA
      tagged human VMAT2. Insertion of this protease site did not disrupt ligand
      binding or serotonin transport. Thrombin cleavage at an engineered site in the
      predicted cytoplasmic loop between transmembrane (TM) domains 6 and 7 (loop 6/7)
      was rapid and quantitative in the absence of any detergent. The loop 6/7 thrombin
      site allowed assessment of an intramolecular disulfide bond between the N- and C
      terminal halves of the transporter. Consistent with this hypothesis, after
      quantitative loop 6/7 thrombin cleavage, in the absence of reducing agent, VMAT2
      migrated on SDS-polyacrylamide gels as a full-length transporter. Addition of
      dithiothreitol resulted in complete conversion from full-length to thrombin
      cleaved size, demonstrating a DTT-reversible covalent bond. The identity of the
      disulfide-bound cysteine pair was suggested by the observation that replacement
      of Cys 126 or Cys 333 with serine both reduced [(3)H]serotonin transport.
      Replacement of either Cys 126 or Cys 333 was found to eliminate the DTT
      reversible intramolecular covalent bond. We conclude that human VMAT2 Cys 126 in
      loop 1/2 and Cys 333 in loop 7/8 form a disulfide bond which contributes to
      efficient monoamine transport.

PMID- 12009897
TI  - Conformational energetics of rhodopsin modulated by nonlamellar-forming lipids.
AB  - Rhodopsin is an important example of a G protein-coupled receptor (GPCR) in which
      11-cis-retinal is the ligand and acts as an inverse agonist. Photolysis of
      rhodopsin leads to formation of the activated meta II state from its precursor
      meta I. Various mechanisms have been proposed to explain how the membrane
      composition affects the meta I-meta II conformational equilibrium in the visual
      process. For rod disk membranes and recombinant membranes containing rhodopsin,
      the lipid properties have been discussed in terms of elastic deformation of the
      bilayer. Here we have investigated the relation of nonlamellar-forming lipids,
      such as dioleoylphosphatidylethanolamine (DOPE), together with
      dioleoylphosphatidylcholine (DOPC), to the photochemistry of membrane-bound
      rhodopsin. We conducted flash photolysis experiments for bovine rhodopsin
      recombined with DOPE/DOPC mixtures (0:100 to 75:25) as a function of pH to
      explore the dependence of the photochemical activity on the monolayer curvature
      free energy of the membrane. It is well-known that DOPC forms bilayers, whereas
      DOPE has a propensity to adopt the nonlamellar, reverse hexagonal (H(II)) phase.
      In the case of neutral DOPE/DOPC recombinants, calculations of the membrane
      surface pH confirmed that an increase in DOPE favored the meta II state.
      Moreover, doubling the PE headgroup content versus the native rod membranes
      substituted for the polyunsaturated, docosahexaenoic acyl chains (22:6 omega 3),
      suggesting rhodopsin function is associated with a balance of forces within the
      bilayer. The data are interpreted by applying a flexible surface model, in which
      the meta II state is stabilized by lipids tending to form the H(II) phase, with a
      negative spontaneous curvature. A simple theory, based on principles of surface
      chemistry, for coupling the energetics of membrane proteins to material
      properties of the bilayer lipids is described. For rhodopsin, the free energy
      balance of the receptor and the lipids is altered by photoisomerization of
      retinal and involves curvature stress/strain of the membrane (frustration). A new
      biophysical principle is introduced: matching of the spontaneous curvature of the
      lipid bilayer to the mean curvature of the lipid/water interface adjacent to the
      protein, which balances the lipid/protein solvation energy. In this manner, the
      thermodynamic driving force for the meta I-meta II conformational change of
      rhodopsin is tightly controlled by mixtures of nonlamellar-forming lipids having
      distinctive material properties.

PMID- 12009898
TI  - Cellular cholesterol stimulates acute uptake of palmitate by redistribution of
      fatty acid translocase in type II pneumocytes.
AB  - Cholesterol is an abundant lipid of lung surfactant, where its concentration
      changes relative to phospholipids in response to certain physiological
      conditions. We investigated the effect of the cellular cholesterol content on
      uptake and esterification of palmitic acid, and on cellular distribution of fatty
      acid translocase (FAT/CD36) in alveolar type II cells. Incubation of type II
      cells with methyl-beta-cyclodextrin-cholesterol complexes increased the
      cholesterol content of lamellar bodies. The palmitate uptake of type II cells
      increased in parallel with the cellular cholesterol content. The content of
      FAT/CD36 increased in membranes and decreased in cytosol in type II cells. The
      detergent-insoluble fraction (DIGs), isolated from type II cells, was enriched in
      FAT/CD36 and caveolin-1 after increasing the cellular cholesterol. The total
      incorporation of labeled palmitic acid into glycerolipids and cholesterol ester
      (CE) increased by a factor of about 10 when the amount of unbound (14)C-palmitic
      acid added to type II cells was increased by a factor of about 1000. Under these
      conditions, a small but significant increase of the palmitate incorporation into
      PL occurred. Independent from the amount of added palmitate, palmitate
      incorporation into triacylglycerol decreased and palmitate incorporation into
      cholesterol ester increased about 40-65-fold. The beta-oxidation of palmitate
      significantly decreased. We conclude that alveolar type II cells respond to an
      increase of the cholesterol level with (i) cellular redistribution of FAT/CD36
      into DIGs causing enhanced palmitate uptake and increased cholesterol ester
      formation, (ii) storage of cholesterol in lamellar bodies, and (iii) induction of
      the formation of caveolae-like microdomains in the surface membrane, a structure
      possibly involved in a lamellar body-independent efflux of free cholesterol via
      the high-density lipoprotein-specific pathway.

PMID- 12009899
TI  - A modeled hydrophobic domain on the TCL1 oncoprotein mediates association with
      AKT at the cytoplasmic membrane.
AB  - AKT has a critical role in relaying cell survival and proliferation signals
      initiated by ligand binding to surface receptors in mammalian cells. Induction of
      AKT serine/threonine kinase activity is augmented by the T-cell leukemia-1 (TCL1)
      oncoprotein through a physical association requiring the AKT pleckstrin homology
      domain. Here, we used molecular modeling and identified an exposed hydrophobic
      patch composed of two discontinuous amino acid stretches near one end of the TCL1
      beta-barrel that was required for a TCL1-AKT association. Site-directed mutations
      of this region did not affect TCL1 secondary structure, yet they disrupted
      interactions with AKT. This region was found in other members of the TCL1
      oncoprotein family, such as TCL1b and MTCP1, and suggested a conserved, novel AKT
      binding domain. Interestingly, TCL1 and AKT co-localize in multiple cell
      compartments, but only extracts from the plasma membrane stimulate optimal
      complex formation in vitro. Identification of an AKT binding domain on TCL1 is an
      important step in deciphering the complex interactions that regulate AKT kinase
      activity in lymphocyte development and neoplasia within the immune system.

PMID- 12009900
TI  - Synthesis and biological evaluation in vitro of selective, high affinity peptide
      antagonists of human melanin-concentrating hormone action at human melanin
      concentrating hormone receptor 1.
AB  - Human melanin-concentrating hormone (hMCH) and many of its analogues are potent
      but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2
      (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of
      these receptors, selective antagonists are needed. In this study, analogues of Ac
      Arg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Gly(10)-Arg(11)-Val(12)-Tyr(13)-Arg(14)
      Pro(15)-Cys(16))-NH(2), a high affinity but nonselective agonist at hMCH-1R and
      hMCH-2R, were prepared and tested in binding and functional assays on cells
      expressing these receptors. In the new analogues, 5-aminovaleric acid (Ava) was
      incorporated in place of the Leu(9)-Gly(10) and/or Arg(14)-Pro(15) segments of
      the disulfide ring. Several of these compounds turned out to be high affinity
      antagonists selective for hMCH-1R. Moreover, even at micromolar concentrations,
      they were devoid of agonist potency at both hMCH receptors and not effective as
      hMCH-2R antagonists. For example, peptide 14, Gva(6)- cyclo(S-S)(Cys(7)-Met(8)
      Leu(9)-Gly(10)-Arg(11)-Val(12)-Tyr(13)-Ava(14,15)-Cys(16))-NH(2), (Gva = 5
      guanidinovaleric acid), was a full competitive hMCH-1R antagonist (IC(50) = 14
      nM, K(B) = 0.9 nM) with more than 1000-fold selectivity over hMCH-2R. Examination
      of various compounds with Ava in positions 9,10 and/or 14,15 revealed that the
      Leu(9)-Gly(10) and Arg(14)-Pro(15) segments of the disulfide ring are the
      principal structural elements determining hMCH-1R selectivity and ability to act
      as a hMCH-1R antagonist.

PMID- 12009901
TI  - Specific HIV-1 TAR RNA loop sequence and functional groups are required for human
      cyclin T1-Tat-TAR ternary complex formation.
AB  - Replication of human immunodeficiency virus requires Tat protein which activates
      elongation of RNA polymerase II transcription at the HIV-1 promoter through
      interaction with the cyclin T1 (CycT1) subunit of the positive transcription
      elongation factor complex (P-TEFb). Tat binds directly through its
      transactivation domain to the CycT1 subunit of the P-TEFb and induces loop
      sequence specific binding of the P-TEFb onto nascent HIV-1 TAR RNA. By using a
      gel electrophoresis method and a comprehensive set of TAR loop mutants, we have
      identified the sequence and structural determinants for high-affinity CycT1-Tat
      TAR ternary complex formation. Our results show that CycT1 and Tat binding to TAR
      RNA is highly cooperative, and a capacity of 85%, a Hill coefficient of 2.7, and
      a dissociation constant (K(D)) of 2.45 nM were observed. These results indicate
      that there are three binding sites on TAR RNA. CycT1 does not bind TAR RNA in the
      absence of Tat, and Tat binding to TAR, while detectable, is very inefficient in
      the absence of CycT1. It is conceivable that the CycT1-Tat heterodimer directly
      binds to TAR RNA in the U-rich RNA bulge region and this binding facilitates the
      interactions of the CycT1-Tat heterodimer at the other two sites in the RNA loop
      region. On the basis of our results, we suggest a model where CycT1 interacts
      with Tat protein and positions the protein complex to make contacts with the G34
      region of the loop sequence; G34 is critical for CycT1-Tat binding and forms a
      C30.G34 base pair. Two functional groups, O6 and N7, at nucleotide positions 32
      and 34 in the TAR loop are essential for CycT1-Tat interactions with TAR RNA. The
      identity of two nucleotides, U31 and G33, is not critical, but they contribute to
      the stabilization of the RNA-protein complex. The presence of a single-nucleotide
      bulge of A35 or C35 is essential for distortion of the backbone RNA structure as
      well as the accessibility of functional groups in the major groove of the double
      helical region. CycT1-Tat interaction with TAR RNA represents another example of
      the flexibility and complexity of RNA structure involved in protein recognition.

PMID- 12009902
TI  - Mutagenesis and mechanism-based inhibition of Streptococcus pyogenes Glu-tRNAGln
      amidotransferase implicate a serine-based glutaminase site.
AB  - The absence of Gln-tRNA synthetase in certain bacteria necessitates an alternate
      pathway for the production of Gln-tRNA(Gln): misacylated Glu-tRNA(Gln) is
      transamidated by a Gln-dependent amidotransferase (Glu-AdT) via catalysis of Gln
      hydrolysis, ATP hydrolysis, activation of Glu-tRNA(Gln), and aminolysis of
      activated tRNA by Gln-derived NH(3). As observed for other Gln-coupled
      amidotransferases, substrate binding, Gln hydrolysis, and transamidation by Glu
      AdT are tightly coordinated [Horiuchi, K. Y., Harpel, M. R., Shen, L., Luo, Y.,
      Rogers, K. C., and Copeland, R. A. (2001) Biochemistry 40, 6450-6457]. However,
      Glu-AdT does not employ an active-site Cys nucleophile for Gln hydrolysis, as is
      common in all other glutaminases: some Glu-AdT lack Cys, but all contain a
      conserved Ser (Ser176 in the A subunit of Streptococcus pyogenes Glu-AdT) within
      a sequence signature motif of Ser-based amidases. Our current results with S.
      pyogenes Glu-AdT support this characterization of Glu-AdT as a Ser-based
      glutaminase. Slow-onset (approximately 50 M(-1) s(-1)), tight-binding (t(1/2) >
      2.5 h for complex dissociation), Gln-competitive inhibition of the Glu
      tRNA(Gln)/ATP-independent glutaminase activity of Glu-AdT by gamma-Glu boronic
      acid is consistent with engagement of a Ser nucleophile in the glutaminase active
      site. Conversion to rapidly reversible, yet still potent (K(i) = 73 nM) and Gln
      competitive, inhibition under full transamidation conditions mirrors the coupling
      between Gln hydrolysis and aminolysis reactions during productive transamidation.
      Site-directed replacement of Ser176 by Ala abolishes glutaminase and Gln
      dependent transamidase activities of Glu-AdT (>300-fold), but retains a wild-type
      level of NH(3)-dependent transamidation activity. These results demonstrate the
      essentiality of Ser176 for Gln hydrolysis, provide additional support for
      coordinated coupling of Gln hydrolysis and transamidase transition states during
      catalysis, and validate glutaminase-directed inhibition of Glu-AdT as a route for
      antimicrobial chemotherapy.

PMID- 12009903
TI  - Electrostatic interactions at the C-terminal domain of nucleoplasmin modulate its
      chromatin decondensation activity.
AB  - The chromatin decondensation activity, thermal stability, and secondary structure
      of recombinant nucleoplasmin, of two deletion mutants, and of the protein
      isolated from Xenopus oocytes have been characterized. As previously reported,
      the chromatin decondensation activity of recombinant, unphosphorylated
      nucleoplasmin is almost negligible. Our data show that deletion of 50 residues at
      the C-terminal domain of the protein, containing the positively charged nuclear
      localization sequence, activates its chromatin decondensation ability and
      decreases its stability. Interestingly, both the decondensation activity and
      thermal stability of this deletion mutant resemble those of the phosphorylated
      protein isolated from Xenopus oocytes. Deletion of 80 residues at the C-terminal
      domain, containing the above-mentioned positively charged region and a poly(Glu)
      tract, inactivates the protein and increases its thermal stability. These
      findings, along with the effect of salt on the thermal stability of these
      proteins, suggest that electrostatic interactions between the positive nuclear
      localization sequence and the poly(Glu) tract, at the C-terminal domain, modulate
      protein activity and stability.

PMID- 12009904
TI  - N-hydroxy-4-aminobiphenyl-DNA binding in human p53 gene: sequence preference and
      the effect of C5 cytosine methylation.
AB  - 4-Aminobiphenyl (4-ABP) is a major etiological agent for human bladder cancer.
      Metabolically activated 4-ABP is able to interact with DNA to form adducts that
      may induce mutations and initiate carcinogenesis. Thirty to sixty percent of
      bladder cancer has a mutation in the tumor suppressor p53 gene, and the
      mutational spectrum bears unique features. To date the DNA binding spectrum of 4
      ABP in the p53 gene is not known due to the lack of methodology to detect 4-ABP
      DNA adducts at nucleotide sequence level. We have found that UvrABC nuclease, a
      nucleotide excision repair complex isolated from Escherichia coli, is able to
      incise specifically and quantitatively DNA fragments modified with N-hydroxy-4
      aminobiphenyl (N-OH-4-ABP), an activated intermediate of 4-ABP. Using the UvrABC
      nuclease incision method, we mapped the binding spectrum of N-OH-4-ABP in DNA
      fragments containing exons 5, 7, and 8 of the human p53 gene and also determined
      the effect of C5 cytosine methylation on N-OH-4-ABP-DNA binding. We found that
      codon 285, a mutational hotspot at a non-CpG site in bladder cancer, is the
      preferential binding site for N-OH-4-ABP. We also found that C5 cytosine
      methylation greatly enhanced N-OH-4-ABP binding at CpG sites, and that two
      mutational hotspots at CpG sites, codons 175 and 248, became preferential binding
      sites for N-OH-4-ABP only after being methylated. These results suggest that both
      the unique DNA binding specificity of 4-ABP and cytosine methylation contribute
      to the mutational spectrum of the p53 gene in human bladder cancer.

PMID- 12009905
TI  - Aggregation of granulocyte colony stimulating factor under physiological
      conditions: characterization and thermodynamic inhibition.
AB  - We have investigated the aggregation of recombinant human granulocyte colony
      stimulating factor (rhGCSF), a protein that rapidly aggregates and precipitates
      at pH 6.9 and 37 degrees C. We observed that native monomeric rhGCSF reversibly
      forms a dimer under physiological conditions and that this dimeric species does
      not participate in the irreversible aggregation process. Sucrose, a thermodynamic
      stabilizer, inhibits the aggregation of rhGCSF. We postulate that sucrose acts by
      reducing the concentration of structurally expanded species, consistent with the
      hypothesis that preferential exclusion favors most compact species in the native
      state ensemble. Thermodynamic stability data from unfolding curves and hydrogen
      deuterium exchange experimental results support the above hypothesis. Thus, the
      strategy of stabilizing the native state of the protein under physiological
      conditions using thermodynamic stabilizers, especially ligands binding with high
      affinity to the native state, is expected to protect against protein aggregation
      occurring under such nonperturbing solution conditions.

PMID- 12009906
TI  - The missing link in the fungal L-arabinose catabolic pathway, identification of
      the L-xylulose reductase gene.
AB  - The fungal L-arabinose pathway consists of five enzymes, aldose reductase, L
      arabinitol 4-dehydrogenase, L-xylulose reductase, xylitol dehydrogenase, and
      xylulokinase. All the genes encoding the enzymes of this pathway are known except
      for that of L-xylulose reductase (EC 1.1.1.10). We identified a gene encoding
      this enzyme from the filamentous fungus Trichoderma reesei (Hypocrea jecorina).
      The gene was named lxr1. It was overexpressed in the yeast Saccharomyces
      cerevisiae, and the enzyme activity was confirmed in a yeast cell extract.
      Overexpression of all enzymes of the L-arabinose pathway in S. cerevisiae led to
      growth of S. cerevisiae on L-arabinose; i.e., we could show that the pathway is
      active in a heterologous host. The lxr1 gene encoded a protein with 266 amino
      acids and a calculated molecular mass of 28 428 Da. The LXRI protein is an NADPH
      specific reductase. It has activity with L-xylulose, D-xylulose, D-fructose, and
      L-sorbose. The highest affinity is toward L-xylulose (K(m) = 16 mM). In the
      reverse direction, we found activity with xylitol, D-arabinitol, D-mannitol, and
      D-sorbitol. It requires a bivalent cation for activity. It belongs to the protein
      family of short chain dehydrogenases. The enzyme is catalytically similar and
      homologous in sequence to a D-mannitol:NADP 2-dehydrogenase (EC 1.1.1.138).

PMID- 12009907
TI  - Spectroscopic characterization and O2 reactivity of the trinuclear Cu cluster of
      mutants of the multicopper oxidase Fet3p.
AB  - Fet3p is a multicopper oxidase that uses four copper ions (one type 1, one type
      2, and one type 3 binuclear site) to couple substrate oxidation to the reduction
      of O(2) to H(2)O. The type 1 Cu site shuttles electrons between the substrate and
      the type 2/type 3 Cu sites which form a trinuclear Cu cluster that is the active
      site for O(2) reduction. This study extends the spectroscopic and reactivity
      studies that have been conducted with type 1-substituted Hg (T1Hg) laccase to
      Fet3p and a mutant of Fet3p in which the trinuclear Cu cluster is perturbed. To
      examine the reaction between the trinuclear Cu cluster and O(2), the type 1 Cu
      Cys(484) was mutated to Ser, resulting in a type 1-depleted (T1D) form of the
      enzyme. Additional His to Gln mutations were made at the trinuclear cluster to
      further probe specific contributions to reactivity. One of these mutants
      (His(126)Gln) produces the first stable but perturbed trinuclear Cu cluster
      (T1DT3' Fet3p). Spectroscopic characterization (absorption, circular dichroism,
      magnetic circular dichroism, and electron paramagnetic resonance) of the resting
      trinuclear sites in T1D and T1DT3' Fet3p reveal that the His(126)Gln mutation
      changes the electronic structure of both the type 3 and type 2 Cu sites. The
      trinuclear clusters in T1D and T1DT3' Fet3p react with O(2) to produce peroxide
      intermediates analogous to that observed in T1Hg laccase. Spectroscopic data on
      the peroxide intermediates in the three forms provide further insight into the
      structure of this intermediate. In T1D Fet3p, the decay of this peroxide
      intermediate is pH-dependent, and the rate of decay is 10-fold higher at low pH.
      In T1DT3' Fet3p, the decay of the peroxide intermediate is pH-independent and is
      slow at all pH's. This change in the pH dependence provides new insight into the
      mechanism of intermediate decay involving reductive cleavage of the O-O bond.

PMID- 12009908
TI  - Structural organization of the fibrin(ogen) alpha C-domain.
AB  - We hypothesized that the alpha C-domain of human fibrinogen (residues hA alpha
      221-610) and of other species consists of a compact COOH-terminal region (hA
      alpha 392-610) and a flexible NH(2)-terminal connector region (hA alpha 221-391)
      which may contain some regular structure [Weisel and Medved (2001) Ann. N.Y.
      Acad. Sci. 936, 312-327]. To test this hypothesis, we expressed in E. coli
      recombinant fragments corresponding to the full-length human alpha C-domain and
      its NH(2)- and COOH-terminal regions as well as their bovine counterparts, bA
      alpha 224-568, bA alpha 224-373, and bA alpha 374-568(538), respectively, and
      tested their folding status by fluorescence spectroscopy, circular dichroism
      (CD), and differential scanning calorimetry (DSC). All three methods revealed
      heat-induced unfolding transitions in the full-length bA alpha 224-568 and its
      two COOH-terminal fragments, indicating that the COOH-terminal portion of the
      bovine alpha C-domain is folded into a compact cooperative structure. Similar
      results were obtained by CD and DSC with the full-length and the COOH-terminal
      h392-610 human fragments. The NH(2)-terminal fragments of both species, b224-373
      and h221-392, did not exhibit any sign of a compact structure. However, their
      heat capacity functions, CD spectra, and temperature dependence of ellipticity at
      222 nm were typical for peptides in the extended helical poly(L-proline) type II
      conformation (PPII), suggesting that they contain this type of regular structure.
      This is consistent with the presence of proline-rich tandem repeats in the
      sequence of both bovine and human connector regions. These results indicate that
      both bovine and human fibrinogen alpha C-domains consist of a compact globular
      cooperative unit attached to the bulk of the molecule by an extended NH(2)
      terminal connector region with a PPII conformation.

PMID- 12009909
TI  - R150A mutant of F TraI relaxase domain: reduced affinity and specificity for
      single-stranded DNA and altered fluorescence anisotropy of a bound labeled
      oligonucleotide.
AB  - F factor TraI is a helicase and a single-stranded DNA nuclease ("relaxase")
      essential for conjugative DNA transfer. A TraI domain containing relaxase
      activity, TraI36, was generated previously. Substituting Ala for Arg150 (R150A)
      of TraI36 reduces in vitro relaxase activity. The mutant has reduced affinity,
      relative to wild type, for a 3'-TAMRA-labeled 22-base single-stranded
      oligonucleotide. While both R150A and wild-type TraI36 bind oligonucleotide, only
      wild type increases steady-state fluorescence anisotropy of the labeled 22-base
      oligonucleotide upon binding. In contrast, binding by either protein increases
      steady-state anisotropy of a 3'-TAMRA-labeled 17-base oligonucleotide. Time
      resolved intensity data for both oligonucleotides, bound and unbound, require
      three lifetimes for adequate fits, at least one more than the fluorophore alone.
      The preexponential amplitude for the longest lifetime increases upon binding.
      Time-resolved anisotropy data for both oligonucleotides, bound and unbound,
      require two rotational correlation times for adequate fits. The longer
      correlation time increases upon protein binding. Correlation times for the
      protein-bound 17-base oligonucleotide are similar for both proteins, with the
      longer correlation time in the range of molecular tumbling of the protein-DNA
      complex. In contrast, protein binding causes less dramatic increases in
      correlation times for the 22-base oligonucleotide relative to the 17-base
      oligonucleotide. Binding studies indicate that R150 contributes to recognition of
      bases immediately 3' to the DNA cleavage site, consistent with the apparent
      proximity of R150 and the 3' oligonucleotide end. Models in which the R150A
      substitution alters single-stranded DNA flexibility at the oligonucleotide 3' end
      or affects fluorophore-DNA or fluorophore-protein interactions are discussed.

PMID- 12009910
TI  - Structures of the cuprous-thiolate clusters of the Mac1 and Ace1 transcriptional
      activators.
AB  - X-ray absorption spectroscopy on the minimal copper-regulatory domains of the two
      copper-regulated transcription factors (Ace1 and Mac1) in Saccharomyces
      cerevisiae revealed the presence of a remarkably similar polycopper cluster in
      both proteins. The Cu-regulatory switch motif of Mac1 consisting of the C
      terminal first Cys-rich motif, designated the C1 domain, binds four Cu(I) ions as
      does the Cu-regulatory domain of Ace1. The four Cu(I) ions are bound to each
      molecule in trigonal geometry. An extended X-ray absorption fine structure
      (EXAFS) arising from outer-shell Cu...Cu interactions at 2.7 and 2.9 A was
      apparent in each Cu(I) complex indicative of a polycopper cluster. The intensity
      of the 2.9 A Cu...Cu backscatter peak, apparently diminished by partial
      cancellation, dominates the EXAFS. The results suggest that CuAce1 and CuMac1(C1)
      contain somewhat distorted forms of a known [Cu(4)-S(6)] cage in which a core of
      Cu atoms forming an approximate tetrahedron is bound by bridging thiolates above
      each of the six edges. The tetracopper clusters bound by Ace1 and Mac1 differ in
      that the Ace1 cluster is coordinated entirely by cysteinyl thiolate, whereas the
      cysteine-deficient Mac1 cluster appears to consist of a Cu(4)(S-Cys)(5)(N-His)
      cluster with a bridging histidyl-derived nitrogen.

PMID- 12009911
TI  - Phosphorescence and optically detected magnetic resonance of 4',6-diamidino-2
      phenylindole (DAPI) and its complexes with [d(CGACGTCG)]2 and [d(GGCCAATTGG)]2.
AB  - Phosphorescence and optical detection of magnetic resonance (ODMR) is used to
      study the excited triplet state of 4',6-diamidino-2-phenyl indole (DAPI) and its
      complexes with the oligonucleotides [d(CGACGTCG)](2) and [d(GGCCAATTGG)](2),
      where binding occurs by intercalation between GC base pairs and by minor groove
      insertion, respectively. Weaker binding of DAPI to phosphate is also detected,
      and the triplet state of this complex is characterized. Intercalation with
      [d(CGACGTCG)](2) produces a phosphorescence redshift, while groove binding with
      [d(GGCCAATTGG)](2) leads to a blueshift. Both binding modes give rise to a small
      decrease in the zero-field splitting (zfs) of the DAPI triplet state. The largest
      redshift and zfs decrease are found for the phosphate complex. The
      phosphorescence lifetimes are shorter by an order of magnitude than that of
      indole or tryptophan as expected for the lower triplet state energy, E(00), of
      DAPI. The lifetimes agree well with a correlation with E(00) introduced by
      Siebrand [Siebrand, W. (1966) J. Chem. Phys. 44, 4055-4057] except for the
      [d(GGCCAATTGG)](2) minor groove complex with a lifetime that is about 20% too
      long. The longer lifetime is attributed to distortion of the amidino groups in
      this complex, resulting in less efficient intersystem crossing.

PMID- 12009912
TI  - Electrostatic interactions in an integral membrane protein.
AB  - The effects of charge-charge interactions on the midpoint reduction potential
      (E(m)()) of the primary electron donor (P) in the photosynthetic reaction center
      of Rhodobacter sphaeroides were investigated by introducing mutations of
      ionizable amino acids at selected sites. The mutations were designed to alter the
      electrostatic environment of P, a bacteriochlorophyll dimer, without greatly
      affecting its structure or molecular orbitals. Two arginine residues at
      homologous positions in the L and M subunits [residues (L135) and (M164)], Asp
      (L155), Tyr (L164), and Cys (L247) were changed independently. Arginine (L135)
      was replaced by Lys, Leu, Gln, or Glu; Arg (M164), by Leu or Glu; Asp (L155), by
      Asn; Tyr (L164), by Phe; and Cys (L247), by Lys or Asp. The R(L135)E/C(L247)K
      double mutant also was made. The shift in the E(m)() of P/P(+) was measured in
      each mutant and was compared with the effect predicted by electrostatics
      calculations using several different computational approaches. A simple distance
      dependent dielectric screening factor reproduced the effects remarkably well. By
      contrast, microscopic methods that considered the reaction field in the protein
      and solvent but did not include explicit counterions overestimated the changes in
      the E(m)() considerably. Including counterions for the charged residues reduced
      the calculated effects of the mutations in molecular dynamics calculations. The
      results show that electrostatic interactions of P with ionizable amino acid
      residues are strongly screened, and suggest that counterions make major
      contributions to this screening. The screening also could reflect penetration of
      water or other relaxations not taken into account because of incomplete sampling
      of configurational space.

PMID- 12009913
TI  - Changes in hydrogen bonding and environment of tryptophan residues on helix F of
      bacteriorhodopsin during the photocycle: a time-resolved ultraviolet resonance
      Raman study.
AB  - Protein structural changes during the photocycle of bacteriorhodopsin were
      examined by time-resolved ultraviolet resonance Raman (UVRR) spectroscopy. Most
      of the 244-nm UVRR difference signals of Trp were assigned to either Trp182 or
      Trp189 using the Trp182 --> Phe and Trp189 --> Phe mutants. The W17 mode of
      Trp182 shows a wavenumber downshift in the M(1) --> M(2) transition, indicating
      an increase in hydrogen bonding strength at the indole nitrogen. On the other
      hand, Trp189 shows Raman intensity increases of the W16 and W18 modes ascribable
      to an increased hydrophobic interaction. These observations suggest that the tilt
      of helix F, which ensures that reprotonation of the Schiff base is from the
      cytoplasmic side, occurs in the M(1) --> M(2) transition. In the M(2) --> N
      transition, the environment of Trp189 returns to the initial state, whereas the
      hydrophobic interaction of Trp182 decreases drastically. The decrease in
      hydrophobic interaction of Trp182 in the N state suggests an invasion of water
      molecules that promote the proton transfer from Asp96 to the Schiff base.
      Structural reorganization of the protein after the tilt of helix F may be
      important for efficient reprotonation of the Schiff base.

PMID- 12009914
TI  - A pharaonis phoborhodopsin mutant with the same retinal binding site residues as
      in bacteriorhodopsin.
AB  - pharaonis phoborhodopsin (ppR, also called pharaonis sensory rhodopsin II, psR
      II) is a photoreceptor for negative phototaxis in Natronobacterium pharaonis. ppR
      has a blue-shifted absorption maximum (500 nm) relative those of other archaeal
      rhodopsins such as the proton-pump bacteriorhodopsin (BR; 570 nm). Among the 25
      amino acids that are within 5 A of the retinal chromophore, 10 are different in
      BR and ppR, and they are presumed to be crucial in determining the color of their
      chromophores. However, the spectral red shift in a multiple mutant of ppR, in
      which the retinal binding site was made similar to that of BR (BR/ppR), was
      smaller than 40% (lambda(max) = 524 nm) than expected. In the paper presented
      here, we report on low-temperature Fourier transform infrared (FTIR) spectroscopy
      of BR/ppR, and compare the infrared spectral changes before and after
      photoisomerization with those for ppR and BR. The C[bond]C stretch and hydrogen
      out-of-plane (HOOP) vibrations of BR/ppR were similar to those of BR, suggesting
      that the surrounding protein moiety of BR/ppR becomes like BR. However, BR/ppR
      exhibited a unique IR band regarding the hydrogen bond of the protonated Schiff
      base. It has been known that ppR has a stronger hydrogen bond for the Schiff base
      than BR as judged from the frequency difference between their C[double bond]NH
      and C[double bond]ND stretches. We now find that replacement of the 10 amino
      acids of BR with ppR (BR/ppR) does not weaken the hydrogen bond of the Schiff
      base. Rather, the hydrogen bond in BR/ppR is stronger than that in the native
      ppR. We conclude that the principal factor of the smaller than expected opsin
      shift in BR/ppR is the strong association of the Schiff base with the surrounding
      counterion complex.

PMID- 12009915
TI  - EPR studies on a stable sulfinyl radical observed in the iron-oxygen
      reconstituted Y177F/I263C protein R2 double mutant of ribonucleotide reductase
      from mouse.
AB  - Ribonucleotide reductase (RNR) catalyzes the biosynthesis of
      deoxyribonucleotides. The active enzyme contains a diiron center and a tyrosyl
      free radical required for enzyme activity. The radical is located at Y177 in the
      R2 protein of mouse RNR. The radical is formed concomitantly with the mu-oxo
      bridged diferric center in a reconstitution reaction between ferrous iron and
      molecular oxygen in the protein. EPR at 9.6 and 285 GHz was used to investigate
      the reconstitution reaction in the double-mutant Y177F/I263C of mouse protein R2.
      The aim was to produce a protein-linked radical derived from the Cys residue in
      the mutant protein to investigate its formation and characteristics. The mutation
      Y177F hinders normal radical formation at Y177, and the I263C mutation places a
      Cys residue at the same distance from the iron center as Y177 in the native
      protein. In the reconstitution reaction, we observed small amounts of a transient
      radical with a probable assignment to a peroxy radical, followed by a stable
      sulfinyl radical, most likely located on C263. The unusual radical stability may
      be explained by the hydrophobic surroundings of C263, which resemble the
      hydrophobic pocket surrounding Y177 in native protein R2. The observation of a
      sulfinyl radical in RNR strengthens the relationship between RNR and another free
      radical enzyme, pyruvate formate-lyase, where a similar relatively stable
      sulfinyl radical has been observed in a mutant. Sulfinyl radicals may possibly be
      considered as stabilized forms of very short-lived thiyl radicals, proposed to be
      important intermediates in the radical chemistry of RNR.

PMID- 12009916
TI  - The A167Y mutation converts the herpes simplex virus type 1 thymidine kinase into
      a guanosine analogue kinase.
AB  - The thymidine (dThd) kinase (TK) encoded by herpes simplex virus type 1 (HSV-1)
      is not only endowed with dThd kinase, but also with thymidylate (dTMP) kinase and
      2'-deoxycytidine (dCyd) kinase (dCK) activity. HSV-1 TK also recognizes a variety
      of antiherpetic guanine nucleoside analogues such as acyclovir (ACV), ganciclovir
      (GCV), lobucavir (LBV), penciclovir (PCV), and others (i.e., A5021). Site
      directed mutagenesis of the highly conserved Ala-167 to Tyr in HSV-1 TK
      completely abolished TK, dTMP-K, and dCK activity, but maintained ACV-, GCV-, LBV
      , PCV-, and A5021-phosphorylating capacity. A variety of 5-substituted pyrimidine
      nucleoside substrates, but also a number of selective HSV-1 TK inhibitors
      structurally related to thymine lost significant binding affinity for the mutant
      enzyme and did not markedly compete with GCV phosphorylation by the mutant
      enzyme. These findings could be explained by computer-assisted modeling data that
      revealed steric hindrance of the pyrimidine ring in the HSV-1 TK active site by
      the large 4-hydroxybenzyl ring of 167-Tyr, while the positioning of the purine
      ring of guanine-based HIV-1 TK substrates in the active site was kept virtually
      unaltered. Surprisingly, the efficiency of conversion the antiherpetic 2'
      deoxyguanosine analogues ACV, GCV, LBV, PCV, and A5021 to their phosphorylated
      forms by the A167Y mutant HSV-1 TK was far more pronounced than for the wild-type
      enzyme. Therefore, the single A167Y mutation converts the wild-type HSV-1 TK from
      a predominantly pyrimidine nucleos(t)ide kinase into a virtually exclusive purine
      (guanine) nucleoside analogue kinase.

PMID- 12009917
TI  - Electrochemical and functional characterization of the proline dehydrogenase
      domain of the PutA flavoprotein from Escherichia coli.
AB  - The multifunctional PutA flavoprotein from Escherichia coli is a peripherally
      membrane-bound enzyme that has both proline dehydrogenase (PDH) and Delta(1)
      pyrroline-5-carboxylate dehydrogenase (P5CDH) activities. In addition to its
      enzymatic functions, PutA displays DNA-binding activity and represses proline
      catabolism by binding to the control region DNA of the put regulon (put
      intergenic DNA). Presently, information on structure-function relationships for
      PutA is derived from primary structure analysis. To gain further insight into the
      functional organization of PutA, our objective is to dissect PutA into different
      domains and to characterize them separately. Here, we report the characterization
      of a bifunctional proline dehydrogenase (PutA(669)) that contains residues 1-669
      of the PutA protein. PutA(669) purifies as a dimer and has a PDH specific
      activity that is 4-fold higher than that of PutA. As anticipated, PutA(669) lacks
      P5CDH activity. At pH 7.5, an E(m) (E-FAD/E-FADH(-)) of -0.091 V for the two
      electron reduction of PutA(669)-bound FAD was determined by potentiometric
      titrations, which is 15 mV more negative than the E(m) for PutA-bound FAD. The pH
      behavior of the E(m) for PutA(669)-bound FAD was measured in the pH range 6.5-9.0
      at 25 degrees C and exhibited a 0.03 V/pH unit slope. Analysis of the DNA and
      membrane-binding properties of PutA(669) shows that it binds specifically to the
      put intergenic control DNA with a binding affinity similar to that of PutA. In
      contrast, we did not observe functional association of PutA(669) with membrane
      vesicles. We conclude that PutA(669) has FAD-binding and DNA-binding properties
      comparable to those of PutA but lacks a membrane-binding domain necessary for
      stable association with the membrane.

PMID- 12009918
TI  - Residual electrostatic effects in the unfolded state of the N-terminal domain of
      L9 can be attributed to nonspecific nonlocal charge-charge interactions.
AB  - Residual electrostatic interactions in the unfolded state of the N-terminal
      domain of L9 (NTL9) were found by Kuhlman et al. [(1999) Biochemistry 38, 4896
      4903]. These residual interactions are analyzed here by the Gaussian-chain model
      [Zhou, H.-X. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 3569-3574]. The original
      model is made more realistic by replacing "standard" model-compound pK(a) values
      for ionizable groups by those measured by Kuhlman et al. in peptide fragments of
      NTL9. The predicted pH dependence of the unfolding free energy is in agreement
      with experiment over the pH range of 1-7 at ionic strengths of 100 and 750 mM.
      This indicates that the residual electrostatic effects in the unfolded state of
      NTL9 can be attributed to nonspecific nonlocal charge-charge interactions.

PMID- 12009919
TI  - Folding and conformational consequences of glycine to alanine replacements at
      different positions in a collagen model peptide.
AB  - The collagen model peptide T1-892 includes a C-terminal nucleation domain, (Gly
      Pro-Hyp)(4), and an N-terminal (Gly-X-Y)(6) sequence taken from type I collagen.
      In osteogenesis imperfecta (OI) and other collagen diseases, single base
      mutations often convert one Gly to a larger residue, and T1-892 homologues
      modeling such mutations were synthesized with Gly to Ala substitutions in either
      the (Gly-Pro-Hyp)(4) domain, Gly25Ala, or the (Gly-X-Y)(6) domain, Gly10Ala. CD
      and NMR studies show the Gly10Ala peptide forms a normal triple-helix at the C
      terminal end and propagates from the C- to the N-terminus until the Gly --> Ala
      substitution is encountered. At this point, triple-helix folding is terminated
      and cannot be reinitiated, leaving a nonhelical N-terminus. A decreased thermal
      stability is observed as a result of the shorter length of the triple-helix. In
      contrast, introduction of the Gly to Ala replacement at position 25, in the
      nucleation domain, shifts the monomer/trimer equilibrium toward the monomer form.
      The increased monomer and lower trimer populations are reflected in the dramatic
      decrease in triple-helix content and stability. Unlike the Ala replacement at
      position 10, the Ala substitution in the (Gly-Pro-Hyp)(4) region can still be
      incorporated into a triple-helix, but at a greatly decreased rate of folding,
      since the original efficient nucleation site is no longer operative. The specific
      consequences of Gly to Ala replacements in two distinctive sequences in this
      triple-helical peptide may help clarify the variability in OI clinical severity
      resulting from mutations at different sites along type I collagen chains.

PMID- 12009920
TI  - Ivermectin and nodulisporic acid receptors in Drosophila melanogaster contain
      both gamma-aminobutyric acid-gated Rdl and glutamate-gated GluCl alpha chloride
      channel subunits.
AB  - 35S-labeled derivatives of the insecticides nodulisporic acid and ivermectin were
      synthesized and demonstrated to bind with high affinity to a population of
      receptors in Drosophila head membranes that were previously shown to be
      associated with a glutamate-gated chloride channel. Nodulisporic acid binding was
      modeled as binding to a single population of receptors. Ivermectin binding was
      composed of at least two kinetically distinct receptor populations, only one of
      which was associated with nodulisporic acid binding. The binding of these two
      ligands was modulated by glutamate, ivermectin, and antagonists of invertebrate
      gamma-aminobutyric acid (GABA)ergic receptors. Because solubilized nodulisporic
      acid and ivermectin receptors comigrated as 230-kDa complexes by gel filtration,
      antisera specific for both the Drosophila glutamate-gated chloride channel
      subunit GluCl alpha (DmGluCl alpha) and the GABA-gated chloride channel subunit
      Rdl (DmRdl) proteins were generated and used to examine the possible coassembly
      of these two subunits within a single receptor complex. DmGluCl alpha antibodies
      immunoprecipitated all of the ivermectin and nodulisporic acid receptors
      solubilized by detergent from Drosophila head membranes. DmRdl antibodies also
      immunoprecipitated all solubilized nodulisporic receptors, but only approximately
      70% of the ivermectin receptors. These data suggest that both DmGluCl alpha and
      DmRdl are components of nodulisporic acid and ivermectin receptors, and that
      there also exists a distinct class of ivermectin receptors that contains the
      DmGluCl alpha subunit but not the DmRdl subunit. This co-association of DmGluCl
      alpha and DmRdl represents the first biochemical and immunological evidence of
      coassembly of subunits from two different subclasses of ligand-gated ion channel
      subunits.

PMID- 12009921
TI  - Characterization of a viroid-derived RNA promoter for the DNA-dependent RNA
      polymerase from Escherichia coli.
AB  - This paper attributes a novel function, namely, that of transcriptional promoter,
      to the self-complementary, self-cleaving hammerhead RNA sequences found in RNA
      derived from the peach latent mosaic viroid (PLMVd). The features of this RNA
      promoter, which adopts a hairpin structure that can be utilized by Escherichia
      coli RNA polymerase (RNAP) for in vitro transcription, that trigger the RNAP
      driven transcription and are responsible for the specific initiation of synthesis
      are described. The essential requirement for initiation is a basepaired uridine
      adjacent to the loop. The presence of a loop composed of at least six nucleotides
      connected to a relatively unstable stem significantly increases the level of
      initiation. Finally, we present several insights into the mechanism of the RNAP
      which reveal that it behaves differently with an RNA template as compared to a
      DNA one.

PMID- 12009924
TI  - Facile synthesis of thiol-reactive Cy3 and Cy5 derivatives with enhanced water
      solubility.
AB  - The cyanine dyes Cy3 and Cy5 have proven valuable in numerous applications
      involving conjugation with proteins. Practical syntheses of lysine-selective,
      succinimidyl ester derivatives of these dyes have been published, and
      succinimidyl esters are commercially available. However, the published syntheses
      of cysteine-selective derivatives produce relatively low yields from expensive
      starting materials, or produce molecules with marginal water solubility for
      protein labeling. We report here facile syntheses (four steps, >50% overall
      yield) of iodoacetamide, sulfhydryl-reactive derivatives of the Cy3 and Cy5
      fluorophores. These novel derivatives have good water solubility (>2.5 mM) and
      bear only one reactive side chain, reducing possible protein cross-linking
      encountered with previous derivatives.

PMID- 12009925
TI  - Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as
      target-specific photosensitizer.
AB  - To target tumors overexpressing low-density lipoprotein receptors (LDLr), a
      pyropheophorbide cholesterol oleate conjugate was synthesized and successfully
      reconstituted into the low-density lipoprotein (LDL) lipid core. Laser scanning
      confocal microscopy studies demonstrated that this photosensitizer-reconstituted
      LDL can be internalized via LDLr by human hepatoblastoma G(2) (HepG(2)) tumor
      cells.

PMID- 12009926
TI  - Effect of heme structure on O(2)-binding properties of human serum albumin-heme
      hybrids: intramolecular histidine coordination provides a stable O(2)-adduct
      complex.
AB  - 5,10,15,20-Tetrakis[(alpha,alpha,alpha,alpha-o
      pivaloylamino)phenyl]porphinatoiron(II) and 5,10,15,20
      tetrakis([alpha,alpha,alpha,alpha-o-(1
      methylcyclohexanoylamino)]phenyl)porphinatoiron(II) complexes bearing a
      covalently bound 8-(2-methyl-1-imidazolyl)octanoyloxymethyl or 4-(methyl-L
      histidinamido)butanoyloxymethyl side-chain [FeRP(B) series: R = piv or cyc, B =
      Im or His] have been synthesized. The histidine-bound derivatives [FepivP(His),
      FecycP(His)] formed five N-coordinated high-spin iron(II) complexes in organic
      solvents under an N(2) atmosphere and showed large O(2)-binding affinities in
      comparison to those of the 2-methylimidazole-bound analogues [FepivP(Im),
      FecycP(Im)] due to the low O(2)-dissociation rate constants. On the contrary, the
      difference in the fence groups around the O(2)-coordination site (pivaloyl or 1
      methylhexanoyl) did not significantly influence to the O(2)-binding parameters.
      These four porphinatoiron(II)s were efficiently incorporated into recombinant
      human serum albumin (rHSA), thus providing the synthetic hemoprotein, the albumin
      heme hybrid [rHSA-FeRP(B)]. An rHSA host absorbs a maximum of eight FeRP(B)
      molecules in each case. The obtained rHSA-FeRP(B) can reversibly bind and release
      O(2) under physiological conditions (in aqueous media, pH 7.3, 37 degrees C) like
      hemoglobin and myoglobin. As in organic solutions, the difference in the fence
      groups did not affect their O(2)-binding parameters, but the axial histidine
      coordination significantly increased the O(2)-binding affinity, which is again
      ascribed to the low O(2)-dissociation rates. The most remarkable effect of the
      heme structure appeared in the half-life (tau(1/2)) of the O(2)-adduct complex.
      The dioxygenated rHSA-FecycP(His) showed an unusually long lifetime (tau(1/2): 25
      h at 37 degrees C) which is ca. 13-fold longer than that of rHSA-FepivP(Im).

PMID- 12009927
TI  - 3-methyladenine-DNA glycosylase II: the crystal structure of an AlkA-hypoxanthine
      complex suggests the possibility of product inhibition.
AB  - Escherichia coli (E. coli) protein 3-methyladenine-DNA glycosylase II (AlkA)
      functions primarily by removing alkylation damage from duplex and single stranded
      DNA. A crystal structure of AlkA was refined to 2.0 A resolution. This structure
      in turn was used to refine an AlkA-hypoxanthine (substrate) complex structure to
      2.4 A resolution. The complex structure shows hypoxanthine located in AlkA's
      active site stacked between residues W218 and Y239. The structural analysis of
      the AlkA and AlkA-hypoxanthine structures indicate that free hypoxanthine binding
      in the active site may inhibit glycosylase activity.

PMID- 12009928
TI  - Monoclonal antibodies that recognize minimal differences in the three-dimensional
      structures of metal-chelate complexes.
AB  - Immunization of BALB/c mice with a cadmium-chelate-protein conjugate resulted in
      the isolation of two hybridoma cell lines (A4 and E5) that synthesized antibodies
      with different variable regions, but similar metal-chelate affinity. The ability
      of these two monoclonal antibodies to interact with 12 different metal-chelate
      complexes was studied using the KinExA 3000 immunoassay instrument. The two
      antibodies showed the highest affinity for cadmium and mercury complexes of
      ethylenediamine N,N,N',N'-tetraacetic acid (EDTA). The E5 antibody bound to EDTA
      complexes of cadmium and mercury with equilibrium dissociation constants (K(d))
      of 1.62 x 10(-)(9) M and 3.64 x 10(-)(9) M, respectively. The corresponding
      values for the A4 antibody were 14.7 x 10(-)(9) M and 3.56 x 10(-)(9) M. Addition
      of a cyclohexyl ring to the EDTA backbone increased the affinity of E5 for the
      metal-chelate haptens, while decreasing the binding of A4 to the same haptens.
      Based on available crystal structures, molecular models were constructed for five
      different divalent metal-chelate complexes. The models were compared to determine
      structural features of the haptens that may influence antibody recognition.
      Difference distance matrixes were used to identify areas of the metal-chelate
      haptens that differed in three-dimensional space. Antibody affinity correlated
      well with the extent of total structural difference for these metal-EDTA
      complexes.

PMID- 12009929
TI  - Synthesis, characterization, and application of cy-dye- and alexa-dye-labeled
      hongotoxin(1) analogues. The first high affinity fluorescence probes for voltage
      gated K+ channels.
AB  - Hongotoxin(1) (HgTX(1)), a 39-residue peptide recently isolated from the venom of
      Centruroides limbatus, blocks the voltage-gated K+ channels K(v)1.1, K(v)1.2, and
      K(v)1.3 at picomolar toxin concentrations (Koschak, A., Bugianesi, R. M.,
      Mitterdorfer, J., Kaczorowski, G. J., Garcia, M. L., and Knaus, H. G. (1998) J.
      Biol. Chem. 273, 2639-2644). In this report, we determine the three-dimensional
      structure of HgTX(1) using NMR spectroscopy (PDB-code: 1HLY). HgTX(1) was found
      to possess a structure similar to previously characterized K+ channel toxins
      (e.g. margatoxin) consisting of a three-stranded antiparallel beta-sheet
      (residues 2-4, 26-30, and 33-37) and a helical conformation (part 3(10) helix and
      part alpha helix; residues 10-20). Due to the importance of residue Lys-28 for
      high-affinity interaction with the respective channels, lysine-reactive
      fluorescence dyes cannot be used to label wild-type HgTX(1). On the basis of
      previous studies (see above) and our NMR data, a HgTX(1) mutant (HgTX(1)-A19C)
      was engineered, expressed, and purified. HgTX(1)-A19C-SH was labeled using
      sulfhydryl-reactive Cy3-, Cy5-, and Alexa-dyes. Pharmacological characterization
      of fluorescently labeled HgTX(1)-A19C in radioligand binding studies indicated
      that these hongotoxin(1) analogues retain high-affinity for voltage-gated K+
      channels and a respective pharmacological profile. Cy3- and Alexa-dye-labeled
      hongotoxin(1) analogues were used to investigate the localization of K+ channels
      in brain sections. The distribution of toxin binding closely follows the
      distribution of K(v)1.2 immunoreactivity with the highest expression levels in
      the cerebellar Purkinje cell layer. Taken together, these results demonstrate
      that fluorescently labeled HgTX(1) analogues comprise novel probes to
      characterize a subset of voltage-gated K+ channels.

PMID- 12009930
TI  - Solid-phase synthesis of deglycobleomycins: a C-terminal tetraamine linker that
      permits direct evaluation of resin-bound bleomycins.
AB  - Deglycobleomycin analogues having different length polyamine side chains at the C
      terminus were synthesized using a novel solid-phase synthesis strategy that
      produces fully deprotected deglycobleomycin congeners attached to the resin.
      Detailed studies of DNA cleavage by these compounds and their resin-bound
      counterparts using supercoiled plasmid DNAs and DNA restriction fragments as
      substrates revealed that (i) the length of the polyamine side chain of free
      deglycoBLM had limited effect on its DNA cleavage potency or sequence
      selectivity, and (ii) the nature of the linker moiety between the resin and
      attached deglycobleomycin had a more substantial effect on the potency of DNA
      cleavage, but no effect on sequence selectivity of resin-bound deglycoBLMs. Resin
      bound 4 exhibited efficient DNA cleavage, indicating that its tetraamine linker
      moiety could be used for the elaboration and direct evaluation of bleomycin
      congeners attached to resins.

PMID- 12009931
TI  - Boron-containing folate receptor-targeted liposomes as potential delivery agents
      for neutron capture therapy.
AB  - Boron neutron capture therapy (BNCT) depends on the selective delivery of a
      sufficient number of (10)B atoms to tumor cells to sustain a lethal
      (10)B(n,alpha)(7)Li reaction. Expression of FR frequently is amplified among
      human tumors. The goal of the present study was to investigate folate receptor
      (FR)-targeted liposomes as potential carriers for a series of boron-containing
      agents. Two highly ionized boron compounds, Na(2)[B(12)H(11)SH] and Na(3)
      (B(20)H(17)NH(3)), were incorporated into liposomes by passive loading with
      encapsulation efficiencies of 6% and 15%, respectively. In addition, five weakly
      basic boronated polyamines were investigated. Two were the spermidine
      derivatives: N(5)-(4-carboranylbutyl)spermidine.3HCl (SPD-5), N(5)-[4-(2
      aminoethyl-o-carboranyl)butyl]spermidine.4HCl (ASPD-5). Three were the spermine
      derivatives: N(5)-(4-carboranylbutyl)spermine.4HCl (SPM-5), N(5)-[4-(2-aminoethyl
      o-carboranyl)butyl]spermine.5HCl (ASPM-5), and N(5),N(10)-bis(4
      carboranylbutyl)spermine.4 HCl (SPM-5,10). These were incorporated into liposomes
      by a pH-gradient-driven remote-loading method with varying loading efficiencies,
      which were influenced by the specific trapping agent and the structure of the
      boron compound. Greater loading efficiencies were obtained with lower molecular
      weight boron derivatives, using ammonium sulfate as the trapping agent, compared
      to those obtained with sodium citrate. The in vitro uptake of folate-derivatized,
      boronated liposomes was investigated using human KB squamous epithelial cancer
      cells, which have amplified FR expression. Higher cellular boron uptake (up to
      1584 microg per 10(9) cells) was observed with FR-targeted liposomes than with
      nontargeted control liposomes (up to 154 microg per 10(9) cells), irrespective of
      the chemical form of the boron and the method used for liposomal preparation. KB
      cell binding of the FR-targeted liposomes was saturable and could be blocked by 1
      mM free folic acid. Our findings suggest that further evaluation of FR-targeted
      liposomes is warranted to assess their potential as boron carriers for neutron
      capture therapy.

PMID- 12009932
TI  - Polyester dendritic systems for drug delivery applications: design, synthesis,
      and characterization.
AB  - Attachment of drugs to high molecular weight polymers can significantly improve
      both tumor targeting and therapeutic efficacy due to the enhanced permeability
      and retention effect observed in tumor tissue. However, the commercial
      availability of well-defined water-soluble polymeric systems with narrow
      polydispersities that are biocompatible, nontoxic, and nonimmunogenic is rather
      limited. To address this need, we have investigated dendritic polymers as
      promising scaffolds for the preparation of new soluble polymeric drug carriers
      due to their well-defined molecular architecture and their multiplicity of
      surface sites. Herein we show the design and synthesis of dendritic polyester
      systems based on the monomer unit 2,2-bis(hydroxymethyl)propanoic acid as a
      possible versatile drug carrier. The potent anticancer drug doxorubicin was
      attached via a pH-sensitive linkage to one of the carriers presented,
      demonstrating the feasibility of using these polyester dendritic structures to
      prepare a viable polymer-drug conjugate.

PMID- 12009933
TI  - Polyester dendritic systems for drug delivery applications: in vitro and in vivo
      evaluation.
AB  - High molecular weight polymers (> 20 000 Da) have been widely used as soluble
      drug carriers to improve drug targeting and therapeutic efficacy. Dendritic
      polymers are exceptional candidates for the preparation of near monodisperse drug
      carriers due to their well-defined structure, multivalency, and flexibility for
      tailored functionalization. We evaluated various dendritic architectures composed
      of a polyester dendritic scaffold based on the monomer unit 2,2
      bis(hydroxymethyl)propanoic acid for their suitability as drug carriers both in
      vitro and in vivo. These systems are both water soluble and nontoxic. In
      addition, the potent anticancer drug, doxorubicin, was covalently bound via a
      hydrazone linkage to a high molecular weight 3-arm poly(ethylene oxide)-dendrimer
      hybrid. Drug release was a function of pH, and the release rate was more rapid at
      pH < 6. The cytotoxicity of the DOX-polymer conjugate measured on multiple cancer
      lines in vitro was reduced but not eliminated, indicating that some active
      doxorubicin was released from the drug polymer conjugate under physiological
      conditions. Furthermore, biodistribution experiments show little accumulation of
      the DOX-polymer conjugate in vital organs, and the serum half-life of doxorubicin
      attached to an appropriate high molecular weight polymer has been significantly
      increased when compared to the free drug. Thus, this new macromolecular system
      exhibits promising characteristics for the development of new polymeric drug
      carriers.

PMID- 12009934
TI  - Molecular vehicles for targeted drug delivery.
AB  - Targeted drug delivery by cell-specific cytokines and antibodies promises greater
      drug efficacy and reduced side effects. We describe a novel strategy for assembly
      of drug delivery vehicles that does not require chemical modification of
      targeting proteins. The strategy relies on a noncovalent binding of standardized
      "payload" modules to targeting proteins expressed with a "docking" tag. The
      payload modules are constructed by linking drug carriers to an adapter protein
      capable of binding to a docking tag. Using fragments of bovine ribonuclease A as
      an adapter protein and a docking tag, we have constructed vascular endothelial
      growth factor (VEGF) based vehicles for gene delivery and for liposome delivery.
      Assembled vehicles displayed remarkable selectivity in drug delivery to cells
      overexpressing VEGF receptors. We expect that our strategy can be employed for
      targeted delivery of many therapeutic or imaging agents by different recombinant
      targeting proteins.

PMID- 12009935
TI  - Utility of thiol-cross-linked fluorescent dye labeled terminators for DNA
      sequencing.
AB  - Dipivaloyl-5-carboxyfluorescein N-hydroxysuccinimidyl ester 1 and 5
      propargylamino-2',3'-dideoxyuridine triphosphate 5 were modified with maleimide,
      haloacetamide, and sulfhydryl reactive functional groups to participate in cross
      conjugation reactions via sulfide bonds to generate fluorescently labeled,
      thioether cross-conjugated terminators 10 and 11. Their DNA sequencing potential
      was compared with an amide cross-conjugated terminator 13, synthesized by
      directly coupling 5-carboxyfluorescein NHS ester with 18-ddUTP 9. These
      terminators (10, 11, and 13) in combination with the Thermo Sequenase II DNA
      polymerase, in thermal cycle sequencing experiments, revealed that the thioether
      cross-conjugated terminator 10 and amide cross-conjugated terminator 13 served as
      good terminating substrates, generating satisfactory single-color gel images and
      electropherograms, while the other thioether cross-conjugated and maleimide
      derived one 11 underwent unexpected pH and temperature induced decomposition
      without showing fluorescent signatures for incorporation.

PMID- 12009936
TI  - Total chemical synthesis of a 27 kDa TASP protein derived from the MscL ion
      channel of M. tuberculosis by ketoxime-forming ligation.
AB  - A 27-kDa TASP protein, T(5)Msc(103-151), that was derived from the cytoplasmic
      domain (amino acid residues 103-151) of the MscL ion channel of M. tuberculosis
      was synthesized by ketoxime-forming chemoselective ligation between a template
      molecule carrying five pyruvic acid groups, and linear channel peptides carrying
      one aminooxyacetic acid group. Ketoxime-forming ligation provided for highly
      efficient assembly of this large totally synthetic protein construct with yields
      >90% with modest excess (1.5x) of the aminooxy peptide. Formation of the desired
      TASP molecule was confirmed by SDS-PAGE analysis and MALDI mass spectrometry. The
      effect of template attachment on the structure of the peptides constituting the
      TASP was assessed by circular dichroism spectroscopy. Attachment of the peptides
      to the topological template induces predominantly helical secondary structure,
      whereas an analogous peptide that did not bear an aminooxy group, MscL(103-151),
      does not exhibit significant secondary structure at pH 7 and is found to be
      monomeric in concentrations up to 65 microM. This observation can be explained by
      entropic destabilization of the unfolded state of T(5)Msc(103-151) due to the
      attachment to the template and the resulting loss of degrees of freedom. Pyruvic
      acid-based ketoxime-forming chemoselective ligation may thus prove to be a useful
      tool for the assembly of large, non-native protein constructs and their
      biophysical study.

PMID- 12009937
TI  - Efficient calf thymus DNA condensation upon binding with novel bile acid
      polyamine amides.
AB  - Polyamine amides have been prepared from lithocholic and cholic acids (5beta
      colanes) by acylation of tri-Boc-protected tetraamines spermine and thermine.
      These designed ligands for DNA are polyammonium ions at physiological pH. In NMR
      spectra, they display 14N-1H 1J = 51 Hz, 1:1:1 triplets, due to the symmetry of
      the R14NH(3)+ cations. The binding affinities of these conjugates for calf thymus
      DNA were determined using an ethidium bromide fluorescence quenching assay and
      compared with spermine and polylysine. DNA-binding affinities were dependent upon
      both salt concentration and the hydrophobicity or intermolecular bonding (facial
      effects) of the lipid moieties in these conjugates. Light scattering at 320 nm
      was used to determine DNA condensation and particle formation. The observed self
      assembly phenomena are discussed with respect to DNA charge neutralization and
      DNA bending with loss of ethidium cation intercalation sites, ultimately leading
      to DNA condensation. These polyamine amides are models for lipoplex formation
      with respect to gene delivery (lipofection), a key first step in gene therapy.

PMID- 12009938
TI  - Control of radioactivity pharmacokinetics of 99mTc-HYNIC-labeled polypeptides
      derivatized with ternary ligand complexes.
AB  - An enhancement of the target/nontarget ratio of radioactivity levels enables
      reliable diagnosis and therapy using polypeptide radiopharmaceuticals in nuclear
      medicine. In the present study, we investigated the effects of the
      physicochemical properties of radiometabolites on the radioactivity
      pharmacokinetics after administration of 99mTc-labeled polypeptides using 6
      hydrazinopyridine-3-carboxylic acid (HYNIC). Four ternary ligands (L) [3
      benzoylpyridine (BP), 3-acetylpyridine (AP), 3-nicotinic acid (NIC), pyridine
      (PY)] with different lipophilicity were selected as coligands for the preparation
      of 99mTc-HYNIC-polypeptides. Each of the ternary ligands tested provided 99mTc
      HYNIC-labeled galactosyl-neoalbumin (NGA) and Fab fragments of high stability
      with high radiochemical purity. Moreover, after administration of each 99mTc
      HYNIC-labeled NGA into normal mice, the respective ternary ligand [99mTc](HYNIC
      lysine)(tricine)(L) complexes were generated as final radiometabolites in the
      hepatic lysosome. The partition coefficients of [99mTc](HYNIC
      lysine)(tricine)(BP), [99mTc](HYNIC-lysine)(tricine)(AP), [99mTc](HYNIC
      lysine)(tricine)(NIC), and [99mTc](HYNIC-lysine)(tricine)(PY) were determined to
      be -2.21, -2.37, -2.93, and -2.73, respectively. Elimination rates of these
      radiometabolites from the lysosome were enhanced in the order of increasing
      lipophilicity of the radiometabolites. After injection of the four 99mTc-HYNIC
      labeled Fab fragments into normal mice, blood clearances of radioactivity were
      similar while radioactivity elimination rates from the kidney were enhanced in
      the order of increasing lipophilicity of the radiometabolites. The present study
      indicated that the lipophilicity of the radiometabolites constitutes one
      important factor affecting their elimination rates from the tissues. Thus, as
      ternary ligands facilitate alteration of the physicochemical properties of
      radiometabolites, the use of ternary ligand complexes might be applicable for
      controlling the pharmacokinetics of 99mTc-labeled polypeptides.

PMID- 12009939
TI  - Synthesis and biodistribution of 211At-labeled, biotinylated, and charge-modified
      poly-L-lysine: evaluation for use as an effector molecule in pretargeted
      intraperitoneal tumor therapy.
AB  - Poly-L-lysine (7, 21, and 204 kDa) has been evaluated as an effector carrier for
      use in pretargeted intraperitoneal tumor therapy. For the synthesis, the epsilon
      amino groups on the poly-L-lysine were modified in three steps utilizing
      conjugate biotinylation with biotin amidocaproate N-hydroxysuccinimide ester
      (BANHS), conjugate radiolabeling with (211)At using the intermediate reagent N
      succinimidyl 3-(trimethylstannyl)benzoate (m-MeATE), and charge modification
      using succinic anhydride, resulting in an increase in the molecular weight of
      approximately 80% of the final product. The labeling of the m-MeATE reagent and
      subsequent conjugation of the polymer were highly efficient with overall
      radiochemical yields in the range of 60-70%. The in vitro avidin binding ability
      of the modified polymer was almost complete (90-95%), as determined by binding to
      avidin beads using a convenient filter tube assay. Following intraperitoneal (ip)
      injection in athymic mice, the 13 kDa polymer product was cleared mainly via the
      kidneys with fast kinetics (biological half-live T(b) approximately 2 h) and with
      low whole-body retention. The clearance of the 38 kDa polymer was distributed
      between kidneys and liver, and the 363 kDa polymer was mainly sequestered by the
      liver with a T(b) of 8 h. Increased tissue uptake in the thyroid, lungs, stomach,
      and spleen following the distribution of the large effector molecules (38 and 363
      kDa) suggests that degradation of the polymers by the liver may release some of
      the label as free astatine/astatide.

PMID- 12009940
TI  - In vitro gene transfection using dendritic poly(L-lysine).
AB  - Monodispersed dendritic poly(L-lysine)s (DPKs) of several generations were
      synthesized, and their characteristics as a gene transfection reagent were then
      investigated. The agarose gel shift and ethidium bromide titration assay proved
      that the DPKs of the third generation and higher could form a complex with a
      plasmid DNA, and the degree of compaction of the DNA was increased by the
      increasing number of the generation. The DPKs of the fifth and sixth generation,
      which have 64 and 128 amine groups on the surface of the molecule, respectively,
      showed efficient gene transfection ability into several cultivated cell lines
      without significant cytotoxity. In addition, the transfection efficiency of the
      DPK of the sixth generation was not seriously reduced even if serum was added at
      50% of the final concentration into the transfection medium. Because we can
      strictly synthesize various DPK derivatives, which have several types of branch
      units, terminal cationic groups, and so on, they are expected to be a good object
      of study regarding the basic information on the detailed mechanism of gene
      transfection into cells. We also expect to be able to easily construct DPK-based
      functional gene carriers, e.g., DPKs modified by ligands such as a sugar chain,
      which can enable advanced gene delivery in vivo.

PMID- 12009941
TI  - Methotrexate conjugate with branched polypeptide influences Leishmania donovani
      infection in vitro and in experimental animals.
AB  - Methotrexate (MTX) has been coupled to various structurally related, polycationic
      (poly[Lys(DL-Ala(m))] (AK), poly[Lys(Ser(i)-DL-Ala(m))] (SAK), poly[Lys(DL-Ala(m)
      Leu(i))] (ALK)), or amphoteric (poly[Lys(Glu(i)-DL-Ala(m))] (EAK)) synthetic
      branched polypeptides containing poly[L-Lys] backbone by the aid of BOP reagent.
      The average degree of MTX incorporation was found to be dependent on the charge
      properties of the polymer. Under the experimental conditions used, the molar
      substitution ratio achieved was higher for polycations (25%) than for the
      amphoteric polypeptide (10%). We have studied the effect of polycationic
      polypeptides on Leishmania donovani infection. Results demonstrated that MTX
      conjugates in which the drug is covalently attached to carrier have pronounced
      leishmanicid activity. In this communication we showed that (a) a branched
      polypeptide-methotrexate conjugate with a polycationic carrier (ALK) increases
      the effect of MTX against Leishmania donovani infection in mice; (b) the covalent
      bond between the carrier and methotrexate is essential for both in vivo and in
      vitro activity; and (c) the number of Leishmania donovani parasites in infected
      macrophages are markedly reduced in conjugate treated animals. In vitro
      observation might also indicate that the MTX conjugate exhibits an effect through
      an uptake by macrophages which is different from that of the free drug.

PMID- 12009942
TI  - Synthesis of antisense oligonucleotide-peptide conjugate targeting to GLUT-1 in
      HepG-2 and MCF-7 Cells.
AB  - A simple procedure for the preparation of oligonucleotide-peptide conjugate was
      developed. p-Hydroxy-benzoic acid was used as a linker for the connection of the
      fragments of peptide and oligonucleotide. It was found that such formed linkage
      was stable under the conditions of conjugate synthesis. The designed conjugate
      targeting to GLUT-1 showed up to 50% inhibition of cell proliferation in HepG-2
      and MCF-7 cells. Comparing to the results from the expressed antisense RNA in
      cancer cells, it was proposed that the conjugate of signal peptide mimic and
      antisense oligonucleotide could improve the permeability of antisense
      oligonucleotide through cell membrane.

PMID- 12009943
TI  - NODAGATOC, a new chelator-coupled somatostatin analogue labeled with [67/68Ga]
      and [111In] for SPECT, PET, and targeted therapeutic applications of somatostatin
      receptor (hsst2) expressing tumors.
AB  - A monoreactive NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) derived
      prochelator (1-(1-carboxy-3-carbo-tert-butoxypropyl)-4,7-(carbo-tert
      butoxymethyl)-1,4,7-triazacyclononane (NODAGA(tBu)(3))) was synthesized in five
      steps with an overall yield of 21%. It is useful for the coupling to the N
      terminus of peptides on solid phase and in solution; it was coupled to [Tyr3]
      octreotide (TOC) on solid phase, and the resulting peptide, NODAGA-Tyr3
      octreotide (NODAGATOC), was labeled with the radiometals 111In and 67Ga in high
      yields and good specific activities. [67Ga]- and [111In]-NODAGA-Tyr3-octreotide
      appear to be useful to visualize primary tumors and metastases which express
      somatostatin receptors subtype 2 (sstr2), such as neuroendocrine tumors, because
      of their high affinity to this receptor subtype with IC(50) = 3.5 +/- 1.6 nM and
      1.7 +/- 0.2 nM, respectively. NODAGATOC could be used as a SPECT and PET tracer,
      when labeled with 111In, 67Ga, or 68Ga, and even for therapeutic applications.
      Surprisingly, [111In]-NODAGATOC shows 2 times higher binding affinity to sstr2,
      but also a factor of 4 higher affinity to sstr5 compared to [67Ga]-NODAGATOC.
      [67Ga]-NODAGATOC is very stable in serum and rat liver homogenate. There is no
      difference in the rate of internalization into AR4-2J rat pancreatic tumor cells;
      both radioligands are highly internalized, at 4 h a 3 times higher uptake
      compared to [111In]-DOTA-Tyr3-octreotide ([111In]-DOTATOC) was found. The
      biodistribution of [67Ga]-NODAGATOC in AR4-2J tumor bearing nude mice is very
      favorable at short times after injection; there is fast excretion from all
      nontarget organs except the kidneys and high uptake in sst receptor rich organs
      and in the AR4-2J tumor. Again it is superior to [111In]-DOTATOC in this respect.
      The results indicate an improved biological behavior which is likely due to the
      fact that an additional spacer group separates the chelate from the
      pharmacophoric part of the somatostatin analogue.

PMID- 12009944
TI  - Mixed-phase hybridization of short oligodeoxyribonucleotides on microscopic
      polymer particles: effect of one-base mismatches on duplex stability.
AB  - Hybridization of short oligonucleotides (10- and 11-mers) to complementary probes
      immobilized to microscopic polymer particles was quantified by a sandwich type
      mixed-phase hybridization assay based on a time-resolved fluorometric measurement
      of a photoluminescent europium(III) chelate from the surface of a single
      particle. Among the 54 sequences that were studied, 21 were fully complementary
      to the particle-bound probes, while 33 contained an internal one-base mismatch.
      The observed affinities were compared to those predicted by the nearest-neighbor
      model. In addition, various factors, such as the pore size of the particle, the
      linker structure, the charge type of the probe, and the efficiency of agitation,
      that might be expected to affect the kinetics of mixed-phase hybridization have
      been examined.

PMID- 12009945
TI  - Aliphatic ionenes as gene delivery agents: elucidation of structure-function
      relationship through modification of charge density and polymer length.
AB  - Polycation-based gene delivery agents are generally polydisperse populations
      whose properties are averaged among the different molecular weight species.
      Therefore, to understand the physicochemical properties of polycations and their
      relationships to cellular gene transfer, one needs to control the molecular
      weight of the polymer as well as its cationic charge density. To investigate the
      structure-function correlation of polycations with respect to the degree of
      polymerization (DP) and charge density, a series of model materials based on
      aliphatic ionenes was synthesized and fractionated into distinct molecular weight
      fractions with DP range from 14 to 32. The aliphatic ionene fractions and their
      polyelectrolyte complexes (PEC) with DNA were studied using physicochemical and
      biological methods. Ionene polymers were shown to possess low cytotoxicity
      (minimal viability of the P388D1 murine macrophage cells 80%). DP and charge
      density of the ionenes were shown to be the factors of effective control of PEC
      dissociation in water-salt solutions, with a diminished role of charge density
      upon lengthening the ionene chain. These polymer characteristics were also
      important for DNA-ionene PEC resistivity to DNase activity and the ability of
      ionenes to serve as gene delivery vectors in vitro and exhibited good correlation
      with the results of salt-induced dissociation of PEC. These data may be useful
      for developing correlations and mathematical models to predict synthetic gene
      delivery vector efficiency.

PMID- 12009946
TI  - Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes.
AB  - A number of quantitative three-dimensional tomographic near-infrared fluorescence
      imaging techniques have recently been developed and combined with MR imaging to
      yield highly detailed anatomic and molecular information in living organisms (1,
      2). Here we describe magnetic nanoparticle based MR contrast agents that have a
      near-infrared fluorescence (NIRF) that is activated by certain enzymes. The
      probes are prepared by conjugation of arginyl peptides to cross-linked iron oxide
      amine (amino-CLIO), either by a disulfide linkage or a thioether linker, followed
      by the attachment of the indocyanine dye Cy5.5. The NIRF of disulfide-linked
      conjugate was activated by DTT, while the NIRF of thioether-linked conjugate was
      activated by trypsin. Fluorescent quenching of the attached fluorochrome occurs
      in part due to the interaction with iron oxide, as evident by the activation of
      fluorescence with DTT when nanoparticles that have less than one dye attached per
      particle. With a SC injection of the probe, axillary and brachial lymph nodes
      were darkened on MR images and easily delineated by NIRF imaging. The probes may
      provide the basis for a new class of so-called smart nanoparticles, capable of
      pinpointing their position through their magnetic properties, while providing
      information on their environment by optical imaging techniques.

PMID- 12009947
TI  - In vitro and in vivo evaluation of a Technetium-99m-labeled cyclic RGD peptide as
      a specific marker of alpha(V)beta(3) integrin for tumor imaging.
AB  - Three amino acids residues, Arg-Gly-Asp (RGD), in vitronectin and fibronectin
      show affinity for alpha(V)beta(3) integrins expressed in vascular endothelial
      cells. That tumor growth can upregulate the expression of these integrins on
      tumor cells for invasion and metastasis and in tissue neovasculature suggests the
      potential of developing radiolabeled RGD peptides as antagonists of
      alpha(V)beta(3) integrins for broad spectrum tumor specific imaging. The
      polypeptide RGD-4C, which contains four cysteine residues for cyclization, has
      shown preferential localization on integrins at sites of tumor angiogenesis. Both
      RGD-4C and RGE (Arg-Gly-Glu)-4C (as control) were purchased and conjugated with 6
      hydrazinopyridine-3-carboxylic acid (HYNIC) for 99mTc radiolabeling. After
      purification of the conjugated peptides by a C18 Sep-Pak cartridge with 20%
      methanol, both peptides were radiolabeled using tricine. For cell binding
      studies, both 99mTc peptides were further purified by SE HPLC. High specific
      radioactivity of labeled cyclized RGD/E (cyclized RGD/E will be simplified as
      RGD/E through out the text) of about 20 Ci/micromol was achieved. Both 99mTc
      complexes were stable in the labeling solution for over 24 h at room temperature.
      In the human umbilical vein endothelial (HUVE) cell studies, the binding at 1 h
      of radiolabeled RGD/E was determined at 4 degrees C and at concentrations in the
      picomolar to nanomolar range. Under these conditions, cell accumulation of 99mTc
      in the case of RGD was as much as 16 times greater than the control RGE. As a
      check on specificity, 7 nM of native cyclized RGD blocked 50% of the binding of
      99mTc-labeled RGD to cells. The binding percentage of 99mTc-labeled RGD to
      purified alpha(V)beta(3) integrin protein, as determined by SE HPLC, increased
      with the concentration of the integrin while 99mTc-labeled RGE showed no binding.
      The association constant for 99mTc-RGD was modest at 7 x 10(6) M(-)(1). In both
      human renal adenocarcinoma (ACHN) and human colon cancer cell line (LS174T) nude
      mouse tumor models, the accumulation of 99mTc-labeled RGD/E exhibited no
      statistical difference. In conclusion, possibly because of limited numbers of
      alpha(V)beta(3) integrin receptors per tumor cell and low binding affinity,
      radiolabeled RGD peptides may have limitations as tumor imaging agents.

PMID- 12009948
TI  - Evaluation of different alpha-Galactosyl glycoconjugates for use in
      xenotransplantation.
AB  - Porcine organs are rapidly rejected after transplantation into primate recipients
      due to the presence of preexisting immunoglobulins that bind to terminal
      galactose alpha1,3 galactose residues (alpha-galactosyl) present on porcine
      glycoproteins and glycolipids. Currently available immunosuppressive reagents
      have been largely ineffective at controlling the synthesis of these anti-Gal
      antibodies. Nonantigenic hapten polymers have been shown to be effective
      materials for blocking humoral immune responses in various model systems. We have
      developed a series of alpha-galactosyl glycoconjugate polymers and tested their
      ability to block anti-Gal antibody binding in vitro and in vivo. A galactose
      alpha1,3 galactose beta 1,4 GlcNAc trisaccharide free acid (TRFA) with a hexanoic
      acid spacer, containing five methylene groups and a carboxylic acid, was produced
      and coupled to a variety of polymeric backbones including dextran, branched
      poly(ethylene glycol) (PEG), and poly-L-lysine. The ability of monomeric TRFA and
      the alpha-galactosyl conjugates to block anti-Gal IgG and IgM binding was
      determined using a competition ELISA assay on defined HSA-Gal glycoconjugates and
      porcine microvascular endothelial cell substrates. We show that branched PEG
      carriers, with a TRFA sugar attached to each branch, exhibit enhanced antibody
      blocking ability compared to TRFA, but at higher target antigen densities these
      simple PEG conjugates are no more effective then an equivalent amount of TRFA in
      blocking anti-Gal IgM antibody interactions. In contrast, polymers of the
      branched PEG conjugates and linear conjugates made using dextran and poly-L
      lysine were 2000 to 70000-fold more effective inhibitors of anti-Gal antibodies.
      In a study using nonhuman primates, a single dose infusion of polymeric PEG or
      dextran glycoconjugates dramatically reduced the level of circulating anti-Gal
      antibodies in cynomologus monkeys for at least 72 h. Glycoconjugates similar to
      these might be useful both to block anti-Gal interactions in vivo and to
      specifically control the induced anti-Gal immune response.

PMID- 12009949
TI  - Inhibitory effect of supramolecular polyrotaxane-dipeptide conjugates on digested
      peptide uptake via intestinal human peptide transporter.
AB  - The effect of polyrotaxane-dipeptide (Val-Lys) conjugates on the uptake of a
      model dipeptide (Gly-Sar) was examined via human peptide transporter (hPEPT1) on
      HeLa cells. Here, Val-Lys groups are introduced to alpha-CDs, which are threaded
      onto a poly(ethylene oxide) chain capped with bulky end-groups (polyrotaxane).
      The Gly-Sar uptake via hPEPT1 was significantly inhibited in the polyrotaxane
      conjugates, and this inhibitory effect was not explained by the sum of
      interaction between hPEPT1 and alpha-CD-Val-Lys conjugates. Further, the
      inhibition was significantly greater than those observed in dextran-Val-Lys
      conjugates. Therefore, our data clearly suggests that supramolecular structure in
      the polyrotaxane conjugates contributes considerably to the inhibitory effect via
      multivalent binding of Val-Lys groups with hPEPT1.

PMID- 12009950
TI  - A streptavidin-biotin binding system that minimizes blocking by endogenous
      biotin.
AB  - Pretargeted radioimmunotherapy specifically targets radiation to tumors using
      antibody-streptavidin conjugates followed by radiolabeled biotin. A potential
      barrier to this cancer therapy is the presence of endogenous biotin in serum,
      which can block the biotin-binding sites of the antibody-streptavidin conjugate
      before the administration of radiolabeled biotin. Serum-derived biotin can also
      be problematic in clinical diagnostic applications. Due to the extremely slow
      dissociation of the biotin-streptavidin complex, this endogenous biotin can
      irreversibly block the biotin-binding sites of streptavidin and reduce
      therapeutic efficacy, as well as reduce sensitivity in diagnostic assays. We
      tested a streptavidin mutant (SAv-Y43A), which has a 67-fold lower affinity for
      biotin than wild type streptavidin, and three bivalent bis-biotin constructs as
      replacements for wild-type streptavidin and biotin used in pretargeting and
      clinical diagnostics. Biotin dimers were engineered with certain parameters
      including water solubility, biotinidase resistance, and linker lengths long
      enough to span the distance between two biotin-binding sites of streptavidin. The
      bivalent biotins were compared to biotin in exchange, retention, and off-rate
      assays. The faster off-rate of SAv-Y43A allowed efficient exchange of prebound
      biotin by the biotin dimers. In fluorescent competition experiments, the biotin
      dimer ligands displayed high avidity binding and essentially irreversible
      retention with SAv-Y43A. The off-rate of a biotinidase-stabilized biotin dimer
      from SAv-Y43A was 4.36 x 10(-)(6) s(-)(1), over 640 times slower compared to
      biotin. These findings strongly suggest that employing a mutant streptavidin in
      concert with a bivalent biotin can mitigate the deleterious impact of endogenous
      biotin, by allowing exchange of bound biotin and retention of the biotin dimer
      carriers.

PMID- 12009951
TI  - A 99mTc(I)-postlabeled high affinity bombesin analogue as a potential tumor
      imaging agent.
AB  - The overexpression of neuropeptide receptors observed in many cancers provides an
      attractive target for tumor imaging and therapy. Bombesin is a peptide exhibiting
      a high affinity for the gastrin releasing peptide (GRP) receptor, which is
      overexpressed by a variety of tumors such as breast or prostate cancer. In the
      present study, we have evaluated if the bombesin analogue [N(alpha)-histidinyl
      acetate]bombesin(7-14), radiolabeled with the novel [99mTc(OH(2))(3)(CO)(3)]+,
      has the potential to be used as a diagnostic radiopharmaceutical. Receptor
      saturation studies, carried out on the GRP receptor-expressing PC-3 human
      prostate cancer cell line, revealed for [99mTc(CO)(3)-N(alpha)-histidinyl
      acetate]bombesin(7-14) K(d) values in the subnanomolar range. Competitive binding
      assays, using the cold rhenium(I)-labeled analogue as a surrogate for the 99mTc
      conjugate, also showed high affinity binding. Incubation of the radioconjugate
      with PC-3 cells resulted in a rapid temperature- and time-dependent specific
      internalization. At 37 degrees C more than 70% was internalized within the first
      15 min and remained constant up to 2 h. Despite the weak proteolytic stability of
      [99mTc(CO)(3)-N(alpha)-histidinyl acetate]bombesin(7-14) in vitro,
      biodistribution studies, performed in PC-3 tumor-bearing mice, showed low uptake
      in the tumor (0.89 +/- 0.27% ID/g 30 min pi) but high uptake into the pancreas
      (7.11 +/- 3.93% ID/g 30 min pi), a GRP receptor-positive organ. Blockade
      experiment (coinjection of 300 microg bombesin/mouse with the radioligand) showed
      specificity of the uptake. Despite the low tumor uptake, tumor-to-blood ratios of
      2.0 and 2.7 and tumor-to-muscle ratios of 8.9 and 8.0 were obtained at 30 min and
      1.5 h postinjection, respectively. The promising results merit the future in vivo
      investigation of 99mTc/188Re-tricarbonyl-labeled bombesin analogues.

PMID- 12009952
TI  - Novel near-infrared cyanine fluorochromes: synthesis, properties, and
      bioconjugation.
AB  - Recently, near-infrared (NIR) fluorescence light has been applied to image
      various biological events in vivo, because it penetrates tissue more efficiently
      than light in the visible spectrum. Compounds exhibiting fluorescent properties
      in the NIR range are key elements for this upcoming optical imaging technology.
      In this paper, we report the synthesis of four new, water-soluble NIR cyanine
      fluorochromes which have superior chemical stability and optical properties. Each
      fluorochrome was designed with a monoreactive carboxyl group for labeling
      purposes. When multiple fluorochromes were attached to a single macromolecule,
      fluorescence quenching was observed. On the basis of this property, a novel
      autoquenched enzyme sensitive NIR fluorescence probe was prepared.

PMID- 12009953
TI  - Streptavidin in antibody pretargeting. 3. Comparison of biotin binding and tissue
      localization of 1,2-cyclohexanedione and succinic anhydride modified recombinant
      streptavidin.
AB  - Recombinant streptavidin (rSAv) is of interest as a carrier of alpha-emitting
      radionuclides in pretargeting protocols for cancer therapy. Due to the inherently
      high kidney localization of rSAv, modification of this protein is required before
      it can be useful in pretargeting. Previous studies (Wilbur, D. S., Hamlin, D. K.
      et al. (1998) Bioconjugate Chem. 9, 322-330) have shown that succinylation of
      rSAv using succinic anhydride decreases the kidney localization appreciably. In
      continuing studies, the biotin binding characteristics and biodistribution in
      mice of rSAv modified by reaction with succinic anhydride (amine modification) or
      1,2-cyclohexanedione (arginine modification) have been compared. Modification of
      rSAv was conducted using 5-50 mol equiv of succinic anhydride and 60-200 mol
      equiv of 1,2-cyclohexanedione. Most studies were conducted using rSAv modified
      with the highest quantities of reagents. Succinylation of rSAv did not alter
      binding with biotin derivatives, but a small increase in the biotin derivative
      dissociation rate was noted for arginine-modified rSAv. Amino acid analysis of
      1,2-cyclohexanedione-treated rSAv indicated about 40% of the arginine residues,
      or an average of 1.6 residues per subunit, were modified, whereas none of the
      lysine residues were modified. IEF analyses showed that the pI of the arginine
      modified rSAv was 5.3-6, whereas the pI for the succinylated rSAv was
      approximately 4. Electrospray mass spectral analyses indicated that one to three
      conjugates of 1,2-cyclohexanedione, and two to three conjugates of succinic
      anhydride, were obtained per subunit. Both modification reactions resulted in
      greatly decreasing the kidney localization of rSAv (normally 20-25% ID/g at 4,
      24, and 48 h pi). However, the kidney concentration for the succinylated rSAv
      continued to decrease (5% ID/g to 1.5% ID/g) from 4 to 48 h pi, whereas the
      concentration (5% ID/g) remained constant over that period of time for the
      arginine-modified rSAv. In contrast to this, the liver concentration appeared to
      be slightly higher (3% ID/g vs 2% ID/g) at the later time points for the
      succinylated rSAv. When less than 50 mol equiv of succinic anhydride were
      employed in the modification of rSAv, a correlation between increasing kidney
      localization with decreasing equivalents reacted was observed. Although the
      differences in the two modified rSAv are not substantial, succinylated rSAv
      appears to have more favorable properties for pretargeting studies.

PMID- 12009954
TI  - Surface-tethered DNA complexes for enhanced gene delivery.
AB  - Overcoming the barriers to efficient gene transfer is a fundamental goal of
      biotechnology. A versatile approach to enhance the delivery of nonviral DNA
      involves complexation with cationic polymers, which can be designed to overcome
      the barriers to effective gene transfer. More recently, DNA release from a
      polymer substrate or scaffold has been shown to enhance gene transfer, likely by
      increasing DNA concentrations in the cell microenvironment. We propose a novel
      approach that combines these two strategies in which cationic polymer/DNA
      complexes are tethered to a substrate that supports cell adhesion. The cationic
      polymers package the DNA for efficient internalization and the surface tethering
      functions to maintain elevated concentrations in the cell microenvironment for
      cells adhered to the substrate. The cationic polymer polylysine (degree of
      polymerization equal to 19 or 150) was modified with biotin groups, which was
      confirmed by mass spectrometry and biochemical analysis. Complex formation of DNA
      with biotinylated-polylysine, or mixtures of biotinylated and nonbiotinylated
      polylysines, was confirmed by gel electrophoresis. Plasmid DNA encoding for the
      reporter gene beta-galactosidase was complexed with different mixtures of
      biotinylated and nonbiotinylated polylysine and incubated on neutravidin
      (nonglycosylated avidin)-coated surfaces. DNA surface densities ranging from 0.1
      to 4.3 microg/cm2 were observed and found to be a function of the number of
      biotin groups, the molecular weight of the polylysine, and the amount of DNA.
      HEK293T or NIH/3T3 cells were then seeded onto the DNA-modified surfaces, and
      transfection was quantified at 48 and 96 h. Transfection by the DNA surfaces was
      observed with both cell lines, and expression levels up to 100 fold greater than
      bulk delivery of the complexes was obtained. Transfection was found to be a
      function of the surface DNA quantities and the number of tethers on the complex.
      Transfected cells were observed only in the region in which DNA complexes were
      tethered, suggesting that the location of transfected cells can be specifically
      controlled. Surface tethering of DNA represents a promising approach to enhancing
      gene transfer and spatially controlling gene delivery, which may have
      applications to a multitude of fields ranging from tissue engineering to
      functional genomics.

PMID- 12009955
TI  - Development of a nonviral gene delivery vehicle for systemic application.
AB  - Polycation vehicles used for in vitro gene delivery require alteration for
      successful application in vivo. Modification of polycations by direct grafting of
      additional components, e.g., poly(ethylene glycol) (PEG), either before or after
      DNA complexation, tend to interfere with polymer/DNA binding interactions; this
      is a particular problem for short polycations such as linear, beta-cyclodextrin
      containing polycations (betaCDPs). Here, a new method of betaCDP polyplex
      (polycation/DNA composite structures) modification is presented that exploits the
      ability to form inclusion complexes between cyclodextrins and adamantane. Surface
      PEGylated betaCDP polyplexes are formed by self-assembly of the polyplexes with
      adamantane-PEG conjugates. While unmodified polyplexes rapidly aggregate and
      precipitate in salt solutions, the PEGylated betaCDP polyplexes are stable at
      conditions of physiological salt concentration. Addition of targeting ligands to
      the adamantane-PEG conjugates allows for receptor-mediated delivery;
      galactosylated betaCDP-based particles reveal selective targeting to hepatocytes
      via the asialoglycoprotein receptor. Galactosylated particles transfect hepatoma
      cells with 10-fold higher efficiency than glucosylated particles (control), but
      show no preferential transfection in a cell line lacking the asialoglycoprotein
      receptor. Thus, surface modification of betaCDP-based polyplexes through the use
      of cyclodextrin/adamantane host/guest interactions endows the particles with
      properties appropriate for systemic application.

PMID- 12009956
TI  - Formation of fibrinogen-based hydrogels using phototriggerable diplasmalogen
      liposomes.
AB  - We report the triggered release of Ca2+ from liposomal compartments to induce
      rapid gelation of protein-based hydrogels. Phototriggerable liposomes were
      designed by entrapping CaCl(2) within liposomes composed of 38:57:5
      diplasmenylcholine (DPPlsC):disteroylphosphatidylcholine
      (DSPC):bacteriochlorophyll (Bchl). These liposomes release >80% of their
      entrapped Ca2+ within 15 min when irradiated at 800 nm (800 mW/cm2). A precursor
      solution, containing liposomes suspended in aqueous human fibrinogen and
      transglutaminase (TGase), remained fluid for several hours in the dark, but
      gelled rapidly when exposed to 800 nm excitation, as a result of photosensitized
      Ca2+ release and TG-induced fibrinogen cross-linking. TGase and hrFXIII
      activities, determined using a fluorimetric dansylcadaverine assay, were found to
      depend strongly on irradiation time and reaction temperature. SDS-PAGE of the
      photolyzed reaction mixture revealed that gelation arises from enzyme-catalyzed
      cross-linking of predominately the alpha and gamma chains of fibrinogen. This
      approach to the phototriggered formation of protein hydrogels creates new
      opportunities for biomaterials applications in drug delivery, tissue engineering,
      and wound healing.

PMID- 12009957
TI  - Dendrimers as carrier protein mimetics for IgE antibody recognition. Synthesis
      and characterization of densely penicilloylated dendrimers.
AB  - The synthesis of benzylpenicilloyl-containing dendrimers has been achieved by a
      convenient procedure involving quantitative functionalization of the terminal
      amino groups of the three Starbust PAMAM generations used (G(n); n = 0, 1, 2).
      All these densely penicilloylated dendrimers (G(n)P) exhibit similar, simple NMR
      spectroscopic data suggesting highly symmetric structures and a monodisperse
      nature, and the results obtained from MALDI-TOF-MS demonstrate their exact
      chemical composition. The use of PAMAM dendrimers has allowed us to synthesize,
      for the first time, carrier benzylpenicilloyl conjugates (G(n)P) of precisely
      defined chemical structure. The attempts to synthesize G(2)P show that forced
      experimental conditions are not always useful for the functionalization of the
      dendrimer, especially in introducing bulky groups. The initial results with sera
      from patients with different RAST levels were positive and thus suggestive that
      inhibition occurs, so recognition exists; we can therefore conclude that the
      hapten-carrier (dendrimer) conjugates studied mimic recognition with natural
      hapten-carrier (protein) conjugates.

PMID- 12009958
TI  - Improved tumor selectivity of radiolabeled peptides by receptor and antigen dual
      targeting in the neurotensin receptor model.
AB  - Radiolabeled peptides are emerging tools for diagnosis and therapy of tumors
      overexpressing receptors. However, binding to receptors expressed by nontumor
      tissues may cause toxicity. The objective of this study was to specifically
      enhance the binding affinity of labeled peptides to tumor cells, as opposed to
      receptor-positive nontumor cells, to ensure targeting selectivity. This was
      achieved by the simultaneous binding of hapten-bearing peptides to their receptor
      and to a tumor-associated antigen, mediated by a bispecific antibody directed to
      the tumor antigen and to the hapten. Binding of labeled neurotensin analogues
      bearing the DTPA(indium) hapten (NT-DTPA(111In)) to human colorectal carcinoma
      cells (HT29), which express the neurotensin receptor (NTR1) and carcinoembryonic
      antigen (CEA), was studied in the presence of a bispecific antibody (BsmAb)
      directed to CEA and to DTPA(indium). In vitro dual binding of NT-DTPA in the
      presence of BsmAb was about 6.5-fold higher than monovalent binding to NTR1 and
      3.5-fold higher than the sum of the monovalent bindings to NTR1 or to CEA,
      suggesting cooperativity. Increased binding under bivalent conditions translated
      into increased internalization. In vivo pretargeting with BsmAb enhanced tumor
      uptake and tumor retention. Hapten bearing peptides binding simultaneously an
      overexpressed cell-surface receptor and a tumor antigen show increased
      selectivity to target tumor cells as compared to cells only expressing the cell
      surface receptor. Better resistance to enzymatic degradation and optimized
      administration protocols should further enhance in vivo targeting selectivity and
      may allow the development of radiopharmaceuticals labeled with isotopes suitable
      for radiotherapy such as 131I or 90Y.

PMID- 12009959
TI  - Profiling solid-phase synthesis products by free-solution conjugate capillary
      electrophoresis.
AB  - Solid-phase synthesis of oligomers, both natural and nonnatural, has proved to be
      invaluable for the development of many areas of biotechnology. A critical step in
      the solid-phase synthesis of any oligomer is determining the number and
      concentration of different constituents present in the product mixture resulting
      from the synthesis, both before and after purification. Most typically, this
      analysis is performed by reversed-phase high performance liquid chromatography
      (RP-HPLC), with the separated components detected by UV absorbance. Recently, we
      described a novel technique, free-solution conjugate electrophoresis (FSCE), for
      the high-resolution separation and sensitive laser-induced fluorescence (LIF)
      detection of uncharged, synthetic polymers, PEG in particular. In this report, we
      apply this bioconjugate capillary electrophoresis technique to analyze products
      of the solid-phase synthesis of oligomeric polyamides, namely poly(N-substituted
      glycines), or polypeptoids. When compared to more traditional RP-HPLC analysis,
      FSCE analysis of oligomeric peptoids results in separation resolutions that are
      approximately five times higher and separation efficiencies that are increased by
      150%. Moreover, when FSCE with LIF detection is applied to the analysis of
      oligomeric polyamides after HPLC purification, impurities that are not detectable
      in RP-HPLC analysis are readily separated and detected. With the advent of
      capillary array electrophoresis (CAE), which allows for automated, parallel
      analysis of many different samples, we believe that FSCE will be especially
      applicable to the analysis of combinatorial synthesis products, by allowing
      researchers to evaluate many different samples in a single, highly parallel,
      fully automated analysis. This is in contrast to RP-HPLC analysis, in which
      samples must be analyzed in series.

PMID- 12009960
TI  - Synthesis and properties of novel tetraalkyl cationic lipids.
AB  - The synthesis, physical properties, and transfection potencies of two
      representives of a new class of divalent, tetraalkyl cationic lipids is
      described. These cationic lipids are dimers of N,N-Dioleyl-N,N-dimethylammonium
      chloride (DODAC) joined by a hydrocarbon tether three or six carbons in length
      (TODMAC3 and TODMAC6, respectively). It is shown that TODMAC6 can display
      improved transfection properties in comparison to DODAC when formulated into
      plasmid DNA-cationic lipid complexes. These improved transfection potencies are
      observed at cationic lipid to DNA charge ratios of two or higher. It is also
      shown that TODMAC6 exhibits equivalent or improved ability (as compared to DODAC)
      to induce nonbilayer structure in mixtures with anionic lipid. This is consistent
      with the hypothesis that the ability of cationic lipids to induce nonbilayer
      structures when mixed with anionic lipids is correlated to their transfection
      potency. Complexes containing TODMAC3 on the other hand exhibit lower
      transfection potencies than achieved with DODAC, behavior that is consistent with
      steric effects limiting the formation of ion pairs with anionic lipids. It is
      concluded that TODMAC6 exhibits potential as a transfection agent for in vitro
      and in vivo use and that the design of cationic lipids according to their ability
      to induce nonbilayer structure provides a useful guide for synthesis of new
      cationic lipids.

PMID- 12009961
TI  - New Fmoc pseudoisocytosine monomer for the synthesis of a bis-PNA molecule by
      automated solid-phase Fmoc chemistry.
AB  - The synthesis of N-[2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-(2-N
      (benzyloxycarbonyl)isocytosin-5-ylacetyl)glycine monomer and its incorporation
      into a PNA molecule via automated Fmoc solid-phase chemistry is described.

PMID- 12009962
TI  - A simple two-step approach for introducing a protected diaminedithiol chelator
      during solid-phase assembly of peptides.
AB  - A simple synthetic strategy is described to incorporate a protected
      diaminedithiol (N(2)S(2)) chelator during Fmoc solid-phase synthesis of short
      peptides. The resulting constructs could be efficiently labeled with technetium
      99m (99mTc). The chelator was assembled at the N-terminus of peptides in a two
      step procedure where the deprotected terminal amino group was first reacted with
      di-Fmoc-diaminopropionic acid (Fmoc-DAP-[Fmoc]-OH). The two protected amino
      groups were then simultaneously deprotected and subsequently reacted with S
      benzoylthiolglycolic acid (TGA) to generate a protected N(2)S(2) chelator. This
      metal binding site was introduced into di- and tripeptides. Each peptide
      construct was composed of a C-terminal lysine residue and an N-terminal
      diaminopropionic moiety modified to create the chelator site. The epsilon-amino
      group at the C-terminal lysine was further derivatized with a nitroimidazole
      group to facilitate cellular retention. The resulting constructs were then
      cleaved from the resin support, purified, and labeled with [99mTc]pertechnetate.
      Six constructs were prepared differing by a single amino acid inserted between
      the diaminopropionic acid and lysine residues. Optimal labeling yields of >70%
      were achieved around neutral pH and heating at 75 degrees C for 10 min. Purified
      99mTc-labeled constructs were found to accumulate in Chinese hamster ovary (CHO)
      cells in vitro as a function of charge and hydrophobicity.

PMID- 12009963
TI  - Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate
      conjugates.
AB  - Folate conjugates (PNIPAM-NH-FA) of a copolymer of N-isopropylacrylamide (NIPAM)
      and amino-N'-ethylenedioxy-bis(ethylacrylamide) were prepared by an efficient
      synthesis leading to random grafting, via a short dioxyethylene spacer, of
      approximately 7 folic acid residues per macromolecule. The chemical composition
      of the copolymer was characterized by (1)H NMR and UV/vis spectroscopy. A
      fluorophore-labeled folate PNIPAM conjugate was tested by in vitro assays
      performed with cultured KB-31 cells overexpressing the folate receptor. The
      cellular uptake of the copolymer was found to be temperature dependent and was
      competitively decreased by free folic acid, indicating that the polymer uptake is
      mediated specifically by the folate receptor. Hydrophobically modified folate
      conjugates of NIPAM, amino-N'-ethylenedioxy-bis(ethylacrylamide) copolymers,
      bearing a small number of n-octadecyl groups were prepared following a modified
      synthetic procedure for use in future studies of FA-targeted liposomes.

PMID- 12009964
TI  - Transition metal-carbonyl labeling of biotin and avidin for use in solid-phase
      carbonyl metallo immunoassay (CMIA).
AB  - The preparation of several transition metal-carbonyl tracers of biotin and avidin
      is described. Multiple labeling of avidin was achieved by acylation of some of
      its amine-bearing residues with N-succinimidyl 4-pentynoate (dicobalt
      hexacarbonyl). By varying the initial amount of this complex, protein conjugates
      with the extent of derivatization of up to 13 were obtained. Biotin was labeled
      with one (eta5-cyclopentadienyl)manganese tricarbonyl moiety by reaction of
      biotin hydrazide, whereas multiple labeling was reached by successive conjugation
      of biotin and N-succinimidyl 4-pentynoate (dicobalt hexacarbonyl) or (eta5
      cyclopentadienyl)iron dicarbonyl (eta1-N-maleimidato) to poly-L-lysine or fourth
      generation Starburst dendrimer. All the conjugates displayed a good to excellent
      bioaffinity toward their respective counterparts, as measured by competitive
      enzymatic assays.

PMID- 12009965
TI  - Rapid analysis of methanol in grape-derived distillation products using near
      infrared transmission spectroscopy.
AB  - Samples of distillates derived from the production of wine-fortifying spirit were
      analyzed for methanol by gas chromatography (GC) and near-infrared spectroscopy
      (NIRS). NIRS calibration models were developed which could accurately predict
      methanol concentrations in samples of fortifying spirit that had been produced
      over a period of three years from four different commercial distillation
      facilities. The best accuracy of the predictive models, as measured by the
      standard error of prediction value, was 0.06 g/L methanol. Other distillation
      fractions, produced during preparation of commercial fortifying spirit, were also
      examined. The most useful NIRS calibration models used partial least squares
      regression on continuous spectra from a scanning instrument, but it was
      demonstrated that calibrations could also be developed with a smaller number of
      fixed wavelengths, using multiple linear regression models. NIRS offers the
      advantages of rapid analysis, with simple routine operation, and may offer the
      potential for in-line process control in the operation of a commercial
      distillation facility.

PMID- 12009966
TI  - Fractal analysis of ice crystals in frozen food.
AB  - Fractal analysis of the morphology of ice crystal particles in frozen food was
      attempted for frozen soybean curd (tofu). From a microscopic image analysis of
      the ice crystal particles, it was found that the perimeter of the ice crystal
      particles could be recognized as a fractal. Effects of the storage time and
      storage temperature on the fractal dimension (d(p)) of the perimeter of the ice
      crystal particles were also investigated. As storage time was increased, the d(p)
      value tended to decrease. When the storage temperature was increased, the value
      of d(p) decreased more rapidly. The changes corresponded to the visual
      observation of the shape change for the ice crystal particles during storage
      reported by many researchers, suggesting that the fractal dimension d(p) could be
      used as a quantitative indicator reflecting the surface roughness of ice crystal
      particles.

PMID- 12009967
TI  - Derivative potentiometric stripping analysis (dPSA) used for the determination of
      cadmium, copper, lead, and zinc in Sicilian olive oils.
AB  - Derivative potentiometric stripping analysis (dPSA) was utilized to evaluate the
      Cd(II), Cu(II), Pb(II), and Zn(II) content in olive oil samples produced in
      Sicily in the crop year 2000-2001. The repeatability of the method was attested
      at 86.36% for cadmium, at 94.94% for copper, at 99.00% for lead, and at 98.92%
      for zinc. Recovery tests were carried out, both on cleanup procedures and on
      extraction steps, on olive oil spiked at different levels; obtained recoveries
      were 84.52 +/- 9.86 for cadmium, 97.34 +/- 2.72 for copper, 100.68 +/- 0.67 for
      lead and 83.35 +/- 1.72 for zinc. Theoretic detection limits were 1.2 ng g(-1)
      for Cd, 3.6 ng g(-1) for Cu, 5.9 ng g(-1) for Pb, and 14.3 ng g(-1) for Zn. Found
      concentrations range were 15.94-58.51 ng g(-1) for Cu, 32.64-156.48 ng g(-1) for
      Pb, and 157.00-385.22 ng g(-1) for Zn. Copper, lead, and zinc were found in all
      samples. The main advantage of this determination consists of a not too
      aggressive metals extraction procedure using hydrochloric acid, which avoids
      losses of elements typical of sample calcinations methods.

PMID- 12009968
TI  - Novel method for detecting bovine immunoglobulin G in dried porcine plasma as an
      indicator of bovine plasma contamination.
AB  - Current U.S. Food and Drug Administration regulations prohibit feeding of protein
      derived from mammalian tissue, excluding blood and blood products and any product
      that consists entirely of porcine or equine protein. A novel lateral flow
      immunoassay device has been developed that can quickly and qualitatively
      determine the presence of bovine immunoglobulin G (IgG), a major component in
      blood products, at very low levels (0.01% v/v). The device can be used to test
      for bovine IgG commingling in spray-dried porcine plasma used in the feed
      industry. Producers and consumers alike could use this device to verify product
      content at threshold levels.

PMID- 12009969
TI  - Application of (1)h NMR and multivariate statistics for screening complex
      mixtures: quality control and authenticity of instant coffee.
AB  - Principal components analysis (PCA) followed by linear discriminant analysis
      (LDA) of the nuclear magnetic resonance (NMR) spectra from 98 instant spray-dried
      coffees, obtained from 3 different producers, correctly attributed 99% of the
      samples to their manufacturer. Blind testing of the PCA model with a further 36
      samples of instant coffee resulted in a 100% success rate in identifying the
      samples from the 3 manufacturers. Coffees from one manufacturer were also
      assigned into 2 groups using these techniques, and the compound 5-(hydroxymethyl)
      2-furaldehyde was identified as the primary marker of differentiation.

PMID- 12009970
TI  - Application of FTIR spectroscopy for the quantification of sugars in mango juice
      as a function of ripening.
AB  - FTIR-ATR spectroscopy and multivariate analysis were used for quantification of
      sugars in mango juices as a function of ripening. Calibration was based on
      sucrose/glucose/fructose mixtures, with six concentration levels and following a
      triangular experimental design. PLS1 regression of the spectra first derivatives
      gave the best results, enabling quantification of fructose, sucrose, and glucose
      with 1.4, 1.4, and 4.9% prediction errors, respectively. Throughout ripening,
      sucrose and fructose were accurately quantified by PLS-FTIR, whereas the accuracy
      of glucose determination decreased at later stages, when concentrations fell to
      0.6-1.5 g/L. These results enabled a correlation with fruit ripening stage to be
      established. This may be particularly useful to detect over-ripening in fresh
      fruits, a period when other indicators (pH and % soluble solids (SS)) do not
      change significantly; this knowledge may help in predicting fruit stability to
      transport and storage. Similar information obtained for nonfresh juices (in which
      pH and %SS may be masked by additives), may help determine whether the source
      fruits had suitable ripening stages.

PMID- 12009971
TI  - Determination of antioxidant power of red and white wines by a new
      electrochemical method and its correlation with polyphenolic content.
AB  - A new method for measuring the antioxidant power of wine has been developed based
      on the accelerated electrochemical oxidation of 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) (ABTS). The calibration (R = 0.9922) and
      repeatability study (RSD = 7%) have provided good statistical parameters. The
      method is easy and quick to apply and gives reliable results, requiring only the
      monitoring of time and absorbance. It has been applied to various red and white
      wines of different origins. The results have been compared with those obtained by
      the total antioxidant status (TAS) method. Both methods reveal that the more
      antioxidant wines are those with higher polyphenolic content. From the HPLC study
      of the polyphenolic content of the same samples, it is confirmed that there is a
      positive correlation between the resveratrol content of a wine and its
      antioxidant power.

PMID- 12009972
TI  - Development of a fluorescence polarization assay for the determination of
      aflatoxins in grains.
AB  - Aflatoxins produced by Aspergillus flavus are commonly found in human and animal
      foods including grains, cereals, peanut products, sorghum, and soy seeds.
      Exposure to aflatoxins has been associated with carcinogenicity. This paper
      reports a simple, portable, and rapid fluorescence polarization (FP) assay for
      aflatoxin determination in grains. This immunoassay is field portable,
      homogeneous, and without any washing and cleaning steps. The assay is based upon
      the competition between free aflatoxin and an aflatoxin-fluorescein tracer for an
      aflatoxin-specific monoclonal antibody in solution. A series of naturally
      contaminated corn, sorghum, peanut butter, and peanut paste samples were analyzed
      by FP and compared with HPLC results. Similarly, spiked popcorn samples were
      analyzed by FP. FP results of naturally contaminated samples correlated well with
      HPLC (r (2) = 0.97). FP analysis of spiked popcorn samples (with a mixture of
      B(1)/B(2)/G(1)/G(2), 7/1/3/1, w/w) gave a good correlation with spiked values (r
      (2) = 0.99). However, FP consistently underestimated the aflatoxin contents. This
      was perhaps due to low cross-reactivity of the antibody used toward B(2), G(1),
      and G(2) aflatoxins. These results combined with the portability and simplicity
      of the assay suggest that the assay can be used for screening total aflatoxin in
      grains.

PMID- 12009973
TI  - Analysis of antioxidant activities of common vegetables employing oxygen radical
      absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a
      comparative study.
AB  - A total of 927 freeze-dried vegetable samples, including 111 white cabbages, 59
      carrots, 51 snap beans, 57 cauliflower, 33 white onions, 48 purple onions, 130
      broccoli, 169 tomatoes, 25 beets, 88 peas, 88 spinach, 18 red peppers, and 50
      green peppers, were analyzed using the oxygen radical absorption capacity (ORAC)
      and ferric reducing antioxidant capacity (FRAP) methods. The data show that the
      ORAC and FRAP values of vegetable are not only dependent on species, but also
      highly dependent on geographical origin and harvest time. The two antioxidant
      assay methods, ORAC and FRAP, also give different antioxidant activity trends.
      The discrepancy is extensively discussed based on the chemistry principles upon
      which these methods are built, and it is concluded that the ORAC method is
      chemically more relevant to chain-breaking antioxidants activity, while the FRAP
      has some drawbacks such as interference, reaction kinetics, and quantitation
      methods. On the basis of the ORAC results, green pepper, spinach, purple onion,
      broccoli, beet, and cauliflower are the leading sources of antioxidant activities
      against the peroxyl radicals.

PMID- 12009974
TI  - Assessment of strawberry aroma through SPME/GC and ANN methods. Classification
      and discrimination of varieties.
AB  - To provide an efficient and running analytical tool to strawberry plant breeders
      who have to characterize and compare the aromatic properties of new cultivars to
      those already known, a HS-SPME/GC-MS analysis method has been coupled with a
      statistical treatment method issued from the current development of artificial
      neuron networks (ANN), and more specifically, the unsupervised learning systems
      called Kohonen self-organizing maps (SOMs). So, 70 strawberry samples harvested
      at CIREF from 17 known varieties have been extracted by using a DVB/Carboxen/PDMS
      SPME fiber according to the headspace procedure, and then chromatographed. A
      panel of 23 characteristic aromatic constituents has been selected according to
      published results relative to strawberry aroma. The complex resulting matrix,
      collecting the relative abundance of the 23 selected constituents for each
      sample, has been input into the SOM software adapted and optimized from the
      Kohonen approach described by one of the authors. After a period of training, the
      self-organized system affords a map of virtual strawberries to which real samples
      are compared and plotted in the best matching unit (BMU) of the map. The
      efficiency for discriminating the real samples according to their variety is
      dependent on the number of units selected to define the map. In this case, a 24
      unit map allowed the complete discrimination of the 17 selected varieties.
      Moreover, to test the validity of this approach, two additional samples were
      blind-analyzed and the results were computed according to the same procedure. At
      the end of this treatment, both samples were plotted into the same unit as those
      of the same variety used for training the map.

PMID- 12009975
TI  - Mycoactive acetate esters from apple fruit stimulate adhesion and germination of
      conidia of the gray mold fungus.
AB  - Ethyl acetate, 2-methylbutyl acetate, butyl acetate (BA), and hexyl acetate were
      detected by solid-phase microextraction and gas-liquid chromatography inside
      slices of Golden Delicious apple and in water droplets on the skin of slices
      incubated in sealed glass jars. Conidial adhesion and germination of the gray
      mold fungus, Botrytis cinerea, was assessed on apple slices after exposure or no
      exposure to the esters in the headspaces of glass jars. Attached conidia were
      dislodged by sonication and remaining conidia on apple slices were counted by
      microscopy. Adhesion generally increased as BA increased to 7.2 microg mL(-1),
      but declined with greater concentrations. BA at 0-3.6 microg mL(-1) for 24 h
      stimulated adhesion 2-fold greater compared to that at 4 h. Adhesion stimulated
      by BA increased as a function of time (0-24 h), showing linear trends (r (2) =
      0.99; p = 0.01) during 0-12 h. The four esters were similar in their ability to
      stimulate adhesion. Germination of conidia exposed to BA increased linearly (r
      (2) = 0.95-0.98; p = 0.01) during 4-12 h. Conidial adhesion stimulated by BA
      preceded conidial germination by 2 h. The four esters stimulated conidial
      germination to similar levels. Results indicated that acetate esters formed in
      apple fruit are mycoactive, influencing life-cycle events of B. cinerea important
      to its survival on the fruit. The similar responses of three B. cinerea isolates
      to four acetate esters suggests a common stimulation mechanism may operate in B.
      cinerea.

PMID- 12009976
TI  - Acylated and non-acylated flavonol monoglycosides from the Indian minor spice
      Nagkesar (Mammea longifolia).
AB  - A methanol extract of nagkesar (buds of Mammea longifolia), which showed strong
      radical scavenging activity, yielded 13 compounds by separations using column
      chromatography and HPLC. Structure elucidation of these compounds was achieved by
      (1)H and (13)C NMR, including DQF-COSY, TOCSY, DEPT, HMQC, HSQC, and HMBC. They
      include two new compounds, quercetin 3-O-(2' ',4' 'di-E-p-coumaroyl)-alpha-L
      rhamno-pyranoside and quercetin 3-O-(3' ',4' '-di-E-p-coumaroyl)-alpha-L
      rhamnopyranoside, along with known compounds kaempferol, quercetin, the
      isopropylidenedioxy derivative of shikimic acid, kaempferol 3-O-(2' ',4' '-di-E-p
      coumaroyl)-alpha-L-rhamnopyranoside, kaempferol 3-O-(3' ',4' '-di-E-p-coumaroyl)
      alpha-L-rhamnopyranoside, kaempferol 3-O-alpha-L-rhamnopyranoside, quercetin 3-O
      alpha-L-rhamnopyranoside, shikimic acid, kaempferol 3-O-beta-D-glucopyranoside,
      quercetin 3-O-beta-D-glucopyranoside, and beta-sitosterol 3-O-beta-D
      glucopyranoside.

PMID- 12009977
TI  - Essential oil constituents and in vitro antimicrobial activity of Decalepis
      hamiltonii roots against foodborne pathogens.
AB  - Hydrodistillation of Decalepis hamiltonii roots yielded an essential oil (0.33%
      v/w) that contained 2-hydroxy-4-methoxybenzaldehyde (37.45%), 2
      hydroxybenzaldehyde (31.01%), 4-O-methylresorcylaldehyde (9.12%), benzyl alcohol
      (3.16%), and alpha-atlantone (2.06%) as major constituents, with aromatic
      aldehydes constituting the main fraction of this root's essential oil. The oil
      was tested for its antimicrobial activity against foodborne pathogens responsible
      for food spoilage and human pathologies using standard antimicrobial assays. It
      exhibited strong antimicrobial activity against Bacillus cereus, Bacillus
      megaterium, Candida albicans, Escherichia coli, Micrococcus luteus, Micrococcus
      roseus, and Staphylococcus aureus at a concentration range of 1:0 with inhibitory
      activities of 27, 23, 16, 19, 22, 19, and 23 mm, respectively, which are
      comparable to those of the standards. The roots of D. hamiltonii, therefore, may
      be considered as an inexpensive source of an essential oil rich in antimicrobial
      compounds against foodborne pathogens.

PMID- 12009978
TI  - Biologically active secondary metabolites from Ginkgo biloba.
AB  - Three new compounds, (7E)-2beta,3alpha-dihydroxy-megastigm-7-en-9-one (1), 3-[5,7
      dihydroxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-8-yl]-4-methoxybenzoic acid (2),
      and 4'-O-methyl myricetin 3-O-(6-O-alpha-L-rhamnopyranosyl)-beta-D
      glucopyranoside (3), were isolated from Ginkgo biloba, together with 27 known
      compounds. The structures of the new compounds were determined primarily from 1D-
      and 2D-NMR analysis. The 4-O-methylbenzoic acid structural feature at C-8 in 2 is
      encountered for the first time. The antioxidant activities of 29 compounds
      isolated from Ginkgo biloba were evaluated on intracellular reactive oxygen
      species in HL-60 cells. It was found that quercetin, kampferol, and tamarixetin
      had antioxidant activity that was approximately 3-fold greater than that of their
      respective glycosides and also approximately 3-fold greater than that of a
      standard ascorbic acid with an IC(50) at maximum effectiveness.

PMID- 12009979
TI  - Can apple antioxidants inhibit tumor cell proliferation? Generation of H(2)O(2)
      during interaction of phenolic compounds with cell culture media.
AB  - It has recently been suggested that the ability of apple extracts to inhibit
      proliferation of tumor cells in vitro may be due to phenolic/flavonoid
      antioxidants. Our study demonstrates that this inhibition is caused indirectly by
      H(2)O(2) generated through interaction of the phenolics with the cell culture
      media. The results indicate that many previously reported effects of flavonoids
      and phenolic compounds on cultured cells may result from similar artifactual
      generation of oxidative stress. We suggest that in order to prevent such
      artifacts, the use of catalase and/or metmyoglobin in the presence of reducing
      agents should be considered as a method to decompose H(2)O(2) and prevent
      generation of other reactive oxygen species, which could affect cell
      proliferation. The use of tumor cells and "nontumor cells" in a bioassay to
      measure antioxidant activity, in this context, is potentially misleading and
      should be applied with caution.

PMID- 12009980
TI  - Detection of genetically modified coho salmon using polymerase chain reaction
      (PCR) amplification.
AB  - A PCR-based protocol for the identification of genetically modified salmon
      carrying a growth hormone transgene was developed. Several primer pairs were
      examined, and the primers that gave consistent results were selected to conduct
      routine testing. Comparison among several DNA extraction procedures, as well as
      different buffer compositions, led to the adoption of TriZol as the method of
      choice. Low potassium and high magnesium chloride concentrations were very
      important in the overall success of the PCR reaction, whereas buffer pH, ranging
      from 8.3 to 9.2, had little impact on the amplification reaction. The optimal
      primer annealing temperature was 52 degrees C. Although fish muscle tissues were
      the primary source for DNA samples, detection of the transgene was also possible
      in bones, skin, fins, and other organs. No benefits were achieved by the addition
      of additives such as dimethyl sulfoxide and betaine to the PCR reaction. This
      optimized PCR method was used to identify all samples tested (61 samples and 17
      controls) with 100% accuracy.

PMID- 12009981
TI  - Cloning and expression of desoxyhemigossypol-6-O-methyltransferase from cotton
      (Gossypium barbadense).
AB  - Terpenoids play an important role in defense against insects and pathogens in
      cotton. These terpenoids contain phenolic groups. Metabolites in which the
      phenolic group has been converted to a methoxy group are less toxic to most
      insects and pathogens and thus may alter resistance. Here is reported the cloning
      of a gene from Gossypium barbadense that encodes the enzyme that methylates the
      phenolic group of desoxyhemigossypol (dHG) exclusively at the 6-position, dHG-6-O
      methyltransferase (dHG-6-OMT). Partial peptide sequences from digests of purified
      dHG-6-OMT were used to design primers for RT-PCR amplification of cDNA fragments
      from poly(A) mRNA. Fragments were extended to full length using 5' and 3' RACE.
      The resulting cDNA codes for a 365-residue polypeptide with a calculated
      molecular weight of 40.6 kDa, in agreement with the molecular mass of purified
      dHG-6-OMT. When expressed in Escherichia coli, the bacterial lysates showed a
      high specificity for the methylation of desoxyhemigossypol, differentiating the
      cloned gene from other pathogen-induced methyltransferases.

PMID- 12009982
TI  - Evolution of the aroma profile of sherry wine vinegars during an experimental
      aging in wood.
AB  - Changes in the aroma profile of five Sherry wine vinegars submitted to an
      experimental static aging in wood were followed along 24 months. Eighteen
      volatile compounds were determined by GC-FID. The results were subjected to
      multivariate analyses: principal component analysis and linear discriminant
      analysis. The aroma profile of vinegar can be useful to discriminate vinegars
      produced from different substrates or with different aging times. During the
      experimental aging, volatile compounds such as methyl acetate, methanol,
      diacetyl, and gamma-butyrolactone underwent significant concentration increases.
      Moreover, the initial ethanol content of vinegars is a factor in the final
      aromatic richness. The formation of ethyl acetate stood out in samples with an
      initial ethanol content of approximately 2 alcoholic degrees.

PMID- 12009983
TI  - Structural changes in apple rings during convection air-drying with controlled
      temperature and humidity.
AB  - The structure of heat pump dried apple slices, developed as a function of air
      temperature and constant humidity, was studied by measuring porosity and using
      electron microscopy. The porosity of the apple rings increased linearly when the
      moisture content decreased during drying and then reached a constant value. In
      all dried apple slices, a degree of cellular collapse occurred. Case hardening
      occurred in the surface of the dried tissue when the apple slices were dried at
      40-45 and 60-65 degrees C, and in the extreme case (at 60-65 degrees C) cracks
      were formed on the surface.

PMID- 12009984
TI  - Ellagic acid and flavonoid antioxidant content of muscadine wine and juice.
AB  - Antioxidant properties of flavonoids and ellagic acid were characterized in eight
      wines and juices produced by various processing methodologies from red and white
      muscadine grape cultivars (Vitis rotundifolia). Juices and wines were produced by
      hot- and cold-pressed techniques, and additional wine was produced following on
      hull fermentation for 3, 5, and 7 days. Chromatographic conditions were developed
      to simultaneously separate anthocyanins, ellagic acid, and flavonols and
      correlated to a measurement of overall antioxidant capacity (AOX), and their
      changes were monitored after storage for 60 days at 20 and 37 degrees C.
      Regression coefficients between concentrations of individual polyphenolics and
      AOX ranged from 0.55 for ellagic acid to 0.90 for kaempferol. Both red and white
      wines had higher AOX values after storage than juices made from an identical
      grape press, despite lower concentrations of individual polyphenolic compounds.
      Red wines fermented on-hull had higher initial concentrations of antioxidant
      polyphenolics as compared to a corresponding hot-pressed juice, but changes in
      AOX during storage were more affected by time than by storage temperature despite
      lower concentrations of flavonoids and ellagic acid present at 37 degrees C as
      compared to 20 degrees C. Oxidative or polymerization reactions significantly
      decreased levels of monomeric anthocyanins during storage with the greatest
      losses observed for delphinidin and petunidin 3,5-diglucosides. Processing
      methods for muscadine wine and juice production were important factors
      influencing concentrations of antioxidant flavonoids and ellagic acid, while the
      role of fermentation and time had the greatest influence on retention of AOX
      properties during storage.

PMID- 12009985
TI  - Rapid and convenient method for preparing aurapten-enriched product from hassaku
      peel oil: implications for cancer-preventive food additives.
AB  - Aurapten (7-geranyloxycoumarin) has been reported to be an effective inhibitor of
      chemical carcinogenesis in some rodent models. In the present study, a method for
      preparing an aurapten-enriched agricultural product has been established. Out of
      17 Rutaceae varieties, the aurapten content in hassaku (Citrus hassaku Hort ex Y.
      Tanaka) fruit peel was marked, as well as that in natsumikan (C. natsudaidai) and
      grapefruit (C. paradisi). The aurapten content in hassaku peel was most abundant
      in April. Hassaku fruit peel oil, which was dissolved by heating precipitates
      including aurapten which had formed after freezing the peel oil at -20 degrees C,
      was used. After adsorbing aurapten from peel oil onto synthetic adsorbent SP70,
      the adsorbent was washed with 40% (v/v) ethanol in water to remove essential oils
      and pigments remaining on the adsorbent. Aurapten was then eluted with 80% (v/v)
      ethanol. In a laboratory-scale test, the recovery rates of aurapten and total
      carotenoids from the eluates were 74.3 and 4.6%, respectively. In a pilot-scale
      test, the recovery rate of aurapten in the aurapten-enriched preparation from
      dissolved hassaku oil was 91.0%, and its concentration was 64.1% (w/w). When
      stored for 180 days under sunlight, aurapten in powder form remained at 88.0
      89.0% of the initial level, but only 31.3-43.8% in ethanol. The stability of
      aurapten in the aurapten-enriched preparation was higher than that of purified
      aurapten. These results suggest that aurapten is readily recovered from hassaku
      peel oil using SP70, and thus may be used as a food additive.

PMID- 12009986
TI  - Effect of storage on wall-bound phenolics in green asparagus.
AB  - The cell walls of green asparagus spears have been analyzed for their phenolic
      and carbohydrate composition as modified by postharvest storage. Esterified
      phenolic components were released by sequential alkaline hydrolysis and
      identified and quantified by diode array HPLC. Significant quantities of ferulic
      acid (FA) and its derivatives were found to increase at least 3-fold during
      storage, particularly in walls from the lower parts of the stem, where
      accompanying changes in sugar composition were also observed. In fresh asparagus,
      >60% of the total FA was in the form of diferulic acid, and this increased to
      approximately 70% after 3 days of storage. The main FA dehydrodimers were 8-8-, 8
      O-4-, and 8-5-diferulates. These have been detected in other monocotyledonous and
      dicotyledonous plants, but as a smaller proportion of the total FA. The possible
      roles phenolic esters might have in relation to the mechanical, textural, and
      wound-response properties of asparagus spears are discussed.

PMID- 12009987
TI  - Comparison of soxhlet and microwave-assisted extractions for the determination of
      fenitrothion residues in beans.
AB  - White and black "niebe" beans [Vigna unguiculata (L.) Walp] from Senegal were
      treated with fenitrothion (O,O-dimethyl O-4-nitro-m-tolyl phosphorothioate), and
      the residues were determined by high-performance liquid chromatography (HPLC) and
      electron capture gas chromatography (EC-GC). Fenitrothion residues from the beans
      were extracted by Soxhlet extraction (SE) and microwave-assisted extraction
      (MAE). A column cleanup procedure was used to remove the coextractives in the
      extract before HPLC and EC-GC analyses. The overall mean recoveries of
      fenitrothion residues in the 0.19-1.90 microg/kg fortification range determined
      from extracts obtained by SE and MAE were 88.4 and 89.8%, respectively, with
      respective relative standard deviations of <4%. The results show that MAE is a
      viable alternative to the commonly used SE for the determination of fenitrothion
      residues in beans.

PMID- 12009988
TI  - Antimycotic activities of selected plant flora, growing wild in Lebanon, against
      phytopathogenic fungi.
AB  - Petroleum ether (PE) and methanolic extracts of nine wild plant species were
      tested in vitro for their antimycotic activity against eight phytopathogenic
      fungi. The efficacy of PE extracts against all pathogens tested was higher than
      that of methanolic extracts. Wild marjoram (Origanum syriacum) PE extract showed
      the highest and widest range of activity. It resulted in complete inhibition of
      mycelial growth of six of eight fungi tested and also gave nearly complete
      inhibition of spore germination of the six fungi included in the assay, namely,
      Botrytis cinerea, Alternaria solani, Penicillium sp., Cladosporium sp., Fusarium
      oxysporum f. sp. melonis, and Verticillium dahlia. The other plant extracts
      showed differential activities in the spore germination test, but none was highly
      active against mycelial growth. Inula viscosa and Mentha longifolia were highly
      effective (>88%) in spore germination tests against five of six fungi tested,
      whereas Centaurea pallescens, Cichorium intybus, Eryngium creticum, Salvia
      fruticosa, and Melia azedarach showed >95% inhibition of spore germination in at
      least two fungi. Foeniculum vulgare showed the least antimycotic activity.
      Fractionation followed by autobiography on TLC plates using Cladosporium sp. as a
      test organism showed that O. syriacum PE extracts contained three inhibition
      zones, and those of Inula viscosa and Cichorium intybus, two, whereas the PE
      extracts of the remaining plants showed each one inhibition zone. Some of the
      major compounds present in these inhibition zones were identified by GC-MS. The
      possibility for using these extracts, or their mixtures, to control plant
      diseases is discussed.

PMID- 12009989
TI  - Synthesis, rheological characterization, and constitutive modeling of polyhydroxy
      triglycerides derived from milkweed oil.
AB  - Asclepias syriaca L., the common milkweed, is a new industrial crop. The seed
      contains about 20-30 wt % of a highly unsaturated oil having unusual fatty acids.
      Exploring value-added products from the oil, milkweed triglycerides have been
      oxidized by in situ performic acid to the polyoxirane and polyhydroxy
      triglycerides (PHTG). The rheological properties of milkweed PHTG were
      characterized in various shear flows. Milkweed PHTG displayed nonlinear
      viscoelastic behavior at applied strains greater than 1%. Milkweed PHTG was found
      to obey time-strain separability. A nonlinear Wagner constitutive model was used
      successfully to qualitatively predict the behavior of milkweed PHTG in both start
      up and cessation of steady-state shear flow.

PMID- 12009990
TI  - Evidence for the biosynthetic pathway from sinapic acid to syringyl lignin using
      labeled sinapic acid with stable isotope at both methoxy groups in Robinia
      pseudoacacia and Nerium indicum.
AB  - A tracer experiment using synthesized labeled lignin precursors was designed to
      confirm the actual biosynthetic pathway for syringyl lignin. Tetradeuteroferulic
      acid-[8-D, 3-OCD(3)] and heptadeuterosinapic acid-[8-D, 3,5-OCD(3)] were
      synthesized and fed to shoots of robinia (Robinia pseudoacacia) and oleander
      (Nerium indicum) trees. The incorporation of each labeled precursor into lignin
      was traced by gas chromatography-mass spectrometry. The synthesized sinapic acid,
      in which both methoxy groups were labeled, was useful in monitoring the
      conversion of sinapic acid into syringyl lignin. When heptadeuterosinapic acid
      was fed, syringyl units containing seven deuterium labels were detected. The
      results of this study support the traditionally accepted pathway that sinapic
      acid is converted to sinapyl alcohol via sinapoyl-CoA in robinia and oleander.

PMID- 12009991
TI  - Anthocyanins from black currants (Ribes nigrum L.).
AB  - Fifteen anthocyanin structures are reported from an extract of black currant
      berries (Ribes nigrum L.). These are the 3-O-glucosides and the 3-O-rutinosides
      of pelargonidin, cyanidin, peonidin, delphinidin, petunidin, and malvidin,
      cyanidin 3-O-arabinoside, and the 3-O-(6' '-p-coumaroylglucoside)s of cyanidin
      and delphinidin. The anthocyanins were characterized by means of size exclusion
      chromatography, high-performance liquid chromatography, UV-visible spectroscopy,
      and electrospray mass spectrometry. The four main pigments (the 3-O-glucosides
      and the 3-O-rutinosides of delphinidin and cyanidin) made up >97% of the total
      anthocyanin content. The minor pigments were enriched from the extract by
      successive partition against ethyl acetate and by gel fractionation. These
      chromatographic steps were successfully used to isolate the acylated anthocyanins
      from the ethyl acetate layer and to separate cyanidin 3-O-arabinoside from the
      mixture of anthocyanins. The amounts of anthocyanin rutinosides were found to be
      higher than the amount of the corresponding glucosides for all detected pigments
      having the same aglycon moiety.

PMID- 12009992
TI  - Heat shocks increase the chilling tolerance of rice (Oryza sativa) seedling
      radicles.
AB  - The growth of rice (Oryza sativa L., cv. M202) seedling radicles, initially 10 +/
      1 mm long, was linear for the 96 h it took them to grow to 150 mm at 25 degrees
      C. Exposure to 5 degrees C for 24 h reduced the rate of growth by about 50%, and
      longer exposures caused a progressive reduction in growth. Initial radicle length
      significantly affected chilling sensitivity: with 2 days at 5 degrees C
      inhibiting growth at 25 degrees C by 23% for 1-mm radicles, 63% for 10-mm
      radicles, and 87% for 40-mm radicles. Heat shocks of 35 degrees C for 4 min, 40
      degrees C for 3 min, 45 degrees C for 2 min, or 50 degrees C for 1 min, prior to
      chilling, reduced the 75% inhibition of radicle growth caused by 2 days at 5
      degrees C to 34%, 25%, 14%, and 13%, respectively. The length of exposure that
      conferred chilling tolerance increased from less than 2 min for 50 degrees C to
      over 8 min for 35 degrees C. This increase in effective treatment duration was
      accompanied by a reduction in the maximum induced chilling tolerance. Practical
      application of heat-shock treatments to increase the chilling tolerance of rice
      seedlings may sacrifice a small reduction in maximum chilling tolerance at the
      lower inductive temperatures for a larger margin of safety in their application.

PMID- 12009993
TI  - Effects of soil pH and soil water content on prosulfuron dissipation.
AB  - The sulfonylurea herbicide prosulfuron, 1-(4-methoxy-6-methyltriazin-2-yl)-3-[2
      (3,3,3-trifluoropropyl)phenylsulfonyl]urea, is used for the selective control of
      broadleaf weeds in corn, sorghum, and cereal grains. To investigate its fate in
      soils, this study examined the effects of soil pH and water content on the rates
      of dissipation processes and the products formed under aerobic conditions.
      Radiometry and chromatography analyses were used to quantify the degradation
      products and bound residues formed in incubations of 10 different soils. The pH
      dependent hydrolysis of the sulfonylurea bridge to form phenyl sulfonamide was
      the primary transformation process. Significant microbial degradation of
      prosulfuron occurred in 2 of the 10 soils, yielding (14)CO(2) and desmethyl
      prosulfuron among the major products. The time required for 50% dissipation of
      the herbicide (DT(50)) was determined for each soil and water content treatment.
      At equivalent water contents, prosulfuron DT(50) values were positively
      correlated with soil pH (P < 0.0001), varying from 6.5 days at pH 5.4 to 122.9
      days at pH 7.9. Soil pH and water content strongly influence the fate of
      sulfonylurea herbicides in agricultural fields. Differences in the effect of soil
      water content on dissipation kinetics in a comparison of two soils were
      attributed to differences in soil pH, texture, and the ability of indigenous
      microorganisms to transform the herbicide.

PMID- 12009994
TI  - Environmental fate of spinosad. 1. Dissipation and degradation in aqueous
      systems.
AB  - Spinosad is a bacterially derived insect control agent consisting of two active
      compounds, spinosyns A and D. The objective of this paper is to describe the
      environmental fate of spinosad in aquatic systems. To this end, several studies
      performed to meet regulatory requirements are used to study the fate and
      degradation in individual environmental media. Specifically, investigations of
      abiotic (hydrolysis and photolysis) and biotic (aerobic and anaerobic aquatic)
      processes are described. Understanding developed from the laboratory-based
      studies has been tested and augmented by an outdoor microcosm study.
      Understanding of aquatic fate is a building block for a complete environmental
      safety assessment of spinosad products (Cleveland, C. B.; Mayes, M. A.; Cryer, S.
      A. Pest Manag. Sci. 2001, 58, 70-84). From individual investigations, the
      following understanding of dissipation emerges: (1) Aqueous photolysis of
      spinosad is rapid (observed half-lives of <1 up to 2 days in summer sunlight) and
      will be the primary route of degradation in aquatic systems exposed to sunlight.
      (2) Biotic transformations contribute to spinosad's dissipation, but less so than
      photolysis; they will be of primary importance only in the absence of light. (3)
      Spinosad partitions rapidly (within a few days) from water to organic matter and
      soil/sediment in aquatic systems but not so rapidly as to replace sunlight as the
      primary route of dissipation. (4) Abiotic hydrolysis is relatively unimportant
      compared to other dissipation routes, except under highly basic (artificial)
      conditions and even then observed half-lives are approximately 8 months.
      Degradation pathways are understood are follows: (1) Degradation primarily
      proceeds by loss of the forosamine sugar and reduction of the 13,14-bond on the
      macrolide ring under aqueous photolytic conditions. (2) Degradation to several
      other compounds occurs through biotic degradation. Degradation under anaerobic
      conditions primarily involves changes and substitutions in the rhamnose ring,
      eventually followed by complete loss of the rhamnose ring. Degradation under
      aerobic conditions was more extensive (to smaller compounds) with the loss of
      both the forosamine and rhamnose sugars to diketone spinosyn aglycon degradates.
      (3) Hydrolytic degradation involves loss of the forosamine sugar and water and
      reduction on the macrolide ring to a double bond at the 16,17-position.

PMID- 12009995
TI  - Ground red peppers: capsaicinoids content, Scoville scores, and discrimination by
      an electronic nose.
AB  - High-pressure liquid chromatography (HPLC) was used to determine the capsaicin,
      dihydrocapsaicin, and total capsaicinoids levels of different ground red pepper
      samples obtained from local retail markets in Izmir, Turkey. Scoville scores were
      determined using sensory tests. An electronic nose (EN) was used to discriminate
      ground red pepper samples by headspace volatiles. EN data were analyzed using
      discriminant function analysis (DFA). An overall correct classification rate of
      pepper varieties by EN of 91% was obtained. A linear correlation between
      capsaicin, dihydrocapsaicin, and total capsaicinoids and Scoville scores was also
      observed, and R (2) values of 0.89, 0.85, and 0.91 were obtained, respectively.

PMID- 12009996
TI  - Sensory and chemical changes in tomato sauces during storage.
AB  - The present work aimed to identify the key odorants of tomato sauces responsible
      for the flavor change during storage. Products made from paste or canned tomatoes
      were stored at 25 and 40 degrees C. Sensory properties and quantification of the
      key odorants were measured and correlated. Significant sensory changes appeared
      after 1 and 3 months at 25 degrees C in the respective dice and paste sauces (p <
      0.01). The dice sauce was characterized by a steep loss of the sensory quality
      during the early storage and then by identical changes within the same time span
      at 25 and 40 degrees C. In the paste sauce the sensory deterioration was slower
      than for the dice sauce and occurred more extensively at 40 degrees C than at 25
      degrees C. Correlation between sensory and instrumental data revealed that the
      source of sensory changes should be (E,E)-deca-2,4-dienal in the dice sauce. The
      sensory change in the paste sauce could be due to acetaldehyde, methylpropanal, 3
      methylbutanal, oct-1-en-3-one, 3-methylbutanoic acid, deca-2,4-dienal, 2
      methoxyphenol, and beta-damascenone.

PMID- 12009997
TI  - Maturing wines in oak barrels. Effects of origin, volume, and age of the barrel
      on the wine volatile composition.
AB  - The influence of the oak origin, volume, and age of the barrel on the volatile
      composition of a red wine after six months of maturation have been studied. Major
      volatile compounds in wine were determined using liquid-liquid extraction with
      dichloromethane, and those volatiles being due to the oak were determined by
      extraction with pentane-ether using deuterated analogues as internal standards.
      The results show that there is little difference between the volatile composition
      of wines matured in French oak barrels and those matured in American oak barrels.
      The concentration of cis-oak lactone was the most significant difference. The
      greatest instrumental and sensory differences were found between new and used
      barrels, with important decreases in lactones and vanillin concentration in used
      barrels. When studying the effect of the volume of the barrel, the
      characteristics of the wine matured in 220-L new barrels versus those matured in
      1000-L new barrels were very different. In new barrels, the larger the volume of
      the barrel, the lower the concentrations of those compounds responsible for the
      oaky aroma. These differences were less evident when comparing wines matured in
      used barrels with different capacities.

PMID- 12009998
TI  - Impact odorants contributing to the fungus type aroma from grape berries
      contaminated by powdery mildew (Uncinula necator); incidence of enzymatic
      activities of the yeast Saccharomyces cerevisiae.
AB  - Powdery mildew due to the fungus Uncinula necator is an important disease for the
      vineyard. The development of the fungus at the surface of the berries leads to
      the occurrence of a very characteristic and sometimes intense mushroom-type odor
      cited as an important default for grapes quality. Gas
      chromatography/olfactometry, gas chromatography, and multidimensional gas
      chromatogaphy/mass spectrometry techniques were used to investigate the most
      important odorants of grapes diseased by powdery mildew. Among 22 odorants
      detected, strongly odorant compounds were identified or tentatively identified in
      purified extracts obtained from grapes diseased by powdery mildew. Aroma
      extraction dilution analysis (AEDA) analysis revealed that 1-octen-3-one
      (mushroom odor), (Z)-1,5-octadien-3-one (geranium-leaf odor), and an unidentified
      odorous zone (fishy-mushroom like odor) were the most potent volatiles of the
      diseased grapes. In the presence of nonproliferating Saccharomyces cerevisiae
      yeast cells, and consequently during alcoholic fermentation, the enzymatic
      reduction of 1-octen-3-one and (Z)-1,5-octadien-3-one to much less odorant
      compounds, namely 3-octanone and (Z)-5-octen-3-one, was shown. Those results
      explain to some extent the disappearance of the fungal aroma specific to powdery
      mildew grapes during alcoholic fermentation.

PMID- 12009999
TI  - Influence of human salivary enzymes on odorant concentration changes occurring in
      vivo. 1. Esters and thiols.
AB  - The influence of human whole saliva on odor-active esters and thiols was
      investigated. Special emphasis was placed on food-relevant concentrations of the
      odorants. It was found that the amounts of the esters were reduced during
      incubation with saliva to different extents according to their chemical
      structures. Considerable degradations were also observed for 2-furfurylthiol, 2
      phenylethanethiol, and 3-mercapto-3-methyl-1-butanol, being reduced from
      approximately 70 to 20% of their initial concentrations within a period of 10
      min. Decrease of the odorants did not occur after thermal treatment of the
      saliva. Generally, the enzymic processes were found to be dependent on the
      salivary activity of each individual panelist as well as on the odorant's
      concentrations applied. These investigations were aimed at finding an explanation
      for the persistence of aftertaste in humans, as it is induced by some odor-active
      compounds after the consumption of food materials.

PMID- 12010000
TI  - Oxidation of ferulic acid or arabinose-esterified ferulic acid by wheat germ
      peroxidase.
AB  - The oxidation of ferulic acid (FA) or 5-O-(trans-feruloyl)-L-arabinose (EFA) by a
      purified wheat germ peroxidase was followed by UV spectrophotometry and high
      performance liquid chromatography using an electrochemical detection. Wheat
      peroxidase (POD) exhibits a ping-pong bireactant mechanism forming phenoxy
      radicals more rapidly from FA than from EFA in routine assay conditions. When
      both the free and the esterified forms of FA are present, the reverse was found.
      This result could be due to a nonenzymatic cooxidation of FA by the phenoxy
      radicals of EFA leading to the formation of phenoxy radicals of FA and the EFA
      regeneration. Addition of ascorbic acid (AA) provokes a delay of FA consumption.
      AA reduced very rapidly the phenoxy radicals formed by POD back to initial phenol
      avoiding the formation of ferulate dimers until it was completely oxidized in
      dehydroascorbic acid. Conversely, cysteine addition slowed but did not delay the
      FA consumption. The thiol reduced a fraction of the phenoxy radicals produced by
      wheat POD and was oxidized into cystine, while the other part of phenoxy radicals
      formed ferulate dimers. These results could be of interest to understand the POD
      effect on the wheat dough rheological properties.

PMID- 12010001
TI  - Influence of procyanidins on the color stability of oenin solutions.
AB  - The aim of the present work was to specify the influence of the polymerization
      degree on the color stability of anthocyanins using model solutions under higher
      thermal conditions simulating rapid food aging. Results showed that an increase
      in polymeric degree improves the color stability of oenin. Solutions containing a
      catechin tetramer, purified from brown rice, displayed a remarkable stability.
      Flavanols as monomers, (+)-catechin and (-)-epicatechin, appeared to decrease
      stability with the formation of a xanthylium salt leading to yellowish solutions.
      For the dimers, procyanidin B2 and B3, different behaviors on red color stability
      have been observed corresponding to their different susceptibility to cleavage
      upon heating. In the presence of the trimeric procyanidin C2, the red color
      appeared more stable. However, the HPLC chromatograms showed a decrease in the
      amplitude of the peaks of oenin and procyanidin C2. Concomitantly, a new peak
      appeared with a maximal absorption in the red region. This newly formed pigment
      probably came from the condensation of oenin and procyanidin C2.

PMID- 12010002
TI  - Effect of endogenous triacylglycerol hydrolysates on the mechanical properties of
      Zein films from ground corn.
AB  - Dry-milled yellow corn and freshly ground food and nonfood grade yellow and white
      hybrid corn kernels were pretreated in a solution of lactic acid and sodium
      metabisulfite followed by extraction with 70% ethanol. Zein was precipitated from
      the extract by reducing the ethanol content of the extract to 40%. Lipid
      associated with the zein isolates was between 15 and 20% and contained mostly
      endogenous free fatty acids. The effect of the endogenous free fatty acids on
      zein isolate films, with and without free fatty acids, was determined by
      measuring various film properties. Stress-strain measurements indicated 40-200%
      greater elongation for zein films containing endogenous free fatty acids. Films
      prepared from zein isolated from preground corn stored for approximately 4 months
      (27 degrees C, 17% relative humidity) had approximately 3 times greater
      elongation values than zein films prepared from freshly ground corn.

PMID- 12010003
TI  - Modification of ascorbic acid using transglycosylation activity of Bacillus
      stearothermophilus maltogenic amylase to enhance its oxidative stability.
AB  - Ascorbic acid (1), a natural antioxidant, was modified by employing
      transglycosylation activity of Bacillus stearothermophilus maltogenic amylase
      with maltotriose and acarbose as donor molecules to enhance its oxidative
      stability. The transglycosylation reaction with maltotriose as donor created mono
      and di-glycosyl transfer products with an alpha-(1,6)-glycosidic linkage. In
      addition, two acarviosine-glucosyl transfer products were generated when
      transglycosylation was performed with acarbose as a donor. All transfer products
      were observed by TLC and HPLC, and purified by Q-sepharose anion exchange and
      Biogel P-2 gel permeation chromatographies. LC/MS and (13)C NMR analyses revealed
      that the structures of the transfer products were 6-O-alpha-D-glucosyl- (2) and 6
      O-alpha-D-maltosyl-ascorbic acids (3) in the reaction of maltotriose, and 6-O
      alpha-acarviosine-D-glucosyl- (4) and 2-O-alpha-acarviosine-D-glucosyl ascorbic
      acids (5) in the reaction of acarbose. The stability of the transglycosylated
      ascorbic acid derivatives was greatly enhanced against oxidation by Cu(2+) ion
      and ascorbate oxidase. Among them, compound 3 proved to be the most stable
      against in vitro oxidation. The antioxidant effects of glycosyl-derivatives of
      ascorbic acid on the lipid oxidation in cooked chicken breast meat patties
      indicated that they had antioxidant activities similar to that of ascorbic acid.
      It is suggested that the transglycosylated ascorbic acids can possibly be applied
      as effective antioxidants with improved stability in food, cosmetic, and other
      applications.

PMID- 12010004
TI  - Carbohydrate differences in strawberry crowns and fruit (Fragaria x ananassa)
      during plant development.
AB  - Carbohydrates accumulation and mobilization are highly relevant in plants because
      they have been related to yield and quality. Therefore, the aims of this work
      were to determine soluble carbohydrates and starch in strawberry (Fragaria x
      ananassa cv. Camarosa) crown sections (basal, middle, and upper) at three
      different plant growth stages (vegetative, blooming, and fruiting), and in fruit
      varieties (cv. Camarosa, Seascape, and Oso Grande) grown on the same field and in
      a different geoclimate. The main soluble carbohydrates found were glucose,
      sucrose, and fructose. Concentration differences were found among crown sections
      and time. The lowest levels of glucose, fructose, and sucrose were present at the
      beginning of fruit formation (6.2, 1.8 mg/g, and trace, respectively). Starch
      increased in basal and middle sections at the same time (8.6 to 109.6 and 6.6 to
      93.5 mg/g, respectively). There appears to be a relationship between crown and
      fruit soluble carbohydrates. The most abundant fruit monosaccharides in all
      varieties were glucose (160-190 mg/g), fructose (90-180 mg/g), and sucrose (30
      120 mg/g), followed by myo-inositol (10-23 mg/g). Strawberry crowns are an
      important source of carbohydrates and they might play a role during plant
      development specifically related to fruit sweetness. Fruit quality is highly
      influenced by a combination of several factors such as genotype, geoclimate, and
      probably carbon partitioning.

PMID- 12010005
TI  - Antioxidant properties of Antrodia camphorata in submerged culture.
AB  - The biologically active compounds, antioxidant activities, and free radical
      scavenging effects of dry matter of cultural medium (DMCM), filtrate (DMF), and
      different solvent extracts of mycelia from Antrodia camphorata in submerged
      culture (ACSC) were investigated. DMF showed the strongest inhibition of lipid
      peroxidation as a function of its concentration, and was comparable to the
      antioxidant activity of BHA at the same concentration of 0.2 mg/mL. The hexane
      extract of mycelia had the weakest antioxidant ability, whereas other mycelial
      extracts exhibited a modest inhibition of lipid peroxidation. DMF and water
      extract of mycelia (WEM) showed marked activity in free radical scavenging. The
      antioxidant activities of filtrate and mycelial extracts were correlated with the
      presence of total polyphenols, the crude triterpenoids, and the
      protein/polysaccharide ratio of the crude polysaccharides. It was found that DMCM
      had lower antioxidant ability than DMF in different model systems, indicating
      that the major antioxidant components in DMF must be derived from the secondary
      metabolites of mycelia. The results presented herein indicate that DMF could
      possibly act as a chemopreventing agent with respect to free radical-related
      diseases.

PMID- 12010006
TI  - Kinetic method for determining antioxidant distributions in model food emulsions:
      distribution constants of t-butylhydroquinone in mixtures of octane, water, and a
      nonionic emulsifier.
AB  - The absence of reliable estimates of distributions of antioxidants in food
      emulsions hinders the development of a useful method for comparing the
      efficiencies of antioxidants. Here we describe the application of a pseudophase
      kinetic model, originally developed for homogeneous microemulsions, to the
      determination of distribution constants of tert-butylhydroquinone, TBHQ, in a
      fluid, opaque, model food emulsion composed of the nonionic emulsifier C(12)E(6),
      octane, and water. This kinetic method should be applicable to a wide variety of
      charged and uncharged antioxidants in emulsions composed of charged and uncharged
      emulsifiers. The distribution constants for partitioning of TBHQ between the oil
      and surfactant film regions, K(O)(I), and the aqueous and surfactant film
      regions, K(W)(I), were obtained by fitting changes in first-order rate constants,
      k(obs), with emulsifier volume fraction for the reaction of 4-hexadecyl-2,6
      dimethylbenzenediazonium ion, 16-ArN(2)(+), with TBHQ. The rate of formation of
      the reduced arene product hexadecyl-2,6-dimethylbenzene, 16-ArH, was followed by
      HPLC. About 90% of the TBHQ is in the surfactant film at about 2% volume fraction
      of C(12)E(6), which suggests that this region may be the primary site of
      antioxidant activity for neutral phenolic antioxidants.

PMID- 12010007
TI  - Plant foods and herbal sources of resveratrol.
AB  - Stilbenes, in particular trans-resveratrol and its glucoside, are widely reported
      to be beneficial to health, having been shown to possess antioxidative,
      anticarcinogenic, and antitumor properties. Major dietary sources include grapes,
      wine, peanuts, and soy; however, they can also be introduced into the diet
      through Itadori tea, which has long been used in Japan and China as a traditional
      herbal remedy for heart disease and strokes. Analysis of grapes, peanuts, and
      Itadori tea shows that they contain mainly trans-resveratrol glucoside. In
      contrast, red wines are primarily a source of the aglycones cis- and trans
      resveratrol. While peanuts and grapes contain low levels of the stilbenes,
      Itadori tea and red wine both supply relatively high concentrations of
      resveratrol. For people who do not consume alcohol, Itadori tea may be a suitable
      substitute for red wine. However, further study on the potential biological
      effects of other endogenous compounds in Itadori tea is required and there is
      also a need for more information on the absorption and in vivo biomedical actions
      of free and conjugated resveratrol.

PMID- 12010008
TI  - Buckwheat extract inhibits progression of renal failure.
AB  - Rats subjected to partial resection of the parenchyma showed reduced radical
      scavenging activity in the remaining kidney and increased severity of renal
      tissue lesions. However, in similarly nephrectomized rats given buckwheat
      extract, the state of oxidative stress improved by restoring the decreased
      activities of reactive oxygen species-scavenging enzymes such as superoxide
      dismutase and catalase. The degree of mesangial proliferation, severity of
      extratubular lesions such as crescents and adhesions, glomerulosclerosis index,
      and severity of tubular interstitial lesions also improved. In addition,
      nephrectomized rats given buckwheat extract showed improvement in renal function,
      as indicated by decreased serum level of creatinine, with a significant decrease
      in the level of methylguanidine, a uremic toxin produced from creatinine in the
      presence of hydroxyl radical.

PMID- 12010009
TI  - A mixed green vegetable and fruit beverage decreased the serum level of low
      density lipoprotein cholesterol in hypercholesterolemic patients.
AB  - The effects of a canned mixed green vegetable and fruit beverage, containing
      broccoli (Brassica oleracea L. var. botrytis L.) and cabbage (Brassica oleracea
      L. var. capitata L.) as main materials, on serum lipid levels in
      hypercholesterolemic patients were investigated. Thirty-one adult subjects were
      administered two cans of the beverage (160 g/can) per day for 3 weeks. Their
      serum total cholesterol (TC) levels significantly decreased from 6.7 +/- 0.8 to
      6.1 +/- 0.6 mmol/L, and, more strikingly, the level of low-density lipoprotein
      cholesterol (LDL-C) significantly decreased from 4.4 +/- 0.8 to 3.8 +/- 0.7
      mmol/L. At 9 weeks after the cessation of the administration, these levels had
      returned to the preadministration levels. Furthermore, 14 other subjects who were
      administered one can of the sample for 12 weeks also showed a significant
      reduction in the levels of serum TC and LDL-C. Thus, daily consumption of this
      mixed green vegetable and fruit beverage may be useful in lowering serum TC and
      LDL-C levels in hypercholesterolemic patients.

PMID- 12010010
TI  - Detection and characterization of DNA adducts formed from metabolites of the
      fungicide ortho-phenylphenol.
AB  - The significance of DNA adduction in ortho-phenylphenol-induced carcinogenesis
      remains unclear. Establishing adduct structures may contribute to resolving this
      issue. The chemical structures of the DNA adduction products resulting from the
      in vitro reaction of phenylbenzoquinone, the putative ultimate carcinogenic
      metabolite of the fungicide/disinfectant ortho-phenylphenol, are reported here.
      Three isomeric adducts that resulted from reaction of deoxyguanosine were
      characterized by UV, LC-ESI-MS, and MS/MS, and 1D and 2D COSY-NMR spectroscopy.
      The proposed mechanism of product formation is nucleophilic attack by the
      deoxyguanosine exocyclic amine nitrogen on an electrophilic quinone carbon,
      followed by stabilization through enolization. Another nucleophilic attack forms
      a five-membered ring, which aromatizes by dehydration to form the final product.
      Adducts were also characterized from deoxyadenosine and deoxycytidine, although
      conversions were at least 10 times lower. Structures are also proposed for these
      products. Cell culture studies confirmed that HepG2 cells incubated with
      phenylbenzoquinone at concentrations associated with cytotoxicity form the same
      DNA adducts.

PMID- 12010011
TI  - Prediction of an inverse heavy-atom effect in H-C-CH(2)Br: bromine substituent as
      a pi acceptor.
AB  - A comparison of spin-orbit coupling calculated [CASSCF(6,6)/(cc-pVDZ on C,H and
      VDZ+P on Br] for bromomethylcarbene and methylcarbene predicts a highly unusual
      inverse heavy-atom effect by the Br substituent, particularly at geometries near
      the syn conformation. This behavior is due to a vacant 4d orbital on the Br atom
      acting as a weak pi-electron acceptor and overwhelming the even weaker effect of
      the pi-symmetry lone pair donor 4p orbital, which in itself would cause a small
      normal heavy-atom effect.

PMID- 12010012
TI  - Synthesis of MoVNbTe(Sb)O(x) composite oxide catalysts via reduction of
      polyoxometalates in an aqueous medium.
AB  - The synthesis of MoVNbTe(Sb)O(x)() composite oxide catalysts based on the self
      organization of polyoxometalates (POMs) was investigated. The catalysts which
      were synthesized via reduction of POMs by using reducing agents under mild
      conditions and/followed by calcination in an O(2)-excluded atmosphere which
      superior performance for propane (amm)oxidation. It was suggested that the
      metastable phase formed at an elevated temperature with a specific oxidation
      state corresponds to the catalytic activity.

PMID- 12010014
TI  - Isotactic-b-syndiotactic stereoblock poly(methyl methacrylate) by chiral
      metallocene/Lewis acid hybrid catalysts.
AB  - Stereoblock polymerization with chiral ansa-metallocene/strong Lewis acid hybrid
      catalysts capable of switching stereospecificity of the methyl methacrylate
      polymerization produces the highly stereoregular isotactic-b-syndiotactic
      stereoblock poly(methyl methacrylate).

PMID- 12010013
TI  - Liposomes from novel photolabile phospholipids: light-induced unloading of small
      molecules as monitored by PFG NMR.
AB  - A molecular dithiane-based approach to synthesis of novel photolabile
      phospholipids is developed. These lipids are used in formulations with egg-POPC
      and cholesterol to prepare light-sensitive liposomes. Irradiation of such
      liposomes in PBS buffer (medium pressure mercury lamp, Pyrex filter, lambda > 300
      nm) significantly increases the bilayer permeability and accelerates the release
      of entrapped small organic molecules by an order of magnitude. A simple assay,
      based on (1)H or (19)F PFG NMR measurements of diffusion coefficients, is
      developed to monitor light-induced unloading of the probe molecules.

PMID- 12010015
TI  - Are the carbon monoxide complexes of Cp(2)M (M = Ca, Eu, or Yb) carbon or oxygen
      bonded? An answer from DFT calculations.
AB  - DFT calculations have been performed on the CO adducts of the bivalent
      lanthanides, Cp(2)M(CO)(x), where M is Eu or Yb and x is 1 or 2, the alkaline
      earth metallocene Cp(2)Ca(CO), and the methylisocyanide adducts of Yb. The
      calculated nu(CO) values are in agreement with experiment for Cp(2)M(CO) when M
      is Ca or Eu, but in striking disagreement when the CO is bound to the metal by
      way of the carbon atom in CO in the case of Yb. The calculated nu(CO) values for
      M = Yb are brought into agreement with experiment when the CO is allowed to bond
      to Cp(2)Yb by way of the oxygen atom.

PMID- 12010016
TI  - Control of polymer topology through transition-metal catalysis: synthesis of
      hyperbranched polymers by cobalt-mediated free radical polymerization.
AB  - A novel approach was demonstrated for the synthesis of hyperbranched polymers by
      direct free radical polymerization of divinyl monomers controlled by a cobalt
      chain transfer catalyst (1). By controlling the competition between propagation
      and chain transfer with 1, the free radical polymerization of ethylene glycol
      dimethacrylate (3) afforded soluble hyperbranched polymers in one pot. The
      structure of the hyperbranched polymers was confirmed by (1)H and (13)C NMR. The
      molecular weight and intrinsic viscosity of the hyperbranched polymers were
      measured by matrix-assisted laser desorption ionization (MALDI) mass spectrometry
      and size exclusion chromatography (SEC) equipped with triple detectors. The
      intrinsic viscosities of the hyperbranched polymers are much lower than those of
      their linear analogues and do not show molecular weight dependence. The unique
      structure and properties of these hyperbranched polymers combined with the
      commercial availability of many divinyl monomers and the robustness of free
      radical polymerization make this new approach attractive for the preparation of
      new functional materials.

PMID- 12010017
TI  - A new approach to micropatterning: application of potential-assisted ion transfer
      at the liquid-liquid interface for the local metal deposition.
AB  - A new approach to micropatterning is demonstrated. The approach is based on
      driving an electrochemical process at the solid-liquid interface through the
      formation of a flux of ions from a micropipet that is held in close proximity to
      the surface. The flux of ions is generated by the so-called potential assisted
      ion transfer at the interface between two immiscible electrolyte solutions
      (ITIES). As a model system, the local deposition of silver was examined.
      Specifically, a constant potential, which was applied to a micropipet filled with
      an aqueous solution of silver ions, caused the transfer of Ag(+) into the outer
      nitrobenzene (NB) solution that consisted of an electrolyte, tetrabutylammonium
      tetrakis[4-chlorophenyl]borate (TBATPBCl). To facilitate the transfer of silver
      ions a macrocyclic ligand, that is, dibenzo-24-crown-8 (DB24C8), was added to the
      organic phase. The Faradaic current of this micro-ITIES was used as a means of
      controlling the tip-surface distance in scanning electrochemical microscopy
      (SECM) and depositing silver microstructures on a gold substrate.

PMID- 12010018
TI  - Novel arene receptors as nitric oxide (NO) sensors.
AB  - Nitric oxide sensors are based on the reversible, specific, and efficient binding
      to various types of arene receptors via intermolecular complexes, which are
      characterized by complete electron delocalization and strong interaction between
      the donor and acceptor moieties.

PMID- 12010019
TI  - Flexible inner and outer coordination of Zn(II) N-confused porphyrin complex.
AB  - Tetra- and dinuclear Zn(II) N-confused porphyrin dimers (1, 2) and pyridine
      coordinating Zn(II) monomer complex (3) were synthesized, and the ditopic, inner
      and outer coordination of Zn metal in the dimer complex (1) was demonstrated by X
      ray analyses.

PMID- 12010020
TI  - sigma-Borane and dihydroborate complexes of ruthenium.
AB  - Room temperature reaction of the bis(dihydrogen) complex
      RuH(2)(H(2))(2)(PCy(3))(2) (1) with excess pinacol borane (HBpin) generates the
      novel complex RuH[(mu-H)(2)Bpin](sigma-HBpin)(PCy(3))(2) (2) by loss of
      dihydrogen. Complex 2 was characterized spectroscopically and by X-ray
      crystallography. It contains two pinacolborane moieties coordinated in a
      different fashion, one as a dihydroborate (B-H distances : 1.58(3) and 1.47(3) A)
      and the other as a sigma-borane (B-H distance: 1.35(3) A). In addition, reaction
      of 1 with one equiv of HBpin yields total conversion to a new complex tentatively
      formulated as RuH[(mu-H)(2)Bpin](H(2))(PCy(3))(2) (3) on the basis of NMR data.
      In the presence of excess HBpin, 3 is converted to 2. Furthermore, under an
      atmosphere of dihydrogen, a C(7)D(8) solution of 2 rapidly converts to 3 and
      finally regenerates 1 over a much longer period. Thus, complex 3 is an
      intermediate in the formation of 2 from 1. In these processes the borane is
      eliminated as HBpin later hydrolyzed to BpinOBpin. Selective hydroboration of
      ethylene (3 bar) into C(2)H(5)Bpin is achieved using 1 or 2 as catalyst
      precursors in toluene, whereas in THF, competitive formation of the vinylborane
      C(2)H(3)Bpin (56% under 20 bar of C(2)H(4)) can be favored.

PMID- 12010021
TI  - Dicubyl disulfide.
AB  - Dicubyl disulfide (1) has been prepared in six steps from commercially available
      dimethyl-1,4-cubanedicarboxylate in 47% overall yield. In the final step, the
      previously unknown cubanethiol 2 was oxidized to disulfide 1. X-ray
      crystallography for 1 reveals the shortest tetragonal C-S bond on record (1.771
      A). In contrast to previous generalizations, density functional theory
      calculations predict a low S-S rotation barrier similar to that for t-BuSSBu-t.
      Low-temperature (13)C NMR (600 MHz) confirms the prediction.

PMID- 12010022
TI  - Lewis acid-base interactions between metal atoms and their applications for the
      synthesis of bimetallic cluster complexes.
AB  - A series of new palladium-ruthenium cluster complexes have been prepared by
      adding Pd(PBu(t)(3)) fragments to the ruthenium-ruthenium bonds of ruthenium
      carbonyl complexes. Reaction of Pd(PBu(t)(3))(2) with Ru(3)(CO)(12) yielded the
      tripalladium adduct Ru(3)(CO)(12)[Pd(PBu(t)(3))](3) 1. Compound 1 contains three
      Pd(PBu(t)(3)) groups symmetrically disposed with each one acting as a bridge
      across one Ru-Ru bond of the former Ru(3)(CO)(12) molecule. Reaction of
      Pd(PBu(t)(3))(2) with Ru(6)(CO)(17)(C) yielded the dipalladium adduct
      Ru(6)(CO)(17)(C)[Pd(PBu(t)(3))](2) 2. Compound 2 exists as two isomers in the
      solid state. One isomer has Pd(PBu(t)(3)) groups bridging two edges of the Ru(6)
      octahedron. The other isomer has a Pd(PBu(t)(3)) group bridging one edge of the
      Ru(6) octahedron, and the other is a triple bridge. The reaction of
      Pd(PBu(t)(3))(2) with Ru(CO)(5) yielded the dipalladium-diruthenium complex
      Ru(2)(CO)(9)[Pd(PBu(t)(3))](2) 3, a dipalladium adduct of the unstable molecule
      Ru(2)(CO)(9).

PMID- 12010023
TI  - Synthesis of seven-membered lactones via nickel- and zinc-catalyzed highly regio-
      and stereoselective cyclization of 2-iodobenzyl alcohols with propiolates.
AB  - A new class of substituted seven-membered lactones 3 were conveniently
      synthesized via cyclization of o-iodobenzyl alcohol 1 (o-IC(6)H(4)CH(2)OH) with
      various propiolates 2 (RC triple bond CCOOMe) in the presence of Ni(dppe)Br(2)
      and Zn powder in acetonitrile at 80 degrees C. The catalytic reaction is highly
      regio- and stereoselective affording seven-membered lactones in moderate to good
      yields. This methodology can be successfully extended to various substituted o
      iodobenzyl alcohols. An intermediate 7 was obtained from the reaction of 1a with
      methyl 2-octynoate (2a) in the presence of Ni(dppe)Br(2) and Zn at room
      temperature. A mechanism involving an unusual E/Z isomerization of the carbon
      carbon double bond of 7 prior to lactone formation is proposed to account for the
      catalytic reaction.

PMID- 12010024
TI  - Computational drug design accommodating receptor flexibility: the relaxed complex
      scheme.
AB  - A novel computational methodology for drug design that accommodates receptor
      flexibility is described. This "relaxed-complex" method recognizes that ligand
      may bind to conformations that occur only rarely in the dynamics of the receptor.
      We have shown that the ligand-enzyme binding modes are very sensitive to the
      enzyme conformations, and our approach is capable of finding the best ligand
      enzyme complexes. This new method serves as the computational analog of the
      experimental "SAR by NMR" and "tether" methods, which permit a building block
      approach for constructing a very potent drug.

PMID- 12010025
TI  - Seeking higher resolution and sensitivity for NMR of quadrupolar nuclei at
      ultrahigh magnetic fields.
AB  - We report the acquisition of solid-state NMR spectra of quadrupolar nuclei
      obtained at very high magnetic fields (25 and 40 T), thus improving spectral
      sensitivity and resolution. For an example compound, the MAS spectrum obtained at
      40 T is nearly free from the second-order quadrupolar broadening and can be
      interpreted quantitatively in a very simple manner.

PMID- 12010026
TI  - Neon matrix infrared spectrum of WH(6): a distorted trigonal prism structure.
AB  - Reactions of laser-ablated W atoms and H(2) molecules during condensation in
      excess neon give the WH, WH(2), WH(3), WH(4), and WH(6) hydride products. WH(6)
      absorptions increase on annealing to allow diffusion and further reaction of H(2)
      and decrease on photolysis such that six infrared bands can be grouped and
      assigned to WH(6). Excellent agreement between four observed neon matrix and four
      DFT calculated W-H stretching modes (two a(1) and two e) and bending and
      deformation modes (a(1) and e) confirms the present neon matrix preparation of
      WH(6) and the previous theoretical predictions of a distorted trigonal prism
      structure which is far from octahedral.

PMID- 12010027
TI  - Enantioselective direct-addition of terminal alkynes to imines catalyzed by
      copper(I)pybox complex in water and in toluene.
AB  - Highly enantioselective direct alkyne-imine additions catalyzed by Cu(I)OTf and
      Evan's pybox ligands were developed in water and in toluene. The process is
      simple and provides a diverse range of propargylic amine in high ee and good
      yield.

PMID- 12010028
TI  - The catalytic asymmetric Mannich-type reactions in aqueous media.
AB  - The catalytic, diastereo- and enantioselective Mannich-type reaction of a
      hydrazono ester with silyl enol ethers in aqueous media has been successfully
      achieved with ZnF(2), a chiral diamine ligand, and trifluoromethanesulfonic acid.

PMID- 12010029
TI  - High-efficiency fluorescence quenching of conjugated polymers by proteins.
AB  - The fluorescence of the water-soluble anionic conjugated polymer, poly[lithium 5
      methoxy-2-(4-sulfobutoxy)-1,4-phenylenevinylene] (MBL-PPV), is quenched in dilute
      aqueous solution by cytochrome c, a small, naturally occurring electron-transfer
      protein. The large value obtained for the Stern-Volmer constant (K(sv) = 3.2 x
      10(8) at pH 7.4, and approximately 10(9) in acidic solutions) is attributed to a
      combination of two factors: (1) facile ET between the luminescent semiconducting
      polymer and the protein and (2) the Columb attraction between the oppositely
      charged polyelectrolytes. This system shows significant potential for biosensor
      applications.

PMID- 12010030
TI  - Deliberate design of ligand architecture yields dramatic enhancement of metal ion
      affinity.
AB  - Evaluation of the malonamide substructure with respect to binding site
      preorganization and complementarity for lanthanide metal ions suggests a new
      ligand architecture specifically designed to enhance lanthanide ion affinity.
      Consideration of conformational reorganization, restricted bond rotation, and
      donor group orientation suggests that typical malonamide structures, for example,
      N,N,N'N'-tetrahexylpropane-1,3-diamide (1), N,N'-dibutyl-N,N'-dimethyl-2
      tetradecylpropane-1,3-diamide (2), or N,N,N'N'-tetramethylpropane-1,3-diamide
      (6), are poorly organized for metal ion complexation. Molecular mechanics
      analyses show that the unfavorable enthalpic and entropic terms are eliminated by
      the use of the novel bicyclic architecture found in 3,9-diaza-3,9
      dimethylbicyclo[4.4.0]decane-2,10-dione (7). Diamide 7 was prepared, and the X
      ray crystal structure of the complex [Eu(7)(2)(NO(3))(3)] exhibits the same
      chelate conformation predicted by the molecular mechanics model. A hydrophobic
      derivative, 3,9-diaza-3,9-dioctylbicyclo[4.4.0]decane-2,10-dione (8), was
      prepared, and solvent extraction studies reveal that the preorganized
      architecture of 8 gives a dramatic enhancement in binding affinity, exhibiting
      Eu(3+) distribution coefficients that are 7 orders of magnitude larger than a
      typical malonamide ligand, 1.

PMID- 12010031
TI  - The cobalt-catalyzed alternating copolymerization of epoxides and carbon
      monoxide: a novel approach to polyesters.
AB  - The metal-catalyzed synthesis of polyolefins, polyketones, and polycarbonates is
      well-known in academia and is already successfully applied in industrial
      processes. Still missing, however, is the metal-catalyzed synthesis of aliphatic
      polyesters, as one of the most important biodegradeable polymer families. We
      report here on the cobalt-catalyzed alternating copolymerization of propylene
      oxide and carbon monoxide, affording atactic and isotactic polyhydroxybutyrates
      (PHB). The postulated mechanism is supported by online ATR-IR analytics.

PMID- 12010032
TI  - Intein-mediated synthesis of geranylgeranylated Rab7 protein in vitro.
AB  - Production of recombinant proteins is an important prerequisite for biotechnology
      and life sciences in general. However, there is a paucity of methods for
      production of posttranslationally modified recombinant proteins or proteins with
      non-native functional groups, such as fluorophores, spin labels, and so forth. In
      this work we have used a combination of organic synthesis and in vitro protein
      ligation to construct monoprenylated Rab7 GTPase. The protein was prepared from a
      recombinant N-terminal portion and a peptide mimicking the C terminus of Rab7.
      For construction of a synthetic six-amino-acid-long fluorescent monoprenylated
      peptide, we used a block condensation strategy. Ligation was achieved with a
      yield of >70%. The resulting protein was purified from the unligated peptide by a
      combination of organic extraction and phase partitioning and refolding. The
      refolded monoprenylated semisynthetic Rab7 protein (Rab7GG) formed a stable
      complex with its natural chaperone REP-1 (Rab escort protein 1) and could serve
      as an acceptor of the second prenyl group in the enzymatic prenylation reaction.
      Using fluorescence spectroscopy, we characterized the interaction of the
      Rab7GG:REP-1 complex with Rab geranylgeranyl transferase and came to the
      conclusion that it functioned as a genuine intermediate of the prenylation
      reaction. Thus, we present the first example of the in vitro generation of a
      semisynthetic lipidated protein using the native chemical ligation method.

PMID- 12010033
TI  - Total synthesis and stereochemical assignment of the salicylate antitumor
      macrolide lobatamide C(1).
AB  - The total synthesis and stereochemical assignment of the potent antitumor
      macrolide lobatamide C is reported. The synthesis involves Cu(I)-mediated enamide
      formation and Na(2)CO(3)-mediated esterification of a beta-hydroxy acid and a
      salicylate cyanomethyl ester. Macrolactonization was accomplished using a
      Mitsunobu protocol. The stereochemical assignment of lobatamide C was achieved by
      Mosher ester analysis and comparison with prepared stereoisomers.

PMID- 12010034
TI  - A designed phenylalanyl-tRNA synthetase variant allows efficient in vivo
      incorporation of aryl ketone functionality into proteins.
AB  - Incorporation of non-natural amino acids into proteins in vivo expands the scope
      of protein synthesis and design. p-Acetylphenylalanine was incorporated into
      recombinant dihydrofolate reductase (DHFR) in Escherichia coli via a
      computationally designed mutant form of the phenylalanyl-tRNA synthetase of the
      host. DHFR outfitted with ketone functionality can be chemoselectively ligated
      with hydrazide reagents under mild conditions.

PMID- 12010035
TI  - Enantioselective total synthesis of callipeltoside A.
AB  - An asymmetric total synthesis of callipeltoside A has been accomplished
      highlighted by a catalytic enantioselective vinylogous aldol reaction and a boron
      mediated anti-aldol reaction influenced by remote stereocontrol.

PMID- 12010036
TI  - Direct catalytic asymmetric alpha-amination of aldehydes.
AB  - The first direct catalytic asymmetric alpha-amination of aldehydes is described
      herein. alpha-Unbranched aldehydes react in this novel proline-catalyzed reaction
      with dialkyl azodicarboxylates to give alpha-amino aldehydes in excellent yields
      and enantioselectivities.

PMID- 12010037
TI  - The first dirhodium tetracarboxylate molecule without axial ligation: new insight
      into the electronic structures of molecules with importance in catalysis and
      other reactions.
AB  - The first crystalline tetracarboxylato dirhodium paddlewheel complex with no
      axial ligation has been synthesized and structurally characterized. The compound,
      tetrakis(2,4,6-triisopropylbenzoato)dirhodium(II,II), Rh(2)(TiPB)(4), exhibits a
      Rh-Rh bond length of 2.3498(4) A. Interestingly, this is only ca. 0.02 A shorter
      than that in the corresponding bis-acetone adduct, 2.3700(4) A. The electronic
      spectrum exhibits two bands in the visible region; the low-energy band A has been
      previously attributed to a pi(Rh(2))-->sigma(Rh(2)) transition in various bis
      adducts. The spectrum of Rh(2)(TiPB)(4)(acetone)(2) shows this band at 610 nm,
      while that of Rh(2)(TiPB)(4) is greatly displaced to 760 nm. This is very
      persuasive evidence that the assignment for this transition is correct.

PMID- 12010038
TI  - Asymmetric total synthesis of spongistatins 1 and 2.
AB  - The total synthesis of spongistatin 1 (1) and spongistatin 2 (2) has been
      achieved through an advanced-stage intermediate. The synthesis is highlighted by
      a highly convergent assembly of the four key fragments (the C1-C15 AB fragment 2,
      the C16-C28 CD fragment 3, the C29-C43 EF fragment 4, and the C44-C51 side chain
      5) at a very advanced stage of the synthesis with minimal functional group
      interconversion. The CD fragment 3 functions as the central building block to
      which the other fragments are attached. The synthesis of the AB and CD spiroketal
      fragments is accomplished through the addition of a metalated gamma-pyrone to a
      beta-alkoxy aldehyde followed by spiroketalization. The EF subunit was assembled
      with high diastereoselectivity relying on asymmetric aldol reactions of
      chlorotitanium enolates of N-propionyl oxazolidinethiones and a double
      diastereoselective boron aldol to join the E and F fragments. Wittig coupling of
      the CD and EF fragments followed by a diastereoselective aldol reaction between
      the CDEF ketone and an AB aldehyde set the stage for attachment of the C44-C51
      side chains and final macrolactonization and deprotection.

PMID- 12010039
TI  - C-F...H-C hydrogen bonds in ribonucleic acids.
AB  - We report the synthesis of 1'-deoxy-1'-(benzimidazol-1-yl)-beta-D-ribofuranose 7
      and 1'-deoxy-1'-phenyl-beta-D-ribofuranose 2. With these two ribonucleoside
      analogues we have a set of nine different RNA building blocks in hand, which are
      isostere to the natural bases. Now it is possible to investigate their duplex
      stabilizing forces. These forces are hydrogen bonds, base stacking, and
      solvation. The phosphoramidites of all building blocks were incorporated into a
      12mer RNA, and the resulting RNA duplexes were investigated by UV- and CD
      spectroscopy. We found that some of the RNA analogues are universal bases. The
      best universal bases with the lowest destabilization and the smallest
      discrimination between the natural bases are 1 (B) and 9 (E). On the basis of UV
      measurements we determined the melting points and the thermodynamic data. We were
      able to show that there are no hydrogen bonds between the natural bases and the
      RNA analogues. From thermodynamic data we calculated the contributions for base
      stacking and solvation of all modified building blocks. Comparison of calculated
      and measured data of double modified base pairs in 12mer RNA duplexes showed a
      further duplex stabilizing force in base pairs containing fluorine atoms at the
      Watson-Crick binding site. This stabilizing force can be defined as C-F.H-C
      hydrogen bond as is observed in crystal structures of 1'-deoxy-1'-(4
      fluorophenyl)-beta-D-ribofuranose.

PMID- 12010040
TI  - Conformationally constrained macrocycles that mimic tripeptide beta-strands in
      water and aprotic solvents.
AB  - The beta-strand conformation is unknown for short peptides in aqueous solution,
      yet it is a fundamental building block in proteins and the crucial recognition
      motif for proteolytic enzymes that enable formation and turnover of all proteins.
      To create a generalized scaffold as a peptidomimetic that is pre-organized in a
      beta-strand, we individually synthesized a series of 15-22-membered macrocyclic
      analogues of tripeptides and analyzed their structures. Each cycle is highly
      constrained by two trans amide bonds and a planar aromatic ring with a short
      nonpeptidic linker between them. A measure of this ring strain is the restricted
      rotation of the component tyrosinyl aromatic ring (DeltaG(rot) 76.7 kJ mol(-1)
      (16-membered ring), 46.1 kJ mol(-1) (17-membered ring)) evidenced by variable
      temperature proton NMR spectra (DMF-d(7), 200-400 K). Unusually large amide
      coupling constants ((3)J(NH-CHalpha) 9-10 Hz) corresponding to large dihedral
      angles were detected in both protic and aprotic solvents for these macrocycles,
      consistent with a high degree of structure in solution. The temperature
      dependence of all amide NH chemical shifts (Deltadelta/T 7-12 ppb/deg) precluded
      the presence of transannular hydrogen bonds that define alternative turn
      structures. Whereas similar sized conventional cyclic peptides usually exist in
      solution as an equilibrium mixture of multiple conformers, these macrocycles
      adopt a well-defined beta-strand structure even in water as revealed by 2-D NMR
      spectral data and by a structure calculation for the smallest (15-membered) and
      most constrained macrocycle. Macrocycles that are sufficiently constrained to
      exclusively adopt a beta-strand-mimicking structure in water may be useful pre
      organized and generic templates for the design of compounds that interfere with
      beta-strand recognition in biology.

PMID- 12010041
TI  - Enhanced electron transfer and lauric acid hydroxylation by site-directed
      mutagenesis of CYP119.
AB  - CYP119, a cytochrome P450 from a thermophilic organism for which a crystal
      structure is available, is shown here to hydroxylate lauric acid in a reaction
      supported by putidaredoxin and putidaredoxin reductase. This fatty acid
      hydroxylation activity is increased 15-fold by T214V and D77R mutations. The
      T214V mutation increases the rate by facilitating substrate binding and enhancing
      the associated spin state change, whereas the D77R mutation improves binding of
      the heterologous redox partner putidaredoxin to CYP119 and the rate of electron
      transfer from it to the heme group. A sequence alignment with P450(cam) can,
      therefore, be used to identify a part of the binding site for putidaredoxin on an
      unrelated P450 enzyme. This information can be used to engineer by mutagenesis an
      improved complementarity of the protein-protein interface that results in
      improved electron transfer from putidaredoxin to the P450 enzyme. As a result,
      the catalytic activity of the thermo- and barostable CYP119 has been incorporated
      into a catalytic system that hydroxylates fatty acids.

PMID- 12010042
TI  - Amplification of screening sensitivity through selective destruction: theory and
      screening of a library of carbonic anhydrase inhibitors.
AB  - A new method for identifying enzyme inhibitors is to conduct their synthesis in
      the presence of the targeted enzyme. Good inhibitors form in larger amounts than
      poorer ones because the binding either speeds up synthesis (target-accelerated
      synthesis) or shifts the synthesis equilibrium (dynamic combinatorial libraries).
      Several groups have successfully demonstrated this approach with simple systems,
      but application to larger libraries is challenging because of the need to
      accurately measure the amount of each inhibitor. In this report, we dramatically
      simplify this analysis by adding a reaction that destroys the unbound inhibitors.
      This works similar to a kinetic resolution, with the best inhibitor being the
      last one remaining. We demonstrate this method for a static library of several
      sulfonamide inhibitors of carbonic anhydrase. Four sulfonamide-containing
      dipeptides, EtOC-Phe(sa)-Phe (4a), EtOC-Phe(sa)-Gly (4b), EtOC-Phe(sa)-Leu (4c)
      and EtOC-Phe(sa)-Pro (4d), were prepared and their inhibition constants measured.
      These inhibitors migrated to the carbonic anhydrase compartment of a two
      compartment vessel. Although higher concentrations of the better inhibitors were
      observed in the carbonic anhydrase compartment, the concentration differences
      were small (1.83:1.71:1.54:1.46:1 for 4a:4b:4c:4d:5, where 5 is a noninhibiting
      dipeptide EtOC-Phe-Phe). Addition of a protease rapidly cleaved the weaker
      inhibitors (4d and 5). Intermediate inhibitor 4c was cleaved at a slower rate,
      and at the end of the reaction, only 4a and 4b remained. In a separate
      experiment, the ratio of 4a to 4b was found to increase over time to a final
      ratio of nearly 4:1. This is greater than the ratio of their inhibition constants
      (approximately 2:1). The theoretical model predicts that these ratios would
      increase even further as the destruction proceeds. This removal of poorer
      inhibitors simplifies identification of the best inhibitor in a complex mixture.

PMID- 12010043
TI  - Electron-transfer mechanisms through biological redox chains in multicenter
      enzymes.
AB  - A new approach for studying intramolecular electron transfer in multicenter
      enzymes is described. Two fumarate reductases, adsorbed on an electrode in a
      fully active state, have been studied using square-wave voltammetry as a kinetic
      method to probe the mechanism of the long-range electron transfer to and from the
      buried active site. Flavocytochrome c(3) (Fcc(3)), the globular fumarate
      reductase from Shewanella frigidimarina, and the soluble subcomplex of the
      membrane-bound fumarate reductase of Escherichia coli (FrdAB) each contain an
      active site FAD that is redox-connected to the surface by a chain of hemes or Fe
      S clusters, respectively. Using square-wave voltammetry with large amplitudes, we
      have measured the electron-transfer kinetics of the FAD cofactor as a function of
      overpotential. The results were modeled in terms of the FAD group receiving or
      donating electrons either via a direct mechanism or one involving hopping via the
      redox chain. The FrdAB kinetics could be described by both models, while the
      Fcc(3) data could only be fit on the basis of a direct electron-transfer
      mechanism. This raises the likelihood that electron transfer can occur via a
      superexchange mechanism utilizing the heme groups to enhance electronic coupling.
      Finally, the FrdAB data show, in contrast to Fcc(3), that the maximum ET rate at
      high overpotential is related to the turnover number for FrdAB measured
      previously so that electron transfer is the limiting step during catalysis.

PMID- 12010044
TI  - Measurement of side-chain carboxyl pK(a) values of glutamate and aspartate
      residues in an unfolded protein by multinuclear NMR spectroscopy.
AB  - A triple-resonance NMR pulse scheme is presented for measuring aspartic and
      glutamic acid side-chain pK(a) values in unfolded protein states where chemical
      shift overlap is limiting. The experiment correlates side-chain carboxyl carbon
      chemical shifts of these residues with the backbone amide proton chemical shift
      of the following residue. The methodology is applied to an (15)N, (13)C labeled
      sample of the N-terminal SH3 domain of the Drosophila protein drk, which exists
      in equilibrium between folded (F(exch)) and unfolded (U(exch)) states under
      nondenaturing conditions. Residue-specific pK(a) values of side-chain carboxyl
      groups are presented for the first time for an unfolded protein (drk U(exch)
      state), determined from a pH titration. Results indicate that deviations from
      pK(a) values measured for model compounds are likely due to local effects, while
      long-range electrostatic interactions appear to be of minor importance for this
      protein.

PMID- 12010045
TI  - Novel chemistry of alpha-tosyloxy ketones: applications to the solution- and
      solid-phase synthesis of privileged heterocycle and enediyne libraries.
AB  - New synthetic technologies for the preparation and elaboration of alpha-tosyloxy
      ketones in solution- and on solid-phase are described. Both olefins and ketones
      serve as precursors to these relatively stable chemical entities: olefins via a
      novel one-pot epoxidation, arylsulfonic acid displacement, and oxidation
      sequence, and ketones by direct exposure to arylsulfonic acids in the presence of
      diacetoxy iodobenzene. Reaction of these substrates with O-, S-, or N-centered
      nucleophiles leads to incorporation of the nucleophile with concomitant expulsion
      of the sulfonate, while exposure to bis-functional nucleophiles furnishes
      annulated heterocyclic systems. In addition, the reactions of carbon-centered
      nucleophiles with alpha-tosylyloxy ketones are also explored. The collated data
      for all these nucleophiles provide compelling evidence for the proposal that
      different reaction pathways are followed when alpha-tosyloxy ketones are engaged
      by "hard" versus "soft" nucleophiles. The accessibility and site-selectivity of
      the chemistry demonstrated herein offer the promise of an expanded use for this
      moiety in solid-phase library construction, in particular, and in the field of
      organic synthesis, in general.

PMID- 12010046
TI  - Preparation of cadmium selenide-polyolefin composites from functional phosphine
      oxides and ruthenium-based metathesis.
AB  - Cadmium selenide nanoparticles, prepared by known methods, were stabilized with
      functional phosphine oxide 1, then used to support the polymerization of cyclic
      olefins radially outward from the surface by ruthenium-catalyzed ring-opening
      metathesis polymerization (ROMP). The conversion of compound 1 into the new
      metathesis catalyst 3 by carbene exchange and the subsequent polymerization of
      cyclic olefins were observed spectroscopically by (1)H NMR to afford for example
      CdSe-polycyclooctene composite 6. Transmission electron micrographs on thin films
      of these composites showed good nanoparticle dispersion. This is in stark
      contrast to the substantial nanoparticle aggregation observed when similar
      polymerizations were performed in the presence of conventional TOPO-covered
      nanoparticles. The methods reported here to prepare composite product 6 are
      applicable to other cyclic olefins, and suggest that this chemistry will be
      useful for incorporating CdSe nanoparticles into a wide variety of polymer
      matrices.

PMID- 12010047
TI  - An insight into the aromaticity of fullerene anions: experimental evidence for
      diamagnetic ring currents in the five-membered rings of C(60)(6-) and C(70)(6-).
AB  - Reduction of the two "closed" [6,6] methanofullerenes, [6,6]C(61)H(2) (1) and
      [6,6]C(71)H(2) (5), to the corresponding hexaanions with lithium metal causes the
      bridgehead-bridgehead bonds to open, at least partially, and this change gives
      rise to diamagnetic ring currents in the resulting homoconjugated six-membered
      rings (6-MRs). These new ring currents shield the overlying hydrogen atoms on the
      methylene bridge and induce upfield shifts of 1.60 and 0.11 ppm in their (1)H NMR
      resonances, respectively. Analogous reduction of the already "open"
      [5,6]methanofullerenes, [5,6]C(61)H(2) (2) and [5,6]C(71)H(2) (3 and 4), only
      slightly enhances the shielding of the hydrogen atoms over the homoconjugated 6
      MRs (upfield shifts of 0.13, 0.68, and 0.14 ppm, respectively) but leads to
      exceptionally strong diamagnetic ring currents in the homoconjugated five-
      membered rings (5-MRs), as evidenced by dramatic shielding of the hydrogen atoms
      situated over them (upfield shift of 5.01, 6.78, and 1.63 ppm, respectively). The
      strongest shielding is seen for the hydrogen atom sitting over the 5-MR at the
      pole of C(71)H(2)(6)(-) (delta = -0.255 ppm) indicating that the excess charge
      density is concentrated at the poles.

PMID- 12010048
TI  - Efficient chemoenzymatic synthesis of O-linked sialyl oligosaccharides.
AB  - The tumor associated Tn (GalNAcalpha(1-1)-Thr/Ser)- and T (Galbeta(1-3)
      GalNAcalpha(1-1)Thr/Ser)-antigens and their sialylated derivatives are present on
      the surface of many cancer cells. Preparative synthesis of these sialylated T-
      and Tn-structures has been achieved mainly from a chemical synthetic approach due
      to the lack of the required glycosyltransferases. We demonstrate a flexible and
      efficient chemoenzymatic approach for using recombinant sialyltransferases
      including a chicken GalNAcalpha2,6-sialyltransferase (chST6GalNAc I) and a
      porcine Galbeta(1-3)GalNAcalpha-2,3-sialyltransferase (pST3Gal I). Using these
      enzymes, the common O-linked sialosides Neu5Acalpha(2-6)GalNAcalpha(1-1)Thr,
      Galbeta(1-3)[Neu5Acalpha(2-6)]GalNAcalpha(1-1)Thr, Neu5Acalpha(2-3)Galbeta(1
      3)GalNAcalpha(1-1)Thr, and Neu5Acalpha(2-3)Galbeta(1-3)[Neu5Acalpha(2
      6)]GalNAcalpha(1-1)Thr were readily prepared at preparative scale. The
      chST6GalNAc I was found to require at least one amino acid (Thr/Ser) for optimal
      activity, and is thus an ideal catalyst for synthesis of synthetic glycopeptides
      and glycoconjugates with O-linked glycans.

PMID- 12010049
TI  - Unraveling the mechanism of epoxide formation from sulfur ylides and aldehydes.
AB  - Sulfur ylides R(2)S(+)-C(-)HR' react with aldehydes R' '-CHO to form epoxides,
      predominantly as the trans isomers, in a synthetically useful reaction which is
      increasingly used in its asymmetric variant with chiral sulfides. The mechanisms
      of the "model" reaction (R = Me, R' = R' ' = H) and the reaction forming stilbene
      oxide (R = Me, R' = R' ' = Ph) have been studied in detail using density
      functional theory, the B3LYP density functional, and flexible basis sets. It has
      been shown that for this reaction involving highly polar intermediates, continuum
      solvation models need to be used throughout to obtain reasonable results. For the
      reaction of benzaldehyde with dimethylsulfonium benzylide, the key steps are
      shown to be quasi [2 + 2] addition of the ylide to the aldehyde to form a betaine
      R'-CH(S(+)Me(2))-CH(O(-))-R' ' in which the charged groups are gauche to one
      another, and torsional rotation around the C-C single bond of the betaine to form
      its rotamer with the two charged groups anti. The final step, elimination of
      sulfide from this second rotamer of the betaine, is found to be facile. In the
      case of the anti pathway, leading to trans-stilbene epoxide, the initial addition
      is found to be rate-determining, whereas for the diastereomeric syn pathway,
      leading to the cis-epoxide, it is instead the torsional rotation which is
      slowest. These results are in excellent agreement with experiment, unlike
      previous computational work. The unexpected and apparently unprecedented (for C-C
      bond-forming reactions) importance of the torsional rotation step, especially in
      the syn case, is due to the fact that all the barriers involved are low-lying.
      This novel picture of the mechanism provides a sound basis for the future
      development of chiral sulfides for enantioselective epoxide synthesis.

PMID- 12010050
TI  - Basicity of a stable carbene, 1,3-di-tert-butylimidazol-2-ylidene, in THF.
AB  - The basicity of 1,3-di-tert-butylimidazol-2-ylidene (1) was measured in THF
      against three hydrocarbon indicators. Both ion pairs and free ions were found and
      the corresponding equilibrium constants were measured. Homoconjugation was not
      found in either THF or DMSO. The carbene is effectively more basic in DMSO by
      several pK units, probably because of hydrogen bonding of 1-H(+) to DMSO. Model
      ab initio computations are consistent with these results.

PMID- 12010051
TI  - Dendron rodcoils: synthesis of novel organic hybrid structures.
AB  - Convergent and divergent syntheses of novel organic hybrid structures termed
      dendron rodcoils (DRC) containing dendritic, rodlike, and coillike segments are
      described. The aryl ester dendron masked with 32 trifluoromethyl groups is
      prepared via a convergent approach using 5-(tert-butyldimethylsiloxy)isophthalic
      acid as the monomer unit. The activation of the focal point of the dendron allows
      for successful coupling between the dendron and the diblock rodcoil molecules
      synthesized separately. In another example, the dendritic block is grown via
      divergent strategy from the terminus of rodcoil using 3,5-bis(tert
      butyldimethylsiloxy)benzoic acid as an AB(2) monomer. A combination of catalyzed
      esterification reactions and silyl deprotection chemistry proved to be a very
      efficient method for construction of these nanosized structures with unusual
      molecular architecture. Both synthetic strategies allowed for the preparation of
      DRCs with nearly monodisperse dendritic blocks as demonstrated by NMR, MALDI-TOF,
      and GPC measurements.

PMID- 12010052
TI  - Quasiracemic synthesis: concepts and implementation with a fluorous tagging
      strategy to make both enantiomers of pyridovericin and mappicine.
AB  - The concept of quasiracemic synthesis is introduced and illustrated with
      syntheses of both enantiomers of pyridovericin (whose absolute configuration is
      assigned as R) and mappicine. Like racemic synthesis, quasiracemic synthesis
      provides both enantiomers in a single synthetic sequence; however, separation
      tagging is used to ensure that quasiracemic mixtures can be analyzed, separated,
      and identified on demand. Fluorous tags of differing chain lengths are used to
      tag two enantiomeric starting materials. The resulting quasienantiomers are mixed
      to make a quasiracemate, which is then treated like a true racemate in successive
      steps of the synthesis. Fluorous chromatography is used to separate, or demix,
      the final quasiracemate into its two components, which are then detagged to
      provide (true) enantiomeric products. Quasiracemic synthesis is portrayed as the
      first and simplest of a series of mixture synthesis techniques based on
      separation tagging, and the prospects for using other types of separation tags
      are briefly evaluated.

PMID- 12010053
TI  - Dynamic distribution of growth rates within the ensembles of colloidal II-VI and
      III-V semiconductor nanocrystals as a factor governing their photoluminescence
      efficiency.
AB  - The distribution of properties within ensembles of colloidally grown II-VI and
      III-V semiconductor nanocrystals was studied. A drastic difference in the
      photoluminescence efficiencies of size-selected fractions was observed for both
      organometallically prepared CdSe and InAs colloids and for CdTe nanocrystals
      synthesized in aqueous medium, indicating a general character of the phenomenon
      observed. The difference in the photoluminescence efficiencies is attributed to
      different averaged surface disorder of the nanocrystals originating from the
      Ostwald ripening growth mechanism when larger particles in the ensemble grow at
      the expense of dissolving smaller particles. At any stage of growth, only a
      fraction of particles within the ensemble of growing colloidal nanocrystals has
      the most perfect surface and, thus, shows the most efficient photoluminescence.
      This is explained by a theoretical model describing the evolution of an ensemble
      of nanocrystals in a colloidal solution. In an ensemble of growing nanocrystals,
      the fraction of particles with the highest photoluminescence corresponds to the
      particle size having nearly zero average growth rate. The small average growth
      rate leads to the lowest possible degree of surface disorder at any given
      reaction conditions.

PMID- 12010054
TI  - Crystal chemistry of the gold (I) trimer, Au(3)(NC(5)H(4))(3): formation of
      hourglass figures and self-association through aurophilic attraction.
AB  - X-ray crystallography reveals that individual molecules of Au(3)(NC(5)H(4))(3)
      self-associate through aurophilic interactions into two distinct structural
      motifs that involve both extended chains of molecules connected by pairwise Au.Au
      contacts and individual Au.Au contacts and discrete dimers linked by pairwise
      Au.Au contacts. The colorless or pale yellow crystals are remarkable for the
      formation of a distinct hourglass shape within the crystals that develops after
      months of standing in the atmosphere or after immersion in 4 M hydrochloric acid
      for a few days. The hourglass figures appear to result from the deposition of
      gold and are unusual in being formed by a chemical reaction within a crystal
      rather than as a result of dying the crystal during growth.

PMID- 12010055
TI  - Nanocluster formation and stabilization fundamental studies: ranking commonly
      employed anionic stabilizers via the development, then application, of five
      comparative criteria.
AB  - To start, a brief introduction is provided on the importance of transition-metal
      nanoclusters, on the need to develop and then apply methods to rank the
      nanocluster formation and then stabilizing abilities of commonly employed anions,
      solvents, cations, and polymers, and on the somewhat confused literature of
      nanocluster stabilization. The fundamental importance of surface-adsorbed anions
      in transition-metal nanocluster stabilization is noted, the reason the present
      studies begin with a study of nanocluster-stabilizing anions. Next, five
      criteria, as well as the associated experimental methods, are developed to
      evaluate the efficacy of nanocluster stabilizing agents. The criteria are of
      fundamental significance in that they allow the separation of stabilizing agent
      effects on nanocluster formation from those on nanocluster stabilization. The
      results from applying the five criteria to four commonly employed anions lead to
      the first "anion series" of relative nanocluster-formation and stabilizing
      abilities, at least for the Ir(0) nanoclusters examined and by the following five
      criteria: [(P(2)W(15)Nb(3)O(61))(2)O](16-) (a Brphinsted-basic polyoxoanion) >
      C(6)H(5)O(7)(3-) (citrate trianion) > [-CH(2)-CH(CO(2))-](n)(n-) (polyacrylate)
      approximately Cl(-). In addition to the needed methods and the first anion
      series, six other (8 total) conclusions are reached, important insights in an
      area previously lacking hard information about which anions are the better
      choices for nanocluster formation and stabilization. The results are also of
      significance in establishing polyoxoanions, notably highly charged and basic
      polyoxoanions such as [(P(2)W(15)Nb(3)O(61))(2)O](16)(-), as the present "Gold
      Standards" among currently known nanocluster stabilizing anions, and according to
      the above five criteria. Such standards provide a reference point for future work
      aspiring to develop even better nanocluster stabilizing anions, solvents,
      cations, and polymers or their combinations.

PMID- 12010056
TI  - Synthesis and properties of water-soluble gold colloids covalently derivatized
      with neutral polymer monolayers.
AB  - Citrate-capped gold nanoparticles as well as planar gold surfaces can be
      efficiently grafted with a covalently attached polymer monolayer a few nanometers
      thick, by simple contact of the metal surface with dilute aqueous solutions of
      hydrophilic polymers that are end-capped with disulfide moieties, as shown by
      UV/vis absorption, dynamic light scattering, and surface plasmon resonance
      studies. The hydrophilic polymer-coated gold colloids can be freeze-dried and
      stored as powders that can be subsequently dissolved to yield stable aqueous
      dispersions, even at very large concentrations. They allow for applying
      filtrations, gel permeation chromatography, or centrifugation. They do not suffer
      from undesirable nonspecific adsorption of proteins while allowing the diffusion
      of small species within the hydrogel surface coating. In addition, specific
      properties of the original hydrophilic polymers are retained such as a lower
      critical solution temperature. The latter feature could be useful to enhance
      optical responses of functionalized gold surfaces toward interaction with various
      substrates.

PMID- 12010057
TI  - Model-free analysis of protein backbone motion from residual dipolar couplings.
AB  - On the basis of the measurement of NH residual dipolar couplings (RDCs) in 11
      different alignment media, an RDC-based order parameter is derived for each
      residue in the protein ubiquitin. Dipolar couplings are motionally averaged in
      the picosecond to millisecond time range and, therefore, reflect motion slower
      than the inverse overall tumbling correlation time of the protein. It is found
      that there is considerable motion that is slower than the correlation time and
      could not be detected with previous NMR methodology. Amplitudes and anisotropies
      of the motion can be derived from the model-free analysis. The method can be
      applied provided that at least five sufficiently different alignment media can be
      found for the biomolecule under investigation.

PMID- 12010058
TI  - On the competition of the purine bases, functionalities of peptide side chains,
      and protecting agents for the coordination sites of dicationic cisplatin
      derivatives.
AB  - The Pt-L bond energies of simple triammineplatinum(II) complexes,
      [Pt(NH(3))(3)L](2+), with oxygen-, nitrogen-, and sulfur-containing donor ligands
      L have been predicted and rationalized using density functional theory. The
      ligands L have been chosen as models for functionalities of peptide side chains,
      for sulfur-containing protecting agents, and for adenine and guanine sites of the
      DNA as the ultimate target of platinum anticancer drugs. Calculation of the Pt-L
      bond energy in [Pt(NH(3))(3)L](2+) reveals that the soft metal center of
      triammineplatinum(II) prefers N ligands over S ligands. This remarkable result
      has been discussed in light of several interpretations of the hard and soft acids
      and bases principle. The concept of orbital-symmetry-based energy decomposition
      has been employed for the determination of the contributions from sigma and pi
      orbital interactions, electrostatics, and intramolecular hydrogen bonding to the
      Pt-L bond energy. The calculations show that considerable differences in the bond
      energies of the triammineplatinum(II) complexes with N-heterocycles such as 1
      methylimidazole, 9-methyladenine, and 9-methylguanine arise from electrostatics
      rather than from orbital interactions. Surprisingly, the net stabilization by
      hydrogen bonding between the (Pt)N-H group and the oxygen of 9-methylguanine is
      as weak as the intramolecular hydrogen bond in the aqua complex
      [Pt(NH(3))(3)(H(2)O)](2+), challenging the common hypothesis that DNA-active
      anticancer drugs require carrier ligands with N-H functionalities because of
      their hydrogen-bonding ability. The influence of a polarizable environment on the
      stability of the complexes has been investigated systematically with the
      dependence of the dielectric constant epsilon. With increasing epsilon, the
      complexes with S-containing ligands are more strongly stabilized than the
      complexes of the N-containing heterocycles. At epsilon = 78.4, the dielectric
      constant of water, 9-methylguanine remains the only purine derivative
      investigated which is competitive to neutral sulfur ligands. These findings are
      particularly important for a rationalization of the results from recent
      experimental studies on the competition of biological donor ligands L for
      coordination with the metal center of [Pt(dien)L](2+) (dien = 1,5-diamino 3
      azapentane).

PMID- 12010059
TI  - Dissociation kinetics of energy-selected Cp(2)Mn(+) ions studied by threshold
      photoelectron-photoion coincidence spectroscopy.
AB  - Threshold photoelectron-photoion coincidence spectroscopy has been used to
      investigate the dissociation kinetics of the manganocene ion, Cp(2)Mn(+) (Cp =
      eta(5)-cyclopentadienyl). The Cp loss reaction was found to be extremely slow
      over a large ion internal energy range. By simulating the measured asymmetric
      time-of-flight peak shapes and breakdown diagram, the 0 K thermochemical
      dissociation limit for CpMn(+) production was determined to be 9.55 +/- 0.15 eV.
      A CpMn(+)-Cp bond energy of 3.43 eV was obtained by combining this CpMn(+) + Cp
      dissociation limit with the Cp(2)Mn adiabatic ionization energy of 6.12 +/- 0.07
      eV. Combining the measured onset with known heats of formation of Cp and Mn(+),
      the Cp-Mn(+) bond energy was determined to be 3.38 +/- 0.15 eV. These results
      lead to 298 K heats of formation of Cp(2)Mn(+) and CpMn(+) of 863 +/- 7 and 935
      +/- 16 kJ/mol, respectively. Finally, by combining these results with a previous
      measurement of the CpMn(CO)(3) --> CpMn(+) + 3CO + e(-) dissociation limit, we
      arrive at a new value for Delta(f)H degrees (298K)(CpMn(CO)(3)) of -424 +/- 17
      kJ/mol.

PMID- 12010060
TI  - Solid-state (67)zn NMR spectroscopy in bioinorganic chemistry. Spectra of four-
      and six-coordinate zinc pyrazolylborate complexes obtained by management of
      proton relaxation rates with a paramagnetic dopant.
AB  - Solid-state (67)Zn NMR spectra of model compounds for metalloproteins, such as
      [H(2)B(3,5-Me(2)pz)(2)](2)Zn (pz denotes pyrazolyl ring), have been obtained
      using low temperatures (10 K) to enhance the Boltzmann factor in combination with
      cross polarization (CP) from (1)H to (67)Zn. Attempts to observe spectra of other
      model compounds, such as [H(2)B(pz)(2)](2)Zn, were hindered by long relaxation
      times of the protons. To decrease the proton relaxation times, the high-spin six
      coordinate complex [HB(3,4,5-Me(3)pz)(3)](2)Fe has been investigated as a dopant.
      NMR and EPR measurements have shown that this Fe(II) dopant effectively reduces
      the (1)H spin lattice relaxation time, T(1), of the zinc samples in the
      temperature range 5-10 K with minimal perturbations of the (1)H spin lattice
      relaxation time in the rotating frame, T(1)(rho). Using this methodology, we have
      determined the (67)Zn NMR parameters of four- and six-coordinate zinc(II)
      poly(pyrazolyl)borate complexes that are useful models for systems of biological
      importance. The (67)Zn NMR parameters are contrasted to the corresponding changes
      in the (113)Cd NMR parameters for the analogous compounds. Further, these
      investigations have demonstrated that a temperature-dependent phase transition
      occurs in the neighborhood of 185 K for [HB(3,5-Me(2)pz)(3)](2)Zn; the other
      poly(pyrazolyl)borate complexes we investigated did not show this temperature
      dependent behavior. This conclusion is confirmed by a combination of room
      temperature high-field (18.8 T) solid-state (67)Zn NMR spectroscopy and low
      temperature X-ray methods. The utilization of paramagnetic dopants should enable
      low-temperature cross polarization experiments to be performed on a wide variety
      of nuclides that are important in bioinorganic chemistry, for example, (25)Mg,
      (43)Ca, and (67)Zn.

PMID- 12010061
TI  - What is the nature of polyacetylene neutral and anionic chains HC(2n)H and
      HC(2n)H(-) (n = 6-12) that have recently been observed?
AB  - The optimized geometries, adiabatic electron affinities, and IR-active
      vibrational frequencies have been predicted for the long linear carbon chains
      HC(2n)H. The B3LYP density functional combined with the DZP basis set was used in
      this theoretical study. The computed physical properties are discussed. The
      predicted electron affinities form a remarkably regular sequence: 1.78 (HC(12)H),
      2.08 (HC(14)H), 2.32 (HC(16)H), 2.53 (HC(18)H), 2.69 (HC(20)H), 2.83 (HC(22)H),
      and 2.95 eV (HC(24)H). The predicted structures display an alternating triple and
      very short single bond pattern, with the degree of bond alternation significantly
      less for the radical anions.

PMID- 12010062
TI  - Electron delocalization in acyclic and N-heterocyclic carbenes and their
      complexes: a combined experimental and theoretical charge-density study.
AB  - Combined experimental and theoretical charge-density studies on free and metal
      coordinated N-heterocyclic carbenes have been performed to investigate the extent
      of electron delocalization in these remarkable species. Tracing the orientation
      of the major axis of the bond ellipticity (the least negative curvature in the
      electron density distribution) along the complete bond paths distinguishes
      unambiguously between fully delocalized systems and those with interrupted cyclic
      electron delocalization. Evaluation of charge-density-based properties such as
      atomic quadrupole moments serves as a direct and quantitative measure of the
      extent of pi-electron delocalization and reveals consistency between theory and
      experiment. A detailed topological analysis of theoretical charge densities for
      two benchmark carbene systems, viz., 1,2-dimethylpyrazol-3-ylidene 1a and 1,3
      dimethylimidazol-2-ylidene 2a, and their corresponding stable chromium
      pentacarbonyl complexes 1 and 2, highlights the advantages of charge-density
      based criteria to analyze such complex electronic situations. Thus, 1a and 2a
      display a different extent of electron delocalization; yet nearly identical p(pi)
      occupations at the carbene center are computed for 1a and 2a. However, atomic
      quadrupoles Q(zz) - the charge-density analogues of p(pi) occupation - reveal
      faithfully the electronic differences in 1a and 2a and demonstrate the
      sensitivity of charge-density-based properties to the bonding situation. The
      acyclic aminocarbene (iPr(2)N)(2)CCr(CO)(4) has also been studied, and the high
      barrier to rotation about the C-N bond is shown not to arise solely from p(pi)
      p(pi) bonding.

PMID- 12010063
TI  - How to detect internal motion by homonuclear NMR.
AB  - NOESY and ROESY cross-peak intensities depend on internuclear distances and
      internal motion. Internal motion is usually ignored, and NOESY cross-peak
      intensities are interpreted in terms of internuclear distances only. Off
      resonance ROESY experiments measure a weighted average of NOE and ROE. The weight
      can be described and experimentally set by an angle theta;. For large enough
      molecules, NOE and ROE have opposite signs. Therefore, each cross-peak intensity
      becomes zero for an angle theta;(0). For any sample, the maximum angle theta;(0)
      is determined by the overall motion of the molecule. Smaller theta;(0) values
      reflect the angular component of internal motions. Because individual cross-peaks
      are analyzed, the method evaluates internal motions of individual H,H vectors.
      The reduction of theta;(0) is largest for internal motions on a time scale of 100
      300 ps. The sensitivity of theta;(0) for internal motions decreases with
      increasing molecular weight. We estimate that detecting internal motions will be
      practicable for molecules up to about 15 kDa. We describe a protocol to measure
      theta;(0) from a series of off-resonance ROESY spectra. For such a series, we
      describe the choice of experimental parameters, a procedure to extract theta;(0)
      from the raw data, and the interpretation of theta;(0) in terms of internal
      motions. In the small protein BPTI, we analyzed 75 cross-peaks. The precision of
      theta;(0) was 0.25 degrees, as compared to typical reductions of theta;(0) of 3
      degrees. We found a well-defined maximum theta;(0) for cross-peaks in rigid parts
      of the molecule, which reflects the overall motion of the molecule. For BPTI,
      also many structurally important long-range cross-peaks appear rigid. The lower
      theta;(0) values of long-range contacts involving methyl groups are consistent
      with methyl rotation on the 25-ps time scale. The lower theta;(0) values of the
      flexible C-terminus and of flexible side chains translate into upper limits for
      the angular order parameter of 0.4 and 0.5-0.8, respectively. Off-resonance ROESY
      can monitor internal motions of H,H contacts that are used in a structure
      calculation. Because no isotope labeling is needed, off-resonance ROESY can be
      used to detect internal motions in a wide range of natural products.

PMID- 12010064
TI  - A structural model for the high-valent intermediate Q of methane monooxygenase
      from broken-symmetry density functional and electrostatics calculations.
AB  - A combined broken-symmetry density functional and electrostatics approach has
      been used to construct a model for the high-valent diiron intermediate Q of
      methane monooxygenase. The presence of high-spin or intermediate spin iron
      centers gives rise to two structurally distinct spin-coupled states of the
      cluster for which calculated geometries, net spin populations, Heisenberg J
      values, Mossbauer isomer shifts, and quadrupole splittings are compared and
      contrasted with the available spectroscopic data.

PMID- 12010065
TI  - The first precise molecular structure of a monomeric transition metal cyanide,
      copper(I) cyanide.
AB  - Copper(I) cyanide is an important reagent in organic, organometallic, and
      supramolecular chemistry because of both the copper center and the versatile
      cyanide ligand. Solid-phase CuCN and many of its derivatives show oligomeric or
      polymeric structures, a trait shared by other metal cyanides. Often, it is
      difficult to specify the orientation of the cyano ligand in an X-ray structure.
      Here the first preparation and precise structure of a monomeric transition metal
      cyanide is reported. Gas-phase reaction between copper vapor and cyanogen (NCCN)
      clearly gives CuCN (not CuNC). The precise structure of CuCN so produced is
      determined by millimeter/submillimeter-wave spectroscopy. Because of the highly
      efficient synthesis and the presence of significant amounts of two copper
      isotopes, such strong signals were seen that natural-abundance materials allowed
      observation of transitions for the four isotopomers (63)Cu(12)C(14)N,
      (65)Cu(12)C(14)N, (63)Cu(13)C(14)N, and (63)Cu(12)C(15)N and the determination of
      r(o), r(s), and r(m)((2)) structures. All data unequivocally show a linear
      geometry and that the carbon of cyanide is bound to copper with a Cu-C distance
      of 1.82962(4) A in the r(m)((2)) structure, which is likely to be closest to the
      equilibrium geometry.

PMID- 12010066
TI  - Thermal dissociation of protein-oligosaccharide complexes in the gas phase:
      mapping the intrinsic intermolecular interactions.
AB  - Blackbody infrared radiative dissociation (BIRD) and functional group replacement
      are used to map the location and strength of hydrogen bonds between an antibody
      single chain fragment (scFv) and its natural trisaccharide receptor, alpha-D-Galp
      (1-->2)[alpha-D-Abep (1-->3)]alpha-D-Manp1-->OMe (1), in the gaseous, multiply
      protonated complex. Arrhenius activation parameters (E(a) and A) are reported for
      the loss of 1 and a series of monodeoxy trisaccharide congeners (5-8 identical
      with tri) from the (scFv + tri + 10H)(+10) complex. The energetic contribution of
      the specific oligosaccharide OH groups to the stability of the (scFv + 1 +
      10H)(+10) complex is determined from the differences in E(a) measured for the
      trisaccharide analogues and 1 (55.2 kcal/mol). A decrease of 6 to 11 kcal/mol in
      E(a), measured for the monodeoxy trisaccharides, indicates that the deleted OH
      groups interact strongly with the scFv and that they account for a majority of
      the stabilizing intermolecular interactions. A partial map of the hydrogen bond
      donor/acceptor groups of 1 and the strength of the interactions is presented for
      the protonated +10 complex. A comparison of the gas-phase map with the crystal
      structure indicates that significant structural differences exist. The hydroxyl
      groups located outside of the binding pocket, and exposed to solvent in solution,
      participate in new protein-oligosaccharide hydrogen bonds in the gas phase. The
      decrease in kinetic and energetic stability of the (scFv + 2 + nH)(n)()(+)
      complex with increasing charge-state is attributed to conformational differences
      in the binding region induced by electrostatic repulsion. The similarity in the
      Arrhenius parameters for the +9 and +10 charge states suggests that repulsion
      effects on the structure of the binding region are negligible below +11.

PMID- 12010067
TI  - Measurements of the photodissociation quantum yields of MbNO and MbO(2) and the
      vibrational relaxation of the six-coordinate heme species.
AB  - The (t approximately 0) photodissociation quantum yields (Y(0)) of MbNO and
      MbO(2) are measured to be 50 +/- 5 and 28 +/- 6%, respectively, using MbCO (Y(0)
      = 100%) as a reference. When photolysis does not take place, we find that a
      significant portion of the photon energy contributes to heating of the residual
      six-coordinate heme (MbNO and MbO(2)). The time constant for vibrational
      relaxation of the six-coordinate ligand-bound heme is found to be close to 1 ps
      for both samples. The MbO(2) sample also shows a approximately 4-ps optical
      response that is assigned to a rapid phase (25-30% amplitude) of O(2) geminate
      rebinding. We observe no additional geminate recombination in the MbO(2) sample
      out to 120 ps. In contrast, the MbNO sample displays significant geminate
      recombination over the first 120 ps, which can be adequately fit with two
      exponentials whose amplitudes and time constants appear to depend weakly on the
      pump wavelength. This more complex kinetic behavior conceivably arises due to
      heating of the photodissociated heme and its effect on the geminate recombination
      as the system cools. Overall, the data are consistent with a hypothesis that
      distortions along the iron-ligand bending coordinate play a key role in the
      photodissociation process. The transient formation of an unphotolyzable FeO(2)
      side-on binding geometry is suggested to be responsible for the lowered quantum
      yield of MbO(2) relative to MbNO.

PMID- 12010068
TI  - Cellular and molecular pathophysiology of cutaneous drug reactions.
AB  - Hypersensitivity reactions to drugs can cause a variety of skin diseases like
      maculopapular, bullous and pustular eruptions. In recent years increasing
      evidence indicates the important role of T cells in these drug-induced skin
      diseases. Analysis of such drug-specific T cell clones has revealed that drugs
      can be recognized by alpha beta-T cell receptors, not only if bound covalently to
      peptides, but also if the drug binds in a rather labile way to the presenting
      major histocompatibility complex (MHC)-peptide. This presentation is sufficient
      to stimulate T cells. In maculopapular exanthema (MPE), histopathological
      analysis typically shows a dominant T cell infiltration together with a vacuolar
      interface dermatitis. Immunohistochemical studies demonstrate the presence of
      cytotoxic CD4+ and to a lesser degree of CD8+ T cells, which contain perforin and
      granzyme B. They are close to keratinocytes that show signs of cell destruction.
      Expression of Fas ligand is barely detectable, suggesting that cytotoxic granule
      exocytosis may be the dominant pathway leading to keratinocyte cell damage. While
      in MPE, the killing of cells seems to be predominantly mediated by CD4+ T cells,
      patients with bullous skin disease show a strong CD8+ T cell migration to the
      epidermis. This is probably due to a preferential presentation of the drug by MHC
      class I molecules, and a more extensive killing of cells that present drugs on
      MHC class I molecules. This might lead to bullous skin diseases. In addition to
      the presence of cytotoxic T cells, drug-specific T cells also orchestrate the
      inflammatory skin reaction through the release and induction of various cytokines
      [i.e. interleukin (IL)-5, IL-6, tumor necrosis factor-alpha and interferon-gamma]
      and chemokines (RANTES, eotaxin or IL-8). The increased expression of these
      mediators seems to contribute to the generation of tissue and blood eosinophilia,
      a hallmark of many drug-induced allergic reactions. However, in acute generalized
      exanthematous pustulosis (a peculiar form of drug allergy), neutrophils represent
      the predominant cell type within pustules, probably due to their recruitment by
      IL-8 secreting drug specific T cells and keratinocytes.

PMID- 12010069
TI  - Photosensitivity disorders: cause, effect and management.
AB  - Abnormal photosensitivity syndromes form a significant and common group of skin
      diseases. They include primary (idiopathic) photodermatoses such as polymorphic
      light eruption (PLE), chronic actinic dermatitis (CAD), actinic prurigo, hydroa
      vacciniforme and solar urticaria, in addition to drug- and chemical-induced
      photosensitivity and photo-exacerbated dermatoses. They can be extremely
      disabling and difficult to diagnose. PLE, characterized by a recurrent pruritic
      papulo-vesicular eruption of affected skin within hours of sun exposure, is best
      managed by restriction of ultraviolet radiation (UVR) exposure and the use of
      high sun protection factor (SPF) sunscreens. If these measures are insufficient,
      prophylactic phototherapy with PUVA, broadband UVB or narrowband UVB (TL-01) for
      several weeks during spring may be necessary. CAD manifests as a dermatitis of
      chronically sun-exposed skin. Again, UVR exposure needs to be restricted;
      cyclosporine, azathioprine or PUVA may also be necessary. Actinic prurigo is
      characterized by the presence of excoriated papules and nodules on the face and
      limbs, most prominent and numerous distally. Actinic prurigo is managed again by
      restriction of UVR and the use of high SPF sunscreens; PUVA or broadband UVB
      therapy, or low doses of thalidomide may be necessary. Hydroa vacciniforme causes
      crops of discrete erythematous macules, 2 to 3mm in size, that evolve into
      blisters within a couple of days of sun exposure. Treatment for this rare disease
      is difficult; absorbent sunscreens and restricted UVR exposure may help. Solar
      urticaria is characterized by acute erythema and urticarial wealing after
      exposure to UVR. Treatment options for solar urticaria include non-sedating
      antihistamines such as fexofenadine and cetirizine; other options include
      absorbent sunscreens, restriction of UVR at the relevant wavelength, maintenance
      of a non-responsive state with natural or artificial light exposure and
      plasmapheresis. Industrial, cosmetic and therapeutic agents can induce exogenous
      drug- or chemical-induced photosensitivity. The clinical pattern is highly
      varied, depending on the agent; treatment is based on removal of the
      photosensitizer along with restriction of UVR exposure. Predominantly non
      photosensitive dermatoses may also be exacerbated or precipitated by UVR;
      exposure to UVR should be reduced and sunscreens should be advocated, along with
      appropriate treatment of the underlying disease.

PMID- 12010070
TI  - Basal cell carcinoma: treatment options and prognosis, a scientific approach to a
      common malignancy.
AB  - The incidence of basal cell carcinoma is rapidly increasing and a number of
      treatment modalities are available. Treatment of basal cell carcinoma includes
      both surgical and nonsurgical approaches, some of which are traditional, and
      others experimental. The treatment modality utilized is dependent on both the
      tumor type and the patient. In order to choose between therapies, evidence-based
      research is necessary. In an extensive review of the literature concerning
      treatment options for patients with basal cell carcinoma, we found that there are
      a limited number of comparative, prospective, randomized, long-term follow-up
      studies. Based on the results of the available studies, surgical excision, Mohs
      surgery and cryosurgery are the three standard therapies of choice. Other
      treatment modalities should be considered secondary choices. There are also
      promising new treatment options, such as photodynamic therapy, which need further
      investigation. Special attention is needed when treating the more aggressive
      subtypes of the disease, such as the micronodular, infiltrative, adenoid and
      morpheic forms of basal cell carcinoma, as well as bigger basal cell carcinomas
      and basal cell carcinoma recurrences.

PMID- 12010071
TI  - The acidic milieu of the horny layer: new findings on the physiology and
      pathophysiology of skin pH.
AB  - The acidic pH of the horny layer, measurable on the skin surface, has long been
      regarded as a result of exocrine secretion of the skin glands. The 'acid mantle'
      was thought to regulate the bacterial skin flora and to be sensitive primarily to
      skin cleansing procedures. In recent years, an increasing number of
      investigations have been published on the changes in, and constituents and
      functions of, the pH of the deeper layers of the stratum corneum, as well as on
      the influence of physiological and pathological factors. A central role for the
      acidic milieu as a regulating factor in stratum corneum homeostasis is now
      emerging. This has relevance to the integrity of the barrier function, from
      normal maturation of the stratum corneum lipids through to desquamation. Changes
      in the pH and the organic factors influencing it appear to play a role, not only
      in the pathogenesis, prevention and treatment of irritant contact dermatitis, but
      also of atopic dermatitis and ichthyosis and in wound healing. On the basis of
      these findings, a broader concept, exceeding the superficial 'acid mantle'
      theory, has been formulated.

PMID- 12010072
TI  - Helicobacter pylori infection in skin diseases: a critical appraisal.
AB  - More than 50% of the human population have long-term Helicobacter pylori
      infection, causing, in some cases, severe diseases such as peptic ulcers and
      stomach cancer. In the last few years several extra-gastrointestinal disorders
      have been associated with H. pylori infection. This review summarized the current
      medical literature, identified through hand searching and MEDLINE research,
      including our own studies, with regard to H. pylori and skin diseases. From the
      literature it can be seen that the role of H. pylori in skin diseases is still a
      controversial subject. Randomized controlled trials with adequate masking and
      sample sizes are still lacking. The best evidence comes from studies
      investigating chronic urticaria in which chronic urticaria disappeared in many
      patients with H. pylori infection after careful eradication of the H. pylori.
      Moreover, there are promising recent reports of beneficial H. pylori eradication
      in Behcet's disease, pruritus cutaneus, prurigo chronica, prurigo nodularis and
      in some patients with lichen planus, but not in rosacea or psoriasis. Before any
      conclusions with respect to other skin diseases such as atopic dermatitis,
      Schoenlein-Henoch Purpura, Sweet's syndrome, Sjogren syndrome or systemic
      sclerosis may be drawn, additional randomized, double-blinded and placebo
      controlled studies including adequate diagnostic schedules, sufficient
      eradication treatment protocols, confirmation of eradication and adequate control
      groups are needed. The cutaneous pathology of H. pylori is far from being clear,
      but it is speculated that the systemic effects may involve increased mucosal
      permeability to alimentary antigens, immunomodulation, an autoimmune mechanism or
      the impairment of vascular integrity.

PMID- 12010073
TI  - Importance of irritant contact dermatitis in occupational skin disease.
AB  - BACKGROUND: Irritant contact dermatitis (ICD), provoked by work materials or
      workflows, is believed to be a frequent cause of occupational skin disease (OSD).
      Data of incidence rates of ICD within different occupations are inadequate.
      OBJECTIVE: We conducted a population-based study to identify occupational groups
      at risk for irritant and allergic contact dermatitis (ACD). METHODS: The data are
      based on all workers' compensation claims reported to our register of OSDs in
      Northern Bavaria [Berufskrankheitenregister Haut-Nordbayern (BKH-N)], Germany.
      RESULTS: From 1990 to 1999, 5285 patients had their cases completely assessed and
      recorded by government-employed physicians. We calculated the incidence rates of
      ICD and ACD in various occupations, divided into 24 occupational groups, in co
      operation with the German State Institute of Labor and Occupation; there were a
      known total number of employees in each of the occupations. In these groups 3097
      (59%) patients with OSD were observed, with an overall annual incidence rate of
      4.5 patients per 10,000 workers for ICD, compared with 4.1 patients per 10,000
      workers for ACD. The highest ICD annual incidence rates were found in
      hairdressers (46.9 per 10,000 workers per year), bakers (23.5 per 10,000 workers
      per year), and pastry cooks (16.9 per 10,000 workers per year); at the same time
      ICD was the main diagnosis of OSD in pastry cooks (76%), cooks (69%), food
      processing industry workers and butchers (63%), mechanics (60%), and locksmiths
      and automobile mechanics (59%). The results of a questionnaire showed frequent
      skin contact with detergents (52%), disinfectants (24%), and acidic and alkaline
      chemicals (24%) in the workplace. CONCLUSION: Based on the incidence data of the
      BKH-N, this study identified occupational groups with a high risk of ICD.
      Different frequencies of ICD and ACD within a single group are demonstrated. The
      frequent usage of detergents is being addressed because of the introduction of
      German legislation of recent date (the Approved Code of Practice 531 on 'wet
      work').

PMID- 12010075
TI  - Vaccines against genital herpes: progress and limitations.
AB  - Herpes simplex viruses (HSV) cause lifelong persistent infections with numerous
      disease manifestations. Genital herpes infections are widespread in populations
      throughout the world and a vaccine to protect against or subdue established
      genital herpes infections has been under development for decades. Vaccine
      mediated protection against persistent viral infections can be extremely
      difficult to achieve. The more rapidly a virus reaches its target tissue for
      persistence, the more vigorously a vaccine-induced immune response must defend
      the vaccinated individual. After exposure to HSV through sexual contact, only a
      few days are required for the virus to establish latent infection of its host.
      Despite numerous improvements, traditional vaccine approaches of whole virus or
      protein subunits have met with only marginal success. The many disappointments
      have heightened interest in determining correlates of immune protection, studies
      pursued both in animal models and in humans. They have also led to reassessment
      of the goals of vaccination. Necessity has sparked several creative new vaccine
      approaches involving nucleic acid or live attenuated viruses and vectors. With
      improved concepts of protective immune responses has come fervent discussion of
      the means to stimulate and maintain cell-mediated immunity. The result of this
      work is likely to be a more thorough understanding of antiviral immunity in the
      genital mucosa and the nervous system, and of HSV pathogenesis and immune evasion
      strategies, as additional strides are taken toward the goal of a successful
      vaccine with which to confront HSV.

PMID- 12010076
TI  - Management of cutaneous erythrasma.
AB  - Corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of
      erythrasma and is the most common cause of interdigital foot infections. It is
      found mostly in occluded intertriginous areas such as the axillae, inframammary
      areas, interspaces of the toes, intergluteal and crural folds, and is more common
      in individuals with diabetes mellitus than other clinical patients. This organism
      can be isolated from a cutaneous site along with a concurrent dermatophyte or
      Candida albicans infection. The differential diagnosis of erythrasma includes
      psoriasis, dermatophytosis, candidiasis and intertrigo, and methods for
      differentiating include Wood's light examination and bacterial and mycological
      cultures. Erythromycin 250mg four times daily for 14 days is the treatment of
      choice and other antibacterials include tetracycline and chloramphenicol;
      however, the use of chloramphenicol is limited by bone marrow suppression
      potentially leading to neutropenia, agranulocytosis and aplastic anaemia. Further
      studies are needed but clarithromycin may be an additional drug for use in the
      future. Where there is therapeutic failure or intertriginous involvement, topical
      solutions such as clindamycin, Whitfield's ointment, sodium fusidate ointment and
      antibacterial soaps may be required for both treatment and prophylaxis. Limited
      studies on the efficacy of these medications exist, however, systemic
      erythromycin demonstrates cure rates as high as 100%. Compared with
      tetracyclines, systemic erythromycin has greater efficacy in patients with
      involvement of the axillae and groin, and similar efficacy for interdigital
      infections. Whitfield's ointment has equal efficacy to systemic erythromycin in
      the axillae and groin, but shows greater efficacy in the interdigital areas and
      is comparable with 2% sodium fusidate ointment for treatment of all areas.
      Adverse drug effects and potential drug interactions need to be considered. No
      cost-effectiveness data are available but there are limited data on cost-related
      treatment issues. A guideline is proposed for the detection, evaluation,
      treatment and prophylaxis of this cutaneous eruption.

PMID- 12010078
TI  - Lansoprazole for maintenance of remission of erosive oesophagitis.
AB  - Gastro-oesophageal reflux disease, which is experienced daily by a significant
      proportion of individuals, may result in serious sequelae such as erosive
      oesophagitis. Short-term treatment with acid antisecretory therapy (a proton pump
      inhibitor or a histamine H(2) receptor antagonist) is highly effective in healing
      the erosive oesophagitis lesion. However, numerous studies confirm that unless
      maintenance therapy is initiated virtually all patients will experience
      oesophagitis relapse within 1 year, as well as an increasing severity of
      oesophagitis and risk for complications such as Barrett's oesophagus and
      adenocarcinoma. Studies evaluating the efficacy of proton pump inhibitor and H(2)
      antagonist maintenance therapy have found that only the proton pump inhibitors
      significantly reduce the incidence of oesophagitis relapse. Pharmacoeconomic
      studies have also confirmed that proton pump inhibitor maintenance therapy is
      cost effective, by virtue of the ability of these agents to reduce the incidence
      of relapse as well as prolong the time to relapse and increase the number of
      weeks per year that patients are without symptoms. Lansoprazole, a member of the
      proton pump inhibitor class of agents, has been extensively studied in the
      treatment of patients with a variety of acid-related disorders. Among those with
      erosive oesophagitis, maintenance therapy with lansoprazole 15 or 30mg once daily
      is highly effective in preventing relapse. Studies have documented that
      lansoprazole 15 and 30mg once daily for six months prevents oesophagitis relapse
      in up to 81 and 93% of patients, respectively, with comparable percentages of
      patients remaining in remission after 1 year of treatment. These high rates of
      remission have also been observed in studies of patients with lesions that were
      difficult to heal at baseline (resistant to healing with at least 3 months of
      H(2) antagonist therapy). Moreover, lansoprazole produces high remission rates
      regardless of the grade of erosive oesophagitis before acute healing. Among
      symptomatic patients with heartburn, lansoprazole provides rapid and effective
      relief of daytime and night-time heartburn and prevents relapse of symptoms.
      Lansoprazole has a wide margin of safety and is well tolerated when administered
      as monotherapy in short- and long-term clinical trials. Taken together these data
      suggest that proton pump inhibitor therapy represents the preferred and ideal
      long-term management strategy for the patient with erosive oesophagitis.
      Lansoprazole is a well-established member of this class of agents and, as such,
      has an extensive body of literature that supports its safety, tolerability and
      clinical efficacy in preventing relapse in these patients.

PMID- 12010077
TI  - Sickle cell anaemia: progress in pathogenesis and treatment.
AB  - The phenotypic expression of sickle cell anaemia varies greatly among patients
      and longitudinally in the same patient. It influences all aspects of the life of
      affected individuals including social interactions, intimate relationships,
      family relations, peer interactions, education, employment, spirituality and
      religiosity. The clinical manifestations of sickle cell anaemia are protean and
      fall into three major categories: anaemia and its sequelae;pain and related
      issues; andorgan failure including infection. Recent studies on the pathogenesis
      of sickle cell anaemia have centred on the sequence of events that occur between
      polymerisation of deoxy haemoglobin (Hb) S and vaso-occlusion. Cellular
      dehydration, inflammatory response and reperfusion injury seem to be important
      pathophysiological mechanisms. Management of sickle cell anaemia continues to be
      primarily palliative in nature, including supportive, symptomatic and
      preventative approaches to therapy. Empowerment and education are the major
      aspects of supportive care. Symptomatic management includes pain management,
      blood transfusion and treatment of organ failure. Pain managment should follow
      certain priniciples that include assessment, individualisation of therapy and
      proper utilisation of opioid and nonopioid analgesics in order to acheive
      adequate pain relief. Blood selected for transfusion should be leuko-reduced and
      phenotypically matched for the C, E and Kell antigens. Exchange transfusion is
      indicated in patients who are transfused chronically in order to prevent or delay
      the onset of iron-overload. Acute chest syndrome is the most common form of organ
      failure and its management should be agressive, including adequate ventilation,
      multiple antibacterials and simple or exchange blood transfusion depending on its
      severity. Preventitive therapy includes prophylactic penicillin in infants and
      children, blood transfusion (preferably exchange transfusion) in patients with
      stroke, and hydroxyurea in patients with frequent acute painful episodes. Bone
      marrow and cord blood transplantation have been successful modalities of curative
      therapy in selected children with sickle cell anaemia. Newer approaches to
      preventative therapy include cellular rehydration with agents that inhibit the
      Gardos channel or the KCl co-transport channel. Curative gene therapy continues
      to be investigational at the level of the test tube and transgenic mouse models.

PMID- 12010079
TI  - ET-743.
AB  - ET-743 is a novel antineoplastic DNA-binding agent derived from the marine
      tunicate Ecteinascidia turbinata. It has significant cytotoxic activity against
      soft tissue sarcomas (STS). It also has in vitro activity against melanoma,
      breast, ovarian, colon, renal, non-small cell lung and prostate carcinomas. The
      drug has unique mechanism of action which includes in vitro inhibition of
      transcription-dependent nucleotide excision repair pathways and inhibition of
      cell cycle progression leading to p53-independent apoptosis. It also selectively
      inhibits transcriptional activation of multidrug-resistance (MDR1) gene in human
      sarcoma cells in vivo. The efficacy of ET-743 has been investigated in patients
      with advanced STS in three multicentre phase II clinical trials. Patients
      receiving ET-743 as second- or third-line treatment had partial tumour response
      rates of 6 to 8%. Patients receiving ET-743 as first-line chemotherapy had a
      partial response rate of 18%. Forty-two to 50% of all patients in these trials
      achieved stable disease. All responses were durable up to 14 months. A pooled
      analysis of the three multicentre phase II trials showed the following: median
      overall survival time of 10.2 months, 1-year survival rate of 40% and 6-month
      progression-free rate of 27.2%. ET-743 is generally well tolerated. The most
      common adverse events in clinical trials were non-cumulative haematological and
      hepatic toxicities. Transient and reversible elevation of hepatic transaminases,
      nausea, vomiting and asthenia were common but seldom severe and never treatment
      limiting. Mucositis, alopecia and cardiac or neurotoxicities were not observed.

PMID- 12010082
TI  - Tiotropium bromide.
AB  - Tiotropium bromide is an anticholinergic bronchodilator that antagonises
      muscarinic M(1), M(2) and M(3) receptors. It dissociates more slowly from M(1)
      receptors and, importantly, from M(3) receptors (which are located in bronchial
      smooth muscle) than from M(2) receptors and subsequently has a long duration of
      action permitting once-daily administration. In patients with chronic obstructive
      pulmonary disease (COPD), tiotropium 18microg once daily significantly improved
      lung function compared with placebo and ipratropium 40microg four times daily in
      1-year trials or salmeterol 50microg twice daily in a 6-month study. The
      incidence of COPD exacerbations decreased and use of rescue medication was lower
      with tiotropium compared with placebo or ipratropium. There was no evidence of
      tachyphylaxis during 1-year treatment with tiotropium. Compared with placebo,
      salmeterol and ipratropium, tiotropium produced significant improvements in
      patients' perception of dyspnoea and health-related quality of life. Tiotropium
      is generally well tolerated; dry mouth is the most common drug-related adverse
      event, occurring in about 10 to 16% of patients in clinical trials.

PMID- 12010086
TI  - Pegfilgrastim.
AB  - Pegfilgrastim is a covalent conjugant of filgrastim (a recombinant human
      granulocyte colony-stimulating factor) and monomethoxypolyethylene glycol. It is
      administered as a single dose per myelosuppressive chemotherapy cycle to decrease
      the incidence of infection, as manifest by febrile neutropenia, in patients with
      nonmyeloid cancer. Pegfilgrastim increases the terminal elimination half-life and
      decreases the apparent serum clearance of the drug in patients with nonmyeloid
      cancer. Serum concentrations of pegfilgrastim remain elevated during neutropenia
      but decline when the neutrophil count increases. In phase III trials in patients
      with breast cancer and in a phase II trial in patients with non-Hodgkin's
      lymphoma or Hodgkin's disease, the mean duration of grade 4 neutropenia and the
      time to absolute neutrophil recovery during cycle 1 of chemotherapy was similar
      in recipients of single-dose pegfilgrastim or daily filgrastim. In the larger of
      two phase III trials in patients with breast cancer, the incidence of febrile
      neutropenia over four cycles of chemotherapy was significantly lower in
      recipients of single-dose pegfilgrastim than that in recipients of daily
      injections of filgrastim. Moreover, the mean duration of grade 4 neutropenia in
      cycles 2 to 4 of chemotherapy was significantly lower in recipients of
      pegfilgrastim than that in recipients of daily filgrastim. In comparative trials,
      there were no differences in the incidence and severity of adverse events,
      including skeletal pain, between single-dose pegfilgrastim and daily filgrastim
      in patients with nonmyeloid cancer receiving myelosuppressive chemotherapy.

PMID- 12010089
TI  - Ziprasidone: a review of its use in schizophrenia and schizoaffective disorder.
AB  - Ziprasidone is a novel antipsychotic agent with a pharmacological profile
      distinct from that of other currently available novel or classical
      antipsychotics. In preclinical studies, ziprasidone was predicted to have
      efficacy against positive, negative and affective symptoms of schizophrenia with
      a favourable tolerability profile, including a low propensity to induce
      extrapyramidal adverse effects. The drug has been administered orally to >300
      patients with an acute exacerbation of schizophrenia or schizoaffective disorder
      in published 4- to 6-week randomised, double-blind trials. When given twice
      daily, at dosages of between 80 and 160 mg/day, ziprasidone produced
      significantly greater improvements in overall symptomatology than placebo. In the
      largest study, ziprasidone 80 or 160 mg/day was also significantly more effective
      than placebo in reducing negative symptoms and, at 160 mg/day, was significantly
      more effective than placebo in improving depressive symptoms in patients with
      associated clinically significant depression. Data from a 4-week trial indicate
      that ziprasidone 160 mg/day has similar efficacy to haloperidol 15 mg/day.
      Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to
      prevention of impending relapse and improvement of negative symptoms in 294
      stable patients with chronic schizophrenia who were treated for up to 1 year. In
      addition, significantly more ziprasidone than haloperidol recipients achieved a
      negative symptom response in a 28-week study involving 301 stable patients with
      chronic or subchronic schizophrenia. In general, oral ziprasidone is well
      tolerated with an overall incidence of adverse events similar to placebo.
      Importantly, the drug has a low propensity to induce extrapyramidal effects and a
      negligible effect on bodyweight. Ziprasidone is associated with slight
      prolongation of the QTc interval; the clinical significance of this is not yet
      clear. The drug does not appear to be associated with sustained elevation of
      plasma prolactin concentrations. Preliminary data indicate that long-term oral
      ziprasidone treatment is well tolerated. Ziprasidone is the only novel
      antipsychotic currently available in a rapid-acting intramuscular formulation.
      Short-term treatment with intramuscular ziprasidone was effective and well
      tolerated in patients with acute agitation associated with psychosis. In
      addition, intramuscular ziprasidone reduced agitation scores by a significantly
      greater extent than haloperidol in a study involving patients with acute
      agitation associated with psychosis. CONCLUSIONS: Ziprasidone is a promising new
      antipsychotic that has shown significant efficacy in the oral treatment of
      patients with schizophrenia or schizoaffective disorder. The drug is well
      tolerated with a low propensity to induce extrapyramidal effects and a negligible
      effect on bodyweight. In addition, intramuscular ziprasidone shows efficacy and
      good tolerability in the treatment of acute agitation associated with psychotic
      disorders.

PMID- 12010091
TI  - Outcome of conservative versus interventional treatment of subclavian artery
      stenosis.
AB  - PURPOSE: To compare the outcome of conservative treatment versus percutaneous
      transluminal angioplasty (PTA) of subclavian artery stenosis in terms of long
      term hemodynamic and symptomatic outcome in a retrospective, nonrandomized study.
      METHODS: Within a 14-year period, 295 consecutive inpatients were treated for
      subclavian artery stenosis. Excluding 21 (7%) surgical cases, the remaining 274
      patients were treated either conservatively (n = 165) or with PTA (n = 109).
      Medical history, physical findings, and sonographic and angiographic data were
      recorded from the medical records of the 223 (81%) patients who were followed
      until the year 2000; 166 patients were then reinvestigated with oscillography,
      Doppler measurements, and duplex sonography. Outcomes of conservative versus
      interventional therapy were analyzed based on the intention to treat principle.
      RESULTS: After a median 42-month follow-up (interquartile range 18-85), patients
      treated with PTA had a 60% risk reduction for hemodynamic subclavian stenosis
      compared to conservative treatment (adjusted hazard ratio 0.4, 95% confidence
      interval 0.2-0.6, p<0.0001). However, the risk of having a symptomatic stenosis
      at the time of follow-up did not differ between the treatment groups (p=0.3).
      CONCLUSIONS: Endovascular revascularization improves the long-term hemodynamic
      outcome in patients with subclavian stenosis, but many conservatively treated
      patients become asymptomatic during follow-up. Interventional treatment may be
      considered primarily for patients with severe symptoms of vertebrobasilar
      insufficiency, critical ischemia, or peripheral emboli.

PMID- 12010090
TI  - Candesartan cilexetil: an update of its use in essential hypertension.
AB  - Candesartan cilexetil is converted to the angiotensin II receptor antagonist
      candesartan during absorption from the gastrointestinal tract. The selective and
      competitive binding of candesartan to the angiotensin II type 1 (AT(1)) receptor
      prevents binding of angiotensin II, a key mediator in the renin-angiotensin
      system. Significant reductions in systolic BP and diastolic BP are achieved with
      a once-daily dosage of candesartan cilexetil 2 to 32 mg/day in patients with mild
      to moderate hypertension. In randomised studies, candesartan cilexetil 8 to 16
      mg/day was at least as effective as therapeutic dosages of losartan or other
      angiotensin II receptor antagonists. At a dosage of up to 32 mg/day candesartan
      cilexetil demonstrated greater antihypertensive efficacy than losartan 50 or 100
      mg/day. In comparative trials, candesartan cilexetil demonstrated similar or
      greater antihypertensive efficacy compared with enalapril or hydrochlorothiazide
      and equivalent efficacy compared with amlodipine. The efficacy of candesartan
      cilexetil is not affected by age, and the drug provided significant BP reductions
      in Black patients and in those with severe hypertension. Long-term clinical
      studies to assess the effects of treatment with candesartan cilexetil on
      cardiovascular morbidity and mortality are ongoing. Regression of left
      ventricular hypertrophy has been seen with candesartan cilexetil treatment in
      patients with hypertension. Furthermore, the drug has favourable effects on renal
      function in patients with hypertension with or without coexisting diabetes
      mellitus. Renal vascular resistance and albumin excretion were reduced following
      treatment with candesartan cilexetil. Glucose homeostasis and lipid metabolism
      were not affected by treatment in patients with type 2 diabetes mellitus.
      Candesartan cilexetil is well tolerated and is not associated with cough, a
      common adverse effect of angiotensin converting enzyme inhibitor treatment. A
      pooled analysis of clinical trials found that the tolerability profile of
      candesartan cilexetil is not significantly different from that of placebo.
      Adverse events are not dose-related and are generally of mild to moderate
      severity. CONCLUSIONS: Candesartan cilexetil is an effective antihypertensive
      agent with a tolerability profile similar to that of placebo. Comparative data
      indicate that candesartan cilexetil has antihypertensive efficacy equivalent to
      that of other major classes of antihypertensive agents and has a long duration of
      action. Therefore, candesartan cilexetil is a useful therapeutic option in the
      management of patients with hypertension.

PMID- 12010092
TI  - Use of the Parodi anti-embolism system in carotid stenting: Italian trial
      results.
AB  - PURPOSE: To investigate the safety and efficacy of the Parodi anti-embolism
      system (PAES) in establishing flow reversal in the internal carotid artery (ICA)
      as a means of protecting against embolic phenomena during carotid stenting.
      METHODS: Seven centers participated in a nonrandomized, prospective trial of
      carotid angioplasty and stenting under PAES protection in 30 patients (22 men;
      mean age 72 years, range 49-88) with 15 symptomatic (>70%) and 15 asymptomatic
      (>80%) stenotic ICAs. Safety was defined as achieving sufficient brain
      oxygenation during flow reversal as determined by level of awareness and motor
      control. The presence of new or enhanced neurological deficits and death were
      endpoints. Performance was based on angiographic evidence of successful
      retrograde flow. RESULTS: The PAES was positioned in all 30 patients, but
      technical error and access-related difficulties prevented establishment of
      reversed flow in 2. Among the 28 (93%) patients treated under PAES protection, 1
      patient developed aphasia after flow reversal, necessitating balloon deflation
      between subsequent stages of the procedure. Three other adverse events included 1
      case of bradycardia and 2 cases of hypotension, with dysarthria and facial
      paresis in one and temporary loss of consciousness in the other. All events
      resolved with appropriate therapy, and there was no change from baseline in the
      neurological status or brain scans at 24 hours. There were no strokes or
      neurological deficits at 30 days. CONCLUSIONS: The PAES appears to be a safe and
      effective means of providing protection from embolic complications during carotid
      stenting.

PMID- 12010093
TI  - Efficacy of a nitinol filter device in the prevention of embolic events during
      carotid interventions.
AB  - PURPOSE: To evaluate the feasibility, safety, and efficacy of the TRAP Vascular
      Filtration System (VFS) during carotid interventions as a deterrent to embolic
      complications. METHODS: Thirty-one consecutive patients (18 men; mean age 72 +/-
      8 years) gave informed consent to undergo elective percutaneous angioplasty and
      stenting of the extracranial carotid artery protected by the TRAP VFS, a nitinol
      basket filter system. RESULTS: The TRAP VFS was delivered and retrieved safely in
      all patients; procedural success for carotid stenting was 100%. In 3 (9.7%)
      cases, the filters were positioned after lesion predilation. Nearly half (13,
      41.9%) of the retrieved filters contained visible plaque debris that histology
      identified as cholesterol crystals, fibrin material, atheromatous plaque, and
      macrophage foam cells. There were no symptomatic major or minor neurological
      complications encountered in this cohort during hospitalization. CONCLUSIONS: Our
      data indicate that percutaneous dilation and stenting of the carotid artery
      protected by TRAP VFS appears to be feasible, safe, and effective in preventing
      cerebral embolization.

PMID- 12010094
TI  - Partially clipped intracranial aneurysm obliterated with combined stent and coil
      implantation.
AB  - PURPOSE: To report a case of endovascular stent placement to assist stable coil
      deployment in a symptomatic, wide-necked, partially clipped aneurysm. CASE
      REPORT: A 48-year-old woman presented for endovascular treatment of a symptomatic
      posterior communicating artery aneurysm remnant that was surgically clipped 10
      years ago. A 3.5-mm x 12-mm balloon-expandable stent was placed across the
      aneurysm orifice followed by complete obliteration of the remnant with coils
      implanted through the stent mesh. Digital subtraction angiography documented
      continued patency of the arterial lumen and complete obliteration of the aneurysm
      at 11 months. CONCLUSIONS: Partial aneurysm clipping may assist or complicate
      secondary interventional procedures and interfere with correct visualization of
      the neck. Stent placement obviates the need for the balloon-assist method of coil
      embolization for wide-necked aneurysm remnants, acting as a mechanical barrier to
      hold the coils in a very unfavorable anatomy.

PMID- 12010095
TI  - Simultaneous stent-graft repair of thoracic and infrarenal abdominal aortic
      aneurysms.
AB  - PURPOSE: To describe a technique for concomitant endovascular stent-graft repair
      of thoracic and infrarenal abdominal aortic aneurysms. CASE REPORT: A 68-year-old
      man was found to have concomitant thoracic and abdominal aortic aneurysms. Both
      of the aneurysms were excluded successfully in one procedure using Talent stent
      grafts. The patient tolerated the procedure well and was discharged on
      postoperative day 4. Aside from an infected groin wound, the patient did not have
      any complications. Computed tomographic scans at 6, 12, and 18 months showed
      proper position of both stents without evidence of endoleak. CONCLUSIONS:
      Simultaneous endovascular treatment of thoracic and infrarenal abdominal aortic
      aneurysms may represent a viable alternative for therapy in some patients.

PMID- 12010096
TI  - Detection of endoleak with enhanced ultrasound imaging: comparison with biphasic
      computed tomography.
AB  - PURPOSE: To compare unenhanced and enhanced ultrasound imaging to biphasic
      computed tomography (CT) in the detection of endoleak after endovascular
      abdominal aortic aneurysm (AAA) repair. METHODS: Fifty-three patients (44 men;
      mean age 70 years) were examined during 96 follow-up visits after endovascular
      AAA repair. All patients had color Doppler and power Doppler ultrasound studies
      performed before and after the administration of an ultrasound contrast agent.
      Biphasic (arterial and delayed) CT was performed on the same day, and the
      ultrasound and CT studies were independently scored to record the presence or
      absence of endoleak and the level of confidence in the observation. RESULTS: The
      sensitivity of the ultrasound techniques to detect endoleak improved with the use
      of ultrasound contrast media, ranging from a low of 12% with unenhanced color
      Doppler to 50% with enhanced power Doppler. However, the enhanced power Doppler
      failed to detect 9 type II endoleaks identified by CT (86% negative predictive
      value for endoleak). There were only 2 graft-related endoleaks in the study; one
      was diagnosed from the ultrasound image, but the other had nondiagnostic
      ultrasound scans because of poor views. CONCLUSIONS: Ultrasound scanning with or
      without contrast enhancement was not as reliable as CT in diagnosing type II
      endoleak. CT imaging remains our surveillance modality of choice.

PMID- 12010097
TI  - Thromboembolic complications after endovascular aortic aneurysm repair.
AB  - PURPOSE: To evaluate the frequency and significance of thromboembolic
      complications following endovascular treatment of aortic aneurysms. METHODS: One
      hundred seventy-four patients (153 men; mean 71.4 years, range 26-90) underwent
      endovascular repair of aneurysms of the thoracic (n = 38) or abdominal (n = 136)
      aorta using a variety of endografts. All patients were examined preprocedurally
      using 3-phase helical computed tomography (CT) to determine appropriate endograft
      size. To exclude the occurrence of infarction in parenchymal organs, the first
      postprocedural CT scan was compared with preoperative findings. Newly recognized
      perfusion deficits were taken as evidence of procedure-related infarction.
      RESULTS: Infarctions were detected in 16 (9.2%) patients: 13 in the kidneys, 2 in
      the spleen, with 1 in the mesentery; only the mesenteric infarction was
      clinically symptomatic. Both splenic infarctions were associated with deployment
      of stent-grafts in the thoracic aorta (5.3% of the 38 patients), while the
      mesenteric and 13 renal infarctions were seen in patients with infrarenal
      abdominal aortic aneurysms (0.7% and 9.6%, respectively, of 136 patients). One
      patient experienced complete thromboembolic occlusion of a renal artery, which
      was partially recanalized with intraoperative lysis. CONCLUSIONS: Thromboembolic
      complications of endovascular aortic aneurysm repairs are not uncommon, and
      although usually asymptomatic, these sequelae have the potential to be life
      threatening. Perfusion abnormalities may respond to immediate lytic therapy with
      complete dissolution of the thrombus in certain isolated cases.

PMID- 12010098
TI  - Endovascular AAA repair: classification of aneurysm sac volumetric change using
      spiral computed tomographic angiography.
AB  - PURPOSE: To classify and analyze the volumetric changes seen on spiral computed
      tomographic angiography (CTA) following endovascular abdominal aortic aneurysm
      (AAA) repair. METHODS: Fifty patients (46 men; mean age 71 years, range 51-83)
      with >1 year of imaging follow-up were retrospectively selected. The volume of
      the aneurysm sac was calculated on standard CT workstations to obtain plots of
      volume changes over time. For the purpose of this study, a 10% change in sac
      volume was considered significant. RESULTS: Over a mean 32-month follow-up, 256
      CTA scans were performed; initial mean sac volume was 259 mL and initial mean AAA
      diameter was 6.5 cm. Six distinct patterns of volume change were recognized:
      group Ia (28 patients, 56%): progressive reduction in aneurysm sac volume; group
      Ib (3 patients, 6%): transient initial increase then same as Ia; group II (4
      patients, 8%): no significant change; group IIIa (5 patients, 10%): late increase
      in volume; group IIIb (8 patients, 16%): progressive increase in volume; and
      group IV (2 patients, 4%): late reduction in volume after secondary intervention.
      Group III changes were associated with endoleak types I and III (p<0.0001).
      CONCLUSIONS: This classification system of spiral CTA volumetric changes features
      6 patterns with recognized clinical significance and predictive value for
      endoleaks. Group I is the ideal outcome when the aneurysm sac shrinks and often
      completely disappears, while group III is associated with types I and type III
      endoleak and should prompt further investigation. Long-term volumetric analysis
      of all patients is advised.

PMID- 12010099
TI  - Emergent repair of a ruptured abdominal aortic aneurysm using an AneuRx stent
      graft.
AB  - PURPOSE: To report a case of ruptured abdominal aortic aneurysm (AAA) treated
      with a commercially available endoluminal graft. CASE REPORT: Ruptured AAA was
      diagnosed in a 58-year-old man with lower abdominal pain, hypotension, and
      syncope. A contrast-enhanced computed tomographic (CT) scan confirmed the
      presence of a 7-cm ruptured infrarenal AAA associated with a large
      retroperitoneal hematoma. The aneurysm was successfully excluded with a
      bifurcated AneuRx stent-graft placed through a femoral approach in an emergent
      procedure. The patient was discharged on the third postoperative day. CT scans at
      1 and 10 months demonstrated complete resolution of the retroperitoneal hematoma
      and continued exclusion of the aneurysm. CONCLUSIONS: The AneuRx stent-graft can
      be successfully applied for the treatment of a ruptured AAA in emergency
      situations.

PMID- 12010100
TI  - CT-guided percutaneous embolization of a lumbar artery maintaining a type II
      endoleak.
AB  - PURPOSE: To demonstrate the possibility of percutaneous embolization of a type II
      endoleak guided by computed tomographic (CT) fluoroscopy. CASE REPORT: A type II
      endoleak maintained by a hypertrophic fourth lumbar artery failed to occlude
      spontaneously 7 months after stent-graft deployment for endovascular repair of an
      infrarenal abdominal aortic aneurysm. A percutaneous procedure was performed to
      eliminate the endoleak using needle puncture and embolization under CT
      fluoroscopic guidance. The sagittal diameter of the aneurysm sac, which had
      remained constant after initial endovascular exclusion, shrank from 5.2 to 4.8 cm
      in the 3 months following embolization. CONCLUSIONS: Percutaneous embolization of
      lumbar branches guided by CT fluoroscopy may be an alternative to other therapies
      for type II endoleaks.

PMID- 12010101
TI  - Endograft fabric disintegration simulating a type II endoleak.
AB  - PURPOSE: To report a case of endograft disintegration misinterpreted as a type II
      endoleak. CASE REPORT: An 86-year-old man underwent successful Vanguard stent
      graft implantation for a 49-mm abdominal aortic aneurysm. At 1 month, a distal
      type I endoleak was repaired, but another endoleak thought to arise from the
      lumbar or inferior mesenteric arteries remained. Multiple interventions to
      embolize the feeding arteries were unsuccessful, and the endoleak persisted. At 1
      year, the leak was still present, and the aneurysm had increased to 69 mm. After
      failing to demonstrate the source of the leak radiographically, surgery was
      performed. At operation, the endoleak was traced to small holes in the graft
      fabric. The endograft was removed without difficulty, and the flow was re
      established with an aortobi-iliac woven graft. CONCLUSIONS: Chronically implanted
      stent-grafts can show signs of failure that are confusing or misleading. Correct
      diagnosis of endoleaks may be difficult, but every effort must be made to
      identify their source. It is vital that no enlarging aneurysm be left untreated.

PMID- 12010102
TI  - Emergency endograft placement for recurrent aortocaval fistula after conventional
      AAA repair.
AB  - PURPOSE: To report a novel case in which a stent-graft was used to emergently
      treat an aortocaval fistula that recurred after conventional abdominal aortic
      aneurysm (AAA) repair. CASE REPORT: A 67-year-old man was treated urgently for
      ruptured AAA with surgical placement of a 16-mm Dacron interposition graft.
      During the procedure, an aortocaval fistula was repaired primarily. The patient
      was discharged in satisfactory condition but returned 20 days later with dyspnea,
      bilateral perimalleolar edema, and a bruit in the mesogastric region. The high
      flow fistula was again present just above the aortic bifurcation at the distal
      anastomosis of the existing graft. The patient's condition deteriorated rapidly,
      so a bifurcated Vanguard stent-graft was deployed in an emergency procedure.
      Subsequent imaging confirmed satisfactory closure of the fistula. The patient was
      discharged 8 days after endograft placement, and he continues to be without signs
      of fistula recurrence at 2 years. CONCLUSIONS: Endograft treatment of vascular
      lesions in the acute setting is becoming more common as our experience with the
      devices grows. Endovascular repair of primary aortocaval fistulas appears to be
      an efficacious and minimally invasive means of dealing with these lesions in AAA
      patients.

PMID- 12010103
TI  - Aortoesophageal fistula secondary to mycotic thoracic aortic aneurysm:
      endovascular repair and transhiatal esophagectomy.
AB  - PURPOSE: To report a case of aortoesophageal fistula secondary to a mycotic
      thoracic aortic aneurysm (TAA) successfully repaired by stent-grafting of the
      descending thoracic aorta. CASE REPORT: A 66-year-old woman with a recent history
      of hemicolectomy for colon cancer complicated by postoperative infection
      presented with midthoracic pain, fever, hoarseness, and blood chemistries
      consistent with an inflammatory process. Imaging showed a widened mediastinum and
      displacement of the trachea due to a mycotic thoracic aneurysm; endoscopy
      confirmed a large fistula in the esophageal wall. There was no active bleeding,
      so an Excluder thoracic endograft was positioned in the aortic arch, partially
      covering the left subclavian artery origin. Three days later, a transhiatal
      esophagectomy was performed. Intravenous antibiotic therapy was continued for 6
      weeks. At 18 months, a minithoracotomy was performed because of extreme dyspnea.
      An aneurysm sac hygroma was drained in the thoracic cavity. At 2 years, the
      patient was well, and there were no signs of infection or dyspnea. CONCLUSIONS:
      Along with a transhiatal esophagectomy, we suggest that endovascular stent
      grafting has a place as a minimally invasive technique in the treatment of
      aortoesophageal fistula secondary to aneurysm of the thoracic aorta.

PMID- 12010104
TI  - Preventive stent placement for renal artery stenosis prior to emergent coronary
      artery bypass grafting.
AB  - PURPOSE: To illustrate the benefits of treating severe renal artery stenosis in
      renally compromised patients prior to surgery for coronary artery disease. CASE
      REPORT: A 63-year-old woman with unstable angina, severe coronary artery disease,
      and long-term severe renal impairment with a single functioning kidney underwent
      renal stent placement for high-grade renal artery stenosis prior to coronary
      artery surgery. The procedure improved her serum creatinine from 528 micromol/L
      at baseline to 385 micromol/L, and she subsequently underwent coronary artery
      bypass grafting without deterioration in her renal function. At 1 year, the
      patient has a serum creatinine of 400 micromol/L, and there is no evidence of in
      stent stenosis. CONCLUSIONS: Percutaneous renal angioplasty or stenting prior to
      coronary surgery in patients with concomitant renal and coronary artery disease
      may reduce perioperative renal deterioration in this specific group of patients.

PMID- 12010105
TI  - Hemorrhage from a right hepatic artery pseudoaneurysm: endovascular treatment
      with a coronary stent-graft.
AB  - PURPOSE: To report a novel case demonstrating the successful endovascular
      treatment of a right hepatic artery pseudoaneurysm using a balloon-expandable
      coronary stent-graft. CASE REPORT: A 60-year-old woman underwent surgical
      treatment for a Klatskin tumor, but her postoperative course was complicated by
      serious blood loss. An emergent celiac angiogram through a right transfemoral
      approach demonstrated a small iatrogenic pseudoaneurysm in the proximal right
      hepatic artery. A 7-F guiding catheter was positioned at the origin of the celiac
      trunk, and a Jostent coronary stent-graft mounted on a 2.7-F, 4-mm x 30-mm
      balloon catheter was successfully placed across the aneurysm neck. The final
      angiogram demonstrated total exclusion of the pseudoaneurysm with preservation of
      the arterial lumen. The hemodynamic condition of the patient became stable. At 12
      month follow-up, duplex scanning confirmed regular right hepatic artery patency
      and absence of thrombotic tissue or signs of infection around the stent-graft.
      CONCLUSION: For hepatic artery pseudoaneurysms, endovascular repair using small
      covered stents may be a viable alternative to transcatheter embolization. The use
      of coronary instruments facilitates treatment of vascular lesions in small
      caliber visceral vessels.

PMID- 12010106
TI  - Endovascular management of a pancreaticoduodenal aneurysm: a clinical dilemma.
AB  - PURPOSE: To report the successful endovascular embolization of a
      pancreaticoduodenal aneurysm (PDA). CASE REPORT: A 56-year-old man with a history
      of pancreatitis presented with insidious, progressive epigastric pain for the
      preceding 6 months. Contrast-enhanced computed tomography (CT) and selective
      hepatic digital subtraction angiography identified a 7.7-cm aneurysm that arose
      from the pancreaticoduodenal branch of the gastroduodenal artery. Through a
      percutaneous common femoral approach, 10 stainless steel coils were delivered to
      occlude the aneurysm. A single coil detached and became lodged in a small branch
      of the right hepatic artery without sequelae. At 26 months, duplex and CT scans
      show continued occlusion of the aneurysm. CONCLUSIONS: Transcatheter coil
      embolization should be the first choice treatment for aneurysms of the
      pancreaticoduodenal artery.

PMID- 12010107
TI  - Preoperative duplex-derived parameters and angioscopic evidence of valvular
      incompetence associated with superficial venous insufficiency.
AB  - PURPOSE: To determine if an association exists between duplex-derived parameters
      and intraoperative angioscopic findings of valvular incompetence. METHODS:
      Preoperative duplex scanning and intraoperative angioscopy were performed on 153
      limbs in 116 patients (84 women; mean age 53 years, range 24-79) with superficial
      venous incompetence (SVI). The duplex parameters of vein diameter at the
      saphenofemoral junction (SFJ), reflux duration, and peak retrograde reflux
      velocity at the SFJ were analyzed among SVI patients categorized by
      intraoperative angioscopy as type I (valves with elongated and atrophic cusps),
      type II (valves with expanded and depressed commissures with cusp changes), type
      III (cusps with other deformities), or type IV (absent valves). RESULTS: There
      were 33 limbs with type I valves, 56 with type II, 25 with type III, and 39 with
      type IV. Among the 89 limbs with type I or II valves, 64 (71.9%) had a peak
      velocity <30 cm/s, while only a quarter of the limbs with type III or IV values
      had a velocity <30 cm/s. The majority of patients with types I or II valves had a
      vein diameter <0.9 cm (25 [75.8%] type I and 37 [66.1%] type II). The
      sensitivity, specificity, and predictive value for identifying type I and II
      valve lesions were maximized at 90.0%, 66.7%, and 77.8%, respectively, when vein
      diameter <0.9 cm was combined with a peak reflux velocity >30 cm/s. CONCLUSIONS:
      These data suggest that a combination of variables determined by preoperative
      duplex scans may correlate to the severity of valvular deformity determined by
      direct angioscopic inspection.

PMID- 12010108
TI  - Preliminary experience with the Xtrak debulking device in the treatment of
      peripheral occlusions.
AB  - PURPOSE: To report our initial experience with a new rotary debulking device
      designed for treating long, diffusely diseased arterial segments. METHODS: Ten
      symptomatic patients (8 men; mean age 63 years, range 34-76) with occluded
      superficial femoral (n = 6) or popliteal (n = 4) arteries were enrolled into a
      study to evaluate the debulking capabilities of a rotational atherectomy device.
      Occlusion length ranged from 4.0 to 16.1 cm (mean 11.1 +/- 4.10). The occlusions
      were treated with a low-speed, over-the-wire rotary device featuring a flexible,
      spiral "corkscrew" that embeds itself in the obstructive material while a rotary
      cutting catheter simultaneously cuts and captures the obstruction in a single
      pass. RESULTS: The device cut and retrieved material in a single pass from all
      segments without device-related complications. The captured material consisted of
      a mixture of atherosclerotic plaque and thrombus. Minimum lumen diameters (MLD)
      increased from 0.0 to 2.2 +/- 1.09 mm (p<0.05) after Xtrak treatment and to 4.09
      +/- 1.20 mm (p<0.05) after adjunctive balloon dilation, which was used in 8 of 10
      segments. All patients improved clinically after the procedure, with an increased
      the mean ankle-brachial index sustained at 6 months (0.69 +/- 0.32, p<0.05
      compared to baseline and 1-month measurements). Six months after the procedure, 7
      patients remained free of clinical symptoms, while 3 patients required a
      subsequent intervention. CONCLUSIONS: These initial results demonstrate that the
      Xtrak device can safely debulk long segments of diffusely diseased arteries in a
      single pass while simultaneously retrieving the occluding material. Supplementary
      angioplasty may be required in the majority of cases. Larger studies are required
      to determine whether debulking followed by balloon dilation improves the long
      term prognosis in patients with chronic lower limb occlusions.

PMID- 12010109
TI  - Preliminary observations on the need for control angiography after peripheral
      endovascular brachytherapy using a centering balloon.
AB  - PURPOSE: To examine the need for completion angiography after endovascular
      femoropopliteal brachytherapy using a centering catheter. METHODS: Nine
      consecutive patients (7 men; mean age 68 years, range 53-79) were enrolled in a
      double-blinded multicenter randomized trial of endovascular brachytherapy after
      femoropopliteal balloon angioplasty. All patients underwent postdilation
      angiography, after which the centering catheter was placed in the dilated
      segment. The patients were randomized and transferred to the radiotherapy unit;
      the centering catheter was inflated only in patients randomized to receive
      brachytherapy (18 Gy of gamma radiation delivered to the target site 2 mm from an
      iridium-192 source axis). Because the local ethics committee required angiography
      after any interventional procedure (not stipulated in the study protocol), our
      patients were taken back to the angiosuite for angiography. RESULTS: There were
      no complications of angioplasty or centering catheter introduction. In the 5
      patients randomized to brachytherapy, the median inflation time of the centering
      catheter was 12.1 minutes (range 9.1-13.3). The completion angiogram following
      brachytherapy showed peripheral embolization in 2 patients and lesion recoil that
      required redilation in another; all the complications were confined to the
      treatment group. CONCLUSIONS: Three of 5 patients who received brachytherapy via
      a centering catheter demonstrated sequelae on postradiation angiography.
      Therefore, as in any other peripheral vascular intervention, completion
      angiography after brachytherapy seems to be essential in preventing delayed
      diagnosis of procedural complications.

PMID- 12010110
TI  - Covered stent to exclude intravascular thrombus.
AB  - PURPOSE: To describe the utility of stent-graft implantation to avoid distal
      embolization from a large thrombus-containing lesion. CASE REPORT: A 67-year-old
      man was evaluated for recent onset of disabling left leg claudication.
      Angiography disclosed a mobile lobular mass occluding the left common iliac
      artery; irregular staining suggested an atherothrombotic lesion. Through a
      percutaneous ipsilateral access and an 8-F sheath, a balloon-expandable Jostent
      peripheral stent-graft was positioned with the distal edge immediately proximal
      to the internal iliac artery ostium. A prominent "waist" at the center of the
      balloon confirmed entrapment of the thrombotic mass. Completion angiography
      showed an optimal result with no residual stenosis or evidence of distal
      embolization. At 6-month follow-up, the patient was asymptomatic with
      angiographically documented luminal patency and no evidence of in-stent stenosis.
      CONCLUSIONS: Stent-graft implantation appears a viable treatment alternative for
      thrombus-containing lesions, particularly when the thrombotic material is
      localized or is in a large vessel.

PMID- 12010111
TI  - Effects of abstinence-only education on adolescent attitudes and values
      concerning premarital sexual intercourse.
AB  - This article compares the values and attitudes of two groups of 7th and 8th grade
      adolescents toward premarital sexual activity. One group received state-funded,
      abstinence-only education; the other group did not receive that education.
      Abstinence-only education did not significantly change adolescents' values and
      attitudes about premarital sexual activity, nor their intentions to engage in
      premarital sexual activity. The majority of both the treatment and control group
      subjects expressed disagreement with the statement: "It is okay for people my age
      to have sexual intercourse," and they did not intend to have sexual intercourse
      while an unmarried teenager.

PMID- 12010112
TI  - Family-related correlates of sexually transmitted disease and barriers to care: a
      pilot study of pregnant African American adolescents.
AB  - This study explored associations between family-related measures and sexually
      transmitted disease (STD) history among 170 pregnant African American adolescent
      females, 14 to 20 years of age, attending prenatal care clinics in a large urban
      area of the South. Measures of low family support and infrequent mother-daughter
      communication were significant bivariate correlates of having at least one STD.
      Mother-daughter communication about preventing acquired immune deficiency
      syndrome remained significant in a multivariate model. The study also explored
      barriers to STD care-seeking behavior and found that few adolescents perceived
      access or financial issues as reasons to delay entry into the medical system. Low
      perceived family support was marginally associated with greater perceived
      barriers to STD care.

PMID- 12010113
TI  - Hepatitis B and C infections among homeless adolescents.
AB  - The lifestyle of homeless adolescents places them at high risk for contracting
      serious illnesses. This study sought to determine the hepatitis status and
      predictors of hepatitis infection among 150 homeless adolescents. Each
      participant took a psychosocial survey and provided a venous blood sample. Most
      respondents (95%) had engaged in sexual intercourse; approximately 36% indicated
      they had exchanged sex for food, shelter, or drugs. Youth reported a high rate of
      consistent condom use, however, 22% tested positive for hepatitis B or C.
      Homeless youth should be considered a high-risk group for hepatitis B or C virus
      infection. As hepatitis B vaccination programs have been targeted at school-based
      youth, most homeless youth are missed by these efforts. Targeted programs are
      needed to immunize this high-risk group.

PMID- 12010114
TI  - Promoting success for at-risk African-American youth: perceived barriers and
      resources in using community-based success criteria.
AB  - A Delphi technique was used to assess service provider and community consensus on
      program elements essential for promoting the success of at-risk African American
      youth. The respondent group consisted of 54 subjects representing three broad
      groups: service agencies, community leaders and members, and school system
      participants. The study identified barriers to the use of community-derived
      success constructs, opportunities for collaboration between community members and
      service agencies in the development of programs, and the feasibility of
      incorporating success constructs into program development and delivery. Although
      consensus was achieved on key issues, individual variations between counties
      point to the necessity of targeting intervention programs to the unique problems
      and expectations found in each community.

PMID- 12010115
TI  - Health risk behaviors among adolescents attending rural, suburban, and urban
      schools: a comparative study.
AB  - This study describes differences in health risk behaviors among 2,017 adolescents
      attending rural, suburban, and urban school districts in upstate New York.
      Differences in risk behaviors regarding use of tobacco, alcohol, and illegal
      substances; sexual activity; and carrying weapons were analyzed. A consistent
      pattern emerged from the analysis of the data, with rural students at most risk.
      The findings reinforce the need to focus on the relationship between residence
      and health risk behaviors, so that intervention programs specific to the needs of
      rural, suburban, and urban adolescents can be developed.

PMID- 12010116
TI  - Familial concordance of dietary fat practices and intake.
AB  - This study examined parent and child dietary fat practices and child dietary fat
      intake. High- and low-fat practices and percentage of kilocalories from fat were
      obtained from food records completed by 132 students in the 4th to 6th grades.
      Parents completed three scales: meat modifications (MMOD); fat substitutions
      (FSUB); and fruit, juice, and vegetable practices (FJVP). A parent low-fat
      practices (PLFP) scale was created with the items matching the child low-fat
      practices (LFPs). Parent PLFP, FSUB, and FJVP were significantly correlated with
      child LFPs. Parent LFP was a significant predictor of child LFP. Family
      intervention programs targeting dietary fat behaviors should encourage use of low
      fat dietary behaviors.

PMID- 12010117
TI  - The relationship of perceived benefits and barriers to reported exercise
      behaviors in college undergraduates.
AB  - This study examines current exercise habits and perceived benefits and barriers
      to exercise in a sample of 147 undergraduate university students. It found a
      significant relationship between perceived benefits and barriers to exercise and
      current exercise habits. Benefits most often associated with regular exercise
      habits relate to physical performance and appearance. Barriers most often
      associated with sporadic or nonexistent exercise habits relate to physical
      exertion and time constraints. A greater understanding of perceived benefits and
      barriers to exercise may assist health care providers and educators to establish
      methods for promoting exercise for the improved physical and mental health of a
      college-age population.

PMID- 12010120
TI  - A novel pressure-jump apparatus for the microvolume analysis of protein-ligand
      and protein-protein interactions: its application to nucleotide binding to
      skeletal-muscle and smooth-muscle myosin subfragment-1.
AB  - Reactions involving proteins frequently involve large changes in volume, which
      allows the equilibrium position to be perturbed by changes in pressure. Rapid
      changes in pressure can thus be used to initiate relaxation in pressure; however,
      this approach is seldom used, because it requires specialized equipment. We have
      built a microvolume (50 microl) pressure-jump apparatus, powered by a
      piezoelectric actuator, based on the original design of Clegg and Maxfield
      [(1976) Rev. Sci. Instrum. 47, 1383-1393]. This equipment can apply pressure
      changes of +/-20 MPa (maximally) in time periods as short as 80 micros and follow
      the resulting change in fluorescence signals. The system is relatively simple to
      use with fast (approx. 1 min) exchange of samples. In the present study, we show
      that this system can perturb the binding of 2'(3')-O-(N-methylanthraniloyl)-ADP
      to myosin subfragment-1(S1) from skeletal and smooth muscles. The kinetic data
      are consistent with previous work, and in addition show that, although 2'(3')-O
      (N-methylanthraniloyl)-ADP binds with a similar affinity to both proteins, the
      increase in molar volume for the skeletal-muscle S1 binding to ADP is half of
      that for the smooth-muscle protein. This high-volume change for smooth-muscle S1
      may be related to the ability of ADP to induce a 23 degrees tilt in the tail of
      S1 bound to actin.

PMID- 12010121
TI  - Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6
      glioma cells.
AB  - Stearoylethanolamide (SEA) is present in human, rat and mouse brain in amounts
      comparable with those of the endocannabinoid anandamide
      (arachidonoylethanolamide; AEA). Yet, the biological activity of SEA has never
      been investigated. We synthesized unlabelled and radiolabelled SEA to investigate
      its binding, degradation and biological activity in rat C6 glioma cells. We
      report that SEA binds to a specific site distinct from known cannabinoid or
      vanilloid receptors, and that AEA and capsazepine partly (approx. 50%)
      antagonized this binding. Treatment of C6 cells with SEA inhibits cellular nitric
      oxide synthase and does not affect adenylate cyclase, whereas treatment with
      cannabinoid type 1 agonist 2-arachidonoylglycerol activates the former enzyme and
      inhibits the latter. C6 cells also have a specific SEA membrane transporter,
      which is inhibited by NO, and a fatty acid amide hydrolase capable of cleaving
      SEA. In these cells, SEA shows pro-apoptotic activity, due to elevation of
      intracellular calcium, activation of the arachidonate cascade and mitochondrial
      uncoupling. NO further enhances SEA-induced apoptosis. Moreover, the cannabinoid
      type 1 receptor-mediated decrease in cAMP induced by AEA in C6 cells is
      potentiated by SEA, suggesting that this compound also has an 'entourage' effect.
      Taken together, this study shows that SEA is an endocannabinoid-like compound
      which binds to and is transported by new components of the endocannabinoid
      system. It seems noteworthy that degradation and pro-apoptotic activity of SEA
      are regulated by NO in a way opposite to that reported for AEA.

PMID- 12010122
TI  - Cysteine-less glycosylphosphatidylinositol-specific phospholipase C is inhibited
      competitively by a thiol reagent: evidence for glyco-mimicry by p
      chloromercuriphenylsulphonate.
AB  - Glycosylphosphatidylinositol (GPI)-specific phospholipases are highly valuable
      for studying the structure and function of GPIs. GPI-specific phospholipase C
      (GPI-PLC) from Trypanosoma brucei and phosphatidylinositol-specific phospholipase
      C (PI-PLC) from Bacillus cereus are the most widely studied of this class of
      phospholipases C. Inhibition of protein activity by thiol reagents is indicative
      of the participation of cysteine residues in biochemical events. The thiol
      reagent p-chloromercuriphenylsulphonate (pCMPS) inhibits T. brucei GPI-PLC, which
      has eight cysteine residues. Surprisingly, we found that the activity of B.
      cereus PI-PLC is also blocked by pCMPS, although the protein does not contain
      cysteine residues. Inhibition of B. cereus PI-PLC was reversed when pCMPS was
      size-separated from a preformed pCMPS.PI-PLC complex. In contrast, no activity
      was recovered when T. brucei GPI-PLC was subjected to a similar protocol.
      Equimolar beta-mercaptoethanol (beta-ME) reversed the inhibition of PI-PLC
      activity in a pCMPS.PI-PLC complex. For T. brucei GPI-PLC, however,
      ultrafiltration of the pCMPS.GI-PLC complex and addition of a large excess of
      beta-ME was necessary for partial recovery of enzyme activity. Thus T. brucei GPI
      PLC is susceptible to inactivation by covalent modification with pCMPS, whereas
      PI-PLC is not. Kinetic analysis indicated that pCMPS was a competitive inhibitor
      of PI-PLC when a GPI was a substrate. Curiously, with phosphatidylinositol as
      substrate, inhibition was no longer competitive. These data suggest that pCMPS is
      a glyco-mimetic that occupies the glycan binding site of PI-PLC, from where,
      depending on the substrate, it inhibits catalysis allosterically or
      competitively.

PMID- 12010123
TI  - Reaction of protein chloramines with DNA and nucleosides: evidence for the
      formation of radicals, protein-DNA cross-links and DNA fragmentation.
AB  - Stimulated phagocyte cells produce the oxidant HOCl, via the release of the
      enzyme myeloperoxidase and hydrogen peroxide. HOCl is important in bacterial cell
      killing, but excessive or misplaced generation can damage the host tissue and may
      lead to the development of certain diseases such as cancer. The role of HOCl in
      the oxidation of isolated proteins, DNA and their components has been
      investigated extensively, but little work has been performed on the protein-DNA
      (nucleosome) complexes present in eukaryotic cell nuclei. Neither the selectivity
      of damage in such complexes nor the possibility of transfer of damage from the
      protein to DNA or vice versa, has been studied. In the present study, kinetic
      modelling has been employed to predict that reaction occurs predominantly with
      the protein and not with the DNA in the nucleosome, using molar HOCl excesses of
      up to 200-fold. With 50-200-fold excesses, 50-80% of the HOCl is predicted to
      react with histone lysine and histidine residues to yield chloramines. The yield
      and stability of such chloramines predicted by these modelling studies agrees
      well with experimental data. Decomposition of these species gives protein
      derived, nitrogen-centred radicals, probably on the lysine side chains, as
      characterized by the EPR and spin-trapping experiments. It is shown that isolated
      lysine, histidine, peptide and protein chloramines can react with plasmid DNA to
      cause strand breaks. The protection against such damage afforded by the radical
      scavengers Trolox (a water-soluble alpha-tocopherol derivative) and 5,5-dimethyl
      1-pyrroline-N-oxide suggests a radical-mediated process. The EPR experiments and
      product analyses have also provided evidence for the rapid addition of protein
      radicals, formed on chloramine decomposition, to pyrimidine nucleosides to give
      nucleobase radicals. Further evidence for the formation of such covalent cross
      links has been obtained from experiments performed using (3)H-lysine and (14)C
      histidine chloramines. These results are consistent with the predictions of the
      kinetic model and suggest that histones are major targets for HOCl in the
      nucleosome. Furthermore, the resulting protein chloramines and the radicals
      derived from them may act as contributing agents in HOCl-mediated DNA oxidation.

PMID- 12010124
TI  - Isoprenoid biosynthesis in higher plants and in Escherichia coli: on the
      branching in the methylerythritol phosphate pathway and the independent
      biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate.
AB  - In the bacterium Escherichia coli, the mevalonic-acid (MVA)-independent 2-C
      methyl-d-erythritol 4-phosphate (MEP) pathway is characterized by two branches
      leading separately to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate
      (DMAPP). The signature of this branching is the retention of deuterium in DMAPP
      and the deuterium loss in IPP after incorporation of 1-[4-(2)H]deoxy-d-xylulose
      ([4-(2)H]DX). Feeding tobacco BY-2 cell-suspension cultures with [4-(2)H]DX
      resulted in deuterium retention in the isoprene units derived from DMAPP, as well
      as from IPP in the plastidial isoprenoids, phytoene and plastoquinone,
      synthesized via the MEP pathway. This labelling pattern represents direct
      evidence for the presence of the DMAPP branch of the MEP pathway in a higher
      plant, and shows that IPP can be synthesized from DMAPP in plant plastids, most
      probably via a plastidial IPP isomerase.

PMID- 12010125
TI  - Tumour metastasis suppressor, nm23-beta, inhibits gelatinase A transcription by
      interference with transactivator Y-box protein-1 (YB-1).
AB  - Gelatinase A transcriptional regulation is the consequence of combinatorial
      interactions with key promoter and enhancer elements identified within this gene.
      A potent 40 bp enhancer response element, RE-1, located in the near 5' flanking
      regions of the rat and human gelatinase A genes drives high-level expression in
      glomerular mesangial cells (MCs). Southwestern-blot analysis of MC nuclear
      extracts revealed specific interactions of RE-1 with at least four proteins, of
      which three have been identified as p53, activator protein 2 and the single
      stranded DNA-binding factor Y-box protein-1 (YB-1). In the present study, we
      report the identification of a fourth 17 kDa RE-1-binding protein as the rat
      homologue (nm23-beta) of the human nm23-H1 metastasis suppressor gene.
      Recombinant nm23-beta protein bound only the single-stranded forms of the RE-1
      sequence. Mutagenesis revealed direct interaction of nm23-beta with a repeat
      sequence, 5'-GGGTTT-3', shown previously to specifically interact with YB-1
      [Mertens, Harendza, Pollock and Lovett (1997) J. Biol. Chem. 272, 22905-22912],
      and recombinant nm23-beta protein competed for single-stranded YB-1 binding.
      Transient transfection of MC with an nm23-beta expression plasmid within the
      context of a RE-1/simian virus 40 promoter/luciferase reporter yielded a
      concentration-dependent repression (80-90%) of luciferase activity in MC and Rat1
      fibroblasts. A similar pattern of nm23-beta repression was demonstrated within
      the context of the RE-1/homologous gelatinase A promoter. Co-transfection of nm23
      beta blocked YB-1-mediated activation of transcription and expression of
      gelatinase A. Nm23-beta may be an important physiological regulator of gelatinase
      A transcription that acts by competitive interference with the single-stranded
      transactivator YB-1. Gelatinase A is a key mediator of tumour metastasis,
      suggesting that competitive suppression of transcription by nm23-beta (or the
      human nm23-H1) may be a component of the reduced metastatic capabilities of cells
      expressing high levels of this protein.

PMID- 12010126
TI  - A review of bacterial methyl halide degradation: biochemistry, genetics and
      molecular ecology.
AB  - Methyl halide-degrading bacteria are a diverse group of organisms that are found
      in both terrestrial and marine environments. They potentially play an important
      role in mitigating ozone depletion resulting from methyl chloride and methyl
      bromide emissions. The first step in the pathway(s) of methyl halide degradation
      involves a methyltransferase and, recently, the presence of this pathway has been
      studied in a number of bacteria. This paper reviews the biochemistry and genetics
      of methyl halide utilization in the aerobic bacteria Methylobacterium
      chloromethanicum CM4T, Hyphomicrobium chloromethanicum CM2T, Aminobacter strain
      IMB-1 and Aminobacter strain CC495. These bacteria are able to use methyl halides
      as a sole source of carbon and energy, are all members of the alpha
      Proteobacteria and were isolated from a variety of polluted and pristine
      terrestrial environments. An understanding of the genetics of these bacteria
      identified a unique gene (cmuA) involved in the degradation of methyl halides,
      which codes for a protein (CmuA) with unique methyltransferase and corrinoid
      functions. This unique functional gene, cmuA, is being used to develop molecular
      ecology techniques to examine the diversity and distribution of methyl halide
      utilizing bacteria in the environment and hopefully to understand their role in
      methyl halide degradation in different environments. These techniques will also
      enable the detection of potentially novel methyl halide-degrading bacteria.

PMID- 12010127
TI  - Wide bacterial diversity associated with tubes of the vent worm Riftia
      pachyptila.
AB  - We carried out a 16S rDNA-based molecular survey of the prokaryotic diversity
      associated with the chitin tubes of the giant vent tubeworm Riftia pachyptila
      (collected at the East Pacific Rise, 9 degrees N and 13 degrees N). Scanning
      electron microscopy showed dense microbial populations, particularly on the
      external surface of the middle and upper tube regions, which included very
      diverse prokaryotic morphotypes. We used archaeal- and bacterial-specific primers
      for polymerase chain reaction (PCR) amplification, but only bacterial amplicons
      were obtained. We analysed a total of 87 clones. Most belonged to the epsilon
      Proteobacteria, but also to the delta-, alpha- and gamma-Proteobacteria. A broad
      diversity of phylotypes belonging to other bacterial divisions was detected,
      including Verrucomicrobia, the Cytophaga-Flavobacterium-Bacteroides group and the
      candidate division OP8. We also retrieved a sequence, R76-B150, of uncertain
      phylogenetic affiliation, which could represent a novel candidate division. The
      sequence of the R. pachyptilagamma-proteobacterial endosymbiont was not detected.
      The bacterial diversity found suggests that complex metabolic interactions,
      particularly based on sulphur chemistry, may be occurring in different
      microniches of the R. pachyptila tubes.

PMID- 12010128
TI  - Rhizobial position as a main determinant in the problem of competition for
      nodulation in soybean.
AB  - Selected Bradyrhizobium japonicum strains inoculated on soybean seeds often fail
      to occupy a significant proportion of nodules when a competitor rhizobial
      population is established in the soil. This competition problem could result from
      a genetic/ physiological advantage of the adapted soil population over the
      introduced inoculant or from a positional advantage, as the soil population
      already occupies the soil profile where the roots will penetrate, whereas the
      inoculant remains concentrated around the seeds. Here, we have assessed the
      contribution of these factors with a laboratory model in which a rhizobial
      population is established in sterile vermiculite. We observed that the wild-type
      strain B. japonicum LP 3004 was able to grow in pots with N-free plant nutrient
      solution-watered vermiculite for six or seven generations with a duplication rate
      of at least 0.7 day(-1). In addition, the rhizobial population persisted for 3
      months with 10(6)-10(7) colony-forming units ml(-1) of the vermiculite-retained
      solution. N-starved, young rhizobial cultures are more efficient in performing
      several steps along their early association with soybean roots. However, N
      starvation during growth of rhizobia used for seed inoculation did not enhance
      their competitiveness against a 1 month vermiculite-established rhizobial
      population, which occupied more than 72% of the nodules. When a similarly
      established rhizobial population was recovered from the vermiculite and
      homogeneously suspended in plant nutrient solution, these cells were
      significantly less competitive (29% of nodules occupied) than rhizobia obtained
      from a fresh, logarithmic culture in a N-poor minimal medium, thus indicating
      that cell position rather than intrinsic competitiveness was the determinant for
      nodule occupation.

PMID- 12010129
TI  - The LysR-type regulator SftR is involved in soil survival and sulphate ester
      metabolism in Pseudomonas putida.
AB  - Sulphate esters make up a large proportion of the available sulphur in
      agricultural soils, and many pseudomonads can desulphurize a range of aryl- and
      alkylsulphate esters to provide sulphur for growth. After miniTn5 transposon
      mutagenesis of Pseudomonas putida S-313, we isolated 19 mutants that were
      defective in cleavage of the chromogenic sulphate ester 5-bromo-4-chloro-3
      indoxylsulphate (X-sulphate). Analysis of these strains revealed that they
      carried independent insertions in a gene cluster that comprised genes for a
      sulphate ester/sulphonate transporter (atsRBC) a LysR-type regulator (sftR), an
      oxygenolytic alkylsulphatase (atsK), an arylsulphotransferase (astA) and a
      putative TonB-dependent receptor (sftP). The SftP protein was localized in the
      outer membrane, and the arylsulfphotransferase was identified as an intracellular
      enzyme. Expression of sftR was repressed in the presence of inorganic sulphate,
      and the sftR gene was required for the expression of atsBC, atsRK and sftP-astA.
      An sftR mutant was unable to grow with aryl- or alkylsulphate esters in
      laboratory media and showed significantly reduced survival compared with the
      parent strain during incubation in Danish agricultural and grassland soils. This
      effect suggests that sulphate esters are an important sulphur source for microbes
      in aerobic soils and highlights the importance of the microbial population in the
      soil sulphur cycle.

PMID- 12010130
TI  - Effects of two different application methods of Burkholderia ambifaria MCI 7 on
      plant growth and rhizospheric bacterial diversity.
AB  - In order to acquire a better understanding of the effects of the different
      delivery modes of bacterial inoculants on plant growth and on the community
      structure of rhizosphere bacterial populations, Burkholderia ambifaria MCI 7
      (formerly B. cepacia MCI 7) was inoculated into the rhizosphere of maize plants
      by either seed adhesion or incorporation into soil. Plant growth was evaluated at
      different inoculum concentrations. The community structure of rhizosphere
      bacterial populations was evaluated by analysing the restriction patterns of the
      DNA coding for 16S rRNA amplified by polymerase chain reaction (PCR) (ARDRA) of
      745 bacterial isolates. A number of diversity indices (richness, Shannon
      diversity, evenness and mean genetic distance) were calculated for each bacterial
      population isolated from control and treated plants according to the concept of
      the r/K strategy. Moreover, the analysis of molecular variance (AMOVA) method was
      applied to estimate the genetic differences among the various bacterial
      populations. Our results showed that the method of application can be an
      essential element in determining the effects of the inoculant on plant growth. In
      fact, when applied as a maize seed treatment, B. ambifaria MCI 7 promoted plant
      growth significantly; on the contrary, when incorporated into soil, the same
      strain reduced plant growth markedly. As far as the bacterial community structure
      is concerned, B. ambifaria MCI 7 affected the indigenous microflora of treated
      plants according to the application method: seed treatment brought about an
      abrupt decrease in bacterial diversity, whereas incorporation into soil increased
      bacterial diversity. Moreover, changes in bacterial diversity were limited to r
      strategist bacteria. In conclusion, B. ambifaria MCI 7 can act as both a plant
      growth-promoting rhizobacterium and a deleterious rhizobacterium depending on the
      inoculation method.

PMID- 12010136
TI  - Short- and long-term success of organs transplanted from acute methanol poisoned
      donors.
AB  - BACKGROUND: The shortage of organs for transplantation has made it necessary to
      extend the criteria for the selection of donors, among others including those
      patients who die because of toxic substances such as methanol. Methanol is a
      toxic which is distributed through all the systems and viscera of the organism
      and tends to cause a severe metabolic acidosis. It can specifically cause serious
      or irreversible lesions of the central nervous system (CNS) and retina, and
      ultimately brain death. We present our experience with 16 organ donors who died
      as a result of acute methanol intoxication in 10 Spanish hospitals over the last
      14 yr. PATIENTS AND METHODS: Between October 1985 and July 1999, 16 organ donors
      with brain death caused by acute methanol intoxication, 13 females and three
      males with a mean age of 38.4 +/- 7.6 yr (interval: 26-55 yr), allowed 37
      elective transplants to be performed: 29 kidneys, four hearts and four livers for
      37 recipients, and one urgent liver transplantation to a recipient with fulminant
      hepatitis. RESULTS: The immediate postoperative period was favourable for the 38
      graft recipients. None of the graft recipients presented gap anion metabolic
      acidosis in the immediate postoperative period, nor symptomatology or lesions of
      the CNS characteristic of methanol intoxication. Two patients died during the
      first month post-transplantation, a liver recipient and a heart recipient, at 16
      and 24 days, respectively, because of acute rejection of the graft. At 1 month
      after transplantation 35 of the 36 recipients had been discharged from hospital
      with normal-functioning grafts. The last of the recipients, a kidney recipient,
      was discharged at 6 wk with normal-functioning graft. Actuarial survival of the
      graft and patient of kidney recipients at 1, 3 and 5 yr was 92.6, 77.8, and 75%,
      and 100, 88.9 and 83.3%, respectively; with average serum creatinines of 139.9 +/
      42.9, 150.4 +/- 42.8, and 164.4 +/- 82.5 micromol/L, respectively. At 1 yr after
      transplantation the three heart recipients and two of the three liver recipients
      had normal-functioning graft. CONCLUSIONS: Methanol intoxication is not
      transferred from the donor to the recipient. The survival of the graft and
      kidney, heart and liver recipients using organs from donors who die because of
      methanol does not differ in the short- and long-term from the transplants
      performed with organs from donors who die from other causes.

PMID- 12010137
TI  - Upper gastrointestinal complications after renal transplantation: a 3-yr
      sequential study.
AB  - BACKGROUND: Upper gastrointestinal complications have historically resulted in
      considerable morbidity and mortality to renal transplant recipients. Over the
      last decade, antiulcer prophylaxis with proton-pump inhibitors and
      immunosuppression with tacrolimus-based regimes have been introduced. Little has
      been written about foregut complications after renal transplantation since the
      use of these agents. The aim of this study was to compare the frequency of upper
      gastrointestinal complications after renal transplantation in patients treated
      with (i) omeprazole vs. ranitidine, and (ii) tacrolimus vs. cyclosporin based
      immunosuppression. METHODS: Information on 236 patients undergoing renal
      transplantation between January 1996 and December 1998 was collected
      prospectively onto a computerized database. RESULTS: Overall, 20 patients (8%)
      developed upper gastrointestinal complications, opportunistic infections
      accounted for 9/20 (45%). No patient developed gastroduodenal ulceration,
      required laparotomy, suffered graft loss or died. There was no significant
      difference in the frequency of complications between patients that received
      antisecretory therapy with omeprazole (9/118, 8%) and those that received
      ranitidine (11/118, 9%), nor between those that were on tacrolimus (7/101, 7%)
      and those on cyclosporin (13/135, 10%) based immunosuppression regimes. Patients
      that developed foregut complications were significantly older than those not
      developing complications (mean age 50 vs. 43 yrs, p=0.05). Further, patients that
      developed opportunistic infections were more frequently diabetic than those in
      whom opportunistic infections were not seen (4/31, 13% vs. 5/205, 2%), p=0.02.
      CONCLUSIONS: We observed a low frequency (8%) of upper gastrointestinal tract
      complications after renal transplantation. There was no difference in the
      frequency of complications between patients on tacrolimus and those on
      cyclosporin based immunosuppression. Furthermore, the complication rates were
      similar in those that received omeprazole and those that received ranitidine as
      antiulcer prophylaxis, indicating the equivalence of these two agents in this
      setting.

PMID- 12010138
TI  - Neoral rescue therapy in transplant patients with intolerance to tacrolimus.
AB  - BACKGROUND: The calcineurin inhibitors, cyclosporine and tacrolimus, are the
      mainstay of current immunosuppressive regimens for the prevention of acute
      rejection in organ transplantation. The choice of the individual agent used often
      depends on the preference of the Transplant Center and patient type. Adverse
      effects associated with tacrolimus may impact its clinical utility in many
      patients. This study characterizes the clinical outcomes of transplant recipients
      who experienced adverse effects from tacrolimus and were converted to
      cyclosporine-microemulsion-based (Neoral([cyclosporine, USP] MODIFIED) therapy.
      METHODS: Hepatic or renal allograft recipients unable to maintain adequate
      immunosuppression with a tacrolimus-based regimen for reasons of toxicity or
      efficacy were recruited for this study and converted to cyclosporine
      microemulsion-based therapy. Data were collected on drug dosing, trough
      concentrations, and treatment duration, as well as detailed information on
      tacrolimus-associated toxicities that prompted rescue with cyclosporine
      microemulsion. Furthermore, clinical and laboratory data related to the clinical
      course of the patients after conversion to cyclosporine-microemulsion were
      recorded for up to 1 yr following conversion. RESULTS: One hundred and fifty
      seven transplant recipients were enrolled in this study. Predominant reasons for
      discontinuation of tacrolimus were neurotoxicity (55%), diabetes (24%),
      nephrotoxicity (15%), and gastrointestinal intolerance (24%). Patients frequently
      had multiple symptoms prompting rescue therapy with cyclosporine-microemulsion.
      Over 70% of subjects had improvement or resolution of their tacrolimus-associated
      adverse symptoms within 3 months post-conversion. Acute rejection episodes
      occurred in 27% of patients converted to cyclosporine-microemulsion. CONCLUSIONS:
      Cyclosporine-microemulsion rescue therapy in patients experiencing adverse
      clinical effects associated with tacrolimus is an effective treatment option
      which leads to resolution of these adverse effects in the majority of patients,
      and allows for satisfactory clinical outcomes.

PMID- 12010139
TI  - The effect of angiotensin converting enzyme gene polymorphism on chronic
      allograft dysfunction in living donor renal transplant recipients.
AB  - BACKGROUND: Chronic allograft dysfunction (CAD), the major cause of the failure
      of kidney allografts, may be caused by immunological and non-immunological
      haemodynamic factors. Renin-angiotensin system has been implicated in the
      development of intraglomerular hypertension and has a central role on progression
      in chronic renal disease. Polymorphism in 16th intron of the ACE gene has been
      reported to predict the circulating angiotensin II levels. The aim of this study
      was to investigate the effect of the both recipient and donor angiotensin
      converting enzyme (ACE) genotype on the development of CAD in renal allograft
      recipients. PATIENTS AND METHODS: A total of 143 renal transplant recipients (95
      male, 48 female, mean age 32 +/- 10 yr) were included. In order to exclude the
      effect of cold ischaemia, only patients transplanted from living donors were
      selected. Factors analysed in the development of CAD were donor and recipient
      age, past history of acute rejection, presence of hypertension and
      hypercholesterolaemia, serum uric acid level and ACE gene polymorphism. RESULTS:
      Forty of the patients (28%) had CAD. Homozygous deletion type ACE gene
      polymorphism was detected in 59 renal transplant recipients (42%) and in 31
      donors of the patients (37%). On comparing patients with and without CAD, donor
      age, rate of acute rejection and hypertension and serum uric acid levels were
      significantly higher in CAD (+) groups. Neither recipient nor donor ACE genotype
      was associated with time to CAD. Cox regression analysis revealed donor age (p <
      0.001), presence of hypertension (p=0.002) and serum uric acid levels (p=0.009),
      but neither donor nor recipient ACE genotype as independent factors for
      predicting development of CAD. CONCLUSION: Donor age, presence of hypertension
      and serum uric acid levels was independent factors. Donor and recipient ACE
      genotype seemed to have no influence on the development of CAD in living donor
      transplanted patients.

PMID- 12010140
TI  - Organ donation in Hawaii: impact of the final rule.
AB  - BACKGROUND: In an effort to increase organ donation, the Department of Health and
      Human Services issued the Final Rule in 1998. The Health Care Financing
      Administration (HCFA) later required hospitals to notify organ procurement
      organizations (OPO) of all deaths and imminent deaths in order to remain eligible
      for Medicare and Medicaid reimbursement. We set out to determine the impact of
      the Final Rule on organ donation in Hawaii. METHODS: Medical records of all
      deaths between January 1999 and December 2000 at 17 acute-care hospitals were
      reviewed to determine the number of medically suitable, potential organ donors.
      RESULTS: Of 9427 deaths, 144 were potential organ donors. In 1999, before the
      Final Rule, 60 of 75 (80%) potential donors were identified and 40 (53%) were
      referred to the OPO. In 2000, after the Final Rule, the identification rate was
      83% and the referral rate was 70%. CONCLUSIONS: Although, the Final Rule
      increased the referral rate slightly, medical centres must continue to improve
      their identification of potential donors and prompt referral. This is not only to
      comply with the Final Rule, but ultimately to increase organ donation to meet the
      needs of the ever-expanding list of patients waiting for organs.

PMID- 12010141
TI  - The oxidative metabolism of polymorphonuclear neutrophils in pediatric liver
      graft recipients.
AB  - BACKGROUND: Data on the oxidative metabolism of polymorphonuclear neutrophils
      (PMN) after solid organ transplantation are very limited. We hypothesized that
      immunosuppressive agents reduce the capacity of PMN to produce reactive oxygen
      species, such as O2(-), H2O2, OH, and OCL(-) leading to an increased
      susceptibility to infectious complications after liver transplantation. METHODS:
      A lucigenin-enhanced chemiluminescence (CL) assay was used with soluble and
      particulate stimuli to study the oxidative metabolism of PMN in pediatric liver
      graft recipients. Sixteen patients (median age: 2.4 yr) were enrolled in a
      prospective study and integrated CL response was compared with the CL activity of
      29 healthy controls. RESULTS: In the second week post-transplant, we found a
      significantly reduced CL activity. Pre-operatively, and after lowering steroids
      and cyclosporin A (CsA) the oxidative burst was normal. CONCLUSIONS: Our data
      suggest that CsA and steroids may not only influence T and B cells but also PMN,
      which may be a relevant factor for the incidence of infectious complications in
      pediatric liver graft recipients.

PMID- 12010142
TI  - Calcineurin inhibitor nephrotoxicity: reduction in dose results in marked
      improvement in renal function in patients with coexisting chronic allograft
      nephropathy.
AB  - BACKGROUND: Calcineurin inhibitors (CNI) have significantly reduced the incidence
      of acute rejection. Nephrotoxicity however, may contribute to long-term allograft
      dysfunction. METHODS: Forty-six biopsies from patients who had been transplanted
      for more than 6 months were examined. Sixteen biopsies had evidence of chronic
      allograft nephropathy (CAN) alone, 21 biopsies had evidence of coexisting CAN in
      addition to histological evidence of calcineurin inhibitor nephrotoxicity (CNIN)
      while nine had neither evidence of nephrotoxicity nor CAN. Patients with evidence
      of nephrotoxicity underwent a reduction in dose of CNI while those with CAN alone
      had no change in therapy. Renal function was followed for a mean of 17.4 months
      after biopsy. RESULTS: The serum creatinine at the time of diagnostic renal
      biopsy was comparable between those with CAN alone (mean 0.25 +/- 0.18 mmol/L)
      and those with coexisting CNIN (mean 0.23 +/- 0.05 mmol/L, p=0.33). The patients
      with CNIN however, had a rapid improvement in renal function within 1 month after
      dose reduction. This was sustained for the duration of follow-up (mean serum
      creatinine 0.162 +/- 0.038 mmol/L at 1 yr after dose reduction; p=0.001). In
      comparison, those with CAN alone had a gradual decline in renal function with a
      serum creatinine at 1 yr after biopsy of 0.31 +/- 0.187, p=0.01. CONCLUSION:
      Reduction in the dose of CNI in those with histological evidence of
      nephrotoxicity resulted in a sustained improvement in renal function.

PMID- 12010143
TI  - Mycophenolic acid concentrations in long-term heart transplant patients:
      relationship with calcineurin antagonists and acute rejection.
AB  - BACKGROUND: When used in conjunction with steroids and cyclosporin, mycophenolate
      mofetil (MMF) has been shown to significantly reduce mortality and incidence of
      rejection in the first year after heart transplantation. It also appears that in
      this early post-transplantation period, the monitoring of immunosuppressive
      therapies may be warranted. The current study was undertaken to determine if such
      monitoring is still useful more than 1 yr after heart transplantation. METHODS:
      Twenty-six patients who had survived the first year after orthotopic heart
      transplantation and had been on MMF therapy for more than 3 months were
      prospectively followed. At the time of their routine endomyocardial biopsy blood
      samples were taken to monitor immunosuppressive therapy. Most patients had two
      samples taken, on average 109 d apart. RESULTS: There were 22 episodes of
      asymptomatic rejection documented on a total of 48 biopsies. Of these, only two
      were of ISHLT (International Society for Heart and Lung Transplantation) grade 3A
      the remainder being of ISHLT grades 1 or 2. There was no relation between
      immunosuppressive regimen (tacrolimus and MMF or cyclosporin and MMF) and
      rejection. There was no relation between monitored immunosuppressive levels and
      rejection. Patients with the combination of MMF and tacrolimus had significantly
      higher plasma mycophenolic acid levels despite significantly lower daily MMF
      dose. CONCLUSION: There does not appear to be a benefit in continued monitoring
      of plasma mycophenolic acid levels beyond the first year of heart
      transplantation. There were significant differences in plasma mycophenolic acid
      levels depending on the type of calcineurin inhibitor concomitantly used.

PMID- 12010144
TI  - Angiotensin-II receptor antagonist losartan reduces microalbuminuria in
      hypertensive renal transplant recipients.
AB  - In recent years, it has been demonstrated that losartan lowers macroproteinuria
      in diabetic or non-diabetic renal transplant recipients (RTx) similar to
      angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may
      reflect subclinical hyperfiltration damage of the glomerulus. It could be a
      marker of kidney dysfunction in renal transplantation. The aim of the study was
      to assess the efficacy of losartan in hypertensive RTx with MAU. This study was
      conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical
      treatment of the patients. All cases received 50 mg/day losartan therapy for 12
      wk. Renal functions and MAU were determined 12 and 6 wk and just before the
      treatment as well as sixth and twelfth week of the treatment in all patients.
      Losartan satisfactorily lowered systemic blood pressure. A significant reduction
      in MAU was observed from 103 +/- 53 microg/min at the beginning to 59 +/- 25
      microg/min in the sixth week and 47 +/- 24 microg/min in the twelfth week
      (p=0.0007 and 0.0005, respectively). From the sixth week of the treatment, the
      therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but
      did not change mean leukocyte and platelet counts, urea, creatinine levels and
      creatinine clearances. No serious side-effect was observed during the study. In
      conclusion, we found that losartan decreased MAU in hypertensive RTx. For that
      reason, it might be considered as the first choise antihypertensive agent for the
      renoprotection in selected patients.

PMID- 12010145
TI  - Liver preservation with HTK: salutary effect of hypothermic aerobiosis by either
      gaseous oxygen or machine perfusion.
AB  - The aim of the present study was to improve the viability of marginal livers from
      non-heart beating donors upon cold preservation using two different techniques
      for the provision of tissue aerobiosis. Livers from male Wistar rats (250-300 g
      bw) were harvested after 60 min of cardiac arrest, flushed via the portal vein
      with 20 mL of heparinized Ringer's solution and 60 mL of histidine-tryptophan
      ketoglutarate (HTK) preservation solution. Control livers were then stored
      submerged in HTK for 24 h at 4 degrees C while other organs were subjected to
      aerobic conditions by either insufflation of gaseous oxygen via the venous
      vascular system of the cold stored organ (VSOP) or pulsatile machine perfusion
      (MP) with oxygenated HTK at 5 mL/min at 4 degrees C. Superoxide dismutase (SOD)
      (7500 IU) was added to the last 10 mL of HTK in order to prevent adverse effects
      of high oxygen tensions at hypothermia. Viability of the livers was assessed upon
      isolated perfusion in vitro with oxygenated Krebs-Henseleit buffer at constant
      flow. VSOP or MP, both significantly improved vascular conductivity upon
      reperfusion as evaluated by portal venous pressure, reduced hepatic enzyme
      release and led to a rise in hepatic bile production upon reperfusion. Induction
      of apoptosis was also looked for in tissue homogenates by Western analysis for
      cleavage of poly(ADP-ribose)polymerase (PARP). Expression of cleaved PARP
      fragment could be found in reperfused control livers but also, though to a lesser
      extend, after VSOP or MP. In conclusion, provision of oxygen during cold
      preservation significantly contributes to improve organ viability upon
      reperfusion and must be regarded as a useful adjunct for marginal or pre-damaged
      livers. HTK has been shown for the first time to be also suitable for long-term
      MP preservation of the liver, but, as inferred from these data, simple
      insufflation of gaseous O2 may be considered a feasible alternative.

PMID- 12010146
TI  - Diarrhoea following renal transplantation.
AB  - In this study, we retrospectively evaluated all attacks of diarrhoea in our renal
      transplant recipients that came to our medical attention between 1985 and 2000.
      Also, the clinical features of patients with diarrhoea were compared with the
      features of recipients without diarrhoea. We diagnosed 41 attacks of diarrhoea in
      39 (12.6%) of 308 renal transplant recipients during this time period. An
      aetiology was detected in 33 (80.5%) of all diarrhoeal episodes and in seven
      (17.1%) of those the specific agent was diagnosed with the help of stool
      microscopy. The most frequent causes of diarrhoeal attacks were infectious agents
      (41.5%) and drugs (34%). Six (14.6%) episodes of diarrhoea were chronic and six
      were nosocomial. About two-thirds of diarrhoea developed within the late post
      transplant period (>6 months). When recipients with diarrhoea were compared with
      those without diarrhoea, it was seen that diarrhoeal patients had significantly
      higher creatinine and significantly lower albumin levels when compared with the
      latter group (p < 0.05). Also, the frequency of antibiotic usage was
      significantly higher in diarrhoeal patients than in the control group (p < 0.05).
      Four (10.2%) patients with diarrhoea died despite institution of the appropriate
      therapy. Two of these deaths were primarily related to diarrhoea and the
      aetiological agent was Clostridium difficile in both these cases. During the 15
      yr study period, 3.6% of all deaths and 5.1% of infection-related deaths in
      transplant recipients were secondary to diarrhoea. As a result, we observed that
      infections and drugs were the most frequent causes for diarrhoea in our series of
      renal transplant recipients. Also, diarrhoea was an important cause of mortality
      in this patient population.

PMID- 12010147
TI  - Should moderate acute rejection of a cardiac transplant graft be treated?
AB  - Histologically proven, moderate acute rejection after orthotopic heart
      transplantation (OHT) is commonly treated with intravenous steroids. This regimen
      may result in severe metabolic and infectious side-effects. The purpose of this
      study was to assess and compare outcomes in treated (T) versus not treated (N-T)
      biopsy proven 3A rejection episodes in cardiac transplant recipients. METHODS: A
      retrospective analysis was conducted to identify all biopsy proven 3A rejection
      episodes that occurred over the time period 1995-2000 in patients (patients) >or=
      6 months after OHT (n=48 episodes in 35 patients). Of the 48 episodes, 19 were N
      T and 29 were T. Decision to treat 3A rejection was based on time after
      transplant, haemodynamic and/or clinical compromise and left ventricular (LV)
      dysfunction measured by 2D echo. Most N-T episodes received an increase in
      background immunotherapy. RESULTS: Time from transplant to index 3A episode in N
      T patients was 4.2 versus 2.7 yr for the T patients (p=0.06). There were no
      differences seen between T and N-T groups for the first and second post-3A biopsy
      results or LV function post-3A. Presence of coronary disease or death were not
      different between groups. Of the 29 patients with T episodes, no differences in
      outcomes (death, first and second post-3A biopsy score, coronary disease,
      myocardial infarction, or LV function) were seen based on use of treatment with
      intravenous versus oral steroid. CONCLUSION: In patients more than 6 month after
      OHT, there were no differences in outcomes (ongoing rejection or LV function)
      between N-T episodes of 3A rejection and T episodes. In T patients the use of
      oral steroids was equally as effective for treatment of 3A episodes as
      intravenous steroids.

PMID- 12010148
TI  - Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia.
AB  - OBJECTIVE: To analyse the outcome of six children with Crigler-Najjar syndrome
      type I (CNS-I) and report the first three living-related liver transplants for
      this syndrome in Saudi Arabia and the Middle East. SETTINGS: To review the
      medical records of six children suffering from CNS-I, three of whom underwent
      living-related liver transplantation (LRLT) between 22 November 1998 and January
      2001. MAIN RESULTS: Living-related liver transplantation was performed in three
      children with a pre-transplant unconjugated bilirubin level of 362, 381 and 502
      micromol/L, respectively, despite daily phototherapy of >or= 12 h. Two of the
      transplanted children developed acute hepatocellular rejection, which was
      successfully treated with methylprednisolone pulse therapy. One tested
      cytomegalovirus positive (using the PP65 method), but showed no signs of clinical
      infection and was treated with ganciclovir. One patient had a biliary leak at the
      cut surface of the graft which was surgically repaired. Post-operative bilirubin
      levels returned to normal in all three transplanted children and no further
      phototherapy was required. One patient, who was not transplanted but received
      phototherapy, developed severe neurological damage prior to the start of our
      living-related liver transplant programme with a bilirubin level of 450
      micromol/L, her sister is still awaiting transplantation. A 14-yr-old child with
      a bilirubin level of 420 micromol/L is presently undergoing phototherapy whilst
      awaiting orthotopic liver transplantation because of the lack of a suitable
      living-related donor. Six siblings of the six children in our series were
      reported dead by the families. CONCLUSION: Crigler-Najjar syndrome type I is a
      relatively common disease in Saudi Arabia for which LRLT is a curative treatment
      when performed at an early age before the development of kernicterus and
      neurological deficiency. In countries where there is a severe shortage of
      cadaveric organs, as is the case in Saudi Arabia, LRLT is the optimum treatment
      modality for this syndrome.

PMID- 12010149
TI  - Hepatic copper concentration in children undergoing living related liver
      transplantation due to Wilsonian fulminant hepatic failure.
AB  - Liver transplantation is indicated for Wilson's disease (WD) patients having the
      fulminant form and end-stage liver failure. To evaluate whether living related
      liver transplantation (LRLT) can correct the copper metabolism in WD patients, we
      studied two children who underwent LRLT because of fulminant hepatic failure.
      They were 7 and 13 yrs old at the time LRLT was performed. Serum ceruloplasmin
      levels, serum copper levels, copper urine excretion, and hepatic copper
      concentrations were measured. Serum ceruloplasmin levels (16.7 +/- 1.2 mg/dL) and
      serum copper levels (67.0 +/- 1.4 microg/dL) were lower than the normal range
      after LRLT in case 1. In both patients, urinary copper excretion was reduced
      markedly after LRLT, but was not normalized (case 1, 191.2 +/- 182.2 microg/d;
      case 2, 140.0 +/- 156.7 microg/d). Hepatic copper concentrations were slightly
      elevated (case 1, 158.8 +/- 44.6 microg/g dry weight; case 2, 147.0 microg/g dry
      weight) after LRLT in both cases, but did not exceed 250 microg/g dry weight.
      LRLT is a curative procedure in Wilson's disease presenting fulminant hepatic
      failure or advanced cirrhosis. However, this study indicates that the conditions
      of copper metabolism in WD patients undergoing LRLT are similar to those in
      heterozygous genetic carriers. Because the living related donors are the parents
      who carry the abnormal gene, LRLT cannot completely restore the copper balance in
      WD patients.

PMID- 12010150
TI  - Atelectasis--an unusual and late complication of lung transplant.
AB  - We report a previously unrecognized late complication of allograft lung
      transplantation - persistent recurrent atelectasis of the transplanted lung. The
      patient developed sudden, severe respiratory distress about 2 yr after a right
      lung transplant, because of acute atelectasis of her transplanted lung. Multiple
      transbronchial biopsies at the time revealed minimal inflammation and no evidence
      of rejection. She was treated with surfactant replacement therapy, and her
      collapsed lung fully expanded following surfactant installation. To eliminate the
      possibility of acquired deficiency of surfactant lipids or proteins,
      ultrastructural examination and immunostains for surfactant proteins were
      performed in a transbronchial lung biopsy. No deficiency of surfactant lipids or
      proteins was found. On ultrastructural examination of the lung biopsy, the number
      of Type II cells per alveolus and the number of lamellar bodies per square micron
      of Type II cell cross-sectional area was increased compared with an age-matched
      control. We conclude that synthesis of surfactant lipids and proteins was
      unimpaired and because of the patient's response to surfactant replacement
      therapy, that the increase in number of lamellar bodies could reflect a
      compensatory mechanism for a surfactant functional defect. The patient later
      developed breast carcinoma to which she succumbed. We raise the possibility that
      the functional surfactant defect is a hitherto unrecognized non-metastatic
      manifestation of malignancy.

PMID- 12010151
TI  - Living related liver transplantation for recurrent hepatocellular carcinoma in a
      normal liver.
AB  - The role of liver transplantation for hepatocellular carcinoma (HCC) is evolving.
      In patients with advanced liver disease and early stage HCC, transplantation
      offers the best hope for cure. A living donor offers the optimal approach to a
      timely transplant, before disease progression obviates the potential benefit. But
      extending the indications beyond those designated by the United Network for Organ
      Sharing (UNOS) for liver transplantation for HCC is controversial [Hepatology
      2001: 33: 1073; Liver Transplant 2000: 6: S1]. Cadaver split techniques and use
      of living donors are potentially compelling ways to test the limitations of liver
      transplantation for HCC, without notably reducing the cadaver organ pool. Herein,
      we report a rare case of a patient who developed a well-differentiated HCC in a
      normal liver. After resection of the index lesion and, later, of a remote
      recurrent lesion, a living donor liver transplant was offered. The natural
      history of this lesion and the management of transplantation in this setting are
      discussed.

PMID- 12010152
TI  - Elastase, alpha2-macroglobulin and alkaline phosphatase in crevicular fluid from
      implants with and without periimplantitis.
AB  - The aim of this investigation was to determine the presence of selected enzymes
      and enzyme inhibitors in crevicular fluid collected from implants with and
      without clinical, radiographic and microbiological signs of periimplantitis.
      Eleven implants with symptoms of periimplantitis in eight patients (four men and
      four women) were compared to eleven implants in seven subjects (one man and six
      women) without periimplantitis. Periimplant crevicular fluid (PICF) was collected
      at the mesial and distal sites of each implant. Alkaline phosphatase activity
      (ALP) was measured by using p-nitrophenyl-phosphate as substrate, elastase
      activity (EA) by the use of a low molecular weight fluorogenic substrate, and the
      inhibitor alpha2-macroglobulin (alpha2M) by ELISA. ALP, EA and alpha2M were
      detected in the majority of samples in both groups. In comparison to the
      clinically healthy implants, total amounts of each of these substances were
      significantly higher in PICF collected around implants with periimplantitis. The
      mean total amounts of EA, alpha2M and ALP in the healthy group were: EA: 1.8 ng,
      alpha2M: 3.1 ng, ALP: 24.1 U, and in the periimplantitis group EA: 23.1 ng,
      alpha2M: 25.2 ng and ALP: 142.3 U. In addition, all three mediators were
      correlated with the clinical parameters. The results confirm the similarity of
      the inflammatory response of tissues surrounding implants and natural teeth, and
      suggest that ALP and EA could be promising markers of bone loss around dental
      implants.

PMID- 12010153
TI  - Implant osseointegration in the irradiated mandible. A comparative study in dogs
      with a microradiographic and histologic assessment.
AB  - This research focuses on the effects of radiotherapy on the osseointegration of
      dental implants placed before or after radiotherapy in 11 male beagles. After the
      extraction of all mandibular premolars 1st and 2nd molars, three dogs were
      implanted without radiotherapy (Control group), four dogs were irradiated 4 weeks
      after implantation (IrA group) and four dogs were irradiated 8 weeks before
      implantation (IrB group). Eight implants were placed in each dog, in an
      alternating pattern: four nonsubmerged ITI Bonefit titanium plasma spray-coated
      and four submerged Steri-Oss hydroxyapatite-coated. The irradiated dogs received
      4.3 Gy daily for 10 days. Two different fluorescent markers were administered at
      the time of implantation and of irradiation. The dogs were sacrificed 6 months
      after implantation, i.e. 5 months after radiotherapy for the IrA group and 8
      months for the IrB group. Each mandible was submitted to histological and
      microradiographic analysis. Bone formation occurred around 85 of the 88 implants
      and consisted mostly of the successive deposit of woven and lamellar bone. Both
      irradiated groups showed obvious bone remodeling in alveolar bone as well as in
      the basilar part of the mandible. Nevertheless, in the IrA group, the resorption
      phenomena predominated over osteogenesis. The balance between these two opposite
      processes seemed to be restored 8 months after the end of radiotherapy (IrB
      group). In spite of focal lesions of radiation-specific bone destruction
      emphasized in some irradiated dogs, we conclude from our results that
      osseointegration of dental implants is possible in irradiated bone tissue.

PMID- 12010154
TI  - Difference in penetration of horseradish peroxidase tracer as a foreign substance
      into the peri-implant or junctional epithelium of rat gingivae.
AB  - Horseradish peroxidase (HRP) tracer was applied to the gingival sulcus of
      implants or natural teeth at 5, 25, or 50 mg/ml to investigate the sealing
      capacities of the peri-implant epithelium (PIE) and junctional epithelium (JE);
      the extent of HRP penetration was observed under electron microscopy. A Ti-6Al-4V
      implant was inserted either immediately (immediate implantation) or 2 weeks
      (delayed implantation) after extraction of the maxillary left first molar of
      rats. The JE of the right molar was used as a control. Although the whole PIE of
      undecalcified sections appeared to be attached to the implant surface, electron
      microscopically, the internal basement lamina (IBL) and hemidesmosomes were
      deficient in the coronal-middle region of the PIE. There were extensive
      extracellular deposits of HRP in the intercellular spaces between PIE cells, and
      HRP was blocked to some extent by the lamina lucida and lamina densa of the
      external basal lamina and basal cell junction. HRP was detected in the connective
      tissue under the PIE, but was not found in the connective tissue under the JE.
      Intracellularly, HRP was found in the vesicles and granules of PIE cells and JE
      cells. These were fewer in number in PIE cells than in JE cells. There were no
      differences between the findings for immediate and delayed implantation. The
      results indicate that a deficiency in the IBL permitted penetration of HRP from
      the gingival sulcus into the connective tissue under the PIE, and suggest that
      the endocytotic capacity of PIE cells is inferior to that of JE cells.

PMID- 12010155
TI  - Resonance frequency and removal torque analysis of implants with turned and
      anodized surface oxides.
AB  - The present experimental study was designed to address two issues. The first was
      to investigate whether oxide properties of titanium implants influenced bone
      tissue responses after an in vivo implantation time of six weeks. If such a
      result was found, the second aim was to investigate which oxide properties are
      involved in such bone tissue responses. Screw-shaped implants with a wide range
      of oxide properties were prepared by electrochemical oxidation methods, where the
      oxide thickness varied in the range of 200 nm to 1000 nm. The surface morphology
      was prepared in two substantially different ways, i.e. barrier and porous oxide
      film structures. The micropore structure revealed pore sizes of 8 microm in
      diameter, with a range in opening area from 1.27 microm 2 to 2.1 microm 2.
      Porosity ranged from 12.7% to 24.4%. The crystal structures of the titanium oxide
      were amorphous, anatase and a mixture of anatase and rutile type. The chemical
      compositions consisted mainly of TiO2. Surface roughness ranged from 0.96 microm
      to 1.03 microm (Sa). Each group of test samples showed its own, defined status
      with respect to these various parameters. The oxide properties of turned
      commercially pure titanium implants were used in the control group, which was
      characterized by an oxide thickness of 17.4 +/- 6.2 nm, amorphous type in
      crystallinity, TiO2 in chemical composition, and a surface roughness of 0.83
      microm (Sa). Bone tissue responses were evaluated by resonance frequency
      measurements and removal torque tests that were undertaken six weeks after
      implant insertion in rabbit tibia. Implants that had an oxide thickness of
      approximately 600, 800 and 1000 nm demonstrated significantly stronger bone
      responses in the evaluation of removal torque values than did implants that had
      an oxide thickness of approximately 17 and 200 nm (P < 0.05). However, there were
      no difference between implants with oxide thicknesses of 17 and 200 nm (P =
      0.99). It was concluded that oxide properties of titanium implants, which include
      oxide thickness, micropore configurations and crystal structures, greatly
      influence the bone tissue response in the evaluation of removal torque values.
      However, it is not fully understood whether these oxide properties influence the
      bone tissue response separately or synergistically.

PMID- 12010156
TI  - A long-term follow-up study of non-submerged ITI implants in the treatment of
      totally edentulous jaws. Part I: Ten-year life table analysis of a prospective
      multicenter study with 1286 implants.
AB  - In this prospective multicenter study, non-submerged ITI implants were followed
      in order to evaluate their long-term prognosis in fully edentulous jaws. A total
      of 1286 implants were inserted in 233 consecutive patients and, after a healing
      period of three to six months, the successfully integrated implants were restored
      with 163 overdentures and 95 fixed full-arch bridges. This prospective study not
      only calculated the 10-year cumulative survival and success rates for the 1286
      implants by life table analysis, but also evaluated the actual survival and
      success rates for 498 implants after at least five years of functional loading.
      In addition, cumulative success rates were calculated for implant subgroups
      according to implant length and location. Additional analyses were performed to
      evaluate the estimated and actual survival and success rates of the implants in
      relation to various prosthetic rehabilitation techniques. The 10-year cumulative
      survival and success rates were 95.9% and 92.7%, respectively. The actual 5-year
      survival and success rates of the first 498 implants that were inserted were
      97.7% and 95.0%, respectively. The analysis of implant subgroups showed slightly
      more favourable cumulative success rates for 12 mm long implants (93%), in
      comparison to 10 mm and 8 mm long implants (91.6% and 89.6%, respectively). The
      cumulative success rate for mandibular implants (approximately 94%) was also more
      favourable than that for maxillary implants (approximately 91%). Patients who
      were loaded with both maxillary and mandibular prostheses maintained success
      rates well above 90%; while only implants that were inserted to support maxillary
      overdentures that were retained by Dolder bars showed a success rate below 90%.

PMID- 12010157
TI  - Evaluation of implants placed with barrier membranes. A restrospective follow-up
      study up to five years.
AB  - This follow-up study evaluated clinical and radiographic parameters of dental
      implants placed in combination with guided bone regeneration with barrier
      membranes. All implants functioned well up to 60 months after insertion. Forty
      one patients, with a total of 72 augmented implants, who participated in a
      regular maintenance protocol, were investigated. Annual Periotest values (median
      value, - 3) revealed stable periimplant conditions and sustained
      osseointegration. At 6 months and annually thereafter up to five years, the
      radiographic evaluation yielded mean bone losses of 0.8, 1.25, 1.39, 1.42, 1.42
      and 1.39 mm, respectively, with a range from 0 to 3.5 mm. No implant failures or
      losses were recorded. The results demonstrated stable periimplant conditions up
      to five years after membrane-protected osseous regeneration, with no significant
      differences in the radiographic bone level in regard to region, jaw or bone
      graft. Premature membrane exposure resulted in a significantly higher crestal
      bone loss up to 24 months. The newly formed bone appeared to be able to withstand
      functional loading for up to 60 months in a predictable manner.

PMID- 12010158
TI  - Immediate loading of single-tooth ITI implants in the anterior maxilla: a
      prospective 5-year pilot study.
AB  - The aim of the present study was to evaluate the success rate of immediately
      loaded single-tooth ITI solid plasma-sprayed (TPS) implants in the maxilla. Eight
      implants were loaded immediately after placement in eight different patients, and
      were followed for five years. Temporary acrylic resin restorations, which were
      fabricated from impressions that were taken immediately after implant placement,
      were connected one week later. These temporary restorations were adjusted in
      order to avoid any direct occlusive contacts. After six months, the provisional
      crowns were replaced by definitive ceramic crowns. Regular follow-ups were
      performed during the investigation period. No implants were lost, and the mean
      marginal bone level for the eight implants increased by 0.53 mm (range - 0.83 to
      + 1.54 mm) from placement to the final examination. Only minor complications were
      noted, and overall patient satisfaction was high.

PMID- 12010159
TI  - Effect of low-power laser irradiation on bony implant sites.
AB  - This study was designed to examine the effects of low-energy laser irradiation on
      osteocytes and bone resorption at bony implant sites. Five male baboons with a
      mean age of 6.5 years were used in the study. Four holes for accommodating
      implants were drilled in each iliac crest. Sites on the left side were irradiated
      with a 100 mW low-energy laser (690 nm) for 1 min (6 Joule) immediately after
      drilling and insertion of four sandblasted and etched (Frialit-2 Synchro)
      implants. Five days later, the bone was removed en bloc and was evaluated
      histomorphometrically. The mean osteocyte count per unit area was 109.8 cells in
      the irradiated group vs. 94.8 cells in the control group. As intra-individual
      cell counts varied substantially, osteocyte viability was used for evaluation. In
      the irradiated group, viable osteocytes were found in 41.7% of the lacuna vs.
      34.4% in the non-irradiated group. This difference was statistically significant
      at P < 0.027. The total resorption area, eroded surface, was found to be 24.9% in
      the control group vs. 24.6% in the irradiated group. This difference was not
      statistically significant. This study showed that osteocyte viability was
      significantly higher in the samples that were subjected to laser irradiation
      immediately after implant site drilling and implant insertion, in comparison to
      control sites. This may have positive effects on the integration of implants. The
      bone resorption rate, in contrast, was not affected by laser irradiation.

PMID- 12010160
TI  - Thermal changes observed at implant sites during internal and external
      irrigation.
AB  - In the preparation of osseointegrated dental implant sites, the use of bone
      drilling with conventional external irrigation has been shown to be thermally non
      injurious to bovine bone, when employed as a model for dental implantology. The
      use of internal irrigation drilling systems is promoted on the basis of improved
      delivery of coolant to the bone/drill interface, which should subsequently
      improve local debridement and cooling, and therefore reduce thermal insults to
      the bone. The aim of this bovine model study was to compare the temperatures that
      were generated with external and internal irrigation systems during bone
      preparation for dental implants. A constant drill load of 1.7 kg was applied
      throughout the drilling procedures via a drilling rig. The burs that were used
      for both irrigation methods were a 2 mm twist drill for cutting the channel and a
      3.25 mm drill for trephining this channel. The principal recorded parameter was
      the change in temperature generated via the drilling procedure. The 2 mm twist
      drills produced a maximum change in temperature of only 3.0 degrees C and 3.1
      degrees C for the internal and external irrigation systems, respectively. Maximum
      changes for the 3.25 mm drills were 1.34 degrees C and 1.62 degrees C,
      respectively. Using the t-test, no statistical benefit was observed for one
      irrigant delivery system over the other. The clinical benefit of using the more
      expensive internal irrigation systems is therefore deemed unjustifiable, on the
      grounds that these systems do not appear to reduce the thermal challenge to the
      bone over and above that of simple flood irrigation.

PMID- 12010161
TI  - Bone collected during dental implant surgery: a clinical and histological study.
AB  - Bone traps vary in design, although the effect of pore size on the nature of the
      debris collected in vivo has not yet been established. The aims of this study
      were 1) to compare the clinical performance of two bone collectors during implant
      surgery, ii) to establish the mass of tissue collected by each device, and iii)
      to characterize the nature of the collected debris. Thirty-eight patients (paired
      for implant site) were categorised into three clinical groups according to the
      site and the number of implants they were to receive. Patients underwent bone
      collection with the Frios bone trap or the Osseous Coagulum Trap according to a
      randomisation sequence. The samples were fixed in formalin, frozen, freeze-dried
      and weighed. Material from each sample was embedded in paraffin wax and stained
      with haematoxylin and eosin. All sections were examined by optical microscopy and
      the proportion of bone to coagulum was established histomorphometrically. During
      surgery, the Frios bone trap blocked once and the Osseous Coagulum Trap blocked
      11 times. In all cases where blockage occurred, excess coagulum was apparent. All
      the samples that were collected by the Frios bone trap contained bone and
      coagulum, with a mean proportion of 90.6% bone. With regard to the Osseous
      Coagulum Trap, one sample contained no bone and two samples contained only trace
      amounts of bone; the remaining samples contained a mean proportion of 67.3% bone.
      Pore size affects both clinical performance and the histological composition of
      the debris collected, and this might have important implications if used as an
      augmentation material.

PMID- 12010162
TI  - Injectable calcium phosphate cement as a filler for bone defects around oral
      implants: an experimental study in goats.
AB  - The aim of this study was to evaluate the clinical applicability and biological
      behavior of a newly developed injectable calcium phosphate (Ca-P) cement as bone
      filler for gaps around oral implants. Twenty-four step-like implants, creating
      gaps of 1 and 2 mm, were inserted into the trabecular bone of the medial femoral
      condyles of six goats. Four different situations were tested: (1) implant + gaps;
      (2) implant + gaps, but covered with a polylactic acid membrane; (3) implant +
      gaps that were filled with Ca-P cement; and (4) implant + gaps that were filled
      with Ca-P cement and covered with a membrane. All implants were left in place for
      12 weeks. Histological and quantitative histomorphometrical measurements
      demonstrated that implants + gaps had generally poor bone contact at the implant
      base. Furthermore, fibrous encapsulation was observed in the gap part. In
      contrast, the presence of a membrane promoted bone ingrowth into the gap and also
      the bone contact at the implant base. Injection of Ca-P cement resulted in an
      almost complete filling of the gaps around the implant. The cement surface was
      completely covered by bone. Active resorption and remodeling of cement particles
      was observed, suggesting a pattern of slow resorption associated with full
      replacement with newly formed bone. Additional use of a membrane did not result
      in adjunctive benefits. Bone-to-implant contact at the implant base was
      comparable with the implants provided only with a membrane. In conclusion, the Ca
      P cement used here showed excellent clinical handling properties combined with a
      superior bone behavior. On the other hand, the degradation rate of the material
      was still very slow. This current characteristic can hamper the final clinical
      applicability of the material as gap filler for periimplant or periodontal
      defects.

PMID- 12010163
TI  - Effect of RGD peptide coating of titanium implants on periimplant bone formation
      in the alveolar crest. An experimental pilot study in dogs.
AB  - The aim of the present study was to analyse the effect of organic coating of
      titanium implants on periimplant bone formation and bone/implant contact. Three
      types of implants were used: (i) Ti6Al4V implants with polished surface (control
      1) (ii) Ti6Al4V implants with collagen coating (control 2) (iii) Ti6Al4V implants
      with collagen coating and covalently bound RGD peptides. All implants had square
      cross-sections with an oblique diameter of 4.6 mm and were inserted press fit
      into trephine burr holes of 4.6 mm in the mandibles of 10 beagle dogs. The
      implants of five animals each were evaluated after a healing period of 1 month
      and 3 months, during which sequential fluorochrome labelling of bone formation
      was performed. Bone formation was evaluated by morphometric measurement of the
      newly formed bone around the implant and the percentage of implant bone contact.
      After 1 month there was only little bone/implant contact, varying between 2.6 and
      6.7% in the cortical bone and 4.4 and 5.7% in the cancellous bone, with no
      significant differences between the three types of implants. After 3 months,
      implants with polished surfaces exhibited 26.5 and 31.2% contact in the cortical
      and cancellous bone, respectively, while collagen-coated implants had 19.5 and
      28.4% bone contact in these areas. Implants with RGD coating showed the highest
      values with 42.1% and 49.7%, respectively. Differences between the surface types
      as such were not significant, but the increase in bone/implant contact from 1 to
      3 months postoperatively was significant only in the group of RGD-coated implants
      (P = 0.008 and P = 0.000). The results of this pilot study thus provide only weak
      evidence that coating of titanium implants with RGD peptides in the present form
      and dosage may increase periimplant bone formation in the alveolar process. The
      results therefore require further verification in a modified experimental
      setting.

PMID- 12010164
TI  - Food selection and perceptions of chewing ability following provision of implant
      and conventional prostheses in complete denture wearers.
AB  - The loss of natural teeth compromises chewing efficiency, and edentulous patients
      often have a diet that is deficient in fibre and vitamins. Prostheses that are
      retained on implants offer the possibility of overcoming some of the limitations
      of conventional dentures in terms of chewing efficiency. The aim of this study
      was to test the hypothesis that improvement in satisfaction with oral prostheses
      would result in improved food selection in edentulous patients. This prospective
      study involved three groups, namely (i) subjects who requested and received
      implants to stabilise a complete fixed or removable prosthesis (IG, n = 26), (ii)
      edentulous subjects who requested implant prostheses, but received conventional
      dentures (CDG1, n = 22), and (iii) edentulous subjects who requested and received
      conventional dentures (CDG2, n = 35). Data were collected using validated
      questionnaires pre- and postoperatively. Prior to treatment, all subjects were
      asked whether they ate a variety of hard and soft foods, to indicate the degree
      of difficulty they experienced when chewing these foods, and to rate their
      satisfaction with various aspects of their maxillary and mandibular complete
      dentures. Following the completion of treatment, subjects completed the
      questionnaires again. Pre- and postoperative data were compared. Subjects who
      received implant prostheses reported significant improvement in chewing hard and
      soft foods. CDG2 subjects also reported improvement, but CDG1 subjects reported
      no change or even deterioration following treatment. Despite reported improvement
      in satisfaction with comfort and ability to chew food, 30-50% of IG and CDG2
      subjects still avoided eating foods such as carrot and apple. This suggests that,
      in the absence of tailored dietary advice, apparently successful prosthetic
      rehabilitation does not necessarily result in a satisfactory diet.

PMID- 12010165
TI  - Peri-implant bone tissue strains in cases of dehiscence: a finite element study.
AB  - When patients with a narrow alveolar bone ridge are treated with oral implants, a
      dehiscence can occur. The lack of bony support at the buccal or lingual side of
      the implant may present an unfavourable situation from a biomechanical point of
      view. The hypothesis as to whether the presence of dehiscence leads to an
      increased risk of marginal bone overload was tested by means of the finite
      element method. Three different situations for a cylindrical oral implant, which
      was placed in a mandible, were modelled: i) no dehiscence, ii) a dehiscence at
      the buccal side and iii) dehiscences at the buccal and lingual sides. It was
      found that the presence of buccal and/or lingual dehiscences led to a marked
      increase in marginal bone strains at the mesial and distal sides of the implant,
      thus increasing the risk of bone tissue overload at these locations. Marginal
      bone strains at the buccal and/or lingual sides, however, did not increase.

PMID- 12010166
TI  - Tooth-implant connection: some biomechanical aspects based on finite element
      analyses.
AB  - This study investigated, with the use of two- and three-dimensional finite
      element analysis, the peri-implant stress that occurred during loading of a tooth
      that was rigidly connected to a distally placed implant. A fixed bond between the
      bone and the implant was assumed, while the periodontal ligament was represented
      by means of three-dimensional nonlinear visco-elastic spring elements. Two
      different loading conditions were compared in the study: i) an axially directed
      static load of 50 kg that was applied to the tooth for 10 s, and ii) a
      transitional load of 50 kg that was applied for 5 milliseconds. Load duration
      appeared to have a greater influence than load intensity on the stress
      distribution in the bone around an implant and a rigidly connected tooth. Static
      load is, therefore, potentially more harmful for peri-implant bone than
      transitional load. The periodontal ligament seems to play a key role in the
      stress distribution between a tooth and a rigidly connected implant.

PMID- 12010167
TI  - Streptococcal toxic shock syndrome.
AB  - Perhaps more noteworthy than the emergence of Streptococcal toxic shock syndrome
      (StrepTSS) is its persistence for a period of more than 15 years in most
      geographical areas and an actual increase in incidence in some regions. Early
      diagnosis remains a problem, and aggressive surgery often cannot be avoided. The
      continuing rates of mortality and morbidity indicate the need for novel
      approaches to diagnosis and treatment.

PMID- 12010168
TI  - New developments in laboratory monitoring of HIV-1 infection.
AB  - The laboratory tests currently available to the clinician for day-to-day
      management of HIV infection are generally limited to the measurement of the viral
      load and of the CD4 cell count. More recently, analysis of drug resistance and of
      plasma drug levels have been added to the monitoring armamentarium. There are,
      however, numerous other techniques currently available to researchers that may in
      the future be incorporated into clinical routine. These include the analysis of
      human and viral genetic determinants of disease evolution, detailed analyses of
      immune recovery and reserve, pharmacogenetic determinants of treatment response,
      and toxicity. These approaches may in the future provide highly individualized
      disease management.

PMID- 12010169
TI  - Multiresistant Acinetobacter infections: a role for sulbactam combinations in
      overcoming an emerging worldwide problem.
AB  - Recent studies have highlighted the emergence of infections involving
      multiresistant Acinetobacter clinical isolates. Sulbactam offers direct
      antimicrobial activity against Acinetobacter species. Accordingly, co
      administration of sulbactam with ampicillin or cefoperazone offers the potential
      of effective empirical therapy against Acinetobacter and other bacteria such as
      Enterobacteriaceae in institutions in which they are susceptible. Many in vitro
      studies have indicated that Acinetobacter remains fully susceptible to ampicillin
      sulbactam or cefoperazone-sulbactam. Furthermore, ampicillin-sulbactam has proven
      clinically effective and well tolerated in the treatment of severe acinetobacter
      infections, including bacteremia. Therefore, ampicillin-sulbactam is a sensible
      option for the treatment of life-threatening acinetobacter infections.

PMID- 12010170
TI  - Combination of pulsed-field gel electrophoresis (PFGE) and single-enzyme
      amplified fragment length polymorphism (SAFLP) for differentiation of
      multiresistant Salmonella enterica serotype typhimurium.
AB  - OBJECTIVE: To assess the combined application of plasmid profile typing, pulsed
      field gel electrophoresis (PFGE) and PCR-based single-enzyme amplified fragment
      length polymorphism (SAFLP) for the differentiation of 18 multiresistant (MR) and
      one drug-sensitive strain of Salmonella enterica serotype typhimurium from humans
      and food animals. METHODS: Strains were phage typed and tested for resistance to
      a panel of antimicrobial agents. Strains were also tested for the ability to
      transfer resistance either directly or by mobilization to standard strains of
      Escherichia coli K12. Plasmid DNA was extracted from both drug-resistant donor
      strains and from drug-resistant exconjugants. Total genomic DNA was characterized
      by PFGE following digestion with the restriction endonuclease XbaI. The resultant
      patterns were categorized and analyzed by dendrogram analysis using the Dice
      coefficient and by data clustering using unweighted pair-group arithmetic
      averaging (UPGMA). Isolates were also characterized and categorized by SAFLP. The
      levels of discrimination achieved by each method were assessed individually and
      in combination. RESULTS: Plasmid DNA was detected in all of the 18 MR isolates
      but, not in the drug-sensitive isolate. Using PFGE, 19 different profiles were
      identified, falling into eight major categories. However, by SAFLP, only eight
      profiles were observed. Subsequent investigations have demonstrated epidemiologic
      relationships within at least one of these SAFLP profile groupings. CONCLUSIONS:
      These studies have demonstrated that PFGE and SAFLP can be used independently for
      the differentiation of MR S. Typhimurium from humans and food animals. However,
      when used in combination, SAFLP can provide a format for broad epidemiologic
      groupings. These groupings can be further subdivided by PFGE to provide detailed
      information on putative strain relationships at the genotypic level.

PMID- 12010171
TI  - Identification of Malassezia species from patient skin scales by PCR-RFLP.
AB  - OBJECTIVE: This study was aimed at the development of a DNA-based procedure
      directly applicable to pathological skin scales and at the assessment of its
      value in rapid laboratory confirmation and identification of each of the seven
      Malassezia species. These lipophilic basidiomycetous yeasts in predisposed
      individuals are involved in pityriasis versicolor, seborrheic dermatitis,
      blepharitis, folliculitis, atopic dermatitis and fungemia. Standard
      identification procedures to species level are available, but so far no system
      for direct detection and characterization of Malassezia species in clinical
      specimens is available. METHODS: Malassezia DNA was extracted from pathological
      skin scales by a modified hexadecyltrimethylammonium bromide (CTAB) method and
      amplified by single and nested polymerase chain reaction (PCR), assays using the
      general fungal ITS 1/4 and 3/4 primers for amplification of sequences from the
      Malassezia major ribosomal DNA complex. Restriction fragment length polymorphism
      (RFLP) analysis of PCR products was used in subsequent species identification.
      DNA extracted from culture-positive skin scales was also tested by PCR and the
      RFLP patterns obtained were analyzed. RESULTS: A total of 36 isolates were
      tested. Distinct pure culture and skin-scale ITS 3/4 HinfI and AluI restriction
      patterns differentially identified M. furfur, M. globosa, M. restricta, M.
      sympodialis, M. pachydermatis, M. obtusa and M. slooffiae. Malassezia DNA was
      extracted from pathological skin scales and RFLP identified solitary and multiple
      Malassezia species in the same specimen. Molecular identification was confirmed
      by cultures and biochemical tests. Concurrent detection and identification of
      Candida and Yarrowia species was also feasible from skin scales. CONCLUSION: The
      proposed method, described for the first time, could provide a sensitive and
      rapid detection and identification system for Malassezia species, which may be
      applied to epidemiological surveys and routine practice.

PMID- 12010172
TI  - Streptococcal toxic shock syndrome: a description of 14 cases from North
      Yorkshire, UK.
AB  - OBJECTIVE: To analyze the clinical and laboratory features of patients diagnosed
      with streptococcal toxic shock syndrome (TSS) in North Yorkshire from 1986 to
      1999. METHODS: Records of patients with features satisfying the published
      criteria for streptococcal TSS were reviewed from laboratory and clinical records
      made at the time and from the hospital case notes. Isolates of streptococci were
      analyzed for serotype and genes encoding for the production of streptococcal
      pyrogenic exotoxins. RESULTS: Fourteen patients satisfied the entry criteria. In
      one district, where the data were complete, the annual incidence of detected
      streptococcal TSS rose from 1.1 to 9.5 cases per million population in the 1990s.
      TSS was associated with various M serotypes of group A streptococci and various
      exotoxin genotypes. Two cases (14% of the series) were associated with severe
      group G streptococcal infection. The fatality rate was 64%, and the mode of time
      to death was 4 days. Local tissue necrosis occurred in 71% of cases, including
      necrotizing fasciitis, intrathoracic and intra-abdominal forms. Non-steroidal
      anti-inflammatory drugs (NSAIDs) had been taken around the time of onset of
      disease by 92% of the patients with TSS. CONCLUSIONS: There has been a dramatic
      increase in the number of detected cases of streptococcal TSS over the 14 years
      since the first case was recognized here. There was a wide range of invasive
      forms of infection, a high fatality rate even in fit young adults, and a rapid
      course from onset to death. There was a high association of TSS with aggressive
      streptococcal infection producing local tissue necrosis.

PMID- 12010173
TI  - Clinical microbiological case: esophago-airway fistula in an AIDS patient.

PMID- 12010174
TI  - Vero cytotoxin-producing Escherichia coli in a study of infectious intestinal
      disease in England.
AB  - An investigation of infectious intestinal disease in England included examination
      of feces for Vero cytotoxin-producing Escherichia coli (VTEC). Using DNA probe
      hybridization 27 VTEC strains were identified, 12 were from cases, and of these
      three belonged to serogroup O157. The remaining 15 strains were isolated from
      controls. The strains were confirmed biochemically as E. coli, they were
      serotyped and characterized according to their toxin production, the presence of
      sequences encoding intimin (eae) and enterohemolysin was determined and
      resistance to antimicrobial agents was determined. Six of the nine cases with non
      O157 VTEC were less than 16 years old, only two of the 15 controls were under 16.
      Infection with more than one micro-organism was also considered.

PMID- 12010175
TI  - Variable flagella expression among clonal toxin A-/B+Clostridium difficile
      strains with highly homogeneous flagellin genes.

PMID- 12010176
TI  - Clinical microbiological case: esophago-airway fistula in an AIDS patient.

PMID- 12010177
TI  - Role of trophic factors in the development, survival and repair of primary
      auditory neurons.
AB  - 1. Neurotrophic factors have been identified as crucial for the development of
      the auditory system and have also been proven to be important for continued
      survival and maintenance of auditory neural connections. 2. In addition, both in
      vitro and in vivo studies have demonstrated that these trophic molecules can
      prevent the secondary wave of auditory neuron degeneration normally seen
      following the loss of hair cells. 3. Furthermore, neurotrophic factors have been
      reported to enhance neuronal excitation and to improve the efficacy of synaptic
      transmission. 4. As such, these molecules are strong candidates to be used as
      therapeutic agents in conjunction with the cochlear implant, or even to repair
      and/or regenerate damaged or lost auditory nerve and sensory cells.

PMID- 12010178
TI  - Acute effects of L- and T-type calcium channel antagonists on cardiovascular
      reflexes in conscious rabbits.
AB  - 1. The effects of the relatively selective T-type voltage- operated calcium
      channel (VOCC) antagonist mibefradil were compared with verapamil, an L-type VOCC
      antagonist, on a range of autonomic reflexes in conscious rabbits. 2. Mean
      arterial pressure (MAP), heart rate (HR), the baroreceptor-HR reflex, postural
      adaptation reflex (90 degrees head-up tilt), Bezold-Jarisch-like reflex and the
      vasoconstrictor component of the nasopharyngeal reflex were assessed before and
      during i.v. infusion of vehicle (saline), mibefradil or verapamil. Doses of
      mibefradil that gave low (M1; 0.45 +/- 0.02 microg/mL) and high (M2; 0.93 +/-
      0.05 microg/mL) plasma concentrations, or verapamil (0.059 +/- 0.004 microg/mL; n
      = 6 each) were chosen to mimic clinically observed therapeutic levels. 3. At
      steady state infusion over 30-90 min, MAP was significantly lower in M2 (- 7
      mmHg) and verapamil (- 6 mm Hg) treatments, but only verapamil caused a
      significant tachycardia (+ 31 b.p.m.) compared with vehicle. Mibefradil (M2) and
      verapamil decreased the HR range of the baroreflex by 27 and 29%, respectively,
      but neither treatment affected the vagal or sympathetic constrictor components of
      the Bezold-Jarisch-like and nasopharyngeal reflexes, respectively. 4. In response
      to 90 degrees tilt, vehicle- and verapamil-treated rabbits responded with small
      rises in MAP of 4 +/- 2 and 8 +/- 2 mm Hg, respectively, 5 s into the upright
      posture, while M1 and M2 caused falls in MAP of 6 +/- 4 and 9 +/- 3 mm Hg,
      respectively, at 5 s. 5. Thus, both L- and T-type VOCC antagonists, at plasma
      concentrations in the clinical range, lowered MAP in the conscious rabbit, but
      only mibefradil caused postural hypotension. We conclude that T-type VOCC may
      play an important role in the venoconstrictor reflex in response to tilt in the
      rabbit.

PMID- 12010179
TI  - Quinapril treatment restores the vasodilator action of insulin in fructose
      hypertensive rats.
AB  - 1. Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve
      insulin-resistance both experimentally and clinically. We therefore investigated
      the effects of quinapril, which has high tissue specificity for ACE, regarding
      the contribution of insulin to vascular contractions, as well as insulin
      sensitivity in a dietary rat model of insulin resistance. 2. Male Sprague-Dawley
      rats were divided into three groups: (i) rats fed normal chow (normal diet
      group); (ii) rats fed fructose-rich chow containing 40% fructose and 7% lard
      (fructose diet group); and (iii) rats fed fructose-rich chow plus quinapril (10
      mg/kg per day; quinapril-treated group). 3. After 2 weeks, we evaluated systolic
      blood pressure, insulin sensitivity as assessed by steady state plasma glucose
      (SSPG) levels, response of aortic rings to phenylephrine (10-9 to 10-6 mol/L) in
      the presence or absence of insulin and the response of aortic rings to
      acetylcholine. 4. Feeding rats fructose-rich chow resulted in an elevation of
      blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment
      significantly prevented increases in both blood pressure and SSPG, with a return
      to the levels seen in the normal diet group. 5. In the absence of insulin, the
      maximal contractile response to phenylephrine did not differ between the three
      groups. However, in the presence of insulin (100 mU/mL), the contractile response
      to phenylephrine (10-6 mol/L) was reduced by 22.8 +/- 1.2% in the normal diet
      group, although no insulin effects were observed in the fructose diet group (P <
      0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine
      induced contractions. 6. In addition, the reduction in relaxation induced by
      acetylcholine in the fructose diet group was significantly reversed by quinapril
      treatment. 7. It is concluded that the fructose diet impairs the vasodilator
      effects of insulin as well as acetylcholine-induced relaxation in rat thoracic
      aortas. Quinapril prevented deterioration in the responses of the aortic rings,
      suggesting that ACE inhibitors may be useful for treating vascular insulin
      resistance.

PMID- 12010180
TI  - Beneficial effect of T-1095, a selective inhibitor of renal Na+-glucose
      cotransporters, on metabolic index and insulin secretion in spontaneously
      diabetic GK rats.
AB  - 1. To investigate the pharmacological effects of T-1095, this novel derivative of
      phlorizin was administered to GK rats for 8 weeks. T-1095 treatment significantly
      lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not
      significantly affect bodyweight. 2. T-1095 treatment did not affect 3.3 mmol/L
      glucose-induced insulin secretion in the isolated perfused pancreas of GK rats.
      3. The peak insulin release in T-1095-treated GK rats was significantly higher
      during the first phase than in untreated GK rats (3-4 min after beginning 16.7
      mmol/L glucose perfusion). The total amount of insulin secreted during the first
      phase in T-1095-treated GK rats was significantly higher than in untreated GK
      rats (35.3 +/- 1.4 vs. 27.3 +/- 2.5 ng in T-1095-treated compared with untreated
      rats, respectively). 4. During the second phase, insulin release in T-1095
      treated GK rats was somewhat higher than in untreated GK rats (7-30 min after
      beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted
      during the second phase in T-1095-treated GK rats was significantly higher than
      in untreated GK rats (88.2 +/- 6.1 vs. 68.1 +/- 5.7 ng, respectively). 5. The
      total amount of insulin secreted during perfusion in T-1095-treated GK rats was
      significantly higher than in untreated GK rats (123.5 +/- 7.3 vs. 95.4 +/- 7.7
      ng, respectively). 6. These data show that the metabolic indices, plasma glucose
      and HbA1c levels and insulin secretion are significantly improved by T-1095
      treatment in GK rats, which are spontaneously diabetic rats, suggesting its
      usefulness as a novel oral therapeutic antidiabetic agent.

PMID- 12010181
TI  - Effects of caffeine on the uncoupling protein family in obese yellow KK mice.
AB  - 1. The hypothesis that caffeine upregulates uncoupling protein (UCP)-1, UCP-2 and
      UCP-3 expression, which contribute to thermogenesis, was investigated in obese
      mice. 2. The mRNA levels of UCP-1, -2 and -3 in brown adipose tissue (BAT), UCP-2
      in white adipose tissue (WAT), and UCP-2 and -3 in skeletal muscle were measured
      using real-time quantitative reverse transcription-polymerase chain reaction
      analysis in obese yellow KK mice 4 h after the subcutaneous administration of
      either 60 mg/kg caffeine or physiological saline. Plasma free fatty acids,
      adrenaline, noradrenaline and dopamine levels were also measured. 3. In caffeine
      injected obese mice, UCP-1 mRNA levels were significantly increased by 1.5-fold
      in BAT, UCP-2 mRNA levels were increased by 1.8- and 2.5-fold in BAT and skeletal
      muscles, respectively, and UCP-3 mRNA levels were increased 1.7- and 3.4-fold in
      BAT and skeletal muscles, respectively, compared with control mice injected with
      physiological saline. There was no difference in UCP-2 mRNA levels in WAT between
      the two groups. 4. Plasma free fatty acids and adrenaline levels were
      significantly elevated in mice treated with caffeine compared with those injected
      with physiological saline. 5. It was concluded that caffeine upregulates the
      expression of UCP-1, UCP-2 and UCP-3 in BAT and UCP-2 and UCP-3 in skeletal
      muscles, which may contribute to thermogenesis in obese mice.

PMID- 12010182
TI  - Effects of molybdenum, silicon and nickel on alpha1-adrenoceptor-induced
      constriction of rat isolated aorta.
AB  - 1. To determine the effects of trace elements on alpha1-adrenoceptor-mediated
      vasoconstriction, we studied the effects of molybdenum (Mo), silicon (Si) and
      nickel (Ni) on vasoconstrictor response to an alpha1-adrenoceptor agonist in rat
      aorta. 2. Cumulative concentration-contraction curves were obtained for
      phenylephrine (1 nmol/L-10 micromol/L) in the absence and presence of Mo, Si and
      Ni (0.3, 1 and 3 micromol/L) in rat aorta rings. Increasing the concentration of
      Mo and Si from 0.3 to 3 micromol/L shifted the cumulative concentration
      contraction curve to the right, but did not reduce the maximal contractile
      response to phenylephrine. In contrast, Ni at 1 and 3 micromol/L shifted the
      cumulative concentration-contraction curve to the right and, at 3 micromol/L,
      reduced the maximum contractile response to phenylephrine. 3. We conclude that
      micromolar concentrations of Mo, Si and Ni affected alpha1-adrenoceptor-induced
      vasoconstriction and that Ni significantly inhibited the maximal contractile
      response to phenylephrine in rat isolated aorta.

PMID- 12010183
TI  - Weight reduction decreases soluble cellular adhesion molecules in obese women.
AB  - 1. Obesity is known to increase the risk for atherosclerotic diseases. Serum
      levels of cellular adhesion molecules are reported to be indices of
      atherosclerosis. The aim of the present study was to assess the effect of weight
      reduction on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E
      selectin (sE-selectin). 2. Eighteen non-diabetic normotensive obese women
      participated in a 3 month lifestyle-modification programme (intervention group).
      The programme consisted of lectures on diet, exercise sessions and behavioural
      modification by weight charting. Fourteen women who did not enter the programme
      served as controls. Body fat mass (FM) was measured by dual-energy X-ray
      absorptiometry. Soluble ICAM-1 and sE-selectin were measured by ELISA. 3. After 3
      months, sICAM-1 and sE-selectin, as well as body FM, decreased in the
      intervention group (P < 0.001), while no changes were observed in the control
      group. The baseline sE-selectin was positively correlated with total body FM,
      trunk FM and percentage body fat (r = 0.50-0.57; P < 0.01), but not with leg FM.
      The change in sE-selectin was also correlated with changes in total body FM and
      trunk FM (both r = 0.46; P < 0.01). Baseline sICAM-1 was not significantly
      correlated with these variables. The associations between changes in sICAM-1 and
      changes in total body FM or trunk FM were of borderline significance (both r =
      0.34; P = 0.06). Linear regression analysis indicated that the change in sE
      selectin was explained by the change in trunk FM (R2 = 0.18; P < 0.01). 4.
      Soluble ICAM-1 and sE-selectin were positively correlated with obesity,
      especially with central obesity. Weight reduction resulted in decreases in
      soluble adhesion molecules, which may suggest a downregulation of endothelial
      activation.

PMID- 12010184
TI  - Endothelial function in mesenteric resistance arteries from the genetically
      hypertensive rat.
AB  - 1. Endothelial function in mesenteric resistance arteries (MRA) from male 12-week
      old New Zealand genetically hypertensive (GH) rats and their normotensive control
      strain (N) was compared in vessels mounted on a wire myograph and by the
      production of intracellular cGMP. In parallel experiments, MRA from the
      spontaneously hypertensive (SHR) rat strain, in which there is an endothelial
      defect, and from GH rats, in which an endothelial defect was induced by chronic
      nitric oxide synthase (NOS) inhibition with Nomega-nitro-L-arginine methyl ester
      (L-NAME), were studied. 2. Contractile responses to potassium (124 mmol/L)
      depolarization and to NA (10(-8) to 10(-4) mol/L) were similar in GH and N rats;
      however, in SHR, enhanced contractile responses were found (P < 0.05). The
      endothelium-dependent relaxation induced by acetylcholine (ACh; 10(-9) to 10(-4)
      mol/L) and endothelium- independent relaxation induced by sodium nitroprusside
      (SNP; 10(-9) to 10(-4) mol/L) were identical in preparations from GH and N. A
      significantly attenuated (P < 0.01) vasodilator response to ACh was observed in
      preparations from SHR. 3. Levels of intracellular cGMP were similar in untreated
      small mesenteric arterial trees from GH, N and SHR rats. Acetylcholine (10-5
      mol/L) significantly (P < 0.001) increased the cGMP content in both GH and N
      rats. A non-significant increase occurred in cGMP content in preparations from
      SHR. 4. In GH rats given L-NAME (10 mg/kg per day for up to 5 weeks), an
      attenuated (P < 0.01) endothelium-dependent relaxation to ACh and an enhanced (P
      < 0.01) endothelium- independent relaxation to SNP were observed. Lower basal
      cGMP levels were found in preparations from L-NAME-treated GH rats and ACh (10-5
      mol/L) failed to significantly elevate the cGMP content in these preparations. 5.
      These experiments failed to show evidence of reduced endothelial function in GH
      rats, although an endothelial defect in SHR rats and after NOS inhibition in GH
      rats could be demonstrated.

PMID- 12010185
TI  - Age-related changes in dopamine D2 receptors in rat heart and coronary vessels.
AB  - 1. The distribution of dopamine D2 receptors in rat heart and coronary vessels
      and the possible age-related changes in D2 receptor density were studied. The
      pharmacological characteristics and the anatomical location of dopamine D2-like
      receptor sites in rat heart and coronary vessels were investigated using combined
      binding techniques and light microscopy autoradiography. 2. Samples of heart and
      coronary vessels were harvested from young and old rats. On frozen slices,
      dopaminergic D2 receptors were labelled by means of a selective D2 ligand, namely
      [3H]-spiroperidol (spiperone). Inhibition studies were performed using unlabelled
      agonists and/or labelled and unlabelled antagonists to define pharmacological
      specificity of the binding. Physiological experiments were performed to
      demonstrate the selective antagonism between D2 receptors and many dopaminergic
      drugs. 3. [3H]-Spiroperidol was bound to sections of rat heart and coronary
      artery (in a manner consistent with the labelling of dopamine D2-like receptors)
      with an equilibrium dissociation constant of approximately 2.4 +/- 0.7 nmol/L and
      a maximum capacity of binding sites of 65.8 +/- 4.5 fmol/mg protein. Experiments
      performed on sections of coronary veins did not allow the evaluation of specific
      binding. Autoradiography, observed with light microscopy, showed the development
      of specific silver grains within the whole wall of rat heart and coronary artery.
      The greater sensitivity to displacement by amisulpride, bromocriptine,
      domperidone, haloperidol, raclopride and L-sulpiride than to displacement by N
      propyl-norapomorphine, quinpirole and clozapine suggests that the binding sites
      observed in these experiments are likely to belong to the dopamine D2 receptor
      subtype. 4. Comparing results in young and old rats, we observed numerous
      significant age-related changes, including a decrease in D2 receptors localized
      in rat heart and coronary artery wall. These D2 receptors show a specific
      location, in close relationship with dopaminergic nerve fibres. They decrease
      with age and their role remains unknown.

PMID- 12010186
TI  - Decrease in catechol-O-methyltransferase activity in the liver of streptozotocin
      induced diabetic rats.
AB  - 1. The present study compared the activity of catechol- O-methyltransferase
      (COMT) in the liver and plasma of streptozotocin (STZ)-induced diabetic rats with
      that in normal rats. The activity of COMT was estimated by the metabolism of
      noradrenaline to metanephrine (MN), both measured by high-performance liquid
      chromatography with electrochemical detection. 2. Formation of MN was decreased
      in the liver of STZ- diabetic rats compared with normal rats. The amount of MN
      was also decreased in plasma obtained from STZ-diabetic rats. A Michaelis-Menten
      plot showed a reduction in the maximum velocity and an increase in the Km for
      COMT in liver samples from STZ-diabetic rats. 3. The role of hyperglycaemia in
      the lowering of COMT activity was then investigated using phlorizin or insulin at
      doses sufficient to normalize plasma glucose from STZ-diabetic rats. Both insulin
      and phlorizin treatment of STZ-diabetic rats for 4 days restored the activity of
      COMT to that seen in normal rats. Thus, correction of hyperglycaemia in STZ
      diabetic rats can reverse the decrease in COMT activity. The activity of COMT is
      lower in STZ-diabetic rats than in normal rats mainly due to the higher plasma
      glucose.

PMID- 12010187
TI  - Effect of KAD-1229, a novel hypoglycaemic agent, on plasma glucose levels after
      meal load in type 2 diabetic rats.
AB  - 1. The effects of KAD-1229 (a novel non-sulphonylurea agent), voglibose (an alpha
      glucosidase inhibitor) and nateglinide (a non-sulphonylurea antihyperglycaemic
      agent) on hyperglycaemia induced by a meal load were assessed in diabetic rats.
      2. KAD-1229 suppressed the increase in plasma glucose levels seen after a meal
      load and the area under the curve for plasma glucose levels (AUCglucose) up to 5
      h after the meal load. 3. Voglibose also suppressed the increase in plasma
      glucose levels; however, a significant decrease in AUCglucose following voglibose
      was not observed. 4. Nateglinide suppressed the increase in plasma glucose levels
      at 30 min and 1 h after the meal load; however, plasma glucose levels was above
      control thereafter and the AUCglucose was not decreased. 5. The results indicate
      that KAD-1229 has an antihyperglycaemic effect and KAD-1229 is suggested to be a
      suitable agent for controlling post-prandial hyperglycaemia.

PMID- 12010188
TI  - Effects of endomorphin-1 and -2 on mu-opioid receptors in myenteric neurons and
      in the peristaltic reflex in rat small intestine.
AB  - 1. The aim of the present investigations was to characterize the effect of
      endomorphins on the function of rat small intestine smooth muscle and on the
      electrically induced ascending and descending reflex pathway of rat small
      intestine in vitro. 2. Endomorphin-1 and -2 left the basal tonus and the
      pharmacologically stimulated smooth muscle unchanged. In contrast, electrically
      induced twitch contractions were significantly reduced by endomorphin-1 and -2
      and this reduction was reversed by the mu-opioid receptor antagonist Cys-Tyr-Orn
      Pen-amide (CTOP), suggesting a specific mu-opioid receptor-mediated effect on
      neural tissue. 3. In the reflex model, endomorphin-1 caused a significant
      inhibition (IC50 2.3 x 10(-8) mol/L) of the ascending contraction (10(-8) mol/L: 
      28.3 +/- 5.8%; 10(-7) mol/L: -94.7 +/- 0.2.8%; both P < 0.05; n = 7). Descending
      relaxation increased at a concentration of 10(-8) mol/L endomorphin-1 (+61.6 +/-
      24.5%; 10(-7) mol/L: +237.0 +/- 65.4%; both P < 0.05; n = 6). 4. Endomorphin-1
      caused a further significant increase in the latency of the ascending contraction
      (10(-8) mol/L: +44.7 +/- 20.5%; 10(-7) mol/L: +93.5 +/- 16.1%; both P < 0.05; n =
      7), whereas the latency of the descending relaxation was unaltered (n = 7).
      Similar results were observed for endomorphin-2. 5. All effects could be reversed
      by a wash-out afterwards and were blocked by pre-incubation with CTOP (10-6
      mol/L). 6. Reverse transcription-polymerase chain reaction demonstrated mRNA
      expression of mu-opioid receptors in the rat ileum longitudinal muscle/myenteric
      plexus preparation, as well as in the oesophagus and stomach. 7. Endomorphin-1
      and -2 reduce the cholinergic-induced contractile response of the rat ileal
      smooth muscle preparation via a presynaptic mechanism. 8. By a specific and
      reversible interaction with mu-opioid receptors, the ascending excitatory and
      descending inhibitory reflex responses were attenuated or facilitated,
      respectively. 9. In conclusion, the endomorphins may be the physiological
      endogenous mu-opioid receptor agonists in the rat small intestine.

PMID- 12010189
TI  - Chronic hypoxia preconditioning increases survival in rats suffering from
      heatstroke.
AB  - 1. In the present study, we assessed the protective effects of chronic hypoxia
      preconditioning against heatstroke-induced injury in urethane-anaesthetized rats.
      Heatstroke was induced by exposing the animals to an ambient temperature of 42
      degrees C. The time at which both the mean arterial pressure (MAP) and local
      cerebral blood flow (CBF) in the striatum began to decrease from peak levels was
      taken as the onset of heatstroke. Control rats were exposed to a temperature of
      24 degrees C. 2. Mean arterial pressure, CBF, blood pH, PaO2, PaCO2 and survival
      time (the interval between onset of heatstroke and cardiac arrest) after heat
      stress were all lower than in control rats (in which 'survival time' was defined
      as > 360 min). However, blood lactate concentrations were greater in rats exposed
      to heat. Rats placed at high altitude (HA), when exposed to the same heat stress
      (42 degrees C) survived much longer (113 +/- 26 min; n = 8) than rats maintained
      at sea level (SL; 20 +/- 2 min; n = 8). 3. After the onset of heatstroke, blood
      pH and lactate concentrations were found to be significantly higher and lower,
      respectively, in HA rats than in SL rats. 4. Western blot assay revealed that
      chronic hypoxia preconditioning induced heat shock protein (HSP) 72 expression in
      both the kidneys and lungs. 5. Thus, it appears that the observed benefit of
      chronic hypoxia preconditioning is related to attenuation of tissue acidification
      and elevations of HSP72 expression in both kidneys and lungs during heatstroke.

PMID- 12010190
TI  - Highly protective effects of chronic oral administration of nicorandil on the
      heart of ageing rats.
AB  - 1. We have tested the effects of 2 month oral treatment with the KATP opener,
      nitric oxide (NO) donor and anti-oxidant molecule nicorandil (0.1 mg/kg per day)
      on major physiological parameters and heart function of 4-, 12- and 24-month-old
      rats. 2. Several methods were used: (i) measurement of blood pressure using a non
      invasive tail-cuff method; (ii) perfusion of isolated heart; (iii) lactate
      dehydrogenase (LDH) dosage; and (iv) measurement of monophasic action potential
      of rat isolated hearts. 3. Blood pressure and ventricular action potential
      duration regularly increase with age in control animals, whereas nicorandil
      restores these parameters in aged animals to levels present in young adult
      animals. Moreover, following ischaemia, nicorandil treatment improved isolated
      heart survival rate (100 vs. 50% for nicorandil-treated rats and controls,
      respectively), heart work and left ventricular developed pressure, whereas it
      decreased cardiac cell damage (LDH release) and perfusion pressure. 4. This
      condition of chronic oral nicorandil treatment presents a strong potential in the
      improvement of cardiac function in normal and pathological ageing.

PMID- 12010191
TI  - Effects of glycine on glomerular filtration rate and segmental tubular handling
      of sodium in conscious rats.
AB  - 1. Infusion of the amino acid glycine leads to an increase in effective renal
      plasma flow (ERPF) and glomerular filtration rate (GFR) by a mechanism that
      possibly involves stimulation of nitric oxide (NO). Because NO also increases
      proximal tubular fluid output (Vprox) by inhibition of proximal tubular Na+
      reabsorption and modulation of the tubuloglomerular feedback system, we
      hypothesized that glycine would increase Vprox as measured by lithium clearance
      (CLi). 2. In the first series of experiments, the effect of glycine infusion (4
      mg/min) was examined in conscious, unstressed, chronically catheterized rats. In
      an additional series of experiments, the effect of glycine was examined under
      similar conditions in rats pretreated with a NO synthase (NOS) inhibitor (NG
      nitro-L-arginine methyl ester (L-NAME), 2.5 microg/min). 3. Glycine significantly
      increased ERPF (from 3268 to 4018 microL/min per 100 g bodyweight (BW)), GFR
      (from 874 to 1009 microL/min per 100 g BW), CLi (from 275 to 461 microL/min per
      100 g BW) and Na+ clearance (CNa; from 2.9 to 14.0 microL/min per 100 g BW).
      Fractional excretion of lithium (FELi; from 32 to 46%) and CNa/CLi (from 0.99 to
      2.99%) also rose, indicating inhibition of proximal and distal nephron Na+
      reabsorption, respectively. In the rats pretreated with L-NAME, similar
      haemodynamic and tubular responses to glycine infusion were seen, suggesting that
      the effects were not mediated by NO. 4. We conclude, that glycine increases ERPF
      and GFR and it also inhibits proximal and distal nephron Na+ reabsorption leading
      to an increase in CLi and CNa. There was no indication that any of these effects
      were mediated by NO.

PMID- 12010192
TI  - Effects of birth on baroreceptor-mediated changes in heart rate variability in
      lambs and fetal sheep.
AB  - 1. In adult unanaesthetized sheep, there is a V-shaped relationship between mean
      arterial pressure (MAP) and heart rate variability (HRV), measured in both time
      and frequency domains. In contrast, in fetal sheep, there is only a positive
      direct relationship between MAP and HRV, which is determined by the cardiac
      vagus. We postulated that by the time lambs were 8-10 days old, the 'adult like'
      V-shaped relationship between MAP and HRV would be present and it may appear at
      or after birth. To test these hypotheses, experiments were performed in six
      chronically catheterized fetal sheep (aged 132-138 days gestation), 10 newborn
      sheep (within 10 h of birth) and 10 lambs (aged 8-10 days). The relationships
      between MAP and HRV (in both time and frequency domains) were studied before and
      during beta-adrenoreceptor blockade with propranolol and before and during
      cardiac vagal blockade with atropine. 2. In 8-10-day-old lambs, V-shaped
      relationships between MAP and HRV (measured in both time and frequency domain)
      were obtained. The negative limb of this V-shaped relationship between MAP and
      HRV was present after cardiac vagal blockade. The positive slope of the V was
      present after beta-adrenoreceptor blockade. 3. In 4-h-old newborn sheep, there
      was no relationship between MAP and HRV (measured in the time domain), but
      between 7 and 10 h of age a negative relationship was found during treatment with
      atropine and a positive relationship was found during beta-adrenoreceptor
      blockade, when HRV was measured in both time and frequency domains. 4. As
      described previously, there was only a positive relationship between MAP and HRV
      in fetal sheep, which was abolished by atropine but not affected by beta
      adrenoreceptor blockade. 5. Thus, until relatively late in fetal life,
      baroreceptor- modulated changes in efferent cardiac sympathetic tone, determined
      by measuring the effects of autonomic blockade on HRV, could not be elicited,
      although reflex vagal pathways were active. By 7-10 h after birth, baroreceptor
      modulated changes in efferent cardiac sympathetic tone were present. It was
      possible using measurements of HRV made in the time domain to show that these
      baroreceptor-modulated cardiac sympathetic effects became stronger over the first
      10 days of life (P < 0.01). These studies are the first to show that the
      influence of baroreceptor-mediated changes in cardiac sympathetic tone on HRV
      increases in early life. This is probably because maturation of sympathetic
      innervation of the fetal sheep heart is occurring at this age.

PMID- 12010193
TI  - Antinociceptive action of captopril and transcutaneous electric nerve stimulation
      in Mus musculus mice.
AB  - 1. In the present study, the antinociceptive action of captopril was
      investigated, as well as its association with transcutaneous electric nerve
      stimulation (TENS), in mice under nociceptive stimulation. 2. The modulation of
      abdominal contortions (writhes) produced by acetic acid was observed in order to
      evaluate captopril pain stimuli blockade. 3. The administration of captopril
      produced a significant reduction of nociception, which was further reduced when
      captopril was associated with TENS. 4. Apparently this increase in the inhibition
      of nociception was produced by an indirect mechanism, involving opioid liberation
      by TENS and an enzymatic inhibition induced by captopril and this may lead to
      clinical applications of captopril and TENS association in pain relief.

PMID- 12010194
TI  - Role of angiotensin II receptors in the regulation of vasomotor neurons in the
      ventrolateral medulla.
AB  - 1. There is a high density of angiotensin type 1 (AT1) receptors in various brain
      regions involved in cardiovascular regulation. The present review will focus on
      the role of AT1 receptors in regulating the activity of sympathetic premotor
      neurons in the rostral part of the ventrolateral medulla (VLM), which are known
      to play a pivotal role in the tonic and phasic regulation of sympathetic
      vasomotor activity and arterial pressure. 2. Microinjection of angiotensin (Ang)
      II into the rostral VLM (RVLM) results in an increase in arterial pressure and
      sympathetic vasomotor activity. These effects are blocked by prior application of
      losartan, a selective AT1 receptor antagonist, indicating that they are mediated
      by AT1 receptors. However, microinjection of AngII into the RVLM has no
      detectable effect on respiratory activity, indicating that AT1 receptors are
      selectively or even exclusively associated with vasomotor neurons in this region.
      3. Under normal conditions in anaesthetized animals, AT1 receptors do not appear
      to contribute significantly to the generation of resting tonic activity in RVLM
      sympathoexcitatory neurons. However, recent studies suggest that they contribute
      significantly to the tonic activity of these neurons under certain conditions,
      such as salt deprivation or heart failure, or in spontaneously hypertensive or
      genetically modified rats in which the endogenous levels of AngII are increased
      or in which AT1 receptors are upregulated. 4. Recent evidence also indicates that
      AT1 receptors play an important role in mediating phasic excitatory inputs to
      RVLM sympathoexcitatory neurons in response to activation of some neurons within
      the hypothalamic paraventricular nucleus. The physiological conditions that lead
      to activation of these AT1 receptor-mediated inputs are unknown. Further studies
      are also required to determine the cellular mechanisms of action of AngII in the
      RVLM and its interactions with other neurotransmitters in that region.

PMID- 12010195
TI  - Angiotensin peptides as neurotransmitters/neuromodulators in the dorsomedial
      medulla.
AB  - 1. The present review provides an update on evidence of the neurotransmitter
      pathways and location of receptors within the nucleus tractus solitarii (NTS)
      mediating the baroreflex and other haemodynamic actions of angiotensin (Ang) II.
      2. A series of studies suggests a significant role for substance P in the acute
      cardiovascular and carotid sinus chemoreceptor facilitatory actions of AngII in
      the NTS. The use of antisense oligonucleotides to AT1 receptors indicates both
      pre- and post-synaptic AngII receptors are likely to be involved in these
      actions. 3. With respect to baroreceptor reflex actions, it is clear that
      endogenous AngII impairs the gain for operation of the baroreceptor reflex,
      because AT1 receptor antagonists facilitate reflex function. This effect is
      either independent of substance P or involves inhibition of release. Moreover,
      initial data obtained using antisense oligonucleotides to AT1 receptors suggest
      that, in the NTS, the effect of endogenous AngII on the baroreceptor reflex is
      mainly due to presynaptic actions on vagal or carotid sinus afferent fibres. In
      contrast, the level of endogenous AngII within the NTS appears to have variable
      effects on activation of cardiopulmonary vagal afferent fibres by
      phenylbiguanide. These results indicate a divergence of effects of AngII on
      reflexes evoked by these two different types of sensory input. 4. Use of
      transgenic rats with alterations in brain angiotensin peptides allowed us to
      assess the effect of long-term alterations in brain Ang peptides on reflex
      function. We studied (mRen2)27 transgenic rats (TGR(mRen2)) with high brain
      medulla AngII levels and transgenic rats with angiotensinogen (Aogen) antisense
      linked to glial fibrillary acidic protein promoter (TGR(ASrAogen)) with greatly
      reduced brain Aogen. The reflex evoked by activation of cardiac vagal
      chemosensitive afferent fibres was enhanced in TGR(ASrAogen), whereas the
      baroreceptor reflex control of heart rate was attenuated in TGR(mRen2), further
      confirming a divergence of effects of AngII on these two sensory modalities. 5.
      The overall results are consistent with a sustained inhibitory effect of AngII on
      the baroreceptor reflexes, with dose-dependent or activation-dependent effects on
      cardiac vagal afferent fibre activation. Moreover, alterations in substance P
      pathways may contribute to the actions of AngII on reflex function.

PMID- 12010196
TI  - Angiotensin AT1 receptor signalling pathways in neurons.
AB  - 1. The aim of the present article is to review the intracellular signal
      transduction pathways that are influenced by the peptide angiotensin (Ang) II,
      acting via its type 1 (AT1) receptor, in neurons. 2. The AT1 receptors couple to
      a wide variety of signalling pathways in peripheral tissues, such as kidney,
      heart and vascular smooth muscle. A similar diversity of signalling mechanisms
      exists for AT1 receptors in neurons. 3. We outline the known neuronal AT1
      receptor signalling pathways as they relate to function. Pathways that couple
      activation of AT1 receptors to short-term changes in neuronal membrane ionic
      currents and firing rate will be reviewed. These are different from the pathways
      that elicit longer-term changes in enzyme activity and gene expression and,
      ultimately, increases in noradrenaline synthesis. 4. Novel AT1 receptor
      signalling pathways discovered through gene expression profiling and their
      potential functional significance have been discussed.

PMID- 12010197
TI  - Glutamate circuits in selected medullo-spinal areas regulating cardiovascular
      function.
AB  - 1. The importance of the medullo-spinal neuronal pools in the regulation of
      cardiovascular function has been known for a long time. However, important groups
      of these neurons, interconnections between them and the neurotransmitters
      released at their projections have been identified with certainty only during the
      past two decades. 2. Some of the medullo-spinal neuronal pools mediating
      cardiovascular function include the nucleus tractus solitarius, caudal
      ventrolateral medullary depressor area, rostral ventrolateral medullary pressor
      area, nucleus ambiguus and intermediolateral cell column of the thoracolumbar
      spinal cord. Interactions between these selected neuronal groups and
      neurotransmitters in the pathways connecting them are discussed in the present
      short review.

PMID- 12010198
TI  - Glutamatergic neural transmission in the nucleus tractus solitarius: N-methyl-D
      aspartate receptors.
AB  - 1. The nucleus tractus solitarius (NTS) is the first central site where the
      reflex control of autonomic, including baroreceptor, reflex function is
      coordinated. Autonomic signals are transmitted from the first-order visceral
      afferent fibres to second-order NTS neurons by L-glutamate. It is well
      established that activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      proprionic acid (AMPA) receptors, which mediate the fast component of L-glutamate
      signalling, is required for generating changes in membrane potentials of the
      second-order NTS neurons. The contribution of the slower-developing, longer
      lasting N-methyl-D-aspartate (NMDA) receptor-mediated component of glutamate
      signalling to synaptic transmission at these synapses is less well understood. 2.
      The aim of this work is to highlight evidence that functional NMDA receptors
      exist on second-order NTS neurons in autonomic, including baroreceptor, afferent
      pathways by determining whether NMDA receptors can be activated by: (i) exogenous
      application of NMDA; and (ii) endogenous release of L-glutamate from autonomic
      afferent fibres. Studies were performed on second-order neurons in transverse and
      horizontal brainstem slices containing the intermediate NTS and the tractus
      solitarius. Second-order NTS neurons were identified by electrophysiological
      criteria or by attached fluorescent-labelled aortic depressor nerve (ADN)
      boutons. 3. N-Methyl-D-aspartate (50 nmol(-2) micromol) dose-dependently evoked
      excitatory post-synaptic currents in second-order NTS neurons (P = 0.004; n = 4).
      The NMDA receptor-mediated currents were also synaptically evoked by low
      frequency stimulation of the autonomic afferent fibres in the tractus solitarius.
      The NMDA receptor-mediated currents were blocked by the NMDA receptor antagonist
      AP5 (n = 7; P = 0.027). 4. The findings suggest that functional NMDA receptors
      exist on second-order NTS neurons. While the NMDA receptor- mediated currents may
      not be required for signal transmission when the second-order neurons are at
      resting membrane potential, their activation may help to modulate autonomic
      signal transmission in the NTS under conditions in which the membrane is
      depolarized by high frequency or convergent inputs.

PMID- 12010199
TI  - Role of excitatory amino acid inputs to the rostral ventrolateral medulla in
      cardiovascular regulation.
AB  - 1. Excitatory amino acid (EAA)-mediated neural transmission in the rostral
      ventrolateral medulla (RVLM) is important for many cardiovascular reflexes,
      although the receptor subtypes involved vary depending on the specific response.
      2. Although injection of the EAA ionotropic receptor antagonist kynurenic acid
      into the RVLM has no effect on baseline arterial pressure, this lack of effect
      appears to result from EAA inputs to RVLM exciting both excitatory and inhibitory
      mechanisms within the RVLM. 3. The balance between EAA-mediated excitation and
      inhibition of RVLM neurons may be shifted to excitation in experimental models of
      hypertension. 4. The excitatory influence that EAA inputs to the RVLM have on
      vasomotor neurons in the RVLM may involve a sarthran-sensitive intermediary in
      the RVLM.

PMID- 12010200
TI  - GABA in the control of sympathetic preganglionic neurons.
AB  - 1. Amino acid neurotransmitters are critical for controlling the activity of most
      central neurons, including sympathetic preganglionic neurons (SPN), the spinal
      cord neurons involved in controlling blood pressure and other autonomic
      functions. 2. In studies reviewed here, SPN were identified either by retrograde
      tracing from a peripheral target (superior cervical ganglion or adrenal medulla)
      or by detection of immunoreactivity for choline acetyltransferase (ChAT), the
      acetylcholine-synthesizing enzyme that is a marker for all SPN, in intact or
      completely transected rat spinal cord. 3. Postembedding immunogold labelling on
      ultrathin sections was then used to detect GABA and sometimes glutamate in nerve
      terminals on SPN or near them in the neuropil of the lateral horn. 4. In some
      cases, the terminals were prelabelled to show an anterograde tracer or
      immunoreactivity for ChAT or neuropeptide Y. 5. This anatomical work has provided
      information that is helpful in understanding how SPN are influenced by their
      GABAergic innervation. 6. Immunogold studies showed that the proportion of input
      provided by GABAergic terminals varies between different groups of SPN. For some
      groups, this input may be preferentially targeted to cell bodies. 7. Anterograde
      tracing demonstrated that supraspinal as well as intraspinal GABAergic neurons
      innervate SPN and investigations on completely transected cord suggested that
      supraspinal neurons may provide a surprisingly large proportion of the GABAergic
      terminals that contact SPN. 8. The double-labelling studies in which other amino
      acids, ChAT or neuropeptide Y were localized along with GABA indicate that
      GABAergic terminals contain other neurochemicals that could modulate the actions
      of GABA, depending on the complement of receptors that are present pre- and post
      synaptically. 9. Taken together, these data indicate that GABAergic transmission
      to SPN may be much more complicated than suggested by the currently available
      electrophysiological studies.

PMID- 12010201
TI  - The baroreflex and beyond: control of sympathetic vasomotor tone by GABAergic
      neurons in the ventrolateral medulla.
AB  - 1. Barosensitive, bulbospinal neurons in the rostral ventrolateral medulla
      (RVLM), which provide the major tonic excitatory drive to sympathetic vasomotor
      neurons, are prominently inhibited by GABA. 2. A major source of the GABAergic
      inhibition to presympathetic RVLM neurons arises from an area immediately caudal
      to the RVLM, known as the caudal ventrolateral medulla (CVLM). 3. Arterial
      baroreceptor afferents projecting to the nucleus tractus solitarius (NTS) provide
      a major tonic excitatory input to GABAergic CVLM neurons. These CVLM cells are a
      critical component for baroreflex-mediated changes in presympathetic RVLM
      neuronal activity, sympathetic nerve activity (SNA) and arterial pressure (AP).
      4. Some GABAergic CVLM neurons are tonically activated by inputs independent of
      arterial baroreceptors or the NTS, providing a GABAergic-mediated inhibition of
      the presympathetic RVLM neurons that is autonomous of baroreceptor inputs. 5.
      GABAergic CVLM neurons appear to play two distinct, yet important, roles in the
      regulation of sympathetic vasomotor tone and AP. They dampen immediate changes in
      AP via the baroreflex and tonically inhibit the activity of the presympathetic
      RVLM neurons by baroreceptor-independent mechanisms. This baroreceptor
      independent, GABAergic inhibition of presympathetic RVLM neurons may play an
      important role in determining the long-term level of sympathetic vasomotor tone
      and AP.

PMID- 12010202
TI  - Neurotransmitters in central cardiovascular regulation: glutamate and GABA.
AB  - 1. The role of the amino acids L-glutamate and GABA as neurotransmitters in
      central pathways regulating cardiovascular function is briefly summarized.

PMID- 12010203
TI  - Fred Hollows lecture. Eye care for the community.
AB  - Eye disease is a huge and largely unrecognized problem in our community,
      especially in the elderly. The Visual Impairment Project, an intensive
      epidemiological study conducted by the Centre for Eye Research Australia (CERA)
      from 1991 to 1999, determined the prevalence, causes and risk factors for eye
      disease in Australia, and helped identify a series of specific, often simple,
      steps and strategies to significantly reduce its impact. A distillation of CERA"s
      findings has highlighted the growing problem of eye disease in our community. In
      addition, CERA has joined with other interested bodies to form Vision 2020: the
      Right to Sight Australia. This partnership was established in response to the
      Global Initiative to Eliminate Avoidable Blindness by the year 2020 - Vision
      2020: the Right to Sight. This Global Initiative was established by the World
      Health Organization and the International Agency for the Prevention of Blindness.
      Vision 2020 Australia aims to be the peak body for all those involved in vision
      care in its broadest sense in Australia, and to put vision on the national
      agenda.

PMID- 12010204
TI  - Five-year outcome of correctable visual impairment: the Blue Mountains Eye Study.
AB  - This report aims to describe the outcome and socio-economic characteristics of
      older persons attending the Blue Mountains Eye Study (BMES) with persistent
      correct-able visual impairment (VI). The BMESI examined 3654 persons aged 49+
      during 1992-1994 and re-examined 2335 survivors during 1997-1999 (BMES II).
      Visual acuity was measured before and after standardized refraction. Participants
      had correctable VI if their better eye was visually impaired <6/12 before
      refraction (with distance glasses if worn) and was unimpaired after refraction.
      In BMES I,274 persons (7.5%) had correctable VI, of whom 127 returned to BMES II.
      Of this group of 127, 34 had persistent correctable VI and 74 were no longer
      impaired. Fewer persons with correctable VI returned and more died prior to BMES
      II, compared to persons with no or non-correctable VI. This study showed that
      persistent correctable impairment was more frequent with increasing age, among
      women, in those living alone, using community support services,or with a history
      of heart disease.

PMID- 12010205
TI  - Refractive changes following cataract surgery: the Blue Mountains Eye Study.
AB  - This study aimed to assess refractive changes following cataract surgery in
      subjects attending the Blue Mountains Eye Study baseline examinations in 1992
      1994 (3654 residents aged 49+ years),with 2335 (75.1%) survivors re-examined
      after 5 years. Participants underwent a standardized subjective refraction.
      History of cataract surgery was confirmed at examination and lens photograph
      grading. During follow up, 151 persons had cataract surgery (60 bilateral, 91
      unilateral). After exclusions, data from 198 eyes(93 right, 105 left) were
      analysed. The proportions of eyes achieving postoperative spherical equivalent
      refraction (SER) -0.25 to +0.25 D, -0.50 to +0.50 D, -0.75 to +0.75 D and -1.00
      to +1.00 D,were 32%, 44%, 60% and 74%,respectively. The magnitude and direction
      of refractive changes following cataract surgery were related to the preoperative
      refraction. Myopic eyes had a hyperopic shift (mean +2.76 D),hyperopic eyes a
      myopic shift (mean -1.77 D) and emmetropic eyes recorded little change (mean 
      0.13 D). Astigmatism (> or = 1.00 D cylinder) increased slightly postoperatively,
      from 47% to 56%, mostly 'against the rule' but with less oblique astigmatism.
      These findings indicate satisfactory refractive outcomes following current
      cataract surgery in a random older population.

PMID- 12010206
TI  - Socioeconomic status and incident cataract surgery: the Blue Mountains Eye Study.
AB  - The aim of this study was to assess whether socioeconomic status influenced the
      incidence of cataract surgery in a defined population of older Australians. The
      Blue Mountains Eye Study examined 3654 residents during 1992-1994, then 2334
      survivors (75.1%)during 1997-1999. Interviewers collected information on
      principal occupation, which was analysed using Australian Bureau of Statistics
      categories (stratified into four groups) and the Daniel Occupational Prestige
      Scale. Cataract surgical history was confirmed at both visits from clinical
      examinations. There were no statistically significant associations for any of the
      occupational categories with the 5-year incidence of cataract surgery. In
      summary, this study could not confirm any major socioeconomic associations with
      incident cataract surgery, supporting the view that cataract surgery is largely
      patient driven and that its primary incentive is patient benefit.

PMID- 12010207
TI  - High heritability of myopia does not preclude rapid changes in prevalence.
AB  - The aetiology of myopia is complex, but the major form of myopia results from an
      interplay between genetic factors and environmental influences. Although there
      are clear patterns of family inheritance and high heritability values in studies
      from all over the world,environmental factors are increasingly important in
      determining myopic outcomes in East Asia, and perhaps elsewhere. This is not
      paradoxical, as high heritability does not preclude strong environmental
      influences. The lower heritability values obtained from parent-offspring
      correlations in populations of East Asian origin where there are marked
      differences in the environmental exposures (education and urbanization) of
      parents and children, and where there has been a major shift in the population
      distribution of myopia, are consistent with this view. Despite the impact of
      environmental pressures in East Asia, there is evidence that parental myopia
      influences the position of their offspring within that new population
      distribution.

PMID- 12010208
TI  - Relationship between age and intraocular pressure: the Blue Mountains Eye Study.
AB  - This study aimed to assess the influence of age on intraocular pressure(IOP) in a
      general population. The Blue Mountains Eye Study assessed 3654 residents aged 49+
      years during 1992-1994. Intraocular pressure was measured using Goldmann
      applanation tonometry. Subjects with glaucoma, those currently on glaucoma
      medications and those with a history of cataract surgery were excluded. The IOP
      was reliably measured in 3260 subjects. Mean IOP was 16.0 mmHg with no
      significant difference found between men and women (P < 0.89). In univariate
      analyses, age was positively associated with IOP (P < 0.05). Systolic blood
      pressure (SBP) was strongly positively associated with IOP (P < 0.001). After
      adjusting for SBP, there was a trend for IOP to decrease with increasing age(P <
      0.051). After further adjusting for other potential confounders (diabetes,
      glaucoma family history and myopia), age was no longer significantly associated
      with intraocular pressure (P < 0.29). In summary,no evidence was found of an
      independent age affect on IOP.

PMID- 12010209
TI  - Central retinal vein occlusion in pseudoexfoliation of the lens capsule.
AB  - In surveying an extensive group of patients with unilateral pseudoexfoliation of
      the lens capsule certain interesting points emerged, particularly on the
      incidence of central retinal vein occlusion in this condition,and perhaps in
      glaucoma also. A total of 284 patients with unilateral pseudo-exfoliation of the
      lens capsule were examined clinically after an ophthalmic and general history
      were taken. Mean intraocular pressure (IOP) was 30.9 mmHg in the affected eye and
      18.1 mmHg in the unaffected eye. Central retinal vein occlusion occurred in 10
      affected eyes but no unaffected eyes and always in affected eyes with a rise in
      IOP. Average IOP in the affected eye with central retinal vein occlusion was 37.5
      mmHg (range 26-54 mmHg);in the unaffected fellow eye it was 18.0 mmHg (range 11
      28 mmHg). Although the process involved in producing pseudo-exfoliation of the
      lens capsule may contribute to the precipitation of central retinal vein
      occlusion, these findings suggest the rise in IOP is the more important cause.
      This may also be so in other forms of glaucoma.

PMID- 12010210
TI  - Reliability of computer-assisted retinal vessel measurementin a population.
AB  - The purpose of the study was to assess the intergrader and intragrader
      reliability of computer-assisted retinal vessel dia-meter measurement in a
      defined, community-based population. Retinal photographs from participants in the
      Blue Mountains Eye Study were digitized using standard techniques. A grader
      identified all retinal vessels located 0.5-1.0 disc diameter from the optic disc
      margin,and a computer program measured the width of these vessels. Intergrader
      and intragrader reliability was assessed on a random sub-sample of 184 and 97
      images, respectively, using quadratic weighted kappa(kappa) and correlation
      analysis (R2). Intergrader reliability was high for summary indices of retinal
      arteriolar (kappa = 0.85, R2 = 0.88)and venular (kappa = 0.90, R2 =
      0.90)diameters, and their ratio, the arteriole-to-venule ratio (kappa = 0.75, R2
      = 0.79).Intragrader reliability was also high, with kappa values ranging from
      0.80 to 0.93 and from 0.80 to 0.92 for graders 1 and 2, respectively. It is
      concluded that the retinal vessel diameters could be reliably measured using
      computer-assisted software and may be used for population-based research.

PMID- 12010211
TI  - Reading speed test for potential central vision measurement.
AB  - This study examines the validity and reliability of a reading speed test as a
      measure of potential central vision. Reading speed was calculated in words per
      minute (wpm) from the time taken to read 30 words of 1.20 logMAR size text.
      Scores were obtained from subjects with cataract (n = 48), macular disease(n =
      35), peripheral vision loss(n = 14) and normal eyes (n = 10). Subjects with
      macular disease (27.0 +/- 13.2 wpm) read much slower than subjects with cataract
      (91.9 +/- 13.6 wpm). Little difference was found between subjects with cataract,
      peripheral vision loss (91.5 +/- 14.7 wpm)and normal eyes (103.8 +/- 15.5 wpm).
      Repeat testing gave values within +/- 16% of reading speed. These results suggest
      that a reading speed test using large text could be useful as a potential central
      vision test in cataract patients.

PMID- 12010212
TI  - Assessing the sub-basal nerve plexus of the living healthy human cornea by in
      vivo confocal microscopy.
AB  - The purpose of the study was to perform quantitative analysis of the sub-basal
      epithelial nerve plexus of healthy, living human cornea,using real time in vivo
      confocal microscopy and the analySIS software system. The study was based on in
      vivo confocalmicrostructural analysis of 50 eyes of 50 subjects, divided into two
      age groups: group 1 (n = 25)25 +/- 5 years of age, and group 2 (n = 25) 70 +/- 5
      years of age. All subjects exhibited clinically healthy corneas. The overall
      nerve density was 632.35 +/- 287.57 microm/mm2 for group 1 and 582.39 +/- 327.13
      microm/mm2 for group 2. The mean fibre dia-meter was measured at 0.52 +/- 0.23
      microm for group 1 and at 0.56 +/- 0.27 microm for group 2. Beadings of the nerve
      fibres were recorded at a density of 213 +/- 123/mm for group 1 and 201 +/-
      192/mm for group 2. Establishing standards for normal nerve density and
      morphology of the living human cornea at different ages may be beneficial, both
      in early detection and follow up of various corneal diseases and in post-surgical
      management following corneal surgery.

PMID- 12010213
TI  - In vivo and ex vivo in situ confocal analysis of a rat model demonstrating
      transient 'epithelialization of the endothelium'.
AB  - The purpose of this study was to identify the in vivo microstructural
      characteristics of an animal model of 'epithelialization of the endothelium' that
      are similar in appearance to the in vivo confocal microscopical appearance of
      corneal endothelium previously thought to be diagnostic of irido-corneal
      endothelial syndrome, and correlate these observations with ex vivo in situ
      confocal microscopical analysis. A rat model (n = 8 eyes)of transient
      'epithelialization of the endothelium' resulting from superficial corneal trauma,
      was developed and analysed using in vivo confocal microscopy. One animal was
      killed at 48 hand the cornea was immuno-labelled and analysed, using ex vivo in
      situ confocal digital image reconstruction. Reversible 'epithelialization of the
      endothelium' was observed by in vivo confocal microscopy 48 h after superficial
      corneal trauma in all eight eyes. Ex vivo in situ analysis failed to demonstrate
      immunohistological characteristics of epithelialization. In vivo confocal
      microscopy is based on optical principles, and as a result various structural
      alterations may present with apparently identical characteristics that should be
      interpreted cautiously, on the basis of the presented clinicopathological
      observations.

PMID- 12010214
TI  - Gene expression of pro-inflammatory cytokines and chemokines in mouse eye
      infected with Pseudomonas aeruginosa.
AB  - Ocular infection with Pseudomonas aeruginosa triggers extensive host inflammatory
      response and corneal damage. The purpose of present study was to investigate the
      gene expression of pro-inflammatory mediators interleukin (IL)-1 beta, IL-6,
      tumour necrosis factor-alpha (TNF-alpha),macrophage inflammatory protein (MIP)-2
      and cytokine-induced neutrophil chemoattractant (KC) in the mouse eye challenged
      with P. aeruginosa. Scratched mouse corneas were infected with three phenotypes
      of P. aeruginosa individually. Total RNA was extracted from mouse eyes at 4 h, 8
      h,16 h and 24 h post-challenge. Single stranded cDNA was synthesized from total
      RNA by reverse transcription and then subjected to polymerase chain reaction
      (PCR) using specific primers for IL-1 beta, IL-6, TNF-alpha, MIP-2 and KC.
      Results revealed three patterns of cytokines and chemokines expression in
      response to ocular infection with three phenotypes of P. aeruginosa. Ocular
      infection with the invasive strain induced the highest levels of IL-1 beta, IL-6,
      MIP-2 and KC mRNA, followed by the infection with the cytotoxic strain. Ocular
      infection with the CLARE strain induced the lowest levels of IL-1 beta, IL-6, MIP
      2 and KC mRNA. The expression of TNF-alpha mRNA was very low and irregular
      following P. aeruginosa challenge. These data indicate that over-expression of
      pro-inflammatory cytokines and chemokines may represent a vigorous immune
      response and therefore may contribute to corneal damage during P. aeruginosa
      infection.

PMID- 12010215
TI  - Effects of post-mortem delay and storage duration on the expression of GFAP in
      normal human adult retinae.
AB  - Glial fibrillary acidic protein (GFAP) is an established marker of retinal glia
      and has been shown to be modulated by several cytokines and retinal pathology.
      The influence of a number of factors, including post-mortem delay, storage
      duration and retinal pathology, on the distribution and morphology of macroglia
      and GFAP antigenicity was examined in human retina. The effects of these
      parameters on GFAP expression were estimated using immunohistochemistry, confocal
      microscopy and image analysis. Changes in expression of antigenicity were
      analysed in human retinal cryosections at three levels: constitutive,aberrant and
      total. The results indicated that short-term and long-term storage duration had
      no significant effect on GFAP immunoreactivity at all three levels of expression
      (P > 0.2).However, a significant increase in GFAP immunoreactivity and
      distribution at all three levels of expression was associated with prolonged post
      mortem delay (> 30 h) (P < 0.05). This study highlights the importance of
      rigorous matching of post-mortem delay between control specimens in histological
      studies of human retinae. The study further demonstrates the utility of Eye Bank
      retinae fixed and stored in 2% paraformaldehyde, provided that appropriate
      controls are applied.

PMID- 12010216
TI  - Ethanol effects on volitional versus reflexive saccades.
AB  - The effects of a moderate alcohol dose on reflexive and volitional saccades were
      compared. Healthy male subjects (n = 17) made horizontal reflexive saccades,
      antisaccades and self-paced saccades before and after the ingestion of a body
      weight-related dose of alcohol. At a mean blood alcohol concentration of 0.044%,
      reflexive saccade latency significantly increased although accuracy remained
      unimpaired at each target amplitude. No significant ethanol effects were noted
      for antisaccade accuracy and latency. Antisaccade error rates decreased
      significantly, likely demonstrating a learning effect. The mean rate of self
      paced saccades did not significantly change post-ethanol and their accuracy was
      also unimpaired. All saccades share a final common pathway for their execution.
      It thus seems reasonable to propose that ethanol modulated connections between
      the posterior parietal cortex and superior colliculus to increase reflexive
      saccade latency. Higher-order paradigms, which require inhibition and are
      mediated by frontal areas, might be impaired at greater blood alcohol
      concentrations.

PMID- 12010217
TI  - The flash-lag effect and equiluminance.
AB  - An object briefly flashed adjacent to the path of another moving object appears
      to spatially lag the moving object in the direction of its motion: the 'flash-lag
      effect'. A simple differential lag model account of this effect suggests that it
      occurs because the moving object activates motion detectors in the faster
      magnocellular pathway, whereas the flashed object does not. This model was tested
      by reducing M-pathway involvement using isoluminant stimuli. All four
      participants, who were university undergraduate students, were exposed to eight
      conditions, involving all possible combinations of moving and flashing objects
      coloured either white or green, shown against either a grey or a black
      background. Green objects were equiluminant with the grey background. The
      magnitude of the flash-lag effect was found using the method of constant stimuli.
      No reliable support was found for the hypothesis that equiluminance of the moving
      object reduces the flash-lag effect. Instead an interaction was found where there
      was an effect of equiluminance on the flash, but only when the moving object was
      not equiluminant. Such data is problematic for this and other simple differential
      lag models of the flash-lag effect.

PMID- 12010218
TI  - Effects of optical defocus and spatial contrast on anterior chamber depth in
      chicks.
AB  - The goal of this study was to investigate the effect of optical defocus and
      spatial contrast on refractive development and, in particular,on anterior chamber
      growth. Ninety chicks were raised from day 4-10 post-hatching wearing monocular
      lenses (+/-10 Dor 0 D), in an environment with either high, low or no spatial
      contrast patterns: 30%, 6% or 0% contrast, respectively. At day 10, the chicks'
      refractive state and ocular components were assessed using retinoscopy and A-scan
      ultrasonography. Ocular defocus resulted in sign-dependent significant
      differences in refractive error, axial length and vitreous chamber depth. Lens
      wear also led to significant spatial contrast dependent changes in anterior
      chamber depth. Varying ambient spatial contrast in the chick's environment did
      not inhibit emmetropization processes; however, anterior chamber growth was
      particularly susceptible to changes in spatial contrast.

PMID- 12010219
TI  - Temporal processing of global and local information varies with global
      precedence.
AB  - The concept of global precedence, which suggests that the global aspect of a
      scene is processed more rapidly than local details, was examined using the
      attentional blink paradigm. Eighteen adult subjects observed multiple sequences
      of complex global-local letter figures to see whether the attentional blink
      duration would be affected by the visual angle size of the stimulus. Within each
      sequence, the subject was directed to identify either a global or local red
      target letter and to detect whether a global or local probe letter (X) was
      presented in the sequence following the target letter. Stimuli were presented at
      three different sizes. Results showed significantly higher probe detection rates
      for global probes than for local at small stimulus sizes. However, using large
      stimulus sizes, mean correct probe detection was significantly higher in
      conditions requiring local attention compared to global. No significant
      difference in probe detection performance was observed between global and local
      conditions at medium stimulus sizes. The results suggest that the rate of visual
      information processing varies according to the visual angle of the particular
      information. The results support the suggestion that the precedence of
      information is an important factor in the temporal processing of global-local
      information.

PMID- 12010220
TI  - Normal readers have an upper visual field advantage in change detection.
AB  - The ability to detect change has not been well studied in children.A research
      paradigm was used involving search for a change made to one of four letter
      targets, presented twice, with a gap of 250 ms.Sixty-one schoolchildren, aged 7.3
      - 12.9 years,participated in the study. The duration of the first presentation
      was such that each child was detecting change at a rate of 71% correct. The mean
      duration was 0.91 s (SD = 0.58 s),with older children not significantly faster in
      detecting change. In the second phase, using the duration established in the
      first phase, the effect of cue condition on detection was studied. An upper
      visual field advantage for change detection was clearly evident for un-cued
      trials. The most likely explanation derives from the masking produced by the
      reappearance of the four targets, which interferes with the process of change
      detection. The greater dorsal pathway representation of the lower visual field
      implies greater masking there, yielding better change detection in the upper
      visual field.

PMID- 12010221
TI  - Separation of contour and area dependent components in the first and second order
      kernels of the multifocal pattern appearance evoked potential.
AB  - The non-linearities of the diffuse flash visual evoked potential (VEP) have been
      shown to generate separable waves corresponding to Magnocellular and
      Parvocellular contributions. The authors wished to investigate whether, under
      conditions of isoluminance, the chromatic pattern appearance VEP shows waveforms
      that are related to both the processing of contours (the pattern) and the
      processing of the diffuse stimulation (from the area lying between the contours).
      The VERIS multifocal system was used to record monocular VEP. Standard 2-ring, 3
      ring, 5-ring and 7-ring VERIS pattern stimuli were employed with a cardboard
      circular aperture used to blank the stimulus monitor to a 9-cm diameter field.
      The results for four subjects were recorded. The first order kernel responses
      showed a significant increase in amplitude with total contour length. In
      comparison, the amplitudes of the first and second slices of the second order
      kernel did not increase with contour length. It appears that the contour
      dependent component has negligible non-linear components. It is proposed that the
      constant, non-zero responses of the higher order kernel components reflects
      contributions from the diffuse chromatic VEP.

PMID- 12010223
TI  - The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate
      crystallization and other factors associated with renal stone formation.
AB  - OBJECTIVE: To evaluate the effect of an aqueous extract of Phyllanthus niruri
      (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion
      of endogenous inhibitors of lithogenesis, citrate, magnesium and
      glycosaminoglycans (GAGs). MATERIALS AND METHODS: The effect of chronic (42 days)
      administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of
      urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into
      the bladder of adult male Wistar rats. The animals were divided into four groups:
      a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and
      CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for
      biochemical analysis and the determination of urinary excretion of citrate,
      magnesium and GAGs. The animals were then killed and the calculi analysed.
      RESULTS: The creatinine clearance or urinary and plasma concentrations of Na+,
      K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction
      of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix
      calculus and reduced the number of stone satellites compared with the group
      receiving water. The calculi were eliminated or dissolved in some treated animals
      (three of 22). The urinary excretion of citrate and magnesium was unaffected by
      Pn treatment. However, the mean (sd) urinary concentration of GAGs was
      significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine,
      than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In
      contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at
      48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g
      calculus. CONCLUSION: These results show that Pn has an inhibitory effect on
      crystal growth, which is independent of changes in the urinary excretion of
      citrate and Mg, but might be related to the higher incorporation of GAGs into the
      calculi.

PMID- 12010224
TI  - Risk factors for developing renal stones in inflammatory bowel disease.
AB  - OBJECTIVE: To correlate renal calculi and other clinical factors with urinary
      biochemical analytes in patients with inflammatory bowel disease, and to
      investigate the relative importance of hyperoxaluria (associated with fat
      malabsorption) or reduced stone inhibitors in the development of calculi in these
      patients. PATIENTS, SUBJECTS AND METHODS: Samples were obtained from 25 patients
      with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 17 normal subjects
      (controls). Evidence for the presence of renal calculi was obtained from plain
      films, ultrasonography or intravenous urography. Urine oxalate and citrate were
      analysed using commercial enzymatic assays; magnesium was measured using atomic
      absorption and other analytes assayed using standard methods on automated
      analysers. RESULTS: Renal calculi were found in two patients with CD and in none
      with UC. Hyperoxaluria was present in 36% of patients with CD but was absent in
      those with UC. Analysis of covariance showed an association between low urinary
      citrate/creatinine ratio and renal stones (P=0.02), and between a combined
      urinary citrate and magnesium deficit relative to calcium, as expressed in the
      CMC index ((citratexmagnesium)/calcium), and renal stones (P=0.017). Changes in
      urinary calcium, oxalate, urate, magnesium or the calcium oxalate index were not
      associated with the presence of stones. There was no independent relationship
      between any clinical factor and the presence of stones. CONCLUSION: Lower urinary
      concentrations of magnesium and citrate (stone inhibitors), relative to calcium
      (stone promoter; the CMC index) may be more important in lithogenesis in
      inflammatory bowel disease than is hyperoxaluria. In patients with a functioning
      colon, a low CMC index may predict likely stone-formers; this requires a
      prospective evaluation. Avoiding low urinary levels of magnesium and citrate may
      aid in preventing and treating renal calculi.

PMID- 12010225
TI  - Association of dietary fatty acids with urinary oxalate excretion in calcium
      oxalate stone-formers in their fourth decade.
AB  - OBJECTIVE: To examine the influence of the dietary intake of fatty acid on
      urinary oxalate excretion in calcium oxalate stone-formers in their fourth
      decade, as previous reports show that animal fat intake is associated with
      urinary oxalate excretion. PATIENTS AND METHODS: The dietary intake of 58
      idiopathic stone-formers in their fourth decade was recorded using the dietary
      record method. The patients collected 24-h urine samples at home and their
      urinary oxalate excretion was measured in a clinical biochemistry laboratory. The
      results were used to determine the relationship between the dietary intake of
      fatty acids and urinary oxalate excretion. Associations between urinary oxalate
      excretion and dietary contents of animal fat, animal protein and various fatty
      acids were assessed using Spearman's correlation coefficient and multiple
      regression. RESULTS: The dietary content of arachidonic acid was positively
      correlated with urinary oxalate excretion, as assessed by univariate and
      multivariate analysis. CONCLUSION: The association between arachidonic acid and
      oxalate excretion suggests that arachidonic acid increases the intestinal
      absorption of oxalate and increases the clearance of oxalate in the kidneys.

PMID- 12010226
TI  - Time-dependent changes of resistive index in acute renal obstruction during
      nonsteroidal drug administration.
AB  - OBJECTIVE: To evaluate Doppler ultrasonography (DUS) and assess time-dependent
      changes of the renal resistive index (RI) in acute unilateral renal obstruction
      during treatment with nonsteroidal analgesic for the relief of renal colic.
      PATIENTS AND METHODS: In 31 patients with symptoms of renal colic, treated with
      ketoprofen, unilateral obstruction was confirmed by intravenous urography. The
      patients were divided into four groups according to the duration of their
      symptoms, i.e. < 23 h, 24-47 h, 48-72 h and > 72 h. In each patient, the RI was
      measured over the arcuate, segmental and renal arteries of both kidneys using
      DUS. The values obtained in the obstructed kidney were compared with those for
      the contralateral kidney. RESULTS: The mean (sd) RIs for all 31 patients were
      0.71 (0.05) for the obstructed and 0.60 (0.05) for the contralateral kidney (P <
      0.001), the mean difference (dRI) being 0.12 (0.07). In those with obstruction
      for < 23 h the mean RI of the obstructed kidney was 0.70 (0.05) and of the
      contralateral healthy one 0.62 (0.07). Values of RI were similar in the group
      with obstruction for 24-47 h and 48-71 h. In those with obstruction for > 72 h
      the mean RI of the obstructed kidney was 0.69 (0.07) and of the contralateral one
      0.60 (0.04), with a dRI of 0.09 (P < 0.005). The RI was 87% sensitive and 90%
      specific for detecting renal obstruction. CONCLUSION: Although the patients were
      given ketoprofen, their mean RI for the obstructed kidney remained above the
      discriminatory threshold (> 0.70) during the first 71 h of obstruction. Only in
      those obstructed for > 72 h was the mean RI on the obstructed side slightly below
      the threshold, but the difference between the kidneys was significant. The
      measurement of RI is a reliable diagnostic method for detecting acute renal
      obstruction. With a longer duration of symptoms, the difference in RI between the
      kidneys becomes clinically more relevant.

PMID- 12010227
TI  - Non-secretor status is associated with female acute uncomplicated pyelonephritis.
AB  - OBJECTIVE: To retrospectively analyse the secretor status in women with acute
      uncomplicated pyelonephritis, as non-secretors of histo-blood group antigens are
      reportedly at risk of recurrent urinary tract infections (UTIs). PATIENTS AND
      METHODS: The study included 245 women who had been diagnosed as having acute
      uncomplicated pyelonephritis in affiliated hospitals over the past 5 years. All
      women were sent antiseptic swabs, to collect saliva, and a questionnaire to
      survey their past UTI episodes and menstrual status. Responses with written
      informed consent were obtained from 106 women (median age 50.5 years, range 17
      85). The secretor status was determined using the haemagglutination inhibition
      assay from the saliva on the swabs. RESULTS: Forty-four (41%) of the women were
      non-secretors, a significantly higher frequency than in the (control) Japanese
      population (217 of 960, 22.6%; P< 0.001). The incidence of non-secretors was
      significantly higher (P < 0.01) in premenopausal (26 of 46, 57%) than in
      postmenopausal women (18 of 60, 30%). CONCLUSION: These results suggest that non
      secretor status is associated with a genetic susceptibility to acute
      uncomplicated pyelonephritis, especially in premenopausal women.

PMID- 12010228
TI  - Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo
      controlled study in men.
AB  - OBJECTIVE: To investigate the efficacy and safety of oral desmopressin in the
      treatment of nocturia in men. PATIENTS AND METHODS: Men aged >/=18 years with
      verified nocturia (>or=two voids/night) and nocturnal urine production greater
      than their maximum functional bladder capacity were recruited. A 3-week dose
      titration phase established the optimum desmopressin dose (0.1, 0.2 or 0.4 mg).
      After a 1-week 'washout' period, patients who responded in the dose-titration
      period were randomized to receive the optimal dose of desmopressin or placebo in
      a double-blind design for 3 weeks. RESULTS: In all, 151 patients entered the
      double-blind period (86 treated with desmopressin, 65 with placebo). In the
      desmopressin group 28 (34%) patients and in the placebo group two (3%) patients
      (P<0.001) had fewer than half the number of nocturnal voids relative to baseline;
      the mean number of nocturnal voids decreased from 3.0 to 1.7 and from 3.2 to 2.7,
      respectively, reflecting a mean decrease of 43% and 12% (P<0.001). The mean
      duration of the first sleep period increased by 59% (from 2.7 to 4.5 h) in the
      desmopressin group, compared with an increase of 21% (from 2.5 to 2.9 h) in the
      placebo group (P<0.001). The mean nocturnal diuresis decreased by 36% (from 1.5
      to 0.9 mL/min) in the desmopressin group and by 6% (from 1.7 to 1.5 mL/min) in
      the placebo group (P<0.001). The mean ratio of night/24-h urine volume decreased
      by 23% and 1% (P<0.001), and the mean ratio of night/day urine volume decreased
      by 27% and increased by 3% (P<0.001) for the desmopressin and placebo groups,
      respectively. In the double-blind treatment period, similar numbers of patients
      had adverse events; 15 (17%) patients in the desmopressin and 16 (25%) patients
      in the placebo group. Most adverse events were mild. Serum sodium levels were
      <130 mmol/L in 10 (4%) patients and this occurred during dose-titration.
      CONCLUSIONS: Orally administered desmopressin is an effective and well-tolerated
      treatment for nocturia in men.

PMID- 12010229
TI  - Female urodynamics and lower urinary tract infection.
AB  - OBJECTIVES: To determine the incidence of unsuspected urinary tract infection
      (UTI) before cystometry, to evaluate reports of a greater tendency to abnormal
      cystometry in the presence of asymptomatic bacteriuria, and to determine the
      incidence of iatrogenic significant bacteriuria after cystometry. PATIENTS AND
      METHODS: A prospective study was carried out in the gynaecology department of a
      district general hospital in collaboration with the medical microbiology
      department of a university teaching hospital. The period of investigation was 1
      year and the study population was a sample of women undergoing urodynamic
      investigations during this period. Data were collected on age, menopausal status,
      parity, cystometric diagnosis and voiding dysfunction. RESULTS: In all, 117
      patients provided a urine sample before cystometry; 12 of these patients had a
      positive culture, giving an incidence of 10.3% for unsuspected asymptomatic
      bacteriuria before cystometry. There was a significant association between age
      and the presence of UTI before cystometry (P = 0.003) and between this UTI and
      sensory urgency (P = 0.01). There was no similar significant association with
      detrusor instability or genuine stress incontinence. Nineteen of the 97 patients
      who had negative bacteriology before cystometry had a positive urine culture
      afterward. Compared with patients who had a negative sample, there was no
      significant association with age, parity, menopausal status, abnormal cystometry
      or voiding dysfunction. CONCLUSION: These results do not support a policy of
      universal screening for bacteriuria before urodynamic investigation. Asymptomatic
      bacteriuria did not influence the urodynamic outcome except in patients with
      sensory urgency. However, we recommend that screening and treatment be considered
      individually in older women who are being investigated for irritative bladder
      symptoms. About 20% of the present patients developed UTI after the urodynamic
      investigation. This information should be included in the counselling before
      urodynamic investigation and should be incorporated into the patient information
      leaflet as part of good clinical practice.

PMID- 12010230
TI  - Delay and survival in bladder cancer.
AB  - OBJECTIVE: To assess in detail and evaluate the effect on survival of delays in
      the diagnosis and treatment of cancer (which might lead to a worse prognosis),
      dividing the delay from onset of symptoms to first treatment into several
      components, comprising patient delay, general practitioner (GP) delay, and two or
      more periods of hospital delay. PATIENTS AND METHODS: Data were prospectively
      collected on 1537 new cases of urothelial cancer in the West Midlands from 1
      January 1991 to 30 June 1992. Death information was obtained from the West
      Midlands Cancer Intelligence Unit and censored at 31 July 2000. The influence of
      delay times on survival was explored. RESULTS: The median delay from onset of
      symptoms to GP referral was 14 days (Delay 1), from GP referral to first hospital
      attendance was 28 days (Delay 2), and from first hospital attendance to first
      transurethral resection of bladder tumour was 20 days (Delay 3). The median
      hospital delay (Delay 2 + 3) was 68 days and the median total delay (Delay 1 + 2
      + 3) was 110 days. Patients with a shorter Delay 1 had a lower tumour stage and a
      5% better 5-year survival. Patients with a shorter hospital delay had worse
      survival; total delay had no effect on survival. CONCLUSIONS: There was
      significantly better survival for patients referred to hospital within 14 days of
      the onset of symptoms. The relationship between delay and survival in bladder
      cancer is complex. Hospital delays may be influenced more by comorbidity than by
      the characteristics of the tumour. However, the adverse effects of delay seem to
      be most pronounced for patients with pT1 tumours.

PMID- 12010231
TI  - Is mechanical bowel preparation necessary in patients undergoing cystectomy and
      urinary diversion?
AB  - OBJECTIVE: To compare the surgical outcome in patients with or with no bowel
      preparation before cystectomy and ileal conduit urinary diversion, specifically
      assessing local and systemic complications. PATIENTS AND METHODS: All patients
      undergoing cystectomy and ileal conduit urinary diversion between January 1991
      and December 1999 were assessed retrospectively. Twenty-two receive no bowel
      preparation (group 1) and were compared with 64 who had (group 2). Patients had
      similar demographic characteristics, stage and grade of tumour. Patients in group
      2 received a standard 4-day bowel preparation and group 1 received no lavage or
      enemas. All patients underwent a standard iliac and obturator lymph node
      dissection, and cystoprostatectomy or anterior exenteration and ileal conduit
      urinary diversion. All patients received intraoperative metronidazole and
      gentamicin intravenously, and two further doses after surgery. RESULTS: Deaths
      after surgery were comparable in the two groups (two in group 1 and four in group
      2) and the incidence of wound infection was similar (three and seven,
      respectively). There were no significant differences between the respective
      groups for fistula and anastomotic dehiscence (two and six) or sepsis (three and
      six). Group 2 had a higher incidence of wound dehiscence (one) than in group 1
      (none). The incidence of prolonged postoperative ileus was lower in group 1 (one
      vs 12), as was the length of hospital stay (31.6 days vs 22.8 days). CONCLUSIONS:
      Bowel preparation had no advantage for the surgical outcome but it increased the
      length of hospital stay.

PMID- 12010232
TI  - The clinical utility of the prostate specific membrane antigen reverse
      transcription/polymerase chain reaction to detect circulating prostate cells: an
      analysis in healthy men and women.
AB  - OBJECTIVE: To evaluate the overall specificity of nested reverse transcriptase
      polymerase chain reaction (RT-PCR) to detect prostate-specific membrane antigen
      (PSM) mRNA in peripheral blood samples of healthy donors. SUBJECTS AND METHODS:
      Peripheral blood samples were taken from 60 healthy blood-donors (30 men and 30
      women aged < 50 years) and analysed for PSM-mRNA using nested RT-PCR (in 'hot
      start' conditions and confirmed using nested EcoRI restriction enzyme). Intron
      spanning primer pairs specific for human PSM were deduced from the GenBank
      sequence (M99487) using gene software. The outer primer pair for PSM was: fwd:
      1368 5'-TCACCGGGACTCATGGGTGT-3'; reverse: 1860 5'-GCCTGAAGCAATTCCAAGTCGG-3'.
      Inner primer pair for PSM was: fwd: 1480 5'-AAGGAAGGGTGGAGACCTAG-3'; reverse: 5
      ACTGAACTCTGGGGAAGGAC-3'. The integrity of cDNAs was checked using primer pairs
      specific for the housekeeping gene beta-actin. The specificity and false-positive
      rate were calculated assuming that the underlying prostate cancer incidence was
      nil. RESULTS: The first PCR was negative for all samples (100% specificity; 0%
      false-positive rate). The nested PCR detected 23 positive samples (23/60, 38%)
      with an overall specificity of 62% (false positive rate, 38%). CONCLUSION: Nested
      RT-PCR of PSM-mRNA in peripheral blood is highly unspecific. Its clinical utility
      in the management of prostate cancer must be low. Further development is needed
      of quantitative RT-PCR, primers that identify prostatic PSM or another prostate
      specific marker gene to differentiate PSM mRNA from circulating prostate cells
      and from non-prostatic tissues.

PMID- 12010233
TI  - Anterior prostate cancer: is it more difficult to diagnose?
AB  - OBJECTIVE; To determine whether anterior prostatic tumours are adequately sampled
      using the Stamey sextant protocol, as a fifth of prostate cancers are anterior in
      distribution at radical prostatectomy. MATERIALS AND METHODS: All tumours (62)
      with an anterior distribution (>or=75% of the tumour anterior to the urethra) on
      radical prostatectomy whole-mounts, and in which the number and results of the
      sextant biopsies were available, were extracted from a prostate cancer database.
      Sixty-one posterior tumours (>or=75% of the malignant tissue posterior to the
      urethra) and their corresponding sextant biopsies were also retrieved for
      comparison. The number of biopsy sessions, the number of cores involved and the
      summated tumour length were recorded, together with the prostate gland weight,
      the tumour volume and the site of >or=75% of tumour in the superior-inferior
      axis. RESULTS: Anterior tumours required significantly more biopsy sessions to
      diagnose prostate cancer than posterior neoplasms (anterior, one set 47; > one
      set 15; posterior, one set 57; > one set, four, P=0.007). Anterior tumours had
      fewer cores with tumour involvement and less summated tumour length than had
      posterior cancers. The mean (sd) number of positive cores was; anterior 1.8
      (1.01), posterior 2.50 (1.30) (P=0.001); the summated tumour length was; anterior
      5.05 (4.10) mm, posterior 9.25 (7.80) mm (P<0.001). There was no significant
      difference in gland weight (mean anterior 43.8 g; posterior 48.3 g, P=0.3) or
      tumour volume (mean anterior 1.85 mL; posterior 1.49 mL, P=0.11) between the
      groups. There was no significant difference between the incidence of anterior and
      posterior neoplasms with respect to their position in the superior-inferior axis
      (P=0.96). CONCLUSIONS: Anterior prostate tumours account for 21% of all prostate
      cancers. They more often require multiple sets of sextant biopsies for diagnosis,
      and yield smaller areas of cancer on core biopsies than do posterior tumours in
      glands of similar weight and tumour volume. If prostate cancer is suspected
      clinically but biopsies are negative, targeting the anterior gland at subsequent
      prostatic biopsy should be considered.

PMID- 12010234
TI  - Penile fracture in Kermanshah, Iran: the long-term results of surgical treatment.
AB  - OBJECTIVE: To determine the long-term outcome of the surgical management of
      penile fracture. PATIENT AND METHODS: In all, 170 patients (mean age 27 years, sd
      13, median 24, range 13-80) with penile fracture undergoing surgery between April
      1990 and December 2000 were reviewed. In addition to a history, physical
      examination and hospital records, long-term potency (> 6 months after surgery)
      was evaluated using the patients' self-rated assessment of erectile function and
      the International Index of Erectile Function (IIEF-5) questionnaire. The results
      were correlated with the surgical findings. A control group of 200 men also self
      rated their erectile function and completed the IIEF-5. For those patients who
      presented with their partners, the partner's satisfaction with erections was also
      evaluated. The mean (median, range) follow-up after injury was 53 (61, 6-132)
      months. RESULTS: Satisfactory and painless erectile function with a soft straight
      penis was reported by 162 patients (95.2%). Complications occurred in eight
      patients (4.7%), of whom seven developed a mild (four) to moderate (three) penile
      curvature; five had penile nodules and four reported mild paresthesia over the
      scar line. Mild and moderate erectile dysfunction (ED) was reported by five and
      three patients, and four and five of controls, respectively (P > 0.05). There was
      no difference between the surgical findings of six patients with complications
      and those of the remaining 162. However, in the two remaining cases extensive
      injury was associated with moderate ED after surgery. Of eight patients with ED,
      seven responded to intracavernosal injection with papaverine/phentolamine.
      Erectile function returned within a mean (range) of 2 (1-5) days and coitus was
      possible approximately 2 weeks after the repair. Of the patients' partners, 94.1%
      reported satisfaction with erections and only one reported de novo dyspareunia.
      Penile fracture was not associated with an increased risk of ED (odds ratio 0.95;
      95% confidence interval, 0.35-2.53). In sexually active participants, the mean
      (sd, range) IIEF-5 score for 162 patients was 23.2 (2.7, 13-25) and not
      significantly different from that for the 194 controls, at 22.8 (2.1, 11-25).
      However, patients had higher scores than controls for erectile firmness and
      maintenance ability (P < 0.05). CONCLUSIONS: Surgery for a fractured penis is
      safe and effective, restoring erectile function to that of controls. Surgical
      treatment is very satisfactory for patients and partners. Considering these
      encouraging results, surgical intervention is strongly recommended.

PMID- 12010235
TI  - Oral propionyl-l-carnitine and intraplaque verapamil in the therapy of advanced
      and resistant Peyronie's disease.
AB  - OBJECTIVE: To ascertain whether oral propionyl-l-carnitine combined with
      intraplaque verapamil is a useful therapy for advanced or resistant Peyronie's
      disease. PATIENTS AND METHODS: The combined drugs were assessed in two studies.
      In the first, 60 patients with advanced Peyronie's disease, diagnosed using
      accepted definitions, were randomized in two subgroups treated with verapamil
      intraplaque infiltration (10 mg weekly for 10 weeks) plus a 3-month
      administration of propionyl-l-carnitine (2 g/day), or verapamil infiltration plus
      oral tamoxifen (40 mg/day) for 3 months. In the second study, 15 patients with
      resistant Peyronie's disease (progression despite previous therapy) received
      verapamil plus propionyl-l-carnitine. The differences between subgroups or
      between the variables before and after therapy were compared using analysis of
      variance or the chi-squared test. RESULTS: In the first study, the reduction in
      pain was the same in both subgroups. Propionyl-l-carnitine plus verapamil
      significantly reduced penile curvature, plaque size, cavernosal artery end
      diastolic velocity, the need for surgery and disease progression, and increased
      the International Index of Erectile Function score and resistivity index of the
      cavernosal arteries. Tamoxifen plus verapamil had none of these effects. No drug
      combination affected the peak systolic velocity. Patients receiving verapamil had
      no side-effects but those taking tamoxifen did. In the second study propionyl-l
      carnitine and verapamil modified the disease patterns as in the first and no
      patient had side-effects. CONCLUSION: The combination of propionyl-l-carnitine
      and verapamil can be considered the therapy of choice for advanced and resistant
      Peyronie's disease.

PMID- 12010236
TI  - Intracavernosal injection therapy with and without sexological counselling in men
      with erectile dysfunction.
AB  - OBJECTIVE: To compare the acceptance of and satisfaction with intracavernosal
      injection (ICI) therapy with and without sexological counselling in men with
      erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective randomized
      study, men were alternately assigned to ICI without sexological counselling (-SC)
      or with sexological counselling (+SC). In all, 70 patients were included, i.e. 35
      in each group; 57 (28 -SC, 29 +SC) were interviewed by telephone after a mean
      follow-up of 11.3 months to determine their use of ICI and reasons for
      discontinuing. RESULTS: There were no differences between the groups in
      discontinuation of ICI (overall 30%), in reasons for discontinuing ICI (24% did
      so because of the return of spontaneous erections) or in sexual functioning.
      CONCLUSION: There was no positive contribution from additional sexological
      counselling but extensive information and support by the urologist seems to be
      sufficient, resulting in a high acceptance rate of ICI. The discontinuation rate
      (30%) is one of the lowest reported.

PMID- 12010237
TI  - Apoptosis-related proteins in the testes of infertile men with varicocele.
AB  - OBJECTIVES: To assess immunohistochemically the expression of apoptosis-related
      proteins in the testes of infertile men, to determine which of these proteins
      were related to hypospermatogenesis, as a previous report suggested that
      apoptosis was suppressed in infertile men with varicocele. MATERIALS AND METHODS:
      The expression of Bcl-2, Bax, caspase-1 (ICE) and caspase-3 (CPP32) were examined
      in bilateral testicular specimens from 26 infertile men with varicocele and six
      normal testicular specimens, using the avidin-biotin-peroxidase complex method.
      Clinical variables were also assessed. RESULTS: Bax, ICE, and CPP32 were
      expressed in germ cells, while Bcl-2 was not. Differences in staining in left or
      right testes were not significant. In both testes of infertile patients with
      varicocele, significantly fewer germ cells stained for CPP32 than in controls (P
      < 0.001). For Bax and ICE, total germ cell staining was similar between these
      groups. Staining was less frequent in infertile patients for both CPP32 and ICE
      when the analysis was restricted to spermatogonia. Serum luteinizing hormone
      levels correlated positively with CPP32 staining (P = 0.0457). CONCLUSIONS: The
      reduced expression of CPP32 participates in regulating apoptosis in the testes of
      infertile men with varicocele.

PMID- 12010238
TI  - The testis: what did he witness?

PMID- 12010239
TI  - 18F-fluoro-2-deoxyglucose-positron emission tomography in the evaluation of
      nonseminomatous germ cell tumours at relapse.
AB  - OBJECTIVES: To compare the performance of 18F-fluoro-2-deoxyglucose-positron
      emission tomography (FDG-PET) and computed tomography (CT) in the follow-up of
      nonseminomatous germ cell tumours (NSGCT) in the retroperitoneum. PATIENTS AND
      METHODS: FDG-PET was used 25 times in 15 patients diagnosed with NSGCT. At the
      time of diagnosis five patients each were in stage I, II and III. Five patients
      had pure embryonal carcinoma, two had yolk sac tumours, one choriocarcinoma and
      seven had mixed tumours. RESULTS: Eleven patients either presented with
      retroperitoneal disease or this did not disappear after chemotherapy. The results
      of both examinations coincided in 18 cases and were contradictory in the other
      seven, the difference being statistically significant (P=0.042). CONCLUSION: In
      these patients FDG-PET detected the retroperitoneal relapse of NSGCT, in advanced
      stages treated with surgery plus chemotherapy, earlier than did CT; it also
      detected the presence of mature teratoma in residual retroperitoneal masses more
      accurately than CT. More extensive trials are needed before making conclusions
      about FDG-PET imaging as a routine method for NSGCT.

PMID- 12010240
TI  - The relationship between desmopressin treatment and voiding pattern in children.
AB  - OBJECTIVE: To collect data on voiding patterns at baseline (no treatment) and
      during short-term desmopressin treatment, with special reference to the
      functional and the mean bladder capacity. PATIENTS AND METHODS: The study
      included 120 children (aged 6-16 years) with monosymptomatic nocturnal enuresis.
      While at home they recorded their fluid intake and diuresis in two separate
      periods, i.e. 2 weeks as a baseline registration and another 2 weeks during
      desmopressin titration. On four study days the children recorded the time and
      volume of all voids and of fluid intake. From the diaries their functional and
      mean bladder capacities, 24-h diuresis and day/night ratio of diuresis were
      determined. RESULTS: The mean 24-h diuresis was significantly lower during short
      term desmopressin treatment. In most of the enuretics the mean day/night ratio
      increased on desmopressin treatment. The mean functional and mean bladder
      capacities were unaffected by desmopressin. Those not responding had bladder
      capacities of approximately 100 mL less than full responders. Regardless of
      response, practically all the enuretics in the study had a smaller functional
      bladder capacity than expected for their age. Among responders the morning void
      was significantly larger than the following voids during the day, and among non
      responders the fourth void was significantly larger than the previous voids in
      the day. Desmopressin treatment did not influence these volumes significantly.
      CONCLUSIONS: Short-term desmopressin treatment does not affect functional and
      mean bladder capacity; 24-h urine production was reduced significantly (P<0.01)
      during desmopressin treatment.

PMID- 12010241
TI  - The outcome of voiding dysfunction managed with clean intermittent
      catheterization in neurologically and anatomically normal children.
AB  - OBJECTIVE: To describe the tolerability and efficacy of clean intermittent
      catheterization (CIC) in the management of dysfunctional voiding in patients who
      are neurologically and anatomically normal. PATIENTS AND METHODS: The medical
      records were reviewed in 23 patients (16 girls, mean age 9 years, range 6-14.5,
      and seven males, mean age 8 years, range 5-20.5) with urinary incontinence and/or
      urinary tract infection (UTI) who were offered CIC because they had a large
      postvoid residual urine volume (PVR). All had extensive instruction before
      starting CIC. All patients underwent urodynamic studies, and urinary and fecal
      elimination habits were recorded. Detrusor hyperactivity, when present, was
      treated with anticholinergic medication. The follow-up evaluation included
      tolerance of CIC, continence status and the incidence of UTI. Behavioural
      modification or biofeedback training was not used in any patient. RESULTS: Of the
      23 patients, 13 presented with both UTI and urinary incontinence, five with
      incontinence only, four with UTI only, one with frequency and no incontinence,
      and one with haematuria. Associated symptoms included frequency/urgency,
      constipation or soiling, and straining to void or incomplete emptying (in nine
      each), and infrequent voiding in six. CIC was performed within 2 days by 15
      patients, while four others required up to 2 weeks to master CIC. However, three
      of the four patients (all older girls) who needed 2 weeks to learn the technique
      did not tolerate CIC and discontinued it within 3 weeks. Four other adolescents
      (three girls and one boy) refused to learn CIC. Of the 16 patients remaining on
      CIC only three had cystitis; no patient had a febrile UTI. Once successfully
      instituted, all patients became continent while on CIC. Six boys (mean follow-up
      4 months) had a marked decrease in their PVR. CIC was discontinued in three girls
      who voided normally to emptiness within 6 months of starting CIC; they remained
      dry and infection-free 16 months (two) and 6 years later. CONCLUSION: CIC is a
      viable therapeutic option for the treatment of dysfunctional voiding, associated
      with a large PVR, in the absence of any neurological abnormality. CIC is well
      tolerated in the sensate patient and provides a means for expeditiously achieving
      continence and improving bladder emptying cost-effectively.

PMID- 12010242
TI  - A long-term follow-up of autoaugmentation in myelodysplastic children.
AB  - OBJECTIVE: To evaluate the long-term results of patients who underwent bladder
      autoaugmentation (BA) in whom BA was used to treat a neuropathic bladder
      secondary to myelomeningocele, and who presented with a high-pressure/poorly
      compliant bladder. PATIENTS AND METHODS: Eleven patients (eight girls and three
      boys, mean age 12.8 years, mean follow-up 6.6 years) were selected who had
      undergone BA between June 1991 and June 1994. At surgery, the patients had a
      poorly compliant bladder with a mean leak point volume (LPV) of 94 mL and a mean
      leak point pressure (LPP) of 58 cmH2O. None of the patients had vesico-ureteric
      reflux (VUR) at BA; five with grade III or IV VUR had undergone endoscopic
      correction in a day-surgery procedure using a suburethral collagen injection 1-3
      weeks before BA. The patients were evaluated using clinical, urodynamic,
      radiological and endoscopic assessments. The LPV, LPP and safe bladder capacity
      (SBC, the cystometric volume at an intravesical pressure of 40 cmH2O) were
      recorded. RESULTS: At 1 year after surgery the mean LPV was 297 mL; none of the
      patients had VUR. The most recent mean LPV was 198 mL and the SBC 167 mL. The
      mean LPP remained stable at 60 cmH2O. At the last follow-up four patients had
      recurrent uni- or bilateral grade III-V VUR. At endoscopy the 'augmented' bladder
      portion had a smooth surface, compared with the grossly trabeculated lower half.
      From this finding all patients on clean intermittent catheterization were treated
      with oral oxybutynin. Some patients reported slightly less abdominal pain at
      maximum bladder volume; four needed pads to treat intermittent incontinence. On
      voiding cysto-urethrography, one patient had an hourglass-shaped bladder. Five
      patients recently underwent ileocystoplasty because of recurrent urinary tract
      infection, high-grade VUR and incontinence. CONCLUSION: These results do not
      justify the routine use of BA in hypertonic/poorly compliant bladders secondary
      to myelomeningocele. The mean follow-up of 6.6 years showed that this procedure
      failed in seven of 11 patients. Further studies might be able to identify
      subgroups in which this approach may be more appropriate.

PMID- 12010243
TI  - Detrusor myotomy: a 5-year review in unstable and non-compliant bladders.
AB  - OBJECTIVE: To identify urodynamic factors that might determine the clinical
      outcome of detrusor myotomy in incontinent children. PATIENTS AND METHODS: Six
      girls and three boys (aged 5-14 years) underwent detrusor myotomy for severe
      urinary incontinence. Seven children had spina bifida, one had traumatic
      paraplegia and one had low bladder compliance. The patients were followed for a
      minimum of 5 years. RESULTS: Urodynamic studies before surgery showed that three
      patients had normal compliance with grossly unstable detrusor contractions, and
      six had low bladder compliance with few phasic detrusor contractions. Detrusor
      leak-point pressures were > 40 cmH2O in five patients and < 40 cmH2O in four.
      Only two patients, both with grossly unstable detrusor contractions and leak
      point pressures of > 40 cmH2O, had a successful 5-year outcome. The other seven
      patients remained incontinent; six underwent further surgery and one died from
      unrelated causes. CONCLUSION: Detrusor myotomy appears to have the best outcome
      in those patients with marked phasic unstable detrusor contractions with a
      competent urethral sphincter. In this group it may have distinct advantages over
      more commonly used procedures.

PMID- 12010244
TI  - Blunt renal trauma in children with previously undiagnosed pre-existing renal
      lesions and guidelines for effective initial management of kidney injury.
AB  - OBJECTIVES: To record pre-existing renal lesions (PERL) found incidentally during
      evaluation for blunt renal trauma in children, determine their importance,
      suggest guidelines for the effective initial management of children with
      significant renal trauma and to evaluate the role of temporary percutaneous
      nephrostomy tube drainage (TPND) in these patients. PATIENTS AND METHODS: We
      reviewed 338 children who were hospitalized with blunt abdominal trauma between
      1992 and 2000. Thirty-one patients had significant renal injury, 17 before 1997
      (reviewed retrospectively) and the others reviewed and followed prospectively.
      RESULTS: Eleven of the 31 children had a PERL, which had been undiagnosed before
      the injury. The mean (range) follow-up was 52 (15-104) months. There were 22 boys
      and nine girls (mean age 9.1 years, range 2-13). The mean age was lower in
      patients with a PERL than in children with isolated renal injury. The most common
      cause of blunt renal injuries was a fall (45%) followed by motor vehicle
      accidents. Renal stones were present in five children, pelvi-ureteric junction
      obstruction in four, megaureter in one and a renal cyst in one. The mean injury
      severity scores were 12 in the children with a PERL and 14 in patients without.
      TPND was used in seven (22%) children; four were associated with a PERL. The mean
      grade of injury score for the kidney was higher in patients with a PERL and in
      children who underwent TPND than in patients who previously had a normal kidney
      and in children who did not undergo TPND. Early surgical intervention was
      required in three children; all were associated with a PERL. Of the 13 children
      who underwent surgery 11 had previous disease. CONCLUSIONS: The frequency of PERL
      is high (36%) in children with blunt renal trauma. PERL can predispose minor
      trauma to cause kidney injury even with no evidence of hydronephrosis. When a
      minor trauma results in renal injury, it is important to seek a PERL. In selected
      patients, TPND may decrease the length of hospital stay and improve the outcome
      of the injured kidney, thereby decreasing the need for further surgery in those
      with isolated renal injury; however, it appears not to decrease the need for
      later operations in children with a PERL.

PMID- 12010245
TI  - Influence of nitric oxide signalling pathways on pre-contracted human detrusor
      smooth muscle in vitro.
AB  - OBJECTIVES: To assess the effects of nitric oxide (NO) donors on human detrusor
      strips in vitro under conditions which attempt to mimic those occurring in vivo
      during the tonic phase of bladder contraction, as NO may promote relaxation by
      modulating parasympathetic excitation contraction coupling. MATERIALS AND
      METHODS: With ethical approval from the local ethics committee, human detrusor
      tissue was obtained from a heterogeneous clinical group after obtaining informed
      consent. Detrusor strips were dissected and mounted in a 1-mL, superfused organ
      bath. After pre-contraction with carbachol, the effect of NO donors, sodium
      nitroprusside (SNP) and S-nitro-N-acetylpenicillamine, a cell-permeable cyclic
      nucleotide analogue (dibutyl-cGMP), and inhibitors (methylene blue and ibuprofen)
      on isometric tension were assessed. All drugs were dissolved in Tyrode solution
      (pH 7.4), passed through a thermostatically controlled (36 degrees C) warming
      jacket and bubbled with 95% O2/5% CO2. RESULTS: Both NO donors and db-cGMP evoked
      a complex response in pre-contracted tissue, i.e. relaxation, contraction or a
      transient relaxation followed by contraction. Inhibition of soluble guanylyl
      cyclase significantly attenuated NO-mediated contraction, indicating the
      involvement of cGMP, but this inhibition did not significantly affect the
      relaxant response. The relaxant response was also potentiated by ibuprofen. SNP
      and db-cGMP evoked similar responses, although the occurrence of the responses
      (relaxation, contraction or biphasic) was significantly different in normal and
      pathological human detrusor. CONCLUSIONS: NO donors and db-cGMP modulate
      carbachol-evoked contraction of human detrusor smooth muscle in vitro. There is
      probably a NO/cGMP signalling pathway, with inhibition of endogenous cGMP by
      methylene blue, suggesting that SNP evokes contraction via cGMP. However, NO
      donors and db-cGMP evoked a complex response (relaxant, contractile or biphasic),
      suggesting that NO and cGMP may also act independently and/or via several
      pathways.

PMID- 12010246
TI  - Polyphenols in red wine inhibit the proliferation and induce apoptosis of LNCaP
      cells.
AB  - OBJECTIVE: To assess the effect of five polyphenol constituents of red wine
      (quercetin, morin, rutin, gallic acid and tannic acid) on the proliferation of
      LNCaP cells, and to quantify the extent of apoptosis with each polyphenol.
      MATERIALS AND METHODS: LNCaP cells (500) were cultured in microtitre plates and
      treated with gallic acid, tannic acid, quercetin (1, 5 and 10 micromol/L), rutin
      and morin (25, 50 and 75 micromol/L). A colorimetric immunoassay was then used to
      determine the extent of proliferation at 24, 48, 72 and 96 h, and a cell-death
      detection assay to assess apoptosis at 24, 48 and 72 h. RESULTS: Gallic and
      tannic acid (5 and 10 micromol/L), morin (50 and 75 micromol/L), quercetin (5 and
      10 micromol/L) and rutin (50 and 75 micromol/L) all significantly inhibited
      (P<0.05) cell proliferation compared with the control. Apoptotic indexes were
      significantly greater (P<0.01) in the presence of gallic (5 and 10 micromol/L)
      and tannic acid (5 and 10 micromol/L), and rutin (75 micromol/L, P<0.05) than in
      the control. The apoptotic effect of morin (75 micromol/L), although significant
      (P<0.01), only appeared at 72 h. Conversely, while significant (P<0.05) quercetin
      (5 and 10 micromol/L) had a transient (first 48 h) apoptotic effect compared with
      the control. CONCLUSION: Quercetin, rutin, morin, gallic acid and tannic acid
      inhibited the growth of LNCaP cells at different concentrations, and induced
      apoptosis. The results provide a strong rationale for studying the in vivo
      effects of these compounds.

PMID- 12010247
TI  - Intracavernosal injection of vascular endothelial growth factor induces nitric
      oxide synthase isoforms.
AB  - OBJECTIVE: To identify genes that are affected by vascular endothelial growth
      factor (VEGF), as an intracavernosal injection with VEGF improved the recovery of
      erectile function in a rat model of arteriogenic impotence, specifically
      examining the three nitric oxide synthase (NOS) genes, nNOS, eNOS, and iNOS.
      MATERIALS AND METHODS: Male rats had their pudendal arteries ligated or underwent
      a sham operation. They were then treated by an intracavernosal injection with 4
      microg of VEGF in phosphate-buffered saline (PBS) or PBS alone. At 6 and 24 h
      after treatment electrostimulation was applied to the cavernosal nerve and the
      intracorporal pressure measured. The erectile tissue was then harvested for RNA
      isolation and cryo-sectioning. The isolated RNA was used for microarray and
      reverse transcription-polymerase chain reaction (RT-PCR) analyses, and the tissue
      sections for immunohistochemical analysis. RESULTS: Microarray analysis detected
      nNOS, eNOS and iNOS at very low expression levels in PBS-treated rats; expression
      levels were higher for eNOS and iNOS in all VEGF-treated rats. These results were
      further confirmed by RT-PCR analysis. Immunohistochemical analysis identified the
      cavernosal endothelium and smooth muscle as the tissue types where eNOS and iNOS
      were up-regulated, respectively. CONCLUSIONS: This is the first report of the
      induction of both eNOS and iNOS in the penis after intracavernosal VEGF. These
      events may help support a significant recovery of erectile function after
      interrupting the blood supply to the penis.

PMID- 12010248
TI  - Effects of the chronic use of finasteride on testicular weight and
      spermatogenesis in Wistar rats.
AB  - OBJECTIVE: To evaluate spermatogenesis in rats chronically exposed to
      finasteride, as the recent use of finasteride in young men to prevent hair loss
      has raised concerns about chronic use and fertility. MATERIALS AND METHODS: Male
      Wistar rats (4 months old) were selected and divided into two groups. Group 1 (17
      rats) received a finasteride suspension of 2 mg/kg/day in saline solution, 5
      days/week for 10 months; group 2 (eight rats of the same age) were treated with
      placebo for the same period. At the end of the exposure the testes were weighed
      and processed for histological analysis. Spermatogenesis was evaluated as the
      mean number of seminiferous tubules with and without spermatozoids in their
      lumen, in five random fields on the same slide. Student's t-test was used to
      assess differences in the groups. RESULTS: In group 1, the mean (sd) weight of
      the testes was 1.55 (0.29) g and in group 2 1.58 (0.34) g (P>0.05). The
      histological analysis showed a mean of 13.35 (1.66) seminiferous tubules per
      field and 1.20 (3.30) tubules with no spermatozoids in group 1; in group 2 the
      respective values were 13.53 (1.46) and 0.06 (0.14) (P>0.05). CONCLUSION:
      Finasteride had no detectable effects on the quantitative and qualitative
      analysis of spermatogenesis in rats.

PMID- 12010249
TI  - Retroperitoneoscopic tubeless cutaneous ureterostomy.

PMID- 12010250
TI  - Right acute hemiscrotum caused by insertion of an inflamed appendix.

PMID- 12010251
TI  - Accidental resection of bilateral ureteric orifices in a patient with
      ureterosigomoidostomy.

PMID- 12010252
TI  - Increased patient satisfaction from transrectal ultrasonography and biopsy under
      sedation.

PMID- 12010254
TI  - Prostatectomy and bladder stones.

PMID- 12010255
TI  - Expert fees outstrip inflation.

PMID- 12010256
TI  - Bladder regeneration by tissue engineering.

PMID- 12010264
TI  - Anaemia and red cell transfusion in the critically ill.

PMID- 12010265
TI  - Blood component use in critically ill patients.
AB  - This prospective observational study was conducted to assess the current
      transfusion practice in critically ill patients. One thousand two hundred and
      forty-seven consecutive critically ill patients admitted between February 1999
      and October 1999 were included in the study. Overall 666 (53%) patients were
      administered red cells. Transfused patients had significantly higher intensive
      care unit mortality but also had higher Acute Physiology and Chronic Health
      Evaluation II scores and longer durations of stay. The average pretransfusion
      haemoglobin concentration was < 9 g.dl(-1) in 75% of transfusion episodes. The
      common indications for transfusion were low haemoglobin (72%) and haemorrhage
      (25%). Overall, 202 (16%) and 281 (22%) of the patients were transfused platelets
      and fresh frozen plasma, respectively. The indications for transfusion were
      haemorrhage, low platelet counts, prolonged prothrombin time or to provide cover
      for invasive interventions. Most platelet transfusions were given at values in
      the order of 50-100 x 10(9).l(-1). The pretransfusion platelet count varied
      according to the indications for transfusion. This study showed that transfusion
      practice is consistent and that in general there does not seem to be an excessive
      use of blood components in critically ill patients.

PMID- 12010266
TI  - The influence of timing and route of administration of intravenous ketorolac on
      analgesia after hand surgery.
AB  - A double-blind clinical trial was conducted on 47 patients scheduled for hand
      surgery under general anaesthesia to determine whether ketorolac given as part of
      an intravenous regional anaesthesia technique could provide better postoperative
      analgesia than ketorolac given intravenously either before or after surgery.
      Patients were randomly allocated to one of three groups to receive ketorolac 20
      mg: intravenously in the non-operative arm before surgery (systemic presurgery
      group); intravenously to the operative arm after tourniquet inflation (regional
      presurgery group); intravenously in the non-operative arm after surgery (systemic
      postsurgery group). Postoperative pain scores were similar in the systemic
      presurgery and regional presurgery groups. The mean visual analogue summary pain
      score during the 24 h after surgery was 12.2 mm higher in the systemic
      postsurgery group than in the systemic presurgery group (95% CI: 0.8-23.7 mm, p =
      0.037). There were no clinically important differences in mean postoperative
      visual analogue pain scores between the three study groups. There were no
      statistical differences in the mean postoperative morphine requirements between
      the three study groups. There is no benefit, in terms of improved postoperative
      analgesia, in giving ketorolac as an intravenous regional anaesthetic compared
      with systemic administration before surgery. The administration of ketorolac
      after surgery, rather then before, is not supported.

PMID- 12010267
TI  - Effects of low-dose alfentanil administration on central respiratory drive and
      respiratory pattern in spontaneously breathing ASA 1 patients.
AB  - The aim of this study was to assess the short-term effects of the administration
      of low doses of alfentanil on respiratory drive and respiratory pattern. We
      studied 17 ASA I patients scheduled for minor surgery or endoscopic procedures.
      During spontaneous ventilation, Respiratory Rate, Tidal Volume, Total Respiratory
      Cycle, Inspiratory and Expiratory Time, Mean Inspiratory Flow, P0.1, S(a)O(2) and
      EtCO(2) were all measured. The inspired oxygen concentration was 21% and
      measurements were made at baseline, 5 min (T1), 10 min (T2) and 15 min (T3)
      following an intravenous bolus injection 10 microg.kg(-1) alfentanil. The
      administration of alfentanil produced a significant (p < 0.05) reduction in
      S(a)O(2), minute volume and P0.1. In ASA I spontaneously breathing patients, the
      pre-operative administration of low doses of alfentanil can initially reduce the
      respiratory centre activity leading to a reduction in minute volume and S(a)O(2).
      We therefore recommend careful monitoring of cardio-respiratory function in ASA I
      patients, following the administration of alfentanil.

PMID- 12010268
TI  - Body computed tomography in critically ill patients.
AB  - The aim of the study was to assess the effectiveness of computed tomography in
      the management of critically ill patients. We performed a prospective study over
      a 4-month period. The requesting clinician was asked to document their clinical
      diagnosis and confidence thereof on a visual analogue scale. They were also asked
      about their management plan if computed tomography had not been available. After
      imaging, any change in the management plan was assessed. During the study period,
      16 computed tomograms were performed on 14 patients. There were 21 possible
      clinical diagnoses: of these eight were confirmed, and 13 were refuted. Seven new
      diagnoses were established. Computed tomography did not help in the management of
      two patients and it led to more confusion in the management of one patient. The
      management of seven patients was altered after computed tomography and in six the
      management depended solely on computed tomography findings.

PMID- 12010269
TI  - Awareness during general anaesthesia: a review of 81 cases from the Anaesthetic
      Incident Monitoring Study.
AB  - Because of recent studies suggesting that awareness is still a major issue in
      anaesthetic practice, we reviewed 8372 incidents reported to the Anaesthetic
      Incident Monitoring Study. There were 81 cases in which peri-operative recall was
      consistent with awareness. There were 50 cases of definite awareness and 31 cases
      with a high probability of awareness. In 13 of the 81 incidents, the patients
      appeared to receive adequate doses of anaesthetic drugs. Where the cause could be
      determined, awareness was mainly due to drug error resulting in inadvertent
      paralysis of an awake patient (n = 32) and failure of delivery of volatile
      anaesthetic (n = 16). Less common causes included prolonged attempts at
      intubation of the trachea (n = 5), deliberate withdrawal of volatile anaesthetic
      (n = 4) or muscle relaxant apnoea with inadequate administration of hypnotic (n =
      3). An objective central nervous system depth of anaesthesia monitor may have
      prevented 42 of these incidents and an improved drug administration system may
      have prevented 32. On the basis of these reports, we have developed guidelines
      that may have prevented the majority of these incidents.

PMID- 12010270
TI  - Efficacy of microfiltration in decreasing propofol-induced pain.
AB  - In a randomised, double-blinded, two-centre trial we evaluated the effect of a
      microbiological filter (Supor, Pall Life Sciences) on propofol injection pain. We
      studied 336 unpremedicated adult patients, who graded pain experienced during
      induction of anaesthesia with propofol on a 4-point verbal rating scale. Use of
      the microfilter reduced both the incidence and severity of propofol injection
      pain (p < 0.001). Incidence of severe pain in the filter group was 2.4% compared
      with 16.6% in the control group. Overall, 33.7% in the filter group experienced
      pain compared with 62.1% in the control group. A microbiological filter may
      provide a non-pharmacological alternative to a lidocaine/propofol mixture for
      reducing injection pain. It would also reduce the risk of any glass and bacterial
      contamination.

PMID- 12010271
TI  - Pulmonary artery blood temperature and the measurement of cardiac output by
      thermodilution.
AB  - Thermodilution cardiac output measurement assumes that the temperature within the
      pulmonary artery is stable during the measurement period. This may not be
      achieved in clinical practice because of temperature changes that are not solely
      produced by the thermal indicator. Such temperature changes constitute thermal
      noise. Thermal noise and how it may interfere with measurement is discussed with
      reference to both the injectate and the thermal filament methods of
      thermodilution cardiac output measurement.

PMID- 12010272
TI  - Safer epidural and spinal connectors.
AB  - Inadvertent cross-connection of epidural local anaesthetic delivery systems with
      intravenous lines can cause significant morbidity and even death. Inadvertent
      intrathecal injection of toxic intravenous drugs has already led to many deaths.
      If epidural and spinal systems had the standard Luer lock connection reversed the
      problem would be prevented. The practical implications of this idea are explored.
      Patient safety would be enhanced if this system were adopted.

PMID- 12010273
TI  - Efficacy of catheter needles with safeguard mechanisms.
AB  - There has been considerable interest in using safeguarded needles to reduce
      needlestick injury. In a randomised design, we studied the efficacy and safety of
      two such needles (the Insyte AutoGuard and the Protective Acuvance), by comparing
      them with a conventional catheter needle (Insyte), for intravenous cannulation
      (18 G) in 150 patients and for intra-arterial cannulation in another 150 patients
      (20 G). For intravenous cannulation, the success rates were similar in the three
      groups but insertion of the AutoGuard or Acuvance catheter was significantly more
      difficult than the conventional catheter. For the Acuvance, the back-flow of
      blood into the chamber was sometimes too slow. For intra-arterial cannulation,
      insertion of the AutoGuard was significantly more difficult than the other two
      devices, mainly because the backflow chamber of the AutoGuard was too short so
      that the chamber often filled with blood before cannulation. Insertion of the
      Acuvance was significantly more difficult than the conventional catheter. For
      both intravenous and intra-arterial insertion, handling of the withdrawn needle
      was judged significantly safer in the AutoGuard group than the other two groups,
      whereas there was no significant difference in the safety between the Acuvance
      and conventional groups. In five subjects from the AutoGuard group, blood
      splashed on retraction of the needle. Blood contamination during needle
      withdrawal occurred frequently in the control and Acuvance groups, but rarely
      occurred in the AutoGuard group. Therefore, the AutoGuard needle is more suitable
      for intravenous cannulation, and the Acuvance is more suitable for intra-arterial
      cannulation.

PMID- 12010274
TI  - Isolated systolic hypertension.

PMID- 12010275
TI  - Predicting difficult intubation 2.

PMID- 12010276
TI  - Percutaneous tracheostomy in morbidly obese patients.

PMID- 12010277
TI  - Spontaneous pneumothorax secondary to osteosarcoma metastasis.

PMID- 12010278
TI  - Near-infrared spectroscopy.

PMID- 12010279
TI  - Unusual cause of circuit failure.

PMID- 12010280
TI  - Head-up tilt and subarachnoid block.

PMID- 12010281
TI  - A use for combined spinal epidural anaesthesia at last!

PMID- 12010282
TI  - Draining intraperitoneal gas after laparoscopy.

PMID- 12010283
TI  - Temperature measurements -- which method is best?

PMID- 12010284
TI  - Paediatric tonsillectomy and PONV -- big little problem remains big!

PMID- 12010285
TI  - The 2001 Xenia Foressellina prize.

PMID- 12010286
TI  - CT angiography in the assessment of carotid artery atherosclerosis.
AB  - OBJECTIVE: The aim of the study was to evaluate the ability of CT angiography
      (CTA) to detect atherosclerosis of the carotid arteries in comparison with 3D
      time-of-flight MR angiography (3D TOF MRA), using contrast angiography and
      intravascular ultrasound (IVUS) as a reference. MATERIAL AND METHODS: Contrast
      angiography and CTA were performed in 31 patients (mean age 65 years, range 45
      79). The image quality was evaluated, atherosclerotic lesions were registered,
      and diameter stenosis degree was visually estimated from axial source images of
      CTA and 3D TOF MRA (21 patients), and results of interpretations were compared.
      The comparison of quantitative measurements was performed using IVUS as a
      reference. RESULTS: Contrast angiography detected 51 lesions (mean diameter
      stenosis 50%, range 10-100%), and CTA detected all same lesions. CTA provided
      better image quality and consistency of image interpretation than 3D TOF MRA.
      IVUS verified 29 atherosclerotic lesions with a mean diameter stenosis of 35%,
      (range 4-40%). CTA yielded a sensitivity of 96% to 100% (< or =10% or < or =20%
      diameter stenosis regarded as normal) for the detection of lesions with reference
      to IVUS. CONCLUSION: CTA seems feasible and accurate for the detection of
      atherosclerosis in carotid arteries.

PMID- 12010287
TI  - MR imaging of pituitary adenomas treated with the prolactin inhibitor
      quinagolide.
AB  - PURPOSE: To evaluate the volume of micro- and macroadenomas in quinagolide
      treated patients with resistance to or intolerance of bromocriptine. MATERIAL AND
      METHODS: The effect of the prolactin inhibitor quinagolide on the volume of
      pituitary adenoma was evaluated retrospectively in 11 female patients. Prolactin
      levels before and after the treatment were also recorded. The indications for
      quinagolide therapy were side-effects of bromocriptine in 5 cases, a poor
      response to bromocriptine in 5 cases and both in 1 case. MR imaging with a 1.0-T
      magnet was performed to determine the volume reduction of the adenomas. RESULTS:
      The average volume reduction of macroadenomas was 324 mm3 (46%) and that of
      microadenomas 73 mm3 (57%). The level of prolactin secreted by macroadenomas was
      reduced by an average of 163 microg/l (65%) and that by microadenomas of 113
      microg (73%). In 2 microadenomas and in 1 macroadenoma, signal intensity changed
      during the treatment in T1-weighted images. In follow-up no changes in signal
      intensity were seen in 8 adenomas in non-contrast T1-weighted images. A
      haemorrhagic lesion was seen in 1 macroadenoma before treatment, but it
      disappeared during treatment. CONCLUSION: Quinagolide was found to be an
      effective alternative to bromocriptine in cases with drug intolerance or
      resistance, and MR imaging a suitable method for the follow-up of macro- and
      microadenomas.

PMID- 12010289
TI  - US-guided fine-needle aspiration biopsy of thyroid nodules.
AB  - PURPOSE: To determine which nodular areas provide most adequate and accurate
      material for cytology during US-guided fine-needle aspiration biopsy (FNAB) of
      thyroid nodules. MATERIAL AND METHODS: In a prospective multicentre study, US
      guided FNAB (0.8 mm) was performed in 342 thyroid nodules (338 patients, 285
      women, 18-83 years, 285 palpable). Histology was obtained in 169 nodules,
      revealing 75 neoplasms (44.4%) including 18 cancers (10.7%). In 206 solid
      nodules, 2 passes (central and peripheral) were compared. In 82 complex nodules,
      2 passes (solid area and cystic area) were compared. RESULTS: The inadequacy rate
      was 16.4% and the false-negative rates were 2.2% and 28.1% for the diagnosis of
      cancer and neoplasm, respectively. In solid nodules, material was more adequate
      with peripheral passes compared to central passes, but the difference was not
      significant. In complex nodules, the inadequacy rate was much higher for passes
      in cystic areas (80.5%) compared to passes in solid areas (46.3%). CONCLUSION:
      Cystic areas due to degeneration seldom provided adequate material when
      aspirated. Aspiration should always be obtained from solid areas, at best using
      US-guidance. Adenomas and non-neoplastic nodules were difficult to distinguish.

PMID- 12010290
TI  - MR of a nasal glioma in a young infant.
AB  - We describe MR findings of a nasal glioma in a 5-week-old male infant with
      feeding difficulties and symptoms of respiratory distress. Endoscopic examination
      revealed a soft tissue mass in the nasal cavity. In T1- and T2-weighted images,
      the gyral structure of grey matter was visible. In T1-weighted images, a tissue
      component with a lower signal intensity equal to that of white matter was also
      well distinguishable. Edge enhancement of the tumour was due to the nasal mucosal
      epithelium covering the tumour. MR images were useful to rule out intracranial
      extension of the nasal cavity lesion and the brain, thus excluding the diagnosis
      of encephalocele. The lesion was excised and histologically characterized as
      heterotopic brain tissue.

PMID- 12010291
TI  - Ectopic thymic tissue in the paediatric age group.
AB  - PURPOSE: The presence of ectopic thymic tissue is well known along the
      embryological descent track in the neck. The aim of this study was to detect the
      frequency of cervical thymic rests in children. MATERIAL AND METHODS: Eighteen
      consecutive children had neck US performed using an ATL 5000 unit with a 12.5 MHz
      liner probe. The presence of small rests of thymic tissue was sought. RESULTS:
      61% of the children had thymic tissue detected in the neck. Out of those with
      positive findings, 82% had a thymic rest on the right side, 9% on the left side
      and 9% had thymic rests bilaterally. CONCLUSION: Small rests of ectopic thymic
      tissue in the cervical region are commonly seen in the paediatric age group. It
      is important to identify the thymic rests for what they are and avoid unnecessary
      anxiety or intervention.

PMID- 12010292
TI  - Early postoperative tissue harmonic sonography of the thyroid gland.
AB  - PURPOSE: Fundamental gray-scale imaging (FGI) is known to be unuseful for thyroid
      imaging in the early postoperative setting. Thus, we evaluated the feasability of
      tissue harmonic imaging (THI) early after thyroid resection. MATERIAL AND
      METHODS: FGI and THI of the neck were performed in 48 consecutive patients 4 days
      after surgery. The examiner was blinded to patient diagnoses and types of
      surgery. FGI and THI examinations were stored on videotape and reviewed offline
      by two different readers who rated the quality of delineation of the organ
      borders and presence or absence of focal lesions. The results were compared to
      neck US performed 12 weeks after surgery. RESULTS: Delineation of the thyroid
      remnants in THI/FGI was rated to be excellent in 22/2, good in 11/9, poor in 3/16
      and not visible at all in 4/13 patients. The correlation between THI-volumetry
      and control-volumetry was very high (r=0.81; p<0.0001). THI but not FGI depicted
      presence or absence of solid thyroid nodules with 100% accuracy. CONCLUSION: THI
      is a feasible method for thyroid US in the early postoperative setting. It
      permits volumetry of the residual thyroid tissue and accurately depicts nodules
      within the thyroid remnant.

PMID- 12010294
TI  - Ultrasound-guided percutaneous thoracoabdominal biopsy.
AB  - This review will discuss the benefits and disadvantages of ultrasound-guided
      percutaneous fine-needle aspiration and cutting needle biopsies. Clinical
      efficacy, cost-effectiveness, some controversies and safety will be reviewed.

PMID- 12010295
TI  - HRCT findings in the lungs of primary care patients with lower respiratory tract
      infection.
AB  - PURPOSE: To survey the prevalence and type of lung patterns detectable at high
      resolution CT (HRCT) in a primary care population seeking help for cough and
      fever. MATERIAL AND METHODS: The HRCT patterns of 103 patients obtained at the
      primary visit to a municipal health centre for cough and fever were evaluated.
      Forced expiratory examinations were obtained in 93 patients. RESULTS: Lower
      respiratory tract infection (LRTI)-related findings (present at inclusion, healed
      at follow-up, not explained by any other factor) were seen in 19 patients
      (18.7%), of whom 11 also showed opacities, even though of lesser extent, at
      conventional chest radiography. The following patterns were found: ground-glass
      opacity (58%), discrete consolidations (52%), confluent consolidations (16%; 1
      case with an air bronchogram), air space nodules (10%), peribronchovascular
      thickening (37%), tree-in-bud pattern (26%), free pleural fluid (5%), and septal
      thickening (5%). An expiratory mosaic pattern was seen in 19 (20%) out of 93
      patients. In addition, lymph node enlargement (>1 cm) was recorded in 7 patients
      out of 103. CONCLUSION: HRCT is more sensitive than chest radiography in
      detecting LRTI-related lung lesions in a primary care population. The pattern
      typically comprises subtle scattered polymorphous opacities with varying
      attenuation affecting several lung segments. LRTI-related HRCT pattern deserves
      consideration as a differential diagnostic alternative in patients examined due
      to any lower respiratory tract symptoms.

PMID- 12010296
TI  - An unusual radiographic finding in pulmonary parenchymal endometriosis.
AB  - Thoracic endometriosis is an uncommon disorder. In most cases, the diagnosis is
      based on history alone and radiographic findings depend on the menstrual cycle.
      CT findings include ill-defined or well-defined opacities, nodular lesions,
      cavities, cystic changes and bullous formation. We report a case of pulmonary
      parenchymal endometriosis with an unusual radiographic finding.

PMID- 12010297
TI  - Lateral thoracic artery embolization in cystic fibrosis.
AB  - We report the embolization of an aberrant origin of haemoptysis - from the
      internal branch of the lateral thoracic artery - in a patient affected by cystic
      fibrosis. The technical implications for embolotheraphy in case of an aberrant
      origin of a haemorrhage are emphasized. Many different systemic arteries may
      contribute to the blood supply of the lung and many connections may exist between
      the systemic, bronchial and pulmonary circulations. The presence of non-bronchial
      systemic arteries supply should be investigated when inconclusive findings are
      seen during bronchial artery embolization for haemoptysis.

PMID- 12010298
TI  - Continuous ambulatory peritoneal dialysis.
AB  - PURPOSE: To assess complications of continuous ambulatory peritoneal dialysis
      (CAPD) in uremic patients with and without clinical symptoms by CT
      peritoneography. MATERIAL AND METHODS: A total of 64 patients with end-stage
      renal disease and on continuous CAPD were investigated. Twenty-eight had some
      clinical symptoms, which might be related to the complications of CAPD. Thirty
      six patients had no complaints or symptoms due to the dialysis treatment.
      RESULTS: CT peritoneography revealed various complications including hernias
      (50%), dialysate leakage (46%), localized fluid collection (4%) and peritoneal
      adhesions (4%) in the patients who had clinical symptoms that might be related to
      the dialysis treatment. Moreover, similar complications were found in the
      asymptomatic patients at a lower rate: hernia (3%), dialysate leakage (17%),
      peritoneal adhesions (3%) and abdominal wall laxity (3%). Complication detection
      rate by CT peritoneography was 68% (n=19) in the symptomatic patients and 22%
      (n=8) in the asymptomatic patients. The number of complications found in each
      group was significant. CONCLUSION: CT peritoneography was an effective modality
      in detecting complications from CAPD in patients with and without clinical
      symptoms.

PMID- 12010299
TI  - MR characteristics of acute cholangitis.
AB  - PURPOSE: To describe the MR appearance of acute cholangitis and discuss the role
      of MR imaging as a diagnostic method in this disease. MATERIAL AND METHODS: Of 60
      patients with clinical acute cholangitis, 12 were examined with MR before
      endoscopic retrograde pancreatography (ERCP). A retrospective review was
      performed of MR and ERCP findings. The MR findings registered were presence of
      biliary duct dilatation, intraluminal filling defects due to stones or sludge,
      bands of mucosal oedema of the biliary ducts, intra- and retroperitoneal
      oedema/fluid, and definition of the cause of obstruction, e.g. stones, stenosis
      or tumour was made. RESULTS: Acute cholangitis was related to obstruction from
      choledocholithiasis (n=8), pancreatic cancer (n=1), benign biliary duct stricture
      (n=1), papillary stenosis (n=1) and without evidence of an obstructing cause
      (n=1). One patient had an acute obstructive suppurative (toxic) cholangitis.
      CONCLUSION: MR imaging has a role in the non-invasive radiographic arsenal of
      techniques to confirm or exclude the diagnosis of acute cholangitis, especially
      in older patients where the clinical symptoms may be vague.

PMID- 12010300
TI  - Efficacy of sequential use of superparamagnetic iron oxide and gadolinium in
      liver MR imaging.
AB  - PURPOSE: To evaluate the efficacy of combined (double contrast) use of
      superparamagnetic iron particles (SPIOs) and gadolinium (Gd) in liver MR imaging.
      MATERIAL AND METHODS: Unenhanced, Gd-enhanced, SPIO-enhanced, and both SPIO- and
      Gd-enhanced images were acquired at 1.5 T. Twenty patients with previously
      detected liver lesions were included. Fast SE-STIR, and breath-hold true FISP,
      fat-suppressed T1- and T2-weighted sequences were obtained with all techniques.
      Lesion count was assessed by consensus reading. RESULTS: Collective evaluation of
      all MR sequences revealed 61 lesions in 16 patients; SPIO-enhanced MR detected
      lesions with a sensitivity of 95% (n=58). The sensitivity of unenhanced MR
      imaging was 90% (n=55). There was no statistical difference between SPIO-enhanced
      and unenhanced MR images. From single sequences, the greatest number of lesions
      was detected with the SPIO-enhanced fast SE-STIR sequence (n=56, sensitivity
      92%). By using the fat-suppressed T1-weighted sequence, Gd-enhanced and both SPIO
      and Gd-enhanced MR images demonstrated sensitivities of 77% (n=47) and 80%
      (n=49), respectively. Despite the combined use of both contrast media, this
      sequence was significantly less sensitive in lesion detection when compared to
      SPIO-enhanced imaging. CONCLUSION: SPIO-enhanced MR imaging was the most
      sensitive method in lesion detection. The benefit of the combined use of SPIO and
      Gd was negligible.

PMID- 12010301
TI  - A new liquid embolic material for liver tumors.
AB  - PURPOSE: To evaluate the feasibility of a new liquid embolic material, Onyx, for
      treating liver tumors. MATERIAL AND METHODS: Onyx is a mixture of 6% (w/v)
      ethylene-vinyl-alcohol copolymer dissolved in anhydrous dimethyl sulfoxide (DMSO)
      with 28% (w/v) tantalum powder. In addition to 6% Onyx, we also tried 4%, 2% and
      1% solutions, prepared by adjusting the amount of DMSO. We used 15 white rabbits
      with liver tumors created by percutaneous injection of VX2 tumor cells. In 4
      groups with 3 rabbits in each, the liver arteries were embolized with 6%, 4%, 2%
      and 1% Onyx, respectively, and in 3 rabbits DMSO alone was injected. The
      injections were performed just proximal to the bifurcation of the proper hepatic
      artery, followed by celiac arteriography. Post mortem, the livers were examined
      by soft-tissue radiography, and liver-tissue section microscopy. RESULTS: The
      maximum number of arterial branching points passed by embolic material in either
      the right or left hepatic arteries was 11, 15 and 16, for 6%, 4% and 2% Onyx,
      respectively, but was non-measurable for 1% Onyx. Minimum diameters of arteries
      reached by 6%, 4%, 2% and 1% Onyx in tumorous areas were 40 microm, 35 microm, 20
      microm and 10 microm, respectively, and in non-tumorous areas 35 microm, 5
      microm, 5 microm and 5 microm, respectively. CONCLUSION: This study suggests that
      Onyx may be feasible for treatment of hepatic tumors.

PMID- 12010302
TI  - Relapsing hydatid disease involving the vertebral body and paravertebral soft
      tissues.
AB  - Hydatid disease involving the vertebral body and paravertebral soft tissues is
      rare even in rural areas where echinococcosis is endemic. We report a case with
      hydatid disease in the T11-L1 vertebral bodies and involvement in bilateral psoas
      muscles.

PMID- 12010303
TI  - Peritoneal calcifications in a patient on continuous ambulatory peritoneal
      dialysis.
AB  - Complications in a long-term ambulatory peritoneal dialysis patient are
      described.

PMID- 12010304
TI  - Jejunojejunal intussusception secondary to lipoma in an adult.
AB  - Lipoma is a rare cause of adult intussusception. We present the CT findings of an
      adult patient with jejunojejunal intussusception secondary to submucosal lipoma
      as the lead point in this case report.

PMID- 12010305
TI  - Dynamic contrast-enhanced mr imaging and histopathology in chronic achilles
      tendinosis. A longitudinal MR study of 15 patients.
AB  - PURPOSE: To evaluate the value of dynamic contrast-enhanced MR imaging (DEMRI)
      and its correlation to symptoms and histopathology in chronic Achilles
      tendinosis. MATERIAL AND METHODS: Fifteen patients with severe symptoms underwent
      DEMRI preoperatively and 2 years postoperatively. US-guided core biopsies of
      tendinosis tissue were obtained preoperatively and the specimens were analyzed
      using a semiquantitative protocol. DEMRI was evaluated by calculating the area
      under curve (AUC) of signal alteration and the static MR by a semiquantitative
      grading scale. A questionnaire and clinical examination evaluated the clinical
      outcome. RESULTS: Early contrast enhancement (first 72 s) was seen in DEMRI at
      tendon lesions of the symptomatic Achilles tendons with a significant difference
      to asymptomatic contralateral tendon that revealed no or mild enhancement.
      Increased severity of tendon pathology (including fiber structure abnormality,
      increased vascularity, rounding of nuclei and increased amount of
      glycosaminoglycans) was correlated to both dynamic and static signal enhancement.
      Two years following surgical treatment, the signal alterations showed regression
      of early contrast enhancement (AUC decreased from 9 preoperatively to 2
      postoperatively). The clinical outcome was as follows: 8 patients excellent, 4
      good, 2 fair and 1 poor. CONCLUSION: Patients with chronic painful achillodynia
      showed an early contrast-agent enhancement corresponding to the tendon lesion.
      Increased enhancement correlated to increased severity of tendon histopathology
      and patient symptoms. Two years after surgical treatment the contrast-agent
      enhancement decreased.

PMID- 12010306
TI  - MR imaging, bone scintigraphy, and radiography in bone stress injuries of the
      pelvis and the lower extremity.
AB  - PURPOSE: To compare MR imaging, radiography and bone scintigraphy in the
      diagnosis of stress injuries to bones of the pelvis and lower extremity. MATERIAL
      AND METHODS: Fifty consecutive conscripts with clinical signs of a stress injury
      to bone underwent MR imaging and bone scintigraphy. Forty-three patients also had
      radiographs available. Bone scintigraphy served as a gold standard. RESULTS:
      Compared to the bone scintigraphy, the sensitivity of radiography was 56%,
      specificity 94%, accuracy 67%, positive predictive value (PPV) 95%, and negative
      predictive value (NPV) 48%. The kappa value for radiography and bone scintigraphy
      was fair (0.39). Correspondingly, the sensitivity of MR imaging was 100%,
      specificity 86%, accuracy 95%, PPV 93% and NPV 100%. The kappa value for MR
      imaging and bone scintigraphy was very good (0.89). MR imaging depicted 3 bone
      stress injuries that were not visible on bone scintigraphy. Positive findings
      obtained from radiography correlated with MR signs of fracture line or callus
      (p<0.001). CONCLUSION: MR imaging is more sensitive than two-phase bone
      scintigraphy, and MR imaging should be used as the gold standard in the
      assessment of stress injuries of bone. Radiography reveals mainly the late phases
      of bone stress injuries, such as stress fracture and callus.

PMID- 12010307
TI  - Capsular distance in the hip of the healthy child - normal values with sonography
      and MR imaging.
AB  - PURPOSE: To determine the normal values of the anterior and posterior capsular
      distances of the hip joint in healthy children by means of US, using MR imaging
      as reference, and to evaluate any possible correlation between age, length,
      weight and anterior capsular distance (ACD). MATERIAL AND METHODS: In our first
      study both hips in 14 healthy children (5-18 years old) were examined with US and
      MR to obtain measurements of the ACD and the posterior capsular distance (PCD).
      The distance from the anterior or posterior aspect of the femoral neck to the
      anterior or posterior aspect, respectively, of the outer limit of the capsule was
      determined. The distances were measured both with the hips in spontaneous
      external rotation of 10-15 degrees and in internal rotation of 45 degrees. In our
      second study, both hips in 28 healthy children (3-16 years old) were examined
      with US to determine the ACD. Age, length and weight were recorded. RESULTS:
      Study I: There was good correlation between the US and MR measurements in all
      positions. The ACD measured by US was significantly increased in inward rotation
      of the hip. Study II: There was no correlation between ACD and age, length or
      weight. CONCLUSION: The PCD of the hip joint can be accurately measured by US
      with the hip in internal rotation of 45 degrees. When compared with MR values,
      the ACD measured by US was dependent on the degree of rotation of the leg and
      increased significantly in internal rotation. Because the outer limit of the
      external layer of the joint capsule is sonographically more distinct, we suggest
      that the capsular distance should be measured from the outer limit of the joint
      capsule to the anterior or posterior aspect of the femoral neck. The measurement
      should be made perpendicular to the femoral neck, at the position where the
      greatest numerical value is obtained.

PMID- 12010308
TI  - Gray-scale and Doppler ultrasound imaging features of vascular canals in human
      femoral condylar epiphysis.
AB  - PURPOSE: To describe the gray-scale and color Doppler ultrasound imaging features
      of vascular canals in human femoral condylar epiphysis. MATERIAL AND METHODS:
      Vascular canals in the femoral condylar epiphysis were examined using gray-scale
      and Doppler US. The study was performed in 45 volunteers (aged <1 month-72 years)
      who comprised 1 subject with short stature, 1 subject with Klippel-Trenaunay
      Weber syndrome and 43 subjects with normal growth. RESULTS: In the 8-year-old and
      younger group (n=34), vascular canals were observed in 32 subjects (94%), whereas
      vascular canals were not observed in the 9-year-old and older group (n=11).
      Vascular canals were visualized as hyperechoic lines and dots. With Doppler US,
      blood flow in the vascular canals was observed in 20 of the 32 subjects (62.5%).
      Spectral Doppler analysis was possible in 15 subjects, in all of whom only
      arterial waveforms were observed. CONCLUSION: US was helpful to delineate the
      vascular canals and flow therein. The detection and evaluation of vascular canals
      and blood flow therein may prove useful in understanding growth.

PMID- 12010309
TI  - Acetabular inclination and anteversion in infants using 3D MR imaging.
AB  - PURPOSE: To establish if 3D MR imaging could be used for measurements of
      acetabular inclination and anteversion in infants specimens. MATERIAL AND
      METHODS: 3D MR data of 3 pelvic preparations of 6-week- to 10-month-old infant
      specimens was gathered. MR imaging in transaxial and frontal planes was carried
      out to measure the acetabular inclination and anteversion: a method to determine
      the MR planes for measurements is described. It was oriented on anatomical
      landmarks of the pelvis and therefore allowed adjustment of the frontal and
      transaxial planes, independent of the pelvis position. RESULTS: The mean
      acetabular inclination angle was 48 degrees, and the mean acetabular anteversion
      was 23 degrees. Because of the low number of cases the results can only be
      assessed as a tendency, but MR imaging seems to be suitable for measurements of
      acetabular inclination and anteversion.

PMID- 12010310
TI  - Behaviour of the 2.1-mm (14 G) automated biopsy needle in phantoms.
AB  - PURPOSE: To study the behaviour of the 2.1-mm (14 G) core biopsy needle in
      targets of different consistencies and to correlate the needle behaviour to
      lengths of the samples. MATERIAL AND METHODS: A series of butter blocks at
      temperatures of -5 degrees C, -2 degrees C, +1 degrees C, +4 degrees C, +7
      degrees C, +10 degrees C, +13 degrees C, +16 degrees C and +19 degrees C
      simulating lesions of different hardness in human breast, were passed with
      needles (3 passes at each temperature). Inner needle behaviour was studied both
      with and without outer cannula effect. RESULTS: At +4 degrees C to +13 degrees C
      the needle had a curved course, deviated to the side of its tip. At +4 degrees C,
      the needle was most deviated (range 4, 8, 10 degrees ) and the samples were
      largest (8, 12, 12 mm). At -5 degrees C to +1 degrees C the needle was bent, the
      cannula was not triggered and no sample was obtained. At +16 degrees C and +19
      degrees C the needle had a straight course and the length of the sample was
      decreasing. CONCLUSION: Behaviour of the inner needle as well as the cannula
      depends on the hardness of the target. Targets of intermediate hardness yield
      adequate samples when the inner needle takes a curved course deviated toward the
      tip and get restored by the cannula.

PMID- 12010311
TI  - Image-guided fine-needle aspiration cytology of deep-seated enlarged lymph nodes.
AB  - PURPOSE: To evaluate the role of image-guided fine-needle aspiration cytology
      (FNAC) of deep-seated lymph nodes. MATERIAL AND METHODS: Image-guided FNACs were
      performed on 242 patients of deep-seated lymph nodes which included thoracic,
      retroperitoneal and abdominal nodes. A sterile 3.5/5-MHz micro convex sector
      probe was used for localisation of the node. The FNAC was performed using a 0.7-
      to 0.9-mm needle with the stylet removed and attached to a 20-ml syringe and FNAC
      handle after the needle was visualised in the lesion. For each case a minimum of
      4-5 smears were made, and two observers without bias interpreted the smears.
      RESULTS: A total of 242 patients were aspirated, of which 216 (90%) aspirations
      were US-guided and the remaining 26 (10%) were CT-guided. Adequate material for
      cytologic diagnosis was obtained in 208 (86%) patients with a similar diagnostic
      accuracy. The aspirate material was non-representative or scanty in 34 (14%)
      patients. The most common cytological diagnosis was tuberculosis/consistent with
      tuberculosis seen in 108 (45%) patients followed by metastasis (17%) and reactive
      hyperplasia (10%). Non-Hodgkin lymphoma was diagnosed in 22 (9%) patients. All
      patients were briefly followed for a period of 1 1/2 to 2 years (mean 1 year).
      CONCLUSION: Image-guided FNAC has a pivotal role, and is a cost-effective tool
      for establishing tissue diagnosis as a primary investigative modality. It is also
      helpful and accurate in follow-up of patients with a known malignant disease,
      thereby avoiding surgical intervention.

PMID- 12010312
TI  - Electron microscopic study to compare preclinical Cushing's syndrome with overt
      Cushing's syndrome.
AB  - BACKGROUND: No significant differences in gross and light- microscopic features
      have been reported between preclinical and overt Cushing's adenomas. In this
      study, the ultrastructural differences between the two syndromes was attempted to
      be clarified. METHODS: Two preclinical Cushing's syndrome adenomas and two overt
      Cushing's syndrome adenomas obtained from surgical extirpation were examined in
      an electron microscopic study. RESULTS: Light microscopically, the adenomas of
      both syndromes were composed predominantly of clear cells, with few compact
      cells. Ultrastructurally, the prominent differences were of development in each
      organelle: the preclinical Cushing's adenomas had undeveloped mitochondria, which
      were smaller in size and had sparse cristae, lysosomes and polysomes, whereas the
      overt Cushing's adenomas contained well-developed mitochondria which were larger
      in size and were filled with abundant cristae, smooth endoplasmic reticulum
      (SER), lysosomes and polysomes. CONCLUSIONS: Preclinical Cushing's syndrome
      adenomas were ultrastructurally characterized by a reduced number of cellular
      organelles such as mitochondria and SER, which are necessary to synthesize
      glucocorticoid hormones. However, examination of a greater number of adenomas
      will be required to be able to draw conclusions on the ultrastructural
      differences between the two syndromes.

PMID- 12010313
TI  - Continent urinary reservoir formation with transverse colon for patients with
      pelvic irradiation.
AB  - BACKGROUND: The creation of a continent transverse colon pouch for patients who
      had previously received radiation therapy for cervical cancer was attempted.
      METHODS: Three patients underwent construction of a continent urinary reservoir.
      Approximately 30 cm of a transverse colon segment was isolated for constructing a
      pouch. A reconfigured colon segment was used in two cases as a continent valve
      and the appendix was used in one case. Both ureters were implanted submucosally
      into the pouch in two patients and a reconfigured colon was also used to
      reconstruct a defect of the ureter in one patient. RESULTS: All patients could
      catheterize the pouch easily via the cutaneous stoma without incontinence. No
      complications were noted. CONCLUSIONS: In the event that a urinary diversion is
      necessary for a patient who has previously had radiation therapy, the transverse
      colon pouch can be a useful method to improve the quality of life. In addition,
      versatility of the reconfigured colon segment enables the colon pouch to be
      adapted to adverse clinical situations.

PMID- 12010314
TI  - New simple method of transabdominal ultrasound to assess the degree of benign
      prostatic obstruction: size and horizontal shape of the prostate.
AB  - BACKGROUND: Transabdominal ultrasound has been the standard clinical tool for
      evaluating prostatic size; however, the severity of benign prostatic obstruction
      does not always correspond to the size of the prostate. The purpose of this study
      was to consider the utility of two parameters, (i) the prostatic volume (Pvol)
      and (ii) the ratio of the height : width of the maximum horizontal section of
      prostate (H : W) obtained by transabdominal ultrasound, in screening the degree
      of benign prostatic obstruction. The results were compared with the linear
      passive urethral resistance relation (lin-PURR) obtained by pressure-flow
      studies. METHODS: Fifty-one men with lower urinary tract symptoms were
      prospectively evaluated in regard to urodynamic parameters, transabdominal
      ultrasound volume of the prostate, and calculation of lin-PURR. RESULTS: A
      significant positive correlation was found between Pvol and the degree of benign
      prostatic obstruction. When the ultrasonographic parameters of greater than 30 mL
      Pvol and 0.8 H : W were adopted as provisional cut-off points for detecting
      patients with obstruction, the selected 10 cases had lin-PURR > 3. In addition,
      there were six cases classified with lin-PURR >or= 3 despite the fact that their
      Pvol was less than 30 mL. Their H : W values were > 0.8. CONCLUSIONS:
      Transabdominal ultrasound is useful as a screening test for evaluating the
      prostate. In addition to the size of the prostate, the parameter of the
      horizontal shape (H : W ratio) makes an assessment of the degree of benign
      prostatic obstruction more reliable.

PMID- 12010315
TI  - Efficacy of preoperative donation of autologous blood in patients undergoing
      radical retropubic prostatectomy.
AB  - BACKGROUND: Radical retropubic prostatectomy (RRP) has resulted in substantial
      blood loss and the frequent need for homologous blood transfusion. In this study,
      the efficacy of autologous blood transfusion, from medical and financial
      perspectives, was evaluated in patients undergoing RRP. METHODS: Between 1994 and
      2000, 80 patients with localized prostate cancer underwent RRP in our institute.
      Based on informed consent, preoperative donation of autologous blood (PDA) was
      performed in 65 out of 80 patienets. Four or six units were donated during the
      first 3 years; however, donation units were reduced to a maximum of 4 units since
      1997 onwards. The discard rate of donated blood and frequency of homologous
      transfusion were examined. Changes of hematocrit (Ht) and hemoglobin (Hb) levels
      through donation and surgery and important factors that may affect postoperative
      levels of Ht and Hb were evaluated in 56 patients receiving 4-unit donations.
      RESULTS: Overall, 2 or 4 units of donated blood were discarded in four patients
      and homologous transfusion was required in two patients. In 56 patients receiving
      4-unit donation, the mean Ht level at predonation was 43.3%. Following donation,
      this decreased to 35.7%. The administration of recombinant human erythropoietin
      (rHuEpo) relieved declining Ht levels following donation, but changes in Ht
      levels after surgery were minor. Important factors related to postoperative
      decline of Ht and Hb levels were operative time and blood loss. CONCLUSIONS: The
      program of 4-unit PDA can be performed safely without rHuEpo injection, and it is
      useful to reduce the risk of requiring homologous transfusion. However, more
      efficient programs to relieve patient burden and to reduce medical cost are
      needed.

PMID- 12010316
TI  - Snodgrass procedure for primary hypospadias repair.
AB  - BACKGROUND: In this study, the authors' experience in adaptation of the Snodgrass
      technique for primary hypospadias repair, with an alternative way to create a
      barrier layer of dartos flap for neourethral covering, is presented. METHODS:
      Between March 2000 and January 2001, Snodgrass urethroplasty was consecutively
      done on 24 boys aged between 14 months and 9 years (median: 3 years). The
      position of the meatus was coronal in one boy, at the distal shaft in two, at mid
      shaft in eight, at the proximal shaft in five, penoscrotal in four, scrotal in
      three and perineal in one. Dorsal plication was carried out in nine patients
      (37.5%) to correct residual ventral curvature after penile degloving.
      Postoperatively the neourethra was stented for 10-12 days and suprapubic
      diversion was used for 12-14 days. RESULTS: Postoperative follow up ranged from 4
      to 14 months (median: 8 months). All patients undergoing Snodgrass repair
      obtained a neourethra with a slit-like meatus at the tip of the glans. A small
      urethrocutaneous fistula occurred in one patient with mid-shaft and two with
      proximal-shaft hypospadias (an overall fistula rate of 12.5%). Urethral stricture
      had not been encountered at the time of this report. One patient developed mild
      meatal stenosis and was successfully managed by simple dilatation. CONCLUSIONS:
      The results indicate that Snodgrass urethroplasty provides satisfactory cosmetic
      and functional results and is versatile in repairing almost all types of
      hypospadias.

PMID- 12010317
TI  - Immunological protection induced by bacillus Calmette-Guerin treatment in a
      murine bladder tumor model.
AB  - BACKGROUND: It has been previously reported that MBT-2 tumor growth is completely
      inhibited when mice are inoculated with bacillus Calmette-Guerin (BCG). In this
      study it was examined whether or not vaccination with a mixture of BCG and MBT-2
      cells also induces immunological protection against murine bladder tumors.
      METHODS: Seven hundred thousand MBT-2 cells and 1 mg of BCG (Tokyo 172 strain)
      per mouse were injected subcutaneously into female C3H/HeN mice. Four and eight
      weeks after vaccination with this mixture, animals were reinoculated with MBT-2
      cells alone or MBT-2 cells cocultured with BCG. RESULTS: Animals vaccinated with
      a mixture of BCG and MBT-2 cells showed MBT-2 tumor growth but completely
      rejected the MBT-2 cells cocultured with BCG. MBT-2 cells cocultured with BCG
      developed into tumors when they were inoculated into the control animals.
      Splenocytes prepared from vaccinated animals showed specific cytocidal activity
      against MBT-2 cells precultured with BCG. CONCLUSIONS: The results suggest that a
      mixture of BCG and MBT-2 cells induces antitumor immunological protection against
      BCG- or MBT-2-associated antigens presented on MBT-2 cells precultured with BCG.

PMID- 12010318
TI  - Effects of bladder volume on transabdominal ultrasound measurements of
      intravesical prostatic protrusion and volume.
AB  - BACKGROUND: A filled bladder acts as an acoustic window for transabdominal
      ultrasound measurements of intravesical prostatic protrusion and volume. The aim
      of this study is to evaluate the effects of bladder volume on transabdominal
      ultrasound measurements of these parameters. METHODS: Twenty-two patients
      undergoing transurethral resection of the prostate (TURP) were studied. Under
      general anesthesia just before TURP, a transrectal ultrasound measurement of
      prostate volume was obtained. The bladder was then filled in a stepwise manner
      with 100, 200, 300, 400 and 500 mL. At each volume, the intravesical prostatic
      protrusion and prostatic volume were measured transabdominally using ultrasound.
      RESULTS: There was an obvious trend of decreasing mean transabdominal
      intravesical prostatic protrusions with increasing bladder volume. The mean
      transabdominal intravesical prostatic protrusion at bladder volumes 100, 200,
      300, 400 and 500 mL was 9.1, 8.8, 7.4, 5.8 and 4.6 mm, respectively. The bladder
      volume at which maximum prostatic protrusion occurred was between 100 and 200 mL.
      The mean transabdominal prostate volume at the five increasing bladder volumes
      was 50.6, 48.7, 49.2, 47.9 and 41.4 mL, and these were correlated to transrectal
      prostate volume, particularly when the bladder volume was less than 400 mL.
      CONCLUSIONS: Transabdominal ultrasound measurement of prostatic protrusion is
      dependent on bladder volume. Transabdominal ultrasound measurement of prostatic
      volume correlates well with the transrectal measurement of the same parameter
      when the bladder volume is less than 400 mL.

PMID- 12010319
TI  - Efficacy of 3-D computed tomographic reconstruction in evaluating anatomical
      relationships of colovesical fistula.
AB  - A case of colovesical fistula is reported. The anatomy of the pelvis was
      determined preoperatively with 3-D computed tomography (CT), and the fistula,
      including adjacent structures, could clearly be seen. Compared with conventional
      axial CT imaging, 3-D CT provided better and more complete visualization of the
      anatomical relationships, which facilitated the surgical procedure and provided a
      good outcome.

PMID- 12010320
TI  - Adrenal metastasis from renal cell carcinoma: significance of adrenalectomy.
AB  - BACKGROUND: The present study examined adrenal metastasis resulting from renal
      cell carcinoma (RCC), with the aim of assessing the need for routine ipsilateral
      adrenalectomy during radical nephrectomy. METHODS: Ipsilateral and contralateral
      adrenal metastases were investigated in 256 patients with RCC who had undergone
      radical nephrectomy from 1977 to 1996 at the Tohoku University School of
      Medicine. RESULTS: Twelve of the 256 patients (4.7%) had adrenal metastasis. Ten
      of these 12 patients had progressed to disseminated disease with very poor
      prognosis. Two patients who had solitary adrenal metastases remained disease-free
      for 21 and 7 years. Four patients showed metastases to the contralateral adrenal
      gland. Adrenal metastases in seven of 12 patients were identified by pre- or
      postoperative computed tomography (CT), and in another five macroscopically
      during surgery. CONCLUSIONS: Adrenalectomy was regarded as a possible curative
      treatment for patients with solitary adrenal metastasis. However, the incidence
      of this kind of metastasis was minimal and contralateral adrenal metastases may
      occur in RCC cases. We therefore believe that adrenalectomy should only be
      performed if radiographic evidence reveals metastases in the adrenal gland or if
      gross disease is present at the time of nephrectomy.

PMID- 12010321
TI  - Stage specific follow-up strategy after cystectomy for carcinoma of the bladder.
AB  - BACKGROUND: Follow-up strategies after cystectomy for carcinoma of the bladder
      should be determined according to the risk of recurrence, which is stage
      dependent. We aimed to develop follow-up protocol for monitoring patients with
      carcinoma of the bladder for tumor recurrence and diverted urinary tract
      complications after radical cystectomy. METHODS: The records of 351 patients with
      carcinoma of the bladder who underwent cystectomy between 1979 and 1999 were
      reviewed for dates and presenting symptoms of local and distant recurrences. The
      results of imaging studies and blood tests were also reviewed. Based on the
      division of patients into pathological stages of pT1 and lower, pT2, and pT3 and
      higher groups, we proposed a new follow-up schedule for carcinoma of the bladder.
      RESULTS: The risk of metastasis was related to the pathological stage of the
      primary tumor. Recurrence developed in 10 of 124 patients (8%) with pT1 or lower,
      17 of 101 patients (17%) with pT2, and 55 of 101 patients (54%) with pT3 or
      higher disease at a median of 11 (range 6-186), 10 (1-40) and 7 (1-76) months,
      respectively. Recurrences in patients with pT3 or higher were found earlier and
      more frequently than those with pT2 or lower. Of 82 patients with metastases, 54
      initially were symptomatic, and three of pT1 or lower, six of pT2, and 19 of pT3
      or higher were asymptomatic. Based on these results we proposed a stage specific
      follow-up protocol. CONCLUSIONS: A stage-driven follow-up strategy for monitoring
      patients after radical cystectomy can reduce medical expenses while efficiently
      detecting recurrences and complications.

PMID- 12010322
TI  - Medically and economically appropriate follow-up schedule for prostate cancer
      patients after radical prostatectomy.
AB  - BACKGROUND: Our goal was to determine the optimal frequency and method of follow
      up after radical prostatectomy to minimize medical cost without adversely
      affecting patients. METHODS: Two hundred and twenty-one patients who underwent a
      radical prostatectomy with or without adjuvant androgen deprivation from 1989 to
      1999 were selected for the study. Eighty percent of the patients received
      postoperative androgen deprivation. Tumor recurrence was strictly defined as
      detectable serum prostate specific antigen (PSA) and/or clinical findings such as
      local tumor detection or bone metastasis. Thirty of 221 patients experienced
      tumor recurrence. Risk of tumor recurrence, procedures for detection of
      recurrence, and PSA doubling time after biochemical failure were analyzed.
      RESULTS: None of the 30 patients who were examined showed definitive local
      recurrence or metastatic sites on the imaging study at the time of initial PSA
      detection, and there were no observed recurrences in the absence of detectable
      serum PSA. In patients who showed elevated PSA within 12 months after radical
      prostatectomy, PSA levels rapidly increased with doubling times ranging from 1.2
      to 13.7 months. Excluding those patients, the doubling time of PSA levels ranged
      from 2.8 to 31.5 months. CONCLUSIONS: Prostate specific antigen screening is
      sufficient to detect treatment failure after radical prostatectomy, irrespective
      of adjuvant hormone therapy. Based on the calculated doubling time, the longest
      advisable interval between checks of PSA levels is estimated to be four months
      within the first year after radical prostatectomy, and biannually or annually
      thereafter. Continuously elevated PSA levels or clinical symptoms indicate
      surveys for local recurrences and distant metastases.

PMID- 12010323
TI  - Long-term effects of transurethral microwave thermotherapy.
AB  - BACKGROUND: To identify the clinical valuables predicting a favorable outcome
      after transurethral microwave thermotherapy (TUMT) of the prostate with
      Prostatron. METHODS: One hundred and two patients with lower urinary symptoms
      were treated with TUMT using a Prostatron device with the low-energy protocol
      (Prostasoft version 2.0 J). The pre-operative subjective score and objective
      voiding parameters were collected from the medical record. To test the
      differences in the risk of the necessity for additional treatments for several
      subgroups, Kaplan-Meier survival analyses and log-rank tests were used. RESULTS:
      The Kaplan-Meier analyses showed that 67% of the patients received additional
      treatment within five years. The median period for receiving additional treatment
      was 37 months. The patients with a peak flow rate greater than 6.5 mL per second,
      with a urethral length less than 40 mm, or with an age over 64 years all
      demonstrated a significantly longer period before receiving additional treatment,
      when compared with their counterparts. These three factors were also significant
      in multivariate analysis to predict the long-term outcome. CONCLUSIONS: Overall
      durability of TUMT was limited. Aged patients with a relatively high peak flow
      rate or with a short prostatic urethral length resulted in lower risk of
      receiving additional treatments after TUMT.

PMID- 12010324
TI  - High-dose chemotherapy with peripheral blood stem cell transplantation for
      advanced testicular cancer.
AB  - BACKGROUND: The aim of this study was to investigate the efficacy and safety of
      high-dose chemotherapy (HDCT) for the treatment of patients with advanced
      testicular cancer. METHODS: Fourteen patients were treated with high-dose
      carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin)
      followed by peripheral blood stem cell transplantation. The treatment was used
      for two refractory cases, a second relapse, and for consolidation after the first
      relapse in one case each. It was also used for nine cases as part of the first
      line treatment following primary conventional-dose chemotherapy, and for one case
      as the first salvage for a late recurrent tumor of teratoma with malignant
      transformation. RESULTS: The first two patients who received intensive
      pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two
      patients who were treated with HDCT as the first or second salvage therapy
      achieved successful outcomes. The results for the subsequent nine patients
      (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one
      extragonadal seminoma) were two progressive disease, three no change and four
      partial remission. Only three are alive with NED following salvage surgery.
      Finally, a case of teratoma with malignant transformation did not respond well to
      two cycles of HDCT. There were no marked adverse reactions except one episode of
      severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited
      efficacy of HDCT even in cases with a good to intermediate risk rating according
      to classification by the International Germ Cell Cancer Collaborative Group.
      Because treatment for relapse after HDCT is extremely difficult, new HDCT
      regimens consisting of drugs that are not used in induction chemotherapy need to
      be established.

PMID- 12010325
TI  - Follow-up of clinical stage I testicular cancer patients: cost and risk benefit
      considerations.
AB  - BACKGROUND: Regardless of the way it is managed, a high cure rate has been
      achieved for recurrent low-stage testicular cancer. Achieving a balance between
      survival and the patient's inconvenience and expense during follow-up, has
      therefore become an important issue. METHODS: Prognoses and recurrence patterns
      were investigated in 39 patients with stage I non-seminomatous germ cell tumor of
      the testis (NSGCT), and 82 patients with stage I seminomatous germ cell tumor of
      the testis (SGCT), who underwent high orchiectomy between 1970 and 1997 at our
      institution. We considered the cost benefits and the risks by reviewing our
      results together with other reported results. RESULTS: Patients with clinical
      stage I NSGCT under surveillance showed no progression later than 4 years after
      orchiectomy. The ability to detect progression using chest X-ray alone appeared
      very low. There was no infradiaphragmatic recurrence after adjuvant radiotherapy
      for patients with stage I SGCT. Only two of 204 patients showed progression,
      which included eight of our patients who underwent two cycles of adjuvant
      carboplatin therapy. CONCLUSIONS: Four years of intensive follow-up is probably
      sufficient for patients with stage I NSGCT under surveillance, and routine chest
      X-rays may be required only during the first year of surveillance. The benefit of
      using adjuvant radiotherapy for patients with stage I SGCT is that we could
      remove abdominal and pelvic CT scans from the routine follow-up protocol.
      Randomized trials will clarify whether the adjuvant carboplatin therapy is less
      toxic, provides better prognosis and is more cost-effective than adjuvant
      radiotherapy.

PMID- 12010328
TI  - Neo-adjuvant treatment of infiltrating transitional-cell carcinoma of the bladder
      with paclitaxel and cisplatin: a phase II trial.
AB  - BACKGROUND: A phase II multicentric trial of paclitaxel and cisplatin was
      conducted in previously untreated patients, with locally advanced transitional
      cell carcinoma (TCC) of the bladder, to assess its toxicity and efficiency in
      preserving the bladder. METHODS: Forty-four patients with locally advanced TCC of
      the bladder (seven with T3a, 27 with T3b, and eight with T4a) were treated with
      paclitaxel 175 mg/m(2) over 3 h, and cisplatin 75 mg/m(2) over 30 min, on the
      first day of each 21-day treatment cycle. Therapy was continued for three cycles.
      Patients were re-evaluated and scheduled for radiotheraphy or radical surgery
      depending on tumoral response. Tumoral response was measured by citology,
      computed tomographical scans, and deep randomized biopsies of the bladder.
      RESULTS: Thirty-two out of 42 patients (76%; 95% confidence interval 45-93%)
      showed a major response (22 complete, and 10 partial). Response times ranged from
      18 to 54 months. Three patients with T4 bladder primary tumors experienced a
      pathological CR. At a median follow-up of three years, 20 patients remain free of
      disease (47.6%), six patients are alive with disease (14.3%), 12 patients died of
      disease (28.5%), and four others died of unrelated causes (9.5%). Hematological
      toxicity included anemia, thrombocytopenia, and neutropenia. No grade four
      febrile neutropenia was observed. Non-hematological toxicity included alopecia
      (93.2%), diarrhea (11.4%), vomiting (18.5%) mucosytis (4.6%), and neuropathy
      (4.6%). Drug omissions or dose delay for adverse events were only necessary in
      one patient (2.2%), and three patients (6.8%), respectively. CONCLUSIONS:
      Paclitaxel and cisplatin is an active and well-tolerated neo-adjuvant regimen for
      previously untreated patients with pure TCC of the bladder, achieving a vesical
      preservation rate of 52%.

PMID- 12010329
TI  - Utility of immunohistochemical detection of prostate-specific Ets for the
      diagnosis of benign and malignant prostatic epithelial lesions.
AB  - BACKGROUND: Human prostate-specific Ets (hPSE) belongs to the Ets family. It
      regulates the proliferation, differentiation, and development of prostate
      epithelial cells. A recent study showed that hPSE can be detected in normal
      glands but not in cell lines established from prostate cancer (PCA), suggesting a
      translational disorder of hPSE from mRNA to protein in PCA. Immunohistochemical
      detection of hPSE could therefore be another method of differential diagnosis of
      PCA from other proliferative conditions in the prostate. METHODS: An
      immunohistochemical detection of hPSE was carried out on the whole mounted
      prostatectomy specimen obtained from 19 cases with PCA. RESULTS: Basal and
      secretory luminar cells showed a diffuse cytoplasmic staining for hPSE in normal
      glands, hyperplastic glands, and prostate intraepithelial neoplasia lesions.
      Whereas approximately 30% of PCA lesions showed a negative staining for hPSE, the
      positive rate for hPSE between PCA and benign glands or prostate intraepithelial
      neoplasia (PIN), was statistically significant (P < 0.05). Staining intensities
      in normal glands, hyperplastic glands, and PIN lesions were similar, but
      generally stronger than those in PCA lesions. CONCLUSIONS: Negative
      immunoreactivity for hPSE strongly suggests malignancy in the prostate glands.
      Decreased immunoreactivities of glands for hPSE could suggest PCA.

PMID- 12010330
TI  - Bilateral testicular tumors: a report of nine cases with long-term follow-up.
AB  - BACKGROUND: The incidence and clinical features of bilateral germ cell testicular
      tumor (GCTT) in the Japanese population are not fully characterized. We examined
      the incidence, clinical features, management and outcome, sexual status, hormonal
      environment, implication of androgen replacement, and human leukocyte antigen
      (HLA) typing of bilateral GCTT. METHODS: We treated nine consecutive patients
      with bilateral GCTT from 1980 through to 1999, and reviewed their hospital and
      clinic charts. Testosterone, luteinizing hormone, follicle stimulating hormone,
      dehydroepiandrosterone, and dehydroepiandrosterone-sulfate were measured in
      bilateral orchiectomized patients. Human leukocyte antigen typing was assessed
      with peripheral lymphocyte. RESULTS: The incidence of bilateral GCTT against the
      total number of patients with GCTT was 9/274 (3.3%). The median age of the first
      tumor was 29 (range 21-75) years. Three cases were synchronous and the remaining
      six cases were metachronous. In the case of metachronous tumor, the median
      interval between first and contralateral tumor was 8 (range 2-25) years. Standard
      treatment was defined as surveillance policy in stage I, chemotherapy for higher
      stages of non-seminoma, and radiotherapy for stage II seminoma. Human leukocyte
      antigen typing was examined for seven cases. Five cases were positive for HLA
      A24. The incidence of HLA-A24 in bilateral GCTT was identical to that of the
      Japanese population. The relapsing incidence of stage I disease with surveillance
      policy was almost identical to unilateral GCTT. A 74-year-old patient with stage
      II seminoma died of the disease at 1.3 years. The other eight patients remained
      well without any evidence of recurrence at a median follow-up period of 78 (range
      12-204) months. Four patients with bilateral orchiectomy did not require androgen
      replacement without easy fatigability. Sexual status was conserved using androgen
      replacement. CONCLUSIONS: Long-term follow-up, as long as 25 years, is
      recommended for contralateral relapse. Some patients with bilateral orchiectomy
      do not require androgen replacement. The significance of HLA-A24 for bilateral
      testicular tumor is equivocal in the Japanese population.

PMID- 12010331
TI  - Lymphangioma of the kidney.
AB  - Lymphangiomas are rare benign tumors that are congenital malformations of the
      lymphatic system. Most cases present in children as a soft, cystic mass in the
      neck and the axilla. Primary renal lymphangioma is exceedingly rare, with only 35
      cases reported so far. We report a case of primary lymphangioma arising from the
      kidney. A 59-year-old man was referred for evaluation of a right renal mass found
      in an abdominal ultrasonography during a health checkup. Abdominal
      ultrasonography and computed tomography (CT) revealed a 3.2 x 2.9 cm
      multiloculated cystic mass in the upper pole of the right kidney. We could not
      deny malignant disease such as cystic renal cell carcinoma with any diagnostic
      modalities. The patient was brought to surgery. During the surgical procedure,
      the tumor was suspected to be lymphangioma of the kidney as a result of a frozen-
      section histopathological evaluation. Therefore enucleation of the tumor was
      performed. Pathological evaluation of the specimen revealed lymphangioma arising
      from the kidney. The patient is free of disease after a 3-month follow-up period.

PMID- 12010332
TI  - Spontaneously ruptured multilocular cystic nephroma.
AB  - Multilocular cystic nephroma is a relatively rare benign tumor of the kidney. An
      adult case of spontaneously ruptured multilocular cystic nephroma was reported. A
      33-year-old woman who presented with a right flank colic attack. The preoperative
      diagnosis was spontaneously ruptured renal tumor. A right nephrectomy was
      performed. A multilocular cystic lesion, 10 cm in diameter, was found in the
      removed specimen, which had a hematoma inside and direct tumor extension into the
      renal pelvis. On microscopic examination, the surface of loculi was covered by a
      layer of hobnail epithelium, and septa were composed of fibrous tissue with
      dilated vessels, lacking in normal renal components. There were no signs of
      malignancy. The lesion extending into the renal pelvis showed the same
      microscopic findings. The final diagnosis was multilocular cystic nephroma. Two
      respects, spontaneous rupture and tumor extension into the renal pelvis, were
      unique to the present case. There has been no report of spontaneously ruptured
      mutilocular cystic nephroma. The tumor extension into the renal pelvis, however,
      has been found in several reports. This growth pattern might be one of the
      characteristics of this benign renal tumor.

PMID- 12010333
TI  - Prolonged liver dysfunction caused by hemosiderosis in a renal transplant
      recipient.
AB  - BACKGROUND: Liver dysfunction is a frequent complication that arises in the
      period following kidney transplantations, often resulting in death. We reported a
      case proving hemosiderosis as a cause of prolonged liver dysfunction after
      cadaveric kidney transplantation. METHODS: A 47-year-old man, who had been
      undergoing hemodialysis, was referred to our hospital on 2 November 1999. On the
      same day, cadaveric kidney transplantation was performed, and serum creatinine
      level reached a normal level within 2 weeks after surgery. However, serum
      transaminase gradually increased in the postoperative period. Serum ALT rose up
      to 116 IU/L on day 20 after the operation and 215 IU/L on day 30. Microscopic
      examination by needle biopsy revealed hemosiderosis of the liver. Recombinant
      human erythropoietin was administered and phlebotomy was performed. Liver
      function improved as a result. CONCLUSION: Early histological diagnosis can be a
      useful marker in predicting the course of chronic liver disease.

PMID- 12010334
TI  - Endoscopic partial cystectomy for bladder leiomyoma using retroperitoneoscopic
      and transurethral procedures.
AB  - Retroperitoneoscopic partial cystectomy was performed to remove a leiomyoma in
      the right wall of the bladder in a 58-year-old man. The tumor was initially
      circumscribed with a mucosal incision using a transurethral resectoscope, and
      once the bladder wall had been penetrated with the resectoscope, the remaining
      procedures were performed retroperitoneoscopically. The bladder wall was closed
      using a retroperitoneoscopic suturing technique. Endoscopic partial cystectomy
      using both a transurethral incision and a retroperitoneoscopic resection is
      technically feasible in the treatment of small bladder tumors.

PMID- 12010335
TI  - Cutaneous amyloidosis and possible association with systemic amyloidosis.

PMID- 12010337
TI  - Comparison of two surgical approaches for treating vitiligo: a preliminary study.
AB  - BACKGROUND: Surgical techniques have recently been introduced for patients with
      vitiligo. Randomized controlled trials have not been performed. AIM: To compare
      the efficacy and side-effects of two surgical methods (suction blister vs. thin
      split-thickness graft technique) for the treatment of vitiligo. METHODS: Three
      suction blisters, approximately 0.8 cm in diameter, made with a special tool
      attached to a vacuum extractor, which were converted to erosions by removal of
      the roofs of the bullae, and one round erosion of approximately the same
      diameter, made using a silver knife, were created. One roof of a blister and two
      cutaneous thin split-thickness grafts taken from the gluteal region were
      transferred onto recipient vitiliginous areas; one was left alone. The results
      were evaluated by one non-blind and two blind observers bimonthly during the 3
      month follow-up period. RESULTS: Repigmentation rates were 25-65% in the suction
      blister technique and 90% in the thin split-thickness graft technique (P <
      0.001). CONCLUSIONS: The thin split-thickness graft technique is superior to the
      suction blister technique in treating vitiligo.

PMID- 12010338
TI  - Lymphocyte subtypes and adhesion molecules in actinic prurigo: observations with
      cyclosporin A.
AB  - BACKGROUND: Actinic prurigo is a photodermatitis in which UV light is implicated
      by an unknown mechanism. METHODS: Skin biopsies of 19 patients with actinic
      prurigo and 11 controls were analyzed by immunohistochemistry. RESULTS: In
      actinic prurigo patients, there was a significant increase in the number of CD3,
      CD4, CD8, CD45RA, CD45RO, and CD45RB lymphocytes and Langerhans cells, as well as
      in the level of human leukocyte antigen-DR (HLA-DR) expression and cell adhesion
      molecules lymphocyte functional antigen-1 (LFA-1), intercellular adhesion
      molecule-1 (ICAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1).
      Actinic prurigo patients were treated with cyclosporin A (CsA), and a final skin
      biopsy was taken after 6 months of treatment. All the cell populations and
      markers studied, except for the CD4 lymphocytes, Langerhans cells, and HLA-DR
      expression, returned to normal levels. CONCLUSIONS: CsA was found to be effective
      in relieving the clinical symptoms of actinic prurigo.

PMID- 12010339
TI  - Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis:
      a study of the clinical course and evaluation of the immunoglobulin E serum
      levels.
AB  - BACKGROUND: Vitamin E (VE) is a potent antioxidant that can improve the immune
      macrophage-mediated response, decrease the production and/or release of
      prostaglandins in humans, and decrease the serum levels of immunoglobulin E (IgE)
      in atopic subjects. AIM: To compare the effects of placebo (PL) and VE intake
      (400 IU/day) on subjective symptoms and serum IgE levels in 96 subjects with
      atopic dermatitis. MATERIALS AND METHODS: A single-blind clinical analysis was
      performed on 96 subjects randomly divided into two groups. Fifty subjects were
      given orally 400 IU (268 mg) of VE of natural origin, once a day for 8 months,
      and 46 took PL for the same period. Complete blood count, serum IgE levels,
      radioallergosorbent test (RAST) score, antinuclear antibodies (ANA), and
      biochemical analysis were obtained at the time of enrollment and every 15 days
      during the 8 months of the study. To evaluate VE therapy, a questionnaire was
      sent to each subject for completion at the end of the study. RESULTS: The results
      were as follows: (A) four subjects treated with VE worsened, compared to 36 in
      the PL group; (B) six subjects in the VE group and five in the PL group showed no
      change; (C) slight improvement was observed in 10 subjects in the VE group and
      four in the PL group; (D) 23 of the 50 subjects treated with VE showed great
      improvement, compared to only one in the PL group; and (E) there was almost
      complete remission of atopic dermatitis in seven of the 50 subjects in the VE
      group, but none in the PL group. Females showed less progression of atopic
      dermatitis than males in both groups and a higher percentage of almost complete
      remission (five females and two males). The range of serum IgE levels varied
      markedly from 1005 to 490 IU/mL in the VE group and from 1239 to 812 IU/mL in the
      PL group over 8 months. Subjects with great improvement and near remission of
      atopic dermatitis in the VE group demonstrated a decrease of 62% in serum IgE
      levels based on initial conditions, while, in subjects taking PL, the difference
      was approximately 34.4%. No complications were observed in either group. A
      remarkable improvement in facial erythema, lichenification, and the presence of
      apparently normal skin was reported. Eczematous lesions healed mostly as a result
      of decreased pruritus. CONCLUSIONS: The correlation between VE intake, IgE
      levels, and the clinical manifestations of atopy indicates that VE could be an
      excellent therapeutic tool for atopic dermatitis.

PMID- 12010340
TI  - Atopic dermatitis is associated with a decrement in health-related quality of
      life.
AB  - BACKGROUND: Although atopic dermatitis is a chronic skin disease that can have a
      major impact on a patient's life, the burden of illness associated with this
      condition has not been well characterized. OBJECTIVE: To determine the health
      related quality of life (HRQL) of patients with atopic dermatitis by disease
      severity and to compare it with that of the general public and of patients
      suffering from other chronic illnesses or skin disorders. METHODS: Two hundred
      and thirty-nine atopic dermatitis patients aged 4-70 years completed the Medical
      Outcomes Study Short Form-36 Health Survey (SF-36) and the Dermatology Life
      Quality Index (DLQI) or the Children's Dermatology Life Quality Index. These HRQL
      scores were compared by self-reported patient disease severity ratings. Health
      related quality of life scores were compared with those of the general population
      and those of patients with other chronic conditions (clinical depression,
      hypertension, type 2 diabetes) or skin disease (psoriasis). Dermatology Life
      Quality Index scores were also compared with those of other skin diseases (such
      as psoriasis, Darier's disease, and Hailey-Hailey disease). RESULTS: Patients
      with atopic dermatitis had inferior scores on the SF-36 vitality, social
      functioning, and mental health subscales compared with individuals in the general
      population. In seven of eight subscales, individuals reporting more severe
      disease had inferior DLQI and SF-36 scores. Patients with atopic dermatitis had
      inferior mental health scores compared with those with diabetes or hypertension,
      and inferior social functioning scores compared with patients with hypertension.
      When compared with a psoriasis cohort, patients with atopic dermatitis had
      inferior scores in the role-physical, vitality, social functioning, role
      emotional, and mental health SF-36 domains. Patients with atopic dermatitis had
      similar DLQI scores to patients with other chronic dermatologic diseases.
      CONCLUSIONS: These results demonstrate that atopic dermatitis has an impact on
      HRQL, particularly in social functioning and psychological wellbeing. Patient
      assessed severity of atopic dermatitis correlates with HRQL decrements,
      indicating greater HRQL impact with greater disease severity. Atopic dermatitis
      has as large an impact on HRQL as several chronic conditions and other
      dermatologic conditions.

PMID- 12010341
TI  - Clinical and epidemiological observations of cutaneous tuberculosis in Larkana,
      Pakistan.
AB  - BACKGROUND: Cutaneous tuberculosis is widespread in Pakistan but has not been
      fully documented. This study was conducted to determine the clinical pattern,
      nature and existence of the disease in Larkana, Sindh province, Pakistan.
      METHODS: We are reporting 153 cases of patients with cutaneous tuberculosis who
      visited our department from 1996 to 1999. All cases were diagnosed at the clinic,
      and the biopsies were examined for histopathological evidence. The patients
      received three antituberculous treatments during a 9 month course. RESULTS:
      Clinically, 63 (41.2%) cases of lupus vulgaris, 54 (35.3%) of scrofuloderma, 29
      (19.59%) of lupus verrucosa cutis, six (3.92%) of tuberculosis cutis orificialis
      and one (0.64%) case of disseminated cutaneous tuberculosis were observed in our
      department from 1996 to 1999. All patients were aged between 3 and 50 years and
      had experienced the present complaints for 1 to 12 years. Sixty-nine (45.1%)
      cases were children aged under 10 years, 50 cases (37.25%) were aged between 10
      and 20 years, and 27 cases (17.65%) were aged over 20 years. There was no
      considerable ratio difference of the disease between male and female patients.
      Histopathologically, all the specimens showed chronic granulomatous changes; the
      majority was infiltrated with epitheloid cells, langhans giant cells, plasma
      cells and other inflammatory cells, such as lymphocytes, eosinophils and
      neutrophils in ulcerated lesions. Increased numbers of mast cells were seen in
      upper and lower dermis in two-thirds of the specimens. Caseating necrosis was
      visible in half of the specimens while Ziehl-Neelsen stain was negative in all
      the sections. CONCLUSIONS: The observed number of patients was moderately large,
      thus indicating a high incidence of cutaneous tuberculosis in Larkana. Lupus
      vulgaris, a form of cutaneous tuberculosis, was widespread in this area and
      prevalent in adults, while scrofuloderma was prevalent in children. Moreover, the
      existing rate of the disease was higher in children aged under 10 years and lower
      in adults. This indicates that children are more prone to this disease than
      adults.

PMID- 12010342
TI  - Pathergic pyoderma gangrenosum in a venous ulcer.
AB  - A 74-year-old woman was referred to our department in December 1999 for a
      pyoderma gangrenosum (PG) arising at the edges of chronic leg ulcer. The history
      was positive for benign monoclonal gammopathy, ischemic hypertensive cardiopathy,
      polyarthrosis and venous lower leg deficiency. Monoclonal gammopathy of IgA Kappa
      type was diagnosed 10 years before with a continued benign nature. In 1990 a post
      traumatic PG of the left leg was diagnosed and a therapy with Cyclosporine A was
      started with healing of the lesion. In June 1999, 6 months before the
      hospitalization, a typical venous ulcer of the right leg appeared and was treated
      with bed-rest, compression bandaging and topical desloughing therapy. In the last
      month, after a minor surgical debridement of the wound, the lesion developed
      pustules evolving into a painful, necrotic ulcer with ragged, purple-red,
      undetermined borders (Fig. 1). A relapse of PG was suspected. Histological
      examination was consistent with pyoderma gangrenosum and showed massive
      neutrophilic infiltration, hemorrhage and necrosis of the overlying epidermis.
      Wound culture was negative. Other laboratory examinations only showed IgA = 8.15
      g/L. Investigation of other underlying medical conditions were normal or
      negative. The venous leg ulcer gradually healed with antiseptic and compression
      bandage therapy. After a 4-month course of topical steroid therapy with good
      results, the PG recurred also involving the proximal area of the leg.
      Methylprednisolone 50 mg/day was started. Healing began 10 days later and 2
      months later the wound healed and epithelialized. Steroid was reduce to 5 mg
      daily for 4 months. No recurrence was seen when the drug was stopped.

PMID- 12010343
TI  - S-100-negative atypical granular cell tumor: report of a case.
AB  - A 38-year-old man presented with a solitary, round, 1.2 x 1.2 cm, bluish-colored,
      dome-shaped, hard nodule on the left side of the neck, which had grown over 2
      months (Fig. 1). The nodule was nontender and nonmovable. Light microscopy
      revealed that the neoplasm was situated in the reticular dermis with extension
      into the papillary dermis. The tumor showed expansile growth with smooth and
      round borders, and was made up of sheets of cells arranged in nests or lobules
      separated by thin delicate connective tissue septa. The tumor cells were round,
      oval, or polygonal in shape with distinct cellular borders. The cells had
      abundant eosinophilic granular cytoplasm, and considerable variation of cellular
      and nuclear size was noted (Fig. 2a). The tumor cell nuclei were vesicular and
      some had pleomorphism (Fig. 2b). Sometimes multiple nucleoli were seen. Mitoses
      and necrosis were virtually absent. Immunohistochemical staining revealed that
      some of the cytoplasmic granules stained positively with periodic acid-Schiff
      (PAS) after diastase treatment. Tumor cells showed strong reactivity for CD68 and
      neuron-specific enolase, and negative results for S-100, factor XIIIa,
      cytokeratin, desmin, CD34, and smooth muscle actin. Electron microscopy revealed
      that the tumor was composed of polygonal cells with round to irregular nuclei,
      and the cytoplasm contained numerous secondary lysosomes. The tumor was
      completely excised.

PMID- 12010344
TI  - Dyskeratosis congenita with isolated neutropenia and granulocyte colony
      stimulating factor treatment.
AB  - A 3-year-old Turkish boy with a history of chronic cough, recurrent
      bronchopneumonia, and a borderline sweat chloride test (40 mEq/L) was referred
      for further evaluation to our department. He was born at term (2100 g) to a
      marriage with no consanguinity. His mother and father were 40 and 46 years old,
      respectively. Physical examination (Fig. 1) revealed hypopigmented, atrophic, and
      hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation on the
      entire body, predominantly on the face, neck, arms, shoulders, and legs, which
      had been noticed initially at the age of 18 months. Dystrophic toenails, sparse
      and thin hair, and phimosis were also observed. Laboratory tests disclosed an
      isolated neutropenia (white blood cell count, 1800/mm3). Bone marrow (BM)
      aspiration showed a decreased myelopoiesis without myelodysplastic changes, but
      normal erythropoiesis, megakaryopoiesis, and normal stroma. Lymphocyte subgroups
      containing CD4, CD5, CD6, CD8, CD19, CD23, and CD25, and immunoglobulin G (IgG),
      IgM, IgA, and IgE, were in the normal range; hemoglobin F (HbF), 2.8%.
      Spontaneous and clastogen-induced chromosome breaks were not increased. A skin
      biopsy showed increased pigmentation at the basal layer, dyskeratotic epidermal
      cells, and marked IgM deposition and cytoid bodies and mild IgA and IgG deposits
      at the dermo-epidermal junction. Lactate response to glucose challenge, amino
      acid chromatography, and urine organic acid analysis were normal. A diagnosis of
      dyskeratosis congenita (DC) was made with typical skin lesions, dystrophic
      toenails, thin and sparse hair, and neutropenia with decreased myelopoiesis in
      BM. Treatment with granulocyte colony-stimulating factor (G-CSF) was considered
      for the neutropenia. As the increase in neutrophil count at a dose of 5 microg/kg
      was not adequate, 10 microg/kg G-CSF was tried (Fig. 2). With 10 microg/kg once
      to three times a week, a 1.8-4.8-fold increase in the absolute neutrophil count
      (ANC) was achieved with no side-effects. Treatment was more frequent during
      infection (days 22-28).

PMID- 12010345
TI  - Erythema nodosum associated with reactivation tuberculous lymphadenitis
      (scrofula).
AB  - A 73-year-old African American female presented to our clinic with painful lower
      extremity lesions of 2 weeks duration. She was in her usual state of health until
      3 months prior to presentation when she reported symptoms of fatigue and
      weakness. She also noticed an enlarging mass on the left side of her neck. She
      denied fevers, chills, night sweats or cough. Her symptoms were unresponsive to a
      course of oral dicloxacillin. The neck mass enlarged over 8 weeks and she was
      referred to our institution for evaluation. CT scan of the neck showed an
      enlarged lymph node. Ten days prior to her presentation in dermatology, a fine
      needle aspirate of the enlarging lymph node revealed necrotizing granulomas.
      Tissue was sent for routine mycobacterial and fungal cultures. Routine blood
      work, chest radiograph, and a tuberculin skin test were also performed. At the
      time of her dermatology visit she described the development of multiple new
      painful, non-pruritic lesions, bilaterally on the lower extremities. She also
      reported a red crusted area that appeared at the site of her tuberculin test that
      was placed subsequent to the development of her lower extremity lesions. Her past
      medical history was significant for Parkinson's disease, hypothyroidism and
      hypertension. Her current medications included l-thyroxine, estrogen and
      diltiazem. Her travel history was only remarkable for a trip to Jamaica the
      previous spring. She was born and raised in Haiti. She reported a history of a
      positive tuberculin skin test 20 years ago, but received no therapy. Physical
      examination revealed a 2 x 3 centimeter firm, nontender left lateral neck mass
      (Fig. 1). Her right forearm revealed an erythematous, ulcerated, indurated plaque
      1.5 cm in diameter (Fig. 2.). Her lower extremities revealed tender 0.5 to 1 cm
      erythematous nodules below the knees bilaterally (Fig. 3). A punch biopsy of a
      lower extremity nodule revealed a mild pervisacular dermal infiltrate. Within the
      subcutaneous tissue there was septal widening. There was also a lymphohistiocytic
      infiltrate with a slight admixture of neutrophils within the septa of the fat
      lobules. There was no evidence of necrotizing vasculitis or collagen necrosis. An
      acid-fast stain was not performed. The histologic findings were consistent with a
      diagnosis of erythema nodosum. Her laboratory evaluation including CBC,
      electrolytes, thyroid studies, angiotensin converting enzyme level and chest
      radiograph were normal. Approximately 1 week after her dermatological evaluation,
      the fine-needle aspirate culture grew Mycobacterium tuberculosis. A diagnosis of
      tuberculous lymphadenitis associated with erythema nodosum was confirmed. The
      patient was started on quadruple therapy of isoniazid, rifampin, ethambutol and
      pyrazinamide. Her lower limb skins lesions rapidly resolved over the subsequent
      month and her neck mass also diminished in size. She completed 6 months of
      antituberculous therapy with complete resolution of her lymphadenopathy.

PMID- 12010346
TI  - Two Japanese cases of localized involutional lipoatrophy.
AB  - We present two Japanese cases of involutional lipoatrophy. The first case is that
      of a 30-year-old woman, who first appeared at our hospital complaining of a
      localized, well-demarcated depression, approximately 3 x 4 cm in size, normal to
      slightly erythematous in coloration, on the lateral side of the left upper arm
      (Fig. 1a). The condition was asymptomatic, and she had noticed this anomaly a
      month prior to consultation. She received intramuscular injections of
      corticosteroids of unknown dosage at the affected site for the treatment of
      allergic rhinitis 4 months prior to her present consultation. The second patient,
      a 23-year-old woman, appeared at our hospital complaining of a similar macule 4 x
      4 cm in size, which she noticed several weeks prior to her most recent
      consultation. She had no history of injury or injection at the site before the
      development of the condition (Fig. 1b). She had been under treatment for atopic
      dermatitis since early childhood and was treated only with topical applications
      of white petrolatum containing 2% salicylic acid for the past several years. In
      order to rule out the possibility of acquired partial lipodystrophy associated
      with localized scleroderma, lupus profundus and the other connective tissue
      diseases, a histological examination was performed for both patients.
      Histopathological analysis of the region exhibited a well-defined fat lobule
      composed of numerous small adipocytes (Fig. 1c) embedded in hyaline connective
      tissue. Edema and dilated capillaries were noticeable in the subcutaneous tissue
      surrounding the area. Inflammatory cells were not prominent, although mononuclear
      cells were observed in both patients. No epidermal change was seen in either
      patient. Direct and indirect immunofluorescence studies revealed no deposits of
      immunoreactants in the skin of either patient. Immunohistochemical studies with
      the antibody against macrophage (anti-CD68 antigen; DAKO.) showed that positive
      cells were scattered around blood vessels and shrunken lipocytes in the
      subcutaneous tissues (Fig. 1d). Most of these cells in the fat lobules were also
      positive for mucin stains such as Alcian blue. No abnormal findings came to light
      in the ordinary hematological and blood chemistry examinations of both patients.
      The autoantibody screening tests using antinuclear, anti-DNA, anticentromere, and
      anti-Scl-70 antibodies were negative in both patients.

PMID- 12010347
TI  - Primary malignant melanoma of the oral cavity: case report.
AB  - An 80-year-old-female patient had a pigmented lesion on: the hard palate, the
      soft palate, the alveolar mucosa and the vestibular mucosa of the maxillary
      gingiva. Pigmented macules and patches had been persistent and asymptomatic for
      many years (Fig. 1). The lesion exhibited irregularities of pigmentation, border
      and surface contour. About 1 year later the patient had noticed an extension of
      the pigmented macules and plaques; there was also the appearance of nodules of
      the maxillary gingiva accompanied by swelling. Loosening of teeth as a result of
      extensive destruction of bone was further noted (Fig. 2). The histological
      examination showed a downward streaming in the dermis of the tumor cells and a
      disintegration and ulceration of the epidermis (Fig. 3). An increased number of
      large round or polygonal cells resembling atypical epithelioid cells were found
      on the submucosa. The atypical cells had enlarged, pleomorphic nuclei with
      prominent and sometimes multiple nucleoli. Mitoses were observed at various
      tissue levels (Fig. 4). Abundant pigmented melanin was present in the tumor cells
      (Fig. 5). Many cells had fine, dusty melanin particles. The tumor cells showed
      great variations in size. Immunohistochemical staining, with S100 protein and
      HMB45 antibodies, stained many of the spindleshaped cells, indicating that they
      were melanocytic cells. An inflammatory infiltrate of lymphocytes was seen in a
      band beneath the invading tumor cells.

PMID- 12010348
TI  - Cutaneous involvement of dermatomyositis can respond to Dapsone therapy.
AB  - BACKGROUND: Dapsone (4,4-diaminodiphenylsulfone) is a sulfone antibiotic used in
      the treatment of leprosy, but dermatologists more commonly utilize its anti
      inflammatory properties particularly directed against leukocytes to treat various
      bullous disorders, erythema nodosum, pyoderma gangrenosum, Sweet's syndrome,
      cutaneous vasculitis, and cutaneous forms of lupus erythematosus. The cutaneous
      manifestations of dermatomyositis are often resistant to antimalarial and
      immunosuppressive therapies. METHODS: Two patients with cutaneous dermatomyositis
      unresponsive to combination therapy with prednisone, hydroxychloroquine,
      quinacrine, and immunosuppressive medications had Dapsone added to their therapy.
      RESULTS: Both patients showed rapid improvement with the addition of Dapsone.
      Each had an exacerbation of their cutaneous dermatomyositis on Dapsone with
      withdrawal and subsequent improvement when the Dapsone was reinstituted.
      CONCLUSIONS: Dapsone therapy for cutaneous dermatomyositis may have a wider role
      in treatment for these patients refractory to prednisone and antimalarial
      therapy.

PMID- 12010349
TI  - Benzoyl peroxide: a history of early research and researchers.

PMID- 12010350
TI  - Alopecia areata: past perceptions.

PMID- 12010351
TI  - Wearing sunglasses--a risk factor for the development of cutaneous malignant
      melanoma?

PMID- 12010353
TI  - HIV-related morbidity and mortality in patients starting protease inhibitors in
      very advanced HIV disease (CD4 count of < 50 cells/microL): an analysis of 338
      clinical events from a randomized clinical trial.
AB  - BACKGROUND: AIDS defining events occur infrequently in the presence of CD4 counts
      above 200 cells/microL. It is, however, uncertain for most of the AIDS defining
      conditions whether this threshold can be considered equally safe in patients with
      a previously very low CD4 nadir. METHODS: We evaluated in detail all the AIDS
      defining events observed during a 48-week clinical trial in 1251 nucleoside
      reverse transcriptase inhibitor-experienced patients who started protease
      inhibitors (PIs) at CD4 counts below 50 cells/microL. The type of event,
      immunological status at the moment of event and time between start of PI
      treatment and event occurrence were analysed cumulatively and by event type;
      event rates were calculated. RESULTS: Concomitant data on CD4 counts were
      available for 338 AIDS defining events (81% of total events). Median time between
      start of treatment with PI and event was 94.5 days and median absolute CD4 value
      at the occurrence of event was 20 per microL. Only 14 events (in 12 patients)
      were observed above the threshold of 200 CD4 cells/microL. An analysis of the 67
      deaths with concomitantly available CD4 counts (57%) showed a median CD4 count of
      10 cells/microL, with only four deaths occurring in the presence of a CD4 count
      above 100 cells/microL. CONCLUSIONS: Very few clinical AIDS defining conditions
      were observed in patients who start PIs at very low CD4 counts and with treatment
      restore absolute values in CD4 counts above 200 cells/microL. This threshold can
      therefore be considered a clinically effective goal of treatment with respect to
      occurrence of all AIDS defining conditions in patients starting PIs in very
      advanced HIV disease.

PMID- 12010354
TI  - Body composition changes in protease inhibitor-naive HIV-infected patients
      treated with two nucleoside reverse transcriptase inhibitors.
AB  - OBJECTIVES: In the era of highly active antiretroviral treatment (HAART), there
      are insufficient data regarding lipodystrophy syndromes in HIV-1-infected
      patients treated with regimens that do not include protease inhibitors (PIs). We
      studied changes in body composition in HIV-1-infected patients before and 2 years
      after starting a non-PI-containing antiretroviral treatment regimen. METHODS: We
      studied retrospectively the whole body dual energy X-ray absorptiometry (DEXA)
      scans of 23 PI-naive HIV-1-infected patients (17 males, six females), aged 37.4
      +/- 9.3 years with mean CD4 count 401 +/- 130 cells/microL. Thirteen patients
      were on zidovudine (ZDV) + lamivudine (3TC) and 10 on ZDV + didanosine (ddI).
      Subjects were evaluated before the beginning of antiretroviral treatment and
      approximately 24 months later. For each patient body weight, CD4 T-cell counts,
      bone mineral content (BMC), bone mineral density (BMD) and whole body as well as
      regional fat and lean body mass were evaluated. RESULTS: A significant decrease
      in BMC was observed, although the T scores remained within the normal limits. Our
      patients also exhibited a significant decrease in body weight due almost
      exclusively to fat loss, while lean mass was minimally affected. Fat loss was
      statistically significant in the arms and legs, but not in the trunk. The above
      changes were most prominent in the ZDV + 3TC treatment group; in this group of
      patients, fat loss was also evident in the trunk. Patients on ZDV + ddI, on the
      other hand, only showed a significant increase in their legs' lean mass; they
      preserved their total fat mass and exhibited no other significant changes between
      the two assessments. CONCLUSIONS: Dual NRTI therapy contributes to fat loss and
      reduction of bone mineral content in otherwise healthy, clinically stable, PI
      naive HIV-infected adults. Compared with patients on ZDV + ddI, patients on ZDV +
      3TC had a more prominent fat loss in all body regions.

PMID- 12010355
TI  - Heterozygosity for CCR5-Delta32 but not CCR2b-64I protects against certain
      intracellular pathogens.
AB  - OBJECTIVE: To determine the association between CCR5 and CCR2b genotype and the
      clinical manifestation of first and subsequent AIDS-defining illnesses (ADIs).
      METHODS: The distribution of ADIs was examined by CCR5 and CCR2b genotype in a
      subset of homosexual men enrolled in the Sydney AIDS Prospective Study. The
      expected number of ADIs was calculated from rates observed in the same tertiary
      hospital over the same period. RESULTS: Information on initial ADI was collected
      for 117 homosexual men diagnosed with AIDS before January 1998. Of these
      individuals, 17 were heterozygous for the CCR5-Delta32 mutation and 11 were
      heterozygous for CCR2b-64I. The number of observed cases of Pneumocystis carinii
      pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) and
      cryptosporidiosis reported as a first ADI was substantially fewer in people
      heterozygous for the CCR5-Delta32 mutation than for those without the mutation,
      despite similar age, CD4 T-cell count at AIDS diagnosis, year of AIDS diagnosis
      and receipt of antiretroviral treatment. In addition, among individuals
      heterozygous for CCR5-Delta32 there were fewer cases of PCP, toxoplasmosis, MAC,
      and cryptosporidiosis observed as subsequent ADIs compared to the number
      expected, based on rates measured in the same hospital during the same period
      (seven observed vs. 24 expected, RR = 0.3, 95% CI = 0.01-0.6). The distribution
      of first and subsequent ADIs did not differ from the number expected in
      individuals heterozygous for the CCR2b-64I mutation. CONCLUSION: Results from
      this study show that heterozygosity for CCR5-Delta32 but not CCR2b-64I appears to
      protect against opportunistic infections.

PMID- 12010356
TI  - The effect of ritonavir on saquinavir plasma concentration is independent of
      ritonavir dosage: combined analysis of pharmacokinetic data from 97 subjects.
AB  - OBJECTIVE: To determine the correlation between ritonavir (RTV) dose and the
      degree of enhancement of saquinavir (SQV) exposure. METHODS: Combined analysis of
      pharmacokinetic data at steady state obtained from two open-label, randomized,
      parallel-group, multiple-dose, single-centre studies involving healthy
      volunteers. Plasma samples for SQV assay were obtained from 97 healthy subjects
      following multiple dosing of a range of SQV (400-1800 mg) plus RTV (100-400 mg)
      dosages for 13-14 days. The pharmacokinetics of SQV were derived by model
      independent, noncompartmental methods. Data were analysed by multivariate
      regression of log transformed Cmin and Cmax (geometric means) of SQV dosage as
      the dependent variable and independent variables of SQV and RTV dosage. Ritonavir
      was fitted as both a continuous and a categorical variable. RESULTS: There is a
      strong effect of any dose of RTV on Cmax and Cmin of SQV (P < 0.0001 for both
      parameters), but no greater effect of higher vs. lower RTV dosages on either
      parameter (Cmax: P=0.4373; Cmin: P=0.3393). Higher SQV dosage correlates linearly
      with higher Cmax (P=0.0093) and Cmin (P=0.0010), but the effects of increasing
      SQV dosages are less than with the addition of any RTV dose. CONCLUSIONS: RTV
      enhances SQV concentrations to increase Cmax and Cmin. This effect is similar for
      RTV dosages of 100-400 mg twice daily. Based on this concept of 'mini-dose' RTV,
      once-daily dosing of 1600 mg SQV/100 mg RTV and twice-daily 1000 mg SQV/100 mg
      RTV are currently being evaluated in clinical trials.

PMID- 12010357
TI  - Endogenous cytokine production protects T cells from spontaneous apoptosis during
      highly active antiretroviral therapy.
AB  - BACKGROUND: The availability of therapeutic regimens that effectively interfere
      with HIV-1 replication provides novel opportunities to investigate mechanisms of
      T-cell depletion as well as repopulation in infected individuals. METHODS:
      Nineteen HIV-1-infected individuals were investigated during one-year follow-up
      of highly active retroviral therapy (HAART). The frequencies of apoptotic T
      cells, as determined by propidium iodide, staining, TUNEL assay and analysis of
      annexin V, were assessed either in the absence or in the presence of anti
      interleukin (IL)2 and anti-IL-4 neutralizing Ab. Spontaneous and lectin-induced
      cytokine production were assessed by ELISA. RESULTS: Increments of both naive and
      memory CD4 and CD8 T cells during HAART are accompanied by a decrease of T-cell
      apoptosis that, after 12 months of HAART, reaches normal levels. This is
      associated with increments of both spontaneous and activation-induced production
      of IL-2 and IL-4 by peripheral blood mononuclear cells (PBMCs), though only the
      latter was found defective at enrolment. During HAART, blocking of either IL-2 or
      IL-4 production by PBMCs using neutralizing Ab restores levels of T-cell
      apoptosis consistent with those determined at enrolment. These data suggest that
      both IL-2 and IL-4 produced by PBMCs during HAART provide anti-apoptotic signals
      that can contribute to an increased survival of T cells and may thus play a part
      in long-term immune reconstitution. CONCLUSIONS: An effective viral suppression
      and, possibly, effects of PI on molecular targets other than viral components,
      can support a progressive normalization of T-cell survival that, at least in
      part, depends upon the restoration of proper soluble signals. These results
      provide evidence of a supporting role of endogenous cytokine production in
      peripheral T-cell repopulation during an effective and prolonged viral
      suppression. This may be relevant for the definition of immune-intervention
      targets aimed at immune reconstitution in HIV-1-infected patients.

PMID- 12010358
TI  - Impact of adherence on duration of virological suppression among patients
      receiving combination antiretroviral therapy.
AB  - OBJECTIVE: To assess the effect of adherence to antiretroviral therapy on the
      duration of virological suppression after controlling for whether or not the
      patient ever attained a plasma viral load below the limit of detection of
      sensitive HIV-1 RNA assays. METHODS: Data were combined from three randomized,
      blinded clinical trials (INCAS, AVANTI-2, and AVANTI-3) that compared the
      antiviral effects of two- and three-drug antiretroviral regimens. Virological
      suppression was defined as maintaining a plasma viral load below 1000 copies/mL.
      Adherence was defined prospectively and measured by patient self-report. RESULTS:
      Adherence did not have a major impact on the probability of achieving virological
      suppression for patients receiving dual therapy. However, for patients receiving
      triple therapy, adherence increased the probability of virological suppression,
      whether the plasma viral load nadir was above or below the lower limit of
      quantification. Compared to adherent patients with a plasma viral load nadir
      below the lower limit of quantification, the relative risk of virological failure
      was 3.0 for non-adherent patients with a nadir below the limit, 18.1 for adherent
      patients with a nadir above the limit, and 32.1 for non-adherent patients with a
      nadir above the limit. CONCLUSION: For patients receiving current three-drug
      antiretroviral regimens, adherence to therapy and plasma viral load nadir are
      important factors determining the duration of virological suppression.

PMID- 12010359
TI  - The relationship between ritonavir plasma trough concentration and virological
      and immunological response in HIV-infected children.
AB  - BACKGROUND: We studied a number of factors, including ritonavir plasma levels,
      and their capability of predicting response to therapy with ritonavir (RTV).
      METHODS: Eleven HIV-positive children, nucleoside reverse transcriptase inhibitor
      (NRTI)-experienced, protease inhibitor (PI) naive, receiving RTV in combination
      with two NRTIs were enrolled in the study. Demographic parameters were: median
      age (range) 10 (2-13) years, weight 26 (10-38) kg, body surface area (BSA) 0.93
      (0.47-1.21) m(2). Baseline values of CD4, percent CD4 and viral load were 137 (2
      1390) cells/microL, 9.5 (0.4-32.4)%, and 5.15 (4.30-6.18) log10 copies/mL,
      respectively. The dose of RTV was 318 (266-409) mg/m(2) twice daily. Peak (3.5 h
      after administration) and trough (predose) plasma concentrations of RTV were
      determined on one occasion at steady-state after a morning dose. Virological
      response to treatment was quantified as the difference between the baseline value
      of viral load and the value observed at 6 months of therapy (Delta(6)). RESULTS:
      The relationship between Delta(6) and demographic parameters (age, weight, BSA,
      and baseline CD4, percent CD4, and viral load) and plasma concentrations of RTV
      was studied by linear regression. Median (range) Delta(6) was 0.88 (0.77-2.62)
      log10 copies/mL. Peak and trough of RTV were 14.9 (3.2-31.4) and 5.0 (0.1-15.6)
      mg/L, respectively. Trough concentration of RTV was the best predictor of
      Delta(6), although the relationship between these two variables was not
      statistically significant (r = 0.56, P = 0.075). CONCLUSION: Our observation of a
      trend for a greater decrease in viral load in patients with higher trough
      concentration of RTV warrants further pharmacodynamic studies of PI in paediatric
      patients.

PMID- 12010360
TI  - The changing demographics of new HIV diagnoses at a London centre from 1994 to
      2000.
AB  - OBJECTIVE: To document the demographic changes in new HIV diagnoses at the Royal
      Free Hospital, London, UK, between 1994 and 2000. DESIGN: Retrospective case note
      review. METHODS: Data were extracted from the Royal Free HIV database identifying
      new diagnoses for 1994, 1997 and 2000. All case notes were reviewed and patients
      were included if they had their first positive HIV test at the Royal Free
      Hospital, or if they first tested positive elsewhere and attended the Royal Free
      HIV unit for their initial HIV care. Data extracted included sex, ethnicity, age,
      risk factor(s) for HIV, reason for test, clinical stage of disease, CD4 count and
      HIV RNA viral load at diagnosis. RESULTS: One hundred and forty-four patients
      were identified for 1994, 136 for 1997 and 110 for 2000. Over this time period
      the proportion of white patients dropped from 72% (n = 104) to 48% (n = 53), P =
      0.0001, whilst the proportion of black Africans rose from 24% (n = 34) to 45% (n
      = 49), P = 0.0004. The median CD4 count at diagnosis of the white cohort was 475
      cells/microL in 1994 and 286/microL in 2000, P = 0.005, whilst in the black
      African patients it was 240/microL and 230/microL for the same years.
      CONCLUSIONS: There has been a reduction in new HIV diagnoses among the white
      population and a rise in the black Africans at this centre between 1994 and 2000.
      The clinical and immunological parameters of HIV disease have worsened over this
      time period for the white group, but have remained stable in the black Africans.

PMID- 12010361
TI  - The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment
      response.
AB  - The M184V mutation in the HIV-1 reverse transcriptase gene is primarily
      associated with rapid, high-level lamivudine (3TC) resistance. It has also been
      observed to arise under selective pressure by abacavir, to which it confers low
      level resistance. Although the development of viral drug resistance remains a
      major concern in antiretroviral therapy, it is known that some immunological and
      clinical benefit can still be derived from highly active antiretroviral therapy
      (HAART) regimens despite resistance-associated virological failure. This residual
      benefit on a failing regimen is commonly attributed to the preservation of
      fitness-reducing protease inhibitor (PI) resistance mutations under continued
      drug pressure. However, fitness-reducing nucleoside reverse transcriptase
      inhibitor (NRTI) mutations may also contribute to the effect. M184V is both
      common in the treated population and fitness-reducing. A number of studies, both
      of dual nucleoside therapy and HAART, have noted a residual treatment effect for
      3TC despite the assumed or observed presence of M184V and high-level phenotypic
      resistance. The speed and consistency with which this mutation is selected by 3TC
      under suboptimal viral suppression therefore makes M184V a particularly
      interesting model for further clinical studies on the association of drug
      resistance with ongoing treatment benefit. While fitness considerations are
      likely to be a major contributor to the clinical observations noted, there are a
      number of other potential mechanisms that may contribute to a continuing response
      to 3TC in the presence of M184V. These include the delay and reversal of
      zidovudine (ZDV) resistance, hypersensitization to other NRTIs, reduced reverse
      transcriptase (RT) processivity and a possible reduction in RT
      pyrophosphorolysis. The full impact of M184V on therapeutic prospects will
      require further elucidation; ideally, the risk/benefit of preserving this
      substitution would be investigated in randomized trials. However, existing data
      suggest that the presence of this mutation may preserve some benefit in spite of
      the loss of 3TC susceptibility which, with further study, may prove valuable.

PMID- 12010362
TI  - Switch studies: a review.
AB  - Many physicians and patients wish to switch from successful protease inhibitor
      (PI)-based regimens to alternative regimens, usually composed of a nonnucleoside
      reverse transcriptase inhibitor (NNRTI) or abacavir plus two nucleoside reverse
      transcriptase inhibitors (NRTIs). This reflects a desire to avoid or reverse the
      metabolic changes observed during long-term PI-based antiretroviral therapy; to
      alleviate PI-associated adverse effects; and to improve adherence by simplifying
      the regimen. Data from a number of randomized and cohort PI switch studies are
      reviewed. Overall, the results of these studies are mixed, perhaps because of
      limitations in study design, patient number and duration of follow-up. In most
      studies, the frequency of virological failure is reduced by switching to a NNRTI
      regimen. Switching to an abacavir-based regimen is associated with two-fold
      higher risk of virological failure if mutations in the reverse transcriptase gene
      pre-exist. Improvements in metabolic and lipid abnormalities have not been
      uniform but favourable lipid changes have been reported, particularly after
      switching to nevirapine. Resolution of lipodystrophy symptoms has not been
      demonstrated objectively, perhaps because of insufficient follow-up and/or the
      role of NRTIs in this syndrome.

PMID- 12010363
TI  - Keratin expression in human tissues and neoplasms.
AB  - Keratin expression in human tissues and neoplasms Keratin filaments constitute
      type I and type II intermediate filaments (IFs), with at least 20 subtypes named
      keratin 1-20. Since certain keratin subtypes are only expressed in some normal
      human tissues but not others, and vice versa, various tissues have been
      subclassified according to the pattern of keratin staining. Simple epithelia
      generally express the simple epithelial keratins 7, 18, 19, and 20, while complex
      epithelia express complex epithelial keratins 5/6, 10, 14, and 15. When an
      epithelium undergoes malignant transformation, its keratin profile usually
      remains constant. The constitution and expression patterns of keratin filaments
      in human epithelial neoplasms are complex and often distinctive. In this article,
      we first briefly review the molecular and cell biology of keratin filaments. We
      then focus on the expression patterns of keratin filaments in various human
      neoplasms.

PMID- 12010364
TI  - Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and
      sialyl-Lewis(x) antigens in colorectal adenocarcinoma.
AB  - AIMS: The significance of MUC1, MUC2 and sialylated Lewis blood group antigens as
      prognostic markers in colorectal adenocarcinoma was investigated in a large
      series of patients because previous investigations revealed inconsistent results
      due to unrelated tumour samples from different patient groups and methodological
      differences. METHODS AND RESULTS: Tissues from 243 patients with colorectal
      adenocarcinoma were stained immunohistochemically. MUC1 showed a strong
      immunoreactivity (in more than 35% of the tumour area) in 32.5%, MUC2 in 51.0%,
      sialyl-Lewis(x) in 67.9% and sialyl-Lewis(a) in 73.7% of the cases, respectively.
      MUC1 immunoreactivity displayed a significant correlation with tumour progression
      as reflected by advancing pTNM staging and poor differentiation. MUC2 expression
      was significantly stronger in mucinous adenocarcinomas. Sialyl-Lewis(x)
      immunostaining correlated with the extent of lymph node metastasis as well as low
      cytological differentiation. According to univariate and multivariate analysis (P
      < 0.0001) only MUC1 reactivity represented a marker of worse survival
      probability, opposed to the sialylated Lewis antigens that did not exert a
      predictive value. CONCLUSIONS: According to our data, MUC1 and sialyl-Lewis(x)
      immunoreactivity exhibit statistically significant correlations with established
      markers of tumour progression. However, only MUC1 presents as an independent
      prognostic factor of colorectal adenocarcinoma.

PMID- 12010365
TI  - Expression of human mucin genes in normal kidney and renal cell carcinoma.
AB  - AIMS: Human mucins are large O-glycoproteins expressed by epithelial cells.
      Mucins are thought to be implicated in cell protection, cell adhesion and
      signalling. The aim of this study was to investigate the expression of the human
      mucin genes (MUC1-4, 5AC, 5B, 6-7) in normal kidney and renal cell carcinoma.
      METHODS AND RESULTS: We analysed by in-situ hybridization, immunohistochemistry
      and reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of
      these genes in normal adult kidney (n=14) and renal cell carcinomas (n=29). MUC1,
      MUC3 and MUC6 were expressed both in normal kidney and in renal carcinomas. In
      normal kidney, MUC1 was expressed in the distal convoluted tubules and in
      collecting ducts, whereas MUC3 was restricted to the proximal tubules. MUC4 was
      strongly expressed in epithelial urothelial cells of pyelocalyceal cavities. MUC6
      was only detected by RT-PCR. In renal carcinoma, we showed a heterogeneous
      expression of MUC1 and MUC3 with an over-expression of MUC3 in renal clear cell
      carcinoma. The level of MUC3 expression by in-situ hybridization was associated
      with the nuclear grade in clear cell carcinoma. CONCLUSIONS: This study is the
      first large series investigating human mucin gene expression in the kidney. MUC1,
      MUC3 and MUC6 are expressed in normal and tumour kidney. The over-expression of
      MUC3 in renal cell carcinomas favours its implication in renal tumorigenesis.

PMID- 12010366
TI  - The TSC-2 product tuberin is expressed in lymphangioleiomyomatosis and
      angiomyolipoma.
AB  - AIMS: Lymphangioleiomyomatosis is categorized by proliferation of abnormal smooth
      muscle cells (LAM cells) in the lungs and lymphatics and the presence of
      angiomyolipomas. Recently mutations in the tuberous sclerosis complex-2 gene (TSC
      2) have been described in LAM cells and angiomyolipomas. The TSC-2 protein
      tuberin is a tumour suppressor and its loss may result in cellular proliferation.
      We used immunohistochemistry to test the hypothesis that uncontrolled cellular
      proliferation in lymphangioleiomyomatosis is the result of reduced tuberin
      protein expression. METHODS AND RESULTS: Tissue from normal lung, normal kidney,
      lymphangioleiomyomatosis and angiomyolipomas was immunostained with three
      separate anti-tuberin antibodies. Tuberin staining in normal tissues was similar
      to that previously described. Surprisingly, tuberin was strongly expressed in the
      LAM cells of all cases of lymphangioleiomyomatosis and angiomyolipoma at a
      greater level than in normal smooth muscle cells. The perivascular cells of
      angiomyolipomas, however, did not stain for tuberin. CONCLUSIONS: Our results
      suggest that a loss of tuberin protein in LAM cells is not the cause of the
      cellular proliferation seen in lymphangioleiomyomatosis. Lymphangioleiomyomatosis
      may result either from the expression of a mutant tuberin with abnormal function,
      as a result of mutations in functionally related proteins, or from more than one
      mechanism.

PMID- 12010367
TI  - Differential Ki67 and bcl-2 immunoexpression in solid-glandular and spindle cell
      components of biphasic synovial sarcoma: a double immunostaining assessment with
      cytokeratin and vimentin.
AB  - AIMS: Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that
      may show a biphasic (spindle and solid/glandular components) or a monophasic
      histological appearance. In previous studies, we demonstrated that the
      solid/glandular component possesses higher proliferation rates than the spindle
      cell component of biphasic synovial sarcomas and that the spindle cell component
      may exhibit a progressive transition from or to the solid-glandular component in
      biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a
      novel approach to correlate immunoexpression of Ki67, bcl-2 and bax in the
      spindle cell and in the solid-glandular component of biphasic synovial sarcomas.
      We also performed a double-immunohistochemical assessment of the Ki67
      proliferative indices and the immunoexpression of anti-apoptotic protein bcl-2 in
      neoplastic cells expressing either vimentin or cytokeratin. METHODS AND RESULTS:
      Immunohistochemistry for vimentin (10 cases), bcl-2 (10 cases), Ki67(10 cases),
      cytokeratin (10 cases), and bax (eight cases), and double-immunostaining for
      vimentin/Ki67 (10 cases), vimentin/bcl-2 (nine cases), cytokeratin/Ki67 (10
      cases), and cytokeratin/bcl-2 (10 cases) assays were performed in 10 cases of
      primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for
      each case in both components. Statistical analysis was performed using Fisher's
      exact test or chi2 test. On conventional immunohistochemistry, the
      solid/glandular component revealed more expression of Ki67, bax and cytokeratin
      than the spindle cell component (P=0.0004, P=0.082, and P < 0.0001,
      respectively); on the other hand, the latter showed higher expression of bcl-2
      and vimentin than the former (P=0.0281 and P=0.059, respectively). Double
      immunohistochemistry analysis revealed higher co-expression levels of
      cytokeratin/Ki67 and cytokeratin/bcl-2 than the spindle cell component (P=0.015
      and P < 0.0001, respectively); conversely, the latter presented higher co
      expression of vimentin/bcl-2 than the former (P=0.0007). All cases showed no more
      than 10% of cells coexpressing cytokeratin/bcl-2, cytokeratin/Ki67, and no case
      revealed cells coexpressing vimentin/Ki67. CONCLUSION: Our findings indicate that
      in biphasic synovial sarcoma the acquisition of epithelial phenotype
      (solid/glandular component) is associated with a high expression of pro-apoptotic
      proteins and a high proliferative differentiation status, and conversely,
      mesenchymal phenotype (spindle cell component) is associated with a high
      expression of apoptosis-inhibitor bcl-2 and a low proliferative terminal-type
      differentiation status.

PMID- 12010368
TI  - Immunohistochemical localization of CEA, CA19-9 and DU-PAN-2 in hepatitis C virus
      infected liver tissues.
AB  - AIMS: We investigated expression of CEA, CA19-9 and DU-PAN-2 in liver tissues of
      chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, measuring their
      serum value to clarify their clinical significance, and proliferating cell
      nuclear antigen (PCNA) was assessed in serial sections to determine whether
      expression of these molecules in chronic liver disease was related to
      regeneration of biliary ducts. METHODS AND RESULTS: Liver tissues were biopsied
      under peritoneoscopy or echo-guidance and resected surgically among 63 patients
      with anti-hepatitis C virus-positive sera. There were 26 cases of chronic
      hepatitis, 21 cases of liver cirrhosis and 16 cases of hepatocellular carcinoma
      (four cases of mixed type). They were simultaneously used for immunocytochemistry
      for CEA, CA19-9 and DU-PAN-2, and PCNA was demonstrated in serial liver tissues
      by immunohistochemistry. Serum CEA, CA19-9 and DU-PAN-2 were measured by
      radioimmunoassay or enzyme immunoassay. In chronic hepatitis and liver cirrhosis
      CEA immunoreactivity was seen on membranes facing bile canaliculi and in bile
      ductules. Both CA19-9 and DU-PAN-2 immunoreactivity were observed in bile
      ductules in chronic hepatitis liver cirrhosis and non-neoplastic areas
      surrounding hepatocellular carcinoma, and CA19-9 was also present in interlobular
      bile ducts. PCNA immunoreactivity was not detected in marker-positive bile
      ductules or interlobular bile ducts. In hepatocellular carcinoma CEA
      immunoreactivity was seen on membrane facing dilated bile canaliculi in glandular
      structures, and CEA, CA19-9 and DU-PAN-2 immunoreactivity was observed in
      cholangiolar areas in mixed type of hepatocellular carcinoma. CONCLUSIONS: CEA in
      chronic hepatitis and liver cirrhosis is expressed not only in bile ductules but
      also on membrane facing bile canaliculi, and both CA19-9 and DU-PAN-2 were seen
      in different levels of biliary ducts. These molecules were expressed in bile
      ductules in surrounding non-neoplastic areas of hepatocellular carcinoma, and
      their expression was not associated with regeneration of biliary ducts. CEA
      expression was present in the trabecular type of hepatocellular carcinoma, and
      CA19-9 and DU-PAN-2 were observed in cholangiolar areas in mixed type of
      hepatocellular carcinoma.

PMID- 12010369
TI  - Cytokeratin expression in gastrointestinal stromal tumours: a word of caution.

PMID- 12010370
TI  - Ki67 protein: the immaculate deception?

PMID- 12010371
TI  - Epithelioid microgranulomas after Pentostatin therapy in hairy cell leukaemia.

PMID- 12010372
TI  - Undifferentiated small cell hepatoblastoma with a chromosomal translocation
      t(22;22)(q11;q13).

PMID- 12010373
TI  - Lipomatous pleomorphic adenoma of parotid gland.

PMID- 12010374
TI  - Papillary and cystic insulinoma of the pancreas.

PMID- 12010375
TI  - Hepatocellular carcinoma in primary biliary cirrhosis: case reports and review of
      the literature.

PMID- 12010376
TI  - A comparison of basal cell markers used in the prostate.

PMID- 12010379
TI  - Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios
      in women with menstrual migraine.
AB  - OBJECTIVE: It has been suggested that magnesium deficiency may play an important
      role in menstrual migraine and that the serum ionized calcium (ICa2+)/ionized
      magnesium (IMg2+) ratio is important in migraine headache. Studies were designed
      to test these hypotheses. DESIGN: We prospectively evaluated 270 women seen at a
      headache clinic and in 61 women with menstrual migraine measured IMg2+, total
      magnesium, and ICa2+ levels so as to calculate the ICa2+/IMg2+ ratio. RESULTS:
      The incidences of IMg2+ deficiency were 45% during menstrual attacks, 15% during
      nonmenstrual attacks, 14% during menstruation without a migraine, and 15% between
      menstruations and between migraine attacks. The serum ICa2+ levels were within
      our reference range, but the ICa2+/IMg2+ ratio was elevated (P<.01) in menstrual
      migraine. CONCLUSIONS: The high incidence of IMg2+ deficiency and the elevated
      ICa2+/IMg2+ ratio during menstrual migraine confirm previous suggestions of a
      possible role for magnesium deficiency in the development of menstrual migraine.

PMID- 12010380
TI  - Mouth-dispersible aspirin in the treatment of migraine: a placebo-controlled
      study.
AB  - OBJECTIVE: To compare the efficacy of mouth-dispersible aspirin 900 mg and
      placebo in the treatment of migraine. BACKGROUND: Aspirin is widely accepted as
      an effective therapy for migraine. Previous studies have indicated that gastric
      stasis and delayed gastric emptying, which occur during migraine attacks, delay
      aspirin absorption. Mouth-dispersible formulations are considered to be more
      quickly absorbed than solid formulations and, therefore, may be more effective in
      treating migraine. DESIGN: Randomized, double-blind, placebo-controlled,
      crossover study in four specialized migraine clinics in the United Kingdom.
      METHODS: One hundred one patients diagnosed with migraine (according to the
      International Headache Society diagnostic criteria) participated in the study.
      Patients received either single doses of mouth-dispersible aspirin (3 x 300 mg)
      or placebo for moderate pain in the treatment of two migraine attacks. Rescue
      medication could be taken after 2 hours, if required. The primary efficacy
      parameter was response to therapy at 2 hours posttreatment. Other efficacy
      parameters were response to treatment, pain-free, and pain intensity at all other
      time points. Functional disability, nausea, vomiting, photophobia, phonophobia,
      symptom relief, patient and investigator global evaluation, use of rescue
      medication, headache recurrence, and palatability and convenience were also
      recorded. RESULTS: Of 101 patients, 73 took both treatments. At 2 hours, 48% of
      patients taking mouth-dispersible aspirin responded, compared to only 19% taking
      placebo (P =.0005). Mouth-dispersible aspirin was significantly better than
      placebo for response to treatment (P<.05) and pain intensity difference (P<.01)
      at all time points from 30 minutes posttreatment; for pain-free (P<.05) and use
      of rescue medication (P<.01) from 3 hours posttreatment; for headache recurrence
      (P<.05); and for patients' and investigators' global evaluations of efficacy (P
      =.0001 in both cases). CONCLUSIONS: Mouth-dispersible aspirin 900 mg is effective
      compared with placebo for the treatment of moderate migraine head pain, with
      relief seen from as early as 30 minutes after taking medication.

PMID- 12010381
TI  - Headaches associated with refractive errors: myth or reality?
AB  - INTRODUCTION: Headache and refractive errors are very common conditions in the
      general population, and those with headache often attribute their pain to a
      visual problem. The International Headache Society (IHS) criteria for the
      classification of headache includes an entity of headache associated with
      refractive errors (HARE), but indicates that its importance is widely
      overestimated. OBJECTIVES: To compare overall headache frequency and HARE
      frequency in healthy subjects with uncorrected or miscorrected refractive errors
      and a control group. METHODS: We interviewed 105 individuals with uncorrected
      refractive errors and a control group of 71 subjects (with properly corrected or
      without refractive errors) regarding their headache history. We compared the
      occurrence of headache and its diagnosis in both groups and assessed its relation
      to their habits of visual effort and type of refractive errors. RESULTS: Headache
      frequency was similar in both subjects and controls. Headache associated with
      refractive errors was the only headache type significantly more common in
      subjects with refractive errors than in controls (6.7% versus 0%). It was
      associated with hyperopia and was unrelated to visual effort or to the severity
      of visual error. With adequate correction, 72.5% of the subjects with headache
      and refractive error reported improvement in their headaches, and 38% had
      complete remission of headache. Regardless of the type of headache present,
      headache frequency was significantly reduced in these subjects (t = 2.34, P
      =.02). CONCLUSIONS: Headache associated with refractive errors was rarely
      identified in individuals with refractive errors. In those with chronic headache,
      proper correction of refractive errors significantly improved headache complaints
      and did so primarily by decreasing the frequency of headache episodes.

PMID- 12010382
TI  - Migraine is associated with livedo reticularis: a prospective study.
AB  - OBJECTIVE: To investigate the relationship of livedo reticularis, an ischemic
      dermatopathy, and migraine, an ischemic stroke risk factor. BACKGROUND: Livedo
      reticularis refers to the reddish-blue reticular mottling of the skin resulting
      from narrowing of small and medium arteries at the dermis-subcutis border. A
      subset of patients with livedo reticularis develop stroke in the absence of other
      vascular risk factors, which has been termed Sneddon syndrome. We undertook this
      prospective study in a non-neurology clinic to delineate further the relationship
      of livedo reticularis and migraine. METHODS: Patients in a general dermatology
      clinic were interviewed for vascular risk factors and history of migraine in
      accordance with the International Headache Society (IHS) criteria. A
      dermatologist, not familiar with the interview, recorded the primary
      dermatological diagnosis and the presence or absence of livedo reticularis on
      examination. RESULTS: Two hundred eighty-one consecutive patients (184 women and
      97 men; average age, 52 years) were interviewed and examined. Seventy-five (27%)
      had migraine (IHS codes 1.1, 1.2) and an additional 18 (6%) had atypical migraine
      (IHS 1.7). Livedo reticularis was noted in 46 patients (16%), with the frequency
      higher in women than men (42 [23%] of 184 versus 4 [4%] of 97; P <.0001). The
      frequency of livedo reticularis in patients with migraine was higher than in
      those without migraine (24 [26%] of 93 versus 22 [12%] of 188; P =.002), and
      higher in female than male migraineurs (23 [32%] of 72 versus 1 [5%] of 21; P
      =.012). In logistic regression analysis of the women, migraine was associated
      with livedo reticularis (odds ratio [OR], 2.3; confidence interval [CI], 1.08 to
      4.71), as well as with stroke (OR, 4.0; CI, 0.87 to 18.21), coronary artery
      disease (OR, 3.5; CI, 1.16 to 10.33), and deep venous thrombosis (OR, 3.2; CI,
      0.98 to 10.32). CONCLUSIONS: In women, migraine is associated with stroke,
      coronary artery disease, deep venous thrombosis, as well as livedo reticularis, a
      dermatopathy which has been pathologically linked to cerebral vasculopathy.
      Whether migraineurs with livedo reticularis compose a subset at higher risk of
      thrombosis, including stroke, deserves further investigation.

PMID- 12010383
TI  - Quality of life in young Italian patients with primary headache.
AB  - OBJECTIVE: To compare the quality of life of young Italian patients with headache
      with that of the juvenile Italian population free of chronic disease. METHODS:
      The Quality of Life Headache in Youth (QLH-Y) Questionnaire developed by Dutch
      investigators was translated into Italian and validated in a young Italian
      population. The forward/backward translation and, for psychometric testing, the
      factor analysis and Cronbach coefficient alpha were used. A new instrument
      (Questionnaire for Young Subjects Affected by Primary Headache) was developed to
      assess psychological, physical, and social functioning and functional status and
      was used to compare the quality of life of the patients with headache with that
      of headache-free controls. For psychometric testing (via the questionnaire), we
      selected a sample of 394 subjects (178 males and 216 females, aged 10 to 18
      years): 320 subjects from three schools of North Italy and 74 patients with
      headache from the Paediatric Headache Center of Padua. In the latter group, 48
      patients had tension-type headache and 26 had migraine without aura, according to
      the International Headache Society diagnostic criteria. RESULTS: The data derived
      from the comparison of 84 headache-free subjects (control group) and the 74 young
      patients with headache confirmed that primary headache negatively influenced the
      latter's quality of life: patients scored significantly (P<.05) lower on
      psychological, physical, and social functioning than the headache-free controls.
      CONCLUSIONS: Quality of life is compromised significantly in young patients with
      primary headache disorders. The questionnaire used in this study is a valid and
      reliable self-administered instrument that may facilitate clinical research in
      headache.

PMID- 12010384
TI  - Epidemiological and clinical characteristics of migraine in Sivas, Turkey.
AB  - OBJECTIVE: To investigate the epidemiology of migraine in Sivas, Turkey,
      including its prevalence, clinical characteristics, and impact according to age,
      sex, and socioeconomic status. METHODS: Thirteen hundred twenty subjects were
      personally interviewed by a neurologist. Each household member with headache was
      asked questions regarding their headaches including age at onset, frequency,
      duration, character, location, severity, aggravating and ameliorating factors,
      and prodromal and associated symptoms. Migraine diagnoses were determined in
      accordance with the classification criteria of the International Headache
      Society. RESULTS: Migraine was identified in 173 subjects (45 males and 128
      females), and lifetime prevalence of migraine was 7.9% (95% CI, 5.66 to 10.1) in
      males and 17.1% (95% CI, 14 to 20) in females. Aura was reported by 1.4% of males
      and 3.3% of females. CONCLUSION: Migraine prevalence in Turkey is similar to that
      reported in Europe and the United States.

PMID- 12010385
TI  - Headache syndromes amongst schoolchildren in Riyadh, Saudi Arabia.
AB  - We evaluated 1,400 randomly selected Saudi children in grades 1 through 9 to
      determine the prevalence of migraine and tension-type headache. Of the 1400
      distributed questionnaires, 1,181 (84.3%) were completed properly and so served
      as the basis for analysis. There were 573 boys (48.5%) and 608 girls (51.5%).
      Ages ranged from 6 to 18 years. Five hundred eighty-eight children (49.8%; 272
      boys and 316 girls) had recurrent headache episodes not related to febrile
      illness in the year preceding the survey. Eighty-four children (7.1%; 37 boys and
      47 girls) had recurrent episodes of migraine, and 504 (42.7%; 232 boys and 272
      girls) had recurrent episodes of nonmigraine headache. For both boys and girls,
      the age-specific prevalence rate for nonmigraine headache rose steadily from
      around 15% at aged 6 to 7 years to nearly 60% after aged 15. For migraine, there
      was a sharp increase in the prevalence rate (from around 2% to around 9%) at aged
      10 to 11, also in both boys and girls. Age-adjusted prevalence for migraine
      between aged 6 and 15 was 6.2%. Due to the relatively poor sensitivity of some of
      the IHS criteria in children, this figure may underestimate the true magnitude of
      migraine in the population studied.

PMID- 12010386
TI  - Prevalences of migraine and tension-type headache in adolescent girls of Shiraz
      (southern Iran).
AB  - OBJECTIVE: To determine the prevalences of migraine and tension-type headache in
      teenaged girls attending schools in Shiraz (southern Iran). BACKGROUND: Studies
      of headache prevalence are numerous, and findings have varied according to the
      specific population and region involved. No data are available regarding headache
      prevalence among Iranian teenagers. METHODS: A random sample of 1868 teenaged
      girls (aged 11 to 18 years) was evaluated, and 507 subjects reported headache.
      The headache disorders were classified on the basis of a clinical interview,
      general physical and neurologic examinations, and the diagnostic criteria of the
      International Headache Society. Logistic regression was used for data analysis.
      RESULTS: Overall prevalence rate for migraine was 6.1% (95% CI, 5.0 to 7.2) and
      for tension-type headache, 12.1% (95% CI, 10.6 to 13.6). Migraine and tension
      type headache were significantly associated. CONCLUSIONS: It is concluded that
      exposition of subjects to sunlight, type of food, and a family history of
      headache had most significant effects on occurrence of migraine and tension-type
      headaches.

PMID- 12010387
TI  - Cryptic pituitary hemorrhage presenting with headache.
AB  - We report a case of pituitary hemorrhage and review the literature on that
      condition. Our patient presented with a sudden bifrontal headache associated with
      vague transient visual blurring but without nausea or other associated symptoms.
      After a negative workup at another hospital, including an unremarkable brain
      computed tomography without contrast, and resolution of headache following
      treatment with injectable sumatriptan, he was diagnosed with "atypical migraine."
      The patient's symptoms soon returned, and brain magnetic resonance imaging
      revealed an enlarged, cystic pituitary gland with a small intraparenchymal
      hemorrhage.

PMID- 12010388
TI  - Diffusion-weighted magnetic resonance imaging during the aura of pseudomigraine
      with temporary neurologic symptoms and lymphocytic pleocytosis.
AB  - A typical feature of pseudomigraine with temporary neurologic symptoms and
      lymphocytic pleocytosis (PMP) is the long duration of aura symptoms. To determine
      if these prolonged auras cause early ischemic parenchymal changes, we performed
      diffusion-weighted magnetic resonance imaging during the aura of a patient with
      PMP and found no reduction of water diffusion.

PMID- 12010389
TI  - Headache associated with postpartum cerebral angiopathy: monitoring with
      transcranial color-coded sonography.
AB  - We report a case of postpartum cerebral angiopathy with headache; a rare entity
      that affects women within the early postpartum period. Cerebral angiography
      revealed multiple segmental narrowings of major cerebral arteries. The patient
      was monitored with transcranial color-coded sonography of the middle cerebral
      artery. Abnormally increased flow velocity within the middle cerebral artery
      decreased following initiation of steroid therapy, and the patient's headache
      improved dramatically.

PMID- 12010390
TI  - Valsalva-induced cluster: a new subtype of cluster headache.
AB  - We report the case of a man who suffered from Valsalva-induced cluster headaches.
      The headaches deviated from classic cluster in that they were solely induced by
      activity involving the Valsalva maneuver, such as coughing and sneezing, and
      never occurred spontaneously. The attacks were prevented by treatment with
      indomethacin. This may be the first reported case of cluster that only occurs
      after a defined trigger and never spontaneously. It also may be the first cluster
      headache subtype that is indomethacin responsive.

PMID- 12010391
TI  - Serum glucose regulation and headache.

PMID- 12010392
TI  - Thunderclap headache.

PMID- 12010393
TI  - Tuberous sclerosis and a not so benign astrocytoma.

PMID- 12010394
TI  - Stabbing headache in a teenager.

PMID- 12010395
TI  - Headache and acute coronary syndromes.

PMID- 12010397
TI  - Migraine, Midrin, and Imitrex.

PMID- 12010399
TI  - Mixing sumatriptan.

PMID- 12010400
TI  - Flurries of migraine (with) aura and migraine aura status.

PMID- 12010401
TI  - Propofol in the treatment of presurgical headache and nausea.

PMID- 12010402
TI  - Extended-release divalproex sodium improves the quality of life of adolescent
      migraineurs.

PMID- 12010404
TI  - Concentrate safety and efficacy.
AB  - Safety from transmission of infections through plasma-derived clotting factor
      concentrates is assured by improved donor screening, serological testing of
      individual donations and direct viral testing of small plasma pools. Modern viral
      inactivation techniques are highly effective. Recombinant concentrates stabilized
      in human albumin are being superaeded by those with other stabilizers. Recently
      reported discrepancies between estimates of concentrate potency from in vitro
      assays versus in vivo recovery, depending upon type of assay and reference
      standard used, are not fully resolved.

PMID- 12010405
TI  - Conduct of clinical trials in developing countries.
AB  - Research subjects in developing countries may be especially vulnerable to
      exploitation. Scrupulous care should be taken to maintain the basic principles of
      ethical trial conduct: the right of participants to make their own informed
      decisions, a favorable balance of benefit to risk, good trial design, candour
      about results, and, above all, use of honourable investigators. Involvement of
      local participants in planning a trial helps ensure both culturally-sensitive
      protocols and consents and also maximum benefit to patients and to local research
      infrastructure.

PMID- 12010406
TI  - Continuous infusion of coagulation factors.
AB  - Continuous infusion (CI) of coagulation factor concentrate is aimed at
      maintaining a steady haemostatic level of the missing factor in circulation,
      preventing dangerous troughs below the haemostatic level and unnecessary high
      peaks, which increase the safety and decrease the consumption of factor
      concentrate replacement therapy. This can be achieved by the administration of
      the coagulation factor at a rate corresponding to its elimination. CI has been
      used in wider extent since the early 1990s, after the resolution of basic
      questions such as the stability of factor concentrates after reconstitution, the
      risk of contamination and bacterial overgrowth in these biological materials
      during either preparation of infusion bags or prolonged administration, the
      frequent local thrombophlebitis, the knowledge of pharmacokinetics of coagulation
      factors in the conditions of CI and the development of adequate minipumps. The
      increasing clinical experience with CI used in haemophilia A and B and von
      Willebrand disease has proven the advantages of this mode of replacement therapy,
      providing improved margins of efficacy and safety in various clinical settings
      requiring the maintenance of haemostatic levels over prolonged periods, as well
      as reduction in treatment cost compared with the traditional therapy via
      intermittent injections of coagulation factors. KEYWORDS: continuous infusion,
      factor VIII, factor IX, haemophilia, recombinant FVIIIa, von willebrand disease.

PMID- 12010407
TI  - Paediatric care of the child with haemophilia.
AB  - The paediatric care of children with haemophilia in developed countries should
      focus on the health of the child, not on the disorder. Gene therapy offers the
      hope of an ultimate 'cure' for the disorder, but until this is a viable
      proposition, patients should be given more control over their treatment, and the
      focus should be on 'self-monitored and self-adjusted' prophylaxis. New
      instruments for measuring joint function and radiographic changes, and quality of
      life are valuable tools in improving the treatment of paediatric care for
      children with haemophilia.

PMID- 12010408
TI  - Prophylaxis in developed and in emerging countries.
AB  - The significant progress made in recent years in the safety and efficacy of both
      plasma-derived and recombinant factor concentrates has allowed treatment
      programmes to be developed that go beyond the simply curative or the treatment of
      the consequences of the disease (episodic or on-demand treatment), enabling the
      criteria of preventative medicine to be applied to congenital bleeding disorders.
      The aim of these programmes is to achieve constant, minimum levels of factor in
      patients above 1 or 2%, thereby converting severe haemophilia into moderate
      haemophilia.

PMID- 12010409
TI  - The use of haemostatic drugs in haemophilia: desmopressin and antifibrinolytic
      agents.
AB  - Over the last 4 decades, there have been very significant advances in the
      treatment of haemophilia. Plasma products first became available in the 1960s,
      beginning with cryoprecipitate and then intermediate-purity plasma concentrates,
      for the treatment of haemophilia A and B. The disasters of viral infections
      amongst people with haemophilia in the 1980s served to stimulate both the
      development of techniques of viral inactivation of concentrates and the
      manufacture of purer products. We therefore now have safe plasma products that
      are also pure in that they are concentrates of only the deficient protein
      responsible for the congenital coagulopathy. Preparations of specific coagulation
      proteins obtained using recombinant biotechnology techniques have been available
      since 1995. By contrast, pharmacological options for the treatment of the
      haemophilia remain very limited. The only therapeutic alternatives of real
      practical value which have been available in the last 30 years for the treatment
      of haemophilic patients are desmopressin, antifibrinolytic agents, aprotinin,
      concentrated oestrogens, and local haemostatic agents such as topical thrombin or
      fibrin glue. This article aims to assess the pharmacological basis and
      accumulated experience relating to these drugs when used for the prevention and
      treatment of bleeding in patients with haemorrhagic disorders.

PMID- 12010410
TI  - Orphan drugs: legal aspects, current situation.
AB  - 'Rare disorders' is the name given to those diseases, of very varied aetiology,
      whose common denominator is that they are low-prevalence diseases, and for the
      majority of which there is no treatment available. The World Health Organization
      defines a rare disorder as all pathological conditions affecting 0.65-1 out of
      every 1000 inhabitants. The European Union understands a rare disorder to be one
      with a prevalence of 5 : 10 000 Europeans; the USA defines it as an ailment
      affecting fewer than 200 000 Americans; Japan sets the limit at 50 000 Japanese
      patients; Australia at 2000 Australian patients. According to the aforementioned
      ratios, haemophilia, von Willebrand disease and other congenital coagulation
      disorders could be considered to be rare disorders. 'Orphan drugs' is the term
      given to those drugs intended for the treatment of rare disorders, because the
      number of patients affected is so small that it is not profitable to invest in
      research and development or to market them. Although the ratio of people affected
      by haemophilia means it could be classed as a rare disorder and its treatment
      could therefore be given orphan designation, haemophilia does have an established
      treatment, and research and development in this area proves profitable for the
      pharmaceutical companies. Haemophilia is therefore singular in that
      pharmaceutical companies can file an application for orphan designation with all
      the benefits deriving from this, while the treatment of haemophilia is profitable
      in its own right for companies carrying out research and development for the
      products involved.

PMID- 12010411
TI  - Haemophilia in the developing world: the Brazilian experience.
AB  - The success of haemophilia treatment is based on well-established criteria, and
      the use of clotting factor concentrates is fundamental. These strategies are seen
      in the developed world when measures of quality of life are studied or when
      disabilities are evaluated among haemophilic patients. At the same time,
      countries in the developing world, with almost 80% of the haemophilia population,
      are making tremendous efforts to change their diagnosis and treatment methods, in
      order to improve their healthcare and therefore be able to promote better life
      for haemophiliacs. However, these goals are threatened when there are many social
      needs and few economic resources. There is wide variation in conditions in these
      countries, depending on what has already been done, how many patients the country
      has, how the blood banking services are planned and obviously, what are the
      interested parties. Even with so many difficulties, there are ways to work
      towards and reach the most important goal, which is to prepare the haemophiliacs
      to be citizens that are as productive and capable of working as are the
      nonhaemophiliacs. Each country has to take its part; the commitment of the
      community, physicians and government will be needed to design a model that is
      compatible with all the necessities and possibilities, and is understood by all
      the persons involved.

PMID- 12010412
TI  - Haemophilia care in the developing world: benchmarking for excellence.
AB  - Seventy-five percent of patients with haemophilia receive no or inadequate
      treatment, and often do not survive to adulthood. With efficient organization,
      the disorder is treatable and becomes part of normal life. In developing
      countries there is a large discrepancy in haemophilia care. Some have zero
      treatment levels, while others already have comprehensive care centres. This
      paper attempts to assess and standardize the levels of haemophilia care for
      developing countries, setting up benchmarks or guidelines for future development.
      Four major areas are emphasized: clinical care, laboratory, blood products and
      patient organization. For each country or community, development work begins
      after the assessment of competency level in each area. The next step is then to
      plan, organize, improve and move up to the next level. To become successful, a
      sound and realistic strategy should be employed, starting from the identification
      of key leaders and the recruitment of an expert team. To obtain recognition and
      support from health authorities, the haemophilia care programme should not limit
      itself to haemophilia care but should also include medical care for all bleeding
      disorders, including the improvement of blood banks, blood products, coagulation
      laboratories and other medical facilities. This would directly improve the
      overall medical care standard of the whole hospital. It is also important to
      emphasize the need for selfreliance, employing simple yet effective methodology,
      equipment and mechanical facilities. The effective coordination of World
      Federation of Hemophilia assistance and the host country's committed action will
      ensure success in the emerging trend of better haemophilia care in developing
      countries.

PMID- 12010413
TI  - Quality management and quality assurance in haemophilia care: a model at the Bonn
      haemophilia centre.
AB  - The severe clotting defects associated with the diagnosis of severe haemophilia A
      and B require a quality management and quality assurance system designed to avoid
      both bleeding sequelae (such as damaged joints) through early on-demand or
      prophylactic treatment in a home-care setting, and side-effects such as
      infectious diseases (hepatitis A-G and human immunodeficiency virus), allergic
      reactions, haemolysis and if possible inhibitor formation, by using highly
      purified, virus-inactivated or recombinant products in which the factor VIII and
      IX proteins are as natural as possible. As the intravenous injection of the
      required clotting factor is entrusted to the patients in home treatment, the
      haemophilia centre has to check treatment protocols and, when necessary, joint
      and muscle status. In addition, it is imperative to ensure the safety of the
      product, and checks must be carried out to make sure that batch numbers are
      recalled as soon as possible if side-effects are observed. These are the reasons
      for several Acts of Parliament in Germany requiring special treatments and
      regular checks (the Disabled Act, recommendations by the German Medical Council,
      the Transfusion Act). Thus, at the haemophilia centre in Bonn we have established
      a special quality management and quality assurance system taking into account the
      great number of patients (> 800), the often considerable distance between the
      centre and the patient, and the aforementioned regulations and laws. Quality
      management involves dealing with daily practicalities such as 24-h availability
      of a physician, medical technologist and nurse, careful instruction of patient
      and family in home care, genetic counselling, regular laboratory tests
      (especially recovery time, half-life, inhibitors and gene defects, clinical
      chemistry and serology) and clinical investigations (especially joint and muscle
      status). It also includes co-operation with family doctors and different
      departments at our university hospital (e.g. orthopaedic, microbiology), daily
      conferences with staff, information for nursery schools, schools, training
      institutions and/or the workplace in case of emergency, and cooperation with
      German haemophilia foundations. For quality assurance, several self-controlling
      systems are in place, such as distribution of concentrate, laboratory data,
      treatment protocols, joint and muscle status and bleeding tendencies. All these
      and more are double-checked and interactive, controlling data and activities with
      the help of EDP. Exceptional staff motivation and patient compliance are
      important for this quality system.

PMID- 12010414
TI  - Linking medicine and economics: health economics and quality of life in
      haemophilia care.
AB  - Scarce resources in healthcare are a fact of life everywhere. Providing optimal
      healthcare for haemophilia means delivering the best possible clinical outcomes
      at an acceptable total cost, however that is defined by individual societies.
      Health economics helps us to do this. So far, economic evaluation has enhanced
      our understanding of some of the economic implications of haemophilia and has
      provided some guidance on the way forward to optimize efficient allocation of
      resources for this condition. Further advances and consensus on evaluation
      methods and standards for the economics of haemophilia are required, however.
      This need will continue in the face of new, more sophisticated and therefore more
      costly haemophilia therapies.

PMID- 12010415
TI  - Haemophilia 2002: emerging risks of treatment.
AB  - Haemophilia care and treatment products have greatly improved over the past 2
      decades. Transitions in treatment produced by these changes were accompanied by
      the emergence of unexpected risks and new complications. In order to provide the
      best comprehensive care to patients with haemophilia, healthcare providers
      periodically need to re-evaluate and adjust their management and therapeutic
      products to prevent or minimize the effects produced by the emerging issues. For
      example, reducing the effects of infectious agents remains the highest priority
      for the haemophilia community because of the high level of morbidity and
      mortality that has resulted from earlier therapeutic agents. In many countries,
      the goal has been to achieve absolute zero risk for infectious agents. In some
      instances, the screening procedures to achieve these goals reduced the
      availability of plasma needed for manufactured derivatives and produced another
      emerging risk, shortages of clotting factor preparations. Similarly, better
      diagnostic methods identified other potential agents that were not inactivated by
      current technology. Likewise, immune tolerance regimens and the prophylactic
      management of haemophilia introduced different therapeutic delivery systems with
      their own risks. The drugs used to manage diseases such as human immunodeficiency
      virus (HIV), which were transmitted by products manufactured before mid-1980,
      create their own set of risks for this community. Topical emerging risks of
      treatment, including variant Creutzfeldt-Jakob disease, an assessment of its
      risks and impact, the complications of using indwelling catheters, and the role
      of protease inhibitors used to treat HIV may have on bleeding complications of
      haemophilia are discussed.

PMID- 12010416
TI  - Risk of variant Creuzfeldt-Jakob disease from factor concentrates: current
      perspectives.
AB  - The demonstration of iatrogenic transmission of Creuzfeldt-Jakob disease (CJD)
      through therapeutic interventions led to substantial concerns in communities
      requiring blood products in the 1980s and 1990s. These concerns led some
      regulatory authorities to adopt a very precautionary approach and require recall
      of plasma products, including factor concentrates, which included donors at risk
      of CJD. The FDA's approach on recall contributed to a substantial lack of plasma
      products on the world market in the mid- to late 1990s. Growing epidemiological
      evidence of non-transmission of CJD to humans through blood, as well as
      demonstration of the plasma fractionation system's ability to eliminate CJD-type
      agents, led the FDA to rescind its measures for product recall in 1998. Although
      no evidence exists that the variant strain of CJD (vCJD) will behave any
      differently to the classic strain (cCJD) of the disease during fractionation,
      indications that higher levels of the strain may be present in the blood in vCJD,
      as well as the uncertainty regarding the epidemiology of the disease, has led to
      a new round of precautionary measures aimed at minimizing vCJD risk. Currently,
      the traditional approach to product safety through appropriate donor selection,
      screening using laboratory tests and systematic pathogen elimination is not
      completely possible for addressing the risk of vCJD. The only definite risk
      factor for vCJD is residence in a country where meat products from cattle with
      bovine spongiform encephalopathy (BSE) have been consumed; currently this is
      predominantly the United Kingdom but the appearance of BSE in other European
      countries has stimulated non-European regulatory authorities to defer blood
      donors from most of Europe. There is currently no screening test available for
      vCJD. Plasma fractionation techniques fortuitously appear to eliminate
      substantial amounts of vCJD like agents but only one pathogen eliminating
      technique, nanofiltration, has been proposed for specifically eliminating vCJD
      like agents. Despite the current uncertainty, it is possible to be cautiously
      optimistic regarding the safety of factor concentrates from the risk of vCJD. An
      accumulating body of evidence suggests that it is unlikely that the plasma pool
      from countries with moderate BSE epidemics will contain sufficient levels of vCJD
      agent to lead to an infective final product. Nevertheless, the development of a
      blood screening test and more dedicated elimination methods are high priorities
      for the blood industry as it faces this new threat. The community of blood
      product users, including people with haemophilia, need to be in a position to
      make an informed choice regarding the risk of this new agent. Such a choice needs
      to take into account the alternatives to plasma product therapy such as
      recombinant concentrates and the risks to product supply ensuing from an
      excessive reliance on one form of product.

PMID- 12010417
TI  - Evolving perspectives in product safety for haemophilia.
AB  - The past decade has seen a consolidation of the safety measures built into the
      manufacture of coagulation factor concentrates for people with haemophilia. The
      scientific developments of the 1980s have been fully reflected in the
      manufacturing principles and the regulatory control of concentrate production, so
      that the safety of concentrate therapy now exceeds the safety of normal blood
      transfusion. A clear understanding of the epidemiology of the transfusion
      transmitted viruses allows the selection of donors with a satisfactory safety
      profile. Source material for plasma-derived concentrates is now screened with
      sensitive tests that detect viral infection in donors at a very early phase in
      the viral life cycle. This decreases the potential viral load to levels that are
      easily eliminated by well-accredited viral inactivation procedures. These
      measures have ensured a high level of assurance regarding the safety of products
      from the traditional transfusion-transmitted infections. However, testing for
      some transfusion-transmitted viruses does not yet form part of mainstream blood
      screening; alternative strategies based upon the particular needs of pooled
      plasma product recipients may be more feasible. Whereas the risk of emerging
      pathogens has to be kept constantly under review, four such viruses identified
      over the 1990s have proven to be of little relevance to plasma product recipients
      and the need for measures specifically directed against them is debatable. The
      risk of variant Creuzfeldt-Jakob Disease (vCJD) is a special case of an emerging
      infection that is insufficiently well characterized to allow a conclusive
      assessment of its role in the safety of concentrates; however, data regarding the
      capacity of concentrate manufacturing methods to clear the putative agent are
      encouraging. The relative uncertainty surrounding vCJD has caused the influential
      regulatory authorities of North America to take a precautionary approach
      regarding the selection of blood donors. This is having an effect on the supply
      of factor VIII concentrates and has possibly affected the rate at which developed
      countries have switched to recombinant products. The safety of recombinant
      products continues to be supported through patient monitoring, and the new
      generation of plasma protein-free products will further enhance the role of these
      products as the treatment of choice with people with haemophilia. However, their
      cost-effectiveness relative to the current generation of plasma-derived products
      makes it unlikely that they will be accessible by developing countries. The
      dependence of most of the world's population of people with haemophilia on a safe
      and sufficient blood supply will therefore continue into the foreseeable future,
      and with it the need to maintain constant vigilance on blood safety matters.

PMID- 12010418
TI  - Laboratory aspects of haemophilia therapy.

PMID- 12010419
TI  - Modifier genes in haemophilia: their expansion in the human genome.
AB  - Mutations in factor VIII and IX genes have a determinant effect on the severity
      of haemophilia. Modulation of clinical manifestations depends on other genetic
      factors, including modifier genes. In the context of haemophilia, such genes
      could be the ones involved in thrombophilia. Factor V Leiden and prothrombin
      20210A were studied as possible phenotypic modifiers. Inhibitor development after
      therapeutic factor replacement depends on the type of mutation and on the genetic
      factors related to the immune response of each patient. The study of all these
      variants in haemophiliacs constitutes an important step in prevention, prognosis
      and therapeutic alternatives of the disease.

PMID- 12010420
TI  - Development of gene therapy for blood disorders by gene transfer into
      haematopoietic stem cells.
AB  - Haematopoietic stem cells (HSCs) are important target cells for gene therapy of
      blood disorders due to their pluripotency and ability to reconstitute
      haematopoiesis following myeloablation and transplantation. HSCs can 'self-renew'
      and generate new stem cells. Genetically modified stem cells are therefore
      expected to last a lifetime in the recipient following blood and marrow
      transplantation, and can potentially cure haematological disorders.
      Oncoretroviral vectors have been the main vectors used for HSCs because of their
      ability to integrate into the chromosomes of their target cells. Because
      oncoretroviral vectors require dividing target cells for successful localization
      of the preintegration complex and subsequent chromosomal integration of the
      provirus, only the dividing fraction of the target cells can be transduced. As
      only a small fraction of haematopoietic stem cells is dividing at any one time,
      oncoretroviral vector transduction of human HSCs has been low in clinical trials.
      However, patients with severe combined immune deficiency-X1 (SCID-X1) have
      recently been treated successfully by gene therapy of autologous bone marrow
      cells using oncoretroviral vectors containing the common gamma chain gene. While
      several additional disorders may potentially be treated successfully using
      oncoretroviral gene transfer to HSCs, many disorders may require much higher gene
      transfer efficiency than was achieved in the SCID-X1 study. Therefore, lentiviral
      vectors have recently emerged as promising vectors for human HSCs because they
      can transduce dividing and nondividing HSCs efficiently, and may become the
      vectors of choice in the future for treatment of blood disorders where a large
      fraction of HSCs has to be corrected.

PMID- 12010421
TI  - Gene therapy: reality or myth for the global bleeding disorders community?
AB  - In recent years, five different human gene therapy clinical studies have been
      initiated in the United States, covering a broad spectrum of gene transfer
      technologies. Both in vivo and ex vivo studies have been performed, and a variety
      of target organs/tissues have been studied. The results of this early human
      clinical research indicate that there is still much to be done before a safe and
      effective gene therapy procedure becomes commercially available, but there is
      strong evidence that the obstacles that remain will not prove insurmountable.
      Small increases in circulating clotting factor levels have been achieved in some
      patients without significant side-effects, providing proof of the principle that
      gene therapy can provide a therapeutic benefit for patients with haemophilia.
      Still unclear is whether gene therapy, when it becomes available, will be
      accessible to the global haemophilia community. As seen with recombinant and
      other high purity factor concentrates, technological advances do not always lead
      to improvements in care for the majority of the world's haemophilia patients. In
      fact, advances in technology can potentially increase the gulf in care if newer
      processes displace existing manufacturing technologies. A modified vaccine
      production model should be considered to make gene therapy more widely available
      to those who presently have inadequate access to treatment.

PMID- 12010422
TI  - Ethical issues in the genetic aspects of haemophilia.
AB  - The aim of this paper is to put some of the ethical considerations concerning the
      genetic aspects of haemophilia not only in the national, but also in the
      international context, especially from the point of view of human rights.
      Particular attention is given to the issues pertaining to consent from children,
      and the respect for their autonomy within family relationships. This will be
      analysed within the context of genetic screening and testing, as well as codes of
      practice and guidelines. The specific issues around prenatal diagnosis in general
      and pre-implantation genetic diagnosis (PGD) are also discussed.

PMID- 12010423
TI  - Pathophysiology of inhibitors to factor VIII in patients with haemophilia A.
AB  - The occurrence of factor VIII (FVIII) inhibitors is one of the major
      complications of the treatment of haemophilia A. We present this review as a
      description of the major players of the antiFVIII immune response, with
      particular emphasis on the nature and properties of the different antiFVIII
      antibodies, their mechanisms of action in inhibiting FVIII activity, their
      potential neutralization by anti-idiotypic antibodies, and the importance of the
      T cell in participating in the induction of FVIII inhibitors. We briefly conclude
      on the avenues that remain to be explored in order to establish efficient
      therapeutic approaches aimed at eliminating FVIII inhibitors in patients with
      haemophilia A.

PMID- 12010424
TI  - Inhibitors: resolving diagnostic and therapeutic dilemmas.
AB  - The good quality of life now anticipated by individuals with haemophilia A and B
      can be drastically altered by the unpredictable development of an inhibitor, a
      polyclonal high-affinity IgG antibody directed against factor VIII or IX. This
      paper discusses our current state of knowledge about inhibitors within the
      context of: (1) the extent and nature of the problem, including its incidence and
      prevalence, diagnostic options, and the characteristics of the individual
      immunologic response; (2) possible underlying aetiological factors, both
      inherited and situational; and (3) existing and future therapeutic options for
      both the interim treatment of haemorrhage and the ultimate restoration of normal
      clotting factor recovery and survival. Current and future strategies for immune
      tolerisation are also reviewed.

PMID- 12010425
TI  - Orthopaedic surgery in haemophilic patients with inhibitors: an overview.
AB  - Our experience and a review of the literature on inhibitors have shown that, with
      the availability of recombinant factor VIIa (rFVIIa), haemophilic patients with
      high inhibitor titres requiring elective orthopaedic surgery can undergo such
      surgery with a high expectation of success. The advent of rFVIIa has made major
      elective orthopaedic surgery possible in haemophilic patients with high-titre
      inhibitors, resulting in an improved quality of life. Recombinant FVIIa appears
      to be an efficient haemostatic product for surgery in patients suffering from
      haemophilia A and B with inhibitors. The series of major elective orthopaedic
      surgical procedures using rFVIIa (n=53) is the largest ever reported in
      haemophilic patients with inhibitors, despite the long-standing presence of other
      treatment modalities, such as high-dose human factor VIII (FVIII), porcine FVIII
      (n=8), and prothrombin complex concentrates/activated prothrombin complex
      concentrates (n=9). Thorough analysis of each case as part of a multidisciplinary
      team will allow us to perform elective orthopaedic procedures in patients with
      inhibitors.

PMID- 12010426
TI  - von Willebrand disease: still an intriguing disorder in the era of molecular
      medicine.
AB  - von Willebrand disease (vWD) is a single-locus disorder resulting from a
      deficiency of von Willebrand factor (vWF): a multimeric multifunctional protein
      involved in platelet adhesion and platelet-to-platelet cohesion in high shear
      stress vessels, and in protecting from proteolysis and directing circulating
      factor VIII (FVIII) to the site of injury. vWD is the most frequent bleeding
      disorder, with an estimated prevalence in the general population of 1%. Almost
      all these cases are represented by a partial quantitative deficiency of von
      Willebrand factor (vWF) (type 1 vWD). Type 1 is transmitted as an autosomal
      dominant trait with an extremely variable penetrance and expressivity. A
      consensus figure for the prevalence of cases with significant bleeding symptoms,
      requiring some form of treatment, is approximately 100 cases million-1. Among
      these cases, more than 70-80% are represented by type 1 and respond to deamino-D
      arginine vasopressin (DDAVP; desmopressin) administration. The remaining cases
      are represented by type 2 vWD (qualitative), some of which require substitutive
      treatment. Only 3-5 cases million-1 result from a total deficiency of vWF in
      plasma and platelets because of the recessive inheritance of two defective
      alleles. These cases may have severe bleeding episodes and may require frequent
      substitutive treatment. The molecular basis of type 2 (missense mutation in the
      functional domains of the vWF subunit) and type 3 (nonsense or large deletions)
      is quite well understood. On the contrary the molecular basis for most type 1
      cases remains largely unknown, and many genetic factors (e.g. ABO blood group)
      and environmental or circumstantial factors (e.g. age, stress, drugs, pregnancy,
      and inflammation) are superimposed on to the genetic background determined by the
      vWF gene to produce a continuous spectrum from normality to mild type 1 cases. It
      is extremely difficult to make a clear distinction between mild type 1 cases and
      normal people because of the wide 'normal' range of laboratory measurements (e.g.
      length of bleeding time, and levels of vWF and FVIII) and of bleeding symptoms.
      Molecular testing is useless in this situation, and only good history-taking and
      repeated laboratory testing of vWF-related measurements in the propositus and
      his/her family members can help in clinical diagnosis, albeit imprecisely. This
      difficult task is the main focus of this review which is aimed at alerting the
      physician toward a balanced approach that should take into consideration both the
      risk of over- and under-diagnosis of this frequent disorder and the unavoidable
      production of a number of false positive and false negative cases.

PMID- 12010427
TI  - Advances in the therapy of von Willebrand disease.
AB  - von Willebrand disease (vWD) is a very common autosomal inherited bleeding
      disorder, caused by a quantitative deficiency or a qualitative structural defect
      of von Willebrand factor (vWF). Two main therapeutic options are available for
      the treatment of spontaneous bleeding episodes and for prevention of bleeding:
      desmopressin (DDAVP) and replacement therapy with plasma products. DDAVP is the
      treatment of choice for most patients with type 1 vWD. In patients with the type
      3 disease and in most subjects with type 2 disease, DDAVP alone is ineffective or
      contraindicated, and it is usually necessary to switch to plasma concentrates
      containing both factor VIII (FVIII) and vWF. Concentrates subjected to virucidal
      treatment (e.g. solvent/detergent treatment) during manufacture should always be
      used in preference to cryoprecipitate. A recombinant vWF concentrate is now
      undergoing preclinical development and preliminary data suggest it possesses good
      haemostatic function and may correct the bleeding in vWD after its administration
      in several animal models. Although treatment of vWD is relatively simple
      (assuming access to even basic laboratory facilities), actual diagnosis is often
      far from straightforward, and the patients should be well characterized
      phenotypically to tailor the treatment to the different types and subtypes of the
      disease. It is probably wise to refer samples for the characterization to expert
      laboratories.

PMID- 12010428
TI  - Rare coagulation deficiencies.
AB  - Deficiencies of coagulation factors (other than factor VIII and factor IX) that
      cause a bleeding disorder are inherited as autosomal recessive traits and are
      generally rare, with prevalences in the general population varying between 1 :
      500 000 and 1 : 2 000 000. In the last few years, the number of patients with
      recessively transmitted coagulation deficiencies has increased in European
      countries with a high rate of immigration of Islamic populations, because in
      these populations, consanguineous marriages are frequent. Owing to the relative
      rarity of these deficiencies, the type and severity of bleeding symptoms, the
      underlying molecular defects and the actual management of bleeding episodes are
      not as well established as for haemophilia A and B. This article reviews these
      disorders in terms of their clinical manifestations and characterization of the
      molecular defects involved. The general principles of management are also
      discussed. KEYWORDS: afibrinogenaemia, autosomal recessive disorders, factor
      VIII, factor XI, factor XIII.

PMID- 12010429
TI  - The natural history and antiviral treatment of hepatitis C in haemophilia.
AB  - People with haemophilia who received non-virucidally treated large-pool clotting
      factor before 1986 were infected with hepatitis C virus (HCV), previously
      referred to as non-A, non-B hepatitis. Approximately one-tenth of patients have
      been shown to clear infection naturally and shown persistently negative HCV PCR.
      Patients have been infected with genotypes 1, 2 and 3 reflecting the plasma
      donors in Northern Europe and the United States. Several studies have shown that
      HCV mono-infection has a very slow progression. Co-infection with human
      immunodeficiency virus (HIV), however, can hasten the progression to cirrhosis
      and liver failure. Genotype 1 and older age at first infection also increase the
      progression rate. Candidates with detectable HCV RNA are candidates for therapy.
      The combination of standard interferon-alpha and ribavirin doubles the
      effectiveness of interferon-alpha alone and is the current standard of care for
      the treatment of chronic hepatitis C. The duration of therapy depends on the
      genotype and level of viraemia. Patients with genotypes 2 or 3 should have 6
      months' therapy while those with genotype 1 and > 2 million copies mL-1 should
      have 1 year of therapy. Pegylated interferon is an emerging therapy. Patients co
      infected with HIV, in whom treatment has stabilized the HIV infection, may be
      able to tolerate therapy for HCV infection. Liver transplantation is indicated
      for patients with haemophilia who have decompensated hepatitis C infection.

PMID- 12010430
TI  - Menorrhagia from a haematologist's point of view. Part I: initial evaluation.
AB  - The evaluation of menorrhagia should no longer be solely the task of the
      gynaecologist. In women with ovulatory bleeding (regular cycles), the prevalence
      of von Willebrand disease (vWD) in about 15% of these, as well as disorders of
      platelet function and fibrinolysis causing menorrhagia, warrants an active role
      by the haematologist. Initial intake should include documentation of menorrhagia
      by the pictorial chart assessment of menstrual flow. Baseline characteristics of
      menstrual flow should also be documented, including the frequency of changing the
      sanitary pad on the heaviest day, use of more than one sanitary pad at a time,
      number of days lost from school/work and the impact of menses on various quality
      of-life parameters. Menorrhagia since menarche, a past history of surgical-
      and/or dental-related bleeding and a past history of postpartum haemorrhage are
      items of the bleeding symptom audit that appear in part to predict vWD in women
      with menorrhagia. Epistaxis and easy bruising do not appear to be clearly
      discriminatory symptoms. Initial testing should include the complete blood cell
      count, prothrombin time, activated partial thromboplastin time, iron profile,
      serum creatinine, thyroid stimulating hormone level, factor VIII level, vWF
      antigen, ristocetin cofactor and platelet aggregation studies. Additional
      haemostatic studies may also include a factor XI level and euglobulin clot lysis
      time. This extensive medical evaluation should assure both the patient and the
      gynaecologist that the possibility of an underlying haemostatic disorder has been
      thoroughly investigated, to avoid the patient undergoing further costly
      procedures and surgical interventions if an underlying haemostatic disorder
      remains unrecognized.

PMID- 12010431
TI  - Menorrhagia from a haematologist's point of view. Part II: management.
AB  - The management of menorrhagia has until recently been the domain of the
      gynaecologist. As haematologists, we are now addressing the issue of optimal
      management of menorrhagia in our patients with bleeding disorders. Addressing
      three life periods, the menarche, reproductive years, and postchildbearing years,
      this review will discuss the use of oral contraceptive agents, antifibrinolytics,
      non-steroidal anti-inflammatory drugs, intranasal DDAVP and the new
      levonorgestrel-impregnated IUD. Management of specific bleeding disorders will
      also be reviewed for von Willebrand disease, haemophilia A and B carriers, women
      with factor XI deficiency and PAI-1 deficiency.

PMID- 12010432
TI  - Reproductive choices for couples with haemophilia.
AB  - : Summary. The impact of having a child with an inherited bleeding disorder such
      as haemophilia can have a far-reaching effect on the individual as well as other
      close family members. This situation is further complicated in the case of human
      immunodeficiency (HIV) serodiscordant couples, where the haemophilic man is
      affected with HIV through infected blood products whilst his partner is
      seronegative and wanting to have children. It is essential that information on
      the effects of haemophilia, its inheritance, the possibilities of antenatal
      diagnosis, the consideration of selective abortion and the new reproductive
      opportunities available to these couples are made accessible so that an informed
      decision about proceeding with having a family can be made. Couples may wish to
      have a family through nonreproductive methods such as fostering or adoption.
      Alternatively, they may wish to remain childless. In this paper, the terms
      'having children' and 'having a family' will refer to conception through
      biological reproduction. Pre-implantation genetic diagnosis (PGD) offers families
      at risk of having a child with certain inherited genetic disorders the
      opportunity to give birth to an unaffected child. It may be considered as an
      option for couples who would not wish to have prenatal diagnosis leading to
      possible termination of a pregnancy. Assisted conception techniques, such as
      'sperm washing' or the use of 'donor sperm', offer serodiscordant couples
      affected by HIV a risk-reduced or risk-free opportunity, respectively, to have a
      child without infecting the mother, who could in turn infect the fetus by
      vertical transmission. This article, in addition to outlining the inheritance of
      haemophilia and the more common prenatal screening and diagnostic tests,
      discusses in more detail the latest reproductive opportunities available for
      families affected by haemophilia and considering having a family.

PMID- 12010433
TI  - Sexuality and haemophilia: connections across the life-span.
AB  - A broad overview of sexuality issues and needs as they relate to haemophilia are
      presented. Venturing well beyond 'safer sex', sexuality is defined here to
      encompass physical, emotional, social, interpersonal, moral, and cultural
      aspects. From this perspective, sexuality extends beyond behaviour and includes a
      person's thoughts, feelings, nature, and identity. As a means of experiencing
      intimacy, sexuality is a significant factor in achieving quality of life with
      chronic illness. Its impact in haemophilia is influenced by different stages of
      physical and psychosexual development, misconceptions about sexuality, and unique
      concerns for this group, including joint disability, human immunodeficiency
      virus, medication side-effects, and other complications. This paper explores the
      interconnections of sexuality with haemophilia, with a focus on the roles that
      haemophilia care providers can play in addressing these issues. A biopsychosocial
      model of aspects and interrelationships regarding sexuality and haemophilia is
      proposed for use in understanding individuals and planning care approaches. The
      PLISSIT model is offered to guide counselling about sexuality on different levels
      of complexity. Sample strategies for initiating discussion, communicating about
      sex, and developing goals and interventions are presented.

PMID- 12010434
TI  - Orthopaedic surgery of haemophilia in the 21st century: an overview.
AB  - Close co-operation between haematologists, orthopaedic surgeons, rehabilitation
      physicians and physiotherapists is essential for obtaining satisfactory results
      after orthopaedic procedures that are performed on haemophilic patients. Although
      continuous prophylaxis could avoid the development of the orthopaedic
      complications of haemophilia that we still see in the 21st century, such a goal
      has not been achieved so far, not even in developed countries. Therefore,
      orthopaedic surgeons are still required to carry out many different surgical
      procedures, such as arthrocentesis, synoviorthesis, synovectomies, tendon
      lengthening, articular debridements, alignment osteotomies, joint arthroplasties,
      nerve releases, opening of compartment syndromes, removal of pseudotumours and
      osteosynthesis of fractures. Furthermore, the emergence of human immunodeficiency
      virus has meant that immunosuppressed patients in developed countries sometimes
      require an arthrotomy for the treatment of spontaneous septic arthritis, or the
      surgical drainage of a spontaneously infected haematoma (abscess). In addition,
      they have a high risk of postoperative infection after any surgical procedure,
      particularly a joint arthroplasty.

PMID- 12010435
TI  - The treatment of intra-articular synovitis by the use of chemical and radioactive
      substances.
AB  - As the Chairperson of the session relating the intra-articular use of chemical
      and radioactive substances it would seem appropriate to give credit to those who
      contributed to the recent supplement of our Journal Haemophilia. I have extracted
      key sentences and concepts from the contributed articles. All the papers can be
      found in Haemophilia, Volume 7, Supplement 2, July 2001. The title, authors and
      page numbers are provided [1].

PMID- 12010436
TI  - Arthroscopic synovectomy: state of the art.
AB  - Arthroscopic synovectomy for first performed for haemophilic arthropathy in 1980
      and was considered a major improvement over open surgical synovectomy, causing
      less postoperative morbidity and fewer hospitalizations, and preserving range of
      motion. Long-term results have shown that recurrent haemarthroses are decreased
      and joint function is preserved. Radiographic changes, however, suggest continued
      progression of the disease process. The procedure is technically demanding and
      requires considerable resources including skilled personnel, surgical equipment
      and an adequate supply of factor concentrate, all of which limit the availability
      of the procedure worldwide. Where this procedure fits into the treatment of
      chronic haemophilic synovitis depends very much on location and availability of
      resources. Consequently, the procedure should not be considered as the first-line
      approach for recurrent haemarthroses, but rather as a secondary procedure if
      alternative measures have failed.

PMID- 12010437
TI  - Intra-articular hyaluronic acid in the treatment of haemophilic chronic
      arthropathy.
AB  - We report our preliminary experience with the use of hyaluronic acid (Synvisc) in
      29 joints from 25 different haemophilic patients (17 knees, six shoulders, four
      ankles, one elbow and one hip). All the joints were grade III of our
      classification, characterized by synovial thickening, axial deformities and
      muscle atrophy (chronic arthropathy). In view of the very satisfactory results
      obtained with this procedure, we have substituted Synvisc for the previous use of
      intra-articular long-standing corticosteroids that we had been used for some
      years. This method is theoretically more physiological and does not destroy the
      joint cartilage further, as corticosteroids can.

PMID- 12010438
TI  - Total knee replacement in haemophilia.
AB  - We believe that total knee replacement (TKR) is a safe and effective procedure
      for the management of haemophiliac joint arthropathy; however, the increased risk
      of infection and non-infective complications remain a cause for concern. TKR in
      haemophilic patients carries with it an increased risk of post-operative
      infection in comparison to non-haemophiliac patients. Those patients at
      particular risk are the HIV-positive haemophiliac patients whose CD4 count is
      less than 200 cells mm-3. The latest techniques have gone a long way to reducing
      the complication rate and to achieving results that match those of a similar non
      haemophiliac population.

PMID- 12010439
TI  - Total knee arthroplasty in HIV-positive haemophilic patients.
AB  - In the era of total joint replacements in orthopaedics, total knee arthroplasty
      (TKA) should be indicated in haemophilic patients suffering from severe knee pain
      and disability. However, the expected high risk of infection and other
      postoperative complications is a concern. Although the message of this article
      may seem conservative, it should not be inferred that TKA should still be avoided
      in a haemophilic patient, but rather that the orthopaedic surgeon should weigh
      the risks and benefits carefully. Clinical and immunological status should be
      considered before suggesting a total knee replacement to a haemophilic patient.
      If TKA is contraindicated, knee arthrodesis is the alternative. However, knee
      joint debridement can relieve pain for several years and delay the need for TKA.

PMID- 12010440
TI  - Haemophilic cysts (pseudotumours).
AB  - It is very likely that with the advent of widespread maintenance therapy,
      pseudotumours will be less common in the future. It is important that they are
      diagnosed early, and prevention of muscular haematomas is the key to reducing
      their incidence. There are a number of therapeutic alternatives for this
      dangerous condition: surgical removal, percutaneous management, exeresis and
      filling of the dead cavity, irradiation, and embolization. The management of a
      patient with a haemophilic pseudotumour is complex, with a high rate of potential
      complications. Surgical excision is the treatment of choice but should only be
      carried out in major haemophilia centres by a multidisciplinary surgical team.
      The main postoperative complications are death, infection, fistulization, and
      pathological fractures (even requiring amputations of affected limbs). Pelvic
      pseudotumours can even become complicated by fistulization to the large bowel and
      by obstruction of the ureters. Untreated, proximal pseudotumours will ultimately
      destroy soft tissues, erode bone, and may produce neurovascular complications.

PMID- 12010441
TI  - Haemophilic pseudotumours of the limbs and their percutaneous treatment.
AB  - The percutaneous treatment of limb pseudotumours is a nonaggressive method of
      treating haemophilic pseudotumours. However, efforts should be directed to the
      prevention of such pseudotumours by ensuring that all patients receive adequate
      treatment of their bleeding episodes through education and the elimination of
      geographical or social barriers that prevent access to such treatment. Prevention
      of pseudotumours by means of early substitution treatment of muscular bleeding
      episodes is the best treatment.

PMID- 12010442
TI  - Orthoses in haemophilia.
AB  - In haemophilia patients, orthoses are used for the prevention and management of
      bleeds and their effects on the musculoskeletal system. The characteristics of
      these devices vary according to the joint to which they are applied, although two
      basic types are distinguished: static and functional. The upper limbs make up a
      functional unit that is adapted to prehension, or the action of grasping or
      seizing objects. The most affected joints of this unit in haemophilia are the
      elbow and shoulder, which require immobilization, followed by stabilization and
      protection and in the case of disability, assistance in the performance of
      function. The lower limbs, on the other hand, are adapted to the action of
      ambulation. The knee, ankle and hip joints frequently sustain damage in
      haemophilia, and in the acute phase they should be immobilized and the patient
      discouraged from walking. Once bleeding has ceased, and motion and muscle balance
      improved, a gradual return to normal activity may commence. The principle aim of
      orthotics in these cases is to immobilize and unburden the affected body segment,
      and to provide stability and assistance for ambulation. Shoe insoles cushion and
      modify stance, and therefore may help prevent lesions. Crutches and walking
      frames are used for restoring normal gait. Orthotic devices improve the quality
      of life of haemophilia patients with musculoskeletal lesions and are useful for
      preventing lesions resulting from strenuous activities, whether performed in the
      course of daily living or in the pursuit of games and sports.

PMID- 12010443
TI  - Current concepts in electrotherapy.
AB  - Electrotherapy has an established role in the management of a wide range of
      musculoskeletal and neurological problems. Used in conjunction with other
      therapeutic interventions, it can make a positive contribution to patient care.
      The means by which a range of different exogenous energy forms can influence the
      physiological state of the tissue is well documented. Different therapeutic
      modalities achieve their effects in different tissues, and the clinical decision
      making process should employ the available evidence in order to maximize the
      potential benefit for each patient. The applied energy essentially acts as a
      trigger that is responsible for stimulating, enhancing or activating particular
      physiological events, which in turn are utilized to achieve therapeutic benefit.
      There appear to be windows of opportunity related to the magnitude of the applied
      energy, the amplitude of the stimulus and the frequency of application. Tissues
      appear to vary in their responsiveness to these factors, and thus an appropriate
      modality applied in an inappropriate manner will fail to achieve the anticipated
      effect. This paper aims to review the current concepts of electrotherapy
      intervention, taking into account various theories which support the principles.
      Application of various energies in this way can result in significant benefit for
      the patient.

PMID- 12010444
TI  - Clinimetric instruments to assess functional health status in patients with
      haemophilia: a literature review.
AB  - The World Federation of Hemophilia scoring system (WFH-1) evaluates primarily
      body functions and structures, whereas assessment of the whole area of functional
      health status is considered nowadays to be a better measure. In addition, the WFH
      1 lacks psychometric properties (reliability, validity and sensitivity to
      change). This study aimed to gain insight into the clinimetric assessment of
      functional health status in patients with haemophilia by way of a systematic
      literature search. A standardized literature search and selection was performed
      on the databases of CINAHL (1982-2001), Medline (1966-2001), and PubMed (January
      July 2001). Clinimetric instruments applied in the selected articles were
      classified based on the international classification of functioning, disability,
      and health (ICF) and analysed for their psychometric properties. In 19 articles
      published between 1979 and 2001, 34 clinimetric instruments were used to assess
      functional health status. Instruments were classified as measuring the ICF
      components body structure and function (n = 17), activities (12) and
      participation (4). Reliability was measured in four articles on three different
      instruments, the validity (construct) of the instruments for patients with
      haemophilia was reported in six articles on five instruments, and sensitivity to
      change in three articles on three instruments. The populations under study varied
      in number (7-9 35), mean age (21.6-50.8 years), and in the distribution of
      haemophilia severity. Reports on the evaluation of functional health status in
      patients with haemophilia are increasing. Further research on the psychometric
      properties of the instruments is warranted in more groups of patients with
      haemophilia. Development of the new core set of clinimetric instruments, the WFH
      2, might benefit from this strategy.

PMID- 12010445
TI  - Evaluation of outcome of care in patients with haemophilia.
AB  - Haemophilia is a potentially disabling condition associated with high financial
      costs, and so the need for robust measures to evaluate outcome of care is
      essential. This paper is a review of some of the outcome measures commonly used
      to evaluate treatment in haemophilia and includes quality of life measures,
      evaluation of the musculoskeletal system and orthopaedic surgical procedures.
      Quality-of-life questionnaires are discussed with particular reference to the
      SF36 and AIMS2. Results of published studies to date have demonstrated variable
      results. Overall, haemophilia appears to reduce quality of life compared to
      normal population figures. Several factors are perceived to reduce quality of
      life, and these include being human immunodeficiency virus (HIV) positive, having
      impairments, and a history of orthopaedic surgery. The evaluation of the
      musculoskeletal system is important in order to detect any deterioration over
      time. Various standardized measurement tools are described. Orthopaedic surgical
      procedures have also been evaluated in patients with haemophilia. To date, the
      Hospital for Special Surgery Knee rating scale has been the most commonly used to
      evaluate the outcome of total knee replacement. The limitations of this system
      for patients with haemophilia are outlined. Overall, these measures provide
      useful tools for evaluating outcome, but none have been specifically developed
      for patients with haemophilia. Further studies would be useful to evaluate these
      tools and others in more depth.

PMID- 12010446
TI  - Progress in haemophilic care: ethical issues.
AB  - Care of haemophilic patients has dramatically improved during the past 40-50
      years. Clotting factor concentrates have become much safer. Expensive treatments
      such as prophylaxis, immune-tolerance induction, the use of bypassing agents in
      inhibitor patients, and the replacement of joints have become available. However,
      there is still a shortage of factor concentrate, and we are yet to discover the
      most cost-effective treatment for patients. There is also a wide gap in the
      availability of these treatments between developing and developed countries, and
      a risk that patients are treated in unnecessarily expensive ways in some parts of
      the world compared with those who suffer from a lack of treatment in other parts,
      thus creating the ethical dilemma of whether less safe but more affordable
      concentrates should be used in developing countries. Other issues that raise
      ethical problems are the use of molecular genetics and gene therapy. It is
      proposed that international working groups, preferably under the auspices of the
      World Health Organisation and the World Federation of Hemophilia, take
      responsibility to solve the ethical issues in haemophilic care, the basis of
      which should be to promote the education of modern care and to set up clinical
      studies, including studies on health economics, so that treatment and care are
      cost-effective and based on sound evidence.

PMID- 12010447
TI  - Ethics of haemophilia care in the developing world.

PMID- 12010448
TI  - Patient autonomy: evolution of the doctor-patient relationship.
AB  - In recent years, much has been said about the shifting locus of control in
      clinical practice. This article discusses the influence on the physician-patient
      relationship of recent social and political history, patient culture and
      experience, and advances in medical practice. I suggest that effective
      partnerships between physicians and patients are possible in a supportive
      institutional environment in which the participants acknowledge and fulfil their
      roles and responsibilities in shared decision-making. While I recognize that
      there is considerable variability in practices across cultures and in individual
      behaviour, the scope of this article is based on literature and my knowledge,
      which is representative primarily of the North American experience.

PMID- 12010449
TI  - Becoming a partner in your healthcare.
AB  - Chronic disorders such as haemophilia and von Willebrand disease can rob people
      of a feeling of control over their lives. Added to this is often a feeling of
      confusion or intimidation when dealing with the healthcare system. People may
      begin to feel like victims of their disorders and of the healthcare system. The
      healthcare system defines people who are in receipt of care as patients. The word
      patient comes from the Latin word patiens, which means to suffer, endure, allow,
      permit or undergo. Even the term implies a sense of victimization. People who
      become partners in their care and view the receipt and delivery of healthcare as
      a service wherein they are the consumer and the doctor or clinician is the
      provider, will feel more in control and will likely have better outcomes than
      people who assume the more traditional role of 'patient'.

PMID- 12010450
TI  - The physician-patient relationship: recent developments and changes.

PMID- 12010451
TI  - Access to medical information in Spain.
AB  - The 21st century is marked by advances in medical science and the rise of the
      'information society'. It is possible to identify and systematize the
      intersections between both of these areas and point out a matrix of access to
      medical information from a legal perspective. There are four connecting levels:
      (1) informed consent; (2) medical histories; (3) healthcare administrative
      information; and (4) information on the impact of environmental factors such as
      food and nutrition or contamination on health. This four-way scenario acquires
      new importance with the generalization of the information society and the
      advances in biomedicine. Globalization is challenged by the 'here and now'
      mentioned before. The large number of medical data and their new uses and
      consequences is a subject requiring an interdisciplinary approach that emerges
      from ethics as much as from science.

PMID- 12010452
TI  - The impact of chronic disease on the family.
AB  - Haemophilia is a chronic disease, affecting patients and their families. The
      impact of such a disease upon each family is dependent upon family type and
      characteristics and adjustment to it varies with time, in concordance with the
      family's lifecycle. In the National Hemophilia Center in Israel we lead a special
      support system and conduct group therapy from the very early stage of haemophilia
      diagnosis throughout the lifetime of patients. The general definitions of a
      family's lifecycle, the effect of the disease and the required adjustment to it
      are described in this paper. We refer to special difficulties associated with
      haemophilia as a chronic, genetic disease and describe ways to cope, discussing
      the support systems that have been established in our centre.

PMID- 12010453
TI  - Education and career development.
AB  - The main objective of this paper is to briefly analyse the different factors and
      circumstances that a person with haemophilia should take into account before
      undertaking the challenge of going to university and, in turn, choosing a
      profession or career. Although education systems in different countries or
      regions present fundamental differences, some characteristics remain the same,
      and these will be the focus of our study. The child with haemophilia will most
      likely encounter three challenges: (1) the challenge of choosing a career; (2)
      the challenge of choosing a college or university; and (3) the challenge of
      adjusting to college or university life. The young haemophiliac should be taught
      to exploit their strengths, and to feel that their only limit is their
      intellectual development. They should feel that they are only competing against
      themselves and that any adversities they might face due to haemophilia should not
      disfavour them; instead they should learn how to live with them and allow these
      to make them into stronger people.

PMID- 12010456
TI  - Ubiquitin-related modifier SUMO1 and nucleocytoplasmic transport.
AB  - Small ubiquitin related modifier SUMO-1 and its homologs can be conjugated to a
      large number of cellular proteins. This involves an enzymatic cascade that
      resembles ubiquitination, and the modification can be reverted by isopeptidases.
      SUMOylation does not lead to degradation but instead appears to regulate
      protein/protein interactions, intracellular localization and protects some
      modified targets from ubiquitin-dependent degradation. Data collected for more
      than 30 different target proteins point to two cellular processes,
      nucleocytoplasmic transport and intranuclear targeting, in which SUMO plays an
      active role. Here we will focus on links between SUMO and nuclear transport.

PMID- 12010457
TI  - Hassles with taking out the garbage: aggravating aggresomes.
AB  - Diverse human diseases ranging from amyloidosis to neurodegenerative diseases are
      now recognized as 'conformational diseases' caused by protein misfolding and
      protein aggregation. Misfolded and aggregated proteins are usually handled in the
      cell through chaperone-mediated refolding, or when that is impossible, destroyed
      by proteasomal degradation. Recent evidence suggests that cells might have
      evolved a third pathway that involves the sequestration of aggregated proteins
      into specialized 'holding stations' called aggresomes. The aggresomal pathway
      provides a mechanism by which aggregated proteins form particulate (approximately
      200 nm) mini-aggregates that are transported on microtubules (MTs) towards the MT
      organizing center (MTOC) by a process mediated by the minus-end motor protein
      dynein. Once at the MTOC, the individual particles pack into a single, usually
      spherical aggresome (1-3 microm) that surrounds the MTOC. Aggresomes are dynamic:
      they recruit various chaperones and proteasomes, presumably to aid in the
      disposal of the aggregated proteins. In addition, the formation of an aggresome
      is likely to activate the autophagic clearance mechanism that terminates in
      lysosomal degradation. Hence, the aggresome pathway may provide a novel system to
      deliver aggregated proteins from the cytoplasm to lysosomes for degradation.
      Although it is clear that many pathological states correlate with the formation
      of aggresomes, their causal relationships remain hotly debated. Here, we describe
      the current state of our knowledge of the aggresome pathway and outline the open
      questions that provide the focus of current research.

PMID- 12010458
TI  - Low pH inhibits compensatory endocytosis at a step between depolarization and
      calcium influx.
AB  - Cell function can be modulated by the insertion and removal of ion channels from
      the cell surface. The mechanism used to keep channels quiescent prior to delivery
      to the cell surface is not known. In eggs, cortical vesicle exocytosis inserts
      voltage-gated calcium channels into the cell surface. Calcium influx through
      these channels triggers compensatory endocytosis. Secretory vesicles contain high
      concentrations of calcium and hydrogen ions. We propose that lumenal hydrogen
      ions inhibit vesicular calcium channel gating prior to exocytosis, discharge of
      lumenal protons upon vesicle-plasma membrane fusion enables calcium channel
      gating. Consistent with this hypothesis we find that cortical vesicle lumens are
      acidic, and exocytosis releases lumenal hydrogen ions. Acidic extracellular pH
      reversibly blocks endocytosis, and the windows of opportunity for inhibition with
      a calcium-channel blocker or hydrogen ions are indistinguishable. Calcium
      ionophore treatment circumvents the low pH block, suggesting that calcium influx,
      or an upstream step, is obstructed. Inhibition of calcium influx by preventing
      membrane depolarization is unlikely, as elevation of the extracellular potassium
      concentration failed to overcome the pH block, and low extracellular pH was found
      to depolarize the membrane potential. We conclude that low pH inhibits
      endocytosis at a step between membrane depolarization and calcium influx.

PMID- 12010459
TI  - SifA, a type III secreted effector of Salmonella typhimurium, directs Salmonella
      induced filament (Sif) formation along microtubules.
AB  - A unique feature of Salmonella enterica serovar typhimurium (S. typhimurium) is
      its ability to enter into (invade) epithelial cells and elongate the vacuole it
      occupies into tubular structures called Salmonella-induced filaments (Sifs). This
      phenotype is dependent on SifA, a Salmonella virulence factor that requires the
      SPI-2-encoded type III secretion system for delivery into host cells. Previous
      attempts to study SifA and other type III secreted proteins have been limited by
      a lack of suitable reagents. We examined SifA function by expressing SifA with
      two internal hemagglutinin epitope tags. By employing subcellular fractionation
      techniques, we determined that translocated SifA was membrane associated in
      infected HeLa cells. Confocal microscopy revealed that SifA associated with the
      Salmonella vacuole and with Sifs. Our analysis also revealed that microtubules
      serve as a scaffold for Sifs, and that SifA colocalizes with microtubules at
      sites of interaction between lysosomal glycoprotein-containing vesicles and Sifs.
      Treatment with the microtubule inhibitor nocodazole blocked Sif formation but did
      not prevent SifA translocation into the Salmonella vacuole. While polymerized
      actin has been observed on Sifs, this phenotype was transient and did not play a
      role in promoting or maintaining Sif formation. Our findings demonstrate the
      essential role of microtubule dynamics in the formation of Sifs and the utility
      of this epitope tagging strategy for the study of bacterial type III secreted
      proteins.

PMID- 12010460
TI  - Role of Rab5 in the recruitment of hVps34/p150 to the early endosome.
AB  - PI 3-kinases are important regulators of endocytic trafficking. We have
      previously proposed a model in which the Rab5 GTPase recruits EEA1 to the early
      endosome both directly, by binding to EEA1, and indirectly, through the
      recruitment of the p150/hVps34 PI 3-kinase and the production of PI[3]P in the
      endosomal membrane. In this study we have examined this model in vivo. We find
      that both endogenous hVps34 and p150 are targeted to enlarged endosomal
      structures in cells expressing constitutively activated Rab5, where they are
      significantly colocalized with EEA1. Recombinant fragments of p150 disrupt the
      endosomal localization of EEA1, showing that p150 is required for EEA1 targeting.
      We further analyzed the mechanism of GTP-dependent Rab5-p150 binding, and showed
      the p150 HEAT and WD40 domains are required for binding, whereas deletion of the
      protein kinase domain increases binding to Rab5. Overexpression of constitutively
      active Rab5 caused a redistribution of epitope-tagged hVps34 and p150 to Rab5
      positive endosomes. However, subcellular fractionation showed that this was not
      due to a significant recruitment of hVps34 or p150 from the cytosolic to the
      particulate fraction. These data suggest that the binding of Rab5 to the
      HEAT/WD40 domains of p150 is important in regulating the localization of
      hVps34/p150. However, Rab5 does not appear to act by directly recruiting
      p150/hVps34 complexes from the cytosol to the endosomal membrane.

PMID- 12010461
TI  - CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles.
AB  - Several peripheral membrane proteins associated with clathrin-coated vesicles
      (CCVs) are reversibly phosphorylated, but it is not clear precisely which protein
      kinases are involved. In order to address this question directly, we have
      isolated highly purified CCVs from porcine brain. The peripheral membrane
      proteins have been removed and assayed for kinase activity using the CCV
      peripheral membrane proteins as substrate. The major kinase activity identified
      has a molecular mass of 40 kDa, is inhibited by known specific inhibitors of the
      protein kinase CK2 and is recognised by an antibody specific to CK2. We show that
      CK2 is responsible for the phosphorylation of the majority of CCV-associated
      proteins that are subject to phosphorylation. Intriguingly, CK2 is inactive when
      associated with CCVs but becomes active once the clathrin coat has been removed.
      The medium subunit of the AP2 adaptor complex (mu2) is not a substrate for CK2,
      but is phosphorylated by a second kinase that we show to be cyclin G-associated
      kinase (GAK/auxilin2). Unlike the situation for the CK2 substrates, mu2 is a
      substrate for GAK/auxilin2, both in intact CCVs and in solution. In addition, we
      show that the 'stripped' CCV membranes that remain once the peripheral membrane
      proteins have been removed from CCVs inhibit CK2 but not GAK/auxilin2 activity.

PMID- 12010462
TI  - Phosphate sensing in higher plants.
AB  - Phosphate (Pi) plays a central role as reactant and effector molecule in plant
      cell metabolism. However, Pi is the least accessible macronutrient in many
      ecosystems and its low availability often limits plant growth. Plants have
      evolved an array of molecular and morphological adaptations to cope with Pi
      limitation, which include dramatic changes in gene expression and root
      development to facilitate Pi acquisition and recycling. Although physiological
      responses to Pi starvation have been increasingly studied and understood, the
      initial molecular events that monitor and transmit information on external and
      internal Pi status remain to be elucidated in plants. This review summarizes
      molecular and developmental Pi starvation responses of higher plants and the
      evidence for coordinated regulation of gene expression, followed by a discussion
      of the potential involvement of plant hormones in Pi sensing and of molecular
      genetic approaches to elucidate plant signalling of low Pi availability.
      Complementary genetic strategies in Arabidopsis thaliana have been developed that
      are expected to identify components of plant signal transduction pathways
      involved in Pi sensing. Innovative screening methods utilize reporter gene
      constructs, conditional growth on organophosphates and the inhibitory properties
      of the Pi analogue phosphite, which hold the promise for significant advances in
      our understanding of the complex mechanisms by which plants regulate Pi
      starvation responses.

PMID- 12010463
TI  - Regulation of the tetrapyrrole biosynthetic pathway leading to heme and
      chlorophyll in plants and cyanobacteria.
AB  - Photosynthetic organisms synthesize chlorophylls, hemes, and bilin pigments via a
      common tetrapyrrole biosynthetic pathway. This review summarizes current
      knowledge about the regulation of this pathway in plants, algae, and
      cyanobacteria. Particular emphasis is placed on the regulation of glutamate-1
      semialdehyde formation and on the channelling of protoporphyrin IX into the heme
      and chlorophyll branches. The potential role of chlorophyll molecules that are
      not bound to photosynthetic pigment-protein complexes ('free chlorophylls') or of
      other Mg-containing porphyrins in regulation of tetrapyrrole synthesis is also
      discussed.

PMID- 12010464
TI  - The third myrosinase gene TGG3 in Arabidopsis thaliana is a pseudogene
      specifically expressed in stamen and petal.
AB  - Genomic clones and full-length cDNA for the myrosinase gene TGG3 from Arabidopsis
      thaliana ecotype Columbia were sequenced. The TGG3 gene was similar with the
      earlier described myrosinase genes and shared the conserved intron/exon splice
      sites but had an insertion of one nucleotide in exon 5, a deletion of two
      nucleotides in exon 6 and a deletion of approximately 210 nucleotides in exon 12.
      These mutations shifted the open reading frame in exon 5 and resulted in a
      truncated protein. Analysis of the TGG3 DNA sequence from five other Arabidopsis
      ecotypes showed polymorphisms, but in no case did a functional TGG3 gene appear
      to be present. Although TGG3 apparently is a pseudogene, it was expressed
      specifically in stamen and petal according to RT-PCR analysis, while TGG1 and
      TGG2 transcripts were present in most of the tested tissues. Western blot
      analysis showed only one myrosinase band of 68 kDa corresponding to TGG1 and TGG2
      in flower samples, while no band corresponding to TGG3 was encountered.
      Apparently only two functional myrosinases are present in this gene family in
      Arabidopsis.

PMID- 12010465
TI  - Sucrose uptake, invertase localization and gene expression in developing fruit of
      Lycopersicon esculentum and the sucrose-accumulating Lycopersicon hirsutum.
AB  - By using immunolocalization and differential extraction methods we show that only
      apoplastic invertase, but not vacuolar invertase, was present in the mature,
      sucrose-accumulating L. hirsutum pericarp. In contrast, in the hexose
      accumulating L. esculentum fruit, both the apoplastic and vacuolar invertase
      activities and protein content increase in the mature fruit. Quantitative
      expression studies of the soluble invertase gene (TIV1) and the apoplastic
      invertase genes (LINs) showed that only TIV1 gene expression could account for
      the species and developmental differences of both soluble and insoluble enzyme
      activity of the pericarp. The expression of the LIN genes encoding for apoplastic
      tomato invertases was unrelated to the differences in bound enzyme activity and
      could not account for the rise in bound invertase activity in the mature L.
      esculentum fruit. Evidence is presented that the bound invertase activity of
      tomato fruit is also the TIV1 gene product. The presence of apoplastic invertase
      in the mature sucrose-accumulating L. hirsutum fruit suggests a hydrolysis
      resynthesis mechanism of sucrose uptake. In order to test this hypothesis, we
      studied short- and long-term uptakes of asymmetrically labelled 3H-fructosyl
      sucrose accompanied by compartmental analysis of the sugars in attached whole
      fruits of L. hirsutum and L. esculentum. The results indicate that hydrolysis
      resynthesis is slow in the sucrose-accumulating fruit but is not an integral part
      of an uptake and compartmentation mechanism.

PMID- 12010466
TI  - Isolation of mannose 6-phosphate reductase cDNA, changes in enzyme activity and
      mannitol content in broomrape (Orobanche ramosa) parasitic on tomato roots.
AB  - We are interested in developing a control strategy efficient at the early stages
      of subterranean development of Orobanche in the inhibition of mannose 6-phosphate
      reductase (M6PR, EC 1.1.1.224), the key enzyme of mannitol production in the
      parasite. We examined M6PR gene expression during pre-conditioning, germination,
      procaulome growth, underground shoot development and emergence of Orobanche
      ramosa L. attached to tomato roots, the enzyme activity at each of the above
      stages and the level of stored mannitol in the parasite. A 1120-pb length cDNA
      isolated by 3' and 5'RACE was identified as a M6PR sequence by cDNA expression in
      E. coli and M6PR activity measurement. Only one M6PR gene was detected in O.
      ramosa following southern blot analysis. M6PR expression, analysed by RT-PCR, was
      constant from the pre-conditioned seed to the emergence of broomrape, i.e. M6PR
      expression is constitutive in Orobanche. M6PR activity was also detected in pre
      conditioned seeds and attachment to tomato roots resulted in a two-fold increase
      in enzyme activity during tubercle enlargement and crown root formation. Hexose
      and mannitol accumulation was strongly enhanced in the attached parasite, with
      accumulation primarily in the shoot. These results support the prospect of
      utilizing M6PR inhibitors as early applied herbicides to control this parasite in
      the early stages of its development.

PMID- 12010467
TI  - Adenine phosphoribosyltransferase isoforms of Arabidopsis and their potential
      contributions to adenine and cytokinin metabolism.
AB  - Adenine phosphoribosyltransferase (APT; EC 2.4.2.7) is a constitutively expressed
      enzyme involved in the one-step salvage of adenine to AMP. The Arabidopsis
      thaliana genome contains five sequences annotated as encoding APT or APT-like
      enzymes. Three of these have now been cloned, over-expressed and compared using
      kinetic analyses. At a cytosolic pH, all bind adenine efficiently based on their
      Km values (0.8-2.6 &mgr;M), although APT1 metabolizes adenine at a rate 31-53
      times faster than APT2 and APT3, respectively. Since APT also has a possible role
      in the interconversion of cytokinin bases to nucleotides, we characterized the
      activity of each isoform on zeatin, isopentenyladenine and benzyladenine. Based
      on their Km values, APT2 and APT3 had much higher affinities than APT1 for all
      three cytokinins (15-440 &mgr;M for APT2 and 3 vs. 1.8-2.5 mM for APT1);
      conversely the Vmax values for APT2 and APT3 on these CK substrates showed the
      opposite trend, being 4- to 19-fold lower than those of APT1. Anti-peptide
      antibodies for APT1, APT2, and APT3 were prepared and used to examine the
      subcellular localization of each isoform. Based on these results, APT1 and APT3
      appear to be cytosolic, while the localization of APT2 was inconclusive although
      sequence analysis implies that APT2 is also cytosolic. Each isoform was modelled
      against the crystal structure of APT from Leishmania donovani, and structural
      differences in substrate specificity-determining domains have been found. The
      estimated kinetic activities of these APTs suggest that they contribute primarily
      to adenine recycling, although an involvement in cytokinin interconversion cannot
      be discounted.

PMID- 12010468
TI  - Cloning and functional characterization of a homoglutathione synthetase from pea
      nodules.
AB  - The thiol tripeptide glutathione (GSH; gammaGlu-Cys-Gly) is very abundant in
      legume nodules where it performs multiple functions that are critical for optimal
      nitrogen fixation. Some legume nodules contain another tripeptide,
      homoglutathione (hGSH; gammaGlu-Cys-betaAla), in addition to or instead of GSH.
      We have isolated from a pea (Pisum sativum L.) nodule library a cDNA, GSHS2, that
      is expressed in nodules but not in leaves. This cDNA was overexpressed in insect
      cells and its protein product was identified as a highly active and specific hGSH
      synthetase. The enzyme, the first of this type to be completely purified, is
      predicted to be a homodimeric cytosolic protein. It shows a specific activity of
      3400 nmol hGSH min-1 mg-1 protein with a standard substrate concentration (5 mM
      beta-alanine) and Km values of 1.9 mM for beta-alanine and 104 mM for glycine.
      The specificity constant (Vmax/Km) shows that the pure enzyme is 57.3-fold more
      specific for beta-alanine than for glycine. Southern blot analysis revealed that
      the gene is present as a single copy in the pea genome and that there are
      homologous genes in other legumes. We conclude that the synthesis of hGSH in pea
      nodules is catalysed by a specific hGSH synthetase and not by a GSH synthetase
      with broad substrate specificity.

PMID- 12010469
TI  - Winter-drought induced embolism in Norway spruce (Picea abies) at the Alpine
      timberline.
AB  - At the timberline in the Central Alps, climatic conditions during winter
      frequently cause excessive drought stress (frost drought, 'Frosttrocknis'), which
      we hypothesized to induce cavitation in trees. We investigated the extent of
      winter-embolism in Norway spruce (Picea abies (L.) Karst.) growing near the
      timberline and analysed adaptations in vulnerability and anatomy. We found
      conductivity losses of up to 100% at the highest elevation (2020 m) correlated
      with low water potentials down to - 4.0 MPa. Vulnerability thresholds (50% loss
      in conductivity) decreased from - 3.39 MPa at 800 m to - 3.88 MPa at 1600 m
      corresponding to a decrease in tracheid cross-sectional area as well as pit and
      pit pore diameters. These thresholds were lower than potentials measured in
      embolized twigs near the timberline at the sampling dates probably due to lower
      potentials and/or a role of freeze-thaw events earlier in winter. Data indicated
      refilling processes, which may be of particular relevance for trees at the
      timberline, since adaptations in drought-induced vulnerability failed to prevent
      winter-embolism.

PMID- 12010470
TI  - A new biochemical marker for aluminium tolerance in plants.
AB  - Al was shown to elicit the induction of several pathogenesis-related genes,
      suggesting that a common signalling pathway may be involved in the early response
      to Al and pathogens. However, we found no evidence of oxidative burst involving
      either H2O2 or O2- during the first hours of Al exposure distinguishing the early
      response to Al from a common response to pathogen infection. We identified a
      strong superoxide dismutase insensitive nitro blue tetrazolium (NBT) reduction
      activity in the root tips of control plants. This activity was rapidly inhibited
      by Al exposure in the meristematic/distal transition zones of roots in all
      species examined. In wheat (Triticum aestivum), the inhibition of NBT reduction
      occurred in less than 1 min in vivo suggesting that Al either directly blocks an
      enzyme responsible for NBT reduction, or affects a signal pathway involved in the
      regulation of this activity. The sensitivity of NBT reduction to KCN and NaN3
      suggests that an enzymatic, rather than a chemical reaction is involved. In
      tolerant plants, the inhibition of NBT reduction caused by Al was reversed within
      24 h of exposure. The level of recovery was a function of the degree of Al
      tolerance. We show that NBT reduction is a simple biochemical marker allowing the
      rapid identification of tolerant individuals within a segregating population.

PMID- 12010471
TI  - Silicification in sorghum (Sorghum bicolor) cultivars with different drought
      tolerance.
AB  - Sorghum belongs to a group of economically important, silicon accumulating
      plants. X-ray microanalysis coupled with environmental scanning electron
      microscopy (ESEM) of fresh root endodermal and leaf epidermal samples confirms
      histological and cultivar specificity of silicification. In sorghum roots,
      silicon is accumulated mostly in endodermal cells. Specialized silica aggregates
      are formed predominantly in a single row in the form of wall outgrowths on the
      inner tangential endodermal walls. The density of silica aggregates per square mm
      of inner tangential endodermal cell wall is around 2700 and there is no
      significant difference in the cultivars with different content of silicon in
      roots. In the leaf epidermis, silicon deposits were present in the outer walls of
      all cells, with the highest concentration in specialized idioblasts termed
      'silica cells'. These cells are dumb-bell shaped in sorghum. In both the root
      endodermis and leaf epidermis, silicification was higher in a drought tolerant
      cultivar Gadambalia compared with drought sensitive cultivar Tabat. Silicon
      content per dry mass was higher in leaves than in roots in both cultivars. The
      values for cv. Gadambalia in roots and leaves are 3.5 and 4.1% Si, respectively,
      and for cv. Tabat 2.2 and 3.3%. However, based on X-ray microanalysis the amount
      of Si deposited in endodermal cell walls in drought tolerant cultivar (unlike the
      drought susceptible cultivar) is higher than that deposited in the leaf
      epidermis. The high root endodermal silicification might be related to a higher
      drought resistance.

PMID- 12010472
TI  - Water relations and gas exchange in poplar and willow under water stress and
      elevated atmospheric CO2.
AB  - Predictions of shifts in rainfall patterns as atmospheric [CO2] increases could
      impact the growth of fast growing trees such as Populus spp. and Salix spp. and
      the interaction between elevated CO2 and water stress in these species is
      unknown. The objectives of this study were to characterize the responses to
      elevated CO2 and water stress in these two species, and to determine if elevated
      CO2 mitigated drought stress effects. Gas exchange, water potential components,
      whole plant transpiration and growth response to soil drying and recovery were
      assessed in hybrid poplar (clone 53-246) and willow (Salix sagitta) rooted
      cuttings growing in either ambient (350 &mgr;mol mol-1) or elevated (700 &mgr;mol
      mol-1) atmospheric CO2 concentration ([CO2]). Predawn water potential decreased
      with increasing water stress while midday water potentials remained unchanged
      (isohydric response). Turgor potentials at both predawn and midday increased in
      elevated [CO2], indicative of osmotic adjustment. Gas exchange was reduced by
      water stress while elevated [CO2] increased photosynthetic rates, reduced leaf
      conductance and nearly doubled instantaneous transpiration efficiency in both
      species. Dark respiration decreased in elevated [CO2] and water stress reduced Rd
      in the trees growing in ambient [CO2]. Willow had 56% lower whole plant hydraulic
      conductivity than poplar, and showed a 14% increase in elevated [CO2] while
      poplar was unresponsive. The physiological responses exhibited by poplar and
      willow to elevated [CO2] and water stress, singly, suggest that these species
      respond like other tree species. The interaction of [CO2] and water stress
      suggests that elevated [CO2] did mitigate the effects of water stress in willow,
      but not in poplar.

PMID- 12010473
TI  - Abscisic acid- and cold-induced thaumatin-like protein in winter wheat has an
      antifungal activity against snow mould, Microdochium nivale.
AB  - Cold acclimation of winter wheat (Triticum aestivum L.) seedlings induces
      accumulation in the apoplast of taTLPs that are similar to thaumatin-like
      proteins (TLPs), which are pathogenesis-related proteins. We characterized a cDNA
      of WAS-3a encoding the major isoform of taTLPs from winter wheat cells and showed
      that WAS-3a transcripts were markedly increased by treatment with ABA and by
      treatment with elicitors (chitosan, beta-glucan and cell wall fractions of
      Fusarium oxysporum and Microdochium nivale) in wheat cells. To analyse the
      function of WAS-3a, a highly efficient expression system using wheat cells was
      established, and a large amount of recombinant WAS-3a protein (rWAS-3a) was
      obtained with near homogeneity. Antifungal assays using various fungi grown on
      agar plates revealed that rWAS-3a inhibits hyphal growth of pink snow mould,
      Microdochium nivale, at a low temperature. The results suggest that cold-induced
      taTLPs that accumulate in the apoplast contribute to snow mould resistance of
      winter wheat.

PMID- 12010474
TI  - Root zone calcium modulates the response of potato plants to heat stress.
AB  - Potato plant growth and development are known to be severely impacted by heat
      stress. Here plants grown in a chemically inert medium of 1 : 1 quartzite :
      perlite (v : v) were subjected to either 35/25 degrees C (stress) or 20/15
      degrees C (control) day/night air temperatures and four concentrations of root
      zone calcium (5, 25, 125 and 600 &mgr;M Ca) for 3 weeks. We report for the first
      time that potato plant growth under heat stress can persist at specific levels of
      Ca2+ in the root zone and that the Ca2+ level required for growth under heat
      stress exceeds that required for growth under normal temperatures. We also
      provide strong, initial evidence that the ability of high Ca2+ levels to mitigate
      heat stress effects results from shifts in meristematic activity. Total foliar
      mass and leaf area were essentially unaffected by Ca2+ level under control
      temperatures. Under heat stress, leaf area was reduced to about 5% of the control
      at 5 and 25 &mgr;M Ca but to only 70% of the control at 125 and 600 &mgr;M Ca.
      Likewise, total foliar mass was reduced under heat stress to about 30% of the
      control at 5 and 25 &mgr;M Ca but total foliar mass was greater under heat stress
      than control conditions at 125 and 600 &mgr;M Ca. This increase at higher Ca2+
      concentrations was due primarily to axillary shoot growth. Anatomical studies of
      leaves grown under heat stress show that cell expansion was impaired by heat
      stress and this impairment was overcome by increasing root zone calcium levels.
      These results provide insight into the mechanism by which root zone Ca2+ may
      modulate plant response to heat stress.

PMID- 12010475
TI  - Ethanol sensitivity of rice and oat coleoptiles.
AB  - The ability to avoid the ethanol-induced injury was evaluated in rice (Oryza
      sativa L.) and oat (Avena sativa L.) coleoptiles. The growth of the rice and oat
      coleoptiles was inhibited by ethanol exogenously applied at concentrations
      greater than 200 and 30 mM, respectively. At 300 mM ethanol, oat coleoptiles were
      brown and flaccid but rice coleoptiles did not show any visible symptoms of
      toxicity. The acetaldehyde level in rice and oat coleoptiles was increased by
      exogenously applied ethanol and the increases were greater in oat than in rice
      coleoptiles under aerobic and anaerobic conditions. At 300 mM ethanol, the
      acetaldehyde concentrations in the rice and oat coleoptiles were 46 and 87 nmol g
      1 FW under aerobic conditions, respectively, and 52 and 124 nmol g-1 FW under
      anaerobic conditions, respectively. The activity of alcohol dehydrogenase (ADH;
      EC 1.1.1.1) in the direction of ethanol to acetaldehyde was greater in oat than
      in rice coleoptiles and ADH protein in oat coleoptiles was more induced by
      exogenously applied ethanol than that in rice coleoptiles. These results suggest
      that in vivo conversion rate of ethanol to acetaldehyde by ADH is lower in rice
      than oat coleoptiles, which may be one of the reasons that ethanol sensitivity of
      rice is much lower than that of oat coleoptiles. The great ability of rice to
      avoid the ethanol-induced injuries may contribute its anoxia tolerance when
      glycolysis and ethanolic fermentation replace the Krebs cycle as the main source
      of energy under anaerobic conditions.

PMID- 12010476
TI  - Expression of nitrate transporter genes in tomato colonized by an arbuscular
      mycorrhizal fungus.
AB  - PCR amplifications using tomato DNA and degenerate oligonucleotide primers
      allowed identification of a new putative nitrate transporter, termed NRT2;3. Its
      sequence showed typical motifs of a high affinity nitrate transporter of the
      Major Facilitator Superfamily (MFS). The formation of its mRNA was positively
      controlled by nitrate, and negatively by ammonium, but not by glutamine. In situ
      hybridization experiments showed that this transporter was mainly expressed in
      rhizodermal cells. Results from expression studies with two other nitrate
      transporters, LeNRT1;1 and LeNRT2;1, were essentially in accord with data of the
      literature. In roots colonized by the arbuscular mycorrhizal fungus Glomus
      intraradices Sy167, transcript formation of NRT2;3 extended to the inner cortical
      cells where the fungal structures, arbuscules and vesicles, were concentrated.
      Northern analyses indicated that the expression of only NRT2;3 among the
      transporters assayed was higher in AMF colonized tomato roots than in non
      colonized controls. AMF-colonization caused a significant expression of a nitrate
      reductase gene of G. intraradices. The results may mean that AMF-colonization
      positively affects nitrate uptake from soil and nitrate allocation to the plant
      partner, probably mediated preferentially by LeNRT2;3. In addition, part of the
      nitrate taken up is reduced by the fungal partner itself and may then be
      transferred, when in excess, as glutamine to the plant symbiotic partner.

PMID- 12010477
TI  - Aphid (Sitobion yakini) investigation suggests thin-walled sieve tubes in barley
      (Hordeum vulgare) to be more functional than thick-walled sieve tubes.
AB  - Barley, like most other grasses that have been studied, contains two kinds of
      sieve tube. The first formed are called thin-walled sieve tubes because of their
      thin wall compared to the late-formed, and are associated with companion cells.
      The late-formed are thick-walled sieve tubes, which differentiate next to the
      metaxylem vessels and lack companion cells. Aphid (Sitobion yakini (Eastop)
      feeding was studied using light microscopy to determine if they preferentially
      feed from thin- or thick-walled sieve tubes in the barley leaf. Penetration of
      the stylets through the leaf epidermis and mesophyll was largely intercellular,
      becoming partly intercellular and, partly, intracellular inside the vascular
      bundle. Sixteen of 19 pairs of stylets (84%), and 293 of 317 (92%) stylet tracks
      terminated at the thin-walled sieve tubes, suggesting that Sitobion yakini feeds
      preferentially on the thin-walled sieve tubes which seem to be more attractive to
      the aphid. These thin-walled sieve tubes are thus probably the most functional in
      terms of phloem loading and transport.

PMID- 12010478
TI  - Endosperm-specific expression of green fluorescent protein driven by the hordein
      promoter is stably inherited in transgenic barley (Hordeum vulgare) plants.
AB  - The expression of green fluorescent protein (GFP) and its inheritance were
      studied in transgenic barley (Hordeum vulgare L.) plants transformed with a
      synthetic green fluorescent protein gene [sgfp(S65T)] driven by either a rice
      actin promoter or a barley endosperm-specific d-hordein promoter. The gene
      encoding phosphinothricin acetyltransferase (bar), driven by the maize ubiquitin
      promoter and intron, was used as a selectable marker to identify transgenic
      tissues. Strong GFP expression driven by the rice actin promoter was observed in
      callus cells and in a variety of tissues of T0 plants transformed with the
      sgfp(S65T)-containing construct. GFP expression, driven by the rice actin
      promoter, was observed in 14 out of 17 independent regenerable transgenic callus
      lines; however, expression was gradually lost in T0 and later generation progeny
      of diploid lines. Stable GFP expression was observed in T2 progeny from only 6
      out of the 14 (43%) independent GFP-expressing callus lines. Four of the 8 lines
      not expressing GFP in T2 progeny, lost GFP expression during T0 plant
      regeneration from calli; one lost GFP expression in the transition from the T0 to
      T1 generations and three lines were sterile. Similarly, expression of bar driven
      by the maize ubiquitin promoter was lost in T1 progeny; only 21 out of 26 (81%)
      independent lines were Basta-resistant. In contrast to actin-driven expression,
      GFP expression driven by the d-hordein promoter exhibited endosperm-specificity.
      All seven lines transformed with d-hordein-driven GFP (100%) expressed GFP in the
      T1 and T2 generations, regardless of ploidy levels, and expression segregated in
      a Mendelian fashion. We conclude that the sgfp(S65T) gene was successfully
      transformed into barley and that GFP expression driven by the d-hordein promoter
      was more stable in its inheritance pattern in T1 and T2 progeny than that driven
      by the rice actin promoter or the bar gene driven by the maize ubiquitin
      promoter.

PMID- 12010479
TI  - Pyrimidine nucleotide and nucleic acid synthesis in embryos and megagametophytes
      of white spruce (Picea glauca) during germination.
AB  - Pyrimidine nucleotide synthesis was investigated in isolated germinating zygotic
      embryos and separated megagametophytes of white spruce by following the metabolic
      fate of 14C-labelled orotic acid, uridine, and uracil, as well as by measuring
      the activities of the major enzymes participating in nucleotide synthesis. The
      rate of nucleic acid synthesis in these tissues was also examined by tracer
      experiments and autoradiographic studies conducted with labelled thymidine, and
      by conventional light microscopy. From our results, it emerges that changes in
      the contribution of the de novo and salvage pathways of pyrimidines play an
      important role during the initial stages of zygotic embryo germination.
      Preferential utilization of uridine for nucleic acid synthesis, via the salvage
      pathway, was observed at the onset of germination, before the restoration of a
      fully functional de novo pathway. Similar metabolic changes, not observed in the
      gametophytic tissue, were also documented in somatic embryos previously. These
      alterations of the overall pyrimidine metabolism may represent a strategy for
      ensuring the germinating embryos with a large nucleotide pool. Utilization of 14C
      thymidine for nucleic acid synthesis increased in both dissected embryos and
      megagametophytes during germination. Autoradiographic and light microscopic
      studies indicated that soon after imbibition, DNA synthesis was preferentially
      initiated along the embryonic axis, especially in the cortical cells. Apical
      meristem reactivation was a later event, and the root meristem became activated
      before the shoot meristem. Taken together, these results indicate that precise
      changes in nucleotide and nucleic acid metabolism occur during the early phases
      of embryo germination.

PMID- 12010481
TI  - Erratum.

PMID- 12010480
TI  - Influence of CO2 and sucrose on photosynthesis and transpiration of Actinidia
      deliciosa explants cultured in vitro.
AB  - Explants of Actinidia deliciosa Chev. Liang and Ferguson var. Hayward were
      cultured in controlled CO2 atmospheres in the presence of different sucrose
      concentrations. Organogenesis was measured after 45 days in explants from the
      different assays, and quantification of photosynthesis, transpiration,
      chlorophylls, RUBISCO and total soluble protein content was performed in leaves
      from the different treatments. The best results were those of explants cultured
      at 600 &mgr;mol CO2 mol-1 on 20 g l-1 of sucrose for the first 20 days and then
      transferred to sucrose-free medium until the end of the culture period.
      Increasing CO2 to 2000 &mgr;mol CO2 mol-1 in the atmosphere of the culture vessel
      reduced all the parameters studied. Photosynthesis of autotrophically developed
      explants trebled that of the reference heterotrophic explants, as there was an
      apparent inverse relationship between photosynthesis and transpiration.
      Photosynthesis was saturated at 300 &mgr;mol m-2 s-1 PPFD and 600 &mgr;mol CO2
      mol-1. Chlorophylls and RUBISCO presented differences between treatments, mainly
      between different CO2 concentrations, with the highest values in autotrophically
      cultured explants. Explants grown at 2000 &mgr;mol CO2 mol-1 showed the lowest
      RUBISCO/Prots ratio, probably due to negative adaptation of RUBISCO to long-term
      high CO2. In short, explants grown in a controlled microenvironment, with
      increased CO2 and under autotrophic conditions, developed wholly functional
      photosynthetic apparatus well prepared to be transferred to ex vitro conditions,
      which has many advantages in micropropagation.

PMID- 12010482
TI  - Progesterone fails to modulate Toxoplasma gondii replication in the RAW 264.7
      murine macrophage cell line.
AB  - Cell mediated immunity is very important for host defence against intracellular
      pathogens and many studies have shown the role of the production of nitric oxide
      (NO) by interferon (IFN)-gamma/lipopolysaccharide (LPS)-activated macrophages. As
      the progesterone level increases during pregnancy in mammals, and as previous
      studies have shown that progesterone inhibits inducible nitric oxide synthase
      (iNOS) expression and NO production, we aimed to investigate whether progesterone
      might modulate intracellular replication of Toxoplasma gondii in macrophages. Our
      results showed that progesterone does not influence T. gondii replication in non
      activated RAW 264.7 cells, and although progesterone inhibits NO production
      induced by IFN-gamma/LPS, we observed that it fails to restore the growth of T.
      gondii blocked by IFN-gamma/LPS. After discussing the reasons for this apparent
      discrepancy, we concluded that progesterone has no direct effect on the
      macrophage response. The real effect of the sex steroids in T. gondii infection
      and their implication in clinical toxoplasmosis therefore need to be investigated
      further to involve wider mechanisms of the immune system.

PMID- 12010483
TI  - Comparative efficacy of the Schistosoma mansoni nucleic acid vaccine, Sm23,
      following microseeding or gene gun delivery.
AB  - Sm23 is an integral membrane protein expressed widely in the human parasitic worm
      Schistosoma mansoni. Sm23 has already been shown to elicit protective immune
      responses following immunization with peptides or DNA constructs. In this study,
      we evaluated the immunogenicity and the protective efficacy of the Sm23 DNA
      vaccine using two different intradermal DNA delivery methods: microseeding and
      gene gun. Using both techniques, all mice immunized with the Sm23-pcDNA construct
      generated Sm23-specific immunoglobulin (Ig)G antibody, while mice immunized with
      the control plasmid, pcDNA, did not. Antibody isotypes analysis revealed that
      microseeding elicited mainly IgG2a and IgG2b antibodies, with relatively low
      levels of IgG1 and IgG3. The relative IgG1/IgG2a ratio was 0.03, indicative of a
      Th1 type immune response. In contrast, gene gun immunization resulted in
      significantly higher levels of IgG1 and IgG3. The relative IgG1/IgG2a ratio in
      this case was 11, indicative of a Th2 type immune response. No significant
      difference in the levels of IgG2b was observed. Coimmunization with plasmid DNA
      encoding either interleukin (IL)-12 or IL-4 by microseeding did not affect the
      levels of IgG1, while the levels of IgG2a and IgG2b were reduced. On the other
      hand, the levels of IgG3 were significantly increased by IL-4, but unchanged by
      IL-12. Importantly, in all experiments, the Sm23-pcDNA vaccine provided
      statistically significant levels of protection against challenge infection.
      Microseeding immunizations resulted in higher levels of protection (31-34%
      protection) than gene gun immunization (18% protection). This suggests that the
      Th1 type immune response elicited by microseeding immunization was responsible
      for the higher protection levels. However, the protective effect of the vaccine
      was not affected by coadministering plasmids encoding either IL-12 or IL-4 using
      the microseeding technique.

PMID- 12010484
TI  - Protection studies with recombinant excretory/secretory proteins of Haemonchus
      contortus.
AB  - The efficacy of two recombinant proteins of Haemonchus contortus was studied in
      both adult sheep and young lambs. These 15 and 24 kDa excretory/secretory
      proteins were given combined, either supplemented or not with a glycan-rich
      insect cell extract. In 9-month-old sheep (trial 1), faecal egg output and worm
      burden were reduced by 49% and 55%, respectively, after vaccination with
      rec15/24, and by 46% and 65% after vaccination with rec15/24 and glycan extract.
      No reduction in egg output or number of worms was found in young lambs using the
      above recombinant proteins plus glycan-rich extract (trial 2). When trial 1 was
      repeated (trial 3), the protection could not be reproduced, possibly due to
      differences in batches of recombinant proteins. In all sheep, independent of
      their age, rec15/24-specific immunoglobulin (Ig)G1 and IgA titres were present,
      but 9-month-old protected sheep had significantly higher IgA titres than the
      lambs. Addition of glycans resulted in lower rec15/24-specific IgG1 and IgA in 9
      month-old sheep after challenge. This did not affect the level of protection. A
      significant negative correlation was found between IgA and worm numbers in
      protected sheep immunized with rec15/24 supplemented with glycans. Total IgE and
      rec15/24 specific IgE titres were low. The number of eosinophils, mast cells,
      sheep mast cell protease (SMCP)+ cells and IgA+ cells did not differ between the
      protected and unprotected sheep, but the lambs had significantly fewer mast cells
      independent of their immunization.

PMID- 12010485
TI  - A comparison of local and peripheral parasite-specific antibody production in
      different strains of mice infected with Trichuris muris.
AB  - The serum parasite-specific antibody responses of different mouse strains
      infected with Trichuris muris reflect the nature of the T-helper response mounted
      by the host, in that resistant Th2-responding strains, such as BALB/K, produce
      immunoglobulin (Ig)G1 and susceptible predominantly Th1-responding strains, such
      as AKR, produce IgG2a and IgG1. However, the kinetics of antibody production in
      the sera, as determined by enzyme-linked immunosorbent assay, do not reflect
      infection status in that resistant strains can expel their worm burdens before
      antibodies are detectable in the sera. Here, we show that parasite-specific
      antibody production by in vitro lipopolysaccharide-stimulated mesenteric lymph
      node cells (MLN) not only correlate with serum antibody isotypes, but also follow
      expulsion kinetics. Additionally, the antibody levels seen locally match changes
      in absolute B220+ cell numbers in the MLN (determined by flow cytometry) and
      changes in MLN parasite-specific plasma cells in the MLN (determined by ELISPOT).
      These results show that B cell responses are tightly regulated locally in both
      resistant and susceptible strains of mice infected with T. muris.

PMID- 12010486
TI  - Effects of irradiation on Plasmodium falciparum sporozoite hepatic development:
      implications for the design of pre-erythrocytic malaria vaccines.
AB  - Immunization with irradiation-attenuated Plasmodium sporozoites confer protection
      against live sporozoite challenge. Protection relies primarily on cytotoxic
      lymphocyte activity against infected hepatocytes, and is suppressed when
      sporozoites are over-irradiated. Here, we demonstrate that over-irradiated (25-30
      krad) Plasmodium falciparum sporozoites invade human hepatocytes and transform
      into uninucleate liver-trophozoites with the same efficiency as non-irradiated
      and irradiation-attenuated (12-15 krad) sporozoites. Since hepatocytes infected
      with over-irradiated non-protective sporozoites are likely to express sporozoite
      derived peptide/major histocompatibility complex class I molecules on their
      surface, our results strongly suggest that sporozoite proteins are not the main
      immunogens involved in protection, and thus may not per se constitute proper
      malaria vaccine candidates.

PMID- 12010487
TI  - How do membrane proteins sense water stress?
AB  - Maintenance of cell turgor is a prerequisite for almost any form of life as it
      provides a mechanical force for the expansion of the cell envelope. As changes in
      extracellular osmolality will have similar physicochemical effects on cells from
      all biological kingdoms, the responses to osmotic stress may be alike in all
      organisms. The primary response of bacteria to osmotic upshifts involves the
      activation of transporters, to effect the rapid accumulation of osmoprotectants,
      and sensor kinases, to increase the transport and/or biosynthetic capacity for
      these solutes. Upon osmotic downshift, the excess of cytoplasmic solutes is
      released via mechanosensitive channel proteins. A number of breakthroughs in the
      last one or two years have led to tremendous advances in our understanding of the
      molecular mechanisms of osmosensing in bacteria. The possible mechanisms of
      osmosensing, and the actual evidence for a particular mechanism, are presented
      for well studied, osmoregulated transport systems, sensor kinases and
      mechanosensitive channel proteins. The emerging picture is that intracellular
      ionic solutes (or ionic strength) serve as a signal for the activation of the
      upshift-activated transporters and sensor kinases. For at least one system, there
      is strong evidence that the signal is transduced to the protein complex via
      alterations in the protein-lipid interactions rather than direct sensing of ion
      concentration or ionic strength by the proteins. The osmotic downshift-activated
      mechanosensitive channels, on the other hand, sense tension in the membrane but
      other factors such as hydration state of the protein may affect the equilibrium
      between open and closed states of the proteins.

PMID- 12010488
TI  - Structural basis of tropism of Escherichia coli to the bladder during urinary
      tract infection.
AB  - The first step in the colonization of the human urinary tract by pathogenic
      Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at
      the tip of type 1 pili, to the bladder epithelium. We elucidated
      crystallographically the interactions of FimH with D-mannose. The unique site
      binding pocket occupied by D-mannose was probed using site-directed mutagenesis.
      All but one of the mutants examined had greatly diminished mannose-binding
      activity and had also lost the ability to bind human bladder cells. The binding
      activity of the mono-saccharide D-mannose was delineated from this of mannotriose
      (Man(alpha 1-3)[Man(alpha 1-6)]Man) by generating mutants that abolished D
      mannose binding but retained mannotriose binding activity. Our structure/function
      analysis demonstrated that the binding of the monosaccharide alpha-D-mannose is
      the primary bladder cell receptor for uropathogenic E. coli and that this event
      requires a highly conserved FimH binding pocket. The residues in the FimH mannose
      binding pocket were sequenced and found to be invariant in over 200 uropathogenic
      strains of E. coli. Only enterohaemorrhagic E. coli (EHEC) possess a sequence
      variation within the mannose-binding pocket of FimH, suggesting a naturally
      occurring mechanism of attenuation in EHEC bacteria that would prevent them from
      being targeted to the urinary tract.

PMID- 12010489
TI  - Uptake and intracellular transportation of a bacterial surface protein in
      lymphoid cells.
AB  - Some strains of the human pathogen Streptococcus pyogenes express a surface
      protein called protein H, which is released from the streptococcal surface by a
      cysteine proteinase produced by the bacteria. Here, we find that soluble protein
      H binds to the surface of lymphocytes and granulocytes, and that the molecule is
      taken up by lymphocytes and transported to the perinuclear region. The
      translocation over the cell membrane is rapid, and the uptake and intracellular
      transportation is not dependent on actin polymerization. Protein H could be
      immunoprecipitated from cell extracts and nuclear preparations of lymphocytes,
      and analysis of molecular interactions between protein H and proteins of
      different cellular compartments demonstrated a binding to nucleophosmin/ B23, a
      protein known to shuttle between the cytoplasm and the nucleus, and to the
      nuclear proteins SET and hnRNP A2/B1. Nucleophosmin/B23 was co-immunoprecipitated
      with protein H from cell and nuclear extracts, and binding experiments, including
      kinetic analyses, suggest that protein H dissociating from nucleophosmin/B23
      complexes in the perinuclear region or in the nucleus binds to proteins SET and
      hnRNP A2/B1. Finally, the uptake and intracellular transportation of protein H
      was found to result in a cytostatic effect on B and T lymphocytes.

PMID- 12010490
TI  - Bacterial conjugative transfer: visualization of successful mating pairs and
      plasmid establishment in live Escherichia coli.
AB  - We used the LacO/GFP-LacI system to label and visualize the IncP beta plasmid
      R751 fluorescently during conjugative transfer between live donor and recipient
      bacteria. Comparisons of R751 in conjugative and non-conjugative conditions have
      allowed us to identify key localizations and movements associated with the
      initiation of conjugative transfer in the donor and the establishment of R751 in
      the recipient. A survey of successful mating pairs demonstrates that close
      physical contact between donor and recipient bacteria is required for DNA
      transfer and that regions of intimate contact can occur at any location on the
      donor or recipient cell membrane. The transferred DNA is positioned at the
      characteristic centre or quarter-cell position after conversion to a double
      stranded molecule in the recipient cell. Initial duplication of plasmids often
      results in an asymmetric distribution of plasmid foci. Symmetric localization
      (either at centre or at 1/4 and 3/4 cell lengths) occurs only after a significant
      lag, presumably reflecting the time required to synthesize the plasmid-encoded
      partitioning proteins.

PMID- 12010491
TI  - Bacteriophage control of Shiga toxin 1 production and release by Escherichia
      coli.
AB  - The stx genes of many Shiga toxin-encoding Escherichia coli (STEC) strains are
      encoded by prophages of the lambda bacteriophage family. In the genome of the
      Stx1-encoding phage H-19B, the stx(1)AB genes are found approximately 1 kb
      downstream of the late phage promoter, p(R)', but are known to be regulated by
      the associated iron-regulated promoter, p(Stx1). Growth of H-19B lysogens in low
      iron concentrations or in conditions that induce the prophage results in
      increased Stx1 production. Although the mechanism by which low iron concentration
      induces Stx1 production is well understood, the mechanisms by which phage
      induction enhances toxin production have not been extensively characterized. The
      studies reported here identify the factors that contribute to Stx1 production
      after induction of the H-19B prophage. We found that replication of the phage
      genome, with the associated increase in stx(1)AB copy number, is the most
      quantitatively important mechanism by which H-19B induction increases Stx1
      production. Three promoters are shown to be involved in stx(1)AB transcription
      after phage induction, the iron-regulated p(Stx1) and the phage-regulated p(R)
      and p(R)' promoters, the relative importance of which varies with environmental
      conditions. Late phage transcription initiating at the p(R)' promoter, contrary
      to previous findings in the related Stx2-encoding phage phi 361, was found to be
      unnecessary for high-level Stx1 production after phage induction. Finally, we
      present evidence that phage-mediated lysis regulates the quantity of Stx1
      produced by determining the duration of Stx1 accumulation and provides a
      mechanism for Stx1 release. By amplifying stx(1)AB copy number, regulating
      stx(1)AB transcription and allowing for Stx1 release, the biology of the Stx
      encoding phages contributes greatly to the production of Stx, the principal
      virulence factor of STEC.

PMID- 12010492
TI  - ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of
      Escherichia coli gyrase.
AB  - Broad-host-range plasmid RK2 encodes a post-segregational killing system, parDE,
      which contributes to the stable maintenance of this plasmid in Escherichia coli
      and many distantly related bacteria. The ParE protein is a toxin that inhibits
      cell growth, causes cell filamentation and eventually cell death. The ParD
      protein is a specific ParE antitoxin. In this work, the in vitro activities of
      these two proteins were examined. The ParE protein was found to inhibit DNA
      synthesis using an E. coli oriC supercoiled template and a replication-proficient
      E. coli extract. Moreover, ParE inhibited the early stages of both chromosomal
      and plasmid DNA replication, as measured by the DnaB helicase- and gyrase
      dependent formation of FI*, a highly unwound form of supercoiled DNA. The
      presence of ParD prevented these inhibitory activities of ParE. We also observed
      that the addition of ParE to supercoiled DNA plus gyrase alone resulted in the
      formation of a cleavable gyrase-DNA complex that was converted to a linear DNA
      form upon addition of sodium dodecyl sulphate (SDS). Adding ParD before or after
      the addition of ParE prevented the formation of this cleavable complex. These
      results demonstrate that the target of ParE toxin activity in vitro is E. coli
      gyrase.

PMID- 12010493
TI  - The cyanobacterial phytochrome Cph2 inhibits phototaxis towards blue light.
AB  - We analysed the effects of inactivation of the phytochrome genes cph1 and cph2 on
      the phototactic migration of the cyanobacterium Synechocystis sp. PCC 6803 under
      different light qualities. Motility towards white, green, red and far red light
      was not altered in several independently raised cph1, cph2 and cph1/cph2 double
      mutants. Blue light (lambda = 400-500 nm) did not induce motility in wild-type
      and cph1 mutant cells, whereas cph2 and cph1/cph2 double mutants moved towards
      the blue light. Inhibition of the photosynthetic electron transport by DCMU
      influenced the motility of cph2 mutants under blue light, but not under white,
      red and far red light. RNA blot hybridizations did not indicate an altered
      transcript accumulation of the pilin-encoding pilA1 gene under blue light. We
      propose that the Cph2 protein is part of a light-stimulated signal transduction
      chain inhibiting the movement of Synechocystis sp. PCC 6803 cells towards blue
      light.

PMID- 12010494
TI  - The Pneumocystis carinii drug target S-adenosyl-L-methionine:sterol C-24 methyl
      transferase has a unique substrate preference.
AB  - Pneumocystis is an opportunistic pathogen that can cause pneumonitis in
      immunodeficient people such as AIDS patients. Pneumocystis remains difficult to
      study in the absence of culture methods for luxuriant growth. Recombinant protein
      technology now makes it possible to avoid some major obstacles. The P. carinii
      expressed sequence tag (EST) database contains 11 entries of a sequence encoding
      a protein homologous to S-adenosyl-L-methionine (SAM):C-24 sterol methyl
      transferase (SMT), suggesting high activity of this enzyme in the organism. We
      sequenced the erg6 cDNA, identified the putative peptide motifs for the sterol
      and SAM binding sites in the deduced amino acid sequence and expressed the
      protein in Escherichia coli. Unlike SAM:SMT from other organisms, the P. carinii
      enzyme had higher affinities for lanosterol and 24-methylenelanosterol than for
      zymosterol, the preferred substrate in other fungi. Cycloartenol was not a
      productive substrate. With lanosterol and 24-methylenelanosterol as substrates,
      the major reaction products were 24-methylenelanosterol and pneumocysterol
      respectively. Thus, the P. carinii SAM:SMT catalysed the transfer of both the
      first and the second methyl groups to the sterol C-24 position, and the substrate
      preference was found to be a unique property of the P. carinii SAM:SMT. These
      observations, together with the absence of SAM:SMT among mammals, further support
      the identification of sterol C-24 alkylation reactions as excellent targets for
      the development of drugs specifically directed against this pathogen.

PMID- 12010495
TI  - The effect of genomic position on reversion of a lac frameshift mutation
      (lacIZ33) during non-lethal selection (adaptive mutation).
AB  - In a system described by Cairns and Foster, starvation of a particular leaky lac
      mutant (lacIZ33) in the presence of lactose appears to direct mutation in non
      growing cells to sites that allow growth (adaptive mutation). This behaviour
      requires that the lac operon be located on an F' plasmid. This position effect
      was investigated by placing the mutant lac operon at many sites in the genome of
      Salmonella enterica (Typhimurium; LT2) and testing reversion behaviour. Genomic
      position did not affect reversion during non-selective growth. When lac was at
      any of 550 chromosomal sites, starvation caused little or no enhancement of
      reversion. In the 28 strains with the lac on Salmonella's conjugative plasmid
      (pSLT), selection enhanced reversion strongly, just as seen for strains with lac
      on an F' plasmid. In 46 strains, the lac operon was inserted within a small
      chromosomal duplication, and selection stimulated RecA-dependent partial
      reversion by simple amplification (about 8x) of the mutant lac region. The
      position of lac on a conjugative plasmid is important to reversion because it
      allows more frequent gene duplication and amplification. These events are central
      to growth and reversion under selection because they increase the number of
      replicating lac alleles within each developing revertant clone.

PMID- 12010496
TI  - Multiple mechanisms for the activation of human platelet aggregation by
      Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine
      aspartate repeat protein SdrE and protein A.
AB  - The ability of Staphylococcus aureus cells to induce platelet aggregation has
      long been recognized. However, despite several attempts to identify the
      mechanisms involved in this interaction, the nature of the bacterial receptors
      required remains poorly understood. Using genetic manipulation, this study for
      the first time provides clear evidence that several S. aureus surface proteins
      participate in the inter-action with platelets. Mutants of S. aureus strain
      Newman lacking one or more surface proteins were tested for their ability to
      stimulate platelet aggregation. This approach was complemented by the expression
      of a number of candidate proteins in the non-aggregating Gram-positive bacterium
      Lacto-coccus lactis. S. aureus-induced aggregation was monophasic and was
      dependent on the platelet receptor GPIIb/IIIa. The fibrinogen-binding proteins,
      clumping factors A and B and the serine-aspartate repeat protein SdrE could each
      induce aggregation when expressed in L. lactis. Although protein A expressed in
      L. lactis was not capable of inducing aggregation independently, it enhanced the
      aggregation response when expressed on the surface of S. aureus. Thus, S. aureus
      has multiple mechanisms for stimulating platelet aggregation. Such functional
      redundancy suggests that this phenomenon may be important in the pathogenesis of
      invasive diseases such as infective endocarditis.

PMID- 12010497
TI  - Regulatory network of lipopolysaccharide O-antigen biosynthesis in Yersinia
      enterocolitica includes cell envelope-dependent signals.
AB  - Lipopolysaccharide (LPS) is a glycolipid present in the outer membrane of all
      Gram-negative bacteria, and it is one of the signature molecules recognized by
      the receptors of the innate immune system. In addition to its lipid A portion
      (the endotoxin), its O-chain polysaccharide (the O-antigen) plays a critical role
      in the bacterium-host interplay and, in a number of bacterial pathogens, it is a
      virulence factor. We present evidence that, in Yersinia enterocolitica serotype
      O:8, a complex signalling network regulates O-antigen expression in response to
      temperature. Northern blotting and reporter fusion analyses indicated that
      temperature regulates the O-antigen expression at the transcriptional level.
      Promoter cloning showed that the O-antigen gene cluster contains two
      transcriptional units under the control of promoters P(wb1) and P(wb2). The
      activity of both promoters is under temperature regulation and is repressed in
      bacteria grown at 37 degrees C. We demonstrate that the RosA/RosB efflux
      pump/potassium antiporter system and Wzz, the O-antigen chain length determinant,
      are indirectly involved in the regulation mainly affecting the activity of
      promoter P(wb2). The rosAB transcription, under the control of P(ros), is
      activated at 37 degrees C, and P(wb2) is repressed through the signals generated
      by the RosAB system activation, i.e. decreased [K+] and increased [H+]. The wzz
      transcription is under the control of P(wb2), and we show that, at 37 degrees C,
      overexpression of Wzz downregulates slightly the P(wb1) and P(wb2) activities and
      more strongly the P(ros) activity, with the net result that more O-antigen is
      produced. Finally, we demonstrate that overexpression of Wzz causes membrane
      stress that activates the CpxAR two-component signal transduction system.

PMID- 12010498
TI  - Differential gene expression in Entamoeba histolytica isolated from amoebic liver
      abscess.
AB  - The majority of human infections with the intestinal protozoan parasite Entamoeba
      histolytica remain asymptomatic. In a small proportion of infections, however, E.
      histolytica trophozoites penetrate the intestinal mucosa and disseminate to other
      organs, most commonly to the liver, where they induce abscess formation. It is
      believed that the ability of E. histolytica trophozoites to destroy host tissues
      and to survive within the liver is accomplished by a strong adaptive response,
      which requires the specific regulation of a number of amoeba proteins. Using
      differential display polymerase chain reaction (DD-PCR), we compared RNA
      expression between E. histolytica trophozoites isolated from liver abscesses of
      infected gerbils and those grown under normal culture conditions. A total of 3000
      cDNA-derived amplicons were compared between the two groups of amoebae, which
      were calculated to represent about one-third of all E. histolytica mRNA species
      (transcriptome). Among these, 55 were found to be specifically present or absent
      in abscess-derived amoebae, of which 42 were successfully cloned and sequenced.
      Database searches and Northern blot analyses revealed that the 42 amplicons
      correspond to 29 independent E. histolytica genes, of which at least seven are
      specifically upregulated and five are downregulated in abscess-derived amoebae.
      Specific expression of most of these genes was not simply the result of a heat
      shock response, which might be expected during abscess formation, as only five of
      the genes revealed an expression profile similar to that found in amoebae
      cultured under elevated temperatures. The two genes specifically downregulated in
      abscess-derived amoebae encode members of a family of so far unknown proteins,
      which contain repetitive stretches of sequences that are rich in lysine and
      glutamic acid residues. In contrast, a diverse set of genes is specifically
      upregulated, encoding ribosomal proteins (S30, L37A), cyclophilin, ferredoxin 2
      and GTP-binding protein RAB7D, supporting the notion that liver abscess formation
      requires the regulation and concerted action of a variety of amoeba proteins.
      These proteins are associated with stress response, signal transduction,
      regulation of transcription and vesicular trafficking. However, transcriptome
      analysis will not be sufficient to identify all proteins specifically upregulated
      during abscess formation, as at least an increase in the expression of actin was
      found to be regulated at the post-transcriptional level.

PMID- 12010499
TI  - The pivotal role of guanine phosphoribosyltransferase in purine salvage by
      Giardia lamblia.
AB  - Giardia lamblia is an anaerobic binucleate flagellated protozoan known to lack de
      novo synthesis of purine nucleotides. Our previous metabolic studies indicated
      two major parallel pathways mediated by adenine phosphoribosyltransferase (APRT)
      and guanine phosphoribosyltransferase (GPRT) that constitute the primary route of
      purine salvage in this organism. To verify further that these enzymes play a
      pivotal role in replenishing the purine ribonucleotide pool and are required for
      replicative growth of Giardia, a knock-out of GPRT gene expression in this
      organism was attempted. A hammerhead ribozyme flanked by two arms of GPRT
      antisense RNA (GPRZ) was designed, synthesized and found capable of cleaving a
      GPRT mRNA fragment in vitro at the designated site. GPRZ cDNA was then cloned
      into a viral vector pC631pac, derived from the genome of giardiavirus (GLV), and
      its transcript was introduced into GLV-infected Giardia trophozoites by
      electroporation. Stable transformants selected under increasing concentrations of
      puromycin displayed parallel increases in ribozyme levels and associated
      decreases in GPRT mRNA levels, GPRT enzyme activity and replicative cell growth
      to less than 10-20% of wild-type levels. Metabolite analyses showed specific
      depletion of the guanine ribonucleotide pools in parallel with slower cell
      growth. We conclude that GPRT plays an essential role in supplying guanine
      nucleotides required for growth and multiplication of Giardia, emphasizing its
      potential as a bona fide target for antigiardiasis chemotherapy.

PMID- 12010500
TI  - An accessory sec locus of Streptococcus gordonii is required for export of the
      surface protein GspB and for normal levels of binding to human platelets.
AB  - The translocation of proteins across the bacterial cell membrane is carried out
      by highly conserved components of the Sec system. Most bacterial species have a
      single copy of the genes encoding SecA and SecY, which are essential for
      viability. However, Streptococcus gordonii strain M99 encodes SecA and SecY
      homologues that are not required for viability or for the translocation of most
      exported proteins. The genes (secA2 and secY2) reside in a region of the
      chromosome required for the export of GspB, a 286 kDa cell wall-anchored protein.
      Loss of GspB surface expression is associated with a significant reduction in the
      binding of M99 to human platelets, suggesting that it may be an adhesin. Genetic
      analyses indicate that M99 has a second, canonical SecA homologue that is
      essential for viability. At least two other Gram-positive species, Streptococcus
      pneumoniae and Staphylococcus aureus, encode two sets of SecA and SecY
      homologues. One set is more similar to SecA and SecY of Escherichia coli, whereas
      the other set is more similar to SecA2 and SecY2 of strain M99. The conserved
      organization of genes in the secY2-secA2 loci suggests that, in each of these
      Gram-positive species, SecA2 and SecY2 may constitute a specialized system for
      the transport of a very large serine-rich repeat protein.

PMID- 12010501
TI  - Evidence for a partial redundancy of the fibronectin-binding proteins for the
      transfer of mycoloyl residues onto the cell wall arabinogalactan termini of
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis produces a series of major secreted proteins, the
      fibronectin-binding proteins (Fbps), also known as the antigen 85 complex, that
      are believed to play an essential role in the pathogenesis of tuberculosis
      through their mycoloyltransferase activity required for maintaining the integrity
      of the bacterial cell envelope. Four different fbp genes are found in the genome
      of M. tuberculosis, but the reason for the existence of these Fbps sharing the
      same substrate specificity in vitro in mycobacteria is unknown. We have shown
      previously that, in the heterologous host, Corynebacterium glutamicum, FbpA, FbpB
      and FbpC can all add mycoloyl residues to the cell wall arabinogalactan and that,
      in M. tuberculosis, the cell wall mycoloylation decreases by 40% when fbpC is
      knocked out. To investigate whether the remaining 60% mycoloylation came from the
      activity of FbpA and/or FbpB, fbpA- and fbpB-inactivated mutant strains were
      biochemically characterized and compared with the previously studied fbpC
      disrupted mutant. Unexpectedly, both mutants produced normally mycoloylated cell
      walls. Overproduction of FbpA, FbpB or FbpC, but not FbpD, in the fbpC
      inactivated mutant strain of M. tuberculosis restored both the cell wall-linked
      mycolate defect and the outer cell envelope permeability barrier property. These
      results are consistent with all three enzymes being involved in cell wall
      mycoloylation and FbpC playing a more critical role than the others or,
      alternatively, FbpC is able to compensate for FbpA and FbpB in ways that these
      enzymes cannot compensate for FbpC, pointing to a partial redundancy of Fbps. In
      sharp contrast, FbpD does not appear to be an active mycoloyltransferase enzyme,
      as it cannot complement the fbpC-inactivated mutant. Most importantly,
      application of Smith degradation to the cell walls of transformants demonstrated
      that the multiple Fbp enzymes are redundant rather than specific for the various
      arabinogalactan mycoloylation regions. Neither FbpA nor FbpB attaches mycoloyl
      residues to specific sites but, like FbpC, each enzyme transfers mycoloyl
      residues onto the four sites present in the arabinogalactan non-reducing end
      hexaarabinosides.

PMID- 12010503
TI  - Seroprevalence of hepatitis C markers among intravenous drug users in western
      European countries: a systematic review.
AB  - Currently, the most important risk factor for hepatitis C virus (HCV) infection
      in Europe is intravenous drug use. To establish a better insight into the
      epidemiology of hepatitis C among intravenous drug users (IVDUs) in western
      European countries a systematic review on the prevalence of hepatitis C markers
      and their determinants was performed. Reports were identified by searches on
      Medline and on the internet and by screening reference lists of selected papers.
      The prevalence rates of anti-HCV in western European IVDUs reported in the 66
      studies selected for analysis, ranged between 37 and 98%. No relation was found
      between prevalence rates and mean age, mean duration of intravenous drug use,
      geographical area, setting of the study, method of recruitment or the year(s) of
      collection of samples. Eleven studies concerning the prevalence of HCV-RNA in
      hepatitis C-infected IVDUs were selected for analysis. Prevalence rates ranged
      from 26 to 86%. Based on five studies, a statistically significant positive
      linear relation was found between the mean age of study population and the
      prevalence of HCV-RNA. Our analysis revealed considerable variation in prevalence
      rates of hepatitis C markers among IVDUs in western Europe. We found no
      conclusive explanation for this variability. Further research investigating the
      dynamics of the hepatitis C epidemic in IVDUs is necessary.

PMID- 12010504
TI  - Mapping and characterization of B cell linear epitopes in the conservative
      regions of hepatitis C virus envelope glycoproteins.
AB  - Forty-eight overlapping octapeptides covering highly conservative regions of E1
      and E2 hepatitis C virus (HCV) envelope proteins were synthesized and tested by
      ELISA against different groups of sera obtained from HCV-infected patients. All
      sera from patients with acute infection, except a single case of serum reactivity
      with the region HINRTALN, were nonreactive with any peptide. Sera obtained from
      chronic patients reacted with 12 peptides from five selected regions. Two
      immunodominant B epitopes were found, one being the precisely mapped antigenic
      site RMAWDM positioned inside the earlier shown immunodominant epitope from E1,
      and the second site, PALSTGLIH from E2, detected for the first time. New minor
      antigenic site was determined as PTDCFRKH from E2. We found only minor
      seroreactivity for one of the putative sites involved in CD81 binding, PYCWHYAP.

PMID- 12010505
TI  - Sequential analysis of hepatitis B virus core promoter and precore regions in
      cancer survivor patients with chronic hepatitis B before, during and after
      interferon treatment.
AB  - We analysed the hepatitis B virus (HBV) core-promoter (CP) and precore (PC)
      regions before, during and after interferon treatment in young Caucasian cancer
      survivors who had acquired HBV infection during chemotherapy for malignancies.
      Fourteen patients with chronic hepatitis B [hepatitis B e antigen (HBeAg) /HBV
      DNA positive] received alpha-2a interferon (IFN), 5 MU/m2 t.i.w. for 12 months.
      HBV CP and PC region sequences were analysed following polymerase chain reaction
      (PCR) amplification. Sera from responders were studied at: T(0) (before starting
      IFN), T(1) [at alanine aminotransferase (ALT) peak preceding HBeAg
      seroconversion], T(2) (at ALT normalization), T(3) (at end of IFN) and T(4) (at
      one year after IFN) and in nonresponders at time points T(0), T(3) and T(4).
      Amplified HBV-DNA was cloned and sequenced automatically. Six of 14 patients
      (43%) responded to IFN treatment. Five of the six (83%) responders displayed the
      double CP mutation A1762T/G1764A always in association with a T1753C change. None
      of the nonresponders showed these mutations at any time point. The G1896A change
      creating the PC stop codon mutation was never detected in any of the patients. In
      our cancer survivors, IFN-induced HBeAg/anti-HBe seroconversion appeared to
      correlate with CP mutations and was not influenced by previous chemotherapy.
      These mutations in addition to low HBV DNA levels and elevated ALT can be
      considered favourable factors of response to IFN-induced anti-HBe seroconversion.

PMID- 12010506
TI  - Matrix metalloproteinases and their inhibitors in acute viral hepatitis.
AB  - Matrix metalloproteases (MMPs) and their inhibitors are effector molecules
      involved in extracellular matrix remodelling. The serum profile for these
      proteolytic enzymes and their inhibitors during acute self-limiting viral
      hepatitis has not been studied. We therefore determined serum concentrations of
      MMP-1, MMP-3, MMP-2, MMP-9 and their inhibitors (tissue inhibitors of
      metalloproteinase) TIMP-1, TIMP-2 and alpha2 macroglobulin (AMG) in the serum of
      patients during the icteric stage of self-limiting acute viral hepatitis.
      Transforming growth factor-beta (TGF-beta) and interleukin (IL)-10, two cytokines
      involved in the regulation of MMPs and TIMPs were also assessed. Nineteen
      patients (12 men, seven women) with a mean age of 29.9 years (range 16-65 years)
      participated in the study. Fifteen had hepatitis B virus (HBV, two HCV and two
      HAV infection. The values of patients were compared with those obtained from 15
      blood donor controls (eight men, seven women), mean age 36.2 years (range 18-55
      years). Serum levels of TGF-beta, IL-10, MMP-1, MMP-3, MMP-2, MMP-9, TIMP-1 and
      TIMP-2 were assessed by ELISA. MMP-2 and MMP-9 were also measured by a zymogram
      protease assay. alpha2 macroglobulin (AMG) was measured by nephelometry. Compared
      with the healthy controls the mean serum concentrations of all MMPs were
      significantly decreased in the acute hepatitis patients. There was no difference
      in the serum concentration of TIMP-1 between patients and the controls. Serum
      levels of TIMP-2 (P < 0001), TGF-beta (P < 0.05), IL-10 (P < 0.001) and AMG (P <
      0001) were increased in patients compared to healthy controls. A statistically
      significant negative correlation by linear regression analysis was found between
      AMG and MMP-1 (P=0003). The decreased levels of MMPs observed, together with
      normal and increased levels of TIMP-1 and TIMP-2, may indicate an attempt to
      limit matrix degradation at this stage of disease resolution. The increased
      levels of the anti-inflammatory cytokines IL-10 and TGF-beta might be the
      underlying mechanism responsible for the above effect. AMG inhibition especially
      for MMP-1 may play an additional important role.

PMID- 12010507
TI  - Constrained genomic and conformational variability of the hypervariable region 1
      of hepatitis C virus in chronically infected patients.
AB  - We analysed the genomic and conformational variability of the hypervariable
      region 1 (HVR1) of the hepatitis C virus (HCV) to evaluate the importance of its
      biological role. A total of 865 genotype 1b HVR1 subclones were collected from
      serially sampled sera in 11 patients with chronic hepatitis C, four of whom
      received interferon therapy. Consequently, 169 distinct sequences were examined
      for amino acid substitutions as well as hydrophilic or hydrophobic profile at
      each amino acid position within HVR1. Secondary structure of HVR1 was also
      predicted by the method of Robson in 90 distinct sequences from eight patients,
      including three interferon-treated patients. Some positions within the HVR1 were
      invariable or nearly so as to amino acid substitution. Hydrophilic or hydrophobic
      residues exclusively predominated at several positions. These constrained amino
      acid replacement and hydrophilic or hydrophobic profiles were conserved
      irrespective of interferon therapy, though the frequency of amino acid
      replacement was greater at almost all amino acid positions within the HVR1 in
      interferon-treated patients. The quasispecies of HCV showed various secondary
      structures of HVR1, but many sequences seemed to have common characteristics.
      beta sheet conformations around both the N-terminus and position 20 (numbered
      from the NH2 terminus of E2 envelope glycoprotein), and/or coil structures around
      the C-terminus of HVR1 could be identified. These results suggest that HVR1 amino
      acid replacements are strongly constrained by a well-ordered structure, in spite
      of being tolerant to amino acid substitutions, and imply an important biological
      role of the HVR1 protein in HCV replication.

PMID- 12010508
TI  - Early detection of nonresponse to interferon plus ribavirin combination treatment
      of chronic hepatitis C.
AB  - We have investigated the value of early hepatitis C virus (HCV) RNA decline
      (DeltaHCV RNA) to predict response to combination therapy in 66 chronic hepatitis
      C patients treated with IFN-alpha2b (3 MU thrice weekly) and ribavirin (800 mg
      daily) for 12 months [25 sustained responders (SR) and 41 nonresponders or
      relapsers (NR)]. Serum HCV RNA was retrospectively measured in samples obtained
      at baseline and 4, 8 and 12 weeks after treatment onset, using a commercially
      available quantitative RT-PCR assay. At 4 weeks, serum HCV RNA had decreased a
      mean of 2.6 +/- 0.8 logs among SR as compared with only 0.5 +/- 0.8 logs in NR (P
      < 0.001), and was already undetectable (< 600 IU/mL) in 12 (48%) of the SR but in
      none of the NR. At 8 weeks, HCV RNA was undetectable in 21 SR and in 2 NR and
      mean DeltaHCV RNA were 4.2 +/- 1.3 and 0.8 +/- 1.0 logs, respectively (P <
      0.001). At week 12 all SR had undetectable HCV RNA as compared with only five NR
      (P < 0.001). Stepwise logistic regression analysis identified DeltaHCV RNA at 12
      weeks as the strongest predictor of sustained response. Receiver operating
      characteristic (ROC) curves of DeltaHCV RNA for sustained response prediction
      identified sensitivity peaks with 100% negative predictive value corresponding to
      DeltaHCV RNA > 1 log at 4 weeks, > 2 logs at 8 weeks and > 3 logs at 12 weeks.
      Our results show that early changes in the HCV RNA level may reliably identify
      patients having no chance of a sustained virological response during the first 3
      months of combination therapy, thus providing an excellent tool for optimizing
      antiviral treatment of chronic hepatitis C.

PMID- 12010509
TI  - Effect of virological response on post-treatment durability of lamivudine-induced
      HBeAg seroconversion.
AB  - Lamivudine-induced HBeAg seroconversion may not be durable in Korean patients
      with hepatitis B virus (HBV) infection. It is unknown whether virological
      response during lamivudine treatment affects the post-treatment outcome. We
      retrospectively analysed 124 consecutive HBeAg-positive chronic hepatitis B (CHB)
      patients treated with lamivudine. Lamivudine was given at a dose of 100 mg per
      day. HBV DNA levels in sera obtained before and during therapy were measured by
      the Digene Hybrid Capture II assay and Digene Ultrasensitive Hybrid Capture II
      assay, respectively. HBeAg seroconversion was achieved in 42 of the 124 patients
      (33.8%) treated with lamivudine. Mean duration of treatment in HBeAg
      seroconverters was 12.86 +/- 4.44 months. During the follow-up period, the
      cumulative relapse rates at 3 months and 6 months post-treatment in 42 patients
      with HBeAg seroconversion were 40.5% and 57.4%, respectively. Among 31
      seroconverted patients whose sera were available at the second month of
      treatment, HBV DNA remained at > 4.7 x 103 genomes/mL in 15 patients and
      decreased to < 4.7 x 103 genomes/mL in the remaining 16 patients. HBV DNA levels
      at the second month of treatment was not related with relapse after
      discontinuation of treatment (66.7% vs. 43.8%, P= 0.2). At the time of HBeAg
      seroconversion, HBV DNA remained at > 4.7 x 103 genomes/mL in five patients and
      decreased to < 4.7 x 103 genomes/mL in the remaining 37 patients. Relapse rates
      were increased in patients who remained at > 4.7 x 103 genomes/mL compared with
      patients with HBV DNA levels < 4.7 x 103 genomes/mL (100% vs. 51.4%, P < 0.001).
      Thus, monitoring of serum HBV DNA at the time of HBeAg seroconversion may be
      helpful for predicting relapse in patients with lamivudine-induced HBeAg
      seroconversion.

PMID- 12010510
TI  - Increased serum levels of macrophage inflammatory protein-3alpha in chronic viral
      hepatitis: prognostic importance of macrophage inflammatory protein-3alpha during
      interferon therapy in chronic hepatitis C.
AB  - Increased infiltration of lymphocytes and induction of damage and destruction of
      hepatocytes by these lymphocytes are characteristic features of chronic viral
      hepatitis. As chemokines attract lymphocytes to inflamed tissues, we studied
      macrophage inflammatory protein (MIP)-3alpha, a CC chemokine, in chronic viral
      hepatitis. The levels of MIP-3alpha were measured in the sera from 40 patients
      with chronic viral hepatitis and 30 control subjects by an enzyme-linked
      immunosorbent assay (detection limit of MIP-3alpha=7.8 pg/mL). The kinetics of
      MIP-3alpha were checked during interferon (IFN) therapy in 25 patients. The
      levels of MIP-3alpha in the sera were significantly higher in patients with
      chronic viral hepatitis (39.0 +/- 28.9 pg/mL) than control subjects (15.6 +/- 4.9
      pg/mL; P < 0.0001) and in patients with severe (49.6 +/- 49.2 pg/mL) and moderate
      degree of hepatitis (50.9 +/- 27.1 pg/mL) than in mild disease (16.0 +/- 6.8
      pg/mL; P < 0.05). A significant correlation was seen among serum MIP-3alpha
      levels with the levels of alanine aminotransferase (r=0.509, P < 0.0001),
      aspartate aminotransferase (r=0.505, P < 0.0001), and degrees of activity of
      hepatitis (r=0.592, P < 0.0001) and interface hepatitis (r=0.419, P=0.0066). The
      levels of MIP-3alpha were significantly increased in patients with hepatitis C 2
      weeks after the start of therapy in IFN-responders, but, remained almost
      unchanged in IFN-nonresponders. These findings might be important not only for
      the understanding of immunoptahogenesis of hepatocellular damage in chronic
      hepatitis (CH) patients but also for a therapeutic strategy to control the local
      immune response in the liver. A prognostic value of MIP-3alpha during IFN therapy
      in patients with chronic hepatitis C is also shown.

PMID- 12010511
TI  - Passive immunization of chronic hepatitis B patients on lamivudine therapy: a
      feasible issue?
AB  - In view of the limited efficacy of lamivudine monotherapy for chronic hepatitis B
      (HBV) infection, combination with other drugs seems logical. Intravenous
      neutralization of circulating HBsAg by specific hepatitis B immunoglobulin (HBIg)
      has been shown to protect hepatocytes against (re-)infection with HBV in the
      setting of liver transplantation and postexposure prophylaxis. Large controlled
      vaccination trials have revealed that HBV can be prevented by HBIg therapy in the
      majority of newborns after perinatal infection. A benefit of anti-HBs in HBV
      patients has so far only been investigated in three small studies. In this pilot
      study we investigated the effects of polyclonal i.v. HBIg (HepatectR, Biotest)
      administration in HBV-infected patients. Six liver biopsy-proven HBV-infected
      patients, all on lamivudine treatment and HBV DNA negative by PCR, were
      investigated. Pre-treatment HBsAg levels varied between 120 and 9760 ng/mL. On
      day 1, 10.000 IU HBIg was given, followed by 10.000 IU once, twice or three times
      on day 29. Long-term follow-up lasted at least 4 months. HBsAg and anti-HBs were
      measured quantitatively by standard MEIA and also by an experimental EIA. In
      vitro neutralization of HBsAg by Hepatect was mimicked in an 'inhibition in
      solution assay'. Complete neutralization of HBsAg by HBIg in vitro was possible,
      50% inhibition concentrations varied between 100 and 250 IU/L HBIg with HBsAg
      levels of 68 and 120 ng/mL. No HBIg-related side-effects were observed. In two
      patients with low pretreatment HBsAg levels HBsAg reached levels below the
      detection limit of the assay, which persisted a maximum of 31 and 7.5 h,
      respectively. Peak anti-HBs concentrations were 5100 and 4648 IU/L. In the other
      four patients, with higher pretreatment HBsAg levels, HBsAg concentrations in
      serum hardly changed. For the whole population, the drop in HBsAg did not reach
      statistical significance. However, in four of the six patients a further decrease
      in HBsAg [18%-66%] was observed. In conclusion, HBIg was well tolerated; however,
      efficacy was limited due to high HBsAg levels in spite of maximum inhibition of
      virion production. 'Neutralization' was achieved only in two patients with low
      HBsAg levels. Passive immunization in HBV-DNA negative patients is not a feasible
      option. This strategy seems only feasible if agents inhibiting both the
      production of viral proteins and Dane particles more selectively, become
      available.

PMID- 12010512
TI  - Relationship of clinical and virological factors with hepatitis activity in
      hepatitis B e antigen-negative chronic hepatitis B virus-infected patients.
AB  - To investigate the factors associated with active disease among hepatitis B
      surface antigen (HBsAg) positive/hepatitis B e antigen (HBeAg)-negative chronic
      hepatitis B virus (HBV) infection we studied chronic HBV infected patients who
      had undetectable HBeAg at the first visit. HBV DNA was determined by the cross
      linking assay (NAXCOR) and polymerase chain reaction (PCR). Mutations in the core
      promoter and precore regions and viral genotypes were studied. Clinical outcome
      of these patients were followed and categorized as: (i) relapse (ALT > 200 IU/L
      or three times the previous levels); (ii) active hepatitis (elevated ALT < 200
      IU/L with concomitant detectable HBV DNA); or (iii) remission. A total of eighty
      five patients were followed up for 5.5 +/- 1.0 years. At first visit, 31 (36.5%)
      patients had elevated ALT levels, 12 (14.1%) had measurable HBV DNA by the cross
      linking assay and 26 (30.6%) by PCR. Sixteen (18.8%) patients had hepatitis
      relapse, 13 (15.3%) had active hepatitis, and 56 (65.9%) remained in remission.
      Core promoter and precore stop codon mutants were found in 27 and 12 patients,
      respectively. Eleven and 20 had genotype B and C HBV, respectively. Initial
      elevated ALT and detectable HBV DNA were associated with active liver disease.
      Patient demographics, viral mutants or genotypes failed to predict disease
      activity. Hence, serum ALT and HBV DNA levels offer the best prediction of
      natural course of HBeAg-negative chronic HBV infection.

PMID- 12010513
TI  - Moderate alcohol intake increases fibrosis progression in untreated patients with
      hepatitis C virus infection.
AB  - Although excessive alcohol consumption in combination with hepatitis C virus
      (HCV) infection is known to increase the risk of liver cirrhosis, the effect of
      moderate alcohol intake remains to be elucidated. The aim of this study was to
      evaluate the effect of moderate alcohol consumption on fibrosis progression in
      HCV infection. A group of 78 patients with HCV infection and moderate alcohol
      consumption were analysed retrospectively. All patients had undergone two liver
      biopsies, with a median time between biopsies of 6.3 years, and had not received
      any antiviral therapy. Their lifetime drinking history was recorded. All patients
      except one had daily alcohol consumption below 40 g of ethanol (median 4.8 g/day,
      interquartile range 1.1-11.6 g/day) during the period between the biopsies. The
      patients whose liver fibrosis had deteriorated had a higher total alcohol
      consumption and higher drinking frequency between the biopsies. The degree of
      fibrosis progression was greater in patients with a total alcohol intake and
      drinking frequency above the median level for the group. A multiple logistic
      regression analysis showed that drinking frequency and time between biopsies were
      independently associated with fibrosis progression. Hence, even moderate alcohol
      intake seems to increase fibrosis progression in HCV-infected patients. From that
      point of view, total abstention ought to be recommended. If this is not achieved,
      occasional use of alcohol is probably less harmful than daily drinking for
      patients with low or moderate alcohol consumption.

PMID- 12010514
TI  - Chemical synthesis of beta-defensins and LEAP-1/hepcidin.
AB  - A large and steadily growing subfamily of antimicrobially active peptides of
      animals and plants is formed by the defensins, which are highly disulfide-bonded,
      cationic peptides with a molecular mass of about 4 kDa. The synthesis of the
      human beta-defensins 1 and 2 (hBD-1, hBD-2) as well as of the novel murine beta
      defensins 7 and 8 (mBD-7 and mBD-8) is reported. The peptides were synthesized by
      solid-phase peptide synthesis using fluorenylmethoxycarbonyl chemistry. The
      linear products were oxidized in the presence of the cysteine/cystine redox
      system to the biologically active molecules. The correct disulfide connectivity
      of the resulting cyclic products was partly verified by mass spectrometry and
      sequence analysis of the fragments obtained after tryptic cleavage. In addition,
      the recently discovered antimicrobially active human peptide LEAP-1/hepcidin,
      which contains four disulfide bonds, was successfully synthesized and
      subsequently oxidized. For Liver-expressed anti microbial peptide (LEAP)
      1/hepcidin and hBD-1, the identity of native and synthetic peptides was
      demonstrated by high-pressure liquid chromatography and capillary electrophoretic
      analysis. The general synthetic procedure is suitable to rapidly perform the
      total chemical synthesis of novel fully bioactive defensins, which are expected
      to be identified soon, as well as of structurally modified analogs.

PMID- 12010515
TI  - Role of N-t-Boc group in helix initiation in a novel tetrapeptide.
AB  - Protecting groups in N- and C-terminal positions play a decisive role in the
      conformational preference of smaller peptides. Conformational analysis of
      tetrapeptide derivatives containing Ala, Ile and Gly residues was performed.
      Peptide 1, Boc-Ala-Ile-Ile-Gly-OMe (Boc: tert-butyloxycarbonyl) has a
      predominantly helical turn conformation in all the alcoholic solvents studied,
      whereas in the solid state it has a beta-sheet conformation. In contrast, peptide
      2, Ac-Ala-Ile-Ile-Gly-OMe (Ac: acetyl) has a random coil conformation in
      solution. The FTIR spectrum of peptide 1 shows a lower frequency of urethane
      carbonyl, indicating involvement of the carbonyl group in hydrogen bonding in the
      helical turn.

PMID- 12010516
TI  - Isolation and characterization of a novel postsynaptic/cytotoxic neurotoxin from
      Daboia russelli russelli venom.
AB  - A postsynaptic neurotoxin was purified from Daboia russelli russelli venom using
      gel filtration, ion-exchange chromatography and reverse-phase high-performance
      liquid chromatography. The N-terminal sequence, molecular mass and
      pharmacological activities of the neurotoxin/cytotoxin indicate that it is a
      short-chain neurotoxin like that found in Elapid venom. This is the first report
      on the presence of such a postsynaptic neurotoxin from D. r. russelli venom.

PMID- 12010517
TI  - Structure-affinity relationships in the gp41 ELDKWA epitope for the HIV-1
      neutralizing monoclonal antibody 2F5: effects of side-chain and backbone
      modifications and conformational constraints.
AB  - The human monoclonal antibody, mAb 2F5, has broad HIV-1 neutralizing activity and
      binds a conserved linear epitope within the envelope glycoprotein gp41 having a
      core recognition sequence ELDKWA. In this study, the structural requirements of
      this epitope for high-affinity binding to mAb 2F5 were explored using peptide
      synthesis and competitive enzyme-linked immunosorbant assay (ELISA). Expansion of
      the minimal epitope to an end-capped, linear nonapeptide, Ac-LELDKWASL-amide, was
      sufficient to attain maximal affinity within the set of native gp41-sequence
      peptides assayed. Scanning single-residue alanine and d-residue substitutions
      then confirmed the essential recognition requirements of 2F5 for the central DKW
      sequence, and also established the importance of the terminal leucine residues in
      determining high-affinity binding of the linear nonapeptide. Further studies of
      side-chain and backbone-modified analogs revealed a high degree of structural
      specificity for the DK sequence in particular, and delineated the steric
      requirements of the Leu(3) and Trp(6) residues. The nine-residue 2F5 epitope,
      flanked by pairs of serine residues, retained a high affinity for 2F5 when it was
      conformationally constrained as a 15-residue, disulfide-bridged loop. However,
      analogs with smaller or larger loop sizes resulted in lower 2F5 affinities. The
      conformational effects of the gp41 C-peptide helix immediately adjacent to the N
      terminal end of the ELDKWA epitope were examined through the synthesis of helix
      initiated analogs. Circular dichroism (CD) studies indicated that the alpha
      helical conformation was propagated efficiently into the LELDKWASL epitope, but
      without any significant effect on its affinity for 2F5. This study should guide
      the design of a second generation of conformationally constrained ELDKWA analogs
      that might elicit an immune response that mimics the HIV-neutralizing actions of
      2F5.

PMID- 12010518
TI  - Relative hydrophobicity of amino acid residues in homooligopeptides as measured
      by aqueous two-phase partitioning.
AB  - Partitioning of 17 amino acids and their homooligopeptides of different lengths
      in an aqueous dextran-PEG two-phase system containing 0.15 m NaCl in 0.01 M
      sodium phosphate buffer, pH 7.4 and 0.11 m sodium phosphate buffer, pH 7.4 was
      examined. The relative hydrophobicity of the amino acid residues was estimated
      and expressed in equivalent numbers of methylene units. Analysis of the data
      shows that the additivity principle does hold for the hydrophobicity of
      homooligopeptides. The relative hydrophobicity of essentially all amino acid
      residues is noticeably affected by the ionic composition of aqueous media.

PMID- 12010519
TI  - Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine
      containing fMLF analogs.
AB  - In order to explore the properties of chemotactic N-formylpeptides containing
      isopeptide bonds within their backbones, a group of lysine-containing analogs of
      the prototypical chemotactic tripeptide N-formylmethionyl-leucyl-phenylalanine
      (fMLF) was synthesized. The new analogs were designed by adding to the HCO-Met or
      Boc-Met residue a dipeptide fragment made up of Lys and Phe residues joined
      through Lys N alpha or N epsilon bonds, in all possible combinations. Thus, the
      following six pairs of tripeptides were synthesized and examined for their
      bioactivity: RCO-Met-Lys(Z)-Phe-OMe (2a, b), RCO-Met-Lys(Z-Phe)-OMe (3a, b), Z
      Lys(RCO-Met)-Phe-OMe (4a, b), Z-Phe-Lys(RCO-Met)-OMe (5a, b), RCO-Met-Phe-Lys(Z)
      OMe (6a, b) and Z-Lys(RCO-Met-Phe)-OMe (7a, b), with R=OC(CH3)(3 )and R=H for
      compounds a and b, respectively. All the new models were characterized fully and
      their activity (chemotaxis, superoxide anion production and lysozyme release) on
      human neutrophils determined as agonists (compounds b) and antagonists (compounds
      a). All N-formyl derivatives 2b-7b are less potent than fMLF-OMe as
      chemoattractants, but compound 7b exhibits selective activity as superoxide anion
      producer. Derivatives 2a-7a do not show antagonistic activity towards fMLF
      induced chemotaxis and O(2)(-) production, however, all these compounds except 4a
      antagonize lysozyme release by 60%.

PMID- 12010521
TI  - The clinical significance of local chemotherapies.
AB  - This paper discusses differences between statistical and clinical significance.
      It suggests nine factors to consider when assessing clinical significance of
      periodontal therapy. The article reviews the multicentre randomized clinical
      trials on the four antimicrobial local delivery systems commercially available in
      the USA (tetracycline fibre, chlorhexidine chip, doxycycline gel and minocycline
      microspheres) and assesses their data in relation to the nine factors for
      clinical significance. Data from longitudinal studies comparing periodontal
      surgery to non-surgery were evaluated in a similar fashion to provide a frame of
      reference. It was concluded that the local delivery of an antimicrobial offers
      the clinician a statistically and clinically significant option in the treatment
      of chronic periodontitis. It is not an 'either/or' situation in selecting
      therapeutic methods. It is a choice of which treatment method works best for that
      patient by that clinician.

PMID- 12010522
TI  - What is clinical significance?
AB  - This paper summarizes the clinical trial designs for therapies to reverse probing
      depth or control the progression of periodontitis, therapies to be used as an
      adjunct to scaling and root planning, as well as regenerative therapies. The
      approach to statistical significance is summarized and compared to clinical
      significance.

PMID- 12010523
TI  - Clinical significance of non-surgical periodontal therapy: an evidence-based
      perspective of scaling and root planing.
AB  - Analysis of Egyptian hieroglyphics and medical papyri indicate that non-surgical
      periodontal treatment was common 3000-4000 years ago. Even today, scaling and
      root planing (SRP) remains an essential part of successful periodontal therapy.
      The collective evidence from numerous clinical trials reveals a consistency of
      clinical response in the treatment of chronic periodontitis by SRP using manual,
      sonic, or ultrasonic instrumentation. Thus, SRP remains the 'gold standard' to
      which more recently developed therapeutic modalities must be compared. Inherent
      to the clinical evaluation of SRP are such concerns as manual versus sonic and
      ultrasonic instrumentation, control of sub-gingival bacterial populations,
      removal of calculus, root smoothness and changes in various clinical parameters,
      e.g. probing depth, attachment levels, bleeding on probing and gingival
      inflammation. Lastly, an abbreviated discussion is presented on a relatively new
      paradigm of complete mouth 'disinfection' in a compressed time-frame that
      includes SRP as a significant component of the treatment regimen.

PMID- 12010524
TI  - Cross-boundary working--luxury or necessity?

PMID- 12010525
TI  - Studying complex caring interfaces: key issues arising from a study of multi
      agency rehabilitative care for people who have suffered a stroke.
AB  - Ensuring "seamless" health and social services provision has been a concern of
      policy makers for many years but our understanding of this complex system of work
      remains underdeveloped. This article reports selected findings from a series of
      ethnographic case studies of health and social services provision to adults
      recovering from a first acute stroke. Flexible working, the need for a lead
      professional and the transition from hospital to home are themes considered. The
      need for high quality data in order to develop our existing understanding of
      complex caring interfaces is underlined.

PMID- 12010526
TI  - Children's nursing and interprofessional collaboration: challenges and
      opportunities.
AB  - Interprofessional working has been the subject of recent debate in the nursing
      press. Despite this heightened scrutiny little attention has been given to
      putting this development in the context of practitioners working within
      children's nursing. This paper seeks to redress this imbalance by focusing on the
      challenges and opportunities for professional development that interprofessional
      collaboration working offers. This is illustrated by acknowledging existing
      themes of good practice, and identifying the potential for new ways of working
      that maintain professional status, skills and knowledge but also facilitate wider
      collaboration.

PMID- 12010528
TI  - Interprofessional relations: case studies of working relationships between
      Registered Nurses and general practitioners in rural Australia.
AB  - Interprofessional working relationships of nurses and doctors have been discussed
      in the literature but are less frequently the subject of research. A review of
      international research on nurse-doctor professional relationships conducted over
      30 years (1966-99) shows that the relationship is of interest predominantly to
      nurses. From a series of interviews with nurses and doctors, as part of a case
      study of four rural health services, harmonious working relationships between
      nurses and doctors were examined. Further analysis reveals many aspects of nurse
      doctor relationships that are traditional and common across many contexts. There
      are, however, some aspects that are specific to the rural nature of the working
      context and relate well to contemporary advances in nursing knowledge and
      confidence.

PMID- 12010529
TI  - Nursing-led in-patient units for intermediate care: a survey of multidisciplinary
      discharge planning practice.
AB  - The effectiveness of post-acute intermediate care in nursing-led intermediate
      care in-patient units (NLIU) has been studied over the past 20 years. Accounts,
      both positive and negative, have tended to view it as a uni-disciplinary
      intervention. The previous studies are in effect a series of single case studies
      and as such need to be accompanied by richer descriptions of care processes in
      order to be useful. A survey was conducted, in parallel with a randomized
      controlled trial (n=177), to compare multidisciplinary care and discharge
      planning practice on the NLIU with 16 wards that referred patients to it. The
      findings identify that a wide range of professions participate in care on the
      NLIU with physiotherapists and occupational therapists most widely involved. In
      general the team composition and care processes differed little between the NLIU
      and control wards. There was some evidence that there was lower participation in
      care on the NLIU from occupational therapy and social work. It is concluded that
      the NLIU is a complex multidisciplinary intervention. Positive results from some
      NLIUs may only be generalizable to settings with similar skill mix across the
      multidisciplinary team as that found in the acute hospital. Reduced skill mix may
      be a causal factor leading to extended stays and increased total care costs. This
      caution should be extended to other models of intermediate care, whether or not
      they are nursing-led.

PMID- 12010530
TI  - Cross-boundary working: a macro-political analysis of the impact on professional
      roles.
AB  - This paper reviews the policy developments impacting on professional roles and
      boundaries in health and social care. A macro-political analysis is used to offer
      a challenging critique to many of the assumptions associated with cross-boundary
      working. It explores issues such as: whether or not new nursing roles are truly
      being developed to meet need; the myths and realities of interprofessional
      working; how competence can be assured; the need for new forms of professional
      regulation; the implications for professional education of initiatives such as
      national occupational standards and shared learning; planning the future health
      care workforce; and the need for rigorous and robust evaluation of service and
      role developments. Through this exploration the likely consequences of political
      and professional initiatives for both cross-boundary working and the profession
      of nursing itself are illuminated.

PMID- 12010531
TI  - A proposal that patients be considered honorary members of the healthcare team.
AB  - Most research on cross-boundary issues in healthcare focuses on boundaries
      between groups of healthcare professionals, or between different healthcare
      settings. This paper considers the boundary between healthcare professionals and
      their patients, as complementary providers of care to the individual. Following
      major surgery, patients now spend the vast majority of their rehabilitation
      period in their own homes. This raises questions about where to draw the boundary
      around a healthcare intervention, and how to allocate and support responsibility
      for care once the patient is home. This paper reports the findings of a study
      within orthopaedic surgery that followed patients from a few weeks before their
      surgery to 3 months afterwards, recording their interpretations of their
      healthcare experiences. Most patients were keen to take responsibility for
      playing their part in trying to optimize the outcome of their surgery, but many
      were frustrated by lack of information and support to allow them to fulfil this
      role to their satisfaction. Reconceptualization of patients as honorary members
      of the healthcare team may facilitate the development of a framework within which
      the potential contribution of patients to their own care could be valued and
      supported more effectively. This would contribute towards optimizing patient
      outcomes and increasing patient satisfaction with care.

PMID- 12010532
TI  - Health and social care futures in Ireland: the need for cross-boundary work.
AB  - Fundamental changes are taking place in health and social care. The drivers for
      these changes include new discoveries, new treatments and globalization and the
      need to examine and consider cross-boundary work. This paper will outline some of
      the issues generated from a research project that aimed to provide an all-Ireland
      perspective on health and social care futures and to examine the implications of
      these trends both for nursing specifically and health and social care generally.
      Cross-boundary working is important in relation to health and social care
      futures. This incorporates cross-boundary working to include interprofessional,
      intraprofessional and interagency but also cross-border working with the Republic
      of Ireland. There is a great potential for cross-boundary work in nursing as we
      look towards the future. Nonetheless, it needs to be acknowledged that working
      across sectors, departments and even borders is not easy and barriers do exist.
      Some of the implications for nursing include the need to re-examine nursing roles
      and span the boundaries of our profession with the increasing development of
      nurse-led services. In addition nurses need to develop ways of "working together"
      strategically with others to achieve the public health agenda.

PMID- 12010533
TI  - Nursing care and collaborative practice.
AB  - This article argues that the time is right for nurses in the UK to become the
      case managers in all healthcare settings. The re-launch of family health nursing,
      as a model for the organization and delivery of nursing care in the community,
      and the advent of the GP practice-based self-managed integrated nursing teams,
      offer the means by which to take up the opportunities presented by recent
      legislation and the national strategies for promoting partnership working and
      collaborative practice. Nurses could approach this by combining their current
      involvement with developing the single assessment process for older people with
      the overall development of interprofessional collaborative practice across all
      boundaries in health and social services. Despite the new opportunities, this
      will not be straightforward because of the still existing problems associated
      with the health and social care divide. In order to generate high quality care,
      it is imperative for nurses and their patients that the profession gains control
      and ownership of its own policy, remit and practice. Nursing care should be
      defined according to the patient's condition, so that their dependency level,
      diagnostic picture and potential for rehabilitation govern the eligibility
      criteria for health or social care and not the level of technicality in the task
      itself.

PMID- 12010534
TI  - Exploring multi-agency working in services to disabled children with complex
      healthcare needs and their families.
AB  - Children with complex healthcare needs typically require technical and/or medical
      equipment in the home. This growing group of children and families need support
      that crosses agency and professional boundaries, necessitating effective multi
      agency working. There are many examples of multi-agency working around the United
      Kingdom (UK), some specifically designed to meet the needs of children with
      complex healthcare needs and their families. Recent legislation and policy
      statements have highlighted the importance of joint planning and working.
      Currently no research exists that examines the impact of these initiatives on
      disabled children with complex healthcare needs and their families. The "Working
      Together" project is an ongoing research study based at the Norah Fry Research
      Centre, University of Bristol, Bristol, UK. The project aims to explore the
      impact of multi-agency work on children with complex healthcare needs and their
      families. This paper examines the literature on barriers to disabled children and
      the need for multi-agency working. It also considers the concept of multi-agency
      working and how different approaches to working together might be perceived by
      children and families.

PMID- 12010535
TI  - Reflections on a community action research project: interprofessional issues and
      methodological problems.
AB  - This paper describes an action research study in a community setting. A group of
      residents from a local housing estate and a number of local workers used
      participative methods to explore local child care issues with the aim of
      developing initiatives for improved child care. The paper describes the study
      processes and reflects on lessons learnt. A discussion of implications for
      interprofessional working concludes the paper and includes emphasis of the need
      to focus on shared objectives, and develop appropriate organizational structures
      and educational provision.

PMID- 12010536
TI  - Crossing boundaries, re-defining care: the role of the critical care outreach
      team.
AB  - There is clear indication that both government and professional policy in the
      United Kingdom supports a radical change in the role of healthcare practitioners,
      with a move towards a patient-focused service delivered by clinical teams working
      effectively together. Recent health service imperatives driving the agenda for
      flexible clinical teams have occurred simultaneously with an increased public and
      political awareness of deficits in availability of critical care services.
      Against this policy backdrop, working across professional and organizational
      boundaries is fundamental to supporting quality service improvements. In the
      acute care sector, the development of critical care outreach teams is an
      innovation that seeks to challenge the traditional support available for sick
      ward patients. Activity data and observations from the first 6-month evaluation
      of two critical care outreach teams identify the need for clinical support and
      education offered by critical care practitioners to ward-based teams. The
      experiences from such flexible clinical teams provides a foundation from which to
      explore key issues for intradisciplinary and interdisciplinary working across
      clinical areas and organizational boundaries. Adopting innovative approaches to
      care delivery, such as critical care outreach teams, can enable clinical teams
      and NHS trusts to work together to improve the quality of care for acutely ill
      patients, support clinical practitioners working with this client group, and
      develop proactive service planning.

PMID- 12010537
TI  - Communities of practice: an opportunity for interagency working.
AB  - A particular approach to collaborative interagency working is that of
      multiprofessional "communities of practice". Four such groups are described in
      the context of two action research projects, one relating to primary care and the
      other to outpatient services for dermatology and ENT. The facilitating features,
      and the challenges and the potential of working in this way, are discussed, both
      from the point of view of understanding how knowledge is used and valued in such
      groups and as a useful mechanism for the development of services that span
      different professional perspectives and involve consumer interests.

PMID- 12010538
TI  - Cross-boundary working: implications for the multiprofessional team.
AB  - This paper explores cross-boundary working and the impact it may have on the
      manner in which multiprofessional teams function. It draws on data collected for
      a study commissioned by the Department of Health, Human Resource Initiative
      entitled Evaluating New Roles in Practice (ENRiP). A series of case studies
      formed one part of the study that aimed to map the process of implementation of
      new roles in practice, identify the organizational barriers and levers that
      affected the implementation process and explore the meaning of the new roles from
      the perspective of postholders, patients and stakeholders. A naturalistic
      approach to enquiry was taken using a combination of participant observation,
      interviews and reflection. The article includes an overview of the current
      context in which cross-boundary work is developing, a review of current
      literature related to multiprofessional issues and team-working, a brief
      descriptions of the typology of new roles that emerged as one strand of the ENRiP
      study, and the impact that these roles had on both interprofessional and
      multiprofessional working. It concludes with a discussion of the implications for
      practice and the need to ensure that both education and policy are considered in
      planning for the future.

PMID- 12010539
TI  - Teamworking in community rehabilitation.

PMID- 12010540
TI  - Comparison of the sensitivity of manual and automated immunomagnetic separation
      methods for detection of Shiga toxin-producing Escherichia coli O157:H7 in milk.
AB  - AIM: To determine the sensitivity of methods for detection of injured and
      uninjured Escherichia coli O157:H7 (E. coli O157) in raw and pasteurized milk.
      METHODS AND RESULTS: Raw milk, pasteurized milk with 1.5% fat content and
      pasteurized milk with 3.5% fat content were spiked with E. coli O157 at low
      levels. The samples were enriched in modified tryptone soya broth with novobiocin
      (mTSBn) at 37 degrees C. Aliquots of the enriched culture were analysed either by
      manual immunomagnetic separation (MIMS) and culturing on sorbitol MacConkey agar
      with or without cefixime and potassium tellurite (SMACct or SMAC), or by
      automated immunomagnetic separation and integrated ELISA (EiaFosstrade mark).
      Uninjured E. coli O157 organisms were detected in milk by both methods at 1 cfu
      10 ml-1 sample). Injured organisms were detected at levels of about 4 cfu 10 ml-1
      sample. Direct enrichment in mTSBn (22 h incubation) showed better sensitivity
      for injured cells than enrichment in buffered peptone water (BPW, 22 h
      incubation), or in a two-step enrichment consisting of BPW (6 h, 37 degrees C)
      and mTSBn (16 h, 37 degrees C), successively. CONCLUSIONS: The methods showed
      equal sensitivity in that they were both able to detect 1 cfu 10 ml-1 milk
      sample. Injured organisms can be detected and isolated at a level almost as low
      as this. A resuscitation step is not recommended for the detection and isolation
      of injured and non-injured E. coli O157 from milk. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Due to the dilution of contamination in the bulk tank, analysis of milk
      for the presence of E. coli O157 requires a very sensitive method. Both methods
      described here are useful for such analysis.

PMID- 12010541
TI  - Comparison of ATP and in vivo bioluminescence for assessing the efficiency of
      immunomagnetic sorbents for live Escherichia coli O157:H7 cells.
AB  - AIMS: To develop methods to assess the efficiency of immunomagnetic separation
      (IMS). METHODS AND RESULTS: The capturing efficiency of biosorbents for
      Escherichia coli O157:H7, constructed using streptavidin-coated magnetic beads
      and biotinylated antibodies, was tested using both in vivo and ATP
      bioluminescence. Both methods were suitable for the enumeration of bacteria
      captured by the biosorbents. The level of both ATP and in vivo bioluminescence
      depended on the media used, but was unaffected by the magnetic beads. The capture
      efficiency depended on time and sample volume, but did not depend on the length
      of spacer arm of the biotinylation agent. For cell concentrations of <or= 105 cfu
      ml-1, in a 1-ml sample volume, nearly 80-85% recovery of the pathogen was
      observed after 0.5 h of incubation. For an 11-ml sample containing 104 cfu ml-1,
      maximum recovery (50% of cells) was achieved only after 2 h incubation.
      CONCLUSIONS: The detection limit of an ATP-based bioluminescent assay for E. coli
      O157:H7 was reduced by 1 log cycle after optimization of IMS. The bioluminescent
      methods could be used for screening and testing the affinity of antibodies or
      other affinity elements of biosorbents towards live bacterial cells. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Bioluminescent assays provide an easy way to optimize
      conditions for the capture of bacteria by biosorbents in real time.

PMID- 12010542
TI  - D,L-Hydantoinase activity of an Ochrobactrum anthropi strain.
AB  - AIMS: A microorganism with the ability to release methionine from D,L-(2
      methylthioethyl) hydantoin (strain 245) was isolated from soil. The aim of this
      study was the identification of the strain and the adjustment of the conditions
      of growth and of the enzymatic reaction, in order to achieve high specific
      activities of bioconversion of the hydantoin. METHODS AND RESULTS: Strain 245 was
      identified as Ochrobactrum anthropi. The strain grew at alkaline pH (up to 10.0)
      and its hydantoinase activity was found to be inducible by the substrate D,L-(2
      methylthioethyl) hydantoin. The enzyme is also alkalostable, with a pH optimum of
      9.0. Under these conditions, hydantoinase activity was significantly enhanced and
      its half life prolonged when 200 mmol l-1 ammonium and phosphate were added. The
      addition of Ca2+, Na+, Cu2+, Co2+, Mg2+, Zn2+ or Fe3+ (0.5 mmol l-1) to the
      reaction mixture increased the hydantoinase activity of strain 245 up to tenfold
      after 24 h of incubation, compared with unamended controls. CONCLUSION: The
      adequate adjustment of some environmental parameters (pH, addition of inducer,
      presence of ammonium, phosphate, heavy metals and other ions) can considerably
      increase the D, L-hydantoinase activity of strain 245. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The findings reported here set up the initial conditions for a further
      application of strain 245 in the production of methionine from hydantoine.

PMID- 12010544
TI  - Comparison of chickpea rhizobia isolates from diverse Portuguese natural
      populations based on symbiotic effectiveness and DNA fingerprint.
AB  - AIMS: To test the hypothesis that differences in chickpea yields obtained in four
      distinct Portuguese regions (Beja, Elvas-Casas Velhas, Elvas-Estacao Nacional de
      Melhoramento de Plantas (ENMP) and Evora) could be due to variation between the
      natural rhizobia populations. METHODS AND RESULTS: Estimation of the size of the
      different rhizobial populations showed that Elvas-ENMP population was the largest
      one. Elvas-ENMP population also revealed a higher proportion of isolates carrying
      more than one plasmid. Assessment of genetic diversity of the native rhizobia
      populations by a DNA fingerprinting PCR method, here designated as DAPD (Direct
      Amplified Polymorphic DNA), showed a higher degree of variation in Elvas-ENMP and
      Beja populations. The symbiotic effectiveness (SE) of 39 isolates was determined
      and ranged 13-34%. Statistical analysis showed that SE was negatively correlated
      with plasmid number of the isolate. CONCLUSIONS: The largest indigenous rhizobia
      population was found in Elvas-ENMP. DAPD pattern and plasmid profile analysis
      both suggested a higher genetic diversity among the populations of Elvas-ENMP and
      Beja. No relationship was found between SE of the isolates and their origin site.
      SIGNIFICANCE AND IMPACT OF STUDY: The large native population, rather than the
      symbiotic performance of individual rhizobia, could contribute to the higher
      chickpea yields obtained in Elvas-ENMP.

PMID- 12010543
TI  - Plasma membrane injury induced by nonyl gallate in Saccharomyces cerevisiae.
AB  - AIMS: The aim was to investigate the antifungal actions of nonyl gallate against
      Saccharomyces cerevisiae ATCC 7754. METHODS AND RESULTS: The maximum potency of
      both the growth inhibitory and the fungicidal effect against the yeast strain was
      found in nonyl gallate among n-alkyl gallates tested. Nonyl gallate induced ROS
      generation dose-dependently in growing cells. This ester rapidly killed yeast
      cells even when cell division was restricted by cycloheximide. This ester
      inhibited glucose-induced medium acidification and promoted the efflux of
      intracellular potassium ions in a nongrowing condition. Moreover, nonyl gallate
      induced a leakage of calcein from artificially prepared liposomes to a greater
      extent than dodecyl gallate did. CONCLUSIONS: These results suggested nonyl
      gallate injured plasma membrane of S. cerevisiae, resulting in its exhibition of
      fungicidal effect accompanying with a leakage of intracellular materials from the
      cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reveals new knowledge on
      the antifungal actions of nonyl gallate against S. cerevisiae. When nonyl gallate
      is applied as a food preservative, the level of its addition to foods may be
      reduced because of its potent antifungal activity compared with weak acids
      including sorbic acid and benzoic acid.

PMID- 12010545
TI  - Carton sterilization by u.v.-C excimer laser light: recovery of Bacillus subtilis
      spores on vegetable extracts and food simulation matrices.
AB  - AIMS: To determine the recovery of Bacillus subtilis spores loaded onto preformed
      cartons and irradiated with u.v.-excimer laser (248 nm) light. METHODS AND
      RESULTS: Bacillus subtilis spores irradiated with u.v.-excimer laser light
      retained phase brightness, but were blocked at various stages of germination. In
      the presence of germinant, the majority of spores began to lose phase brightness
      but only after an extended lag period (ca 90 min). After 6 h ca 9% of the spores
      had elongated but failed to form new cells, approx. 12% had undergone partial
      phase darkening (grey spores), 15% remained phase bright whilst the remainder had
      turned fully phase dark but failed to elongate. No enhanced recovery of u.v.
      treated spores (with intact or permeabilized coats) occurred in media containing
      hen egg white lysozyme or vegetable extracts (celery, carrot, swede or turnip).
      However, recovery did occur when irradiated spores were incubated for 26 d,
      semiaerobically, within cartons containing nutrient broth or milk. CONCLUSIONS:
      The germination ability of B. subtilis spores is altered following u.v.-excimer
      laser treatment. Recovery of treated spores was found in liquid systems but not
      on agar plates supplemented with vegetable extracts or lysozyme. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The potential recovery of u.v.-excimer laser-treated spores
      in a range of carton-packed food systems requires further investigation.

PMID- 12010546
TI  - Survival and naphthalene-degrading activity of Rhodococcus sp. strain 1BN in soil
      microcosms.
AB  - AIMS: The survival and activity of Rhodococcus sp. strain 1BN, inoculated into
      naphthalene-contaminated sandy-loam soil microcosms, were studied using classical
      and molecular methods. METHODS AND RESULTS: The naphthalene-degrading activity of
      1BN in microcosms was examined through viable counts, CO2 production and
      naphthalene consumption, while its survival after inoculation was monitored by
      detecting the contemporary presence of alkane and naphthalene degradative genes
      and by analysing the 16S rDNA specific restriction profile. The inoculation of
      1BN did not significantly enhance naphthalene degradation in the naphthalene
      contaminated native soil, where 1BN maintained its catabolic activity also when
      in the presence of indigenous microflora. Instead the rate of naphthalene
      degradation by the inoculated 1BN was greater in sterile naphthalene-contaminated
      soil. The level of 1BN was only slightly higher after inoculation regardless of
      whether indigenous naphthalene-degrading bacteria were present or not and 1BN
      remained viable even when the substrate was depleted. CONCLUSIONS: This study
      documents the colonization and growth of 1BN in a non-sterile, naphthalene-added,
      sandy-loam soil having an active indigenous naphthalene-degrading population.
      SIGNIFICANCE AND IMPACT OF THE STUDY: An active and well-established naphthalene
      degrading bacterial population in the native soil did not hamper the survival of
      the introduced 1BN that, through its activity, enhanced the mineralization rate
      of naphthalene.

PMID- 12010547
TI  - An investigation into the changed physiological state of Vibrio bacteria as a
      survival mechanism in response to cold temperatures and studies on their
      sensitivity to heating and freezing.
AB  - AIMS: To induce pathogenic Vibrio bacteria into a changed physiological state, in
      response to cold temperatures in sea water, and assess their sensitivity to
      heating and freezing, as compared with normal cells. METHODS AND RESULTS: Cells
      of exponential phase Vibrio vulnificus, V. cholerae and V. parahaemolyticus were
      washed and inoculated into flasks of sea water, which were stored at 20 and 4
      degrees C. Cells stored at 20 degrees C could be recovered after 60 d on non
      selective agar (heart infusion agar; HIA) and on the selective agar (thiosulphate
      citrate bile salts agar) which is used in most Vibrio detection methodology. At 4
      degrees C cells became non-culturable on both agars over time. The non-culturable
      cells appeared to be metabolically active and maintained their membrane
      integrity, whilst undergoing a change in morphology from rod-shaped to coccoid
      cells. Resuscitation was possible, in some cases, by an upshift in temperature
      before plating and the addition of catalase to HIA plates was found to increase
      recovery. Studies were carried out to assess the sensitivity of the non
      culturable cells to heating and freezing compared with the normal cells. Vibrio
      organisms, whether culturable or in the non-culturable form, were not inactivated
      by freezing to -20 degrees C. Heating studies showed that V. parahaemolyticus was
      very heat resistant at low temperatures. However, a pasteurization regime of 2
      min at 70 degrees C was found to be effective against all three strains.
      Experiments showed that the non-culturable cells of all three strains were
      similar in their heat resistance or, in some cases, were more heat sensitive than
      cells in the normal form. CONCLUSIONS: Cells in the changed physiological form
      would not be detected in fish or seafood products by the current Vibrio detection
      methods. Freezing had no effect in reducing cell numbers. Vibrio parahaemolyticus
      was very heat resistant in the low temperature pasteurization studies. The higher
      pasteurization regime of 70 degrees C for 2 min was effective against all three
      pathogens. Non-culturable cells had similar heat sensitivity or were more heat
      sensitive than cells in the normal state. SIGNIFICANCE OF IMPACT OF THE STUDY:
      The study has highlighted a need for the development of better Vibrio detection
      methods. The low temperature pasteurization of oysters, which has been
      recommended in the USA, would not be adequate against the strain of V.
      parahaemolyticus used in this study. Heating regimes which were found to control
      cells in the normal form will also be effective for the control of the cells with
      changed physiology.

PMID- 12010548
TI  - Biological control of cucumber and sugar beet damping-off caused by Pythium
      ultimum with bacterial and fungal antagonists.
AB  - AIMS: Five bacterial strains belonging to Bacillus subtilis, Pseudomonas
      fluorescens and Ps. corrugata and two fungal strains belonging to Trichoderma
      viride and Gliocladium virens were evaluated for their efficacy in controlling
      sugar beet and cucumber damping-off caused by Pythium ultimum. METHODS AND
      RESULTS: The in vitro antagonistic activity of bacteria against various Pythium
      spp. was evaluated with dual cultures in various media. Pseudomonas strains
      inhibited the pathogen better than Bacillus strains. To identify potentially
      useful antagonist combinations, dual compatibility of antagonists was also
      evaluated, based on growth in two liquid media containing substrate previously
      used by other antagonists. Four pairs of bacteria were selected. Sugar beet
      damping-off biocontrol was attempted with bacterial seed treatments (individually
      and in pairs). Cucumber damping-off biocontrol was attempted with bacterial seed
      treatments and bacterial and fungal compost treatments. In sugar beet,
      satisfactory biocontrol was only achieved with Pseudomonas antagonists.
      Antagonist combinations did not show any superior biocontrol ability to
      individual antagonists and compatibility of bacteria in vitro did not correlate
      with compatibility in vivo. Bacterial seed treatments and fungal compost
      treatments failed to control cucumber damping-off. Better biocontrol in cucumber
      was achieved when bacterial antagonists were applied by drenching or by coating
      seed with bacteria in a peat carrier. CONCLUSIONS: Pseudomonas antagonists were
      superior to Bacillus antagonists in controlling damping-off in cucumber and sugar
      beet. Pseudomonas peat inocula maintained a good shelf-life 2 years after
      preparation. SIGNIFICANCE AND IMPACT OF THE STUDY: Pseudomonas peat formulations
      have the potential for development into commercial biopesticides.

PMID- 12010549
TI  - Relevance of incubation temperature for Vibrio salmonicida vaccine production.
AB  - AIMS: To investigate the relationships between water temperature, bacterial
      growth, virulence and antigen expression in Vibrio salmonicida, the causal agent
      of cold water vibriosis in Atlantic salmon (Salmo salar L.). METHODS AND RESULTS:
      The significance of sea temperature was investigated using historical clinical
      and oceanographic data. An upper threshold for disease of approx. 10 degrees C
      was established. The effects of culture temperature and media type on bacterial
      growth were studied on solid and in liquid media. The highest rates of cell
      division were identified at 15 degrees C on solid media and 10 degrees C in
      liquid media. Outer membrane protein (OMP) expression and serological response in
      Atlantic salmon were studied using sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis, Western blotting and enzyme-linked immunosorbent assay. A novel
      76-kDa OMP produced in unshaken cultures at 10 degrees C was not found to
      stimulate a specific humoral response. CONCLUSIONS: Diagnostic agar plate-based
      incubation of suspected V. salmonicida should be carried out at 15 degrees C.
      High yield broth cultures for vaccine production should be incubated at 10
      degrees C or lower. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is, to the
      best of our knowledge, the first to identify different optimal temperatures in a
      bacterial species cultured on physically different types of media. The evidence
      presented suggests that V. salmonicida and possibly other bacteria destined for
      vaccine use in poikilothermic organisms should be cultured at temperatures
      consistent with that at which disease occurs.

PMID- 12010550
TI  - The effect of toluidine blue on the survival, dormancy and outer membrane porin
      proteins (OmpC and OmpF) of Salmonella typhimurium LT2 in seawater.
AB  - AIMS: To study the relationship between changes in the composition of the outer
      membrane proteins and the survival of Salmonella typhimurium LT2 in filtered
      autoclaved seawater containing Toluidine Blue (TB) dye as a photosensitizer.
      METHODS AND RESULTS: In samples exposed to TB and excited by artificial visible
      light, the total viable (TVC) and respiring cell counts (RCC) showed that,
      although the TVC declined to an undetectable level in 6.5 h, the RCC showed that
      some cells were still capable of respiration. The porin protein composition
      changed gradually with OmpC and OmpF becoming undetectable by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis after 8 h of incubation. Hydrogen
      peroxide-pretreated cells survived longer compared with the control. CONCLUSIONS:
      Oxidative pretreatment of Salm. typhimurium protects cells from some of the
      effects of sunlight in the presence of photosensitizers. The changes in porin
      proteins may play a role in this protection. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study shows that the survival of bacteria under conditions of stress
      is the result of a linked series of reactions.

PMID- 12010551
TI  - Analysis of the properties of spores of Bacillus subtilis prepared at different
      temperatures.
AB  - AIMS: To determine the effect of sporulation temperature on Bacillus subtilis
      spore resistance and spore composition. METHODS AND RESULTS: Bacillus subtilis
      spores prepared at temperatures from 22 to 48 degrees C had identical amounts of
      dipicolinic acid and small, acid-soluble proteins but the core water content was
      lower in spores prepared at higher temperatures. As expected from this latter
      finding, spores prepared at higher temperatures were more resistant to wet heat
      than were spores prepared at lower temperatures. Spores prepared at higher
      temperatures were also more resistant to hydrogen peroxide, Betadine,
      formaldehyde, glutaraldehyde and a superoxidized water, Sterilox. However, spores
      prepared at high and low temperatures exhibited nearly identical resistance to
      u.v. radiation and dry heat. The cortex peptidoglycan in spores prepared at
      different temperatures showed very little difference in structure with only a
      small, albeit significant, increase in the percentage of muramic acid with a
      crosslink in spores prepared at higher temperatures. In contrast, there were
      readily detectable differences in the levels of coat proteins in spores prepared
      at different temperatures and the levels of at least one coat protein, CotA, fell
      significantly as the sporulation temperature increased. However, this latter
      change was not due to a reduction in cotA gene expression at higher temperatures.
      CONCLUSIONS: The temperature of sporulation affects a number of spore properties,
      including resistance to many different stress factors, and also results in
      significant alterations in the spore coat and cortex composition. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The precise conditions for the formation of B. subtilis
      spores have a large effect on many spore properties.

PMID- 12010552
TI  - Novel intercellular communication system in Escherichia coli that confers
      antibiotic resistance between physically separated populations.
AB  - AIMS: To determine whether intercellular signalling can occur between physically
      separated populations of Escherichia coli. METHODS AND RESULTS: Intercellular
      signalling between physically discrete populations of E. coli BL21 was analysed
      in bi-partite Petri dishes. Transfer of a growth-promoting signal resulted in
      induction of resistance to the antibiotic ampicillin. Optimal expression of the
      signal occurred when the signalling population was established as a bacterial
      lawn for 24 h. This represented an entry into the stationary phase of growth, as
      indicated by the expression profile of the RNA polymerase subunit sigma38
      (sigmaS; sigma S). The growth-promoting effect was also observed when E. coli
      DH5alpha (luxS-) was used as the signalling population. Preventing passage of air
      between the two populations resulted in a complete cessation of the growth
      promoting effect. CONCLUSIONS: A growth-promoting signal occurs between
      physically separated cultures of E. coli. The exact nature of the signal remains
      to be determined but does not involve the production of autoinducer-2 from the
      luxS gene. Signal transmission is likely to involve airborne transfer of a signal
      species. SIGNIFICANCE AND IMPACT OF THE STUDY: Intercellular signalling systems
      exist in bacteria that enable antibiotic resistance to be conferred between
      physically separated populations.

PMID- 12010553
TI  - Occurrence of pathogenic vibrios in coastal areas of France.
AB  - AIMS: This study was carried out to investigate the occurrence of potentially
      pathogenic species of Vibrio in French marine and estuarine environments. METHODS
      AND RESULTS: Samples of coastal waters and mussels collected between July and
      September 1999 were analysed by culture, using selective media including
      thiosulphate-citrate-bile salts-sucrose and modified cellobiose-polymixin B
      colistin agar. Presumptive Vibrio colonies were isolated and identified using
      selected biochemical tests. Specific primers based on flanking sequences of the
      cytolysin, vvhA gene, pR72H DNA fragment and 16S-23S rRNA intergenic spacer
      region (ISR) were used in a polymerase chain reaction (PCR) to confirm the
      identification of Vibrio vulnificus, V. parahaemolyticus and V. cholerae,
      respectively. In this study, V. alginolyticus (99 of 189) was the predominant
      species, followed by V. parahaemolyticus (41 of 189), V. vulnificus (20 of 189)
      and non-O1/non-O139 V. cholerae (three of 189). All 20 V. vulnificus isolates
      showed PCR amplification of the vvhA gene, 16 of which had been isolated from
      estuarine water. The PCR amplification of the pR72H DNA fragment in 41 V.
      parahaemolyticus isolates generated two unique amplicons of 387 and 320 bp. The
      latter, present in 24.4% of these isolates, had not previously been found in V.
      parahaemolyticus strains examined to date. Amplification of the trh gene in two
      of the isolates suggested these to be virulent strains. Three strains identified
      as V. cholerae by amplification of the 16S-23S rRNA ISR were confirmed to be non
      cholera (non-O1/non-O139) strains. CONCLUSIONS: The results of this study
      demonstrated the presence of pathogenic Vibrio species in French coastal waters.
      Furthermore, the PCR approach proved useful for the rapid and reliable
      confirmation of species identification. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These findings indicate the potential sanitary risk associated with the presence
      of pathogenic Vibrio spp. in cultivated mussels and in the aquatic environment.
      The PCR can be used to detect pathogenic vibrios directly in environmental
      samples.

PMID- 12010554
TI  - Purification and properties of a histidine decarboxylase from Tetragenococcus
      muriaticus, a halophilic lactic acid bacterium.
AB  - AIMS: A histidine decarboxylase from Tetragenococcus muriaticus, a halophilic
      histamine-producing bacterium isolated from Japanese fermented squid liver sauce,
      was purified to homogeneity, for the first time. METHODS AND RESULTS: The enzyme
      was purified 16-fold from cell-free extract by ammonium sulphate precipitation,
      anion exchange chromatography and hydroxyapatite chromatography. The pure enzyme
      consisted of two polypeptide chains with molecular mass of 28.8 and 13.4 kDa. The
      N-terminal amino acid sequences of these polypeptides highly correlated with
      those of the alpha- and beta-chains of other Gram-positive bacterial histidine
      decarboxylases. The optimum and stable pH for the enzyme was 4.5-7.0 and 4.0-7.0,
      respectively. This enzyme did not decarboxylate lysine, arginine, tyrosine,
      tryptophan and ornithine. The enzyme activity decreased with the addition of
      NaCl. At pH 4.8, the Vmax and Km values were 16.8 micromol histamine min-1 mg-1
      and 0.74 mmol l-1, respectively. CONCLUSIONS: The very similar physiological
      properties of this enzyme and almost identical N-terminal amino acid sequences to
      those from other Gram-positive bacteria indicated that this enzyme may be
      evolutionally highly conserved among Gram-positive bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Information on this enzyme could be useful for studying the
      mechanism of histamine accumulation in salted foods. In addition, the N-terminal
      amino acid sequence can be utilized to design oligonucleotide probes, which may
      prove valuable in the rapid monitoring of halophilic histamine producers in
      salted products.

PMID- 12010555
TI  - Strategies for evaluating the sanitary quality of composting.
AB  - AIMS: To evaluate different strategies for description of the sanitary quality of
      industrial-scale composting. METHODS AND RESULTS: The investigation included
      microbiological analyses of waste at different stages during the process (spot
      test analysis), as well as physical and chemical parameters. The elimination of
      indicator organisms was also investigated by means of direct process evaluation,
      based on inoculation of the waste. At the four investigated facilities, the
      sanitary process was very efficient when evaluated by the direct process
      evaluation, indicated by an efficient elimination of Escherichia coli and
      Enterococcus faecalis inoculated into the waste. The sanitization was poor when
      evaluated by spot test analysis at the two windrow facilities, while good
      agreement was found at the two in-vessel facilities. CONCLUSIONS: The direct
      process evaluation is a valuable tool for identifying parameters for process
      optimization in different zones and for measuring elimination patterns of
      pathogens not normally present in the waste, but it is unreliable for evaluating
      the overall sanitary process. SIGNIFICANCE AND IMPACT OF THE STUDY: The spot test
      analysis is an accurate method for the analysis of the sanitary process. In
      addition, it is simple and inexpensive to perform, which makes it very cost
      effective for supervision of the sanitary quality of industrial-scale composting.

PMID- 12010556
TI  - Recombinant Lactococcus starters as a potential source of additional peptidolytic
      activity in cheese ripening.
AB  - AIMS: The aim of this study was to modulate the lactococcal proteolytic system
      for enhancement of the cheese ripening process. METHODS AND RESULTS: The genes
      encoding PepN, PepC, PepX and PepI peptidases of a highly proteolytic
      Lactobacillus helveticus strain were transferred into Lactococcus lactis in a
      food-grade cloning system. A comparison of the relative peptidase activities from
      the transformants with those from the untransformed host, determined in the
      conditions of maturing cheese, showed that an increase in peptidase activity
      could be achieved by introducing a selected peptidase gene from Lact. helveticus
      into L. lactis. CONCLUSIONS: Recombinant L. lactis starter strains, carrying a
      peptidase gene from Lact. helveticus, may have an important contribution to the
      proteolysis of maturing cheese by producing an additional peptidolytic enzyme
      activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The results will be of importance
      in shortening the ripening period and production of special cheeses (e.g. reduced
      fat cheeses) with improved characteristics.

PMID- 12010557
TI  - Genetic diversity of Salmonella enterica serovar Paratyphi A from different
      geographical regions in Asia.
AB  - AIMS: Subtyping of Salmonella Paratyphi A isolates from India, Pakistan,
      Indonesia and Malaysia was carried out by pulsed-field gel electrophoresis (PFGE)
      to assess the extent of genetic diversity of these isolates from different
      endemic countries. METHODS AND RESULTS: A total of 39 human isolates of
      Salmonella Paratyphi A from Pakistan, India, Indonesia and Malaysia were studied
      using PFGE analysis following digestion of chromosomal DNA with XbaI. Seven
      isolates from Pakistan were resistant to ampicillin, tetracycline and
      cotrimoxazole. It was noted that Salmonella Paratyphi A isolates obtained from
      outbreaks in India had limited genetic diversity and probably belonged to closely
      related clones. Significant genetic homogeneity was observed among antimicrobial
      resistant isolates from Pakistan and antimicrobial-sensitive isolates from
      Pakistan and Indonesia, respectively. CONCLUSIONS: PFGE was a useful subtyping
      technique to differentiate Salmonella Paratyphi A from different endemic
      countries. However, it fails to differentiate the antimicrobial-resistant and 
      sensitive strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of the
      present study verify the usefulness of PFGE in characterizing and comparing
      strains of Salmonella Paratyphi A. Our study suggests that a limited number of
      clones are responsible for paratyphoid fever in these countries.

PMID- 12010558
TI  - Occurrence of Staphylococcus and enteropathogens in soft cheese commercialized in
      the city of Rio de Janeiro, Brazil.
AB  - AIMS: To investigate the presence of Staphylococcus aureus, enteropathogenic
      Escherichia coli (EPEC), Aeromonas spp. and Yersinia spp. in soft cheese
      commercialized in Rio de Janeiro, Brazil. METHODS AND RESULTS: A total of 45
      samples of cheese from three different brands marketed in Rio de Janeiro city
      were analysed for faecal coliform levels using the Most Probable Number (MPN)
      technique. The samples were also analysed using conventional methodology for the
      investigation of food-borne pathogens. High levels of faecal contamination were
      detected in 95.5% of cheese samples. Staphylococcus aureus was isolated from 20%
      of samples, of which 17.7% were above the limits allowed by Brazilian
      legislation. Aeromonas hydrophila and Aer. caviae were detected in 17.7% of the
      samples. Yersinia spp. were not found in this study. EPEC was isolated from 21.1%
      of the samples and the most frequently found serogroups were O127, followed by
      O55 and O26. CONCLUSIONS: Our results showed that 95.5% of cheese samples had
      high levels of faecal coliforms. The isolation of Staph. aureus, serogroups of
      EPEC and Aeromonas spp. suggested that the soft cheese commercialized in the city
      of Rio de Janeiro may represent a health risk for the consumers. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These results suggest that soft cheese may act as an
      important vehicle of transmission for well-established pathogens.

PMID- 12010559
TI  - International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 7th
      Annual International Meeting. May 19-22, 2002. Arlington, Virginia, USA.
      Abstracts.

PMID- 12010562
TI  - Glucocorticoids: do we know how they work?
AB  - It is not known to what extent glucocorticoid hormones cause their anti
      inflammatory actions and their undesirable side effects by the same or different
      molecular mechanisms. Glucocorticoids combine with a cytoplasmic receptor that
      alters gene expression in two ways. One way is dependent on the receptor's
      binding directly to DNA and acting (positively or negatively) as a transcription
      factor. The other is dependent on its binding to and interfering with other
      transcription factors. Both mechanisms could underlie suppression of
      inflammation. The liganded receptor binds and inhibits the inflammatory
      transcription factors activator protein-1 and NF-kappaB. It also directly induces
      anti-inflammatory genes such as that encoding the protein inhibitor of NF-kappaB.
      Recent work has shown that glucocorticoids inhibit signalling in the mitogen
      activated protein kinase pathways that mediate the expression of inflammatory
      genes. This inhibition is dependent on de novo gene expression. It is important
      to establish the significance of these different mechanisms for the various
      physiological effects of glucocorticoids, because it may be possible to produce
      steroid-related drugs that selectively target the inflammatory process.

PMID- 12010563
TI  - Statins as modulators of bone formation.
AB  - The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
      to reduce serum cholesterol is well described. However, the recent finding that
      statins have direct effects on bone was unexpected. A number of epidemiological
      studies have recently been published that explore the effects of statins on bone
      mineral density and risk of fracture in humans. Statins may act by directly
      stimulating the expression of bone morphogenetic protein-2 and increasing
      osteoblast differentiation or, like nitrogen-containing bisphosphonates, may have
      effects on the mevalonate pathway that leads to inhibition of osteoclast activity
      and osteoblast apoptosis. In addition, the demonstration that statins can inhibit
      inflammation and encourage angiogenesis offers other possibilities for action.

PMID- 12010564
TI  - Joint disease caused by defective gp130-mediated STAT signaling.
AB  - IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it
      regulates immune responses, acute-phase reactions, and inflammation. IL-6
      signaling is mediated exclusively by the common signal-transducing component
      gp130, which is also essential for signal transduction of other cytokines of the
      leukemia inhibitory factor (LIF)/IL-6 family. M Ernst and colleagues generated
      and studied knock-in mice (gp130DeltaSTAT/DeltaSTAT), in which all STAT-binding
      sites (sites binding signal transducers and activators of transcription) were
      deleted from their gene encoding gp130 but binding sites for both Janus kinases
      (JAKs) and for the protein tyrosine phosphatase-2 (SHP-2) were preserved. They
      found that this mutant mouse displayed a blastocyst implantation defect,
      gastrointestinal ulceration, and, interestingly, severe joint disease with
      representative features of rheumatoid arthritis. Synovial cells from this mouse
      exhibited mitogenic hyper-responsiveness to cytokines of the LIF/IL-6 family, a
      phenomenon that was caused by sustained gp130-mediated SHP-2/Ras/Erk activation
      due to a defect in the induction of SOCS-1 (suppressor of cytokine signaling-1;
      also known as SSI or JAB). This suppressor, induced by STAT signaling, regulates
      cytokine signaling. It is, therefore, conceivable that the disturbance of the
      balanced activation between the STAT and SHP-2/Ras/Erk signal pathways causes the
      joint disease in the gp130DeltaSTAT/DeltaSTAT mouse. These findings may be
      beneficial in the elucidation of the cause and the treatment of rheumatoid
      arthritis in humans.

PMID- 12010565
TI  - Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis:
      integration of complex signaling pathways for the recruitment of gene-specific
      transcription factors.
AB  - Matrix metalloproteinase (MMP)-1, MMP-8 and MMP-13 are interstitial collagenases
      that degrade type II collagen in cartilage; this is a committed step in the
      progression of rheumatoid arthritis and osteoarthritis. Of these enzymes, the
      expression of MMP-1 and MMP-13 is substantially increased in response to IL-1 and
      tumor necrosis factor-alpha, and elevated levels of these collagenases are
      observed in arthritic tissues. Therefore, cytokine-mediated MMP-1 and MMP-13 gene
      regulation is an important issue in arthritis research. In this review, we
      discuss current models of MMP-1 and MMP-13 transcriptional regulation, with a
      focus on signaling intermediates and transcription factors that may be future
      targets for the development of new arthritis drugs.

PMID- 12010566
TI  - Genetic epidemiology: systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised
      phenotypically by fibrosis and ischaemic atrophy. Its aetiology is most likely
      multifactorial. A genetic predisposition to the condition is suggested by reports
      of familial SSc (a positive family history is the strongest risk factor yet
      identified), by animal models, and by disease-association studies, in which
      researchers have examined a wide variety of genes including those involved in
      fibrosis, in vascular function and structure, and in autoimmunity - the relative
      rarity of SSc has precluded linkage studies, except in the Choctaw Indians.
      Recent advances in genetic methodologies should further our understanding of this
      complex disease process.

PMID- 12010567
TI  - T-cell activation without proliferation in juvenile idiopathic arthritis.
AB  - A study was done to determine if the differentiation and activation phenotype of
      T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis
      (JIA) is associated with T-cell proliferation in situ. Mononuclear cells were
      isolated from 44 paired samples of peripheral blood and SF. Differentiation and
      activation markers were determined on CD4 and CD8 T cells by flow cytometry. Cell
      cycle analysis was performed by propidium iodide staining, and surface-marker
      expression was also assessed after culture of the T cells under conditions
      similar to those found in the synovial compartment. The majority of the T cells
      in the SF were CD45RO+CD45RBdull. There was greater expression of the activation
      markers CD69, HLA-DR, CD25 and CD71 on T cells from SF than on those from
      peripheral blood. Actively dividing cells accounted for less than 1% of the total
      T-cell population in SF. The presence or absence of IL-16 in T-cell cultures with
      SF or in a hypoxic environment did not affect the expression of markers of T-cell
      activation. T cells from the SF of patients with JIA were highly differentiated
      and expressed early and late markers of activation with little evidence of in
      situ proliferation. This observation refines and extends previous reports of the
      SF T-cell phenotype in JIA and may have important implications for our
      understanding of chronic inflammation.

PMID- 12010568
TI  - Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant
      arthritis is paralleled by differential influence on NF-kappaB binding activity
      and TNF-alpha secretion of T cells.
AB  - The aim of this study was to analyze the differential effects of three anti-CD4
      monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment
      of rat adjuvant arthritis (AA) and on T-cell function and signal transduction.
      Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs
      W3/25, OX35, and RIB5/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction,
      on the day of induction [day 0], and thereafter). The effects on T-cell
      reactivity in vivo (delayed-type hypersensitivity), ex vivo (ConA-induced
      proliferation), and in vitro (mixed lymphocyte culture) were assessed. The in
      vitro effects of anti-CD4 preincubation on T-cell receptor (TCR)/CD3-induced
      cytokine production and signal transduction were also analyzed. While preventive
      treatment with OX35 and W3/25 significantly ameliorated AA from the onset,
      treatment with RIB5/2 even accelerated the onset of AA by approximately 2 days
      (day 10), and ameliorated the arthritis only in the late phase (day 27).
      Differential clinical effects at the onset of AA were paralleled by a
      differential influence of the mAbs on T-cell functions, i.e. in comparison with
      OX35 and W3/25, the 'accelerating' mAb RIB5/2 failed to increase the delayed-type
      hypersentivity (DTH) to Mycobacterium tuberculosis, increased the in vitro tumor
      necrosis factor (TNF)-alpha secretion, and more strongly induced NF-kappaB
      binding activity after anti-CD4 preincubation and subsequent TCR/CD3-stimulation.
      Depending on their epitope specificity, different anti-CD4 mAbs differentially
      influence individual proinflammatory functions of T cells. This fine regulation
      may explain the differential efficacy in the treatment of AA and may contribute
      to the understanding of such treatments in other immunopathologies.

PMID- 12010569
TI  - Tissue factor as a proinflammatory agent.
AB  - Tissue factor (TF) is a transmembrane glycoprotein and the main triggering
      element of blood coagulation. TF expression on monocytes and endothelial cells is
      induced by exposure to endotoxin, tumor necrosis factor, and IL-1 and is
      considered to appear in consequence of inflammation. In order to assess the
      proinflammatory capacity of TF itself, the recombinant extracellular domain of TF
      was injected intra-articularly into healthy mice. To characterize the role of
      immune cells in the TF-induced arthritis, mice deprived of lymphocytes,
      neutrophils and monocytes were used. Histomorphological analysis of the joints
      with respect to inflammatory cell infiltration, pannus formation and erosion
      formation revealed development of arthritis in 80% of animals injected with TF.
      In most of the cases synovial proliferation was accompanied by pannus formation
      and cartilage destruction. Inflammatory cell infiltrate consisted of CD4-Mac1+
      macrophages. Depletion of monocytes was, however, not enough to abolish
      inflammation. Indeed, combined deficiency of monocytes and lymphocytes was
      required to prevent inflammation following the injection of TF. We observed that
      TF induced chemokine production (MIP-1alpha and RANTES), but did not induce a
      proliferative response nor cytokine release by mouse spleen cells. TF has strong
      inflammatogenic properties mediated predominantly by monocytes and their release
      of chemokines. Our study shows that TF can simultaneously trigger the immune and
      coagulation systems.

PMID- 12010570
TI  - Combined antibiotic and free radical trap treatment is effective at combating
      Staphylococcus-aureus-induced septic arthritis.
AB  - Although early antibiotic treatment of patients with septic arthritis eradicates
      bacteria, joint destruction commonly results from the unregulated host
      inflammatory responses to infection. The spin trap compound phenyl-N-tert-butyl
      nitrone (PBN) has been shown to have both anti-inflammatory and antioxidant
      effects. The aim of this study was to assess the effect of combined systemic
      administration of PBN and cloxacillin on the development of Staphylococcus aureus
      arthritis.Three days after Naval Medical Research Institute (NMRI) mice were
      infected intravenously with S. aureus LS-1, daily treatment was started with
      cloxacillin alone, PBN alone, or cloxacillin and PBN. Arthritis, weight loss and
      general condition were evaluated for each mouse, and joints were analyzed
      histopathologically. Systemic administration of PBN in conjunction with
      cloxacillin ameliorated the course of experimental S. aureus arthritis, as
      evidenced by an increased cure rate. Thus, combinatorial antioxidant plus
      antibiotic anti-inflammatory therapies represent a potentially efficacious
      approach to the management of septic arthritis.

PMID- 12010571
TI  - Differential expression of the angiogenic Tie receptor family in arthritic and
      normal synovial tissue.
AB  - Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that
      play important roles principally during the later stages of angiogenesis. We have
      compared the distribution of the receptor tyrosine kinase (Tie) and the Ang
      ligands in synovial tissues from normal subjects and those with rheumatoid
      arthritis (RA) and osteoarthritis (OA). Immunohistochemical analysis was used to
      determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of
      normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and
      protein expression were quantified in synovial tissues and RA synovial tissue
      fibroblasts with real-time reverse transcription polymerase chain reaction and
      western blot analysis. In RA, Ang-1 positive immunostaining on lining cells,
      macrophages and endothelial cells was significantly higher than in OA and normal
      synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar
      in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial
      tissue from subjects with RA and OA showed a significant upregulation of Tie1 on
      lining cells, macrophages and endothelial cells compared to that from normal
      subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue
      lining cells, macrophages and smooth muscle cells compared to normal synovial
      tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA
      synovial tissue compared to normal and OA synovial tissues, and RA synovial
      tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2
      protein expression in RA and OA synovial tissue compared to RA synovial tissue
      fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression
      over Ang-2 is in agreement with an active neovascularization in RA synovial
      tissue.

PMID- 12010572
TI  - Differential binding of chemokines to macrophages and neutrophils in the human
      inflamed synovium.
AB  - In chronic inflammatory foci, such as the rheumatoid joint, there is enhanced
      recruitment of phagocytes from the blood into the tissues. Chemokines are
      strongly implicated in directing the migration of these cells, although little is
      known regarding the chemokine receptors that could mediate their chemotaxis into
      the joint tissue. Therefore the objective of the study was to identify chemokine
      binding sites on macrophages and neutrophils within the rheumatoid synovium using
      radiolabeled ligand binding and in situ autoradiography. Specific binding sites
      for CCL3 (macrophage inflammatory protein-1alpha), CCL5 (RANTES), CCL2 (monocyte
      chemoattractant protein-1) and CXCL8 (IL-8) were demonstrated on CD68+
      macrophages in the subintimal and intimal layers. The number and percentage of
      intimal cells that bound chemokines were greater in inflamed regions compared to
      noninflamed regions. The intensity of intimal binding varied between chemokines
      with the rank order, CCL3 > CCL5 > CCL2 > CXCL8. Neutrophils throughout the
      synovium bound CXCL8 but did not show any signal for binding CCL2, CCL3 or CCL5.
      Immunohistochemistry showed that both CXCR1 and CXCR2 are expressed by
      macrophages and neutrophils in the rheumatoid and nonrheumatoid synovia,
      suggesting that both of these receptors are responsible for the CXCL8 binding.
      The chemokine binding sites described on phagocytes may be involved in the
      migration of these cells into the inflamed joint.

PMID- 12010573
TI  - Highly efficient genetic transduction of primary human synoviocytes with
      concentrated retroviral supernatant.
AB  - We are developing retroviral-mediated gene transfer to human fibroblast-like
      synovial cells (FLS) as one approach to characterizing genetic pathways involved
      in synoviocyte pathophysiology. Prior work has suggested that FLS are relatively
      refractory to infection by Moloney murine leukemia virus based vectors. To
      determine if viral titer influenced the transduction efficiency of FLS, we
      optimized a rapid, efficient, and inexpensive centrifugation method to
      concentrate recombinant retroviral supernatant. The technique was evaluated by
      measurement of the expression of a viral enhanced green fluorescent protein
      transgene in transduced cells, and by analysis of viral RNA in retroviral
      supernatant. Concentration (100-fold) was achieved by centrifugation of viral
      supernatant for four hours, with 100% recovery of viral particles. The
      transduction of FLS increased from approximately 15% with unconcentrated
      supernatant, to nearly 50% using concentrated supernatant. This protocol will be
      useful for investigators with applications that require efficient, stable, high
      level transgene expression in primary FLS.

PMID- 12010574
TI  - Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung
      tissue of patients with Wegener's granulomatosis.
AB  - Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules
      of human polymorphonuclear leukocytes and serves as the major target antigen of
      antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c
      ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe
      vasculitis in different organs (e.g. kidney, nose and lung). Little is known
      about the expression and distribution of PR-3 in the lung. We found that PR-3 is
      expressed in normal lung tissue and is upregulated in lung tissue of patients
      with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and
      macrophages, and not the neutrophils, express PR-3 most strongly and may
      contribute to lung damage in patients with WG via direct interaction with
      antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR
      3 expression in parenchymal cells of lung tissue could be at least one missing
      link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.

PMID- 12010575
TI  - Production of interleukin-1 receptor antagonist by human articular chondrocytes.
AB  - Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing
      anti-inflammatory properties. IL-1Ra is produced as different isoforms, one
      secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3),
      derived from the same gene. We examined the production of IL-1Ra species by
      cultured human articular chondrocytes in response to various cytokines. The
      levels of IL-1Ra were undetectable in culture supernatants of untreated cells,
      but were significantly increased by IL-1beta. Cell lysates contained very low
      levels of IL-1Ra, even in response to IL-1beta, suggesting that chondrocytes
      produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the
      effect of IL-1beta, while dexamethasone prevented the response. We observed by RT
      PCR that IL-1beta and IL-6 induced primarily the production of sIL-1Ra mRNA.
      Furthermore, IL-1beta alone or combined with IL-6 increased the levels of nascent
      unspliced sIL-1Ra mRNA, suggesting that sIL-1Ra expression is regulated at the
      transcriptional level. Reporter gene assays in immortalized chondrocytes, C
      20/A4, consistently showed increased sIL-1Ra promoter activity in response to IL
      1beta and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in
      response to IL-1beta and IL-6. The production of sIL-1Ra by chondrocytes may have
      a protective effect against articular inflammatory and catabolic responses.

PMID- 12010577
TI  - Encephalomeningocele cases over 10 years in Thailand: a case series.
AB  - BACKGROUND: Encephalomeningocele, especially in the frontoethmoidal region, is a
      form of neural tube defect which affects patients in Southeast Asia more commonly
      than in Western countries. Its underlying cause is not known but teratogenic
      environmental agents are suspected. However, nutritional deficiency, as in spina
      bifida, cannot be excluded. METHODS: This study reports 21 cases of meningocele
      (without brain tissue in the lesion) and encephalomeningocele (with brain tissue)
      that were admitted to our hospital for surgical corrections in the period of ten
      years, from 1990 to 1999. Clinicopathological findings, as well as occupations of
      family members and prenatal exposures to infectious agents or chemicals were
      reviewed and analyzed. RESULTS: The most commonly involved area was the
      frontoethmoidal region, found in 20 cases. The combined pattern between
      nasoethmoidal and nasoorbital defects was found most frequently (11 from 21
      cases) and had more associated abnormalities. Encephalomeningocele had more
      related abnormalities than meningocele with proportions of 0.6 and 0.3,
      respectively. CONCLUSIONS: Here, we confirmed that genetic defects are not likely
      to be the single primary cause of this malformation. However, we could not draw
      any conclusions on etiologic agents. We suggest that case control studies and
      further investigation on the role of nutritional deficiencies, especially folic
      acid, in the pathogenesis of encephalomeningocele are necessary to clarify the
      underlying mechanisms.

PMID- 12010576
TI  - Types of inter-atomic interactions at the MHC-peptide interface: identifying
      commonality from accumulated data.
AB  - BACKGROUND: Quantitative information on the types of inter-atomic interactions at
      the MHC-peptide interface will provide insights to backbone/sidechain atom
      preference during binding. Qualitative descriptions of such interactions in each
      complex have been documented by protein crystallographers. However, no
      comprehensive report is available to account for the common types of inter-atomic
      interactions in a set of MHC-peptide complexes characterized by variation in MHC
      allele and peptide sequence. The available x-ray crystallography data for these
      complexes in the Protein Databank (PDB) provides an opportunity to identify the
      prevalent types of such interactions at the binding interface. RESULTS: We
      calculated the percentage distributions of four types of interactions at varying
      inter-atomic distances. The mean percentage distribution for these interactions
      and their standard deviation about the mean distribution is presented. The
      prevalence of SS and SB interactions at the MHC-peptide interface is shown in
      this study. SB is clearly dominant at an inter-atomic distance of 3A. CONCLUSION:
      The prevalently dominant SB interactions at the interface suggest the importance
      of peptide backbone conformation during MHC-peptide binding. Currently, available
      algorithms are developed for protein sidechain prediction upon fixed backbone
      template. This study shows the preference of backbone atoms in MHC-peptide
      binding and hence emphasizes the need for accurate peptide backbone prediction in
      quantitative MHC-peptide binding calculations.

PMID- 12010578
TI  - Effects of dietary oxysterols on coronary arteries in hyperlipidaemic hamsters.
AB  - The aim of this study was to evaluate the effect of dietary oxysterols on
      coronary atherosclerosis and vasospasm. Golden Syrian hamsters were fed three
      diets with different lipid contents for 3 months: (1) a normolipidaemic diet
      containing 25 g corn oil-fish oil (4:1, w/w)/kg (group Low L); (2) a
      hyperlipidaemic diet composed of the normolipidaemic diet supplemented with 150 g
      lard+30 g cholesterol/kg (group High L); (3) a third diet, similar to the
      hyperlipidaemic diet, in which 4 g cholesterol/kg was replaced by a mixture of
      oxysterols (group High L+OS). The oxysterol mixture contained (g/kg): 5,6alpha
      epoxycholesterol 211, 5,6beta-epoxycholesterol 179, 7alpha-hydroxycholesterol 67,
      7beta-hydroxycholesterol (7betaOH) 185, 7-ketocholesterol (7 K) 235; and trace
      amounts of 7-hydroperoxycholesterols (approximately 30 g/kg). Atherosclerosis was
      evaluated by measuring myocardial Ca, oxysterols and acyl-CoA cholesterol acyl
      transferase (ACAT) activity; furthermore, coronary reactivity to sodium
      nitroprusside was measured and the morphology of coronary arteries was visualized
      by transmission electron microscopy. Coronary spasm was determined by evaluating
      reactivity to serotonin. Feeding the high-lipid diet (group High L) increased the
      plasma level of 7betaOH, 7 K and cholestanetriol. The presence of oxysterols in
      the diet (group High L+OS) further increased the concentrations of 7betaOH and 7
      K in the plasma. However, as evidenced by myocardial Ca, ACAT activity and
      coronary reactivity to sodium nitroprusside, severe atherosclerosis did not
      develop during the 3-month diet. 7 K was increased in myocardial lipids of groups
      High L and High L+OS. Electron microscopy did not show the development of
      atherosclerosis in group High L, whereas vascular wall thickening, endothelial
      damage and smooth muscle cell proliferation and migration occurred when
      oxysterols were present in the food. Serotonin induced exacerbated coronary
      vasoconstriction in group High L that was completely reversed by dietary
      oxysterols. In conclusion, dietary oxysterols exhibit anti-spasmodic properties,
      but they cannot be used as agents against excess dietary lipid-induced coronary
      spasm because of their atherogenic properties.

PMID- 12010579
TI  - The immune system as a physiological indicator of marginal copper status?
AB  - Cu appears to have many important functional roles in the body that apparently
      relate, among others, to the maintenance of immune function, bone health and
      haemostasis. Some have suggested a role for long-term marginal Cu deficiency in
      the aetiology of a number of degenerative diseases. Accurate diagnosis of
      marginal Cu deficiency, however, has remained elusive despite an increased
      understanding of the biochemistry of Cu and its physiological roles in the body.
      Traditional markers of Cu status, such as serum Cu and caeruloplasmin protein
      concentrations are insensitive to subtle changes in Cu status. Cu-containing
      enzymes, such as Cu-Zn-superoxide dismutase, cytochrome c oxidase and diamine
      oxidase, may be more reliable but evidence to date is not conclusive. Development
      of markers sensitive to marginal Cu status is essential before conclusions can be
      drawn concerning the risks of long-term intake of suboptimal dietary Cu. As Cu
      appears to be essential for maintenance of immune function, activities of
      specific immunological markers, altered in Cu deficiency, offer alternatives.
      This review evaluates a selection of immunological markers that could be
      considered potentially sensitive markers of marginal Cu status. The indices of
      immune function reviewed are neutrophil function, interleukin 2 production,
      blastogenic response to mitogens and lymphocyte subset phenotyping.

PMID- 12010580
TI  - Intestinal microflora of human infants and current trends for its nutritional
      modulation.
AB  - Diet, among other environmental and genetic factors, is currently recognised to
      have an important role in health and disease. There is increasing evidence that
      the human colonic microbiota can contribute positively towards host nutrition and
      health. As such, dietary modulation has been proposed as important for improved
      gut health, especially during the highly sensitive stage of infancy. Differences
      in gut microflora composition and incidence of infection occur between breast-
      and formula-fed infants. Human milk components that cannot be duplicated in
      infant formulae could possibly account for these differences. However, various
      functional food ingredients such as oligosaccharides, prebiotics, proteins and
      probiotics could effect a beneficial modification in the composition and
      activities of gut microflora of infants. The aim of the present review is to
      describe existing knowledge on the composition and metabolic activities of the
      gastrointestinal microflora of human infants and discuss various possibilities
      and opportunities for its nutritional modulation.

PMID- 12010581
TI  - A modified dot-blot method of protein determination applied in the tannin-protein
      precipitation assay to facilitate the evaluation of tannin activity in animal
      feeds.
AB  - Tannins have received considerable attention from animal nutritionists as
      potential agents for modifying ruminal fermentation patterns, or for exploring
      new feed resources. This group of secondary plant compounds is defined by their
      ability to form complexes with proteins. A widely accepted method for assaying
      the biological activity of extracted tannins is the precipitation of bovine serum
      albumin. The protein carries a radioactive label (125I) to allow direct
      quantification from the precipitate. Tannin-protein complexes dissolve in sodium
      dodecylsulfate solution. A dot-blot assay for protein determination, which is
      based on the reversible binding of a fluorochrome, benzoxanthene yellow, to the
      protein spots and is not disturbed by the presence of detergents, can replace the
      radioactive method by a fluorimetric measurement. A novel alternative to the last
      part of the dot-blot assay is to scan the stained protein spots in situ using a
      video camera and computer image analysis. Several filter sets were tested and,
      within a concentration range of 0.1-2.0 mg protein/ml, each of them yielded
      results identical to the original method while the time required was only 30 % of
      the working time consumed by the original procedure. The modified dot-blot assay
      should be applicable to the evaluation of tannin activity in all shrub and tree
      foliages considered as animal feed.

PMID- 12010582
TI  - Dietary fat source regulates ob gene expression in white adipose tissue of rats
      under hyperphagic feeding.
AB  - This work was designed to investigate the effect of different lipid sources on ob
      gene expression and serum leptin levels in rats with two different feeding
      protocols: (1) free access to food; or (2) energy-controlled feeding. Male Wistar
      rats were fed diets containing 40 % energy as fat (olive oil, sunflower oil or
      beef tallow), for 4 weeks. In Expt 1 rats had free access to food, and in Expt 2
      rats were fed a controlled amount of food (16 g/d, equivalent to 300 kJ/d).
      Insulin and leptin were determined by ELISA and ob mRNA by Northern blot. When
      rats had free access to food, ob mRNA levels were higher in animals fed either
      olive oil or sunflower oil than in those fed beef tallow. In marked contrast with
      feeding ad libitum, no differences were found among dietary fat groups in rats
      fed energy-controlled diets. When both feeding protocols were compared, free
      access to food induced an increased expression of ob mRNA in perirenal and/or
      epididymal adipose tissues from rats fed either olive oil or sunflower oil, but
      not from rats fed beef tallow. Dietary lipid type did not induce modifications in
      serum leptin concentrations. A tendency to higher serum leptin levels was
      observed more in rats with free access to food than in rats fed energy-controlled
      feeding. No differences were found in insulin levels. Dietary fat type
      importantly affects ob mRNA expression in rat white adipose tissue under
      hyperphagic conditions. Further study is needed in order to elucidate the
      mechanism underlying this effect.

PMID- 12010583
TI  - Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential
      associations with lipid responses.
AB  - Fish-oil supplementation can reduce circulating triacylglycerol (TG) levels and
      cardiovascular risk. This study aimed to assess independent associations between
      changes in platelet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      and fasting and postprandial (PP) lipoprotein concentrations and LDL oxidation
      status, following fish-oil intervention. Fifty-five mildly
      hypertriacylglycerolaemic (TG 1.5-4.0 mmol/l) men completed a double-blind
      placebo controlled cross over study, where individuals consumed 6 g fish oil (3 g
      EPA+DHA) or 6 g olive oil (placebo)/d for two 6-week intervention periods, with a
      12-week wash-out period in between. Fish-oil intervention resulted in a
      significant increase in the platelet phospholipid EPA (+491 %, P<0.001) and DHA
      (+44 %, P<0.001) content and a significant decrease in the arachidonic acid (-10
      %, P<0.001) and gamma-linolenic acid (-24 %, P<0.001) levels. A 30 % increase in
      ex vivo LDL oxidation (P<0.001) was observed. In addition, fish oil resulted in a
      significant decrease in fasting and PP TG levels (P<0.001), PP non-esterified
      fatty acid (NEFA) levels, and in the percentage LDL as LDL-3 (P=0.040), and an
      increase in LDL-cholesterol (P=0.027). In multivariate analysis, changes in
      platelet phospholipid DHA emerged as being independently associated with the rise
      in LDL-cholesterol, accounting for 16 % of the variability in this outcome
      measure (P=0.030). In contrast, increases in platelet EPA were independently
      associated with the reductions in fasting (P=0.046) and PP TG (P=0.023), and PP
      NEFA (P=0.015), explaining 15-20 % and 25 % of the variability in response
      respectively. Increases in platelet EPA+DHA were independently and positively
      associated with the increase in LDL oxidation (P=0.011). EPA and DHA may have
      differential effects on plasma lipids in mildly hypertriacylglycerolaemic men.

PMID- 12010584
TI  - Protein and arginine requirements for maintenance and nitrogen gain in four
      teleosts.
AB  - Besides being an indispensable amino acid for protein synthesis, arginine (Arg)
      is also involved in a number of other physiological functions. Available data on
      the quantitative requirement for Arg in different teleosts appear to show much
      variability. So far, there are very limited data on the maintenance requirements
      of indispensable amino acids (IAA) in fish. In the present study, we compared N
      and Arg requirements for maintenance and growth of four finfish species: rainbow
      trout (Oncorhynchus mykiss), turbot (Psetta maxima), gilthead seabream (Sparus
      aurata) and European seabass (Dicentrarchus labrax). Groups of fish having an
      initial body weight close to 5-7 g were fed semi-purified diets containing graded
      levels of N (0 to 8 % DM) and Arg (0 to 3 % DM) over 4 to 6 weeks. For each
      species, N and Arg requirements for maintenance and for growth were calculated
      regressing daily N gain against daily N or Arg intakes. N requirement for
      maintenance was estimated to be 37.8, 127.3, 84.7 and 45.1 mg/kg metabolic body
      weight per d and 2.3, 2.2, 2.6 and 2.5 g for 1 g N accretion, in rainbow trout,
      turbot, gilthead seabream and European seabass respectively. The four species
      studied appear to have very low or no dietary Arg requirements for maintenance.
      Arg requirement for g N accretion was calculated to be 0.86 g in rainbow trout
      and between 1.04-1.11 g in the three marine species. Turbot required more N for
      maintenance than the other three species, possibly explaining its reputedly high
      overall dietary protein requirement. Data suggest a small but sufficient
      endogenous Arg synthesis to maintain whole body N balance and differences between
      freshwater and marine species as regards Arg requirement. It is worth verifying
      this tendency with other IAA.

PMID- 12010585
TI  - beta-Carotene and alpha-tocopherol concentration and antioxidant status in buccal
      mucosal cells and plasma after oral supplementation.
AB  - The uptake of alpha-tocopherol and beta-carotene and their antioxidative effect
      in plasma and buccal mucosal cells after oral application in twelve subjects is
      demonstrated in our study. The effect on the antioxidative status was evaluated
      using a modified thiobarbituric acid-reactive substance (TBARS) method. As
      expected, the supplement of 134.2 mg alpha-tocopherol/d and 25 mg beta-carotene/d
      for 7 d resulted in a significant increase of alpha-tocopherol and beta-carotene
      concentration in plasma (P<0.05). In buccal mucosal cells, the concentration of
      beta-carotene increased after supplementation (P<0.05), whereas the concentration
      of alpha-tocopherol remained constant. A decrease in TBARS (P<0.05) was found in
      buccal mucosal cells but not in plasma. In conclusion, an uptake of the
      supplemented antioxidants was detected in plasma and in buccal mucosal cells.
      There was significant change in beta-carotene concentration and oxidative stress
      as measured using a modified TBARS test in buccal mucosal cells, but not in the
      plasma.

PMID- 12010586
TI  - High-carbohydrate-low-glycaemic index dietary advice improves glucose disposition
      index in subjects with impaired glucose tolerance.
AB  - Controversy exists about the optimal amount and source of dietary carbohydrate
      for managing insulin resistance. Therefore, we compared the effects on insulin
      sensitivity (SI), pancreatic responsivity (AIRglu) and glucose disposition index
      of dietary advice aimed at reducing the amount or altering the source of dietary
      carbohydrate in subjects with impaired glucose tolerance (IGT). Subjects were
      randomized to high-carbohydrate-high-glycaemic index (GI) (high-GI, n 11), high
      carbohydrate-low-GI (low-GI, n 13), or low-carbohydrate-high-monounsaturated fat
      (MUFA, n 11) dietary advice, with SI, AIRglu and DI measured using a frequently
      sampled, intravenous glucose tolerance test before and after 4 months treatment.
      Carbohydrate and fat intakes and diet GI, respectively, were: high-GI, 53 %, 28
      %, 83; low-GI, 55 %, 25 %, 76; MUFA, 47 %, 35 %, 82. Weight changes on each diet
      differed significantly from each other: high-GI, -0.49 (sem 0.29) kg; low-GI, 
      0.19 (sem 0.40) kg; MUFA +0.27 (sem 0.45) kg. Blood lipids did not change, but
      glycated haemoglobin increased significantly on MUFA, 0.02 (sem 0.11) %, relative
      to low-GI, -0.19 (sem 0.08) %, and high-GI, -0.13 (sem 0.14) %. Diastolic blood
      pressure fell by 8 mmHg on low-GI relative to MUFA (P=0.038). Although SI and
      AIRglu did not change significantly, DI, a measure of the ability of beta-cells
      to overcome insulin resistance by increasing insulin secretion, increased on low
      GI by >50 % (P=0.02). After adjusting for baseline values, the increase in DI on
      low-GI, 0.17 (sem 0.07), was significantly greater than those on MUFA, -0.09 (sem
      0.08) and high-GI, -0.03 (sem 0.02) (P=0.019). Thus, the long-term effects of
      altering the source of dietary carbohydrate differ from those of altering the
      amount. High-carbohydrate-low-GI dietary advice improved beta-cell function in
      subjects with IGT, and may, therefore, be useful in the management of IGT.

PMID- 12010587
TI  - Different effects of diets rich in olive oil, rapeseed oil and sunflower-seed oil
      on postprandial lipid and lipoprotein concentrations and on lipoprotein oxidation
      susceptibility.
AB  - Elevated concentrations of fasting and non-fasting triacylglycerol-rich
      lipoproteins (TRL) as well as oxidative changes of lipoproteins may increase the
      risk of ischaemic heart disease. To compare the effects of different diets rich
      in unsaturated fatty acids on the concentrations and in vitro oxidation of
      fasting and postprandial lipoproteins eighteen males consumed diets enriched with
      rapeseed oil (RO), olive oil (OO), or sunflower-seed oil (SO) in randomised order
      for periods of 3 weeks followed by a RO test meal. In the postprandial state the
      concentrations of cholesterol and triacylglycerol (TAG) in TRL were higher after
      consumption of OO compared with RO and SO (P<0.04), possibly related to
      differences in the fasting state. The propagation rates for VLDL and LDL
      oxidation were higher in the postprandial compared with the fasting state
      irrespective of diet. In the fasting state, the propagation rates were highest
      after SO (P<0.001), and in the postprandial state, SO gave rise to a shorter VLDL
      lag time (P=0.03) and a higher propagation rate than OO consumption (P=0.04).
      Overall, the SO diet resulted in a higher postprandial propagation rate of LDL
      (P<0.001) compared with RO and OO, while there was no effect of diet on LDL
      oxidation lag time. Our results suggest that RO and SO diets lower the
      postprandial cholesterol and TAG concentrations compared with OO, while RO and OO
      diets result in similar and lower in vitro susceptibility to oxidation of
      lipoproteins than SO.

PMID- 12010588
TI  - Effect of multivitamins in an effervescent preparation on the respiratory burst
      of peritoneal macrophages in mice.
AB  - The effect of regular intake of low doses of an effervescent multivitamin
      preparation on the free-radical-producing activity of murine peritoneal
      macrophages under conditions resembling a possible infection was studied in
      vitro. Initially, several groups of mice were fed a basal diet and given, for 2
      weeks, water without or with supplementation of either alpha -tocopherol,
      ascorbic acid, riboflavin or a multivitamin preparation. The supplementation
      period was followed by a 2-week wash-out time interval during which control and
      multivitamin groups received deionized water. Macrophage stimulation tests using
      chemiluminescent spectroscopy were performed at the end of the supplementation
      and wash-out periods to determine cell counts and their capacity to produce free
      radicals. Multivitamin supplementation increased the number, and the reactive
      oxygen species-producing activity, of macrophages. This effect persisted for 2
      weeks after higher doses of supplementation were stopped. Multivitamin
      supplementation lowered the steady-state free radical concentrations of liver and
      spleen as measured by electron paramagnetic resonance spectroscopy. It also
      increased the antioxidant reactivity of the same organs, while there was no
      effect on the free radical concentration and antioxidant capacity of the kidney
      and brain. When taken regularly, low doses of multivitamin supplementation may
      have a beneficial effect on the defence mechanisms of the organism.

PMID- 12010589
TI  - Energy balance of pregnant diabetic rats.
AB  - Pregnancy and diabetes lead to metabolic alterations in the energy balance that
      may not be completely independent. The objective of the present study was to look
      at the alterations induced by type 1 diabetes mellitus on the energy balance of
      pregnant rats and the offspring. Diabetes was induced by streptozotocin injection
      15 d before the starting of pregnancy. The rats had their energy balance
      variables followed for 21 d. Protein, fat and energy content of dams was
      determined from samples of the carcasses. Pregnancy led to increased energy
      intake, energy gain and energy expenditure as well as higher gross food
      efficiency than non-pregnant counterparts. Diabetes increased metabolizable
      energy intake but not the energy gain of the animals: they had very high energy
      expenditure, so that diabetes blocked the improvement in gross food efficiency
      shown during pregnancy. Offspring from diabetic dams were born with lower body
      weight. Pregnant animals did not present the usual energy storage as seen by
      lower energy gain of diabetic dams as well as by the lower fat content in the
      carcasses of pregnant diabetic rats. It is concluded that diabetes impairs the
      energy variables usually enhanced by pregnancy alone.

PMID- 12010590
TI  - The ability of habitual exercise to influence appetite and food intake in
      response to high- and low-energy preloads in man.
AB  - The present study tested the hypothesis that habitual exercisers demonstrate an
      increased accuracy of regulation of food intake in compensation for previous
      dietary energy intake. Twenty-three lean healthy male subjects were divided into
      two groups on the basis of their habitual exercise levels: non-exercisers (no
      exercise sessions/week, n 9), and exercisers (>two exercise sessions of 40 min or
      more/week, n 14). The appetite response to covert liquid preloads of high (2513
      kJ) energy (HE) and low (1008 kJ) energy (LE) was investigated Sixty minutes
      after the preload subjects were offered an ab libitum buffet-style meal and
      energy intake (EI) was calculated. Subjective hunger and satiety were assessed
      throughout using self-rated visual-analogue scales. Buffet EI in non-exercisers
      was not significantly different following the LE or HE preloads (mean
      compensation 7 %), but the exercise group significantly reduced their energy
      intake following the HE, compared with the LE, preload (mean compensation 90 %;
      P=0.0035). A broadly similar pattern of response was observed for both moderate
      (two to three sessions/week, n 7) and high exercisers (>four sessions/week, n 7).
      There were no significant differences between hunger or satiety ratings following
      HE or LE preloads for either group. However non-exercisers scored significantly
      higher on their self-ratings of hunger at the start of the study, before preload
      consumption, compared with the exercisers (P<0.01). These findings demonstrate
      that habitual exercisers have an increased accuracy of short-term regulation of
      food intake in compensation for preload manipulation, and provide additional
      support for advocating regular exercise in the prevention of overweight and
      obesity.

PMID- 12010591
TI  - Practice variation in urology.

PMID- 12010592
TI  - Survey of radiation oncologists: practice patterns of the management of stage I
      seminoma of testis in Canada and a selected group in the United States.
AB  - OBJECTIVE: To evaluate practice patterns of the management of stage I seminoma of
      testis in Canada and a selected group in the United States. MATERIALS AND
      METHODS: Survey among radiation oncologists treating genitourinary (GU) tumors in
      Canada and the RTOG GU committee members in the United States between January and
      March 2001. RESULTS: Response rate was 78% (73/93) in Canada and 67% (24/36) in
      the United States. Eighty-four percent described their clinical practice as a
      university affiliated teaching center, and 16% as community-based or private
      practice. Sixty-two percent, 31% and 7% would manage 1-5, 6-10 and > oe = 11
      cases per year respectively. Almost all would perform chest x-ray (99%) and CT
      scan of abdomen and pelvis (100%) as staging investigation following radical
      inguinal orchiectomy. Forty percent also arranged CT scan of chest, while only
      18% routinely obtained lymphangiogram. Seventy-eight percent offered surveillance
      as a management option and estimated that 20% (median) of patients would choose
      surveillance in their practice. Among four management options: (1. surveillance,
      2. radiotherapy (RT) to the para-aortic region, 3. RT to the para-aortic and
      ipsilateral pelvis ('dog-leg'), 4. single-agent chemotherapy), the order of first
      preference was option 1 (44%), 2 (42%), and 3 (14%) for patients who wish to
      preserve fertility. When fertility was not a major concern, it was option 2
      (43%), 3 (39%), and 1 (17%). The commonest dose-fractionation schedule was 25
      Gy/20 fractions (68%). Others included 25 Gy/15 f (15%), and 25.5 Gy/17 f (4%).
      Forty-five percent chose the para-aortic region, while 53% used the 'dog-leg' as
      RT volume. Twenty-nine percent reduced RT volume from the 'dog-leg' to the para
      aortic region as the result of MRC Phase III study published in 1999. CONCLUSION:
      There are significant variations in the practice pattern of the management of
      stage I seminoma of testis among radiation oncologists in Canada and a selected
      group in the United States.

PMID- 12010593
TI  - Is an artificial sphincter the best choice for incontinent boys with Spina
      Bifida? Review of our long term experience with the AS-800 artificial sphincter.
AB  - OBJECTIVE: We describe our long-term experience in a uniform population of Spina
      Bifida boys all treated with the AS-800 model artificial urinary sphincter (AUS)
      and compare our results to other treatment modalities available to children with
      neurogenic incontinence. MATERIALS AND METHODS: The complete medical records of
      30 patients with insertion of the AS-800 were reviewed. All were boys having
      Spina Bifida with only one having prior bladder neck reconstruction. The mean age
      at insertion was 12.6 years and the average follow up was 6.5 years.
      Anticholinergic agents and self-intermittent catheterization were used
      concomitantly to the AUS in 21 and 22 patients respectively. RESULTS: In our
      series, 19 (63%) patients were completely dry, 6 (20%) were slightly wet, 5 (17%)
      were incontinent. The mean lifetime of all artificial sphincters was 4.7 years
      with no statistically significant difference in survival of those inserted at the
      bladder neck and bulbar urethra (4.6 and 4.9 years respectively). However, a
      survival analysis revealed a sharp drop after 100 months with only 8.3% of the
      sphincters implanted lasting beyond this point. There were a total of 32
      revisions performed in 17 patients constituting a 0.164 revision rate/patient
      years. The other surgical treatment available to these children is bladder neck
      reconstruction with reported continence rates ranging from 61% to 76% at about 2
      years follow up. CONCLUSIONS: In our experience, the AS-800 model artificial
      sphincter has a long term survival which rarely exceeds 8 to 9 years putting into
      question whether it or bladder neck reconstruction is the best long term solution
      for treating children with neurogenic incontinence. This question may be only
      answered by a randomized, controlled trial comparing these two modalities.

PMID- 12010594
TI  - Topical steroid therapy for phimosis.
AB  - INTRODUCTION: Circumcision has been the traditional treatment for phimosis.
      Recent reports of medical management of phimosis with topical steroids quote
      success rates of 67%-95%. We present our results with topical steroid therapy for
      treatment of phimosis. MATERIALS AND METHODS: Retrospective review of 69 boys
      between the age of 3 and 13 years (average 7.4) who were referred to Urology
      clinic over a one year period (August 1999-2000) with phimosis. Boys without a
      distal preputial ring were excluded. A course of triamcinolone cream was
      prescribed and parents/patients were instructed to apply it to the preputial
      outlet twice daily for one month. Six weeks after treatment initiation patients
      were reassessed. Results were classified as follows: Full retraction (FR)-entire
      glans and coronal margin seen, Moderate retraction (MR)-proximal glans seen,
      residual preputial adhesions, Partial retraction (PR)-distal glans and meatus
      seen, and Failure (F)-no change. FR, MR, and PR were considered successful
      outcomes. Statistical analysis was performed with Splus software using the
      prop.test and ordinal logistic regression procedures. RESULTS: Follow-up ranged
      from 1-12 months, and 8 patients were lost to follow-up. Of the remaining 61
      boys, 82% (12 FR, 26 MR, 12 PR) were successfully managed with topical steroid
      (95% confidence interval: 69%-90%). Scarring on examination was observed to
      negatively impact outcome (92% versus 67%) and was statistically significant
      using ordinal logistic regression (Chi square test=4.48, p-value=0.034). Two boys
      with severe balanitis xerotica obliterans (BXO) and two boys with buried penis
      and penoscrotal webbing failed treatment and required surgery. There was an
      association noted between older age and poorer outcome but this was not
      statistically significant. There were no local or systemic side effects noted.
      CONCLUSIONS: Local application of steroid cream to the phimotic foreskin may
      allow some degree of retraction and avert the need for circumcision. Although the
      length of follow-up is insufficient to decree ultimate success, topical steroid
      appears to be a safe and effective treatment for boys over three years of age
      with evidence of a tight preputial ring. Boys with severe BXO or buried penis and
      penoscrotal webbing should be considered primarily for surgery.

PMID- 12010595
TI  - Incorrect biochemistry complicates prostate cancer management.
AB  - A man with a prostate specific antigen (PSA) of 6.1 ng/mL, a clinical stage T2b
      prostate nodule and biopsies that showed Gleason sum 6 adenocarcinoma of the
      prostate underwent a radical prostatectomy. The final pathology showed organ
      confined disease. His postoperative PSA remained elevated at 4.0 ng/mL. The PSA
      was repeated several times and was in the same range. It was re-evaluated at
      another lab facility and was unmeasurable (<0.02 ng/mL). He has an antibody that
      cross-reacts with an assay reagent causing this false reading. The most likely
      antibody is one against mouse immunoglobulin G (IgG).

PMID- 12010597
TI  - Removal of bladder stone with metal wire infrastructure.
AB  - There are reports of a wide variety of foreign materials, placed purposefully or
      inadvertantly, that have been found in the lower urinary tract. Due to
      encrustatation, some of these objects may initially appear to be simple stones. A
      careful evaluation with an appropriate index of suspicion is needed to aid in the
      determination of whether one of these complex structures may be present. A
      determination of the composition of the structure will allow the surgeon to
      employ the most safe and expeditious means of removal. We report a case of a
      large bladder stone with a metal wire infrastructure that was removed by open
      cystolithotomy

PMID- 12010596
TI  - Epididymal metastasis from gastric signet ring cell adenocarcinoma.
AB  - We report a 55 year old man complaining of painless left testicular swelling that
      developed over 2 months. The imaging studies revealed an epididymal mass separate
      from the testicle. The patient underwent left radical orchiectomy. The
      histopathological examination of the orchiectomy specimen revealed poorly
      differentiated signet cell metastatic adenocarcinoma.

PMID- 12010598
TI  - High prevalence of giardiasis and stronglyloidiasis among HIV-infected patients
      in Bahia, Brazil.
AB  - Diarrhea due to intestinal microbial infections is a frequent manifestation among
      HIV-infected patients. It has been postulated that HIV-infected patients may have
      special types of intestinal infections, and that immune activation from such
      parasites may affect the progression of HIV disease. To evaluate these
      associations, the frequency of infections was examined in HIV-infected patients
      in Bahia, Brazil. To determine the potential impact of the presence of intestinal
      parasitic infections on HIV disease progression, a retrospective study approach
      was used. The medical charts of 365 HIV-infected patients who had been treated at
      the AIDS Clinic of the Federal University of Bahia Hospital were reviewed, and
      the prevalence of parasites was compared with 5,243 HIV-negative patients who had
      attended the hospital during the same period of time. Among HIV-infected
      subjects, CD(4) count, RNA plasma viral load (VL), and number of eosinophils were
      compared according to their stool examination results. The overall prevalence of
      each parasite was similar for HIV-positive and HIV-negative patients. However,
      the prevalence of S. stercoralis (p<10(-7)) and G. lamblia (p=0.005) was greater
      for HIV-infected subjects. The mean CD(4) count and viral load of HIV patients in
      our clinic who had stool examinations was 350 cells +/- 340 and 4.4 +/- 1.4 log
      RNA viral load, respectively. In this patient group there was no clear
      association between the level of the absolute CD(4) count or the viral load and a
      specific parasitic infection. The presence of an intestinal parasitic infection
      was not associated with faster progression of the HIV disease among HIV-infected
      patients. We conclude that strongyloidiasis and giardiasis are more frequent in
      HIV-infected patients in Bahia, Brazil. If this association is due to immune
      dysregulation, as has been proposed elsewhere, it must occur in patients after
      only minor shifts in CD(4) count from normal levels, or as a result of immune
      dysfunction not represented by CD(4) count. These infections do not appear to
      alter the progression of HIV disease.

PMID- 12010599
TI  - Compositional changes of PBL population in patients with chronic hepatitis B
      virus infection.
AB  - In this report we have analysed the peripheral blood lymphocyte of several
      patients with chronic hepatitis B virus infection with flow cytometry. Based on
      the presence and absence of the HBeAb, patients were divided into two groups. In
      both, all the patients were HBsAg positive with normal range of serum alanine
      aminotranferase (23.9 +/- 17.8). We have found that the immunophenotypic profiles
      of patients were different from healthy donors with significant decrease in
      CD(3)(+) T cells, specially CD(8)(+) T cells and a significant increase in the
      CD(19)(+) B cells. The differences were seen in other subset of T cells
      (CD(4)(+)) or NK cells (CD(56)(+)/CD(16)(+)) and HLA-DR markers were not
      significant. When the phenotypic profiles of both groups were compared with each
      other, such changes were more dominant in group II, with HBeAb positive than in
      group I, with HBeAb negative. Also, we have seen a correlation between the
      increase of CD(19)(+) B cells and the decrease of CD CD(3)(+) T cells. No such
      correlation was observed with other cells.

PMID- 12010600
TI  - Mycobacterium simiae infection in a patient with acquired immunodeficiency
      syndrome.
AB  - Mycobacterium simiae is usually an environmental contaminant rarely associated
      with human disease. We report a fatal case of M.simiae infection in a 37 year
      old, HIV positive, male from whom the organism was isolated from blood culture.
      The identification of M.simiae was performed using DNA amplification followed by
      analysis on 3% agarose gel of the amplicon fragments after digestion by
      restriction endonucleases. The precise identification of mycobacterial isolates
      to the species level is important, with both epidemiological and therapeutic
      implications.

PMID- 12010601
TI  - Bilateral endogenous endophthalmitis associated with infective endocarditis: case
      report.
AB  - Bilateral endogenous endophthalmitis is a rare condition initiated by infection
      by microbes in the bloodstream, such as those arising from a foci of infective
      endocarditis. We report a case and discuss the diagnostic aspects and the
      clinical outcome of a patient with characteristic findings of the disease. The
      patient was a 49 year old white male who had a metallic aortic valve implanted 7
      months previously, and who presented to the hospital with 10 days of fever, cough
      and dyspnea, then diarrhea and mental confusion. On the second day of
      hospitalization, he experienced sudden loss of vision in both eyes. A Gram
      positive coccobacillus was isolated from the bloodstream, he was treated with
      fluoroquinolone with disappearance of fever, decreased ocular inflammation, and
      improvement in his vision to light perception. He later underwent valve
      replacement surgery but died during the procedure. We review the occurrence of
      ocular signs and symptoms and their importance in patients with endocarditis.

PMID- 12010602
TI  - Predicting outcomes in early rheumatoid arthritis.

PMID- 12010603
TI  - Genetics in rheumatoid arthritis.
AB  - The data from the human genome project were published in 2001. Although this
      achievement will boost research in the genetics of rheumatoid arthritis (RA),
      most of the work is in progress. Three of the four consortia that are performing
      linkage studies to identify loci that are transmitted more often to patients than
      controls have published data on genome-wide searches in few families. Of all the
      possible candidate genes, the human leukocyte antigen (HLA) class II region was
      found in the pan-European and the US linkage studies, confirming the previous
      data from association studies that HLA class II alleles confer risk to RA.
      Although HLA as a risk factor for RA has been known for a long time, the
      mechanism by which HLA alleles affect disease risk are controversial. Several
      papers have been published recently that support the RA-protection hypothesis.
      Several candidate loci/genes have been suggested from association studies.
      However, these associations have not been reproduced by different groups in
      several different cohorts.

PMID- 12010604
TI  - Role of nuclear factor kappaB in synovial inflammation.
AB  - The evaluation of molecular pathways has revealed novel insights into the
      pathophysiology of rheumatoid arthritis in the last several years. Gene
      transcription factors such as nuclear factor kB (NFkB) are activated by
      extracellular signals or cell-to-cell interactions that are converted into
      intracellular activation signals through receptor molecules located in the cell
      membrane. The number of known genes being translated after NFkB activation is
      increasing steadily. These genes includes cytokines, chemokines, growth factors,
      cellular ligands, and adhesion molecules. Because many of these genes are part of
      the pathogenesis of RA, there is considerable interest in the evaluation of the
      synovium-specific effects of NFkB to unveil its potential for future therapeutic
      strategies. The goal is to evolve these strategies from the therapies that have a
      wide spectrum of effects and side effects into rheumatoid arthritis-specific
      therapies designed to inhibit distinct molecular pathways within the synovium.

PMID- 12010605
TI  - Cytokines in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease characterized by synovial
      inflammation that leads to the destruction of cartilage and bone. In the last
      decade, there was a lot of successful research in the field of cytokine
      expression and regulation. It has become clear that pro- and anti-inflammatory
      cytokines, derived predominantely from cells of macrophage lineage, play a major
      role in the initiation and perpetuation of the chronic inflammatory process in
      the RA synovial membrane. Monokines are abundant in rheumatoid synovial tissue,
      whereas low amounts of lymphokines are found. The involvement of pro-inflammatory
      cytokines, particularly interleukin (IL)-1 and tumor necrosis factor-alpha, in
      the pathogenesis of RA is well accepted. Recent data provide evidence that the
      pro-inflammatory cytokine IL-18 plays a crucial role in the development and
      sustenance of inflammatory joint diseases. There also appears to be a
      compensatory anti-inflammatory response in RA synovial membrane. It has become
      clear in the last few years that T cell-derived cytokines expressed
      preferentially by Th1 cells contribute to joint destruction and inflammation in
      RA. However, products from Th2 cells may be protective.

PMID- 12010606
TI  - Glucocorticoid use in rheumatoid arthritis.
AB  - More than 50 years after their discovery, glucocorticoids continue to be a
      mainstay of treatment for many patients with rheumatoid arthritis (RA). Although
      the short- and moderate-term efficacy of glucocorticoids in RA is seldom debated,
      increasing evidence favors a disease-modifying role of glucocorticoids. Despite
      renewed enthusiasm based on this newer long-term data, glucocorticoid use is
      marred substantially by the potential for many serious adverse events.
      Glucocorticoid-induced osteoporosis is one of the most predictable and serious
      complications for many chronic and some acute users. The correct identification
      of patients at high risk for bone complications and the institution of
      appropriate preventive measures may partially attenuate this adverse outcome.

PMID- 12010607
TI  - Pathogenesis of bone lesions in rheumatoid arthritis.
AB  - Histopathologic characterization of bone erosions from patients with rheumatoid
      arthritis (RA) and studies performed in animal models of inflammatory arthritis
      provide strong evidence that osteoclasts play an important role in focal marginal
      and subchondral bone loss in inflammatory arthritis. Much has been learned
      concerning the factors responsible for the induction and activation of
      osteoclasts associated with the bone erosions in RA. Therapies that target these
      osteoclast-inducing factors or other aspects of osteoclast-mediated bone
      resorption represent potential targets for blocking or at least attenuating bone
      destruction in RA. The demonstration of the role of the newly described
      osteoclastogenic factor receptor activator of nuclear factor kappaB ligand in RA
      synovial tissues and the successful prevention of bone erosions in animal models
      of arthritis with its inhibitor osteoprotegerin provide hope that specific
      therapies can be developed for preventing bone and joint destruction in RA,
      particularly in situations in which disease-modifying agents are ineffective in
      controlling disease activity.

PMID- 12010609
TI  - Pseudogout, hypomagnesemia, and liver transplantation.

PMID- 12010608
TI  - Lessons from animal models of arthritis.
AB  - There is increasing thought that autoantibodies to systemic self-antigens may
      provide a principal effector mechanism for the initiation and propagation of
      joint inflammation. The recent identification of arthritis transfer with
      antibodies to the self-antigen glucose-6-phosphate isomerase has boosted this
      interest. Fc receptor involvement in arthritis has been evaluated, identifying
      pro-inflammatory and inhibitory Fc gamma receptor subtypes, and demonstrating a
      link between Fc gamma receptor expression, cytokine production, cartilage
      destruction, and mouse strain susceptibility to immune complex arthritis. Further
      proof of a key role of interleukin (IL)-1 in arthritis was provided by the
      occurrence of spontaneous arthritis in IL-1 receptor antagonist knockout mice and
      elicitation of full-blown arthritis in tumor necrosis factor (TNF)-deficient
      mice. IL-18 (part of the IL-1 family) is a crucial upstream cytokine that, with
      IL-12, induces IL-1 and TNF and promotes arthritis and T-cell differentiation. IL
      18 neutralization improved arthritis outcome, but its central role in host
      defense against bacterial infections may complicate therapeutic IL-18 targeting.
      T helper 1 (Th1) cells may aggravate arthritis and joint destruction through the
      production of IL-17, which shows joint destructive potential independent of IL-1.
      Studies have also focused on the control of receptor activator of nuclear factor
      kappaB ligand, modulation with IL-4, and regulation of downstream mediators in
      tissue destruction. Gene therapeutic approaches proved efficacious and will
      provide future ways to control arthritis.

PMID- 12010610
TI  - Pathogenesis of cartilage calcification: mechanisms of crystal deposition in
      cartilage.
AB  - Apatite crystals form in physiologically calcified tissues, including the hyaline
      cartilage of the epiphyseal growth plate. While apatite crystals appear as
      unwanted deposits in other cartilage sites, more frequently, crystalline
      materials other than or in addition to apatite develop in dystrophic cartilage
      deposits. These crystalline materials include calcium pyrophosphate dihydrate and
      other calcium phosphate and calcium carbonate phases, monosodium urate, calcium
      oxalate, cholesterol, and crystallized proteins. This review describes the
      physical chemistry of crystal deposition and the events that occur in the growth
      plate as a basis for understanding the pathogenesis of nonphysiologic crystal
      deposition in cartilage.

PMID- 12010611
TI  - Update on colchicine and its mechanism of action.
AB  - Colchicine is a unique anti-inflammatory drug with respect to its limited
      clinical usefulness and its mode of action. Colchicine is mainly indicated for
      the treatment and prophylaxis of gout and familial Mediterranean fever. Its mode
      of action includes modulation of chemokine and prostanoid production and
      inhibition of neutrophil and endothelial cell adhesion molecules by which it
      interferes with the initiation and amplification of the joint inflammation. This
      paper discusses its adverse effects and indications.

PMID- 12010612
TI  - Oxalate crystal deposition disease.
AB  - In addition to monosodium urate, calcium pyrophosphate dihydrate, and apatite
      crystals, oxalate crystals are less often found in synovial fluids in association
      with acute or chronic arthritis. Oxalate crystal deposition disease is seen in
      patients with primary hyperoxaluria types 1 and 2 (PH1 and 2) and in patients
      with end-stage renal disease managed with long-term dialysis. Oxalate crystal
      deposits are found mainly in kidneys, bone, skin, and vessels, and less often
      inside the joints. Musculoskeletal and systemic manifestations of oxalate crystal
      deposition disease may be confused with those observed with the other most common
      types of crystal deposition diseases. Clinical and radiographic features include
      calcium oxalate osteopathy, acute and chronic arthropathy with chondrocalcinosis,
      synovial calcification, and miliary skin calcium oxalate deposits and vascular
      calcifications that affect mainly the hands and feet. Systemic life-threatening
      cardiovascular, neurologic, and hematologic manifestations are rare. Genomic DNA
      studies have identified those genetic defects of PH1 and PH2 that allow a precise
      early diagnosis. Kidney transplantation has poor outcome as a result of graft
      oxalosis. Combined liver and kidney transplantation is the treatment of choice in
      patients with PH1 and advanced renal failure. Pre-emptive isolated liver
      transplantation is the preferred treatment in patients who develop the disease
      during infancy with progressive manifestations of oxalosis. These novel findings
      in the understanding of the molecular and enzymatic aspects of primary
      hyperoxalurias have provided a more rational basis for the management and
      prevention of oxalate crystal deposition disease. This information may lead to a
      better understanding and effective management of other common calcium-containing
      crystal deposition diseases.

PMID- 12010613
TI  - Articular cartilage calcification and matrix vesicles.
AB  - There has been much research in calcium-containing crystal deposition diseases of
      hereditary and sporadic type. Synovial cell-induced inflammation and secondary
      cartilage damage are common in these diseases. In most cases of these diseases
      and in primary osteoarthritis, there are mineral deposits in the cartilage,
      mineral crystals in the synovial fluid, and aberrations of pyrophosphate
      metabolism.

PMID- 12010614
TI  - Pathogenesis of hyperuricemia: recent advances.
AB  - The literature on the pathogenesis of hyperuricemia have been limited to the
      discussion of metabolic syndromes associated with risk factors for
      atherosclerosis and hyperuricemia and the genetics of the juvenile form of
      hyperuricemic nephropathies. A few new mutations in the hypoxanthine-guanine
      phosphoribosyltransferase gene, which result in Lesch-Nyhan syndrome, have been
      described. In addition, some new insight has been gained in the renal handling of
      uric acid by the human kidney.

PMID- 12010615
TI  - Endoscopic treatment of gastroesophageal reflux disease--fact or fancy?

PMID- 12010617
TI  - Radiographic evaluation of complex dysphagic patients: comparison with
      videoendoscopic technique.
AB  - Swallowing is a highly coordinated sequence of physiologic events. Many disease
      processes affect the patient's ability to have a functional swallow. The
      traditional videofluoroscopic swallowing study is an effective and established
      method for evaluating these patients and is the current examination of choice.
      Videoendoscopic evaluation is a safe and affordable procedure that can be used in
      an outpatient or office setting. It can also be a complementary technique,
      allowing direct visualization of pharyngeal structures and aspiration. We discuss
      the use of both techniques.

PMID- 12010619
TI  - Endoscopic therapies for gastroesophageal reflux disease.
AB  - Although medical and surgical treatments are available for gastroesophageal
      reflux disease, endoscopic therapies for this condition are relatively new. This
      review describes the principles behind such treatments as well as the individual
      procedures themselves, focusing on mechanisms of action, safety and tolerability,
      and efficacy in animal and human clinical trials. Future trends in endoscopic
      therapy are discussed.

PMID- 12010618
TI  - Presbyesophagus: a reappraisal.
AB  - The gastrointestinal tract undergoes change with aging, and the esophagus is not
      exempt from those changes. Failure of peristalsis in the older esophagus was
      labeled "presbyesophagus" over 35 years ago. Modern manometric techniques and
      classification systems have challenged this concept, yet there are clearly age
      related changes in the esophagus. The lower esophageal sphincter changes little.
      Esophageal peristalsis (body) is more likely to fail in older patients, but some
      of this failure may be caused by damage from gastroesophageal reflux disease. The
      pharynx and upper esophageal sphincter also undergo age-related changes in health
      and disease. The ability to sense events in the esophagus fails with aging, which
      may cause patients with severe mucosal disease to present with less severe
      symptoms. Failure of the esophagus thus does not appear to be an inevitable
      consequence of aging, but the esophagues does undergo change with aging, and
      these changes should be considered in evaluation of older patients with
      esophageal complaints.

PMID- 12010620
TI  - Esophageal manifestations of dermatologic disease.
AB  - This review describes those skin conditions, or conditions where skin involvement
      is a prominent feature, that may present with esophageal manifestations. These
      conditions have been categorized in many different ways. For the purposes of this
      review, esophageal manifestations of skin conditions are classified as bullous
      diseases, hyperkeratotic diseases, collagen vascular diseases, syndromes
      associated with cancer, and miscellaneous diseases.

PMID- 12010621
TI  - Unsedated transnasal endoscopy: a safe and less costly alternative.
AB  - Upper endoscopy is an integral component in the management of upper
      gastrointestinal disorders, but it is underutilized because of its high cost and
      potential complications. Unsedated transnasal endoscopy (T-EGD) is a relatively
      new technique using an ultrathin endoscope. Because it is better tolerated than
      standard upper endoscopy, it is performed with the patient unsedated, thus
      avoiding the associated costs and complications of conscious sedation. In this
      review, the technique of T-EGD and its current experience are discussed. In
      addition, potential future applications, special considerations, and potential
      pitfalls are reviewed.

PMID- 12010622
TI  - Pharmacologic management of gastroesophageal reflux disease.
AB  - The burden of gastroesophageal reflux disease (GERD) results from its widespread
      prevalence and the unfavorable impact of its symptoms on well-being and quality
      of life. Whereas abnormalities of the antireflux barrier (lower esophageal
      sphincter) are important in the pathophysiology of GERD, pharmacologic therapy
      for GERD is based on suppression of acid, which is responsible for the majority
      of the symptoms and for epithelial damage. Proton pump inhibitors (PPIs) are the
      agents of choice for achieving the goals of medical therapy in GERD, which
      include symptom relief, improvement in quality of life, and healing and
      prevention of mucosal injury. As a class, these drugs are extremely safe. The
      newest PPI, esomeprazole, brings a statistically significant increase in healing
      of mucosal injury and symptom relief in patients with erosive esophagitis,
      compared with omeprazole and lansoprazole. This article reviews the role of
      medical therapy in the short- and long-term management of symptomatic patients
      with or without erosive esophagitis, including extraesophageal presentations,
      GERD during pregnancy, and Barrett's esophagus. Management of refractory patients
      is addressed.

PMID- 12010623
TI  - Erythromycin and gastroduodenal contractile activity.

PMID- 12010624
TI  - The surgical management of short bowel syndrome.
AB  - Short bowel syndrome is a clinical entity that results from a diverse group of
      congenital and acquired conditions in the pediatric population. The
      pathophysiology of this syndrome is characterized by malabsorption, malnutrition,
      and metabolic disturbances. The vast majority of children with this condition
      undergo spontaneous adaptation of the intestinal remnant and achieve enteral
      nutritional autonomy. However, a small portion of pediatric patients develop
      intestinal failure and require long-term or permanent dependence on total
      parenteral nutrition. These children may benefit from surgical interventions that
      facilitate intestinal adaptation. Such adjunctive procedures facilitate nutrient
      absorption by improving motility, prolonging intestinal transit, and/or
      increasing mucosal contact time. In selected patients, this may allow them to be
      weaned from parenteral nutritional support or to have it discontinued. The
      purpose of this review is to discuss the various surgical techniques for the
      management of short bowel syndrome in children, along with their indications,
      complications, and outcomes.

PMID- 12010625
TI  - New developments in childhood celiac disease.
AB  - Celiac disease (CD) is one of the most common lifelong disorders in Europe and
      the United States, in both children and adults. It is an immune-mediated
      enteropathy triggered by the ingestion of gluten in genetically susceptible
      individuals. This review addresses new developments in CD with respect to
      pediatric patients and emphasizes the need for awareness among health-care
      professionals. The epidemiology, pathophysiology, diagnosis, and clinical
      spectrum of CD in children are highlighted.

PMID- 12010626
TI  - Perspectives on childhood obesity.
AB  - The high prevalence of overweight and obesity in children in the United States
      over the past 30 years makes it a topic of great interest. This article reviews
      the current understanding of childhood obesity, including its causes, effects,
      persistence into adulthood, and treatment. Societal and familial influences are
      addressed, as well as genetic factors.

PMID- 12010627
TI  - Autism and gastrointestinal symptoms.
AB  - Autism is a collection of behavioral symptoms characterized by dysfunction in
      social interaction and communication in affected children. It is typically
      associated with restrictive, repetitive, and stereotypic behavior and manifests
      within the first 3 years of life. The cause of this disorder is not known. Over
      the past decade, a significant upswing in research has occurred to examine the
      biologic basis of autism. Recent clinical studies have revealed a high prevalence
      of gastrointestinal symptoms, inflammation, and dysfunction in children with
      autism. Mild to moderate degrees of inflammation were found in both the upper and
      lower intestinal tract. In addition, decreased sulfation capacity of the liver,
      pathologic intestinal permeability, increased secretory response to intravenous
      secretin injection, and decreased digestive enzyme activities were reported in
      many children with autism. Treatment of digestive problems appears to have
      positive effects on autistic behavior. These new observations represent only a
      piece of the unsolved autism "puzzle" and should stimulate more research into the
      brain-gut connection.

PMID- 12010628
TI  - Use of electrogastrography in children.
AB  - Electrogastrography (EGG), the measurement of gastric pacemeaker activity by
      means of surface electrodes, provides a noninvasive technique to detect and
      quantify the characteristics of the gastric slow wave. With a predominant
      frequency of three cycles per minute, the activity of the specialized cells
      responsible for this pacing, the interstitial cells of Cajal, is crucial in
      providing the underlying electrophysiologic changes that enable coordinated
      smooth muscle contraction and synchronized peristalsis. Advances in electronics
      and software to define frequency distribution, stability of the signal,
      postprandial changes, and other parameters have contributed to more widespread
      interest in EGG and its application to the investigation of functional
      gastrointestinal disturbances. Definition of pediatric norms and postnatal
      changes in the EGG of premature infants has provided the foundation for further
      studies investigating correlative changes with such important functions as
      gastric emptying and motility. The EGG remains a promising diagnostic tool.
      Future studies will help define its usefulness in identifying abnormal functions
      of the interstitial cells of Cajal.

PMID- 12010629
TI  - Possible new mechanism of cortisol action in female reproductive organs:
      physiological implications of the free hormone hypothesis.
AB  - The so-called free hormone hypothesis predicts that the biological activity of a
      given steroid correlates with the free protein-unbound concentration rather than
      with the total concentration (i.e. free plus protein-bound). Cortisol is a
      glucocorticoid with many diverse functions and the free hormone hypothesis seems
      to apply well to the observed effects of cortisol. The ovaries express
      glucocorticoid receptors and are affected by cortisol, but lack the necessary
      enzymes for cortisol synthesis. Ovarian follicles modulate the biological
      activity of cortisol by (1) follicular production of especially progesterone and
      17 alpha-hydroxy-progesterone which, within the follicle, reach levels that
      displace cortisol from its binding proteins, in particular, cortisol-binding
      protein, making it available for biological action and (2) a developmental
      regulated expression of two types of 11 beta-hydroxysteroid dehydrogenase (i.e.
      11 beta-HSD type 1 and type 2), which oppose the action of one another, the 11
      beta-HSD type 2 predominantly inactivating cortisol to cortisone, while 11 beta
      HSD type 1 reverses this reaction. As a result, a high concentration of cortisol
      available for biological action is present in the preovulatory follicle just
      prior to ovulation and it has been suggested that cortisol may function to reduce
      the inflammatory-like reactions occurring in connection with ovulation. This
      paper suggests (1) that the function of the oviduct is also affected by the high
      levels of free cortisol released in preovulatory follicular fluid at ovulation
      and (2) that formation and function of the corpus luteum benefits from a high
      local concentration of free cortisol, whereas the surrounding developing
      follicles may experience negative effects. If this hypothesis proves correct it
      may describe a new physiological mechanism by which cortisol interacts with the
      female reproductive organs, showing that the biologically active concentration of
      a steroid locally can be regulated to serve specific functions.

PMID- 12010630
TI  - Roles of prolactin and related members of the prolactin/growth hormone/placental
      lactogen family in angiogenesis.
AB  - Prolactin, growth hormone and placental lactogen are members of a family of
      polypeptide hormones which share structural similarities and biological
      activities. Numerous functions have been attributed to these hormones, among
      which stand out their recently discovered effects on angiogenesis, the process by
      which new blood vessels are formed from the pre-existing microvasculature.
      Prolactin, growth hormone and placental lactogen, along with two non-classical
      members of the family, proliferin and proliferin-related protein, can act both as
      circulating hormones and as paracrine/autocrine factors to either stimulate or
      inhibit various stages of the formation and remodeling of new blood vessels,
      including endothelial cell proliferation, migration, protease production and
      apoptosis. Such opposing actions can reside in similar but independent molecules,
      as is the case of proliferin and proliferin-related protein, which stimulate and
      inhibit angiogenesis respectively. The potential to exert opposing effects on
      angiogenesis can also reside within the same molecule as the parent protein can
      promote angiogenesis (i.e. prolactin, growth hormone and placental lactogen), but
      after proteolytic processing the resulting peptide fragment acquires anti
      angiogenic properties (i.e. 16 kDa prolactin, 16 kDa growth hormone and 16 kDa
      placental lactogen). The unique properties of the peptide fragments versus the
      full-length molecules, the regulation of the protease responsible for specific
      protein cleavage, the selective expression of specific receptors and their
      associated signal transduction pathways are issues that are being investigated to
      further establish the precise contribution of these hormones to angiogenesis
      under both physiological and pathological situations. In this review article, we
      summarize the known and speculative issues underlying the effects of the
      prolactin, growth hormone and placental lactogen family of proteins on
      angiogenesis, and address important remaining enigmas in this field of research.

PMID- 12010631
TI  - Ghrelin in neonatal rats: distribution in stomach and its possible role.
AB  - Ghrelin, a 28 amino acid peptide, has recently been isolated from the rat stomach
      as an endogenous ligand for the GH secretagogue receptor. The fact that
      administration of ghrelin, centrally or peripherally, stimulates both food intake
      and GH secretion suggests that stomach ghrelin has an important role in the
      growth of rats. We used immunohistochemistry and radioimmunoassay to determine
      the age at which ghrelin-immunostained cells begin to appear in the rat stomach.
      Ghrelin-immunoreactive cells were found to be expressed in the fetal stomach from
      pregnancy day 18. The number of ghrelin-immunoreactive cells in the fetal stomach
      increased as the stomach grew. The amount of ghrelin in the glandular part of the
      rat stomach also increased, in an age-dependent manner, from the neonatal stage
      to adult. Eight hours of milk restriction significantly decreased the ghrelin
      concentration in the stomachs of 1-week-old rats, and increased the ghrelin
      concentration in their plasma. Administration of ghrelin to 1- and 3-week-old
      rats increased plasma GH concentrations. The daily subcutaneous administration of
      ghrelin to pregnant rats from day 15 to day 21 of pregnancy caused an increase in
      body weight of newborn rats. In addition, daily subcutaneous administration of
      ghrelin to neonatal rats from birth advanced the day of vaginal opening from day
      30.7+/-0.94 to day 27.9+/-0.05. These results suggest that ghrelin may be
      involved in neonatal development.

PMID- 12010632
TI  - Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat
      cardiomyocytes: effects of metabolites and analogs.
AB  - Cellular and nuclear uptake of [125I]tri-iodothyronine (T3) and
      [125I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day
      old rats, and the effect of thyroid hormone analogs on cellular T(3) uptake was
      measured. Cells (5-10 x 10(5) per well) were cultured in DMEM-M199 with 5% horse
      serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37
      degrees C in the same medium, 0.5% BSA and [125I]T3 (100 pM), or [125I]Triac (240
      pM). Expressed as % dose, T(3) uptake was five times Triac uptake, but expressed
      as fmol/pM free hormone, Triac uptake was at least 30% (P<0.001) greater than T3
      uptake, whereas the relative nuclear binding of the two tracers was comparable.
      The 15 min uptake of [125I]T3 was competitively inhibited by 10 microM unlabeled
      T3 (45-52%; P<0.001) or 3,3'- diiodothyronine (T2) (52%; P<0.001), and to a
      smaller extent by thyroxine (T(4)) (27%; 0.05<P<0.1). In contrast, 10 microM 3,5
      T2, Triac, or tetraiodothyroacetic acid (Tetrac) did not affect T3 uptake after
      15 min or after 24 h. Diiodothyropropionic acid (DITPA) (10 microM) reduced 15
      min T3 uptake by about 24% (P<0.05), but it had a greater effect after 4 h (56%;
      P<0.001). Exposure to 10 nM DITPA during culture reduced cellular T3 uptake, as
      did 10 nM T3, suggesting down-regulation of the plasma membrane T3 transporters.
      We conclude that i) Triac is taken up by cardiomyocytes; ii) 3,3'-T2 and, to a
      lesser extent, DITPA and T4 interfere with plasma membrane transport of T3,
      whereas 3,5-T2, Triac, or Tetrac do not; iii) the transport mechanism for Triac
      is probably different from that for T3.

PMID- 12010633
TI  - Cardiac contractile function is enhanced in isolated ventricular myocytes from
      growth hormone transgenic mice.
AB  - Growth hormone (GH) plays a key role in cardiac growth and function. However,
      excessive levels of GH often result in cardiac dysfunction, which is the major
      cause of death in acromegalic patients. Transgenic mice with GH over-expression
      serve as useful models for acromegaly and exhibit impaired cardiac functions
      using echocardiography, similar to those of human acromegaly. However, the
      mechanism underscoring the impaired ventricular function has not been well
      defined. This study was designed to evaluate the cardiac excitation-contraction
      coupling in GH over-expressing transgenic mice at the single ventricular myocyte
      level. Myocytes were isolated from GH and age-matched wild-type mouse hearts.
      Mechanical properties were evaluated using an IonOptix MyoCam system. The
      contractile properties analyzed included peak shortening (PS), time-to-peak
      shortening (TPS) and time-to-90% relengthening (TR(90)), and maximal velocities
      of shortening/relengthening (+/-dL/dt). Intracellular Ca2+ properties were
      evaluated by fura-2. GH transgenic mice exhibited significantly increased body
      weights and enlarged heart and myocyte size. Myocytes from GH transgenic mice
      displayed significantly enhanced PS and+/-dL/dt associated with similar TPS and
      TR(90) compared with the wild-type littermates. Myocytes from GH transgenic mice
      displayed a similar resting intracellular Ca2+ level and Ca2+ removal rate but
      exhibited an elevated peak intracellular Ca2+ level compared with the wild-type
      group. Myocytes from both groups were equally responsive to increases in
      extracellular Ca2+ concentration and stimulating frequency. These results suggest
      that GH over-expression is associated with enhanced contractile function in
      isolated myocytes and that the impaired cardiac function observed in whole hearts
      may not be due to defects at the myocyte level.

PMID- 12010634
TI  - Adenovirus-mediated gene transfer in the ovine pituitary gland is associated with
      hypophysitis.
AB  - Gene therapy for pituitary disease requires evaluation for safety as well as
      efficacy. We have reported results of adenovirus-mediated gene transfer using the
      sheep as a large animal model that allows longitudinal evaluation of hormone
      secretion and have confirmed high levels of transgene expression up to 7 days
      after direct stereotaxic injection into the pituitary gland. Here we report the
      results of detailed histological examination of the pituitary glands from animals
      injected with two recombinant adenoviruses expressing the beta-galactosidase
      marker gene, or with saline vehicle to control for the potential tissue
      disruptive effect of the injection volume itself. Pituitaries injected with
      saline showed no evidence of inflammatory response apart from occasional minor
      foci of apoptosis. In all other respects they were indistinguishable from normal
      uninjected control pituitary glands. Glands injected with recombinant
      adenoviruses containing either the hCMV-beta-gal or the hPRL-beta-gal transgene,
      on the other hand, displayed variable degrees of inflammatory response, with
      periglandular fibrosis, lymphocytic infiltrate and venulitis in almost all cases.
      Focal necrosis and/or apoptosis was noted in six of nine cases. In summary, we
      have found evidence of severe inflammatory reaction within the first seven days
      of adenovirus injection, amounting to significant hypophysitis. The histological
      extent of this reaction has not previously been recognised by studies of the
      efficacy of gene transfer in rodents, and was underestimated by
      immunocytochemical studies of hormone and transgene expression. The findings
      emphasise the need for careful evaluation of the safety of endocrine gene
      therapy, and for caution with the dose of vector used.

PMID- 12010635
TI  - gamma-Linoleic acid and ascorbic acid ameliorate the effects of experimental
      diabetes on electrolyte and bone homeostasis in pregnant rats.
AB  - Experimental diabetes in rats is associated with excessive electrolyte loss in
      the urine, which is further accentuated by pregnancy, particularly of Ca.
      Supplementation with essential fatty acids and antioxidants has proven beneficial
      in treating several types of complications, including nephropathy. The present
      study investigated the effect of gamma-linoleic acid (GLA; 500 mg/kg per day;
      group DG) and ascorbate (290 mg/kg per day; group DA), alone and in combination
      (group DGA), as well as ascorbyl-GLA (790 mg/kg per day; group DASG), on urinary
      electrolyte output and skeletal composition in pregnant streptozotocin-diabetic
      rats. Urine was collected in metabolism cages before and throughout pregnancy.
      Diabetic rats (DP) increased their urine volume as compared with control (CP)
      throughout the experiment, reaching an output of more than 13 times that of the
      control group by the end of pregnancy (CP 24+/-4, DP 316+/-21, DG 223+/-21, DA
      221+/-14, DASG 163+/-17, DGA 220+/-19 ml urine/24 h). Concomitant with increased
      urine volume was a reduction of urinary Na (CP 47+/-14, DP 22+/-5 mmol/l), K (CP
      210+/-34, DP 31+/-1 mmol/l) and Mg (CP 14+/-1, DP 3.8+/-0.2 mmol/l)
      concentration, but not of Ca concentration (CP 5.4+/-1.5, DP 6.3+/-0.6 mmol/l),
      and hence total Ca loss was relatively most severe. All the treatments reduced
      urine volume with no effects on electrolyte concentration as compared with DP,
      with no significant difference between the treatments. A reduced bone size and
      bone Ca content was partially ameliorated by the diet supplementation. We have
      concluded that GLA and ascorbate, alone or in combination, prevent urinary
      electrolyte loss in pregnant rats and do so by reducing urine production.

PMID- 12010636
TI  - Expression patterns of endothelial and inducible nitric oxide synthase isoforms
      in corpora lutea of pseudopregnant rabbits at different luteal stages.
AB  - Total activity of nitric oxide (NO) synthase (NOS) and expression of both
      endothelial (eNOS) and inducible (iNOS) isoforms were examined in corpora lutea
      (CL) of rabbits across pseudopregnancy by quantitative RT-PCR analysis, Western
      blot and immunohistochemistry. CL were collected at early- (day 4), mid- (day 9)
      and late- (day 13) luteal phases of pseudopregnancy. The PCR product of rabbit
      luteal eNOS was cloned and its direct sequence exhibited 90% homology with those
      of other species. The steady-state mRNA levels encoding eNOS remained fairly
      constant throughout both early- and mid-luteal stages of pseudopregnancy but
      dropped almost to half (P</=0.05) by day 13. By contrast, luteal eNOS proteins
      increased 2-fold (P</=0.05) from the early- to late-luteal phase. Independently
      of CL age, iNOS mRNA was very poorly expressed while protein levels gradually
      declined from the early- to late-luteal stage. Intense eNOS-like immunoreactivity
      was detected in large luteal cells, while iNOS staining was targeted to a few,
      isolated cells, probably macrophages. Basal NOS activity was greater in day 4 CL
      than in both day 9 and day 13 CL. These data are the first to characterize in
      rabbit CL the temporal expression patterns of NOS isoforms across different
      luteal stages of pseudopregnancy and, collectively, suggest the existence of an
      expressional control for this constitutive isoform, which might have a
      physiological role in regulating CL function during development.

PMID- 12010637
TI  - Delayed first cycle in intrauterine growth-retarded and postnatally
      undernourished female rats: follicular growth and ovulation after stimulation
      with pregnant mare serum gonadotropin at first cycle.
AB  - In the present study we examined the consequences of intrauterine growth
      retardation and postnatal food restriction on the maturational process of sexual
      development by studying onset of first cycle. In addition, we investigated the
      effect of pregnant mare serum gonadotropin (PMSG) on ovarian growth and ovulation
      in intrauterine growth-retarded (IUGR) and postnatally food-restricted (PFR)
      rats. Intrauterine growth retardation was induced by uterine artery ligation on
      day 17 of gestation and food restriction was achieved by enlarging the litter to
      20 pups per mother from day 2 after birth until weaning (day 24). In control
      rats, vaginal opening and the first cycle took place on the same day. In IUGR
      rats, uncoupling occurred between vaginal opening and the first cycle. Vaginal
      opening was delayed (P<0.05) and the first cycle was even further delayed
      (P<0.01) compared with controls. Body weight in IUGR rats was lower (P<0.05) at
      vaginal opening, but at first cycle and after stimulation with 50 IU PMSG in the
      first cycle it was similar to that in controls. In the ovaries of IUGR rats, the
      numbers of primordial (P<0.05), growing (P<0.01) and antral follicles (P<0.01),
      and the total number of follicles (P<0.01) were lower than in controls after
      stimulation with 50 IU PMSG at first cycle. The number of corpora lutea in the
      ovaries of the IUGR rats and the controls was similar and reflected
      superovulation. In the PFR rats, vaginal opening occurred at the same time as in
      control rats, but at a lower body weight (P<0.01). First cycle was much delayed
      (P<0.01), by which time body weight was greater (P<0.01) than that of controls at
      first cycle. On the basis of the differences in weight and age between PFR rats
      and controls at first cycle, we performed two studies. In study A, ovaries were
      analysed histologically 42 h after stimulation with PMSG at first cycle of
      control rats and age-matched PFR rats. In study B, the ovaries of PFR rats at
      first cycle and age-matched control rats were examined 42 h after PMSG
      stimulation. In the ovaries of the PFR rats in study A, a greater total number of
      follicles (P<0.05) was observed, represented by a greater number of primordial
      follicles (P<0.01) and a lower number of antral follicles (P<0.05), including
      corpora lutea. The number of corpora lutea in the ovaries of the PFR rats was
      significantly lower than that in controls (P<0.01). The total number of follicles
      in the ovaries of the PFR rats of study B did not differ from the age-matched
      controls after PMSG stimulation at first cycle, and neither did the number of the
      follicles in the different classes. We conclude that, in IUGR rats at first
      cycle, PMSG can induce multiple follicular growth and development followed by
      superovulation comparable to that in controls, despite a decreased total number
      of follicles in the ovaries. However, in PFR rats of the same age, the ovary is
      not capable of responding adequately to PMSG, despite a greater total number of
      follicles. Stimulation with PMSG at first cycle resulted in follicular growth and
      superovulation comparable to those in age-matched controls. Undernutrition in
      different critical time periods around birth in the rat leads to ovarian
      development in such a way that, in both groups, an increased risk of reduced
      reproductive capacity can be expected.

PMID- 12010638
TI  - Postnatal hypoxemia increases angiotensin II sensitivity and up-regulates AT1a
      angiotensin receptors in rat carotid body chemoreceptors.
AB  - In the present study, the effects of postnatal hypoxemia on the AT1 angiotensin
      receptor-mediated activities in the rat carotid body were studied. Angiotensin II
      (Ang II) concentration-dependently increased the chemoreceptor afferent activity
      in the isolated carotid body. Single- or pauci-fiber recording of the sinus nerve
      revealed that the afferent response to Ang II was enhanced in the postnatally
      hypoxic carotid body. To determine whether the increased sensitivity to Ang II is
      mediated by changes in the functional expression of Ang II receptors in the
      carotid body chemoreceptors, cytosolic calcium ([Ca2+]i) was measured by
      spectrofluorimetry in fura-2 acetoxymethyl ester-loaded type I cells dissociated
      from carotid bodies. Ang II (25-100 nM) concentration-dependently increased
      [Ca2+]i in the type I cells. The proportion of clusters of type I cells
      responsive to Ang II was higher in the postnatally hypoxic group than in the
      normoxic control (89 vs 66%). In addition, the peak [Ca2+]i response to Ang II
      was enhanced 2- to 3-fold in the postnatally hypoxic group. The [Ca2+]i response
      to Ang II was abolished by pretreatment with losartan (1 microM), an AT1 receptor
      antagonist, but not by PD-123177 (1 microM), an AT(2) antagonist. Double-labeling
      immunohistochemistry confirmed that an enhanced immunoreactivity for AT1 receptor
      was co-localized to the lobules of type I cells in the hypoxic group. In
      addition, RT-PCR analysis of subtypes of AT1 receptors showed an up-regulation of
      AT1a but a down-regulation of AT1b receptors, indicating a differential
      regulation of the expression of AT1 receptor subtypes by postnatal hypoxia in the
      carotid body. These data suggest that postnatal hypoxemia is associated with an
      increased sensitivity of peripheral chemoreceptors in response to Ang II and an
      up-regulation of AT1a receptor-mediated [Ca2+]i activity of the chemoreceptors.
      This modulation may be important for adaptation of carotid body functions in the
      hypoxic ventilatory response and in electrolyte and water homeostasis during
      perinatal and postnatal hypoxia.

PMID- 12010639
TI  - Angiotensin II stimulation of Na+/K+ATPase activity and cell growth by calcium
      independent pathway in MCF-7 breast cancer cells.
AB  - Here we demonstrated, by RT-PCR analysis, the expression of both angiotensin II
      (Ang II) receptor subtypes, AT1 and AT2, in a breast cancer epithelial cell line,
      MCF-7. Ang II was not able to affect the intracellular Ca2+ concentration in Fura
      2 loaded cells suggesting that AT1-mediated phospholipid hydrolysis is not
      involved in its intracellular transduction pathway. Ang II modulated the activity
      of the Na+/K+ATPase in a dose- and time-dependent manner and was mitogenic, with
      a dose-dependent (1-1000 nM) proliferative effect and a maximal response at 100
      nM. Both Na+/K+ATPase activation and stimulation of proliferation were mediated
      by binding of Ang II to AT1, as the effects were completely blocked by DuP 753, a
      specific AT1 antagonist. CGP 42112, an AT2 antagonist, did not affect Ang II
      actions. The main conclusion of this study is that Ang II exerts its effects on
      cell proliferation and Na+/K+ATPase in breast cancer epithelial cells, MCF-7, via
      AT1 activation independently of the Ca(2+) signalling mechanism.

PMID- 12010640
TI  - Muscarinic acetylcholine receptor activation induces Ca2+ mobilization and Na+/K+
      ATPase activity inhibition in eel enterocytes.
AB  - The effect of carbachol (Cch) on intracellular calcium concentration ([Ca2+]i) in
      eel enterocytes was examined using the fluorescent Ca2+ indicator fura-2. Cch
      caused a biphasic increase in [Ca2+]i, with an initial spike followed by a
      progressively decreasing level (over 6 min) to the initial, pre-stimulated,
      level. The effect of Cch was dose-dependent with a 7.5-fold increase in [Ca2+]i
      over basal level induced by the maximal dose of Cch (100 microM). In Ca2+
      free/EGTA buffer the effect of Cch was less pronounced and the [Ca2+]i returned
      rapidly to basal levels. The increment of [Ca2+]i was dose-dependently attenuated
      in cells pre-treated with U73122, a specific inhibitor of phospholipase C,
      suggesting that the Cch-stimulated increment of [Ca2+]i required inositol
      triphosphate formation. In the presence of extracellular Ca2+, thapsigargin (TG),
      a specific microsomal Ca2+-ATPase inhibitor, caused a sustained rise in [Ca2+]i
      whereas in Ca2+-free medium the increase in [Ca2+]i was transient; in both cases,
      subsequent addition of Cch was without effect. When 2 mM CaCl2 were added to the
      cells stimulated with TG or with Cch in Ca2+-free medium, a rapid increase in
      [Ca2+]i was detected, corresponding to the capacitative Ca2+ entry. Thus, both TG
      and Cch depleted intracellular Ca2+ stores and stimulated influx of extracellular
      Ca2+ consistent with capacitative Ca2+ entry. K+ depolarization obtained with
      increasing concentrations of KCl in the extracellular medium induced a dose
      related increase in [Ca2+]i which was blocked by 2 microM nifedipine, a non
      specific L-type Ca2+ channel blocker. Nifedipine also changed significantly the
      height of the Ca2+ transient, and the rate of decrement to the pre-stimulated
      [Ca2+]i level, indicating that Ca2+ entry into enterocytes also occurs through an
      L-type voltage-dependent calcium channel pathway. We also show that isolated
      enterocytes stimulated with increasing Cch concentrations (0.1-1000 microM)
      showed a dose-dependent inhibition of the Na+/K+-ATPase activity. The threshold
      decrease was at 1 microM Cch; it reached a maximum at 100 microM (50.5%
      inhibition) and did not decrease further with the use of higher dose. The effect
      of Cch on Na+/K+-ATPase activity was dependent on both protein kinase C (PKC) and
      protein phosphatase calcineurin activation since the PKC inhibitor calphostin C
      abolished Cch effects, while the calcineurin inhibitor FK506 augmented Cch
      effect. Collectively, these data establish a functional pathway by which Cch can
      modulate the activity of the Na+/K+-ATPase through a PKC-dependent (calphostin C
      sensitive) pathway and a calcineurin-dependent (FK506-sensitive) pathway.

PMID- 12010641
TI  - Regulation of lactate production and glucose transport as well as of glucose
      transporter 1 and lactate dehydrogenase A mRNA levels by basic fibroblast growth
      factor in rat Sertoli cells.
AB  - By using cultured rat Sertoli cells as a model, both the action of basic
      fibroblast growth factor (bFGF) on lactate production and the site of this action
      were studied. bFGF stimulated Sertoli cell lactate production in a dose-dependent
      manner (basal: 7.3+/-0.5; 0.1 ng/ml bFGF: 7.5+/-0.5; 1 ng/ml bFGF: 7.5+/-0.6; 10
      ng/ml bFGF: 10.3+/-1.0; 30 ng/ml bFGF: 15.2+/-1.5; 50 ng/ml bFGF: 15.4+/-1.6
      microg/microg DNA). Two major sites for the action of this growth factor were
      identified. First, bFGF was shown to exert short- and long-term stimulatory
      effects on glucose transport (basal: 1170+/-102; 30 ng/ml bFGF for 120 min:
      1718+/-152 and basal: 718+/-64; 30 ng/ml bFGF for 48 h: 1069+/-69 d.p.m./microg
      DNA respectively). Short-term bFGF stimulation of glucose transport was not
      inhibited by the protein synthesis inhibitor cycloheximide. These results
      indicate that short-term bFGF stimulation of glucose uptake does not involve an
      increase in the number of glucose transporters. On the other hand, stimulation
      with bFGF for periods of time longer than 12 h increased glucose transporter 1
      (GLUT1) mRNA levels. These increased mRNA levels were probably ultimately
      responsible for the increments in glucose uptake that are observed in long-term
      treated cultures. Secondly, bFGF increased lactate dehydrogenase (LDH) activity
      (basal: 31.0+/-1.4; 30 ng/ml bFGF: 45.7+/- 2.4 mIU/microg DNA). The principal
      subunit component of those LDH isozymes that favors the transformation of
      pyruvate to lactate is subunit A. bFGF increased LDH A mRNA levels in a dose- and
      time-dependent manner. In summary, the results presented herein show that glucose
      transport, LDH activity and GLUT1 and LDH A mRNA levels are regulated by bFGF to
      achieve an increase in lactate production. These observed regulatory actions
      provide unequivocal evidence of the participation of bFGF in Sertoli cell lactate
      production which may be related to normal germ cell development.

PMID- 12010642
TI  - TGFbeta1 effects on functional activity of porcine thyroid cells cultured in
      suspension.
AB  - Thyrotropin (TSH) and transforming growth factor beta 1 (TGFbeta1) have major
      roles in the regulation of folliculogenesis and differentiation in thyroid cells.
      Isolated porcine thyroid cells cultured in the presence of TSH on a plastic
      surface recover a follicular architecture and exhibit normal functional
      properties. The addition of TGFbeta1 to the culture medium induces important
      morphological changes and extracellular matrix remodelling. Similarly, thyroid
      cells lose their ability to organify iodine and their responsiveness to adenylate
      cyclase. The aim of this study was to analyse the influence of TGFbeta1 on the
      functional activity of thyrocytes in suspension culture, independent of follicle
      disruption. In this system, we demonstrate that TGFbeta1 inhibits expression of
      thyroperoxidase, NADPH oxidase activity, iodine uptake and, consequently, iodine
      organification. Moreover, TGFbeta1 decreases basal and TSH-stimulated cAMP
      production and TSH receptor expression. Taken together, these data converge to
      demonstrate an essential role of TGFbeta1 in the regulation of the thyroid cell
      function.

PMID- 12010643
TI  - Arthritis-induced increase in serum levels of IGF-binding protein-3 in rats is
      secondary to the decrease in its proteolytic activity.
AB  - Adjuvant-induced arthritis is a chronic inflammatory illness that induces a
      catabolic state, with a decrease in pituitary GH and hepatic IGF-I synthesis. We
      have previously observed an increase in serum IGF-binding protein-3 (IGFBP-3) in
      arthritic rats, and found that GH administration prevents the increase in
      circulating IGFBP-3 in arthritic rats. The aim of this work was therefore to
      study IGFBP-3 synthesis in the liver as well as its proteolysis in serum as the
      two possible causes of the increased circulating IGFBP-3 in arthritic rats. The
      effect of recombinant human GH (rhGH) administration was also analysed. Adult
      male Wistar rats were injected with complete Freund's adjuvant or vehicle, and 14
      days later they were injected s.c. daily until day 22 after adjuvant injection
      with rhGH (3 IU/kg) or saline. Three hours after the last GH injection, all rats
      were killed by decapitation. Arthritis increased serum IGFBP-3 levels (P<0.01).
      The increase in serum IGFBP-3 levels in arthritic rats seems to be due to
      decreased proteolysis (P<0.01) rather than to an increased synthesis, since liver
      IGFBP-3 mRNA content was not modified by arthritis. GH administration to control
      rats resulted in an increase in both hepatic IGFBP-3 mRNA content and in serum
      IGFBP-3 levels in spite of the increase in IGFBP-3 proteolysis in serum. In
      arthritic rats, GH treatment did not modify liver IGFBP-3 synthesis, but it
      increased serum proteolysis of IGFBP-3, leading to a serum concentration of IGFBP
      3 similar to that of control rats. Furthermore, there was a negative correlation
      between circulating IGFBP-3 and its proteolytic activity in the serum of adjuvant
      induced arthritic rats. These data suggest that in chronic arthritis the increase
      in IGFBP-3 serum concentration is secondary to a decrease in proteolytic
      activity, rather than to an increase in hepatic IGFBP-3 gene expression.

PMID- 12010644
TI  - Molecular cloning, identification and characterization of four distinct receptor
      subtypes for insulin and IGF-I in Japanese flounder, Paralichthys olivaceus.
AB  - Insulin receptor (IR) and IGF-I receptor (IGF-IR) are structurally and
      functionally related and belong to the tyrosine kinase receptor family. In
      teleosti such as salmonids and turbot, occurrence of multiple IR and IGF-IR
      members has been reported, but the structures of a complete set of both IR and
      IGF-IR members in a single teleost species have not yet been characterized. In
      this study, we cloned and analysed four distinct cDNA clones for IR and IGF-IR
      members from the liver and kidney of the Japanese flounder (Paralichthys
      olivaceus). Deduced amino acid sequence analyses and phylogenetic analysis have
      revealed that two of them (fIR-1 and fIR-2) belong to IR members and the other
      two (fIGF-IR-1 and fIGF-IR-2) are IGF-IRs. fIR-1 and fIR-2 comprised 1369 and
      1368 amino acid residues respectively, and fIGF-IR-1 and fIGF-IR-2 comprised 1412
      and 1418 residues respectively. All the receptor proteins contained cysteine-rich
      domains in their alpha-subunits, and conserved each transmembrane and tyrosine
      kinase domains in their beta-subunits. The amino acid sequences of fIRs and fIGF
      IRs showed more than 90% sequence identity with turbot IR and IGF-IR
      respectively. When compared with their mammalian homologues, fIGF-IR-1 and fIGF
      IR-2 proteins contained large insertions at their C-termini, as was observed in
      the corresponding region of turbot IGF-IR. Occurrence of multiple species of mRNA
      for each IR and IGF-IR was suggested by Northern blot analyses. A ribonuclease
      protection assay revealed diverse expressions of four receptor mRNAs in a wide
      range of tissues including heart, liver, ovary, testis, brain, gill arch, kidney,
      skeletal muscle, intestine, stomach, spleen and eye of the flounder.

PMID- 12010645
TI  - Calcium balance in sea bream (Sparus aurata): the effect of oestradiol-17beta.
AB  - In all teleost fishes vitellogenesis is triggered and maintained by oestradiol
      17beta (E2) and is accompanied by an increase of blood plasma calcium and
      phosphate. The action of this hormone on calcium metabolism was investigated by
      treating fast-growing immature juvenile sea bream (Sparus aurata) with coconut
      butter implants alone (control) or implants containing 10 microg/g E2. Treatment
      with E2 induced the production of circulating vitellogenin, a 2.5-fold increase
      in plasma ionic Ca2+ and a 10-fold increase in plasma total calcium, largely
      bound to protein. In contrast to freshwater species, which obtain most of their
      calcium from the environment directly through the gills, the intestinal component
      of calcium uptake of the salt water-living sea bream represented up to 60-70% of
      the total uptake. The whole body calcium uptake, expressed as the sum of calcium
      obtained via intestinal and extra-intestinal (likely branchial) routes increased
      significantly in response to E2. Combined influx and unchanged efflux rates
      resulted in a significant 31% increase in net calcium uptake. There was no
      evidence for an effect of E2 on the calcium and phosphate content of the scales
      or the tartrate-resistant acid phosphatase activity (an index for bone/scale
      osteoclast activity). While most freshwater fish appear to rely on internal
      stores of calcium, i.e. bone and/or scales to increase calcium availability, the
      marine sea bream accommodates calcium-transporting mechanisms to obtain calcium
      from the environment and preserve internal stores. These observations suggest
      that a fundamental difference may exist in the E2-dependent calcium regulation
      between freshwater and marine teleosts.

PMID- 12010646
TI  - Direct effects of ciliary neurotrophic factor on brown adipocytes: evidence for a
      role in peripheral regulation of energy homeostasis.
AB  - Ciliary neurotrophic factor (CNTF) plays an important role in regulating neuronal
      growth. Recently, central anorexigenic effects of this cytokine have been
      characterized. However, peripheral effects on tissues that actively contribute to
      the regulation of energy homeostasis have not been described. Here, we report
      direct potent and selective effects of CNTF on growth factor and metabolic
      signalling intermediates in mouse brown adipocytes. CNTF stimulates STAT3, MAP
      kinase, Akt, and p70 S6 kinase. We find that, next to mediating Akt and p70 S6
      kinase activation, both phosphatidylinositol 3-kinase and protein kinase C are
      separately acting, main intermediates for inducing mitogen-activated protein
      (MAP) kinase activation. On a functional level, CNTF enhances beta3-adrenergic
      induction of uncoupling protein-1. Thus, these results demonstrate direct effects
      of CNTF on adipose tissue signalling and metabolism and suggest a novel role for
      this cytokine in the peripheral regulation of energy homeostasis.

PMID- 12010647
TI  - Identification of urocortin mRNA and peptide in the human endometrium.
AB  - Urocortin is a 40-amino acid peptide belonging to the corticotropin-releasing
      factor (CRF) family. In human reproductive tissues, urocortin expression has been
      previously demonstrated in the ovary, in the placenta and fetal membranes and in
      pregnant uterine tissues, while no data are available on the expression of the
      peptide in the nonpregnant uterus. In this study, urocortin expression was
      evaluated by both immunohistochemistry and reverse transcription-polymerase chain
      reaction, in human uterine tissues and cells at different phases of the menstrual
      cycle. Urocortin was immunolocalized in endometrial epithelial and stromal cells,
      as well as in the myometrium, and in vascular smooth muscle cells. No differences
      between proliferative and secretory phase were observed. These results were
      confirmed by reverse transcription-polymerase chain reaction analysis of isolated
      endometrial epithelial and stromal cells, and myometrial specimens. These
      findings open new questions on the roles played by urocortin in the human uterus.

PMID- 12010648
TI  - Calculation is unsuitable for determination of O2-consumption (VO2) in case of O2
      supply-dependency.
AB  - BACKGROUND: When O2-delivery to tissues is critically reduced, O2-consumption
      becomes dependent on O2-delivery and starts to decline, which reflects tissue
      hypoxia. In order to timely detect tissue hypoxia prior to organ damage, O2
      consumption may be calculated or measured from respiratory gases. We have
      assessed reproducibility of calculated and measured O2-consumption-data and their
      agreement during O2-supply-dependency. METHOD: Data of 31 anesthetized,
      ventilated pigs were analysed retrospectively. Animals had undergone either
      controlled hemorrhage ("shock") or isovolemic exchange of blood with colloids
      (extreme hemodilution, "HD") until O2-consumption had become dependent on O2
      delivery. O2-consumption was calculated from the Fick equation and measured
      simultaneously with a DELTATRAC II metabolic monitor. Repeatability was
      determined for (1) calculated and (2) for measured.VO2 -values and (3) for input
      variables of the Fick equation (i.e. cardiac index (CI) and arteriovenous O2
      content difference (CaO2-CvO2)). Bias between calculated and measured data and
      precision of calculation were assessed from paired O2-consumption-values obtained
      before and after induction of O2-supply-dependency via hemorrhage or extreme
      hemodilution. RESULTS: Repeatability of the reversed Fick method was inferior to
      repeatability of measurement (27 vs 15%) due to error propagation from CI and
      (CaO2-CvO2). Between-method-bias at baseline ("BL") was 3%, and changed in case
      of O2-supply-dependency (shock -15%; HD -31%, both p<0.05 vs BL), precision of
      the reversed Fick method deteriorated (BL 32%; shock 60%; HD 60%) due to
      variability of CI (CV: 16%; shock 27%; HD 41%). CONCLUSION: In anesthetized pigs
      calculated and measured O2-consumption values are in agreement, while in presence
      of O2-supply-dependency the reversed Fick method (1) grossly underestimates true
      O2-consumption and (2) precision deteriorates not allowing to verify or reject
      the presence of tissue hypoxia.

PMID- 12010649
TI  - Triple antiviral re-therapy for chronic hepatitis C with interferon-alpha,
      ribavirin and amantadine in nonresponders to interferon-alpha and ribavirin.
AB  - BACKGROUND: Therapy options for patients with chronic hepatitis C who failed
      prior treatment are needed. In recent studies triple antiviral therapy with
      Interferon-alpha, ribavirin, and amantadine seemed to increase sustained
      virological response rates in this group. METHOD: To evaluate efficacy, side
      effects and safety of a triple re-therapy in an open labeled prospective study,
      we compared 23 nonresponders to interferon monotherapy (9 nonresponders, 3
      relapsers, 11 with breakthrough) with 23 nonresponders to standard combination
      therapy (interferon plus ribavirin) (16 nonresponders, 7 breakthroughs). All
      outpatients enrolled for re-therapy received interferon-alpha 2a (6 mega units
      [MU] three times in week), ribavirin (1000-1200 mg daily in divided doses) and
      amantadine (200 mg daily) for six months. In case of virological re-therapy
      response (negative qualitative HCV RNA) study medication was continued with
      interferon monotherapy for another six months. RESULTS: Sustained virological
      response was achieved in 16 (35%) out of 46 prior therapy nonresponders. Response
      rates were dependent on pretreatment outcome. In the standard combination therapy
      group only 1 (6%) primary nonresponder achieved sustained response, but none of
      the 9 monotherapy nonresponders did. After primary breakthrough sustained
      response was seen in 8 of 11 (73%) patients in the interferon monotherapy and in
      5 of 7 (71%) in the combination therapy group. Of 3 monotherapy relapsers 2 (66%)
      did also clear the virus sustained. Safety profile under triple therapy was
      similar to the previous therapy. Compliance was higher and side effects lower in
      those patients already experienced in combination therapy. CONCLUSION: In
      patients with a breakthrough or relapse after interferon monotherapy or standard
      combination therapy with interferon and ribavirin a re-therapy with a triple
      combination of interferon, ribavirin, and amantadine results in a high rate of
      sustained virological response.

PMID- 12010650
TI  - In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure
      to aqueous mistletoe extracts: a randomised double-blinded placebo controlled
      phase I study in healthy individuals.
AB  - BACKGROUND: Several studies have been performed in tumour patients to analyse the
      immunological response to mistletoe extracts. Considering the fact that these
      extracts are given subcutaneously in most instances, the kind of application
      resembles a typical immunization schedule. We therefore wanted to see how those
      extracts act on immunocompetent cells of healthy individuals hoping that this
      kind of provocation test may give new informations about a more specific
      application of these extracts in certain diseases. SUBJECTS/METHODS: 47 healthy
      individuals were exposed for twelve weeks either to Iscador Quercus special (IQ)
      known to be rich in mistletoe lectin (ML)-1 (n = 16), to Iscador Pini (IP) being
      poor in ML-1 but enriched in viscotoxins (n = 15), or to placebo (physiological
      saline) (n = 16) in a randomised, double-blinded placebo-controlled study.
      Humoral immunoreactivity was analysed by measuring antibodies towards the two
      compounds ML-1 and viscotoxin VA2 (VA2). Sera were collected in intervals of four
      weeks up to week 12 and again three months after last exposure. RESULTS: None of
      the subjects had antibodies to ML-1 or VA2 before exposure. In week 12, anti-ML-1
      antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6
      of the 15 probands exposed to IP. In contrast, anti-VA2 IgG-antibodies could be
      detected in all individuals of both groups. The antibodies were preferentially of
      the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced
      only in a few probands. Antibodies of the IgE-type occurred only in the IQ
      exposed individuals and were directed against ML-1 but not VA2. None of the
      probands receiving placebo developed antibodies to ML-1 or VA2. Severe side
      effects were not observed in any of the probands. CONCLUSIONS: These data
      obtained in healthy individuals clearly indicate that IQ and IP-extracts can
      induce antigen-specific humoral responses. They may, therefore, provide, a solid
      basic for the evaluation of the humoral immune response in disease states.

PMID- 12010651
TI  - Rapid identification of high-risk patients after minor head trauma (MHT) by
      assessment of S-100B: ascertainment of a cut-off level.
AB  - BACKGROUND: Elevated blood S-100B levels were described by several authors for
      reliable identification of patients with intracerebral complications after minor
      head trauma (MHT). Yet, test systems used so far require more than 3 hours
      processing period which is too long to enable immediate further diagnostic or
      therapeutic consequences. Therefore we validate a new rapid test version for S
      100B measurements and established an effective cut-off level to identify high
      risk patients. METHODS: 104 patients suffering from MHT were enrolled. After
      taking blood samples S-100B values were achieved by the long-term and rapid (40
      min processing time) test system, respectively, and compared using linear
      regression analysis. For determination of an effective cut-off level receiver
      operating characteristics curves were calculated in accordance with cranial
      computed tomography findings. RESULTS: S-100B concentrations correlated
      significantly using both test systems. A cut-off level of 0.18ng/ml was
      calculated in plasma samples. CONCLUSIONS: S-100B concentrations above the cut
      off level measured within 40 min after blood sampling allows safe identification
      and immediate treatment of intracerebral lesions (e.g. epidural and subdural
      hematoma, subarachnoid hemorrhage, diffuse brain edema etc.) in MHT patients.

PMID- 12010652
TI  - The tumour necrosis factor-alpha induced vascular permeability is associated with
      a reduction of VE-cadherin expression.
AB  - BACKGROUND: Vascular permeability is controlled by endothelial cell-to-cell
      junctions. Vascular endothelial (VE)-cadherin, the major component of adherence
      junctions (AJ) in the endothelium, is the target of the permeability-increasing
      agent tumour necrosis factor-a (TNF-alpha). We investigated whether TNF-alpha
      regulates the synthesis of VE-cadherin on the transcriptional level. MATERIALS
      AND METHODS: Human endothelial cells, isolated from aorta (aEC) and umbilical
      cord (HUVEC), were exposed to TNF-alpha (200 U/ml) for 6 h or 12 h, with and
      without subsequent incubation with TNF-alpha for 24 h. VE-cadherin mRNA was
      evaluated by semi-quantitative RT-PCR. The VE-Cadherin protein expression was
      analyzed by flow cytometry (FACS). RESULTS: The VE-cadherin amplification curve
      of TNF-alpha treated cells was shifted to the right compared to controls,
      indicating a lower mRNA amount. The number of cycles at which half-maximal
      amplification (N50) was achieved, was lower for control aEC (30.7) than for TNF
      alpha treated aEC (33.0). The N50 of HUVEC treated with TNF-alpha for 12 h and 12
      h + 24 h medium (N50 = 32.1), was higher compared to controls (N50 = 29.7) and
      cells treated with TNF-alpha for 6 h (N50 = 30.8). As determined by FACS
      analysis, incubation with TNF-alpha caused a small decrease of VE-cadherin
      protein expression from 7.44 to 6.05 mean channel intensity. CONCLUSION: Our
      results indicate that TNF-alpha affects VE-cadherin gene expression on the
      transcriptional level, inducing a downregulation of the VE-cadherin expression.

PMID- 12010653
TI  - Aspergillus antigen and PCR assays in bone marrow transplanted children.
AB  - Screening for Aspergillus antigen and DNA has been introduced for the early
      diagnosis of invasive aspergillosis (IA) in adults, but data in children at risk
      are scarce. Seventeen 1-108 month-old children were screened for Aspergillus
      antigenaemia by a commercial assay before and after bone marrow transplantation
      (BMT). Seventy-one serum samples were examined retrospectively by a novel nested
      PCR assay. Results of both assays were correlated with clinical, radiological and
      microbiological findings used for the definition of invasive aspergillosis by the
      European Organisation for Research and Treatment of Cancer (EORTC). Three cases
      of probable or possible IA were defined, and in 14 children invasive
      aspergillosis was ruled out. In 10 children, Aspergillus antigen was detected in
      at least two consecutive serum samples, a microbiological EORTC criteria of IA.
      Specific DNA was detected in 8 antigen-positive and 2 antigen-negative sera. A
      positive predictive value of 20% was calculated for both assays. Hence, a high
      rate of positive results of antigen Elisa and PCR assays in BMT children are due
      to transient antigenaemia and fungaemia without clinical relevance. According to
      our data, prospective studies in well defined pediatric patients are urgently
      needed to determine the value of serial Aspergillus PCR assays for the early
      diagnosis of invasive aspergillosis in children at risk.

PMID- 12010654
TI  - Are we sure we all do the same things? Results from a GITMO survey on basic
      practices in allogeneic bone marrow transplantation.

PMID- 12010655
TI  - Clinical usefulness of arsenic trioxide in the treatment of acute promyelocytic
      leukemia.

PMID- 12010656
TI  - Cell division cycle manipulation and cancer treatment: a solid promise or just a
      dream?

PMID- 12010657
TI  - Association of specific cytogenetic aberrations with mdr1 gene expression in
      adult myeloid leukemia and its implication in treatment outcome.
AB  - BACKGROUND AND OBJECTIVES: Cytogenetics and mdr1 expression are established
      prognostic factors for treatment outcome in adult acute myeloid leukemia (AML).
      The association, however, between specific cytogenetic aberrations and mdr1
      expression has not yet been examined in a large cohort of patients. DESIGN AND
      METHODS: We therefore looked for mdr1 gene expression at diagnosis within
      specific cytogenetic aberrations in 331 previously untreated adult patients with
      de novo or secondary AML (not including t(15;17)) entered into the German SHG
      AML96 treatment trial. RESULTS: The proportion of mdr1 positive blast probes was
      significantly higher in patients with aberrant karyotypes than in those with
      normal karyotypes (39% vs. 15%; p<0.001). Looking at specific cytogenetic
      aberrations significantly more mdr1 positive AML patients were found within
      t(8;21), +8, +21, del(7q), del(5q), -7, abn(3q) and multiple aberrations. In
      contrast, no patient with inv(16) was positive for mdr1. Only 26% of mdr1
      positive patients with aberrant karyotypes achieved complete remission (CR)
      whereas 54% of the mdr1 negative counterparts did so (p=0.002). Furthermore,
      within abn(11q), +21, +22, -5 or abn(3q) no mdr1 positive patient reached CR,
      whereas the mdr1 negative counterparts had CR rates comparable to the CR rate of
      patients with a normal karyotype. This was most impressive in mdr1 negative
      patients with multiple aberrations achieving a CR rate of 63% (p=0.019). In the
      multivariate analysis age, disease status and mdr1 expression were the strongest
      independent predictors for induction treatment failure. INTERPRETATION AND
      CONCLUSIONS: The correlation described here between mdr1 gene expression and some
      cytogenetic aberrations might explain the prognostic divergence of such
      cytogenetic aberrations in different AML treatment trials due to the amount of
      mdr-drugs used within the protocols.

PMID- 12010658
TI  - Angiogenic activity of rat mast cells in the chick embryo chorioallantoic
      membrane is down-regulated by treatment with recombinant human alpha-2a
      interferon and partly mediated by fibroblast growth factor-2.
AB  - BACKGROUND AND OBJECTIVES: Many data suggest that the density of mast cells (MC)
      is strongly correlated with the extent of both normal and pathologic
      angiogenesis, such as the vessel formation that occurs in chronic inflammatory
      diseases and tumors. We have previously demonstrated that isolated MC and their
      secretory granules, but not degranulated MC, induce an angiogenic response in the
      chick embryo chorioallantoic membrane (CAM) assay. DESIGN AND METHODS: The aim of
      this study was to investigate whether pre-treatment of MC with an anti-angiogenic
      molecule, namely recombinant human interferon-alpha2a (rhIFN-alpha2a), reduced
      the angiogenic activity of their conditioned media (CM) in the CAM assay.
      RESULTS: Our data indicate that rhIFN-alpha2a at 500-1000 IU is able to reduce
      the angiogenic activity of CM significantly. When MC were treated with rhIFN
      alpha2a at 25-250 IU they retained their angiogenic activity. Addition of anti
      fibroblast growth factor-2 (FGF-2) antibodies (but not anti-vascular endothelial
      growth factor) substantially reduced the angiogenic activity of CM treated with
      sub-optimal concentrations of rhIFN-alpha2a. INTERPRETATION AND CONCLUSIONS: FGF
      2 may be the main angiogenic factor secreted by MC and higher concentrations of
      rhIFN-alpha2a possibly inhibit angiogenesis by blocking the actions of FGF-2
      produced by MC. Finally, the morphologic features of MC treated with rhIFN
      alpha2a, characterized by an atypical secretory pathway, are compatible with a
      slow release of the angiogenic cytokines stored in MC granules.

PMID- 12010659
TI  - High prevalence of a screening-detected, HFE-unrelated, mild idiopathic iron
      overload in Northern Italy.
AB  - BACKGROUND AND OBJECTIVES: In Italy, typical HFE mutations account for only 64%
      of the cases with overt hereditary hemochromatosis (HH), and a common HFE
      unrelated disease was hypothesized. DESIGN AND METHODS: One thousand and fifty
      potential blood donors were screened by iron tests, C282Y and H63D HFE mutation
      analysis in a region in North Italy. Subjects with repeated fasting transferrin
      saturation of 45% or more and no secondary iron overload were defined as probands
      with idiopathic iron overload. To assess the inheritance of iron overload,
      relatives of probands were screened. RESULTS: The overall frequency of probands
      with idiopathic iron overload was 3.43% (95% confidence interval, 2.32 to 4.52).
      Of these, 8.4% had genotypes associated with HH (compound heterozygous for
      H63D/C282Y or homozygous for H63D HFE mutations), and 91.6% had atypical
      genotypes: 47.2% were heterozygous for C282Y or H63D HFE mutations, and 44.4% had
      wild type/wild type genotype. A family history of iron overload was proven in
      33.3% of probands with atypical genotypes (1.04% of the overall population).
      Pedigree analysis excluded linkage of heterozygous HFE mutations with iron
      overload (cumulative lod score 2.41) and documented a recessive non-HLA-linked
      locus accounting for iron overload in wild type/wild type genotypes. None of the
      probands had clinical signs of iron accumulation; in males, serum ferritin
      positively correlated with age (r=0.63, p<0.01), and the regression model
      predicted a serum ferritin of 700 ng/mL at the age of 58. INTERPRETATION AND
      CONCLUSIONS: In Northern Italy an HFE-unrelated, mild idiopathic iron overload is
      highly prevalent. A recessive locus accounts for iron overload in at least 1.04%
      of the overall population.

PMID- 12010660
TI  - Patterns of iron distribution in liver cells in beta-thalassemia studied by X-ray
      microanalysis.
AB  - BACKGROUND AND OBJECTIVES: beta-thalassemia is an important public health problem
      in the countries bordering the Mediterranean sea. One of the major consequences
      of this disorder, primarily (due to an ineffective erythropoiesis) or secondarily
      to blood transfusions (which are necessary for the patient's survival), is iron
      storage. Applying X-ray microanalysis we wanted to demonstrate the different
      sites of iron storage in subcellular compartments (mitochondria, cytosol,
      nucleus, rough endoplasmic reticulum and lipid droplets) and whether there were
      any other trace elements stored in liver cell. DESIGN AND METHODS: X-ray
      microanalysis was performed (at 100 kV in the STEM mode of a Hitachi H7000) on
      thin sections from specimens of liver biopsies from 6 patients affected by b
      thalassemia, during follow-up after bone marrow transplantation. RESULTS: Spectra
      showed no correlation between iron peaks of lysosomes and hepatic iron
      concentration (HIC) or serum ferritin levels. Iron peaks were also detected in
      other subcellular compartments such as cisternae of rough endoplasmic reticulum,
      mitochondria and cytosol. No iron peaks were detected in lipid droplets and no
      significant iron peaks were found in the nuclei. Traces of copper were almost
      constantly found in lysosomes and cytosol. INTERPRETATION AND CONCLUSIONS: These
      results demonstrated iron storage within subcellular organelles other than
      lysosomes and highlighted a non-correlation between lysosomal iron peaks and HIC
      or serum ferritin levels. The presence of traces of copper in the lysosomes and
      in the cytosol may be correlated with the stronger hypothesis of links in the
      metabolism of the two elements (iron and copper), as ceruloplasmin is a
      ferroxidase copper-dependent protein. X-ray microanalysis may become a relevant
      tool in the localization of iron storage within hepatocytes in the evaluation of
      the effectiveness of bone marrow transplantation and iron chelation therapy. It
      also may provide some interesting information about iron metabolism in
      hepatocytes.

PMID- 12010662
TI  - Intracellular tumor necrosis factor production by T- and B-cells in B-cell
      chronic lymphocytic leukemia.
AB  - BACKGROUND AND OBJECTIVES: The pathogenesis of B-cell chronic lymphocytic
      leukemia (B-CLL) has been linked with the production and activity of certain
      growth factors. Tumor necrosis factor (TNF-alpha) is important for the growth and
      survival of B-CLL cells. TNF-alpha promotes the proliferation of the malignant
      cell clone and is believed to play a role in the progression of B-CLL. The aim of
      our study was to examine the level of production and intracellular expression of
      TNF-alpha by T- and B-cells in B-CLL in correlation with stage of disease and
      clinical parameters. DESIGN AND METHODS: Using a three-color flow cytometry
      technique we analyzed intracellular TNF-alpha expression by B-cells (CD19+) and
      by T-cell subsets (CD3+/CD4+ and CD3+/CD8+) in peripheral blood (PB) and bone
      marrow (BM) from 40 patients with B-CLL and 24 healthy controls. RESULTS: A
      higher number of TNF-a-positive B-cells were found in PB and BM in B-CLL patients
      than in normal controls. In BM this difference was statistically significant
      (p<0.007). Likewise, in PB and BM the percentage of T-cells expressing TNF-alpha
      was significantly higher in B-CLL patients than in normal controls (PB:
      p<0.00001; BM: p<0.007). CD3+/CD4+ cells from patients displayed a lower level of
      intracellular TNF-alpha expression than did CD3+/CD8+ cells (PB: p<0.0001; BM:
      p<0.04). The number of T-cells expressing TNF-alpha in B-CLL patients was higher
      in those with stages III-IV than in patients with early stage disease (PB:
      p<0.007; BM: p<0.01). Additionally, PB and BM T-cell subsets from patients in
      stages III-IV had a statistically significant higher level of cytoplasmic TNF-a
      expression than the corresponding cells from healthy controls (PB: p<0.02; BM:
      p<0.05). In PB the percentage of CD4+ and CD8+ T-cells expressing cytoplasmic TNF
      alpha positively correlated with the stage of disease, total tumor mass (TTM)
      score and lymphocytosis. In BM only the percentage of CD8 T-cells positively
      correlated with TTM score and lymphocytosis. The expression of TNF-alpha in
      leukemic B-cells did not correlate with any progression parameters of disease.
      INTERPRETATION AND CONCLUSIONS: The results obtained suggest that malignant B
      cells are exposed to large numbers of T-cells able to synthesize and secrete TNF
      alpha. Moreover, T-cells even though fewer than B-cells may be an important
      source of TNF-a in advanced stages of disease. This indicates that the TNF-alpha
      can be associated with progression of B-CLL and may be implicated in some side
      effects associated with this disease.

PMID- 12010661
TI  - Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Arsenic trioxide (ATO) has been reported to be a safe
      and effective treatment for relapsed acute promyelocytic leukemia (APL). The aim
      of this study was to evaluate the efficacy and toxicity as well as the
      eligibility to stem cell transplantation (SCT) in a series of 7 patients with
      relapsing APL, managed with ATO. DESIGN AND METHODS: Seven patients with
      relapsing APL while on maintenance treatment with all-trans-retinoic acid (ATRA)
      or who were ATRA refractory-received ATO at a dose of 10 mg daily by 2-hour
      intravenous infusion until complete remission (CR). After consolidation
      chemotherapy, patients were programmed to receive autologous or allogeneic stem
      cell transplantation (SCT) according to donor availability. The median age of the
      patients was 55 (21-71) years: 2 patients presented with concomitant
      extramedullary relapse. RESULTS: Six patients (86%) achieved CR after a median of
      35 ATO doses (20-49) with negligible toxicity; one patient died from pneumonia.
      After consolidation with a four-day course of cytarabine at 1 g/m2 and
      mitoxantrone 6 mg/m2, two patients underwent allogeneic SCT, two received
      PML/RARa negative autologous peripheral blood stem cells collected after
      consolidation plus granulocyte colony-stimulating factor, one failed mobilization
      and received a second consolidation course. One elderly patient refused further
      treatment and relapsed 6 months later. After a median follow-up of 15 months from
      CR2 achievement, 5 patients are alive in continuous CR. INTERPRETATION AND
      CONCLUSIONS: The high CR rate and the mild toxicity confirm that ATO represents a
      valid alternative to salvage chemotherapy for patients relapsing while on ATRA
      treatment or who are ATRA-refractory. Allogeneic or autologous SCT after ATO
      induced CR is feasible in the majority of patients.

PMID- 12010663
TI  - Downstaging Rai stage III B-chronic lymphocytic leukemia patients with the
      administration of recombinant human erythropoietin.
AB  - BACKGROUND AND OBJECTIVES: To investigate the effectiveness of recombinant human
      erythropoietin (r-HuEPO) on disease-related anemia in patients with B-chronic
      lymphocytic leukemia (B-CLL) and to explore whether improvement of anemia could
      delay the initiation of cytotoxic therapy. DESIGN AND METHODS: Twenty five B-CLL
      patients (12 males and 13 females; median age 70 years) with disease-related
      anemia were treated with r-HuEPO. Patients were either on no treatment or on a
      standard regimen, and had at least Rai stage III disease, with a hematocrit (Hct)
      <32%. Eleven were newly diagnosed, whereas 14 developed anemia during follow-up.
      Treatment induction lasted for a maximum of 3 months, during which patients were
      receiving 150 IU/kg of r-HuEPO s.c. t.i.w. with an escalation to 300 IU/kg t.i.w.
      if response was slow after one month. Responding patients were placed on
      maintenance r-HuEPO with 150 IU/kg s.c. once weekly, continuously. Complete
      response (CR) was defined as an increase of Hct to 38% or more and partial
      response (PR) as an increase of >6% from pretreatment level. RESULTS: CR was
      observed in 18/25 (72%) and PR in 2/25 (8%) of the patients. Six patients were
      downstaged to stage Rai 0, 9 to Rai I and 4 to Rai II. Response was sustained
      with maintenance therapy. At a median follow-up of 32 months only 4 of the
      responders required antileukemic treatment. The median survival of responders has
      not been reached, and 3-year survival is 84%. INTERPRETATION AND CONCLUSIONS: r
      HuEPO was efficient in downstaging Rai stage III B-CLL patients, and delayed the
      initiation of antileukemic therapy. Whether this effect can be translated into
      better survival rates remains to be clarified in randomized trials.

PMID- 12010664
TI  - Dose intensification with autologous stem cell transplantation in relapsed and
      resistant Hodgkin's disease.
AB  - BACKGROUND AND OBJECTIVES: Patients affected by Hodgkin's disease (HD) resistant
      to induction therapy or who have a brief duration of first remission have a poor
      outcome. DESIGN AND METHODS: We retrospectively reviewed the clinical data of 28
      patients affected by Hodgkin's disease who relapsed 6 to 24 months from
      completion of treatment (14 patients) or who were refractory to first-line
      therapy or relapsed very early (14 patients). All the 28 patients were treated
      with salvage chemotherapy plus a conditioning regimen followed by peripheral
      blood stem cell transplant (PBCST) or autologous bone marrow transplant (ABMT).
      RESULTS: At a median follow-up of 35.5 months (range 14-119), of the 14 patients
      responding to first-line therapy but who relapsed > 6 months off therapy, 10
      (72%) are alive, well and in complete remission (CR), 2 (14%) are alive with
      disease at 39 and 83 months from transplant, and 2 (14%) died 26 and 63 months
      after their transplant from acute myeloid leukemia and HD, respectively. At a
      median follow-up of 39 months, the overall survival (OS) is 68% and the event
      free survival (EFS) is 56%. At a median follow-up of 30 months (1-98), of the 14
      patients refractory to first-line therapy or who relapsed very early, 9 (64%) are
      alive in CR, 1 (7%) is alive with disease and 4 (29%) have died of their disease
      (3 patients) or myelodysplastic syndrome (1 patient). The OS is 58% and the EFS
      is 52%. There are no statistically significant differences in terms of OS and EFS
      between the two groups of patients. INTERPRETATION AND CONCLUSIONS: Our study
      shows that salvage chemotherapy followed by a conditioning regimen and
      autotransplant is an effective, feasible and well-tolerated scheme of therapy not
      only for patients with HD who relapse after first-line treatment, but also for
      those resistant to first-line treatment.

PMID- 12010665
TI  - Factor XI deficiency in Iranians: its clinical manifestations in comparison with
      those of classic hemophilia.
AB  - BACKGROUND AND OBJECTIVES: In patients with factor XI(FXI) deficiency the
      bleeding tendency is poorly correlated with plasma factor levels. The purpose of
      this study was to evaluate whether or not this discrepancy is also present in a
      large series of patients from Iran, a previously unexplored ethnic group. DESIGN
      AND METHODS: In 28 FXI - deficient patients bleeding symptoms and their relation
      to FXI levels were compared with those of 100 patients with factor VIII
      (FVIII)deficiency (classic hemophilia), matched for severity of factor
      deficiency. RESULTS: Spontaneous bleeding was definitely less frequentin FXI
      deficiency than in hemophilia, whereas postoperative and post-traumatic bleeding
      occurred with comparable frequencies. Among FXI-deficient patients the severity
      of symptoms was poorly correlated with FXI levels, mildly deficient patients
      bleeding almost as frequently as those severely deficient. In contrast, in
      patients with classic hemophilia there was a close relation between the severity
      of bleeding and degree of FVIII deficiency. INTERPRETATION AND CONCLUSIONS: As in
      other ethnic groups, in Iranians factor XI deficiency is less severe than classic
      hemophilia and the bleeding tendency is poorly correlated to plasma factor
      levels.

PMID- 12010666
TI  - Normalization rates of compression ultrasonography in patients with a first
      episode of deep vein thrombosis of the lower limbs: association with recurrence
      and new thrombosis.
AB  - BACKGROUND AND OBJECTIVES: Delayed thrombus regression after a first episode of
      deep vein thrombosis (DVT) of the inferior limbs has been implicated in the
      development of the post-thrombotic syndrome. Whether normalization of vein
      segments involved in the index DVT has prognostic significance with respect to
      the probability of DVT recurrence or new thrombosis is currently unknown. In this
      study, we prospectively monitored thrombus regression in consecutive patients
      with symptomatic and asymptomatic DVT. Factors affecting normalization rates and
      the relationship between previous normalization and DVT recurrence or new
      thrombosis were explored. DESIGN AND METHODS: One hundred and seventy-nine
      patients with a first episode of symptomatic DVT of the lower limbs (38 with
      cancer) and 104 patients with DVT occurring after hip replacement surgery were
      serially monitored by real time B-mode compression ultrasonography (C-US) over a
      period of 12 months (months 1, 3, 6 and 12). C-US normalization of popliteal and
      femoral venous segments was arbitrarily assigned to be residual thrombus
      occupying, at maximum compressibility, less than 40% of the vein area in the
      absence of compression. RESULTS: In patients with no DVT recurrence or new
      thrombosis, C-US normalization was observed at 12 months in 100% of 99 patients
      with post-operative DVT, in 59% of 134 cancer-free symptomatic DVT outpatients
      and in 23.3% of 30 symptomatic DVT outpatients with cancer (p = 0.0001).
      Independent negative effects on the probability of C-US normalization were
      observed for younger age (p <0.05), for the outpatient presentation of the index
      DVT (p 0.017), for DVT involving the entire femoro-popliteal axis (p 0.05), and
      for the presence of cancer (p 0.05). DVT recurrence or new thrombosis was
      observed in 5 patients with post-operative DVT (4.8%), in 7 cancer-free patients
      with symptomatic DVT (5.0%) and in 8 patients with cancer (21.1%). Only 4 of
      these patients had shown normalization of their index DVT prior to the event. The
      presence of cancer was the only significant predictor of DVT recurrence and/or
      new thrombosis occurring within 3 months from the index DVT (OR = 4.90, p =
      0.002). The absence of previous C-US normalization was the only predictor of
      recurrence or new thrombosis occurring after 3 and 6 months from the index DVT
      (OR 5.26, p 0.027). INTERPRETATION AND CONCLUSIONS: Absence of C-US normalization
      after a first episode of DVT appears to be a factor favoring recurrence or new
      thrombosis and may be relevant to the optimal duration of oral anticoagulant
      treatment.

PMID- 12010667
TI  - High versus low doses of unfractionated heparin for the treatment of superficial
      thrombophlebitis of the leg. A prospective, controlled, randomized study.
AB  - BACKGROUND AND OBJECTIVES: The optimal treatment of superficial thrombophlebitis
      of the leg is undefined. The main study objective was to assess the efficacy and
      safety of unmonitored high doses as compared to low doses of unfractionated
      heparin (UFH) for prevention of venous thromboembolic complications in patients
      with superficial thrombophlebitis of the thigh. DESIGN AND METHODS: Sixty
      consecutive patients with acute thrombophlebitis of the great saphenous vein, as
      assessed by ultrasonography, were randomized to subcutaneous injection twice
      daily of UFH in high unmonitored doses (12,500 IU for one week followed by 10,000
      IU) or prophylactic doses (5,000 IU) for four weeks. The rate of asymptomatic
      involvement of the deep venous system and/or symptomatic thromboembolic events
      during a six-month follow-up period was assessed and compared between the two
      study groups. RESULTS: Six of the 30 patients (20.0 %; 95% CI, 7.7 to 38.6)
      randomized to low-dose UFH developed symptomatic or asymptomatic events as
      compared to 1 of the 30 patients (3.3%; 95% CI, 0.07 to 17.2) who received high
      dose UFH (p=0.05 by one-sided Fisher's exact test). No patient experienced major
      bleeding complications in either group. INTERPRETATION AND CONCLUSIONS: The
      results of this study suggest that in patients with acute thrombophlebitis of the
      thigh unmonitored high doses of UFH are more effective than prophylactic doses of
      UFH for prevention of venous thromboembolic complications and do not enhance the
      risk of bleeding complications.

PMID- 12010668
TI  - Invasive pulmonary aspergillosis in patients with hematologic malignancies:
      survival and prognostic factors.
AB  - BACKGROUND AND OBJECTIVES: Despite improvements made in its early diagnosis and
      effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating
      opportunistic infection. In this retrospective study we have reviewed all
      consecutive cases of IPA diagnosed in adult patients with hematologic
      malignancies in our center from 1995 to 2000 to determine survival and prognostic
      factors. DESIGN AND METHODS: Forty-one patients were included in the study. Ante
      mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19
      probable and 8 possible cases; all these last eight patients were later upgraded
      to definite IPA at post-mortem examination. Clinical charts were reviewed and
      factors possibly affecting the outcome of IPA were analyzed. RESULTS: All but two
      patients received chemotherapy and/or immunosuppresive therapy before the onset
      of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation
      [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (<
      0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT
      patients were receiving corticosteroids for graft-versus-host-disease. All but
      two patients received antifungal treatment for IPA. The median delay from
      diagnosis to start of therapy was two days (range 0-20). The median follow-up
      after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61
      months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to
      55%). Thirty-three patients died during follow-up and IPA was implicated in the
      patients' death in 24 cases (75%). In multivariate analysis prolonged survival
      was associated with recovery of neutropenia during treatment (p = 0.001) and not
      having received an allogeneic SCT (p = 0.003). INTERPRETATION AND CONCLUSIONS:
      Despite prompt initiation of antifungal therapy, survival of patients with a
      hematologic malignancy and IPA is currently low. Perhaps the introduction of more
      sensitive diagnostic methods will allow the onset of intensive therapy prior to
      the appearance of more advanced clinical symptoms and/or radiological signs, and
      the time will come to test whether earlier and more intensive therapy will
      improve survival.

PMID- 12010670
TI  - Update on chronic hepatitis C in hemophiliacs.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) infection is an important
      cause of morbidity and mortality in patients affected by hereditary bleeding
      disorders and treated with non-virus inactivated clotting factor concentrates
      during the 1970s. INFORMATION SOURCES: In this review, we briefly report the
      present knowledge about HCV infection in hemophilic patients. The natural course
      of hepatitis C virus infection in hemophiliacs is described, by analyzing the
      prevalence of HCV infection, the genotype distribution and the risk factors
      involved in the progression of chronic hepatitis into severe liver disease such
      as cirrhosis, liver decompensation and hepatocellular carcinoma. STATE OF THE ART
      AND PERSPECTIVES: We focus on the most important advances in the treatment of
      hepatitis C in hemophiliacs.

PMID- 12010669
TI  - Chronic disseminated candidiasis in patients with hematologic malignancies.
      Clinical features and outcome of 29 episodes.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the characteristics of patients affected
      by hematologic malignancies who developed a chronic disseminated candidiasis
      (CDC), and to ascertain the factors that influenced the outcome, in a
      retrospective study conducted between January 1990 and December 2000, in 4
      Hematology Divisions. DESIGN AND METHODS: CDC was diagnosed by clinical features
      combined with radiological and/or histologic and/or microbiological data.
      RESULTS: Twenty-eight patients (male/female 14/14; average age 42 years, range 12
      67) developed a CDC. Twenty had acute myeloid leukemia, 5 had acute lymphocytic
      leukemia and 3 had non-Hodgkin's lymphoma. All patients received chemotherapy,
      including cytarabine for 21 of them (75%). Before the infection, 22 patients
      (79%) were neutropenic (absolute neutrophil count < 0.5 x 10(9)/L) for an average
      of 20 days (8-36), but at CDC diagnosis only 3 patients (11%) were neutropenic.
      Twenty-two patients (75%) received antifungal prophylaxis for an average of 15
      days (10-60). Before diagnosis of CDC, 9 patients (32%) had a candidemia. The
      sites compromised by CDC were: liver in 27 patients (96%) and/or spleen in 11
      patients (38%). Ten patients had other organs involved: lung in 6 patients (21%),
      kidney in 4 patients (14%), other sites 2 patients (7%). Abdominal
      ultrasonography was positive in 96% of patients (27/28), and abdominal computed
      tomography-scan was positive in 100% of cases in which it was performed (21/21).
      Liver biopsy was positive in 10/15 patients (67%). The main signs and symptoms
      were: fever 86%, abdominal pain 54%, diarrhea 32%, tenderness 25%, vomiting 25%,
      jaundice 29%, dysphagia 7%. Among chemical analyses, the most sensitive test was
      alkaline phosphatase, with a 3-5-fold increase in 24 patients (86%); an increase
      of liver transaminases and g-glutamyl transferase was observed in less than 50%
      of patients. By 30 days after diagnosis 4 patients had died, 1 from infection,
      and 3 progression of the hematologic malignancy without signs of active CDC.
      Within 3 months from diagnosis 14 out of the remaining 24 patients (58%) received
      further chemotherapy: in particular, 2 patients underwent transplantation
      procedures. INTERPRETATION AND CONCLUSIONS: In our experience CDC is not a fatal
      complication of patients with hematologic malignancy, on the contrary to that
      observed for other fungal infections (i.e. aspergillosis, candidemia),
      characterized by a higher mortality rate. The major problem of this fungal
      complication is correlated to the delay in the following treatment for the
      hematologic malignancy with a high risk of progression of malignancy.

PMID- 12010671
TI  - The characteristics of megaloblastic anemia associated with thalassemia.

PMID- 12010672
TI  - Novel erythropoiesis stimulating protein exerts an effect on platelet function in
      uremia equivalent to that exerted by recombinant human erythropoietin.

PMID- 12010673
TI  - Low affinity and unstable hemoglobin variant caused by AAC-->ATC (Asn-->Ile)
      mutation at codon 108 of the beta-globin gene.

PMID- 12010674
TI  - Two more inv(16) acute myeloid leukemia cases with infrequent CBFbeta-MYH11
      fusion transcript: clinical and molecular findings.

PMID- 12010675
TI  - Intensified induction followed by high-dose therapy with autologous peripheral
      blood stem cell support in poor-prognosis aggressive non-Hodgkin's lymphoma:
      results of a pilot study.

PMID- 12010676
TI  - Performance evaluation of the CoaguChek S system.

PMID- 12010677
TI  - Reliability of measurements of serum alanine transaminase activity and the impact
      on the cut-off value for the selection of blood donors.

PMID- 12010678
TI  - A further case of acute myeloid leukaemia with inv(8)(p11q13) and MOZ-TIF2
      fusion.

PMID- 12010679
TI  - Negative stain for myeloid peroxidase and Sudan black B in acute promyelocytic
      leukemia (APL) cells: report of two patients with APL variant.

PMID- 12010680
TI  - Early onset of evans syndrome following autologous peripheral blood progenitor
      cell transplantation in a child.

PMID- 12010681
TI  - Elevated levels of factor VIII:C, oral contraceptives and thrombosis: report of a
      case.

PMID- 12010682
TI  - Secondary acute monocytic leukemia with a translocation t(8;22)(p11;q13).

PMID- 12010683
TI  - The place of rituximab in the treatment algorithm for post-stem cell transplant
      autoimmune hemolytic anemia.

PMID- 12010684
TI  - Can (18)F-FDG PET after first cycle chemotherapy predict the efficacy of therapy
      in Hodgkin's disease?

PMID- 12010685
TI  - Leukocytosis and hyperleptinemia in obesity: is there a link?

PMID- 12010686
TI  - Occurrence of a FAB-M1 AML in a child during treatment of APL: emergence of an
      immature clone or a therapy related-AML?

PMID- 12010687
TI  - Autosomal dominant macrothrombocytopenia with ineffective thrombopoiesis.

PMID- 12010688
TI  - Competency-based graduate medical education? Of course! But how should competency
      be assessed?

PMID- 12010689
TI  - Shifting paradigms: from Flexner to competencies.
AB  - Realizing medical education is on the brink of a major paradigm shift from
      structure- and process-based to competency-based education and measurement of
      outcomes, the authors reviewed the existing medical literature to provide
      practical insight into how to accomplish full implementation and evaluation of
      this new paradigm. They searched Medline and the Educational Resource Information
      Clearinghouse from the 1960s until the present, reviewed the titles and abstracts
      of the 469 articles the search produced, and chose 68 relevant articles for full
      review. The authors found that in the 1970s and 1980s much attention was given to
      the need for and the development of professional competencies for many medical
      disciplines. Little attention, however, was devoted to defining the benchmarks of
      specific competencies, how to attain them, or the evaluation of competence. Lack
      of evaluation strategies was likely one of the forces responsible for the three
      decade lag between initiation of the movement and wide-spread adoption. Lessons
      learned from past experiences include the importance of strategic planning and
      faculty and learner buy-in for defining competencies. In addition, the benchmarks
      for defining competency and the thresholds for attaining competence must be
      clearly delineated. The development of appropriate assessment tools to measure
      competence remains the challenge of this decade, and educators must be
      responsible for studying the impact of this paradigm shift to determine whether
      its ultimate effect is the production of more competent physicians.

PMID- 12010690
TI  - One school's strategy to assess and improve the vitality of its faculty.
AB  - The authors report how one medical school took an evidence-based, collaborative
      approach to assessing and improving faculty vitality by building on previous
      research and including important shareholders (e.g., faculty and administrators).
      In 1999, the dean and faculty senate asked all full-time faculty (615) at the
      University of Minnesota Medical School-Twin Cities to complete a survey to (1)
      identify vitality areas (individual, institutional, or leadership) in which the
      school was strong and ones that needed improvement, (2) identify strategies for
      addressing weak areas, and (3) provide a baseline against which to measure the
      impact of any vitality efforts initiated. The survey was based on features that
      research studies have found to be associated with academic productivity. Seventy
      six percent responded. Summaries of the survey findings were prepared for use at
      the school level, department level, and special group level (e.g., women,
      clinical-scholar-track faculty). Three key school-level findings were that (1)
      there is a disconnect between the stated vision of the school and the
      departments' visions and actions, (2) there is not enough time for scholarly
      activity, particularly in the clinical departments, and (3) faculty lack the
      support of a collegial atmosphere and appreciation for the work they do. In
      response to the survey's findings every department identified priority faculty
      needs and initiated tailored development strategies. School-wide strategies were
      also initiated to address faculty needs common across departments and needs
      unique to special groups. Together these strategies provide a multi-level,
      systematic approach to maintaining faculty vitality.

PMID- 12010691
TI  - Helping medical school faculty realize their dreams: an innovative, collaborative
      mentoring program.
AB  - Junior faculty wishing to achieve successful careers in academic medicine face
      many challenges. To facilitate faculty in their career development, the authors
      implemented and evaluated an innovative collaborative, or peer-group, mentoring
      program at their medical school. Based on Rogerian and adult learning principles,
      the program incorporated development of skills in key areas for career
      development, a structured values-based approach to career planning, and
      instruction in scholarly writing. The 80-hour program has so far been conducted
      twice over two academic years (1999-2001) with 18 faculty (50% women).
      Quantitative and qualitative methods were used in the evaluation. Program
      attendance was 89%. All participants completed a written academic development
      plan, an exercise they rated as valuable. They also completed an average of one
      to three manuscripts for publication. Evaluation data highlighted the critical
      nature of a supportive learning environment and the reasons participants chose to
      attend the program consistently. Key meaningful outcomes for most participants
      were: (1) identification of their core values; (2) a structured process of short-
      and long-term career planning based on these core values; (3) the development of
      close, collaborative relationships; (4) development of skills in such areas as
      gender and power issues, negotiation and conflict management, scholarly writing,
      and oral presentation, and (5) improved satisfaction linked to participants'
      decisions to remain in academic medicine. Participants developed a sense of
      personal transformation and empowerment. The authors conclude that collaborative
      mentoring offers a new approach to faculty development that addresses limitations
      of traditional approaches in a satisfying and cost-effective way.

PMID- 12010692
TI  - Teaching the teachers: helping faculty in a family practice residency improve
      their informatics skills.
AB  - Faculty members in family practice residencies are increasingly being asked to
      help residents develop skills in the use of informatics and evidence-based
      medicine (EBM). In order to do this successfully the teachers themselves must be
      skilled in the use of these tools. Recognizing the need for such training, the
      Maine Medical Center Family Practice Residency Program designed a faculty
      development project to increase knowledge and skills in the use of information
      technology. This project, which was carried out in 1999-2001, utilized a
      multifaceted approach that included improving the residency's technology
      infrastructure, conducting two instructional workshops, and offering EBM
      mentoring for preceptors. Faculty members also designed and carried out
      independent informatics projects. Pre- and post-project assessments of faculty
      members demonstrated a significant improvement in computer and EBM skills, and
      informal feedback from residents indicates that these skills have been
      successfully applied to the faculty members' teaching of residents and their
      practice of family medicine. This project had a positive impact on the faculty
      members in the residency program, increasing both their ability to employ
      information technology in individual and group teaching sessions and their use of
      EBM in clinical practice. Also, the culture within the residency program has been
      changed to one of utilizing computers and the Internet as principal resources for
      up-to-date information.

PMID- 12010694
TI  - How best to evaluate clinician-educators and teachers for promotion?
AB  - The challenge of how best to evaluate educational scholars (and specifically,
      clinician-educators) and teachers for promotion continues to confront academia.
      While the work of educational scholars and teachers often overlaps, the terms for
      justifying their promotion differ substantially. In each case, the author
      maintains that evaluation should be oriented to evidence of the impact of their
      work. Educational scholars can be assessed mainly by objective impact, whereas
      the evidence for the impact of teachers should include profound, subjective
      effects on individual learners. For example, for clinician-educators engaged in
      scholarly work, the impact of that work can be identified in terms of changes in
      educational methods, career commitments, and practices (all intermediate
      outcomes), and even health outcomes. For teachers, in addition to customary
      criteria such as critical thinking, depth of knowledge, communication ability,
      and personal engagement, learners can be asked about the deep influence of these
      teachers. The author states his case for these principles, and also presents an
      innovative tool, the "impact map," as a way of graphically portraying the track
      record of an individual clinician-educator. Such maps are more vivid than
      narrative testimonials in organizing and displaying evidence of impact over time.
      This tool, combined with the author's other suggestions to assist the promotion
      process for educators and teachers, is aimed at fostering a greater emphasis on
      outcomes in assessing both clinician-educators and teachers to achieve greater
      rigor and fairness.

PMID- 12010695
TI  - Status of faculty affairs and faculty development offices in U.S. medical
      schools.
AB  - PURPOSE: To collect baseline data and describe how medical schools handle faculty
      affairs and faculty development responsibilities. METHOD: In January 2000, the
      authors surveyed faculty affairs designees at 125 U.S. medical schools, using a
      questionnaire developed in consultation with a group of faculty affairs
      professionals. RESULTS: The responding 76 medical schools (61%) support over four
      times as many offices of faculty affairs as faculty development offices. Core
      functions of faculty affairs offices include administrative support for
      appointments, promotions, and tenure committees; faculty information and
      policies; faculty governance processes; and department chairs' recruitment
      support and personnel management issues. CONCLUSION: While a consensus is
      emerging about the functions of a faculty affairs office, no school has a
      comprehensive faculty development system, in contrast to most industries, which
      must be more forward-looking to compete for talent.

PMID- 12010696
TI  - A nationwide study of the influence of faculty development programs on colleague
      relationships.
AB  - PURPOSE: Academic colleague relationships (CRs) promote career development and
      professional advancement. Some primary care faculty development programs (FDPs)
      have begun to examine their influence on enrollees' colleague development. Using
      a nationwide sampling, the authors examined the effects of FDPs on the formation
      and benefits of enrollees' academic CRs. METHOD: The authors conducted a
      retrospective, cross-sectional study in two phases, each relying on written
      questionnaires. In phase one, program details and enrollee rosters were provided
      by directors at FDPs funded by the U.S. Department of Health and Human Services,
      Health Resources and Services Administration, from 1994 through 1997. In phase
      two, family medicine physicians enrolled during these years provided feedback on
      their socialization skills and formation of relationships with career-supportive
      colleagues (mentors, peers, and academic consultants), as well as academic
      achievements and products these colleagues aid. RESULTS: Of the 52 directors, 37
      (71%) provided FDP information and enrollee rosters. Of the 543 enrollees, 351
      (65%) reported initiating or strengthening an average of nine CRs due to program
      participation: three peers, two mentors, one academic consultant, and three
      additional colleagues perceived available for future career support. Colleague
      gains were positively associated with academic socialization. Colleagues actively
      assisted with academic achievements and products, and provided links to networks
      of regional and national scholars. CONCLUSION: FDPs help enrollees build career
      important relationships with peers, mentors, and academic consultants who enhance
      socialization skills and contribute to academic advancement.

PMID- 12010697
TI  - A simple tool to evoke physicians' real training needs.
AB  - Commonly used methods for identifying the training needs of general practitioners
      do not enable the real needs felt during interviews with patients during office
      visits to be detected. In this study, the authors evaluate how physicians' use of
      a personal-office-visit diary affects the level of specificity of their expressed
      training needs. In 1999, the authors carried out a controlled intervention trial
      using a random sample of 1,038 general practitioners from a region of France,
      randomized to intervention and control groups. The practitioners in the
      intervention group were asked to identify their training needs using a personal
      office-visit diary. The level of specificity for their expressed needs was
      compared with that of the expressed needs of the practitioners in the control
      group. The use of the diary was associated with a significantly higher level of
      specificity in the training needs identified by the general practitioners who
      participated. Independent of the intervention, practitioners under 40 years of
      age, those in urban practice, and those who were members of a continuing medical
      education (CME) association expressed their training needs with higher
      specificity. The personal-office-visit diary would seem to be a simple,
      inexpensive, and useful tool for more specifically identifying training needs,
      which could help establish more appropriate and better-targeted training
      programs. However, it should be assessed further by those involved in CME for
      general practitioners.

PMID- 12010699
TI  - Medicine and the arts. Haiku, by Basho; Old Lady Patient, by Cortney Davis;
      commentary by Johanna Shapiro.

PMID- 12010702
TI  - The empirical validity of straight-line responses on a clinical evaluation form.
AB  - PURPOSE: Many preceptors fill out students' clerkship-performance forms with all
      items marked with the maximum value. Because items are usually designed to
      measure somewhat specific behaviors, the authors questioned the validity of
      straight-line five (SL5) responses, and conducted an empirical validity study to
      investigate the measurement properties of these SL5 forms. METHOD: In 1999-00 the
      authors undertook a correlation study and a generalizability study to assess the
      measurement characteristics of the SL5 forms. For the correlation study, they
      calculated mean scores for each of 168 students across forms, excluding the SL5
      forms, then correlated this mean with the proportion of straight-line forms the
      student received. They conducted a generalizability analysis with and without the
      straight-line forms to determine the impact on score reliability. RESULTS: The
      proportion of SL5 forms was significantly correlated (r =.48, p <.0001) with the
      mean student score. Inclusion of the SL5 forms did not negatively affect the
      reliability of the mean score. CONCLUSION: The SL5 forms appear to be valid
      ratings of students' performances. An informal comparison of the comments on SL5
      forms and those not displaying this format supported this conclusion.

PMID- 12010703
TI  - The impact of a brief interclerkship about substance abuse on medical students'
      skills.
AB  - PURPOSE: To examine the immediate and delayed impact of an intensive one- or two
      day interclerkship on substance abuse (SA) for third-year medical students. The
      program is a response to the problem of inadequacy of substance abuse education
      in the standard curriculum. METHOD: Each year since 1997-98 all third-year
      students at the University of Massachusetts Medical School have participated in a
      one- or two-day SA interclerkship to enhance their knowledge and competence with
      SA assessment and brief intervention. Students' knowledge, attitudes, and
      confidence were assessed immediately before and after the interclerkship. In
      addition, during 1998-99, each student's clinical skills in SA assessment and
      intervention were evaluated at the completion of the student's six-week
      psychiatry clerkship using objective standardized clinical examinations (OSCEs)
      with two simulated patients, one with and one without active SA issues. Students
      who took the psychiatry clerkship in the first half of the year had not yet
      participated in the interclerkship. Students' pooled performances before and
      after the interclerkship were compared. RESULTS: Students' attitudes toward and
      knowledge about SA disorders and their confidence about SA assessment and
      intervention all showed significant positive changes immediately after the
      interclerkship. The OSCE performance data demonstrated a significant sustained
      improvement in clinical skills in SA assessment and intervention as measured up
      to six months following the interclerkship. CONCLUSION: These data suggest that
      brief intensive training in SA during the clinical years of medical school can
      have a positive and lasting impact on students' clinical performances.

PMID- 12010704
TI  - Resources in bioethics at osteopathic medical schools.
AB  - PURPOSE: Medical students must have some exposure to bioethics, whether it be at
      the undergraduate or the postgraduate level. The authors sought to determine the
      range and ranking of topics taught in bioethics courses at U.S. osteopathic
      medical schools. METHOD: A qualitative study using a repeated-measures design was
      used to determine curricular offerings at all 19 U.S. osteopathic medical
      schools. Nominal groups were held to identify an initial topics list. A modified
      reactive Delphi technique was constructed and three survey iterations were
      administered. RESULTS: Bioethics is taught in all osteopathic medical schools,
      although the numbers of hours dedicated to the subject in the course of a four
      year curriculum vary greatly (range 0-40). To further differentiate a curriculum
      in bioethics, the respondents were asked to rank bioethics topics as essential,
      foundational, or peripheral to the undergraduate medical curriculum. A total of
      16 topics, including confidentiality, informed consent, truth-telling, death and
      dying, palliative care, and refusal of care, were identified as "essential" for a
      bioethics curriculum. CONCLUSIONS: Bioethics is taught at osteopathic medical
      schools, but further studies are needed to recommend guidelines to standardize
      the curriculum.

PMID- 12010705
TI  - Ethics education in U.S. medical schools: a study of syllabi.
AB  - PURPOSE: Despite attempts to describe the "ideal" medical ethics curriculum, few
      data exist describing current practices in medical ethics education to guide
      curriculum directors. This study aimed to determine the scope and content of
      required, formal ethics components in the curricula of U.S. medical schools.
      METHOD: A questionnaire sent to all curriculum directors of four-year medical
      schools in the U.S. (n = 121) requested course syllabi for all required, formal
      ethics components in the four-year curriculum. Syllabi were coded and analyzed to
      produce a profile of course objectives, teaching methods, course contents, and
      methods for assessing students. RESULTS: Questionnaires were returned by 87
      representatives of the schools (72%). A total of 69 (79%) required a formal
      ethics course, and 58 (84%) provided their ethics course syllabi. Analysis and
      codification of all syllabi identified ten course objectives, eight teaching
      methods, 39 content areas, and six methods of assessing students. The means for
      individual schools were three objectives, four teaching methods, 13 content
      areas, and two methods of assessment. The 58 syllabi either required or
      recommended 1,191 distinct readings, only eight of which were used by more than
      six schools. CONCLUSIONS: Ethics education is far from homogeneous among U.S.
      medical schools, in both content and extensiveness. While the study of syllabi
      demonstrates significant areas of overlap with recent efforts to identify an
      "ideal" ethics curriculum for medical students, several areas of weakness emerged
      that require attention from medical educators.

PMID- 12010707
TI  - A prospective, randomized controlled study of computer-assisted learning in
      parasitology.
AB  - PURPOSE: To compare, using a prospective, randomized controlled study, three
      methods of teaching a medical school parasitology course: computer-based
      instruction, traditional lecture-based instruction, and a combination of computer
      based and lecture-based instruction. METHOD: A single class of the University of
      Utah School of Medicine was randomized into three study groups for the second
      year parasitology course. The computer group (n = 29) used a locally developed
      interactive parasitology computer program; the lecture group (n = 32) had
      traditional lectures, and the combined group (n = 33) used both the computer
      program and lectures. Students' knowledge was assessed using a pretest, a final
      examination, and a posttest administered four months after the course. Students
      also used logs to track the amounts of time they spent studying. Their
      impressions and course evaluations were collected using a standardized course
      evaluation form. RESULTS: The groups' scores on the pretest, final examination,
      and posttest were not statistically significantly different. Students in the
      computer group averaged 26.8 hours of studying over the two-week course compared
      with 32.1 hours in the lecture group and 32.7 hours in the combined group. The
      difference in study times between the computer and combined groups yielded a
      significant p value of 0.036. Students were generally positive about the course
      and the computer program. CONCLUSION: Students can learn parasitology from
      computer-based instruction as effectively as from traditional lecture-based
      instruction, and they can do so in less time.

PMID- 12010710
TI  - The UCSF Academy of Medical Educators.

PMID- 12010706
TI  - Shared decision making: views of first-year residents and clinic patients.
AB  - PURPOSE: Patients' and physicians' views of their roles in decision making have
      implications for patient care and medical education. This study was designed to
      determine perspectives of residents and patients on the amount of control each
      should have in health care decisions. METHOD: Data were collected from a self
      administered questionnaire of 45 first-year residents and a parallel structured
      interview with 92 patients from three resident clinics. Information Seeking (IS)
      and Decision Making (DM) scales from the Autonomy Preference Index were
      supplemented by five clinical scenarios focused on decisions concerning
      hypertension, depression, cholecystectomy, hysterectomy, and prostate cancer.
      Analysis of variance (ANOVA) and repeated-measures ANOVA were used to test for
      significant differences in scores. RESULTS: Patients' and residents' mean scores
      on IS were practically equivalent, indicating strong desire for information
      sharing. For DM, patients indicated a desire for slightly less than equal control
      in decisions, while residents thought patients should have a more than equal
      role. Given the specific clinical scenarios, the picture varied. Patients wanted
      equal roles in the hypertension, depression, and prostate cancer scenarios, while
      residents wanted to have more control in these decisions. Conversely, patients
      wanted greater control in the hysterectomy and cholecystectomy scenarios, and
      residents wanted a less than equal role in these decisions. Patients thought
      consultants such as surgeons desired the same role as their physicians, but
      residents assumed consultants wanted more control. CONCLUSIONS: Patients from a
      disadvantaged population indicated a strong desire for information and
      participation in making decisions about their care. Understanding the
      similarities and discrepancies in patients' and first-year residents'
      perspectives on shared decision making can have consequences for the patient
      physician relationship and medical education.

PMID- 12010711
TI  - The Academies Collaborative: sharing a new model for medical education.

PMID- 12010712
TI  - A workshop on teaching beliefs.

PMID- 12010713
TI  - Taking a chance with your next teaching opportunity.

PMID- 12010714
TI  - Junior faculty performance appraisal in general internal medicine.

PMID- 12010715
TI  - Building geriatrics curricula in medical and surgical house officer programs
      through faculty development.

PMID- 12010716
TI  - Faculty development workshop: preparing for your promotion.

PMID- 12010717
TI  - Faculty development online: an observation and feedback module.

PMID- 12010718
TI  - Web-based orientation for new faculty members.

PMID- 12010719
TI  - A workshop on mentoring across gender and culture lines.

PMID- 12010720
TI  - Teaching as research: an option to enhance teaching skills.

PMID- 12010721
TI  - Curriculum in physician-patient communication skills for new faculty.

PMID- 12010722
TI  - A learner-centered academic career development curriculum.

PMID- 12010723
TI  - Training the masses: a resident teaching skills workshop during housestaff
      orientation.

PMID- 12010724
TI  - A research laboratory methods course for medical subspecialty residents.

PMID- 12010725
TI  - A curriculum in medical economics for residents.

PMID- 12010726
TI  - A retreat for first-year medicine fellows.

PMID- 12010727
TI  - Residents' knowledge of medication prices.

PMID- 12010728
TI  - Residents' teaching of anatomy in the laboratory: enhancement of student
      learning.

PMID- 12010729
TI  - Residents teaching medical students: incentive program.

PMID- 12010730
TI  - Playing the role of a bioethics committee: creative approaches to teaching
      culture and bioethics.

PMID- 12010731
TI  - A required interclerkship on multiculturalism for third-year medical students.

PMID- 12010732
TI  - Does spirituality matter in patient care? Establishing relevance and generating
      skills.

PMID- 12010733
TI  - Critical appraisal of alternative therapies: a mini-course.

PMID- 12010734
TI  - Adaptational responses to hypoxia.

PMID- 12010735
TI  - The mouse is a small rabbit.

PMID- 12010736
TI  - Autonomic control of blood pressure in mice: basic physiology and effects of
      genetic modification.
AB  - Control of blood pressure and of blood flow is essential for maintenance of
      homeostasis. The hemodynamic state is adjusted by intrinsic, neural, and hormonal
      mechanisms to optimize adaptation to internal and environmental challenges. In
      the last decade, many studies showed that modification of the mouse genome may
      alter the capacity of cardiovascular control systems to respond to homeostatic
      challenges or even bring about a permanent pathophysiological state. This review
      discusses the progress that has been made in understanding of autonomic
      cardiovascular control mechanisms from studies in genetically modified mice.
      First, from a physiological perspective, we describe how basic hemodynamic
      function can be measured in conscious conditions in mice. Second, we focus on the
      integrative role of autonomic nerves in control of blood pressure in the mouse,
      and finally, we depict the opportunities and insights provided by genetic
      modification in this area.

PMID- 12010737
TI  - A practical guide to evaluating cardiovascular, renal, and pulmonary function in
      mice.
AB  - The development and widespread use of genetically altered mice to study the role
      of various proteins in biological control systems have led to a renewed interest
      in methodologies and approaches for evaluating physiological phenotypes. As a
      result, cross-disciplinary approaches have become essential for fully realizing
      the potential of these new and powerful animal models. The combination of
      classical physiological approaches and modern innovative technology has given
      rise to an impressive arsenal for evaluating the functional results of genetic
      manipulation in the mouse. This review attempts to summarize some of the
      techniques currently being used for measuring cardiovascular, renal, and
      pulmonary variables in the intact mouse, with specific attention to practical
      considerations useful for their successful implementation.

PMID- 12010738
TI  - Vampire bat, shrew, and bear: comparative physiology and chronic renal failure.
AB  - In the typical mammal, energy flux, protein metabolism, and renal excretory
      processes constitute a set of closely linked and quantitatively matched
      functions. However, this matching has limits, and these limits become apparent
      when animals adapt to unusual circumstances. The vampire bat and shrew have an
      extremely high protein intake, and the glomerular filtration rate (GFR) is not
      commensurate with the large urea load to be excreted. The vampire bat is
      chronically azotemic (blood urea concentration 27-57 mmol/l); yet there is no
      information as to how this animal has adjusted to such an azotemic internal
      environment. A high protein intake should also lead to chronic glomerular
      hyperfiltration; yet neither animal appears to develop progressive renal failure.
      The American black bear, on the other hand, has adapted to a prolonged period
      without intake or urine output. Despite continued amino acid catabolism with urea
      production, this mammal is able to completely salvage and reutilize urea nitrogen
      for protein synthesis, although the signals that initiate this metabolic
      adaptation are not known. The vampire bat, shrew, and bear are natural models
      adapted to circumstances analogous to chronic renal failure. Unraveling these
      adaptations could lead to new interventions for the prevention/treatment of
      chronic renal failure.

PMID- 12010739
TI  - Blocking cerebrospinal fluid absorption through the cribriform plate increases
      resting intracranial pressure.
AB  - Cerebrospinal fluid (CSF) drains through the cribriform plate (CP) in association
      with the olfactory nerves. From this location, CSF is absorbed into nasal mucosal
      lymphatics. Recent data suggest that this pathway plays an important role in
      global CSF transport in sheep. In this report, we tested the hypothesis that
      blocking CSF transport through this pathway would elevate resting intracranial
      pressure (ICP). ICP was measured continuously from the cisterna magna of sheep
      before and after CP obstruction in the same animal. To block CSF transport
      through the CP, an external ethmoidectomy was performed. The olfactory and
      adjacent mucosa were removed, and the bone surface was sealed with tissue glue.
      To restrict our analysis to the cranial CSF system, CSF transport into the spinal
      subarachnoid compartment was prevented with a ligature tightened around the
      thecal sac between C1 and C2. Sham surgical procedures had no significant
      effects, but in the experimental group CP obstruction elevated ICP significantly.
      Mean postobstruction steady-state pressures (18.0 +/- 3.8 cmH(2)O) were
      approximately double the preobstruction values (9.2 +/- 0.9 cmH(2)O). These data
      support the concept that the olfactory pathway represents a major site for CSF
      drainage.

PMID- 12010740
TI  - Troglitazone induces a cellular acidosis by inhibiting acid extrusion in cultured
      rat mesangial cells.
AB  - We studied the effect of troglitazone on cellular acid-base balance and alanine
      formation in isolated rat mesangial cells. Mesangial cells were grown to
      confluency in RPMI 1640 media on 30-mm chambers used to monitor both cellular pH
      using the pH-sensitive dye 2'7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein and
      metabolic acid production as well as glutamine metabolism. Troglitazone (10
      microM) induced a spontaneous cellular acidosis (6.95 +/- 0.02 vs. 7.47 +/- 0.04,
      respectively; P < 0.0001) but without an increase in lactic acid production.
      Alanine production was reduced 64% (P < 0.01) consistent with inhibition of the
      glutamate transamination. These findings pointed to a decrease in acid extrusion
      rather than an increase in acid production as the underlying mechanism leading to
      the cellular acidosis. To test their acid extrusion capabilities, mesangial cells
      were acid loaded with NH and then allowed to recover in Krebs-Henseleit media or
      in Krebs-Henseleit media minus bicarbonate (HEPES substituted), and the recovery
      response (Delta pH(i)/min) was monitored. In the presence of 10 microM
      troglitazone, the recovery response to the NH acid load was virtually eliminated
      in the bicarbonate-buffered media (0.00 +/- 0.001 vs. 0.06 +/- 0.02 pH(i)/min, P
      < 0.0001 vs. control) and reduced 75% in HEPES-buffered media (0.01 +/- 0.01 vs.
      0.04 +/- 0.02 pH(i)/min, P < 0.002 vs. control). These results show that
      troglitazone induces a spontaneous cellular acidosis resulting from a reduction
      in cellular acid extrusion.

PMID- 12010741
TI  - Venous plasma potassium is not associated with maintenance of the exercise
      pressor reflex in humans.
AB  - Increases in the concentration of interstitial potassium concentration during
      exercise may play a role in the modulation of the cardiovascular response to
      exercise. However, it is not known if changes in potassium correlate with indexes
      of muscle reflex engagement. Eight healthy subjects performed dynamic [rhythmic
      handgrip (RHG)] and static handgrip (SHG) exercise at 40% of maximal voluntary
      contraction. Forearm circulatory arrest was performed to assess the
      metaboreceptor component of the exercise pressor reflex. Mean arterial pressure
      (MAP) and muscle sympathetic nerve activity (MSNA) were measured during each
      exercise paradigm. Venous plasma potassium concentrations ([K(+)](V)) were
      measured and used as a surrogate marker for interstitial potassium. [K(+)](V)
      were measured at baseline and at 1-min intervals during dynamic handgrip. During
      SHG, [K(+)](V) were measured at baseline, 30 and 90 s of exercise, and twice
      during forearm circulatory arrest. Mean [K(+)](V) was 3.6 mmol/l at rest before
      both paradigms. During RHG, [K(+)](V) rose by approximately 1.0 mmol/l by min 2
      and remained constant throughout the rest of handgrip. During SHG, [K(+)](V) rose
      significantly at 30 s and rose an additional approximately 1.0 mmol/l by peak
      exercise. MAP and MSNA rose during both exercise paradigms. During posthandgrip
      circulatory arrest (PHG-CA), MSNA and blood pressure remained above baseline.
      [K(+)](V) and MSNA did not correlate during either exercise paradigm. Moreover,
      during PHG-CA, there was clear dissociation of MSNA from [K(+)](V). These data
      suggest that potassium does not play a direct role in the maintenance of the
      exercise pressor reflex.

PMID- 12010742
TI  - Angiotensin II feedback is a regulator of renocortical renin, COX-2, and nNOS
      expression.
AB  - Salt restriction leads to parallel increases of renin, cyclooxygenase-2 (COX-2),
      and neuronal nitric oxide synthase (nNOS) gene expression in the juxtaglomerular
      apparatus of rat kidneys. Because the upregulation of these genes is strongly
      enhanced if salt restriction is combined with inhibition of the renin-angiotensin
      aldosterone system, our study aimed to find out whether the juxtaglomerular
      expressions of renin, COX-2, and nNOS are subject to a common direct negative
      feedback control by ANG II. For this purpose, male Sprague-Dawley rats were fed a
      low-salt diet (0.02% wt/wt) with or without additional treatment with the ANG I
      converting enzyme (ACE) inhibitor ramipril (10 mg x kg body wt(-1) x day(-1)) for
      1 wk, and renocortical renin, COX-2, and nNOS mRNAs were assayed. To narrow down
      possible indirect effects of the ACE inhibitor that may result from insufficient
      aldosterone production, the animals received mineralocorticoid substitution with
      fludrocortisone (6 mg. kg body wt(-1) x day(-1)). Thus mineralocorticoid
      substitution prevented the fall of systolic blood pressure and of glomerular
      filtration induced by ramipril in rats on low-salt diet. Although fludrocortisone
      had no effect on basal renin, COX-2, and nNOS mRNA, it clearly attenuated the
      threefold increases of both renin and COX-2 mRNA in response to low-salt diet. In
      rats on low-salt diet, ramipril further increased renin mRNA ninefold, COX-2 mRNA
      fourfold, and nNOS 2.5-fold in the absence of fludrocortisone. In the presence of
      fludrocortisone, ramipril increased renin mRNA 10-fold, COX-2 mRNA 2.5-fold, and
      nNOS mRNA 2.5-fold. These data indicate that mineralocorticoid substitution
      lowers the overall expression of juxtaglomerular renin and COX-2 during low-salt
      intake and attenuates a further rise of COX-2 expression by ACE inhibition, but
      it does not change the stimulatory effect of ACE inhibition on renin and nNOS
      expression. We conclude that the expression of renin, COX-2, and nNOS in the
      juxtaglomerular apparatus during low-salt diet is markedly limited by a direct
      feedback inhibition through ANG II.

PMID- 12010743
TI  - PGE(2) increases release of substance P from renal sensory nerves by activating
      the cAMP-PKA transduction cascade.
AB  - Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA)
      by a PGE(2)-mediated release of substance P (SP) from renal pelvic nerves. The
      role of cAMP activation in the PGE(2)-mediated release of SP was studied by
      examining the effects of the adenylyl cyclase (AC) activator forskolin and AC
      inhibitor dideoxyadenosine (DDA). Forskolin enhanced the bradykinin-mediated
      release of SP from an isolated rat renal pelvic wall preparation, from 7.3 +/-
      1.3 to 15.6 +/- 3.0 pg/min. PGE(2) at a subthreshold concentration for SP release
      mimicked the effects of forskolin. The EP(2) receptor agonist butaprost, 15
      microM, and PGE(2), 0.14 microM, produced similar increases in SP release, from
      5.8 +/- 0.8 to 17.0 +/- 2.3 pg/min and from 8.0 +/- 1.3 to 21.6 +/- 2.7 pg/min.
      DDA blocked the SP release produced by butaprost and PGE(2). The PGE(2)-induced
      release of SP was also blocked by the PKA inhibitors PKI(14-22) and H-89. Studies
      in anesthetized rats showed that renal pelvic administration of butaprost, 10
      microM, and PGE(2), 0.14 microM, resulted in similar ARNA responses, 1,520 +/-
      390 and 1,170 +/- 270%. s (area under the curve of ARNA vs. time) that were
      blocked by DDA. Likewise, the ARNA response to increased renal pelvic pressure,
      7,180 +/- 710%. s, was blocked by DDA. In conclusion, PGE(2) activates the cAMP
      PKA pathway leading to a release of SP and activation of renal pelvic
      mechanosensory nerve fibers.

PMID- 12010744
TI  - Spatial and developmental regulation of leptin in fetal sheep.
AB  - To better understand the biology of leptin during prenatal life, the
      developmental and spatial regulation of leptin was studied in ovine fetuses.
      Fetal plasma leptin increased steadily between days 40 and 143 postcoitus (PC),
      but it was unrelated to fetal weight or placental weight at day 135 PC. Leptin
      gene expression was detected in fetal brain and liver during most of gestation
      and in fetal adipose tissue after day 100 PC. At day 130 PC, expression in fetal
      perirenal adipose tissue was approximately 10% of maternal expression. In
      contrast, leptin gene expression was never detected in the placenta and other
      uteroplacental tissues. When ewes were fed 55% of requirements between days 122
      and 135 PC, fetal plasma leptin remained constant despite acute reduction in
      maternal concentration. We conclude that fetal plasma leptin originates mostly
      from nonadipose tissue in early pregnancy and, in addition, from fetal adipose
      tissue near term. The role of fetal plasma leptin remains uncertain given the
      lack of nutritional regulation and association with fetal growth.

PMID- 12010745
TI  - Development of an in situ perfused kidney preparation for elasmobranch fish:
      action of arginine vasotocin.
AB  - Acclimation of the European lesser-spotted dogfish Scyliorhinus canicula to
      reduced environmental salinity [85-70% seawater (SW)] induced a significant
      diuresis in addition to a significant decrease in plasma osmolality in vivo. The
      threshold for this diuresis was determined to be 85% SW. Therefore, S. canicula
      acclimated to 85% SW was selected for further study as a diuretic model in the
      development of an in situ perfused kidney preparation. The renal role of arginine
      vasotocin (AVT) in the in situ perfused trunk preparation was investigated. In
      SW, perfusion of 10(-9) and 10(-10) M AVT resulted in a glomerular antidiuresis
      and decreases in tubular transport maxima for glucose and perfusate flow. In 85%
      SW, 10(-10) M AVT had no significant effect on these renal parameters with the
      exception of transport maxima for glucose and perfusate flow. Tubular parameters
      remained unchanged by either 10(-9) or 10(-10) M AVT. The results demonstrate
      that the perfused kidney preparation was a viable tool for the investigation of
      renal parameters in elasmobranch fish and that AVT induced a glomerular
      antidiuresis.

PMID- 12010746
TI  - A homolog of the E3 ubiquitin ligase Rbx1 is induced during hyperosmotic stress
      of salmon.
AB  - Juvenile salmon migrating from freshwater to the marine environment confront a
      marked change in environmental osmolality. Using differential display of mRNA
      expression, we cloned a 1.9-kb cDNA upregulated in isolated tissues of salmon
      exposed to the hyperosmotic stress associated with transition to the dehydrating
      marine environment. The cDNA codes for a 21-kDa protein, salmon hyperosmotic
      protein 21 (Shop21), with 98% identity to Rbx1, an E3 ubiquitin ligase; the
      protein also contains a novel 81-amino acid domain at the NH(2) terminus not
      found in Rbx1. Moderate hyperosmotic stress (24 h at 550 mosmol/kg) increased
      Shop21 transcript 10-fold in branchial lamellae, whereas no upregulation was
      observed under more severe stress (> or = 800 mosmol/kg). Expression of the gene
      also was observed in heart and kidney. Replacement of NaCl with mannitol, but not
      glycerol, also elicited an increase in Shop21 mRNA. Inhibition of the mitogen
      activated protein kinase and mitogen-activated extracellular regulated kinase
      kinase signal transduction pathways failed to blunt the Shop21 response during
      hyperosmotic stress. Shop21 mRNA also accumulated during thermal stress but to a
      lesser extent than heat shock protein 70 mRNA. The potential importance of Shop21
      to the living animal is suggested by marked upregulation of the gene in salmon
      after transfer to seawater. The results of these investigations suggest that
      Shop21 may have a role in targeting selected proteins (e.g., in freshwater
      ionocytes) nonessential for adaptation to seawater for removal via the proteasome
      pathway.

PMID- 12010747
TI  - Pre- and postjunctional alpha(2)-adrenergic receptors in fetal and adult ovine
      cerebral arteries.
AB  - In ovine cerebral arteries, adrenergic-mediated vasoconstrictor responses differ
      significantly with developmental age. We tested the hypothesis that, in part,
      these differences are a consequence of altered alpha(2)-adrenergic receptor
      (alpha(2)-AR) density and/or affinity. In fetal (approximately 140 days) and
      adult sheep, we measured alpha(2)-AR density and affinity with the antagonist
      [(3)H]idazoxan in main branch cerebral arteries and other vessels. We also
      quantified contractile responses in middle cerebral artery (MCA) to
      norepinephrine (NE) or phenylephrine in the presence of the alpha(2)-AR
      antagonists yohimbine and idazoxan and contractile responses to the alpha(2)-AR
      agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates,
      alpha(2)-AR density was 201 +/- 18 and 52 +/- 6 fmol/mg protein, respectively (P
      < 0.01); however, antagonist affinity values did not differ. In fetal, but not
      adult, MCA, 10(-7) M yohimbine significantly decreased the pD(2) for NE-induced
      tension in the presence of 3 x 10(-5) M cocaine, 10(-5) M deoxycorticosterone,
      and 10(-6) M tetrodotoxin. In fetal, but not adult, MCA, UK-14304 induced a
      significant decrease in pD(2) for the phenylephrine dose-response relation. In
      addition, stimulation-evoked fractional NE release was significantly greater in
      fetal than in adult cerebral arteries. In the presence of 10(-6) M idazoxan to
      block alpha(2)-AR-mediated inhibition of prejunctional NE release, the fractional
      NE release was significantly increased in both age groups. We conclude that in
      fetal and adult ovine cerebral arteries, alpha(2)-AR appear to be chiefly
      prejunctional. Nonetheless, the fetal cerebral arteries appear to have a
      significant component of postjunctional alpha(2)-AR.

PMID- 12010748
TI  - Effects of angiotensins on day-night fluctuations and stress-induced changes in
      blood pressure.
AB  - In this study we evaluated by telemetry the effects of ANG II and ANG-(1-7)
      infusion on the circadian rhythms of blood pressure (BP) and heart rate (HR) and
      on the cardiovascular adjustment resulting from restraint stress in rats. ANG II
      or ANG-(1-7) or vehicle were infused subcutaneously for 7 days. Restraint stress
      was carried out before, during, and after infusion at 7-day intervals. Parallel
      with an increase in MAP, ANG II infusion produced an inversion of MAP circadian
      rhythm with a significant MAP acrophase inversion. It also produced bradycardia
      during the first 3 days of infusion. Thereafter, HR progressively increased,
      reaching values similar to or above those of the control period at the end of the
      infusion period. HR circadian variation was not changed by ANG II infusion.
      Strikingly, ANG II significantly attenuated the increase in MAP induced by
      restraint stress without altering the HR response. ANG-(1-7) infusion produced a
      slight but significant decrease in MAP restricted to the daytime period. No
      significant changes in the MAP acrophase were observed. In addition, ANG-(1-7)
      infusion produced a small but significant sustained bradycardia. ANG-(1-7) did
      not change cardiovascular responses to restraint stress. These data indicate that
      ANG II can influence the activity of brain areas involved in the determination of
      stress-induced or circadian-dependent variations of blood pressure without
      changing HR fluctuations. A significant modulatory influence of ANG-(1-7) on
      basal MAP and HR is also suggested.

PMID- 12010749
TI  - Postnatal changes in inhibitory effect of C-type natriuretic peptide on secretion
      of ANP.
AB  - To define developmental changes in atrial natriuretic peptide (ANP) secretion and
      in the cross talk between C-type natriuretic peptide (CNP) and ANP, we performed
      experiments in isolated perfused nonbeating cardiac atria isolated from rabbits
      between 1 and 8 wk of age. Changes in atrial pressure resulted in increases in
      atrial volume that rose with age and reached the peak value at 4 wk. A rise in
      volume change increased ANP secretion with concomitant translocation of
      extracellular fluid (ECF) into the atrial lumen, which increased with age and
      reached the peak value at 4 wk. The positive relationship between stretch-induced
      ANP secretion and ECF translocation shifted upward and leftward with age. CNP
      suppressed stretch-induced ANP secretion in the 8-wk-old group but not in the 2-
      and 4-wk-old groups without differences in ECF translocation and atrial volume.
      Therefore, the ANP secretion in terms of ECF translocation was markedly
      suppressed by CNP in the 8-wk-old group but not in the 2- and 4-wk-old groups.
      The production of cGMP by CNP in atrial tissue membranes was markedly attenuated
      in young rabbits. However, 8-bromo-cGMP suppressed stretch-induced ANP secretion
      in 2- and 8-wk-old groups. Natriuretic peptide receptor-B mRNA was similar in
      both groups. Therefore, we conclude that the inhibitory effect of CNP on atrial
      ANP secretion is developmentally regulated, being absent during normal cardiac
      development in young animals and intact in adult animals.

PMID- 12010750
TI  - Acute stressor exposure facilitates innate immunity more in physically active
      than in sedentary rats.
AB  - Most previous stress-immune research focused on the immunosuppressive effects of
      stress on acquired immunity. More recently, it has become clear that acute
      stressor exposure can potentiate innate, as well as suppress acquired, immunity.
      For example, acute stress improves recovery from bacterial inflammation, a
      classic in vivo measure of innate immunity. The previous work was done in
      sedentary organisms. Physical activity status can modulate the impact of stress
      on immune function. The following studies tested the hypothesis that the effect
      of stress on inflammation after subcutaneous challenge with bacteria (Escherichia
      coli) is facilitated by physical activity. The results were that sedentary,
      stressed rats resolved their inflammation 1-2 days faster and have increased
      circulating neutrophils compared with their nonstressed, sedentary counterparts.
      In contrast, physically active, stressed rats resolve their inflammation 3-4 days
      faster and have increased circulating and inflammatory site neutrophils compared
      with their nonstressed counterparts. Importantly, the beneficial impact of stress
      on inflammation recovery and neutrophil migration was greater in the physically
      active, than sedentary, stressed rats. Thus physical activity status facilitates
      the positive effect of acute stress on innate immunity.

PMID- 12010751
TI  - Contractile properties and myosin expression in rats born and reared in
      hypergravity.
AB  - The effects of hypergravity (HG) on soleus and plantaris muscles were studied in
      Long Evans rats aged 100 days, born and reared in 2-g conditions (HG group). The
      morphological and contractile properties and the myosin heavy chain (MHC) content
      were examined in whole muscles and compared with terrestrial control (Cont) age
      paired rats. The growth of HG rats was slowed compared with Cont rats. A decrease
      in absolute muscle weight was observed. An increase in fiber cross-sectional
      area/muscle wet weight was demonstrated, associated with an increase in relative
      maximal tension. The soleus muscle changed into a slower type both in contractile
      parameters and in MHC content, since HG soleus contained only the MHC I isoform.
      The HG plantaris muscle presented a faster contractile behavior. Moreover, the
      diversity of hybrid fiber types expressing multiple MHC isoforms (including MHC
      IIB and MHC IIX isoforms) was increased in plantaris muscle after HG. Thus the HG
      environment appears as an important inductor of muscular plasticity both in slow
      and fast muscle types.

PMID- 12010752
TI  - Vasodilator responses to adenosine and hyperemia are mediated by A(1) and A(2)
      receptors in the cat vascular bed.
AB  - Hemodynamic responses to adenosine, the A(1) receptor agonists N(6)
      cyclopentyladenosine (CPA) and adenosine amine congener (ADAC), and the A(2)
      receptor agonist 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA) were
      investigated in the hindquarter vascular bed of the cat under constant-flow
      conditions. Injections of adenosine, CPA, ADAC, CPCA, ATP, and adenosine 5'-O-(3
      thiotriphosphate) (ATPgamma S) into the perfusion circuit induced dose-related
      decreases in perfusion pressure. Vasodilator responses to the A(1) agonists were
      reduced by the A(1) receptor antagonists KW-3902 and CGS-15943, whereas responses
      to CPCA were reduced by the A(2) antagonist KF-17837. Vasodilator responses to
      adenosine were reduced by KW-3902, CGS-15943, and by KF-17837, suggesting a role
      for both A(1) and A(2) receptors. Vasodilator responses to ATP and the
      nonhydrolyzable ATP analog ATP gamma S were not attenuated by CGS-15943 or KF
      17837. After treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L
      arginine methyl ester, the cyclooxygenase inhibitor sodium meclofenamate, or the
      ATP-dependent K(+) (K) channel antagonists U-37883A or glibenclamide, responses
      to adenosine and ATP were not altered. Responses to adenosine, CPA, and CPCA were
      increased in duration by rolipram, a type 4 cAMP phosphodiesterase inhibitor, but
      were not altered by zaprinast, a type 5 cGMP phosphodiesterase inhibitor. When
      blood flow was interrupted for a 30-s period, the magnitude and duration of the
      reactive vasodilator response were reduced by A(1) and A(2) receptor antagonists.
      These data suggest that vasodilator responses to adenosine and the A(1) and A(2)
      agonists studied are not dependent on the release of cyclooxygenase products,
      nitric oxide, or the opening of K channels in the regional vascular bed of the
      cat. The present data suggest a role for cAMP in mediating responses to adenosine
      and suggest that vasodilator responses to adenosine and to reactive hyperemia are
      mediated in part by A(1) and A(2) receptors in the hindquarter vascular bed of
      the cat.

PMID- 12010753
TI  - Early osmoregulatory stimulation of neurohypophyseal hormone secretion and thirst
      after gastric NaCl loads.
AB  - Cerebral osmoreceptors mediate thirst and neurohypophyseal secretion stimulated
      by increases in the effective osmolality of plasma (P(osmol)). The present
      experiments determined whether an intragastric load of hypertonic saline (ig HS;
      0.5 M NaCl, 4 ml) would potentiate these responses before induced increases in
      P(osmol) in the general circulation could be detected by cerebral osmoreceptors.
      Adult rats deprived of water overnight and then given intragastric HS consumed
      much more water in 15-30 min than rats given either pretreatment alone, even
      though systemic P(osmol) had not yet increased significantly because of the
      gastric load. In other rats pretreated with an intravenous infusion of 1 M NaCl
      (2 ml/h for 2 h), plasma levels of vasopressin and oxytocin were considerably
      elevated 15 and 25 min after intragastric HS treatment, whereas systemic P(osmol)
      was not increased further. These and other findings are consistent with previous
      reports that hepatic portal osmoreceptors (or Na(+) receptors) stimulate thirst
      and neurohypophyseal hormone secretion in euhydrated rats given gastric NaCl
      loads and indicate that these effects are potentiated when animals are
      dehydrated.

PMID- 12010754
TI  - Arterial baroreceptors mediate the inhibitory effect of acute increases in
      arterial blood pressure on thirst.
AB  - The present study sought to determine whether arterial baroreceptor afferents
      mediate the inhibitory effect of an acute increase in arterial blood pressure
      (AP) on thirst stimulated by systemically administered ANG II or by
      hyperosmolality. Approximately 2 wk after sinoaortic denervation, one of four
      doses of ANG II (10, 40, 100, or 250 ng. kg(-1) x min(-1)) was infused
      intravenously in control and complete sinoaortic-denervated (SAD) rats. Complete
      SAD rats ingested more water than control rats when infused with 40, 100, or 250
      ng x kg(-1) x min(-1) ANG II. Furthermore, complete SAD rats displayed
      significantly shorter latencies to drink compared with control rats. In a
      separate group of rats, drinking behavior was stimulated by increases in plasma
      osmolality, and mean AP was raised by an infusion of phenylephrine (PE). The
      infusion of PE significantly reduced water intake and lengthened the latencies to
      drink in control rats but not in complete SAD rats. In all experiments, drinking
      behavior of rats that were subjected to sinoaortic denervation surgery but had
      residual baroreceptor reflex function (partial SAD rats) was similar to that of
      control rats. Thus it appears that arterial baroreceptor afferents mediate the
      inhibitory effect of an acute increase in AP on thirst stimulated by ANG II or
      hyperosmolality.

PMID- 12010755
TI  - Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired
      cavernosal relaxation with ischemia.
AB  - We examined whether endogenous inhibitors of nitric oxide (NO) synthesis are
      involved in the impaired cavernosal relaxation with ischemia in rabbits. Two
      weeks after cavernosal ischemia caused by partial vessel occlusion, endothelium
      dependent and electrical field stimulation (EFS)-induced neurogenic NO-mediated
      relaxations, but not sodium nitroprusside (SNP)-induced relaxation, were
      significantly impaired in the isolated corpus cavernosum. The Ca(2+)-dependent NO
      synthase (NOS) activity and the basal and stimulated cGMP productions with
      carbachol or EFS were significantly decreased after ischemia. Supplementation of
      excess L-arginine partially recovered both of the impaired relaxations. The
      contents of N(G)-monomethyl-L-arginine (L-NMMA) and asymmetric N(G), N(G)
      dimethyl-L-arginine (ADMA) but not L-arginine and symmetric N(G),N'(G)-dimethyl-L
      arginine (SDMA) were increased in the cavernosal tissues after ischemia.
      Authentic L-NMMA and ADMA but not SDMA concentration dependently inhibited both
      relaxations without affecting the relaxation produced by SNP in the control.
      Excess L-arginine abolished the inhibition with L-NMMA and ADMA. These results
      suggest that the impaired NO-mediated cavernosal relaxations after ischemia are
      closely related to the decreased NOS activity and the increased accumulation of L
      NMMA and ADMA.

PMID- 12010756
TI  - Ribozyme compromise of adrenomedullin mRNA reveals a physiological role in the
      regulation of water intake.
AB  - The adrenomedullin (AM) preprohormone is posttranslationally processed to result
      in two biologically active fragments, AM and proadrenomedullin NH(2)-terminal 20
      peptide (PAMP). AM is thought to play a role in fluid and electrolyte balance by
      acting in brain to inhibit salt and water appetite and in the kidney to cause
      diuresis and natriuresis. We previously have shown that AM is necessary for the
      short-term regulation of salt intake. In this paper, we have designed a ribozyme,
      a catalytic RNA molecule, which specifically recognizes and cleaves the AM
      transcript. In cultured vascular smooth muscle cells, ribozyme treatment lowered
      AM mRNA and reduced peptide content. Intracerebroventricular administration of
      the ribozyme lowered hypothalamic AM content and led to an exaggerated drinking
      response in rats, demonstrating that endogenous, brain-derived AM is
      physiologically relevant and necessary for short-term control of water intake.

PMID- 12010757
TI  - Baroreflex stabilization of the double (pressure-rate) product at 0.05 Hz in
      conscious rabbits.
AB  - The product of heart rate (HR) and systolic blood pressure (SBP), the double
      product (DP), is an indirect index of cardiac oxygen consumption. We used
      spectral analysis to test the hypothesis that baroreflex adjustments of HR
      stabilize the DP during spontaneous variations in SBP. SBP and HR were recorded
      by telemetry in five male conscious rabbits. HR and SBP power spectra each
      exhibited a low frequency peak at approximately 0.05 Hz that was associated with
      high (>0.5) spectral coherence and a positive phase relationship between SBP and
      HR (SBP leading). A prominent peak was absent in the spectra of their product,
      suggesting that SBP and HR interacted to reduce DP variability in this frequency
      region. In contrast, a prominent 0.05-Hz peak was present in the power spectrum
      of calculated surrogates of the DP in which reflex interactions between HR and
      SBP had been removed. Our results suggest that baroreflex adjustments of HR
      stabilize the DP during spontaneous low-frequency variations in SBP in conscious
      rabbits.

PMID- 12010758
TI  - Natriuresis induced by mild hypernatremia in humans.
AB  - The hypothesis that increases in plasma sodium induce natriuresis independently
      of changes in body fluid volume was tested in six slightly dehydrated seated
      subjects on controlled sodium intake (150 mmol/day). NaCl (3.85 mmol/kg) was
      infused intravenously over 90 min as isotonic (Iso) or as hypertonic saline
      (Hyper, 855 mmol/l). After Hyper, plasma sodium increased by 3% (142.0 +/- 0.6 to
      146.2 +/- 0.5 mmol/l). During Iso a small decrease occurred (142.3 +/- 0.6 to
      140.3 +/- 0.7 mmol/l). Iso increased estimates of plasma volume significantly
      more than Hyper. However, renal sodium excretion increased significantly more
      with Hyper (291 +/- 25 vs. 199 +/- 24 micromol/min). This excess was not mediated
      by arterial pressure, which actually decreased slightly. Creatinine clearance did
      not change measurably. Plasma renin activity, ANG II, and aldosterone decreased
      very similarly in Iso and Hyper. Plasma atrial natriuretic peptide remained
      unchanged, whereas plasma vasopressin increased with Hyper (1.4 +/- 0.4 to 3.1 +/
      0.5 pg/ml) and decreased (1.3 +/- 0.4 to 0.6 +/- 0.1 pg/ml) after Iso. In
      conclusion, the natriuretic response to Hyper was 50% larger than to Iso,
      indicating that renal sodium excretion may be determined partly by plasma sodium
      concentration. The mechanism is uncertain but appears independent of changes in
      blood pressure, glomerular filtration rate, the renin system, and atrial
      natriuretic peptide.

PMID- 12010759
TI  - Site-specific modulation of LPS-induced fever and interleukin-1 beta expression
      in rats by interleukin-10.
AB  - Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic
      cytokines such as interleukin (IL)-1 beta. We hypothesized that the anti
      inflammatory cytokine IL-10 modulates the febrile response to LPS by suppressing
      the production of pyrogenic cytokines. In rats, intravenous but not
      intracerebroventricular infusion of IL-10 was found to attenuate fever induced by
      peripheral administration of LPS (10 microg/kg iv). IL-10 also suppressed LPS
      induced IL-1 beta production in peripheral tissues and in the brain stem. In
      contrast, central administration of IL-10 attenuated the febrile response to
      central LPS (60 ng/rat icv) and decreased IL-1 beta production in the
      hypothalamus and brain stem but not in peripheral tissues and plasma.
      Furthermore, intravenous LPS upregulated expression of IL-10 receptor (IL-10R1)
      mRNA in the liver, whereas intracerebroventricular LPS enhanced IL-10R1 mRNA in
      the hypothalamus. We conclude that IL-10 modulates the febrile response by acting
      in the periphery or in the brain dependent on the primary site of inflammation
      and that its mechanism of action most likely involves inhibition of local IL-1
      beta production.

PMID- 12010761
TI  - Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury
      in rats.
AB  - Central neuropeptides play important roles in many physiological and
      pathophysiological regulation mediated through the autonomic nervous system. In
      regard to the hepatobiliary system, several neuropeptides act in the brain to
      regulate bile secretion, hepatic blood flow, and hepatic proliferation. Central
      injection of corticotropin-releasing factor (CRF) aggravates carbon tetrachloride
      (CCl4)-induced acute liver injury through the sympathetic nervous pathway in
      rats. However, still nothing is known about a role of endogenous neuropeptides in
      the brain in hepatic pathophysiological regulations. Involvement of endogenous
      CRF in the brain in CCl4-induced acute liver injury was investigated by centrally
      injecting a CRF receptor antagonist in rats. Male fasted Wistar rats were
      injected with CRF receptor antagonist alpha-helical CRF-(9-41) (0.125-5 microg)
      intracisternally just before and 6 h after CCl4 (2 ml/kg) administration, and
      blood samples were obtained before and 24 h after CCl4 injection for measurement
      of hepatic enzymes. The liver sample was removed 24 h after CCl4 injection, and
      histological changes were examined. Intracisternal alpha-helical CRF-(9-41) dose
      dependently (0.25-2 microg) reduced the elevation of alanine aminotransferase and
      aspartate aminotransferase levels induced by CCl4. Intracisternal alpha-helical
      CRF-(9-41) reduced CCl4-induced liver histological changes, such as centrilobular
      necrosis. The effect of central CRF receptor antagonist on CCl4-induced liver
      injury was abolished by sympathectomy and 6-hydroxydopamine pretreatment but not
      by hepatic branch vagotomy or atropine pretreatment. These findings suggest the
      regulatory role of endogenous CRF in the brain in experimental liver injury in
      rats.

PMID- 12010760
TI  - Neurochemical phenotype of hypothalamic neurons showing Fos expression 23 h after
      intracranial AgRP.
AB  - Agouti-related protein (AgRP) is coexpressed with neuropeptide Y (NPY) in a
      population of neurons in the arcuate nucleus (ARC) of the hypothalamus and
      stimulates food intake for up to 7 days if injected intracerebroventricularly.
      The prolonged food intake stimulation does not seem to depend on continued
      competition at the melanocortin-4 receptor (MC4R), because the relatively
      specific MC4R agonist MTII regains its ability to suppress food intake 24 h after
      AgRP injection. Intracerebroventricular AgRP also stimulates c-Fos expression 24
      h after injection in several brain areas, so the neurons exhibiting delayed Fos
      expression might be particularly important in feeding behavior. Thus we aimed to
      identify the neurochemical phenotype of some of these neurons in select
      hypothalamic areas, using double-label immunohistochemistry. AgRP-injected rats
      ingested significantly more chow (10.2 +/- 0.6 g) vs. saline controls (3.4 +/-
      0.7 g) in the first 9 h (light phase) after injection. In the lateral
      hypothalamus (particularly the perifornical area) 23 h after injection, AgRP
      induced significantly more Fos vs. saline in orexin-A (OXA) neurons (25.6 +/- 4.9
      vs. 4.8 +/- 3.1%), but not in melanin-concentrating hormone (MCH) or cocaine- and
      amphetamine-regulated transcript (CART) neurons. In the ARC, AgRP induced
      significantly more Fos in CART (40.6 +/- 5.9 vs. 13.4 +/- 1.8%) but not NPY
      neurons. In the paraventricular nucleus, there was no significant difference in
      Fos expression induced by AgRP vs. saline in oxytocin and CART neurons. We
      conclude that the long-lasting hyperphagia induced by AgRP is correlated with and
      possibly partially mediated by hyperactive OXA neurons in the lateral
      hypothalamus and CART neurons in the ARC, but not by NPY and MCH neurons. The
      substantial increase in light-phase food intake by AgRP supports a role for the
      arousing effects of OXA. Activation of CART neurons in the ARC (which likely
      coexpress proopiomelanocortin) could indicate attempts to activate
      counterregulatory decreases in food intake.

PMID- 12010762
TI  - Trans-10, cis-12, but not cis-9, trans-11 CLA isomer, inhibits brown adipocyte
      thermogenic capacity.
AB  - Conjugated linoleic acid (CLA) is reported to have health benefits, including
      reduction of body fat. Previous studies have shown that brown adipose tissue
      (BAT) is particularly sensitive to CLA-supplemented diet feeding. Most of them
      use mixtures containing several CLA isomers, mainly cis-9, trans-11 and trans-10,
      cis-12 in equal concentration. Our aim was to characterize the separate effects
      of both CLA isomers on thermogenic capacity in cultured brown adipocytes. The CLA
      isomers showed opposite effects. Hence, on the one hand, trans-10, cis-12
      inhibited uncoupling protein (UCP) 1 induction by norepinephrine (NE) and
      produced a decrease in leptin mRNA levels. These effects were associated with a
      blockage of CCAAT-enhancer-binding protein-alpha and peroxisome proliferator
      activated receptor-gamma(2) mRNA expression. On the other hand, cis-9, trans-11
      enhanced the UCP1 elicited by NE, an effect reported earlier for polyunsaturated
      fatty acids and also observed here for linoleic acid. These findings could
      explain, at least in part, the effects observed in vivo when feeding a CLA
      mixture supplemented diet as a result of the combined action of CLA isomers
      (reduction of adipogenesis and defective BAT thermogenesis that could be through
      trans-10, cis-12 and enhanced UCP1 thermogenic capacity through cis-9, trans-11).

PMID- 12010763
TI  - Quinine and citric acid elicit distinctive Fos-like immunoreactivity in the rat
      nucleus of the solitary tract.
AB  - The present experiment investigated Fos-like immunoreactivity (FLI) in the
      nucleus of the solitary tract (NST) after intraoral infusions of 0.1 M citric
      acid, 0.3 M NaCl, and 0.3-30 mM quinine monohydrochloride (QHCl) in awake,
      behaving rats. Increases in QHCl concentration produced increases in the numbers
      of FLI-labeled neurons in the rostral part of the intermediate (i(r)) and rostral
      (r) NST, but the topographic distribution of FLI was consistent across QHCl
      concentrations and distinctive compared with effects of citric acid. Quinine
      elicited FLI concentrated in the medial third of the nucleus; acid elicited more
      broadly distributed FLI concentrated farther laterally. Surprisingly, in contrast
      to QHCl and citric acid, NaCl produced FLI that was indistinguishable from that
      produced by water. Although the functional significance of these patterns is
      unknown, citric acid and QHCl are nonpreferred stimuli but produced different
      oromotor behaviors. QHCl (30 mM) elicited approximately 3.2 times as many gapes
      as citric acid (0.1 M), and acid elicited more ingestive responses. Parallel
      differences in FLI expression suggest that different NST regions may have
      distinctive roles in triggering oromotor behaviors.

PMID- 12010764
TI  - Agonist-directed trafficking explaining the difference between response pattern
      of naratriptan and sumatriptan in rabbit common carotid artery.
AB  - 1. Sumatriptan or eletriptan produced vasocontraction in common carotid artery
      (CCA) by stimulating 5HT(1B) receptors (see also Akin & Gurdal, this issue). 2.
      Naratriptan as a 5HT(1B/D) agonist, was unable to produce vasocontraction in this
      artery, but inhibited the vasocontractile response induced by sumatriptan or
      eletriptan. 3. All these agonists inhibited forskolin-stimulated cyclic AMP
      production with comparable potencies and maximal responses. This inhibition was
      mediated by 5HT(1B) receptors: 5HT(1B) antagonist SB216641 (1 microM) completeley
      antagonized sumatriptan-, eletriptan- or naratriptan-induced cyclic AMP
      inhibition, but 5HT(1D) antagonist BRL15572 (1 microM) did not affect this
      response. 4. Naratriptan-induced stimulation of 5-HT(1B) receptors resulted only
      in adenylate cyclase inhibition, whereas stimulation of these receptors by
      sumatriptan or eletriptan produced vasocontraction as well. Hence, we concluded
      that the 5HT(1B)-mediated inhibition of adenylate cyclase was not a sufficient
      condition to couple the receptor stimulation to vasocontraction. 5. We discussed
      agonist-induced trafficking as a plausible mechanism for the observed phenomenon.

PMID- 12010765
TI  - Involvement of 5-HT1B and 5-HT1D receptors in sumatriptan mediated
      vasocontractile response in rabbit common carotid artery.
AB  - 1. In this study we examined the involvement of 5-HT(1B) and 5-HT(1D) receptors
      in the vasocontractile response induced by 5-HT(1B/D)-receptor agonist
      sumatriptan in rabbit common carotid artery (CCA). 2. Immunoblotting experiments
      using specific antisera against 5-HT(1B) or 5-HT(1D) receptors revealed the
      presence of one weak (at 93 kD for 5-HT(1B) or at 105 kD for 5-HT(1D)) and one
      strong band (at 46 kD for 5-HT(1B) or at 52 kD for 5-HT(1D)) in CCA. 3.
      Sumatriptan-mediated vasocontractile response was antagonized by SB216641 with an
      apparent pKb value of 8.6, which was consistent with its affinity for 5-HT(1B)
      receptor. Antagonism by BRL15572 was weak and calculated apparent pKb (6.0) value
      was consistent with its affinity for 5-HT(1B) subtype (but not for 5-HT(1D)
      subtype). This result indicates insignificant or no involvement of 5-HT(1D)
      receptor in the vasocontractile response. 4. The vasocontractile response induced
      by sumatriptan was highly sensitive to pertussis toxin treatment of CCA.
      Nicardipine, a calcium channel blocker, also potently antagonized vasocontractile
      response induced by sumatriptan. 5. 5-HT, but not sumatriptan, stimulated
      inositol phosphate accumulation in CCA. 6. These results indicate that
      stimulation of 5-HT(1B) subtype activate a pertussis toxin (PTX) sensitive G
      protein (Go/Gi) and mediate vasocontraction, in which L-type voltage dependent
      calcium channels are involved.

PMID- 12010766
TI  - Effects of benzothiazepines on human neuronal nicotinic receptors expressed in
      Xenopus oocytes.
AB  - 1. We have investigated the effect of diltiazem and its newly synthesized
      derivative (+,-)-trans-3-acetoxy-8-chloro-2,3-dihydro-5[2-diisopropylamine)ethyl]
      2-(4-methoxyphenyl)-1,5-benzothiazepin-4-(5H)-ona hydrochloride (JAC-65) on
      several recombinant human neuronal nicotinic acetylcholine receptors (nAChRs)
      expressed in Xenopus oocytes. 2. At 3 microM, both drugs have little effect on
      the maximal currents evoked by brief pulses of acetylcholine (ACh) in five
      subtypes of nAChRs (alpha7, alpha3beta2, alpha4beta2, alpha3beta4, and
      alpha4beta4), showing little selectivity among subtypes. 3. However, both drugs
      accelerate the decay of the ionic currents evoked upon continuous stimulation of
      ACh, being this effect larger with JAC-65, and in beta4*-nAChRs. Such an effect
      was dependent on the concentrations of both the drug and of the agonist used, and
      showed the characteristics of a non-competitive antagonism. 4. We have further
      investigated the effect of both drugs when combined with submicromolar
      concentrations of nicotine, such as those present in plasma of cigarette smokers,
      and found that JAC-65, but not diltiazem, is able to greatly enhance the
      desensitizing effect of these low concentrations of nicotine, specially in beta4*
      nAChRs. 5. Experiments in alpha4beta4-nAChRs failed to show voltage dependence of
      the action of JAC-65. Moreover, recovery from desensitization followed the same
      time course regardless of the presence of the drug, suggesting that the main
      mechanism of action of JAC-65 does not involve open channel block. 6. In summary,
      both drugs, diltiazem and JAC-65, seem to act through a non-competitive
      mechanism, accelerating the decay of the ionic currents, being JAC-65 more
      effective than diltiazem at the concentrations used in beta4*-nAChRs. Thus, the
      differences between both benzothiazepines when measuring various parameters
      suggest that their mechanisms of action could be slightly different. This would
      require further investigation.

PMID- 12010767
TI  - Carvedilol attenuates neuroleptic-induced orofacial dyskinesia: possible
      antioxidant mechanisms.
AB  - 1. Tardive dyskinesia (TD), a syndrome of potentially irreversible, involuntary
      hyperkinetic disorder occurring in 20 - 40% of the patient population undergoing
      chronic neuroleptic treatment is a major limitation of neuroleptic therapy. 2.
      Oxidative stress and products of lipid peroxidation are implicated in the
      pathophysiology of various neurological disorders including tardive dyskinesia.
      3. Chronic treatment with neuroleptics leads to the development of abnormal oral
      movements in rats known as vacuous chewing movements (VCMs). Vacuous chewing
      movements in rats are widely accepted as an animal model of tardive dyskinesia.
      4. All the antipsychotics were administered i.p. once daily for 21 days, whereas
      carvedilol (also i.p.) was administered twice daily. Rats chronically treated
      with haloperidol (1.0 mg kg(-1)) or chlorpromazine (5 mg kg(-1)) but not
      clozapine (2 mg kg(-1)) significantly developed vacuous chewing movements and
      tongue protrusions. Carvedilol dose dependently (0.5 - 2 mg kg(-1)) reduced the
      haloperidol or chlorpromazine-induced vacuous chewing movements and tongue
      protrusions. 5. Biochemical analysis revealed that chronic haloperidol or
      chlorpromazine but not clozapine treatment significantly induced lipid
      peroxidation and decreased the glutathione (GSH) levels in the forebrains of
      rats. Chronic haloperidol or chlorpromazine but not clozapine treated rats showed
      decreased forebrain levels of antioxidant defence enzymes, superoxide dismutase
      (SOD) and catalase. 6. Co-administration of carvedilol (0.5-2 mg kg(-1))
      significantly reduced the lipid peroxidation and restored the decreased
      glutathione levels by chronic haloperidol or chlorpromazine treatment. Co
      administration of carvedilol (1-2 mg kg(-1)) significantly reversed the
      haloperidol or chlorpromazine-induced decrease in forebrain SOD and catalase
      levels in rats. However, lower dose of carvedilol (0.5 mg kg(-1)) failed to
      reverse chronic haloperidol or chlorpromazine-induced decrease in forebrain SOD
      and catalase levels. 7. The major findings of the present study suggest that
      oxidative stress might play a significant role in neuroleptic-induced orofacial
      dyskinesia. In conclusion, carvedilol could be a useful drug for the treatment of
      neuroleptic-induced orofacial dyskinesia.

PMID- 12010768
TI  - Modification of NMDA responses by tri-n-butyltin in rat brain neurons.
AB  - 1. The effects of the organotin, tri-n-butyltin (TBT), on N-methyl-D-aspartate
      (NMDA) induced membrane currents were investigated in order to evaluate possible
      neuronal actions of this toxic environmental pollutant. Experiments were
      conducted on neurons acutely dissociated from the rat dorsal motor nucleus of
      vagus (DMV) using the nystatin-perforated patch clamp recording technique. 2. In
      Mg(2+)-free physiological recording solutions, the application of NMDA to single
      DMV neurons held at a holding potential (V(H)) of -40 mV evoked an inward current
      which rapidly reached a peak before declining to a steady-state inward current.
      This was followed, immediately after NMDA washout, by a transient outward
      current. TBT (100 nM) reversibly caused a slight reduction in the inward currents
      and greatly increased the amplitude of the outward currents. 3. The reversal
      potential of the NMDA-induced outward current in the presence of TBT was -86.7
      mV, close to the theoretical K(+) equilibrium potential of -85.7 mV. 4. The NMDA
      induced outward current was completely blocked when the K(+) in the internal
      solution was replaced with equimolar Cs(+). Under these conditions, the NMDA
      induced current was more sustained and was unaffected by TBT. 5. The NMDA-induced
      outward current was markedly inhibited by 5 mM tetraethylammonium chloride and
      300 nM charybdotoxin, and it was abolished by removal of extracellular Ca(2+),
      suggesting that the outward current was due to the activation of Ca(2+)-activated
      K(+) channels by Ca(2+) influx through NMDA receptors. 6. In conclusion, in rat
      DMV neurons, TBT potentiates the Ca(2+)-activated K(+) current induced by NMDA
      application without having any direct effects on the NMDA-induced inward current.
      Given the significant role of NMDA receptor mediated excitation in various
      physiological and pathological processes, the modulation of this response by TBT
      may have an important influence on neuronal function.

PMID- 12010769
TI  - Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal
      chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors.
AB  - 1. Tramadol has been used clinically as an analgesic; however, the mechanism of
      its analgesic effects is still unknown. 2. We used bovine adrenal chromaffin
      cells to investigate effects of tramadol on catecholamine secretion, nicotine
      induced cytosolic Ca(2+) concentration ([Ca(2+)](i)) increases and membrane
      current changes. We also investigated effects of tramadol on alpha7 nicotinic
      acetylcholine receptors (AChRs) expressed in Xenopus oocytes. 3. Tramadol
      concentration-dependently suppressed carbachol-induced catecholamine secretion to
      60% and 27% of the control at the concentration of 10 and 100 microM,
      respectively, whereas it had little effect on veratridine- or high K(+)-induced
      catecholamine secretion. 4. Tramadol also suppressed nicotine-induced
      ([Ca(2+)](i)) increases in a concentration-dependent manner. Tramadol inhibited
      nicotine-induced inward currents, and the inhibition was unaffected by the opioid
      receptor antagonist naloxone. 5. Tramadol inhibited nicotinic currents carried by
      alpha7 receptors expressed in Xenopus oocytes. 6. Tramadol inhibited both alpha
      bungarotoxin-sensitive and -insensitive nicotinic currents in bovine adrenal
      chromaffin cells. 7. In conclusion, tramadol inhibits catecholamine secretion
      partly by inhibiting nicotinic AChR functions in a naloxone-insensitive manner
      and alpha7 receptors are one of those inhibited by tramadol.

PMID- 12010770
TI  - Physiological antagonism between ventricular beta 1-adrenoceptors and alpha 1
      adrenoceptors but no evidence for beta 2- and beta 3-adrenoceptor function in
      murine heart.
AB  - 1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We
      investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant
      effects of (-)-adrenaline on spontaneously beating right atria and paced right
      ventricular myocardium of C57BL6 mice. We also studied a negative inotropic
      effect of (-)-adrenaline. 2. Sinoatrial tachycardia, evoked by (-)-adrenaline was
      resistant to blockade by beta(2)-selective ICI 118,551 (50 nM) but antagonized by
      beta(1)-selective CGP 20712A (300 nM). This pattern was unaffected by
      pretreatment with pertussis toxin (PTX, 600 microg kg(-1) i.p. 24 h) which
      reversed carbachol-evoked bradycardia to tachycardia. 3. Increases of ventricular
      force by (-)-adrenaline and (-)-noradrenaline were not blocked by ICI 118,551 but
      antagonized by CGP 20712A. 4. Under blockade of beta-adrenoceptors, (-)
      adrenaline and (-)-noradrenaline depressed ventricular force (-logIC(50)M=7.7 and
      6.9). The cardiodepressant effects of (-)-adrenaline were antagonized by
      phentolamine (1 microM) and prazosin (1 microM) but not by (-)-bupranolol (1
      microM). Prazosin potentiated the positive inotropic effects of (-)-adrenaline
      (in the absence of beta-blockers) from -logEC(50)M=6.2 - 6.8. 5. PTX-treatment
      reduced carbachol-evoked depression of ventricular force in the presence of high
      catecholamine concentrations. Inhibition of ventricular function of G(i) protein
      was verified by 82% reduction of in vitro ADP-ribosylation. PTX-treatment tended
      to increase the positive inotropic potency of (-)-adrenaline under all conditions
      investigated, including the presence of ICI 118,551. 6. (-)-Adrenaline causes
      murine cardiostimulation through beta(1)-adrenoceptors but not through beta(2)
      adrenoceptors. The negative inotropic effects of (-)-adrenaline are mediated
      through ventricular alpha(1)-adrenoceptors but not through beta(3)-adrenoceptors.
      Both G(i) protein and alpha(1)-adrenoceptors restrain (-)-adrenaline-evoked
      increases in right ventricular force mediated through beta(1)-adrenoceptors.

PMID- 12010771
TI  - Release inhibitory receptors activation favours the A2A-adenosine receptor
      mediated facilitation of noradrenaline release in isolated rat tail artery.
AB  - 1. Interactions between A(2A)-adenosine receptors and alpha(2)-, A(1)- and P2-
      release-inhibitory receptors, on the modulation of noradrenaline release were
      studied in isolated rat tail artery. Preparations were labelled with [(3)H]
      noradrenaline, superfused with desipramine-containing medium, and stimulated
      electrically (100 pulses at 5 Hz or 20 pulses at 50 Hz). 2. Blockade of alpha(2)
      autoreceptors with yohimbine (1 microM) increased tritium overflow elicited by
      100 pulses at 5 Hz but not by 20 pulses at 50 Hz. 3. The selective A(2A)-receptor
      agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS
      21680; 1-100 nM) enhanced tritium overflow elicited by 100 pulses at 5 Hz.
      Yohimbine prevented the effect of CGS 21680, which was restored by the A(1)
      receptor agonist N(6)-cyclopentyladenosine (CPA; 100 nM) or by the P2-receptor
      agonist 2-methylthioadenosine triphosphate (2-MeSATP; 80 microM). 4. CGS 21680
      (100 nM) failed to increase tritium overflow elicited by 20 pulses at 50 Hz. The
      alpha(2)-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK
      14304; 30 nM), the A(1)-receptor agonist CPA (100 nM) or the P2-receptor agonist
      2-MeSATP (80 microM) reduced tritium overflow. In the presence of these agonists
      CGS 21680 elicited a facilitation of tritium overflow. 5. Blockade of potassium
      channels with tetraethylammonium (TEA; 5 mM) increased tritium overflow elicited
      by 100 pulses at 5 Hz to values similar to those obtained in the presence of
      yohimbine but did not prevent the effect of CGS 21680 (100 nM) on tritium
      overflow. 6. It is concluded that, in isolated rat tail artery, the facilitation
      of noradrenaline release mediated by A(2A)-adenosine receptors is favoured by
      activation of release inhibitory receptors.

PMID- 12010773
TI  - Interaction of group I mGlu and NMDA receptor agonists within the dorsal horn of
      the spinal cord of the juvenile rat.
AB  - 1. The modulatory effects of mGlu receptors on NMDA-induced potential changes in
      spinal motoneurones were studied in vitro. 2. Selective activation of mGlu5
      receptors by 10 microM (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG; EC(50)=280 +/-
      24 microM) did not produce any change in the ventral root potential. However, the
      same concentration of CHPG (10 min perfusion) significantly attenuated the NMDA
      induced ventral root depolarization (VRD). The effect persisted for 10 min after
      washout. NMDA-induced responses returned to control in 30 min. Brief co
      application of CHPG and NMDA did not alter the NMDA-induced response indicating
      lack of direct receptor interaction. 3. The attenuating effect of CHPG on the
      NMDA-induced VRD was inhibited by the mGluR5 receptor antagonist, 2-methyl-6
      phenyl-ethynylpyridine (MPEP). 4. In the presence of CGP56433A, a GABA(B)
      receptor antagonist, the NMDA-induced VRD was unchanged. However, NMDA-induced
      responses were potentiated after 10 min co-application of CHPG and CGP56433A. 5.
      (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group II mGlu
      receptor agonist did not attenuate the NMDA-induced response. 6. Under normal
      physiological conditions group I mGlu receptor agonists activate at least two
      populations of neurones: (1) GABA-ergic cells, which could release GABA and
      inhibit dorsal horn neurones, and (2) deep dorsal horn neurones/motoneurones
      which express NMDA receptors. Therefore, activation of mGlu5 receptors located on
      GABA-ergic interneurones could influence any direct potentiating interaction
      between mGlu5 and NMDA receptors in spinal cord and result in depression of the
      VRD. In the presence of a GABA(B) receptor antagonist, the direct synergistic
      interaction is unmasked. These data suggest that group I mGlu receptors provide a
      complex modulation of spinal synaptic processes.

PMID- 12010772
TI  - Intracisternal urocortin inhibits vagally stimulated gastric motility in rats:
      role of CRF(2).
AB  - 1. Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin
      releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric
      motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn)
      injected intracisternally (ic) on gastric motor function. 2. Urethane
      anaesthetized rats with strain gauges on the gastric corpus were injected i.c.
      with rUcn and 20 min later, with i.c. RX-77368. CRF antagonists were injected
      i.c. 10 min before rUcn. 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose
      dependently increased corpus contractions, expressed as total area under the
      curve (AUC, mV min(-1)) to 2.6+/-2.5, 6.1+/-5.9, 9.8+/-2.6, 69.7+/-21.7 and
      74.9+/-28.7 respectively vs 0.2+/-0.1 after i.c. saline. Ucn (1, 3 or 10 microg)
      inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93%
      respectively vs i.c. saline+RX-77368. 4. The CRF(1)/CRF(2) antagonist, astressin
      B (60 microg, i.c.) completely blocked i.c. rUcn (3 microg, i.c.)-induced
      inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective
      CRF(2) antagonist, astressin(2)-B (30, 60 or 100 microg, i.c. ) dose-dependently
      prevented i.c. rUCn action while the CRF(1) antagonist, NBI-27914 did not. 6. In
      conscious rats, rUcn (0.6 or 1 microg, i.c.) inhibited gastric emptying of an
      ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by
      astressin(2)-B. 7. These data show that i.c. rUcn acts through CRF(2) receptors
      to inhibit central vagal gastric contractile response and postoprandial emptying.

PMID- 12010774
TI  - Cellular basis of endothelial dysfunction in small mesenteric arteries from
      spontaneously diabetic (db/db -/-) mice: role of decreased tetrahydrobiopterin
      bioavailability.
AB  - 1. Endothelium-dependent and -independent regulation of vascular tone in small
      mesenteric arteries (SMA) from control (db/db +/?) and diabetic (db/db -/-) mice
      was compared. 2. Phenylephrine-induced maximum contraction, but not sensitivity,
      of SMA in db/db -/- compared to db/db +/? was enhanced. 3. Acetylcholine (ACh),
      but not sodium nitroprusside (SNP), -induced relaxation was reduced in SMA from
      db/db -/- compared to db/db +/?. 4. ACh-induced relaxation of SMA was inhibited
      by a combination of N(omega)-nitro-L-arginine and indomethacin in db/db +/?, but
      not in db/db -/-. 5. Acute incubation of SMA with tetrahydrobiopterin (BH(4), 10
      microM) and sepiapterin (100 microM) enhanced ACh-induced relaxation in SMA from
      db/db -/-, but not from db/db +/? 2,4-diamino-6-hydroxypyrimidine, an inhibitor
      of GTP cyclohydrolase I, (10 mM), impaired the sensitivity of SMA from db/db +/?
      to ACh, which was restored by co-incubation with BH(4) (10 microM). 6. BH(4) and
      superoxide dismutase (SOD, 150 u ml(-1)), either alone or in combination, had no
      effect on either ACh or SNP-induced relaxation in SMA from eNOS -/- mice. 7.
      Incubation of SMA with SOD (150 iu ml(-1)), catalase (200 iu ml(-1)) and L
      arginine (1 mM) had no effect on ACh-induced relaxation of SMA. However, the
      combination of polyethylene glycol-SOD (200 iu ml(-1)) and catalase (80 u ml(-1))
      improved the sensitivity of ACh-induced relaxation in db/db -/-, but not in db/db
      +/?. 8. These data suggest that increased production of superoxide anions and
      decreased availability of BH(4) result in an 'uncoupling' of nitric oxide
      synthase and endothelial dysfunction in SMA from db/db -/- mice.

PMID- 12010775
TI  - Reduced coronary vasodilator responses to amlodipine in pacing-induced heart
      failure in conscious dogs: role of nitric oxide.
AB  - 1. This study examined whether NO is involved in the in-vivo coronary vasodilator
      effects of amlodipine (a calcium channel blocker) and whether heart failure (HF)
      alters the coronary responses to amlodipine. 2. Nine conscious dogs were
      chronically instrumented to measure circumflex coronary blood flow (CBF) and
      coronary diameter (CD). Drugs were administered directly into the circumflex
      artery through an indwelling catheter to avoid systemic changes. HF was induced
      by right ventricular pacing (240 b.p.m., 3 weeks). 3. Compared with control (C),
      in HF, coronary responses to acetylcholine (1 - 10 ng kg(-1)) were reduced while
      responses to nitroglycerin (0.1 - 0.5 microg kg(-1)) were unchanged. In C,
      amlodipine (30 - 150 microg kg(-1)), increased dose-dependently CBF and CD. After
      LNA (a NO synthase inhibitor, 2 mg kg(-1)), amlodipine produced less increases in
      CBF and CD (+121+/-26 ml min(-1) and +76+/-35 microm versus +196+/-40 ml min(-1)
      and +153+/-39 microm respectively for 150 microg kg(-1) amlodipine alone, both
      P<0.05). In HF, the coronary responses to amlodipine were reduced (150 microg kg(
      1) of amlodipine increased CBF and CD +121+/-23 ml min(-1) and +77+/-21 microm
      respectively, both P<0.05). After LNA, the CBF responses to amlodipine tended to
      be reduced (+94+/-19 ml min(-1) at 150 microg kg(-1)) but CD responses were
      significantly reduced (+41+/-16 microm, P<0.05). The supplementation with L
      arginine did not enhance the coronary responses to amlodipine. 4. These results
      indicate that, in conscious dogs, NO participates in the coronary responses to
      amlodipine and in HF, the coronary responses to amlodipine are reduced, which is
      related to a reduced NO production.

PMID- 12010776
TI  - Protective effects of neurokinin-1 receptor during colitis in mice: role of the
      epidermal growth factor receptor.
AB  - 1. The role of substance P and its high affinity neurokinin-1 receptor in colitis
      has not been fully elucidated. We assessed the participation of neurokinin-1
      receptor in colitis using the 2,4,6,-trinitrobenzensulphonic acid and dextran
      sulphate-induced animal models of colitis and genetically-engineered, neurokinin
      1 receptor-deficient mice. 2. Clinical signs, macroscopic and histologic damage
      associated with 2,4,6,-trinitrobenzensulphonic acid (12 days) and dextran
      sulphate (5 days) colitis were more severe in neurokinin-1 deficient than in wild
      type mice, while immunoreactivities for epidermal growth factor and its receptor
      were similar in the colon of both mice strains before and after colitis. 3.
      Substance P, dose-dependently induced intestinal fibroblast proliferation and
      enhanced epidermal growth factor-induced proliferation in intestinal fibroblasts
      isolated from wild-type, but not from neurokinin-1 receptor deficient mice. 4.
      Substance P-induced intestinal fibroblast proliferation required the presence of
      epidermal growth factor receptor with kinase activity. Furthermore, substance P
      induced epidermal growth factor tyrosine phosphorylation and activation in normal
      intestinal fibroblasts. 5. Our results indicate that in mice lacking the
      neurokinin - 1 receptor, substance P plays a protective role in prolonged
      experimental colitis.

PMID- 12010777
TI  - Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in
      Caco-2 cells: comparison with the potent histone deacetylase inhibitor
      trichostatin A.
AB  - 1. Medium-chain triglyceride (MCT) is often administered to patients with Crohn's
      disease (CD) or short-bowel syndrome. However, little is known about the effects
      of medium-chain fatty acids (MCFAs) and MCT on intestinal inflammation. In this
      study we examined whether caprylic acid, one of the MCFAs, and MCT suppress IL-8
      secretion by differentiated Caco-2 cells. 2. We found for the first time that
      caprylic acid and MCT suppress IL-8 secretion by Caco-2 cells at the
      transcriptional level when precultured together for 24 h. We also tried to
      clarify the mechanism of IL-8 gene inhibition by examining the activation of NF
      kappaB and other transcription factors by electrophoretic mobility shift assay
      (EMSA), and found that caprylic acid did not modulate their activation. 3. The
      result of dual-luciferase assay using Caco-2 cells transfected with IL-8
      promoter/luciferase reporter plasmid revealed that caprylic acid inhibited the
      activation of IL-8 promoter. 4. Similar results were observed when cells were
      precultured with the well-known potent histone deacetylase inhibitor trichostatin
      A (TSA). 5. We examined the state of H4 acetylation in IL-8 promoter using the
      technique known as chromatin immunoprecipitation (Chr-IP). TSA rapidly induced H4
      acetylation in IL-8 promoter chromatin, whereas caprylic acid did not. These
      results suggest that the inhibition of IL-8 gene transcription induced by
      caprylic acid and TSA does not necessarily require the marked suppression of
      transcription factors, and the mechanism of inhibition of IL-8 gene transcription
      may be different between caprylic acid and TSA.

PMID- 12010778
TI  - Regulation by PGE2 of the production of interleukin-6, macrophage colony
      stimulating factor, and vascular endothelial growth factor in human synovial
      fibroblasts.
AB  - 1. We examined the effects of endogenous prostaglandin E(2) (PGE(2)) on the
      production of interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF),
      and vascular endothelial growth factor (VEGF) by interleukin-1beta (IL-1beta)
      stimulated human synovial fibroblasts. 2. NS-398 (1 microM), a cyclo-oxygenase-2
      (COX-2) inhibitor, inhibited IL-6 and VEGF production (35+/-4% and 26+/-2%,
      respectively) but enhanced M-CSF production (38+/-4%) by IL-1beta (1 ng ml(-1))
      in synovial fibroblasts isolated from patients with osteoarthritis (OA) and
      rheumatoid arthritis (RA). Exogenous PGE(2) completely abolished the effects of
      NS-398 on the production of each mediator by OA fibroblasts stimulated with IL
      1beta. 3. 8-Bromo cyclic AMP and dibutyryl cyclic AMP, cyclic AMP analogues,
      mimicked the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA
      fibroblasts. 4. The EP(2) selective receptor agonist ONO-AE1-259 (2 nM) and the
      EP(4) selective receptor agonist ONO-AE1-329 (2 or 20 nM), but not the EP(1)
      selective receptor agonist ONO-DI-004 (1 microM) and the EP(3) selective receptor
      agonist ONO-AE-248 (1 microM), replaced the effects of PGE(2) on IL-6, M-CSF, and
      VEGF production by OA and RA fibroblasts stimulated with IL-1beta in the presence
      of NS-398. 5. Both OA and RA fibroblasts expressed mRNA encoding EP(2) and EP(4)
      but not EP(1) receptors. In addition, up-regulation of EP(2) and EP(4) receptor
      mRNAs was observed at 3 h after IL-1beta treatment. 6. These results suggest that
      endogenous PGE(2) regulates the production of IL-6, M-CSF, and VEGF by IL-1beta
      stimulated human synovial fibroblasts through the activation of EP(2) and EP(4)
      receptors with increase in cyclic AMP.

PMID- 12010779
TI  - Presynaptic adenosine A2A receptors enhance GABAergic synaptic transmission via a
      cyclic AMP dependent mechanism in the rat globus pallidus.
AB  - 1. We previously reported a presynaptic facilitatory action of A(2A) receptors on
      GABAergic synaptic transmission in the rat globus pallidus (GP). In the present
      study we identify the intracellular signalling mechanisms responsible for this
      facilitatory action of A(2A) receptors, using biochemical and patch-clamp methods
      in rat GP slices. 2. The adenosine A(2A) receptor selective agonist CGS21680 (1,
      10 microM) and the adenylyl cyclase activator forskolin (1, 10 microM) both
      significantly increased cyclic AMP accumulation in GP slices. The CGS21680 (1
      microM)-mediated increase in cyclic AMP was inhibited by the A(2A) receptor
      selective antagonist KF17837 (10 microM). 3. In an analysis of miniature
      inhibitory postsynaptic currents (mIPSCs), forskolin (10 microM) increased the
      mIPSC frequency without affecting their amplitude distribution, a result similar
      to that previously reported with CGS21680. 4. The adenylyl cyclase inhibitor 9
      (tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22,536, 300 microM) abolished the
      CGS21680-induced enhancement in the frequency of mIPSCs. 5. H-89 (10 microM), a
      selective inhibitor for cyclic AMP-dependent protein kinase (PKA), blocked the
      CGS21680-induced enhancement of the mIPSC frequency. 6. The calcium channel
      blocker CdCl(2) (100 microM) did not prevent CGS21680 from increasing the
      frequency of mIPSCs. 7. These results indicate that A(2A) receptor-mediated
      potentiation of mIPSCs in the GP involves the sequential activation of the A(2A)
      receptor, adenylyl cyclase, and then PKA, and that this facilitatory modulation
      could occur independently of presynaptic Ca(2+) influx.

PMID- 12010780
TI  - [Nphe1,Arg14,Lys15]nociceptin-NH2, a novel potent and selective antagonist of the
      nociceptin/orphanin FQ receptor.
AB  - 1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by
      activating a specific G-protein coupled receptor (NOP). Few molecules are
      available that selectively activate or block the NOP receptor. Here we describe
      the in vitro and in vivo pharmacological profile of a novel NOP receptor ligand,
      [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101). 2. UFP-101 binds to the human
      recombinant NOP receptor expressed in Chinese hamster ovary (CHO) cells with high
      affinity (pK(i) 10.2) and shows more than 3000 fold selectivity over classical
      opioid receptors. UFP-101 competitively antagonizes the effects of N/OFQ on
      GTPgamma(35)S binding in CHO(hNOP) cell membranes (pA(2) 9.1) and on cyclic AMP
      accumulation in CHO(hNOP) cells (pA(2) 7.1), being per se inactive at
      concentrations up to 10 microM. 3. In isolated peripheral tissues of mice, rats
      and guinea-pigs, and in rat cerebral cortex synaptosomes preloaded with [(3)H]-5
      HT, UFP-101 competitively antagonized the effects of N/OFQ with pA(2) values in
      the range of 7.3 - 7.7. In the same preparations, the peptide was inactive alone
      and did not modify the effects of classical opioid receptor agonists. 4. UFP-101
      is also active in vivo where it prevented the depressant action on locomotor
      activity and the pronociceptive effect induced by 1 nmol N/OFQ i.c.v. in the
      mouse. In the tail withdrawal assay, UFP-101 at 10 nmol produces per se a robust
      and long lasting antinociceptive effect. 5. UFP-101 is a novel, potent and
      selective NOP receptor antagonist which appears to be a useful tool for future
      investigations of the N/OFQ-NOP receptor system.

PMID- 12010781
TI  - IL-1 beta signalling in glial cells in wildtype and IL-1RI deficient mice.
AB  - 1. Interleukin-1 (IL-1) has been implicated in neurodegeneration and in central
      nervous system (CNS)-mediated host defence responses to inflammation. All actions
      of IL-1 identified to date appear to be mediated through its only known
      functional type I receptor (IL-1RI). However, our recent evidence suggests that
      some actions of IL-1 in the brain may be IL-1RI independent, suggesting the
      involvement of a new, hitherto unknown functional receptor for IL-1. 2. The
      objective of the present study was to determine if primary mixed glial cells
      express additional functional IL-1 receptors by studying the signalling
      mechanisms responsible for the pro-inflammatory actions of IL-1beta in cultures
      derived from IL-1RI-/- and wildtype mice, and to characterize the functional
      importance of IL-1 signalling pathways in glia. 3. IL-1beta induced marked
      release of IL-6 and prostaglandin-E(2) (PGE(2)) in the culture medium, and
      activated nuclear factor-kappa B (NFkappaB) and the mitogen-activated protein
      kinases (MAPK) p38, c-Jun N-terminal kinase (JNK) and the extracellular signal
      regulated protein kinase (ERK1/2) in cells from wildtype mice. These responses
      were dependent on IL-1RI, since cells isolated from IL-1R1-/- mice did not
      demonstrate any of these responses. 4. In wildtype mice, inhibition of p38 or
      ERK1/2 MAPKs significantly reduced IL-1beta induced IL-6 release, whilst the
      NFkappaB inhibitor caffeic acid phenethyl ester (CAPE) modulated IL-1 induced IL
      6 release by action on NFkappaB and MAPKs pathways. 5. These data demonstrate
      that IL-1RI is essential for IL-1beta signalling in cultured mixed glial cells.
      Thus IL-1 actions observed in IL-1RI-/- mice in vivo may occur via an alternative
      pathway and/or via different CNS cells.

PMID- 12010782
TI  - Pharmacological characterization of the 5-HT receptors mediating contraction and
      relaxation of canine isolated proximal stomach smooth muscle.
AB  - 1. We aimed to characterize 5-HT receptors mediating contraction and relaxation
      to 5-HT in dog proximal stomach longitudinal muscle (LM) strips. 2. Of the
      tryptamine analogues tested, 5-HT was the most potent contractile agent at basal
      length, while 5-CT was the most potent relaxant of PGF(2alpha)-induced
      contraction. Neither the contractions to 5-HT, nor the relaxations to 5-CT were
      influenced by tetrodotoxin, illustrating that action potential propagation is not
      involved. 3. The 5-HT-induced contraction was antagonized by mesulergine (0.03 to
      0.3 microM) and ketanserin (2 - 20 nM), but the antagonism was not of a simple
      competitive nature, indicating multiple receptor involvement. Ketanserin (3 to 30
      nM) and mesulergine (30 nM) competitively antagonized the alpha-Me-5-HT-induced
      contraction (pK(B): 8.83+/-0.09 and pA(2): 8.25+/-0.06 respectively). These
      affinity values are in line with literature affinities of ketanserin and
      mesulergine at 5-HT(2A) receptors in various bioassays. 4. The 5-CT-induced
      inhibition of PGF(2alpha)-induced contraction was competitively antagonized by
      mesulergine (pK(B) estimate: 8.52+/-0.12) and by the selective 5-HT(7) receptor
      antagonist SB-269970 (pK(B) estimate: 9.36+/-0.14). Both pK(B) estimates are in
      line with literature affinities of these compounds for 5-HT(7) receptors.
      Mesulergine (30 nM) and SB-269970 (10 nM) shifted the relaxant curve to 5-HT
      parallel to the right in the presence of ketanserin (0.3 microM) (pA(2) estimates
      of 8.08+/-0.10 and 8.75+/-0.14 respectively), indicative of 5-HT(7) receptor
      involvement. 5. It is concluded that 5-HT induces dog proximal stomach (LM)
      contraction via smooth muscle 5-HT(2A) receptors and relaxation via smooth muscle
      5-HT(7) receptors.

PMID- 12010783
TI  - Effects of thymol on calcium and potassium currents in canine and human
      ventricular cardiomyocytes.
AB  - 1. Concentration-dependent effects of thymol (1 - 1000 microM) was studied on
      action potential configuration and ionic currents in isolated canine ventricular
      cardiomyocytes using conventional microelectrode and patch clamp techniques. 2.
      Low concentration of thymol (10 microM) removed the notch of the action
      potential, whereas high concentrations (100 microM or higher) caused an
      additional shortening of action potential duration accompanied by progressive
      depression of plateau and reduction of V(max). 3. In the canine cells L-type Ca
      current (I(Ca)) was decreased by thymol in a concentration-dependent manner
      (EC(50): 158+/-7 microM, Hill coeff.: 2.96+/-0.43). In addition, thymol (50 - 250
      microM) accelerated the inactivation of I(Ca), increased the time constant of
      recovery from inactivation, shifted the steady-state inactivation curve of I(Ca)
      leftwards, but voltage dependence of activation remained unaltered. Qualitatively
      similar results were obtained with thymol in ventricular myocytes isolated from
      healthy human hearts. 4. Thymol displayed concentration-dependent suppressive
      effects on potassium currents: the transient outward current, I(to) (EC(50):
      60.6+/-11.4 microM, Hill coeff.: 1.03+/-0.11), the rapid component of the delayed
      rectifier, I(Kr) (EC(50): 63.4+/-6.1 microM, Hill coeff.: 1.29+/-0.15), and the
      slow component of the delayed rectifier, I(Ks) (EC(50): 202+/-11 microM, Hill
      coeff.: 0.72+/-0.14), however, K channel kinetics were not much altered by
      thymol. These effects on Ca and K currents developed rapidly (within 0.5 min) and
      were readily reversible. 5. In conclusion, thymol suppressed cardiac ionic
      channels in a concentration-dependent manner, however, both drug-sensitivities as
      well as the mechanism of action seems to be different when blocking calcium and
      potassium channels.

PMID- 12010785
TI  - A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro
      and in vivo.
AB  - Constitutively activating internal tandem duplication (ITD) and point mutations
      of the receptor tyrosine kinase FLT3 are present in up to 41% of patients with
      acute myeloid leukemia (AML). These FLT3/ITD mutations are likely to be important
      because their presence is associated with a poor prognosis. Both types of
      mutations appear to activate the tyrosine kinase activity of FLT3. We describe
      here the identification and characterization of the indolocarbazole derivative
      CEP-701 as a FLT3 inhibitor. This drug potently and selectively inhibits
      autophosphorylation of wild-type and constitutively activated mutant FLT3 in
      vitro in FLT3/ITD-transfected cells and in human FLT3-expressing myeloid leukemia
      derived cell lines. We demonstrate that CEP-701 induces a cytotoxic effect on
      cells in a dose-responsive fashion that parallels the inhibition of FLT3. STAT5
      and ERK1/2, downstream targets of FLT3 in the signaling pathway, are inhibited in
      response to FLT3 inhibition. In primary leukemia blasts from AML patients
      harboring FLT3/ITD mutations, FLT3 is also inhibited, with an associated
      cytotoxic response. Finally, using a mouse model of FLT3/ITD leukemia, we
      demonstrate that the drug inhibits FLT3 phosphorylation in vivo and prolongs
      survival. These findings form the basis for a planned clinical trial of CEP-701
      in patients with AML harboring FLT3- activating mutations.

PMID- 12010786
TI  - Interleukin-7: from bench to clinic.

PMID- 12010787
TI  - Maintenance of elevated fetal hemoglobin levels by decitabine during dose
      interval treatment of sickle cell anemia.
AB  - We have previously demonstrated that 5-aza-2'-deoxycytidine (decitabine) augments
      fetal hemoglobin (HbF) levels in patients with sickle cell anemia (SS) who did
      not respond to hydroxyurea (HU). The present study was designed to determine the
      effect of repeated decitabine dosing on HbF levels and hematologic toxicity over
      a 9-month treatment period. Seven patients (5 HU nonresponders) were entered. One
      patient had alpha-thalassemia sickle cell anemia. Decitabine was administered by
      intravenous infusion at a starting dose of 0.3 mg/kg per day, 5 days a week for 2
      weeks, followed by a 4-week observation period. If the absolute neutrophil count
      dropped below 1000, the dose was reduced by 0.05 mg/kg per day in the next cycle.
      A drug dose was obtained for each patient, and it resulted in an elevated HbF
      without neutropenia (absolute neutrophil count nadir greater than 1500) or
      evidence of cumulative toxicity. Average HbF and average maximal HbF levels
      attained during the last 20 weeks of treatment for the 6 SS patients increased to
      13.93% +/- 2.75% and 18.35% +/- 4.46%, respectively, from a pretreatment mean of
      3.12% +/- 2.75%. Mean and mean maximal hemoglobin (Hb) levels increased from 7.23
      +/- 2.35 g/dL to 8.81 +/- 0.42 g/dL and 9.73 +/- 0.53 g/dL, respectively.
      Individual maximal F-cell number observed during the trial was 69% +/- 10.12%.
      The absence of cumulative toxicity may allow shorter intervals between drug
      treatments, which may lead to higher hemoglobin and HbF levels after several
      treatment cycles and, therefore, to greater clinical improvement.

PMID- 12010788
TI  - Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year
      prospective study in France.
AB  - A national prospective study was designed to collect all cases of lymphoma
      appearing in patients with rheumatoid arthritis (RA) treated with methotrexate
      (MTX) throughout France over a period of 3 years. A total of 25 cases of lymphoma
      were recorded, 18 cases of non-Hodgkin lymphoma (NHL), 3 of which were associated
      with the presence of Epstein-Barr virus (EBV) in lymphoma cells, and 7 cases of
      Hodgkin disease (HD), 5 of them associated with EBV. Among the 8 patients who
      were treated by MTX withdrawal alone, 3 underwent remission, but 2 of them had a
      relapse, the third patient with clonal EBV-associated large granular lymphocytes
      T-cell NHL remaining alive in complete remission. The estimated annual incidence
      rate of NHL in RA patients treated with MTX was 33.3.10(-5) (0-80.5) among men
      and 16.7.10(-5) (0-33.3) among women. There was no significant excess with the
      French population as a comparison: the standardized mortality ratio (SMR)
      adjusted for age and sex was 1.07 (0.6-1.7). The estimated annual incidence rate
      of HD among men and women was, respectively, 27.8.10(-5) (0-70.1) and 2.8.10(-5)
      (0- 9.6). The incidence of HD was significantly increased compared with the
      French incidence, with an SMR adjusted for age and sex of 7.4 (3.0-15.3; P
      <.001). Thus, this 3-year prospective study indicated that, whereas the risk of
      NHL was not significantly increased in RA patients treated with MTX, the
      incidence of HD appeared to be higher in these patients compared to the French
      population.

PMID- 12010789
TI  - Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV
      infection not responding to antiviral chemotherapy.
AB  - We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell
      lines into 8 stem cell transplant recipients lacking CMV-specific T-cell
      proliferation. All patients, of whom one was infected by a CMV strain that was
      genotypically ganciclovir resistant, had received unsuccessful antiviral
      chemotherapy for more than 4 weeks. CMV-specific lines had been prepared by
      repetitive stimulation with CMV antigen, which increased the percentage of CMV
      specific T cells and ablated alloreactivity completely even against patients
      mismatched for 1 to 3 HLA antigens. After transfer of 10(7) T cells/m(2) at a
      median of 120 days (range, 79-479 days) after transplantation, no side effects
      were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped
      significantly in all 7 evaluable patients, with a maximal reduction after a
      median of 20 days (range, 5-31 days). In 2 patients with high virus load, the
      antiviral effect was only transient. One of these patients received a second T
      cell infusion, which cleared the virus completely. At a median of 11 days after
      transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and
      an increase in CMV-specific CD4(+) T cells was demonstrated in 5 patients. In 6
      patients, 1.12 to 41 CMV-specific CD8(+) T cells/microL blood were detected at a
      median of 13 days after transfer, with an increase in all patients lacking CMV
      specific CD8(+) T cells prior to transfer. Hence, anti-CMV cellular therapy was
      successful in 5 of 7 patients, whereas in 2 of 7 patients, who received an
      intensified immune suppression at the time of or after T-cell therapy, only
      transient reductions in virus load were obtained.

PMID- 12010790
TI  - A new adenoviral helper-dependent vector results in long-term therapeutic levels
      of human coagulation factor IX at low doses in vivo.
AB  - We have developed a new helper-dependent (HD) adenoviral vector FTC that contains
      3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA,
      matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To
      determine the most robust human coagulation factor IX (hFIX) expression cassette
      in an adenovirus, we first tested different hFIX expression sequences with or
      without flanking MARs in first-generation adenoviral vectors. After intravenous
      infusion of the vector, serum levels of up to 100 000 ng/mL hFIX (normal level,
      5000 ng/mL) were obtained at nontoxic doses. In order to make a direct
      comparison, a first-generation and a gene-deleted vector with identical hFIX
      expression cassettes were constructed. Both first-generation and HD adenovirus
      treated animals demonstrated a threshold effect in a dose-response study. With
      the administration of 2 x 10(9) transducing particles of either vector,
      supraphysiological serum levels of hFIX were obtained, with the highest
      expression (41 000 ng/mL) occurring during the first 2 months after injection.
      The serum factor IX concentrations, while remaining in the therapeutic range,
      slowly declined by 95% over a period of 1 year. At this dose, interleukin-6 and
      tumor necrosis factor-alpha serum concentrations were elevated in animals that
      received the first-generation but not the HD vector. This study compares the
      properties of a gene-deleted and first-generation adenovirus with equivalent
      expression cassettes and suggests that the cis-DNA elements contained in the
      vector and expression cassette have important effects on gene expression in vivo.

PMID- 12010791
TI  - Rescue of the lethal scl(-/-) phenotype by the human SCL locus.
AB  - The stem cell leukemia (SCL) gene encodes a basic helix-loop-helix transcription
      factor with a critical role in the development of both blood and endothelium.
      Loss-of-function studies have shown that SCL is essential for the formation of
      hematopoietic stem cells, for subsequent erythroid development and for yolk sac
      angiogenesis. SCL exhibits a highly conserved pattern of expression from mammals
      to teleost fish. Several murine SCL enhancers have been identified, each of which
      directs reporter gene expression in vivo to a subdomain of the normal SCL
      expression pattern. However, regulatory elements necessary for SCL expression in
      erythroid cells remain to be identified and the size of the chromosomal domain
      needed to support appropriate SCL transcription is unknown. Here we demonstrate
      that a 130-kilobase (kb) yeast artificial chromosome (YAC) containing the human
      SCL locus completely rescued the embryonic lethal phenotype of scl(-/-) mice.
      Rescued YAC(+) scl(-/-) mice were born in appropriate Mendelian ratios, were
      healthy and fertile, and exhibited no detectable abnormality of yolk sac, fetal
      liver, or adult hematopoiesis. The human SCL protein can therefore substitute for
      its murine homologue. In addition, our results demonstrate that the human SCL YAC
      contains the chromosomal domain necessary to direct expression to the erythroid
      lineage and to all other tissues in which SCL performs a nonredundant essential
      function.

PMID- 12010792
TI  - Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional
      hematopoietic cells in vivo.
AB  - Hematopoietic stem cells (HSCs) are unique in their capacity to maintain blood
      formation following transplantation into immunocompromised hosts. Expansion of
      HSCs in vitro is therefore important for many clinical applications but has met
      with limited success because the mechanisms regulating the self-renewal process
      are poorly defined. We have previously shown that expression of the LIM-homeobox
      gene Lhx2 in hematopoietic progenitor cells derived from embryonic stem cells
      differentiated in vitro generates immortalized multipotent hematopoietic
      progenitor cell lines. However, HSCs of early embryonic origin, including those
      derived from differentiated embryonic stem cells, are inefficient in engrafting
      adult recipients upon transplantation. To address whether Lhx2 can immortalize
      hematopoietic progenitor/stem cells that can engraft adult recipients, we
      expressed Lhx2 in hematopoietic progenitor/stem cells derived from adult bone
      marrow. This approach allowed for the generation of immortalized growth factor
      dependent hematopoietic progenitor/stem cell lines that can generate erythroid,
      myeloid, and lymphoid cells upon transplantation into lethally irradiated mice.
      When transplanted into stem cell-deficient mice, these cell lines can generate a
      significant proportion of circulating erythrocytes in primary, secondary, and
      tertiary recipients for at least 18 months. Thus, Lhx2 immortalizes multipotent
      hematopoietic progenitor/stem cells that can generate functional progeny
      following transplantation into lethally irradiated hosts and can long-term
      repopulate stem cell-deficient hosts.

PMID- 12010793
TI  - Genetically determined variation in the number of phenotypically defined
      hematopoietic progenitor and stem cells and in their response to early-acting
      cytokines.
AB  - Quantitative trait analysis may shed light on mechanisms regulating hematopoiesis
      in vivo. Strain-dependent variation existed among C57BL/6 (B6), DBA/2, and BXD
      recombinant inbred mice in the responsiveness of primitive progenitor cells to
      the early-acting cytokines kit ligand, flt3 ligand, and thrombopoietin. A
      significant quantitative trait locus was found on chromosome 2 that could not be
      confirmed in congenic mice, however, probably because of epistasis. Because it
      has been shown that alleles of unknown X-linked genes confer a selective
      advantage to hematopoietic stem cells in vivo in humans and in cats, we also
      analyzed reciprocal male D2B6F1 and B6D2F1 mice, revealing an X-linked locus
      regulating the responsiveness of progenitor and stem cells to early-acting
      factors. Among DBA/2, B6, and BXD recombinant inbred mice, correlating genetic
      variation was found in the absolute number and frequency of Lin(-)Sca1(++)kit(+)
      cells, which are highly enriched in hematopoietic progenitor and stem cells, and
      in the number of Lin(-)Sca1(++)kit(-) cells, a population whose biologic
      significance is unknown, suggesting that both populations are functionally
      related. Suggestive quantitative trait loci (QTLs) for the number of Lin(
      )Sca1(++) cells on chromosomes 2, 4, and 7 were confirmed in successive rounds of
      mapping. The locus on chromosome 2 was confirmed in congenic mice. We thus
      demonstrated genetic variation in the response to cytokines critical for
      hematopoiesis in vivo and in the pool size of cells belonging to a phenotype used
      to isolate essentially pure primitive progenitor and stem cells, and we
      identified loci that may be relevant to the regulation of hematopoiesis in steady
      state.

PMID- 12010794
TI  - CD44 variant-specific antibodies trigger hemopoiesis by selective release of
      cytokines from bone marrow macrophages.
AB  - Hemopoiesis is regulated by the complex interplay between the bone marrow
      microenvironment and hemopoietic stem cells and progenitors. The local production
      of cytokines plays a critical role in this process. Using long-term bone marrow
      cultures, we show here that monoclonal antibodies directed against the CD44 v4
      and CD44 v6 epitopes stimulate myelopoiesis (CD44 v4 and CD44 v6) and
      lymphopoiesis (CD44 v6). In the bone marrow cell population, CD44 v4 and CD44 v6
      epitopes are found virtually exclusively on double-positive bone marrow
      macrophages. The anti-CD44 v4 and v6 antibodies act on bone marrow macrophages to
      stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF) production
      (v4 and v6) and interleukin-6 (IL-6) production (v6). This profile of cytokine
      production explains the differential stimulation of hemopoiesis by the 2
      antibodies. We suggest that the antibodies mimic ligand(s) that stimulate GM-CSF
      or IL-6 production by bone marrow-derived macrophages by binding to CD44 family
      members that bear CD44 v4 and CD44 v6 epitopes on these cells.

PMID- 12010795
TI  - Interaction of endothelial microparticles with monocytic cells in vitro induces
      tissue factor-dependent procoagulant activity.
AB  - In the present study we investigated whether endothelial microparticles (EMPs)
      can bind to monocytic THP-1 cells and modulate their procoagulant properties.
      Using flow cytometry, we demonstrated that EMPs express adhesive receptors
      similar to those expressed by activated endothelial cells. Expression of
      endothelial antigens by THP-1 cells incubated with EMP was shown by
      immunoperoxidase staining and flow cytometry using antibodies directed against E
      selectin, VCAM-1, and endoglin. EMP binding to THP-1 cells was time- and
      concentration- dependent, reached a plateau at 15 minutes, and had an EMP-to
      monocyte ratio of 50:1. EMP binding was not affected by low temperature and was
      not followed by the restoration of phosphatidylserine asymmetry, suggesting that
      adhesion was not followed by fusion. A 4-hour incubation of THP-1 cells with EMP
      led to an increase in procoagulant activity as measured by clotting assay.
      Concomitantly, THP-1 exhibited increased levels of tissue factor (TF) antigen and
      TF mRNA compared to control cells. The ability of EMP to induce THP-1
      procoagulant activity was significantly reduced when THP-1 cells were incubated
      with EMP in the presence of blocking antibodies against ICAM-1 and beta2
      integrins. These results demonstrate that EMPs interact with THP-1 cells in vitro
      and stimulate TF-mediated procoagulant activity that is partially dependent on
      the interaction of ICAM-1 on EMP and its counterreceptor, beta2 integrins, on THP
      1 cells. Induction of procoagulant activity was also demonstrated using human
      monocytes, suggesting a novel mechanism by which EMP may participate in the
      dissemination and amplification of procoagulant cellular responses.

PMID- 12010796
TI  - Ultralarge multimers of von Willebrand factor form spontaneous high-strength
      bonds with the platelet glycoprotein Ib-IX complex: studies using optical
      tweezers.
AB  - Ultralarge von Willebrand factor (ULVWF) multimers have been implicated in the
      pathogenesis of the catastrophic microangiopathic disorder, thrombotic
      thrombocytopenic purpura. Spontaneous ULVWF binding to platelets has been
      ascribed to increased avidity due to the greatly increased number of binding
      sites for platelets (the A1 domain) per molecule. To address the mechanism of
      enhanced ULVWF binding to platelets, we used optical tweezers to study the
      unbinding forces from the glycoprotein Ib-IX (GP Ib-IX) complex of plasma VWF,
      ULVWF, and isolated A1 domain. The unbinding force was defined as the minimum
      force required to pull ligand-coated beads away from their attachment with GP Ib
      IX-expressing cells. Beads coated with plasma VWF did not bind to the cells
      spontaneously, requiring the modulators ristocetin or botrocetin. The force
      required to break the ristocetin- and botrocetin-induced plasma VWF-GP Ib-IX
      bonds occurred in integer multiples of 6.5 pN and 8.8 pN, respectively, depending
      on the number of bonds formed. In contrast, beads coated with either ULVWF or A1
      domain bound the cells in the absence of modulators, with bond strengths in
      integer multiples of approximately 11.4 pN for both. Thus, in the absence of
      shear stress, ULVWF multimers form spontaneous high-strength bonds with GP Ib-IX,
      while plasma VWF requires exogenous modulators. The strength of individual bonds
      formed with GP Ib-IX was similar for both ULVWF and the isolated A1 domain and
      greater than those of plasma VWF induced by either modulator. Therefore, we
      suggest that the conformational state of ULVWF multimers is more critical than
      their size for interaction with platelets.

PMID- 12010797
TI  - Platelet-erythrocyte interactions enhance alpha(IIb)beta(3) integrin receptor
      activation and P-selectin expression during platelet recruitment: down-regulation
      by aspirin ex vivo.
AB  - Activated platelets release biologically active compounds, which then recruit
      additional platelets into an evolving thrombus. We studied activation of
      alpha(IIb)beta(3) and exposure of P-selectin on platelets recruited by releasates
      obtained from collagen-treated platelets and evaluated modifications in
      prothrombotic effects of releasates induced by platelet-erythrocyte interactions
      and aspirin treatment. Releasates from collagen-stimulated platelets induced
      alpha(IIb)beta(3) activation and P-selectin exposure (monitored by flow cytometry
      using fluorescein isothiocyanate-PAC-1 and phycoerythrin-CD62 antibodies). These
      responses were markedly amplified by releasates from combined platelet
      erythrocyte suspensions. This finding demonstrates a novel mechanism(s) by which
      erythrocytes intensify platelet aggregability and mediate increased platelet
      recruitment. Because P-selectin and alpha(IIb)beta(3) are potential sites for
      platelet-leukocyte interactions, erythrocytes may also modulate leukocyte
      recruitment. Following aspirin ingestion both the recruiting capacity of platelet
      releasates and erythrocyte-induced amplification of platelet recruitment were
      down-regulated. These events represent an additional antithrombotic property of
      aspirin. We also examined the possibility that arachidonic acid, or eicosanoids
      derived therefrom, can induce a prothrombotic activity of erythrocytes. The
      TXA(2)-analog U46 619 and free arachidonate, but not PGI(2) or 12-HETE, induced
      increases in cytosolic Ca(++) and promoted phosphatidylserine (PS) exposure on a
      subpopulation of erythrocytes. PS exposure and increases in erythrocyte
      [Ca(++)](i) are associated with enhanced procoagulant activity, increased
      endothelial adhesion, and reduced erythrocyte deformability. Our findings,
      therefore, suggest that TXA(2) and arachidonic acid, derived from activated
      platelets, induce a prothrombotic phenotype on erythrocytes in proximity. We
      conclude that by these mechanisms, erythrocytes can actively contribute to
      platelet-driven thrombogenesis and microvascular occlusion.

PMID- 12010798
TI  - Isolation and characterization of an antifactor V antibody causing activated
      protein C resistance from a patient with severe thrombotic manifestations.
AB  - A 44-year-old woman with a history of severe thrombotic manifestations presented
      with a markedly reduced activated protein C-sensitivity ratio (APC-SR). DNA
      sequencing of and around the regions encoding the APC cleavage sites in the
      factor Va molecule excluded the presence of the factor VLeiden mutation and of
      other known genetic mutations. No antiphospholipid antibodies were present in the
      patient's plasma and both prothrombin time and activated partial thromboplastin
      time were normal. The total immunoglobulin fraction was isolated from the
      patient's plasma and found to induce severe APC resistance when added to normal
      plasma and to factor V-deficient plasma supplemented with increasing
      concentrations of factor V. Immunoblotting and immunoprecipitation experiments
      with the total immunoglobulin fraction purified from the patient's plasma
      demonstrated that the antibody recognizes factor V, is polyclonal, and has
      conformational epitopes on the entire factor V molecule (heavy and light chains,
      and B region). Thus, the immunoglobulin fraction interferes with the
      anticoagulant pathway involving factor V. The inhibitor was isolated by
      sequential affinity chromatography on protein G-Sepharose and factor V-Sepharose.
      The isolated immunoglobulin fraction inhibited factor Va inactivation by APC
      because of impaired cleavage at Arg306 and Arg506 of the heavy chain of the
      cofactor. The isolated immunoglobulin fraction was also found to inhibit the
      cofactor effect of factor V for the inactivation of factor VIII by the
      APC/protein S complex. Our data provide for the first time the demonstration of
      an antifactor V antibody not related to the presence of antiphospholipid
      antibodies, which is responsible for thrombotic rather than hemorrhagic symptoms.

PMID- 12010799
TI  - A novel mechanism of factor VIII protection by von Willebrand factor from
      activated protein C-catalyzed inactivation.
AB  - The protective effect of von Willebrand factor (VWF) toward activated protein C
      (APC)-catalyzed inactivation of factor VIII (FVIII) has been attributed mainly to
      inhibition of FVIII binding to phospholipid. In the present study, we
      demonstrated that VWF-mediated FVIII protection from APC also results from direct
      inhibition of FVIII binding to APC. Inhibition of FVIII binding to anhydro-APC by
      VWF would be consistent with partial or complete overlap of the FVIII binding
      sites for APC and VWF. We examined, therefore, the inhibitory effects of 6
      synthetic peptides spanning residues 1996 to 2028 around the previously localized
      APC binding region (FVIII residues 2009-2018). Peptide 2009 to 2018 inhibited
      FVIII binding to anhydro-APC by 83% (50% inhibition, 55 microM). Similarly,
      peptide 2013 to 2022 inhibited FVIII binding to VWF by 84% (50% inhibition, 25
      microM). It was also found that peptides 2009 to 2018 and 2013 to 2022 optimally
      bound to anhydro-APC and VWF, respectively. A rabbit antipeptide IgG, raised
      against peptide 2009 to 2022, blocked the binding of both anhydro-APC and VWF to
      FVIII. This immunoglobulin G inhibited proteolytic cleavage of FVIII by APC. Our
      results indicate that the essential regions for the binding of APC and VWF to
      FVIII overlap and that the protective effect of VWF on APC-catalyzed FVIII
      inactivation includes competitive inhibition of APC binding to FVIII by VWF.

PMID- 12010800
TI  - Microvascular abnormalities in sickle cell disease: a computer-assisted
      intravital microscopy study.
AB  - The conjunctival microcirculation of 18 homozygous sickle cell disease (SCD)
      patients during steady-state, painful crisis, and postcrisis conditions was
      recorded on high-resolution videotapes using intravital microscopy. Selected
      videotape sequences were subsequently coded, frame-captured, studied, and blindly
      analyzed using computer-assisted image analysis protocols. At steady-state
      (baseline), all SCD patients exhibited some of the following morphometric
      abnormalities: abnormal vessel diameter, comma signs, blood sludging, boxcar
      blood flow phenomenon, distended vessels, damaged vessels, hemosiderin deposits,
      vessel tortuosity, and microaneurysms. There was a decrease in vascularity
      (diminished presence of conjunctival vessels) in SCD patients compared with non
      SCD controls, giving the bulbar conjunctiva a "blanched" avascular appearance in
      most but not all SCD patients during steady-state. Averaged steady-state red cell
      velocity in SCD patients was slower than in non-SCD controls. During painful
      crisis, a further decrease in vascularity (caused by flow stoppage in small
      vessels) and a 36.7% +/- 5.2% decrease in large vessel (mostly venular) diameter
      resulted. In addition, the conjunctival red cell velocities either slowed
      significantly (6.6% +/- 13.1%; P <.01) or were reduced to a trickle
      (unmeasurable) during crisis. The microvascular changes observed during crisis
      were transient and reverted to steady-state baseline after resolution of crisis.
      When combined, intravital microscopy and computer-assisted image analysis
      (computer-assisted intravital microscopy) represent the availability of a
      noninvasive tool to quantify microvascular abnormalities in vascular diseases,
      including sickle cell disease. The ability to identify and relocate the same
      conjunctival vessels for longitudinal studies uniquely underscores the
      applicability of this quantitative real-time technology.

PMID- 12010801
TI  - Subcellular distribution of 3 functional platelet SNARE proteins: human
      cellubrevin, SNAP-23, and syntaxin 2.
AB  - Morphologic studies have demonstrated a process by which alpha-granule contents
      are released from platelets. Studies aimed at defining the molecular mechanisms
      of this release have demonstrated that SNARE proteins are required for alpha
      granule secretion. These observations raise the possibility that morphologic
      features of alpha-granule secretion may be influenced by the subcellular
      distribution of SNARE proteins in the platelet. To evaluate this possibility, we
      analyzed the subcellular distribution of 3 functional platelet SNARE proteins
      human cellubrevin, SNAP-23, and syntaxin 2. Exposure of streptolysin O
      permeabilized platelets to antihuman cellubrevin antibody inhibited Ca(++)
      induced alpha-granule secretion by approximately 50%. Inhibition of alpha-granule
      secretion by antihuman cellubrevin was reversed by a blocking peptide. Syntaxin 2
      and SNAP-23 have previously been demonstrated to mediate platelet granule
      secretion. The subcellular localization of the 3 SNARE proteins was determined by
      ultrastructural studies, using a pre-embedding immunonanogold method, and by
      immunoblot analysis of subcellular fractions. Immunonanogold localization
      demonstrated that approximately 80% of human cellubrevin in resting platelets was
      localized to platelet granule membranes. In contrast, SNAP-23 localized
      predominantly to plasma membrane, whereas syntaxin 2 was more evenly distributed
      among membranes of alpha-granules, the open canalicular system, and plasma
      membrane. Thus, each of these SNARE proteins has a distinct subcellular
      distribution in platelets, and each of these membrane compartments demonstrates a
      unique SNARE protein composition. This distribution provides a basis for several
      characteristics of alpha-granule secretion that include homotypic alpha-granule
      fusion and the fusion of alpha-granules with the open canalicular system and
      plasma membrane.

PMID- 12010802
TI  - Antithrombin III inhibits nuclear factor kappaB activation in human monocytes and
      vascular endothelial cells.
AB  - The serpin antithrombin III (AT III), the most important natural inhibitor of
      thrombin activity, has been shown to exert marked anti-inflammatory properties
      and proven to be efficacious in experimental models of sepsis, septic shock, and
      disseminated intravascular coagulation. Moreover, clinical observations suggest a
      possible therapeutic role for AT III in septic disorders. The molecular
      mechanism, however, by which AT III attenuates inflammatory events is not yet
      entirely understood. We show here that AT III potently blocks the activation of
      nuclear factor kappaB (NF-kappaB), a transcription factor involved in immediate
      early gene activation during inflammation. AT III inhibited agonist-induced DNA
      binding of NF-kappaB in cultured human monocytes and endothelial cells in a dose
      dependent manner, suggesting that AT III interferes with signal transduction
      leading to NF-kappaB activation. This idea was supported by demonstrating that AT
      III prevents the phosphorylation and proteolytic degradation of the inhibitor
      protein IkappaBalpha. In parallel to reducing NF-kappaB activity, AT III
      inhibited the expression of interleukin-6, tumor necrosis factor-alpha, and
      tissue factor, genes known to be under the control of NF-kappaB. The observation
      that chemically modified AT III that lacks heparin-binding capacity had no effect
      on NF-kappaB activation supports the current understanding that the inhibitory
      potency of AT III depends on the interaction of AT III with heparinlike cell
      surface glycosaminoglycans. This hypothesis was underscored by the finding that
      the AT III beta-isoform, known to have higher affinity for glycosaminoglycans, is
      more effective in preventing NF-kappaB transactivation than alpha-AT III. These
      data indicate that AT III can alter inflammatory processes via inhibition of NF
      kappaB activation.

PMID- 12010803
TI  - Host defense role of platelets: engulfment of HIV and Staphylococcus aureus
      occurs in a specific subcellular compartment and is enhanced by platelet
      activation.
AB  - Platelets can bind and phagocytose infectious microorganisms and so enable their
      transport for a prolonged time. To investigate the subcellular events of these
      interactions, platelets were incubated either with Staphylococcus aureus or with
      HIV and analyzed by electron microscopy (EM) and immuno-EM. HIV and bacteria
      internalization occurred exclusively within platelets showing morphological
      evidence of activation. Platelet activation enhanced the degree of bacterial
      internalization. Immunolabeling revealed that the engulfing vacuoles and the open
      canalicular system (OCS) were composed of distinct antigens. The engulfing
      vacuoles eventually became the site of prominent alpha-granule release. In
      platelets incubated with HIV, characteristic endocytic vacuoles were identified
      close to the plasma membrane, tightly surrounding 1 or 2 HIV particles. Virus
      particles were also located within the OCS. Immunogold labeling for the viral
      core protein p24 confirmed the presence of HIV within platelets. Finally,
      examination of platelets from a patient with acquired immunodeficiency syndrome
      and high viremia suggested that HIV endocytosis may also occur in vivo.

PMID- 12010804
TI  - Normal hemostasis but defective hematopoietic response to growth factors in mice
      deficient in phospholipid scramblase 1.
AB  - Phospholipid scramblase 1 (PLSCR1) is an endofacial plasma membrane protein
      proposed to participate in transbilayer movement of phosphatidylserine and other
      phospholipids. In addition to its putative role in the reorganization of plasma
      membrane phospholipids, PLSCR1 is a substrate of intracellular kinases that imply
      its possible participation in diverse signaling pathways underlying
      proliferation, differentiation, or apoptosis. Because PLSCR1 is prominently
      expressed in a variety of blood cells, we evaluated PLSCR activity in platelets
      and erythrocytes, and cytokine-dependent growth of hematopoietic precursor cells,
      of PLSCR1 knock-out mice. Adult PLSCR1(-/-) mice showed no obvious hematologic or
      hemostatic abnormality, and blood cells from these animals normally mobilized
      phosphatidylserine to the cell surface upon stimulation. Whereas blood cell
      counts in adult PLSCR1(-/-) mice were normal, in both fetus and newborn animals
      neutrophil counts were significantly depressed relative to age-matched wild type
      (WT). Furthermore, when compared with WT, hematopoietic precursor cells from
      PLSCR1(-/-) mice showed defective colony formation and impaired differentiation
      to mature granulocytes as stimulated by stem cell factor and granulocyte colony
      stimulating factor (G-CSF). By contrast, PLSCR1(-/-) cells showed normal colony
      formation stimulated by interleukin-3 or granulocyte-macrophage CSF, and
      expansion of megakaryocytic and erythroid progenitors by thrombopoietin or
      erythropoietin was unaffected. Stem cell factor and G-CSF were also found to
      induce marked increases in PLSCR1 levels in WT cells. Consistent with in vitro
      assays, PLSCR1(-/-) mice treated with G-CSF showed less than 50% of the
      granulocytosis observed in identically treated WT mice. These data provide direct
      evidence that PLSCR1 functionally contributes to cytokine-regulated cell
      proliferation and differentiation and suggest it is required for normal
      myelopoiesis.

PMID- 12010805
TI  - Translocation of the tetraspanin CD63 in association with human eosinophil
      mediator release.
AB  - The tetraspanin CD63 (also known as LAMP-3) has been implicated in phagocytic and
      intracellular lysosome-phagosome fusion events. It is also present in
      eosinophils, with predominant expression on crystalloid granule membrane.
      However, its role in eosinophil function is obscure. We hypothesized that CD63 is
      associated with intracellular events involved in eosinophil activation and
      mediator release. We used a combination of confocal immunofluorescence
      microscopy, flow cytometry, and secretion assays, including beta-hexosaminidase,
      eosinophil peroxidase, and RANTES, to examine CD63 expression, intracellular
      localization, and its association with cell activation and mediator release. In
      resting eosinophils, CD63 immunoreactivity was localized to plasma and
      crystalloid granule membranes. In interferon-gamma (IFN-gamma)- or C5a/CB
      stimulated cells (10 minutes), intracellular CD63 appeared to shift to the cell
      periphery and plasma membrane, while stimulation with a cocktail of interleukin-3
      (IL-3)/IL-5/granulocyte-macrophage colony-stimulating factor induced the
      appearance of discrete intracellular clusters of CD63 immunoreactivity. IFN-gamma
      induced mobilization of CD63 to the cell periphery, which coincided with
      selective mobilization of RANTES prior to its release, implying CD63 association
      with piecemeal degranulation. Agonist-induced CD63 mobilization and cell surface
      up-regulation was associated with beta-hexosaminidase, eosinophil peroxidase, and
      RANTES release. Dexamethasone as well as genistein (a broad-spectrum inhibitor of
      tyrosine kinases) inhibited agonist-induced intracellular mobilization of CD63
      and RANTES together with cell surface up-regulation of CD63 and mediator release.
      This is the first report of an association between CD63 mobilization and agonist
      induced selective mediator release, which may imply the involvement of CD63 in
      eosinophil activation and piecemeal degranulation.

PMID- 12010806
TI  - Extracellular signal-regulated kinase mediates granulocyte-macrophage colony
      stimulating factor messenger RNA stabilization in tumor necrosis factor-alpha
      plus fibronectin-activated peripheral blood eosinophils.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is critical for
      promoting the long-term survival of lung- or airway-based eosinophils.
      Previously, we have shown that fibronectin and tumor necrosis factor alpha
      induced autocrine production of GM-CSF that markedly enhanced eosinophil
      survival. Cytokine release was preceded by and dependent on messenger RNA (mRNA)
      stabilization. Here, we show that mitogen-activated protein kinase (MAPK)
      activation is responsible for GM-CSF mRNA stabilization in peripheral blood
      eosinophils (pbeos). Activation of extracellular signal-regulated kinase (ERK)
      but not p38 correlated with GM-CSF mRNA stability. Although ERK inhibition
      completely prevented GM-CSF mRNA stabilization, p38 inhibition had a partial
      effect. To establish which MAPK was crucial, we transduced pbeos with dominant
      active TatMEK1(E) or TatMKK3b(E) proteins that selectively phosphorylate ERK or
      p38, respectively. These studies showed that ERK but not p38 was sufficient for
      GM-CSF mRNA stabilization. These data are in contradistinction to the c-Jun NH(2)
      terminal kinase-mediated regulation of interleukin 2 and 3 mRNAs and suggest
      unique regulatory features for GM-CSF mRNA in eosinophils.

PMID- 12010807
TI  - Defective T-helper cell function after T-cell-depleting therapy affecting naive
      and memory populations.
AB  - Impaired T-cell function after T-cell- depleting (TCD) therapy has been
      hypothesized to be related to a transient predominance of extrathymically
      expanding memory T cells. To test whether after TCD therapy the naive T-helper
      cell population is functionally intact, the in vitro immune response of
      CD4(+)CD45RA(+) (naive) and of CD4(+)CD45RA(-) (memory) cells to polyclonal
      mitogens (immobilized anti-CD3, phytohemagglutinin) was analyzed by flow
      cytometry in 22 pediatric patients after high-dose chemotherapy (including 5
      after autologous and 5 after allogeneic stem cell support). At 1 to 3 months
      after TCD therapy, patient samples showing decreased lymphoproliferative
      responses also showed a reduced induction of the early activation marker CD69 by
      CD4(+) T cells from 4 to 72 hours after stimulation even when supplemented with
      exogenous interleukin-2. This defect affected CD4(+)CD45RA(-) cells, but,
      strikingly, also CD4(+)CD45RA(+) cells, including samples in which
      CD4(+)CD45RA(+) cells were more than 90/microL, thus indicating ongoing
      thymopoiesis. Histogram analyses showed the median peak channel of CD69 in
      control CD4(+)CD45RA(+) cells rising 98-fold (median) but only 28-fold in patient
      cells (P <.0001). Apoptosis as detected by annexin V staining was increased in
      resting patient CD4(+) T cells (25% versus 6%) and also affected CD4(+)CD45RA(+)
      cells (12% versus 5%, P <.01). When peripheral blood mononuclear cells (PBMCs)
      were enriched for T cells, stimulatory responses of CD4(+) cells and of
      CD4(+)CD45RA(+) cells markedly improved. Thus, after TCD therapy suppressor
      factors contained in the non-T-cell fraction of PBMCs may affect T-helper cells
      irrespective of their naive or memory phenotype thus extending T-cell dysfunction
      to the presumably thymus-dependently regenerated T cells.

PMID- 12010808
TI  - The monoclonal antibody CHO-131 binds to a core 2 O-glycan terminated with sialyl
      Lewis x, which is a functional glycan ligand for P-selectin.
AB  - Core 2 O-glycans terminated with sialyl-Lewis x (sLe(X)) are functionally
      important oligosaccharides that endow particular macromolecules with high
      affinity glycan ligands for the selectin family. To date, antibodies that
      recognize these structures on leukocytes have not been described. We characterize
      such a monoclonal antibody (mAb) here (CHO-131). The binding specificity of CHO
      131 was directly examined by means of synthetic glycopeptides containing precise
      O-glycan structures. CHO-131 bound to sLe(X) extended from a core 2 branch (C2-O
      sLe(X)), but CHO-131 demonstrated no reactivity if this oligosaccharide lacked
      fucose or if sLe(X) was extended from a core 1 branch. Using transfected cell
      lines, we found that CHO-131 binding required the functional activity of the
      glycosyltransferases alpha2,3-sialyltransferase, alpha1,3-fucosyltransferase-VII,
      and core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT). The C2-O-sLe(X) motif
      occurs primarily on sialomucins and has been directly shown to contribute to high
      affinity P-selectin glycoprotein ligand-1 binding by P-selectin. Indeed, CHO-131
      staining of neutrophils was diminished following sialomucin removal by O
      glycoprotease, and its reactivity with transfected hematopoietic cell lines
      correlated with the expression of P-selectin ligands. CHO-131 also stained a
      small population of lymphocytes that were primarily CD3(+), CD4(+), and CD45RO(+)
      and represented a subset (37.8% +/- 18.3%) of cutaneous lymphocyte-associated
      antigen (CLA) T cells, distinguished by the mAb HECA-452, which detects sLe(X)
      related glycans. Unlike anti-sLe(X) mAbs, CHO-131 binding also indicates C2GnT
      activity and demonstrates that CLA T cells are heterogeneous based on the glycan
      structures they synthesize. These findings support evidence that differential
      C2GnT activity results in T-cell subsets that express ligands for E-selectin, P
      selectin, or both.

PMID- 12010809
TI  - Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an
      inhibitor of the caspase cascade.
AB  - Caspase-8 (Fas-associating protein with death domain-like interleukin-1beta-
      converting enzyme [FLICE]/MACH/Mch5) belongs to a family of cysteine proteases
      presumed to be the apex of the apoptotic signaling pathways. We recently reported
      the presence of a novel isoform of caspase-8, named caspase-8L, generated by the
      alternative splicing of human caspase-8 gene, from human peripheral blood
      lymphocytes by reverse transcriptase-polymerase chain reaction. We herein report
      a functional analysis of caspase-8L in the Fas-mediated apoptotic pathway.
      Caspase-8L is missing the catalytic site of caspase-8 but retains 2 N-terminal
      repeats of the death-effector domain. The caspase-8L messenger RNA was detected
      in various tissues but not in any cell lines examined. In human peripheral blood
      lymphocytes, caspase-8L was strongly suggested to be expressed at the protein
      level. In MCF-7 cells, caspase-8L transfection itself did not affect cell
      viability but instead inhibited the apoptosis induced by the cotransfection of
      caspase-8 in a dominant negative manner. Moreover, Fas-mediated apoptosis was
      inhibited in caspase-8L-transfected Jurkat cells, which were associated with a
      reduction in the caspase-8 catalytic activity. In vitro binding assays
      demonstrated that caspase-8L bound to FADD (Fas-associating protein with death
      domain) and caspase-8a and blocked the binding of caspase-8 to FADD. In in vivo
      binding assays, transfected caspase-8L bound to endogenous FADD. Thus, caspase-8L
      acts as an inhibitor of caspase-8 by interfering with the binding of caspase-8 to
      FADD and is involved in the regulation of Fas-mediated apoptosis.

PMID- 12010810
TI  - Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma:
      therapeutic applications.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) confers significant
      survival potential in a variety of tumors. Several established or novel anti
      multiple myeloma (anti-MM) agents, such as dexamethasone, thalidomide, and
      proteasome inhibitors (PS-341), inhibit NF-kappaB activity as part of their
      diverse actions. However, studies to date have not delineated the effects of
      specific inhibition of NF-kappaB activity in MM. We therefore investigated the
      effect of SN50, a cell-permeable specific inhibitor of NF-kappaB nuclear
      translocation and activity, on MM cells. SN50 induced apoptosis in MM cell lines
      and patient cells; down-regulated expression of Bcl-2, A1, X-chromosome-linked
      inhibitor-of-apoptosis protein (XIAP), cellular inhibitor-of-apoptosis protein 1
      (cIAP-1), cIAP-2, and survivin; up-regulated Bax; increased mitochondrial
      cytochrome c release into the cytoplasm; and activated caspase-9 and caspase-3,
      but not caspase-8. We have previously demonstrated that tumor necrosis factor
      alpha (TNF-alpha) is present locally in the bone marrow microenvironment and
      induces NF-kappaB-dependent up-regulation of adhesion molecules on both MM cells
      and bone marrow stromal cells, with resultant increased adhesion. In this study,
      TNF-alpha alone induced NF-kappaB nuclear translocation, cIAP-1 and cIAP-2 up
      regulation, and MM cell proliferation; in contrast, SN50 pretreatment sensitized
      MM cells to TNF-alpha-induced apoptosis and cleavage of caspase-8 and caspase-3,
      similar to our previous finding of SN50-induced sensitization to apoptosis
      induced by the TNF-alpha family member TNF-related apoptosis-inducing ligand
      (TRAIL)/Apo2L. Moreover, SN50 inhibited TNF-alpha-induced expression of another
      NF-kappaB target gene, intercellular adhesion molecule-1. Although the p38
      inhibitor PD169316 did not directly kill MM cells, it potentiated the apoptotic
      effect of SN50, suggesting an interaction between the p38 and NF-kappaB pathways.
      Our results therefore demonstrate that NF-kappaB activity in MM cells promotes
      tumor-cell survival and protects against apoptotic stimuli. These studies provide
      the framework for targeting NF-kappaB activity in novel biologically based
      therapies for MM.

PMID- 12010811
TI  - B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of
      activated, antigen-experienced B lymphocytes.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is considered an accumulative disease
      of antigen-naive CD5(+) B lymphocytes that circulate in the resting state.
      However, to evaluate the possibility that B-CLL cells resemble antigen
      experienced and activated B cells, we analyzed the expression of markers of
      cellular activation and differentiation on CD5(+)CD19(+) cells from B-CLL
      patients and from age-matched healthy donors. The leukemic cells from all B-CLL
      patients, including those that lack significant numbers of V gene mutations, bear
      the phenotype of activated B cells based on the overexpression of the activation
      markers CD23, CD25, CD69, and CD71 and the underexpression of CD22, Fcgamma
      receptor IIb, CD79b, and immunoglobulin D that are down-regulated by cell
      triggering and activation. Furthermore, these leukemic cells resemble antigen
      experienced lymphocytes in the underexpression of molecules that are down
      regulated by cell triggering and in the uniform expression of CD27, an identifier
      of memory B cells. A comparison of the phenotypes of B-CLL patients with and
      without immunoglobulin V gene mutations suggests that the 2 subgroups differ both
      in specific marker expression (CD69, CD71, CD62 L, CD40, CD39, and HLA-DR) and in
      the time since antigenic stimulation, based on the reciprocal relationship of
      CD69 and CD71 expression. These findings imply that the leukemic cells from all B
      CLL cases (irrespective of V gene mutations) exhibit features of activated and of
      antigen-experienced B lymphocytes and that the B-CLL cells that differ in
      immunoglobulin V genotype may have different antigen-encounter histories.

PMID- 12010812
TI  - Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas.
AB  - Caspase 10 (Mch4/FLICE2) is a caspase homologous to caspase 8. A recent report
      described that inherited CASP10 gene mutations underlie defective lymphocyte and
      dendritic cell apoptosis in autoimmune lymphoproliferative syndrome (ALPS). In
      this study, to explore the possibility that mutation of this gene might be
      involved in the development of non-Hodgkin lymphoma (NHL), we have analyzed the
      entire coding region and all splice sites of the CASP10 gene for the detection of
      somatic mutations in 117 human NHLs. Overall, 17 NHLs (14.5%) were found to have
      CASP10 mutations, which were identified in the coding regions of the prodomain (n
      = 3), the p17 large protease subunit (n = 11), and the p12 small protease subunit
      (n = 3). We expressed the tumor-derived caspase 10 mutants in 293 cells and found
      that apoptosis was suppressed. These data suggest that the inactivating mutations
      of the CASP10 gene might lead to the loss of its apoptotic function and
      contribute to the pathogenesis of some human NHLs.

PMID- 12010813
TI  - The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of
      childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic
      characteristics at diagnosis and relapse.
AB  - Acute lymphoblastic leukemia cells from 19 children, including 7 who remain in
      first complete remission (CR1), were engrafted into nonobese diabetic/severe
      combined immunodeficient (NOD/SCID) mice. High-level infiltration of bone marrow,
      spleen, and liver was observed, with variable infiltration of other organs. The
      immunophenotypes of xenografts were essentially unaltered compared with the
      original patient sample. In addition, sequencing of the entire p53 coding region
      revealed no mutations in 14 of 14 xenografts (10 from patients at diagnosis and 4
      at relapse). Cells harvested from the spleens of engrafted mice readily
      transferred the leukemia to secondary and tertiary recipients. To correlate
      biologic characteristics of xenografts with clinical and prognostic features of
      the patients, the rates at which individual leukemia samples engrafted in
      NOD/SCID mice were analyzed. Differences in biologic correlates were encountered
      depending on stage of disease: a direct correlation was observed between the rate
      of engraftment and length of CR1 for samples harvested at relapse (r = 0.96; P
      =.002), but not diagnosis (r = 0.38; P =.40). In contrast, the in vivo responses
      of 6 xenografts to vincristine showed a direct correlation (r = 0.96; P =.002)
      between the length of CR1 and the rate at which the leukemia cell population
      recovered following vincristine treatment, regardless of whether the xenografts
      were derived from patients at diagnosis or relapse. This study supports previous
      findings that the NOD/SCID model of childhood ALL provides an accurate
      representation of the human disease and indicates that it may be of value to
      predict relapse and design alternative treatment strategies in a patient-specific
      manner.

PMID- 12010814
TI  - In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell
      death in context of maturation stage, responsiveness to interleukin 7, and early
      cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia.
AB  - Within childhood T-cell acute lymphoblastic leukemia (T-ALL), patients with a
      cortical (CD1a(+)) immunophenotype have been identified as a subgroup with
      favorable outcome in the acute lymphoblastic leukemia-Berlin-Frankfurt-Munster
      (ALL-BFM), Cooperative study group for childhood acute lymphoblastic leukemia
      (COALL) and Pediatric Oncology Group studies. We investigated in leukemic samples
      of children with T-ALL (n = 81) whether the different in vivo therapy response
      could be linked to differential in vitro susceptibility to apoptotic cell death.
      The extent of dexamethasone- as well as doxorubicin-induced apoptosis, detected
      by annexin V staining, positively correlated with the expression levels of CD1a
      (Spearman correlation coefficient, r(s) = 0.3 and 0.4, respectively; P <.01).
      When compared to cortical T-ALL, mature (CD1a(-), surface CD3(+)) T-ALL were
      significantly more resistant to doxorubicin, and immature, pro-/pre-T-ALL were
      more resistant to both drugs (P <.05). Apoptosis-related parameters (Bax, Bcl-2,
      CD95, and CD95-induced apoptosis) did not account for differential susceptibility
      to drug-induced apoptosis. By contrast, an interleukin 7-induced rescue of
      leukemic cells from spontaneous apoptosis, recently proposed to reflect distinct
      developmental stages and apoptotic programs in T-ALL, was highly associated with
      susceptibility to dexamethasone- but not doxorubicin-induced apoptosis (P <.001
      versus P =.08). Analysis of clinical data showed that in vitro susceptibility to
      dexamethasone (but not to doxorubicin) closely correlated with early in vivo
      therapy response characterized by percentages of blast cells in bone marrow on
      day 15 (r(s) = -0.46, P =.001). Taken together, the in vitro assessment of drug
      induced apoptosis revealed maturation-dependent differences within childhood T
      ALL. The enhanced sensitivity to both drugs in cortical T-ALL might account for
      the better in vivo treatment response of this prognostically favorable T-ALL
      subgroup.

PMID- 12010815
TI  - Down-regulation of candidate tumor suppressor genes within chromosome band
      13q14.3 is independent of the DNA methylation pattern in B-cell chronic
      lymphocytic leukemia.
AB  - Loss of genomic material from chromosomal band 13q14.3 is the most common genetic
      imbalance in B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell
      lymphoma, pointing to the involvement of this region in a tumor suppressor
      mechanism. From the minimally deleted region, 3 candidate genes have been
      isolated, RFP2, BCMS, and BCMSUN. DNA sequence analyses have failed to detect
      small mutations in any of these genes, suggesting a different pathomechanism,
      most likely haploinsufficiency. We, therefore, tested B-CLL patients for
      epigenetic aberrations by measuring expression of genes from 13q14.3 and
      methylation of their promotor region. RB1, CLLD7, KPNA3, CLLD6, and RFP2 were
      down-regulated in B-CLL patients as compared with B cells of healthy donors, with
      RFP2 showing the most pronounced loss of expression. To test whether this loss of
      gene expression is associated with methylation of CpG islands in the respective
      promotor regions, we performed methylation-sensitive quantitative polymerase
      chain reaction analyses and bisulfite sequencing on DNA from B-CLL patients. No
      difference in the methylation patterns could be detected in any CpG island of the
      minimally deleted region. Down-regulation of genes within chromosomal band
      13q14.3 in B-CLL is in line with the concept of haploinsufficiency, but this
      tumor-specific phenomenon is not associated with DNA methylation.

PMID- 12010816
TI  - BCR-ABL-induced adhesion defects are tyrosine kinase-independent.
AB  - The t(9;22) chromosomal translocation results in expression of P210(BCR-ABL), a
      fusion protein necessary for the development of chronic myelogenous leukemia
      (CML). The constitutive activation of the P210(BCR-ABL) tyrosine kinase results
      in phosphorylation of multiple signaling pathways leading to the transformed
      phenotype. Additionally, extracellular interactions between P210(BCR-ABL)
      expressing progenitor cells and bone marrow stroma may provide external signals
      that facilitate CML development. In contrast to the intracellular signaling
      pathways involved in CML, little is known about how P210(BCR-ABL) expression
      modifies cell-cell and cell-substratum interactions. To investigate the role of
      P210(BCR-ABL) in modulating cellular adhesion, we used a highly sensitive and
      quantitative cell detachment apparatus that measures the strength of association
      between a population of cells and an adhesive matrix. Our findings show that
      P210(BCR-ABL) expression increased adhesion nearly 2-fold between the
      myeloblastic cell line, 32D, and fibronectin compared to a control vector. We
      then investigated whether abnormal adhesion due to P210(BCR-ABL) expression was
      caused by its tyrosine kinase activity. A quantitative analysis of cell
      fibronectin adhesion found that neither expression of a kinase-inactive P210(BCR
      ABL) mutant in 32D cells or attenuation of kinase activity by STI571 (imatinib
      mesylate) in 32D cells transduced with wild-type P210(BCR-ABL) could correct the
      nearly 2-fold increase in cell-fibronectin adhesion. Similarly, STI571 treatment
      of Meg-01 cells, a P210(BCR-ABL)-expressing cell line derived from a patient in
      blast crisis, failed to inhibit adhesion to fibronectin. Together, our results
      indicate that changes in adhesion induced by P210(BCR-ABL) are independent of its
      tyrosine kinase activity.

PMID- 12010817
TI  - Diagnostic and prognostic value of bone marrow angiogenesis and megakaryocyte c
      Mpl expression in essential thrombocythemia.
AB  - The lack of diagnostic certainty in some patients makes it difficult to
      distinguish between primary and secondary forms of thrombocytosis. To augment
      current diagnostic studies for thrombocytosis, we retrospectively evaluated
      clinical records and bone marrow trephine specimens of 183 patients with
      thrombocytosis-164 with essential thrombocythemia (ET), 19 with reactive
      thrombocytosis (RT)-for bone marrow angiogenesis, bone marrow megakaryocyte c-Mpl
      staining, and morphologic evidence of megakaryocyte proliferation. Angiogenesis
      was increased in patients with ET compared with healthy controls (P <.0001) and
      patients with RT (P =.006). In addition, an increase in angiogenesis was
      associated with certain disease features such as splenomegaly (P =.004) and
      reticulin fibrosis (P =.005). Decreased megakaryocyte c-Mpl staining was observed
      in a heterogeneous pattern in ET compared with healthy controls (P <.0001) and RT
      (P <.0001). Histologic stratifying criteria incorporating increased angiogenesis,
      decreased megakaryocyte c-Mpl expression, and marked megakaryocyte proliferation
      in the bone marrow was highly sensitive (97%) and specific (95%) for
      distinguishing ET from RT (P <.0001). However, with the current duration of
      follow-up available on the patients, none of the histologic features evaluated
      have yet demonstrated prognostic value for subsequent clinical course, vascular
      events, or survival.

PMID- 12010818
TI  - Insulinlike growth factor-I signaling in multiple myeloma: downstream elements,
      functional correlates, and pathway cross-talk.
AB  - In multiple myeloma cells, insulinlike growth factor-I (IGF-I) activates 2
      distinct signaling pathways, mitogen-activated protein kinase (MAPK) and
      phosphoinositol 3-kinase (PI-3K), leading to both proliferative and antiapoptotic
      effects. However, it is unclear through which of these cascades IGF-I regulates
      these different responses. The present studies identify a series of downstream
      targets in the PI-3K pathway, including glycogen synthase kinase-3beta, p70S6
      kinase, and the 3 members of the Forkhead family of transcription factors. The
      contribution of the MAPK and PI-3K pathways and, where possible, individual
      elements to proliferation and apoptosis was evaluated by means of a series of
      specific kinase inhibitors. Both processes were regulated almost exclusively by
      the PI-3K pathway, with only minor contributions associated with the MAPK
      cascade. Within the PI-3K cascade, inhibition of p70S6 kinase led to significant
      decreases in proliferation and protection from apoptosis. Activation of p70S6
      kinase could also be prevented by MAPK inhibitors, indicating regulation by both
      pathways. The Forkhead transcription factor FKHRL1 was observed to provide a dual
      effect in that phosphorylation upon IGF-I treatment resulted in a loss of ability
      to inhibit proliferation and induce apoptosis. The PI-3K pathway was additionally
      shown to exhibit cross-talk and to regulate the MAPK cascade, as inhibition of PI
      3K prevented activation of Mek1/2 and other downstream MAPK elements. These
      results define important elements in IGF-I regulation of myeloma cell growth and
      provide biological correlates critical to an understanding of growth-factor
      modulation of proliferation and apoptosis.

PMID- 12010819
TI  - Targeting Raf-1 gene expression by a DNA enzyme inhibits juvenile myelomonocytic
      leukemia cell growth.
AB  - Juvenile myelomonocytic leukemia (JMML) is an aggressive childhood disorder with
      few therapeutic options. Granulocyte-macrophage colony-stimulating factor (GM
      CSF) and tumor necrosis factor-alpha (TNF-alpha) promote JMML cell growth. A
      hyperactive function of the ras oncogene is a hallmark of JMML. We therefore
      targeted the protein kinase Raf-1 downstream of Ras using a DNA enzyme that
      degrades mRNA-Raf-1. Western blots of JMML cell lysates revealed phosphorylated
      Raf-1 protein, indicating constitutive activation. Addition of GM-CSF, but not
      TNF-alpha, increased phosphorylation of both Raf-1 and the mitogen-activated
      protein kinases (MAPKs) JNK-1 and ERK-1. Depletion of Raf-1 protein markedly
      impaired activation of MAPKs, induced substantial inhibition of JMML cell colony
      formation, and virtually abolished GM-CSF hypersensitivity in JMML cells.
      Exogenous TNF-alpha, but not GM-CSF, restored colony formation of JMML cells
      pretreated with the enzyme. We could not detect any effect of the enzyme on the
      proliferation of normal bone marrow cells, indicating its specificity and
      potential safety. When immunodeficient mice engrafted with JMML cells were
      treated continuously with the enzyme via a peritoneal osmotic mini-pump for 4
      weeks, a profound reduction in the JMML cell numbers in the recipient murine bone
      marrows was found. We conclude that GM-CSF is a chief regulator of JMML growth
      and exerts its proleukemic effects primarily via the Ras/Raf-1 signaling cascade.
      TNF-alpha plays a permissive role, being dependent upon GM-CSF to induce JMML
      cell proliferation. The DNA enzyme efficiently catabolized mRNA-Raf-1 with
      subsequent inhibition of JMML cell growth, suggesting its potential as a
      mechanism-based therapy in this fatal leukemia.

PMID- 12010820
TI  - CD4(+), CD56(+) DC2 acute leukemia is characterized by recurrent clonal
      chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe
      Francais de Cytogenetique Hematologique.
AB  - CD4(+), CD56(+) DC2 malignancies constitute a novel disease entity, which has
      recently been shown to arise from a transformed lymphoid-related plasmacytoid
      dendritic cell (DC2). Diagnosis is primarily based on a particular
      immunophenotype with tumor cells expressing CD4 and CD56 antigens in the absence
      of common lymphoid or myeloid lineage markers. Little is currently known about
      the cytogenetic features of this disease entity. In this setting, the Groupe
      Francais de Cytogenetique Hematologique (GFCH) initiated a cytogenetic study of
      18 adults and 3 children with CD4(+), CD56(+) DC2 acute leukemia using
      conventional and fluorescence in situ hybridization/24-color karyotyping. Clonal,
      mostly complex chromosome aberrations were found in 14 patients (66%). Six major
      recurrent chromosomal targets were defined. These were 5q, 12p, 13q, 6q, 15q, and
      9, which were involved in 72% (5q), 64% (12p and 13q), 50% (6q), 43% (15q), and
      28% (monosomy 9) of cases, respectively. Cytogenetic features can be summarized
      as follows: (1) gross genomic imbalances (mostly losses) predominate, (2) no
      single anomaly can be considered as specific, whereas their
      combination/accumulation is, and (3) both lymphoid and myeloid lineage-associated
      rearrangements are observed in unusual combinations in the same cell. This is
      suggestive of complex multistep tumorigenic mechanisms and is supportive of the
      hypothesis that CD4(+), CD56(+) DC2 acute leukemia may arise from an
      undifferentiated nonmyeloid nonlymphoid progenitor cell. In conclusion, the
      present study documents for the first time the existence of a characteristic
      cytogenetic profile for this novel disease entity.

PMID- 12010821
TI  - Neutrophil activation by heme: implications for inflammatory processes.
AB  - Heme, a ubiquitous iron-containing compound, is present in large amounts in many
      cells and is inherently dangerous, particularly when it escapes from
      intracellular sites. The release of heme from damaged cells and tissues is
      supposed to be higher in diseases such as malaria and hemolytic anemia or in
      trauma and hemorrhage. We investigated here the role of free ferriprotoporphyrin
      IX (hemin) as a proinflammatory molecule, with particular attention to its
      ability to activate neutrophil responses. Injecting hemin into the rat pleural
      cavity resulted in a dose-dependent migration of neutrophils, indicating that
      hemin is able to promote the recruitment of these cells in vivo. In vitro, hemin
      induced human neutrophil chemotaxis and cytoskeleton reorganization, as revealed
      by the increase of neutrophil actin polymerization. Exposure of human neutrophils
      to 3 microM hemin activated the expression of the chemokine interleukin-8, as
      demonstrated by quantitative reverse-transcription polymerase chain reaction,
      indicating a putative molecular mechanism by which hemin induces chemotaxis in
      vivo. Brief incubation of human neutrophils with micromolar concentrations of
      hemin (1-20 microM) triggered the oxidative burst, and the production of reactive
      oxygen species was directly proportional to the concentration of hemin added to
      the cells. Finally, we observed that human neutrophil protein kinase C was
      activated by hemin in vitro, with a K(1/2) of 5 microM. Taken together, these
      results suggest a role for hemin as a proinflammatory agent able to induce
      polymorphonuclear neutrophil activation in situations of clinical relevance, such
      as hemolysis or hemoglobinemia.

PMID- 12010822
TI  - Antidisialoganglioside/granulocyte macrophage-colony-stimulating factor fusion
      protein facilitates neutrophil antibody-dependent cellular cytotoxicity and
      depends on FcgammaRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell
      adhesion and azurophil granule exocytosis.
AB  - Polymorphonuclear leukocytes (PMNs) mediate antibody-dependent cellular
      cytotoxicity (ADCC), which is increased by the addition of granulocyte-macrophage
      colony-stimulating factor (GM-CSF). We sought to determine whether PMN ADCC also
      would be increased by the addition of an antibody/GM-CSF fusion protein and
      whether this would be associated with the up-regulation and activation of Mac-1
      (CD11b/CD18) and with azurophil granule exocytosis. ADCC against LA-N-1 human
      neuroblastoma cells was evaluated with 4-hour calcein acetoxymethyl ester
      (calcein-AM) microcytotoxicity assay, electron microscopy, and multi-parameter
      flow cytometry. With the calcein-AM assay, LA-N-1 cell survival was 10%, 55%, and
      75% when PMN ADCC was mediated by the antidisialoganglioside (anti-GD2)
      immunocytokine hu14.18/GM-CSF, by monoclonal antibody (mAb) hu14.18 mixed with GM
      CSF, and by hu14.18 alone. Function-blocking mAbs demonstrated that FcgammaRII
      and FcgammaRIII were required for ADCC with hu14.18 alone or mixed with GM-CSF,
      but that only FcgammaRII was required for ADCC with hu14.18/GM-CSF. ADCC mediated
      by hu14.18 and hu14.18/GM-CSF was Mac-1 dependent. Electron microscopy
      demonstrated the greatest PMN adhesion, spreading, and lysis of targets with
      hu14.18/GM-CSF. Monoclonal antibodies blocking Mac-1 function allowed the
      tethering of PMN to targets with hu14.18/GM-CSF but prevented adhesion,
      spreading, and cytolysis. Flow cytometry showed that hu14.18 with or without GM
      CSF and hu14.18/GM-CSF all mediated Mac-1-dependent PMN-target cell conjugate
      formation but that GM-CSF was required for the highest expression and activation
      of Mac-1, as evidenced by the mAb24-defined beta(2)-integrin activation epitope.
      Hu14.18/GM-CSF induced the highest sustained azurophil granule exocytosis, almost
      exclusively in PMNs with activated Mac-1. Thus, hu14.18/GM-CSF facilitates PMN
      ADCC against neuroblastoma cells associated with FcgammaRII and Mac-1-dependent
      enhanced adhesion and degranulation.

PMID- 12010823
TI  - Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto
      cells by short-term culture of purified human CD34(+) cells.
AB  - Stem cell-dose escalation is one way to overcome immune rejection of incompatible
      stem cells. However, the number of hematopoietic precursors required for
      overcoming the immune barrier in recipients pretreated with sublethal regimens
      cannot be attained with the state-of-the-art technology for stem cell
      mobilization. This issue was addressed by the observation that cells within the
      human CD34(+) population are endowed with veto activity. In the current study, we
      demonstrated that it is possible to harvest about 28- to 80-fold more veto cells
      on culturing of purified CD34(+) cells for 7 to 12 days with an early-acting
      cytokine mixture including Flt3-ligand, stem cell factor, and thrombopoietin.
      Analysis of the expanded cells with fluorescence-activated cell-sorter scanning
      revealed that the predominant phenotype of CD34(+)CD33(-) cells used at the
      initiation of the culture was replaced at the end of the culture by cells
      expressing early myeloid phenotypes such as CD34(+)CD33(+) and CD34(-)CD33(+).
      These maturation events were associated with a significant gain in veto activity
      as exemplified by the minimal ratio of veto to effector cells at which
      significant veto activity was detected. Thus, whereas purified unexpanded CD34(+)
      cells exhibited veto activity at a veto-to-effector cell ratio of 0.5, the
      expanded cells attained an equivalent activity at a ratio of 0.125. The
      availability of novel sources of veto cells such as those in this study might
      contribute to the realization of immunologic tolerance in "minitransplants,"
      without any risk of graft-versus-host disease.

PMID- 12010824
TI  - Total body irradiation causes profound changes in endothelial traffic molecules
      for hematopoietic progenitor cell recruitment to bone marrow.
AB  - Nonirradiated bone marrow (BM) venules and sinusoids in murine skull support
      hematopoietic progenitor cell (HPC) rolling through constitutively expressed
      endothelial (P- and E-) selectins and VCAM-1. Using intravital microscopy, we
      tested whether host conditioning with total body irradiation (TBI) changes the
      molecular mechanisms by which murine HPCs from fetal livers (FL) interact with BM
      endothelial cells. Although a high dose of TBI did not affect the overall
      frequency of HPC rolling in BM microvessels, the underlying molecular mechanisms
      differed from those in nonirradiated BM. TBI induced VCAM-1 up-regulation in BM
      microvessels, whereas P-selectin expression was reduced and the low baseline
      level of E-selectin remained unchanged. Only the administration of anti-VCAM-1,
      but not anti-P- or -E-selectin monoclonal antibodies, decreased FL HPC rolling.
      Rolling was frequently followed by firm arrest (sticking), even in nonirradiated
      BM microvessels in which sticking was entirely pertussis toxin-insensitive-that
      is, Galpha(i)-coupled signaling events (eg, through chemokines) were apparently
      not required. TBI increased the frequency of sticking FL HPC. This irradiation
      induced additional sticking was reversed when FL HPCs were pretreated with
      pertussis toxin, suggesting that TBI induced elevated expression of a Galpha(i)
      protein-coupled chemotactic signal in the BM. This chemoattractant was probably
      distinct from SDF-1alpha because, unlike adult HPCs, FL HPCs (day 11 of
      gestation) responded poorly to SDF-1alpha in vitro. These results demonstrate
      that TBI induces profound changes in the expression of endothelial traffic
      molecules in the BM, and they indicate that FL HPCs can home to the BM in the
      absence of SDF-1alpha and other Galpha(i)-protein-coupled signals.

PMID- 12010825
TI  - Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but
      spares the graft-versus-leukemia function of the bone marrow allografts in a
      murine bone marrow transplantation model.
AB  - The purpose of the present study was to evaluate the effects of graft-versus-host
      disease (GVHD) prophylaxis with the Janus kinase 3 (JAK3) inhibitor WHI
      P131/JANEX-1 on the graft-versus-leukemic (GVL) function of marrow allografts in
      mice undergoing bone marrow transplantation (BMT) after being challenged with an
      otherwise invariably fatal dose of BCL-1 leukemia cells. GVHD prophylaxis using
      WHI-P131 markedly improved the survival outcome after BMT. The probability of
      survival at 30 days after BMT was 11% +/- 6% for vehicle-treated recipients
      (median survival time, 25 days) versus 63% +/- 12% for recipients treated with
      WHI-P131 (median survival time, 36 days; P <.0001). Because WHI-P131 is devoid of
      antileukemic activity against BCL-1 leukemia cells, this marked improvement in
      survival outcome was due to reduced incidence of GVHD-associated fatalities
      combined with sustained GVL function of the allografts in the WHI-P131 group.
      Notably, adoptive transfer experiments demonstrated that the spleens of WHI-P131
      treated allograft recipients contained less than 0.001% BCL-1 cells. Notably,
      GVHD prophylaxis with WHI-P131 plus methotrexate resulted in 100% survival of
      mice receiving allotransplants challenged with an otherwise invariably fatal dose
      of BCL-1 leukemia. Taken together, our results provide strong experimental
      evidence that GVHD prophylaxis using WHI-P131 does not impair the GVL function of
      the allografts and consequently contributes to an improved post-BMT survival
      outcome of the recipient mice.

PMID- 12010826
TI  - The clinical significance of human leukocyte antigen (HLA) allele compatibility
      in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and
      HLA-DR matched unrelated donors.
AB  - To improve the clinical outcome of allogeneic hematopoietic stem cell
      transplantation from an unrelated donor, the identification of human leukocyte
      antigen (HLA) alleles responsible for immunologic events such as graft-versus
      host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is
      essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively
      performed in 1298 donor-patient pairs in cases where marrow was donated from
      serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA
      A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the
      synergistic effect of the HLA-C allele mismatch with other HLA allele mismatches
      on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be
      a significant factor for the occurrence of chronic GVHD. HLA class I (A, B,
      and/or C) allele mismatch caused a significantly higher incidence of engraftment
      failure than HLA match. Significant association of HLA-C allele mismatch with
      leukemia relapse was not observed. As the result of these events, HLA-A and/or
      HLA-B allele mismatch reduced overall survival remarkably in both standard-risk
      and high-risk leukemia cases, whereas the HLA-C mismatch or HLA-class II (DRB1
      and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus
      was found to reduce survival in leukemia cases. Thus, the role of the HLA class I
      allele in unrelated bone marrow transplantation was elucidated. Notably, HLA-C
      alleles had a different mode from HLA-A or -B alleles for acute GVHD and
      survival.

PMID- 12010827
TI  - Donor-derived interferon gamma separates graft-versus-leukemia effects and graft
      versus-host disease induced by donor CD8 T cells.
AB  - The graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD)
      inducing activity of CD8 T cells was compared in murine recipients of wild-type
      (WT) or interferon gamma (IFN-gamma)-deficient (GKO) allogeneic donor cells. CD8
      T cells (or CD4-depleted splenocytes) from GKO donor mice induced more severe
      GVHD in lethally irradiated allogeneic recipients compared to the same cell
      populations from WT donors. Consistent with GVHD severity, donor CD8 T-cell
      expansion in allogeneic recipients was augmented in the absence of IFN-gamma.
      These results demonstrate that IFN-gamma does not stimulate but instead down
      modulates GVHD induced by donor CD8 T cells. Remarkably, antihost
      lymphohematopoietic reactions, including GVL effects against host
      leukemia/lymphoma cells, of CD8 T cells correlated inversely with their GVHD
      inducing activity, and those of GKO donors were markedly weaker than those
      mediated by WT donor CD8 T cells. These data show for the first time that GVHD
      inducing activity and GVL effects of allogeneic CD8 T cells can be separated by a
      single cytokine, IFN-gamma. (Blood. 2002;99:4207-4215)

PMID- 12010828
TI  - Relationship between glutathione S-transferase M1, T1, and P1 polymorphisms and
      chronic lymphocytic leukemia.
AB  - Interindividual differences in susceptibility to hematologic malignancies may be
      mediated in part through polymorphic variability in the bioactivation and
      detoxification of carcinogens. The glutathione S-transferases (GSTs) have been
      implicated as susceptibility genes in this context for a number of cancers. The
      aim of this study was to examine whether polymorphic variation in GSTs confers
      susceptibility to chronic lymphocytic leukemia (CLL). GSTM1, GSTT1, and GSTP1
      genotypes were determined in 138 patients and 280 healthy individuals. The
      frequency of both GSTM1 and GSTT1 null genotypes and the GSTP1-Ile allele was
      higher in cases than in controls. There was evidence of a trend in increasing
      risk with the number of putative "high-risk" alleles of the GST family carried (P
      =.04). The risk of CLL associated with possession of all 3 "high-risk" genotypes
      was increased 2.8-fold (OR = 2.8, 95% confidence interval: 1.1-6.9). Our findings
      suggest that heritable GST status may influence the risk of developing CLL.

PMID- 12010829
TI  - Interaction of calmodulin with the cytoplasmic domain of platelet glycoprotein
      VI.
AB  - The platelet collagen receptor, glycoprotein VI (GPVI), and GPIb-IX-V, which
      binds von Willebrand factor, initiate platelet aggregation at low or high shear
      stress, respectively. We recently reported that positively charged, membrane
      proximal sequences within cytoplasmic domains of GPIbbeta and GPV of GPIb-IX-V
      bind calmodulin. We now show that GPVI also binds calmodulin as follows-(1)
      calmodulin coimmunoprecipitated with GPVI from resting platelet lysates using an
      anti-GPVI IgG, but partially dissociated in platelets activated by collagen or
      collagen-related peptide; (2) calmodulin coprecipitated from platelet lysates
      with maltose-binding protein (MBP)-GPVI cytoplasmic domain fusion protein, but
      not MBP alone; (3) GPVI-related synthetic peptide based on the membrane-proximal
      sequence, His269-Pro287, induced a shift in calmodulin migration on nondenaturing
      gels, an assay that identifies calmodulin-binding peptides. His269-Pro287 is
      analogous to the calmodulin-binding sequence in GPIbbeta. The novel interaction
      of GPVI and calmodulin may regulate aspects of GPVI function.

PMID- 12010830
TI  - Experience with gemtuzumab ozogamycin ("mylotarg") and all-trans retinoic acid in
      untreated acute promyelocytic leukemia.
AB  - We administered gemtuzumab ozogamycin ("mylotarg"; 9 mg/m(2) day 1 or 5) and all
      trans retinoic acid (ATRA) to 19 patients with untreated acute promyelocytic
      leukemia (APL). There were 3 patients who also received idarubicin because of a
      white blood cell (WBC) count of more than 30 000/microL. In complete remission
      (CR), patients were to receive 8 courses of mylotarg (9 mg/m(2) every 4 to 5
      weeks) and ATRA; idarubicin was added only for persistent or recurrent polymerase
      chain reaction (PCR) positivity. The CR rate was 16/19 (84%). All 12 patients
      tested to date were PCR-negative 2 to 4 months from CR date; none of the 7
      patients evaluated subsequently have reverted to PCR positivity (median follow-up
      in CR was 5 months, up to 14 months). Mylotarg was well tolerated. A median of 5
      post-CR courses have been given to date with 3 patients having currently received
      8 post-CR courses, and 4 patients receiving 7 post-CR courses. Mylotarg appears
      active in APL, and repeated administration is feasible.

PMID- 12010831
TI  - Relationship of CD8(+) T cell noncytotoxic anti-HIV response to CD4(+) T cell
      number in untreated asymptomatic HIV-infected individuals.
AB  - During chronic HIV infection, asymptomatic individuals demonstrate a strong
      CD8(+) cell noncytotoxic antiviral response (CNAR). With the onset of symptoms or
      reduction in CD4(+) cell counts, CNAR decreases. Presently, it is recommended
      that infected individuals receive antiretroviral therapy if CD4(+) cell counts
      fall below 350 cells/microL. To determine whether CNAR lends support to this
      recommendation for initiation of antiretroviral treatment, we examined CNAR in 20
      healthy, untreated, HIV-infected men exhibiting a range of CD4(+) cell numbers.
      Our results indicate that the asymptomatic untreated HIV-infected individuals
      with less than 300 CD4(+) cells/microL had a significantly lower CNAR than those
      with higher CD4(+) cell counts. These data on CNAR in untreated, healthy, HIV
      infected individuals support the current recommendation for when to initiate
      antiretroviral therapy.

PMID- 12010832
TI  - Measurement of spleen volume by ultrasound scanning in patients with
      thrombocytosis: a prospective study.
AB  - Spleen size was assessed in 73 patients with thrombocytosis and in 15 healthy
      subjects, comparing palpation with ultrasonography (US) measurement of
      longitudinal diameter and volume. Intraobserver and interobserver variability for
      volume on US, checked in 12 patients, was very low. Correlation between spleen
      volume measured by US and that measured by computed tomography was excellent.
      Splenomegaly was detected by palpation in 25% of patients, by US assessment of
      longitudinal diameter in 33%, and by US assessment of volume in 52%. After
      diagnostic work-up, 54 patients had a diagnosis of essential thrombocythemia
      (ET), 4 of idiopathic myelofibrosis (IMF), and 15 of secondary thrombocytosis
      (ST). Spleen volume in patients with ST was in the normal range (138 +/- 47 mL)
      and was significantly lower than that in patients with ET or IMF (370 +/- 210 mL;
      P <.001). Thus, US-measured volume was the most sensitive method for identifying
      nonpalpable splenomegaly in patients with primary myeloproliferative diseases,
      and it may help in distinguishing these diseases from reactive disorders.

PMID- 12010833
TI  - Molecular basis of NB1 (HNA-2a, CD177) deficiency.
AB  - Alloimmunization to the neutrophil antigen NB1 (HNA-2a, CD177) can result in
      immune neutropenia and transfusion-related acute lung injury. Recently, we were
      able to elucidate the primary structure of NB1. To shed light also on the
      molecular basis of the NB1-negative phenotype, we studied the neutrophils of 2
      women with NB1-specific alloantibodies for intracellular and extracellular NB1
      expression, NB1-specific mRNA production, and the presence of the NB1 gene. No
      antibody binding to neutrophils was observed by immunofluorescence and immunoblot
      using a variety of human and monoclonal NB1-specific antibodies. By reverse
      transcription-polymerase chain reaction with NB1-specific primers we could not
      detect NB1 cDNAs without accessory sequences, which were found to be introns. The
      NB1 gene was present in the genome of both patients. Our data indicate that the
      NB1-negative phenotype is the result of different off-frame insertions on RNA
      level, resulting in NB1 deficiency on neutrophils.

PMID- 12010834
TI  - Nonmyeloablative conditioning followed by hematopoietic cell allografting and
      donor lymphocyte infusions for patients with metastatic renal and breast cancer.
AB  - The feasibility and toxicity of allogeneic stem cell transplantation after
      nonmyeloablative conditioning including thiotepa, fludarabine, and
      cyclophosphamide have been investigated in 6 patients with breast cancer and 7
      patients with renal cell cancer. The program included the use of escalating doses
      of donor lymphocyte infusions (DLI) and/or interferon alpha (IFNalpha) for
      patients showing no tumor response and no graft-versus-host disease (GVHD).
      Patients were at high risk of transplant-related mortality (TRM) because of age,
      advanced stage, and previous treatments. We observed a partial remission in 4
      renal cancer and in 2 breast cancer patients (one at the molecular level in the
      bone marrow), occurring after cyclosporine withdrawal or after DLI and/or
      IFNalpha. All the responses were accompanied by the occurrence of acute GVHD. We
      conclude that reduced-intensity allogeneic stem cell transplantation is a
      feasible procedure in renal and breast cancer, and that the exploitation of graft
      versus-tumor effect after DLI is a promising finding.

PMID- 12010835
TI  - Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on
      sensitivity to acenocoumarol.
AB  - The 2C9*3 and 2C9*2 polymorphisms of cytochrome P-450 CYP2C9 are associated with
      hypersensitivity to warfarin and bleeding. The effect of these polymorphisms on
      sensitivity to acenocoumarol is unknown. Three groups of patients, with low,
      medium, or high acenocoumarol-dose requirements, were studied. Age influenced the
      acenocoumarol sensitivity. Bearing the 2C9*3 allele was associated with the need
      for a lower acenocoumarol dose (odds ratio [OR], 6.02; 95% confidence interval
      [CI], 1.50-24.18); 80% of carriers of the 2C9*3 allele required a low dose. The
      2C9*2 allele was associated with a lower acenocoumarol-dose requirement (OR,
      2.70; 95% CI, 1.11-6.58) because of a reduced risk of the need for a high
      acenocoumarol dose (4.8% of the patients in the high-dose group carried the 2C9*2
      allele versus 34.1% and 30.2%, respectively, in the medium-dose and low-dose
      groups). Therefore, carriers of 2C9*3 may need a low initial loading dose of
      acenocoumarol. Because acenocoumarol sensitivity with the 2C9*2 variant does not
      seem to be clinically relevant, the drug could be an alternative to warfarin in
      2C9*2 carriers.

PMID- 12010836
TI  - Prospective study of hepatitis C viral infection as a risk factor for subsequent
      B-cell neoplasia.
AB  - Several case-control studies have found increased prevalence of hepatitis C virus
      (HCV) in patients with non-Hodgkin lymphoma (NHL) and other B-cell
      lymphoproliferative disorders. We examined whether HCV infection preceded the
      development of these neoplasms in a prospective cohort study of 48 420
      individuals in northern California. Stored sera from 95 subjects with NHL (n =
      57), multiple myeloma (n = 24), or Hodgkin disease (n = 14) diagnosed a mean of
      21 years after phlebotomy were screened for antibodies to HCV as well as viral
      RNA, based on previous reports of antibody-negative viremia. Sera from 4 cases
      and one of 95 age-, sex-, and race-matched controls were repeatedly reactive by
      enzyme immunoassay, but none were confirmed by recombinant immunoblot assay; none
      of the case sera had HCV RNA by reverse transcription- polymerase chain reaction.
      Although acquisition in later life cannot be ruled out, these prospective data do
      not support a substantial role of chronic HCV infection in the etiology of B-cell
      neoplasia.

PMID- 12010837
TI  - COPD in 2001: a major challenge for medicine, the pharmaceutical industry, and
      society.

PMID- 12010838
TI  - COPD in perspective.
AB  - In the last 200 years or so, the recognition, diagnosis, and understanding of the
      pathogenesis of COPD have evolved considerably. Over the past few decades,
      various definitions of COPD and its "components" also have developed. Despite
      this, however, the treatment options for patients with this relentlessly
      progressive disorder are relatively limited. In the mid-19th century, the
      introduction of the spirometer yielded a powerful tool for the diagnosis of COPD.
      The currently available small, cheap spirometers hold great promise to help
      patients and their physicians closely monitor lung function. Early recognition of
      the close associations among emphysema and, more recently, small airways disease,
      and impaired airflow is discussed. This review also stresses the importance of
      the identification of COPD in its initial stages and the early onset of
      appropriate treatment. The therapy for COPD has changed in the last 40 years.
      Drug therapies in the 1960s included potassium iodide and ephedrine.
      Corticosteroids were not used, and oxygen therapy and exercise were actually
      contraindicated. Modern therapy for COPD is now more systematic and includes the
      use of bronchodilators and corticosteroids to improve airflow, in addition to
      oxygen therapy, pulmonary rehabilitation and, in selected patients, lung volume
      reduction surgery. The causal link between the chronic inhalation of tobacco
      smoke and COPD is beyond doubt, and smoking cessation remains the most important
      goal for patients. It is hoped that new, more effective therapies will soon be
      available for the treatment of this disabling disorder to provide improvement in
      symptoms and patient quality of life and to reduce or stop the rate of disease
      progression and mortality in patients with COPD.

PMID- 12010839
TI  - COPD: epidemiology, prevalence, morbidity and mortality, and disease
      heterogeneity.
AB  - COPD continues to cause a heavy health and economic burden both in the United
      States and around the world. Some of the risk factors for COPD are well-known and
      include smoking, occupational exposures, air pollution, airway
      hyperresponsiveness, asthma, and certain genetic variations, although many
      questions, such as why < 20% of smokers develop significant airway obstruction,
      remain. Precise definitions of COPD vary and are frequently dependent on an
      accurate diagnosis of the problem by a physician. These differences in the
      definition of COPD can have large effects on the estimates of COPD in the
      population. Furthermore, evidence that COPD represents several different disease
      processes with potentially different interventions continues to emerge. In most
      of the world, COPD prevalence and mortality are still increasing and likely will
      continue to rise in response to increases in smoking, particularly by women and
      adolescents. Resources aimed at smoking cessation and prevention, COPD education
      and early detection, and better treatment will be of the most benefit in our
      continuing efforts against this important cause of morbidity and mortality.

PMID- 12010840
TI  - Systemic effects in COPD.
AB  - The pathogenesis and clinical manifestations of COPD are not restricted to
      pulmonary inflammation and structural remodeling. Rather, this disorder is
      associated with clinically significant systemic alterations in biochemistry and
      organ function. The systemic aspects of COPD include oxidative stress and altered
      circulating levels of inflammatory mediators and acute-phase proteins. Indeed, an
      impaired endogenous oxidant-antioxidant balance has been reported in patients
      experiencing exacerbations of COPD, and others have observed altered circulating
      levels of several cytokines and adhesion molecules in patients with stable
      disease. As in other chronic inflammatory conditions, weight loss, muscle
      wasting, and tissue depletion are commonly seen in COPD patients. Selective
      wasting of fat-free mass coupled with impaired respiratory and peripheral muscle
      function and a reduced capacity for exercise occur in COPD patients. Indeed,
      weight loss may directly impact poor prognosis in COPD patients. The mechanisms
      underlying weight loss and muscle wasting are incompletely understood but likely
      involve an imbalance in ongoing processes of protein degradation and replacement.
      This may include alterations in the relative levels or activities of endocrine
      hormones such as insulin, growth hormone, testosterone, and glucocorticoids.
      Furthermore, chronic systemic inflammation involving cytokines such as
      interleukin-1 and tumor necrosis factor-alpha may be associated with these
      hormonal changes and muscle wasting in COPD patients. This review includes a
      discussion of the mechanisms of skeletal muscle fiber protein
      metabolism/catabolism, the potential roles of endogenous cytokines in protein
      loss, and the possibility that novel drugs that inhibit cytokine signaling may
      provide benefits by reducing muscle wasting and cachexia, thereby improving the
      prognosis and quality of life among COPD patients.

PMID- 12010841
TI  - Muscle metabolism and exercise tolerance in COPD.
AB  - This article explores the hypothesis that dyspnea in patients with COPD arises
      from an imbalance between the load placed on the respiratory muscle pump and its
      capacity. Evidence to support this concept is presented, and possible therapeutic
      approaches are discussed.

PMID- 12010842
TI  - Exacerbations: etiology and pathophysiologic mechanisms.
AB  - Some patients with COPD are prone to frequent exacerbations, which are an
      important determinant of health status. Such patients have elevated airway
      cytokine levels, suggesting the presence of increased inflammation that may
      increase their susceptibility to exacerbation. The inflammatory response during a
      COPD exacerbation is variable, but increases in interleukin-6 levels during the
      exacerbation are related to the presence of a common cold. Rhinovirus infection
      is the most important etiologic factor in COPD exacerbations and is an important
      target for preventive therapy. The reduction of COPD exacerbations will have an
      important impact on the considerable morbidity and mortality associated with
      COPD.

PMID- 12010843
TI  - Airways inflammation and COPD: epithelial-neutrophil interactions.
AB  - Neutrophils are recognized as major cellular mediators of inflammation. They
      contain specific and highly regulated mechanisms for controlling the expression
      of adhesion molecules that allow for their tethering and migration into
      inflammatory sites. These adhesion molecules not only are activated by exogenous
      pollutants but are regulated by endothelial and epithelial cell signals. Lipid
      mediators, such as platelet-activating factor, reactive oxygen and nitrogen
      species, and cytokines from airway epithelial cells, further control neutrophil
      functions such as infiltration and activation resulting in an increase in
      respiratory burst activity and release of granule enzymes, such as elastase.
      Furthermore, virus and bacteria products affect inflammation by increasing
      secondary epithelial mediators. However, once the endogenous or exogenous agents
      are expelled, neutrophil populations are programmed to die and are cleared by
      macrophage phagocytosis.

PMID- 12010844
TI  - Neutrophils and the pathogenesis of COPD.

PMID- 12010845
TI  - Macrophages and the pathogenesis of COPD.
AB  - Macrophages are long-lived effector cells within the lung. They are reactive,
      responding to endogenous and exogenous stimuli, as well as proactive, producing
      mediators that modulate the behavior of surrounding cells. In addition, they play
      a critical role in the clearance of apoptotic neutrophils. Their role in COPD
      probably reflects a number of functional properties. However, if the link between
      increased proteinase burden and tissue destruction and injury in patients with
      COPD is correct, then macrophages must be very significant. Even though other
      cells, including epithelial cells and fibroblasts, have been shown to express
      higher matrix metalloproteinase (MMP) levels in lung tissue from subjects with
      COPD and emphysema, the numbers of resident cells do not appear to increase by
      the same factor as that of sequestered macrophages. The combination of a 5- to 10
      fold increase in macrophage numbers, the up-regulation of MMPs, and their co
      release with other classes of stored proteinases must be highly significant in
      terms of an increase in proteinase potential in the small airways and respiratory
      units. This may account for increased tissue destruction and inflammatory
      mediator activation leading to the pathology that occurs during COPD. Since only
      about 15% of smokers develop clinically significant disease, it seems likely, in
      smokers without COPD, that these processes either are strictly controlled or that
      lung repair mechanisms are more effective.

PMID- 12010846
TI  - Inflammation of the airways and lung parenchyma in COPD: role of T cells.
AB  - A smoking-induced inflammatory reaction in the airways and lung parenchyma,
      comprised mainly of neutrophils and alveolar macrophages, has long been accepted
      to be the major cause of COPD in smokers. Recent reports have underlined the role
      of the T lymphocyte as a potentially important factor in the inflammatory process
      leading to COPD. It has been found that, in the airways and the lung parenchyma,
      the presence of T cells, predominantly CD8+ T cells, can distinguish between
      smokers with and without COPD. In addition to T cells, other inflammatory cell
      types such as neutrophils and macrophages are probably essential in the initial
      inflammatory process leading to the breakdown of lung tissue, perhaps producing
      peptides eventually recognized by T cells as antigenic. This would provide an
      explanation for the T-cell inflammation. Once activated, T cells are present in
      the lung, and their effector functions would include the attraction and
      enhancement of the inflammatory function in other inflammatory cells like
      neutrophils and macrophages. It seems likely that, only when all inflammatory
      cell types (ie, CD4+, CD8+, neutrophils, and macrophages) are present in the
      lung, the airways remodeling and parenchymal destruction characteristic of COPD
      will ensue. If T cells are responsible for the lung injury and progression of
      COPD, it would resemble a response to an antigenic stimulus originating in the
      lung. If that were the case, COPD could be considered to be an autoimmune disease
      triggered by smoking.

PMID- 12010847
TI  - Mucin apoprotein expression in COPD.
AB  - Mucins, which are complex glycoproteins that provide the viscoelastic properties
      of mucus that are essential for the protection of the airways, are characterized
      by a variable-number tandem repeats (VNTR) region that may undergo alternate
      splicing during transcription. Such transcripts may yield multiple proteins via
      diverse post-translational modifications involving glycosylation (within each
      VNTR). Fifteen distinct mucin genes have been identified, with several mapping to
      chromosomal clusters (ie, 7q22 and 11p15.5), possibly having evolved by gene
      duplication. The deduced protein sequences can be subdivided into both membrane
      associated mucins and secreted mucins. Membrane-associated mucins consist of
      cytoplasmic, transmembrane, and extracellular domains. The membrane-associated
      mucins MUC1, MUC4, and MUC11 have been localized to the lung. In addition to
      VNTRs, secreted mucins possess repeated cysteine-rich D-domains (which are
      important in polymerization). Secreted mucins that are localized to the lung
      include MUC2 (in cells with and without secretory granules), MUC5AC (in surface
      and submucosal mucous cells), MUC5B and MUC8 (in submucosal mucous cells), and
      MUC7 (in submucosal serous cells). Currently, little is known about the
      regulation of mucins in COPD patients. Recent studies with acrolein and cigarette
      smoke have suggested that MUC5AC is inducible (accompanied by epidermal growth
      factor [EGF] ligand formation and the activation of EGF receptor-dependent
      pathways), whereas MUC5B is constitutively expressed (increasing through gland
      enlargement). Similarly, little is known about the genetic determinants that
      control mucus hypersecretion, but preliminary findings in animal models suggest
      that intrastrain differences in acrolein-induced mucin formation are amenable to
      genetic analysis. As our understanding of the functional genomics of mucin
      biology increases, further clinical targets and therapeutic strategies are likely
      to emerge.

PMID- 12010848
TI  - Latent adenovirus infection in COPD.
AB  - We have concentrated on the adenovirus as the source of the heightened
      inflammatory response of the lungs of patients with COPD. We have concentrated in
      particular on the responses to agents such as lipopolysaccharides and
      environmental particulates that contaminate the air we breathe, and we have
      accumulated evidence that the E1A gene of this virus could be the key player in
      this process. As other intracellular pathogens such as Chlamydia pneumoniae have
      recently been implicated in the pathogenesis of COPD, our studies on the
      adenovirus E1A could serve as the model for investigating the interaction between
      host and extrinsic factors in the chronic progression of this debilitating lung
      disease.

PMID- 12010849
TI  - A model of tobacco smoke-induced airflow obstruction in the guinea pig.
AB  - Animal models have proven to be extremely worthwhile in the investigations of
      cigarette smoke-induced lung disease. We have found the guinea pig to be useful,
      with a large number of advantages and few disadvantages when used in our
      experimental circumstances. Other animal models exist, however, and the
      investigator should select the model that is most suited to the hypothesis to be
      tested.

PMID- 12010850
TI  - Phosphodiesterase 4 inhibitors for the treatment of COPD.
AB  - Phosphodiesterase 4 (PDE4) is a major cyclic adenosine-3',5'-monophosphate
      metabolizing enzyme in immune and inflammatory cells, airway smooth muscle, and
      pulmonary nerves. Selective inhibitors of this enzyme have been available for a
      number of years and show a broad spectrum of activity in animal models of COPD
      and asthma. The class-associated side effects, mainly nausea and emesis, appear
      to have been at least partially overcome by the so-called "second-generation"
      PDE4 inhibitors. Currently, three companies are in the later stages of
      development of candidate second-generation PDE4 inhibitors for the treatment of
      COPD patients. The preclinical profile of one of these, BAY 19-8004, is
      summarized below. The initial clinical data on the most advanced compound,
      cilomilast, were indeed encouraging. However, full knowledge of the therapeutic
      value of this novel compound class awaits the outcome of longer term clinical
      trials.

PMID- 12010851
TI  - 5-lipoxygenase inhibitors for the treatment of COPD.
AB  - The potential for leukotrienes as mediators to target in the development of novel
      therapies for diseases such as COPD is underscored by their inflammatory behavior
      and the capacity of leukotriene receptor antagonists and synthesis inhibitors to
      reduce inflammatory responses when administered in vivo. Airway neutrophilia in
      COPD patients is believed to be a contributing source of inflammation and is
      associated with airway remodeling. The presence of neutrophils is mediated in
      part by leukotriene B(4) (LTB(4)), and the capacity for LTB(4) alone to replicate
      many aspects of neutrophilic inflammation has provided the focus of drug
      development toward its specific antagonism. More recently, the potential
      involvement of the monocyte-macrophage lineage in the etiology of COPD has
      received growing attention as a target for leukotriene inhibition. The future
      avenues for exploration of leukotriene inhibition could have been expanded by the
      realization that 5-lipoxygenase activity is primarily located at the nuclear
      membrane and the existence of differing cell surface and nuclear receptors to
      LTB(4). The success of compounds under development in this and other anti
      inflammatory classes, however, depends as much on the evolution of clinical
      studies designed to test the "proof of concept" in efficacy through the
      examination of surrogate markers or physiologic readouts of changes in lung
      function.

PMID- 12010852
TI  - P2Y(2) receptor agonists: a new class of medication targeted at improved
      mucociliary clearance.
AB  - Chronic bronchitis is in part characterized by mucus hypersecretion and the
      inability to clear airways of mucus. Despite years of research in this area, to
      date there are no pharmacologic therapies available to enhance or promote
      mucociliary clearance. P2Y(2) receptor agonists are a new class of mucoactive
      compounds that are currently under development for this purpose. This article
      will review the pharmacology of P2Y(2) receptor agonists, review the clinical
      studies performed to date, and highlight the challenges inherent in the
      development of therapies with these pharmacologic properties.

PMID- 12010853
TI  - Contributions of retinoids to the generation and repair of the pulmonary
      alveolus.
AB  - COPD is associated with a progressive, irreversible decline in pulmonary
      function. This is caused in large part by emphysema, the ongoing inflammatory
      destruction of the alveoli and increased airspace size, loss of lung elastic
      recoil, and hyperinflation. The discovery of novel drugs that can reduce the rate
      of lung destruction and airflow limitation, or even stop or reverse the
      underlying processes remains a "holy grail" for the therapy of this disorder.
      Recent reports that retinoic acid markedly ameliorates the emphysema induced in
      rats by administration of elastase have sparked considerable interest in
      retinoids and other alveolar morphogens as potential therapeutic agents. This
      review focuses on mechanisms involved in mammalian alveolar formation, which
      occurs mainly after birth. Roles of endogenous retinoids on pulmonary structural
      cell (epithelial and mesenchymal cells) differentiation and lung development are
      discussed. Also discussed are lung development and structural studies in mice
      that are genetically altered with respect to the expression of subtypes of
      retinoid receptors. Effects of retinoids and other growth factors on elastin gene
      expression and alveolus formation, and the potential pitfalls of drugs that
      interfere with these processes as therapeutic agents are addressed.

PMID- 12010854
TI  - Cytokines and therapy in COPD: a promising combination?
AB  - COPD is a major health problem, with patients showing a progressively declining,
      largely irreversible, change in lung function. This is associated with chronic
      airways inflammation and structural remodeling, including loss of alveolar walls,
      and goblet cell metaplasia with mucus hypersecretion. Inflammatory cells may
      contribute to the airway remodeling via secretion of proteases, fibrotic or
      mitogenic growth factors, and cytokines. In turn, airway remodeling may
      contribute to the clinical symptoms of COPD. Currently available therapies are
      directed to improvement of clinical symptoms and reduction of the airways
      inflammation. The commonly used glucocorticosteroids are expected to reduce the
      inflammation by acting on kinases or transcription factors necessary for
      expression of pro-inflammatory cytokines or chemokines. However, several long
      term and short-term studies showed that glucocorticosteroids are rather
      ineffective in improving lung function and reducing the airway inflammation in
      patients with COPD. New therapeutic strategies may reduce the inflammation and
      alleviate the clinical symptoms of COPD. Tumor necrosis factor-alpha, interleukin
      8, and monocyte chemoattractant protein-1 are important chemotactic proteins for
      macrophages and neutrophils, the predominant inflammatory cells associated with
      COPD. As lung levels of these cytokines are higher in COPD compared to non-COPD
      patients, they may represent targets for novel therapies.

PMID- 12010855
TI  - John Hutchinson's mysterious machine revisited.
AB  - John Hutchinson, a surgeon, recognized that the volume of air that can be exhaled
      from fully inflated lungs is a powerful indicator of longevity. He invented the
      spirometer to measure what he called the vital capacity, ie, the capacity to
      live. Much later, the concept of the timed vital capacity, which became known as
      the FEV(1), was added. Together, these two numbers, vital capacity and FEV(1),
      are useful in identifying patients at risk of many diseases, including COPD, lung
      cancer, heart attack, stroke, and all-cause mortality. This article cites some of
      the rich history of the development of spirometry, and explores some of the
      barriers to the widespread application of simple spirometry in the offices of
      primary care physicians.

PMID- 12010856
TI  - Cancer risk behaviors and screening rates among homeless adults in Los Angeles
      County.
AB  - The homeless encounter many barriers to health care and preventive services,
      while having an increased prevalence of most risk factors for cancer. A group of
      homeless adults (221) at nine different locations within Los Angeles County were
      surveyed during the summers of 1998 and 1999. A portion (71%) reported that they
      had had at least one rectal exam, 42% had a fecal occult blood test, 24% had a
      skin exam, and 23% had an endoscopy (flexible sigmoidoscopy or colonoscopy), and
      of the men aged 50+, only 19% had a prostate-specific antigen test in their
      lifetime. For women aged 40+, 55% had received a Pap smear, and 53% had a breast
      exam, but only 32% had a mammogram within the prior year. Among the sampled
      homeless population, 77% believed in the benefits of cancer screening, 79% were
      not fatalistic about cancer, 63% believed that early detection was efficacious,
      and 83% did not think it would be difficult to get screened. The majority of this
      population demonstrated accurate knowledge of cancer screening guidelines with
      the exception of endoscopy. Cancer screening rates of those surveyed were lower
      than the rates in California for endoscopy, prostate-specific antigen,
      mammography, and Pap smears. Given the lower cancer screening rates compounded by
      higher cancer risk factors, homeless populations need increased access to cancer
      screening tests, as well as education on the availability of free services.
      Additionally, facilities for the homeless and their staff should reinforce the
      purposes of cancer screening, provide more screening services, and implement
      institutional efforts, such as providing nutritious meals and sun protection
      products, to reduce high-risk behaviors and increase further access to cancer
      screening tests.

PMID- 12010857
TI  - The progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of breast
      cancer in Australian women.
AB  - An Alu insertion polymorphism of the progesterone receptor (PR) wasreported
      recently to be associated with a reduced risk of breast cancer, with risks of 0.8
      and 0.3-fold associated with the heterozygote and homozygote genotypes,
      respectively. This intronic variant is considered to be in linkage disequilibrium
      with an exon 4 hinge region G to T Val660Leu polymorphism. We investigated
      whether the exon 4 PR polymorphism was associated with breast cancer in
      Australian women, using a population-based study of 1452 cases and 793 controls,
      half of whom were <40 years of age, and the other half were 40-59 years of age.
      There was no difference in genotype distribution between cases and controls (P =
      0.5) and no evidence of risk associated with either the GT or TT genotypes
      compared with the common GG genotype. The adjusted odds ratios (ORs) were 0.97
      (95% confidence interval, 0.79-1.19) and 1.52 (95% confidence interval, 0.87
      2.66), respectively (P = 0.8 and 0.1), and the results were independent of age
      and family history of breast cancer. Our data provided no support for the
      previously reported decreased risk of breast cancer associated with the T allele,
      with 80% power to detect an OR of 0.8 or less for the heterozygote genotype and
      90% power to detect an OR of 0.3 or less for the rare homozygous TT genotype.
      There was also no support for a greatly increased risk of breast cancer
      associated with the T allele, given that we had 80% power to detect risks of 1.3
      and 2.0 associated with the GT and TT genotypes, respectively. We therefore
      conclude that this polymorphism is not associated with a markedly reduced or
      increased risk of breast cancer in Australian women <60 years of age. However,
      despite its considerable size, our study cannot exclude a small reduced or
      increased risk associated with the T allele, especially the rare TT genotype.

PMID- 12010858
TI  - I105V polymorphism and promoter methylation of the GSTP1 gene in prostate
      adenocarcinoma.
AB  - The GSTP1 gene encodes for an enzyme, glutathione S-transferase pi
      (GSTpi),involved in detoxification of carcinogens. An aminoacid substitution
      (I105V) in GSTP1 produces a variant enzyme with lower activity and less
      capability of effective detoxification. This variant GSTP*B allele has been
      associated with a propensity to develop several neoplasms. Because GSTP1 promoter
      hypermethylation and inactivation of GSTpi expression is a frequent alteration in
      prostate carcinoma, we hypothesized that this somatic epigenetic modification
      could obviate any reduced enzyme activity caused by the germ-line polymorphism.
      We tested for the GSTP1 genotype in a population of prostate cancer patients, and
      in a control group composed of patients with benign prostatic hyperplasia (BPH)
      and healthy blood donors. Tissue samples from the 105 prostate cancer cases (105
      adenocarcinomas and 34 prostatic intraepithelial neoplasia lesions), and from 43
      BPH patients were tested for GSTP1 hypermethylation by methylation-specific PCR.
      GSTpi protein expression was assessed by immunohistochemistry. No significant
      effect on prostate cancer risk was detectable for GSTP1 genotype compared with
      the control population (odds ratio, 1.02; 95% confidence interval, 0.59-1.75).
      Moreover, no association was found between this genotype and tumor or BPH
      methylation status. Patients with unmethylated carcinomas did not disclose
      significant differences in genotypic distribution compared with the control
      population. In adenocarcinoma, a strong association (P < 0.00001) between GSTP1
      promoter hypermethylation and loss of GSTpi expression was observed; however,
      this trend was not retained in prostatic intraepithelial neoplasia or BPH
      lesions. Although the GSTP1 polymorphism is not associated with altered
      susceptibility to prostate cancer, somatic promoter hypermethylation is an
      effective, but not the only, cause of decreased GSTpi function.

PMID- 12010859
TI  - Prospective study of carotenoids, tocopherols, and retinoid concentrations and
      the risk of breast cancer.
AB  - Previous prospective studies have raised the possibility that the
      antioxidantproperties of carotenoids and vitamin E (alpha-tocopherol) and the
      role of vitamin A (retinol) in cellular differentiation may be associated with a
      reduced risk of subsequent breast cancer. To investigate the association between
      serum and plasma concentrations of retinol, retinyl palmitate, alpha-carotene,
      beta-carotene, beta-cryptoxanthin, lutein, lycopene, total-carotenoids, alpha
      tocopherol, and gamma-tocopherol with subsequent development of breast cancer, a
      nested case control study was conducted among female residents of Washington
      County, Maryland, who had donated blood for a serum bank in 1974 or 1989. Cases
      (n = 295) and controls (n = 295) were matched on age, race, menopausal status,
      and date of blood donation, and the analyses were stratified by cohort
      participation. Median concentrations of beta-carotene, lycopene, and total
      carotene were significantly lower in cases compared with controls in the 1974
      cohort (13.1, 12.5, and 7.9% difference; P = 0.01, 0.04, and 0.04, respectively)
      and for lutein in the 1989 cohort (6.7% difference; P = 0.02). The risk of
      developing breast cancer in the highest fifth was approximately half of that of
      women in the lowest fifth for beta-carotene [odds ratio (OR) = 0.41; 95%
      confidence interval (CI) 0.22-0.79; P trend = 0.007], lycopene (OR = 0.55; 95% CI
      0.29-1.06; P trend = 0.04), and total carotene (OR = 0.55; 95% CI 0.29-1.03; P
      trend = 0.02) in the 1974 cohort. There was generally a protective association
      for other micronutrients in both cohorts, although none reached statistical
      significance. The results suggest that carotenoids may protect against the
      development of breast cancer.

PMID- 12010860
TI  - Flavonoids in human urine as biomarkers for intake of fruits and vegetables.
AB  - Flavonoids are polyphenolic compounds ubiquitously found in human diets. We have
      studied the association between urinary excretion of flavonoids and the intake of
      fruits and vegetables to evaluate the usefulness of flavonoids as a biomarker for
      fruit and vegetable intake. Levels of 12 dietary relevant flavonoids were
      determined by LC-MS in urine samples collected prior to an intervention study,
      when the subjects were on their habitual diet (n = 94), and after they had
      participated in an intervention study with diets either high or low in fruits,
      berries, and vegetables (n = 77). Both flavonoid glycosides and aglycones were
      included in the assay, but only the flavonoid aglycones were detectable. Thus,
      the flavonols quercetin, kaempferol, isorhamnetin, and tamarixetin, the
      dihydrochalcone phloretin, and the flavanones naringenin and hesperetin were
      quantified in the enzymatically hydrolyzed urine samples. The habitual intake of
      fruits and vegetables, determined by 3-day dietary records before the
      intervention study, correlated significantly with the total excretion of urinary
      flavonoids, with a coefficient of correlation of 0.35, P < 0.005 (n = 94). In
      addition, highly significant differences in the urinary excretion of all
      flavonoids were observed in the human intervention study between subjects on
      diets high or low in fruits, berries, and vegetables. Also, at the individual
      level a significant positive correlation between changes in fruit and vegetable
      intake and changes in urinary flavonoid excretion was observed. We conclude that
      urinary flavonoids may be useful as a new biomarker for fruit, berry, and
      vegetable intakes and may prove useful when the possible health protective
      effects of flavonoids are studied.

PMID- 12010861
TI  - Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective
      retinoid, LGD1069.
AB  - Retinoids have been used in the clinic for the prevention and treatment of human
      cancers. They regulate several cellular processes including growth,
      differentiation, and apoptosis. Previously, we demonstrated that a pan-agonist
      retinoid 9-cis retinoic acid was able to suppress mammary tumorigenesis in the
      C3(1)-SV40 T-antigen (Tag) transgenic mouse model. However, significant toxicity
      was seen with this naturally occurring retinoid. We hypothesized that the cancer
      preventive effects of retinoids could be dissected from the toxic effects by
      using receptor-selective retinoids. In this study, we used TTNPB, an retinoic
      acid receptor-selective retinoid, and LGD1069, an retinoid X receptor-selective
      retinoid, to preferentially activate retinoic acid receptors and retinoid X
      receptors. In vitro, both compounds were able to inhibit the growth of T47D
      breast cancer cells. We then determined whether these retinoids prevented mammary
      tumorigenesis. C3(1)-SV40 Tag mice were treated daily by gastric gavage with
      vehicle, two different doses of TTNPB (0.3 or 3.0 microg/kg), or two different
      doses of LGD1069 (10 or 100 mg/kg). Mice were treated from approximately 6-8
      weeks to 7-8 months of age. Tumor size and number were measured twice each week,
      and toxicities were recorded daily. Our data show that LGD1069 suppresses mammary
      tumorigenesis in C3(1)-SV40 Tag transgenic mice with no observable toxicity,
      whereas TTNPB had a modest chemopreventive effect, yet was very toxic. Median
      time to tumor development was 129 days in vehicle-treated mice versus 156 days in
      mice treated with 100 mg/kg LGD1069 (P = 0.05). In addition, tumor multiplicity
      was reduced by approximately 50% in mice treated with LGD1069 (2.9 for vehicle,
      2.4 for 10 mg/kg LGD1069, and 1.4 for 100 mg/kg, P < or = 0.03). TTNPB-treated
      mice showed a delayed median time to tumor development (131 days for vehicle
      versus 154 days for 3.0 microg/kg TTNPB; P < or = 0.05), but no changes were seen
      in tumor multiplicity. However, toxicity (skin erythema, hair loss) was seen in
      all of the mice treated with TTNPB. These data demonstrate that receptor
      selective retinoids suppress mammary tumorigenesis in transgenic mice and that
      preventive effects of retinoids can be separated from their toxicity,
      demonstrating that receptor-selective retinoids are promising agents for the
      prevention of breast cancer.

PMID- 12010862
TI  - XRCC1 and CYP2E1 polymorphisms as susceptibility factors of plasma mutant p53
      protein and anti-p53 antibody expression in vinyl chloride monomer-exposed
      polyvinyl chloride workers.
AB  - Mutant p53 protein and anti-p53 antibody in circulating blood can be
      detectedamong individuals with mutations of the p53 tumor suppressor gene. Plasma
      mutant p53 protein and anti-p53 antibody have also been associated with vinyl
      chloride monomer (VCM) exposure, although the mechanism of VCM-related
      carcinogenesis remains unclear. Polymorphisms of metabolic and DNA repair genes
      have been implicated in chemical exposure-related carcinogenesis. The aim of this
      study is to explore the association between polymorphisms of metabolic and DNA
      repair genes with mutant p53 protein and anti-p53 antibody expression induced by
      VCM. Study subjects comprised 333 male workers occupationally exposed to VCM.
      Plasma mutant p53 protein and anti-p53 antibody detected with ELISA were grouped
      together as p53 overexpression. Genotypes of cytochrome P450 2E1 (CYP2E1),
      aldehyde dehydrogenase 2 (ALDH2), glutathione S-transferase T1 (GSTT1), and X-ray
      repair cross-complementing group 1 (XRCC1, exon 10) genes were identified by the
      PCR. High VCM exposure group had significantly higher p53 overexpression as
      compared with low exposure group [odds ratio (OR), 2.1; 95% confidence interval
      (CI), 1.1-3.8]. Individuals having experienced a high VCM exposure and displaying
      a XRCC1 Gln-Gln genotype had a highest risk of p53 overexpression among those
      having different combinations of VCM exposure and XRCC1 genotypes (OR, 6.5; 95%
      CI, 1.7-24.2). Interestingly, those subjects reflecting a CYP2E1 c2c2 genotype
      among the low VCM-exposure group demonstrated a greater risk of p53
      overexpression (OR, 9.8; 95% CI, 1.2-81.6) as compared with those experiencing a
      low VCM exposure and CYP2E1 c1c1/c1c2 genotypes. Additional analysis revealed
      that individuals possessing more susceptible XRCC1 Gln-Gln, CYP2E1 c2c2, ALDH2 1
      2/2-2, and non-null GSTT1 genotypes were more likely to reveal p53
      overexpression. Our results suggest that susceptible XRCC1 and CYP2E1 genotypes
      may modulate the mutation of the p53 gene among VCM-exposed workers.

PMID- 12010863
TI  - Regression of cervical intraepithelial neoplasia and loss of human papillomavirus
      (HPV) infection is associated with cell-mediated immune responses to an HPV type
      16 E7 peptide.
AB  - Most human papillomavirus (HPV)-associated cervical intraepithelial
      neoplasia(CIN) lesions in normal women regress spontaneously, but a small number
      persist and may progress to invasive cancer. To evaluate the role of immunity to
      HPV and the outcome of CIN and associated HPV infection, we examined cell
      mediated immune (CMI) responses to HPV 16 E6 and E7 peptides. One hundred thirty
      six women with biopsy-confirmed CIN I or CIN II were followed for 1 year at 3
      month intervals. Study subjects were 58% Hispanic, 36% African American, and 6%
      of other ethnicity, and were attending a municipal hospital colposcopy clinic. At
      each visit, cervical cytology and cervicovaginal lavage for HPV detection and
      typing was done, and blood was obtained for immunological studies.
      Lymphoproliferative CMI responses to HPV 16 E6 and E7 peptides were tested. An
      end point biopsy was done after the 1-year follow-up. The association between CMI
      responses to specific peptides and the outcome of disease was evaluated. CMI
      responses to E7 peptide (37-54) correlated significantly with regression of
      disease and with resolution of viral infection within 12 months. The protective
      effects of CMI to this peptide were not HPV type-specific. CMI responses to
      several other peptides also showed an association with regression, although not
      significant at present sample size. E7 peptide 37-54 contains one or more human T
      cell epitopes. Identification and mapping of "protective" epitopes in the HPV E6
      and E7 proteins could lead to the development of immunological assays to
      determine the risk of CIN and the development of immunotherapeutic protocols for
      the management of premalignant and malignant HPV-associated neoplasia and,
      ultimately, for the prevention of cancer.

PMID- 12010864
TI  - Association of CYP1B1 polymorphisms and breast cancer risk.
AB  - Cytochrome P450 1B1 catalyzes the conversion of 17-beta-estradiol (E2) to
      thecatechol estrogen metabolites 2-OH-E2 and 4-OH-E2 that have been postulated to
      be involved in mammary carcinogenesis. We sought to determine whether two common
      functional polymorphisms in Cytochrome P450 1B1, V432L (m1), and A453S (m2) are
      related to breast cancer risk. Using a nested case control design within the
      Nurses' Health Study cohort, we genotyped 453 cases and 456 controls and found no
      significant association between m1[val/leu and leu/leu versus val/val, OR = 1
      (CI, 0.72-1.45)] or m2 [asn/ser and ser/ser versus asn/asn, OR = 0.8 (CI, 0.62
      1.15)] and breast cancer risk. However, we did observe women with the Val/Val
      (m1) genotype to have a higher percentage of estrogen receptor-positive tumors (P
      = 0.03). We did not observe any correlation with the m2 genotypes and estrogen
      receptor status. The association of the m1 and m2 genotypes on plasma hormone
      levels in postmenopausal control women not using hormone replacement therapy was
      also evaluated. Carriers of the m1 leu and m2 ser alleles had modestly higher
      estradiol levels but similar estrone and estrone sulfate levels. The results
      presented do not support a strong association between m1 and m2 and the risk of
      breast cancer.

PMID- 12010865
TI  - Factors associated with refusal to provide a buccal cell sample in the
      Agricultural Health Study.
AB  - Epidemiological studies are increasingly collecting buccal cells and other
      sources of DNA for genetic analysis. However, high refusal rates raise concerns
      about possible selection bias. This study examines the subject characteristics
      associated with refusal or failure to provide a buccal cell sample. Subjects were
      male farmers in the Agricultural Health Study, which is being conducted in Iowa
      and North Carolina. As part of a 5-year follow-up, cohort members were contacted
      by telephone and asked to participate in a telephone interview and to consent to
      providing a buccal cell sample using a kit that was mailed to them. Demographic,
      lifestyle, disease, and occupational characteristics were compared between
      consenters who returned a sample ("compliers"), nonconsenters ("refusers"), and
      consenters who failed to return a sample ("noncompliers"). Compliers (n = 8794),
      refusers (n = 3178), and noncompliers (n = 3008) were quite similar, although
      compliers tended to be slightly older. Although some significant differences
      between these groups were observed, the magnitude of these differences was
      generally small, usually no more than a few percentage points. In conclusion,
      this study found little difference between male farmers who agreed to provide
      buccal cell samples versus those who either refused to provide a sample or who
      agreed but failed to return the sample. Observed differences were typically small
      and would be unlikely to compromise etiologic associations identified in such a
      prospective study. In short, there appears to be little selection bias in the
      Agricultural Health Study buccal cell collection process, further supporting the
      use of such mailed collection kits in epidemiological research.

PMID- 12010866
TI  - A polymorphism in the UDP-Glucuronosyltransferase 2B15 gene (D85Y) is not
      associated with prostate cancer risk.

PMID- 12010867
TI  - Correspondence re: Samowitz et al., Microsatellite instability in sporadic colon
      cancer is associated with an improved prognosis at the population level. Cancer
      Epidemiol. Biomark. Prev., 10: 917-923, 2001.

PMID- 12010869
TI  - Primary biliary cirrhosis: seeking the silent partner of autoimmunity.
AB  - Primary biliary cirrhosis is a disorder characterised by an intense inflammatory
      response in the septal and interlobular bile ducts and is considered to be an
      autoimmune disease. Evidence to suggest that chronic viral infection could be a
      crucial element in the development of biliary epithelial cell damage and
      activation of the associated autoimmune response is reviewed

PMID- 12010870
TI  - Easy as 1, 2, 3? Histamine receptors and gastric acid.

PMID- 12010871
TI  - UGT1A1 polymorphisms and colorectal cancer susceptibility.

PMID- 12010872
TI  - HCC: what's the score.

PMID- 12010873
TI  - Does chemoradiotherapy after intended curative surgery increase survival of
      gastric cancer patients?

PMID- 12010874
TI  - Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small
      intestine and colon.
AB  - BACKGROUND AND AIMS: In order to establish whether extraintestinal cells
      contribute to the turnover and repair of gastrointestinal tissues, we studied the
      colons and small intestines of female mice that had received a male bone marrow
      transplant, together with gastrointestinal biopsies from female patients that had
      developed graft versus host disease after receiving a bone marrow transplant from
      male donors. METHODS: Using in situ hybridisation to detect Y chromosomes and
      immunohistochemistry, we demonstrated that cells derived from injected bone
      marrow frequently engrafted into the intestine and differentiated into
      pericryptal myofibroblasts. RESULTS: In the human intestine, we confirmed by
      combining in situ hybridisation with immunostaining for smooth muscle actin that
      the bone marrow derived cells within the intestine exhibited a myofibroblast
      phenotype. In female mouse recipients of male bone marrow grafts, we observed
      colocalisation of Y chromosomes and clusters of newly formed marrow derived
      myofibroblasts. While few of these were present at seven days after bone marrow
      transplantation, they were numerous at 14 days, and by six weeks entire columns
      of pericryptal myofibroblasts could be seen running up the sides of crypts in
      both the small intestine and colon. These columns appeared to extend into the
      villi in the small intestine. Within the intestinal lamina propria, these Y
      chromosome positive cells were negative for the mouse macrophage marker F4/80
      antigen and CD34. CONCLUSIONS: Bone marrow derived pericryptal myofibroblasts
      were present in the mouse intestine following irradiation and bone marrow
      transplant, and in the intestines of human patients suffering graft versus host
      disease following a bone marrow transplant. Our data indicate that bone marrow
      cells contribute to the regeneration of intestinal myofibroblasts and epithelium
      after damage, and we suggest that this could be exploited therapeutically.

PMID- 12010875
TI  - Effect of sildenafil on oesophageal motor function in healthy subjects and
      patients with oesophageal motor disorders.
AB  - BACKGROUND AND AIMS: Sildenafil blocks phosphodiesterase type 5 which degrades
      nitric oxide (NO) stimulated 3'5'-cyclic monophosphate (cGMP), thereby relaxing
      smooth muscle cells in various organs. We used sildenafil as a tool to
      investigate the role of the NO-cGMP pathway in the oesophagus of healthy
      volunteers and patients with hypercontractile oesophageal motility disorders.
      METHODS: Six healthy male volunteers participated in a randomised double blind
      study on two separate days before and one hour after oral intake of either
      sildenafil 50 mg or placebo. Oesophageal manometry was performed to determine
      vector volume of the lower oesophageal sphincter (LOS) and pressure amplitudes of
      the oesophageal body. Four of the volunteers underwent 12 hour ambulatory
      oesophageal manometry on two separate days, once with sildenafil 50 mg and once
      with placebo. An activity index for spontaneous swallowing was calculated for
      every hour of the study. Eleven patients with hypercontractile oesophageal
      motility disorders took part in an open study of the effect of 50 mg sildenafil
      on manometric features of their disorder and on the clinical response to
      sildenafil taken as required. RESULTS: In healthy subjects, sildenafil
      significantly reduced LOS pressure vector volume and pressure amplitudes in the
      distal half of the oesophageal body. In three of four subjects the inhibitory
      effect of sildenafil lasted at least eight hours. In nine of 11 patients,
      manometric improvement after sildenafil was observed but only four had an
      improvement in oesophageal symptoms with sildenafil taken as required. Two of
      these four patients however experienced side effects and did not want to continue
      treatment. CONCLUSIONS: Sildenafil lowers LOS pressure and propulsive forces in
      the body of the oesophagus of healthy subjects as well as in patients with
      nutcracker oesophagus, hypertensive LOS, and achalasia. The effect of sildenafil
      on the oesophageal body may last for up to eight hours in healthy volunteers. A
      subset of patients with hypertensive LOS or nutcracker oesophagus may benefit
      from sildenafil but side effects are a limiting factor.

PMID- 12010876
TI  - Timed barium oesophagram: better predictor of long term success after pneumatic
      dilation in achalasia than symptom assessment.
AB  - BACKGROUND: Symptom relief post pneumatic dilation is traditionally used to
      assess treatment success in achalasia patients. Recently, we showed that symptom
      relief and objective oesophageal emptying are concordant in about 70% of
      patients, while up to 30% of achalasia patients report near complete symptom
      relief despite poor oesophageal emptying of barium. AIMS: We now report the
      results of long term clinical follow up in these two groups of achalasia
      patients, assessing differences in symptomatic remission rates. METHODS:
      Achalasia patients undergoing pneumatic dilation since 1995 were evaluated both
      symptomatically and objectively at regular intervals. Pre and post dilation
      symptoms were recorded. Barium column height was measured five minutes after
      ingesting a fixed volume of barium per patient to assess oesophageal emptying.
      Patients who initially reported near complete symptom relief were divided into
      two groups based on objective findings on barium study: (1) complete oesophageal
      emptying (concordant group), and (2) poor oesophageal emptying (discordant
      group). Patients were followed prospectively for symptom recurrence. RESULTS:
      Thirty four patients with complete symptom relief post pneumatic dilation were
      identified. In 22/34 (65%) patients, the degree of symptom and barium height
      improvements was similar (concordant group). In 10/34 (30%) patients, there was <
      50% improvement in barium height (discordant group). Significantly (p<0.001) more
      discordant (9/10; 90%) than concordant (2/22; 9%) patients failed therapy at the
      one year follow up. Seventeen of 22 (77%) concordant patients were still in
      remission while all discordant patients had failed therapy by six years of follow
      up. Length of time in symptom remission (mean (SEM)) post pneumatic dilation was
      significantly (p=0.001) less for the discordant group (18.0 (3.6) months)
      compared with the concordant group (59.0 (4.8) months). CONCLUSIONS: (1) Poor
      oesophageal emptying is present in nearly 30% of achalasia patients reporting
      complete symptom relief post pneumatic dilation. (2) The majority (90%) of these
      patients will fail within one year of treatment. (3) Timed barium oesophagram is
      an important tool in the objective evaluation of achalasia patients post
      pneumatic dilation.

PMID- 12010877
TI  - Analysis of apoptotic and antiapoptotic signalling pathways induced by
      Helicobacter pylori.
AB  - BACKGROUND AND AIMS: Although it is reported that Helicobacter pylori induces
      apoptosis on gastric epithelial cells, the mechanism remains unknown.
      Antiapoptotic effects generated by H pylori have not yet been evaluated. METHODS:
      (1) H pylori strains (type 1 wild, TN2-DeltacagE, TN2-DeltavacA) were cocultured
      with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed
      by trypan blue exclusion and DNA laddering, respectively. (2) Activation of
      caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas
      associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were
      evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa
      B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H
      pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor
      Ikappabetaalpha were cocultured with H pylori, and cell viability and caspase
      activation were evaluated. NFkappaB regulated gene expression was also evaluated
      by ribonuclease protection assay. RESULTS: (1) Wild-type and DeltavacA mutant H
      pylori induced apoptosis more potently than the DeltacagE mutant. Inhibition of
      cell contact between H pylori and cancer cells and heat killing H pylori
      diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently
      by H pylori as well as by the agonist anti-Fas. Cytochrome c release from
      mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although
      protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates
      was not changed by H pylori, Bax was decreased from mitochondria free cytosol
      suggesting that Bax was translocated into mitochondria. (3) Cell death and the
      activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing
      super-repressor Ikappabetaalpha that inhibits NFkappaB activation. Antiapoptotic
      proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. CONCLUSION:
      cag PAI positive H pylori is capable of inducing apoptotic effects mainly through
      the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation
      were also observed.

PMID- 12010878
TI  - Risk factors for atrophic chronic gastritis in a European population: results of
      the Eurohepygast study.
AB  - BACKGROUND AND AIMS: The development of atrophic chronic gastritis (ACG) is
      multifactorial, involving environment as well as host responses to Helicobacter
      pylori infection. The aim of this study was to determine factors involved in ACG
      in a European dyspeptic population. METHODS: Data concerning sociodemographics,
      social behaviour, biological aspects, diet, and virulence factors of H pylori
      strains were collected in a cross sectional study from 19 European centres in 14
      countries. Dyspeptic H pylori positive patients with ACG or non-ACG (NACG) at
      histology were included. Anti-CagA antibodies were evaluated by two immunoblot
      tests and anti-VacA antibodies by one. Logistic regression models were
      constructed, and estimated odds ratios (ORs) and 95% confidence intervals (95%
      CI) were calculated from the coefficients. RESULTS: Of the 451 patients included
      in the study, 267 were analysed: 202 had NACG and 65 ACG. Mean age was 44.4 years
      and 63% were women. Risk factors for atrophy identified by multivariate analysis
      were: age over 60 years (OR 4.14, 95% CI 1.79-9.58), coffee consumption (OR 2.35,
      95% CI 1.07-5.16), sedative consumption (OR 2.17, 95% CI 1.04-4.52), and
      harbouring anti-CagA and anti-VacA antibodies simultaneously (OR 3.09, 95% CI
      1.26-7.56), while the odds were significantly reduced for those with an anxiety
      score of 6 or more (OR 0.45, 95% CI 0.21-0.99). CONCLUSION: The simultaneous
      presence of anti-CagA and anti-VacA antibodies enhanced the risk of ACG in
      European dyspeptic patients. Failure to discern diet and family history as risk
      factors for ACG may suggest that diet is homogeneous in Europe and that most of
      the risk factors for ACG identified so far are identical to risk factors for H.
      pylori infection.

PMID- 12010879
TI  - Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO
      cells.
AB  - BACKGROUND: Production of N-alpha-methyl-histamine (NAMH), a histamine H(3)
      receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected
      human gastric mucosa. NAMH was suggested to act directly on histamine H(2)
      receptors (H2Rs) in animals to stimulate acid secretion and to be a H2R agonist.
      As H2Rs and H3Rs play different roles in gastric acid secretion, it is very
      important to verify that NAMH is a H2R agonist. AIMS: To determine whether NAMH
      is a H2R agonist, as well as a H3R agonist. METHODS: We used a Chinese hamster
      ovary (CHO) cell line expressing human H2Rs (CHO-H2R) and control CHO cells.
      Expression of human H2Rs was confirmed by tiotidine binding. cAMP production in
      CHO-H2R and control cells in response to histamine or NAMH was measured. cAMP
      production in response to 10(-7) M NAMH was also measured in the presence or
      absence of the H2R antagonist famotidine and the H3R antagonist thioperamide.
      RESULTS: NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This
      production was inhibited by famotidine but not by thioperamide. Control CHO cells
      were unresponsive to either histamine or NAMH. In addition, the effect of NAMH,
      in terms of cAMP production in CHO-H2R cells, was more potent than that of
      histamine-that is, with a lower EC(50) concentration and higher maximal cAMP
      production. Both NAMH and histamine, but not R-alpha-methyl-histamine,
      effectively inhibited [(3)H] tiotidine binding to CHO-H2R cells. CONCLUSIONS:
      NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R
      agonist as well as a H3R agonist.

PMID- 12010880
TI  - Novel human and mouse genes encoding an acid phosphatase family member and its
      downregulation in W/W(V) mouse jejunum.
AB  - BACKGROUND AND AIMS: Interstitial cells of Cajal (ICC) are pacemakers and
      mediators of motor neurotransmission in gastrointestinal smooth muscles. ICC
      require cellular signalling via Kit, a receptor tyrosine kinase, for development
      and maintenance of phenotype. Much of the evidence demonstrating the functions of
      ICC comes from studies of W/W(V) mice, which have reduced Kit function and
      reductions in specific populations of ICC. The aim of the present study was to
      differentially examine gene expression in the small intestines of wild-type and
      W/W(V) mutant mice. METHODS AND RESULTS: RNA from the jejunums of wild-type and
      W/W(V) mutants was analysed using a differential gene display method. Eighteen
      queries were identified as novel genes that were differentially displayed in wild
      type and W/W(V) mice. One candidate gene, encoding a novel acid phosphatase-like
      protein, was significantly suppressed in fed and starved W/W(V) mice. The full
      length clone of the murine gene and its human counterpart were designated acid
      phosphatase-like protein 1 (ACPL1). Human ACPL1 cDNA encodes a protein of 428
      amino acids with homology to human prostatic acid phosphatase protein. This gene
      is located at 1q21. ACPL1 was abundantly expressed in the human small intestine
      and colon. Gene products were found to be cytoplasmic in transfected COS-7 cells.
      Reverse transcription-polymerase chain reaction analysis revealed expression of
      ACPL1 mRNA within single isolated ICCs. CONCLUSIONS: Gene analysis showed that
      ACPL1 was differentially expressed in the small intestines of normal and W/W(V)
      mice. ICC within the small intestine expressed mRNA for ACPL1. Specific
      downregulation of ACPL1 in the jejunums of W/W(V) mice and high expression in
      human intestinal tissue suggest that the ACPL1 gene could be associated with ICC
      function in mice and humans.

PMID- 12010881
TI  - Distribution of the long leptin receptor isoform in brush border, basolateral
      membrane, and cytoplasm of enterocytes.
AB  - BACKGROUND AND AIM: Leptin, a hormone mainly produced by fat cells, acts
      primarily on the hypothalamus regulating energy expenditure and food intake.
      Leptin receptors are expressed in several tissues and the possible physiological
      role of leptin is being extensively investigated, with the result that important
      peripheral actions of the hormone in the organism are being discovered. Recent
      studies have demonstrated leptin and leptin receptor expression in gastric
      epithelial cells. In the present study, we report the presence of the long leptin
      receptor isoform (OB-Rb) in human, rat, and mouse small intestine, supporting the
      hypothesis of leptin as a hormone involved in gastrointestinal function. METHODS:
      The presence of the leptin receptor was determined by immunocytochemical methods
      using antibodies against the peptide corresponding to the carboxy terminus of the
      long isoform of the leptin receptor. Human duodenal biopsies from normal
      individuals undergoing gastrointestinal endoscopy, and intestinal fragments of
      Wistar rats and Swiss mice were processed for the study. RESULTS:
      Immunoreactivity for the long leptin receptor isoform was observed in the three
      studied species. Staining was located throughout the cytoplasm of the
      enterocytes, of both villi and crypts, and in the basolateral plasma membrane.
      Immunolabelling for OB-Rb protein was also found in the brush border of human
      enterocytes of formol and paraformaldehyde fixed samples. CONCLUSION: This report
      demonstrates the presence of the long leptin receptor isoform in the absorptive
      cells of rat, mouse, and human small intestine, suggesting that leptin could have
      a physiological role in the regulation of nutrient absorption.

PMID- 12010882
TI  - Lactobacillus acidophilus (strain LB) from the resident adult human
      gastrointestinal microflora exerts activity against brush border damage promoted
      by a diarrhoeagenic Escherichia coli in human enterocyte-like cells.
AB  - BACKGROUND AND AIMS: The normal gastrointestinal microflora exerts a barrier
      effect against enteropathogens. The aim of this study was to examine whether
      lactobacilli, a minor genus of the resident gut microflora, exerts a protective
      effect against the cellular injuries promoted by the diarrhoeagenic Afa/Dr
      diffusely adhering Escherichia coli (Afa/Dr DAEC) C1845 strain in human
      intestinal cells. METHODS: Cultured human intestinal fully differentiated
      enterocyte-like Caco-2/TC7 cells were used. Antibacterial activity was examined
      by measuring the viability of the adhering C1845 bacteria. The distribution of
      brush border associated cytoskeleton and functional proteins was examined by
      immunofluorescence labelling coupled to confocal laser scanning microscopy
      analysis. RESULTS: The activity of Lactobacillus acidophilus strain LB isolated
      from the resident human gastrointestinal microflora was examined. A dose
      dependent decrease in viability of C1845 bacteria was observed after both direct
      contact in vitro between the spent culture supernatant (LB-SCS) and the bacteria,
      and when the bacteria were adherent on Caco-2/TC7 cells. Protection against the
      C1845 induced alterations in expression of F-actin, sucrase-isomaltase,
      dipeptidylpeptidase IV, alkaline phosphatase, and fructose transporter
      alterations was observed when the cells were exposed to LB-SCS. CONCLUSION: L
      acidophilus strain isolated from the resident adult human gastrointestinal
      microflora, together with its antimicrobial activity, exerts a protective effect
      against the brush border lesions promoted by the diarrhoeagenic Afa/Dr DAEC
      strain C1845.

PMID- 12010883
TI  - Interleukin 18 is a primary mediator of the inflammation associated with dextran
      sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal
      damage.
AB  - BACKGROUND AND AIMS: Persistent inflammation observed in inflammatory bowel
      disease may be the consequence of an increased or aberrant immune response to
      normal gut constituents or an overall immune dysregulation and imbalance.
      Cytokines play an important role in immune regulation and interleukin 18 (IL-18)
      is one such cytokine that has emerged as being instrumental in driving CD4+ T
      cell responses towards a Th1-type. IL-18 can also directly mediate inflammation,
      moderate interleukin 1 activity, and can act on cell types other than T cells. It
      has been reported recently that IL-18 mRNA and protein are upregulated in gut
      tissue from IBD patients. The aim of this study was to understand more about the
      role of IL-18 in contributing to the pathology of IBD and to assess whether
      blocking IL-18 activity may be of therapeutic benefit as a treatment regimen for
      IBD. METHODS: Mice with dextran sulphate sodium (DSS) induced colitis were
      treated with recombinant IL-18 binding protein (IL-18bp.Fc), a soluble protein
      that blocks IL-18 bioactivity. Histopathological analysis was performed and RNA
      from the large intestine was analysed using the RNase protection assay and gene
      arrays. RESULTS: IL-18 RNA levels increased very early in the colon during DSS
      colitis. Treatment of mice with IL-18bp.Fc inhibited IBD associated weight loss
      and significantly inhibited the intestinal inflammation induced by DSS. IL
      18bp.Fc treatment also attenuated mRNA upregulation of multiple proinflammatory
      cytokine genes, chemokine genes, and matrix metalloprotease genes in the large
      intestine that are commonly elevated during IBD. CONCLUSIONS: IL-18bp treatment
      attenuated inflammation during DSS induced colitis in mice. Neutralising IL-18
      activity may therefore be of benefit for ameliorating the inflammation associated
      with human intestinal diseases.

PMID- 12010884
TI  - Impairment of epithelial transport but not of barrier function in idiopathic
      pouchitis after ulcerative colitis.
AB  - BACKGROUND AND AIMS: Little is known of the permeability of ileoanal pouches.
      Hence the aim of the present study was to determine changes in permeability and
      mucosal function after ileo-pouchanal anastomosis (IPAA) in patients with
      ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from 43 patients
      (male:female ratio 28:15; mean age 35.2 (12.5) years) prior to colectomy (ileum
      prior to pouch), prior to closure of ileostomy (deviation), and after closure of
      ileostomy (intact pouch) in the case of pouchitis, and from 14 healthy controls.
      Tissues were mounted in a miniaturised Ussing chamber. Epithelial and
      subepithelial resistance was determined by transmural impedance analysis. Active
      Na(+)-glucose cotransport was measured as change in short circuit current after
      stepwise addition of glucose, and active Cl(-) secretion was measured after
      stimulation with theophylline and prostaglandin E(2). RESULTS: Neither epithelial
      resistance nor mannitol fluxes were significantly altered compared with intact
      controls, indicating no barrier defect in pouchitis. Subepithelial resistances of
      intact pouches and pouchitis were increased compared with deviation (18.2 (1.6)
      and 24.3 (1.5) v. 13.6 (1.0) Omegaxcm(2)) consistent with an adaptive thickening
      of the subepithelial layer. In contrast, active Cl(-) secretion of pouchitis
      tissues was reduced versus intact pouch and controls (1.4 (0.3) v. 4.3 (0.7) and
      4.6 (0.7) micromol/h/cm(2)), and Na(+)-glucose cotransport of pouchitis was
      reduced compared with intact pouch and controls (1.8 (0.5) v. 4.2 (0.8) and 8.8
      (1.3) micromol/h/cm(2)). CONCLUSIONS: Ileal mucosa in pouchitis and terminal
      ileum prior to IPAA exhibit impaired secretory and absorptive transport functions
      whereas the epithelial barrier function remains unchanged. This differs from
      findings in ulcerative colitis. Thus the hypothesis that pouchitis represents a
      remanifestation of ulcerative colitis has to be questioned.

PMID- 12010885
TI  - Gastrin-cholecystokinin(B) receptor expression in AGS cells is associated with
      direct inhibition and indirect stimulation of cell proliferation via paracrine
      activation of the epidermal growth factor receptor.
AB  - BACKGROUND: Activation of the gastrin-cholecystokinin(B) (CCK(B)) receptor
      stimulates cell proliferation and increases production of ligands for the
      epidermal growth factor receptor (EGF-R). AIMS: To determine the role of gastrin
      CCK(B) activation in stimulation of cell proliferation via paracrine activation
      of EGF-R. METHODS: AGS cells were transfected with the gastrin-CCK(B) receptor
      (AGS-G(R) cells) or with green fluorescent protein (AGS-GFP cells). Proliferation
      was determined by [(3)H] thymidine incorporation, flow cytometry, and cell
      counting. RESULTS: Gastrin inhibited proliferation of AGS-G(R) cells by delaying
      entry into S phase. However, when AGS-G(R) cells were cocultured with AGS-GFP
      cells, gastrin stimulated proliferation of the latter. Immunoneutralisation and
      pharmacological studies using metalloproteinase and kinase inhibitors indicated
      that the proliferative response was mediated by paracrine stimulation of EGF-R
      and activation of the mitogen activated protein kinase pathway through release of
      heparin binding EGF. CONCLUSIONS: Gastrin can directly inhibit, and indirectly
      stimulate, proliferation of gastric AGS cells.

PMID- 12010886
TI  - The spectrum of p53 mutations in colorectal adenomas differs from that in
      colorectal carcinomas.
AB  - BACKGROUND: p53 mutations are frequently observed in colorectal carcinomas but
      they have also been found in colorectal adenomas, although considerably less
      frequently. AIMS: To explore p53 mutations in benign tumours, we have screened 70
      colorectal adenomas for allelic loss at, and point mutations in, TP53 by analysis
      of selected microdissected cell populations. RESULTS: Sixteen (22.8%) adenomas
      were found to have allelic loss, of which 11 (15.7%) had p53 mutations. In
      adenomas with mild, moderate, or severe dysplasia, mutation or allelic loss
      occurred in 4.8%, 16.7%, and 52.6%, respectively (p<0.001). Seven different
      mutations were found, all missense changes or inframe deletions: one (Thr150Arg)
      has not been found before while three (Gln144His, Gly245Arg, and Glu285Gln) have
      not been described previously in colorectal tumours. The other three mutations
      (Arg175Gly, DeltaPro190, and Gly245Ser) have been found in colorectal carcinomas,
      the last commonly. Adenomas harboured a spectrum of p53 mutations which was
      significantly different from cancers as regards the position in the gene and a
      higher frequency of G-->C/C-->G changes. CONCLUSIONS: Combining our data on
      adenomas with data already published and in comparison with the spectrum of
      mutations in colorectal carcinomas, it is suggested that some p53 mutations have
      a weaker effect than others and are therefore more likely to be found in adenomas
      which have not progressed to carcinomas.

PMID- 12010887
TI  - Effect of faecal occult blood screening on mortality from colorectal cancer:
      results from a randomised controlled trial.
AB  - BACKGROUND: Three large randomised trials have shown that screening for
      colorectal cancer using faecal occult blood (FOB) tests can reduce the mortality
      from this disease. Two national pilot studies have recently been launched in the
      UK to investigate the feasibility of population screening for colorectal cancer
      in the National Health Service. The largest of the randomised trials was
      conducted in Nottingham and randomised 152 850 individuals between the ages of 45
      and 74 years to receive biennial Haemoccult (FOB) test kit (intervention group)
      or to a control group. AIMS: We have compared the mortality in the intervention
      group compared with the control group. METHODS: The 152 850 randomised
      individuals were followed up through local health records and central flagging
      (Office for National Statistics) over a median follow up period of 11 years.
      RESULTS: At a median follow up of 11 years there was a 13% reduction in
      colorectal cancer mortality (95% confidence interval 3-22%) in the intervention
      group despite an uptake at first invitation of only approximately 50%. The
      mortality reduction for those accepting screening was 27%. The reduction in
      mortality was independent of sex and site of tumour. There was no significant
      difference in mortality from causes other than colorectal cancer between the
      intervention and control groups. CONCLUSIONS: Although the reduction in
      colorectal cancer mortality was sustained, further follow up of this population
      is required to determine whether a significant reduction in the incidence of
      colorectal cancer will be achieved.

PMID- 12010888
TI  - Genetic and clinical characterisation of familial adenomatous polyposis: a
      population based study.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is a rare autosomal dominantly
      inherited disease predisposing to colon cancer and caused by germline mutations
      in the APC (adenomatous polyposis coli) gene. AIMS: We conducted a population
      based study to evaluate the prevalence and clinical implications of APC mutations
      among Finnish FAP kindreds. A possible founder effect in parallel with previous
      observations in hereditary non-polyposis colon cancer (HNPCC) was addressed.
      PATIENTS: Affected individuals from 65 kindreds were included. METHODS: The APC
      gene was screened for mutations using the protein truncation test and
      heteroduplex analysis. Haplotype analysis was performed with four flanking
      microsatellite markers. Families that failed to show any mutations were
      scrutinised with Southern blot hybridisation and allelic expression analysis.
      RESULTS: Thirty eight different germline mutations in APC were identified in 47
      kindreds (72%). The majority of these mutations were novel and unique to each
      family. Although sharing the classical polyposis phenotype, families without
      detectable APC mutations differed from mutation positive families in the
      following respects: firstly, mean age at polyposis diagnosis was higher (38.6
      years (48 individuals) v 30.0 years (140 individuals); p=0.001); and secondly,
      the proportion of kindreds lacking extracolonic disease was higher (6/18 v. 5/47;
      p=0.04). CONCLUSIONS: Our results may pave the way for predictive testing in
      mutation positive families and should stimulate further molecular studies in
      mutation negative families. No founder effect was observed, which is in contrast
      with HNPCC in the same population.

PMID- 12010889
TI  - Polymorphisms of the human UDP-glucuronosyltransferase (UGT) 1A7 gene in
      colorectal cancer.
AB  - BACKGROUND: Genetic polymorphisms in the human UDP-glucuronosyltransferase-1A7
      (UGT1A7) gene are detected and significantly correlated with sporadic colorectal
      carcinoma. UGT1A7, which has recently been demonstrated to glucuronidate
      environmental carcinogens, is now implicated as a cancer risk gene. A silent
      mutation at codon 11 and missense mutations at codons 129, 131, and 208 lead to
      the description of three polymorphic alleles designated UGT1A7*2, UGT1A7*3, and
      UGT1A7*4. METHODS: UGT1A7 polymorphisms were analysed by polymerase chain
      reaction amplification and sequencing, as well as temperature gradient gel
      electrophoresis in 210 healthy blood donors and 78 subjects with colorectal
      cancer. RESULTS: Homozygous wild-type UGT1A7 alleles were present in 20% of
      normal controls but were only detected in 9% of patients with colorectal
      carcinoma (odds ratio (OR) 0.39 (95% confidence interval (CI) 0.17-0.92);
      p=0.03). Analysis of individual polymorphic alleles identified a highly
      significant association between the presence of UGT1A7*3 alleles and colorectal
      cancer (OR 2.75 (95% CI 1.6 - 4.71); p<0.001). Recombinant expression of UGT1A7
      polymorphic cDNA in eukaryotic cell culture showed reduced carcinogen
      glucuronidation activity in comparison with wild-type UGT1A7. UGT1A7 may
      therefore represent a modifier gene in colorectal carcinogenesis. CONCLUSION: We
      have identified a potential novel risk factor in sporadic colorectal cancer which
      may contribute to the identification of risk groups and to the elucidation of
      factors involved in colon carcinogenesis.

PMID- 12010890
TI  - A randomised, double blind, placebo controlled study of celecoxib, a selective
      cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous
      polyposis.
AB  - BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti
      inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial
      adenomatous polyposis (FAP). Their role in the duodenum of these patients is less
      certain. The disease modifying activity of specific COX-2 inhibitors has not been
      explored in humans. PATIENTS AND METHODS: This was a randomised, double blind,
      placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice
      daily (n=32)) versus placebo (n=17), given orally twice daily for six months to
      patients with FAP. Efficacy was assessed qualitatively by blinded review of
      shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry
      and at six months and quantitatively by measurement of the percentage change in
      duodenal area covered by discrete and plaque-like adenomas from photographs of
      high and low density polyposis. RESULTS: Shuffled and blinded video review showed
      a statistically significant effect of 400 mg twice daily celecoxib compared with
      placebo treatment (p=0.033) with all five independent observers scoring a
      beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a
      14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436).
      However, patients with clinically significant disease at baseline (greater than
      5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400
      mg twice daily compared with 8% on placebo (p=0.049). CONCLUSIONS: A panel of
      five endoscopists found a significant reduction in duodenal polyposis after six
      months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help
      this otherwise untreatable condition.

PMID- 12010891
TI  - Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous
      tumours of the pancreas is associated with invasive ductal adenocarcinoma.
AB  - BACKGROUND AND AIMS: Intraductal papillary mucinous tumours (IPMT) of the
      pancreas constitute a unique pathological entity with an overall incidence of
      associated invasive malignancy of 20%. The malignant potential of an individual
      IPMT cannot be accurately predicted. Preoperative estimation of the risk of
      associated invasive malignancy with IPMT would be of significant clinical
      benefit. As aberrations in cell cycle regulatory genes are associated with the
      progression of precursor pancreatic ductal lesions to invasive adenocarcinoma, we
      examined expression of key cell cycle regulatory genes in the cyclin
      D1/retinoblastoma pathway and the transforming growth factor beta/Smad4
      signalling pathway in a cohort of patients with surgically resected IPMT.
      METHODS: Sections of formalin fixed paraffin embedded pancreatic tissue from a
      cohort of 18 patients with IPMT were examined using immunohistochemistry for
      protein expression of cell cycle regulatory genes p16(INK4A), p21(CIP1),
      p27(KIP1), cyclin D1, pRb, and p53, as well as the cell signalling molecule
      Smad4. A comparison of expression levels was made between adenoma/borderline IPMT
      (10 patients) and intraductal papillary mucinous carcinoma (IPMC) (eight
      patients, four of whom harboured invasive carcinoma). Statistical analysis was
      performed using the chi(2) and Fisher's exact tests. RESULTS: Aberrant expression
      of the proteins examined increased in frequency from adenoma/borderline IPMT to
      IPMC. Specifically, there was a significantly greater incidence of loss of
      p16(INK4A) expression in IPMC: 8/8 lesions (100%) compared with 1/10 (10%)
      adenoma/borderline IPMT (p<0.001). Similarly, loss of Smad4 expression was
      associated with IPMC: 3/8 (38%) versus adenoma/borderline IPMT 0/10 (p<0.03).
      Loss of Smad4 expression within the IPMT was the best marker for the presence of
      invasive carcinoma (p<0.001). CONCLUSIONS: These data indicate that loss of
      p16(INK4A) and Smad4 expression occur more frequently in IPMC alone, or with
      associated invasive carcinoma, compared with adenoma/borderline IPMT. Aberrant
      protein expression of these cell cycle regulatory genes in IPMT and pancreatic
      intraepithelial neoplasia in the current model of pancreatic cancer progression
      suggest similarities in their development and may also represent the subsequent
      risk of invasive carcinoma.

PMID- 12010892
TI  - Selective plasma filtration for treatment of fulminant hepatic failure induced by
      D-galactosamine in a pig model.
AB  - BACKGROUND: Plasma exchange may be useful for treating patients with fulminant
      hepatic failure but during the procedure growth factors that are important for
      hepatic regeneration are discarded. Addition of a selective plasma filter to the
      plasmapheresis circuit could eliminate protein bound toxic substances and retain
      growth factors for hepatic regeneration. This process is called selective plasma
      filtration. AIMS: To determine if selective plasma filtration could be a useful
      treatment modality for fulminant hepatic failure. METHODS: The system was tested
      in five groups of pigs with fulminant hepatic failure induced by galactosamine:
      group I, diseased control group (n=5); group II, sham control, (n=6); group III,
      plasma exchange (n=6); group IV, treatment with AC-1770 selective plasma filter
      (n=7); and group V, treatment with AC-1730 selective plasma filter which had a
      smaller pore size than AC-1770 (n=7). Fresh pig plasma was given to replace
      filtered plasma in pigs of groups III, IV, and V. Treatment was initiated 48
      hours after administration of 0.75 g/kg galactosamine. The efficacy of selective
      plasma filtration was assessed by survival rate and improvement in
      haematological, biochemical, and immunohistological parameters. RESULTS: Pigs
      treated with AC-1770 or AC-1730 selective plasma filters survived longer than the
      other groups (group I: 55 (10) hours; group II: 68 (7) hours; group III: 91 (10)
      hours; group IV: 269 (156) hours; group V: 950 (555) hours). One pig in group IV
      survived for 50 days; one pig in group V survived for 77 days and another pig in
      group V is still alive (>150 days). After treatment, plasma levels of aspartate
      aminotransferase, bilirubin, bile acid, ammonia, lactate dehydrogenase, and alpha
      glutathione-S-transferase decreased. Substantial amounts of tumour necrosis
      factor alpha (TNF-alpha) and endotoxin were found in the filtrate. The selective
      plasma filtration groups retained significantly higher amounts of hepatocyte
      growth factor than plasma exchange alone. Similar TNF-alpha clearance was
      observed in the selective plasma filtration groups and the plasma exchange group.
      On day 4, significant improvement in liver function, as measured by the
      indocyanine green clearance test, was observed in groups IV and V but not in the
      other groups. A higher regeneration index of hepatocytes was also observed in the
      groups treated with AC-1770 and AC-1730 selective plasma filters. CONCLUSION:
      Selective plasma filtration improved survival time and expedited liver
      regeneration in pigs with fulminant hepatic failure.

PMID- 12010893
TI  - Focal nodular hyperplasia of the liver in men: is presentation the same in men
      and women?
AB  - BACKGROUND: Focal nodular hyperplasia (FNH) of the liver is a benign hepatic
      lesion relatively common in women. No studies specifically designed to describe
      the presentation and imaging findings in males have been published. AIMS: The
      aims of this study were: (a) to describe the clinical and imaging findings in 18
      men with FNH, and (b) to compare these data with those observed in 216 women with
      FNH observed during the same nine year period. PATIENTS AND METHODS: According to
      a final diagnosis of FNH assessed either by pathological examination or by
      magnetic resonance (MR), the medical charts of 18 men with FNH observed at our
      institution were reviewed. In order to compare clinical and MR presentations, the
      files of 216 women with a total of 291 FNH lesions, investigated during the same
      nine year period, were reviewed. RESULTS: Eighteen FNH lesions, with a mean
      diameter of 37.5 mm, were demonstrated in the 18 male patients. A total of 291
      lesions with a mean diameter of 63.4 mm were comparatively demonstrated in 216
      female patients. Mean age at diagnosis was significantly higher in men (p<0.01)
      and mean FNH size was significantly smaller in men (p<0.001). Surgery was more
      frequently performed in men (72.2%) than in women (16.7%) (p<0.001). CONCLUSIONS:
      Our data indicate that FNH is rare in men and that the lesions are smaller and
      more often atypical than those in women.

PMID- 12010894
TI  - Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child
      Pugh staging systems in a cohort of 257 patients in Toronto.
AB  - BACKGROUND: A new staging system for hepatocellular carcinoma (HCC) has recently
      been reported from Italy (CLIP classification). It combines Child-Pugh staging
      with tumour criteria: tumour morphology, portal invasion, and alpha fetoprotein
      levels. AIMS: To validate the use of the CLIP staging in a cohort of HCC patients
      and compare it with Okuda staging. PATIENTS AND METHODS: A retrospective analysis
      of patients with HCC diagnosed in the Toronto General Hospital between October
      1994 and December 1998. RESULTS: A total of 313 patients were identified; 19
      patient with insufficient data and 37 transplant patients were excluded. Hence
      257 patients in whom complete data for clinical staging were available were
      included in the study. The median survival of the cohort was 22.8 months. The
      CLIP stage 0 group (23.1% of the cohort) and the Okuda stage 1 group (50.7% of
      the cohort) had a five year survival rate of 67% and 35%, respectively (p<0.02).
      The CLIP stage 0 criteria more accurately defined patients with a good prognosis.
      The Okuda classification failed to identify two thirds of the 37 patients with a
      poor prognosis, who were identified by the CLIP criteria. Patients with a CLIP
      score > or =4 shared a very poor prognosis (median survival 1-3 months). Further
      classification above stage 4 was unnecessary. SUMMARY: The CLIP classification
      for HCC is easy to implement and more accurate than the Okuda classification. Our
      cohort was different from the CLIP cohort (more hepatitis B) but the results were
      still consistent.

PMID- 12010895
TI  - A god for guts.

PMID- 12010896
TI  - Creutzfeldt-Jakob disease: implications for gastroenterology.
AB  - The current clinical views regarding variant Creutzfeldt-Jakob disease, and in
      particular transmission via endoscopy, of those representing both
      gastroenterology and the Spongiform Encephalopathy Advisory Committee are
      presented in an attempt to guide clinicians as to "best practice" given the
      current state of our knowledge.

PMID- 12010897
TI  - Transcriptional regulation of hepatic stellate cell activation.
AB  - The hepatic stellate cell (HSC) is now well established as the key cellular
      element involved in the development of hepatic fibrosis and because of this there
      is considerable interest in establishing the molecular events that trigger and
      perpetuate HSC activation. HSC activation at the level of gene transcription
      requires the coordinated activity of several key transcriptional regulators of
      the HSC genome. The considerable advances that have been made in the past five
      years into the mechanisms by which specific families of transcription factors
      regulate the profibrogenic characteristics of the activated HSC are reviewed.

PMID- 12010898
TI  - Regulation of gastric function by gastrin releasing peptide.

PMID- 12010899
TI  - Hypomagnesaemia due to malabsorption is not always responsive to oral magnesium
      oxide supplementation alone.

PMID- 12010900
TI  - Osteoporosis is not a specific complication of primary biliary cirrhosis (PBC).

PMID- 12010901
TI  - Expression of isoforms of nitric oxide synthase in collagenous colitis.

PMID- 12010903
TI  - Calcineurin signaling in human cardiac hypertrophy.

PMID- 12010904
TI  - Contemporary medical options for treating patients with heart failure.

PMID- 12010905
TI  - Physical activity and coronary event incidence in Northern Ireland and France:
      the Prospective Epidemiological Study of Myocardial Infarction (PRIME).
AB  - BACKGROUND: The influence of physical activity on the incidence of angina
      pectoris and hard coronary events (myocardial infarction and coronary deaths) was
      examined in Northern Ireland and France at contrasting risk for coronary heart
      disease (CHD) and with different physical activity patterns. METHODS AND RESULTS:
      Participants of the Prospective Epidemiological Study of Myocardial Infarction
      (PRIME) (n=9758; age, 50 to 59 years), free of CHD at baseline, were followed up
      for 5 years: 167 hard CHD and 154 angina events were recorded. Net energy
      expenditure (EE) as the result of physical activity was assessed by means of the
      MONICA Optional Study of Physical Activity Questionnaire (MOSPA-Q). Leisure-time
      physical activity EE was calculated; subjects were also categorized as to whether
      they performed high-intensity leisure-time activities or walked or cycled to
      work. After multivariate adjustment, leisure-time physical activity EE was
      associated with a lower risk of hard CHD events (P<0.04), whereas walking or
      cycling to work was not independently related to hard CHD events. No interaction
      by country was found. The beneficial effect of leisure-time physical activity was
      also present among subjects who did not report high-intensity activities
      (P<0.04), with similar results in France and Northern Ireland. In contrast, an
      increasing level of leisure-time physical activity was associated with a higher
      risk of angina in both countries. CONCLUSIONS: These data indicate a beneficial
      effect of leisure-time physical activity EE on hard CHD incidence in middle-aged
      men, which could partly explain the unfavorable rate of CHD in Northern Ireland.
      The higher level of leisure-time activities in France could, in part, explain its
      lower rate of CHD.

PMID- 12010906
TI  - Outcomes of patients with chronic renal insufficiency in the bypass angioplasty
      revascularization investigation.
AB  - BACKGROUND: Although severe chronic kidney disease (CKD) is an independent
      predictor of mortality among patients with coronary artery disease, the impact of
      mild CKD on morbidity and mortality has not been fully defined. METHODS AND
      RESULTS: Morbidity and mortality for the 3608 patients with multivessel coronary
      artery disease enrolled in the Bypass Angioplasty Revascularization Investigation
      randomized trial and registry were compared on the basis of the presence and
      absence of CKD, defined as a preprocedure serum creatinine level of >1.5 mg/dL.
      Seventy-six patients had CKD. Patients with renal insufficiency were older and
      more likely to have a history of diabetes, hypertension, and other comorbidities.
      Among patients undergoing PTCA, patients with CKD had a greater frequency of in
      hospital death and cardiogenic shock (P<0.05 and 0.01, respectively). There was a
      trend toward a larger proportion of patients with CKD experiencing angina at 5
      years (P=0.079). Patients with CKD had more cardiac admissions (P=0.003 and
      <0.0001 for patients undergoing PTCA and CABG, respectively) and a shorter time
      to subsequent CABG after initial revascularization than patients without CKD
      (P=0.01). CKD was associated with a higher risk of death at 7 years, both of all
      causes (relative risk 2.2, P<0.001) and of cardiac causes (relative risk 2.8,
      P<0.001). CONCLUSIONS: CKD is associated with an increased risk of recurrent
      hospitalization, subsequent CABG, and mortality. This increased risk of death is
      independent of and additive to the risk associated with diabetes.

PMID- 12010907
TI  - Incidence and prognostic importance of acute renal failure after percutaneous
      coronary intervention.
AB  - BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in
      the modern era, the incidence and prognostic implications of acute renal failure
      (ARF) are unknown. METHODS AND RESULTS: With a retrospective analysis of the Mayo
      Clinic PCI registry, we determined the incidence of, risk factors for, and
      prognostic implications of ARF (defined as an increase in serum creatinine [Cr]
      >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced
      ARF. Among patients with baseline Cr <2.0, the risk of ARF was higher among
      diabetic than nondiabetic patients, whereas among those with a baseline Cr >2.0,
      all had a significant risk of ARF. In multivariate analysis, ARF was associated
      with baseline serum Cr, acute myocardial infarction, shock, and volume of
      contrast medium administered. Twenty-two percent of patients with ARF died during
      the index hospitalization compared with only 1.4% of patients without ARF
      (P<0.0001). After adjustment, ARF remained strongly associated with death. Among
      hospital survivors with ARF, 1- and 5-year estimated mortality rates were 12.1%
      and 44.6%, respectively, much greater than the 3.7% and 14.5% mortality rates in
      patients without ARF (P<0.0001). CONCLUSIONS: The overall incidence of ARF after
      PCI is low. Diabetic patients with baseline Cr values <2.0 mg/dL are at higher
      risk than nondiabetic patients, whereas all patients with a serum Cr >2.0 are at
      high risk for ARF. ARF was highly correlated with death during the index
      hospitalization and after dismissal.

PMID- 12010908
TI  - Calcineurin in human heart hypertrophy.
AB  - BACKGROUND: In animal models, increased signaling through the calcineurin pathway
      has been shown to be sufficient for the development of cardiac hypertrophy.
      Calcineurin activity has been reported to be elevated in the myocardium of
      patients with congestive heart failure. In contrast, few data are available about
      calcineurin activity in patients with pressure overload or cardiomyopathic
      hypertrophy who are not in cardiac failure. METHODS AND RESULTS: We investigated
      calcineurin activity and protein expression in 2 different forms of cardiac
      hypertrophy: hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis
      (AS). We found that the C-terminus of calcineurin A protein containing the
      autoinhibitory domain was less abundant in myocardial hypertrophy than in normal
      heart, which suggests the possibility of proteolysis. No new splice variants
      could be detected by reverse-transcription polymerase chain reaction. This
      resulted in a significant elevation of calcineurin enzymatic activity in HOCM and
      AS compared with 6 normal hearts. Increased calcineurin phosphatase activity
      caused increased migration of NF-AT2 (nuclear factor of activated T cells 2) in
      SDS-PAGE compatible with pronounced NF-AT dephosphorylation in hypertrophied
      myocardial tissue. CONCLUSIONS: Hypertrophy in HOCM and AS without heart failure
      is characterized by a significant increase in calcineurin activity. This might
      occur by (partial) proteolysis of the calcineurin A C-terminus containing the
      autoinhibitory domain. Increased calcineurin activity has functional relevance,
      as shown by altered NF-AT phosphorylation state. Although hypertrophy in AS and
      HOCM may be initiated by different upstream triggers (internal versus external
      fiber overload), in both cases, there is activation of calcineurin, which
      suggests an involvement of this pathway in the pathogenesis of human cardiac
      hypertrophy.

PMID- 12010909
TI  - Effects of interrupting precordial compressions on the calculated probability of
      defibrillation success during out-of-hospital cardiac arrest.
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) creates artifacts on the ECG and,
      with automated defibrillators, a pause in CPR is mandatory during rhythm
      analysis. The rate of return of spontaneous circulation (ROSC) is reduced with
      increased duration of this hands-off interval in rats. We analyzed whether
      similar hands-off intervals in humans with ventricular fibrillation causes
      changes in the ECG predicting a lower probability of ROSC. METHODS AND RESULTS:
      The probability of ROSC after a shock was continually determined from ECG signal
      characteristics for up to 20 seconds of 634 such hands-off intervals in patients
      with ventricular fibrillation. In hands-off intervals with an initially high (40%
      to 100%) or median (25% to 40%) probability for ROSC, the probability was
      gradually reduced with time to a median of 8% to 11% after 20 seconds (P<0.001).
      In episodes with a low initial probability (0% to 25%; median, 5%), there was no
      further reduction with time. CONCLUSIONS: The interval between discontinuation of
      chest compressions and delivery of a shock should be kept as short as possible.

PMID- 12010910
TI  - Pooling in chronic orthostatic intolerance: arterial vasoconstrictive but not
      venous compliance defects.
AB  - BACKGROUND: Orthostatic intolerance is characterized by postural tachycardia
      syndrome (POTS) with exaggerated tachycardia, orthostatic symptoms, and "pooling"
      (which comprises acrocyanosis and dependent edema when upright). My colleagues
      and I tested the hypothesis that pooling results from increased venous compliance
      in POTS patients. METHODS AND RESULTS: Fifteen patients aged 13 to 19 years were
      compared with 11 healthy, age-matched controls. The POTS group was divided into
      patients with high venous pressure (P(v)>20 mm Hg) and normal P(v) on the basis
      of resting supine P(v) obtained in previous work. Subjects were studied using
      strain gauge plethysmography to measure blood flow, P(v), and the venous
      compliance volume-pressure relation while supine and during incremental head-up
      tilt testing at -10 degrees, 0 degrees, 20 degrees, and 35 degrees. Volume
      pressure relations of controls and POTS patients with normal P(v) and high P(v)
      were not different and were unchanged by orthostasis. Supine leg peripheral
      resistance was greater than control resistance in patients with high P(v) (54+/-9
      versus 30+/-6 mm Hg x mL(-1) x 100 mL(-1) x min(-1)) and less than control
      resistance in patients with normal P(v) (17+/-2 mm Hg x mL(-1) x 100 mL(-1) x
      min(-1)). On upright tilt, resistance decreased in high P(v) to approximate
      resistance in normal P(v). Resistance in controls increased throughout tilt. Leg
      P(v) increased in patients with normal P(v) and in controls but remained
      unchanged in the high P(v) group. CONCLUSIONS: The findings suggest that pooling
      in POTS is due to blunted arterial vasoconstriction, which produces passive
      redistribution of blood within peripheral venous capacitance beds. Venous
      compliance in POTS is similar to that in control subjects.

PMID- 12010911
TI  - Inhibition of tissue factor gene induction and activity using a hairpin ribozyme.
AB  - BACKGROUND: Tissue factor (TF) is a membrane-bound glycoprotein that initiates
      the clotting cascade. Inhibition of the TF pathway has been shown to prevent
      thrombosis and restenosis after arterial injury in a variety of animal models.
      METHODS AND RESULTS: We describe a novel approach to inhibiting the expression of
      the TF protein that involves the targeted destruction of cellular TF mRNA with
      the use of a tetraloop hairpin ribozyme. After construction of the ribozyme and
      determination of its optimal length and kinetic parameters, a ribozyme expression
      vector that used the retroviral vector pMV12 was constructed. The ability of this
      expression vector to generate anti-TF ribozyme was further augmented by
      positioning of the anti-TF ribozyme downstream of a rat tRNA val (RNA polymerase
      II) promoter. The resultant construct containing the anti-TF ribozyme was then
      used to transfect vascular smooth muscle cells and generate a variety of clonal
      cell lines. Northern blot analyses performed on 3 transfected and 3 untransfected
      clones demonstrated markedly reduced TF mRNA levels in the transfected clones
      both during quiescence and after serum stimulation. Cell lysates analyzed for
      total TF activity by monitoring factor Xa generation similarly demonstrated a
      statistically significant and concordant reduction in TF activity in smooth
      muscle cells transfected with the ribozyme expression vector compared with both
      untransfected clones and clones transfected with the empty vector. CONCLUSIONS:
      These results demonstrate the feasibility of an antithrombotic strategy based on
      ribozyme technology.

PMID- 12010912
TI  - Importance of NAD(P)H oxidase-mediated oxidative stress and contractile type
      smooth muscle myosin heavy chain SM2 at the early stage of atherosclerosis.
AB  - BACKGROUND: Increased vascular oxidative stress induced by hyperlipidemia may
      alter the phenotype of vascular smooth muscle (SM) cells and play a crucial role
      in the progression of atherosclerosis. To clarify the mechanisms underlying
      vascular dysfunction and oxidative stress in hypercholesterolemia, we compared
      the effects of antioxidant probucol with those of pravastatin on aortic
      stiffness, phenotypic modulation, oxidative stress, and NAD(P)H oxidase essential
      subunit p22(phox) expression in aortic medial SM cells of cholesterol-fed rabbits
      by using color image analysis of immunostained sections. METHODS AND RESULTS:
      Japanese white male rabbits were fed either normal chow or 1% cholesterol diet
      for 14 weeks. After the first 7 weeks, cholesterol-fed rabbits were further
      divided into 3 groups: those fed with cholesterol feed only and those
      additionally given pravastatin (10 mg/d) or probucol (1.3 g/d) for the last 7
      weeks. Within 7 weeks of treatment, probucol improved aortic stiffness more
      effectively than did pravastatin, inhibiting phenotypic modulation by selectively
      upregulating contractile-type SM myosin heavy chain isoform SM2 and by reducing
      both p22(phox) and superoxide content in medial SM cells of cholesterol-fed
      rabbit aorta. No significant differences in cholesterol levels, superoxide
      content, and endothelial NO synthase levels in the intima, aortic morphology and
      fibrosis, and synthetic-type myosin heavy chain in medial SM cells were observed
      between the 2 drug-treated groups. CONCLUSIONS: These results suggest that
      oxidative stress and SM2 in medial SM cells might be important factors for
      vascular dysfunction, and strategies aimed at blocking NAD(P)H oxidase and
      upregulating SM2 may have therapeutic potential against the progression of
      atherosclerosis in hypercholesterolemia.

PMID- 12010913
TI  - Structure, endothelial function, cell growth, and inflammation in blood vessels
      of angiotensin II-infused rats: role of peroxisome proliferator-activated
      receptor-gamma.
AB  - BACKGROUND: Pioglitazone and rosiglitazone, thiazolidinedione peroxisome
      proliferator-activated receptor-gamma (PPARgamma) activators, reduce blood
      pressure (BP) in some hypertensive models by unclear mechanisms. We tested the
      hypothesis that pioglitazone or rosiglitazone would prevent BP elevation and
      vascular dysfunction in angiotensin (Ang) II-infused rats by direct vascular
      effects. METHODS AND RESULTS: Sprague-Dawley rats received Ang II (120 ng x kg(
      1) x min(-1) SC) with or without pioglitazone (10 mg x kg(-1) x d(-1)) or
      rosiglitazone (5 mg x kg(-1) x d(-1)) for 7 days. Systolic BP, elevated in Ang II
      infused rats (176+/-5 mm Hg) versus controls (109+/-2 mm Hg, P<0.01), was reduced
      by pioglitazone (134+/-2 mm Hg) or rosiglitazone (123+/-2 mm Hg). In mesenteric
      small arteries studied in a pressurized myograph, media/lumen ratio was increased
      (P<0.05) and acetylcholine-induced relaxation impaired in Ang II-infused rats
      (P<0.05); both were normalized by the thiazolidinediones. In Ang II-infused rats,
      vascular DNA synthesis (by 3H-thymidine incorporation); expression of cell cycle
      proteins cyclin D1 and cdk4, angiotensin II type 1 receptors, vascular cell
      adhesion molecule-1, and platelet and endothelial cell adhesion molecule; and
      nuclear factor-kappaB activity were increased. These changes were abrogated by
      pioglitazone or rosiglitazone. CONCLUSIONS: Thiazolidinedione PPAR-gamma
      activators attenuated the development of hypertension, corrected structural
      abnormalities, normalized cell growth, and improved endothelial dysfunction
      induced by Ang II and prevented upregulation of angiotensin II type 1 receptors,
      cell cycle proteins, and proinflammatory mediators. Thiazolidinediones may be
      useful in the prevention and/or treatment of hypertension, particularly when it
      is associated with insulin resistance or diabetes mellitus.

PMID- 12010914
TI  - Cardiac membrane fatty acid composition modulates myocardial oxygen consumption
      and postischemic recovery of contractile function.
AB  - BACKGROUND: Regular fish consumption is associated with low cardiovascular
      disease morbidity and mortality. Fish oils modify cardiac membrane phospholipid
      fatty acid composition with potent antiarrhythmic effects. We tested the effects
      of dietary fish oil on ventricular hemodynamics and myocardial oxygen consumption
      (MVO2). METHODS AND RESULTS: Male Wistar rats were fed for 16 weeks on a
      reference diet rich in n-6 polyunsaturated fatty acids (PUFA), a diet rich in
      saturated animal fat (SAT), or a diet rich in n-3 PUFA from fish oil. Isolated
      working hearts were perfused with porcine erythrocytes (40% hematocrit) at 75 mm
      Hg afterload with variable preload (5 to 20 mm Hg) or with low coronary flow
      ischemia with maintained afterload, preload, and heart rate, then reperfused.
      MVO2 was low and coronary perfusion reserve high in n-3 PUFA hearts, and cardiac
      output increased with workload. The n-3 PUFA reduced ischemic markers-acidosis,
      K+, lactate, and creatine kinase-and increased contractile recovery during
      reperfusion. SAT hearts had high MVO2, low coronary perfusion reserve, and poor
      contractile function and recovery. Dietary differences in MVO2 were abolished by
      KCl arrest (basal metabolism) or ruthenium red (3.4 micromol/L) but not by
      ryanodine (1 nmol/L). Fish oil or ryanodine, but not ruthenium red, prevented
      ventricular fibrillation in reperfusion. CONCLUSIONS: Dietary fish oil directly
      influenced heart function and improved cardiac responses to ischemia and
      reperfusion. The n-3 PUFA reduced oxygen consumption at any given work output and
      increased postischemic recovery. Thus, direct effects on myocardial function may
      contribute to the altered cardiovascular disease profile associated with fish
      consumption.

PMID- 12010915
TI  - Effects of pinacidil on electrophysiological properties of epicardial border zone
      of healing canine infarcts: possible effects of K(ATP) channel activation.
AB  - BACKGROUND: K(ATP) channels, activated by ischemia, participate in the
      arrhythmogenic response to acute coronary occlusion. The function of these
      channels in border zones of healing infarcts, where arrhythmias also arise, has
      not been investigated. Do these channels remain maximally activated during
      infarct healing, or do they downregulate after a period of time? Both might
      preclude further activation. METHODS AND RESULTS: Myocardial infarction was
      produced in dogs by ligation of the left anterior descending coronary artery.
      Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing
      infarcts was mapped during administration of pinacidil, a K(ATP) channel
      activator, directly into the EBZ coronary blood supply. Pinacidil restored
      conduction and excitability when the EBZ was initially inexcitable and had large
      regions of block (6 of 8 experiments). This allowed reentrant circuits to form in
      the EBZ, causing tachycardia (4 of 8 experiments). In hearts with an initially
      excitable EBZ, pinacidil shortened the effective refractory period and abolished
      conduction block at short cycle lengths (7 experiments). This effect prevented
      initiation of reentry (1 of 2 experiments). CONCLUSIONS: The response to
      pinacidil indicates that K(ATP) channels in the EBZ remain functional and can be
      activated to influence electrophysiological properties and arrhythmogenesis.

PMID- 12010916
TI  - Collaborative care for adults with congenital heart disease.

PMID- 12010917
TI  - Images in cardiovascular medicine. Temporal and spatial changes in left
      ventricular pattern of flow during continuous assist device "HeartMate II".

PMID- 12010918
TI  - Images in cardiovascular medicine. Truncus arteriosus and double aortic arch.

PMID- 12010919
TI  - Transmyocardial and percutaneous myocardial laser revascularization.

PMID- 12010920
TI  - Inverse relationship between volume and outcome in coronary angioplasty: what are
      the implications for clinical practice?

PMID- 12010921
TI  - Myocardial and cerebral injury after off-pump coronary artery surgery.

PMID- 12010922
TI  - Promotion of collateral growth by granulocyte-macrophage colony-stimulating
      factor in patients with coronary artery disease.

PMID- 12010924
TI  - Current and future relevance of guidelines.

PMID- 12010925
TI  - Some reflections on how not to get bitten by a clinical guideline.

PMID- 12010926
TI  - Attitudinally correct nomenclature.

PMID- 12010927
TI  - Myocardial dysfunction in sepsis: no role for NO?

PMID- 12010928
TI  - History of cardiac surgery.

PMID- 12010929
TI  - NICE: guessing is not guidance. National Institute for Clinical Excellence.
AB  - A preliminary assessment of the extent to which the National Institute for
      Clinical Excellence (NICE) has achieved its goals within cardiovascular medicine
      is presented. NICE is a government sponsored agency operating in the UK which
      attempts to assess the value of medical therapies, devices, and surgery for a
      wide range of medical and surgical problems. Its recommendations determine
      whether a particular therapy can be adopted in the National Health Service.

PMID- 12010930
TI  - Central neural contribution to the perception of chest pain in cardiac syndrome
      X.
AB  - OBJECTIVE: To investigate the central neural contribution to chest pain
      perception in cardiac syndrome X (angina-like pain, ECG changes during stress,
      angiographically normal coronary arteriogram). SUBJECTS: Eight syndrome X
      patients and eight healthy volunteers. METHODS: Dobutamine stress using
      echocardiography to assess myocardial function, and positron emission tomography
      to measure changes in regional cerebral blood flow, as an index of neuronal
      activity. RESULTS: During similar doses of dobutamine, syndrome X patients and
      controls showed comparable regional cerebral blood flow changes in the
      hypothalamus, thalami, right orbito-frontal cortex, and anterior temporal poles,
      associated with the sensation of a fast or powerful heart beat. In patients, but
      not controls, the stress also generated severe chest pain associated with
      increased activity in the right anterior insula/frontal operculum junction. There
      were ischaemia-like ECG changes in the syndrome X patients, but no left
      ventricular dysfunction on echocardiography. Activation of the right insula
      during chest pain clearly distinguished the syndrome X patients from a group of
      patients with known coronary disease. CONCLUSIONS: Chest pain and ECG changes
      were not accompanied by demonstrable myocardial dysfunction in syndrome X
      patients, but altered central neural handling of afferent signals may contribute
      to the abnormal pain perception in these patients.

PMID- 12010931
TI  - Troponin T concentrations 72 hours after myocardial infarction as a serological
      estimate of infarct size.
AB  - BACKGROUND: After acute myocardial infarction, the structural protein T is
      released considerably longer than cytosolic creatine kinase (CK), CK MB isoenzyme
      (CK-MB), or lactate dehydrogenase (LDH) and late troponin T release (> 48 hours
      after onset of chest pain) appears to be less affected by early coronary
      reperfusion. OBJECTIVE: To investigate the precision of a single measurement of
      circulating troponin T concentrations 72 hours after onset of chest pain compared
      with standard scintigraphic and enzymatic estimates of myocardial infarct size.
      METHODS: Quantitative single photon emission computed tomography thallium-201
      scintigraphy at rest was performed in 37 patients 2-3 weeks after myocardial
      infarction (group 1: 14 patients without early coronary reperfusion; group 2: 23
      patients with early reperfusion achieved by thrombolytic therapy, by percutaneous
      transluminal coronary angioplasty, or by both). RESULTS: In both groups, the
      number of myocardial segments with abnormal thallium-201 uptake indicating the
      individual extent of irreversible myocardial damage correlated significantly with
      the troponin T concentrations 72 hours after infarction as well as with peak
      concentrations of CK, CK-MB, and LDH. CONCLUSION: The data show that a single
      measurement of circulating troponin T 72 hours after onset of chest pain-
      independent of reperfusion--is superior for the estimation of myocardial infarct
      size to measurement of peak CK, CK-MB, or LDH, which require serial
      determinations and depend on coronary reperfusion.

PMID- 12010932
TI  - Evidence for association of a common variant of the endothelial nitric oxide
      synthase gene (Glu298-->Asp polymorphism) to the presence, extent, and severity
      of coronary artery disease.
AB  - BACKGROUND: Genetic variants of endothelial nitric oxide synthase (eNOS) could
      influence individual susceptibility to coronary artery disease. OBJECTIVE: To
      assess whether Glu298-->Asp polymorphism of the eNOS gene is associated with the
      occurrence and severity of angiographically defined coronary artery disease in
      the Italian population. METHODS: Polymerase chain reaction/restriction fragment
      length polymorphism analysis was done to detect the Glu298-->Asp variant of the
      eNOS gene in 201 patients with coronary artery disease and 114 controls. The
      severity of coronary artery disease was expressed by the number of affected
      vessels and by the Duke scoring system. RESULTS: The frequencies of the eNOS
      Glu/Glu, Glu/Asp, and Asp/Asp genotypes in the coronary artery disease group were
      significantly different from those of controls (45.3%, 38.8%, and 15.9% v 42.1%,
      51.8%, and 6.1%, respectively; chi2 = 8.589, p = 0.0136). In comparison with
      subjects who had a Glu298 allele in the eNOS gene, the risk of coronary artery
      disease was increased among Asp/Asp carriers (odds ratio 2.9, 95% confidence
      interval 1.2 to 6.8, p = 0.01) and was independent of the other common risk
      factors (p = 0.04). There was a significant association between the eNOS Glu298-
      >Asp variant and both the number of stenosed vessels (mean (SEM), 2.3 (0.1) for
      Asp/Asp v 1.9 (0.1) and 1.8 (0.1) for Glu/Glu and Glu/Asp, respectively; p =
      0.01) and the Duke score (56.1 (3.1) for Asp/Asp v 46.7 (2.0) and 46.1 (1.9) for
      Glu/Glu and Glu/Asp, respectively; p = 0.02). CONCLUSIONS: Glu298-->Asp
      polymorphism of the eNOS gene appears to be associated with the presence, extent,
      and severity of angiographically assessed coronary artery disease.

PMID- 12010933
TI  - Comparison of permanent left ventricular and biventricular pacing in patients
      with heart failure and chronic atrial fibrillation: prospective haemodynamic
      study.
AB  - OBJECTIVE: To compare clinical and haemodynamic variables between left
      ventricular and biventricular pacing in patients with severe heart failure; and
      to analyse haemodynamic changes during daily life and maximum exercise during
      chronic left ventricular and biventricular pacing. DESIGN: Prospective single
      blinded randomised study with crossover. SETTING: University hospital (tertiary
      referral centre). PATIENTS AND METHODS: 13 patients (mean (SD) age, 62 (6) years)
      with chronic atrial fibrillation, severe heart failure (mean ejection fraction 24
      (8)%), and QRS prolongation of > or = 140 ms had His bundle ablation and
      installation of a pacemaker providing left ventricular and biventricular pacing.
      The pacemaker was equipped with a peak endocardial acceleration (PEA) sensor. The
      PEA pattern was used as a haemodynamic marker during exercise as it is highly
      correlated with left ventricular dP/dt. After a baseline period of right
      ventricular pacing, all patients had two months of left ventricular pacing and
      two months of biventricular pacing in random order. At the end of each phase, an
      echocardiogram, a haemodynamic analysis at rest and on exercise during a six
      minute walk test, and a cardiopulmonary exercise test were performed. RESULTS:
      PEA values were higher with left ventricular pacing (0.58 (0.38) m/s) and
      biventricular pacing (0.62 (0.24) m/s) than at baseline (0.49 (0.18) m/s) (p <
      0.05). The six minute walk test showed similar performance in both pacing modes,
      but patients had more symptoms with left ventricular pacing at the end of the
      test (p = 0.035). On cardiopulmonary exercise testing, there was a greater
      increase in mean percentage variation of PEA with biventricular pacing than with
      left ventricular pacing (125 (18)% v 97 (36)%, respectively; p = 0.048) and
      better performance figures (92 (34) W v 77 (23) W; p = 0.03). CONCLUSIONS: During
      symptom limited and daily life exercise tests, chronic biventricular pacing
      provides better haemodynamic performance than left ventricular pacing. In heart
      failure patients with wide QRS complexes, the interventricular dyssynchronisation
      induced by left ventricular pacing may impair myocardial function during
      exercise.

PMID- 12010935
TI  - Intermittent Brugada syndrome misdiagnosed as acute myocardial infarction and
      unmasked with propafenone.

PMID- 12010936
TI  - Isolated left main coronary artery stenosis: long term follow up in 106 patients
      after surgery.
AB  - OBJECTIVE: To analyse the long term prognosis in patients with isolated stenoses
      of the left main coronary artery (LMCA) following surgical revascularisation.
      PATIENTS: 106 patients (71 men and 35 women, mean age 61 years) were operated on
      between 1982 and 1998. Before surgery, 103 patients presented with angina
      pectoris and only 10 had a history of myocardial infarction. Their mean left
      ventricular ejection fraction was 62%. Stenoses were localised on the LMCA ostium
      in 19 patients, a subgroup characterised by a high proportion of women (68%).
      Three patients presented with chronic LMCA occlusion. Forty six patients were
      operated on as an emergency. The mean (SD) number of grafts per patient was 2.0
      (0.5), and only one patient had no left anterior descending (LAD) coronary artery
      bypass. Bypass of the LAD using the internal thoracic artery was performed in 88
      cases. RESULTS: Early postoperative mortality was 4.7% and the five year survival
      was 86.8%. Late mortality occurred in nine cases, and in three of these it was
      linked to a coronary condition. Of the 92 long term survivors, 81.5% were totally
      symptom-free and 77% of those of working age were able to resume work. The
      postoperative outcome of patients with isolated ostial LMCA stenosis did not
      differ significantly from that of the other patients. CONCLUSIONS: The
      postoperative prognosis of isolated LMCA stenosis appears good in terms of
      mortality and symptoms.

PMID- 12010934
TI  - Meta-analysis of randomised controlled trials of the effectiveness of
      antiarrhythmic agents at promoting sinus rhythm in patients with atrial
      fibrillation.
AB  - OBJECTIVE: To conduct a meta-analysis of randomised controlled trials to estimate
      the effectiveness of antiarrhythmic drugs at promoting sinus rhythm in patients
      with atrial fibrillation. DESIGN: Articles were identified by using a
      comprehensive search of English language papers indexed in Medline from 1966 to
      August 2001. For the outcomes of sinus rhythm and death, a random effects model
      was used to model repeated assessments within a study at different time points.
      SETTING: Emergency departments and ambulatory clinics. PATIENTS: Patients with
      atrial fibrillation. INTERVENTIONS: Antiarrhythmic agents grouped according to
      their Vaughan-Williams class. MAIN OUTCOME MEASURES: Sinus rhythm and mortality.
      RESULTS: 91 articles met a priori criteria for inclusion in the analysis. Median
      duration of follow up was one day (range 0.04-1096, mean (SD) 46 (136) days). The
      median proportion of patients in sinus rhythm at follow up was 55% (range 0-100%)
      and 32% (range 0-90%) receiving active treatment and placebo, respectively.
      Median survival was 99% (range 55-100%) and 99% (range 55-100%). Compared with
      placebo, the following drug classes were associated with increased sinus rhythm
      at follow up: IA (treatment difference 21.5%, 95% confidence interval (CI) 16.3%
      to 26.8%); IC (treatment difference 33.1%, 95% CI 23.3% to 42.9%); and III
      (treatment difference 17.4%, 95% CI 11.5% to 23.3%). Class IC drugs were
      associated with increased sinus rhythm at follow up compared with class IV drugs
      (treatment difference 43.2%, 95% CI 11.5% to 75.0%). There was no significant
      difference in mortality between any drug classes. CONCLUSIONS: Class IA, IC, and
      III drugs are associated with increased sinus rhythm at follow up compared with
      placebo. It is unclear whether any antiarrhythmic drug class is associated with
      increased or decreased mortality.

PMID- 12010938
TI  - Cardiac involvement in idiopathic hypereosinophilic syndrome.

PMID- 12010937
TI  - Prognostic implication of cardiac troponin T increase following stent
      implantation.
AB  - OBJECTIVE: To identify the incidence and clinical significance of myocardial
      injury following elective stent implantation. DESIGN: Prospective clinical study
      with 278 consecutive patients undergoing stenting of de novo coronary or
      saphenous vein graft lesions. Incidence of periprocedural myocardial injury was
      assessed by analysis of 12 lead ECG, creatine kinase (CK; upper limit of normal
      (ULN) 70 IU/l for women, 80 IU/l for men), and cardiac troponin T (cTnT; point of
      care test; threshold 0.1 ng/ml) before and 6, 12, and 24 hours after the
      intervention. Major adverse cardiac events (MACE: acute myocardial infarction,
      bypass surgery, and cardiac death) were recorded during clinical follow up (mean
      (SD) 7.8 (5.3) months). RESULTS: Following elective stenting, the rate of a
      positive cTnT status was 17.3%, the rate of CK increase of 1-3x ULN 14.7%, the
      rate of CK increase of > 3x ULN 1.4%, and the rate of Q wave myocardial
      infarction 0.4%. Cardiac mortality during follow up was higher in patients with
      postprocedurally increased CK (7.1% v 1.3%, p = 0.01, log rank) and cTnT (9.1% v
      0.9%, p < 0.001, log rank). In addition, postprocedurally increased cTnT was
      associated with a higher overall incidence of MACE (13.1% v 4.0%, p < 0.01, log
      rank) and was identified as an independent factor for MACE during follow up
      (hazard ratio 3.27, 95% confidence interval 1.14 to 9.41, p = 0.028).
      CONCLUSIONS: Following elective stent implantation, a positive cTnT status
      identified patients at risk of a worse long term outcome. Treatment strategies
      have to be developed that lead to prognostic improvement by reducing
      periprocedural myocardial injury.

PMID- 12010940
TI  - Gastric perforation complicating direct current cardioversion.

PMID- 12010939
TI  - Flow during exercise in the total cavopulmonary connection measured by magnetic
      resonance velocity mapping.
AB  - OBJECTIVE: To measure caval and pulmonary flows at rest and immediately after
      exercise in patients with total cavopulmonary connection (TCPC). DESIGN: An
      observational study using the patients as their own controls. SETTING: Using a
      combination of magnetic resonance (MR) phase contrast techniques and an MR
      compatible bicycle ergometer, blood flow was measured in the superior vena cava,
      the tunnel from the inferior vena cava, and in the left and right pulmonary
      arteries during rest and on exercise (0.5 W/kg and 1.0 W/kg). PATIENTS: Eleven
      patients aged 11.4 (4.6) years (mean (SD)) were studied 6.3 (3.8) years after
      TCPC operation. MAIN OUTCOME MEASURES: Volume flow measured in all four branches
      of the TCPC connection during rest and exercise. RESULTS: Systemic venous return
      (inferior vena cava plus superior vena cava) increased from 2.5 (0.1) l/min/m2
      (mean (SEM)) to 4.4 (0.4) l/min/m2 (p < 0.05) during exercise, with even
      distribution to the two pulmonary arteries. At rest, inferior vena caval flow was
      higher than superior vena caval flow, at 1.4 (0.1) v 1.1 (0.1) l/min/m2 (p <
      0.05). During exercise, inferior vena caval flow doubled (to 3.0 (0.3) l/min/m2)
      while superior vena caval flow only increased slightly (to 1.4 (0.1) l/min/m2) (p
      < 0.05). The increased blood flow mainly reflected an increase in heart rate. The
      inferior vena caval to superior vena caval flow ratio was 1.4 (0.1) at rest and
      increased to 1.8 (0.1) (p < 0.05) at 0.5 W/kg, and to 2.2 (0.2) at 1.0 W/kg (p <
      0.05). CONCLUSIONS: Quantitative flow measurements can be performed immediately
      after exercise using MR techniques. Supine leg exercise resulted in a more than
      twofold increase in inferior vena caval flow. This was equally distributed to the
      two lungs, indicating that pulmonary resistance rather than geometry decides flow
      distribution in the TCPC circulation.

PMID- 12010941
TI  - Non-invasive measurement of coronary flow reserve in children with Kawasaki
      disease.
AB  - OBJECTIVE: To investigate whether transthoracic Doppler echocardiography (TTE)
      can reliably measure the coronary flow reserve in the left anterior descending
      coronary artery in children with Kawasaki disease. DESIGN: Coronary flow velocity
      in the distal left anterior descending coronary artery was measured by TTE and
      was compared with that obtained by intracoronary Doppler guide wire. The ratio of
      maximum hyperaemia (intravenous administration of adenosine triphosphate, 160
      microg/kg/min) to baseline peak (mean) diastolic coronary flow velocity in the
      distal artery was used as an estimate of coronary flow reserve. SETTING:
      University hospital. PATIENTS: 10 patients with significant left anterior
      descending coronary stenosis (> 70% diameter stenosis) (group A) in the proximal
      or middle portion of the artery and 14 patients (group B) without significant
      stenosis, all with Kawasaki disease documented by previous coronary angiography.
      RESULTS: The reduced hyperaemic coronary flow velocity in group A compared with
      group B resulted in a markedly lower coronary flow reserve, derived from both
      peak diastolic velocity and mean diastolic velocity by either technique of
      investigation. Multivariate analysis identified the best predictor of left
      anterior descending coronary artery stenosis to be a coronary flow reserve of <
      or = 2.2, derived from mean diastolic flow velocity measured using TTE
      (sensitivity 90%, specificity 100%, accuracy 96%). A good correlation was found
      between diastolic velocity derived values for coronary flow reserve measured
      using both TTE and Doppler guide wire (r = 0.92, p = 0.0001). CONCLUSIONS:
      Coronary flow reserve in the distal left anterior descending coronary artery can
      be accurately measured using TTE without any intravascular instrumentation in
      children with Kawasaki disease.

PMID- 12010942
TI  - Biventricular hypertrophic cardiomyopathy with lone obstruction to right
      ventricular outflow.

PMID- 12010943
TI  - Dual chamber pacing in patients with severe heart failure on beta blocker and
      amiodarone treatment: preliminary results of a randomised study.

PMID- 12010944
TI  - Post-infarction ventricular septal defect with aneurysm.

PMID- 12010945
TI  - Histological gap between ablation lesions detected by phased array intracardiac
      echocardiography.

PMID- 12010946
TI  - Familial Mediterranean fever gene (MEFV) mutations in patients with rheumatic
      heart disease.

PMID- 12010947
TI  - Left ventricular pseudoaneurysm: a mechanical complication of acute myocardial
      infarction.

PMID- 12010948
TI  - To whom do the research findings apply?

PMID- 12010949
TI  - Novel mapping techniques for cardiac electrophysiology.

PMID- 12010950
TI  - Choice of heart valve prosthesis.

PMID- 12010954
TI  - Beneficial effects of biventricular pacing in a patient with hypertrophic
      cardiomyopathy and intraventricular conduction delay.
AB  - The beneficial use of biventricular pacing is reported in a patient with
      hypertrophic cardiomyopathy and intraventricular conduction delay. This resulted
      in improvements in symptomatic status and exercise tolerance that may be related
      to cardiac resynchronisation. The improvement in symptoms by biventricular pacing
      in a patient with hypertrophic cardiomyopathy and intraventricular conduction
      delay is previously undocumented and requires further investigation.

PMID- 12010955
TI  - Diagnosis of amyloidosis by histological examination of subcutaneous fat sampled
      at the time of pacemaker implantation.
AB  - Atrioventricular conduction disease may occur in a range of conditions. If
      echocardiography suggests the presence of an infiltrative cardiomyopathy the
      diagnosis of amyloidosis may be confirmed by subcutaneous fat sampling from the
      site of pacemaker implantation. This technique requires no additional invasive
      procedure and confers no extra risk for the patient. Confirmation of amyloidosis
      provides important prognostic information and may allow specific treatment.

PMID- 12010956
TI  - Mitral valve endocarditis in hypertrophic cardiomyopathy: case report and
      literature review.
AB  - Mitral endocarditis complicating hypertrophic cardiomyopathy occurs predominantly
      on the left ventricular aspect of the anterior mitral valve leaflet in the
      presence of outflow tract obstruction. It is a rare condition and the estimated
      cumulative 10 year probability of developing endocarditis in patients with
      obstruction is < 5%. Combined mitral valve replacement and septal myectomy has
      been reported in this setting. A case of community acquired Staphylococcus aureus
      mitral valve endocarditis is reported in a previously asymptomatic young man with
      hypertrophic obstructive cardiomyopathy. The potential treatment options are
      discussed.

PMID- 12010958
TI  - Immunity to murine chlamydial genital infection.

PMID- 12010959
TI  - A lytic transglycosylase of Neisseria gonorrhoeae is involved in peptidoglycan
      derived cytotoxin production.
AB  - Neisseria gonorrhoeae releases soluble fragments of peptidoglycan during growth.
      These molecules are implicated in the pathogenesis of various forms of gonococcal
      infection. A major peptidoglycan fragment released by gonococci is identical to
      the tracheal cytotoxin of Bordetella pertussis and has been shown to kill
      ciliated fallopian tube cells in organ culture. Previous studies indicated that a
      unique lytic peptidoglycan transglycosylase (AtlA) was responsible for some, but
      not all, of the peptidoglycan-derived cytotoxin (PGCT) production in certain
      gonococcal strains. To examine the role of other putative lytic transglycosylases
      in PGCT production, we made a deletion mutation in a gonococcal gene exhibiting
      similarity with genes encoding lytic transglycosylases from other bacterial
      species. The gonococcal mutant was viable and grew normally, but it was less
      autolytic than the wild-type strain in stationary-phase culture and under
      nongrowth conditions. The gonococcal mutant was reduced in peptidoglycan
      turnover, and the profile of the released products showed a reduction in
      monomeric peptidoglycan. Proportionally more multimeric fragments were released.
      These results suggest that this gonococcal gene (ltgA) encodes a lytic
      peptidoglycan transglycosylase and that it is responsible for a significant
      proportion of the PGCT released by N. gonorrhoeae.

PMID- 12010960
TI  - Transcription of clumping factor A in attached and unattached Staphylococcus
      aureus in vitro and during device-related infection.
AB  - Staphylococcus aureus is one of the pathogens most frequently isolated in device
      related infections. S. aureus is equipped with surface-associated proteins
      promoting specific binding to matrix molecules. Clumping factor A (ClfA, encoded
      by clfA) mediates adhesion to fibrinogen. Whereas the contribution of ClfA to
      pathogenicity is well documented, the influence of different growth and host
      parameters on gene activity is unclear. To elucidate this question, we
      investigated clfA transcript levels in an animal model of device-related
      infection and in planktonic and sessile bacteria grown in vitro. Specific mRNA
      from the S. aureus strains Newman, Reynolds, and RN6390 was quantified by
      LightCycler reverse transcription-PCR. In vitro, clfA transcript levels were low
      in the early logarithmic growth phase, but a clear increase was observed after
      the late logarithmic phase. Quantities of clfA transcripts were four to six times
      higher in the planktonic than in the sessile bacterial subpopulations grown to
      the stationary phase. During infection, in strains Newman and Reynolds levels of
      clfA transcripts in exudates accumulating in the infected devices were lower than
      those in the bacteria grown in vitro to stationary phase. clfA mRNA levels in the
      exudates increased during the initial phase of infection and remained constant
      after 96 h postinoculation. In contrast to the in vitro results, quantities of
      clfA transcripts in the unattached bacteria of the exudates never exceeded the
      level of clfA transcripts in the sessile bacteria attached to glass beads.
      However, a clear increase in clfA quantities in the sessile bacteria was observed
      late in infection after 144 h. In conclusion, maximal clfA transcript levels are
      reached late during growth in vitro and in vivo.

PMID- 12010961
TI  - Mapping and sequencing of the canine NRAMP1 gene and identification of mutations
      in leishmaniasis-susceptible dogs.
AB  - The NRAMP1 gene (Slc11a1) encodes an ion transporter protein involved in the
      control of intraphagosomal replication of parasites and in macrophage activation.
      It has been described in mice as the determinant of natural resistance or
      susceptibility to infection with antigenically unrelated pathogens, including
      Leishmania. Our aims were to sequence and map the canine Slc11a1 gene and to
      identify mutations that may be associated with resistance or susceptibility to
      Leishmania infection. The canine Slc11a1 gene has been mapped to dog chromosome
      CFA37 and covers 9 kb, including a 700-bp promoter region, 15 exons, and a
      polymorphic microsatellite in intron 1. It encodes a 547-amino-acid protein that
      has over 87% identity with the Slc11a1 proteins of different mammalian species. A
      case-control study with 33 resistant and 84 susceptible dogs showed an
      association between allele 145 of the microsatellite and susceptible dogs.
      Sequence variant analysis was performed by direct sequencing of the cDNA and the
      promoter region of four unrelated beagles experimentally infected with Leishmania
      infantum to search for possible functional mutations. Two of the dogs were
      classified as susceptible and the other two were classified as resistant based on
      their immune responses. Two important mutations were found in susceptible dogs: a
      G-rich region in the promoter that was common to both animals and a complete
      deletion of exon 11, which encodes the consensus transport motif of the protein,
      in the unique susceptible dog that needed an additional and prolonged treatment
      to avoid continuous relapses. A study with a larger dog population would be
      required to prove the association of these sequence variants with disease
      susceptibility.

PMID- 12010962
TI  - In vivo expression and immunological studies of the 42-kilodalton carboxyl
      terminal processing fragment of Plasmodium falciparum merozoite surface protein 1
      in the baculovirus-silkworm system.
AB  - The 42-kDa carboxyl-terminal processing fragment of Plasmodium falciparum
      merozoite surface protein 1 (MSP-1(42)) is an anti-erythrocytic stage malaria
      vaccine candidate. In this study, MSP-1(42) was expressed by using the Bombyx
      mori nuclear polyhedrosis virus-silkworm expression system, and the antigenicity
      and immmunogenicity of the recombinant protein, Bmp42, were evaluated. The
      average yield of Bmp42, as determined by a sandwich enzyme-linked immunosorbent
      assay (ELISA), was 379 microg/ml of infected silkworm hemolymph, which was >100
      fold higher than the level attainable in cell culture medium. N-terminal amino
      acid sequencing revealed that Bmp42 was correctly processed in silkworm cells.
      Data from immunoblotting, as well as from the inhibition ELISA, suggested that
      the conformational B-cell epitopes of MSP-1(42) were recreated in Bmp42.
      Immunization of rabbits with Bmp42 in complete Freund's adjuvant generated high
      titer antibody responses against the immunogen. Specificity analyses of the anti
      Bmp42 antibodies using several recombinant MSP-1(19) proteins expressing variant
      and conserved B-cell epitopes suggested that the anti-Bmp42 antibodies recognized
      primarily conserved epitopes on MSP-1(19). Furthermore, the anti-Bmp42 antibodies
      were highly effective in inhibiting the in vitro growth of parasites carrying
      homologous or heterologous MSP-1(42). Our results demonstrated that the
      baculovirus-silkworm expression system could be employed to express biologically
      and immunologically active recombinant MSP-1(42) at elevated levels; thus, it is
      an attractive alternative for producing a protective MSP-1(42) vaccine for human
      use.

PMID- 12010963
TI  - Monocyte differentiation in localized juvenile periodontitis is skewed toward the
      dendritic cell phenotype.
AB  - Several lines of evidence indicate that the monocytes of subjects with localized
      juvenile periodontitis (LJP) are functionally distinct from cells of age- and
      race-matched nonperiodontitis (NP) subjects. Among the abnormalities are the
      propensity to secrete large amounts of prostaglandin E(2) and the induction of
      immunoglobulin G2 (IgG2) antibodies. The experiments described here were
      performed to further characterize the LJP monocytes and to determine if these
      cells mature differently than NP monocytes. When adherent monocytes from LJP
      subjects were cultured in the presence of human serum, both macrophages and cells
      with the morphology of immature monocyte-derived dendritic cells (MDDC) were
      observed. Within 4 days the prevalence of the immature MDDC was approximately
      twofold higher in LJP cultures than in NP cultures. In addition to their
      dendritic morphology, these cells were CD11c(+) and CD14(-) or CD14(low) and
      stimulated potent autologous mixed leukocyte reactions, consistent with
      differentiation to the MDDC phenotype. Like LJP monocytes, cultures of MDDC
      generated with interleukin-4 and granulocyte-macrophage colony-stimulating factor
      selectively induced IgG2 in cultures of pokeweed mitogen-stimulated NP
      leukocytes. Together, these data suggest that the monocytes of LJP subjects have
      a propensity to differentiate into MDDC and that this differentiation may be
      related to the high levels of IgG2 that are observed in the sera of LJP subjects.
      As high levels of circulating IgG2 are correlated with less severe disease, the
      propensity of LJP monocytes to differentiate into MDDC may have important
      implications for both the host response against oral pathogens and the
      progression of LJP.

PMID- 12010964
TI  - Mycobacterium tuberculosis genes induced during infection of human macrophages.
AB  - We identified Mycobacterium tuberculosis genes preferentially expressed during
      infection of human macrophages using a promoter trap adapted for this pathogen.
      inhA encodes an enoyl-acyl carrier protein reductase that is required for mycolic
      acid biosynthesis (A. Quemard et al., Biochemistry 34:8235-8241, 1995) and is a
      major target for isoniazid (INH) in mycobacterial species (A. Banerjee et al.,
      Science 263:227-230, 1994). Since overexpression of inhA confers INH resistance
      in Mycobacterium smegmatis (Banerjee et al., Science 263:227-230, 1994), we
      designed a promoter trap based on this gene. A library of clones, containing
      small fragments of M. tuberculosis DNA cloned upstream of inhA in a plasmid
      vector, was electroporated into M. tuberculosis, and the resulting culture was
      used to infect the human monocytic THP-1 cell line. Selection was made for clones
      surviving INH treatment during infection but retaining INH sensitivity on plates.
      The DNA upstream of inhA was sequenced in each clone to identify the promoter
      driving inhA expression. Thirteen genes identified by this method were analyzed
      by quantitative reverse transcription-PCR (R. Manganelli et al., Mol. Microbiol.
      31:715-724, 1999), and eight of them were found to be differentially expressed
      from cultures grown in macrophages compared with broth-grown cultures. Several of
      these genes are presumed to be involved in fatty acid metabolism; one potentially
      codes for a unique DNA binding protein, one codes for a possible potassium
      channel protein, and the others code for proteins of unknown function. Genes
      which are induced during infection are likely to be significant for survival and
      growth of the pathogen; our results lend support to the view that fatty acid
      metabolism is essential for the virulence of M. tuberculosis.

PMID- 12010965
TI  - Differential cytokine and antibody responses to adult and larval stages of
      Onchocerca volvulus consistent with the development of concomitant immunity.
AB  - The possibility of concomitant immunity and its potential mechanisms in
      Onchocerca volvulus infection were examined by analyzing cytokine and antibody
      responses to infective larval (third-stage larvae [L3] and molting L3 [mL3]),
      adult female worm (F-OvAg), and skin microfilaria (Smf) antigens in infected
      individuals in a region of hyperendemicity in Cameroon as a function of age.
      Peripheral blood mononuclear cell interleukin 5 (IL-5) responses to F-OvAg and
      Smf declined significantly with age (equivalent to years of exposure to O.
      volvulus). In contrast, IL-5 secretion in response to L3 and mL3 remained
      elevated with increasing age. Gamma interferon responses to L3, mL3, and F-OvAg
      were low or suppressed and unrelated to age, except for responses to Smf in older
      subjects. IL-10 levels were uniformly elevated, regardless of age, in response to
      L3, mL3, and F-OvAg but not to Smf, for which levels declined with age. A total
      of 49 to 60% of subjects had granulocyte-macrophage colony-stimulating factor
      responses to all O. volvulus antigens unrelated to age. Analysis of levels of
      stage-specific immunoglobulin G3 (IgG3) and IgE revealed a striking, age
      dependent dissociation between antibody responses to larval antigens (L3 and a
      recombinant L3-specific protein, O. volvulus ALT-1) which were significantly
      increased or maintained with age and antibody responses to F-OvAg, which
      decreased. Levels of IgG1 to L3 and F-OvAg were elevated regardless of age, and
      levels of IgG4 increased significantly with age, although not to O. volvulus ALT
      1, which may have unique L3-specific epitopes. Immunofluorescence staining of
      whole larvae showed that total anti-L3 immunoglobulin levels also increased with
      the age of the serum donor. The separate and distinct cytokine and antibody
      responses to adult and infective larval stages of O. volvulus which are age
      related are consistent with the acquisition of concomitant immunity in infected
      individuals.

PMID- 12010966
TI  - The in vitro interaction of Streptococcus pyogenes with human pharyngeal cells
      induces a phage-encoded extracellular DNase.
AB  - The role lysogenic bacteriophage play in the pathogenesis of the host bacterium
      is poorly understood. In a previous study, we found that streptococcal coculture
      with human pharyngeal cells resulted in the induction of lysogenic bacteriophage
      as well as the phage-associated streptococcal pyrogenic exotoxin C (SpeC). In
      this study, we have determined that in addition to SpeC induction, a number of
      other streptococcal proteins are also released by the bacteria during coculture
      with pharyngeal cells. Among these, we identified and characterized a novel 27
      kDa secreted protein. Sequence analysis of this novel protein demonstrated it to
      be encoded by the same lysogenic bacteriophage which harbors speC. Protein
      sequence analysis revealed varied homologies with several streptococcal DNases.
      Further biochemical characterization of the recombinantly expressed protein
      verified it to be a divalent cation-dependent streptococcal phage-encoded DNase
      (Spd1). Although functionally distinct, SpeC and Spd1 are associated by a number
      of parameters, including genetic proximity and transcriptional regulation.
      Finally, we speculate on the induction of phage-encoded DNase (Spd1) enhancing
      the fitness of both bacteria and phage.

PMID- 12010967
TI  - Fc-dependent and Fc-independent opsonization of Cryptococcus neoformans by
      anticapsular monoclonal antibodies: importance of epitope specificity.
AB  - Monoclonal antibodies (MAbs) reactive with glucuronoxylomannan (GXM), the major
      capsular polysaccharide of the yeast Cryptococcus neoformans, produce distinct
      capsular reactions when viewed by differential interference contrast microscopy.
      These reactions depend on the epitope specificity of the antibody. Opsonic
      activities of immunoglobulin G1 (IgG1) MAbs that produce patterns termed rim and
      puffy were examined. Rim-pattern MAbs are reactive with an epitope shared by GXM
      serotypes A, B, C, and D. Puffy-pattern MAbs are reactive only with serotypes A
      and D. In phagocytosis assays, using serotype A cells and resident murine
      peritoneal macrophages, rim-pattern MAbs were markedly more opsonic than puffy
      pattern MAbs. F(ab')(2) fragments of rim-pattern MAbs were synergistic with heat
      labile factors in normal human serum for opsonization of the yeast. F(ab')(2)
      fragments of puffy-pattern MAbs were also synergistic with normal serum in
      opsonization but at a much lower level than fragments of rim-pattern MAbs. Normal
      serum alone was not opsonic. F(ab')(2) fragments of rim-pattern MAbs, but not
      puffy-pattern MAbs, stimulated phagocytosis of encapsulated cryptococci in the
      absence of serum. This serum-independent opsonic action of F(ab')(2) fragments
      was abrogated by pretreatment of macrophages with purified GXM, suggesting the
      involvement of a phagocyte GXM receptor. The results indicate that (i) there are
      multiple mechanisms by which anticapsular IgG MAbs facilitate phagocytosis of
      encapsulated cryptococci, (ii) some anti-GXM antibodies are opsonic in an Fc
      independent manner, and (iii) opsonic activity correlates with the capsular
      reaction and occurs in an epitope-specific manner.

PMID- 12010968
TI  - Regulation of antigen-specific immunoglobulin G subclasses in response to
      conserved and polymorphic Plasmodium falciparum antigens in an in vitro model.
AB  - Cytophilic antibodies (Abs) play a critical role in protection against Plasmodium
      falciparum blood stages, yet little is known about the parameters regulating
      production of these Abs. We used an in vitro culture system to study the subclass
      distribution of antigen (Ag)-specific immunoglobulin G (IgG) produced by
      peripheral blood mononuclear cells (PBMCs) from individuals exposed to P.
      falciparum or unexposed individuals. PBMCs, cultivated with or without cytokines
      and exogenous CD40/CD40L signals, were stimulated with a crude parasite extract,
      recombinant vaccine candidates derived from conserved Ags (19-kDa C terminus of
      merozoite surface protein 1 [MSP1(19)], R23, and PfEB200), or recombinant Ags
      derived from the polymorphic Ags MSP1 block 2 and MSP2. No P. falciparum-specific
      Ab production was detected in PBMCs from unexposed individuals. PBMCs from donors
      exposed frequently to P. falciparum infections produced multiple IgG subclasses
      when they were stimulated with the parasite extract but usually only one IgG
      subclass when they were stimulated with a recombinant Ag. Optimal Ab production
      required addition of interleukin-2 (IL-2) and IL-10 for all antigenic
      preparations. The IgG subclass distribution was both donor and Ag dependent and
      was only minimally influenced by the exogenous cytokine environment. In vitro IgG
      production and subclass distribution correlated with plasma Abs to some Ags
      (MSP1(19), R23, and MSP2) but not others (PfEB200 and the three MSP1 block 2
      derived Ags). Data presented here suggest that intrinsic properties of the
      protein Ag itself play a major role in determining the subclass of the Ab
      response, which has important implications for rational design of vaccine
      delivery.

PMID- 12010969
TI  - Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion proteins
      confers protection against Leishmania major infection in susceptible BALB/c mice.
AB  - We have recently shown that a cocktail containing two leishmanial recombinant
      antigens (LmSTI1 and TSA) and interleukin-12 (IL-12) as an adjuvant induces solid
      protection in both a murine and a nonhuman primate model of cutaneous
      leishmaniasis. However, because IL-12 is difficult to prepare, is expensive, and
      does not have the stability required for a vaccine product, we have investigated
      the possibility of using DNA as an alternative means of inducing protective
      immunity. Here, we present evidence that the antigens TSA and LmSTI1 delivered in
      a plasmid DNA format either as single genes or in a tandem digene construct
      induce equally solid protection against Leishmania major infection in susceptible
      BALB/c mice. Immunization of mice with either TSA DNA or LmSTI1 DNA induced
      specific CD4(+)-T-cell responses of the Th1 phenotype without a requirement for
      specific adjuvant. CD8 responses, as measured by cytotoxic-T-lymphocyte activity,
      were generated after immunization with TSA DNA but not LmSTI1 DNA. Interestingly,
      vaccination of mice with TSA DNA consistently induced protection to a much
      greater extent than LmSTI1 DNA, thus supporting the notion that CD8 responses
      might be an important accessory arm of the immune response for acquired
      resistance against leishmaniasis. Moreover, the protection induced by DNA
      immunization was specific for infection with Leishmania, i.e., the immunization
      had no effect on the course of infection of the mice challenged with an unrelated
      intracellular pathogen such as Mycobacterium tuberculosis. Conversely,
      immunization of BALB/c mice with a plasmid DNA that is protective against
      challenge with M. tuberculosis had no effect on the course of infection of these
      mice with L. major. Together, these results indicate that the protection observed
      with the leishmanial DNA is mediated by acquired specific immune response rather
      than by the activation of nonspecific innate immune mechanisms. In addition, a
      plasmid DNA containing a fusion construct of the two genes was also tested.
      Similarly to the plasmids encoding individual proteins, the fusion construct
      induced both specific immune responses to the individual antigens and protection
      against challenge with L. major. These results confirm previous observations
      about the possibility of DNA immunization against leishmaniasis and lend support
      to the idea of using a single polygenic plasmid DNA construct to achieve
      polyspecific immune responses to several distinct parasite antigens.

PMID- 12010970
TI  - Identification of the Pseudomonas aeruginosa 1244 pilin glycosylation site.
AB  - Previous work (P. Castric, F. J. Cassels, and R. W. Carlson, J. Biol. Chem.
      276:26479-26485, 2001) has shown the Pseudomonas aeruginosa 1244 pilin glycan to
      be covalently bound to a serine residue. N-terminal sequencing of pilin fragments
      produced from endopeptidase treatment and identified by reaction with a glycan
      specific monoclonal antibody indicated that the glycan was present between
      residue 75 and the pilin carboxy terminus. Further sequencing of these peptides
      revealed that serine residues 75, 81, 84, 105, 106, and 108 were not modified.
      Conversion of serine 148, but not serine 118, to alanine by site-directed
      mutagenesis, resulted in loss of the ability to carry out pilin glycosylation
      when tested in an in vivo system. These results showed the pilin glycan to be
      attached to residue 148, the carboxy-terminal amino acid. The carboxy-proximal
      portion of the pilin disulfide loop, which is adjacent to the pilin glycan, was
      found to be a major linear B-cell epitope, as determined by peptide epitope
      mapping analysis. Immunization of mice with pure pili produced antibodies that
      recognized the pilin glycan. These sera also reacted with P. aeruginosa 1244
      lipopolysaccharide as measured by Western blotting and enzyme-linked
      immunosorbent assay.

PMID- 12010971
TI  - NikR mediates nickel-responsive transcriptional induction of urease expression in
      Helicobacter pylori.
AB  - The important human pathogen Helicobacter pylori requires the abundant expression
      and activity of its urease enzyme for colonization of the gastric mucosa. The
      transcription, expression, and activity of H. pylori urease were previously
      demonstrated to be induced by nickel supplementation of growth media. Here it is
      demonstrated that the HP1338 protein, an ortholog of the Escherichia coli nickel
      regulatory protein NikR, mediates nickel-responsive induction of urease
      expression in H. pylori. Mutation of the HP1338 gene (nikR) of H. pylori strain
      26695 resulted in significant growth inhibition of the nikR mutant in the
      presence of supplementation with NiCl(2) at > or =100 microM, whereas the wild
      type strain tolerated more than 10-fold-higher levels of NiCl(2). Mutation of
      nikR did not affect urease subunit expression or urease enzyme activity in
      unsupplemented growth media. However, the nickel-induced increase in urease
      subunit expression and urease enzyme activity observed in wild-type H. pylori was
      absent in the H. pylori nikR mutant. A similar lack of nickel responsiveness was
      observed upon removal of a 19-bp palindromic sequence in the ureA promoter, as
      demonstrated by using a genomic ureA::lacZ reporter gene fusion. In conclusion,
      the H. pylori NikR protein and a 19-bp operator sequence in the ureA promoter are
      both essential for nickel-responsive induction of urease expression in H. pylori.

PMID- 12010972
TI  - The lbgAB gene cluster of Haemophilus ducreyi encodes a beta-1,4
      galactosyltransferase and an alpha-1,6-DD-heptosyltransferase involved in
      lipooligosaccharide biosynthesis.
AB  - All Haemophilus ducreyi strains examined contain a lipooligosaccharide (LOS)
      consisting of a single but variable branch oligosaccharide that emanates off the
      first heptose (Hep-I) of a conserved Hep(3)-phosphorylated 3-deoxy-D-manno
      octulosonic acid-lipid A core. In a previous report, identification of tandem
      genes, lbgA and lbgB, that are involved in LOS biosynthesis was described
      (Stevens et al., Infect. Immun. 65:651-660, 1997). In a separate study, the same
      gene cluster was identified and the lbgB (losB) gene was found to be required for
      transfer of the second sugar, D-glycero-D-manno-heptose (DD-Hep), of the major
      branch structure (Gibson et al., J. Bacteriol. 179:5062-5071, 1997). In this
      study, we identified the function of the neighboring upstream gene, lbgA, and
      found that it is necessary for addition of the third sugar in the dominant
      oligosaccharide branch, a galactose-linked beta1-->4, to the DD-Hep. LOS from an
      lbgA mutant and an lbgAB double mutant were isolated and were characterized by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, carbohydrate analysis,
      mass spectrometry, and nuclear magnetic resonance spectroscopy. The results
      showed that the mutant strains synthesize truncated LOS glycoforms that terminate
      after addition of the first glucose (lbgAB) or the disaccharide DD-Hepalpha1-
      >6Glcbeta1 (lbgA) that is attached to the heptose core. Both mutants show a
      significant reduction in the ability to adhere to human keratinocytes. Although
      minor differences were observed after two-dimensional gel electrophoresis of
      total proteins from the wild-type and mutant strains, the expression levels of
      the vast majority of proteins were unchanged, suggesting that the differences in
      adherence and invasion are due to differences in LOS. These studies add to the
      mounting evidence for a role of full-length LOS structures in the pathophysiology
      of H. ducreyi infection.

PMID- 12010973
TI  - Regulatory role of interleukin-10 in experimental group B streptococcal
      arthritis.
AB  - Intravenous inoculation of CD-1 mice with 10(7) CFU of type IV group B
      Streptococcus (GBS) results in a high incidence of diffuse septic arthritis,
      associated with high levels of systemic and local production of interleukin-1beta
      (IL-1beta) and IL-6. In this study, the role of the anti-inflammatory cytokine IL
      10 in the evolution of GBS systemic infection and arthritis was evaluated. IL-10
      production was evident in sera and joints of GBS-infected mice. Neutralization of
      endogenous IL-10 by administration of anti-IL-10 antibodies (1 mg/mouse) at the
      time of infection resulted in worsening of articular lesions and 60% mortality
      associated with early sustained production of IL-6, IL-1beta, and tumor necrosis
      factor alpha (TNF-alpha). The effect of IL-10 supplementation was assessed by
      administering IL-10 (100, 200, or 400 ng/mouse) once a day for 5 days, starting 1
      h after infection. Treatment with IL-10 had a beneficial effect on GBS arthritis,
      and there was a clear-cut dose dependence. The decrease in pathology was
      associated with a significant reduction in IL-6, IL-1beta, and TNF-alpha
      production. Histological findings showed limited periarticular inflammation and a
      few-cell influx in the articular cavity of IL-10-treated mice, confirming
      clinical observations. In conclusion, this study provides further information
      concerning the role of IL-10 in regulating the immune response and inflammation
      and calls attention to the potential therapeutic use of IL-10 in GBS arthritis.

PMID- 12010975
TI  - A glutamine transport gene, glnQ, is required for fibronectin adherence and
      virulence of group B streptococci.
AB  - Group B streptococci (GBS) are a leading cause of neonatal sepsis and meningitis.
      GBS adhere to fibronectin when it is attached to a solid phase. We isolated a
      Tn917 transposon mutant, COH1-GT1, which shows decreased adherence to
      fibronectin. COH1-GT1 also shows decreased adherence to and invasion of
      respiratory epithelial cells in vitro and decreased virulence in vivo. COH1-GT1
      contains a Tn917 insertion in a homolog of glnQ, a gene from Escherichia coli
      which is required for glutamine transport and codes for a cytoplasmic ATP-binding
      cassette protein. To confirm that the decreased fibronectin adherence of COH1-GT1
      was due to the mutation in glnQ, we constructed COH1-GT2, a strain with a
      nonpolar site-directed mutation in glnQ. COH1-GT2 showed decreased binding to
      fibronectin. We also demonstrated that complementation of glnQ in trans restored
      fibronectin adherence to COH1-GT1. COH1-GT1 shows decreased uptake of
      radiolabeled glutamine and is resistant to the toxic glutamine analog gamma-L
      glutamylhydrazide, demonstrating that the glnQ gene is required for glutamine
      transport in GBS. glnQ lacks a signal sequence and is a cytoplasmic protein in E.
      coli and thus is unlikely to act as a fibronectin adhesin. glnQ is transcribed in
      an operon with a putative glutamine permease gene, glnP, which has a novel
      predicted structure containing three distinct domains linked in a single gene.
      The first two domains are putative glutamine binding domains with homology to the
      E. coli periplasmic glutamine binding gene glnH. The third is a putative permease
      domain with homology to the E. coli glutamine permease gene glnP. RT-PCR analysis
      demonstrated that glnP and glnQ are contained within a single transcript.
      Transcription of scpB, encoding the only known fibronectin-binding adhesin of
      GBS, is unaffected. We speculate that glnQ may regulate expression of fibronectin
      adhesins by affecting cytoplasmic glutamine levels and that regulation may be
      posttranscriptional.

PMID- 12010974
TI  - Identification of novel adhesins from Group B streptococci by use of phage
      display reveals that C5a peptidase mediates fibronectin binding.
AB  - Group B streptococci (GBS) are a major cause of pneumonia, sepsis, and meningitis
      in newborns and infants. GBS initiate infection of the lung by colonizing mucosal
      surfaces of the respiratory tract; adherence of the bacteria to host cells is
      presumed to be the initial step in and prerequisite for successful colonization
      (G. S. Tamura, J. M. Kuypers, S. Smith, H. Raff, and C. E. Rubens, Infect. Immun.
      62:2450-2458, 1994). We have performed a genome-wide screen to identify novel
      genes of GBS that mediate adherence to fibronectin. A shotgun phage display
      library was constructed from chromosomal DNA of a serotype Ia GBS strain and
      affinity selected on immobilized fibronectin. DNA sequence analysis of different
      clones identified 19 genes with homology to known bacterial adhesin genes,
      virulence genes, genes involved in transport or metabolic processes, and genes
      with yet-unknown function. One of the isolated phagemid clones showed significant
      homology to the gene (scpB) for the GBS C5a peptidase, a surface-associated
      serine protease that specifically cleaves the complement component C5a, a
      chemotaxin for polymorphonuclear leukocytes. In this work we have demonstrated
      that affinity-purified recombinant ScpB and a peptide ScpB fragment (ScpB-PDF),
      similar to the peptide identified in the phagemid, bound fibronectin in a
      concentration-dependent manner. Adherence assays to fibronectin were performed,
      comparing an isogenic scpB mutant to the wild-type strain. Approximately 50% less
      binding was observed with the mutant than with the wild-type strain. The mutant
      phenotype could be fully restored by in trans complementation of the mutant with
      the cloned wild-type scpB gene, providing further evidence for the role of ScpB
      in fibronectin adherence. Our results suggest that C5a peptidase is a
      bifunctional protein, which enzymatically cleaves C5a and mediates adherence to
      fibronectin. Since binding of fibronectin has been implicated in attachment and
      invasion of eukaryotic cells by streptococci, our results may imply a second
      important role for this surface protein in the pathogenesis of GBS infections.

PMID- 12010976
TI  - Upper and lower respiratory tract infection by Streptococcus pneumoniae is
      affected by pneumolysin deficiency and differences in capsule type.
AB  - Pneumococci frequently colonize the upper respiratory tract, and these
      pneumococci are believed to act as a reservoir for infection of the lower
      respiratory tract and bacteremia. We investigated how the pneumococcal toxin
      pneumolysin affects the capacity of pneumococci to infect the upper and lower
      respiratory tract of the mouse. Wild-type Streptococcus pneumoniae serotype 2 and
      3 strains, a serotype 2 pneumolysin-deficient mutant, and a serotype 2 mutant
      with the pneumolysin gene reinserted were used to study differences in
      colonization and disease. In addition, we also examined a pneumococcal chimeric
      mutant (capsule type switched from serotype 2 to serotype 3) to gain further
      insight into the role that capsule plays in nasopharyngeal infection. Absence of
      pneumolysin was found to be associated with significantly lower numbers of
      pneumococci in the nasopharynx, trachea, and lungs. Differences in pneumococcal
      capsule type were found to have significant effects on pneumococcal infection of
      the nasopharynx, trachea, and lungs. However, it was the combination of capsule
      type and genetic background that was important, and the influence of this
      combination varied with the site of infection. For example, in the nasopharynx
      the wild-type serotype 3 strain and the capsule-switched mutant behaved
      similarly, whereas in the lungs the mutant that was switched to serotype 3
      survived less well than the wild-type serotype 3 strain. The combination of
      capsule type and genetic background also determined virulence. Thus, the wild
      type serotype 3 strain was virulent, whereas the capsule-switched mutant was
      avirulent.

PMID- 12010977
TI  - Expression and characterization of streptococcal rgp genes required for rhamnan
      synthesis in Escherichia coli.
AB  - Six genes (rgpA through rgpF) that were involved in assembling the rhamnose
      glucose polysaccharide (RGP) in Streptococcus mutans were previously identified
      (Y. Yamashita, Y. Tsukioka, K. Tomihisa, Y. Nakano, and T. Koga, J. Bacteriol.
      180:5803-5807, 1998). The group-specific antigens of Lancefield group A, C, and E
      streptococci and the polysaccharide antigen of Streptococcus sobrinus have the
      same rhamnan backbone as the RGP of S. mutans. Escherichia coli harboring plasmid
      pRGP1 containing all six rgp genes did not synthesize complete RGP. However, E.
      coli carrying a plasmid with all of the rgp genes except for rgpE synthesized the
      rhamnan backbone of RGP without glucose side chains, suggesting that in addition
      to rgpE, another gene is required for glucose side-chain formation. Synthesis of
      the rhamnan backbone in E. coli required the initiation of transfer of N
      acetylglucosamine to a lipid carrier and the expression of the rgpC and rgpD
      genes encoding the putative ABC transporter specific for RGP. The similarities in
      RGP synthesis between E. coli and S. mutans suggest common pathways for rhamnan
      synthesis. Therefore, we evaluated the rhamnosyl polymerization process in E.
      coli by high-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      of the lipooligosaccharide (LOS). An E. coli transformant harboring rgpA produced
      the LOS modified by the addition of a single rhamnose residue. Furthermore, the
      rgpA, rgpB, and rgpF genes of pRGP1 were independently mutated by an internal
      deletion, and the LOS chemotypes of their transformants were examined. The
      transformant with an rgpA deletion showed the same LOS profile as E. coli without
      a plasmid. The transformant with an rgpB deletion showed the same LOS profile as
      E. coli harboring rgpA alone. The transformant with an rgpF deletion showed the
      LOS band with the most retarded migration. On the basis of these results, we
      speculated that RgpA, RgpB, and RgpF, in that order, function in rhamnan
      polymerization.

PMID- 12010978
TI  - LsaA, an antigen involved in cell attachment and invasion, is expressed by
      Lawsonia intracellularis during infection in vitro and in vivo.
AB  - Lawsonia intracellularis has been identified recently as the etiological agent of
      proliferative enteropathies, which are characterized by intestinal epithelial
      hyperplasia and associated moderate immune responses. This disease complex has
      been reported in a broad range of animals, prevalently in pigs, and L.
      intracellularis has been linked with ulcerative colitis in humans. L.
      intracellularis is an obligate intracellular bacterium, and the pathogenic
      mechanisms used to cause disease are unknown. Using in vitro-grown organisms as a
      source of genomic DNA, we identified a Lawsonia gene which encodes a surface
      antigen, LsaA (for Lawsonia surface antigen), associated with attachment to and
      entry into cells. The deduced amino acid sequence of this protein showed some
      similarity to members of a novel protein family identified in a number of other
      bacterial pathogens but for which roles are not fully defined. Transcription of
      this gene was detected by reverse transcription-PCR in L. intracellularis grown
      in vitro in IEC18 cells and in bacteria present in ileal tissue from infected
      animals. Immunohistochemistry with specific monoclonal antibody and
      immunoblotting with sera from infected animals demonstrated that LsaA protein is
      synthesized by L. intracellularis during infection. Expression of this gene
      during infection in vitro and in vivo suggests that this surface antigen is
      involved during infection, and phenotypic analysis indicated a role during L.
      intracellularis attachment to and entry into intestinal epithelial cells

PMID- 12010979
TI  - Lipopolysaccharide-induced granule mobilization and priming of the neutrophil
      response to Helicobacter pylori peptide Hp(2-20), which activates formyl peptide
      receptor-like 1.
AB  - The cecropin-like bactericidal peptide Hp(2-20) from Helicobacter pylori induces
      activation of the NADPH oxidase in human neutrophils via formyl peptide receptor
      like 1 (FPRL1) (J. Bylund, T. Christophe, F. Boulay, T. Nystrom, A. Karlsson, and
      C. Dahlgren, Antimicrob. Agents Chemother. 45:1700-1704, 2001). Here we
      investigated the ability of bacterial lipopolysaccharide (LPS) to prime this
      response. Neutrophils treated with LPS for 30 min at 37 degrees C produced
      substantially more superoxide anion than control cells upon stimulation with Hp(2
      20). Hence, LPS primed the cells for subsequent stimulation through FPRL1. To
      study the molecular background of this priming phenomenon, we measured the
      degrees of granule mobilization and concomitant receptor upregulation to the cell
      surface in LPS-treated cells. Exposure of complement receptors 1 and 3 as well as
      the formyl peptide receptor (FPR) was markedly increased after LPS treatment.
      Since approximately 60% of the gelatinase granules were mobilized while the
      specific granules were retained, we hypothesized that the gelatinase granules
      were potential stores of FPRL1. The presence of FPRL1 mainly in the gelatinase
      granules was confirmed by Western blotting of subcellular fractions of resting
      neutrophils. These results suggest that the mechanism behind the LPS-induced
      priming of FPRL1-mediated responses lies at the level of granule (receptor)
      mobilization.

PMID- 12010980
TI  - Regulation of the overlapping pic/set locus in Shigella flexneri and
      enteroaggregative Escherichia coli.
AB  - Most strains of Shigella flexneri 2a and enteroaggregative Escherichia coli carry
      a highly conserved chromosomal locus which encodes a 109-kDa secreted mucinase
      (called Pic) and, on the opposite strand in overlapping fashion, an oligomeric
      enterotoxin called ShET1, encoded by the setA and setB genes. Here, we
      characterize the genetic regulation of these overlapping genes. Our data suggest
      that pic and the setBA loci are transcribed as complementary 4-kb mRNA species.
      The major pic promoter is maximally activated at 37 degrees C in exponential
      growth phase. Our data suggest that the setB gene is transcribed from a promoter
      which lies more than 1.5 kb upstream of the setB structural gene; setA may be
      transcribed via readthrough of the setB transcript and possibly by its own
      promoter. The long leader of the setB gene provides a strong silencing effect on
      setB transcription. The signals which provide relief from setB silencing are not
      clear, but significant induction is observed in a continuous anaerobic culture of
      human fecal bacteria, suggesting that some complex characteristics of the human
      intestine act to lift repression of setB expression. Our studies provide the
      first insights into the mechanisms affecting expression of this unusual virulence
      locus.

PMID- 12010981
TI  - Identification by mass spectrometry of CD8(+)-T-cell Mycobacterium tuberculosis
      epitopes within the Rv0341 gene product.
AB  - Identification of Mycobacterium tuberculosis proteins that can provide
      immunological protection against tuberculosis is essential for the development of
      a more effective vaccine. To identify new vaccine targets, we have used
      immunoaffinity chromatography to isolate class I HLA-A*0201-peptide complexes
      from M. tuberculosis-infected cells and sequenced the isolated peptides by mass
      spectrometry. From this material, we have identified three peptides derived from
      a single M. tuberculosis protein that is encoded by the M. tuberculosis Rv0341
      gene. Although no known protein encoded by the Rv0341 gene has been described, it
      is predicted to give rise to a 479-amino-acid protein with a molecular mass of
      43.9 kDa. The three peptides identified are all nested and were found to be
      antigenic, in that they were capable of inducing peptide-specific, CD8(+) T cells
      from healthy blood donors in vitro and capable of recognizing and lysing M.
      tuberculosis-infected dendritic cells. This methodology provides a powerful tool
      for the identification of M. tuberculosis proteins that can be evaluated as
      potential vaccine candidates.

PMID- 12010982
TI  - Insertional inactivation of Eap in Staphylococcus aureus strain Newman confers
      reduced staphylococcal binding to fibroblasts.
AB  - To initiate invasive infection, Staphylococcus aureus must adhere to host
      substrates, such as the extracellular matrix or eukaryotic cells, by virtue of
      different surface proteins (adhesins). Recently, we identified a 60-kDa cell
      secreted extracellular adherence protein (Eap) of S. aureus strain Newman with
      broad-spectrum binding characteristics (M. Palma, A. Haggar, and J. I. Flock, J.
      Bacteriol. 181:2840-2845, 1999), and we have molecularly confirmed Eap to be an
      analogue of the previously identified major histocompatibility complex class II
      analog protein (Map) (M. Hussain, K. Becker, C. von Eiff, G. Peter, and M.
      Herrmann, Clin. Diagn. Lab. Immunol. 8:1281-1286, 2001). Previous analyses of the
      Eap/Map function performed with purified protein did not allow dissection of its
      precise role in the complex situation of the staphylococcal whole cell presenting
      several secreted and wall-bound adhesins. Therefore, the role of Eap was
      investigated by constructing a stable eap::ermB deletion in strain Newman and by
      complementation of the mutant. Patterns of extracted cell surface proteins
      analyzed both by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by
      Western ligand assays with various adhesive matrix molecules clearly confirmed
      the absence of Eap in the mutant. However, binding and adhesion tests using whole
      staphylococcal cells demonstrated that both the parent and mutant strains bound
      equally well to fibronectin- and fibrinogen-coated surfaces, possibly due to
      their recognition by other staphylococcal adhesins. Furthermore, Eap mediated
      staphylococcal agglutination of both wild-type and mutant cells. In contrast, the
      mutant adhered to a significantly lesser extent to cultured fibroblasts (P <
      0.001) than did the wild type, while adherence was restorable upon
      complementation. Furthermore, adherence to both epithelial cells (P < 0.05) and
      fibroblasts (not significant) could be blocked with antibodies against Eap,
      whereas preimmune serum was not active. In conclusion, Eap may contribute to
      pathogenicity by promoting adhesion of whole staphylococcal cells to complex
      eukaryotic substrates.

PMID- 12010983
TI  - Antigen-presenting cell function during Plasmodium yoelii infection.
AB  - Antigen-presenting cells (APC) play a key role in orchestrating immune responses.
      T-cell proliferative responses are inhibited during the erythrocyte stages of
      malaria infection, and a number of studies have suggested that APC are
      responsible for this phenomenon. In the present studies we examine individual
      components of the T-cell-activating function of APC: expression of costimulatory
      and major histocompatibility complex (MHC) class II proteins, the ability to
      process and present antigen to T cells, and the ability to support cytokine
      production. We find that during the acute phases of Plasmodium yoelii erythrocyte
      stage infection, APC upregulate the expression of class II MHC and CD80, maintain
      expression of CD86, process and present antigen, and support gamma interferon
      production. However the CD11b(+) subpopulation produces a soluble factor or
      factors that specifically inhibit interleukin-2 (IL-2) production by responding
      CD4 T cells. This factor is distinct from prostaglandin E(2), NO, or transforming
      growth factor beta. The data suggest that IL-2 suppression observed during
      malaria infection is not due to functional defects of APC but is triggered by
      production of a factor(s) that actively suppresses production of IL-2 by T cells.

PMID- 12010984
TI  - Construction, characterization, and animal testing of WRSd1, a Shigella
      dysenteriae 1 vaccine.
AB  - WRSd1 is a Shigella dysenteriae 1 vaccine containing deletions of the virG(icsA)
      gene required for intercellular spreading and a 20-kb chromosomal region
      encompassing the Shiga toxin genes (stxAB). WRSd1 was constructed from S.
      dysenteriae 1 strain 1617 that was originally isolated during the 1968 to 1969
      epidemic of Shiga dysentery in Guatemala. The virG(icsA) deletion was constructed
      from a streptomycin-resistant (Str(r)) mutant of 1617 by a filter mating
      procedures using a virG(icsA) deletion derivative, pDeltavirG2. A colony that was
      invasive for HeLa cells and negative for the virG(icsA) gene by Southern blotting
      was grown anaerobically on plates containing chlorate for selection of resistant
      colonies that had lost the entire Shiga toxin gene. A virG(icsA) stxAB Str(r)
      mutant selected from the chlorate plates was designated WRSd1. This candidate
      vaccine was evaluated for safety, immunogenicity, and protective efficacy using
      the guinea pig keratoconjunctivitis model. WRSd1 was Sereny negative, and two
      applications of this strain to the cornea elicited a significant protective
      immune response against the S. dysenteriae 1 O antigen. Vaccination with WRSd1
      conferred protection against challenge with each of three virulent S. dysenteriae
      1 strains. Since a vaccine protecting against multiple Shigella species is
      required for most areas where Shigella is endemic, protection studies using a
      combination vaccine of Shigella sonnei vaccine strain WRSS1, Shigella flexneri 2a
      vaccine strain SC602, and WRSd1 were also performed. Guinea pigs vaccinated with
      a mixture of equal amounts of the three vaccine strains were protected against
      challenge with each of the homologous virulent strains. Unlike WRSS1 and SC602,
      however, the level of protection afforded by WRSd1 in a combination vaccine was
      lower than the protection elicited by a pure culture. A current Good
      Manufacturing Practice product of WRSd1 given intragastrically to rhesus monkeys
      proved safe and immunogenic.

PMID- 12010985
TI  - Induction of interleukin-12 and gamma interferon requires tumor necrosis factor
      alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus
      neoformans infection.
AB  - The development of T1-cell-mediated immunity is required to clear a pulmonary
      Cryptococcus neoformans infection. The objective of these studies was to
      determine the mechanism by which tumor necrosis factor alpha (TNF-alpha) augments
      the development of pulmonary T1 immunity to C. neoformans infection. TNF-alpha
      expression was detected in lavage sample cells at days 2, 3, and 7 following C.
      neoformans infection. The numbers of CFU in the lung were not different between
      control and anti-TNF-alpha-treated mice at any time point examined during the
      afferent phase of the response (days 0 to 7). However, neutralization of TNF
      alpha prevented the initiation of pulmonary clearance during the efferent phase
      of the response (day 14). Administration of anti-TNF-alpha monoclonal antibody
      (day 0) diminished the lung levels of TNF-alpha, interleukin-12 (IL-12), and
      gamma interferon (IFN-gamma) induced by C. neoformans at day 7 postinfection.
      Neutralization of TNF-alpha (day 0) also altered the IFN-gamma/IL-4 ratio in the
      lung-associated lymph nodes at day 7 following C. neoformans infection. Anti-TNF
      alpha-treated mice developed a pulmonary eosinophilia at day 14 postinfection.
      Consistent with the pulmonary eosinophilia, anti-TNF-alpha-treated mice exhibited
      elevated serum immunoglobulin E and inhibition of the anticryptococcal delayed
      type hypersensitivity response, indicating a shift toward a T2 response.
      Neutralization of IL-12 also prevented lung leukocyte production of IFN-gamma in
      response to the infection. These findings demonstrate that afferent-phase TNF
      alpha production is essential for the induction of IL-12 and IFN-gamma and
      neutralization of early TNF-alpha results in a T2 shift of the T1/T2 balance of
      antifungal immunity.

PMID- 12010986
TI  - Haemophilus ducreyi requires the flp gene cluster for microcolony formation in
      vitro.
AB  - Haemophilus ducreyi, the etiologic agent of chancroid, has been shown to form
      microcolonies when cultured in the presence of human foreskin fibroblasts. We
      identified a 15-gene cluster in H. ducreyi that encoded predicted protein
      products with significant homology to those encoded by the tad (for tight
      adhesion) locus in Actinobacillus actinomycetemcomitans that is involved in the
      production of fimbriae by this periodontal pathogen. The first three open reading
      frames in this H. ducreyi gene cluster encoded predicted proteins with a high
      degree of identity to the Flp (fimbria-like protein) encoded by the first open
      reading frame of the tad locus; this 15-gene cluster in H. ducreyi was designated
      flp. RT-PCR analysis indicated that the H. ducreyi flp gene cluster was likely to
      be a polycistronic operon. Mutations within the flp gene cluster resulted in an
      inability to form microcolonies in the presence of human foreskin fibroblasts. In
      addition, the same mutants were defective in the ability to attach to both
      plastic and human foreskin fibroblasts in vitro. An H. ducreyi mutant with an
      inactivated tadA gene exhibited a small decrease in virulence in the temperature
      dependent rabbit model for experimental chancroid, whereas another H. ducreyi
      mutant with inactivated flp-1 and flp-2 genes was as virulent as the wild-type
      parent strain. These results indicate that the flp gene cluster is essential for
      microcolony formation by H. ducreyi, whereas this phenotypic trait is not linked
      to the virulence potential of the pathogen, at least in this animal model of
      infection.

PMID- 12010987
TI  - Proteomic analysis of differentially expressed Chlamydia pneumoniae genes during
      persistent infection of HEp-2 cells.
AB  - Recent data have shown that the respiratory pathogen Chlamydia pneumoniae
      expresses an altered gene transcription profile during gamma interferon (IFN
      gamma)-induced persistent infection in vitro. In the present study, we examined,
      by proteomics, expression of C. pneumoniae proteins labeled intracellularly with
      [(35)S]methionine/cysteine under normal conditions or IFN-gamma-mediated
      persistence. The identity of differentially expressed proteins during persistent
      infection was determined by matching spots to those of proteins identified in C.
      pneumoniae elementary bodies by matrix-assisted laser desorption ionization mass
      spectrometry. Upon treatment with 50 U of IFN-gamma per ml, a marked upregulation
      of major outer membrane protein (MOMP), heat shock protein 60 (Hsp-60/GroEL), and
      proteins with functions in DNA replication (GyrA), transcription (RpoA, PnP),
      translation (Rrf), glycolysis (PgK, GlgP), and type III secretion (SctN) was
      observed at 24 h of infection. In contrast, no significant decreases in bacterial
      protein expression were found in C. pneumoniae-infected cells due to IFN-gamma
      treatment. Upregulation of C. pneumoniae proteins involved in diverse functions
      during persistent infection may allow the organism to resist the inhibitory
      effects of IFN-gamma while retaining basic functions. Future studies should
      examine the differential expression of chlamydial proteins during the
      developmental cycle under IFN-gamma pressure to obtain a finer representation of
      the gene products involved in establishing persistence.

PMID- 12010988
TI  - Malaria-induced acquisition of antibodies to Plasmodium falciparum variant
      surface antigens.
AB  - In areas of intense Plasmodium falciparum transmission, protective immunity is
      acquired during childhood in parallel with acquisition of agglutinating
      antibodies to parasite-encoded variant surface antigens (VSA) expressed on
      parasitized red blood cells. In a semi-immune child in such an area, clinical
      disease is caused mainly by parasites expressing VSA not recognized by
      preexisting VSA-specific antibodies in that child. Such malaria episodes are
      known to cause an increase in agglutinating antibodies specifically recognizing
      VSA expressed by the parasite isolate causing the illness, whereas antibody
      responses to other parasite isolates are relatively unaffected. However, the
      detailed kinetics of this VSA antibody acquisition are unknown and hence were the
      aim of this study. We show that P. falciparum malaria in Ghanaian children
      generally caused a rapid and sustained increase in variant-specific VSA antibody
      levels, while more transient and limited increases in levels of antibodies to VSA
      expressed by other parasite isolates were also seen. Plasma VSA antibody levels
      were positively correlated with the age of the healthy plasma donors but
      negatively correlated with the age of the parasite donors (the malaria patient).
      The data from this first detailed longitudinal study of acquisition of VSA
      antibodies support the hypothesis that naturally acquired protective immunity to
      P. falciparum malaria is mediated, at least in part, by VSA-specific antibodies.

PMID- 12010989
TI  - Pirfenidone blocks the in vitro and in vivo effects of staphylococcal enterotoxin
      B.
AB  - Pirfenidone [5-methyl-1-phenyl-2-(1H)-pyridone] down-regulates expression of
      cytokines and other mediators involved in the onset and development of pulmonary
      fibrosis. Pirfenidone also inhibits production of tumor necrosis factor alpha
      (TNF-alpha) from macrophages incubated with endotoxin and protects mice against
      endotoxin shock. Pirfenidone's ability to reduce cytokine expression in these
      disorders led us to investigate the drug's effect on another cytokine anomaly,
      superantigen-induced shock. BALB/c mice were exposed to staphylococcal
      enterotoxin B (SEB) either systemically or by aerosol and subsequently
      potentiated with a sublethal dose of lipopolysaccharide. In these experiments,
      pirfenidone given 2 to 4.25 h after SEB resulted in 80 to 100% survival versus
      only 0 to 10% survival among untreated control animals. Relative to serum
      cytokine levels from controls given toxin but no drug, there was a 35 to 80%
      decrease in TNF-alpha, interleukin 1, and other proinflammatory cytokines. In
      vitro experiments with human peripheral blood lymphocytes revealed that
      pirfenidone reduced SEB-induced cytokine levels 50 to 80% and inhibited 95% of
      SEB-induced T-cell proliferation. Overall, these studies demonstrated the
      potential utility of pirfenidone as a therapeutic against septic shock and the
      biological effects of SEB.

PMID- 12010990
TI  - Lipopolysaccharide down regulates both scavenger receptor B1 and ATP binding
      cassette transporter A1 in RAW cells.
AB  - Lipopolysaccharide (LPS) has recently been shown to facilitate macrophage foam
      cell formation and has been suggested to be a proatherogenic factor. The
      mechanism of LPS induced cholesterol accumulation, however, is unclear. In this
      report, using the macrophage-like RAW 264.7 cell line, we provide experimental
      evidence that LPS's proatherogenic effects may at least in part reflect altered
      cholesterol metabolism. Data presented demonstrate that in a dose-dependent
      manner, LPS is able to down regulate the mRNA expression of the two primary high
      density lipoprotein (HDL) receptors, scavenger receptor B1 (SR-B1) and ATP
      binding cassette A1 (ABCA1), with a 50% inhibitory concentration of less than 0.2
      ng/ml, as well as to decrease SR-B1 protein expression by 80%. We also found that
      LPS treatment resulted in a significant decrease (to 20% of the control level) of
      the specific (125)I-HDL binding as well as in 50% inhibition of the HDL-mediated
      cholesterol efflux compared to untreated cells. In addition, we compared the
      potencies of various modified LPS preparations and demonstrated that the
      phosphorylated lipid A portion of LPS, which is highly conserved among gram
      negative microorganisms, including Chlamydia, is primarily responsible for the
      effects of LPS on SR-B1 and ABCA1 expression. Inhibitors of NF-kappaB activation
      were observed to efficiently block the suppressive effect of LPS on SR-B1 and
      ABCA1, suggesting a mechanism involving NF-kappaB. These data indicate that the
      LPS effects on cholesterol metabolism may contribute to the proatherogenic
      properties of LPS.

PMID- 12010991
TI  - Identification of a quorum-sensing signal molecule in the facultative
      intracellular pathogen Brucella melitensis.
AB  - Brucella melitensis is a gram-negative alpha2-proteobacterium responsible for
      abortion in goats and for Malta fever in humans. This facultative intracellular
      pathogen invades and survives within both professional and nonprofessional
      phagocytes. A dichloromethane extract of spent culture supernatant from B.
      melitensis induces bioluminescence in an Escherichia coli acyl-homoserine lactone
      (acyl-HSL) biosensor strain based upon the activity of the LasR protein of
      Pseudomonas aeruginosa. HPLC fractionation of the extract, followed by mass
      spectrometry, identified the major active molecule as N-dodecanoylhomoserine
      lactone (C12-HSL). This is the first report of the production of an acyl-HSL by
      an intracellular pathogen. The addition of synthetic C12-HSL to an early log
      phase culture of either B. melitensis or Brucella suis 1330 reduces the
      transcription of the virB operon, which contains virulence genes known to be
      required for intracellular survival. This mimics events seen during the
      stationary phase of growth and suggests that quorum sensing may play a role in
      the control of virulence in Brucella.

PMID- 12010992
TI  - The LTR72 mutant of heat-labile enterotoxin of Escherichia coli enhances the
      ability of peptide antigens to elicit CD4(+) T cells and secrete gamma interferon
      after coapplication onto bare skin.
AB  - Application of antigens with an adjuvant onto bare skin is a needle-free and pain
      free immunization procedure that delivers antigens to the immunocompetent cells
      of the epidermis. We tested here the immunogenicity and adjuvanticity of two
      mutants of heat-labile enterotoxin (LT) of Escherichia coli, LTK63 and LTR72.
      Both mutants were shown to be immunogenic, inducing serum and mucosal antibody
      responses. The application of LTK63 and LTR72 to bare skin induced significant
      protection against intraperitoneal challenge with a lethal dose of LT. In
      addition, both LT mutants enhanced the capacity of peptides TT:830-843 and HA:307
      319 (representing T-helper epitopes from tetanus toxin and influenza virus
      hemagglutinin, respectively) to elicit antigen-specific CD4(+) T cells after
      coapplication onto bare skin. However, only mutant LTR72 was capable of
      stimulating the secretion of high levels of gamma interferon. These findings
      demonstrate that successful skin immunization protocols require the selection of
      the right adjuvant in order to induce the appropriate type of antigen-specific
      immune responses in a selective and reliable way. Moreover, the use of adjuvants
      such the LTK63 and LTR72 mutants, with no or low residual toxicity, holds a lot
      of promise for the future application of vaccines to the bare skin of humans.

PMID- 12010993
TI  - Alpha/beta interferon impairs the ability of human macrophages to control growth
      of Mycobacterium bovis BCG.
AB  - Administration of alpha/beta interferon (IFN-alpha/beta) to mice infected with
      Mycobacterium tuberculosis has been shown to increase mycobacterial growth.
      Because IFN-alpha/beta has direct pleiotropic effects on the differentiation and
      functional activities of macrophages, we evaluated the effect of IFN-alpha/beta
      on mycobacterial growth in human monocytes/macrophages in vitro. Monocytes
      cultured at optimal cell density could control the growth of M. bovis BCG, as
      assessed both by measurement of luciferase activity expressed by a mycobacterial
      reporter strain and by counting of CFU. In contrast, unrestrained mycobacterial
      growth was observed when monocytes were treated with alpha interferon (IFN-alpha)
      3 days prior to or concomitant with infection. This striking loss of
      mycobacteriostatic activity was observed with IFN-alpha and IFN-beta and was
      induced in both freshly isolated monocytes and culture-derived macrophages.
      Pretreatment of monocytes with IFN-alpha modified cellular morphology and reduced
      viability following culture, but neither was observed for culture-derived
      macrophages, indicating that the effects of IFN-alpha on mycobacteriostatic
      activity and cell differentiation and death could be dissociated. These results
      are compatible with the possibility that the secretion of IFN-alpha/beta could
      directly promote mycobacterial growth in patients harboring these organisms.

PMID- 12010994
TI  - Correlation of ESAT-6-specific gamma interferon production with pathology in
      cattle following Mycobacterium bovis BCG vaccination against experimental bovine
      tuberculosis.
AB  - Vaccine development and the understanding of the pathology of bovine tuberculosis
      in cattle would be greatly facilitated by the definition of immunological
      correlates of protection and/or pathology. To address these questions, cattle
      were vaccinated with Mycobacterium bovis bacillus Calmette-Guerin (BCG) and were
      then challenged with virulent M. bovis. Applying a semiquantitative pathology
      scoring system, we were able to demonstrate that BCG vaccination imparted
      significant protection by reducing the disease severity on average by 75%.
      Analysis of cellular immune responses following M. bovis challenge demonstrated
      that proliferative T-cell and gamma interferon (IFN-gamma) responses towards the
      M. bovis-specific antigen ESAT-6, whose gene is absent from BCG, were generally
      low in vaccinated animals but were high in all nonvaccinated calves. Importantly,
      the amount of ESAT-6-specific IFN-gamma measured by enzyme-linked immunosorbent
      assay after M. bovis challenge, but not the frequency of responding cells,
      correlated positively with the degree of pathology found 18 weeks after
      infection. Diagnostic reagents based on antigens not present in BCG, like ESAT-6
      and CFP-10, were still able to distinguish BCG-vaccinated, diseased animals from
      BCG-vaccinated animals without signs of disease. In summary, our results suggest
      that the determination of ESAT-6-specific IFN-gamma, while not a direct correlate
      of protection, constitutes nevertheless a useful prognostic immunological marker
      predicting both vaccine efficacy and disease severity.

PMID- 12010995
TI  - Peptidoglycan from Staphylococcus aureus induces tissue factor expression and
      procoagulant activity in human monocytes.
AB  - Staphylococcus aureus is one of the most significant pathogens in human sepsis
      and endocarditis. S. aureus can initiate blood coagulation, leading to the
      formation of microthrombi and multiorgan dysfunction in sepsis, whereas in
      endocarditis the bacterium induces fibrin clots on the inner surface of the
      heart, so-called endocardial vegetations. In the present study, we show that live
      and heat-killed S. aureus bacteria are potent inducers of procoagulant activity
      in human peripheral blood mononuclear cells. Furthermore, purified peptidoglycan,
      the main cell wall component of S. aureus, induced procoagulant activity in
      mononuclear cells in a concentration-dependent fashion. The procoagulant activity
      in these cells was dependent on expression of tissue factor, since antibodies to
      tissue factor inhibited the effect of peptidoglycan. In mononuclear cells
      stimulated with peptidoglycan, reverse transcription-PCR showed tissue factor
      gene expression, and the gene product was detected by enzyme-linked immunosorbent
      assay. Finally, flow cytometry identified tissue factor at the surface of CD14
      positive monocytes. Peptidoglycan is known to induce proinflammatory cytokine
      production in monocytes. The present investigation shows that peptidoglycan also
      activates the extrinsic pathway of coagulation by inducing the expression of
      tissue factor in these cells. This mechanism helps to explain the procoagulant
      activity, which plays such an important role in the pathogenicity of severe S.
      aureus infections.

PMID- 12010996
TI  - Differential regulation of the mitogen-activated protein kinases by pathogenic
      and nonpathogenic mycobacteria.
AB  - Mycobacteria are the etiologic agents of numerous diseases which account for
      significant morbidity and mortality in humans and other animal species. Many
      mycobacteria are intramacrophage pathogens and therefore the macrophage response
      to infection, which includes synthesis of cytokines such as tumor necrosis factor
      alpha (TNF-alpha) and production of nitric oxide, has important consequences for
      host immunity. However, very little is known about the macrophage cell signaling
      pathways initiated upon infection or how pathogenic mycobacteria may modulate the
      macrophage responses. Using primary murine bone marrow macrophages, we
      established that p38 and extracellular signal-regulated kinases 1 and 2 of the
      mitogen-activated protein kinase (MAPK) pathways are activated upon infection
      with different species of mycobacteria. However, we observed decreased MAPK
      activity over time in macrophages infected with pathogenic Mycobacterium avium
      strains relative to infections with nonpathogenic mycobacteria. Furthermore,
      macrophages infected with M. avium produced lower levels of TNF-alpha,
      interleukin 1beta, and inducible nitric oxide synthase 2 than macrophages
      infected with nonpathogenic species. Inhibitor studies indicate that the MAPKs
      are required for the Mycobacterium-mediated induction of these effector proteins.
      Our data indicate that MAPKs are activated in macrophages upon invasion by
      mycobacteria and that this activation is diminished in macrophages infected with
      pathogenic strains of M. avium, resulting in decreased production of important
      immune effector proteins. The decreased MAPK activation associated with M. avium
      infections suggests a novel point of immune intervention by this mycobacterial
      species.

PMID- 12010997
TI  - Characterization of the mouse beta defensin 1, Defb1, mutant mouse model.
AB  - Beta defensins are small cationic antimicrobial peptides present in the
      respiratory system which have been proposed to be dysfunctional in the
      environment of the cystic fibrosis lung. Defb1, a murine homologue to the human
      beta defensins, has also been found to be expressed in the respiratory system
      and, in order to examine the function of beta defensins in vivo, gene targeting
      was used to generate Defb1-deficient (Defb1(tm1Hgu)/Defb1(tm1Hgu) [Defb1(-/-)])
      mice. The Defb1 synthetic peptide was shown to have a salt-sensitive
      antimicrobial activity that was stronger against Staphylococcus aureus than
      against Escherichia coli or Pseudomonas aeruginosa. Defb1(-/-) mice were found,
      however, to be effective in the clearance of the cystic fibrosis relevant
      pathogen S. aureus from the airways after nebulization. Although no overt
      deleterious phenotype was evident in the Defb1(-/-) mice, the number of mutant
      mice found to harbor bacteria of the Staphylococcus species in the bladder was
      significantly higher (P = 0.008) than that of controls, suggesting a role for
      these peptides in resistance to urinary tract infection.

PMID- 12010998
TI  - Modulation of Borrelia burgdorferi stringent response and gene expression during
      extracellular growth with tick cells.
AB  - Borrelia burgdorferi N40 multiplied extracellularly when it was cocultured with
      tick cells in L15BS medium, a medium which by itself did not support B.
      burgdorferi N40 growth. Growth of B. burgdorferi N40 in the presence of tick
      cells was associated with decreased production of (p)ppGpp, the stringent
      response global regulator, a fourfold decrease in relA/spoT mRNA, an eightfold
      net decrease in bmpD mRNA, and a fourfold increase in rpsL-bmpD mRNA compared to
      growth of B. burgdorferi in BSK-H medium. As a result, the polycistronic rpsL
      bmpD mRNA level increased from 3 to 100% of the total bmpD message. These
      observations demonstrate that there are reciprocal interactions between B.
      burgdorferi and tick cells in vitro and indicate that the starvation-associated
      stringent response mediated by (p)ppGpp present in B. burgdorferi growing in BSK
      H medium is ameliorated in B. burgdorferi growing in coculture with tick cell
      lines. These results suggest that this system can provide a useful model for
      identifying genes controlling interactions of B. burgdorferi with tick cells in
      vitro when it is coupled with genetic methods to isolate and complement B.
      burgdorferi mutants.

PMID- 12010999
TI  - beta-Defensin 1 contributes to pulmonary innate immunity in mice.
AB  - Innate immunity serves as a first line defense in vertebrate organisms by
      providing an initial barrier to microorganisms and triggering antigen-specific
      responses. Antimicrobial peptides are thought to be effectors of innate immunity
      through their antibiotic activity and direct killing of microorganisms. Evidence
      to support this hypothesis in vertebrates is indirect, based on expression
      profiles and in vitro assays using purified peptides. Here we investigated the
      function of antimicrobial peptides in vivo using mice deficient in an
      antimicrobial peptide, mouse beta-defensin-1 (mBD-1). We find that loss of mBD-1
      results in delayed clearance of Haemophilus influenzae from lung. These data
      demonstrate directly that antimicrobial peptides of vertebrates provide an
      initial block to bacteria at epithelial surfaces.

PMID- 12011000
TI  - Helicobacter pylori does not require Lewis X or Lewis Y expression to colonize
      C3H/HeJ mice.
AB  - Helicobacter pylori strains frequently express Lewis X (Le(x)) and/or Le(y) on
      their cell surfaces as constituents of the O antigens of their lipopolysaccharide
      molecules. To assess the effect of Le(x) and Le(y) expression on the ability of
      H. pylori to colonize the mouse stomach and to adhere to epithelial cells,
      isogenic mutants were created in which fucT1 alone or fucT1 and fucT2, which
      encode the fucosyl transferases necessary for Le(x) and Le(y) expression, were
      deleted. C3H/HeJ mice were experimentally challenged with either wild-type 26695
      H. pylori or its isogenic mutants. All strains, whether passaged in the
      laboratory or recovered after mouse passage, colonized the mice well and without
      consistent differences. During colonization by the mutants, there was no
      reversion to wild type. Similarly, adherence to AGS and KatoIII cells was
      unaffected by the mutations. Together, these findings indicate that Le expression
      is not necessary for mouse gastric colonization or for H. pylori adherence to
      epithelial cells.

PMID- 12011001
TI  - Construction and phenotypic characterization of an auxotrophic mutant of
      Mycobacterium tuberculosis defective in L-arginine biosynthesis.
AB  - A mutant of Mycobacterium tuberculosis defective in the metabolism of L-arginine
      was constructed by allelic exchange mutagenesis. The argF mutant strain required
      exogenous L-arginine for growth in vitro, and in the presence of 0.96 mM L
      arginine, it achieved a growth rate and cell density in stationary phase
      comparable to those of the wild type. The mutant strain was also able to grow in
      the presence of high concentrations of argininosuccinate, but its auxotrophic
      phenotype could not be rescued by L-citrulline, suggesting that the
      DeltaargF::hyg mutation exerted a polar effect on the downstream argG gene but
      not on argH. The mutant strain displayed reduced virulence in immunodeficient
      SCID mice and was highly attenuated in immunocompetent DBA/2 mice, suggesting
      that L-arginine availability is restricted in vivo.

PMID- 12011002
TI  - Quorum-sensing Escherichia coli regulator A: a regulator of the LysR family
      involved in the regulation of the locus of enterocyte effacement pathogenicity
      island in enterohemorrhagic E. coli.
AB  - The locus of enterocyte effacement (LEE) is a chromosomal pathogenicity island
      that encodes the proteins involved in the formation of the attaching and effacing
      lesions by enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli
      (EPEC). The LEE comprises 41 open reading frames organized in five major operons,
      LEE1, LEE2, LEE3, tir (LEE5), and LEE4, which encode a type III secretion system,
      the intimin adhesin, the translocated intimin receptor (Tir), and other effector
      proteins. The first gene of LEE1 encodes the Ler regulator, which activates all
      the other genes within the LEE. We previously reported that the LEE genes were
      activated by quorum sensing through Ler (V. Sperandio, J. L. Mellies, W. Nguyen,
      S. Shin, and J. B. Kaper, Proc. Natl. Acad. Sci. USA 96:15196-15201, 1999). In
      this study we report that a putative regulator in the E. coli genome is itself
      activated by quorum sensing. This regulator is encoded by open reading frame
      b3243; belongs to the LysR family of regulators; is present in EHEC, EPEC, and E.
      coli K-12; and shares homology with the AphB and PtxR regulators of Vibrio
      cholerae and Pseudomonas aeruginosa, respectively. We confirmed the activation of
      b3243 by quorum sensing by using transcriptional fusions and renamed this
      regulator quorum-sensing E. coli regulator A (QseA). We observed that QseA
      activated transcription of ler and therefore of the other LEE genes. An EHEC qseA
      mutant had a striking reduction of type III secretion activity, which was
      complemented when qseA was provided in trans. Similar results were also observed
      with a qseA mutant of EPEC. The QseA regulator is part of the regulatory cascade
      that regulates EHEC and EPEC virulence genes by quorum sensing.

PMID- 12011003
TI  - Characterization of a novel type IV pilus locus encoded on the large plasmid of
      locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains
      that are virulent for humans.
AB  - The majority of Shiga-toxigenic Escherichia coli (STEC) strains isolated from
      humans with gastrointestinal disease carry large (approximately 90-kb) plasmids.
      We have been analyzing the megaplasmid (designated pO113) from an O113:H21 STEC
      strain (98NK2). This strain lacks the locus for enterocyte effacement (LEE) and
      yet was responsible for an outbreak of hemolytic uremic syndrome. In the present
      study, we demonstrate that pO113 carries a novel type IV pilus biosynthesis locus
      (pil) related to those of the IncI plasmids R721, R64, and ColIb9. The pO113 pil
      locus consists of 11 closely linked genes (pilL through pilV) with an additional
      separately transcribed upstream gene (pilI). It directs the expression of long
      thin pili on the 98NK2 surface and the hemagglutination of guinea pig
      erythrocytes. We also demonstrate that pO113 can be transferred by conjugation.
      However, the type IV pilus encoded by pO113 does not appear to be involved in the
      adherence of 98NK2 to HEp-2 or Hct-8 cells in vitro. Homologues of the pO113 pil
      locus were present in several other LEE-negative STEC strains but not in LEE
      positive STEC strains belonging to serogroup O26, O111, or O157.

PMID- 12011004
TI  - Purification, characterization, and immunogenicity of the refolded ectodomain of
      the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia
      coli.
AB  - The apical membrane antigen 1 (AMA1) has emerged as a promising vaccine candidate
      against malaria. Advanced evaluation of its protective efficacy in humans
      requires the production of highly purified and correctly folded protein. We
      describe here a process for the expression, fermentation, refolding, and
      purification of the recombinant ectodomain of AMA1 (amino acids 83(Gly) to
      531(Glu)) of Plasmodium falciparum (3D7) produced in Escherichia coli. A
      synthetic gene containing an E. coli codon bias was cloned into a modified pET32
      plasmid, and the recombinant protein was produced by using a redox-modified E.
      coli strain, Origami (DE3). A purification process was developed that included
      Sarkosyl extraction followed by affinity purification on a Ni-nitrilotriacetic
      acid column. The recombinant AMA1 was refolded in the presence of reduced and
      oxidized glutathione and further purified by using two ion-exchange
      chromatographic steps. The final product, designated AMA1/E, was homogeneous,
      monomeric, and >99% pure and had low endotoxin content and low host cell
      contamination. Analysis of AMA1/E showed that it had the predicted primary
      sequence, and tertiary structure analysis confirmed its compact disulfide-bonded
      nature. Rabbit antibodies made to the protein recognized the native parasite AMA1
      and inhibited the growth of the P. falciparum homologous 3D7 clone in an in vitro
      assay. Reduction-sensitive epitopes on AMA1/E were shown to be necessary for the
      production of inhibitory anti-AMA1 antibodies. AMA1/E was recognized by a
      conformation-dependent, growth-inhibitory monoclonal antibody, 4G2dc1. The
      process described here was successfully scaled up to produce AMA1/E protein under
      GMP conditions, and the product was found to induce highly inhibitory antibodies
      in rabbits.

PMID- 12011005
TI  - Oral vaccination with subunit vaccines protects animals against aerosol infection
      with Mycobacterium tuberculosis.
AB  - Immunity against Mycobacterium tuberculosis depends largely on activation of cell
      mediated responses, and gamma interferon has been shown to play a crucial role in
      this process in both humans and animal models. Since the lung is normally the
      organ in which infection is initiated and is the major site of pathology, immune
      responses in the lung play a significant role in restricting initial infection
      with M. tuberculosis. The aim of the present study was to stimulate efficient
      immunity in the lung by targeting the gut mucosa. Detoxified monophosphoryl lipid
      A (MPL) has been shown to be a relatively nontoxic adjuvant which efficiently
      promotes the induction of type 1 responses when it is given by the traditional
      subcutaneous route. We have therefore compared subcutaneous immunization of mice
      to oral immunization by using a model subunit vaccine carrying two immunodominant
      proteins from M. tuberculosis, in combination with MPL-based adjuvants. While
      less effective when used to prime a response, a heterologous priming and boosting
      vaccination strategy employing oral boosting induced significant systemic type 1
      responses which equaled and surpassed those attained by subcutaneous immunization
      protocols. Moreover, the increased immune responses observed correlated with the
      induction of substantial protection against subsequent aerosol infection with
      virulent M. tuberculosis at levels comparable to, or better than, those obtained
      by multiple subcutaneous vaccinations. These results demonstrate that booster
      vaccinations via mucosal surfaces, by combining efficient subunit vaccines with
      the potent adjuvant MPL, may be an effective method of addressing some of the
      shortcomings of current vaccination strategies.

PMID- 12011006
TI  - LACK-specific CD4(+) T cells that induce gamma interferon production in patients
      with localized cutaneous leishmaniasis during an early stage of infection.
AB  - The profile of cytokines induced by soluble leishmania antigen (SLA) and the
      Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a
      candidate vaccine against leishmaniasis, and the cellular source of the cytokines
      produced in response to these antigens were analyzed in patients infected with
      Leishmania guyanensis. Gamma interferon (IFN-gamma) and interleukin-10 (IL-10)
      were produced in response to LACK. Although LACK-specific CD4(+) cells producing
      IFN-gamma were isolated only during the early phase of infection (less than 30
      days following the onset of infection), cells producing IL-10 in response to LACK
      were detected in all patients. CD4(+) T cells producing IFN-gamma and IL-13 were
      produced in response to SLA in all patients. SLA- and LACK-specific T cells are
      effector memory cells, as they are CD45RA(-) CCR7(-) CD4(+) T cells. CD4(+) T
      cells producing IFN-gamma are CD62L(-), and CD4(+) T cells producing IL-10 are
      CD62L(+), indicating that these cells have different tissue-homing capacities.
      These findings show that SLA and LACK induce both type 1 (IFN-gamma) and type 2
      (IL-10 or IL-13) cell responses.

PMID- 12011007
TI  - Role of nitric oxide in host defense in murine salmonellosis as a function of its
      antibacterial and antiapoptotic activities.
AB  - Host defense functions of nitric oxide (NO) are known for many bacterial
      infections. In this study, we investigated the antimicrobial effect of NO in
      murine salmonellosis by using inducible NO synthase (iNOS)-deficient mice
      infected with an avirulent or virulent Salmonella enterica serovar Typhimurium
      strain. All iNOS-deficient mice died of severe septicemia within 6 days after
      intraperitoneal injection with an avirulent strain (LT2) to which wild-type mice
      were highly resistant; 50% lethal doses (LD(50)s) of the LT2 strain for iNOS
      deficient and wild-type mice were 30 CFU and 7 x 10(4) CFU, respectively. Lack of
      NO production in iNOS-deficient mice was verified directly by electron spin
      resonance spectroscopy. Bacterial yields in liver and blood were much higher in
      iNOS-deficient mice than in wild-type mice throughout the course of infection.
      Very small amounts of a virulent strain of serovar Typhimurium (a clinical
      isolate, strain Gifu 12142; LD(50), 50 CFU) given orally caused severe septicemia
      in iNOS-deficient animals; wild-type mice tolerated higher doses (LD(50), 6 x
      10(2) CFU). Histopathology of livers from infected iNOS-deficient mice revealed
      extensive damage, such as diffuse hepatocellular apoptosis and increased
      neutrophil infiltration, but livers from infected wild-type mice showed a limited
      number of microabscesses, consisting of polymorphonuclear cells and macrophages
      and low levels of apoptotic change. The LT2 strain was much more susceptible to
      the bactericidal effect of peroxynitrite than the Gifu strain, suggesting that
      peroxynitrite resistance may contribute to Salmonella pathogenicity. These
      results indicate that NO has significant host defense functions in Salmonella
      infections not only because of its direct antimicrobial effect but also via
      cytoprotective actions for infected host cells, possibly through its
      antiapoptotic effect.

PMID- 12011008
TI  - Bacteria induce osteoclastogenesis via an osteoblast-independent pathway.
AB  - Bacteria or their products may cause chronic inflammation and subsequent bone
      loss. This inflammation and bone loss may be associated with significant
      morbidity in chronic otitis media, periodontitis, endodontic lesions, and
      loosening of orthopedic implants caused by lipopolysaccharide (LPS)-contaminated
      implant particles. Currently, it is not clear how bacteria or endotoxin-induced
      bone resorption occurs and what cell types are involved. Here we report that
      Porphyromonas gingivalis, a periodontal pathogen, and Escherichia coli LPS induce
      osteoclastic cell formation from murine leukocytes in the absence of osteoblasts.
      In contrast, stimulation with parathyroid hormone had no effect. These
      multinucleated, tartrate-resistant acid phosphatase-positive cells were positive
      for receptor activator of NF-kappaB (RANK), the receptor for osteoprotegerin
      ligand (OPGL), also known as RANK ligand (RANKL). Blocking antibodies
      demonstrated that their formation was dependent upon expression of OPGL and, to a
      lesser extent, on tumor necrosis factor alpha. Mononuclear cells represented a
      significant source of OPGL production. In vivo, P. gingivalis injection
      stimulated OPGL expression in both mononuclear leukocytes and osteoblastic cells.
      Thus, these findings describe a pathway by which bacteria could enhance
      osteolysis independently of osteoblasts and suggest that the mix of cells that
      participate in inflammatory and physiologic bone resorption may be different.
      This may give insight into new targets of therapeutic intervention.

PMID- 12011009
TI  - Role of tumor necrosis factor alpha in Helicobacter pylori gastritis in tumor
      necrosis factor receptor 1-deficient mice.
AB  - Increased gastric production of interleukin 8 and tumor necrosis factor alpha
      (TNF-alpha) has been implicated in the pathogenesis of Helicobacter pylori
      associated gastroduodenal disease. In the present study we used a mouse model to
      demonstrate whether loss of the tumor necrosis factor receptor 1 (TNF-R1)
      function leads to differences in gastric inflammation or the systemic immune
      response in H. pylori infection. Six different clinical isolates of H. pylori
      (three cytotoxin-positive and three cytotoxin-negative strains) were adapted to
      C57BL/6 mice. TNF-R1-deficient (TNF-R1(-/-)) mice (n = 19) and isogenetic
      controls (n = 24) were infected and sacrificed after 4 weeks of infection.
      Inflammation of the stomach and the humoral immune response to H. pylori were
      evaluated by histological, immunohistochemical, and serological methods. There
      was no detectable difference in the grade or activity of gastritis in TNF-R1(-/-)
      mice when they were compared with wild-type mice, but the number of lymphoid
      aggregates was slightly reduced in the gastric mucosa of TNF-R1(-/-) mice.
      Interestingly, total immunoglobulin G (IgG), as well as IgG1, IgG2b, and IgG3, H.
      pylori-specific antibody titers were significantly higher in wild-type mice. As
      revealed by immunoblot analysis, the difference in reactivity against H. pylori
      antigens was not based on a failure to recognize single H. pylori antigens in TNF
      R1(-/-) mice. We therefore suggest that TNF-R1-mediated TNF-alpha signals might
      support a systemic humoral immune response against H. pylori and that the gastric
      inflammatory response to H. pylori infection seems to be independent of TNF-R1
      mediated signals.

PMID- 12011010
TI  - Uptake of Aspergillus fumigatus Conidia by phagocytic and nonphagocytic cells in
      vitro: quantitation using strains expressing green fluorescent protein.
AB  - Several pathogenic fungal organisms enter eukaryotic cells and manipulate the
      host cell environment to favor their own growth and survival. Aspergillus
      fumigatus is a saprophytic fungus that causes invasive lung disease in the
      immunocompromised host. To determine whether A. fumigatus could enter eukaryotic
      cells, we studied the uptake of two different GFP-expressing A. fumigatus strains
      into A549 lung epithelial cells, human umbilical vein endothelial (HUVE) cells,
      and J774 murine macrophages in vitro. A549 cells internalized 30% of the bound
      conidia whereas HUVE and J774 cells internalized 50 and 90%, respectively.
      Conidia within A549 cells remained viable for 6 h; however, 60 to 80% of conidia
      within J774 cells were killed after only 4 h. Live and heat-killed conidia were
      internalized to the same extent by A549 cells. After 6 h, almost none of the
      conidia inside A549 cells had germinated, whereas extracellular conidia had
      developed germ tubes. Internalization of conidia by A549 cells was a temperature
      dependent process and required rearrangement of the underlying host cell
      cytoskeleton; uptake was inhibited by 75% with 0.5 microM cytochalasin D and by
      65% with 5 microM colchicine. Fluorescent labeling of infected A549 cells with
      rhodamine phalloidin provided visible evidence of cytoskeletal alteration as many
      of the intracellular conidia were contained in actin-coated phagosomes. These
      data provide evidence that significant numbers of A. fumigatus conidia can be
      internalized by nonprofessional phagocytes in vitro and these cells may serve as
      reservoirs for immune cell evasion and dissemination throughout the host.

PMID- 12011011
TI  - Mice lacking monocyte chemoattractant protein 1 have enhanced susceptibility to
      an interstitial polymicrobial infection due to impaired monocyte recruitment.
AB  - Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that induces
      monocyte recruitment in a number of different pathologies, including infection.
      To investigate the role of MCP-1 in protecting a host from a chronic interstitial
      polymicrobial infection, dental pulps of MCP-1(-/-) mice and controls were
      inoculated with six different oral pathogens. In this model the recruitment of
      leukocytes and the impact of a genetic deletion on the susceptibility to
      infection can be accurately assessed by measuring the progression of soft tissue
      necrosis and osteolytic lesion formation. The absence of MCP-1 significantly
      impaired the recruitment of monocytes, which at later time points was threefold
      higher in the wild-type mice than in MCP-1(-/-) mice (P < 0.05). The consequence
      was significantly enhanced rates of soft tissue necrosis and bone resorption (P <
      0.05). We also determined that the MCP-1(-/-) mice were able to recruit
      polymorphonuclear leukocytes (PMNs) to a similar or greater extent as controls
      and to produce equivalent levels of Porphyromonas gingivalis-specific total
      immunoglobulin G (IgG) and IgG1. These results point to the importance of MCP-1
      expression and monocyte recruitment in antibacterial defense and demonstrate that
      antibacterial defense is not due to an indirect effect on PMN recruitment or
      modulation of the adaptive immune response.

PMID- 12011012
TI  - Molecular cloning of the fur gene from Actinobacillus actinomycetemcomitans.
AB  - In several bacterial species, iron availability in host tissues is coordinated
      with the expression of virulence determinants through the fur gene product.
      Initial experiments showed that a cloned Escherichia coli fur gene probe
      hybridized to Southern blots of Actinobacillus actinomycetemcomitans strain JP2
      (serotype b) chromosomal DNA. The A. actinomycetemcomitans fur gene was then
      cloned utilizing partial functional complementation of the fur mutant in E. coli
      strain H1780. Analysis of the cloned DNA sequence revealed a 438-bp open reading
      frame with a deduced 146-amino-acid sequence exhibiting 80% identity to
      Haemophilus influenzae Fur and 62% identity to E. coli Fur. The pUC Aafur gene
      probe (generated from JP2 serotype b) hybridized to representatives from all five
      A. actinomycetemcomitans serotypes as well as to two strains derived from
      monkeys, suggesting that fur is widely distributed in A. actinomycetemcomitans.
      Open reading frames having >70% identity with the E. coli and H. influenzae
      flavodoxin and gyrase A genes, respectively, were found. Expression of the A.
      actinomycetemcomitans fur gene product repressed fiu expression and siderophore
      production in E. coli. A gel shift assay demonstrated that the expressed A.
      actinomycetemcomitans Fur protein bound the bacterial fur consensus sequence.
      Further characterization of the fur gene product in A. actinomycetemcomitans may
      improve our understanding of its role in the pathogenesis of periodontal disease
      and may lead to specific therapeutic modalities.

PMID- 12011013
TI  - Expression of the biofilm-associated protein interferes with host protein
      receptors of Staphylococcus aureus and alters the infective process.
AB  - The adherence of Staphylococcus aureus to soluble proteins and extracellular
      matrix components of the host is one of the key steps in the pathogenesis of
      staphylococcal infections. S. aureus presents a family of adhesins called
      MSCRAMMs (microbial surface components recognizing adhesive matrix molecules)
      that specifically recognize host matrix components. We examined the influence of
      biofilm-associated protein (Bap) expression on S. aureus adherence to host
      proteins, epithelial cell cultures, and mammary gland sections and on
      colonization of the mammary gland in an in vivo infection model. Bap-positive
      strain V329 showed lower adherence to immobilized fibrinogen and fibronectin than
      isogenic Bap-deficient strain m556. Bacterial adherence to histological sections
      of mammary gland and bacterial internalization into 293 cells were significantly
      lower in the Bap-positive strains. In addition, the Bap-negative strain showed
      significantly higher colonization in vivo of sheep mammary glands than the Bap
      positive strain. Taken together, these results strongly suggest that the
      expression of the Bap protein interferes with functional properties of the
      MSCRAMM proteins, preventing initial bacterial attachment to host tissues and
      cellular internalization.

PMID- 12011014
TI  - Identification of a Neospora caninum microneme protein (NcMIC1) which interacts
      with sulfated host cell surface glycosaminoglycans.
AB  - The invasive stages of apicomplexan parasites enter their host cells through
      mechanisms which are largely conserved throughout the phylum. Host cell invasion
      is divided into two distinct events, namely, adhesion onto the host cell surface
      and the actual host cell entry process. The former is mediated largely through
      microneme proteins which are secreted at the onset of establishing contact with
      the host cell surface. Many of the microneme proteins identified so far contain
      adhesive domains. We here present the genomic and corresponding cDNA sequences
      coding for a 460-amino-acid (aa) microneme protein in Neospora caninum
      tachyzoites which, due to its homology to MIC1 in Toxoplasma gondii (TgMIC1), was
      named NcMIC1. The deduced NcMIC1 polypeptide sequence contains an N-terminal
      signal peptide of 20 aa followed by two tandemly internal repeats of 48 and 44
      aa, respectively. Integrated into each repeat is a CXXXCG sequence motif
      reminiscent of the thrombospondin-related family of adhesive proteins. The
      positioning of this motif is strictly conserved in TgMIC1 and NcMIC1. The C
      terminal part, comprised of 278 aa, was expressed in Escherichia coli, and
      antibodies affinity purified on recombinant NcMIC1 were used to confirm the
      localization within the micronemes by immunofluorescence and immunogold
      transmission electron microscopy of tachyzoites. Immunohistochemistry of mouse
      brains infected with tissue cysts showed that expression of this protein is
      reduced in the bradyzoite stage. Upon initiation of secretion by elevating the
      temperature to 37 degrees C, NcMIC1 is released into the medium supernatant.
      NcMIC1 binds to trypsinized, rounded Vero cells, as well as to Vero cell
      monolayers. Removal of glycosaminoglycans from the host cell surface and
      modulation of host cell surface glycosaminoglycan sulfation significantly reduces
      the binding of NcMIC1 to the host cell surface. Solid-phase binding assays
      employing defined glycosaminoglycans confirmed that NcMIC1 binds to sulfated
      glycosaminoglycans.

PMID- 12011015
TI  - Apoptosis in acute shigellosis is associated with increased production of Fas/Fas
      ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and
      interleukin-2.
AB  - Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from
      patients infected with Shigella dysenteriae type 1 was studied by the terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)
      technique and annexin V staining. Expression of proteins and cytokines
      participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas
      ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL
      18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute
      and convalescent stages of dysentery was quantified at the single-cell level by
      in situ immunostaining. Apoptotic cell death in the lamina propria was markedly
      up-regulated at the acute stage (P < 0.05), where an increased number of necrotic
      cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of
      T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent
      apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month
      after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL
      18, but not IL-2, at the acute stage than at the convalescent stage was observed.
      Increased expression of caspase-3 and IL-18 in tissues with severe inflammation
      compared to expression in those with mild inflammation was evident, implying a
      possible role in the perpetuation of inflammation. Significantly reduced cell
      death during convalescence was associated with a significant up-regulation of Bcl
      2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of
      infection. Thus, induction of apoptosis at the local site in the early phase of
      S. dysenteriae type 1 infection was associated with a significant up-regulation
      of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl
      2 and IL-2, which promote cell survival.

PMID- 12011016
TI  - Fate of Entamoeba histolytica during establishment of amoebic liver abscess
      analyzed by quantitative radioimaging and histology.
AB  - The protozoan parasite Entamoeba histolytica is the causative agent of
      amoebiasis, a human disease characterized by dysentery and liver abscess. The
      physiopathology of hepatic lesions can be satisfactorily reproduced in the
      hamster animal model by the administration of trophozoites through the portal
      vein route. Hamsters were infected with radioactively labeled amoebas for
      analysis of liver abscess establishment and progression. The radioimaging of
      material from parasite origin and quantification of the number inflammation foci,
      with or without amoebas, described here provides the first detailed assessment of
      trophozoite survival and death during liver infection by E. histolytica. The
      massive death of trophozoites observed in the first hours postinfection
      correlates with the presence of a majority of inflammatory foci without
      parasites. A critical point for success of infection is reached after 12 h when
      the lowest number of trophozoites is observed. The process then enters a
      commitment phase during which parasites multiply and the size of the infection
      foci increases fast. The liver shows extensive areas of dead hepatocytes that are
      surrounded by a peripheral layer of parasites facing inflammatory cells leading
      to acute inflammation. Our results show that the host response promotes massive
      parasite death but also suggest also that this is a major contributor to the
      establishment of inflammation during development of liver abscess.

PMID- 12011017
TI  - Phylogenetic analysis and prevalence of urosepsis strains of Escherichia coli
      bearing pathogenicity island-like domains.
AB  - We characterized 100 Escherichia coli urosepsis isolates from adult patients
      according to host compromise status by means of ribotyping, PCR phylogenetic
      grouping, and PCR detection of papG alleles and the virulence-related genes
      sfa/foc, fyuA, irp-2, aer, hly, cnf-1 and hra. We also tested these strains for
      copies of pap and hly and their direct physical linkage with other virulence
      genes in an attempt to look for pathogenicity islands (PAIs) described for the
      archetypal uropathogenic strains J96, CFT073, and 536. Most of the isolates
      belonged to E. coli phylogenetic groups B2 and D and bore papG allele II, aer,
      and fyuA/irp-2. papG allele II-bearing strains were more common in noncompromised
      patients, while papG allele-negative strains were significantly more frequent in
      compromised patients. Fifteen ribotypes were identified. The three archetypal
      strains harbored different ribotypes, and only one-third of our urosepsis strains
      were genetically related to one of the archetypal strains. Three and 18 strains
      harbored three and two copies of pap, respectively, and 5 strains harbored two
      copies of hly. papGIII was physically linked to hly, cnf-1, and hra (reported to
      be PAI II(J96)-like genetic elements) in 14% of the strains. The PAI II(J96)-like
      domain was inserted within pheR tRNA in 11 strains and near leuX tRNA in 3
      strains. Moreover, the colocalized genes cnf-1, hra, and hly were physically
      linked to papGII in four strains and to no pap gene in three strains. papGII and
      hly (reported to be PAI I(CFT073)-like genetic elements) were physically linked
      in 16 strains, pointing to a PAI I(CFT073)-like domain. Three strains contained
      both a PAI II(J96)-like domain and a PAI I(CFTO73)-like domain. Forty-two strains
      harbored papGII but not hly, in keeping with the presence of a PAI II(CFT073)
      like domain. Only one strain harbored a PAI I(536)-like domain (hly only), and
      none harbored a PAI I(J96)-like domain (papGI plus hly) or a PAI II(536)-like
      domain (papGIII plus hly). This study provides new data on the prevalence and
      variability of physical genetic linkage between pap and certain virulence
      associated genes that are consistent with their colocalization on archetypal
      PAIs.

PMID- 12011018
TI  - Dissemination of the phage-associated novel superantigen gene speL in recent
      invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan.
AB  - In Japan, more than 10% of streptococcal toxic shock-like syndrome (TSLS) cases
      have been caused by Streptococcus pyogenes M3/T3 isolates since the first
      reported TSLS case in 1992. Most M3/T3 isolates from TSLS or severe invasive
      infection cases during 1992 to 2001 and those from noninvasive cases during this
      period are indistinguishable in pulsed-field gel electropherograms. The longest
      fragments of these recent isolates were 300 kb in size, whereas those of isolates
      recovered during or before 1973 were 260 kb in size. These 260- and 300-kb
      fragments hybridized to each other, suggesting the acquisition of an about 40-kb
      fragment by the recent isolates. The whole part of the acquired fragment was
      cloned from the first Japanese TSLS isolate, NIH1, and its nucleotide sequence
      was determined. The 41,796-bp fragment is temperate phage phiNIH1.1, containing a
      new superantigen gene speL near its right attachment site. The C-terminal part of
      the deduced amino acid sequence of speL has 48 and 46% similarity with well
      characterized erythrogenic toxin SpeC and the most potent superantigen, SmeZ-2,
      respectively. None of 10 T3 isolates recovered during or before 1973 has speL,
      whereas all of 18 M3/T3 isolates recovered during or after 1992 and,
      surprisingly, Streptococcus equi subsp. equi ATCC 9527 do have this gene. Though
      plaques could not be obtained from phiNIH1.1, its DNA became detectable from the
      phage particle fraction upon mitomycin C induction, showing that this phage is
      not defective. A horizontal transfer of the phage carrying speL may explain the
      observed change in M3/T3 S. pyogenes isolates in Japan.

PMID- 12011019
TI  - Differences in innate immune responses (in vitro) to HeLa cells infected with
      nondisseminating serovar E and disseminating serovar L2 of Chlamydia trachomatis.
AB  - The inflammatory response associated with Chlamydia trachomatis genital
      infections is thought to be initiated by the release of proinflammatory cytokines
      from infected epithelial cells. This study focuses on the interactions between C.
      trachomatis-infected HeLa cells and immune cells involved in the early stages of
      infection, i.e., neutrophils and macrophages. First, we showed that the
      expression of interleukin-11 (IL-11), an anti-inflammatory cytokine mainly active
      on macrophages, was upregulated at the mRNA level in the genital tracts of
      infected mice. Second, incubation of differentiated THP-1 (dTHP-1) cells or
      monocyte-derived macrophages (MdM) with basal culture supernatants from C.
      trachomatis serovar E- or serovar L2-infected HeLa cells resulted in macrophage
      activation with a differential release of tumor necrosis factor alpha (TNF-alpha)
      and upregulation of indoleamine 2,3-deoxygenase (IDO) but not of Toll-like
      receptor 2 and 4 mRNA expression. Third, coculture of infected HeLa cells with
      dTHP-1 cells resulted in a reduction in chlamydial growth, which was more
      dramatic for serovar E than for L2 and which was partially reversed by the
      addition of anti-TNF-alpha antibodies for serovar E or exogenous tryptophan for
      both serovars but was not reversed by the addition of superoxide dismutase or
      anti-IL-8 or anti-IL-1beta antibodies. A gamma interferon-independent IDO mRNA
      upregulation was also detected in dTHP-1 cells from infected cocultures. Lastly,
      with a two-stage coculture system, we found that (i) supernatants from
      neutrophils added to the apical side of infected HeLa cell cultures were
      chlamydicidal and induced MdM to express antichlamydial activity and (ii)
      although polymorphonuclear leukocytes released more proinflammatory cytokines in
      response to serovar E- than in response to L2-infected cells, MdM were strongly
      activated by serovar L2 infection, indicating that the early inflammatory
      response generated with a nondisseminating or a disseminating strain is
      different.

PMID- 12011020
TI  - Enhanced delivery of exogenous peptides into the class I antigen processing and
      presentation pathway.
AB  - Current immunization strategies, using peptide or protein antigens, generally
      fail to elicit cytotoxic-T-lymphocyte responses, since these antigens are unable
      to access intracellular compartments where loading of major histocompatibility
      complex class I (MHC-I) molecules occurs. In an attempt to circumvent this, we
      investigated whether the GM1 receptor-binding B subunit of Escherichia coli heat
      labile toxin (EtxB) could be used to deliver class I epitopes. When a class I
      epitope was conjugated to EtxB, it was delivered into the MHC-I presentation
      pathway in a GM1-binding-dependent fashion and resulted in the appearance of MHC
      I-epitope complexes at the cell surface. Importantly, we show that the efficiency
      of EtxB-mediated epitope delivery could be strikingly enhanced by incorporating,
      adjacent to the class I epitope, a 10-amino-acid segment from the C terminus of
      the DNA polymerase (Pol) of herpes simplex virus. The replacement of this 10
      amino-acid segment by a heterologous sequence or the introduction of specific
      amino acid substitutions within this segment either abolished or markedly reduced
      the efficiency of class I epitope delivery. If the epitope was extended at its C
      terminus, EtxB-mediated delivery into the class I presentation pathway was found
      to be completely dependent on proteasome activity. Thus, by combining the GM1
      targeting function of EtxB with the 10-amino-acid Pol segment, highly efficient
      delivery of exogenous epitopes into the endogenous pathway of class I antigen
      processing and presentation can be achieved.

PMID- 12011021
TI  - Entamoeba histolytica lectins contain unique 6-Cys or 8-Cys chitin-binding
      domains.
AB  - The Jacob lectin, the most abundant glycoprotein in the cyst wall of Entamoeba
      invadens, contains five unique 6-Cys chitin-binding domains (CBDs). We identified
      Entamoeba histolytica and Entamoeba dispar genes encoding Jacob homologues, each
      of which contains two predicted 6-Cys CBDs. A unique 8-Cys CBD was found at the N
      termini of the E. histolytica chitinase and three other predicted lectins, called
      Jessie 1 to Jessie 3. The CBDs of four E. histolytica lectins (Jacob, chitinase,
      and Jessies 2 and 3) were expressed in secretory vesicles of transfected amebae
      and shown to bind to particulate chitin.

PMID- 12011022
TI  - Disruption of the Salmonella-containing vacuole leads to increased replication of
      Salmonella enterica serovar typhimurium in the cytosol of epithelial cells.
AB  - Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen
      that inhabits a vacuolar compartment, called the Salmonella-containing vacuole
      (SCV), in infected host cells. Maintenance of the SCV is accomplished by SifA,
      and mutants of this Salmonella pathogenicity island 2 type III effector replicate
      more efficiently in epithelial cells. Here we demonstrate that enhanced
      replication of sifA mutants occurs in the cytosol of these cells. Increased
      replication of wild-type bacteria was also observed in cells treated with
      wortmannin or expressing Rab5 Q79L or Rab7 N125I, all of which caused a loss of
      SCV integrity. Our findings demonstrate the requirement of the host cell
      endosomal system for maintenance of the SCV and that loss of this compartment
      allows increased replication of serovar Typhimurium in the cytosol of epithelial
      cells.

PMID- 12011024
TI  - Segmented filamentous bacteria interact with intraepithelial mononuclear cells.
AB  - Segmented filamentous bacteria (SFB) are found in multiple species and play an
      important role in the development of mucosal immunity. The mechanism by which the
      bacteria interact with the immune system has not been well defined. We provide
      morphologic evidence of direct interaction between SFB and intraepithelial
      mononuclear cells.

PMID- 12011023
TI  - Relationship of Yersinia pseudotuberculosis O antigens IA, IIA, and IVB: the IIA
      gene cluster was derived from that of IVB.
AB  - O antigen is part of the lipopolysaccharide present in the outer membrane of gram
      negative bacteria and is highly polymorphic. In this study, we obtained sequences
      of the O-antigen gene clusters for the Yersinia pseudotuberculosis antigens IA,
      IIA, and IVB. We propose that the IIA gene cluster was derived from the IVB
      cluster, one of the very few cases in which a parent gene cluster is identified,
      and that the IA gene cluster could be a hybrid of the IVB and IB gene clusters.
      All three O antigens contain 6-deoxy-D-mannoheptose, and we identified six genes
      for the biosynthetic pathway for the precursor of this sugar, GDP-6-deoxy-D
      mannoheptose.

PMID- 12011025
TI  - Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida
      albicans strains with selectable marker URA3 targeted to the ENO1 locus.
AB  - Previous evaluation of HWP1 in systemic candidiasis in CBA/J mice was done with
      Candida albicans strains with differing genetic locations of URA3 as a result of
      Ura-blaster mutagenesis. In this study, the presence of HWP1 and the location of
      URA3 contributed to the severity of murine systemic candidiasis in BALB/c mice.

PMID- 12011026
TI  - Role of interleukin-18 in host defense against disseminated Candida albicans
      infection.
AB  - In mice injected intravenously with Candida albicans, administration of anti
      interleukin-18 (IL-18) antibodies increased the yeast load in the kidneys. There
      was no effect on the organ load with Candida when gamma interferon (IFN-gamma)
      deficient mice were treated with anti-IL-18 antibodies, suggesting that the
      protective effect of IL-18 is mediated through endogenous IFN-gamma.

PMID- 12011027
TI  - Protection of mice against Coccidioides immitis intranasal infection by
      vaccination with recombinant antigen 2/PRA.
AB  - Subcutaneous vaccination with recombinant antigen 2/PRA (rAg2/PRA) protected
      BALB/c mice against intranasal infection with Coccidioides immitis.
      Subcutaneously vaccinated C57BL/6 mice and intranasally vaccinated BALB/c mice
      were protected against larger numbers of infecting spores. Weight loss correlated
      with lethality, but histologic appearance did not. These studies support rAg2/PRA
      vaccination to prevent coccidioidomycosis.

PMID- 12011028
TI  - Characterization of the spv locus in Salmonella enterica serovar Arizona.
AB  - Salmonella enterica serovar Arizona (S. enterica subspecies IIIa) is a common
      Salmonella isolate from reptiles and can cause serious systemic disease in
      humans. The spv virulence locus, found on large plasmids in Salmonella subspecies
      I serovars associated with severe infections, was confirmed to be located on the
      chromosome of serovar Arizona. Sequence analysis revealed that the serovar
      Arizona spv locus contains homologues of spvRABC but lacks the spvD gene and
      contains a frameshift in spvA, resulting in a different C terminus. The SpvR
      protein functions as a transcriptional activator for the spvA promoter, and SpvB
      and SpvC are highly conserved. The analysis supports the proposal that the
      chromosomal spv sequence more closely corresponds to the ancestral locus acquired
      during evolution of S. enterica, with plasmid acquisition of spv genes in the
      subspecies I strains involving addition of spvD and polymorphisms in spvA.

PMID- 12011029
TI  - Role of gamma interferon in Helicobacter pylori induction of inflammatory
      mediators during murine infection.
AB  - Gamma interferon (IFN-gamma) has been proposed to play an important role in
      Helicobacter-related gastritis. Using the IFN-gamma gene knockout (IFN-gamma(-/
      )) mouse model and a murine gastric epithelial cell line, GSM06, we demonstrated
      that Helicobacter pylori maximally induced macrophage inflammatory protein-2 (MIP
      2) and inducible nitric oxide synthase (iNOS) mRNA only in wild-type mice. MIP-2
      and iNOS mRNA were also induced by H. pylori in GSM06 cells. Induction of
      cyclooxygenase 2 mRNA through IFN-gamma was demonstrated in GSM06 cells. These
      data indicate that IFN-gamma mediates the induction of MIP-2 and iNOS mRNA
      expression by H. pylori in mice.

PMID- 12011030
TI  - DNA microarray assessment of putative Borrelia burgdorferi lipoprotein genes.
AB  - A DNA microarray containing fragments of 137 Borrelia burgdorferi B31 putative
      lipoprotein genes was used to examine Lyme disease spirochetes. DNA from B.
      burgdorferi sensu stricto B31, 297, and N40; Borrelia garinii IP90; and Borrelia
      afzelii P/Gau was fluorescently labeled and hybridized to the microarray,
      demonstrating the degree to which the individual putative lipoprotein genes were
      conserved among the genospecies. These data show that a DNA microarray can
      globally examine the genes encoding B. burgdorferi lipoproteins.

PMID- 12011036
TI  - Copper ion-sensing transcription factor Mac1p post-translationally controls the
      degradation of its target gene product Ctr1p.
AB  - Copper ion uptake must be regulated to avoid both deficiency and excess because
      its essential yet toxic biological nature depends on the concentration. Yeast
      copper uptake is controlled at both the transcriptional and post-translational
      levels. The transcription of CTR1 and CTR3, encoding high affinity copper ion
      transporters, is regulated by the copper ion-sensing transcription factor Mac1p
      through the cis-acting copper ion-responsive elements in CTR1 and CTR3 promoters.
      Ctr1p is known to undergo degradation in cells exposed to high copper levels. We
      report that Mac1p is also required for copper-dependent Ctr1p degradation. Both
      mutations within a conserved copper ion binding motif, the "Cu-fist" in the Mac1p
      DNA-binding domain, and within a metal ion binding motif, REP-III located in the
      cytosolic domain of Ctr1p, cause defects in Ctr1p turnover. Furthermore, we show
      that the Mac1p limits intracellular copper accumulation likely by controlling
      Ctr1p degradation. The findings have uncovered an unprecedented mechanism by
      which a transcription factor not only regulates its target gene transcription but
      also controls the degradation of its target gene product.

PMID- 12011031
TI  - Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine
      proteinases from Porphyromonas gingivalis leading to down-regulation of
      lipopolysaccharide-induced interleukin-8 production.
AB  - Arginine-specific cysteine proteinases (gingipains-R) from periodontopathic
      Porphyromonas gingivalis cleaved CD14, a bacterial pattern recognition receptor,
      on human gingival fibroblasts (HGF). Consequently, gingipains-R reduced
      lipopolysaccharide-induced interleukin-8 production by HGF, indicating that
      gingipains-R inhibited CD14-dependent HGF activation and are involved in immune
      evasion by the bacterium in periodontal tissues.

PMID- 12011037
TI  - Hansenula polymorpha Pex3p is a peripheral component of the peroxisomal membrane.
AB  - Hansenula polymorpha Pex3p plays an essential role in the biogenesis and
      maintenance of the peroxisomal membrane. In the initial report, bakers' yeast
      Pex3p was suggested to represent an integral component of the peroxisomal
      membrane, containing one membrane-spanning region that exposes the N terminus of
      the protein into the organellar matrix. Biochemically, HpPex3p behaved like an
      integral membrane protein as it was resistant toward high salt and carbonate
      treatment. However, urea fully removed Pex3p from the membrane under conditions
      in which the integral membrane protein Pex10p was resistant to this treatment.
      Additional experiments, including protease protection assays and pre-embedding
      labeling experiments on purified organellar fractions from cells that produced
      Pex3ps carrying Myc epitopes at various selected locations in the protein,
      revealed that invariably all Myc tags were accessible for externally added
      proteases and antibodies, independent of the presence of detergents. Also,
      overproduction of Pex3p failed to demonstrate the typical integral membrane
      protein structures in fracture faces of freeze-fractured peroxisomes. Taken
      together, our data suggest that HpPex3p does not span the peroxisomal membrane
      but instead is tightly associated to the cytosolic face of the organelle where it
      may be present in focal protein clusters.

PMID- 12011038
TI  - A close association of the ganglioside-specific sialidase Neu3 with caveolin in
      membrane microdomains.
AB  - The ganglioside-specific sialidase Neu3 has been suggested to play essential
      roles in regulation of cell surface functions because of its major localization
      in the plasma membrane and strict substrate preference for gangliosides involved
      in signal transduction. Here we show that human Neu3 sialidase is enriched in
      caveolae microdomains and closely associates with caveolin like other caveolin
      binding signaling molecules. Using HeLa cells and Neu3-transfected COS-1 cells,
      endogenous and exogenous Neu3 was found to co-concentrate caveolin-1 in low
      density Triton X-100-insoluble membrane fractions on sucrose density gradients of
      the respective cell extracts, as assessed by enzyme activity assays and
      immunoblotting with a monoclonal antibody to human Neu3. The presence of a
      putative caveolin-binding motif within Neu3 prompted us to determine whether Neu3
      binds to caveolin-1. In transfectants expressing a polyhistidine-tagged form of
      Neu3, caveolin-1 co-eluted with Neu3 on affinity column chromatography. A
      mutation with a single amino acid change in the caveolin-binding motif led to
      inhibition of recruitment of the sialidase to the microdomain, accompanied by
      reduction of the enzyme activity. Neu3 also failed to associate with caveolin
      enriched microdomains by cholesterol depletion with beta-cyclodextrin (with
      concomitant decrease of the sialidase activity), whereas Neu3 was activated by
      increased caveolin-1 expression. The tight association of Neu3 with caveolin-1
      was supported further by co-immunoprecipitation of Neu3 by anti-caveolin-1
      antibody. These results strongly suggest that Neu3 functions as a caveolin
      related signaling molecule within caveolin-rich microdomains.

PMID- 12011039
TI  - Regulation of cellular oncosis by uncoupling protein 2.
AB  - Cell death can proceed through at least two distinct pathways. Apoptosis is an
      energy-dependent process characterized morphologically by cell shrinkage, whereas
      oncosis is a form of cell death induced by energy depletion and initially
      characterized by cell swelling. We demonstrate in HeLa cells but not in normal
      diploid fibroblasts that modest increases in the expression level of uncoupling
      protein 2 (UCP-2) leads to a rapid and dramatic fall in mitochondrial membrane
      potential and to a reduction of mitochondrial NADH and intracellular ATP. In HeLa
      cells, increased UCP-2 expression leads to a form of cell death that is not
      inhibited by the anti-apoptotic gene product Bcl-2 and that morphologically
      resembles cellular oncosis. We further describe the creation of a dominant
      interfering mutant of UCP-2 whose expression increases resting mitochondrial
      membrane potential and selectively increases the resistance to cell death
      following oncotic but not apoptotic stimuli. These results suggest that distinct
      genetic programs may regulate the cellular response to either apoptotic or
      oncotic stimuli.

PMID- 12011040
TI  - The novel role of the C-terminal region of SHP-2. Involvement of Gab1 and SHP-2
      phosphatase activity in Elk-1 activation.
AB  - SHP-2, a nontransmembrane-type protein-tyrosine phosphatase that contains two Src
      homology 2 (SH2) domains, is thought to participate in growth factor signal
      transduction pathways via SH2 domain interactions. To determine the role of each
      region of SHP-2 in platelet-derived growth factor signaling assayed by Elk-1
      activation, we generated six deletion mutants of SHP-2. The large SH2 domain
      deletion SHP-2 mutant composed of amino acids 198-593 (SHP-2-(198-593)), but not
      the smaller SHP-2-(399-593), showed significantly higher SHP-2 phosphatase
      activity in vitro. In contrast, SHP-2-(198-593) mutant inhibited wild type SHP-2
      phosphatase activity, whereas SHP-2-(399-593) mutant increased activity. To
      understand these functional changes, we focused on the docking protein Gab1 that
      assembles signaling complexes. Pull-down experiments with Gab1 suggested that the
      C-terminal region of SHP-2 as well as the SH2 domains (N-terminal region)
      associated with Gab1, but the SHP-2-(198-593) mutant did not associate with Gab1.
      SHP-2-(1-202) or SHP-2-(198-593) inhibited platelet-derived growth factorinduced
      Elk-1 activation, but SHP-2-(399-593) increased Elk-1 activation. Co-expression
      of SHP-2-(1-202) with SHP-2-(399-593) inhibited SHP-2-(399-593)/Gab1 interaction,
      and the SHP-2-(399-593) mutant induced SHP-2 phosphatase and Elk-1 activation,
      supporting the autoinhibitory effect of SH2 domains on the C-terminal region of
      SHP-2. These data suggest that both SHP-2/Gab1 interaction in the C-terminal
      region of SHP-2 and increased SHP-2 phosphatase activity are important for Elk-1
      activation. Furthermore, we identified a novel sequence for SHP-2/Gab1
      interactions in the C-terminal region of SHP-2.

PMID- 12011041
TI  - Maturation of cytosolic iron-sulfur proteins requires glutathione.
AB  - Glutathione is the major protective agent against oxidative stress in
      Saccharomyces cerevisiae. Deletion of the GSH1 gene (strain Deltagsh1) encoding
      the enzyme that catalyzes the first step of glutathione biosynthesis leads to
      growth arrest, which can be relieved by either glutathione or reducing agents
      such as dithiothreitol. Because defects in the biosynthesis of cellular iron
      sulfur (Fe/S) proteins are associated with increases in glutathione levels, we
      examined the consequences of glutathione depletion on this essential process. No
      significant defects were detected in the amounts, activities, and maturation of
      mitochondrial Fe/S proteins in glutathione-depleted Deltagsh1 cells. On the
      contrary, the maturation of extra-mitochondrial Fe/S proteins was decreased
      substantially. The defect was rectified neither by addition of dithiothreitol nor
      under anaerobic conditions excluding oxidative damage of Fe/S clusters. A double
      mutant in GSH1 and ATM1 encoding a mitochondrial ATP binding cassette (ABC)
      transporter involved in cytosolic Fe/S protein maturation is nonviable even in
      the presence of dithiothreitol. Similar to atm1 and other mutants defective in
      cytosolic Fe/S protein maturation, mitochondria from glutathione-depleted
      Deltagsh1 cells accumulated high amounts of iron. Together, our data demonstrate
      that glutathione, in addition to its protective role against oxidative damage,
      performs a novel and specific function in the maturation of cytosolic Fe/S
      proteins.

PMID- 12011042
TI  - Unexpected crucial role of residue 272 in substrate specificity of fibroblast
      collagenase.
AB  - Degradation of type I collagen by collagenases is an important part of
      extracellular remodeling. To understand the role of the hinge region of
      fibroblast collagenase in its collagenolytic activity, we individually
      substituted the 10 conserved amino acid residues at positions 264, 266, 268, 296,
      272, 277, 284, 289, 307, and 313 in this region of the enzyme by their
      corresponding residues in MMP-3, a noncollagenolytic matrix metalloproteinase.
      The general proteolytic and triple helicase activities of all of the enzymes were
      determined, and their abilities to bind to type I collagen were assessed. Among
      the mutants, only G272D mutant enzyme exhibited a significant change in type I
      collagenolysis. The alteration of the Gly(272) to Asp reduced the collagenolytic
      activity of the enzyme to 13% without affecting its general proteolytic activity,
      substrate specificity, or the collagen binding ability. The catalytic efficiency
      of the G272D mutant for the triple helical peptide substrate [C(6)-(GP-
      Hyp)(4)GPL(Mca)GPQGLRGQL(DPN)GVR(GP-HYP)(4)-NH(2)](3) and the peptide substrate
      Mca-PLGL(Dpa)AR-NH(2) and its dissociation constant for the triple helical
      collagen were similar to that of the wild type enzyme, indicating that the
      presence of this residue in fibroblast collagenase is particularly important for
      the efficient cleavage of type I collagen. Gly(272) is evidently responsible for
      the hinge-bending motion that is essential for allowing the COOH-terminal domain
      to present the collagen to the active site.

PMID- 12011043
TI  - The troponin tail domain promotes a conformational state of the thin filament
      that suppresses myosin activity.
AB  - In cardiac and skeletal muscles tropomyosin binds to the actin outer domain in
      the absence of Ca(2+), and in this position tropomyosin inhibits muscle
      contraction by interfering sterically with myosin-actin binding. The globular
      domain of troponin is believed to produce this B-state of the thin filament
      (Lehman, W., Hatch, V., Korman, V. L., Rosol, M., Thomas, L. T., Maytum, R.,
      Geeves, M. A., Van Eyk, J. E., Tobacman, L. S., and Craig, R. (2000) J. Mol.
      Biol. 302, 593-606) via troponin I-actin interactions that constrain the
      tropomyosin. The present study shows that the B-state can be promoted
      independently by the elongated tail region of troponin (the NH(2) terminus (TnT
      (1-153)) of cardiac troponin T). In the absence of the troponin globular domain,
      TnT-(1-153) markedly inhibited both myosin S1-actin-tropomyosin MgATPase activity
      and (at low S1 concentrations) myosin S1-ADP binding to the thin filament.
      Similarly, TnT-(1-153) increased the concentration of heavy meromyosin required
      to support in vitro sliding of thin filaments. Electron microscopy and three
      dimensional reconstruction of thin filaments containing TnT-(1-153) and either
      cardiac or skeletal muscle tropomyosin showed that tropomyosin was in the B-state
      in the complete absence of troponin I. All of these results indicate that
      portions of the troponin tail domain, and not only troponin I, contribute to the
      positioning of tropomyosin on the actin outer domain, thereby inhibiting muscle
      contraction in the absence of Ca(2+).

PMID- 12011044
TI  - Conformational remodeling of proteasomal substrates by PA700, the 19 S regulatory
      complex of the 26 S proteasome.
AB  - PA700, the 19 S regulatory complex of the 26 S proteasome, plays a central role
      in the recognition and efficient degradation of misfolded proteins. PA700
      promotes degradation by recruiting proteasomal substrates utilizing polyubiquitin
      chains and chaperone-like binding activities and by opening the access to the
      core of the 20 S proteasome to promote degradation. Here we provide evidence that
      PA700 in addition to binding misfolded protein substrates also acts to remodel
      their conformation prior to proteolysis. Scrambled RNase A (scRNase A), a
      misfolded protein, only slowly refolds spontaneously into an active form because
      of the rate-limiting unfolding of misfolded disulfide isomers. Notably, PA700
      accelerates the rate of reactivation of scRNase A, consistent with its ability to
      increase the exposure of these disulfide bonds to the solvent. In this regard,
      PA700 also exposes otherwise buried sites to digestion by exogenous chymotrypsin
      in a polyubiquitinated enzymatically active substrate, pentaubiquitinated
      dihydrofolate reductase, Ub(5)DHFR. The dihydrofolate reductase ligand
      methotrexate counters the ability of PA700 to promote digestion by chymotrypsin.
      Together, these results indicate that in addition to increasing substrate
      affinity and opening the access channel to the catalytic sites, PA700 activates
      proteasomal degradation by remodeling the conformation of protein substrates.

PMID- 12011045
TI  - Specificity of Rho insert-mediated activation of phospholipase D1.
AB  - Members of the Rho subfamily of GTP-binding proteins regulate phospholipase D1
      (PLD1) activity and signaling. In previous work, we demonstrated that binding of
      the Rho family member Cdc42 to PLD1 and the subsequent stimulation of its
      enzymatic activity are distinct events. Deletion of the insert helix from Cdc42
      does not interfere with its switch I-mediated, GTP-dependent binding to PLD1 but
      inhibits Cdc42-stimulated PLD1 activity. To understand the mechanism of the
      insert-mediated activation of PLD1 by Cdc42 and to develop reagents to study
      Cdc42-activated PLD1 in cellular signaling events, we have undertaken a
      mutational analysis of the Rho insert region of Cdc42 and examined the
      specificity of the insert helix requirement in the other Rho family members, RhoA
      and Rac1. Here, we identify a critical residue, serine 124, in the Cdc42 insert
      helix central to its activation mechanism. Further, we examine this activation
      mechanism with respect to other members of the Rho family and demonstrate that
      each Rho protein activates PLD by distinct mechanisms, potentially allowing for
      unique signaling outcomes in the cell.

PMID- 12011046
TI  - Insulin-like growth factor I prevents mannitol-induced degradation of focal
      adhesion kinase and Akt.
AB  - In our laboratory, we are interested in hyperosmolarity-induced apoptosis in
      neuronal cells. We have shown that high concentrations of glucose or mannitol
      induce apoptotic cell death in dorsal root ganglia in culture and in SH-SY5Y and
      SH-EP human neuroblastoma cells. Focal adhesion kinase (FAK) is a cytoplasmic
      tyrosine kinase that has a critical role for transmitting integrin-mediated
      signals. In this study, we report that hyperosmolar treatment mediates FAK
      dephosphorylation and cleavage, which is prevented by insulin-like growth factor
      I (IGF-I) treatment. Mannitol treatment of SH-EP cells transfected with vector
      (SH-EP/pSFFV) results in concentration- and time-dependent dephosphorylation and
      degradation of FAK. Dephosphorylation and degradation of FAK are tightly
      correlated with apoptotic morphological changes, including the disruption of
      actin stress fibers, the loss of focal adhesion sites, membrane blebbing, and
      cell detachment. Treatment of SH-EP/pSFFV cells with IGF-I or transfection of IGF
      I receptor prevents these changes. Treatment of cells with pharmacologic
      inhibitors of the mitogen-activated protein kinase or phosphatidylinositol 3
      kinase pathways does not affect mannitol-induced FAK dephosphorylation and
      degradation. However, phosphatidylinositol 3-kinase is necessary for IGF-I
      mediated protection against FAK alteration. Mannitol treatment also results in
      the degradation of Akt. Mannitol induces the activation of caspases-3 and -9 in a
      time course similar to the dephosphorylation and degradation of FAK. Treatment of
      the cells with ZVAD, a general caspase inhibitor, blocks the mannitol-induced FAK
      and Akt degradation as well as cell detachment and apoptosis. These results
      suggest that one of the pathways of mannitol-mediated apoptosis is through the
      degradation of FAK and Akt and that IGF-I protects the cells from apoptosis by
      blocking the activation of caspases, which may be responsible for the loss of FAK
      and Akt.

PMID- 12011047
TI  - Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression
      of insulin gene expression.
AB  - Oxidative stress, which is found in pancreatic beta-cells in the diabetic state,
      suppresses insulin gene transcription and secretion, but the signaling pathways
      involved in the beta-cell dysfunction induced by oxidative stress remain unknown.
      In this study, subjecting rat islets to oxidative stress activates JNK, p38 MAPK,
      and protein kinase C, preceding the decrease of insulin gene expression.
      Adenovirus-mediated overexpression of dominant-negative type (DN) JNK, but not
      the p38 MAPK inhibitor SB203580 nor the protein kinase C inhibitor GF109203X,
      protected insulin gene expression and secretion from oxidative stress. Moreover,
      wild type JNK overexpression suppressed both insulin gene expression and
      secretion. These results were correlated with changes in the binding of the
      important transcription factor PDX-1 to the insulin promoter; adenoviral
      overexpression of DN-JNK preserved PDX-1 DNA binding activity in the face of
      oxidative stress, whereas wild type JNK overexpression decreased PDX-1 DNA
      binding activity. Furthermore, to examine whether suppression of the JNK pathway
      can protect beta-cells from the toxic effects of hyperglycemia, rat islets were
      infected with DN-JNK expressing adenovirus or control adenovirus and transplanted
      under renal capsules of streptozotocin-induced diabetic nude mice. In mice
      receiving DN-JNK overexpressing islets, insulin gene expression in islet grafts
      was preserved, and hyperglycemia was ameliorated compared with control mice. In
      conclusion, activation of JNK is involved in the reduction of insulin gene
      expression by oxidative stress, and suppression of the JNK pathway protects beta
      cells from oxidative stress.

PMID- 12011048
TI  - Vitamin D(3)-up-regulated protein-1 is a stress-responsive gene that regulates
      cardiomyocyte viability through interaction with thioredoxin.
AB  - The protein-disulfide reductase thioredoxin is critical for redox signaling
      during apoptosis and growth. In this study, we demonstrate that vitamin D(3)-up
      regulated protein-1 regulates thioredoxin in conditions of biomechanical or
      oxidative stress and critically regulates cardiomyocyte viability. Expression of
      vitamin D(3)-up-regulated protein-1 but not of thioredoxin in rat cardiomyocytes
      was rapidly suppressed by biomechanical strain or hydrogen peroxide at both mRNA
      and protein levels. Mechanical suppression of vitamin D(3)-up-regulated protein-1
      gene expression was blocked by N-acetylcysteine. The half-life of vitamin D(3)-up
      regulated protein-1 transcripts in cardiomyocytes was only 1.1 h and remained
      unchanged after mechanical stimulation, suggesting that rapid responses in
      vitamin D(3)-up-regulated protein-1 gene expression occur through transcriptional
      control. Vitamin D(3)-up-regulated protein-1 down-regulation by strain or
      hydrogen peroxide led to increased thioredoxin activity, whereas adenovirus
      mediated overexpression of vitamin D(3)-up-regulated protein-1 suppressed
      thioredoxin activity. Overexpression of vitamin D(3)-up-regulated protein-1 but
      not of thioredoxin induced cardiomyocyte apoptosis. Furthermore, overexpression
      of vitamin D(3)-up-regulated protein-1 sensitized cells to hydrogen peroxide
      induced apoptosis, whereas overexpression of thioredoxin protected against
      injury. These data identify vitamin D(3)-up-regulated protein-1 as a key stress
      responsive inhibitory switch of thioredoxin activity in cardiomyocytes and
      demonstrate that the vitamin D(3)-up-regulated protein-1/thioredoxin axis has an
      important role in the preservation of cellular viability.

PMID- 12011049
TI  - MEK mediates v-Src-induced disruption of the actin cytoskeleton via inactivation
      of the Rho-ROCK-LIM kinase pathway.
AB  - Cellular transformation by v-Src is believed to be caused by aberrant activation
      of signaling pathways that are normally regulated by cellular Src. Using normal
      rat kidney cells expressing a temperature-sensitive mutant of v-Src, we examined
      the role of the Raf/MEK/ERK, phosphatidylinositol 3-kinase/Akt, and Rho pathways
      in morphological transformation and cytoskeletal changes induced by v-Src.
      Activation of v-Src elicited a loss of actin stress fibers and focal contacts. A
      decrease in the phosphorylation level of cofilin was detected upon v-Src
      activation, which is indicative of attenuated Rho function. Inhibition of MEK
      using U0126 prevented v-Src-induced disruption of the cytoskeleton as well as
      dephosphorylation of cofilin, whereas treatment with a phosphatidylinositol 3
      kinase inhibitor had no protective effect. In normal rat kidney cells stably
      transformed by v-Src, we found that the chronic activation of MEK induces down
      regulation of ROCK expression, thereby uncoupling Rho from stress fiber
      formation. Taken together, these results establish MEK as an effector of v-Src
      induced cytoskeleton disruption, participating in v-Src-induced antagonism of the
      cellular function of Rho.

PMID- 12011050
TI  - Nematode anticoagulant protein c2 reveals a site on factor Xa that is important
      for macromolecular substrate binding to human prothrombinase.
AB  - The binding of recombinant nematode anticoagulant protein c2 (NAPc2) to either
      factor X or Xa is a requisite step in the pathway for the potent inhibition of
      VIIa tissue factor. We have used NAPc2 as a tight binding probe of human Xa to
      investigate protein substrate recognition by the human prothrombinase complex.
      NAPc2 binds with high affinity (K(d) approximately 1 nm) to both X and Xa in a
      way that does not require or occlude the active site of the enzyme. In contrast,
      NAPc2 is a tight binding, competitive inhibitor of protein substrate cleavage by
      human Xa incorporated into prothrombinase with saturating concentrations of
      membranes and Va. By fluorescence binding studies we show that NAPc2 does not
      interfere with the assembly of human prothrombinase. These are properties
      expected of an inhibitor that blocks protein substrate recognition by targeting
      extended macromolecular recognition sites (exosites) on the enzyme complex. A
      weaker interaction (K(d) = 260-500 nm) observed between NAPc2 and bovine X was
      restored to a high affinity one in a recombinant chimeric bovine X derivative
      containing 25 residues from the COOH terminus of the proteinase domain of human
      X. This region implicated in binding NAPc2 is spatially adjacent to a site
      previously identified as a potential exosite. Despite the weaker interaction with
      bovine Xa, NAPc2 was a tight binding competitive inhibitor of protein substrate
      cleavage by bovine prothrombinase as well. Extended enzymic surfaces elucidated
      with exosite-directed probes, such as NAPc2, may define a unique region of factor
      Xa that is modulated following its assembly into prothrombinase and in turn
      determines the binding specificity of the enzyme complex for its protein
      substrate.

PMID- 12011051
TI  - No evidence for a basal, retinoic, or superoxide-induced uncoupling activity of
      the uncoupling protein 2 present in spleen or lung mitochondria.
AB  - The phenotypes observed in mice whose uncoupling protein (Ucp2) gene had been
      invalidated by homologous recombination (Ucp2(-/-) mice) are consistent with an
      increase in mitochondrial membrane potential in macrophages and pancreatic beta
      cells. This could support an uncoupling (proton transport) activity of UCP2 in
      the inner mitochondrial membrane in vivo. We used mitochondria from lung or
      spleen, the two organs expressing the highest level of UCP2, to compare the
      proton leak of the mitochondrial inner membrane of wild-type and Ucp2(-/-) mice.
      No difference was observed under basal conditions. Previous reports have
      concluded that retinoic acid and superoxide activate proton transport by UCP2.
      Spleen mitochondria showed a higher sensitivity to retinoic acid than liver
      mitochondria, but this was not caused by UCP2. In contrast with a previous
      report, superoxide failed to increase the proton leak rate in kidney
      mitochondria, where no UCP2 expression was detected, and also in spleen
      mitochondria, which does not support stimulation of UCP2 uncoupling activity by
      superoxide. Finally, no increase in the ATP/ADP ratio was observed in spleen or
      lung of Ucp2(-/-) mice. Therefore, no evidence could be gathered for the
      uncoupling activity of the UCP2 present in spleen or lung mitochondria. Although
      this may be explained by difficulties with isolated mitochondria, it may also
      indicate that UCP2 has another physiological significance in spleen and lung.

PMID- 12011052
TI  - Structural basis of ordered binding of donor and acceptor substrates to the
      retaining glycosyltransferase, alpha-1,3-galactosyltransferase.
AB  - Bovine alpha-1,3-galactosyltransferase (alpha3GT) catalyzes the synthesis of the
      alpha-galactose (alpha-Gal) epitope, the target of natural human antibodies. It
      represents a family of enzymes, including the histo blood group A and B
      transferases, that catalyze retaining glycosyltransfer reactions of unknown
      mechanism. An initial study of alpha3GT in a crystal form with limited resolution
      and considerable disorder suggested the possible formation of a beta-galactosyl
      enzyme covalent intermediate (Gastinel, L. N., Bignon, C., Misra, A. K.,
      Hindsgaul, O., Shaper, J. H., and Joziasse, D. H. (2001) EMBO J. 20, 638-649).
      Highly ordered structures are described for complexes of alpha3GT with donor
      substrate, UDP-galactose, UDP- glucose, and two acceptor substrates, lactose and
      N-acetyllactosamine, at resolutions up to 1.46 A. Structural and calorimetric
      binding studies suggest an obligatory ordered binding of donor and acceptor
      substrates, linked to a donor substrate-induced conformational change, and the
      direct participation of UDP in acceptor binding. The monosaccharide-UDP bond is
      cleaved in the structures containing UDP-galactose and UDP-glucose, producing non
      covalent complexes containing buried beta-galactose and alpha-glucose. The
      location of these monosaccharides and molecular modeling suggest that binding of
      a distorted conformation of UDP-galactose may be important in the catalytic
      mechanism of alpha3GT.

PMID- 12011053
TI  - The C-terminal tails of HslU ATPase act as a molecular switch for activation of
      HslV peptidase.
AB  - The bacterial HslVU ATP-dependent protease is a homolog of the eukaryotic 26 S
      proteasome. HslU ATPase forms a hexameric ring, and HslV peptidase is a dodecamer
      consisting of two stacked hexameric rings. In HslVU complex, the HslU and HslV
      central pores are aligned, and the proteolytic active sites are sequestered in an
      internal chamber of HslV, with access to this chamber restricted to small axial
      pores. Here we show that the C-terminal tails of HslU play a critical role in the
      interaction with and activation of HslV peptidase. A synthetic tail peptide of 10
      amino acids could replace HslU in supporting the HslV-mediated hydrolysis of
      unfolded polypeptide substrates such as alpha-casein, as well as of small
      peptides, suggesting that the HslU C terminus is involved in the opening of the
      HslV pore for substrate entry. Moreover, deletion of 7 amino acids from the C
      terminus prevented the ability of HslU to form an HslVU complex with HslV. In
      addition, deletion of the C-terminal 10 residues prevented the formation of an
      HslU hexamer, indicating that the C terminus is required for HslU
      oligomerization. These results suggest that the HslU C-terminal tails act as a
      molecular switch for the assembly of HslVU complex and the activation of HslV
      peptidase.

PMID- 12011054
TI  - Disabling receptor ensembles with rationally designed interface peptidomimetics.
AB  - Members of the erbB family receptor tyrosine kinases (erbB1, erbB2, erbB3, and
      erbB4) are overexpressed in a variety of human cancers and represent important
      targets for the structure-based drug design. Homo- and heterodimerization
      (oligomerization) of the erbB receptors are known to be critical events for
      receptor signaling. To block receptor self-associations, we have designed a
      series of peptides derived from potential dimerization surfaces in the
      extracellular subdomain IV of the erbB receptors (erbB peptides). In surface
      plasmon resonance (BIAcore) studies, the designed peptides have been shown to
      selectively bind to the erbB receptor ectodomains and isolated subdomain IV of
      erbB2 with submicromolar affinities and to inhibit heregulin-induced interactions
      of erbB3 with different erbB receptors. A dose-dependent inhibition of native
      erbB receptor dimerization by the erbB peptides has been observed in 32D cell
      lines transfected with different combinations of erbB receptors. The peptides
      effectively inhibited growth of two types of transformed cells overexpressing
      different erbB receptors, T6-17 and 32D, in standard MTT (3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide) and cell viability assays. The study
      identifies distinct loops within the membrane-proximal part of the subdomain IV
      as potential receptor-receptor interaction sites for the erbB receptors and
      demonstrates the possibility of disabling receptor activity by structure-based
      targeting of the dimerization interfaces. Molecular models for possible
      arrangement of the erbB1.EGF complex, consistent with the involvement of
      subdomain IV in inter-receptor interactions, are proposed. Small dimerization
      inhibitors described herein can be useful as probes to elucidate different erbB
      signaling pathways and may be developed as therapeutic agents.

PMID- 12011055
TI  - A novel p53 transcriptional repressor element (p53TRE) and the asymmetrical
      contribution of two p53 binding sites modulate the response of the placental
      transforming growth factor-beta promoter to p53.
AB  - Previous studies in our laboratory and others identified placental transforming
      growth factor-beta (PTGF-beta) as an important downstream mediator of DNA damage
      signaling and a transcriptional target of p53. Here we show that accumulation of
      PTGF-beta mRNA in response to p53 overexpression is delayed relative to
      p21(WAF1), whereas the promoters of these genes respond to p53 with similar
      kinetics. Mutational analyses of two p53 binding sites within the PTGF-beta
      promoter revealed that site p53-1 (+29 bp) is responsible for as much as 80% of
      the transcriptional response to p53. This is consistent with electrophoretic
      mobility shift assays showing that site p53-1 binds p53 with a much higher
      affinity than site p53-2 (-850 bp). We also describe for the first time a novel
      21-bp element (-222 to -242 bp) that acts to down-regulate the PTGF-beta promoter
      response to p53. Termed the p53 transcriptional repressor element (p53TRE), this
      sequence was shown to suppress p53 transactivation in a position- and promoter
      independent fashion and to associate with a 28-kDa protein expressed in several
      tumor cell lines. A p53 suppressor element and asymmetric p53 binding sites may
      participate determining the activation thresholds of p53-responsive promoters in
      a cell- and context-specific manner.

PMID- 12011056
TI  - Differential regulation of cell migration, actin stress fiber organization, and
      cell transformation by functional domains of Crk-associated substrate.
AB  - The Crk-associated substrate (Cas) is a unique docking protein that possesses a
      repetitive stretch of tyrosine-containing motifs and an Src homology 3 (SH3)
      domain. Embryonic fibroblasts lacking Cas demonstrated resistance to Src-induced
      transformation along with impaired actin bundling and cell motility, indicating
      critical roles of Cas in actin cytoskeleton organization, cell migration, and
      oncogenesis. To gain further insight into roles of each domain of Cas in these
      processes, a compensation assay was performed by expressing a series of Cas
      mutants in Cas-deficient fibroblasts. The results showed that motifs containing
      YDxP were indispensable for actin cytoskeleton organization and cell migration,
      suggesting that CrkII-mediated signaling regulates these biological processes.
      The C-terminal Src-binding domain played essential roles in cell migration and
      membrane localization of Cas, although it was dispensable in the organization of
      actin stress fibers. Furthermore, the Src-binding domain was also a prerequisite
      for Src transformation possibly, because of its crucial role in the
      phosphorylation of Cas during transformation. Overall, differential uses of the
      Cas domains in individual biological processes were demonstrated.

PMID- 12011057
TI  - Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3
      and nectin 4 bind to the predicted C-C'-C"-D beta-strands of the nectin1 V
      domain.
AB  - Nectins form a family of integral molecules that belong to the immunoglobulin
      superfamily. Their ectodomain is made of three Ig-like domains (V, C, C). This
      family comprises at least five members, namely nectin1, -2, -3, -4, and
      poliovirus receptor (PVR), that are involved in different physiological and
      pathological processes. (i) Nectins are adhesion molecules localized at adherens
      junctions in epithelial cells. (ii) Some nectins act as poliovirus or alpha
      herpesvirus receptors (nectin1). (iii) Nectin1 mutations are involved in
      orofacial developmental abnormalities in humans. Adhesion properties of nectins
      are mediated by Ca(2+)-independent homophilic and heterophilic processes through
      ectodomain trans-interactions. We have described a nectin trans-hetero
      interaction network: nectin3 binds to nectin1, nectin2, and PVR; nectin1 also
      binds to nectin4. In the present study we compared the affinities of the
      different trans-interactions mediated by nectin1. We found that the K(D) of
      nectin1/nectin3 and nectin1/nectin4 interactions is 1 and 100 nm, respectively,
      whereas the K(D) of the nectin1-mediated homophilic interaction is 1 microm. We
      show that nectin1/nectin3 and nectin1/nectin4 trans-hetero-interactions were
      mediated through trans V to V domain interactions, whereas C domains contributed
      to increase the affinity of the interaction. Nectin3 and nectin4 share a common
      binding region in the nectin1 V domain: (i) nectin3 strongly competed with
      nectin4 binding, (ii) nectin3 and nectin4 binding to nectin1 was reduced by a
      number of monoclonal antibodies directed against the nectin1 V domain, and (iii)
      the glycoprotein D of herpes simplex virus-1 that binds to the V domain of
      nectin1 reduced nectin3 and nectin4 binding. Finally, using chimeric nectin1/PVR
      receptors where PVR V domain beta-strands were substituted with the corresponding
      regions of nectin1, the nectin3 and nectin4 minimal binding region on nectin1 V
      domain was mapped to the C-C'-C"-D beta-strands.

PMID- 12011058
TI  - Isolation and characterization of the putative nuclear modifier gene MTO1
      involved in the pathogenesis of deafness-associated mitochondrial 12 S rRNA
      A1555G mutation.
AB  - The human mitochondrial 12 S rRNA A1555G mutation has been found to be associated
      with aminoglycoside-induced and non-syndromic deafness. However, putative nuclear
      modifier gene(s) have been proposed to regulate the phenotypic expression of this
      mutation. In yeast, the mutant alleles of MTO1, encoding a mitochondrial protein,
      manifest respiratory-deficient phenotype only when coupled with the mitochondrial
      15 S rRNA P(R)454 mutation corresponding to human A1555G mutation. This suggests
      that the MTO1-like modifier gene may influence the phenotypic expression of human
      A1555G mutation. Here we report the identification of full-length cDNA and
      elucidation of genomic organization of the human MTO1 homolog. Human Mto1 is an
      evolutionarily conserved protein that implicates a role in the mitochondrial tRNA
      modification. Functional conservation of this protein is supported by the
      observation that isolated human MTO1 cDNA can complement the respiratory
      deficient phenotype of yeast mto1 cells carrying P(R)454 mutation. MTO1 is
      ubiquitously expressed in various tissues, but with a markedly elevated
      expression in tissues of high metabolic rates including cochlea. These
      observations suggest that human MTO1 is a structural and functional homolog of
      yeast MTO1. Thus, it may play an important role in the pathogenesis of deafness
      associated A1555G mutation in 12 S rRNA gene or mutations in tRNA genes.

PMID- 12011059
TI  - Low molecular weight peptides restore the procoagulant activity of factor VIII in
      the presence of the potent inhibitor antibody ESH8.
AB  - Following repeated administration of factor VIII (FVIII), a significant number of
      hemophilia A patients develop antibodies (Abs), inhibiting the procoagulant
      activity of infused FVIII. We have designed an approach based on the blocking of
      the deleterious activity of these Abs by peptide decoys mimicking the anti-FVIII
      Ab epitopes. Here, the well characterized inhibitory monoclonal Ab ESH8 served as
      a model. Several phage peptide libraries were screened for specific binding to
      ESH8. Seven constrained dodecapeptide sequences were obtained. Six sequences
      carried the consensus motif, hydrophobic-(Y/F)GKTXL. This motif showed a certain
      similarity with the (2231)QVDFQKTMKV(2240) sequence of the C(2) domain. In the
      seventh sequence, YCNPSIGDKNCR, the residues GDKN are similar to the sequence
      (2267)DGHQ(2270). Upon inspection of the C(2) domain crystallographic structure,
      the two stretches QVDFQKTMKV and DGHQ appeared close together in space and might
      constitute a discontinuous epitope. Corresponding synthetic peptides were able to
      inhibit the binding of ESH8 to FVIII in a specific and dose-dependent manner.
      Moreover, the ability of the selected peptides to neutralize the inhibitory
      activity of ESH8 was demonstrated in functional tests as well as in vivo in a
      murine model of hemophilia A. This study demonstrates the potential of this
      approach to neutralize the activity of potent inhibitory Abs.

PMID- 12011060
TI  - Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results
      in synergistic activation of the human lactase-phlorizin hydrolase promoter.
AB  - GATA-4, -5, and -6 zinc finger and hepatocyte nuclear factor-1alpha (HNF-1alpha)
      homeodomain transcription factors are expressed in the intestinal epithelium and
      synergistically activate the promoter of intestinal genes. Here, we demonstrate
      that GATA-5 and HNF-1alpha physically associate both in vivo and in vitro and
      that this interaction is necessary for cooperative activation of the lactase
      phlorizin hydrolase promoter. Furthermore, physical association is mediated by
      the C-terminal zinc finger of GATA factors and the homeodomain of HNF-1alpha.
      Deletion of HNF-1alpha activation domains or interruption of HNF-1-binding sites
      in the lactase-phlorizin hydrolase promoter resulted in a complete loss of
      cooperativity, whereas deletion of GATA-5 activation domains or interruption of
      GATA-binding sites resulted in a reduction, but not an elimination, of
      cooperativity. We hypothesize that GATA/HNF-1alpha cooperativity is mediated by
      HNF-1alpha through its activation domains, which are oriented for high levels of
      activation through binding to DNA and physical association with GATA factors.
      These data suggest a paradigm whereby intestine-specific gene expression is
      regulated by unique interactions among tissue-restricted transcription factors
      coexpressed in the intestine. Parallel mechanisms in other tissues as well as in
      Drosophila suggest that zinc finger/homeodomain interactions are an efficient
      pathway of cooperative activation of gene transcription that has been conserved
      throughout evolution.

PMID- 12011061
TI  - Transforming growth factor-beta 2 is a transcriptional target for Akt/protein
      kinase B via forkhead transcription factor.
AB  - Tumors evade cell death by constitutively activating cell survival pathways and
      suppressing intrinsic death machinery. Activation of cell survival pathways leads
      to transcriptional repression of genes associated with cell death and activation
      of ones promoting anti-apoptosis. Akt/protein kinase B phosphorylates forkhead
      transcription factors and prevents their nuclear localization, leading to
      repression of genes involved in apoptosis, such as Fas ligand (FasL). Using
      bioinformatic approaches, we have identified three consensus sequences for
      forkhead transcription factor binding in transforming growth factor beta2 (TGF
      beta2) promoter. TGF-beta inhibits cell proliferation and induces apoptosis in
      many cell types, and acquisition of TGF-beta resistance is linked to
      tumorigenesis. In this study, we show that activated Akt down-regulates TGF-beta2
      promoter, and sequences within the promoter that are related to consensus
      forkhead binding sites are necessary for repression. Forkhead factor FKHRL1 binds
      in vitro to the three consensus sequences and can activate TGF-beta2 promoter in
      normal and Akt-transformed cell lines. In human breast and pancreatic tumors,
      activated Akt expression correlated with down-regulation of TGF-beta 2 mRNA
      levels. A number of tumor cells expressing activated Akt were responsive to TGF
      beta addition, indicating the presence of an intact TGF-beta-signaling pathway.
      These results suggest that repression of TGF-beta 2 promoter activity in cells
      expressing activated Akt may play a role in promoting tumorigenesis and escape
      from the growth-inhibitory and/or apoptotic effects of TGF-beta.

PMID- 12011062
TI  - Store depletion-activated CaT1 currents in rat basophilic leukemia mast cells are
      inhibited by 2-aminoethoxydiphenyl borate. Evidence for a regulatory component
      that controls activation of both CaT1 and CRAC (Ca(2+) release-activated Ca(2+)
      channel) channels.
AB  - The intestinal Ca(2+) transport protein CaT1 encoded by TRPV6 has been reported
      (Yue, L., Peng, J. B., Hediger, M. A., and Clapham, D. E. (2001) Nature 410, 705
      709) to be all or a part of the Ca(2+) release-activated Ca(2+) channel (CRAC).
      The major characteristic of CRAC is its activation following store depletion. We
      expressed CaT1 in HEK293 cells and rat basophilic leukemia (RBL) mast cells and
      measured whole-cell currents by the patch clamp technique. In HEK293 cells, the
      expression of CaT1 consistently yielded a constitutively active current, the size
      of which was strongly dependent on the holding potential and duration of voltage
      ramps. In CaT1-expressing RBL cells, the current was either activated by store
      depletion or was constitutively active at a higher current density. CaT1 currents
      could be clearly distinguished from endogenous CRAC by their typical current
      voltage relationship in divalent free solution. 2-aminoethoxydiphenyl borate (2
      APB), which is considered a blocker of CRAC, was tested for its inhibitory effect
      on both cell types expressing CaT1. Endogenous CRAC as well as store-dependent
      CaT1-derived currents of RBL cells were largely blocked by 75 microm 2-APB,
      whereas constitutively active CaT1 currents in both RBL and HEK293 cells were
      slightly potentiated. These results indicate that despite the difference in the
      permeation properties of CRAC and CaT1 channels, the latter are similarly able to
      form store depletion-activated conductances in RBL mast cells that are inhibited
      by 2-APB.

PMID- 12011063
TI  - Calcium oscillations trigger focal adhesion disassembly in human U87 astrocytoma
      cells.
AB  - Integrin-associated intracellular Ca(2+) oscillations modulate cell migration,
      probably by controlling integrin-mediated release of the cell rear during
      migration. Focal adhesion kinase (FAK), via its tyrosine phosphorylation
      activity, plays a key role in integrin signaling. In human U87 astrocytoma cells,
      expression of the dominant negative FAK-related non-kinase domain (FRNK) inhibits
      the Ca(2+)-sensitive component of serum-dependent migration. We investigated how
      integrin-associated Ca(2+) signaling might be coupled to focal adhesion (FA)
      dynamics by visualizing the effects of Ca(2+) spikes on FAs using green
      fluorescent protein (GFP)-tagged FAK and FRNK. We report that Ca(2+) spikes are
      temporally correlated with movement and disassembly of FAs, but not their
      formation. FRNK transfection did not affect generation of Ca(2+) spikes, although
      cell morphology was altered, with fewer FAs of larger size and having a more
      peripheral localization being observed. Larger sized FAs in FRNK-transfected
      cells were not disassembled by Ca(2+) spikes, providing a possible explanation
      for impaired Ca(2+)-dependent migration in these cells. Stress fiber end
      movements initiated by Ca(2+) spikes were visualized using GFP-tagged myosin
      light chain kinase (MLCK). Ca(2+)-associated movements of stress fiber ends and
      FAs had similar kinetics, suggesting that stress fibers and FAs move in a
      coordinated fashion. This indicates that increases in Ca(2+) likely trigger
      disassembly of adhesive structures that involves disruption of integrin
      extracellular matrix interactions, supporting a key role for Ca(2+)-sensitive
      inside-out signaling in cell migration. A rapid increase in tyrosine
      phosphorylation of FAK was found in response to an elevation in Ca(2+) induced by
      thapsigargin, and we propose that this represents the initial triggering event
      linking Ca(2+) signaling and FA dynamics to cell motility.

PMID- 12011064
TI  - Orientational constraints of the gp130 intracellular juxtamembrane domain for
      signaling.
AB  - The glycoprotein 130 (gp130) is the common signal transducing receptor chain of
      the interleukin-6 family of cytokines. Here we investigated the requirements for
      transfer of the information given by ligand binding to the cytoplasmic domain of
      gp130. It is demonstrated that the box 1/2 region has to be located membrane
      proximally in order to bind and activate Janus kinases. To test the possible
      requirement of an alpha-helical orientation, we inserted 1-4 alanine residues
      into this juxtamembrane intracellular region. The insertion of one alanine
      results in a strongly reduced activation of STAT1 and STAT3, whereas insertion of
      three alanine residues leads to a stronger STAT activation. These results suggest
      that gp130-mediated activation of STATs is sensitive to rotational changes around
      the receptor axis perpendicular to the membrane. Surprisingly, insertion of 1, 2,
      3, or 4 alanine residues into this juxtamembrane region leads to successive
      impairment but not abolishment of Janus kinase and receptor phosphorylation,
      supporting the finding of sensitivity of Janus kinases toward changes in distance
      of box 1/2 from the plasma membrane. We suggest a new model concerning the gp130
      activation mode in which the relative orientation of the cytoplasmic regions
      seems to be critical for further signal transduction.

PMID- 12011065
TI  - Identification of the catalytic residues of alpha-amino acid ester hydrolase from
      Acetobacter turbidans by labeling and site-directed mutagenesis.
AB  - The alpha-amino acid ester hydrolase from Acetobacter turbidans ATCC 9325 is
      capable of hydrolyzing and synthesizing the side chain peptide bond in beta
      lactam antibiotics. Data base searches revealed that the enzyme contains an
      active site serine consensus sequence Gly-X-Ser-Tyr-X-Gly that is also found in X
      prolyl dipeptidyl aminopeptidase. The serine hydrolase inhibitor p-nitrophenyl-p'
      guanidino-benzoate appeared to be an active site titrant and was used to label
      the alpha-amino acid ester hydrolase. Electrospray mass spectrometry and tandem
      mass spectrometry analysis of peptides from a CNBr digest of the labeled protein
      showed that Ser(205), situated in the consensus sequence, becomes covalently
      modified by reaction with the inhibitor. Extended sequence analysis showed
      alignment of this Ser(205) with the catalytic nucleophile of some alpha/beta
      hydrolase fold enzymes, which posses a catalytic triad composed of a nucleophile,
      an acid, and a base. Based on the alignments, 10 amino acids were selected for
      site-directed mutagenesis (Arg(85), Asp(86), Tyr(143), Ser(156), Ser(205),
      Tyr(206), Asp(338), His(370), Asp(509), and His(610)). Mutation of Ser(205),
      Asp(338,) or His(370) to an alanine almost fully inactivated the enzyme, whereas
      mutation of the other residues did not seriously affect the enzyme activity.
      Circular dichroism measurements showed that the inactivation was not caused by
      drastic changes in the tertiary structure. Therefore, we conclude that the
      catalytic domain of the alpha-amino acid ester hydrolase has an alpha/beta
      hydrolase fold structure with a catalytic triad of Ser(205), Asp(338), and
      His(370). This distinguishes the alpha-amino acid ester hydrolase from the Ntn
      hydrolase family of beta-lactam antibiotic acylases.

PMID- 12011066
TI  - Placental alkaline phosphatase is efficiently targeted to rafts in supported
      lipid bilayers.
AB  - Evidence is growing that biological membranes contain lipid microdomains or
      "rafts" that may be involved in processes such as cellular signaling and protein
      trafficking. In this study, we have used atomic force microscopy to examine the
      behavior of rafts in supported lipid bilayers. We show that bilayers composed of
      equimolar dioleoylphosphatidylcholine and sphingomyelin spontaneously form rafts,
      which are detectable as raised features. A comparison of the extents of
      protrusion of the rafts in monolayers and bilayers indicates that the rafts in
      the two leaflets of the bilayer coincide. The rafts were observed both in the
      absence and presence of cholesterol (33 mol %). Cholesterol reduced raft
      protrusion presumably by increasing the thickness of the non-raft bilayer. PLAP
      (glycosylphosphatidylinositol-anchored protein placental alkaline phosphatase)
      was purified and shown to exist as a dimer. Following its incorporation into
      supported lipid bilayers, PLAP was found to be targeted efficiently to rafts,
      both in the absence and presence of cholesterol. We suggest that atomic force
      microscopy provides a powerful tool for the study of raft structure and
      properties.

PMID- 12011067
TI  - Mediation of the DCC apoptotic signal by DIP13 alpha.
AB  - DCC (deleted in colorectal cancer) is a candidate tumor suppressor gene. However
      the function of DCC remains elusive. Previously, we demonstrated that forced
      expression of DCC induces apoptosis or cell cycle arrest (Chen, Y. Q., Hsieh, J.
      T., Yao, F., Fang, B., Pong, R. C., Cipriano, S. C. & Krepulat, F. (1999)
      Oncogene 18, 2747-2754). To delineate the DCC-induced apoptotic pathway, we have
      identified a protein, DIP13 alpha, which interacts with DCC. The DIP13 alpha
      protein has a pleckstrin homology domain and a phosphotyrosine binding domain. It
      interacts with a region on the DCC cytoplasmic domain that is required for the
      induction of apoptosis. Although ectopic expression of DIP13 alpha alone causes
      only a slight increase in apoptosis, co-expression of DCC and DIP13 alpha results
      in an approximately 5-fold increase in apoptosis. Removal of the DCC-interacting
      domain on DIP13 alpha abolishes its ability to enhance DCC-induced apoptosis.
      Inhibition of endogenous DIP13 alpha expression by small interfering RNA blocks
      DCC-induced apoptosis. Our data suggest that DIP13 alpha is a mediator of the DCC
      apoptotic pathway.

PMID- 12011068
TI  - Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated
      by Dark and DRONC.
AB  - Members of the inhibitor of apoptosis protein (IAP) family can inhibit caspases
      and cell death in a variety of insect and vertebrate systems. Drosophila IAP1
      (DIAP1) inhibits cell death to facilitate normal embryonic development. Here,
      using RNA interference, we showed that down-regulation of DIAP1 is sufficient to
      induce cell death in Drosophila S2 cells. Although this cell death process was
      accompanied by elevated caspase activity, this activation was not essential for
      cell death. We found that DIAP1 depletion-induced cell death was strongly
      suppressed by a reduction in the Drosophila caspase DRONC or the Drosophila
      apoptotic protease-activating factor-1 (Apaf-1) homolog, Dark. RNA interference
      studies in Drosophila embryos also demonstrated that the action of Dark is
      epistatic to that of DIAP1 in this cell death pathway. The cell death caused by
      down-regulation of DIAP1 was accelerated by overexpression of DRONC and Dark, and
      a caspase-inactive mutant form of DRONC could functionally substitute the wild
      type DRONC in accelerating cell death. These results suggest the existence of a
      novel mechanism for cell death signaling in Drosophila that is mediated by DRONC
      and Dark.

PMID- 12011069
TI  - Activation of BAD by therapeutic inhibition of epidermal growth factor receptor
      and transactivation by insulin-like growth factor receptor.
AB  - Novel cancer chemotherapeutics are required to induce apoptosis by activating pro
      apoptotic proteins. Both epidermal growth factor (EGF) and insulin-like growth
      factor (IGF) provide potent survival stimuli in many epithelia, and activation of
      their receptors is commonly observed in solid human tumors. Here we demonstrate
      that blockade of the EGF receptor by a new drug in phase III clinical trails for
      cancer, ZD1839, potently induces apoptosis in mammary epithelial cell lines and
      primary cultures, as well as in a primary pleural effusion from a breast cancer
      patient. We identified the mechanism of apoptosis induction by ZD1839. We showed
      that it prevents cell survival by activating the pro-apoptotic protein BAD.
      Moreover, we demonstrate that IGF transactivates the EGF receptor and that ZD1839
      blocks IGF-mediated phosphorylation of MAPK and BAD. Many cancer therapies kill
      tumor cells by inducing apoptosis as a consequence of targeting DNA; however, the
      threshold at which apoptosis can be triggered through DNA damage is often
      different from that in normal cells. Our results indicate that by targeting a
      growth factor-mediated survival signaling pathway, BAD phosphorylation can be
      manipulated therapeutically to induce apoptosis.

PMID- 12011070
TI  - Transforming growth factor-beta induces expression of receptor activator of NF
      kappa B ligand in vascular endothelial cells derived from bone.
AB  - Vascular endothelial cells in bone are thought to have significant roles on
      pathological bone resorption such as bone metastasis and hypercalcemia because
      this resorption is often seen where blood vessels are abundant. However, the
      detailed mechanisms have not yet been elucidated. Here, we focused on
      transforming growth factor-beta (TGF-beta) and studied its effects on vascular
      endothelial cells because TGF-beta is abundantly stored in bone matrix and is
      released and activated during bone resorption. We found that TGF-beta up
      regulated the expression of receptor activator of NF-kappa B ligand (RANKL) mRNA
      and protein in bone marrow-derived endothelial cells and in primary vascular
      endothelial cells but not in osteoblasts. Further analysis revealed that TGF-beta
      promoted phosphorylation of cAMP response element-binding protein and p38.
      Protein kinase A inhibitor KT5720 and p38 inhibitor SB203580 significantly
      reduced the TGF-beta-induced RANKL expression. Moreover, we found two CRE-like
      domains in murine RANKL promoter region that were critical for TGF-beta-dependent
      RANKL expression. Therefore, protein kinase A and p38 signaling pathways are
      involved in TGF-beta-induced RANKL expression by stimulating transcription
      factors that bind to the CRE-like domains. Our findings indicate that TGF-beta
      stimulates osteoclastogenesis by promoting RANKL expression in endothelial cells
      under pathological conditions.

PMID- 12011071
TI  - Structural basis of thermostability. Analysis of stabilizing mutations in
      subtilisin BPN'.
AB  - The crystal structures of two thermally stabilized subtilisin BPN' variants, S63
      and S88, are reported here at 1.8 and 1.9 A resolution, respectively. The
      micromolar affinity calcium binding site (site A) has been deleted (Delta75-83)
      in these variants, enabling the activity and thermostability measurements in
      chelating conditions. Each of the variants includes mutations known previously to
      increase the thermostability of calcium-independent subtilisin in addition to new
      stabilizing mutations. S63 has eight amino acid replacements: D41A, M50F, A73L,
      Q206W, Y217K, N218S, S221C, and Q271E. S63 has 75-fold greater stability than
      wild type subtilisin in chelating conditions (10 mm EDTA). The other variant,
      S88, has ten site-specific changes: Q2K, S3C, P5S, K43N, M50F, A73L, Q206C,
      Y217K, N218S, and Q271E. The two new cysteines form a disulfide bond, and S88 has
      1000 times greater stability than wild type subtilisin in chelating conditions.
      Comparisons of the two new crystal structures (S63 in space group P2(1) with A
      cell constants 41.2, 78.1, 36.7, and beta = 114.6 degrees and S88 in space group
      P2(1)2(1)2(1) with cell constants 54.2, 60.4, and 82.7) with previous structures
      of subtilisin BPN' reveal that the principal changes are in the N-terminal
      region. The structural bases of the stabilization effects of the new mutations
      Q2K, S3C, P5S, D41A, Q206C, and Q206W are generally apparent. The effects are
      attributed to the new disulfide cross-link and to improved hydrophobic packing,
      new hydrogen bonds, and other rearrangements in the N-terminal region.

PMID- 12011072
TI  - Clustering of CD40 ligand is required to form a functional contact with CD40.
AB  - Receptor clustering is a key event in the initiation of signaling by many types
      of receptor molecules. Here, we provide evidence for the novel concept that
      clustering of a ligand is a prerequisite for clustering of the cognate receptor.
      We show that clustering of the CD40 receptor depends on reciprocal clustering of
      the CD40 ligand (gp39, CD154). Clustering of the CD40 ligand is mediated by an
      association of the ligand with p53, a translocation of acid sphingomyelinase
      (ASM) to the cell membrane, an activation of the ASM, and a formation of
      ceramide. Ceramide appears to modify preexisting sphingolipid-rich membrane
      microdomains to fuse and form ceramide-enriched signaling platforms that serve to
      cluster CD40 ligand. Genetic deficiency of p53 or ASM or disruption of ceramide
      enriched membrane domains prevents clustering of CD40 ligand. The functional
      significance of CD40 ligand clustering is indicated by the finding that
      clustering of CD40 on B lymphocytes upon co-incubation with CD40 ligand
      expressing T cells depends on clustering of the CD40 ligand and is abrogated by
      inhibition of CD40 ligand clustering.

PMID- 12011073
TI  - Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose)
      polymerase-1 protein and are poly(ADP-ribosyl)ated.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is activated by DNA strand breaks during
      cellular genotoxic stress response and catalyzes poly(ADP-ribosyl)ation of
      acceptor proteins. These acceptor proteins include those involved in modulation
      of chromatin structure, DNA synthesis, DNA repair, transcription, and cell cycle
      control. Thus, PARP-1 is believed to play a pivotal role in maintaining genome
      integrity through modulation of protein-protein and protein-DNA interactions. We
      previously described the association of PARP-1 with normal mammalian centromeres
      and human neocentromeres by affinity purification and immunofluorescence. Here we
      investigated the interaction of this protein with, and poly(ADP-ribosyl)ation of,
      three constitutive centromere proteins, Cenpa, Cenpb, and Cenpc, and a spindle
      checkpoint protein, Bub3. Immunoprecipitation and Western blot analyses
      demonstrate that Cenpa, Cenpb, and Bub3, but not Cenpc, interacted with PARP-1,
      and are poly(ADP-ribosyl)ated following induction of DNA damage. The results
      suggest a role of PARP-1 in centromere assembly/disassembly and checkpoint
      control. Demonstration of PARP-1-binding and poly(ADP-ribosyl)ation in three of
      the four proteins tested further suggests that many more centromere proteins may
      behave similarly and implicates PARP-1 as an important regulator of diverse
      centromere function.

PMID- 12011074
TI  - Relief of extrinsic pathway inhibition by the Bid-dependent mitochondrial release
      of Smac in Fas-mediated hepatocyte apoptosis.
AB  - The mitochondrial pathway is critical for the efficient execution of death
      receptor-initiated apoptosis in certain cell types. Questions remain as to why
      the mitochondria are required in that scenario. We investigated the molecular
      events that determined the need for the mitochondria by using an in vivo model of
      anti-Fas-induced hepatocyte apoptosis. In wild-type mice, Fas stimulation
      resulted in normal activation of caspase-3, with the generation of the active p19
      p12 complex. In bid-deficient mice, caspase-3 activation was arrested after the
      initial cleavage at Asp(175). This allowed the generation of the p12 small
      subunit, but the p20 large subunit could not be further processed to the p19
      subunit. The p20-p12 complex generated by Fas stimulation in bid-deficient
      hepatocytes was inactive, arresting the death program. Failure of p20/p12 caspase
      3 to mature and to exhibit activity was because of the inhibition by the
      inhibitor-of-apoptosis proteins (IAPs), such as XIAP, and also to a low caspase-8
      activity. This block could be overcome in wild-type mice by two mechanisms. Smac
      was released from mitochondria early following Fas activation and was
      competitively bound to the IAPs to reverse their effects. XIAP could also be
      cleaved, and this occurred later and was likely mediated by enhanced caspase
      activities. Both mechanisms were dependent on Bid and thus were not operative in
      bid-deficient hepatocytes. In conclusion, mitochondrial activation by Bid is
      required for reversing the IAP inhibition through Smac release. It is also
      required for the alternative activation of caspases through cytochrome c release,
      as demonstrated previously. Together, these events ensure a successful
      progression of the death program initiated by the death receptor activation in
      the hepatocyte.

PMID- 12011075
TI  - Hyaluronan binding properties of a CD44 chimera containing the link module of TSG
      6.
AB  - CD44, a cell-surface receptor for the extracellular matrix glycosaminoglycan
      hyaluronan, can mediate leukocyte rolling on hyaluronan substrates and has been
      implicated in leukocyte migration to sites of inflammation. CD44-mediated binding
      to hyaluronan is of low affinity, and effective cell/matrix interaction depends
      on multiple interactions with the multivalent ligand. We replaced the Link module
      of CD44 with the homologous region of TSG-6, a hyaluronan-binding protein
      secreted in response to inflammation whose Link module has a higher affinity for
      ligand. Monoclonal antibodies raised against the CD44/TSG-6 chimera recognized
      recombinant human TSG-6 and native mouse TSG-6 and blocked hyaluronan binding to
      these proteins. Cells expressing the CD44/TSG-6 molecule bound hyaluronan with
      higher avidity than cells expressing CD44. This resulted in changes in the
      hyaluronan binding properties characteristic of cells expressing CD44 such as
      requirements for threshold levels of receptor expression and for hyaluronan of
      high molecular mass. In parallel plate flow assays used to model leukocyte
      rolling, cells expressing CD44/TSG-6 failed to roll on hyaluronan. Instead, they
      stuck and remained "tethered" to the substrate under fluid flow. This result
      argues that the low affinity of CD44 for its ligand is important for rolling, an
      early phase of leukocyte extravasation from the blood.

PMID- 12011076
TI  - Putidaredoxin reductase, a new function for an old protein.
AB  - Properties of recombinant wild type (WT) and six-histidine tag-fused (His(6))
      putidaredoxin reductase (Pdr), a FAD-containing component of the soluble
      cytochrome P450cam monooxygenase system from Pseudomonas putida, have been
      studied. Both WT and His(6) Pdr were found to undergo a monomer-dimer association
      dissociation and were partially present as an NAD(+)-bound form. Although
      molecular, spectral, and electron transferring properties of recombinant His(6)
      Pdr to artificial and native electron acceptors were similar to those of the WT
      protein, the presence of eight additional C-terminal amino acid residues, Pro-Arg
      His-His-His-His-His-His, had a crucial effect on the enzyme interaction with
      oxidized pyridine nucleotide. Under anaerobic conditions, NAD(+) induced in
      His(6) Pdr spectral changes indicative of flavin reduction and formation of the
      charge transfer complex between the reduced FAD and NAD(+). The reaction
      proceeded considerably faster in the presence of free histidine and thiol
      reducing agents, such as dithiothreitol and reduced glutathione. In the presence
      of any of these three reagents, NAD(+) was capable of inducing reduction of the
      flavin in WT Pdr. Free thiol groups were identified as an internal source of
      electrons in the enzyme. The results showed that WT and His(6) Pdr were able to
      function as NAD(H)-dependent dithiol/disulfide oxidoreductases catalyzing both
      forward and reverse reactions, NAD(+)-dependent oxidation of thiols, and NADH
      dependent reduction of disulfides. This function of the flavoprotein can be
      dissociated from electron transfer to putidaredoxin. Similarity of Pdr to the
      enzymes of the glutathione reductase family is discussed.

PMID- 12011077
TI  - BRCA1 regulates the interferon gamma-mediated apoptotic response.
AB  - BRCA1 is a tumor suppressor gene implicated in transcriptional regulation. We
      have generated cell lines with inducible expression of BRCA1 as a tool to
      identify downstream targets that may be important mediators of BRCA1 function.
      Oligonucleotide array-based expression profiling identified 11 previously
      described interferon regulated genes that were up-regulated following inducible
      expression of BRCA1. Northern blot analysis revealed that a subset of the
      identified targets including IRF-7, MxA, and ISG-54 were synergistically up
      regulated by BRCA1 in the presence of interferon gamma (IFN-gamma) but not
      interferons alpha or beta. Importantly, IFN-gamma-mediated induction of IRF-7 and
      MxA was attenuated in the BRCA1 mutant cell line HCC1937, an effect that was
      rescued following reconstitution of exogenous wild type BRCA1 in these cells.
      Furthermore, reconstituted BRCA1 sensitized HCC1937 cells to IFN-gamma-induced
      apoptotic cell death. This study identifies BRCA1 as a component of the IFN-gamma
      regulated signaling pathway and suggests that BRCA1 may play a role in the
      regulation of IFN-gamma-mediated apoptosis.

PMID- 12011078
TI  - Bacillus subtilis CheD is a chemoreceptor modification enzyme required for
      chemotaxis.
AB  - The chemotaxis machinery of Bacillus subtilis is similar to that of the well
      characterized system of Escherichia coli. However, B. subtilis contains several
      chemotaxis genes not found in the E. coli genome, such as cheC and cheD,
      indicating that the B. subtilis chemotactic system is more complex. In B.
      subtilis, CheD is required for chemotaxis; the cheD mutant displays a tumbly
      phenotype, has abnormally methylated chemoreceptors, and responds poorly to most
      chemical stimuli. Homologs of B. subtilis CheD have been found in chemotaxis-like
      operons of a large number of bacteria and archaea, suggesting that CheD plays an
      important role in chemotactic sensory transduction for many organisms. However,
      the molecular function of CheD has remained unknown. In this study, we show that
      CheD catalyzes amide hydrolysis of specific glutaminyl side chains of the B.
      subtilis chemoreceptor McpA. In addition, we present evidence that CheD
      deamidates other B. subtilis chemoreceptors including McpB and McpC. Previously,
      deamidation of B. subtilis receptors was thought to be catalyzed by the CheB
      methylesterase, as is the case for E. coli receptors. Because cheD mutant cells
      do not respond to most chemoattractants, we conclude that deamidation by CheD is
      required for B. subtilis chemoreceptors to effectively transduce signals to the
      CheA kinase.

PMID- 12011079
TI  - Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand
      induced endocytosis of the epidermal growth factor receptor.
AB  - Endocytosis of ligand-activated receptors requires dynamin-mediated GTP
      hydrolysis, which is regulated by dynamin self-assembly. Here, we demonstrate
      that phosphorylation of dynamin I by c-Src induces its self-assembly and
      increases its GTPase activity. Electron microscopic analyses reveal that tyrosine
      phosphorylated dynamin I spontaneously self-assembles into large stacks of rings.
      Tyrosine 597 was identified as being phosphorylated both in vitro and in cultured
      cells following epidermal growth factor receptor stimulation. The replacement of
      tyrosine 597 with phenylalanine impairs Src kinase-induced dynamin I self
      assembly and GTPase activity in vitro. Expression of Y597F dynamin I in cells
      attenuates agonist-driven epidermal growth factor receptor internalization. Thus,
      c-Src-mediated tyrosine phosphorylation is required for the function of dynamin
      in ligand-induced signaling receptor internalization.

PMID- 12011080
TI  - Multiple mechanisms for Pitx-1 transactivation of a luteinizing hormone beta
      subunit gene.
AB  - The pituitary homeobox factor-1 (Pitx-1) transactivates a number of pituitary
      specific genes through direct interaction with other specific transcription
      factors. We demonstrate here that Pitx-1 plays a crucial role in the regulation
      of the Chinook salmon luteinizing hormone beta gene promoter through a number of
      novel mechanisms. On the proximal promoter its action involves a synergistic
      effect with steroidogenic factor-1 (SF-1) alone or in combination with the
      estrogen receptor; promoter activity being induced by 9- or 35-fold over
      controls, respectively. Further upstream, a series of four Pitx-1 response
      elements (located between 1366 and 1506 bp from the transcriptional start site)
      is also involved in regulating the promoter activity. The two distal sequences
      have the greatest effect on the basal activity and are also essential for the
      gonadotropin-releasing hormone (GnRH) response. Mammalian two-hybrid assays
      revealed that Pitx-1 can homodimerize. Moreover, circular permutation assays
      indicate that binding of Pitx-1 to more than one response element induces
      conformational changes of the target DNA. This constitutes an additional
      mechanism through which Pitx-1 can mediate transactivation of this gene, allowing
      the demonstrated interaction of proximal response elements and distal enhancers,
      thus facilitating the maximal GnRH response that was seen in the longer promoter
      constructs. Our research also indicates that Pitx-1 is phosphorylated on three
      residues when bound to the DNA.

PMID- 12011081
TI  - Hyperphenylalaninemia and impaired glucose tolerance in mice lacking the
      bifunctional DCoH gene.
AB  - The bifunctional protein DCoH (Dimerizing Cofactor for HNF1) acts as an enzyme in
      intermediary metabolism and as a binding partner of the HNF1 family of
      transcriptional activators. HNF1 proteins direct the expression of a variety of
      genes in the liver, kidney, pancreas, and gut and are critical to the regulation
      of glucose homeostasis. Mutations of the HNF1alpha gene underlie maturity onset
      diabetes of the young (MODY3) in humans. DCoH acts as a cofactor for HNF1 that
      stabilizes the dimeric HNF1 complex. DCoH also catalyzes the recycling of
      tetrahydrobiopterin, a cofactor of aromatic amino acid hydroxylases. To examine
      the roles of DCoH, a targeted deletion allele of the murine DCoH gene was
      created. Mice lacking DCoH are viable and fertile but display
      hyperphenylalaninemia and a predisposition to cataract formation. Surprisingly,
      HNF1 function in DCoH null mice is only slightly impaired, and mice are mildly
      glucose-intolerant in contrast to HNF1alpha null mice, which are diabetic. DCoH
      function as it pertains to HNF1 activity appears to be partially complemented by
      a newly identified homolog, DCoH2.

PMID- 12011082
TI  - Effects of glucose, exogenous insulin, and carbachol on C-peptide and insulin
      secretion from isolated perifused rat islets.
AB  - Isolated perifused rat islets were stimulated with glucose, exogenous insulin, or
      carbachol. C-peptide and, where possible, insulin secretory rates were measured.
      Glucose (8-10 mm) induced dose-dependent and kinetically similar patterns of C
      peptide and insulin secretion. The addition of 100 nm bovine insulin had no
      effect on C-peptide release in response to 8-10 mm glucose stimulation. The
      addition of 100 nm bovine insulin or 500 nm human insulin together with 3 mm
      glucose had no stimulatory effect on C-peptide secretion rates from perifused rat
      islets. Stimulation with carbachol plus 7 mm glucose enhanced both C-peptide and
      insulin secretion, and the further addition of 100 nm bovine insulin had no
      inhibitory effect on C-peptide secretory rates under this condition. Perifusion
      studies using pharmacologic inhibitors (genistein and wortmannin) of the kinases
      thought to be involved in insulin signaling potentiated 10 mm glucose-induced
      secretion. The results support the following conclusions. 1) C-peptide release
      rates accurately reflect insulin secretion rates from collagenase-isolated,
      perifused rat islets. 2) Exogenously added bovine insulin exerts no inhibitory
      effect on release to several agonists including glucose. 3) In the presence of 3
      mm glucose, exogenously added bovine or human insulin do not stimulate endogenous
      insulin secretion.

PMID- 12011083
TI  - Differences in the regulation of the classical and the alternative pathway for
      bile acid synthesis in human liver. No coordinate regulation of CYP7A1 and
      CYP27A1.
AB  - It has been reported that there is a coordinate regulation of sterol 27
      hydroxylase (CYP27A1) and cholesterol 7alpha-hydroxylase (CYP7A1) in rats. Thus,
      the levels of the mRNA corresponding to these two enzymes were found to change in
      the same direction in rat liver and in isolated rat hepatocytes. In contrast,
      other groups have not seen such regulation of CYP27A1 in rabbit liver or in rat
      liver when using an activity assay. In the present work, the effect of bile acid
      treatment on human CYP27A1/luciferase reporter activity was studied in a
      transient transfection assay in human liver-derived HepG2 cells. Neither the
      endogenous 27-hydroxylase activity nor the CYP27A1/luciferase reporter activity
      were down-regulated by treatment of HepG2 cells with chenodeoxycholic acid or
      taurochenodeoxycholic acid. We also measured CYP27A1 mRNA and CYP7A1 mRNA in
      liver of humans subjected to treatment with chenodeoxycholic acid,
      ursodeoxycholic acid, hydroxymethylglutaryl (HMG)-CoA reductase inhibitor and a
      combination of HMG-CoA reductase inhibitor and cholestyramine. There was a 60
      fold variation in the levels of CYP7A1 mRNA but only a 5-fold variation in the
      levels of CYP27A1 mRNA. There was no correlation between the two mRNA species. It
      is concluded that, in humans, there is little or no coordinate regulation of
      CYP7A1 and CYP27A1 at the transcriptional level, and that CYP27A1 is not subject
      to a negative feedback control by bile acids. The results underline that marked
      species differences may exist in mechanisms for control of synthesis of bile
      acids and cholesterol homeostasis.

PMID- 12011084
TI  - Crystal structures of inhibitor complexes reveal an alternate binding mode in
      orotidine-5'-monophosphate decarboxylase.
AB  - The crystal structures of the enzyme orotidine-5'-monophosphate decarboxylase
      from Methanobacterium thermoautotrophicum complexed with its product UMP and the
      inhibitors 6-hydroxyuridine 5'-phosphate (BMP), XMP, and CMP are reported. A
      mutant version of the protein, in which four residues of the flexible phosphate
      binding loop (180)Gly-Gly(190) were removed and Arg(203) was replaced by alanine,
      was also analyzed. The XMP and CMP complexes reveal a ligand-binding mode that is
      distinct from the one identified previously with the aromatic rings located
      outside the binding pocket. A potential pathway for ligand binding is discussed.

PMID- 12011085
TI  - Toxoplasma gondii microneme secretion involves intracellular Ca(2+) release from
      inositol 1,4,5-triphosphate (IP(3))/ryanodine-sensitive stores.
AB  - Calcium-mediated microneme secretion in Toxoplasma gondii is stimulated by
      contact with host cells, resulting in the discharge of adhesins that mediate
      attachment. The intracellular source of calcium and the signaling pathway(s)
      triggering release have not been characterized, prompting our search for
      mediators of calcium signaling and microneme secretion in T. gondii. We
      identified two stimuli of microneme secretion, ryanodine and caffeine, which
      enhanced release of calcium from parasite intracellular stores. Ethanol, a
      previously characterized trigger of microneme secretion, stimulated an increase
      in parasite inositol 1,4,5-triphosphate, implying that this second messenger may
      mediate intracellular calcium release. Consistent with this observation,
      xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, inhibited
      microneme secretion and blocked parasite attachment and invasion of host cells.
      Collectively, these results suggest that T. gondii possess an intracellular
      calcium release channel with properties of the inositol 1,4,5
      triphosphate/ryanodine receptor superfamily. Intracellular calcium channels,
      previously studied almost exclusively in multicellular animals, appear to also be
      critical to the control of parasite calcium during the initial steps of host cell
      entry.

PMID- 12011086
TI  - Is the glycolytic flux in Lactococcus lactis primarily controlled by the redox
      charge? Kinetics of NAD(+) and NADH pools determined in vivo by 13C NMR.
AB  - The involvement of nicotinamide adenine nucleotides (NAD(+), NADH) in the
      regulation of glycolysis in Lactococcus lactis was investigated by using (13)C
      and (31)P NMR to monitor in vivo the kinetics of the pools of NAD(+), NADH, ATP,
      inorganic phosphate (P(i)), glycolytic intermediates, and end products derived
      from a pulse of glucose. Nicotinic acid specifically labeled on carbon 5 was
      synthesized and used in the growth medium as a precursor of pyridine nucleotides
      to allow for in vivo detection of (13)C-labeled NAD(+) and NADH. The capacity of
      L. lactis MG1363 to regenerate NAD(+) was manipulated either by turning on NADH
      oxidase activity or by knocking out the gene encoding lactate dehydrogenase
      (LDH). An LDH(-) deficient strain was constructed by double crossover. Upon
      supply of glucose, NAD(+) was constant and maximal (approximately 5 mm) in the
      parent strain (MG1363) but decreased abruptly in the LDH(-) strain both under
      aerobic and anaerobic conditions. NADH in MG1363 was always below the detection
      limit as long as glucose was available. The rate of glucose consumption under
      anaerobic conditions was 7-fold lower in the LDH(-) strain and NADH reached high
      levels (2.5 mm), reflecting severe limitation in regenerating NAD(+). However,
      under aerobic conditions the glycolytic flux was nearly as high as in MG1363
      despite the accumulation of NADH up to 1.5 mm. Glyceraldehyde-3-phosphate
      dehydrogenase was able to support a high flux even in the presence of NADH
      concentrations much higher than those of the parent strain. We interpret the data
      as showing that the glycolytic flux in wild type L. lactis is not primarily
      controlled at the level of glyceraldehyde-3-phosphate dehydrogenase by NADH. The
      ATP/ADP/P(i) content could play an important role.

PMID- 12011087
TI  - Mucus secretion from single submucosal glands of pig. Stimulation by carbachol
      and vasoactive intestinal peptide.
AB  - Secretion rates of >700 individual glands in isolated tracheal mucosa from 56
      adult pigs were monitored optically. "Basal" secretion of 0.7 +/- 0.1 nl x min(
      1) gland(-1) was observed 1-9 h post-harvest but was near zero on day 2.
      Secretion to carbachol (10 microm) peaked at 2-3 min and then declined to a
      sustained phase. Peak secretion was 12.4 +/- 1.1 nl x min(-1) gland(-1);
      sustained secretion was approximately one-third of peak secretion. Thapsigargin
      (1 microm) increased secretion from 0.1 +/- 0.05 to 0.7 +/- 0.2 nl x min(-1)
      gland(-1); thapsigargin did not cause contraction of the trachealis muscles.
      Isoproterenol and phenylephrine (10 microm each) were ineffective, but vasoactive
      intestinal peptide (1 microm) and forskolin (10 microm) each produced sustained
      secretion of 1.0 +/- 0.5 and 1.7 +/- 0.2 nl x min(-1) gland(-1), respectively.
      The density of actively secreting glands was 1.3/mm(2). Secretion to either
      carbachol or forskolin was inhibited (approximately 50%) by either bumetanide or
      HCO(3)(-) removal and inhibited approximately 90% by the combined treatments.
      Mucus secreted in response to carbachol or forskolin was acidic by approximately
      0.2 pH units relative to the bath and remained acidic by approximately 0.1 pH
      units after bumetanide. The strong secretory response to vasoactive intestinal
      peptide, the acidity of [cAMP](i)-stimulated mucus, and its inhibition by
      bumetanide were unexpected.

PMID- 12011088
TI  - Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif
      within the 3'-untranslated region of the androgen receptor messenger RNA.
AB  - The androgen receptor (AR) mediates androgen action and plays a central role in
      the proliferation of specific cancer cells. We demonstrated recently that AR mRNA
      stability is a major determinant of AR gene expression in prostate and breast
      cancer cells and that androgens differentially regulate AR mRNA decay dependent
      on cell type (Yeap, B. B., Kreuger, R. G., Leedman, P. J. (1999) Endocrinology
      140, 3282-3291). Here, we have identified a highly conserved UC-rich region in
      the 3-untranslated region of AR mRNA that contains a 5'-C(U)(n)C motif and a 3'
      CCCUCCC poly(C)-binding protein motif. In transfection studies with LNCaP human
      prostate cancer cells, the AR UC-rich region reduced expression of a luciferase
      reporter gene. The AR UC-rich region was a target for cytoplasmic and nuclear RNA
      binding proteins from human prostate and breast cancer cells as well as human
      testicular and breast cancer tissue. One of these proteins is HuR, a ubiquitously
      expressed member of the Elav/Hu family of RNA-binding proteins involved in the
      stabilization of several mRNAs. Poly(C)-binding protein-1 and -2 (CP1 and CP2),
      previously implicated in the control of mRNA turnover and translation, also bound
      avidly to the UC-rich region. Mutational analysis of the UC-rich region
      identified specific binding motifs for both HuR and the CPs. HuR and CP1 bound
      simultaneously to the UC-rich RNA and in a cooperative manner.
      Immunoprecipitation studies confirmed that each of these proteins associated with
      AR mRNA in prostate cancer cells. In summary, we have identified and
      characterized a novel complex of AR mRNA-binding proteins that target the highly
      conserved UC-rich region. The binding of HuR, CP1, and CP2 to AR mRNA suggests a
      role for each of these proteins in the post-transcriptional regulation of AR
      expression in cancer cells.

PMID- 12011089
TI  - Solution structure of plant nonspecific lipid transfer protein-2 from rice (Oryza
      sativa).
AB  - The three-dimensional structure of rice nonspecific lipid transfer protein
      (nsLTP2) has been solved for the first time. The structure of nsLTP2 was obtained
      using 813 distance constraints, 30 hydrogen bond constraints, and 19 dihedral
      angle constraints. Fifteen of the 50 random simulated annealing structures
      satisfied all of the constraints and possessed good nonbonded contacts. The novel
      three-dimensional fold of rice nsLTP2 contains a triangular hydrophobic cavity
      formed by three prominent helices. The four disulfide bonds required for
      stabilization of the nsLTP2 structure show a different pattern of cysteine
      pairing compared with nsLTP1. The C terminus of the protein is very flexible and
      forms a cap over the hydrophobic cavity. Molecular modeling studies suggested
      that the hydrophobic cavity could accommodate large molecules with rigid
      structures, such as sterols. The positively charged residues on the molecular
      surface of nsLTP2 are structurally similar to other plant defense proteins.

PMID- 12011090
TI  - Inactivation of Mre11 does not affect VSG gene duplication mediated by homologous
      recombination in Trypanosoma brucei.
AB  - We demonstrate, by gene deletion analysis, that Mre11 has a critical role in
      maintaining genomic integrity in Trypanosoma brucei. mre11(-/-) null mutant
      strains exhibited retarded growth but no delay or disruption of cell cycle
      progression. They showed also a weak hyporecombination phenotype and the
      accumulation of gross chromosomal rearrangements, which did not involve sequence
      translocation, telomere loss, or formation of new telomeres. The trypanosome
      mre11(-/-) strains were hypersensitive to phleomycin, a mutagen causing DNA
      double strand breaks (DSBs) but, in contrast to mre11(-/-) null mutants in other
      organisms and T. brucei rad51(-/-) null mutants, displayed no hypersensitivity to
      methyl methanesulfonate, which causes point mutations and DSBs. Mre11 therefore
      is important for the repair of chromosomal damage and DSBs in trypanosomes,
      although in this organism the intersection of repair pathways appears to differ
      from that in other organisms. Mre11 inactivation appears not to affect VSG gene
      switching during antigenic variation of a laboratory strain, which is perhaps
      surprising given the importance of homologous recombination during this process.

PMID- 12011091
TI  - RU486-induced glucocorticoid receptor agonism is controlled by the receptor N
      terminus and by corepressor binding.
AB  - Glucocorticoid-induced gene transcription has been shown to be mediated by
      coactivators bound to the glucocorticoid receptor (GR). The glucocorticoid
      antagonist RU486 interferes with the steroid-mediated activation and can also
      exhibit partial agonist activity, a response in which corepressors have been
      implicated. Here we have shown that deletion of the N terminus of GR totally
      abolishes the agonist activity of RU486. Furthermore, we have demonstrated that
      corepressors bind directly to the RU486-bound GR as determined by glutathione S
      transferase pull-down, mammalian two-hybrid assay, and coimmunoprecipitation.
      Fine mapping of the interaction regions within GR and the corepressor NCoR
      reveals a complex interaction profile that involves a number of domains in each
      protein. Notably, the N and the C termini of GR are both involved in corepressor
      binding. Thus, the N terminus of GR is a major determinant for RU486-dependent
      NCoR interaction as well as for RU486-mediated agonist activity.

PMID- 12011092
TI  - Lysine scanning mutagenesis delineates structural model of the nicotinic receptor
      ligand binding domain.
AB  - Nicotinic acetylcholine receptors (AChR) and their relatives mediate rapid
      chemical transmission throughout the nervous system, yet their atomic structures
      remain elusive. Here we use lysine scanning mutagenesis to determine the
      orientation of residue side chains toward core hydrophobic or surface hydrophilic
      environments and use this information to build a structural model of the ligand
      binding region of the AChR from adult human muscle. The resulting side-chain
      orientations allow assignment of residue equivalence between AChR subunits and an
      acetylcholine binding protein solved by x-ray crystallography, providing the
      foundation for homology modeling. The resulting structural model of the AChR
      provides a picture of the ACh binding site and predicts novel pairs of residues
      that stabilize subunit interfaces. The overall results suggest that lysine
      scanning can provide the basis for structural modeling of other members of the
      AChR superfamily as well as of other proteins with repeating structures
      delimiting a hydrophobic core.

PMID- 12011093
TI  - A mosquito salivary protein inhibits activation of the plasma contact system by
      binding to factor XII and high molecular weight kininogen.
AB  - The salivary glands of female mosquitoes contain a variety of bioactive
      substances that assist their blood-feeding behavior. Here, we report a salivary
      protein of the malarial vector mosquito, Anopheles stephensi, that inhibits
      activation of the plasma contact system. This factor, named hamadarin, is a 16
      kDa protein and a major component of the saliva of this mosquito. Assays using
      human plasma showed that hamadarin dose-dependently inhibits activation of the
      plasma contact system and subsequent release of bradykinin, a primary mediator of
      inflammatory reactions. Reconstitution experiments showed that hamadarin inhibits
      activation of the plasma contact system by inhibition of the reciprocal
      activation of factor XII and kallikrein. Direct binding assays demonstrated that
      this inhibitory effect is due to hamadarin binding to both factor XII and high
      molecular weight kininogen and interference in their association with the
      activating surface. The assays also showed that hamadarin binding to these
      proteins depends on Zn(2+) ions, suggesting that hamadarin binds to these contact
      factors by recognizing their conformational change induced by Zn(2+) binding. We
      propose that hamadarin may attenuate the host's acute inflammatory responses to
      the mosquito's bites by inhibition of bradykinin release and thus enable
      mosquitoes to take a blood meal efficiently and safely.

PMID- 12011094
TI  - Natural trans-spliced mRNAs are generated from the human estrogen receptor-alpha
      (hER alpha) gene.
AB  - The human estrogen receptor-alpha (hER alpha) gene is a complex genomic unit
      exhibiting alternative splicing and promoter usage in a tissue-specific manner.
      During the investigation of new hER alpha mRNA variants by rapid amplification of
      5' cDNA ends, we identified a cDNA in which the acceptor site of exon 1A, into
      which the different leader exons are normally alternatively spliced, was spliced
      accurately the 3' extremity of exon 1A (scrambled 1A-->1A hER alpha cDNA).
      Reverse transcription-PCR and S1 nuclease mapping analysis revealed that 1A-->1A
      hER alpha transcripts were not circular RNAs constituted by exon 1A only but
      corresponded to linear polyadenylated hER alpha RNAs composed of the eight coding
      exons of the hER alpha gene and characterized by a duplication of exon 1A.
      Genomic Southern blot experiments excluded the hypothesis of duplication of hER
      alpha exon 1A in the human genome. Therefore, these data suggested that 1A-->1A
      hER alpha transcripts were likely generated by trans-splicing. The production of
      such transcripts by trans-splicing of pre-mRNAs generated from a chimeric gene
      formed by a single hER alpha exon 1A, exon 2, and their flanking intronic regions
      was demonstrated in transient transfection experiments. Therefore, in addition to
      the alternative cis-splicing, the hER alpha gene is also subject to natural trans
      splicing.

PMID- 12011095
TI  - EDD, the human hyperplastic discs protein, has a role in progesterone receptor
      coactivation and potential involvement in DNA damage response.
AB  - The ubiquitin-protein ligase EDD encodes an orthologue of the hyperplastic discs
      tumor suppressor gene, which has a critical role in Drosophila development.
      Frequent allelic imbalance at the EDD chromosomal locus in human cancers suggests
      a role in tumorigenesis. In addition to a HECT (homologous to E6-AP carboxyl
      terminus) domain, the EDD protein contains a UBR1 zinc finger motif and ubiquitin
      associated domain, each of which indicates involvement in ubiquitinylation
      pathways. This study shows that EDD interacts with importin alpha 5 through
      consensus basic nuclear localization signals and is localized in cell nuclei. EDD
      also binds progesterone receptor (PR) and potentiates progestin-mediated gene
      transactivation. This activity is comparable with that of the coactivator SRC-1,
      but, in contrast, the interaction between EDD and PR does not appear to involve
      an LXXLL receptor-binding motif. EDD also binds calcium- and integrin-binding
      protein/DNA-dependent protein kinase-interacting protein, a potential target of
      ubiquitin-mediated proteolysis, and an altered association is found between EDD
      and calcium- and integrin-binding protein/DNA-dependent protein kinase
      interacting protein in response to DNA damage. The data presented here
      demonstrate a role for EDD in PR signaling but also suggest a link to cancer
      through DNA damage response pathways.

PMID- 12011096
TI  - NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through
      a phosphatidylinositol 4-kinase-dependent pathway.
AB  - Expression of NCS-1 (neuronal calcium sensor-1, also termed frequenin) in 3T3L1
      adipocytes strongly inhibited insulin-stimulated translocation of GLUT4 and
      insulin-responsive aminopeptidase. The effect of NCS-1 was specific for GLUT4 and
      the insulin-responsive aminopeptidase translocation as there was no effect on the
      trafficking of the cation-independent mannose 6-phosphate receptor or the GLUT1
      glucose transporter isoform. Moreover, NCS-1 showed partial colocalization with
      GLUT4-EGFP in the perinuclear region. The inhibitory action of NCS-1 was
      independent of calcium sequestration since neither treatment with ionomycin nor
      endothelin-1, both of which elevated the intracellular calcium concentration,
      restored insulin-stimulated GLUT4 translocation. Furthermore, NCS-1 did not alter
      the insulin-stimulated protein kinase B (PKB/Akt) phosphorylation or the
      recruitment of Cbl to the plasma membrane. In contrast, expression of the NCS-1
      effector phosphatidylinositol 4-kinase (PI 4-kinase) inhibited insulin-stimulated
      GLUT4 translocation, whereas co-transfection with an inactive PI 4-kinase mutant
      prevented the NCS-1-induced inhibition. These data demonstrate that PI 4-kinase
      functions to negatively regulate GLUT4 translocation through its interaction with
      NCS-1.

PMID- 12011097
TI  - Early growth response factor-1 is a critical transcriptional mediator of
      peroxisome proliferator-activated receptor-gamma 1 gene expression in human
      aortic smooth muscle cells.
AB  - To explore the molecular mechanisms of PPARgamma1 gene expression in vascular
      smooth muscle cells (VSMC), we hypothesized that early growth-response factor-1
      (Egr-1) might be a transcriptional mediator of the growth factor- and cytokine
      induced PPARgamma1 gene expression since a putative Egr-1 binding element was
      found in the human PPARgamma1 promoter. In this study, we document that
      overexpression of Egr-1 activates the human PPARgamma1 promoter in both VSMC and
      HepG2 cells. Using Northern blot analysis, we observed that growth factors and
      cytokines such as PDGF, bFGF, Ang II, TNFalpha, and IL-1beta induce Egr-1
      expression prior to PPARgamma1 up-regulation in human VSMC. In addition,
      overexpression of a constitutively active form of Egr-1 by adenoviral gene
      transfer in VSMC dramatically induced PPARgamma1 gene expression by 6-8-fold, and
      overexpression of NAB2, a potent negative feedback regulator of Egr-1, abrogated
      the growth factor- and cytokine-induced PPARgamma1 expression in VSMC.
      Furthermore, we demonstrate with gel mobility shift and transient transfection
      assays that the putative Egr-1 element in the human PPARgamma1 promoter
      specifically binds Egr-1 protein and becomes trans-activated by Egr-1. Taken
      together, our data demonstrate for the first time that Egr-1 is necessary and
      sufficient to activate human PPARgamma1 gene expression in VSMC.

PMID- 12011098
TI  - Impaired organic anion transport in kidney and choroid plexus of organic anion
      transporter 3 (Oat3 (Slc22a8)) knockout mice.
AB  - To begin to develop in vivo model systems for the assessment of the contributions
      of specific organic anion transporter (OAT) family members to detoxification,
      development, and disease, we carried out a targeted disruption of the murine
      organic anion transporter 3 (Oat3) gene. Surviving Oat3(-/-) animals appear
      healthy, are fertile, and do not exhibit any gross morphological tissue
      abnormalities. No Oat3 mRNA expression was detected in kidney, liver, or choroid
      plexus (CP) of Oat3(-/-) mice. A distinct phenotype manifested by a substantial
      loss of organic anion transport capacity in kidney and CP was identified. Uptake
      sensitive to inhibition by bromosulfophthalein or probenecid was observed for
      taurocholate, estrone sulfate, and para-aminohippurate in renal slices from wild
      type mice, whereas in Oat3(-/-) animals transport of these substances was greatly
      reduced. No discernable differences in uptake were observed between hepatic
      slices from wild-type and Oat3(-/-) littermates, suggesting Oat3 does not play a
      major role in hepatic organic anion uptake. Cellular accumulation of fluorescein
      was reduced by approximately 75% in CP from Oat3(-/-) mice. However, capillary
      accumulation of fluorescein-methotrexate was unchanged, indicating the effects of
      Oat3 loss are restricted to the entry step and that Oat3 is localized to the
      apical membrane of CP. These data indicate a key role for Oat3 in systemic
      detoxification and in control of the organic anion distribution in cerebrospinal
      fluid.

PMID- 12011099
TI  - Molecular basis defining human Chlamydia trachomatis tissue tropism. A possible
      role for tryptophan synthase.
AB  - Here we report the cloning and sequencing of a region of the chlamydiae
      chromosome termed the "plasticity zone" from all the human serovars of C.
      trachomatis containing the tryptophan biosynthesis genes. Our results show that
      this region contains orthologues of the tryptophan repressor as well as the alpha
      and beta subunits of tryptophan synthase. Results from reverse transcription-PCR
      and Western blot analyses indicate that the trpBA genes are transcribed, and
      protein products are expressed. The TrpB sequences from all serovars are highly
      conserved. In comparison with other tryptophan synthase beta subunits, the
      chlamydial TrpB subunit retains all conserved amino acid residues required for
      beta reaction activity. In contrast, the chlamydial TrpA sequences display
      numerous mutations, which distinguish them from TrpA sequences of all other
      prokaryotes. All ocular serovars contain a deletion mutation resulting in a
      truncated TrpA protein, which lacks alpha reaction activity. The TrpA protein
      from the genital serovars retains conserved amino acids required for catalysis
      but has mutated several active site residues involved in substrate binding.
      Complementation analysis in Escherichia coli strains, with defined mutations in
      tryptophan biosynthesis, and in vitro enzyme activity data, with cloned TrpB and
      TrpA proteins, indicate these mutations result in a TrpA protein that is unable
      to utilize indole glycerol 3-phosphate as substrate. In contrast, the chlamydial
      TrpB protein can carry out the beta reaction, which catalyzes the formation of
      tryptophan from indole and serine. The activity of the chlamydial Trp B protein
      differs from that of the well characterized E. coli and Salmonella TrpBs in
      displaying an absolute requirement for full-length TrpA. Taken together our data
      indicate that genital, but not ocular, serovars are capable of utilizing
      exogenous indole for the biosynthesis of tryptophan.

PMID- 12011100
TI  - m-Bop, a repressor protein essential for cardiogenesis, interacts with skNAC, a
      heart- and muscle-specific transcription factor.
AB  - The m-Bop protein encoded by the mouse Bop gene is strongly expressed in heart
      and skeletal muscle, and recent studies with Bop knockout mice have demonstrated
      that m-Bop is essential for cardiogenesis in vivo and can act as a HDAC-dependent
      repressor in vitro. In the present studies, m-Bop was observed to interact with
      skNAC, a reported transcriptional activator specific to heart and skeletal
      muscle. The amino-terminal S region of the split S-ET domain of m-Bop as well as
      the MYND domain were required for interaction with skNAC in both the two-hybrid
      system and in coimmunoprecipitation experiments from cultured mammalian cells. As
      shown previously for interaction of the MYND domain-containing transcriptional
      corepressor, BS69, with several viral and cellular oncoproteins, a PXLXP motif in
      skNAC was required for interaction with m-Bop. Similar kinetics of induction and
      localization of m-Bop and skNAC during the induction of myogenesis in cultured
      C2C12 cells suggests a possible associated role for these proteins during this
      process.

PMID- 12011101
TI  - Combinatorial ganglioside biosynthesis.

PMID- 12011102
TI  - Sphingosine 1-phosphate, a key cell signaling molecule.

PMID- 12011103
TI  - The Ceramide-centric universe of lipid-mediated cell regulation: stress
      encounters of the lipid kind.

PMID- 12011104
TI  - De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway.

PMID- 12011105
TI  - Sphingolipid transport: rafts and translocators.

PMID- 12011106
TI  - Searching for the middle ground: mechanisms of chromosome alignment during
      mitosis.
AB  - The contributions of key molecules predicted to align chromosomes at the center
      of the mitotic spindle have been recently examined. New results dictate that
      models for how chromosomes align during the early stages of mitosis must be
      revised to integrate properties of microtubule-based motor proteins as well as
      microtubule dynamics.

PMID- 12011107
TI  - Secretory traffic in the eukaryotic parasite Toxoplasma gondii: less is more.
AB  - Name a single-celled eukaryote that boasts a small genome size, is easily
      cultivated in haploid form, for which a wide variety of molecular genetic tools
      are available, and that exhibits a simple, polarized secretory apparatus with a
      well-defined endoplasmic reticulum and Golgi that can serve as a model for
      understanding secretion. Got it? Now name a cell with all these attributes that
      contains at least a dozen distinct and morphologically well-defined intracellular
      organelles, including three distinct types of secretory vesicles and two
      endosymbiotic organelles. Not so sure anymore?

PMID- 12011108
TI  - The p75 receptor transduces the signal from myelin-associated glycoprotein to
      Rho.
AB  - Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth
      from a variety of neurons. The receptor for MAG or signals that elicit
      morphological changes in neurons remained to be established. Here we show that
      the neurotrophin receptor p75 (p75(NTR)) is the signal transducing element for
      MAG. Adult dorsal root ganglion neurons or postnatal cerebellar neurons from mice
      carrying a mutation in the p75(NTR) gene are insensitive to MAG with regard to
      neurite outgrowth. MAG activates small GTPase RhoA, leading to retarded outgrowth
      when p75(NTR)) is present. Colocalization of p75(NTR) and MAG binding is seen in
      neurons. Ganglioside GT1b, which is one of the binding partners of MAG,
      specifically associates with p75(NTR). Thus, p75(NTR) and GT1b may form a
      receptor complex for MAG to transmit the inhibitory signals in neurons.

PMID- 12011109
TI  - The kinetically dominant assembly pathway for centrosomal asters in
      Caenorhabditis elegans is gamma-tubulin dependent.
AB  - gamma-Tubulin-containing complexes are thought to nucleate and anchor centrosomal
      microtubules (MTs). Surprisingly, a recent study (Strome, S., J. Powers, M. Dunn,
      K. Reese, C.J. Malone, J. White, G. Seydoux, and W. Saxton. Mol. Biol. Cell.
      12:1751-1764) showed that centrosomal asters form in Caenorhabditis elegans
      embryos depleted of gamma-tubulin by RNA-mediated interference (RNAi). Here, we
      investigate the nucleation and organization of centrosomal MT asters in C.
      elegans embryos severely compromised for gamma-tubulin function. We characterize
      embryos depleted of approximately 98% centrosomal gamma-tubulin by RNAi, embryos
      expressing a mutant form of gamma-tubulin, and embryos depleted of a gamma
      tubulin-associated protein, CeGrip-1. In all cases, centrosomal asters fail to
      form during interphase but assemble as embryos enter mitosis. The formation of
      these mitotic asters does not require ZYG-9, a centrosomal MT-associated protein,
      or cytoplasmic dynein, a minus end-directed motor that contributes to self
      organization of mitotic asters in other organisms. By kinetically monitoring MT
      regrowth from cold-treated mitotic centrosomes in vivo, we show that centrosomal
      nucleating activity is severely compromised by gamma-tubulin depletion. Thus,
      although unknown mechanisms can support partial assembly of mitotic centrosomal
      asters, gamma-tubulin is the kinetically dominant centrosomal MT nucleator.

PMID- 12011110
TI  - Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing
      protein (MISS), a new MAPK substrate.
AB  - Vertebrate oocytes arrest in the second metaphase of meiosis (metaphase II [MII])
      by an activity called cytostatic factor (CSF), with aligned chromosomes and
      stable spindles. Segregation of chromosomes occurs after fertilization. The
      Mos/.../MAPK (mitogen-activated protein kinases) pathway mediates this MII
      arrest. Using a two-hybrid screen, we identified a new MAPK partner from a mouse
      oocyte cDNA library. This protein is unstable during the first meiotic division
      and accumulates only in MII, where it localizes to the spindle. It is a substrate
      of the Mos/.../MAPK pathway. The depletion of endogenous RNA coding for this
      protein by three different means (antisense RNA, double-stranded [ds] RNA, or
      morpholino oligonucleotides) induces severe spindle defects specific to MII
      oocytes. Overexpressing the protein from an RNA not targeted by the morpholino
      rescues spindle destabilization. However, dsRNA has no effect on the first two
      mitotic divisions. We therefore have discovered a new MAPK substrate involved in
      maintaining spindle integrity during the CSF arrest of mouse oocytes, called MISS
      (for MAP kinase-interacting and spindle-stabilizing protein).

PMID- 12011111
TI  - In vivo analysis of NHPX reveals a novel nucleolar localization pathway involving
      a transient accumulation in splicing speckles.
AB  - The NHPX protein is a nucleolar factor that binds directly to a conserved RNA
      target sequence found in nucleolar box C/D snoRNAs and in U4 snRNA. Using
      enhanced yellow fluorescent protein (EYFP)- and enhanced cyan fluorescent protein
      NHPX fusions, we show here that NHPX is specifically accumulated in both nucleoli
      and Cajal bodies (CBs) in vivo. The fusion proteins display identical
      localization patterns and RNA binding specificities to the endogenous NHPX.
      Analysis of a HeLa cell line stably expressing EYFP-NHPX showed that the
      nucleolar accumulation of NHPX was preceded by its transient accumulation in
      splicing speckles. Only newly expressed NHPX accumulated in speckles, and the
      nucleolar pool of NHPX did not interchange with the pool in speckles, consistent
      with a unidirectional pathway. The transient accumulation of NHPX in speckles
      prior to nucleoli was observed in multiple cell lines, including primary cells
      that lack CBs. Inhibitor studies indicated that progression of newly expressed
      NHPX from speckles to nucleoli was dependent on RNA polymerase II transcription,
      but not on RNA polymerase I activity. The data show a specific temporal pathway
      involving the sequential and directed accumulation of NHPX in distinct subnuclear
      compartments, and define a novel mechanism for nucleolar localization.

PMID- 12011112
TI  - The Sec34/Sec35p complex, a Ypt1p effector required for retrograde intra-Golgi
      trafficking, interacts with Golgi SNAREs and COPI vesicle coat proteins.
AB  - The Sec34/35 complex was identified as one of the evolutionarily conserved
      protein complexes that regulates a cis-Golgi step in intracellular vesicular
      transport. We have identified three new proteins that associate with Sec35p and
      Sec34p in yeast cytosol. Mutations in these Sec34/35 complex subunits result in
      defects in basic Golgi functions, including glycosylation of secretory proteins,
      protein sorting, and retention of Golgi resident proteins. Furthermore, the
      Sec34/35 complex interacts genetically and physically with the Rab protein Ypt1p,
      intra-Golgi SNARE molecules, as well as with Golgi vesicle coat complex COPI. We
      propose that the Sec34/35 protein complex acts as a tether that connects cis
      Golgi membranes and COPI-coated, retrogradely targeted intra-Golgi vesicles.

PMID- 12011113
TI  - Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.
AB  - A central tenet of nerve growth factor (NGF) action that is poorly understood is
      its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is
      initiated at the nerve terminal and conveyed to the soma. We identified an NGF
      induced protein that we termed Pincher (pinocytic chaperone) that mediates
      endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells,
      overexpression of Pincher dramatically stimulated NGF-induced endocytosis of
      TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell
      surface ruffles. Subsequently, a system of Pincher-containing tubules mediated
      the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These
      vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated
      protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited
      the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated
      cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that
      Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA
      endosomes with persistent signaling potential.

PMID- 12011114
TI  - Myogenic cell proliferation and generation of a reversible tumorigenic phenotype
      are triggered by preirradiation of the recipient site.
AB  - Environmental influences have profound yet reversible effects on the behavior of
      resident cells. Earlier data have indicated that the amount of muscle formed from
      implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the
      host mouse muscle. Here we confirm this phenomenon, showing that it varies
      between host mouse strains. However, it is unclear whether it is due to secretion
      of proliferative factors or reduction of antiproliferative agents. To investigate
      this further, we have exploited the observation that the immortal myogenic C2 C12
      cell line forms tumors far more rapidly in irradiated than in nonirradiated host
      muscle. We show that the effect of preirradiation on tumor formation is
      persistent and dose dependent. However, C2 C12 cells are not irreversibly
      compelled to form undifferentiated tumor cells by the irradiated muscle
      environment and are still capable of forming large amounts of muscle when
      reimplanted into a nonirradiated muscle. In a clonal analysis of this effect, we
      discovered that C2 C12 cells have a bimodal propensity to form tumors; some
      clones form no tumors even after extensive periods in irradiated graft sites,
      whereas others rapidly form extensive tumors. This illustrates the subtle
      interplay between the phenotype of implanted cells and the factors in the muscle
      environment.

PMID- 12011115
TI  - Inducible dimerization of FGFR1: development of a mouse model to analyze
      progressive transformation of the mammary gland.
AB  - To develop an inducible and progressive model of mammary gland tumorigenesis,
      transgenic mice were generated with a mouse mammary tumor virus-long terminal
      repeat-driven, conditional, fibroblast growth factor (FGF)-independent FGF
      receptor (FGFR)1 (iFGFR1) that can be induced to dimerize with the drug AP20187.
      Treatment of transgenic mice with AP20187 resulted in iFGFR1 tyrosine
      phosphorylation, increased proliferation, activation of mitogen-activated protein
      kinase and Akt, and lateral budding. Lateral buds appeared as early as 3 d after
      AP20187 treatment and initially consisted of bilayered epithelial cells and
      displayed apical and basolateral polarity appeared after 13 d of AP20187
      treatment. Invasive lesions characterized by multicell-layered lateral buds,
      decreased myoepithelium, increased vascular branching, and loss of cell polarity
      were observed after 2-4 wk of treatment. These data indicate that acute iFGFR1
      signaling results in increased lateral budding of the mammary ductal epithelium,
      and that sustained activation induces alveolar hyperplasia and invasive lesions.

PMID- 12011117
TI  - Biochemotherapy for advanced melanoma: maybe it is real.

PMID- 12011116
TI  - Fibroblast growth factor-specific modulation of cellular response by syndecan-4.
AB  - Proteoglycans participate in growth factor interaction with the cell surface
      through their heparan sulfate chains (HS), but it is not known if they are
      otherwise involved in growth factor signaling. It appears now that the syndecan-4
      core protein, a transmembrane proteoglycan shown previously to bind
      phosphatidylinositol 4,5-bisphosphate (PIP(2)) and activate PKC alpha,
      participates in mediating the effects of fibroblast growth factor (FGF)2 on cell
      function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its
      affinity to PIP(2) (PIP(2)(-)) or disrupted its postsynaptic density 95, disk
      large, zona occludens-1 (PDZ)-dependent binding (PDZ(-)) produced a FGF2-specific
      dominant negative phenotype in endothelial cells as evidenced by the marked
      decline of their migration and proliferation rates and the impairment of their
      capacity to form tubes. In both cases, the molecular mechanism was determined to
      consist of a decrease in the syndecan-4-dependent activation of PKC alpha. This
      decrease was caused either by inhibition of FGF2-induced syndecan-4
      dephosphorylation in the case of the PDZ(-) mutation or by disruption of
      basolateral targeting of syndecan-4 and its associated PDZ-dependent complex in
      the case of the PIP(2)(-) mutation. These results suggest that PKCalpha
      activation and PDZ-mediated formation of a serine/threonine phosphatase
      containing complex by syndecan-4 are downstream events of FGF2 signaling.

PMID- 12011118
TI  - Treatment of myelodysplastic syndrome: questions raised by the azacitidine
      experience.

PMID- 12011119
TI  - High-throughput tissue microarray analysis used to evaluate biology and
      prognostic significance of the E-cadherin pathway in non-small-cell lung cancer.
AB  - PURPOSE: E-cadherin (E-cad) and its associated intracellular molecules, catenins,
      are critical for intercellular epithelial adhesion and are often expressed in non
      small-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to
      investigate the expression of cadherins and catenins and their prognostic
      significance in NSCLC. PATIENTS AND METHODS: Tumor tissue samples from 193
      patients with stages I to III NSCLC were obtained from the University of Colorado
      Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in
      triplicate for the TMAs, and slides were stained by immunohistochemistry with
      antibodies against E-cad, N-cadherin, alpha (alpha)-, beta (beta)-, and gamma
      (gamma)-catenin, p120, p27, and adenomatous polyposis coli (APC) gene product.
      Clinical data were collected by the tumor registries. Patients were followed for
      a median period of 51 months (range, 18 to 100 months). RESULTS: Absent or
      severely reduced membranous expression for E-cad, alpha-, beta-, and gamma
      catenin, and p120 were observed in 10%, 17%, 8%, 31%, and 61% of the cases,
      respectively. Tumor cell dedifferentiation correlated with reduced expression for
      E-cad, beta-catenin, gamma-catenin, and p120 in squamous cell carcinomas but not
      in adenocarcinomas. There was an inverse correlation between nodal metastasis and
      expression of E-cad and gamma-catenin. Besides the traditional clinical
      prognostic variables, E-cad and alpha-, beta-, and gamma-catenin expression were
      of positive prognostic value in univariate survival analyses. In multivariate
      analysis, E-cad expression was the only independent prognostic factor for
      survival in addition to age, node status, tumor status, and pathologic surgical
      margins. CONCLUSION: Reduced expression of E-cad and catenins is associated with
      tumor cell dedifferentiation, local invasion, regional metastasis, and reduced
      survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.

PMID- 12011120
TI  - Randomized controlled trial of azacitidine in patients with the myelodysplastic
      syndrome: a study of the cancer and leukemia group B.
AB  - PURPOSE: Patients with high-risk myelodysplastic syndrome (MDS) have high
      mortality from bone marrow failure or transformation to acute leukemia.
      Supportive care is standard therapy. We previously reported that azacitidine (Aza
      C) was active in patients with high-risk MDS. PATIENTS AND METHODS: A randomized
      controlled trial was undertaken in 191 patients with MDS to compare Aza C (75
      mg/m(2)/d subcutaneously for 7 days every 28 days) with supportive care. MDS was
      defined by French-American-British criteria. New rigorous response criteria were
      applied. Both arms received transfusions and antibiotics as required. Patients in
      the supportive care arm whose disease worsened were permitted to cross over to
      Aza C. RESULTS: Responses occurred in 60% of patients on the Aza C arm (7%
      complete response, 16% partial response, 37% improved) compared with 5%
      (improved) receiving supportive care (P <.001). Median time to leukemic
      transformation or death was 21 months for Aza C versus 13 months for supportive
      care (P =.007). Transformation to acute myelogenous leukemia occurred as the
      first event in 15% of patients on the Aza C arm and in 38% receiving supportive
      care (P =.001). Eliminating the confounding effect of early cross-over to Aza C,
      a landmark analysis after 6 months showed median survival of an additional 18
      months for Aza C and 11 months for supportive care (P =.03). Quality-of-life
      assessment found significant major advantages in physical function, symptoms, and
      psychological state for patients initially randomized to Aza C. CONCLUSION: Aza C
      treatment results in significantly higher response rates, improved quality of
      life, reduced risk of leukemic transformation, and improved survival compared
      with supportive care. Aza C provides a new treatment option that is superior to
      supportive care for patients with the MDS subtypes and specific entry criteria
      treated in this study.

PMID- 12011121
TI  - Impact of azacytidine on the quality of life of patients with myelodysplastic
      syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B
      study.
AB  - PURPOSE: The impact of azacytidine (Aza C) on the quality of life of 191 patients
      with myelodysplastic syndrome was assessed in a phase III Cancer and Leukemia
      Group B trial (9221). PATIENTS AND METHODS: One hundred ninety-one patients (mean
      age, 67.5 years; 69% male) were randomized to receive either Aza C (75 mg/m(2)
      subcutaneous for 7 days every 4 weeks) or supportive care, with supportive care
      patients crossing over to Aza C upon disease progression. Quality of life was
      assessed by centrally conducted telephone interviews at baseline and days 50,
      106, and 182. Overall quality of life, psychological state, and social
      functioning were assessed by the European Organization for Research and Treatment
      of Cancer (EORTC) Quality of Life Questionnaire C30 and the Mental Health
      Inventory (MHI). RESULTS: Patients on the Aza C arm experienced significantly
      greater improvement in fatigue (EORTC, P =.001), dyspnea (EORTC, P =.0014),
      physical functioning (EORTC, P =.0002), positive affect (MHI, P =.0077), and
      psychological distress (MHI, P =.015) over the course of the study period than
      those in the supportive care arm. Particularly striking were improvements in
      fatigue and psychological state (MHI) in patients treated with Aza C compared
      with those receiving supportive care for patients who remained on study through
      at least day 106, corresponding to four cycles of Aza C. Significant differences
      between the two groups in quality of life were maintained even after controlling
      for the number of RBC transfusions. CONCLUSION: Improved quality of life for
      patients treated with Aza C coupled with significantly greater treatment response
      and delayed time to transformation to acute myeloid leukemia or death compared
      with patients on supportive care (P <.001) establishes Aza C as an important
      treatment option for myelodysplastic syndrome.

PMID- 12011122
TI  - Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan
      radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or
      refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.
AB  - PURPOSE: Radioimmunotherapy combines biologic and radiolytic mechanisms to target
      and destroy tumor cells, thus offering a needed therapeutic alternative for
      refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study
      compares the novel radioimmunotherapy yttrium-90 ((90)Y) ibritumomab tiuxetan
      with a control immunotherapy, rituximab, in 143 patients with relapsed or
      refractory low-grade, follicular, or transformed CD20(+) transformed NHL.
      PATIENTS AND METHODS: Patients received either a single intravenous (IV) dose of
      (90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly
      for four doses (n = 70). The radioimmunotherapy group was pretreated with two
      rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium
      111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point,
      overall response rate (ORR), was assessed by an independent, blinded, lymphoma
      expert panel. RESULTS: ORR was 80% for the (90)Y ibritumomab tiuxetan group
      versus 56% for the rituximab group (P =.002). Complete response (CR) rates were
      30% and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups, respectively
      (P =.04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier
      estimated median duration of response was 14.2 months in the (90)Y ibritumomab
      tiuxetan group versus 12.1 months in the control group (P =.6), and time to
      progression was 11.2 versus 10.1 months (P =.173) in all patients. Durable
      responses of > or = 6 months were 64% versus 47% (P =.030). Reversible
      myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan.
      CONCLUSION: Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated
      and produces statistically and clinically significant higher ORR and CR compared
      with rituximab alone.

PMID- 12011123
TI  - Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic
      leukemia.
AB  - PURPOSE: To assess the efficacy and toxicity of a new treatment program of
      intensified and shortened cyclical chemotherapy (protocol 8707) in adults with
      acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Previously untreated
      adults < or = 60 years old with ALL were treated with a four-agent induction
      chemotherapy regimen. This was followed by cyclical postremission therapy with
      high-dose cytarabine/etoposide; high-dose methotrexate/6-mercaptopurine; and
      daunorubicin, vincristine, prednisone, and asparaginase. Maintenance chemotherapy
      with oral methotrexate and 6-mercaptopurine was continued for 30 months. CNS
      prophylaxis was given with intrathecal methotrexate in addition to the systemic
      chemotherapy indicated above. RESULTS: Seventy-eight of 84 patients (93%)
      achieved complete remission. With a median follow-up of 5.6 years, 5-year event
      free survival (EFS) of all remission patients is 52%. Patients with high-risk
      features including adverse cytogenetics, failure to achieve remission with the
      first cycle of chemotherapy, and B-precursor disease with WBC counts more than
      100,000/microL all relapsed unless taken off study for transplantation. For
      patients without these high-risk features, 5-year EFS was 60%. Compared with our
      previous treatment regimen, results appear to be improved for patients with
      standard-risk B-precursor disease (5-year EFS, 66% v 34%; P =.01). CONCLUSION:
      Intensified and shortened chemotherapy may improve the outcome for patients with
      ALL with B-precursor disease lacking high-risk features. Further trials of this
      regimen are warranted.

PMID- 12011125
TI  - Comparison of cytogenetic and molecular cytogenetic detection of chromosome
      abnormalities in 240 consecutive adult patients with acute myeloid leukemia.
AB  - PURPOSE: To prospectively compare cytogenetic and molecular cytogenetic analysis
      for the detection of the most relevant chromosome abnormalities in a large series
      of patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: Two hundred
      forty consecutive adult patients with AML entered onto the multicenter treatment
      trial AML HD93 were studied. Chromosome banding and fluorescence in situ
      hybridization (FISH) applying a comprehensive set of genomic DNA probes were
      performed in a single reference laboratory. RESULTS: Two cases of inv(16), three
      cases of t(11q23), and three cases of t(8;21)var were only detected by molecular
      cytogenetics. By FISH, aberrations were identified in three cases with normal
      karyotypes: inv(16), -Y (in a patient with low metaphase yield on chromosome
      banding) and a 12p microdeletion. Additional aneuploidies, in particular +8q and
      +11q, were diagnosed by FISH; however, virtually all these aberrations occurred
      in patients with complex karyotypes or as an additional abnormality in leukemias
      with an AML-specific translocation. Finally, aberrations were detected by FISH in
      eight of 14 patients with no assessable metaphases. CONCLUSION: In most cases of
      AML, conventional cytogenetic study reliably detects chromosomal abnormalities,
      and this method should not be replaced by FISH. FISH should be used as a
      complementary method for the detection of more subtle abnormalities, such as
      inv(16) and t(11q23), in all patients with newly diagnosed AML and for suspected
      t(8;21)var. Furthermore, molecular cytogenetics using this comprehensive set of
      DNA probes provides a valuable diagnostic tool for patients with poor chromosome
      morphology, low or no yields of metaphase cells, or both.

PMID- 12011124
TI  - Shortened first-line high-dose chemotherapy for patients with poor-prognosis
      aggressive lymphoma.
AB  - PURPOSE: Randomized trial LNH93-3 was conducted on patients who had poor
      prognosis aggressive lymphoma and were younger than 60 years with two to three
      factors of the age-adjusted International Prognostic Index to evaluate the
      benefit of early high-dose therapy (HDT) with autologous stem-cell
      transplantation (ASCT). PATIENTS AND METHODS: Patients were randomized between
      doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP)
      chemotherapy followed by sequential consolidation and an experimental shortened
      treatment consisting of three cycles with escalated doses of cyclophosphamide,
      epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral
      blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1
      nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT. RESULTS:
      Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP
      (181 patients) and HDT (189 patients), respective complete remission rates were
      64% and 63%. With a median follow-up of 60 months, 5-year overall survival and
      event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007)
      and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently
      affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009),
      bone marrow involvement (P =.003), and HDT treatment group (P =.04). CONCLUSION:
      Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy
      regimen. These results indicate that the received dose-intensity before HDT was
      too low when compared with ACVBP and HDT and was given too early.

PMID- 12011126
TI  - Randomized, double-blind, placebo-controlled trial of recombinant human
      erythropoietin, epoetin Beta, in hematologic malignancies.
AB  - PURPOSE: To investigate the effect of recombinant human erythropoietin (epoetin
      beta) on anemia, transfusion need, and quality of life (QOL) in severely anemic
      patients with low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic
      leukemia (CLL), or multiple myeloma (MM). PATIENTS AND METHODS: Transfusion
      dependent patients with NHL (n = 106), CLL (n = 126), or MM (n = 117) and a low
      serum erythropoietin concentration were randomized to receive epoetin beta 150
      IU/kg or placebo subcutaneously three times a week for 16 weeks. Primary efficacy
      criteria were transfusion-free and transfusion- and severe anemia-free survival
      (hemoglobin [Hb] > 8.5 g/dL) between weeks 5 to 16. Response was defined as an
      increase in Hb > or = 2 g/dL with elimination of transfusion need. QOL was
      assessed by the Functional Assessment of Cancer Therapy scale. RESULTS:
      Transfusion-free (P =.0012) survival and transfusion- and severe anemia-free
      survival (P =.0001) were significantly greater in the epoetin beta group versus
      placebo (Wald chi(2) test), giving a relative risk reduction of 43% and 51%,
      respectively. The response rate was 67% and 27% in the epoetin beta versus the
      placebo group, respectively (P <.0001). After 12 and 16 weeks of treatment, QOL
      significantly improved in the epoetin beta group compared with placebo (P <.05);
      this improvement correlated with an increase in Hb concentration (> or = 2 g/dL).
      A target Hb that could be generally recommended could not be identified.
      CONCLUSION: Many severely anemic and transfusion-dependent patients with advanced
      MM, NHL, and CLL and a low performance status benefited from epoetin therapy,
      with elimination of severe anemia and transfusion need, and improvement in QOL.

PMID- 12011127
TI  - Influence of unrecognized molecular heterogeneity on randomized clinical trials.
AB  - PURPOSE: In solid tumor oncology, decisions regarding treatment and eligibility
      for trials are governed by histologic diagnosis. Despite this reliance on
      histology and the assumption that histology defines the disease, underlying
      molecular heterogeneity likely differentiates among patients' outcomes. PATIENTS
      AND METHODS: To illustrate how unrecognized molecular heterogeneity might obscure
      a truly effective new therapy for cancer, we analyzed the planning assumptions
      and results of a hypothetical randomized controlled trial of chemoradiotherapy
      for a cancer found to be drug sensitive in preliminary phase II studies. RESULTS:
      Randomized controlled trials of effective cancer therapies can be falsely
      negative if therapeutic benefit is overestimated during study design because of
      enrichment of phase II trials for treatment-sensitive subtypes, a beneficial
      effect in responding patients is diluted by large numbers of nonresponding
      patients, or a beneficial effect in responders is reversed by a negative effect
      in nonresponders. CONCLUSION: Molecular heterogeneity, if it confers different
      risks to patients and is unaccounted for in the design of a randomized study, can
      result in a clinical trial that is underpowered and fails to detect a truly
      effective new therapy for cancer.

PMID- 12011128
TI  - Voice rehabilitation after total laryngectomy and postoperative radiation
      therapy.
AB  - PURPOSE: The purpose of this study was to evaluate voice rehabilitation after
      laryngectomy and postoperative irradiation for patients with squamous cell
      carcinoma of the larynx and hypopharynx. PATIENTS AND METHODS: Between December
      1983 and December 1998, 173 patients underwent a total laryngectomy and
      postoperative irradiation and had follow-up from 3 to 188 months (median, 38
      months). Three patients were lost to follow-up at 63, 39, and 4 months after
      treatment. All other living patients had follow-up for 2 years or longer. Twelve
      (7%) patients had incomplete data pertaining to voice rehabilitation. RESULTS:
      Data pertaining to voice rehabilitation were available at 2 to 3 years and longer
      and 5 years and longer after treatment for 118 and 69 patients, respectively. The
      methods of voice rehabilitation at 2 to 3 years and longer and 5 years and longer
      were as follows: tracheoesophageal, 27% and 19%; artificial larynx, 50% and 57%;
      esophageal, 1% and 3%; nonvocal, 17% and 14%; and no data, 5% and 7%,
      respectively. CONCLUSION: The most common form of voice rehabilitation after
      total laryngectomy and postoperative radiation therapy is the artificial larynx.
      Although the tracheoesophageal puncture is a technique frequently promoted by
      clinicians as a superior method, a relatively small subset of patients are
      successfully rehabilitated long-term. However, of those who undergo a
      tracheoesophageal puncture, approximately half will use this method of voice
      rehabilitation long term.

PMID- 12011129
TI  - Pregnancy outcome after treatment for Wilms tumor: a report from the National
      Wilms Tumor Study Group.
AB  - PURPOSE: This study was undertaken to determine the effect, if any, of prior
      treatment with radiation therapy or chemotherapy for Wilms tumor diagnosed during
      childhood or adolescence on live births, birthweight, and the frequency of
      congenital malformations. PATIENTS AND METHODS: We reviewed pregnancy outcomes
      among survivors of Wilms tumor treated with or without irradiation to the flank
      or tumor bed on National Wilms Tumor Studies 1, 2, 3, and 4 using a maternal
      questionnaire and review of both maternal and offspring medical records. RESULTS:
      We received reports regarding 427 pregnancies with duration of 20 weeks or
      longer, including 409 liveborn singletons for whom 309 sets of medical records
      were reviewed. Malposition of the fetus and early or threatened labor were more
      frequent among irradiated women. Both were more frequent among women who received
      higher radiation therapy doses. The offspring of the irradiated female patients
      were more likely to weigh less than 2,500 g at birth and to be of less than 36
      weeks gestation, with both being more frequent after higher doses of radiation.
      An increased percentage of offspring of irradiated females had one or more
      congenital malformations. CONCLUSION: Women who receive flank radiation therapy
      as part of their treatment for Wilms tumor are at increased risk of fetal
      malposition and premature labor. The offspring of these women are at risk for low
      birthweight, premature (< 36 weeks gestation) birth, and the occurrence of
      congenital malformations. These risks must be considered in the obstetrical
      management of female survivors of Wilms tumor.

PMID- 12011130
TI  - Self-rated health as a predictor of survival among patients with advanced cancer.
AB  - PURPOSE: Evidence is emerging about the strong predictive relationship between
      self-rated health (SRH) and survival, although there is little evidence on
      palliative populations where an accurate prediction of survival is valuable.
      Thus, the relative importance of SRH in predicting the survival of ambulatory
      patients with advanced cancer was examined. SRH was compared to clinical
      assessments of performance status, as well as to quality-of-life measures.
      PATIENTS AND METHODS: By use of a prospective cohort design, 181 patients (76%
      response rate) with advanced cancer were recruited into the study, resurveyed at
      18 weeks, and observed to record deaths. RESULTS: The average age of patients was
      62 years (SD = 12). The median survival time was 10 months. SRH was the strongest
      predictor of survival from baseline. Also, a Cox regression comparing changes in
      SRH over time yielded hazard ratios suggesting the relative risk (RR) of dying
      was greater for fair ratings at 18 weeks (approximately 3 times) compared with
      consistent good or better ratings; the RR was even greater (4.2 and 6.2 times)
      for poor ratings, especially when ratings were poor at baseline and 18 weeks (31
      times). Improvement in SRH over time yielded the lowest RR. CONCLUSION: SRH is
      valid, reliable, and responsive to change as a predictor of survival of advanced
      cancer. These qualities suggest that SRH should be considered as an additional
      tool by oncologists to assess patients. Similarly, health managers could use SRH
      as an indicator of disease severity in palliative care case mix. Finally, SRH
      could provide a key to help us understand the human side of disease and its
      relationship with medicine.

PMID- 12011131
TI  - Effect of prevention strategies on survival and quality-adjusted survival of
      women with BRCA1/2 mutations: an updated decision analysis.
AB  - PURPOSE: This study updates findings regarding the effects of prophylactic
      surgery, chemoprevention, and surveillance on the survival and quality-adjusted
      survival of women who test positive for BRCA1/2 mutations. MATERIALS AND METHODS:
      Markov modeling of outcomes was performed in a simulated cohort of 30-year-old
      women who tested positive for BRCA1/2 mutations. The model incorporated breast
      and ovarian cancer incidence rates from the literature and mortality rates from
      the Surveillance, Epidemiology, and End Results Program. Quality adjustment of
      survival estimates were obtained from a survey of women aged 33 to 50 years.
      Sensitivity analyses were performed of varied assumptions regarding timing and
      effects of preventive measures on cancer incidence and adverse effects. RESULTS:
      A 30-year-old woman could prolong her survival beyond that associated with
      surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6
      years with prophylactic oophorectomy, 4.6 years with both tamoxifen and
      prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years
      with both surgeries. She could prolong her quality-adjusted survival by 2.8 years
      with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with
      tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both
      surgeries. The benefits of all of these strategies would decrease if they were
      initiated at later ages. CONCLUSION: Women who test positive for BRCA1/2
      mutations may derive greater survival and quality adjusted survival benefits than
      previously reported from chemoprevention, prophylactic surgery, or a combination.
      Observational studies and clinical trials are needed to verify the results of
      this analysis of the long-term benefits of preventive strategies among BRCA1/2
      positive women.

PMID- 12011132
TI  - CEACAM1 expression in cutaneous malignant melanoma predicts the development of
      metastatic disease.
AB  - PURPOSE: The cell adhesion molecule CEACAM1 is involved in intercellular adhesion
      and subsequent signal transduction events in a number of epithelia. CEACAM1
      downregulation has been demonstrated in colorectal and prostate carcinomas. This
      study sought to analyze whether its expression in malignant melanoma is
      associated with metastasis. PATIENTS AND METHODS: CEACAM1 expression was
      immunohistochemically evaluated in 100 primary cutaneous malignant melanomas and
      correlated with metastasis in a 10-year follow-up. Furthermore, CEACAM1
      expression was analyzed in metastatic lesions (11 distant metastases and six
      sentinel lymph node metastases). Univariate Kaplan-Meier analysis and
      multivariate Cox proportional hazard regression analysis adjusted for standard
      prognostic indicators were performed to assess the prognostic relevance of
      CEACAM1 expression. RESULTS: A total of 28 of 40 patients with CEACAM1-positive
      primary melanomas developed metastatic disease, compared with only six of 60
      patients with CEACAM1-negative melanomas. Often, the strongest CEACAM1 expression
      was observed at the invading front. In addition, CEACAM1 expression was preserved
      in the metastatic lesions. Kaplan-Meier analysis revealed a highly significant
      association between CEACAM1 expression and metastasis (P <.0001); multivariate
      Cox regression analysis, including CEACAM1 expression status adjusted for tumor
      thickness, presence of ulceration, and mitotic rate, confirmed that CEACAM1 is an
      independent factor for the risk of metastasis and demonstrated that the
      predictive value of CEACAM1 expression is superior to that of tumor thickness.
      CONCLUSION: Expression of the cell adhesion molecule CEACAM1 in the primary
      tumors in melanoma patients is associated with the subsequent development of
      metastatic disease. This raises the possibility of a functional role for this
      cell adhesion molecule in the metastatic spread it indicates.

PMID- 12011133
TI  - Preoperative paclitaxel and concurrent rapid-fractionation radiation for
      resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and
      event-free outcome.
AB  - PURPOSE: To evaluate the toxicity of a preoperative regimen of paclitaxel and
      concurrent external-beam radiation therapy, pancreaticoduodenectomy, and electron
      beam intraoperative radiation therapy (EB-IORT) for patients with resectable
      pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with localized,
      potentially resectable pancreatic adenocarcinoma were treated with 30 Gy external
      beam radiation therapy and concomitant weekly 3-hour infusions of paclitaxel (60
      mg/m(2)). Radiographic restaging was performed 4 to 6 weeks after chemoradiation,
      and patients with localized disease underwent pancreatectomy with EB-IORT.
      RESULTS: Thirty-five patients completed chemoradiation; 16 (46%) experienced
      grade 3 toxicity. Four patients (11%) required hospitalization for dehydration
      due to grade 3 nausea and vomiting. Twenty (80%) of 25 patients who underwent
      surgery underwent pancreatectomy; EB-IORT was used in 13 patients. There were no
      histologic complete responses to preoperative therapy; 21% of specimens
      demonstrated more than 50% nonviable cells (grade 2b treatment effect). With a
      median follow-up period of 46 months, the 3-year overall survival rate with
      chemoradiation and pancreatectomy was 28%. CONCLUSION: Preoperative paclitaxel
      based concurrent chemoradiation is feasible. The toxicity of this regimen seems
      greater than that with fluorouracil. The histologic responses and survival are
      similar, suggesting no advantages to paclitaxel-based preoperative treatment.

PMID- 12011134
TI  - Bolus fluorouracil and leucovorin with oxaliplatin as first-line treatment in
      metastatic colorectal cancer.
AB  - PURPOSE: A phase II trial investigated the activity and toxicity of a bolus
      administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV)
      therapy in patients with untreated advanced colorectal cancer. PATIENTS AND
      METHODS: Forty-five patients in this multicenter, open, nonrandomized study
      received oxaliplatin 130 mg/m(2) on the first day of each course and 5-FU and LV
      350 mg/m(2) and 20 mg/m(2), respectively, as a daily bolus for 5 days, every 21
      days, for a maximum of six courses. RESULTS: Partial responses occurred in 18
      patients, giving an intent-to-treat response rate of 40.0%. Median time to
      response was 12.7 weeks; median duration of response was 18.4 weeks. Median
      progression-free survival was 5.9 months; median survival was 14 months. The
      independent prognostic factors for improved overall survival were good
      performance status and negative carcino-embryonic antigen blood level. Incidences
      of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m(2).
      Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION: Bolus
      administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated
      advanced colorectal cancer is efficacious and safe. In addition to a more
      favorable safety profile, the 300 mg/m(2) dosage offered improved dose-intensity
      compared with the initial dosage.

PMID- 12011135
TI  - Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline
      pretreated breast cancer patients.
AB  - PURPOSE: Phase II study evaluating efficacy and safety of combined
      oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic
      breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and
      anthracycline-pretreated (within 6 months of study entry) women were treated with
      oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000
      mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median
      patient age was 51 years (range, 34 to 71 years), with a median of two involved
      organs (range, one to six organs), and metastases in the liver (70%), bone (47%),
      and lung (34%). Patients had a median of two prior chemotherapy regimens (range,
      one to six regimens), and 78% had previous hormonal therapy, with clinical taxane
      and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles
      were administered, with a median of six cycles/patient (range, one to 15 cycles).
      Sixty patients were assessable for response (World Health Organization criteria):
      17 partial response, 26 stable disease, and 17 disease progression, giving an
      overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26%
      and 36% in taxane- and anthracycline-resistant populations, respectively, all
      responders having metastatic liver disease. Median time to progression was 4.8
      months, and median overall survival was 11.9 months. Four treatment-related
      serious adverse events occurred, seven patients withdrew because of treatment
      related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4
      neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients,
      respectively, and a single episode of febrile neutropenia. One third of patients
      developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with
      grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective
      with an excellent safety profile in anthracycline/taxane-pretreated ABC patients,
      showing encouraging activity in patients with anthracycline/taxane-resistance or
      visceral disease.

PMID- 12011136
TI  - Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and
      Chinese women with operable breast cancer.
AB  - PURPOSE: In 1992, the Early Breast Cancer Trialists' Collaborative Group reported
      that a meta-analysis of six randomized trials in European and North American
      women begun from 1948 to 1972 demonstrated disease-free and overall survival
      benefit from adjuvant ovarian ablation. Approximately 350,000 new cases of breast
      cancer are diagnosed annually in premenopausal Asian women who have lower levels
      of estrogen than western women. PATIENTS AND METHODS: From 1993 to 1999, we
      recruited 709 premenopausal women with operable breast cancer (652 from Vietnam,
      47 from China) to a randomized clinical trial of adjuvant oophorectomy and
      tamoxifen (20 mg orally every day) for 5 years or observation and this combined
      hormonal treatment on recurrence. At later dates estrogen- and progesterone
      receptor protein assays by immunohistochemistry were performed for 470 of the
      cases (66%). RESULTS: Treatment arms were well balanced. With a median follow-up
      of 3.6 years, there have been 84 events and 69 deaths in the adjuvant treatment
      group and 127 events and 91 deaths in the observation group, with 5-year disease
      free survival rates of 75% and 58% (P =.0003 unadjusted; P =.0075 adjusted), and
      overall survival rates of 78% and 70% (P =.041 unadjusted) for the adjuvant and
      observation groups, respectively. Only patients with hormone receptor-positive
      tumors benefited from the adjuvant treatment. In Vietnam, for women unselected
      for hormone receptor status, a cost-effectiveness analysis suggests that this
      intervention costs $350 per year of life saved. CONCLUSION: Vietnamese and
      Chinese women with hormone receptor-positive operable breast cancer benefit from
      adjuvant treatment with surgical oophorectomy and tamoxifen.

PMID- 12011137
TI  - Phase I and pharmacokinetic study of novel L-nucleoside analog troxacitabine
      given as a 30-minute infusion every 21 days.
AB  - PURPOSE: Troxacitabine (Troxatyl, BCH-4556; BioChem Pharma Inc, Basingstoke,
      United Kingdom) is a novel synthetic L-nucleoside analog with activity against a
      broad range of human tumors in preclinical models. Preclinical toxicity suggested
      a predictable toxicity profile consistent with an agent of this class, with
      evidence of interspecies differences. We conducted a phase I study of
      troxacitabine given as a 30-minute infusion once every 21 days. PATIENTS AND
      METHODS: The starting dose of troxacitabine was 0.025 mg/m(2), based on
      toxicology data from the most sensitive species studied (cynomolgus monkey).
      Doses were doubled until grade 1 skin or mucosal or grade 2 other toxicity was
      encountered. A modified Fibonacci scale was used. RESULTS: A total of 45 patients
      were enrolled at 13 dose levels. Most common nonhematologic side effects were
      skin rash (44%), lethargy (29%), nausea (24%), alopecia, dry skin (18%), anorexia
      (13%), neurosensory symptoms (13%), and hand-foot syndrome (13%). In patients
      treated with prednisone 25 mg/d orally for 5 days, starting on day 1, skin rash
      was less problematic. Two patients at 12.5 mg/m(2) experienced dose-limiting
      (grade 4) granulocytopenia. Confirmed partial responses were documented in one
      patient with previously untreated renal cell carcinoma with metastatic lung and
      bone lesions and in one patient with an unknown primary tumor. Eighteen patients
      had a best response of stable disease with a median duration of 5.1 months
      (range, 2.1 to 18.7 months). CONCLUSION: When given in this schedule, the maximum
      tolerated dose of troxacitabine is 12.5 mg/m(2), and the recommended dose for
      additional phase II studies is 10 mg/m(2) once every 21 days with steroid
      premedication.

PMID- 12011138
TI  - Melatonin: from basic research to cancer treatment clinics.
AB  - Melatonin, the chief secretory product of the pineal gland, is a direct free
      radical scavenger, an indirect antioxidant, as well as an important
      immunomodulatory agent. In both in vitro and in vivo investigations, melatonin
      protected healthy cells from radiation-induced and chemotherapeutic drug-induced
      toxicity. Furthermore, several clinical studies have demonstrated the potential
      of melatonin, either alone or in combination with traditional therapy, to yield a
      favorable efficacy to toxicity ratio in the treatment of human cancers. This
      study reviews the literature from laboratory investigations that document the
      antioxidant and oncostatic actions of melatonin and summarizes the evidence
      regarding the potential use of melatonin in cancer treatment. This study also
      provides rationale for the design of larger translational research-based clinical
      trials.

PMID- 12011139
TI  - Laparoscopic sentinel node procedure in patients with cervical cancer.

PMID- 12011140
TI  - Preoperative chemotherapy in non-small-cell lung cancer: nothing new in N2
      disease.

PMID- 12011141
TI  - Adequate lymph node staging is fundamental to comparative study on resectable non
      small-cell lung cancer.

PMID- 12011142
TI  - Follow-up after Port-a-cath-induced thrombosis.

PMID- 12011143
TI  - Robinow syndrome.
AB  - In 1969, Robinow and colleagues described a syndrome of mesomelic shortening,
      hemivertebrae, genital hypoplasia, and "fetal facies". Over 100 cases have now
      been reported and we have reviewed the current knowledge of the clinical and
      genetic features of the syndrome. The gene for the autosomal recessive form was
      identified as the ROR2 gene on chromosome 9q22. ROR2 is a receptor tyrosine
      kinase with orthologues in mouse and other species. The same gene, ROR2, has been
      shown to cause autosomal dominant brachydactyly B, but it is not known at present
      whether the autosomal dominant form of Robinow syndrome is also caused by
      mutations in ROR2.

PMID- 12011145
TI  - Malignant peripheral nerve sheath tumours in neurofibromatosis 1.
AB  - BACKGROUND: Cross sectional studies have shown that 1-2% of patients with
      neurofibromatosis 1 (NF1) develop malignant peripheral nerve sheath tumours
      (MPNST). However, no population based longitudinal studies have assessed lifetime
      risk. METHODS: NF1 patients with MPNST were ascertained from two sources for our
      north west England population of 4.1 million in the 13 year period 1984-1996: the
      North West Regional NF1 Register and review of notes of patients with MPNST in
      the North West Regional Cancer Registry. RESULTS: Twenty-one NF1 patients
      developed MPNST, equivalent to an annual incidence of 1.6 per 1000 and a lifetime
      risk of 8-13%. There were 37 patients with sporadic MPNST. The median age at
      diagnosis of MPNST in NF1 patients was 26 years, compared to 62 years in patients
      with sporadic MPNST (p<0.001). In Kaplan-Meier analyses, the five year survival
      from diagnosis was 21% for NF1 patients with MPNST, compared to 42% for sporadic
      cases of MPNST (p=0.09). One NF1 patient developed two separate MPNST in the
      radiation field of a previous optic glioma. CONCLUSION: The lifetime risk of
      MPNST in NF1 is much higher than previously estimated and warrants careful
      surveillance and a low threshold for investigation.

PMID- 12011146
TI  - Molecular genetic analysis of the NF2 gene in young patients with unilateral
      vestibular schwannomas.
AB  - Neurofibromatosis type 2 (NF2) must be suspected in patients presenting with a
      unilateral vestibular schwannoma at a young age who are therefore at theoretical
      risk of developing bilateral disease. We identified 45 patients aged 30 years or
      less at the onset of symptoms of a unilateral vestibular schwannoma. Molecular
      genetic analysis of the NF2 gene was completed on peripheral blood samples in all
      45 and on 28 tumour samples. No pathogenic NF2 mutations were identified in any
      of the blood samples. NF2 point mutations were identified in 21/28 (75%) tumour
      samples and loss of heterozygosity (LOH) in 21/28 (75%) tumour samples. Both
      mutational hits were identified in 18/28 (65%) tumour samples. In one
      multilobular tumour, one (presumably first hit) mutation was confirmed which was
      common to different foci of the tumour, while the second mutational event
      differed between foci. The molecular findings in this patient were consistent
      with somatic mosaicism for NF2 and the clinical diagnosis was confirmed with the
      presence of two meningiomas on a follow up MRI scan. A further patient developed
      a contralateral vestibular schwannoma on a follow up MRI scan in whom neither of
      the truncating mutations in the vestibular schwannoma were present in blood. It
      is important when counselling patients with unilateral vestibular schwannomas to
      identify (1) those at risk of bilateral disease, (2) those at risk of developing
      other tumours, and (3) other family members at risk of developing NF2. Comparing
      tumour and blood DNA cannot exclude mosaicism in the index case and cannot,
      therefore, be used to predict those at risk of developing further tumours.
      However, identification of both mutations or one mutation plus LOH in the tumour
      and exclusion of those mutations in the blood samples of the sibs or offspring of
      the affected case may be sufficient to render further screening unnecessary in
      these relatives.

PMID- 12011148
TI  - An MLH1 haplotype is over-represented on chromosomes carrying an HNPCC
      predisposing mutation in MLH1.
AB  - BACKGROUND: The mismatch repair gene, MLH1, appears to occur as two main
      haplotypes at least in white populations. These are referred to as A and G types
      with reference to the A/G polymorphism at IVS14-19. On the basis of preliminary
      experimental data, we hypothesised that deviations from the expected frequency of
      these two haplotypes could exist in carriers of disease associated MLH1 germline
      mutations. METHODS: We assembled a series (n=119) of germline MLH1 mutation
      carriers in whom phase between the haplotype and the mutation had been
      conclusively established. Controls, without cancer, were obtained from each
      contributing centre. Cases and controls were genotyped for the polymorphism in
      IVS14. RESULTS: Overall, 66 of 119 MLH1 mutations occurred on a G haplotype
      (55.5%), compared with 315 G haplotypes on 804 control chromosomes (39.2%,
      p=0.001). The odds ratio (OR) of a mutation occurring on a G rather than an A
      haplotype was 1.93 (95% CI 1.29 to 2.91). When we compared the haplotype
      frequencies in mutation bearing chromosomes carried by people of different
      nationalities with those seen in pooled controls, all groups showed a ratio of
      A/G haplotypes that was skewed towards G, except the Dutch group. On further
      analysis of the type of each mutation, it was notable that, compared with control
      frequencies, deletion and substitution mutations were preferentially represented
      on the G haplotype (p=0.003 and 0.005, respectively). CONCLUSION: We have found
      that disease associated mutations in MLH1 appear to occur more often on one of
      only two known ancient haplotypes. The underlying reason for this observation is
      obscure, but it is tempting to suggest a possible role of either distant
      regulatory sequences or of chromatin structure influencing access to DNA
      sequence. Alternatively, differential behaviour of otherwise similar haplotypes
      should be considered as prime areas for further study.

PMID- 12011149
TI  - Genome screening of coeliac disease.

PMID- 12011151
TI  - Association of Crohn's disease and ulcerative colitis with haplotypes of the MLH1
      gene in Italian inflammatory bowel disease patients.

PMID- 12011152
TI  - Hereditary non-polyposis colorectal cancer: current risks of colorectal cancer
      largely overestimated.

PMID- 12011155
TI  - Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather
      than the cationic trypsinogen gene (PRSS1) are significantly associated with
      tropical calcific pancreatitis.

PMID- 12011154
TI  - Naturally occurring mutations and functional polymorphisms in multidrug
      resistance 1 gene: correlation with microsatellite instability and lymphoid
      infiltration in colorectal cancers.

PMID- 12011157
TI  - Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital
      cataracts.

PMID- 12011158
TI  - Alport syndrome and mental retardation: clinical and genetic dissection of the
      contiguous gene deletion syndrome in Xq22.3 (ATS-MR).

PMID- 12011159
TI  - Changes in frequencies of heterozygous thermolabile 5,10
      methylenetetrahydrofolate reductase gene in fetuses with neural tube defects.

PMID- 12011160
TI  - Maternal MTHFR genotype contributes to the risk of non-syndromic cleft lip and
      palate.

PMID- 12011161
TI  - Major difference in aetiology and phenotypic abnormalities between transient and
      permanent neonatal diabetes.

PMID- 12011162
TI  - A T to C mutation in the polypyrimidine tract of the exon 9 splicing site of the
      RB1 gene responsible for low penetrance hereditary retinoblastoma.

PMID- 12011163
TI  - Spinocerebellar ataxia and the A3243G and A8344G mtDNA mutations.

PMID- 12011164
TI  - Partial deletion of 4p and 4q in a fetus with ring chromosome 4: phenotype and
      molecular mapping of the breakpoints.

PMID- 12011165
TI  - Comparative genomic hybridisation shows a partial de novo deletion 16p11.2 in a
      neonate with multiple congenital malformations.

PMID- 12011166
TI  - Corpus callosum hypoplasia and associated brain anomalies in Nijmegen breakage
      syndrome.

PMID- 12011167
TI  - Preconceptional couple screening for cystic fibrosis carrier status: couples
      prefer full disclosure of test results.

PMID- 12011168
TI  - Genome scan reveals new coat color loci in exotic pig cross.
AB  - The porcine genome was scanned to identify loci affecting coat color in an
      experimental cross between the Meishan breed and Dutch commercial lines. Linkage
      was studied in 1181 F(2) animals for 132 microsatellite markers and seven binary
      coat color scores: White, Black spotting, Speckle, Gray, Black, and specific
      color phenotypes for head and legs. The analyses were performed using interval
      mapping under various models. The study confirmed the existence of coat color
      loci on chromosome 8 and chromosome 6. One additional locus affecting White was
      detected on chromosome 5, possibly representing the porcine equivalent of the
      steel factor. Two new loci affecting Black were detected on chromosome 2. One of
      these showed exclusive maternal expression and mapped to a region where imprinted
      genes have been reported. The effect of the binary coding was tested by
      additional analyses excluding the white animals (>50% of F(2) animals). This
      showed that Black spotting was strongly influenced by the locus on chromosome 6
      and the other color phenotypes were mainly influenced by the locus on chromosome
      8. Epistatic effects were found between the loci on chromosomes 6 and 8 for Black
      spotting. For Black color, all combinations among chromosomes 2, 6, and 8 showed
      epistatic effects.

PMID- 12011169
TI  - Mitochondrial sequence diversity within a subspecies of savanna monkeys
      (Cercopithecus aethiops) is similar to that between subspecies.
AB  - Cercopithecus aethiops can be classified into four subspecies by morphology and
      by geographic distribution. However, the phylogenetic relationship between these
      subspecies is unclear. We previously found five distinct haplogroups of
      mitochondrial DNA (mtDNA) in the subspecies C. aethiops aethiops at the
      restriction fragment length polymorphism (RFLP) level, and found that those
      haplogroups are parapatrically distributed in their habitat. To determine the
      relationship between subspeciation and haplogroup formation in a subspecies, we
      compared mtDNA control region and 12S rRNA gene sequences (approximately 700 bp)
      in C. a. aethiops, two other subspecies of C. aethiops, and two species of
      Cercopithecus: The diversity between haplogroups in C. a. aethiops was almost the
      same as that between subspecies. This similar level of diversification between
      and within haplogroups may explain why a previously obtained mtDNA tree did not
      show monophyletic branching according to subspecies.

PMID- 12011170
TI  - Mapping a cave fish genome: polygenic systems and regressive evolution.
AB  - We used random amplified polymorphic DNA (RAPD) fingerprinting to generate
      anonymous DNA markers in the fish Astyanax mexicanus, a species with both surface
      and cave populations. Surface individuals are eyed and pigmented; troglobitic
      forms are blind and depigmented. We hybridized surface fish and Pachon population
      cave fish and produced a RAPD genomic map 1064 cM in length (about half the total
      length of the genome) that was used to screen for quantitative trait loci (QTL)
      for troglomorphic traits. Three QTL for reduced eye size, two for decreased
      numbers of melanophores, two for condition factor, and the locus for the
      unifactorial trait, albinism, were mapped. These factors account for an average
      of 46% of the variance in these traits in the backcross. The results are the
      first direct demonstration that troglomorphic changes in this population are
      multifactorial. Two closely linked pairs of QTL were found. Each consisted of a
      regressive and a constructive trait QTL. These close linkages are unlikely to
      have occurred by chance (P <.05 for each) and suggest that troglomorphic
      evolution might be facilitated by pleiotropy or by genetic hitchhiking.

PMID- 12011171
TI  - Selection on a modifier of recombination rate due to linked deleterious
      mutations.
AB  - Several models have been suggested to explain the origin and maintenance of
      recombination. Here I present the results from computer simulations of multilocus
      haploid and diploid genotypes in small populations. Each chromosome consisted of
      1001 loci where deleterious mutations occurred. At "equilibrium" for mutation
      selection-genetic drift balance a single recombination variant was introduced to
      the population in the middle of a chromosome. On average 75,000 replicates for
      each combination of parameters were followed to fixation or loss of the modifier
      allele. The results show that, in a small population, increased recombination can
      be selected, even in the absence of epistasis or beneficial mutations. The effect
      of the mutation rate for deleterious mutations depends on the ploidy level and
      the recessiveness of deleterious mutations. A higher deleterious mutation rate is
      required for an increase in recombination rate to be favored in haploid
      populations. Increased recombination could not evolve in the case of strong
      associative overdominance.

PMID- 12011172
TI  - Characterization of genetic markers for in vitro cell line identification of the
      marine sponge Axinella corrugata.
AB  - The marine sponge Axinella corrugata is being developed as a model organism for
      in vitro marine invertebrate research. Molecular genetics methods such as DNA
      fingerprinting [amplified fragment length polymorphism (AFLP) and single-stranded
      conformation polymorphism (SSCP)] and single-locus DNA sequence analyses were
      applied to this model to meet the primary objective of identifying positive A.
      corrugata-specific molecular markers that will aid in verifying cell identity in
      vitro and distinguish sponge cells from potential microbial contaminants. The
      extent of intra- and interspecific variation in these markers from geographically
      distinct samples of A. corrugata and closely related sponge taxa was also
      assessed. Two novel nuclear loci along with intervening transcribed spacer (ITS)
      regions of nuclear rRNA were characterized, although the latter appeared to
      better meet primary marker criteria, such as taxonomic specificity and high
      frequency of detection (via polymerase chain reaction [PCR]) from different
      individuals (n > 40) and cell cultures. Phylogenetic and phylogeographic analyses
      of ITS DNA sequences helped clarify taxonomies and also suggested species
      boundaries between and among western Atlantic and eastern Atlantic/Indian Ocean
      A. corrugata and Axinellidae samples. Patterns of genetic variation have
      important implications for the systematics, evolution, and chemical ecology of A.
      corrugata and related axinellids and are discussed.

PMID- 12011173
TI  - Genetic variation and evidence of hybridization in the genus Rhus
      (Anacardiaceae).
AB  - Rhus michauxii, a rare plant species endemic to the southeastern United States,
      was previously known only from central North Carolina and one site in Georgia. An
      additional site, which is now believed to represent the largest known
      concentration of R. michauxii, was recently discovered at Ft. Pickett near
      Blackstone, Virginia. Morphological characteristics in several of the Ft. Pickett
      Rhus populations appear to be intermediate between R. michauxii and the
      widespread R. glabra, a closely related congener that co-occurs at Ft. Pickett.
      Although morphological evidence of hybridization between R. michauxii and R.
      glabra in North Carolina has been provided previously, genetic marker data are
      lacking. In the present study we examined levels of allozyme variation at 11
      polymorphic loci within and among seven populations of R. michauxii, one
      population of R. glabra, and four putative hybrid populations at Ft. Pickett.
      Overall, R. michauxii had typical levels of within-population genetic variation
      when compared to other species with similar life-history characteristics. In
      contrast, the proportion of genetic variation among populations (G(ST)) was
      considerably lower than expected. Finally, R. michauxii and R. glabra appear to
      have a fixed allelic difference at the Idh2 locus. This enabled us to confirm
      hybridization in all four of the putative hybrid populations and one of the R.
      michauxii populations.

PMID- 12011174
TI  - Maize tertiary trisomic stocks derived from B-A translocations.
AB  - Reciprocal translocations between supernumerary B chromosomes and the basic
      complement of A chromosomes in maize have resulted in a powerful set of tools to
      manipulate the dosage of chromosomal segments. From 15 B-A reciprocal
      translocation stocks that have the B-A chromosome genetically marked we have
      developed tertiary trisomic stocks. Tertiary trisomics are 2n + 1 aneuploids
      where the extra chromosome is a translocation element, in this case a B-A
      chromosome. Whereas B-A translocations produce aneuploidy in the sperm, the
      tertiary trisomic plant efficiently transmits hyperploid gametes maternally.
      Because the B-A tertiary trisomic stocks and the B-A translocation stocks from
      which they were derived are introgressed into the W22 inbred line, the effects of
      maternally and paternally transmitted trisomic B-A chromosomes can be compared.
      Data are presented on both the male and female transmission rates of the B-A
      chromosomes in the tertiary trisomic stocks.

PMID- 12011175
TI  - Two recessive gene inheritance for triallate resistance in Avena fatua L.
AB  - Extensive use of the preemergence herbicide triallate over the last three decades
      has selected for resistant (R) Avena fatua L. populations in several areas of the
      United States and Canada. R plants are also cross-resistant to the unrelated
      pyrazolium herbicide difenzoquat. We made reciprocal crosses between inbred R and
      susceptible (S) lines to determine the genetic basis of triallate resistance.
      Seeds from parental lines and F(2) populations were treated with soil
      applications of 0.275, 0.55, or 1.1 kg/ha triallate in the greenhouse and plant
      heights recorded after 37 days. Surviving F(2) plants were selfed and the
      resulting F(3) families were screened with 1.1 kg/ha triallate. In the F(2)
      populations, assortment of S and R phenotypes fit a 15:1 segregation ratio,
      suggesting that resistance was controlled by the two independently segregating
      recessive genes TRR1 and TRR2. None of the 912 F(3) progeny from 51 R F(2)
      individuals was susceptible to triallate treatment, further supporting a two-gene
      mode of inheritance. There was a possible maternal effect on susceptibility at
      the highest triallate rate tested.

PMID- 12011176
TI  - Inheritance of disease lesion mimic leaf trait in groundnut.
AB  - In groundnut, two identical mutants with disease lesion mimic leaf trait were
      isolated independently from two different parents through induced mutagenesis and
      in vitro culture technique. The leaf chlorophyll content in both the mutants was
      found to be drastically reduced. The segregation pattern in the F(2) and F(3)
      generations for normal and mutant traits fitted a 13:3 ratio, indicating that the
      disease lesion mimic trait in the mutants was due to suppressive gene action.
      Both mutants were allelic for the disease mimic trait.

PMID- 12011177
TI  - Genetics of qualitative traits in domesticated chia (Salvia hispanica L.).
AB  - In Salvia hispanica L., several changes in qualitative characters, including seed
      coat color, stem pigmentation, and shattering, have evolved with cultivation and
      domestication. Three F(2) segregating generations from crosses between wild and
      domesticated parents were scored for three qualitative traits. A single recessive
      gene, designated scc, was found to govern the white seed characteristic. A single
      dominant gene, designated SSP, was found to control striated stem pigmentation. A
      complete dominance of open calyx over closed calyx was observed in F(1)
      generations and small numbers of plants with closed calyxes were observed in F(2)
      generations, not conforming to Mendelian ratios. For this non-shattering trait, a
      complementation test was conducted between two lines representative of
      geographically and morphologically divergent domesticated varieties.
      Complementary gene action was not observed in any F(1) plants, and all F(2)
      plants were homogeneous with respect to the trait, suggesting the same genetic
      control for non-shattering among domesticated varieties. An analysis of limited
      data for linkage of SSP and scc indicated that the two loci segregate
      independently.

PMID- 12011178
TI  - Inheritance of flower color in periwinkle: orange-red corolla and white eye.
AB  - The commonly found flower colors in periwinkle (Catharanthus roseus)--pink,
      white, red-eyed, and pale pink center--are reported to be governed by the
      epistatic interaction between four genes--A, R, W, and I. The mode of inheritance
      of an uncommon flower color, orange-red corolla and white eye, was studied by
      crossing an accession possessing this corolla color with a white flowered variety
      (Nirmal). The phenotype of the F(1) plants and segregation data of F(2) and
      backcross generations suggested the involvement of two more interacting and
      independently inherited genes, one (proposed symbol E) determining the presence
      or absence of red eye and another (proposed symbol O) determining orange-red
      corolla.

PMID- 12011179
TI  - Thirty polymorphic nuclear microsatellite loci from black walnut.
AB  - Black walnut (Juglans nigra L) is a large tree, native to the eastern United
      States, that is prized for its high-quality timber and edible nut. Thirty
      (GA/CT)n nuclear microsatellite markers were identified from black walnut for use
      in population genetic studies, genome mapping, DNA genotyping of important
      clones, studies of gene flow, and tree breeding. The markers were polymorphic
      based on a diversity panel of 10 black walnut individuals from eight Midwestern
      U.S. states.

PMID- 12011180
TI  - Inheritance and linkage of allozymes in a Balkan endemic, Pinus peuce Griseb.
AB  - This article presents a study of isozyme variation in Pinus peuce Griseb., a
      Balkan endemic. Among the enzyme systems studied, five were monomorphic and eight
      were polymorphic in at least one locus. The segregation analysis of the
      polymorphic loci were consistent with a Mendelian mode of inheritance. No
      significant deviation from the expected ratio was observed both at the individual
      and pooled segregation data levels. Segregation patterns were homogeneous across
      individuals. Two significant linkage groups were found in P. peuce: FEST-2:LAP-2
      and 6PG-1:6PG-2, which correspond to the results obtained for other pine species.

PMID- 12011181
TI  - Heterologous amplification of microsatellite markers from colubroid snakes in
      European natricines (serpentes: natricinae).
AB  - Eighteen microsatellite loci developed for a range of snake species (New World
      natricines, elapids, crotalids) were tested against European natricines (Natrix
      natrix, N. maura, and N. tessellata) in cross-species amplification experiments.
      Five loci were polymorphic (average expected heterozygosity 0.749 for a
      population of N. natrix in Amsterdam, mean sample size 47.8) and three loci were
      monomorphic. The remainder could not be consistently scored or failed to amplify.
      Further tests on single individuals of a diverse set of eight species of
      colubroid snakes showed that 15 of the 18 loci could be cross-amplified in at
      least one of these species. We conclude that our results show promise for the
      utilization of these markers for experimental assessments of genetic variation in
      the phylogenetically closely related group of European natricine snakes with
      emphasis on N. natrix. The full suite of microsatellite markers now available for
      snakes may show additional potential for subsequent investigation across a
      broader range of colubroid snakes.

PMID- 12011182
TI  - Inheritance of null alleles for microsatellites in the white pine weevil
      (Pissodes strobi [Peck] [Coleoptera: Curculionidae]).
AB  - Four families of the white pine weevil (Pissodes strobi) produced by controlled
      breeding were used to study the mode of inheritance at four microsatellite loci.
      The results confirmed the Mendelian segregation of all loci. Three of the four
      loci showed the presence of null alleles. The observed high polymorphism of P.
      strobi microsatellites increased their usefulness for paternity determination.
      The presence of null alleles predicates the need to redesign primers before using
      them in population genetics studies where pedigree is unknown.

PMID- 12011183
TI  - Characterization of three microsatellite loci linked to the canine RP3 interval.
AB  - X-linked retinitis pigmentosa (XLRP) is one of the most prevalent forms of a
      genetically heterogeneous group of inherited retinal disorders of man; more than
      70% of XLRP families map to the RP2 or RP3 loci on the human X chromosome. Canine
      X-linked progressive retinal atrophy (XLPRA), observed in the Siberian husky, is
      the locus homologue of human RP3, but the gene responsible for XLPRA has not yet
      been identified. To develop polymorphic markers in the RP3 interval in dogs we
      have isolated microsatellites from canine BAC clones. Three tightly linked
      microsatellite loci, CUX20001, CUX30001, and CUX40002, have been investigated in
      17 dog breeds or breed varieties. Calculated parameters of variability correspond
      with the number of repeats at each locus. Pedigree analyses showed tight linkage
      between the canine t-complex-associated testis-expressed 1-like gene (TCTE1l) and
      the gene ornithine carbamoyltransferase (OTC). Each microsatellite shows
      conservation within Canidae, and CUX20001 also amplified in Mustelidae and
      URSIDAE: These markers represent an important tool in the fine mapping process
      for the canine region homologous to the RP3 disease interval and are valuable for
      evaluation of conservation and homology of this region among related species.

PMID- 12011184
TI  - Testing homology of loci for two plumage colors, "lavender" and "recessive
      white," with chicken and Japanese quail hybrids.
AB  - Homology for two plumage color loci was studied by hybridization between chickens
      and Japanese quail. First, chicken-quail hybrids were produced from homozygous
      "lavender" chicken cocks and "bleu" Japanese quail, and all 30 hybrids had the
      same parental slate blue plumage color. On the other hand, no hybrids with this
      plumage were obtained out of 18 progeny from the same cocks and wild-type quail.
      These results show that the slate blue plumage color is determined by homologous
      loci in Japanese quail and chickens. Second, all (n = 25) chicken-quail hybrids
      hatched from homozygous "recessive white" cocks and "recessive white" (n = 8) or
      "wild-type" (n = 17) quail had the same pattern of plumage color, with white
      feathers on the ventral face and colored feathers elsewhere. These results
      indicate that the recessive white mutations are not homologous in Japanese quail
      and chickens.

PMID- 12011185
TI  - MapChart: software for the graphical presentation of linkage maps and QTLs.

PMID- 12011189
TI  - Understanding the basic concepts of public health surveillance.

PMID- 12011190
TI  - Fighting against Chagas' disease in the Guarani communities in Bolivia.

PMID- 12011191
TI  - Is the prevalence of coronary heart disease falling in British men?

PMID- 12011192
TI  - The consequences of flexible work for health: are we looking at the right place?

PMID- 12011193
TI  - "Walk in to Work Out": a randomised controlled trial of a self help intervention
      to promote active commuting.
AB  - STUDY OBJECTIVE: To determine if a self help intervention, delivered via written
      interactive materials (the "Walk in to Work Out" pack), could increase active
      commuting behaviour (walking and cycling). DESIGN: Randomised controlled trial.
      The intervention group received the "Walk in to Work Out" pack, which contained
      written interactive materials based on the transtheoretical model of behaviour
      change, local information about distances and routes, and safety information. The
      control group received the pack six months later. Focus groups were also
      conducted after six months. SETTING: Three workplaces in the city of Glasgow,
      Scotland, UK. PARTICIPANTS: 295 employees who had been identified as thinking
      about, or doing some irregular, walking or cycling to work. MAIN RESULTS: The
      intervention group was almost twice as likely to increase walking to work as the
      control group at six months (odds ratio of 1.93, 95% confidence intervals 1.06 to
      3.52). The intervention was not successful at increasing cycling. There were no
      distance travelled to work, gender, or age influences on the results. Twenty five
      per cent (95% confidence intervals 17% to 32%) of the intervention group, who
      received the pack at baseline, were regularly actively commuting at the 12 month
      follow up. CONCLUSION: The "Walk in to Work Out" pack was successful in
      increasing walking but not cycling. The environment for cycling must be improved
      before cycling will become a popular option.

PMID- 12011194
TI  - Bunk versus conventional beds: a comparative assessment of fall injury risk.
AB  - OBJECTIVE: To depict the magnitude and spectrum of childhood injuries
      attributable to falls from bunk beds in comparison with conventional beds and to
      outline sociodemographic risk factors and injury characteristics. STUDY DESIGN:
      Case-control investigation. SETTING: Accident and emergency departments of four
      hospitals in Greece, namely a teaching children's hospital and a trauma hospital
      in Greater Athens and the two district hospitals in the Magnesia county and the
      Corfu island. PATIENTS: During the three year period 1996-98, 1881 children (0-14
      years) presenting with bed fall injuries were recorded by the Emergency
      Department Injury Surveillance System (EDISS). Out of these, 197 children with
      falls from bunk beds served as cases and 1684 children with falls from
      conventional beds served as controls. RESULTS: From the analysis and a nationwide
      extrapolation, it was calculated that each year about 5000 children in Greece
      (total population 10 million) seek medical attendance at an emergency department
      for a bed injury, corresponding to an estimated incidence of about 3 per 1000
      children years. Out of bed fall injuries, 10.5% are from bunk beds, 10.4% from
      cribs, 3.1% from cots, and 76.0% from other conventional beds. Falls from the bed
      ladder accounted for 8% of all bunk bed injuries. Boys are at higher risk for
      falls from beds but there is no evidence that the proportion is different
      depending on the type of bed used. Relatively few falls from bunk beds are
      recorded outside the crowded apartments of Greater Athens or among migrant
      children. The increased relative risk of injuries from bunk bed falls during the
      sleeping hours indicates the higher risk of injury after a fall from a bunk
      rather than a conventional bed. Injuries from bunk bed falls are generally more
      serious than those from conventional bed falls (overrepresentation of brain
      injuries, fractures, multiple injuries, and injuries requiring hospitalisation).
      Overall, it can be estimated that almost half of the sleep related bunk bed
      injuries are easily preventable. CONCLUSIONS: Falls from bunk beds represent a
      non-negligible childhood injury risk. A sizeable fraction can be avoided with
      simple design modifications of the product, such as use of side rails in the
      upper bed or removal of the bed ladder when not in use.

PMID- 12011195
TI  - Influence of patient gender on admission to intensive care.
AB  - STUDY OBJECTIVES: To compare the case mix and outcomes of male and female
      patients admitted to intensive care units for a wide range of conditions. DESIGN:
      Cross sectional study of prospectively collected data. SETTING: The Intensive
      Care National Audit and Research Centre, (ICNARC) Case Mix Programme.
      PARTICIPANTS: 46 587 admissions to 91 units across England, Wales, and Northern
      Ireland. MAIN RESULTS: No gender differences were found in case mix on admission
      or in mortality for five conditions (cardiac arrhythmia, chronic obstructive
      airways disease, asthma, self poisoning, and seizures). There was some evidence
      of horizontal and vertical inequity for female patients with myocardial
      infarction and with neurological bleeding. Vertical equity was not achieved for
      male pneumonia and ventricular failure patients and for women with primary brain
      injury. CONCLUSIONS: This study demonstrated, for the first time, possible
      inequitable use of intensive care for patients with certain conditions. This may
      be secondary to gender bias and can result in either over-treatment in the
      favoured group, or under-treatment in the neglected group. It would therefore be
      pertinent to re-examine these findings using other databases, and to further
      investigate the causative factors, including gender bias.

PMID- 12011196
TI  - Lung cancer: district active treatment rates affect survival.
AB  - STUDY OBJECTIVE: This study investigates variation in management and treatment of
      lung cancer patients and determines the impact of any variation in treatment on
      survival. DESIGN: A retrospective study of population based data held by the
      Northern & Yorkshire Cancer Registry and Information Service (NYCRIS), comparing
      active treatment rates for lung cancer with survival by districts. SETTING The
      then 17 districts in Yorkshire and South Humber, England. PATIENTS: 22 654
      patients registered with lung cancer between 1986 and 1994 and followed up until
      end of 1996. RESULTS: The overall rates of active treatment (surgery,
      radiotherapy, and chemotherapy) varied between districts from 37% to 56%. One
      year survival (with 95% CI) was significantly better in the districts with
      highest rates of active treatment 23% (22% to 24%) compared with 19% (17% to 20%)
      for those with lowest treatment rates. Non-small cell lung cancer patients (55%)
      in the districts with highest active treatment rates had an age adjusted relative
      risk of death during the follow up period, relative to risk of death in the
      districts with the lower treatment rates of 0.88 (0.83 to 0.92). Clinically
      diagnosed patients (34%) had an age adjusted RR of 0.92 (0.86 to 0.96). RR in
      small cell cancer (11%) was not significant. CONCLUSION: This study has shown
      wide variations in the rates of active treatment for lung cancer patients within
      districts across one large region of England. Active treatment was strongly
      associated with improved survival, especially in non-small cell lung cancer.

PMID- 12011197
TI  - Mortality and morbidity surrounding coronary artery bypass surgery and the public
      presentation of risk.

PMID- 12011198
TI  - Exposure to extremely low frequency magnetic fields among primary school children
      in Spain.

PMID- 12011199
TI  - Health inequalities in Britain: continuing increases up to the end of the 20th
      century.

PMID- 12011201
TI  - Determinants of health inequalities by income from the 1980s to the 1990s in
      Finland.

PMID- 12011200
TI  - Income inequality and self rated health in Britain.
AB  - STUDY OBJECTIVE: Several studies have reported an association between income
      inequality and increased mortality, but few have used net income data, controlled
      for individual income, or evaluated sensitivity to the choice of inequality
      measure. The study tested the hypotheses that people in regions of Britain with
      the greatest income inequality would report worse health than those in other
      regions, after adjusting for individual socioeconomic circumstances. DESIGN:
      Cross sectional survey. SETTING: England, Wales, and Scotland. PARTICIPANTS: 8366
      people living in private households. MAIN RESULTS: Regional income inequality,
      measured using the Gini index, was associated with worse self rated health,
      especially among those with the lowest incomes (adjusted OR 1.55, 95% CI 1.24 to
      1.92) (p<0.001). This association was not robust to the choice of income
      inequality measure, being maximal for the Gini coefficient and weakest when using
      indices that are more sensitive to income differences among those at the top or
      bottom of the income distribution. CONCLUSIONS: The study found limited evidence
      of an association between income inequality and worse self rated health in
      Britain, which was greatest among those with the lowest individual income levels.
      As regions with the highest income inequality were also the most urban, these
      findings may be attributable to characteristics of cities rather than income
      inequality. The variation in this association with the choice of income
      inequality measure also highlights the difficulty of studying income
      distributions using summary measures of income inequality.

PMID- 12011202
TI  - Changing life expectancy in Romania after the transition.
AB  - BACKGROUND: While Poland, Hungary, and the Czech Republic have seen impressive
      gains in life expectancy in the 1990s, Romania has not. In contrast with the
      other countries, there has been very little research on the causes of the pattern
      of mortality seen in Romania. OBJECTIVES: To describe the trends in life
      expectancy at birth in Romania after the political transition in 1989 and to
      evaluate the contribution of deaths from different causes and different ages to
      these changes. METHODS: Decomposition of life expectancy by age and cause of
      death using routine data on mortality for the years 1990, 1996, and 1998;
      comparison of death rates by age, sex, and cause of death. RESULTS: Romania has
      experienced an overall decline of 1.71 years of life expectancy at birth from
      1990 to 1996 in men and 0.54 years in women. The major contribution to this
      decline was an increase in mortality from cardiovascular diseases and diseases of
      the digestive system, in particular cirrhosis, among the middle aged and elderly.
      The recovery observed in 1998, of 1.12 years in men and 0.89 years in women, was
      mainly caused by a reduction in deaths from cardiovascular disease in the middle
      aged and elderly. Infant and early childhood mortality fell throughout the period
      but there was an increase of approximately 40% in mortality at age 5-9 that was
      almost entirely attributable to AIDS. CONCLUSION: This is the first Romanian
      study that describes the evolution of life expectancy after transition. Romania
      may at last be beginning to follow the path of improving adult mortality seen in
      the early 1990s in some of its neighbours. It has, however, been unique in
      eastern Europe in experiencing increasing childhood mortality. This is
      attributable to an epidemic of paediatric AIDS, consequent on the tragically
      inappropriate policies adopted in the 1980s.

PMID- 12011203
TI  - Effects of chronic job insecurity and change in job security on self reported
      health, minor psychiatric morbidity, physiological measures, and health related
      behaviours in British civil servants: the Whitehall II study.
AB  - STUDY OBJECTIVE: To determine the effect of chronic job insecurity and changes in
      job security on self reported health, minor psychiatric morbidity, physiological
      measures, and health related behaviours. DESIGN: Self reported health, minor
      psychiatric morbidity, physiological measures, and health related behaviours were
      determined in 931 women and 2429 men who responded to a question on job
      insecurity in 1995/96 and again in 1997/99. Self reported health status, clinical
      screening measures, and health related behaviours for participants whose job
      security had changed or who remained insecure were compared with those whose jobs
      had remained secure. SETTING: Prospective cohort study, Whitehall II, all
      participants were white collar office workers in the British Civil Service on
      entry to the study. MAIN RESULTS: Self reported morbidity was higher among
      participants who lost job security. Among those who gained job security residual
      negative effects, particularly in the psychological sphere were observed. Those
      exposed to chronic job insecurity had the highest self reported morbidity.
      Changes in the physiological measures were limited to an increase in blood
      pressure among women who lost job security and a decrease in body mass index
      among women reporting chronic job insecurity. There were no significant
      differences between any of the groups for alcohol over the recommended limits or
      smoking. CONCLUSION: Loss of job security has adverse effects on self reported
      health and minor psychiatric morbidity, which are not completely reversed by
      removal of the threat and which tend to increase with chronic exposure to the
      stressor.

PMID- 12011204
TI  - Acculturation status and hypertension among Asian immigrants in Canada.

PMID- 12011205
TI  - The size of obesity differences associated with educational level in Spain, 1987
      and 1995/97.
AB  - OBJECTIVE: To determine the size of obesity differences associated with
      educational level in the adult population in Spain. DESIGN: Three cross sectional
      studies representative of the adult population in Spain were carried out in 1987,
      1995, and 1997. SETTING: The general population in Spain. PARTICIPANTS: 11 461
      men and 10 219 women aged 25 to 64 years. MAIN RESULTS: For both men and women
      the obesity prevalence was highest in those with elementary education. In 1987
      the obesity prevalence proportion associated with less than third level education
      (PA) was 24.5% (95% CI 6.0 to 42.8) and 47.9% (15.7 to 71.8) in men and women,
      respectively. The PAs in 1995/97 were 19.8% (0.2 to 40.2) and 55.1% (21.3 to
      72.8). CONCLUSIONS: In 1995/97 the burden of obesity associated with less than
      third level education was 20% in men and 55% in women aged 25 to 64 years.
      Between 1987 and 1997 the obesity prevalence proportion associated with less than
      third level education increased in women and decreased in men.

PMID- 12011206
TI  - Hysterectomy and socioeconomic position in Rome, Italy.
AB  - STUDY OBJECTIVE: There exists conflicting evidence regarding the higher risk of
      hysterectomy among women of a lower educational and economic level. This study
      aims to assess whether in Italy socioeconomic level is related to hysterectomy
      undertaken for different medical reasons. DESIGN: An area based index was used to
      assign socieconomic status (SES; four levels defined) to 3141 women (aged 35
      years or older) who underwent a hysterectomy in 1997 and were residing in Rome.
      Data were taken from hospital discharge records. Direct age standardised
      hospitalisation rates by SES level were calculated for overall hysterectomies and
      for those performed for either malignant or non-malignant causes. Statistical
      differences were detected using the ratios of standardised rates and the test for
      linear trend. MAIN RESULTS: The hysterectomy rate was 36.7 per 10 000 women aged
      35 years or more. Hysterectomy for uterine leiomyoma accounted for 41% of all
      operations and was more frequent among women aged 35-49 years than for those aged
      50 years or more (crude rates: 28.6 and 7.7 per 10 000, respectively). The risk
      of hysterectomy was 35% higher for the lowest SES group, compared with the
      highest group. No association was found between SES and hysterectomy rates for
      malignant causes, although less affluent women in age group 35-49 years had 87%
      higher risk of hysterectomy compared with most affluent women. The inverse
      association between SES and hysterectomy rates attributable to non-malignant
      causes was statistically significant for women aged 35-49 years but not for those
      aged 50 years or more. CONCLUSIONS: The inverse relation between hysterectomy and
      SES is largely attributable to benign disorders of the uterus, namely leiomyoma
      and prolapse. More affluent women may have a greater uptake of less invasive
      techniques for removing uterine leiomyoma compared with less affluent women, who
      are more likely to undergo unnecessary hysterectomies irrespective of their
      reproductive age.

PMID- 12011207
TI  - Fracture rates lower in rural than urban communities: the Geelong Osteoporosis
      Study.
AB  - BACKGROUND: Urban and rural communities differ in the incidence of several
      diseases including coronary heart disease and some cancers. Lower hip fracture
      rates among rural than urban populations have been reported but few studies have
      compared rural and urban fractures at sites other than the hip. OBJECTIVE: To
      compare total and site specific fracture rates among adult residents of rural and
      urban communities within the same population. DESIGN AND SETTING: This is a
      population based study on osteoporosis in Australia. All fractures occurring in
      adult residents over a two year period were ascertained using radiological
      reports. The rural and urban areas are in close proximity, with the same medical,
      hospital, and radiological facilities permitting uniform fracture ascertainment.
      MAIN OUTCOME MEASURES: All fracture rates were age adjusted and sex adjusted to
      the Australian population according to the 1996 census of the Australian Bureau
      of Statistics and described as the rate per 10 000 person years. The p values
      refer to the adjusted rate difference. RESULTS: The hip fracture rate (incidence
      per 10 000 person years) was 32% lower (39 v 57, p<0.001), and the total fracture
      rate 15% lower (160 v 188, p=0.004) among rural than urban residents,
      respectively. The lower fracture rates in the rural population were also apparent
      for pelvic fractures. CONCLUSION: In the older rural population, lower fracture
      rates at sites typically associated with osteoporosis suggest environmental
      factors may have a different impact on bone health in this community. If the
      national rate of hip fracture could be reduced to that of the rural population,
      the projected increase in hip fracture number attributable to aging of the
      population could be prevented.

PMID- 12011208
TI  - Milk, dairy products, and coronary heart disease.

PMID- 12011209
TI  - Is housework good for health? Levels of physical activity and factors associated
      with activity in elderly women. Results from the British Women's Heart and Health
      Study.
AB  - OBJECTIVE: To determine the prevalence of achieving new recommended levels of
      physical activity, the types of activity involved, and their determinants among
      elderly British women. DESIGN: National cross sectional survey. PARTICIPANTS:
      2341 women aged 60 to 79 from 15 British towns. MAIN OUTCOME MEASURES: Prevalence
      of subjects achieving recommended levels of physical activity. RESULTS: Over two
      thirds of the participants were active at new recommended levels. This was mainly
      achieved through participation in heavy housework. If domestic activities were
      excluded only 21% were regularly active. Women who participated in brisk walking
      for at least 2.5 hours per week had reduced odds of being overweight: odds ratio
      (95% confidence intervals) 0.5 (0.3 to 0.6) after adjustment for other forms of
      activity, health status, smoking, and socioeconomic position. Participating in at
      least 2.5 hours of heavy housework was not associated with reduced odds of being
      overweight 1.1 (0.8 to 1.4). Age, self reported poor health status, coronary
      heart disease, and respiratory disease were independently associated with reduced
      odds of participating in all types of activity. In addition participation in
      brisk walking and physical exercise were less likely in current smokers, those
      from the lowest socioeconomic class, and those living in the north of the
      country. Participation in heavy housework was less likely in women reporting
      depression but was not associated with smoking, socioeconomic class, or area of
      residence. CONCLUSIONS: If new physical activity recommendations, which include
      domestic activities, are used to assess population levels of physical activity
      then it seems that the majority of elderly women are sufficiently active. Heavy
      housework is not associated with reduced levels of being overweight and
      prospective studies are necessary to demonstrate an independent health benefit of
      participating in domestic activities.

PMID- 12011210
TI  - Diabetes mellitus, family history, and colorectal cancer.

PMID- 12011211
TI  - Can ICAM modulation prevent lung injury from ionizing radiation?

PMID- 12011212
TI  - Adenovirus gene therapy for ovarian cancer.

PMID- 12011213
TI  - New uniform population standard better reflects U.S. cancer burden.

PMID- 12011215
TI  - Health agencies adopt new disease classification codes.

PMID- 12011216
TI  - Stat bite: cancer mortality rates age-adjusted by different age standards, 1973
      1999.

PMID- 12011217
TI  - When scientists don't share: is secrecy a necessary evil?

PMID- 12011218
TI  - Cancer survivors still struggle to get adequate follow-up care.

PMID- 12011219
TI  - U.K. Initiative to boost translational research.

PMID- 12011222
TI  - Therapeutic challenges of AIDS-related non-Hodgkin's lymphoma in the United
      States and East Africa.
AB  - Non-Hodgkin's lymphoma (NHL) remains the second most common malignant
      complication in patients with human immunodeficiency virus (HIV) infection. As we
      enter the third decade of the acquired immunodeficiency syndrome (AIDS) epidemic,
      it is apparent that the evolution of antiretroviral therapy and the emergence of
      combination antiviral strategies have greatly affected the natural history of HIV
      infection and its neoplastic complications. For example, there may be a trend for
      declining incidence of AIDS-related lymphoma in the United States for the first
      time. However, in regions of the world where the burden of HIV infection is
      greatest, such as in East Africa, AIDS-related lymphoma is an increasing cause of
      morbidity and mortality. Treatment of lymphoma has evolved coincident with
      improvements in antiretroviral therapy. Infusional chemotherapy regimens may
      offer advantages over other regimens and schedules, but comparative trials have
      not been done. Clinical trial data are available on which to develop therapeutic
      strategies to treat this disease in East Africa where pragmatic approaches are
      needed. Both the differences in manifestations of HIV infection and the inherent
      difficulties in administering cytotoxic chemotherapy in this part of the world
      must be taken into consideration in planning therapeutic strategies. Improved
      understanding of the pathogenesis of HIV infection and lymphoma will likely yield
      improved therapeutic interventions as well.

PMID- 12011223
TI  - Effects of intercellular adhesion molecule 1 (ICAM-1) null mutation on radiation
      induced pulmonary fibrosis and respiratory insufficiency in mice.
AB  - BACKGROUND: Therapy-induced inflammation and progressive fibrosis limit the
      efficacy of thoracic radiotherapy for lung neoplasms. However, mice bearing a
      null mutation of intercellular adhesion molecule 1 (ICAM-1) have previously been
      found to display no inflammatory cell infiltration into the lung following
      thoracic irradiation. We investigated the role of ICAM-1-mediated inflammation in
      the pathogenesis of radiation-induced pulmonary fibrosis in mice with a
      homozygous null mutation in the ICAM-1 gene (ICAM-1(-/-)) and in wild-type mice
      (ICAM-1(+/+)). METHODS: Groups of 10 mice were each irradiated with total doses
      of 12.5, 14, 16, 17, or 18 Gy to the thorax or were mock irradiated. Inflammatory
      cell infiltration was measured by immunohistochemical staining of lung sections
      for leukocyte-common antigen (LCA). Dynamic pulmonary compliance was determined
      by plethysmography. Pulmonary fibrosis was evaluated by measuring alveolar septal
      wall thickness and the hydroxyproline content of lungs by immunohistochemical
      staining of lung sections for collagen III and by Masson's trichrome staining of
      lung sections. All statistical tests were two-sided. RESULTS: Lungs of irradiated
      ICAM-1(-/-) mice had statistically significantly fewer LCA-positive cells than
      the lungs of irradiated ICAM-1(+/+) mice at all radiation doses (P<.001). ICAM-1(
      /-) mice had a higher mean dynamic pulmonary compliance than ICAM-1(+/+) mice
      following irradiation. The incidence of respiratory insufficiency 18 months after
      thoracic irradiation was statistically significantly lower in ICAM-1(-/-) mice
      than in ICAM-1(+/+) mice (odds ratio = 0.19 [95% confidence interval = 0.06 to
      0.58], overall P =.0036). ICAM-1(-/-) mice had less pulmonary fibrosis and
      reduced thickening of the alveolar septum following thoracic irradiation than did
      ICAM-1(+/+) mice. The lungs of irradiated ICAM-1(-/-) mice had less
      hydroxyproline than did the lungs of irradiated ICAM-1(+/+) mice (P =.04).
      CONCLUSIONS: ICAM-1 and inflammation contribute to pulmonary fibrosis and
      impaired pulmonary compliance following thoracic irradiation. Agents that block
      ICAM-1 function or expression should be studied for their effects on the
      prevention of radiation-induced pulmonary fibrosis.

PMID- 12011224
TI  - In vivo molecular chemotherapy and noninvasive imaging with an infectivity
      enhanced adenovirus.
AB  - BACKGROUND: Adenovirus-based gene therapy is a promising approach to treat
      advanced cancers that are resistant to other treatments. However, many primary
      cells lack the requisite coxsackie-adenovirus receptor (CAR), limiting the in
      vivo efficacy of gene therapy. Recently, a modified adenovirus that is not
      dependent on CAR expression for infectivity was developed. We used noninvasive
      imaging to investigate the in vivo antitumor efficacy of gene therapy using this
      adenovirus in an animal model of ovarian cancer. METHODS: The adenoviral vectors
      RGDTKSSTR (CAR-independent) and AdTKSSTR (CAR-dependent) express herpes simplex
      virus thymidine kinase (TK) for molecular chemotherapy and the human somatostatin
      receptor subtype 2 (SSTR) for noninvasive nuclear imaging. Subcutaneous or
      peritoneal human xenograft ovarian cancers were established from highly
      aggressive SKOV3.ip1 cells in immune-deficient mice. Adenoviral constructs were
      infected intratumorally or intraperitoneally once a day for 3 days. Control mice
      received three injections, one per day, of Ad5Luc1, a CAR-dependent adenoviral
      vector that includes a luciferase marker gene. The somatostatin analogue (99m)Tc
      P2045 was used for noninvasive in vivo imaging of RGDTKSSTR that was injected
      into subcutaneous tumors. For mice with peritoneal tumors, survival was compared
      among the different treatment groups using Kaplan-Meier analysis with the log
      rank statistic. All statistical tests were two-sided. RESULTS: Tumor-associated
      RGDTKSSTR could be detected 15 days after introduction of the vector. In the
      subcutaneous model, tumors injected with RGDTKSSTR were statistically
      significantly smaller than those injected with AdTKSSTR (P<.001). In the
      intraperitoneal model, mice treated with RGDTKSSTR lived longer (survival at day
      45 = 63.6%; 95% confidence interval [CI] = 35.2% to 92.0%) than those treated
      with AdTKSSTR (survival at day 45 = 0%) or Ad5Luc1 (survival at day 45 = 18.1%;
      95% CI = 0.0% to 41.0%). DISCUSSION: RGDTKSSTR shows antitumor efficacy against
      ovarian cancer in vivo in animal models. The virus can be imaged noninvasively
      and may have the potential to be a useful agent for treating ovarian cancer.

PMID- 12011225
TI  - Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a
      prospective study of men in China.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) stimulates cell proliferation
      and inhibits apoptosis in the lung and other tissues by interacting with the IGF
      I receptor. The major binding protein for IGF-I, insulin-like growth factor
      binding protein 3 (IGFBP-3), modulates the effects of IGF-I but also inhibits
      cell growth and induces apoptosis independent of IGF-I and its receptor. In a
      prospective study of men in Shanghai, China, we examined the association between
      serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer.
      METHODS: From 1986 to 1989, serum was collected from 18,244 men aged 45-64 years
      living in Shanghai without a history of cancer. We analyzed IGF-I and IGFBP-3
      levels in serum from 230 case patients who developed incident lung cancer during
      follow-up and from 740 control subjects. RESULTS: Among 230 case patients and 659
      matched control subjects, increased IGF-I levels were not associated with
      increased risk of lung cancer. However, for subjects in the highest quartile
      relative to the lowest quartile of IGFBP-3, the odds ratio (OR) for lung cancer,
      adjusted for smoking and IGF-I, was 0.50 (95% confidence interval [CI] = 0.25 to
      1.02). When the analysis was restricted to ever smokers (184 case patients and
      344 matched control subjects), the OR for lung cancer in men in the highest
      quartile of IGFBP-3 relative to those in the lowest quartile, adjusted for
      smoking and IGF-I, was 0.41 (95% CI = 0.18 to 0.92). CONCLUSIONS: In this
      prospective study of Chinese men, higher serum levels of IGF-I did not increase
      the risk of lung cancer. However, subjects with higher serum levels of IGFBP-3
      were at reduced risk of lung cancer. This finding is consistent with experimental
      data that indicate that IGFBP-3 can inhibit cellular proliferation and induce
      apoptosis independent of IGF-I and the IGF-I receptor.

PMID- 12011226
TI  - DNA methylation and environmental exposures in human hepatocellular carcinoma.
AB  - BACKGROUND: Hypermethylation of a CpG-rich promoter (CpG island) blocks
      expression of the corresponding gene. The CpG island methylator phenotype (CIMP),
      defined as a variable pattern of hypermethylation of CpG islands in tumor
      suppressor genes, may be associated with carcinogenesis. To determine whether
      CIMP is associated with the development of hepatocellular carcinoma (HCC) and
      with exposure to environmental agents, we examined the methylation status of CpG
      islands in HCCs from countries with various HCC risks. METHODS: We examined the
      methylation status of 12 CpG islands (eight for known genes) in 85 HCC tumors
      from various geographic locations by use of bisulfite-polymerase chain reaction
      methylation assays and analyzed results with univariate and multivariable
      methods. All statistical tests were two-sided. RESULTS: Eight CpG islands were
      hypermethylated. The frequency of hypermethylation in the 85 tumors was 62% for
      the estrogen receptor (ER), 42% for p16, 18% for cyclooxygenase-2, 21% for the T
      type calcium channel gene, 38% for MINT31, 28% for MINT1, 15% for MINT27, and 11%
      for MINT2 (the latter four CpG islands are not yet associated with genes).
      Methylation levels of the eight frequently methylated CpG islands were positively
      correlated (from R =.2 [P =.05] to R =.6 [P<.001]), supporting the presence of
      CIMP. p16 methylation had statistically significant geographic variation (34.4%
      in tumors from China and Egypt versus 12.2% in tumors from the United States and
      Europe, difference = 22.2%; 95% confidence interval [CI] = 11.2% to 33.2%;
      P<.001). Similar geographic variations were observed for ER methylation and CIMP.
      This observation was partly related to higher methylation in tumors from patients
      with cirrhosis (33.6% for patients with cirrhosis versus 11.7% for those without
      it; difference = 21.9%; 95% CI = 10.9% to 32.8%; P<.001) or hepatitis (34.2% for
      patients with hepatitis versus 6.2% for those without it; difference = 28%; 95%
      CI = 18.3% to 37.6%; P<.001). CONCLUSION: Geographic variations in the
      methylation status of various CpG islands indicate that environmental factors may
      influence the frequent and concordant degree of hypermethylation in multiple
      genes in HCC tumors.

PMID- 12011227
TI  - Regression of tumor growth and induction of long-term antitumor memory by
      interleukin 12 electro-gene therapy.
AB  - BACKGROUND: Interleukin 12 (IL-12) is a proinflammatory cytokine with antitumor
      activity. Plasmid-based intratumoral gene therapy for treating malignancy with IL
      12 or other genes is safe, inexpensive, and simple to carry out. However,
      effective delivery methods for injecting DNA plasmid into a tumor to generate
      therapeutic levels of gene product are lacking. To overcome this obstacle, we
      used electroporation to deliver the IL-12 gene intratumorally in a murine
      squamous cell carcinoma (SCC) model, SCCVII. METHODS: Plasmids with or without
      mouse IL-12 gene were injected into SCCVII tumors of C3H/HeJ mice (n = 5 per
      group). Electric pulses were then applied to the tumors, a process termed electro
      gene therapy. The first treatment was administered when the tumor reached 4-6 mm
      in diameter, and the second treatment followed a week later. The tumor size,
      survival, and ability to generate systemic antitumor memory were assessed at
      various time intervals. Changes in gene expression were measured using northern
      blot analysis, and vessel density and T-cell infiltration were examined by
      immunostaining. The results were analyzed by two-sided Student's t tests.
      RESULTS: Electroporation of 20 microg or 40 microg of IL-12 DNA plasmid
      eradicated tumors in 40% of mice (P =.031 and.022, respectively). A total of six
      mice from two separate experiments with regressed tumors were challenged with
      homologous SCCVII tumor cells multiple times; three of six mice showed no tumor
      growth for more than 11 months and thus indicated the generation of antitumor
      memory in these mice. IL-12 electro-gene therapy was associated with increased
      expression of IL-12, interferon-gamma, monokine induced by interferon-gamma, and
      interferon-inducible protein 10. IL-12 electro-gene therapy was also associated
      with decreased vessel density and increased infiltration of CD8(+) T cells after
      the second administration (P =.02 and.03, respectively). CONCLUSION: IL-12
      electro-gene therapy appears to be effective in reducing tumor growth by
      triggering both antiangiogenic effects and an immune response. The antitumor
      memory was seen to last more than 11 months. Because IL-12 electro-gene therapy
      is easy to administer and is effective, it could potentially be applicable in the
      treatment of electrode-accessible malignancies, such as head and neck SCCs.

PMID- 12011228
TI  - High rate of consent to bank biologic samples for future research: the Eastern
      Cooperative Oncology Group experience.
AB  - The Eastern Cooperative Oncology Group (ECOG) requires patient consent for the
      storage and future use of samples left over from its therapeutic cancer clinical
      trials. The ECOG consent instrument evolved from a simple statement requiring a
      signature to a more detailed three-question format. Between February 1998 and
      October 2000, more than 7000 patients were accrued to studies using one of the
      two consent forms. We analyzed our consent response data by consent type,
      demographic information, disease site, and institution type to determine the
      assent rates for future storage and research on biologic samples and to identify
      possible factors predicting patient refusal. The assent rate for the original
      banking consent statement was 89.4%, whereas that for the more detailed consent
      form was 93.7%. Higher assent rates were statistically significant for the
      detailed consent form versus the original consent form (P=.001), for community
      based practices versus academic centers (P<.001), and for patients aged at least
      65 years versus those younger (P=.002). The results show that increased patient
      protection does not result in decreased availability of biologic samples for
      future research purposes.

PMID- 12011229
TI  - Re: DNA repair, dysplastic nevi, and sunlight sensitivity in the development of
      cutaneous malignant melanoma.

PMID- 12011230
TI  - Hiccups as an adverse reaction to cancer chemotherapy.

PMID- 12011232
TI  - Re: Genetic analysis of the beta-tubulin gene, TUBB, in non-small-cell lung
      cancer.

PMID- 12011233
TI  - Re: genetic analysis of the beta-tubulin gene, TUBB, in non-small-cell lung
      cancer.

PMID- 12011235
TI  - MICROANATOMY, ULTRASTRUCTURE, AND SYSTEMATIC SIGNIFICANCE OF THE EXCRETORY SYSTEM
      AND MANTLE CAVITY OF AN ACOCHLIDIAN GASTROPOD (OPISTHOBRANCHIA).
AB  - The microanatomy and ultrastructure of the excretory system of an undescribed
      mesopsammic gastropod of the genus Hedylopsis have been examined by means of
      semithin serial sections, reconstructions, and transmission electron microscopy.
      The functional metanephridial system comprises a monotocardian heart with a
      single ventricle and auricle in a spacious pericardium as well as a single, large
      kidney. Podocytes in the auricular epicardium represent the site of
      ultrafiltration and formation of the primary urine, whereas the flat epithelium
      of the kidney with extensive basal infoldings, large vacuoles and the apical
      microvillous border indicates modification of the primary filtrate. Solitary
      rhogocytes (pore cells) represent additional loci of ultrafiltration with an
      identical fine-structure as those of the podocytes (meandering slits with
      diaphragms covered by extracellular matrix). The presence of podocytes situated
      in the epicardial wall of the auricle is regarded as plesiomorphic for the
      Opisthobranchia and is confirmed for the Acochlidia for the first time. Kidney
      and rectum both open into a small, yet distinct mantle cavity. Within the
      Acochlidia this condition represents a plesiomorphic character only known from
      one further Hedylopsis species until now. Special cells (here termed microvillous
      pit-cells) with a presumed absorptive function are interspersed between the
      epithelial cells of the mantle cavity. They are mainly characterized by a
      prominent invagination of the apical border with densely arranged, very large
      microvilli. The presence of a mantle cavity that has been lost in all other
      acochlidian genera supports the systematic placement of the Hedylopsidae at the
      base of the Achochlidia.

PMID- 12011236
TI  - COMPARISON OF BIOCHEMICAL COMPOSITION AND DEVELOPMENTAL MODE IN TWO POPULATIONS
      OF COSTASIELLA [OPISTHOBRANCHIA: ASCOGLOSSA (= SACOGLOSSA)].
AB  - Egg masses of two populations of the ascoglossan Costasiella with different
      developmental modes were examined. Costasiella ocellifera is an encapsulated
      developer; Costasiella sp. has an obligate plankto-trophic larval stage. Adults
      of the two populations were also separable by habitat, but could not be
      distinguished by external morphology. Comparison of capsule diameters and
      calorimetric analyses showed that C. ocellifera eggs have nearly eight times the
      capsule volume and 10 times the calories of eggs of its congener. Histochemical
      examination of extra-embryonic intra-capsular vesicles of C. ocellifera revealed
      the contents to be glycoprotein. No inclusions were visible in the capsular fluid
      of Costasiella sp. Egg masses from the two populations differed significantly in
      the amount of TCA-soluble carbohydrate, lipid, and NaOH-soluble protein per egg
      and per milligram dry weight of egg mass. These components were, however, similar
      when expressed on an ash-free dry-weight basis. The advantage of hatching
      directly onto a suitable food source that is temporally persistent, but patchily
      distributed might have provided the selective pressure to achieve extended intra
      capsular development in C. ocellifera.

PMID- 12011237
TI  - COMPARATIVE SPERM ULTRASTRUCTURE OF BAIKALIAN ENDEMIC PROSOBRANCH GASTROPODS.
AB  - Mature euspermatozoan ultrastructure is described for seven species of the
      rissooidean family Baicaliidae (endemic to Lake Baikal, Russia)-Liobaicalia
      stiedae, Teratobaikalia ciliata, T. macrostoma, Baicalia carinata, Pseudobaikalia
      pulla, Maackia bythiniopsis, M. variesculpta, and M. herderiana. For comparison
      with these species and previously investigated Rissooidea, two species of the
      Lake Baikal endemic genus Benedictia (B. cf. fragilis and B. baicalensis;
      Hydrobiidae: Benedictiinae of some authors, Benedictiidae of other authors) in
      addition to Lithoglyphus naticoides (Hydrobiidae: Lithoglyphinae) and Bythinella
      austriaca (Hydrobiidae: Bythinellinae) were also investigated. Paraspermatozoa
      were not observed in any of the species examined, supporting the view that these
      cells are probably absent in the Rissooidea. In general, the euspermatozoa of all
      species examined resemble those of many other caenogastropods (basally
      invaginated acrosomal vesicle, mid-piece with 7-13 helical mitochondria, an
      annulus, glycogen piece with nine peri-axonemal tracts of granules). However, the
      presence of a completely flattened acrosomal vesicle and a specialized peri
      axonemal membranous sheath (a scroll-like arrangement of 4-6 double membranes) at
      the termination of the mid-piece, clearly indicates a close relationship between
      the Baicaliidae and other rissooidean families possessing these features
      (Bithyniidae, Hydrobiidae, Pyrgulidae, and Stenothyridae). Euspermatozoa of
      Benedictia, Lithoglyphus, Bythinella, and Pyrgula all have a solid nucleus, which
      exhibits a short, posterior invagination (housing the centriolar complex and
      proximal portion of the axoneme). Among the Rissooidea, this form of nucleus is
      known to occur in the Bithyniidae, Hydrobiidae, Truncatellidae, Pyrgulidae,
      Iravadiidae, Pomatiopsidae, and Stenothyridae. In contrast, the euspermatozoa of
      the Baicaliidae all have a long, tubular nucleus, housing not only the centriolar
      derivative, but also a substantial portion of the axoneme. Among the Rissooidea,
      a tubular nuclear morphology has previously been seen in the Rissoidae, which
      could support the view, based on anatomical grounds, that the Baicaliidae may
      have arisen from a different ancestral source than the Hydrobiidae. However, the
      two styles of nuclear morphology (short, solid versus long, tubular) occur widely
      within the Caenogastropoda, and sometimes both within a single family, thereby
      reducing the phylogenetic importance of nuclear differences within the
      Rissooidea. More significantly, the occurrence of the highly unusual membranous
      sheath within the mid-piece region in the Baicaliidae appears to tie this family
      firmly to the Bithyniidae + Hydrobiidae + Stenothyridae + Pyrgulidae assemblage.
      Eusperm features of Benedictia spp. strongly resemble those of hydrobiids and
      bithyniids, and neither support recognition of a distinct family Benedictiidae
      (at best this is a subfamily of Hydrobiidae) nor any close connection with the
      hydrobiid subfamily Lithoglyphinae.

PMID- 12011238
TI  - INTRODUCED LAND SNAILS AND SLUGS IN COLOMBIA.
AB  - Twelve species of introduced land molluscs, including seven slug species, have
      been found in the cold zone above 2000 m altitude in the Departamentos
      Cundinamarca and Boyaca, and the Distrito Especial in Colombia. The introduced
      land molluscs remain generally restricted to disturbed environments, from which
      native species are often absent. Most recorded species originated from Europe.
      Deroceras laeve has been present in Colombia for more than a century, whereas the
      other species are probably more recent introductions. The records of Boettgerilla
      pallens, which is indigenous to the Caucasus and has spread over Europe only
      during the last decades, demonstrates that the process of introduction of alien
      molluscs is continuing.

PMID- 12011239
TI  - COMPARATIVE SPERM ULTRASTRUCTURE IN FIVE GENERA OF THE NUDIBRANCH FAMILY
      CHROMODORIDIDAE (GASTROPODA: OPISTHOBRANCHIA).
AB  - Sperm ultrastructure is examined in representatives of five genera of the
      nudibranch gastropod family Chromodorididae: (Chromodoris, Hypselodoris,
      Glossodoris, Risbecia and Pectenodoris) and the results compared with previous
      work on other gastropods, especially other nudibranchs. As chromodoridid
      phylogeny is still incompletely understood, this study partly focuses on the
      search for new and as yet untapped sources of informative characters. Like
      spermatozoa of most other heterobranch gastropods, those of the Chromodorididae
      are elongate, complex cells composed of an acrosomal complex (small, rounded
      acrosomal vesicle, and columnar acrosomal pedestal), a condensed nucleus, sub
      nuclear ring, a highly modified mid-piece (axoneme + coarse fibres surrounded by
      a glycogen-containing, helically-coiled mitochondrial derivative) and terminally
      a glycogen piece (or homologue thereof). The finely striated acrosomal pedestal
      is a synapomorphy of all genera examined here, but interestingly also occurs in
      at least one dorid (Rostanga arbutus). Substantial and potentially taxonomically
      informative differences were also observed between genera in the morphology of
      the nucleus, the neck region of the mid-piece, and also the terminal glycogen
      piece. The subnuclear ring is shown for the first time to be a segmented, rather
      than a continuous structure; similarly, the annular complex is shown to consist
      of two structures, the annulus proper and the herein-termed annular accessory
      body.

PMID- 12011240
TI  - A NEW SPECIES OF DIAPHANA FROM BATHYAL DEPTHS IN THE WEDDELL SEA, ANTARCTICA AND
      FIRST RECORD OF DIAPHANA INFLATA (STREBEL, 1908) IN THE HIGH ANTARCTIC
      (GASTROPODA: OPISTHOBRANCHIA).
AB  - Diaphana haini n.sp. is described from Antarctica. With a depth range from about
      400 to 2100 m, D. haini is the second Antarctic species of this genus to extend
      into the deep sea, the other being D. inflata (Strebel, 1908). Phylogenetic
      analysis has allowed D. haini to be incorporated within Schiotte's (1998)
      cladogram for this genus and, thereby clarify its historical zoogeography. A
      record of D. inflata from the Weddell Sea extends its known distribution range.
      The recorded geographic distribution now ranges from South Georgia to the
      Antarctic continent, and the depth range is extended considerably, from 252-310 m
      to 1645 m.

PMID- 12011241
TI  - THE KINETIC CONGLUTINATE OF THE CREEPER FRESHWATER MUSSEL, STROPHITUS UNDULATUS
      (SAY, 1817).
AB  - The conglutinate of the creeper, Strophitus undulaus (Say, 1817) (Unionoidea:
      Unionidae), was studied with light and scanning electron microscopy. This
      conglutinate has a very simple structure consisting of a homogeneous, spongy
      material containing the glochidia. Each glochidium is contained within its egg
      membrane and is tethered to this membrane by the glochidial thread. Within the
      female's marsupium, the glochidia are contained within the conglutinate. When
      they are expelled to the water the glochidia emerge through pores to the outside
      and become infective. The mechanism for pushing the glochidia out of the
      conglutinate is osmotic. The marsupium apparently bathes the conglutinates in a
      hypertonic solution. When conglutinates are expelled to the surrounding hypotonic
      water, the spongy material of the conglutinate swells, pushing the glochidia out
      through the pores. Unlike other conglutinates studied, that of S. undulatus
      displays a brief period of innate motion which may be adaptive in attracting a
      suitable host.

PMID- 12011242
TI  - MORPHOLOGICAL AND MOLECULAR CHANGES DURING METAMORPHOSIS IN UTTERBACKIA
      IMBECILLIS (BIVALVIA: UNIONIDAE).
AB  - This study examines morphological and biochemical changes that occur as glochidia
      larvae of the freshwater mussel Utterbackia imbecillis (Say, 1829) metamorphose
      into juveniles. Metamorphosis encompasses two distinct stages. The first occurs
      during the first 3-4 days, and involves degeneration of the single larval
      adductor muscle and formation of the characteristic mushroom body by the larval
      mantle cells. These morphological changes are accompanied by an increase in DNA,
      RNA, and protein synthesis. The second stage occurs during the final 4 days of
      the metamorphic period and involves formation of the major anatomical structures
      and organ systems of the juveniles. This stage also is accompanied by an increase
      in DNA, RNA, and protein synthesis. The de novo development of the juvenile
      adductor muscles is described, and sites of DNA, RNA, and protein synthesis are
      identified.

PMID- 12011243
TI  - THE PHYSICAL AND CHEMICAL MICROSTRUCTURE OF THE ACHATINA FULICA EPIPHRAGM.
AB  - Microstructural characterization of Achatina fulica Bowdich, 1822 epiphragms and
      mucus secretions was performed to address two questions: what are the structure
      and composition of the reinforcing inorganic phase in the epiphragms, and what
      enables a durable epiphragm to form quickly in comparison to other biomineralized
      materials? Characterization was performed by a combination of light microscopy
      (relying on a variety of contrast modes), wet chemical tests, environmental
      scanning electron microscopy (including the use of energy dispersive X-ray
      analysis to obtain compositional data), and X-ray diffraction. The morphology of
      the inorganic phase promotes mechanical interlocking and presents a large surface
      for binding to the organic matrix. Strong binding occurs between the organic and
      inorganic phases. The inorganic phase adopts the calcite structure; its
      composition is Ca(0.912) Mg(0.088) CO(3). Epiphragms can form quickly because pre
      grown crystals of the inorganic reinforcing phase are co-deposited with the mucus
      matrix. Unlike other biomineralized material, the crystals are not solution-grown
      in situ on an organic template in the final product.

PMID- 12011244
TI  - THE DIET OF PLATYDORIS ARGO (GASTROPODA: NUDIBRANCHIA) AND THE DIETARY
      SPECIALIZATION OF SPONGE EATING DORIDS.
AB  - The diet of the dorid nudibranch Platydoris argo was studied in relation to prey
      availability, and under different environmental conditions to evaluate richness,
      evenness, and plasticity of its diet. In order to assess the availability of
      possible prey, the sponge assemblage at two different habitats was characterized.
      The results showed that P. argo is a relatively specialized benthic carnivore,
      feeding exclusively on spiculated demosponges. However, it has a relatively
      polyphagous diet (16 prey-species) and adapts well to contrasting patterns of
      prey availability at different sites. At the location with lower sponge
      diversity, the diet of P. argo included more prey categories, was more diverse,
      and less selective (lower dietary evenness), foraging preferentially on the most
      frequent resource, Stylopus dujardini. In contrast, at a station with a clearly
      more diverse and abundant sponge assemblage, the diet was more selective, and
      Phorbas tenacior was its principal component. Despite its trophic plasticity, P.
      argo displayed a specialized pattern of resource exploitation in terms of niche
      breadth within a given habitat. Foraging was focussed on one preferred prey
      (which changed from one habitat to another) as indicated by the significant
      positive selection indexes (S. dujardini = +0.29, P. tenacior = +0.74). The
      revision of quantitative data on the diet of so-called 'sponge eating dorids'
      indicates the existence of a more specialized guild of 'spiculated demosponge
      eating dorids'. Most species revised are 'non-stereotyped specialist', which
      indicates that they have a polyphagous and plastic diet but only exploit one or
      few main prey species in each habitat. However, obligate specialists, with a
      monophagous (or rather oligophagous) diet also seem to be present.

PMID- 12011245
TI  - OOCYTE DEGENERATION AND ALTERED OVIPOSITORY ACTIVITY INDUCED BY PARAQUAT IN THE
      FRESHWATER SNAIL PHYSA FONTINALIS (GASTROPODA: PULMONATA).
AB  - The freshwater snail Physa fontinalis was used as a bioindicator to study the
      effects of the herbicide Paraquat (PQ) in laboratory assays. The test solutions
      used, 0.125, 0.25, and 0.5 mg/l PQ, were in the range of the concentrations
      recommended for aquatic weed control. The study was carried out in two stages to
      determine the influence of PQ on the ovipository activity of Physa fontinalis,
      and the histological effects on these snails. Specimens exposed to PQ continued
      to be reproductively active, but the number of egg masses and eggs laid decreased
      significantly. Mortality was almost the same in all the experimental lots, but
      was significantly related to the production of egg masses only in the controls.
      The histological analysis showed a clear trend among PQ concentrations and
      degenerating oocytes, but no visible effects on the male sex-line were observed.
      By interfering with fertility, PQ has an action that may go well beyond its
      lethal effect on individuals, suggesting that this herbicide should be strictly
      regulated in weed control programmes. Moreover, since PQ was observed to
      interfere with the reproductive process, its endocrine disrupting action must not
      be excluded.

PMID- 12011246
TI  - Holothurian feeding by Nassarius dorsatus on a beach in Western Australia.

PMID- 12011247
TI  - Molecular characterization of the bivalves Mya arenaria, Mya truncata and
      Hiatella arctica.

PMID- 12011248
TI  - The use of electrical-component freezing spray as a method of killing and
      preparing snails.

PMID- 12011249
TI  - Development of the sperm storage organ in Arianta arbustorum (Stylommatophora:
      Helicidae).

PMID- 12011251
TI  - MICROANATOMY, ULTRASTRUCTURE, AND SYSTEMATIC SIGNIFICANCE OF THE EXCRETORY SYSTEM
      AND MANTLE CAVITY OF AN ACOCHLIDIAN GASTROPOD (OPISTHOBRANCHIA).

PMID- 12011250
TI  - Laboratory experiments on snail-size selection by a snail predator, Sargochromis
      codringtoni (Pisces: Cichlidae).

PMID- 12011252
TI  - Intragenic PTEN/MMAC1 loss of heterozygosity in conventional (clear-cell) renal
      cell carcinoma is associated with poor patient prognosis.
AB  - Inactivation of the PTEN/MMAC1 tumor suppressor gene has been linked to tumor
      progression in several human malignancies. However, the role of PTEN/MMAC1 in the
      development and progression of the major renal cell carcinoma morphotypes remains
      controversial. We examined microdissected specimens from 80 conventional (clear
      cell) renal cell carcinomas (cRCC), 27 papillary renal cell carcinomas (pRCC),
      and 16 chromophobe renal cell carcinomas (chRCC) for loss of heterozygosity (LOH)
      at and around the PTEN/MMAC1 locus and for mutations in the PTEN/MMAC1 gene. The
      results of the molecular studies were correlated with tumor stage, grade, and
      patient survival. LOH at one or more of the examined loci occurred in 37.5% of
      cRCC, 29.6% of pRCC and 87.5% of chRCC specimens. The chRCC specimens showed
      increasing rates of LOH the further that a marker was located toward the q
      telomer of chromosome 10, consistent with nonspecific genetic disarray in
      genomically highly unstable tumors. No such pattern was discernible in the cRCC
      and pRCC. In the cRCC, LOH at intragenic PTEN/MMAC1 microsatellite markers
      (indicating deletional events involving the actual PTEN/MMAC1 gene) was
      significantly associated with tumor death, with 85.7% of such patients dying,
      whereas only 45.3% of patients without intragenic LOH died (P =.018). There were
      no PTEN/MMAC1 mutations in our specimens. We conclude that PTEN/MMAC1
      inactivation may play a role in the progression of cRCC. Biallelic inactivation
      may preferentially occur by nonmutational mechanisms, or, alternatively,
      haploinsufficiency of PTEN/MMAC1 may be sufficient to affect tumor progression in
      cRCC.

PMID- 12011253
TI  - Topoisomerase II-alpha expression in different cell cycle phases in fresh human
      breast carcinomas.
AB  - Topoisomerase II-alpha (topo II alpha) is the key target enzyme for the
      topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo II
      alpha is expressed predominantly in the S/G2/M phase of the cell cycle. In
      malignant cells, in vitro studies have indicated that the expression of topo II
      alpha is both higher and less dependent on proliferation state in the cell. We
      studied fresh specimens from 50 cases of primary breast cancer. The expression of
      topo II alpha in different cell cycle phases was analyzed with two-parameter flow
      cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The
      expression of topo II alpha was significantly higher in the S/G2/M phase of the
      cell cycle than in the G0/G1 phase in both DNA diploid and DNA non-diploid
      tumors. In 18 of 21 diploid tumors, and in 25 of 29 non-diploid tumors, >50% of
      the topo II alpha-positive cells were in the G0/G1 phase. This significant
      expression of topo II alpha in the G0/G1 phase of the cell cycle may have
      clinically important implications for treatment efficacy of topoisomerase II
      inhibitors.

PMID- 12011254
TI  - Lymphoepithelial cysts of the pancreas: a report of 12 cases and a review of the
      literature.
AB  - Lymphoepithelial cyst (LEC) of the pancreas is a rare lesion of undetermined
      pathogenesis that had been documented almost exclusively in males. The literature
      on this entity is limited to reports of single or small numbers of cases. Here is
      presented a clinicopathologic analysis of 12 patients with LEC, 4 of whom were
      female. The mean age of the patients was 56 years. Four patients presented with
      abdominal pain and nausea, but in two patients, the cysts were detected
      incidentally. Only one patient had a history of chronic pancreatitis, and another
      had a family member with pancreatic cancer. In one patient, a clinical diagnosis
      of pseudocyst was rendered, and the remaining patients were clinically thought to
      have cystic neoplasms. None of the patients had any identifiable
      immunosuppression, HIV positivity, autoimmune disorder (such as Sjogren syndrome)
      or lymphoma. Seven cysts were located in the head of the pancreas, and 5 were in
      the tail. The mean size was 4.8 cm (range, 1.2-17 cm). Five LECs were
      multilocular, three were unilocular; in others, the number of loculi was not
      recorded. All were "macrocystic" lesions. Two patients had two separate lesions,
      both in the tail of the pancreas. Histologically, all cases were characterized by
      cysts, some containing keratin, and lined by mature stratified squamous
      epithelium surrounded by dense lymphoid tissue, often with prominent follicles.
      In some areas, the lining epithelium had more cuboidal, flattened, or
      transitional appearance. Mucinous goblet-like cells were seen in one case. Acute
      inflammation was not seen. Four cases contained solid lymphoepithelial islands, a
      feature not previously described in LECs. No squamous metaplasia was identified
      in the uninvolved pancreatic tissue and no epithelial elements were identified in
      peripancreatic lymph nodes. In summary, LEC of the pancreas is a rare but
      distinctive lesion that may be seen in the tail of the organ where most cystic
      pancreatic neoplasms are encountered. In contrast to the impression from the
      literature, LECs may also develop in females and, therefore, should be considered
      in the clinical differential diagnosis of mucinous cystic neoplasms that affect a
      similar age group. LECs are not associated with the clinical syndromes that are
      seen with their analogues in the salivary glands.

PMID- 12011255
TI  - Prognostic significance of fibrotic focus in invasive ductal carcinoma of the
      breast: a prospective observational study.
AB  - We have already reported invasive ductal carcinomas (IDCs) with fibrotic focus
      (FF) to be associated with significantly poorer survival than IDCs without FF.
      The purpose of this study was to prospectively investigate the effect of the
      presence of FF on the outcomes of 439 patients with IDCs to confirm the
      prognostic significance of FF, by the multivariate analysis, employing the Cox
      proportional hazard regression model, as compared with well-known
      clinicopathological parameters. We also precisely evaluated the prognostic
      significance of FF from the viewpoint of FF characteristics. The present study
      demonstrated that the presence of FF is a very useful parameter predicting tumor
      recurrence (TR), as well as initial distant organ metastasis (IDOM), in lymph
      node-negative IDCs (P =.024 and P =.026) and in IDCs positive for either or both
      estrogen receptor (ER) or progesterone receptor (PR) (P =.007 and P =.015),
      respectively. In addition, FF of >8 mm in diameter was found to be an independent
      prognostic parameter for TR and IDOM in lymph node-negative patients and patients
      with IDC positive for either or both ER or PR (P =.005 and P =.018). We conclude
      that the presence of FF is a very important histologic prognostic parameter for
      patients with IDCs of the breast.

PMID- 12011256
TI  - A comparative analysis of FISH, RT-PCR, PCR, and immunohistochemistry for the
      diagnosis of mantle cell lymphomas.
AB  - Mantle cell lymphoma (MCL) diagnosis first relies on morphology and phenotype
      that may overlap with other B-cell lymphomas. Therefore, the demonstration of
      t(11;14)(q13;q32), the cytogenetic hallmark of MCL, is considered of diagnostic
      value. By studying a series of 35 MCL with characteristic morphology and
      phenotype (CD5+, CD10-, CD20+, CD23-), we have evaluated the applicability and
      the sensitivity of interphase fluorescence in situ hybridization (FISH) for
      t(11;14) detection and other techniques: (1) polymerase chain reaction (PCR) for
      amplification of t(11;14) genomic breakpoint, (2) competitive RT-PCR for the
      detection of cyclin D1 transcripts overexpression, and (3) immunohistochemistry
      (IHC) for cyclin D1 protein detection. Tissues from different origins were
      analyzed: lymph nodes (n = 24), spleen (n = 3), digestive biopsy (n = 3), tonsils
      (n = 3), and skin (n = 2). Interphase FISH was performed either on touch
      preparations (n = 11) and frozen (n = 9) or paraffin sections (n = 15). FISH
      analysis detected t(11;14) in 34/35 cases (97%) and demonstrated a recurrent
      CCND1 amplification in t(11;14)+ nuclei of the three blastoid MCL variants of our
      series. Genomic PCR analysis, hampered by the scattering of 11q13 breakpoints,
      was positive in only 13/35 cases (37%). RT-PCR analysis was applicable on
      nonepithelial tissues (27/35) and showed cyclin D1 transcript overexpression in
      all tested cases (27/35). IHC for cyclin D1 protein was performed either on
      frozen (n = 12) or on paraffin sections (n = 23), and its sensitivity was higher
      on paraffin sections (91%) than on frozen sections (25%). A cyclin D1 protein
      immunoreactivity was observed in 24/35 cases (69%). Our study emphasizes on the
      use of FISH analysis for the direct detection of t(11;14) because its
      applicability and sensitivity largely exceeded those of other techniques. It may
      also provide some informations on secondary cytogenetic changes of potential
      clinical relevance.

PMID- 12011257
TI  - Differential involvement of protein 4.1 family members DAL-1 and NF2 in
      intracranial and intraspinal ependymomas.
AB  - Ependymomas are malignant CNS neoplasms with highly variable biologic behavior,
      including a generally better prognosis for intraspinal tumors. Inactivation of
      the NF2 gene on 22q12 and loss of its protein product, merlin, have been well
      documented in subsets of meningiomas and ependymomas. DAL-1, a related tumor
      suppressor and protein 4.1 family member on 18p11.3, has also been recently
      implicated in meningioma pathogenesis, though its role in ependymoma remains
      unknown. Therefore, we evaluated 27 ependymomas (12 intracranial and 15 spinal)
      using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to
      determine NF2/merlin and DAL-1/DAL-1 status at the DNA and protein levels.
      Demonstrable NF2 and DAL-1 gene deletions were each detected in 6 (22%)
      ependymomas. All 5 merlin losses by IHC occurred in spinal ependymomas (P =.047),
      whereas 5 (71%) DAL-1-negative cases were intracranial (P =.185). The former
      result is consistent with prior observations that NF2 mutations are generally
      limited to spinal ependymomas. In contrast to meningiomas, simultaneous merlin
      and DAL-1 losses were not encountered. Our findings suggest that (1) NF2 and DAL
      1 losses are involved in the pathogenesis of spinal and intracranial ependymoma
      subsets, respectively and (2) given the number of cases with no demonstrable
      losses, other cellular perturbations must also be critical for tumori-genesis.

PMID- 12011258
TI  - Melanoma growth stimulatory activity in primary malignant melanoma: prognostic
      significance.
AB  - Malignant melanoma (MM) cells do not require all exogenous growth factors of
      normal melanocytes. It is hypothesized that they make their own growth factors
      including melanoma growth stimulatory activity (MGSA). Cultured melanoma cells
      respond to MGSA with increased growth and angiogenesis suggesting a role for MGSA
      in MM proliferation, differentiation, and progression. We assessed the prognostic
      significance of MGSA expression in 37 primary MM immunostained for MGSA.
      Immunostains were graded for intensity (0-3+), percentage of cells immunostained,
      and location of immunostain (intraepidermal, junctional, or dermal). In addition,
      31 melanocytic and 23 dysplastic nevi were similarly studied for MGSA expression.
      All MM showed the presence of immunostain, 6 (16%) 1+, 12 (32%) 2+, and 19 (51%)
      3+. Six (16%) had immunostain in < or = 50% tumor cells, 31 (84%) in >50%. A
      significant number of MM showed >50% tumor cells staining at the dermal-epidermal
      junction compared with intraepidermal staining (P <.0001). Intensity and amount
      of immunostain did not correlate with Clark's or Breslow's level. During a mean
      follow-up of 60 months (range: 5-101) on 27 patients, there were 4 local
      recurrences, 6 distant metastases, and 10 deaths. MGSA expression was not of
      prognostic significance with regard to survival (overall, disease free), or local
      recurrence or distant metastasis in primary MM. MGSA expression was similar in
      benign melanocytic and dysplastic nevi. Strong diffuse expression was noted in
      the junctional component of all junctional and most compound nevi. The dermal
      component consistently expressed less or no (in 45% of intradermal nevi) MGSA.
      MGSA expression does not correlate with prognosis in MM. Increased expression of
      MGSA at the dermal-epidermal junction in nevi and MM may indicate a role for MGSA
      in early local growth, before development of atypia.

PMID- 12011259
TI  - Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20
      in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases.
AB  - Distinguishing primary pulmonary adenocarcinoma from metastatic adenocarcinoma
      involving the lung is a common challenging task. The distinction between mucinous
      bronchioloalveolar carcinoma (BAC) and metastatic mucinous carcinoma of other
      sites, in particular, is difficult by routine histology. Immunohistochemical
      expression of thyroid transcription factor-1 (TTF-1), as well as cytokeratin 7
      (CK 7) and cytokeratin 20 (CK 20), has proven diagnostic utility in discerning
      primary from metastatic neoplasms in the lung. Rigorous studies assessing the
      expression of these markers in BACs, particularly in regard to nonmucinous and
      mucinous subtypes, have not been performed. In this study, we evaluated the
      immunohistochemical expression of TTF-1, CK 7, and CK 20 in 67 BACs (48
      nonmucinous, 12 mucinous, and 7 of mixed histology). Overall, 42 (63%) of the 67
      BACs were positive for TTF-1. When stratified according to subtype, all 12
      mucinous BACs were observed to be TTF-1 negative. This trend toward absence of
      TTF-1 expression in mucinous areas was also maintained among tumors with mixed
      histology. Sixty-three (94%) of 67 BACs were CK 7 positive, with no differences
      in expression observed upon subtype stratification. Three cases were noted to be
      positive for CK 20; all exhibited mucinous morphology. These results indicate
      that in contrast to the immunophenotypic profile exhibited by most pulmonary
      neoplasms, mucinous BACs are TTF-1 negative and may express CK 20. This suggests
      that in the context of differentiating mucinous BACs from extrapulmonary mucinous
      tumors metastatic to the lung, evaluation of TTF-1 and CK 20 expression may have
      limited diagnostic utility.

PMID- 12011260
TI  - Adenoma versus carcinoid tumor of the middle ear: a study of 48 cases and review
      of the literature.
AB  - Carcinoid tumors and adenomas of the middle ear are rare neoplasms of
      indeterminate relationship to one another. Indeed, the literature is devoid of a
      large comprehensive series that evaluates the clinical, histologic, and
      immunophenotypic features of these tumors and their potential relationship. Forty
      eight cases of middle ear adenoma between 1970 and 1995 were identified in the
      files of the Armed Forces Institute of Pathology. All cases were evaluated for
      cytomorphology and architectural pattern, in addition to their reactivity with
      various immunohistochemical reagents. Clinical follow-up was also obtained. A
      comprehensive review of the literature was performed with an eye toward
      correlating any distinct differences or similarities between carcinoid tumors and
      adenomas of the middle ear. The patients included 21 women and 27 men, aged 20 to
      80 years (mean, 45.0 y). Patients experienced hearing loss, mass, and/or pain for
      a mean duration of 1.7 years. The mean tumor size was 0.8 cm, with six tumors
      extending beyond the middle ear. Histologically, the tumors were moderately
      cellular and unencapsulated, arranged in glandular, trabecular, and solid
      patterns composed of small cells with "salt and pepper" nuclear chromatin
      distribution. The tumor cells were immunoreactive with keratin, keratin 7,
      chromogranin, and human pancreatic polypeptide. All patients had surgery. No
      patients died with their disease (mean follow-up, 15.7 y). Eight patients
      developed recurrences that were treated surgically and were without evidence of
      disease at last follow-up (mean, 15.1 y). Our study and the review of the
      literature showed adenomas and carcinoid tumors of the middle ear to be
      essentially indistinguishable benign tumors. Middle ear adenoma most correctly
      describes their morphologic features and clinical behavior, although
      neuroendocrine adenoma of the middle ear may be a more accurate designation.

PMID- 12011261
TI  - Real-time RT-PCR assay for quantifying cyclin D1 mRNA in B-cell non-Hodgkin's
      lymphomas.
AB  - Mantle cell lymphoma (MCL) is a distinct type of non-Hodgkin's lymphoma (NHL)
      characterized by the t(11;14)(q13;q32), in which the ccnd1 gene is juxtaposed
      with the immunoglobulin heavy chain gene, resulting in up-regulation of cyclin
      D1. Cyclin D1 overexpression is a useful finding that supports the diagnosis of
      MCL. In this study, we used a 5' --> 3' exonuclease-based real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) method to quantify cyclin D1
      mRNA in 108 B-cell NHL and nonneoplastic specimens, including 25 cases of MCL.
      Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also quantified to normalize
      cyclin D1 mRNA levels, and the data were expressed as a cyclin D1 to GAPDH ratio.
      At each anatomic site, MCL cases had higher cyclin D1 levels than other types of
      NHL or nonneoplastic specimens, without overlap. For example, in lymph node
      specimens, the median cyclin D1/GAPDH ratio was 147 (range, 94-160) in MCL,
      compared with 8.6 (range, 4-18) in chronic lymphocytic leukemia/small lymphocytic
      lymphoma; 5.8 (range, 1.8-24) in follicular lymphoma; 4.8 in one case of marginal
      zone lymphoma; and 20.2 (range, 5.8-44) in reactive specimens. Statistical
      analysis using one-way analysis of variance (ANOVA) showed that MCL cases had
      significantly higher cyclin D1 levels than other groups (P <.05). In peripheral
      blood specimens involved by MCL, cyclin D1 levels correlated with extent of
      involvement. We conclude that this real-time RT-PCR method to quantify cyclin D1
      expression is helpful in distinguishing MCL from other types of B-cell NHL and
      from nonneoplastic specimens. This method is rapid, can be applied to the
      analysis of fluid specimens, and obviates the need for time-consuming and
      laborious detection methods that are required by traditional semi-quantitative RT
      PCR methods.

PMID- 12011262
TI  - The utility and cost effectiveness of voice recognition technology in surgical
      pathology.
AB  - Voice recognition (VR) technology in computer systems converts speech directly
      into electronic text. In pathology, VR holds promise to improve efficiency and to
      reduce transcription delays and costs. We investigated the utility and cost
      effectiveness of targeted VR deployment in surgical pathology. A VR system was
      deployed for entry of gross descriptions of biopsies and of low to moderate
      complexity specimens and for entry of final reports for specimens not requiring
      microscopic analysis. Templates for VR were developed for all reports. Free-text
      speech entry was used to enter information not covered by templates. Voice
      converted to text by VR crossed over an interface into the anatomic pathology
      laboratory information system. Tallies were kept of whether individual specimens
      were entered by VR or by conventional dictation. A computer program was written
      to analyze the number of lines of text entered through VR. Cost savings were
      calculated based on per-line transcription costs from an outside agency. Over 18
      months, gross descriptions for an average of 5617 specimens per month were
      entered via VR, corresponding to 70% of all gross specimens processed by the
      laboratory. A mean of 106 gross-only final reports per month was entered through
      VR. VR facilitated same-day processing of specimens received after the previous
      day processing cutoff time (average 35 specimens per day). VR generated an
      average of 23,864 lines of text per month, translating to $2625 savings per
      month. Estimated payback period for VRT as implemented is 1.9 years. The use of
      VR for gross descriptions of biopsies and low to moderate complexity specimens
      and for gross-only final reports in surgical pathology facilitates data entry,
      reduces transcription costs, and contributes to improved turnaround time.
      Development of templates is important to successful implementation of VR in
      surgical pathology.

PMID- 12011263
TI  - Translocation der(13;21)(q10;q10) in skeletal and extraskeletal mesenchymal
      chondrosarcoma.
AB  - Cytogenetic studies of mesenchymal chondrosarcoma are few and to date, no
      specific or recurrent aberrations have been found. In this investigation, the
      cytogenetic and molecular cytogenetic (spectral karyotypic and fluorescence in
      situ hybridization) findings for two mesenchymal chondrosarcomas, one arising
      skeletally and the other extraskeletally, are reported. An identical Robertsonian
      translocation involving chromosomes 13 and 21 [der(13;21)(q10;q10)] was detected
      in both cases, possibly representing a characteristic rearrangement for this
      histopathologic entity. Both cases also exhibited loss of all or a portion of
      chromosomes 8 and 20 and gain of all or a portion of chromosome 12. The
      observation of similar chromosomal abnormalities in both skeletal and
      extraskeletal mesenchymal chondrosarcoma supports a genetic as well as
      histopathologic relationship between these anatomically distinct neoplasms.

PMID- 12011264
TI  - Disseminated microsporidiosis caused by Encephalitozoon cuniculi III (dog type)
      in an Italian AIDS patient: a retrospective study.
AB  - We report a case of disseminated microsporidiosis in an Italian woman with AIDS.
      This study was done retrospectively using formalin-fixed, paraffin-embedded
      tissue specimens obtained at autopsy. Microsporidia spores were found in the
      necrotic lesions of the liver, kidney, and adrenal gland and in ovary, brain,
      heart, spleen, lung, and lymph nodes. The infecting agent was identified as
      belonging to the genus Encephalitozoon based on transmission electron microscopy
      and indirect immunofluorescence. Additional molecular studies, including sequence
      of the rDNA internal transcribed spacer region, identified the agent as E.
      cuniculi, Genotype III. We believe that this is the first report of a human case
      of disseminated microsporidial infection involving the ovary.

PMID- 12011265
TI  - Correspondence re: Aguilera NS, Tomaszewski MM, Moad JC, Bauer FA, Taubenberger
      JK, Abbondanzo SL. Cutaneous follicle center lymphoma: a clinicopathologic study
      of 19 cases. Mod pathol. 2001;14:828-35. and Franco R, Fernandez-Vazquez A,
      Mollejo M, Cruz MA, Camacho FI, Garcia JF, Navarrete M, Piris MA. Cutaneous
      presentation of follicular lymphomas. Mod pathol. 2001;14:913-9.

PMID- 12011266
TI  - Diagnostic challenges in headache: migraine as the wolf disguised in sheep's
      clothing. Introduction.

PMID- 12011267
TI  - The role of concomitant headache types and non-headache co-morbidities in the
      underdiagnosis of migraine.
AB  - That migraine is significantly underdiagnosed in the United States and other
      countries is well established. New data from a follow-up survey to the American
      Migraine Study II reveal that the presence of concomitant headache types and co
      morbid conditions significantly affects the ability to detect and diagnose
      migraine. This article describes these data and explores the contribution of
      concomitant headache types and co-morbidities to the problem of underdiagnosis of
      migraine. Migraine continues to be underdiagnosed because of failure to recognize
      it (missed diagnosis) and because of misdiagnosis of migraine as another headache
      type. First, a diagnosis of migraine may be missed in the presence of other
      headache types that occur proportionally more frequently than migraine and
      thereby overshadow migraine. Second, migraine may be misdiagnosed when health
      care providers inappropriately interpret specific symptoms and co-morbid
      conditions as indicators of the presence of a non-migraine headache type such as
      sinus or tension. By becoming aware of these diagnostic pitfalls and being more
      judicious and deliberate in diagnosing migraine and other headache types, health
      care providers can improve the diagnosis of migraine and help patients to receive
      appropriate therapy.

PMID- 12011268
TI  - Sinus headache or migraine? Considerations in making a differential diagnosis.
AB  - Sinus headache is commonly diagnosed, and patients with headache often cite sinus
      pain and pressure as a cause of their headaches. A high frequency of diagnosis of
      sinus headache, which specialists consider to be relatively rare, among patients
      meeting International Headache Society (IHS) diagnostic criteria for migraine
      raises the possibility that migraine and perhaps other headache types are
      sometimes mistaken for sinus headache. This article considers clinical,
      epidemiologic, and pathophysiologic relationships between sinus headache and
      migraine and discusses the implications for clinical management of headache. Both
      historic and new data show that nasal symptoms frequently accompany migraine,
      although these symptoms are not part of the IHS diagnostic criteria for migraine.
      Parasympathetic activation, as well as the hypothesized mechanism of neurogenic
      or immunogenic switching (i.e., crossover interactions of neurogenic and
      immunogenic inflammation), may account for both the frequent occurrence of nasal
      symptoms in migraine and the possibility that sinus inflammation can sometimes
      act as a migraine trigger. Considered in aggregate, the data show that the
      occurrence of nasal symptoms associated with a headache should neither trigger a
      diagnosis of sinus disease nor exclude a diagnosis of migraine. It should, in
      fact, prompt diagnostic consideration of both conditions.

PMID- 12011269
TI  - Migraine and tension-type headache: an assessment of challenges in diagnosis.
AB  - The difficulty in distinguishing episodic tension-type headache from migraine
      headache is widely acknowledged. The misdiagnosis of migraine as tension-type
      headache has potentially significant consequences because it may preclude
      patients with disabling headaches from receiving appropriate treatment. This
      article explores the symptomatologic, epidemiologic, and pathophysiologic
      relationships among migraine and tension-type headaches with the aim of
      elucidating ways to improve their diagnosis and treatment. Clinical,
      epidemiologic, and pharmacologic data converge to suggest that rigid adherence to
      the IHS criteria in diagnosing migraine and tension-type headache may result in
      misdiagnosis of some headaches. Many migraine attacks are accompanied by tension
      headache-like symptoms, such as neck pain. Conversely, IHS-defined tension-type
      headaches are often accompanied by migraine-like symptoms, such as photophobia or
      phonophobia and aggravation by activity. The health-care provider caring for
      patients with headache should be cognizant of these overlaps and their
      implications for the management of patients with headache.

PMID- 12011270
TI  - Self-awareness of migraine: interpreting the labels that headache sufferers apply
      to their headaches.
AB  - Although people with migraine are aware of their headaches they are often not
      aware that they have migraine. This can lead to inappropriate or ineffective use
      of treatments, delays in seeking appropriate care, and miscommunication during
      clinical encounters. This article assesses self-recognition of migraine and
      identifies terms used by migraine sufferers to describe their migraine headaches.
      Individuals were selected for telephone interview by random digit dialing in
      several large United States cities as a part of a clinical trials recruiting
      initiative. Individuals (n = 30,758) aged 18 to 65 years of age were interviewed
      about their headaches using a validated computer-assisted telephone interview.
      Among the 23,564 respondents who reported headache, their headaches were
      classified as migraine (with or without aura) by the criteria of the
      International Headache Society (IHS). The relationships among the terms subjects
      used for their headaches and their IHS diagnosis of migraine were assessed. Of
      the 23,564 respondents, 4,967 individuals called their headache migraine and
      3,074 individuals reported headache that met the IHS criteria for migraine. The
      positive predictive value for self-assessed migraine is 33.1%; the negative
      predictive value for a self-assessment other than migraine is 92.3%. Therefore,
      individuals who called their headaches migraine were about three times more
      likely to meet IHS criteria for migraine. Among the 3,074 individuals meeting IHS
      criteria for migraine, only 53.4% recognized their headaches as migraine
      (sensitivity 54%; specificity 83.8%). Among migraineurs, stress headaches (n =
      345) and sinus headaches (n = 365) were the most common erroneous labels
      reported. Age influenced the erroneous terminology. Individuals less than 40
      years of age were more likely to misidentify their migraine as stress headaches,
      whereas individuals 40 years of age and older were more likely to misidentify
      their migraines as sinus headaches. In a population sample, 54% of individuals
      with IHS migraine did not know that their headaches are migraine. Those who
      called their headaches migraine were much more likely to have migraine. Migraine
      awareness programs that rely solely on the term "migraine" may miss individuals
      who urgently need to be reached. Therefore, public education should target people
      with severe or disabling headache and aim to create awareness of the diagnostic
      possibilities.

PMID- 12011271
TI  - Diagnostic lessons from the spectrum study.
AB  - Article abstract Migraine is a heterogeneous condition that causes symptoms that
      vary both among individuals and within individuals from attack to attack. We
      examined and reviewed several important lessons on the diagnosis of migraine
      learned from the distribution of headache types and patterns of treatment
      response in the Spectrum Study, including recruitment and diagnostic issues. The
      accuracy of an initial diagnosis, assigned by a clinician in the context of a
      clinical trial, was compared with the results of a final diagnosis, assigned by a
      neurologist, reviewing the initial evaluation as well as headache diaries for up
      to 10 attacks. Several lessons can be learned from the Spectrum Study.
      Recruitment difficulties teach us that disabling tension-type headache is
      difficult to find, suggesting that it is rare. Examination of the final diagnosis
      given after diary evaluations suggests that a diagnosis of migraine can usually
      be confirmed for patients with disabling headache. After reclassification of the
      final sample of 432 subjects, 24/75 (32%) patients initially clinically
      classified as having disabling episodic tension-type headache proved to have
      migraine or migrainous headache after a diary review. Among study participants,
      90% of subjects with disabling headache (HIMQ score >250) had a migraine-related
      disorder. Treatment response suggests that, in migraineurs, tension-type
      headaches may have a pathophysiology similar to that of migraine. The diary data
      show that mild headaches in patients with disabling migraine often evolve into
      full-blown migraine. The Spectrum Study supports the view that, for patients with
      disabling episodic headache, migraine is often the correct diagnosis. In clinical
      practice, the suspicion of migraine should be high for patients experiencing
      episodic disabling headache. Assessment of headache-related disability may assist
      practitioners in making a diagnosis of migraine.

PMID- 12011272
TI  - Assessing the risk of drug-induced neurologic disorders: statins and neuropathy.

PMID- 12011274
TI  - Cannabinoids in MS: potentially useful but not just yet!

PMID- 12011276
TI  - Emergency craniotomy for intracerebral hemorrhage: when doesn't it help and does
      it ever help?

PMID- 12011277
TI  - Statins and risk of polyneuropathy: a case-control study.
AB  - BACKGROUND: Several case reports and a single epidemiologic study indicate that
      use of statins occasionally may have a deleterious effect on the peripheral
      nervous system. The authors therefore performed a population-based study to
      estimate the relative risk of idiopathic polyneuropathy in users of statins.
      METHOD: The authors used a population-based patient registry to identify first
      time-ever cases of idiopathic polyneuropathy registered in the 5-year period 1994
      to 1998. For each case, validated according to predefined criteria, 25 control
      subjects were randomly selected among subjects from the background population
      matched for age, sex, and calendar time. The authors used a prescription register
      to assess exposure to drugs and estimated the odds ratio of use of statins (ever
      and current use) in cases of idiopathic polyneuropathy compared with control
      subjects. RESULTS: The authors verified a diagnosis of idiopathic polyneuropathy
      in 166 cases. The cases were classified as definite (35), probable (54), or
      possible (77). The odds ratio linking idiopathic polyneuropathy with statin use
      was 3.7 (95% CI 1.8 to 7.6) for all cases and 14.2 (5.3 to 38.0) for definite
      cases. The corresponding odds ratios in current users were 4.6 (2.1 to 10.0) for
      all cases and 16.1 (5.7 to 45.4) for definite cases. For patients treated with
      statins for 2 or more years the odds ratio of definite idiopathic polyneuropathy
      was 26.4 (7.8 to 45.4). CONCLUSIONS: Long-term exposure to statins may
      substantially increase the risk of polyneuropathy.

PMID- 12011278
TI  - Resection of the lesion in patients with hypothalamic hamartomas and catastrophic
      epilepsy.
AB  - BACKGROUND: Patients with hypothalamic hamartomas (HH) often have severe
      refractory epilepsy, incapacitating behavioral abnormalities, and cognitive
      decline. Attempts to control the seizure disorder by resection of apparently
      epileptogenic mesial temporal or other cortical structures have failed
      consistently. OBJECTIVE: To report a series of 13 patients in whom the hamartoma
      itself was resected. METHODS: All patients underwent preoperative evaluation
      between ages 2 and 33 years and had subtotal or complete resection of the
      hamartoma. Follow-up ranged from 1 to 5.5 years (mean: 2.8 y). RESULTS:
      Preoperatively, all patients had variable combinations of gelastic, complex
      partial, and generalized seizures. Eight had drop attacks. In addition, all had
      marked behavior abnormalities and cognitive impairment. Postoperatively, two
      patients are completely seizure-free and 11 are either seizure-free or have
      achieved a greater than 90% reduction of drop attacks and generalized tonic
      clonic seizures. However, minor gelastic, complex partial, and atypical absence
      seizures have persisted in 11 patients, although at significantly reduced rates.
      In addition, there has been a dramatic improvement in behavior and cognition.
      Three patients had an anterior thalamic and one a capsular infarct, which left
      only minimal long-term deficits. Exact location of the lesion in relation to the
      interpeduncular fossa and the walls of the third ventricle correlated with extent
      of excision, seizure control, and complication rate. CONCLUSION: Resection can
      alleviate both the seizures and the behavioral and cognitive abnormalities of
      hypothalamic hamartomas, but complications are frequent.

PMID- 12011279
TI  - Effect of antiepileptic drugs on bone density in ambulatory patients.
AB  - BACKGROUND: Long-term antiepileptic drug (AED) use causes multiple abnormalities
      in calcium and bone metabolism that have been most extensively described in
      institutionalized patients. The objective is to determine the effect of AED on
      vitamin D levels and bone density in ambulatory patients and to compare the
      effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy
      on bone density. METHODS: A cross-sectional evaluation was conducted of 71
      patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at
      least 6 months who presented to neurologists at a tertiary referral center. Bone
      mineral density (BMD) as well as serum 25 hydroxy-vitamin D (25-OHD) levels were
      measured. A detailed questionnaire assessing calcium intake as well as previous
      and current intake of antiepileptic medications was administered to all patients.
      RESULTS: Over 50% of adults and children/adolescents had low 25-OHD levels, but
      this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in
      adults. Generalized seizures, duration of epilepsy, and polypharmacy were
      significant determinants of BMD, more so at skeletal sites enriched in cortical
      bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital,
      carbamazepine, and primidone tended to have lower BMD than those on noninducers
      such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and
      ethosuximide. CONCLUSION: Epilepsy and its therapy, including the newer drugs,
      are risk factors for low bone density, irrespective of vitamin D levels. Skeletal
      monitoring with the institution of appropriate therapy is indicated in patients
      on chronic antiepileptic therapy.

PMID- 12011280
TI  - Collagen VI involvement in Ullrich syndrome: a clinical, genetic, and
      immunohistochemical study.
AB  - BACKGROUND: Ullrich congenital muscular dystrophy (UCMD) is a form of merosin
      positive congenital muscular dystrophy characterized by proximal contractures,
      distal laxity, rigidity of the spine, and respiratory complications. Recently, a
      deficiency of collagen VI on muscle and skin biopsy together with recessive
      mutations in the collagen 6A2 gene were reported in three families with UCMD.
      However, the clinical spectrum, frequency, and level of heterogeneity of this
      disorder are not known. SUBJECTS AND METHODS: The authors studied 15 patients
      (aged 3 to 23.6 years) with a clinical diagnosis of UCMD. Linkage analysis to the
      three collagen VI genes was performed in all informative families (n = 7),
      whereas immunohistochemical analysis of collagen VI expression in muscle was
      performed in the remaining cases. RESULTS: An immunocytochemical reduction of
      collagen VI was observed in six patients. Three of the six patients belonged to
      informative families, and haplotype analysis clearly suggested linkage to the
      COL6A1/2 locus in two cases and to the COL6A3 loci in the third case. In the
      remaining nine patients, primary collagen VI involvement was excluded based on
      either the linkage analysis (four families) or considered unlikely based on
      normal immunolabeling of collagen VI. Age and presentation at onset, the
      distribution and severity of weakness and contractures, and the frequency of
      nonambulant patients were similar in the patients with and without collagen VI
      involvement. Distal laxity, rigidity of the spine, scoliosis, failure to thrive,
      and early and severe respiratory impairment were found in all patients by the end
      of the first decade of life, irrespective of their maximum motor functional
      ability or their collagen status. CONCLUSIONS: These results suggest that
      collagen VI involvement is relatively common in UCMD (40%); however, the role of
      this molecule was excluded in a number of cases, suggesting genetic heterogeneity
      of this condition.

PMID- 12011281
TI  - Treatment of spinal epidural metastasis improves patient survival and functional
      state.
AB  - OBJECTIVES: To determine factors affecting the success of radiation therapy (RT)
      of spinal epidural metastases and patient survival after RT. DESIGN/METHODS: One
      hundred thirty-nine male veterans with an initial spinal epidural metastases
      treated with dexamethasone and RT were evaluated prospectively. Patients were
      followed until death. RESULTS: At presentation, 84 patients could walk. After RT,
      119 patients walked. The likelihood of regaining ambulation increased if
      treatment began <12 hours after loss of ambulation and if patients had bladder
      and bowel function and sacral sensory sparing. Treatment reduced pain levels, and
      ambulatory patients had less pain compared with nonambulatory patients. Median
      length of survival was 104 weeks for ambulatory patients and 6 weeks for
      nonambulatory patients. Mean interval between loss of ambulation and death was
      4.0 +/- 0.5 weeks. Recurrent spinal epidural metastases occurred in 8.63% of
      patients. CONCLUSIONS: Patients who walked after treatment lived longer, were
      ambulatory for most of their remaining life, had less pain, and had a lower
      incidence of depression.

PMID- 12011282
TI  - Emergency craniotomy in patients worsening due to expanded cerebral hematoma: to
      what purpose?
AB  - BACKGROUND: Supratentorial intracerebral hematomas often are evacuated in rapidly
      deteriorating patients. Surgery may prevent death but not necessarily disability.
      The authors studied the outcome of emergent clot evacuation in patients with
      worsening massive intracerebral hemorrhage. METHODS: The authors reviewed data on
      26 consecutive, acutely worsening patients with nontraumatic intracerebral
      hemorrhage who had surgery for clot evacuation. All patients had clinical (stupor
      or coma, loss of pontomesencephalic brainstem reflexes, extensor posturing) or
      radiologic (midline shift of septum pellucidum > or =1 cm downward or
      obliteration of the ambient and suprasellar cisterns caused by displacement of
      the temporal uncus) signs of herniation. Outcome was defined using the Glasgow
      Outcome Scale (GOS). RESULTS: Fifty-six percent of patients died (GOS 1), 22%
      remained severely disabled (GOS 3), and 22% regained independence (GOS 4-5).
      Considering findings before surgery, upper brainstem reflexes were preserved more
      often in survivors (66% vs. 14%; p = 0.01). All patients who had a combination of
      absent pupillary, corneal, and oculocephalic reflexes and extensor posturing
      before craniotomy died. No patient lacking corneal or oculocephalic reflexes
      prior to surgery regained functional independence. CONCLUSIONS: Craniotomy for
      rapidly worsening patients with supratentorial intracerebral hemorrhage and
      radiologic signs of brain tissue shift may result in functional independence in
      approximately a quarter of patients. However, all comatose patients who lost
      upper brainstem reflexes and had extensor posturing died despite surgery.

PMID- 12011283
TI  - Patients with progressive multiple sclerosis have elevated antibodies to
      neurofilament subunit.
AB  - OBJECTIVE: The cause of axonal loss, an important contributor to disability in
      MS, is poorly understood. This study investigated whether progression in MS is
      associated with CSF antibodies to the 68-kd light neurofilament subunit (NF-L),
      an axonal cytoskeletal protein, and compared this with antibodies against tubulin
      and the heavy neurofilament subunit (NF-H). METHODS: IgG to NF-L, tubulin, and NF
      H was measured by immunoassay in matched CSF and serum samples from patients with
      relapsing-remitting MS (RRMS; n = 39), primary progressive MS (PPMS; n = 10), and
      secondary progressive MS (SPMS; n = 18); patients with other inflammatory (n =
      21) and noninflammatory (n = 40) neurologic diseases; and healthy controls (n =
      12). Immunocytochemistry was performed to assess antibody binding to human brain
      sections, and isoelectric focusing with immunoblotting was performed to assess
      oligoclonal anti-NF-L production. RESULTS: Intrathecal production of anti-NF-L
      antibodies was significantly elevated in PPMS and SPMS. In contrast, there were
      no significant differences in CSF levels of antibodies to tubulin or NF-H between
      the groups. Anti-NF-L, antitubulin, and anti-NF-H levels correlated with the
      duration of disease before lumbar puncture and Expanded Disability Status Scale
      levels. Immunocytochemistry demonstrated binding of CSF or serum antibodies to
      axonal or neuronal components in six of seven RRMS patients, seven of seven PPMS
      patients, and eight of 10 SPMS patients tested. Isoelectric focusing demonstrated
      independent CSF oligoclonal bands reactive with NF-L in six of 13 specimens
      tested. CONCLUSIONS: Anti-NF-L antibodies seem to be raised in progressive MS and
      may serve as a marker for axonal loss and disease progression. They may
      contribute to axonal loss and the accumulation of disability.

PMID- 12011284
TI  - MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk
      of PD.
AB  - BACKGROUND: A polymorphism (G to A transition) in intron 13 of the mitochondrial
      enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with
      the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity),
      the risk of idiopathic PD. Also, the association between never smoking and PD
      risk may be present only in people with the MAOB G allele. METHODS: The authors
      studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women
      aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men
      aged 40 to 75 in 1986). They identified new PD cases through 1996, selected
      random control subjects matched on age and study cohort, and obtained DNA samples
      from blood or buccal smears from 85% of the eligible cases and 84% of the control
      subjects. They included genotypes from 214 cases and 449 control subjects, all
      Caucasian. RESULTS: The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB
      genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT
      genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for
      those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA
      and COMT(HH). There was a strong association between never smoking and PD risk in
      all groups defined by MAOB and COMT genotypes. CONCLUSION: The findings do not
      support a major role of the MAOB intron 13 polymorphism in the development of PD,
      either by itself or by interacting with smoking.

PMID- 12011285
TI  - Epidural lipomatosis.

PMID- 12011286
TI  - Blood flow responses to deep brain stimulation of thalamus.
AB  - BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) of the ventral
      intermediate nucleus of the thalamus (VIM) provides remarkable relief of tremor
      in the limbs contralateral to the side of the brain stimulated. The benefits have
      been sufficiently dramatic that this is now an accepted clinical treatment of
      essential as well as other forms of tremor. Despite this clinical benefit, the
      mechanism of action of DBS remains unknown. In this investigation, we sought to
      determine the effects of VIM DBS on neuronal function. METHODS: The authors used
      PET measurements of qualitative regional cerebral blood flow in patients with
      essential tremor to determine the effects of DBS in the left VIM. Each subject
      had four to six scans with the arms at rest and DBS turned either on or off
      during alternate scans. Continuous physiologic monitoring revealed no tremor
      during any of the scans. The PET images from each subject were aligned, averaged,
      and coregistered to a standard image oriented in stereotactic space. RESULTS: The
      authors used subtraction image analysis with statistical parametric mapping
      methods and a restricted volume search to identify a significantly increased flow
      response at the site of stimulation in thalamus. An exploratory analysis revealed
      increased flow in ipsilateral supplementary motor area, a region that receives
      afferents from VIM. CONCLUSIONS: The increased blood flow at terminal fields of
      thalamocortical projections suggests that DBS stimulates and does not inactivate
      projection neurons in VIM thalamus.

PMID- 12011287
TI  - Functional vitamin B(12) deficiency and Alzheimer disease.
AB  - Moderately elevated total serum homocysteine is associated with an increased risk
      of atherothrombotic vascular events. Accordingly, serum homocysteine is increased
      in patients with vascular dementia but is also increased in clinically diagnosed
      and histologically confirmed AD. It is generally considered that homocysteine
      potentiates endothelial and neuronal oxidative injury in these diseases. A
      complementary model of oxidative stress-induced hyperhomocystinemia is proposed
      by the authors. The hypothesis accounts for several unusual features relating to
      single-carbon metabolism and AD, including the absence of macrocytic anemia in
      these patients. It is suggested that cerebral oxidative stress augments the
      oxidation of an intermediate form of vitamin B(12) (cob[I]alamin) generated in
      the methionine synthase reaction, thereby impairing the metabolism of
      homocysteine. Oxidative stress also compromises the intraneuronal reduction of
      the vitamin to its metabolically active state. Currently available pharmaceutic
      forms of vitamin B(12) are unlikely to be utilized by neurons under these
      conditions. Glutathionylcobalamin might be preferential for the treatment of such
      patients.

PMID- 12011288
TI  - Giant cell arteritis causing multiple vertebro-basilar infarcts.

PMID- 12011289
TI  - Jules Cotard (1840-1889): his life and the unique syndrome which bears his name.
AB  - Dr. Jules Cotard (1840-1889) was a Parisian neurologist who first described the
      delire des negations. Cotard's syndrome or Cotard's delusion comprises any one of
      a series of delusions ranging from the fixed and unshakable belief that one has
      lost organs, blood, or body parts to believing that one has lost one's soul or is
      dead. In its most profound form, the delusion takes the form of a professed
      belief that one does not exist. Encountered primarily in psychoses such as
      schizophrenia and bipolar disorder, Cotard's syndrome has also been described in
      organic lesions of the nondominant temporoparietal cortex as well as in migraine.
      Cotard's delusion is the only self-certifiable syndrome of delusional psychosis.
      Jules Cotard, a Parisian neurologist and psychiatrist and former military
      surgeon, was one of the first to induce cerebral atrophy by the experimental
      embolization of cerebral arteries in animals and a pioneer in studies of the
      clinicopathologic correlates of cerebral atrophy secondary to perinatal and
      postnatal pathologic changes. He was the first to record that unilateral cerebral
      atrophy in infancy does not necessarily lead to aphasia and was also the pioneer
      of studies of altered conscious states in diabetic hyperglycemia.

PMID- 12011290
TI  - Safety, tolerability, and efficacy of orally administered cannabinoids in MS.
AB  - The authors conducted a randomized, double-blind, placebo-controlled, twofold
      crossover study in 16 patients with MS who presented with severe spasticity to
      investigate safety, tolerability, and efficacy of oral Delta(9)
      Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were
      safe, but adverse events were more common with plant-extract treatment. Compared
      with placebo, neither THC nor plant-extract treatment reduced spasticity. Both
      THC and plant-extract treatment worsened the participant's global impression.

PMID- 12011291
TI  - Prevalence and incidence of cluster headache in the Republic of San Marino.
AB  - Based on a preceding survey performed in 1985, the authors estimated the
      prevalence and incidence of cluster headache (CH) in the Republic of San Marino
      (26,628 inhabitants at 31 December 1999). All cases were diagnosed by direct
      interview according to International Headache Society criteria. The prevalence
      rate was 56/100,000 (95% CI 31.3 to 92.4), and the incidence rate was
      2.5/100,000/year (95% CI 1.14 to 4.75). Most cases showed rare clusters. This is
      the first prospective study on the incidence of CH.

PMID- 12011292
TI  - A one-year study on the pharmacodynamic profile of interferon-beta1a in MS.
AB  - Interferon (IFN)-beta1a induction of neopterin and beta2-microglobulin (beta2-MG)
      were evaluated over 1 year in patients with MS. Neopterin and beta2-MG levels
      peaked 24 to 48 hours after weekly injections of IFNbeta1a over the entire study
      period. Predose levels of neopterin decreased significantly, consistent with a
      long-term decrease in IFNgamma expression and macrophage activation during
      IFNbeta-1a treatment. Predose levels of beta2-MG increased, the significance of
      which is as yet unclear.

PMID- 12011293
TI  - Isolated hand palsy due to cortical infarction: localization of the motor hand
      area.
AB  - The authors investigated the lesions and symptoms of five patients who presented
      with monoparesis of an upper limb due to cortical infarction. The location of the
      cortical motor hand area seems to be in the middle to lower portion of the
      anterior wall of the central sulcus. Severity of finger paralysis associated with
      impairment of this area varied in different fingers and occurred in two patterns:
      one variant predominantly affected the radial side, and the other predominantly
      affected the ulnar side.

PMID- 12011294
TI  - Cheiro-oral syndrome due to a midbrain lesion.

PMID- 12011295
TI  - Prednisolone (30-60 mg/day) for diseases other than AD decreases amyloid beta
      peptides in CSF.
AB  - The effect of corticosteroid on the concentration of amyloid beta-peptide (Abeta)
      in human CSF obtained from 16 patients without dementia treated with prednisolone
      (> or =30 mg daily) was studied. The concentrations of Abetax-40 and Abetax-42 in
      CSF decreased after treatment was started (p < 0.002). A moderate- or high-dose
      regimen of prednisolone decreases Abeta production or increases Abeta degradation
      in the human brain and deserves further study in AD.

PMID- 12011296
TI  - Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics.
AB  - The authors studied the pharmacokinetics of levodopa (LD) with and without
      pramipexole (PPX) in men and postmenopausal women with PD. Patients on stable
      dose of carbidopa/LD were randomized to receive escalating doses of placebo or
      PPX over 7 weeks. LD and PPX pharmacokinetics were performed after a single test
      dose 25/100 of carbidopa/LD, before initiation of PPX or placebo, at 1.5 mg/d and
      4.5 mg/d of PPX or placebo. Compared to men, women had greater LD
      bioavailability. PPX did not alter LD bioavailability, and PPX pharmacokinetics
      were equivalent in men and women.

PMID- 12011297
TI  - High age-adjusted prevalence of Parkinson's disease among Inuits in Greenland.
AB  - The prevalence of PD among Inuits in Greenland has not been determined. The
      authors found 40 patients with PD at the prevalence date January 1, 2000. The
      crude prevalence of PD was estimated to be 81.0 per 100.000 inhabitants born in
      Greenland. However, owing to the low proportion of 50+ year old Inuits (16.5 vs
      33.5% in Denmark) the age-adjusted prevalence was much higher-187.5 per 100,000
      persons.

PMID- 12011298
TI  - MRI during postangiography headache.

PMID- 12011299
TI  - Generalized epilepsy with febrile seizures plus: mutation of the sodium channel
      subunit SCN1B.
AB  - Generalized epilepsy with febrile seizures plus (GEFS(+)) is an important
      childhood genetic epilepsy syndrome with heterogeneous phenotypes, including
      febrile seizures (FS) and generalized epilepsies of variable severity. Forty
      unrelated GEFS(+) and FS patients were screened for mutations in the sodium
      channel beta-subunits SCN1B and SCN2B, and the second GEFS(+) family with an
      SCN1B mutation is described here. The family had 19 affected individuals: 16 with
      typical GEFS(+) phenotypes and three with other epilepsy phenotypes. Site
      specific mutation within SCN1B remains a rare cause of GEFS(+), and the authors
      found no evidence to implicate SCN2B in this syndrome.

PMID- 12011300
TI  - Familial temporal lobe epilepsy with febrile seizures.
AB  - Described are the clinical, EEG, MR, and genetic characteristics of 106 members
      of a family with autosomal dominant temporal lobe epilepsy (TLE) and febrile
      seizures (FS), with 22 affected individuals. Eleven patients had a history of FS,
      and 10 patients had TLE. EEG showed epileptic activity in five. None had
      hippocampal sclerosis. There was no evidence for linkage to 13 candidate loci.
      This large family with autosomal dominant TLE has a distinct phenotype and shows
      no linkage to known candidate regions for familial partial epilepsy and FS.

PMID- 12011301
TI  - Vertebral artery dissection and stroke following neck manipulation by Native
      American healer.

PMID- 12011302
TI  - Absence of elevated anti-alpha-synuclein and anti-EBV latent membrane protein
      antibodies in PD.

PMID- 12011303
TI  - Mifepristone (RU 486) for Alzheimer's disease.

PMID- 12011304
TI  - Guillain-Barre syndrome presenting with loss of taste.

PMID- 12011305
TI  - Increased glutamate in CSF and plasma of patients with HIV dementia.

PMID- 12011306
TI  - Glatiramer acetate reduces the proportion of new MS lesions evolving into "black
      holes".

PMID- 12011307
TI  - Head circumference and incident Alzheimer's disease: modification by
      apolipoprotein E.

PMID- 12011308
TI  - High-grade carotid stenosis detected before general surgery: is endarterectomy
      indicated?

PMID- 12011309
TI  - Clinical features of withdrawal headache following overuse of triptans and other
      headache drugs.

PMID- 12011310
TI  - Rapid infusion of intravenous immunoglobulin in patients with neuromuscular
      diseases.

PMID- 12011329
TI  - Developmental expression of functional cyclooxygenases in zebrafish.
AB  - Study of the cyclooxygenases (COXs) has been limited by the role of COX-2 in
      murine reproduction and renal organogenesis. We sought to characterize COX
      expression and function in zebrafish (z). Full-length cDNAs of zCOX-1 and zCOX-2
      were cloned and assigned to conserved regions of chromosomes 5 and 2,
      respectively. The deduced proteins are 67% homologous with their human orthologs.
      Prostaglandin (PG) E(2) is the predominant zCOX product detected by mass
      spectrometry. Pharmacological inhibitors demonstrate selectivity when directed
      against heterologously expressed zCOX isoforms. Zebrafish thrombocyte aggregation
      ex vivo and hemostasis in vivo are sensitive to inhibition of zCOX-1, but not
      zCOX-2. Both zCOXs were widely expressed during development, and knockdown of
      zCOX-1 causes growth arrest during early embryogenesis. zCOX-1 is widely evident
      in the embryonic vasculature, whereas zCOX-2 exhibits a more restricted pattern
      of expression. Both zCOX isoforms are genetically and functionally homologous to
      their mammalian orthologs. The zebrafish affords a tractable model system for the
      study of COX biology and development.

PMID- 12011331
TI  - How I started in science.

PMID- 12011332
TI  - Stable chloroplast transformation of the unicellular red alga Porphyridium
      species.
AB  - Red algae are extremely attractive for biotechnology because they synthesize
      accessory photosynthetic pigments (phycobilins and carotenoids), unsaturated
      fatty acids, and unique cell wall sulfated polysaccharides. We report a high
      efficiency chloroplast transformation system for the unicellular red microalga
      Porphyridium sp. This is the first genetic transformation system for Rhodophytes
      and is based on use of a mutant form of the gene encoding acetohydroxyacid
      synthase [AHAS(W492S)] as a dominant selectable marker. AHAS is the target enzyme
      of the herbicide sulfometuron methyl, which effectively inhibits growth of
      bacteria, fungi, plants, and algae. Biolistic transformation of synchronized
      Porphyridium sp. cells with the mutant AHAS(W492S) gene that confers herbicide
      resistance gave a high frequency of sulfomethuron methyl-resistant colonies. The
      mutant AHAS gene integrated into the chloroplast genome by homologous
      recombination. This system paves the way for expression of foreign genes in red
      algae and has important biotechnological implications.

PMID- 12011334
TI  - Cytometrical evidence that the loss of seed weight in the miniature1 seed mutant
      of maize is associated with reduced mitotic activity in the developing endosperm.

PMID- 12011333
TI  - Agrobacterium tumefaciens-mediated transformation of maize embryos using a
      standard binary vector system.
AB  - We have achieved routine transformation of maize (Zea mays) using an
      Agrobacterium tumefaciens standard binary (non-super binary) vector system.
      Immature zygotic embryos of the hybrid line Hi II were infected with A.
      tumefaciens strain EHA101 harboring a standard binary vector and cocultivated in
      the presence of 400 mg L-1 L-cysteine. Inclusion of L-cysteine in cocultivation
      medium lead to an improvement in transient beta-glucuronidase expression observed
      in targeted cells and a significant increase in stable transformation efficiency,
      but was associated with a decrease in embryo response after cocultivation. The
      average stable transformation efficiency (no. of bialaphos-resistant events
      recovered per 100 embryos infected) of the present protocol was 5.5%. Southern
      blot and progeny analyses confirmed the integration, expression, and inheritance
      of the bar and gus transgenes in R0, R1, and R2 generations of transgenic events.
      To our knowledge, this represents the first report in which fertile, stable
      transgenic maize has been routinely produced using an A. tumefaciens standard
      binary vector system.

PMID- 12011335
TI  - Maintenance of shoot and floral meristem cell proliferation and fate.

PMID- 12011336
TI  - Heterochromatin in animals and plants. Similarities and differences.

PMID- 12011337
TI  - Adaptation of H+-pumping and plasma membrane H+ ATPase activity in proteoid roots
      of white lupin under phosphate deficiency.
AB  - White lupin (Lupinus albus) is able to adapt to phosphorus deficiency by
      producing proteoid roots that release a huge amount of organic acids, resulting
      in mobilization of sparingly soluble soil phosphate in rhizosphere. The
      mechanisms responsible for the release of organic acids by proteoid root cells,
      especially the trans-membrane transport processes, have not been elucidated.
      Because of high cytosolic pH, the release of undissociated organic acids is not
      probable. In the present study, we focused on H+ export by plasma membrane H+
      ATPase in active proteoid roots. In vivo, rhizosphere acidification of active
      proteoid roots was vanadate sensitive. Plasma membranes were isolated from
      proteoid roots and lateral roots from P-deficient and -sufficient plants. In
      vitro, in comparison with two types of lateral roots and proteoid roots of P
      sufficient plants, the following increase of the various parameters was induced
      in active proteoid roots of P-deficient plants: (a) hydrolytic ATPase activity,
      (b) Vmax and Km, (c) H+ ATPase enzyme concentration of plasma membrane, (d) H+
      pumping activity, (e) pH gradient across the membrane of plasmalemma vesicles,
      and (f) passive H+ permeability of plasma membrane. In addition, lower vanadate
      sensitivity and more acidic pH optimum were determined for plasma membrane ATPase
      of active proteoid roots. Our data support the hypothesis that in active proteoid
      root cells, H+ and organic anions are exported separately, and that modification
      of plasma membrane H+ ATPase is essential for enhanced rhizosphere acidification
      by active proteoid roots.

PMID- 12011338
TI  - An ultraviolet-B-resistant mutant with enhanced DNA repair in Arabidopsis.
AB  - An ultraviolet-B (UV-B)-resistant mutant, uvi1 (UV-B insensitive 1), of
      Arabidopsis was isolated from 1,280 M(1) seeds that had been exposed to ion beam
      irradiation. The fresh weight of uvi1 under high-UV-B exposure was more than
      twice that of the wild type. A root-bending assay indicated that root growth was
      less inhibited by UV-B exposure in uvi1 than in the wild type. When the seedlings
      were grown under white light, the UV-B dose required for 50% inhibition was about
      6 kJ m(-2) for the wild type and 9 kJ m(-2) for uvi1. When the seedlings were
      irradiated with UV-B in darkness, the dose required for 50% inhibition was about
      1.5 kJ m(-2) for the wild type and 4 kJ m(-2) for uvi1. An enzyme-linked
      immunosorbent assay showed that the reduction in levels of cyclobutane pyrimidine
      dimers (CPDs) under white light and of (6-4) photoproducts in darkness occurred
      faster in uvi1 than in the wild type. These results indicate that uvi1 had
      increased photoreactivation of CPDs and dark repair of (6-4) photoproducts,
      leading to strong UV-B resistance. Furthermore, the transcript levels of PHR1
      (CPD photolyase gene) were much higher in uvi1 than in the wild type both under
      white light and after UV-B exposure. Placing the plants in the dark before UV-B
      exposure decreases the early reduction of CPDs in the wild type but not in uvi1.
      Our results suggest that UVI1 is a negative regulator of two independent DNA
      repair systems.

PMID- 12011339
TI  - Tissue localization of a submergence-induced 1-aminocyclopropane-1-carboxylic
      acid synthase in rice.
AB  - At least two 1-aminocyclopropane-1-carboxylic acid synthase genes (ACS) are
      implicated in the submergence response of rice (Oryza sativa). Previously, the OS
      ACS5 gene has been shown to be induced during short- as well as long-term
      complete submergence of seedlings and to be controlled by a balance of
      gibberellin and abscisic acid in both lowland and deepwater rice. This study
      demonstrates that OS-ACS5 mRNA is localized in specific tissues and cells both
      during normal development and in response to complete submergence. The temporal
      and spatial regulation of OS-ACS5 expression is presented by in situ
      hybridization and histochemical analysis of beta-glucuronidase (GUS) activity in
      transgenic rice carrying an OS-ACS5-gus fusion. Whole-mount in situ hybridization
      revealed that in air-grown rice seedlings, OS-ACS5 was expressed at a low level
      in the shoot apex, meristems, leaf, and adventitious root primordia, and in
      vascular tissues of nonelongated stems and leaf sheaths. In response to complete
      submergence, the expression in vascular bundles of young stems and leaf sheaths
      was strongly induced. The results of histochemical GUS assays were consistent
      with those found by whole-mount in situ hybridization. Our findings suggest that
      OS-ACS5 plays a role in vegetative growth of rice under normal conditions and is
      also recruited for enhanced growth upon complete submergence. The possible
      implication of OS-ACS5 in root-shoot communication during submergence stress and
      its putative role in aerenchyma formation upon low-oxygen stress are discussed.

PMID- 12011340
TI  - Characterization of FRO1, a pea ferric-chelate reductase involved in root iron
      acquisition.
AB  - To acquire iron, many plant species reduce soil Fe(III) to Fe(II) by Fe(III)
      chelate reductases embedded in the plasma membrane of root epidermal cells. The
      reduced product is then taken up by Fe(II) transporter proteins. These activities
      are induced under Fe deficiency. We describe here the FRO1 gene from pea (Pisum
      sativum), which encodes an Fe(III)-chelate reductase. Consistent with this
      proposed role, FRO1 shows similarity to other oxidoreductase proteins, and
      expression of FRO1 in yeast conferred increased Fe(III)-chelate reductase
      activity. Furthermore, FRO1 mRNA levels in plants correlated with Fe(III)-chelate
      reductase activity. Sites of FRO1 expression in roots, leaves, and nodules were
      determined. FRO1 mRNA was detected throughout the root, but was most abundant in
      the outer epidermal cells. Expression was detected in mesophyll cells in leaves.
      In root nodules, mRNA was detected in the infection zone and nitrogen-fixing
      region. These results indicate that FRO1 acts in root Fe uptake and they suggest
      a role in Fe distribution throughout the plant. Characterization of FRO1 has also
      provided new insights into the regulation of Fe uptake. FRO1 expression and
      reductase activity was detected only in Fe-deficient roots of Sparkle, whereas
      both were constitutive in brz and dgl, two mutants with incorrectly regulated Fe
      accumulation. In contrast, FRO1 expression was responsive to Fe status in shoots
      of all three plant lines. These results indicate differential regulation of FRO1
      in roots and shoots, and improper FRO1 regulation in response to a shoot-derived
      signal of iron status in the roots of the brz and dgl mutants.

PMID- 12011341
TI  - Direct interference with rhamnogalacturonan I biosynthesis in Golgi vesicles.
AB  - Pectin is a class of complex cell wall polysaccharides with multiple roles during
      cell development. Assigning specific functions to particular polysaccharides is
      in its infancy, in part, because of the limited number of mutants and
      transformants available with modified pectic polymers in their walls. Pectins are
      also important polymers with diverse applications in the food and pharmaceutical
      industries, which would benefit from technology for producing pectins with
      specific functional properties. In this report, we describe the generation of
      potato (Solanum tuberosum L. cv Posmo) tuber transformants producing pectic
      rhamnogalacturonan I (RGI) with a low level of arabinosylation. This was achieved
      by the expression of a Golgi membrane-anchored endo-alpha-1,5-arabinanase. Sugar
      composition analysis of RGI isolated from transformed and wild-type tubers showed
      that the arabinose content was decreased by approximately 70% in transformed cell
      walls compared with wild type. The modification of the RGI was confirmed by
      immunolabeling with an antibody recognizing alpha-1,5-arabinan. This is the first
      time, to our knowledge, that the biosynthesis of a plant cell wall polysaccharide
      has been manipulated through the action of a glycosyl hydrolase targeted to the
      Golgi compartment.

PMID- 12011342
TI  - Phospholipase A2 activity triggers the wound-activated chemical defense in the
      diatom Thalassiosira rotula.
AB  - The activation of oxylipin-based chemical defense in the diatom Thalassiosira
      rotula is initiated by phospholipases that act immediately after cell damage.
      This lipase activity is responsible for the preferential release of free mono-
      and polyunsaturated fatty acids. Among these, eicosatetraenoic- and
      eicosapentaenoic acid are further converted by lipoxygenases to reactive
      defensive metabolites such as the antiproliferative alpha,beta,gamma,delta
      unsaturated aldehydes 2,4-decadienal and 2,4,7-decatrienal. We show that mainly
      saturated free fatty acids are present in the intact diatom T. rotula, whereas
      the amount of free polyunsaturated eicosanoids is drastically increased in the
      first minutes after wounding. Using fluorescent probes, the main enzyme activity
      responsible for initiation of the aldehyde-generating
      lipase/lipoxygenase/hydroperoxide lyase cascade was characterized as a
      phospholipase A2. All enzymes involved in this specific defensive reaction are
      active in seawater over several minutes. Thus, the mechanism allows the
      unicellular algae to overcome restrictions arising out of potential dilution of
      defensive metabolites. Only upon predation are high local concentrations of
      aldehydes formed in the vicinity of the herbivores, whereas in times of low
      stress, cellular resources can be invested in the formation of eicosanoid-rich
      phospholipids. In contrast to higher plants, which use lipases acting on
      galactolipids to release C18 fatty acids for production of leaf-volatile
      aldehydes, diatoms rely on phospholipids and the transformation of C20 fatty
      acids to form 2,4-decadienal and 2,4,7-decatrienal as an activated defense.

PMID- 12011343
TI  - A large population of small chloroplasts in tobacco leaf cells allows more
      effective chloroplast movement than a few enlarged chloroplasts.
AB  - We generated transgenic tobacco (Nicotiana tabacum cv Xanthi) plants that
      contained only one to three enlarged chloroplasts per leaf mesophyll cell by
      introducing NtFtsZ1-2, a cDNA for plastid division. These plants were used to
      investigate the advantages of having a large population of small chloroplasts
      rather than a few enlarged chloroplasts in a leaf mesophyll cell. Despite the
      similarities in photosynthetic components and ultrastructure of photosynthetic
      machinery between wild-type and transgenic plants, the overall growth of
      transgenic plants under low- and high-light conditions was retarded. In wild-type
      plants, the chloroplasts moved toward the face position under low light and
      toward the profile position under high-light conditions. However, chloroplast
      rearrangement in transgenic plants in response to light conditions was not
      evident. In addition, transgenic plant leaves showed greatly diminished changes
      in leaf transmittance values under both light conditions, indicating that
      chloroplast rearrangement was severely retarded. Therefore, under low-light
      conditions the incomplete face position of the enlarged chloroplasts results in
      decreased absorbance of light energy. This, in turn, reduces plant growth. Under
      high-light conditions, the amount of absorbed light exceeds the photosynthetic
      utilization capacity due to the incomplete profile position of the enlarged
      chloroplasts, resulting in photodamage to the photosynthetic machinery, and
      decreased growth. The presence of a large number of small and/or rapidly moving
      chloroplasts in the cells of higher land plants permits more effective
      chloroplast phototaxis and, hence, allows more efficient utilization of low
      incident photon flux densities. The photosynthetic apparatus is, consequently,
      protected from damage under high-incident photon flux densities.

PMID- 12011344
TI  - Overexpression of polygalacturonase in transgenic apple trees leads to a range of
      novel phenotypes involving changes in cell adhesion.
AB  - Polygalacturonases (PGs) cleave runs of unesterified GalUA that form
      homogalacturonan regions along the backbone of pectin. Homogalacturonan-rich
      pectin is commonly found in the middle lamella region of the wall where two
      adjacent cells abut and its integrity is important for cell adhesion. Transgenic
      apple (Malus domestica Borkh. cv Royal Gala) trees were produced that contained
      additional copies of a fruit-specific apple PG gene under a constitutive
      promoter. In contrast to previous studies in transgenic tobacco (Nicotiana
      tabacum) where PG overexpression had no effect on the plant (K.W. Osteryoung, K.
      Toenjes, B. Hall, V. Winkler, A.B. Bennett [1990] Plant Cell 2: 1239-1248), PG
      overexpression in transgenic apple led to a range of novel phenotypes. These
      phenotypes included silvery colored leaves and premature leaf shedding due to
      reduced cell adhesion in leaf abscission zones. Mature leaves had malformed and
      malfunctioning stomata that perturbed water relations and contributed to a
      brittle leaf phenotype. Chemical and ultrastructural analyses were used to relate
      the phenotypic changes to pectin changes in the leaf cell walls. The modification
      of apple trees by a single PG gene has offered a new and unexpected perspective
      on the role of pectin and cell wall adhesion in leaf morphology and stomatal
      development.

PMID- 12011345
TI  - Isolation and characterization of two germacrene A synthase cDNA clones from
      chicory.
AB  - Chicory (Cichorium intybus) sesquiterpene lactones were recently shown to be
      derived from a common sesquiterpene intermediate, (+)-germacrene A. Germacrene A
      is of interest because of its key role in sesquiterpene lactone biosynthesis and
      because it is an enzyme-bound intermediate in the biosynthesis of a number of
      phytoalexins. Using polymerase chain reaction with degenerate primers, we have
      isolated two sesquiterpene synthases from chicory that exhibited 72% amino acid
      identity. Heterologous expression of the genes in Escherichia coli has shown that
      they both catalyze exclusively the formation of (+)-germacrene A, making this the
      first report, to our knowledge, on the isolation of (+)-germacrene A synthase
      (GAS)-encoding genes. Northern analysis demonstrated that both genes were
      expressed in all chicory tissues tested albeit at varying levels. Protein
      isolation and partial purification from chicory heads demonstrated the presence
      of two GAS proteins. On MonoQ, these proteins co-eluted with the two
      heterologously produced proteins. The K(m) value, pH optimum, and MonoQ elution
      volume of one of the proteins produced in E. coli were similar to the values
      reported for the GAS protein that was recently purified from chicory roots.
      Finally, the two deduced amino acid sequences were modeled, and the resulting
      protein models were compared with the crystal structure of tobacco (Nicotiana
      tabacum) 5-epi-aristolochene synthase, which forms germacrene A as an enzyme
      bound intermediate en route to 5-epi-aristolochene. The possible involvement of a
      number of amino acids in sesquiterpene synthase product specificity is discussed.

PMID- 12011346
TI  - Laccase down-regulation causes alterations in phenolic metabolism and cell wall
      structure in poplar.
AB  - Laccases are encoded by multigene families in plants. Previously, we reported the
      cloning and characterization of five divergent laccase genes from poplar (Populus
      trichocarpa) xylem. To investigate the role of individual laccase genes in plant
      development, and more particularly in lignification, three independent
      populations of antisense poplar plants, lac3AS, lac90AS, and lac110AS with
      significantly reduced levels of laccase expression were generated. A repression
      of laccase gene expression had no effect on overall growth and development.
      Moreover, neither lignin content nor composition was significantly altered as a
      result of laccase suppression. However, one of the transgenic populations,
      lac3AS, exhibited a 2- to 3-fold increase in total soluble phenolic content. As
      indicated by toluidine blue staining, these phenolics preferentially accumulate
      in xylem ray parenchyma cells. In addition, light and electron microscopic
      observations of lac3AS stems indicated that lac3 gene suppression led to a
      dramatic alteration of xylem fiber cell walls. Individual fiber cells were
      severely deformed, exhibiting modifications in fluorescence emission at the
      primary wall/middle lamella region and frequent sites of cell wall detachment.
      Although a direct correlation between laccase gene expression and lignification
      could not be assigned, we show that the gene product of lac3 is essential for
      normal cell wall structure and integrity in xylem fibers. lac3AS plants provide a
      unique opportunity to explore laccase function in plants.

PMID- 12011347
TI  - LeCPK1, a calcium-dependent protein kinase from tomato. Plasma membrane targeting
      and biochemical characterization.
AB  - The cDNA of LeCPK1, a calcium-dependent protein kinase, was cloned from tomato
      (Lycopersicon esculentum Mill.). LeCPK1 was expressed in Escherichia coli and
      purified from bacterial extracts. The recombinant protein was shown to be a
      functional protein kinase using a synthetic peptide as the substrate (syntide-2,
      Km = 85 microM). Autophosphorylation of LeCPK1 was observed on threonine and
      serine residues, one of which was identified as serine-439. Kinase activity was
      shown to be Ca2+ dependent and required the C-terminal, calmodulin-like domain of
      LeCPK1. Two classes of high- and low-affinity Ca2+-binding sites were observed,
      exhibiting dissociation constants of 0.6 and 55 microM, respectively. LeCPK1 was
      found to phosphorylate the regulatory C-terminal domain of the plasma membrane H+
      ATPase in vitro. A potential role in the regulation of proton pump activity is
      corroborated by the apparent colocalization of the plasma membrane H+-ATPase and
      LeCPK1 in vivo. Upon transient expression in suspension-cultured cells, a C
      terminal fusion of LeCPK1 with the green fluorescent protein was targeted to the
      plasma membrane. Myristoylation of the LeCPK1 N terminus was found to be required
      for plasma membrane targeting.

PMID- 12011348
TI  - A plant gene up-regulated at rust infection sites.
AB  - Expression of the fis1 gene from flax (Linum usitatissimum) is induced by a
      compatible rust (Melampsora lini) infection. Infection of transgenic plants
      containing a beta-glucuronidase (GUS) reporter gene under the control of the fis1
      promoter showed that induction is highly localized to those leaf mesophyll cells
      within and immediately surrounding rust infection sites. The level of induction
      reflects the extent of fungal growth. In a strong resistance reaction, such as
      the hypersensitive fleck mediated by the L6 resistance gene, there is very little
      fungal growth and a microscopic level of GUS expression. Partially resistant flax
      leaves show levels of GUS expression that were intermediate to the level observed
      in the fully susceptible infection. Sequence and deletion analysis using both
      transient Agrobacterium tumefaciens expression and stable transformation assays
      have shown that the rust-inducible fis1 promoter is contained within a 580-bp
      fragment. Homologs of fis1 were identified in expressed sequence tag databases of
      a range of plant species including dicots, monocots, and a gymnosperm. Homologous
      genes isolated from maize (Zea mays; mis1), barley (Hordeum vulgare; bis1), wheat
      (Triticum aestivum; wis1), and Arabidopsis encode proteins that are highly
      similar (76%-82%) to the FIS1 protein. The Arabidopsis homologue has been
      reported to encode a delta1-pyrroline-5-carboxylate dehydrogenase that is
      involved in the catabolism of proline to glutamate. RNA-blot analysis showed that
      mis1 in maize and the bis1 homolog in barley are both up-regulated by a
      compatible infection with the corresponding species-specific rust. The rust
      induced genes homologous to fis1 are present in many plants. The promoters of
      these genes have potential roles for the engineering of synthetic rust resistance
      genes by targeting transgene expression to the sites of rust infection.

PMID- 12011349
TI  - Mutants at the Slender1 locus of barley cv Himalaya. Molecular and physiological
      characterization.
AB  - A dominant dwarf mutant of barley (Hordeum vulgare) that resembles dominant
      gibberellin (GA) "-insensitive" or "-nonresponsive" mutants in other species is
      described. alpha-Amylase production by endosperm half-grains of the mutant
      required GA3 at concentrations about 100 times that of the WT. The mutant showed
      only a slight growth response to GA3, even at very high concentrations. However,
      when additionally dwarfed, growth rate responded to GA3 over the normal
      concentration range, although only back to the original (dwarf) elongation rate.
      Genetic studies indicated that the dominant dwarf locus was either closely linked
      or identical to the Sln1 (Slender1) locus. A barley sequence related to
      Arabidopsis GAI/RGA was isolated, and shown to represent the Sln1 locus by the
      analysis of sln1 mutants. The dominant dwarf mutant was also altered in this
      sequence, indicating that it too is an allele at Sln1. Thus, mutations at Sln1
      generate plants of radically different phenotypes; either dwarfs that are largely
      dominant and GA "-insensitive/-nonresponsive," or the recessive slender types in
      which GA responses appear to be constitutive. Immunoblotting studies showed that
      in growing leaves, SLN1 protein localized almost exclusively to the leaf
      elongation zone. In mutants at the Sln1 locus, there were differences in both the
      abundance and distribution of SLN1 protein, and large changes in the amounts of
      bioactive GAs, and of their metabolic precursors and catabolites. These results
      suggest that there are dynamic interactions between SLN1 protein and GA content
      in determining leaf elongation rate.

PMID- 12011350
TI  - Gibberellin signaling in barley aleurone cells. Control of SLN1 and GAMYB
      expression.
AB  - We have previously identified GAMYB, a gibberellin (GA)-regulated transcriptional
      activator of alpha-amylase gene expression, in aleurone cells of barley (Hordeum
      vulgare). To examine the regulation of GAMYB expression, we describe the use of
      nuclear run-on experiments to show that GA causes a 2-fold increase in the rate
      of GAMYB transcription and that the effect of GA can be blocked by abscisic acid
      (ABA). To identify GA-signaling components that regulate GAMYB expression, we
      examined the role of SLN1, a negative regulator of GA signaling in barley. SLN1,
      which is the product of the Sln1 (Slender1) locus, is necessary for repression of
      GAMYB in barley aleurone cells. The activity of SLN1 in aleurone cells is
      regulated posttranslationally. SLN1 protein levels decline rapidly in response to
      GA before any increase in GAMYB levels. Green fluorescent protein-SLN1 fusion
      protein was targeted to the nucleus of aleurone protoplasts and disappeared in
      response to GA. Evidence from a dominant dwarf mutant at Sln1, and from the gse1
      mutant (that affects GA "sensitivity"), indicates that GA acts by regulating SLN1
      degradation and not translation. Mutation of the DELLA region of SLN1 results in
      increased protein stability in GA-treated layers, indicating that the DELLA
      region plays an important role in GA-induced degradation of SLN1. Unlike GA, ABA
      had no effect on SLN1 stability, confirming that ABA acts downstream of SLN1 to
      block GA signaling.

PMID- 12011351
TI  - Gibberellin produced in the cotyledon is required for cell division during tissue
      reunion in the cortex of cut cucumber and tomato hypocotyls.
AB  - Cucumber (Cucumis sativus) hypocotyls were cut to one-half of their diameter
      transversely, and morphological and histochemical analyses of the process of
      tissue reunion in the cortex were performed. Cell division in the cortex
      commenced 3 d after cutting, and the cortex was nearly fully united within 7 d.
      4',6-Diamidino-2-phenylindole staining and 5-bromo-2'-deoxyuridine labeling
      experiments indicate that nDNA synthesis occurred during this process. In
      addition, specific accumulation of pectic substances was observed in the cell
      wall of attached cells in the reunion region of the cortex. Cell division during
      tissue reunion was strongly inhibited when the cotyledon was removed. This
      inhibition was reversed by applying gibberellin (GA, 10(-4) M GA3) to the apical
      tip of the cotyledon-less plant. Supporting this observation, cell division in
      the cortex was inhibited by treatment of the cotyledon with 10(-4) M uniconazole
      P (an inhibitor of GA biosynthesis), and this inhibition was also reversed by
      simultaneous application of GA. In contrast to the essential role of cotyledon,
      normal tissue reunion in cut hypocotyls was still observed when the shoot apex
      was removed. The requirement of GA for tissue reunion in cut hypocotyls was also
      evident in the GA-deficient gib-1 mutant of tomato (Lycopersicon esculentum). Our
      results suggest that GA, possibly produced in cotyledons, is essential for cell
      division in reuniting cortex of cut hypocotyls.

PMID- 12011352
TI  - Structure-function analysis of nod factor-induced root hair calcium spiking in
      Rhizobium-legume symbiosis.
AB  - In the Rhizobium-legume symbiosis, compatible bacteria and host plants interact
      through an exchange of signals: Host compounds promote the expression of
      bacterial biosynthetic nod (nodulation) genes leading to the production of a
      lipochito-oligosaccharide signal, the Nod factor (NF). The particular array of
      nod genes carried by a given species of Rhizobium determines the NF structure
      synthesized and defines the range of legume hosts by which the bacterium is
      recognized. Purified NF can induce early host responses even in the absence of
      live Rhizobium One of the earliest known host responses to NF is an oscillatory
      behavior of cytoplasmic calcium, or calcium spiking, in root hair cells,
      initially observed in Medicago spp. and subsequently characterized in four other
      genera (D.W. Ehrhardt, R. Wais, S.R. Long [1996] Cell 85: 673-681; S.A. Walker,
      V. Viprey, J.A. Downie [2000] Proc Natl Acad Sci USA 97: 13413-13418; D.W.
      Ehrhardt, J.A. Downie, J. Harris, R.J. Wais, and S.R. Long, unpublished data). We
      sought to determine whether live Rhizobium trigger a rapid calcium spiking
      response and whether this response is NF dependent. We show that, in the
      Sinorhizobium meliloti-Medicago truncatula interaction, bacteria elicit a calcium
      spiking response that is indistinguishable from the response to purified NF. We
      determine that calcium spiking is a nod gene-dependent host response. Studies of
      calcium spiking in M. truncatula and alfalfa (Medicago sativa) also uncovered the
      possibility of differences in early NF signal transduction. We further
      demonstrate the sufficiency of the nod genes for inducing calcium spiking by
      using Escherichia coli BL21 (DE3) engineered to express 11 S. meliloti nod genes.